基质金属蛋白酶2在冠心病猝死心肌中的表达

目的探讨基质金属蛋白酶2（mmp2）在冠心病猝死（SCD）心肌细胞和间质中的表达与SCD的关系。方法选取本教研室2003年51例死亡鉴定病例,分为SCD组,患有冠心病但非SCD组（对照组1）,无严重冠脉粥样硬化（As）病变和其它心血管疾病组（对照组2）,无严重As病变但有其它心脏病组（对照组3）。采用免疫组化SABC法染色及图像分析技术,检测mmp2在各组心肌细胞和间质内表达的阳性率（R值）和平均灰度值（H值）,并比较各组间的差异。结果SCD组与3个对照组之间心肌细胞内romp2H值的差异均有显著性意义;SCD组与对照组2和3之间心肌间质内mmp2H值的差异有显著性意义;镜下各组心肌间质及心肌细胞内表达的阳性率差别明显。结论心肌间质及心肌细胞内mmp2同相表达增高与SCD的发生有密切关系,联合检测心肌和间质mmp2的表达对诊断SCD有重要意义。     

Post mortem molecularly defined familial hypercholesterolemia and sudden cardiac death of young men

Familial hypercholesterolemia (FH) is among the most common single-gene diseases and is due to mutations of the low-density lipoprotein (LDL) receptor gene. In heterozygous FH, serum LDL-cholesterol level is elevated two- to threefold compared to unaffected individuals, men in particular are prone to premature atherosclerosis and early cardiac deaths. However, very little data are available concerning the incidence of premature deaths in FH patients. In Finland two LDL receptor founder mutations cover two-thirds of FH cases, offering a unique possibility to study the potential role of FH in unexpected early cardiac deaths. We studied a total of 149 deceased who had suffered early (< or = 50 years) unexpected cardiac death due to coronary heart disease (CHD). Three individuals (2%) had molecularly defined heterozygous FH, and heterozygous FH was present in two (3%) of the 67 subjects who had demonstrable acute myocardial infarction (AMI). Considering that the two FH mutations cover two-thirds of FH cases in Finland, the overall prevalence of FH underlying early cardiac deaths caused by AMI may be estimated to be in the range 3 to 5%.     

单核细胞趋化蛋白1及其受体在冠心病猝死中的表达

目的：探讨单核细胞趋化蛋白1（monocyte chemotactic protein-1,MCP-1）及其受体CC类趋化蛋白受体2（CC chemokine receptor-2,CCR-2）在冠心病猝死（sudden coronary death,SCD）和非SCD冠状动脉粥样硬化斑块中的差异表达。方法应用免疫组织化学方法检测MCP-1和CCR-2在SCD组、动脉粥样硬化组（冠状动脉粥样硬化但非SCD）、对照组（冠状动脉正常）的差异表达。结果 MCP-1在三组间的阳性细胞表达率分别是78%、47%、0%,两两比较差异均有统计学意义（P＜0.05）;CCR-2在三组间的阳性细胞表达率分别是72%、47%、0%,在SCD组和动脉粥样硬化组、SCD组与对照组表达差异均有统计学意义（P〉0.05）,而在对照组和动脉粥样硬化组差异无统计学意义（P〉0.05）。结论冠状动脉粥样硬化斑块中的MCP-1及其受体CCR-2的表达增加与SCD密切相关。     

遗传性心律失常猝死的分子解剖研究现状及展望

遗传性心律失常所致猝死的死因鉴定是法医病理学领域亟待解决的难题之一。近年来心律失常易感基因/突变的发现和高通量组学技术的推广,使得利用分子遗传学方法筛查猝死的遗传学病因（即＂分子解剖＂）成为可能。本文通过汇总心律失常分子遗传研究的进展,综述传统遗传分析和近期全基因组关联性研究（GWAS）筛查的结果,为心源性猝死的＂分子解剖＂研究提供候选基因列表;并进一步比较针对不明原因猝死所开展的回顾性＂分子解剖＂筛查的结果,探讨新技术在该领域的应用前景。这一综述有助于更好的认识心律失常所致猝死的分子机制,并为借助新一代遗传分析技术进行分子解剖提供有益参考。     

