The mitochondrial seryl-tRNA synthetase SARS2 modifies onset in spastic paraplegia type 4

PurposeHereditary spastic paraplegia type 4 is extremely variable in age at onset; the same variant can cause onset at birth or in the eighth decade. We recently discovered that missense variants in SPAST, which influences microtubule dynamics, are associated with earlier onset and more severe disease than truncating variants, but even within the early and late-onset groups there remained significant differences in onset. Given the rarity of the condition, we adapted an extreme phenotype approach to identify genetic modifiers of onset.MethodsWe performed a genome-wide association study on 134 patients bearing truncating pathogenic variants in SPAST, divided into early- and late-onset groups (aged ≤15 and ≥45 years, respectively). A replication cohort of 419 included patients carrying either truncating or missense variants. Finally, age at onset was analyzed in the merged cohort (N = 553).ResultsWe found 1 signal associated with earlier age at onset (rs10775533, P = 8.73E-6) in 2 independent cohorts and in the merged cohort (N = 553, Mantel–Cox test, P < .0001). Western blotting in lymphocytes of 20 patients showed that this locus tends to upregulate SARS2 expression in earlier-onset patients.ConclusionSARS2 overexpression lowers the age of onset in hereditary spastic paraplegia type 4. Lowering SARS2 or improving mitochondrial function could thus present viable approaches to therapy.     

多模式神经电生理监测在颈椎前路手术中的预警意义

目的:探讨多模式神经电生理监测在颈椎前路手术中的预警意义。方法:2014年9月~2015年4月对53例行颈椎前路手术的颈椎病患者术中进行多模式神经电生理监测(A组),选取60例年龄、性别、病变节段和手术方式匹配但未进行神经电生理监测的颈椎前路手术患者作为对照(B组)。比较两组患者手术时间、术中出血量、神经根型颈椎病患者手术前后颈痛及上肢疼痛视觉模拟评分法(visual analogue scales,VAS)评分、颈部功能障碍指数(neck disability index,NDI)、脊髓型颈椎病患者术后JOA评分改善率和并发症的发生情况,分析A组病例中术中预警的类型和原因,以及与术前诊断、手术方式和手术节段之间的关系。结果:A组患者的手术时间为1.3±0.5h(0.8~2.1h),术中出血量为390±236ml(120~600ml),B组患者的手术时间为1.2±0.7h(0.6~2.4h),术中出血量为346±293ml(105~610ml),两组比较均无统计学差异(P0.05)。A、B两组神经根型颈椎病患者术前、术后的颈部和上肢VAS评分均无显著性差异(6.5±1.6 vs.6.8±1.4,7.6±2.4 vs.7.4±2.7,3.8±1.2vs.3.6±1.6,3.3±1.4 vs.3.9±1.8,P0.05),A组神经根型颈椎病患者术后NDI和脊髓型颈椎病患者JOA评分改善率明显优于B组[(19.2±7.1 vs 22.1±5.6,(84.1±10.3)%vs(73.3±9.2)%;P0.05]。在A组病例中,颈椎前路椎体次全切椎间融合手术较颈前路椎间盘切除椎间融合术的术中监测"严重预警"发生率更高(P0.05),但两种手术方式的"次要预警"发生率无显著性差异(P0.05);脊髓型颈椎病与神经根型颈椎病之间、单节段手术与双节段手术之间的术中监测"严重预警"和"次要预警"发生率均无统计学差异(P0.05)。结论:多模式神经电生理监测在颈椎前路手术中能及时预警神经损伤,可有效提高手术的安全性和临床疗效。     

新型上颈椎前路钩状钛板治疗寰枢椎不稳的生物力学测试

[目的]测试研究新型上颈椎前路钩状钛板治疗寰枢椎不稳的生物力学稳定性.[方法]采用上颈椎新鲜尸体标本6例依次参加5组试验:正常状态组、寰枢椎不稳组、新型上颈椎钩状钛板固定组、前路经寰枢关节螺钉固定组及后路Brooks钢丝固定组,利用SPSS 13.0软件包进行重复测量的方差分析,组间两两比较采用SNK检验法,差异标准置于0.05.[结果]前屈稳定性上,新型上颈椎钩状钛板组和Brooks组差异无显著性(P=0.525),但两者不如前路经寰枢关节螺钉组(P<0.05).后伸稳定性上,新型上颈椎钩状钛板组和前路经寰枢关节螺钉组差异无显著性(P=0.372),且两者稳定性明显强于Brooks组(P<0.05).侧屈上,前路经寰枢关节螺钉组与新型上颈椎钩状钛板组差异无显著性(P=0.216),且两者稳定性明显强于Brooks组.旋转稳定性上,前路经寰枢关节螺钉组优于新型上颈椎钩状钛板组,而后者又较Brooks组稳定性强(P<0.05).[结论]新型上颈椎前路钩状钛板具有一定的生物力学强度,其对于寰枢椎的稳定性弱于前路经寰枢关节螺钉,但明显强于Brooks,能够为寰枢椎不稳的病例提供可靠的固定强度.     

