Clinical and molecular findings in children with complex I deficiency

Isolated complex I deficiency, the most frequent OXPHOS disorder in infants and children, is genetically heterogeneous. Mutations have been found in seven mitochondrial DNA (mtDNA) and eight nuclear DNA encoded subunits, respectively, but in most of the cases the genetic basis of the biochemical defect is unknown. We analyzed the entire mtDNA and 11 nuclear encoded complex I subunits in 23 isolated complex I-deficient children, classified into five clinical groups: Leigh syndrome, progressive leukoencephalopathy, neonatal cardiomyopathy, severe infantile lactic acidosis, and a miscellaneous group of unspecified encephalomyopathies. A genetic definition was reached in eight patients (35%). Mutations in mtDNA were found in six out of eight children with Leigh syndrome, indicating a prevalent association between this phenotype and abnormalities in ND genes. In two patients with leukoencephalopathy, homozygous mutations were detected in two different nuclear-encoded complex I genes, including a novel transition in NDUFS1 subunit. In addition to these, a child affected by mitochondrial encephalomyopathy had heterozygous mutations in NDUFA8 and NDUFS2 genes, while another child with neonatal cardiomyopathy had a complex rearrangement in a single NDUFS7 allele. The latter cases suggest the possibility of unconventional patterns of inheritance in complex I defects.     

PCT、IL-6及CRP对新生儿宫内细菌感染的诊断价值

目的:探讨新生儿宫内细菌感染采用降钙素原(PCT)、白细胞介素-6(IL-6)、及C反应蛋白(CRP)诊断的临床价值。方法:根据感染结局将2013年3月~2014年9月在我院分娩且有宫内感染高危因素的179例新生儿分为感染组(34例)和无感染组(145例),检测两组的PCT、IL-6及CRP水平,并比较各项指标对宫内细菌感染的诊断价值。结果:感染组脐带血PCT、IL-6、CRP水平均高于无感染组,差异有统计学意义(P0.05)。感染组各单个指标阳性率、两指标联合的阳性率高于无感染组,差异均有统计学意义(P0.05),感染组中PCT、IL-6阳性率高于CRP,PCT+IL-6的阳性率高于PCT+CRP、IL-6+CRP,差异均有统计学意义(P0.05)。PCT+IL-6的灵敏度、准确率高于单个指标及其他两个指标联合检测的结果,差异有统计学意义(P0.05),各项指标检测的特异性比较,差异无统计学意义(P0.05)。结论:新生儿宫内感染采用脐带血PCT检测具有灵敏度高,特异性好的特点,联合IL-6检测是临床诊断新生儿宫内感染的最有效的方式。     

Chromosome translocations: study of 232 cases originating from 144 families

Between 1974 and 1987, 232 translocation carriers have been detected in our Center; they belong to 144 different families. Indications for chromosome analysis were the following: familial studies in relation with a patient suggesting a chromosome anomaly (25.4%); mental retardation with or without malformations (24.6%); 2 or more spontaneous abortions (17.2%); infertility problems, mainly male (16.4%); genetic counseling for a non-chromosomal disease (9.5%); prenatal diagnosis in risk pregnancies (6.9%). The chromosome anomalies detected were the following; balanced Robertsonian fusions (114 cases = 49.1%); balanced translocations (74 cases = 31.9%); unbalanced translocations, Robertsonian fusions included (44 cases = 19%). Two groups may be distinguished: the first one confirms data already known, such as high frequency of balanced translocations in couples with multiple abortions, or in infertile males. The second group on the contrary shows more unusual observations: 4 cases of standard trisomy 21 born to young parents carriers of a balanced translocation not involving chromosome 21; 5 cases of trisomy 13 with 46 chromosomes and a Robertsonian fusion, born to parents carriers of a t(13q; Dq) (twice the mother and thrice the father); 14 cases of apparently balanced translocations, however with an abnormal phenotype; and finally 22 cases of balanced translocations incidentally detected during the course of investigations in patients with a genetic problem generally not associated with a chromosome defect.     

