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Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations of type I collagen-related genes, and excessive transforming growth factor-beta (TGF-β) signaling is a common mechanism. TGF-β/Smad signaling has inhibitory effects on osteoblast differentiation and maturation and is mainly transduced and regulated by the internalization of a tetrameric receptor complex comprising types I and II TGF-β receptors (TβRI and TβRII). During internalization, clathrin-mediated endocytosis enhances TGF-β/Smad signaling via Smad2/3 phosphorylation and receptors recycling, while caveolae-mediated endocytosis turns off TGF-β/Smad signaling by promoting receptor ubiquitination and degradation. In this study, using an animal model of OI (Colla2

Background. Metastatic osteosarcoma is a common and fatal bone tumor. Several studies have found that tumor-infiltrating immune cells play pivotal roles in the progression of metastatic osteosarcoma. However, the heterogeneity of infiltrating immune cells across metastatic and primary osteosarcoma remains unclear. Methods. Immune infiltration analysis was carried out via the “ESTIMATE” and “xCell” algorithms in primary and metastatic osteosarcoma. Then, we evaluated the prognostic value of infiltrating immune cells in 85 osteosarcomas through the Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curve. Infiltrations of macrophage M1 and M2 were evaluated in metastatic osteosarcoma, as well as their correlation with immune checkpoints. Macrophage-related prognostic genes were identified through Weighted Gene Coexpression Network Analysis (WGCNA), Lasso analysis, and Random Forest algorithm. Finally, a macrophage-related risk model had been constructed and validated. Results. Macrophages, especially the macrophage M1, sparingly infiltrated in metastatic compared with the primary osteosarcoma and predicted the worse overall survival (OS) and disease-free survival (DFS). Macrophage M1 was positively correlated with immune checkpoints PDCD1, CD274 (PD-L1), PDCD1LG2, CTLA4, and TIGIT. In addition, four macrophage-related prognostic genes (IL10, VAV1, CD14, and CCL2) had been identified, and the macrophage-related risk model had been validated to be reliable for evaluating prognosis in osteosarcoma. Simultaneously, the risk score showed a strong correlation with several immune checkpoints. Conclusion. Macrophages potentially contribute to the regulation of osteosarcoma metastasis. It can be used as a candidate marker for metastatic osteosarcoma’ prognosis and immune checkpoints blockades (ICBs) therapy. We constructed a macrophage-related risk model through machine-learning, which might help us evaluate patients’ prognosis and response to ICBs therapy.

BackgroundDegeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since post-transcriptional regulation may affect gene expression by modulating the translational process of mRNA to protein product, a combined transcriptomic and proteomic study may provide more insight into the key regulatory network of Intervertebral disc degeneration.MethodsIn order to obtain the proteomic and transcriptomic data, we performed label-free proteome analysis on freshly isolated nucleus pulposus cells and obtained transcriptome profiling data from the Gene Expression Omnibus repository. To identify the key regulatory network of intervertebral disc degeneration in nucleus pulposus cells, we performed bioinformatic analyses and established a protein-RNA interacting network. To validate the candidate genes, we performed in vitro experimentation and immunochemistry labeling to identify their potential function during nucleus pulposus degeneration.ResultsThe label-free proteome analysis identified altogether 656 proteins, and 503 of which were differentially expressed between nucleus pulposus cells from degenerated or normal disc cells. Using the existing nucleus pulposus transcriptomic profiling data, we integrated the proteomic and transcriptomic data of nucleus pulposus cells, and established a protein-RNA interacting network to show the combined regulatory network of intervertebral disc degeneration. In the network, we found 9 genes showed significant changes, and 6 of which (CHI3L1, KRT19, COL6A2, DPT, TNFAIP6 and COL11A2) showed concordant changes in both protein and mRNA level. Further functional analysis showed these candidates can significantly affect the degeneration of the nucleus pulposus cell when altering their expression.ConclusionsThis study is the first to use combined analysis of proteomic and transcriptomic profiling data to identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration. Our established protein-RNA interacting network demonstrated novel regulatory mechanisms and key genes that may play vital roles in the pathogenesis of intervertebral disc degeneration.

