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Mingyi Yang,1,* Haishi Zheng,1,* Yani Su,2,* Ke Xu,1 Qiling Yuan,1 Yirixiati Aihaiti,1 Yongsong Cai,1 Peng Xu1 1Department of Joint Surgery, HongHui Hospital, Xi’an Jiaotong University, Xi’an, Shanxi, 710054, People’s Republic of China; 2Yan’an University Affiliated Hospital, Yan’an, Shanxi, 716000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Xu, HongHui Hospital, Xi’an Jiaotong University, No. 555, Youyi East Road, Beilin District, Xi’an City, Shaanxi Province, 710054, People’s Republic of China, Tel +86 13772090019, Email sousou369@163.comObjective: Rheumatoid arthritis (RA) is a nonspecific, chronic, systemic autoimmune disease characterized by symmetric polyarticular synovitis. Bioinformatics analysis of potential biomarkers, mRNA–miRNA–lncRNA axes, and signaling pathways in the pathogenesis of RA provides potential targets and theoretical basis for further research on RA.Methods: The GSE1919 and GSE77298 datasets were downloaded from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo). Perl was used to perform data merging, and R was used to perform batch correction. The “limma” package of R was used to screen differentially expressed genes, and the “clusterProfiler” package was used to perform enrichment analysis of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Search Tool for the Retrieval of Interacting Genes/Proteins was used to construct the protein–protein interaction network, Cytoscape was used for module analysis, and R was used to screen for hub genes. GraphPad Prism was used to plot the receiver operating characteristic curve of the hub genes. Gene set enrichment analysis and competitive endogenous RNA network analysis were performed on hub genes with the greatest diagnostic values. The hub gene with the greatest diagnostic value was verified using immunohistochemical staining.Results: We obtained nine hub genes (ITGB2, VAMP8, HLA-A, PTAFR, SYK, FCER1G, HLA-DPB1, LCP2, and ACTR2) and four mRNA–miRNA–lncRNA axes (ITGB2-hsa-miR-486-3p-SNHG3, ITGB2-hsa-miR-338-5p-XIST, ITGB2-hsa-miR-5581-3p-XIST, and ITGB2-hsa-miR-1226-5p-XIST) related to the pathogenesis of RA. The nine hub genes were highly expressed, and ITGB2 had the highest diagnostic value for RA. We also identified signaling pathways related to the pathogenesis of RA: Fc epsilon Rl and chemokine signaling pathways. The immunohistochemical results showed that ITGB2 expression was significantly upregulated in RA.Conclusion: The hub genes, mRNA–miRNA–lncRNA axes, and signaling pathways related to RA pathogenesis identified in this study provide a new research direction for the mechanism, diagnosis, and treatment of RA.Keywords: rheumatoid arthritis, synovial, genes, lncRNA

Background Laminectomy is a traditional method for treating lumbar diseases; however, the destruction of the posterior structures may cause postoperative symptoms. An individualized poly-ether-ether-ketone (PEEK) artificial lamina was designed to reconstruct the posterior structures after laminectomy. This study aimed to explore the biomechanical effects of reconstruction of the posterior structures with an individualized PEEK artificial lamina using validated finite element models. Objective To examine the biomechanical effects of individualized PEEK artificial lamina on postlaminectomy lumbar. Methods A finite element (FE) model of L3-5 was developed based on computed tomography images. Four surgical models (laminectomy, artificial lamina alone, ligament reconstruction, and osseointegration) were constructed, representing different stages of L4 artificial lamina implantation. The range of motion (ROM), intradiscal pressure (IDP), stresses in the annulus fibrosus at the surgical level and cephalad adjacent level, and stresses in the artificial lamina and screws were measured. Results The ROM, IDP, and stresses in the annulus fibrosus of the different artificial lamina models decreased compared to those of the laminectomy model at both surgical and adjacent levels for all motion patterns, most notably in the osseointegration model. In addition, the results of the stresses in the implants showed that the artificial lamina could enhance the lumbar isthmus and disperse the abnormally concentrated stresses after laminectomy. Conclusion The application of a PEEK artificial lamina has the potential to stabilize the postlaminectomy lumbar spine and prevent adjacent segment disease (ASD) and iatrogenic lumbar deformities, resulting in a reduction in the incidence of post-lumbar surgery syndrome.

