AIM:To investigate the mechanism by which interleukin-13(IL-13)influences vascular smooth muscle cell(VSMC)phenotypic transformation and subsequently contributes to vascular intimal hyperplasia in rats.METHODS:A total of 32 male SD rats,aged 5～7 weeks and weighing 330～360 g,were randomly divided into 4 groups(n=8 per group):normal(Nor)group,normal treatment(Nor+IL-13 neutralizing antibody,Nor+IL-13Nab)group,inju-ry(Inj)group,and injruy treatment(Inj+IL-13Nab)group.A 2F balloon catheter was used to induce mechanical injury in the left common carotid artery of SD rats to establish a vascular intimal hyperplasia model.Hematoxylin-eosin staining was performed to observe vascular structural changes.Enzyme-linked immunosorbent assay(ELISA)kits were used to measure IL-13 and transforming growth factor-β1(TGF-β1)levels.Human aortic smooth muscle cells(HA-SMCs)were cultured in vitro.Flow cytometry was conducted to assess peripheral blood CD4+IL-13+T cell content.Real-time quantita-tive PCR(RT-qPCR)was employed to evaluate gene expression levels of α-smooth muscle actin,osteopontin,calponin,collagen type Ⅰ/Ⅲ,proliferating cell nuclear antigen and Ki-67 antigen.Transwell and scratch wound assays were per-formed to assess cell migration.RESULTS:Compared with the model group,administration of IL-13Nab significantly in-hibited vascular intimal hyperplasia induced by mechanical vascular injury by antagonizing high plasma IL-13 levels(P<0.01).Immunofluorescence and mRNA analysis showed that neutralizing high plasma IL-13 suppressed collagen accumu-lation(P<0.01)and VSMC phenotypic transformation(P<0.01)in the injured vessels but did not inhibit peripheral blood CD4+IL-13+T cell activation.Incubation of HA-SMCs with recombinant human IL-13(rhIL-13)promoted cell pro-liferation and migration(P<0.01)as well as phenotypic transformation(P<0.01).Additional evidence suggested that rhIL-13-induced HA-SMC phenotypic transformation was associated with the regulation of TGF-β1 secretion by HA-SMCs.CONCLUSION:Interleukin-13 promotes vascular intimal hyperplasia by regulating VSMC phenotypic transformation through TGF-β1 secretion in rat models.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced athero-sclerosis in ApoE-/-mice.Methods Twenty-four ApoE-/-mice were randomly divided into the normal group,high-fat group,and high-fat+anti-PD-L1 mAb group.After 70 days,the blood samples were harves-ted.Blood vessels(aortic root to abdominal aorta)and liver from each groups were stained with Oil Red O.Hematoxylin-eosin staining(HE)was employed to vis-ualize structural changes in liver.Enzyme-linked im-munosorbent assay(ELISA)was applied to detect the serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)and inflammatory factors(IFN-γ,TNF-α,IL-1 β).Flow cytometry was used to detect the proportion of lymphocytes(CD4 and CD8).RT-PCR was utilized to assess the expressions of IFN-γ,TNF-α,IL-1 β,CD4 and CD8 in liver.Results Compared with the high-fat group,the treatment with anti-PD-L1 monoclonal antibody promoted vascular wall and liver lipid accumulation,and also up-regulated serum and liver content of cholesterol(CHO),triglyceride(TG)and high-density lipoprotein(HDL-c).Treatment with anti-PD-L1 monoclonal antibody up-regulated the con-tent of alanine aminotransferase(GPT)and aspartate aminotransferase(GOT)in serum and liver,but not al-kaline phosphatase(AKP).ELISA test indicated that treatment with anti-PD-L1 monoclonal antibody stimu-lated the serum level of IFN-γ,TNF-α and IL-1 β.Fur-thermore,the mRNA level of IFN-γ,TNF-α and IL-1 βin liver was also up-regulated after treatment with anti-PD-L1 monoclonal antibody.With flow cytometry,we observed that treatment with anti-PD-L1 monoclonal antibody promoted hepatic CD8+T and CD8+IFN-γ+T cell activation,but had no effect on CD4+IFN-γ+T cell activation under high-fat feeding conditions.Con-clusions Anti-PD-L1 monoclonal antibody adminis-tered under high-fat feeding conditions can damage liv-er function and aggravate atherosclerosis by activating liver CD8+IFN-γ+T cells.