Background context Laminoplasty is a common surgical method used to treat patients with cervical ossification of the posterior longitudinal ligament (OPLL). Although laminoplasty is preferred over traditional laminectomy, the factors affecting the complications and outcomes are unclear. Recently, sagittal balance indexes have been revealed to be predictors of clinical outcomes in patients with cervical degenerative diseases, but their relationships with laminoplasty-treated OPLL outcomes remains unknown. Purpose The purpose of this study is to evaluate the relationship of preoperative cervical sagittal balance indexes and clinical outcome in laminoplasty treated OPLL patients. Study design This is a retrospective case study. Patient population Between January 2015 and January 2017, 181 consecutively included patients who underwent cervical laminoplasty for OPLL were enrolled (male:female ratio=126:75; mean age=60.2 years). Cervical spine lateral radiographs in neutral, flexion, and extension positions were taken before and 2 years after the surgery. Outcome measures The C2–C7 Cobb angle, T1 slope, C1–C7 sagittal vertical axis (SVA), C2–C7 SVA, CGH (center of gravity of the head)-C7 SVA, cervical JOA (Japanese Orthopedic Association) score, and neck VAS (visual analogue scale) score were measured preoperatively and postoperatively at the 2-year follow-up. Methods The patients were divided into two groups according to changes in the lordotic angle or the recovery rate of the JOA score. The relationships between the postoperative lordosis loss or the clinical outcome and the preoperative variables, including the patient's age, JOA score, C2-C7 Cobb angle, T1 slope, C1-C7 SVA, C2-C7 SVA, and CGH-C7 SVA, were investigated. Results The patients were divided into two groups according to the postoperative change in the C2-C7 Cobb angle. There were no differences in the age, preoperative C2-C7 Cobb angle, C1-C7 SVA, or C2-C7 SVA; there was only a difference in the preoperative CGH-C7 SVA and T1 slope level (p=.038, p=.042). The postoperative JOA and JOA recovery rate were related to the postoperative lordosis loss in cervical alignment (p=.048, p=.031). We again divided the patients into two groups according to the JOA recovery rate and found that only the preoperative CGH-C7 SVA and C1–C7 SVA were related to the neurological outcome (p=.011, p=.047). According to the multivariate logistic regression analysis, higher preoperative CGH-C7 SVA levels were significantly associated with decreases in the lordosis angle postoperatively and the clinical outcome (p=.018, OR=1.225; p=.034, OR=1.654). The ROC (receiver operating characteristic) analysis revealed that the proper cutoff value of preoperative CGH-C7 SVA for predicting the postoperative loss of lordosis and clinical outcomes is 3.8 cm. Conclusion Preoperative cervical sagittal balance indexes are related to the outcomes of OPLL patients after laminoplasty. Patients with high preoperative CGH-C7 SVA levels have a high probability of developing sagittal imbalances and neurological symptoms of the cervical spine, and this measurement can be used as a predictor of outcomes in laminoplasty-treated cervical OPLL patients.

OBJECTIVE: The aim of this study was to evaluate the clinical results of a Bi-needle technique and conventional transforaminal endoscopic spine system (TESSYS) technique for percutaneous endoscopic lumbar discectomy (PELD) in treating patients with intervertebral disc calcification (IDC). BACKGROUND: PELD has gained acceptance for treating patients with IDC. The Bi-needle technique was designed to improve the efficiency and safety of PELD. METHOD: Bi-needle and TESSYS group within each cohort were balanced using 1:1 propensity score matching. Finally, 32 patients with IDC treated by Bi-needle technique from December 2015 to September 2017 were enrolled and 25 patients treated by TESSYS technique from the same spine surgery center between January 2013 and October 2017 were enrolled as controls. RESULTS: Propensity score matching generated 22 Bi-needle and 22 TESSYS patients. There were no significant differences in visual analog scale and lumbar Japanese Orthopaedic Association scores between Bi-needle and TESSYS group. Operative time and rate of complications in the Bi-needle was significantly better than the TESSYS group (p < 0.01). CONCLUSIONS: Both surgical methods achieved good clinical outcomes. However, compared with the TESSSY technique, operative time of the Bi-needle technique is shorter, and rate of complications is lower.

STUDY DESIGN A retrospective study. OBJECTIVE To assess the long-term results of zero-profile spacer for 3-level anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA Although widely used, there are still controversies about the long-term results of zero-profile spacer, especially in multilevel cases. METHODS Cases received 3-level ACDF for cervical spondylotic myelopathy (CSM) using either zero-profile spacer (n = 27) (ZP Group), or plate and cages (n = 34) (PC Group), and with 5-year follow-up were reviewed. Neurological function and life quality were assessed by modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and Short-Form 36 (SF-36) score. Disc height, cervical lordosis, fusion rate, and surgical complications were observed. RESULTS Neurological recovery and life quality improvement were similar in both groups. Disc height and cervical lordosis (C2-7 Cobb angle) were well restored after operations, but lost in both groups during follow-up. Loss of correction (LOC) in disc height was larger in ZP Group (11.38% vs 5.71%, P

