Volume 21, Issue 1

Objectives To explore the effects of curcumol on ferroptosis and angiogenesis of hepatic sinusoidal endothelial cells, further elucidate the molecular mechanism of curcumol against liver fibrosis, and provide new ideas for the prevention and treatment of chronic liver disease. Methods We used VEGF to construct pathological model group, and divided hepatic sinusoidal endothelial cells into blank group, model group, high, middle and low curcumol group. Ferroptosis and angiogenesis were detected by various cell molecular biology experiments. Results Curcumol significantly inhibited the proliferation and migration of hepatic sinusoidal endothelial cells, significantly increased the expression of P53 and TFR1 protein, significantly decreased the expression of FTH1 protein, significantly promoted the occurrence of iron death, and significantly inhibited angiogenesis. When we knocked out p53, the effect of curcumol contributing to the onset of ferroptosis was rescued, while curcumol’s role in inhibiting angiogenesis was saved, which was the same effect as when we used Ferrostatin-1. Conclusions Curcumol targets the P53-TFR1-FTH1 signalling axis and induces massive deposition of iron ions in hepatic sinusoidal endothelial cells, leading to the onset of ferroptosis inhibiting hepatic angiogenesis, which may be one of the molecular mechanisms of its anti-hepatic fibrosis.

Objectives To explore the optimal initiation time of hyperbaric oxygen therapy (HBOT) for moderate-to-severe acute carbon monoxide poisoning (ACOP) and to assess the prognostic value of lactate clearance and early MRI findings. Methods This single-center retrospective study included 12 ACOP patients (2020–2023) treated with HBOT within 6 h after admission. Patients were categorized by HBOT initiation time: early (≤3 h, n=8) and delayed (>3 h, n=4). Clinical, biochemical, and imaging data were analyzed. Primary outcomes were time to regain consciousness and Barthel Index at 6 months. Results Median HBOT initiation was 112 min. Early treatment was associated with faster organ function recovery (greater SOFA score reduction, p<0.05). Lactate normalized within a median of 17.5 h, and clearance >50 % in 24 h correlated with better neurological outcomes (p=0.002). MRI detected early globus pallidus injury more sensitively than CT. At 6 months, 83.3 % recovered functionally; one developed delayed encephalopathy. Conclusions Early HBOT initiation (≤3 h) may facilitate metabolic and neurological recovery in ACOP. Early lactate clearance and MRI findings may serve as prognostic markers. Given the small sample size and absence of a non-HBOT control group, these results are exploratory and require confirmation in larger studies.

Objectives The present study focused on exploring the role of orosomucoid 1 (ORM1) in rheumatoid arthritis (RA). Methods Differentially expressed genes in GSE15573 dataset were analyzed by bioinformatics. Fibroblast-like synoviocytes (FLS) from RA patients were stimulated with collagen-II, followed by quantification of ORM1 and C-C chemokine receptor 5 (CCR5) expressions. The interaction between ORM1 and CCR5 in FLS was examined by Co-immunoprecipitation. After ORM1 intervention or maraviroc treatment, the effect of ORM1 or CCR5 as well as their interplay in the stimulated cells was investigated using molecular experiments, methylthiazolyldiphenyl-tetrazolium bromide assay and transwell assay. Rats underwent collagen-induced arthritis (CIA) modeling. Arthritis index scoring, western blot assay and histopathological evaluation were performed in CIA rats with ORM1 or CCR5 knockdown. Results ORM1 and CCR5 were highly expressed in collagen type II (CII)-stimulated FLS and synovial tissues of CIA rats. The expression of CCR5 was positively regulated by ORM1, and the interaction of ORM1 and CCR5 was confirmed. CII stimulation enhanced viability, migration and invasion of FLS, but these effects were antagonized in the absence of ORM1 or CCR5. Knockdown of ORM1 or CCR5 in CIA rats reduced arthritis index, while alleviating cartilage erosion, inflammatory infiltration and synovial hyperplasia of ankle joints. Conclusions ORM1 deficiency suppresses the aggressive phenotype of FLS to reduce RA progression by downregulating CCR5.

Objectives To identify causal genes for benign prostatic hyperplasia (BPH) based on single-cell RNA sequencing (scRNA-seq) and genome-wide association studies. Methods We explored scRNA-seq datasets to identify the differentially expressed genes (DEGs) in BPH patients vs. healthy controls. Mendelian randomization (MR) was conducted to investigate the causal relationships between the identified DEGs and BPH. Bayesian colocalization and reverse MR were performed to consolidate the MR findings. Potential therapeutic drugs targeting causal genes were explored via molecular docking. The results of bioinformatics analyses were validated through experiments including flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence staining. Results BPH patients showed an increased proportion of myeloid cells in the prostate transition zone, with 85 classical monocyte-specific DEGs. Among these, SLC25A37 was causally associated with BPH based on MR, Bayesian colocalization, and reverse MR analyses. Functional analyses indicated its involvement in proliferation-related signaling pathways in classical monocytes. Ferriheme chloride and catechol were identified as potential drugs targeting SLC25A37. In vitro study confirmed increased expression levels of SLC25A37 and myeloid cells in BPH tissues. Conclusions Our integrative analyses revealed SLC25A37 as a novel causal gene in BPH pathogenesis, unveiling potential therapeutic strategies for BPH treatment.

Objectives Stroke is a major cause of long-term disability and cognitive impairment, substantially affecting patients’ quality of life and functional independence. Effective strategies for post-stroke cognitive recovery remain limited. To evaluate the effects of transcranial magnetic stimulation (TMS) combined with reminiscence therapy on cognitive function and functional independence in stroke patients. Methods A retrospective cohort study was conducted at a rehabilitation hospital from March 2017 to October 2024, including patients with ischemic stroke and cognitive impairment who received either routine treatment (n=68) or TMS combined with reminiscence therapy (n=66). Cognitive and functional outcomes were assessed using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), and Functional Independence Measure (FIM). Results Post-treatment, the TMS plus reminiscence therapy group showed significantly higher MMSE (27.42 ± 3.08 vs. 25.18 ± 3.41, p=0.0001) and MoCA scores (20.05 ± 3.99 vs. 18.44 ± 4.05, p=0.0020), and shorter TMT times (65.28 ± 9.75 vs. 72.45 ± 10.32, p<0.001). FIM scores were also higher (92.18 ± 7.06 vs. 88.35 ± 7.15, p=0.0024). No significant differences in adverse events were observed. Conclusions TMS combined with reminiscence therapy may effectively enhance cognitive function and functional independence in patients with post-stroke cognitive impairment.

Objectives High altitude poses extreme living environment for humans, impacting human physiology and leading to physiological adaptations, including higher hemoglobin levels in highlanders. However, further understanding is required regarding the medical reference ranges at very high altitudes (>4,500 m). Therefore, we conducted a study involving 1,656 healthy individuals from the “Health Improvement at Very High Altitude (HI-VHA)” population to establish a reference range for 25 biochemical analyses in this population residing at very high altitudes. Methods The HI-VHA project sampled 3,564 individuals from Tibet Autonomous Region above 4,500 m. After strict exclusion criteria, 1,656 healthy individuals were included to establish age and sex stratified reference intervals (RIs) for 25 biochemical analytes using serum samples. Results RIs were generated following the statistical guidelines outlined in CLSI C28-A3. Among the 25 biochemical analytes studied, the levels of ALT, GLB, CREA, UA, HDLC, and HCY showed significant variations by gender, while ALB, AG, CHOL, and DBIL were influenced by age. LDLC was the only analyte affected by both gender and age. AST, TP, TBIL, IBIL, Glu, TG, LDLC, CRP, K, Na, Cl, Ca, Mg, and P, comprising 14 analytes, were not influenced by gender or age. Conclusions We established the RIs for 25 biochemical analytes in the very high-altitude population. These RIs are crucial for disease diagnosis and health management of individuals living at very high altitudes. Moreover, an accurate identification of diseases commonly observed at very high altitudes provides insights into the biological adaptation mechanisms of humans residing in such environments.

