转录因子ZFP580在缺氧预处理抗大鼠心肌细胞缺氧/复氧损伤中的作用

 目的：通过观察缺氧预处理对心肌细胞缺氧/复氧损伤的保护作用及锌指核转录因子ZFP580表达的改变,探讨ZFP580的作用及机制。方法：培养大鼠H9c2心肌细胞,分为3组：（1） 缺氧/复氧(H/R)组：H9c2心肌细胞换用模拟缺血溶液(pH=6.2)缺氧(95% N2 + 5% CO2)培养3 h,复氧培养2 h;（2） 缺氧预适应(HPC)组：H9c2心肌细胞经3个循环的短暂缺氧(10 min)/复氧(20 min)处理后,进行同上H/R实验;(3) 对照(C)组：正常培养的H9c2心肌细胞。通过MTT染色及LDH水平判定HPC的作用。Western blotting方法观察心肌细胞中转录因子ZFP580表达及ERK1/2磷酸化情况,以及ERK1/2磷酸化抑制剂PD98059对ZFP580表达的影响。分别构建高/低表达ZFP580的慢病毒载体并转染H9c2心肌细胞,经H/R实验后利用Annexin V-PE/7-AAD染色及流式细胞术检测H9c2细胞凋亡情况,Western bloting方法观察caspase-3活化情况。结果：HPC能显著改善H/R处理后H9c2心肌细胞存活率降低和LDH漏出的现象。Western blotting结果显示,HPC组心肌细胞中ZFP580表达及ERK1/2磷酸化程度较H/R处理组明显上升,且PD98059预处理明显抑制HPC诱导的ZFP580的表达上调。慢病毒介导的基因转染实验发现,ZFP580高表达的H9c2心肌细胞在H/R损伤后凋亡率降低且细胞中活化caspase-3表达下降。结论：HPC可引起心肌细胞中转录因子ZFP580表达上调,ZFP580作为ERK1/2通路的下游靶分子发挥抗心肌细胞凋亡的作用。ZFP580表达上调可能作为内源性保护机制之一介导了HPC的细胞保护作用。     

核转录因子FOXP3在肺癌组织中的表达及意义

目的： 检测核转录因子FOXP3在不同病变肺组织中的表达，分析CD4+ CD25+ 调节性T细胞在不同病变肺组织中的浸润情况，并进一步探讨不同病理类型的肺癌组织中FOXP3表达的异同。方法: 使用RT-PCR及Western blotting方法，检测21例肺癌、7例支气管扩张、5例炎性假瘤、3例结核球以及15例病灶旁手术切除正常肺组织共153份标本中FOXP3 mRNA及蛋白的表达。结果: 肺癌、肺良性病变及病灶旁正常肺组织FOXP3 mRNA及蛋白的表达阳性分别为41/63、8/45、0/45（P<0.05），肺癌与肺良性病变组织均有FOXP3 mRNA及蛋白表达，分析其平均吸光度A值之间有显著差异（P<0.01）。病灶旁正常肺组织FOXP3 mRNA及蛋白无表达。不同病理类型肺癌组织中均有FOXP3 mRNA及蛋白的表达，分析其平均吸光度A值之间无显著差异（P>0.05）。结论: FOXP3可作为CD4+ CD25+调节性T细胞的一种标志物。肺癌与肺良性病变组织均有FOXP3 mRNA及蛋白表达，FOXP3在肺癌组织中表达强于肺良性病变组织。     

转录因子Foxp3在子宫内膜异位症局部组织中的表达及意义

目的： 检测Foxp3在子宫内膜异位症组织中的表达,探讨内异症的发病机制。方法: 通过免疫组化染色,观察21 例子宫内膜异位症卵巢巧克力囊肿及同一患者盆腔腹膜中Foxp3的表达,并与10 例正常子宫内膜和10例正常腹膜进行比较。结果: 子宫内膜异位症患者卵巢巧克力囊肿及其盆腔腹膜中均可见到Foxp3阳性细胞表达,且二者Foxp3阳性细胞计数比较差异无显著;正常子宫内膜和正常腹膜中无Foxp3阳性细胞表达。结论: Foxp3启动了调节性T细胞的免疫抑制功能,使盆腔内免疫环境呈免疫耐受状态,当有活性的子宫内膜细胞进入盆腔后没有被免疫系统识别和清除,而是在盆腔内异位处发生侵袭、种植及进一步生长, 这可能是子宫内膜异位症发生的机制之一。     

