Band 19, Heft 1

Prostate cancer (PCa) represents a substantial global health concern and a prominent contributor to male cancer-related mortality. The aim of this study is to explore the role of B-type endothelin receptor (EDNRB) in PCa and evaluate its therapeutic potential. The investigation employed predictive methodologies encompassing data acquisition from the GEO and TCGA databases, gene screening, enrichment analysis, in vitro experiments involving PCR, Western blotting, wound healing, and Transwell assays, as well as animal experiments. Analysis revealed a significant downregulation of EDNRB expression in PCa cells. Overexpression of EDNRB demonstrated inhibitory effects on tumor cell growth, migration, and invasion, likely mediated through activation of the cGMP-Protein Kinase G pathway. In vivo experiments further confirmed the tumor-suppressive properties of EDNRB overexpression. These findings underscore the prospect of EDNRB as a therapeutic target for PCa, offering novel avenues for PCa treatment strategies.

Serine/threonine kinase 11 (STK11), a tumor suppressor gene, exhibits frequent mutations in lung adenocarcinoma (LUAD). However, the specific molecular mechanisms by which STK11 mutations exert an influence on the biosynthesis of monounsaturated fatty acids (MUFAs) and subsequently affect ferroptosis in LUAD remain indistinct. In this study, bioinformatic analysis was employed to probe into the linkage between STK11 and key inhibitory genes of ferroptosis, namely SLC7A11 and SCD1, in LUAD tissues. Quantitative reverse transcription polymerase chain reaction was employed to assess the expression of STK11 in both wild-type and mutant STK11 LUAD cells, cell counting kit-8 to assess cell viability, and flow cytometry to detect apoptosis. A transmission electron microscope was utilized to observe mitochondrial morphology, and Western blot to ascertain the protein expression of STK11, ferroptosis-related proteins, and the enzyme SCD1 involved in MUFA synthesis. Oil red O staining was employed to test the distribution of lipid droplets in cancer cells, and a lipid quantification method to measure the content of MUFAs. Commercial kits were employed to assess the levels of lipid reactive oxygen species, malondialdehyde, glutathione, and Fe 2+ in cells. The result revealed a negative correlation between STK11 and SLC7A11 as well as SCD1, with STK11 expression downregulated in mutant STK11 LUAD cells. Furthermore, STK11 mutations were found to suppress ferroptosis in LUAD cells by affecting MUFA synthesis. Subsequent rescue assays demonstrated that STK11 mutations hindered ferroptosis by impacting the synthesis of MUFAs in LUAD cells. This study provided evidence that STK11 mutations suppressed ferroptosis in LUAD cells by promoting MUFA synthesis, thus offering a novel research direction in the management of LUAD.

Kashin-Beck disease (KBD) is an endemic osteochondropathy. A specific gene called SRY-box transcription factor 6 ( SOX6 ) is important for forming cartilage. This study aims to explore the potential correlation between SOX6 single nucleotide polymorphisms (SNPs) and KBD risk for the first time. In the case–control study, 735 unrelated Chinese Han individuals were enrolled. The four mutation sites of the SOX6 gene (rs4539287 G/A, rs3203295 C/A, rs7928675 C/A, and rs10832681 A/G) were screened and genotyped on the Agena MassARRAY platform. The correlation between SOX6 SNPs and KBD risk was explored based on logistic regression analysis. The interaction between SNP and SNP was analyzed based on the multi-factor dimensionality reduction (MDR) method. Overall analysis revealed a remarkable correlation between rs7928675 and rs10832681 and the reduction of KBD risk ( p < 0.05). Subgroup analyses further indicated that these two SNPs have a significant protective effect on KBD risk among participants aged ≤65 years, males, and non-smokers ( p < 0.05). MDR displayed a marked interaction between rs3203295 and rs10832681. Our study revealed that SOX6 rs7928675 and rs10832681 are markedly correlated with a reduced risk of KBD in the Chinese Han population, providing a new direction for the prevention, diagnosis, and treatment of KBD.

Background Dedifferentiated liposarcoma (DDL), a member of malignant mesenchymal tumors, has a high local recurrence rate and poor prognosis. Pyroptosis, a newly discovered programmed cell death, is tightly connected with the progression and outcome of tumor. Objective The aim of this study was to explore the role of pyroptosis in DDL. Methods We obtained the RNA sequencing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases to identify different pyroptosis-related genes (PRGs) expression pattern. An unsupervised method for clustering based on PRGs was performed. Based on the result of cluster analysis, we researched clinical outcomes and immune microenvironment between clusters. The differentially expressed genes (DEGs) between the two clusters were used to develop a prognosis model by the LASSO Cox regression method, followed by the performance of functional enrichment analysis and single-sample gene set enrichment analysis. All of the above results were validated in the Gene Expression Omnibus (GEO) dataset. Results Forty-one differentially expressed PRGs were found between tumor and normal tissues. A consensus clustering analysis based on PRGs was conducted and classified DDL patients into two clusters. Cluster 2 showed a better outcome, higher immune scores, higher immune cells abundances, and higher expression levels in numerous immune checkpoints. DEGs between clusters were identified. A total of 5 gene signatures was built based on the DEGs and divided all DDL patients of the TCGA cohort into low-risk and high-risk groups. The low-risk group indicates greater inflammatory cell infiltration and better outcome. For external validation, the survival difference and immune landscape between the two risk groups of the GEO cohort were also significant. Receiver operating characteristic curves implied that the risk model could exert its function as an outstanding predictor in predicting DDL patients’ prognoses. Conclusion Our findings revealed the clinical implication and key role in tumor immunity of PRGs in DDL. The risk model is a promising predictive tool that could provide a fundamental basis for future studies and individualized immunotherapy.

Abstracts Overexpression of methyltransferase-like 3 (METTL3) is significantly correlated with the malignancy of lung cancer (LC). In the present study, we demonstrated that METTL3 had higher levels in LC tissues relative to normal tissues. METTL3 showed superior sensitivity and specificity for diagnosis and identification of LC functions. In addition, silencing METTL3 resulted in enhanced ferroptosis sensitivity, whereas overexpression of METTL3 exhibited the opposite effect. Inhibition of METTL3 impeded LC growth in cell-derived xenografts. Further exploratory studies found that METTL3 stimulated the low expression of transferrin receptor (TFRC), which was critical for ferroptosis sensitization in LC cells induced by silenced METTL3, as silencing of TFRC caused a decrease in negative regulators of ferroptosis (FTH1 and FTL) in METTL3 knockdown A549 and PC9 cells. Finally, we confirmed that METTL3 attenuation effectively maintained the stability of TFRC mRNA. In conclusion, we reported a novel mechanism of METTL3 desensitization to ferroptosis via regulating TFRC, and an appropriate reduction of METTL3 might sensitize cancer cells to ferroptosis-based therapy.

Purpose This study identified subtypes and prognostic signature of stage I and stage II gastric cancer based on neutrophil extracellular trap (NET)-related genes. Methods The gene expression data associated with stage I and stage II gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. NET-related genes were obtained from previous reference. Differentially expressed NET-related genes were selected by consensus cluster analysis. The differences in immune infiltration between two subtypes were analyzed. Prognosis-related genes were further screened by univariate Cox regression analysis. Gene Set Enrichment Analysis (GSEA) of prognostic signatures was conducted with clusterprofiler. Finally, a miRNA–mRNA–transcription factor (TF) network was constructed. Results Total 43 differential NET-related genes were obtained and two subtypes were obtained based on these genes. Patients of cluster 2 had a better prognosis compared to cluster 1. Eight types of immune cells were differential in infiltration level between two subtypes. Following univariate Cox regression analysis, two genes of CXC chemokine receptor 4 ( CXCR4 ) and nuclear factor, erythroid 2-like 2 ( NFE2L2 ) significantly related to patient survival were selected. GSEA of single gene revealed that CXCR4 was associated with allograft rejection and NFE2L2 was associated with drug metabolism-cytochrome P450. A network with 421 miRNA–mRNA–TF regulatory pairs was constructed. Conclusion The present study identified two subtypes and a prognostic signature for stage I and stage II gastric cancer based on NET-related genes.

This study aimed to compare the postoperative analgesic efficacy and motor recovery of a novel lumbar plexus block (LPB) with that of a femoral nerve block (FNB) after total knee arthroplasty (TKA). Forty patients who underwent TKA were randomised equally into an lumbar plexus and sciatic nerve (LS) group (receiving novel LPB) and an femoral and sciatic nerves (FS) group (receiving FNB). The assessed variables were the onset time of pain, time to the first analgesic request, pain scores, motor block at 6, 12, and 24 h after TKA, and the number of patients receiving successful blockade for each branch of the lumbar plexus. In the LS group, the femoral, lateral femoral cutaneous, genitofemoral, iliohypogastric, ilioinguinal, and obturator nerves were blocked in 18, 20, 16, 18, 15, and 19 patients. Compared to the FS group, the LS group had a significantly shorter onset time of pain and time to the first analgesic request, a significantly larger total postoperative dose of sufentanil, significantly higher numeric rating scale scores for both rest and dynamic pain at 6, 12, and 24 h, and faster motor recovery. Novel ultrasound-guided LPB has a high blocking success rate and provides inferior postoperative analgesia, but faster motor recovery after TKA than FNB.

This study investigated the relationship between ATP-binding cassette sub-family B member 1 (ABCB1) and OLIG2 single nucleotide polymorphism (SNP) and neurological injury severity and outcome in cerebral infarction (CI). The neurological injury severity of 298 CI patients was evaluated by the National Institutes of Health Stroke Scale. The prognosis of CI patients at 30 days after admission was evaluated by the modified Rankin Scale. And 322 healthy people were selected as the control group. The SNPs of the ABCB1 gene (rs1045642) and OLIG2 gene (rs1059004 and rs9653711) were detected by TaqMan probe PCR, and the distribution of SNPs genotype was analyzed. SNP rs9653711 was correlated with CI. Recessive models of rs1045642 and rs9653711 were correlated with CI. The genotypes of rs1045642 and rs9653711 and genetic models were associated with CI severity. rs1045642 had no correlation with CI prognosis, while rs9653711 had less correlation. The genotype distribution and recessive model were associated with CI prognosis. SNP rs1059004 was not associated with CI severity and prognosis. Alcohol consumption, hypertension, diabetes, hyperlipidemia, and high levels of homocysteine (HCY) were independent risk factors for CI, while hypertension, hyperlipidemia, and HCY were associated with poor prognosis of CI. ABCB1 rs1045642 and OLOG2 rs9653711 are associated with CI severity.

Purpose To compare target area delineation schemes in intensity-modulated radiotherapy (IMRT) effect on patients with locally advanced nasopharyngeal carcinoma (NPC). Methods A total of 88 NPC patients received IMRT and were assigned into control group ( n = 44) and observation group ( n = 44) based on MRI and CT imaging. In the control group, the treatment range was determined as the clinical target volume (CTV) as the gross tumor volume (GTV) + 5 mm. In the observation group, high-risk target areas CTVp1 was GTVp + 5 mm, lymphatic drainage area CTVn1 was GTVn + 5 mm, medium-risk CTVp2 was CTVp1 + 5 mm margin + the whole nasopharyngeal area, CTVn2 was CTVn1 + 5 mm. Radiotherapy treatment course was 6–8 weeks, four times a week. Results The observation group had higher total effective rate, with fewer complications. Neutrophil lymphocyte ratio (NLR), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels were lower after radiotherapy in both groups compared to before radiotherapy, with the observation group demonstrating lower levels than the control group. The effective group exhibited lower serum NLR, IL-6, and TNF-α compared to the non-effective group. T stage, target location, serum NLR, IL-6, and TNF-α were risk factors for the effect of radiotherapy. Conclusions Serum NLR, IL-6, and TNF-α have predictive significance for radiotherapy effect.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a hereditary heart disease characterized by bidirectional or polymorphic ventricular tachycardia and an increased risk of sudden cardiac death. Although trans-2,3-enoyl-CoA reductase like ( TECRL ) is a newly reported pathogenic gene leading to CPVT that can influence intracellular calcium regulation, the unidentified mechanism underlying the pathogenesis of TECRL deficiency-mediated CPVT remains mainly elusive. In the present study, Tecrl knockout (KO) mice were established and the differentially expressed genes (DEGs) were investigated by RNA-sequencing from the heart tissues. In addition, 857 DEGs were identified in Tecrl KO mice. Subsequently, a weighted gene co-expression network analysis was conducted to discern the pivotal pathways implicated in the Tecrl -mediated regulatory network. Moreover, pathway mapping analyses demonstrated that essential metabolism-related pathways were significantly enriched, notably the fatty acid metabolic process and calcium regulation. Collectively, the data suggested a synergistic relationship between Tecrl deficiency and cardiometabolic and calcium regulation during the development of CPVT. Therefore, further studies on the potential function of TECRL in cardiac tissues would be beneficial to elucidate the pathogenesis of CPVT.

Aflatoxin B 1 (AFB 1 ) is a subsidiary poisonous metabolite, archetypally spawned by Aspergillus flavus and A. parasiticus, which are often isolated in warm or tropical countries across the world. AFB 1 is capable of disrupting the functioning of several reproductive endocrine glands by interrupting the enzymes and their substrates that are liable for the synthesis of various hormones in both males and females. In men, AFB 1 is capable of hindering testicular development, testicular degeneration, and reduces reproductive capabilities. In women, a direct antagonistic interaction of AFB 1 with steroid hormone receptors influencing gonadal hormone production of estrogen and progesterone was responsible for AFB 1 -associated infertility. AFB 1 is potentially teratogenic and is responsible for the development of malformation in humans and animals. Soft-tissue anomalies such as internal hydrocephalus, microphthalmia, cardiac defects, augmented liver lobes, reproductive changes, immune modifications, behavioral changes and predisposition of animals and humans to neoplasm development are AFB 1 -associated anomalies. Substances such as esculin, selenium, gynandra extract, vitamins C and E, oltipraz, and CDDO-Im are potential therapies for AFB 1 . Thus, this review elucidates the pivotal pathogenic roles of AFB 1 in infertility, fetal deformities, and potential therapies because AFB 1 toxicity is a key problem globally.

We aimed to investigate the changes in the levels of high-molecular-weight (HMW) adiponectin, adiponectin receptors, and cytokines in patients with chronic obstructive pulmonary disease (COPD), as well as their potential relationships. Forty-one patients who underwent lobectomy for lung lesions and had a clear postoperative pathological diagnosis were divided into the non-COPD ( N = 23) and COPD ( N = 18) groups. HMW adiponectin, cytokine, and T-cadherin levels in serum and tissues were detected by enzyme-linked immunosorbent assay. The levels of HMW adiponectin and cytokine (interleukin [IL]-6, IL-10, surfactant protein D, 4-hydroxynonenal, tumor necrosis factor-α, and C reactive protein) in the serum and tissues increased in the COPD group compared to those in the non-COPD group. Patients with COPD exhibited AdipoR1 upregulation and AdipoR2 downregulation. Although T-cadherin did not differ significantly between patients with and those without COPD, its expression was elevated during the progression from COPD with benign lung lesions to combined lung cancer. Furthermore, the HMW adiponectin levels were significantly correlated with the cytokine levels and the clinical characteristics of COPD. HMW adiponectin and its receptors affect the inflammatory process in COPD and may further contribute to the progression of the disease to malignancy.

Background N6-methyladenosine (m 6 A) is the most frequently occurring interior modification in eukaryotic messenger RNA (mRNA), and abnormal mRNA modifications can affect many biological processes. However, m 6 A’s effect on the metabolism of antiplatelet drugs for the prevention of ischemic stroke (IS) remains largely unclear. Methods We analyzed the m 6 A enzymes and m 6 A methylation in peripheral blood samples of IS patients with/without clopidogrel resistance (CR), and the peripheral blood and liver of rat models with/without CR. We also compared the effect of m 6 A methylation on the expression of the drug-metabolizing enzymes (CYP2C19 and CYP2C6v1) in CR and non-CR samples. Results Methyltransferase-like 3 (METTL3), an m 6 A enzyme, was highly expressed in the peripheral blood of patients with CR, and in both the peripheral blood and liver of rats with CR. This enzyme targets CYP2C19 or CYP2C6v1 mRNA through m 6 A methylation, resulting in low expression of CYP2C19 or CYP2C6v1 mRNA. Consequently, this leads to decreased clopidogrel metabolism and CR. Conclusion The METTL3-mediated methylation of CYP2C19 mRNA may aggravate CR in IS patients.

Advances in lung cancer research applying machine learning (ML) technology have generated many relevant literature. However, there is absence of bibliometric analysis review that aids a comprehensive understanding of this field and its progress. Present article for the first time performed a bibliometric analysis to clarify research status and focus from 2010 to 2021. In the analysis, a total of 2,312 relevant literature were searched and retrieved from the Web of Science Core Collection database. We conducted a bibliometric analysis and further visualization. During that time, exponentially growing annual publication and our model have shown a flourishing research prospect. Annual citation reached the peak in 2017. Researchers from United States and China have produced most of the relevant literature and strongest partnership between them. Medical image analysis and Nature appeared to bring more attention to the public. The computer-aided diagnosis, precision medicine, and survival prediction were the focus of research, reflecting the development trend at that period. ML did make a big difference in lung cancer research in the past decade.

Objective Hospital-acquired pressure ulcers are an important indicator of the quality of care. Most pressure ulcers are avoidable with a robust protocol for prevention, but prevention activities often have a low priority for senior management because the true costs to the hospital are not visible. Our aim was to raise awareness of the value of pressure ulcer prevention by estimating the excess length of inpatient stay associated with hospital-acquired pressure ulcers, and by assessing whether additional costs are covered by increased reimbursement. Methods National activity data for hospitals in Germany are available through the InEK Data Browser. Data were extracted covering discharges from German hospitals between January 1 and December 31, 2021. Cases were selected according to the presence of a pressure ulcer diagnosis using ICD-10-GM codes L89.0–L89.3. Information was extracted for the ten most common German Diagnosis-Related Group (G-DRG) codes in patients with a secondary pressure ulcer diagnosis on mean length of stay and average reimbursement. Ulcer-associated excess length of stay was estimated by comparing cases within the same G-DRG with and without a pressure ulcer diagnosis. Results Mean length of stay was higher in patients with a pressure ulcer than in patients with no ulcer by between 1.9 (all ages) and 2.4 days (patients aged ≥65) per case. In patients aged ≥65 years, 22.1% of cases with a pressure ulcer had a length of stay above the norm for the DRG. In the German system length of stay above the norm is not normally reimbursed. Excess length of stay between 1.9 and 2.4 days leads to a potential cost to a hospital of between 1,633€ and 2,074€ per case. Conclusion Hospital-acquired pressure ulcers represent an important source of cost for a hospital which highlights the potential value of effective prevention.

This study investigated how Metformin (Met) combined with L -carnitine (L-car) modulates brown adipose tissue (BAT) to affect obesity. High-fat-induced obese rats received daily oral gavage with Met and/or L-car, followed by serum biochemical analysis, histopathological observation on adipose tissues, and immunochemistry test for the abdominal expression of BAT-specific uncoupling protein 1 (UCP1). Mouse-embryonic-fibroblast cells were induced into adipocytes, during which Met plus L-car was added with/without saturated fatty acid (SFA). The role of nuclear factor erythroid 2-related factor 2 (Nrf2) in adipocyte browning was investigated by gene silencing. Mitochondria biogenesis in adipocytes was inspected by Mitotracker staining. Nrf2/heme oxygenase-1 (HO-1)/BAT-related genes/proinflammatory marker expressions in adipose tissues and/or adipocytes were analyzed by Western blot, qRT-PCR, and/or immunofluorescence test. Met or L-car improved metabolic disorders, reduced adipocyte vacuolization and swelling, upregulated levels of BAT-related genes including UCP1 and downregulated proinflammatory marker expressions, and activated the Nrf2/HO-1 pathway in adipose tissues of obese rats. Met and L-car functioned more strongly than alone. In adipocytes, Met plus L-car upregulated BAT-related gene levels and protected against SFA-caused inflammation promotion and mitochondria degeneration, which yet was attenuated by Nrf2 silencing. Met plus L-car enhances BAT activity and white adipose tissue browning via the Nrf2/HO-1 pathway to reduce lipid accumulation and inflammation in obese rats.

The purpose of this study was to investigate whether doxorubicin nanobubbles (DOX-NB) combined with diagnostic ultrasound (DUS) irradiation could downregulate the expression of carbonic anhydrase IX (CAIX) in mouse xenograft nasopharyngeal carcinoma (NPC) model. In this study, the prepared DOX-NB was round and well dispersed. The average diameter of DOX-NB was 250.9 ± 50.8 nm, with an average polydispersity of 0.321 ± 0.05. The cumulative release of DOX in the DOX-NB + DUS group was significantly higher compared with that of the DOX-NB group ( p < 0.05). DOX-NB combined with DUS irradiation could significantly inhibit cell viability ( p < 0.05). The expression of CAIX and microvessel density (MVD) in the xenografted tumors was the lowest in the DOX-NB + DUS group compared with that of other groups ( p < 0.05). In conclusion, DOX-NB combined with DUS irradiation could improve DOX-NB drug release and synergistically inhibit NPC cell activity. DOX-NB combined with DUS irradiation can downregulate the expression of CAIX in mouse xenograft NPC model. This may be due to the synergistic effect of DUS combined with DOX-NB in reducing MVD in NPC.

In the study of TAVR, 3-dimensional (3D) printed aortic root models and pulsatile simulators were used for simulation training and teaching before procedures. The study was carried out in the following three parts: (1) experts were selected and equally divided into the 3D-printed simulation group and the non-3D-printed simulation group to conduct four times of TAVR, respectively; (2) another 10 experts and 10 young proceduralists were selected to accomplish three times of TAVR simulations; (3) overall, all the doctors were organized to complete a specific questionnaire, to evaluate the training and teaching effect of 3D printed simulations. For the 3D-printed simulation group, six proceduralists had a less crossing-valve time (8.3 ± 2.1 min vs 11.8 ± 2.7 min, P < 0.001) and total operation time (102.7 ± 15.3 min vs 137.7 ± 15.4 min, P < 0.001). In addition, the results showed that the median crossing-valve time and the total time required were significantly reduced in both the expert group and the young proceduralist group (all P <0.001). The results of the questionnaire showed that 3D-printed simulation training could enhance the understanding of anatomical structure and improve technical skills. Overall, cardiovascular 3D printing may play an important role in assisting TAVR, which can shorten the operation time and reduce potential complications.

Previous studies have found that miR-335 is highly expressed in type II diabetes mellitus (T2DM) models and is related to insulin secretion, but there are few studies on the regulatory effects of miR-335-3p on insulin resistance and macrophage polarization in T2DM patients. This study aims to explore the effects of miR-335-3p on insulin resistance and macrophage polarization in T2DM patients. Blood glucose (insulin tolerance tests, glucose tolerance tests) and body weight of the T2DM model were measured; macrophages from adipose tissue were isolated and cultured, and the number of macrophages was detected by F4/80 immunofluorescence assay; the Real-time quantitative polymerase chain reaction (qPCR) assay and Western blot assay were used to detect the miR-335-3p expression levels, insulin-like growth factor 1 (IGF-1), M1-polarizing genes (inducible nitric oxide synthase [iNOS] and TNF-α) as well as M2-polarizing genes (IL-10 and ARG-1). The targeting link between miR-335-3p and IGF-1 was confirmed using bioinformatics and dual luciferase assay. The results showed that miR-335-3p expression level in adipose tissue of the T2DM model was significantly decreased, and the mice’s body weight and blood glucose levels dropped considerably, miR-335-3p inhibited the number of macrophages, inhibiting the iNOS and TNF-α relative mRNA expression levels, and up-regulated the IL-10 and ARG-1 relative mRNA expression levels, miR-335-3p negatively regulated target gene IGF-1, IGF-1 significantly increased the iNOS and TNF-α mRNA and protein expression levels, decreasing the IL-10 and ARG-1 mRNA and protein expression levels, indicating that miR-335-3p could affect the T2DM process by regulating macrophage polarization via IGF-1.

Causal mutations in the MCPH1 gene have been associated with disorders like microcephaly, and recently congenital hearing impairment. This study examined the MCPH1 DNA repair machinery and identified genetic variations of interest in gnomAD database to discuss the biological roles and effects of rare variants in MCPH1-related diseases. Notably, MCPH1 coordinates two of the seven known mechanisms of DNA repair which confirmed its roles in neurogenesis and chromatin condensation. A pathogenic missense variant in MCPH1 p.Gly753Arg, and two pathogenic frameshifts MCPH1 p.Asn189LysfsTer15 and p.Cys624Ter identified in this study, already had entries in ClinVar and were associated with microcephaly. A pathogenic frameshift in MCPH1 p.Val10SerfsTer5 with a loss-of-function flag and a pathogenic stop gained p.Ser571Ter variants with ultra-rare allele frequency (MAF ≤ 0.001) were identified but have not been linked to any phenotype. The predicted pathogenic ultra-rare variants identified in this study, warranty phenotypic discovery, and also positioned these variants or nearby deleterious variants candidate for screening in MCPH1-associated rare diseases.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro . Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

Pancreatic adenocarcinoma (PAAD) is a prevalent and aggressive malignancy in the digestive tract, requiring accurate prediction and effective treatment strategies. Recently, the discovery of disulfidptosis, a novel form of programmed cell death characterized by abnormal disulfide accumulation, has sparked interest in its role in PAAD. In this study, we aimed to investigate the involvement of disulfidptosis-related genes (DRGs) in PAAD. Using publicly available databases, we conducted a comprehensive analysis exploring the complex relationships between DRGs and important aspects of PAAD, including gene expression, immune response, mutation, drug sensitivity, and functional enrichment. Notably, we observed significant heterogeneity among different disulfidptosis subclusters and identified specific differentially expressed genes in PAAD. Through machine learning techniques, we identified SLC7A11, S100A4, DIAPH3, PRDX1, and SLC7A7 as the most relevant hub genes. We further validated their significance in PAAD by considering their expression patterns, prognostic value, diagnostic potential, diagnostic model, and immune infiltration. This study presents exciting opportunities and challenges in unraveling the underlying mechanisms of PAAD prognosis. It also establishes a foundation for personalized cancer care and the development of innovative immunotherapeutic strategies. By shedding light on the role of DRGs, particularly hub genes, we enhance our understanding and management of PAAD.

This study aimed to investigate the changes of serum carbohydrate antigen 125 (CA125) and prostaglandin E2 (PGE2) in patients with adenomyosis before and after treatment with high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist (GnRH-a). One hundred and sixty-five patients with adenomyosis who received HIFU combined with GnRH-a were selected as case group. Sixty-five healthy women who underwent physical examination at the same time were taken as normal control group. At the end of follow-up 6 months after treatment, the case group were divided into effective subgroup and ineffective subgroup according to clinical efficacy. Changes of serum CA125 and PGE2 were analyzed. Serum CA125 and PGE2 levels in the case group were higher than those in the normal control group before treatment (both P < 0.001). Serum CA125 and PGE2 levels in the case group 6 months after treatment were lower than those before treatment (both P < 0.001). There was no difference in serum CA125 and PGE2 levels between effective subgroup and ineffective subgroup before treatment ( P = 0.351, 0.284, respectively). Serum CA125 and PGE2 levels in the effective subgroup were lower than those in the ineffective subgroup 6 months after treatment (both P < 0.001). Serum CA125 and PGE2 may be involved in the development of adenomyosis, and their expression levels may be related to the prognosis of patients. Levels of serum CA125 and PGE2 in patients with adenomyosis decrease after treatment with HIFU combined with GnRH-a. The detection of serum CA125 and PGE2 may be used as an index to diagnose adenomyosis and evaluate the therapeutic effect of HIFU combined with GnRH-a.

The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed. Statistical analysis comprised univariable/multivariable Cox/logistic regression to identify risk factors of reduced OS/TTR or 90-day post-resection complications and Kaplan–Meier estimator, log-rank, chi-squared, Fisher's exact, and Mann–Whitney U test, or Student's t -test for survival/subgroup analysis. The median HPVG was 6 (range: 0–14) mmHg. The HVPG was an independent risk factor for poorer TTR in the overall cohort (cut-off: ≥7.5 mmHg (17.18/43.81 months; P = 0.009)). In the subgroup analysis of cirrhotic patients ( N = 29 (76%)), HVPG was additionally an independent risk factor for lower OS (cut-off: ≥8.5 mmHg [44.39/76.84 months; P = 0.012]). The HVPG had no impact on OS/TTR in non-cirrhotic patients ( N = 9 (24%)), nor was it associated with postoperative complications in any cohort. In conclusion, preoperative HVPG levels are useful predictors for TTR and OS in cirrhotic HCC patients undergoing hepatic resection.

As there are no predictive models for pulmonary embolism (PE) in patients with suspected PE at cardiology department. This study developed a predictive model for the probability of PE development in these patients. This retrospective analysis evaluated data from 995 patients with suspected PE at the cardiology department from January 2012 to December 2021. Patients were randomly divided into the training and validation cohorts (7:3 ratio). Using least absolute shrinkage and selection operator regression, optimal predictive features were selected, and the model was established using multivariate logistic regression. The features used in the final model included clinical and laboratory factors. A nomogram was developed, and its performance was assessed and validated by discrimination, calibration, and clinical utility. Our predictive model showed that six PE-associated variables (age, pulse, systolic pressure, syncope, D-dimer, and coronary heart disease). The area under the curve – receiver operating characteristic curves of the model were 0.721 and 0.709 (95% confidence interval: 0.676–0.766 and 0.633–0.784), respectively, in both cohorts. We also found good consistency between the predictions and real observations in both cohorts. In decision curve analysis, the numerical model had a good net clinical benefit. This novel model can predict the probability of PE development in patients with suspected PE at cardiology department.

