Down-regulation of microRNA152 is associated with the diagnosis and prognosis of patients with osteosarcoma.

Potential values of microRNA152 (miR-152) as a serum diagnostic and prognostic biomarker have not been determined in human osteosarcoma. By detecting the expression of miR-152 among 80 osteosarcoma patients, 20 periostitis patients and 20 healthy individuals using qRT-PCR, we aimed to explore the clinical significance of miR-152 in osteosarcoma patients. The expression of miR-152 was significantly decreased in patients with osteosarcoma compared to patients with periostitis (P<0.01) and healthy controls (P<0.01). The relationship between clinicopathologic characteristics and miR-152 was analyzed by chi-square test. The outcome indicated that miR-152 might be linked with the development of osteosarcoma. Moreover, the receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of miR-152. The result demonstrated that miR-152 might be a promising diagnostic marker of osteosarcoma with an AUC of 0.956, combing with 92.5% specificity and 96.2% sensitivity. The relationship between miR-152 and overall survival of osteosarcoma patients was analyzed by Kaplan-Meier curve and log rank test. As a result, the survival time of patients with low miR-152 expression was significantly shorter than those with high miR-152 expression (P<0.001). Then Cox regression analysis was used to estimate the prognostic value of miR-152 in osteosarcoma. The outcomes showed that low miR-152 expression (P=0.004) might be a potential independent prognostic marker for osteosarcoma patients. These findings suggested that down-regulation of miR-152 could be considered as a predictor for diagnosis and prognosis of osteosarcoma patients.

Association between CTLA-4 gene polymorphism and ankylosing spondylitis: a case-control study.

AIMS: The aim of our study was to evaluate the association between CTLA-4 polymorphisms (+49A/G, -318C/T and CT60A/G) and ankylosing spondylitis (AS) susceptibility. METHODS: A total of 120 AS cases and healthy controls, matched on the age and gender, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) were used to determine the gentypes of +49A/G, -318C/T and CT60A/G polymorphisms. Genotype distribution in control group was assessed by Hardy Weinberg Equilibrium (HWE) test. Odds ratio (OR) with 95% confidence interval (95% CI) were adopted to evaluate the relationship of CTLA-4 polymorphisms and AS susceptibility. RESULTS: In our study, genotype distribution of the three polymorphisms in control group was consistent with the HWE (P > 0.05). The genotype analysis showed that AA genotype of + 49A/G polymorphism could increase the risk for AS (OR=2.357, 95% CI=1.127-4.930). Moreover, the frequency of A allele was also presented as a risk factor for AS. Additionally, AA genotype and A allele of CT60A/G appeared to be related with AS susceptibility (OR=2.610, 95% CI=1.047-6.510; OR=1.751, 95% CI=1.160-2.641). However, the T allele of -318C/T appeared to be a protective factor for AS (OR=0.383, 95% CI=0.228-0.643). CONCLUSION: In summary, there existed significant association between CTLA-4 gene polymorphisms and increased or decreased risk for AS.

TNF-α and IL10 polymorphisms interaction increases the risk of ankylosing spondylitis in Chinese Han population.

AIMS: The target of this article was to reveal the role of tumor necrosis factors α (TNF-α) and Interleukin-10 (IL10) gene polymorphisms in ankylosing spondylitis (AS) development and explore the interaction between these two gene polymorphisms. METHODS: The genotyping of gene polymorphims was conducted using ABI Taqman assay method in 84 AS patients and 92 healthy people. Hardy-Weinberg equilibrium (HWE) was checked in the control group and the genotypes and alleles difference were compared with χ(2) test. Odds ratio (OR) with 95% confidence interval (CI) was calculated to identify the strength of association between gene polymorphism and disease. Meanwhile, multifactor dimensionality reduction (MDR) method was used to analysis the interaction between gene polymorphisms. RESULTS: The genotypes CG+CC of the minor allele in IL10 rs1878672 in cases was obviously higher frequency than the controls (P=0.03) and the minor allele C was also associated with the increased risk of AS, compared with G allele (OR=2.05, 95% CI=1.08-3.89). Rs3024490 in IL10 also showed a significant correlation to the onset risk of AS (GG vs. TT: OR=3.03, 95% CI=1.04-8.87; G vs. T: OR=1.70, 95% CI=1.08-2.68). What's more, there was the interaction between TNF-α rs3093662 and IL10 rs3021094, rs3024490 polymorphisms in AS. CONCLUSIONS: IL10 rs1878672 and rs3024490 polymorphisms obviously increase the susceptibility to AS, but not TNF-α rs3093662. Both IL10 and TNF-α polymorphisms may affect the onset of AS.

Genetic analysis of TNFST15 variants in ankylosing spondylitis.

AIMS: The purpose of this study was to explore the role of TNF-like ligand 1A (TL1A) gene (TNFST15) polymorphisms (rs3810936, rs7848647, and rs6478109) in the generation of ankylosing spondylitis (AS). METHODS: Polymerase chain reaction (PCR) and sequencing were used to conduct the genotyping of TNFSF15 polymorphisms in 113 AS patients and 120 healthy persons as the case and control groups. The frequencies comparison was performed by chi-square or t test between the two groups. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to represent the correlation between TNFSF15 polymorphism and AS. Besides, genotypes distribution of the former in controls was checked by Hardy-Weinberg equilibrium (HWE). RESULTS: There was statistically significant difference in AS patients and controls based on family history. Among TNFSF15 polymorphisms, only TT genotype frequency of rs3810936 in cases was obviously high, compared with the controls (P=0.04), the results indicated that TT was a high-risk genotype (OR=2.31, 95% CI=1.03-5.20). However, both of rs6478109, rs7848647 polymorphisms didn't show any association with AS. CONCLUSION: Rs3810936 of TNFSF15 were related to the risk of AS and we should pay more attention to the role of TNFSF15 polymorphisms in the pathogenesis of AS in the future.

[Association study of WNT3A gene polymorphisms with the susceptibility to congenital scoliosis in a Chinese Han population].

OBJECTIVE: To investigate whether the polymorphisms of WNT3A gene are associated with congenital scoliosis (CS) and its various clinical phenotypes in a Chinese Han population. METHODS: A total of 127 CS patients admitted into PUMC were enrolled into this case-control study between October 2005 and September 2007. There were 55 boys and 72 girls with a mean age of 12.90 years old. Another 127 scoliosis-free control subjects at the same hospital during the same study period were frequency-matched with regards to age (± 3 years) and gender. Genomic DNA was extracted by QIAamp DNA Blood Mini Kit from peripheral blood leukocytes of each subject who had signed informed consent. Based on the genotypic data from the International HapMap project, the main functional single nucleotide polymorphisms (SNPs) were initially selected. The patients in the case group were classified into different clinical phenotypes according to vertebral defect type, location of deformity, extent of developmental disruption, combined rib malformations and neural canal deformity. The genotying of all selected SNPs was performed by SNPstream technology (Beckman Coulter SNPstream). All data of SNPs with polymorphism were processed by the association analysis based on a single SNP and between phenotypes and SNPs. And the pairwise linkage disequilibrium was calculated in the control population by Haploview 4.1 software. RESULTS: The SNP1 (rs964941) and SNP2 (rs752107) of WNT3A were genotyped. There was no linkage disequilibrium between two SNPs. No association was observed between SNP1 and SNP2 genotypes or allele polymorphisms and risk of CS and various clinical phenotypes (P > 0.05). CONCLUSIONS: The genetic variants of WNT3A gene may not be associated with the susceptibility to CS and various clinical phenotypes of CS in Chinese Han population.

[Clinical results of posterolateral fusion in treating lumbar low-grade spondylolisthesis].

