Volume 20, Issue 1

Objectives This study aims to assess the potential mechanism of rutin to treat triple-negative breast cancer (TNBC) based on network pharmacology followed by in vitro experiments. Methods The potential rutin targets were predicted, and the DisGeNET database was used to obtain the disease targets. The intersection targets were identified with Venny 2.1 software, with the String database subsequently used as input to produce the “drug-target-disease” visual network employing Cytoscape 3.7.2. Gene ontology. Kyoto Encyclopaedia of Genes and Genomes analyses were performed for intersection targets, while AutoDock Vina was used for molecular docking and visualization. Cell viability was assessed using the Colorimetric CCK-8 test, and apoptosis was analyzed using PI/Annexin V. The predicted core targets were confirmed by qPCR and western blotting assays. Results EGFR, IL6, TNF, and INS were found as the primary targets. The molecular docking analysis revealed the rutin interaction with the core targets. The in vitro results confirmed that rutin inhibited the growth of the MDA-MB-231 cell line. Rutin also induced cell death and decreased the expressions of IL6, TNF, INS, and EGFR. Conclusion Rutin’s multi-target effects and molecular mechanism for treating TNBC were confirmed through preliminary results. The results provide a theoretical base for rutin’s possible function in breast cancer treatment.

Background and aim Liver cancer is a prevalent and life-threatening condition, particularly among elderly individuals. The association between diabetes, a chronic metabolic disorder, and the onset and advancement of liver cancer has been widely acknowledged. However, the effect of diabetes on the survival of older patients with liver cancer has been a topic of debate. In light of this, we undertook a retrospective study to assess the impact of diabetes on the overall survival (OS) of elderly individuals diagnosed with liver cancer. Methods In this retrospective analysis, we examined clinical data from liver cancer patients aged 80 years or older who underwent diagnosis and treatment at a solitary medical center from January 2010 to December 2019. Comprehensive records encompassing baseline information, treatment protocols, diabetes history, and mortality during follow-up were meticulously documented. Employing the Kaplan–Meier method and the Cox proportional hazards model, we sought to assess the influence of diabetes on both the OS and recurrence-free survival (RFS) in elderly individuals diagnosed with liver cancer. Results This study comprised 244 elderly liver cancer patients, with 68 individuals reporting a history of diabetes. In the unadjusted Kaplan–Meier survival analysis, the diabetes group exhibited a lower OS compared to the non-diabetes group. Utilizing a multivariate Cox proportional hazards model, diabetes emerged as a prognostic factor influencing OS (hazard ratio, HR = 1.782 [1.163–2.743], P = 0.043). Regarding RFS, unadjusted Kaplan–Meier analysis revealed a diminished RFS in the diabetes group compared to the non-diabetes group. In the multivariate Cox proportional hazards model, diabetes remained a significant prognostic factor impacting RFS (HR = 1.742 [1.083–1.546], P = 0.041). Conclusion Our study indicates a significant impact of diabetes on both OS and RFS among elderly liver cancer patients. These insights may contribute to more precise guidance and recommendations for the treatment of this specific demographic, offering valuable information for healthcare practitioners working with elderly individuals diagnosed with liver cancer.

Gestational diabetes mellitus (GDM), defined as glucose intolerance occurring or first detected during pregnancy, affects approximately 8% of pregnancies worldwide. The dysfunction of trophoblasts in pregnancies complicated by GDM is associated with changes in trophoblast cell functions, resulting in compromised proliferation and regulation of the cell cycle. Cyclin B1 (CCNB1), a pivotal controller of the start of mitosis, is crucial in these mechanisms. Nevertheless, the precise function of CCNB1 in trophoblast dysfunction related to GDM has not been extensively investigated. The aim of this study was to investigate CCNB1’s role in high glucose (HG)-triggered trophoblast. Herein, we revealed that in HG-stimulated HTR8/SVneo cells, CCNB1 is highly expressed. Knockdown of CCNB1 significantly promotes the growth of HG-stimulated HTR8/SVneo cells and suppresses inflammation ( p < 0.05). Additionally, reducing CCNB1 expression significantly improves glucose uptake and inhibits the Wnt/β-catenin pathway in HG-stimulated HTR8/SVneo cells ( p < 0.05). In conclusion, our study demonstrated that the deletion of CCNB1 can alleviate trophoblast dysfunction induced by HG in GDM through the Wnt/β-catenin pathway. This suggests that CCNB1 may be a potential target for managing GDM. Although our results underscore the potential therapeutic benefits of reducing CCNB1 in mitigating trophoblast dysfunction, it is important to note that the study is limited by its reliance on a single cell line and the absence of in vivo validation. Graphical abstract

Background Severe adverse drug reactions (sADRs) are becoming increasingly common nowadays. The incidence of sADRs is approaching 6.7%, and the incidence of fatal adverse reactions is 0.32% in hospitalized patients. Of these, 48.5% are, at least potentially, preventable. Aims This study’s objective was to determine factors associated with the occurrence and preventability of sADRs occurring at the tertiary level. Methods A case-control retrospective-prospective clinical observational study design was used for the study. The research cohort included patients hospitalized at the University Clinical Center (UCC) in Kragujevac, Serbia, from January 1, 2019 to January 1, 2024. The research comprised 147 individuals who were admitted to the UCC in Kragujevac. There were 49 patients with sADRs and 98 controls. Results Significant factors associated with sADRs in our study were a total number of consultations (ORadjusted = 5.60), Charlson comorbidity index (ORadjusted = 0.30), C-reactive protein (ORadjusted = 1.07), prescribed antihistamines (ORadjusted = 14.37), and antihypertensives (ORadjusted = 0.15). Conclusion We have identified the factors that are associated with sADRs should be kept in mind while working with patients at the tertiary level. Early detection of those factors may help with early notification of sADRs and their prevention.

Chromoblastomycosis (CBM) is a chronic neglected fungal disease that causes serious damage to the physical and mental health of patients. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has garnered significant attention in the recent era for the treatment of CBM and has exhibited promising effects in several clinical case reports. We established a mice footpad infection model with Fonsecaea monophora and analyzed the impact of PDT treatment on the immune response of macrophages using single-cell sequencing. The results showed that infection of the mouse footpad skin with F. monophora results in an increase in inflammatory cells, primarily mononuclear-macrophages, with the activation of complement and enhancement of cell chemotaxis, leading to upregulation of anti-infection-related pathways. After ALA-PDT treatment, the number of inflammatory cells decreased, while macrophages upregulated the expression of antigen-recognition-related genes, enhancing phagocytosis and autophagy-related biological functions.

Introduction Qualitative and quantitative testing of ethanol in post-mortem samples is an important analytical procedure that provides accurate, precise, and reliable results. Given the complexity of the issue, obtaining a realistic picture of lifelong alcoholemia requires supporting blood ethanol findings with analyses of alternative samples, primarily vitreous humor (VH). Objective The objective of this study was to develop and validate a headspace gas chromatography with flame ionization detection (HS/GC-FID) method for determining ethanol concentration in VH. Materials and methods Conditions for the HS/GC-FID method were established and the method was validated according to the guidelines of the European Medicines Agency. Validation parameters such as precision, accuracy, specificity, sensitivity, and linearity over a wide concentration range were evaluated through statistical analysis. Results The method demonstrated precision, accuracy, specificity, and sensitivity. Additionally, it proved to be linear across a wide concentration range and relatively fast, making it suitable for rapid and routine determination of ethanol concentration in VH, particularly for forensic applications. Conclusion Results from validation and application of the method to VH samples indicate that ethanol concentration in VH can be reliably determined using the presented HS/GC-FID method, making it a valuable tool in forensic investigations.

Purpose This study aims to investigate the role and mechanism of p -hydroxyl cinnamaldehyde (CMSP) in triggering ferroptosis of small cell lung cancer (SCLC) cells. Methods The impact of CMSP on ferroptosis in H1688 and SW1271 cells was assessed through cell experiments and biological information analysis. Moreover, the expression of heme oxygenase 1 (HMOX1) in SCLC tissue was examined. Results Following CMSP treatment, a concentration-dependent increase in cell death was observed, and differentially expressed genes were found to be associated with ferroptosis. CMSP notably facilitated ferroptosis events, such as elevated levels of reactive oxygen species (ROS), Fe 2+ , malondialdehyde (MDA), transferrin receptor 1 (TFR1), divalent metal transporter 1 (DMT1), and decreased levels of glutathione (GSH), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). Furthermore, CMSP promoted mitochondrial dysfunction, manifested as reduced mitochondrial volume, increased membrane density, elevated mitochondrial ROS, and decreased mitochondrial membrane potential. Consistently, the mitochondrial-targeted antioxidant Mito-TEMPO reversed CMSP-induced ferroptosis. Expression of the HMOX1 gene was markedly increased under CMSP treatment, while lower expression was observed in cancer tissue compared to adjacent tissue. Conclusion CMSP triggers mitochondrial dysfunction via HMOX1 activation, leading to ferroptosis in SCLC cells, underscoring its potential as a therapeutic agent for SCLC.

Objective This study investigated the clinical significance of plasma sB7-H3 and YKL-40 levels in children with refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods A total of 182 RMPP patients (103 general Mycoplasma pneumoniae patients and 79 RMPP patients) were included. sB7-H3, YKL-40, and other inflammatory factors were measured. Independent factors associated with the early diagnosis of RMPP were determined. The value of each independent risk factor in predicting RMPP was evaluated. Results The RMPP group reported significantly longer hospital stays and total fever durations. Levels of C-reactive protein, D-dimer, IL-13, IL-6/-10, sB7-H3, and YKL-40 were higher in the RMPP group. sB7-H3 was positively correlated with IL-13, IL-6, and IL-4, whereas YKL-40 was positively correlated with all of the above indicators (IL-5 was also included). sB7-H3 and YKL-40 were independent risk factors for RMPP. The critical values for sB7-H3 and YKL-40 were 3.525 and 313.3 ng/mL, respectively. sB7-H3 and YKL-40 had areas under the curve of 0.734 and 0.859, respectively. YKL-40 had high sensitivity and specificity of 88.61 and 87.38%, respectively. Both indicators had predictive value, YKL-40 had the highest predictive ability for RMPP. Conclusion Detection of sB7-H3 and YKL-40 levels in the plasma may be useful in diagnosing RMPP early in the disease process.

Background Anti-angiogenesis or inhibition of blood vessel formation is the best way to prevent the growth and metastasis of tumors. Natural sources like plants are currently being explored for its antiangiogenic activity as they are factories of various phytochemicals. The goal of the current study is to investigate the antiangiogenic potential of Elaeagnus umbellata ( E. umbellata ) by using chorioallantoic membrane (CAM) assay and molecular docking. Methods Based on our previous research, the antiangiogenic activity was carried out using active fractions including crude methanol (Eu-Met), ethyl acetate (Eu-EtAc), and chloroform (Eu-Chf) extracts using CAM assay. Furthermore, to understand the binding mechanism of identified compounds, molecular docking was performed against vascular endothelial growth factor receptor 2 (VEGFR-2) using AutoDock vina as docking software. VEGFR-2 is overexpressed in pathological angiogenesis. Results In CAM assay, Eu-Met, Eu-EtAc, and Eu-Chf extracts showed antiangiogenic activities but notable antiangiogenic activities were exhibited by Eu-Chf with IC 50 value of 65.02 μg/mL. In molecular docking, five compounds, catechin, catechin hydrate, morin, quercetin, and rutin, reported in the extract and active fractions (Eu-Met, Eu-EtAc, and Eu-Chf) of E. umbellata showed strong interactions with VEGFR-2 with binding affinities of −9.4, −9.3, −9.9, −10.2, and −9.4 kcal/mol. Conclusion Based on our results, we can claim that E. umbellata possess antiangiogenic activity which needs to be explored further.

Background Radical gastrectomy is generally prefered for gastric cancer but has postoperative complications. The objectives of the study are to evaluate the effectiveness of three different models of preoperative counseling and postoperative follow-up care in patients who underwent radical gastrectomy for gastric cancer. Methods In retrospective medical record analyses, patients received nurse-led preoperative counseling and postoperative follow-up care (NC cohort, n = 105) or surgeon-led preoperative counseling and surgeon-led follow-up (SC cohort, n = 140), or did not receive counseling and aftercare (RC cohort, n = 160). Results Patients had a postoperative intensive care unit (PICU) stay of 24 (26–22) h/patient and postoperative pain of 6 (6–5)/ patient. The frequencies of nausea, vomiting, medical intensive care unit admission(s), dizziness, length of PICU stay, and intensity of postoperative pain were lower among patients in the NC cohort, followed by those in the SC and RC cohorts. A higher number of patients in the RC cohort died when compared to the NC (25 [16%) vs 2 [2%], p = 0.0458) and the SC (25 [16%] vs 11 [8%], p = 0.0001) cohorts in follow-up. Conclusion Patients who undergo radical gastrectomy for gastric cancer require healthcare professional-led preoperative counseling and postoperative aftercare. Nurse-led preoperative counseling and postoperative aftercare, could improve outcome measures in patients who underwent radical gastrectomy for gastric cancer. Graphical abstract

Background Early-stage breast cancer requires effective surgical interventions. This meta-analysis compares the therapeutic efficacy of endoscopic minimally invasive surgery (EMIS) with traditional surgery, such as modified radical mastectomy. Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Patient, Intervention, Comparison, Outcome model, we systematically searched PubMed, Embase, Web of Science, and the Cochrane Library until July 19, 2023. We included comparative trials, focusing on randomized controlled trials, retrospective, and prospective studies. Metrics analyzed included operative time, blood loss, postoperative drainage volume, and lymph node harvest using Stata version 17. Results Out of 943 studies, six met the inclusion criteria. Endoscopic surgery had a longer operative time (weighted mean difference [WMD] = 1.03, P < 0.01) but significantly less blood loss (WMD = −1.48, P < 0.01). No significant differences were noted in drainage volume and lymph node harvest. Conclusions EMIS reduces intraoperative blood loss but requires more time than traditional surgeries. Both methods show comparable outcomes in postoperative drainage and lymph node harvest, supporting their efficacy in treating early-stage breast cancer.

Background Macrophage accumulation found in biopsy specimens of patients with dilated cardiomyopathy (DCM) has been thought to reflect chronic myocarditis. However, it is unsettled whether they are responsible for the active or persistent phase of the disease. Objective The aim of this study was to count the number of macrophages in relation to plasma concentrations of cardiac troponin T (cTnT). Methods We studied the biopsies of 181 patients with DCM by immunohistochemistry using anti-CD68(+) antibodies. The total number of CD68(+) and the number of CD68(+) cells attached to injured cardiomyocytes were counted and presented as the number of cells/mm 2 . Results Two expression patterns of CD68(+) macrophages were observed: those localized freely in the interstitial space only, and the cells attached to injured cardiomyocytes. As regards macrophages adhered to injured cardiomyocytes, 72 out of 181 (39.8%) patients presented these cells in the biopsy sections. Both the total number of CD68(+) macrophages and the number of CD68(+) cells directly adhered correlated negatively with cTnT in the serum of DCM patients (Spearman’s rho, r = −0.45, P < 0.001 and r = −0.31, P = 0.009, respectively). Conclusion Macrophages attached to injured cardiomyocytes may reflect chronic (ongoing) inflammation in the myocardium.

Background & aims There was considerable debate regarding the effect of statins administration on the outcome of septic patients. This retrospective study aimed to assess the association between statins administration and mortality in sepsis patients and investigate whether this association differed according to the types of statins. Methods We performed a retrospective study based on the electronic ICU Collaborative Research Database, Medical Information Mart for Intensive Care Database, and the Amsterdam University Medical Centers Database. The participants with sepsis were divided as two groups, statins group and non-statins group. The primary endpoint was the all-cause mortality. We utilized logistic regression, propensity score matching (PSM), and sub-analysis to assess the association between statins administration and outcome in patients with sepsis. Results A total of 19,327 sepsis patients were enrolled. Among these, 3,721 patients were prescribed statins. Pooled analyses of three databases showed that statin users had a decreased risk of mortality in sepsis as compared with nonusers (OR 0.73, 95% CI 0.66–0.80, P < 0.001). Sub-analysis of statin showed that atorvastatin had the most distinct effectiveness in decreasing mortality (OR 0.67, 95% CI 0.59–0.76, P = 0.035), whereas pravastatin, simvastatin, and rosuvastatin were not. PSM analysis confirmed these findings for statins (OR 0.75, 95% CI 0.67–0.84, P < 0.001) and atorvastatin (OR 0.70, 95% CI 0.59–0.82, P < 0.001). Conclusions The use of statins could decrease the risk of mortality in patients with sepsis during the hospital period. Among different types of statins, atorvastatin showed the most significant trend to reduce the risk of mortality in patients with sepsis.

Background It is unclear how the estimated glucose disposal rate (eGDR) index relates to osteoarthritis (OA). The goal of this research is to explore the possible link between the eGDR index and the likelihood of OA development. Methods The study encompassed 9,051 individuals from the National Health and Nutrition Examination Survey (2011–2018). Participants were divided into quartiles according to their eGDR, calculated with the equation: eGDR (mg/kg/min) = 21.158 − (0.09 × waist circumference) − (3.407 × hypertension) − (0.551 × glycosylated hemoglobin). We assessed the independent correlation between the eGDR metric and the incidence of OA through weighted multivariate regression, stratified analysis, and threshold effect evaluation. Results The study encompassed 9,051 participants, who had an average eGDR of 7.09. Participants with OA had lower eGDR levels compared to those without OA (6.27 ± 0.09 vs 7.31 ± 0.06, P < 0.001). The odds ratios (ORs) for OA associated with the eGDR index in the logistic regression models were 0.87 (95% confidence interval [CI]: 0.84, 0.89) in the unadjusted model I and 0.87 (95% CI: 0.84, 0.91) in model II (adjusted for all covariates). Higher eGDR index was associated with a reduced risk of OA when compared to the lowest quartile (Q1). A restricted cubic spline analysis indicated a linear negative relationship between eGDR and OA risk. Conclusion An increased eGDR index is inversely related to the risk of OA. The eGDR may serve as a valuable biomarker for the detection of OA and offers a new perspective for the assessment and management of the condition.

Background The highly infectious coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, the seventh coronavirus. It is the longest pandemic in recorded history worldwide. Many countries are still reporting COVID-19 cases even in the fifth year of its emergence. Objective The performance of various machine learning (ML) and deep learning (DL) models was studied for image-based classification of the lungs infected with COVID-19, pneumonia (viral and bacterial), and normal cases from the chest X-rays (CXRs). Methods The K -nearest neighbour and logistics regression as the two ML models, and Visual Geometry Group-19, Vision transformer, and ConvMixer as the three DL models were included in the investigation to compare the brevity of the detection and classification of the cases. Results Among the investigated models, ConvMixer returned the best result in terms of accuracy, recall, precision, F 1-score and area under the curve for both binary as well as multiclass classification. The pre-trained ConvMixer model outperformed the other four models in classifying. As per the performance observations, there was 97.1% accuracy for normal and COVID-19 + pneumonia-infected lungs, 98% accuracy for normal and COVID-19 infected lungs, 82% accuracy for normal + bacterial + viral infected lungs, and 98% accuracy for normal + pneumonia infected lungs. The DL models performed better than the ML models for binary and multiclass classification. The performance of these studied models was tried on other CXR image databases. Conclusion The suggested network effectively detected COVID-19 and different types of pneumonia by using CXR imagery. This could help medical sciences for timely and accurate diagnoses of the cases through bioimaging technology and the use of high-end bioinformatics tools.

Background The specific role of lysophosphatidic acid 2 (LPA 2 ) in deep vein thrombosis (DVT) remains unclear. Methods An inferior vena cava annulus retraction model of DVT was established in wild-type (WT) and global LPA 2 knockout ( Lpar2 −/− ) mice. We examined the incidence of DVT, wet weight of thrombus, length of thrombus, assessed endothelial permeability through Evans blue dye assay in vivo, cell viability, and endothelial cell (EC) permeability of mouse inferior vena cava ECs in vitro. Proteomics, histopathology, immunohistochemistry, and western blotting were employed to investigate the role of LPA 2 in DVT. Results Lpar2 deficiency increased vascular endothelial permeability and promoted the progression of DVT. Histological examination revealed aggravated inflammation in the thrombus of Lpar2 −/− DVT mice. In vitro , Lpar2 −/− resulted in increased permeability of ECs. Proteomic results indicated that DVT after Lpar2 −/− may be related to tight junction (TJ) protein. LPA 2 agonist, 2-[4-(1,3-dioxo-1 H ,3 H -benzoisoquinolin-2-yl)butylsulfamoyl] benzoic acid, significantly reduced vascular endothelial permeability as well as increased expression of the vascular endothelial TJ protein zonula occludens-1. Conclusion These data provide a novel mechanism of endothelial barrier protection of LPA 2 in DVT.

Background Mitochondria play a central, multifunctional role in cancer progression. However, the mechanism of mitochondrial genes in epithelial ovarian cancer (EOC) remains unclear. This study aimed to screen candidate mitochondrial genes in EOC and then to investigate their biological functions and potential mechanisms. Methods We downloaded Gene Expression Omnibus RNA-seq profiles and identified mitochondrial differentially expressed genes in EOC by bioinformatics analysis. Transcription factor A, mitochondrial (TFAM) expression in EOC tissues was determined by immunohistochemistry. In vitro assays were applied to clarify TFAM function in EOC. Results The bioinformatics analysis results showed that the mitochondrial genes TFAM , HSPE1 , and CYC1 were significantly upregulated ( P < 0.05) in EOC, and their upregulation was associated with a poor prognosis. TFAM was highly expressed in EOC tissues and significantly associated with clinical stage ( P = 0.004), lymph node metastasis ( P = 0.043), and overall survival ( P < 0.05). Silencing TFAM in EOC cells significantly inhibited cell proliferation and migration and induced cell apoptosis ( P < 0.05). Conclusion TFAM promotes EOC cell secretion of VEGF-A, VEGF-C, VEGF-D, lymphangiogenesis, and EOC lymph node metastasis. Our results may provide new insights into the biological functions and potential mechanisms of TFAM in EOC, which might provide new targets for EOC diagnosis and treatment.

Background and objective Early nutritional support holds paramount importance for postoperative gastric cancer (GC) patients. Peptidase M20 domain containing 1 (PM20D1) is a secretory enzyme associated with glucose and lipid metabolism. However, there is a dearth of clinical studies delving into the connection between PM20D1, lipid metabolism, and inflammatory factors in GC patients who have received enteral nutrition (EN). This research aimed to investigate the serum levels of PM20D1 in GC patients following early EN and their potential associations with lipid metabolism, nutritional markers, and inflammatory factors. Methods This prospective observational study enrolled 180 GC patients between May 2020 and July 2022. On the first postoperative day, all patients received EN support, which was maintained for a duration of 5 days. Serum levels of PM20D1, interleukin (IL)-6, IL-1β, and C-reactive protein were measured on the sixth day after surgery using an enzyme-linked immunosorbent assay. Data on demographics, clinical statistics, lipid metabolism, nutritional parameters, and the prognostic nutritional index (PNI) were collected. Patients were followed up for 12 months, and both overall survival and disease-free survival were recorded. Results In the low PNI group, the serum levels of PM20D1, albumin (ALB), and blood lymphocytes (BL) showed significant reductions. Pearson analysis revealed a negative correlation between PM20D1 and IL-6 levels, whereas a positive correlation emerged between PM20D1 and ALB and BL levels. Furthermore, PM20D1 demonstrated potential as a biomarker for diagnosing poor nutritional status (PNI < 43) in GC patients and was a risk factor for poor nutritional status in GC patients. Conclusion Serum PM20D1 remarkably declined in GC patients after early EN and was associated with poor nutritional status.

Purpose Emergence agitation (EA) after (adeno)tonsillectomy (AT) surgery impairs recovery in children. Adequate analgesia plays a crucial role in reducing EA incidence. This study investigated whether hydromorphone infusion (30 μg/kg) during anesthesia induction could reduce EA following AT surgery for obstructive sleep apnea in children. Patients and methods A total of 186 ASA I–III children aged 3–7 years undergoing AT surgery were enrolled in a blinded randomized trial comparing hydromorphone (30 μg/kg) to fentanyl (4 μg/kg). The primary outcome was EA incidence within 30 min post-extubation. Secondary outcomes included pediatric anesthesia emergence delirium (PAED), face, legs, activity, crying, consolability (FLACC), Ramsay sedation scores, extubation time, rescue analgesia incidence, and adverse events. Results The incidence of EA was significantly lower in the hydromorphone group [48.4% (45/93) vs 64.5% (60/93); absolute difference: 16.1%; 95% CI: 18.9–29.5%; P = 0.027]. Hydromorphone improved PAED, FLACC, and Ramsay scores and reduced moderate-to-severe pain and rescue analgesia. No postoperative complications occurred in either group. Conclusion Hydromorphone at 30 μg/kg effectively reduces the incidence of EA within 30 min post-extubation in children after AT surgery compared to fentanyl. It shows superior analgesia and has a low incidence of adverse effects.

Aim The aim of this study is to determine the effect of vitamin D replacement therapy on sleep habits in restless legs syndrome (RLS) patients with vitamin D deficiency. Methods The study was conducted between September 1, 2018, and September 1, 2019, at the Pediatrics outpatient clinic of Bezmialem Vakif University. 46 cases with RLS and 43 healthy controls between these dates were included in the study. The Children’s Sleep Habits Questionnare was filled out retrospectively by parents. Results While vitamin D supplementation was given to 20 children with RLS who were found to have vitamin D deficiency, the 26 patients without vitamin D deficiency did not receive supplementation. There was no significant difference between the treatment groups in terms of gender, age, and pre-treatment sleep habits. Compared to the pre-treatment period, post-treatment bedtime resistance, sleep onset delay, sleep anxiety, parasomnias, daytime sleepiness, and CSHQ total score were significantly improved in RLS cases with vitamin D deficiency. There were no significant differences in RLS patients without vitamin D supplementation. Other comparisons also showed no difference between groups. Conclusion There was no difference between the sleep habits of RLS cases with and without vitamin D deficiency. Sleep habits improved positively after vitamin D supplementation in patients with vitamin D deficiency compared to the pre-treatment period. There was no difference in the sleeping habits of RLS patients without vitamin D deficiency during the same period. Vitamin D supplementation can improve sleep habits in patients with RLS.

Background Oxaliplatin (OXA) is among the most common chemotherapy drugs and is the base component of the FOLFOX regimen (OXA + leucovorin + 5-fluorouracil) and CapeOX regimen (OXA + capecitabine). Resistance to and failure of these two OXA-based regimens often results in poor outcomes in patients with colorectal cancer (CRC). Nitrendipine (NTD) is a first-line antihypertensive drug commonly used in hypertension and coronary heart disease with confirmed low toxicity and side effects. However, the potential benefits of NTD for CRC progression and therapy remain unclear. Methods Cell counting kit-8 (CCK-8) detection, colony formation assay, wound-healing assay, Transwell assay, SynergyFinder webtool, and subcutaneous tumor models were used to assess the effect of NTD with OXA on CRC inhibition in vitro and in vivo . Bioinformatics tools including Human Protein Atlas (HPA), quantitative real-time polymerase chain reaction, western blotting analyses, lentivirus transfection, and rescue experiment were used to investigate the mechanism(s) of the related action. Results Utilizing murine and human CRC cell lines, the in vitro and in vivo experiment demonstrated that NTD inhibited cell proliferation, migration, and invasion, and the synergy scores calculated by SynergyFinder indicated that NTD exhibited synergistic activity with the chemotherapeutic drug OXA. The CCK-8 detection, animal model, and rescue experiment results demonstrated that NTD suppressed CRC progression and potentiated OXA therapeutic effect by downregulating calcium voltage-gated channel subunit alpha1 D (CACNA1D). Conclusions This study presents novel data on first-line antihypertensive NTD, exerting inhibitory effects on cell proliferation and migration in CRC and revealing synergistic activity with OXA by downregulating CACNA1D. NTD may be a candidate as a promising chemosensitizer as an OXA new combination to improve the efficacy and safety of CRC therapy.

Background: Health literacy (HL) and irrational beliefs about happiness significantly influence adults’ health-related quality of life (HRQoL). The purpose of this study was to examine whether irrational happiness mediates the relationship between HL and HRQoL among adults. Methods: A total of 686 adults (468 women and 218 men; mean age = 22.30  ±  6.83 years) completed self-report questionnaires, including the Health Literacy Scale-Short Form, the EUROHIS-QOL 8, and the Irrational Happiness Beliefs Scale. Data were analyzed using structural equation modeling and bootstrapping methods. Results: HL had both direct ( β = 0.260, p < 0.01) and indirect effects on HRQoL. HL directly predicted irrational happiness ( β = –0.369, p < 0.01), which in turn directly predicted HRQoL ( β = –0.318, p < 0.01). Specifically, irrational happiness significantly mediated the relationship between HL and HRQoL (bootstrap coefficient = 0.117, 95% CI = 0.071–0.175). Conclusion: These findings suggest that interventions aiming to enhance adults’ HRQoL should consider not only improving HL but also addressing irrational beliefs about happiness.

Background Osteoporosis (OP) is a systemic bone disorder marked by reduced bone mass and disrupted microstructure, leading to higher fracture risk. Epidemiological data from China show a 20.7% prevalence in women and 14.4% in men over 50, underscoring a pressing health issue given the aging population. More drugs to inhibit OP progression should be explored, and their biological mechanisms confirmed in preclinical studies. Methods In this study, we utilized Lycium barbarum polysaccharide (LBP), an extract from the traditional Chinese medicine Goji Berry. LBP, known for its range of pharmacological activities, was assessed for its potential therapeutic effects on OP. We specifically investigated its influence on the proliferation, apoptosis, migration, and functional differentiation of osteoblasts and osteoclasts. Results LBP significantly promotes osteoblast proliferation, migration, and osteogenic differentiation. Conversely, it inhibits the intrinsic apoptotic response in osteoblasts. For osteoclasts, LBP suppressed their proliferation, migration, and osteoclastic differentiation while enhancing their natural apoptosis. These results were confirmed by classical protein pathway detection experiments. Conclusion LBP showcases potential therapeutic properties against OP, particularly in modulating osteoblast/osteoclast activities. While its exact mechanisms through vital signaling pathways remain to be fully elucidated, LBP’s prominent effects suggest that it is a promising agent for OP intervention, warranting further in-depth studies.