脑苷肌肽对新生儿缺氧缺血性脑病的临床疗效及安全性评价

目的:探究脑苷肌肽对新生儿缺氧缺血性脑病的临床疗效及安全性。方法:收集我院收治的缺氧缺血性脑病患儿61例,根据治疗方法不同分为实验组与对照组,实验组31例采用脑苷肌肽治疗,对照组30例采用胞二磷胆碱治疗。观察并比较两组患儿的治疗效果及不良反应情况。结果:治疗后,两组患儿惊厥、嗜睡以及过度兴奋等神经症状均逐渐消失,且实验组明显早于对照组,差异具有统计学意义(P0.05);与治疗前相比,两组治疗后行为能力、肌张力、原始反应以及意识状态水平均明显升高,且治疗10-14天后,实验组新生儿行为学评分显著高于对照组,差异具有统计学意义(P0.05);两组不良反应比较,差异无统计学意义(P0.05)。结论:脑苷肌肽治疗新生儿缺氧缺血性脑病可有效减轻缺血所致的神经功能障碍,加速神经损伤恢复,临床疗效显著,且安全性较高。     

肺超声评分在预测新生儿肺不张疾病中的临床价值

摘要 目的：探讨肺超声评分在预测新生儿肺不张疾病中的临床价值。方法：2018年3月到2021年4月选择在本院新生儿重症监护病房(neonatal intensive care unit，NICU)诊治的83例新生儿肺不张疾病作为肺不张组，同期选择在本院出生的无呼吸系统疾病新生儿83例作为对照组，所有新生儿都给予肺超声，记录超声特征并进行肺超声评分，判断肺超声诊断价值与预测预测新生儿肺不张疾病的效果。结果：肺不张组的肺超声评分高于对照组(P<0.05)。在166例新生儿中，肺超声判断为肺不张82例，肺超声诊断新生儿肺不张疾病的敏感性与特异性分别为100.0%(82/82)和98.8%(83/84)。在166例新生儿中，Spearsman相关性分析显示新生儿肺不张疾病与肺超声评分存在相关性(r=0.633，P=0.000)。受试者工作特征(Receiver operating characteristics，ROC)曲线分析显示肺超声评分预测新生儿肺不张疾病肺炎曲线下面积(Area under the curve，AUC)为0.888(95%CI=1.472-3.572)。新生儿肺不张疾病在肺超声上主要表现为胸膜线增厚并模糊，粗糙不平，A线存在，肺滑动征消失，多发典型B线与多发融合B线。结论：肺超声是简便、无放射性损伤、准确的检查方法，肺超声评分能有效预测新生儿肺不张疾病中的发生，也能提高对新生儿肺不张疾病的诊断效果。     

脑电图检查对新生儿缺氧缺血性脑病的早期诊断及预后判断价值

目的:探讨脑电图检查对新生儿缺氧缺血性脑病早期诊断及预后判断的临床意价值。方法:本研究所选研究对象为我院2011年3月至2014年3月住院的91例出生后一天内的窒息新生儿,对其行脑电图检查,根据脑电图的检查结果将其分为四组,分别为正常组、轻度异常组、中度异常组、重度异常组。对上述四组患儿进行随访,时间点为出生后3个月、6个月,采用婴幼儿发育量表对患儿的智能发育进行测评,对各组智能发育的差异进行比较。结果:(1)91例患儿中,脑电图异常的有83例,异常率为91.21%,脑电图的异常程度与临床分度基本一致;(2)对患儿随访至3个月时,轻度、中度、重度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,具有显著差异(P0.05);(3)对患儿随访至6个月时,轻度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,无显著差异(P0.05)。中度、重度异常组患儿的智力发育指数与运动发育指数的平均值与正常组患儿相比,具有显著差异(P0.05)。结论:早期脑电图检查结果对新生儿缺氧缺血性脑病的早期诊断有利,为临床上早期干预提供了重要的参考依据。     

Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.     

时间分辨荧光分析技术在先天性甲状腺功能低下筛查中的应用

目的:探讨时间分辨荧光分析技术(DELFIA)筛查新生儿先天性甲状腺功能低下的的准确率。方法:回顾性分析我院2008年1月至2013年5月收治的20000例新生儿的临床资料。分别利用酶联免疫吸附法(ELISA)和时间分辨荧光分析技术检测新生儿足跟血中三碘甲腺原氨酸(T3)、四碘甲腺原氨酸(T4)及促甲状腺素(TSH)水平。比较两种检测方法的准确率。结果:DELFIA初次筛查CH的准确性明显高于ELISA。对召回的新生儿进行TSH复测,DELFIA对TSH≥20 m U/L的检测准确率最高,差异具有统计学意义(P0.05)。结论:DELFIA在筛查先天性甲状腺功能低下中具有较高的应用价值,可作为临床筛查的首选方法。     

