Tauroursodeoxycholic acid suppresses biliary epithelial cell apoptosis and endoplasmic reticulum stress by miR-107/NCK1 axis in a FXR-dependent manner.

Tauroursodeoxycholic acid (TUDCA) can activate farnesoid X receptor (FXR) to involve in the formation of gallstones. Here, this study aimed to probe the potential mechanism of TUDCA-FXR network in the formation of bile duct stone. The levels of TUDCA, FXR and NCK1 were decreased, while the level of miR-107 was increased in the serum of bile duct stone patients. FXR expression was positively correlated with TUDCA or NCK1 expression in patients, moreover, TUDCA pretreatment in biliary epithelial cells increased the levels of FXR and NCK1, and rescued the decrease of NCK1 caused by FXR knockdown in cells. Then functional analysis showed FXR knockdown caused apoptosis and endoplasmic reticulum stress (ERS) as well as suppressed proliferation in biliary epithelial cells in vitro, which were attenuated by TUDCA pretreatment or NCK1 overexpression Mechanistically, NCK1 was a target of miR-107, which was up-regulated by FXR silencing, and FXR knockdown-induced decrease of NCK1 was rescued by miR-107 inhibition. Additionally, miR-107 expression was negatively correlated with TUDCA expression in bile duct stone patients, and TUDCA pretreatment in biliary epithelial cells decreased miR-107 expression by FXR. Functionally, the pretreatment of TUDCA or FXR agonist suppressed miR-107-evoked apoptosis and ERS in biliary epithelial cells. In conclusion, TUDCA up-regulates FXR expression to activate NCK1 through absorbing miR-107, thus suppressing the apoptosis and ERS in biliary epithelial cells, these results provided a theoretical basis for elucidating the mechanism of bile duct stone formation.

RIOK3 potentially regulates osteogenesis-related pathways in ankylosing spondylitis and the differentiation of bone marrow mesenchymal stem cells.

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.

A novel privacy-preserving federated genome-wide association study framework and its application in identifying potential risk variants in ankylosing spondylitis.

Genome-wide association studies (GWAS) have been widely used for identifying potential risk variants in various diseases. A statistically meaningful GWAS typically requires a large sample size to detect disease-associated single nucleotide polymorphisms (SNPs). However, a single institution usually only possesses a limited number of samples. Therefore, cross-institutional partnerships are required to increase sample size and statistical power. However, cross-institutional partnerships offer significant challenges, a major one being data privacy. For example, the privacy awareness of people, the impact of data privacy leakages and the privacy-related risks are becoming increasingly important, while there is no de-identification standard available to safeguard genomic data sharing. In this paper, we introduce a novel privacy-preserving federated GWAS framework (iPRIVATES). Equipped with privacy-preserving federated analysis, iPRIVATES enables multiple institutions to jointly perform GWAS analysis without leaking patient-level genotyping data. Only aggregated local statistics are exchanged within the study network. In addition, we evaluate the performance of iPRIVATES through both simulated data and a real-world application for identifying potential risk variants in ankylosing spondylitis (AS). The experimental results showed that the strongest signal of AS-associated SNPs reside mostly around the human leukocyte antigen (HLA) regions. The proposed iPRIVATES framework achieved equivalent results as traditional centralized implementation, demonstrating its great potential in driving collaborative genomic research for different diseases while preserving data privacy.

Polysaccharide-Based Injectable Hydrogels with Fast Gelation and Self-Strengthening Mechanical Kinetics for Oral Tissue Regeneration.

Oral defects lead to a series of function disorders, severely threatening the patients' health. Although injectable hydrogels are widely studied in tissue regeneration, their mechanical performance is usually stationary after implant, without further self-adaption toward the microenvironment. Herein, an injectable hydrogel with programmed mechanical kinetics of instant gelation and gradual self-strengthening along with outstanding biodegradation ability is developed. The fast gelation is realized through rapid Schiff base reaction between biodegradable chitosan and aldehyde-modified sodium hyaluronate, while self-strengthening is achieved via slow reaction between redundant amino groups on chitosan and epoxy-modified hydroxyapatite. The resultant hydrogel also possesses multiple functions including (1) bio-adhesion, (2) self-healing, (3) bactericidal, (4) hemostasis, and (5) X-ray in situ imaging, which can be effectively used for oral jaw repair. We believe that the strategy illustrated here will provide new insights into dynamic mechanical regulation of injectable hydrogels and promote their application in tissue regeneration.

