{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:39Z","timestamp":1787028579126,"version":"build-2736575974"},"reference-count":145,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heilongjiang University of Chinese Medicine Student","award":["KY2024-08"],"award-info":[{"award-number":["KY2024-08"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["30800303"],"award-info":[{"award-number":["30800303"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This review introduces and elaborates a novel temporal paradigm, the \u201cGout Inflammation Time Programming\u201d model, conceptualized through the Gout-STAT\u2122 framework. This model redefines gout inflammation as a dynamic continuum progressing through three precisely timed phases: an acute Perception phase (0\u201324 h) initiated by monosodium urate (MSU) crystal recognition, triggering the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and neutrophil-driven burst; a critical Adaptation phase (24\u201372 h) where outcomes are determined by immunometabolic reprogramming of macrophages and synovial fibroblasts; and a chronic Tissue Injury phase (&gt;72 h) driven by epigenetic memory, leading to irreversible osteoarticular destruction. Deciphering this programmed timeline reveals distinct therapeutic windows. We propose a shift towards stage-specific precision interventions, targeting upstream triggers (e.g., mitochondrial reactive oxygen species(ROS), neutrophil extracellular trap formation (NETosis)) in the acute phase, correcting metabolic checkpoints (e.g., succinate accumulation, impaired autophagy) during adaptation, and employing tissue-protective strategies (e.g., epigenetic modulators) in the chronic phase. Furthermore, we highlight the pivotal role of cutting-edge translational technologies, such as intelligent drug delivery systems and digital twin joint models, in achieving spatiotemporal precision. Understanding this intrinsic molecular clock is fundamental for advancing gout management from reactive treatment to a predictive, preventive, and personalized 4P medicine approach.<\/jats:p>","DOI":"10.3390\/ijms27031523","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T09:02:01Z","timestamp":1770195721000},"page":"1523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gout Inflammation Time Programming: Molecular Clock from Crystal Triggering to Tissue Remodeling"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8445-0120","authenticated-orcid":false,"given":"Xin","family":"Chen","sequence":"first","affiliation":[{"name":"First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanwen","family":"Zheng","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingping","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6426-4155","authenticated-orcid":false,"given":"Jieru","family":"Han","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrrheum.2017.155","article-title":"Inflammation in gout: Mechanisms and therapeutic targets","volume":"13","author":"So","year":"2017","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1136\/annrheumdis-2014-206258","article-title":"Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases","volume":"75","author":"Cleophas","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1007\/s10067-015-2933-y","article-title":"Molecular basis of oxidative stress in gouty arthropathy","volume":"34","author":"Pineda","year":"2015","journal-title":"Clin. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Moilanen, L.J., H\u00e4m\u00e4l\u00e4inen, M., Lehtim\u00e4ki, L., Nieminen, R.M., and Moilanen, E. (2015). Urate crystal induced inflammation and joint pain are reduced in transient receptor potential ankyrin 1 deficient mice\u2013potential role for transient receptor potential ankyrin 1 in gout. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117770"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature04516","article-title":"Gout-associated uric acid crystals activate the NALP3 inflammasome","volume":"440","author":"Martinon","year":"2006","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1002\/art.22938","article-title":"The role of interleukin-1 and the inflammasome in gout: Implications for therapy","volume":"56","author":"Pope","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.immuni.2021.05.004","article-title":"Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation","volume":"54","author":"Xian","year":"2021","journal-title":"Immunity"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13075-015-0522-8","article-title":"Epidemiology and management of gout in Taiwan: A nationwide population study","volume":"17","author":"Kuo","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s00109-015-1295-x","article-title":"How neutrophil extracellular traps orchestrate the local immune response in gout","volume":"93","author":"Hahn","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/eji.201545605","article-title":"PMA and crystal-induced neutrophil extracellular trap formation involves RIPK1-RIPK3-MLKL signaling","volume":"46","author":"Desai","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nm.3547","article-title":"Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines","volume":"20","author":"Schauer","year":"2014","journal-title":"Nat. Med."