[Mechanism of circadian clock gene-mediated lipid metabolism reprogramming in regulating "inflammation to cancer" transformation of chronic atrophic gastritis and chrono-modulated traditional Chinese medicine intervention research based on theory of "Taiyin disease resolution period"].
Chronic atrophic gastritis(CAG) represents a critical precancerous stage in gastric carcinogenesis, and its pathogenesis involves circadian rhythm disruption, chronic inflammation, and lipid metabolism reprogramming. Employing an integrative Chinese-western medical approach, this study systematically elucidated the molecular mechanisms whereby the core circadian clock gene BMAL1 promotes "inflammation to cancer" transformation through modulating the HIF-1α-FABP axis, driving lipid metabolism reprogramming, exacerbating oxidative stress, and disrupting immune homeostasis. The study revealed that compound traditional Chinese medicine(TCM) formulas(including Huangqi Jianzhong Tang, Xianglian Huazhuo Fang, and Lizhong Tang) intervened in the BMAL1-mediated "circadian-metabolic-immune" network, significantly ameliorated pathological damage to the gastric mucosa, suppressed inflammatory responses, alleviated lipid metabolism disorder, and reversed the "inflammation to cancer" transformation through multi-target effects. The TCM concept of "Taiyin disease resolution period"(21:00-03:00) gave insights into the link between spleen and stomach functions and circadian rhythms, with its therapeutic time window exhibiting remarkable synchronization with BMAL1 expression rhythms. Clinical studies further demonstrated that chronotherapy strategies based on chronopharmacological principles can significantly enhance the therapeutic efficacy of TCM. Based on these findings, the theory of "Taiyin disease resolution period" provides guidance for chronotherapeutic intervention in CAG management. Through innovative integration of modern chronobiology and traditional temporal medicine principles, the study illuminates the central role of the circadian clock gene in the CAG "inflammation to cancer" transformation and emphasizes the potential of the circadian clock and chronotherapy in reversing the "inflammation to cancer" transformation, offering both mechanistic insights and clinically actionable strategies for CAG treatment via chronobiology.