Traditional Chinese Medicine Syndrome Analysis And Medication Rule Of Polycystic Ovary Syndrome Based On Latent Structure Model

Objective: Polycystic Ovary Syndrome is the most common and frequent endocrine disorder and metabolic disorder in women of reproductive age and adolescents worldwide.Traditional Chinese medicine(TCM)treatment can alleviate the symptoms of endocrine disorders in patients at the stage of the disease,reduce the discomfort of patients,and improve the quality of life and physical and mental health of patients.In this study,the modern literature and classical medical cases of prestigious Chinese medicine doctors with polycystic ovary syndrome treated by TCM were collated and analyzed.The common TCM syndromes of polycystic ovary syndrome were explored based on the latent structure model,and summarized and analyzed the medication characteristics and potential mechanisms of action of TCM in the treatment of polycystic ovary syndrome by combining various data mining methods.Methods:1.China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP Chinese Journal Database,China Biomedical Literature Service System,Ancient and Modern Medical Cases Cloud Platform and prestigious Chinese medicine doctors’ experience books were searched.The clinical cases and clinical studies of polycystic ovary syndrome treated with traditional Chinese medicine from the establishment of the database to June 5,2022 were collected.The key information such as symptoms and traditional Chinese medicine was extracted,and the database was classified and standardized.2.The Lantern v5.0 software of the latent structure analysis method was used to construct the latent structure model of the symptoms based on the two-step hidden tree analysis LTM-EAST algorithm,which was combined with the knowledge of TCM.The results were interpreted by the extensive link analysis,and the symptoms or implicit classes that were meaningful and in line with the characteristics of the pathogenesis of TCM were extracted for comprehensive clustering,and the common syndrome of TCM was inferred.3.Combined with the TCM prescription database,after standardized processing,the types,properties,flavors and meridians of TCM were analyzed by frequency analysis and co-occurrence analysis,and the high-frequency drugs used in common TCM syndromes obtained by the latent structure model were analyzed.SPSS Statistics v22.0 and SPSS Modelor v18.0 software were used to perform complex network,association rules and cluster analysis of symptoms and prescription drugs,and to explore the compatibility rules of TCM in the treatment of polycystic ovary syndrome and the distribution characteristics of TCM and symptoms.4.K-means cluster analysis was used to explore the core prescriptions of TCM for the treatment of polycystic ovary syndrome of kidney deficiency and blood stasis type collected in Chapter 3.The chemical components of TCM contained in each core prescription were searched and the targets were screened through TCMSP,ETCM and HERB databases.The disease-related targets were collected through Durg Bank,Gene Cards,NCBIGene,OMIM,Pharm Gkb and TTD databases,and the protein-protein interaction network was constructed by STRING platform and the core targets were screened.Fun Rich software was used to enrich the expression sites of its core class,R software was used for KEGG enrichment pathway analysis,Cytoscape software was used to construct the visualization map of "traditional Chinese medicine-active ingredient-core target-pathway" network,Autodock software was used for molecular docking,and Pymol software was used for visualization.Results:1.A total of 849 articles were included,954 medical cases,a total of 1237 records,involving 288 syndrome types.The syndrome types with frequency ≥5% were kidney deficiency and phlegm dampness syndrome(7.84%),kidney deficiency and blood stasis syndrome(6.71%),kidney deficiency and liver stagnation syndrome(5.98%),kidney deficiency and phlegm stasis syndrome(5.34%),etc.There were 67 symptoms with frequency ≥5%,including late menstruation(59.50%),infertility(56.27%),physical obesity(54.73%)and low menstrual volume(52.47%),etc.Through the analysis of the latent structure,23 hidden variables were obtained,and according to the relevant knowledge of TCM,9 common syndrome syndromes were obtained,including kidney deficiency and phlegm dampness syndrome,kidney deficiency and blood stasis syndrome,spleen and kidney Yang deficiency syndrome,spleen deficiency and phlegm dampness syndrome,liver stagnation and spleen deficiency syndrome,kidney Yang deficiency syndrome,kidney deficiency and liver depression syndrome,phlegm and blood stasis syndrome and qi and blood deficiency syndrome.2.A total of 1495 TCM prescriptions,377 Chinese herbs,67 symptoms with frequency ≥5% were included.There were 50 herbs with frequency ≥100,including Angelica sinensis,Poria coporia,cuscutazi,etc.The main types of drugs were tonifying drugs,promoting blood circulation and removing blood stasis drugs,and regulating qi drugs.The properties of the drugs were mainly warm,flat and cold,the tastes of the drugs were mainly sweet,spicy