孤独症谱系障碍儿童早期神经发育水平和智能特征分析

目的:探讨孤独症谱系障碍(Autism spectrum disorder,ASD)儿童早期神经发育水平及智能分区特征,为提高ASD的早期识别和诊断提供理论依据.方法:运用Gesell发育评估量表对18月龄至48月龄以内的27例ASD患儿和30例发育迟缓(Mental retardation,MR)患儿的发育商(Dev...     

肠道菌群与孤独症谱系障碍儿童功能性便秘的关系

目的 探讨孤独症谱系障碍（autism spectrum disorder,ASD）儿童肠道菌群组成与功能性便秘之间的关系,为该类患者的治疗提供参考。方法 选择101例2～7岁ASD儿童和82例年龄、性别相匹配健康儿童为研究对象,采用罗马Ⅳ标准评估便秘,将所有儿童分为ASD便秘组（ASD constipated,AD-C）、ASD非便秘组（ASD non-constipated,AD-NC）、正常便秘组（neurotypical constipated,NT-C）、正常非便秘组（neurotypical non-constipated,NT-NC）。对所有粪便样本中细菌16S rRNA基因V3-V4高变区进行测序,检测肠道菌群。结果 与NT组相比,AD组儿童肠道菌群α多样性指数（Chao1）显著升高（t=2.258,P=0.006）,组间β多样性差异有统计学意义（R=0.210,P<0.001）。AD组儿童肠道优势菌群为双歧杆菌属、柯林斯菌属、脱硫弧菌属等。与NT-NC组相比,AD-NC组患儿肠道菌群Chao1指数显著升高（t=2.170,P=0.021）,组间β多样性差异有统计...     

孤独症谱系障碍动物模型研究进展

孤独症谱系障碍(austim spectrum disorder,ASD)近来全球发病率不断升高,但该病的病因及发病机制尚未明确,从动物模型出发探索疾病的病因及发病机制是必然趋势。国内对本病的认识及动物模型研究相对滞后,国际上ASD动物模型可大概分为基因遗传模型、特发性动物模型及调控环境因素动物模型三大类,其中基因遗传模型较多,但研究针对性过强;特发性模型中的BTBR模型及调控环境因素模型中的丙戊酸诱导模型能够较好地呈现ASD典型临床症状及部分病理学特征,为当前主要应用模型。ASD的研究尚缺乏完整符合结构有效性、表面有效性、预测有效性的理想动物模型。     

孤独症谱系障碍与胃肠道疾病研究进展

孤独症谱系障碍(autistic spectrum disorder,ASD)是指一系列的神经系统发育障碍,根据美国《精神障碍诊断和统计手册》(第五版)(DSM-5),其主要特征为社会交往和交流障碍、重复和刻板行为。随着对该疾病的深入了解,发现ASD儿童存在多系统的共患疾病,其中最常见的就是ASD儿童广泛存在的胃肠道症状(gastrointestinal issues,GI),如腹痛、腹泻、呕吐、慢性便秘和胃食管反流等。胃肠道疾病严重影响ASD儿童的饮食、睡眠和日常行为。事实上,部分ASD儿童的一些行为问题(如自我伤害、易激惹等)与胃肠道疾病有密切的关系。因此,ASD儿童的胃肠道疾病引起了父母和研究者越来越多的关注。同时,肠-脑轴的作用、肠道菌群失调可能造成的影响也受到关注。本文综述了ASD与胃肠道疾病的新近研究进展,介绍了ASD儿童胃肠道疾病的临床表现及其可能的原因,展望了通过治疗胃肠道疾病、调整肠道菌群对改善ASD儿童生理健康和行为症状的意义。     

孤独症谱系障碍动物模型相关神经生物学研究进展

孤独症谱系障碍(austim spectrum disorder, ASD)是一种以社交和沟通障碍以及重复和限制性行为为特征的神经发育障碍。ASD的表型异质性使得确定核心症状涉及的确切病因和病理生理机制困难重重,且这些症状通常伴有注意缺陷多动障碍、癫痫发作和感觉运动异常等共患病。动物模型提供了阐明疾病的病因和发病机制的重要平台。越来越多的研究利用如环境暴露、母体免疫激活(maternal immune activation, MIA)等诱导的动物模型进行孤独症谱系障碍病因病机的探讨以及药物治疗靶点的筛选。该文综述常见动物模型的不同神经网络机制、脑组织及相关因子变化、症状表型等方面,为今后进行精准动物实验研究提供针对性的动物模型选择,也可为阐明疾病神经生物学、开发潜在的治疗药物提供参考。     