Indications and clinical outcomes of percutaneous endoscopic thoracic discectomy(PETD) in treating thoracic disc herniation is rarely reported and still controversial. We reported an unsatisfied recovery of thoracic disc herniation with PETD, treated by a second posterior thoracic laminectomy and Ponte osteotomy.A male presented with lower extremity weakness and stagger caused by T3/4 intervertebral disc herniation. The upper thoracic curve was in excessive kyphosis with T2-5 Cobb angle of 34.3 degrees. The preoperative ODI score was 34 and Roelzs's JOA score was 14. Percutaneous transforaminal endoscopic thoracic discectomy (PETD) from a posterior lateral approach was performed. At five-month follow-up, his thoracic back pain and staggering gait did not improve. The postoperative T2-5 Cobb angle was 32.1 degrees, the ODI score was 24 and Roelzs's JOA score was 14. A second posterior thoracic decompression this time with fixation was performed, but no disc herniation was detected. A Ponte osteotomy was performed to correct the kyphosis. One month after the second surgery, muscle strength of the lower limbs was improving with the T2-5 Cobb angle decreased to 19.4 degrees, the ODI score decreased to 10 and Roelzs's JOA score increase to 16. Six month later, the ODI score decreased to 0 and Roelzs's JOA score improved to 18. In review of the literature, PETD doesn't guarantee the patient a satisfactory neurological recovery for kyphotic thoracic disc herniation. Posterior decompression with Ponte osteotomy may be beneficial to release the tension and decompression of the spinal cord tension.Thoracic disc herniation with kyphosis angle20 degrees (T2-5), percutaneous endoscopic thoracic discectomy is not likely to get good neurologic results. Posterior laminectomy with ponte osteotomy might be beneficial for these patients to induce dorsal drifting of the spinal cord from anterior herniation.

To evaluate the clinical and radiographic outcomes of an anterior-only approach for the correction of severe cervical kyphotic deformities.We performed a retrospective study of 33 consecutive patients with severe cervical kyphosis treated with an anterior cervical operation and preoperative and intraoperative skull traction. Cobb angle, kyphosis index (KI), kyphosis level, C2-7 sagittal vertical axis (SVA), and T1 slope were measured. The preoperative and postoperative Japanese Orthopedic Association (JOA) scores, visual analog scale (VAS) score for neck pain, Neck Disability Index (NDI) scores, and cervical alignment were compared.The mean angle of the kyphosis was 83.2 ± 20.4°. The mean Cobb angle of the operative region was 71.7 ± 18.5° preoperation, which was reduced to 10.6 ± 5.7° postoperation (mean correction, 85.2%). The mean KI was 75.1 ± 18.2 preoperation, which was reduced to 14.4 ± 9.1 postoperation (mean correction, 80.8%). The preoperative and postoperative mean C2-7 Cobb angle was 53.8 ± 16.5° and 14.7 ± 7.6°, respectively. The preoperative and postoperative mean C2-7 SVA was 3.9 ± 14.5 mm and 12.8 ± 7.3 mm, respectively. The preoperative and postoperative mean T1 slope was -9.4 ± 15.7° and 7.3 ± 13.1°, respectively. The average postoperative C2-7 Cobb angle, Cobb angle of the operative region, KI, C2-7 SVA, and T1 slope changed significantly compared with preoperative values (P0.05). The average postoperative JOA, VAS, and NDI scores improved significantly compared with preoperative scores (P0.05).Preoperative and intraoperative skull traction combined with anterior-only cervical operation may be a safe and effective technique for treating severe cervical kyphosis. If the postoperative correction is80%, sufficient decompression could be achieved.

The purpose of this study was to determine the number of cases needed to achieve the level of competence for percutaneous endoscopic lumbar diskectomy (PELD) via the bi-needle technique using the cumulative summation test for learning curve (LC-CUSUM).A retrospective design was used. We included 60 patients who underwent a single-level PELD via the bi-needle technique performed by a single surgeon. The surgeon had 5 years of experience in open surgery including the transforaminal endoscopic spine system and Yeung endoscopic spine system but no experience in the bi-needle technique. Surgery success was defined as an operative time60 minutes, and the acceptable procedure was completed within 3 times of C-arm fluoroscopies. The LC-CUSUM was used to analyze the data.The average operative time for PELD via the bi-needle technique was 58.3 ± 12.4 minutes. The mean operative time was 65.7 ± 12.1 minutes in the early learning period (30 cases) and 51.0 ± 7.5 minutes in the late learning period (30 cases) (P0.05). On the basis of the evaluation indexes of the operative time and radioactive exposure, the LC-CUSUM signaled proficiency for the bi-needle technique at the 50th-54th operation. Seven cases of complications were observed during the whole learning process, with 6 in the early period and 1 in the late period (P0.05).The novel bi-needle technique is safe and effective for PELD with appropriate patients, and the learning curve is acceptable. A substantial learning period (50-54 cases) is needed before a spine surgeon can master the bi-needle technique.

