Farnesoid X receptor agonist attenuates subchondral bone osteoclast fusion and osteochondral pathologies of osteoarthritis via suppressing JNK1/2/NFATc1 pathway.

Osteoarthritis (OA) is a prevalent degenerative disease of the joint, featured by articular cartilage destruction and subchondral bone marrow lesions. Articular cartilage and subchondral bone constitute an osteochondral unit that guarantees joint homeostasis. During OA initiation, activated osteoclasts in subchondral bone ultimately result in impaired capacities of the subchondral bone in response to mechanical stress, followed by the degradation of overlying articular cartilage. Thus, targeting osteoclasts could be a potential therapeutic option for treating OA. Here, we observed that farnesoid X receptor (FXR) expression and osteoclast fusion and activity in subchondral bone were concomitantly changed during early-stage OA in the OA mouse model established by anterior cruciate ligament transection (ACLT). Then, we explored the therapeutic effects of FXR agonist GW4064 on the osteochondral pathologies in ACLT mice. We showed that GW4064 obviously ameliorated subchondral bone deterioration, associated with reduction in tartrate-resistant acid phosphatase (TRAP) positive multinuclear osteoclast number, as well as articular cartilage degradation, which were blocked by the treatment with FXR antagonist Guggulsterone. Mechanistically, GW4064 impeded osteoclastogenesis through inhibiting subchondral bone osteoclast fusion via suppressing c-Jun N-terminal kinase (JNK) 1/2/nuclear factor of activated T-cells 1 (NFATc1) pathway. Taken together, our results present evidence for the protective effects of GW4064 against OA by blunting osteoclast-mediated aberrant subchondral bone loss and subsequent cartilage deterioration. Therefore, GW4064 demonstrates the potential as an alternative therapeutic option against OA for further drug development.

Multisegment transforaminal lumbar interbody fusion (TLIF) combined with Ponte osteotomy in degenerative lumbar scoliosis (DLS) surgery: a minimum of five years' follow-up.

PURPOSE: To evaluate the long-term clinical outcomes of degenerative lumbar scoliosis (DLS) with the administration of multisegment transforaminal lumbar interbody fusion (TLIF) combined with Ponte osteotomy long-level fixation fusion, as well as to identify the factors affecting health-related quality of life (HRQOL). METHODS: This was a retrospective single-centre study involving comprehensive clinical data. The Oswestry Disability Index (ODI), visual analog scale (VAS) outcomes, and Scoliosis Research Society (SRS-22) questionnaire were recorded to assess HRQOL. A correlation analysis was performed to determine the association between HRQOL and radiographic parameters. RESULTS: A total of 41 consecutive patients (15 males and 26 females) met the inclusion criteria with a follow-up of 8.62 ± 1.20 years. Factors associated with HRQOL were significantly improved post-operation. Global sagittal parameters, including the sagittal vertebral axis (SVA) and T1 pelvic angle (TPA), and local parameters, including apical vertebral translation (AVT) and apical vertebral rotation (AVR), were significantly improved at the last follow-up. Significantly strong correlations between each clinical and radiographic parameter were demonstrated. Moreover, a multiple linear regression analysis demonstrated that the differences in AVT and AVR were significantly correlated with the difference in lumbar lordosis (LL), which was significantly correlated with the differences in SVA and TPA. CONCLUSION: The surgical treatment of DLS with multisegment TLIF accompanied by Ponte osteotomy and long-level fixations improved the quality of life of patients with a long-term effect. AVR correction is an important factor for LL restoration that significantly correlates with improvements in the sagittal balance parameters SVA and TPA, which are key factors for guaranteeing good HRQOL.

Up-regulation of TßRIII facilitates the osteogenesis of supraspinous ligament-derived fibroblasts from patients with ankylosing spondylitis.

