用于外周神经的干涉电流刺激器设计

设计了一种用于外周神经电刺激的干涉电流刺激器。该刺激器为两路电流输出,可以产生4种波形,每种波形的频率、幅度等参数可在上位机进行设置,频率分辨率为0.2 Hz,幅度分辨率为0.01 mA,时间分辨率为0.1 μs。该刺激器的特点在于可在刺激强度一定的条件下连续改变电流比,或在电流比一定的情况下连续改变刺激强度。上位机采用LabVIEW开发,下位机采用FPGA对3片DAC进行控制,DAC产生的波形信号经过隔离恒流源电路后施加到负载。经过测试,刺激器能够准确产生4种波形,电流偏差在2.6%以内,恒流效果良好。该刺激器体积小,操作简单,产生波形稳定,可以用于无损选择电刺激研究。     

重症哮喘靶向治疗的研究进展

支气管哮喘(简称哮喘)是一种慢性气道炎症性疾病,具有明显的异质性和复杂的病理生理表现.我国成人的哮喘患病率为1.24%,其中重症哮喘占5.99%.重症哮喘表现为控制水平差,是哮喘致残、致死的主要原因,临床治疗棘手.近年来,针对辅助T细胞(helper T cell,Th)2和Th17表型的生物靶向治疗药物成为哮喘新药开发的热点之一.生物靶向治疗药物为重症哮喘患者带来了新的希望.现就重症哮喘靶向治疗的研究现状进行综述,以期为临床医师治疗重症哮喘提供参考.     

Trio‐whole‐exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations

Whole‐exome sequencing (WES) is widely used to detect genetic mutations that cause Mendelian diseases, and has been successfully applied in combination with preimplantation genetic diagnosis (PGD) to avoid the transmission of genetic defects. We investigated 40 nonconsanguineous families with unexplained, recurrent fetal malformations (two or more malformed fetuses) from May 2016 to December 2018. Using Trio‐WES, we identified 32 disease‐associated variants in 40 families (80% positive rate), which were subsequently verified. Known Mendelian diseases were identified in 12 families (30%), highly suspected Mendelian diseases in 12 families (30%), variants with uncertain significance in 8 families (20%), and no noticeable variants for 8 families (20%). Further analysis showed variants in 22 genes may cause fetal malformations. Four gene variants were detected in fetuses for the first time, which expanded the spectrum of the disease phenotype. Two novel candidate genes may be related to fetal malformations. Of 26 couples receiving PGD on disease‐associated genes, 3 healthy newborns were delivered, and 4 couples are undergoing pregnancies. We reported the fetal data and developed an optimized genetic testing strategy. Our finding strongly suggests the presence of single gene Mendelian disorders in 60% of those families, and PGD services for couples to have healthy babies.     

LEAP: Using machine learning to support variant classification in a clinical setting

Advances in genome sequencing have led to a tremendous increase in the discovery of novel missense variants, but evidence for determining clinical significance can be limited or conflicting. Here, we present Learning from Evidence to Assess Pathogenicity (LEAP), a machine learning model that utilizes a variety of feature categories to classify variants, and achieves high performance in multiple genes and different health conditions. Feature categories include functional predictions, splice predictions, population frequencies, conservation scores, protein domain data, and clinical observation data such as personal and family history and covariant information. L2‐regularized logistic regression and random forest classification models were trained on missense variants detected and classified during the course of routine clinical testing at Color Genomics (14,226 variants from 24 cancer‐related genes and 5,398 variants from 30 cardiovascular‐related genes). Using 10‐fold cross‐validated predictions, the logistic regression model achieved an area under the receiver operating characteristic curve (AUROC) of 97.8% (cancer) and 98.8% (cardiovascular), while the random forest model achieved 98.3% (cancer) and 98.6% (cardiovascular). We demonstrate generalizability to different genes by validating predictions on genes withheld from training (96.8% AUROC). High accuracy and broad applicability make LEAP effective in the clinical setting as a high‐throughput quality control layer.     

