Medication Rules And Network Pharmacology Of Traditional Chinese Medicine For The Treatment Of Theroid Nodules

Objective:This study used data mining technology to analyze the effective outpatient case data of the Department of Endocrinology of the First Affiliated Hospital of Heilongj iang University of Chinese Medicine for the treatment of thyroid nodules,and to derive the medication pattern and core drugs for the treatment of this disease in Chinese medicine.At the same time,the possible mechanisms of action of the core drugs in the treatment of thyroid nodules were investigated to provide a scientific basis for the clinical treatment of thyroid nodules in TCM.Methods:In this study,we collected valid outpatient cases of thyroid nodules patients treated at the Department of Endocrinology of the First Affiliated Hospital of Heilongj iang University of Traditional Chinese Medicine from September 2021 to September 2022,and entered the patients’ basic information,four diagnostic data and herbal prescriptions into EXCEL software to establish a database of patients’ medical record information.The data were statistically analyzed through the data analysis module in the TCM inheritance computing platform(version V3.0),and information on the morbidity characteristics,evidence distribution characteristics,symptom characteristics,frequency of herbal medicine use,four qi and five flavors,drug attribution,and drug pair combinations of thyroid nodules were deeply excavated,and core prescriptions were extracted.A network pharmacology study was conducted for the core formulae derived from the analysis of the TCMSP(V3.0).The active chemical components in the core formula were obtained by searching the TCMSP database and converted into the corresponding target genes using the Uniprot database.Also,targets associated with benign thyroid nodules were collected in the disease gene database.The protein-protein interaction(PPI)network map of coreside-benign thyroid nodules was constructed by STRING database and Cytoscape 3.7.1 software.Ends were analyzed for GO and KEGG pathway enrichment using the Metascape database.Results:1.Basic patient characteristics:(1)Of the 141 cases that met the inclusion criteria,12 8 were female patients and 13 were male patients.(2)Symptoms:from high to low frequency were insomnia,fatigue,impatience and irritability,chest tightness,neck discomfort,excessive sweating,yellow urine,palpitations,distention and fullness of the abdomen and bowels,and constipation.(3)Tongue:The first four tongue images concentrated on the tongue are dark tongue,red tongue,fat tongue,and tongue with teeth marks.The first four signs of tongue coating are:white moss,white greasy moss,thin yellow moss,yellow greasy moss.(4)Symptoms:the frequency distribution of symptoms from high to low was phlegm and stagnation(26.55%),liver and gallbladder heat(18.58%),spleen and kidney yang deficiency(14.16%),qi stagnation and phlegm coagulation(11.50%),and liver fire(9.73%);(5)Treatment:the frequency distribution from high to low was warming the spleen and kidney(30 times),softening and dispersing the knots(25 times),clearing the liver and gallbladder(22 times),and(16 times),and the method of resolving phlegm and eliminating galls(16 times).2.Medication pattern:A total of 141 prescriptions with 120 herbal medicines were included in the study,and the results of statistical analysis were:(1)The top 10 herbal medicines in order were Danshen(13 0 times),Fu Ling(129 times),Licorice(123 times),Semen(117 times),Scutellaria(112 times),Xiao Tong Cao(111 times),Chen Pi(107 times),Xia Ku Cao(100 times),San Ling(97 times)and Curcuma(97 times).(2)medicinal properties:the largest proportion of cold drugs(50.87%);warm drugs were second(3 5.57%);(3)five flavors:bitter drugs had the highest frequency(38.09%);followed by pungent drugs(28.97%).(4)Attribution to meridians:from highest to lowest frequency were spleen meridian(1 5 5 8 times),liver meridian(1 3 24 times),lung meridian(1290 times),stomach meridian(1409 times),heart meridian(847 times),gall bladder meridian(5 6 7 times),kidney meridian(5 42 times),large intestine meridian(3 3 8 times),small intestine meridian(18 7 times),sanjiao meridian(16 5 times),bladder meridian(9 8 times),and pericardium meridian(3 1 times).(5)The meridian clustering analysis yielded six new formula combinations:New formula 1:Gly cyrrhiza glabra,Pori a,Salvia,Semen,Radix Bupl eurum,Scutellaria,Radix Scutellariae,and Plantago.New formula 2:Dan Shen,Xiao Tong Cao,Fu Ling,Hou Pu,San Ling,Qing Pi,Turtle A,Xia Ku Cao.New formula 3:Salvia,Semen,Pori a,Gly cy rrhiza,Scutellaria,Xiaotongcao,Chen Pi,Citrus aurantium.New formula 4:Gly cy rrhiza glabra,Pori a,Radix Aromaticus,Radix Bupleurum,Oyster,Salviae Miltiorrhizae,Rhizoma Polygonatum,Radix et Rhizoma Longan.New formula 5:Qing Pi,Semen,Xia Gu Cao,San Ling,Dan Shen,Curcuma,Chen Pi,Pori a.New formula 6:Sanleng,Zhebei,Qingpi,Hanxi a,Turtle shell,Houpu,Xia Gu Cao Cao,Ze Di.(6)Extracted core formula consisting of Pori a,Salvia,Semen,and Pericarpium.3.Network pharmacological study:(1)A total of 81 effective compounds in the core formula were obtained in this study,and those with high degree values mainly included lignanin,naringenin,Chuan Chenpiin,tanshinone Ⅱa,baicalin and dihydrotanshinolide,which mainly acted on the targets of AKT1,GAPDH,TP53,TNF,VEGFA,IL1B and CASP3.(2)PPI network construction shows that its core targets are AKT1,GAPDH,TP53,TNF,VEGFA,IL1B,CASP3,HIF1A,PTGS2,MMP9,PPARG,FOS,ESR1,PTEN,IL10.(3)GO biological processes are mainly cellular responses to hypoxia,responses to hormones,and responses to inorganic substances;The molecular functions are mainly DNA transcription factor binding,protein kinase binding,kinase binding;the cell composition is mainly secretory granule lumen,transcriptional regulatory complex,vesicle lumen,cytoplasmic vesicle lumen,etc.(4)KEGG enrichment analysis mainly involves cancer pathways,inflammation-related pathways and metabolism-related pathways,and is closely related to AGERAGE signaling pathway,IL-17 signaling pathway,PI3 K-Akt signaling pathway,p5 3 signaling pathway,and TNF signaling pathway.Conclusion:1.In this study,there were more women than men with thyroid nodules,and the age of onset was mostly 36-59 years old,with clinical evidence of phlegm and blood stasis and liver and gallbladder heat.2.The herbs used in this study were mostly cold and warm in nature,with bitter,pungent and sweet flavors,and mainly belonged to the spleen,liver,lung and stomach meridians.These are consistent with the drug properties required for the treatment of phlegm nodules and blood stasis evidence.3.Based on the results of the evidence type analysis,frequency of drug use and drug association rules,the core drugs were extracted:Poria,Salvia,Semen,and Chen Pi and formulated as the core formula for the treatment of benign thyroid nodules.4.Through the network pharmacological study of the core formula,it was found that the active ingredients are mainly naringenin,Chuan Chen Piin,lignanin,tanshinone IIA,baicalin,etc.,which can act on the targets of AKT1,TNF,TP53,VEGFA,GAPDH,IL-1β,CASP3,HIF1A,etc.5.The core formula for the treatment of thyroid nodules may interfere with cancer pathways,inflammatory pathways and metabolism-related pathways,modulate gene targets such as AKT1,TNF,TP53,VEGFA,GAPDH and IL-1β,improve chronic inflammatory response,anti-tumor and modulate immunity,and thus play a role in the treatment of thyroid nodules.