46例高苯丙氨酸血症新生儿早期干预效果分析

目的对高苯丙氨酸血症（hyperphenylalaninemia，HPA）患儿早期干预效果进行分析，探讨干预后的经济效益、社会效益和有效干预的方法。方法通过新生疾病筛查和免费鉴别诊断，以早期诊断，并立即给予免费6年的干预。结果几年来。共确诊HPA患儿46例，由于有效解决了患儿家庭的经济负担，提高了患儿家长配合治疗的积极性，使患儿持续治疗率达到100％，治疗良好率97．8％。结论广泛宣教、政策干预、新生儿疾病筛查、诊断治疗、家庭饮食指导、实行保偿制等综合干预措施，可有效提高筛查率、患儿检出率，实现早发现、早诊断、持续有效的治疗，达到提高出生人口素质的目的。     

多重扩增子高通量测序对高苯丙氨酸血症基因变异实验室检测效率的研究

目的 对高苯丙氨酸血症(hyperphenylalaninemia,HPA)干血片DNA样本进行多重扩增子高通量测序检测,研究该方法对HPA潜在病因的实验室诊断价值.方法 选取既往70例生化筛查为HPA的患儿干血片,提取DNA后使用覆盖126种遗传病130个基因的扩增子建库试剂盒建库,进行高通量测序和数据分析,获得样本基因变异信息.经一代测序验证位点准确性后,分析对样本具有诊断价值的变异位点信息进行疑似病因判定,评价高通量测序的检测和诊断效能.结果 高通量测序结果和既往部分样品的一代测序结果完全吻合.70例样本中,5例为PAH和PTPS纯合突变,53例检测出PAH或PTPS单个基因2～3个杂合突变位点,还有2例检出HPA信号通路相关的SPR基因或GCH 1基因各1个突变.检测结果中c.158G>A、c.728G>A、c.1068C>A、c.1238G>C、c.611A>G位点为PAH基因频率最高的5个突变.结论 通过高通量测序技术,可准确检测基因突变,提供病因解释,为后续召回和临床诊断提供重要参考.     

高苯丙氨酸血症的抽搐机制研究

目的四氢生物喋呤缺乏症和苯丙酮尿症均可导致继发性癫痫,本研究拟探讨两类患者的临床与实验室特点。方法将两组患者出现癫痫的年龄、发作形式、脑电图特点及治疗预后进行比较。结果在391例晚治的高苯丙氨酸血症患者中,共有98例苯丙酮尿症和12例四氢生物喋呤缺乏症患者合并癫痫。98名苯丙酮尿症患者出现癫痫发作的年龄是10.7±4.6(4.5~27.1)个月,表现为多种形式,其中55例(56.1%)表现为婴儿痉挛症。经丙戊酸钠和其他抗癫痫药物治疗后,癫痫较难控制,经低苯丙氨酸饮食治疗后临床发作及脑电图均有所减轻。12例四氢生物喋呤缺乏症患儿出现癫痫的年龄为5.1±1.9(2.7~11.0)个月,主要表现为肢体铅管样扭转,哈气样症状。其中10例患者进行了脑电图检查,3例有轻度的痫样放电,7例脑电图正常。治疗后随访脑电图无特异性变化。在服用美多巴后,发作立即得到控制。结论四氢生物喋呤缺乏症和苯丙酮尿症导致癫痫的机制不同,两组患者发作开始年龄、形式、脑电图表现差异显著,治疗方法及预后完全不同。     

荧光定量PCR检测HBV-DNA与化学发光酶免疫法检测乙肝五项的相关性调查

目的 探讨FQ-PCR检测HBV-DNA与CLEIA检测乙肝五项之间的相关性.方法 将以FQ-PCR法检测筛选的HBV-DNA阳性结果的血清用CLEIA法对其进行乙肝病毒血清学标志物（即乙肝五项）的检测.结果 大三阳与小三阳所占全部样本的比例最高,其低中高HBV-DNA水平的比例分别为17.2％,17.2％,65.5％和81.8％,15.2％,3.0％,而且差异有统计学意义（P＜0.05）;HBeAg与HBeAb阳性标本的HBV-DNA水平不同,差异有统计学意义（P＜0.05）.结论 FQ-PCR检测HBV-DNA水平与CLEIA检测的乙肝五项水平在判断患者乙肝病毒感染病程方面的相关性较好,但乙肝五项定量结果数值与HBV-DNA载量数值并没有直接相关的关系.     

