Objective To explore the association between long working hours, anxiety symptoms, and insomnia symptoms among footwear industry workers, and to examine the mediating effect of anxiety symptoms between long working hours and insomnia symptoms. Methods A total of 710 workers from 15 footwear manufacturing enterprises in Guangdong Province were selected as study subjects using a stratified random sampling method. Long working hours, anxiety symptoms, and insomnia symptoms among the workers were assessed using the National Key Population Occupational Health Literacy Monitoring Questionnaire, the Chinese version of the Generalized Anxiety Disorder Self-Rating Scale, and the Self-Rating Sleep Questionnaire. Binary logistic regression was applied to analyze the associations of long working hours and anxiety symptoms with insomnia symptoms, and a mediation effect model was used to examine the mediating role of anxiety symptoms. Results The workers with long working hours accounted for 69.6% of participants. The detection rates of anxiety symptoms and insomnia symptoms were 17.0% and 20.7% in these workers, respectively. Binary logistic regression analysis showed that both long working hours and anxiety symptoms were influencing factors for insomnia symptoms (both P<0.01). Mediation analysis indicated that long working hours had a direct effect on insomnia symptoms, accounting for 67.9% of the total effect. Anxietysymptoms played a partial mediating role between long working hours and insomnia symptoms, with an effect value of 0.18 (95% confidence interval 0.07-0.30, P<0.01), accounting for 32.1% of the total effect. Conclusion Both long working hours and anxiety symptoms are influencing factors for insomnia symptoms among the footwear industry workers, and anxiety symptoms partially mediate the impact of long working hours on insomnia symptoms.

OBJECTIVE To analyze the comprehensive intervention measures to raise the etiological submission rate for hospitalized patients before antimicrobial treatment and evaluate the effect.METHODS The hospitalized pa-tients who were treated with therapeutic antibiotics in the Affiliated Hospital of Inner Mongolia Medical University from Jan.2023 to Jun.2023 were assigned as the exploratory analysis phase,the hospitalized patients who were treated with therapeutic antibiotics from Jul.2023 to Dec.2023 were assigned as the first post-intervention phase,and the hospitalized patients who were treated with therapeutic antibiotics from Jan.2024 to Mar.2024 were as-signed as the second post-intervention phase.The related indexes for etiological submission rate before the antimi-crobial treatment were compared before and after the intervention.RESULTS After the comprehensive interven-tion,the etiological submission rate of the entire hospital before the antimicrobial treatment was increased from 28.30％to 42.22％in the first post-intervention phase and 55.86％in the second post-intervention phase.The etio-logical submission rate with respect to diagnosis of hospital-associated infection was increased from 68.34％before the intervention to 85.85％in the first post-intervention phase and 94.58％in the second post-intervention phase.The incidence of hospital-associated infection showed a slight downward trend,dropping from 1.51％to 1.27％in the first post-intervention phase and 1.11％in the second post-intervention phase.The proportion of submission of sterile samples showed a slight upward trend,which was 26.13％before the intervention,29.57％in the first post-intervention phase,28.96％in the second post-intervention phase.There were significant differences in the a-bove indexes(P＜0.05).The etiological submission rate before the combined use of key drugs was increased from 84.71％to 85.95％in the first post-intervention phase and 88.33％in the second post-intervention phase,and there was no significant difference.CONCLUSIONS The etiological submission rate of the hospitalized patients be-fore the antimicrobial treatment is remarkably raised by taking the comprehensive intervention measures,but the etiological submission rate before the combined use of key drugs does not meet the standard,the proportion of submission of the sterile samples is not remarkably raised.It is necessary to continuously complete the intervention measures in the next phase.

Objective:To investigate the effects and underlying mechanisms of the hypoxia-inducible factor-1α (HIF-1α) agonist Roxadustat in alleviating pulmonary ischemia-reperfusion injury (IRI) in mice.Method:This study consisted of both in vivo and in vitro experiments. Thirty-six male C57/BL6 mice (6~8 weeks old) were used. In the animal experiments, 20 mice underwent left pulmonary artery ligation to establish the IRI model and were divided into reperfusion groups of 0, 1, 2, or 4 hours (IR-0/1/2/4 h, n=4 each), with a sham group ( n=4) as control. Temporal and spatial changes in pulmonary HIF-1α expression were analyzed. Another 16 mice were randomized into four groups: sham ( n=4), I/R+vehicle (DMSO, n=4), and I/R+Roxadustat treatment at 25 mg/kg or 50 mg/kg (I/R+ROX-LD, I/R+ROX-HD, n=4 each). Roxadustat or DMSO was administered intraperitoneally once daily for 5 days before surgery. Lung injury, inflammation, and endothelial apoptosis were subsequently assessed. In the cell experiments, human umbilical vein endothelial cell (HUVEC) was subjected to hypoxia-reoxygenation (H/R) to determine the time course of HIF-1α expression. Cells pretreated with Roxadustat (25 μmol) were then exposed to H/R, and HIF-1α expression and apoptosis were analyzed. To verify the role of HIF-1α, siRNA knockdown of HIF-1α mRNA was performed before Roxadustat pretreatment and H/R exposure. Result:In vivo, pulmonary HIF-1α mRNA expression increased progressively after reperfusion, while protein expression peaked early and subsequently declined ( P<0.05). Immunofluorescence staining revealed HIF-1α predominantly localized to pulmonary endothelial cells following I/R. Compared with the I/R+DMSO group, Roxadustat (both doses) upregulated HIF-1α expression in lung tissue. In vitro, HIF-1α mRNA expression increased continuously after H/R, while protein levels first rose and then decreased ( P<0.05). Roxadustat pretreatment upregulated Bcl-2 and downregulated Bax and cleaved caspase-3 compared with the H/R group ( P<0.05). HIF-1α knockdown reversed these effects, resulting in decreased Bcl-2 and increased Bax and cleaved caspase-3 expression relative to the Roxadustat-treated group. Conclusion:The HIF-1α agonist Roxadustat inhibits vascular endothelial apoptosis, alleviates endothelial injury, reduces inflammatory cell infiltration in lung tissue, and lowers inflammatory responses in mice with pulmonary ischemia-reperfusion injury.