冠状动脉内弹力膜缺损与冠心病猝死的关系

目的探讨冠状动脉内弹力膜(IEL)病变与冠心病猝死(SCD)的关系。方法从本单位近5年尸检案例中挑选60例病例和心脏标本,分为SCD组、对照组A和B组。每例分别在冠状动脉左前降支近段取材,常规制片,HE和双重组合特殊染色,显微镜下观察冠状动脉IEL,并用图像分析技术对特殊染色的IEL进行形态定量分析。结果60例中,SCD组(男性24例,女性6例,年龄30~83岁)的冠状动脉IEL缺失明显(缺失率=41.64%),未缺失的IEL失去原有弯曲度而变平直;对照组A(冠心病非猝死者,男性13例、女性2例,年龄41~80岁)的冠状动脉IEL缺失程度较SCD组稍轻(缺失率=30.53%);对照组B(无冠心病的其他死者,男性8例,女性7例,年龄17~54岁)的冠状动脉IEL仅有轻度缺失(缺失率=15.67%),多保持原有波浪状结构。统计学分析显示,SCD组与对照组、SCD组与对照组B、对照组A与对照组B之间IEL缺损率的差异均具有极显著性意义;SCD组与对照组A在IEL缺损率上的差异有显著性意义。结论SCD与其冠状动脉IEL缺损率的大小密切相关。     

Presence of psychoactive substances in oral fluid from randomly selected drivers in Denmark

The aim of this investigation was to identify and characterise pathogenic mutations in a sudden cardiac death (SCD) cohort suspected of cardiomyopathy in persons aged 0-40 years. The study material for the genetic screening of cardiomyopathies consisted of 41 cases and was selected from the case database at the Institute of Forensic Medicine. Mutational screening by DNA sequencing was performed to detect mutations in DNA samples from deceased persons suspected of suffering from hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricle cardiomyopathy (ARVC). A total of 9 of the examined 41 cases had a rare sequence variant in the MYBPC3, MYH7, LMNA, PKP2 or TMEM43 genes, of which 4 cases (9.8%) were presumed to be pathogenic mutations. The presumed pathogenic mutations were distributed with one case of suspected HCM and DCM (MYH7; p.R442H), one case of suspected DCM (LMNA; p.R471H), and two cases of suspected ARVC (PKP2; p.R79X and LMNA; p.R644C). The presented data adds important information on the genetic elements of SCD in the young, and calls for expert pathological evaluation and molecular autopsy in the post-mortem examination of SCD victims with structural anomalies of the heart.     

The earlobe crease, coronary artery disease, and sudden cardiac death: an autopsy study of 520 individuals

The majority of previous studies have demonstrated a correlation between diagonal earlobe creases (ELC) and coronary artery disease (CAD).In this study of 520 forensic autopsy cases, the earlobes were studied and photographed before autopsy, and the existence of a diagonal ELC was noted in 55%. The cause of death, the degree of coronary atherosclerosis, aortosclerosis, and cerebrosclerosis, as well as heart, kidney, and spleen weights, were noted in each case. The body mass index (BMI), thickness of abdominal fat, baldness, and excessive hair in the meatus externa of the external ears were also assessed. Nonparametric methods were used in the statistical calculations.It was found that ELC was strongly correlated with CAD in both men and women (P < 0.0001) but with sudden cardiac death (SCD) only in men (P < 0.04). The sensitivity of the ELC sign was 75% and the positive predictive value (ppv) was 68%. In individuals below 40 years, the ppv was as high as 80%. Using multiple logistic regression analysis, ELC was found to be the strongest independent risk factor for CAD and SCD apart from age and BMI (both genders), as well as baldness and hair in the meatus externa (in males).It is concluded that in a patient population similar to that in the present study the ELC sign could be especially useful in screening for premature CAD in younger individuals.     

A pathological study of sudden coronary death in China: report of 89 autopsy cases.

This paper reports the results of a forensic pathological study of 89 autopsy cases of Sudden Coronary Death (SCD). Of 89 cases, 63 (52 male, 11 female) were narrowed by 76-100% in cross-sectional area (XSA) of the coronary artery (CA) and 26 (22 male, 4 female), by 51-75%. Atherosclerotic plaques in the CA were serious and extensive, especially in the left anterior descending and often involved several branches of CA at the same time. Recent thrombosis was found in 18 cases, haemorrhage in plaques in 17 cases. Only 2 cases had visible acute myocardial infarction. Inflammatory cell infiltration was found in coronary plaques in 36 cases. Myocardial fibrosis or small scar formation was detected in 51 cases. It is suggested that although the incidence of coronary heart disease (CHD) is low in China, SCD is the commonest mode of Sudden Unexpected Death. The majority of SCD (52%) were middle aged males (30-49 years old). Most of the cases died suddenly during sleep without any clear precipitating factors. The characteristics of occurrence and pathological changes in the CA and myocardium and the pathological diagnosis of SCD are also analysed and discussed.     

