右位心形成相关分子机制及调控

右位心的形成主要与胚胎心脏左-右体轴的不对称发育异常有关.Nodal、Pitx2、Cited2等基因的不对称表达是脊椎动物左-右体轴不对称分化的重要影响因子,其表达异常会导致器官左右不对称分化异常,表现为右位心、中位心、异位心及其他内脏异位.右位心常伴有多种类型的先天性心脏结构畸形,治疗难度大,预后不良.深入研究右位心形成的影响因素及分子机制,旨在进一步探索右位心的基因诊断及早期干预措施,以提高患者的成活率和生存质量.该文对右位心形成的分子机制及其调控机理进行综述.     

支气管哮喘相关基因的研究进展

支气管哮喘(哮喘)是一种复杂的多基因疾病,由环境因素和遗传因素共同作用所致.哮喘基因的研究策略主要有:定位克隆法、候选基因法及全基因组关联研究,连锁分析和关联分析是两种主要分析策略.该文从功能学角度分类讨论近年来发现的哮喘易患基因:Toll样受体基因、白细胞介素-13基因、程序性细胞死亡-4基因、趋化因子-5基因、瞬时受体电位通道-1基因、大脑衍生神经生长因子基因.     

儿童白血病基因表达谱研究进展

随着人类基因组计划全部核苷酸测序的完成,人们可以通过对全基因组的分析来了解个体在不同生长发育阶段或不同生理状态下的大量基因信息和相应生物功能.由此应运而生的基因芯片技术以其无可比拟的信息量、高通量、快速、准确地分析基因的本领,已被广泛用于生物研究领域,在人类重大疾病,如癌症的发病机制、诊断、治疗、药物开发等方面也发挥了巨大的作用.     

基因拷贝数变异与先天性心脏病的研究进展

基因拷贝数变异是指与参考基因组相比,长度在1 kb以上的DNA片段缺失、插入、重复和复杂多位点的变异.基因拷贝数变异存在于人类和其他哺乳动物基因组中,与包括先天性心脏病在内的一系列复杂遗传性疾病相关.基因拷贝数变异是目前的研究热点之一.该文就基因拷贝数变异的概念、检测方法、在先天性心脏病领域进展作一综述.     

hsa-miR-17-92 cluster及其同源体靶基因的生物信息学分析

目的 对hsa-miR-17-92 cluster及其同源体进行系统的生物信息学分析,预测其可能参与的生物学过程,为深入研究其在脂肪细胞分化、肥胖发生等过程中的功能与机制奠定基础.方法 1.应用PubMed、Google等信息搜索工具查找hsa-miR-17-92 cluster及其同源体的所有研究,综述已有研究进展;2.应用miRBase获取hsa-miR-17-92 cluster及其同源体的各成员序列,并分析其序列特征及保守性;3.应用美国国家生物技术信息中心(NCBI) blast、NCBI mapviewer、基因组生物信息学(UCSC) Browser工具分析hsa-miR-17-92 cluster及其同源体所在基因组的序列特征;4.应用TargetScan5.1,PicTar及miRanda预测hsa-miR-17-92 cluster及其同源体靶基因,取三者预测结果的交集,进一步进行功能注释和Pathway富集分析.结果 1.现有研究提示hsa-miR-17-92 cluster及其同源体在脂肪细胞分化、肿瘤疾病、心脏及肺发育、免疫系统与血管形成等生物学过程中有重要作用;2.hsa-miR-17-92 cluster及其同源体进化上高度保守,根据种子序列同源性可分为4类,且在多物种间非常保守;3.hsa-miR-17-92 cluster及其同源体预测靶基因的功能与细胞周期、细胞黏附、Wnt、TGF-β信号、p53、丝裂原活化蛋白激酶等信号通路有较大的相关性,可能参与了前列腺癌、胰腺癌、结肠癌等多种疾病通路.结论 通过对hsa-miR-17-92 cluster及其同源体系统的生物信息学分析,初步阐明了hsa-miR-17-92 cluster及其同源体的基本生物学特征,并为hsa-miR-17-92 cluster后续研究提供了功能与机制的线索.     

