AIM:To examine the impact of the transcription factor 7 analogue 2(TCF7L2)gene polymorphism on the hypoglycaemic effect of ex-enatide in patients with type 2 diabetes mellitus(T2DM).METHODS:A total of 100 newly diagnosed Han Chinese patients with T2DM who had not re-ceived any drug treatment were selected from the Affiliated Hospital of Xuzhou Medical University and treated with exenatide monotherapy for 6 months.The TCF7L2 rs290487 was genotyped by SnaPshot method,and blood glucose levels,lipids profiles and pancreatic function evaluation indica-tors were measured at baseline,3 months and 6 months after exenatide treatment.Multiple linear regression analysis was employed to assess the cor-relation between each indicator and the reduction in glycated hemoglobin(HbA1c)levels after 6 months of exenatide treatment.The expression of TCF7L2 protein in the plasma of T2DM patients was detected by enzyme-linked immunosorbent assay(ELISA)kit.Furthermore,western blotting was con-ducted to ascertain TCF7L2 expression in pancreat-ic tissues obtained from db/db mice and INS-1 cells cultured under high glucose conditions.Lentivirus transfection was used to overexpress or knock down TCF7L2 in insulinoma cell line(INS-1)cells,followed by measurement of KSIS activity and insu-lin content after a 24-hour intervention with exena-tide.RESULTS:The distribution pattern of TCF7L2 rs290487 was found to be in accordance with Har-dy-Weinberg equilibrium(P＞0.05).Following 6 months of exenatide treatment,there was a nota-ble reduction in blood glucose levels and an im-provement in lipid profiles when compared to base-line values.Additionally,there was a significant in-crease in the homeostasis model assessment of be-ta-cell function(HOMA-B)values.Patients with the TT genotype exhibited significantly lower postpran-dial plasma glucose(PPG)levels and HbA1c values compared to those with the CC or CT genotypes(P＜0.05).After adjusting for age,gender,body mass in-dex(BMI),and waist to hip ratio(WHR)in the mul-tiple linear regression model,a significant associa-tion was observed between the rs290487 TT geno-type,baseline HbA1c levels,and family history of diabetes with the reduction in HbA1c after six months of exenatide treatment(P＜0.05).Further-more,individuals with the rs290487 TT genotype demonstrated a notable elevation in TCF7L2 expres-sion in plasma among T2DM patients in comparison to those with the CC genotype(P＜0.05).In particu-lar,pancreatic tissue from db/db mice exhibited markedly elevated TCF7L2 expression compared to db/m mice.However,this up-regulation was re-versed by exenatide treatment.Similarly,INS-1 cells cultured under high glucose conditions dem-onstrated an increase in TCF7L2 expression,which was ameliorated upon exenatide administration.The knockdown of TCF7L2 using shRNA enhanced the KSIS function of pancreatic β cells and aug-mented the insulinotropic effect of exenatide.Con-versely,the upregulation of TCF7L2 impaired the KSIS function of pancreatic β cells and attenuated the insulinotropic effect of exenatide.CONCLU-SION:The TCF7L2 rs290487 gene polymorphism is closely associated with the hypoglycaemic efficacy of exenatide therapy.The risk allele C may diminish the effectiveness of exenatide by impacting the lev-els of PPG and HbA1c in T2DM patients.The muta-tion at TCF7L2 rs290487 site(C→T)influenced the expression of TCF7L2 protein.By exerting its regula-tory effect,exenatide may be capable of regulating the impact of TCF7L2 on the function of pancreaticβ cells.

With the continuous development of genomics and precision medicine,targeted therapy and immunotherapy targeting biomarkers have ush-ered in a new era of anti-tumor therapy.However,due to the heterogeneity of tumor cells and the variability of tumor microenvironment,there are still significant differences in response to the same drug even in patient populations with the same bio-marker enrichment.By combining omics data with drug sensitivity algorithms,the response of anti-tu-mor drugs can be predicted and transformed into personalized diagnosis and treatment strategies re-quired for precision medicine,which is expected to improve the effectiveness of anti-tumor drugs in clinical treatment.Currently,machine learning is one of the commonly used modeling algorithms for predicting the response of anti-tumor drugs.How-ever,due to differences in input data and algorithm construction methods,there is currently a lack of comprehensive literature review in this field.There-fore,this article provides a review of machine learning algorithms for predicting anti-tumor drug responses,summarizing publicly available cell ge-nome characterization datasets,machine learning algorithms,and evaluation indicators in drug re-sponse prediction,as well as the current situation and challenges faced in clinical applications,in or-der to provide methodological references for the main research problems and potential solutions of machine learning algorithms in the field of drug re-sponse prediction.

