不同复发类型的马蹄内翻足应用Ponseti方法治疗过程和结果的差异及其机制的研究

发布时间：2018-05-13 04:20

本文选题：特发性马蹄内翻足 + 季节性　；参考：《上海交通大学》2014年博士论文

【摘要】：第一部分中国东南部特发性马蹄内翻足季节发病差异及该病与髋关节发育不良相关性的研究目的：国外一些研究表明，特发性马蹄内翻足发病率存在季节性差异。但是，很少有针对于中国特发性马蹄内翻足人群季节发病差异的研究。并且作为儿童科最为常见的两种疾病，先天性马蹄内翻足患儿中髋关节发育不良的发病率是否高于普通人群仍然存在争议。本研究意在探讨中国东南部地区特发性马蹄内翻足新生儿是否存在季节性发病差异，并且探讨这部分特发性马蹄内翻足中髋关节发育不良的发病率。方法：本研究回顾我院2009年至2013年门诊收治的所有马蹄内翻足患儿。季节发病差异研究的纳入标准：（1）临床诊断为特发性马蹄内翻足并且除外由他系统疾病引起的马蹄内翻足，如多关节挛缩、脊柱裂或脊髓脊膜膨出症；（2）2009年9月1日至2013年8月31日出生的患儿；（3）母亲妊娠期中早期居住地为中国东南六省市，包括浙江省、江苏省、上海市、安徽省、江西省和福建省；（4）足月产患儿；（5）汉族患儿。此外，本研究回顾我国第六次人口普查数据（2009-2010）。马蹄内翻足患儿髋关节发病率研究纳入标准：（1）临床诊断为特发性马蹄内翻足并且除外其他系统疾病，如多关节挛缩、脊柱裂或脊髓脊膜膨出症（2）2010年1月1日至2012年12月31日在我院就诊（3）就诊时年龄年龄小于6周（4）马蹄内翻足畸形未治疗。统计学方法包括卡方检验、Kruskal Wallis秩和检验及Wilcoxon秩和检验。所有统计数据均使用SAS9.2软件包（SAS Institutes, Cary, North Carolina, USA）进行分析，以p 0.05为有统计学差异。结果：共239名特发性马蹄内翻足患儿纳入季节发病差异的研究，包括177名男性患儿和62名女性患儿。239名患儿中224名在我院就诊前其马蹄内翻足畸形未接受过任何形式的治疗，仅有15名患儿接受过保守治疗。191名患儿为第一胎生产并且所有纳入研究患儿的母亲分娩年龄均在30岁以下。239名特发性马蹄内翻足患儿包括107例双侧马蹄内翻足和132例单侧马蹄内翻足，，其中包括81例右侧马蹄内翻足及51例左侧马蹄内翻足。然而对比我国2009年至2010年上述六省市各月份和季节新生人口数量发现，我们的特发性马蹄内翻足人群发病高峰在秋季。此外，我们并没有发现马蹄内翻足的严重程度随着季节更替而发生变化。此外，共184名患儿纳入马蹄内翻足中髋关节发病率的研究，所有184名患儿进行Graf方法髋关节超声检查。基于Graf方法超声分型和治疗方案，共5名患儿（4名女性患儿和1名男性患儿）被诊断为髋关节发育不良，本研究特发性马蹄内翻足患儿中髋关节发育不良的发病率为2.7%（5/184），但是5名髋关节发育不良的患儿和184名单纯马蹄内翻足患儿足畸形严重程度无统计学差异。结论：中国东南部地区特发性马蹄内翻足发病率呈季节性变化，秋季为发病高峰。考虑到纳入该研究的马蹄内翻足人群的民族、居住地及气候的一致性，这部分马蹄内翻足人群展现的季节发病差异可能与其遗传背景和居住地环境因素有关。此外，特发性马蹄内翻足新生儿人群中的髋关节发育不良的发病率高于正常新生儿人群，对于特发马蹄内翻足的新生儿应该进行髋关节超声的筛查。但是，决定马蹄内翻足严重程度的因素可能并不影响髋关节的发育。第二部分不同复发类型的马蹄内翻足采用Ponseti方法的治疗过程及治疗后功能评价目的：虽然广泛的后侧或后内侧软组织松解手术在很长一段时间内在先天性马蹄内翻足的治疗中占主要地位。但是长期随访研究显示这种方法治疗的马蹄内翻足常存在残留畸形且容易复发。即使未出现畸形复发也会存在疼痛、僵硬、关节活动受限等症状，甚至早发骨性关节炎表现。由于反复多次的松解手术会加重破坏关节结构和功能，本研究中我们尝试应用Ponseti方法治疗广泛的后侧或后内侧软组织松解手术后残留畸形或畸形复发的马蹄内翻足并采用三种评分系统评估治疗后足踝功能。此外，尝试探讨何种评分系统能够更全面客观的反映这种马蹄内翻足治疗后足踝的功能状况。方法：采用Ponseti方法治疗的特发性马蹄内翻足支具佩戴结束至少1年且年龄大于7岁的患儿纳入本研究。将病人分为三组，I组病人：新生儿马蹄内翻足1岁以下即开始Ponseti方法治疗且治疗过程中无复发；II组病人：Ponseti方法治疗后复发的马蹄内翻足再次采用Ponseti方法治疗；III组病人：广泛的后侧或后内侧软组织松解手术治疗后残留畸形或复发的马蹄内翻足转而采用Ponseti方法治疗。采集的病人信息包括：性别、马蹄内翻足侧别、出生日期、治疗病史、本次Ponseti方法治疗年龄、石膏固定次数。所有病人都佩戴同样的带有连杆的足外展支具，但是III组病人支具佩戴方案为前3个月全天佩戴，3个月后每日12-14小时佩戴1年。本研究采用三种马蹄内翻足评分系统评定治疗后足踝功能，包括Laaveg和Ponseti评分系统、国际马蹄内翻足研究小组的评分系统和Huang等的评分系统（J Bone Joint Surg Br.1999;81:858-62）。所有病人治疗和功能评估都由同一名医生进行。统计学方法包括方差分析、卡方检验及Mann-Whitney秩和检验。所有统计数据均使用SAS9.2软件包（SAS Institutes, Cary, North Carolina, USA）进行分析，以p 0.05为有统计学差异。结果：4人7足（3名男性1名女性患儿，3名双侧及1名右侧马蹄内翻足患儿）纳入I组；5人9足（3名男性2名女性患儿，4名双侧及1名左侧马蹄内翻足患儿）纳入II组；9人12足（6名男性3名女性患儿，3名双侧及6名单侧马蹄内翻足患儿，包括4名左侧和2名右侧马蹄内翻足）纳入III组。