To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.

MicroRNAs (miRNAs) play a key role in the regulation of almost all the physiological and pathological processes, including bone metabolism. Recent studies have suggested that miR-27 might play a key role in osteoblast differentiation and bone formation. Increasing evidence indicates that the canonical Wnt signaling pathway contributes to different stages of bone formation. In this study, we identify miR-27a can promote osteoblast differentiation by repressing a new target, secreted frizzled-related proteins 1 (sFRP1) expression at the transcriptional level. Here, 21 candidate targets of miR-27a involved in canonical Wnt/β-catenin signaling were predicted, and a significant decrease in sFRP1 luciferase activity was observed both in 293T and MG63 cells co-transfected with the matched luciferase reporter constructs and miR-27a mimic. Furthermore, the presence of exogenous miR-27a significantly decreased sFRP1 mRNA and protein expression in hFOB1.19 cells during both proliferation and osteogenic differentiation. The over-expression of miR-27a or knockdown sFRP1 significantly increased the percentage of apoptotic hFOBs, the percentage of cells in the G2-M phase of the cell cycle and the expression of key osteoblastic markers, including ALP, SPP1, RUNX2 and ALP activity. Over-expression of miR-27a or knockdown of endogenous sFRP1 led to an accumulation of β-catenin in hFOBs. In the present study, we demonstrate that miR-27a induced gene silencing effect is a vital mechanism contributing to bone metabolism in hFOB cells in vitro, which is partly affected by the post-transcriptional regulation of sFRP1, during osteoblast proliferation, apoptosis and differentiation.

The objective of this study was to investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in ankylosing spondylitis (AS) patients. IL-23 and IL-17 levels in the serum and supernatants of cultured peripheral blood mononuclear cells (PBMCs) were determined by ELISA. IL-23p19 mRNA expression in PBMCs were analyzed using RT-PCR. The patients with AS at active stage showed elevated levels of IL-23 and IL-17 in the serum and supernatants of cultured PBMCs. A higher expression of IL-23p19 mRNA in PBMCs of AS patients was also observed. A significantly enhanced production of IL-17 in the supernatants of cultured PBMCs was found in the presence of recombinant IL-23 and this effect was more significant in patients with AS. The results suggest that IL-23 and IL-17 may play critical roles in the pathogenesis of AS and IL-23-stimulated production of IL-17 by PBMCs may be responsible for the development of AS.

Objective Vaccines including pneumococcal and influenza vaccines are recommended in patients with immunosuppressive treatment. However, vaccine coverage remains extremely low. Our study was to investigate vaccination uptake, knowledge, attitude and practice (KAP) towards certain vaccinations among these patients, and to identify the factors influencing willingness to be vaccinated. Methods A cross-sectional survey was conducted among patients with rheumatic diseases in a tertiary hospital in China. Baseline assessments were completed by using questionnaires including vaccination uptake and KAP towards certain infections and vaccinations. Results 235 patients completed the study. Mean age was 39.69 years old, while 66.4% were females. Only 6.4% of the participants once had taken vaccine in recent five years. One patient had influenza vaccination, and none ever took pneumococcal vaccine. 3.8% had doctor's recommendation on taking influenza, pneumococcal or herpes zoster vaccine. Major reasons given for not being vaccinated included "unnecessary" (8.9%) and "troublesome to take vaccines" (8.5%). Patients would take influenza or pneumococcal vaccines if they had heard of them before, had knowledge of infection, and had belief in vaccine's safety and reliability (p < 0.05). Conclusion Vaccine coverage among people with rheumatic diseases was low in China. Methods to improve KAP toward infections and vaccinations should be taken.

Objective Gout is the most common inflammatory arthritis and the worldwide incidence is increasing. By revealing the metabolic alterations in serum and urine of gout patients, the first aim of our study was to discover novel molecular biomarkers allowing for early diagnosis. We also aimed to investigate the underlying pathogenic pathways. Methods Serum and urine samples from gout patients (n = 30) and age-matched healthy controls (n = 30) were analysed by ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) to screen the differential metabolites and construct a diagnostic model. Next, the model was verified and optimized in the second validation cohort (n = 100). The pathways were illustrated to understand the underlying pathogenesis of gout. Results In general, serum metabolomics demonstrated a clearer distinction than urine metabolomics. In the discovery cohort, 40 differential serum metabolites were identified that could distinguish gout patients from healthy controls. Among them, eight serum metabolites were verified in the validation cohort. Through regression analysis, the final model consisted of three serum metabolites—pyroglutamic acid, 2-methylbutyryl carnitine and Phe-Phe—that presented optimal diagnostic power. The three proposed metabolites produced an area under the curve of 0.956 (95% CI 0.911, 1.000). Additionally, the proposed metabolic pathways were primarily involved in purine metabolism, branched-chain amino acids (BCAAs) metabolism, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, bile secretion and arachidonic acid metabolism. Conclusion The metabolomics signatures could serve as an efficient tool for early diagnosis and provide novel insights into the pathogenesis of gout.