神经生长因子家族及其受体研究进展

过去几年在神经营养因子、受体和神经元细胞程序性死亡的研究领域中取得了几项引人注目的进展：（１）神经生长因子（ＮＧＦ）基因家族的其他一些成员包括脑源性神经营养因子（ＢＤＮＦ）、神经营养素－３（ＮＴ－３）、神经营养素－４（ＮＴ－４）、神经营养素－５（ＮＴ－５）的发现;（２）神经生长因子三维结构及功能和进化之关系的阐明;（３）定性了两种神经生长因子受体Ｐ７５＾ＮＧＦＲ和原癌基因ｐ１４０＾ｔｒｋＡ以及相关     

3D数字打印技术在重度脊柱侧弯中的临床分析研究

目的:评估和比较3D数字打印技术在重度脊柱侧弯患者手术中的临床疗效及安全性。方法:按照已经设定的纳入及排除标准,对2017年1月至2019年1月诊断为重度脊柱侧弯并在我科行手术治疗的22名患者进行前瞻性分析。根据是否采用3D打印技术辅助,将其通过随机数字表分为3D辅助组(实验组)与对照组。实验组(共11例)通过Minics软件进行3D模拟设计及打印,术中进行技术辅助。对照组(11例)则通过常规的徒手置钉办法进行手术。通过CT比较两组患者的置钉准确性,并比较两组患者的其他影像学检查和相关手术指标,包括:手术时间,输血量,透视次数等。结果:本研究纳入的患者(22例)均得到至少6个月的完整随访。两组患者在术前的影像学测评,Cobb角,年龄、性别构成等指标的比较中未见显著统计学差异(P>0.05)。实验组CT评价置钉准确率为83.6%(0级及1级),对照组的置钉准确率为72.3%。两组比较有统计学差异(P<0.05)。实验组在手术时间,术中输血量及透视次数等手术指标的比较中均显著优于对照组(P<0.05)。实验组的入院后待手术时间显著高于对照组(P<0.05)。实验组在术后3天的VAS指标显著优于对照组(P<0.05),但在术后6月的比较中无显著性差异(P>0.05)。两组患者的ODI指数较术前均有显著改善(P<0.05),且两组间无显著性差异(P>0.05)。两组患者均未出现严重并发症(P>0.05)。结论:与常规的徒手置钉相比,针对重度脊柱侧弯患者,3D数字打印辅助技术能够显著的提高置钉的准确性,减少手术时间和术中输血量,大幅度减少透视危害,且降低操作难度,值得临床进一步推广使用。     

后路减压内固定融合矫形治疗退变性腰椎侧凸伴椎管狭窄的临床研究

目的:探讨后路减压内固定融合矫形治疗退变性腰椎侧凸伴椎管狭窄的临床疗效。方法:将我院2009年1月~2015年1月收治的退变性腰椎侧凸伴椎管狭窄患者按照手术方法分为两组,实验组进行后路减压内固定融合矫形术治疗,对照组进行单纯后路减压固定矫形术治疗,对比两组患者术前、术后6个月和18个月的Cobb角、腰椎前凸角、日本骨科学会(JOA)评分、疼痛视觉模拟量表(VAS)情况,SRS-22国际标准量表评分情况以及出血量情况。结果:实验组术后18个月的Cobb角、腰椎前凸角分别为(16.8±5.16)°和(36.8±5.82)°,均分别低于对照组的(20.2±6.61)°和(41.2±5.67)°,且均低于术前(P0.05),而术前及术后6个月时两组比较无差异(P0.05);两组患者术后6个月和18个月的JOA评分、VAS评分比较均较术前明显改善(P0.05),且组间比较显示,术后18月两组比较均存在显著差异(P0.05);SRS-22国际标准评估量表显示,术后18个月两组患者的自理能力、自我评价、精神状态方面无显著差异(P0.05),而疼痛情况存在显著差异(P0.05)。两组术中出血量比较无统计学差异(P0.05)。结论:后路减压内固定融合矫形术治疗退变性腰椎侧凸伴椎管狭窄疗效显著,且后路减压内固定融合矫形术在改善患者的腰椎侧凸程度、功能障碍及疼痛程度方面优于单纯后路减压矫形内固定术,值得临床推广。     

根据退行性脊柱侧凸患者症状选择不同手术方案的临床研究

目的:探究根据退行性脊柱侧凸患者症状选择不同手术方案的治疗效果。方法:随机选取我院2007年9月到2015年10月收治的退行性脊柱侧凸患者124例,根据症状不同分A组和B组。A组62例患者腰背痛,接受长节段矫形内固定术;B组62例患者下肢症状明显,接受责任节段减压内固术。治疗期间记录两组手术时间、术中出血量、固定节段数及腰前凸角度,于治疗前、治疗后1个月以及末次随访时腰椎侧凸处的Cobb角,并采用视觉模拟评分法(VAS)和Oswestry功能障碍指数(ODI)评价患者疗效。结果:A组手术时间、出血量、固定节段数及腰前凸角度显著高于B组(P0.05);治疗后和末次随访两组患者VAS评分、ODI指数及Cobb角均有明显好转(P0.05),两组治疗后和末次随访之间的差异无统计学意义(P0.05)。结论:退行性脊柱侧凸在治疗时需根据患者具体症状选择不同的手术方案,长节段矫形内固定术耗时长、术中出血量多,在治疗时应谨慎,预防相关并发症的发生。     

LncRNA‐SULT1C2A regulates Foxo4 in congenital scoliosis by targeting rno‐miR‐466c‐5p through PI3K‐ATK signalling

