The angiotensin receptor blocker losartan reduces coronary arteriole remodeling in type 2 diabetic mice

Cardiovascular complications are a leading cause of morbidity and mortality in type 2 diabetes mellitus (T2DM) and are associated with alterations of blood vessel structure and function. Although endothelial dysfunction and aortic stiffness have been documented, little is known about the effects of T2DM on coronary microvascular structural remodeling. The renin–angiotensin–aldosterone system plays an important role in large artery stiffness and mesenteric vessel remodeling in hypertension and T2DM. The goal of this study was to determine whether the blockade of AT₁R signaling dictates vascular smooth muscle growth that partially underlies coronary arteriole remodeling in T2DM. Control and db/db mice were given AT₁R blocker losartan via drinking water for 4 weeks. Using pressure myography, we found that coronary arterioles from 16-week db/db mice undergo inward hypertrophic remodeling due to increased wall thickness and wall-to-lumen ratio with a decreased lumen diameter. This remodeling was accompanied by decreased elastic modulus (decreased stiffness). Losartan treatment decreased wall thickness, wall-to-lumen ratio, and coronary arteriole cell number in db/db mice. Losartan treatment did not affect incremental elastic modulus. However, losartan improved coronary flow reserve. Our data suggest that Ang II–AT₁R signaling mediates, at least in part, coronary arteriole inward hypertrophic remodeling in T2DM without affecting vascular mechanics, further suggesting that targeting the coronary microvasculature in T2DM may help reduce cardiac ischemic events.     

The Impact of Testosterone on the QT Interval: A Systematic Review

Humans and mammals have sex-specific differences in cardiac electrophysiology, linked to the action of sex hormones in the cardiac muscle. These hormones can upregulate or downregulate the expression of ionic channels modulating the cardiac cycle through genomic and non-genomic interactions. Systematic search in PubMed, Medline and EMBASE including keywords pertaining to testosterone and QT interval. Included experimental studies and observation studies and case reports presenting the results of testosterone administration, excess or deficiency in humans and animals. Testosterone has been shown to shorten the action potential duration, by enhancing the expression of K⁺ channels and downregulating I_CaL increasing the repolarization reserve of the cardiac muscle. This effect has been observed in both genders and animals. Testosterone deficient states can promote arrhythmogenesis. The evidence in this paper may be used to guide clinical considerations, such as increased clinical surveillance of patients in testosterone deficient states using ECG.     

Genomic and phenotypic delineation of congenital microcephaly

PurposeCongenital microcephaly (CM) is an important birth defect with long term neurological sequelae. We aimed to perform detailed phenotypic and genomic analysis of patients with Mendelian forms of CM.MethodsClinical phenotyping, targeted or exome sequencing, and autozygome analysis.ResultsWe describe 150 patients (104 families) with 56 Mendelian forms of CM. Our data show little overlap with the genetic causes of postnatal microcephaly. We also show that a broad definition of primary microcephaly —as an autosomal recessive form of nonsyndromic CM with severe postnatal deceleration of occipitofrontal circumference—is highly sensitive but has a limited specificity. In addition, we expand the overlap between primary microcephaly and microcephalic primordial dwarfism both clinically (short stature in >52% of patients with primary microcephaly) and molecularly (e.g., we report the first instance of CEP135-related microcephalic primordial dwarfism). We expand the allelic and locus heterogeneity of CM by reporting 37 novel likely disease-causing variants in 27 disease genes, confirming the candidacy of ANKLE2, YARS, FRMD4A, and THG1L, and proposing the candidacy of BPTF, MAP1B, CCNH, and PPFIBP1.ConclusionOur study refines the phenotype of CM, expands its genetics heterogeneity, and informs the workup of children born with this developmental brain defect.     

