Early-onset encephalomyopathy associated with tissue-specific mitochondrial DNA depletion: A morphological,biochemical and molecular-genetic study

A male infant, born from consanguineous parents, suffered from birth with a progressive neuromuscular disorder characterized by psychomotor delay, hypotonia, muscle weakness and wasting, deep-tendon areflexia and spastic posture. High levels of lactic acid in blood and cerebrospinal fluid suggested a mitochondrial respiratory chain defect. Muscle biopsy revealed raggedred and cytochromec oxidase-negative fibres, lipid accumulation and dystrophic changes. Multiple defects of respiratory complexes were detected in muscle homogenate, but cultured fibroblasts, myoblasts and myotubes were normal. Southern blot analysis showed markedly reduced levels of mitochondrial DNA (mtDNA) in muscle, while lymphocytes, fibroblasts and muscle precursor cells were normal. Neither depletion of mtDNA nor abnormalities of the respiratory complexes were observed in innervated muscle fibres cultured for as long as 4 months. No mutations were observed in two candidate nuclear genes,mtTFA andmtSSB, retro-transcribed, amplified and sequenced from the proband's mRNA. Sequence analysis of the mtDNA D-loop and of the origin of replication of the mtDNA light strand failed to identify potentially pathogenic mutations of these replicative elements in the proband's muscle mtDNA. Our findings indicate that mtDNA depletion is due to a nuclear encoded gene and suggest that the abnormality underlying defective mtDNA propagation must occur after muscle differentiation in vivo.     

Automatic classification of gait in children with early-onset ataxia or developmental coordination disorder and controls using inertial sensors

Early-Onset Ataxia (EOA) and Developmental Coordination Disorder (DCD) are two conditions that affect coordination in children. Phenotypic identification of impaired coordination plays an important role in their diagnosis. Gait is one of the tests included in rating scales that can be used to assess motor coordination.A practical problem is that the resemblance between EOA and DCD symptoms can hamper their diagnosis. In this study we employed inertial sensors and a supervised classifier to obtain an automatic classification of the condition of participants. Data from shank and waist mounted inertial measurement units were used to extract features during gait in children diagnosed with EOA or DCD and age-matched controls. We defined a set of features from the recorded signals and we obtained the optimal features for classification using a backward sequential approach. We correctly classified 80.0%, 85.7%, and 70.0% of the control, DCD and EOA children, respectively. Overall, the automatic classifier correctly classified 78.4% of the participants, which is slightly better than the phenotypic assessment of gait by two pediatric neurologists (73.0%). These results demonstrate that automatic classification employing signals from inertial sensors obtained during gait maybe used as a support tool in the differential diagnosis of EOA and DCD. Furthermore, future extension of the classifier’s test domains may help to further improve the diagnostic accuracy of pediatric coordination impairment. In this sense, this study may provide a first step towards incorporating a clinically objective and viable biomarker for identification of EOA and DCD.     

早发癫(痫)性脑病的研究进展

早发癫(痫)性脑病(early-onset epileptic encephalopathy,EEE)是指一组在新生儿期或婴儿期起病的严重癫(痫)综合征,为药物难治性全面或局灶发作性癫(痫),脑电图存在频繁而广泛的异常放电,常伴随严重发育迟缓和行为异常.发作间期脑电图改变具有年龄依赖性,并与智力运动发育落后密切相关.EEE主要包括早期肌阵挛脑病、大田原综合征、婴儿严重游走性局灶性癫(痫)、婴儿痉挛症及Dravet综合征.EEE的病因具有异质性,多数仍不明确,对多种抗癫(痫)药物及非药物疗法反应欠佳.EEE预后不良,多数患儿遗留有严重智力运动发育落后,部分甚至存在猝死的风险.     

