Objective To investigate the effect of electroacupuncture on nutritional obese mice through TLR5-gut microbio-ta pathway,and the underlying mechanism.Methods A total of 60 SPF C57BL/6 mice were selected.Among them,10 blank mice were assigned to normal group,and the nutritive obesity model was established in the other 50 mice,which was induced by high-fat diet.Twenty nutritive obesity model mice were screened and randomly divided into model group and electroacupuncture group,with 10 mice in each group.The electroacupuncture group was needled at Zhongwan,Tianshu,Guanyuan and Fenglong points.And after obtaining Qi,electroacupuncture treatment was conducted on those mice for 21 days continuously.The change in differences of general indexes(body weight,Lee's index),tissue indexes(perirenal adipose-tissue mass),serum indexes[cho-lesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-C),low-density lipoprotein(LDL-C),blood glucose),molecular indexes[leptin(LEP),adiponectin(ADPN),interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),lipopo-lysaccharide-binding protein(LBP)and cholecystokinin(CCK)]were observed.TLR5 protein distribution was detected by immu-nohistochemical reaction,and TLR5 gene expression was detected by RT-PCR.Structural differences of intestinal flora was ana-lyzed by second generation 16S rDNA gene sequencing technology.Results The body weight,Lee's index,fat mass around kid-ney,serum contents of CHO,TG,HDL-C,the contents of LEP and FFA in fat tissue,and contents of IL-6,IL-1β,TNF-α,LBP in intestinal mucosa tissue of model group were significantly higher than that of the normal group,and the content of adipocyto-kine ADP was significantly lower.After electroacupuncture treatment,those indicators were significantly improved.The protein distribution and gene expression of TLR5 in the intestinal mucosa of the model group were significantly higher than those of the normal group,and were significantly down-regulated after electroacupuncture intervention.The number of intestinal flora spe-cies in the model group was significantly lower than those in the normal group,and were significantly increased after electroacu-puncture intervention.Proportions of Bacteroidia,Gammaproteobacteria,Eggerthellacrae and Sutterellaceae were significantly increased,while proportions of Bacilli,Clostridia,Clostridiaceae and Actinobacteria were significantly decreased.Changes in gut flora were significantly reversed after electroacupuncture intervention.Conclusion Electroacupuncture has a satisfying effect in treatment of nutritional obesity.It can regulate the distribution and expression of TLR5 protein in intestinal mucosa by balancing the structure of intestinal flora,reduce the chronic inflammatory reaction of intestinal mucosa,promote lipid metabo-lism of the body,and achieve the purpose of weight loss and lipid reduction.

OBJECTIVE: To investigate the therapeutic mechanism of resveratrol (RES) for Alzheimer's disease (AD) in light of network pharmacology. METHODS: We searched PubChem, BATMAN-TCM, Genecards, AD, TTD, String 11.0, AlzData, SwissTargetPrediction, Metascape and other databases for the therapeutic targets of RES and human AD-related targets. The intersection was determined using Venny 2.1 to obtain the therapeutic targets of RES for AD. The protein-protein interaction (PPI) network was constructed, the gene ontology (GO) was enriched and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) were analyzed. Cytoscape 3.7.1 software was used to construct a target-signaling pathway network of RES in the treatment of AD. Molecular docking verification was carried out on SwissDock (http://www.swissdock.ch/docking). We examined a 293Tau cell model of AD for changes in protein levels of pS396, pS199, Tau5, CDK5, glycogen synthase kinase 3β (GSK3β) and p-GSK3β in response to RES treatment using Western blotting. RESULTS: We obtained 182 targets of RES, 525 targets related to AD, and 36 targets of RES for AD treatment, among which 34.6% of the targets were protein-modifying enzymes, 27.7% were metabolite invertase, 13.8% were gene-specific transcriptional regulators, and 10.3% were transporters. The core key targets of RES in the treatment of AD included INS, APP, ESR1, MMP9, IGF1R, CACNA1C, MAPT (microtubule- associated protein Tau), MMP2, TGFB1 and GSK3B. Enrichment analysis of GO biological process suggested that the biological function of RES in AD treatment mainly involved the response to β-amyloid protein, positive regulation of transferase activity, the transmembrane receptor protein tyrosine kinase signaling pathway, regulation of behavior, learning or memory, aging, and transmembrane transport. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathways were AD pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and MAPK signaling pathway. Molecular docking results showed that RES had strong binding with ESR1, GSK3B, MMP9, IGF1R, APP and INS. In the cell model of AD, treatment with 50 μmol/L RES for 12 h significantly reduced the levels of pS396 and pS199 by regulating CDK5 and GSK3β activity ( CONCLUSIONS RES produces therapeutic effects on AD by acting on multiple targets and affecting multiple signaling pathways and improves AD-associated pathologies
Alzheimer Disease/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Resveratrol/pharmacology*

BACKGROUNDA positive association between the ABO blood types and survival has been suggested in several malignancies. The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer (NSCLC).

METHODSWe retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1, 2005 and December 31, 2009. The relationship between the ABO blood types and survival was investigated. In addition, univariate and multivariate analyses were performed.

RESULTSGroup 1 (patients with the blood type O or B) had significantly prolonged overall survival (OS) compared with group 2 (patients with the blood type A or AB), with a median OS of 74.9 months versus 61.5 months [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.72-0.96; P = 0.015]. Additionally, group 1 had significantly longer disease-free survival (DFS; HR 0.86; 95% CI 0.76-0.98; P = 0.022) and locoregional relapse-free survival (LRFS; HR 0.79; 95% CI 0.64-0.98; P = 0.024) than group 2. The association was not significantly modified by other risk factors for NSCLC, including smoking status, pathologic tumor-node-metastasis stage, pT category, pN category, and chemotherapy.

CONCLUSIONSThere is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC. Patients with the blood type O or B had significantly prolonged OS, DFS, and LRFS compared with those with the blood type A or AB.

ABO Blood-Group System ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; Disease-Free Survival ; Humans ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies ; Risk Factors