基于心率检测的便携式儿童情绪感知系统研制

目的:检测儿童的情绪能力,从而检验儿童情绪能力发展是否正常以及协助训练孤独症儿童的情绪能力。方法:设计了一套便携式的儿童情绪感知系统,检测儿童的情绪能力。本系统由心率信号采集模块,PC机端的软件以及情绪能力数据分析组成。结果:研制的儿童情绪能力感知系统具有便携、可穿戴等优点,能够准确地检测儿童情绪能力。结论:儿童情绪能力感知系统能够检测使用者的情绪能力,也能够在儿童情绪能力干预训练中记录孤独症儿童的情绪变化,为干预训练提供帮助。     

神经元增殖与孤独症谱系障碍大脑过度生长

在患儿发育早期,某一亚类孤独症谱系障碍（autism spectrum disorders, ASDs）大脑呈过度生长趋势。研究发现,部分伴随有大脑过度增生的患者局部脑区神经元数目异常增多。进一步研究表明,神经元的增殖紊乱与局部脑区神经元数目异常增多密切相关。本综述从ASDs相关信号分子对神经元增殖的调控入手,归纳总结近年来基于神经元增殖调控异常的ASDs大脑过度增生的分子机制研究,为探究ASDs的发病机制提供一个重要的突破口。     

孤独症谱系障碍的遗传基础与神经机制

孤独症谱系障碍(autism spectrum disorder,ASD)是一种神经精神障碍,主要表现为社会交往障碍、交流障碍以及局限性的兴趣和重复刻板的行为模式三个主要核心症状．本文介绍了ASD的遗传基础和神经机制的最新研究进展．ASD具有较高的遗传率,且ASD个体的5-羟色胺和睾丸激素都较高．神经影像学研究发现,ASD个体的杏仁核、扣带回、梭状回、镜像神经元和前额叶等大脑区域在结构和功能上都与正常发育个体存在差异,但在个别区域激活模式的差异方向上仍存在不一致的地方．此外,功能连接的研究结果也证实了ASD个体连接不良的假设．未来的研究应该更多地着眼于如何利用这些基础研究成果为临床上提出有效的治疗和训练方式．     

孤独症谱系障碍小鼠肠道屏障功能研究

研究孤独症谱系障碍（ASD）模型小鼠肠道屏障功能及肠道动力的改变情况,为微生物−肠−脑轴在ASD发病中的作用提供理论基础。

C57bl/6J雌鼠和雄鼠交配,丙戊酸钠（VPA）诱导的ASD模型及对照组小鼠分别于孕12.5天皮下注射VPA或生理盐水。BTBR模型组为BTBR T⁺Itpr3^tf/J小鼠交配所产幼雄鼠。各组小鼠出生3周后,每窝随机选择2只雄鼠,各组5窝,共计10只,纳入相应组别。各组小鼠6周开始按如下顺序进行行为学检测：旷场实验、埋珠实验、三室社交实验、发声检测和自我梳理实验,各检测间隔5 d。评估小鼠肠道动力（粪便含水量及小肠推进率）和小鼠肠道屏障功能：FITC-葡聚糖灌胃后光谱仪检测小鼠血清中FITC-葡聚糖水平;Western blot检测各组小鼠结肠TREK1,CLDN1,CLDN3,OCLN及ZO1蛋白的表达;qPCR检测各组小鼠结肠Il6,Tnf-α和Ifn-γ mRNA的表达情况。

