neurological development

神经发育
  • 文章类型: Journal Article
    粒径≤2.5μm(PM2.5)的颗粒物是一种严重的环境威胁,极大地加剧了全球疾病负担。然而,伴随着该领域的快速研究进展,现有的发育毒性研究仍然受到有限数据来源的限制,不同的质量,不够深入的机理分析。该综述包括当前可用的流行病学和实验室证据,并全面描述了PM2.5对不同地区和各种污染源的发展中个体的不利影响。此外,这篇综述探讨了PM2.5暴露对不同种族个体的影响,性别,和社会经济水平对不良分娩结局以及心肺和神经发育的影响。此外,PM2.5对健康有害影响的分子机制主要包括转录和翻译调控,氧化应激,炎症反应,和表观遗传调节。研究了有关公共卫生与PM2.5之间关联的主要发现和新颖观点,强调未来研究探索其来源的必要性,composition,和特定性别的影响。此外,需要进一步的研究来更深入地研究更复杂的潜在机制,以有效地防止或减轻空气污染对人类健康的有害影响。
    Particulate matter of size ≤ 2.5 μm (PM2.5) is a critical environmental threat that considerably contributes to the global disease burden. However, accompanied by the rapid research progress in this field, the existing research on developmental toxicity is still constrained by limited data sources, varying quality, and insufficient in-depth mechanistic analysis. This review includes the currently available epidemiological and laboratory evidence and comprehensively characterizes the adverse effects of PM2.5 on developing individuals in different regions and various pollution sources. In addition, this review explores the effect of PM2.5 exposure to individuals of different ethnicities, genders, and socioeconomic levels on adverse birth outcomes and cardiopulmonary and neurological development. Furthermore, the molecular mechanisms involved in the adverse health effects of PM2.5 primarily encompass transcriptional and translational regulation, oxidative stress, inflammatory response, and epigenetic modulation. The primary findings and novel perspectives regarding the association between public health and PM2.5 were examined, highlighting the need for future studies to explore its sources, composition, and sex-specific effects. Additionally, further research is required to delve deeper into the more intricate underlying mechanisms to effectively prevent or mitigate the harmful effects of air pollution on human health.
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  • 文章类型: English Abstract
    OBJECTIVE: To investigate the impact of the environmental layout of the neonatal intensive care unit (NICU) on clinical outcomes and neurological development in very/extremely preterm infants.
    METHODS: A total of 304 very/extremely preterm infants admitted to Children\'s Hospital of Chongqing Medical University between January 2021 and June 2022 within 24 hours after birth were included in this retrospective cohort study. Based on different environmental layouts in the NICU, the infants were divided into two groups: centralized layout group (n=157) and decentralized layout group (n=147). The clinical outcomes and Test of Infant Motor Performance (TIMP) scores at corrected gestational age between 34 to 51+6 weeks were compared between the two groups.
    RESULTS: The decentralized layout group had lower incidence rates of bronchopulmonary dysplasia (44.9% vs 62.4%, P<0.05) and intracranial hemorrhage (17.7% vs 28.0%, P<0.05) than the centralized layout group. The cure rate was higher in the decentralized layout group compared to the centralized layout group (68.7% vs 56.7%, P<0.05). The decentralized layout group had higher TIMP scores than the centralized layout group at corrected gestational age between 34 to 51+6 weeks (P<0.05).
    CONCLUSIONS: The decentralized layout of the NICU exhibits positive effects on the clinical outcomes and early neurological development compared to the centralized layout in very/extremely preterm infants.
    目的: 探讨新生儿重症监护室(neonatal intensive care unit,NICU)环境布局对极/超早产儿临床结局及神经发育的影响。方法: 选取重庆医科大学附属儿童医院2021年1月—2022年6月收治、生后24 h内入院的304例极/超早产儿为研究对象。采用回顾性队列研究方法,根据NICU不同环境布局将患儿分为两组,即集中式布局组(157例)和分散式布局组(147例),比较两组患儿临床结局和校正胎龄34~51+6周时婴儿运动表现测试评分结果。结果: 分散式布局组支气管肺发育不良(44.9% vs 62.4%)和颅内出血(17.7% vs 28.0%)的发生率低于集中式布局组(均P<0.05);分散式布局组治愈率高于集中式布局组(68.7% vs 56.7%,P<0.05)。在校正胎龄34~51+6周时,分散式布局组婴儿运动表现测试评分高于集中式布局组(P<0.05)。结论: NICU分散式环境布局较集中式布局在极/超早产儿临床结局及早期神经发育方面显示出积极的影响。.
