The mechanism of VCP-mediated metastasis of osteosarcoma based on cell autophagy and the EMT pathway

Objective Study of the molecular mechanisms of metastasis is still the research focus for osteosarcoma (OS) prevention. This study investigates the mechanism of valosin-containing protein (VCP) promoting OS metastasis in vitro through autophagy and epithelial–mesenchymal transition (EMT). Methods Different cell lines of osteosarcoma (143B and MG63) were adopted in this study. The level of VCP expression in osteosarcoma cells was changed, and the level of autophagy and the progression of the epithelial–mesenchymal transition (EMT) were observed. Then autophagy and EMT in OS cells were changed artificially, and proliferation and migration ability were observed. Results The expression of LC3II/I was decreased, but the insolubilized P62 protein expression was increased in the VCP inhibiting group and the autophagy inhibitor treatment group. Simultaneously, E-cadherin protein expression increased while N-cadherin protein expression decreased in the VCP inhibiting group but increased in the TGF-β1 treatment group. In addition, suppressing VCP can cause a decrease in Transforming Growth Factor β1 (TGF-β1), smad2, smad3, phosphorylated smad2 (p-smad2), and phosphorylated smad3 (p-smad3). Autophagy inhibitors and agonists have no significant effect on the migration and invasion of OS cells but can significantly affect the ability of cells to resist anoikis. EMT inhibitors and agonists have a proportional effect on the migration and invasion of OS cells. Conclusion VCP is likely to promote the migration and invasion of OS cells by inducing EMT, possibly via TGF-β1/smad2/3 signaling pathway. In this process, VCP-mediated autophagy may contribute to successful distant metastasis of tumor cells indirectly (AU)

The mechanism of VCP-mediated metastasis of osteosarcoma based on cell autophagy and the EMT pathway.

OBJECTIVE: Study of the molecular mechanisms of metastasis is still the research focus for osteosarcoma (OS) prevention. This study investigates the mechanism of valosin-containing protein (VCP) promoting OS metastasis in vitro through autophagy and epithelial-mesenchymal transition (EMT). METHODS: Different cell lines of osteosarcoma (143B and MG63) were adopted in this study. The level of VCP expression in osteosarcoma cells was changed, and the level of autophagy and the progression of the epithelial-mesenchymal transition (EMT) were observed. Then autophagy and EMT in OS cells were changed artificially, and proliferation and migration ability were observed. RESULTS: The expression of LC3II/I was decreased, but the insolubilized P62 protein expression was increased in the VCP inhibiting group and the autophagy inhibitor treatment group. Simultaneously, E-cadherin protein expression increased while N-cadherin protein expression decreased in the VCP inhibiting group but increased in the TGF-ß1 treatment group. In addition, suppressing VCP can cause a decrease in Transforming Growth Factor ß1 (TGF-ß1), smad2, smad3, phosphorylated smad2 (p-smad2), and phosphorylated smad3 (p-smad3). Autophagy inhibitors and agonists have no significant effect on the migration and invasion of OS cells but can significantly affect the ability of cells to resist anoikis. EMT inhibitors and agonists have a proportional effect on the migration and invasion of OS cells. CONCLUSION: VCP is likely to promote the migration and invasion of OS cells by inducing EMT, possibly via TGF-ß1/smad2/3 signaling pathway. In this process, VCP-mediated autophagy may contribute to successful distant metastasis of tumor cells indirectly.

The role of routine laboratory tests after unilateral total knee arthroplasty.