OBJECTIVE: To analyze the clinical outcomes and losses of correction for posterolateral fusion on low-grade lumbar spondylolisthesis. METHODS: From October 2001 to July 2008, 37 patients with a mean age of 60.1 years (range, 27 - 88 years) with low-grade lumbar spondylolisthesis treated with posterolateral fusion, including 9 males and 28 females, were reviewed retrospectively. The clinical outcomes were evaluated using the visual analogue scale (VAS) and Oswestry disability index (ODI). The fusion status and loss of correction were assessed using plain radiographs and CT. RESULTS: All the 37 patients had got complete follow-up for 14 - 96 months (average 36.4 months); post-operative reduction rate was 76.4%, and 34 patients (91.9%) showed loss of correction with a mean loss rate 5.8% (range, -3.0% - 25.8%). The percentage of slip of pre-operative, post-operative and final follow-up indicated significant difference (P < 0.05)compared with each other; post-operative intervertebral disc height indicated significant difference in comparison with that of pre-operatively and at final follow-up (P < 0.05); lumbar lordosis angle at final follow-up showed significant difference when compared with that of pre-operatively and postoperatively (P < 0.05); VAS and ODI at final follow-up indicated significant difference in contrast to that of pre-operative (P < 0.05). Upon final follow-up, the complications were found in 2 cases who presented degenerative scoliosis at 15 and 17 months after the surgery, in 1 case with cranial adjacent segment retrolisthesis at the 14 months after the surgery, in 1 case with cut-out and breakage of screws at the 24 months after the surgery, and in 1 case with postoperative infection which were cured after debridement. CONCLUSIONS: For mid-term follow-up of low-grade lumbar spondylolisthesis, posterolateral fusion shows loss of correction in most cases, but presents good clinical outcome and fusion rate.

[Radiological evaluation of intervertebral angles on short-segment fusion of degenerative lumbar scoliosis].

OBJECTIVE: To analyze the radiological change of intervertebral angles after the short-segment fusion of degenerative lumbar scoliosis. METHODS: From January 2001 to May 2007, 28 patients (mean age 62 years old) with degenerative lumbar scoliosis, including 6 male and 22 female, were reviewed retrospectively. The average vertebra number in the lumbar curve were 4.8, ranging from 3 to 6. All the patients underwent posterior decompressive laminotomy, pedicle screw fixation, and posterolateral fusion. The fusion levels were within the curve in all the cases (mean 3.3 vertebrae), without exceeding the end vertebrae. All the patients took standing lumbar antero-posterior and sagittal radiological images pre and post-surgery and upon follow up. The coronal scoliosis Cobb angle, anterior and sagittal intervertebral angles of upper adjacent segment of proximal fused vertebra were measured. The following aspects were also evaluated such as bone graft fusion and complications. RESULTS: Follow up period of 25-97 months, average 50 months; post-operative scoliosis Cobb angle average correction rate was 33.7%, final follow up average correction loss was 3.7 degrees , pre-operative and final follow up results compared with post-operative indicated significant difference (P < 0.05); final follow-up antero-posterior proximal upper fusion segment intervertebral angle compared with pre-operative and postoperative presenting significant difference (P < 0.05). Upon final follow up, all cases did not present pseudo-arthrosis or internal instrumentation related complications. CONCLUSION: For degenerative lumbar scoliosis, short-segment fusion can produce limited correction on antero-posterior proximal upper fusion segment intervertebral angle and cannot stop its aggravation.

[Association study of SIM2 gene polymorphisms with susceptibility to congenital scoliosis in a Chinese Han population].

