Inflammatory bowel disease activity threatens ankylosing spondylitis: implications from Mendelian randomization combined with transcriptome analysis.

Background: Inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) share common traits of chronic recurrent inflammation affecting both the intestines and joints. Epidemiological studies have revealed that the incidence of AS has jumped from 0.3% to 3% among patients with IBD. However, these findings do not definitively establish a causal relationship whereby IBD directly leads to the development of AS. Moreover, whether the activity of IBD will have an impact on this process remains a pending question. Methods: Two-sample Mendelian randomization (MR) analyses were employed across multiple datasets to investigate the potential of IBD as a risk factor for AS. The pathogenic genes of AS were identified by MR analysis of expression quantitative trait locus. Risk scores for active and inactive patients were calculated by single-sample gene set enrichment analysis. Comparative assessments encompassing alterations in risk transcription factor activity, shifts in signaling pathways, and variances in immune cell profiles were conducted between active and inactive patients. Moreover, the correlation of immune cells and risk genes was quantified. Results: A total of 6 MR analyses, conducted across 3 exposure datasets and 2 outcome datasets, consistently revealed that IBD substantially elevates the risk of AS development. The MR analysis of the two outcome datasets identified 66 and 54 risk genes, respectively. Notably, both the risk scores computed from the two distinct sets of risk genes were notably higher in active patients compared to their inactive counterparts. Discernible variations in the activity of risk-associated transcription factors were observed between active and inactive patients. In addition, three inflammatory pathways exhibited marked activation in active patients. Moreover, seven specific immune cell types, closely linked to disease activity, exhibited statistically significant correlations with the identified risk genes. Conclusion: By combining Mendelian randomization with transcriptome analysis, this study postulates IBD as a significant risk factor for AS, and further presents innovative evidence for the impact of IBD activity on the progression of AS.

Concerned About the Shortage of Paediatricians in Developing Countries.

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Immune cells and their related genes provide a new perspective on the common pathogenesis of ankylosing spondylitis and inflammatory bowel diseases.

Background: The close relationship between ankylosing spondylitis (AS) and inflammatory bowel diseases (IBD) has been supported by many aspects, including but not limited to clinical manifestations, epidemiology and pathogenesis. Some evidence suggests that immune cells actively participated in the pathogenesis of both diseases. However, information on which cells are primarily involved in this process and how these cells mobilize, migrate and interact is still limited. Methods: Datasets were downloaded from Gene Expression Omnibus (GEO) database. Common differentially expressed genes (coDEGs) were identified by package "limma". The protein-protein interaction (PPI) network and Weighted Gene Co-Expression Network Analysis (WGCNA) were used to analyze the interactions between coDEGs. KEGG pathway enrichment analysis and inverse cumulative distribution function were applied to identify common differential pathways, while Gene Set Enrichment Analysis (GSEA) was used to confirm the significance. Correlation analysis between coDEGs and immune cells led to the identification of critical immune-cell-related coDEGs. The diagnostic models were established based on least absolute shrinkage and selection operator (LASSO) regression, while receiver operating characteristic (ROC) analysis was used to identify the ability of the model. Validation datasets were imported to demonstrate the significant association of coDEGs with specific immune cells and the capabilities of the diagnostic model. Results: In total, 67 genes were up-regulated and 185 genes were down-regulated in both diseases. Four down-regulated pathways and four up-regulated pathways were considered important. Up-regulated coDEGs were firmly associated with neutrophils, while down-regulated genes were significantly associated with CD8+ T-cells and CD4+ T-cells in both AS and IBD datasets. Five up-regulated and six down-regulated key immue-cell-related coDEGs were identified. Diagnostic models based on key immue-cell-related coDEGs were established and tested. Validation datasets confirmed the significance of the correlation between coDEGs and specific immune cells. Conclusion: This study provides fresh insights into the co-pathogenesis of AS and IBD. It is proposed that neutrophils and T cells may be actively involved in this process, however, in opposite ways. The immue-cell-related coDEGs, revealed in this study, may be relevant to their regulation, although relevant research is still lacking.

The combination of Chinese and Western Medicine in the management of rheumatoid arthritis: A real-world cohort study across China.