Background and purpose Gastric cancer is a kind of malignant tumor with high incidence and high mortality, which has strong tumor heterogeneity. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on gastric cancer cells. However, its chemical and pharmacological profiles remain to be elucidated. In the current study, we aimed to reveal the mechanism of PT in treating gastric cancer cells through metabolomic analysis and network pharmacology. Methods Metabolomic analysis of two strains of gastric cancer cells treated with the Pinellia ternata extract (PTE) was used to identify differential metabolites, and the metabolic pathways were enriched by MetaboAnalyst. Then, network pharmacology was applied to dig out the potential targets against gastric cancer cells induced by PTE. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape. Results The PTE was confirmed to significantly inhibit cell proliferation, migration, and invasion of HGC-27 and BGC-823 cells. The results of cellular metabolomics showed that 61 metabolites were differently expressed in gastric cancer cells of the experimental and control groups. Through pathway enrichment analysis, 16 metabolites were found to be involved in the glycerophospholipid metabolism, purine metabolism, sphingolipid metabolism, and tryptophan metabolism. Combined with network pharmacology, seven bioactive compounds were found in PT, and the networks of bioactive compound–target gene–metabolic enzyme–metabolite interactions were constructed. Conclusions In conclusion, this study revealed the complicated mechanisms of PT against gastric cancer. Our work provides a novel paradigm to identify the potential mechanisms of pharmacological effects derived from a natural compound.

Background Non-alcoholic fatty liver disease (NAFLD) is a globally widespread disease. Recent investigations have highlighted a close association between immunity and NAFLD, but the causality between them has not been thoroughly examined. Methods A total of 731 immunological traits and NAFLD cohorts were derived from genome-wide association study summary data, and single nucleotide polymorphisms significantly associated with immune traits were identified as instrumental variables. Moreover, 731 phenotypes include absolute cell counts, median fluorescence intensity (MFI), morphological parameters, and relative cell counts. The bidirectional two-sample Mendelian randomization (MR) was performed primarily using the inverse-variance weighted methods, and sensitivity analysis was carried out simultaneously. Results Four immunophenotypes were identified to exert a protective effect against NAFLD, including HLA-DR + CD4 + %lymphocytes, SSC-A on CD4 + , CD24 MFI on IgD − CD38 − , and CD8 MFI on CD28 − CD8 br . Seven immunophenotypes were identified to be hazardous, including CD28 + CD45RA + CD8 dim %CD8 dim , CD127 MFI on CD28 + DN (CD4 − CD8 − ), CD20 MFI on IgD + CD38 br , CD20 MFI on transitional, IgD MFI on transitional, CD3 MFI on central memory CD8 br , and CD45 MFI on CD33 br HLA-DR + CD14 − . However, reverse MR showed NAFLD had no causal effect on immunophenotypes. Conclusion The study demonstrated a potential causal link between several immunophenotypes and NAFLD, which contributes to advancing research and treatment of NAFLD based on immune-mediated mechanisms.

Objective To summarize the clinical characteristics, diagnosis, and treatment experience of human immunodeficiency virus (HIV) infection combined with acute leukemia. Methods Ten patients with HIV infection (eight males, two females; mean age of 40 years) were diagnosed with acute leukemia. Clinical features, diagnosis, treatment, and outcomes of these patients were retrospectively analyzed. Results Among these ten patients, eight acute myeloid leukemia cases and two acute lymphoblastic leukemia cases were L3; three cases of M3 were positive for the promyelocytic leukemia and Vitamin A acid receptor alpha (PML/RARA) fusion genes, and four cases presented multiple chromosomal structural and numerical abnormalities. CD4+ T cell counts of the ten patients ranged from 84 to 389 cells/μL with a mean of 253.5 cells/μL. Among six patients who received chemotherapy, three cases were alive, two died of sepsis secondary to myelosuppression after chemotherapy, and one was lost to follow-up. Among four patients who did not receive chemotherapy, three died, one had M3 treatment and died with cerebral hemorrhage, and one was lost to follow-up. The maximum survival time was 74 months. Conclusion HIV combined with acute leukemia has a complex presentation and rapid progression, early diagnosis and timely initiation of standard chemotherapy along with active antiviral therapy can improve patient’s survival.

Purpose The aim of this research study is to assess the ability of quercetin to protect the heart from the negative consequences of tacrolimus-induced cardiotoxicity. Methods A total of 30 rats were divided into 5 groups. Tacrolimus was used to induce cardiotoxicity, whereas quercetin was employed as a protective agent. Results Tacrolimus administration significantly raised the levels of serum cardiac biomarkers (Lactate dehydrogenase, creatine kinase-myocardial band, and troponin-I) as well as inflammatory biomarkers (tumor necrosis alpha and interleukin 6). The administration of quercetin reduced raised levels of cardiac and inflammatory biomarkers significantly. In addition, treatment with tacrolimus resulted in higher malondialdehyde (MDA) (lipid peroxidation marker) levels and falling in the levels of reduced glutathione (GSH) as well as antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT). Quercetin treatment significantly reduced MDA levels and increased GSH and antioxidant enzyme (SOD, GR, and CAT) levels. Moreover, the tacrolimus-administered group exhibited histological changes in cardiac tissue cited as vacuole formation, large and uncondensed nucleus, and cardiomyocyte hypertrophy. The quercetin treatment reduced the inflammatory cell infiltration in cardiac tissue and thus reduced vacuole formation and hypertrophy. Conclusions The outcome showed quercetin’s cardioprotective potential against tacrolimus-administered cardiotoxicity. Consequently, it is concluded that quercetin may be used as add-on therapy with tacrolimus to reduce cardiac adverse effects. Graphical abstract

Objective The purpose of this article was to unravel the clinical efficacy of probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema in the treatment of mild-to-moderate ulcerative colitis (UC). Methods Eighty-six mild-to-moderate UC patients were selected as study subjects and randomized into the control group (treated with mesalazine enteric-coated tablets [Salofalk]) and the observation group (treated with mesalazine enteric-coated tablets, Bifidobacterium Tetravaccine Tablets, and Yiyi Baitouweng Decoction retention enema). The clinical efficacy, colonoscopy score, serum levels of inflammatory factors, and the incidence of adverse reactions were compared. Results The clinical efficacy of patients in the observation group was better in contrast to the control group. After 8 weeks of treatment, the colonoscopy score, and levels of TNF-α, IFN-γ, CRP, and ESR were lower, while IL-10 levels were higher in patients of both groups than those before treatment; lower colonoscopy score and levels of TNF-α, IFN-γ, CRP, and ESR and higher IL-10 levels were observed in the observation group versus the control group. Conclusion Probiotics combined with mesalazine and Yiyi Baitouweng Decoction retention enema have remarkable clinical effects in treating mild-to-moderate UC. Graphical abstract

Introduction Assess the feasibility of utilizing the ratio of blood inflammation to coagulation markers as a potential periprosthetic joint infection (PJI) diagnostic tool. Materials and methods A retrospective analysis was conducted, involving 133 PJI and 93 aseptic loosening patients. Levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count, mean platelet volume, fibrinogen, D-dimer, and ratios of CRP to fibrinogen, ESR to fibrinogen, platelet count and mean platelet volume ratio (PC/MPV), and D-dimer were compared. Receiver operating characteristic curves and Youden’s index were employed to assess the diagnostic efficacy of these biomarkers. Results PJI patients had significantly higher levels of CRP, ESR, PC/MPV ratio, fibrinogen, D-dimer, CRP/(PC/MPV) ratio (CPR), CRP/D-dimer, CRP/fibrinogen (CFR), ESR/(PC/MPV) ratio, ESR/D-dimer, and ESR/fibrinogen. Area under the curve (AUC) values for fibrinogen, CRP, and ESR in diagnosing PJI were comparable. AUC values for CPR and CFR were akin to those of ESR. AUC values for combined CRP and CPR, combined CRP and fibrinogen, combined CRP and CFR, and combined ESR and fibrinogen in diagnosing PJI were akin to that of combined CRP and ESR. Conclusions Fibrinogen, CPR, CFR, combined CRP and CPR, combined CRP and fibrinogen, combined CRP and CFR, and combined ESR and fibrinogen could be considered as new adjunct markers for diagnosing PJI.

Background Males have a three times higher risk of a diagnosis of bladder cancer (Bca) than females. Sex hormone-binding globulin (SHBG) may be associated with Bca risk. However, the sex-specific role of SHBG in Bca remains unclear. In this study, we aimed to determine the role of SHBG in Bca. Methods A sex-specific univariable Mendelian randomization (MR) analysis involving 369,426 men and 395,375 women was conducted to assess the causal relationship between SHBG and testosterone and Bca risk. Sensitivity analyses and multivariable MR were conducted to confirm the robustness of our results. Linkage disequilibrium score regression assessed the genetic correlation between these diseases influenced by heredity. Results Univariable MR results showed that one-SD elevated SHBG was related to a low risk of Bca in males (OR: 0.60, 95% CI: 0.39–0.93; p = 0.022) but had no benefit in females. Genetically predicted BT was positively associated with Bca risk in males (OR: 1.59; 95% CI: 1.06–2.40; p  =  0.027). In multivariable MR, higher SHBG levels were not related to male Bca risk after controlling for BT. Conclusions Our findings do not provide evidence to support a causal relationship between SHBG and Bca risk in males although an association was observed in the univariable analysis. Further research is needed to identify the underlying pathways.

Objective The aim of this study was to examine the impact of stability-focused core muscle strength training coupled with respiratory techniques on diminishing the inter-recti distance (IRD) among postpartum women. Methods A total of 106 women diagnosed with diastasis recti abdominis within 42 days following delivery were 1:1 randomly allocated into a control group ( n = 53) and an intervention group ( n = 53). Both groups underwent standard postpartum follow-up care and independently pursued self-directed rehabilitation exercises. Additionally, the intervention group commenced a 6-week program of core muscle strength stability-oriented breathing training 42 days postpartum. Measurements of IRD were taken both pre- and post-intervention. Results Prior to the intervention, no statistically significant difference in IRD was observed between the two groups ( P > 0.05). Subsequent to the intervention, notable reductions in IRD measurements were evident above, at the level of, and below the umbilicus in both groups compared to baseline measurements (intervention group: P < 0.001 at all measured points; control group: P = 0.035 above the umbilicus, P < 0.001 at the level of, and below the umbilicus). However, the intervention group exhibited a more pronounced decrease in IRD at all measured points when compared to the control group, demonstrating statistical significance with P = 0.000. Conclusion Core muscle strength stability-oriented breathing training demonstrates efficacy in reducing IRD among postpartum women.

Introduction Transsphenoidal endoscopic pituitary (TEP) tumor resection is performed through the nose via the sphenoid sinus to remove tumors from the pituitary gland. Also, enhanced recovery after surgery (ERAS) was adapted to reduce physical and physiological traumatic stress response of surgical patients. Methods A total of 174 patients who underwent TEP tumor resection in our department from August 2021 to June 2022 were randomly divided into non-ERAS group and ERAS group. The main primary observational indicator was postoperative self-care ability parameters such as early urethral catheters’ removal and postoperative food intake. Also, secondary indicators such as postoperative complications, average length of hospital stay (LOS), and total hospital cost were compared. Results The overall self-care ability of the ERAS group was higher than that of the non-ERAS group 24 h after surgery (35 points vs 20 points, p < 0.001). Also, food intake on the first day after surgery was higher than that of the non-ERAS group ( p < 0.001). Furthermore, the average LOS in the ERAS group was lower than that of the non-ERAS group (4 days vs 7 days, p < 0.01). Additionally, the average hospitalization cost in the ERAS group was lower than that of the non-ERAS group (32, 886 RMB vs 48, 125 RMB, p < 0.001). Conclusion ERAS nursing strategy promoted early recovery of self-care, shorten the average LOS, and reduce hospitalization costs without increasing the incidence of postoperative complications.

Objective This study aimed to investigate the serum levels of interleukin (IL)-17A in patients with traumatic bowel rupture and its clinical significance, particularly its correlation with inflammatory cytokines, preoperative severity, and postoperative prognosis. Methods A total of 104 patients with traumatic bowel rupture admitted to Ruian People’s Hospital between February 2021 and June 2024 were included in this prospective observational study. All patients underwent standard surgical treatment for traumatic bowel rupture at our hospital. Serum levels of IL-17A, IL-6, tumor necrosis factor-alpha, and C-reactive protein were measured at various time points using enzyme-linked immunosorbent assay. Clinical data and demographics were collected. Patients were followed up for 3 months post-discharge. Results The study found significantly higher levels of IL-17A and IL-6 in patients with an injury severity score (ISS) of ≥16 compared to those with an ISS of <16 ( p < 0.05). Serum IL-17A levels were particularly elevated in patients with poor prognosis ( p < 0.05). Of particular importance, receiver operating characteristic curve analysis demonstrated that serum IL-17A levels at 72 h post-surgery had predictive value for poor prognosis, with an area under the curve of 0.773, a cutoff value of 41.75 pg/mL, a sensitivity of 62.2%, and a specificity of 83.6%. Logistic regression analysis identified elevated IL-17 levels at 72 h post-surgery as a significant risk factor for poor prognosis (odds ratio = 1.273, 95% confidence interval: 1.115–1.453, p < 0.001). Conclusion In summary, our study highlights the significant potential of serum IL-17A as a biomarker for predicting poor prognosis in patients with traumatic bowel rupture post-surgery, suggesting its utility in clinical assessment and potential as a therapeutic target.

Background Family caregiving for dementia patients is a challenging task, with profound effects on caregivers’ physical and mental well-being. The purpose of this study was to explore the impact of Kolb’s experiential learning theory on the caregiving burden and psychological status of caregivers for dementia patients. Methods This study enrolled 110 caregivers of nursing dementia patients. These caregivers were divided into two groups: a control group ( n = 55) and an intervention group ( n = 55). The control group received routine care, while the intervention group received nursing based on Kolb’s experiential learning theory in addition to routine care. Changes in caregiving burden and psychological status were compared between the two groups before and after the intervention. Result The results showed that after the intervention, the intervention group’s caregivers had significantly lower scores on the caregiver burden inventory dimensions and total score compared to the control group ( P < 0.05). Additionally, the intervention group’s self-assessment scores on the self-rating anxiety scale and self-rating depression scale were also lower than those of the control group ( P < 0.05). Conclusion Kolb’s experiential learning theory has a positive impact on alleviating the caregiving burden and reducing anxiety and depression among family caregivers of dementia patients.

Objective This study analyzed the prognosis of patients with high-grade squamous intraepithelial lesion (HSIL) after loop electrosurgical excision procedure (LEEP) and elucidated the predictive value of neutrophil-to-lymphocyte ratio (NLR) and margin condition in relation to prognostic recurrence. Methods A total of 209 patients were included, with 46 cases in the recurrence/residual group, 156 cases in the no recurrence/residual group, and 7 cases lost to follow-up. General information, past history and comorbid underlying diseases, laboratory tests, and other relevant clinical information were compared between the two groups. The ROC curves were plotted to assess the diagnostic values of NLR, platelet-to-lymphocyte ratio (PLR), and lymphocytes. Log-rank test was conducted to plot the Kaplan Meier curves to assess the occurrence of recurrence/residual. Risk factors for the occurrence of recurrence/residual in patients during follow-up were analyzed. Results Patients with high-risk human papillomavirus (HR-HPV) infection, positive margins, and higher PLR and NLR had a higher risk of recurrence/residual at follow-up. HR-HPV infection, positive margins, and higher levels of PLR and NLR showed significant hazard ratios. High NLR, positive margins, and HR-HPV infection resulted in poor prognosis and the occurrence of recurrence or residual. Conclusion NLR levels and positive margins may be markers for predicting HSIL recurrence/residual lesions after LEEP.

Background The Commiphora gileadensis ( C. gileadensis ) is a tree belonging to the genus Commiphora. Aim of the study: This study investigates the effect of C. gileadensis on erectile dysfunction and infertility in male mice. Methods Fifty male BALB/c mice are divided into five groups: control, untreated diabetic, diabetic C. gileadensis sap-treated, methanol extract-treated, and acetone extract-treated. All groups were assessed for body weight, testicular weight, serum follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin, nitric oxide, adropin, endothelin levels, semen analysis, CD4 + , CD8 + , CD25 + , and testicular nitric oxide synthase (NOS) immunoreactivity. Outcome C. gileade nsis maintains sexual integrity and infertility in mice. Results Diabetic groups treated with C. gileadensis had significantly higher body weight than the untreated group. Furthermore, the diabetic group treated with C. gileadensis sap had significantly increased testicular weight than the untreated groups. Diabetic groups treated with C. gileadensis had significantly greater testosterone levels than the untreated groups. Additionally, these groups exhibit considerably higher nitric oxide and adropin levels than the untreated diabetic group. Endothelin levels were considerably lower in diabetic groups treated with C. gileadensis than in the untreated group. Semen analysis shows that the diabetic group treated with C. gileadensis sap had considerably more sperm count than the untreated group ( P < 0.05). CD4 + , CD8 + , CD4 + , CD25 + , and CD8 + CD25 + were reduced significantly in diabetic mice treated with C. gileadnesis . In addition, the NOS immunoreactivity is greater in diabetic C. gileadensis treated groups than in the untreated group. Clinical implications C. gileadensis induces mice erectile function and fertility. Strength and limitations The study does not use laser Doppler flowmetry for the measurement of erectile dysfunction. Conclusion C. gileadensis ameliorates infertility and erectile dysfunction in diabetic mice.

Background Epithelial–mesenchymal transition (EMT) and circulating tumor cells (CTCs) are key prognostic factors in nasopharyngeal carcinoma (NPC). However, the role of EMT status in CTCs for predicting outcomes in advanced NPC treated with radiotherapy after induction chemotherapy remains unclear. Methods A total of 143 CTC tests from 95 advanced/metastatic NPC patients were analyzed before, during, and after radiotherapy, with a 60-month follow-up. CTC count, matrix metalloproteinase 2 (MMP2)) protein expression, and EMT subtypes were examined. Results During radiotherapy, CTC counts increase but decrease afterward. Patients with higher pre-radiotherapy tumor-node-metastasis (TNM) stages have lower total and M-subtype CTC counts. Higher T and TNM stages during radiotherapy correlate with increased EMT-state CTCs, especially hybrid CTCs. EA/IgG-positive patients have a higher number of hybrid CTCs and E-type (epithelial + hybrid) CTCs, while EBV-EA-negative patients have more mesenchymal CTCs. A higher post-radiotherapy CTC count predicts relapse, and the positive rate of MMP2 expression on hybrid and epithelial CTCs is higher than that on mesenchymal CTCs. Conclusion EMT status, particularly in hybrid CTCs, is a potential prognostic marker for relapse in advanced NPC after radiotherapy.

Background Tetrahydropalmatine (THP) regulates mitochondrial function in vascular smooth muscle cells (VSMCs) to prevent or alleviate atherosclerosis (AS), with unclear specific mechanism. Methods AS models were constructed by oxidized low-density lipoprotein (ox-LDL)-treated VSMCs. Cell counting kit-8 for cell viability, wound scratch assay for cell migration, and flow cytometry for cell cycle, intracellular reactive oxygen species, and mitochondrial membrane potential (MMP) were performed. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels by biochemical kits, oxygen consumption rate (OCR) by seahorse apparatus, apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay (TUNEL) staining, and apoptosis-related expression by western blot were detected. Ras homolog gene family A/Rho-associated protein kinase-1 (RhoA/ROCK1) levels were measured by western blot and ELISA. The RhoA agonist, U46619, was employed to validate mechanism of THP. Results THP suppressed cell cycle progression and cell migration whereas alleviating cell viability and oxidative stress, as reduced MDA and enhanced SOD levels in ox-LDL-incubated VSMCs. THP protected mitochondrial function by higher MMP levels and OCR values. Additionally, THP decreased TUNEL-positive cells, Bax, Caspase-3, RhoA, ROCK1, and osteopontin expression, while increased Bcl-2 and smooth muscle myosin heavy chain levels. Furthermore, U46619 intervention antagonized effects of THP. Conclusion THP improved mitochondrial function in VSMCs of AS by inhibiting RhoA/ROCK1 signaling pathway.

Objective This study was to investigate the relationship between serum superoxide dismutase (SOD) and malondialdehyde (MDA) and arteriovenous fistula (AVF) maturation in maintenance hemodialysis (MHD) patients. Methods A total of 120 MHD patients were divided into a maturation group (72 patients) and a maturation failure group (48 patients). General information and ultrasound data were collected and venous blood was drawn for routine blood tests. General data and serum SOD and MDA were compared. Independent variables with statistically significant ( P < 0.05) differences in univariate analysis were included in multivariate logistic regression. Serum SOD and MDA in predicting maturation failure of AVF were analyzed using receiver operating characteristic curves. Results The internal diameter of the cephalic vein, internal diameter of the cephalic vein after tourniquet binding, internal diameter of the radial artery, and serum SOD level were lower and serum MDA level was higher in the maturation failure group. Reduced SOD and elevated MDA were independent risk factors for maturation failure of AVF. The area under the curve (AUC) for serum SOD and MDA was 0.68 each. When combined, their AUC for predicting AVF maturation failure was 0.79. Conclusion Reduced serum SOD and increased MDA are risk factors affecting AVF maturation in MHD patients.

Introduction Flavan-3-ols (FLs), astringent polyphenols, are known to have low bioavailability and induce excessive sympathetic nervous system activation. This study aimed to compare the effects of FLs on brown, subcutaneous, and visceral adipose tissue in mice. Methods C57BL/6J male mice fed a standard or high-fat diet were given water or 50 mg/kg FL orally by gavage for 2 weeks. Excised brown, inguinal, and epididymal fat tissues were prepared for frozen sectioning. After hematoxylin and eosin (HE) staining, the effects of FL administration on each adipose tissue were observed, and expression analysis of mitochondrial DNA genes was performed. Results Repeated administration of FL had no morphological effects on brown adipose tissue or visceral fat. However, FL significantly reduced the cell size in subcutaneous fat and induced the appearance of multilocular structures. Furthermore, FL increased cytochrome B expression in subcutaneous fat. The results showed that FLs induce browning of subcutaneous fat in mice. Conclusion This study showed that FL-induced enhancement of sympathetic nerve activity increased mitochondria in subcutaneous fat and promoted browning. However, no changes were observed in other adipose tissues. Further long-term administration is required to analyze the effects of FLs on adipose tissue thoroughly.

Objective This study aims to explore the current status of depression and related factors in middle-aged and elderly people in China using a cohort database with multi-year follow-up. Methods The study population for this project was derived from the China Health and Retirement Longitudinal Study. Participants were divided into control and depression groups based on scores from the Center for Epidemiological Research Depression Scale. Continuous variables were compared using t -tests or Mann–Whitney U tests, while categorical variables were compared using chi-square tests. A multivariate logistic regression model was employed to evaluate factors associated with depression. Results A total of 9,749 participants were included in the study. Correlation analyses revealed that age, body mass index, diastolic blood pressure, waist circumference, total cholesterol, uric acid, and length of sleep were significantly associated with depression ( p < 0.05). Women exhibited a higher risk of depression in middle and old age compared to men ( p < 0.05). An increase in waist circumference was associated with a decreased risk of depression ( p < 0.05). Longer sleep duration and higher educational levels were also associated with a reduced risk of depression ( p < 0.05). Unfavorable marital status and decreased frequency of alcohol consumption were found to increase the risk of depression ( p < 0.05). Conclusion In middle-aged and elderly individuals, women, low education level, and experiencing dissatisfaction in marriage are connected with a high risk of depression. On the other hand, increased waist circumference, moderate alcohol consumption, and longer sleep duration are connected with a low risk of depression.

Objective To explore the postoperative risk factors of Merkel cell carcinoma patients who have undergone surgical resection, and to construct a survival prognosis column chart. Method Patients diagnosed with Merkel cell carcinoma and underwent surgical resection from 2000 to 2019 were selected from the surveillance, epidemiology, and end results database. COX regression analysis was used to screen for independent prognostic factors, and a column chart was constructed. The predictive performance of the column chart was evaluated using consistency index, receiver operating characteristic curve, and calibration curve. Results The results of multi-factor COX regression showed that T stage and N stage were independent prognostic factors affecting cancer-specific survival (CSS) in patients after Merkel cell carcinoma resection. Construct a column chart based on the above two factors. The C-index of the column chart in the modeling group is 0.732 [95% CI (0.649, 0.814)], and the area under the curve (AUC) for the first and second years are 0.816 [95% CI (0.728, 0.904)] and 0.693 [95% CI (0.593, 0.792)], respectively. The C-index in the validation group was 0.724 [95% CI (0.569, 0.879)], and the AUC in the first and second years were 0.739 [95% CI (0.644, 0.833)] and 0.658 [95% CI (0.556, 0.759)], respectively. Conclusion The predictive model constructed based on two factors, T stage and N stage, has good prognostic diagnostic accuracy and is helpful for clinical decision-making and personalized treatment.

Objective Pancreatic cancer is distinguished by its high likelihood of metastasis and drug resistance, while the fundamental mechanisms are inadequately elucidated. This study aimed to identify pivotal hub genes associated with pancreatic cancer and assess their potential utility in predicting its onset and progression. Methods Weighted gene co-expression network analysis (WGCNA) combined with differential expression analysis identified novel susceptibility modules and hub genes for pancreatic cancer. Kyoto Encyclopedia of Genes and Genomes and gene ontology analyses were utilized to explore the potential roles of these hub genes. Receiver operator characteristic curves and nomogram models were developed to evaluate diagnostic efficacy. Mendelian randomization, flow cytometry, Transwell, and RNA sequencing were conducted to explore the association between C-X-C motif chemokine ligand 10 (CXCL10) and immune infiltration. Results WGCNA analysis was performed to build gene co-expression networks, and ten key genes were found. CXCL10 was the central gene, and its expression was significantly linked to the survival of patients with pancreatic cancer and their response to immune checkpoint inhibitors. CXCL10 demonstrated the ability to stimulate the differentiation of macrophages toward the M2 phenotype. CXCL10 could facilitate the metastasis of pancreatic cancer cells by modulating macrophage polarization. CXCL10 affects macrophage polarization by regulating the expression of vascular endothelial growth factor A. Conclusions CXCL10 demonstrates potential as a therapeutic target for managing pancreatic cancer.

Background Methylprednisolone is preferably used in acute traumatic spinal cord injuries but its efficacy is limited. The objectives of the study were to evaluate the efficacy and safety of preoperative intraperitoneal erythropoietin plus a high dose of methylprednisolone against a high dose of methylprednisolone monotherapy in patients with traumatic spinal cord injuries. Methods In the retrospective study, patients received preoperative intraperitoneal erythropoietin + intravenous methylprednisolone (EM cohort, n = 107) or methylprednisolone monotherapy (PE cohort, n = 140). Results The time between decompression surgeries and injuries was 34.58 ± 6.39 h/patient (maximum: 49 h). Neurologic and sphincter functions of patients at follow-up in the EM cohort exhibited better than the preoperative neurologic and sphincter functions in the same cohort and also neurologic and sphincter functions at follow-up in the PE cohort ( p < 0.05 for all). Higher 30-day postoperative mortality was reported in the PE cohort (43 (31%) vs 20 (19%), p = 0.0454) than those of the EM cohort. Conclusions: Preoperative intraperitoneal erythropoietin plus a high dose of methylprednisolone appears to have a beneficial neuroprotective effect, exhibited improved sphincter functions, and decreased mortality more than a high dose of methylprednisolone monotherapy in patients with traumatic spinal cord injuries who underwent surgeries.

Background The objective of this research was to investigate the involvement of RAB39B in acute myeloid leukemia (AML) using bioinformatics analysis and in vitro experiments for validation. Methods In this article, RNA sequencing data from The Cancer Genome Atlas and genotype-tissue expression were utilized to analyze the expression of RAB39BA and identify differentially expressed genes. Results AML exhibited elevated expression of RAB39B in diverse tumor types. In laboratory experiments, it has been demonstrated that RAB39B exhibits a significant expression level in AML cell lines when compared to normal peripheral blood monocytes. Moreover, RAB39B is closely linked to the growth and programmed cell death of AML cells. Conclusion In conclusion, RAB39B shows potential as a biomarker for the identification and prediction of AML, contributing to the growth and cell death processes in AML.

Background Peripheral conditioning induces transient ischemia, promoting antioxidant production in ischemia-affected tissues, which helps reduce heart reperfusion injury in ST-elevation myocardial infarction (STEMI) patients. This study compares troponin and creatine kinase-MB (CK-MB) levels among STEMI patients with and without remote conditioning. Methods This study included 160 patients treated for STEMI at a tertiary care centre. The study protocol involved cyclic inflation and deflation of a blood pressure cuff on the brachial region in four cycles of 5 min each. Markers of myocardial necrosis, CK-MB, and troponin, were monitored before percutaneous coronary intervention (PCI), immediately after, and at 24, 48, and 72 h post-PCI. Results CK-MB and troponin levels were significantly lower in non-diabetic patients who underwent remote peripheral conditioning compared to those who did not, with significant reductions observed after PCI (CK-MB: p = 0.001; troponin: p = 0.033), and at 24 (CK-MB: p = 0.015; troponin: p = 0.001) and 48 h post-PCI (troponin: p = 0.002). In the second phase, no significant differences in CK-MB or troponin levels were found between diabetic patients with and without conditioning. However, a trend toward lower values was noted in the conditioned group. In the third phase, significant reductions in CK-MB ( p = 0.002) and troponin levels (after PCI: p = 0.007; 24 h post-PCI: p = 0.045) were observed across all patients who underwent conditioning compared to the control group. Conclusion Peripheral pre- and post-conditioning is an economical, simple, and physiological method that effectively prevents and reduces heart damage caused by reperfusion injury, particularly in non-diabetic STEMI patients.

