Professor Li Zhihong's Research On Medication Rules And Core Prescription Mechanism For Low-grade Gastric Intraepithelial Neoplasia

Objective:Through mining and analyzing the clinical prescription data of Professor Li Zhihong's treatment of low grade gastric intraepithelial neoplasia,combing and summarizing Professor Li Zhihong's clinical experience in treating spleen and stomach diseases,we hoped to find a more reasonable and effective Chinese medicine treatment of low grade gastric intraepithelial neoplasia.Then we further analyzed the drug action mechanism of Professor Li Zhihong's core prescription for the treatment of low grade gastric intraepithelial neoplasia with the help of network pharmacology methods,and provided a certain reference for the clinical application of traditional Chinese medicine in the treatment of low grade gastric intraepithelial neoplasia.Methods:Using frequency statistics,correlation analysis,attribute and efficacy analysis of Chinese medicine,cluster analysis(Lance distance method was used in clustering method and longest distance method was used in distance type)and complex network analysis in Ancient and Modern Medical Cases Cloud Platform software for Professor Li Zhihong's clinical prescriptions in the treatment of low grade gastric intraepithelial neoplasia,we summarized Professor Li Zhihong's clinical medication rule,experience characteristics and so on in the treatment of low grade gastric intraepithelial neoplasia.Comprehensive application of traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP,http://tcmspw.com/tcmsp.php)and traditional Chinese medicine integrative database(TCMID,http://www.megabionet.org/tcmid/)screen active ingredients and corresponding targets of drugs of core prescription.Gene Expression Omnibus(GEO)database was used to screen the relevant targets of low grade gastric intraepithelial neoplasia.Then we determined the intersection genes between the target of the drug and the disease therapeutic targets,and further built the "drug-ingredients-targets-disease" network of core prescription.Next,we used search tool for recurring instances of neighbouring genes(STRING,https://www.string-db.org/)to build a Protein-to-protein interaction(PPI)network and used the Database for Annotation Visualization and Integrated Discovery(DAVID,https://david.ncifcrf.gov/)for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Results:There were 106 prescriptions entered into the system,including 123 kinds of Chinese medicine.A total of 24 kinds of medicines were used more than 20 times.Among them,the top 10 medicines with the highest frequency of use are Pseudostellariae Radix(95 times),Hedyotis Diffusae Herba(95 times),Caulis Perillae(84 times),Coicis Semen(82 times),Taraxaci Herba(65 times),Radix Bupleuri(63 times),Lilii Bulbus(63 times),Curcumae Rhizoma(57 times),Sepiae Endoconcha(54 times),Forsythiae Fructus(54 times).The most frequently used effective and strong-related drug combinations in the Chinese medicine data were Pseudostellariae Radix-Hedyotis Difusae Herba(92),Hedyotis Diffusae Herba-Caulis Perillae(92),Pseudostellariae Radix-Coicis Semen(79),Hedyotis Diffusae Herba-Coicis Semen(79),Pseudostellariae Radix-Caulis Perillae(80),Caulis Perillae-Coicis Semen(77),Pseudostellariae Radix-Lilii Bulbus(62),Caulis Perillae-Radix Bupleuri(61),etc.The statistics of drug properties and efficacy showed that the character of medicine was mainly cold and sweet,and the channel tropisms were mainly based on spleen,and the efficacy was mainly based on clearing away heat and toxic material.Cluster analysis showed that the medicines can be divided into 8 categories:the medicine of first category was Poria Cocos(Schw.)Wolf.,Citrus Reticulata,Artemisia Annua L.,Curcumae Radix;the medicine of second category was Panax Notoginseng(Burk.)F.H.Chen Ex C.Chow,Citri Fructus,Aurantii Fructus;the medicine of third category was Pine Pollen;the medicine of fourth category was Duchesnea indica(Andr.)Focke,Pollen Typhae;the medicine of fifth category was Semen Pharbitidis;the medicine of sixth category was Dendrobii Caulis,Curcumae Rhizoma,Lilii Bulbus,Linderae Radix;the medicine of seventh category was Sepiae Endoconcha,Fritillariae Thunbrgii Bulbus;the medicine of eighth category was Taraxaci Herba,Forsythiae Fructus,Radix Bupleuri,Pseudostellariae Radix,Hedyotis Diffusae Herba,Caulis Perillae,Coicis Semen.Complex network analysis showed that the core prescription was Shenbai Granule.After network pharmacological analysis of the core prescription Shenbai Granule,we got that Shenbai Granule contained 43 constituents with corresponding 334 targets and there 2472 disease therapeutic targets were screened.Then 50 common targets were selected through the Venn diagram and 23 GO functional items and 10 KEGG signaling pathways were obtained through enrichment analysis.Conclusion:Professor Li believes that the overall pathogenesis of low grade gastric intraepithelial neoplasia is based on deficiency in origin and excess in superficiality,and"deficiency" mainly lies in the deficiency of both Qi and Yin;"exactness" mainly lies in stagnation of Qi,stagnation of heat,blood stasis,toxin stasis,etc.Professor Li's medication is mostly mild and gentle,to restore the physiological functions of the spleen and stomach.The core prescription Shenbai Granule was created based on Professor Li's understanding of the pathogenesis of low grade gastric intraepithelial neoplasia.Its main effects are regulating Qi and promoting blood circulation,replenishing Qi and nourishing Yin,clearing away heat and toxic material.At the same time,Shenbai Granule mainly participates in biological processes such as oxidation-reduction process,cell proliferation,response to oxidative stress,angiogenesis,and biological pathways such as Pathways in cancer,Neuroactive ligand-receptor interaction,Arachidonic acid metabolism and Hypoxia inducible factor 1(HIF-1)signaling pathway to play a therapeutic role.