Effects of "fixation-fusion" sequence of lumbar surgery on surgical outcomes for patients with lumbar spinal stenosis: study protocol for a multicenter randomized controlled trial.

BACKGROUND: New-onset neurological symptoms such as numbness and pain in lower extremities might appear immediately after conventional lumbar interbody fusion (LIF) surgery performed in patients with lumbar spinal stenosis. METHODS AND ANALYSIS: This is a multicenter, randomized, open-label, parallel-group, active-controlled trial investigating the clinical outcomes of modified LIF sequence versus conventional LIF sequence in treating patients with lumbar spinal stenosis. A total of 254 eligible patients will be enrolled and randomized in a 1:1 ratio to either modified LIF sequence or conventional LIF sequence group. The primary outcome measure is the perioperative incidence of new-onset lower extremity neurological symptoms, including new adverse events of pain, numbness, and foot drop of any severity. Important secondary endpoints include visual analogue scale (VAS) pain score and lumbar Japanese Orthopaedic Association (JOA) recovery rate. Other safety endpoints will also be evaluated. The safety set used for safety data analysis by the actual surgical treatment received and the full analysis set for baseline and efficacy data analyses according to the intent-to-treat principle will be established as the two analysis populations in the study. CONCLUSION: This study is designed to investigate the clinical outcomes of modified LIF sequences in patients with lumbar spinal stenosis. It aims to provide clinical evidence that the modified "fixation-fusion" sequence of LIF surgery is effective in treating lumbar spinal stenosis. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx ID: ChiCTR2100048507.

[Application of "Zoning Method" foraminotomy in posterior cervical endoscopic surgery].

OBJECTIVE: To explore the safety, effectiveness and consistency of "Zoning Method" foraminotomy in posterior cervical endoscopic surgery. METHODS: From March 2016 to October 2018, 21 patients with cervical spondylotic radiculopathy were enrolled. Endoscopic foraminotomy and nucleus pulposus enucleation were performed in the patients. There were 13 males and 8 females, aged from 35 to 56 years old with an average of (47.3±5.1) years. The surgical segment of 6 cases were C4,5, 10 cases were C5,6 and 5 cases were C6,7. The "Zoning Method" was proposed and used to complete the foraminotomy under endoscope, and then to perform nucleus pulposus removal and nerve root decompression. The operation length, intraoperative bleeding volume and complications were recorded, and NDI, VAS were evaluated before operation, 1 day after the operation and 1 week after the operation. RESULTS: All the operations were successful. The operation length was(46.10±26.39) min, intraoperative bleeding volume was (50.10±18.25) ml, and there were no complications such as nerve injury, dural tear or vertebral artery injury. All 21 patients were followed up for 3 to 9 months, with a median of 6 months. Postoperative VAS and NDI were obvious improved (P<0.05);there was significant difference in VAS between postoperative 1 d and 1 week(P<0.05);and there was no significant difference in NDI between postoperative 1 d and 1 week (P>0.05). CONCLUSION: Endoscopic foraminotomy with "Zoning Method" is safe clinically significant, and consistent.

MiR-499a-5p suppresses apoptosis of human nucleus pulposus cells and degradation of their extracellular matrix by targeting SOX4.

Emerging evidence suggests that microRNAs (miRNAs, miRs) play important roles in the development of intervertebral disc degeneration (IVDD). Nonetheless, the expression level and biological function of miR-499a-5p in IVDD are still unclear. In this study, we found that miR-499a-5p was significantly downregulated in degenerative tissues of the human nucleus pulposus (NP) compared with healthy tissues. Knockdown of miR-499a-5p promoted NP cell (NPC) apoptosis, stimulated caspase activation, enhanced MMP3 and MMP13 expression, and downregulated aggrecan and type II collagen. Furthermore, TNF-α-treated NPCs showed increased apoptosis and induced an imbalance between anabolism and catabolism of the extracellular matrix (ECM); these changes were attenuated by miR-499a-5p overexpression. Research into possible mechanisms revealed that miR-499a-5p suppressed the expression of SOX4 both at mRNA and protein levels and directly bound to the 3' untranslated region of SOX4 mRNA. Ectopic expression of SOX4 attenuated the negative effect of miR-499a-5p on NPC apoptosis and the positive effect on ECM synthesis. Taken together, these results indicate that miR-499a-5p may attenuate TNF-α-induced NPC apoptosis and an imbalance between anabolism and catabolism of the ECM by downregulating SOX4.

TRIM14 regulates cell proliferation and invasion in osteosarcoma via promotion of the AKT signaling pathway.

Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family serve as important regulators of tumorigenesis. However, the biological role of TRIM14 in osteosarcoma remains to be established. In this study, we showed that TRIM14 is upregulated in human osteosarcoma specimens and cell lines, and correlated with osteosarcoma progression and shorter patient survival times. Functional studies demonstrated that overexpression of TRIM14 enhances osteosarcoma cell proliferation, clone formation, cell cycle procession, migration and invasion in vitro and promotes tumor growth in vivo, and conversely, its silencing has the opposite effects. Furthermore, TRIM14 overexpression induced activation of the AKT pathway. Inhibition of AKT expression reversed the TRIM14-mediated promotory effects on cell growth and mobility, in addition to TRIM14-induced epithelial-to-mesenchymal transition (EMT) and cyclin D1 upregulation. Our findings collectively suggest that TRIM14 functions as an oncogene by upregulating the AKT signaling pathway in osteosarcoma cells, supporting its potential utility as a therapeutic target for this disease.

