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.

CaCP15 Gene Negatively Regulates Salt and Osmotic Stress Responses in Capsicum annuum L.

Salt and osmotic stress seriously restrict the growth, development, and productivity of horticultural crops in the greenhouse. The papain-like cysteine proteases (PLCPs) participate in multi-stress responses in plants. We previously demonstrated that salt and osmotic stress affect cysteine protease 15 of pepper (Capsicum annuum L.) (CaCP15); however, the role of CaCP15 in salt and osmotic stress responses is unknown. Here, the function of CaCP15 in regulating pepper salt and osmotic stress resistance was explored. Pepper plants were subjected to abiotic (sodium chloride, mannitol, salicylic acid, ethrel, methyl jasmonate, etc.) and biotic stress (Phytophthora capsici inoculation). The CaCP15 was silenced through the virus-induced gene silencing (VIGS) and transiently overexpressed in pepper plants. The full-length CaCP15 fragment is 1568 bp, with an open reading frame of 1032 bp, encoding a 343 amino acid protein. CaCP15 is a senescence-associated gene 12 (SAG12) subfamily member containing two highly conserved domains, Inhibitor 129 and Peptidase_C1. CaCP15 expression was the highest in the stems of pepper plants. The expression was induced by salicylic acid, ethrel, methyl jasmonate, and was infected by Phytophthora capsici inoculation. Furthermore, CaCP15 was upregulated under salt and osmotic stress, and CaCP15 silencing in pepper enhanced salt and mannitol stress resistance. Conversely, transient overexpression of CaCP15 increased the sensitivity to salt and osmotic stress by reducing the antioxidant enzyme activities and negatively regulating the stress-related genes. This study indicates that CaCP15 negatively regulates salt and osmotic stress resistance in pepper via the ROS-scavenging.

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.

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.

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.

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.

Corrigendum: CDT1 is a Novel Prognostic and Predictive Biomarkers for Hepatocellular Carcinoma.

[This corrects the article DOI: 10.3389/fonc.2021.721644.].

BCI Suppresses RANKL-Mediated Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss.

Osteoporosis is a common aging-related metabolic disease that mainly occurs in older adults and postmenopausal women. Despite advances in anti-osteoporosis treatment, outcomes remain unsatisfactory due to detrimental side effects. BCI hydrochloride (BCI), a selective dual-specificity phosphatase 6 (DUSP6) inhibitor, is associated with multiple cellular functions, including inhibiting tumor growth and macrophage inflammation; however, its role in regulating osteoclast differentiation remains unknown. Here, we revealed that treatment with BCI attenuated RANKL-mediated osteoclast differentiation in vitro and alleviated ovariectomy-induced osteoporosis without obvious toxicity. Specifically, BCI disrupted F-actin ring formation and bone-resorption activity and decreased osteoclast-specific gene and protein levels in a dose-dependent manner. KEGG pathway analysis, GSEA based on transcriptome sequencing, and western blot results suggested that BCI inhibited RANKL-induced osteoclastogenesis by restraining STAT3 and NF-κB signaling and attenuating NF-κB/p65 interaction with NFATc1. These results revealed that BCI treatment prevented postmenopausal osteoporosis and might represent an effective approach for treating osteoporosis.

Incidence and Risk Factors for Adjacent Segment Disease After Transforaminal Lumbar Interbody Fusion in Patients with Lumbar Degenerative Diseases.

PURPOSE: To explore the incidence and risk factors for adjacent segment disease (ASD) in patients with lumbar degenerative diseases after transforaminal lumbar interbody fusion (TLIF). PATIENTS AND METHODS: The clinical data of 1258 patients who underwent transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative diseases in our hospital from January 2011 to December 2017 were retrospectively analyzed. Patients were divided into the ASD group and non-ASD (N-ASD) group, and the incidence of ASD was calculated. We compared age, BMI, comorbidities, surgery-related parameters, and imaging parameters before surgery between the two groups and used univariate analysis and logistic regression analysis to explore the risk factors for ASD. RESULTS: Among the 1258 patients who underwent TLIF due to lumbar degenerative diseases, 65 patients developed ASD and received surgical treatment for it, for an incidence of 5.2%. The average onset time of ASD was 68.3±25.1 (20-123) months. Univariate analysis showed that BMI, hypertension, preoperative adjacent segment disc degeneration and preoperative adjacent intervertebral disc height were significantly different between the ASD and N-ASD groups (P< 0.05). Incorporating the above indicators into the logistic regression model, the results showed that BMI and preoperative adjacent intervertebral disc degeneration were risk factors for ASD after TLIF. CONCLUSION: The incidence of ASD after TLIF in patients with lumbar degenerative disease is approximately 5.2%. High BMI and preoperative adjacent segment disc degeneration are risk factors for ASD after TLIF.

