Corrigendum: Single-cell transcriptomics reveals the complexity of the tumor microenvironment of treatment-naive osteosarcoma.

[This corrects the article DOI: 10.3389/fonc.2021.709210.].

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma.

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

Upper and lower adjacent segment range of motion after fixation of different lumbar spine segments in the goat: an in vitro experiment.

OBJECTIVES: The purpose of this study was to examine the biomechanical effects of fixation on range of motion (ROM) in the upper and lower adjacent segments of different lumbar spine segments in a goat spine model. METHODS: Fifteen goat spine specimens (vertebrae T12-S1) were randomly divided into three groups: A (single-segment fixation), B (double-segment fixation), and C (triple-segment fixation). Motion in different directions was tested using a spinal motion simulation test system with five external loading forces. Transverse, forward-backward, and vertical displacement of the upper and lower adjacent segments were measured. RESULTS: As the external load increased, the upper and lower adjacent segment ROM increased. A significantly greater ROM in group C compared with group A was found when the applied external force was greater than 75 N. The upper adjacent segment showed a significantly greater ROM than the lower adjacent segment ROM within each group. CONCLUSIONS: Adjacent segment ROM increased with an increasing number of fixed lumbar segments. The upper adjacent segment ROM was greater than that of the lower adjacent segments. Adjacent segment stability after lumbar internal fixation worsened with an increasing number of fixed segments.

Treatment strategy of unstable atlas fracture: A retrospective study of 21 patients.

At present, the posterior cervical approach with open reduction and internal fixation (ORIF) remains a commonly effective treatment for unstable Atlas fracture. However, the inserted screws into the C1 lateral mass of some unstable atlas fracture are very difficult, so that the operation is forced to change into C0 to C2 fusion. In order to improve the successful rate of lateral mass screw placement, we introduced a method of fixing lateral mass with a towel clamp in posterior transpedicular fixation, and explore the efficacy and feasibility.Twenty-one consecutive patients with unstable atlas fracture were treated via this method from October 2012 to July 2017. All cases had neck pain and restricted motion of neck movement on admission. Electronic medical records and pre- and postoperative radiographs were reviewed. Screw and rod placement, bone fusion, and spinal cord integrity were assessed via long-term follow-up with anteroposterior and lateral radiographs and computed tomography. Follow-up included clinical assessment of neurological function, assessment of pain using the visual analog scale (VAS), and assessment of the activities of daily living using the neck disability index (NDI).The mean follow-up duration was 22.1 months (range: 12-54 months). No screw loosening or breakage, plate displacement, neurovascular injury, and severe complications occurred during follow-up. The mean operative time was 112.4 ±â€Š14.9 min (range: 82-135 min), and mean blood loss was 386.2 ±â€Š147.9 mL (range: 210-850 mL). One patient experienced continuous neck pain postoperatively, but this gradually disappeared with analgesic administration. At final follow-up, all patients had bone fusion, the VAS scores and NDI were significantly improved compared with preoperatively.Fixing the C1 lateral mass with a towel clamp during posterior transpedicular fixation for unstable atlas fracture appears to be a safe and reliable method, with the advantages of being a simple technique with few complications.

Association between ladybird homeobox 1 gene polymorphisms and adolescent idiopathic scoliosis: A MOOSE-compliant meta-analysis.