I组患儿平均年龄、本次Ponseti治疗年龄及石膏次数分别为7.3，0.3及4.4；II组患儿为7.8，2.4及4.3；III组患儿为9.8，7.2及7.3。统计学分析发现I组和III组病人的石膏固定次数及II组和III组病人的石膏固定次数均存在显著统计学差异。三个组的病人本次Ponseti方法治疗年龄两两比较均有统计学差异。I组病人和II组病人共16足，其中12足在三个评分系统的结果均为优秀（Excellent），I组病人和II组病人仅各一名双侧马蹄内翻足病人共4足采用Laaveg和Ponseti评分系统的结果为良好（Good）。III组病人共12足采用Laaveg和Ponseti评分系统的评分结果3足为优秀（Excellent）、8足良好（Good）、1足一般（Fair），采用国际马蹄内翻足研究小组（ICFSG）的评分系统的评分结果8足良好（Good）、4足一般（Fair），采用Huang等的评分系统的评分结果12足均为良好（Good）。无论采用何种评分系统进行功能评估，III组病人足踝功能均差于I组和II组病人，但是I组和II组病人的足踝功能评分无差异。此外，对III组病人进行功能评估时，三个评分系统的功能评估结果一致性较差。结论：虽然需要更多的石膏固定次数和更长的治疗周期，本研究结果显示进行过广泛的后侧或后内侧软组织松解手术后残留畸形或者畸形复发的马蹄内翻足转而采用Ponseti方法治疗仍然可以恢复基本正常的足踝外形，同时避免了进一步破坏足踝软骨、骨骼及周围软组织。然而，恢复正常的足踝外形不代表恢复了正常的足踝功能。此外，由于Laaveg和Ponseti评分系统主观评分过多并且Huang等的评分系统各项评分的分值不够精细，我们推荐采用国际马蹄内翻足研究小组（ICFSG）的评分系统对进行过广泛的后侧或后内侧软组织松解手术后残留畸形或者畸形复发的马蹄内翻足转而采用Ponseti方法治疗后的足踝功能进行评估。第三部分软组织松解手术后复发的马蹄内翻足采用Ponseti方法治疗过程及治疗后功能差异机制的初步研究目的：进行过广泛软组织松解手术后残留畸形或者畸形复发的特发性马蹄内翻足转而采用Ponseti方法治疗需要更多的石膏固定次数和更长的治疗周期。虽然通过系统的治疗可以恢复基本正常的足踝外形，却无法恢复正常的足踝关节及跗骨间关节的活动度和功能。本研究从分子生物学和影像学骨骼三维重建分析两方面初步探讨造成这类马蹄内翻足治疗过程及结果差异可能的机制。方法：取材特发性马蹄内翻足松解手术中切除的距舟关节及跟骰关节韧带进行成纤维细胞原代培养。2名患儿的距舟及跟骰韧带组织原代培养的成纤维细胞在FX-5000细胞牵张拉伸应力加载系统中分别施加持续8h和16h20%拉伸长度牵拉刺激及持续48h和96h10%拉伸长度牵拉刺激，对应力刺激前后的细胞进行COL1A1、COL1A2、COL3A1、α-SMA、TNC、vimentin、TGF-β1、TGF-β2及TGF-β3的Real-time PCR检测以及vimentin和COL3A1的Western-blot检测，并透射电子显微镜观察刺激前后细胞内质网及核糖体的变化情况。此外，各随机选取1名同年龄的Ponseti方法治疗未经历复发的马蹄内翻足患儿及1名Ponseti方法治疗松解术后复发的患儿进行矢状位T1和T2信号的3.0T足踝核磁共振平扫。平扫层厚2mm，层距1mm，每名患儿每个序列共20层平扫图像。在Mimics v10.01软件中分别勾勒距骨和胫腓骨下段骨骼轮廓并重建骨骼三维模型。导入Imageware v13.2软件后沿踝关节屈伸运动轴背屈方向转动重建后的距骨模型25°，分析移动前后的距骨在冠状面旋后及水平面外旋的角度。统计学方法：单因素方差分析。所有统计数据均使用SAS9.2软件包（SASInstitutes, Cary, North Carolina, USA）进行分析，以p 0.05为有统计学差异。结果：Real-time PCR实验结果发现：8h和16h20%拉伸长度的牵拉刺激下，本研究检测的基因表达均未出现稳定的下调，但是COL-III、vimentin和TGF-β3的mRNA在10%拉伸长度牵拉刺激下超过48h以后开始表现出稳定的表达下调。并且western-blot实验中COL-III和vimentin蛋白在10%拉伸长度牵拉刺激下超过48h后同样出现表达下调。此外，透射电子显微镜研究发现内质网的扩张程度及核糖体的肿胀程度在10%拉伸长度牵拉刺激96h后均有明显缓解。采用Ponseti方法治疗成功未经历复发的患儿足踝骨骼三维重建模型（模型I）的踝关节屈伸运动轴倾斜角为13.9°，采用Ponseti方法治疗松解术后复发的患儿畸形矫正后足踝骨骼三维重建模型（模型II）的踝关节屈伸运动轴倾斜角为7.2°。距骨沿踝关节屈伸运动轴背屈方向转动25°后，模型I的距骨在冠状面旋后的角度为9.1°，同时在水平面外旋的角度为4.5°；模型II的距骨在冠状面旋后的角度为3.7°，同时在水平面外旋的角度为2.7°。结论：较长时间、较小拉伸长度的静态牵拉更能有效地降低进行过广泛的软组织松解手术的特发马蹄内翻足挛缩的软组织成纤维细胞的COL-III和vimentin等细胞外基质表达，TGF-β信号通路可能参与了松解手术后复发特发马蹄内翻足采用Ponseti方法治疗中这些细胞外基质的表达的调控。软组织松解手术的特发性马蹄内翻足踝关节屈伸运动轴倾斜角减小，踝关节活动受限的可能是距骨形态改变影响了踝关节屈伸运动轴倾斜角而造成的。
[Abstract]:Study on the difference of seasonal onset and the correlation between the disease and the dysplasia of the hip joint in the first part of the idiopathic horseshoe crab in the southeast of China

