偏头痛的遗传学研究进展

偏头痛是一种常见的神经血管紊乱疾病,其发病机制还不十分清楚,遗传因素和环境因素共同作用促使其发生。偏头痛的遗传学机制目前研究还不透彻,唯一定论的是符合孟德尔遗传的家族性偏瘫型偏头痛(familial hemiplegic migraine,FHM),此外还有很多离子通道基因、神经系统相关基因、血管基因以及激素相关基因与偏头痛易感性有关,但这些候选基因是否属于偏头痛的致病基因还需要大量实验验证。表观遗传学在偏头痛发病机制中可能发挥一定的作用,其研究还处于起步阶段。     

先天性巨结肠病因学研究进展

先天性巨结肠（Himchsprung病，HD）又称肠无神经节细胞症，为小儿常见疾病之一，发病率居先天性消化道畸形第二位。尽管对HD的病因学研究已经有近百年的历史，但至今尚未完全清楚．对该病病因和发病机制的研究仍然是国内外学者的热门话题。近年，随着新技术、新方法的不断应用，尤其是随着分子遗传学的发展，人们对HD的发病机制有了更深入的认识。目前较一致的观点是：HD是具有多基因遗传特性的先天性发育畸形，胚胎早期阶段微环境改变及遗传学因素在巨结肠发病中起重要作用，即由遗传和环境因素共同作用所致：此外，病毒感染、肠壁缺血等因素也参与该病的发生。本文就HD病因学研究进展作一综述。     

唐氏综合征合并先天性心脏病相关基因的研究进展

唐氏综合征(Down syndrome,DS)是由21-三体引起的一种遗传综合征。约50%的DS患儿合并不同类型的先天性心脏病(congenital heart disease,CHD),其发病机制尚未阐明。目前已知的在DS合并CHD的发病中起关键作用的基因包括DSCAM(Down syndrome cell adhesion molecule)、RCAN1(regulator of calcineurin 1)、COL6 A1～2(collagen typeⅥalpha 1-2chain)、CRELD1(cysteine rich with EGF like domains 1)、ALK2(activin-like kinase 2)及KCNJ6(potassium voltage-gated channel subfamily J member 6)。以上基因的致病机制主要涉及两种假说,即基因剂量效应假说和基因突变假说。本文主要阐述DS合并CHD相关基因的作用机制及其相应的先心病类型,为DS合并CHD的病因学研究提供参考。     

先天性心脏病患儿V1导联T波直立与心脏彩色多普勒超声对比分析

先天性心脏病（congenital heart disease,CHD）是临床上常见的一种新生儿血管畸形疾病,先天性心脏病发病机制复杂,大多数受遗传因素和周围环境综合作用引起［1］。CHD是新生儿死亡的主要危险因素。随着彩色多普勒超声诊断技术的发展和成熟,已成为临床上诊断先天性心脏病的主要方法之一［2］,而心电图作为一种简便易行的检查方法,对于CHD的早期诊断价值仍不容忽视。为此,本文对比分析CHD患儿V1导联T波直立心电图与心脏彩色多普勒超声的表现,旨在探讨心电图对先天性心脏病的诊断价值。     

系统性红斑狼疮致病基因研究进展

系统性红斑狼疮(SLE)是一种累及多脏器的自身免疫性疾病,多发于育龄女性,其发病与遗传、内分泌及感染等多种因素相关。其中,遗传因素近年来被众多学者所关注,SLE是一种多基因遗传性疾病这个观点获得了学者们的认可。随着基因检测技术的不断进步,目前已确定多种SLE强关联基因,此外,许多目前作用未知的相关基因也逐渐被发现。本文通过对固有免疫应答和适应性免疫应答中的不同信号通路分子进行研究,综述目前SLE相关致病基因的研究进展,以期为SLE多效基因综合致病因素研究提供依据。     

