BACKGROUND: Serum osmolality is a prognostic indicator in critically ill patients. This study aimed to evaluate the association between high osmolality and 28-day mortality in patients with cardiac arrest (CA) admitted to the intensive care unit (ICU). METHODS: Baseline data of adult patients with CA who were admitted to the ICU from 2008 to 2019 were collected from the Medical Information Mart for Intensive Care (MIMIC)-IV. Patients were divided into survivor and non-survivor groups according to the 28-day prognosis. Serum concentrations of sodium, potassium, glucose, and urea nitrogen on the first day of ICU admission were used to determine serum osmolarity. The primary endpoint of this study was 28-day all-cause mortality. Propensity score matching (PSM) analysis was performed to reduce bias between the survivor and non-survivor groups. RESULTS: Among the 798 included CA patients, the high osmolarity on the first day of ICU admission remained significantly associated with increased 28-day mortality (62.0% vs. 35.5%, P<0.001) and reduced cumulative survival (log-rank P<0.05) after PSM. Cox regression identified the high osmolarity on the first day of ICU admission as an independent predictor. High serum osmolarity on the first day of ICU admission effectively predicted 1-, 3-, 7-, and 28-day all-cause mortality, with the strongest predictive performance for 1-day mortality both before and after PSM (all P<0.05). CONCLUSION: In this study, elevated serum osmolarity on the first day of ICU admission was independently associated with increased 28-day mortality in CA patients and could serve as a prognostic marker.

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Coagulation factor XIa (FXIa) plays a crucial role in thrombus formation; therefore, the development of potent and safe FXIa inhibitors is of great significance. In this study, compound F22, previously discovered by our group, was selected as the lead compound. Based on the principles of bioisosterism and fragment-based drug design, four series comprising 14 novel Asundexian derivatives not previously reported in the literature were designed and synthesized. The structures of the target compounds were confirmed by 1H NMR and HRMS, and their inhibitory activities against FXIa were evaluated using chromogenic substrate assay. Results showed that compound FD-1 exhibited the most potent activity, with an IC50 value of 2.8 nmol/L, which was superior to that of the lead compound F22 (IC50 = 4.5 nmol/L) and the reference drug Asundexian (IC50 = 5.0 nmol/L). Furthermore, in the activated partial thromboplastin time (aPTT) assay, compound FD-1 demonstrated excellent anticoagulant activity, outperforming Asundexian, showing no significant effect on prothrombin time (PT). These findings provide valuable insights for further structural optimization and rational design of small-molecule FXIa inhibitors.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

Prolonged standing work can lead to various lower limb health issues. Footwear, as a convenient and noninvasive intervention, plays a key role in foot protection. The purpose of this review was to evaluate the impact of footwear characteristics on foot comfort among workers engaged in prolonged standing occupations. A systematic search of PubMed, Web of Science, Scopus, and the Cochrane Library was conducted until March 2025 for experimental and observational studies; the review is registered in International Prospective Register of Systematic Reviews (CRD420251003253).Given the diversity of study designs, participant characteristics, and outcome measures, results were synthesized narratively, organizing findings by footwear design factors. The synthesis indicated that soft soles reduce foot impact and fatigue but offer limited support, whereas hard soles enhance stability but may cause localized pressure and discomfort. Sole hardness should balance cushioning and support based on activity: hard soles for standing and soft soles for walking. Insole hardness must be carefully considered as semirigid arch supports can cause discomfort. Most insoles improve pressure distribution by adjusting arch loading, and some enhance intrinsic foot muscles by promoting toe engagement, reducing leg swelling. Custom orthotic insoles outperform standard ones in comfort and balance. Future research should promote interdisciplinary collaboration with footwear designers to explore key design parameters and establish a scientific framework for protective footwear.

ObjectiveTo explore psychological experiences and care needs of elderly patients with chronic obstructive pulmonary disease (COPD) following dysphagia. MethodsFrom April to June, 2024, 13 elderly patients with COPD and dysphagia received treatment in Yixing No. 2 People's Hospital (Yixing Occupational Disease Institute) and Northern Jiangsu People's Hospital were interviewed. Nvivo 11.0 and content analysis were employed to analyze and summarize themes. ResultsTwo main themes were identified. The psychological experiences included fear of eating due to swallowing and choking, swallowing anxiety in social situations, concerns about malnutrition, and emotional loss related to family. The care needs included improvement in swallowing function, adjustment of food texture, assistance with disease adaptation and effective access to health education information. ConclusionHealthcare professionals should thoroughly understand the psychological and needs of elderly patients with COPD-related dysphagia, and comprehensive nursing strategies should be developed and implemented to improve swallowing function and overall quality of life.