The Ladybird Homeobox 1 (LBX1) gene has been implicated in the etiology of adolescent idiopathic scoliosis (AIS). The association between LBX1 gene polymorphisms and AIS has been investigated in several studies. However, these findings have yield contradictory results rather than conclusive evidence.This study is to provide a meta-analysis of the published case-control studies on the association between LBX1 gene polymorphisms and AIS in Asian and Caucasian populations.This meta-analysis conformed to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We conducted a literature research on PubMed, Embase, Web of Science, and Cochrane Library until February 10, 2018. We included all case-control or cohort studies about association between LBX1 gene polymorphisms and AIS. The Risk Of Bias In Non-randomised Studies-of Interventions and Critical Appraisal Skills Programme were used to evaluate the risk of bias and study quality. We assessed the strength of association by pooled odds ratios (ORs) and 95% confidence intervals (CIs) in all genetic models under a fixed-effect model or random-effect model. We further performed subgroup analysis by ethnicity and sex. Sensitivity analysis and publication bias were also undertaken.A total of 10 studies (11,411 cases and 26,609 controls) were included in this meta-analysis. The pooled results showed a statistically significant association between LBX1 gene polymorphisms and AIS (for rs11190870, T vs C, OR = 1.54, 95% CI = 1.48-1.61, P < .00001; for rs625039, G vs A, OR = 1.50, 95% CI: 1.38-1.62; P < .00001; for rs678741, G vs A, OR = 0.74, 95% CI: 0.63-0.86; P < .0001; for rs11598564, G vs A, OR = 1.41, 95% CI: 1.31-1.51; P < .0001). For stratified analyses by ethnicity and sex, robust significant associations were detected in Asian and Caucasian populations, and in women and men under all genetic models.T allele of rs11190870 and G alleles of rs625039 and rs11598564 represent risk factors for AIS, but G allele of rs678741 may play a protective role in the occurrence of AIS. Further research is needed to confirm this finding and to understand its implications.

Giant cell tumors combined with secondary aneurysmal bone cysts are more likely to develop postoperative recurrence: A retrospective study of 256 cases.

PURPOSE: The epidemiology and clinicopathology of aneurysmal bone cysts (ABCs) secondary to giant cell tumors of bone (GCTBs) have been well documented in the previous literature. However, reports on whether secondary ABCs could affect the postoperative recurrence of GCTBs are rare. This study analyzed the effects of secondary ABCs and other relevant clinical factors on the postoperative recurrence of GCTBs of the extremities. METHODS: We retrospectively analyzed 256 cases of GCTBs of the extremities that were treated surgically at our institution. Among them, there were 60 patients diagnosed with GCTBs combined with secondary ABCs and 196 patients diagnosed with simple GCTBs. Intralesional curettage and tumor resection were performed in 136 and 120 cases, respectively. Univariate analysis, Kaplan-Meier survival analysis, and multivariate regression analysis were used to assess the factors for postoperative recurrence. The follow-up period was at least 24 months. RESULTS: The total postoperative recurrence rate was 32%. The recurrence rate in the secondary ABCs group was significantly higher than that in the simple GCTBs group (53.3% vs 25.5%, P < 0.05). Curettage was associated with a higher recurrence rate than tumor resection (42.5% vs 20%, P < 0.05). Kaplan-Meier survival analysis showed that patients with GCTBs combined with secondary ABCs and who were treated by intralesional curettage had a decreased disease-free survival rate. The hazard ratio was 2.18 (95% confidence interval [CI], 1.15-4.13) for the group of GCTB combined with ABCs ( P = 0.01) and 1.97 (95% CI, 1.22-7.50) for the curettage group ( P = 0.01), respectively. Multivariate regression analysis revealed that the presence of secondary ABCs and curettage were independent factors for recurrence of GCTBs. CONCLUSION: According to the results of this study, the presence of secondary ABCs is a potential risk factor for postoperative relapse of GCTBs.

Analysis of the clinical efficacy of tumor resection methods used in 20 patients with clavicular tumor.

BACKGROUND: To retrospectively analyze the tumor resection method used in 20 patients with clavicular tumors and evaluate its clinical efficacy. METHODS: A total of 9 patients with clavicular benign tumors underwent intracapsular resection, and 11 patients with clavicular malignant tumors underwent tumor resection from May 2012 to May 2017. Of the 11 patients, 5 underwent clavicular reconstruction using the plate-cement complex. Surgical efficacy was assessed using the Musculoskeletal Tumor Society, Constant-Murley, and American Shoulder and Elbow Surgeons shoulder outcome scores preoperatively until 12 months postoperatively. RESULTS: The average duration of follow-up care was 33.7 (12-71) months. Of the 20 patients, 3 patients died, 3 survived with tumor recurrence or metastasis, and 14 survived with no tumor recurrence. Among the 5 patients who underwent resection of malignant clavicular tumors and reconstruction, 2 underwent a re-operation because of a loose screw and plate displacement. In the functional assessment of the shoulder joint, patients with benign and malignant clavicular tumors showed significantly higher scores postoperatively compared with preoperative scores. For malignant clavicular tumors, no significant improvement was observed when comparing the non-reconstruction and reconstruction groups. CONCLUSIONS: Surgery is an optimal treatment for clavicular tumors. In patients with benign clavicular tumors, simple intracapsular resection can achieve a satisfactory prognosis. Reconstruction of a clavicular defect after resection of a clavicular malignant tumor is not recommended.

