局灶性癫痫患儿治疗前后肠道菌群的变化及意义北大核心CSCD

目的研究局灶性癫痫患儿与健康儿童肠道菌群是否不同,以及癫痫患儿治疗前后肠道菌群的变化。方法招募未经治疗的初诊局灶性癫痫患儿10例为病例组,且均用单药奥卡西平治疗。收集患儿临床资料,以及治疗前和治疗3个月后的粪便标本;另招募相同年龄段的健康儿童14例为对照组。提取粪便标本中细菌总DNA,进行16S rDNA测序,并行生物信息学分析。结果病例组经奥卡西平治疗3个月后癫痫发作频率减少>50%。门水平方面,治疗前组放线菌门丰度高于治疗后组和对照组(P<0.05);属水平方面,治疗前组埃希菌/志贺菌属、链球菌属、柯林斯菌属和巨单胞菌属丰度高于对照组(P<0.05),经治疗后其丰度降低(P<0.05)。结论与健康儿童相比,局灶性癫痫患儿的肠道菌群存在显著差异;奥卡西平可以显著改善癫痫症状,重塑癫痫患儿的肠道菌群。     

Recapitulation of fast skeletal muscle development in zebrafish by transgenic expression of GFP under the mylz2 promoter.

A 1,934-bp muscle-specific promoter from the zebrafish mylz2 gene was isolated and characterized by transgenic analysis. By using a series of 5' promoter deletions linked to the green fluorescent protein (gfp) reporter gene, transient transgenic analysis indicated that the strength of promoter activity appeared to correlate to the number of muscle cis-elements in the promoter and that a minimal -77-bp region was sufficient for a relatively strong promoter activity in muscle cells. Stable transgenic lines were obtained from several mylz2-gfp constructs. GFP expression in the 1,934-bp promoter transgenic lines mimicked well the expression pattern of endogenous mylz2 mRNA in both somitic muscle and nonsomitic muscles, including fin, eye, jaw, and gill muscles. An identical pattern of GFP expression, although at a much lower level, was observed from a transgenic line with a shorter 871-bp promoter. Our observation indicates that there is no distinct cis-element for activation of mylz2 in different skeletal muscles. Furthermore, RNA encoding a dominant negative form of cAMP-dependent protein kinase A was injected into mylz2-gfp transgenic embryos and GFP expression was significantly reduced due to an expanded slow muscle development at the expense of GFP-expressing fast muscle. The mylz2-gfp transgene was also transferred into two zebrafish mutants, spadetail and chordino, and several novel phenotypes in muscle development in these mutants were discovered.     

