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Objective To investigate the association of GNA 11 gene polymorphisms with idiopathic hypoparathyroidism (IHP) and its complications. Methods Two hundred and three patients with IHP and 209 control subjects were recruited at Peking Union Medical College Hospital from December 1987 to December 2015. The GNA11 gene polymorphisms were selected and genotyped by Sequenom MassArray iPLEX system.Results The minor allele T of rs308060 was associated with an increased risk of IHP in the additive [OR = 2.505(1.005-6.245) , P＜0.05; OR=3.269(1.264-8.458), P＜0.05]and recessive model[OR= 2.727(1.105-6.727), P＜0.05]. Although no significant difference was found in the incidence of intracranial calcification and cataract in IHP patients, the haplotype CTCGCT consisting of minor allele T of rs308060 was correlated with their 24 hours urinary calcium levels (β = 0. 186, P＜0.05). Conclusions The minor allele T of rs308060 in GNA11 means high risk of IHP, and is positively correlated with urinary calcium excretion in IHP patients after treatment with oral calcium and vitamin D analogs supplements.
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Objective:To analyze that if the quality of ethics review is closely related to the protection of human subjects' right and interest. Methods:This article has analyzed all the issues raised by local Ethics Committee in the process of review in recent two years since guideline of ethical review of drug clinical trials was published, summed up the most common problems occurred in protocols and informed consents. Results:Total 94 new drug or medical device clinical trial projects were reviewed by the local ethics committee, among which 29 projects were ap-proved through regular full board meeting, the approval rate in the initial review was 31%. The most common prob-lems in protocols include: the research backgrounds, design, and risk-benefit ratio; Main issues raised on in-formed consent focused on the contents, language and signature terms. Conclusions:The protection of subjects needs more improvement of capability of investigator, sponsor, drug clinical trial institution and the ethics commit-tee.
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Objective To explore the application of heteroscedastic time series model to the analysis of data of infectious diseases.Methods ARIMA and AR-GARCH models were used to fit the incidence of gonorrhea.Results The time series in this study,which was heteroscedastic significantly,finally was well fitted by AR(1)-GARCH(0,1) model through model selecting.Conclusions AR-GARCH model is suitable for analyzing heteroscedastic time-series data of infectious diseases.
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<p><b>BACKGROUND</b>QacA, a main exporter mediating the multidrug-resistance of Staphylococcus aureus to a variety of antiseptics and disinfectants, possesses a topology of 14 alpha-helical transmembrane segments (TMS). Our study aimed to determine the importance and topology of amino acid residues in and flanking the cytoplasmic end of TMS5.</p><p><b>METHODS</b>Site-directed mutagenesis was used to mutate 5 residues, including L146, A147, V148, W149 and S150, into cysteine. A minimum inhibitory concentration (MIC) and transport assay with or without N-ethylmaleimide (NEM) were performed to analyse the function of these mutants.</p><p><b>RESULTS</b>All of the mutants showed comparable protein expression levels. MIC analysis suggested that mutant W149C showed low resistance levels to the drugs, but the mutations at L146, A147, V148, and S150C had little or no effect on the resistance level. And the results of the fluorimetric transport assay were in agreement with those of MIC analysis, that is to say, W149C did not allow transport to the substrates to be tested, while the other mutants retained significant transport ability. The reaction of the different mutant proteins with Fluorescein-NEM revealed that the mutant L146C was highly reactive with NEM; the W149C and S150C mutants were moderately reactive; A147C was barely reactive and V148C showed no reactivity.</p><p><b>CONCLUSIONS</b>The study identified that residues W149 and S150 situated at the interface of the aqueous: lipid junction as functionally important residues, probably involved in the substrate binding and translocation of QacA.</p>