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  • 文章类型: Journal Article
    银纳米颗粒(AgNP)被广泛用作涂层材料。然而,AgNP对人类健康的潜在风险,尤其是神经和血管系统,仍然知之甚少。
    使用荧光显微镜检查了斑马鱼中各种浓度的AgNP的血管和神经毒性。此外,进行了Illumina高通量全球转录组分析,以探索斑马鱼胚胎暴露于AgNP后的转录组特征。进行京都基因和基因组百科全书(KEGG)富集分析以阐明AgNP暴露组和对照组之间的前3000个差异表达基因(DEG)。
    我们系统地研究了斑马鱼AgNP暴露对神经和血管发育的毒性。结果表明,AgNP暴露可引起神经发育异常,包括小眼睛表型,神经元形态缺陷,和抑制运动能力。此外,我们发现AgNP暴露诱导斑马鱼胚胎血管生成畸形。进一步的RNA-seq显示,在AgNP处理的斑马鱼胚胎中,DEGs主要富集在神经活性配体-受体相互作用和血管内皮生长因子(Vegf)信号通路中。具体来说,神经活性配体-受体相互作用通路和Vegf信号通路相关基因的mRNA水平,包括si:ch73-55i23.1,nfatc2a,prkcg,si:ch211-132p1.2,lepa,mchr1b,pla2g4aa,rac1b,p2ry6、adrb2、chrnb1和chrm1b,在AgNP处理的斑马鱼胚胎中受到显着调控。
    我们的发现表明,AgNP暴露通过干扰斑马鱼胚胎中的神经活性配体-受体相互作用和Vegf信号通路,在神经和血管发育中转录诱导发育毒性。
    UNASSIGNED: Silver nanoparticles (AgNP) are widely used as coating materials. However, the potential risks of AgNP to human health, especially for neural and vascular systems, are still poorly understood.
    UNASSIGNED: The vascular and neurotoxicity of various concentrations of AgNP in zebrafish were examined using fluorescence microscopy. In addition, Illumina high-throughput global transcriptome analysis was performed to explore the transcriptome profiles of zebrafish embryos after exposure to AgNP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to elucidate the top 3000 differentially expressed genes (DEGs) between AgNP-exposed and control groups.
    UNASSIGNED: We systematically investigated the neural and vascular developmental toxicities of AgNP exposure in zebrafish. The results demonstrated that AgNP exposure could cause neurodevelopmental anomalies, including a small-eye phenotype, neuronal morphology defects, and inhibition of athletic abilities. In addition, we found that AgNP exposure induces angiogenesis malformation in zebrafish embryos. Further RNA-seq revealed that DEGs were mainly enriched in the neuroactive ligand-receptor interaction and vascular endothelial growth factor (Vegf) signaling pathways in AgNP-treated zebrafish embryos. Specifically, the mRNA levels of the neuroactive ligand-receptor interaction pathway and Vegf signaling pathway-related genes, including si:ch73-55i23.1, nfatc2a, prkcg, si:ch211-132p1.2, lepa, mchr1b, pla2g4aa, rac1b, p2ry6, adrb2, chrnb1, and chrm1b, were significantly regulated in AgNP-treated zebrafish embryos.
    UNASSIGNED: Our findings indicate that AgNP exposure transcriptionally induces developmental toxicity in neural and vascular development by disturbing neuroactive ligand-receptor interactions and the Vegf signaling pathway in zebrafish embryos.
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  • 文章类型: Journal Article
    人类大脑生理学的研究,包括正常和疾病条件下的细胞相互作用,由于其复杂性和不可用性,一直是一个挑战。诱导多能干细胞(iPSC)研究在神经系统疾病的病理生理学研究中是不可或缺的。然而,单层系统缺乏细胞相互作用和神经系统疾病建模所需的细胞结构。由人类多能干细胞产生的脑类器官为模拟人类大脑的细胞相互作用和病理生理学提供了理想的环境。这篇综述文章讨论了脑类器官中神经谱系和非中枢神经系统细胞类型之间的组成和相互作用,目前的研究,以及大脑类器官研究的未来前景。最终,大脑类器官的前景是揭示复杂细胞相互作用产生的神经生物学以前无法接近的特征,并提高我们对神经发育和疾病的机械理解。
    The study of human brain physiology, including cellular interactions in normal and disease conditions, has been a challenge due to its complexity and unavailability. Induced pluripotent stem cell (iPSC) study is indispensable in the study of the pathophysiology of neurological disorders. Nevertheless, monolayer systems lack the cytoarchitecture necessary for cellular interactions and neurological disease modeling. Brain organoids generated from human pluripotent stem cells supply an ideal environment to model both cellular interactions and pathophysiology of the human brain. This review article discusses the composition and interactions among neural lineage and non-central nervous system cell types in brain organoids, current studies, and future perspectives in brain organoid research. Ultimately, the promise of brain organoids is to unveil previously inaccessible features of neurobiology that emerge from complex cellular interactions and to improve our mechanistic understanding of neural development and diseases.