Objective : Some studies abroad have shown that there is a seasonal difference in the incidence of idiopathic horse - hoof turnover . However , there is little study on the prevalence of hip dysplasia among children with idiopathic horseshoe crab . The study is intended to explore the seasonal difference of hip dysplasia in children with idiopathic horseshoe crab in southeastern China , and to explore the incidence of hip dysplasia in the idiopathic horseshoe crab .

Methods : This study retrospectively reviewed the inclusion criteria of seasonal onset differences in all patients hospitalized in our hospital from 2009 to 2013 : ( 1 ) clinical diagnosis was idiopathic horseshoe - pronation with the exception of hoof - pronation caused by his system disease , such as multi - joint contracture , bifida bifida or meningocele ;
( 2 ) Children born from September 1 , 2009 to August 31 , 2013 ;
( 3 ) The early place of residence in the mother ' s pregnancy is six provinces and cities in Southeast China , including Zhejiang , Jiangsu , Shanghai , Anhui , Jiangxi and Fujian provinces ;
( 4 ) Children with full - term birth ;
( 5 ) Children with Han nationality . In addition , this study reviewed the sixth population census data in China ( 2009 - 2010 ) . The study included standard : ( 1 ) The clinical diagnosis was idiopathic horseshoe and other system diseases , such as multi - joint contracture , spinal bifida or spinal meningocele ( 2 ) were not treated in our hospital from January 1 , 2010 to December 31 , 2012 . Statistical methods include chi - square test , Kruskal ' s rank sum test and Wilcoxon rank sum test . All statistical data were analyzed using SAS9.2 software package ( SAS Institutes , Cary , North Carolina , USA ) , with a statistically significant difference of p 0.05 .