Vitamin D Receptor gene polymorphisms and plasma levels are associated with lumbar disc degeneration.

The purpose of this study was to investigate the association of Vitamin D Receptor (VDR) gene polymorphisms and VDR levels with lumbar disc degeneration (LDD). TaqMan SNP Genotyping Assay was utilized to probe VDR gene polymorphisms including the FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236) in 454 patients with LDD and 485 controls. Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect plasma VDR levels. The patients with LDD were divided into three subgroups (subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis; subgroup 3: lumbar spondylolisthesis) to further probe the association of plasma VDR levels and VDR gene polymorphisms and LDD. Moreover, immunohistochemistry (IHC) was implemented to evaluate VDR expression in lumbar degenerated disc and normal disc. Allele and genotype frequency of TaqI (rs731236) were significantly different in patients with LDD and controls (all P < 0.05). For TaqI polymorphism, the frequencies of T allele were significantly higher in the LDD patients compared with controls (OR = 1.319; 95%CI 1.091 to 1.595; P = 0.004, adjusted (OR = 1.319; 95%CI 1.091 to 1.595; P = 0.004, adjusted OR = 1.383; 95%CI 1.135 to 1.684; P = 0.016). Furthermore, the allele distribution showed a higher frequency of the T allele in the patients with lumbar disc herniation in subgroup 1 (OR = 1.384; 95% CI 1.105 to 1.732; P = 0.004, adjusted OR = 1.319; 95%CI 1.091 to 1.595; P = 0.016). Plasma VDR levels and VDR expression were significantly lower in patients with LDD compared with controls (all P < 0.05). Moreover, the TT genotype of TaqI polymorphism was significantly associated with lower plasma VDR levels in patients with LDD (P = 0.002). TaqI (rs731236) polymorphism was associated with a predisposition to LDD. Plasma VDR and VDR expression levels may be the marker for the occurrence and development of LDD.

Comparison of clinical outcomes and safety between laminectomy with instrumented fusion versus laminoplasty for the treatment of multilevel cervical spondylotic myelopathy.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: Posterior laminectomy with instrumented fusion and laminoplasty are widely used for the treatment of multilevel cervical spondylotic myelopathy (MCSM). There is great controversy over the preferred surgical method. The purpose of this study is to evaluate the clinical outcomes and safety between laminectomy with instrumented fusion and laminoplasty for the treatment of MCSM. METHODS: Related studies that compared the effectiveness of laminectomy with instrumented fusion and laminoplasty for the treatment of MCSM were acquired by a comprehensive search in PubMed, Embase, the Cochrane library, CNKI, VIP, and WANFANG up to April 2018. Included studies were evaluated according to eligibility criteria. The main endpoints included: preoperative and postoperative Japanese Orthopedic Association (JOA) scores, preoperative and postoperative visual analog scale (VAS), preoperative and postoperative cervical range of motion (ROM), preoperative and postoperative cervical curvature index (CCI), overall complication rate, C5 nerve palsy rate, axial symptoms rate, operation time and blood loss. RESULTS: A total of 15 studies were included in this meta-analysis. All of the selected studies were of high quality as indicated by the Newcastle-Ottawa scale (NOS). Among 1131 patients, 555 underwent laminectomy with instrumented fusion and 576 underwent laminoplasty. The results of this meta-analysis indicated no significant difference in preoperative and postoperative JOA scores, preoperative and postoperative VAS, preoperative and postoperative CCI, preoperative ROM and axial symptoms rate. However, compared with laminoplasty, laminectomy with instrumented fusion exhibited a higher overall complication rate [RR = 1.99, 95% confidence intervals (CI) (1.24, 3.21), P <.05], a higher C5 palsy rate [RR = 2.22, 95% CI (1.30, 3.80), P <.05], a decreased postoperative ROM [SMD = -1.51, 95% CI (-2.14, -0.88), P <.05], a longer operation time [SMD = 0.51, 95% CI (0.12, 0.90), P <.05] and increased blood loss [SMD = 0.47, 95% CI (0.30, 0.65), P <.05]. CONCLUSION: These results suggested that both posterior laminectomy with instrumented fusion and laminoplasty were determined to be effective for MCSM. However, laminoplasty appeared to allow for a greater ROM, lower overall complication and C5 palsy rates, shorter operation time and lower blood loss. Future well-designed, randomized controlled trials are still needed to further confirm our results.

