ObjectiveTo analyze the clinicopathological features of patients with comorbidities of chronic hepatitis B （CHB） and steatotic liver disease （SLD）， to investigate the impact of hyperglycemia on the risk of liver fibrosis and end-stage liver diseases （ESLD）， and to provide a basis for the clinical management of such population. MethodsA total of 668 adult patients with CHB-SLD confirmed by liver biopsy in The Fifth Medical Center of Chinese PLA General Hospital from January 2011 to December 2019 were enrolled， and a retrospective cohort was established with the time of liver biopsy as the baseline and the onset of ESLD as the endpoint. All patients were followed up to March 31， 2024. Propensity score matching （PSM） was performed at a ratio of 1∶4 to balance baseline features between groups， resulting in 82 patients in the hyperglycemia group and 281 in the non-hyperglycemia group. The two groups were compared in terms of metabolic profiles， laboratory markers， and histopathological features. The Mann-Whitney U test was used for comparison of non-normally distributed quantitative data between two groups. The chi-square test or Fisher exact test was used for comparison of categorical data between two groups. A multivariate Logistic regression analysis was used to investigate the influencing factors for advanced fibrosis （AF）， and the Kaplan-Meier survival analysis and the Cox proportional-hazards regression model were used to determine the influencing factors for the development of ESLD. ResultsCompared with the non-hyperglycemia group， the hyperglycemia group had a significantly higher number of factors for metabolic disorders， a significantly higher degree of hepatic steatosis， and a significantly higher detection rate of AF （all P<0.05）. The multivariate Logistic regression analysis showed that hyperglycemia was a risk factor for AF （odds ratio = 1.753， 95% confidence interval ［CI］： 1.017　—　3.023， P=0.043）. The survival analysis showed that hyperglycemia increased the risk of ESLD （χ²=4.340， P=0.037）. The multivariate Cox regression analysis confirmed that hyperglycemia was a significant metabolic risk factor for ESLD in patients with AF （adjusted hazard ratio=3.208， 95%CI： 1.201　—　8.568， P=0.020）. ConclusionHyperglycemia can increase the risk of AF and ESLD in CHB-SLD patients. Clinical monitoring and active management should be strengthened for patients who have already developed AF and hyperglycemia.

[Objective] To conduct serological identification and molecular mechanism study on a ambiguous ABO blood group. [Methods] Standard serological techniques were used for the forward and reverse typing of ABO blood type. ABO gene coding and regulatory regions were analyzed by PCR after DNA extraction. Monoclonal sequencing was used to detect the haplotypes of the DNA sequence, and bioinformatics analysis was applied to predict the possible translation outcomes of the mutated DNA sequence. [Results] The sample’s red blood cells showed mixed field agglutination with anti-A, and the serum agglutinated with B cells, exhibiting serological characteristics of subtype A. Direct sequencing and monoclonal sequencing analysis of the ABO gene confirmed one allele as O02, the other had a c.27delC mutation compared with A102, which could cause the translation sequence to terminate prematurely at the 19th amino acids. Analysis and prediction suggested that the mutation might affect the function of the transferase through mechanisms such as shifting the initiation codon, altering the reading frame and affecting the splice sites. [Conclusion] This case is a rare A subtype caused by the c.27delC variation, and the impact on the glycosyltransferase may involve multiple mechanisms, which require further research and exploration.

Lipid rafts are microdomains in the cell membrane that are involved in cell signal transduction,metabolism,and intercellu-lar interactions.In recent years,studies have shown that lipid rafts play an important role in the pathogenesis of diabetes.Cholesterol and sphingolipids are the main lipid components in lipid rafts,and the protein components in lipid rafts include caveolin,flotillin,pal-mitoylated proteins,and glycosylphosphatidylinositol-anchored proteins.Changes in these components affect the structure and function of lipid rafts,which in turn may affect insulin signal transduction,leading to the occurrence of diabetes-related diseases.Lipid rafts are closely related to the occurrence and development of diabetes in different tissues.Pancreatic lipid rafts are closely related to insulin se-cretion,and their structural changes affect insulin synthesis and release.Changes in lipid rafts in adipose tissue are related to insulin resistance and disorders of glycolipid metabolism.Changes in lipid rafts in the liver can affect gluconeogenesis and glycogen synthesis.Lipid rafts in the kidney play a regulatory role in the progression of diabetic nephropathy.This article aims to provide a comprehensive overview of the role of lipid rafts in the pathogenesis of diabetes,offering insights into the identification of new targets for the prevention and treatment of diabetes in the future,as well as presenting a new perspective for the development of therapeutic agents for diabetes.