Objectives Deep vein thrombosis (DVT) demonstrated significant health risk in elderly populations, with numerous comorbidities and biomarkers affecting its incidence. This study evaluated the prevalence, potential allied risk factors for DVT in elderly. Methods A literature search was conducted across PubMed, Science Direct, Cochrane Library, and Google Scholar. After excluding studies, 26 studies were comprised in the study. Data were collected for DVT prevalence and associated risk factors. Results A total of 11,651 participants comprised from China, Japan, Germany, Saudi Arabia, and Thailand. The overall DVT prevalence was 17.10 %, with higher prevalence in females (67.08 %) than males (32.92 %). Age was significantly associated with increased DVT risk (OR=1.54, 95 % CI: 0.34–2.73, p<0.01). While DVT incidence was insignificantly higher among hypertensive and diabetic patients. Significant associations identified between DVT occurrence and malignancy (OR=1.36, 95 % CI: 1.02–1.83, p<0.04), as well as recent surgical history (OR=1.34, 95 % CI: 1.01–1.77, p<0.04). Elevated D-dimer were strongly linked to DVT risk (OR=1.13, 95 % CI: 1.08–1.17, p<0.001). Conclusions This review suggested the significant impact of aging, malignancy, recent surgery, and elevated D-dimer levels on DVT risk in elderly and recommends the assessment of clinical signs, risk factors, and biomarkers in elderly individuals.

Objectives To evaluate the long-term regulatory effects of high-fiber low-fat (HFLF) diet on gut microbiota diversity and inflammation/barrier-related markers in DSS-induced recurrent colitis mice. Methods A recurrent DSS model was established through multiple cycles of DSS administration. Mice were randomly assigned to HFLF diet vs. control/standard chow ± positive control groups. Multi-timepoint sampling was conducted throughout the study. 16S rRNA sequencing, SCFA quantification, and qPCR/ELISA/immunohistochemistry/Western blot analyses were performed. Results HFLF diet significantly improved clinical phenotype, increased gut microbiota diversity, promoted beneficial bacterial genera, enhanced SCFA production, and modulated inflammation/barrier indicators throughout the recurrence-remission cycles. Conclusions HFLF diet provides sustained protection during recurrence-remission processes through microbiota-SCFA-inflammation axis modulation, offering potential translational applications for IBD management.

Objectives Infective endocarditis (IE) is a life-threatening infection of the inner lining of the heart resulting in severe complications such as valvular destruction and systemic embolism. Surgical intervention is often required to manage advanced cases. This study describes the clinical, paraclinical, and microbiological characteristics of patients with IE undergoing valve surgery at a tertiary cardiovascular centre in a developing country. Methods This retrospective study analysed 176 patients with IE who underwent valve surgery at a single centre in Vietnam between January 2019 and December 2023. Results The mean age of the cohort was 43.6 ± 15.9 years, with 62.5 % male patients and 13.5 % having a history of cardiac surgery. Mitral valve involvement was the most common lesion (94.9 %), predominantly presenting as regurgitation (96.4 %). The mean white blood cell count was 10.3 ± 8.6 K/μL, indicating an inflammatory response. Blood cultures were positive in 67.5 % of cases, with Viridans streptococci (34.6 %) and Streptococcus spp. (34.6 %) being the most frequently identified pathogens. Conclusions This study provides comprehensive data on patients with IE undergoing surgery in Vietnam, highlighting the importance of early diagnosis, microbiological identification, and surgical intervention for improving patient outcomes in resource-limited settings.

Objectives Delirium is a frequent complication in elderly and critically ill patients, associated with significant morbidity and mortality, prolonged hospitalization, increased healthcare costs, and long-term cognitive impairment, emphasizing the need for early identification and prevention strategies. In this study, we aimed to assess the association between pregabalin use and the risk of delirium in elderly intensive care unit (ICU) patients. Methods This retrospective cohort study analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) was applied to control for baseline confounders. Multivariate logistic regression, inverse probability of treatment weighting (IPTW), and subgroup analyses were conducted to validate the findings. Results Out of 12,327 patients, 309 pregabalin users were matched with 1,236 non-users through 1:4 PSM. Pregabalin use was significantly associated with increased delirium risk in patients aged 60 and older, with odds ratios (ORs) of 1.72 (1.31–2.25), 1.90 (1.44–2.49), 1.89 (1.37–2.58), and 1.91 (1.58–2.31) across models. Subgroup analyses confirmed this association across most variables. Notably, the risk was significantly higher among patients not receiving analgesia (p for interaction <0.05). Conclusions Pregabalin use is associated with an elevated risk of delirium in critically ill patients aged 60 and above. These findings have important implications for medication management and delirium prevention in the ICU.

Objectives Neonatal infections, which continue to be a major cause of morbidity and mortality globally, can be avoided with proper umbilical cord care. There is still no widely recognized standard for cord care despite numerous antiseptic techniques, and the hunt for safe, natural, and efficient substitutes is becoming necessary. In this regard, OZOILE, a formulation based on stable ozonides with wound-healing and antibacterial qualities, may be a viable choice. The purpose of this study was to retrospectively assess the impact of topical OZOILE on the timing of umbilical cord detachment and the avoidance or reduction of infection-related problems in newborns. Methods The study was conducted in the Complex Operational Unit of Neonatology and Neonatal Intensive Care of the “Annunziata” Hospital-Cosenza (Italy) and included healthy newborns with a gestational age from the 35th to the 41st weeks of gestation, born to mothers with age ranging from 18 to 40 years. Results Daily application of OZOILE spray oil, directly to the umbilical cord 3 times a day was able the stump fell off in a short time from 5 to 7 days and without any complications. OZOILE reduces secondary alterations of falling umbilical stump. Conclusions In conclusion, OZOILE intervention could be a good candidate for umbilical cord care.

Objectives This study aimed to evaluate the significance of integrating hearing screening with genetic testing for hereditary deafness. Methods A retrospective analysis was performed on the hearing screening and genetic testing outcomes of 10,754 newborns delivered at Hangzhou Women’s Hospital from June 2020 to December 2022. Hearing evaluations were conducted using transiently evoked otoacoustic emissions (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected, and 15 variants across four genes (GJB2, GJB3, SLC26A4, and mtDNA 12S rRNA) were examined using a DNA microarray platform. Results Among the 10,754 infants, the most commonly detected mutations were GJB2c.235delC (47.26 %) and SLC26A4 IVS7-2 A>G (21.17 %). A total of 62 infants (0.58 %) were referred for additional hearing assessments, while 529 (4.92 %) tested positive for genetic mutations (including heterozygous, homozygous, or compound heterozygous variants, as well as mtDNA 12S rRNA homoplasmy), with 522 (4.85 %) passing the hearing screening. Three infants (0.028 %) had two variants in GJB2 (either homozygous or compound heterozygous), and one of these infants passed the newborn hearing test. Additionally, 33 infants (0.307 %) had the MT-RNR1 variant (m.1555A>G or m.1494C>T), all of whom passed the hearing screening. Conclusions The most prevalent mutations associated with deafness were identified as GJB2 c.235delC, SLC26A4 IVS7-2 A>G, and m.1555A>G. The combination of hearing screening and genetic testing for deafness effectively identifies high-risk children with hereditary deafness for further intervention.

Objectives To investigate the relationship between serum miR-342, miR-148a, and acute lung injury (ALI) in sepsis patients. Methods A total of 177 sepsis patients were divided into ALI and non-ALI groups; ALI patients were further classified as mild, moderate, or severe. 162 pneumonia patients served as controls. Serum miR-342 and miR-148a levels were measured using RT-qPCR. Results Sepsis patients had lower miR-342 and higher miR-148a than controls (p<0.05). Compared with non-ALI patients, the ALI group showed higher miR-148a, PaCO2, APACHE II scores, and RI, but lower miR-342 and OI (p<0.05). miR-342 decreased and miR-148a increased with ALI severity. Correlation analysis revealed that miR-342 was negatively correlated with PaCO2, APACHE II, and RI, and positively with OI, while miR-148a showed opposite trends. The AUC for predicting ALI using miR-342, miR-148a, and their combination was 0.818, 0.775, and 0.896, respectively. Conclusions Sepsis patients with ALI exhibit low serum miR-342 and high miR-148a, and their combination can effectively predict ALI occurrence.

