Type 2 diabetes mellitus(T2DM)is an insulin resistance disease.Improving insulin resis-tance and controlling blood glucose are the main means of clinical treatment for T2DM.Empa-gliflozin is a highly selective sodium-dependent glu-cose transporters(SGLT)2 inhibitor,which is inde-pendent of insulin.It can effectively control blood glucose levels,reduce blood pressure and body weight,protect heart and kidney function,reduce the rehospitalization rate and the risk of death in patients with heart failure(HF),and does not in-crease the risk of hypoglycemia.Empagliflozin can be used alone or in combination with other hypo-glycemic drugs to control blood glucose.This arti-cle reviews the mechanism of action,clinical bene-fits,and combination with other drugs of empa-gliflozin,aiming to provide reference for the clinical use of empagliflozin.

Depression is a common mental dis-ease.At present,there are poor efficacy and drug-related safety problems in antidepressant treat-ment.Toludesvenlafaxine,as a new triple reuptake inhibitor(TRIs/SNDRIs),increases the inhibitory ef-fect of dopamine(DA)reuptake on the basis of se-rotonin(5-HT)and norepinephrine(NE),achieves multi-target synergistic therapy and reduces 5-HT/NE-related adverse drug reactions.This article re-views the basic introduction,preclinical research,clinical efficacy and safety of toludesvenlafaxine,in order to provide more ideas and options for the treatment of depression.

The platelets play the important role in tumor angiogenesis,growth,and metastasis,in addition to coagulation.The interaction between tumors and platelets can produce"tumor-induced platelets",which leads various changes of platelet characteristics.In addition,activated platelets can also inhibit the effects of both chemotherapy and immunotherapy,therefore,both inhibiting platelet activation and depleting platelets can effectively improve tumor prognosis.In this review,we intro-duced the key role of platelets in the development of tumors,summarized their application in tumor diagnosis,monitoring,and treatment,and provid-ed our view on how to develop precise delivery strategies based on platelets for achieve efficient and safe tumor treatment.

AIM:To explore the mechanism of berberine on breast cancer cells based on network pharmacology and in vitro cell experiments.METH-ODS:Firstly,berberine and breast cancer were tak-en as the research objects,the intersection targets of the two were screened by VEEN diagram,GO function and KEGG enrichment analysis were per-formed by R language,and molecular docking and visualization were carried out by Autodock Vina and Pymol software.Then,berberine treated breast cancer MCF-7 cells for 24 h,and then in vi-tro cell experiments were performed.CCK-8 was used to detect cell viability,Edu and plate cloning were used to detect cell proliferation and cloning,and apoptosis was detected by An-nexin V-FITC/PI double staining and Western blot.Laser confocal and CETSA were used to verify the binding effect of berberine and AKT1 protein.RESULTS:The results of network pharmacology showed that berberine had a good binding to the core targets AKT1,AKT2 and MAPK3.Berberine(20,40,80 μmol/L)signifi-cantly inhibited the proliferation and cloning ability of MCF-7 cells in a concentration-dependent man-ner(P＜0.05,P＜0.01).The results of laser confocal and CETSA experiments showed that berberine and AKT1 had a binding effect,and the stability of the two was enhanced after the combination.CONCLU-SION:Berberine inhibits MCF-7 cell proliferation and induces apoptosis in human breast cancer cells by targeting binding to AKT1 protein.

AIM:To explore the way and mecha-nism of cell death induced by Fructus Akebiae in non-small cell lung cancer(NSCLC)cells.METH-ODS:CCK-8,Hochest33342/PI staining,and colony formation experiments were used to detect cell via-bility and proliferation.Western blot was used to detect the expression of cell death-related proteins ATG5,HMGB1,GPX4,apoptosis-related proteins,and PI3K-Akt signaling pathway-related proteins.Flow cytometry was used to detect the apoptosis rate.DCFH-DA fluorescent probes were used to de-tect the levels of total intracellular ROS under a flu-orescence microscope.RESULTS:Fructus Akebiae significantly inhibited the cell viability and prolifera-tion of human NSCLC cells(P＜0.05).The expression of apoptosis-related proteins BAX,Cleaved cas-pase3,and Cleaved caspase9 in NSCLC cells was sig-nificantly increased(P＜0.05),while p-PI3K,p-Akt,and BCL2 were markedly decreased(P＜0.05).Fruc-tus Akebiae was found to clearly increase the apop-tosis rate and the levels of total intracellular ROS(P＜0.05).The antioxidant NAC significantly reversed apoptosis,ROS production and regulation of PI3K-Akt pathway related proteins induced by Fructus Akebiae(P＜0.05).CONCLUSION:Fructus Akebiae in-duces apoptosis via regulating ROS-mediated PI3K-Akt signaling pathway in non-small cell lung cancer cells.