BACKGROUND: Recent studies suggest that routine laboratory tests are not required within 1 day after partial knee arthroplasty. In this study, we evaluated the utility of routine postoperative laboratory tests after initial unilateral total knee arthroplasty (TKA) in an Asian population. In addition, we explored risk factors associated with abnormal test results. METHODS: Clinical data of patients who underwent original unilateral TKA between 2015 and 2020 were retrospectively analyzed. Patient characteristics and laboratory test results were recorded. Multivariate binary logistic regression analysis was performed to identify risk factors associated with 3 abnormal laboratory results. RESULTS: A total of 713 patients, who underwent relevant laboratory tests within 3 days of TKA surgery, were enrolled. Among them, 8.1%, 9.9%, and 3.4% patients with anemia, hypoalbuminemia, and abnormal serum potassium levels required clinical intervention after surgery. Binary logistic regression analysis revealed that preoperative hemoglobin levels, estimated blood loss, and age were independent risk factors of postoperative blood transfusion in TKA patients. On the other hand, preoperative albumin levels, intraoperative blood loss, and operation time were risk factors associated with postoperative albumin supplementation. In addition, lower body mass index (BMI) and preoperative hypokalemia were potential risk factors of postoperative potassium supplementation. CONCLUSION: Considering that more than 90% of abnormal postoperative laboratory tests do not require clinical intervention, we believe that routine laboratory tests after surgery have little significance in patients with primary unilateral TKA. However, postoperative laboratory testing is necessary for patients with established risk factors.

Valosin-containing protein promotes metastasis of osteosarcoma through autophagy induction and anoikis inhibition via the ERK/NF-κß/beclin-1 signaling pathway.

Valosin-containing protein (VCP) promotes the development of metastasis in osteosarcoma (OS) via the PI3K/Akt signaling pathway. However, inhibition of the PI3K/Akt pathway does not completely reverse VCP-mediated invasion and migration of OS, suggesting that VCP-mediated OS invasion and migration involves additional mechanisms. In the present study, a positive correlation between the expression of VCP and cell autophagy was observed among OS tissues. Inhibiting VCP may decrease the survival of malignant cells; however, an autophagy stimulator may compensate for VCP inhibition and promote malignant cell survival. Altering the level of autophagy did not affect cell invasiveness or migration. ERK, NF-κß and beclin-1 protein expression levels were markedly decreased following VCP inhibition. These findings indicated that VCP may induce autophagy and enhance anoikis resistance without affecting cell invasiveness or migration. Via anoikis resistance, VCP may promote metastasis in OS. Therefore, targeting of the ERK/NF-κß/beclin-1 signaling pathway may be an effective therapeutic strategy for the management of OS.

Incidence and Risk Factors of Pressure Injuries in Surgical Spinal Patients: A Retrospective Study.

PURPOSE: The purpose of this study was to measure the incidence and identify risk factors of pressure injury development during the perioperative period in patients undergoing spinal surgery requiring intraoperative positioning in the prone position. DESIGN: Review of medical records. SUBJECTS AND SETTING: The sample comprised 3834 patients; 52.2% (n = 2006) were male and 65.5% (n = 2516) were older than 60 years. Most patients underwent surgery of the lumbosacral spinal segments (43.4%, n = 1667) followed by cervical (32.3%, n = 1241) and thoracic spinal segments (24.2%, n = 932). The study setting was the First Affiliated Hospital of Nanchang University, Jiang XI Province in southeastern China. METHODS: We reviewed charts of patients who underwent spinal surgery requiring intraoperative positioning in the prone position from November 2013 to July 2016. Demographic data, Braden Scale for Pressure Sore Risk cumulative score (measured before preoperative transport), body mass index (BMI), duration of surgery, preoperative time (time between preoperative transport from the inpatient unit to when the operation began), postoperative time (time between when the operation was over and postoperative transport to the inpatient unit), and development of any pressure injury were collected using a standardized form. Factors associated with an increased or decreased likelihood of pressure injury were initially evaluated with χ and independent t tests. Logistic regression was then used to identify potential risk factors for perioperative pressure injury in patients undergoing open spinal surgery requiring placement in the supine position during surgery. RESULTS: One hundred eighty-four of 3840 patients (4.7%) developed pressure injuries. Multivariate analysis indicated that factors associated with intraoperative pressure injury development were older than 60 years (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.02-2.17), BMI under 18 kg/m (OR = 2.45, 95% CI = 4.05-5.21), cumulative Braden Scale score 13 or less (OR = 6.59, CI = 2.23-3.98), prolonged preoperative time (OR = 5.99, 95% CI = 3.21-6.12), and prolonged postoperative time (OR = 14.23, 95% CI = 10.23-21.19). CONCLUSIONS: Based on these findings we recommend extending preventive interventions for pressure injury to incorporate the time from preoperative transport to the surgical suite to inpatient care unit following surgery.