Cumulative live birth rates of in vitro fertilization/intracytoplasmic sperm injection after multiple complete cycles in China

There were few studies of cumulative live birth rates (CLBRs) based on multicenter reproductive clinical data from the general Chinese population. Here we report a retrospective cohort study, including 14 311 women with 17 315 cycles, in three reproductive centers to evaluate two estimated parameters of CLBRs with multiple transfer cycles of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a Chinese population. We found that CLBRs were related to female age and endometrial thickness. By the fourth transfer cycle, the conservative and optimal estimates of CLBRs were 52.95% and 77.30% in women under 30 years of age, and 18.17% and 26.51% in those 37 years of age or older, respectively. The two estimates were 44.70% and 63.15% in women with endometrial thickness more than 7 mm, and 32.05% and 46.18% in those with less than 7 mm, respectively. In addition, body mass index (BMI), duration of infertility, and infertility diagnoses may also be related to CLBRs on certain conditions. The findings from this study on CLBRs after multiple transfer cycles of IVF/ICSI treatment on different conditions in the Chinese population should be beneficial to both infertile couples and clinicians.     

芹菜素治疗去卵巢骨质疏松模型大鼠的作用与剂量

文题释义： 芹菜素：主要存在于瑞香科、马鞭草科、卷柏科植物中,如芫花,卷柏中含量较大。芹菜素属于黄酮类,具有抑制致癌物质的致癌活性;作为治疗HIV和其他病毒感染的抗病毒药物;MAP激酶的抑制剂;治疗各种炎症;抗氧化剂;镇静、安神;降压。与其他黄酮类物质(槲皮素、山奈黄酮)相比具有低毒、无诱变性等特点。 骨密度：全称是骨骼矿物质密度,是骨骼强度的一个重要指标,以g/cm³表示,是一个绝对值。在临床使用骨密度值时由于不同的骨密度检测仪的绝对值不同,通常使用T值判断骨密度是否正常。T值是一个相对值,正常参考值在-1和+1之间。当T值低于-2.5时为不正常。骨密度,是骨质量的一个重要标志,反映骨质疏松程度,预测骨折危险性的重要依据。 背景：研究证实芹菜素具有抗病毒、抗炎、抗氧化、镇静安神等功效。 目的：研究不同剂量芹菜素对大鼠骨质疏松的疗效并探讨其机制。 方法：实验方案经南方医科大学动物实验伦理委员会批准。成年雌性SD大鼠42只,通过卵巢切除法建立大鼠骨质疏松模型,实验分为7组,每组6只大鼠,分别为假手术组、芹菜素20,40,60和80 mg/kg组、对照组、阳性对照组。假手术组未摘除卵巢,阳性对照组每天灌胃烯雌酚(0.02 mg/kg)、维生素D和钙;对照组给予同等量纯净水皮下注射;芹菜素各组分别给予相应剂量的芹菜素皮下注射;1次/d,用药8周。分别检测干预后第4周和第8周大鼠股骨密度和血清中钙、磷、骨碱性磷酸酶、Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽的水平。 结果与结论：①与对照组比较,芹菜素剂量为40,60和80 mg/kg时,大鼠的骨密度、血清中钙、磷在第4周和第8周时均较高(P < 0.05),Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽、骨碱性磷酸酶较低(P < 0.05);②与阳性对照组比,芹菜素剂量为60 mg/kg和80 mg/kg时,大鼠的骨密度、血清中钙、磷和骨碱性磷酸酶、Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽在第4周和第8周时均无明显差别(P > 0.05),剂量为 20 mg/kg和 40 mg/kg时,骨密度、血清中钙、磷、均比阳性对照组低(P < 0.05),Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽比阳性对照组高(P < 0.05);③对照组和假手术组比较,在第4周和第8周时大鼠骨密度、 血清中钙、磷均比较低(P < 0.05),Ⅰ型前胶原氨基末端前肽、β-Ⅰ型胶原C-末端肽均比较高(P < 0.05);④结果说明,去卵巢法建立大鼠骨质疏松模型确实有效;芹菜素对骨质疏松的治疗作用和剂量相关,一定剂量的芹菜素具有类似烯雌酚样的抗骨质疏松效果。 ORCID: 0000-0002-9167-5286(赖丽金) 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     