Spinal supraspinous ligament (SL) osteogenesis is the key risk of ankylosing spondylitis (AS), with an unclear pathogenesis. We previously found that transforming growth factor ß1 (TGF-ß1), bone morphogenetic proteins (eg BMP2) and type III TGF-ß1 receptor (TßRIII) expression were markedly up-regulated in AS-SLs. However, the roles of these closely related molecules in AS are unknown. Here, we showed that BMP2, TGF-ß1, TßRIII and S100A4 (a fibroblast marker) were abundant in active osteogenic AS-SL tissues. In vitro, AS-SL fibroblasts (AS-SLFs) showed high BMP2, TGF-ß1 and TßRIII expression and auto-osteogenic capacity. We further evaluated the role of TßRIII in the osteogenesis of normal SLFs. BMP2 combined with TGF-ß1 induced the osteogenesis of TßRIII-overexpressing SLFs, but the activity was lost in SLFs upon TßRIII knockdown. Moreover, our data suggested that BMP2 combined with TGF-ß1 significantly activated both TGF-ß1/Smad signalling and BMP2/Smad/RUNX2 signalling to induce osteogenesis of SLFs with TßRIII up-regulation. Furthermore, our multi-strategy molecular interaction analysis approach indicated that TGF-ß1 presented BMP2 to TßRIII, sequentially facilitating BMP2 recognition by BMPR1A and promoting the osteogenesis of TßRIII-overexpressing SLFs. Collectively, our results indicate that TGF-ß1 combined with BMP2 may participate in the osteogenic differentiation of AS-SLF by acting on up-regulated TßRIII, resulting in excessive activation of both TGF-ß1/Smad and BMP2/BMPR1A/Smad/RUNX2 signalling.

Bacillus alkalicellulosilyticus sp. nov., isolated from extremely alkaline bauxite residue (red mud) site.

A Gram-stain-negative, rod-shaped, facultatively anaerobic, motile and spore-forming strain designated FJAT-44921T was isolated from red mud collected from Chiping County, Shandong Province, China. The 16S rRNA gene sequence result showed that strain FJAT-44921T shared a low sequence identity (96.6%) with the members of the genus Bacillus. Growth was observed at pH 8.0-10.0 (optimum pH 9.0), 10-40 °C (optimum 20-25 °C) with 0-8% (v/w %) NaCl (optimum 4-6 v/w %). FJAT-44921T consists of MK-7 as the isoprenoid quinone and meso-2,6-diaminopimelic acid as the cell-wall diamino acid. The predominant fatty acids were anteiso-C15:0, iso-C15:0, C16:0, and anteiso-C17:0. The polar lipids were diphosphatidylglycerol, phosphatidyl glycerol, phosphatidylmethylethanolamine, unidentified phospholipid, and unidentified aminophospholipid. The genomic DNA G + C content was 37.3 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between FJAT-44921T and other closely related Bacillus members were lower than the recognized threshold values of ANI (95-96%) and dDDH (70%) recommended as the criterion for interspecies identity. The type strain is FJAT-44921T (=CCTCC AB 2016196T =DSM 104630T).

Absorption path extension tunable diode laser absorption spectroscopy system with a dual fiber loop configuration.

Increasing absorbance by lengthening the absorption path is a direct and effective approach to improve the signal-to-noise ratio of infrared gas absorption spectroscopy. However, once the absorption path is extended by designing and optimizing the gas cell structure to a certain extent, a bottleneck will appear due to the difficulties in the optical alignment and the interference effect. A modified tunable diode laser absorption spectroscopy system with a dual fiber loop configuration is proposed that can extend the effective absorption path length of the original multipass cell several times. The relevant theoretical model has been established and its effectiveness has been verified through experiments.

CXCR4 Accelerates Osteoclastogenesis Induced by Non-Small Cell Lung Carcinoma Cells Through Self-Potentiation and VCAM1 Secretion.