早发型败血症早产儿脐血培养价值研究

背景　新生儿败血症是导致早产儿死亡的主要原因之一,尤其是早发型败血症（EOS）,因此早诊断、及时治疗尤为重要。血培养是诊断败血症的金标准,但新生儿外周血采血量有限,而脐血作为新生儿出生后最早的血液标本,血量充分,且收集方便。目的　探讨EOS早产儿脐血培养的临床应用价值,同时观察脐血培养阳性患儿炎性指标变化,以期为EOS的临床治疗提供依据。方法　选取天津医科大学第二医院2018年6月-2019年6月疑似或确诊宫内感染的产妇及其早产儿（胎龄≤37周）共150对,其中102例早产儿诊断为EOS,48例早产儿未诊断为EOS。于早产儿出生后即刻留取脐血,出生后24 h内留取外周静脉血,行血培养。分别于EOS患儿出生后0~<24、24~<48、48~72 h检测炎性指标〔超敏C反应蛋白（hs-CRP）、降钙素原（PCT）、白细胞计数（WBC）、血小板计数（PLT）〕,比较脐血培养阳性与脐血培养阴性EOS患儿不同时间炎性指标。EOS患儿脐血、外周血培养报警阳性后,进行脐血、外周血细菌鉴定。结果　EOS患儿脐血培养阳性率〔19.6%（20/102）〕与外周血培养阳性率〔16.7%（17/102）〕比较,差异无统计学意义（P>0.05）。非EOS患儿脐血、外周血培养阳性率均为0。脐血培养阳性EOS患儿出生后0~<24、24~<48、48~72 h hs-CRP、PCT高于脐血培养阴性EOS患儿（P<0.05）;脐血培养阳性EOS患儿出生后0~<24 h WBC低于脐血培养阴性EOS患儿（P<0.05）;脐血培养阳性EOS患儿出生后48~72 h PLT低于脐血培养阴性EOS患儿（P<0.05）。EOS患儿脐血培养共鉴定出20株致病菌,其中革兰阳性菌15株（包括葡萄球菌10株、单核细胞增生李斯特菌3株、无乳链球菌2株）,革兰阴性菌5株（包括大肠埃希菌3株、肺炎克雷伯菌肺炎亚种1株、鲍曼不动杆菌1株）。EOS患儿外周血培养共鉴定出17株致病菌,其中15例患儿外周血培养鉴定结果与脐血培养鉴定结果一致。结论　EOS患儿脐血培养阳性率与外周血培养阳性率相似,但脐血取血方便,留血量充分,有利于进行EOS的诊断。新生儿出生后若hs-CRP、PCT升高,WBC、PLT降低,提示可能存在EOS,可酌情调整抗生素用药,并依据细菌培养结果及时确定抗感染疗程及进一步诊治方案。     

Early- and late-onset pancreatic adenocarcinoma: A population-based comparative study

BackgroundPancreatic cancer is projected to become the second leading cause of cancer related death in the US. We aim to investigate the demographics, clinical outcomes and survival outcomes of patients diagnosed with early-onset (<40 years) and late-onset (>40 years) pancreatic adenocarcinoma (PAC).MethodsData on PAC between 1975 and 2016 were extracted from the Surveillance, Epidemiology, and End Results Registry.ResultsWithin the study period, 136,100 patients were identified which included 1181 patients with early-onset PAC and 134,919 patients with late-onset PAC. Both cohorts tend to present with distant metastasis (70.3% vs 57.9%). Both groups also showed an exponential rise in incidence (early-onset 3.69% annual change vs late-onset 6.25% annual change). When stratified by anatomical location, there was a trend of increasing cancer in the head of the pancreas for patients <40 years (3.63% annual change). While late PAC showed increasing cancer in all anatomical locations, the largest increase was observed in the tail of the pancreas (8.62% annual change). Overall, there was a mild difference in survival for early- and late-onset PAC (7 months vs 6 months, respectively, log rank p = 0.004). Both age groups showed the worse prognosis when cancer occurred in the tail of the pancreas (6 months vs 4 months, respectively). On cox proportion analysis, patients with late-onset PAC had twice the risk of mortality compared to early-onset PAC (HR 2.06, CI: 1.788–2.370, P = 0.001).ConclusionsOur study showed that both early- and late-onset PAC are increasing and while prognosis remains poor. Tumor anatomy showed a growing incidence of early-onset PAC in the head of the pancreas while late-onset PAC showed a rising incidence in the body and tail of the pancreas.     

