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Background Osteosarcoma (OS) is a highly malignant tumor. Improving chemotherapeutic resistance is very important to improve the survival rate of OS. Exosomes and microRNAs (MiRNA) play important roles in the mechanism of chemotherapeutic resistance transmission. More and more researches focus the mechanism of miRNAs carried by exosomes in the transmission of chemotherapeutic resistance of OS. This study focused on exploring the mechanism of exosomal miR-331 in the transmission of chemoresistance in OS. Methods We cultured OS drug-resistant cells and extracted exosomes of these cells. The secretion and uptake of exosomes in OS drug-resistant cells and OS cells (OSCs) were confirmed by fluorescence tracking assay and transwell experiments. The differential expression of microRNA-331 (miR-331) in exosomes of OS resistant and OS cells was investigated by RT-PCR. The effects of drug-resistant exosomes on proliferation and migration of OS cells were determined by MTT assay and scratches assay. MDC staining, RT-PCR, and Western blot were used to detect the role of autophagy which regulated by drug-resistant cell-derived exosom-miR-331. Results We found that the expression difference of miR-331 between drug-resistant cells of MG63 and HOS cell lines and tumor cells was the most significant. Drug resistant OSCs secreted exosomes and were ingested by OSCs, which then promoted OSCs to acquire drug resistance. In addition, exosomes secreted by drug-resistant OSCs promote drug resistance by carrying miRNAs. Interestingly, inhibition of miRNA resulted in reduced drug resistance transmission of exosomes. Finally, we found that the exosomes secreted by drug-resistant OSCs could induce autophagy of OSCs by carrying miR-331, thus making OSCs acquire drug resistance. Inhibition of miR-331 can effectively improve drug resistance of OSCs. Conclusions Chemoresistant OSCs-derived exosomes promote the transmission of drug resistance by carrying miR-331 and inducing autophagy. Inhibition of miR-331 could effectively alleviate drug resistance of OSCs.

Background The standard treatment for severe displaced pediatric supracondylar humeral fracture (SCHF) is closed reduction and percutaneous pin fixation. However, controversy persists concerning the optimal pin fixation technique. The purpose of this study was to compare the safety and efficacy on the configuration of lateral entry only with crossed entry pin fixation for SCHF, including Gartland type II and type III fractures in children. Methods Published literatures, including retrospective studies, prospective studies, and randomized controlled trials, presenting the probability of poor functional consequence of elbow and/or loss of reduction and/or iatrogenic ulnar nerve injury and/or superficial infection and/or cubitus varus were included. Statistical analysis was performed with the Review Manager 5.3 software. Results Twenty-four studies were included in the present meta-analysis involving 1163 patients with lateral entry pins and 1059 patients with crossed entry pins. An excellent score of Flynn criteria occurred more commonly in patients who treated with crossed pins than in patients with lateral pins only (RR = 0.93; 95% CI 0.87–0.99; P = 0.03). In accordance with previous systematic review, the incidence of iatrogenic ulnar nerve injury in crossed entry group was significantly more than in lateral entry group with statistical difference (RR = 0.26; 95% CI 0.14–0.47; P