},{"key":"ref_12","first-page":"1793","article-title":"Does seasonality of the microbiota contribute to the seasonality of acute gout flare?","volume":"40","author":"Schlesinger","year":"2022","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6115","DOI":"10.1038\/ncomms7115","article-title":"Small heterodimer partner interacts with NLRP3 and negatively regulates activation of the NLRP3 inflammasome","volume":"6","author":"Yang","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s10067-015-2895-0","article-title":"Gadolinium-enhanced MRI features of acute gouty arthritis on top of chronic gouty involvement in different joints","volume":"34","author":"Emad","year":"2015","journal-title":"Clin. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/S0140-6736(16)00346-9","article-title":"Gout","volume":"388","author":"Dalbeth","year":"2016","journal-title":"Lancet"},{"key":"ref_16","first-page":"15","article-title":"Patients with gout can be cured in primary care","volume":"258","author":"Rees","year":"2014","journal-title":"Practitioner"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13075-015-0609-2","article-title":"An update on the genetic architecture of hyperuricemia and gout","volume":"17","author":"Merriman","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.taap.2018.06.022","article-title":"Flavonoids interfere with NLRP3 inflammasome activation","volume":"355","author":"Lim","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.4049\/jimmunol.1401611","article-title":"The cyclopentenone prostaglandin 15d-PGJ2 inhibits the NLRP1 and NLRP3 inflammasomes","volume":"194","author":"Maier","year":"2015","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1096\/fj.14-267393","article-title":"IL-1\u03b2 production is dependent on the activation of purinergic receptors and NLRP3 pathway in human macrophages","volume":"29","author":"Gicquel","year":"2015","journal-title":"FASEB J."},{"key":"ref_21","unstructured":"Coiffier, G., and Albert, J.D. (2015). Physiopathologie des arthropathies microcristallines Gout and and calcium pyrophosphate crystal arthropathies: Pathophysiology. Rev. Prat., 65, (In French)."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1136\/ard-2022-222764","article-title":"Type II collagen facilitates gouty arthritis by regulating MSU crystallisation and inflammatory cell recruitment","volume":"82","author":"Xu","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/ni.1631","article-title":"Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization","volume":"9","author":"Hornung","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/art.33355","article-title":"NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B(4) in a murine model of gout","volume":"64","author":"Amaral","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"106877","DOI":"10.1016\/j.intimp.2020.106877","article-title":"Role of T cells in the pathogenesis and treatment of gout","volume":"88","author":"Wang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13075-022-02742-9","article-title":"Treatment of gouty arthritis is associated with restoring the gut microbiota and promoting the production of short-chain fatty acids","volume":"24","author":"Park","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","article-title":"The single-cell transcriptional landscape of mammalian organogenesis","volume":"566","author":"Cao","year":"2019","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/1754-9485.12356","article-title":"Gouty arthropathy: Review of clinico-pathologic and imaging features","volume":"60","author":"Parathithasan","year":"2016","journal-title":"J. Med. Imaging Radiat. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13075-018-1714-9","article-title":"Monosodium urate burden assessed with dual-energy computed tomography predicts the risk of flares in gout: A 12-month observational study: MSU burden and risk of gout flare","volume":"20","author":"Pascart","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1084\/jem.20151570","article-title":"Immunometabolism governs dendritic cell and macrophage function","volume":"213","author":"Pearce","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1159\/000373960","article-title":"CARD8 rs2043211 polymorphism is associated with gout in a Chinese male population","volume":"35","author":"Chen","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rossaneis, A.C., Longhi-Balbinot, D.T., Bertozzi, M.M., Fattori, V., Segato-Vendrameto, C.Z., Badaro-Garcia, S., Zaninelli, T.H., Staurengo-Ferrari, L., Borghi, S.M., and Carvalho, T.T. (2019). Ru(bpy)2(NO)SO3(PF6), a Nitric Oxide Donating Ruthenium Complex, Reduces Gout Arthritis in Mice. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00229"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1186\/s12967-024-05261-0","article-title":"Fluorinated hydroxyapatite conditions a favorable osteo-immune microenvironment via triggering metabolic shift from glycolysis to oxidative phosphorylation","volume":"22","author":"Chen","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.cell.2016.08.064","article-title":"Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages","volume":"167","author":"Mills","year":"2016","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s00393-024-01587-8","article-title":"An observational study of ultrasound semiquantitative scoring for predicting the risk of gout flare","volume":"83","author":"Wang","year":"2024","journal-title":"Z. Rheumatol."},{"key":"ref_38","first-page":"1","article-title":"2016 ACR\/ARHP Annual Meeting Abstract Supplement","volume":"68","author":"Vestergaard","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1136\/gut.47.3.397","article-title":"Butyrate inhibits inflammatory responses through NFkappaB inhibition: Implications for Crohn\u2019s disease","volume":"47","author":"Segain","year":"2000","journal-title":"Gut"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.pharmthera.2005.04.013","article-title":"Adenosine 5\u2032-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation","volume":"112","author":"Bours","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Butera, G., Mullappilly, N., Masetto, F., Palmieri, M., Scupoli, M.T., Pacchiana, R., and Donadelli, M. (2019). Regulation of Autophagy by Nuclear GAPDH and Its Aggregates in Cancer and Neurodegenerative Disorders. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092062"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e30020","DOI":"10.1016\/j.heliyon.2024.e30020","article-title":"Identification of SOCS3 and PTGS2 as new biomarkers for the diagnosis of gout by cross-species comprehensive analysis","volume":"10","author":"Peng","year":"2024","journal-title":"Heliyon"},{"key":"ref_43","first-page":"812","article-title":"Acid-sensing ion channel 1a regulates the survival of nucleus pulposus cells in the acidic environment of degenerated intervertebral discs","volume":"19","author":"Cai","year":"2016","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.pop.2018.02.004","article-title":"Diagnosis and Treatment of Gout and Pseudogout for Everyday Practice","volume":"45","author":"Sidari","year":"2018","journal-title":"Prim. Care"},{"key":"ref_45","first-page":"795","article-title":"Delta neutrophil index contributes to the differential diagnosis between acute gout attack and cellulitis within 24 h after hospitalization","volume":"56","author":"Pyo","year":"2017","journal-title":"Rheumatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"725","DOI":"10.21037\/atm-22-15","article-title":"Endoplasmic reticulum stress triggered autophagy and regulated the phenotype transformation of rheumatoid arthritis synovial fibroblasts via the IRE1\/JNK pathway","volume":"10","author":"Wang","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: Renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological Functions of Autophagy Genes: A Disease Perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1001\/jama.2015.1881","article-title":"Nonsteroidal anti-inflammatory drugs for treatment of acute gout","volume":"313","author":"Wechalekar","year":"2015","journal-title":"JAMA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.semarthrit.2014.02.003","article-title":"Treatment of acute gout: A systematic review","volume":"44","author":"Khanna","year":"2014","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1097\/RHU.0000000000000235","article-title":"Does starting allopurinol prolong acute treated gout? A randomized clinical trial","volume":"21","author":"Hill","year":"2015","journal-title":"J. Clin. Rheumatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/BOR.0000000000000366","article-title":"Factors modulating the inflammatory response in acute gouty arthritis","volume":"29","author":"Cleophas","year":"2017","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1251086","DOI":"10.1126\/science.1251086","article-title":"Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity","volume":"345","author":"Saeed","year":"2014","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1093\/rheumatology\/kez196","article-title":"Gout and hyperuricaemia in the USA: Prevalence and trends","volume":"58","author":"Singh","year":"2019","journal-title":"Rheumatology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3454","DOI":"10.1021\/acs.jmedchem.7b01593","article-title":"Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors","volume":"61","author":"Sellmer","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s10020-023-00614-9","article-title":"Indole-3-propionic acid alleviates chondrocytes inflammation and osteoarthritis via the AhR\/NF-\u03baB axis","volume":"29","author":"Zhuang","year":"2023","journal-title":"Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nrrheum.2010.197","article-title":"The bone-cartilage unit in osteoarthritis","volume":"7","author":"Lories","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"20420188241227295","DOI":"10.1177\/20420188241227295","article-title":"Epidemiology of gout\u2014Global