Genistein is a naturally occurring compound widely found in leguminous plants and is the primary active ingredient in traditional Chinese medicinal herbs such as Astragalus,Puer-aria lobata(Kudzu),Fagopyrum esculentum(Buckwheat),and Rhodiola.Modern pharmacological research indicates that genistein possesses a variety of biological activities,including anti-inflammatory,antioxidant,antitumor,lipid-lowering,an-tidiabetic,anti-ultraviolet,and neuroprotective effects.There-fore,by summarizing and generalizing the pharmacological ac-tions and mechanisms of genistein,it is hoped to provide a basis for its clinical application and drug development.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Helicobacter pylori(H.pylori)infection is a prevalent global health issue that can lead to indiges-tion,peptic ulcer disease,and gastric cancer.With ongoing research advancements,significant progress has been made in the eradication of H.pylori.Based on these important findings from North America,the American College of Gastroenterology(ACG)has released updated clinical practice guideline(CPG),published in the American Journal of Gastroenterology in September 2024.Compared to previous guidelines,key updates include:increased resistance rates to critical antibiotics used for H.pylori treatment,such as clarithromycin and levofloxacin,which have reduced the efficacy of common treatment regimens containing these antibiotics;and research on novel treat-ment options for newly diagnosed patients,including new antibiotic alternatives(e.g.,rifampicin)or more potent next-generation gastric acid inhibitors(e.g.,potassium-competitive acid blockers,PCABs).These updates provide the latest evidence and reference for the clinical management of H.pylori infection.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Objective To investigate the risk factors associated with the coexistence of Sj?gren's syndrome(SS)in patients with primary biliary cholangitis(PBC),and to develop and compare diagnostic prediction models for the comorbidity of the two conditions.Methods A total of 183 patients first diagnosed with PBC at The First Affiliated Hospital of Soochow University from January 2012 to April 2023 were included.They were divided into two groups based on the presence or absence of SS:those with PBC alone(n=96)and those with PBC accompanied by SS(n=87).Clinical manifestations,serological antibody results,and laboratory parameters were compared between the two groups.Continuous data were compared using the t-test or Mann-Whitney U test,while categorical data were compared using the chi-square test.The risk factors for the presence of SS in PBC were identified through a multivariable Logistic regression analysis.Subsequently,an artificial neural network(ANN)model and a multiple logistic regression(MLR)model were constructed to predict the presence of SS in PBS.The receiver operating characteristic curve was plotted in MedCalc,and the area under the curve(AUC)was compared using the Delong test.Results Serum IgG level(odds ratio[OR]=1.600,95%confidence interval[CI]:1.364-1.876,P<0.001)was an independent risk factor,while serum total bilirubin level(OR=0.760,95%CI:0.700-0.811,P=0.005)was an independent protective factor against the presence of SS in patients with PBC.The AUCs of the ANN model and the MLR model diagnosing SS in PBC were 0.919(95%CI:0.870-0.954)and 0.896(95%CI:0.843-0.936),respectively,both showing good predictive efficacy,and the predictive efficacy of the ANN model was significantly better than that of the MLR model(P=0.019 2).Conclusion Patients with PBC complicated by SS usually present at an early stage with mild symptoms during their initial medical consultation,when early diagnosis and treatment are beneficial for their prognosis.For patients with PBC showing high serum IgG levels at the first diagnosis or consultation,SS screening is necessary.

Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced athero-sclerosis in ApoE-/-mice.Methods Twenty-four ApoE-/-mice were randomly divided into the normal group,high-fat group,and high-fat+anti-PD-L1 mAb group.After 70 days,the blood samples were harves-ted.Blood vessels(aortic root to abdominal aorta)and liver from each groups were stained with Oil Red O.Hematoxylin-eosin staining(HE)was employed to vis-ualize structural changes in liver.Enzyme-linked im-munosorbent assay(ELISA)was applied to detect the serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)and inflammatory factors(IFN-γ,TNF-α,IL-1 β).Flow cytometry was used to detect the proportion of lymphocytes(CD4 and CD8).RT-PCR was utilized to assess the expressions of IFN-γ,TNF-α,IL-1 β,CD4 and CD8 in liver.Results Compared with the high-fat group,the treatment with anti-PD-L1 monoclonal antibody promoted vascular wall and liver lipid accumulation,and also up-regulated serum and liver content of cholesterol(CHO),triglyceride(TG)and high-density lipoprotein(HDL-c).Treatment with anti-PD-L1 monoclonal antibody up-regulated the con-tent of alanine aminotransferase(GPT)and aspartate aminotransferase(GOT)in serum and liver,but not al-kaline phosphatase(AKP).ELISA test indicated that treatment with anti-PD-L1 monoclonal antibody stimu-lated the serum level of IFN-γ,TNF-α and IL-1 β.Fur-thermore,the mRNA level of IFN-γ,TNF-α and IL-1 βin liver was also up-regulated after treatment with anti-PD-L1 monoclonal antibody.With flow cytometry,we observed that treatment with anti-PD-L1 monoclonal antibody promoted hepatic CD8+T and CD8+IFN-γ+T cell activation,but had no effect on CD4+IFN-γ+T cell activation under high-fat feeding conditions.Con-clusions Anti-PD-L1 monoclonal antibody adminis-tered under high-fat feeding conditions can damage liv-er function and aggravate atherosclerosis by activating liver CD8+IFN-γ+T cells.