冠心病猝死冠脉斑块组成成分的病理形态学改变

目的探讨冠心病猝死(SCD)组和对照组冠脉粥样硬化斑块纤维帽厚度和脂质核心百分比的差异。方法随机挑选病例及心脏标本共64例,分为SCD组和对照组。在冠脉粥样硬化最严重的部位取材,制片,并行HE染色,显微镜观察冠脉的病理变化和斑块的组成,采用图像分析系统对冠脉斑块纤维帽厚度和脂质核心与整个斑块的百分比进行定量分析,所得数据用SPSS11.5统计软件进行数据分析。结果SCD组中,冠脉粥样硬化病变Ⅳ级21例,Ⅲ级15例,对照组中冠脉粥样硬化病变Ⅳ级12例,Ⅲ级16例,两组在病变的严重程度上未见显著性差异(P>0.05);两组冠脉粥样硬化斑块纤维帽的厚度和脂质核心百分比均有显著性差异(P<0.01)。结论SCD组与对照组在冠脉粥样斑块的纤维帽厚度和脂质核心百分比大小等两方面均存在显著性差异;对SCD的病理诊断和法医学鉴定都具有重要意义。     

178例心源性猝死法医组织病理学诊断分析

目的探讨心源性猝死(SCD)的病理特点与鉴别要点。方法对四川华西法医学鉴定中心2000—2005年尸检出的178例SCD死亡案例进行回顾性分析,主要对其病因、年龄、诱因及病理改变进行分析。结果本组资料显示冠心病、心传导系统病变、心肌炎、心肌病等在SCD中占有较大比例。冠心病猝死是中老年人SCD的最主要原因,青壮年人SCD的病因以非冠心病为主。如传导系统病变、心肌炎、心肌病。在儿童的SCD中先天性心脏病、传导系统病变及心肌炎占主导地位。结论不同的病因,其病理特点不同,其病理变化是法医学鉴定的主要依据。     

犬11个STR基因座的遗传多态性

目的调查犬11个STR基因座的群体遗传多态性。方法应用自主构建的犬11个STR基因座（PEZ1、PEZ2、PEZ3、PEZ5、PEZ6、PEZ8、PEZ12、FH2010、FH2054、FH2132和FH2611）荧光复合扩增体系，扩增105只犬的样本，统计各基因座扩增结果，并分析其群体遗传参数。结果11个STR基因座的累积非父排除率和累积个体识别率分别为0．9330621和0．9999999．平均杂和度和平均多态信息含量分别为0．502和0．640。结论该11个犬STR基因座的遗传多态性较好，可以有效用于犬的个体识别和亲权鉴定。     

97例心性猝死的法医病理学分析

目的探讨心性猝死（SCD）的特点、病理基础及致死因素和诱因等。方法对本系2002年12月至2006年12月期间，所作450例法医病理检案的97例心性猝死案例进行分析研究。结果97例SCD患者中，冠心痛猝死38例，心肌炎23例，心肌痛16例，高血压性心脏病12例，主动脉瘤破裂4例，肺栓塞4例。结论SCD病程短骤、凶险，以老年男性多见，冠心病占首位。由于猝死的因素繁多，因此对猝死事件的法医学鉴定要根据其发生特征和变化规律，作出客观、全面、准确的签定结论。     

KCNE、KCNQ1与心性猝死的相关性研究进展

部分心性猝死由于缺乏明确的病理学改变,其鉴定工作一直是法医工作者的一大难题。近年来,与长QT综合征、心房颤动等致死性心律失常疾病相关基因（KCNE基因家族与KCNQl）等研究逐渐增多。国内外研究发现KCNE和KCNQ1基因编码心肌钾离子通道,其基因异常可引起严重的心律失常,甚至导致心性猝死。因此,死后KCNE和KCNQl的基因检测对于心性猝死鉴定具有重要意义。本文对KCNE、KCNQl与心性猝死的相关性研究进展进行综述,希望能为法医学研究和实践提供参考。     

冠状动脉粥样斑块中C-反应蛋白的免疫组化研究

目的探讨冠状动脉粥样硬化斑块中C-反应蛋白(CRP)对冠心病猝死(SCD)的诊断意义。方法从本教研室2001~2004年尸检案例中挑选68例案例资料和心脏标本,分为3组A组SCD(27例);B组冠心病非猝死者(21例);C组无明显动脉粥样硬化病变的死者(20例);应用免疫组化染色(SABC法)和图像分析技术,检测每例冠状动脉左前降支和右主支粥样硬化斑块内的CRP染色情况,并对所得数据进行统计分析。结果A组有20例CRP免疫组化染色强阳性,6例呈较强阳性,1例为弱阳性;B组中3例呈较弱阳性,11例微弱阳性,7例为阴性;C组均未见阳性反应。结论检测冠状动脉粥样硬化斑块中的CRP对SCD的死后诊断具有一定意义。     