BACKGROUND CONTEXT The presence of ossification of posterior longitudinal ligament (OPLL) can lead to symptomatic spinal cord compression and myelopathy. The surgical approach in patients with myelopathy is influenced by the presence of OPLL. Diagnose of OPLL currently requires computed tomography which incurs a large dose of radiation. Circulating disease-specific microRNAs (miRNAs) may serve as promising diagnostic markers with no radiation and easy accessibility for OPLL patients. PURPOSE The purpose of this study is to evaluate the accuracy and significance of OPLL-specific microRNAs in discriminating OPLL from normal and intervertebral disc degenerated (IDD) patients by detecting the microRNAs’ plasma level. STUDY DESIGN/PATIENT SAMPLES The level of microRNAs in OPLL patients’ plasma or serum were detected and compared to that of normal and IDD patients to evaluate the accuracy and significance of diagnosing OPLL. METHODS Taking advantage of the high through-put microRNA sequencing data, we selectively tested the ten most differentially regulated microRNAs in patients with: (1) radiologically diagnosed OPLL (n = 68), (2) radiologically diagnosed disc herniated patients with no evidence of OPLL (n = 45), (3) non-OPLL and nonmyelopathy patients (n = 53).The feasibility of the biomarkers in identifying OPLL was assessed through analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve (AUC) values. RESULTS Of the ten miRNAs validated, miR-10a-3p, miR-10a-5p, miR-563, miR-210-3p, and miR-218-3p showed significance between OPLL and non-OPLL blood samples. While miR-10a-5p, miR-563, and miR-210-3p showed high accuracy and significance in identifying OPLL from other groups individually, and an index that combines these miRNAs achieved the highest accuracy and AUC among these individual miRNAs. CONCLUSIONS Analysis of miR-10a-5p, miR-563, and miR-210-3p may be of important value in diagnosing OPLL. These markers maybe useful in a clinical setting in the early detection of OPLL patients by blood testing.

Lumbar disc herniation (LDH) is a common cause for low back pain. In this study, we aimed to explore the effects of a specific Lactobacillus paracasei (L. paracasei), L. paracasei S16, on the symptoms of LDH using a mouse model of LDH. The results showed that L. paracasei S16 treatment improved the behavior, increased the cell proliferation, and decreased the apoptosis in LDH mice. Moreover, L. paracasei S16 treatment alleviated the aberrant inflammation response in the LDH mice, which is characterized by the decreased anti-inflammatory cytokines, increased pro-inflammatory cytokines, and decreased percentage of Th1 and Th2 cells and Th17/Treg ratio. 16S rRNA sequencing results showed that the LDH mice treated with L. paracasei S16 have higher relative abundance of Lachnospiraceae and Ruminococcaceae and lower abundance of Lactobacillaceae than mice in the LDH group. Additionally, the serum metabolites involved in the linoleic acid metabolism, alanine. aspartate, and glutamate, glycerophospholipid, and TCA cycle were significantly decreased and the metabolite involved in purine metabolism was significantly increased after the L. paracasei S16 treatment in the LDH mice. These results showed that administration of L. paracasei S16 can improve inflammation response, alter gut microbiota, and modulate serum metabolomics in a mouse model of LDH.

Study Design A retrospective observational study. Objective To describe a novel outcome indication system, the posterior compression score (PCS), and investigate its clinical value in cervical ossification of the posterior longitudinal ligament (OPLL) patients treated with laminoplasty. Methods A total of 282 OPLL patients who underwent laminoplasty from January 2013 to December 2018 were reviewed. The patients were divided into high-score (HS) or low-score (LS) groups based on whether the PCS was over 8. Propensity score matching analysis with a caliper of .1 was used to attenuate the potential selection bias. Clinical measurements, including the Japanese Orthopedic Association (JOA) score, visual analog scale (VAS), neck disability index (NDI), and radiological measurements, including C2–C7 lordotic angle and range of motion (ROM), were compared between the groups. Results The mean follow-up period was 29.87 ± 9.17 months. There were no significant differences between the two groups regarding patients’ baseline demographical and clinical characteristics after propensity score matching. No significant differences were found in the operative time, blood loss, postoperative VAS score for neck and arm pain, postoperative C2–C7 lordotic angle, or postoperative ROM ( P > .05). However, the postoperative JOA score and recovery rate were significantly higher in the HS group than in the LS group, while the postoperative NDI was significantly lower in the HS group ( P < .05). Conclusion OPLL patients with higher PCS scores displayed better clinical outcomes. The novel PCS system is suggested to be a reliable scoring system for surgical outcome evaluation in patients with cervical OPLL.

