POLG 基因变异致线粒体病一家系分析

目的分析POLG基因变异致线粒体病的临床表型及基因变异。方法回顾分析于2019年5月就诊,并经采集外周血DNA进行医学外显子、外显子-内含子交界区靶向二代测序和一代验证,1个确诊为POLG基因变异致线粒体病家系的临床资料。结果先证者,男,10岁,与其同卵双胎哥哥均有相同的体征,深感觉受损、腱反射消失、肌肉可疑萎缩。先证者3个兄姐先后于1岁多夭折。提取患儿及其父母的外周血,先证者及同卵双胎哥哥POLG基因均存在G.2558A(p.R853Q)、c.2890T(p.R964C)复合杂合变异,分别来源于患儿父母亲。结论 POLG基因复合杂合变异线粒体病家系成员有不同的表型;POLG相关疾病,即使同种基因变异,其临床异质性也较大。     

漏斗胸Nuss矫形术对胸廓的影响及相关因素分析

目的通过CT影像测量了解漏斗胸Nuss矫形术前后胸廓径线的改变情况,探讨并分析Nuss矫形术对胸廓的影响及相关因素。方法对2014年1月至2018年12月郑州大学第一附属医院收治的50例行漏斗胸Nuss矫形术患儿的临床资料进行回顾性分析。50例患儿中男43例,女7例。所有患儿中存在脊柱侧弯6例,胸廓不对称12例,胸骨旋转11例。通过CT影像测量其放置矫形器前及取出矫形器后胸廓各椎体平面最大横内径及该平面胸脊间的距离,通过配对样本t检验比较矫形前后各径线的改变情况,以及通过独立样本t检验分析在不同年龄、性别、矫形时间、漏斗胸对称与否、是否合并脊柱侧弯等情况间的差异性。结果50例患儿均顺利完成矫形器置入术及矫形器拔除术,无明显术中及术后并发症,Nuss矫形后较矫形前相比,胸廓前后径在第8~12胸椎水平均较前增加,第3~5胸椎平面较前减小,胸廓横径在第8~10胸椎平面较前减小;年龄≤10岁、矫形时长≥2年及女性患儿胸廓前后径改变量在多个胸椎平面分别较年龄>10岁、矫形时长<2年及男性患儿大,P<0.05,差异具有统计学意义。结论漏斗胸Nuss矫形后前胸壁凹陷较前明显改善,并且在不同年龄和不同矫形时长间存在差异性,年龄较小及适当增加矫形时间可获得较好的矫形效果,而胸廓横径生长在一定程度上受限。     

Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Trigeminal neuralgia is a debilitating condition, and the pain easily spreads to other parts of the face. Here, we established a mouse model of partial transection of the infraorbital nerve (pT-ION) and found that the Connexin 36 (Cx36) inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia. Mefloquine reversed the pT-ION-induced upregulation of Cx36, glutamate receptor ionotropic kainate 2 (GluK2), transient receptor potential ankyrin 1 (TRPA1), and phosphorylated extracellular signal regulated kinase (p-ERK) in the trigeminal ganglion. Cold allodynia but not mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00594-4) contains supplementary material, which is available to authorized users.     

Exosomes from miRNA‐126‐modified endothelial progenitor cells alleviate brain injury and promote functional recovery after stroke

AimsWe previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXs^miR126) have enhanced efficacy.MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.ResultsWe found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXs^miR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery.     

eTEP inferior access with tailored retromuscular dissection for small to mid-sized umbilical hernia repair with or without inguinal hernia: early experience

Hernia - The minimally invasive surgical repair of combined inguinal and ventral hernias often requires shifting from one approach or plane to another. The traditional enhanced-view totally...