术前短期化疗对脊柱结核手术安全性的实验研究

目的通过巢式聚合酶链式反应（polymerase chain reaction,PCR）动态检测脊柱结核患者围手术期外周血的MTB-DNA的IS6110基因的含量,评估术前短期化疗对脊柱结核患者的手术安全性。方法根据IS6110基因设计两对特异性硫化修饰引物,结合高效保真聚合酶建立的巢式PCR,动态检测25例术前短期化疗的脊柱结核患者术前1天、术后1天、术后7天、术后14天外周血MTB-DNA的IS6110基因的含量变化,对外周血扩增产物IS6110基因含量进行比较分析。结果脊柱结核患者围手术期外周血IS6110基因含量变化的两种趋势：（1）15例患者伴随术后结核病灶的清除,外周血中的结核杆菌IS6110基因的从术后1天就开始逐渐减少;（2）10例患者术后1天时外周血中结核杆菌IS6110基因有短暂回升,但与术前1天外周血中结核杆菌IS6110基因含量比较无显著性差异（P〉0.05）,随着术后持续抗痨治疗,结核杆菌IS6110基因含量在术后1～2周均减少,均未发生结核杆菌血行播散并发症。结论如果脊柱结核患者一般情况好,术前短期化痨后行手术治疗安全有效。     

Segmental aneuploidies with 1 Mb resolution in human preimplantation blastocysts

PurposeThis study aimed to investigate the spectrum and characteristics of segmental aneuploidies (SAs) of <10 megabase (Mb) length in human preimplantation blastocysts.MethodsPreimplantation genetic testing for aneuploidy was performed in 15,411 blastocysts from 5171 patients using a validated 1 Mb resolution platform. The characteristics and spectrum of SAs, including the incidence, sizes, type, inheritance pattern, clinical significance, and embryo distribution, were studied.ResultsIn total, 6.4% of the 15,411 blastocysts carried SAs of >10 Mb, 4.9% of embryos had SAs ranging between 1 to 10 Mb, and 84.3% of 1 to 10 Mb SAs were <5 Mb in size. Inheritance pattern analysis indicated that approximately 63.8% of 1 to 10 Mb SAs were inherited and were predominantly 1 to 3 Mb in size. Furthermore, 18.4% of inherited SAs and 51.9% de novo 1 to 10 Mb SAs were pathogenic or likely pathogenic (P/LP). Different from whole-chromosome aneuploidies, reanalysis indicated that 50% of the de novo 1 to 10 Mb SAs and 70% of the >10 Mb SAs arose from mitotic errors.ConclusionBased on the established platform, 1 to 10 Mb SAs are common in blastocysts and include a subset of P/LP SAs. Inheritance pattern analysis and clinical interpretation based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines contributed to determine the P/LP SAs.     

微创切口和传统切口全髋关节置换临床疗效的系统评价

背景:目前对微创全髋关节置换的争议多集中在小切口术野有限,是否会增加股骨颈骨折、神经损伤等并发症及假体位置不良,影响手术远期疗效。目的:采用系统评价方法比较微创切口与传统切口全髋关节置换的临床疗效及安全性。方法:检索国内外微创切口与传统切口全髋关节置换的完全随机对照试验,严格评价纳入研究的方法学质量,并提取资料,采用RevMan5.1软件行Meta分析。结果与结论:共纳入10个随机对照试验,1001例患者。资料分析显示,微创切口与传统切口全髋关节置换在医源性神经损伤、髋臼杯外展角、股骨柄内翻和外翻发生率、置换后髋关节脱位率、再次手术率方面差异均无显著性意义。亚组分析表明:所有后侧入路的微创切口和传统切口全髋关节置换组在髋臼杯外展角、置换后髋关节脱位率和再次手术率方面差异无显著性意义。后外侧入路的微创切口和传统切口组置换后髋关节脱位率差异无显著性意义。表明微创切口和传统切口全髋关节置换两者疗效相当。     

Animal models for glucocorticoid-induced postmenopausal osteoporosis: An updated review

Glucocorticoid-induced postmenopausal osteoporosis is a severe osteoporosis, with high risk of major osteoporotic fractures. This severe osteoporosis urges more extensive and deeper basic study, in which suitable animal models are indispensable. However, no relevant review is available introducing this model systematically. Based on the recent studies on GI-PMOP, this brief review introduces the GI-PMOP animal model in terms of its establishment, evaluation of bone mass and discuss its molecular mechanism. Rat, rabbit and sheep with their respective merits were chosen. Both direct and indirect evaluation of bone mass help to understand the bone metabolism under different intervention. The crucial signaling pathways, miRNAs, osteogenic- or adipogenic- related factors and estrogen level may be the predominant contributors to the development of glucocorticoid-induced postmenopausal osteoporosis.     

单、双运动单元固定治疗胸腰椎骨折的疗效比较

 目的比较单运动单元与双运动单元固定治疗胸腰椎压缩性骨折及不完全爆裂骨折(AO分型为A1型和A3型)的疗效,探讨单运动单元固定的可行性。方法通过前瞻性研究方法,选取A1型和A3型胸腰椎骨折患者141例。按随机数字法将两型骨折患者随机分为单运动单元固定组和双运动单元固定组,A1型组分别为35例和26例,A3型组分别为41例和39例。通过腰功能评分及脊髓神经功能2000分级标准评估临床结果;通过测量术前、术后1周、终末随访时骨折椎楔变指数、骨折节段矢状指数评估影像学结果。终末评估时间设为术后18个月。结果141例患者均得到随访。单运动单元固定组平均出血量与手术时间均明显少于双运动单元固定组,差异有统计学意义。两种术式临床疗效无明显差异。A1型组,单运动单元固定组与双运动单元固定组椎体楔变矫正指数与终末随访矫正丢失率差异有统计学意义,前者优于后者。A3型组,两组差异均无统计学意义,但前者失败率大于后者,差异有统计学意义。结论单运动单元椎弓根钉-棒系统内固定治疗部分A1及A3型胸腰椎骨折,可取得与双运动单元固定相近甚至更佳的疗效,且有出血少、用时短等优点;对于A3.2型胸腰椎骨折,因其失败率较高须严格掌握适应证。