Blocking fatty acid synthase inhibits tumor progression of human osteosarcoma by regulating the human epidermal growth factor receptor 2/phosphoinositide 3-kinase/protein kinase B signaling pathway in xenograft models.

Previous studies have demonstrated that fatty acid synthase (FASN) is overexpressed in osteosarcoma (OS) cells and tissues and, therefore, knockdown of FASN may inhibit OS cell proliferation, migration and invasion via regulation of the human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K)/protein kinase B(Akt) signaling pathway in vitro. However, the tumor microenvironment has a crucial role in the determination of tumor malignant phenotype. The aim of the present study was to investigate the effect of knockdown of FASN on OS progression and the potential molecular mechanism in nude mice with orthotopic tumor implants in vivo. Results demonstrated that the knockdown of FASN markedly suppressed the growth and metastasis of OS, at least partially, by blocking the HER2/PI3K/Akt signal pathway in mice with intratibial 143B OS xenografts. These results suggest that the FASN/HER2/PI3K/Akt signaling pathway may be a potential therapeutic target for OS management.

A New Entrance Technique for C2 Pedicle Screw Placement and the Use in Patients With Atlantoaxial Instability.

STUDY DESIGN: A prospective study and a technique note. OBJECTIVES: To introduce a new entrance technique for C2 pedicle screw placement and to measure the related linear and angular parameters about the entrance point on computed tomography (CT) images. The safety of this technique for patients with atlantoaxial instability was also evaluated. BACKGROUND DATA: Although earlier studies have introduced different methods for C2 pedicle screw placement, the entry points and the angular parameters may be variable. Few studies have established a fixed entry point on the basis of the anatomic structure of C2 for pedicle screw placement. METHODS: A total of 60 dry C2 vertebrae were obtained for anatomic measurement in the study. The posterior bilateral nutrient foramens of C2 lamina were selected as the entry points for pedicle screw placement. The foramens were marked with needles and then the vertebrae underwent CT scan. The axial and sagittal planes of C2 pedicles were harvested and 4 linear and 2 angular parameters about the entry point were determined. After that, we used the entrance technique on 31 patients with atlantoaxial instability in a prospective study. CT of the cervical spine was performed to evaluate the safety of the entrance technique. RESULTS: The nutrient foramens exist in 97% of the left lamina and 93% of the right lamina of the C2 vertebra. The overall mean distance from the entry point (nutrient foramen) to the superior border of lamina (PSD), to the inferior border of lamina (PID), to the medial border of the pedicle (PMD), and the length of pedicle screw trajectory (PL, transit the pedicle center) were 3.32±0.63, 8.33±1.21, 6.85±1.00, and 24.47±1.51, respectively. The averaged transverse angle (α) on the axial plane and the superior angle (ß) on the sagittal plane were 19.83±3.83 and 30.12±6.02 degrees, respectively. Then, 31 patients underwent bilateral C2 pedicle screw fixation without screw violation into the spinal canal or vertebral artery injury by the new entrance technique. The overall mean angles α and ß and the length of the pedicle screw were 17.52±3.81 and 34.29±4.18 degrees and 25.85±2.06 mm, respectively. No statistical differences were found in these 3 parameters between the dry C2 vertebrae and the C2 vertebrae of patients who underwent the surgery (P>0.05). CONCLUSIONS: Using the posterior bilateral nutrient foramens of the C2 lamina as the entry point is a helpful intraoperative landmark for C2 pedicle screw placement.

Radiographic Evaluation of the Reliability of Neck Anatomic Structures as Anterior Cervical Surgical Landmarks.

