非综合征型聋患儿及其家庭成员常见耳聋基因变异分析

目的分析深圳地区非综合征型耳聋患者及其相关高危人群中常见耳聋基因变异位点的分布，为分子诊断、遗传咨询及流行病学研究提供依据。方法应用基质辅助激光解析电离飞行质谱方法，对深圳地区1~6岁语前聋患儿71例及其听力正常的家庭成员（耳聋高危人群）145例，和作为对照听力的正常人群200例进行GJB2、SLC26A4、GJB3及MT RNR1基因的20个变异位点的检测。结果常见耳聋基因热点变异的检出率在语前聋患儿中为37%（26/71），在高危人群中为28%（40/145），在正常健康人群中为4.5%（9/200）；GJB2热点变异检出率在语前聋患儿中为18%（13/71），在高危人群中为12%（17/145），在正常人群中为2%（4/200）；SLC26A4检出率在语前聋患儿中为18%（13/71），在高危人群中为16%（23/145），在正常人群中为2.5%（5/200）。语前聋患儿组和耳聋高危人群组之间GJB2和SLC26A4变异检出率没有统计学意义（P=0.209），但两者都显著比正常人群高（P均<0.0001）；语前聋患儿中GJB2和SLC26A4变异纯合子和复合杂合子占18%（13/71），耳聋高危人群和正常人群中均未发现纯合子和复合杂合子，与语前聋患儿组比较有统计学意义（P<0.0001）。GJB3和MT RNR1变异在语前聋患儿、高危人群和正常人群中均未发现。结论GJB2和SLC26A4纯合和复合杂合变异是深圳地区语前聋患儿的重要致病原因，其中最常见的变异位点是GJB2:c.235delC和SLC26A4:c.919 2A>G。对于仅检出单杂合变异的耳聋患儿，可进行相应基因的测序，进一步明确分子诊断。     

Determination of plasma antiglycan autoantibodies in patients with IgA nephropathy and the correlation with clinical characteristics

Objective To establish the measurement of IgA1 O-glycan-specific antiglycan autoantibodies in patients with IgA nephropathy (IgAN), and evaluate their role in the development and progression of IgAN. Methods In the IgAN regular follow-up cohort of Peking University Institute of Nephrology from January 2006 to December 2015, 170 patients drawn by stratified randomization were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma galactose-deficient IgA1 (Gd-IgA1) and antiglycan autoantibody (IgG and IgA1). The correlation between antiglycan autoantibodies and clinicopathological parameters was analyzed by linear correlation and multiple linear regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the value of plasma anti glycide antibodies in the diagnosis of IgAN. Results IgG and IgA1 antiglycan autoantibodies that specifically recognized Fab-hinge region (Fab-HR) antigens could be detected in both IgAN and healthy control group. Agglutinin inhibition test showed that the specific antigen epitope was N-acetylgalactosamine (GalNAc) residue exposed to galactose deficiency in IgA1 hinged region. There was no significant difference in the absolute levels of plasma IgG antiglycan autoantibodies between IgAN and healthy controls (P=0.963). After adjustment of the plasma level of IgG, the normalized antiglycan autoantibody (ln[IgG antiglycan antibody/IgG]) in patients with IgAN was significantly higher than that in healthy controls (0.58±0.31 vs 0.37±0.11, P﹤0.01). The normalized level of IgG antiglycan autoantibody in IgAN patients was positively correlated with 24 h urine protein level during renal biopsy (Spearman r=0.183, P﹤0.05), and was also significantly correlated with 24 h urinary protein level after adjusting for baseline clinical and pathological factors (β=0.713, 95%CI 0.323-1.102, P﹤0.01). The area under ROC curve (AUC) of normalized IgG antiglycan autoantibody in the diagnosis of IgAN was 0.764 (95% CI 0.682-0.845, P﹤0.05). Using the cut-off value of 0.396, the sensitivity and specificity of normalized IgG antiglycan autoantibody for IgAN were 0.729 and 0.700 respectively. There was no significant difference in the absolute or normalized levels of IgA1 antiglycan autoantibodies between IgAN patients and healthy controls. Conclusions Gd-IgA1-specific antiglycan autoantibodies can be detected both in IgAN patients and healthy controls. They are elevated in some patients with IgAN and possibly involved in the development of IgAN.     