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  • 文章类型: Journal Article
    我们前瞻性调查了在妊娠晚期接受替比夫定(LdT)治疗的母亲出生的婴儿的神经发育,以预防乙型肝炎病毒(HBV)母婴传播。高HBV载量的母亲被分配到LdT组(n=81,从妊娠第28周到分娩每天600mgLdT)或对照组(n=39,未经治疗)。使用Gesell发育计划工具对其婴儿进行36个月的随访,以评估身体和神经系统的发育。出生后12个月,LDT组粗大运动的平均得分,精细电机,适应性,语言学,个人社交领域与对照组相似。36个月时,LdT组的婴儿粗大运动平均得分高于对照组(98.42±9.69vs.94.54±7.48,P=0.03)。在LDT组中,粗大运动的正常发育率较高(96.30%vs.82.05%P=0.01),适应性较低(74.07%vs.92.31%P=0.02)。多因素回归分析显示,妊娠期LdT暴露与婴儿36个月时粗大运动发育(OR6.49,95%CI1.37-30.20,P=0.02)和适应性发育(OR0.18,95%CI0.05-0.71,P=0.01)独立相关。这些结果表明,长期观察产前LdT暴露可能会影响神经系统发育。缩写:LdT:替比夫定;HBV:乙型肝炎病毒;HBsAg:乙型肝炎表面抗原;HBeAg:肝炎Be抗原;HbsAb:乙型肝炎表面抗体;ALT:丙氨酸氨基转移酶;NA:核苷/核苷酸类似物;LAM:拉米夫定;MTCT:BMI母婴传播;GDS:Gesell发展指数;发育免疫球蛋白指数;OR:人民币指数:人民币指数;
    We prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in the third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Mothers with high HBV load were assigned to either the LdT group (n = 81, 600 mg of LdT each day from gestational week 28 to delivery) or the Control group (n = 39, untreated). Their infants were followed for 36 months to assess physical and neurological developments with Gesell Developmental Schedule tools. At 12 months after birth, the mean scores in the LdT group for gross motor, fine motor, adaptive, linguistic, and personal social domains were similar to those in the Control group. At 36 months, infants in the LdT group had higher mean scores for gross motor than the Control group (98.42 ± 9.69 vs. 94.54 ± 7.48, P = 0.03). In the LdT group, the rates of normal development were higher for gross motor (96.30% vs. 82.05% P = 0.01) and lower for adaptive (74.07% vs. 92.31% P = 0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant\'s development in gross motor (OR 6.49, 95% CI 1.37-30.20, P = 0.02) and adaptive (OR 0.18, 95% CI 0.05-0.71, P = 0.01) at 36 months. These results suggest that prenatal LdT exposure might affect neurological development in long-term observation.Abbreviations: LdT: telbivudine; HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis Be antigen; HbsAb: hepatitis B surface antibody; ALT: alanine aminotransferase; NA: nucleoside/nucleotide analog; LAM: lamivudine; MTCT: mother-to-child transmission; GDS: Gesell Developmental Schedule; OR: odds ratio; CI: confidence interval; DQ: developmental quotient; RMB: renminbi; BMI: body mass Index; HBIG: hepatitis B immunoglobulin.
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  • 文章类型: Journal Article
    This study aimed to investigate the effects of prenatal and lactational methcathinone exposure on the development and the learning and memory abilities of rat offspring using a Sprague-Dawley rat model. Pregnant and lactating rats were administered a consecutive daily dose of methcathinone (0.37 mg/kg) or an equivalent volume of saline by injection on gestational days 7-20 and postnatal days 2-15, respectively. The physical development and neurobehavioral test results of rat pups were recorded throughout the lactation period. Morris water maze (MWM) and novel object recognition (NOR) tests were performed from postnatal day 35 to day 42 to assess the learning and memory abilities of rat offspring in adolescence. The occurrence of hair growth and developments in neurological reflexes, such as improvements in limb grasp, righting reflex, and gait, were delayed in pups after perinatal methcathinone exposure compared with that in the control. Results from MWM and NOR tests indicate that perinatal methcathinone exposure induced deficits in spatial memory, learning ability, and novel object exploration in the adolescent offspring compared with that in the control. The impairment of spatial learning and memory was greater in the prenatal exposure group, while the impairment of novel object exploration was greater in the lactational exposure group. These data show that the prenatal and lactational methcathinone exposure induced the delay of physical and neurological reflex development and impaired learning and memory in rat offspring.