BACKGROUND: Accurate location of the skin incision is helpful to decrease the technical difficulty and save the operative time in anterior cervical spine surgery. Spine surgeons usually use the traditional neck anatomic structures (the hyoid bone, thyroid cartilage, and cricoid cartilage) as landmarks during the surgery. However, the reliability of these landmarks has not been validated in actual practice. OBJECTIVE: To find out which landmark is the most accurate for identifying the cervical levels in anterior cervical spine surgery. METHODS: The lateral flexion and extension radiographs of cervical spine in standing position from 30 consecutive patients from January 2015 to February 2015 were obtained. The cervical vertebral bodies from C2 to C7 were divided equally into 2 segments. The cervical segments corresponding to each of the surface landmarks were recorded on the flexion and extension radiographs, respectively, and the displacement of corresponding cervical segments from the flexion to extension radiographs for each landmark was calculated. RESULTS: Based on the measurements, the main corresponding cervical levels for the mandibular angle were C2 on both of the flexion and extension films, for the hyoid bone were the C3-C4 interspace on flexion film and C3 on extension film, for the thyroid cartilage C5 on both of flexion and extension films, and for the cricoid cartilage C6 on flexion film and C5-C6 interspace on extension film, respectively. The ratios of displacement within 2 segments from flexion to extension were 83.3% (25/30) for mandibular angle, 56.7% (17/30) for hyoid bone, 66.7% (20/30) for thyroid cartilage, and 56.7% (17/30) for cricoid cartilage, respectively. The mean displacement from flexion to extension films were significantly less than 2 cervical segments for the mandibular angle but greater than 2 segments for the other landmarks. Significant differences were found between mandibular angle and the other 3 landmarks for the displacement from flexion to extension. CONCLUSIONS: The angle of mandible was found to be the most accurate landmark for identifying the cervical level, which corresponded to C2 and C2-C3 disc space. The hyoid bone, thyroid cartilage, and cricoid cartilage were not reliable to predict the cervical levels.

A comparison of local bone graft with PEEK cage versus iliac bone graft used in anterior cervical discectomy and fusion.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is a popular procedure for patients with cervical spondylotic myelopathy, but few studies reported the clinical outcomes of cervical local bone graft with a PEEK cage used in it. This retrospective study was performed to compare the clinical and radiological outcomes of using local bone graft with a PEEK cage versus iliac bone graft in ACDF. PATIENTS AND METHODS: A total of 60 consecutive patients who underwent ACDF were evaluated from January 2010 to January 2013. Twenty-nine patients received ACDF with a PEEK cage combined with cervical local bone graft (local bone group) and 31 patients received ACDF with autologous tricortical iliac bone graft (iliac bone group). The intraoperative and perioperative complications of both groups were recorded. Preoperative and postoperative radiographs were taken to calculate the ratio of interbody height to the disc height and the interbody bony fusion rate. The Japanese Orthopedic Association (JOA) score and visual analogue scale (VAS) were used to estimate postoperative clinical outcomes. RESULTS: The mean follow-up duration was 25.0±3.8months in the local bone group and 24.4±3.4months in the iliac bone group (P=0.56). Although there was no significant difference between the two groups in terms of blood loss (P=0.17), the length of surgery was significantly less in the local bone group comparing with that of iliac bone group (P=0.01). Postoperatively, VAS scores were significantly decreased, and JOA scores were improved in both groups. However, no statistically significant differences were found between the two groups at final follow up (P=0.45 and P=0.93). The disc space height and segmental interbody angle at the surgical segment were greater in local bone group than those in the iliac bone group (P<0.001 and P<0.001). The fusion rates were 93.1% in local bone group and 90.3% in the iliac bone group at last follow up (P=0.70). Perioperative complication rates in local bone group and iliac bone groups were 6.8% and 29%, respectively (P=0.04). CONCLUSIONS: Based on this study, patients receiving ACDF with local bone graft combined with a PEEK cage had significant shorter operation time, lower perioperative complications rate, and better radiological results comparing with those with an iliac bone graft alone. It seems that the local bone graft with a PEEK cage appears to be a safe alternative to the iliac bone graft for ACDF.

AMD3100 inhibits the migration and differentiation of neural stem cells after spinal cord injury.