Intraoperative rupture of tuberculous pseudoaneurysm associated with spinal tuberculosis: A case report and literature review.

INTRODUCTION: The increase in the incidence of tuberculosis in developing countries has resulted in increased reporting on more related complications. We report the successful management of an intraoperative spontaneous rupture of a tuberculous pseudo aneurysm associated with spinal tuberculosis. METHODOLOGY: We report the case of a 66 years old woman diagnosed with spinal tuberculosis of the T3/T4 vertebrae. During an anterior approach surgical reconstruction for the degenerative vertebrae, massive hemorrhage was observed after the removal of a portion of the prevertebral fascia of the affected vertebrae. This led to the exploration of the hilar fascia for the possibility of hilar hemorrhage, and when no hemorrhage was observed, aneurysm rupture was suspected. A portion of the hilar fascia was then sutured to the prevertebral fascia and the hemorrhage was partially controlled. RESULTS: On the 32nd month post-operative follow-up, the symptoms of chest and back pain had disappeared and the tuberculous lesion eradicated. CONCLUSION: Presently, there are few reports on the successful treatment of intraoperative spontaneous rupture of tuberculous pseudoaneurysms. We therefore report on the successful management of such a case.

Comparison of anchor screw fixation versus mini-plate fixation in unilateral expansive open-door laminoplasty for the treatment of multi-level cervical spondylotic myelopathy.

STUDY DESIGN: Systematic review and meta-analysis. BACKGROUND: Anchor screw fixation and mini-plate fixation are widely used in unilateral open-door laminoplasty. There is a great controversy over the preferred fixation method. The purpose of this study is to evaluate the clinical outcomes between anchor screw fixation and mini-plate fixation for the treatment of multilevel cervical spondylotic myelopathy (MCSM). METHODS: Related studies that compared the clinical effectiveness of anchor screw fixation and mini-plate fixation in cervical laminoplasty for the treatment of MCSM were acquired by a comprehensive search in PubMed, Embase, the Cochrane library, CNKI, VIP, and WANFANG up to March, 2018. Included studies were evaluated according to eligibility criteria. The main end points included: preoperative Japanese Orthopedic Association (JOA) scores, postoperative JOA scores, JOA scores improvement rate, preoperative and postoperative cervical range of motion (ROM), preoperative and postoperative cervical curvature index (CCI), lamina open angle, operation time, blood loss, C5 nerve palsy rate and axial symptoms rate. RESULTS: Papers in English and Chinese were searched for the initial review, but only 12 articles in Chinese were included in this meta-analysis. All of the selected studies were of high quality as indicated by the Newcastle-Ottawa scale (NOS). Among 809 patients, 372 underwent anchor screw fixation and 437 underwent mini-plate fixation. The results of this meta-analysis indicated that no significant difference was found in preoperative JOA score, JOA scores improvement rate, preoperative CCI, preoperative ROM, C5 palsy rate and blood loss. However, compared with mini-plate fixation, anchor screw fixation patients showed higher axial symptoms rate [RR = 1.75, 95% CI (1.31, 2.35), P <.05], lower postoperative JOA scores [SMD = -0.38, 95% CI (-0.62, -0.15), P <.05], lower postoperative CCI [SMD = -0.64, 95% CI (-0.94, -0.33), P <.05], lower postoperative ROM [SMD = -1.11, 95% CI (-2.18, -0.04), P <.05], smaller lamina open angle [SMD = -1.98, 95% CI (-3.71, -0.24), P <.05], shorter operation time [SMD = -0.33, 95% CI (-0.59, -0.07), P <.05]. CONCLUSIONS: Compared with anchor screw fixation, mini-plate fixation in cervical laminoplasty appears to achieve better clinical and radiographic outcomes with fewer surgical complications. However, future well-designed, randomized controlled trials are still needed to further confirm our results.