Objective The aim of this study was to explore the efficacy and safety of azacitidine (AZA) in middle-aged and elderly patients with myelodysplastic syndrome (MDS). Methods The clinical data of 59 middle-aged and elderly patients with middle- and high-risk MDS, who attended our hospital from April 2019 to January 2024, were retrospectively analyzed and were divided into an observation group (AZA) and a control group (conventional supportive treatment) according to the treatments, and the patients in the two groups were evaluated for their clinical efficacy and safety. Results The overall response rate of the observation group was 66.67%. In terms of blood cells, the observation group’s blood cell level after four courses of treatment was significantly higher than that of the control group ( P < 0.05). In terms of lactate dehydrogenase (LDH), the level of LDH decrease after four courses of treatment in the observation group was significantly better than that in the control group ( P < 0.05). The safety of both groups was good. Conclusions AZA is safe and effective in the treatment of high risk MDS in middle and old age patients.

Background Hypertension is a risk factor for cardiovascular disease. The present study aimed to explore the impact of ambulatory blood pressure load (BPL) on mitral regurgitation (MR) in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods A total of 215 CAPD patients hospitalized in the Department of Nephrology at the Fifth Affiliated Hospital of Sun Yat-sen University between November 2017 and June 2022 were included in the study. All subjects underwent 24-h ambulatory BP monitoring and an echocardiography examination. BPL and MR area (MRA) were calculated. Subjects were divided into high regurgitation group and non-high regurgitation group. General data were also collected. The effect of ambulatory BPL on MR in CAPD patients was analyzed using multiple linear regression. Results Baseline data comparison revealed statistically significant differences in hemoglobin, serum β 2 -microglobulin, NT-proBNP, left atrial diameter (LAD), left ventricular end-diastolic diameter (LVDD), LV ejection fraction (LVEF), LV fractional shortening (LVFS), and mitral valve calcification between the high and non-high regurgitation groups ( P < 0.05). There was no statistically significant difference in other clinical characteristics. Correlation analysis showed correlations between MRA and 24-h systolic BPL (24h-SBPL), 24-h diastolic BPL (24h-DBPL), daytime systolic BPL (D-SBPL), daytime DBPL (D-DBPL), nighttime systolic BPL (N-SBPL), nighttime DBPL (N-DBPL), hemoglobin level, NT-proBNP level, LAD, LVDD, LVEF, and LVFS. Multiple linear regression analysis revealed that the effects of 24h-DBPL and D-DBPL on MRA were statistically significantly different ( P < 0.05). Conclusions Ambulatory BPL, particularly 24h-DBPL and D-DBPL, significantly affected MR. Therefore, controlling BPL, especially DBPL, was essential for reducing the incidence of cardiovascular events and clinical mortality in CAPD patients.

Background Integrin subunit Alpha 3 is essential for cell adhesion and movement, but its role in breast cancer (BC) is unclear. This study evaluated ITGA3 expression in BC and its clinical significance. Methods The Human Protein Atlas (HPA), UALCAN, and Kaplan–Meier plotter were used to analyze ITGA3 in BC. ITGA3 was evaluated using receiver operating characteristic curves. The cell counting kit-8 test was used to examine the role of ITGA3 in cell proliferation. Results BC tissues’ ITGA3 protein and mRNA levels were significantly lower than normal controls. ITGA3 was associated with better recurrence-free survival (RFS) and distant metastasis-free survival, especially in estrogen receptor (ER)-positive, Luminal B, and Luminal B subtypes. ITGA3 predicted RFS for 5 years and the response to chemotherapy. ITGA3 was associated with ER status but not age, tumor, node, metastasis stages, or tumor size. ITGA3 has a positive impact on BC cell growth. Conclusions ITGA3 may be a predictive marker for BC and a therapeutic target. These findings need to be confirmed, and the molecular mechanisms of ITGA3 need to be clarified.

Introduction Diabetic kidney disease (DKD) represents serious diabetes-associated complications, and podocyte loss is an important histologic sign of DKD. The cellular and molecular profiles of podocytes in DKD have yet to be fully elucidated. Methods This study analyzed kidney-related single-nucleus RNA-seq datasets (GSE131882, GSE121862, and GSE141115) and human diabetic kidney glomeruli transcriptome profiling (GSE30122). ARHGAP28 expression was validated by western blot and immunohistochemistry. Results In human kidney tissues, 154 differentially expressed genes (DEGs) were identified in podocytes, which were enriched in biological processes related to nephron development and extracellular matrix–receptor interactions. Similarly, in the mouse kidney, 344 DEGs were found, clustering in pathways associated with renal development and signaling mechanisms like PI3K/Akt (phosphatidylinositol-3 kinase/protein kinase B) and PPAR (peroxisome proliferator-activated receptor). In diabetic human kidney glomeruli, 438 DEGs were identified, showing significant enrichment in pathways related to diabetic nephropathy. Venn analysis revealed 22 DEGs common across human and mouse podocytes and diabetic glomeruli, with ARHGAP28 being notably overexpressed in podocytes. The diabetic nephropathy model using db/db mice showed that ARHGAP28 expression was significantly upregulated in the kidney cortex and glomeruli. In vitro studies using a high-glucose podocyte model corroborated these findings. Conclusions Collectively, this study provides an insight into the function and diagnosis of DKD and indicates that ARHGAP28 in podocytes is a potential biomarker of DKD.

Objective To investigate the significance of the reverse shock index multiplied by the Glasgow Coma Scale score (rSIG) and the neutrophil–lymphocyte ratio (NLR) in the prediction of prognosis in patients with multiple injuries. Methods The clinical data of 142 patients with multiple injuries admitted to the Emergency Department of Shenzhen Longhua District Central Hospital between January 2019 and December 2022 were retrospectively analyzed. Subjects were divided into the survival group ( n = 102) and the deceased group ( n = 40) based on their survival status at 28 days after injury. We subsequently analyzed the intergroup differences in blood test results, rSIG, and NLR, as well as the relationship between rSIG and NLR. The predictive value of rSIG, NLR, and both combined in determining the prognosis of patients with multiple injuries was explored by plotting the receiver operator characteristic (ROC) curve. Based on the optimal cut-point value of the ROC curves, subjects were divided into groups with rSIG ≤ 7.75 (22 patients) and rSIG > 7.75 (120 patients), as well as groups with NLR ≤ 10.36 (104 patients) and NLR > 10.36 (38 patients), and the 28-day mortality rate was compared between the groups. Results A total of 142 patients were enrolled. The rSIG of the survival group ( n = 102) was significantly greater (15.7 ± 4.8) than that of the deceased group ( n = 40, 6.2 ± 2.9), ( t = 14.307, p < 0.001). The NLR of the survival group was higher than that of the deceased group, but the difference was not statistically significant ( p > 0.05). The area under the curve (AUC) of the ROC of NLR was significantly greater than that of rSIG (0.922 vs 0.54) ( Z = −7.881, p < 0.001). The AUC for NLR was also statistically greater than that of the combination of rSIG and NLR (0.963 vs 0.54) ( Z = −8.378, p < 0.001). The AUC of the combination of rSIG and NLR was significantly greater than that of rSIG (0.844 vs 0.540) ( Z = 2.239, p = 0.025). The 28-day mortality rate of patients in the rSIG ≤ 7.75 group was also significantly greater than that of patients in the rSIG > 7.75 group (10.0%) ( p < 0.05). Finally, the 28-day mortality rate in the group with an NLR ≤ 10.36 was lower than that in the group with an NLR > 10.36 ( p < 0.05). Pearson correlation analysis showed that the correlation coefficient between rSIG and NLR was r = 0.13, which did not reach statistical significance ( p = 0.12). Conclusion NLR, rSIG, and the combination of the two are all valuable in predicting the prognosis of patients with multiple injuries (all AUC > 0.5). However, the predictive capacity of NLR was better than either rSIG alone or both combined. These findings may serve as references in guiding the treatment of patients with multiple injuries in clinical practice.

Aim We examined marine collagen supplements derived from fish and jellyfish for the presence of toxic metals and metalloids (Pb, Cd, Cr, Hg, and As). A risk assessment was also carried out by converting the obtained concentrations into average daily doses (ADDs) and comparing them with tolerable daily intakes (TDIs) to evaluate potential health risks associated with long-term consumption. Methods The levels of Pb, Cd, Cr, and As in marine collagen samples were quantified using inductively coupled plasma mass spectrometry (ICP-MS). Mercury levels were analysed with a direct analyser. The study analysed various brands of marine collagen supplements from fish and jellyfish, ensuring compliance with EU regulatory limits. Results Arsenic was the most abundant element detected, with mean values of 0.59 ± 0.28 mg/kg, followed by Pb (0.13 ± 0.02 mg/kg). Significant variability was observed between brands. Hg was detectable in only 12% of the samples. Marine collagen samples derived from jellyfish and Scomber scombrus skin extract showed no detectable toxic metals or metalloids. None of the samples exceeded EU regulatory limits, and ADDs were consistently below TDIs, indicating safety for consumption at recommended doses. However, it is recommended that food safety regulations be updated to account for potential cumulative risks from simultaneous intake of contaminated supplements.

Purpose Marginal zone lymphoma (MZL) is a rare subtype of non-Hodgkin lymphoma, and its diagnosis primarily relies on pathological biopsy. The study aims to investigate the causal relationships between 41 inflammatory cytokines and MZL using a two-sample bidirectional Mendelian randomization (MR) approach, providing new insights and methodologies for rapid differential diagnosis and treatment strategies. Methods Causal associations between 41 inflammatory cytokines and MZL were examined using genetic variant data from two large-scale genome-wide association studies. The inverse variance weighting method was employed, and multiple sensitivity analyses, including MR-Egger, weighted median, simple model, and weighted model methods, were conducted to strengthen the robustness of the findings. Results Elevated levels of MIG and IL-10 were associated with an increased risk of MZL (MIG: OR = 1.57, p = 0.035; IL-10: OR = 1.69, p = 0.021), while higher B-NGF levels exhibited a protective effect (OR = 0.46, p = 0.027). Reverse MR analysis revealed a negative correlation between MZL and IFN-γ levels (OR = 0.97, p = 0.015). Conclusions MIG, IL-10, B-NGF, and IFN-γ are potential biomarkers and therapeutic targets for MZL. IFN-γ likely acts as a downstream molecule in MZL pathogenesis, offering novel insights into MZL-related research, clinical diagnosis, and treatment strategies.

Background and aim Knowing the gender beliefs (GB) that legitimize dating violence (DV) it is important for the prevention of this phenomenon. The aim is to evaluate the impact of GB interventions that legitimize DV. Methods Single group quasi-experimental study, with a sample of 148 Portuguese adolescents. A questionnaire was used to collect data, with data processing carried out using SPSS, using descriptive and inferential statistics. Results The interventions included an infographic on gender asymmetries, a video about DV, and posters on the topic and Health Education sessions. The largest group fell into the less conservative GB (40.5%) and the categories of non-violent relationship and considerably violent relationship had the same percentage (38.5%). The rank mean of the gender belief inventory scale before and after the interventions was, respectively, 35.24 and 33.06 points, while the same measurements of the violent youth relations inventory scale were 2.74 and 1.63 points. There were statistically significant differences (Wilcoxon: p = 0.01) between the GB score before and after the interventions, as well as in the violent youth relations (VYR) scale score (Wilcoxon: p = 0.000). Conclusion The interventions had a significant impact on reducing the GB legitimizing the DV and VYR, and were effective.

Objective To evaluate the effect of serum IL-6, C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) levels on the efficacy of modified preperitoneal Kugel repair in patients with inguinal hernia. Methods Clinical records of 42 patients with inguinal hernias who underwent modified preperitoneal Kugel repair were retrospectively analyzed. Serum IL-6, CRP, and MMP-9 were detected before surgery and after surgery. The patients were divided into the corresponding high-expression group and low-expression group. The basic data and clinical characteristics of patients were analyzed and compared, as well as postoperative indexes. Results In patients with inguinal hernia, serum IL-6, CRP, and MMP-9 increase first and then decrease after surgery, reaching the peak value around 24 or 48 h after surgery. Patients with high-expression of IL-6, CRP, and MMP-9 had longer hospital stays and time to return to normal activities, and were more likely to have chronic abdominal pain. In addition, high-expression of IL-6 and CRP had a higher probability of postoperative VAS values and wound infection, and high-expression of IL-6 and MMP-9 were also more likely to have wound healing injuries. Conclusions Serum IL-6, CRP, and MMP-9 levels in patients with inguinal hernia can affect the efficacy of modified preperitoneal Kugel repair and the prognosis of patients.

Background The number of studies on the effect of smoking cessation interventions in polycythemic patients is limited. Our aim was to examine the effects of quitting smoking on hematological parameters in patients with polycythemia and to evaluate the outcomes of smoking cessation interventions in polycythemic patients. Methods The prospective study was conducted in the hematology outpatient clinic between November 2022 and May 2023. Patients with polycythemia were grouped according to their smoking status. Smoking cessation interventions were applied to current smokers. Blood parameters were compared according to smoking status at the baseline and third month follow up. Results At first presentation, 65.4% ( N = 93) of 142 patients were current smokers and 34.5% ( N = 49) were non-smokers. Fifty-one percent ( N = 47) of active smokers quit smoking at the 3-month follow-up after the intervention. Hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume, very low density lipoprotein cholesterol, and immature granulocytes were found to be higher in active smokers compared to non-smokers at initial presentation ( p < 0.05). Hb and Hct values decreased in smokers who quit smoking compared to baseline values at 3 months ( p < 0.05). Conclusions Of the patients with polycythemia, 65% were current smokers and about half of them were successful in quitting smoking at 3 months with effective implementation of smoking cessation interventions.

Background Early and accurate diagnosis of pulmonary infection (PI) is crucial for the timely implementation of appropriate treatment strategies in lung cancer patients. Methods Metagenomic next-generation sequencing and conventional testing were performed in lung cancer patients with and without PI. The pathogen profiles were analyzed, and risk factors for PI were explored using univariate and multivariate logistic regression models. Results A total of 55 lung cancer patients with PI and 59 non-infected lung cancer patients were included. There were 41 underlying pathogens identified by both methods in lung cancer patients with PI. The coexistence of different pathogen types was common, particularly between fungi and viruses, which was observed in 28.57% of cases. The incidence of Streptococcus pneumoniae and Pneumocystis jirovecii is significantly higher in small-cell lung carcinoma patients compared to that in non-small-cell lung carcinoma patients. Besides, cytomegalovirus, P. jirovecii , and Aspergillus were more likely to be found in advanced-stage patients. Risk factor analysis revealed that Karnofsky Performance Status <90 and chemotherapy were strongly associated with PI in lung cancer patients. Conclusions This study highlights the complexity of PI in lung cancer patients, emphasizing the need for tailored diagnostic and therapeutic strategies based on cancer type and stage.

Background Paclitaxel (PTX) chemotherapy frequently induces cognitive impairment, which is closely associated with two key pathological processes: necroptosis of hippocampal neurons and microglial polarization. Necroptotic neurons release damage-associated molecular patterns, triggering inflammatory responses. As the primary immune cells in the central nervous system, microglia can exhibit either pro-inflammatory or anti-inflammatory activity depending on their polarization state. However, the relationship between PTX-induced neuronal necroptosis and microglial activation remains unclear. Methods In this study, both in vivo and in vitro experiments were conducted. In vivo , an adult male C57BL/6N mouse model of PTX-induced cognitive impairment was established and divided into three groups: Veh (vehicle control), PTX (paclitaxel only), and P + N (paclitaxel with Nec-1 treatment). Necrostatin-1 (Nec-1), a specific inhibitor of RIPK1, was used to inhibit necroptosis. In vitro , HT22 cells were used to prepare necroptosis-conditioned medium, and BV-2 cells were treated with this medium. TAK-242, a TLR4 inhibitor, was used to explore the role of the TLR4/MyD88 signaling pathway. Immunofluorescence staining, western blot, and ELISA were employed to detect relevant markers and cytokines. Results The results demonstrated that PTX-induced necroptosis of hippocampal neurons activated microglia. Nec-1 effectively suppressed neuronal necroptosis and reduced M1 polarization of microglia. The TLR4/MyD88 signaling pathway was involved in microglial polarization induced by the necroptotic-conditioned medium of PTX-treated HT22 cells. TAK-242 significantly blocked the regulatory effect of PTX-induced neuronal necroptosis on BV-2 microglial polarization. Conclusion This study reveals that hippocampal neuron necroptosis activates microglia through the TLR4/MyD88 signaling pathway in PTX-induced cognitive impairment, promoting M1 polarization and neuroinflammation. Inhibiting necroptosis promotes M2 polarization and neuroprotection. These findings uncover a novel mechanism of PTX-induced cognitive impairment and suggest potential therapeutic targets.

Appropriate formation of blood vessels is critical for tendon-bone healing during tendon injury, as excessive angiogenesis would exacerbate scar formation and lead to chronic pain and dysfunction. The mechanism to regulate inflammatory angiogenesis during tendon-bone healing remains to be elucidated. Here, we utilized lipopolysaccharide (LPS) to induce tenocyte inflammation and applied the conditioned medium from inflammatory tenocytes to treat rat aortic vascular endothelial cells (RAOECs). The results that indicated LPS treatment significantly induced the mRNA and protein upregulation of NLRP3, tumor necrosis factor α, IL-1β, and vascular endothelial growth factor A (VEGFA), as well as the secretion of VEGFA. Furthermore, the conditioned medium stimulated RAOEC angiogenesis. Celastrol, a quinone-methylated triterpenoid from Tripterygium wilfordii , has been reported to treat osteoarthritis. Here, celastrol could suppress LPS-induced upregulation of NLRP3 and IL-1β, and the secretion of VEGFA. Celastrol treatment also suppressed the conditioned medium-induced angiogenesis in RAOEC. Moreover, we established a rotator cuff tear rat model to stimulate tendon injury. Celastrol administration at the lesion significantly promoted tendon healing and functional recovery in injured mice by regulating NLRP3 and VEGFA levels. Taken together, these data suggest that the inflammation-induced tenocyte injury leads to angiogenesis, and that celastrol administration could suppress the inflammatory tenocyte-induced angiogenesis to promote tendon-bone healing via the NLRP3 pathway.

Background C5 nerve root palsy (C5P) is a rare but documented complication after cervical decompression surgery. Despite multiple proposed mechanisms, research on risk factors for C5P after anterior cervical discectomy and fusion (ACDF) remains insufficient. Objective The aim of this study was to identify specific risk factors associated with C5 nerve root palsy after ACDF. Methods A total of 108 patients who underwent ACDF surgery were divided into C5P and non-C5P groups. The basic data, preoperative Japanese Orthopaedic Association score, cervical curvature correction at C2–7 and C4–5, anterior–posterior diameter (APD) at C4/5, spinal-cord-lumbar angle (CLA) at C4/5, foramen magnum occipitalis at C4/5, and the presence of preoperative high-signal areas in the C4/5 spinal cord on T2-weighted magnetic resonance imaging, were present. Risk factors associated with C5P were identified using logistic regression analysis. Results There were no significant differences between the two groups in terms of age, gender, disease duration, diagnosis, preoperative Japanese Orthopaedic Association score, number of operated segments, APD, or high-intensity zone. LRA showed that a larger CLA and narrower FD at C4/5 were the main risk factors for the development of C5P ( P < 0.05). Conclusion A larger cord-lamina angle and a narrower foraminal diameter at C4/5 are significant risk factors associated with the development of C5 palsy following ACDF.

Objectives Diffuse large B-cell lymphoma (DLBCL) is a common and highly aggressive type of lymphoma. Iron metabolism plays a critical role in human diseases, however, which remains unclear in DLBCL patients. The study is to explore the genetic characteristics and molecular mechanisms underlying ferroptosis in DLBCL patients. Methods Based on the GEO, GeneCards database, weighted gene co-expression network analysis was performed on the DLBCL sample and iron metabolism-related datasets. Enrichment analysis (Gene Ontology/Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis) was used to analyze the expression and possible mechanism of key genes in DLBCL patients. The key genes were identified by quantitative real-time PCR. Results The results showed that GATA-binding factor 1 (GATA1), as a key gene of iron metabolism in DLBCL patients, was related to the myeloid cell differentiation and granulocyte differentiation pathways to affect CD4 + T cells, B cells, and monocytes. GATA1 was strongly positively or negatively correlated with sensitivity to multiple targeted drugs. The patients with high GATA1 expression had shorter overall survival and worse prognosis than the patients with low expression. Additionally, high expression of the GATA1 gene was confirmed in DLBCL patients. Conclusions GATA1 as one of the important genes of ferroptosis suggested a significant biomarker for predicting the prognosis of DLBCL patients.

Objectives To evaluate the factors associated with false lumen thrombosis in preoperative type B aortic dissection (TBAD) patients. Methods Between January 2008 and December 2017, TBAD patients were evaluated. Participants were divided into patent, partial thrombosis, and complete thrombosis groups according to the status of the false lumen. Univariate analysis and logistic regression analysis were used to identify the factors associated with false lumen thrombosis. Results A total of 285 participants fulfilled our inclusion criteria. Patients in the complete thrombosis group were significantly older than those in the partial thrombosis and patent groups (59 ± 10 vs 53 ± 11 and 50 ± 11 years, respectively), and combined shorter dissection lengths (290 ± 101 vs 354 ± 92 and 351 ± 102 mm, respectively). The following factors were associated with partial thrombosis of the false lumen with an odds ratio (OR) <1: primary tear size (OR, 0.96; 95% confidence interval [CI], 0.93–0.99; p = 0.03), last tear size (OR, 0.93; 95% CI, 0.87–0.99; p = 0.04), and the total number of tears (OR, 0.87; 95% CI, 0.78–0.98; p = 0.02). Conclusions TBAD patients older than 59 years or with aortic dissection lengths of less than 290 mm were more likely to have a thrombosed false lumen.

Background The immune microenvironment of ovarian cancer is crucial in its progression. Recent studies highlight the significant role of MZB1 in shaping the tumor immune microenvironment (TIME), although its specific function in ovarian cancer remains unclear. Materials and methods We analyzed 381 ovarian cancer samples from the TCGA database, along with additional samples from GEO and single-cell datasets. Differentially expressed genes (DEGs) were identified using DESeq2. Various algorithms were applied to assess the relationship between MZB1 and the TIME. Cell proliferation was measured using the CCK-8 assay, while cell migration was evaluated using the wound healing assay. Furthermore, a nomogram predicting overall survival was developed based on multivariable Cox regression results. Results Our results indicated a positive correlation between high MZB1 expression and improved clinical prognosis. Additionally, higher MZB1 expression was linked to increased immune cell infiltration within the TIME. Elevated MZB1 levels inhibited the migration and proliferation of SKOV3 cells. The nomogram’s C-index was 0.702, and its calibration curve demonstrated good calibration, indicating satisfactory discrimination and accuracy in predicting patient outcomes. Conclusions This study comprehensively analyzes MZB1’s role in the TIME of ovarian cancer. MZB1 is a promising prognostic marker and a potential target for personalized treatment. Graphical abstract

Background Dioscin (Dio) is an important anti-tumor active component found in the seeds of Livistona chinensis . However, the efficacy and mechanism of Dio in relation to the progression of glioblastoma (GBM) remain unclear. Materials and methods Using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays, flow cytometry, and Hoechst staining in vitro experiments. A tumor-bearing nude mouse model was employed to further explore the impact of Dio on GBM tumor growth in vivo experiments. Using network pharmacological analysis and molecular docking to predict the potential target proteins and signaling pathways of Dio anti-GBM. The expression of proteins associated with apoptotic pathways was assessed by western blotting. Results Dio effectively suppresses the proliferation and promotes apoptosis of U251 cells. In the established tumor-bearing nude mouse model, the anti-cancer activity of Dio was further assessed. Kyoto Encyclopedia of Genes and Genomes enrichment analysis highlighted cancer signaling pathways, including epidermal growth factor receptor (EGFR). Western blot results showed that EGFR phosphorylation and apoptosis gene CASP3 increased with the increase of Dio concentration. Conclusions Dio could inhibit the proliferation and promote apoptosis of GBM cells, and play a significant inhibitory role in tumor growth. Dio could affect the phosphorylation of EGFR and then trigger the apoptosis process, resulting in the up-regulation of apoptosis protein CASP3 expression in GBM cells.

Background Twin pregnancies are associated with a higher risk of perinatal mortality compared to singleton pregnancies. This study evaluated the developmental trends and summarized the key features of research on preterm births in twin pregnancies. Methods A bibliometric analysis was conducted using publications on preterm births in twin pregnancies from 2014 to 2023, retrieved from the Web of Science Core Collection database. Network and visual analyses were performed using VOSviewer and CiteSpace software. In total, 1,378 articles were included. Results The number of publications in this field has shown a steady increase over the past decade. The United States, China, and England collectively contributed more than half of all publications. King’s College London, Columbia University, and Jefferson University were identified as the most influential institutions, fostering extensive collaboration and academic exchange. Am J Obstet Gynecol emerged as the most cited journal. Research has predominantly focused on clinical practices, including prevention strategies, risk factor identification, and perinatal outcomes. Conclusion This bibliometric analysis offers a comprehensive overview of research trends on preterm births in twin pregnancies, highlighting major contributors, influential institutions, and primary research foci. The findings provide valuable insights for researchers, aiding the identification of future research directions in this critical field.

Objective The aim of this study was to investigate the feasibility of the 4-week IgE/baseline IgE ratio and tryptase to predict the clinical efficacy of omalizumab in the treatment of pediatric moderate-to-severe asthma. Methods Moderate-to-severe asthma patients were selected, and their baseline IgE levels were recorded, and the IgE levels were tested again after 4 weeks of treatment with omalizumab to calculate the 4-week IgE/baseline IgE ratio. Serum tryptase was measured. Treatment efficacy was assessed. Patients were divided into response and non-response groups. Receiver operating characteristic curves were plotted for the sensitivity and specificity of the indices in predicting response to omalizumab treatment. Results Serum total IgE levels increased to 655.89 IU/mL, serum tryptase was 5.31 ng/mL after 4 weeks of treatment, which was higher than at baseline. There was a significant difference in total serum IgE between children in response and non-response groups after 4 weeks of treatment. The response group children had a higher 4-week IgE/baseline IgE ratio, whereas tryptase was lower. Combined metrics had moderate predictive value for the efficacy of omalizumab therapy. Conclusion The 4-week IgE/baseline IgE ratio combined with tryptase can predict, to a certain extent, the clinical efficacy of omalizumab in the treatment of pediatric moderate-to-severe asthma.

Background Peripheral nerve injury can lead to sensory, motor, and autonomic nerve dysfunction, significantly impacting patients’ quality of life. Schwann cells (SCs), as key components of the peripheral nervous system, play a crucial role in nerve repair. However, many functionally specialized and flexible SC subtypes remain unidentified. Recent advancements in single-cell transcriptomics have enabled a deeper understanding of SC heterogeneity during peripheral nervous system development. Methods In this study, we utilized single-cell transcriptomics to investigate SC heterogeneity in the dorsal root ganglia of both normal and spinal nerve injury mouse models. Results We identified a novel SC subtype associated with pressure sensation, which we termed stress response related SCs (SRSCs). These cells are terminally differentiated and highly express the pressure-sensing gene Npy . Following peripheral nerve injury, SRSCs function as stimulus receptors, receiving external stimuli and transmitting signals to typical repair SCs via the SPP1 signaling network. This interaction promotes dedifferentiation and facilitates injury repair. Conclusion Our findings enhance the understanding of SC heterogeneity and reveal SRSCs as key players in nerve repair. These insights provide potential targets for developing novel therapeutic strategies for peripheral nerve diseases.

Objective We explored the causal relationship between pancreatitis and various autoimmune diseases using bidirectional Mendelian randomization (MR). Methods We collected genome-wide association study summary data for four pancreatitis types and five autoimmune diseases to conduct our bidirectional MR analysis. The primary analysis was performed using the inverse variance weighted (IVW) method, complemented by MR Egger, weighted median, and weighted mode methods. Sensitivity analyses included Cochran’s Q test for heterogeneity, MR-Egger regression for pleiotropy, and MR-PRESSO and leave-one-out analyses for outliers. Results The result of IVW revealed a significant association between genetically predicted inflammatory bowel disease (IBD) and an increased risk of acute pancreatitis (AP) (odds ratio [OR] = 1.07, 95% confidence interval [CI] = 1.03–1.12, P = 0.0015). Subsequent analyses further confirmed this association in IBD subtypes, with genetically predicted ulcerative colitis (UC) and Crohn’s disease (CD) also showing increased risks of AP (UC: OR = 1.07, 95% CI = 1.02–1.13, P = 0.01; CD: OR = 1.05, 95% CI = 1–1.09, P = 0.03), affirming IBD as a risk factor for pancreatitis. Reverse analysis ruled out reverse causality and did not find a causal relationship between other immune diseases and pancreatitis. Conclusion These findings suggest that pancreatitis in IBD patients may arise from the disease itself, necessitating increased vigilance for AP during diagnosis and treatment.

Objective This study investigates the effects of subclinical doses of esketamine on serum NLRP3 levels and early cognitive dysfunction in elderly ischemic stroke patients after neurointerventional procedures under general anesthesia. Methods A prospective cohort study included 120 elderly ischemic stroke patients undergoing general anesthesia from January 2022 to September 2023. The esketamine group received 0.25 mg/kg of esketamine. Serum levels of NLRP3, C-reactive protein, interleukin-6 (IL-6), IL-1β, and IL-17 were measured before surgery and 24 h postoperatively. Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE). Results At 24 h postoperatively, the esketamine group had significantly higher MMSE scores ( p < 0.05) and lower serum levels of NLRP3, IL-17, and IL-6. Pearson’s correlation showed a link between NLRP3 levels and cognitive outcomes. Logistic regression identified heart rate, mean arterial pressure, preoperative NLRP3, IL-6, IL-17, and esketamine treatment as risk factors for cognitive dysfunction. Conclusion Subclinical doses of esketamine might reduce postoperative cognitive dysfunction risk and offer neuroprotection, presenting potential therapeutic options for elderly ischemic stroke patients.

