Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Bacteroides forsythus ATCC43037菌体蛋白与人类唾液酸性富脯蛋白的相互作用

目的：探讨福赛类杆菌与人类唾液富脯蛋白相互作用的蛋白分子。方法：Western—blot方法。将人工合成唾液富脯蛋白用生物素标记，福赛类杆菌全菌蛋白凝胶电泳，半干转移至纤维膜上，观察二者的相互作用。结果：富脯蛋白能与分子量为85KD、65KD、60KD、以及49KD的福赛类杆菌蛋白发生结合。结论：福赛类杆菌存在与人类唾液富脯蛋白相互结合的粘附素。     

Ligustrazine inhibits high voltage-gated Ca~(2+) and TTX-resistant Na~+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.     

试论加强国际合作与促进我国医学伦理学教育的发展

原北京医科大学(现为北京大学医学部)从20世纪90年代初开始,积极寻求与美国中华医学基金会的合作以促进医学伦理学的学科发展和国际化水平的提高。十几年来,北京大学医学部作为基地和依托极大地支持和引领了我国医学伦理学的教学改革与发展,增强了相关人员的医学伦理意识以及医学伦理学理论对实践的指导作用,促进了伦理学知识和能力的培训,提升了我国生物医学科研伦理的实力,奠定了医学伦理学继续教育的基础,使医学伦理学实现了系统性和跨越式的发展。     

儿童肺炎支原体感染状况分析

目的 探讨儿童的肺炎支原体(MP)感染现状及早期诊断的意义。方法 检测181例就诊儿童血液标本分析MP感染的状况。结果 肺炎支原体感染率为29.8％;男性患儿MP检测阳性率(35.7％)明显高于女性患儿(16.4％)(P<0.01);5岁以下患儿阳性率超过50％,且有3例婴儿检测阳性;10-12月份支原体肺炎发病率明显增加,占全年的40.7％。结论 针对儿童支原体肺炎的发病情况,早诊断,早治疗,利于患儿尽早康复,防止肺部病变迁延及肺外并发症的发生。     

深圳市全人口结核病控制实施效果评价

目的　研究深圳市实施包含非户籍人口在内的全人口结核病控制模式。方法 在全人口中推行以发现和彻底治疗传染性肺结核病为主的现代结核病控制和监测策略。结果 从1993年至2001年,登记涂阳肺结核8483例,治愈率96.3%。肺结核疫情明显下降,深圳市户籍人口涂阳患病率下降55.9%,非户籍人口涂阳患病率下降38.6%。结论 实施全人口结核病控制是必要的、可行的和科学的。     

C反应蛋白测定在小儿败血症中的应用

目的　本研究的目的在了解C反应蛋白的 (CRP)测定对于小儿败血症的诊断价值。方法　连续选取2 0例白细胞总数不高的小儿败血症患者 ,作回顾性研究对象。比较其治疗前和治疗后 7～ 1 0d后疾病的痊愈或明显好转时CRP水平 ,并与体温、白细胞分类结果进行比较。结果　治疗后CRP水平 (0 57± 0 68μg/ml)显著低于治疗前水平 (5 90± 3 57μg/ml) ,P <0 0 0 1 ;治疗前CRP的阳性率为 1 0 0 % ,显著高于嗜中性粒细胞比率 >75 %的阳性率 (30 % )和体温高于 37 5℃的阳性率 (30 % ) ,P <0 0 0 5。结论　CRP可以作为一种反映细菌感染的敏感指标 ,有助于不典型小儿败血症的诊断和疗效观察。