Residual inflammatory risk （RIR） is a key issue to be urgently addressed in the secondary prevention of atherosclerotic cardiovascular disease （ASCVD）. Targeted intervention of RIR has become a novel target for drug development and clinical management. A series of high-quality randomized controlled trials （RCTs）， including COLCOT， LoDoCo2 and CLEAR SYNERGY， provided high-level evidence and confirmed that low-dose colchicine （0.5 mg/d） significantly reduced the risk of cardiovascular events in ASCVD patients at stable stage or after the acute phase， while its efficacy varied in different clinical scenarios. International authoritative guidelines from the European Society of Cardiology and the American Heart Association/American College of Cardiology include low-dose colchicine in the recommendations for ASCVD secondary prevention. Two domestic guidelines released in 2024， namely the Guideline for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndrome （ 2024 ） and the Guideline for the Diagnosis and Management of Chronic Coronary Syndrome in China ， have also added relevant recommendations. Nevertheless， due to potential racial differences， safety concerns regarding drug-drug interactions， and the relative lack of clinical evidence in China， especially the absence of prospective RCTs using low-dose colchicine for secondary prevention of ASCVD patients， current clinical recommendations still mainly based on international evidence and guidelines， and should not be simply extrapolated.

Objective : To investigate the mechanism of prostaglandin E synthase 3(PTGES3)/heat shock protein 90(HSP90) in the medial prefrontal cortex regulating obesity-related cognitive dysfunction. Methods: This study consisted of clinical trials and animal experiments. In part one, obese patients scheduled for bariatric surgery, and healthy adults matching gender and age were recruited at the same time to reach 10 cases in each group. The cognitive level was assessed with trail making test part A(TMT-A) and victoria stroop tests(VST). Four-dimensional data-independent acquisition(4D-DIA) was used to screen the proteome changes in peripheral blood. In part two, forty SPF healthy male C57BL/6J mice were randomly divided into four groups: normal diet group(ND group), high fat diet induced obesity group(DIO group), DIO supplemented with the control virus group(DIO+Scramble group) and DIO supplemented with the interfering virus group(DIO+shPTGES3 group). The Morris water maze test was conducted to evaluate the cognitive behavior changes of the four groups of mice. The immunofluorescence staining was performed to detect the expression of PTGES3 and HSP90 in the medial prefrontal cortex and the activation of ionized calcium binding adapter molecule 1(IBA1)-labeled microglia. Results: In the case-control study, the cognitive function of obese patients significantly decreased, and the expression of PTGES3 in peripheral blood significantly increased, while the level of PTGES3 was negatively correlated with cognitive function. In animal experiments, compared with ND group, DIO group had significantly prolonged time reaching the target platform, otherwise, the residence time in the target quadrant was shortened in the Morris water maze test. Simultaneously, there were significant increase in the expression of PTGES3 and HSP90, and the activation of IBA1 in the medial prefrontal cortex. Compared with DIO+Scramble group, mice in the DIO+shPTGES3 group spent less time reaching the target platform, and stayed longer in the target quadrant. The expression and co-localization levels of PTGES3 and HSP90 in medial prefrontal cortex significantly decreased. The activation level of microglia cells was also attenuated by PTGES3 interference. Conclusion Obesity-related cognitive dysfunction may be attributed to PTGES3/HSP90 in the medial prefrontal cortex by mediating neural inflammation.

Objective To map the super-enhancers remodeling of intestinal gastric cancer and reveal the tumor biological functions of the super-enhancers and the downstream target genes that may be activated.Methods A total of 31 normal gastric mucosal tissues,23 intestinal gastric cancer tissues and 9 intestinal gastric cancer organoids were collected from the Department of Gastroenterology of Army Medical Center of PLA from January to December 2022.Chromatin targeting histone H3K27ac modified chromatin targeting cleavage under targets and tagmentation(CUT&Tag)sequencing was conducted on above tissues.The remodeling profiles of super-enhancers in intestinal gastric cancer were analyzed and the key target genes were identified based on bioinformation tools.CRISPRi technology was used to intervene with the super-enhancers,the expression of target genes was detected with Western blotting,and the proliferation,migration and invasion abilities were detected by CCK-8 assay and Transwell chambers in the control group and the intervention group.Results There was a significant difference in the signal of super-enhancers between intestinal gastric cancer tissues and normal gastric mucosal tissues(P<0.05),and the active super-enhancers in cancer tissues may be involved in biological processes such as negative regulation of the immune system and cell adhesion.The expression of up-regulated cell migration-inducing protein(CEMIP)in tumor cells was regulated by the super-enhancers,and intervening the super-enhancers down-regulated the expression of CEMIP(P<0.05),and inhibited the cell proliferation,invasion and migration abilities of tumor cells(P<0.05).Conclusion Super-enhancer remodeling is observed in intestinal gastric cancer,and they can up-regulate the expression of CEMIP gene and promote the growth,migration and invasion of cancer cells.