LncRNA XLOC_032768 is reported to prevent renal tubular epithelial cells from cisplatin-induced apoptosis, suggesting its involvement in the development of kidney injury. The present study aimed to explore the role of XLOC_032768 in diabetic nephropathy (DN). The present study enrolled a total of 140 healthy controls (Control group) and 140 patients with type 2 diabetes (Diabetes group). Expression of XLOC_032768 in plasma from these participants was analyzed by performing RT-qPCR. The 140 diabetic patients were followed up for 5 years to monitor the occurrence of diabetic complications. The role of XLOC_032768 in predicting the occurrence of diabetic complications, including DN, diabetic cardiomyopathy (DC), diabetic retinopathy (DR), and diabetic foot (DF) were analyzed by plotting receiver operating characteristic curves and complication-free curves. On the day of admission, plasma levels of XLOC_032768 were not significantly different between Control and Diabetes groups. During follow-up, a total of 22, 15, 13, and 15 cases were diagnosed as DN, DC, DR, and DF, respectively. On the day of diagnosis, plasma levels of XLOC_032768 were only decreased in DN group, but not in other groups, compared to plasma levels of XLOC_032768 on the day of admission. Using plasma levels of XLOC_032768 on the day of admission as a biomarker, potential DN patients were effectively separated from patients with other potential complications and diabetic patients without complications. The 140 diabetic patients were grouped into high and low XLOC_032768 level groups. It was observed that low XLOC_032768 level group showed increased occurrence of DN, but not other complications, compared to high XLOC_032768 level group. Therefore, the downregulation of lncRNA XLOC_032768 in diabetic patients may predict the occurrence of DN.

Circular RNAs (circRNAs) are key regulators of cervical cancer (CC) progression. This study aimed to elucidate the role and mechanism of circ_0051428, a novel circRNA, in CC tumorigenesis. Quantitative real-time polymerase chain reaction and western blotting analyses confirmed that circ_0051428 and matrix metalloprotein-2 (MMP2) were overexpressed in CC, whereas the microRNA miR-885-3p was poorly expressed. After performing a series of in vitro and in vivo experiments, circ_0051428 knockdown was shown to repress CC cell invasion and proliferation in vitro , and hamper tumor formation in vivo . Dual-luciferase reporter and RNA-binding protein immunoprecipitation experiments verified that circ_0051428 interacts with miR-885-3p to regulate the target gene MMP2 of miR-885-3p in CC. In addition, miR-885-3p knockdown offset the anticancer effects of circ_0051428 or MMP2 knockdown on CC cell malignancy. Overall, this study revealed that circ_0051428 executes a tumor-promoting function in CC pathogenesis by modulating the miR-885-3p/MMP2 axis. Our findings provide a novel approach for CC treatment.

Objective To explore the efficacy of ginkgo diterpene lactone (GDLM) on cognitive function in patients with acute ischemic stroke (AIS). Methods A total of 126 patients with AIS in Shaanxi Provincial People’s Hospital from July 2019 to December 2020 were collected and randomly divided into the control group and treatment group ( n = 63). All patients received conventional treatment, on which 25 mg/day GDLM was administered in the treatment group. Coagulation and inflammation indexes, National Institutes of Health Stroke Scale (NIHSS) and activities of daily living scale (ADL) scores were measured before and 14 days after treatment. NIHSS and ADL scores were performed again after 3 months. Cognitive function was assessed by Montréal Cognitive Assessment (MoCA) score, Mini-Mental State Examination (MMSE) score, and potential P300. Results After 14 days of treatment, all biochemical indices were lower than before treatment ( P < 0.05). The NIHSS and ADL scores of the treatment group were significantly better than those of the control group after treatment ( P < 0.05). The MoCA and MMSE scores of the treatment group improved more significantly compared with the control group ( P < 0.05). After treatment, the P300 indexes of both groups were significantly better than before treatment ( P < 0.05). Conclusion Conventional treatment of AIS combined with GDLM can effectively improve the cognitive function of patients, which is worthy of clinical recommendation.

Backgrounds Glioma is a highly malignant brain tumor with a grim prognosis. Genetic factors play a role in glioma development. While some susceptibility loci associated with glioma have been identified, the risk loci associated with prognosis have received less attention. This study aims to identify risk loci associated with glioma prognosis and establish a prognostic prediction model for glioma patients in the Chinese Han population. Methods A genome-wide association study (GWAS) was conducted to identify risk loci in 484 adult patients with glioma. Cox regression analysis was performed to assess the association between GWAS-risk loci and overall survival as well as progression-free survival in glioma. The prognostic model was constructed using LASSO Cox regression analysis and multivariate Cox regression analysis. The nomogram model was constructed based on the single nucleotide polymorphism (SNP) classifier and clinical indicators, enabling the prediction of survival rates at 1-year, 2-year, and 3-year intervals. Additionally, the receiver operator characteristic (ROC) curve was employed to evaluate the prediction value of the nomogram. Finally, functional enrichment and tumor-infiltrating immune analyses were conducted to examine the biological functions of the associated genes. Results Our study found suggestive evidence that a total of 57 SNPs were correlated with glioma prognosis ( p < 5 × 10 −5 ). Subsequently, we identified 25 SNPs with the most significant impact on glioma prognosis and developed a prognostic model based on these SNPs. The 25 SNP-based classifier and clinical factors (including age, gender, surgery, and chemotherapy) were identified as independent prognostic risk factors. Subsequently, we constructed a prognostic nomogram based on independent prognostic factors to predict individualized survival. ROC analyses further showed that the prediction accuracy of the nomogram (AUC = 0.956) comprising the 25 SNP-based classifier and clinical factors was significantly superior to that of each individual variable. Conclusion We identified a SNP classifier and clinical indicators that can predict the prognosis of glioma patients and established a prognostic prediction model in the Chinese Han population. This study offers valuable insights for clinical practice, enabling improved evaluation of patients’ prognosis and informing treatment options.

Introduction Although the correlation between childhood obesity and coronavirus disease 2019 (COVID-19) has been explored, the causality of these remains uncertain. Thus, we conducted a two-sample Mendelian randomization (MR) analysis to identify the causal association. Methods Instrumental variables of childhood obesity were selected from genome-wide association study involving 61,111 Europeans. Besides, we collected summary statistics of different COVID-19 outcomes (susceptibility, hospitalization, and severity) from genome-wide association study including more than 2 million Europeans. The inverse-variance weighted was applied to assess the causality of childhood obesity with COVID-19. Furthermore, we replicated the above association based on another study. Results Inverse-variance weighted results suggested that childhood obesity promoted the COVID-19 susceptibility but has not been validated in other approaches. For hospitalization and severity of COVID-19, we found that childhood obesity, respectively, increased 30 and 38% risk ( P < 0.001), which were consistent in other MR approaches. Discussion Our study provides evidence for a causal relationship between childhood BMI and COVID-19 which is consistent with previous studies. Though these explanations are biologically plausible, further studies are warranted to elucidate the role of these. Conclusions Our study suggests the potential causal associations of childhood obesity with COVID-19, especially hospitalization and severity of COVID-19.

The effect of the lactate dehydrogenase to albumin ratio (LAR) on the survival of patients with acute heart failure (AHF) is unclear. We aimed to analyze the impact of LAR on survival in patients with AHF. We retrieved eligible patients for our study from the Monitoring in Intensive Care Database III. For each patient in our study, we gathered clinical data and demographic information. We conducted multivariate logistic regression modeling and smooth curve fitting to assess whether the LAR score could be used as an independent indicator for predicting the prognosis of AHF patients. A total of 2,177 patients were extracted from the database. Survivors had an average age of 69.88, whereas nonsurvivors had an average age of 71.95. The survivor group had a mean LAR ratio of 13.44, and the nonsurvivor group had a value of 17.38. LAR and in-hospital mortality had a nearly linear correlation, according to smooth curve fitting ( P < 0.001). According to multivariate logistic regression, the LAR may be an independent risk factor in predicting the prognosis of patients with AHF (odd ratio = 1.09; P < 0.001). The LAR ratio is an independent risk factor associated with increased in-hospital mortality rates in patients with AHF.

Background Lipid metabolism disorders lead to lipotoxicity. The hyperlipidemia-induced early stage of renal injury mainly manifests as podocyte damage. CD36 mediates fatty acid uptake and the subsequent accumulation of toxic lipid metabolites, resulting in podocyte lipotoxicity. Methods Male Sprague-Dawley rats were divided into two groups: the normal control group and the high-fat diet group (HFD). Podocytes were cultured and treated with palmitic acid (PA) and sulfo- N -succinimidyl oleate (SSO). Protein expression was measured by immunofluorescence and western blot analysis. Boron-dipyrromethene staining and Oil Red O staining was used to analyze fatty acid accumulation. Results Podocyte foot process (FP) effacement and marked proteinuria occurred in the HFD group. CD36 protein expression was upregulated in the HFD group and in PA-treated podocytes. PA-treated podocytes showed increased fatty acid accumulation, reactive oxygen species (ROS) production, and actin cytoskeleton rearrangement. However, pretreatment with the CD36 inhibitor SSO decreased lipid accumulation and ROS production and alleviated actin cytoskeleton rearrangement in podocytes. The antioxidant N-acetylcysteine suppressed PA-induced podocyte FP effacement and ROS generation. Conclusions CD36 participated in fatty acid-induced FP effacement in podocytes via oxidative stress, and CD36 inhibitors may be helpful for early treatment of kidney injury.

To evaluate the clinical efficacy of etonogestrel subcutaneous implant (ENG-SCI) with that of the levonorgestrel-releasing intrauterine system (LNG-IUD) for adenomyosis treatment. A prospective randomized cohort study was conducted including 108 patients (50 patients in ENG-SCI group and 58 in the LNG-IUD group) with adenomyosis from January 2019 to July 2021. After 3 months of treatment, both ENG-SCI group and LNG-IUD group showed significant improvement in patients’ visual analog scale, pictorial blood loss assessment chart (PBAC), and uterine volume ( P ＜ 0.05). The uterine volume of patients in LNG-IUD group decreased more significantly than that in the ENG-SCI group since 3 months of treatment. The PBAC score in the LNG-IUD group improved better than that in the ENG-SCI group since 6 months of treatment ( P ＜ 0.05). No significant difference in the occurrence rate of ideal vaginal bleeding patterns and the hemoglobin levels between the two groups was observed. The ENG-SCI group had a higher probability of weight gain and progesterone-related side effects ( P ＜ 0.05). Both ENG-SCI and LNG-IUD were effective in treatment of adenomyosis. However, LNG-IUD had a more significant effect in treating adenomyosis-related dysmenorrhea, excessive menstrual flow, anemia, and uterine enlargement, with relatively fewer side effects.

Nasal septal cartilages (NSCs) and mandibular condyle cartilages (MCCs) are two important cartilages for craniomaxillofacial development. However, the role of FLRT2 in the formation of NSCs and MCCs remains undiscovered. NSCs and MCCs were used for immunocytochemistry staining of collagen II, toluidine blue staining, and alcian blue staining. Quantitative reverse transcription‑PCR and western blot were used to detect mRNA and protein expressions of FLRT2, N-cadherin, collagen II, aggrecan, and SOX9. Cell proliferation of MCCs and NSCs was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell counting kit‑8 assay. Cell migration of MCCs and NSCs was examined by wound healing assay and Transwell. Chondrogenesis of MCCs and NSCs were similar in morphological characteristics, while different in cell proliferation, migration, and extracellular matrix. FLRT2 promotes the proliferation and migration of NSCs. There were up-regulation of N-cadherin and down-regulation of collagen II, aggrecan, and SOX9 in NSC with knock down FLRT2. The current study, as demonstrated by Xie et al., reveals that FLRT2 overexpression in Sprague-Dawley neonatal rats promotes the proliferation and migration of NSCs and MCCs, decreases N-cadherin while increases collagen II, aggrecan, and SOX9 in NSC and MCCs. Altogether, FLRT2 mediates chondrogenesis of NSCs and MCCs.

Background Since the outbreak of COVID-19 in December 2019, countries around the world, including China, have been administering COVID-19 vaccines in response to the pandemic. Our center has observed that treating patients with primary immune thrombocytopenia (ITP) has become more challenging in this context. Methods This study compared the treatment response of 25 de novo ITP patients who had received a COVID-19 vaccination (Group 1) with an equal number of de novo ITP patients randomly selected from the 2 years prior to the COVID-19 pandemic (Group 2) by using the Mann–Whitney U test and Fisher’s exact. Results Patients in both groups had predominantly female gender with similar age and baseline platelet counts. However, on Day 3, the median platelets were 22 and 49 × 10 9 /L, and on Day 7, they were 74 and 159 × 10 9 /L, respectively ( P < 0.05). Compared to Group 2, Group 1 showed a suboptimal short-term response to glucocorticoid monotherapy, with a higher proportion of patients requiring combination therapy with other drugs including intravenous immunoglobulin, thrombopoietin receptor agonists, and rituximab. After subgroup analysis, a significant difference was observed in the proportion of patients requiring second-line therapy between the two groups. Conclusions Our study suggests that COVID-19 vaccination may lead to a lower response rate to first-line treatment in de novo ITP patients. Nevertheless, it is crucial to acknowledge the inherent limitations in this conclusion. Further studies are needed to confirm these findings and investigate the underlying mechanisms.

We evaluated the expression profiles of differentially expressed miRNAs (DEmiRNAs) involved in human fetal skin development via high-throughput sequencing to explore the expression difference and the regulatory role of miRNA in different stages of fetal skin development. Analysis of expression profiles of miRNAs involved collecting embryo samples via high-throughput sequencing, then bioinformatics analyses were performed to validate DEmiRNAs. A total of 363 miRNAs were differentially expressed during the early and mid-pregnancy of development, and upregulated DEmiRNAs were mainly concentrated in the let-7 family. The transfection of let-7b-5p slowed down HaCaT cell proliferation and promoted apoptosis, as evidenced by the cell counting kit-8 assay, quantitative real-time polymerase chain reaction, and flow cytometry. The double luciferin reporter assay also confirmed let-7b-5p and ΔNp63 downregulation through the combination with the 3ʹ-untranslated region of ΔNp63. Moreover, treatment with a let-7b-5p inhibitor upregulated ΔNp63 and activated the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway. The let-7b-5p caused a converse effect on HaCaT cells because of Np63 upregulation. Let-7b-5p regulates skin development by targeting ΔNp63 via PI3K-AKT signaling, contributing to future studies on skin development and clinical scar-free healing.

Cardiomyocyte pyroptosis is a primary contributor to sepsis-induced cardiac dysfunction (SICD). Recombinant phospholipid transfer protein (PLTP) have been demonstrated to possess anti-inflammatory and antiseptic properties. However, the effect of PLTP on SICD remains unknown. In this study, we established the in vivo and in vitro sepsis model with the recombinant PLTP treatment. The survival rates of mice, mouse cardiac function, cell viability, the protein level of proinflammatory cytokine, and lactate dehydrogenase level were evaluated. The cardiomyocyte pyroptotic changes were observed. The distribution of PLTP and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in mouse myocardial tissue and expression of PLTP, apoptosis associated speck like protein containing a CARD (ASC), NLRP3, caspase-1, interleukin (IL)-1β, and Gasdermin D (GSDMD) were detected. PLTP ameliorated the cecal ligation and puncture-induced mouse survival rate decrease and cardiac dysfunction, inhibited the IL-1β, IL-18, and tumor necrosis factor (TNF)-α release, and blocked the NLRP3 inflammasome/GSDMD signaling pathway in septic mice. In vitro , PLTP reversed the lipopolysaccharide-induced cardiomyocyte pyroptosis, expression of IL-1β, IL-6, TNF-α, and activation of the NLRP3 inflammasome/GSDMD signal pathway. Moreover, PLTP could bind to NLRP3 and negatively regulate the activity of the NLRP3 inflammasome/GSDMD signal pathway. This study demonstrated that PLTP can ameliorate SICD by inhibiting inflammatory responses and cardiomyocyte pyroptosis by blocking the activation of the NLRP3 inflammasome/GSDMD signaling pathway.

To investigate the impact of goal-directed fluid therapy (GDFT) on postoperative cognitive dysfunction (POCD) in elderly patients with colorectal cancer, we conducted a randomized controlled trial. Eighty elderly patients who underwent elective laparoscopic radical resection of colorectal cancer were randomly assigned to either the GDFT group or the conventional fluid therapy group. The primary outcome was the incidence of POCD during the initial 7 postoperative days, while secondary outcomes included inflammatory marker levels such as interleukin-6 (IL-6) and S100β protein, hemodynamics, level of lactic acid, postoperative functional recovery, and complications. Among 88 randomized patients, 80 were evaluable for the primary outcome. The incidence of POCD was significantly lower in the GDFT group (15.0%) compared to the conventional fluid therapy group (30.0%), with the highest occurrence observed on day 3 postoperatively in both groups ( P < 0.05). IL-6 and S100β concentrations were consistently lower in the GDFT group than in the conventional fluid therapy group at the corresponding time points ( P < 0.05). The GDFT group exhibited more stable perioperative hemodynamics and lower lactate levels ( P < 0.05). Moreover, patients in the GDFT group exhibited better postoperative functional recovery indicators and a lower incidence of postoperative complications ( P < 0.05). In summary, GDFT appears to reduce the incidence of early POCD, accelerate postoperative recovery, and enhance overall prognosis.

In up to 30% patients who experience acute myocardial infarction, successful recanalization of the epicardial coronary artery cannot provide adequate microvascular reperfusion. In this study, we sought to determine whether long-pulsed ultrasound (US)-mediated microbubble (MB) cavitation was useful for the treatment of microvascular obstruction, and the therapeutic effects were compared within different long-pulse-length and short-pulsed US. Microvascular obstruction model was established by injecting micro-thrombi into common iliac artery of a rat’s hind limb. About 1 MHz US with different long pulse lengths (ranging from 100 to 50,000 cycles) was delivered, compared to short pulse (5 cycles). The control group was given MB only without therapeutic US. Contrast perfusion images were performed at baseline, emboli, and 1, 5, 10 min post-embolization, and peak plateau video intensity ( A ) was obtained to evaluate the therapeutic effects. Long-tone-burst US showed better thrombolytic effects than short-pulsed US (1,000, 5,000 cycles >500 cycles, >5 cycles, and control) ( P < 0.01). 1,000 cycles group showed the optimal thrombolytic effect, but microvascular hemorrhage was observed in 50,000 cycles group. In conclusion, long-tone-burst US-enhanced MB therapy mediated successful thrombolysis and may offer a powerful approach for the treatment for microvascular obstruction within a certain pulse length.

The malfunction of SEC61A1 has been linked to several types of cancers, but its role in acute myeloid leukemia (AML) remains poorly understood. In this study, we used a series of bioinformatics analysis techniques, including gene expression profiling and proteomic analysis. Our findings were subsequently validated through a series of in vitro experiments, such as SEC61A1 knockdown in cell lines and RT-qPCR. We discovered a significant up-regulation of SEC61A1 in AML patients compared to healthy controls. AML patients with elevated SEC61A1 expression exhibited reduced overall survival compared to those with lower expression. Moreover, SEC61A1 expression emerged as an independent risk factor for predicting the survival of AML patients undergoing allo-HSCT. Our analysis also revealed an association between high SEC61A1 expression and increased signaling pathways related to cell growth. Our study underscores the importance of SEC61A1 expression as a novel prognostic indicator for predicting survival among AML patients, while also identifying it as a promising therapeutic target.

The limitations of conventional urine culture methods can be avoided by using culture-independent approaches like polymerase chain reaction (PCR) and next-generation sequencing (NGS). However, the efficacy of these approaches in this setting is still subject to contention. PRISMA-compliant searches were performed on MEDLINE/PubMed, EMBASE, Web of Sciences, and the Cochrane Database until March 2023. The included articles compared PCR or NGS to conventional urine culture for the detection of urinary tract infections (UTIs). RevMan performed meta-analysis, and the Cochrane Risk of Bias Assessment Tool assessed study quality. A total of 10 selected studies that involved 1,291 individuals were included in this meta-analysis. The study found that PCR has a 99% sensitivity and a 94% specificity for diagnosing UTIs. Furthermore, NGS was shown to have a sensitivity of 90% for identifying UTIs and a specificity of 86%. The odds ratio (OR) for PCR to detect Gram-positive bacteria is 0.50 (95% confidence interval [CI] 0.41–0.61), while the OR for NGS to detect Gram-negative bacteria is 0.23 [95% CI 0.09–0.59]. UTIs are typically caused by Gram-negative bacteria like Escherichia coli and Gram-positive bacteria like Staphylococci and Streptococci. PCR and NGS are reliable, culture-free molecular diagnostic methods that, despite being expensive, are essential for UTI diagnosis and prevention due to their high sensitivity and specificity.

Renal fibrosis (RF) is an important pathogenesis for renal function deterioration in chronic kidney disease. Secreted frizzled-related protein 5 (SFRP5) is an anti-fibrotic adipokine but its direct role on RF remains unknown. It was aimed to study the protective effect of SFRP5 against RF and interference with Wnt/β‐catenin signaling pathway for the first time. First, the therapeutic efficacy of SFRP5 was evaluated by adenovirus overexpression in rats with unilateral ureteral obstruction (UUO) in vivo . Thirty-six rats were randomly divided into the sham, UUO, and SFRP5 (UUO + Ad-SFRP5) groups. Half rats in each group were selected at random for euthanasia at 7 days and the others until 14 days. Then, the transforming growth factor (TGF)-β1-induced epithelial–mesenchymal transition (EMT) was established in HK-2 cells in vitro . The cells were divided into four groups: the control group, the TGF-β1 group, the TGF-β1 + SFRP5 group, and the TGF-β1 + SFRP5 + anti-SFRP5 group. The makers of EMT and Wnt/β‐catenin pathway proteins were investigated. In the UUO model, expression of SFRP5 showed compensatory upregulation, and adenoviral-mediated SFRP5 over-expression remarkably attenuated RF, as demonstrated by maintenance of E-cadherin and suppression of α-smooth muscle actin (SMA). In vitro , SFRP5 was shown to inhibit TGF-β1-mediated positive regulation of α-SMA, fibronectin, collagen I but negative regulation of E-cadherin. Furthermore, SFRP5 abrogated activation of Wnt/β-catenin, which was the essential pathway in EMT and RF pathogenesis. The changes after a neutralizing antibody to SFRP5 confirmed the specificity of SFRP5 for inhibition. These findings suggest that SFRP5 can directly ameliorate EMT and protect against RF by inhibiting Wnt/β-catenin pathway.

Disulfidptosis was recently reported to be caused by abnormal disulfide accumulation in cells with high SLC7A11 levels subjected to glucose starvation, suggesting that targeting disulfidptosis was a potential strategy for cancer treatment. We analyzed the relationships between gene expression and mutations and prognoses of patients. In addition, the correlation between gene expression and immune cell infiltration was explored. The potential regulatory mechanisms of these genes were assessed by investigating their related signaling pathways involved in cancer, their expression patterns, and their cellular localization. Most cancer types showed a negative correlation between the gene-set variation analysis (GSVA) scores and infiltration of B cells and neutrophils, and a positive correlation between GSVA scores and infiltration of natural killer T and induced regulatory T cells. Single-cell analysis revealed that ACTB , DSTN , and MYL6 were highly expressed in different bladder urothelial carcinoma subtypes, but MYH10 showed a low expression. Immunofluorescence staining showed that actin cytoskeleton proteins were mainly localized in the actin filaments and plasma membrane. Notably, IQGAP1 was localized in the cell junctions. In conclusion, this study provided an overview of disulfidptosis-related actin cytoskeleton genes in pan-cancer. These genes were associated with the survival of patients and might be involved in cancer-related pathways.

This study is to probe into the meaning of serum miR-532-5p in nontraumatic osteonecrosis of the femoral head (ONFH), and a molecular mechanism of miR-532-5p in the development of nontraumatic ONFH. This study enrolled 96 patients diagnosed with nontraumatic ONFH and 96 patients with femoral neck fracture. The levels of miR-532-5p, ABL1, MMP-3, MMP-13, and cleaved-caspase3 were determined. Radiographic progression was assessed by ARCO staging system. Visual analog scale (VAS) and Harris hip score (HHS) were employed for evaluation of the symptomatic severity of nontraumatic ONFH. Cell viability and apoptosis in chondrocytes isolated from clinical samples were investigated with CCK-8 and flow cytometry. The levels of lactic dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), mitochondrial membrane potential (Δ Ψ m), and reactive oxygen species (ROS) were determined. miR-532-5p was downregulated in tissues and serum of patients with nontraumatic ONFH, negatively related with ARCO staging and VAS, and positively correlated with HHS. Cell apoptosis, LDH, MDA, and ROS strengthened, while cell viability, Δ Ψ m, and SOD reduced in chondrocytes of nontraumatic ONFH patients. ABL1 was upregulated in cartilage tissues from nontraumatic ONFH patients. miR-532-5p targeted ABL1, and overexpressed miR-532-5p alleviated nontraumatic ONFH-induced oxidative stress damage of chondrocytes by restraining ABL1. miR-532-5p ameliorated oxidative stress injury in nontraumatic ONFH by inhibiting ABL1.

Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region ( n = 5), intrahepatic cholangiocarcinoma ( n = 3), gallbladder cancer ( n = 1), liver metastasis from colorectal cancer ( n = 1), and liver metastasis from gastrointestinal mesenchymal tumor ( n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13–44) and median open diet was Day 4 (range 2–9) after surgery and median early post-operative activity was Day 5 (range 2–9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.

Uterine rupture is a rupture of the body or lower part of the uterus during pregnancy or delivery. Total of 98 cases with incomplete uterine rupture were classified as the incomplete uterine rupture group, 100 cases with a history of cesarean delivery without uterine rupture were classified as the non-ruptured uterus group, and controls were selected using a systematic sampling method. The maternal age ≥35 years were associated with 2.18 times higher odds of having an incomplete uterine rupture. The odd of having an incomplete uterine rupture was 3.744 times higher for a woman with delivery interval ≤36 months. Having pregnancy complication was associated with 3.961 times higher odds of having an incomplete uterine rupture. The neonatal weight was lighter in the incomplete uterine rupture group ( P = 0.007). The number of preterm birth and transfer to the NICU were higher in the incomplete uterine rupture group ( P ＜ 0.01). The operation time and the length of time in hospital were longer in the group with incomplete uterine rupture ( P ＜ 0.01). Age ≥35 years, delivery interval ≤36 month, and pregnancy with complication were independent risk factors of incomplete rupture of the uterus secondary to previous cesarean section.

Aim Abnormalities in sleep patterns are a common health problem for the older adults. The relationship between sarcopenia and sleep duration in older people is controversial. This research is to examine the association between sleep duration and sarcopenia. Methods We drew 21,095 adults from the China Health and Retirement Longitudinal Survey (CHARLS). Not only we explore the relationship between sleep duration and sarcopenia, but also compare sleep duration to three sarcopenia subcomponents. Moreover, the sensitivity analysis was conducted by the gender and residence area to ascertain the discrepancy, separately. Finally, using restricted cubic spline to find the non-linear association between them. Results Among 7,342 community older adults engaged by CHARLS in 2015, the incidence of possible sarcopenia and sarcopenia was 23.14 and 11.30%, separately. Sleep duration (≤6 h) [OR(95%CI) = 1.30(1.03–1.65), p < 0.05] and (≥8 h) [OR(95%CI) = 1.33(1.05–1.69), p < 0.05] were significantly linked with possible sarcopenia, while long sleep duration (≥8 h) [OR(95%CI) = 1.41(1.01–2.02), p < 0.05] was correlated strongly with sarcopenia. A non-linear relationship (U-shaped) between sarcopenia risk and sleep duration was found ( p for non-linear = 0.009). Conclusions Our findings highlight the importance of sleep duration in the onset of sarcopenia and might assist older persons to maintain good sleeping habits.

Objective: We applied Mendelian randomization to explore the causal relationship between obesity and benign paroxysmal vertigo (BPV). Methods: We chose two types of obesity diseases. Obesity due to excessive calories and other or unspecified obesity from the FinnGen database. We used genomic significance ( p < 5 × 10 −8 ) to obtain independent single nucleotide polymorphisms (SNPs) as instrumental variables. Similarly, genome-wide association study data for the disease BPV were selected from the FinnGen database. R was then used to test the data for multiplicity and heterogeneity, as well as to detect the effect of individual SNPs on the results. Random effects inverse variance weighting was used as the main statistical analysis. Results: First, by analyzing, we found an outlier in obesity due to excessive calories (rs12956821). Outliers were then removed, and the statistical results were analyzed without heterogeneity ( p > 0.05) and horizontal pleiotropy ( p > 0.05), as well as individual SNPs having no effect on the results. Meanwhile, random-effects IVW results showed obesity due to excessive calories ( p = 0.481; OR = 0.941), and other or unspecified obesity ( p = 0.640; OR = 0.964). Conclusions: The present study did not find a causal relationship between the above two obesity types and BPV at the genetic level.

Multiple organs are affected by the complex autoimmune illness known as systemic sclerosis (SSc), which has a high fatality rate. Genes linked to autophagy have been linked to the aetiology of SSc. It is yet unknown, though, whether autophagy-related genes play a role in the aetiology of SSc. After using bioinformatics techniques to examine two databases (the GSE76885 and GSE95065 datasets) and autophagy-related genes, we were able to identify 12 autophagy-related differentially expressed genes that are linked to the pathophysiology of SSc. Additional examination of the receiver operating characteristic curve revealed that SFRP4 (AUC = 0.944, P < 0.001) and CD93 (AUC = 0.904, P < 0.001) might be utilized as trustworthy biomarkers for the diagnosis of SSc. The SSc group’s considerably greater CD93 and SFRP4 expression levels compared to the control group were further confirmed by qRT-PCR results. The autophagy-related genes SFRP4 and CD93 were found to be viable diagnostic indicators in this investigation. Our research sheds light on the processes by which genes linked to autophagy affect the pathophysiology of SSc.

