基于生物信息学的肥厚型心肌病易感基因TNNC1单核苷酸多态性致病表型分析

肥厚型心肌病(HCM)是一种常见的遗传性心脏病,是青少年及年轻运动员心源性猝死的最主要原因之一,其分子遗传学基础为基因突变。TNNC1是HCM的重要致病基因之一,目前仅发现其少量非同义单核苷酸多态性(nsSNPs)位点与HCM发病相关,但该基因其他nsSNPs数量较多,结合临床进行实验遗传检测其基因型与表型的关系,工作量巨大,尚不可行。因此,采用生物信息学方法,从dbSNP数据库中筛选出TNNC1基因全部的nsSNPs,联合4款(Mutation Taster、PolyPhen-2、PhD-SNP和MutPred)专业软件,进行有害性分级筛选和致病关联预测,最后进行突变蛋白三维结构建模及可视化分析。结果显示,首次从TNNC1基因102个nsSNPs位点中预测出疾病相关的18个(G159D、S69R、P52R、D149G、D3V、G140E、N51K、D151V、M47R、G110C、A23D、G140R、K158N、C35Y、R147C、L48P、F74C和V44G)高风险nsSNPs。基于生物信息学方法,以TNNC1基因的nsSNPs为示范,分析其nsSNPs与疾病表型的关系,这为其他遗传疾病致病基因nsSNPs的关联分析打下理论研究基础,具有重要的参考价值。     

RWMAs in critically ill patients with non-obstructed coronary arteries

Introduction

Left ventricular (LV) dysfunction is estimated to occur in 10%–25% of the general intensive care unit (ICU) population and is frequently seen as regional wall motion abnormalities (RWMAs). Although RWMA is mostly attributed to myocardial ischemia or infarction, some studies have suggested that nonischemic RWMA might also be prevalent. We sought to establish that RWMA can be seen in critically ill patients with normal coronary arteries and to explore reasons for RWMA in this population.

Methods

In this retrospective study, data from the hospital angiography register and the ICU register were collated between 2012 and 2019. Patients were identified who underwent angiography in conjunction with their ICU stay and had RWMA on echocardiography. Patients were divided into either those with non-obstructed or those with obstructed coronary arteries. Cardiac magnetic resonance imaging (cMRI) examinations were reviewed if they had been performed on patients with non-obstructed coronaries.

Results

We identified 53 patients with RWMA and non-obstructed coronary arteries and 204 patients with RWMA and obstructed coronary arteries. Patients with non-obstructed coronary arteries were more often female, younger, and had fewer cardiovascular risk factors. They less commonly had ST elevation, but more frequently had T-wave inversion or serious arrhythmias. Troponin levels were higher in patients with obstructed coronary arteries, but NT-proBNP was similar between the groups. There were no differences in risk-adjusted 90-day mortality between patients with non-obstructed versus obstructed coronary arteries (OR 1.21, [95% CI 0.56–2.64], p = .628). In those with non-obstructed coronary arteries, follow-up echocardiography was available for 38 patients, of whom 30 showed normalization of cardiac function. Of the 14 patients with non-obstructed coronary arteries on whom cMRI was performed, 7 had a tentative diagnosis of Takotsubo syndrome or myocardial stunning; 4 had a myocardial infarction (preexisting in 3 cases); 1 patient had acute myocarditis; 1 patient had post-myocarditis; and 1 patient was diagnosed with dilated cardiomyopathy.

Conclusion

RWMA can be seen to occur in critically ill patients in the absence of coronary artery obstruction. Several conditions can cause regional hypokinesia, and cMRI is useful to evaluate the underlying etiology.     

Acsl4在浸润性乳腺癌组织中的表达及其临床意义

目的:探讨Acsl4在浸润性乳腺癌组织中的表达及其临床意义。方法:采用免疫组织化学法检测108例浸润性乳腺癌组织中Acsl4的表达。结果:108例浸润性乳腺癌组织中,33例(30.6%)阳性表达,75例(69.4%)阴性表达。组织学G3级的乳腺癌组织中Acsl4阳性率为42.3%(22/52),高于G1+G2级的阳性率(19.6%,11/56),差异具有统计学意义(P<0.05)。ER阳性组织的Acsl4的阳性率15.8%(6/38),低于ER阴性的病例(38.6%,27/70),差异具有统计学意义(P<0.05)。Acsl4的表达与患者年龄、肿瘤大小、淋巴结是否转移、HER2、PR、p53、Ki67的表达情况无统计学意义的相关性(P均>0.05)。结论:Acsl4在浸润性乳腺癌组织中存在异常表达,其阳性表达与乳腺癌患者组织学分级较高及ER阴性表达密切相关。     

