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Background Kruppel like factor 10 (KLF10), which is also known as TGF-β Inducible Early Gene-1 (TIEG1), plays a crucial role in regulating cell proliferation, cell apoptosis and inflammatory reaction in human carcinoma cells. Moreover, KLF10 knockout in mice leads to severe defects associated with muscle, skeleton and heart etc. However, the function of KLF10 in intervertebral disc degeneration (IVDD) has not been reported yet. Methods The relationship between KLF10 and IVDD were investigated in nucleus pulposus (NP) tissues from human and rats. The role of KLF10 in NP cells was explored via loss or gain of function experiments. IVDD rat models were constructed through needle puncture and the effects of KLF10 in IVDD model of rats were investigated via intradiscal injection of KLF10. Results We first found that KLF10 was lowly expressed in degenerative NP tissues and the level of KLF10 showed negative correlation with the disc grades of IVDD patients. Loss or gain of function experiments demonstrated that KLF10 could inhibit apoptosis and enhance migration and proliferation of IL-1β induced NP cells. And KLF10 overexpression reduced extracellular matrix (ECM) degeneration and enhanced ECM synthesis, whereas knockdown of KLF10 resulted in adverse effects. These positive effects of KLF10 could be reversed by the inhibition of TGF-β signaling pathway. In vivo, KLF10 overexpression alleviated IVDD. Conclusions This is the first study to reveal that KLF10 was dysregulated in IVDD and overexpressed KLF10 could alleviate IVDD by regulating TGF-β signaling pathway both in vitro and in vivo, which were involved in prohibiting apoptosis, promoting proliferation and migration of NP cells. The translational potential of this article: Overexpression of KLF10 might be an effective therapeutic strategy in the treatment of IVDD.

Objectives Degenerative disc disease is characterized by an enhanced breakdown of its existing nucleus pulposus (NP) matrix due to the dysregulation of matrix enzymes and factors. Ubiquitin‐specific protease 15 (USP15) is reported to be abnormal in certain human diseases. However, its role in NP degeneration remains unclear. Therefore, we aimed to explore the function of USP15 in degenerative NP cell specimens. Methods We induced gene silencing and overexpression of USP15 in degenerative NP cells using RNA interference (RNAi) and a lentiviral vector, respectively. qRT‐PCR and Western blotting were used to determine gene and protein expression levels. Cell apoptosis was analysed via flow cytometry. Protein interaction was examined by performing a co‐immunoprecipitation assay. Furthermore, the PI3K inhibitor LY294002 and agonist IGF‐1 were used to investigate the link between USP15 and AKT in NP degeneration. Results We found that USP15 was up‐regulated in degenerative NP cells and that its overexpression accelerated the process of apoptosis. Moreover, USP15 expression levels negatively correlated with AKT phosphorylation in degenerative NP cells. Furthermore, targeting and silencing USP15 with miR‐338‐3p and studying its interaction with FK506‐binding protein 5 (FKBP5) revealed enhancement of FKBP5 ubiquitination, indicating that USP15 is a component of the FKBP5/AKT signalling pathway in degenerative NP cells. Conclusions Our results show that USP15 exacerbates NP degradation by deubiquitinating and stabilizing FKBP5. This in turn results in the suppression of AKT phosphorylation in degenerative NP cells. Therefore, our study provides insights into the understanding of USP15 function as a potential molecule in the network of NP degeneration.

Yiqun Zhang,1 Wei Yu,1 Zhaoyu Ba,2 Shusen Cui,1 Jie Wei,3 Hong Li4 1Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun 130033, China; 2Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; 3Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China; 4College of Physical Science and Technology, Sichuan University, Chengdu 610041, China Background: Due to the increasing number of patients with bone defects, bone nonunion and osteomyelitis, tumor and congenital diseases, bone repair has become an urgent problem to be solved.Methods: In this study, the 3D-printed scaffolds of ternary composites containing mesoporous bioglass fibers of magnesium calcium silicate (mMCS), gliadin (GA) and polycaprolactone (PCL) were fabricated using a 3D Bioprinter.Results: The compressive strength and in vitro degradability of the mMCS/GA/PCL composites (MGPC) scaffolds were improved with the increase of mMCS content. In addition, the attachment and proliferation of MC3T3-E1 cells on the scaffolds were significantly promoted with the increase of mMCS content. Moreover, the cells with normal phenotype attached and spread well on the scaffolds surfaces, indicating good cytocompatibility. The scaffolds were implanted into the femur defects of rabbits, and the results demonstrated that the scaffold containing mMCS stimulated new bone formation and ingrowth into the scaffolds through scaffolds degradation in vivo. Moreover, the expression of type I collagen into scaffolds was enhanced with the increase of mMCS content.Conclusion: The 3D-printed MGPC scaffold with controllable architecture, good biocompatibility, high compressive strength, proper degradability and excellent in vivo osteogenesis has great potential for bone regeneration. Keywords: ternary composites, polymer-based composite, biocompatibility, cytocompatibility, osteogenesis

Accurate and comprehensive data on cervical endplates is essential for developing and improving cervical devices. However, current literature on vertebral disc geometry is scarce or not suitable. The aim of this study was to obtain quantitative parameters of cervical endplates and provide morphometric references for designing cervical devices. In this study, 19 human cervical spine cadaveric specimens were considered. Employing a reverse engineering system, the surface information of each endplate was recorded in digital cloud and then 3D reconstructed. A measurement protocol that included three sagittal and three frontal surface curves was developed. The information of surface curves and endplate concavity were obtained and analyzed. The parametric equations of endplate surfaces were deduced based on coordinates of landmarks, and the reliability was verified. The cervical endplate surface had a trend that to be transversely elongated gradually. The concavity depths of inferior endplates (1.88 to 2.13 mm) were significantly larger than those of superior endplates (0.62 to 0.84 mm). The most-concave points in inferior endplates were concentrated in the central portion, while always located in post-median region in superior endplates. These results will give appropriate guidelines to design cervical prostheses without sacrificing valuable bone stock. The parametric equations applied for generating surface profile of cervical endplates may provide great convenience for subsequent studies.

Background Adjacent segment disease (ASD) is a common complication after lumbar decompression and fusion surgery. Traditional revision-surgery, including posterior lumbar decompression and posterolateral fusion (PLF) or interbody fusion (PLIF) is traumatic. The percutaneous endoscopic transforaminal procedure (PE-TF) has been widely used in patients with lumbar disc disease. However, there are no reports about using PE-TF procedure to treat ASD in the current literature. Objective To compare the clinical outcomes between PE-TF and PLF for single-level ASD after PLF or PLIF. Study design A retrospective study. Setting Department of Spine Surgery. Methods There were 64 patients diagnosed with single-level ASD and accepted revision surgery. 33 patients accepted PE-TF (Group A) and 31 underwent PLF (Group B). Oswestry Disability Index (ODI) and Japanese Orthopedic Association (JOA) scores were used to evaluate clinical outcomes. Complications, length of skin incision, hospitalization time and blood loss were investigated according to patient records. Results All symptoms had improved at the final follow-up. The improvement rate was 82.75% in group A and 86.28% in group B. The satisfactory clinical outcomes were similar in both groups with no recurrence in all cases. PE-TF procedure had significant advantages in the following items: traumatization, cosmetology, hospitalization time and blood loss. Conclusions Clinical outcomes of using PE-TF procedure to treat single-level ASD were similar to those of PLF approach, but PE-TF was less invasive and could shorten hospitalization time.

Detailed and comprehensive geometric data of vertebrae endplates is important and necessary to improve the fidelity of finite element models of the spine, design and ameliorate spinal implants, and understand degenerative changes and biomechanics. In this protocol, a high-speed and highly accurate scanner is employed to convert morphology data of endplate surfaces into a digital point cloud. In the software system, the point cloud is further processed and reconstructed into three dimensions. Then, a measurement protocol is performed, involving a 3D coordinate system defined to make each point a 3D coordinate, three sagittal and three frontal surface curves that are symmetrically fitted on the endplate surface, and 11 equidistant points that are selected in each curve. Measurement and spatial analyses are finally performed to obtain geometric data of the endplates. Parametric equations representing the morphology of curves and surfaces are fitted based on the characteristic points. The suggested protocol, which is modular, provides an accurate and reproducible method to obtain geometric data of vertebral endplates and may assist in more sophisticated morphological studies in the future. It will also contribute to designing personalized spinal implants, planning surgical acts, making clinical diagnoses, and developing accurate finite element models.