高甘油三酯血症与冠心病的关系

高胆固醇血症早以确认是冠心病 (CHD)的独立危险因子。而对于血清甘油三酯 (TG)增高是否增加 CHD的危险性。至今尚有争议 [1 ]。近年来许多研究者试图明确高 TG血症与动脉粥样硬化 (AS)和 CHD之间的关系及致病的机制。本文就高 TG血症与冠心病之间的有关问题进行探讨 ,从中进一步了解它们之间的关系。1　高 TG血症与 CHD的流行病学研究CHD是遗传、环境和个体等多种因素所致的疾病。在过去的几十年临床研究中 ,人们普遍认为多种因素与之有关。其中吸烟、高血压及高胆固醇血症为几个重要因素。而对于高 TG血症是否是 CHD的独立危…     

先天性巨结肠的研究进展

先天性巨结肠（hirschsprung’s disease,HD）是小儿常见的先天性胃肠道疾病,为神经脊细胞源性疾病和多基因遗传病。其病因和发病机制尚不明确,有着广阔的探究前景。近年来HD遗传基础、致病机制等被逐渐探究,其临床分型和诊断标准逐渐明确,诊断方法及治疗技术不断精进。本研究对国内外具有代表性的关于HD的遗传基础、致病机制、临床诊断、临床治疗、遗传咨询、产前诊断和预防等方面的研究进行总结,以期提高对先天性巨结肠的认知,为进一步深入研究HD提供理论参考和借鉴。     

帕金森病病因的分子遗传学研究进展

自詹姆斯·帕金森在1817年首次描述帕金森病以来,遗传因素在贩金森病发生过程中的作用一直存在争议。人们曾一度认为帕金森病主要受环境影响,直到1996年Polymeropoulos等在一个意大利家族中发现了致病基因α-synuclein,继之以有科学家在日本发现另一致病基因Parkin,从此,遗传因素在帕金森病发病中所起作用得到肯定。目前,人们普遍认为帕金森病的发生是环境因素和遗传因素共同作用的结果。那么,帕金森病的遗传学基础窨是怎样的呢?就可能与帕金森病遗传易患性有关的基因作一综述。     

人白细胞抗原DRB1和DQB1等位基因多态性与冠心病的相关性研究

动脉粥样硬化是冠心病(CHD)的主要病因，但对其发生机制不清。目前，人白细胞抗原(HLA)的Ⅱ类抗原DR基因位点(HLA-DRB1)和DQ基因位点(HLA-DQB1)与CHD相关性的研究国内则鲜见报道。本研究用顺序特异引物聚合酶链反应(PCR-SSP)及等位基因序列分析技术，研究黑龙江汉族人2个等位基因与CHD的相关性，并为探讨CHD的发病机理提供遗传学依据。     

扩张型心肌病基因型-环境-表型研究进展

扩张型心肌病(DCM)是一组表现为单侧或双侧心腔扩大伴收缩功能障碍的异质性疾病。DCM可归因于遗传和非遗传原因，目前已有40多个致病基因相继被报道，其中包括编码肌小节、细胞骨架蛋白、离子通道、线粒体、桥粒等相关基因。近年来，在致病基因的发病机制方面取得了很大进展，也逐渐认知到环境、非编码RNA、DNA甲基化、组蛋白乙酰化修饰等对该病表型的影响，虽然其基因型和表型的关系仍未完全阐明，从基因组-环境-表型的模式对DCM的分子机制的探讨使我们对DCM有了更深层次的理解，本文将对DCM的遗传学基础、发病机制以及调控机制进行综述。     

Interventional and surgical treatment of cardiac arrhythmias in adults with congenital heart disease

Arrhythmias are a major cause of morbidity, mortality and hospital admission in adults with congenital heart disease (CHD). The etiology of arrhythmias in this population is often multifactorial and includes electrical disturbances as part of the underlying defect, surgical intervention or hemodynamic abnormalities. Despite the numerous existing arrhythmia management tools including drug therapy, pacing and ablation, management of arrhythmias in adults with CHD remains difficult and challenging. Owing to improvement in mapping and ablation techniques, ablation and arrhythmia surgery are being performed more frequently in adults with CHD. However, there is little information on the long-term results of these treatment strategies. The purpose of this article is therefore to review the available data on nonpharmacological treatment of cardiac arrhythmias in adult patients with CHD and to give an overview of the available data on the early and late outcomes of these treatment strategies.     

