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The Screening Study Of Serum MicroRNA Signatures As An Early Diagnostic Molecular Marker For Ankylosing Spondylitis And The Imaging Study On Ankylosing Spondylitis

Posted on:2016-01-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:M L JiFull Text:PDF
GTID:1364330461958157Subject:Surgery
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Chapter 1 Identification of serum miR-146a and miR-155 as novel noninvasive biomarkers for ankylosing spondylitisObjective:To investigate differentially expressed serum microRNAs(miRNAs)between ankylosing spondylitis(AS)patients and controls,and to evaluate the potential of these miRNAs as biomarkers for AS.Method:An initial screening of miRNA expression by Solexa sequencing was performed using serum samples pooled from 10 AS patients and 10 controls,respectively.Subsequently,differential expression was validated using hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction(qRT-PCR).Furthermore,according to the severity of thoracolumbar kyphosis,AS patients were divided into group A(kyphosis<70°)and group B(kyphosis>70°).Disease activity and functional status were evaluated by Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)and the Bath Ankylosing Spondylitis Functional Index(BASFI),respectively.The areas under the receiver operating characteristic(ROC)curves of identified miRNAs were analyzed.Results:The results of Solexa sequencing indicated that 19 serum miRNAs were differentially expressed in AS patients compared with controls.Following qRT-PCR confirmation,miR-146a and miR-155 were significantly up-regulated in the sera of AS patients when compared with controls.The areas under the ROC curves using miR-146a and miR-155 were 0.917 and 0.964,respectively.Importantly,the miR-155 expression level in group B was significantly higher than that in group A.Additionally,significant correlation was observed between miR-155 expression level and BASDAI(r=0.5,p<0.01).Conclusion:Detection of serum miRNAs(miR-146a and miR-155)may serve as novel complementary biomarkers for AS.Moreover,the expression level of miR-155 is suggested to be associated with disease activity and the severity of thoracolumbar kyphosis secondary to AS.Chapter 2 Change of aortic length after closing-opening wedge osteotomy for patients with ankylosing spondylitis with thoracolumbar kyphosisObjective:To investigate the change in aortic length in ankylosing spondylitis(AS)patients with thoracolumbar kyphosis following closing-opening wedge osteotomy(COWO).Method:A total of 21 consecutive AS patients with a mean age of 38.9 years undergoing COWO for the correction of thoracolumbar kyphosis were retrospectively reviewed.Radiographical measurements included global kyphosis(GK),thoracic kyphosis(TK),lumbar lordosis(LL),angle of fusion levels(AFL),local kyphosis(LK)and anterior height of the osteotomized vertebra(AHOV).Both preoperative and postoperative sagittal 2D-reconstruction CT images of the spine were used to measure aortic length(the length between the superior endplate of the upper instrumented vertebra and the inferior endplate of L4).Results:There was an average 2.2 cm increase of aortic length postoperatively.Significant differences were observed in terms of the improvements of GK,LK,AFL,LL and anterior height of the osteotomized vertebra(P<0.01).The alteration of aortic length showed significant correlations with the change of GK(r=0.525,P=0.015),LK(r=0.654,P=0.001),AFL(r=0.634,P=0.002),and LL(r=0.538,P=0.012).Conclusion:The aorta lengthening after COWO was quantitatively confirmed by this study.With the correction of kyphosis,the aorta would be lengthened.Spine surgeons should be aware of the potential risk for the development of aortic injury in AS patients undergoing COWO for thoracolumbar kyphosis.Chapter 3 Change in abdominal morphology after surgical correction of thoracolumbar kyphosis secondary to ankylosing spondylitis:a computed tomographic studyObjective:To investigate the change in abdominal morphology in surgically treated ankylosing spondylitis(AS)patients with thoracolumbar kyphosis.Method:A total of 29 AS patients undergoing lumbar pedicle subtraction osteotomy for correction of thoracolumbar kyphosis were retrospectively reviewed.Computed tomographic scans of the spine were used to measure the longitudinal,transverse and anterior-posterior diameters of the abdominal cavity.Furthermore,the abdominal cavity was considered as an ellipsoid structure,thereby allowing calculation of its volume.Radiographic evaluations included global kyphosis(GK),thoracic kyphosis(TK),lumbar lordosis(LL),and angle of fusion levels(AFL).Results:The longitudinal diameter of abdominal cavity significantly increased(P<0.01),whereas the transverse and anterior-posterior diameters of the abdominal cavity did