Esophageal squamous cell carcinoma (ESCC), a highly aggressive subtype of esophageal cancer, is characterized by late-stage diagnosis and limited treatment options. Recent advancements in transcriptome sequencing technologies have illuminated the molecular intricacies of ESCC tumors, revealing metabolic reprogramming as a prominent feature. Specifically, the Warburg effect, marked by enhanced glycolysis, has emerged as a hallmark of cancer, offering potential therapeutic targets. In this study, we comprehensively analyzed bulk RNA-seq data from ESCC patients, uncovering elevated SRA1 expression in ESCC development and a poorer prognosis. Silencing of SRA1 led to a modulation of glycolysis-related products and a shift in PKM2 expression. Our findings shed light on the intricate molecular landscape of ESCC, highlighting SRA1 as a potential therapeutic target to disrupt glycolysis-dependent energy production. This metabolic reprogramming may hold the key to innovative treatment strategies for ESCC, ultimately improving patient outcomes.

Schizophrenia is a chronic mental illness with a poor quality of life (QoL). The main aim of this study was to measure the QoL and factors that affect the QoL of patients with schizophrenia placed in a social welfare institution. This cross-sectional study included 287 patients with schizophrenia who were treated in a long-stay social care institution in which QoL was assessed using five different instruments: the World Health Organization Quality of Life scale, the EuroQoL Five-Dimension-Five-Level scale (including the visual analog scale), the Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form, and the Brief Psychiatric Rating Scale. To determine the impact of patients’ characteristics on score values, multiple linear regression using backward elimination was employed. Due to non-normality in the distribution of the dependent variables, a Box–Cox power transformation was applied to each dependent variable prior to conducting multiple linear regression analysis. Results revealed that patients with schizophrenia have lower QoL. Our study revealed that age, level of education, type of accommodation, type of pavilion, age of onset of the disease, number of prescribed antipsychotics, number of psychiatric comorbidities, duration of therapy, and the number of daily doses of antipsychotics are dominant contributors to the QoL in patients with schizophrenia who were treated in social welfare institution.

Oxidative stress markers have a distinct role in the process of demyelination in multiple sclerosis. This study investigated the potential correlation of markers of oxidative stress (glutathione [GSH], catalase) with the number of demyelinating lesions and the degree of disability, cognitive deficit, and depression in patients with relapsing-remitting multiple sclerosis (RRMS). Sixty subjects meeting the criteria for RRMS (19 men and 41 women), and 66 healthy controls (24 men, 42 women) were included. In this study, GSH significantly negatively correlated with the degree of cognitive impairment. This is the first study of subjects with RRMS that performed the mentioned research of serum GSH levels on the degree of cognitive damage examined by the Montreal Scale of Cognitive Assessment (MoCA) test. The development of cognitive changes, verified by the MoCA test, was statistically significantly influenced by the positive number of magnetic resonance lesions, degree of depression, expanded disability status scale (EDSS), age, and GSH values. Based on these results, it can be concluded that it is necessary to monitor cognitive status early in RRMS patients, especially in those with a larger number of demyelinating lesions and a higher EDSS level and in older subjects. Also, the serum level of GSH is a potential biomarker of disease progression, which could be used more widely in RRMS.

Objective The aim of this research was to compile a self-management assessment scale for patients with aortic dissection (AD). The questionnaire is useful in making the patient aware of the need for post-operative care in order to contribute to improving the outcome and quality of life. Methods The initial version of the “postoperative self-management assessment scale for patients with aortic dissection” was developed using the Delphi expert consultation method based on qualitative research results, consultation of self-management-related literature, reference to the existing self-management scale, and self-efficacy theory, combined with the disease characteristics of AD. By using the convenience sampling method, a total of 201 patients with AD who had undergone surgery were selected as the research participants. The initial version of the scale was used for follow-up investigation, and the scale entries were evaluated and exploratory factor analysis carried out to form the formal version of the “postoperative self-management assessment scale for patients with aortic dissection.” A total of 214 patients with AD after surgery were selected as the research participants. The formal version of the scale was used for follow-up investigation, and its reliability and validity were evaluated. Results The formal version of the scale had 6 dimensions and 35 entries. The Cronbach’s α coefficient for the total scale was 0.908, the split-half reliability was 0.790, and the test–retest reliability after 2 weeks was 0.471. The content validity index of the total scale was 0.963. Exploratory factor analysis yielded six common factors, and the cumulative contribution rate of variance was 66.303%. Confirmatory factor analysis showed that except for the incremental fit index, Tucker–Lewis index, and comparative fit index >0.85, slightly lower than 0.90, χ 2 /df <3, root mean square of approximation <0.08, parsimonious goodness-of-fit index, and parsimonious normed fit index >0.50; all other model fitting requirements were satisfied, indicating that the model fitting was acceptable. Conclusion We compiled the postoperative self-management assessment scale for patients with AD, which has demonstrated excellent reliability and validity and can be used as a tool to evaluate the postoperative self-management level in patients with aortic dissection.

Objective In the present study, we investigated the impact of left atrial appendage closure (LAAC) following catheter ablation (CA) on the left atrial structure and functioning of patients with paroxysmal atrial fibrillation (AF). Methods Patients with paroxysmal AF were enrolled in this single-center prospective cohort study between April 2015 and July 2021; 353 patients received CA alone, while 93 patients received CA in combination with Watchman LAAC. We used age, gender, CHA2DS2-VASc, and HAS-BLED scores as well as other demographic variables to perform propensity score matching. Patients with paroxysmal AF were randomly assigned to the CA combined with Watchman LAAC group (combined treatment group) and the simple CA group, with 89 patients in each group. The left atrial structure, reserve, ventricular diastole, and pump functions and their changes in patients were assessed using routine Doppler echocardiography and 2D speckle tracking echocardiography over the course of a 1-year follow-up. Results At 1-week follow-up, the reserve, ventricular diastole, and pump functions of the left atrium (LA) increased in both groups; these functions were gradually restored at the 1- to 3-month follow-up; they were close to or returned to their pre-operative levels at the 3-month follow-up; and no significant differences were found compared with the pre-operative levels at the 12-month follow-up. In the first 3 months, the reserve (Ƹ, SRs) and pump functions (SRa) in the combined treatment group decreased significantly when compared with the simple CA group, and the differences were statistically significant. Conclusion Patients with paroxysmal AF may experience a short term, partial effect of LAAC on LA reserve and pump functions, which are gradually restored and the effect disappears by 12 months.

Purpose To explore the effect of AFN on knee function and complications in patients after TKA. Methods We evaluated 150 patients undergoing unilateral TKA, specifically including 102 patients with varying degrees of AFN after selection. They were divided into four groups based on AFN grade. About 48 patients did not produce AFN, 63 patients were grade I, 29 patients were grade II, and 10 patients were grade III. All patients were followed up for 24 months, and knee function, pain, complications, and other indicators were compared between the four groups. Correlation analysis and regression analysis were used to study the relationship between AFN and other indicators. Results Two cases of periprosthetic fractures (PPF) occurred in our study, with an incidence of 1.35%, which did not show a significant association with AFN. The changes in knee social score (ΔKSS), Western Ontario and McMaster Universities Osteoarthritis Index (ΔWOMAC), and postoperative anterior knee pain visual analog scale (VAS) score were higher in patients with AFN than in those without. Particularly, grades II and III AFN demonstrated superior efficacy. Pearson’s correlation analysis showed that AFN grade is positively correlated with both ΔKSS and ΔWOMAC ( r = 0.44, P < 0.001), and AFN grade had a negative correlation with the anterior knee pain VAS ( r = −0.250, P < 0.05). In linear regression analysis, AFN grade was positively correlated with both ΔKSS ( β = 5.974, 95% CI: 3.968–7.981, P < 0.001) and ΔWOMAC ( β = 6.356, 95% CI: 4.223–8.490, P < 0.001). Besides that, there was a negative correlation between AFN grade and anterior knee pain ( β = 5.974, 95% CI: 3.968–7.981, P < 0.05). Conclusion Patients with grade II and III AFN who underwent TKA exhibited better knee function and lower levels of anterior knee pain post-surgery.

Purpose The aim of this study is to describe the novel epidemiological and clinical characteristics of influenza A-induced severe pneumonia occurring after the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to further assess its potential risk factors for mortality. Methods We retrospectively studied the consecutive case series of 30 patients with confirmed influenza A-induced severe pneumonia treated in the intensive care unit at Dazhou Central Hospital in Sichuan, China, from March 1 to April 30, 2023. Logistic regression was used to analyze the independent risk factors, and receiver operating characteristic (ROC) curves were applied to evaluate the predictive efficacy of associated risk factors for mortality. Results The mortality rate was 33.3% in this study. Independent risk factors for mortality of patients were acute respiratory distress syndrome (ARDS) ( p = 0.044) and septic shock ( p = 0.012). ROC statistics for ARDS and septic shock to predict mortality in patients with influenza A-induced severe pneumonia demonstrated an area under the curve of 0.800 (sensitivity 80.0%, specificity 80.0%) and 0.825 (sensitivity 70.0%, specificity 95.0%), respectively. Conclusion ARDS and septic shock were the independent risk factors for mortality in patients with influenza A-induced severe pneumonia following the end of the SARS-CoV-2 pandemic. But high level of next generation sequencing reads Aspergillus coinfection, and comorbidities did not increase death risk of the study population.

Objective This study aimed to investigate whether analgesia nociception index (ANI) could be an indicator of perioperative pain during laparoscopic trocar insertion. Methods A total of 280 participants of anesthesia receiving laparoscopic surgery were enrolled. Anesthesia induction and maintenance were performed using the Marsh model for target propofol and the Minto model for remifentanil. Systolic blood pressure (SBP), heart rate (HR), and ANI were recorded at skin incision, the first-, second, the last-trocar insertion, and 5 min after the last trocar insertion. Results ANI was significantly different among the five groups in the last four time points (all P < 0.05). Pearson’s correlation showed that ANI was negatively correlated with SBP ( r = −0.114, P = 0.077) and HR ( r = −0.247, P < 0.001). The area under the curve of ANI was positively correlated with those of SBP ( r = 0.493, P < 0.001) and HR ( r = −0.420, P < 0.001). Multivariate logistic regression showed that the ANI was an independent factor associated with intraoperative hemodynamic adverse events only at 5 min after the last trocar insertion. Conclusions Under general anesthesia, the change in ANI was consistent with changes in the balance between analgesia and nociceptive stimuli. The ANI can reflect the extent of transient pain but had a poor predictive performance for hemodynamic adverse events.

The aim of our study is to explore the mechanism of transcription-4 (STAT4) in acute myeloid leukemia (AML). STAT4 level in AML bone marrow samples/cells was analyzed using bioinformatics and quantitative real-time PCR. The correlation between high STAT4 expression and the prognosis of AML patients was analyzed. The viability, apoptosis, and angiogenesis of AML cells were detected. The levels of STAT4, vascular endothelial growth factor A (VEGFA), and apoptosis-related proteins (Bcl-2 and Bax) in transfected AML cells were examined. STAT4 level was upregulated in AML. STAT4 silencing decreased the viability and angiogenesis, yet increased the apoptosis of AML cells, while overexpressed STAT4 did conversely. VEGFA silencing counteracted the impacts of overexpressed STAT4 upon promoting viability and angiogenesis as well as repressing the apoptosis of AML cells. High STAT4 expression was correlated with poor prognosis of AML patients and facilitated disease progression via upregulating VEGFA expression.

Background COVID-19 sequelae are long-term symptoms of COVID-19. Cardiovascular disease is not only a risk factor for the occurrence of COVID-19 sequelae but also a potential result directly or indirectly caused by COVID-19 infection. Objectives The aim of this study is to investigate the cardiovascular system-related symptoms of outpatients and inpatients of the Cardiovascular Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine after recovery from novel coronavirus infection, analyze the influencing factors, and symptom characteristics of related symptoms, and thereby provide a basis for further formulating a reasonable diagnosis and treatment plan. Materials and methods From January 15, 2023 to February 15, 2023, 452 recovered patients with novel coronavirus infection who were admitted to the Cardiovascular Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine due to symptoms of the cardiovascular system (complaints of chest pain and palpitations) were involved in this study. A unified questionnaire was used to record the general information, past medical history, characteristics of chest pain or palpitations, and other COVID-19-related sequelae of the selected patients. All data were statistically analyzed by SPSS 26.0 statistical software. Results A total of 226 patients with cardiovascular symptoms and 226 patients without cardiovascular symptoms were included in this study. After univariate and multivariate logistic regression analysis, women (OR 2.081, 95% CI = 1.358–3.189) and young people (OR 2.557, 95% CI = 1.44–4.54) had a higher risk of cardiovascular symptoms; prehypertension (OR 1.905, 95% CI = 1.091–3.329) and hypertension (OR 2.287, 95% CI = 1.433–3.649) increased the risk of cardiovascular symptoms; patients with history of previous cardiovascular disease (OR 1.862, 95% CI = 1.16–2.988) and history of diabetes (OR 2.138, 95% CI = 1.058–4.319) had a higher risk of developing cardiovascular symptoms. The main symptoms related to COVID-19 sequelae reported by all 452 patients were fatigue (76.8%), shortness of breath (54.2%), dry mouth and bitter mouth (46.0%), gastrointestinal symptoms (42.7%), sleep disturbances (37.4%), sweating (31.9%), chills (29%), dizziness (25.7%), confusion of brain fog (25.2%), and tinnitus (14.6%). Compared with patients without cardiovascular symptoms, patients with cardiovascular symptoms were more likely to have shortness of breath (OR 3.521, 95% CI = 2.226–5.472), gastrointestinal symptoms (OR 2.039, 95% CI = 1.226–3.393), and dry mouth and bitter mouth (OR 1.918, 95% CI = 1.229–2.992). The differences were statistically significant ( P < 0.05). Conclusion In this new coronavirus infection, women, young people, the elderly, people with prehypertension, hypertension, and patients with a history of cardiovascular disease and diabetes have a higher risk of developing cardiovascular symptoms, and patients with cardiovascular symptoms are more likely to develop other COVID-19 sequelae.

Ulcerative colitis (UC) has been identified as a severe inflammatory disease with significantly increased incidence across the world. The detailed role and mechanism of HOXD10 in UC remain unclear. In present study, we found that HOXD10 was lowly expressed in UC samples and was notably decreased by dextran sulfate sodium (DSS) administration. Overexpression of HOXD10 dramatically ameliorated DSS-induced UC symptoms, including the loss of weight, increased disease activity index values, and the shortened colon length. Additionally, terminal-deoxynucleoitidyl transferase mediated nick end labeling and immunohistochemistry staining assays showed that HOXD10 overexpression suppressed cell apoptosis and facilitated proliferation of colon tissues after DSS treatment. Moreover, HOXD10 overexpression obviously suppressed DSS-triggered inflammatory response by decreasing the expression level of TNF-α, IL-6, and IL-1β. Furthermore, overexpression of HOXD10 effectively restored the intestinal permeability, thereby alleviating DSS-induced intestinal barrier dysfunction. Mechanistic study demonstrated that HOXD10 significantly reduced the activities of Rho/ROCK/MMPs axis in colon tissues of mice with UC. In conclusion, this study revealed that HOXD10 might effectively improve DSS-induced UC symptoms by suppressing the activation of Rho/ROCK/MMPs pathway.

Liver fibrosis is a key contributor to hepatic disease-related mortality. Exosomes derived from mesenchymal stem cells (MSCs) have been revealed to improve liver fibrosis. To explore the effect and mechanism of MSC-derived exosomal miR-26a on liver fibrosis, exosomes were separated from bone marrow-derived MSCs (BMSCs) and used to treat with LX2 cells. The miR-26a level was decreased in BMSC-derived exosomes. Treatment with exosomes isolated from human BMSCs transfected with miR-26a mimics (miR-26a mimic-Exo) decreased the 5-ethynyl-2'-deoxyuridine-positive cell rate, the protein level of α-SMA and collagen I, and the glutathione (GSH) level but enhanced the apoptosis rate and the reactive oxide species (ROS) level in LX2 cells, which were reversed by the treatment of deferoxamine. Mechanically, miR-26a directly bound SLC7A11 mRNA and negatively modulated the level of SLC7A11 in LX2 cells. Overexpression of SLC7A11 reversed the miR-26a mimic-Exo-induced alterations in the level of ROS, Fe 2+ , malonaldehyde, and GSH in LX2 cells. In vivo , miR-26a mimic-Exo decreased the level of SLC7A11 and attenuated CCL4-induced liver fibrosis. Collectively, miR-26a mimic-Exo induced ferroptosis to alleviate liver fibrosis by regulating SLC7A11, which may provide new strategies for the treatment of liver fibrosis, and even other relevant diseases.

Introduction In the absence of clinical trials, the benefit of endovascular therapy (EVT) on the treatment of acute ischemic stroke (AIS) with primary distal and medium vessel occlusions (DMVO) is still not well defined. The aim of the study is to evaluate EVT with or without intravenous thrombolysis (EVT ± IVT) in primary DMVO stroke in comparison with a control cohort treated with IVT alone. Methods We analysed all consecutive AIS with proven primary DMVO. Primary endpoints were excellent outcome, functional independence at 3 months follow-up, and early neurologic improvement at 1 day after treatment. Results One hundred and fourteen patients with DMVO strokes were included between 2019 and 2023. Propensity-weighted analysis showed no significant differences in EVT ± IVT vs IVT for the excellent outcome (adjusted OR [aOR], 1.575; 95% CI, 0.706–3.513), functional independence (aOR, 2.024; 95% CI, 0.845–4.848), early neurological improvement (aOR, 2.218; 95% CI, 0.937–5.247), mortality (aOR, 0.498; 95% CI, 0.177–1.406), symptomatic intracranial haemorrhage (aOR, 0.493; 95% CI, 0.102–2.385), and subarachnoid haemorrhage (aOR, 0.560; 95% CI, 0.143–2.187). The type of revascularization did not influence the percentage of cerebral volume lost (adjusted linear regression estimate, −19.171, t value, 11.562; p = 0.104). Conclusions This study supports the hypothesis that patients with primary DMVO stroke treated with EVT (±IVT) or IVT alone have comparable outcomes.

Herein, we elucidate the potential role of ANO6 (TMEM16F) in gastrointestinal stromal tumors (GISTs). ANO6 expression in GIST and adjacent normal tissues was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell proliferation, apoptosis, and pyroptosis were examined utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, terminal deoxynucleotidyl transferase dUTP Nick-End Labeling staining, and flow cytometry. In addition, the total iron and Fe 2+ levels were assessed. IL-18 and IL-1β levels were also evaluated. Lipid reactive oxygen species (ROS), cystine (Cys), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels were evaluated using appropriate kits. Ferroptotic markers, including Ptgs2 , Chac1 , SLC7A11 , and SLC3A2 , were analyzed by RT-qPCR, western blotting, and immunohistochemistry. ANO6 expression decreased in GIST tissues. ANO6 -plasmid inhibits proliferation, induces apoptosis, and promotes pyroptosis in GIST-T1 and GIST-T1 IR cells. The ANO6 -plasmid induced ferroptosis, as confirmed by enhanced lipid ROS levels, increased intracellular concentrations of total iron and Fe 2+ , promoted Ptgs2 and Chac1 expression, reduced Cys, GSH, and GPX4 levels, and downregulated SLC7A11 and SLC3A2 expression after in vitro and in vivo treatment with ANO6 -plasmid. Moreover, the ANO6 -plasmid inhibited GIST growth in vivo . Therefore, ANO6 may be a promising therapeutic target for blocking the development of GIST via the induction of apoptosis, pyroptosis, and ferroptosis.

Aims In cancer biology, the aberrant overexpression of eukaryotic translation initiation factor 5A2 (EIF5A2) has been correlative with an ominous prognosis, thereby underscoring its pivotal role in fostering metastatic progression. Consequently, EIF5A2 has garnered significant attention as a compelling prognostic biomarker for various malignancies. Our research endeavors were thus aimed at elucidating the utility and significance of EIF5A2 as a robust indicator of cancer outcome prediction. Method An exhaustive search of the PubMed, EMBASE, and Web of Science databases found relevant studies. The link between EIF5A2 and survival prognosis was examined using hazard ratios and 95% confidence intervals. Subsequently, The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases were employed to validate EIF5A2 expression across various cancer types. Results Through pooled analysis, we found that increased EIF5A2 expression was significantly associated with decreased overall survival (OS) and disease-free survival/progression-free survival/relapse-free survival (DFS/PFS/RFS). Moreover, TCGA analysis revealed that EIF5A2 was significantly upregulated in 27 types of cancer, with overexpression being linked to shorter OS in three, worse DFS in two, and worse PFS in six types of cancer. GEPIA showed that patients with EIF5A2 overexpression had reduced OS and DFS. Conclusions In solid tumors, EIF5A2 emerges as a reliable prognostic marker. Our meta-analysis comprehensively analyzed the prognostic value of EIF5A2 in solid tumors and assessed its efficacy as a predictive marker.

The pathogenesis of ulcerative colitis (UC) involves chronic inflammation of the submucosal layer and disruption of epithelial barrier function within the gastrointestinal tract. Connexin 43 (Cx43) has been implicated in the pathogenesis of intestinal inflammation and its associated carcinogenic effects. However, a comprehensive analysis of Cx43’s role in mucosal and peripheral immunity in patients with UC is lacking. In this study, the colon tissues of patients with UC exhibited severe damage to the intestinal mucosal barrier, resulting in a significant impairment of junctional communication as observed by transmission electron microscopy. The mRNA expression of Cx43 was found to be significantly elevated in the UC group compared to the control group, as determined using the Affymetrix expression profile chip and subsequently validated using qRT-PCR. The immunofluorescence analysis revealed a significantly higher mean fluorescence intensity of Cx43 in the UC group compared to the control group. Additionally, Cx43 was observed in both the cell membrane and nucleus, providing clear evidence of nuclear translocation. The proportion of Cx43 in the UC group for CD4 + and CD8 + T lymphocytes was increased in the control group, but only the proportion of Cx43 for CD8 + T lymphocytes showed significant difference by flow cytometry. The involvement of Cx43 in the pathogenesis of UC and its potential role in mucosal immunity warrants further investigation, as it holds promise as a prospective biomarker and therapeutic target for this condition. The proportion of Cx43 in the UC group for CD4 + and CD8 + T lymphocytes was increased in the control group, but only the proportion of Cx43 for CD8 + T lymphocytes showed a significant difference.

Background The occurrence of COVID-19 led to the rapid development of several vaccines which were distributed around the world. Even though there had been a vast amount of information about both virus and vaccination, this process was potentially related to increased anxiety and thus affected the vaccination process. Objective The present study examined anxiety levels and body vigilance in subjects reporting for COVID-19 vaccination at different vaccination sites. Methods Instruments used included general socio-demographic questionnaires and specifically constructed ones such as generalized anxiety disorder (GAD), body vigilance scale (BVS), and coronavirus anxiety scale (CAS). Results A total of 227 subjects enrolled in the study reported mild GAD and CAS scores and relatively low scores on BVS. When the subjects were divided according to a vaccination site (under supervision and non-supervised), it turned out that subjects vaccinated under supervision were more anxious (higher GAD and CAS) and had their body vigilance increased. Conclusion In conclusion, there is a need for highlighting the importance of efficient planning and organization of vaccination process, since to a certain extent it is driven by both anxiety and body vigilance.

Intercellular adhesion molecule-1 (ICAM-1) is related to the occurrence and development of a variety of tumors. However, the role of ICAM-1 in the regulation of growth, metastasis, and clinical prognosis of the specific molecular subtypes of breast cancer, triple-negative breast cancer (TNBC), remains to be elucidated. This study explored the role of ICAM-1 in breast cancer and its triple-negative subtypes by systematic bioinformatics methods. The results showed that the expression of ICAM-1 in breast cancer tissues was significantly higher than that in normal tissues, especially in TNBC subtypes. In breast cancer, ICAM-1 mainly activates pathways related to apoptosis and epithelial–mesenchymal transition, while its overexpression in TNBC is associated with inflammatory response, apoptosis, and other processes. TNBC patients displaying higher ICAM-1 expression demonstrate enhanced responses to immunotherapy. High ICAM-1 expression is sensitive to drugs targeting tumor cell proliferation, apoptosis, and angiogenesis. In conclusion, breast cancer is characterized by significantly high expression of ICAM-1, with TNBC subtypes expressing ICAM-1 at much higher levels than other subtypes. The diagnosis, prognosis, development, distant metastases, and immunotherapy of TNBC are correlated with high expression of ICAM-1. This research provides available data for the further study of the diagnosis and treatment of TNBC.

Objective Our aim was to compare the costs and efficacy of ambroxol in combination with imiglucerase with the costs and efficacy of imiglucerase only in the treatment of Gaucher disease type 2 (GD2) in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy. Methods The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was 6 years. The main outcomes of the study were quality-adjusted life years gained with ambroxol + imiglucerase and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Markov chain model. The model results were obtained after Monte Carlo microsimulation of a sample with 1,000 virtual patients. Results Treatment with ambroxol in combination with imiglucerase was cost-effective when compared with imiglucerase only and was associated with positive values of net monetary benefit regardless of the onset of the disease. Such beneficial result for ambroxol and imiglucerase combination is primarily driven by the low cost of ambroxol and its considerable clinical effectiveness in slowing the progression of neural complications of GD2. Conclusion If ambroxol and imiglucerase are used in combination for the treatment of GD2, it is more cost-effective than using imiglucerase alone.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a low platelet (PLT) count and a high risk of bleeding, the clinical treatment for which still needs to be upgraded. Based on the critical role of human leukocyte antigen class II heterodimer β5 (HLA-DRB5) in immune system, we herein investigated its effect on ITP. ITP murine models were established by the injection of guinea pig anti-mouse platelet serum (GP-APS), and the PLT of mouse peripheral blood was counted during the modeling. Quantitative real-time reverse transcription polymerase chain reaction, western blot and immunofluorescence assay was performed to quantify expressions of HLA-DRB5, major histocompatibility complex II (MHC-II) and co-stimulatory molecules (CD80, CD86). Flow cytometry was conducted to analyze the percentage of CD8 + T cells. As a result, the PLT count was decreased in mouse peripheral blood. Expressions of HLA-DRB5, MHC-II and co-stimulatory molecules, as well as the percentage of CD8 + T cells were elevated in peripheral blood of ITP mice. HLA-DRB5 knockdown mitigated ITP by increasing peripheral PLT level, downregulating expressions of MHC-II and co-stimulatory molecules and inactivating CD8 + T cells. Collectively, the downregulation of HLA-DRB5 restores the peripheral PLT count in ITP mice by reducing MHC-II-mediated antigen presentation of macrophages to inhibit the activation of CD8 + T cells.

The objective of this study was to evaluate the efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome (CPPS). A total of 79 female patients diagnosed with CPPS from January 2021 to December 2022 were prospectively analyzed. Every patient received 3 weeks of treatment which included myofascial release therapy combined with electrical and magnetic stimulation. The visual analog score (VAS) of pelvic floor muscle (PFM) trigger points (TrPs) and the changes in pelvic floor surface electromyography before and after treatment were compared. Multiple linear regression was used to analyze the influencing factors of each outcome index. There were significant differences in VASs of muscle TrPs before and after treatment ( P < 0.05). For the surface electromyography of PFMs, the differences in pre-baseline rest, post-baseline rest, isometric contractions for muscle endurance evaluation, and coefficient of variation were statistically significant ( P < 0.05). Linear regression analysis showed that disease course ( X 1 ), dyspareunia ( X 5 ), and urinary incontinence ( X 6 ) were influencing factors for the decline of pre-baseline rest ( r 5 = 1.067, R 2 = 0.089), post-baseline rest ( r 1 = 0.055, r 5 = 0.99, R 2 = 0.119), VASs of ischial spine ( r 5 = 0.916, R 2 = 0.102), obturator internus ( r 5 = 0.796, r 6 = −0.703, R 2 = 0.245), and pubococcygeus ( r 5 = 0.885, R 2 = 0.149) after treatment in the CPPS group. This study confirmed that individualized myofascial release therapy combined with electrical and magnetic stimulation has significant efficacy for patients with CPPS. At the same time, it is more effective for CPPS patients with longer course of disease, dyspareunia, and without urinary incontinence.

Objective The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC). Methods This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05–0.075 mg/kg/day) or 36 received TAC (0.05–0.075 mg/kg/day) and GC (0.3–0.5 mg/kg/day of prednisone). Results At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar ( P > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups ( P > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant ( P < 0.05). Conclusion TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.