Claudin 18 isoform 2(Claudin18.2,CLDN18.2)is a crucial structural protein involved in cell-cell tight junctions.While its expression is limit-ed in normal tissues,it is specifically overexpressed in malignant tumors such as gastric cancer,pancre-atic cancer,and esophageal cancer,making it a promising therapeutic target for cancer treatment.Recent advances in CLDN18.2-targeted therapies have been encouraging,and studies suggest that CLDN18.2-positive gastric cancer may possess a unique immune microenvironment.This raises the potential for combining targeted therapies with im-mune activation to achieve synergistic effects,po-tentially improving treatment outcomes for pa-tients with advanced gastric cancer.This review will focus on the immune microenvironment character-istics of CLDN18.2-positive gastric cancer and sum-marize the current research and clinical trial prog-ress in targeted therapies combined with immune activation for this specific cancer type.

Cholangiocarcinoma(CCA)is a highly aggressive and heterogeneous biliary malignancy characterized by challenges in early diagnosis,limit-ed efficacy of traditional chemotherapy,and poor prognosis.Due to its significant heterogeneity at the genomic,epigenetic,and molecular levels,mo-lecular testing and targeted therapy have become increasingly important in CCA management,form-ing an integral part of the era of precision oncolo-gy.The development of next-generation sequenc-ing(NGS)has advanced research into the molecu-lar subtypes and therapeutic targets of CCA,includ-ing FGFR2 fusions/rearrangements,IDH1 muta-tions,and BRAF mutations.Recently,two phase Ⅲ clinical trials,TOPAZ-1 and KEYNOTE-966,have es-tablished the pivotal role of immunotherapy com-bined with chemotherapy in advanced CCA.While precision diagnosis and treatment in CCA have shown promising progress,this field remains in its exploratory phase and faces numerous challenges.This review summarizes recent advancements in the diagnosis,molecular targeted therapy,immuno-therapy,resistance mechanisms,and the develop-ment of novel strategies for CCA.

Hepatocellular carcinoma,as a com-mon malignant tumor,remains a serious global health problem.Traditional methods such as surgi-cal resection and chemotherapy have limited ef-fects in improving the prognosis of advanced hepa-tocellular carcinoma.With the deepening of re-search into molecular mechanisms,targeted thera-py has become an important direction for the treat-ment of hepatocellular carcinoma.In this review,we summarize the main targeted drugs and associ-ated therapeutic strategies for hepatocellular carci-noma,aiming to provide references and evidence for future related research.

The incidence of pancreatic cancer has been increasing each year,and the 5-year survival rate is still around 10%.Diagnosis and treatment strategies are major concerns in the industry.Gene sequencing and multi-omics research have revealed more signal pathways and actionable targets,offer-ing the potential for new targeted therapeutic drugs.However,current drug treatment for pancre-atic cancer still relies mainly on chemotherapy,and targeted therapy strategies are not yet fully devel-oped and require further discussion.As basic and translational research in pancreatic cancer advances and precision medicine develops,it is expected that targeted treatment for pancreatic cancer will be-come more precise and individualized in the future.This article discusses the current progress and fron-tiers of targeted treatment for pancreatic cancer.

Colorectal cancer(CRC)is one of the most common malignancies worldwide,although anti-angiogenic targeted agents such as bevacizum-ab have shown significant efficacy in the treatment of metastatic CRC,however,the emergence of drug resistance is still a key obstacle affecting the suc-cess rate of treatment and survival of patients.This article reviews the progress of anti-angiogenesis targeted drugs in the treatment of CRC,the mecha-nism of drug resistance and how to solve the prob-lem of drug resistance.

AIM:To study the mechanism of ac-tion of radix angelica sinensis and astragalus mong-holicus extract(RAS-AM)in inhibiting fibroblast transdifferentiation(CMT)and preventing radiation-induced myocardial fibrosis(RIMF)via the Jagged1/Notch1 pathway.METHODS:Sixty male Wistar rats were randomly divided into blank group,model group,benazepril hydrochloride group,low dose RAS-AM group,medium dose RAS-AM group,and high dose RAS-AM group,with 10 rats in each group.Except for the blank group,all other groups were induced with high-energy radiation at a dose of 38 Gy to establish RIMF models.The blank group and the model group received sterile distilled water by gavage,and the other groups received medica-tion for 4 weeks of intervention:benazepril hydro-chloride group(1.0 mg·kg-1·d-1),low dose RAS-AM group(150 mg·kg-1·d-1),medium dose RAS-AM group(300 mg·kg-1·d-1),and high dose RAS-AM group(600 mg·kg-1·d-1).The general condition of rats,the ultrastructure of myocardial tissue were observed using electron microscopy,changes in myocardial tissue fibers using Masson staining,and CMT related protein Vimentin and α-SMA expres-sion using immunohistochemical staining tech-niques.ELISA was used to detect serum inflammato-ry factors IL-6 and TNF-α in rats.The levels of cTnI and ST2,and the expression of Jagged1 and Notch1 were detected by Western blot.RESULTS:Com-pared with the blank group,the model group rats exhibited symptoms such as mental fatiguem an-orexiam and loose stools;The arrangement of some myofibrils in the myocardium is disordered,with dis-solution and breakage of myofibrilsm abnormal Z-line structure in some partsm disordered mitochon-drial arrangement,rupture of mitochondrial mem-branem,and rupture or disappearance of mitochon-drial ridge structure in some parts.A large amount of collagen fibers proliferate and deposit in the myo-cardium,and the fibrotic area significantly increases(P<0.01);The expression of myocardial tissue Vi-mentin α-SMA protein increased(P<0.05),while the expression of Jagged1 and Notch1 proteins de-creased(P<0.05);serum IL-6 and TNF-α,the expres-sion of inflammatory factors such as cTnI and ST2 in-creased(P<0.05).compared with the model group,the RAS-AM and benazepril hydrochloride groups showed varying degrees of improvement in general conditions;the pathological changes of myocardial ultrastructure have been improved,and myocardial fibrosis has been alleviated;The area of collagen fi-bers significantly decreased(P<0.01);Myocardial tis-sue Vimentin α-SMA protein expression decreased(P<0.05),while Jagged1 and Notch1 expression in-creased(P<0.05);Serum IL-6 and TNF-α,The expres-sion of inflammatory factors such as cTnI and ST2 decreased(P<0.05).CONCLUSION:RAS-AM may al-leviate RIMF by intervening in the Jagged1/Notch1 pathway to inhibit CMT.The specific mechanism still needs further investigation