Genetic and Functional Analyses of ZIC3 Variants in Congenital Heart Disease

Mutations in zinc‐finger in cerebellum 3 (ZIC3) result in heterotaxy or isolated congenital heart disease (CHD). The majority of reported mutations cluster in zinc‐finger domains. We previously demonstrated that many of these lead to aberrant ZIC3 subcellular trafficking. A relative paucity of N‐ and C‐terminal mutations has, however, prevented similar analyses in these regions. Notably, an N‐terminal polyalanine expansion was recently identified in a patient with VACTERL, suggesting a potentially distinct function for this domain. Here we report ZIC3 sequencing results from 440 unrelated patients with heterotaxy and CHD, the largest cohort yet examined. Variants were identified in 5.2% of sporadic male cases. This rate exceeds previous estimates of 1% and has important clinical implications for genetic testing and risk‐based counseling. Eight of 11 were novel, including 5 N‐terminal variants. Subsequent functional analyses included four additional reported but untested variants. Aberrant cytoplasmic localization and decreased luciferase transactivation were observed for all zinc‐finger variants, but not for downstream or in‐frame upstream variants, including both analyzed polyalanine expansions. Collectively, these results expand the ZIC3 mutational spectrum, support a higher than expected prevalence in sporadic cases, and suggest alternative functions for terminal mutations, highlighting a need for further study of these domains.     

Detailed mapping of a congenital heart disease gene in chromosome 3p25

Distal deletion of chromosome 3p25-pter (3p− syndrome) produces a distinct clinical syndrome characterised by low birth weight, mental retardation, telecanthus, ptosis, and micrognathia. Congenital heart disease (CHD), typically atrioventricular septal defect (AVSD), occurs in about a third of patients. In total, approximately 25 cases of 3p− syndrome have been reported world wide. We previously analysed five cases and showed that (1) the 3p25-pter deletions were variable and (2) the presence of CHD correlated with the proximal extent of the deletion, mapping a CHD gene centromeric to D3S18. To define the molecular pathology of the 3p− syndrome further, we have now proceeded to analyse the deletion region in a total of 10 patients (five with CHD), using a combination of FISH analysis and polymorphic markers, for up to 21 loci from 3p25-p26. These additional investigations further supported the location of an AVSD locus within 3p25 and refined its localisation. Thus, the critical region was reduced to an interval between D3S1263 and D3S3594. Candidate 3p25 CHD genes, such as PMCA2 (ATP2B2), fibulin 2, TIMP4, and Sec13R, were shown to map outside the target interval. Additionally, the critical region for the phenotypic features of the 3p− phenotype was mapped to D3S1317 to D3S17 (19-21 cM). These findings will accelerate the identification of the 3p25 CHD susceptibility locus and facilitate investigations of the role of this locus in non-syndromic AVSDs, which are a common form of familial and isolated CHD.


Keywords: congenital heart disease; chromosome 3p25     

冠心病患者血清C型钠尿肽的变化及其临床意义

目的:探讨冠心病(CHD)患者血清C型钠尿肽(CNP)的变化及临床意义。方法:采用放射免疫分析测定了116例CHD患者和40例正常对照组血清CNP水平,进行对照统计分析。结果:CHD组血清CNP水平显著地高于正常对照组(t=6.368,P<0.01),Ⅰ、Ⅱ、Ⅲ及Ⅳ级心功能组血清CNP水平显著高于好转出院组(t=8.452,P<0.01)。结论:CHD组血清CNP显著升高,并随心功能分级递增,死亡者增加更明显。     

Hyperphalangy and clinodactyly of the index finger with Pierre Robin anomaly: Catel-Manzke syndrome. A case report and review of the literature

Mandibular hypoplasia, glossoptosis, U-shaped cleft palate (Pierre Robin anomaly), associated with bilateral index finger malformation and congenital heart disease are described in a male, newborn infant. Review of the features of seven previously published patients, in addition to the patient reported here, confirms the existence of a distinct dysmorphogenesis syndrome. Although all of these eight patients have been males, and most were sporadic, the etiology of this rare malformation syndrome is unknown.     