Objectives This study provides the first comprehensive assessment of the global thyroid cancer burden from 1990 to 2021, focusing on incidence, mortality, and DALYs trends across 204 countries. Methods Using Global Burden of Disease (GBD) 2021 data, age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) were calculated. Associations with the Socio-demographic Index (SDI) were analyzed via linear regression. Results Globally, the age-standardized incidence rate increased from 2.06 to 2.91 per 100,000 (EAPC=1.25), with women accounting for 67 % of cases. Mortality showed a modest decline (EAPC=−0.23), but DALYs remained high (14.57 million in 2021). High-SDI regions, such as North America, accounted for 72 % of cases, reflecting intensive screening, whereas low-SDI regions, particularly Sub-Saharan Africa, contributed 68 % of deaths due to delayed diagnosis. High BMI contributed 1.68 % of DALYs, peaking at 4.26 % in Andean Latin America. Incidence varied significantly across countries, from 7.13 per 100,000 in Saudi Arabia (linked to iodine excess) to 0.014 per 100,000 in Tajikistan (iodine deficiency). Mortality was highest among elderly males, reaching 12.57 per 100,000 in those aged ≥90 years. Conclusions The rising global burden of thyroid cancer highlights pronounced gender and regional disparities. High-SDI regions should prioritize risk-stratified strategies to reduce overdiagnosis, while low-SDI regions require improved access to healthcare. Targeted efforts in early detection and metabolic risk reduction are critical to mitigate disease burden.

Objectives Our research aimed to explore the potential indicators in discriminating mycoplasma pneumoniae pneumonia (MPP) from viral pneumonia (VP) in children. Methods TaqMan PCR testing was used to detect respiratory pathogens in all pneumonia patients. The serum levels of IL-37 and YKL-40 were measured by ELISA. While the expression levels of YKL-40 and IL37 mRNA in PBMCs were detected by qRT-PCR. We calculated the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) values from blood routine test results. This study had been registered in the Chinese Clinical Trials Registry System (MR-32-24-025608). Results 170 patients were selected, including 85 MPP patients and 85 VP patients. In addition, 85 healthy control children were selected for comparison. The levels of serum YKL-40, IL-37 and their mRNA expressions in MPP patients were significantly higher than in VP patients and healthy control. Similarly, MPP patients had the highest levels of NLR and PLR. According to the ROC curve result, the combination of two indicators (YKL-40 and NLR) was the strongest predictor of MP vs. VP. Conclusions These results indicate that YKL-40 and NLR constitute the critical combination of biomarkers useful for differentiating between MPP and VP in children.

Objectives Patients with long-term ulcerative colitis (UC) have a significantly increased risk of colon cancer compared to normal individuals. By analyzing the pathways of ulcerative colitis and colon cancer, we identified a common risk pathway – Vascular Endothelial Growth Factor (VEGF). Methods Based on the Gene Set Variation Analysis (GSVA) scores of the VEGF pathway in colon cancer patients, we divided them into three groups: high, medium, and low. We performed clinical characteristic and immune-related analyses on these three groups, conducted differential gene analysis, performed univariate and multivariate Cox analyses on the differential genes to screen out gene signatures. A risk model was constructed and validated in the UC cohort. Colon cancer patients were classified into high-and low-risk groups based on risk scores, clinical characteristics, immune microenvironment, immunotherapy, and drug sensitivity were analyzed for both groups. Results The high expression group had higher clinical staging and pathologic staging, higher immune microenvironment scores, and greater immune cell content. The risk model we constructed demonstrated good prognostic predictive ability not only for colon cancer but also for UC. The high-risk group had a lower survival rate, while the low-risk group had a better response to immunotherapy. Conclusions These findings provide new insights into the treatment of colon cancer.

Objectives This study aimed to explore the mechanism by which exogenous macrophage migration inhibitory factor (MIF) reduces apoptosis of mouse bone marrow mesenchymal stem cells (BMSCs) induced by irradiation under high oxidative stress. Methods BMSCs were cultured and exposed to irradiation using a linear accelerator to establish a radiation damage model. Cell viability was detected by the CCK-8 assay. Apoptosis rate and intracellular reactive oxygen species (ROS) production were measured by flow cytometry and fluorescence microscopy. The expression levels of Long non-coding RNA (lncRNA) MEG3, NOX4, and apoptosis-related genes were detected by western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence. Results The CCK-8 assay, western blot, and flow cytometry confirmed that irradiation effectively induced BMSCs apoptosis and upregulated the expression of lncRNA MEG3, which was positively correlated with NOX4 expression. Western blot, immunofluorescence, and RT-qPCR results demonstrated that MIF protected BMSCs from irradiation-induced apoptosis and downregulated the expression of MEG3 and NOX4. Furthermore, MEG3 siRNA was shown to reduce irradiation-induced apoptosis. Western blot and flow cytometry analyses revealed that overexpression of either NOX4 or MEG3 could reverse the protective effect of MIF. Conclusions LncRNA MEG3 is an important regulatory factor in irradiation-induced apoptosis. The mechanism by which MIF protects BMSCs from irradiation-induced apoptosis is likely mediated through the regulation of the LncRNA MEG3/NOX4 signaling pathway.

Objectives This study sought to identify the risk factors associated with venous thrombosis for spontaneous intracerebral hemorrhage (ICH) in a long term. Methods A retrospective analysis was performed on the ICH patients between January 2021 and December 2022. Results A total of 737 patients were examined with 86 patients (11.7 %) of venous thrombosis. The risk factors linked to venous thrombosis were the length of hospital stay (p<0.001), admission NIH Stroke Scale (p=0.008), and D-dimer levels (p=0.041). No significant differences in mortality rates existed at any timepoint in this study between patients with and without venous thrombosis after correction analysis (p>0.05). However, patients who developed a venous thrombosis exhibited a higher rate of poor outcomes compared to patients who did not develop a venous thrombosis (p<0.05) at the time of hospital discharge (90.7 % vs. 59.6 %), 90 days post-onset (73.2 % vs. 41.6 %), and 1-year post-onset (73.2 % vs. 41.0 %). Conclusions The identified risk factors for venous thrombosis among ICH patients include extended hospitalization, elevated NIH Stroke Scale score and D-dimer level. The occurrence of a venous thrombosis correlated with inferior functional outcomes at the time of hospital discharge, at 90 days and 1 year after onset.

Objectives The research on idiopathic recurrent pregnancy loss (RPL) mainly focuses on women, but recently researchers began to explore the potential contribution of male partners. Growing evidence suggests that male tuberculosis may contribute to adverse pregnancy outcomes. We studied whether men’s previous tuberculosis may contribute to idiopathic RPL in early pregnancy. Methods A retrospective study on 182 couples with idiopathic RPL in early pregnancy (study group) and 260 couples with fertility (control group) who visited the Fourth Hospital of Hebei Medical University from January 1, 2021 to December 31, 2022 was conducted. Logistic regression analysis was performed to nvestigate the correlation between male partner’s previous pulmonary tuberculosis and idiopathic RPL. Results Male partners accounted for 37.91 % of previous pulmonary tuberculosis in the study group, and the sperm DNA fragmentation index (DFI) in the study group was higher than that in the control group (17.52 ± 7.87 vs. 7.79 ± 4.49, p=0.000). After adjusting for factors, Logistic regression analysis showed that male partners with previous tuberculosis history were prone to RPL (p=0.000), and male partners with untreated tuberculosis history were more prone to idiopathic PRL [treated tuberculosis history vs. untreated tuberculosis (OR 29.557, 95 % CI 6.437–135.708, p=0.000), no tuberculosis history vs. untreated tuberculosis history (OR 73.856, 95 % CI 13.139–415.150, p=0.000)]. Spearman correlation showed that the prevalence of tuberculosis in male partners was positively correlated with DFI (R=0.492, p=0.000) and negatively correlated with testosterone (R=−0.120, p=0.012). Conclusions Among the couples with idiopathic PRL, male partners with a history of pulmonary tuberculosis (especially untreated pulmonary tuberculosis) are more prone to PRL, which maybe caused by high DFI and low testosterone.