Oral cancer constitutes a significant public health challenge, and gaining insights into the pathogenesis of oral cancer is crucial for the development of innovative therapeutic approaches. To address this objective, this study investigates the impact of interleukin-37 (IL-37) on oral cancer and its underlying mechanisms. Two oral cancer cell lines, HN13 and HSC-6, were employed in the study. Our findings reveal that IL-37 markedly inhibits cell viability and induces apoptosis in oral cancer cells. IL-37 attenuates the proliferation of oral cancer cells induced by lipopolysaccharide and tumor necrosis factor-alpha, while knockdown of IL-37 exacerbates this induction. Furthermore, IL-37 demonstrates anti-inflammatory effects on oral cancer cells. The modulation of inflammation, proliferation, apoptosis, and migration by IL-37 is mediated through the STAT3 pathway. The outcomes of this study contribute valuable insights to a deeper understanding of oral cancer pathogenesis and pave the way for the development of novel drugs for the treatment of this disease.

Background This study explores the factors related to the expression levels of carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA) and their association with poor postoperative prognosis in patients with esophageal squamous cell carcinoma (ESCC) who underwent minimally invasive resection. Methods Eighty patients with ESCC who underwent minimally invasive surgery were divided into two groups: 40 with poor prognosis (recurrence) and 40 with good prognosis (no recurrence). Additionally, 80 healthy subjects were selected as a control group. Serum CA199 and CEA levels were measured before surgery and 3 and 6 months postoperatively. Results The serum CA199 and CEA levels in the experimental group were significantly higher than in the control group ( P < 0.05). Patients with poor prognoses within the experimental group had higher CA199 and CEA levels than those with good prognoses ( P < 0.05). In the poor prognosis group, CA199 and CEA levels at 6 months were significantly higher than at 3 months post-surgery ( P < 0.05). Conclusion Poor prognosis in ESCC patients after minimally invasive resection may be influenced by factors such as lymph node metastasis, lesion length, and tumor location. Elevated CA199 and CEA levels postoperatively can serve as predictors of poor prognosis in patients with ESCC.

Purpose This work aimed to evaluate and analyze the efficacy and safety of modified drainage and catheterization in the treatment of cerebrospinal fluid leakage (CSFL) after posterior spinal surgery. Methods A total of 12 patients with CSFL were selected from June 2020 to June 2023. The modified drainage technique was used to treat CSFL. The perioperative index, including the duration of drainage tube placement, was observed. The study also assessed the amount of cerebrospinal fluid (CSF) drainage, the healing time of the drainage wound, the occurrence of other complications, the effectiveness of the drainage procedure, and the length of hospital stay. Results Among the patients with CSFL, the mean drainage time was 6.2 ± 0.8 days, the healing time of the drainage wound was 9.6 ± 1.7 days, and the hospital stay was 7.5 ± 1.0 days. The total volume of CSF drainage was 488.6 ± 55.3 mL. Furthermore, no cases of retrograde infection, drainage orifice exudate, or drainage wound nonunion were reported in this study. Conclusion This preliminary study demonstrates that the modified catheterization technique is effective in reducing the duration of CSFL and promoting rapid wound healing. Additionally, the novel drainage catheter shows advantages in terms of reducing the incidence of infection and other related complications.

Background This study comprehensively analyzes the pharmacological effects of ethanolic extract of Apteranthes tuberculata (EEAT) on various physiological parameters in mice. Objective The research aimed to quantify flavonoid and phenol contents across different extraction methods, with a focus on the superior efficacy of the ethanolic extract. Methods In vitro assays were conducted to assess the antioxidant activity of EEAT, revealing dose-dependent effects and significant inhibition percentages. Results EEAT exhibited notable analgesic effects in the writhing response test, particularly at 200 mg/kg, indicating its potential as a natural analgesic. Additionally, its anti-inflammatory effects were complex and dose-dependent in a carrageenan-induced paw edema model. The extract also showed significant changes in body temperature regulation following Brewer’s yeast-induced fever, revealing a distinct pattern of initial hypothermia followed by gradual re-elevation. Furthermore, EEAT demonstrated regulatory effects on gastrointestinal motility, with higher doses enhancing intestinal transit in charcoal meal tests. Conclusion This study highlights the pharmacological potential of EEAT as a natural therapeutic agent for antioxidant, analgesic, anti-inflammatory, and gastrointestinal regulation, warranting further investigation into its mechanisms of action and therapeutic applications.

Background Despite the high prevalence and serious clinical implications of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM), the relationship between glycemic control and CAD is usually overlooked. This study aimed to explore the relationship between time in range (TIR), a surrogate marker for glycemic control, and CAD in patients with T2DM. Methods Overall, 334 patients with T2DM were included and analyzed in this cross-sectional study. The presence of CAD was determined angiographically and the Gensini score was applied to evaluate CAD severity. TIR was calculated from sensor glucose from continuous glucose monitoring. Multivariable-adjusted logistic regression analysis was used to evaluate the relationship between TIR and CAD presence. Results T2DM with CAD had significantly lower TIR than those without (75.68 ± 13.74 vs 66.12 ± 11.87, P < 0.01). Moreover, TIR was correlated with CAD severity as indicated by the Gensini score. Multivariable-adjusted logistic regression analysis indicated that a higher TIR was an independent protective factor for CAD in patients with T2DM (OR = 0.919, 95% CI: 0.896–0.942). Conclusion TIR is significantly and independently related to CAD severity in T2DM patients. Thus, TIR could be a promising biomarker for the noninvasive assessment of CAD presence and severity in T2DM.

Background Prenatal alcohol exposure causes fetal alcohol spectrum disorders (FASD), primarily through alcohol-induced apoptosis. This study explores the link between ethanol-induced neuronal apoptosis and neural network electrical activity in developing rat retinal ganglion cells, and examines dopamine’s protective effects and influence on this activity. Methods The study employed a combination of immunohistochemical techniques, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and electrophysiological recordings to assess neuronal apoptosis and neural network activity in the developing rat retinal ganglion cell layer. Ethanol exposure was administered to model prenatal alcohol exposure, and dopamine was applied to evaluate its protective effects. Results Ethanol exposure was found to disrupt the spatiotemporal properties of synchronized spontaneous neural network electrical activity and partially induce neuronal apoptosis. Conversely, dopamine treatment increased the frequency of neural network electrical activity and attenuated ethanol-induced apoptosis. Conclusion The findings suggest that ethanol disrupts neural network activity and induces apoptosis in the developing nervous system, while dopamine exerts a protective effect by modulating neural network activity and reducing apoptosis. These results contribute to understanding the mechanisms underlying FASD and offer potential therapeutic avenues for prevention and treatment.

Objective To investigate the correlation between albumin levels during the third trimester and the risk of postpartum levator ani muscle rupture. Methods A retrospective analysis of 410 parturients undergoing vaginal delivery at Zhangzhou Hospital Affiliated to Fujian Medical University was conducted. Parturients were classified into low-albumin (<35 g/L) and normal-albumin (≥35 g/L) groups based on their albumin levels during the third trimester. Data on levator ani muscle rupture and various clinical parameters were collected and analyzed using multivariate binary logistic regression. Results The low-albumin group comprised 38.29% of participants and had a significantly higher incidence of levator ani muscle rupture (53.50%) compared to the normal-albumin group (33.20%; P < 0.05). Albumin levels strongly correlated with rupture risk ( r = 0.193, P < 0.001). Multivariate analysis showed low albumin levels were an independent risk factor (OR = 2.286, 95% CI: 1.259–4.152). Other independent risk factors included forceps-assisted delivery, BMI ≥ 24 kg/m², age ≥ 35 years, and second stage of labor duration ≥ 120 min (all P < 0.05). Conclusion Decreased albumin levels are an independent risk factor for postpartum levator ani muscle rupture, suggesting a potential role in increasing the risk of muscle injury.

Background This study was designed to address factors associated with maternal attention and distraction during breastfeeding and childcare and the role of smartphones in western Iran. Methods This cross-sectional study was conducted among 280 breastfeeding mothers in Iran in 2024. The data collection tools included a demographic-obstetric questionnaire and the Maternal Distraction Questionnaire. Data were analyzed using SPSS software, version 16, and the significance level was set less than 0.05. Results The highest distraction during breastfeeding was associated with mobile phone use (62.14%), while the lowest was linked to reading (6.78%.). Mobile phone use was the highest distraction during breastfeeding and baby care (79.64%), while the lowest was reading a book (12.86%). Additionally, individual and social variables, such as education level, number of children, and economic status, were significantly associated with maternal attention and distraction levels ( p < 0.05). Conclusion Distraction during breastfeeding and during child care between women with three or more children was higher compared with women with one child. Additionally, distraction during child care between women with three or more children was higher compared with women with two children.

Purpose Metabolic dysfunction-associated steatosic liver disease (MASLD) poses a global health challenge with limited therapeutic options. Hesperetin, a flavonoid extracted from citrus, exhibits multiple pharmacological properties, but its mechanisms in MASLD-associated lipid metabolism remain unclear. This study aimed to explore the mechanism of hesperetin for treating MASLD. Methods Network pharmacology identified the therapeutic targets for MASLD. Key targets were selected based on network topology analysis. Subsequently, Kyoto Encyclopedia of genes and genomes (KEGG) pathways and gene ontology enrichment were conducted. Molecular docking was performed to evaluate the binding affinity between hesperetin and the identified key targets. In vitro validation included lipid accumulation assays and verification of core target modulation via western blotting. Results Hesperetin significantly attenuated lipid accumulation in free fatty acid -induced HepG2 cells. Forty core targets of hesperetin for MASLD mitigation were identified. Notably, MYC, IL-6, IL1B, and PTGS2 had high network association values. KEGG analysis revealed predominant involvement in cancer-related pathways, non-alcoholic fatty liver disease, and JAK/STAT signaling. Biological processes included inflammatory response regulation and cytokine activity. Molecular docking confirmed strong hesperetin-IL-6 binding. Experimental data suggested that hesperetin may ameliorate lipid accumulation by modulating the IL-6-mediated STAT3-SOCS3 signaling pathway. Conclusion Hesperetin may ameliorate MASLD by targeting the IL-6-STAT3-SOCS3 axis, underscoring its therapeutic potential.

Introduction Italy’s oncological oblivion law codifies the right for cancer survivors to choose not to disclose their medical history under certain conditions, after 10 years from the end of treatment, or 5 years if diagnosed under the age of 21, in order to prevent discrimination in social, work, and professional opportunities. Materials and methods This article compares Italy’s law with other European countries’, aiming to analyze its implementation 1-year post-enactment and its medicolegal implications. Official sources and research from platforms like Google Scholar and PubMed were used. Results Oncological oblivion was first mentioned in the EU’s General Data Protection Regulation and further emphasized in the European Parliament’s 2020 resolution. Italy’s Law No. 193, enacted on December 7, 2023, aligns with constitutional principles to ensure freedom and equality for cancer survivors. Discussion Balancing privacy rights with collective security is crucial, especially in high-risk professions or insurance, where data concealment could raise ethical and legal issues. Conclusions In conclusion, while the initiatives implemented thus far are cutting-edge, there is an increasing necessity for more effective protection of the rights to privacy, self-determination, and psychological support to stave off patient discrimination. This is essential to ensure true equality among insured individuals.

To analyze the impact of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), and body mass index on the prognosis of colorectal cancer patients and to assess their clinical value. This cohort study included patients who underwent radical resection (R0 resection) for colorectal cancer. Peripheral blood laboratory test results for all patients were obtained within 1 week prior to surgery for the calculation of the NLR, PLR, and PNI. A total of 201 patients were included in the analysis. A total of 19 patients experienced relapse, and 30 patients died. The median follow-up duration was 39.2 months. Receiver operating characteristic curve analysis indicated that the PNI demonstrated moderately high predictive accuracy for overall survival (OS), with an area under the curve of 67.31%. After stratification based on the cutoff value, patients with a PNI of ≥44.48 exhibited a better survival prognosis than those with a PNI of <44.48 ( P = 0.001). However, according to the univariate Cox regression analysis, the PNI was significantly associated with OS (hazard ratio: 0.29; 95% confidence interval: 0.14–0.62; P = 0.001). The PNI, rather than the NLR or PLR, exhibited better predictive performance. After classifying patients based on the PNI cutoff value, patients with a high PNI had better survival outcomes.

Objectives The aim of the study was to examine peripheral oxygen saturation values in the index and middle fingers of the dominant hand in healthy young adults measured while lying in a supine position or sitting straight up. Methods This study was a non-randomized and non-controlled, quasi-experimental repeated measures study. It was conducted with 200 healthy young adults in Turkey. A pulse oximeter was located at the same time on the index and middle fingers of the active hand of each participant while sitting upright, and after being kept there for 1 min, the results of the measurements were recorded. Later, the participants were brought into a supine position, and after 10 min of rest, measurements with a pulse oximeter placed on the index and middle fingers of the active hand were repeated in the same way. Results The mean age of the participants was 20.4 ± 1.8 years; 76.5% were female, and their mean body mass index was 22.5 ± 3.6 kg/m 2 . It was found that when the individuals were sitting upright, the peripheral oxygen saturation values measured from the middle finger were significantly higher than the peripheral oxygen saturation values measured from the middle finger in the supine position ( p = 0.003). It was found that the peripheral oxygen saturation values of female participants measured from the index finger in the upright sitting position and from the index and middle fingers in the supine position were significantly higher than the saturation values of male participants ( p = 0.018, p < 0.001, p = 0.001, respectively). In addition, it was found that the peripheral oxygen saturation values measured from the index and middle fingers of underweight individuals in the sitting position and from the index and middle fingers in the supine position were significantly higher than the saturation values of overweight individuals ( p = 0.021, p = 0.006, p = 0.001, respectively). Conclusion In the conclusions of this study, it was found that the highest oxygen saturation value of the young adults was measured from the middle finger when they were in the upright sitting position. It was also found that the variables of gender and body mass index significantly affected the peripheral oxygen saturation value.

Background and aim Hysteroscopy is the gold standard for diagnosing endometrial and cervical canal pathology and can be used alone or in combination with other methods. The study aimed to compare abnormal findings of vaginal color Doppler ultrasonography (transvaginal sonography [TVS]) and hysteroscopy. Methods This study involved 100 infertile women with a history of two or more failed implantations of in vitro fertilization (IVF) from January 2020 to January 2021 in the infertility ward of Al-Zahra Hospital in Tabriz, Iran. All patients underwent hysteroscopy and TVS in the follicular phase to examine the endometrial cavity. We calculated the sensitivity and agreement of TVS color Doppler compared to hysteroscopy and using appropriate statistical tests. Results The overall proportion of abnormal findings was 69 and 66% through hysteroscopy and TVS. The sensitivity and kappa statistics of TVS compared to hysteroscopy were 95.6 and 93.2%, respectively. Endometrial polyps were the most common abnormalities in hysteroscopy (31%) and TVS (25%). In examining the relationship between hysteroscopy findings and vaginal color Doppler ultrasonography findings, a significant association was found between submucosal myoma and non-homogeneous myometrium (OR = 1.8 (1.02–5.3); P = 0.027), endometrial polyps and non-homogeneous myometrium (OR = 2.7 (1.04–7.4); P = 0.025), intrauterine adhesion and uterine artery PI (OR = 1.9 (1.3–8.2); P = 0.001), endometrial atrophy and endometrial thickness (OR = 2.4 (1.01–4.5); P = 0.034), and thick/irregular endometrium and adenomyosis (OR = 2.5 (1.4–15.9); P = 0.001). Conclusion Abnormal findings of hysteroscopy and TVS were observed more in patients who have a history of two or more unsuccessful IVFs. Comparing and evaluating the relationship between them can be considered a positive prognostic factor and a better diagnosis for achieving pregnancy in the IVF procedure in women with a history of recurrent implantation failure.

Background and aim Stroke patients with low levels of walking independence often experience persistent deficits in gait and balance, which significantly limit their functional mobility and quality of life. Robotic-assist gait training (RAGT) has emerged as a promising intervention to promote motor recovery and improve postural control in this patients. While previous studies have demonstrated the benefits of RAGT, few have directly compared the effects of fixed end-effector type and mobile robotic gait devices in patients with severely impaired ambulation. This study aimed to investigate and compare the effects of these two robotic gait training on balance and lower extremities motor recovery in stroke patients classified as functional ambulation category 0 to 2. Methods Twenty-eight stroke patients were randomly assigned to either end-effector or mobile robot groups, undergoing 12 weeks of therapy with one daily robotic session and seven conventional physical therapy sessions per week. Outcomes were measured using the Berg Balance Scale (BBS) and Fugl–Meyer Assessment for Lower Extremity (FMA-LE), with subcategory analysis for reflex activities, volitional movement within synergies, volitional movement mixing synergies, volitional movement with little or no synergy, normal reflex activity, and coordination/speed. Results Both groups showed significant improvements in BBS and FMA-LE, with the mobile robot group showing greater gains. Both groups improved in walking independence, though no significant difference was found between them. Subcategory analysis showed improvements in reflex activities and coordination/speed in both groups, but volitional movement within synergies and volitional movement with little or no synergy improved only in the mobile robot group. Correlation analysis revealed significant relationships between FAC and BBS, and BBS and reflex activities. Volitional movement within synergies and volitional movement mixing synergies had high correlations with motor recovery. Conclusion Both robotic methods effectively improved balance and motor recovery, with mobile robots showing greater potential for enhancing functional autonomy.

Background Previous research has indicated a possible association between asthma and ankylosing spondylitis (AS). Methods We pinpointed single nucleotide polymorphisms linked to various forms of asthma and AS, employing them as instrumental variables for a bidirectional two-sample Mendelian randomization (TSMR) analysis. Our TSMR analysis focused on European populations to minimize racial confounding. Multivariate adjustments for body mass index (BMI), smoking, and alcohol use were performed to control for confounders. Colocalization analysis was used to validate MR findings and explore genetic links between asthma and AS. Results Individuals with asthma and eosinophilic asthma exhibited a relatively higher risk of AS (asthma: OR 1.31, 95% CI 1.07–1.62, P = 0.008; eosinophilic asthma: OR 1.24, 95% CI 1.005–1.544, P = 0.044). Allergic asthma, childhood-onset asthma, and obesity-related asthma showed no causal relationship with AS (allergic asthma: IVW P = 0.27; childhood-onset asthma: IVW P = 0.66; obesity-related asthma: IVW P = 0.53). After adjusting for cigarette smoking, alcohol consumption, and BMI, the results supported a direct causal effect of asthma on the increased risk of AS onset (IVW P = 0.001). Conclusion This study revealed that a positive causal connection between asthma, specifically eosinophilic asthma, and AS.

Background Investigated the relationship between health literacy and treatment adherence and compliance due to incorrect medication use resulting from low health literacy in southern Taiwan. Methods A cross-sectional study in Chiayi, Taiwan (Sep–Nov 2013) used randomized sampling to survey 300 adults. Health literacy was assessed via the test of functional health literacy in adults, and medication knowledge/behavior was assessed via a validated questionnaire (KR-20 = 0.83). Data were analyzed using SPSS (chi-square, t -tests, ANOVA, Pearson’s correlation, P < 0.05). Results It was found that 97.9% of the respondents had adequate health literacy. Age negatively correlated with health literacy ( r = –0.395; P < 0.0001) and positively with medication knowledge ( r = 0.121; P = 0.038). Women exhibited higher health literacy and medication knowledge than men. Higher education levels and living with health professionals were associated with better health literacy. Patients with chronic diseases had lower health literacy than those without (mean scores: 31.5 vs 32.7). Significant correlations were observed between health literacy and treatment adherence and compliance and use. Conclusions Targeted health literacy interventions are required across different ages, genders, and education levels to improve medication use and health outcomes. Future research should examine the long-term effects of these interventions.

Objective This study was to investigate the correlation between serum calprotectin (Cal) and the severity and outcome of patients with acute cerebral infarction (ACI). Methods Clinical data and serum Cal data were collected from 160 ACI patients and 60 healthy individuals. ACI patients were grouped according to their prognosis. Clinical data, biochemical indicators, and Cal levels were measured. Correlations between serum Cal and National Institute of Health stroke scale (NIHSS) scores, Glasgow Coma Scale (GCS) scores, and hematocrit (HCT) were analyzed. Results In ACI patients, elevated serum Cal levels were observed. These levels were positively correlated with NIHSS scores and inversely correlated with GCS scores and HCT. The receiver operating characteristic curve showed that serum Cal had an area under the curve of 0.770 for predicting poor outcomes, with a diagnostic cutoff of 18.01 mg/L. Serum Cal levels over 18.01 mg/L were independently related to poor prognosis for ACI and were identified as an independent risk factor for adverse outcomes. Conclusion Serum Cal shows high expression in patients with ACI. Serum Cal has a good predictive value for the outcome of ACI.

Objective To compare the diagnostic effects of computed tomography (CT) and bronchoscopy guided biopsy on pulmonary nodules. Methods “Subject words + free words” were used to search four literature databases including Pubmed, Embase, Cochrane Library, and Web of Science. The subject words were CT, bronchoscope-guided biopsy, pulmonary nodules, and diagnosis. The search is up to August 25, 2023. The retrieved literature was screened, and the literature with duplicate, review, incomplete data or article content and inconsistent with our research was deleted. Revman 5.4 was used for bias analysis of the literatures included in the analysis, and forest map, funnel map, and ROC curve were drawn to compare the accuracy, specificity, and sensitivity of the two diagnostic methods. Results A total of 2,622 articles were retrieved, and 8 articles were included in the study after screening. Bias analysis and funnel plot showed that eight included articles had higher quality and smaller bias. The sensitivity and specificity of the forest map were both 95% CI, and the sensitivity of CT diagnosis was better than that of bronchoscopy diagnosis, with similar specificity between the two groups. The funnel plot shows some heterogeneity in the literature on pulmonary nodules. The ROC curve shows that CT diagnosis is significantly superior to bronchoscopy diagnosis, with diagnostic accuracy approaching 100%. Conclusion CT has significant advantages in detecting and diagnosing pulmonary nodules, as it can detect nodules in various parts of the lungs. However, bronchoscopy has significant advantages in diagnosing small pulmonary nodules.

Atherosclerosis (AS) is initiated by the activation of the endothelial cells, which is followed by a series of events that trigger the narrowing of blood vessels and the activation of inflammation. This study aimed to investigate in vitro the roles and underlying mechanisms of curdione in AS. Human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized low-density lipoprotein (ox-LDL) and then treated with curdione, after which the growth of the HUVECs and the related mechanisms were determined. HUVECs with ERBB4 overexpression were constructed to explore the role of ERBB4 in curdione-mediated AS. The interaction among ERBB4, methylation, and curdione was confirmed by chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) and dual luciferase reporter gene assays. Both curdione and ERBB4 overexpression individually and significantly enhanced viability and proliferation while suppressing apoptosis of the ox-LDL-induced HUVECs, and the combination of curdione and ERBB4 overexpression had better effects. Compared with the ox-LDL-induced HUVECs, both curdione and ERBB4 overexpression individually decreased the levels of IL-6, IL-1β, and IL-8 ( P < 0.05). They also upregulated Bax, caspase-3, E-cadherin, and F-actin while downregulating Bcl-2 and VEGF ( P < 0.05). Additionally, the ERBB4 bound to the DNMT1 gene, and the curdione participated in AS via the ERBB4 gene. The study demonstrated that either curdione or ERBB4 overexpression individually may ameliorate AS development by inhibiting apoptosis, inflammation, and the EndMT of HUVECs. In addition, curdione may protect the vascular endothelial cells and AS by regulating the DNMT1-mediated ERBB4 promoter methylation.

Introduction Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is associated with a 50% increase in subsequent risk for type 2 diabetes. There is increasing interest in identifying biomarkers that may facilitate the stratification of subsequent type 2 diabetes risk among women with GDM. In this study, we considered the choline acetyltransferase ( ChAT ) gene. CHAT plays a critical role in acetylcholine synthesis and regulates insulin secretion from the pancreatic islet to maintain glucose homeostasis. Methods We screened for deleterious variants in the ChAT gene in 12 GDM patients and 10 ethnically matched controls from a South African cohort. We isolated DNA from the placental samples of these patients and performed DNA sequencing of the protein-coding region of the ChAT gene. Sequence alignments and variant annotations were done using UGENE software and Ensembl VEP. Results A novel heterozygous missense variant in exon 8 of the ChAT gene was identified. The plausible phenotypic impact of the variant ChAT (NM_020549.5):c.1213C>G (p.Leu405Val) can be explained by haploinsufficiency, changing protein activities, strong transcription activity, and epigenetic repression activities of the variant. Also, structurally, the variant is located 18bp in-frame to a stop-gained variant (p.Gly411Ter). The RegulomeDB DNase expression data clearly show the identified variant in a peak expression in the spleen and placenta. This observation corroborates that the ChAT gene may play an essential role in GDM. Conclusion Taken together, the metric scores for this variant show that it could affect the functions of the gene, but more functional studies are necessary to validate these effects. Consequently, this study sets the stage for the future screening of a larger cohort and functional validation of deleterious variants to underpin the ChAT gene and GDM association.

Objective To establish a multi-level blood type identification system, comprehensively analyze the distribution characteristics and genetic polymorphisms of multi-system rare blood types in foreign blood donors, explore the application value of DNA sequencing technology in rare blood type screening, and evaluate its clinical significance in complex transfusion patients. Methods Blood samples from 277 foreign blood donors who participated in voluntary blood donation in Yiwu City were prospectively collected from June 2021 to March 2023. Serological typing of 24 antigens from 11 red blood cell blood group systems (ABO, Rh, Duffy, MNS, Kidd, Kell, Lutheran, P1PK, Lewis, H, and Diego) was performed using microcolumn agglutination and tube methods. First-generation sequencing technology was used to perform whole-exome sequencing of Duffy, Kell, Ss/GYPB, and Diego genes on screened rare phenotype samples to analyze genetic polymorphism characteristics. Key mutation sites were verified using multiplex PCR-sequencing. A rare blood type DNA database was established and compared with the international blood group gene database (BGMUT). Confirmed rare blood type units were preserved through programmed freezing, and their clinical application effects were tracked and analyzed. Results The 277 foreign blood donors were primarily from the Middle East and South Asia (71.8%), with major source countries including Syria (56 cases, 20.22%), Yemen (49 cases, 17.69%), Pakistan (24 cases, 8.66%), Iraq (20 cases, 7.22%), India (15 cases, 5.42%), Iran (14 cases, 5.05%), Mali (11 cases, 3.97%), and Jordan (10 cases, 3.61%). In blood type distribution, Fya antigen expression was highest among Indian (100%) and Pakistani (87.50%) donors; 63 cases of Fy(a−b−) were found, most commonly in donors from Mali and Yemen. S antigen expression was highest in donors from Syria (60.71%), India (60.00%), and Pakistan (58.33%); 47 cases of S+s− were detected. Additionally, 12 cases of Lua+ were found, distributed among Syria (3 cases), Iraq (2 cases), Yemen (2 cases), Jordan (2 cases), etc.; 5 cases of Kpa+ were from Yemen (2 cases), Pakistan, Iraq, and Jordan (1 case each). DNA sequencing revealed that GATA-1 promoter region mutation (c.-67T>C) in the Duffy gene was the primary molecular basis for the Fy(a−b−) phenotype, accounting for 96.8% (61/63). Multivariate analysis demonstrated significant clustering of blood group phenotypes by geographical regions ( p < 0.001), with the first two principal components explaining 78.3% of the variance in distribution patterns. Genotype–phenotype correlation analysis showed a concordance rate of 99.2% (248/250). During the study period, 41 rare phenotype blood units (74U) were screened and cryopreserved, including 14 units (24.5U) of Fy(a−b−), 25 units (45.5U) of Fy(a−b+), and 2 units (4.0U) of s(−). In clinical application, these units were successfully used in three difficult-to-match transfusion patients: a patient with multiple antibodies (anti-Fya, anti-Jka, and anti-C), a sickle cell disease patient requiring S-negative blood, and a pregnant woman with anti-Kpa antibodies. All cases showed satisfactory post-transfusion outcomes with no adverse reactions (24 h red cell recovery rates >90%). Conclusion Foreign blood donors exhibit significant regional and ethnic polymorphic characteristics in red cell blood types. A multi-level blood type identification system based on DNA sequencing can improve the accuracy and efficiency of rare blood type screening. Establishing a standardized genetic typing strategy for rare blood types in foreign donors has important clinical translation value for constructing diverse rare blood type resources and addressing complex transfusion needs.

Objective This study aimed to investigate the potential causal relationship between immune cell and the risk of ulcerative colitis (UC), and to explore whether serum metabolites may mediate this association, thereby suggesting potential biomarkers or therapeutic targets. Methods We conducted a Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies to evaluate both the direct effects and potential mediating roles of 731 immune cells and 1,400 serum metabolites in relation to UC. Instrumental variables were rigorously selected based on genome-wide significance and linkage disequilibrium thresholds. The primary analytical method was inverse variance weighted, supplemented by MR-Egger regression and weighted median methods to ensure robustness. Cochran’s Q test, MR-Egger intercept, and leave-one-out analysis were employed to evaluate heterogeneity and pleiotropy. Mediation MR analysis was conducted to examine potential metabolite-mediated pathways. Results We identified a statistically significant positive causal effect of CD39⁺ CD4⁺ T cell on UC risk (OR = 1.05, 95% CI = 1.03–1.08, beta_all = 0.05). Sensitivity analyses confirmed the robustness of this association, and reverse MR analysis indicated no causal effect of UC on CD39⁺ CD4⁺ T cell, suggesting a unidirectional relationship. Mediation analysis further revealed that succinyl carnitine (C4DC) partially mediated the effect of CD39⁺ CD4⁺ T cell on UC, with a mediation proportion of 3.3%. Conclusion Our findings suggest that CD39⁺ CD4⁺ T cell may increase the risk of UC, potentially by modulating the levels of succinyl carnitine (C4DC). These results indicate a potential immunometabolic pathway in UC pathogenesis and highlight CD39⁺ CD4⁺ T cell and C4DC as promising targets for further research. However, additional experimental validation is required to confirm these findings and assess their clinical relevance.