行为学检测结果显示：与对照组相比,BTBR组和VPA组小鼠穿越旷场中间区次数和停留时间显著降低（P＜0.05）;于目标小鼠侧室的停留时间率显著降低（P＜0.05）;埋珠率和自我梳理时间均显著升高（P＜0.05）;在（20～50）kHz和（50～100）kHz频率范围的发声次数及持续时间均显著降低（P＜0.05）。与对照组相比,BTBR组小鼠粪便含水量显著降低（P＜0.05）,而VPA组小鼠的差异无统计学意义（P＞0.05）。BTBR组和VPA组小鼠小肠推进率与对照组相比无差异（P＞0.05）。此外,与对照组相比,BTBR组和VPA组小鼠血清FITC−葡聚糖水平均升高,结肠TREK1,CLDN1,CLDN3,OCLD蛋白的表达水平降低,结肠Il6,Tnf-α和Ifn-γ mRNA的表达显著升高,差异均具有统计学意义（P＜0.05）,而ZO1的表达差异无统计学意义（P＞0.05）。

鉴于BTBR及VPA模型小鼠均表现出与ASD患者类似的广泛行为障碍,上述模型可作为ASD研究的可靠参考。与此同时,两种ASD小鼠模型均出现肠道紧密连接蛋白表达下调,肠道屏障通透性和促炎细胞因子水平的增高,表明微生物−肠−脑轴在ASD发病中扮演重要角色,且对治疗ASD症状具有潜在临床价值。

     

孤独症谱系障碍小鼠模型行为学检测方法

孤独症谱系障碍(autism spectrum disorder,ASD)是一种遗传相关的神经系统发育性疾病,患者主要呈现社交缺陷、沟通障碍、重复刻板行为和学习记忆障碍等核心症状.小鼠模型是探究孤独症谱系障碍的致病机理和寻找潜在治疗方法的重要工具,而小鼠行为学的观测和分析可以帮助人们更好地了解不同遗传操作对相应孤独症表...     

Prospective,Blinded Exploratory Evaluation of the PlayWisely Program in Children with Autism Spectrum Disorder

The purpose of the study was to explore a low-cost intervention that targets an increasingly common developmental disorder. The study was a blinded, exploratory evaluation of the PlayWisely program on autism symptoms and essential learning foundation skills (attention, recognition, and memory skills) in children with a diagnosis of autism, autism spectrum disorder (ASD), pervasive developmental disorder – not otherwise specified (PDD-NOS), and Asperger syndrome (AS). Eighteen children, 1 to 10 years of age, were evaluated using the Childhood Autism Rating Scale, Second Edition (CARS2); the PlayWisely Interactive Test of Attention, Recognition, and Memory Skills; Autism Treatment Evaluation Checklist (ATEC), and the Modified Checklist for Autism in Toddlers (M-CHAT). There were significant treatment effects for the PlayWisely measure on the Yellow Sets that examine recognition; Purple Sets that examine brain region agility and early memory skills; Blue Sets that examine phonemic awareness and recognition; and for the Total Sets, with a similar trend toward improvement in the Green Sets that examine perception and Red Sets that examine attention. No other measures reached statistical significance. The results suggest that PlayWisely can improve recognition, brain region agility, phonemic awareness, letter recognition, and early memory skills in ASD. It was observed by the parents, coaches, and study investigators that the children who were less than 3 years of age showed improvements in autism symptoms; however, the group was too small to reach statistical significance. Future studies are needed to see if this intervention can mitigate autism symptoms in very young children with ASD.     

核心稳定性训练对痉挛型脑性瘫痪患儿爬行能力及日常生活活动能力的影响

目的:研究核心稳定性训练(CST)对痉挛型脑性瘫痪(SCP)患儿爬行能力及日常生活活动能力的影响。方法:选择从2015年1月到2017年2月期间在我院接受治疗的SCP患儿134例纳入本次研究,根据随机数字表法将患儿分成观察组及对照组,各67例,对照组给予常规训练,观察组则给予CST,两组均治疗3个月。对比两组疗效、治疗前及治疗3个月后的爬行能力评分以及日常生活活动能力评分。结果:观察组的总有效率是95.52%,明显高于对照组的85.07%,差异有统计学意义(P0.05)。治疗3个月后两组的爬行能力评分均分别高于治疗前,且观察组高于对照组,差异均有统计学意义(均P0.05)。治疗3个月后两组的日常生活活动能力各项评分均分别高于治疗前,且观察组高于对照组,差异均有统计学意义(均P0.05)。结论:CST对SCP患儿的爬行能力及日常生活活动能力具有较好的改善作用,临床治疗过程中可应用此种训练措施强化患儿的运动功能,从而促进其获得更好的预后,值得给予推广。     

Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder

Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system—endogenous cannabinoids, their receptors and associated enzymes—in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg⁻¹, which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.     

