OBJECTIVE:To establish a method for the quality control of Jiuweiniuhuang pills.METHODS:TLC was applied for the quantitative identification of Bostaurus domesticus,Carthamus tinctorius and Aucklandia lappa in this prescription as well as the testing of the limit of Aristolochic acid A. RP-HPLC method was established for determination of Costunolide and Dehydrocostuslactone.RESULTS: The TLC spots were clear,well-separated,specific and free from interference of negative sample. The content of Aristolochic acid A which stood at less than 2.5 ?g?6 g-1 was up to the standard.Costunolide showed a linear relationship at the concentration range of 0.26～1.3 ?g with an average recovery of 99.8% (RSD=1.1%,n=6); and Dehydrocostuslactone showed a linear relationship at the concentration range of 0.258～1.29 ?g with an average recovery of 98.2%(RSD=1.7%,n=6).CONCLUSION: The method is suitable for the quality control of Jiuweiniuhuang pills.

Objective To investigate the correlations of P2Y12 gene polymorphisms with clopidogrel resistance and long-term outcome in patients with acute ischemic stroke. Methods From June 2015 to June 2017, consecutive patients with acute ischemic stroke admitted to the Department of Neurology, Nanjing Jiangbei People's Hospital were enrolled. Thromboelastography was used to measure platelet inhibition rate and assess clopidogrel resistance. Polymerase chain reaction was used to assay C34T and G52T polymorphisms of P2Y12 gene. The patients were followed up at 12 months after discharge. The primary outcome was combined outcome of stroke recurrence, myocardial infarction, and death due to cardiocerebrovascular events. Results A total of 214 patients were enrolled, 51 (23.8%) had clopidogrel re-sistance and 29 (13.4%) had major outcome events. One hundred twenty-eight (59.8%) patients were C34T CC genotype and 86 (40.2%) were CT+TT genotype. The proportion of clopidogrel resistance in patients with CT+TT genotype was significantly higher than that with CC genotype ( 76.5% vs.28.8%;χ2=25.672, P=0.001). There were 131 patients (61.2%) with G52T GG genotype and 83 (38.8%) with GT+TT genotype. There was no significant difference in the proportion of clopidogrel resistance between the GT+TT genotype and the GG genotype (43.1% vs.37.4%; χ2=0.534, P=0.465). Multiple logistic regression analysis indicated that age (odds ratio [OR] 1.064, 95%confidence interval [CI] 1.009-1.115;P=0.021), diabetes ( OR 3.773, 95%CI 1.672-8.475; P=0.004), and C34T CT+TT genotype ( OR 9.087, 95%CI 4.416-22.665; P=0.002) were the independent risk factors fot clopidogrel resistance. Cox proportional hazards model analysis showed that age (Hazard ratio [HR] 1.058, 95%CI 1.001-1.121; P=0.049), hypertension ( HR 3.105, 95%CI 1.149-9.523; P=0.028), homocysteine ( HR 1.101, 95%CI 1.020-1.190; P=0.014), and C34T CT+TT genotype ( HR 2.588, 95%CI 1.121-5.967; P=0.026) were independent risk factors for the composite outcome. Conclusion C34T polymorphism of P2Y12 gene in patients with acute ischemic stroke may be a risk factor for clopidogrel resistance and is independently associated with the risk of long-term recurrence of vascular events.

Objective To investigate the prognostic factors relevant to acute low-tone sensorineural hearing loss (ALHL).Methods 196 adult ALHL patients,including 82 males and 114 females with mean age of (43.1 ± 14.3)years old were included.All patients received the same therapy and were evaluated the curative effect.To evaluate the impact factors on the prognosis of hearing,inclusive of age,gender,time delay before the first visit,degree of deafness,vestibular function,electrocochleogram,and the serum levels of thyroxines by SPSS 18.0 software.Results Of those 196 patients with ALHL,124 (63.3％) were recovery,5(2.6％) were excellent better,42(21.4％) were better,and 25 (12.8％) were poor,with a total effective rate of 87.2％.Among 15 (12.1％) who recurred the hearing loss,2 developed into Meniere's disease during the follow-up.The mean age of patients with poor hearing effect was significantly older than that of other patients (P ＜ 0.05).No relativity was found between gender and hearing curative effect.There existed a statistical difference in total effective rate among subjects with different histories (P ＜ 0.05).In addition,the recovery rate was significantly different between groups,i.e.,the course of disease was less than 14 days,between 14 days and 6 months,and between 6 months and 2 years (P ＜0.05).There was no statistical significance in total effective rate among different degrees of deafness (P ＞ 0.05).However,in term of the recovery rate,the difference was statistical significance (P ＜ 0.05).The recovery rate in patients with mild hearing loss was higher than that in middle or heavy hearing loss (both P ＜ 0.05).Among patients with mild deafness,the recovery rate in patients whose history was less than 3 months was significantly higher than that more than 3 months (P ＜ 0.05).For moderate deafness patients,the recovery rate in patients whose history was less than 7 days was significantly higher than that more than 1 month (P ＜ 0.05).There were statistical differences in hearing effect of 130 (66.3％) patients with abnormal vestibular function in comparison to that with normal vestibular function (x2 =15.1,P ＜ 0.05).There were 17(8.7％) patients with abnormal electrocochleogram combined with abnormal vestibular function,and the hearing effects were all poor.There were 45 (23.0％) patients with abnormal thyroxine levels in serum,which was significant higher than that in health adults of 5.9％ (x2 =7.26,P ＜ 0.01).There was no significant difference in hearing prognosis between patients with abnormal and normal thyroxine levels (x2 =2.51,P ＞ 0.05).Conclusions With respect to ALHL,the hearing effect is associated significantly with the history.The severity of hearing loss is negative prognostic factor for hearing recovery.Age,vestibular function,and electrocochleogram might predict hearing recovery.Gender and thyroxine levels couldn't predict the hearing prognosis,although there is a high incidence rate in patients with ALHL.