Frailty predicts knee pain trajectory over 9 years: results from the Osteoarthritis Initiative.

OBJECTIVE: Frailty is a multisystem syndrome and its relationship with symptomatic osteoarthritis has been reported. We aimed to identify trajectories of knee pain in a large prospective cohort and to describe the effect of frailty status at baseline on the pain trajectories over 9 years. METHODS: We included 4419 participants (mean age 61.3 years, 58% female) from the Osteoarthritis Initiative cohort. Participants were classified as "no frailty," "pre-frailty," or "frailty" at baseline, based on 5 characteristics (ie, unintentional weight loss, exhaustion, weak energy, slow gait speed, and low physical activity). Knee pain was evaluated annually using the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (0-20) from baseline to 9 years. RESULTS: Of the participants included, 38.4%, 55.4%, and 6.3% were classified as "no frailty," "pre-frailty," and "frailty," respectively. Five pain trajectories were identified: "No pain" (n = 1010, 22.8%), "Mild pain" (n = 1656, 37.3%), "Moderate pain" (n = 1149, 26.0%), "Severe pain" (n = 477, 10.9%), and "Very Severe pain" (n = 127, 3.0%). Compared to participants with no frailty, those with pre-frailty and frailty were more likely to have more severe pain trajectories (pre-frailty: odds ratios [ORs] 1.5 to 2.1; frailty: ORs 1.5 to 5.0), after adjusting for potential confounders. Further analyses indicated that the associations between frailty and pain were mainly driven by exhaustion, slow gait speed, and weak energy. CONCLUSIONS: Approximately two-thirds of middle-aged and older adults were frail or pre-frail. The role of frailty in predicting pain trajectories suggests that frailty may be an important treatment target for knee pain.

WWP2 overexpression inhibits the antitumor effects of doxorubicin in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common liver cancer that accounts for 90% of cases. Doxorubicin exhibits a broad spectrum of antitumor activity and is one of the most active agents in HCC. WW domain-containing protein 2 (WWP2) is highly expressed in HCC tissues and activates protein kinase B (AKT) signaling pathway to enhance tumor metastasis. However, the role of WWP2 in the glycolysis and antitumor effects of doxorubicin and the epigenetic alterations of WWP2 in HCC remain to be elucidated. The levels of WWP2 and N6-methyladenosine methyltransferase-like 3 (METTL3) in clinical samples and cells were investigated. WWP2 were silenced or overexpressed to study the role of WWP2 in regulating cell proliferation, colony formation, and glycolysis. RNA immunoprecipitation was performed to test m6 A levels. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot were used to measure mRNA and protein, respectively. WWP2 silencing inhibits cell proliferation, colony formation, and glycolysis, while WWP2 overexpression has the inverse effects via the AKT signaling pathway. Silencing WWP2 enhances doxorubicin's antitumor effect, while WWP2 overexpression suppresses doxorubicin's antitumor effect. Data also support that METTL3 mediates WWP2 m6A modification, and m6A reader, IGF2BP2, binds to the methylated WWP2 to promote the stability of WWP2, leading to upregulation of WWP2. METTL3 mediates WWP2 m6A modification, which can be recognized and bound by IGF2BP2 to increase the stability of WWP2, leading to WWP2 overexpression which inhibits the antitumor effects of doxorubicin through METTL3/WWP2/AKT/glycolysis axis.

DNA Methylation and mRNA Expression of B7-H3 Gene in Ankylosing Spondylitis: A Case-Control Study.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory arthritis, with a high prevalence in patients in their mid-20s. Its pathogenesis is not well understood; however, genetic factors likely play a critical role. Epigenetic DNA changes may be involved in the pathogenesis of AS. In this study, we explored the methylation and transcription levels of the B7-H3 gene and its association with AS in an eastern Chinese Han population. METHODS: Peripheral blood of AS patients and healthy controls was used to extract genomic DNA and B7-H3 methylation levels were analyzed using sodium bisulfite followed by multiplex polymerase chain reaction. SPSS software was used to determine the statistical significance of the results. RESULTS: Hypomethylation of the promoter of the B7-H3 gene was observed in AS patients, whereas the B7-H3 gene expression was significantly enhanced in AS patients. CONCLUSION: Epigenetic modifications of B7-H3 were associated with susceptibility to AS. Hypomethylation of the B7-H3 promoter, which leads to B7-H3 overexpression, may be involved in the pathogenesis of AS.

