Professor Li Xiaojuan's Medication Rules And Network Pharmacology Research In The Treatment Of Thyroid Nodule

Purpose:1.By using data mining method,the author analyzed Professor Li Xiaojuan’s experience in treating thyroid nodule and explored her treatment philosophy,so as to inherit the academic thoughts of famous old Chinese medicine practitioners.2.Based on network pharmacology,explore the mechanism of core drugs in the treatment of this disease,and provide reference for clinical diagnosis and treatment.Material and method:1.From September 2020 to October 2022,the medical records of thyroid nodule patients treated by Professor Li Xiaojuan personally in the Department of Endocrinology and Rehabilitation,Affiliated Hospital of Liaoning University of Traditional Chinese Medicine were collected.The data were standardized cleaned according to the NADation standard,and a database was established using WPS Officic Excel.Basic information of patients was analyzed and drug frequency and efficacy were counted.Cluster analysis and association analysis of high-frequency drugs were conducted using SPSS software,and visualization processing was carried out on Cytoscape3.7.1 to screen out core drugs,and to summarize the medication rules and academic thoughts of Professor Li Xiaojuan in the treatment of thyroid nodule.2.The active ingredients and action targets of core drugs were screened out through TCMSP database and BATMAN-TCM database.Thyroid nodule related targets were collected from OMIM database,Genecards database and DisGeNET database.The intersecting targets were selected and imported into String database to construct target protein interaction(PPI)network.To construct a network graph of "medicine-active-core target" by Cytoscape 3.7.1,and to analyze its GO and KEGG enrichment by DAVID database,to further explore the mechanism of core drugs in treating thyroid nodule.Results:1.Gender and age analysis: Among the 131 patients,20 were male,accounting for15.27%;There were 111 females,accounting for 84.73%.The prevalence rate of females was 5.5 times that of males.The age group was mainly from 40 to 59 years old,accounting for 64.88% of the total.2.Drug frequency analysis: A total of 203 cases of prescriptions for initial diagnosis and rediagnosis were counted,with a total drug frequency of 3063 times,involving 154 doses.There were 8 drugs with more than 120 times,a total of 1250 times,accounting for40.81% of the total drugs,which were Zedoary Turmeric,Rhizoma Sparganii,Radix Bupleuri,Peach kernel,Leech,Cyperi Rhizoma,Fructus Aurantii,Rhubarb.There were 32 kinds of drugs used more than 20 times,which accounted for 2454 times in total,accounting for 80.12% of the total drugs.They were the commonly used drugs in the treatment of TN by Professor Li Xiaojuan.3.Drug category analysis: 154 traditional Chinese medicines were classified into 17 categories.The use frequency of promoting blood circulation and removing blood stasis was the highest,725 times,accounting for 23.67%;Qi regulating drugs,phlegm relieving cough and antiasthmatic drugs,heat clearing drugs followed,and the remaining use frequency was less than 10%,a total of 13 categories.4.Cluster analysis: A total of 6 cluster combinations were obtained.Combination 1:Zedoary Turmeric,Rhizoma Sparganii,Radix Bupleuri,Peach kernel,Leech,Cyperi Rhizoma,Fructus Aurantii,Rhubarb,Seaweed,Kunbu,Xanthapodium;Combination 2:Litchi seed,Citri Reticulatae Semen,Cassis ushroom,Inulae Flos,Madder;Combination 3:platycodon grandiflorum,licorice scrophulariae,Forsythia and Hedyoglossia;Combination4:Prunella,Fritillary thunberg and oyster;Combination 5:Chinaberry seed,corydalis corydalis,Turmeric,Xylem;Combination 6:Pinellia pinellia,Magnolia officinalis,poria cocos,Perilla leaves.5.Association rule analysis: The minimum conditional support was selected as 60.0,and the minimum rule confidence was 95%.When the maximum number of the first terms was set as 1,2,3,respectively,it was found that all the drug combinations contained Zedoary Turmeric,Rhizoma Sparganii,Radix Bupleuri,Peach kernel,Leech,Cyperi Rhizoma,Fructus Aurantii,Rhubarb.And these eight drugs are the core drug prescription of Professor Li Xiaojuan to treat this disease,which is consistent with the results of complex network analysis.6.Network pharmacological analysis: There were 86 active components and 534 related targets in the core drug combination.There were 1007 targets related to thyroid nodule,and 139 targets intersecting with drug targets.PPI network analysis could obtain 128 core targets,and the top 10 targets were MAPK3,MAPK1,JUN,AKT1,TP53,RELA,IL6,TNF,RXRA,and MAPK14.The network diagram of "drug-active ingredient-core target" showed that the main components of TN treated by the core drugs were quercetin,β-sitosterol,kaempferol,luteolin,isorhamnetin and Tibetan acid.7.GO enrichment analysis obtained 907 biological processes(BP),including positive regulation of gene expression,positive regulation of RNA polymerase Ⅱ promoter transcription,negative regulation of apoptosis process,etc.74 cell components(CC),involving extracellular Spaces,chromatin,nuclei,etc.Molecular function(MF)140 items mainly include protein binding,enzyme binding,cytokine activity,etc.8.KEGG pathway analysis showed 171 signaling pathways,among which MAPK signaling pathway,IL-17 signaling pathway,PI3K-Akt signaling pathway and TNF signaling pathway were important pathways for the treatment of thyroid nodules with core drugs.Conclusion:1.Through the data mining study,it was found that Li Shi mainly used drugs to promote blood circulation and remove blood stasis in the treatment of thyroid nodules,and also used drugs to regulate qi,reduce phlegm and clear heat.The core drugs included Zedoary Turmeric,Rhizoma Sparganii,Radix Bupleuri,Peach kernel,Leech,Cyperi Rhizoma,Fructus Aurantii,Rhubarb.2.Through network pharmacological research,it was concluded that quercetin,kaempferol,β-sitosterol,isorhamnetin,kosonic acid,luteolin and other active components of core drugs may act on MAPK3,MAPK1,JUN,AKT1 and other targets.With the participation of IL-17 signaling pathway,MAPK signaling pathway,TNF signaling pathway and PI3K-Akt signaling pathway,it can inhibit inflammation and anti-tumor and achieve the purpose of treating thyroid nodule.