Objective: To investigate the efficacy of Integrative medicine (IM), compare with Western medicine (WM), in the treatment of rheumatoid arthritis (RA) in a cohort study. Methods: This is a cohort study with recruitment of RA patients from 10 hospitals in China. The primary outcome was change in disease activity score 28 (DAS28) during 4 follow-up visits. Generalized estimating equation (GEE) models that controlled for variables were used to investigate a time trend and assess group differences in the primary outcome and secondary outcomes after propensity score matching (PSM). Results: A total of 3195 patients with RA received IM (n = 1379, 43.2%) or WM (n = 1816, 56.8%). Following 1:1 propensity score matching, 1,331 eligible patients prescribed IM were compared to 1,331 matched patients prescribed WM. The GEE analysis with PSM showed that the IM was more beneficial to significantly decrease the levels of VAS, PGA and PhGA (VAS: odds ratio (OR), 0.76; 95% CI, 0.63-0.92; p = 0.004; PGA: OR, 0.76; 95% CI, 0.64-0.92; p = 0.007; and PhGA: OR, 0.77; 95% CI, 0.64, 0.93; p = 0.004), and reduce DAS28 (OR, 0.84; 95% CI, 0.73-0.98; p = 0.030) in the per-protocol population. Conclusion: This study suggests that compare to WM, IM has advantages in improving RA-related outcomes. However, the statistical significance might not reveal significant clinical difference. Further studies should be focused on specific treatment strategies and/or disease stages.

HLA-B27 negative reactive arthritis versus HLA-B27 positive reactive arthritis: A retrospective study.

Reactive arthritis (ReA) is defined as inflammatory arthritis secondary to an extra-articular infection with a key genetic background, HLA-B27. However, to date, the diagnosis and classification remain incomplete. The study focused on the similarities and differences in clinical manifestation, imaging features, and laboratory inspection between HLA-B27 negative patients and HLA-B27 positive patients in order to provide a reference for future development of diagnostic and classification criteria. Twenty-five ReA (19 HLA-B27 negative patients and 6 HLA-B27 positive patients) were included in this retrospective study. Clinical data, including demographics, clinical symptoms, imaging features, and laboratory inspection, were collected. The chi-square test and Mann-Whitney U test were used in the analysis. HLA-B27 negative group showed more involvement of upper extremities and small joints, while HLA-B27 positive group performed more axial symptoms. No significant difference was found in imaging features (ultrasound and magnetic resonance imaging) or laboratory inspection (microbes culture and infection-related indicators) between the 2 groups. ReA patients with different genetic backgrounds show various manifestations, although they encounter similar infections.

The potential value of fibrinogen to albumin ratio (FAR) in the assessment of inflammation in spondyloarthritis.

BACKGROUND: Fibrinogen to albumin ratio (FAR) is a newly investigated indicator for inflammation. The study aimed to explore the potential ability of FAR in assessing the severity of inflammation in spondyloarthritis. METHODS: The clinical data of 196 spondyloarthritis (SpA) patients, 66 osteoarthritis (OA) patients, and 81 healthy controls (HC) were collected in this retrospective study. The SpA group included 69 psoriatic arthritis patients, 47 reactive arthritis patients and 80 ankylosing spondylitis patients. Chi-square test and Mann-Whitney U test, Spearman's correlation test, regression analysis, and ROC analyses were used for the analysis of FAR. RESULTS: FAR level in group SpA was higher than in OA or HC. In the SpA group, the reactive arthritis group was characterized by the highest FAR level. After matching the erythrocyte sedimentation rate, a significant difference occurred between groups SpA and OA, but not in SpA subgroups. The FAR level was significantly related to erythrocyte sedimentation rate and C-reactive protein. After regression and receiver operating characteristics analysis, FAR was considered the most potential pointer to evaluate inflammation in SpA with the area under curve of 0.95. The recommended cut-off value of FAR was 9.44 for serious inflammation and 8.34 for mild conditions. CONCLUSION: FAR is closely related to inflammatory biomarkers and can be a potential indicator in the assessment of inflammation in spondyloarthritis.

Triptolide decreases rheumatoid arthritis fibroblast-like synoviocyte proliferation, invasion, inflammation and presents a therapeutic effect in collagen-induced arthritis rats via inactivating lncRNA RP11-83J16.1 mediated URI1 and ß-catenin signaling.

OBJECTIVE: Our previous study observed that long non-coding RNA (lncRNA) RP11-83J16.1 promoted rheumatoid arthritis (RA)-fibroblast-like synoviocyte (RA-FLS) proliferation, invasion and inflammation, which was downregulated by triptolide treatment. Therefore, the present study aimed to further investigate the mechanism and interaction between triptolide and lncRNA RP11-83J16.1 in RA treatment in vitro and in vivo. METHODS: RA-FLS was isolated and treated by different concentration of triptolide and lncRNA RP11-83J16.1 overexpression plasmid. Furthermore, collagen-induced arthritis (CIA) rat model was constructed followed by triptolide and lncRNA RP11-83J16.1 overexpression plasmid treatment. RESULTS: Triptolide inhibited RA-FLS viability and lncRNA RP11-83J16.1 expression in a dose-dependent manner. Afterward, triptolide treatment inhibited RA-FLS proliferation, invasion, levels of inflammatory markers (TNF-α, IL-1ß, IL-6, MMP-3, and MMP-9), inactivated lncRNA RP11-83J16.1, URI1 and ß-catenin signaling, but promoted apoptosis. However, lncRNA RP11-83J16.1 overexpression weakened the effects of triptolide on regulating RA-FLS cell behaviors, URI1 signaling and ß-catenin signaling. In CIA model, triptolide decreased arthritis score, hyperproliferation of synovial cells, inflammation infiltration of synovial tissue, inflammatory markers (TNF-α, IL-1ß, IL-6, MMP-3, and MMP-9), inactivated lncRNA RP11-83J16.1, URI1 and ß-catenin signaling, but increased cell apoptosis rate of synovial tissue. Nevertheless, lncRNA RP11-83J16.1 curtailed the treatment effect of triptolide in CIA model. CONCLUSION: Triptolide decreases RA-FLS proliferation, invasion, inflammation and presents a therapeutic effect in CIA model via inactivating lncRNA RP11-83J16.1 mediated URI1 and ß-catenin signaling.

Epidemiology of Takayasu arteritis in Shanghai: A hospital-based study and systematic review.

BACKGROUND: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. METHODS: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. RESULTS: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. CONCLUSIONS: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

The Anti-Inflammatory and Uric Acid Lowering Effects of Si-Miao-San on Gout.

Background: Si-Miao-San (SMS) is a well-known traditional Chinese medicine. This study aims to evaluate the anti-inflammatory effects of SMS on gouty arthritis and its potential mechanism of action. Methods: The effects and mechanism of SMS were evaluated in monosodium urate (MSU)-treated mice or macrophages. The expression of cytokines and PI3K/Akt was analyzed using real-time PCR and Western blotting analyses. Macrophage polarization was assessed with immunofluorescence assays, real-time PCR, and Western blotting. Mass spectrometry was used to screen the active ingredients of SMS. Results: Pretreatment with SMS ameliorated MSU-induced acute gouty arthritis in mice with increased PI3K/Akt activation and M2 macrophage polarization in the joint tissues. In vitro, SMS treatment significantly inhibited MSU-triggered inflammatory response, increased p-Akt and Arg-1 expression in macrophages, and promoted M2 macrophage polarization. These effects of SMS were inhibited when PI3K/Akt activation was blocked by LY294002 in the macrophages. Moreover, SMS significantly reduced serum uric acid levels in the hyperuricemia mice. Using mass spectrometry, the plant hormones ecdysone and estrone were detected as the potentially effective ingredients of SMS. Conclusion: SMS ameliorated MSU-induced gouty arthritis and inhibited hyperuricemia. The anti-inflammatory mechanism of SMS may exert anti-inflammatory effects by promoting M2 polarization via PI3K/Akt signaling. Ecdysone and estrone might be the potentially effective ingredients of SMS. This research may provide evidence for the application of SMS in the treatment of gout.

Rapid remission of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome in response to the Janus kinase inhibitor tofacitinib: A case report.

