The Research Of Data Mining And Network Pharmacological Mechanism Of Qi-Huang Scholar Wang Xiaoyun In The Treatment Of PCOS

ObjectiveThis is a study of the medical records of Qi Huang scholar Wang Xiaoyun.It collates records on polycystic ovary syndrome(PCOS)treatment,structures information for data mining,and includes interviews the expert regarding the data mining results.It also includes a summary of Qi Huang Wang Xiaoyun’s academic thoughts and experience in treating PCOS,plus a core formula.Through the network pharmacology,the core formula is analyzed by the network of genes,proteins and pathways.This study provides scientific basis for further research into Wang Xiaoyun.Methods1.The medical records of Professor Wang Xiaoyun,a Qi Huang scholar,were collected through Guangdong Hospital of Traditional Chinese Medicine’s Hospital Information System(HIS).The records collected concern PCOS treatment,and are dated between January 2010 and March 2020.The study adopts the 2011 Chinese PCOS diagnostic criteria,and the medical records were collected based on inclusion and exclusion criteria.2.The data is input into the traditional Chinese inheritance auxiliary platform.The core formula for the therapeutic drugs has been mined and arranged with association rules,entropy clustering and other data mining methods,and the core formula has been determined through expert interviews.3.Use the Dis Ge NET database to find PCOS disease gene data.Log into the Dis Ge NET homepage(https://www.disgenet.org/),and click the “search”button at the top of the page to enter the search interface;Select the“diseases” button,and input “Polycystic Ovary Syndrome;CUI:C0032460:”to search;click the “Summery of Gene-Diseases Association” button;select the “Add/Remove Filter” button and set “Score>0.3” to screen for genes with high correlations.4.Use the TCMSPW database to construct traditional Chinese medicine ingredient target data for the core formulae.Log into the TCMSPW homepage(https://tcmspw.com/index.php),and click the “software” button at the top of the page,select TCMSP,and enter “CHEN PI” to search;set OB>0.3,DL>0.18.Perform a second search to obtain the medicinal ingredients for CHEN PI,which can be downloaded page-by-page,sorted and saved in an Excel table.Then input FU LIN,FA BAN XIA and CHUAN XIONG to obtain the four traditional Chinese medicine ingredients for the core formula.Enter “CHEN PI” again to search for all the targets of CHEN PI.Download them page-by-page,and save the to an Excel table.According to the Chinese medicine ingredients retrieved above,screen out the potential targets.Do this for FU LIN,FA BAN XIA and CHUAN XIONG.Combining the four drugs,screen out the targets of the core formula.5.Use the Uni Prot database to transform the target of the core formula into genes.Log into the Uni Prot homepage(https://www.uniprot.org/).Enter the Chinese medicine targets of the core formulas one-by-one directly into the homepage search interface,and obtain the gene names that correspond to the Chinese medicine targets.6.Use the Venn diagram to obtain the intersection genes of the core formula and PCOS.Log into https://bioinfogp.cnb.csic.es/tools/venny/ to construct a Venn diagram of the core formula’s 148 genes and PCOS’s 145 genes.7.Use the STRING database to analyze the protein-protein intersection gene’ s interaction network.Log into the STRING homepage(https://string-db.org/cgi/input.pl).Select “Multiple proteins” and enter the intersection genes obtained from the Venn diagram into the “List Of Names:” box.Then select “Homo sapiens”,“Continue” to get the relevant results.8.Use the DAVID database to analyze the intersection GO enrichment.Log into the DAVID homepage(https://string-db.org/cgi/input.pl)and select“start analysis”.Input the intersection genes obtained from the Venn diagram into the “ Upload Gene List ” box under “ upload ”.Select“Multi-List File”;select “OFFICIAL GENESYMBOL” in “Select Identifier”;Finally,select “Gene List” in “List Type”.Then in the “List” interface,selected the species “Homo sapiens”,and finally select “Click Functional Annotation Chart”.Get the analysis results,download the relevant results,and organize them into an Excel table.9.Use the KEGG database to analyze the pathway.Log into the KEGG homepage(https://www.kegg.jp/)and select “ KEGG Database ”-“ KEGG mapping”-“KEGG mapper”-“Search & Color Pathway”.A search box will appear.Enter the Uni Prot number for the intersection genes line-by-line in the search box.Results1.A total of 67,975 medical records from the Qi Huang scholar Wang Xiaoyu were found through the HIS from January 2010 to March 2020.The medical records were reviewed manually,and a total of 1,498 were included.2.A total of 266 traditional Chinese medicines were involved in 1,498 medical records.The use of the four properties of