10p末端三体致多发畸形的临床表型及遗传学分析

目的分析1例多发畸形患儿的遗传学原因,探讨其染色体变异与表型的相关性。方法应用常规G显带分析患儿外周血染色体核型,采用低覆盖度全基因组高通量测序技术(low-coverage massively parallel copy number variation sequencing,CNV-seq)进行DNA拷贝数变异分析,并通过荧光原位杂交对患儿及父母进行验证,以判断变异区域的结构变化和遗传学来源。结果G带检测患儿核型为46,XX,3pter+?。CNV-seq分析结果显示患儿10pl3pl5.3区存在约13.5 Mb重复(60466〜13556655)和3p26.3区存在636 kb微缺失(60064〜695821)0对患儿及父母进行FISH验证,明确患儿核型为46,XX,ish der(3)t(3;10)(10p+,3p dim),父母荧光原位杂交验证结果未见异常,提示患儿为新发变异。结论患儿的10pl3pl5.3重复与智力缺陷、生长迟缓、畸形表型、胃食管返流等临床表型相关。3p末端缺失涉及CHL1基因,该基因在大脑的构建和功能中起重要作用,可能同时协作影响患儿的智力发育。     

基于ClinicalTrials.gov注册平台分析的组织工程临床试验注册的现状

文题释义：ClinicalTrials.gov注册平台：ClinicalTrials.gov注册平台现由美国国立卫生研究院(National Institutes of Health,NIH)国家医学图书馆(National Library of Medicine,NLM)维护,是国际上使用最普遍的临床试验注册平台,涵盖了美国50个州和另外208个国家/地区开展的多个领域的近30万项临床试验;此外,在该平台进行临床试验注册符合国际医学期刊编辑委员会(International Committee of Medical Journal Editors,ICMJE)对相关论文发表的要求。 对组织工程临床转化研究的意义：基于ClinicalTrials.gov注册平台中的临床试验注册数据,通过对组织工程领域临床试验的注册数量、适应证、申办者、分期等角度进行统计分析,全面把握该领域的临床试验注册现状,以期为组织工程临床转化研究提供参考和证据支持。 背景：组织器官市场供求不平衡,积极开展组织工程基础研究并加快临床转化至关重要。 目的：对组织工程临床试验注册现状进行整体分析,为组织工程临床转化研究提供参考和证据支持。 方法：通过ClinicalTrials.gov注册平台采集数据,利用文献计量法和数理统计法,从注册数量、适应证、申办者、分期等角度对组织工程临床试验注册现状进行分析。 结果与结论：①全球组织工程领域临床试验434项,中国65项;全球和中国均是超过一半为随机对照试验,全球18项国际多中心临床试验中未见中国机构参与;全球和中国分别涵盖适应证57种、37种,主要集中于骨和软骨、牙、皮肤等领域;全球申办者275个,中国33个;②全球和中国均是Ⅰ期/Ⅱ期临床试验注册数量最多;③通过对组织工程临床试验注册现状的分析发现,组织工程领域的临床应用转化较少,中国虽然注册数量在全球占据第二位,但与美国仍存在一定差距;已经积累了一定数量的高证据级别的临床试验,但缺乏高潜在国际市场价值的产品;研究机构和医疗机构对临床转化研究更为重视,临床应用主要集中于骨和软骨、牙及皮肤的缺损或功能缺陷的治疗,主要处于安全性或有效性评价阶段。 ORCID: 0000-0002-7227-732X(卢岩) 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     