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  • 文章类型: Journal Article
    目的:为了评估疗效,左乙拉西坦(LEV)治疗癫痫的安全性和经济性。
    方法:PubMed,Scopus,Cochrane图书馆,OpenGrey.欧盟和ClinicalTrials.gov被搜索进行系统评价(SRs),荟萃分析,随机对照试验(RCT),观察性研究,2007年1月至2018年4月发布的病例报告和经济研究。我们使用气泡图以图形方式显示纳入研究的信息,并进行荟萃分析以定量综合证据。
    结果:共获得14,803条记录。我们纳入了30份SR/荟萃分析,34项随机对照试验,18项观察性研究,筛选过程后的58例病例报告和2项经济学研究。纳入的SRs招募了小儿癫痫患者,妊娠期癫痫,局灶性癫痫,全身性癫痫和难治性局灶性癫痫。对纳入的随机对照试验的荟萃分析表明,LEV与卡马西平一样有效(CBZ;治疗6个月:58.9%vs64.8%,OR=0.76,95%CI:0.50-1.16;12个月:54.9%vs55.5%,OR=1.24,95%CI:0.79-1.93),奥卡西平(57.7%vs59.8%,OR=1.34,95%CI:0.34-5.23),苯巴比妥(50.0%vs50.9%,OR=1.20,95%CI:0.51-2.82)和拉莫三嗪(LTG;61.5%vs57.7%,OR=1.22,95%CI:0.90-1.66)。SRs和观察性研究表明,孕妇的畸形率和宫内死亡率较低,以及认知副作用的低风险。但是不能排除精神和行为副作用。与CBZ相比,LEV降低了因不良事件导致的停药(OR=0.52,95%CI:0.41-0.65),而LEV与安慰剂和LTG比较时没有发现差异。使用决策树模型对难治性癫痫进行的两次成本效益评估显示,加拿大每无癫痫发作日获得76.18美元,韩国每无癫痫发作日获得44美元。
    结论:LEV与CBZ一样有效,奥卡西平,苯巴比妥和LTG对孕妇和认知功能具有优势。有限的证据支持其成本效益。
    PROSPERO(编号CRD42017069367)。
    OBJECTIVE: To evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.
    METHODS: PubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence.
    RESULTS: A total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50-1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79-1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34-5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51-2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90-1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41-0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea.
    CONCLUSIONS: LEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness.
    UNASSIGNED: PROSPERO (No CRD 42017069367).
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  • 文章类型: Journal Article
    OBJECTIVE: No consensus has been reached regarding whether brain injury related to congenital heart disease (CHD) is caused by infant cardiac surgery and/or prenatal injury resulting from the CHD. We performed this meta-analysis to identify the likely cause of neurodevelopmental delay in CHD patients.
    METHODS: We carried out a literature search without language restriction in December 2013, retrieving records from PubMed, EMBASE, the Cochrane Library and the World Health Organization trials center, to identify studies applying functional magnetic resonance imaging (fMRI) evaluation of brain function before surgery and, in some cases, after surgery (both immediate term and short term postoperatively). The preoperative and postoperative fMRI results were extracted, and meta-analysis was performed using Revman 5.1.1 and STATA 11.0, according to the guidelines from the Cochrane review and MOOSE groups.
    RESULTS: The electronic search yielded 937 citations. Full text was retrieved for 15 articles and eight articles (nine studies) were eligible for inclusion: six studies (n = 312 cases) with fMRI analysis before surgery and three (n = 36 cases) with complete perioperative fMRI analysis. The overall average diffusivity of CHD cases was significantly higher than that of controls, with a summarized standard (std) mean difference of 1.39 (95% CI, 0.70-2.08), and the fractional anisotropy was lower in CHD cases, with a summarized mean difference of -1.43 (95% CI, -1.95 to -0.91). N-acetylaspartate (NAA)/choline (Cho) for the whole brain was significantly lower in CHD cases compared with healthy ones, while lactate/Cho was significantly higher in CHD cases. Immediate term postoperatively, significant changes in NAA/creatine and NAA/Cho, relative to preoperative values, were found. However, the difference did not persist at the short-term follow-up.
    CONCLUSIONS: This meta-analysis suggests that the delay in neurological development in newborns with CHD is due mainly to prenatal injury, and cardiac surgery might lead to mild brain injuries postoperatively, but fMRI shows recovery within a short period.
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