Interventional and surgical treatment of cardiac arrhythmias in adults with congenital heart disease

Arrhythmias are a major cause of morbidity, mortality and hospital admission in adults with congenital heart disease (CHD). The etiology of arrhythmias in this population is often multifactorial and includes electrical disturbances as part of the underlying defect, surgical intervention or hemodynamic abnormalities. Despite the numerous existing arrhythmia management tools including drug therapy, pacing and ablation, management of arrhythmias in adults with CHD remains difficult and challenging. Owing to improvement in mapping and ablation techniques, ablation and arrhythmia surgery are being performed more frequently in adults with CHD. However, there is little information on the long-term results of these treatment strategies. The purpose of this article is therefore to review the available data on nonpharmacological treatment of cardiac arrhythmias in adult patients with CHD and to give an overview of the available data on the early and late outcomes of these treatment strategies.     

The genetic epidemiology of neurodegenerative disease

Gene defects play a major role in the pathogenesis of degenerative disorders of the nervous system. In fact, it has been the very knowledge gained from genetic studies that has allowed the elucidation of the molecular mechanisms underlying the etiology and pathogenesis of many neurodegenerative disorders. In this review, we discuss the current status of genetic epidemiology of the most common neurodegenerative diseases: Alzheimer disease, Parkinson disease, Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington disease, and prion diseases, with a particular focus on similarities and differences among these syndromes.     

Immunotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, with over a million new cases annually. It is generally advanced upon detection due to underlying liver disease, which further complicates treatment. Most of the therapeutic strategies in current use (surgery, transplantation, irradiation or chemotherapy) are either palliative or only of benefit to a small percentage of patients. This article reviews the biology of HCC, including many of the molecular changes and mechanisms leading to HCC development. This article discusses the recent innovative strategies to interfere with the progression of HCC, including novel gene therapy strategies. The most recent data supporting the use of immunotherapy for hepatocellular cancer is reviewed in detail.     

Immunotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, with over a million new cases annually. It is generally advanced upon detection due to underlying liver disease, which further complicates treatment. Most of the therapeutic strategies in current use (surgery, transplantation, irradiation or chemotherapy) are either palliative or only of benefit to a small percentage of patients. This article reviews the biology of HCC, including many of the molecular changes and mechanisms leading to HCC development. This article discusses the recent innovative strategies to interfere with the progression of HCC, including novel gene therapy strategies. The most recent data supporting the use of immunotherapy for hepatocellular cancer is reviewed in detail.     

Pain of urogenital origin

Chronic nonmalignant pain syndromes (longer than 6 months duration) of urogenital origin are well described but poorly understood focal pain syndromes. Pain in these areas of the body is usually very embarrassing for the male and female patient, who may be afraid to discuss his or her symptoms with family members, friends, and health care providers. Except in those cases in which a specific secondary cause can be identified, the etiology of chronic urogenital pain often remains unknown. Currently available treatment options are empirical only. Although cures are uncommon, some pain relief can be provided to almost all patients using currently available treatment strategies. Better knowledge of the underlying pathophysiologic mechanisms of chronic urogenital pain is needed to develop treatment strategies specifically targeted against the underlying mechanisms.     

Relationship between non-alcoholic fatty liver disease and coronary heart disease

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease and considered a liver manifestation of metabolic syndrome. It is in close relationship with insulin resistance, obesity, diabetes mellitus, all of which increase risk of cardiovascular disease (CVD). Besides, many studies point out that NAFLD independently contributes to the development of atherosclerosis and CHD. On the other hand, CVDs are the leading cause of death in NAFLD patients. Many pathophysiological changes and molecular mechanisms play an important role in NAFLD for CVD formation. Atherosclerosis is common in NAFLD, which also mainly contributes to the CVD formation and CHD. Many studies linking atherosclerotic CHD and NAFLD are present in the literature. Subclinical CHD, mainly detected by coronary computed tomography views, have been detected more common in NAFLD patients. Presence of NAFLD has been found to be more common in patients with severe CHD and in stable CHD, NAFLD has been found to be associated with more diffuse disease. In acute coronary syndromes, especially in acute myocardial infarction, patients with NAFLD have been found to have poor prognosis when compared with NAFLD free patients. In this review, our aim is to evaluate the relationship between NAFLD and CHD in detail and go over the pathophysiological mechanisms underlying this relationship.     

Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines

Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation.