Biomarker profiles across traditional Chinese medicine syndromes and exploratory discrimination of internal toxin syndrome in stable post-PCI patients: a cross-sectional study
4 affiliations
- 1Department of Cardiology, Dongzhimen Hospital, Beijing University of Chinese Medicine
- 2Department of Cardiology, Shanghai Minhang District Hospital of Integrated Traditional Chinese and Western Medicine
- 3Department of Cardiology, Shanghai Minhang District Hospital of Traditional Chinese Medicine
- 4Department of Cardiology (Ward II), Xi'an Hospital of Traditional Chinese Medicine
Abstract
Background: The relationship between persistent post-percutaneous coronary intervention (PCI) inflammation and Traditional Chinese Medicine (TCM) syndromes remains incompletely characterized.
Objective: To investigate associations between TCM syndrome scores and circulating inflammatory biomarkers, NR1D1, and CLCF1, and explore concurrent discrimination of Internal Toxin syndrome in stable post-PCI coronary heart disease.
Methods: This single-center, two-stage cross-sectional study enrolled 133 patients. Expert syndrome classifications were compared with outputs from the Traditional Chinese Medicine Syndrome Standardization Database (TTCMSSD). Participants assigned to one of five core single syndromes, selected by frequency and theoretical relevance, underwent biomarker analyses. Spearman's correlations assessed score–biomarker associations. Logistic regression and receiver operating characteristic analyses evaluated concurrent Internal Toxin discrimination. Given only 14 Internal Toxin cases, the selected four-cytokine model was refitted using Firth's penalized logistic regression and evaluated through bootstrap internal validation.
Results: The biomarker cohort comprised 86 participants: Qi Deficiency ( n = 28), Blood Stasis ( n = 22), Internal Toxin ( n = 14), Phlegm Turbidity ( n = 12), and Heat Accumulation ( n = 10). Expert–TTCMSSD agreement was substantial (Cohen's κ = 0.688, 95% CI 0.599–0.768; P < 0.001). The Internal Toxin group showed higher TNF-α, IL-1β, and IL-6 and lower IL-10 than selected comparison groups. Scores showed syndrome-specific inflammatory associations. All five scores correlated negatively with plasma NR1D1 and positively with serum CLCF1; all 10 associations remained significant after Benjamini–Hochberg correction ( q < 0.001). IL-1β had the largest single-marker AUC (0.894, 95% CI 0.828–0.960). The four-cytokine Firth model comprising IL-6, IL-10, IL-1β, and TNF-α achieved an apparent AUC of 0.952 and an optimism-corrected AUC of 0.942.
Conclusion: TCM syndrome scores were associated with inflammatory profiles and NR1D1/CLCF1 concentrations in stable post-PCI patients. The four-cytokine model showed promising internal concurrent discrimination of Internal Toxin syndrome but remains exploratory and hypothesis-generating, not clinically validated. Larger prospective studies with independent external validation are needed to establish temporal, causal, and clinical relevance.
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BibTeX
@article{li2026biomarker,
title = {{Biomarker profiles across traditional Chinese medicine syndromes and exploratory discrimination of internal toxin syndrome in stable post-PCI patients: a cross-sectional study}},
author = {Dan Li and Li Yang and Jingen Li and Jia Liu and Peifen Chang},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = nov,
doi = {10.3389/fcvm.2026.1877766},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1877766/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Biomarker profiles across traditional Chinese medicine syndromes and exploratory discrimination of internal toxin syndrome in stable post-PCI patients: a cross-sectional study
AU - Dan Li
AU - Li Yang
AU - Jingen Li
AU - Jia Liu
AU - Peifen Chang
PY - 2026
DA - 2026/11/04
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1877766
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1877766/full
AB - Background: The relationship between persistent post-percutaneous coronary intervention (PCI) inflammation and Traditional Chinese Medicine (TCM) syndromes remains incompletely characterized. Objective: To investigate associations between TCM syndrome scores and circulating inflammatory biomarkers, NR1D1, and CLCF1, and explore concurrent discrimination of Internal Toxin syndrome in stable post-PCI coronary heart disease. Methods: This single-center, two-stage cross-sectional study enrolled 133 patients. Expert syndrome classifications were compared with outputs from the Traditional Chinese Medicine Syndrome Standardization Database (TTCMSSD). Participants assigned to one of five core single syndromes, selected by frequency and theoretical relevance, underwent biomarker analyses. Spearman's correlations assessed score–biomarker associations. Logistic regression and receiver operating characteristic analyses evaluated concurrent Internal Toxin discrimination. Given only 14 Internal Toxin cases, the selected four-cytokine model was refitted using Firth's penalized logistic regression and evaluated through bootstrap internal validation. Results: The biomarker cohort comprised 86 participants: Qi Deficiency ( n = 28), Blood Stasis ( n = 22), Internal Toxin ( n = 14), Phlegm Turbidity ( n = 12), and Heat Accumulation ( n = 10). Expert–TTCMSSD agreement was substantial (Cohen's κ = 0.688, 95% CI 0.599–0.768; P < 0.001). The Internal Toxin group showed higher TNF-α, IL-1β, and IL-6 and lower IL-10 than selected comparison groups. Scores showed syndrome-specific inflammatory associations. All five scores correlated negatively with plasma NR1D1 and positively with serum CLCF1; all 10 associations remained significant after Benjamini–Hochberg correction ( q < 0.001). IL-1β had the largest single-marker AUC (0.894, 95% CI 0.828–0.960). The four-cytokine Firth model comprising IL-6, IL-10, IL-1β, and TNF-α achieved an apparent AUC of 0.952 and an optimism-corrected AUC of 0.942. Conclusion: TCM syndrome scores were associated with inflammatory profiles and NR1D1/CLCF1 concentrations in stable post-PCI patients. The four-cytokine model showed promising internal concurrent discrimination of Internal Toxin syndrome but remains exploratory and hypothesis-generating, not clinically validated. Larger prospective studies with independent external validation are needed to establish temporal, causal, and clinical relevance.
SN - 2297-055X
ER -