burden of disease research from 1990 to 2019 and future trend predictions","volume":"15","author":"Han","year":"2024","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105876","DOI":"10.1016\/j.jbspin.2025.105876","article-title":"Associations of the ALDH2 rs671 polymorphism and alcohol intake with early-onset gout in a Chinese male cohort","volume":"92","author":"Hu","year":"2025","journal-title":"Jt. Bone Spine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1093\/rheumatology\/key390","article-title":"Secular trends in the incidence and prevalence of gout in Denmark from 1995 to 2015: A nationwide register-based study","volume":"58","author":"Zobbe","year":"2019","journal-title":"Rheumatology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1038\/nature05836","article-title":"Gene-specific control of inflammation by TLR-induced chromatin modifications","volume":"447","author":"Foster","year":"2007","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cell.2012.12.018","article-title":"Latent enhancers activated by stimulation in differentiated cells","volume":"152","author":"Ostuni","year":"2013","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature11082","article-title":"Topological domains in mammalian genomes identified by analysis of chromatin interactions","volume":"485","author":"Dixon","year":"2012","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s10067-015-2991-1","article-title":"Efficacy and safety of etoricoxib compared with NSAIDs in acute gout: A systematic review and a meta-analysis","volume":"35","author":"Zhang","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s10067-020-05215-z","article-title":"The clinical efficacy of urate-lowering therapy in acute gout: A meta-analysis of randomized controlled trials","volume":"40","author":"Zhang","year":"2021","journal-title":"Clin. Rheumatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s13075-018-1606-z","article-title":"Gout and the risk of myocardial infarction in older adults: A study of Medicare recipients","volume":"20","author":"Singh","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1111\/imj.13969","article-title":"Acute arthritis: Predictive factors and current practice in the approach to diagnosis and management across two hospitals in Sydney","volume":"48","author":"Pavic","year":"2018","journal-title":"Intern. Med. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00774-020-01175-1","article-title":"Discovery of the RANKL\/RANK\/OPG system","volume":"39","author":"Yasuda","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09663","article-title":"A role for mitochondria in NLRP3 inflammasome activation","volume":"469","author":"Zhou","year":"2011","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kelley, N., Jeltema, D., Duan, Y., and He, Y. (2019). The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133328"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.1749-6632.2010.05627.x","article-title":"Animal and human studies with the mitochondria-targeted antioxidant MitoQ","volume":"1201","author":"Smith","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1016\/j.bbadis.2013.09.005","article-title":"MitoQ, a mitochondria-targeted antioxidant, delays disease progression and alleviates pathogenesis in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis","volume":"1832","author":"Mao","year":"2013","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Pang, M., Wang, S., Shi, T., and Chen, J. (2025). Overview of MitoQ on prevention and management of cardiometabolic diseases: A scoping review. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1506460"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.freeradbiomed.2024.12.027","article-title":"Nepetin limits NLRP3 inflammasome activation and alleviates NLRP3-driven inflammatory diseases via PINK1-dependent mitophagy","volume":"227","author":"Bu","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.immuni.2024.12.007","article-title":"Mitochondria and NLRP3: To die or inflame","volume":"58","author":"Yang","year":"2025","journal-title":"Immunity"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nchembio.1735","article-title":"Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation","volume":"11","author":"Lewis","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1084\/jem.20100239","article-title":"PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps","volume":"207","author":"Li","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1136\/annrheumdis-2011-200908","article-title":"Canakinumab for acute gouty arthritis in patients with limited treatment options: Results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions","volume":"71","author":"Schlesinger","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1161\/CIRCRESAHA.116.308445","article-title":"Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status","volume":"119","author":"Cameron","year":"2016","journal-title":"Circ. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/cr.2015.68","article-title":"Metabolic reprogramming in macrophages and dendritic cells in innate immunity","volume":"25","author":"Kelly","year":"2015","journal-title":"Cell Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nrc.2017.53","article-title":"Targeting autophagy in cancer","volume":"17","author":"Levy","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13075-019-1834-x","article-title":"Romidepsin suppresses monosodium urate crystal-induced cytokine production through upregulation of suppressor of cytokine signaling 1 expression","volume":"21","author":"Cleophas","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e20201416","DOI":"10.1084\/jem.20201416","article-title":"Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance","volume":"218","author":"He","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Martineau, X., Abed, \u00c9., Martel-Pelletier, J., Pelletier, J.P., and Lajeunesse, D. (2017). Alteration of Wnt5a expression and of the non-canonical Wnt\/PCP and Wnt\/PKC-Ca2+ pathways in human osteoarthritis osteoblasts. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180711"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12964-019-0411-x","article-title":"Wnt signaling: A promising target for osteoarthritis therapy","volume":"17","author":"Wang","year":"2019","journal-title":"Cell Commun. Signal."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/s41580-018-0096-9","article-title":"Crosstalk between metabolism and circadian clocks","volume":"20","author":"Reinke","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1056\/NEJMoa050373","article-title":"Febuxostat compared with allopurinol in patients with hyperuricemia and gout","volume":"353","author":"Becker","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"75","DOI":"10.5483\/BMBRep.2024-0155","article-title":"Wnt5a exacerbates pathological bone features and trabecular bone loss in curdlan-injected SKG mice via osteoclast activation","volume":"58","author":"Whangbo","year":"2025","journal-title":"BMB Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.trsl.2015.06.010","article-title":"Wnt5a is expressed in spondyloarthritis and exerts opposite effects on enthesis and bone in murine organ and cell cultures","volume":"166","author":"Bougault","year":"2015","journal-title":"Transl. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s10067-020-05272-4","article-title":"Comparison of efficacy and safety of urate-lowering therapies for hyperuricemic patients with gout: A meta-analysis of randomized, controlled trials","volume":"40","author":"Fan","year":"2021","journal-title":"Clin. Rheumatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/j.semarthrit.2020.04.011","article-title":"Pegloticase treatment of chronic refractory gout: Update on efficacy and safety","volume":"50","author":"Schlesinger","year":"2020","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/acr.24180","article-title":"2020 American College of Rheumatology Guideline for the Management of Gout","volume":"72","author":"FitzGerald","year":"2020","journal-title":"Arthritis Care Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.25.022106.141627","article-title":"Horror autoinflammaticus: The molecular pathophysiology of autoinflammatory disease","volume":"27","author":"Masters","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1039\/D1BM01179K","article-title":"Injectable thioketal-containing hydrogel dressing accelerates skin wound healing with the incorporation of reactive oxygen species scavenging and growth factor release","volume":"10","author":"An","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s10067-015-3105-9","article-title":"Genetic variation in the ABCG2 gene is associated with gout risk in the Chinese Han population","volume":"35","author":"Jiri","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13018-023-03585-z","article-title":"A metabonomic study to explore potential markers of asymptomatic hyperuricemia and acute gouty arthritis","volume":"18","author":"Wang","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1136\/annrheumdis-2014-206397","article-title":"Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: A dual energy CT study","volume":"74","author":"Dalbeth","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Yang, Y., Guo, Y., Yu, S., and Zou, B. (2022). Computed tomography and magnetic resonance imaging findings in gouty arthritis involving large joints of the upper extremities. BMC Med. Imaging, 22.","DOI":"10.1186\/s12880-022-00894-3"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Qing, Y.F., Zheng, J.X., Tang, Y.P., Dai, F., Dong, Z.R., and Zhang, Q.B. (2021). LncRNAs Landscape in the patients of primary gout by microarray analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0232918"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"20552076221149651","DOI":"10.1177\/20552076221149651","article-title":"Digital twin in healthcare: Recent updates and challenges","volume":"9","author":"Sun","year":"2023","journal-title":"Digit. Health"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nnano.2012.212","article-title":"Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions","volume":"8","author":"Parodi","year":"2013","journal-title":"Nat. Nanotechnol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s12951-024-03046-7","article-title":"A