生物化学指标检测在心源性猝死法医鉴定中的应用

早期缺血性心肌病变引起的心源性猝死（sudden cardiac death,SCD）由于发病突然,常缺乏典型的形态学改变和临床表现,易被怀疑为刑事案件,查明其死亡原因对法医学实践有指导作用。本文对国内外有关无机离子、肌酸激酶、肌钙蛋白、心房利钠尿肽、脑利钠尿肽等生物化学指标检测在诊断SCD方面的研究进展加以综述,以期为SCD的法医学诊断提供参考。     

窦房结间质增生与年龄及右冠状动脉病变程度的关系

目的研究年龄及右冠状动脉粥样硬化病变程度对窦房结间质增生的影响。方法选择右冠状动脉有粥样硬化病变的心脏标本,登记年龄,复查并登记右冠状动脉病变,窦房结取材,常规制片,HE染色及Massom三色染色,用图像分析系统分析窦房结间质增生程度及右冠状动脉粥样硬化斑块病变的阻塞程度。结果右冠状动脉粥样硬化病变程度及年龄对窦房结间质增生的影响都有统计学意义(P0.001);右冠状动脉粥样硬化病变程度对窦房结间质增生的影响强度约为年龄的2.16倍。结论年龄及右冠状动脉粥样硬化病变程度均与窦房结间质增生有线性关系,右冠状动脉粥样硬化病变程度导致窦房结间质增生较年龄因素更为明显。     

Study by next generation sequencing of sudden cardiac death (SCD)

Sudden cardiac death (SCD) is one of the most common causes of death; most SCD are related to secondary arrhythmias, to structural heart disease, or to primary electrical abnormalities of the heart.A significant number of SCD, especially among young people, are due to genetic heart disorders, both with structural and arrhythmogenic abnormalities. However SCD occurs also in patients with negative clinical history, autopsy is not always conclusive for a diagnosis.Recent technological advances in DNA sequencing, have led to the commercialization of genetic testing now widely available in clinical practice. In particular, next generation sequencing, allows the large-scale and rapid assessment of entire genomes.Analysis of SCD with a NGS panel of 174 genes was performed in our laboratory in order to identify the genetic causes and thus to direct the clinician to an accurate clinical and genetic screening of relatives.Two SDC were studied:Case 1: female, 57, without story of syncope and no previously highlighted cardiac alteration, died post cardiac arrest; negative family history. Autopsy was apparently negative.Case 2: male, 52, who died during a football game; negative family history, neurological episodes occurred before death was reported by close relative. Autopsy was positive for ventricular hypertrophic.In both cases we made a genetic diagnosis.     

常用心脏标志物的生化检测及法医学应用

在法医病理学鉴定工作中,由早期缺血性心肌病变及致死性心律失常引起的心源性猝死常常缺乏典型的病理组织学改变,如何准确、客观地诊断、查明死因是法医病理学亟待解决的问题。近来研究发现的一些心肌特异性指标对心源性猝死的诊断有很好的应用前景。本文介绍几种常见心肌特异性标志物的生化特点、实验室检验方法以及临床和法医学应用前景,以期为心源性猝死的法医病理学鉴定提供依据。     

Impact of Myocardial Infarction and Abnormalities of Cardiac Conduction System on Sudden Cardiac DeathCSCD

Sudden cardiac death (SCD), most commonly seen in coronary heart disease, is a kind of sudden death caused by series of cardiac parameters, which usually combines with myocardial infarction. However, some SCDs (including early myocardial infarction) happen suddenly and cause death in a very short time. In these circumstances, typical morphological changes are lack in macroscopic or microscopic fields, which make such SCDs become the emphasis and difficulty in the present research. SCD caused by myocardial infarction and abnormalities of cardiac conduction system (CCS) is related to atherosclerosis of coronary artery closely. This paper reviews cardiac dysfunction caused by myocardial infarction and diseases of CCS from morphology and molecular biology, and explores potential relationship between them. This paper aims to provide clues to the mechanism of myocardial infarction related sudden death and possible assistance for forensic diagnosis of SCD. © 2017 by the Editorial Department of Journal of Forensic Medicine.