Objective To identify the enhancer profile marked by histone H3K27ac modification in high-grade intraepithelial neoplasia(HGIN)in order to reveal the novel regulatory mechanism of HGIN pathogensis.Methods Gastric tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA between June 2022 and June 2023,including 14 normal gastric tissues(Nor group),31 HGIN tissues(HGIN group)and 17 gastric cancer tissues(GC group).Cleavage under targets and tagmentation(CUT&Tag)technique was employed to capture enhancer regions modified by histone H3K27ac.Multi-omics analysis was performed to identify HGIN-specific active enhancers and their potentially regulated genes.Immunohistochemical profiling was performed to assess differential expression of the gene of interest across clinically stratified specimens,combined with CRISPR-dCas9-mediated ablation of active enhancers to monitor the gene of interest transcriptional dynamics and validate enhancer-mediated regulatory mechanisms.Results Epigenomic sequencing obtained the data with excellent quality,and indicated that obvious remodeling was observed in H3K27ac enhancers in HGIN and GC groups(P<0.05),though no significant difference in the genome-wide distribution of H3K27ac modification among the 3 groups.Combining transcriptome data revealed that enhancer remodeling may up-regulate the expression of the proliferation-related target gene,CD24,in the HGIN tissue;while,inhibiting enhancer activity can notably reduce CD24 expression level(P<0.05).Immunohistochemical assay displayed a positive correlation between the expression levels of CD24 and Ki-67(P<0.001).Conclusion The remodeling of H3K27ac enhancer represents a significant epigenetic feature of the transformation from normal condition to HGIN.Remodeling of H3K27ac enhancer up-regulates CD24,which may facilitate the abnormal proliferation of gastric epithelial cells.

Objective To analyze clinical characteristics of mesenchymal-subtype gastric cancer(Mes-GC)by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.Methods Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023.Transcriptome and genome sequencing were applied for these tissue samples,including 19 cases of diffuse-type gastric cancer,22 cases of intestinal-type gastric cancer,and 23 cases of mixed-type gastric cancer patients.Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer(non-Mes-GC)by integrating data resources including The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),and National Genomics Data Center(NGDC).Results Compared to non-Mes-GC patients,Mes-GC ones were characterized by later clinical stages,deeper tumor infiltration,and higher rates of lymph node metastasis.Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time,poor prognosis as well as increased risk of cancer recurrence(P<0.05).Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness,metastasis(P<0.05),and epithelial-mesenchymal transition(EMT).And in the tumor microenvironment,there were significant more myeloid cells,smooth muscle cells,endothelial cells and fibroblasts,with the most pronounced elevation in the proportion of fibroblasts(P<0.05).Moreover,the patients with larger proportion of fibroblasts were associated with poorer prognosis.Conclusion Mes-GC tumor cells exhibit higher stemness and EMT characteristics,and stromal cells such as myeloid cells,endothelial cells,and fibroblasts are enriched in the tumor microenvironment.These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

Objective:To investigate the effect of pre-stroke metformin (MET) use on early neurological improvement (ENI) and outcome after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with type 2 diabetes (T2DM).Methods:AIS patients with T2DM underwent IVT in the Department of Neurology, Yuncheng Central Hospital from January 2019 to February 2025 were included retrospectively. According to whether MET was used before onset, they were divided into MET group and non-MET group. Early neurological improvement (ENI) was defined as a decrease in the National Institutes of Health Stroke Scale (NIHSS) score ≥4 at 24 hours after IVT compared to admission, or the NIHSS score was 0-1. At 90 days after onset, the modified Rankin Scale was used for outcome assessment, and ≤2 was good outcome and >2 was poor outcome. Multivariate logistic regression analysis was used to determine the independent influencing factors of ENI and outcome. Results:A total of 115 AIS patients with T2DM were included in the study, with an age of 65.42±12.22 years. There were 83 males (72.2%). Fifty-four patients (47.0%) used MET, and 61 (53.0%) used other hypoglycemic drugs; 43 (37.4%) developed ENI, and 33 (28.7%) had poor outcome at 90 days. There were no significant difference in all baseline data between the MET group and the non-MET group, but the proportions of patients with ENI and good prognosis at 90 days in the MET group were significantly higher than those in the non-MET group (all P<0.05). The proportions of hypertensive patients and baseline NIHSS scores in the ENI group were significantly lower than those in the non-ENI group, while the proportions of patients using MET, antihypertensive drugs, statins, and patients with good outcome was significantly higher than that in the non-ENI group (all P<0.05). The body weight, high-density lipoprotein cholesterol, as well as the proportions of patients using antiplatelet drugs, MET, and patients with ENI in the good outcome group were significantly higher than those in the poor outcome group, while systolic blood pressure, fasting blood glucose, triglycerides, and the proportions of patients with hemorrhagic transformation, and symptomatic intracranial hemorrhage were significantly lower than those in the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that using statins (odds ratio [ OR] 5.291, 95% confidence interval [ CI] 1.599-17.514; P=0.006) and MET ( OR 3.018, 95% CI 1.125-8.092; P=0.006) were the independent influencing factors of ENI; using MET ( OR 0.014, 95% CI 0.001-0.246; P=0.004) and anterior circulation stroke ( OR 0.005, 95% CI 0.000-0.745; P=0.038) were significantly independently associated with good outcome, while high baseline NIHSS score ( OR 2.092, 95% CI 1.198-3.655; P=0.009) and serum homocysteine ( OR 1.202, 95% CI 1.024-1.411; P=0.024) were significantly independently associated with the poor outcome. Conclusion:The use of MET before stroke onset can help improve ENI and clinical outcome in AIS patients with T2DM after IVT.