Residual bone fragments in tibiofibular joint and postoperative local recurrence: an analysis of 21 cases of proximal fibular giant cell tumour.

BACKGROUND: Currently, there are no known reports on the aetiology of local giant cell tumour (GCT) recurrence in the proximal fibula following en bloc resection. We analysed 21 cases of proximal fibular GCT, focusing on the presence of residual bone in the tibiofibular joint, its causes and its impact on postoperative recurrence. METHODS: We retrospectively analysed 21 cases with proximal fibular GCT occurring between 2000 and 2017. RESULTS: There were 14 males and 7 females. The average patient age was 25.0 years. Seventeen patients were diagnosed and treated at our facility, while 4 were referred after local recurrence. Six patients presented with residual bone fragments in the tibiofibular joint during their first month of follow-up. Patients with residual bone fragments had a higher local recurrence rate (83.3%) than those without (0%, p = 0.0003). Upon further analysis, patients with a preoperative Campanacci grade III tumour (p = 0.0055) and pathological fractures (p = 0.0109) were at a higher risk of exhibiting postoperative residual bone fragments. CONCLUSIONS: The presence of residual bone fragments in the tibiofibular joint was the main cause of postoperative local recurrence. The presence of residual bone fragments may be related to the preoperative Campanacci grade and pathological fractures. Therefore, close attention should be paid to postoperative follow-up examinations, and if recurrence is suspected, surgical resection should be planned.

Collagen IX gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis.

BACKGROUND: An increasing number of studies have investigated associations between collagen IX alpha 2 chain (COL9A2) and collagen IX alpha 3 chain (COL9A3) gene polymorphisms and the risk of lumbar disc degeneration (LDD). However, these studies have yielded contradictory results. The purpose of this meta-analysis is to investigate the association between the collagen IX gene polymorphisms (rs12077871, rs12722877, rs7533552 in COL9A2; rs61734651 in COL9A3) and LDD. METHODS: All relevant articles were collected from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). The last electronic search was performed on September 1, 2017. The allele/genotype frequencies were extracted from each study. The odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of associations under the five comparison genetic models. Statistical analysis was performed by Review Manager (RevMan) 5.31 software. RESULTS: The meta-analysis of 10 case-control studies, including 2102 LDD cases and 2507 controls, indicated that COL9A2 gene (rs12077871, rs12722877, rs7533552) and COL9A3 gene (rs61734651) polymorphisms were not associated with LDD (rs12077871: T vs. C, OR = 1.85, 95% CI = 0.87-3.91, P = 0.11; rs12722877: G vs. C, OR = 0.83, 95% CI = 0.69-1.01, P = 0.06; rs7533552: G vs. A, OR = 1.11, 95% CI = 0.98-1.25, P = 0.09; rs61734651: T vs. C, OR = 1.57, 95% CI = 0.51-4.84, P = 0.43). The Egger text and the Begg funnel plot did not show any evidence of publication bias. CONCLUSION: rs12077871, rs12722877, and rs7533552 variants in COL9A2 and rs61734651 variant in COL9A3 were not significantly associated with a predisposition to LDD. Large-scale and well-designed studies are needed to confirm this conclusion.