BACKGROUND/AIMS: Non-small cell lung carcinoma (NSCLC) metastasis to bone leads to skeletal-related events and a poor quality of life. Unravelling the mechanism of metastasis is crucial for improving survival. Previous work has implicated the role of CXCR4 in bone metastasis; however, the underlying mechanisms are unknown. METHODS: The human bone metastasis tissue samples were obtained from lung cancer patients during surgery with consents. The patients were followed up and the overall survival curve was analysed. The expression of CXCR4, VCAM1, and ADAM17 was measured with real-time PCR, western blot and immunochemistry staining in human tissue or NSCLC cell lines. The effects of CXCR4, soluble VCAM1 and ADAM17 on NSCLC proliferation, migration and invasion were measured with CCK-8, monolayer scratch assay and transwell chamber, respectively. The amount of soluble VCAM1 in the conditioned medium was detected with ELISA. Tartrate-resistant acid phosphatasethe (TRAP) staining was performed to stain the multinucleated cells regarded as osteoclasts. RESULTS: In this study, CXCR4 was found to be highly expressed in bone destruction area of metastatic NSCLC samples and related to poor survival in NSCLC patients with bone metastasis. CXCR4 potentiated NSCLC with enhanced proliferation and invasion abilities, while CXCR4 knockdown significantly suppressed the growth and invasion. Furthermore, CXCR4 promoted lung cancer-induced osteoclast differentiation with increased osteoclast formation. We also found that soluble VCAM1 (sVCAM1) secreted in NSCLC contributed to the osteoclastogenesis induced by CXCR4. The overexpression of CXCR4 increased sVCAM1, and the sVCAM1 secreted from CXCR4-overexpressing NSCLC cells recruited and arrested additional osteoclast progenitors to promote osteoclastogenesis. ADAM17 was confirmed to act as a downstream mediator of CXCR4. The chemical inhibition of ADAM17 with TAPI-2 decreased sVCAM1 secretion and the number of TRAP+ osteoclasts. CONCLUSION: Taken together, these results indicated that CXCR4 potentiated NSCLC and promoted osteoclastogenesis through sVCAM1, which was cleaved by ADAM17. These data support the pivotal role of the cross talk between CXCR4 and ADAM17-VCAM1 in NSCLC-induced bone metastasis.

Anterior reduction and fusion for treatment of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion: A retrospective study.

BACKGROUND: Tear drop fracture of axis represents a very small percentage of injuries of the cervical spine, but there is controversy about the treatment method for tear drop fracture of axis, especially when a large avulsed fragment is significant displacement, which combined with the inferior endplate serious traversed lesion of axis. OBJECTIVE: To evaluate the clinical outcome of anterior reduction, graft fusion of C2-3 and plate fixation in the management of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion of axis. METHODS: There were 7 patients with a massive tear drop fracture of axis combining with inferior endplate serious traversed lesion. The avulsed ratio of inferior endplate of axis was 46.8 ± 13.4%, the average angle of rotation of the avulsed fragment was 30.4 ± 11.7, and the average displacement was 7.7 ± 2.8 mm. The posterior displacement of axis body was observed with three patients. All patients underwent anterior reduction, graft fusion of C2-3 and plate fixation with high anterior cervical retropharyngeal approach. The follow-up ranges from 2 years to 5 years. RESULTS: In all cases, tear drop fracture was reduced completely, avulsed fragment got bony healing, and bone graft achieved bony fusion at C2-3. There were no local angle deformity and rotated deformity in all patients, and there were normal physiological lordosis and good stabilization of upper cervical spine. The neurological function of one patient with American Spine Injury Association (ASIA) impairment scale type D was improved to type E postoperatively. Six patients without neurological lesion had no neurological syndrome after operation. CONCLUSIONS: Anterior surgical procedures would be an effective treatment of massive tear drop fracture of axis combining with inferior endplate serious traversed lesion. Complete reduction, sufficient stabilization and normal physiological lordosis of upper cervical spine could be achieved postoperatively.

Distinguishing characteristics of stem cells derived from different anatomical regions of human degenerated intervertebral discs.

