根据肝癌肝再生微环境的理论认识和前期工作基础，提出如下科学假说：肝纤维化的异常肝再生微环境是HBeAg阴性CHB患者肝癌发生风险高的重要宿主因素，EMT/MET及其相关信号通路失衡和Hh信号通路紊乱是其肝再生微环境恶化的重要机制，地五养肝胶囊可以通过调控EMT/MET及其相关信号通路失衡和Hh信号通路紊乱而发挥通过改善HBeAg阴性CHB患者肝再生微环境降低肝癌发生风险的作用。本项目在前期研究的基础上，从细胞、动物和HBeAg阴性CHB患者不同层面，采用系统分子生物学的相关技术与方法研究肝再生微环境与肝癌发生发展的相关机制，揭示地五养肝胶囊通过调控EMT/MET及其相关信号通路失衡和Hh信号通路紊乱而发挥改善肝再生微环境降低其肝癌发生风险的作用及其机制，为“肝主生发”（髓生肝，髓失生肝，补肾生髓成肝）的理论创新提供新的实验依据，提高中医药防治肝癌的能力和水平，推动中医学术的发展。

According to the theory of liver regeneration microenvironment of liver cancer and the basis of previous work, we propose the following scientific hypothesis: Abnormal liver regeneration microenvironment of liver fibrosis is an important host factor for the high risk of liver cancer in patients with HBeAg-negative chronic hepatitis B (CHB), the imbalance of EMT/MET and its related signal pathways and the disorder of Hedgehog signaling pathway are important mechanisms of the deterioration of microenvironment of liver regeneration. Diwu Yanggan Capsule can can reduce the risk of liver cancer by regulating the imbalance of EMT/MET and its related signaling pathways and disorder of Hh signaling pathway to improve the microenvironment of liver regeneration in patients with HBeAg-negative CHB. Based on the previous studies, we studied the related mechanisms of liver regeneration microenvironment and the occurrence and development of liver cancer from different aspects of cell, animal and HBeAg-negative CHB patients by techniques and methods of system molecular biology. The purpose of this study is to reveal the effect and mechanism of Diwu Yanggan Capsule on reducing the risk of liver cancer by regulating the imbalance of EMT/MET and its related signaling pathways and disorder of Hh signaling pathway. It will provide a new experimental basis for the theoretical innovation of “the liver governing growth”(“marrow stem cells differentiate into liver cells”, “marrow stem cells failing to differentiate into liver cells” and “tonifying the kidney to promote liver regeneration and repair by effecting stem cells and their microenvironment”), which will help to improve the ability and level of Chinese medicine in preventing and treating liver cancer and promote the academic progress of Chinese medicine.