Association between COL11A1 (rs1337185) and ADAMTS5 (rs162509) gene polymorphisms and lumbar spine pathologies in Chinese Han population: an observational study.

OBJECTIVES: A previous study identified a significant association between several single nucleotide polymorphisms (SNPs) and lumbar disc degeneration (LDD) in Indians. To validate the association between these SNPs and specific lumbar spine pathologies, we performed a case-control study in Chinese Han population. DESIGN: An observational study. SETTING: University Hospital in Nanning, China. PARTICIPANTS: This study included 428 patients with LDD and 400 normal controls. OUTCOME MEASURES: Patients with LDD were classified into four subgroups, including disc herniation only (subgroup 1), discopathies or/and osteochondrosis associated with disc herniation (subgroup 2), spinal stenosis or/and spondylolisthesis (subgroup 3) and degenerative scoliosis (subgroup 4). This study was conducted by examining two aspects: environmental factors and SNP genotyping. The environmental factors were evaluated with a questionnaire survey including questions about body mass index, smoking habits, the physical demands of their job and exposure to vibrations. Rs1337185, rs5275, rs5277, rs7575934, rs3213718 and rs162509 were genotyped using a PCR-based invader assay. RESULTS: The physical workload was significantly higher in patients with lumbar spine pathologies than in the normal controls (p=0.035). The genotype and allele frequencies of rs1337185 and rs162509 were significantly different between the patients with LDD and the normal controls. In rs1337185, a significant association was found between the C allele (risk allele) and the presence of disc herniation (OR=1.80; 95% CI 1.21 to 2.68; p=0.003, adjusted p=0.012) and the presence of spinal stenosis and spondylolisthesis (OR=1.92; 95% CI 1.29 to 2.89; p=0.001, adjusted p=0.004). In rs162509, the G allele represented 1.58-fold increased risk to suffer from disc herniation (OR=1.58; 95% CI 1.20 to 2.09; p=0.001, adjusted p=0.004). CONCLUSION: The SNPs rs1337185 in COL11A1 and rs162509 in ADAMTS5 are associated with susceptibility to LDD. The C allele of rs1337185 is risky for patients who are affected by lumbar pathologies such as disc herniation, stenosis and spondylolisthesis. The G allele of rs16250 represents a risk factor for the development of disc herniation.

Vitamin D receptor gene polymorphisms and lumbar disc degeneration: a systematic review and meta-analysis.

PURPOSE: To examine the association between Vitamin D receptor (VDR) gene polymorphisms and lumbar disc degeneration (LDD) predisposition. METHODS: A comprehensive literature search was conducted to identify all the relevant studies. The allele/genotype frequencies were extracted from each study. We calculated the pooled odds ratios (ORs) and 95 % confidence intervals (CI) to assess the strength of the association between the VDR gene polymorphisms and LDD risk. Statistical analysis was performed using RevMan 5.31 software. RESULTS: A total of 23 case-control studies (1835 cases and 1923 controls) were included in this systematic review. For the TaqI (rs731236), FokI (rs2228570) and ApaI (rs7975232) polymorphisms of VDR gene, nine studies, seven studies, and five studies, were eventually included in the meta-analysis, respectively. There was no evidence that the VDR gene polymorphisms (TaqI, FokI, ApaI) had significant associations with LDD risk.(for TaqI allelic comparison, OR = 1.07, 95 % CI 0.81-1.40, p = 0.64; for FokI allelic comparison, OR = 1.23, 95 % CI 0.83-1.82, p = 0.31; for ApaI allelic comparison, OR = 0.79, 95 % CI 0.55-1.14, p = 0.20). For stratified analyses by ethnicity and study design, no significant associations were found in Caucasian population and Asian population, as well as the population-based studies and hospital-based studies under all genetic models. CONCLUSIONS: TaqI, FokI, and ApaI polymorphisms of VDR gene were not significantly associated with the predisposition of LDD. Large-scale and well-designed international studies are needed to further analyze this field.

