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International Journal Of Rheumatic Diseases[JOURNAL]

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Metformin Suppress Th17 Differentiation and Function to Improve Glandular Function in Primary Sjögren's Syndrome.

Wang J, Liu M, Fan Z … +5 more , Li Z, Wang L, Wang L, Mei Y, Liu Z

Int J Rheum Dis · 2026 May · PMID 42080568 · Publisher ↗

PURPOSE: This study aims to investigate the effects of metformin on T cell differentiation and the underlying mechanisms in NOD/Ltj mice, a model for primary Sjögren's syndrome (pSS). Specifically, we focus on metformin'... PURPOSE: This study aims to investigate the effects of metformin on T cell differentiation and the underlying mechanisms in NOD/Ltj mice, a model for primary Sjögren's syndrome (pSS). Specifically, we focus on metformin's role in modulating Th17 differentiation and its potential regulation through the mTOR/STAT3 signaling pathway. METHODS: We established a metformin-treated pSS mouse model. Salivary flow rate, histological analysis, and flow cytometry were employed to assess inflammation and T cell subsets. Cytokine secretion was measured using qPCR, ELISA, and Western blot analysis. To investigate the molecular pathways involved, we examined mTOR/STAT3 signaling and administered mTOR and STAT3 agonists. RESULTS: Metformin treatment significantly alleviated salivary gland inflammation and increased salivary flow in pSS mice. Flow cytometry showed that metformin reduced the proportions of Th1, Th2, and Th17 cells, while increasing Treg cells. The reduction in Th17 cells was the most prominent. Furthermore, metformin decreased the levels of pro-inflammatory cytokines (IL-21, IL-22, IFN-γ) and increased anti-inflammatory cytokines (IL-4, IL-10). Immunohistochemistry and Western blot analysis demonstrated that metformin inhibited IL-17 expression. Additionally, metformin treatment suppressed the mTOR/STAT3 signaling pathway, and mTOR/STAT3 agonists reversed the effects of metformin on Th17 differentiation. CONCLUSION: Metformin effectively modulates T cell differentiation and alleviates pSS symptoms, primarily by suppressing Th17 cell differentiation through the mTOR/STAT3 pathway. These findings provide insights into the therapeutic mechanisms of metformin in pSS and suggest its potential as a treatment strategy for immune-mediated diseases.
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Navigating the Biomarker Landscape in Still's Disease and Macrophage Activation Syndrome: Toward Precision Diagnosis and Management.

Lai IC, Wu CC, Liao PF

Int J Rheum Dis · 2026 May · PMID 42080557 · Publisher ↗

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Confronting the Gout Crisis in the Pacific: A Neglected Public Health and Cultural Challenge.

Lorenzo JP, Wei JC

Int J Rheum Dis · 2026 May · PMID 42080549 · Publisher ↗

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Case Report: Acute Exacerbation of Rheumatoid Arthritis-Associated Interstitial Lung Disease Preceded by Cutaneous Vasculitis: Implications for a Shared Pathogenesis.

Suzuki K, Akiyama M, Kaneko Y

Int J Rheum Dis · 2026 May · PMID 42080528 · Publisher ↗

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Big Data Research: A Bridge From Basic Research to Clinical Trial Emulation.

Chang R, Hung YM, Wei JC

Int J Rheum Dis · 2026 May · PMID 42059784 · Publisher ↗

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Deciphering 5th-Digit Sesamoiditis During Hand Ultrasound Examination.

Yalçınkaya B, Abacıoğlu HB, Çolak AF … +2 more , Yıldız AE, Özçakar L

Int J Rheum Dis · 2026 May · PMID 42059779 · Publisher ↗

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Case Report: A Case of Refractory Polyarteritis Nodosa Treated With High-Dose Tofacitinib.

Pereira da Costa R, Lopes AR, de Vasconcelos P … +2 more , Duarte S, Khmelinskii N

Int J Rheum Dis · 2026 May · PMID 42059333 · Publisher ↗

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Aseptic Abscess Syndrome Associated With Relapsing Polychondritis-A Rarely Reported Association.

Pridhivi B, Soneja M, Kumar R … +2 more , Wig N, Jain S

Int J Rheum Dis · 2026 May · PMID 42053214 · Publisher ↗

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Labyrinth of Rheumatic Disease: Finding the Optimal Path to Managing Cardiovascular Risk.

Wu J, Guo Q, Yin C … +2 more , Wei JC, Zhang LY

Int J Rheum Dis · 2026 May · PMID 42053182 · Publisher ↗

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Drug-Induced Subacute Cutaneous Lupus Erythematosus Under Adalimumab in a Child With Polyarticular Juvenile Idiopathic Arthritis: IFN-α and TNF-α-Skewed Cytokine Profile.

Aida Y, Mizuta M, Hatano M … +2 more , Shimizu M, Nakagishi Y

Int J Rheum Dis · 2026 May · PMID 42033659 · Publisher ↗

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Case Report: Atypical Presentation of Nivolumab-Induced Immune-Related Vasculopathy Imitating Raynaud's Phenomenon in Lung Cancer.

