Based on the new concept of “Yu-Re Struggling” proposed by Prof. Zhou Zhongying, research was made on “Wu zi syndrome” thereof, forming a new doctrine of disease mechanism, i.e. “Yu Re”. Provided are a systematic introduction to the connotation of “Yu Re”, such as its concept, formation, main pathological changes, classification, therapeutic principles, theoretical framework, as well as relevant clinical experience. Four typical case reports of Prof. Zhou are accompanied, showing clinical advantages of Yu-Re based differentiation in the treatment of refractory internal diseases.