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OBJECTIVE To identify the chemical components of Changtong oral liquid （CTOL），and to provide reference for the basic research and secondary development of its pharmacological substances. METHODS UHPLC-Orbitrap HRMS technique was adopted. CTOL sample was separated on a Hypersil Gold column with mobile phase consisted of 0.1% formic acid （containing 5 mmol/L ammonium formate）-acetonitrile （gradient elution）. The eluent was detected in positive and negative ion modes using an electrospray ionization source. The data was processed by Xcalibur 4.3 and Compound Discoverer 3.3 software. The primary and secondary mass spectra data of each compound were collected. The unknown compounds were identified according to the mass spectrometry library of the instrument and the network databases mzCloud，mzVault，etc. Through matching with the pharmacology database and analysis platform of the traditional Chinese medicine system，the chemical components could be attributed to the traditional Chinese medicine. RESULTS Fifty-three chemical components were identified and analyzed from CTOL，such as 24 flavonoids，8 quinones，5 phenylpropanoids，4 sugars and glycosides，5 organic acids，3 amino acids，1 alkaloid，1 phenolic and 2 other compounds. Among them，12 components were derived from Salvia miltiorrhiza，9 from Citrus aurantium，7 from Rheum palmatum，4 from Angelica sinensis，1 from Magnolia officinalis，16 from Glycyrrhiza uralensis，and 4 from many kinds of medicinal materials. CONCLUSIONS CTOL mainly contains flavonoids，quinones and phenylpropanoid compounds，and its chemical components mainly come from G. uralensis，S. miltiorrhiza and C. aurantium.
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Objective:To observe the effects of sacubitril/valsartan (LCZ696) on viral replication and cardiomyocyte apoptosis in mice with coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) and to analyze the underlying mechanisms.Methods:Forty BALB/c mice were randomly divided into four groups with 10 in each group: Sham, Sham+ LCZ696, VMC, and VMC+ LCZ696 groups. VMC model was established by intraperitoneal injection of 0.1 ml of CVB3 with a concentration of 10 6 TCID 50/ml into BALB/c mice, while the sham intervention was an equal volume of saline. The day of virus injection was defined as day 0. LCZ696 was administered by gavage at a dose of 60 mg/kg every day for seven consecutive days starting from day 1. Mouse survival rates were calculated. Echocardiography was used to evaluate the cardiac function of mice. The level of creatine kinase-MB (CK-MB) was detected by ELISA. Western blot was used to detect the levels of inflammatory cytokines (IL-6, TNF-α), apoptosis-related proteins (caspase-3, cleaved-caspase-3, Bax, Bcl-2), CVB3 surface protein (VP-1) and p-AKT/AKT in the hearts of mice. CVB3 mRNA in mouse hearts was measured by PCR. Inflammatory cell infiltration and cell apoptosis in mouse hearts were observed by HE staining and TUNEL staining, respectively. Results:Compared with the Sham group, the mice in the VMC group had a decreased survival rate and impaired cardiac function ( P<0.05). The levels of CK-MB, IL-6, TNF-α, cleaved-caspase-3/caspase-3, Bax/Bcl-2, VP-1, and CVB3 mRNA in the hearts of VMC mice increased significantly ( P<0.05), accompanied by increased expression of AKT, decreased phosphorylation of AKT ( P<0.05) and increased cell apoptosis. LCZ696 reversed the above changes. It could increase the survival rate, improve the cardiac function ( P<0.05), decrease cardiac inflammation, cell apoptosis and viral replication ( P<0.05), and increase the phosphorylation of AKT ( P<0.05). LCZ696 had no significant effects on the survival rate, cardiac function, myocardial injury, cardiac inflammation, cell apoptosis, viral replication or the expression of PI3K/AKT signaling pathway-related proteins in normal mice. Conclusions:LCZ696 could significantly inhibit cardiomyocyte apoptosis and reduce CVB3 replication in the hearts of VMC mice by regulating the PI3K/AKT pathway, thereby improving mouse cardiac function and survival rate.