Assessing the evolution of scientific publications in orthopedics journals from mainland China, Hong Kong, and Taiwan: a 12-year survey of the literature.

BACKGROUND: In China, the field of orthopedics has experienced significant growth over the past 12 years. However, the recent status of research on orthopedics among individuals in mainland China, Hong Kong, and Taiwan is unknown. In this study, we investigated characteristics and trends of orthopedics publications from these three regions. METHODS: Between 2003 and 2014, all articles published in 63 orthopedics journals originating from mainland China, Hong Kong, and Taiwan were identified via Science Citation Index Expanded (SCIE) database. A survey was conducted to systematically analyze the published orthopedics articles from the three regions according to the numbers of articles, study design, impact factors (IFs), citations, most prolific authors, and institutions. Additionally, we evaluated global trends in orthopedics publications, and ranked top 10 countries in terms of the total number of published articles over 12 years and the number of published articles per year. RESULTS: A total number of 123,317 articles were published in the 63 orthopedics journals between 2003 and 2014. The worldwide number of annually published orthopedics articles tended to increase during the study period. The total number of orthopedics publications from the three regions, especially in mainland China, increased markedly from 2003 to 2014. The annual number of orthopedics articles from mainland China increased from 6 in 2003 to 813 in 2014, Hong Kong increased from 32 in 2003 to 71 in 2014, and Taiwan increased from 68 in 2003 to 168 in 2014. For accumulated IFs and total citations of articles, mainland China ranked the first place, followed by Taiwan and Hong Kong. However, publications from Taiwan had the highest average citations per article, and publications from Hong Kong had the highest average IFs. Among the top 10 most prolific authors and institutions, 4 authors and 4 institutions were from Taiwan, 3 authors and 4 institutions were from mainland China, and 3 authors and 2 institutions were from Hong Kong. CONCLUSIONS: The quantity of articles published in international orthopedics journals from mainland China presented a remarkable upward trend during the past 12 years. Given the relative size of the populations, it should be emphasized that mainland China still has a long way to go to achieve the academic performance of Hong Kong and Taiwan.

[Ischemic neurological injury during spinal deformity surgery: current status].

Ischemic neurological injury is the most feared complication of spinal deformity surgery.In recent years, more attention has been paid to ischemic neurological injury during spinal deformity surgery including causes, risk factors, and prevention. The direct and indirect causes of ischemic neurological injury contains ligature of the segmental arteries, perioperative bleeding and excessive stretching or shortening of the spinal cord.Those patients at greatest risk for paraplegia following diagnosis of thoracic kyphosis or kyphoscoliosis, unilateral vessel ligation, perioperative hypotension, and extensive anterior and posterior surgery. Keeping reasonable mean arterial pressure and multimodal intraoperative monitoring may effectively prevent ischemic neurologic injury during surgery for spinal deformity.

Formononetin induces apoptosis of human osteosarcoma cell line U2OS by regulating the expression of Bcl-2, Bax and MiR-375 in vitro and in vivo.

BACKGROUND/AIMS: Phytoestrogens are known to prevent tumor progression by inhibiting proliferation and inducing apoptosis in cancer cells. Formononetin is one of the main components of red clover plants, and is considered as a typical phytoestrogen. This study investigates formononetin induction of apoptosis of human osteosarcoma cell line U2OS by regulating Bcl-2 and Bax expression in vitro and in vivo. METHODS: U2OS cells were treated with different concentrations of formononetin and the proliferation of the cells was measured using an MTT assay. Cell apoptosis was examined by flow cytometry. The levels of miR-375, Bax and Bcl-2 protein expression in treated cells were determined by Western blot and RT-PCR. The antitumor activity of formononetin was also evaluated in vivo in nude mice bearing orthotopic tumor implants. RESULTS: High concentrations of formononetin significantly suppress the proliferation of U2OS cells and induce cell apoptosis. Moreover, compared to control group the expression of Bcl-2 and miR-375 decreases with formononetin in the U2OS cells, while Bax increases. CONCLUSION: Formononetin has inhibitory effects on the proliferation of U2SO cells, both in vitro and in vivo. This antitumor effect is directly correlated with formononetin concentration.