INTRODUCTION: Several types of stem cells have been successfully demonstrated to exist in the human degenerated intervertebral disc (IVD), which is composed of annulus fibrosus (AF), nucleus pulposus (NP) and cartilage endplate (CEP). However, the differences in the biological characteristics among these and bone marrow derived mesenchymal stem cells (BM-MSCs) remain unclear. MATERIALS AND METHODS: To investigate this issue, cells were harvested from human AF, NP, CEP, and bone marrow, respectively; passage 2 cells were selected using the agarose suspension culture system to obtain stem cell clones. Following expansion in vitro, stem cells from different anatomical regions were compared regarding the morphology, proliferation ability, immunophenotypic expression, and multi-lineage differentiation capacity. In addition, stem cell-alginate bead compositions were constructed for the comparison of DNA and sGAG content. RESULTS: There were subtle differences regarding cell morphology, but no significant differences in proliferation ability among the four types of stem cells. For the immunophenotypic analysis, all stem cells basically fulfilled the criteria for mesenchymal stem cells (MSCs), which have been published by the International Society for Cellular Therapy (ISCT), with a significant difference in CD105 expression. A comparison of the osteogenic capacities indicated: cartilage endplate-derived stem cells (CESCs) > annulus fibrosus-derived stem cells (AFSCs) > BM-MSCs > nucleus pulposus-derived stem cells (NPSCs). The chondrogenesis difference was similar to osteogenesis. For adipogenesis: BM-MSCs >NPSCs >CESCs >AFSCs. In the stem cell/alginate composition, the CESCs consistently showed the superior chondrogenic potential among all those cell types. CONCLUSIONS: Our data indicated that all the four types of stem cells shared some similar biological properties (regarding shape, proliferation ability and immunophenotypic expression). CESCs, which had the strongest osteogenic and chondrogenic potentials, may serve as excellent seed cells for NP/cartilage or bone tissue engineering.

Prostate cancer cells induce osteoblastic differentiation via semaphorin 3A.

BACKGROUND: Prostate cancer metastasis to bone is the second most commonly diagnosed malignant disease among men worldwide. Such metastatic disease is characterized by the presence of osteoblastic bone lesions, and is associated with high rates of mortality. However, the various mechanisms involved in prostate cancer-induced osteoblastic differentiation have not been fully explored. Semaphorin 3A (Sema 3A) is a newly identified regulator of bone metabolism which stimulates differentiation of pre-osteoblastic cells under physiological conditions. We investigated in this study whether prostate cancer cells can mediate osteoblastic activity through Sema 3A. METHODS: We cultured osteoprogenitor MC3T3-E1 cells in prostate cancer-conditioned medium, and analyzed levels of Sema 3A protein in diverse prostate cancer cell lines to identify cell lines in which Sema 3A production showed a positive correlation with osteo-stimulation. C4-2 cells were stably transfected with Sema 3A short hairpin RNA to further determine whether Sema 3A contributes to the ability of C4-2 cells to induce osteoblastic differentiation. RESULTS: Down-regulation of Sema 3A expression decreased indicators of C4-2 CM-induced osteoblastic differentiation, including alkaline phosphatase production and mineralization. Additionally, silencing or neutralizing Sema 3A in C4-2 cells resulted in diminished ß-catenin expression in osteogenitor MC3T3-E1 cells. CONCLUSIONS: Our results suggest that prostate cancer-induced osteoblastic differentiation is at least partially mediated by Sema 3A, and may be regulated by the ß-catenin signalling pathway. Sema 3A may represent a novel target for treatment of prostate cancer-induced osteoblastic lesions.

CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis.

Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients.

Quetiapine inhibits osteoclastogenesis and prevents human breast cancer-induced bone loss through suppression of the RANKL-mediated MAPK and NF-κB signaling pathways.