Background The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model. Methods Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group. Results The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P P P Conclusions T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.

Zhaoyu Ba,1,* Zhaoxiong Chen,1,* Yufeng Huang,1,* Du Feng,2 Qinghui Zhao,3 Jianguang Zhu,1 Desheng Wu1 1Department of Spinal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; 2Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital, Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China; 3Biobank, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China *These authors contributed equally to this work Introduction: It is predicted that with increased life expectancy in the whole world, there will be a greater demand for synthetic biomedical materials to repair or regenerate lost, injured or diseased tissues. Natural polymers, as biomedical materials, have been widely applied in the field of regenerative medicine. Materials and methods: By incorporation of nanoporous diopside bioglass (nDPB) into gliadin (GL) matrix, macro–nanoporous scaffolds of nDPB/GL composites (DGC) were fabricated by method of solution compressing and particles leaching. Results: The results revealed that the DGC scaffolds possessed well-interconnected macropores of 200–500 µm and nanopores of 4nm, and the porosity and degradability of DGC scaffolds remarkably increased with the increase in nDPB content. In addition, in vitro cell experiments revealed that the adhesion and growth of MC3T3-E1 cells on DGC scaffolds were significantly promoted, which depended on nDPB content. Moreover, the results of histological evaluations confirmed that the osteogenic properties and degradability of DGC scaffolds in vivo significantly improved, which were nDPB content dependent. Furthermore, the results of immunohistochemical analysis demonstrated that, with the increase in nDPB content, the type I collagen expression in DGC scaffolds in vivo obviously enhanced, indicating excellent osteogenesis. Discussion and conclusion: The results demonstrated that the DGC scaffolds containing 30 wt% nDPB (30nDGC) exhibited good biocompatibility and new bone formation ability, which might have a great potential for applications in bone regeneration. Keywords: nanoporous diopside bioglass, gliadin, macro-nanoporous, MC3T3-E1, osteogenesis

Objective To describe a modified technique usied for foraminoplasty in percutaneous endoscopic transforaminal procedure. Methods 58 patients (20 males and 38 females, average age 52.5 years) underwent percutaneous endoscopic transforaminal procedure by using our modified technique. Under the guidance of C-arm fluoroscopy, a kirschner wire was inserted into targeted superior articular process. After expanding the soft tissues, a trepan with the largest diameter was located through the kirschner wire and the angle of trepan was flexible enough to adjust to different operative conditions. This technique could help to avoided using step-by-step larger diameters of trepans without slippage during foraminoplasty. Results With our modified technique, the mean operation time was 65 min (range 50–80 min) and mean estimated blood loss was 12 ml (range 10–30 ml). Fluoroscopy was less (the mean duration of fluoroscopy was 20.4 ± 9.2 s and the mean radiation dose was 0.9 ± 0.2 mSv) and no complications occurred. All foraminoplasties were excellent via CT scans after surgery and all patients were discharged on 2nd day after operation. The results of 58 patients with an average follow-up of 18 (6–36) months demonstrated our eccentric technique to be effective. Conclusion Our eccentric technique could help to avoid step-by-step larger diameters of trepans during foraminoplasty to shorten operation time and reduced the number of fluoroscopy intraoperative.

The expression of the core autophagy kinase, Unc51-like kinase 1 (ULK1), is regulated transcriptionally and translationally by starvation-induced autophagy. However, how ULK1 is regulated during hypoxia is not well understood. Previously, we showed that ULK1 expression is induced by hypoxia stress. Here, we report a new ULK1-modulating microRNA, miR-93; its transcription is negatively correlated with the translation of ULK1 under hypoxic condition. miR-93 targets ULK1 and reduces its protein levels under hypoxia condition. miR-93 also inhibits hypoxia-induced autophagy by preventing LC3-I to LC3-II transition and P62 degradation; these processes are reversed by the overexpression of an endogenous miR-93 inhibitor. Re-expression of ULK1 without miR-93 response elements restores the hypoxia-induced autophagy which is inhibited by miR-93. Finally, we detected the effects of miR-93 on cell viability and apoptosis in noncancer cell lines and cancer cells. We found that miR-93 sustains the viability of MEFs (mouse embryonic fibroblasts) and inhibits its apoptosis under hypoxia. Thus, we conclude that miR-93 is involved in hypoxia-induced autophagy by regulating ULK1. Our results provide a new angle to understand the complicated regulation of the key autophagy kinase ULK1 during different stress conditions.

