AIM:To investigate the effect and mechanism of panax notoginseng saponins(PNS)inhibiting the proliferation of pulmonary artery smooth muscle cells(PASMCs)in rats under the ef-fect of monocrotaline(MCT).METHODS:PASMCs cultured in vitro were randomly divided into the normal control(Control)group,the monocrotaline(MCT)group,the panax notoginseng saponins(PNS)group,the knockdown(M+Si ADAM10)group,the knockdown postconditioning(M+P+Si ADAM10)group,the overexpression(M+OE AD-AM10)group,and the overexpression postcondi-tioning(M+P+OE ADAM10)group.After the model was constructed,the cell viability of each group was measured using the CCK-8 assay,along with Western blot utilized to detect the expression of proliferating cell nuclear antigen(PCNA),disinteg-rin metalloproteinase 10(ADAM10),and notch ho-mology protein-3(Notch3)at the cellular neurogen-ic locus,respectively.RESULTS:Under the effect of MCT,the viability of PASMCs was significantly en-hanced(P<0.05 or P<0.01);0-400 mg/L PNS was not toxic to the viability of normal cells,and 100 mg/L PNS could significantly inhibit the MCT-in-duced viability(P<0.01).After the knockdown of ADAM10,the viability of PASMCs significantly de-clined(P<0.01),and the expression of PCNA protein was significantly decreased(P<0.05),evidently in the M+P+Si ADAM10 group.Meanwhile,the ex-pression of ADAM10 and Notch3 protein was signif-icantly decreased(P<0.05 or P<0.01),evidently in the M+P+Si ADAM10 group.After overexpression of ADAM10,the viability of PASMCs was significant-ly enhanced(P<0.01),the expression of PCNA pro-tein was significantly increased(P<0.01),the PCNA value was slightly higher(P>0.05),and the expres-sion of ADAM10 and Notch3 protein was signifi-cantly elevated(P<0.05)in the M+P+OE ADAM10 group.Additionally,PASMCs overexpressing AD-AM10 with concomitant PNS exhibited a significant decrease in the expression of PCNA protein com-pared with PASMCs knocking down ADAM10(P<0.01),and the expression of ADAM10 and Notch3 protein declined to varying degrees(P>0.05).CON-CLUSION:Panax notoginseng saponins can mitigate MCT-induced PASMCs proliferation in rats by inhib-iting the ADAM10/Notch3 signaling pathway.

Type 2 diabetes mellitus is a metabol-ic disease characterized by high blood sugar levels.Traditionally,amino acids are primarily viewed as the basic building blocks for proteins and peptide synthesis.However,in recent years,amino acids have gained increased attention as signaling mole-cules that play crucial roles in the maintenance and regulation of metabolic homeostasis.It has been found that there is a close correlation between the metabolism of branched-chain and/or aromatic amino acids and the occurrence or development of type 2 diabetes mellitus.Furthermore,there have been successive reports on the regulation mecha-nism involved.This article will focus on the meta-bolic processes,mechanisms and clinical value of branched-chain and aromatic amino acids in type 2 diabetes mellitus.It will also summarize and pro-vide an outlook on the current state of amino acid metabolism in the treatment of diabetes mellitus,with the aim of offering new ideas for the treat-ment of type 2 diabetes mellitus.

The nucleophosmin 1(NPM1)muta-tion is one of the most frequent subtypes in acute myeloid leukemia(AML).Under the conditions of FLT3-internal tandem duplications(FLT3-ITD)and/or DNMT3A co-mutations or adverse cytogenetics,the originally favorable prognosis will deteriorate.In recent years,studies have found that multiple endocrine neoplasia protein(Menin)inhibitors tar-geting Menin-KMT2A complex can downregulate the overexpression of leukemia causing genes HOX(homeotic gene)and MEIS1(myeloid ecotropic vi-ral integration site 1)in NPM1-mutated AML,dem-onstrating remarkable anti-leukemia activity.This article aims to review the mechanism and clinical research of Menin inhibitors,novel small molecule targeted drugs in NPM1-mutated AML,as well as the resistance mechanism of Menin inhibitors,hop-ing to provide promising approaches for the subse-quent treatment of NPM1-mutated AML patients.

AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuri-caemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg-1·d-1),and Origre sanzhou decotion low,medium and high-dosage groups(7.42,14.85,29.70 g·kg-1·d-1),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxa-late,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopatho-logical and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),inter-leukin-6(IL-6),and IL-1β were determined by enzyme-linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factor-κB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,dis-organised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serum levels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflam-matory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1β were significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflamma-tory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyper-uricaemia combined with gouty arthritis.