Bone loss is one of the major complications of advanced cancers such as breast cancer, prostate cancer, and lung cancer. Extensive research has revealed that the receptor activator of NF-κB ligand (RANKL), which is considered to be a key factor in osteoclast differentiation, plays an important role in cancer-associated bone resorption. Therefore, agents that can suppress this bone loss have therapeutic potential. In this study, we detected whether quetiapine (QUE), a commonly used atypical antipsychotic drug, can inhibit RANKL-induced osteoclast differentiation in vitro and prevent human breast cancer-induced bone loss in vivo. RAW 264.7 cells and bone marrow-derived macrophages (BMMs) were used to detect inhibitory effect of QUE on osteoclastogenesis in vitro. Mouse model of breast cancer metastasis to bone was used to test suppressive effect of QUE on breast cancer-induced bone loss in vivo. Our results show that QUE can inhibit RANKL-induced osteoclast differentiation from RAW 264.7 cells and BMMs without signs of cytotoxicity. Moreover, QUE reduced the occurrence of MDA-MB-231 cell-induced osteolytic bone loss by suppressing the differentiation of osteoclasts. Finally, molecular analysis revealed that it is by inhibiting RANKL-mediated MAPK and NF-κB signaling pathways that QUE suppressed the osteoclast differentiation. We demonstrate, for the first time, the novel suppressive effects of QUE on RANKL-induced osteoclast differentiation in vitro and human breast cancer-induced bone loss in vivo, suggesting that QUE may be a potential therapeutic drug for osteolysis treatment.

Comparison of Hybrid Surgery Incorporating Anterior Cervical Discectomy and Fusion and Artificial Arthroplasty versus Multilevel Fusion for Multilevel Cervical Spondylosis: A Meta-Analysis.

BACKGROUND Few studies have reported the safety and efficacy of hybrid surgery (HS), and some of the studies comparing HS with ACDF have reported conflicting results. We conducted this meta-analysis to clarify the advantages of HS in the treatment of multilevel cervical spondylosis. MATERIAL AND METHODS We performed a systematic literature search in PubMed, Medline, and CNKI to identify relevant controlled trials published up to October 2015. The standardized mean difference (SMD) and 95% confidence interval (95% CI) of the perioperative parameters, visual analogue scale pain score (VAS), neck disability index (NDI), and range of motion (ROM) of C2-C7 and adjacent segments were calculated. We also analyzed complications and Odom scale scores using risk difference (RD) and 95% CI. RESULTS In total, 7 studies were included. The pooled data exhibited significant differences in blood loss between the 2 groups. However, there was no evidence indicating significant differences in operation time, complications, VAS, NDI, or Odom scale scores. Compared with the ACDF group, the HS group exhibited significantly protected C2-C7 ROM and reduced adjacent-segment ROM. CONCLUSIONS The safety of HS may be as good as that of ACDF. Furthermore, HS is superior to ACDF in conserving cervical spine ROM and decreasing adjacent-segment ROM. However, the results should be accepted cautiously due to the limitations of the study. Studies with larger sample sizes and longer follow-up periods are required to confirm and update the results of the present study.

Single-nucleotide polymorphisms of the PRKCG gene and osteosarcoma susceptibility.

The objective of this study was to explore the relationship between single-nucleotide polymorphisms (SNPs) of the protein kinase C gamma (PRKCG) gene and osteosarcoma susceptibility in Chinese Han population. A total of 610 cases of osteosarcoma patients and 610 healthy individuals were enrolled in this study. TaqMan method was used to compare genotypes and the allelic distribution frequency of three SNPs (rs454006, rs2242245, and rs8103851) in the PRKGG gene between osteosarcoma patients and healthy individuals. Osteosarcoma patients were grouped according to different clinical parameters (age, gender, pathological types, tumor location, Enneking staging, tumor metastasis and treatment) to compare genotype and allele frequency among different groups as well as to explore the relationship between gene polymorphisms and different clinical parameters. The rs454006 polymorphisms of the PRKCG gene include the CC, CT, and TT genotypes. The differences in genotype frequency and allele frequency between osteosarcoma patients and healthy individuals were significant (both P < 0.001). There was no significant different between osteosarcoma patients and healthy individuals in rs8103851 and rs2242245 polymorphisms of the PRKCG gene (both P > 0.05). The differences of the rs8103851 genotype frequency and allele frequency in patients with metastatic osteosarcoma and patients without metastasis were significant (both P < 0.001). The distribution frequencies of the CG and GG genotypes as well as the G allele in patients with metastatic osteosarcoma were higher than in patients without metastasis. The genotype frequency and allele frequency of rs454006 and rs2242245 did not correlate with clinical parameters. The rs454006 polymorphism of the PRKCG gene correlated to osteosarcoma susceptibility and might increase the risk of osteosarcoma. The rs8103851 correlated to metastatic osteosarcoma and could be risk factors for metastatic osteosarcoma.

