Objective To explore the shared mechanisms of genes related to three common chronic diseases non-alcoholic fatty liver disease(NAFLD),type 2 diabetes mellitus(T2DM)and atherosclerosis(AS)with ageing as well as potential therapeutic agents by using bioinformatics analysis,machine learning algorithms and molecular docking methods and techniques.Methods Ageing-related genes were collected and organized from AgeingAtlas,CellAge,GenAge,and MSigDB databases.After taking the intersection of genes related to NAFLD,T2DM and AS obtained from databases such as CTD,DisGeNET,GeneCards,OMIM,PharmGKB,and TTD and the gene sets obtained based on the GEO differential gene analysis,we obtained the set of related disease genes for these three common chronic diseases.The KEGG pathway enrichment analysis was performed on the ageing gene set and the three disease-related gene sets using the clusterProfiler package,and the intersection was taken.The enriched genes in the KEGG pathway were merged and imported into the STRING database;the PPI network was constructed.We analyzed the core sub-modules in the PPI network using the MCODE tool and calculated the essential values of Nim and Cim for each node and module.Meanwhile,three machine learning models were used to screen the feature genes:the Lasso regression model,the Boruta algorithm,and the random forest model.The HIT2.0 database was utilized to find the targeted TCM small molecules related to the key feature genes.Small molecules were evaluated and analyzed by ADMET using SwissADME and ADMETlab 3.0 online system.The molecular docking method was utilized to dock the key action targets and screen small molecules.Results A total of 1 325,616,78,and 597 genes related to ageing,NAFLD,T2DM,and AS were obtained.The KEGG pathway enrichment analysis results for ageing and the three diseases were taken to intersect to get two shared intersecting pathways containing 243 genes.The PPI network was constructed,and Cluster 2 had the highest Cim value among the three core submodules.According to the results of signature gene screening,combined with PPI network module analysis results,four signature genes related to ageing were found:CDK6,CDKN1A,MYC,and PTEN.These four targets have 94 potential TCM small molecule candidates,among which resveratrol(RSV)is a TCM small molecule common to these four targets.The ADMET evaluation showed that it had good drug-forming properties.The PTEN target had a high Nim value,and molecular docking of RSV with PTEN showed good binding stability.Conclusion A potential herbal small molecule,RSV,was identified from the perspective of ageing,which may prevent and treat three common chronic diseases,namely,NAFLD,T2DM and AS,by regulating the key gene PTEN.

AIM:This study aimed to investigate the mechanisms by which treadmill exercise ameliorates de-pressive-like behaviors and hippocampal neuronal damage in chronic restraint stress(CRS)mice by regulating mitophagy via the Sirt1/PGC-1α signaling axis.METHODS:Forty C57BL/6J mice were randomly assigned to control,CRS,CRS+exercise(EXE)and EXE groups(n=10).The mice in CRS and CRS+EXE groups underwent 4 h of daily restraint for 28 consecutive days to establish a depression model.The mice in CRS+EXE and EXE groups received 8 weeks of treadmill training(6 sessions per week).Depressive-like behaviors were evaluated using the open field test,sucrose preference test,and tail suspension test.Hippocampal neuronal morphology and pathological changes were examined using hematoxy-lin-eosin and Nissl staining,while neuronal apoptosis was assessed through TUNEL staining.Mitochondrial ultrastructure was examined via transmission electron microscopy.Mitochondrial membrane potential and ATP content were measured using JC-1 assay and ATP assay kits,respectively.The expression levels of silent information regulator 1(Sirt1),peroxi-some proliferator-activated receptor γ coactivator-1α(PGC-1α),PTEN-induced kinase 1(PINK1)and parkin were as-sessed at both mRNA and protein levels by RT-qPCR and Western blot assays,as well as key markers of mitophagy[mi-crotubule-associated protein 1 light chain 3(LC3)and P62]and apoptosis(cleaved caspase-9 and cleaved caspase-3).RESULTS:Compared with control group,CRS mice exhibited significantly reduced central zone entries and time(P<0.01),decreased sucrose preference(P<0.01),increased immobility time(P<0.01),severe hippocampal neuronal damage,elevated apoptosis rate(P<0.01),mitochondrial deterioration;reduced membrane potential and ATP content(P<0.01),decreased mRNA expressions of Sirt1,PGC-1α,PINK1,and parkin(P<0.01),reduced protein levels of Sirt1,PGC-1α,PINK1,parkin and LC3(P<0.01),and increased expression of P62,cleaved caspase-9,and cleaved caspase-3(P<0.01).The mice in CRS+EXE group showed significant improvements in all these parameters compared to CRS group(P<0.05 or P<0.01).CONCLUSION:Treadmill exercise mitigates CRS-induced depressive-like behaviors,mi-tochondrial dysfunction,and neuronal apoptosis in mice by activating the hippocampal Sirt1/PGC-1α/mitophagy axis.

