Publication Name	World Journal of Orthopedics
Manuscript ID	125433
Country	China

Category	Rheumatology
Manuscript Type	Basic Study
Article Title	Integrating Mendelian randomization and enzyme-linked immunosorbent assay validation identifies candidate mediators across the rheumatoid arthritis disease continuum
Manuscript Source	Unsolicited Manuscript
All Author List	Yuan-Song Song, Jun-Ling Luo, Xi-Fan Zheng, Ye-Ping Chen, Ze-Ming Li and Jun Yao
Funding Agency and Grant Number	Funding Agency Grant Number Guangxi Traditional Chinese Medicine Appropriate Technology Development and Promotion Project No. GZSY22-62 Guangxi Natural Science Foundation No. 2023GXNSFAA026402 First Affiliated Hospital of Guangxi Medical University Innovation Team Cultivation Program No. YYZS2023004
Corresponding Author	Jun Yao, Chief Physician, MD, Professor, Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. yaojun800524@126.com
Key Words	Rheumatoid arthritis; Mendelian randomization; Inflammatory cytokines; CD40; C-C motif chemokine ligand 28; Matrix metalloproteinase-1; Interleukin-18 receptor 1; Enzyme-linked immunosorbent assay
Core Tip	This study integrates Mendelian randomization with enzyme-linked immunosorbent assay validation to identify CD40, C-C motif chemokine ligand 28, and matrix metalloproteinase-1 as candidate mediators in rheumatoid arthritis, while interleukin-18 receptor 1 shows discordant Mendelian randomization (protective) and enzyme-linked immunosorbent assay (elevated) findings requiring mechanistic reconciliation. A hypothesised spatiotemporal cascade links CD40 to lymphoid immunity, C-C motif chemokine ligand 28 to synovitis, and matrix metalloproteinase-1 to cartilage degradation. Their positive intercorrelations suggest a potential synergistic loop, supporting further exploration of composite biomarker panels and combination strategies. Experimental validation demonstrates protein-level consistency rather than proof of causality, and all findings should be considered hypothesisgenerating.
Citation	Song YS, Luo JL, Zheng XF, Chen YP, Li ZM, Yao J. Integrating Mendelian randomization and enzyme-linked immunosorbent assay validation identifies candidate mediators across the rheumatoid arthritis disease continuum. World J Orthop 2026; In press

Received	2026-07-07 07:08
Peer-Review Started	2026-07-07 07:08
First Decision by Editorial Office Director
Return for Revision	2026-08-06 01:31
Revised	2026-08-16 06:01
Publication Fee Transferred	2026-08-26 04:22
Second Decision by Editor	2026-10-08 07:40
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-10-08 09:14
Articles in Press	2026-10-08 09:14
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	2218-5836 (online)
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