Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

OBJECTIVE: To comprehensively evaluate the effect of icariin in alleviating reproductive function damage (RFD) in male mice via in vitro and in vivo experiments. METHODS: We isolated Leydig cells from 60 KM male mice in vitro, and examined the toxic effect of icariin on the Leydig cells using Cell Counting Kit-8 (CCK-8). We equally randomized the mice into six groups: normal control, RFD model control (made by intraperitoneal injection of busulfan at 10 mg/kg combined with cyclophosphamide (CP) at 120 mg/kg), positive control, and low-, medium- and high-dose icariin. After modeling, we treated the mice in the positive control group with Wuziyanzong Pills and those in the low-, medium- and high-dose icariin groups by intragastrical administration of icariin at 20, 40 and 80 mg/kg-1, respectively, for 30 successive days. Then we obtained the weight and visceral coefficients of the reproductive organs, calculated the sperm count, observed the pathological changes in the testis tissue by HE staining, measured the serum testosterone (T) level by ELISA, determined the indexes of testicular oxidative stress and nitric oxide (NO) signaling pathway by colorimetric assay, and detected the expression levels of the pro-apoptotic genes Fas and Bax by qRT-PCR. RESULTS: CCK-8 assay confirmed that icariin had no toxic effect on the isolated Leydig cells of the mice, and could effectively reduce busulfan- and CP-induced cytotoxicity and promote the secretion of serum T. Icariin at 80 mg/kg significantly increased the visceral coefficient of the testis and promoted spermatogenesis (P<0.05), but had little effect on the visceral coefficient of the epididymis in the RFD model mice. Testicular histomorphometric observation revealed significantly improved testis structure, intact boundary membrane of seminiferous tubules and increased numbers of various types of spermatogenic cells of the model mice after treated with icariin. Compared with the mice in the model control group, those treated with high-dose icariin showed a significantly reduced content of malondialdehyde (MDA) (by 35.3%, P<0.01), elevated total antioxidant capacity (TAOC) and superoxide dismutase (T-SOD) activity (P<0.05), and decreased NO content and nitric oxide synthase (NOS) activity in the testis tissue (P<0.01). In addition, icariin exhibited an evident inhibitory effect on the expressions of the pro-apoptotic genes Bax and Fas. CONCLUSION Icariin can ameliorate oxidative stress-induced damage to the testicular function and protect spermatogenesis of male mice by elevating TAOC, decreasing NOS activity, inhibiting the NO level in the testis, and suppressing busulfan- and CP-induced apoptosis of testicular cells.
Animals ; Male ; Cyclophosphamide/adverse effects* ; Mice ; Busulfan/adverse effects* ; Flavonoids/pharmacology* ; Leydig Cells/drug effects* ; Oxidative Stress/drug effects* ; Testis/drug effects* ; Apoptosis/drug effects* ; Testosterone/blood*

BACKGROUND: Low serum albumin levels are established predictors of adverse outcomes in various cardiovascular conditions. However, the role of serum albumin in mortality among elderly patients with chronic aortic regurgitation (AR) has not been thoroughly investigated. This study aims to assess the relationship between serum albumin levels and mortality in this specific patient population. METHODS: Our analysis included 873 elderly AR patients from the China Valvular Heart Disease study, with baseline serum albumin measured at enrollment. Mortality outcomes were monitored for two years post-enrollment, employing a Cox proportional hazards model with a two-piecewise Cox proportional hazards framework to investigate the nonlinear relationship between serum albumin levels and all-cause mortality. RESULTS: During the 2-year follow-up period, we observed 63 all-cause deaths. The association between serum albumin levels and all-cause mortality displayed an approximating L-shaped curve, indicating a mortality threshold at 35 g/L. For serum albumin levels below 35 g/L, each 1 g/L decrease was associated with a 25% higher risk of all-cause mortality (HR = 1.25, 95% CI: 1.07-1.45). In contrast, no significant change in mortality risk was observed when serum albumin levels were greater than or equal to 35 g/L. Moreover, when serum albumin is classified as hypoproteinemia (serum albumin < 35 g/L), the higher risks of all-cause death were observed in hypoproteinemic patients (HR = 2.93, 95% CI: 1.50-5.74). More importantly, the association between serum albumin and death was significantly stronger in overweight/obese patients (≥ 24 kg/m² vs. < 24 kg/m², P _interaction = 0.006). CONCLUSIONS In elderly patients with AR, serum albumin levels showed an approximating L-shaped relationship with all-cause death, with thresholds of 35 g/L. Body mass index was significant effect modifiers of the association. These results suggest that serum albumin, as an inexpensive and readily available biochemical marker, may further improve the stratified risk of mortality in older AR patients.

BACKGROUND: It remains unclear whether sleep duration and physical activity (PA) trajectories in middle-aged and older adults are associated with different risks of cardiovascular diseases (CVDs). This study aimed to explore the trajectories of total sleep duration and PA among middle-aged and older Chinese adults and their impact on CVD risk. METHODS: This study was based on the China Health and Retirement Longitudinal Study. 12009 adults aged 45 years and older from five waves were included. CVD events were measured by self-reports of heart disease and stroke. We first used group-based trajectory modeling to identify total sleep duration and PA trajectories from 2011 to 2020, and then employed logistic regression models to analyze their risk for CVD. RESULTS: We identified three sleep duration and PA trajectories. The risk of heart disease increased by 33% (OR = 1.31, 95% CI: 1.12-1.53) for the short sleep duration trajectory (vs. moderate sleep duration trajectory), by 40% (OR = 1.40, 95% CI: 1.06-1.84) for the high decreasing PA trajectory, and by 20% (OR = 1.20, 95% CI: 1.01-1.42) for the low stable PA trajectory (vs. high stable PA trajectory), respectively. Similar results for stroke and CVD as the outcomes were also observed, but the higher risk of stroke in the high decreasing PA trajectory group was not statistically significant. The joint effects of sleep and PA showed lower risks of heart disease and stroke in trajectories with moderate or long sleep duration and high stable PA compared with short sleep duration and a low stable PA trajectory. CONCLUSIONS Short total sleep duration, high decreasing PA, and low stable PA trajectories could increase the risk of CVDs among middle-aged and older adults. Long-term moderate to long total sleep durations and high stable PA trajectories might be optimal for preventing CVDs.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Immune thrombocytopenia (ITP) is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury. ITP has complicated immunopathological mechanisms that need further elucidation. It is well known that the costimulatory molecules OX40 ligand (OX40L) and OX40 play essential roles in the immunological mechanisms of autoimmune diseases. Previously, we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells (PBMCs) of ITP patients. In our present study, OX40L-induced follicular helper T (Tfh) cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PD-1), and cluster of differentiation 40 ligand (CD40L) in vitro. Moreover, aberrant OX40L‒OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo, inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model, which might accelerate the progression of ITP. Additionally, signal transduction through the OX40L‒OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor (TRAF)‒nuclear factor-κB (NF-κB) and Janus kinase (JAK)‒signal transducer and activator of transcription (STAT) signaling pathways. Overall, OX40L‒OX40 signaling is proposed as a potential novel therapeutic target for ITP.
Animals ; OX40 Ligand/physiology* ; Purpura, Thrombocytopenic, Idiopathic/immunology* ; Cell Differentiation ; Mice ; T-Lymphocytes, Helper-Inducer/cytology* ; T Follicular Helper Cells/cytology* ; Signal Transduction ; Receptors, OX40 ; Mice, Inbred C57BL ; Humans ; Female