1235 AutoDELFIA在新生儿甲状腺功能低下症筛查中的应用

目的通过分析1235 AutoDELFIA在新生儿甲状腺功能低下症的筛查情况,评价其使用情况。方法用1235 AutoDELFIA对162600例新生儿血样进行甲状腺功能低下症筛查,分析实验结果及质控数据。结果筛查出可疑阳性3300例,电话召回3065例,召回率92.88%;召回后确诊甲状腺功能低下症10l例,高TSH血症165例,确诊率8.68％,甲低发病率1／1610。质控在控率95.23％,总体变异系数9.65％。结论1235 AutoDELFIA稳定性、均一性良好,可用于新生儿疾病筛查。     

抗核抗体荧光滴度判读参考标准的建立

目的 建立一套简单实用的人工判读抗核抗体荧光滴度结果的参考标准.方法 选择卫生部室间质评质控品:均质型1∶1000,颗粒型1∶320.通过3.2倍稀释获得:均质型1∶320、均质型1∶100、颗粒型1∶100样本.随机用四个批次的试剂分别对样本进行测定,运用EUROIMMUN全自动判读仪读取并记录每个样本滴度的灰度值和图像.按照实验室室内质控的建立方法,计算灰度值的均值,该灰度值对应图像作为参考标准图像,并对该图像进行临床验证.结果 计算所得各核型不同滴度的灰度值均值,得到相应图像作为参考标准图像.临床验证,参考标准图像前后人工判读的准确性有所提高(P＜0.05),一致性有所提高(P＜0.05).结论 通过参考标准的建立能够提高人工判读结果的准确性和一致性,有利于标准化的建立.     

宝鸡地区2007∽2013年新生儿筛查高苯丙氨酸血症结果分析

目的对宝鸡市2007年∽2013年间的204 868例新生儿筛查苯丙氨酸浓度测定,并对部分阳性患儿血、尿标本进行MS/MS、GS/MS分析,探讨我市PKU发病情况和发病率。方法采用ELISA时间分辨荧光免疫多标记免疫分析法（DELFIA）检测血苯丙氨酸浓度。结果筛查出高苯丙氨酸血症71例,其中经典型PKU17例,轻度PKU22例,轻度HPA30例,BH4缺乏症2例,高HPA检出率为1/2885（71/204868）,高出全国HPA发生率（1/11444）,BH4缺乏症为2.82%。结论开展新生儿筛查是早期发现HPA的有效方法,对HPA患儿应进一步进行鉴别诊断,排除四氢喋呤缺乏症,并进行及时治疗,避免残障儿的发生。     

罗氏Cobas e601全自动免疫分析仪检测人附睾蛋白4（HE4）的性能验证

目的：验证和评价罗氏Cobas e601全自动免疫分析仪检测系统人附睾蛋白4项目的分析性能。方法参考美国临床实验室标准化协会(CLSI)系列文件和相关文献,对罗氏Cobas e601电化学发光免疫检测系统测定血清人附睾蛋白4(HE4)的精密度、准确度、分析灵敏度、分析测量范围、生物参考区间5大分析性能进行验证和评价,并将实验结果与厂商声明的性能或公认的质量标准进行比较。结果测定均值为100.66pmol/L的质控样本,验证后S批内为0.827,S总为1.679;测定均值为1296.60pmol/L的质控样本,验证后S批内为6.077,S总为5.596。S批内≤1/4TEa,S总≤1/3TEa(CLIA'88)。准确度在±1%以内,低于卫生部允许的偏差范围;分析灵敏度<5 pmol/L;线性范围为60.65pmol/L~1364.50 pmol/L;生物参考区间在0.00pmol/L~104.00 pmol/L,均与厂商提供的参数接近。结论罗氏Cobas e601电化学发光检测HE4的主要分析性能均与厂商声明一致。本系统检测性能符合CAP要求。     

