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.     

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。     

含左氧氟沙星及卷曲霉素方案治疗耐多药肺结核近期疗效分析

目的　观察和评价含左氧氟沙星和卷曲霉素联合化疗方案在耐多药肺结核 (MDR PTB)治疗中的疗效。方法　将 177例MDR PTB患者分为治疗组 88例和对照组 89例。化疗方案 :治疗组以左氧氟沙星和卷曲霉素为主 ,联合利福喷汀、异烟肼、对氨基水杨酸钠、吡嗪酰胺 ;对照组用链霉素、乙胺丁醇 ,联用药物同治疗组 ,疗程均为 2 1个月。结果　共有 16 1例患者完成化疗疗程 ,治疗组 82例 ,痰菌阴转率 83% ;对照组 79例 ,痰菌阴转率 5 8% ;痰菌阴转率治疗组明显高于对照组 (P <0 0 1) ;治疗组病灶显效率 5 0 % ,空洞闭合率 6 3% ,治疗组优于对照组 (P <0 0 1) ;治疗组的药物不良反应率为 31% ,对照组为 35 % ,两组比较差异无显著性 (P >0 0 5 )。结论　含左氧氟沙星和卷曲霉素的方案治疗MDR PTB ,有助于痰菌阴转和病变吸收好转 ,药物不良反应低 ,值得在临床上推广应用     

bevacizumab治疗乳腺癌的基础和临床研究

分子靶向药物bevacizumab是针对血管内皮生长因子(VEGF)的重组人源化单克隆抗体,在多种恶性肿瘤的治疗中显示了临床效果。现就bevacizumab的作用机制及其在乳腺癌治疗中的临床研究进展作一综述。     

庆大霉素对豚鼠前庭上皮IGF-1及其受体表达的影响

目的：研究庆大霉素对豚鼠前庭上皮胰岛素样生长因子-1（insulin-like growth factor-1，IGF-1）及其受体（insulin-like growth factor-1 receptor，EGF-1R）表达的影响，并探讨其生物学特性。方法：采用免疫组织细胞化学方法，以抗IGF-1及IGF-1R抗体为标记物，检测庆大霉素损伤后豚鼠前庭上皮自发修复期IGF-1及IGF-1R的表达变化和分布特点；采用Brdu体内标记和抗Brdu抗体免疫组化染色，检测庆大霉素损伤后豚鼠前庭上皮增殖的变化。结果：IGF-1及IGF-1R在正常成年豚鼠前庭上皮细胞中有低水平表达，庆大霉素损伤后，其表达增多。在1d组IGF-1及IGF-1R表达最强，其后逐渐减少。在正常对照组中无Brdu阳性细胞。各实验组均观察到Brdu阳性细胞，7d组最多。结论：庆大霉素损伤后，豚鼠前庭上皮IGF-1及IGF-1R表达增强，其时程变化与细胞增殖活动密切相关。IGF-1在豚鼠前庭上皮损伤后的细胞增殖中可能起重要信号转导作用。     

Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

Stroke is a debilitating disease that affects millions each year.While in many cases cerebral ischemic in jury can be limited by effectivw resuscitation or thrombolytic treatment,the injured neurons wither in a process known as delayed neuronal death(DND).Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered.Of particular interest are two groups of signal proteins that participate in apoptosis-cyclin dependent kinases(CDKs) and p53-among a myriad of signaling events after an ischemic insult.Recent investigations have shown that CDKs,a family of enzymes initially known for their role in cell cycle regulation,are activated in injured neurons in DND.As for p53,new reports suggest that its up-regulation may represent a failed attempt to rescue in jured neurons,although its up-regulation was previously considered an indication of apoptosis.These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage.In this review,the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre-clinical data to explore CDK inhibition as a potential neuroprotective target.Finally,using CDK inhibition as an example,this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic in jury.     

偏瘫病人下肢功能康复阻碍因素初探

观察了10项因素对偏瘫病人下肢功能康复的影响,其结果表明:①下肢功能水平;②平衡功能障碍;③足下垂内翻;④髋关节屈曲外旋挛缩;⑤深感觉障碍;⑥疼痛等几项因素对偏瘫病人下肢功能康复有显著的影响。