Background Rheumatoid arthritis (RA) is a chronic inflammatory and disabling disease that imposes significant economic and social costs. Tripterygium wilfordii Hook F (TwHF) has a long history of use in traditional Chinese medicine for treating joint disorders, and it has been shown to be cost-effective in treating RA, but its exact mechanism is unknown. Objective The goal of the network pharmacology analysis and molecular docking was to investigate the potential active compounds and associated anti-RA mechanisms of TwHF. Methods TCMSP and UniProt databases were searched for active compounds and related targets of TwHF. PharmGKB, DrugBank, OMIM, TTD, and the Human Gene Databases were used to identify RA-related targets. The intersected RA and TwHF targets were entered into the STRING database to create a protein–protein interaction network. R software was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking technology was used to analyze the optimal effective components from TwHF for docking with the selected target gene. Results Following screening and duplicate removal, a total of 51 active compounds and 96 potential targets were chosen. The PPI network revealed that the target proteins are CXCL8, CXCL6, STAT3, STAT1, JUN, PPARG, TP53, IL14, MMP9, VEGFA, RELA, CASP3, PTGS2, IFNG, AKT1, FOS, ICAM1, and MAPK14. The results of the GO enrichment analysis focused primarily on the response to lipopolysaccharide, the response to molecules of bacterial origin, and the response to drugs. The KEGG results indicated that the mechanisms were closely related to lipid and atherosclerosis, chemical carcinogenesis-receptor activation, Kaposi sarcoma-associated, herpesvirus infection, hepatitis B, fluid shear stress and atherosclerosis, IL-17 signaling pathways, Th17-cell differentiation, and so on, all of which are involved in angiogenesis, immune cell chemotaxis, and inflammatory responses. Molecular docking results suggested that triptolide was the appropriate PTGS1, PTGS2, and TNF inhibitors. Conclusion Our findings provide an essential role and basis for further immune inflammatory studies into the molecular mechanisms of TwHF and PTGS1, PTGS2, and TNF inhibitor development in RA.

Objective This research aims to investigate the role and underlying biological mechanism of FBXO45 in regulating ferroptosis of renal fibrocytes in a diabetic nephropathy (DN) model. Methods C57BL/6 mice were fed with a high-fat diet and injected with streptozotocin to induce diabetes. Human renal glomerular endothelial cells stimulated with d -glucose. Results Serum FBXO45 mRNA expression was found to be down-regulated in patients with DN. There was a negative correlation between the expression of serum FBXO45 mRNA and serum α-SMA, Collagen I, and E-cadherin mRNA in patients with DN. Additionally, the expression of serum FBXO45 mRNA showed a negative correlation with blood sugar levels. Based on a 3D model prediction, it was observed that FBXO45 interacts with polo-like kinase 1 (PLK1) at GLY-271, ILE-226, GLY-166, LEU-165, ARG-245, and ASN-220, while PLK1 interacts with FBXO45 at TYR-417, ARG-516, HIS-489, TYR-485, GLN-536, and ARG-557. This interaction was confirmed through immunoprecipitation assay, which showed the interlinking of FBXO45 protein with PLK1 protein. Conclusions These findings indicate that FBXO45 plays a role in mitigating ferroptosis in DN through the regulation of the PLK1/GPX4/SOX2 pathway. This highlights the potential of targeting FBXO45 as a therapeutic approach to ameliorate ferroptosis in DN.

Understanding the intricate relationship between cancer clinicopathological features and anesthetics dosage is crucial for optimizing patient outcomes and safety during surgery. This retrospective study investigates this relationship in patients with non-small cell lung cancer (NSCLC) undergoing video-assisted thoracic surgery (VATS). A comprehensive analysis of medical records was undertaken for NSCLC patients who underwent VATS with intravenous compound inhalation general anesthesia. Patients were categorized based on histological, chemotherapy, radiotherapy, and epidural anesthesia factors. Statistical analysis was performed to compare the differences between the groups. The results revealed compelling insights. Specifically, patients with lung adenocarcinoma (LUAD) undergoing VATS exhibited higher dosages of rocuronium bromide and midazolam during general anesthesia, coupled with a shorter post-anesthesia care unit (PACU) stay compared to those with squamous cell carcinoma (sqCL). Furthermore, chemotherapy patients undergoing VATS demonstrated diminished requirements for phenylephrine and remifentanil in contrast to their non-chemotherapy counterparts. Similarly, radiotherapy patients undergoing VATS demonstrated a decreased necessity for rocuronium bromide compared to non-radiotherapy patients. Notably, patients who received epidural anesthesia in combination with general anesthesia manifested reduced hydromorphone requirements and prolonged hospital stays compared to those subjected to general anesthesia alone. In conclusion, the findings from this study indicate several important observations in diverse patient groups undergoing VATS. The higher dosages of rocuronium bromide and midazolam in LUAD patients point to potential differences in drug requirements among varying lung cancer types. Additionally, the observed shorter PACU stay in LUAD patients suggests a potentially expedited recovery process. The reduced anesthetic requirements of phenylephrine and remifentanilin chemotherapy patients indicate distinct responses to anesthesia and pain management. Radiotherapy patients requiring lower doses of rocuronium bromide imply a potential impact of prior radiotherapy on muscle relaxation. Finally, the combination of epidural anesthesia with general anesthesia resulted in reduced hydromorphone requirements and longer hospital stays, suggesting the potential benefits of this combined approach in terms of pain management and postoperative recovery. These findings highlight the importance of tailoring anesthesia strategies for specific patient populations to optimize outcomes in VATS procedures.

Aim With unknown etiology and limited treatment options, unexplained recurrent pregnancy loss (URPL) remains a thorny problem. Ferroptosis, a newly identified type of cell death, has been shown to be crucial in the development in reproductive disorders. This study aims to explore the specific mechanism of ferroptosis in URPL and to uncover whether alpha-lipoic acid (ALA) can inhibit ferroptosis, and then exert a protective effect in URPL. Method The decidua tissues of URPL and control patients who actively terminated pregnancy were collected. The CBA/J × DBA/2 murine models of URPL were established, and were randomly treated with peroxisome proliferator activated receptor γ (PPARγ) agonists (Rosiglitazone) and ALA. The CBA/J × BALB/c murine models of normal pregnancy were intraperitoneally injected with PPARγ inhibitors (T0070907). Here, we used reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH)/GSSG, and FeRhoNox-1 analysis to detect the level of ferroptosis. We used quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis to evaluate the mRNA level of PPARγ. Besides, western blot and immunofluorescence were utilized to test the expression profile of PPARγ/nuclear factor erythroid 2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4). Results In this study, we found that iron deposition was increased in the decidual tissue of patients with URPL. Additionally, the changes in cell morphology, the level of ROS, MDA, GSH, and the expression of ferroptosis marker proteins NRF2/GPX4 confirmed activated ferroptosis in URPL. Besides, bioinformatics analysis combined with experiments confirmed that PPARγ was critical in triggering NRF2/GPX4 pathway in URPL. Furthermore, URPL mouse models were established, and the results showed that PPARγ/NRF2/GPX4-mediated ferroptosis was also significantly increased, which could be mitigated by ALA treatment. Conclusion Overall, these findings suggest that ferroptosis may play an important role in URPL, and ALA might be a promising therapeutic drug for improving pregnancy outcomes in URPL via targeting the PPARγ/NRF2/GPX4 pathway.

Community-acquired pneumonia (CAP) is a common respiratory disease in children. This prospective cohort study of 110 children with CAP and 100 healthy children investigated the relationship between the levels of vitamin A, D and E and inflammatory markers, such as tumour necrosis factor (TNF-a), interleukin-1 (IL-1), interleukin-10 (IL-10), neutrophils (NE) and C-reactive protein (CRP), in CAP. The haemoglobin, leukocyte concentration, NE, monocytes and CRP concentration in the CAP group showed significant differences ( P < 0.05). The levels of vitamin A, D and E in the CAP group were lower than those in the control group, while the levels of TNF-a and IL-1 were higher than in the control group; the differences were statistically significant ( P < 0.05). The IL-10 levels showed no significant differences ( P > 0.05). Pearson analysis revealed that the vitamin A, D and E levels were all correlated with the TNF-a, IL-10 and CRP levels ( P < 0.05). The vitamin A, D and E levels of the CAP children were lower than those of the healthy children. Thus, the content of fat-soluble vitamins is correlated with the secretion of TNF-a and IL-10. The research provides a new direction for the prevention, diagnosis and treatment of CAP.

The study aimed to investigate the effect of CD1d down-regulation on the proliferation, migration, and apoptosis of papillary thyroid carcinoma cells and explore the underlying mechanism. CD1d expression was silenced in TPC-1 cells by transfection of CD1d siRNA lentivirus. The proliferation, apoptosis rate, and migration ability of TPC-1 cells were detected by CCK-8 assay, flow cytometry, and scratch assay, respectively. Western blot and qPCR analyses were performed to detect the expression of related proteins. CD1d was highly expressed in TPC-1 cells. Down-regulation of CD1d significantly decreased ALMS1, CDKN3, CDK6, Ki-67, Bcl2 expression, increased Bax and Caspase 3 expression (all P < 0.05), and decreased the migration ability of TPC-1 cells. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to identify the relevant signaling pathways. KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly enriched in MAPK and NF-κB signaling pathways. Our findings suggest that CD1d down-regulation inhibited the proliferation and migration abilities of TPC-1 cells, increased cell apoptosis possibly via the MAPK/NF-κB signaling pathway.

Objective Sympathetic hyperinnervation following myocardial infarction (MI) is one of the primary causes of ventricular arrhythmias (VAs) after MI. Nerve growth factor (NGF) is a key molecule that induces sympathetic nerve remodeling. Previous studies have confirmed that microRNA (miR)-let-7a interacts with NGF. However, whether miR-let-7a is involved in sympathetic remodeling after MI remains unknown. We aimed to investigate whether miR-let-7a was associated with the occurrence of VA after MI. Methods and results A rat model of myocardial infarction was established using left coronary artery ligation. miR-let-7a expression levels were analyzed by reverse transcription-quantitative PCR. Western blotting was also used to examine NGF expression levels in vivo and in M1 macrophages in vitro . The relationship between miR-let-7a and NGF levels was investigated using a luciferase reporter assay. The results revealed that the expression of miR-let-7a decreased significantly after MI, while NGF expression was significantly upregulated. In addition, overexpression of miR-let-7a effectively inhibited NGF expression in rats, which was also verified in M1 macrophages. Tyrosine hydroxylase and growth-associated protein 43 immunofluorescence results revealed that the administration of a miR-let-7a overexpression lentivirus to rats inhibited sympathetic remodeling after MI. Programmed electrical stimulation, renal sympathetic nerve activity recording, and heart rate variability measurements showed that miR-let-7a overexpression decreased sympathetic activity. Conclusions These findings provide novel insights into the molecular mechanisms by which miR-let-7a and NGF contribute to the progression of sympathetic nerve remodeling after MI. Therefore, miR-let-7a may be a promising therapeutic target to reduce the incidence of arrhythmia following MI.

Objective This study aimed to evaluate the efficacy and safety of solid organ transplantation recipients inoculated with an inactivated COVID-19 vaccine. Methods We retrospectively analyzed the antibody levels and related adverse events of non-transplantation subjects and solid organ transplant recipients, both pre-transplantation (individuals awaiting organ transplantation) and post-transplantation (individuals who have undergone organ transplantation), who received inactivated COVID-19 vaccines from February 2021 to July 2022. Results The study included 38 pre-transplantation vaccination group, 129 post-transplantation vaccination group, and 246 non-transplantation group. The antibody titer was assessed monthly within the period of 1–12 months after the last injection. The antibody-positive rate among the three groups were 36.84, 20.30, 61.17% ( P < 0.05). The antibody-positive rates among three groups with one, two doses vaccine were not significantly different ( P > 0.05), but were significantly different after three doses ( P < 0.05). The antibody titers among three groups were significantly different after two doses ( P < 0.05). Adverse reactions occurred in six transplant recipients, which were relieved after treatment, and not in the non-transplantation subjects. Conclusion Inactivated COVID-19 vaccine is safe and effective for solid organ transplantation recipients, at least two doses of which should be completed before organ transplant surgery.

This research delves into the influence of H2Valdien derivatives on the proliferation, migration, and apoptosis induction in hepatoma carcinoma cells (HepG2, Huh-7, and SMMC-7721), with a specific emphasis on inhibiting epithelial–mesenchymal transition (EMT) through modulation of the Hedgehog (Hh) signaling pathway. Utilizing the cell counting kit-8 method, flow cytometry, TUNEL assay, wound healing, and transwell assays, we observed a dose-dependent growth arrest and apoptosis induction in HepG2, Huh-7, and SMMC-7721 cells. Notably, H2Valdien derivatives exhibited a capacity to reduce migration and invasion, impacting the expression of EMT-associated proteins such as N -cadherin, vimentin, and E-cadherin. Mechanistically, these derivatives demonstrated the inhibition of the Hh signaling pathway by inactivating Sonic Hh (Shh) and smoothened proteins. This study underscores the robust antiproliferative and apoptosis-inducing effects of H2Valdien derivatives on hepatoma carcinoma cells and elucidates their regulatory role in EMT through modulation of the Hh signaling pathway, providing valuable insights for potential therapeutic interventions.

Objective To investigate the clinical efficacy of dexamethasone (Dex) combined with isoniazid in tuberculous meningitis (TBM) and its effect on peripheral blood T cell subsets. Methods A total of 235 patients with TBM were divided into the control group (117 cases) and the observation group (118 cases). Both groups were given conventional treatment, the control group was further given isoniazid, and the observation group was further given Dex combined with isoniazid. The therapeutic effect and improvement of clinical symptoms were evaluated, peripheral blood T lymphocyte subsets and neurological function were observed, and patients’ prognosis was evaluated. Results The total effective rate of the observation group was higher. The recovery time of cerebrospinal fluid (CSF) pressure, CSF protein content, CSF cell count, and hospital stays in the observation group were shorter. The duration of cervicogenic headache, fever, vomiting, and coma in the observation group was shorter. CD3 + and CD4 + /CD8 + proportions in the observation group were higher, and CD8 + proportion was lower. The NIHSS score and MRS score of the observation group were lower, as well as the incidence of adverse reactions. Conclusion Dex combined with isoniazid alleviates clinical symptoms and neurological abnormalities and regulates peripheral blood T cell subsets in TBM.

The bleeding time and amount in the short-segment group were shorter than in the long-segment group, and the bleeding volume was less than in the long-segment group. The Japanese Orthopaedic Association low back pain score, Oswestry Dysfunction Index, and lumbar spine stiffness disability index score of the two groups were significantly improved preoperatively, postoperatively, and at 6 months, 1 year, and 2 years post-operation. The differences were statistically significant at different time points within the groups. Neurological function improved to varying degrees postoperatively. The Cobb angle was significantly higher in both groups ( P < 0.05). Adjacent vertebral disease occurred in 10 of 64 patients with short-segment fixation, with a prevalence of 15.6%. Preoperative pelvic tilt angle, preoperative pelvic projection angle (PPA), preoperative degree of matching of PPA to LL (PI-LL), and preoperative coronal Cobb angle were higher in patients with adjacent vertebral disease. There were varying degrees of improvement in low back pain and spinal function after short-segment decompression and fusion internal fixation. However, the patients are generally elderly and at risk of persistent low back pain and accelerated degeneration of adjacent segments.

The malfunction of endothelial progenitor cells (EPCs) due to ox-LDL is a risk contributor for arteriosclerotic disease. Meanwhile, lycopene possesses anti-inflammatory and antioxidative qualities. This investigation aimed to determine if lycopene can protect EPCs from ox-LDL-induced damage and to elucidate the underlying mechanism. The effects of lycopene on the survival, migration, and tube-forming capacity of EPCs were determined via in vitro assays. Expression of proteins related to pyroptosis and cellular proteins related to AMPK/mTOR/NLRP3 signaling was determined by western blot/flow cytometry. Our results demonstrated that lycopene treatment significantly enhanced proliferation, tube formation, and migration of EPCs stimulated by ox-LDL. Additionally, lycopene was found to suppress pyroptosis in ox-LDL-induced EPCs through the activation of AMPK, which led to the inhibition of mTOR phosphorylation and subsequent downregulation of the downstream NLRP3 inflammasome. In summary, our study suggests that lycopene mitigates ox-LDL-induced dysfunction in EPCs and inhibits pyroptosis via AMPK/mTOR/NLRP3 signaling. Our study suggests that lycopene may act as promising therapies for preventing atherosclerosis.

Leukemia, the most common malignant tumor in childhood, can be categorized into acute leukemia and chronic leukemia. However, the role of FUNDC1 in childhood leukemia (CL) remains unknown. This study aims to investigate the effects of FUNDC1 on patients with CL and its underlying mechanism both in vivo and in vitro . The mRNA expression levels of FUNDC1 were found to be up-regulated in serum samples from CL patients as well as in leukemia cell lines. Furthermore, it was observed that the mRNA expression of FUNDC1 was lower in stage I–II CL patients compared to stage III–IV patients. The up-regulation of FUNDC1 was found to promote leukemia metastasis. Additionally, it was discovered that FUNDC1 up-regulation reduces ferroptosis by inhibiting mitochondrial damage. In a leukemia model, FUNDC1 up-regulation induces the expression of FBXL2. Moreover, FUNDC1 up-regulation reduces FBXL2 ubiquitination, thus maintaining FBXL2 protein expression in leukemia. By inducing FBXL2, FUNDC1 reduces ferroptosis in leukemia through the inhibition of mitochondrial damage. The stability of FUNDC1 is controlled by METTL3 methylation. Overall, this study sheds light on the role of FUNDC1 in CL and provides insights into its underlying mechanisms.

Objective Our aim was to examine the significance of single-fiber electromyography (SFEMG) in patients diagnosed with amyotrophic lateral sclerosis (ALS) and determine the best correlating parameter with SFEMG parameters and clinical scales across different muscles including facial muscles. Methods SFEMG examinations were conducted on the extensor digitorum (ED), frontalis, and orbicularis oculi muscles. Mean jitter, percentage of increased jitter, fiber density (FD), and impulse blocking percentage were compared to reference values and functional scales. Results Significant differences ( p < 0.001) were observed between the patients’ SFEMG results and reference values in all muscles. Significant correlations were found between SFEMG parameters and clinical scales, particularly when considering both FD and jitter. A notable value of the ALS Functional Rating Scale Revised (ALSFRS-R) was detected in all muscles: 31 points in the ED muscle, 30 in the orbicularis oculi muscle, and 31 in the frontalis muscle. Below this ALSFRS-R threshold, the percentage of increased jitter was higher, while FD remained relatively low. Conclusion SFEMG examination emerges as a valuable tool for better understanding ALS and holds potential for assessing prognosis. Combined jitter and FD analysis showed the strongest correlation with clinical scales. In addition to the ED muscle, the orbicularis oculi muscle may be important in the assessment.

The aim of the present study was to explore the risk factors of postoperative airway complications in children with oral floor mass. The first choice of auxiliary examination method for children with oral floor mass is also proposed. This retrospective study included 50 children with floor-of-mouth (FOM) masses. Medical records were reviewed, and information on age of onset, functional impacts present, age at consultation, imaging findings, history of preoperative aspiration, pathology findings, properties of biopsied fluid, treatment modality, postoperative outcomes, and operation were recorded. A total of 20 patients exhibited functional impacts such as difficulty in breathing and feeding. Ultrasound examination was performed in 28 cases; and magnetic resonance imaging, in 38 cases. The diagnosis was lymphatic malformation in 12 cases, developmental cyst in 29 cases, and solid mass in 7 cases. There were 28 cases of surgical resection, 9 cases underwent multiple puncture volume reduction followed by surgery, 11 cases treated using sclerotherapy injection, and 1 case treated using sclerotherapy injection and surgical resection. Young age, functional impact, and high grade of lymphatic duct malformation increased the risk of surgical treatment. B-scan ultrasound is the first choice for the diagnosis of FOM masses in children.

Acute cerebral infarction (ACI) is a lethal disease whose early diagnosis is critical for treatment. microRNA (miR)-19a targets CC chemokine ligand 20 (CCL20) in myocardial infarction. We investigated the expression patterns of serum miR-19a and CCL20 of ACI patients and assessed their clinical values. Serum samples of 50 healthy subjects and110 ACI patients were collected. Serum levels of miR-19a, CCL20 mRNA, and biochemical indexes were assessed. miR-19a downstream target gene and the binding relationship between miR-19a and CCL20 were predicted and verified. miR-19a and CCL20 mRNA were subjected to correlation and diagnostic efficiency analysis. miR-19a was poorly expressed in the serum of ACI patients, especially in patients with unstable plaque and large infarction. tumor necrosis factor-α, low-density lipoprotein, and platelet/lymphocyte ratio negatively correlated with serum miR-19a level and positively correlated with CCL20. Dual-luciferase assay revealed that miR-19a could negatively regulate CCL20 expression. CCL20 was highly expressed in the serum of ACI patients. The area under receiver-operating characteristic curve of miR-19a combined with CCL20 was 0.9741 (98.00% specificity, 90.91% sensitivity), higher than their single diagnosis. Collectively, miR-19a had high diagnostic value for ACI and could target to restrain CCL20. The combination of miR-19a and CCL20 improved diagnostic value for ACI.

Objective Mental health significantly affects the physical and emotional development of adolescents. The aim of the current study was to examine how physical activity (PA) and mental health among Korean adolescents changed before and after the start of the COVID-19 pandemic. Methods We used comparative cross-sectional methods, gathering information from the Korea Disease Control and Prevention Agency databases and conducting Chi-square testing and correlation analysis for evaluation. Results The findings indicate that before and during the pandemic, participation in both moderate- and high-intensity PA, as well as strength training, mitigated stress, depression, and suicidal ideation. Furthermore, the findings confirm the beneficial effects of various physical activities on mental well-being. Conclusions These insights emphasize the vital role of regular PA in improving mental health among adolescents, particularly during a health crisis such as the pandemic.

Objective The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients. Methods Patients with HIV infection combined with anemia admitted to the Kunming Third People’s Hospital were retrospectively collected and divided into mild anemia, moderate anemia, and severe anemia groups by peripheral hemoglobin (HB) content and calculated the ratio of ventricular septum density (VSD) to left ventricular density (LVD) and VSD to right ventricular density (RVD); then, the above patients were divided into the critical value group and the non-critical value group according to HB and compared the differences of LVD, RVD, VSD/LVD, and VSD/RVD in the two groups of patients. Results A total of 126 patients were included, with a mean age of 47.9 ± 11.1 years; 43 cases were in the mild anemia group, 59 cases were in the moderate anemia group, and 24 cases were in the severe anemia group; the differences in LVD, RVD, VSD/LVD, and VSD/RVD were significant in the three groups; VSD/LVD was an independent predictor for the diagnosis of anemia critical value in the non-critical value group vs critical value group by multifactorial binary logistic regression analysis, and the ROC was plotted using VSD/LVD with an area under the curve of 0.731. Conclusions The measurement of cardiac cavity density and ventricular septal density under CT plain film scan has a high accuracy in evaluating the severity of anemia in patients with HIV infection and can quickly determine the severity of HIV infection in the early stage and treat it as soon as possible.

Purpose Ponticulus posticus (PP) is a bony protrusion located between the posterior portion of the superior articular process and the posterolateral portion of a posterior arch of the atlas vertebrae in the cervical spine. The aim of this study is to verify the presence of different types of PP in a Southern Italian pre-orthodontic cohort to understand its correlation with skeletal class and maturity. Methods A case–control retrospective study was conducted, utilizing 212 latero-lateral telecranium radiographs to analyze skeletal maturity according to the cervical vertebral maturation method, the Angle’s classification of malocclusion (I, II, or III), and the presence or absence of the PP, whether complete (c-PP) or partial (p-PP). A total of 212 lateral cephalograms were analyzed. Results Of the 72 male patients, 67 (93%) exhibited PP, and 116 (88%) were PP. The chi-square value was 0.001, while Cramer’s V was 0.270, indicating a significant correlation between age groups and PP presence, and a very strong association overall. Out of the 41 complete PP cases, class I was notably more prevalent than classes II and III. Conclusion Orthodontists should carefully consider PP when assessing and treating individuals with or without skeletal discrepancies and dental anomalies.

Background Malignant lymphoma (ML) is a group of malignant tumors originating from the lymphatic hematopoietic system. Previous studies have found a correlation between circulating immune cells and ML. Nonetheless, the precise influence of circulating immune cells on ML remains uncertain. Methods Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and ML risk. A total of four types of immune signatures, median fluorescence intensities, relative cell, absolute cell, and morphological parameters were included. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between circulating immune cells and the risk of ML. Sensitivity analysis was conducted using Cochran’s Q test, the Mendelian randomization Egger regression intercept test, and leave-one-out analysis. Results ML had a statistically significant effect on immunophenotypes. Twenty-three immunophenotypes were identified to be significantly associated with Hodgkin lymphoma risk through the IVW approach, and the odds ratio values of CD64 on CD14 − CD16 + monocyte [2.31, 95% confidence interval (CI) = 1.41–3.79, P 1 = 0.001], IgD + CD24 + B-cell %lymphocyte (2.06, 95% CI = 1.13–3.79, P 1 = 0.018), B-cell %lymphocyte (1.94, 95% CI = 1.08–3.50, P 1 = 0.027), CD24 + CD27 + B-cell %lymphocyte (1.68, 95% CI = 1.03–2.74, P 1 = 0.039), and CD14 + CD16 − monocyte %monocyte (1.60, 95% CI = 1.15–2.24, P 1 = 0.006) ranked in the top five. Eleven immunophenotypes were identified to be significantly associated with non-Hodgkin lymphoma risk, CD86 on granulocyte (2.35, 95% CI = 1.18–4.69, P 1 = 0.015), CD28 − CD8 + T-cell absolute count (1.76, 95% CI = 1.03–2.99, P 1 = 0.036), CCR2 on myeloid dendritic cell (CD24 + CD27 + B cell, 95% CI = 1.02–1.66, P 1 = 0.034), CD3 on effector memory CD8 + T cell (1.29, 95% CI = 1.02–1.64, P 1 = 0.012), and natural killer T %lymphocyte (1.28, 95% CI = 1.01–1.62, P 1 = 0.046) were ranked in the top five. Conclusion This study presents compelling evidence indicating the correlation between circulating immune cells and lymphoma, thus providing guidance for future clinical research.

To investigate the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals in the treatment of renal fibrosis (RF). We searched articles from databases (PubMed, Embase, The Cochrane Library, CNKI, and Wanfang data) and references of included studies. The quality of literature was evaluated and data were extracted in regard to the inclusion and exclusion criteria. RevMan5.3 software was applied for all statistical analyses. Eleven eligible RCTs with a total of 898 patients were included in this meta-analysis. Compared with conventional western medicine alone, conventional western medicine with Chinese medicine for dredging collaterals in the treatment of RF has lower BUN levels and SCr levels ( P < 0.05). As for fibrosis indexes, conventional western medicine with Chinese medicine for dredging collaterals has lower HA, laminin (LN), IV-Col, and PC-III levels ( P < 0.05). Conventional western medicine with Chinese medicine for dredging collaterals with lower BUN, Scr, HA, LN, PC-III, and IV-Col levels, has an advantage in the treatment of RF. These lower serum levels may not be associated with the presence of RF. Ideally, kidney biopsies should be performed to confirm that these markers reduce RF. This is a major limitation of this study.

Backgrounds The integrator complex (INT) is a multiprotein assembly in gene transcription. Although several subunits of INT complex have been implicated in multiple cancers, the complex’s role in gastric cancer (GC) is poorly understood. Methods The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein–protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC. Results The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5′–3′ RNA polymerase activity. Moreover, these INT subunit expressions were associated with tumor-infiltrating lymphocytes and MSI in GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inhibits cell proliferation ability. INTS11 overexpression showed opposite effects. Conclusions Our data demonstrate that the INT complex might act as an oncogene and can be used as a prognosis biomarker for GC.

Background No intervention definitively extends transplant-free survival in primary sclerosing cholangitis (PSC). Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), may enhance PSC prognosis, but their efficacy is debated. Methods We analyzed HMGCR single-nucleotide polymorphisms from published genome-wide association studies using Mendelian randomization to assess the causal relationship between HMGCR and PSC risk. Effects of HMGCR were compared with proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, common lipid-lowering drugs, using coronary heart disease risk as a positive control. The inverse-variance weighted (IVW) method was the primary analysis, complemented by the weighted median method. Heterogeneity analysis, examination of horizontal pleiotropy, and leave-one-out sensitivity analysis were conducted for result robustness. Results Genetically predicted HMGCR exhibited a pronounced detrimental effect on PSC in both the IVW method (odds ratio [OR] [95%] = 2.43 [1.23–4.78], P = 0.010) and the weighted median method (OR [95%] = 2.36 [1.02–5.45], P = 0.044). However, PCSK9 did not reach statistical significance. Moreover, all analyses passed through heterogeneity analysis, horizontal pleiotropy analysis, and leave-one-out sensitivity analysis. Conclusion This study has confirmed a causal relationship between HMGCR and PSC risk, suggesting statins targeting HMGCR could enhance PSC patient outcomes.

Objective The pharmacokinetics of meropenem are significantly altered in critically ill patients. A population pharmacokinetic study was designed to estimate typical values of meropenem clearance in critically ill patients and evaluate potential factors of influence. Methods After meropenem reached a steady state in each patient, two blood samples were taken within the dose interval. The one-compartment pharmacokinetic model based on the data from 101 intensive care unit patients was built using NONMEM software. Results Typical values of meropenem clearance and volume of distribution were 3.80 L/h and 3.52 L, respectively. In the final model, meropenem clearance was influenced by serum concentrations of creatinine (CRE), leukocyte count (WBC), hypertension (HTA), and concomitant use of vancomycin (VAN) or colistimethate (COL): CL (L/h) = 5.29 × CRE ^ 0.000001 × WBCs ^ (−0.165) + 0.000001 × HTA + 0.825 × VAN + 1.28 × COL. Conclusion In order to achieve effective plasma concentrations of meropenem in critically ill patients, the meropenem dosing regimen should be adjusted according to individual values of drug clearance.