Exosomes derived from mesenchymal stromal cells (MSCs) have emerged as novel drug and gene delivery tools. Current study aimed to elucidate the potential therapeutic role of human placental MSC (hPLMSC)-derived exosomes carrying AntagomiR-4450 (EXO-AntagomiR-4450) in intervertebral disc degeneration (IDD) progression. Initially, the differentially expressed miRNAs related to IDD were identified by microarray analysis, which provided data predicting the interaction between microRNA-4450 (miR-4450) and zinc finger protein-121 (ZNF121) in IDD. Next, miR-4450 and ZNF121 were elevated or silenced to determine their effects on the damage of nucleus pulposus cells (NPCs) treated with tumor necrosis factor α (TNF-α). The therapeutic effects of EXO-AntagomiR-4450 on NPCs were verified both in vitro and in vivo (15-week-old C57BL/6 male mice); especially gait analysis and fluorescent molecular tomography were used in live mice with IDD. Our results revealed that miR-4450 was highly expressed, while ZNF121 was poorly expressed in IDD patients and NPCs treated with TNF-α. Furthermore, miR-4450 was identified to specifically target ZNF121. In addition, the inhibition of miR-4450 exerted an alleviatory effect on the inflammation, apoptosis, and damage of the NPCs by upregulating ZNF121 (all

Purpose This article aimed to investigate the mechanism by which MALAT1 and miR-129 affected the development of osteosarcoma. Methods Tumor tissues and adjacent tissues of 23 osteosarcoma patients were collected. Normal osteoblasts hFOB1.19 and osteosarcoma cells MG63 were cultured. MG63 cells were transfected and grouped: si-negative control (NC) group, si-MALAT1 group, miR-129 NC group, miR-129 mimics group, p-Empty vector group, p-MALAT1 group, p-MALAT1+ miR-129 mimics group, and p-MALAT1+ si-TGIF2 group. Luciferase reporter assay, Cell Counting Kit-8 assay, Transwell assay, quantitative reverse transcription PCR, Western blot, and Pearson correlation analysis were performed. Results MALAT1 expression in tumor tissues and MG63 cells was increased (P

Cartilage‑derived morphogenetic protein‑1 (CDMP1) is a polypeptide growth factor with specific cartilage inducibility, which is predominantly expressed in the developmental long bone cartilage core and in the pre‑cartilage matrix in the embryonic stage. The aim of the present study was to investigate the roles and the mechanisms of CDMP1 overexpression on the apoptosis of rat dorsal root ganglia (DRG) neurons that were induced by inflammatory cytokines. Cell counting Kit‑8 assay, flow cytometry and TdT‑mediated dUTP nick‑end labeling assay were performed to examine cell viability and apoptosis. ELISA, hematoxylin and eosin staining and immunohistochemistry assays were performed to examine the levels of several factors in DRG tissues. Western blot analysis and reverse transcription‑quantitative polymerase chain reaction assays were used to determine the mRNA and protein expression levels, respectively. The results demonstrated that CDMP1 expression was downregulated, while inflammatory cytokine expression was upregulated in DRG tissues derived from lumbar disc herniation (LDH) model rats. In addition, DRG cells from LDH rats exhibited increased apoptosis compared with control rats. CDMP1 overexpression enhanced the cell viability of inflammatory cytokine‑induced DRG cells, and suppressed the apoptosis of inflammatory cytokine‑induced DRG cells via regulating the expression levels of Caspase‑3/8/9, BCL2 apoptosis regulator, and BCL2 associated X. Furthermore, CDMP1 overexpression was demonstrated to affect the Wnt/β‑Catenin pathway in the inflammatory cytokine‑induced DRG cells. In conclusion, the present findings suggested that CDMP1 overexpression mediated inflammatory cytokine‑induced apoptosis via Wnt/β‑Catenin signaling in rat DRG cells.

