During the progression of heart failure(HF),abnormal transduction of the transforming growth factor-β(TGF-β)/Smads signaling pathway is important mechanism of myocardial fibrosis(MF)in HF.TGF-β,a key factor in MF,is in an overexpression state in the process of MF in HF,and Smads is a major effector downstream of TGF-β.The TGF-β/Smads pathway induces abnormal proliferation of myofibroblasts,aggravates myocardial extracellular matrix deposition,and reduces the ability of the cardiac tissues to resist fibrosis,which plays a complex role in the pathogenesis of MF in HF.Traditional Chinese medicine(TCM)has the efficacy of unequivocal inhibiting myocardial collagen deposition,anti-MF,protecting the myocardium and improving cardiac function in the prevention and treatment of MF in HF and so on,and the TGF-β/Smads pathway is one of the key pathways through which TCM monomers,TCM combinations,and proprietary medicines can exert their cardioprotective effects on the HF.This paper reviews the existing experimental research results of TCM intervening in the TGF-β/Smads pathway for the treatment of MF in HF over the past 10 years,with a view to providing theoretical basis for the prevention and treatment of HF MF well as the development and of new drugs.

Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)％,(6.28±0.20)％,(24.96±1.18)％,(12.36±0.49)％,(18.76±0.68)％and(4.59±0.26)％;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P＜0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.

Objective To investigate the effects of liver-specific knockout of adenosine 5'-monophosphate-activated protein kinase α(AMPKα)on pancreatic function and glucose metabolism-related genes in mice.Methods AMPKα1/α2flox/flox mice were divided into blank group(common feed)and model group(60％high fat choline deficiency feet)with eight mice in each group,and another 8 AMPKα1/α2flox/flox/Alb-Cre+mice were divided into the knockout group(60％high fat choline deficiency feet).The kit detected the levels of blood lipids and liver function indexes.The differential genes in the mouse pancreas were detected by transcriptome sequencing.The expression of differential genes in mice was detected by real-time fluorescence quantitative polymerase chain reaction and Western blotting.Results The levels of triglyceride in the blank group,model group and knockout group were(0.94±0.11),(0.71±0.14)and(1.05±0.17)mmol·L-1;the levels of triglyceride and high-density lipoprotein were(1.62±0.07),(0.44±0.08)and(0.90±0.06)mmol·L-1;the levels of glutamic oxaloacetic transaminase were(7.02±5.87),(15.60±3.15)and(22.70±2.14)U·L-1;the levels of glutamic pyruvic transaminase were(14.56±11.55),(48.64±15.84)and(75.40±11.96)U·L-1;the expression levels of phosphoenolpyruvate carboxykinase 1(PCK1)mRNA were 1.00±0,1.37±0.25 and 0.31±0.18;the relative expression levels of PCK1 protein were 0.77±0.27,1.23±0.43 and 0.51±0.40,respectively.Significant differences existed in the above indexes between the knockout group and the model group(all P＜0.05).Conclusion PCK1 gene may be an essential gene mediating the effect of liver AMPKα on islet function.

Objective To observe the protective effects of codonopsis pilosulae polysaccharide on lung tissues in mice with acute lung injury(ALI)induced by lipopolysaccharide(LPS)and its mechanism.Methods Fifty male Kunming mice were randomly divided into control group,model group,dexamethasone group,codonopsis polysaccharide high-dose group(300 mg/kg)and codonopsis polysaccharide low-dose group(150 mg/kg).The ALI model was established by intraperitoneal injection of LPS.All mice were given gavage administration according to the grouping except for the control group.0.3 s force expiratory volume(FEV 0.3)and force spirometry(FVC)and their ratios were measured using multiparametric lung function test system.The histopathology change of mouse lung was detected by hematoxylin-eosin(HE)staining,and the classification and count of inflammatory cells in alveolar lavage fluid(BALF)was detected by Richter-Giemsa staining.Levels of IL-1β,IL-6,MPO and TNF-α were measured by ELISA in BALF,and Western blot was used to detect the protein expression level of p-p38,p-IκB-α and p-p65.Results Compared with those in the control group,lung histopathological damage was more pronounced in the model mice,with significantly lower FEV 0.3,FVC,FEV0.3/FVC assay value,but signifi-cantly higher lung tissue wet mass/dry mass(W/D),neutrophils,lymphocytes,IL-1β,IL-6,MPO,TNF-α,p-p38 MAPK,p-IκB-α,and p-p65(P<0.05);while codonopsis pilosulae polysaccharide could significantly reverse these effects.Conclusion Codonopsis pilosulae polysaccharide plays a protective role against LPS-induced ALI via inhibiting MAPK/NF-κB pathway to reduce the pathological damage of lung tissue,and the level of inflammatory factors,thus to improve lung function in ALI model mice.