Objectives Serum lactate and albumin levels upon admission are independent risk factors for poor prognosis in patients with cardiogenic shock (CS). The association between the serum lactate/albumin ratio (LAR) and mortality in patients with cardiogenic shock remains unclear. This study aims to explore the relationship between LAR at admission and the 90-day mortality of patients with CS. Methods We performed a secondary analysis of previously published data on cardiogenic shock patients. Based on the curve, an LAR of >0.094 indicated a harmful threshold. The outcomes of cardiogenic shock Patients dichotomized according to the LAR cut-off value. Univariate logistic regression models, the receiver operating characteristic (ROC) curve in the multivariate analysis, a restricted cubic spline plot derived from multivariate logistic regression, Decision curve analysis and subgroup analyses were employed to investigate the association between LAR and mortality of cardiogenic shock. Results A total of 176 patients were included. Univariate logistic analyses revealed a positive association between LAR and 90-day mortality of cardiogenic shock patients (HR 4.50, 95 % CI=2.64–7.66, p<0.001). The Area Under the Curve (AUC) value for LAR was 0.781 (95 % CI: 0.713–0.848), which was higher than that for initial lactate (AUC=0.768) and albumin (AUC=0.652) alone. It was not inferior even when compared to IABP-SHOCK II score (AUC=0.719). The restricted cubic spline analysis demonstrated a linear relationship between baseline LAR and the mortality of patients with cardiogenic shock. The Kaplan-Meier curves indicate lower survival rates in patients with LAR values >0.094. Decision curve analysis shows that LAR model has the best utility in intermediate-risk clinical decisions (30–75 % threshold). The final subgroup analysis showed no significant interaction of LAR with each subgroup (P for interaction: 0.057–0.948). Conclusions The baseline Lactic/albumin Ratio (LAR) in patients experiencing cardiogenic shock shows a positive correlation with mortality associated with this condition. The findings indicate a significant increase in the mortality rate when the LAR exceeds a certain threshold. Furthermore, the LAR serves as an independent risk factor for poor prognosis in patients suffering from cardiogenic shock, with superior prognostic performance than initial lactate or serum albumin alone. Clinicians use LAR for personalized risk assessment when they encounter a medium probability scenario for 90-day mortality.

Objectives To investigate the effects of swimming on bone loss and the OPG/RANKL/RANK pathway in ovariectomized (OVX) osteoporotic rats. Methods Twenty female SD rats were randomly divided into a sham-operated group, a ovariectomized osteoporosis group, a short-duration exercise group, and a long-duration exercise group. Bone volume fraction (BV/TV), trabecular thickness (Tb.Th), bone mineral density (BMD), trabecular separation (Tb.Sp), and trabecular number (Tb.N) of bone tissue were measured by Micro-CT. The expression of human C-terminal peptide collagen type I (CTX-Ⅰ), tartrate-resistant acid phosphatase 5b (TRAP-5b), bone-specific alkaline phosphatase (BALP) and serum bone glycoprotein (BGP) were measured by ELISA. The mRNA and protein expression of OPG, RANKL, and RANK in bone tissue were detected by qRT-PCR and Western bolt, respectively. Results After swimming treatment, compared with the ovariectomized osteoporosis group, BV/TV, BMD, Tb.Th, and Tb.N increased, while Tb.Sp decreased; CTX-Ⅰ, TRAP-5b, BGP, and BALP levels decreased. OPG mRNA and protein expression increased, while RANKL and RANK decreased. Conclusions Swimming training alleviated ovariectomy-induced bone loss and was accompanied by a shift of the OPG/RANKL/RANK axis toward an anti-resorptive profile, suggesting that modulation of this pathway may contribute to the bone-protective effects of swimming. Further functional studies are warranted to test causality.

Objectives This study aimed to investigate the expression of programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) on CD4 + and CD8 + T cells in children with asthma and their relationship with Th2-associated inflammatory cytokines (IL-4, IL-5, and IL-13). The goal was to elucidate the potential roles of these immune checkpoint molecules in asthma pathogenesis and severity. Methods A prospective observational study was conducted involving 112 asthmatic children aged 5–15 years and 100 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to analyze the frequencies of PD-1 + and LAG-3 + T cells. Serum levels of IL-4, IL-5, and IL-13 were measured using ELISA. Asthma severity was classified according to the Global Initiative for Asthma (GINA) guidelines, and demographic, clinical, and lung function data were collected. Statistical analyses included Pearson correlation, ROC curve analysis, and logistic regression to assess the diagnostic and prognostic value of PD-1 and LAG-3 expression. Results Asthmatic children, particularly those with moderate-to-severe disease, exhibited significantly higher frequencies of PD-1 + and LAG-3 + T cells compared to healthy controls. Serum levels of IL-4, IL-5, and IL-13 were also elevated in asthmatic children, with the highest levels observed in moderate-to-severe cases. The frequencies of PD-1 + LAG-3 + T cells were positively correlated with IL-13 levels and negatively correlated with lung function parameters, including FVC%, FEV1%, and PEF%. ROC curve analysis demonstrated that CD4 + PD-1 + LAG-3 + T cells had superior diagnostic performance for moderate-to-severe asthma. Logistic regression identified CD4 + LAG-3 + PD-1 + , and IL-13 as independent risk factors for moderate-to-severe asthma. Conclusions The elevated frequencies of PD-1 and LAG-3 on T cells in asthmatic children, particularly in those with moderate-to-severe disease, suggested that these immune checkpoint molecules play a critical role in asthma pathogenesis and severity. These findings highlighted the potential of PD-1 and LAG-3 as biomarkers for asthma severity and therapeutic targets, offering new avenues for immune modulation in pediatric asthma management.

Objective Gasdermin D (GSDMD), a key pyroptosis effector, is implicated in systemic inflammation during sepsis. However, its role in skeletal muscle metabolism remains largely unexplored. Methods GSDMD-knockout (GSDMD-KO) and wild-type (WT) mice were used to establish a septic model. Skeletal muscle samples were collected and subjected to non-targeted metabolomic analysis via UHPLC-QE-MS. Multivariate statistical analysis and KEGG pathway enrichment were performed to identify differential metabolites and explore the underlying metabolic alterations. Results GSDMD knockout resulted in significant changes in skeletal muscle metabolism, notably in pathways related to taurine and hypotaurine metabolism, amino acid biosynthesis, bile acid biosynthesis, oxidative stress response, and nucleotide metabolism. These alterations suggest that GSDMD regulates energy, amino acid, lipid, and redox metabolism during sepsis. A panel of potential biomarkers was identified, which may contribute to muscle injury and repair. Conclusions GSDMD deficiency profoundly alters skeletal muscle metabolic profiles in sepsis. Identified metabolites may serve as diagnostic markers and therapeutic targets for sepsis-associated myopathy, offering insights into GSDMD’s role in muscle metabolism and potential intervention strategies.

Objectives To determine the safety and effectiveness of the anticoagulation regimen nafamostat mesylate for continuous renal replacement therapy in patients with sepsis-associated AKI. Methods According to the inclusion and exclusion criteria, a total of 42 patients with sepsis and complicated renal function impairment who required CRRT were included. Among them, 2 patients were excluded because their admission time was less than 24 h. Finally, 40 patients were included. The Nafamostat mesylate anticoagulation method was selected for the experimental group and regional citrate anticoagulation was used in the control group. Results At admission (experimental group vs. control group), the following findings were obtained: sCr: 391.2 ± 1.94 vs. 389.7 ± 1.46 ummol/L, BUN: 12.97 ± 1.51 vs. 11.86 ± 1.75 mmol/L, APTT: 23.43 ± 1.27 vs. 24.12 ± 1.53 s, and Plt: 80.15 ± 12.27 vs. 83.15 ± 10.35 × 109/L. Four hours after CRRT treatment, the following findings were obtained: sCr: 280.85 ± 1.89 vs. 283.41 ± 1.46 ummol/L, BUN: 12.02 ± 1.55 vs. 11.86 ± 1.75 mmol/L, APTT of prefilter: 41 ± 3.89 vs. 25.31 ± 2.17 s, postfilter: 81.63 ± 3.76 s, Plt: 80.2 ± 13.04 vs. 83.15 ± 10.35 × 109/L, and pH 7.37 ± 0.03 vs. 7.41 ± 0.02. A comparison of sCr and APTT (prefilter) revealed that p<0.05 was statistically significant, but there was no significant difference in the other indicators. In the control group, citrate accumulation occurred in 2 patients; for a total calcium/arterial calcium ion concentration >2.5, there were no obvious adverse reactions. The lifespans of the first filter were 60.2 ± 10.09 and 59.07 ± 11.44 h, and the ICU lengths were 7.35 ± 1.35 and 7.21 ± 1.17 days, Nafamostat mesylate prolonged filter lifespan compared to RCA, however, ICU LOS was same. Conclusions The anticoagulation regimen of nafamostat mesylate may be safe and effective in patients with sepsis-associated AKI receiving CRRT.