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OBJECTIVE：To investigate the potential mechanism of Salvia miltiorrhiza in the treatment of postoperative abdominal adhesion （PAA）. METHODS ：Active components and target genes of S. miltiorrhiza were retrieved from TCMSP database，SwissADME database ，Perl database ，UniProt database and other databases. GeneCards ，OMIM and PubMed database were used to retrieve target genes related to PAA. Venn diagram was drawn by using mapping tool of bioinformatic online database so as to screen the intersecting targets of active component-PAA. STRING platform was adopted to establish target network related to active component-PAA and protein-protein interaction （PPI）network of intersecting targets ，etc.，and to screen hub genes. Gene ontology（GO）and Kyoto Encyclopedia of Genes and Genom es（KEGG）pathway enrichment were carried out by using R 3.6.1 software. Using the protein encoded by hub gene as receptor and tanshinone Ⅱ A as ligand ，the molecular docking was carried out with AutoDock 1.5.6 tool. RESULTS ：A total of 38 active components of S. miltiorrhiza with high gastrointestinal absorption and their corresponding 72 targets，755 PAA-related target genes were identified. Results of Venn diagram showed that there were 33 intersecting targets of active components of chuqi90@163.com S. miltiorrhiza with PAA. Tanshinone ⅡA，dihydrotanshinolac- tone and other components may be important nodes of the target network related to active component-PAA. FOS，APP，ACHE， CASP3 and PTGS2 may be the hub genes in PPI network of intersecting targets. Results of GO enrichment showed that the intersecting targets were mainly concentrated in adrenergic receptor activity ，catecholamine binding ，G protein-coupled amine receptor activity and so on ；KEGG pathway enrichment analysis showed that the intersecting targets were mainly enriched in neuroactive ligand-receptor interaction ，cGMP-PKG signaling pathway ，endocrine resistance ，EGFR-tyrosine kinase inhibitor resistance and calcium signaling pathway.Molecular docking analysis showed that tanshinone ⅡA could form hydrogen bonds with many amino acid residues such as VAL- 580 of proto oncogenes c-Fos ，amyloid precursor protein ，acetylcholinesterase，caspase 3 and prostaglandin G/H synthase 2. CONCLUSIONS ：The active components of S. miltiorrhiza play a role in the treatment of PAA by directly or indirectly acting on neuroactive ligand-receptor interaction ，cGMP-PKG signaling pathway ，endocrine resistance ， EGFR-tyrosine kinase inhibitor resistance resistance and calcium signaling pathway.
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Objective To evaluate the relationship of serum thrombospondin?1(TSP?1)with the micro?inflammation in maintenance hemodialysis(MHD),and to explore its clinical prognosis value in the MHD patients. Methods A total of 84 MHD patients in our hospital were enrolled and prospectively followed for 2 years. The serum levels of TSP?1 and clinical inflammatory markers were detected. Patients were divided into groups according to different serum TSP?1 levels. The clinical inflammatory markers were detected by using ELISA analysis. Pearson simple correlation analysis method was applied to analyze the correlation between TSP?1 levels and inflammation related indicators. At the same time the prognosis and turnover of MHD patients was analyzed by using Kaplan Meier survival curve and survival rate was compared by Deleted:compared log?rank test. Cox regression analysis was used to calculate the hazard ratio (HR) and Deleted:using 95% confidence interval (CI). Results The indexes of blood lipid and inflammatory factors in the TSP?1 high?level groups were higher than that in TSP?1 low?level groups (P<0.05). Correlation analysis showed that the serum TSP?1 level was positively correlated with the serum lipid and inflammatory factors. Survival curve analysis showed that the mortality rate of TSP?1 high?level group was higher than that of TSP?1 low?level groups. Cox hazards analysis revealed that the patients with high?level TSP?1 had a higher risk for mortality than these TSP?1 low?level patients. This predictive value still existed after multivariate adjustment for age,blood lipid,serum albumin and other factors (P < 0.001). Conclusion The serum TSP?1 levels were associated with micro?inflammation and had a significant value in predicating the prognosis of MHD patients.
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Objective To investigate the effect of delighted thinking on improving negative emotion of depression patients. Methods 100 depression patients were randomly divided into the observation group and the control group with 50 in each according to admission sequence. Both groups was executed antidepressionant drugs treatment and routine psychiatric care simultaneously. The observation group was given delighted thinking training on the basis of above treatment. The emotional recovery of two groups was observed. Results There was significant difference on facial expression, communication and limbs language after executing delighted thinking training in the observation group. And there was significant difference on scores of Hamilton depression rating scale (HAMD) at discharge. Scores of Nurses' Observation Scale during early, middle and late stage of delighted thinking training greatly improved compared with those before training. Conclusions Delighted thinking contributes to throw off negative thinking pattern of self-denial, stimulate positive passion threshold, improve depressed mood and raise treatment effect for depression patients.
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AIM:To explore the roles of brain-stem auditory evoked potential(BAEP) in early monitoring the hearing loss and brain damages in hyperbilirubinemia and nitric oxide(NO) in the pathogenesis of bilirubin-induced hearing loss and brain damages.METHODS:Different doses of bilirubin solution(30 mg/kg,60 mg/kg,90 mg/kg,120 mg/kg and 150 mg/kg) were injected into the abdominal cavity of 15-day old SD rats to make the animal model of hyperbilirubinemia.The serum concentrations of bilirubin were detected by a micro-gauge.The bilirubin concentrations in the brain tissues were examined via a diazo method.The Na+-K+ATPase activities in the brain tissues were analyzed by rooting phosphorus.The NO contents in the brain tissues were assayed via the method of nitrate reductase.BAEP were recorded with an evoked potential recorder.RESULTS:After making the ejection,parts of the rats in the high dosage groups(120 mg/kg and 150 mg/kg) showed the abnormal neuro-behaviors.After 6 hours of the ejection,the bilirubin concentrations in serum and in brain tissues,and NO contents in the brain tissues were increased significantly.The Na+-K+ATPase activities in the brain tissues were decreased obviously,and the PL and IPL of BAEP were prolonged significantly in all the experimental rats except the ones in low dosage group(30 mg/kg).The changes of them were closely related to the dose of injected bilirubin.CONCLUSION:The PL and IPL of BAEP are the objective and sensitive indexes for early monitoring the hearing loss and brain damages in hyperbilirubinemia.NO may plays a certain role in the pathogenesis of bilirubin induced hearing loss and brain damages.