The destruction of low oxygen microenvironment played critical roles in the pathogenesis of intervertebral disk degeneration (IVDD). In this study, high oxygen tension (HOT) treatment upregulated integrin α6(ITG α6) expression, which could be alleviated by blocking PI3K/AKT signaling pathway. And the levels of ITG α6 expression were increased in the NP tissue from IVDD patients and IVDD rat model with mild degeneration, which were reduced as degeneration degree increases. Further studies found that ITG α6 could protect NP cells against HOT-induced apoptosis and oxidative stress, and protect NP cells from HOT-inhibited ECM proteins synthesis. ITG α6 upregulation by HOT contributed to maintain a NP tissue homeostasis through the interaction with hypoxia inducible factor-1α (HIF-1α). Furthermore, silencing of ITG α6 in vivo could obviously accelerate puncture-induced IVDD. Taken together, ITG α6 upregulation by HOT in NP cells might be a protective factor in IVDD as well as restore NP cell function.

Alendronate (Aln) has been the first-line drug for osteogenesis imperfecta (OI), while the comparable efficacy of Aln and strontium ranelate (SrR) remains unclear. This study is aimed at comparing the effects of SrR and Aln treatment in a mouse model of OI. Three-week-old oim/oim and wt/wt female mice were treated with SrR (1800 mg/kg/day), Aln (0.21 mg/kg/week), or vehicle (Veh) for 11 weeks. After the treatment, the average number of fractures sustained per mouse was significantly reduced in both SrR- and Aln-treated oim/oim mice. The effect was comparable between these two agents. Both SrR and Aln significantly increased trabecular bone mineral density, bone histomorphometric parameters (bone volume, trabecular number, and cortical thickness and area), and biomechanical parameters (maximum load and stiffness) as compared with the Veh group. Both treatments reduced bone resorption parameters, with Aln demonstrating a stronger inhibitory effect than SrR. In contrast to its inhibitory effect on bone resorption, SrR maintained bone formation. Aln, however, also suppressed bone formation coupled with an inhibitory effect on bone resorption. The results of this study indicate that SrR has comparable effects with Aln on reducing fractures and improving bone mass and strength. In clinical practice, SrR may be considered an option for patients with OI when other medications are not suitable or have evident contraindications.

To investigate whether different quantitative measurements of increased signal intensity (ISI) on T2-weighted magnetic resonance imaging are useful for predicting surgical outcome in patients with cervical spondylotic myelopathy (CSM).We retrospectively reviewed 108 patients with ISI who underwent surgery for CSM. Clinical outcome was evaluated via the Japanese Orthopaedic Association (JOA) score and the recovery rate. Patients were divided into 2 groups based on the JOA recovery rate: good (≥50%) and fair (50%). The quantitative measurements of ISI included the maximum vertical length and the signal change ratio (SCR). C2-C7 sagittal alignment, C2-C7 sagittal vertical axis, C2-C7 range of motion, maximum spinal cord compression, and maximum canal compromise also were assessed.There were no significant differences in cervical sagittal alignment parameters between the groups. Multivariate analysis showed that a longer duration of symptoms, a lower preoperative JOA score, a longer preoperative ISI length, and a greater preoperative SCR were negatively associated with clinical outcomes. Receiver operating characteristic curve analysis showed that the best cutoff values of ISI length and SCR as negative predictors of surgical outcome were 15.50 mm and 1.56, respectively, and the areas under the receiver operating characteristic curve of preoperative ISI length, SCR that discriminate recovery rate of JOA score (≥50%,50%) were 0.8507, 0.8422, respectively, and was 0.8903 for a combination of the 2.Duration of symptoms, preoperative JOA score, preoperative ISI length, and SCR can reflect surgical outcome in patients with CSM; however, cervical sagittal alignment may not affect surgical outcome. Combining ISI length and SCR to depict ISI on T2-weighted magnetic resonance imaging is optimal and accurate. Patients with ISI length15.50 mm and SCR1.56 have fair surgical recovery.

Background/Aims: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1β, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1β. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1β mediated NP cell degeneration and apoptosis. Methods: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1β (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1β for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. Results: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1β induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1β induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1β. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1β, this function was blocked by autophagy inhibitor, 3-methyladenine. Conclusion: APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.

Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the development of OPLL. Here, we set out to unveiling the detailed mechanism of those altered OPLL-specific microRNAs. We screened a set of differentially expressed OPLL-specific microRNAs from the previous sequencing data and showed that microRNA-10a actively modulates the ossification of posterior ligament cells in vitro. Using a tissue-engineered scaffold grown from 4-week-old BALB/c homozygous nude mice, we found that altered microRNA-10a expression in posterior ligament cells indeed affected the heterotopic bone formation in vivo. Furthermore, computational analysis showed that the negative ossification regulator ID3 is a functional target gene of microRNA-10a, and its expression was also significantly altered during microRNA-10a modulation both in vitro and in vivo. Also, we have demonstrated that the ossification promoting function of microRNA-10a requires ID3, as ID3 actively inhibits RUNX2. Thus, we identified a critical role for highly altered OPLL-specific microRNA-10a in regulating the development of OPLL by modulating the ID3/RUNX2 axis.