AIM:This study aimed to investigate the mechanisms by which treadmill exercise ameliorates de-pressive-like behaviors and hippocampal neuronal damage in chronic restraint stress(CRS)mice by regulating mitophagy via the Sirt1/PGC-1α signaling axis.METHODS:Forty C57BL/6J mice were randomly assigned to control,CRS,CRS+exercise(EXE)and EXE groups(n=10).The mice in CRS and CRS+EXE groups underwent 4 h of daily restraint for 28 consecutive days to establish a depression model.The mice in CRS+EXE and EXE groups received 8 weeks of treadmill training(6 sessions per week).Depressive-like behaviors were evaluated using the open field test,sucrose preference test,and tail suspension test.Hippocampal neuronal morphology and pathological changes were examined using hematoxy-lin-eosin and Nissl staining,while neuronal apoptosis was assessed through TUNEL staining.Mitochondrial ultrastructure was examined via transmission electron microscopy.Mitochondrial membrane potential and ATP content were measured using JC-1 assay and ATP assay kits,respectively.The expression levels of silent information regulator 1(Sirt1),peroxi-some proliferator-activated receptor γ coactivator-1α(PGC-1α),PTEN-induced kinase 1(PINK1)and parkin were as-sessed at both mRNA and protein levels by RT-qPCR and Western blot assays,as well as key markers of mitophagy[mi-crotubule-associated protein 1 light chain 3(LC3)and P62]and apoptosis(cleaved caspase-9 and cleaved caspase-3).RESULTS:Compared with control group,CRS mice exhibited significantly reduced central zone entries and time(P<0.01),decreased sucrose preference(P<0.01),increased immobility time(P<0.01),severe hippocampal neuronal damage,elevated apoptosis rate(P<0.01),mitochondrial deterioration;reduced membrane potential and ATP content(P<0.01),decreased mRNA expressions of Sirt1,PGC-1α,PINK1,and parkin(P<0.01),reduced protein levels of Sirt1,PGC-1α,PINK1,parkin and LC3(P<0.01),and increased expression of P62,cleaved caspase-9,and cleaved caspase-3(P<0.01).The mice in CRS+EXE group showed significant improvements in all these parameters compared to CRS group(P<0.05 or P<0.01).CONCLUSION:Treadmill exercise mitigates CRS-induced depressive-like behaviors,mi-tochondrial dysfunction,and neuronal apoptosis in mice by activating the hippocampal Sirt1/PGC-1α/mitophagy axis.