新生儿高胆红素血症脑干听觉诱发电位检测的意义

目的:观察高胆红素血症对新生儿脑干听觉功能的影响。方法:对208例高胆红素血症新生儿进行脑干听觉诱发电位(BAEP)检测。结果:新生儿高胆红素血症的BAEP异常率为57.21%。以Ⅲ、Ⅴ波异常较多。结论:无症状性高胆红素血症存在脑干听觉功能损害,积极的BAEP检测有重要意义。     

床边血糖仪与全自动生化分析仪检测结果的对比分析

目的 评估床边(POCT)血糖仪与全自动生化分析仪检测血糖结果的相关性,保证POCT血糖仪检测结果的准确性.方法 用高、中、低血糖浓度均含盖其中的7份标本分别用28台POCT血糖仪和全自动生化分析仪检测其血糖值.以全自动生化分析仪检测值为标准,用POCT血糖仪检测值与标准值进行对比分析.结果 经过对比发现全院28台POCT血糖仪有24台测定值偏倚在允许范围内,4台测定结果不准确.结论 POCT血糖仪的检测结果应定期与全自动生化分析仪的检测结果进行对比分析,以保证其检验结果的准确性.     

产前筛查和基因多态性位点在唐氏综合征产前诊断中的应用

目的 在建立可靠的产前筛查方法的同时，采用快速，简便，准确的产前诊断方法，防止唐氏综合征（DS）患儿的出生，方法 采用酶联免疫方法测定妊娠14-20w孕妇血清甲胎蛋白（AFP）和绒毛膜促性腺激素β亚基（β-HCG）浓度，结合孕妇年龄，孕周和体重，用计算机软件进行分析，得到每位孕妇所怀胎儿DS风险系数，对筛查出胎儿唐氏综合征高风险孕妇，再利用21号染色体上的6个多态性位点对其作产前基因诊断。结果 经产前筛查，在395例孕妇中发现10例胎儿唐氏综合征高风险孕妇，其中1例产前基因诊断为胎儿唐氏综合征，与染色体核型分析结果相符。结论 产前筛查结合基因多态性在唐氏综合征产前诊断中具有很好的应用价值。     

Phenylalanine hydroxylase from the sponge Geodia cydonium: implication for allorecognition and evolution of aromatic amino acid HYDROXYLASES

The prophenoloxidase activating system is a defense system, frequently reported both in protostomes and in deuterostomes. The final product of the phenoloxidase activity is melanin which is ubiquitously present throughout the metazoan kingdom. The melanin synthesis pathway starts with the amino acid [aa] phenylalanine which is converted to tyrosine by the phenylalanine hydroxylase [PAH]. We show that after allo-transplantation in the marine sponge Geodiacydonium PAH is upregulated in the grafts. Enzyme determination studies revealed that PAH activity increases by three-fold two d after transplantation and reaches its maximum after 3 d (by 3.7-fold). This finding was supported by determining the steady-state level of the mRNA for PAH. Furthermore the cDNA, encoding this enzyme was isolated from G. cydonium. Its deduced aa sequence encodes a protein of 51 kDa. Alignment studies indicate that the sponge PAH shares the consensus pattern as well as one characteristic pterin-binding site with the biopterin-dependent aromatic amino acid hydroxylases. Phylogenetic analysis of sponge PAH shows that all metazoan PAH fall in one group with the sponge PAH as the oldest member. The related classes of enzymes, the tyrosine hydroxylases and the tryptophan hydroxylases are statistically significantly separated from PAH; the tyrosine hydroxylase diverged as the first class from the common ancestor, a process which was calculated to have occurred ≈500 million years ago. It is concluded that in the sponge model system G. cydonium allogeneic rejection involves an upregulation of PAH, an enzyme initiating the pathway to melanin synthesis.     