It was reported that CXCR4 signaling played an important role in the migration and differentiation of endogenous neural stem cells after spinal cord injury (SCI). However, the molecular mechanism of it is still unclear. Here, we established a model of SCI in rats and AMD3100 was used to treat them. The rats were then sacrificed and the injured spinal cord specimens were harvested. Additionally, the neural stem cells (NSCs) line was culture and treated with AMD3100 in vitro. Results showed the locomotor function of SCI rats was worse after treated with AMD3100. And the expression levels of Nestion in neural stem cells and ß-tubulin in neuron cells were significantly increased in the injured spinal cord, which can be inhibited by the CXCR4 antagonist of AMD3100. Additionally, the expression of ß-catenin and phosphorylase ß-catenin protein was significantly down regulated by AMD3100. In vitro, the NSCs proliferation ability was inhibited and the migration was decreased after treated with AMD3100. Also, the expression of Nestion, ß-tubulin, ß-catenin and phosphorylase ß-catenin protein was significantly decreased in AMD3100 group comparing with untreated group. Taken together, this study suggested that AMD3100 could inhibit the migration and differentiation of endogenous neural stem cells in rats with SCI. The mechanism of it maybe that AMD3100 could down regulate of SDF-1/CXCR4 by targeting ß-catenin signaling pathway.

One-stage posterior surgical management of lumbosacral spinal tuberculosis with nonstructural autograft.

OBJECTIVE: Lumbosacral spinal tuberculosis is rare in current population. Previous studies have reported effective outcomes about anterior, antero-posterior and posterior surgery for treating tuberculosis of lumbosacral region. However, the bone grafts used in these studies are mainly structural bone and mesh cage. The purpose of this study is to evaluate the efficacy and safety of nonstructural autograft in the surgical treatment of lumbosacral tuberculosis by one-stage posterior procedure. PATIENTS AND METHODS: A total of 21 patients with lumbosacral tuberculosis were retrospectively reviewed between January 2012 and December 2014. All the patients underwent one-stage posterior debridement, interbody fusion with nonstructural autograft and posterior instrumentation. The preoperative and postoperative erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) and visual analogue scale (VAS) were recorded. Preoperative and postoperative lumbosacral angle and intervertebral space height were measured on the plain films. American Spinal Injury Association (ASIA) Impairment Scale was used to evaluate the neurological outcomes of the patients. RESULTS: The average follow up period was 22.9±6.7months (range 12-36 months). The preoperative ESR and CRP were 33.4±10.5mm/h and 30.3±20.3mg/l, respectively, which decreased to 15.2±7.1mm/h and 10.6±5.8mg/l postoperatively with significant differences (P<0.05). The lumbosacral angles and intervertebral space height were increased from preoperative 20.4°±4.5° and 9.7±1.9mm to postoperative 25.6°±4.6° and 12.3±2.1mm, respectively (P<0.001 and P<0.001). At the final follow up, a loss of 2.1°of lumbosacral angles and 1.6mm of intervertebral space height was observed. The VAS scores were decreased from 4.73 to 2.71. Bony fusion was achieved in all patients at 6 months after surgery. Neurological outcomes were improved with 1-2 grades in most of the patients. One patient got wound infection and was cured by daily dressing. Complications related to instrumentation or neurological deficit weren't observed. CONCLUSION: Combined with one-stage posterior debridement and instrumentation, interbody fusion with nonstructural autograft is an effective option for lumbosacral tuberculosis.

HELQ reverses the malignant phenotype of osteosarcoma cells via CHK1-RAD51 signaling pathway.

HELQ is a DNA helicase important for repair of DNA lesions and has been linked to several types of cancer. However, little is known about its relationship with osteosarcoma (OS) and its mechanism. In the present study, the expression of HELQ and its downstream mediators in OS cells was assayed by quantitative PCR and western blot analysis. The function of HELQ in OS cells was investigated by Transwell invasion, wound healing, CCK8 assays and Comet assay. The results demonstrated that HELQ gene and protein were expressed in OS cells. OS cell invasion, migration, proliferation and DNA damage repair were enhanced by HELQ knock-down with shRNA-lentivirus and inhibited by HELQ overexpression with lentivirus transfection. Furthermore, the antitumor activities of HELQ may be associated with upregulated expression of the DNA damage-related proteins CHK1 and RAD51. Our findings indicated that HELQ confers an anti-invasive phenotype on OS cells by activating the CHK1-RAD51 signaling pathway and suggested that HELQ could be recognized as a promising therapeutic target for OS and other types of malignant tumors.