OBJECTIVE To investigate the role of Bai Ling Long Zao An Shen formula(BLLZ)in sleep improvement in an environmental stress-induced insomnia rat model and explore its underlying mechanisms.METHODS(1)Component analysis:the chemical constituents of the BLLZ extract were analyzed using ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS).(2)Eval-uation of the sedative and hypnotic effect:① Mice:50 ICR mice were randomly divided into normal control group,BLLZ-L group(5,10 and 20 g·kg-1)and diazepam group(DZP,3 mg·kg-1).After five days of intragastric administration,pentobarbital sodium-induced righting reflex and locomotor activity tests were performed.② Rats:8 SD rats were implanted with electrodes and allowed to recover for seven days before baseline EEG data was collected over 24 h.A crossover design(7 d washout period)was employed,with rats randomly assigned to the DZP(3 mg·kg-1)and BLLZ(20 g·kg-1)group.After five days of treatment,24 h EEG recordings were obtained.(3)Insomnia model and interventions:①8 SD rats were allowed to recover for seven days post-surgery,followed by 6 h(14:00-20:00)baseline EEG recording.A 3×3 crossover design was used to assign rats to model(environmental stress-induced insomnia),model+DZP,or model+BLLZ groups.After five days of treatment,insomnia was induced by frequent cage changes(14:00,16:00 and 18:00),and EEG changes were monitored.(4)Mechanistic study:32 SD rats were randomly divided into the normal control group,model group,and model+DZP group.After five days of treatment,hypothalamic tissues were collected for biochemi-cal analysis.γ-aminobutyric acid(GABA),glutamate(Glu),and dopamine(DA)levels were measured using biochemical kits while γ aminobutyric acid receptor subunit alpha-1(GABAA1),core clock proteins period circadian regulator 2(PER2)and circadian locomotor output cycles(CLOCK)protein expressions were assessed by Western blotting.RESULTS(1)Compared with the normal control group,the sleep latency of BLLZ 10 and 20 g·kg-1 and DZP groups was significantly shortened,and the locomotor activity of BLLZ 20 g·kg-1 and DZP groups was significantly reduced;BLLZ 20 g·kg-1 signifi-cantly increased the total sleep time,slow-wave sleep time,and average duration of sleep in normal rats,and significantly reduced the wakefulness time.(2)The total sleep time and slow-wave sleep time of the model group significantly decreased and the wakefulness time significantly increased compared with baseline.(3)Compared with the model group,the total sleep time and slow-wave sleep time of the model+BLLZ group and the model+DZP group were significantly increased,and the wakefulness time significantly shortened.(4)Compared with the normal control group,the Glu/GABA ratio,DA content and CLOCK protein expression were significantly increased and GABAA1 and PER2 protein expres-sion were significantly decreased in the model group;compared with the model group,the Glu/GABA ratio,DA content and CLOCK protein expression were significantly decreased,and the expression of GABAA1 and PER2 were significantly increased in the model+BLLLZ group and the model+DZP group.CONCLUSION BLLZ has sedative and hypnotic effects.It can prolong the total slow-wave sleep time by increasing the average duration of slow-wave sleep episodes,thereby increasing the total sleep time and improving environmental stress-induced insomnia.The mechanism may be related to the downregulation of the Glu/GABA ratio and DA levels as well as the enhancement of GABAA1 expressions and the regulation of hypothalamic core clock protein expressions.

Objective To build a hospital data service portal system based on central authentication service(CAS)to solve the problems of dispersed user identity data and low management efficiency caused by independent operation of multiple systems.Methods The CAS-based hospital data service portal system was designed with B/S architecture and developed with Spring MVC framework,which implemented unified authentication with CAS technology and achieved standardized access protocols for integrated access,centralized management and service consolidation across various application systems.There were five functional modules involved in the system for homepage,workflow management,system administration,log management and message management.Results The system significantly enhanced user accessibility and data extraction efficiency,effectively reduced the complexity of system integration and operational maintenance burdens and ensured user privacy and data security.Conclusion The portal system provides users with an easy-to-use,secure and reliable data service portal,laying the foundation for building an efficient,intelligent and safe hospital data service system.