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disease for which clinical treatment has not been standardized. Janus kinase (JAK) inhibitors represent a novel therapeutic option for rheumatoid arthritis, psoriatic arthritis, and some other autoinflammatory diseases. However, the clinical utility of JAK inhibitors in treating SAPHO syndrome has not been thoroughly investigated. In this study, we describe a patient with SAPHO syndrome who failed to respond to conventional treatment but demonstrated a remarkable and rapid response to the JAK inhibitor tofacitinib. CASE SUMMARY: A 62-year-old female patient presented with swelling and pain at the sternoclavicular joints, back pain that limited her activities, arthralgia in the right knee, and cutaneous lesions. Her symptoms were unresponsive to nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, Tripterygium wilfordii hook f, and bisphosphonates. SAPHO syndrome was diagnosed in accordance with dermatological and osteoarticular manifestations and abnormal inflammatory factors. Multiple image studies have illustrated bone lesions and pathological fractures of vertebral bodies. Oral treatment with tofacitinib at 5 mg twice daily with methotrexate and bisphosphonates was initiated. The patient reported that her pain symptoms were relieved after 3 d and her cutaneous lesions were reduced after 4 wk of treatment. Vertebral lesions were improved after 6 mo on tofacitinib. No serious adverse effects were noted. CONCLUSION: JAK inhibitor therapy may be a promising strategy to treat SAPHO syndrome.

The Diagnostic Value of Antibodies Against Citrullinated or Carbamylated Fibrinogen in Rheumatoid Arthritis.

BACKGROUND: This study aimed to evaluate the overall diagnostic value of citrullinated or carbamylated fibrinogen antibodies in patients with rheumatoid arthritis (RA). METHODS: Serum samples collected from 114 patients with established RA, 143 patients with non-RA diseases, and 200 healthy controls were tested by ELISA for citrullinated fibrinogen (Cit-fib), carbamylated fibrinogen (Ca-fib), and chimeric fibrinogen a/b chain citrullinated peptides (CFABCP). Diagnostic indexes and correlations with titers were calculated, cross reactivities of Cit-fib, Ca-fib, and CFABCP were assessed by competition experiments. RESULTS: With a cutoff ensuring 98% specificity for RA patients versus healthy controls, the sensitivities of Cit-fib and Ca-fib are 66.67% and 24.6%, respectively, while the sensitivity of CFABCP was 74.56%. Cit-fib, Ca-fib, and CFABCP can inhibit reciprocally in competition experiments. As for non-RA patients, the positive rate of Ca-fib was higher than that of Cit-fib and CFABCP. CONCLUSIONS: Citrullination and carbamylation of fibrinogen both have a role in RA diagnosing, but citrullination is better. The recombination of peptides, CFABCP, has high specificity and considerable sensitivity for diagnosis for RA patients.

Challenges in Treatment of Primary Sjögren's Syndrome and Opportunities for Chinese Medicine.

Primary Sjögren's syndrome is a chronic autoimmune disease that can lead to systemic manifestations. At present, immunomodulatory agents have not shown good efficacy, many patients in China seek Chinese medicine treatment. Chinese medicine can comprehensively improve the symptoms of patients through Chinese pattern diagnosis and individualized treatment. Fundamental researches are providing scientific bases for the therapeutic effect of Chinese medicine. Professional Chinese medicine treatment can be integrated into the conventional management of primary Sjögren's syndrome.

Effectiveness of Traditional Chinese Medicine Compound JieDuTongLuoShengJin Granules Treatment in Primary Sjögren's Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the clinical therapeutic efficacy and safety of JieDuTongLuoShengJin granules + HCQ in patients with pSS. METHODS: 40 patients with low-activity-level pSS and without visceral involvement participated in this study and were randomized to receive either JieDuTongLuoShengJin granules with HCQ or placebo with HCQ. Patients and investigators were blinded to treatment allocation. The primary endpoint was week 12 ESSPRI score, while secondary endpoints included ESSDAI, salivary and lacrimal gland function, and some laboratory variables. Safety-related data were also assessed. RESULTS: Comparing with the placebo group, the treatment group experienced statistically significant improvement in the mean change from baseline for the primary endpoint of ESSPRI score and also in PGA. Moreover, in comparison with baseline values, the treatment group had significantly improved ESSDAI score, unstimulated saliva flow rate, and several laboratory variables. However, upon comparison of the two groups, there were no significant differences for them. The incidence of AEs was 10.0%, one in treatment group and three in placebo group. CONCLUSION: Treatment with a combination of JieDuTongLuoShengJin granules with HCQ is effective in improving patients' subjective symptoms and some objective indicators of pSS. These results indicate that JieDuTongLuoShengJin is promising as a safe and effective treatment of pSS.

Predicting the potential ankylosing spondylitis-related genes utilizing bioinformatics approaches.