Transcription factor NF­YA promotes a malignant phenotype by upregulating fatty acid synthase expression.

Recent studies have revealed that increased expression of the alpha subunit of nuclear transcription factor Y (NF­YA) is associated with the malignant phenotype of various tumors. However, whether elevated expression of NF­YA promotes a malignant phenotype in osteosarcoma (OS), and the molecular mechanisms underlying this predicted effect is currently unknown. In the present study, small hairpin RNA (shRNA)­mediated knockdown of endogenous NF­YA significantly inhibited the migration and invasion capabilities of OS cells in vitro, whereas ectopic expression of NF­YA increased the migration and invasion capabilities of these cells. In addition, the induction of upregulated NF­YA expression on the malignant phenotype of OS cells was attenuated by silencing fatty acid synthase (FASN) expression. Furthermore, the expression level of FASN was increased by upregulating NF­YA, while decreased FASN expression was observed following NF­YA silencing in OS cells. The results of the present study suggest that NF­YA may promote a malignant phenotype in OS cells, in part, by activating the FASN signaling pathway, which may represent a promising target for the management of OS.

Is nonstructural bone graft useful in surgical treatment of lumbar spinal tuberculosis?: A retrospective case-control study.

Surgical intervention is an important option for treating spinal tuberculosis. Previous studies have reported different surgical procedures and bone grafts for it. To our knowledge, few studies demonstrated the clinical results of using nonstructural autogenous bone graft in surgical treatment of spinal tuberculosis.The purpose of this study is to compare the clinical outcomes of surgical management lumbar spinal tuberculosis by one-stage posterior debridement with nonstructural autogenous bone grafting and instrumentation versus anterior debridement, strut bone grafting combined with posterior instrumentation.A total of 58 consecutive patients who underwent surgical treatment due to lumbar spinal tuberculosis from January 2011 to December 2013 were included. A total of 22 patients underwent one-stage posterior debridement, nonstructural autogenous bone grafting, and instrumentation (group A), and 36 patients received anterior debridement, strut bone grafting combined with posterior instrumentation (group B). The operative duration, total blood loss, perioperative transfusion, length of hospital stay, hospitalization cost, and complications were recorded. The bony fusion of the graft was assessed by computed tomography scans. American Spinal Injury Association (ASIA) Impairment Scale was used to evaluate the neurological function of patients in the 2 groups.All the patients were followed up, with a mean follow-up duration of 21.6 ±â€Š5.7 months in group A and 22.3 ±â€Š6.2 months in group B (P = 0.47). The average operative duration was 257.5 ±â€Š91.1 minutes in group A and 335.7 ±â€Š91.0 minutes in group B (P = 0.002). The mean total blood loss was 769.6 ±â€Š150.9 mL in group A and 1048.6 ±â€Š556.9 mL in group B (P = 0.007). Also, significant differences were found between the 2 groups in perioperative transfusion volumes, length of hospital stay, and hospitalization cost (P < 0.05), which were less in group A compared with group B. Patients with ASIA grade C/D in the 2 groups were improved with 1 to 2 grades after the surgery with no statistical difference (P = 1.000). The perioperative complications rate was 9.1% (2/22) in group A and 13.9% (5/36) in group B (P = 0.897).Based on a retrospective study, the procedure of one-stage posterior debridement, nonstructural autogenous bone grafting, and instrumentation has a significant shorter operative duration, lower blood loss and perioperative transfusion, shorter hospital stay, and less hospitalization cost compared with the one of anterior debridement, strut bone grafting combined with posterior instrumentation for treating lumber spinal tuberculosis.

Is Urgent Decompression Superior to Delayed Surgery for Traumatic Spinal Cord Injury? A Meta-Analysis.