微小RNA-148a-3p靶向调控MAP3K9表达及对胃癌细胞增殖和凋亡的影响

目的 探讨微小RNA-148a-3p（miR-148a-3p）对丝裂原活化蛋白激酶激酶激酶9（MAP3K9）的靶向调控作用及对胃癌细胞增殖和凋亡的影响。方法 向对数生长期胃癌细胞株MGC-803转染miR-148a-3p模拟物（mimics组）和阴性对照（NC组），以未转染的MGC-803细胞为对照组；采用实时定量PCR（QPCR）检测各组miR-148a-3p水平以评价转染效率，MTT法检测各组细胞增殖能力，流式细胞术检测各组细胞凋亡情况，分别采用QPCR和Western blotting检测Bcl-2、Bax、caspase-3及MAP3K9 mRNA和蛋白水平，同时采用双荧光素酶报告实验验证miR-148a-3p与MAP3K9的靶向作用关系。结果 QPCR结果显示，对照组、NC组和mimics组的miR-148a-3p水平分别为1.021±0.123、1.087±0.196和2.854±0.368，与对照组和NC组比较，mimics组的miR-148a-3p水平升高（P＜0.05）。mimics组MGC-803细胞的增殖活力较其余两组减弱（P＜0.05）。mimics组MGC-803细胞凋亡率为（15.2±1.6）％，高于对照组的（3.5±0.9％）％和NC组的（4.5±1.1）％，差异具有统计学意义（P＜0.05）。与对照组和NC组比较，mimics组的MAP3K9和Bcl-2的mRNA和蛋白水平均下调，而Bax和caspase-3的mRNA和蛋白水平均上调（P＜0.05）；双荧光素酶报告实验证实MAP3K9是miR-148a-3p的直接作用靶点。结论 MiR-148a-3p可抑制胃癌细胞MGC-803的增殖并诱导其凋亡，可能通过靶向MAP3K9来发挥抑癌作用，调控miR-148a-3p／MAP3K9轴在胃癌防治中有一定应用前景。     

基于中医体质辨识的糖尿病风险评估模型建立与验证

背景　中医体质因素在糖尿病的发生发展过程中具有重要作用，但目前糖尿病的预测预警模型仅涵盖一般人口学资料、客观检查指标、生活方式等内容。在糖尿病风险评估模型中纳入中医体质辨识内容，对有针对性地防治糖尿病的发生发展具有重要意义。目的　根据健康体检数据建立基于中医体质辨识的糖尿病风险模型并对其进行验证。方法　于2016年1月-2018年12月，以2014-2015年某省级综合性医院健康管理中心体检数据为训练集数据（n=30 951），对是否患糖尿病进行单因素和多因素Logistic回归分析，纳入有意义的影响因素指标建立糖尿病风险评估模型；以2016-2017年的健康体检数据作为测试集数据（n=24 061），采用受试者工作特征曲线（ROC）对模型进行验证。结果　训练集人群中，患有糖尿病者1 315例（4.25%），未患糖尿病者29 636例（95.75%）。多因素Logistic回归分析结果显示，logit（P）（糖尿病患病情况）=-4.632-0.198×（女）+0.864×（年龄45~59岁）+1.684×（年龄≥60岁）+0.635×（高血压）+0.149×（超重）+0.376×（肥胖）-0.531×（偏轻）-0.234×（淋巴细胞百分数偏高）+0.279×（淋巴细胞百分数偏低）+0.304×（红细胞计数异常）-0.430×（红细胞比容偏低）+0.722×（平均红细胞血红蛋白浓度异常）+0.532×（血小板分布宽度异常）+1.016×（癌胚抗原异常）-0.406×（尿酸异常）+1.341×（肌酐偏低）+0.488×（血尿素氮偏高）+0.473×（三酰甘油异常）+0.257×（总胆固醇偏高）+0.544×（高密度脂蛋白偏低）+0.290×（总蛋白异常）+0.395×（丙氨酸氨基转移酶异常）+0.362×（谷氨酰转肽酶异常）+0.993×（阴虚质）+1.016×（气虚质）+0.601×（痰湿质）。模型验证结果显示，训练集ROC曲线下面积（AUC）为0.792，95%CI为0.779~0.816（P<0.05），最佳截断值为0.405，灵敏度为0.771，特异度为0.690；测试集验证准确率达到95.69%，Kappa=0.636（P<0.001）。结论　初步构建了糖尿病风险评估模型，且此模型具有较高诊断效应。中医体质辨识作为重要的影响因素纳入糖尿病发病风险评估的模型中来，可以提高其预测能力，为糖尿病的中医药早期防治提供一定的依据。     

综述三维斑点追踪技术在糖尿病心肌病心功能评价中的应用

糖尿病心肌病(Diabetic Cardiomyopathy,DC)的进展会导致左心室功能减低,因此,早期正确评估左心室功能对糖尿病心肌病患者的治疗和预后有着重要的意义。由于左心室解剖结构的复杂性,常规超声技术通常很难准确的评估左心室功能的变化,三维斑点追踪技术(three-dimensional speckle tracking imaging,3D-STI)是在实时3D超声和斑点追踪技术(STI)基础上发展起来的一项新技术,其对心脏功能的评估不受整个心脏运动方向和运动幅度的限制,能够直观的对心肌各个方向的运动进行追踪。本文首先论述3D-STI 在左心室功能评价中的可行性,再对其在DC左心室功能评价中的研究展开综述。