The Expression Level of FOXO3a in Patients With Autoimmune Diseases: A Meta-analysis.

METHODS: PubMed, Web of Science, and China National Knowledge Infrastructure were used to retrieve relevant articles. The pooled standard mean difference with 95% confidence interval was calculated. RESULTS: Totally, 10 studies from 7 publications were included. The levels of FOXO3a were significantly decreased in patients with autoimmune diseases compared with healthy controls (standard mean difference, -1.045; 95% confidence interval, -1.892 to -0.197). When stratified by disease, FOXO3a levels were significantly decreased in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), but were significantly increased in systemic lupus erythematosus. FOXO3a levels of specific tissues or cells in patients with autoimmune diseases were significantly decreased, but no significant difference was observed in the subgroup of peripheral blood mononuclear cells. In the subgroup analysis combining disease and sample, significant differences of FOXO3a were observed in non-PMBCs of RA and IBD patients. CONCLUSIONS: Our study indicated that FOXO3a were significantly decreased in patients with autoimmune diseases. FOXO3a levels was a potential therapeutic target of autoimmune diseases.

Association of methylation level and transcript level in TRAF5 gene with ankylosing spondylitis: a case-control study.

To explore the association between methylation level and transcript level of TNF receptor-associated factor 5 (TRAF5) gene with ankylosing spondylitis (AS) in Chinese Han population. Methylation and mRNA expression level of the TRAF5 gene were tested in 98 patients and 98 healthy controls. Among the 21 CpG sites, methylation levels at eight sites were significantly different between AS patients and healthy controls. However, only three sites remained significantly different after the correction by the Benjamini-Hochberg method. Compared with controls, the CpG island of TRAF5 gene promoter was highly methylated in AS patients, and the relative mRNA expression level of TRAF5 was significantly reduced in AS patients. And the mRNA level was negatively correlated with the methylation level of TRAF5 gene in AS patients (rs = -0.453, P < 0.001). Subgroup analyses indicated that there was no significant difference in the level of methylation between groups of different status of HLA-B27 and medications in AS patients. Multiple linear regression showed that disease-modifying antirheumatic drugs could reduce methylation levels of AS patients after adjusting for the effects of other drugs. In conclusion, the hypermethylation of the TRAF5 might contribute to the pathogenesis of AS, but many open questions remain.

Serum Levels of Hepcidin in Rheumatoid Arthritis and Its Correlation with Disease Activity and Anemia: A Meta-analysis.

Present studies on serum hepcidin levels in patients with rheumatoid arthritis (RA) are inconsistent. We aimed to synthetically evaluate the relationship between hepcidin and RA, and the correlation of serum hepcidin levels and RA disease activity as well as anemia associated with RA. Multiple electronic databases were searched. Pooled standard mean difference (SMD) with 95% confidence interval (CI) and correlation coefficients between hepcidin levels and rheumatoid factor (RF), disease activity for 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) were calculated. Totally, 13 articles were available for this meta-analysis. The results revealed that serum levels of hepcidin were higher in RA patients compared to healthy controls (SMD = 0.573, 95% CI = 0.317 to 0.829, p < .001); RA patients with anemia had higher serum hepcidin levels than RA patients without anemia (SMD = 0.400, 95% CI = 0.080 to 0.720, p = .014); RA patients with pure ACD had higher serum hepcidin levels than RA patients with ACD and IDA (SMD = 0.658, 95% CI = 0.018 to 1.299, p = .044). Moreover, the result of correlation coefficients identified a significant positive correlation between hepcidin levels and RF, DAS28 as well as ESR. Serum hepcidin levels may be closely associated with the development of RA.

Interleukin-17 Gene Polymorphism (Rs2275913 G/A, Rs763780 C/T) in Rheumatoid arthritis：Meta-analysis Based on Ethnicity.