Prevalence and Risk Factors for Cervical Adjacent Segment Disease and Analysis of the Clinical Effect of Revision Surgery: A Minimum of 5 Years' Follow-Up.

STUDY DESIGN: A retrospective study was performed. OBJECTIVE: To investigate the prevalence and risk factors for adjacent segment disease (ASD) after anterior cervical discectomy and fusion (ACDF) and the clinical efficacy of revision surgery. METHOD: A total of 219 patients treated with ACDF were analyzed retrospectively. Demographic characteristics, including age, sex, body mass index (BMI) and bone mineral density (BMD), and radiographic measurements, including C2-C7 cervical sagittal vertical axis (cSVA), T1 slope (T1S), thoracic inlet angle (TIA) and C2-C7 Cobb angle, were analyzed. Modified Japanese Orthopaedic Association (mJOA) score and visual analog scale (VAS) score were used to evaluate patient function. Parameters were analyzed with Student's t test, and potential risk factors for ASD were further analyzed with multivariate logistic regression analysis. RESULTS: The incidence of ASD after ACDF surgeries was 21%. The severity of osteoporosis, BMI and C2-C7 cSVA were significantly higher in the ASD group than in the NASD group (P < .05). The preoperative and postoperative TIAs were lower in the ASD group (P < .05). Multivariate logistic regression analysis showed that a high BMI, severe osteoporosis and a high C2-C7 cSVA were risk factors for ASD after ACDF (P < .05). The postoperative TIA and postoperative T1S were also correlated with ASD (P < .05). CONCLUSION: Patients with a high BMI, severe osteoporosis, and a large C2-C7 cSVA after ACDF have a higher risk of ASD, while a large T1S and TIA may be protective factors. In addition, revision surgery can restore cervical spine balance in patients with ASD and promote better clinical outcomes.

Cells scaffold complex for Intervertebral disc Anulus Fibrosus tissue engineering: in vitro culture and product analysis.

The study was designed to investigate feasibility of tissue culture in vitro utilizing static culture method. Annulus fibrosus cells obtained from spine of rabbits were cultured. Results showed that fibrous tissue infiltration could be detected in shallow layer. With extended time, tissue infiltration depth increased, but there were still a large amount of holes in central part. Fibrous tissue infiltration was detected in the control side products and inner infiltration wasn't obvious. Hydroxyproline content of the control side products gradually increased with extended culture time. Hydroxyproline content of the control side products in the third and fourth month was significantly higher than that in the first month, but lower than those of the experimental side products and normal annulus fibrosus cells. DNA content of the control side products in the third and fourth month was significantly increased compared to the first month. DNA content of the control side products at each phase point was significantly lower than that of the experimental side and normal annulus fibrosus cells. Furthermore, there was lower expression levels of the type I, II collagen mRNA and protein in the experimental side scaffolds compared to the control side product. This study demonstrates the successful formation of Intervertebral disc Anulus Fibrosus in vitro by static culture method.

Risk Factors of Bone Nonfusion After Spinal Tuberculosis Debridement Bone Graft Fusion and Internal Fixation.

Objective: To retrospectively analyze bone graft nonfusion risk factors in spinal tuberculosis patients after lesion debridement, bone graft fusion and internal fixation. Methods: The clinical data of 131 patients who underwent spinal tuberculosis debridement, bone graft fusion and internal fixation in our hospital from March 2015 to March 2018 were retrospectively analyzed. The patients were divided into two groups according to bone fusion after the operation; there were 37 patients in the nonfusion group and 94 in the fusion group. The basic information and follow-up data of the patients were collected to evaluate the risk factors for bone graft nonfusion 1 year after surgery. Results: The severity of osteoporosis in the nonfusion group was significantly greater than that in the fusion group (p < 0.05). There were statistically significant differences between the two groups in terms of continuous multisegment status, disease duration, intraoperative surgical methods and whether patients received standardized drug treatment for 12 months after surgery (p < 0.05). Multivariate logistic regression analysis showed that long disease duration, posterior approach, and degree of osteoporosis were risk factors for postoperative bone graft nonfusion (OR > 1, p < 0.05), while standard drug treatment for 1 year after surgery was a protective factor (OR < 1, p < 0.05). Conclusion: Spinal tuberculosis patients who had a long disease course, who underwent simple posterior debridement, or who had severe osteoporosis had a higher risk of bone graft nonfusion after surgery. Tuberculosis treatment is beneficial for the osseous fusion of the postoperative bone graft area.