and bitter,and the meridians were mainly kidney meridians,spleen meridians and liver meridians.The results of complex network analysis showed that there were strong links between late menstruation,obesity,low menstrual volume,infertility,dark red menstrual color,menstrual blood clots,hirsutism,acne and other symptoms.Through the analysis of complex network and association rules of high-frequency Chinese herbs,it was found that there were strong links between Angelica sinensis,Poria cocos,Cuscuta semen,Xiangfu,Chuangxiong,Rehmannia,Tangerine peel,Radix paeoniae alba,Atractylodes atractylodes,and so on.In the PCOS common medication group,there were Poria cocos and Tangerine peel.Angelica-Chuanxiong,Cuscutae;Poria-Atractylodes rhizome,Tangerine peel;Angelica sinensis-Chuanxiong Rhizoma;Angelica-Chuanxiong,Xiangfu,etc.Finally,four cluster prescriptions were obtained by cluster analysis of high-frequency core traditional Chinese medicine.The first category was:(1)peach kernel,safflower,red peony,Angelica sinensis,Chuangxiong;(2)Motherwort,Zeeland,Sichuan Achyranthes;(3)Salvia miltiorrhiza and Jixueteng.The second class:(1)Epimedium and Euphorbia alba;(2)dodder,Wolfberry,yam,cornus officinalis,Rehmannia;(3)Dipsacus and Ligustri lucidi.The third category:(1)Radix paeoniae alba,Radix bupleurum;(2)Raw Rehmannia and moutan.The fourth category:(1)Codonopsis,Astragalus,Atractylodes;(2)Tangerine peel,Pinellia pinellia,Atractylodes atractylodes atractylodes atractylodes,Poria cocos.3.A total of 351 prescriptions of TCM for the treatment of polycystic ovary syndrome of kidney deficiency and blood stasis type were included in Chapter 3,and five core categories were obtained by K-means clustering.The core prescription 1 consisted of 6Chinese herbs(Semen cuscutae,Angelica sinensis,Lycium barbarum,Poria cocos,Rhizoma fragrans and Atractylodes atractylodes),120 chemical components and 1778 targets.The core prescription 2 included 6 Chinese herbs,Angelica sinensis,Dodder semen,Xiangfu,Poria cocos,Licorice and Chuangxiong,with 189 chemical components and 3268 targets.The core prescription 3 included 6 Chinese herbs,including dodder semen,Angelica sinensis,processed Rehmanniae,safflower,peach kernel and Chuangxiong,90 chemical components and 1288 targets.The core prescription 4 included 6 Chinese herbs,including Angelica sinensis,Cuscuta semen,Rehmannia rehmanniae,saponiae saponiae,Poria cocos and Bupleurum,92 chemical components and 2086 targets.The core prescription 5 included6 Chinese herbs,including amethyseite,dodder semen,Epimedium,Angelica sinensis,Xiangfu and Salvia miltiorrhiza,142 chemical components and 2066 targets.The core targets related to the five core prescriptions were all involved in ACTB,ALB,AKT1,INS,TP53,JUN,VEGFA,ESR1,MYC,EGFR and CASP3,and most of the potential targets of the five core prescriptions in the treatment of polycystic ovary syndrome were highly expressed in endometrium and small intestine.KEGG pathways were mainly enriched in inflammation,glucose metabolism and cancer related pathways,among which the most involved pathways were mostly related to inflammation and glucose metabolism.4.The main active ingredients of the five core prescriptions were luteolin,ononetin,β-sitosterol,kaonafol,β-carotene,quercetin,ingenin,fisetin,and baicalein,etc.The main targets were MAPK3,MYC,PTGS2,HSP90AA1,STAT3,ALB,and ACTB.The main pathways included MAPK,HIF-1,AGE-RAGE,Thyroid hormone and other signaling pathways.The absolute value of molecular docking results between the main targets and their main active ingredients of the five core classes was greater than 5.0Kcal/mol,which indicated that the docking results were good.Conclusion:1.There were 9 clinical common TCM syndromes of polycystic ovary syndrome,including kidney deficiency and phlegm dampness syndrome,kidney deficiency and blood stasis syndrome,spleen and kidney Yang deficiency syndrome,spleen deficiency and phlegm dampness syndrome,liver stagnation and spleen deficiency syndrome,kidney Yang deficiency syndrome,kidney deficiency and liver depression syndrome,phlegm and blood stasis syndrome and qi and blood deficiency syndrome.2.TCM drugs are mainly used for tonifying deficiency,with warm nature,sweet taste,regulating the liver,spleen and kidney meridians.Combined with a variety of data mining methods,it was concluded that polycystic ovary syndrome was mainly characterized by late menstruation,obesity,low menstrual volume,infertility,dark red menstrual color,menstrual blood clots,hypertrichosis,acne and other deficiency and excess mixed symptoms,involving "phlegm dampness","blood stasis" and "qi stagnation" syndrome elements,The relationship between drugs and diseases is generally in line with the therapeutic thinking that the clinical treatment of TCM focuses on warming the kidney,strengthening the spleen and soothing the liver,and also on removing blood stasis,regulating qi,drying dampness and eliminating phlegm.3.TCM in the treatment of polycystic ovary syndrome of kidney deficiency and blood stasis may play its therapeutic effect by improving insulin resistance,anti-inflammation,and promoting follicle development.