The P2X7 receptor,a ligand-gated ion channel in the purinergic receptor family,is widely ex-pressed in various tissues and organs.Its structure is significantly different from other subtypes.This struc-tural specificity confers low adenosine triphosphate(ATP)binding affinity and two distinct characteristics:ion channel function under short-term/low-concentration ATP stimulation,and formation of non-selective pores with current facilitation during prolonged/high-concentration ATP exposure.Inflammatory responses are in-volved in the pathophysiological processes of various cardiovascular diseases.Substantial evidence indicates that P2X7 receptor activation participates in the pathophysiological processes of myocardial infarction,athero-sclerosis,hypertension,and cardiomyopathy..Receptor activation potentiates chronic inflammatory cascades,mechanistically contributing to myocardial infarction,atherosclerosis,hypertension,and cardiomyopathy pro-gression.This review summarizes the structure and function of P2X7 receptors and their mechanisms in vari-ous cardiovascular diseases.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease affecting the colon(particularly the descending colon and sigmoid)and rectum.UC primarily presents with persistent or recurrent diarrhea,abdominal pain,bloody stools,and other symptoms.The primary pathological mechanism of UC involves intestinal barrier injury.When the intestinal barrier function is compromised,characterized by loss of epithelial layer integrity,thinning of the mucus layer,and microbiota dysregulation,pathogenic microorganisms can infiltrate the lamina propria from the intestinal lumen through the damaged barrier,triggering and exacerbating the intestinal inflammatory response.Current treatments for UC are limited by high costs,numerous adverse reactions,and a high likelihood of relapse.Consequently,there is an urgent need for the development of new drugs that can effectively and safely treat UC.Natural products have become significant research targets in treating various diseases due to their broad biological activity,multiple action targets,low toxicity,and easy availability.They play a crucial role in the targeted repair of the intestinal barrier,with potential mechanisms including enhancing intes-tinal epithelial cells and their secreted proteins,regulating gut microbiota and its metabolism,and balancing immune cell subsets.Additionally,it is essential to consider the synergistic effects,bioavailability,and safety of natural products.This paper summarizes the natural products reported in the past five years for their anti-UC properties by repairing the intestinal barrier,providing a theoretical basis for the development and application of natural products in anti-UC drugs.

Objective To investigate the application effect of cluster management in peri-discharge period of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods Using random number table method,90 patients with AECOPD were divided into the observation group(45 cases)and the control group(45 cases).All patients underwent active treatment after admission.During the peri-discharge period,the control group received routine management,while the observation group received cluster management based on internet chronic obstructive pulmonary disease(COPD)management platform.Both groups received 12 weeks of intervention.Comparisons were made between the two groups in terms of the degree of dyspnea[modified British Medical Research Council dyspnoea scale(mMRC)dyspnoea scale],pulmonary function[forced expiratory volume in the first second as a percentage of predicted value(FEV1%pred)],exercise endurance[6-minute walk test(6MWT)],management effect(frequency of emergency infusion or hospitalization due to moderate to severe acute exacerbation,frequency of multidisciplinary outpatient follow-up,compliance with regular home-based rehabilitation and proportions of smokers before and after intervention),and levels of laboratory indices[hemoglobin(Hb)and albumin(Alb)].Results After intervention,mMRC score of the observation group decreased and was lower than that of the control group(P＜0.05).The observation group showed an increase in FEV1%pred and 6 MWT distance,both of which were superior to those in the control group(P＜0.05).The proportion of smokers and number of emergency infusions or hospitalization diagnosis and treatment due to moderate-severe acute exacerbation in the observation group were lower than those in the control group.The proportion of regular home-based rehabilitation and multidisciplinary outpatient follow-up visits were higher/more in the observation group than those in the control group(P＜0.05).The levels of Hb and Alb in the observation group increased compared to those before intervention and were higher than those in the control group.Hb level in the control group decreased compared to that before intervention(P＜0.05).Conclusion Implementing cluster management during the peri-discharge period of patients with AECOPD can effectively alleviate dyspnea,improve exercise endurance,reduce acute exacerbation risk and promote the development of healthy behaviors.