The aim of this study was to investigate the effect of lumbar spine selective nerve root block (SNRB) experience on the learning efficiency of percutaneous endoscopic lumbar discectomy (PELD) for junior trainees. A total of 480 patients undergoing single-level PELD performed by eight junior trainees were included. The trainees were divided into two groups based on whether they had previous SNRB experience (group A, yes; group B, no). Surgical proficiency was defined as total operation time less than 65 minutes and cumulative radiation exposure time no more than 40 seconds. The learning curve was analyzed by cumulative summation (CUSUM) test. Clinical evaluations included Macnab classification, visual analog scale (VAS)-low back score, VAS-leg score, and Oswestry Disability Index (ODI). Follow-up information at 12 months was also obtained. Integral number of cases before achieving an acceptable surgical level in group A (47.75 ± 2.50 cases) was significantly smaller than that in group B (56.50 ± 1.29 cases, p

Background: We know of five cases of cervical nerve root variants that have been reported, all of which were found during posterior cervical surgery. We reported two cases of cervical nerve root va...

Objective The objective of our study was to verify the hypothesis that the expression of connective tissue growth factor (CTGF/CCN2), a key molecule essential for the maintenance of nucleus pulposus (NP) matrix homeostasis, is regulated by osmolarity and intracellular calcium in NP cells. Methods Gene and protein expression levels of CCN2 were assessed using quantitative real-time PCR and western blot. Transfections and dual luciferase assays were performed to measure the effect of hyperosmolarity, tonicity enhancer binding protein (TonEBP) and Ca2+-calcineurin (Cn)-NFAT signaling on CCN2 promoter activity. Results Cultured in hyperosmotic media, there was a significant decrease in the levels of CCN2 promoter activity, gene and protein expression in NP cells. The JASPAR database was used to analyze the construction of human CCN2 promoter, we found conserved TonE and NFAT binding sites. We then investigated whether TonEBP controlled CCN2 expression. Forced expression of TonEBP in NP cells showed that TonEBP negatively regulated CCN2 promoter activity, while suppression of TonEBP induced CCN2 promoter activity and expression. We then examined if Ca2+-Cn-NFAT signaling participated in the regulation of CCN2 expression. Co-expression of CCN2 reporter with individual NFAT1–4 expression plasmids and/or calcineurin A/B constructs suggested this signaling pathway played a role in the regulation of CCN2expression in NP cells. Conclusions Results of these studies illustrated that the expression of CCN2 in NP cells was regulated by the NFAT family through a signaling pathway network involving both activator (Ca2+-Cn-NFAT signaling) and suppressor (Hyperosmolarity-TonEBP) molecules.

We investigated a series of long-term soil samples (1976–2015) collected from a paddy field that underwent a conversion of cropping systems from double cropping to single cropping in 1991, with consistently different fertilization treatments. The fertilization treatments include (i) chemical fertilizer, (ii) chemical fertilizer + rice straw, (iii) chemical fertilizer + cattle manure compost, and (iv) chemical fertilizer + rice straw + fused phosphate + calcium silicate. We extracted dissolved organic matter (DOM) from the soil samples and analyzed it for the concentration of humic substances as well as for optical properties using ultraviolet-visible and excitation-emission matrix (EEM) spectroscopy. Different fertilization treatments did not significantly (P > 0.05) affect DOM and humic substance concentrations, while the soil total carbon (TC) content and DOM concentration consistently increased in the double cropping system and decreased in the single cropping system. The DOM/TC ratio, which is an indicator of the proportion of the labile fraction in TC pool, also showed a similar pattern. These results indicate that cropping systems had a larger effect on DOM concentration than the fertilization treatments. Five fluorescent components identified by parallel factor analysis of EEMs (three humic-like and two protein-like components) showed significant differences in the relative abundances under the different fertilization treatments. The manure compost application resulted in a higher tyrosine-like component relative abundance than the other chemical fertilizer applications. Overall, fertilization affected the DOM composition, while the cropping systems impacted both the concentration and spectroscopic property of paddy soil DOM.

