{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:24:09Z","timestamp":1783085049707,"version":"3.54.6"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Traditional Chinese medicine (TCM) syndrome differentiation guides personalized treatment; however, its biological basis remains objectively uncharacterized in dermatology, hindering integration with modern precision medicine. Its biological basis remains elusive, particularly in dermatology, hindering its integration with modern precision medicine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate whether major TCM Image Syndrome are associated with distinct, quantifiable multi-dimensional skin imaging phenotypes and to develop a machine learning model integrating these features to predict treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A prospective observational study was conducted on 60 patients with moderate to severe facial photodamage. Participants were classified into one of four TCM syndromes\n                      <jats:italic>\u2014liver\u2013kidney Yin deficiency, liver Qi stagnation, spleen deficiency with dampness,<\/jats:italic>\n                      and\n                      <jats:italic>Qi stagnation and blood stasis<\/jats:italic>\n                      \u2014through consensus diagnosis by two senior TCM physicians. Baseline multi-modal facial imaging was performed using the CBS system or equivalent, quantifying features across four dimensions: pigmentation\/damage (UV spots and brown spots), vascularity (red areas), texture (pores and skin smoothness), and porphyrin fluorescence. Patients then underwent a standardized 12-week intervention protocol. Treatment response was dichotomized as \u201ceffective\u201d (The area and severity index of hyperpigmentation spots (MASI reduction index) \u2265 30%) or \u201cineffective\u201d (MASI reduction index &amp;lt; 30%) based on standardized criteria. Statistical analyses included multivariate analysis of variance (MANOVA) for group comparisons, principal component analysis (PCA) for the exploration of phenotype structure, and machine learning (XGBoost and random forest) for predictive modeling. These models were evaluated using the receiver operating characteristic area under the curve (ROC-AUC) and were interpreted via SHapley Additive exPlanations (SHAP) values.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significant overall differences in skin imaging profiles were found among the four TCM syndromes (MANOVA,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Specific patterns emerged: the spleen deficiency with dampness group exhibited the highest median UV spot counts, while the liver\u2013kidney Yin deficiency group showed the most pronounced brown spot intensity. PCA revealed that the first two principal components (cumulative variance: 58.9%) effectively separated the syndromes in a low-dimensional space. The integrative prediction model, combining TCM syndrome labels and all quantified imaging features, achieved exceptional performance (AUC: 0.99; 95% CI: 0.98\u20131.00). SHAP analysis identified UV spot metrics and the spleen deficiency with dampness syndrome label as the top predictive features.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides empirical evidence that TCM syndromes correspond to specific, objective multi-dimensional skin phenotype patterns. Furthermore, an integrative model combining TCM diagnosis and quantitative imaging biomarkers can predict therapeutic outcomes with high accuracy. These findings help bridge TCM theory and modern biophysical assessment, paving the way for a data-driven, personalized approach in dermatology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1810077","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:46:54Z","timestamp":1780030014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative analysis links traditional Chinese medicine syndrome differentiation to multi-dimensional skin phenotypes and predicts therapeutic response in photographs"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhili","family":"Dou","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Yan\u2018an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingmei","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Yan\u2018an University","place":["Yan\u2019an, China"]},{"name":"The Affiliated Hospital of Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Tan","sequence":"additional","affiliation":[{"name":"The Department of Traditional Chinese Medicine of the Affiliated Hospital of Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Jing","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Department of Affiliated Hospital of Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Hui","sequence":"additional","affiliation":[{"name":"The Department of Traditional Chinese Medicine of the Affiliated Hospital of Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Yan\u2018an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixi","family":"Li","sequence":"additional","affiliation":[{"name":"The Department of Traditional Chinese Medicine of the Affiliated Hospital of Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehao","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Yan\u2018an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlei","family":"Liu","sequence":"additional","affiliation":[{"name":"The Department of Traditional Chinese Medicine of the Affiliated Hospital of Yan\u2019an University","place":["Yan\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.2147\/CCID.S44686","article-title":"Effect of the sun on visible clinical signs of aging in Caucasian skin","volume":"6","author":"Flament","year":"2013","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1034\/j.1600-0625.2002.110502.x","article-title":"Intrinsic aging vs. photographing: a comparative histopathological, immunohistochemical, and ultrastructural study of skin","volume":"11","author":"El-Domyati","year":"2002","journal-title":"Exp Dermatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.7150\/ijbs.45538","article-title":"Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): a review and perspective","volume":"16","author":"Yang","year":"2020","journal-title":"Int J Biol Sci"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"6010","DOI":"10.1360\/csb-2025-5119","article-title":"Syndrome representation, biology, and research on traditional Chinese medicine","volume":"70","author":"Zhang","year":"2025","journal-title":"Chin Sci Bull"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2381","DOI":"10.3390\/diagnostics14212381","article-title":"Different pathways of skin aging: objective instrumental evaluation","volume":"14","author":"Musolff","year":"2024","journal-title":"Diagnostics (Basel)"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"105298","DOI":"10.1016\/j.pdpdt.2025.105298","article-title":"Revealing the invisible: in vivo imaging for photographing therapies- review of the literature","volume":"56","author":"Korponai","year":"2025","journal-title":"Photodiagn