Results : A total of 239 children were enrolled in the study of seasonal onset , including 177 male children and 62 female children . Among the 239 children , 224 were treated with conservative treatment .

Conclusion : There is seasonal change in the incidence of idiopathic horseshoe crab in the southeast of China , which is the peak in autumn . Considering the national , place of residence and climate consistency , the incidence of hip dysplasia may be related to the genetic background and environmental factors . In addition , the incidence of hip dysplasia among the infants with idiopathic horseshoe crab is higher than that of the normal newborns . However , the factors that determine the severity of intra - horseshoe turn - over may not affect the development of the hip joint .

Treatment course and post - treatment function evaluation of Ponseti ' s method in the second part with different recurrence types .

Objective : Although extensive posterior or posterior soft tissue release surgery is a major role in the treatment of congenital clubfoot over a long period of time .

Methods : The Ponseti method was used to treat patients with idiopathic horseshoe pronation with end at least 1 year and older than 7 years old . The patients were divided into three groups , group I : the newborn horseshoe was turned over 1 year old , the Ponseti method was started and no recurrence occurred during the treatment .
Group II patients : Ponseti was treated with Ponseti method again after Ponseti ' s treatment .
Group III patients : extensive posterior or posterior internal soft tissue release surgery for residual deformity or recurrent horseshoe turn - over to Ponseti ' s method . The patient information collected includes : sex , intra - horseshoe roll - over , date of birth , medical history , the Ponseti method treatment age , the number of plaster fixations . All patients wear the same foot abduction brace with links , and 3 months after 3 months of wear for 1 year . This study evaluated the post - treatment ankle function with three horse - hoof roll - over scoring systems ( J Bone Joint Surg Br . 1999 ; 81 : 858 - 62 ) . All patient treatment and functional assessments were performed by the same doctor . Statistical methods included variance analysis , chi - square test and Mann - Whitney rank and test . All statistical data were analyzed using SAS9.2 software package ( SAS Institutes , Cary , North Carolina , USA ) , with a statistically significant difference of p 0.05 .

Results : 4 patients ( 3 men , 1 female , 3 bilateral and 1 right horseshoe crab ) were included in group I ;
Five patients ( 3 men , 2 female , 4 bilateral and 1 left foot - hoof children ) were included in group II ;
Nine out of 12 children ( 6 men , 3 women , 3 bilateral and 6 children with horseshoe pronation , including 4 left and 2 right horseshoe crabs ) were included in group III . The average age of children in group I was 7.3 , 0.3 and 4.4 , respectively .
The children in group II were 7.8 , 2.4 and 4.3 ;
In group III patients , there were significant differences in the number of plaster fixation in group I and group III patients and the number of plaster fixation in group II and group III . The results of the scoring system of group I and Ponseti were excellent ( Good ) , 4 - foot general ( Fair ) and Huang et al .

Conclusion : Although more plaster fixation times and longer treatment cycles are needed , the results of this study have shown that after extensive posterior or posterior internal soft tissue release surgery , residual deformity or recurrent deformity of the ankle can be recovered by Ponseti method , while avoiding further damage to the ankle cartilage , bone and surrounding soft tissue . However , the normal ankle profile does not represent the restoration of normal ankle function .

A preliminary study on the mechanism of Ponseti ' s treatment and post - treatment functional difference after soft tissue release in the third part .

Objective : To study the activity and function of foot ankle joint and tarsal joint in patients with residual deformity or recurrent deformity after extensive soft tissue lysis .

Methods : The primary culture of primary cultured fibroblasts was carried out in primary culture of idiopathic horseshoe crab . The results showed that the distance between the two groups was 2 mm and 20 % . The results showed that all the statistical data were analyzed by SAS9.2 software package ( SASW , Cary , North Carolina , USA ) .

Results : The results showed that the expression of COL - III , vimentin and TGF - 尾3 had no stable downregulation at 10 % elongation at 10 % .
Conclusion : For a long time , the static traction of small tensile length can effectively reduce the expression of COL - III and vimentin in soft tissue fibroblasts , such as COL - III and vimentin of soft tissue fibroblasts .

【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R726.8

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