To compare the clinical and radiologic outcomes of 3 anterior surgical techniques for the treatment of 3-level cervical spondylotic myelopathy (CSM) and the evolution of intramedullary T2-weighted increased signal intensity (ISI).A total of 98 consecutive patients (61 males, 37 females) with 3-level CSM who underwent anterior cervical surgery between January 2006 and January 2016 were retrospectively enrolled. Based on different anterior reconstructive techniques, the patients were divided into 3 groups: anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), and hybrid decompression and fusion (HDF) groups. The Japanese Orthopaedic Association score and its recovery rate were used to evaluate the clinical outcomes. The cervical alignment and range of motion were used to assess radiologic outcomes. In addition, the signal change ratio and length of ISI were used to measure the ISI.No statistical differences in preoperative factors were found among the 3 groups (P0.05). Although the HDF group had intermediate surgery time and blood loss compared with other groups (P0.05), it achieved greater postoperative Japanese Orthopaedic Association score and recovery rate than other groups (P0.05). The postoperative C2-C7 lordotic angle and postoperative range of motion in the HDF group were similar to that in the ACDF group (P0.05), both greater than that in the ACCF group (P0.05). The incidence of complications in the HDF group was close to the ACDF group (P0.05), and both groups were lower than that in the ACCF group (P0.05). In addition, the postoperative signal change ratio in the HDF group was lower than in other groups (P0.05). The postoperative length of ISI in the HDF group was similar to the ACCF group (P0.05), which was both shorter than that in the ACDF group (P0.05).For patients with 3-level CSM with ISI on T2-weighted MRI, HDF can be considered as the optimal technique that achieves better clinical and radiologic outcomes than the ACDF or ACCF procedure. HDF also has a better postoperative regression of ISI compared with the ACDF or ACCF procedure, which may potentially be an important indicator for improving surgical outcomes.

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three-week-old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR-treated oim/oim mice was significantly reduced compared to Veh-treated oim/oim mice. Micro-computed tomographic (μCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild-type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. © 2015 American Society for Bone and Mineral Research.

Background The City of Hope Quality of Life-Ostomy Questionnaire is a widely accepted scale to assess quality of life in ostomy patients. However, the validity and reliability of the Chinese version (C-COH) have not been studied. Objective The objective of the study was to assess the validity and reliability of the C-COH among ostomy patients sampled from Shanghai from August 2010 to June 2011. Methods Content validity was examined based on the reviews of a panel of 10 experts; test-retest was conducted to assess the item reliabilities of the scale; a pilot sample (n = 274) was selected to explore the factorial structure of the C-COH using exploratory factor analysis; a validation sample (n = 370) was selected to confirm the findings from the exploratory study using confirmatory factor analysis (CFA). Statistical package SPSS version 16.0 was used for the exploratory factor analysis, and Amos 17.0 was used for the CFA. Results The C-COH was developed by modifying 1 item and excluding 11 items from the original scale. Four factors/subscales (physical well-being, psychological well-being, social well-being, and spiritual well-being) were identified and confirmed in the C-COH The scale reliabilities estimated from the CFA results for the 4 subscales were 0.860, 0.885, 0.864, and 0.686, respectively. Conclusions Findings support the reliability and validity of the C-COH. Implications for practice The C-COH could be a useful measure of the level of quality of life among Chinese patients with a stoma and may provide important intervention implications for healthcare providers to help improve the life quality of patients with a stoma.

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by brittle bones with increased fracture risk. Although current treatment options to improve bone strength in OI focus on antiresorptive bisphosphonates, controlled clinical trials suggest they have an equivocal effect on reducing fracture risk. Strontium ranelate (SrR) is a promising therapy with a dual mode of action that is capable of simultaneously maintaining bone formation and reducing bone resorption, and may be beneficial for the treatment of OI. In this study, SrR therapy was investigated to assess its effects on fracture frequency and bone mass and strength in an animal model of OI, the oim/oim mouse. Three-week-old oim/oim and wt/wt mice were treated with either SrR or vehicle (Veh) for 11 weeks. After treatment, the average number of fractures sustained by SrR-treated oim/oim mice was significantly reduced compared to Veh-treated oim/oim mice. Micro-computed tomographic (μCT) analyses of femurs showed that both trabecular and cortical bone mass were significantly improved with SrR treatment in both genotypes. SrR significantly inhibited bone resorption, whereas bone formation indices were maintained. Biomechanical testing revealed improved bone structural properties in both oim/oim and wild-type (wt/wt) mice under the treatment, whereas no significant effects on bone brittleness and material quality were observed. In conclusion, SrR was able to effectively reduce fractures in oim/oim mice by improving bone mass and strength and thus represents a potential therapy for the treatment of pediatric OI. © 2015 American Society for Bone and Mineral Research.

