Health Care-seeking Behaviors in Mosuo and Pumi People in Yunnan Ninglang / 中国医学科学院学报

Objective To investigate the health care-seeking behaviors of Mosuo and Pumi people.Methods The subjects were enrolled by using the multi-stage stratified random sampling method and surveyed by the self-designed questionnaire.Results To tally 1669 subjects including 1121 Mosuo people and 548 Pumi people completed the survey.When Mosuo and Pumi people suffer from ailments,they preferred to buy drugs in drugstores(47.3% for Mosuo and 46.9% for Pumi),followed by visiting a local township hospital(27.0% for Mosuo and 24.3% for Pumi).When they suffered from severe diseases,they preferred to visit the county/city/state hospital(93.4% for Mosuo and 91.1% for Pumi).The mental disease were mainly treated in the county/city/state hospitals(49.3% for Mosuo and 52.7% for Pumi);notably,39.3% of the Mosuo respondents and 31.5% of the Pumi respondents skipped this question.Conclusion Health education,including awareness-raising activities on mental health,should be enhanced in Mosuo and Pumi people to further improve their health care-seeking behaviors.

Association between Polymorphisms of rs3924999,rs35753505 in NRG1 Gene and the Efficacy of Risperidone in Patients with Schizophrenia / 昆明医科大学学报

Objective To investigate the association between polymorphisms of rs35753505, rs3924999in neuregulin－1 (NRG1) gene and the efficacy of risperidone after 12 weeks treatment in Han patients with schizophrenia from Yunnan of China.Methods A case－control study was conducted: 114 schizophrenic Han inpatients with 12 weeks single therapy of risperidone were randomly selected from July 2012 to March 2013 and 187 normal Han persons whose age and years of education matched the controls.TaqMan allelic genotyping technology was used to analyze NRG1 genotyping.Treatment effect of risperidone was evaluated by the positive and negative symptoms scale (PANSS), PSP, Raven’s Standard Progressive Matrices, Wechsler Intelligence Scale and Number Cancellation Test.Results (1) There was no statistically difference in genotypes, allele frequencies of rs35753505, rs3924999 polymorphic locibetween schizophrenic inpatients and normal persons. (2) The baseline clinical data of patients with schizophrenia in different NRG1 gene polymorphism was not significant. (3) The value difference of Number Cancellation Test One between pre and post treatment of risperidone was related with different genotypes of two polymorphismsin NRG1 gene, there was statistically difference in two genotypes of rs35753505 loci: G/A group was higher than G/G group (P=0.010) and in three genotypes of rs3924999 loci: A/A group was higher than A/G group (P=0.032) . (4) The value difference of Reven's Standard Progressive Matrices between pre and post treatment of risperidone was related with rs35753505 polymorphic loci: G/A group was higher than G/G group (P=0.004) (5) The result of correlation regression analysis between pre and post treatment of risperidone showed that the value difference of Number Cancellation Test Two was related with the baseline clinical data of course,dose,immediate memory,net score of Number Cancellation Test Two,Number Cancellation Test Three and the genotypes of rs35753505 loci.Conclusion After 12 weeks treatment of risperidone: the improvement degree of patients'attention directivity and concentrated force in different genotypes of rs35753505loci was different:G/A group was higher than G/G group.

Discovery and structural optimization of 1-phenyl-3-(1-phenylethyl)urea derivatives as novel inhibitors of CRAC channel.

