Currently,there are practical and technical difficulties in the construction of clinical ques-tions in the development of clinical practice guidelines.Clinicians or guideline developers seldom construct clin-ical questions based the actual case scenario,leading to some information loss between structured and actual clinical connotation.To overcome this challenge,we proposed a case-guided questions construction approach,and carried out case research and verification in the formulation of the guideline.We found that this method could more efficiently and scientifically assist the formulation of clinical questions,and provide reference for clinicians or guideline developers.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Objective:To explore the effect of ezetimibe combined with atorvastatin on the efficacy,blood lipids,ca-rotid ultrasound indicators in patients with coronary heart disease(CHD)and its safety.Methods:This randomized controlled study enrolled 98 CHD patients admitted to 945th Hospital of the PLA Joint Logistic Support Force be-tween June 2021 and June 2023.Patients were divided into intervention group and control group with 49 cases in each group.Patients in the control group was treated with atorvastatin-bascd routine medication comparing to those in intervention group receiving additional ezetimibe,both groups were treated for 90 d.Clinical efficacy,blood lipids,carotid ultrasound indicators,endothelial function indicators,and incidence of adverse reactions were compared between two groups.Results:Compared with patients in the control group,those in the intervention group had significant higher total effective rate(91.83％vs.73.47％,P=0.016).Compared with patients in the control group after treatment,those in intervention group had significant lower levels of low density lipoprotein cho-lesterol(LDL-C)[(2.74±0.61)mmol/L vs.(3.42±0.66)mmol/L],total cholesterol(TC)[(3.80±0.89)mmol/L vs.(4.69±1.02)mmol/L],triglyceride(TG)[(1.79±0.53)mmol/L vs.(2.35±0.62)mmol/L],re-sistance index(RI)[(52.02±6.32)％vs.(57.95±6.02)％],carotid intima-media thickness(IMT)[(0.91±0.17)mm vs.(1.08±0.24)mm],von Willebrand factor(vWF)[(19.03±3.76)mg/L vs.(23.41±4.42)mg/L],angiotensin Ⅱ(Ang Ⅱ)[(45.83±5.87)ng/L vs.(52.87±6.01)ng/L](P＜0.001 all);and significant high-er high density lipoprotein cholesterol(HDL-C)[(1.63±0.32)mmol/L vs.(1.35±0.27)mmol/L],peak systol-ic velocity(PSV)[(47.93±5.26)cm/s vs.(41.32±4.98)cm/s],end-diastolic velocity(EDV)[(36.14±5.10)cm/s vs.(30.73±4.48)cm/s],pulse index(PI)[(85.98±9.03)％vs.(78.42±8.82)％],vascular endothelial growth factor receptor 1(VEGFR1)[(289.14±32.98)ng/L vs.(258.34±29.32)ng/L](P＜0.001 all).There was no significant difference in the incidence of adverse reactions between the two groups(P=0.538).Conclusion:Ezetimibe combined with atorvastatin possesses significant therapeutic effect on CHD patients,which could signifi-cantly reduce blood lipids,improve the carotid blood flow velocity and vascular endothelial function with good safety.

AIM:To investigate the preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P＜0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.

Objective:To explore the changes in the whole transcriptome gene expression profile affected by EPB41L4A-AS,and to reveal its potential mechanisms that influence the progression of AD.Methods:U251 cells with stable low expression of EPB41L4A-AS1 were constructed using shRNA technology.Transcriptome sequencing was performed to screen for transcripts regulated by EPB41L4A-AS1.KEGG pathway and GO analysis were used to explore the related signaling pathways and biological processes regulated by EPB41L4A-AS1.Immunofluorescence assay was used to investigate the effects of EPB41L4A-AS1 on the activity of glial cells with antibodies against GFAP.Results:Knocking down the expression of EPB41L4A-AS1 in U251 cells significantly influenced the levels of multiple transcripts,with 626 upregulated and 949 downregulated.Further analysis revealed that the downregulated transcripts are related to AD,activation and proliferation of glial cells,and formation of amyloid fibers,and close to multiple signaling pathways that are involved in the glial cells-mediated Aβ clearance.Cellular experiments have shown that EPB41L4A-AS1 regulated the synapses length and activity of glial cells.Conclusions:EPB41L4A-AS1 may influence the glial cells-mediated Aβ clearance through multiple signaling pathways.

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.