Aims Osteosarcoma is the most frequent primary malignant bone tumor in children and adolescents. Identifying specific and sensitive biomarkers is beneficial to early detection and improvement of life qualities and overall survival rates of osteosarcoma patients. Materials and methods Realtime PCR was used to detect the expression of miR-598. CCK-8 assay was employed to detect the proliferation of osteosarcoma cells, while transwell assays were used to examine the migration and invasion. Tumor xenograft experiments were performed to test the in vivo malignancy of osteosarcoma cells. Co-culture experiment was used to study the relationship between osteosarcoma cells and osteoblast. Realtime PCR, Western Blotting and luciferase report assays were conducted for the target genes analysis. Key findings Using a cohort of 20 cases of osteosarcoma and paired adjacent tissue samples, we found that miR-598 expression was decreased in osteosarcoma tissues and serum, as well as the osteosarcoma cell lines. Over expression of miR-598 suppressed the proliferation, migration, and invasion of osteosarcoma cells, while inhibition of miR-598 expression stimulated the proliferation, migration, and invasion. However, MiR-598 had no effect on osteosarcoma cell apoptosis. Data from nude mice further demonstrated the inhibitory role of miR-598 in osteosarcoma progression in vivo. Mechanically, miR-598 played its role by modulating osteoblastic differentiation in the microenvironment and targeting PDGFB and MET. Significance Our findings enrich the knowledge of miR-598 in osteosarcoma progression, and reveal miR-598 as a promising diagnostic, prognostic, therapeutic biomarker for osteosarcoma.

Objectives Due to recent developments and the wide application of percutaneous transforaminal discectomy (PTED) in China, we herein compare its clinical effects with microendoscopic discectomy (MED) for the treatment of lumbar disc herniation in terms of recurrence and revision rates. Methods Six databases, namely, PubMed, EMBASE, Cochrane Library, Ovid, China National Knowledge Infrastructure and Wanfang, were searched by computer. The literature was screened according to inclusion and exclusion criteria, and the quality of the included literature was evaluated. After extracting the data from the papers, Review Manager 5.2 software (Cochrane Collaboration, Oxford, UK) was applied to analyze these data. Finally, sensitivity and publication bias analyses of the results were conducted. Results A total of 12 studies consisting of 2400 patients were included in this meta-analysis. A comparison of PTED with MED revealed higher postoperative recurrence and postoperative revision rates for PTED (odds ratio [OR] recurrence, 1.60; 95% confidence interval [CI], 1.01 to 2.53; p=0.05 and OR revision, 1.77; 95% CI, 1.18 to 2.64, p=0.006). Conclusion PTED has a number of advantages because it is a minimally invasive surgery, but its recurrence and revision rates are higher than MED. Therefore, MED should not be completely replaced by PTED.

The present study aimed to explore miR-125 effects on rheumatoid arthritis (RA) development to provide a potential target for RA. Briefly, rat RA model was established (Model group) by injection of Freund’s Complete Adjuvant into the left hind toe. Normal rats injected with saline in the same location were set as Normal group. All rats’ secondary foot swelling degree, polyarthritis index score, spleen and thymus index were measured. Synovial tissues were subjected to Hematoxylin–Eosin (HE) staining and immunohistochemistry. Synovial cells of each group were isolated and named as Normal-C group and Model-C group, respectively. Synovial cells of Model-C group further underwent cotransfection with miR-125 mimics and PARP2-siRNA (mimics+siPARP2 group) or with miR-125 negative control (NC) and PARP2-siRNA NC (NC group). Quantitative reverse transcriptase PCR (qRT-PCR), Western blot, luciferase reporter assay, ELISA, and MTT assay were performed. As a result, compared with Normal group, rats of Model group showed significantly higher secondary foot swelling degree, polyarthritis index score, spleen and thymus index (P