支原体肺炎患儿细胞免疫功能及肺功能状态变化的临床研究

目的:研究支原体肺炎患儿细胞免疫及肺功能状态的变化情况。方法:选取2014年10月~2015年10月于本院进行诊治的68例支原体肺炎患儿为观察组,以同期68名体检健康儿童为对照组。观察并比较两组儿童的细胞免疫及肺功能,以及不同程度肺炎患儿的细胞免疫及肺功能指标。结果:观察组患儿细胞免疫指标及肺功能指标均低于对照组,差异具有统计学意义(P0.05);观察组重度肺炎患儿的细胞免疫指标及肺功能指标均低于中度及轻度患儿,差异具有统计学意义(P0.05);观察组中度肺炎患儿的细胞免疫指标及肺功能指标均低于轻度患儿,差异具有统计学意义(P0.05)。结论:支原体肺炎患儿细胞免疫及肺功能呈异常状态,且不同严重程度肺炎患儿的差异明显。     

羚羊角胶囊联合拉莫三嗪治疗小儿癫痫的临床研究

摘要 目的：观察羚羊角胶囊联合拉莫三嗪治疗小儿癫痫的治疗效果。方法：选取2018年1月~2021年1月期间来东营市人民医院就诊的小儿癫痫患儿100例,按照信封抽签法分为对照组（拉莫三嗪治疗）和研究组（羚羊角胶囊联合拉莫三嗪治疗）,各为50例,连续治疗12周。对比两组疗效,癫痫症状、自控能力、认知功能改善情况以及炎症因子和神经损伤指标变化,记录治疗不良反应。结果：与对照组76.00%的临床总有效率相比,研究组的94.00%明显更高（P<0.05）。研究组治疗后癫痫发作次数少于对照组,平均症状持续时间短于对照组（P<0.05）。研究组治疗后操作智商（PIQ）、言语智商（VIQ）和全智商（FIQ）评分高于对照组（P<0.05）。研究组治疗后血清神经元特异性烯醇化酶（NSE）、信号素3A（SEM3A）、白介素-2（IL-2）、肿瘤坏死因子-α（TNF-α）水平低于对照组（P<0.05）。两组患儿不良反应发生率组间对比无统计学差异（P>0.05）。结论：羚羊角胶囊联合拉莫三嗪治疗小儿癫痫,可提高患儿认知功能和自控能力,调节NSE、IL-2、S-100β、TNF-α水平,促进症状改善。     

Comparative two‐dimensional polyacrylamide gel electrophoresis of the salivary proteome of children with autism spectrum disorder

In the last decades, prevalence of autism spectrum disorder (ASD) has been on the rise. However, clear aetiology is still elusive and improvements in early diagnosis are needed. To uncover possible biomarkers present in ASD, we used two‐dimensional polyacrylamide gel electrophoresis and nanoliquid chromatography‐tandem mass spectrometry (nanoLC‐MS/MS), to compare salivary proteome profiling of children with ASD and controls. A total of 889 spots were compared and only those spots with a fold change ≥1.7 and a P‐value <0.05 or a fold change of ≥3.0 between ASD cases and controls were analysed by nanoLC‐MS/MS. Alpha‐amylase, CREB‐binding protein, p532, Transferrin, Zn alpha2 glycoprotein, Zymogen granule protein 16, cystatin D and plasminogen were down‐regulated in ASD. Increased expression of proto‐oncogene Frequently rearranged in advanced T‐cell lymphomas 1 (FRAT1), Kinesin family member 14, Integrin alpha6 subunit, growth hormone regulated TBC protein 1, parotid secretory protein, Prolactin‐inducible protein precursor, Mucin‐16, Ca binding protein migration inhibitory factor‐related protein 14 (MRP14) was observed in individuals with ASD. Many of the identified proteins have previously been linked to ASD or were proposed as risk factors of ASD at the genetic level. Some others are involved in pathological pathways implicated in ASD causality such as oxidative stress, lipid and cholesterol metabolism, immune system disturbances and inflammation. These data could contribute to protein signatures for ASD presence, risk and subtypes, and advance understanding of ASD cause as well as provide novel treatment targets for ASD.     

