22q11微缺失所致先心病的产前诊断

目的 探讨在先心病胎儿中进行22q11微缺失产前诊断的必要性及可行性.方法 对产前胎儿超声检查诊断为先天性心脏畸形的孕妇16例行羊膜腔穿刺或脐静脉穿刺获取胎儿细胞,并行染色体核型分析及双色荧光原位杂交检测22q11微缺失.结果 16例中检出22q11微缺失1例.结论 在先心病胎儿中行22q11微缺失产前诊断是有必要的,...     

新一代测序技术对 22q11.2微缺失所致的胎儿心脏发育畸形的产前筛查价值

目的分析新一代测序技术对 22q11.2微缺失所致的胎儿心脏发育畸形的产前筛查价值。方法选取 2018年 7月至 2020年 3月吉林省妇幼保健院收治的 78例可疑胎儿心脏发育畸形者的孕妇作为受试对象，均接受跟踪随访明确胎儿心脏发育情况，采用新一代测序技术、多重连接探针扩增(MLPA)技术检测 22q11.2微缺失情况，并利用 MLPA技术对父母溯源。统计随访和检测结果，采用微阵列比较基因组杂交( arrayCGH)技术进行全基因组扫描分析，验证上述检测结果。将 arrayCGH验证结果作为“金标准”分析新一代测序技术对 22q11.2微缺失所致的胎儿心脏发育畸形的产前筛查价值。结果 78例受试对象中有 35例胎儿心脏发，育畸形者，经新一代测序技术、 MLPA、arrayCGH检测分别有 12例、 14例、 14例 22q11.2微缺失； 43例胎儿心脏发育正常者经新一代测序技术、 MLPA、arrayCGH检测分别有 1例、 1例、 1例 22q11.2微缺失；有 2例经 MLPA检测发现 22q11.2微缺失属于父源，余 13例均为新发 22q11.2微缺失；以 arrayCGH验证结果为“金标准”，新一代测序技术诊断 22q11.2微缺失的灵敏度、特异度、准确度分别为 86.70%、100.00%、97.40%，Kappa一致性检验值为 0.913，MLPA诊断 22q11.2微缺失的灵敏度、特异度、准确度分别为 100.00%、100.00%、10.00%，Kappa一致性检验值为 1.000，且新一代测序技术、 MLPA检测结果与“金标准”有显著关联性( χ2=59.43、71.70，P<0.05)，差异无统计学意义( χ2=0.50、0.00，P>0.05)。结论 22q11.2微缺失是胎儿     

“黔药”临床应用心得

“黔药”系指“产于贵州,在中医药理论指导下使用的药物及以苗族药物为代表,包括侗族、布依族、水族等少数民族在其聚居地防病治病的民族药物”.笔者在长期研究“黔药”中,深感其疗效显著,故将临床应用心得体会简述如下.     

转录因子Nkx2.5、GATA4在先天性心脏病产前诊断中的研究

目的研究转录因子Nkx2.5、GATA4在先天性心脏病(CHD)产前诊断中的临床价值。方法 50例超声心动图确诊胎儿为先天性心脏病的孕妇,抽取孕妇羊水、脐血或引产胎儿脐血,采用多重连接探针扩增技术(MLPA)检测,分析其染色体核型、 MLPA检测结果。结果 50例先天性心脏病胎儿中6例染色体核型分析异常,其中3例为21-三体综合征, 2例为18-部分三体综合征, 1例为46, XX,der(6)(q16q22);剩余44例先天性心脏病胎儿染色体核型分析结果正常。50例先天性心脏病胎儿进行Nkx2.5、GATA4基因的突变筛查,结果未发现任何突变。1例先天性心脏病患儿通过染色体微阵列分析(CMA)在染色体8p23.2位置检出一段约859 kb的拷贝数变异(CNV),涉及OMIM基因CSMD1等,可能为多态改变。结论先天性心脏病胎儿不存在Nkx2.5、GATA4基因异常,这可能一方面是由于所选样本量过小,有待于扩大样本量,以便进行更广泛的筛查;另一方面也可能因为我国和国外的人种差异,因此需进一步扩大先天性心脏病的样本数量进行更深入的研究,以进一步揭示先天性心脏病的发病机制。     

全麻下治疗先天性心脏病的临床观察

目的全麻下治疗先天性心脏病临床观察。方法从本院资料库中随机抽取先天性心脏病患儿44例,患者的各项检测项目都非常正常,并由有关科室诊断后决定,所有患者均能正常承受全麻下的先天性心脏病手术治疗,观察术前、术中、术后疗效,并记录其临床状况。结果 44例先天性心脏病患者中,开放主动脉后有36例自动复跳,8例微颤一次后复跳,辅助循环1h内至血流动力学保持平稳。没有出现术后并发症,手术后心功能正常,经过复查ECG、TTE均属正常,切口正常愈合,可准备出院。结论全麻下进行治疗先天性心脏病手术,其效果安全可靠、成功率高、并发症少,具有很大的推广意义。     