AIM:To investigate the clinical effects of tirofiban and butylphthalide combined with stent thrombectomy in the treatment of patients with acute cerebral infarction in the ultra-time win-dow.METHODS:A total of 100 patients with ACI beyond time window admitted to our hospital from January 2021 to January 2023 were randomly grouped into the control group(50 cases,treated with stent thrombectomy)and the study group(50 cases,treated with tirofiban and butylphthalide combined with stent thrombectomy),clinical data of patients were collected,and the clinical efficacy,blood lipid levels,coagulation function,neurologi-cal function,quality of life,and incidence of ad-verse reactions were compared between the two groups.RESULTS:Compared with the control group,the total effective rate of the study group obviously increased(P＜0.05).Before treatment,there was no obvious difference between the two groups in triacylglycerol(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),prothrom-bin time(PT),activated partial thromboplastin time(APTT),D-dimer(D-D),fibrinogen(FIB),NIHSS score and Barthel index scale(BI)score of patients with ACI beyond time window(P＞0.05).After treat-ment,the TG,TC,LDL-C,FIB,D-D,and NIHSS score of ACI patients in both groups decreased(P＜0.05),while HDL-C,PT,APTT,and BI score increased(P＜0.05),and the above indicators improved more ob-viously in the study group(P＜0.05).There was no obvious difference in the total incidence of adverse reactions between the two groups(P＞0.05).CON-CLUSION:The combination of tirofiban and bu-tylphthalide with stent thrombectomy in the treat-ing ACI beyond time window has a definite effect,which can improve the blood lipid level,coagula-tion function and neurological function of patients,and help to improve the quality of life of patients,with good safety.

The immunosuppressive tumor micro-environment significantly limits the efficacy of im-munotherapy.Tumor-associated macrophages(TAMs),the most abundant immune cells in the tu-mor microenvironment,often exhibit an immuno-suppressive M2 phenotype,contributing to this im-munosuppressive landscape.Modulating TAMs to adopt anti-tumor phenotypes can enhance immu-notherapy outcomes and inhibit tumor progression.In recent years,tumor immunotherapy leveraging engineered bacteria has garnered considerable at-tention.Bacteria possess the ability to target tu-mors,preferentially colonizing tumor regions,and contain abundant pathogen-associated molecular patterns that effectively activate TAMs within the immunosuppressive tumor environment.This acti-vation enhances the tumoricidal and clearance ca-pabilities of TAMs.With the rapid advancements in synthetic biology,engineered bacteria have emerged as a potent therapeutic modality for im-munotherapy,leading to increased focus on the regulation of TAMs by engineered bacteria.This pa-per first outlines clinical studies on targeted TAMs therapy and engineered bacteria-based tumor ther-apy.It then reviews recent advancements in bacte-rial regulation of TAMs,detailing how engineered bacteria enhance TAM recruitment,improve TAM phagocytosis,and remodel TAM phenotypes.Mod-ulating TAMs with engineered bacteria presents a promising therapeutic strategy and introduces a novel approach in tumor immunotherapy.

Rheumatoid arthritis is an autoim-mune disease characterized by progressive bone destruction,with joint swelling caused by synovial inflammation in the early stage,and joint deformi-ty caused by cartilage and bone destruction occur-ring in the middle and late stages as inflammation develops,resulting in a 75％disability and deformi-ty rate within three years,and the prevention and treatment of RA bone and joint destruction is of ur-gency,and it is therefore of great significance to search for effective drugs to treat RA bone destruc-tion.Studies have shown that wrinkled skin papaya can treat RA bone destruction,but the composition and mechanism of action are unknown,so this re-view aims to provide an overview of the mecha-nism of action of the effective active ingredients in wrinkled skin papaya for the treatment of rheuma-toid arthritis bone destruction,and to provide a ba-sis and direction for the development of novel for-mulations of traditional Chinese medicines for anti-RA bone destruction.

Artificial intelligence(AI)has emerged as a cutting-edge technology leading the future and is a key engine for China's development.In the innovation and research of medical devices,AI has provided critical support in the areas of intelligent diagnostic assistance,intelligent therapeutic assis-tance,intelligent monitoring,life support,et al.Ma-chine learning-enabled device software functions(ML-DSFs)have become an essential component of many medical devices.Recently,the United States Food and Drug Administration(FDA)released a draft guidance titled"Marketing Submission Rec-ommendations for a Predetermined Change Con-trol Plan for Artificial Intelligence/Machine Learn-ing(AI/ML)-Enabled Device Software Functions(Draft)."that aimed to provide a forward-looking approach to foster the development of ML medical devices.By supporting iterative updates through modifications,this approach ensures the continu-ous safety and effectiveness of the devices.This guidance represents the latest in regulatory direc-tion and is especially beneficial for enhancing the quality and efficiency of clinical trials for AI prod-ucts.Therefore,we plan to provide a detailed intro-duction and interpretation of the guidance,with the aim of learning from international advanced regulatory concepts and experiences to promote the development of ML-DSFs with more profound international influence.

Inflammatory lung diseases are cur-rently a major challenge threatening human health and life.Imbalanced inflammation and excessive in-flammation can lead to tissue damage and trigger the occurrence and development of systemic dis-eases.Anti-inflammatory treatment is of vital im-portance for improving patient survival and quality of life.In recent years,significant progress has been made in the exploration and research of drug targeting strategies,effectively addressing issues such as slow onset,low bioavailability,and rapid in vivo clearance rates during drug delivery.Drug tar-geting can increase local drug concentrations,re-duce dosing frequency,and mitigate side effects.This review primarily elaborates on the classifica-tion and characteristics of inflammatory lung dis-eases.It comprehensively reviews targeted drug de-livery strategies for inflammatory lung diseases from three perspectives:local targeting,passive tar-geting,and active targeting.Furthermore,it dis-cusses the prospects and challenges of drug target-ed therapy for lung diseases,potentially providing new research and application ideas for the target-ed treatment of inflammatory lung diseases.