Occipito-cervical fusion following gross total resection for the treatment of spinal extramedullary tumors in craniocervical junction: a retrospective case series.

BACKGROUND: Previous studies found that the facet joint of the C1 vertebra were removed (C1 facetectomy) before extirpation from the extramedullary tumor in craniocervical junction, leading to postoperative upper cervical instability or deformity. Occipito-cervical fusion (OCF) is a demanding and morbid surgical procedure, which can be used in such patients. This study is to analyze the clinical manifestation and surgical outcome of patients with craniocervical extramedullary tumor undergoing an extirpation of spinal tumors and OCF by one-stage posterior approach. METHODS: The surgical and clinical databases were searched for operative procedures that had been performed for patients with spinal extramedullary tumors in craniocervical junction at a single institution from January 2008 to July 2011. The following inclusion criteria were applied: (1) initial surgery for craniocervical extramedullary tumor, (2) gross total resection and occipito-cervical fusion had been performed, (3) minimum 2-year follow-up, and (4) no previous cervical spine surgery. Medical records included demographic characteristics, clinical assessment, and radiographic studies. Clinical outcomes before and after the surgery were assessed using Frankel grade and the Japanese Orthopaedic Association (JOA) score. Cervical sagittal alignment was evaluated by C0-2 angle and C2-7 angle based on X-ray. RESULTS: Nine patients were included in the study. Five patients had schwannoma, three patients had meningioma, and only one patient had neurofibroma. All cases were followed up for 24-42 months (average, 34.2 months). At the last follow-up, three patients improved from Frankel grade C to grade D, two patients from Frankel grade C to grade E, and one patient from Frankel grade D to grade E, while two patients remained stationary at the Frankel grade D. The JOA score of the eight patients were 9.0 (range, 6-17) before surgery and were 14.6 (range, 12-17) at the most recent follow-up (p < 0.05). The mean C0-2 angle and the mean C2-7 angle before surgery were 26.2 ± 5.3° and 17.4 ± 13.1°, respectively. At the end of follow-up, the mean C0-2 angle was 25.6 ± 4.8°, and the mean C2-7 angle decreased to 12.7 ± 10.9°. However, this trend did not reach statistical significance (p < 0.05). Two patients suffered from cerebrospinal fluid leaks postoperatively. All patients had a satisfactory fusion and did not exhibit a tumor recurrence during the follow-up period. CONCLUSIONS: OCF following gross total resection appears to be a useful surgical procedure for the craniocervical extramedullary tumors requiring C1 facetectomy and does not cause postoperative kyphosis of the upper cervical spine.

Phenethyl isothiocyanate enhances adriamycin­induced apoptosis in osteosarcoma cells.

Adriamycin (ADM) is a first­line agent administered during the therapeutic regimes against osteosarcoma. Clinical administration of ADM produces systemic toxicity and resistance in patients, which restricts its applicability. In the present study the effects of phenethyl isothiocyanate (PEITC) on ADM­induced apoptosis in osteosarcoma cells was evaluated. Using U2­OS osteosarcoma cell line cells, treatment with PEITC or ADM for 24 h was observed to dose­dependently inhibit proliferation of U2­OS cells with half maximal inhibitory concentration (IC50) values of 5.33 µM and 10.32 µg/ml, respectively. When U2­OS cells were treated with a combination of the two agents, the inhibition was apparently enhanced, as the IC50 values decreased to 2 µM for PEITC and 1 µg/ml for ADM. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed that treatment with PEITC or ADM alone reduced the viability of the U2­OS cells. Furthermore, the viability of the U2­OS cells was additionally reduced when treatment was with PEITC and ADM together. Supporting this finding, the activity and expression of caspase­3 were observed to be enhanced in the U2­OS cells following treatment with either PEITC or ADM, or a combination of the two. These results clearly indicate that PEITC enhances ADM­induced apoptosis in osteosarcoma cells.