OBJECTIVE: To investigate whether polymorphisms of SIM2 gene are associated with congenital scoliosis (CS) in a Chinese Han population. and explore the relationship of between polymorphisms of SIM2 and clinical phenotypes of CS. METHODS: A case-control design was employed in this study. A total of 127 patients (55 boys, 72 girls, mean age 12.90 y/o) diagnosed with CS admitted at Peking Union Medical College (PUMC) Hospital were enrolled between October 2005 and September 2007. The scoliosis-free control subjects (127 cases) at the same hospital during the same study period were frequency-matched to the cases on age (+/- 3 years) and gender. Genomic DNA was extracted by QIAamp DNA Blood Mini Kit from peripheral blood leukocytes of each subject who had signed informed consent. Based on genotype data from the International HapMap project, the main functional single nucleotide polymorphisms (SNPs) initially were selected. Case group were classified into different clinical phenotypes according to vertebral defect type, location of deformity, extent of developmental disruption, combined rib malformations and neural canal deformity. Genotying of all selected SNPs was done by SNPstream technology (Beckman Coulter SNPstream). All the data of SNPs with polymorphism were analyzed by association analysis based on a single SNP, the association analysis between phenotypes and SNPs. And pairwise linkage disequilibrium was calculated in the control population using Haploview 4.1 software. RESULTS: SNP1 (rs2073601), SNP2 (rs2073417) and SNP3 (rs2051397) of SIM2 are genotyped. SNP2 and SNP3 in linkage disequilibrium. No association (P > 0.05) is observed between SNP1, SNP2 and SNP3genotypes/allele polymorphisms and risk of CS and different clinical phenotypes. CONCLUSION: Genetic variants of SIM2 gene may not be associated with the susceptibility to CS and different clinical phenotypes of CS in Chinese Han population.

[Assessment of curve flexibility in adolescent idiopathic scoliosis before operation].

OBJECTIVE: To compare the effects in assessing the curve flexibility of the adolescent idiopathic scoliosis (AIS) and predicting the outcomes of operation among different radiological techniques: supine lateral bending (SB), traction (Tr), and fulcrum bending radiographs. METHODS: 68 consecutive AIS patients, all with the single-curve types Ia/Ib/Ic according to the PUMC classification, divided into 4 groups according to the magnitude of Cobb's angle: moderate thoracic curve (n = 19, 40 degrees < Cobb's angle < or = 60 degrees ), severe thoracic curve (n = 13, Cobb's angle > 60 degrees ), moderate lumbar curve (n = 28, 35 degrees < Cobb's angle < or = 60 degrees ), and severe lumbar curve(n = 8, Cobb's angle > 60 degrees ) who were treated surgically underwent preoperative radiological evaluation including standing anteroposterior and lateral Tr, SB, and fulcrum bending radiographs. COBB angle was measured and the flexibility ratio was determined on each radiograph. The amounts of correction obtained by all radiographic methods were compared with the amount of surgical correction. RESULTS: The post-operative Cobb's angle of the moderate thoracic curve group was 9 degrees , not significantly different from that by fulcrum bending radiograph (P = 0.076), but significantly different from those by the other methods (both P < 0.01). The post-operative COBB angle of the severe thoracic curve group was 40 degrees , significantly different from all the radiographs before operation (all P < 0.01). The post-operative Cobb's angle of the moderate lumbar curve group was 4 degrees , significantly different from those by fulcrum bending and Tr radiographs (both P < 0.01) and that by SB (P = 0.013). The post-operative Cobb's angle of the severe lumbar curve group was 24 degrees , significantly different from those of anteroposterior and Tr radiograph (both P < 0.01) and those of fulcrum-bending and SB radiographs (P = 0.021 and P = 0.011). In the moderate thoracic curve group the operation correction rate was not significantly different from the flexibility rate by fulcrum-bending radiograph (P = 0.111), and was significantly different from the flexibility rates by SB and Tr radiographs (P = 0.011 and P = 0.000). In the severe thoracic curve group the operation correction rate was significantly different from the flexibility rates by different kinds of radiograph (all P = 0.111). In the moderate lumbar curve group the operation correction rate was significantly different from the flexibility rates by different kinds of radiograph (P < 0.111 or P = 0.019). In the severe lumbar curve group the operation correction rate was significantly different from the flexibility rates by different kinds of radiograph (P < 0.01 or P = 0.017). CONCLUSION: Fulcrum-bending radiography can better assess the flexibility and correction rate of thoracic curves in AIS, however, it can only predict those in moderate thoracic curves. Fulcrum-bending radiograph and SB radiograph are similar in predicting the flexibility in lumbar curves.