AIM:To explore the protective effect of total flavonoids from rhododendron(TFR)on oxi-dative stress injury in the brain of rats subjected to cerebral ischemia/reperfusion(I/R).METHODS:For-ty male SD rats were randomly divided into 5 groups:sham operation group(Sham group),cere-bral ischemia-reperfusion group(MCAO group),and Cerebral Ischemia/Reperfusion with TFR treat-ment groups(TFR 50,100,200 mg/kg groups).The MCAO group and TFR-treated groups underwent ischemia/reperfusion surgery,and the TFR-treated groups received TFR intragastrically for 14 consecu-tive days following the ischemia/reperfusion injury.After 14 days,comparisons were made in terms of neurological function scores,serum inflammatory factors,oxidative stress indicators,and brain injury markers.Additionally,histological examination of brain tissue morphology using Hematoxylin and Eo-sin(HE)staining,observation of cerebral blood flow through cerebral blood flow imaging,and measurement of lactate dehydrogenase(LDH),neu-ron-specific enolase(NSE)activity in serum,inter-leukin-1(IL-1),interleukin-6(IL-6)levels,superox-ide dismutase(SOD)activity,malondialdehyde(MDA)content,nitric oxide(NO)content,and nitric oxide synthase(NOS)activity were performed.RE-SULTS:Compared to the Sham group,MCAO rats exhibited abnormal neurological function scores,severe damage to the microstructure of brain tis-sue,noticeable changes in brain morphology,ele-vated activities of LDH and NSE,increased levels of IL-1 and IL-6,elevated MDA content,and de-creased SOD,NOS activity,and NO content.In com-parison to the MCAO group,rats treated with TFR at doses of 50,100,and 200 mg/kg showed recov-ery of abnormal neurological function scores,re-duced damage to the microstructure of brain tis-sue,decreased activities of LDH and NSE,lowered levels of IL-1 and IL-6,reduced MDA content,and increased SOD,NOS activity,and NO content.CON-CLUSION:Total flavonoids from Rhododendron can protect against cerebral ischemia/reperfusion inju-ry,reducing oxidative stress levels.

AIM:To display the distribution of evi-dence in the field of Yiqifumai injection treatment for heart failure.METHODS:To retrieve relevant da-tabases such as CBM,CNKI,Wanfang,VIP,Co-chrane Library,PubMed,Embase,and Web of Sci-ence,and search for the China Clinical Trial Regis-try,ClinicalTrials.gov and collect clinical studies,sys-tematic evaluations,and guideline studies on the treatment of heart failure with Yiqifumai injection.The evidence map research method use a table to display the proportion of literature,sample size,co-morbidities,and quality evaluations of systematic evaluations.Use a pie chart to display the propor-tion distribution of research types,a line chart to describe publication trends,and a bubble chart to display the distribution of evidence.RESULTS:The overall number of articles on the treatment of heart failure with Yiqifumai injection is in a steady development stage.Clinical studies are mainly small sample,single center,short-term randomized controlled trials,with a sample size of 60-100 cases and an intervention duration of mostly 14 days.The underlying disease is mainly coronary heart dis-ease.Clinical research evidence tends to support the therapeutic effect of Yiqifumai injection com-bined with conventional Western medicine in im-proving heart failure patients'heart function and quality of life.However,there are also issues such as low overall quality of research,unreasonable clinical trial design,small sample size,incomplete selection of outcome indicators,low international recognition of certain outcome indicators,and lack of reporting on long-term outcomes The overall quality of randomized controlled trials andsystem-atic evaluation methodology is low.CONCLUSION:In the future,more large sample,multicenter clini-cal randomized controlled trials should be conduct-ed to obtain higher-level evidence-based medicine evidence to fully demonstrate the advantages of traditional Chinese medicine treatment,and pro-mote the common development of traditional Chi-nese medicine cardiology and evidence-based med-icine.