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Early detection and timely treatment can effectively improve the prognosis of DR. Metabolomic analysis provides a powerful tool for studying pathophysiological processes. Conducting metabolomic analyses on DR\u2010related biofluids helps identify differential metabolic expressions during disease progression, thereby discovering potential biomarkers to support clinical diagnosis and treatment. Here, an innovative workflow for vitreous liquid analysis is established, and a machine learning\u2010based DR analysis platform integrating vitreous liquid metabolic fingerprint (VL\u2010MF) and plasma metabolic fingerprint (P\u2010MF) derived via nanoparticle enhanced laser desorption\/ionization mass spectrometry is developed. Direct VL\u2010MF and P\u2010MF are obtained with desirable reproducibility (coefficient of variation, CV &lt;5%) and remarkable speed (3\u00a0s per sample), and DR patients are distinguished from healthy controls applying dual biofluid\u2010MF with an area under the curve (AUC) of 0.957. Moreover, a biomarker candidate panel from vitreous liquid and plasma with an AUC of 0.945 is constructed and the related metabolic pathways are identified by metabolomics pathway analysis (MetPA). This work offers a powerful multi\u2010biofluid platform that can not only contribute to DR but also provide solid references for other clinical applications.<\/jats:p>","DOI":"10.1002\/smll.202412195","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T04:21:57Z","timestamp":1738038117000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metabolic Fingerprint of Dual Body Fluids Deciphers Diabetic Retinopathy"],"prefix":"10.1002","volume":"21","author":[{"given":"Yihan","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory for Oncogenes and Related Genes School of Biomedical Engineering Institute of Medical Robotics and Med\u2010X Research Institute Shanghai Jiao Tong University  Shanghai 200030 P. R. 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