Accurately performed thermoregulation is life-important for the human body. Therefore, a relatively narrow temperature range of 36.5–37 °C, which all our biochemical reactions are adapted to, is rigorously kept by the body allowing for the most effective kinetics of all physiological processes. In contrast, feeling inappropriately cold or too hot in the environment with comfortable temperature ranges are symptoms of an altered or even disordered thermoregulation described for a number of syndromes as well as patient cohorts. The rationale of the paper is to contribute to the paradigm shift from reactive to proactive healthcare considering thermoregulation deficits as an important diagnostic and prognostic indicator to be explored and utilized for patient phenotyping and stratification followed by tailored treatment algorithms in primary and secondary care. The conceptual framework of Yin–Yang/Cold–Heat syndromes in Traditional Chinese Medicine (TCM) provides a holistic description of physiological balance, adaptability, and pathological deviation. Recent advances in molecular physiology and biotechnology now permit these ancient classifications to be reframed as quantifiable, systems-level biological states. This review integrates thermosensitive transient receptor potential (TRP) channels with ion-channel networks, inflammatory signaling, and emerging multiomics regulation to reinterpret Cold–Heat syndromes through a modern biotechnological lens. We further incorporate the paracentral dogma concept—highlighting epigenetic, proteomic, and glycomic regulation beyond the classical DNA–RNA–protein axis—to explain how non-template-driven molecular layers dynamically tune TRP channel sensitivity and downstream inflammatory balance. Drawing on advances in genomics, proteomics, glycomedicine, and systems engineering, we propose that Cold–Heat states represent stable yet reversible molecular attractors shaped by environmental exposure, metabolic state, and post-translational modification. Finally, we outline translational opportunities including TRP-based biosensors, epigenetic, protein and glycan biomarkers, and AI-driven Cold–Heat stratification platforms. This integrative framework positions TCM-inspired pattern differentiation as a scalable systems biology paradigm with direct relevance to predictive, preventive and personalized healthcare. A left–right Cold (Yin) to Heat (Yang) continuum integrates layered regulation from genetics, epigenetics, and glycobiology through TRP/ion channels to cytokine-driven clinical phenotypes, visually unifying TCM theory with modern molecular biotechnology.
Wang et al. (2026) studied this question.