INTRODUCTION: The association between interleukin(IL)-17A and IL-17 F gene polymorphism with rheumatoid arthritis (RA) were inconsistent among previous studies. This meta-analysis aimed to determine the association between IL-17A and IL-17 F gene polymorphism with RA. METHODS: We searched Medline up to February 2020. Meta-analyses were performed for the comparisons of allele and multiple genetic models, including dominant, recessive, heterozygous, and homozygous models using fixed or random effects models. Odds ratios (OR) with 95% confidence intervals (95%CI) were utilized to assess the potential relationship. RESULTS: A total of 2315 confirmed cases and 2342 controls were included from eligible 10 case-controls studies. Meta analysis suggested that rs2275913 G allele increased the risk of RA in Caucasians (G vs A: OR = 1.14, 95% CI = 1.00-1.29, P = .044), but not in Mongolians (P > .05). Pooled analysis suggested that a significant associations between rs763780 C allele with RA susceptibility (C vs T: OR = 1.83, 95% CI = 1.13-2.97, P = .014). Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to RA risk in two races (P < .001). TSA plot revealed that the present study sufficient to draw a conclusion. CONCLUSIONS: This meta-analysis demonstrates IL-17A and IL-17 F genes play a significant role in RA, but its role in Mongolian populations needs further exploration.

BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis.

B cell activating factor of TNF family (BAFF) is a member of TNF ligand superfamily and plays a key role in B cell homeostasis, proliferation, maturation, and survival. In this study, we detected BAFF level, the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis (RA) patients and analyzed the correlation between BAFF level and clinical variables, laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA. A total of 50 RA patients and 50 healthy controls (HCs) were enrolled. We showed that the serum BAFF level in RA patients was significantly higher than that of HCs, and the percentages of B cell subsets (CD19+ B cells, CD19+CD27+ B cells, CD19+CD20+CD27+ B cells, and CD19+CD20-CD27+ B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19+BAFFR+ B cells, CD19+ BCMA+ B cells, and CD19+ TACI+ B cells in RA patients were significantly increased compared with those in HCs. The expression of important molecules in the NF-κB pathway (MKK3, MKK6, p-P38, p-P65, TRAF2, and p52) was significantly higher in RA patients than in HCs, but p100 level in RA patients was lower than that in HCs. The serum BAFF level was positively correlated with C-reactive protein, rheumatoid factor, disease activity score (in 28 joints), swollen joint counts, tender joint counts, and X-ray scores. When normal B cells were treated with BAFF in vitro, the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated. BAFF also promoted the expression of MKK3, MKK6, p-P38, p-P65, TRAF2, and p52. In conclusion, this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA. BAFF is involved in the differentiation, proliferation, and activation of B cells in RA through NF-κB signaling pathway, suggesting that BAFF might be an ideal therapeutic target for RA.

Red Cell Distribution Width and Mean Platelet Volume in Patients With Ankylosing Spondylitis: A Systematic Review and Meta-analysis.

OBJECTIVE: The results of previous studies regarding the relationship between red cell distribution width (RDW) or mean platelet volume (MPV) levels and ankylosing spondylitis (AS) are inconsistent. Therefore, we conducted this meta-analysis to systematically evaluate the associations. METHODS: The Web of Science, PubMed, and Cochrane Library (as of February 14, 2019) were used to retrieve relevant articles. Pooled standard mean difference (SMD) and its 95% confidence interval (CI) were calculated. All statistical analyses were performed using the "meta" and "metafor" packages of the R 3.5.1 software. RESULTS: Nine studies on RDW, including 775 AS patients and 972 healthy controls, and 8 studies on MPV, including 743 AS patients and 571 healthy controls, were included. The results showed that RDW levels were significantly higher in AS patients (SMD = 0.67; 95% CI, 0.30 to 1.05; p < 0.001) compared with healthy controls, whereas MPV levels (SMD = 0.01; 95% CI, -0.28 to 0.30; p = 0.929) were not significantly different from healthy controls. CONCLUSIONS: Our current study shows that the elevated levels of RDW may be associated with AS, whereas MPV levels may be not associated with AS.

Association between IL-17A and IL-17F gene polymorphism and susceptibility in inflammatory arthritis: A meta-analysis.