Objective To explore the shared mechanisms of genes related to three common chronic diseases non-alcoholic fatty liver disease(NAFLD),type 2 diabetes mellitus(T2DM)and atherosclerosis(AS)with ageing as well as potential therapeutic agents by using bioinformatics analysis,machine learning algorithms and molecular docking methods and techniques.Methods Ageing-related genes were collected and organized from AgeingAtlas,CellAge,GenAge,and MSigDB databases.After taking the intersection of genes related to NAFLD,T2DM and AS obtained from databases such as CTD,DisGeNET,GeneCards,OMIM,PharmGKB,and TTD and the gene sets obtained based on the GEO differential gene analysis,we obtained the set of related disease genes for these three common chronic diseases.The KEGG pathway enrichment analysis was performed on the ageing gene set and the three disease-related gene sets using the clusterProfiler package,and the intersection was taken.The enriched genes in the KEGG pathway were merged and imported into the STRING database;the PPI network was constructed.We analyzed the core sub-modules in the PPI network using the MCODE tool and calculated the essential values of Nim and Cim for each node and module.Meanwhile,three machine learning models were used to screen the feature genes:the Lasso regression model,the Boruta algorithm,and the random forest model.The HIT2.0 database was utilized to find the targeted TCM small molecules related to the key feature genes.Small molecules were evaluated and analyzed by ADMET using SwissADME and ADMETlab 3.0 online system.The molecular docking method was utilized to dock the key action targets and screen small molecules.Results A total of 1 325,616,78,and 597 genes related to ageing,NAFLD,T2DM,and AS were obtained.The KEGG pathway enrichment analysis results for ageing and the three diseases were taken to intersect to get two shared intersecting pathways containing 243 genes.The PPI network was constructed,and Cluster 2 had the highest Cim value among the three core submodules.According to the results of signature gene screening,combined with PPI network module analysis results,four signature genes related to ageing were found:CDK6,CDKN1A,MYC,and PTEN.These four targets have 94 potential TCM small molecule candidates,among which resveratrol(RSV)is a TCM small molecule common to these four targets.The ADMET evaluation showed that it had good drug-forming properties.The PTEN target had a high Nim value,and molecular docking of RSV with PTEN showed good binding stability.Conclusion A potential herbal small molecule,RSV,was identified from the perspective of ageing,which may prevent and treat three common chronic diseases,namely,NAFLD,T2DM and AS,by regulating the key gene PTEN.

In order to solve the problems in traditional health management experimental teaching, such as high cost, safety and difficult repeatability, a virtual simulation experimental teaching platform for health management combined with Traditional Chinese Medicine (TCM) characteristics has been constructed by using virtual simulation, multimedia, and human-computer interaction technologies, which comprises TCM constitution identification, TCM health management and health management service process. Through the combination of virtual simulation and reality situation, the platform has formed an online and offline model of experimental teaching, which has improved the innovation and practice ability of students and enhanced the teaching quality.

Objective:To explore the design of an evaluation index system with feasibility and appropriateness, and to conduct cloud model evaluation, in order to provide reference for the high-quality development of public traditional Chinese medicine(TCM) medical institutions in China.Methods:The Delphi method and analytic hierarchy process were used to construct an evaluation index system for public TCM medical institutions and calculate the index weights. Then the cloud model theory was applied to comprehensively evaluate the index system.Results:The index system of TCM medical institutions including 5 primary indicators and 12 secondary indicators of " external governance" module and 9 primary indicators and 62 secondary indicators of " internal management" module was constructed. The cloud model of the index system was(4.608, 1.022, 0.151), and the cloud rank was in the range of " very good" .Conclusions:The indicator system constructed in this study is relatively objective, scientific, and reasonable. While ensuring the accuracy and credibility of the evaluation results, it also adds evaluation information, which has certain guiding significance for promoting the high-quality development of public TCM medical institutions.

The protective effect and mechanism of Oroxylin A, a naturally occurring compound in Scutellaria baicalensis Georgi, was investigated in this study. Isoproterenol administration to rats triggered classic cardiac failure, as demonstrated by objective parameters of cardiac dysfunction. Intragastric administration of oroxylin A at the dose of 25, 50 and 100 mg/(kg·d)significantly improved deranged cardiac parameters in the isoproterenol-induced heart failure model in a dose-dependent manner. At the same time, oroxylin A markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine, aldosterone, brain natriuretic peptide, endothelin 1, angiotensin II and so on. Mechanistically, augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by oroxylin A. Taken together, these results suggest that oroxylin A ameliorates heart failure through promoting autophagy in myocardial cells.