AIM: Ca(2+)-release-activated Ca(2+) (CRAC) channel, a subfamily of store-operated channels, is formed by calcium release-activated calcium modulator 1 (ORAI1), and gated by stromal interaction molecule 1 (STIM1). CRAC channel may be a novel target for the treatment of immune disorders and allergy. The aim of this study was to identify novel small molecule CRAC channel inhibitors. METHODS: HEK293 cells stably co-expressing both ORAI1 and STIM1 were used for high-throughput screening. A hit, 1-phenyl-3-(1-phenylethyl)urea, was identified that inhibited CRAC channels by targeting ORAI1. Five series of its derivatives were designed and synthesized, and their primary structure-activity relationships (SARs) were analyzed. All derivatives were assessed for their effects on Ca(2+) influx through CRAC channels on HEK293 cells, cytotoxicity in Jurkat cells, and IL-2 production in Jurkat cells expressing ORAI1-SS-eGFP. RESULTS: A total of 19 hits were discovered in libraries containing 32 000 compounds using the high-throughput screening. 1-Phenyl-3-(1-phenylethyl)urea inhibited Ca(2+) influx with IC50 of 3.25±0.17 µmol/L. SAR study on its derivatives showed that the alkyl substituent on the α-position of the left-side benzylic amine (R1) was essential for Ca(2+) influx inhibition and that the S-configuration was better than the R-configuration. The derivatives in which the right-side R3 was substituted by an electron-donating group showed more potent inhibitory activity than those that were substituted by electron-withdrawing groups. Furthermore, the free N-H of urea was not necessary to maintain the high potency of Ca(2+) influx inhibition. The N,N'-disubstituted or N'-substituted derivatives showed relatively low cytotoxicity but maintained the ability to inhibit IL-2 production. Among them, compound 5b showed an improved inhibition of IL-2 production and low cytotoxicity. CONCLUSION: 1-Phenyl-3-(1-phenylethyl)urea is a novel CRAC channel inhibitor that specifically targets ORAI1. This study provides a new chemical scaffold for design and development of CRAC channel inhibitors with improved Ca(2+) influx inhibition, immune inhibition and low cytotoxicity.

UNC-31/CAPS docks and primes dense core vesicles in C. elegans neurons.

UNC-31 or its mammalian homologue, Ca(2+)-dependent activator protein for secretion (CAPS), is indispensable for exocytosis of dense core vesicle (DCV) and synaptic vesicle (SV). From N- to the C-terminus, UNC-31 contains putative functional domains, including dynactin 1 binding domain (DBD), C2, PH, (M)UNC-13 homology domain (MHD) and DCV binding domain (DCVBD), the last four we examined in this study. We employed UNC-31 null mutant C. elegans worms to examine whether UNC-31 functions could be rescued by ectopic expression of full length UNC-31 vs each of these four domain-deleted mutants. Full length UNC-31 cDNA rescued the phenotypes of C. elegans null mutants in response to Ca(2+)-elevation in ALA neurons. Surprisingly, MHD deletion also rescued UNC-31 exocytotic function in part because the relatively high Ca(2+) level (pre-flash Ca(2+) was 450 nM) used in the capacitance study could bypass the MHD defect. Nonetheless, the three other domain-truncation cDNAs had almost no rescue on Ca(2+) evoked secretion. Importantly, this genetic null mutant rescue strategy enabled physiological studies at levels of whole organism to single cells, such as locomotion assay, pharmacological study of neurotransmission at neuromuscular junction, in vivo neuropeptide release measurement and analysis of vesicular docking. Our results suggest that each of these UNC-31 domains support distinct sequential molecular actions of UNC-31 in vesicular exocytosis, including steps in vesicle tethering and docking that bridge vesicle with plasma membrane, and subsequently priming vesicle by initiating the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) core complex.

Insulin-like signaling pathway functions in integrative response to an olfactory and a gustatory stimuli in Caenorhabditis elegans.

Animals integrate various environmental stimuli within the nervous system to generate proper behavioral responses. However, the underlying neural circuits and molecular mechanisms are largely unknown. The insulin-like signaling pathway is known to regulate dauer formation, fat metabolism, and longevity in Caenorhabditis elegans (C. Elegans). Here, we show that this highly conserved signaling pathway also functions in the integrative response to an olfactory diacetyl and a gustatory Cu(2+) stimuli. Worms of wild-type N2 Bristol displayed a strong avoidance to the Cu(2+) barrier in the migration pathway to the attractive diacetyl. Mutants of daf-2 (insulin receptor), daf-18 (PTEN lipid phosphatase), pdk-1 (phosphoinositide-dependent kinase), akt-1/-2 (Akt/PKB kinase) and sgk-1 (serum- and glucocorticoid-inducible kinase) show severe defects in the elusion from the Cu(2+). Mutations in DAF-16, a forkhead-type transcriptional factor, suppress the integrative defects of daf-2 and akt-1/-2 mutants. We further report that neither cGMP nor TGFß pathways, two other dauer formation regulators, likely plays a role in the integrative learning. These results suggest that the insulin-like signaling pathway constitutes an essential component for sensory integration and decision-making behavior plasticity.

[Automatical updating the application software on the hospital information system's client].

In view of the current predicament of updating the application software on the hospital information system's client, the Synchronizer module in PowerBuilder is used in combination with some techniques of the windows operation system, in order to implement automatic synchronistic updating of the application software on the Hospital Information System's client before the program's running.