Objective To investigate the effect of naringenin(NAR)on right ventricular remodeling induced by hypoxic pulmonary hypertension(HPH)and its related mechanism.Methods SD rats were randomly divided into the control group(NC),the NC+NAR group,the HPH group and the HPH+NAR group,with 15 rats in each group.HPH model was established in a low-pressure hypoxic artificial chamber.After the successful construction of the model,rats in the NC+NAR group and the HPH+NAR group were given NAR 100 mg/(kg·d)gavage once a day for 4 weeks,while rats in the NC group and the HPH group were given the same volume of normal saline once a day for 4 weeks.Right ventricular free wall thickness(RVEDWT)and end-diastolic right ventricular diameter(RVEDD)were measured by echocardiography.Right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)were measured by cardiac catheter.Right ventricular mass ratio(RV/BW)and right ventricular hypertrophy index(RVHI)were calculated.Masson and Sirius staining of right ventricle was used to calculate the collagen volume fraction(CVF).TUNEL staining was used to evaluate the apoptosis of right ventricular cardiomyocytes.The contents of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in right ventricular myocardium were detected.The expression of Rho associated kinase(ROCK)protein was detected by Western blot assay.Results Compared with the NC group and the NC+NAR group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content and ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were increased in the HPH group.RVEDD and SOD activity in right ventricular myocardium were decreased(P＜0.05).Compared with the HPH group,mPAP,RVSP,RVEDWT,RV/BW,RVHI,right ventricular CVF,right ventricular myocardial cell apoptosis rate,MDA content,ROCK1 and ROCK2 protein expression in right ventricular myocardial tissue were decreased in the HPH+NAR group,and RVEDD and SOD activity in right ventricular myocardium were increased(P＜0.05).Conclusion NAR can reduce HPH-induced right ventricular remodeling,and its mechanism may be related to inhibiting ROCK signaling pathway and further improving apoptosis and oxidative stress in right ventricular myocardium.

Objective:To investigate the mechanism by which microRNA-183 (miR-183) regulates the progression of diabetic nephropathy (DN) through targeting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and modulating the AKT signaling pathway, and to identify potential therapeutic targets for DN.Methods:(1) Bioinformatic analysis of miRNA expression: MiRNA expression datasets from diabetic nephropathy (DN) and control samples were obtained from the Gene Expression Omnibus database. Differential expression analysis was performed, and differentially expressed miRNAs (DEmiRNAs) were identified using thresholds of an absolute log 2 (fold changes) >1 and an adjusted P-value<0.05. The results were visualized in a volcano plot and a heatmap. (2) Animal model establishment and in vivo interventional studies: A DN rat model was induced by administration of a high-fat/high-sucrose diet combined with an intraperitoneal injection of streptozotocin. Rats were randomly assigned into four groups ( n=10 per group) using a random number table: control group, DN model group, miR-183 inhibitor negative control (NC) group, and miR-183 inhibitor group. The latter two groups received tail vein injections of the miR-183 inhibitor NC or the miR-183 inhibitor, respectively, for eight consecutive weeks. Parameters including fasting blood glucose, 24-hour urinary protein excretion, urinary albumin excretion rate (UAER), serum creatinine, and blood urea nitrogen (BUN) were measured. Renal histopathological changes were assessed by HE and PAS staining. Furthermore, the expression of candidate miRNAs from patient data was validated, and the mechanism of action of miR-183 was investigated using quantitative real-time PCR and Western blotting. (3) In vitro mechanistic investigations in cultured podocytes: Mouse podocyte clone-5 (MPC5) cells were cultured in vitro and subjected to the following conditions: normal glucose (5.3 mmol/L glucose), high glucose (30 mmol/L glucose), and osmotic control (5.3 mmol/L glucose+19.5 mmol/L mannitol). Cells in the logarithmic growth phase were transfected with the miR-183 inhibitor (100 nmol/L), miR-183 mimic (50 nmol/L), or their corresponding negative controls. A dual-luciferase reporter assay was conducted to validate the binding interaction between miR-183 and the 3'-untranslated region (3'UTR) of PTEN. The effects of miR-183 on the AKT signaling pathway, apoptosis-related proteins, and cell viability were evaluated by quantitative real-time PCR, Western blotting, and the cell counting kit-8 assay, respectively. Results:MiR-183 expression was markedly upregulated in renal tissues from DN patients and DN model rats (both P<0.05). Inhibition of miR-183 significantly reduced renal miR-183 levels by 90.2% ( P<0.01), decreased fasting blood glucose by 65.3% ( P<0.01), and improved renal function parameters, including reductions in urinary protein (40.3%), blood urea nitrogen (32.1%), urinary albumin excretion rate (22.5%), and serum creatinine (40.2%) (all P<0.01). Histological analyses showed attenuation of glomerular lesions and glycogen accumulation. Bioinformatic prediction and experimental validation identified PTEN as a direct target of miR-183, confirmed by dual-luciferase assays. In vitro, miR-183 inhibition increased PTEN expression, reduced AKT phosphorylation, promoted podocyte proliferation, and suppressed apoptosis (upregulation of Bcl-2 and downregulation of cleaved-caspase-3). These effects were abolished upon PTEN knockdown. Conclusions:miR-183 aggravates DN by targeting PTEN and activating the AKT signaling pathway. Inhibition of miR-183 improves renal function and reduces podocyte apoptosis, suggesting miR-183 as a potential therapeutic target for DN.