Background Postoperative cognitive dysfunction (POCD) is driven in part by microglial activation and the resulting neuroinflammatory response. Emerging evidence suggests that microRNAs regulate key inflammatory pathways in the central nervous system. In this study, we examined the role of the mmu‑miR‑125a/TRAF6 signaling axis in microglial activation under inflammatory conditions induced by lipopolysaccharide (LPS) and surgical trauma and evaluated whether dexmedetomidine (DEX) modulates this pathway to alleviate POCD. Methods Murine microglial cells were treated with LPS to induce activation. Expression levels of mmu‑miR‑125a and TRAF6 were quantified by qRT‑PCR and Western blotting. Bioinformatic prediction of miRNA binding sites was performed, and a luciferase reporter assay was used to confirm direct targeting of TRAF6 by mmu‑miR‑125a. Adult mice underwent standardized surgical trauma to induce POCD. Brain tissues were analyzed for microglial activation markers, cytokine levels, and expression of mmu‑miR‑125a and TRAF6. DEX was administered in both in vitro and in vivo models. The effects on cytokine release, microglial activation, and the mmu‑miR‑125a/TRAF6 axis were assessed. Results Our findings revealed significant alterations in the expression levels of TRAF6 and mmu-miR-125a during LPS-induced microglial activation. Through bioinformatics analysis and experimental validation, we identified TRAF6 as a direct target of mmu-miR-125a. The mmu-miR-125a/TRAF6 axis was found to be crucial for regulating microglial activation both in vitro , using an LPS-induced model, and in vivo, using a surgical trauma-induced POCD model. Moreover, we demonstrated that DEX, an alpha-2 adrenergic receptor agonist, effectively modulated the inflammatory cytokine release by targeting the mmu-miR-125a/TRAF6 axis in both models. The administration of DEX significantly suppressed microglial activation and TRAF6 expression, effects that were reversed by the inhibition of mmu-miR-125a. Conclusion Our study provides new insights into the molecular mechanisms underlying microglial activation and highlights the therapeutic potential of targeting the mmu-miR-125a/TRAF6 axis to alleviate neuroinflammation by the administration of DEX in POCD.

Background Heart failure remains a major public health issue, and there are still no reliable biomarkers for left ventricular ejection fraction (LVEF). Objective To screen for differential metabolites in the blood of HFpEF, HFmrEF, and HFrEF patients based on metabolomics analysis of their blood samples. Methods Total 44 patients in HFpEF group, 30 patients in HFmrEF group, and 36 patients in HFrEF group were selected. The blood metabolites were analyzed by liquid chromatography high-resolution mass spectrometry and classified by principal component analysis, and then potential biomarker were screened. Partial least squares discriminant analysis was used to model and investigate the predictive ability of biomarkers for LVEF. Results Blood metabolite profiles of HFpEF, HFmrEF, and HFrEF groups could be well distinguished, and seven potential biomarkers were identified, such as phosphatidylcholine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylcholine, ceramide, sphingosine, and sphingomyelin. Four metabolic pathways, such as glycerol phospholipid metabolic pathway, linoleic acid metabolic pathway, purine pyrimidine metabolism pathway, and linolenic acid metabolism pathway were identified, among which glycerol phospholipid metabolism pathway was the most significant. Conclusion The changes in glycerol phospholipid metabolism pathway may help identify HFpEF, HFmrEF, and HFrEF.

Objectives Accurate diagnosis of acute cholecystitis (AC) is critical because early laparoscopic cholecystectomy significantly reduces complications and mortality. This study evaluates the predictive value of inflammatory indices and hematological markers in diagnosing AC. Methods A retrospective review was performed on early laparoscopic cholecystectomy cases at the Gaziosmanpaşa Training and Research Hospital in Istanbul between August 2013 and August 2023. Patient demographics, preoperative laboratory values, inflammatory indices – including neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) – were evaluated, along with hospital length of stay and histopathological outcomes. Results Among 249 patients, 34 (13.6%) were diagnosed with AC, comprising 76 males (30.5%) and 173 females (69.5%), with a mean age of 48.9 ± 14.6 years. The median hospital length of stay was 3 days (range: 1–21). Significant elevations in both the SIRI and neutrophil count were observed in AC cases compared to controls ( P < 0.001). ROC (receiver operating characteristic) curve analysis demonstrated comparable diagnostic performance for the SIRI (AUC = 0.746; 95% CI: 0.658–0.835; optimal cutoff: 1.98) and neutrophil count (AUC = 0.746; 95% CI: 0.658–0.835; optimal cutoff: 7.1 × 10 3 /μL) in predicting AC. Conclusions The SIRI and neutrophil count are reliable markers that can improve the diagnostic accuracy and guide early management of AC.

Background Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic fat accumulation and is closely associated with obesity, diabetes, and hyperlipidemia. Objectives This study explores the effects of pachymaran on NAFLD induced by a high-fat diet (HFD) in a murine model. Methods Thirty male C57BL/6 mice were allocated into five groups: normal diet (ND), NAFLD, and high-, medium-, and low-dose pachymaran (200, 100, and 50 mg/kg, respectively). All groups except the ND were fed a HFD to induce NAFLD. The pachymaran groups received daily intragastric pachymaran for eight weeks. Post-treatment, liver weight were recorded, serum indices assessed, and hepatic pathology evaluated via histological and Oil Red O staining. Adenylate-activated protein kinase (AMPK) gene expression was analyzed through western blotting. Results The body weight and liver gain (87.8 and 23.0%) in the high-dose pachymaran group were significantly less than those (154.2 and 82.0%) in the NAFLD group ( P < 0.05). Fat content and serum indices improvements correlated with increased pachymaran doses. Histological analyses indicated significant alleviation of hepatocyte hypertrophy and ballooning steatosis in treated groups. Oil Red O staining confirmed a substantial decrease in hepatic lipid droplets, and western blot results indicated a significant increase in AMPK phosphorylation following treatment ( P < 0.05). Conclusions Pachymaran effectively mitigated fat accumulation, hepatocyte degeneration, and injury in mice with diet-induced NAFLD, likely through modulation of the AMPK pathway.

Study objective The main objective of this study was to investigate the association between CD4+ and CD8+ lymphocyte values and disease severity, need for oxygen therapy and disease outcomes. Design The research was designed as a cross-sectional observational study. Setting This study was conducted at the Clinic for Infectious Diseases, University Clinical Center Kragujevac, as a COVID-19 treatment center. Participants The study group consisted of a total of 101 adult hospitalized patients with confirmed COVID-19 infection, excluding patients under 18 years of age, patients with malignant diseases, tuberculosis, hepatitis, immune disorders, pregnant women, or HIV-positive patients. SARS-CoV2 infection was diagnosed by rapid antigen tests or real-time reverse transcription polymerase chain reaction from a nasal swab. Interventions The patients were classified into two groups based on oxygen therapy needs, disease severity, and disease outcomes. Results and conclusions Low CD4+ and CD8+ T cell values were associated with severe clinical presentation, more need for oxygen therapy as well as poor disease outcome. Receiver operating characteristic analysis provided cutoff values to support predicting the aforementioned variables, establishing CD4+ and CD8+ values as significant prognostic biomarkers. Future studies should be aimed at identifying factors that lead to gender differences in the immune response.

We aimed to explore the regulatory effects of methyltransferase-like 3 (METTL3) on diabetic retinopathy (DR) by regulating the m6A modification of SOX2 mRNA and elucidating the underlying molecular mechanism. The DR model was established by stimulating human retinal endothelial cells (HRECs) with high glucose (HG). METTL3, insulin-like growth factor 2 binding protein 2 (IGF2BP2), and SOX2 levels in the sera of patients with DR and HRECs were determined using qRT-PCR and western blotting. Moreover, the interactions between SOX2 and METTL3 or IGF2BP2 were confirmed using RNA-binding protein immunoprecipitation (RIP) experiments. Furthermore, HRECs proliferation and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry, respectively. The protein level of cleaved-caspase3 and caspase3 in HRECs were evaluated using western blotting. The results indicated that the expression of METTL3, IGF2BP2, and SOX2 was notably decreased in the serum of patients with DR, as well as in HRECs under HGs. RIP further verified the relationship between METTL3 and SOX2 mRNA expression. HG treatment inhibited HREC viability, increased apoptosis, and enhanced cleaved-caspase3 expression and cleaved-caspase3/caspase3 ratio. Upregulation of METTL3 significantly restored the effects of HG, whereas SOX2 knockdown partially reversed the regulatory effects of METTL3 on HRECs. In summary, METTL3 blocks the progression of DR by regulating m6A modification on SOX2 mRNA.

Aim To discover the predictive indicators of the risk of interstitial lung disease (ILD) after treatment of malignant tumors from myositis-specific autoantibodies (MSA) and myositis-associated autoantibodies (MAA) and explore possible predictive value and significance. Methods A total of 73 patients hospitalized in the Shulan (Hangzhou) Hospital from January 2020 to March 2021 were screened retrospectively, they all completed the MSA and MAA, and the imaging was consistent with changes in ILD. We analyzed the characteristics of MSA and MAA in tumor patients and non-tumor patients, and the characteristics of MSA and MAA positive in patients with ILD after treatment. Results A total of 58 patients with ILD were diagnosed, 19 patients (32.76%) with malignant tumors, 16 patients with positive MSA or MAA (84.21%), of which 10 (50%) patients had anti-RO-52 antibodies. After treatment, 12 cases (46.15%) developed ILD and 10 cases (90.91%) had a positive spectrum of specific inflammatory diseases. Conclusion The MSA and MAA may have a predictive effect on people who are prone to ILD during the treatment of malignant tumors, and the anti-RO-52 antibody may be an important predictive antibody index. Graphical abstract

Disruption of cerebrospinal fluid (CSF) metabolites affects brain function and cognition, potentially altering the brain structure. To elucidate the causal relationships between CSF metabolites and the neurological outcomes, we conducted a two-sample Mendelian randomization analysis. Genome-wide association data from 689 individuals of European descent provided exposure levels for metabolites, analyzed alongside gene associations for cognitive performance ( N  =  257,841), brain atrophy measures (cortical surface area and thickness; N  =  51,665), and hippocampal volume ( N  =  33,536). Our analysis identified 30 metabolites exhibiting causal associations with brain atrophy and cognitive function: 20 linked to cognition and 10 to structural atrophy. Notably, butyrate correlated strongest with the cortical surface area, bilirubin with the cortical thickness, methionine sulfoxide with the hippocampal volume, threonate with cognitive performance, while oxidized Cys-gly, N 6-succinyladenosine, and N -acetylglucosamine were linked to fluid intelligence, prospective memory, and reaction time, respectively. Pathway analyses revealed that butanoate and niacinamide/niacin ester metabolism are significantly associated with brain atrophy and cognitive performance. These findings position CSF metabolites as promising therapeutic targets for neurodegenerative diseases, providing a causal framework to prioritize interventions. Experimental studies building on this genetic evidence hold potential to accelerate the development of mechanism-driven therapies targeting metabolic pathways in neurodegeneration.

Background Sarcoidosis is characterized by the proliferation of noncaseating granulomas and presents as a complex chronic inflammatory disease. Autophagy plays a crucial role in the initiation, progression, and treatment resistance of various cancers. Despite the recognized importance of autophagy, the involvement of autophagy-related genes (ARGs) in the pathophysiology of ocular sarcoidosis (OS) remains largely unexplored. Methods We intersected differentially expressed genes with a curated list of 177 ARGs to identify candidates potentially involved in OS. Advanced methodologies, including GSEA and GSVA, were employed to explore the biological functions. Further refinement using Lasso regression and SVM-RFE allowed for the identification of key hub genes and the assessment of their diagnostic potential for OS. Results Our investigation identified 11 ARGs (DRAM1, SOGA1, ATG16L2, FYCO1, ATG7, ATG12, ATG14, KIAA0226, KIAA1324, KIAA1324L, and KIAA0226L) closely associated with OS. Functional analyses revealed their involvement in processes such as extracellular stimulus, response to nutrient levels, and positive regulation of catabolic process. Importantly, the diagnostic capabilities of these ARGs demonstrated significant efficacy in distinguishing OS from unaffected states. Conclusions Through rigorous bioinformatics analyses, this study identifies 11 ARGs as novel biomarker candidates for OS, elucidating their potential roles in the disease’s pathogenesis.

Background Behçet’s disease, first described by Hippocrates and later recognized in modern medicine after Hulusi Behçet’s description in 1937, is a complex vasculitis often referred to as the “Silk Road” disease. It is more prevalent in the Middle East and Mediterranean regions, primarily affecting males aged 25–35. Case presentation This study first describes the clinical presentation, timeline, diagnostic evaluation, and therapeutic interventions of one patient. Subsequently, the challenges in diagnosing the disease and selecting treatment strategies are discussed in detail. Finally, the clinical outcomes and treatment effects during the follow-up period are reported. Conclusion This case underscores the necessity of comprehensive diagnosis and integrated treatment for diseases with complex multisystem symptoms. Multidisciplinary collaboration plays a crucial role in the management of such conditions.

Background Uterine fibroids (UF) affect up to 70–80% of women by age 50 and are associated with heavy menstrual bleedings, pelvic discomfort, and reduced quality of life. Uterine artery embolization (UAE) is a minimally invasive procedure that aims to reduce fibroid-related symptoms and improve patients’ quality of life. Materials and methods A prospective single-center study was conducted on 40 women who underwent UAE between November 2018 and June 2023. Primary outcomes were evaluated using the Uterine Fibroid Symptom and Quality-of-Life (UFS-QoL) questionnaire to assess symptom severity and health-related quality-of-life scores. Secondary outcomes include pain intensity, complications, requirement of additional treatments, and duration of symptoms after discharge. Results Thirty-three patients completed the follow-up UFS-QoL questionnaire. The mean age and the mean follow-up time were 47 years (SD 14 years) and 10 months (SD 4 months), respectively. Substantial improvements were observed within all domains of the UFS-QoL questionnaire ( p < 0.001), particularly in symptom severity, where 94% of patients experienced a benefit. All Health Related Quality-of-Life (HRQL) domains statistically significantly improved (73–91%; p < 0.001). 67% of patients did not require further treatments. Pelvic pain, according to VAS, improved by 2.1 (0 = much better; 5 = no change; 10 = worse). Post-procedural complications were minor, 70% of patients reported symptoms persisted up to 5 days after discharge, and 88% resolved within 2 weeks. Despite a 45.5% rate of minor complications, including pain and transitory bleeding, 88% of patients would recommend UAE, underlining its safety and effectiveness. Discussion and conclusion UAE offers substantial benefits for symptomatic fibroids, significantly improving HRQoL, symptom severity and pelvic pain scores, making it a valuable alternative to surgery. Complications were minor and short-lived, and the majority of patients were satisfied with the results, with no need for additional treatments. Further research is warranted to generate peri-procedural pain management consensus guidelines, clinical outcomes of radial access, and fertility-related outcomes.

This study aimed to identify candidate diagnostic biomarkers for steroid-induced osteonecrosis of the femoral head (SONFH). Two datasets were downloaded from the Gene Expression Omnibus for analyses of differentially expressed genes (DEGs) and lipid scores in SONFH and control groups and a weighted gene co-expression network analysis. Overlap between genes in the disease-related module, DEGs, and lipid metabolism-related genes was evaluated to obtain lipid metabolism-related DEGs. A diagnostic model was constructed and evaluated using a nomogram analysis and calibration curves. Correlations between immune cells and lipid metabolism-related DEGs in the model were evaluated. In total, 1,724 DEGs were screened between the SONFH and control groups. Seven SONFH-related modules and 18 lipid metabolism-related DEGs were identified. A total of six optimized genes, CDK8 , CHPT1 , DPEP3 , ORMDL3 , PIP5K1B , and PPT2 , were obtained. A model based on these genes had good diagnostic performance for SONFH in GSE123568 and GSE74089. The six genes were significantly related to two immune cell subsets, myeloid dendritic cell activated and neutrophil. These six genes may be novel biomarkers for SONFH and the combination is a potential diagnostic signature.

Background The exosomal microRNAs (exomiRNAs) are promising novel biomarkers for clinical detection and prognosis assessment of human cancers. The aim of this study was to identify potential exomiRNAs as biomarkers in ovarian cancer (OC). Methods The candidate exomiRNAs were screened by analysis of GSE235525, GSE239685, and GSE216150 datasets and further validated in exosome samples from the serum of 61 patients with OC and OC cell lines by qPCR. The correlations between exomiRNAs expression and clinicopathological features of OC patients were assessed, and Kaplan–Meier survival and receiver operating characteristic curves were employed to analyze the prognostic and diagnostic values. Results We found that exomiR-188-3p expression was downregulated in patients with OC and OC cell lines compared with healthy controls and normal cells. Decreased exomiR-188-3p was associated with advanced FIGO stage, lymph node metastasis, and distant metastasis. The area under the curve (AUC) values of exomiR-188-3p for differentiating OC, stage IA–IIA OC, and no metastatic OC from healthy controls were 0.8983, 0.8461, and 0.8179. And combination of exomiR-188-3p and CA125 yields better diagnostic efficacy, with AUC values of 0.9323, 0.8925, and 0.9120. Lower expression of exomiR-188-3p predicted a poor overall survival and progression-free survival in patients with OC. Conclusion Decreased exomiR-188-3p could be a potential early diagnostic and prognostic biomarker for OC patients.

Objective This study examines the efficacy of ultrasound (US)-guided paravertebral nerve block (PVB) with and without MRI fusion for chronic back pain management. Methods A retrospective analysis of 20 patients, split into US–MRI fusion-guided (IF group, n = 10) and traditional US-guided (U group, n = 10) PVB, was conducted. Pain intensity, gabapentin dosage, procedure duration, and treatment efficacy were compared using numerical rating scale (NRS) scores. Results An hour after receiving treatment, the IF group showed a marked reduction in NRS scores (2.2 ± 0.9), significantly lower than those observed in the U group (2.5 ± 1.0; p < 0.05). Nonetheless, the difference in average NRS scores between the groups was not statistically significant 7 days post-treatment (IF group, 3.5 ± 0.8; U group, 3.4 ± 1.3; p > 0.05). The U group reported four instances of transient dizziness and diminished limb muscle strength, lasting between 30 and 90 min, which naturally resolved without intervention. No significant adverse effects were noted in the IF group. Conclusions Integrating US with MRI for PVB guidance emerges as a groundbreaking and efficacious strategy in chronic back pain treatment, showcasing significant improvements in safety and initial pain alleviation compared to the conventional use of US guidance alone.

Objective Peptide-encoding roles of lncRNAs are emerging in cancer biology. This study explores the function of the CCAT1-70aa peptide in hepatocellular carcinoma (HCC) and its underlying mechanisms. Methods Immunohistochemistry was used to detect CCAT1-70aa expression in HCC and adjacent tissues. An expression vector verified CCAT1’s role in encoding CCAT1-70aa. Cell counting kit-8 and Transwell assays assessed the effects of CCAT1-70aa on HCC cell proliferation and invasion. Small-interfering RNAs (siRNAs) targeting CCAT1 were transfected into HCC cells to examine CCAT1-70aa expression. The role of the MAPK/ERK pathway was confirmed via Western blot and the ERK inhibitor FR180204. Results CCAT1-70aa was significantly upregulated in HCC tissues, correlating with tumor stage, serum alpha-fetoprotein levels, and vascular invasion. siRNA-mediated CCAT1 silencing reduced CCAT1-70aa expression, supporting that CCAT1-70aa is translated from lncRNA CCAT1. CCAT1-70aa, a 70-amino acid peptide, enhanced proliferation and invasion, activating the MAPK/ERK pathway, with its effects mitigated by ERK inhibition. Conclusion The CCAT1-70aa peptide is overexpressed in HCC and linked to aggressive tumor characteristics. It promotes proliferation and invasion via the MAPK/ERK pathway, providing insights for HCC diagnosis and treatment strategies.

Objective This study aims to investigate the potential of electroacupuncture to mitigate myocardial ischemia–reperfusion injury (MIRI) by influencing N6-methyladenosine (m6A) methylation through modulation of the fat mass and obesity-associated protein (FTO). Methods An experimental murine model of MIRI was established by surgically occluding the left anterior descending coronary artery, followed by reperfusion. Electroacupuncture treatment targeting Neiguan acupoints was administered 7 days before ischemia induction. Cardiac function was evaluated using echocardiography, and myocardial infarction size was assessed through Evans Blue and triphenyltetrazolium chloride dual staining. To measure m6A methylation and mRNA expression of FTO and mediator complex subunit 1 (Med1), RNA immunoprecipitation and quantitative polymerase chain reaction were utilized. Western blot analysis was conducted to determine the protein expression levels of Med1, Bcl-2, and Bax. Results Electroacupuncture pretreatment was associated with a reduction in myocardial injury, demonstrated by preserved ejection fraction and reduced infarct size. Enhanced FTO expression and decreased m6A methylation were observed in myocardial tissue following electroacupuncture treatment. Additionally, Med1 – a downstream target of m6A – exhibited decreased mRNA expression in the electroacupuncture-treated group, correlating with reduced cardiomyocyte apoptosis. Conclusion Electroacupuncture pretreatment may confer cardioprotective effects in MIRI by upregulating FTO, thereby modulating m6A methylation and reducing Med1 expression.

Background Emerging evidence suggests that hemorrhoids are associated with cardiovascular disease (CVD). However, the causal associations between hemorrhoids and CVD remain elusive. This study aimed to investigate potential causal links between hemorrhoids and various heart conditions, including arrhythmia, heart failure, myocardial infarction, atrial fibrillation, and coronary artery disease. Methods A two-sample bidirectional Mendelian randomization (MR) analysis was conducted using summary statistics of hemorrhoids and CVD from publicly available genome-wide association studies (GWAS). The MR analyses utilized inverse-variance weighted, weighted median, weighted mode, and MR-Egger methods. Sensitivity analyses included Cochran’s Q test, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis. A radial MR analysis was performed after excluding outliers. Results Genetically determined hemorrhoids did not exhibit a causal effect on arrhythmia (OR = 0.9998, P = 0.83), heart failure (OR = 0.94, P = 0.14), myocardial infarction (OR = 0.94, P = 0.27), atrial fibrillation (OR = 0.98, P = 0.55), or coronary artery disease (OR = 0.99, P = 0.84). The reverse analysis yielded similar results. Consistent results were observed with alternative MR methods, and the absence of significant heterogeneity was confirmed. The radial MR analyses support the conclusions in the forward and reverse analyses. Conclusions This bidirectional MR analysis did not find statistical causal association between hemorrhoids and CVD, suggesting the possibility of shared risk factors such as obesity and diet. Further prevention strategies for CVD could focus on the management of common risk factors.

Objective Hypertrophic scars (HS) are a fibrotic proliferative disorder that results from an abnormal wound healing process, presenting significant challenges for clinical intervention. The primary characteristics of HS include excessive collagen deposition and angiogenesis. In recent years, the study of mesenchymal stem cells (MSCs) and their derived exosomes has emerged as a prominent area of research within the academic community. However, the therapeutic application of MSCs is impeded by several challenges, including immune rejection, sourcing limitations, ethical dilemmas, and difficulties related to the scalability of exosome production. Cell-free adipose extract (CEFAE), a novel bioproduct derived from adipose tissue, is rich in various active protein factors that are essential for MSCs and their exosomes. CEFAE presents several advantages, including low immunogenicity, non-tumorigenicity, and a high degree of clinical safety. However, the application of CEFAE in the prevention and treatment of scar formation has not been adequately validated through experimental studies. Methods This research established a rabbit ear scar model, establishing a control group, a low-concentration CEFAE group (L-CEFAE), and a high-concentration CEFAE group (H-CEFAE) to evaluate wound treatment. Observations of scar changes were conducted at 14 and 28 days post-treatment, supplemented by histological and immunohistochemical analyses. Results Histological analysis revealed that the H-CEFAE group achieved optimal outcomes, with the lowest collagen deposition, thinnest epidermal/dermal thickness, and the most orderly collagen alignment. Furthermore, the formation of new blood vessels in the H-CEFAE group showed a significant reduction over time, resulting in decreased blood supply, which is beneficial for suppressing scar tissue development. Quantification of COL I, COL III, and vascular endothelial growth factor also supports these results. Conclusion The findings indicated that high-concentration CEFAE has a beneficial preventive and therapeutic effect on scar proliferation. Furthermore, the study explored the potential mechanisms by which CEFAE inhibits scar proliferation, thereby providing novel therapeutic strategies for the prevention and management of clinical scars.

Objectives Demodex mite infestation is one of the most prevalent causes of blepharitis. This study was designed to evaluate whether Demodex blepharitis was related to novel inflammatory markers. Methods 89 patients with Demodex blepharitis and 76 age-matched participants without blepharitis enrolled in the study. Test parameters such as hemoglobin, albumin, neutrophil, lymphocyte, monocyte, platelet, WBC, CRP, HALP score, systemic immune-inflammation-index (SII), pan-immune-inflammation value (PIV), and Demodex density were evaluated. Results CRP values were numerically higher, and albumin levels were lower in the patient group, even though the differences between these levels in both groups were not statistically significant ( p > 0.05). SII and PIV indices were shown to be numerically higher, and HALP score levels were statistically significantly lower in the patient group ( p = 0.134, p = 0.319, p = 0.001). The ROC analysis was carried out, and the optimal cutoff point for the HALP score was designated using the formula of Youden’s index. It was suggested that values below 504.8 for the HALP score can be used in the diagnosis of Demodex blepharitis with 66.5% of sensitivity and 78% of specificity. Conclusions CRP, SII, PIV, and specifically HALP scores, which are easy to obtain and easy to use in evaluating inflammation, may also be useful in assessing inflammation in Demodex blepharitis. Particularly, HALP scores may give clinicians the information about poor immune conditions and chronic inflammation in the patients.

Background Recent studies have highlighted that one of the main drivers for metastatic formation and resistance to the therapy are circulating tumor cells (CTCs) and cancer stem-like cells (CSCs). Measuring the CTCs has emerged as a non-invasive procedure for selecting the patients with higher risk of progression/relapse. However, still there are no methods enabling the identification of stem-like phenotype of the CTCs. Methods The image-based method was used for the identification of the circulating cancer stem-like cells (CCSCs) in metastatic breast cancer patients. The method was optimized using the CSCs established in the mammosphere culture of MCF-7 cells. Next the protocol was implemented to identify the CCSCs in samples collected from 60 patients. Results The recovery ratio for CCSCs identification using the established method was ∼60%. The CCSCs were identified as rare events accruing only in 2 patients out of 60, who participated in the study. Interestingly, the CCSCs were found only in CTC clusters. The analysis of SOX2 expression in formalin-fixed, paraffin-embedded material, revealed that the SOX2 expression was present in primary tumor samples. Conclusion The CCSCs presence was found to be a very rare event. The obtained results suggest that the CCSCs are mainly present in CTC clusters and stem-like reprograming of the cancer cells might occur early, in the primary tumor.

Purpose The purpose of this study was to evaluate the risk and prognostic factors of stage IVB cervical cancer with brain metastasis from a population-based database, the Surveillance, Epidemiology and End Results (SEER). Patients and methods Cervical cancer patients initially diagnosed with brain metastasis between 2010 and 2019 were included in this study. The risk factors of developing brain metastasis were evaluated by logistic regression model with corresponding 95% confidence interval (95% CI). Survival analysis was performed through the Kaplan–Meier method, log-rank test, and Cox proportional hazards model. Results A total of 88 (88/25,476, 0.35%) cervical cancer patients initially diagnosed with brain metastasis between 2010 and 2019 were retrieved. Accompanied with lung, bone, or liver metastasis (all P < 0.001) was shown to be independent risk factors for developing brain metastasis. Patients with brain metastasis indicated a poor prognosis ( P < 0.001, hazards ratio [HR] = 2.84, 95% CI = 1.71–4.72) with a 2.84-fold elevated risk of death compared with patients without brain metastasis. The median survival month for patients with brain metastasis was 6 months, which is much shorter compared with the lung (9 months) or liver (8.5 months) or bone (11 months) metastasis group. Along with lower tumor grade ( P = 0.001, HR = 0.27, 95% CI = 0.09–0.76) and with bone metastasis ( P = 0.007, HR = 2.74, 95% CI = 1.33–5.67) demonstrated poor overall survival outcomes in patients with brain metastasis, with a 3.7- and 1.33-fold higher risk of death, respectively. In terms of treatment modality, chemoradiotherapy tended to prolong the survival of stage IVB cervical cancer patients with brain metastasis ( P = 0.001, HR = 0.17, 95% CI = 0.06–0.48), with an 83% reduction in the risk of death. Conclusion In conclusion, the prognosis of stage IVB cervical cancer patients with brain metastasis remains poor. Chemoradiotherapy may provide survival benefits, which deserves large-scale prospective clinical trials to confirm.

Background For pediatric patients, there is still controversy regarding the anastomotic technique used for gastrointestinal construction. The study was to evaluate the continuous single-layer (CSL) intestinal anastomosis method compared with the two-layered interrupted anastomosis. Methods We retrospectively reviewed the medical records of the eligible patients following CSL anastomosis ( n = 252) and interrupted double-layer (IDL) anastomosis ( n = 196). The influences of CSL or IDL anastomosis on perioperative outcomes, including postoperative complications, anastomotic leakage, hospitalization cost, and postoperative hospital stay, were evaluated. Results No significant differences were found between the CSL and IDL groups in terms of anastomotic leakage or postoperative complications. CSL anastomosis was related to favorable clinical outcomes, including anastomotic time (11.6 ± 3.8 vs 24.3 ± 5.9 min, p < 0.001) and operative time (111.6 ± 48.6 vs 124.1 ± 54.2 min, p = 0.041). There was a decrease in inflammation variable (e.g., C-reactive protein) on postoperative day 5 (10.6 ± 5.8 vs 12.8 ± 6.6 mg/L, p = 0.032) in patients with CSL anastomoses compared to the IDL group. Conclusions The beneficial effects of CSL anastomosis in pediatric patients were demonstrated with respect to anastomotic time, length of postoperative recovery, and cost incurred.