Objectives Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major clinical and public health threat due to its high mortality in sepsis and the complexity of its resistance mechanisms, which greatly limit therapeutic effectiveness. Outer membrane vesicles (OMVs) secreted by Gram-negative bacteria harbor various virulence factors and resistance determinants, and may facilitate long-distance pathogenic communication. However, the OMV protein composition of CRKP isolated from sepsis patients remains poorly understood. This study aimed to characterize the protein cargo of OMVs derived from clinical CRKP isolates and to identify differential proteins and pathways associated with bacterial pathogenicity and carbapenem resistance. Methods Three CRKP and three carbapenem-sensitive  K. pneumoniae  (CSKP) were isolated from blood cultures of patients with sepsis, and then their OMVs were extracted. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and SDS-PAGE were used for characterization. Quantitative proteomic profiling was performed using LC–MS/MS, followed by differential expression analysis, Gene Ontology (GO), KEGG pathway enrichment, and protein–protein interaction (PPI) network analysis. Results A total of 1,193 OMV proteins were identified, with CRKP-OMVs containing substantially more unique proteins (140 vs. 5 in CSKP-OMVs) and significantly increased overall protein abundance. Among the 199 differential proteins, 180 were upregulated in CRKP-OMVs. Most differential proteins were localized to the membrane or cytoplasm, and were enriched in enzymatic functions and pathways including β-alanine metabolism, O-antigen nucleotide sugar biosynthesis, Lipopolysaccharide biosynthesis, and β-lactam resistance. Key proteins such as adhE, NDK, treA, and ackA were markedly elevated, while galE and Ter family proteins were uniquely present in CRKP-OMVs, indicating potential roles in resistance and pathogenicity. Conclusions CRKP-derived OMVs from sepsis patients exhibit distinct protein enrichment patterns associated with membrane functions, metabolic remodeling, and antibiotic resistance. These findings provide insights into CRKP pathogenesis and highlight candidate OMV-associated proteins that may serve as targets for antimicrobial strategies or vaccine development.

Objectives To investigate the surgical outcomes of coronal shear fractures of the capitellum and trochlea (CSFCT) guided by the Dubberley classification. Methods A retrospective analysis was conducted on patients with CSFCT between January 2015 and December 2023. Demographic information, surgical details, functional recovery outcomes, and postoperative complications were recorded and compared across fracture subgroup. Results 39 patients were included (mean age: 44.3 ± 15.5 years) with a mean follow-up of 38.2 ± 12.0 months. All patients underwent surgery via an extended lateral approach using various hardware. Postoperatively, the mean extension deficit was - 0.9°, mean flexion was 126.4°, and mean flexion-extension arc was 125.4°. The mean Mayo Elbow Performance Scores (MEPS) was 87.9 (66.7 % excellent, 30.8 % good, 2.5 % fair). Dubberley type 2 and A fractures had higher MEPS than type 3 and B, respectively (both p<0.01). Postoperative complications included two elbow stiffness, two implant prominence, and one avascular necrosis case. Conclusions Under the guidance of the Dubberley classification, surgical treatment for patients with CSFCT has achieved greater efficacy, favorable outcomes, and low complication rates.

Objectives To develop a comprehensive understanding of psychological distress and associated sociocultural and disease related factors among South Asian Individuals with COPD. Methods A convergent mixed methods study was used. The quantitative sample included 408 and qualitative sample included 22 individuals (11 patients and 11 family caregivers). Hospital Anxiety and Depression Scale was used for quantitative data collection and semi-structured interviews for qualitative phase. Descriptive and regression analyses were used for quantitative data and reflexive thematic analysis for qualitative data. Qualitative and quantitative data were integrated using merging integration procedure and statistics-theme joint display. Results The mean depression score was 10.91 ± 2.42 and the anxiety score was 9.91 ± 2.69. Quantitative and qualitative integrated data showed that factors affecting psychological distress included sex, education level, primary decision maker in the household, years of living with COPD, financial constraints, fears of the future, self-care struggles, interrupted family decision-making process, and relational support. Conclusions Individuals with COPD reported moderate to high levels of psychological distress influenced by societal, family, and disease related factors. Community based programs are also needed for providing adequate mental health and counselling resources to patients and their family caregivers.

Objectives Delirium is a common but frequently underdiagnosed complication in adult intensive care units (ICU), associated with increased morbidity, mortality, and healthcare costs. Early detection using validated tools is essential. This study aim to translate, adapt, and validate the Confusion Assessment Method for Intensive Care Units flowsheet (CAM-ICU flowsheet) into European Portuguese. Methods A methodological, cross-sectional, descriptive-correlational study was conducted in a northern Portuguese ICU. The CAM-ICU flowsheet was translated and back-translated, followed by expert validation. Forty-two adult ICU patients on invasive mechanical ventilation were assessed using the adapted tool by two trained observers. Diagnostic accuracy was evaluated using DSM-5 criteria as the gold standard. Statistical analysis included sensitivity, specificity, kappa coefficient, and ROC curves. Results Delirium was detected in 57.1 % of patients. The CAM-ICU flowsheet in European Portuguese demonstrated high interobserver agreement (κ=0.952), excellent sensitivity (100 %), and specificity (81.8–86.3 %). ROC AUC ranged from 0.909 to 0.932. The inattentiveness feature was the core for the presence or absence of delirium. Conclusions The CAM-ICU flowsheet in European Portuguese was validated to assess delirium in nonverbal ICU patients on mechanical ventilation through this study and demonstrated to be a reliable and valid tool.

Objectives Diabetic retinopathy (DR) is a severe complication of diabetes mellitus (DM) leading to vision loss and blindness, which typically develops 12–20 years after the diagnosis of DM. Anxiety and depression frequently co-occur with chronic medical conditions like DM and DR, impacting their onset, course, and prognosis. This study aimed to examine the link between anxiety, depression, DR, and macular changes. Methods A cross-sectional study was conducted at the Clinic for Ophthalmology, University Clinical Center Niš, Serbia, involving 80 adult participants, naïve to psychiatric and invasive ophthalmological therapy, divided into two groups: 40 patients with DR, and 40 healthy controls. Ophthalmic examinations, biochemical measurements, and assessments of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and Montgomery and Asberg Depression Rating Scale (MADRS) were performed. Results Results indicated that patients with DR had significantly higher levels of anxiety and depression compared to controls. The study found no significant correlation between HADS and MADRS scores with patients’ gender, type of therapy, or the type of DR. However, a higher HADS and MADRS score was observed in patients with left-side OCT macular edema. Conclusions The study highlights the complex interaction between psychiatric disorders and somatic illnesses, emphasizing the need for comprehensive care strategies that address both physical and mental health to improve patient outcomes.