Endobutton袢钢板与Rigidfix横穿钉股骨端固定自体腘绳肌腱重建前交叉韧带的转归

文题释义： 前交叉韧带重建：前交叉韧带是控制膝关节前向稳定的一个重要结构,包括前内侧和后外侧束。前交叉韧带对膝关节稳定提供了强有力的支持,当它出现完全断裂,膝关节会出现明显不稳定的情况。目前最常用的治疗方案为采用关节镜取腘绳肌等肌腱来重建交叉韧带,恢复膝关节的稳定性。 Rigidfix横穿钉：DePuy Mitek RIGIDFIX BIOCRYL股骨3.3 mm ST交叉钉为一种可吸收多聚乳酸和磷酸三钙植入物,用于重建前交叉韧带时,将软组织(半腱肌和股薄肌)移植物固定于股骨。 背景：固定方式的选择是影响前交叉韧带重建预后的重要因素,Endobutton袢钢板和Rigidfix横穿钉作为目前应用较为广泛的2种股骨端悬挂固定装置,它们的优点是固定强度大,肌腱与骨隧道接触面积大,有利于腱-骨愈合等。但这2种固定方法本身在临床疗效、骨隧道扩大等方面是否存在差异还有争议。 目的：探讨Endobutton袢钢板与Rigidfix横穿钉股骨端固定自体腘绳肌腱重建前交叉韧带术后的转归。 方法：回顾性分析2015年6月至2017年12月开展前交叉韧带重建并进行了第2次关节镜探查的 270例病例。所有患者对治疗方案均知情同意,且得到医院伦理委员会批准。根据股骨端固定方式将患者分成 2 组,Endobutton组150例采用Endobutton袢钢板行自体腘绳肌腱股骨端固定重建前交叉韧带;Rigidfix组120例采用Rigidfix横穿钉行自体腘绳肌腱股骨端固定重建前交叉韧带,2组胫骨端均采用Bioabsorbable Interference Screw+AO空心钉固定。采用 MRI 测量2组骨隧道扩大情况,采用Lysholm评分、国际膝关节文献委员会评分、Tenger评分表及抽屉试验、Lachman试验、轴移试验、KT-1000关节测量仪评价膝评价膝关节功能恢复情况及稳定性;术后1年二次关节镜探查时观察移植物连续性、移植物滑膜覆盖情况以及关节内是否有异常结构。 结果与结论：①所有患者均获得随访,随访时间14-44个月;②术后1年Endobutton组股骨端和胫骨端骨隧道扩大均较Rigidfix组明显(P < 0.05);③术后1年2组患者术后 Lysholm评分、Tegner评分、国际膝关节文献委员会评分均较术前改善(P < 0.05),2组间术后评分差异无显著性意义(P > 0.05);④术后1年2组膝关节活动度对比差异无显著性意义(P > 0.05);⑤二次探查前2组患者前抽屉试验、Lachman试验、轴移试验情况对比差异无显著性意义(P > 0.05);Endobutton组KT-1000侧-侧差值为(1.12±1.20) mm,Rigidfix组KT-1000侧-侧差值为(1.23±0.91)mm,2组对比差异无显著性意义(P > 0.05);⑥二次关节镜探查示Endobutton组患者移植物完全吸收1例、移植物磨损11例;Rigidfix组患者移植物完全吸收2例,移植物磨损15例,2组差异无显著性意义(P > 0.05);⑦二次探查时移植物滑膜覆盖程度Endobutton组优59例,良61例,差30例;Rigidfix组优47例,良49例,差24例,2组差异无显著性意义(P > 0.05);⑧Endobutton组术后并发症的发生率为2.6%,Rigidfix组为6.6%,2组差异无显著性意义(P > 0.05);⑨结果表明,Endobutton袢钢板与Rigidfix横穿钉股骨端固定自体腘绳肌腱重建前交叉韧带效果相当,二次探查移植物滑膜覆盖及连续性无明显差异;但与Rigidfix横穿钉系统相比,股骨端采用 Endobutton固定更易引起骨隧道扩大。 ORCID: 0000-0002-4264-8492(赵立连) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

应用文献计量学及可视化技术分析富血小板血浆全球研究特征及趋势

文题释义：文献计量学：是指用数学和统计学的方法,定量地分析一切知识载体的交叉科学。它是集数学、统计学、文献学为一体,注重量化的综合性知识体系。其计量对象主要是：文献量(各种出版物,尤以期刊论文和引文居多)、作者数(个人集体或团体)、词汇数(各种文献标识,其中以叙词居多)文献计量学最本质的特征在于其输出务必是“量”。 可视化技术：完整的地理空间信息可视化概念主要包括科学计算可视化、数据可视化和信息可视化。地理空间信息可视化技术的核心是为使用者提供空间信息直观的、可交互的可视化环境。 背景：研究认为,富血小板血浆可以促进组织的修复和再生。 目的：通过文献计量学的方法评价全球富血小板血浆领域的研究现状和热点。 方法：在web of science核心库中,采用普通检索的方式,以“platelet rich plasma”等为关键词进行主题检索,分析从建库至2018-12-25发表的相关研究。通过对已检索的文献按照国家地区、机构、出版年、来源出版物名称等分别进行索引和分析。使用Excel 2007进行描述性统计。使用VOS viewer (Leiden University,荷兰)软件对检索的全部条目进行分析并绘制图形。主要评价指标包括：共现关系、互引关系、共引关系以及合作关系图。 结果与结论：①共检索到8 499篇富血小板血浆方面的研究,研究数量和被引用次数逐年增加;②富血小板血浆研究数量排名前3名的国家是美国、意大利和日本;③富血小板血浆的学科方向和研究领域主要涉及5方面：生长因子功能的基础研究、骨再生领域研究、软骨或骨关节炎相关领域的临床研究、血小板功能研究以及干细胞相关研究领域;④基于大数据的分析结果提示,富血小板血浆的主要研究和应用领域在骨科,尤其是软骨再生和骨关节炎方面,未来富血小板血浆的研究重心和科技投入应该向其倾斜。 ORCID: 0000-0001-6966-3134(邢丹) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