A retrospective study.To explore the risk factors for reintubation after airway obstruction following anterior cervical surgery.Anterior cervical surgery is an effective surgical therapy for cervical spine disorders. As the anterior approach is adopted more frequently, some rare postoperative complications come under the spotlight, among which, airway obstruction is extremely detrimental. However, the risk factors and the pathogenesis of the airway obstruction still remain unknown. Therefore, finding out the incidence rate and the risk factors of airway obstruction after anterior cervical surgery weighs significantly on preventing airway obstruction.We retrospectively analyzed the history and follow-up data of 774 patients who underwent anterior cervical surgery during January 2007 and June 2016. The patients were divided into two groups according to the occurrence of airway obstruction complication. Patients' age, sex, smoking history, drinking history, the presence of diabetes, body mass index (BMI), course of disease, surgical method, the location of the surgical segment, operation duration and the number of surgical segments were recorded and analyzed. Univariate analysis was conducted for the foregoing factors which might associate with concurrent airway obstruction, to screen out statistically significant factors, followed by a multivariate logistic regression analysis to analyze the relationship between these factors and the incidence rate of reintubation for airway obstruction after anterior cervical surgery.14 of 744 patients developed postoperative airway obstruction followed by reintubation, which makes the incidence rate of 1.81% (14/774) for patients having airway obstruction after anterior cervical surgery. Among the 14 patients, 12 (85.7%) developed airway obstruction within 48 h after surgery, and 2 (14.3%) postoperative showed delayed airway obstruction in 9-11d after surgery. All of them had reintubation. The results of univariate analysis showed that there were statistically significant differences in age, smoking history, body mass index (BMI), surgical method, the location of the surgical segment, operation duration and the number of surgical segments between the two groups (P 0.05). Multivariate logistic regression analysis showed that age (OR = 2.038, 95% CI = 1.045-4.012), smoking (OR = 1.502, 95% CI = 1.012-2.375), BMI (OR = (OR = 1.807, 95% CI = 1.126-2.842), operation duration (OR = 2.503, 95% CI = 1.580-3.966), surgical method (OR = 3.386, 95% CI = 1.036-3.625), the location of the surgical segment (OR = 2.391, 95% CI = 1.085-5.159) and the number of surgical segments (OR = 2.512, 95% CI = 1.564-3.768) were the risk factors for airway obstruction and reintubation after anterior cervical surgery (P 0.05).Age, smoking, obesity, the number of surgical segments, surgical method and surgical segment location are the important factors which may induce airway obstruction after anterior cervical surgery and therefore led to the decision of reintubations.

Study design A retrospective study. Objective To assess the radiographical bony union and clinical outcomes of 207 patients who underwent an anterior cervical discectomy and fusion (ACDF) with only local decompression bone for the treatment of cervical disc degeneration. Summary of background data Many sources of bone graft have been used for ACDF. Autologous iliac bone is most likely suitable for biologic bone fusion ability, but there may be many problems such as high donor site morbidity. Allograft and artificial bones are less effective for bone fusion. Use of local decompression bone could be a good solution. Methods A total of 207 patients (range, 35-80 yr) underwent ACDF, using carbon fiber-reinforced polyetheretherketone cage lled with local decompression bone with anterior cervical plating to treat symptomatic cervical disorders. Computed tomographic scan of the cervical spine was used to assess fusion rates, and Odom's criteria were used to evaluate the clinical outcome. Results Almost all patients had symptomatic improvement, and 97% of patients (201 of 207) exhibited excellent/good clinical outcomes. All interbody disc spacers with local decompression bone achieved successful fusion, confirmed by radiographs and computed tomographic scans, and no cage subsidence occurred at all levels. Conclusion As applied in anterior cervical fusion, the local decompression bone embedded into carbon fiber-reinforced polyetheretherketone cages is enough and can achieve successful fusion, poignant clinical outcomes while achieving no donor site morbidity.