CDT1 Is a Novel Prognostic and Predictive Biomarkers for Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors endangering human health and life in the 21st century. Chromatin licensing and DNA replication factor 1 (CDT1) is an important regulator of DNA replication licensing, which is essential for initiation of DNA replication. CDT1 overexpression in several human cancers reportedly leads to abnormal cell replication, activates DNA damage checkpoints, and predisposes malignant transformation. However, the abnormal expression of CDT1 in HCC and its diagnostic and prognostic value remains to be elucidated. METHODS: TCGA, ONCOMINE, UALCAN, HCCDB, HPA, Kaplan-Meier plotter, STRING, GEPIA, GeneMANIA, and TIMER were conducted for bioinformatics analysis. CDT1 protein expression was evaluated by immunohistochemistry in HCC tissues through a tissue microarray. qRT-PCR, western blot and a cohort of functional experiments were performed for in vitro validation. RESULTS: In this study, we discovered remarkably upregulated transcription of CDT1 in HCC samples relative to normal liver samples through bioinformatic analysis, which was further verified in clinical tissue microarray samples and in vitro experiments. Moreover, the transcriptional level of CDT1 in HCC samples was positively associated with clinical parameters such as clinical tumor stage. Survival, logistic regression, and Cox regression analyses revealed the significant clinical prognostic value of CDT1 expression in HCC. The receiver operating characteristic curve and nomogram analysis results demonstrated the strong predictive ability of CDT1 in HCC. Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analyses indicated that CDT1 was mainly associated with the cell cycle, DNA repair, and DNA replication. We further demonstrated the significant correlation between CDT1 and minichromosome maintenance (MCM) family genes, revealing abnormal expression and prognostic significance of MCMs in HCC. Immune infiltration analysis indicated that CDT1 was significantly associated with immune cell subsets and affected the survival of HCC patients. Finally, knockdown of CDT1 decreased, whereas overexpression of CDT1 promoted the proliferation, migration, invasion of HCC cells in vitro. CONCLUSIONS: Our study findings demonstrate the potential diagnostic and prognostic significance of CDT1 expression in HCC, and elucidate the potential molecular mechanism underlying its role in promoting the occurrence and development of liver cancer. These results may provide new opportunities and research paths for targeted therapies in HCC.

Nox4 Promotes RANKL-Induced Autophagy and Osteoclastogenesis via Activating ROS/PERK/eIF-2α/ATF4 Pathway.

Receptor activator of nuclear factor-κB ligand (RANKL) has been found to induce osteoclastogenesis and bone resorption. However, the underlying molecular mechanisms remain unclear. Via conducting a series of biochemical experiments with in vitro cell lines, this study investigated the role and mechanism of NADPH oxidase 4 (Nox4) in RANKL-induced autophagy and osteoclastogenesis. In the current study, we found that RANKL dramatically induced autophagy and osteoclastogenesis, inhibition of autophagy with chloroquine (CQ) markedly attenuates RANKL-induced osteoclastogenesis. Interestingly, we found that the protein level of Nox4 was remarkably upregulated by RANKL treatment. Inhibition of Nox4 by 5-O-methyl quercetin or knockdown of Nox4 with specific shRNA markedly attenuated RANKL-induced autophagy and osteoclastogenesis. Furthermore, we found that Nox4 stimulated the production of nonmitochondrial reactive oxygen species (ROS), activating the critical unfolded protein response (UPR)-related signaling pathway PERK/eIF-2α/ATF4, leading to RANKL-induced autophagy and osteoclastogenesis. Blocking the activation of PERK/eIF-2α/ATF4 signaling pathway either by Nox4 shRNA, ROS scavenger (NAC) or PERK inhibitor (GSK2606414) significantly inhibited autophagy during RANKL-induced osteoclastogenesis. Collectively, this study reveals that Nox4 promotes RANKL-induced autophagy and osteoclastogenesis via activating ROS/PERK/eIF-2α/ATF4 pathway, suggesting that the pathway may be a novel potential therapeutic target for osteoclastogenesis-related disease.

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.

NeuroRegen Scaffolds Combined with Autologous Bone Marrow Mononuclear Cells for the Repair of Acute Complete Spinal Cord Injury: A 3-Year Clinical Study.

Spinal cord injury (SCI) remains among the most challenging pathologies worldwide and has limited therapeutic possibilities and a very bleak prognosis. Biomaterials and stem cell transplantation are promising treatments for functional recovery in SCI. Seven patients with acute complete SCI diagnosed by a combination of methods were included in the study, and different lengths (2.0-6.0 cm) of necrotic spinal cord tissue were surgically cleaned under intraoperative neurophysiological monitoring. Subsequently, NeuroRegen scaffolds loaded with autologous bone marrow mononuclear cells (BMMCs) were implanted into the cleaned site. All patients participated in 6 months of rehabilitation and at least 3 years of clinical follow-up. No adverse symptoms associated with stem cell or functional scaffold implantation were observed during the 3-year follow-up period. Additionally, partial shallow sensory and autonomic nervous functional improvements were observed in some patients, but no motor function recovery was observed. Magnetic resonance imaging suggested that NeuroRegen scaffold implantation supported injured spinal cord continuity after treatment. These findings indicate that implantation of NeuroRegen scaffolds combined with stem cells may serve as a safe and promising clinical treatment for patients with acute complete SCI. However, determining the therapeutic effects and exact application methods still requires further study.