Introduction Acute appendicitis (AA) is the predominant condition responsible for acute abdominal pain across all age demographics. The purpose of this research is to determine if the hemoglobin, albumin, lymphocyte, and platelet (HALP) and modified HALP (m-HALP) scores differ between complicated and uncomplicated appendicitis in patients diagnosed with AA who have applied to the emergency department (ED). Additionally, this study aims to investigate whether HALP and m-HALP scores are superior to other biomarkers. Materials and methods The retrospective analysis included adult patients, aged eighteen or older, who were diagnosed with AA, and sought treatment at the ED of a tertiary hospital. Patients were divided into two groups: complicated appendicitis (CA) and uncomplicated appendicitis (UCA). The cut-off in diagnostic value measurements was determined using the receiver operating characteristic analysis. Results A total of 436 patients (CA: 126, UCA: 310) were included. Neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-albumin ratio, systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune inflammation value (PIV) were found to have acceptable diagnostic power in CA detection (area under the curve [AUC]: 0.735–0.783). In detecting UCA, HALP and m-HALP were of fair diagnostic power (AUC: 0.64, 0.68, respectively). Conclusions In this study, we found that although PIV, SIRI, SII, and NLR had acceptable diagnostic values in distinguishing CA and UCA, HALP and m-HALP had fair diagnostic values.

Background The anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) are important structures to maintain knee stability. The present study aimed to further enrich understandings of the morphology of the cruciate ligaments and explore the relationship between the diameter of ACL and PCL. Method This study collected valid MRI samples of 50 male and 50 female normal right knee joints and measured the diameter of each point of the ACL and PCL through the 3D Slicer. Results The diameter of the ACL in the sagittal MRI of the normal right knee joint was significantly different from the diameter of each point of the PCL. The average diameter of each point of the ACL was larger than the diameter of the corresponding point of the PCL. Males and females had statistical differences in their PCL origin point, PCL midpoint, ACL origin point, ACL midpoint, and ACL insertion point diameters under sagittal MRI examination. The average diameter of males was greater than the average diameter of females at the above corresponding sites. In sagittal MRI scans of the normal right knee joint, we observed that only the origin point of the PCL exhibited a moderate correlation with the midpoint and insertion point of the ACL in terms of their respective diameters. Conclusion The correlation between diameters of normal ACL and PCL in knee joint MRI was moderate and may help clinicians determine appropriate graft for cruciate ligament reconstruction surgery quickly for severe cruciate ligament injuries.

Objective This study aims to address the substantive issue of lacking reliable prognostic biomarkers in hepatocellular carcinoma (HCC) by investigating the relationship between TP53-inducible glycolysis and apoptosis regulator (TIGAR) and HCC prognosis using The Cancer Genome Atlas database. Methods (1) Integrated statistical analyses, including logistic regression, Wilcoxon signed-rank test, and Kruskal–Wallis test, were conducted to explore the association between TIGAR expression and clinical–pathological features of HCC. (2) The Kaplan–Meier method combined with univariate and multivariate Cox regression models underscored TIGAR as a prognostic factor in HCC. (3) Gene set enrichment analysis (GSEA) revealed key pathways associated with TIGAR, while single-sample gene set enrichment analysis (ssGSEA) determined its relevance to cancer immune infiltration. Results (1) Elevated TIGAR expression was significantly correlated with decreased survival outcomes in HCC patients. (2) GSEA highlighted the significant link between TIGAR and humoral immunity. (3) ssGSEA revealed a positive correlation between TIGAR expression and infiltration of Th1 and Th2 cells and a negative correlation with Th17 cell infiltration. Conclusion TIGAR, as a potential prognostic biomarker for HCC, holds significant value in immune infiltration. Understanding the role of TIGAR could contribute to improved prognostic predictions and personalized treatment strategies for HCC patients.

Objective In this prospective observational study, we aimed to investigate the serum levels of sirtuin (SIRT)3 in epilepsy patients and its association with the severity of the disease. Methods This prospective observational study included 203 patients with symptomatic epilepsy and 100 healthy controls who visited our hospital from November 2019 to November 2022. The severity of the disease in epilepsy patients was assessed using the National Hospital Seizure Severity Scale (NHS3). We used enzyme-linked immunosorbent assay to measure the serum levels of SIRT3, interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha, and C-reactive protein in all patients. In addition, the cognitive function of all study participants was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment (MOCA). All data were analyzed using SPSS 25.0 software. Results The MOCA scores of the epilepsy patients were significantly lower compared to the healthy volunteers ( P < 0.05). The serum SIRT3 levels were decreased significantly in patients with refractory epilepsy (183.16 ± 17.22 pg/mL) compared to non-refractory epilepsy patients (199.00 ± 18.68 pg/mL). In addition, serum SIRT3 levels were negatively correlated with the inflammatory factors IL-6 (Pearson’s correlation −0.221, P = 0.002) and NHS score (Pearson’s correlation −0.272, P < 0.001) of epilepsy patients, while positively correlated with MOCA scores (Pearson’s correlation 0.166, P = 0.018). Furthermore, the receiver operating characteristic curve demonstrated that serum SIRT3 could be used to diagnose epilepsy, as well as refractory epilepsy. Finally, logistic regression analysis showed that SIRT3 (OR = 1.028, 95%CI: 1.003–1.054, P = 0.028), IL-6 (OR = 0.666, 95%CI: 0.554–0.800, P < 0.001), IL-1β (OR = 0.750, 95%CI: 0.630–0.894, P = 0.001), and NHS3 (OR = 0.555, 95%CI: 0.435–0.706, P < 0.001) were risk factors for refractory epilepsy. Conclusion In conclusion, our findings demonstrated that serum SIRT3 levels were significantly decreased in epilepsy patients and further decreased in patients with refractory epilepsy. This study might provide new therapeutic targets and comprehensive treatment strategies for epilepsy patients.

Src-homology region 2 domain-containing phosphatase 1 (SHP-1) is considered an anti-inflammatory factor, but its role in chronic obstructive pulmonary disease (COPD) remains unknown. Herein, overexpression of SHP-1 was utilized to explore the functions of SHP-1 in COPD models established by stimulating 16HBE cells with cigarette smoke extracts (CSE) in vitro . SHP-1 was downregulated in both COPD patients and CES-treated 16HBE cells. SHP-1 overexpression reinforced cell viability and significantly prevented CSE-induced cell apoptosis in 16HBE cells. Furthermore, SHP-1 overexpression greatly reversed the CSE-induced migration, epithelial–mesenchymal transition (EMT), and pro-inflammatory factor production in 16HBE cells. In addition, CSE activated the P65 and PI3K/AKT pathways in 16HBE cells, which was also reversed by SHP-1 overexpression. Our findings indicated that SHP-1 alleviated CSE-induced EMT and inflammation in 16HBE cells, suggesting that SHP-1 regulated the development of COPD, and these functions may be linked to the inhibition of the PI3K/AKT pathway.

Background Neural cell damage is an important cause of exacerbation of depression symptoms caused by hypoxia, but the mechanism behind it is still unclear. The purpose of this study is to elucidate the role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/mitofusin-2 (MFN2) signaling axis in the development of depression in mice under hypoxia. Methods Male Institute of Cancer Research mice (age, 6 weeks) were assigned to the normal group, chronic unpredictable mild stress group (CUMS group), or CUMS + hyper-hypoxia group (CUMS + H group). Mice in the CUMS and CUMS + H groups were exposed to CUMS for 28 days. Additionally, mice in the CUMS + H group were exposed to acute hyper-hypoxia from Day 21 for 7 days. After a total of 28 days, behavioral experiments were conducted. All mice were anesthetized and sacrificed. Levels of brain tissue interleukin (IL)-6, reactive oxygen species (ROS), adenosine triphosphate (ATP), and serotonin (5-HT) were analyzed. Results As compared to the CUMS group, mice in the CUMS + H group had increased IL-6 and ROS levels, but lower open-field activity, preference for sucrose, hippocampal neuronal membrane potential, ATP, and 5-HT levels, as well as MFN2 and PGC1α levels. Conclusions Acute hyper-hypoxia plays an important role in the development of depression via the IL-6/PGC1α/MFN2 signaling pathway.

Gap junction protein beta 3 ( GJB3 ) has been reported as a tumor suppressor in most tumors. However, its role in lung adenocarcinoma (LUAD) remains unknown. The purpose of this study is to explore the role of GJB3 in the prognosis and tumor microenvironment of LUAD patients. The data used in this study were acquired from The Cancer Genome Atlas, Gene Expression Omnibus, and imvigor210 cohorts. We found that GJB3 expression was increased in LUAD patients and correlated with LUAD stages. LUAD patients with high GJB3 expression exhibited a worse prognosis. A total of 164 pathways were significantly activated in the GJB3 high group. GJB3 expression was positively associated with nine transcription factors and might be negatively regulated by hsa-miR-6511b-5p. Finally, we found that immune cell infiltration and immune checkpoint expression were different between the GJB3 high and GJB3 low groups. In summary. GJB3 demonstrated high expression levels in LUAD patients, and those with elevated GJB3 expression displayed unfavorable prognoses. Additionally, there was a correlation between GJB3 and immune cell infiltration, as well as immune checkpoint expression in LUAD patients

There is limited evidence regarding the effect of circuit-type low-intensity resistance exercise on physical fitness and blood parameters in breast cancer survivors (BCSs). Therefore, this study aimed to investigate the effect of low-intensity circuit resistance exercise on changes in physical fitness and blood parameters in BCSs. A total of 16 BCSs participated in a low-intensity circuit resistance exercise group (LCREG). The exercise program in the LCREG consisted of 50–60% of one repetition maximum, two to three times weekly, for 24 weeks. The control group (CG) did not receive any interventions. All participants were measured for physical fitness and blood parameters before and after the exercise intervention. The results showed that LCREG significantly improved body mass index (BMI) ( p = 0.012), grip strength ( p = 0.017), back strength ( p = 0.042), plank ( p = 0.036), balance ( p = 0.030), low-density lipoproteins (LDL) ( p = 0.050), total cholesterol ( p = 0.017), and natural killer cell activity (NKCA) ( p = 0.035) after exercise compared to before exercise. The LCREG also significantly improved BMI ( p = 0.001), grip strength ( p = 0.014), plank ( p = 0.018), balance ( p = 0.012), LDL ( p = 0.024), total cholesterol ( p = 0.012), and NKCA ( p = 0.036) compared to the CG. These findings suggest that low-intensity circuit resistance exercise can increase physical fitness levels and improve the blood index in BCSs.

Background This study leverages the GSE4386 dataset, obtained from atrial tissue samples post-coronary artery bypass graft (CABG) surgery, to investigate the impact of anesthetic agents (sevoflurane and propofol) on gene expression and immune cell infiltration. Methods Hierarchical clustering and box plots were employed for dataset preprocessing, highlighting a significant outlier (sample GSM99282), subsequently removed to ensure data integrity. Differentially expressed genes (DEGs) were identified using volcano plots based on specific log-fold-change and P -value thresholds. Additional analyses included the Friends approach, Spearman’s correlation, and gene set enrichment analysis (GSEA), exploring functional annotations and pathways. Results Heatmaps and bubble plots depicted DEGs, revealing distinct expression patterns between the sevoflurane and propofol groups. Friends analysis identified top genes based on log fold changes, further correlated using Spearman’s method. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses illustrated functional annotations of DEGs, while GSEA highlighted enriched biological categories. Immune cell infiltration analysis showcased varied cellular presence post-CABG. ESTIMATE algorithm scores demonstrated differences in immune, stroma, and estimate scores. Microenvironment Cell Populations-counter (MCPcounter) revealed an increased abundance of cytotoxic lymphocytes in the sevoflurane group, confirmed by a single sample GSEA. CIBERSORT algorithm identified distinct immune cell compositions, highlighting differences in macrophage M0 prevalence between sevoflurane and propofol groups. Conclusions This comprehensive analysis provides insights into anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-CABG surgery. The identified DEGs and immune cell compositions offer potential biomarkers and therapeutic targets for refining anesthetic strategies in cardiac surgeries.

Background Empagliflozin has been shown in clinical studies to lower the risk of adverse cardiovascular events. Using proteomics, the current study aims to determine whether empagliflozin reduces aortic alterations in obese mice and to investigate its molecular mechanism of action. Methods We constructed obese mice and then treated them with empagliflozin. Changes in the weight of the mice were recorded. Blood glucose and lipid levels were measured in each group of mice, and changes in pulse wave velocity and aortic structure were recorded. In addition, changes in aortic protein expression were detected by proteomics and analyzed bioinformatically. Results Proteomics results showed that 507 differentially expressed proteins (DEPs) were identified in the comparison of normal and obese mice, while 90 DEPs were identified in the comparison of obese and empagliflozin-treated mice. Examination of these three groups revealed that DEPs were largely associated with the digestion of unsaturated fats. Among them, empagliflozin significantly reduced the expression of fatty acid synthase (FASN), acyl-CoA desaturase 3 (SCD3), ACSL1. and ACSL5 in the aorta of obesity-induced mice, and there was a close relationship between the four. Conclusion Empagliflozin reduced the protein expression of FASN, SCD3, ACSL1, and ACSL5 in the aorta of obese mice and improved aortic fatty acid metabolism and reduced vascular stiffness for vasoprotective effects.

To analyze the related factors of radiation-induced encephalopathy in nasopharyngeal carcinoma (NPC) to identify the risk factors and their clinical significance. This retrospective cohort study included 707 NPC patients. They had undergone conventional and enhanced computed tomography or magnetic resonance imaging scans. They were divided into the radiation-induced encephalopathy group and the no encephalopathy group according to the imaging examination. Detailed clinical information was collected. The incidence of radiation-induced encephalopathy in NPC was 22.2%, in which 124 were radiation-induced encephalopathy and 33 were reirradiation patients. We found that age, pathological type, radiation method, hypertension, radiation course, relapse, carotid/cerebral arteriosclerosis, clinical stage, and radiotherapy dose were statistically significant between the two groups ( p < 0.05). Multiple logistic regression showed that clinical stage, age, radiotherapy method, hypertension, carotid/cerebral arteriosclerosis, and radiation courses after a reoccurrence of NPC were risk factors for radiation-induced encephalopathy. The more advanced the clinical stage was and the older the patient, the greater the risk. Radiotherapy method, radiation course, hypertension, carotid/cerebral arteriosclerosis, age, and clinical stage were the risk factors associated with radiation-induced encephalopathy in NPC. Graphical abstract

Objective To evaluate the reproductive outcomes of patients bearing BRCA-1 and BRCA-2 mutations. Methods In this retrospective observational cohort study, we assessed data from BRCA-1 and BRCA-2 carriers, analyzing demographics, oncological history, and reproductive outcomes. Statistical analysis compared BRCA-1 and BRCA-2 carriers. A thorough review of the literature was carried out. Results Fifty-eight patients were included. BRCA-1 and BRCA-2 mutations were equally distributed. Eighty-nine pregnancies occurred in our series, hesitated in 73 live births and 19 miscarriages. Mean age at first and last pregnancy was 27.8 ± 4.8 and 31.6 ± 4.8 years old. Thirty-nine patients have had at least one live birth (67.2%). Mean number of live births was 1.9 ± 0.6. Live birth rate (LBR) was 81.1% and miscarriage rate was 32.8%. Spontaneous fertility was unaltered, as evidenced by high LBR. Subgroup analysis revealed no significant differences between BRCA-1 and BRCA-2 carriers. Conclusions Our results shows that spontaneous reproductive outcomes in BRCA-mutated patients are reassuring. Despite evidence indicating a decrease in ovarian reserve among BRCA patients, this factor seems to not impact spontaneous fertility negatively. Further research is needed, and individuals with BRCA mutations should consider early family planning and fertility preservation in case of partner absence. Graphical abstract Despite evidence indicating a decrease in ovarian reserve among BRCA patients, this factor seems to not impact their spontaneous fertility negatively.

Objectives Studies have shown that there are differences in clinical evaluation parameters and difficult intubation rates among different ethnic populations. In our study, we aimed to evaluate the efficacy of upper airway clinical and ultrasonographic measurement methods in Turkish population. Methods Our study is a single-center, prospective, observational study conducted with 402 patients. All patients underwent clinical airway measurements which are routinely used in pre-anesthetic evaluation. In addition, ultrasonographic anterior neck soft tissue thickness measurements of each patient were made and recorded. Results Among the clinical measurements, we found the neck circumference/thyromental distance (TMD) ratio to be significant with a cut-off value of 5.5 and a sensitivity of 92.9% and a specificity of 88.3%, while among the ultrasonographic anterior neck measurements, we found the skin–epiglottic distance to be the most sensitive measurement. We found that there was a positive relationship between the neck circumference/TMD ratio and skin–epiglottis. Conclusions In our study, we found that routine measurement methods used in airway examination alone are not sufficient, and measurements that take into account the body proportions of the patients, such as the neck circumference/TMD ratio and the ultrasonographic evaluations are more useful in predicting difficult intubation.

Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in tumor tissues of several malignancies, including pancreatic cancer. Because of its role in tumor progression, IGFBP2 has been investigated as a tumor biomarker. However, little is known about its utility in pancreatic cancer. Plasma IGFBP2 levels were determined using enzyme-linked immunosorbent assay in 75 patients with pancreatic ductal adenocarcinoma (PDAC), 73 matched healthy controls, and 17 chronic pancreatitis patients. Our results showed that the plasma IGFPB2 level was significantly higher in PDAC patients than in patients with chronic pancreatitis and healthy controls. At a cut-off value of 333.9 ng/mL, the specificity and sensitivity were 78.08 and 65.33%, respectively. IGFBP2 level alone did not outperform carbohydrate antigen 19-9 (CA19-9) in diagnostic accuracy, but it successfully identified 9 out of 24 PDAC patients who were misidentified by CA19-9. The combination of IGFBP2 and CA19-9 was more accurate in the detection of PDAC than CA19-9 alone. IGFBP2 was more accurate than the other in discriminating between chronic pancreatitis and PDAC. Plasma IGFBP2, rather than CA19-9, was higher in the new-onset diabetes, lymph node involvement, and distant metastasis subgroups. IGFBP2 level was notably higher in stage IV cases than in stage I/II or stage III disease. However, CA19-9 did not show a difference between stages. After adjusting for lymph node involvement and distant metastasis, plasma IGFBP2 was identified as an independent prognostic marker for PDAC. The median survival time for patients with an IGFBP2 level ≥333.9 ng/mL was significantly shorter than that for patients with an IGFBP2 level <333.9 ng/mL. Marked elevation of plasma IGFBP2 in PDAC is associated with poorer survival. IGFBP2 may be considered as a supplementary biomarker for the diagnosis and prognostic prediction in Chinese pancreatic cancer patients.

Background Chronic lateral ankle instability is a relatively frequent consequence after acute ankle sprain. In case of unsuccessful conservative treatment, surgical therapy is recommended to prevent osteoarthritis of the ankle joint. To date, different surgical methods have evolved. Yet, it remains unclear which approach reveals the best results. We hypothesized that the modified Broström–Gould procedure with suture anchor ligament fixation leads to superior postoperative results compared to the Broström–Gould procedure or the periosteal flap technique. Material and methods In a prospective study, we examined the three surgical techniques. For this purpose, we performed a matched-pair analysis with four groups according to age, sex, and body mass index: periosteal flap technique (G1), Broström–Gould procedure (G2), modified Broström–Gould procedure with suture anchor ligament fixation (G3), and a control group (G4). Results were compared with the American Orthopaedic Foot & Ankle Society (AOFAS) score, a functional analysis as well as measuring postural stability with the Biodex balance system. Results No significant differences were found between all four groups concerning AOFAS score, functional results, as well as postural stability. Conclusion All three surgical methods revealed satisfactory results. No significant differences could be detected in clinical and functional categories. The Broström–Gould method as well as the modified procedure with anchor can be recommended as surgical therapy for chronic lateral ankle instability. Additional anchors do not seem to have a significant positive impact on the results.

Background Emergence agitation (EA) is a behavioural disturbance encountered during the recovery phase of patients following general anaesthesia. It is characterised by restlessness, involuntary limb movements, and drainage tube withdrawal and may significantly harm patients and medical staff. The mechanism of EA has not been fully understood and is still a challenging subject for researchers. Methods We extracted relevant publications published between 1 January 2001 and 31 December 2023 on the Web of Science Core Collection platform. VOSviewer software was utilised to analyse the retrieved literature and predict the development trends and hotspots in the field. Results The results show that the number of publications grew annually, with China contributing the most, followed by the United States and South Korea. The co-occurrence of keywords “children,” “propofol,” “risk factors” are current research hotspots. Owing to its self-limiting and short-duration characteristics, EA lacks standardised clinical time guidelines and objective assessment tools, which may be the focus of future research in this field. Conclusions Understanding the research hotspots and the latest progress in this field, this study will help to continuously improve the clinical understanding and management of EA, and help to timely identify environmental risk factors for EA in clinical practice.

Background Most gastrointestinal polyps are asymptomatic; therefore, assessing symptoms associated with cancer and precancerous polyps is essential. Objectives The aim of this study was to study the histopathology, number, distribution, and degree of polyps’ dysplasia in terms of age, gender, and clinical presentation. Methods This study was performed on patients who underwent endoscopy from July 2015 to August 2021 in Sulaimaniyah, Iraq. Surgical pathology records of patients were analyzed for age, sex, nature of the polyps, number, site, histopathology, degree of dysplasia, resection margins and patients’ presented clinical data. Results The mean patients’ age was 51.4 ± 17.1 years, and most were males (51.9%). The most common indications for endoscopy were screening (28.62%), and the least common was weight loss (4.46%). Neoplastic polyps were common among patients with hematemesis (75%), while non-neoplastic were common among those with dyspepsia (60%). Most polyps were solitary in upper (80.8%) and lower gastrointestinal tract (GIT). Most polyps in the upper GIT were non-neoplastic (87.3%), while most lower proximal/distal GIT polyps were neoplastic. Most neoplastic polyps showed low-grade dysplasia (94.4%), and most high-grade dysplasia was a villous type (24.1%). Conclusions Initiation of the screening program is highly recommended as a facilitating method for the early detection of multiple and high-grade gastrointestinal polyps. Thus, screening programs can reduce the rate of mortality of carcinoma in this locality.

Background The pathogenesis of inflammatory bowel disease (IBD) is closely associated with the dysfunction of the intestinal epithelial barrier, leading to increased bacterial translocation, leukocyte infiltration, and mucosal injury, which may act as a pivotal or incipient event in the pathophysiology of the disorder. The primary objective of this study is to examine the key genes implicated in IBD and the perturbation of intestinal epithelial cell function. Methods The genes associated with ferroptosis were identified through the utilization of the Gene Expression Omnibus (GEO) database and the GeneCard database. Additionally, an in vitro model of IBD was established by stimulating Caco-2 cells with lipopolysaccharides (LPSs) to investigate the molecular mechanisms underlying intestinal epithelial cell dysfunction. Results We discovered evidence that establishes a connection between ferroptosis and the inflammatory responses associated with the development of IBD. This evidence suggests that IBD patients who exhibit an inflammatory response have higher expression of the acyl-CoA synthetase long-chain family member 4 (ACSL4) gene compared to IBD patients without an inflammatory response or healthy individuals. Exposure to LPS at concentrations of 1 or 10 μg/mL resulted in a significant upregulation of ferroptosis-related genes ACSL4, GPX4, and SLC7A11, as well as an increase in ferroptosis biomarkers MDA and a decrease in CAT and GSH-Px levels compared to the control group. Inhibition of ACSL4 using si-ACSL4 or rosiglitazone demonstrated protective effects against LPS-induced ferroptosis and NF-κB-mediated inflammatory response. Conclusion ACSL4 shows potential as a promising target for ferroptosis in the prevention and treatment of IBD and dysfunction of intestinal epithelial cells.

Purpose This study aimed to assess the biodistribution and bioactivity of the affibody molecular probe 99m Tc-(HE) 3 Z HER2:V2 , prepared by genetic recombination, and to investigate its potential for targeted human epidermal growth factor receptor 2 (HER2) imaging in SKOV3 ovarian cancer and MDA-MB-361 breast cancer xenografts. Methods Affibody molecules were generated through genetic recombination. The radiochemical purity of the 99m Tc-labeled HER2 affibody was determined using reverse phase high performance liquid chromatography (RP-HPLC). Evaluation of HER2 affinity in SKOV3 ovarian cancer cells and MDA-MB-361 breast cancer cells (HER2-positive) was conducted by calculating equilibrium dissociation constants. Biodistribution of the 99m Tc-labeled affibody molecular probe was assessed in Balb/c mice bearing SKOV3 tumors. Tumor targeting specificity was evaluated in Balb/c mice using SKOV3, MDA-MB-361, and AT-3 (HER2-negative) xenografts. Results Affibody (HE) 3 Z HER2:V2 , generated through recombinant gene expression, was successfully labeled with 99m Tc, achieving a radiochemical purity of (96.0 ± 1.7)% ( n = 3) as determined by RP-HPLC. This molecular probe exhibited specific binding to HER2-positive SKOV3 cells, demonstrating intense radioactive uptake. Biodistribution analysis showed rapid accumulation of 99m Tc-(HE) 3 Z HER2:V2 in HER2-positive tumors post-administration, primarily clearing through the urinary system. Single-photon emission computed tomography imaging conducted 1–3 h after intravenous injection of 99m Tc-(HE) 3 Z HER2:V2 into HER2-positive SKOV3 and MDA-MB-361 nude mouse models confirmed targeted uptake of the molecular probe by the tumors. Conclusions The molecular probe 99m Tc-(HE) 3 Z HER2:V2 developed in this study effectively targets HER2 for imaging HER2-positive SKOV3 and MDA-MB-361 xenografts in vivo . It exhibits rapid blood clearance without evident toxic effects, suggesting its potential as a valuable marker for detecting HER2 expression in tumor cells.

Background Gastric cancer (GC) is a leading cause of cancer-related morbidity and mortality globally. This meta-analysis was conducted to assess the impact of nutritional interventions on clinical outcomes in GC patients. Methods Comprehensive search was conducted across four medical databases to identify randomized controlled trials (RCTs) that examined nutritional interventions in GC patients. The outcomes assessed included hospitalization duration, nutritional status, immune function, and complications. Results A total of 11 studies were included. Enteral nutrition (EN) significantly reduce hospital stay duration compared to no nutritional intervention (SMD = −1.22, 95% CI [−1.72, −0.73], P < 0.001) and parenteral nutrition (PN) (SMD = −1.30, 95% CI [−1.78, −0.82], P < 0.001), but showed no significant difference compared to immunonutrition (IN). EN also improved nutritional status, indicated by higher albumin prealbumin levels, and improved immune function by elevating CD4+ levels (SMD = 1.09, 95% CI [0.61, 1.57], P < 0.001). However, IN showed superior effects on immunoglobulin levels (IgG and IgM). No significant differences were observed in complication rates among EN, IN, and PN interventions. Conclusion Nutritional support, particularly EN and IN, can significantly improve hospitalization outcomes, nutritional status, and immune function. Customizing interventions according to patient requirements can optimize therapeutic outcomes, highlighting the need for further research in this area.

Objective To explore the relationship between cytokines such as interferon γ (IFN-γ), interleukin-10 (IL-10), and interleukin-6 (IL-6), as well as the severity of the condition, and serum zinc (Zn) and Fe levels in children with Mycoplasma pneumoniae infection. Methods A simple random sampling method was used to select 108 children with Mycoplasma pneumoniae infection admitted to the hospital from January to December 2022 as the study subjects. Collect demographic data such as gender, age, and course of disease from all patients, as well as inflammatory cytokines (InCs) such as IFN-γ, IL-10, and IL-6, the severity of the condition, and serum trace element information such as Zn, Fe, calcium (Ca), and potassium (K) from all patients. Spearman correlation analysis was used to examine the relationship between IFN-γ, IL-10, IL-6, severity of illness, and Zn, Fe, Ca, K in children infected with Mycoplasma pneumoniae . Additionally, receiver operating characteristic (ROC) curve analysis was used to test the predictive efficacy of Zn, Fe, Ca, and K on the severity of the patient’s condition. Results This study included 108 children infected with Mycoplasma pneumoniae , of whom 6 had clinical data missing >10% and were all excluded. Finally, 102 complete clinical data were collected, with a data recovery efficiency of 94.44%. The differences in IFN-γ, IL-10, IL-6 levels, severity of the condition, as well as Zn, Fe, Ca, K levels among children of different ages, disease courses, body mass, and body temperature showed P < 0. 05. Spearman correlation analysis showed that the levels of IFN-γ, IL-10, IL-6, and severity of the condition in children with Mycoplasma pneumoniae infection were negatively correlated with Zn, Fe, Ca, and K ( ρ = −0.319 to −0.827, P < 0.05). The ROC curve analysis results indicate that Zn, Fe, Ca, and K can all be used as indicators to predict the severity of the patient’s condition (AUC = 0.710–0.759, P < 0.05). Conclusion There is a close relationship between InCs and the severity of the condition in children with Mycoplasma pneumoniae and serum trace elements. Therefore, clinical attention should be paid to monitoring the serum trace element levels of children, and reasonable measures should be taken to regulate them to accelerate the progress of disease treatment.