Objectives This meta-analysis evaluates Janus Kinase (JAK) inhibitors’ efficacy and safety in large vessel vasculitis (LVV), encompassing Giant Cell Arteritis (GCA) and Takayasu’s Arteritis (TAK). Methods Registered on PROSPERO (CRD42024575313), four databases were systematically searched for randomized controlled trials (RCTs) and observational studies. Outcomes included remission/relapse rates and adverse events, assessed with sensitivity/publication bias analyses. Results Five studies (107 patients: 65 GCA, 42 TAK) showed pooled 12-month remission rates of 80.1 % (95 % CI: 68.3–92.0), with subgroup rates of 87.3 % (GCA) and 69.6 % (TAK). Relapse rates were 11.3 % overall (2.5 % GCA vs. 22.9 % TAK). Adverse event-related discontinuation was 4.4 %, with subgroup rates of 4.0 % (GCA) and 4.2 % (TAK). Conclusions JAK inhibitors demonstrate favorable efficacy and safety in LVV.

Objectives This study assessed the relationship between glycated serum protein (GSP) and post-reflux swallow-induced peristaltic wave (PSPW) index and esophageal baseline impedance (BI) in patients with diabetes mellitus (DM) with gastroesophageal reflux disease (GERD). Methods General clinical data of patients in the DM and DM/GERD groups were compared. Multifactorial Logistic regression analyses were performed to screen for independent factors on GERD in DM patients, and odds ratio (OR) was calculated. The risk of GERD was assessed using a spline regression model constructed on the basis of GSP, PSPW and BI. Predictive efficacy was analyzed using Receiver operating curve (ROC) curve analysis. Results Statistically significant differences were found in TG, hs-CRP, GSP, PSPW, and BI between patients in the DM and DM/GERD groups. PSPW and BI (OR=0.99, p<0.01) were independent protective factors, and elevated GSP was an independent risk factor for the development of GERD. A linear relationship was validated between GSP and PSPW and BI and the prevalence risk of developing GERD in patients with DM, all with good predictive efficacy. Conclusions GSP, PSPW, and BI show significant correlations with the onset and progression of GERD in patients and all demonstrate good predictive efficacy. However, due to the small size of the patient cohort, the generalizability of these findings requires further validation.

Objectives The study aimed to investigate the nephroprotective effects of visnagin on renal ischemia-reperfusion (I/R) injury and the role of M1/M2 macrophage polarization in this process. Methods Forty-two adult rats were divided into six groups: Control, Visnagin30 mg/kg, Visnagin60 mg/kg, I/R, I/R + Visnagin30 mg/kg, I/R + Visnagin60 mg/kg (n=7). Bilateral renal ischemia was induced by clamping for 25 min, followed by 2 h of reperfusion. Visnagin or vehicle was administered to the animals intraperitoneally 2 h before reperfusion. At the end of the study, kidney samples were collected for analysis of oxidative stress, inflammatory cytokines, apoptotic protein expression, and M1/M2 macrophage polarization. Results I/R injury increased malondialdehyde (MDA), chemiluminescence (CL), IL-1β, and IL-6 levels while decreasing glutathione (GSH) in renal tissue, indicating enhanced oxidative stress (p<0.001) and inflammation (p<0.05). Histopathological examination showed glomerular atrophy, tubular degeneration, and intertubular hemorrhage. Visnagin treatment at 60 mg/kg significantly reduced MDA, CL, and IL-1β levels, and increased GSH (p<0.05). Immunohistochemically, visnagin decreased Bax (p<0.001), caspase-3 (p<0.01), and TNF-α (p<0.01) expressions elevated by I/R injury. Furthermore, visnagin reversed I/R induced M1/M2 macrophage polarization (CD86↑, CD163↓), decreasing CD86 (p<0.05) and increasing CD163 immunodensity (p<0.05). Conclusions Visnagin treatment (60 mg/kg) exerts promising nephroprotective effects in renal I/R injury by reducing oxidative stress, inflammation, apoptosis, and modulating M1/M2 macrophage polarization.

Objectives To evaluate the preventive and corrective effects of vitamin D on antioxidant defense and blood rheology in rats with streptozotocin (STZ)-induced diabetes mellitus. Methods Forty male rats (10 weeks old, ∼200 g) were randomly assigned to four groups: Group I – Intact controls; Group II – Diabetic rats (STZ only); Group III – Preventive (vitamin D for 14 days before STZ and continued throughout the experiment); Group IV – Therapeutic (vitamin D from day 3 post-STZ). DM was induced with streptozotocin (30 mg/kg), and vitamin D was administered orally at 300 IU/day, according to a previous dose-control experiment. Data from the 21st experimental day were evaluated. Blood samples collected at this point were used to determine catalase (CAT), superoxide dismutase (SOD), and blood rheological parameters. Results Vitamin D supplementation enhanced antioxidant-related parameters and improved blood rheological indices, particularly when administered therapeutically. Conclusions Vitamin D shows therapeutic potential in attenuating oxidative imbalance and improving blood rheology in streptozotocin-induced diabetes mellitus.

Objectives The aim of this study was to explore the predictive value of the C-reactive protein-to-body mass index ratio (CBR) in the prognosis of all-cause mortality in patients with heart failure (HF) with different ejection fractions. Methods We included 1196 HF patients from the First Affiliated Hospital of Kunming Medical University after exclusion criteria. Based on the optimal cut-off value from the ROC curves, patients were categorised into low CBR group and high CBR group. The predictive value of the CBR for the prognosis of all-cause mortality in patients with different types of HF was assessed using Kaplan–Meier curves, Cox proportional hazards analyses, cubic spline plots and ROC curves analyses. Results Kaplan‒Meier analyses showed that the high CBR group had the highest cumulative incidence of all-cause mortality regardless of the type of HF patients. Multivariate Cox regression analysis revealed that the CBR was an independent predictor of prognosis for all-cause mortality in patients with all types of HF. The cubic spline plots showed a roughly positive association between the CBR and all-cause mortality. The ROC curves showed that for all types of HF patients, the area under the curve for the CBR was the largest relative to individual CRP and BMI. Conclusions Regardless of the type of HF patients, the CBR can be a good predictor of prognosis for all-cause mortality in patients with a higher CBR associated with a higher risk of all-cause mortality.

Objectives To characterize the patterns, risk factors, and reporting trends of adverse drug reactions (ADRs) in a tertiary care hospital in China to inform targeted medication safety interventions. Methods A single-center, retrospective analysis was conducted on 5,564 ADR reports extracted from the National Adverse Drug Reaction Monitoring System (2019–2024). Reports were assessed for causality using the WHO-UMC criteria. Descriptive statistics and chi-squared tests were employed to analyze demographics, reporting trends, causative drugs, administration routes, and clinical outcomes. Results The mean patient age was 62.4 years, with males slightly predominating (52.5 %). ADR reporting increased markedly over the study period, with pharmacists becoming the primary reporters (93.1 % in 2024). Intravenous infusion was the most common route (67.3 %). Antineoplastic agents were the predominant drug class implicated (34.2 %), followed by anti-infectives (10.8 %) and cardiovascular drugs (9.4 %). Statistically significant associations were found between ADR outcomes and both the type of ADR (new/serious vs. general, p<0.001) and the administration route (intravenous vs. oral, p<0.001). No significant association was observed between patient age and ADR outcomes (p=0.244). Conclusions Antineoplastic drugs and intravenous administration are key ADR risk factors. Enhanced monitoring of high-risk medications and optimized infusion protocols are needed. Limitations include retrospective single-center design and reporting biases.

Background Streptococcus intermedius is a major human pathogen associated with invasive diseases such as meningitis and endocarditis. These infections may lead to inflammation, fever, and cardiac damage. At present, no effective vaccine exists for prevention. Objectives This study aimed to design a stable, non-allergenic, and antigenic chimeric multi-epitope vaccine against S. intermedius using Immunoinformatics approaches. Methods Twelve B-cell, five helper T lymphocyte (HTL), and five cytotoxic T lymphocyte (CTL) epitopes were predicted using advanced immunoinformatics tools. These epitopes were assembled into a single vaccine candidate. The construct was evaluated in silico for its antigenicity, allergenicity, and physicochemical stability. A 3D structural model of the vaccine was generated and validated. Molecular docking and dynamics simulations were conducted to assess interactions between the vaccine and immune receptors: TLR4, TLR3, MHC-I, and MHC-II. Results The final vaccine candidate demonstrated favorable antigenic and non-allergenic properties, along with high stability. Structural validation confirmed proper folding. Docking analyses revealed strong binding affinities between the vaccine and target immune receptors. Molecular dynamics simulations indicated stable complexes, supporting the construct’s immunological compatibility. Conclusions The designed chimeric multi-epitope vaccine shows strong potential to elicit an immune response against S. intermedius . These findings provide a foundation for further experimental validation through in vivo and clinical trials.