青少年特发性脊柱侧凸腰主弯患者腰椎-骨盆的生物力学分析

文题释义： 青少年特发性脊柱侧凸：为脊柱三维平面上的畸形,会导致青少年脊柱结构发生明显的改变,结构的改变会导致椎骨及椎间盘应力发生相应的改变,且腰椎、骨盆在人体中的力学作用极为重要,青少年时期为人体脊柱生长发育的高峰期,脊柱结构及应力的改变在该时期的进展尤为明显。 背景：青少年特发性脊柱侧凸导致脊柱结构和应力发生改变,腰椎在脊柱中承受的载荷最大,骨盆也起着传导重力的作用,故青少年特发性脊柱侧凸腰主弯患者腰椎骨盆的生物力学分析尤为重要。 目的：建立青少年特发性脊柱侧凸腰主弯腰椎-骨盆三维数字化模型并进行有限元分析。 方法：根据1例13岁女性特发性脊柱侧凸腰主弯患者的腰椎-骨盆CT薄层数据,应用Mimics 15.0软件重建三维数字化模型,以Pro/E 5.0软件建立初步几何模型并导入Hypermesh 13.0进行网格划分,最终通过Abaqus 6.14软件对该模型进行有限元分析。分析有限元模型在6种载荷条件下的位移、应力变化及该模型各椎体及椎间盘的应力变化。患者家属对试验方案知情同意,且得到医院伦理委员会批准。 结果与结论：①建立了青少年特发性脊柱侧凸腰主弯患者的腰椎-骨盆的三维有限元模型;②模型在6种载荷条件下,L₁椎体上部在左、右侧屈时位移变化最大,骶骨下端在前屈时位移最大;③椎间盘右缘在右侧屈运动条件下所受应力最大;前屈位时,腰椎间盘所受应力为前缘最大,左缘所受应力最小;后伸位时后缘所受应力最大,而右缘所受应力最小;侧屈位及旋转位时,右缘所受应力最大,前缘所受应力最小;④L₅在6种运动中应力均最大,其中应力集中于上下关节突及椎弓根,尤其以右侧最为集中;⑤提示青少年特发性脊柱侧凸不同载荷会引起椎体或椎间盘不同位置受力及位移有相应变化,研究结果对脊柱侧凸的治疗和预防具有重要意义。 ORCID: 0000-0001-5810-6674(张聪) 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     

外泌体在骨不连治疗中的作用机制及进展

文题释义：外泌体：是细胞外囊泡小体,由不同类型的细胞释放,根据其自身各种特性,可运用于损伤组织间药物的传递,作为生物标志物,介导细胞间信息交流等巨大作用。 哺乳动物雷帕霉素靶蛋白信号通路：哺乳动物雷帕霉素靶蛋白(mTOR)是一种蛋白激酶,其催化亚单位是2种生化上截然不同的复合物mTORC1和mTORC2,对骨形成的调节非常重要。背景：骨不连是骨折术后常见的并发症,给患者带来了极大的困扰。随着外泌体技术的不断研发,外泌体在骨不连的治疗中逐渐显露优势,成为医疗工作新的研究方向。 目的：从国内外研究中归纳总结,探讨外泌体在骨不连治疗中的作用。 方法：中文以“外泌体,骨不连,骨重塑,骨再生,血管损伤,成骨细胞,破骨细胞”检索万方、中国知网、维普文献数据2003至2019年的相关文献,英文以“exosomes,nonunion,bone remodelling”,检索PubMed数据库2003至2019年的相关文献,根据纳入及排除标准摘选50篇文章。结果与结论：①近年来,外泌体作用于骨不连的研究得到越来越多的重视,外泌体中的miRNA及蛋白质可以通过影响骨细胞的分化作用于骨不连;②随着进一步的研究发现,外泌体可通过调节骨重塑,促进血管修复,改善系统性疾病等方面治疗骨不连;③但是目前对于外泌体的研究仍处于实验阶段,如何将其更好地应用于临床治疗还需进一步的探究。ORCID: 0000-0003-0172-7642(赖渝) 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     

Asymptomatic long-segmental type A aortic dissection diagnosed by transthoracic echocardiography: A case report and literature review

Aortic dissection (AD) is a life-threatening disease. Patients usually experience severe pain in the chest, back, or abdomen, but some patients report a variety of other symptoms without pain. Completely asymptomatic AD is sporadic and probably under-recognized. The present study aimed to (a) report an extremely rare case of asymptomatic long-segmental type A AD, wherein exaggeratedly low diastolic blood pressure and broad pulse pressure were the primary signs, and (b) summarize the clinical characteristics of asymptomatic AD through the literature review.