{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:09:41Z","timestamp":1793207381561,"version":"4.5.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a complex immune-mediated inflammatory disease involving multiple dysregulated signaling pathways and marked inter-individual heterogeneity in treatment response. In real-world clinical practice in China, traditional Chinese medicine (TCM) is widely used for RA management in the form of multi-herbal prescriptions; however, systematic approaches that link heterogeneous TCM prescription patterns to objective clinical signals and underlying molecular mechanisms remain limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, large-scale inpatient electronic medical records from two tertiary hospitals were analyzed to identify representative TCM prescriptions used for RA treatment. Frequent closed itemset mining combined with compression strategies was applied to extract stable and non-redundant core prescription patterns across different physicians. Retrospective clinical validation was conducted using longitudinal changes in C-reactive protein (CRP) as an objective biomarker of inflammatory activity. Systems pharmacology approaches\u2014including network pharmacology, network topology-based proximity analysis, and molecular docking\u2014were integrated to characterize shared and prescription-specific molecular targets, signaling pathways, and compound-target interaction feasibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Five representative core TCM prescriptions were identified. Among 614 eligible patients receiving these prescriptions, all groups exhibited significant post-treatment reductions in CRP levels (p &amp;lt; 0.05), indicating consistent anti-inflammatory signals in real-world settings. Network pharmacology analysis revealed substantial overlap between prescription targets and RA-associated genes (65\u2013115 targets per prescription), with convergent enrichment in key inflammatory pathways, including Toll-like receptor, IL-17, and TNF signaling pathway. Network proximity metrics demonstrated close associations between prescription targets and the RA disease module. Molecular docking further supported the structural plausibility of direct interactions between representative active compounds\u2014such as quercetin and berberine\u2014and core RA-related targets, including TNF-\u03b1 and PTGS2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This integrative analysis demonstrates that heterogeneous TCM prescriptions used in RA converge on shared inflammatory regulatory networks while retaining prescription-specific mechanistic features. By linking real-world clinical evidence with systems-level and structural analyses, this study provides a reproducible framework for mechanistic interpretation of TCM-based therapeutic heterogeneity and generates testable hypotheses for future prospective and stratified RA studies incorporating standardized clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1792988","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:35:08Z","timestamp":1774254908000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Mining personalized core traditional Chinese medicine prescriptions for rheumatoid arthritis and elucidating their mechanisms via frequent closed Itemset compression and multilevel network pharmacology"],"prefix":"10.3389","volume":"13","author":[{"given":"Xu","family":"Chen","sequence":"first","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Yu","sequence":"additional","affiliation":[{"name":"National Data Center of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Dong","sequence":"additional","affiliation":[{"name":"Beijing Jiaotong University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangfan","family":"Chen","sequence":"additional","affiliation":[{"name":"National Data Center of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangshan","family":"Tian","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"Wangjing Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Guo","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Jiaotong University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Fa","sequence":"additional","affiliation":[{"name":"National Data Center of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiu","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]},{"name":"National Data Center of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"B1","first-page":"487","article-title":"Fast algorithms for mining association rules in large databases","volume-title":"Proceedings of the 20th international conference on Very Large Data Bases (VLDB)","author":"Agrawal","year":"1994"},{"key":"B2","doi-asserted-by":"publisher","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The Gene Ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1196\/annals.1423.034","article-title":"Autoantibody production in anti-TNF-alpha-treated patients","volume":"1110","author":"Alessandri","year":"2007","journal-title":"Ann. 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