肠道菌群与肥胖的关联性研究现状

当今社会,肥胖已经成为一个世界范围内的社会和健康问题,其发病机制普遍认为是由遗传与环境因素共同介导.有学者利用人类全基因组关联研究发现,胰岛素诱导基因2、体脂量和肥胖症相关基因、黑皮质素-4-受体基因等基因与体质指数(BMI)密切相关.但这些基因中有些具体功能还未揭示清楚,有些存在着种族差异及遗传异质性等问题.近年的研究发现环境因素中肠道菌群与肥胖的发病有一定的相关性.众所周知,肠道菌群具有特异的代谢效能,为宿主分解营养物质,提供能量底物.近年有学者研究认为肠道菌群中拟杆菌门/硬壁菌门的比例失调在肥胖的发生发展中有重要作用.该文就当前国内外相关肠道菌群与肥胖的关联性研究作一综述.     

人巨细胞病毒UL/b’区基因编码蛋白生物学功能的研究进展

人巨细胞病毒(human cytomegalovirus,HCMV)在人群中感染广泛,不仅是免疫抑制患者的严重致病原,也是引起新生儿先天及围生期感染最常见、危害最大的一种病原体.近年来,针对区别于实验室株的一个特殊区域UL/b’区基因编码蛋白生物学功能的研究是国内外HCMV研究领域的一个热点.目前已经发现该区域基因产物在HCMV的毒力、传播、组织细胞嗜性及免疫逃避等方面发挥重要作用,其中的UL133-UL138位点可能促进HCMV潜伏感染的建立和维持,而pUL138是目前病毒基因组中鉴定出的惟一明确与HCMV潜伏感染相关的决定因子.因此,HCMV UL/b’区基因产物在HCMV感染过程中发挥重要作用.该文就HCMV UL/b’区部分基因,尤其是与HCMV潜伏感染相关的UL138基因结构及其编码蛋白生物学功能进行综述,为阐明HCMV感染致病机制奠定基础.     

非综合征型唇腭裂易感基因位点研究进展

非综合征型唇腭裂是一种常见的出生缺陷,病因复杂,目前普遍认为是遗传因素和环境因素共同作用的结果.先天性唇腭裂易感基因是自全基因组测序以来的研究热点,筛选出的众多候选基因正不断被基因位点多态性检测、病例对照研究、Meta分析等方法验证,但结果迥异.该文就近年来研究较多的非综合征型唇腭裂易感基因以及环境因素与唇腭裂相互关系方面的研究进展展开综述.     

哮喘易感基因的研究进展

支气管哮喘(哮喘)是一种多基因遗传病,由易感基因和环境因素共同作用而发病.通过候选基因法、定位克隆法和全基因组关联研究共确定了数百个哮喘易感基因,主要包括β2肾上腺素能受体基因、白细胞介素4受体基因、微丝蛋白基因、心房利钠素前体A基因、Ⅰ型肌醇多聚磷酸4磷酸酶基因、解整合素.金属蛋白酶33基因、双肽酶10基因、视蛋白3基因、血清类黏蛋白1样蛋白3基因、磷酸二酯酶4D基因、几丁质酶3类1基因等,其中多个基因在独立人群中得到验证.     

新生儿瓜氨酸血症Ⅰ型一例ASS1基因突变研究北大核心CSCD

目的 对1例瓜氨酸血症Ⅰ型家系进行基因检测,阐明其病因,为该病的诊断和遗传咨询提供依据.方法 提取患儿及其父母外周血基因组DNA,采用Sanger测序对ASS1基因14个外显子进行DNA测序,Phyre软件分析ASS1蛋白分子的三级结构及功能.结果 检测到患儿有c.951delT （F317LfsX375）和c.1087C ＞T （R363W）两个杂合突变,分别遗传自父亲和母亲.蛋白质结构分析发现,c.951 delT影响ASS1蛋白分子的空间结构和功能.结论 ASS1基因c.951 delT和c.1087C＞T复合杂合突变是导致患儿瓜氨酸血症Ⅰ型的分子病因,c.951 delT为未见报道的突变类型,推测其改变了蛋白质分子的空间构型,从而影响ASS1蛋白的酶活性.     

