| Part One 17?-Estradiol inhibits coccygeal intervertebral disc degeneration in a rat model via activating mTOR-mediated signaling pathwayObjective: Previous studies have reported that 17?-Estradiol(E2)can effectively inhibit the apoptosis of rat intervertebral disc cells induced by interleukin-1?(IL-1?)and TNF-?,but the mechanism has not been fully elucidated.The purpose of this study was to investigate the role of the mTOR?GSK-3??NF-?B pathways in 17?-estradiol protecting against intervertebral disc degeneration.Methods: Twenty 3-month-old female Sprague-Dawlay(SD)rats were randomly divided into four groups: sham,OVX,E2 and ICI.The sham group only underwent the resection of the fat.OVX group was treated by removing bilateral ovaries and needle puncture of caudal discs.E2 group was treated with E2 in addition to OVX and needle puncture.ICI group was treated with E2 and pretreated with ICI182780(estrogen receptor antagonist)in addition to OVX and needle puncture.Twenty-eight days later,Western blot was performed to determine the effect of E2 on the intervertebral disc degeneration and the role of mTOR,GSK-3 ? and NF-?B pathways.Previous experiments found that mTOR pathway is the main pathway of the E2 intervention in intervertebral disc degeneration.Then,thirty 3-month-old female SD rats were randomly divided into five groups: sham,OVX,E2,ICI and mTOR pathway inhibitor group(Rap group).The sham group,OVX group,E2 group and ICI group were treated as before.Rap group was treated with rapamycin(Rap,mTOR pathway inhibitor)in addition to OVX and needle puncture.Twenty-eight days later,the degenerative grades of intervertebral disc in all rats were evaluated by Western blot,immunohistochemistry(IHC),hematoxylin and eosin(HE)staining and X-ray.Twenty-four hours after the last administration with estrogen,X-ray imaging data were collected for all rats' coccygeal spine.Three rats in each group were randomly selected to take Co5/6 nucleus pulposus tissue and collect nucleus pulposus cells,then detected the expression of MMP-3,MMP-13 and cleaved Caspase-3 by Western blot.The remaining rats' Co5/6 were fixed in 4% paraformaldehyde for 24 hours and decalcified in 10% EDTA solution for 30 days.IHC and HE staining were used to evaluate the histological changes.Results: The initial Western blot results showed that cleaved Caspase-3 was significantly increased in OVX group compared with the sham group(P<0.05),which was reversed by E2(P<0.05).In the ICI group,cleaved Caspase-3 expression was significantly increased(P<0.05).We studied the role of three pathways,mTOR,GSK-3? and NF-?B/p65,in E2 intervention of disc degeneration.Compared with sham group,the expression of p-mTOR in OVX group significantly decreased(P<0.05),which can be increased by E2 administration(P<0.05).Nevertheless,estrogen receptor antagonist ICI182780 can reverse E2 effect(P<0.05).In contrast,there was no statistical difference regarding the change of p-P65 or p-GSK-3? expression(P>0.05).According to the results of Western blot,we found that mTOR pathway was responsible for the effect of E2 on intervertebral disc degeneration.In order to further confirm the role of mTOR pathway,we regulated mTOR expression using Rap and explored its effect on downstream Caspase-3,MMP-3 and MMP-13.As a result,Western blot showed that the p-mTOR expression in Rap group was markedly lower than that in E2 group(P<0.05).In addition,the expression of Caspase-3,MMP-3 and MMP-13 in Rap group was much more than that in E2 group(P<0.05).IHC assay showed that IL-6 positively expressed in nucleus pulposus cells and peripheral cells in OVX group;compared with OVX group,IL-6 expressed less in E2 group,but can be increased by ICI182780 and Rap.By contrast,the expression of type II COL was the opposite to IL-6.Histologically,compared with the sham group,the number of nucleus pulposus cells in OVX group was significantly reduced,and the tissue structure was damaged.In E2 group,the above phenomena were reversed.And the tissue structure in Rap group was relatively damaged with the decrease of the number of nucleus pulposus cells,and the boundary between nucleus pulposus and annulus was unclear.The histological scores of the above four groups were 1.313 ± 0.464,3.688 ± 0.768,1.750 ± 0.559 and 2.438 ± 0.496,respectively.The histological scores in Rap group were significantly higher than those in E2 group(P<0.05).Conclusion: This study shows that E2 can effectively inhibit the cell apoptosis and intervertebral disc degeneration(IVDD)via activating mTOR pathway.Part Two Radiographic Evaluation of Three Different Approach Intervertebral Fusion Techniques for the Treatment of Single Segment Lumbar Degenerative DiseasesObjectives: The aim of this study was to evaluate the radiographic results of oblique lateral interbody fusion,transforaminal lumbar interbody fusion and posterior lumbar interbody fusion for the treatment of single segment lumbar degenerative disease.Methods: In this study,201 patients,who underwent OLIF,TLIF or PLIF for treatment of single segment lumbar degenerative disease from Jan.2015 to Jan.2019,were retrospectively reviewed.Based on the type of lumbar interbody fusion,the patients were classified into 3 groups: OLIF group,TLIF group and PLIF group.Clinical and radiographic data of all patients were collected before and after operation.The relevant data included