贵州省苗族、布依族及汉族 EB病毒感染情况及鼻咽癌诊断试验效果评价研究

目的调查贵州省苗族、布依族及汉族EB病毒感染情况并探讨EB病毒特异性Zta-IgA、EBNA1-IgA与VCA-IgA抗体定量检测对鼻咽癌的诊断价值。方法采用随机抽样的方法抽取苗族、布依族及汉族共3040例研究对象,收集研究对象的基本信息;采用ELISA法检测研究对象血浆EB病毒的Zta-IgA、EBNA1-IgA、VCA-IgA标志物水平,分析上述指标诊断鼻咽癌的价值。结果3040例研究对象中,Zta-IgA阳性率为15．03％;EBNA1-IgA阳性率为16．09％;VCA-IgA阳性率为14．41％（χ2=16．027,P=0．000）;Zta=IgA、EBNAI-IgA、VCA-IgA阳性率均为布依族最高（Pd0．05）;〉45岁组Zta-IgA、EBNA1-IgA、VCA-IgA阳性率均明显高于≤45岁年龄组（P〈0．05）;吸烟、饮酒可以明显提高Zta-IgA、EBNA1-IgA、VCA-IgA阳性率（P〈0．05）;三者联合检测对诊断鼻咽癌的灵敏度和特异度均明显升高。结论贵州省少数民族EB感染率水平较高,应开展Zta-IgA、EB-NA1-IgA、VCA-IgA监测;三者联合检测对鼻咽癌的早监测、早发现有积极意义。     

男性不育症患者Y染色体微缺失分析

目的 分析1892例男性不育症患者的Y染色体微缺失及染色体核型。方法 根据精液化参数,1892例男性不育症患者分为无精子症组(257例)、少精子症组(293例)和精液正常组(1342例)。采用多重PCR法扩增患者序列标签位点,检测位点的缺失情况,并对其外周血进行染色体核型分析,探讨性染色体异常与男性生育及无精子因子关系。结果 1892例男性不育症患者中检测出Y染色体微缺失44例(2.33%)。与精液正常组相比,无精子症组、少精子症组Y染色体微缺失率较高(10.89%、3.75%vs.0.37%)(P<0.01),且无精子症组更高(P<0.01)。1892例男性不育症患者检测出性染色体异常17例(0.90%),包括无精子症组15例、精液正常组2例。17例性染色体异常患者同时检出Y染色体微缺失共计8例,均为无精子症组患者。结论 无精子因子基因缺失影响精子发生,可能联合Y染色体核型异常进一步降低精子发生。     

彩超血流检测胎儿心脏瓣膜反流的效果分析

目的探讨彩超血流检测胎儿心脏瓣膜反流的效果,希望为胎儿先天性心脏病的早期筛查提供参考。方法 2015年7月至2016年8月选择在我院行产前超声检查的妊娠孕妇共320例,都为单胎妊娠孕妇,所有孕妇都给予彩色多普勒超声检查,记录胎儿心脏瓣膜反流情况,同时对胎儿进行随访调查,记录新生儿的先天性心脏病发生情况。结果在320例孕妇中,检测到尖瓣少量反流胎儿、二尖瓣少量反流胎儿、二尖瓣和三尖瓣同时少量反流胎儿分别为16、2、8例,总检出26例,检出率为8.13%,其中轻度反流24例,中度反流2例,无重度反流。所有新生儿都顺利分娩,彩超血流检测异常的胎儿显示患先天性心脏病新生儿4例,非先天性心脏病新生儿22例,彩超血流检测胎儿心脏瓣膜反流无漏诊情况,检出敏感性为100.0%。结论将彩超血流检测技术应用于胎儿心脏瓣膜反流检测中能有效检出瓣膜反流现象,对于产前检查精度的提高、胎儿的健康发育有重要作用。     

某院2010-2011年幽门螺杆菌现症感染调查分析

目的了解某院2010--2011年幽门螺杆菌（Hp）现症感染率。方法对3841例患者的Hp检测结果进行回顾性总结。结果3841例患者Hp感染阳性1467例，阳性率为44％；患者年龄小于或等于20岁，Hp感染阳性204例；患者年龄大于20岁，Hp感染Fn性1389例；其中检查苗族患者2616例，侗族患者696例，苗族患者中Hp感染阳性1181例，侗族患者Hp感染Fn性275例，其他族别患者27例，Hp感染Fn性11例。结论Hp的感染随经济条件，医疗条件，生活方式不同，人种不同，国家不同，地区不同感染率也不相同。调查随年龄增大感染率也明显增高。     