BACKGROUND: Traumatic spinal cord injury (SCI) is a common disease in current clinical practice. Previous studies have reported that early surgical decompression was better to improve neurologic outcomes than that of late surgery. However, most of the studies set early surgery within 72 hours. Is urgent surgery within 24 hours superior to late surgery for SCI? It remains controversial. OBJECTIVE: To determine whether neurologic outcomes of SCI in patients who underwent early surgery (<24 hours after injury) are better than those who underwent late surgery (≥ 24 hours after injury) by meta-analysis. METHODS: Electronic databases such as PubMed, MEDLINE, EMBASE, and Cochrane library were selected to detect the potentially related trials up to June 2015 that compared the outcomes of early surgery (<24 hours after injury) versus late surgery (≥ 24 hours after injury) for the treatment of traumatic SCI. Data extraction and quality assessment were according to Cochrane Collaboration guidelines. Outcome evaluations were total motor score, neurologic improvement rate, length of hospital stay and intensive care unit (ICU) stay, complications, and mortality. Results were expressed as odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence interval (CI). RESULTS: Nine articles comparing 2 cohorts that had early and late surgery for SCI were identified in this study. Statistically, there were significant differences between early and late surgery in total motor score (MD = 3.30, 95% CI = 0.82 ∼ 5.79, P < 0.01), neurologic improvement rate (OR = 1.66, 95% CI = 1.19 ∼ 2.31, P < 0.01), length of hospital stay (MD = -4.76, 95% CI = -9.19 ∼ -0.32, P = 0.04), and complications (OR = 0.61, 95% CI = 0.40 ∼ 0.91, P = 0.02). However, no significant differences were found between the 2 groups in mortality (OR = 1.39, 95% CI = 0.51 ∼ 3.75, P = 0.52). Two studies showed fewer ICU stays in the early-surgery group than in the late group. CONCLUSIONS: On the basis of this meta-analysis, urgent surgery within 24 hours for SCI significantly improved the neurologic outcomes compared with late surgery. It is suggested that urgent decompression within 24 hours is superior to delayed surgery for SCI.

Hybrid Decompression Technique Versus Anterior Cervical Corpectomy and Fusion for Treating Multilevel Cervical Spondylotic Myelopathy: Which One Is Better?

BACKGROUND: The hybrid decompression technique (corpectomy combined with discectomy) and anterior cervical corpectomy with fusion (ACCF) both provide good neurological recovery and disease stabilization for the treatment of multilevel cervical spondylotic myelopathy (CSM). However, no single study has been large enough to determine definitively which one is superior for this condition. OBJECTIVE: A meta-analysis was conducted to compare the clinical efficacy and safety of the hybrid decompression technique versus ACCF for the treatment of multilevel CSM. METHODS: Electronic databases such as PubMed, MEDLINE, EMBASE, Google Scholar, and the Cochrane Library were selected to search for potentially relevant trials up to April 2015 that compared the outcomes of the hybrid technique with ACCF for the treatment of multilevel CSM. Data extraction and quality assessment were performed according to Cochrane Collaboration guidelines. The outcome assessments were duration of surgery, blood loss, Cobb angle of C2-C7, segment angle, fusion rate, Japanese Orthopedics Association score, Neck Disability Index, and complications. The results were expressed as the odds ratio (OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with a 95% confidence interval (CI). RESULTS: Five controlled clinical trials published between 2009 and 2013, involving 356 patients (hybrid, 196; ACCF, 160) with 3- or 4-level CSM were retrieved in this study. Overall, there were significant differences between the 2 treatment groups for blood loss (MD = -38.69, 95% CI = -54.62 to -22.76, P < 0.01), fusion rate (OR = 2.56, 95% CI = 1.11 to 5.93, P = 0.03), and complications (OR = 0.25, 95% CI = 0.15 to 0.43, P < 0.01). However, no significant differences were found for duration of surgery (MD = -4.50, 95% CI = -22.902 to 13.91, P = 0.63), Cobb angle of C2-C7 after surgery (MD = 3.32, 95% CI = -3.72 to 10.37, P = 0.35), segment angle after surgery (MD = 2.87, 95% CI = -2.47 to 8.21, P = 0.29), Japanese Orthopedics Association score (MD = -0.07, 95% CI = -0.36 to 0.22, P = 0.62), or Neck Disability Index (MD = -0.86, 95% CI = -3.26 to 1.54, P = 0.48). CONCLUSION: Based on this meta-analysis, both the hybrid technique and ACCF can achieve good results for CSM. However, the hybrid technique is associated with significantly less blood loss, complications, and a higher fusion rate than ACCF.