Congenital scoliosis (CS) is the result of anomalous vertebrae development, but the pathogenesis of CS remains unclear. Long non‐coding RNAs (lncRNAs) have been implicated in embryo development, but their role in CS remains unknown. In this study, we investigated the role and mechanisms of a specific lncRNA, SULT1C2A, in somitogenesis in a rat model of vitamin A deficiency (VAD)‐induced CS. Bioinformatics analysis and quantitative real‐time PCR (qRT‐PCR) indicated that SULT1C2A expression was down‐regulated in VAD group, accompanied by increased expression of rno‐miR‐466c‐5p but decreased expression of Foxo4 and somitogenesis‐related genes such as Pax1, Nkx3‐2 and Sox9 on gestational day (GD) 9. Luciferase reporter and small interfering RNA (siRNA) assays showed that SULT1C2A functioned as a competing endogenous RNA to inhibit rno‐miR‐466c‐5p expression by direct binding, and rno‐miR‐466c‐5p inhibited Foxo4 expression by binding to its 3′ untranslated region (UTR). The spatiotemporal expression of SULT1C2A, rno‐miR‐466c‐5p and Foxo4 axis was dynamically altered on GDs 3, 8, 11, 15 and 21 as detected by qRT‐PCR and northern blot analyses, with parallel changes in Protein kinase B (AKT) phosphorylation and PI3K expression. Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno‐miR‐466c‐5p expression via the PI3K‐ATK signalling pathway in the rat model of VAD‐CS. Thus, SULT1C2A may be a potential target for treating CS.     

The retinol-retinoic acid metabolic pathway is impaired in the lumbar spine of a rat model of congenital kyphoscoliosis

Although congenital scoliosis is defined as a genetic disease characterized by a congenital and abnormal curvature of the spinal vertebrae, our knowledge of the genetic underpinnings of the disease is insufficient. We herein show that the downregulation of the retinol-retinoic acid metabolism pathway is involved in the pathogenesis of congenital scoliosis. By analyzing DNA microarray data, we found that the expression levels of genes associated with the retinol metabolism pathway were decreased in the lumbar spine of Ishibashi rats (IS), a rat model of congenital kyphoscoliosis. The expression of Adh1 and Aldh1a2 (alcohol dehydrogenase), two enzymes that convert retinol to retinoic acid in this pathway, were decreased at both the gene and protein levels. Rarα, a receptor of retinoic acid and bone morphogenetic protein 2, which play a central role in bone formation and are located downstream of this pathway, were also downregulated. Interestingly, the serum retinol levels of IS rats were higher than those of wild-type control rats. These results indicate that the adequate conversion from retinol to retinoic acid is extremely important in the regulation of normal bone formation and it may also be a key factor for understanding the pathogenesis of congenital scoliosis.     

Functional variants of hepatocyte growth factor identified in patients with adolescent idiopathic scoliosis

The genetic etiology of adolescent idiopathic scoliosis (AIS) remains obscure. Whole-genome sequencing was performed in four members of one family. Then, we performed a rigorous computational analysis to determine the deleterious effects of the identified variants. Furthermore, the structural differences between the native hepatocyte growth factor (HGF) protein and a protein encoded by an HGF variant containing one mutation (p.T596M) were analyzed using molecular dynamic stimulation. A novel heterozygous mutation (p.T596M) within the HGF gene was identified and found to cosegregate with scoliosis phenotypes in three affected family members. Subsequent modeling and structure-based analyses supported the theory that this mutation is functionally deleterious. Functional analyses demonstrated that the HGF p.T596 M mutation changed the ability of the HGF protein to be secreted and impaired migration and invasion in HEK293T cells. Furthermore, an HGF knockdown zebrafish model exhibited a curly tailed phenotype. Mutation in HGF is associated with an autosomal dominant pattern of inheritance of AIS. This finding increases our understanding of the genetic heterogeneity of AIS.     

LenkeⅡ型青少年特发性脊柱侧凸患者内固定冠状面失衡的相关因素分析

目的:探讨Lenke II型青少年特发性脊柱侧凸患者内固定冠状面失衡相关因素分析。方法:选取我院骨科已确诊为Lenke II青少年特发性脊柱侧凸患者60例,根据术前脊柱柔韧度、risser分级水平、支具支持治疗、椎体融合数、内固定系统选择等多方面影响因素对内固定后冠状面失平衡情况发生率进行分析评估,其数据结果应用统计学软件SPSS 17.0处理。结果:对术后患者评估比较,多种因素均可影响内固定后冠状面失平衡情况发生,表现为:脊柱柔韧度低、risser分级高、长时间支具佩戴、延长融合椎体范围、先进钉棒系统方案选择均可明显提高术后疗效,降低内固定后冠状面失平衡情况发生率(P0.05),其结果均有统计学意义。结论:临床上通过对患者脊柱柔韧度、risser分级情况评估来判断脊柱成熟度,并在术后积极支具辅助治疗,选用钉棒固定系统并延长融合椎体节段,可明显降低内固定后冠状面失平衡情况发生,提高远期随访疗效。     

腰椎多节段退变性滑脱的手术治疗

目的:研讨腰椎多节段退变性滑脱手术减压和植骨融合方式与疗效的关系。方法:20例腰椎多节段退变性滑脱患者行后路椎弓根螺钉复位内固定后,采用椎管减压、神经根松解,行椎间植骨和后外侧植骨融合术,采用日本整形外科学会(JOA)下腰痛评分标准评价疗效。结果:获得连续随访者18例,随访时间9月～3年,平均24个月,优良率90%。结论:可靠的内固定、复位,神经根松解,椎间植骨融合治疗腰椎多节段退变性滑脱效果满意,充分的神经根松解是手术治疗的关键。