组织多普勒Tei指数对妊娠期糖尿病孕妇胎儿心功能的评估价值及母婴预后与血糖控制水平的关系研究

目的:探讨组织多普勒Tei指数对妊娠期糖尿病(GDM)孕妇胎儿心功能的评估价值,并分析母婴预后与血糖控制水平的关系。方法:选取2017年1月到2018年6月期间在我院行产前检查的GDM孕妇80例,根据血糖控制情况将其分为良好组(48例)和不良组(32例)。另选取同期在我院行产前检查的并在我院生产的健康孕妇50例作为对照组。比较三组研究对象的等容收缩时间(ICT)、等容舒张时间(IRT)、射血时间(ET)、Tei指数、妊娠结局以及新生儿并发症。结果:不良组的ET小于良好组和对照组,Tei指数大于良好组和对照组,差异均有统计学意义(P0.05),不良组的巨大儿、早产、羊水过多、胎儿窘迫的发生率高于良好组和对照组,差异均有统计学意义(P0.05),不良组的新生儿低血糖、高胆红素血症的发生率高于良好组和对照组,差异均有统计学意义(P0.05)。结论:组织多普勒Tei指数对GDM孕妇胎儿心功能具有较高的评估价值,可敏感地检测出胎儿心功能异常,血糖控制不良会明显增加不良妊娠结局和新生儿并发症的发生率。     

出生早期母婴分离对新生小鼠神经元细胞凋亡的影响

目的:探讨出生早期母婴分离对新生儿神经系统的影响及其相关机制。方法:随机选择2015年1月~2015年9月出生的新生小鼠120例作为本次研究的对象,其中新生小鼠出生后实施母婴分离的作为观察组(60只),出生后不实施母婴分离的作为对照组(60只)。比较两组新生小鼠的神经系统、神经细胞的变化。结果:观察组新生小鼠在母婴分离第7天、14天、21天的神经元细胞的凋亡率显著高于对照组新生(P值均0.05),神经元胱天蛋白酶-3(Caspase-3)蛋白表达均明显高于对照组(P值均0.05)。观察组新生小鼠的母婴分离14天、21天的神经胶质细胞小窝蛋白-1(Caveo-1)蛋白的表达,与对照组新生小鼠的神经胶质细胞Caveo-1蛋白的表达进行比较,(P值均0.05),具有统计学意义。结论:出生早期实施母婴分离,对新生儿的神经系统会产生较大的影响,影响新生儿发育中神经系统的表达,进而会影响新生儿成年后的行为发育异常。     

不同放散试验对新生儿ABO溶血病的诊断价值对比

摘要 目的：分析与比较不同放散试验对新生儿ABO溶血病的诊断价值。方法：选择2017年9月至2019年6月在本院进行ABO溶血病检测的新生儿240例,取所有新生儿的静脉血样本2~3 mL,采用冷冻复融放散试验方法与改良热放散试验方法检测新生儿ABO溶血病的发生情况,并比较单独诊断和联合诊断的价值。结果：在240份标本中,冷冻复融放散试验检出新生儿ABO溶血病阳性130例,阳性检出率为54.2 %;改良热放散试验检出新生儿ABO溶血病阳性94例,阳性检出率为39.2 %;二者联合检出新生儿ABO溶血病阳性100例,阳性检出率为41.67 %,联合检出新生儿ABO溶血病阳性率和冷冻复融放散试验检出新生儿ABO溶血病阳性率显著高于改良热放散试验检出新生儿ABO溶血病阳性率(P<0.05)。临床最终诊断为新生儿ABO溶血病101例,阳性率为42.08 %,患儿ABO血型包括A型56例,B型45例。冷冻复融放散试验诊断新生儿ABO溶血病的敏感性和特异性为73.8 %和95.5 % ,ROC曲线面积0.775;改良热放散试验检诊断为新生儿ABO溶血病的敏感性和特异性为100 %和95.2 %,ROC曲线面积0.853;二者联合诊断对新生儿ABO溶血病的敏感性和特异性为90.0 %和97.85 %,ROC曲线面积0.872,联合诊断特异性优于改良热放散试验检诊和冷冻复融放散试验诊断,且改良热放散试验检诊敏感性优于冷冻复融放散试验诊断。结论：相对于冷冻复融放散试验,改良热放散试验对新生儿ABO溶血病的诊断敏感性更高,且不影响诊断特异性,两种放散方法联合检测具有更好的应用价值。     