46例重型肺炎心功能检测及分析

为观察重型肺炎患儿的心功能情况 ,用彩色多谱勒超声心动图测定26例重型肺炎无器质性心脏病患儿、20例重型肺炎合并器质性心脏病患儿、20例轻型肺炎患儿和30例正常健康小儿的左室收缩功能、舒张功能及右室血流参数 ,同时检查血气分析、胸片、心电图及心肌酶谱。结果显示:26例重型肺炎无器质性心脏病者的左室收缩、舒张功能及右室血流参数与一般肺炎组及正常对照组比较差异无显著性(P>0.05) ,同期测定的心胸比例、心电图正常 ,心肌酶谱基本正常 ,仅有8例AST或LDH轻度升高 ;20例重型肺炎合并器质性心脏病者 ,左室收缩功能、舒张功能及右室血流参数与肺炎组及正常对照组比较 ,差异有显著性 (P<0.01 ,P<0.05)。提示肺炎患儿若未合并器质性心脏病者 ,不易引起心衰     

Symptomatic heart disease in infants: Comparison of three studies performed during 1969–1987

We compare the data of three studies of hospitalized infants with cardiac disease performed between 1967 and 1987. The studies were from the New England Regional Infant Cardiac Program (1967–1974), the Brompton Hospital (1973–1982), and the Northern Great Plains Regional Cardiac Program (1982–1987). Considering differences in classification among the studies, the distribution of cardiac anomalies during the first year of life is similar among the three studies. Although about 30% of infants are admitted during the first week of life and nearly 40% between 3 and 6 months, the proportion of infants admitted between 6 and 12 months was larger (25%) in the latest than in the earliest study (10%). There were also differences in the distribution of the diagnoses at various ages, reflecting changes in the patterns of care during the three eras.     

Atrial septal defect in Malta

OBJECTIVE: To study diagnostic and surgical trends in atrial septal defect (ASD) in a population-based study, and estimate birth prevalence and spontaneous closure rates. METHODOLOGY: All patients in Malta diagnosed as having ASD and born between 1990 and 1994 were identified from various sources. This took place in the setting of a regional hospital supplying diagnostic services for the entire population. Echocardiographic follow-up was also undertaken for lesions not requiring intervention. RESULTS: A total of 190 patients born in this period were diagnosed as having ASD. Age at diagnosis and age at surgery have decreased significantly over the period under study (P < 0.0001). The mode of diagnosis has become entirely noninvasive, and the perioperative mortality decreased dramatically over time. For the period 1990-94, the incidence at birth for defects not requiring intervention was 2.0/1000 live births, defects requiring intervention 0.4/1000 live births. A total of 92% of 50 defects not requiring intervention closed spontaneously, and the remainder had spontaneously decreased in size on follow-up. CONCLUSIONS: ASD is a relatively benign malformation in which early and noninvasive diagnosis can be achieved, with an extremely low interventional mortality.     

Low donor‐to‐recipient weight ratio does not negatively impact survival of pediatric heart transplant patients