Given that ankylosing spondylitis (AS) occurs in approximately 5 out of 1,000 adults of European descent and the unclear pathogenesis, the aim of the research was to further predict the molecular mechanism of this disease. The Affymetrix chip data GSE25101 were available from Gene Expression Omnibus database. First of all, differentially expressed genes (DEGs) were identified by Limma package in R. Moreover, DAVID was used to perform gene set enrichment analysis of DEGs. In addition, miRanda, miRDB, miRWalk, RNA22 and TargetScan were applied to predict microRNA-target associations. Meanwhile, STRING 9.0 was utilized to collect protein-protein interactions (PPIs) with confidence score >0.4. Then, the PPI networks for up- and down-regulated genes were constructed, and the clustering analysis was undergone using ClusterONE. Finally, protein-domain enrichment analysis of modules was conducted using DAVID. Total 145 DEGs were identified, including 103 up-regulated and 42 down-regulated genes. These DEGs were significantly enriched in phosphorylation (p = 1.21E-05) and positive regulation of gene expression (p = 1.25E-03). Furthermore, one module was screened out from the up-regulated network, which contained 39 nodes and 205 edges. Moreover, the nodes in the module were significantly enriched in ribosomal protein (RPL17, ribosomal protein L17 and MRPL22, mitochondrial ribosomal protein L22) and proteasome (PSMA6, proteasome subunit, alpha type 6, PSMA4)-related domains. Our findings that might explore the potential pathogenesis of AS and RPL17, MRPL22, PSMA6 and PSMA4 have the potential to be the biomarkers for the disease.

Temporal gene expression analysis of Sjögren's syndrome in C57BL/6.NOD-Aec1Aec2 mice based on microarray time-series data using an improved empirical Bayes approach.

The purpose of this study was to analyze the temporal gene expression in salivary and lacrimal glands of Sjögren's syndrome (SS) based on time-series microarray data. We downloaded gene expression data GSE15640 and GSE48139 from gene expression omnibus and identified differentially expressed genes (DEGs) at varying time points using a modified Bayes analysis. Gene clustering was applied to analyze the expression differences in time series of the DEGs. Protein-protein interaction networks were used for searching the hub genes, and gene ontology (GO) and KEGG pathways were applied to analyze the DEGs at a functional level. A total of 744 and 1,490 DEGs were screened out from the salivary glands and lacrimal glands, respectively. Among these genes, 194 were overlapped between salivary glands and lacrimal glands, and these genes were compartmentalized into six clusters with different expression profiles. The GO terms of intracellular transport, protein transport and protein localization were significantly enriched by DEGs in salivary glands; while in the lacrimal glands, DEGs were significantly enriched in protein localization, establishment of protein localization and protein transport. Our results suggest that the SS pathogenesis was significantly different in time series in the salivary and lacrimal glands. The DEGs whose expressions may correlate with molecular mechanisms of SS in our study might provide new insight into the underlying cause or regulation of this disease.

The risk factors for nosocomial infection in chinese patients with active rheumatoid arthritis in shanghai.

Objective. To analyse the potential risk factors of nosocomial infections in patients with active rheumatoid arthritis (RA). Methods. A total of 2452 active RA patients at Hospitals in Shanghai between January 2009 and February 2011 were analyzed. Their demographic and clinical characteristics were compared with those without infection, and the potential risk factors were determined by logistic regression analysis. Results. Multivariate analysis indicated the gender (OR = 0.70, 95% CI 0.53-0.92), duration in hospital (OR = 1.03 , 95%CI 1.01-1.05), number of organs involved (OR = 0.82, 95%CI 0.72-0.92), number of disease-modifying antirheumatic drugs ((DMARDs) (OR = 1.22, 95%CI 1.061-1.40)), corticosteroid therapy (OR = 1.02, 95%CI 1.01-1.03), peripheral white blood cell counts ((WBC) (OR = 1.04, 95%CI 1.00-1.08)), levels of serum albumin (OR = 0.98, 95%CI 0.97-0.99), and C-reactive protein ((CRP) (OR = 1.03 , 95%CI 1.01-1.04)) that were significantly associated with the risk of infections. Conclusion. The female patients, longer hospital stay, more organs involved, more DMARDs, corticosteroid usage, high counts of WBC, lower serum albumin, and higher serum CRP were independent risk factors of infections in active RA patients.