基于专利分析看肝脏组织工程领域的竞争态势

文题释义：肝脏组织工程：肝脏组织工程基于组织工程概念,应用生命科学与工程学的原理与技术,利用分离的肝细胞复合特定的支架材料,制造出完整的、可植入、且具有更全面功能、可用于临床肝移植的器官。 专利分析：对专利说明书、专利公报中大量零碎的专利信息进行分析、加工、组合, 并利用统计学方法和技巧使这些信息转化为具有总揽全局及预测功能的竞争情报, 从而为技术、产品及服务开发中的决策提供参考。背景：中国是肝病高发国家,肝脏组织工程为治疗带来了新的希望,但目前此技术仍处于探索阶段。 目的：对肝脏组织工程领域的专利进行分析,揭示全球技术竞争态势,为中国肝脏组织工程的发展与创新提供借鉴和参考。 方法：对近20年肝脏组织工程领域的专利数量与发展趋势、技术发源地、目标市场、申请机构、发明人和技术分布等进行分析,全文检索关键词包括组织工程(tissue engineering)、组织修复或组织再生 (tissue regenerate/repair)和肝(hepatic/liver)等。检索截止时间为2018年12月28日。结果与结论：①全球肝脏组织工程领域发展速度较快,近10年复合增长率8.64%,其中发明专利占84.93%。②中国是全球肝脏组织工程最主要的技术发源地。但三方专利数量远不及美国和日本。③中国和美国是肝脏组织工程领域的最受关注的两大目标市场,但申请人多集中于本国,国际授权数量较少。④在专利权人和发明人排名中,中国分别有8家机构和14位申请人跻身全球前20。⑤结果证实,从专利分析结果来看,中国肝脏组织工程技术发展迅猛,跻身国际前列,但缺乏核心技术,各研发主体还应不断提升创新能力,挖掘高价值技术,从而提高国际竞争力。 ORCID: 0000-0002-8864-5449(王婷婷) 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     

PEER umbrella systematic review of systematic reviews: Management of osteoarthritis in primary care

ObjectiveTo determine how many patients with chronic osteoarthritis pain respond to various non-surgical treatments.Data sourcesPubMed and the Cochrane Library.Study selection Published systematic reviews of randomized controlled trials (RCTs) that included meta-analysis of responder outcomes for at least 1 of the following interventions were included: acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, cannabinoids, counseling, exercise, platelet-rich plasma, viscosupplementation, glucosamine, chondroitin, intra-articular corticosteroids, rubefacients, or opioids.Synthesis In total, 235 systematic reviews were included. Owing to limited reporting of responder meta-analyses, a post hoc decision was made to evaluate individual RCTs with responder analysis within the included systematic reviews. New meta-analyses were performed where possible. A total of 155 RCTs were included. Interventions that led to more patients attaining meaningful pain relief compared with control included exercise (risk ratio [RR] of 2.36; 95% CI 1.79 to 3.12), intra-articular corticosteroids (RR = 1.74; 95% CI 1.15 to 2.62), SNRIs (RR = 1.53; 95% CI 1.25 to 1.87), oral NSAIDs (RR = 1.44; 95% CI 1.36 to 1.52), glucosamine (RR = 1.33; 95% CI 1.02 to 1.74), topical NSAIDs (RR = 1.27; 95% CI 1.16 to 1.38), chondroitin (RR = 1.26; 95% CI 1.13 to 1.41), viscosupplementation (RR = 1.22; 95% CI 1.12 to 1.33), and opioids (RR = 1.16; 95% CI 1.02 to 1.32). Preplanned subgroup analysis demonstrated no effect with glucosamine, chondroitin, or viscosupplementation in studies that were only publicly funded. When trials longer than 4 weeks were analyzed, the benefits of opioids were not statistically significant.ConclusionInterventions that provide meaningful relief for chronic osteoarthritis pain might include exercise, intra-articular corticosteroids, SNRIs, oral and topical NSAIDs, glucosamine, chondroitin, viscosupplementation, and opioids. However, funding of studies and length of treatment are important considerations in interpreting these data.     