Spindle and Kinetochore-associated Family Genes are Prognostic and Predictive Biomarkers in Hepatocellular Carcinoma.

Background and Aims: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors. Spindle and kinetochore-associated (SKA) family genes are essential for the maintenance of the metaphase plate and spindle checkpoint silencing during mitosis. Recent studies have indicated that dysregulation of SKA family genes induces tumorigenesis, tumor progression, and chemoresistance via modulation of cell cycle and DNA replication. However, the differential transcription of SKAs in the context of HCC and its prognostic significance has not been demonstrated. Methods: Bioinformatics analyses were performed using TCGA, ONCOMINE, HCCDB, Kaplan-Meier plotter, STRING, GEPIA databases. qRT-PCR, western blot, and functional assays were utilized for in vitro experiments. Results: We found remarkable upregulation of transcripts of SKA family genes in HCC samples compared with normal liver samples on bioinformatics analyses and in vitro validation. Interaction analysis and enrichment analysis showed that SKA family members were mainly related to microtubule motor activity, mitosis, and cell cycle. Immuno-infiltration analysis showed a correlation of all SKA family genes with various immune cell subsets, especially T helper 2 (Th2) cells. Transcriptional levels of SKA family members were positively associated with histologic grade, T stage, and α-fetoprotein in HCC patients. Receiver operating characteristic curve analysis demonstrated a strong predictive ability of SKA1/2/3 for HCC. Increased expression of these SKAs was associated with unfavorable overall survival, progression-free survival, and disease-specific survival. On Cox proportional hazards regression analyses, SKA1 upregulation and pathological staging were independent predictors of overall survival and disease-specific survival of HCC patients. Finally, clinical tissue microarray validation and in vitro functional assays revealed SKA1 acts an important regulatory role in tumor malignant behavior. Conclusions: SKA family members may potentially serve as diagnostic and prognostic markers in the context of HCC. The correlation between SKAs and immune cell infiltration provides a promising research direction for SKA-targeted immunotherapeutics for HCC.

Retrospective Analysis of Sagittal Balance Parameters and Clinical Efficacy After Short-Segment Anterior Cervical Spine Surgery with Different Fusion Devices.

Objective: To compare the cervical sagittal balance parameters and clinical efficacy of three fusion devices after short-segment anterior cervical discectomy and fusion. Patients and Methods: Retrospectively analyzed 516 patients with cervical spondylosis who underwent surgery at our hospital from May 2013 to May 2019. All patients had complete data and were divided into three groups according to the selected fusion cage. Neck and upper limb pain were assessed by the visual analog scale (VAS) score. Neurological function was evaluated by the modified Japanese Orthopedics Society (mJOA) score. Also, the curvature of the cervical spine and the occurrence of dysphagia were observed. Results: There were no significant differences in the general information, thoracic inlet angle, T1 slope, or surgical data among the groups (p>0.05). There were significant differences in the scores between pre- and postoperatively in the different groups (p<0.05). There were no significant differences in the C2-C7 Cobb angle or C2-C7 sagittal vertebral axis before the operation among the groups (p>0.05). There was a significant difference in the correction and loss of correction among the groups postoperatively and on follow-up (p>0.05). Dysphagia was less likely in the Zero-P VA fusion group than in the other two groups. Conclusion: Different fusion instruments can relieve the symptoms. In the Prodisc-C Vivo group, no significant improvement in cervical sagittal balance was achieved. A good effect on improving sagittal balance was observed in both the Zero-P VA fusion and Skyline anterior cervical titanium plate groups, but a better effect on preventing dysphagia was observed in the Zero-PVA fusion group.