// Yuyan Na 1,2,* , Rui Bai 1,* , Zhenqun Zhao 1 , Yishan Wei 1 , Daihe Li 1 , Yong Wang 1 , Chao Sun 1 , Liang Sun 1 , Bolun Zhang 1,2 , Tianbo Jin 3,4 and Wanlin Liu 1 1 Department of Pediatric Orthopedics, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China 2 Graduate School of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, China 3 Xi’an Tiangen Precision Medical Institute, Xi’an, Shaanxi, China 4 National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi’an, Shaanxi, China * These authors have contributed equally to this work Correspondence to: Wanlin Liu, email: // Tianbo Jin, email: // Keywords : knee OA; IL1R1; genetic polymorphism; case-control study Received : August 11, 2016 Accepted : December 07, 2016 Published : December 14, 2016 Abstract IL1R1 , encoding interleukin 1 receptor type 1, is located in the IL-1 gene cluster and is involved in the pathogenesis of hand, hip, and knee osteoarthritis (OA) in different ethnicities. However, the link between IL1R1 polymorphisms and OA risk in the Chinese Han population is unknown. We studied the association between five IL1R1 polymorphisms (rs10490571, rs12712127, rs956730, rs3917225, and rs3917318) and OA risk by analyzing the genotypes of 298 knee OA patients and 297 controls using Sequenom MassARRAY technology. Logistic regression analysis after adjusting for gender and age revealed significant differences in the allele frequencies of IL1R1 rs956730 and IL1R1 rs3917225 between patients and controls. In addition, IL1R1 rs3917225 was associated with increased risk of knee OA with or without adjustment by age and gender in the dominant model (adjusted OR= 1.47, 95%CI: 1.04-2.07, P = 0.030), the recessive model (adjusted OR= 1.75, 95%CI: 1.08-2.85, P = 0.023), and the additive model (adjusted OR= 1.40, 95%CI: 1.09-1.79, P = 0.007). This study is the first to report that IL1R1 polymorphisms are associated with knee OA susceptibility in the Northwestern Chinese Han population.

Ankylosing spondylitis (AS) is an extreme form of inflammatory arthritis which always leads to bony fusion of vertebral and chronic pain of back. A lot of genes including interleukin, matrix metalloproteinases (MMPs), and endoplasmic reticulum aminopeptidase were found associated with AS. MMP family members were involved in the autoimmune disease and orthopedic diseases such as rheumatoid arthritis and osteoarthritis, while few studies concentrated on the correlation between single-nucleotide polymorphisms (SNPs) in MMP and AS. In addition, there is no report on the relationship between MMP-8 and AS. To investigate the association between SNPs in MMP-8 and AS, we recruited 268 patients with AS and 654 healthy people to conduct a case–control study. Five SNPs including rs3740938, rs2012390, rs1940475, rs11225394, and rs11225395 of MMP-8 gene were genotyped. It was found rs3740938 of MMP-8 was associated with an increased risk of AS under the dominant model and additive model after adjustment for gender and age by performing logistic regression analysis (odds ratio [OR] = 1.49, 95% confidence interval [CI] = 1.02–2.18, P = .038; OR = 1.37, 95% CI = 1.01–1.87, P = .042, respectively). Moreover, haplotype “GGTCA” was associated with an increased risk of AS without adjustment for age and gender (OR = 1.75, 95% CI = 1.05–2.92, P = .032), while no positive result was found after adjustment for age and gender. Based on our results, our study indicates significant association between SNPs of MMP-8 and AS risk in a Chinese Han population and these results provide the first evidence that MMP-8 is correlated with AS.

Cytovillin plays structural and regulatory roles in the assembly and stabilization of specialized plasma membrane domains and in the tumor angiogenesis. Cytovillin expression has been proposed to be an effective biomarker of prognosis in patients with osteosarcoma, and many studies have been performed to assess the prognostic role of cytovillin expression in patients with osteosarcoma. We performed this meta-analysis to provide a comprehensive evaluation of the role of cytovillin expression on the overall survival rate by calculating the pooled risk ratio (RR) with corresponding 95 % confidence interval (95 % CI). Finally, eight studies with a total of 415 patients with osteosarcoma were included into the meta-analysis. Meta-analysis of total eight studies showed that cytovillin expression was obviously associated with lower overall survival rate in patients with osteosarcoma (RR = 0.41, 95 % CI 0.28–0.58, P

