| Background:Congenital scoliosis (CS) is a form of vertebral malformation, which is caused by defects in the development of somite to vertebra during embryogenesis. The exact cause of congenital scoliosis is still unkown, and may be associated with susceptible genes and environmental factors. Previous studies believed that genetic factors contribute to vertebral malformations, and there are still no reports about the molecular cause of congenital scoliosis.Surgery is the main method for the treatment of congenital scoliosis. Posterior hemivertebra resection can remove the main causes of spinal deformity and achieve excellent postoperative and follow-up correction results. However, there are still complications in the perioperative period and follow-up. So it is important to analyze the complications and find the strategies to prevent these complications.Objectives:PartⅠ1. To separate and identify the MSCs from bone marrow of CS and control healthy patients.2. Qualitative and quantitative analysis of proteins expressed in the MSCs of CS patients and its controls to find the differently expressed proteins (DEPs). Biological information analysis of DEPs was needed to find the role of DEPs in the onset and development of CS.Part IITo analyze the correction results of posterior hemivertebra resection and complications in the perioperative period and follow-up. And further study was needed to find risk factors associated with complications and find the strategies to prevent these complications.Methods:PartⅠ1. MSCs was isolated from bone marrow of 5 CS and 5 control patients., and further immunophenotyping and multilineage differentiation were performed to identify these isolated cells as MSCs.2. Protein were extracted and quantified from MSCs using Bradford methods. Qualitative and quantitative analysis of proteins expressed in the MSCs of CS and control patients were performed using iTRAQ technology, and we adopted a fold change cutoff ratio of≥1.20 or≤0.80 with p-value<0.05 to select differentially expressed proteins (DEPs).3. Biological information analysis of DEPs was performed based on Panther, Meta-core and KEGG databases to find the roles of DEPs in the onset and development of CS.4. Western blotting was used to validate the differential expression of these proteins in BM-MSCs of patients with the results from iTRAQ technology.Part ⅡSurgical results and complications were collected from patients with posterior hemivertebra resection from January 2003 to January 2012 in our medical center, and univariate analysis was conducted to identify risk factors associated with congstruct related complications. The strategies to prevent these complications were suggested based on the analysis of risk factors.Results:PartⅠAll the cultured cells from CS and control patients were identified as mesenchymal stem cells through osteogenic and adipogenic differentiation, and immunophenotype.Using iTRAQ technology, a total of 4622 proteins were identified from all the included patients, and 205 significantly differentially expressed proteins (DEPs) were identified using a fold change cutoff ratio of> 1.20 or<0.80 with p-value<0.05. And 22 DEPs were believed to be associated with the onset and progression of CS. These 22 DEPs was mainly associated with system development, nervous system development and anatomical structure morphogenesis, and might play their roles through signaling pathways, such as PI3K-Akt signaling pathway, and focal adhesion pathway.Part IIExcellent correction results were obtained in the perioperative period and follow-up, and 11 cases (9.48%) had complications, including 7 construct related complications (6.03%) and 4 non-construct related complications (3.45%). Through univariate analysis, cases with younger age (≤5 years old) (P=0.037), lumbar hemivertebra resection (p=0.016), or bisegmental fusion (p=0.029) were found to have a higher prevalence of construct/implant related complications than other cases with significant statistical differences. There was no significant difference in other potential risk factors.Conclusions:PartⅠMSCs can be isolated and expand-cultured from bone marrow through the whole bone marrow culture method.205 DEPs were identified between CS and control groups, and 22 DEPs were believed to be associated with the onset and progression of CS. These results may provide a new insight in further understanding the molecular mechanism of CS.Part IIPosterior hemivertebra resection is a safe and effective technique for congenital scoliosis with hemivertebra. However, complications still exist in peri-operative period and follow-up, and complications associated with implants is the commonest complications. Risk factors associated with implant failure include initial surgical age, lumbar hemivertebra and short fusion. Measures, such as careful preoperative evaluation and surgical plan with CT scan, sophisticated operation during surgery, usage of cage or cross-links to improve postoperative instant stability, protection in brace and regular follow-up postoperatively, should be taken to reduce implant related complication rate. |
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