MLPA在诊断1例复杂性先天性心脏病中的应用

目的采用多重连接探针扩增技术(MLPA)对脐带血标本进行进行检测,分析在复杂性先天性心脏病诊断中应用的诊断价值。方法①对1例复杂性先天性心脏异常胎儿取脐带血3 mL脐带血细胞进行培养和标本制作,利用G显带技术对染色体核进行分析;②并取200μL提取DNA后采用MLPA技术进行检测。结果 G显带染色体核型分析46,XY,MLPA检测结果为与先天性心脏病相关的2个探针对应的片段大小位置在3100的电泳图上荧光峰值相比正常对照明显出现减半,统计缺失区域的荧光比值为0.450和0.339(正常值:0.7¹.3)。结论患儿在与先天性心脏病相关的基因位点(GATA4)的上游存在杂合性缺失,缺失的片段大小约为1.5kb。     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Polymorphisms in genes involved in neurotransmission in relation to smoking

Smoking behavior is influenced by both genetic and environmental factors. The genetic contribution to smoking behavior is at least as great as its contribution to alcoholism. Much progress has been achieved in genomic research related to cigarette-smoking within recent years. Linkage studies indicate that there are several loci linked to smoking, and candidate genes that are related to neurotransmission have been examined. Possible associated genes include cytochrome P450 subfamily polypeptide 6 (CYP2A6), dopamine D₁, D₂, and D₄ receptors, dopamine transporter, and serotonin transporter genes. There are other important candidate genes but studies evaluating the link with smoking have not been reported. These include genes encoding the dopamine D₃ and D₅ receptors, serotonin receptors, tyrosine hydroxylase, trytophan 2,3-dioxygenase, opioid receptors, and cannabinoid receptors. Since smoking-related factors are extremely complex, studies of diverse populations and of many aspects of smoking behavior including initiation, maintenance, cessation, relapse, and influence of environmental factors are needed to identify smoking-associated genes. We now review genetic polymorphisms reported to be involved in neurotransmission in relation to smoking.     

Tramadol concentrations in blood and in cerebrospinal fluid in a neonate

Based on blood and cerebrospinal fluid samples collected in a full-term neonate, the penetration of tramadol in the central nervous system is described. Following intravenous administration of tramadol, a lag time of about 4 h was observed until full blood–brain equilibration was achieved. This pharmacokinetic observation is in line with a recent pharmacodynamic evaluation of the central opioid effects of tramadol in adults.     

Genotoxic effects of chlorophenoxy herbicide diclofop-methyl in mice in vivo and in human lymphocytes in vitro

Diclofop-methyl (DM) is a chlorophenoxy derivative used in large quantities for the control of annual grasses in grain and vegetable crops. In this study, the genotoxic effects of DM were investigated by measuring chromosomal aberrations (CAs) in mouse bone-marrow cells and CA and the comet assay in human peripheral lymphocytes. Mice were treated with 15.63, 31.25, 62.5, and 125?mg/kg body weight of DM intraperitoneally for 24 hours, and 15.63-, 31.25-, 62.5-, 125-, and 250-µg/mL concentrations were applied to human lymphocytes for both 24 and 48 hours. In in vivo treatments, DM significantly, but not dose dependently, increased the total chromosome aberrations, compared to both negative and solvent controls. Cell proliferation was significantly, but not dose dependently, affected by all doses. In in vitro treatments, DM (except 15.63 µg/mL) significantly and dose dependently increased the frequency of chromosome aberrations. Also, 250 µg/mL of 48-hour treatment was found to be toxic. Cell proliferation was significantly and dose dependently affected by DM applications, when compared to negative control. In in vitro treatments, DM significantly decreased the mitotic index only at the highest concentration for 24 hours, and 62.5- and 125-µg/mL concentrations for 48 hours. In the comet assay, a significant and dose-dependent increase in comet-tail intensity was observed at 62.5-, 125-, and 250-µg/mL concentrations. The mean comet-tail length was significantly increased in all concentrations. Our results demonstrate that DM is genotoxic in mammalian cells in vivo and in vitro.     

2010调脂治疗领域进展

2010年在调脂治疗领域针对他汀治疗心血管病的防治又进行了许多探索。本文通过综述他汀类药物的国际大规模临床试验结果,重新评价了他汀类药物在冠心病一级预防和冠心病二级预防中的地位,阐明了强化他汀治疗的意义;对他汀的心肾保护作用和安全性新证据进行了说明。