Objective To investigate the clinical and imaging predictors of surgical outcomes in patients with ossification of the posterior longitudinal ligament (OPLL). Materials and Methods From May 2010 to April 2012, a total of 200 consecutive patients with cervical OPLL were recruited for this study. Of them, 184 patients (130 men and 54 women) who could be tracked for more than 24 months after surgery were finally included for analysis. Their demographic, clinical and radiological data were collected preoperatively. The recovery ratio in terms of JOA score was used to assess the outcome of the patients preoperatively and at 2 years postoperatively. A JOA recovery rate less than 50% was considered a poor outcome. Results Compared with good outcome group, an older mean age at operation, a longer mean duration of symptoms, a lower mean pre-operativer JOA score, and a higher proportion of diabetics were observed in poor outcome group. Patients in poor outcome group were more likely to present kyphotic cervical alignment, smaller mean transverse area of the spinal cord, and intramedullary signal abnormalities. The result of multivariate stepwise logistic regression showed that a longer duration of symptoms and the presence of T1 hypo-intensity intramedullary changes on MRI were significant risk factors of lower JOA recovery ratios. Conclusion A longer duration of symptom, T1 hypointensity on MRI and a history of minor trauma were highly predictive of a poor outcome for patients undergoing surgical treatment of OPLL. Age at operation, the history of diabetes, the preoperative JOA score, the transverse area of the spinal cord and T2 hyper-intensity on MRI were also associated with the prognosis of OPLL.

To evaluate the role and value of Changhai fulcrum bending radiograph(CH-FBR) in curve flexibility assessment of adolescent idiopathic scoliosis(AIS) patients.Thirty-seven AIS patients treated between June 2012 and August 2013 were enrolled, including 31 female and 6 male patients whose age ranged from 10 to 19 years, averaged of 15.0 years. The assessment of radiographs included preoperative standing posterior-anterior radiograph, supine side-bending radiograph, traditional fulcrum bending radiograph, Changhai fulcrum bending radiograph and postoperative standing posterior-anterior radiograph. Postoperatively, radiographs were assessed at one week. The CH-FBR was performed at the lowest height and the optimized height which means the weight on the fulcrum touch the maximum. All measurements of angle were made with use of the Cobb method. The flexibility of the curve as well as the correction rate and fulcrum bending correction index (FBCI) were calculated for all patients. The maximum height of CH-FBR, basic weight and maximum weight were measured for all AIS. Paired t-tests were used to assess differences between preoperative and postoperative curves within group samples. The Pearson correlation coefficients were calculated using bivariate analysis between CH-FBR flexibility rate and correction rate, the maximum height of CH-FBR and maximum weight, the height changes of CH-FBR and weight changes.A total of 46 curves were involved in this study, including 28 thoracic and 18 thoracolumbar/lumbar curves. Preoperatively, the mean Cobb angle of the 46 structural curves was 47° ± 11°. Postoperatively, the mean Cobb angle was 11° ± 5°. Cobb's angle in supine side-bending(t = 7.2, P = 0.001), traditional fulcrum bending (t = 7.1, P = 0.001) and lowest height of Changhai fulcrum bending (t = 6.5, P = 0.001) were significantly different from the postoperative Cobb angle; Cobb's angle in traditional FBR (t = 11.0, P = 0.001) and lowest height of Changhai fulcrum bending (t = 13.6, P = 0.001) were significantly different from the optimized height CH-FBR Cobb angle. There was no significant difference found between traditional FBR Cobb angle and lowest height CH-FBR Cobb angle (t = 2.0, P = 0.051), optimized height CH-FBR Cobb angle and postoperative Cobb angle (t = 0.9, P = 0.36), lowest height CH-FBR Cobb angle and traditional FBR Cobb angle(t = 2.0, P = 0.051). The maximum height of CH-FBR, basic weight and maximum weight were (29.6 ± 1.4)cm,(20 ± 6)kg, and (40 ± 6) kg. Preoperatively, the mean Cobb angle of the 28 structural curves(main thoracic curves) was 46° ± 11°. Postoperatively, the mean Cobb angle was 12° ± 6°. Preoperatively, the mean Cobb angle of the 18 structural curves(thoracolumbar/lumbar curves) was 49° ± 12°. Postoperatively, the mean Cobb angle was 10° ± 5°. The results were same in 28 structural curves, 18 structural curves as well as 46 curves. Correlation analysis of 46 curves indicated that the maximum height of CH-FBR positively correlated with maximum weight (r = 0.69, r(2) = 0.47, P = 0.001), the height changes of CH-FBR positively correlated with weight changes on CH-FBR (r = 0.62, r(2) = 0.38, P = 0.001).CH-FBR is a more reliable and effective method than traditional FBR and supine side-bending for curve flexibility evaluation in AIS patients. Moreover, compared to the traditional FBR and side-bending radiograph, the flexibility suggested by the optimized height CH-FBR more closely approximates the postoperative result made by pedicle screws fixation and fusion.

We appreciate the kind words offered by Dr. Raggio and his colleagues about our recent article[1]. Dr. Raggio highlighted what they considered to be three problems with our discussion and reference. We address these three problems below. This article is protected by copyright. All rights reserved