Photodyn Ther"},{"key":"ref7","first-page":"153","author":"Pan","year":"2023"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"410","DOI":"10.4314\/ahs.v24i3.45","article-title":"A unique approach for investigating skin lesions and their relationship with TCM syndrome differentiation in alopecia areata","volume":"24","author":"Zhang","year":"2024","journal-title":"Afr Health Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"104292","DOI":"10.1016\/j.pdpdt.2024.104292","article-title":"Deep learning-assisted multispectral imaging for early screening of skin diseases","volume":"48","author":"Jiang","year":"2024","journal-title":"Photodiagn Photodyn Ther"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"116306","DOI":"10.1016\/j.jep.2023.116306","article-title":"Network pharmacology is a promising approach to reveal the pharmacological mechanism of Chinese medicine formulas","volume":"309","author":"Zhao","year":"2023","journal-title":"J Ethnopharmacol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nature21056","article-title":"Dermatologist-level classification of skin cancer with deep neural networks","volume":"542","author":"Esteva","year":"2017","journal-title":"Nature"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e4","DOI":"10.1017\/erm.2018.3","article-title":"What has traditional Chinese medicine delivered for modern medicine?","volume":"20","author":"Wang","year":"2018","journal-title":"Expert Rev Mol Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1001\/archderm.1992.01680130061006","article-title":"A photonumeric scale for the assessment of cutaneous photodamage","volume":"128","author":"Griffiths","year":"1992","journal-title":"Arch Dermatol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/jdv.16044","article-title":"European dermatology forum guidelines on topical photodynamic therapy 2019 part 2: emerging indications - field cancerization, photorejuvenation and inflammatory\/infective dermatoses","volume":"34","author":"Morton","year":"2020","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"276","DOI":"10.11613\/BM.2012.031","article-title":"Interrater reliability: the kappa statistic","volume":"22","author":"McHugh","year":"2012","journal-title":"Biochem Med (Zagreb)"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1111\/jocd.12081","article-title":"Objective assessment of facial skin aging and the associated environmental factors in Japanese monozygotic twins","volume":"13","author":"Ichibori","year":"2014","journal-title":"J Cosmet Dermatol"},{"key":"ref17","first-page":"20150202","article-title":"Principal component analysis: a review and recent developments","volume":"374","author":"Jolliffe","year":"2016","journal-title":"Philos Trans A Math Phys Eng Sci"},{"key":"ref18","article-title":"A unified approach to interpreting model predictions","volume-title":"31st Conference on Neural Information Processing Systems (NIPS 2017)","author":"Lundberg","year":"2017"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/j.jep.2011.08.045","article-title":"An integrative approach of linking traditional Chinese medicine pattern classification and biomedicine diagnosis","volume":"141","author":"Lu","year":"2012","journal-title":"J Ethnopharmacol"},{"key":"ref20","volume-title":"Research on the Correlation between \"Microscopic\" Changes of Female Melasma Lesions and Traditional Chinese Medicine Syndrome Differentiation","author":"Yang","year":"2012"},{"key":"ref21","first-page":"288","article-title":"How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for clinical practice","volume-title":"Int J Cosmet Sci","author":"Darlenski","year":"2023"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.jgg.2021.04.002","article-title":"Gut microbiota, inflammation, and molecular signatures of host response to infection","volume":"48","author":"Gou","year":"2021","journal-title":"J Genet Genomics"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1111\/jdv.17432","article-title":"Adult skin acute stress responses to short-term environmental and internal aggression from exposome factors","volume":"35","author":"Passeron","year":"2021","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000003532","article-title":"Metabolomic profiling reveals distinct metabolic patterns and a potential circulating biomarker in pre-COPD","author":"Ren","year":"2025","journal-title":"Chin Med J"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1056\/nejmra1814259","article-title":"Machine learning in medicine","volume":"380","author":"Rajkomar","year":"2019","journal-title":"N Engl J Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1055\/s-0030-1250450","article-title":"Systems biology-based diagnostic principles as pillars of the bridge between Chinese and Western medicine","volume":"76","author":"van der Greef","year":"2010","journal-title":"Planta Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s42256-019-0138-9","article-title":"From local explanations to global understanding with explainable AI for trees","volume":"2","author":"Lundberg","year":"2020","journal-title":"Nat Mach Intell"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"g7594","DOI":"10.1136\/bmj.g7594","article-title":"Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement","volume":"350","author":"Collins","year":"2015","journal-title":"BMJ"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1093\/eurheartj\/ehu207","article-title":"Towards better clinical prediction models: seven steps for development and an ABCD for validation","volume":"35","author":"Steyerberg","year":"2014","journal-title":"Eur Heart J"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1195272","DOI":"10.3389\/fphys.2023.1195272","article-title":"Skin aging from mechanisms to interventions: focusing on dermal aging","volume":"14","author":"Shin","year":"2023","journal-title":"Front Physiol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2229","DOI":"10.1056\/NEJMsb1503104","article-title":"Precision medicine--personalized, problematic, and promising","volume":"372","author":"Jameson","year":"2015","journal-title":"N Engl J Med"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.jep.2012.01.033","article-title":"Syndrome differentiation in modern research of traditional Chinese medicine","volume":"140","author":"Jiang","year":"2012","journal-title":"J Ethnopharmacol"}],"updated-by":[{"DOI":"10.3389\/fvets.2026.1869864","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000}},{"DOI":"10.3389\/fmed.2026.1895485","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000}}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1810077\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T12:38:17Z","timestamp":1783082297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1810077\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":32,"alternative-id":["10.3389\/fmed.2026.1810077"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1810077","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1810077"}}