From "Three-Cause Theory" to "Three-Dimensional Model": construction and empirical study of a methodological system for disease-syndrome combination research

Syndrome differentiation and treatment is the core feature and strength of traditional Chinese medicine (TCM), with syndrome serving as the cornerstone of TCM diagnosis and treatment. However, under the dominance of the modern medical research paradigm, a considerable number of current TCM studies, especially basic experimental research, exhibit a tendency to "emphasize disease while neglecting syndrome," "have disease without syndrome," or even "abandon medical theory while retaining only drugs." This conceptual deviation causes TCM research to lose its distinctive characteristics, and fails to reflect the efficacy evaluation of TCM′s advantages. In the long run, it may further marginalize the core thinking of TCM within the scientific research system, thereby eroding its foundation. Strengthening and promoting the "disease-syndrome combination" research model is the key to resolving this dilemma and achieving the preservation and innovation of TCM. Through over three decades of continuous efforts, our team has explored and put into practice a disease-syndrome combination research model centered on the "Three-Cause Theory" and integrating clinical and basic researches. At the clinical research level, this model integrates macroscopic four-diagnosis information with microscopic physicochemical indicators, utilizes large-sample data and artificial intelligence method, and constructs an objective and quantifiable syndrome diagnosis model. At the basic research level, grounded in the "Three-Cause Theory" (pathogenic factors, genetic constitution, and disease stage), we have established a "Three-Dimensional Model" (macro sign combinations, micro indicator feature combinations, and formula-based counter-evidence) for the preparation and evaluation of disease-syndrome combination animal models, providing a reproducible and verifiable experimental carrier for modern scientific interpretations of TCM theories. Practice has demonstrated that this system can effectively evaluate the efficacy of Chinese herbal formulas in concurrently treating both the disease and syndrome, while also advancing the modern scientific exposition of TCM′s connotation. The establishment of this methodology helps propel syndrome research into a new stage that is modelable, predictable, and verifiable, offering referable pathways and methodological references for the modern interpretation of TCM principles.