Partial deletion of the short arm of chromosome 3: further delineation of the 3p25 - 3pter syndrome

A male newborn with partial deletion of the short arm of chromosome 3 is described. The patient shares most of the features with the previously reported cases. In addition, cardiac, skeletal and gastrointestinal anomalies not previously reported are described. These characteristics may help in further delineation of the syndrome.     

流式细胞术在母婴血型不合新生儿溶血病检测中的应用

目的建立流式细胞仪检测母婴血型不合新生儿溶血病（HDN）的方法。方法对临床送检的115例拟诊新生儿溶血病标本以流式细胞仪进行直接抗人-IgG试验、血清游离抗体检测及红细胞放散液抗体检测3项试验，选择FITC标记的单克隆二抗作为与红细胞特异性抗体结合的抗体。同时以试管抗球蛋白法进行3项试验作为对照，比较两方法的差异。结果建立了以流式细胞仪检测新生儿溶血病的实验方法：细胞采集比例为54．5％；阴性阈值2％；流式法对ABOHDN和RhHDN的检测阳性率分别为86％和100％。试管法检测阳性率分别为50％和100％。结论流式法具有敏感性高，特异性强，结果易判定，客观、标准等优点，为新生儿溶血病检测提供了一种可靠的诊断依据。     

17-OH、17-KS、VMA、ALD和COR在心血管疾病中的诊断价值

目的：探讨尿17羟皮质类固醇（17-OH）、17酮皮质类固醇（17-KS）、香草扁桃酸（VMA）、血浆醛固酮（ALD）和血清皮质醇（COR）在心血管疾病中的水平变化及应用价值。方法：应用微柱比色法和电化学发光法对116例原发性高血压（PH）患者、52例继发性高血压（SH）患者和21例冠心病（CHD）患者进行24h尿液17．OH、17-KS、VMA和血浆ALD、血清COR的检测,以30例健康人作为正常对照组。结果：与正常对照组比较,SH组17．OH、17-KS、VMA、ALD和COR水平均较对照组和PH组增高,具统计学意义（P〈0．01,P〈0．001）;CHD组尿17-OH、17．OH和血浆ALD、血清COR水平较正常对照组明显增高,具统计学意义（P〈0．01,P〈0．05）;相关实验显示,ALD与17-OH、17-KS之间呈正相关（r=0．502、0．796,P〈0．01）;COR与17-OH、17-KS之间亦呈正相关（r=0．648、0．584,P〈0．01）;ALD、COR与VMA之间无相关性（P〉0．05）。结论：尿17．OH、17-KS、VMA、血浆ALD、血清COR水平联检在PH和SH的鉴别诊断、针对性治疗和CHD的预后判断等方面具有重要临床价值。     

完全性大动脉转位275例的外科治疗

目的 评价伴随不同种类解剖畸形的完全性大动脉转位通过不同术式取得的治疗效果.方法 通过大动脉调转术、双向腔肺吻合术、Rastelli矫治术、Fontan术、Senning术等治疗伴随室间隔缺损、肺动脉狭窄、房间隔缺损、动脉导管未闭、下腔静脉中断、永存左上腔静脉、冠状动脉畸形、主动脉弓缩窄等畸形的完全性大动脉转位,并评价术后生存率.结果 全组275例,早期死亡14例（5.09％）：大动脉调转术后死亡10例（10/243,4.12％）,其余术式术后死亡4例（4/32,12.50％）;生存261例,其中双向Glenn术、改良Fontan和全腔肺动脉吻合术后患儿发绀明显缓解,大动脉调转术和改良Senning术后患儿发绀消失,生长发育正常.结论 完全性大动脉转位可通过多种术式治疗,新生儿通过大动脉调转术治疗取得较好效果.