Preliminary investigation of bilateral internal iliac artery ligation and anterior tumor separation through laparoscopy before posterior resection of a giant sacral tumor.

BACKGROUND: Surgical is the optimal therapeutic strategy for sacral tumors, and complete resection can effectively improve the recurrence and survival rates. However, the specialized anatomy, massive bleeding and adhesion to the anterior tissue, especially that caused by giant sacral tumors, makes complete resection difficult. The laparoscopic technique provides a new method to resect sacral tumors. METHODS: 34 patients with primary giant sacral tumors who underwent surgical resection were enrolled. After bilateral internal iliac artery ligation and anterior laparoscopic tumor separation, the sacral tumors were successfully resected posteriorly. The clinical, radiological and follow-up data were collected and analyzed. RESULTS: The average operative time was 276.47 min and that for laparoscopy was 76.24 min. The average intraoperative blood loss was 1757.64 ml. No complications associated with laparoscopic surgery, such as intestinal, urinary tract, or vascular injuries, occurred. Ten patients (29.41%) had perioperative complications, including infection, unhealed wounds, and cerebrospinal fluid leaks in 10, 5 and 2 patients, respectively. Patients with complications had significantly longer total (55.00 ± 34.53 vs 25.13 ± 14.60, P = 0.001) and postoperative (39.10 ± 30.61 vs 14.83 ± 10.00, P = 0.002) hospitalization stays than patients without complications. Postoperatively, bowel and bladder dysfunction, intestinal obstruction, pain, and perianal numbness occurred in 21, 5, 8, and 2 patients, respectively. The recurrence rate was 11.76%. CONCLUSIONS: Laparoscopically assisted sacral tumor resection is a technically feasible and effective surgical method to resect giant sacral tumors, with the advantages of reduced operative blood loss during internal iliac artery ligation and anterior tumor separation.

Single-stage posterior total en bloc spondylectomy in the treatment of lumbar spinal metastases.

OBJECTIVE: To report the clinical and radiographic outcomes of single-stage posterior total en bloc spondylectomy (TES) of lumbar spinal metastases. PATIENTS AND METHODS: From January 2012 to January 2015, 20 consecutive cases with lumbar spinal metastases who received single-stage posterior TES were retrospectively analyzed. A visual analog scale (VAS) was used to evaluate patients' pain status, American Spinal Injury Association (ASIA) classification was used to evaluate neurological status, and Eastern Cooperative Oncology Group (ECOG) score system was used to evaluate patients' performance status at pre- and post-operation and final follow-up. In addition, Intraoperative blood loss, operative time, postoperative complications, local kyphosis angle, and the postoperative duration of hospital stay were analyzed. RESULTS: The median follow-up time was 16 months (ranging from 3 to 39 months), and 4 patients were still alive at the last follow-up. The mean amount of intraoperative blood loss and operation time was 970 mL and 232.5 min, respectively. The average VAS score improved from 7.5 preoperative to 2.8 postoperative and 3.2 at the last follow-up. Postoperative complications occurred in 3 cases. Sixteen patients died within 2 years after surgery, 10 of which died within 1 year. In the remaining 4 patients, the mean follow-up period was 37.25 months. One case of local recurrence occurred but no implant failure presented during follow-up. CONCLUSIONS: Single-stage posterior TES is a challenging but rewarding procedure in the treatment of lumbar spinal metastases. Due to unique anatomy and biomechanics, surgeons should be aware of important vessels, and nerve root injury should be avoided.

[Risk factors analysis of coronal imbalance after posterior long-level fixation and transforaminal lumbar interbody fusion for degenerative lumbar scoliosis].