Background Paraquat (PQ) is a frequently used herbicide with neurotoxic effects after acute or chronic exposure. Although in vitro evidence supports the PQ toxicity to dopamine cells, its in vivo effects (especially the chronic exposure) remain ambiguous. In this study, we investigated the effect of chronic PQ exposure on the blood–brain barrier (BBB) damage and the underlying mechanisms. Methods Adult male Sprague Dawley rats and primary human brain microvascular endothelial (PHBME) cells were exposed to PQ as the animal and cell models. Evans Blue staining and hematoxylin & eosin staining were conducted to examine the BBB and brain tissue damages. The inflammatory cytokines were quantified via enzyme linked immunosorbent assay. The changes of PI3K/AKT signaling pathway were detected by western blot. Results PQ exposure can cause significant pathological lesions in the brain tissues and the BBB. IL-6 and reactive oxygen species levels were found to be significantly upregulated after PQ exposure in both the animal and cell models. PQ treatment could arrest the cell proliferation and migration in PHBME cells. PQ treatment promoted the phosphorylation of PI3K and AKT, and the application of PI3K inhibitor could attenuate PQ-induced IL-6 production, oxidative stress, BBB disruption, and brain tissue damage. Conclusion Our study demonstrated that chronic PQ exposure could impair the BBB function and induce brain tissue damage. The overactivation of the PI3K/AKT pathway, consequent upregulation of IL-6 production, and increased oxidative stress appear to mediate the inflammatory damage resulting from PQ exposure.

Background The pathogenesis of cognitive impairment (CI) in coronary artery disease (CAD) patients is still unclear and numerous influence factors could affect the CI status. The current studies suggest that sleep quality and behavior pattern are significant influence factors associated with CAD susceptibility. Methods A total of 223 participants including 90 CAD patients with CI and 133 controls were enrolled into this retrospective study. Demographic information, laboratory test results, clinical diagnostic data, and questionnaire survey were collected to recognize the influencing factors of CI in CAD patients. Appropriate statistical methods are used to analyze these collected data. Results Univariate analysis results of demographic information, laboratory test results, and questionnaire survey data revealed that the differences in fatigue symptom, age, HDL, TG, and sleep quality were statistically significant ( p = 0.006, p = 0.000, p = 0.019, p = 0.028, and p = 0.037, respectively). Logistic regression analysis showed that age, fatigue, and sleep quality were the influence factors for CI in CAD population ( p = 0.000, p = 0.035, and p = 0.017). Conclusions Sleep quality, fatigue, and age were associated with the increased susceptibility of CI in CAD patients. Both CI state and its related factors were involved in the pathological process of CAD, these findings could offer additional information for the prevention and control of CAD.

This study aimed to elucidate the effects and potential mechanisms of dioscin on chronic prostatitis (CP) in vivo and in vitro . CP models were constructed in vivo and in vitro and treated with different concentrations of dioscin. Hematoxylin and eosin staining was used to investigate the morphology of the prostate tissues. The concentration of inflammatory factors in prostate tissues was determined by enzyme-linked immunosorbent assay. The release of reactive oxygen species, malondialdehyde, superoxide dismutase, and catalase was measured using detection kits. P69 cell proliferation was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. Furthermore, the activity of the TLR4/NF-κB signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction or Western blot assay. Histopathological data suggested that dioscin exerted protective effects against prostate morphological changes. Dioscin inhibits inflammatory cytokines and oxidative stress (OS) in prostate tissues in a concentration-dependent manner. Moreover, dioscin notably inhibited the activation of the TLR4/NF-κB signaling pathway in CP rats. In vitro , dioscin remarkably reduced lipopolysaccharide-induced P69 proliferation, inflammation, OS, and TLR4/NF-κB pathway activation in a dose-dependent manner. In conclusion, dioscin exerts a protective effect in CP by decreasing the inflammatory response and OS through the TLR4/NF-κB pathways. Our findings provide a novel latent therapy for dioscin for the treatment and prevention of CP.

Background Sporadic thoracic aortic aneurysm and dissection (sTAAD) is a complicated vascular disease with a high mortality rate. And its genetic basis has not been fully explored. Method Here, 122 sTAAD patients and 98 healthy individuals were recruited, and 10 single nucleotide polymorphisms were selected and analyzed (FBN1 rs10519177, rs1036477, rs2118181, MYH11 rs115364997, rs117593370, TGFβ1 rs1800469, TGFβ2 rs900, TGFβR2 rs764522, rs1036095, and rs6785385). Moreover, multiple logistic regression analysis was used to evaluate gene–environment interactions. Results We identified that TGFβR2 rs1036095 dominant model CC + CG genotype (GT) ( P = 0.004) may be a factor of increased risk of sTAAD, especially for women. FBN1 rs1036477 recessive model AA GT ( P = 0.009) and FBN1 rs2118181 dominant model CC + CT GT ( P = 0.009) were correlated to an increased death rate in sTAAD men patients. Gene–environment interactions indicated TGFβR2 rs1036095 dominant model (CC + CG)/GG to be a higher-risk factor for sTAAD (odds ratio = 3.255; 95% confidence interval: 1.324–8.000, P = 0.01). Conclusions TGFβR2 rs1036095, FBN1 rs1036477, and FBN1 rs2118181 were identified as factors of increased risk of sTAAD. Gene–environment interactions were associated with the risk of sTAAD.

Objective To investigate the effect of three-dimensional (3D) reconstruction-assisted cognitive fusion in targeted prostate biopsy. Results There was no significant difference in the detection rate of prostate cancer (PCa) between targeted biopsy and systematic biopsy, and there was significant difference in the detection rate of clinically significant prostate cancer (csPCa) between targeted biopsy and systematic biopsy. In the low prostate total specific antigen (tPSA) group, there was no statistically significant difference in the detection rate of prostate cancer between the two biopsy modalities. However, compared with systematic puncture, targeted puncture had a higher detection rate for csPCa and a lower detection rate for clinically insignificant prostate cancer (ciPCa), and the difference was statistically significant. In the high tPSA group, there was no significant difference in the detection rate of PCa, csPCa, and ciPCa between the two biopsy types. Single needle positive rate of targeted puncture (29.77%) was significantly higher than that of systematic puncture (10.28%). Conclusions The detection rate of csPCa in 3D reconstruction-assisted cognitive fusion targeted prostate biopsy is better than that of 12-needle systematic biopsy, which markedly improved the positive rate of prostate biopsy.

Background The efficacy of artificial neural network (ANN) models employing laboratory variables for predicting fatty liver disease (FLD) remains inadequately established. The study aimed to develop ANN models to precisely predict FLD. Methods Of 12,058 participants undergoing the initial FLD screening, 7,990 eligible participants were included. A total of 6,309 participants were divided randomly into the training (4,415 participants, 70%) and validation (1,894 participants, 30%) sets for developing prediction models. The performance of ANNs was additionally tested in the testing set (1,681 participants). The area under the receiver operating characteristic curve (AUROC) was employed to assess the models’ performance. Results The 18-variable, 11-variable, 3-variable, and 2-variable models each achieved robust FLD prediction performance, with AUROCs over 0.92, 0.91, and 0.89 in the training, validation, and testing, respectively. Although slightly inferior to the other three models in performance (AUROC ranges: 0.89–0.92 vs 0.91–0.95), the 2-variable model showed 80.3% accuracy and 89.7% positive predictive value in the testing. Incorporating age and gender increased the AUROCs of the resulting 20-variable, 13-variable, 5-variable, and 4-variable models each to over 0.93, 0.92, and 0.91 in the training, validation, and testing, respectively. Conclusions Implementation of the ANN models could effectively predict FLD, with enhanced predictive performance via the inclusion of age and gender.

Metastasis significantly contributes to the poor prognosis of advanced nasopharyngeal carcinoma (NPC). Our prior studies have demonstrated a decrease in BIRC5-206 expression in NPC, which promotes disease progression. However, the role of BIRC5-206 in the invasion and metastasis of NPC has not been fully elucidated. In this study, our objective was to explore the biological function and underlying mechanisms of BIRC5-206 in NPC. Additionally, we established an NPC mouse model of lung invasiveness using C666 cells to assess the impact of BIRC5-206 on NPC metastasis. Our results revealed that silencing BIRC5-206 inhibited apoptosis and enhanced the invasion of NPC cells, whereas its overexpression reversed these effects. Moreover, decreased BIRC5-206 expression significantly increased N-cadherin and Vimentin expression while reducing E-cadherin and occludin levels, both in vivo and in vitro . Additionally, silencing BIRC5-206 markedly augmented the formation of invasive foci in lung tissues. Rescue experiments further confirmed that decreased BIRC5-206 expression facilitates NPC metastasis via modulation of the miR-145-5p/CD40 signaling pathway. In summary, our study suggests that BIRC5-206 may serve as a potential prognostic biomarker and therapeutic target in the diagnosis and treatment of NPC.

Background Sepsis triggers myocardial injury and dysfunction, leading to a high mortality rate in patients. Cardiomyocyte apoptosis plays a positive regulatory role in septic myocardial injury and dysfunction. However, the mechanism is unclear. Methods Bioinformatics analysis was used to identify differentially expressed genes in septic mice heart and validate key genes and pathways. The correlation of protein–protein and protein–pathway was analyzed. Sequentially, the cecal ligament and puncture (CLP) was used to induce septic mice, followed by Serpine1 inhibitor treatment. Finally, the regulatory relationship of Yes-associated protein1 (YAP1), Serpine1, and caspase-3 was verified in LPS-exposed mouse cardiomyocytes. Results Bioinformatic analysis found that Serpine1 expression is decreased in septic mice heart tissue and closely related to the HIPPO signaling pathway, while YAP1 is negatively correlated with apoptosis. In vivo , CLP induced a reduction of survival rate, cardiac dysfunction, and an increase in Serpine1 and Cleaved Caspase-3 expression, which could be reversed by a Serpine1 inhibitor. In vitro , LPS induced the mouse cardiomyocytes apoptosis, which could be reversed by Serpine1 inhibitor. Silencing YAP1 and Serpine1 reversed the LPS-induced increase in Serpine1 and Cleaved Caspase-3 expression, but silencing Serpine1 did not affect the LPS-induced YAP1 expression. Conclusion Sepsis induced mouse cardiomyocytes apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway.

Objective The aim of this study was to investigate iron status and iron deficiency in incident continuous ambulatory peritoneal dialysis (CAPD) patients and identify influencing factors. Methods Patients with end-stage renal disease were enrolled. Clinical data of iron metabolism and biochemical and dialysis parameters during the first peritoneal dialysis evaluation were collected. Serum ferritin (SF) and transferrin saturation (TSAT) levels were evaluated, and independent influencing factors were identified by correlation and regression analyses. Results Of 1,128 adult CAPD patients, 41.2% had iron deficiency (ID), 15.7% had absolute iron deficiency, and 8.2% had functional iron deficiency. The average SF level was (276.8 ± 277.9) μg/L, and iron saturation was (29.8 ± 12.7)%. Additionally, 50.2 and 69.3% of patients reached targets in SF level and iron saturation recommended by the Chinese Society of Nephrology. SF level and TSAT were not correlated with estimated glomerular filtration rate, whereas negatively correlated with platelet count and inflammatory factors. Low platelet count, presence of diabetes mellitus and high interleukin 6 levels were independent factors of lower TSAT. Conclusions ID is common in patients with CAPD. Women and those with thrombocytopenia, diabetes, and inflammation are at higher risk for iron storage or reduced iron utilization. In the initial CAPD stage, a reasonable iron supplement strategy may be established for CAPD patients with high-risk factors.

Purpose Gustilo IIIB/C injuries are common for tibia diaphysis fractures with high rates of nonunion, osteomyelitis, and amputation. However, the managements on tibial Gustilo IIIB/C injuries are still controversial and individual. The aim of this study is to introduce the tibial periosteum flap combined with autologous bone grafting to treat Gustilo-IIIB/IIIC injuries. Methods Sixteen Gustilo type IIIB/C tibial fracture patients who underwent tibial periosteum flaps with autologous bone grafting surgeries were retrospectively studied. In the first stage, the wound was treated with debridement and the fracture was reduced and fixed with an external fixator. After covering with vacuum sealing drainage for 7 days, the wound areas were repaired by flaps. When the flaps survived and external fixators were removed, the tibial periosteum flaps were taken with autologous bone grafting for bone defects. Results The tibia fractures were comminuted fractures with mean size of segment bone defects 3.1 ± 1.3 cm. All the flaps survived and the wound healed in the first stage after an average of 1.5 ± 0.6 months. The mean size of the flap was 13.2 ± 2.8 cm × 7.3 ± 3.1 cm. All the autografts healed in 4.5 ± 0.7 months without infection and malunion. There was no pain in the affected limb. The weight-bearing and walking function were restored. Conclusion Tibial periosteum flap combined with autologous bone grafting is effective to treat bone–skin defect of leg with Gustilo-IIIB/IIIC injury.

To observe the effect of intravenous general anesthesia under nasopharyngeal airway-assisted ventilation on patients undergoing ureteroscopic holmium laser lithotripsy. One hundred and twenty patients who underwent ureteroscopic holmium laser lithotripsy in our hospital were selected and randomly divided into nasopharyngeal airway group (research group) and laryngeal mask group (control group). These patients, respectively, received intravenous anesthesia under nasopharyngeal airway and laryngeal mask-assisted ventilation. The following evaluation indexes were compared and analyzed between the two groups, including anesthetic effect, hemodynamics, stress response, postoperative recovery, adverse reactions, etc. There were no significant differences in Visual Analog Scale, hemodynamics, and stress response between the two groups at each time point ( P > 0.05 ). There were no significant differences in residence time and postoperative recovery time between the two groups ( P > 0.05). The difference in airway establishment time between the two groups was statistically significant ( P < 0.05), and cases with blood in the research group was significantly lower than those in the control group ( P < 0.05). Patient satisfaction in research group was significantly higher than those in the control group ( P < 0.05). The clinical effect of intravenous general anesthesia under nasopharyngeal airway-assisted ventilation in ureteroscopic holmium laser lithotripsy is significant, which helps to stabilize patients’ hemodynamics, reduce their stress response and adverse reactions, and improve the satisfaction rate of patient.

The oncogenic role of long intergenic noncoding RNA for IGF2BP2 stability (LINRIS) has been reported in colorectal cancer. This research aimed to study its potential involvement in gastric cancer (GC). In this study, paired GC and non-tumor tissues were obtained from 64 GC patients, and the levels of LINRIS, mature microRNA-34a (miR-34a), and miR-34a precursor in these tissues were measured with RT-qPCR. Linear regression was used to analyze their correlations. The role of LINRIS overexpression and siRNA silencing in regulating the maturation of miR-34a was analyzed by RT-qPCR. Cell apoptosis was studied with flow cytometry. It was observed that LINRIS was overexpressed in GC and showed a negative correlation with mature miR-34a, but not miR-34a precursor. In GC cells, LINRIS siRNA silencing upregulated mature miR-34a level, but not miR-34a precursor level. LINRIS overexpression downregulated miR-34a level. Cell apoptosis analysis showed that LINRIS siRNA silencing and miR-34a overexpression promoted GC cell apoptosis and suppressed cell migration and invasion, while LINRIS overexpression suppressed cell apoptosis and enhanced cell migration and invasion. In addition, the effect of LINRIS overexpression was reversed by miR-34a overexpression. Therefore, LINRIS siRNA silencing in GC may promote cell apoptosis by promoting miR-34a maturation.

Objective This study investigated the effect of forkhead box M1 (FOXM1) and Aurora kinase B (AURKB) on the epidermal function of keratinocytes. Methods Bioinformatics analysis was used to analyze the co-expression network of FOXM1 and its correlation with AURKB. The expression of FOXM1 and AURKB in tissues and cells was detected by immunofluorescence and real-time quantitative polymerase chain reaction, respectively. HaCaT cells were transfected with si-FOXM1 to knock down FOXM1. Cell proliferation was detected by cell counting kit-8 assay. Cell migration was detected by scratch assay. Cell invasion was detected by the Transwell invasion assay. Cell apoptosis and cell cycle were detected by flow cytometry. Results FOXM1 and AURKB were positively correlated and highly expressed in psoriatic lesions. After transfection of si-FOXM1, the expression levels of FOXM1 and AURKB genes significantly decreased. The proliferation of HaCaT cells decreased, the apoptosis rate increased significantly, and the proportion of cells in the G1 phase increased significantly, while the proportion of cells in the S phase decreased significantly. The scratch closure of HaCaT cells was reduced, and the number of cell invasions decreased significantly. Conclusion FOXM1 and AURKB may affect the progression of psoriasis by regulating the proliferation, cell cycle, migration, and invasion of keratinocytes.

It is during childhood that eating behaviors begin to form, with parents being the main agents in this process. Parents have eating habits that shape their children’s diet, both in terms of variety and quantity of food eaten. The aim is to analyze sociodemographic factors related to parental control over their children’s diet. Descriptive-correlational and cross-sectional study, with a sample of 46 parents of preschool children. An online questionnaire was used to collect data, with data processing carried out using SPSS, using descriptive and inferential statistics. The majority of respondents were mothers (89.1%), belonged to the 20–44 age group (89.1%), and were married (89.1%). The mean of the subscales of the children’s food questionnaire food restriction, pressure to eat, and monitoring was 3.266 ± 0.570, 3.109 ± 1.206, and 4.268 ± 0.848, respectively. The mean rank score for the food restriction subscale differed significantly between parents with different age groups (Mann–Whitney: p < 0.014), with the 45–64 age group having the highest mean rank, i.e., they restricted their children more in food. The age group is a factor related to food restriction, making it essential to take a closer look at the parents of that age group, during the health education process.

Objectives Autologous hematopoietic stem cell transplantation (auto-HSCT) is considered optional consolidation therapy especially for relapsed/refractory extranodal NK/T-cell lymphoma (ENKL), but its applications to newly diagnosed advanced-stage ENKL is currently limited. Methods We collected 51 cases of newly diagnosed advanced-stage ENKL patients, including 26 with auto-HSCT and 25 with chemotherapy rather than HSCT, from our hospital between 2014/01 and 2023/12. We summarized the patients’ characteristics, conducted survival analysis of the 51 cases, and analyzed the potential benefits of auto-HSCT to ENKL patients. Results It shows that after a median follow-up time of 39 months, the estimated 5-year overall survival (OS) of the 51 newly diagnosed advanced-stage ENKL patients is 73.4%, and their estimated 5-year progression-free survival (PFS) is 73.4%. For patients receiving auto-HSCT, the 5-year OS (91.7%) and PFS (91.0%) are significantly different from those of patients receiving chemotherapy without HSCT (OS 53.3%, PFS 54.5%) ( p < 0.05). Univariate and multivariate analysis results suggest that only the l -asparaginase usage in chemotherapy showed significant impact on the OS, and none of concerned factors showed significant impact on the PFS. Conclusions Auto-HSCT is indeed an option to newly diagnosed advanced-stage ENKL, but further studies are still required for more strict disease management.

Objective The aim of this study was to investigate the significance of colposcopy in diagnosing cervical lesions when negative cervical cytology is combined with positive human papillomavirus (HPV). Methods Overall, 370 patients with cervical epithelial lesions who had negative cervical fluid-based cytology combined with positive HPV results were selected and analysed for severity of cervical lesions and HPV distribution. Results Among the patients with cervical lesions, 242 had a single HPV infection, and 128 cases had multiple infections. No significant difference was found between HPV single infection and multiple infections in both groups of patients with cervical lesions ( P > 0.05). Furthermore, 137 had non-HPV 16 and 18, accounting for 37.30% of all the patients with cervical lesions. Among them, HPV 52, 58, and 33 infections were the most common at 38.69, 30.66 and 29.20%, respectively – significantly higher than other high-risk HPV types ( P < 0.05). Conclusion High-risk HPV testing is crucial in patients with negative cervical fluid-based cytology combined with positive HPV results. Patients with HPV 16 and 18 and those with simple HPV 52, 58, and 33 infections should undergo timely colposcopy.

Research indicates that hypoxic pulmonary hypertension (HPH) potentially stimulates the sympathetic nervous system, which may increase norepinephrine (NE) release and cause excessive Ca 2+ influx into pulmonary artery smooth muscle cells (PASMCs), leading to calcium overload and abnormal PASMC proliferation, factors closely associated with pulmonary vascular remodeling (PVR). This study investigates the potential mechanisms underlying echinacoside (ECH) treatment in HPH. Method In the in vitro experiment, NE-induced PASMCs were used to simulate HPH-induced PASMCs’ calcium overload and abnormal proliferation. Postincubation with ECH, [Ca 2+ ] cyt changes were detected using Fluo-4 AM. Flow cytometry was employed to ascertain ECH’s inhibitory effect on PASMCs proliferation. For in vivo experiments, rats were exposed to a hypoxic and low-pressure oxygen environment to establish the HPH model. Post-ECH treatment, hematoxylin and eosin (HE) staining was conducted to assess PVR, and western blot analysis was used to examine protein expression in the lung tissues of the different groups. Results ECH was observed to inhibit [Ca 2+ ] cyt increase in NE-induced PASMCs in a concentration-dependent manner, effectively reducing abnormal cell proliferation. It also reduced the expression of Transient receptor potential channel (TRPC) 1 (TRPC1), TRPC4, TRPC6, and calmodulin in PASMCs. In vivo studies demonstrated that ECH lowered the expression of these proteins in lung tissues of HPH rats, significantly decreased mean pulmonary artery pressure, and mitigated PVR.

Background Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, holds a role in cancer, inflammation, and immunity. However, its specific function in the nephropathy and high-glucose-induced human renal tubular epithelial cells (HK-2) injury in diabetic db/db mice is not clear. Methods This study explored the expression characteristics of ADAR1 in proximal renal tubular cells of diabetic db/db mice, examining its function in the mechanism of high-glucose-induced HK-2 cell injury. Furthermore, it elucidated the molecular mechanism underlying the protective effect of ADAR1, the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mammalian target of the rapamycin (mTOR) signaling. We observed a decrease in ADAR1 expression in proximal tubular cells of diabetic db/db mice, accompanied by an increase in the expression of inflammation-related markers (PI3K/AKT/mTOR). Results We constructed and validated ADAR1-overexpression plasmids and used an ADAR1 inhibitor (8-azaadenosine) to carry out cell experiments. The upregulation of ADAR1 expression alleviated high-glucose-induced endoplasmic reticulum stress, reduced HK-2 cell apoptosis, and reduced the expression of inflammation-related indicators (PI3K/AKT/mTOR). Conclusion Taken together, the pivotal roles of ADAR1 in the progression of proximal renal tubulopathy and the mechanism of high-glucose-induced HK-2 injury in diabetic db/db mice suggest that ADAR1 may be a potential key factor in slowing the progression of diabetic kidney disease.

Objectives The aim of this study was to determine the association between insulin glargine usage and the potential increase in cancer risk among the Lithuanian population diagnosed with type 2 diabetes mellitus (T2DM). Methods A retrospective cohort study was conducted. The cohort of insulin users was established by identifying all male and female patients diagnosed with T2DM, as recorded in the National Health Insurance Fund database between 1 January 2000 and 31 December 2012. The risk of cancer among insulin glargine users was compared with the risk in non-glargine insulin users. Cox proportional hazard models were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI). Results The overall cancer risk for all sites combined showed no significant difference (HR 0.84, 95% CI 0.67–1.05). Although a general decrease in the risk of cancers was observed at most sites for glargine users, the use of insulin glargine was associated with a non-significant increase in the risk of mouth and pharynx, stomach, non-melanoma skin, breast, cervical, ovarian, and central nervous system cancers. There was a tendency for a lower risk of colon, rectum, rectosigmoid, and anus cancer among glargine users (HR 0.45, 95% CI 0.18–1.12, p = 0.09). Conclusions Our research contributes to the growing body of evidence showing that insulin glargine is not associated with an increased risk of all cancers or specific types of cancer.

Background Cystic echinococcosis mainly affects the liver and lungs, in which the larvae from the microvascular wall in the liver pass to the lungs and then to the blood circulation and settle in any tissue or organ. Objectives The objective of this study was to report the unusual location of hydatid cysts in infected patients in Sulaimaniyah City, Iraq. Patients and methods This retrospective case series study enrolled 13 patients. They underwent a surgical operation to excise their cyst after confirmed diagnosis with blood investigations, electrocardiogram, chest X-ray, computed tomography scan, and magnetic resonance imaging (when needed). After the operation, the cyst was confirmed with histopathological examination, and patients were advised to take an Albendazole tablet. Results Most patients were females from rural areas, with a mean age of 38.93 ± 14.4 years. Patients presented with cysts on the skin of the anterior abdominal wall, gluteal region, mesenteric area, pericardium, tibia bone meta diaphysis, right inguinal region, right thigh, skin of the anterior neck, spleen, left suprarenal gland, right breast, and the iliopsoas muscle. Conclusions The hydatid cyst can affect any body part with no site immune and often produces nonspecific symptoms.

Aim The study aimed to evaluate the sensitivity and specificity of these monitoring parameters in predicting postoperative neurological dysfunction. Methods In this study, a total of 85 patients with spinal cavernous malformations (SCMs) treated at Xuanwu Hospital, Capital Medical University, from November 2012 to August 2017 were included. During the surgical procedures, all patients underwent monitoring of motor evoked potentials (MEP) and somatosensory evoked potentials (SEP). The criteria for warning included a reduction of ≥80% in MEP amplitude and ≥50% in SEP amplitude. Results Among 85 patients, 40 (47.1%) had SCMs located in the thoracic segment, 35 (41.2%) in the cervical segment, 6 (7.1%) in the cervical thoracic segment, and 4 (4.7%) in the lumbar segment. MEP recordings were obtained from 81 patients, and the preoperative McCormick score was 1.53 ± 0.69. The sensitivity of multimodal monitoring combined with the criteria of 80% reduction in MEP amplitude and SEP was 83.9%, with a specificity of 69%, a positive predictive value of 69%, and a negative predictive value of 90.4%. Conclusion This study emphasizes the crucial role of electrophysiological monitoring, particularly MEP and SEP, during the surgical resection of SCMs. The findings demonstrate that this approach is effective in predicting and preventing postoperative neurological dysfunction, thereby improving patient outcomes.

Background Some studies have indicated a notable association between obesity and placenta accreta spectrum (PAS), while others have not reported. Hence, we performed a meta-analysis to explore the association between obesity and the risk of PAS. Methods To explore the association between obesity and PAS through observational studies, we conducted a systematic search across PubMed, Web of Science, Google scholar, and Scopus databases up to March 30, 2024. The meta-analysis utilized a random-effect model, with the quality of included studies assessed using the Newcastle–Ottawa scale. A significance level of less than 0.05 was considered statistically significant using Stata software, version 14 (StataCorp, College Station, TX, USA). Results The association between obesity and PAS risk in crude studies showed significance (1.51 [95% CI: 1.19, 1.82; I 2 = 0.0%]). However, in adjusted studies, the association was not significant (1.25 [95% CI: 0.45, 2.05; I 2 = 52.0%]). Conclusion These findings suggest that obesity has been proposed as potentially associated with a higher risk of PAS, particularly evident in crude studies. However, it is imperative to conduct prospective cohort studies with a large sample size and meticulous control of confounding variables to further elucidate this relationship.

Background Asthma is an inflammatory disease where the balance between Th1/Th2 and Th17/Treg plays a crucial role in its pathogenesis. Shikonin is used to treat a variety of autoimmune diseases due to its good anti-inflammatory activity. However, the effect and mechanism of shikonin on asthma remain unknown. Method Mice were sensitized with ovalbumin (OVA)/house dust mite (HDM) and treated with shikonin. Lung inflammation was assessed histologically and via flow cytometry. Bronchoalveolar lavage fluid (BALF) was analyzed for cell counts and cytokines. Shikonin’s impact on p-STAT3 was studied in vivo and in vitro. Results Shikonin inhibited OVA or HDM-induced inflammation and airway hyperresponsiveness. Upon treatment, a restoration of the Th1/Th2 and Th17/Treg balance was observed, evidenced by a reduction in IL-4 and IL-17A levels in BALF, alongside an elevation in interferon-gamma and IL-10. Furthermore, shikonin impeded the infiltration of eosinophils, neutrophils, macrophages, and lymphocytes into lung tissue. The observed decrease in STAT3 phosphorylation and diminished nuclear translocation of p-STAT3 confirmed that shikonin promotes the balance of Th1/Th2 and Th17/Treg by regulating airway epithelial STAT3. Conclusion Shikonin mitigates asthma symptoms through a STAT3-dependent mechanism, indicating its potential as an anti-asthmatic therapeutic agent.

Background Ischemic stroke associated with atherosclerosis is globally named atherothrombotic stroke. Presently, the underlying pathogenic genes promoting carotid atherosclerotic plaques transfer from a stable to unstable state remains elusive. This study aims to find the hub genes disturbing the stability of plaques and explore the primary cells affected by these hub genes. Methods The optimal hub genes from five datasets for unstable plaques were identified by overlapping genes derived from Boruta and LASSO algorithms. The hub genes’ expression levels in stroke patients were confirmed through RT-qPCR. Visualization of the hub genes’ expression across various cell clusters was achieved with the aid of the Seurat R package. Then, hub genes were overexpressed or knock-down by lentivirus and siRNA, respectively. The inflammatory factors in the culture medium were detected using an ELISA assay. Results Eight genes (APOD, ASXL1, COL4A5, HTR7, INF2, NSUN6, PDSS2, and RBBP7) were identified and confirmed by RT-qPCR. The prognostic model was built upon this eight-gene composite foundation, and the area under the curve was 0.98. Based on CIBERSORT findings, unstable plaques displayed a higher macrophage proportion compared to stable ones ( P < 0.05). These eight genes also correlated with infiltrated immune cells, especially macrophages. Then, according to single-cell RNA-seq analysis, we found that the eight hub genes mainly expressed in macrophages. The cellular localization of two hub genes (NSUN6 and HTR7) with high distinguishability was confirmed, and gene set enrichment analysis also clarified the possible biological pathways regulated by them. The findings from the in vitro investigation revealed that TNF-α and IL-6 were reduced in macrophages with NSUN6 overexpression or HTR7 knockdown. Conclusion Eight hub genes, especially NSUN6 and HTR7, were found to promote the progression of plaques by regulating the immune responses of macrophages.