第二代血清维生素B12实验室参考区间的建立

目的 建立第二代血清维生素B12检测试剂的实验室参考区间,为临床监测血清维生素B12水平提供依据.方法 验证分析了第二代血清维生素B12的精密度、线性范围和最大稀释倍数,并用电化学发光法检测了120例健康人第二代血清维生素B12水平.结果 (1)重复变异系数高值为1.55％、低值为1.63％,期间变异系数高值为1.60％、低值为1.56％.(2)线性分析,回归方程为Y=X-0.0016,r=0.9999.(3)维生素B12的最大稀释倍数为5倍.(4)参考区间为235.2～1000.0pg/mL,不同性别比较,差异无统计学意义(P＞0.05),不同年龄段比较,差异无统计学显著意义(P＞0.05).结论 建立了本实验室维生素B12参考区间,为维生素B12检测的临床应用和监测提供理论依据.     

解决空域控制问题时的遗传算法

空域控制问题就是调整可能进入一定空域的多架飞机的航向，使之在该空域内能安全恰当地飞行。作者首先给出了此问题的数学表示，并讨论了解决空域控制问题的途径及其困难，其次在给出了遗传算法的框架表示的基础上，提出了解决空域控制问题的遗传算法设计，最后给出了在一个具体空域控制问题上的遗传算法的解答并对此解答作了些讨论。     

Non-invasive Screening for Treatment of Heifers with the Anabolic Steroid Melengestrol Acetate (MGA) by Feces Analysis

Abstract

For eight weeks, two heifers each had been orally administered daily doses of 0, 1.5, or 5 mg melengestrol acetate (MGA) in a feed premix. Four heifers received the labeled dose of 0.5 mg/day. Regular feces samples were taken throughout the experiment. A rapid screening method for the determination of MGA in feces was developed, consisting of liquid extraction, clean-up on solid-phase extraction cartridges and quantification by enzyme immunoassay (ELISA). Residues in feces were dose-dependent with mean values of < 0.25, 2.0, 4.4, or 15.4 ng/g for 0, 0.5, 1.5, and 5 mg/day doses, respectively. In contrast to urine analysis, feces analysis appeared to be a suitable means of non-invasive screening before slaughter for surveillance of MGA treatment and verification of its compliance with labeled dosage.     

上海地区多个肿瘤标志物正常参考值的初步确定

目的通过回顾分析初步建立上海地区健康人群多个肿瘤标志物的参考区间,可为临床应用肿瘤标志物提供依据。方法选择2012年3月至2013年4月期间在复旦大学附属华山医院进行健康体检样本共计604例,采用流式荧光发光法检测血清中甲胎蛋白（AFP）、糖类抗原125（CA125）、细胞角蛋白19片段（CYFRA21-1）癌胚抗原（CEA）、神经元烯醇化酶（NSE）、糖类抗原19-9（CA19-9）、总前列腺特异性抗原（tPSA）浓度值,对浓度值做统计分析。结果 AFP参考值：男性〈10.32ng/mL,女性〈8.12ng/mL;CA125参考值：〈27.02U/mL;CEA参考值：男性〈4.3ng/mL,女性〈3.74ng/mL;NSE参考值：女性青年组（〈45岁）〈11.64ng/mL,女性中老年组（≥45岁）〈15.20ng/mL,男性青年组（〈45岁）〈18.47ng/mL,男性中老年组（45岁）〈20.04ng/mL;CA199参考值：〈20.73U/mL;tPSA参考值：〈1.48ng/mL。结论已经初步建立上海地区各个肿瘤标志物参考区间。     