脐动脉血流对预测子痫前期新生儿和产妇结局的价值分析

目的:探讨应用脐动脉血流用于预测子痫前期新生儿和产妇结局的临床价值。方法:选择在我院产科建档分娩的120例孕产妇作为研究对象,根据子痫前期发病情况分为子痫前期组60例与对照组60例,记录和比较两组孕产妇的一般资料、血脂、血糖水平、分娩前脐动脉血流与新生儿体重、胎盘的重量及Apgar评分,并进行相关性与危险因素分析。结果:两组孕产妇的年龄、孕次、产次、流产次数、孕周等对比差异均无统计学意义(P0.05)。子痫前期组的血清HDL-C水平低于对照组(P0.05),血清TC、TG、LDL-C、FBG水平高于对照组(P0.05)。与对照组比较,子痫前期组脐动脉S/D、RI与PI值显著升高(P0.05)。所有孕产妇都顺利完成分娩,孕产妇与新生儿都存活,子痫前期组的新生儿出生体重及Apgar评分和胎盘的重量均显著低于对照组(P0.05)。在子痫前期组中,脐动脉S/D、RI、PI值与新生儿出生体重呈现显著负相关性(P0.05)。多重线性回归分析显示子痫前期孕产妇的脐动脉S/D、RI、PI值为影响新生儿出生体重的独立危险因素(P0.05)。结论:脐动脉血流与子痫前期新生儿出生体重显著相关,脐动脉S/D、RI、PI值为影响新生儿出生体重的独立危险因素,子痫前期脐动脉血流监测可为预测新生儿和产妇结局以及预后提供参考。     

Variable pleiotropic effects from mutations at the same locus hamper prediction of fitness from a fitness component

The relationship of genotype, fitness components, and fitness can be complicated by genetic effects such as pleiotropy and epistasis and by heterogeneous environments. However, because it is often difficult to measure genotype and fitness directly, fitness components are commonly used to estimate fitness without regard to genetic architecture. The small bacteriophage X174 enables direct evaluation of genetic and environmental effects on fitness components and fitness. We used 15 mutants to study mutation effects on attachment rate and fitness in six hosts. The mutants differed from our lab strain of X174 by only one or two amino acids in the major capsid protein (gpF, sites 101 and 102). The sites are variable in natural and experimentally evolved X174 populations and affect phage attachment rate. Within the limits of detection of our assays, all mutations were neutral or deleterious relative to the wild type; 11 mutants had decreased host range. While fitness was predictable from attachment rate in most cases, 3 mutants had rapid attachment but low fitness on most hosts. Thus, some mutations had a pleiotropic effect on a fitness component other than attachment rate. In addition, on one host most mutants had high attachment rate but decreased fitness, suggesting that pleiotropic effects also depended on host. The data highlight that even in this simple, well-characterized system, prediction of fitness from a fitness component depends on genetic architecture and environment.     

Calculation of the proportion of men excluded from paternity by HLA typing of the mother and child

When filiation research shows that paternity is possible, French legislation recommends the calculation of two coefficients: 1. paternity probability (CP); 2. percentage of random men excluded from paternity by genetic markers of the mother and the child (PEme). A method is proposed, allowing the determination of PEme for the HLA system and PEme for the various systems employed. The calculations, relatively simple, can be worked out quickly and without risk of error, using a computer. We successively look at simple cases, complex cases and unusual cases: maternal death, consanguinity problems, racial problems. HLA-A, B, C, DR, DQ typing almost always leads to the exclusion of more than 98% of innocent men (PEme greater than 0.98). The HLA system clearly appears to be the most conclusive of the systems utilized by experts.     

Locked patellar dislocation: a case report

Fertility is markedly reduced in patients with chronic renal failure. For women with pre-existing renal disease, pregnancy is associated with an increased rate of fetal complications and a considerable risk of renal disease progression. Due to substantial improvements in antenatal and neonatal care, fetal outcome has improved considerably in the last two decade. A Saudi survey which examined the frequency of pregnancy among women in end stage renal disease (ESRD) and undergoing regular hemodialysis (HD), showed an incidence of 7% over a five year period (1.4 per year). This may reflect the cultural endorsement of having offspring. We hereby report 2 cases of successful pregnancy managed at the Prince Salman Center for Kidney Diseases (PSCKD).     