右美托咪定对七氟醚吸入麻醉诱导行颅脑手术围术期脑保护作用的影响：随机对照试验

文题释义：右美托咪定：是高选择性α2-肾上腺素受体激动剂,通过作用于中枢神经系统和外周神经系统的α2受体产生相应的药理作用。右美托咪定还有抗焦虑、降低应激反应、稳定血流动力学、镇痛、抑制唾液腺分泌、抗寒战和利尿等作用。此外,右美托咪定与其他镇静镇痛药物联合使用时具有良好的协同效应,能显著减少其他镇静镇痛药物的使用量。七氟醚：诱导迅速,刺激性小,血流动力学稳定,是临床广泛应用的吸入麻醉药之一。背景：颅脑手术中常使用的吸入麻醉剂是七氟醚,其具有起效速度快、循环稳定性好,且安全性高、不良反应少等优势,但是其还存在血压和心率异常以及躁动、疼痛等不良反应,因而需要一种辅助麻醉剂帮助改善不良反应。右美托咪定作为一种高效高选择性α2-肾上腺素受体激动剂,具有抗焦虑、催眠、镇痛、镇静及解交感作用,既往研究显示其可减轻七氟醚麻醉诱导后患者的躁动程度,减少围术期患者血流动力学波动,但尚缺乏在颅脑手术中进行验证。 目的：观察右美托咪定对七氟醚吸入麻醉诱导行颅脑手术患者的效果。方法：此次前瞻性、单中心、随机对照试验将在中国十堰市太和医院进行,拟纳入1 308例患者,以随机数字表法分为观察组和对照组,各654例。2组均以七氟醚行麻醉诱导下进行颅脑手术。观察组麻醉诱导前15 min予负荷剂量右美托咪定1 μg/kg静脉泵注10 min,继之以0.3 μg/(kg•h)持续泵注,手术前0.5 h停药;对照组以相同方式、同等速率输注同等剂量0.9%氯化钠注射液。试验于2015-12-08经十堰市太和医院伦理审查委员会批准(批准号2015GJJ-087)。参与者对试验方案和过程均知情同意,并签署知情同意书。试验已于2020-03-02在中国临床试验注册中心进行注册(注册号：ChiCTR2000030459),注册方案版本号1.0。结果与结论：①试验的主要观察指标为患者苏醒时间;②试验的次要观察指标为麻醉与恢复情况以及给予负荷剂量右美托咪定前、给予负荷剂量右美托咪定后、麻醉诱导期、开颅时、颅内操作期、关颅时、苏醒时的生命体征、应激指标、脑氧代谢指标以及不良事件;③2016年3月至2017年2月进行了190例的小样本前期试验,患者随机分为对照组和观察组,各95例,分别接受七氟醚麻醉诱导以及右美托咪定辅助麻醉+七氟醚麻醉诱导,结果显示2组麻醉时间、术中出血量、术中输液量、苏醒时间、拔管时间接近(P > 0.05),但与对照组相比,观察组血管活性药物麻黄碱以及艾司洛尔的用量较低(P < 0.05),给予负荷剂量右美托咪定后、麻醉诱导期、开颅时、颅内操作期、关颅时以及苏醒时心率与脑电双频指数较高(P < 0.05),开颅时、颅内操作期、关颅时与苏醒时平均动脉压较高(P < 0.05),给予负荷剂量右美托咪定后、麻醉诱导期、开颅时、颅内操作期、关颅时以及苏醒时血糖水平较高(P < 0.05),给予负荷剂量右美托咪定后、麻醉诱导期与开颅时皮质醇浓度较低(P < 0.05),颅内操作期、关颅时以及苏醒时静脉球部血氧饱和度、动脉-静脉球部血氧含量差以及脑氧摄取率较高(P < 0.05)。试验旨在验证右美托咪定可减少七氟醚吸入麻醉诱导颅脑患者血流动力学波动,降低应激指标,以及肯定的脑保护作用,这将为右美托咪定联合七氟醚吸入麻醉诱导应用于颅脑手术提供有力支持。ORCID: 0000-0002-2524-9449(刘勇攀) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios.

The glutamate pathways are involved in diverse processes such as learning and memory, epilepsy, and they play important roles in neural plasticity, neural development, and neurodegeneration. It has been proposed that autism could be a hypoglutamatergic disorder. Recently, Jamain et al. reported that the glutamate receptor 6 (GluR6 or GRIK2) is in linkage disequilibrium with autism. In the present study, the transmission disequilibrium test (TDT) and the haplotype transmission were performed to analyze the four SNPs (SNP1: rs995640; SNP2: rs2227281; SNP3: rs2227283; SNP4: rs2235076) of GluR6 in 174 Chinese Han parent-offspring trios. The TDT demonstrated that the two SNPs (SNP2 and SNP3) showed preferential transmission (TDT P = 0.032). The global chi(2) test for haplotype transmission also revealed an association between GluR6 and autism (chi(2) = 10.78, df = 3, P = 0.013). Our results suggested that GluR6 is in linkage disequilibrium with autism.     

Cysteinyl leukotriene receptor antagonist regulates vascular permeability by reducing vascular endothelial growth factor expression

BACKGROUND: Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Cysteinyl leukotrienes (cysLTs) potently elicit increased vascular permeability in airways, leading to airway edema. Vascular endothelial growth factor (VEGF) is 1 of the most potent proangiogenic cytokines and also increases vascular permeability so that plasma proteins can leak into the extravascular space. However, the mechanisms by which cysLTs induce increased vascular permeability are not clearly understood. OBJECTIVE: An aim of the current study was to determine the role of the cysLTs, more specifically in the increase of vascular permeability. METHODS: We used a BALB/c mouse model of allergic asthma to examine effects of cysLT receptor antagonists on bronchial inflammation and airway hyperresponsiveness, more specifically on the increase of vascular permeability. RESULTS: These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased vascular permeability, and increased levels of VEGF. Administration of cysLT receptor antagonists markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. CONCLUSION: These results indicate that cysLT receptor antagonists modulate vascular permeability by reducing VEGF expression and suggest that cysLT receptor may regulate the VEGF expression.     

