[New paradigm for identifying pharmacodynamic substances of TCM through knock-out/knock-in technique by integrating traditional efficacy, material basis, and action targets].

TCM is a treasure of Chinese civilization and a potential key to solving modern medical challenges. Research on the pharmacodynamic material basis, action targets, and mechanisms based on the traditional efficacy of TCM has become a consensus. Clarifying the pharmacodynamic material basis of TCM is not only a fundamental issue in TCM research but also a critical step in deciphering the complex TCM systems. However, the complexity of TCM systems poses significant challenges to the research of their pharmacodynamic material basis, leaving the pharmacodynamic material basis of treating diseases in most TCM largely unclear, which greatly limits people's scientific understanding of TCM in treating diseases. Currently, the research on the pharmacodynamic material basis of TCM has formed an interdisciplinary methodological system. Various methods have shown unique advantages, but they all have the common problem of being unable to balance the holistic view of TCM and research precision. The knock-out/knock-in technique can precisely disassemble and controllably integrate the complex TCM system and is a key technique to solve the challenges in the research of TCM material basis. Based on this, this paper proposed a new paradigm for identifying the material basis based on the knock-out/knock-in technique. This paradigm integrates the intrinsic connection among traditional efficacy, material basis, and action targets, aiming to provide new ideas for the research on the material basis of TCM and methodological support for the TCM modernization.