OBJECTIVE: To explore the risk factors of coronal imbalance after posterior long-level fixation and fusion for degenerative lumbar scoliosis. METHODS: Retrospectivly analyzed the clinical records of 41 patients with degenerative lumbar scoliosis who had received posterior long-level fixation and fusion with selective transforaminal lumbar interbody fusion (TLIF) accompanied by Ponte osteotomy between August 2011 and July 2016. Patients were divided into imbalance group (group A, 11 cases) and balance group (group B, 30 cases) according to state of coronal imbalance measured at last follow-up. The radiographic parameters at preoperation and last follow-up were measured, and the variance of preoperative and last follow-up parameters were calculated. The radiographic parameters included coronal Cobb angle, coronal balance distance (CBD), apical vertebral translation (AVT), apical vertebral rotation (AVR), Cobb angle of lumbar sacral curve (LSC), and L 5 tilt angle (L 5TA). Univariate analysis was performed for the factors including gender, age, preoperative T value of bone mineral density, number of instrumented vertebra, upper and lower instrumented vertebra, segments of TLIF, decompression, and Ponte osteotomy, as well as the continuous variables of preoperative imaging parameters with significant difference were converted into two-category variables, obtained the influence factors of postoperative coronal imbalance. Multivariate logistic regression analysis was performed to verify the risk factors from the preliminary screened influence factors and the variance of imaging parameters with significant difference between the two groups. RESULTS: The follow-up time of groups A and B was (3.76±1.02) years and (3.56±1.03) years respectively, there was no significant difference between the two groups ( t=0.547, P=0.587). The coronal Cobb angle, AVT, LSC Cobb angle, and L 5TA in group A were significantly higher than those in group B before operation ( P<0.05), and all the imaging parameters in group A were significantly higher than those in group B at last follow-up ( P<0.05). There was no significant difference between the two groups in parameters including the variance of coronal Cobb angle, AVT, and LSC Cobb angle before and after operation ( P>0.05), and there were significant differences between the two groups in parameters including the variance of CBD, L 5TA, and AVR ( P<0.05). Univariate analysis showed that preoperative L 5TA was the influencing factor of postoperative coronal imbalance ( P<0.05). Multivariate logistic regression analysis showed that preoperative L 5TA≥15° was an independent risk factor of postoperative coronal imbalance, and variance of pre- and post-operative AVR was a protective factor. CONCLUSION: Preoperative L 5TA≥15° is an independent risk factor for coronal imbalance in patients with degenerative lumbar scoliosis after posterior long-level fixation and fusion.

Sema4D expression and secretion are increased by HIF-1α and inhibit osteogenesis in bone metastases of lung cancer.

Most lung cancer bone metastasis are characterized by osteolytic destruction and osteoblastic activity is significantly decreased, suggesting that hypoxia may play a critical role in the process, but the underlying mechanisms remain unknown. Semaphorin 4D (Sema4D) is a recently discovered osteogenic inhibitory factor that is expressed at high levels in lung cancers. Here, CoCl2-induced hypoxia significantly enhanced the inhibitory effect of lung cancer cell conditioned media on osteoblast differentiation by inducing the expression and secretion of Sema4D in a HIF-1α- but not HIF-2α-dependent manner. Moreover, HIF-1α directly regulated Sema4D expression by binding to bases 1171 to 798 in the Sema4D promoter. Furthermore, hypoxia increased Sema4D secretion by upregulating a disintegrin and metalloproteinase 17 (ADAM17) expression in lung cancer in a HIF-1α-dependent manner. In bone metastasis samples from 49 patients with lung cancer, Sema4D and ADAM17 expression significantly correlated with HIF-1α expression and strongly correlated with a poor differentiation status and osteolytic bone destruction. These results provide the first evidence that HIF-1α-induced Sema4D expression and secretion play important roles in lung cancer osteolytic bone metastasis by inhibiting osteoblast differentiation, thereby providing potential strategies for the treatment of bone metastasis via targeting osteoblasts.

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.

Prognostic Factors and Comparison of Conservative Treatment, Percutaneous Vertebroplasty, and Open Surgery in the Treatment of Spinal Metastases from Lung Cancer.

BACKGROUND: Spinal metastases from lung cancer could result in life-threatening consequences. Few studies report the prognostic factors and compare different treatments in patients with spinal metastases from lung cancer. METHODS: From 2005 to 2014, we retrospectively reviewed and studied 140 patients with spinal metastases from lung cancer according to different treatments. To estimate overall survival and identify prognostic factors for survival, the Kaplan-Meier method and Cox regression analysis were adopted. In addition, the Kaplan-Meier method was used to compare different treatments for overall survival. RESULTS: All patients in a conservative group and a percutaneous vertebroplasty group died at a median survival time of 7 months for both groups. As for patients in the open-surgery group, 42 patients died at a median of 11 months, and 7 patients who were still alive at the time of this study were followed for a median of 29 months. Multivariate analysis suggested that better survival was significantly associated with American Spinal Injury Association grade D/E on admission, American Spinal Injury Association grade E after surgery, Eastern Cooperative Oncology Group performance status 1-2, and adjuvant radiation therapy in all 3 groups. In addition, Kaplan-Meier analysis showed that the overall survival rate of the open-surgery group (14.3%) was better than that of conservative group (0%) and the percutaneous vertebroplasty group (0%). CONCLUSIONS: A better overall survival outcome might be achieved by a series of comprehensive and individualized treatments and personalized treatment.