阿立哌唑结合心理行为疗法治疗儿童抽动障碍的疗效及对血流动力学的影响

摘要 目的：研究阿立哌唑结合心理行为疗法治疗儿童抽动障碍的疗效及对血流动力学的影响。方法：选取2018年1月～2020年1月我院收治的抽动障碍患儿80例,将所有患儿以随机数字表法分为对照组与研究组,每组各40例。对照组给予氟哌啶醇结合心理行为疗法治疗,研究组给予阿立哌唑结合心理行为疗法治疗,疗程均为10周。比较两组临床疗效,治疗前后患儿抽动障碍情况、血流动力学指标变化以及不良反应发生情况。结果：研究组总有效率为95.00%,高于对照组的77.50%（P＜0.05）。治疗后研究组发声性抽调、运动性抽动、行为以及运动不宁评分分别为（2.81±1.07）分、（1.94±0.45）分、（1.16±0.44）分、（0.82±0.50）分,均明显低于对照组的（4.71±0.73）分、（2.77±0.38）分、（1.57±0.39）分、（1.22±0.43）分（P＜0.05）。治疗前后两组心率（HR）、能量转换指数（MEC）、左心室机械效率（LME）以及心肌耗氧量（MVO）水平对比均无统计学差异（P＞0.05）。研究组不良反应发生率为7.50%,低于对照的25.00%（P＜0.05）。结论：阿立哌唑结合心理行为疗法治疗儿童抽动障碍疗效显著,可有效改善患儿临床症状,对血流动力学影响较小,具有较好的安全性。     

Further insight into the neurobehavioral pattern of children carrying the 2p16.3 heterozygous deletion involving NRXN1: Report of five new cases

Increasing evidence links heterozygosity for NRXN1 gene deletions to a clinically wide spectrum of neurodevelopmental, psychiatric, and neurological disorders. However, to date, the neurocognitive and social communication features of children carrying this genomic rearrangement have not been assessed in detail. The cognitive and behavioral profiles of five children carrying a heterozygous NRXN1 deletion were investigated through systematic assessment of the cognitive and developmental levels, adaptive profile and presence of behavioral symptoms and autistic features. Furthermore, four transmitting parents were assessed by means of cognitive, psychopathological and parental stress tests. A below‐average cognitive level was documented in all children, and defective adaptive levels were observed in four of them. Three of the five children were diagnosed as having autism spectrum disorder in comorbidity with intellectual disability/global developmental delay, with a major impairment in social communication skills. The remaining two children presented with isolated intellectual disability and an unclassifiable neurodevelopmental disorder, respectively. This study provide data contributing to a more accurate characterization of the neurobehavioral phenotype of individuals carrying heterozygous NRXN1 deletions. This analysis indicates that these structural rearrangements are associated with a variable expression of neuropsychiatric symptoms, and cast some doubts about the incomplete penetrance of the disorder.     

蒲地蓝配合揿针治疗小儿颈部淋巴结炎对CRP表达的影响

摘要 目的：探讨蒲地蓝配合揿针治疗小儿颈部淋巴结炎对C-反应蛋白(C-reactive protein,CRP)表达的影响。方法：2017年8月到2019年6月选择在本院诊治的小儿颈部淋巴结炎84例作为研究对象,根据随机数字表法把患儿分为联合组与对照组各42例。对照组给予蒲地蓝治疗,联合组给予蒲地蓝配合揿针治疗,疗程都为14 d,记录治疗效果与CRP表达变化情况。结果：治疗后联合组的总有效率为97.6 %,显著高于对照组的85.7 %(P<0.05)。联合组的局部消肿时间、局部压痛消退时间、发热消退时间都显著少于对照组(P<0.05)。两组治疗后的血清CRP值低于治疗前,联合组低于对照组,对比差异都有统计学意义(P<0.05)。两组治疗后的CD4⁺T淋巴细胞比例都高于治疗前,联合组高于对照组,对比差异都有统计学意义(P<0.05),两组治疗前后CD8⁺T淋巴细胞比例对比差异无统计学意义(P>0.05)。结论：蒲地蓝配合揿针治疗小儿颈部淋巴结炎能抑制CRP的释放,提高小儿的免疫功能,从而促进临床症状的消失,提高总体治疗效果。