Cordycepin (Cpn), a natural active compound derived from the traditional Chinese medicine Cordyceps sinensis, has antifibrotic, antioxidant, and anti-inflammatory effects, but the impact of Cpn on pulmonary fibrosis and the downstream molecular mechanism remain unclear. In this study, A549 cells were induced by transforming growth factor β1 (TGFβ1) in vitro, the viability of A549 cells was evaluated by CCK-8 assay; and migration of A549 cells were detected by wound healing assay, invasion of A549 cells were detected by transwell assay. Molecular docking and molecular dynamics simulations were used to predict the interaction of histone deacetylase 7 (HDAC7) with vimentin and the association of Cpn with HDAC7. The pulmonary fibrosis model of mice was established by bleomycin in vivo to investigate the effect of Cpn on pathological changes of lung tissue. The impact of Cpn and molecular mechanism on pulmonary fibrosis were studied by Western blot assay, cell transfection assay, immunoprecipitation assay, immunofluorescence assay, immunohistochemistry and real-time quantitative PCR (RT-qPCR). All animal experiments were approved by the Shanghai Children's Medical Center Experimental Animal Ethics Committee (grant No. SCMC-LAWEC-2022-017). Results showed that Cpn had no toxic effect on A549 cells even at the concentration of 100 μmol·L^-1. Cpn inhibited migration and invasion of A549 cells and reduced deposition of collagen, the degree of lung inflammation and fibrosis in mice; in vivo and in vitro models, Cpn significantly reversed mRNA and protein expressions of epithelial-mesenchymal transition (EMT) and lung fibrosis markers collagen I, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and E-cadherin and HDAC7. Deficiency of HDAC7 suppressed TGFβ1-induced EMT and expression of collagen I; vimentin interacted with HDAC7; and molecular docking experiment revealed that Cpn was interrelated with HDAC7. In conclusion, Cpn can target HDAC7 to mediate EMT and exert its anti-fibrotic effect, the inhibition of EMT and the improvement of pulmonary fibrosis provide a new idea and choice for the development of anti-pulmonary fibrosis drug.

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL^-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L^-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.

Objective To investigate the therapeutic effect and mechanism of Jianwei Xiaozhang Tablets on rats with precancerous lesions of gastric cancer(PLGC).Methods Forty male SD rats were randomly divided into the normal group,the model group,the folic acid group and the Jianwei Xiaozhang Tablets group,with 10 rats in each group.In addition to the normal group,the other three groups of rats were prepared by gavage with Ranitidine Aqueous Solution combined with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)solution drinking method for the preparation of PLGC model.After successful modeling,drugs were administered accordingly for 7 weeks.The changes in body mass of rats during modeling and drug administration were recorded,the gross view of the stomach was observed and scored pathologically,the coefficients of spleen and liver were determined,the pathological changes in gastric tissue were observed by hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA)was used to measure serum gastrin(GAS),motilin(MTL)and glucagon(GC),Alisin Blue-Periodic Acid Schiff's(AB-PAS)staining was used to observe the thickness of the mucosal layer of gastric tissues,the expressions of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),and endothelial-type nitric oxide synthase(eNOS)proteins in gastric tissues were detected by protein immunoblotting(Western Blot),and the expression of vascular endothelial growth factor A(VEGFA)protein in gastric tissues was detected by immunofluorescence staining.Results Compared with the normal group,the body mass of rats in the model group grew slowly during the experimental period,gastric macroscopic pathological scores were significantly increased(P＜0.01),splenic coefficient and hepatic coefficient were significantly decreased(P＜0.01),the gastric tissues showed cuprocyte hyperplasia and intestinal chemotaxis,gastric tissues'inflammation scores were significantly increased(P＜0.01),the serum GAS content was significantly increased(P＜0.01),and the MTL,GC contents were significantly reduced(P＜0.05),and the thickness of the mucous membrane layer of gastric tissue was significantly reduced(P＜0.05),the protein expression levels of PI3K,p-PI3K,Akt,p-Akt and eNOS were reduced(P＜0.01),and the protein expression level of VEGFA was reduced(P＜0.01);compared with the model group,the above indexes of the Jianwei Xiaozhang Tablets group and the folic acid group were all significantly improved(P＜0.05 or P＜0.01),among which,the Jianwei Xiaozhang Tablets group had a better improvement effect in the proliferation of cup cells and intestinal chemotaxis in gastric tissues,the content of serum GAS,and the thickness of the mucous layer in gastric tissues.Conclusion The mechanism of the improvement of PLGC in rats by Jianwei Xiaozhang Tablets may be related to the activation of the PI3K-Akt-eNOS pathway,which in turn promotes the angiogenesis and repair of gastric damaged tissues.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.