200 例新生儿心脏彩超筛查先心病结果分析

目的:了解新生儿先天性心脏病(简称先心病)的发病情况,获得基本资料,为制定和采取干预措施提供决策依据。方法:将新生儿心脏彩超列入常规检查项目,选择西京医院产科2011年6月13日至7月23日出生的200名新生儿进行心脏彩超检查,筛查率为100%。结果:正常的为170例,占85%,其中需观察、随访的131例。异常的为30例,发病率占百分之15%,其中复杂先心病3例。30例先心病患儿中,以ASD+PDA类型心脏病最多,占56.67%;其次是ASD,占16.67%;VSD+PDA和VSD+PDA+PFO类型分别占6.67%;检出复杂先心病类型单室+房间隔缺损+肺动脉瓣狭窄、单房单室、部分型心内膜垫缺损+ASD+二尖瓣前瓣裂,分别占3.33%。结论:新生儿先心病的发病率较高,采用心脏彩超等检查项目筛查是非常必要的,需认识导致新生儿先心病的原因,尽早发现先心病患儿,并做好先心病患儿的随访工作,为及时进行干预提供保障。     

Pharmacological treatment of short-coupled idiopathic ventricular fibrillation: A review

Short-coupled idiopathic ventricular fibrillation (IVF) is a subtype of IVF in which episodes of polymorphic ventricular tachycardia or ventricular fibrillation are initiated by short-coupled premature ventricular contractions (PVCs). Our understanding of the pathophysiology is evolving, with evidence suggesting that these malignant PVCs originate from the Purkinje system. In most cases, the genetic underpinning has not been identified. Whereas the implantation of an implantable cardioverter-defibrillator is uncontroversial, the choice of pharmacological treatment is the subject of discussion. In this review, we summarize the available knowledge on pharmacological therapy in short-coupled IVF and provide our recommendations for management of patients with this syndrome.     

Incidence of trauma in a breeding and rearing colony of cynomolgus monkeys (Macaca fascicularis)

A statistical survey was performed in 1982 to ascertain the incidence of various diseases, especially trauma, in the cynomolgus monkey colony at Tsukuba Primate Center for Medical Science. In total, 1,029 cases of disease, occurred of which 866, 89 and 74 were surgical, internals and reproductive disease cases, respectively (Table 1). Among the 866 surgical cases, trauma (746 cases) was most often observed (Table 2). It was shown that trauma occurred most frequently during the group feeding of juvenile monkeys (Table 3). Analysis of the factors influencing the incidence of trauma during group feeding was carried out. As a result, it was revealed that the number of days after beginning group feeding and the age at which group feeding was begun had marked influences on the incidence of trauma (Figs. 1 and 2). However, there was no significant relationship between the incidence of trauma and the number of animals per group or the sex-ratio in a group (Tables 4 and 5). From the present survey results, a prospective rearing system should be established to reduce the incidence of trauma in the cynomolgus breeding and rearing colony.     

Fryns syndrome: another example of non-lethal outcome with severe mental handicap.

In this report we present clinical data of a patient with Fryns syndrome who survived the neonatal period. Two sibs died intra-uterine. The syndrome is characterized by craniofacial dysmorphism, diaphragmatic hernia and distal limb hypoplasia. Lethality in most cases is caused by the diaphragmatic hernia with concomitant lung hypoplasia. In patients with Fryns syndrome presenting without the diaphragmatic defect and lung-hypoplasia, survival beyond the neonatal period is possible; mental retardation is present in all four patients described so far. This report illustrates, once more, the great intrafamilial variation of the syndrome and emphasises its important consequences for genetic counseling and prenatal diagnosis.     

子宫动脉栓塞术在穿透性凶险性前置胎盘中的临床应用研究

目的:探讨子宫动脉栓塞术在穿透性凶险性前置胎盘中的临床应用效果。方法:选取2010年1月~2014年12月唐山市妇幼保健院收治的孕晩期穿透性凶险性前置胎盘患者36例,依据是否行子宫动脉栓塞术分为子宫动脉栓塞组20例和非子宫动脉栓塞组16例,比较两组患者的术中情况和临床结局。结果:子宫动脉栓塞组患者失血量、红细胞输血量、冷沉淀输血量均少于非子宫动脉栓塞组(P0.05)。两组患者血浆输血量和术后住院时间比较差异无统计学意义(P0.05)。子宫动脉栓塞组ICU入住率、子宫切除率、产后出血、DIC发生率均低于非子宫动脉栓塞组(P0.05)。两组患者的产褥感染率、失血性休克发生率、早产儿发生率以及新生儿轻度窒息率比较差异均无统计学意义(P0.05)。结论:子宫动脉栓塞术可以减少术中出血及术后并发症的发生率,改善穿透性凶险性前置胎盘的临床结局。