Let-7i inhibits the malignant phenotype of osteosarcoma cells by targeting Aurora-B.

Our previous study indicated that Aurora-B is involved in osteosarcoma (OS) cell invasion and metastasis; however, the mechanism underlying Aurora-B overexpression in OS remains unknown. In the present study, significantly downregulated let-7i expression in OS tissues and OS cells was observed compared with that in normal adjacent tumorous tissues and human osteoblast cell lines. Bioinformatic predictions have revealed a conserved binding site in a microRNA locus on Aurora­B, suggesting the potential of let­7i targeting the Aurora­B gene. To validate this, a luciferase reporter assay was performed on OS cells. The results indicated that Aurora­B is a likely to be a direct target negatively regulated by let­7i. The expression of let­7i in OS cells was restored by infection with let­7i mimics. Results revealed that Aurora­B mRNA and protein expression levels were significantly decreased. Furthermore, the proliferation, migration and invasion abilities of OS cells were significantly suppressed by infection with let­7i mimics. Notably, the inhibitory effect of silencing Aurora­B by LV­shAurora­B on cell proliferation, migratory and invasive ability was significantly lower than that by let­7i mimics, which indicated that let­7i inhibits cell malignant phenotypes partially by targeting Aurora­B in OS cells. All data suggested that let­7i may be a novel potential target for OS treatment.

Knockdown of Aurora-B alters osteosarcoma cell malignant phenotype via decreasing phosphorylation of VCP and NF-κB signaling.

The aim of this study is to investigate the effects of inhibiting Aurora-B on osteosarcoma (OS) cell malignant phenotype, phosphorylation of valosin-containing protein (VCP), and the activity of NF-κB signaling in vitro. The expressions of Aurora-B and p-VCP proteins were detected by immunohistochemistry in 24 OS tissues, and the relationship between Aurora-B and p-VCP was investigated. The results showed that there was a positive correlation between Aurora-B and p-VCP proteins. The expression of Aurora-B in human OS cell lines U2-OS and HOS cells was inhibited by specific short hairpin RNA (shRNA) lentivirus (AURKB-shRNA lentivirus, Lv-shAURKB) which targeted Aurora-B. The results showed that the phosphorylation of VCP, the activity of NF-κB signaling pathway and the malignant phenotype of OS cells were all suppressed by knockdown of Aurora-B. It indicated that the inhibition of Aurora-B alters OS cells malignant phenotype by downregulating phosphorylation of VCP and activating of the NF-κB signaling pathway in vitro.

Demethylation-mediated miR-129-5p up-regulation inhibits malignant phenotype of osteogenic osteosarcoma by targeting Homo sapiens valosin-containing protein (VCP).

Previous studies demonstrated that increased Homo sapiens valosin-containing protein (VCP) may be involved in osteosarcoma (OS) metastasis. However, the underlying mechanism of VCP over-expression in OS remains unknown. In the present study, we found a significantly negative correlation between miR-129-5p and VCP protein expression in OS tissues with pulmonary metastasis (Spearman's rho, rs = -0.948). Bioinformatical prediction, Luciferase reporter assay, Western blot, and RT-PCR assays performed on OS cells indicated that VCP is a target of miR-129-5p. In addition, three CPG islands in the region of miR-129-5p promoter were detected by bioinformatical prediction, and significantly higher expression of miR-129-5p and lower methylation level of miR-129-2 gene in OS cells treated with 5-Aza-2'-deoxycytidine (a potent DNA demethylating agent) than in those untreated cells were observed. Furthermore, lower migratory and invasive ability was found in cells with elevated miR-129-5p than in those with decreased miR-129-5p. These findings indicated that increased miR-129-5p may be mediated by demethylation and inhibit OS cell migration and invasion by targeting VCP in OS, and targeting miR-129-5p/VCP signaling pathway may serve as a therapeutic strategy for OS management, although further studies will be necessary.