两种塑化材料对断层解剖标本制作效果的比较

目的:研究2种不同塑化材料制作的断层解剖标本的差异.方法:分别采用硅橡胶技术和聚酯共聚体技术制备人体断层标本,并进行比较.结果:硅橡胶技术所制备的标本不透明;聚酯共聚体技术制备的断层解剖标本半透明.硅橡胶材料制备的断层标本不适于研究组织纤维走向和筋膜结构,适用于标本防腐保存;聚酯共聚体材料制备的断层标本可以清晰地显示组织的纤维走向和筋膜结构,同时标本的厚度均匀,表面平滑,硬度较高.结论:聚酯共聚体材料制备的断层标本优于硅橡胶材料,此方法将会发展成为断层解剖学研究的常用技术.     

Estimating gene penetrance from family data

Family data are useful for estimating disease risk in carriers of specific genotypes of a given gene (penetrance). Penetrance is frequently estimated assuming that relatives' phenotypes are independent, given their genotypes for the gene of interest. This assumption is unrealistic when multiple shared risk factors contribute to disease risk. In this setting, the phenotypes of relatives are correlated even after adjustment for the genotypes of any one gene (residual correlation). Many methods have been proposed to address this problem, but their performance has not been evaluated systematically. In simulations we generated genotypes for a rare (frequency 0.35%) allele of moderate penetrance, and a common (frequency 15%) allele of low penetrance, and then generated correlated disease survival times using the Clayton‐Oakes copula model. We ascertained families using both population and clinic designs. We then compared the estimates of several methods to the optimal ones obtained from the model used to generate the data. We found that penetrance estimates for common low‐risk genotypes were more robust to model misspecification than those for rare, moderate‐risk genotypes. For the latter, penetrance estimates obtained ignoring residual disease correlation had large biases. Also biased were estimates based only on families that segregate the risk allele. In contrast, a method for accommodating phenotype correlation by assuming the presence of genetic heterogeneity performed nearly optimally, even when the survival data were coded as binary outcomes. We conclude that penetrance estimates that accommodate residual phenotype correlation (even only approximately) outperform those that ignore it, and that coding censored survival outcomes as binary does not substantially increase the mean‐square errror of the estimates, provided the censoring is not extensive. Genet. Epidemiol. 34: 373–381, 2010. © 2010 Wiley‐Liss, Inc.     

广州地区患儿感染幽门螺杆菌vacA、cagA及iceA基因研究

目的探讨广州地区患儿感染幽门螺杆菌（Hp）的vacA、cagA、iceA的基因亚型和优势基因亚型。方法105例胃、十二指肠疾病患儿的胃窦处取3块胃黏膜,分别进行快速尿素酶反应、病理检查和聚合酶链反应（PCR）。抽提胃黏膜基因组DNA,用11对引物,检测HpureA、vacA、cagA和ieeA基因,分析HpvacA、cagA、iceA基因亚型。结果快速尿素酶反应、病理检查和PCR三者均阳性的标本52例,其中感染Hp vacA s1as1c／m2、s1as1c／m1T亚型菌株的阳性率分别是82．7％（43／52）、9．6％（5／52）,m区不能分型占7．7％（4／52）,Hp vacA s1as1c／m2与其他基因亚型相比较,差异有统计学意义。Hp vacA s1a和s1c亚型总是同时检出,未发现Hp vacA s1b、s2、m1亚型。HpcagA^＋菌株检出率是90．4％（47／52）,cagA^-菌株检出率9、6％（5／52）,二者比较,差异有统计学意义。Hp iceA1亚型菌株单独检出率78．8％（41／52）,Hp iceA2亚型菌株单独检出率是1．9％（1／52）,Hpi ceA1和ieeA2亚型均阳性是3．8％（2／52）,iceA1和iceA2亚型均阴性的比率是15．4％（8／52）,Hp iceA1亚型阳性率与其他基因亚型相比较,差异有统计学意义。结论Hp的Hp vacA s1as1c／m^2、cagA^＋、iceA1亚型是广州地区患儿感染的Hp的优势基因亚型,Hp vacA s1as1c／m^2、cagA。和iceA1基因组合是广州地区患儿感染的Hp的优势基因亚型组合。     

七年制医学生消化内科临床见习带教体会

七年制医学生基础知识扎实、自学能力强,但临床分析和解决问题的实际工作能力欠缺,而临床见习是医学生理论联系实际的纽带和桥梁。因此,努力提高临床见习的带教效果,对于医学生理解、巩固所学基础知识,为临床实习奠定良好的实践基础至关重要。现结合我科多年带教七年制学生见习的具体情况,探讨如何提高七年制医学生临床见习的带教效果。1传统消化内科见习带教中的困难和缺陷消化内科理论课学时多、专业性强,学习内容多、概念抽象,使学生理解较困难。过去见习带教中大部分时间以教师讲课为主,学生多处于被动地位,部分学生出现厌烦、兴趣不浓…