Background Intraperitoneal (IP) chemotherapy (IPC), including hyperthermic intraperitoneal chemotherapy (HIPEC), has emerged as a promising approach to control peritoneal metastases in gastrointestinal (GI) cancers. However, the safety profile and toxicity spectrum of IPC remain incompletely understood. This study aimed to evaluate the incidence of hematologic and biochemical adverse reactions following surgery with or without IPC and to compare the toxicity profiles of normothermic IPC and HIPEC. Additionally, potential risk factors for liver injury were investigated to guide clinical management. Methods In this retrospective cohort study, 449 patients with gastric or colorectal cancer undergoing surgical resection between January 2015 and September 2019 were analyzed. Patients were categorized into three groups: surgery alone ( n = 171), surgery + normothermic IPC (IPC group, n = 82), and surgery + HIPEC (HIPEC group, n = 196). Baseline demographic and clinicopathological data, IPC details (including drug regimen, HIPEC technique [open vs closed], and perfusion duration), and postoperative laboratory toxicities were recorded. Hematologic toxicities (leucopenia, neutropenia, thrombocytopenia, and hemoglobin decline) and biochemical toxicities (liver and renal function abnormalities and D-dimer elevation) were graded according to CTCAE v5.0. Group comparisons were performed using χ 2 or ANOVA tests. Due to a higher proportion of advanced-stage patients in the HIPEC group, stratified analyses were performed by clinical stage (I–II vs III–IV). Logistic regression was used to identify independent risk factors for liver injury in both IPC and HIPEC groups. Results Baseline characteristics were comparable across groups except for clinical stage, with the HIPEC group having a higher percentage of advanced-stage patients (79.6 vs 59.8%, P <0.05). Compared with the surgery-alone group, both IPC and HIPEC groups had significantly higher incidences of hemoglobin decline (25.7% vs 39.0% vs 49.0%, respectively; P <0.01), liver injury (37.4% vs 62.2% vs 60.7%, P <0.01), and D-dimer elevation (47.4% vs 68.3% vs 72.9%, P <0.01). In contrast, the incidences of leucopenia, neutropenia, and renal impairment were low (<12%) and did not differ significantly among groups. Thrombocytopenia was significantly more frequent in the HIPEC group than in the surgery-alone group (7.7 vs 2.9%, P = 0.046). Stratified analyses revealed no significant differences in adverse reaction rates between the IPC and HIPEC groups when adjusted by clinical stage. Multivariate logistic regression indicated that, in the IPC group, severe postoperative GI reactions ( ≥Grade II; OR, 3.72; 95% CI, 1.20–11.55; P = 0.023) and the use of a platinum plus docetaxel regimen (OR, 8.75; 95% CI, 1.78–43.12; P = 0.008) were independent predictors of liver injury. In the HIPEC group, the platinum plus docetaxel regimen was also associated with higher liver toxicity, and the open HIPEC technique significantly increased the risk (OR 4.80, 95% CI 1.26–18.38, P = 0.020). Conclusions Both normothermic IPC and HIPEC significantly increase the risk of certain perioperative laboratory abnormalities – specifically, anemia, liver injury, and a hypercoagulable state – compared to surgery alone. Notably, the addition of hyperthermia does not appear to significantly exacerbate the overall toxicity when clinical stage is considered. The chemotherapeutic regimen and HIPEC technique (open vs closed) are key determinants of liver injury. These findings underscore the importance of tailoring IPC protocols and implementing targeted supportive measures, such as liver protection and thromboprophylaxis, to optimize treatment safety in GI cancer patients.

Objective Endotoxin tolerance (ET) has been demonstrated to attenuate the inflammatory response in murine models of sepsis. This study seeks to elucidate the underlying mechanisms by which ET modulates inflammation in sepsis, with a particular focus on macrophage autophagy. Methods An in vivo sepsis model was generated using cecal ligation and perforation, while an in vitro model of inflammatory injury was induced via lipopolysaccharide (LPS) administration. ET was established through pretreatment with low-dose LPS. Subsequent analyses were conducted to assess the presence of the NLRP3 inflammasome, autophagic flux, and the expression levels of TRIM26. Results Heightened inflammation was observed in the TNF-α levels and various organs of the sepsis group; conversely, inflammation was reduced in the group receiving ET treatment. Upon stimulation with LPS, primary mouse peritoneal macrophages exhibited activation of the NLRP3 inflammasome and autophagy, accumulation of mitochondrial reactive oxygen species, compromised membrane potential, resulting in cell apoptosis, and decreased expression of TRIM26. ET was found to enhance autophagy, suppress the activation of NLRP3 inflammasomes, and upregulate the expression of TRIM26. Interestingly, modulation of autophagy levels either reversed or intensified the protective effects of ET on macrophages in vitro . Knockdown of TRIM26 using small interfering RNA (siRNA) resulted in increased NLRP3 inflammasome activation and accumulation of P62. Conclusion We reveal that ET restores the autophagic flux in macrophages, inhibit NLRP3 inflammasome activation, and mitigate inflammatory damage in septic mice, potentially through the regulation of TRIM26.

Background Laparoscopic adrenalectomy (LA) is the gold standard technique for well-selected patients with an adrenal mass. The surgical team’s experience is an essential factor in the surgical outcome. Objective The aim of this study was to assess the outcomes of patients who underwent lateral transperitoneal LA to remove their adrenal mass. Methods In this case-series study, 20 consecutive patients with adrenal mass were enrolled in Sulaimani Teaching Hospital, Sulaimaniyah, Iraq, from March 2019 to March 2022. Patients underwent lateral transperitoneal LA under general anaesthesia. Then, the type of LA, operation time, mass size, hospital stay, histopathological finding, and postoperative complications were assessed. Results Most patients were females (65%), underwent left-sided LA (55%), had a nonfunctioning mass (55%), and had no postoperative complications (85%). The mean operation time was 95 ± 2.0 min, and the mean hospital stay was 3.2 ± 1.5 days. Most patients were detected incidentally through radiology (55%), while others were detected after biochemical tests were done, including cases of pheochromocytoma (25%), hypercortisolism (10%), and hyperaldosteronism (10%). Most patients had benign cortical adenoma (45%), followed by benign medullary pheochromocytoma (25%), myelolipoma (15%), oncocytoma, adrenal hyperplasia, and ganglioneuroma (5.0% each). Conclusions LA seems to be a safe and feasible option for selected cases in this locality.

Background Diabetic retinopathy (DR), as a frequent complication of diabetes mellitus, is a common cause of vision impairment and blindness. Microglial activation plays an important role in the pathological cascade of DR, and novel potential therapeutics is needed to interfere with this process. Petunidin (PET) is one of the most abundant natural anthocyanins with the biological activities of anti-inflammation, anti-cancer, and anti-microbial. Objective The purpose of this study is to investigate the effect of PET against lipopolysaccharide (LPS)-induced retinal microglia inflammatory response as well as the underpinning mechanism. Methods Cell viability was determined using MTT assay. Cytokines secretion was determined using ELISA assay. iTRAQ-based proteomic analysis was used for the identification of differentially expressed proteins. Western blot analysis, Co-IP and immunofluorescence analysis were applied in the study. Results The results showed that PET pre-treatment significantly reduced LPS-induced cytokines secretion in BV2 cells and primary retinal microglia, as well as lipocalin 2 (LCN2) upregulation in BV2 cells by suppressing activation of O -GlcNAc modification and activation of NF‑κB. Further study revealed that PET inactivated NF‑κB by down-regulating OGT in BV2 cells, indicating that the protective effect of PET against LPS-induced retinal microglia inflammatory response was achieved by regulating OGT/NF-κB/LCN2 axis. Conclusion Our findings may contribute to the potential clinical use of PET in treating DR and suggest OGT/NF-κB/LCN2 axis may be the potential therapeutic target of this disease.

Background Acute cholecystitis (AC) is a common condition in emergency departments (EDs), where timely diagnosis and severity assessment are critical for treatment decisions and outcome prediction. Methods This study included 194 patients with AC to evaluate the diagnostic and severity-grading performance of procalcitonin (PCT) and C-reactive protein (CRP). Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for discriminating between severity grades according to the Tokyo Guidelines. Results Elevated levels of PCT and CRP were observed in 73.2 and 67% of cases, respectively. PCT demonstrated a sensitivity of 75.6% and specificity of 64.8% at a cut-off value of ≤ 0.595 ng/mL for distinguishing grade I from grades II to III. For differentiating grade III from grades I to II, PCT showed a sensitivity of 62.5% and specificity of 92.1% at a cut-off value of ≥5.095 ng/mL. Similarly, CRP had a sensitivity of 82.9% and specificity of 64.8% at a cut-off value of ≤78 mg/L for grade I versus grades II to III, and a sensitivity of 62.5% and specificity of 69.7% at a cut-off value of ≥82.5 mg/L for grade III versus grades I to II. Conclusion Both PCT and CRP are valuable biomarkers for diagnosing AC and assessing its severity.

Background and aim The aim of this study is to investigate whether certain clinical nomograms influencing the success of extracorporeal shock wave lithotripsy (ESWL) also play a role in determining the number of treatment sessions required in patients who achieved stone-free status following ESWL. Methods The data of 354 patients with successful ESWL outcomes were analyzed. Patients were evaluated 4–6 weeks post-ESWL using X-ray, ultrasound, or computed tomography. The presence of residual stones larger than 4 mm was considered a treatment failure. Data recorded included age, gender, laterality of stone localization (right/left), stone location (renal pelvis, mid calyx, upper calyx, proximal ureter, mid ureter, distal ureter), stone size (maximum longitudinal dimension), body mass index (BMI), and stone Hounsfield unit (HU) values. Patients were categorized into two groups: single-session and multiple-session treatment. Results In the univariate model, factors such as age, BMI, distal ureter, renal pelvis, mid-calyx stone localization, stone size, and stone HU value showed a significant ( p < 0.05) effect in distinguishing between single-session and multiple-session groups. Stone size and HU values were significantly higher ( p < 0.05) in the multiple-session group compared to the single-session group. In the multivariate model, age, stone size, and HU value emerged as significant independent factors ( p < 0.05) in differentiating between single-session and multiple-session treatments. Conclusion Several factors influencing the success of ESWL also affect the number of sessions required. BMI, age, stone size, stone HU value, and certain stone locations are key determinants of the number of ESWL sessions.

Objective The aim of this study is to construct a post-operative nomogram for renal pelvic cancer, thereby addressing a gap in the current academic literature and offering a valuable tool for predicting patient outcomes following surgical intervention. Methods This study utilized data from the Surveillance, Epidemiology, and End Results program (2004–2017) to analyze patients diagnosed with renal pelvic cancer who underwent surgery. Variables analyzed included demographics, histology, grade, stage, and treatment modalities. Statistical analysis involved Kaplan-Meier and Cox models, developing a nomogram to predict 1-, 3-, and 5-year cancer-specific survival (CSS), validated through receiver operating characteristic (ROC) curves, calibration, and decision curve analysis (DCA) to assess clinical utility. Results The training cohort consisted of 1,486 patients, and the validation cohort comprised 637 patients. Factors affecting CSS, analyzed through univariate and multivariate models, included age, histology, cancer grade, stage, and treatment modalities. The developed nomogram, tested via ROC curves and calibration plots, showed robust predictive accuracy for CSS across both cohorts, with its clinical utility demonstrated through DCA. Conclusion Age, histology, grade, and stage were significant risk factors for CSS in renal pelvic urothelial carcinoma post-surgery. A nomogram utilizing these factors aids in evidence-based clinical decision-making.

Objective Autophagy serves as a protective mechanism in response to mechanical stress during OTM. However, the role of ATG7, a key regulatory gene in autophagy, in modulating periodontium remodeling during OTM remains unclear. This study aims to investigate the potential modulation of periodontium remodeling by ATG7 under compression force. Materials and Methods HPDLSCs and a rat OTM model were used as in vitro and in vivo systems to study the effect of compressive stress on autophagy and osteoclast-related markers. To investigate the role of ATG7, hPDLSCs with ATG7 knockdown and ATG7 +/− rats were used in this study. Results Compression force activates autophagy and increases the RANKL/OPG ratio. ATG7 knockdown significantly suppresses autophagy in hPDLSCs, while the RANKL/OPG ratio is markedly elevated. Under compression stress, hPDLSCs-siATG7 markedly enhanced RANKL/OPG expression. In the rat OTM model, autophagy was significantly activated in the periodontium on the compression side. Compared to wild-type SD rats, ATG7 +/− rats exhibit reduced autophagy-related protein expression, an increased RANKL/OPG ratio, and accelerated tooth movement. Conclusions Under compression force, inhibition of ATG7 expression significantly increases the RANKL/OPG ratio both in vivo and in vitro , which is accompanied by an increased rate of orthodontic tooth movement.

Background Cancer stemness, hypoxia, and glycolysis collectively influence colorectal cancer (CRC) progression. However, the intricate relationships among these factors remain incompletely understood. Methods This study (1) explored hypoxia and glycolysis-related genes (HGRGs) in CRC by mRNA stemness index (mRNAsi), analyzed the gene expression profiles from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, (2) established a Cox-prognostic model based on single-sample gene set enrichment analysis, differentially expressed gene analysis, weighted gene co-expression network analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses, and (3) assessed the predictive accuracy of the model. Decision curve analysis (DCA) was employed to determine the clinical utility of the model. Results Ten HGRGs were selected based on mRNAsi to create the LASSO model. High-risk CRC patients in the TCGA dataset displayed unfavorable clinical outcomes and responses to immunotherapy. Consensus cluster analysis revealed two distinct colon adenocarcinoma/rectal adenocarcinoma clusters, with patients in cluster 2 having a worse prognosis compared to patients in cluster 1. A five-gene prognostic nomogram was developed through univariate and multivariate Cox regression analyses, with DCA confirming its accuracy. Conclusions This innovative prognostic model, incorporating ALDOB , AQP1 , IL1A , PHGDH , and PTGIS , is highly accurate in predicting patient survival.

Background Sepsis-associated encephalopathy (SAE) remains a major unmet clinical need, due to the lack of effective treatments. Although glutathione (GSH) is known for its antioxidant properties, its specific neuroprotective role via modulation of inflammatory pathways in SAE remains poorly understood. Methods Using a lipopolysaccharide (LPS)-induced murine sepsis model, we examined GSH’s effects through comprehensive behavioral assessments, histopathological analysis, and molecular profiling. Mice were pretreated with GSH prior to LPS challenge, and outcomes were assessed across multiple parameters. Key results This study reveals that GSH pretreatment significantly improved survival rates by 10% ( p < 0.01) and significantly alleviates neurological deficits in a murine model of sepsis. Behaviorally, GSH reversed depression-like symptoms, boosting locomotor activity ( p = 0.009) and reducing immobility ( p < 0.05). Histopathological analysis showed that GSH preserved hippocampal structure, maintaining 40% more viable neurons in CA1/DG regions ( p < 0.05). Mechanistically, GSH exerts dual neuroprotective actions: it robustly suppresses NF-κB signaling via inhibition of p65 nuclear translocation and downregulation of IL-1β and IL-6, while simultaneously activating the PKA/CREB pathway revealing a previously unrecognized mechanism of action. Conclusion This study provides the first evidence of GSH’s dual mechanism action in SAE, establishing it as a promising multi-target therapeutic candidate. These findings open new avenues for developing effective SAE interventions targeting both inflammatory and neuroprotective pathways.

Background Ferroptosis, a type of iron-dependent lipid peroxidation-induced neuronal death, has been strongly implicated in the initiation and progression of various neurological disorders, including neurodegenerative diseases and central nervous system (CNS) injuries. Although significant research efforts have been devoted to this area, most available therapeutic strategies remain largely ineffective due to the complex pathophysiology of these conditions. Moreover, the mechanisms underlying neuronal ferroptosis are not yet fully elucidated. Methods To investigate the role of FAHD1 in neuronal ferroptosis, bioinformatic analyses and cellular experiments were performed. Immunofluorescence and dot blot analyses were employed to explore the effects of FAHD1 overexpression on R-loop formation. Additionally, western blotting was used to assess alterations in the expression of cGAS–STING pathway-related proteins resulting from FAHD1 overexpression. Results Our results demonstrate that FAHD1 expression is significantly downregulated in primary neurons subjected to oxidative stress. Furthermore, ferroptosis appears to be a major contributor to neuronal damage triggered by oxidative stress. Overexpression of FAHD1 significantly reduced reactive oxygen species accumulation and R-loop formation, preserved genomic stability, and suppressed neuronal ferroptosis by inhibiting activation of the cGAS–STING pathway. Conclusion FAHD1 is a critical regulator of neuronal ferroptosis and may serve as a potential therapeutic target for the treatment of neurodegenerative diseases and CNS injuries.

Background and aim Few studies identified the role of the placenta in birth weight. We aimed to explore the connection between placenta weight, morphology, and term low birth weight (TLBW). Methods This was a case–control study of neonates born at ≥37 weeks’ gestation enrolled in a general hospital from January 2018 to November 2022. Cases (<2,500 g) identified via birth certificates or medical records were matched with controls on the basis of date of birth, gestational age, sex, and maternal age. A nomogram predictive model was constructed based on logistic regression, using placenta parameters and perinatal information. Results A total of 290 neonates (115 with diagnosed TLBW and 175 controls) were determined. There were no significant differences between the two groups concerning gestational age (265.5 ± 5.4 vs 266.3 ± 5.3 days, P = 0.1397), gender, and maternal age at delivery (32.0 ± 3.5 vs 32.1 ± 3.1 years, P = 0.867). The placenta weight (479.0 ± 80.1 vs 597.1 ± 83.1 cm), length (16.3 ± 2.1 vs 18.8 ± 2.0 cm), width (14.3 ± 2.1 vs 16.9 ± 2.0 cm), and thickness (2.3 ± 0.5 vs 2.4 ± 0.4 cm) in the TLBW group were much lower than those in the control group (all P < 0.001). Univariate predictors of TLBW included smaller placental weight, length, width, thickness, volume, and surface area. When put into a multivariate model, placental weight (aOR for per 10 g increase: 0.89; 95% CI: 0.84–0.94) and width (aOR for per 1 cm increase: 0.69; 95% CI: 0.54–0.88) remained to be independent predictors even after controlling for relevant confounders. The odds of TLBW increased when placental weight was below the 50th percentile (aOR: 5.08, 95% CI: 2.59–9.95). Placental width below the 50th percentile was significantly associated with an increased risk of TLBW (aOR: 6.57, 95% CI: 2.73–15.82). Conclusions Placental weight and width were found to be associated with TLBW. Further studies focusing on placental function, histology, and pathophysiology are needed to better understand the underlying mechanisms influencing fetal growth and TLBW.

Background Sjögren’s syndrome (SS) is a chronic autoimmune disorder primarily affecting the exocrine glands, leading to symptoms such as dry eyes and mouth, joint pain, fever, and neurological complications. The etiology of SS involves a complex interplay of hormonal, immune, environmental, and genetic factors. Previous studies have identified associations between SS susceptibility and polymorphisms in genes such as HLA-II, STAT4, BAFF, and TNIP1. However, these associations have not been explored in the Turkish population. Objective This study aimed to investigate the association between four specific single nucleotide polymorphisms (SNPs) – rs1130380, rs7574865, rs9514828, and rs17728338 – and susceptibility to SS in a Turkish cohort. Methods A total of 115 SS patients and 40 healthy controls were recruited from Turkey. Genomic DNA was extracted, and genotyping of the four selected SNPs was performed using the polymerase chain reaction – restriction fragment length polymorphism method. Genotypic and allelic distributions were compared between the patient and control groups. Results Significant associations were found between the analyzed polymorphisms and SS susceptibility. Additionally, allele frequency comparisons with global datasets revealed that the risk alleles occur at higher frequencies in the Turkish population compared to European, American, and Asian populations, indicating a potential population-specific genetic predisposition. Conclusion These findings suggest that the SNPs rs1130380, rs7574865, rs9514828, and rs17728338 may contribute to SS susceptibility in the Turkish population. This preliminary evidence supports the need for larger, population-based studies to further elucidate the genetic underpinnings of SS in Turkey.

COVID-19 virus infection can cause disorders of the endocrine system. The aim of this study was to characterize the alterations of nucleotide metabolomic patterns in patients with post-COVID-19 condition (PCC). The study population included 18 patients with PCC alone (PCC-A), 31 patients with PCC combined with type 2 diabetes mellitus (PCC-DM), 20 healthy volunteers (HV), and 20 patients with type 2 diabetes mellitus (DM). Ultraperformance liquid chromatography–mass spectrometry was conducted on plasma metabolites. A total of 116, 178, and 163 differential metabolites were identified in PCC-DM vs PCC-A, PCC-A vs HV groups, and PCC-DM vs DM groups, respectively. Adenine was significantly down-regulated, and purine, thymine, and uracil were significantly up-regulated in the PCC-A group compared with the HV group, and the same results were observed in the PCC-DM group compared with the DM group. Differential metabolites were mainly involved in nucleotide metabolism, especially pyrimidine metabolism in PCC patients. After the arginine stimulation test, cortisol and adrenocorticotropic hormone secretion were reduced in PCC patients. In conclusion, the nucleotide de novo synthesis pathway and the remedial synthesis pathway are seriously damaged in patients with PCC-A, especially in patients with PCC-DM, which leads to the disorder and imbalance of the body cell metabolism pathway.

Objective Transforming growth factor beta (TGF-β) is a key regulator of macrophage polarization, yet its role in high-altitude pulmonary hypertension (HAPH) remains poorly understood. This study aimed to explore the effects of TGF-β on macrophage polarization under high-altitude conditions and elucidate the molecular mechanisms driving macrophage phenotypic changes in HAPH, with potential therapeutic implications. Methods A HAPH rat model was established by exposing rats to a hypoxic environment simulating 5,000 m altitude for 4 weeks. Rats were prophylactically treated weekly with the TGF-β inhibitor SB-431542. Pulmonary artery pressure and right ventricular hypertrophy index were measured to confirm model establishment. Hematoxylin and eosin staining, immunohistochemistry, and western blotting were used to assess TGF-β–Smad2/Smad3 signaling and macrophage polarization. Results The HAPH group showed significantly increased pulmonary artery pressure and right ventricular hypertrophy index compared to controls. These changes were associated with elevated M2 macrophage levels, increased anti-inflammatory cytokines (IL-4 and IL-10), and enhanced TGF-β and Smad2/Smad3 signaling. TGF-β inhibition reversed these effects. Conclusion The TGF-β–Smad2/Smad3 pathway promotes macrophage M2 polarization, driving HAPH progression through anti-inflammatory cytokine release. Inhibiting this pathway reduces M2 polarization and alleviates HAPH in rats, highlighting its therapeutic potential.

Introduction Ultrasound-guided erector spinae plane block (ESPB) was originally developed for the treatment of neuropathic chest pain and has since been used in various thoracic, lumbar, and sacral surgeries. Objective This study aimed to establish whether unilateral or bilateral ESPB is more effective for pain management in laparoscopic cholecystectomy. Materials and methods A total of 54 adult patients undergoing laparoscopic cholecystectomy were divided into three groups: unilateral ESPB, bilateral ESPB, and a control group (no ESPB). The unilateral ESPB group received 20 mL of 0.25% bupivacaine preoperatively at the T8 vertebral level. The bilateral ESPB group received 20 mL of 0.25% bupivacaine to both sides of the vertebra. The control group received no intervention, and all three groups received general anesthesia. Intraoperatively, all patients received 50 mg of dexketoprofen and 1 mg/kg of tramadol. Postoperative tramadol use and visual analog scale (VAS) scores were recorded at 0 min, 30 min, 2 h, 6 h, 12 h, and 24 h. Results Demographic characteristics did not differ significantly between the groups. At the 6 h post-surgery, the VAS scores in the bilateral ESPB group were significantly lower than the control group ( p < 0.001). Total tramadol use in 24 h was significantly lower in the bilateral ESPB group compared with the control group ( p = 0.003). Conclusions Bilateral ESPB could be a valuable component of multimodal analgesia strategies in laparoscopic cholecystectomies.

Aim The aim of this study is to characterize gut microbiome alterations in newly diagnosed subacute thyroiditis (SAT) patients, and identify potential microbial signatures associated with SAT and treatment response. Methods Fecal samples collected from 20 newly diagnosed SAT patients and 20 healthy controls were analyzed using 16S ribosomal RNA gene sequencing. Bioinformatics analysis was performed to assess alpha and beta diversity, taxonomic composition, and differential abundance of gut microbiota between the groups. Correlations between gut microbiome and clinical parameters were also investigated. Results Newly diagnosed SAT patients exhibited significant alterations in gut microbiota composition. There was increased abundance of Escherichia-Shigella , Bifidobacterium , Akkermansia , Veillonella , and Streptococcus , while the abundance of Bacteroidetes , Faecalibacterium , Prevotella , Roseburia , and Ruminococcus were significantly decreased. Prednisolone treatment partially normalized the gut microbiota, with Lactobacillus , Lactobacillaceae , Lactobacillus reuteri , and Prevotella emerging as key biomarkers in post-treatment SAT. Significant correlations were found between specific gut microbiome and clinical markers. Conclusion SAT is associated with distinct gut microbiome alterations, partially reversible with treatment, which suggest a potential role for the gut microbiome in SAT pathogenesis and treatment response.

Aim This study investigates the diagnostic accuracy of five inflammatory biomarkers – delta neutrophil index (DNI); C-reactive protein/albumin ratio (CAR); procalcitonin (PCT); immature granulocytes count (IGc); and hemoglobin, albumin, lymphocyte, platelet score (HALPs) – in detecting acute appendicitis (AA) and identifying the most reliable marker for distinguishing complicated from non-complicated cases. Materials and methods A prospective, cross-sectional study was conducted in a tertiary hospital emergency department, including 100 histopathologically confirmed AA patients and 100 healthy controls. Biomarker levels were analyzed using receiver operating characteristic curves. Sensitivity, specificity, and optimal cut-off values were determined via the Youden index, while logistic regression identified independent predictors of complicated appendicitis (CA). Results DNI exhibited the highest diagnostic accuracy for AA (AUC: 0.87, 95% CI: 0.821–0.919, p < 0.001) with 92% specificity and 69% sensitivity at a cut-off of 71.88. CAR (AUC: 0.853) and PCT (AUC: 0.852) showed similar performance, whereas IGc (AUC: 0.695) and HALPs (AUC: 0.627) were less effective. DNI also outperformed the Alvarado score in predicting CA (AUC: 0.698 vs 0.626) and was an independent predictor (OR: 3.18, 95% CI: 1.40–7.24, p = 0.006). Conclusions DNI demonstrated superior diagnostic performance for AA and was the most reliable marker for identifying CA. Its integration into clinical practice may enhance early diagnosis and reduce unnecessary surgeries, improving outcomes.

Cancer is the second biggest cause of death after cardiovascular disorders and its incidence is rising significantly. One out of every ten cancer-related deaths is caused by colon cancer. The increasing incidence calls for creating focused therapeutic strategies with fewer adverse effects than traditional clinical techniques like radiation, chemotherapy, and immunotherapy. In this study, we evaluated the anticancer effects and mechanisms of a synthesized and characterized benzofuran ring-linked 3-nitrophenyl chalcone derivative, [1-(2-benzofuranyl)-3-(3-nitrophenyl)-2-propen-1-one], on colon cancer cells (HCT-116 and HT-29) as well as healthy colon cells (CCD-18Co). Cell viability analyses using the sulforhodamine B assay demonstrated that the IC₅₀ values after 48 h of treatment were 1.71 µM for HCT-116, 7.76 µM for HT-29, and higher than 10 µM for CCD-18Co cells. These results indicate a selective cytotoxic effect on cancer cells an essential criterion for evaluating anticancer compounds. Triple fluorescence staining, flow cytometry caspase 3/7 activity, along with protein expression analyses, confirmed that the compound induces apoptosis in both cancer cell lines. At IC₅₀ values, the derivative activated DR-4 -mediated apoptosis at the membrane and BCL-2 -mediated apoptosis intracellularly. Moreover, treatment with 12.5 µM of the compound for 24 h, corresponding to a cell cycle time, statistically significantly arrested the cell cycle at the G0/G1 phase. In addition, it inhibited cell migration and colony formation in a dose-dependent manner, starting from values as low as 1.56 µM. Additionally, the binding affinity of the derivative with target proteins was determined using artificial intelligence-assisted molecular modeling analysis. Collectively, these findings highlight the potential of this 3-nitrophenyl chalcone derivative as a promising candidate for the development of novel therapeutic agents against colon cancer. Graphical abstract

Despite significant advances in the diagnosis and treatment of gastric cancer (GC), its incidence and mortality remain high worldwide. Therefore, finding new anticancer drugs or treatment strategies for GC is crucial. The valdien ligand, which is not soluble in water, has demonstrated potential anticancer effects on cancer. This study highlights a water-soluble derivative of the H2valdien ligand derivatives, named H2valdien3, which can inhibit the proliferation of GC by arresting the cell cycle and inducing apoptosis. Initially, the inhibitory effects and cytotoxicity of H2valdien3 on the growth of AGS and MKN45 cells were evaluated using MTT assays. Microscopic observations revealed that H2valdien3-treated AGS and MKN45 cells exhibited deteriorated morphology. Hoechst fluorescent staining and flow cytometry results further demonstrated that H2valdien3 promotes apoptosis and arrests the cell cycle in GC cells. Additionally, the anticancer mechanism of H2valdien3 was found to involve the β-catenin/c-myc pathway. In vivo experiments showed that H2valdien3 inhibited GC proliferation without significantly affecting the weight of the mice. These findings suggest that the transformed H2valdien3 has potential anticancer properties with minimal side effects for GC treatment.

Background Papillary thyroid carcinoma (PTC) generally exhibits favorable prognosis; however, a subset of patients remains at risk for recurrence. Serine protease 2 (PRSS2) was an oncogenic factor in several solid tumors, yet its expression profile and functional role in PTC remain poorly defined. This study aimed to investigate the expression level of PRSS2 in PTC and its prognostic significance, as well as explore its potential involvement in immune regulatory mechanisms. Methods PTC specimens from thyroidectomy patients were analyzed by transcriptomic analysis, quantitative real-time PCR, and immunohistochemistry. Differential gene expression and survival analyses were performed by integrating data from TCGA and GEO databases. Pearson correlation analysis was utilized to evaluate associations between PRSS2 and immune-related genes. Results PRSS2 was upregulated in PTC tissues. High PRSS2 expression was associated with better survival (HR = 3.253; 95% CI: 1.155–9.160), especially in patients aged ≥62 and stage II/III. Patients with low PRSS2 and high BRAF expression exhibited a markedly reduced 5-year overall survival rate. PRSS2 also showed significant positive correlations with multiple immune-related genes, including a moderate to strong correlation with T-cell receptor beta variable ( TRBV ) region genes ( R = 0.58–0.72), CD40 , and transforming growth factor beta-stimulated clone 22 domain 1. Conclusions PRSS2 is upregulated in PTC and is associated with favorable prognosis. Its association with TRBV and other immune-related genes suggests a correlation with tumor immune microenvironment. Further studies are needed to elucidate the biological functions of PRSS2 in PTC and to assess therapeutic potential.