Objectives The COVID-19 pandemic had adverse health outcomes on individuals and communities. In this cross-sectional study we evaluated the admission rates in a tertiary-level hospital during the first wave of the pandemic (March 22, 2020 to August 31, 2020). Methods We compared the indications for admission during the first wave of the pandemic to a control period prior to the lockdown (November 9, 2019 to March 22, 2020). Results Most hospital admissions during the curfew period were obstetric emergencies (46.88%), which were significantly higher than the control group (38.19%) p ≤ 0.0001. Among the obstetric emergencies, cases in active labor (65.63%) were dominant. Significant rises in car deliveries (2.46%, p ≤ 0.0001) and admissions during the second stage of labor (6.43%, p ≤ 0.001) were noted. There was also an increased rate of admissions for early pregnancy complications, induction of labor, elective obstetric cases, and medical obstetric cases. Conclusions This study demonstrates that lockdown precautions implemented had a significant impact on the rate of admissions to Maternity Hospital. The data obtained may be a used to aid in designing robust policies for future pandemics to avoid adverse health outcomes.

Temporal muscle thickness (TMT) serves as an indicator of sarcopenia and holds predictive value for various cancers. This study aims to evaluate the prognostic significance of TMT for high-grade glioma patients. A retrospective review of 172 high-grade glioma patients from January 2015 to December 2022 was conducted. TMT value was measured based on contrast-enhanced T1-weighted magnetic resonance images before surgery. Pearson analysis was used to evaluate potential correlations. Cox regression analysis was performed to evaluate overall survival for high-grade glioma patients. In our study, the cutoff value of TMT was determined as 7.4 mm. TMT value was not a significant prognostic predictor for high-grade glioma patients (hazard ratio [HR]: 1.151, 95% confidence interval [CI]: 0.9299–1.424, p = 0.196). World Health Organization (WHO) VI and high body mass index (BMI) value were significantly associated with poorer survival outcomes (HR: 2.6689, 95% CI: 1.5729–4.528, p < 0.001; HR: 1.120, 95% CI: 1.0356–1.211, p = 0.005). TMT did not show a significant association with other factors ( p > 0.05). Notably, age demonstrated a significant difference between the thicker and thinner groups ( p = 0.019). Our study revealed that WHO grade and BMI demonstrated significant prognostic value for survival outcomes. Consequently, TMT does not appear to be a significant or applicable predictor in patients with high WHO grades.

Objective This study aimed to clarify the roles and underlying mechanisms of luteolin in the progression of cerebral ischemia/reperfusion injury (CIRI). Methods A mouse model of CIRI was established using the middle cerebral artery occlusion (MCAO) method, after which luteolin was administered. Subsequently, neuronal apoptosis and pyroptosis were measured and the brain tissues of each group were subjected to RNA sequencing. Results Luteolin alleviated MCAO-induced brain infarction, apoptosis, and pyroptosis. RNA sequencing identified 3,379, 2,777, and 3,933 differentially expressed genes (DEGs) in the MCAO vs sham, MCAO vs MCAO + luteolin, and MCAO + luteolin vs sham groups, respectively. The identified DEGs showed enrichment in multiple processes, including pattern specification, forebrain development, anion transport, leukocyte migration, regulation of cell–cell adhesion, and positive regulation of the response to external stimuli, as well as the calcium, PI3K-AKT, JAK-STAT, NF-kappa B, IL-17, cAMP, cGMP-PKG, and Wnt signaling pathways. In addition, Ccl2 and Angpt2 interacted more with the other top 30 DEGs with high interaction weights. Finally, RT-qPCR results showed that MCAO induction significantly up-regulated the expression of Stoml3 , Eomes , and Ms4a15 and down-regulated Nms , Ttr , and Avpr1a ; however, luteolin could partially reverse the expression caused by MCAO. Conclusion Luteolin can alleviate brain infarction, apoptosis, and pyroptosis in CIRI, and may improve MCAO-induced CIRI by targeting the identified DEGs and their enriched pathways.

Objective To observe the efficacy of respiratory exercise in patients with tuberculous pleurisy (TBP). Methods A randomized controlled study was conducted including 146 patients diagnosed with TBP and undergoing pleural effusion drainage in Shandong Public Health Clinical Center from June 2020 to December 2022, and the patients were randomly divided into the control group and the respiratory exercise observation group. Pleural effusion drainage time, the difference of pulmonary function, and the degree of pleural hypertrophy between the two groups at 1 and 3 months after treatment were studied. Results Compared with the control group, the pleural effusion drainage time of the observation group was shortened, and there was no significant difference between the two groups in terms of lung function and the degree of pleural hypertrophy at 1 month after treatment, while the lung function indexes and the degree of pleural hypertrophy of the observation group were significantly improved compared with that of the control group at 3 months after treatment. Conclusion Respiratory exercise can shorten the drainage time of effusion in patients with TBP, and help to improve lung function and alleviate pleural hypertrophy adhesion.

Objective To explore the role of cystic fibrosis transmembrane conduction regulator (CFTR)-Epithelial sodium channel (ENaC) in spinal cord edema after spinal cord injury (SCI) and the related mechanism. Methods Lipopolysaccharide (LPS)-treated M1830 astrocytes were applied as the SCI in vitro model. Immunohistochemistry, real-time PCR, and Western blotting were utilized to detect CFTR and ENaC expression. Enzyme-linked immunosorbent assay was used to measure inflammatory cytokines including TNF-α, IL-1β, IL-6, and IL-18. Transmission electron microscope examined ultrastructure changes, while CFTR-172 or Capsazepine treatment assessed their effects on edema and inflammation. Western blot analysis was employed to evaluate the PI3K, p-PI3K, AKT, and p-AKT signaling pathways in treated cells. Results LPS-treated M1830 cells exhibited increased levels of CFTR and pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-18, alongside decreased ENaC expression and suppressed p-PI3K/PI3K and p-AKT/AKT levels. Degeneration of the myelin sheath and axons was observed in LPS-treated M1830, while changes in ultrastructural were recovered after adding CFTR-172 or Capsazepine. The level of CFTR, TNF-α, IL-1β, IL-6, and IL-18 was decreased, while the level of ENaC, p-PI3K/PI3K, and p-AKT/AKT was increased obviously in LPS-treated M1830 with CFTR-172, Capsazepine, or IGF-1. Conclusion Down-regulation of CFTR and up-regulation of ENaC can attenuate inflammation in SCI by activating the PI3K/AKT signaling pathway, highlighting a new therapeutic approach for SCI treatment. These findings address a critical gap in current SCI treatments and suggest a novel intervention strategy targeting ion channel regulation.

Objective Dysregulation of chondrogenic differentiation is associated with osteoarthritis (OA). The myokine irisin is beneficial in OA treatment; yet, the underlying mechanism is not fully understood. Long noncoding RNAs (lncRNAs) act as important regulators of chondrocyte differentiation. This study was conducted to address the role of lncRNAs in mediating irisin-induced chondrocyte differentiation. Methods We investigated the irisin-regulated lncRNA profile change in human mesenchymal stem cells (MSCs) using published whole transcriptome sequencing data. We predicted their potential targets and competitive endogenous RNA (ceRNA) prediction and analyzed their molecular functions using functional enrichment analysis. Results More differentially expressed lncRNAs (DElncRNAs) were observed in irisin-treated samples. The top irisin-induced lncRNAs were associated with OA or chondrogenic differentiation, including XIST , PAX8-AS1 , CASC15 , LINC01618 , and DLX6-AS1 . The DEGs co-expressed with DElncRNAs were enriched in skeletal system development, extracellular matrix (ECM) organization, cell adhesion, and inflammation associated pathways. Several lncRNAs likely acted as ceRNAs to regulate downstream mRNAs including ROR2 and SORBS1 in in OA or chondrogenic differentiation. Conclusions We demonstrate the global regulation of lncRNAs by irisin during chondrogenic differentiation of human MSCs. Further study is required to characterize the key irisin-regulated lncRNAs in chondrogenic differentiation

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are common X-inherited neuromuscular diseases. The genetic diagnosis has been used as the diagnostic choice for DMD/BMD. The study subjects consisted of 37 patients from Southwest China. Peripheral blood was collected for the extraction of genomic DNA. DMD mutation was sequenced using the next-generation sequencing approach. The detected mutation was validated using the multiplex ligation-dependent probe amplification or Sanger sequencing methods. Variation annotation and pathogenicity prediction were performed using the online databases. Pathogenic mutations were identified 3 splicing site, 7 single nucleotide, 1 indel, 23 deletion, and 3 duplication mutations. Novel DMD variants were discovered, including two novel splicing variations (c.1890 + 1G>T; c.1923 + 1G>A), one missense mutation (c.1946G>T), one nonsense mutation (c.7441G>T), one indel mutation (INDEL EX20), and one duplication mutation (DUP EX75-78). The current study provides mutation information of DMD for the genetic diagnosis of DMD/BMD.

Heart failure (HF) is a common cardiovascular disease that is related to systemic inflammation. This study aimed to assess the role of C-reactive protein (CRP) combined with fibrinogen-to-albumin ratio (C-FAR) on the prognosis of all-cause mortality in different types of HF. A total of 1,221 hospitalized HF patients from the First Affiliated Hospital of Kunming Medical University between January 2017 and October 2021 were retrospectively analyzed. Patients were categorized into a low C-FAR group (C-FAR < 0.69) and a high C-FAR group (C-FAR ≥ 0.69) according to the median C-FAR value. We used Kaplan–Meier plots, restricted cubic spline regression, Cox survival analyses, and time-dependent receiver operating characteristic (ROC) analyses to evaluate the prognostic role of C-FAR on all-cause mortality in different types of HF. After excluding patients lost to follow-up and those with missing data, we ultimately included 1,196 patients with HF. The Kaplan–Meier plots showed that HF patients with high C-FAR levels had a significantly greater risk of all-cause mortality. In all four Cox proportional risk models, C-FAR was an independent predictor of all-cause mortality. Based on the ROC curve, the area under the curve (AUC) for C-FAR was greater than the AUC for Lg BNP. In the subgroup analyses, patients had the highest risk of all-cause mortality when FAR ≥ 0.091 and CRP ≥ 7.470. Regardless of the type of HF, C-FAR can be a good predictor of prognosis for all-cause mortality in HF patients, and patients with high C-FAR had a significantly increased risk of death compared to those with low C-FAR.

Background This study investigated the role and mechanisms of cullin-1 (CUL1) in chronic obstructive pulmonary disease (COPD). Methods Cigarette smoke extract (CSE)-treated mouse pulmonary microvascular endothelial cells (mPMECs) and cigarette smoke inhalation (CSI)-stimulated mice were used to construct in vitro and in vivo COPD models, respectively. CUL1 expression was assessed using reverse transcriptase-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry were used to detect cell viability and apoptosis, respectively. We conducted an enzyme-linked immunosorbent assay on mPMECs and bronchoalveolar lavage fluid (BALF) to detect inflammatory factors. Reactive oxygen species, malondialdehyde, and superoxide dismutase were detected using the corresponding kits. The histological characteristics of the lung tissues were determined by hematoxylin and eosin staining. Results CUL1 expression was downregulated in COPD. CUL1 overexpression significantly promoted cell viability, reduced cell apoptosis, and inhibited inflammatory responses and oxidative stress in CSE-treated mPMECs. These changes were reversed by the p53 agonist nutlin-3. In addition, CUL1 overexpression significantly relieved COPD in mice, as confirmed by the reduced secretion of inflammatory factors in BALF, inhibited oxidative stress response, and improved lung function. Conclusion CUL1 plays a protective role in CSE-treated mPMECs and CSI-stimulated mice by inhibiting the p53 signaling pathway.

Background Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin’s lymphoma. Ferroptosis, an iron-dependent programmed cell death, is closely related to cancer prognosis. In this study, we established a model of ferroptosis related genes for prognostic evaluation of patients with MCL. Methods Using the single-cell RNA sequencing datasets GSE184031 and mRNA sequencing data GSE32018 from the Gene Expression Omnibus, we identified 139 ferroptosis-related genes in MCL. Next a prognostic model was constructed by Cox regression and Least absolute selection and shrinkage Operator regression analysis. Finally, we used CIBERSORT to analyze the immune microenvironment and the “oncoPredict” package to predict potential drugs. Results In our model, the prognosis of MCL patients was assessed by risk scoring using 7 genes ANXA1, IL1B, YBX1, CCND1, MS4A1, MFHAS1, and RILPL2. The patients were divided into high-risk and low-risk groups based on our model, and the high-risk patients had inferior overall survival. Finally, according to our model and computational drug sensitivity analysis, four small molecule compounds, BMS-754807, SB216763, Doramapimod, and Trametinib, were identified as potential therapeutic agents for patients with MCL. Conclusion In summary, we provide a prognostic model with ferroptosis-related gene signature for MCL. This study provides a prognostic model with ferroptosis-related gene signature for MCL. The results show that the model helps predict prognosis in MCL.

Objective The aim of this study was to observe the effect of nasal high-flow humidification oxygen therapy on choking reactions and related respiratory and hemodynamic effects in elderly patients undergoing fiberoptic bronchoscopy. Methods A total of 126 elderly patients aged 65–80 years who underwent painless fiberoptic bronchoscopy from March 2021 to December 2021 were randomly divided into two groups. Results The pulse oxygen saturation at T1 and T2 time points in the experimental group was higher than that in the control group ( P < 0.05), and the average arterial pressure was slightly lower than that in the control group, but there was no statistical significance. In the experimental group, the total dosage of propofol and sufentanil increased, the microscopic examination time shortened, the choking reaction decreased significantly( P < 0.05), and the total incidence of hypoxemia decreased ( P < 0.05). Conclusion The application of nasal high-flow humidification oxygen therapy in elderly painless fiberoptic bronchoscopy improves the oxygenation ability of patients increases the use of narcotic drugs, does not have a great impact on hemodynamics, reduces choking reaction, and is more conducive to the operation of endoscopy doctors.

Background Prader-Willi Syndrome (PWS) is a rare disorder that was initially documented by Prader and Willi in 1956. Despite significant advancements in the understanding of PWS over recent decades, no bibliometric studies have been reported on this field. We aimed to analyze and explore the research trends and hotspots of PWS using a bibliometric analysis to understand the future development of basic and clinical research. Methods The literature regarding PWS was retrieved from the Web of Science Core Collection Science Citation Index Expanded (SCI-Expanded) database. Data were extracted from the articles or review articles, and analyzed using CiteSpace and VOSviewer software. Results A total of 1,895 related studies have been published in 64 countries or regions. The United States has published the most articles, followed by the United Kingdom, Italy, Netherlands, and France. University of Florida (The United States), University of Kansas (The United States), University of Alberta (Canada), University of Cambridge (the United Kingdom), and Dutch Growth Research Foundation (Netherlands) were the top five most productive institutions. Butler, Merlin G. and his colleagues have made the most outstanding contributions in the field of PWS research. Keyword co-occurrence analysis showed that genomic imprinting, uniparental disomy, obesity, hyperphagia, hypothalamus, growth hormone treatment, and ghrelin appeared with the higher frequency. Furthermore, oxytocin, magel2, and management were the latest bursts keywords. Conclusion Our findings indicated that genetic mechanism, diagnose, and emerging therapies will be the hotspots and frontiers in PWS research.

Observational studies have shown an association between childhood sunburn occasions (CSOs) and melanoma in situ (MIS). However, these studies have shown contradictory results. Here, we used a two-sample Mendelian randomization (MR) method to make a causal inference between CSOs and melanoma at the genetic level. Based on the publicly available genome-wide association study summary data, including childhood sunburn ( n = 346,955) and MIS ( n = 218,792), the inverse-variance weighted (IVW) method of the random effects model was used, supplemented by the MR-Egger method, the weighted median method, and the weighted mode method. IVW results showed a 2.58-fold increased risk of melanoma development for each standard deviation increase in CSOs (odds ratio [OR] = 3.58; 95% confidence interval [CI]: 1.68–7.64; P = 1.00 × 10 −3 ), with the MR-Egger (OR = 4.76, 95% CI: 1.65–13.75, P = 5.60 × 10 −3 ), weighted median (OR = 4.89, 95% CI: 1.62–14.76, P = 4.90 × 10 −3 ), and weighted mode (OR = 6.26, 95% CI: 2.49–15.77, P = 3.00 × 10 −4 ) supporting the results. Furthermore, both the funnel plot and the MR-Egger intercepts showed the absence of directional pleiotropy between childhood sunburn and MIS. Our study confirmed that CSOs increase the risk of melanoma development.

Objective To explore the role of oxidative stress on glycogen synthase kinase-3 in lymphocytes of diabetes mellitus (DM) patients complicated with cerebral infarction (CI). Materials and methods A total of 186 DM patients were enrolled according to the inclusion criteria and exclusion criteria, including 89 DM patients alone (DM group) and 97 DM patients with CI (DM + CI) group. Eighty-one patients with CI were selected as the CI group, and 80 normal subjects over 50 years were selected as the control group. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, and malondialdehyde (MDA) content in serum were determined by colorimetric assays. Phosphorylation of GSK-3β was measured by enzyme-linked immunosorbent assay. Results (1) Compared with the control group, the SOD and GSH-Px activities in the DM group and DM + CI group were decreased, accompanied by higher MDA content. Furthermore, phosphorylation of GSK-3β was decreased. (2) In the DM + CI group, SOD activity was decreased on days 7 and 10 and month 3 compared to the CI group and was decreased on day 7 compared to the DM group. MDA content was increased from day 0 to month 3 compared to the CI group. On days 1, 7, and 10, GSH-Px activity was lower than the DM group, and on day 10 and month 3, it was lower than the CI group. Phosphorylation of GSK-3β was decreased on days 7 and 10 compared to the DM group and was decreased from day 1 to month 3 compared to the CI group. Conclusion In the present study, we demonstrated that the oxidative stress in peripheral lymphocytes of DM patients complicated with CI was stronger, and the GSK-3 activity was higher. It suggested that oxidative stress might enhance the GSK-3 activity, which might provide a diagnostic and therapeutic approach for DM complicated with CI, and targeting GSK-3 is a promising therapeutic target for the treatment of type 2 diabetes and its complications.

Background Septic shock is a clinical syndrome characterized by acute circulatory disturbance. Stroke is an acute cerebrovascular disease caused by brain tissue damage. However, the relationship of COX6C and NDUFB3 to them is unclear. Method The stroke dataset GSE58294 and the septic shock dataset GSE15491 were downloaded from the gene expression omnibus database. Screening of differentially expressed genes (DEGs), weighted gene co-expression network analysis, construction and analysis of protein–protein interaction network, functional enrichment analysis, gene set enrichment analysis, immune infiltration analysis, and comparative toxicogenomics database (CTD) analysis were performed. Gene expression heat map was drawn. TargetScan screened miRNAs regulating central DEGs. Results A total of 664 DEGs were obtained. Gene ontology analysis showed that they were mainly enriched in leukocyte activation, intracellular vesicle, neutrophil activation, and cytokine receptor activity. According to Kyoto Encyclopedia of Genes and Genomes analysis, they are mainly enriched in metabolic pathways, phagosomes, and Staphylococcus aureus infection. Core genes (UQCRQ, USMG5 [ATP5MD], COX6C, NDUFB3, ATP5L [ATP5MG], COX7C, NDUFA1, NDUFA4) were highly expressed in septic shock and stroke samples. CTD analysis found that eight core genes are associated with liver enlargement, inflammation, proliferation, fibrosis, and necrosis. Conclusion COX6C and NDUFB3 genes are highly expressed in septic shock and stroke. The higher the COX6C and NDUFB3 genes, the worse the prognosis.

Background High body mass index (BMI) is a significant risk factor for non-communicable diseases; however, its impact on disease burden in China remains understudied. This study aimed to analyze trends in the burden of type 2 diabetes mellitus (T2DM), stroke, and hypertensive heart disease (HHD) attributable to high BMI in China from 1990 to 2019. Methods We utilized data from the Global Burden of Disease 2019 study, quantifying disease burden through years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). Joinpoint regression analysis was employed to determine temporal trends. Results The study revealed distinct gender-specific temporal trends. Men exhibited a consistent increase in disease burden across all three conditions. Women showed more nuanced patterns: a gradual rise in T2DM burden, an inverted U-shaped trend for stroke, and a U-shaped trend for HHD in terms of age-standardized DALYs. Age-specific analysis demonstrated that the burden of T2DM and stroke peaked in the 70–74-year age group, whereas HHD-related DALYs continued to increase with advancing age. Conclusions Our findings underscore the need for tailored obesity prevention and management strategies in Chinese healthcare settings, emphasizing early screening and intervention for high BMI, particularly in middle-aged and older adults.

Background Hyperoxia-induced injury is a well-recognized cause of bronchopulmonary dysplasia (BPD). Existing research studies have not well elucidated the exact mechanisms underlying hyperoxia-induced cellular damage. This study examines the involvement of the P2X7 receptor (P2X7R) in hyperoxia-induced damage to human pulmonary microvascular endothelial cells (HPMVECs) via the NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) pathway. Methods HPMVECs developing hyperoxia-induced injury were subjected to the treatment of either selective inhibitors or a P2X7R/NLRP3 agonist. Western blot analysis assisted in the quantification of the levels of P2X7R, NLRP3, caspase-1, and gasdermin D (GSDMD). Additionally, the release of TNF-α, IL-1β, and IL-18 was assessed by ELISA and qRT-PCR. Results Exposure to hyperoxia diminished cell viability and escalated the levels of P2X7R, caspase-1, NLRP3, GSDMD, and N-terminal-GSDMD. This exposure notably increased the release of TNF-α, IL-1β, and IL-18 in HPMVECs. Notably, the suppression of P2X7R using the inhibitor A438079 decreased pyroptosis and inflammatory responses. Conversely, stimulation of P2X7R by 3′- O -(4-benzoylbenzoyl) adenosine 5′-triphosphate (BzATP) triggered pyroptosis, while inhibition of NLRP3 with glibenclamide ameliorated the damage induced by BzATP. Conclusions The P2X7R/NLRP3 pathway crucially affects the hyperoxia-induced inflammation and pyroptosis in HPMVECs, hinting the potential of blocking P2X7R/NLRP3-mediated pyroptotic pathway as a valuable therapeutic strategy for BPD.

Background Intrauterine adhesions (IUAs) are a significant clinical challenge, affecting reproductive health and leading to infertility or recurrent pregnancy loss. Understanding the molecular mechanisms underlying IUA prevention is crucial for developing effective treatment strategies. Objective To investigate the interaction between oviductal mucosal cells and endometrial cells and their effects on the expression of key molecules involved in embryo implantation, specifically leukemia inhibitory factor (LIF), avβ3, estrogen receptor (ER), and progesterone receptor (PR). Methods Tubal mucosa and endometrium specimens were collected from 22 patients undergoing surgical interventions. Cells were cultured alone and co-cultured at ratios of 1:1, 1:0.5, and 1:0.1. LIF, avβ3, ER, and PR expression levels were measured using real-time fluorescence quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Results Our results demonstrated that LIF expression was significantly augmented in co-culture conditions, particularly in the 1:1 ratio, compared to oviductal mucosa monoculture ( P < 0.05). Although LIF expression was also elevated in 1:0.5 and 1:0.1 co-culture ratios, these increases were not statistically significant ( P > 0.05). For avβ3, increased expression was observed in the 1:1 co-culture group ( P < 0.05), but no significant differences were detected in 1:0.5 and 1:0.1 co-culture groups. ER expression showed a downward trend in co-culture, but without statistical significance ( P > 0.05), and PR expression remained stable across all groups. Conclusion Co-culture modulates key molecules involved in embryo implantation, particularly LIF and avβ3. These findings highlight the potential roles of LIF and avβ3 in IUA prevention strategies and provide important insights for future clinical interventions. Tubal mucosal cells can not only grow in the endometrial cell microenvironment, but also the tolerance of tubal mucosal cells can be improved when they are co-cultured.

Objective The aim of this study was to assess the impact of the external oblique intercostal block (EOIB) on early postoperative pain in patients who underwent laparoscopic cholecystectomy. Methods 120 patients were divided into two groups: the EOIB group (Group E) and the control group (Group C). The assessed variables were mainly intraoperative remifentanil usage, numerical rating scale (NRS) pain scores at 0, 1, 2, 4, 6, 12, and 24 h postoperatively, cumulative fentanyl consumption within 24 h postoperatively and within the first-hour post-anesthesia care unit. Results Remifentanil consumption during surgery was significantly reduced in Group E compared to Group C. Postoperative fentanyl requirements were also lower in Group E at 1 and 24 h after surgery. Furthermore, Group E demonstrated significantly lower NRS scores at 0, 1, 2, 4, and 6 h postoperatively and a reduced need for rescue analgesia compared to Group C. However, at 12 h post-surgery, Group E’s NRS scores were slightly higher than Group C’s. Conclusion The EOIB is associated with reduced pain within the first 24 postoperative hours following laparoscopic cholecystectomy.

Background This study aims to evaluate the correlation between miRNAs and known nerve injury markers neuron-specific enolase (NSE) and S100β in ischemic stroke (IS) patients, exploring its efficacy. Methods We retrospectively analyzed 86 IS patients and 32 healthy controls. Clinical and neurological examinations were performed in the admitted patients and the severity of neurological deficits was assessed by National Institutes of Health Stroke Scale (NIHSS). Plasma extraction and serum isolation were performed on all subjects before and 2 weeks after admission. miR-142-5p in serum, and NSE and S100β contents were measured by RT-qPCR and ELISA. Results Ischemic lesions were more severe in IS patients, and NSE and S100β were abnormally elevated. miR-142-5p in the serum of IS patients was 2.85 times higher. After 2 weeks of treatment, serum miR-142-5, NSE, and S100β decreased. Patients’ serum levels of miR-142-5p were 57.5% lower. Serum miR-142-5, NSE, and S100β were lower in patients with disease improvement than in patients with poor recovery. Additionally, miR-142-5 was positively correlated with NSE ( P < 0.0001) and S100β ( P = 0.0147), and also with the NIHSS score ( P = 0.0004). Conclusions miR-142-5p, NSE, and S100β in peripheral blood (PB) of IS patients are elevated, and miR-142-5p is positively correlated with NSE and S100β.

To investigate the correlation between blood stasis syndrome and arteriopathy in immunoglobulin A nephropathy (IgAN). Wall thickness/outer vessel diameter, intimal thickness/outer vessel diameter, and medial thickness/outer vessel diameter were measured using ImageJ software. Vascular endothelial-derived growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase (ERK) 1/2, and nuclear factor kappa B (NF-κB) were detected by immunohistochemical staining. Twenty-four-hour urine protein quantification, serum creatinine, urea nitrogen, and uric acid were collected. Blood stasis syndrome and vessel scores were calculated based on Katafuchi’s grade. Intimal thickness/outer vessel diameter (0.2725 ± 0.0932 μm), medial thickness/outer vessel diameter (0.2747 ± 0.1139 μm), and wall thickness/outer vessel diameter (0.6136 ± 0.1120 μm) were the largest in IgAN with arteriopathy group. VEGF (0.35 ± 0.90), MMP-9 (0.38 ± 0.12), PCNA (0.43 ± 0.12), ERK1/2 (0.31 ± 0.11), and NF-κB (0.37 ± 0.14) were the highest in IgAN with arteriopathy group. Intimal thickening of IgAN was moderately positively correlated with VEGF, MMP-9, PCNA, ERK1/2, and NF-κB (0.5 < r < 0.8). Medial thickening of IgAN was moderately positively correlated with PCNA and NF-κB (0.5 < r < 0.8). Wall thickening of IgAN was lowly positively correlated with VEGF and MMP-9 (0.3 < r < 0.5). Blood stasis syndrome score was associated with vessel score in IgAN with arteriopathy ( P < 0.05). Blood stasis syndrome score can assess the degree of pathological changes.

Purpose To investigate the risk factors associated with progressive kyphosis (PK) after percutaneous kyphoplasty (PKP) in osteoporotic vertebral compression fractures (OVCFs). Methods A single-center retrospective study (January 2020 to December 2022) analyzed 129 OVCF patients treated with PKP. Patients were divided into a PK group and a non-progressive kyphosis group. Clinical and radiological data were compared, and univariate and multivariate regression analyses identified independent risk factors for PK. A nomogram was then developed to predict the risk factors for PK after PKP. Results Of 129 patients, 47 (36.4%) experienced PK after PKP. Multivariate analysis identified independent risk factors for PK as preoperative kyphosis angle (OR = 1.26, P = 0.008), Type D magnetic resonance image (MRI) signal change on T2-weighted images (T2WI) (OR = 18.49, P = 0.003), black line signal (OR = 44.00, P < 0.001), intervertebral disc endplate complex (IDEC) injury (OR = 7.86, P = 0.021), and postoperative Oswestry Disability Index (ODI) score (OR = 1.18, P = 0.004). The nomogram, based on these factors, demonstrated strong discriminative performance (area under the curve = 0.953) and good calibration. Conclusions Preoperative kyphosis angle, Type D MRI signal change on T2WI, black line signal, IDEC injury, and higher postoperative ODI score are independent risk factors for PK after PKP. A nomogram based on these factors accurately predicts PK risk.