Objective To investigate the mechanism of action of the nuclear factor erythroid 2-related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)signaling pathway in non-alcoholic fatty liver disease(NAFLD),and to explore the mechanism of Gegen QinLian Decoction for the treatment of NAFLD,using in vivo and in vitro experiments.Methods Rats were fed with high-fat chow for 24 weeks to induce NAFLD,and were then divided randomly into normal(C),model(M),high-,medium-,and low-dose Gegen QinLian Decoction(GGQLT-H,GGQLT-M,GGQLT-L),and metformin(Met)groups.From week 25 onwards,the rats were administered the corresponding drugs by gavage for 2 weeks according to the grouping,until sampling.Levels of the oxidative stress markers malondialdehyde(MDA)and glutathione(GSH)in the liver tissues were measured in each group using biochemical kits and ferrous iron(Fe2+)in rat liver tissues was detected using a Fe2+kit.Nrf2,heme oxygenase-1(HO-1),SLC7A11,glutathione synthetase(GSS),GPX4,and acyl coenzyme A synthetase 4(ACSL4)mRNA levels in rat liver tissues were measured by reverse transcription quantitative polymerase chain reaction.For cellular experiments lipid acc umulation was induced in HepG2 hepatocellular carcinoma cells using 1 mmol/L free fatty acid,to mimic the NAFLD in vitro model.Different concentrations of Gegen QinLian Decoction and metformin-containing serum were added for treatment.Lipid accumulation was detected in the cells in each group by Oil red O staining.The MDA and GSH contents of HepG2 cells in the different groups were determined using appropriate kits,and the ferrous contents were detected using a cell-specific ferrous kit.Expression levels of Nrf2,HO-1,SLC7A11,GSS,GPX4,and ACSL4 mRNA was detected in each group of cells using reverse transcription quantitative polymerase chain reaction.Results In the animal experiments,MDA and Fe2+liver levels were significantly higher in the M group than in the C group,while GSH levels were significantly lower(P＜0.01).GGQLT-H,GGQLT-M and Met groups showed significantly reduced MDA and Fe2+and elevated GSH levels compared with the M group(P＜0.01,P＜0.05).High-and medium-dose Gegen QinLian Decoction and metformin increased Nrf2,HO-1,GSS,and GPX4 mRNA and decreased ACSL4 mRNA expression levels(P＜0.01,P＜0.05).In cellular experiments,lipid droplets were significantly increased in the HepG2 cell M group compared with those in the C group,and lipid droplets were significantly reduced by Gegen QinLian Decoction and metformin.MDA and Fe2+levels were significantly increased and GSH levels were significantly decreased in the HepG2 M group compared with the levels in the C group(P＜0.01),while all doses of Gegen QinLian Decoction and metformin significantly decreased MDA and Fe2+levels(P＜0.01)and increased the GSH content(P＜0.01,P＜0.05).Nrf2,GSS,GPX4,and SLC7A11 mRNA expression levels in the GGQLT-H group,Nrf2,HO-1,and SLC7A11 in the GGQLT-L group,HO-1,SLC7A11,and GSS in the GGQLT-M group,and GSS,Nrf2,and HO-1 in the Met group were all significantly increased compared with the findings in the M group(P＜0.01,P＜0.05).ACSL4 mRNA expression levels were significantly decreased in the GGQLT-M and GGQLT-L groups and the Met group(P＜0.01,P＜0.05).Conclusions Gegen QinLian Decoction can improve NAFLD by inhibiting ferroptosis,and its mechanism may he related to regulation of the Nrf2/SLC7A 11/GPX4 signaling pathway.

Objective:To investigate the application effect of team-based learning (TBL) versus lecture-based learning (LBL) in the first aid skill training of peacekeeping forces.Methods:A total of 326 officers and soldiers who had not participated in first aid skill training from various peacekeeping units in the Gao area of the Eastern Theater of United Nations Multidimensional Integrated Stabilization Mission in Mali from September 2022 to June 2023 were selected and divided into groups A and B using numerical randomization, with 163 individuals in each group. The individuals in group A received LBL teaching, and those in group B received TBL teaching. Questionnaire survey, theoretical assessment, and operational skill assessment were performed for all officers and soldiers after the end of the course. SPSS 19.0 was used for the t-test and the chi-square test. Results:Compared with the LBL group, the TBL group had significantly better first aid awareness, first aid skills, team collaboration ability, and humanistic concern and a significantly higher degree of satisfaction with the training mode. The LBL group had a slightly higher theoretical assessment score than the TBL group [(86.73±8.57) vs. (85.92±7.66)], with no significant difference between the two groups. Compared with the LBL group, the TBL group had significantly better scores of each operational skill and the total score of operational skill assessment [(86.71±11.25) vs. (81.14±10.05)].Conclusions:As a relatively effective training mode, the TBL teaching method has significant advantages in improving the first aid awareness, team collaboration ability, and practical operation ability of peacekeeping personnel, and therefore, it holds promise for application in Mali and other peacekeeping task areas.