MiR-101 Targets the EZH2/Wnt/ß-Catenin the Pathway to Promote the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.

Mounting evidence indicates that microRNAs (miRNAs) are involved in multiple processes of osteogenic differentiation. MicroRNA-101 (miR-101), identified as a tumor suppressor, has been implicated in the pathogenesis of several types of cancer. However, the expression of miR-101 and its roles in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) remain unclear. We found that the miR-101 expression level was significantly increased during the osteogenic differentiation of hBMSCs. MiR-101 depletion suppressed osteogenic differentiation, whereas the overexpression of miR-101 was sufficient to promote this process. We further demonstrated that enhancer of zeste homolog 2 (EZH2) was a target gene of miR-101. EZH2 overexpression and depletion reversed the promoting or suppressing effect of osteogenic differentiation of hBMSCs, respectively, caused by miR-101. In addition, we showed that miR-101 overexpression promoted the expression of Wnt genes, resulting in the activation of the Wnt/ß-catenin signaling pathway by targeting EZH2, while the activity of ß-catenin and the Wnt/ß-catenin signaling pathway was inhibited by ICG-001, a ß-Catenin inhibitor, which reversed the promoting effect of miR-101. Finally, miR-101 also promotes in vivo bone formation by hBMSCs. Collectively, these data suggest that miR-101 is induced by osteogenic stimuli and promotes osteogenic differentiation at least partly by targeting the EZH2/Wnt/ß-Catenin signaling pathway.

A report of a novel technique: The comprehensive fibular autograft with double metal locking plate fixation (cFALP) for refractory post-operative diaphyseal femur fracture non-union treatment.

INTRODUCTION: The refractory post-operative diaphyseal femur fracture (DFF) non-union is extremely difficult to treat and remains severe challenges for orthopedists. Although several traditional internal fixations and novel biomedical techniques have been used in managing this complication, its treatment is still fraught with severe challenges. PATIENTS AND METHODS: Starting from 1999, 5 patients after three previous internal fixation operations showing refractory DFF non-union underwent the comprehensive fibular autograft with double metal locking plates fixation (cFALP) surgery. The autogenous fibular was first harvested and non-evenly split into two halves in a longitudinal manner. After retracting all previous internal fixation(s), the larger half strut fibula was hammered into the femur canal while the smaller half was fragmented into small pieces and filled surrounding the DFF site. Two locking compression plate were fixed on the lateral and anterior (or antero-lateral) side of the femur, respectively. RESULTS: The follow-up ranged from 60 to 96 weeks. All cases (100%) achieved bony union without severe complications. The mean time to union was 36±14.7 weeks (range 24-60 weeks). CONCLUSION: The cFALP is a promising surgical modality for DFF non-union treatment. However, because fibular harvest may cause severe complications, the cFLAP should only be considered in refractory DFF non-union cases.

MicroRNA-320a Regulates the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Targeting HOXA10.

BACKGROUND/AIMS: Human bone marrow-derived mesenchymal stem cells (hMSCs) are a promising cell source for bone engineering owing to their high potential to differentiate into osteoblasts. The bone morphogenetic protein-inducible gene homeobox a10 (HOXA10) is a critical regulator of osteogenesis. The objective of the present study was to identify microR-NAs (miRNAs) targeting HOXA10 and examine the effects on the osteogenic differentiation of hMSCs. METHODS: Based on in silico analysis, HOXA10-targeting miRNAs were selected and their regulatory roles in osteoblast differentiation were investigated. RESULTS: Six HOXA10-targeting miRNAs were identifIed by computational analysis, of which miR-320a was selected for further analysis because it was downregulated during osteogenic induction. Overexpression of miR-320a downregulated HOXA10 and significantly inhibited osteogenesis in hMSCs, as determined by the downregulation of the osteogenic markers Runx2, ALP, and OC and the inhibition of ALP activity and matrix mineralization, whereas miR-320a inhibition had the opposite effects. Furthermore, ectopic expression of HOXA10 (not including 3'-UTR) rescued the effects of miR-320a on osteogenic differentiation. CONCLUSION: These results suggest that miR-320a acts as a critical regulator of osteogenic differentiation of hMSCs by repressing its target HOXA10.

Brown-Sequard syndrome associated with Horner syndrome following cervical disc herniation.

INTRODUCTION: Brown-Sequard syndrome (BSS) has been reported in patients with various spinal pathologies, including spinal traumatic injuries, spinal cord neoplasms, epidural hematomas and spinal cord ischemia. Pure BSS caused by cervical disc herniation is very rare. CASE PRESENTATION: We report a rare case of cervical disc herniation presenting as BSS associated with Horner syndrome (HS), which has not been reported up to now. A prompt diagnosis by magnetic resonance imaging (MRI), followed by spinal cord decompression was performed. A postoperative rapid improvement of the neurological deficits was observed. DISCUSSION: We review the literature and discuss the functional anatomy of spinal cord of BSS combined with HS. And it is important that clinicians be aware that a MRI of spinal cord is needed for those patients with a thoracic sensory level, and that a thoracic sensory level might not only depend on the level of spinal cord injury but also on the stage of evolution of the lesion.