Background Some observational studies have reported that sodium–glucose cotransporter 2 (SGLT2) inhibitors may have an impact on psychiatric disorders. This Mendelian randomization (MR) study aims to explore the causal relationship between SGLT2 inhibition and five types of psychiatric disorders. Methods Genetic variants associated with the SLC5A2 gene and glycated hemoglobin were selected from the eQTLGen Consortium and Genotype-Tissue Expression datasets. Type 2 diabetes served as a positive control in the application of MR and colocalization analyses to investigate potential causal relationships between SGLT2 inhibition and depression, anxiety disorder, schizophrenia, obsessive-compulsive disorder, and bipolar affective disorder. The impact of glycated hemoglobin on psychiatric disorders was additionally analyzed. Results SGLT2 inhibition was associated with an increased risk of anxiety disorder, obsessive-compulsive disorder, and bipolar affective disorder. The effect of SGLT2 inhibition on depression did not reach Bonferroni-corrected significance levels. No association was found between SGLT2 inhibition and schizophrenia. Conclusions This study provides genetic evidence supporting that SGLT2 inhibitors increase the risk of obsessive-compulsive disorder, anxiety disorder, and bipolar affective disorder.

Background and aim Alcohol consumption is a major public health issue, linked to a wide range of physical, psychological, familial, and social harms, as well as increased rates of violence, accidents, and mortality. The aim of this study is to evaluate the effectiveness of a motivational interviewing program in reducing alcohol consumption patterns among Thai patients. Methods This quasi-experimental study included a control group (CG) and an experimental group (EG), each consisting of 30 patients. Data were collected using a structured questionnaire and analyzed with SPSS, utilizing both descriptive and inferential statistical methods. Results The majority of patients in the CG were aged 45–60 years, whereas the majority in the EG were aged 25–44 years. The intervention involved 4 sessions over 8 weeks motivational interviewing program (MIP). The mean AUDIT scores in the CG were 24.10 before the intervention and 22.90 after, while in the EG, scores decreased from 22.63 to 19.33. The interaction between the factors (CG and EG) before the intervention did not have a significant effect (Multivariate Analysis of Variance, MANOVA: p = 0.255), but was significant after the intervention (MANOVA: p = 0.009). Conclusion MIP had a significant effect on reducing alcohol consumption among patients of the EG.

Background Thyroid cancer is the most common malignancy of the endocrine system, and effective treatments for metastatic disease are still lacking. Targeting both glycolysis and oxidative phosphorylation (OXPHOS) simultaneously represents a novel approach to cancer therapy. While polyphyllin has been shown to modulate cellular metabolism in various cancers, its role in thyroid cancer remains unexplored. Purpose This study aimed to explore the antitumor effects and underlying mechanisms of polyphyllin in thyroid cancer. Methods Thyroid cancer cells were treated with varying concentrations of Polyphyllin I, II, VI, and VII. Cell viability was assessed using the CCK-8 assay to identify the most effective polyphyllin compound and its optimal dosage. Colony formation and EdU incorporation assay were performed to evaluate cell proliferation, while Transwell assays were used to assess cell invasion. Cell migration ability was examined using the wound healing assay. The effect of Polyphyllin II on OXPHOS was evaluated using an extracellular oxygen consumption rate (OCR) assay kit. Glucose uptake, lactate production, glycolysis-related protein expression, and the extracellular acidification rate (ECAR) were measured to assess the effects of Polyphyllin II on glycolysis in thyroid cancer cells. Flow cytometry and western blotting were conducted to detect apoptosis. Results Polyphyllin I, II, VI, and VII all inhibit the proliferation of thyroid cancer cells, with Polyphyllin II showing the most potent inhibitory effect. Polyphyllin II suppresses cell proliferation, invasion, and migration of thyroid cancer cells, while also promoting apoptosis. Mechanism studies reveal that Polyphyllin II inhibits extracellular OCR, basal respiration, maximum respiration, ATP-linked respiration, spare respiration capacity, glucose uptake, lactate production, glycolytic rate-limiting enzymes, and the ECAR in thyroid cancer cells. Conclusion Polyphyllin II simultaneously inhibits glycolysis and OXPHOS, thereby suppressing the invasion, migration, and proliferation of thyroid cancer cells, while also promoting apoptosis.

Objective This study investigates the association between serum SLC31A1, a copper death-promoting factor, and clinicopathological features/prognosis in papillary thyroid carcinoma (PTC). Methods A cohort of 250 PTC patients was stratified into good ( n = 205) and poor ( n = 45) prognosis groups. Clinicopathological parameters (age, sex, tumor diameter, differentiation, TNM stage, thyroid exocapsular invasion, lymph node metastasis) and serum SLC31A1 levels (measured via ELISA) were analyzed. Patients were further categorized into high/low SLC31A1 expression groups based on median values. Prognostic correlations were evaluated using Kaplan–Meier survival analysis, Cox regression, and receiver operating characteristic (ROC) curve assessment. Results Elevated serum SLC31A1 levels were significantly associated with poor prognosis, advanced TNM stages (III/IV), poor differentiation, thyroid exocapsular invasion, and lymph node metastasis. Multivariate Cox analysis identified high SLC31A1 as an independent predictor of poor prognosis (HR = 1.235, 95% CI 1.158–1.317). ROC analysis demonstrated strong predictive accuracy for SLC31A1 in prognosis assessment (AUC = 0.859). Conclusion High serum SLC31A1 expression correlates with aggressive clinicopathological features and independently predicts adverse outcomes in PTC patients, suggesting its potential as a prognostic biomarker for clinical stratification.

Objective To investigate the role and underlying mechanisms of colony-stimulating factor 2 (CSF2) in the progression of kidney renal clear cell carcinoma (KIRC). Methods Transcriptomic and clinical data from The Cancer Genome Atlas were analyzed to assess the correlation between CSF2 expression, clinicopathological features, and patient prognosis. A neutrophil–tumor co-culture system was established to examine the effects of CSF2 on neutrophil polarization, tumor cell proliferation, migration, apoptosis, and autophagy. Protein expression was evaluated by flow cytometry, Western blot, and immunofluorescence. PD-L1 knockout and autophagy inhibitors (3-methyladenine and chloroquine) were used to explore regulatory mechanisms. Results CSF2 expression was significantly upregulated in KIRC tissues and was positively associated with advanced tumor stage and poor prognosis. In vitro , CSF2 promoted neutrophil polarization toward the tumor-supportive N2 phenotype and enhanced the proliferation and migration of renal cancer cells while inhibiting apoptosis and reactive oxygen species production. Additionally, CSF2 upregulated PD-L1 expression in tumor cells and activated autophagy by increasing LC-3, Beclin1, and ATG7 levels. These effects were reversed by PD-L1 knockout or treatment with the autophagy inhibitor 3-methyladenine. Conclusion CSF2 promotes KIRC progression through PD-L1–mediated neutrophil polarization and autophagy activation, representing a potential therapeutic target.

Objective Thrombocytopenia induced by proton pump inhibitors (PPIs) is a relatively uncommon adverse effect of this widely prescribed class of drugs. The objective of this study is to investigate the clinical features of PPIs-induced thrombocytopenia based on published case reports. Methods We searched the PubMed, Web of Science, Scopus, China National Knowledge Infrastructure, Wanfang Data, and Chinese VIP databases from inception to August 2024 to identify reported cases of thrombocytopenia associated with PPIs use. Clinical data such as patient demographics, drug use information, adverse reactions, and outcomes were extracted and analyzed. Results Overall, 16 publications describing 18 cases (12 males and 6 females) were included in this study, comprising a neonate and 17 adults with a median age of 62 years (range 23–98). The PPIs associated with thrombocytopenia included pantoprazole (11 cases), lansoprazole (4 cases), omeprazole (2 cases), and esomeprazole (1 case). The median time to symptoms onset was 3 days (range 2–7) after the initiation of PPI therapy. After discontinuation of PPIs and interventions such as platelet transfusion, 11 patients achieved recovery, and the remaining 7 patients experienced symptomatic improvement. Conclusion Thrombocytopenia induced by PPIs appears to be a rare adverse event. Clinicians should enhance their awareness when evaluating potential cases of thrombocytopenia. Once PPIs are suspected, immediate discontinuation of the drugs and initiation of appropriate treatments are recommended.

Background and aim The study used a sequential qualitative–quantitative research design to develop a survey tool that explores the current situation and influencing factors of community nurses’ research ability. Methods The qualitative research developed the Chinese Community Nurses Research Ability Tool (CCN-RAT) through face-to-face interviews. The quantitative research tests the current situation and influencing factors of research ability among community nurses. One-way ANOVA and Multiple Linear Regression were used to analyze the results. Results The Cronbach’s α was found to be 0.993, and the Subject-Content Validity Index was 0.99 using CCN-RAT. Most of the community nurses had a low to moderate level of research ability. Age (95%CI: 1.812–9.533, P = 0.004), educational attainment (95%CI: 4.667–11.660, P < 0.001), working experience year (95%CI: 0.274–1.0410, P = 0.001), number of participants in research projects (95%CI: 0.239–11.130, P = 0.041), number of published articles in Chinese core journal or SCI (95%CI: 19.354–36.969, P < 0.001), and number of participants in research training (95%CI: 18.289–28.218, P < 0.001) were significant influencing factors on research ability among community nurses. Conclusion CCN-RAT could help nurses, educators, students, and other populations to better understand the current situation and influencing factors of research ability, which could provide targeted research training to improve research ability for public health staff.

The increased use of next-generation sequencing in clinical genetic testing has resulted in the identification of several genetic variations with possible therapeutic implications. We developed OKAIN (https://szcube.origimed.com), an algorithm tool that assesses clinically actionable mutations using a precision oncology knowledge database. OKAIN employs a weighted evidence analysis system to deliver final clinical annotation outcomes for intricate variations. As of now, OKAIN has amassed over 100,000 variants in 1,239 cancer-associated genes, encompassing 12,409 entries of therapeutic evidence in 471 genes. This collection highlights 2,600 Level A evidence entries in 66 genes, with 864 entries derived from the National Medical Products Administration labels or Chinese guidelines. OKAIN acts as a precision oncology knowledge base for the assessment of clinically actionable alterations, integrating exhaustive data related to cancer-associated genomic variants and therapeutic efficacy. Analyzing patient variants with OKAIN reveals more actionable targeted therapy or immunotherapy options, potentially improving treatment outcomes.

Objective This study aimed to investigate the relationship between serum carbohydrate antigen 50 (CA50), carbohydrate antigen 242 (CA242), and serum amyloid A (SAA) levels and clinical pathological features and prognosis in pancreatic cancer (PC) patients. Methods A total of 163 PC patients were divided into a survival group ( n = 43) and a deceased group ( n = 120). Serum levels of CA50, CA242, and SAA were measured, and patients were categorized into high- and low-expression groups based on median values. Relationships between marker expression, clinical features, and prognosis were analyzed using Cox regression, receiver operating characteristic (ROC) analysis, and Kaplan–Meier curves. Results Serum CA50, CA242, and SAA levels were significantly higher in the deceased group than in the survival group (all P < 0.001). High CA50 was linked to advanced TNM stage and distant metastasis; high CA242 to advanced TNM stage and lower differentiation; and high SAA to advanced TNM stage and distant metastasis (all P < 0.05). Multivariate Cox regression showed that advanced TNM stage (hazard ratio [HR] = 1.499, 95% confidence interval [CI] = 1.003–2.238, P = 0.048), distant metastasis (HR = 1.693, 95% CI = 1.157–2.478, P = 0.007), high CA50 (HR = 1.041, 95% CI = 1.019–1.064, P < 0.001), high CA242 (HR = 1.044, 95% CI = 1.018–1.070, P < 0.001), and high SAA (HR = 1.096, 95% CI = 1.044–1.151, P < 0.001) were independent risk factors for poor prognosis. ROC analysis showed that the combined detection of CA50, CA242, and SAA had the highest predictive value for poor prognosis (AUC = 0.989, sensitivity = 93.33%, specificity = 100%), which was significantly superior to single-marker detection (CA50: AUC = 0.872, sensitivity = 78.33%, specificity = 88.37%; CA242: AUC = 0.905, sensitivity = 74.17%, specificity = 88.37%; SAA: AUC = 0.871, sensitivity = 80.00%, specificity = 83.72%; all P < 0.001 vs combination). Kaplan–Meier curves revealed higher mortality risk in high-expression groups. Conclusion Serum CA50, CA242, and SAA levels are closely associated with PC patients’ clinical features and prognosis. Their combined detection is a valuable tool for assessing poor prognosis in PC.

Background Hypoxia and glycolysis play crucial roles in tumor progression, yet their association with kidney renal clear cell carcinoma (KIRC) remains unclear. Here, a novel prognostic model was developed with hypoxia–glycolysis-related genes (HGRGs) in KIRC, providing insights to elucidate the aforementioned uncertainties. Methods Transcriptomic information and clinical characteristics of KIRC were acquired from The Cancer Genome Atlas Program, ArrayExpress database, and Gene Expression Omnibus. Significant HGRGs were identified, and a prognostic model was constructed. We performed enrichment analysis, tumor mutational burden (TMB), tumor microenvironment), and drug sensitivity analyses to elucidate potential mechanisms of HGRGs. Results The prognostic model based on five HGRGs (ADORA2B, TGFA, FBP1, HK3, PDHB) effectively predicted the clinical outcome. The nomogram, which integrates a prognostic model and clinical information, demonstrated superior performance. Low-risk patients were enriched in fatty acid metabolism and peroxisome pathways, exhibited higher immunotherapy responsiveness, and showed greater sensitivity to Gefitinib and Afatinib. High-risk patients exhibited activation of inflammatory and profibrotic pathways, an elevated TMB, immunosuppressive microenvironments, and greater sensitivity to Topotecan and Irinotecan. RT-qPCR validated the expression of HGRGs across selected cell lines. Conclusions The prognostic model derived from five HGRGs demonstrates excellent clinical value in predicting prognosis and guiding therapeutic strategies in KIRC.

Introduction Cell membrane-derived nanovesicles, particularly those originating from red blood cells (RNVs), have garnered considerable attention as innovative drug delivery vehicles in oncology, owing to their exceptional biocompatibility, immune evasion, and prolonged systemic circulation. Nevertheless, their inherently poor tumor-targeting efficiency and nonspecific biodistribution present major obstacles to their therapeutic translation. Objectives This study sought to functionalize RNVs with a diverse array of tumor-targeting ligands – cRGD, transferrin (TRF), folic acid (FA), GE11, and RVG29 – and to systematically compare their tumor-homing efficiency, biodistribution, and biosafety in a breast cancer model. Results Functionalized RNVs exhibited markedly enhanced tumor affinity relative to unmodified vesicles in both in vitro and in vivo settings. Among the engineered formulations, RNV@cRGD achieved the most pronounced intratumoral accumulation and cellular uptake, followed sequentially by RNV@GE11, RNV@TRF, RNV@FA, and RNV@RVG29. Fluorescence imaging corroborated the superior tumor selectivity of engineered constructs, all of which also demonstrated robust stability and negligible off-target toxicity in murine models. Conclusion This work presents systematic comparative evaluation of ligand-engineered RNVs, underscoring cRGD as the most potent targeting moiety for breast cancer. These findings illuminate critical design principles for the rational development of tumor-directed RNV-based drug delivery systems and strengthen the translational promise of biomimetic nanocarriers for clinical oncology.

Some of the millions of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have developed new sequelae after recovering from the initial disease, termed post-acute sequelae of coronavirus disease 2019 (PASC). One symptom is anxiety, which is likely due to three etiologies: brain structural changes, neuroendocrine disruption, and neurotransmitter alterations. This review provides an overview of the current literature on the pathophysiological pathways linking coronavirus disease 2019 to anxiety, as well as the possible mechanisms of action in which an increasingly scrutinized treatment method, enhanced external counter-pulsation (EECP), is able to alleviate anxiety. SARS-CoV-2 triggers increased inflammatory cytokine production, as well as oxidative stress; these processes contribute to the aforementioned three etiologies. The potential treatment approach of EECP, involving sequenced inflation and deflation of specifically-placed airbags, has become of increasing interest, as it has been found to alleviate PASC-associated anxiety by improving patient cardiovascular function. These functional improvements were achieved by EECP stimulating anti-inflammatory and pro-angiogenic processes, as well as improving endothelial cell function and coronary blood flow, partially via counteracting against the negative effects of SARS-CoV-2 infection on the renin–angiotensin–aldosterone system. Therefore, EECP could promote both psychosomatic and cardiac rehabilitation. Further research, though, is still needed to fully determine its benefits and mechanism of action.

Background Diabetes-related cognitive impairment is increasingly recognized as a significant complication, profoundly impacting patients’ quality of life. This review aims to examine the pathophysiological mechanisms, clinical manifestations, risk factors, assessment and diagnosis, management strategies, and future research directions of cognitive impairment in diabetes. Methodology A comprehensive literature search was conducted using PubMed, Medline, and other medical databases to identify, review, and evaluate published articles on cognitive impairment in diabetes. The search focused on studies examining pathophysiology, clinical presentations, risk factors, diagnostic approaches, and management strategies. Results The review of current literature revealed that chronic hyperglycemia, insulin resistance, and vascular factors are major contributing factors to cognitive deficits in diabetes. Clinical manifestations include impairments in attention, memory, executive function, visuospatial abilities, and language. Risk factors encompass disease duration, glycemic control, presence of complications, age, education level, and comorbidities. Assessment tools include cognitive screening instruments, neuropsychological testing, and neuroimaging techniques. Management strategies involve glycemic control optimization, lifestyle modifications, cognitive training, and pharmacological interventions. Conclusion This review highlights the significant prevalence and impact of cognitive impairment in diabetes, resulting from complex metabolic and vascular disturbances. Early detection and multifaceted interventions are crucial for preserving cognitive function and improving patient outcomes. Future research should focus on neuroprotective strategies, biomarker identification, and personalized approaches. Collaborative efforts between clinicians and researchers are essential to effectively address this growing healthcare challenge and enhance the quality of life for individuals with diabetes-related cognitive impairment.

Introduction/objective Gestational diabetes mellitus (GDM) influences adverse maternal and fetal outcomes. Nutritional therapy and exercise are the first steps to maintain normal glucose levels. During pregnancy, metabolic status influences placental development. Methods This systematic review focused only on the morphology of the placenta and its microscopic changes in GMD under dietary therapy. A systematic search was performed on the main databases from inception to September 2024 (PROSPERO ID: CRD42024581621). Only original articles on GDM in diet and exercise treatment that reported at least one outcome of interest (microscopic features and macroscopic morphology of the placenta) were included. Results A total of 716 studies were identified, and nine met the inclusion criteria. The analysis confirmed that despite dietary control, some morphological changes in the placenta, including villus immaturity, chorangiosis, and fibrinoid necrosis, occurred at a different rate. In addition, the included studies reported an increase in placental weight in the diet-controlled GDM group. Conclusion Therefore, the results of the present qualitative analysis show that pregnant women with diet-controlled GDM, despite adequate glycemic control, abnormal placental development may persist. Our findings remark on the importance of the correct diet-managed GDM pregnancy monitoring due to the placental morphology abnormalities related to GMD.

Background The immune system is closely related to hypertension. Hypertension is an immune disorder to a certain extent, and inflammation is the basis of abnormally elevated blood pressure (BP). The accumulation of T cells and their cytokines can increase BP and end organ damage. T cells are activated by antigen-presenting cells of the innate immune system or by the influence of a high-sodium diet, the self-environment, or the gut microbiota. These cells produce inflammatory factors and cytokines, such as interleukin-17A (IL-17A) in T helper 17 cells, causing vascular inflammation, hypertension, and target organ damage Methods In this article, we provide an insightful review of the research progress regarding the role of IL-17A in the pathogenesis of hypertension and its effects on different organs while emphasizing the role of IL-17A and its mediated functions in the kidneys, brain, intestines, and vascular system in the development and progression of hypertension. Results At the organ level, IL-17A is involved in the development and progression of hypertension in the kidneys, brain, intestines, and blood vessels, interacting with multiple signal pathway. Conclusions These findings have significant implications for developing future immunomodulatory therapies, which may lead to the development of potential treatments for hypertension.

Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and β-cell dysfunction. A hallmark of T2DM pathology is the accumulation of toxic amyloid polypeptides in and around pancreatic islet cells, leading to the progressive loss of β-cell populations. Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-amino acid peptide hormone primarily produced by pancreatic β-cells. hIAPP aggregation and amyloid formation are strongly correlated with β-cell death and disease severity in T2DM patients. Objectives This article aims to review the current research progress on the correlation between hIAPP and T2DM, focusing on the molecular mechanisms and potential therapeutic strategies. Methods We conducted a comprehensive literature review covering recent studies on the molecular structure, physiological function, and pathological mechanisms of hIAPP. Key areas include biosynthesis, monomer structure, and the formation of hIAPP fiber structures. Additionally, we examined the mechanisms of hIAPP-induced β-cell death, including oxidative stress (OS), endoplasmic reticulum stress (ERS), impaired cell membrane and mitochondrial functions, and inflammatory factors. Results Our review highlights the critical role of hIAPP in the pathogenesis of T2DM. Specifically, we found that hIAPP biosynthesis and monomer structure contribute to its physiological functions, while hIAPP aggregation forms toxic amyloid fibers, contributing to β-cell dysfunction. OS, ERS, impaired cell membrane and mitochondrial functions, and inflammatory factors play significant roles in hIAPP-induced β-cell death. There is a strong correlation between hIAPP aggregation and the severity of T2DM, and potential therapeutic approaches using small molecule inhibitors to prevent hIAPP aggregation and fibrosis are discussed. Conclusion Understanding the molecular mechanisms of hIAPP in T2DM provides insights into potential therapeutic targets and preventive strategies. Future research should focus on developing more effective treatments targeting hIAPP aggregation and its downstream effects.

Introduction We sought to determine the efficacy and safety of Bacillus Calmette-Guérin (BCG) combined with mitomycin C (MMC) compared with BCG monotherapy in intravesical therapies for non-muscle-invasive bladder cancer (NMIBC). Methods We followed the recommended PRISMA guidelines for systematic reviews. Systematic literatures were performed on PubMed, EMBASE, Cochrane Library, CNKI, CBM, VIP, Wan Fang, and Clinical Trials.gov. Randomized controlled trials (RCTs) comparing BCG combined with MMC and BCG monotherapy in intravesical therapies for non-muscle-invasive bladder cancer patients were searched until August 1, 2023. Results This meta-analysis included 11 RCTs with a total of 1,349 subjects. Compared with BCG monotherapy, BCG combined with MMC was associated with lower disease recurrence rate (relative risk [RR] 0.66, 95% confidence interval [CI]: 0.56–0.77, P < 0.00001), disease progression rate (RR 0.61, 95% CI: 0.44–0.84, P = 0.003), and disease-specific mortality (RR 0.46, 95% CI: 0.26–0.78, P = 0.004). However, there was a higher incidence of systemic adverse reactions (RR 1.57, 95% CI: 1.22–2.02, P = 0.0004). There was no significant difference in the incidence of local adverse reactions (RR 1.07, 95% CI: 0.95–1.20, P = 0.26) and all-cause mortality (RR 0.80, 95% CI: 0.62–1.03, P = 0.08) between the two groups. Conclusions BCG combined with MMC was associated with a decreased risk of bladder cancer recurrence and disease progression compared with BCG monotherapy. However, there was no significant difference in the incidence of local adverse events and all-cause mortality between the two groups. Due to the limitations of the number and quality of the included studies, more high-quality RCTs are needed to further explore the efficacy and safety of combined therapies.

In robotic surgery, surgical planning and surgical navigation represent two crucial elements, allowing surgeons to maximize surgical outcomes while minimizing the risk of complications. In this context, an emerging imaging technology, namely augmented reality (AR), can represent a powerful tool to create an integration of preoperative 3D models into the live intraoperative view, providing an interactive visual interface rather than a simple operative field. In this way, surgeons can be guided by preoperative imaging during the operation. This makes the surgical procedure more accurate and safer, leading to so-called “precision surgery”. This article aims to provide an overview of developments in the application of AR in robotic general surgery. The integration of this imaging technology in this surgical field is showing promising results. The main benefits include improved oncological outcomes and reduced occurrence of complications. In addition, its application may also be important for surgical education. However, we are still in the initial phase of the experience and some important limitations remain. Moreover, to our knowledge, to date, reports in the literature regarding the integration of AR in robotic general surgery are still very limited. To improve its application, close collaboration between engineers, software developers, and surgeons is mandatory.

Introduction Polyphenols are a group of compounds identified as secondary metabolites of plants, with 8,000 types identified to date. Previous research findings have indicated the potential anti-inflammatory properties of polyphenols, with studies suggesting a reduction in disease risk and therapeutic benefits observed in various diseases, including diabesity, neurodegeneration, cancer, and cardiovascular disease. Objective The objective of this study was to comprehensively analyze the polyphenol composition of extracts of Greek mountain tea (GMT) and wheat germ (WG) and investigate their effects on microcirculation and eicosanoid metabolism. Materials and methods The polyphenol and spermidine composition of GMT and WGE was analyzed using LC–HRMS. Hemodynamic impact of GMT or WG on rat cremasteric arteriole blood flow was measured after compound administration using a laser Doppler blood flow meter. Lipidomic analysis in urine after co-administration of GMT and WGE was measured by LC–HRMS mass spectrometry. Results This study shows that GMT contains large amount of polyphenols, expecially ferulic acid and petunidin. In contrast, in the WG extract we found minimal polyphenol content. Subsequent to the administration of GMT to rats, a significant increase in rat cremasteric arteriole blood flow was observed, while WG extract exhibited minimal change. Following a single oral administration of GMT or WG to mice, 24 h urine was analyzed for eicosanoids. A significant decrease in pro-inflammatory eicosanoids and a substantial increase in anti-inflammatory eicosanoids were observed in the treatment group compared with the control group. Conclusions Given the established role of polyphenol intake in enhancing vascular endothelial function and increasing peripheral blood flow, we suggest that the observed increase in blood flow is a consequence of polyphenols in GMT. In contrast, the enhancement of eicosanoid balance was more pronounced in the WG extract group compared to the GMT group, suggesting that this effect may be attributable to components other than polyphenols present in these fractions.

Background Nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H₂S) are bioactive gasotransmitters implicated in migraine pathophysiology. These gases regulate vascular tone, nociceptive transmission, and inflammatory pathways, playing key roles in both the onset and modulation of migraine. Methods This review synthesizes current evidence on the role of NO, CO, and H₂S in migraine, focusing on their molecular mechanisms, interactions, and potential therapeutic implications. Data from human and animal studies were analyzed to elucidate their contributions to migraine pathogenesis. Results NO is a well-established migraine trigger, with NO donors such as nitroglycerin inducing headache and migraine attacks via cyclic guanosine monophosphate (cGMP)-dependent pathways. CO interacts with NO and cGMP signaling in pain modulation, contributing to central and peripheral nociceptive processing. H₂S exerts dual effects: while its interaction with NO forms nitroxyl (HNO), activating transient receptor potential ankyrin 1 (TRPA1) channels and triggering calcitonin gene-related peptide (CGRP) release; it also demonstrates neuroprotective properties through antioxidant mechanisms and nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Additionally, epigenetic modifications of calcitonin gene-related peptide alpha (CALCA) have been implicated in migraine susceptibility, further supporting the role of these gasotransmitters in disease pathology. Conclusion The interplay between NO, CO, and H₂S represents a critical aspect of migraine pathophysiology, influencing vascular, inflammatory, and nociceptive pathways. Understanding these gasotransmitters’ roles may provide novel therapeutic targets for migraine management, particularly through modulation of TRPA1-CGRP signaling and oxidative stress pathways. Further research is warranted to explore their clinical applications in migraine treatment.

Introduction Herbal products are increasingly being used for their potential to promote oral health. Phytochemicals can act as scavengers of reactive or toxic chemicals, selective growth factors for beneficial oral bacteria, fermentation substrates for beneficial oral bacteria, and selective inhibitors of harmful oral microflora. Plant-derived secondary metabolites encompass a variety of natural products, including alkaloids, polyphenols (including flavonoids and tannins), terpenes, terpenoids, steroids, saponins, quinones, coumarins, glycosides, and carotenoids. Objectives This review explores medicinal plant-based products for preventing and treating oral diseases, offering updated insights into the scientific basis for using herbs as active ingredients in oral health care. Hence, we focused on: (1) phenolic compounds, the most abundant and common phytochemicals and (2) terpenes and terpenoids, the most diverse and widely distributed group in the plant kingdom. Methods Several databases were queried to acquire peer-reviewed studies focusing on the major phytochemical compositions – phenolic compounds, terpenes, and terpenoids – and their oral health benefits. Results The review lists numerous medicinal herbs in various forms and applications for treating dental caries, gingivitis, and periodontitis. Conclusion This review explores the evidence supporting the oral health-promoting effects of specific constituents in herbs with the potential for incorporation into pharmaceutical formulations. Graphical abstract

Introduction The evolution of Laboratory Medicine (LM) has expanded diagnostic and therapeutic horizons, yet ethical concerns pervade its advancements. This article explores the ethical challenges inherent in LM and advocates for a personalist bioethical framework as a guiding principle. It addresses issues such as patient data privacy, healthcare equity, communication of complex analysis results, genetic information management, and conflicts of interest. Objectives The proposed framework emphasizes principles such as the defense of life, freedom, responsibility, totality in therapy, and sociality and subsidiarity, with a focus on human dignity. Results Various bioethical theories address complex ethical issues in medicine and health sciences, often combined to guide clinical practice. This study focuses on personalist bioethics, prioritizing human dignity and intrinsic value, advocating for principles like defense of physical life, freedom, totality in therapy, and sociality. In LM, ethical analysis involves patient care, genetic testing, informed consent, and Artificial Intelligence integration, emphasizing transparency and patient autonomy. Conclusion LM plays a crucial role in healthcare, necessitating ethical considerations amidst technological progress. Upholding ethical frameworks, such as the ethics of good work, can ensure equitable and quality healthcare delivery.