Objectives This study aimed to design and evaluate a computationally constructed multiepitope vaccine targeting Simian Virus 40 (SV40) by predicting and selecting immunogenic B-cell and T-cell epitopes derived from the VP1 and VP2 capsid proteins using bioinformatics approaches. Methods B and T-cell epitopes from VP1 and VP2 were predicted and screened for antigenicity, non-allergenicity, and non-toxicity. Structural modeling and validation were performed using PSIPRED, trRosetta, and a Ramachandran plot. Population coverage was assessed using the IEDB. Molecular docking with TLR3 and TLR5, immune simulations, in silico cloning, and molecular dynamics simulations were used to evaluate binding, expression, and structural stability. Results Molecular docking with human receptors TLR3 and TLR5, revealing strong binding affinities of −1,008.3 kcal/mol and −1,309.2, and further validated using MD simulation analysis. The in silico expression analysis, performed using the SnapGene tool, indicated high expression levels in the pBR322 vector. The immune simulation analysis showed that the vaccine has a high capacity to induce an immune response in the host. Conclusions The designed vaccine demonstrated high immunogenic potential; further in vitro and in vivo studies are needed to verify the antigenic potential and safety of the designed vaccine.

Objectives Total knee and hip replacements are among the most common surgical procedures. Optimization of the treatment process is of great relevance and requires verification of effectiveness in different settings. The PROMISE study was carried out to achieve this. Methods An optimized treatment process was implemented in 3 German hospitals with different levels of care. A total of 1,887 patients were included. The WOMAC Score was established as the outcome parameter at 3, 6 and 12 months after surgery. A mixed model for repeated measurements was used to estimate site-specific effects as well as the limits of the corresponding confidence intervals. To demonstrate homogeneous results across all sites, these outcomes needed to fall within a range defined by the overall effect ± the minimally clinically important difference (MCID), using a 95 % confidence interval. Results All site-specific results ranged from (points [CI-limits]) −29.2 [−29.7; −28.7] to −24.4 [−24.5; −24.3] and were therefore within the range defined by the overall treatment effect and the MCID (25.4 ± 10). Conclusions We could demonstrate homogeneous site-specific effects of the optimized process in the three most different settings of the German healthcare system. Therefore, an essential prerequisite for a system-wide rollout has been met.

Objectives This study aims to systematically evaluate the incremental value of admission eosinopenia EOS(−) in enhancing the predictive efficacy of early-stage acute respiratory distress syndrome (ARDS) risk models for ICU patients. Methods This study employed a single-center retrospective cohort design, enrolling 482 adult ICU patients between 2020 and 2023. Using Cox proportional hazards regression, we constructed and compared three models: Model 1 (baseline clinical model) included age, pneumonia, sepsis, and SOFA score; Model 2 added lymphocytes and eosinophils to Model 1; Model 3 further adjusted for BMI and diabetes. Predictive performance was assessed using the C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI), and validated internally. Results C-statistics for Models 1, 2, and 3 were 0.683, 0.710, and 0.729, respectively. Model 3 demonstrated optimal performance (NRI=0.185, p=0.004), with an adjusted C-statistic of 0.695. Multivariate analysis identified age, pneumonia, and sepsis as independent ARDS risk factors, while EOS(−) showed non-independence. Results from competing risks analysis were consistent with the primary analysis conclusions. Conclusions Although eosinopenia is not an independent predictor of ARDS, it provides incremental information for early risk stratification based on conventional clinical factors, thereby aiding in the identification of high-risk patients.

Objectives This study examined the mediating effects of physical activity (PA) and basal metabolic rate (BMR) on the relationship between years since menopause and sarcopenia in community-dwelling elderly women. Methods Based on AWGS 2019 criteria, 718 women aged ≥65 were classified into sarcopenia, possible sarcopenia, and control groups. Multiple logistic regression and mediator models were used to assess associations. Results BMR correlated with grip strength (r=0.292), ASMI (r=0.750), and years since menopause (r=−0.246). Years since menopause negatively correlated with grip strength and SPPB (r=−0.315, −0.381; p<0.05). It was a risk factor for possible sarcopenia (OR=1.05; 95 % CI: 1.03–1.08). Low BMR and medium PA (vs. high) increased sarcopenia risk (OR=0.95 and 2.72, respectively). Direct effect of years since menopause was β=−0.010 (p=0.001); total mediating effect was 0.019 (p<0.001), mainly through BMR (0.007) and PA (0.001). Conclusions PA and BMR mediate the effect of years since menopause on sarcopenia risk. Longer duration since menopause decreases PA and BMR, elevating sarcopenia risk.

Abstrast Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy associated with a poor prognosis and considerable resistance to conventional therapies. While radical surgery may offer benefit for a subset of patients with early-stage disease, recent decades have witnessed notable progress in immunotherapy, yielding encouraging outcomes across both hematologic cancers and solid tumors in preclinical and clinical settings. Despite these advances, PDAC remains largely refractory to current immunotherapeutic strategies, owing largely to its unique tumor microenvironment (TME). The TME plays a pivotal role in modulating tumor progression, metastatic dissemination, and treatment response. It is commonly marked by a profoundly immunosuppressive milieu that attenuates effective anti-tumor immunity and complicates therapeutic intervention. The complex cellular and molecular composition of the TME poses significant challenges for the development of novel treatment modalities. Consequently, there is a growing imperative to therapeutically “reprogram” various components and functions within the TME to improve clinical outcomes in PDAC patients. This review seeks to elucidate how the PDAC TME and its key immunosuppressive constituents influence disease progression and response to immunotherapy. A deeper understanding of these interactions may open avenues for innovative treatment approaches capable of overcoming the barriers imposed by the TME in pancreatic cancer.

Background Sepsis-induced myopathy (SIM)significantly contributes to long-term disability and mortality among sepsis survivors. A comprehensive understanding of both the molecular mechanisms and rehabilitation strategies is crucial for effective management. Methods A review of pertinent studies was conducted, focusing on the molecular pathogenesis, therapeutic strategies, and rehabilitation interventions for SIM, with particular attention to clinical and translational advancements. Results Current management strategies encompass infection control, modulation of inflammation, nutritional support, and structured rehabilitation programs, including early mobilization and physiotherapy. Emerging therapies that target inflammation, cellular protection, and regeneration – such as stem cell therapy and gene-editing techniques – demonstrate potential. Furthermore, advancements in personalized medicine, including genomics, transcriptomics, and individualized metabolic interventions, may further improve outcomes. Conclusions Optimizing both mechanistic and rehabilitation strategies is essential for enhancing functional recovery and quality of life in patients with SIM. An integrated clinical and molecular approach presents the most promising path forward. Keywords: sepsis-induced myopathy, sepsis.

Lung cancer presents a major global public health challenge due to its high incidence and mortality rates, highlighting the urgent need for effective treatment strategies. Radiotherapy, a cornerstone in lung cancer treatment, faces significant limitations due to both intrinsic and acquired radioresistance in tumors. Recent researches have identified long non-coding RNAs (lncRNAs) as critical regulatory factors that significantly affect the radiosensitivity of lung cancer cells. These lncRNAs are involved in key biological processes, including DNA damage repair, apoptotic signaling, cell cycle progression, tumor microenvironment remodeling. This review comprehensively summarizes and discusses the molecular mechanisms by which lncRNAs influence radiosensitivity and assesses their potential as predictive biomarkers for radiotherapy. Additionally, it analyzes the potential of lncRNA-based intervention strategies to overcome radioresistance and enhance radiotherapy regimens. The goal is to provide a robust theoretical foundation for advancing precision radiotherapy in lung cancer. In summary, lncRNAs function as multidimensional regulators of lung cancer radiosensitivity and represent promising targets for radiosensitization in the precision medicine era.