The present study employed UPLC-MS/MS to analyze and identify compounds in the raw powder of Tongluo Shenggu capsules. An HPLC method for the determination of vitexin content was established. The analysis of this drug was performed on a 30 ℃ thermostatic Acquity UPLC® BEH C18 (2.1 mm×100 mm,1.7 μm) column, with the mobile phase comprising 0.2% formic acid-methanol flowing at 0.3 mL /min in a gradient elution manner. Mass spectrometry was detected by ESI sources in both positive and negative ion modes for qualitative identification of chemical constituents. 12 flavonoid and 3 stilbenes compounds in the raw powder of Tongluo Shenggu capsules were successfully identified. Additionally, an HPLC method for the determination of vitexin content was established using a XBridge C18 column (4.6 mm × 250 mm, 5 µm) with a mobile phase of 0.05% glacial acetic acid in methanol for gradient elution, at a column temperature of 30 °C, a flow rate of 1.0 mL/min, and an injection volume of 20 μL. The method demonstrated good linearity in the concentration range of 10 µg/mL to 40 µg/mL (R=1.000) with an average recovery rate of 96.7%. The establishment of these methods provides a scientific basis for the quality control and development of the raw powder of Tongluo Shenggu capsules.

Objective To investigate the predictive value of neuregulin 4(Nrg4)combined withγ-aminobutyric acid(GABA)in cognitive dysfunction among patients with severe obstructive sleep apnea-hypopnea syndrome(OSAHS).Methods A total of 169 patients with severe OSAHS were se-lected as study subjects and divided into normal cognitive function group(n=89)and cognitive dys-function group(n=80)based on cognitive function assessment results.General information of the pa-tients was collected,and the levels of Nrg4 and GABA were detected by enzyme-linked immunosor-bent assay(ELISA).Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of Nrg4 and GABA for cognitive dysfunction in OSAHS patients.Results The proportions of patients with a history of hypertension and diabetes,as well as the levels of diastolic blood pressure,total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were significantly higher in the cognitive dysfunction group than those in the normal cognitive function group(P＜0.05).The levels of Nrg4 and GABA were significantly lower in the cognitive dysfunction group than in the normal cognitive function group(P＜0.05).The Montreal Cognitive Assessment(MoCA)score in the cognitive dys-function group was significantly lower than that in the normal cognitive function group[(12.36±2.35)versus(28.25±1.02),P＜0.05].Multivariate Logistic regression analysis revealed that a history of hypertension and diabetes,diastolic blood pressure,TC,TG,HDL-C,and LDL-C were risk factors for cognitive dysfunction in patients with severe OSAHS(P＜0.05),while Nrg4,GABA,and MoCA scores were protective factors(P＜0.05).ROC curve analysis showed that combined de-tection of Nrg4 and GABA had a higher predictive value for cognitive dysfunction in patients with se-vere OSAHS compared with either marker alone(P＜0.05).Conclusion A history of hyperten-sion and diabetes,diastolic blood pressure,TC,TG,HDL-C,LDL-C,Nrg4,GABA,and MoCA scores are all factors influencing cognitive dysfunction in patients with severe OSAHS.Combined de-tection of Nrg4 and GABA can effectively predict cognitive dysfunction in these patients.

Elucidate the influence of RFRP-3 on follicular development and steroid hormone synthe-sis in mice.Forty 6-week-old female KM mice were randomly allocated into four groups,namely the 0(control),100,500 and 2 000 ng/d treatment groups.Each group received daily intraperitoneal injections of RFRP-3 for a duration of 7 days.The ovarian coefficients were calculated and recorded by measuring the wet weight of the ovaries.The effects of RFRP-3 at different concentrations on follicular maturation in mice were investigated through HE staining.Western blot analysis was em-ployed to assess the expression of apoptosis-related proteins,steroidogenic enzymes,and oocyte se-cretion factors within the mouse ovaries.The concentrations of progesterone(P4)and estradiol(E2)in the serum of the mice were determined using radioimmunoassay techniques.The results re-vealed no significant differences in body weight between the experimental groups and the control.However,the ovarian coefficients in the 500 and 2 000 ng/d treatment groups were significantly re-duced when compared to the control(P＜0.01).A marked decrease in the numbers of secondary and antral follicles was observed in the 500 ng/d and 2 000 ng/d groups(P＜0.01),concomitant with a substantial increase in atretic follicles(P＜0.01).A significant decline in follicle count was also noted in these groups(P＜0.01).Compared to the control,the protein expression of Bax and Caspase3 was substantially upregulated in the 500 and 2 000 ng/d treatment groups(P＜0.05),while the expression of Bcl-2 protein was significantly downregulated(P＜0.01).Similarly,the protein expression of 3βHSD,StAR,CYP11a1,and CYP17a1 was significantly decreased at the 500 and 2 000 ng/d groups(P＜0.01).E2 concentrations were moderately reduced in the 500 ng/d group(P＜0.05)and significantly decreased in the 2000 ng/d group(P＜0.01),whereas P4 levels remained unchanged across all experimental groups.Notably,the expression of BMP15 and GDF9 at both the gene and protein levels was markedly attenuated in the 500 and 2 000 ng/d treatment groups compared to the control(P＜0.05).In conclusion,RFRP-3 appears to inhibit follicular de-velopment and steroid hormone secretion in mice by modulating the expression of apoptotic fac-tors,oocyte secretion factors,and steroidogenic enzymes within the ovaries.This study provides a theoretical foundation for understanding the regulatory mechanisms of RFRP-3 on mammalian follicular development and steroid hormone synthesis.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.