Background We aimed to assess whether neuron-specific enolase (NSE) and S100-β levels are associated with early neurological deterioration (END) in patients with acute ischemic stroke (AIS). Methods We conducted a prospective study between March 2022 and October 2023 in 286 patients with AIS. Serum NSE and S100-β levels on admission and at 24 and 48 h after stroke onset were measured using electrochemiluminescence immunoassays. Outcomes included END events within 48 h of admission and unfavorable neurological outcomes at 3 months. Results Patients with END had higher serum NSE and S100-β levels. Patients with poor prognosis had higher serum NSE and S100-β levels. Serum NSE (on admission) was an independent biomarker for END in AIS patients and for unfavorable recovery at 3 months. In addition, serum S100-β was an independent biomarker of unfavorable recovery after 3 months in patients with AIS. Conclusion Serum NSE on admission and S100-β at 48 h of stroke onset may serve as biomarkers of short-term clinical outcome in patients with AIS. Elevated serum NSE and S100-β levels may be useful tools to predict prognosis in patients with AIS.

Background Postoperative cognitive dysfunction (POCD) frequently occurs following endovascular therapy for acute ischemic stroke (AIS). Given the complexity of predicting AIS clinically, there is a pressing need to develop a preemptive prediction model and investigate the impact of anesthesia depth on AIS. Methods A total of 333 patients diagnosed with AIS were included in the study, comprising individuals with non-POCD ( n = 232) or POCD ( n = 101). Univariate and multivariate logistic regression analyses were utilized to examine the independent risk factors associated with POCD. A calibration, decision curve analysis, and precision–recall curves were employed to assess the model’s goodness of fit. Results Multivariate regression analysis identified two inflammatory indicators, high-sensitivity C reactive protein (hs-CRP) and systemic immune inflammatory index (SII), and three brain injury indicators, National Institute of Health Stroke Scale (NIHSS) score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble protein-100 β (S100-β), which were used to construct a nomogram model. Conclusion The composite predictive model incorporating NIHSS score, hs-CRP, SII, NT-proBNP, and S100-β demonstrated efficacy in predicting POCD following AIS. Additionally, our results suggest a potential association between depth of anesthesia, cognitive impairment, and inflammatory response in AIS patients.

Selective serotonin reuptake inhibitor correlates with decreased bone mineral density and impedes orthodontic tooth movement. The present study aimed to examine the effects of fluoxetine on osteoclast differentiation and function. Human peripheral blood mononuclear cells (hPBMCs) and murine RAW264.7 cells were cultured with RANKL to stimulate osteoclast differentiation. The resulting multinucleated cells displayed characteristics of mature osteoclasts. Fluoxetine at 0.01–1 μM did not impact cellular viability or oxidative stress. However, 10 μM fluoxetine significantly reduced clonal growth, cell viability, and increased cytotoxicity and lipid peroxidation in RAW 264.7 cells. Further, application of 0.1 μM fluoxetine potently suppressed osteoclast differentiation of both RAW264.7 and hPBMCs, with reduced osteoclast numbers and downregulation of osteoclastic genes matrix metalloproteinase-9, cathepsin K, and integrin β3 at mRNA and protein levels. Fluoxetine also disrupted F-actin ring formation essential for osteoclast resorptive function. Mechanistically, fluoxetine inhibited NF-kB signaling by reducing phosphorylation of pathway members IκBα and p65, preventing IκBα degradation and blocking p65 nuclear translocation. In conclusion, this study demonstrates fluoxetine suppressing osteoclast differentiation in association with disrupting NF-kB activation, providing insight into orthodontic treatment planning for patients taking fluoxetine.

Objective To investigate the relationship between the expression levels of serum forkhead box protein M1(FOXM1) and insulin-like growth factor 2 (IGF2) mRNA in patients with acute respiratory distress syndrome (ARDS) condition and prognosis. Methods Ninety patients with ARDS admitted to our hospital were regarded as the ARDS group, according to the prognosis, they were grouped into death group ( n = 64) and survival group ( n = 126); the control group consisted of 190 healthy individuals. Results Compared with the control group, the level of serum FOXM1 mRNA in ARDS group was obviously lower, and the level of IGF2 mRNA was higher. The serum IGF2 mRNA, serum creatinine, inhaled oxygen concentration (FiO 2 ), and mechanical ventilation time in the death group were higher than those in the control group, and the arterial oxygen partial pressure (PaO 2 ), FOXM1 mRNA, and oxygenation index (PaO 2 /FiO 2 ) were lower than those in control group. Logistic regression analysis indicated that FOXM1, IGF2, and PaO 2 /FiO 2 were significant factors influencing the prognosis and mortality in ARDS patients. Correlation analysis showed that there was a negative correlation between serum FOXM1 and IGF2 mRNA levels in patients with ARDS. Conclusion Serum FOXM1 and IGF2 mRNA in patients with ARDS are correlated with the severity and prognosis of ARDS.

Rhein is a natural anthraquinone substance extracted from Rheum palmatum L. This study aimed to evaluate Rhein’s protective effects against skin wound by in vivo and in vitro models and investigate whether its protective mechanism regulated the PI3K/AKT signaling pathway. The skin wound mice model was established and then treated with Rhein for 10 days. Hematoxylin and eosin staining and Masson’s trichrome staining were applied to assess histological changes and collagen maturity in the mice skin wound tissues. Human skin fibroblasts (HSFs) viability, migration, and invasion were detected by Cell counting kit-8 (CCK-8), scratch wound, and transwell assays respectively. Moreover, the protein expression of p-PI3K, PI3K, p-AKT, and AKT were determined by western blot assay. We found that local treatment with Rhein promoted skin wound healing and accelerated collagen maturation, compared with the Model group. In addition, Rhein promoted skin wound healing through accelerated HSF proliferation, migration, and invasion. Furthermore, Rhein remarkably enhanced p-PI3K and p-AKT expression, as well as p-PI3K/PI3K and p-AKT/AKT ratio in skin wound mice and HSF cells, suggesting that Rhein promoted skin wound healing by activating PI3K/AKT signaling pathway. In conclusion, Rhein is a promising agent for promoting wound healing of skin tissues.

Aim The World Health Organization’s recommendation of at least 150 min of physical activity per week is important for increasing the lifespan of persons with disabilities (PWDs). Methods Conduct a survival analysis to examine the relationship between physical activity and mortality using cohort data from the National Health Insurance Service in South Korea from 2017 to 2021. The survival analysis included 259,146 PWDs, with a maximum follow-up of 57 months, and adjustments for covariates, including physical activity level, comorbidities, smoking, and alcohol consumption. Results People who exercised >150 min weekly had a lower risk of death compared to those who exercised less (adjusted hazard ratio [AHR]: 0.727, 95% confidence interval [CI]: 0.674–0.784). The risk of death increased with increasing age (AHR: 1.08, 95% CI: 1.077–1.083), smokers had a higher risk of death than non-smokers (AHR: 1.487, 95% CI: 1.396–1.583), and the risk of death increased with increasing Charlson comorbidity index scores (AHR: 1.228, 95% CI: 1.22–1.237). Conclusion Even after adjusting for socioeconomic and other risk factors, PWDs who are physically inactive have a higher risk of death. Customized physical activity policies for PWDs are needed to reduce health inequities.

Cardiovascular diseases are the leading cause of mortality and morbidity globally. Clinicians must know cutaneous signs of cardiovascular disease, including petechiae, macules, purpura, lentigines, and rashes. Although cutaneous manifestations of diseases like infectious endocarditis and acute rheumatic fever are well established, there is an indispensable need to evaluate other important cardiovascular diseases accompanied by cutaneous signs. Moreover, discussing the latest management strategies in this regard is equally imperative. This review discusses distinctive skin findings that help narrow the diagnosis of cardiovascular diseases and recommendations on appropriate treatment.

Endometrial carcinoma’s (EC) etiology is complex and involves DNA repair gene polymorphisms like XRCC1-Arg399Gln and hOGG1-Ser326Cys, but their association with the disease is unclear. Following PRISMA, we conducted a systematic review and meta-analysis, collecting data from four databases. The studies needed to be population-based case–control studies examining the association between the named polymorphisms and EC. Quality was assessed with the Newcastle-Ottawa Scale. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated, and subgroup analyses were conducted based on ethnicity. Seven studies were included. Both polymorphisms were found to significantly increase EC risk, particularly in Caucasians. XRCC1-Arg399Gln showed a dominant model OR of 1.14 (95% CI: 1.01–1.29) and a homozygous model OR of 1.59 (95% CI: 1.12–2.25). The heterozygote model OR for hOGG1-Ser326Cys was 1.29 (95% CI: 1.02–1.63), and the allele OR was 1.31 (95% CI: 1.07–1.60). XRCC1-Arg399Gln and hOGG1-Ser326Cys may increase EC risk, primarily in Caucasian women, emphasizing the role of DNA repair in disease susceptibility. More extensive studies are needed to validate these findings in diverse ethnicities and investigate other DNA repair gene polymorphisms.

Studies showed that the respiratory is not the only system affected by coronavirus 2, while cardiovascular, digestive, and nervous systems, as well as essential organs such as the kidneys, can be affected by this virus. In this review, we have studied the epidemiology, clinical, and laboratory findings on COVID-19 infection renal involvement, mortality, physiopathology, remaining renal sequels after recovery, underlying renal disease, and renal injury due to its treatment. Also, protective measures for kidney injury are explained in three levels. Evidence of viral particles and genome in the urine and renal tubular cells and signs of damage such as microangiopathy, hypercoagulopathy, and fibrosis are found in COVID-19 patients. The result of this study showed, in hospitalized COVID-19 patients, that the rate of acute kidney injury (AKI) was up to 46%, with a mortality ranging from 11 to 96%. A considerable proportion of patients with AKI would remain on renal replacement therapy. Proteinuria and hematuria are observed in 87 and 75% patients, and increased Cr and glomerular filtration rate (GFR) <60 ml/min per 1.73 m 2 are observed in 29.6 and 35.3% of the patients, respectively. Remedsivir is considered to have adverse effects on GFR. COVID-19 patients need special attention to prevent AKI. Those with underlying chronic kidney disease or AKI need proper and explicit evaluation and treatment to improve their prognosis and decrease mortality, which should not be limited to the hospitalization period.

SPDL1 (spindle apparatus coiled-coil protein 1), also referred to as CCDC99, is a recently identified gene involved in cell cycle regulation. SPDL1 encodes a protein, hSpindly, which plays a critical role in the maintenance of spindle checkpoint silencing during mitosis. hSpindly coordinates microtubule attachment by promoting kinesin recruitment and mitotic checkpoint signaling. Moreover, the protein performs numerous biological functions in vivo and its aberrant expression is closely associated with abnormal neuronal development, pulmonary interstitial fibrosis, and malignant tumor development. In this review, we provide an overview of studies that reveal the characteristics of SPDL1 and of the protein encoded by it, as well as its biological and tumor-promoting functions.

Aim This study aimed to summarize case reports of adverse drug reactions (ADRs) caused by piperacillin and explore their effects on human organs in real-world settings. Method Case reports of piperacillin ADRs were collected by searching databases such as PubMed, Embase, Web of Science, CNKI, WanFang, and VIP from inception to December 2022. Results A total of 170 patients were ultimately included. The results revealed that ADRs caused by piperacillin were primarily associated with the entire body, followed by the blood system, skin and soft tissues, and the nervous system. The most frequently reported cases included anaphylactic shock, drug fever, rash, and thrombocytopenia. The most severe ADRs were identified as anaphylactic shock and bullous epidermal necrolysis. Furthermore, a comparison was made between systemic adverse reactions caused by piperacillin as a single drug and two composite preparations of piperacillin/β-lactamase inhibitor. ADRs not mentioned in the instructions included convulsions or hallucinations and Kounis syndrome (KS). Conclusion This review suggests that the most severe ADRs associated with piperacillin are toxic epidermal necrolysis and anaphylactic shock. Rare ADRs caused by piperacillin, such as myoclonic jerks, hallucinations, and KS, were identified. The most common symptom with domestic preparations of piperacillin/sulbactam and piperacillin sodium was dyspnea.

Objective In this article, the epidemiology, molecular mechanism of occurrence and development, risk factors, and treatment of diabetic microvascular complications such as diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy were discussed, providing the theoretical basis for more accurate elucidation of the pathogenesis and treatment of diabetic microvascular complications. Methods The electronic database of PubMed was searched, and retrieved papers were screened for eligibility by two independent reviewers. Data were extracted using a standardized data extraction form and the quality of included papers was assessed. Results Thirty-eight articles were included. Diabetes nephropathy, diabetes peripheral neuropathy, and diabetes retinopathy are the most common and serious microvascular complications of diabetes in clinical patients. Renin–angiotensin system blockers, beta drugs, statins, antivascular endothelial growth factor drugs, and antioxidants can inhibit the occurrence of microvascular complications in diabetes. Conclusions However, there has been no breakthrough in the treatment of diabetic microvascular complications. Therefore, prevention of diabetic microvascular complications is more important than treatment.

Autophagy, a process that isolates intracellular components and fuses them with lysosomes for degradation, plays an important cytoprotective role by eliminating harmful intracellular substances and maintaining cellular homeostasis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity for self-renewal that can give rise to a subset of tissues and therefore have potential in regenerative medicine. However, a variety of variables influence the biological activity of MSCs following their proliferation and transplantation in vitro . The regulation of autophagy in MSCs represents a possible mechanism that influences MSC differentiation properties under the right microenvironment, affecting their regenerative and therapeutic potential. However, a deeper understanding of exactly how autophagy is mobilized to function as well as clarifying the mechanisms by which autophagy promotes MSCs differentiation is still needed. Here, we review the current literature on the complex link between MSCs differentiation and autophagy induced by various extracellular or intracellular stimuli and the molecular targets that influence MSCs lineage determination, which may highlight the potential regulation of autophagy on MSCs’ therapeutic capacity, and provide a broader perspective on the clinical application of MSCs in the treatment of a wide range of diseases.

Borderline ovarian tumours (BOTs) show intriguing characteristics distinguishing them from other ovarian tumours. The aim of the systematic review was to analyse the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach. The systematic review included articles published between 2000 and 2023 in the databases: PubMed, EMBASE, and Cochrane. After a detailed analysis of the available publications, we qualified for the systematic review: 28 publications on proto-oncogenes: BRAF, KRAS, NRAS, ERBB2, and PIK3CA, 20 publications on tumour suppressor genes: BRCA1/2, ARID1A, CHEK2, PTEN, 4 on adhesion molecules: CADM1, 8 on proteins: B-catenin, claudin-1, and 5 on glycoproteins: E-Cadherin. In addition, in the further part of the systematic review, we included eight publications on microsatellite instability and three describing loss of heterozygosity in BOT. Molecular changes found in BOTs can vary on a case-by-case basis, identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. Molecular studies have contributed significantly to our understanding of BOT pathogenesis, but substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches.

Glioblastoma multiforme (GBM) is characterized by a high mortality rate, high resistance to cytotoxic chemotherapy, and radiotherapy due to its highly aggressive nature. The pathophysiology of GBM is characterized by multifarious genetic abrasions that deactivate tumor suppressor genes, induce transforming genes, and over-secretion of pro-survival genes, resulting in oncogene sustainability. Synthetic lethality is a destructive process in which the episode of a single genetic consequence is tolerable for cell survival, while co-episodes of multiple genetic consequences lead to cell death. This targeted drug approach, centered on the genetic concept of synthetic lethality, is often selective for DNA repair-deficient GBM cells with restricted toxicity to normal tissues. DNA repair pathways are key modalities in the generation, treatment, and drug resistance of cancers, as DNA damage plays a dual role as a creator of oncogenic mutations and a facilitator of cytotoxic genomic instability. Although several research advances have been made in synthetic lethality modalities for GBM therapy, no review article has summarized these therapeutic modalities. Thus, this review focuses on the innovative advances in synthetic lethality modalities for GBM therapy.

Mitochondria-derived reactive oxygen species production at a moderate physiological level plays a fundamental role in the anti-aging signaling, due to their action as redox-active sensors for the maintenance of optimal mitochondrial balance between intracellular energy status and hormetic nutrients. Iron regulatory protein dysregulation, systematically increased iron levels, mitochondrial dysfunction, and the consequent oxidative stress are recognized to underlie the pathogenesis of multiple neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Central to their pathogenesis, Nrf2 signaling dysfunction occurs with disruption of metabolic homeostasis. We highlight the potential therapeutic importance of nutritional polyphenols as substantive regulators of the Nrf2 pathway. Here, we discuss the common mechanisms targeting the Nrf2/vitagene pathway, as novel therapeutic strategies to minimize consequences of oxidative stress and neuroinflammation, generally associated to cognitive dysfunction, and demonstrate its key neuroprotective and anti-neuroinflammatory properties, summarizing pharmacotherapeutic aspects relevant to brain pathophysiology.

Parkinson’s disease (PD), characterized by tremor, slowness of movement, stiffness, and poor balance, is due to a significant loss of dopaminergic neurons in the substantia nigra pars compacta and dopaminergic nerve terminals in the striatum with deficit of dopamine. To date the mechanisms sustaining PD pathogenesis are under investigation; however, a solid body of experimental evidence involves neuroinflammation, mitochondrial dysfunction, oxidative stress, and apoptotic cell death as the crucial factors operating in the pathogenesis of PD. Nutrition is known to modulate neuroinflammatory processes implicated in the pathogenesis and progression of this neurodegenerative disorder. Consistent with this notion, the Burseraceae family, which includes the genera Boswellia and Commiphora , are attracting emerging interest in the treatment of a wide range of pathological conditions, including neuroinflammation and cognitive decline. Bioactive components present in these species have been shown to improve cognitive function and to protect neurons from degeneration in in vitro , animal, as well as clinical research. These effects are mediated through the anti-inflammatory, antiamyloidogenic, anti-apoptotic, and antioxidative properties of bioactive components. Although many studies have exploited possible therapeutic approaches, data from human studies are lacking and their neuroprotective potential makes them a promising option for preventing and treating major neurodegenerative disorders.

Osteosarcoma is a highly aggressive bone tumor primarily affecting children and adolescents. Despite advancements in treatment modalities, the prognosis for osteosarcoma patients remains poor, emphasizing the need for a deeper understanding of its underlying mechanisms. In recent years, the concept of cancer stem cells (CSCs) has emerged as a crucial factor in tumor initiation, progression, and therapy resistance. These specialized subpopulations of cells possess self-renewal capacity, tumorigenic potential, and contribute to tumor heterogeneity. Sox9, a transcription factor known for its critical role in embryonic development and tissue homeostasis, has been implicated in various malignancies, including osteosarcoma. This review aims to summarize the current knowledge regarding the role of Sox9 in CSCs in osteosarcoma and its potential implications as a prognosis and therapeutic target.

Objectives This narrative review aims to update the current evidence and offer insight into the new non-invasive ultrasound techniques used to early identify degenerative vascular changes in subjects with periodontitis and to investigate if these methodologies could be useful to identify subclinical cardiovascular disease (CVD) dysfunction in periodontitis patients and to monitor changes in CVD risk after periodontal treatment. Methods Studies examining the assessment of vascular endothelial function through the latest methodologies were analyzed. Systematic reviews, observational studies, and clinical trials in the English language were identified using PubMed, Web of Science, and Google Scholar databases with key search terms such as “periodontitis,” “endothelial dysfunction (ED),” “arterial stiffness,” and “periodontal therapy.” Results Several mechanisms are involved in the association between periodontitis and CVD. The key players are periodontal bacteria and their toxins, which can enter the circulation and infiltrate blood vessel walls. The increase in proinflammatory molecules such as interleukins and chemokines, c-reactive protein, fibrinogen, and oxidative stress also plays a decisive role. In addition, an increase in parameters of ED, arterial stiffness, and atherosclerosis, such as carotid intima-media thickness, pulse wave velocity, and flow-mediated dilatation, has been shown in periodontal patients. Conclusions The literature today agrees on the association of periodontitis and CVD and the positive role of periodontal therapy on systemic inflammatory indices and cardiovascular outcomes. Hopefully, these non-invasive methodologies could be extended to periodontal patients to provide a comprehensive understanding of the CVD-periodontitis link from the perspective of a personalized medicine approach in periodontology.

Hidden information is the key to many security issues. If there is a reliable method to determine whether someone withholds information, many issues of this type can be resolved. However, until now, no method has proven to be reliable, but technical discoveries in the field of neuroimaging have caused a surge of new research in this area. Many neuroimaging techniques can be used, but functional magnetic resonance is the newest method, and its use in extracting and evaluating information from subjects could be the most significant, given that it records brain states in parallel with current mental activity/behavior, enabling the establishment of correlational links between them. Because the brain state displayed during fMRI imaging is the dependent variable measured during stimulus/task condition manipulation, it is necessary to use fMRI data in combination with complementary criminal interrogation techniques to gather information. This could be particularly important when standard interrogational techniques are not enough in order to preserve the common good, especially in “ticking bomb” situations. In this study, we review aspects of the possibility of utilizing advanced neuroimaging in combination with criminal interrogation in cases of serious criminal acts that threaten public safety.

Objective We conducted an umbrella review focusing on maternal risk factors during pregnancy associated with neural tube defects (NTDs). Methods Our search was in databases PubMed, Scopus, and Web of Science. We specifically targeted meta-analyses examining maternal factors during pregnancy in relation to NTDs. The comparison involved assessing metrics such as odds ratio (OR) or related risk ratios reported in the included studies, as well as parameters like heterogeneity ( I ²), 95% prediction interval, small-study effects, excess significance biases, and sensitivity analysis. Results Three risk factors for fetal NTDs, namely hyperthermia with an OR of 1.92, obesity with an OR of 1.68, and passive smoking with an OR of 1.90, were classified as highly suggestive evidence (Class II). Influenza, with an OR of 3.33, was considered a risk factor with suggestive evidence (Class III). Multivitamin supplementation during pregnancy, with an OR of 0.76, and low maternal vitamin B12, with an OR of 2.41, were categorized as weak evidence (Class IV). Conclusion We identified four risk factors including hyperthermia, influenza, obesity, and passive smoking as suggestive or highly suggestive evidence for NTDs. Low maternal vitamin B12 was identified as a risk factor for NTDs, supported by weak evidence.

Rosmarinic acid is a polyphenol found in numerous fruits and vegetables, consumed in supplement form, and tested in numerous clinical trials for therapeutic applications due to its putative chemopreventive properties. Rosmarinic acid has been extensively studied at the cellular, whole animal, and molecular mechanism levels, presenting a complex array of multi-system biological effects. Rosmarinic acid-induced hormetic dose responses are widespread, occurring in numerous biological models and cell types for a broad range of endpoints. Consequently, this article provides the first assessment of rosmarinic acid-induced hormetic concentration/dose responses, their quantitative features, mechanistic foundations, extrapolative strengths/limitations, and their biomedical, clinical, and public health implications.

Background Parkinson’s disease (PD) is primarily known as a motor disorder; however, its debilitating non-motor symptoms have a significant impact on patients’ quality of life. The current standard treatment, l -DOPA, is used to relieve motor symptoms, but prolonged use is often associated with severe side effects. This creates an urgent need for effective alternatives targeting both motor and non-motor symptoms. Objectives Over the past decade, Cannabis sativa and its cannabinoids have been widely studied across various health conditions. Among these compounds, cannabidiol (CBD), a non-psychoactive component, is garnering growing interest due to its multi-targeted pleiotropic properties. This work aims to provide a comprehensive overview of CBD’s efficacy in PD. Methods This review compiles data on both motor and non-motor symptoms of PD, integrating results from preclinical animal studies and available clinical trials. Results Preclinical research has demonstrated promising results regarding CBD’s potential benefits in PD; however, the total number of clinical trials is limited (with only seven studies to date), making it difficult to draw definitive conclusions on its efficacy. Conclusions While preclinical findings suggest that CBD may have therapeutic potential in PD, the limited number of clinical trials highlights the need for further research. This review emphasizes the gaps that need to be addressed in future studies to fully understand CBD’s role in treating both motor and non-motor symptoms of PD.

Introduction Acute respiratory distress syndrome (ARDS) is a critical form of acute respiratory failure characterized by diffuse alveolar damage, refractory hypoxemia, and non-cardiogenic pulmonary edema, resulting in high mortality. Dysregulated inflammation, driven by cytokines, is central to ARDS pathogenesis, progression, and prognosis. Objective This review synthesizes current knowledge on the role of cytokines in ARDS and evaluates their potential as therapeutic targets, offering new insights for clinical management. Methods A comprehensive analysis of recent studies was conducted to explore the roles of pro-inflammatory cytokines (e.g., IL-1β, IL-6, IL-8) and anti-inflammatory cytokines (e.g., IL-10, IL-22) in ARDS pathogenesis and to assess current and emerging therapies targeting these cytokines. Results Pro-inflammatory cytokines are crucial in initiating inflammatory responses and lung injury in early ARDS, while anti-inflammatory cytokines help regulate and resolve inflammation. Targeted therapies, such as IL-1 and IL-6 inhibitors, show potential in managing ARDS, particularly in COVID-19, but their clinical efficacy is still debated. Combination therapy strategies may enhance outcomes, but further large-scale, multicenter randomized controlled trials are required to establish their safety and efficacy. Conclusion Understanding cytokine regulation in ARDS could lead to innovative therapeutic approaches. Future research should focus on cytokine roles across ARDS subtypes and stages and develop biomarker-driven, individualized treatments.

Ischemic stroke, which accounts for the majority of stroke cases, triggers a complex series of pathophysiological events, prominently characterized by acute oxidative stress due to excessive production of reactive oxygen species (ROS). Oxidative stress plays a crucial role in driving cell death and inflammation in ischemic stroke, making it a significant target for therapeutic intervention. Nanomedicine presents an innovative approach to directly mitigate oxidative damage. This review consolidates existing knowledge on the role of oxidative stress in ischemic stroke and assesses the potential of various ROS-scavenging nanoparticles (NPs) as therapeutic agents. We explore the properties and mechanisms of metal, metal-oxide, and carbon-based NPs, emphasizing their catalytic activity and biocompatibility in scavenging free radicals and facilitating the delivery of therapeutic agents across the blood–brain barrier. Additionally, we address the challenges such as cytotoxicity, immunogenicity, and biodistribution that need to be overcome to translate these nanotechnologies from bench to bedside. The future of NP-based therapies for ischemic stroke holds promise, with the potential to enhance outcomes through targeted modulation of oxidative stress.

Background NRXN1 -related disorders are uncommonly reported. The clinical features of the disorders are wide and heterogeneous mainly consisting of undistinctive facial dysmorphism, mild to severe intellectual and speech delay, epileptic seizures, and motor dysfunction. Defects in NRXN1 gene have been identified in cases diagnosed as Pitt-Hopkins-like-syndrome 2 (PTHLS2; OMIM#614325). Methods Literature review of NRXN1 -related disorders was conducted and main clinical features of individuals affected by these disorders were analyzed. In addition, clinical features of individuals labelled with PTHSL2 diagnosis were reported. A comparison between international consensus diagnostic criteria for Pitt-Hopkins syndrome (PTHS) and twins presenting with NRXN1 -related disorder and followed by this institution were also presented. Results Our data confirmed that NRXN1 -related disorders mainly manifest with undistinctive dysmorphic features and neurological involvement consisting of more or less severe developmental delay/intellectual disability, autistic spectrum disorder, and epilepsy. Relationship between PTHSL2 and NRXN1 remains to be established. Conclusions Our present analysis denoted a heterogeneous and unspecific clinical framework of the NRXN1 -related disorders mainly affecting the nervous system for which the clinical diagnosis remains inconclusive without the support of genetic analysis. Further contributions are necessary to better clarify the clinical assessment of PTHSL2.

Introduction Complex regional pain syndrome (CRPS) is a chronic pain condition most often triggered by direct injury to an extremity that is characterized by disproportionate pain, sensory abnormalities, and autonomic dysfunction. Early research into intravenous lidocaine therapy for CRPS has demonstrated promise, but clinical evidence remains scarce. We report on 12 patients with chronic CRPS who underwent intravenous lidocaine therapy and discuss our findings in the context of the existing literature. Results Patients ages ranged from 25 to 64 years. Duration of CRPS ranged from 4 to 25 years. The majority of patients (8/12, 67%) reported adequate subjective pain relief with intravenous lidocaine therapy, whereas four patients reported inadequate subjective pain relief with therapy. All patients were being treated with at least one other pharmacotherapy. Three patients experienced minor side effects. Conclusions Our cases, taken with existing evidence, suggest that intravenous lidocaine for the treatment of chronic CRPS is safe and may decrease the pain associated with chronic CRPS. However, this study lacks adequate sample size to make those conclusions confidently. We recommend a randomized placebo-controlled multicenter clinical trial to establish the efficacy and side effect profile of systemic intravenous lidocaine more confidently for the treatment of pain due to chronic CRPS.

Background Osteosarcoma, a highly malignant skeletal tumor, primarily affects children and adolescents. Autophagy plays a crucial role in osteosarcoma pathophysiology. This study utilizes bibliometric analysis to evaluate current research on autophagy in osteosarcoma and forecast future directions. Methods We conducted a comprehensive search of publications in the Web of Science Core Collection database from January 1, 2008, to March 15, 2024. Tools like VOSviewer, CiteSpace, R software, Excel, and Scimago were used for analysis and visualization. Results Publications increased steadily over 17 years, indicating rising interest. Zhang Yuan was the most influential author, with Shanghai Jiao Tong University leading. Cell Death & Disease was the top journal. “HMGB1 Promotes Drug Resistance in Osteosarcoma” was the most cited paper. Co-cited articles focused on drug resistance, therapeutic targets, autophagy in cancer, and genomic impacts on immunotherapy. Keywords highlighted invasion, migration, cell death, and breast cancer as research hotspots. Future studies will likely focus on therapeutic innovations and integrated management strategies. Conclusion This bibliometric analysis offers an overview of current knowledge and emerging trends in autophagy and osteosarcoma, emphasizing key areas like invasion, migration, and cell death. It serves as a valuable resource for researchers developing novel therapies for osteosarcoma.