OBJECTIVES: The association between Interleukin (IL)-17A and IL-17F gene polymorphism with inflammatory arthritis were inconsistent among previous studies. This meta-analysis aimed to determine the association between IL-17A and IL-17F gene polymorphism with ankylosing spondylitis (AS), osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: We searched Medline up to August 2019. The summary Odds Ratio (OR) with corresponding 95% confidence intervals (CIs) was calculated to evaluate the relationship between IL-17A and IL-17F gene polymorphism with genetic susceptibility of AS, OA and RA. RESULTS: A total of 19 studies with 5298 cases and 5675 healthy controls were included. There were significant associations between rs2275913 G allele with OA, RA susceptibility (P < .05) but not AS. Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to AS and OA in Caucasian populations (P < .001) but not Mongolians. A significant association between rs763780 and RA susceptibility was detected in Caucasian populations (P < .05). CONCLUSION: IL-17F gene rs763780 C allele confers increased risk of inflammatory arthritis in Caucasians; IL-17A gene rs2275913 G allele are protective for OA susceptibility in Mongolians. More well-designed studies with larger sample size are needed to elucidate the role of IL-17A gene rs2275913 G allele in inflammatory arthritis, especially AS.

B7-H3: A promising therapeutic target for autoimmune diseases.

B7-H3 as a newly identified costimulatory molecule that belongs to B7 ligand family, is broadly expressed in both lymphoid and non-lymphoid tissues. The overexpression of B7-H3 has been verified to be correlated with the poor prognosis and poor clinical outcome of several human cancers. In recent years, researchers reveal that B7-H3 is involved in the pathogenesis of various autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), Sjögren's syndrome (SS), ankylosing spondylitis (AS), etc. In this review, we will discuss the biological function of B7-H3 and summarize the progress made over past years regarding its role in the occurrence and development of autoimmune diseases. The insights gained from these findings could serve as the foundation for future therapies of these diseases.

Hsp70 Gene Polymorphisms Are Associated With Disease Susceptibility and HRQOL Improvement in Chinese Han Population With Systemic Lupus Erythematosus.

OBJECTIVES: The aim of this study is to investigate whether heat shock protein 70 (Hsp70) gene polymorphisms are implicated in systemic lupus erythematous (SLE) susceptibility, the efficacy of glucocorticoids (GCs) treatment, and improvement of health-related quality of life. METHODS: A total of 499 SLE patients and 499 controls were included in a case-control study, and 468 SLE patients treated with GCs for 12 weeks were involved in a follow-up study. Patients who completed the 12-week follow-up were divided into GCs-sensitive and GCs-insensitive group by using the SLE disease activity index. The SF-36 was used to evaluate the health-related quality of life of SLE patients, and genotyping was performed by improved multiplex ligation detection reaction. RESULTS: rs2075800 was associated with SLE susceptibility (adjusted odds ratio [ORadj], 1.437; 95% confidence interval [CI], 1.113-1.855; Padj = 0.005; PBH = 0.020 by dominant model; ORadj, 1.602; 95% CI, 1.072-2.395; Padj = 0.022; PBH = 0.029 by TT vs CC model; ORadj = 1.396; 95% CI = 1.067-1.826; Padj = 0.015; PBH = 0.029 by TC vs CC model). In the follow-up study, rs2075799 was associated with the improvement in mental health (p = 0.004, PBH = 0.044), but we failed to find any association between the efficacy of GCs and Hsp70 gene polymorphisms. CONCLUSIONS: Hsp70 gene polymorphisms may be associated with susceptibility to SLE and improvement of mental health in Chinese Han population.

Neutrophil lymphocyte ratio in patients with ankylosing spondylitis: A systematic review and meta-analysis.

Objective: The aim of this meta-analysis was to investigate the association of neutrophil lymphocyte ratio (NLR) with AS (ankylosing spondylitis) patients.Methods: PubMed, Web of Science, Cochrane Library, Elsevier Science Direct and Google Scholar databases (up to 30 September 2018) were searched to collect all pertinent articles. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random effects model.Results: Totally 10 studies contained 765 AS patients and 701 healthy controls were included in our meta-analysis. The results indicated that there were significant statistical differences between AS patients and healthy controls in NLR (SMD = 0.418, 95%CI = 0.239-0.598, p < .001). Meanwhile, the results of subgroup analysis showed, in the subgroup of C-reactive protein (CRP) ≥10 and the two subgroups of BASDAI (the Bath AS Disease Activity Index), NLR levels in AS were significantly higher than in control (all p < .001). The results of subgroup analysis and meta-regression suggested that BASDAI and CRP were likely associated with NLR in AS patients.Conclusion: The current meta-analysis provides evidence that NLR is a reasonable measure to detect systemic inflammation in AS patients. Besides, NLR may be able to indicate disease activity in patients with AS.

