Expression Of VEGF Is Associated With Autophagy Induced Intervertebral Disc Degeneration In Rat Nucleus Pulposus And Clinical Radiographic Evaluation Of Scoliosis

Chapter 2(Section 1)Introduction:Intervertebral disc degeneration(IDD)is the initiating factor of degenerative lumbar disease.The normal intervertebral disc is avascular tissue.In degenerative condition,and the expression of VEGF increases,and the angiogenesis of the newborn arterioles appears.Autophagy may play a "double-edged sword" in the process of intervertebral disc degeneration,which may promote or inhibit the degeneration.At present,the mechanism of the effect of VEGF on the degeneration of intervertebral disc is not clear.In this study,we discussed possible relationship between neovascularization(VEGF),autophagy and intervertebral disc degeneration at the model animal level.Methods:In our study,60 healthy 3 month old SD rats were divided into 4 groups with bilateral ovariectomy.Group A was a sham operation group;group B underwent bilateral ovariectomy;group C underwent bilateral ovariectomy with estrogen injection;group D was bilateral ovariectomy with autophagy inhibitor 3-methyl adenine(3-MA)injection.The weight of the rats was recorded.After 6 months of feeding,rats were sacrificed,the nucleus pulposus of lumbar intervertebral disc was harvested.The tissue samples were cryopreserved at-80?.The protein was extracted,and the expression of VEGF-A,phosphorylated mTOR,autophagy related protein Beclin-1 and LC3 were detected by Western Blot.The degeneration and autophagy of intervertebral disc in each group were determined by HE staining and immunohistochemical staining.The expression of autophagosomes in four groups of rats were observed by scanning electron microscope.Results:There was no significant difference between four groups of rats in each time point of weight monitoring(P>0.05).With the increase of feeding time,the weight of the rats increased significantly.After bilateral ovariectomy,the results of HE staining and immunohistochemical staining showed that the degeneration of intervertebral disc in group B and group D was more obvious than that in group A and C group.The results of scanning electron microscopy showed that there were more autophagosomes in the nucleus of the intervertebral disc of the A and C rats,indicating that the autophagy level was higher in the two groups.The results of immunohistochemistry and Western Blot were in agreement with the results of scanning electron microscope.In severe B group and D group,the expression level of VEGF in nucleus pulposus was higher than that in A group and C group,suggesting that VEGF expression may inhibit autophagy of nucleus pulposus by activating mTOR signal pathway in A group and mTOR group.Conclusions:Intervertebral disc degeneration occurred after bilateral ovariectomy in rats.However,more neovascularization was found in the degenerative intervertebral disc,the expression of angiogenic factors increased and the level of autophagy decreased significantly.The mechanism may be the neovascularization in the process of degeneration,which activates the mTOR signaling pathway,suppresses the autophagy process of the nucleus pulposus cells,and accelerates the degeneration of the intervertebral disc.Chapter 3Section 1.Mismatch between proximal rod contouring and proximal junctional angle:A predisposed risk factor for proximal junctional kyphosis in degenerative scoliosisIntroduction:Proximal junctional kyphosis(PJK)is one of the complications in the treatment of degenerative scoliosis,the post-operative PI-LL mismatch and the increased rod stiffness are supposed to be the etiology of PJK.However,the impact of rod contouring on PJK has not been fully illustrated.The objective of this study was to investigate whether the mismatch between proximal junctional angle(PJA)and the proximal rod contouring contributed to the occurrence of post-operative PJK in degenerative scoliosis.Methods:A retrospective study was performed on 27 consecutive degenerative scoliosis patients(3 males and 24 females)who underwent corrective surgery with more than 2-year follow-up.Radiographic parameters included proximal rod contouring angle(PRCA)and PJA at the three time-points.The subjects were divided into two groups:PJK group and non-PJK group with the definition of PJK as a PJA>10 degrees.The mismatch between PRCA and post-op PJA,defined as the difference between PRCA and post-op PJA of more than 5 degrees,was then compared between PJK and non-PJK group.Results:The patients' mean age was 60.48 ± 6.47 years old with a mean Cobb angle of 40.89 ± 14.33°.12 patients,with a mean PJA of 18.67 ± 5.31° at the last follow-up,were stratified into the PJK group,while the remaining 15 patients,with a mean PJA of 5.33 ± 2.47,were placed into the non-PJK group.A significant difference in the mismatch between post-op PJA and PRCA was observed between PJK and non-PJK group(8.83 ± 5.07°vs 4.07 ± 2.91°,P=0.005).Meanwhile the difference of mismatch between pre-op PJA and PRCA showed no statistical significance(5.16 ± 4.24° vs 3.00 ± 2.48°,P=0.109).Conclusions:Mismatch between rod contouring and post-operative proximal spinal curve may be a predisposed risk factor for PJK during follow-ups in degenerative scoliosis.Section 2.Is the surgical