A schwannoma is a benign tumor arising from a schwann cell and occurs mainly in the nerve sheath in the intradural extramedullary region. Schwannomas have been well described as occurring in the lumbar spine, but total cystic degeneration of schwannomas is rarely reported. The authors describe the clinical and radiographic evaluations and treatment of a rare case of an intraextradural totally cystic schwannoma on the lumbar spine. Two patients reported a history of 6 to 12 months of pain accompanied by weakness in the lower extremities. On examination, 1 patient had bilateral lower-extremity muscle strength graded at 4/5, and magnetic resonance imaging revealed a cystic schwannoma (1.5×2.0 cm in the sagittal dimension) at L2–L3. The other patient had a right lower-extremity muscle strength graded at 3/5, and magnetic resonance imaging revealed a cystic schwannoma (2.0×3.0 cm in the sagittal dimension) at L4–L5. The patients underwent operative treatment, and the tumors were completely removed, as were the filum terminale adhered to the tumor. Pedicle screws were used to maintain stability of the lumbar spine. Gross examination of the tumors showed yellowish-white soft contents. Histologic examination confirmed that they were benign totally cystic schwannomas. Postoperatively, the patients’ neurologic symptoms completely resolved. Cystic schwannomas can be diagnosed using preoperative magnetic resonance imaging. The filum terminale cut off the tumor walls did not cause the clinical symptoms in the 2 patients.

Substantial data exist from cadaveric and magnetic resonance imaging studies regarding the position of the conus medullaris in normally developed adults. However, no large studies have documented the position of the conus medullaris in patients with diagnosed lumbar spinal stenosis. To goal of the current study was to determine the position of the conus medullaris within a living adult population with existing pathology of lumbar spinal stenosis. In a retrospective study, 234 patients (110 women and 124 men; mean age, 48.8 years) with diagnosed lumbar spinal stenosis had their T2-weighted, midline, sagittal, spin-echo magnetic resonance imaging studies compared to assess and confirm the position of the conus medullaris. A straight line perpendicular to the long axis of the spinal cord in the median sagittal sequence was subtended to the adjacent vertebra or disk space, and the position was defined in relation to the vertebra or disk space. The conus medullaris position was labeled in relation to the upper, middle, and lower segments of the adjacent vertebral body or the adjacent disk space and assigned numerical values from 1 to 12. The position of the conus medullaris in patients with lumbar spinal stenosis followed a normal distribution. The mean conus medullaris position was mainly within the lower third of the L1 vertebral body (ranged from the middle third of T12 to the upper third of L3). No significant differences existed between men and women with lumbar spinal stenosis. The conus medullaris position was found to be unaffected by the pathology of lumbar spinal stenosis.

Ossification of the posterior longitudinal ligament and ossification of the yellow ligament are the main causes of spinal canal stenosis. This article describes a case of ossification of the posterior longitudinal and yellow ligaments on the lumbar spine. The patient presented with gradually worsening left lower-extremity ache and pain. The deep tendon reflex was hyperreflexia in the lower extremities. Disturbances existed in the blade and bowel. The ossified lesion of ossification of the posterior longitudinal ligament was observed at L5-S1, and plain lateral radiographs and computed tomography revealed ossification of the yellow ligament on L3, which occupied a large part of the spinal canal. Because of the findings on the preoperative radiographs, we performed posterior approach decompression and bone grafting and excisied the ossified lesion. Pedicle screws were inserted from L3 to S1. The patient’s symptoms disappeared postoperatively, and his Japanese Orthopaedic Association score was 25 two weeks postoperatively. No standard surgical procedure exists for the treatment of lumbar ossification of the posterior longitudinal ligament, but it is important to select a surgical procedure according to individual patient conditions. Many factors, such as local mechanic stress, tissue metabolism, high glucose, and genetics, contribute to the progression of ossification of the posterior longitudinal and yellow ligaments on the lumbar spine. However, the mechanism is unclear. Further study and long-term follow-up on lumbar ossification of the posterior longitudinal ligament is needed.