not change,postoperatively(P>0.05).Significant changes in GK,LL and AFL were observed(P<0.01).The abdominal cavity volume(ACV)increased by an average of 652 ml.The change in ACV was significantly correlated with the changes in GK(r=0.453,P=0.014),LL(r=0.42,P=0.023),and AFL(r=0.388,P=0.037).Conclusion:The increased ACV after correction of thoracolumbar kyphosis was quantitatively confirmed by this study.Thus,the improvement in digestive function after correction of thoracolumbar kyphosis secondary to AS,which has been previously documented,may be due to an increase in ACV.Moreover,spine surgeons should be aware of the potential risk for the development of abdominal complications caused by the lengthening of longitudinal diameter of the abdominal cavity.Chapter 4 The influence of osteotomy on sagittal spino-pelvic alignment in ankylosing spondylitis patients with thoracolumbar kyphosis:a comparison between Smith-Petersen osteotomies and pedicle subtraction osteotomyObjective:To compare the effects of Smith-Petersen osteotomies(SPOs)and pedicle subtraction osteotomy(PSO)on sagittal spino-pelvic balance in patients with thoracolumbar kyphosis secondary to ankylosing spondylitis(AS).Methods:Thirty-nine AS patients with thoracolumbar kyphosis underwent SPOs or PSO between August 2000 and June 2010 were retrospectively reviewed.According to the types of osteotomies,39 patients were categorized into 2 groups.Of them,15 patients(13male and 2 female,average age,28.1±7.1 years)were in the SPOs group,whereas 24 patients(20 male and 4 female,average age 38.3±7.9years)were in the PSO group.Radiographical parameters were measured and compared between the 2 groups.Radiographical measurements included thoracic kyphosis(TK),lumbar lordosis(LL),global kyphosis(GK),sagittal imbalance(SVA),pelvic incidence(PI),sacral slope(SS)and pelvic tilting(PT).Results:Significant differences were observed in terms of the improvement of LL,PT,SS,SVA and GK(P<0.05).Preoperatively,there was significant difference in PI and LL between the two groups(P<0.05).Postoperatively,significant differences were noted in LL,GK,PT and SS between the two groups(P<0.05).With respect to the mean loss of correction of GK,LL,SVA,PT and SS,significant differences were observed between two groups at the last follow-up(P<0.05).Conclusion:Compared with SPOs,satisfactory reconstruction of spino-pelvic alignment can be obtained by PSO.Loss of correction occurred frequently in SPOs.Additionally,optimum surgical strategy should be adopted according to the preoperative PI to achieve an optimal spino-pelvic realignment.Chapter 5 Comparison of clinical characteristics and life quality in ankylosing spondylitis(AS)-related thoracolumbar kyphosis between male and female patientsObjective:To investigate differences in AS-related thoracolumbar kyphosis between male and female patients in terms of clinical characteristics and life quality.Methods:From May 2009 to February 2013,51 AS patients(31 males and 20 females)with an average age of 40.6 years(21-62 years)were included in the study.All patients completed ODI,BASDAI,BASFI,BASMI,BAS-G,BASRI and SF-36.Additionally,age at onset,disease duration,ESR,CRP and HLA-B27 was recorded.Sagittal parameters were measured on standing lateral full-spine radiographs,including TK,GK,LL,SVA,PI,PT and SS.A comparison was conducted in terms of age at onset,disease duration,ESR,CRP,HLA-B27,TK,LL,GK,SVA,PI,PT,SS,ODI,BASDAI,BASFI,BASMI,BAS-G,BASRI and SF-36 between male and female patients.Results:The ratio of male/female was 1.6:1.Compared with male patients,female patients had an older mean age of disease onset,shorter mean time of disease duration,higher mean baseline ESR and CRP and a lower proportion of HLA-B27 positive(P<0.05).Additionally,women had higher ODI,BASAI and BASDRI score than men;however,women exhibited lower BASMI score(P<0.05).In sagittal spinopelvic parameters,women had higher GK and SVA(P<0.05).With respect to the domains of SF-36,women showed lower role emotional score and mental health score than men;whereas women had higher physical functioning score and social functioning score(P<0.05).Conclusion:In AS patients requiring surgical correction,the male/female ratio of 1.6:1 was observed.Compared with male AS patients,female patients had a higher burden of disease and a later disease onset of shorter duration.Moreover,notable limitations of physical functioning and social functioning were found in male AS patients.While obvious damages of role emotional and mental health were observed in females AS patients.
Keywords/Search Tags:ankylosing spondylitis, serum microRNAs, Solexa sequencing, biomarkers, aorta, closing-opening wedge osteotomy, CT, abdominal cavity, pedicle subtraction osteotomy, sex, quality of life, clinical feature
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