Tang L, Du W, Delius RE, L’Ecuyer TJ, Zilberman MV. Low donor‐to‐recipient weight ratio does not negatively impact survival of pediatric heart transplant patients.
Pediatr Transplantation 2010: 14:741–745. © 2010 John Wiley & Sons A/S. Abstract: A major limitation to success in pediatric heart transplantation is donor organ shortage. While the use of allografts from donors larger than the recipient is accepted, the use of undersized donor grafts is generally discouraged. Using the UNOS database, we wanted to evaluate whether using smaller donor hearts affects the short‐ and long‐term survival of pediatric heart transplant patients. A retrospective analysis of data entered into the UNOS database from April 1994 to May 2008 was performed. Pediatric heart transplant recipients (ages 0–18 yr) with DRWR <2.0 were identified and divided into two groups: Low‐DRWR (<0.8) and Ideal‐DRWR (0.8–2.0). Patients’ demographics, pretransplant diagnoses, age at transplantation, severity of pretransplant condition, and rate of complications prior to hospital discharge after transplantation were noted. Fisher’s exact, chi‐square, and Wilcoxon rank sum tests were used to compare patients’ baseline characteristics. Kaplan–Meier curves and Cox proportional hazard regression were used to compare patients’ survival and to identify independent risk factors for outcomes. There were 3048 patients (204 with Low‐ and 2844 with Ideal‐DRWR). The Low‐ratio group patients were older (8.3 vs. 6.9 yr; p = 0.001), there was a slight male predominance in the Low‐DRWR group (p = 0.055). The Low‐DRWR group had longer transplant wait time than the Ideal‐DRWR group (97 vs. 85 days; p = 0.04). The groups did not differ in race, primary diagnoses, severity of pretransplant condition (medical urgency status, need for ventilation, inotropic support, ECMO, nitric oxide, or dialysis, the PVR for those with bi‐ventricular anatomy), or post‐transplant complications (length of stay, need for inotropic support, dialysis, and rate of infections). The Low‐DRWR patients had less episodes of acute rejection during the first‐post‐transplant month. Infants with DRWR 0.5–0.59 had lower 30‐day survival rate (p = 0.045). There was no difference in short‐ and long‐term survival between the patients with DRWR 0.6–0.79 and DRWR 0.8–2.0. Use of smaller allografts (DRWR 0.6–0.8) has no negative impact on the short‐ and long‐term survival of pediatric heart transplant patients.     

Evaluation of a child with suspected congenital heart disease

Congenital heart disease (CHD) is the most common congenital malformation in the United Kingdom (UK). Despite major advances in diagnosis and management over the last decade, CHD remains a leading cause of infant morbidity and mortality. Current existing screening tools fail to identify up to 39–50% of children with CHD before discharge from hospital. Pulse oximetry screening has been well studied and seems a promising screening tool. Combined use of pulse oximetry with fetal anomaly screening and routine newborn examination potentially could detect up to 75–92% of critical CHDs in asymptomatic infants. Notably pulse oximetry screening has yet to be incorporated as part of universal screening programme in the United Kingdom. Echocardiography remains the gold standard investigation but may not be always available. A detailed history and thorough clinical examination are of paramount significance in suspected CHD in infants. As the clinical presentation can mimic or overlap with other common conditions in infancy (sepsis, respiratory or metabolic condition), a high index of suspicion with a systematic approach is vital for the timely diagnosis and management.     

CONGENITALLY CORRECTED TRANSPOSITION OF THE GREAT ARTERIES A Clinical Study of 101 Cases

ABSTRACT. The anatomy, natural history, clinical features and symptomatology of 101 cases of congenitally corrected transposition of the great arteries (C-TGA) diagnosed over a 20-year period at Hospital for Sick Children, Toronto, Ontario, is reported. Only 1 patient had no associated lesion and only 14 an intact ventricular septum. Pulmonary stenosis was present in a little more than half of the patients. Left A-V valve involvement existed in 21 patients. In spite of the hich incidence of associated lesions the prognosis was better than expected. Seventy-six patients were alive at the end of the study, no one being critically ill. No death occurred among the patients with intact ventricular septum. Patients with pulmonary stenosis as a group developed symptoms later, were less handicapped and had a better prognosis than those without a pulmonary stenosis. One third of the patients had dysrhythmias. Eight patients having a 3rd degree AV-block. Auscultatory findings were not of too great a help when diagnosing C-TGA. Forty-seven patients had a single second sound, of these 37 had pulmonary stenosis. In 60 % of the patients, where information was available, the second sound was reported to be of normal intensity. Our surgical experience is documented and discussed. Palliative procedures were done with successful results and low mortality. Totally corrective procedures were performed in 9 patients with 4 deaths.     

Heart transplantation in infants with idiopathic hypertrophic cardiomyopathy

Abstract:  Whereas it is well known that idiopathic HCM can present in newborns and infants, little information is available on HT in this very young age group. We report a series of 17 infants with idiopathic HCM, including two neonates with rapidly progressive severe HF for whom HT was necessary. When HF manifests in a newborn/infant with idiopathic HCM and extreme cavity size reduction, the possibility of a rapidly progressive clinical course should be anticipated and HT may become the only available therapeutic solution.