AIM:To explore the mechanism of ac-tion and clinical significance of NLRC4 in multiple myeloma by analyzing the relative expression and clinical significance of NLRC4 mRNA in bone mar-row fluid of patients with multiple myeloma(MM),so as to guide the formulation of disease treatment and the evaluation of clinical prognosis.METHODS:MMRF database and GTEx database were used to compare the expression and survival correlation of inflammatory bodies between myeloma patients and normal controls.Real-time fluorescent quanti-tative polymerase chain reaction(qPCR)was used to detect the expression of inflammatory bodies in bone marrow fluid of 26 newly diagnosed myeloma patients and 19 post-treatment myeloma patients and peripheral blood of 28 normal volunteers ad-mitted to the First Affiliated Hospital of Anhui Medi-cal University from January to September 2023.The mRNA expression differences of each inflammatory body and the correlation between NLRC4 inflamma-tory body expression and clinicopathologic fea-tures,inflammatory factor/chemokine expression of newly diagnosed patients were analyzed.RE-SULTS:Compared with the control group and the treatment group,the expression of inflammasome mRNA in the newly diagnosed group was increased except for NLRP3,and the expression of NLRC4 mRNA was significantly increased(P<0.01).The he-moglobin count,creatinine level and calcium ion level were linearly correlated with NLRC4 mRNA ex-pression level in newly diagnosed patients(P<0.05).The mRNA expression levels of IL-18,CCL-3 and NL-RC4 in newly diagnosed patients were linearly cor-related(P<0.05).CONCLUSION:NLRC4 inflammato-somes are highly expressed in MM,and promote the occurrence and development of tumor by pro-moting the production and release of inflammatory cytokines/chemokines IL-18 and CCL-3,which is of great significance for the formulation of treatment plan and clinical prognosis evaluation of multiple myeloma.

AIM:To explore the efficacy and safe-ty of fecal microbiota transplantation combined with immune checkpoint inhibitors(ICIs)for malig-nant tumor patients with failed multi line anti-tu-mor treatment and concomitant cachexia,and to explore the changes in blood immunity and intesti-nal microbial environment in patients.METHODS:Five patients with malignant tumors who failed multi line anti-tumor treatment were enrolled and treated with ICIs combined with fecal microbiota transplantation.The efficacy was evaluated every 2-3 cycles,and adverse reactions were observed.Fe-cal 16srRNA gene sequencing and serum immuno-logical indicators were dynamically detected.RE-SULTS:Except for one patient who died 2.5 months after transplantation due to excessive tumor bur-den at enrollment,the overall survival of the re-maining four patients were extended(7.4,8.3,28.5,52.3 months).One patient with multiple intra-cranial metastases of lung adenocarcinoma signifi-cantly reduced the intracranial metastasis after in-testinal microbiota transplantation and almost dis-appeared.The serum IL-2,IL-10,TGF-β and other indicators of patients increased rapidly and then slowly decreased with the increase of transplanta-tion time,and finally were higher than before trans-plantation,with statistical differences.16srRNA gene sequencing analysis revealed significant differ-ences in the overall distribution of gut microbiota in patients after transplantation,gradually ap-proaching healthy transplant donors.All patients did not experience grade 2 or above adverse reac-tions,and the safety was good.CONCLUSION:For patients with malignant tumors,the combination of fecal microbiota transplantation and immuno-therapy may improve their quality of life,serum im-mune environment,and intestinal microbiota com-position,have a positive impact on survival progno-sis,and are safe and controllable,opening up new treatment methods for end-stage patients.

Depression is a mental disease with in-creasing prevalence worldwide,which seriously en-dangers human health with high disability rate and high suicide rate.Epigenetics is an emerging genet-ic theory in the 21st century.Its main research con-tent is to regulate the process of gene transcription or translation and affect its function and character-istics without changing the DNA sequence.These include DNA methylation,histone modification,chromatin remodeling and non-coding RNA regula-tion.The nervous system is susceptible to changes in the activity of epigenetic modifiers,and an in-creasing number of studies have shown that genet-ics and environment play an important role in the development of depression.This review will focus on the epigenetic mechanisms of depression.

As phagocytic innate immune cells,macrophages interact with various tissue types and play an important role in immune defense,inflam-matory response and tissue remodeling.Macro-phages participate in the occurrence and develop-ment of disease by polarizing into classically acti-vated M1 type and substitutively activated M2 type,or more complex phenotypes,when the tis-sue microenvironment changes.This paper focused on the application of macrophage polarization in cardiovascular diseases,and introduces macro-phage origin and activation to propose the relation-ship between macrophage polarization and cardio-vascular diseases.Then,the strategies for targeted macrophage therapy were proposed to provide an important theoretical basis for improving the in-flammatory state of cardiovascular diseases.

AIM:To explore the causal association between the counts of five types of white blood cells—neutrophils,monocytes,eosinophils,baso-phils,and lymphocytes—and venous thromboem-bolism(VTE).METHODS:Mendelian randomization(MR)analysis method was used,with genetic vari-ants associated with the five types of white blood cells as instrumental variables,and venous throm-boembolism occurrence risk as the outcome vari-able,inverse variance-weighted(IVW)method was employed as the primary analysis method,with MR-Egger regression,weighted median(WM),sim-ple model,and weighted mode methods used as supplements,to analyze the causal association be-tween the counts of five types of white blood cells and VTE,followed by reverse MR analysis.RE-SULTS:Neutrophil and lymphocyte counts are caus-ally associated with the risk of VTE.For neutrophil count,the IVW estimate(OR=0.867,95%CI:0.761-0.981,P=0.031),MR-Egger estimate(OR=0.754,95%CI:0.571-0.996,P=0.048),weighted median es-timate(OR=0.846,95%CI:0.729-0.981,P=0.027),and weighted model estimate(OR=0.748,95%CI:0.595-0.942,P=0.014)were calculated.For lympho-cyte count,the IVW estimate(OR=0.838,95%CI:0.741-0.949,P=0.005)and weighted median esti-mate(OR=0.024,95%CI:0.718-0.977,P=0.024)were calculated.Reverse MR analysis showed a causal association between the risk of VTE and neu-trophil count,the IVW estimate(OR=0.989,95%CI:0.980-0.999,P=0.024).CONCLUSION:Neutrophil and lymphocyte counts are related to the risk of VTE,and decrease in neutrophil and lymphocyte numbers may increase the risk of VTE.VTE occur-rence risk is associated with neutrophil count,and reducing the risk of VTE occurrence may increase neutrophil count.Further research is needed to un-derstand the underlying biological mechanisms be-hind this relationship.

AIM:To explore the mechanism of BLJZF in the treatment of abnormal lipid metabo-lism based on network pharmacology,molecular docking andin vivo animal experiments.METHODS:TCMSP database,Swiss Target Prediction database,STITCH database and literature search were used to collect and query the chemical composition infor-mation of BLJZF and the corresponding target of drug chemical composition.Disease targets of lipid abnormalities were collected through GeneCards and OMIM databases.Metascape database was used to analyze the gene ontology function and the Kyoto Encyclopedia gene and genome pathway en-richment of common intersection targets.Cyto-scape software was used to construct the correla-tion network diagram of components and targets,so as to select major components and targets for molecular docking study.The hyperlipidemia model was induced by high fat diet,and the control group,model group,positive group and BLJZF group were set up.The serum lipid index contents of triglyceride(TG),total cholesterol(TC),low lipo-protein cholesterol(LDL-C)and high lipoprotein cholesterol(HDL-C)were detected after continuous administration for 4 weeks.The contents of oxida-tive stress index were detected:alanine amino-transferase(ALT)and aspartate aminotransferase(AST).The contents of superoxide dismutase(SOD)and malondialdehyde(MDA)were detected by ELI-SA.Hematoxylin-eosin(HE)staining was used to de-tect the pathological changes of liver tissue.RE-SULTS:A total of 25 components and 315 corre-sponding targets of BLJZF were obtained,1729 tar-gets of lipid abnormalities and 116 common tar-gets of BLJZF,among which the core targets were AKT1,TNF,IL1β,CASP3,etc.GO and KEGG enrich-ment analysis suggested that BLJZF may play a role through the lipid and atherosclerotic pathway,PI3K-Akt,AGE-RAGE in diabetic complications and other signaling pathways.Molecular docking showed that most of the core targets had high binding activity with the active ingredients.Animal experiments showed that compared with model group,TC,TG,LDL-C,ALT,AST and MDA in BLJZF group were sig-nificantly decreased,HDL-C and SOD were signifi-cantly increased,and the degree of liver fat defor-mation was reduced.CONCLUSION:BLJZF has a therapeutic effect on lipid abnormalities.It can treat lipid metabolism abnormalities through multi-component,multi-target and multi-pathway,and provide reference for subsequent drug research on BLJZF.