Copy number variations and polymorphisms in HSP90AB1 and risk of systemic lupus erythematosus and efficacy of glucocorticoids.

The aim of our study was to assess the associations of HSP90AB1 copy number variations (CNVs) with systemic lupus erythematosus (SLE) risk and glucocorticoids (GCs) efficacy, as well as the relationship between HSP90AB1 single-nucleotide polymorphisms (SNPs) and GCs efficacy. HSP90AB1 CNVs and SLE risk were analysed in 519 patients and 538 controls. Patients treated with GCs were followed up for 12 weeks and were divided into sensitive and insensitive groups to investigate the effects of CNVs (419 patients) and SNPs (457 patients) on the efficacy of GCs. Health-related quality of life (HRQoL) was also measured by SF-36 at baseline and week 12 to explore the relationship between CNVs/SNPs and HRQoL improvements in Chinese SLE patients. Our results indicated a statistically significant association between HSP90AB1 CNVs and SLE (PBH  = 0.039), and this association was more pronounced in the female subgroup (PBH  = 0.039). However, we did not detect association of HSP90AB1 CNVs/SNPs with efficacy of GCs. But we found a marginal association between SNP rs13296 and improvement in Role-emotional, while this association was not strong enough to survive in the multiple testing corrections. Collectively, our findings suggest that the copy number of HSP90AB1 is associated with SLE susceptibility. But copy number and polymorphisms of HSP90AB1 may not be associated with efficacy of GCs.

Correlation between systemic osteoporosis and local bone erosion with rheumatoid arthritis patients in Chinese population.

OBJECTIVE: RA is a systemic auto-immune inflammatory disease that can lead to local bone erosions and generalized osteoporosis (OP). The aim of this study was to investigate the relationship between systemic osteoporosis and local bone erosion with RA patients in the Chinese population. METHODS: In total, 1235 patients with RA and 158 normal subjects were enrolled in this study. Clinical and laboratory features were recorded in detail. Information about functional class and physical activity was collected using specific questionnaires. Dual-energy X-ray absorptiometry was used to measure BMD. The MECALL castor-50-hf model X-ray scanner was used for two-hand (including wrist) photographs. RESULTS: The median Sharp scores differed significantly between the normal bone mass group, osteopenia group and OP group (P < 0.001). There was a modest negative linear correlation between Sharp and HAQ scores and longer disease duration (P < 0.001). There was a clear increasing trend in Sharp score, incidence of OP and HAQ score in the different DAS in 28 joints (DAS28) activity groups (P < 0.001). Spearman's correlation test showed that Sharp and HAQ scores were negatively correlated with BMD at all measured sites (femoral neck, total hip and L1-4) (P < 0.001). Logistic regression indicated that age, female gender, and Sharp and HAQ scores were independent risk factors in the occurrence of OP in RA patients. The use of DMARDs and BMI were protective factors for OP. CONCLUSION: These results suggest that BMD is associated with local bone erosion among Chinese patients with RA. Local bone erosion is closely related to clinical symptoms and BMD in patients with RA.

Chronic obstructive pulmonary disease in rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: The risk and prevalence of chronic obstructive pulmonary disease (COPD) in rheumatoid arthritis (RA) is still obscure. The current study was aimed to systematically review and meta-analyse the risk ratio (RR) and prevalence of COPD in RA. METHODS: A comprehensive systematic review was conducted based on PubMed, Web of Science and Cochrane Library from inception to April 30, 2018. The primary outcome of our study was the RR of COPD in RA patients compared with controls, and secondary was the prevalence of COPD in RA patients. Pooled effect sizes were calculated according to fixed effect model or random effects model depending on heterogeneity. RESULTS: Six and eight studies reported the RR and prevalence of COPD in RA respectively. Compared with controls, RA patients have significant increased risk of incident COPD with pooled RR 1.82 (95% CI = 1.55 to 2.10, P <  0.001). The pooled prevalence of COPD in RA patients was 6.2% (95% CI = 4.1 to 8.3%). Meta-regression identified that publication year was an independent covariate negatively associated with the RR of COPD, and smoker proportion of RA population was also positively associated with the prevalence of COPD significantly in RA patients. CONCLUSIONS: The present meta-analysis has demonstrated the significant increased risk and high prevalence of COPD in RA patients. Patients with RA had better cease tobacco use and rheumatologists should pay attention to the monitoring of COPD for the prevention and control of COPD.