Introduction This study explores the complexities and distinctive traits of end-of-life (EOL) care and assisted suicide in cancer patients across Europe, and the challenges they entail. It analyzes various countries in the Southern, Central, and Northern regions. Legal, ethical, and cultural dimensions of euthanasia are examined. Differences in practices across Europe are highlighted. Materials and methods The aim of this study is to provide an overview of EOL care policies in Europe by delving into the legislative/policy-making approaches of three selected nations, and implications thereof. Results Disparities between regions are identified, to figure out margins for improvement. This includes advocating for a balanced approach that both upholds legal frameworks and respects patient autonomy. By doing so, the ultimate objective is to foster a culture of ethical and empathetic EOL care for cancer patients throughout Europe, ensuring that their needs and preferences are prioritized till the end. Advocacy for a balanced approach is recommended. Conclusion Ultimately, the findings herein presented point to the need for a collaborative effort among policymakers, healthcare providers, and communities to build a more holistic approach to end-of-life care that harmonizes legal regulations with the ethical imperative of respecting individual choice in an environment marked by sensitivity and compassion.

Background There is no umbrella review on maternal risk factors associated with intrauterine growth retardation (IUGR). Therefore, we assessed an umbrella review on maternal risk factors during pregnancy for IUGR. Methods We searched three prominent international databases: PubMed, Scopus, Web of Science, and Cochrane Library. We focused on meta-analyses that examined maternal factors during pregnancy associated with IUGR. The comparison was based on the odds ratio (OR) or related risk ratios reported in the included studies, heterogeneity I 2 , 95% prediction interval, small-study effects, excess significance biases, and sensitive analysis. Results Four risk factors for IUGR include placenta previa with an OR of 1.19, placenta abruption with an OR of 2.06, epilepsy in pregnancy with an OR of 1.28, and hepatitis C virus (HCV) infection with an OR of 1.53 were categorized as having suggestive evidence (Class III). Celiac disease with an OR of 2.48 and mullerian anomaly with an OR of 1.93 were considered risk factors with weak evidence (Class IV). Conclusion Four risk factors for IUGR including placenta previa, placenta abruption, epilepsy in pregnancy, and HCV infection were categorized as having suggestive evidence (Class III). Celiac disease and Mullerian anomaly were considered risk factors with weak evidence (Class IV).

Background Intra-abdominal hypertension (IAH)/abdominal compartment syndrome (ACS) is one of the rarer clinical entities in the pediatric population, carrying a high degree of morbidity and mortality. The focus of this review is on assessing pathophysiological changes of organ systems in pediatric patients with risk factors for the occurrence of IAH/ACS based on the evaluation of diagnostic modalities and therapeutic strategies. Methodology A comprehensive literature search of indexed databases was performed, aiming to identify, review, and evaluate published articles on IAH/ACS. The search was focused on studies examining pathophysiology, risk factors, diagnostic approaches, and management strategies. Results The main risk factors encompass diminished abdominal wall compliance, increased intraluminal and abdominal contents, and capillary leak/fluid resuscitation. Diagnostic tools include clinical and imaging findings, intra-abdominal pressure (IAP) monitoring, and parameters of tissue perfusion. Therapeutic strategies involve non-surgical and surgical management of IAH/ACS in pediatric patients. Conclusion Timely and continuous evaluation of IAP and parameters of tissue perfusion is crucial for the early diagnosis of IAH/ACS and implementing non-surgical procedures, reducing the need for surgical procedures. Future research should focus on the usefulness of advanced non-invasive monitoring technologies and the identification of predictors of increased IAP in the early implementation of personalized therapeutic strategies.

Background Sepsis-associated encephalopathy (SAE) is a complex neurological complication of sepsis involving activation of microglia in the central nervous system (CNS), blood–brain barrier (BBB) dysfunction, neurotransmitter dysfunction, impaired brain metabolism, and mitochondrial dysfunction. Neuroinflammation is a critical component of the pathogenesis. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as a key intracellular signaling pathway, plays a crucial role in regulating neuroinflammation, maintaining the integrity of the BBB, and promoting neuronal cell survival. Objective This review aims to summarize the role of the PI3K/Akt pathway in SAE-associated neuroinflammation and highlights potential therapeutic targets and strategies for its management. Methods We systematically reviewed recent basic and clinical studies on PI3K/Akt signaling pathway in neuroinflammation associated with SAE, as well as the development of pathway-specific agonists and inhibitors. Results The PI3K/Akt pathway serves as a crucial intracellular signaling axis involved in the regulation of neuroinflammatory processes. Accumulating evidence indicates that targeted modulation of this pathway may alleviate neuroinflammation associated with SAE and enhance neurological recovery. Conclusion Targeting the PI3K/Akt pathway represents a promising therapeutic approach for SAE. Advances in the development of specific agonists and inhibitors provide new opportunities for clinical translation and drug discovery in neuroinflammatory conditions.

Background Group B Streptococcus  (GBS) is important since almost 1/3 of pregnant women are colonized with GBS, and as much as 50% passes to the newborns, sometimes resulting in severe neonatal infections; that is why there are mandatory guidelines for antepartum screening for GBS vaginal/rectal colonization. Also, bacteria other than GBS and yeasts may affect newborns; therefore, an increase in the current knowledge and improving the guidelines related to the prediction and prevention of neonatal early-onset infections are needed. Methods A systematic review was performed to investigate risks, types of specimens, sampling methods, media for GBS recovery, identification tests, gestation week for testing, GBS prevalence, sensitivity, specificity, turnover time for cultures, antigen, and molecular-based tests. A literature search was conducted through the Web of Science, Scopus, and PubMed. Results A total of 20 studies were identified with 10,288 patients and 1,334 GBS positive (13%). Eight studies were performed in adequate gestation week and revealed prevalence from 0.2 to 20.8% (conventional tests) and 37 to 45% (molecular tests). In only three studies, vaginal/rectal swab recommended by guidelines was applied. Conclusions The heterogeneity of the detection and identification of GBS reduces the scientific and clinical utility of laboratory-based data, and universal antepartum screening with affordable, high-sensitivity traditional tests is needed.

Introduction Giant borderline ovarian tumours (GBOTs) are rare neoplasms that require meticulous management to prevent high-risk operative complications. The broader goal of this systematic review is to consolidate the existing knowledge on GBOTs by focusing on diagnostic approaches, differential diagnoses, and treatment strategies. Furthermore, the relationship between the clinical features of GBOTs and the types of diagnostic and therapeutic procedures implemented was determined. Materials and methods The publications were analysed for the following data: histopathological type of GBOT; patient’s age; dimensions, weight, and/or volume of the tumour; levels and types of tumour markers determined; types of imaging tests performed; type of treatment applied. Results Twenty-one articles describing the clinical situation of 22 patients met the inclusion criteria for the systematic review. The mean age of the patients included in the analysis was 46.68 years (SD: 19.1 years); the youngest patient was 12, and the oldest was 76 years of age. In the analysed literature, patients most often (81.8%) had the mucinous type of GBOT. In the vast majority of cases (86.36%), based on the analysed literature, the surgical treatment method for the patients was laparotomy. In more than half of the patients (54.55%), the uterus was removed during surgical treatment. In the analysed literature, the hysterectomy procedure was not performed in patients under 40 years of age. Based on the analysed literature, it was found that if the CA 125 concentration in the blood serum of patients with mucosal tumours exceeded 40 U/mL, laparoscopy was not performed and the patients were treated using an open approach. Conclusions GBOTs are rare neoplasms that require meticulous management to prevent high-risk operative complications. Despite the diagnostic and therapeutic challenges posed by the large size and potential complications of these tumours, with proper medical care, patients can achieve successful outcomes and a good prognosis.

Introduction Advance care planning is a critical process that brings patients, their families, and healthcare providers together to set goals and outline preferences for future medical treatments, especially when chronic or terminal illnesses are involved. Recently, artificial intelligence has begun playing a key role in shared decision making, offering personalized recommendations based on detailed data analysis to help refine treatment decisions. Objective This review explores Artificial Intelligence’s role in shared decision making, noting its potential to enhance treatment precision, reduce the workload for healthcare providers, and empower patients to engage more actively in their cares. Methods The systematic review was conducted using the The Preferred Reporting Items for a Systematic Review and Meta-Analysis Statement 2020 guidelines to ensure a comprehensive and transparent approach. We utilized the online tool Rayyan for screening and selection of relevant studies. Results The review highlights the importance of transparency and clinician involvement to ensure that artificial intelligence remains a supportive, rather than dominant, element in patient care. Emphasizing the human aspect of decision-making is essential, as is fostering a collaborative approach between artificial intelligence and healthcare professionals. Conclusion Artificial intelligence holds promise in transforming shared decision making, ongoing research must address these implementation challenges to secure its ethical and patient-centered use in healthcare.

Background and objective The World Health Organization (WHO) appeal of January 15, 2024, stated “The current number, size and concurrence of multiple outbreaks, the spread to areas free of cholera for decades and alarmingly high mortality rates present a major threat to global health security.” The current state is extremely worrying, considering the difficulties of countries in dealing with cholera epidemics due to the lack of funding and the difficulty in oral cholera vaccine production and administration. This study aims to analyse the past and current influence of anthropization on cholera onset. Methods We analysed the literature, particularly of the last 5 years, on the influence of human actions that impact the spread of cholera. Results The epidemiological data published by WHO and the available literature highlight a strong impact of human actions on the epidemic spread of cholera, the government’s difficulty in making decisions on epidemic prevention or containment, and the fear of the population. Conclusions Cholera should be considered an anthropogenic disaster, considering the historical health analysis of the cholera epidemics in Italy in the last two centuries and in southern Italy and in Naples in 1973.

Objective This study aimed to review the rates of physical frailty and sarcopenia, as well as associated risk factors, among adults aged 60 and older living in the community. Methods A systematic literature search was conducted in PubMed, Wiley Library, Embase, Web of Science, and Cochrane Library for articles published from January 2000 to December 2024. The review followed PRISMA guidelines for meta-analysis. Results Sixteen studies with 41,765 participants were included in the meta-analysis. The pooled prevalence of frailty/sarcopenia was 27% (95% CI: 19–35%). Specifically, the pooled prevalence of frailty was 25% (95% CI: 16–38%) and that of sarcopenia was 23% (95% CI: 13–37%). Age, malnutrition, depression, falls, and hypertension were identified as significant risk factors for frailty/sarcopenia. Conclusion Nearly 30% of older adults in the community are affected by frailty/sarcopenia. Early identification of these risk factors is crucial for the prevention and management of frailty/sarcopenia. Further research is needed to determine effective interventions and strategies to reduce the incidence of frailty/sarcopenia.

Background Infertility is a multifactorial condition that affects both men and women and is influenced by various factors, including overweight and obesity. These conditions, especially in women with polycystic ovary syndrome (PCOS), are strongly associated with hormonal and metabolic imbalances that can impair fertility. Targeted nutritional interventions, such as nutraceutical supplementation, may offer support in improving reproductive outcomes. Methods A narrative review was conducted using PubMed, focusing on publications from the past 12 years with the keywords “nutraceutical,” “overweight,” and “infertility.” The review aimed to identify the main nutraceuticals used in managing infertility and to highlight the importance of a personalized approach tailored to individual patient characteristics. Results Nutraceuticals may represent a safe and cost-effective adjunctive strategy to support fertility in overweight patients, particularly in those with PCOS. Evidence suggests that their effectiveness increases when integrated into a personalized treatment plan based on individual needs and clinical profiles. Conclusions This review offers an updated overview of nutraceutical use in overweight individuals with infertility, outlining both benefits and limitations. It also addresses the often-overlooked medico-legal aspects of prescribing nutraceuticals, emphasizing the need for ethical and legal awareness when incorporating these interventions into clinical practice.

Background Vitamin C is a key to many important functions. It stimulates the immune system by protecting humans from infections and shows notable anti-viral and anti-inflammatory properties. With the antioxidative properties it acts against free radicals and cellular aging and prevents tumors. It is also involved in the synthesis of collagen, a structural protein that is essential for the formation of connective tissue as epidermis, muscle, bone, cartilage, etc. Vitamin C promotes the absorption of iron contributing to the production of red blood cells and the synthesis of hemoglobin. Scurvy is a nutritional disorder caused by low vitamin C levels which manifests with varied symptoms affecting multiple organ systems. Vitamin C also known as l -ascorbic acid, is a water-soluble nutrient and is a necessary element as the humans are unable to synthesize it. Vitamin C has an important role in the biochemical reactions of connective tissue synthesis. Presenting manifestations include malaise, gingival bleeding, impaired wound healing, perifollicular hemorrhage, dry hair and brittle nails, iron deficiency, muscle and joint pain, pulmonary hypertension, and other symptoms. The persistent reduced supply of vitamin C in the absence of treatment is cause of a severe progressive worsening of the clinical conditions. The disorder is uncommonly reported in high social level countries and in mentally wellbeing children. Methods Herewith, we report case-series of eight children with scurvy diagnosed in two Pediatric Hospitals in Catania, Italy “Policlinico G. Rodolico” and “Cannizzaro” in the last 2 years, October 2021–October 2023. In addition, a systematic literature review of 126 articles with 253 cases of scurvy including age, sex, main clinical manifestations, and eventual presence of neurodevelopmental disorders is reported. Main characteristic of vitamin C and negative effects of its lack with clinical manifestations, diagnosis, treatment, and prognosis are also referred. Results Malnutrition, gastrointestinal, and neurological disorders, are the associated predisposing factors. In the present case-series, to the higher incidence of scurvy compared to others Italian Regions may have contributed an erroneous old prejudice of parents who refuse to give citrus fruits to young children as lemon and oranges may cause cystitis as well severe toxicity when mixed with milk. Conclusion This study aims to alert on the scurvy as a possible cause of childhood disorder also in well industrialized regions, and to offer diagnostic tools for identifying subjects suffering from this illness.

Background Although deep brain stimulation (DBS) has been proven to enhance motor function in Parkinson’s disease (PD) patients, its potential adverse impact on cognitive function remains ambiguous. This study aimed to explore the effects of DBS on cognitive function in patients with advanced PD. Methods PubMed, EBSCO, Cochrane Library, Web of Science, and Embase were searched for randomized controlled trials (RCTs) and cohort studies on DBS and advanced PD from inception to January 2025. The main cognitive function assessment tools include but are not limited to Mini-MENTAL State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Results A total of 7 RCTs and 11 cohort studies were included. Analyses reveals no significant differences in MMSE (mean difference [MD] = −0.33, P = 0.19) and MDRS (MD = −0.75, P = 0.08) between the DBS group and the best medical therapy (BMT) group overall. However, the DBS group had significantly worse cognitive function after treatment than the BMT group in phonemic fluency (MD = −3.17, P = 0.03). No significant differences were observed between the groups in other domains, including information processing, memory, executive function, and visuospatial function. Conclusions DBS poses a potential risk to cognitive function in patients with advanced PD.

Sepsis is an inflammatory disease caused by a severe infection, and its pathological process involves complex immune reactions and inflammatory cascades. This condition often leads to multiple organ dysfunction syndrome, which is one of the main causes of patient mortality. In recent years, researchers have paid extensive attention to the protective role of selenium (Se) in sepsis. Se is believed to potentially counteract organ dysfunction caused by sepsis through various mechanisms and is considered a potential therapeutic strategy. This review extensively discusses the potential mechanisms of Se in sepsis. We explore the antioxidant and anti-inflammatory properties of Se, as well as its regulatory effects on immune cell activity, expression of inflammatory mediators, and oxidative stress. In addition, we examine the impact of Se on organ damage and organ dysfunction caused by sepsis, with a focus on its protective effects on important organs such as the cardiovascular system, respiratory system, kidneys, and liver. We evaluate relevant preclinical and clinical studies to assess the potential of Se as a treatment for sepsis-related organ dysfunction. We discuss the optimization of Se administration routes, dosages, and timing, and summarize the impact of Se on clinical outcomes and survival rates. In summary, Se demonstrates significant potential as a therapeutic strategy in sepsis-related organ dysfunction. However, further research is still needed to delve into the mechanisms of Se and optimize its application in clinical practice. This will provide breakthroughs in the treatment of sepsis patients, improving their prognosis and survival rates.

Background Hyperkalemia is a potentially life-threatening electrolyte disorder, especially in patients with chronic kidney disease and those undergoing dialysis. Its management is complex due to the need to balance potassium control with overall patient stability. Objectives The aim of this systematic review is to evaluate current therapeutic strategies for hyperkalemia in dialysis patients, including diuretics, ion-exchange resins, and newer agents such as sodium zirconium cyclosilicate (SZC). Methods A systematic search was conducted in Scopus and Web of Science, applying filters for language, recency (≤5 years), and journal quality. After removing duplicates and irrelevant records, 11 high-quality studies were included. Results New therapies like SZC and patiromer demonstrated efficacy in maintaining safe potassium levels. The potassium binding pack showed promise in acute and resource-limited settings. Evidence challenges strict dietary potassium restrictions, especially regarding plant-based foods, and highlights the importance of individualized nutritional plans. Continuous potassium monitoring is essential to preserve residual kidney function. Conclusion Hyperkalemia management in dialysis patients benefits from an integrated approach combining pharmacologic treatment, tailored nutrition, and close monitoring. Novel interventions and evolving dietary guidelines may improve safety, effectiveness, and quality of life in this vulnerable population.

Background information Delayed graft function (DGF), defined as the need for dialysis within the first week of a kidney transplant, is a common complication, particularly in extended criteria donor transplants, where its incidence ranges from 21 to 31%. Objectives We observed a prolonged case of DGF in a 47-year-old patient with chronic kidney disease (CKD) resulting from diabetic nephropathy. The patient, classified in a moderate immunologic mismatch group, received a marginal deceased donor kidney. Results For the first 4 weeks post-transplantation, graft function was impaired. After 29 days of anuria, the transplanted kidney began to recover. The literature review found few clinical cases of DGF extending beyond 1 month. Our patient had several risk factors for DGF, including diabetes mellitus, pre-transplant hemodialysis, and moderate immunologic mismatch. Additionally, the marginal graft increased the risk of ischemia-reperfusion injury and glycocalyx damage. However, it remains unclear how these factors influenced the duration of DGF. The exact cause of the extended DGF in this case remains unknown. Although the literature identifies key risk factors for DGF, data on factors leading to prolonged kidney dysfunction are lacking. Therefore, decisions to remove a non-functioning transplanted kidney should not be made hastily.

Background Comorbid type 2 diabetes mellitus (T2DM), severe obesity, and chronic myeloid leukemia (CML) present therapeutic challenges, especially given the limited data on glucagon-like peptide-1 (GLP-1) receptor agonists in this setting. Methods We describe a 33-year-old female with poorly controlled T2DM (HbA1c 10.7%), severe obesity (BMI 47.05 kg/m 2 ), and stable CML on tyrosine kinase inhibitor therapy. She received once-weekly semaglutide (0.5–1.5 mg) for 6 months, alongside insulin glargine and dapagliflozin/metformin. Clinical, biochemical, and molecular parameters were monitored. Results After 6 months, her HbA1c declined from 10.7 to 5.5%, fasting plasma glucose from 16.2 to 5.3 mmol/L, and body weight decreased by 18 kg. Lipid parameters improved, and molecular analysis confirmed continued CML remission (undetectable BCR-ABL1). The patient experienced only mild, transient gastrointestinal side effects. Conclusion In this complex case, semaglutide proved safe and effective for achieving glycemic control and weight reduction without compromising CML stability. These findings suggest that GLP-1 receptor agonists may be a viable therapeutic option for patients with coexisting T2DM, severe obesity, and stable CML, warranting further investigation in broader populations.

Glycogen storage disease type IIIa (GSD IIIa) is a rare etiology among patients with adult-onset myopathy, which is typically associated with axonopathy rather than demyelination. We report a genetically and pathologically confirmed case that exhibited prominent electrophysiological hallmarks of demyelination, including prolonged distal motor latency, temporal dispersion, prolonged F-waves, and conduction block. The presence of these diverse demyelinating characteristics in this context, excluding other factors, is infrequently reported, suggesting that glycogen accumulation may influence not only muscles but also potentially the myelin, thereby broadening our comprehension of this rare disease spectrum.

Introduction Cardiac hemangiomas are slow-growing benign tumours of the heart. Patients may be asymptomatic or present a multitude of signs or symptoms. Methods We report herein the case of a 72-year-old woman with a giant right atrial mass. The patient suffers from abdominal swelling related to ascites. The histological examination of the tranjugular biopsy suspected an atrial myxoma. Results The patient was scheduled for surgical excision of the cardiac tumour. Radical resection of a 13 cm mass was performed. The histological diagnosis revealed cardiac hemangioma. Conclusion Cardiac hemangiomas can rarely grow larger than 5 cm, cause few symptoms, and are easily confused with atrial myxomas. Hepatomegaly and ascites may be signs of cardiac hemangioma.

Granular cell tumors (GCTs) are rare, benign tumors typically originating from Schwann cells, with the head and neck being the most common sites. Laryngeal GCTs, particularly those affecting the vocal cords, are exceedingly rare in adults. This report presents a 28-year-old female with a GCT of the left vocal cord extending into the subglottic region. The patient presented with progressive dysphonia, and laryngoscopy revealed a 2 cm × 1 cm mass on the left vocal cord. Microlaryngeal examination confirmed subglottic extension, and the tumor was excised using carbon dioxide (CO 2 ) laser. Histopathological analysis confirmed GCT with S100 positivity. Two months later, the patient developed a late complication – granuloma formation at the excision site – necessitating revision surgery. The patient was symptom-free at the 12-month follow-up. GCTs in the vocal cords with subglottic extension are rare and challenging to diagnose and treat. They are generally benign lesions and rarely undergo malignant transformation. Diagnosis is confirmed through histology, and treatment involves wide local excision, with re-excision needed for recurrence. GCTs are chemo- and radio-insensitive, making surgery the primary treatment. This case underscores the importance of accurate diagnosis and tailored treatment, highlighting the need for further research on this rare condition.

Scleroderma is an autoimmune disorder characterized by vasculopathy, progressive skin fibrosis, and dysfunction of internal organs. Esophageal involvement is seen in most scleroderma patients. There is no specific treatment for dysphagia caused by scleroderma. FLIP technology is a novel diagnostic and therapeutic modality to assess the tightness of esophageal sphincters and esophageal motility and also provide therapeutic dilation. We describe the case of a patient with scleroderma who presented with dysphagia. Upper endoscopy was unremarkable. Esophageal manometry revealed aperistalsis with normal upper and lower esophageal sphincter (LES) relaxation. Barium esophagram demonstrated poor esophageal motility and hold-up of the barium tablet at the gastroesophageal junction. EndoFLIP test during sedated upper endoscopy revealed normal LES distensibility and absent peristalsis of the esophageal body. Due to dysphagia, the LES was dilated with a 30 mm EsoFLIP. A barium esophagram following the dilation revealed a significant reduction in esophageal body diameter, normalization of barium tablet transit, and symptomatic improvement in dysphagia. Our case is the first report of the use of EsoFLIP to help improve dysphagia in a scleroderma patient. It illustrates the importance of multi-modal functional testing in patients with dysphagia and suggests the utility of EsoFLIP in the treatment of dysphagia in these patients.

Objectives Acute ischemic stroke caused by internal carotid artery (ICA) occlusion carries high risks of disability and death. While treatments such as thrombolysis, mechanical thrombectomy, and revascularization offer benefits, many patients experience limited recovery. Molecular hydrogen, with its antioxidant and anti-inflammatory properties, shows promise as a neuroprotective agent. This case report explores the adjunctive use of molecular hydrogen–rhodiola therapy in a patient with ICA occlusion, with a focus on immune modulation and clinical outcomes. Case presentation A 68-year-old male with a history of paroxysmal atrial fibrillation presented with left-sided hemiplegia and was diagnosed with right ICA occlusion (NIH Stroke Scale: 12; modified Rankin Scale: 5). Endovascular thrombectomy was attempted but unsuccessful (modified Thrombolysis in Cerebral Infarction score = 0). The patient subsequently underwent superficial temporal artery to middle cerebral artery bypass surgery. Postoperatively, he was initiated on daily molecular hydrogen-rhodiola capsule therapy. Serial immunological assessments demonstrated a progressive increase in type 1 regulatory T (Tr1) cells and regulatory B cells, along with enhanced T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) expression on cytotoxic T (Tc) cells. Clinically, the patient exhibited marked neurological recovery, with motor strength improving from Medical Research Council grade 1 to grade 5 in the affected limbs over six months. Notably, steroid therapy was discontinued without relapse, and no adverse events were observed. Conclusion This case highlights the potential of molecular hydrogen-rhodiola therapy as a safe and effective adjunctive treatment for ischemic stroke due to ICA occlusion. Notable improvements in immune modulation and motor function support its possible role in neurovascular recovery.

Background Any variance of the normal coronary vasculature is regarded as a coronary artery anomaly (CAA). An atypical left coronary artery arising from the right aortic sinus of Valsalva has been identified as the rarest CAA and the second leading cause of sudden cardiac death (SCD) in young people. Prompt identification of the anomalous vessel is essential to mitigate early mortality risk. Case summary A 33-year-old male, ex-smoker presented with exertional breathlessness and retrosternal chest tightness for the past 1 year. Past history also revealed a significant decline in his exercise tolerance. His initial work-up, which included a resting electrocardiogram and echocardiogram were within normal limits. His exercise tolerance test however, was discontinued early due to the onset of symptoms, and his exercise stress echocardiogram proved positive for angina at a low workload. The cardiac computed tomography angiography revealed a common origin for the left and right coronary systems from the right ostium, with the left main stem following an inter-arterial course and showing mild, diffuse narrowing. The patient was green-lit for coronary artery bypass grafting (CABG). Post recovery and almost 2 years on, he has remained symptom-free and has regained his physical activity. Conclusion This case underlines the need for prompt identification and subsequent management of anomalous coronary arteries, given their association with SCD. Timely surgical intervention such as CABG can greatly mitigate the risk of grievous complications. The patient’s complication-free postop recovery and resumption of physical activity, assures the reader that it is a viable and durable option with long-term quality of life improvement.

Background Rapid application of transcatheter valve replacement for valve diseases has promoted the development of biological valves. Different efforts have been made to improve the surface properties of valves. We developed a new method using arginine-glycine-aspartate (RGD) peptide and epoxy chloropropane (EC). Our goal was to evaluate and detect the surface biological characteristics of valve materials using RGD and EC treatments. Methods The surfaces of the valve materials used in the GA-EC and RGD-EC groups were smooth and relatively dense, as observed using a scanning electron microscope. Results More MSCs adhered to and grew on the samples in the GA-EC and RGD-EC groups than in the GA group. The apoptosis rate of MSCs was markedly decreased, whereas the expression of vimentin was elevated in the GA-EC and RGD-EC groups ( P < 0.05). The adherent ability of MSCs in the RGD-EC and GA-EC groups was significantly higher than that in the GA group ( P < 0.05). Conclusions The new treatment method using RGD and EC improves the biological properties of the surface of the biological valve materials.

Background Flavanols (FLs), a group of polyphenols abundant in cocoa and red wine, have been associated with improved cognitive function, particularly hippocampus-dependent memory in older adults. However, their poor bioavailability has limited understanding of the mechanisms underlying their effects on the brain. This study aimed to investigate the cognitive and molecular responses following acute FLs administration in mice. Methods Male C57BL/6J mice were orally administered FLs (25 mg/kg) or distilled water (DW) and subjected to a novel object recognition test. In one experiment, FLs were administered before training, in another, after training. Exploratory behavior and the discrimination index (DI) were analyzed. Hippocampal tissues were collected at 15 min to 4 h post-administration to assess levels of brain-derived neurotrophic factor (BDNF) and phosphorylated extracellular signal-regulated kinase, cAMP response element-binding protein (CREB), and tyrosine kinase receptor type 2 by western blotting. Results Mice treated with FLs before training exhibited significantly longer exploration of the novel object and higher DI, whereas no enhancement was observed when FLs were administered after training. CREB phosphorylation increased at 30 min post-administration, and BDNF levels were elevated at 2 and 4 h. Conclusion These findings suggest that FLs enhance short-term memory via hippocampal CREB activation and BDNF upregulation. Despite low systemic absorption, the rapid effects observed may involve sensory signaling pathways, potentially triggered by the astringent properties of FLs. This study provides mechanistic insight into the cognitive benefits of dietary FLs.

Primary chemoresistance to platinum-based treatment is observed in approximately 33% of individuals diagnosed with ovarian cancer; however, conventional clinical markers exhibit limited predictive value for chemoresistance. This study aimed to discover new genetic markers that can predict primary resistance to platinum-based chemotherapy. Through the analysis of three GEO datasets (GSE114206, GSE51373, and GSE63885) utilizing bioinformatics methodologies, we identified two specific genes, MFAP4 and EFEMP1. The findings revealed that the areas under the receiver operating characteristic curves for MFAP4 and EFEMP1 were 0.716 and 0.657 in the training cohort, and 0.629 and 0.746 in the testing cohort, respectively. In all cases or in cases treated with platin, high expression of MFAP4 and EFEMP1 was linked to shortened overall survival and progression-free survival. MFAP4 and EFEMP1 were positively correlated with epithelial–mesenchymal transition, TGF-β signaling, KRAS signaling, and so on. The high expression groups of MFAP4 and EFEMP1 exhibited elevated stromal, immune, and ESTIMATE scores. Finally, we constructed a regulatory network involving lncRNA–miRNA–mRNA interactions. In summary, MFAP4 and EFEMP1 have the potential to serve as predictive indicators for both response to platinum-based chemotherapy and survival rates, and might be regarded as innovative biomarkers and therapeutic targets for OC patients.