Impact of red blood cell transfusion on acute coronary syndrome: a meta-analysis

The impact of red blood cell transfusion on outcomes in patients with acute coronary syndrome is controversial. Pubmed, EMBASE, and Cochrane Library were searched for studies of red blood cell transfusion and acute coronary syndrome that were published in any language, from January 1, 1966, to April 1, 2016. We analyzed 17 observational studies, of 2,525,550 subjects. We conducted a systematic review with meta-analysis of studies assessing the association between blood transfusion and the risk for all-cause mortality and reinfarction. The search yielded 17 observational studies, of 2,525,550 subjects, during a study follow-up period, ranging from 30 days to 5 years. Red blood cell transfusion compared with no blood transfusion is associated with higher short- and long-term all-cause mortality as well as reinfarction rates (adjusted RR 2.23; 95% CI 1.47–3.39; HR 1.93; 95% CI 1.12–3.34; RR 2.61; 95% CI 2.17–3.14, respectively). In hemoglobin-stratified analyses, a graded association between red blood cell transfusion and mortality was observed, transfusion and risk of all-cause mortality was borderline significant at hemoglobin levels below 8.0 g/dL (RR 0.52; 95% CI 0.25–1.06), and was associated with an increased risk of mortality at a hemoglobin above 10 g/dL (RR 3.34; 95% CI 2.25–4.97). Red blood cell transfusion was associated with an increased risk of short- and long-term mortality as well as myocardial reinfarction. However, transfusion appeared to have beneficial or neutral effects on mortality at hemoglobin levels below 8.0 g/dL, and harmful effects above 10 g/dL. A large definitive randomized controlled trial addressing this issue is urgently required.     

本草纲目药物警戒数据库设计与应用研究

目的:为深入分析研究本草纲目中的药物警戒思想提供新方法。方法:基于本草纲目金陵本文献著作设计了药物警戒数据库,阐述了数据库建立的要求和存储模型的选取,以及数据库的概念和逻辑设计。结果:在此数据库的基础上可建立知识发现系统,应用数据挖掘算法,对本草纲目中的药物警戒思想进行分析。结论:本草纲目药物警戒思想数据库的建立可以为深入研究药物警戒思想提供方便、准确的手段,此方法也可应用于其他文献著作研究。     

齐拉西酮与奥氮平治疗早期精神分裂症的效果及安全性比较

目的 探讨齐拉西酮与奥氮平治疗早期精神分裂症的效果及安全性.方法 将本院收治100例早期精神分裂症患者随机分为对照组与实验组,各50例.对照组给予奥氮平治疗,试验组给予齐拉西酮治疗.比较两组临床疗效、自我管理能力等差异.结果 试验组总有效率为92.0％,高于对照组的88.0％,差异无统计学意义(P＞0.05).治疗后,试验组自我管理能力为(73.68±5.31)分,高于对照组的(60.66±4.37)分;试验组不良反应率为4.0％,低于对照组的20.0％;差异均具有统计学意义(均P＜0.05).结论 齐拉西酮较奥氮平治疗早期精神分裂症效果佳,值得临床选择.     

Therapeutic effects of induced pluripotent stem cells in chimeric mice with β-thalassemia

Although β-thalassemia is one of the most common human genetic diseases, there is still no effective treatment other than bone marrow transplantation. Induced pluripotent stem cells have been considered good candidates for the future repair or replacement of malfunctioning organs. As a basis for developing transgenic induced pluripotent stem cell therapies for thalassemia, β⁶⁵⁴ induced pluripotent stem cells from a β⁶⁵⁴ -thalassemia mouse transduced with the normal human β-globin gene, and the induced pluripotent stem cells with an erythroid-expressing reporter GFP were used to produce chimeric mice. Using these chimera models, we investigated changes in various pathological indices including hematologic parameters and tissue pathology. Our data showed that when the chimerism of β⁶⁵⁴ induced pluripotent stem cells with the normal human β-globin gene in β⁶⁵⁴ mice is over 30%, the pathology of anemia appeared to be reversed, while chimerism ranging from 8% to 16% provided little improvement in the typical β-thalassemia phenotype. Effective alleviation of thalassemia-related phenotypes was observed when chimerism with the induced pluripotent stem cells owning the erythroid-expressing reporter GFP in β⁶⁵⁴ mouse was greater than 10%. Thus, 10% or more expression of the exogenous normal β-globin gene reduces the degree of anemia in our β-thalassemia mouse model, whereas treatment with β⁶⁵⁴ induced pluripotent stem cells which had the normal human β-globin gene had stable therapeutic effects but in a more dose-dependent manner.