{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:21:02Z","timestamp":1783336862778,"version":"3.54.6"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"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 is central to individualized diagnosis, but its relationship with objective biochemical markers remains insufficiently characterized within explicit frameworks for intervention\u2013analog causal inference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to construct a syndrome load index using confirmatory factor analysis (CFA) and item response theory (IRT), assess measurement invariance, and estimate adjusted intervention\u2013analog associations with lipid and C-reactive protein (CRP) biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective cohort study included 1,472 adults with structured TCM assessments and repeated biochemical measurements over 90\u202fdays. Syndrome load was modeled as a continuous latent variable using CFA\/IRT. A Gaussian generalized propensity score with stabilized inverse probability of treatment weighting, combined with double machine learning cross-fitting, estimated associations with low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and CRP z-scores, as well as corresponding binary abnormality outcomes. Quartiles were used only for descriptive diagnostics. Negative controls, baseline laboratory sensitivity analyses, weight diagnostics, and E-value analyses assessed robustness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CFA\/IRT models demonstrated good fit (CFI\u202f=\u202f0.96, RMSEA\u202f=\u202f0.042) and supported metric\/scalar invariance across both sex and age groups. The emulated contrast represented a 1-standard deviation (SD) difference in baseline syndrome load as an analytic intervention analog, rather than a literal randomization of a latent construct. After weighting, all absolute standardized mean differences (SMDs) were &amp;lt;0.10, the effective sample size was 1,289, and no material positivity violations were observed. A 1-SD higher syndrome load was associated with higher TG z-scores (+0.18; 95%CI: 0.12\u20130.24; approximately +0.20\u202fmmol\/L), LDL-C z-scores (+0.11; 95%CI: 0.05\u20130.18; approximately +0.10\u202fmmol\/L), and CRP z-scores (+0.16; 95%CI: 0.09\u20130.23; approximately +0.31\u202fmg\/L), corresponding to 3\u20135% absolute risk increases in biomarker abnormalities. Baseline laboratory sensitivity analyses yielded attenuated but directionally consistent estimates (TG\u202f+\u202f0.16, LDL-C\u202f+\u202f0.09, CRP\u202f+\u202f0.13 to +0.14 z-score units). Associations were stronger among participants aged \u226565\u202fyears, those with diabetes, or those with body mass index (BMI)\u202f\u2265\u202f28. Negative controls were null, and E-values ranged from 1.54 to 1.92.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Higher syndrome load was consistently associated with dyslipidemia and CRP elevation within an explicit intervention\u2013analog framework. These findings support syndrome objectification and personalized cardiometabolic risk stratification; however, prospective intervention studies are required before concluding that the latent syndrome construct itself is directly modifiable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1789294","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:10:29Z","timestamp":1783336229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intervention\u2013analog association between traditional Chinese medicine syndrome load and lipid\/C-reactive protein biomarkers: a single-center retrospective cohort study using target trial emulation"],"prefix":"10.3389","volume":"13","author":[{"given":"Yu-Xuan","family":"Guo","sequence":"first","affiliation":[{"name":"Center Laboratory Medicine, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University","place":["Urumqi City, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Han","sequence":"additional","affiliation":[{"name":"Center Laboratory Medicine, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University","place":["Urumqi City, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xiang","sequence":"additional","affiliation":[{"name":"Center Laboratory Medicine, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University","place":["Urumqi City, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Center Laboratory Medicine, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University","place":["Urumqi City, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"name":"Center Laboratory Medicine, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University","place":["Urumqi City, Xinjiang Uygur Autonomous Region, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang-Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, The Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Oncology","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.1002\/ar.24821","article-title":"Standardization, objectification, and essence research of traditional Chinese medicine syndrome: a 15-year bibliometric and content 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