The Effectiveness and Harms of Screening for Chronic Obstructive Pulmonary Disease: An Updated Systematic Review and Meta-Analysis

BackgroundThis study aimed to perform meta-analyses to update a previous systematic review (SR) conducted by the US Preventive Services Task Force (USPSTF) to evaluate the benefits and harms of screening for chronic obstructive pulmonary disease (COPD) in asymptomatic adults.MethodsMEDLINE, EMBASE, Cochrane Library, and regional databases were searched from their inception to January 2020. Studies for diagnostic accuracy, preventive services effect, treatment efficacy, and treatment harms were included.ResultsEighteen studies were included, and twelve of these were newly added in this update. In meta-analyses, the pooled sensitivity and specificity for COPD diagnosis using spirometry were 73.4% and 89.0%, respectively. The relative effect of smoking cessation intervention with screening spirometry, presented as abstinence rate, was not statistically significant (risk ratio [RR], 1.21; 95% confidence interval [CI], 0.87–1.67) when all selected studies were pooled, but screening on smoking cessation was effective (RR, 1.58; 95% CI, 1.14–2.19) when limited to studies with smoking cessation programs that provided smoking cessation medicines or intensive counseling at public health centers or medical institutions.ConclusionIn this study, no direct evidence for the impact on health outcomes of screening asymptomatic adults for COPD was identified similar to the previous SR. Further research is necessary to confirm the benefits of COPD screening.     

人线粒体DNA荧光定量PCR检测方法的建立

建立SYBR Green I实时荧光PCR定量检测人线粒体DNA的方法。选取人线粒体DNA高度保守基因片段,将该基因片段与pCF-T载体连接后,转化入E.coli DH5α,提取重组质粒PCR及测序鉴定后,作为阳性模板建立SYBR-Green I荧光定量PCR标准曲线和熔解曲线。结果表明:构建的标准曲线线性关系良好(反应体系中含101~108拷贝时,扩增反应CT值与拷贝数的对数成线性关系),相关系数为0.997。批内和批间重复性测定的变异系数分别为1.23%~3.29%以及3.10%~5.21%。我们成功建立了实时荧光定量PCR检测人线粒体DNA的方法,该方法可作为进一步研究线粒体DNA的方法,在相关疾病诊断和监测中具有一定的应用前景。     

Establishment of Reference Ranges for Prostate Volume and Annual Prostate Volume Change Rate in Korean Adult Men: Analyses of a Nationwide Screening Population

We aimed to determine normal reference ranges for prostate volume (PV) and annual PV change rate in a Korean nationwide screening population. Data from men who underwent a routine health check-up were collected from 13 university hospitals. The cohort comprised men aged ≥40 yr who had undergone 2 or more serial transrectal ultrasonographies. Men with initial PV>100 mL; serum PSA level>10 ng/mL; PV reduction>20% compared with initial PV, or who had history of prostate cancer or prostate surgery, were excluded. Linear regression and mixed effects regression analyses were used to predict mean PV and longitudinal change in PV over time. A total of 2,967 men formed the study cohort. Age, body mass index (BMI), and serum prostate-specific antigen (PSA) level were found to be significant predictors of PV. A predicted PV table, with a 95% confidence interval (CIs), was developed after adjusting for these 3 variables. Annual PV change rate was 0.51 mL/year (95% CI, 0.47-0.55). Annual PV change rate according to age was 0.68 mL/year, 0.84 mL/year, 1.09 mL/year, and 0.50 mL/year for subjects in their 40s, 50s, 60s, and ≥70 yr, respectively. Predicted annual PV change rate differed depending on age, BMI, serum PSA level and baseline PV. From a nationwide screening database, we established age-, PSA-, and BMI-specific reference ranges for PV and annual PV change rate in Korean men. Our newly established reference ranges for PV and annual PV change rate will be valuable in interpreting PV data in Korean men.

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