The "Chinese guidelines for diagnosis and treatment of neuromyelitis optica spectrum disorders (2025 edition)" is based on evidence-based medicine and closely integrates the latest research progress at home and abroad, comprehensively updating the 2021 edition of the guidelines. Firstly, in terms of clinical manifestations and diagnostic criteria, it is pointed out that antibody detection based on live cells has higher sensitivity, and magnetic resonance imaging as well as optical coherence tomography can provide more meaningful evaluation parameters. Secondly, the content regarding clinical manifestations, differential diagnosis, and warning signs is more abundant and intuitive. Thirdly, sequential treatments are clearly classified into therapies within the indications and off-label empirical therapies. Meanwhile, the innovative therapeutic drug, ravulizumab, a long-acting monoclonal antibody targeting complement C5, is introduced. A detailed elaboration is made on the whole-process management of drug treatment, covering the timing of initiating treatment, planning of the treatment sequence, switching strategies of immunotherapies, key points of treatment monitoring, and treatment regimens for antibody-negative neuromyelitis optica spectrum disorders. In addition, for the group of women of childbearing age, key issues such as the timing of family planning and the selection of drugs during pregnancy are discussed, providing more scientific, standardized, and practically relevant guidance for clinical diagnosis and treatment.

Objective To explore whether virtual reality(VR)combined with computerized cogni-tive training intervention can improve the cognitive function in elderly stroke patients.Methods A total of 202 stroke patients admitted to our department from January 2022 to January 2024 were recruited and randomly divided into control group(101 cases,traditional cognitive training intervention)and study group(101 cases,VR combined with computerized cognitive training in-tervention).Before and after 3 months of intervention,Montreal Cognitive Assessment Scale(MoCA),Mini-Mental State Examination(MMSE),National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FMA),Activities of Daily Living Scale(ADL)were applied,serum levels of dopamine,neuropeptide Y(NPY),5-hydroxytryptamine(5-HT)and norepineph-rine(NE)were detected,and P300 wave of event-related potential was measured.The results were compared before and after intervention,and between the two groups.Results After intervention,the scores of MoCA,MMSE and FMA,the levels of NPY,5-HT,NE,dopamine,and the ampli-tude of P300 wave were obviously higher in both groups when compared with those before inter-vention(P＜0.05).The study group obtained notably higher MoCA score(27.64±0.62 vs 26.83±0.65),MMSE score(27.67±0.61 vs 26.83±0.62),NPY,5-HT,NE,dopamine,FMA score and amplitude of P300 wave after intervention than the control group(P＜0.01).The NIHSS score,ADL score and latency in the two groups after intervention were significantly lower than those before intervention(P＜0.05),and the above indicators in the study group were significantly low-er than the control group(P＜0.01).Conclusion VR combined with computerized cognitive training intervention can effectively improve the cognitive function,neurological function,motor function and daily life function,and enhance the neurotransmitter levels in elderly stroke patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

The accurate and timely detection of biochemical coagulation indicators is pivotal in pulmonary and critical care medicine. Despite their reliability, traditional laboratories often lag in terms of rapid diagnosis. Point-of-care testing (POCT) has emerged as a promising alternative, which is awaiting rigorous validation. We assessed 226 samples from patients at the First Affiliated Hospital of Guangzhou Medical University using a Beckman Coulter AU5821 and a PUSHKANG POCT Biochemistry Analyzer MS100. Furthermore, 350 samples were evaluated with a Stago coagulation analyzer STAR MAX and a PUSHKANG POCT Coagulation Analyzer MC100. Metrics included thirteen biochemical indexes, such as albumin, and five coagulation indices, such as prothrombin time. Comparisons were drawn against the PUSHKANG POCT analyzer. Bland-Altman plots (MS100: 0.8206‒0.9995; MC100: 0.8318‒0.9911) evinced significant consistency between methodologies. Spearman correlation pinpointed a potent linear association between conventional devices and the PUSHKANG POCT analyzer, further underscored by a robust correlation coefficient (MS100: 0.713‒0.949; MC100: 0.593‒0.950). The PUSHKANG POCT was validated as a dependable tool for serum and whole blood biochemical and coagulation diagnostics. This emphasizes its prospective clinical efficacy, offering clinicians a swift diagnostic tool and heralding a new era of enhanced patient care outcomes.
Humans ; Point-of-Care Testing ; Critical Care ; Blood Coagulation Tests/methods* ; Male ; Blood Coagulation ; Female ; Middle Aged ; Reproducibility of Results ; Prothrombin Time ; Aged ; Adult ; Point-of-Care Systems

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People