ROS-responsive hydrogel encapsulated with matrix metalloproteinase-13 siRNA nanocarriers to attenuate osteoarthritis progression","volume":"23","author":"Wang","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"102103","DOI":"10.1016\/j.mtbio.2025.102103","article-title":"Dual-functional ROS-responsive hydrogel alleviates temporomandibular joint osteoarthritis by enhancing cartilage repair and mitigating inflammation","volume":"33","author":"Kuang","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.aaf2403","article-title":"Visualization and analysis of gene expression in tissue sections by spatial transcriptomics","volume":"353","author":"Vickovic","year":"2016","journal-title":"Science"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/s41592-022-01409-2","article-title":"Museum of spatial transcriptomics","volume":"19","author":"Moses","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1056\/NEJMra1510062","article-title":"Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both","volume":"377","author":"Woodcock","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6133","DOI":"10.1002\/sim.9175","article-title":"Sample size re-estimation in clinical trials","volume":"40","author":"Wang","year":"2021","journal-title":"Stat. Med."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Dipalma, G., Inchingolo, A.M., Inchingolo, F., Palumbo, I., Riccaldo, L., Guglielmo, M., Morolla, R., Palermo, A., Marinelli, G., and Inchingolo, A.D. (2025). The Precision Paradigm in Periodontology: A Multilevel Framework for Tailored Diagnosis, Treatment, and Prevention. J. Pers. Med., 15.","DOI":"10.3390\/jpm15090440"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1097\/RLI.0000000000000879","article-title":"Assessing the Sensitivity of Dual-Energy Computed Tomography 3-Material Decomposition for the Detection of Gout","volume":"57","author":"Tse","year":"2022","journal-title":"Investig. Radiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"112969","DOI":"10.1016\/j.intimp.2024.112969","article-title":"Could P2X7 receptor be a potencial target in neonatal sepsis?","volume":"142","author":"Fialho","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/annrheumdis-2014-206564","article-title":"Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra","volume":"75","author":"Cleophas","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1038\/s41598-017-04127-4","article-title":"Replication of Gout\/Urate Concentrations GWAS Susceptibility Loci Associated with Gout in a Han Chinese Population","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1161\/CIRCGENETICS.109.934455","article-title":"Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors","volume":"3","author":"Yang","year":"2010","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.pathol.2021.09.001","article-title":"The epigenome: Key to understanding and predicting gout flares","volume":"53","author":"Wolyncewicz","year":"2021","journal-title":"Pathology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.apsb.2023.11.013","article-title":"Commentary: Gut microbiota reduce the risk of hyperuricemia and gout in the human body","volume":"14","author":"Wang","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nri.2016.42","article-title":"Gut microbiota, metabolites and host immunity","volume":"16","author":"Rooks","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Li, Z., Su, Y., Su, H., Pan, J., Li, S., Lu, L., Ji, G., and Xu, H. (2025). Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer. J. Adv. Res.","DOI":"10.1016\/j.jare.2025.08.031"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1136\/annrheumdis-2014-206966","article-title":"Alpha-1-anti-trypsin-Fc fusion protein ameliorates gouty arthritis by reducing release and extracellular processing of IL-1\u03b2 and by the induction of endogenous IL-1Ra","volume":"75","author":"Joosten","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1189\/jlb.3A1015-453RRR","article-title":"Dietary fiber and the short-chain fatty acid acetate promote resolution of neutrophilic inflammation in a model of gout in mice","volume":"101","author":"Vieira","year":"2017","journal-title":"J. Leucoc. Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.cell.2024.01.048","article-title":"The CARD8 inflammasome dictates HIV\/SIV pathogenesis and disease progression","volume":"187","author":"Wang","year":"2024","journal-title":"Cell"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Oliviero, F., and Scanu, A. (2017). How Factors Involved in the Resolution of Crystal-Induced Inflammation Target IL-1\u03b2. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00164"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Arts, R.J.W., Joosten, L.A.B., and Netea, M.G. (2018). The Potential Role of Trained Immunity in Autoimmune and Autoinflammatory Disorders. Front. Imunol., 9.","DOI":"10.3389\/fimmu.2018.00298"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/gutjnl-2015-309728","article-title":"The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia","volume":"65","author":"Schuijt","year":"2016","journal-title":"Gut"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1136\/gutjnl-2015-310746","article-title":"Fungal microbiota dysbiosis in IBD","volume":"66","author":"Sokol","year":"2017","journal-title":"Gut"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/BOR.0000000000000142","article-title":"Use of ultrasound for diagnosis and monitoring of outcomes in crystal arthropathies","volume":"27","author":"Grassi","year":"2015","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.1038\/s41467-018-06318-7","article-title":"Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations","volume":"9","author":"MacParland","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41576-019-0093-7","article-title":"Integrative single-cell analysis","volume":"20","author":"Stuart","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s13075-015-0592-7","article-title":"The metastatic tumor antigen 1-transglutaminase-2 pathway is involved in self-limitation of monosodium urate crystal-induced inflammation by upregulating TGF-\u03b21","volume":"17","author":"Yen","year":"2015","journal-title":"Arthritis Res. Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"817","DOI":"10.3899\/jrheum.220635","article-title":"Clustering Patients With Gout Based on Comorbidities and Biomarkers: A Cross-Sectional Study","volume":"50","author":"Alduraibi","year":"2023","journal-title":"J. Rheumatol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.3899\/jrheum.141164","article-title":"Imaging as an Outcome Measure in Gout Studies: Report from the OMERACT Gout Working Group","volume":"42","author":"Grainger","year":"2015","journal-title":"J. Rheumatol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1080\/10543406.2013.857238","article-title":"Adaptive designs for confirmatory clinical trials with subgroup selection","volume":"24","author":"Stallard","year":"2014","journal-title":"J. Biopharm. Stat."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41584-020-00533-7","article-title":"Mechanisms and therapeutic implications of cellular senescence in osteoarthritis","volume":"17","author":"Coryell","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"e14554","DOI":"10.7717\/peerj.14554","article-title":"The biomarkers discovery of hyperuricemia and gout: Proteomics and metabolomics","volume":"11","author":"Wu","year":"2023","journal-title":"PeerJ"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s00393-017-0341-1","article-title":"Dual-Energy-Computertomographie-Diagnostik bei Gicht Dual-energy computed tomography diagnostics for gout","volume":"76","author":"Rech","year":"2017","journal-title":"Z. Rheumatol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1016\/S0140-6736(21)00569-9","article-title":"Gout","volume":"397","author":"Dalbeth","year":"2021","journal-title":"Lancet"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/nrrheum.2014.139","article-title":"Screening for hyperuricaemia and gout: A perspective and research agenda","volume":"10","author":"Stamp","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3109\/14397595.2014.964823","article-title":"The rs7517847 polymorphism in the IL-23R gene is associated with gout in a Chinese Han male population","volume":"25","author":"Liu","year":"2015","journal-title":"Mod. Rheumatol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Yang, R., Dove, A., Li, X., Yang, H., Li, S., Wang, J., Li, W.D., Zhao, H., and Xu, W. (2022). Healthy lifestyle counteracts the risk effect of genetic factors on incident gout: A large population-based longitudinal study. BMC Med., 20.","DOI":"10.1186\/s12916-022-02341-0"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1093\/rheumatology\/keaa366","article-title":"Ultrasound for the diagnosis of gout-the value of gout lesions as defined by the Outcome Measures in Rheumatology ultrasound group","volume":"60","author":"Fana","year":"2021","journal-title":"Rheumatology"},{"key":"ref_143","first-page":"831","article-title":"Diagnosis, treatment, and prevention of gout","volume":"90","author":"Hainer","year":"2014","journal-title":"Am. Fam. Physician"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1002\/art.39107","article-title":"A Role for Gut Microbiota and the Metabolite-Sensing Receptor GPR43 in a Murine Model of Gout","volume":"67","author":"Vieira","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1002\/art.39654","article-title":"Impact of Febuxostat on Renal Function in Gout Patients with Moderate-to-Severe Renal Impairment","volume":"68","author":"Saag","year":"2016","journal-title":"Arthritis Rheumatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1523\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:13:11Z","timestamp":1770354791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":145,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031523"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031523","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]}}}