Figure S1. HMGB1 was overexpressed in RA synovial tissue compared with OA tissue. (DOCX 488 kb)

Table S1. Sequences of oligonucleotides. (DOCX 12 kb)

Background Studies have investigated the correlation between tumor necrosis factor related apoptosis-inducing ligand (TRAIL) gene polymorphisms and the susceptibility and severity of intervertebral disc degeneration (IDD), but the results were inconsistent. To evaluate the specific relationship, we performed a meta-analysis to clarify the controversies. Methods Four databases were searched, and the pooled results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Results Three case-control studies from Han Chinese were included (565 cases and 427 controls). All the included studies reported TRAIL 1595C/T gene polymorphisms. The recessive model (CC vs. CT + TT) was the optimal model, which demonstrated a significant relationship between 1595C/T polymorphisms and increased IDD risk (OR = 2.18, 1.45 to 3.27, P = 0.000). No significant heterogeneity was found in the recessive model (I2 = 48.6%, P = 0.143). Patients with lower grade IDD had more genotypes or alleles including 1595TT genotype (grade II vs. grade III: OR = 2.12, 1.18 to 3.83, P = 0.012; grade III vs. grade IV: OR = 2.59, 1.29 to 5.22, P = 0.007) and 1595 T allele (grade II vs. grade III: OR = 1.91, 1.43 to 2.55, P = 0.000; grade II vs. grade IV: OR = 2.46, 0.94 to 1.76, P = 0.000). Conclusions There is a significant relationship between 1595C/T polymorphisms and the susceptibility and severity of IDD in Han Chinese. Patients with lower grade IDD had higher frequency of the 1595TT genotype and 1595 T allele. Electronic supplementary material The online version of this article (doi: 10.1186/s12891-017-1916-3) contains supplementary material, which is available to authorized users.

Objective To compare the effectiveness of allograft and iliac crest autograft in atlantoaxial fusion. Patients and Methods Between January 2012 and December 2012, 41 consecutive patients underwent posterior atlantoaxial fusion with a screw-rod fixation system in our spine center. The choice to use allograft or iliac crest autograft was made by the patient himself or herself after being informed about the advantages and disadvantages of both methods. In the allograft group, we used mixed material of morcellized demineralized freeze-dried bone allograft and local autograft for posterior atlantoaxial fusion. In the autograft group, we used the morcellized iliac crest autograft for fusion. Patients underwent regular follow up including CT scans and dynamic radiographs 6 months postoperatively and every 6 months thereafter until study completion or confirmation of fusion. Results Twenty-four patients underwent posterior atlantoaxial fusion with allograft, and 17 underwent fusion with autograft. All patients were followed up for at least 24 months. At the final follow-up visit, only two (8.3%) patients in the allograft group had confirmed posterior bony fusion on CT imaging while 15 (88.2%) patients in the autograft group had confirmed posterior bony fusion. None of the 41 patients had movement on the dynamic radiographs. Conclusions Allograft is not reliable for posterior atlantoaxial fusion even with the rigid internal fixation of modern constructs. Autograft remains the first choice for atlantoaxial fusion despite the donor-site morbidity. The assessment of fusion based on a lack of movement on dynamic radiographs is not reliable. The confirmation of fusion should be based on the presence of bridging bone on CT imaging.

Dear Editor Chronic lower back pain (CLBP) is one of the most common musculoskeletal disorders in modern society which seriously impacts the people's daily life ⇓. Approximately 70–85% people suffer lower back pain (LBP) at some point in their lives ⇓. The recently global review of the prevalence of LBP in the adult general population was published in 2000 and showed point prevalence of 12–33% and 1-year prevalence of 22–65% ⇓. Massage which is perceived as a safe therapeutic modality without any significant risks or side effects is widely used in the treatment of CLBP ⇓. It is defined as a manipulation using the hands or a mechanical device, in which numerous specific and general techniques are used in sequence, such as effleurage, petrissage, and percussion. The mechanic of Massage therapy include: local vasodilation and increase blood and lymph circulation to improve the nutritional status of local organs; deep tissue blood flow to the surface or reduced blood flow …