Temi YB, Yazıcı A

Int J Rheum Dis · 2026 May · PMID 42028910 · Publisher ↗

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HPV Vaccination in Rheumatology: An Overlooked Opportunity for Infection Prevention and Beyond.

Liu YY, Chen HY, Tu YH … +2 more , Yong SB, Yii CY

Int J Rheum Dis · 2026 May · PMID 42028894 · Publisher ↗

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CAR-T Therapies and Emerging Alternatives: Reassessing Cost-Effectiveness and Future Directions in Modern Immunotherapy.

Wang YC, Li CJ, Yong SB … +1 more , Shih PC

Int J Rheum Dis · 2026 May · PMID 42028893 · Publisher ↗

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The Application, Advantages, and Limitations of Mendelian Randomization Analysis in Ankylosing Spondylitis.

Wu M, Wang M, Wu X … +2 more , Yu Y, Mao Y

Int J Rheum Dis · 2026 May · PMID 42027182 · Publisher ↗

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Hyperuricemia Among College Students: Dietary Prevention May Be an Effective Measure.

Ma W, Xu M, Sun Z … +2 more , Gu R, Wang X

Int J Rheum Dis · 2026 May · PMID 42027181 · Publisher ↗

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Adjunctive Dapsone Therapy in Pediatric Systemic Lupus Erythematosus With Cutaneous and Vasculitic Overlap: Implications for Stable Lupus Nephritis.

Chen HJ, Yong SB, Wang SH … +2 more , Liu XL, Wu CY

Int J Rheum Dis · 2026 Apr · PMID 42012323 · Publisher ↗

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Case Report: IgG4-Related Disease With Isolated Spinal Involvement.

Wang F, Guo Z, Wang X … +2 more , Xia X, Jin H

Int J Rheum Dis · 2026 Apr · PMID 42012322 · Publisher ↗

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Breakthrough Biologics: Charting the Course for Sjögren's Syndrome Treatment in 2024.

Hsu TC, Wei JC

Int J Rheum Dis · 2026 Apr · PMID 42012307 · Publisher ↗

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A Unified, Stratified Approach to the Large Vessel Vasculitis Spectrum and Imaging Implications.

Harigai M, Kong KO, Dasgupta B

Int J Rheum Dis · 2026 Apr · PMID 42012306 · Publisher ↗

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Real-World Data of Tofacitinib Versus Tumor Necrosis Factor Inhibitors in Taiwanese Patients With Rheumatoid Arthritis From a Drug-Based Cohort Study.

Hsieh SC, Chen WS, Hu JC … +7 more , Sung WY, Tsai WC, Chen HC, Huang CM, Kuo E, Gruben D, Chen YH

Int J Rheum Dis · 2026 Apr · PMID 42012300 · Publisher ↗

AIM: To assess the long-term effectiveness and safety of, and persistence/adherence to, tofacitinib (an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis [RA]) and tumor necrosis factor inhibitors (TN... AIM: To assess the long-term effectiveness and safety of, and persistence/adherence to, tofacitinib (an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis [RA]) and tumor necrosis factor inhibitors (TNFi) in Taiwanese patients with RA in real-world settings. METHODS: This was a 5 year, prospective cohort study in Taiwanese patients with RA newly initiating tofacitinib or TNFi. Patients received standard care per treating rheumatologists and fulfillment of National Health Insurance reimbursement criteria. Effectiveness outcomes (baseline and every 24 weeks) included: Disease Activity Score in 28 joints, erythrocyte sedimentation rate; Clinical Disease Activity Index; Health Assessment Questionnaire-Disability Index; and Work Productivity and Activity Impairment-RA. Differences between groups were compared using mixed logistic regression models. Safety and persistence/adherence were assessed throughout. RESULTS: In total, 267 patients were included (tofacitinib, n = 145; TNFi, n = 122). No significant differences in effectiveness outcomes for tofacitinib versus TNFi were reported before or after propensity score adjustment. In patients receiving tofacitinib and TNFi, rates of adverse events (AEs; 56.6% vs. 55.7%), serious AEs (20.0% vs. 21.3%), major adverse cardiovascular events (0% vs. 0.8%), malignancy (2.1% vs. 0.8%), and deaths (1.4% vs. 3.3%) were similar. Serious infections/herpes zoster occurred in 13.1%/12.4% and 8.2%/3.3% of patients receiving tofacitinib and TNFi, respectively. No venous thromboembolism events were reported. Persistence/adherence was comparable between tofacitinib and TNFi. CONCLUSION: Tofacitinib effectiveness and persistence/adherence were generally similar to TNFi in this real-world analysis in Taiwanese patients with RA. Safety outcomes were consistent with the known safety profiles of tofacitinib and TNFi. TRAIL REGISTRATION: EUPAS13431.
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