Objective To investigate clinical effect and mechanism of Yudanrongxin pills in the treatment of patients with acute myocardial infarction ( AMI) .Methods 86 cases of AMI in our hospital from February 2014 to February 2015 were selected and divided into the observation group and the control group, with 43 cases in each group.The patients in the control group were treated with conventional therapy, while patients in observation group were treated with Yudanrongxin pills on the basis of the control group.The related inflammation factors, indicators of myocardial injury and heart function index were compared between two groups before and after treatment.Results Compared with before treatment, in both two groups after treatment, the serum inflammatory factors including high-sensitivity C-reactive protein(hs-CRP), IL-6,soluble vascular cellular adhesion molecule-1 (sVCAM-1), TNF-αand P-selectin decreased, the myocardial injury criterion including creatine kinase-MB (CK-MB), lactate dehydrogenase (LD), myocardial troponin I (cTnI) and myoglobin (Mb) decreased,the cardiac function indexes of left ventricular end systolic volume (LVESV) and left ventricular end diastolic volume (LVEDV) decreased and left ventricular ejection fraction (LVEF) increased (P<0.05).Compared with control group, the hs-CRP,IL-6,sVCAM-1,TNF-α,P-selectin,CK-MB,LD,cTnI and Mb in observation group were lower(P<0.05).The degree of improvement at cardiac function was better than that in control group (P<0.05).Conclusion Yudanrongxin pills could better improve cardiac function in treatment with AMI, its role was relative to inhibition of inflammatory factors and myocardial protection against injury.

Objective To investigate the effect and mechanism of Yiqi Shuxin pills in the treatment with viral myocarditis(VMC).Methods 56 cases of VMC in our hospital were randomly divided into the experimental group and the control group,28 cases in each group.The patients in the control group were with routine treatment,and these in the experimental group were treated with Yiqi Shuxin pills based on the control group.The clinical effects between the two groups were compared, and the changes of miR, myocardial enzyme spectrum and immunity were compared before and after treatment.Results The total effective rate was 92.86% in the experimental group and was 72.57% in the control group,there was statistical significance between the two groups(P<0.05);There was no significant difference between the two groups before treatment at miR-1,miR-133,miR-21,CK-MB, cTnI,LDH,CD3 +,CD4 +,CD8 +,NK in serum;The content of miR-1,miR-133,CD3 +,CD4 +,CD8 +,NK after treatment in the two groups were higher than before treatment(P <0.05),miR-21,CK-MB,cTnI and LDH were lower than before(P <0.05);The improvement of these indicators in the experimental group was superior to that in the control group(P<0.05).Conclusion Yiqi Shuxin pills could improve the therapeutic effect of VMC,the mechanism maybe related to improving the circulation of blood miR and enhance cellular immune function.

OBJECTIVETo prepare sodium alginate-nanohydroxyapatite composite material and to explore its feasibility as a bone repair material.

METHODSSodium alginate-nanohydroxyapatite composite material was prepared using chemical cross-linking and freeze-drying technology. The composite was characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM) and its porosity was measured by liquid displacement method. The fifth passage of bone marrow stromal stem cells (BMSCs) were incubated on the composite material and then growth was observed by inverted microscope and SEM. BMSCs were cultured with liquid extracts of the material, methyl thiazolyl tetrazolium (MTT) assay was used to calculate the relative growth rate (RGR) on 1, 3, 5 d and to evaluate the cytotoxicity. Fresh dog blood was added into the liquid extracts to conduct hemolysis test, the spectrophotometer was used to determine the optical density (OD) and to calculate the hemolysis rate.

RESULTSSodium alginate-nanohydroxyapatite composite material displayed porosity, the porous pore rate was (88.6 +/- 4.5)%. BMSCs showed full stretching and vigorous growth under inverted microscope and SEM. BMSCs cultured with liquid extracts of the material had good activities. The toxicity of composite material was graded as 1. Hemolysis test results showed that the hemolysis rate of the composite material was 1.28%, thus meeting the requirement of medical biomaterials.

CONCLUSIONThe composite material fabricated in this study has high porosity and good biocompatibility.

Alginates ; Biocompatible Materials ; Cells, Cultured ; Glucuronic Acid ; Hexuronic Acids ; Humans ; Mesenchymal Stromal Cells ; Porosity ; Tissue Engineering ; Tissue Scaffolds