restoration of lumbar alignment different between patients with the idiopathic lumbar scoliosis and degenerative lumbar scoliosis?Introduction:The objective of this study was to compare the surgical restoration of lumbar sagittal alignment between patients with idiopathic lumbar scoliosis(ILS)and degenerative lumbar scoliosis(DLS).Methods:A retrospective study of 62 consecutive adult patients with lumbar scoliosis from January 2009 to June 2013 in our center was performed,including 33 ILS cases(7 males and 26 females)and 29 DLS cases(1 male and 28 females).Long-cassette standing upright postero-anterior and lateral radiographs of the spine and pelvis were taken before and two weeks after surgeries.The pre-and post-operative parameters including lumbar lordosis(LL),pelvic incidence(PI),and Lumbo-femoral angle(LFA)were measured.Analysis the improvement of LL,PI-LL and LFA in both 2 groups.Results:Patients in ILS group have smaller PI-LL and LFA as well as a larger LL than in DLS group before surgeries.In DLS group,significant improvement was observed in terms of LL,PI-LL and 'LFA after surgeries.Meanwhile in ILS group,there were no significant differences between pre-operative LL,PI-LL and LFA and post-operative corresponding parameters.More significant improvements were observed in DLS-patients after surgery and the sagittal alignment were close to normal.Conclusion:The surgery can improve the lumbar sagittal alignment in both 2 groups.More significant improvements were observed in DLS patients and the sagittal alignment close to normal.Whereas the ILS patients have a good sagittal balance before surgery and required less restoration.Section 3.Halo-gravity traction combined with assisted ventilation:an effective pre-operative management for severe adult scoliosis complicated with respiratory dysfunctionIntroduction:Despite the improvements of surgical techniques and instrumentations for treatment of scoliosis,the management of severe and rigid scoliosis remains a major challenge.The purpose of this study was to investigate the change of pulmonary function in adult scoliosis patients with respiratory dysfunction undergoing HGT combined with assisted ventilation.Methods:21 adult patients were retrospectively reviewed with a mean age of 26.2 years.Inclusion criteria were as follows:age over 18 years old;coronal Cobb angle greater than 100°;with respiratory failure;and duration of HGT more than 1 month.All patients underwent respiratory training.Results:The Cobb angle averaged 131.21° and was reduced to 107.68° after HGT.Significantly increased mean forced vital capacity(FVC)was found after HGT(P=0.003)with significantly improved percent-predicted values for FVC(P<0.001).Meanwhile,significantly increased forced expiratory volume in.1s(FEV1)was also observed(P<0.001)with significantly improved percent-predicted values for FEV1(P = 0.003)after HGT.Conclusion:The results of our study revealed that combined HGT and assisted ventilation would be beneficial to pulmonary function improvement in severe adult scoliosis cases,most of which were young adults.Chapter 4Section 1.Sagittal profile response of cervical spine to the posterior correction of thoracic and lumbar adolescent idiopathic scoliosis:its correlated with the thoracic kyphosis?Introduction:Sagittal alignment of thoracic and lumbar spine and its vital association with quality of life have been well documented,while the compensation of cervical spine on sagittal plane in AIS patients with different curve patterns remains unclear.This study aims to analyze postoperative changes of cervical alignment in AIS patients with different curve patterns.Methods:Radiographic data were retrospectively reviewed in 43 AIS patients with right thoracic major curve vs 39 with major lumbar curve with a minimum of 2-year follow-up.Radiographic parameters analyzed in this study including cervical sagittal parameters(cervical lordosis(CL),T1 slope,TS-CL,T1-Spi,TPA and C2-C7 SVA)and spinopelvic sagittal parameters(PI,PT,SS,TK,LL,C7-S1 SVA,PI-LL)obtained from standardized full length standing PA and Lateral radiographs.Paired t tests were used for comparison with 0.05 as statistical significant threshold.Results:No significant differences in the mean age and follow up time were noticed between thoracic and lumbar AIS(L-AIS)groups.At baseline,larger cervical lordosis(5.69° VS.-5.12°,p=0.002)and smaller TS-CL(9.26° VS 17.09°,p=0.001)was noted in L-AIS patients,while pre-op TK showed no difference between two groups.When the immediate post-op sagittal profiles were compared between two groups,larger TK(23.72° VS.18.86°,p=0.009)and more obvious cervical lordosis(7.26° VS-2.60°,p=0.001)were noticed in L AIS group.During the follow up,larger TK and CL were still maintained in L-AIS group.In addition,a significant correlation was found between the improvement of CL and TK restoration in L-AIS patients(r=-0.473,p=0.002).Conclusion:Correlations between the improvement of cervical lordosis and thoracic kyphosis highlighted the importance of restoration of normal TK in AIS patient.Reciprocal change of cervical alignment may happen if the thoracic kyphosis was also simultaneously restored in AIS patients.For patients with different curve patterns,the cervical sagittal parameters tend to be similar during follow-up.