Many studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and risk of fractures, but the impact of MTHFR polymorphisms on fractures risk is unclear owing to the obvious inconsistence among those studies. This study aims to quantify the strength of association between MTHFR C677T and A1298C polymorphisms and risk of fractures. We searched the PubMed, Embase and Wanfang databases for articles relating the association between MTHFR C677T and A1298C polymorphisms and risk of fractures in humans. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess the associations. Meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of any site fractures (for T vs. C, OR = 1.17, 95 % CI 1.03-1.32; for TT vs. CC, OR = 1. 31, 95 % CI 1.11-1.54; for TT vs. CT, OR = 1.22, 95 % CI 1.04-1.43; for TT vs. CT/CC, OR = 1.31, 95 % CI 1.13-1.51). Besides, MTHFR A1298C polymorphism was also associated with increased risk of any site fractures. Subgroup meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of vertebral fractures under three genetic contrast modes (for TT vs. CC, OR = 1.43, 95 % CI 1.05-1.95; for TT vs. CT, OR = 1.36, 95 % CI 1.01-1.85; for TT vs. CT/CC, OR = 1.50, 95 % CI 1.17-1.91), but there was no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures (all P values were more than 0.05). Thus, individuals with homozygote genotype TT of MTHFR C677T have obviously increased risk of vertebral fractures compared those with heterozygote genotype CT or homozygote genotype CC. There is no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures.

Osteonecrosis of the femoral head (ONFH) is a common hip joint disease, and steroid-induced ONFH accounts for a large number of cases. Here, we examined eight previously-identified single-nucleotide polymorphisms (SNPs) in the MPP2 and MPP9 genes of 285 steroid-induced ONFH patients and 507 healthy controls from northern China to determine whether these SNPs were associated with the risk of developing steroid-induced ONFH. Chi-squared tests and genetic model and haplotype analyses were used to evaluate associations. The rs2274755 SNP in MMP9 was associated with a decreased risk of steroid-induced ONFH in the allele, dominant, and additive models. Additionally, the "CGC" MMP9 haplotype was associated with a 0.69-fold decrease in the risk of steroid-induced ONFH. Although additional, larger population-based studies are needed to confirm these findings, our results reveal for the first time an association between a MMP9 SNP at the rs2274755 locus and a decreased risk of steroid-induced ONFH in a northern Chinese population.

An animal model of steroid-induced avascular necrosis of femoral head (SANFH) was established to investigate the role of oxidative DNA damage of bone marrow hematopoietic cells in SANFH. Forty-five-month-old Japanese white rabbits (male or female, 2.5 ± 0.5 kg) were randomly divided into groups A (methylprednisolone + Escherichia coli endotoxin), B (methylprednisolone alone), C (E. coli endotoxin alone), and D (blank control). The animals were sacrificed two and four weeks after administration of the last dose (N = 5 each group and each time). Left and right femoral heads were fixed and decalcified. Empty lacunae were counted by hematoxylin and eosin staining and oxidative DNA damage of bone marrow hematopoietic cells was detected by immunohistochemistry. At week 2, the rate of oxidative DNA damage in bone marrow hematopoietic cells was significantly higher in group A than in groups B, C, and D (P < 0.01), while there was no significant difference between groups B, C, and D. At week 4, the rate of oxidative DNA damage in bone marrow hematopoietic cells was significantly higher in group A than in groups B, C, and D (P < 0.01), while there was no significant difference among groups B, C, and D. Thus, oxidative DNA damage of bone marrow hematopoietic cells appears to play an important role in SANFH.

Although classified as benign, giant cell tumors of the bone (GCTB) may be aggressive, recur and even metastasize to the lungs. In addition, the pathogenesis and histogenesis remain unclear; thus, the driving factors behind the strong tumor growth capacity of GCTB require investigation. In the present study, the expression levels of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF), which are promoted by hypoxic conditions, were determined in 22 sacral GCTB samples using immunohistochemistry and western blot analysis. Furthermore, CD34 expression was analyzed using these methods. The correlation between HIF-1α or VEGF expression and the tumor microvessel density (MVD) was then determined. The results demonstrated that HIF-1α, VEGF and CD34 were overexpressed in the 22 sacral GCTB specimens, and overexpression of HIF-1α and VEGF correlated with the tumor MVD. Thus, the present study has provided novel indicators for the tumor growth capacity of GCTBs.