Lifestyle intervention to prevent gestational diabetes mellitus and adverse maternal outcomes among pregnant women at high risk for gestational diabetes mellitus

ObjectiveWe assessed the effects of a lifestyle intervention on gestational diabetes mellitus (GDM) incidence and risk of adverse maternal outcomes among pregnant women at high risk for GDM.MethodsFrom July to December 2018, we enrolled 1822 eligible pregnant women; of these, 304 had at least one risk factor for GDM. Participants were randomly allocated to the intervention or control group. Usual prenatal care was offered to both groups; the intervention group also received individually modified education on diet, physical activity, and weight control. The GDM diagnosis was based on an oral glucose tolerance test at 24–28 gestational weeks. Multivariate logistic regression was used to evaluate the effects of the lifestyle intervention on risk of GDM and adverse maternal outcomes.ResultsA total of 281 women (139 in the intervention group and 142 controls) were included. Incidences of GDM and adverse maternal outcomes were all significantly lower in the intervention than in the control group. Multivariate logistic regression indicated that women in the intervention group had a lower risk of GDM and adverse maternal outcomes, after adjusting potential confounding factors.ConclusionThe present lifestyle intervention was associated with lower risks of GDM and adverse maternal outcomes.     

High-mobility group box 1 exacerbates CCl4-induced acute liver injury in mice

High-mobility group box 1 (HMGB1) is a nuclear factor that can also serve as an imflammatory mediator once released into extracellular milieu. Therefore, HMGB1 has been recognized to play a pivotal role in inflammatory diseases such as sepsis, acute lung injury, ischemia reperfusion injury and type 1 diabetes. Nevertheless, its impact on carbon tetrachloride (CCl₄)-induced hepatic injury is yet to be elucidated. In the present report, we demonstrated evidence indicating that high levels of HMGB1 were not only present in the necrotic area of liver but also in the serum after CCl₄ challenge. In line with these observations, administration of exogenous recombinant HMGB1 exacerbated CCl₄-induced hepatic injury, while HMGB1 blocking antibody provided protection for mice against CCl₄-induced acute liver injury as evidenced by the decrease of serum transaminase and reduction of hepatic tissues necrosis. Mechanistic studies revealed that blockade of HMGB1 attenuated CCl₄-induced MDA accumulation along with improved SOD and GSH activity. Treatment of mice with HMGB1 neutralizing antibody also significantly inhibited the production of proinflammatory mediators TNF-α and IL-6 along with attenuated HMGB1 expression and its extracellular release. Together, our data suggest an essential role for HMGB1 in CCl₄-induced acute liver injury, while HMGB1 neutralizing antibody could be served as an effective regimen for preventing CCl₄-induced acute liver injury.     

Analysis of Heart Rate Variability in Chinese PLA Navy Global Visiting Task Group

Objective： To analyze the heart rate variability in Chinese PLA navy global visiting task group. Methods：We analyzed the heart rate variability in Holter in 77 men and 4 women for 5-15 days before voyage, and 65-75 and 115-125 days after voyage, and 29 men and 3 women for 5-15 days after having finished voyage. Results：NN50 and VLF were lower in 77 men and 4 women for 65-75 days after voyage than that was 5-15 days before voyage （P＆lt;0.01）. SDANN was lower in 77 men and 4 women for 115-125 days after voyage than that was 65-75 days after voyage （P＆lt;0.01）. SDNN, SDANN, SDNN index, RMSSD, NN50, PNN50,Triangular index, VLF, HLF, VAI and VLI were lower in 77 men and 4 women for 65-75 days after voyage than that was 5-15 days before voyage （P＆lt;0.01）.Conclusion： These findings suggest that voyage may reduce heart rate variability for a long time.     

白纹伊蚊气味受体基因OR21α的克隆及定量分析

本文克隆白蚊伊蚊气味受体基因OR21a分析其是否与搜寻宿主或吸血行为相关。通过设计简并引物,PCR扩增得到白纹伊蚊气味受体基因OR21a段,采用SYBR荧光定量PCR方法,以自纹伊蚊β-肌动蛋白基因作为内参,比较了OR21a因在未吸血雌蚊、雄蚊、打断吸血雌蚊和饱血雌蚊头部表达量的差异。结果显示,白纹伊蚊OR21a因在未吸血雌蚊头部表达量最高,饱血雌蚊头部表达量最低,而在雄蚊头部的表达量介于打断吸血雌蚊和饱血雌蚊之间。本研究发现白蚊伊蚊会依据不同的生理需求改变OR21a因的表达量,推测可能与白纹伊蚊搜寻宿主及吸血行为有一定的相关性。