Introduction This narrative review describes the scientific evidence on drug-induced gingival overgrowth (DIGO) in kidney transplant patients treated with immunosuppressive agents, particularly Cyclosporine A, focusing on its prevalence, pathogenetic mechanisms, and clinical management strategies. Content This study was conducted including PubMed, Scopus, and Web of Science, highlighting clinical studies and case reports. Summary DIGO is an oral complication in transplant patients treated with cyclosporine A, and its frequency may increase when combined with calcium channel blockers. However, tacrolimus has shown a lower incidence of DIGO compared with Cyclosporine A, making it a favorable therapeutic alternative in immunosuppressive regimens for renal transplant patients. Mycophenolate mofetil, despite being less directly linked to DIGO, can exacerbate gingival changes when combined with other immunosuppressants by promoting inflammation and connective tissue remodeling. Sirolimus is associated with a lower risk of DIGO compared with calcineurin inhibitors; however, some isolated cases have been reported, particularly in patients previously exposed to Cyclosporine A or when used in combination with calcium channel blockers. Management strategies include proper oral hygiene, dose adjustment or medication substitution, and, in some cases surgical intervention. Outlook The fundamental keys to reducing its incidence and severity are a personalized immunosuppressive regimen with a multidisciplinary approach.

Objectives Coronary artery anomalies are rare both in coronary angiogram and computed tomography angiography. Hypertrophic cardiomyopathy (HCM) is the most frequent inherited cardiac disease. The phenotype of HCM associated with anomalous coronary origin is not commonly seen especially in children. Case presentation We describe a case series of two children with HCM combined right coronary artery (RCA) originated from left coronary sinus. Case 1 was a 9-month-old female with TTN gene heterozygous mutation ( p.R16724L ) who exhibited cardiac insufficiency. Case 2 was a 12-year-old male with MYBPC3 gene heterozygous mutation ( p.R820Q ) who only exhibited intermittent chest pain. A total of 7 HCM cases with RCA originated from left coronary sinus have been reported with our literature review. Case 1 is the youngest child patient in our report until now. Moreover, the echocardiogram of case 1 is similar with restrictive cardiomyopathy (RCM) and it demonstrates the progression of HCM to heart failure. So, HCM with TTN gene mutation may exhibit cardiac insufficiency more early. And the gene mutation site of TTN has never been reported in previous HCM cases. Conclusions HCM coexisted with anomalous origin of RCA has different clinical presentation, and it maybe due to different gene mutation.

Objectives Congenital acute megakaryoblastic leukemia (AMKL) is an extremely rare and aggressive malignancy with poor prognosis. Case presentation We report a female neonate with Down syndrome (DS) who presented with respiratory distress and hepatomegaly at birth. Laboratory evaluation revealed hyperleukocytosis (253.45 × 10 9 /L) and bone marrow studies confirmed AMKL with trisomy 21. Remarkably, spontaneous hematologic remission occurred within 2 months without chemotherapy. Conclusions This case highlights the unique clinical course of DS-associated AMKL and underscores the potential for spontaneous regression in congenital leukemia.

Objectives Severe tricuspid regurgitation (TR) can be a phenotypic manifestation of an underlying disease process that is the primary driver of patient prognosis. Associated clinical signs such as small vein pulsations are similarly prognostic. Systolic propulsion of the eyeballs is an extreme manifestation of severe TR with only seven reported cases in the literature. We herein report two additional cases, review the available literature, and discuss prognostic implications of this phenomenon. Case presentation Two patients with severe tricuspid regurgitation and systolic propulsion of the eyeballs are described in a comprehensive manner. Unlike previous reports, we include contemporary high-quality images and video of the phenomenon in addition to the most in-depth review of the literature on this subject to date. Conclusions Systolic propulsion of the eyeballs is a manifestation of severe tricuspid regurgitation in the background of profound right ventricular dysfunction. We believe this is a rare clinical sign that carries ominous prognostic implications.

Objectives To develop and validate machine learning (ML) models for identifying key predictors and estimating the risk of intraoperative hypotension (IOH) in elderly patients undergoing general anesthesia. Methods This secondary analysis included 1,720 elderly surgical patients from a randomized controlled trial. Data were split chronologically into training sets. Feature selection was performed using univariate analysis and the Boruta algorithm. Eight ML models – logistic regression, Bayesian model, K-nearest neighbor, support vector machine, neural network, classification and regression tree, extreme gradient boosting, and random forest – were developed with cross-validation, hyperparameter tuning, and random oversampling. Model performance was evaluated using ROC, PRC, calibration, and decision curve analyses, and interpretability was enhanced using SHapley Additive exPlanations (SHAP). Results Key predictors included anesthesia protocol, Charlson comorbidity index, preoperative sodium, creatinine, BUN/creatinine ratio, intraoperative drug use (e.g., sevoflurane, lidocaine, morphine), preoperative MAP and MHR, surgical and anesthesia duration, and surgical site. The random forest model achieved the best performance (accuracy=0.9917; MCC=0.9832; AUC-ROC=0.9998; AUC-PRC=0.9998). Conclusions A robust ML-based model was established to accurately predict IOH in elderly patients. These findings may support individualized anesthesia management and targeted preventive strategies to reduce IOH incidence.

Objectives To analyze differences in coagulation function and plasma inflammatory factors between type 2 diabetes mellitus (T2DM) patients with and without ischemic stroke (IS), and explore related mechanisms. Methods 50 patients with T2DM complicated with IS (experimental group, EG) and 50 patients with simple T2DM (control group, CG) were retrospectively included, while 30 healthy volunteers served as the blank group (BG). The expression levels of plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB) in the EG were significantly elevated as against the CG and the BG (p<0.05). Results As against the CG and the BG, activated partial thromboplastin time (APTT) and prothrombin time (PT) levels were significantly reduced, while the plasma fibrinogen (FIB) and D-Dimer (DD) levels were significantly elevated in the EG; The incidence of postoperative complications in the EG (13.46 %) was significantly reduced as against the CG (21.15 %) (p<0.05). IL-6 was notably negatively correlated with APTT (p = 0.002, r= −0.432); it was extremely significantly negatively correlated with PT (p = 0.000, r= −0.536); it was notably positively correlated with plasma FIB content (p = 0.001, r= 0.445). Conclusions The coagulation function and peripheral blood inflammatory markers in patients with T2DM complicated by IS were significantly different compared to those in patients with T2DM alone and healthy volunteers. The correlation between inflammatory markers and coagulation indicators ( e.g., the negative correlation between IL-6 and APTT/PT) identified in this study holds important clinical significance. It provides new insights for thrombosis risk stratification and personalized antithrombotic treatment in T2DM patients. Monitoring the levels of inflammatory markers may optimize thrombosis prevention strategies and enhance the precision of clinical diagnosis and treatment.

Objectives The radiation-induced bystander effect (RIBE) is a destructive reaction that occurs in non-irradiated cells. Exosomes, as an important intercellular information carrier, are considered potential mediators of RIBE, but their role in B cells remains unclear. Methods B cell line IM-9 cells were irradiated to obtain exosomes for small RNA sequencing, and cell assays were used to assess the key miRNA’s role in non-irradiated B cell ferroptosis. Results Exosomes isolated from irradiated and non-irradiated B cells were well characterized, displaying typical cup-shaped morphology (50–150 nm) and expressing exosomal markers ALIX and TSG101. miR-34a-5p was identified to be a key miRNA in regulating ferroptosis, and significantly upregulated in irradiated B cell derived exosomes (IR-exo). IR-exo remarkedly promoted ferroptosis of non-irradiated IM-9 cells, as evident by enhanced lactate dehydrogenase activity and lipid peroxidation, and reduced SLC7A11, GPX4 and FTH1 expression. However, miR-34a-5p silencing in IR-exo reversed IR-exo-induced ferroptosis in non-irradiated B cells. Moreover, CDKN1A inhibition partially counteracted the suppressive effect of miR-34a-5p knockdown on non-irradiated B cell ferroptosis. Conclusions Our findings suggest that irradiated exosomal miR-34a-5p promotes non-irradiated B cell ferroptosis through CDKN1A, uncovering a novel mechanism for RIBE and offering a new therapeutic target for radioprotection.