| Objective:Guided by TCM theory,a computational model of analogous formulas for insomnia was constructed by using the method of similarity calculation of isomorphic features.Based on the verification of the robustness of this model,the model of analogous formulas for insomnia was used to predict the possible formulas with insomnia treatment function in the Classic formula of the Treatise on Typhoid,which provides a method for the excavation of analogous formulas for insomnia and a new idea for the modern research of disease-based analogous formulas.Methods:1.All prescriptions in the Dictionary of Traditional Chinese Medicine were searched,inclusion and exclusion criteria were established,and prescriptions with efficacy in treating insomnia were screened.The names of the drugs were unified according to the Chinese Pharmacopoeia(2020edition)as the standard,and their four qi,five tastes,attribution and efficacy were assigned separately to establish a database of analogous formulas for the treatment of insomnia.2.The standard formulas for the treatment of "sleeplessness"(insomnia)in the 13 th Five-Year Plan National Textbook of Internal Medicine were Gentian Diarrhea Liver Soup,Huang Lian Wen Bile Soup,Gui Qi Tang,Liu Wei Di Huang Wan combined with Jiaotai Wan,and An Shen Ding Zhi Wan combined with Sour Date Ren Tang.A multimodal database of five standard prescriptions was established.The insomnia prescription database and the five standard prescription databases were used to calculate the similarity using the cosine similarity model to construct five models for different TCM symptoms of analogous formulas for insomnia.3.The threshold value of the model was initially determined using the empirical method.Medical cases of insomnia from ancient and modern famous authors that were consistent with the main treatment types of the five standard prescriptions were collected,and a database of medical prescriptions was established respectively,and the similarity of isomorphic features was calculated with the corresponding standard prescriptions to determine the appropriate threshold range,and the calculation model of analogous formulas for insomnia was revised and improved.4.95 prescriptions in the Typhoid that did not have clear efficacy in treating insomnia were standardized and a database was established.Using the model of analogous formulas for insomnia,the prescriptions with potential therapeutic efficacy for insomnia were predicted and validated using network pharmacology methods.Results:1.415 prescriptions with the efficacy of treating insomnia in the Dictionary of Chinese Medical Formulas were screened,and the four qi,five tastes,the attributive meridians and the efficacy of all drugs in the prescriptions were assigned and calculated,and the four qi database,the five tastes database,the attributive meridians database and the efficacy database of 415 prescriptions were constructed respectively.2.Five standard prescription databases were established for different TCM symptoms,namely,Gentian Diarrhea Liver Soup,Huang Lian Warm Gall Bladder Soup,Gui Spleen Soup,Liu Wei Di Huang Wan combined with Jiaotai Wan,and An Xin Ding Zhi Wan combined with Sour Jujube Ren Tang,and the similarity calculation was done between these five standard prescription databases and 415 prescription databases for insomnia to obtain five calculation models of analogous formulas for insomnia.3.The database of analogous formulas for insomnia medical record was established and the thresholds of analogous formulas for insomnia models were revised.The results showed that the prescriptions with similarity between[0.63,0.86)and Gentian-Diarrhea Liver Tang were the analogous formulas with certain correlation with Gentian-Diarrhea Liver Tang,and the prescriptions with similarity between[0.86,1]were the analogous formulas with strong correlation;the prescriptions with similarity between[0.69,0.89)and Huanglian-Wenchuang were the analogous formulas with certain correlation with Huanglian-Wenchuang,and the prescriptions with similarity between[0.89,1]were the analogous formulas with strong correlation;The formulas with similarity between[0.83,0.90)were analogous formulas with certain correlation with Gui Shen Tang,and those with similarity between[0.90,1] were analogous formulas with strong correlation;the formulas with similarity between[0.62,0.90)were analogous formulas with certain correlation with Liu Wei Di Huang Wan and Jiaotai Wan,and those with similarity between[0.90,1]were analogous formulas with strong correlation;The formulas with similarity between[0.76,0.90)were those with certain correlation with An Shen Ding Zhi Wan combined with Sour Date Ren Tang,and those with similarity between[0.90,1]were those with strong correlation.4.A database of 95 sutra prescriptions from the Treatise on Typhoid was established.The model was used to predict that Gui Zhi Xin Jia Tang belongs to the analogous formulas with strong correlation with Guei Quan Tang for insomnia and Baicalin plus Panaxia and Ginger Tang belongs to the analogous formulas with strong correlation with Huang Lian and Wen Gall Bladder Tang for insomnia in the sutra formula database.Network pharmacology was used to verify that both formulas have the function of treating insomnia.Conclusion:1.In the study of TCM disease and evidence-based analogous formulas,the disease is used as the outline to distinguish different evidence types for research,which can improve the relevance of the model,improve the success rate of modeling,and lay the foundation for the validation and application of the model.2.Different threshold ranges are determined for different evidence models,and the higher the threshold value,the higher the correlation between the formula and the standard formula of this evidence.Using the threshold range of strong correlation can make the model run more stable.3.The computational model of insomnia-like formula predicted that the classic formula Gui Zhi Xin Jia Tang and Huang Qin plus Ginger and Pan Xia Tang from the Treatise on Typhoid had potential efficacy in treating insomnia,and the results of the network pharmacology study further validated this prediction.4.The computational model of analogous formulas for insomnia constructed in this study,guided by TCM theory and using the method of isomorphic feature similarity calculation,is empirically proven to be robust and can be used as a quantitative tool for studying,mining and developing analogous formulas for insomnia,providing methodological reference for modern research of disease-based analogous formulas. |
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