前期研究发现炎症环境导致胆汁酸代谢紊乱、正调控炎症小体信号，而抗炎化合物穿心莲内酯则诱导线粒体自噬、负调控炎症小体信号，并首次发现NF-κB信号的新调控环路。本研究基于这正反调控的2个小分子发现的新环路，探讨新环路在结肠炎-癌转化中的作用及其可供药物调控的关键节点。包括：1）探讨炎症环境下胆汁酸与结肠炎-癌进展的相关关系；炎症调控胆汁酸代谢的信号通路；胆汁酸促进炎症小体信号阻止炎症修复的机理。2）TRAF6/IKK/Parkin新环路的确证；TRAF6调控mitophagy-NLRP3的分子机制；阐明新环路能否影响NF-κB信号、新环路中可供药物调控的位点等。3）结肠炎及炎-癌转化中上述新环路的验证；阐明新环路参与5-FU耐药的机制；临床试验观察穿心莲内酯联合5-FU对结肠癌的疗效及与新环路的相关性。本研究可为炎症向癌症转化的解释提供新的视角，为结肠炎相关结肠癌的预防和治疗提供新的策略。

Our Previous study found that the inflammatory environment could lead to the disorders of bile acid metabolism and positively regulate the inflammasome, Also andrographolide, an anti-inflammatory compound, induced mitochondrial autophagy and negatively regulated inflammasome. We first found a new regulating circuit containing NF-kB. We plan to explore the role of new circuit in colitis-cancer transformation and the key nodes that can be regulated by drugs. Our research include three aspects: 1) Investigate the correlation between bile acids and the colitis-cancer progression in inflammatory environment; The signaling pathways of the bile acids metabolism regulated by inflammation; The mechanism that bile acids prevent inflammation restoration via activating the inflammasome. 2) Confirm the new circuit of TRAF6/IKK/Parkin. To clarify the molecular mechanisms of mitophagy-NLRP3 regulated by TRAF6; to reveal the new circuit whether it can affect NF-κB signaling pathway and the targeting sites that can be regulated by drugs in the circuit. 3) Validate the new circuit in the colitis -cancer transformation. To elucidate the mechanism involved in the new circuit of 5-FU resistance; to observe the correlation of clinical effects of 5-FU combined andrographolide to treat the patients of colorectal cancer and new circuit by clinical trial. This research may provide a new perspective to explain the phenomenon of transformation from inflammation to cancer and provide a new strategy for the prevention and treatment of colitis-associated colon cancer.