Objective The transcriptome sequencing results of brain tissues of olanzapine-treated mice were analyzed to screen out differentially-expressed genes and explore potential targets of atypical antipsychotics leading to body weight gain.Methods Twenty female C57BL/6 mice were randomly divided into control group (Ctrl) and Olanzapine administration group (Olz), which were given saline and Olanzapine solution by gavage, respectively. The whole brain tissues were collected 8 weeks later for Transcriptome sequencing (RNA-Seq). The possible targets of olanzapine-induced body weight gain were identified by the Gene Ontology (GO) functional annotation analysis, the Kyoto Encyclopedia of Genes and Gnomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. Differential expression levels of mRNAs were further verified by real-time quantitative fluorescence PCR (RT-qPCR).Results Compared with Ctrl group, 591 differentially expressed genes were screened in Olz group, including 251 up-regulated genes and 340 down-regulated genes. GO analysis showed that differential genes were widely involved in transcriptional process, among which the expression of genes related to the regulation of digestive system and cold-induced thermogenesis were significantly enriched. KEGG analysis showed that differential genes were widely involved in the interaction between neuroactive ligands and receptors, and the differential genes were significantly enriched in oxytocin signaling, fat digestion and absorption, and cholesterol metabolism pathways. RT-qPCR were performed to verify the expression levels of genes enriched in feeding regulation, gastric kinesis, thermogenesis, fat metabolism and other processes (Oxt, Trpv1, Adipoq, Phox2b, Abcg5, Mogat2, Dbh, Plac8 and Neurog1) as well as hub genes in PPI network (Fos, Dusp1 and Egr2), and the results were consistent with the trend of RNA-Seq.Conclusion Olanzapine administration resulted in changes in central feeding regulation, gastrointestinal motility, thermogenesis and other physiological processes in mice, which might be involved in body weight gain induced by olanzapine.

ObjectiveTo explore the beneficial role and potential mechanism of intermittent fasting in olanzapine-induced metabolic disorders. MethodsC57BL/6J mice were randomly divided into four groups: Saline + ad libitum (Saline+Ad libitum), Saline + intermittent fasting (Saline +IF), olanzapine administration + ad libitum (Olanzapine+ Ad libitum), and olanzapine administration + intermittent fasting (Olanzapine+IF)， with eight mice in each group. The IF group adopted the 5∶2 scheme, that is, fasting on Monday and Thursday every week, and eating freely in the rest of the time. Ad libitum feeding as the control of intermittent fasting, Saline gavage as the control of olanzapine administration. The experiment lasted for 12 weeks. The differences of body mass, liver mass and epididymal adipose tissue mass were compared between the olanzapine-treated group and the control group after IF intervention. The body fat mass, lean body mass, and visceral fat infiltration of mice were analyzed by nuclear magnetic resonance and HE staining, respectively. Furthermore, the levels of fasting blood glucose, insulin, and insulin resistance index (HOMA-IR) in the process of glucose metabolism were also measured by glucose oxidase method and radioimmunoassay, respectively. The effects of IF on H₂O₂ release and the level of cytochrome C mRNA, a marker related to mitochondrial damage, were detected by ELISA and real-time fluorescence quantitative PCR. ResultsAfter 12 weeks of treatment, olanzapine induced a significant increase in body mass, body fat, lean body mass and visceral fat infiltration (P<0.05), as well as fasting blood glucose, insulin, and HOMA-IR (P<0.05); however, IF significantly reduced the above indicators (P<0.05). Further studies showed that the release of H₂O₂ and the expression of Cytochrome C mRNA in adipose tissue of mice after intermittent fasting treatment were significantly decreased (P<0.05). ConclusionIntermittent fasting therapy can alleviate olanzapine-induced metabolic disorders in mice. The underlying mechanism may involve the inhibition of oxidative stress level and the maintenance of mitochondrial functions.