Influenza vaccination and the endurance against air pollution among elderly with acute coronary syndrome

ObjectiveAir pollution, weather condition and influenza are known risk factors of acute coronary syndrome (ACS) among elderly people. The influenza vaccine (IV) has been shown to reduce major cardiovascular events. The purpose of this study was to compare resistance to air pollution and weather factors causing ACS between vaccinated and less-vaccinated elderly people.MethodsA case–crossover design was applied to 1835 elderly ACS patients who were obtained from the 1-million sample of Taiwan National Health Insurance Research Data with inclusion criteria: (1) the first diagnosis of ACS was in cold season and at age 68 or more, (2) had received the free IV program at least once during the period 3 years before the ACS. They were stratified into two groups: 707 had received flu vaccinations for all the 3 years and the remaining 1128 had not. The measurements of air pollutants, temperature, and humidity corresponding to each of the 3 days prior to the ACS diagnosis date were retrieved from the data banks of the Taiwan Environmental Protection Administration and Central Weather Bureau.FindingsIncreases in air pollution concentrations of CO, NO₂, PM₁₀ or PM_2.5 and decreases in temperature significantly influenced the risk of ACS for the non-continuously vaccinated elderly population; however, less significant effects were observed for the continuously vaccinated population.ConclusionConsecutive influenza vaccination may potentially offer resistance against the detrimental effects of air pollution and changes in temperature in frail elderly adults with ACS. Future studies are needed to directly assess the interaction effect between the vaccination and environmental factors on ACS.     

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。     

白血病病人骨髓抑制期实施防感染措施时机的研究

目的 :研究白血病病人在化疗期间 ,不同时间实施预防感染护理的效果。方法 :对照组在化学疗法结束后给予预防感染的护理措施 ,实验组在化学疗法开始前 3～ 7d实施预防性护理措施。观察两组病人感染发生率。结果 :感染发生率实验组明显低于观察组。结论 :在化学疗法开始前实施预防性护理措施有助于降低感染发生率     

PTEN基因敲除降低辐射敏感性及其机制

目的 探讨PTEN基因敲除对辐射敏感性的影响及机制。方法 采用流式细胞术检测MEF1和MEF1/PTEN^－/－细胞内ROS水平;采用Western blot方法,检测H₂O₂和DPI预处理后AKT激酶的表达变化;采用细胞克隆形成率试验分析细胞对⁶⁰Co γ射线的敏感性。结果 PTEN基因敲除后细胞ROS水平增加,辐射敏感性降低。H₂O₂和DPI预处理后影响MEF1细胞AKT激酶活性,但对MEF1/Pten^－/－细胞无影响。 结论 PTEN基因敲除阻断了ROS对AKT的介导,AKT激酶持续活化,可能是辐射敏感性降低的重要原因。     

应用地理信息系统分析中国肾综合征出血热的空间分布

目的　利用地理信息系统 (GIS)技术分析中国大陆肾综合征出血热 (HFRS)的空间区域分布 ,建立HFRS危险区域分布图。方法　收集中国 41个HFRS监测点 1 995～ 1 998年的人群发病资料建立数据库 ,以中国省级、县级、一级河流数字地图为背景 ,在ArcGIS软件的支持下 ,与建立的数据库关联并对监测点人群发病资料进行反距离权重插值分析 ;收集 1 998年 6月SPOT4卫星覆盖东南亚地区的植被影像 ,逐一提取出各监测点监测区域的归一化植被指数 (NDVI) ,与 1 995～ 1 998年HFRS监测点人群平均发病率进行相关分析 ;根据不同流行强度监测区域的NDVI值 ,对遥感影像使用不同的颜色进行密度分割。结果　HFRS监测点人群发病资料的空间分析预测模型显示 ,中国HFRS主要分布于黑龙江流域、黄河中下游地区、长江中下游地区及京杭大运河 淮河流域地区 ,与1 995～ 1 998年全国各县HFRS平均发病率分布图进行比较 ,发现两者基本一致 ;相关分析显示HFRS发病率与NDVI之间呈现正相关 (r=0 .41 7,P <0 .0 1 ) ,根据各监测点NDVI的差异建立了中国HFRS危险区域分布图。结论　根据监测点数据采用GIS技术建立的预测模型对预测全国HFRS的分布情况有重要意义