一次性声门下吸引器降低早发呼吸机相关性肺炎的效果观察

目的调查一次性声门下吸引器在气管切开使用声门下吸引的气管套管、机械通气患者中的临床使用效果,以降低早发呼吸机相关性肺炎(VAP)的发生。方法将2012年1-12月入住ICU、行气管切开使用带声门下吸引的气管套管并机械通气的46例患者作为研究对象,按随机数字表分为对照组(常规吸引组)和观察组(一次性声门下吸引器组)各23例,观察比较两组的早发VAP发生率及吸引量,数据采用SPSS13.0统计软件进行分析。结果早发VAP发生率观察组为13.04%、对照组39.13%,两组比较差异有统计学意义(P<0.05);机械通气时间、住ICU时间及抗菌药物使用天数观察组为(8.29±4.26)、(22.10±12.903)、(6.73±1.78)d,对照组为(10.95±4.75)、(32.38±17.4)、(9.35±2.21)d,两组差异均有统计学意义(P<0.05);住院费用观察组较对照组有减少的趋势,但差异无统计学意义;观察组患者每日声门下吸引量较对照组明显增多,差异有统计学意义(P<0.05)。结论一次性声门下吸引器在临床使用中具有良好的效果,能降低早发VAP的发生。     

早发性脊柱侧凸生长棒治疗技术的研究进展

早发性脊柱侧凸的矫形治疗是世界性难题,近年来随着生长棒技术的临床应用及发展,为脊柱侧凸的矫形开辟了一条新途径.本文回顾生长棒在治疗早发性脊柱侧凸的发展历程并进行综述.     

Novel APP K724M mutation causes Chinese early-onset familial Alzheimer's disease and increases amyloid-β42 to amyloid-β40 ratio

Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly individuals. Although there are several million cases of AD estimated in China with the most population in the world, no Chinese early-onset familial AD caused by new APP gene mutation has ever been reported. Here, we first described a Chinese family with early-onset AD that was inherited in autosomal dominant manner, and the age of onset was 46.6 ± 7.7 years (n = 5; range, 40–58 years). By using genetic analysis of 3 collected patients' DNA samples, we identified a heterozygous APP gene mutation (g.275363A>T, K724M according to APP770). Finally, when APP695 with K724M mutation was ectopically expressed in HEK293 cell, the ratio of amyloid-β42 to amyloid-β40 was 2.23-fold higher than that of wild-type control. Together, our data suggest that APP K724M gene mutation may contribute to the cause of this Chinese early-onset familial AD.     

1990—2019年中国人群早发性结直肠癌疾病负担及变化趋势分析

目的 分析1990—2019年我国早发结直肠癌(early-onset colorectal cancer, EOCRC)疾病负担及时间变化趋势。方法 利用全球疾病负担2019(Global Burden of Disease 2019,GBD 2019)数据库获取我国14～49岁人群1990—2019年间结直肠癌发病、死亡及伤残调整寿命年(disability-adjusted life years, DALYs)的数量和率,以及危险因素所致EOCRC相关DALYs百分比。计算年龄标化发病率(age-standardized incidence rate, ASIR)及死亡率(age-standardized mortality rate, ASMR),并用Joinpoint软件对我国EOCRC的ASIR及ASMR行时间变化趋势分析。结果 2019年我国EOCRC新发病例及死亡人数为87 383及26 274,相比1990年分别增加264.53%及76.92%。我国EOCRC的ASIR及ASMR为10.31/10万及3.07/10万,较1990年分别增加140.32%及14.13%。...