The aims of this systematic review were to study the analgesic effect of real acupuncture and to explore whether sham acupuncture (SA) type is related to the estimated effect of real acupuncture for musculoskeletal pain. Five databases were searched. The outcome was pain or disability immediately (≤1 week) following an intervention. Standardized mean differences (SMDs) with 95% confidence intervals were calculated. Meta-regression was used to explore possible sources of heterogeneity. Sixty-three studies (6382 individuals) were included. Eight condition types were included. The pooled effect size was moderate for pain relief (59 trials, 4980 individuals, SMD −0.61, 95% CI −0.76 to −0.47; P

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children; some clinical trials have reported the effects of total glucosides of peony (TGP) in the treatment of JIA. However, no systematic review has yet been conducted. In this study, we assessed the efficacy and safety in patients with JIA enrolled in randomized controlled trials (RCTs) of TGP. We extracted data for studies searched from 8 electronic databases that were searched and also evaluated the methodological quality of the included studies. We assessed the following outcome measures: overall response rate, pain, tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness (DMS), grip strength (GS), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse effects (AEs) in short term (4–8 weeks), intermediate term (9–26 weeks), and long term (>26 weeks). The final analysis showed that TGP acted as a unique nonbiologic disease-modifying antirheumatic drug (nonbiologic DMARD), and its therapeutic effects were safe and efficacious for the treatment of JIA with few AEs. However, more high-quality RCTs are needed to confirm these therapeutic effects.

The aims of this systematic review were to study the analgesic effect of real acupuncture and to explore whether sham acupuncture (SA) type is related to the estimated effect of real acupuncture for musculoskeletal pain. Five databases were searched. The outcome was pain or disability immediately (≤1 week) following an intervention. Standardized mean differences (SMDs) with 95 % confidence intervals were calculated. Meta-regression was used to explore possible sources of heterogeneity. Sixty-three studies (6382 individuals) were included. Eight condition types were included. The pooled effect size was moderate for pain relief (59 trials, 4,980 individuals, SMD −0.61, 95 % CI −0.76 to −0.47; P P

Background Neck pain (NP) and low back pain (LBP) are common symptoms bothering people in daily life. Traditional Chinese medicine (TCM) has been used to treat various symptoms and diseases in China and has been demonstrated to be effective. The objective of the present study was to review and analyze the existing data about pain and disability in TCM treatments for NP and LBP. Methods Studies were identified by a comprehensive search of databases, such as MEDLINE, EMBASE, and Cochrane Library, up to September 1, 2013. A meta-analysis was performed to evaluate the efficacy and safety of TCM in managing NP and LBP. Results Seventy five randomized controlled trials (n = 11077) were included. Almost all of the studies investigated individuals experiencing chronic NP (CNP) or chronic LBP (CLBP). We found moderate evidence that acupuncture was more effective than sham-acupuncture in reducing pain immediately post-treatment for CNP (visual analogue scale (VAS) 10 cm, mean difference (MD) = -0.58 (-0.94, -0.22), 95% confidence interval, p = 0.01), CLBP (standardized mean difference = -0.47 (-0.77, -0.17), p = 0.003), and acute LBP (VAS 10 cm, MD = -0.99 (-1.24, -0.73), p< 0.001). Cupping could be more effective than waitlist in VAS (100 mm) (MD = -19.10 (-27.61, -10.58), p < 0. 001) for CNP or medications (e.g. NSAID) for CLBP (MD = -5.4 (-8.9, -0.19), p = 0.003). No serious or life-threatening adverse effects were found. Conclusions Acupuncture, acupressure, and cupping could be efficacious in treating the pain and disability associated with CNP or CLBP in the immediate term. Gua sha, tai chi, qigong, and Chinese manipulation showed fair effects, but we were unable to draw any definite conclusions, and further research is still needed. The efficacy of tuina and moxibustion is unknown because no direct evidence was obtained. These TCM modalities are relatively safe.