age,sex,BMI,smoking,drinking,heart disease,hypertension,diabetes,preoperative and postoperative VAS,preoperative and postoperative ODI,lumbar lordosis(LL),fusion segment lordosis(FSL),intervertebral space anterior height(ISH-A),intervertebral space posterior height(ISH-P),intervertebral space height change index(ISH-Index),foramen height(FH).All patients were followed up for 6 months to compare early radiographic results of different fusion patterns.All the data were analysed by SPSS software.Results: 79 patients were in OLIF group,38 patients were in TLIF group and 84 patients were in PLIF group.Compared with preoperative,OLIF group showed significant improvement in lumbar lordosis(P<0.001),fusion segment lordosis(P<0.001),foramen height(P<0.001),intervertebral space anterior height(P<0.001),intervertebral space posterior height(P<0.001),and the differences had statistically significant.Intervertebral space height change index in OLIF group was 1.24±0.21;TLIF group showed significant improvement in lumbar lordosis(P<0.001),fusion segment lordosis(P<0.001),intervertebral space anterior height(P<0.001),intervertebral space posterior height(P<0.001),foramen height(P<0.001),and the differences had statistically significant.Intervertebral space height change index in TLIF group was 1.20±0.16;PLIF showed significant improvement in intervertebral space anterior height(P<0.001),intervertebral space posterior height(P<0.001),foramen height(P<0.001),and the differences had statistically significant.Intervertebral space intervertebral space height change index was 0.64±0.11.However,compared with preoperative,PLIF group did not show significant difference in lumbar lordosis and fusion segment lordosis(P>0.05).Results of comparison between the three groups were as follow.Compared with TLIF and PLIF,OLIF had larger lumbar lordosis(P<0.05),fusion segment lordosis(P<0.05),intervertebral space anterior height(P<0.001),intervertebral space posterior height(P<0.001)and foramen height(P<0.05).Compared with PLIF,TLIF had larger lumbar lordosis(P<0.001),fusion segment lordosis(P=0.008),intervertebral space anterior height(P=0.002).However,PLIF group was better than the TLIF group in terms of intervertebral space posterior height(P<0.001)and foramen height(P<0.001).The results of intervertebral space height change index showed that OLIF group(P<0.001)and the TLIF group(P<0.001)were significantly higher compared with the PLIF group,however,there was no significant difference(P=0.471)between OLIF group and TLIF group.Conclusions: The three lumbar fusion methods of OLIF,PLIF and TLIF can achieve satisfactory clinical results.At the same time,OLIF in lumbar lordosis,fusion segment lordosis,intervertebral space anterior height,intervertebral space posterior height,foramen height has greater advantages.TLIF surgery is superior to PLIF in restoring the lumbar lordosis,fusion segment lordosis,but lower in improvement of intervertebral space posterior height and foramen height.Part Three Incidence and risk factors of posterior cagemigration following decompression and instrumented fusion for degenerative lumbar disordersObjective: The aim of this study was to explore the incidence and risk factors for posterior cage migration(PCM)following decompression and instrumented fusion for degenerative lumbar disorders,and hope to provide references in decision making and surgical planning for spine surgeons.Method: By retrieving the medical records from January 2011 to December 2015,286 patients were retrospectively reviewed.According to the occurrence of PCM,patients were divided into 2 groups: PCM group and non-PCM(N-PCM).To investigate risk values for PCM,3 categorized factors were analyzed statistically: patient characteristics: age,sex,body mass index,bone mineral density,duration of disease,diagnosis,comorbidity,smoke;surgical variables: surgery time,blood loss,surgical strategy,cage morphology,cage size,surgical segment,fusion number,source of bone graft,surgeon experience;radiographic parameters: preoperative lumbar lordosis,correction of lumbar lordosis,preoperative lumbar mobility,preoperative intervertebral height,change of intervertebral height,Modic changes,paraspinal muscle degeneration.Results: PCM was detected in 18 of 286 patients(6.3%)at follow-up.There was no statistically signifificant differencebetween the 2 groups in patient characteristics,except diagnosis,as lumbar spondylolisthesis was more prevalent in PCM group than that in N-PCM group.There was no difference between the 2 groups in surgical variables,except cage size and surgeon experience,as size of cage was smaller in PCM group than that in N-PCM group,and the surgeons with less experience(less than 3 years)were more prevalent in PCM group than that in N-PCM group.There was no statistically signifificant difference between 2 groups in radiographic parameters.Logistic regression model revealed that less than 3 years of surgeons' experience,small cage size,and lumbar spondylolisthesis were independently associated with PCM.Conclusion: For patients with lumbar spondylolisthesis,they should be fully informed about the risk of PCM before operation.While for spinal surgeons,large cage should be preferred,and careful manipulation should be adopted,especially for new learners with less than 3-year experience of fusion surgery. |
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