the medicine were as follows: freeze medicine: 4,024 times;warm medicine: 3,725 times;flat medicine: 2,325 times;cold medicine: 652 times;hot medicine: 245 times.The use the five medicine flavors were as follows: bitter medicine: 6,399 times,sweet medicine: 5,925 times,pungent medicine: 4,256 times,sour medicine: 878 times,salty medicine: 314 times.Medication use: liver meridian: 6,299 times;spleen meridian: 4,834 times;kidney meridian: 3,735times;heart meridian: 3,147 times;lung meridian: 3,146 times;gallbladder meridian: 1,017 times;large intestine meridian: 785 times;small intestine meridian: 743 times;bladder meridian: 696 times.3.Professor Wang Xiaoyun treated over 150 cases of polycystic ovary syndrome with 26 drugs.There were three main types of medicine used:medicines for resolving phlegm and dampness,such as poria,tangerine peel,atractylodes,and pinellia;medicines for promoting qi and removing blood stasis,such as chuanxiong,angelica sinensis,red peony root,moutan peel,cyperus rot,and turmeric;kidney tonic medicine,such as ligustrum lucidum,rehmannia glutinosa,cclipta prostrata,cinnamon and dipsacus.Phlegm-resolving and damp-removing drugs were the most common.4.We found A total of 32 drug pairs based on the association rules(frequencies greater than 100).5.Combining the frequency of drug use,high-frequency drug pairs,and interviews with Wan Xiaoyun,the core formula was determined: chen pi-chuan xiong-fu lin-fa ban xia.6.988 genes related to PCOS were obtained through the DisGeNET database,and 145 genes with high correlation were obtained after screening.7.Through the TCMSPW database,we obtained a total of 24 active ingredients of Poria cocos and 121 targets;63 active ingredients of tangerine peel and 479 targets;189 active ingredients of ligusticum chuanxiong and 1,356 targets;and 116 active ingredients of pinellia ternata and 1302 target points.We set OB ≥ 0.3 and DL≥ 0.18,and obtained a total of 15 Poria cocos active ingredients and 25 target points;6 tangerine peel active ingredients and 69 target points;7 chuanxiong active ingredients and 29 target points;13 Pinellia ternata active ingredients and 87 target points were obtained.A total of 148 effective targets were screened.The Uni Prot database was used to convert the 148 effective targets into 148 genes.8.The 148 core formula genes were intersected with 145 PCOS genes,and 5 overlapping genes were obtained from the Venn diagram: BCL2,BAX,AKR1C1,CYP19A1,and CCNB1.9.Five genes were input into the STRING database,and the proteins expressed by BAX,BCL2 and CCNB1 with the highest interaction intensity were obtained through the PPI network.These three genes were each related to cell apoptosis.10.The DAVID database was used for GO enrichment analysis of 5 intersection genes,and 48 biological processes were obtained,including cell apoptosis,follicular development and cell homeostasis.Eighteen cell components were obtained,including cell membrane,cytoplasm and mitochondria.Four molecular functions were obtained,including BH3 binding domain and channel activation after enrichment.11.The 5 intersection genes’ pathways were analyzed with KEGG.73 pathways were obtained and 25 that may be related to PCOS were screened out.These were P53 signaling pathway,neurotrophin signaling pathway,steroid hormone biosynthesis,cell apoptosis,multicellular apoptosis,endocrine resistance,PI3K-Akt signal transduction pathway,cell cycle,cell aging,ovarian steroid production,progesterone-mediated oocyte maturation,estrogen signal transduction pathway,oocyte meiosis and metabolic pathway.The numbers of targets involved were 3,2,2,2,2,1,1,1,1,1,1,1,1,1,1,respectively.The most relevant pathway was the P53 pathway regulated by BAX/Bcl-2.Conclusion1.Professor Wang Xiaoyun,a Qi Huang scholar,believes that the cause of PCOS is complicated.Kidney deficiencies are the primary culprit,and emotional disorders also play an important role.Whether caused by a kidney deficiency or an emotional disorder,it eventually leads to obstruction of phlegm and/or blood stasis.This may be one of the key pathogeneses of PCOS.2.Professor Wang Xiaoyun understands the main contradictions based on syndrome differentiation.Her prescriptions are simplistic,and the medications are light and concise.In treating PCOS,attention should be paid to regulating the kidney yin and yang in combination with the menstrual cycle.Moreover,treatment consisting of removing phlegm and blood stasis should complete a full cycle.The commonly used prescription for removing phlegm and blood stasis is phlegm and blood stasis siwu decoction.Attention should be paid to psychological treatment,as well as regulating interest and exercise.3.The core formula treats PCOS through multiple genes and multiple targets,and it likely treats PCOS through intervention via the apoptosis P53 pathway.