Effect of vascular endothelial growth factor 121 adenovirus transduction in rabbit model of femur head necrosis.

BACKGROUND: Our objective was to observe the role of vascular endothelial growth factor (VEGF) 121 gene transfer in promoting vascular reconstruction and bone repair in femur head necrosis of rabbits. METHODS: The femoral head necrosis model was induced by injection with ethanol. The necrotic femoral head was transfected with a human adenoviral vector expressing VEGF (Ad-hVEGF121). Bone formation in the subchondral necrotic region was analyzed using histology, by measuring the bone mineral density value, and by observing bone trabecular morphology using image analysis. RESULTS: Revascularization level, bone formation rate, bone quality and quantity, and mineralization level in the subchondral necrotic region of the gene transfection group were significantly higher than the control groups. The control groups had more subchondral bone resorption compared with the gene transfection group. CONCLUSION: VEGF might promote bone formation and revascularization in the subchondral necrotic region of the femoral head, indirectly protecting the necrotic bone trabecula from absorption and avoiding a reduction in the mechanical function of the subchondral region.

The intermediate clinical outcome and its limitations of Bryan cervical arthroplasty for treatment of cervical disc herniation.

STUDY DESIGN: This is a prospective, consecutive series study to determine the role of the Bryan artificial cervical disc replacement to treat the isolated cervical disc herniation for Chinese patients. OBJECTIVE: To evaluate the intermediate clinical outcome and its limitations of Bryan cervical disc replacement in the management of isolated cervical disc herniation in Chinese patients. Observing neurological improvement and the radiographic finding. SUMMARY OF BACKGROUND DATA: Most people believe that anterior cervical fusion is a factor that shall not be ignored in adjacent segment degeneration. Artificial cervical disc replacement, as a nonfusion technique, may offer a solution to this problem. The clinical outcome of cervical arthroplasty in oriental patients is not often seen in English literature. The variation of anatomic index in Asian patients was also not considered enough. METHODS: There were consecutive series of 45 patients with cervical disc herniation. The herniated disc was located at C3-4 in 2 cases, at C4-5 in 8 cases, at C5-6 in 24 cases, at C6-7 in 5 cases, at C4-5, 5-6 in 2 cases, at C3,4, 5-6 in 1 cases, and at C 5-6, 6.7 in 3 cases. There were 19 patients with myelopathy and 26 patients with radiculopathy. A total of 51 sets of Bryan cervical disc prosthesis were implanted. The follow-up ranges from 24 to 70 months. The clinical symptom and the neurological function were evaluated. The level of stableness and mobility at the implanting location were observed on dynamic radiograph postoperatively. RESULTS: A total of 51 Bryan cervical disc prosthesis were implanted. Single-level disc was replaced in 39 cases whereas bilevel in 6 cases. The follow-up ranges from 24 to 70 months, with an average of 35 months. Patients showed significant improvement in neurological symptoms. The JOA score (17 points) was from 10.2 increased to 15.4 at final follow-up. The neck disability index was from 43.5 reduced to 28.4 at final follow-up. The clinical success (excellent/good/fair) according to Odom' Criteria were 89.8%. The average range of motion at implant level was 9.3 degrees, postoperatively. Migration of artificial disc greater than 2 mm was not observed. Resorption at the inferior edge of anterior surface of upper vertebral body were seen in 3 patients, Two patients had II grade heterotopic ossification. One patient had a definite spontaneous fusion of treated segment after 4 years of follow-up. There was some difficulty for exact matched implant in small group patients owing to the variation of anatomic index in oriental patients. CONCLUSIONS: Cervical arthroplasty had a good intermediate clinical outcome for oriental patients. Definite stabilization and satisfactory mobility were achieved after surgery, with significant neurological symptom improvement observed. For better matched implant, more shapes/sizes of artificial cervical disc need to be made available for the oriental patients.