Objective To summarize the common rules of clinical application of Traditional Chinese and Zhuang Medicines for treating diseases in Guangxi prestigious doctors of Traditional Chinese Medicine by employing data mining technique. Methods Clinical empirical prescriptions of various Guangxi prestigious doctors of Traditional Chinese Medicine were retrieved from Hundred Empirical Prescriptions of Guangxi Hundred Prestigious Doctors of Traditional Chinese Medicine and China National Knowledge Infrastructure database, and then database of prescriptions was established. Analyses of disease groups distribution concerned, drug use frequency, association rule, systematic cluster, principle component factors, and complex network were performed on the data of prescriptions and d+rugs retrieved. Results A total of 149 clinical empirical prescriptions of 99 Guangxi prestigious doctors of Traditional Chinese Medicine were enrolled, which were used to treat diseases throughout the common diseases of Traditional Chinese Medicine. Prescriptions included 333 flavors of drugs in total, containing 291 flavors of Traditional Chinese Medicines, 73 flavors of Zhuang Medicines, 31 flavors of overlapping drugs with Traditional Chinese and Zhuang Medicines. There were 20 categories of high⁃frequency drugs (use frequency≥14 times) in total, and the top 5 most frequently used Traditional Chinese Medicines were licorice, Poria cocos, Atractylodes macrocephala, Astragalus membranaceus, and Angelica sinensis; furthermore, the top 5 most frequently used Zhuang Medicines were Citrus reticulata, Panax notoginseng, Caulis spatholobi, earthworm, and Rhizoma dioscoreae. Through association rule analysis, there were 12 groups of core drug pairs and 19 groups of core triple⁃combination medicines. The systematic cluster analysis had divided high⁃frequency drugs into 5 categories. The principle component factors analysis could extract 8 common factors. The results of complex network analysis interpreted that the combination of herbal ingredients between Atractylodes macrocephala, Poria cocos, and licorice exerted the strongest correlation. Conclusion Diseases of digestive system, qi⁃blood body fluids system, and limbs and meridians system in Guangxi regions frequently occurred, and syndromes mainly belong to deficiency in nature and excess in superficiality. Doctors often use Traditional Chinese and Zhuang Medicines to share clinical syndromes, and most of the drugs are local medicinal materials. Combined with regional characteristics and physical characteristics of residents in Guangxi, adjust measures to local conditions, syndrome differentiation and treatment were conducted, and the main therapeutic principle is tonifying deficiency and dispelling dampness, taking into account the three methods of moving qi, increasing urine excretion, and promoting blood circulation throughout treatment. The drug combination of Atractylodes macrocephala, Poria cocos, and licorice exert the strongest correlation. 

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