Research On The Medication Rule And Mechanism Of Hu Shunjin In The Treatment Of Non-dialysis CKD Stage 3-5 Based On Data Mining And Network Pharmacology

Study 1: To investigate the regularity of Hu Shunjin in the treatment of non-dialysis CKD stage 3-5 based on data mining.Objective: To sort out the medical records of Director Hu Shunjin in the treatment of nondialysis CKD3-5 stage,and explore the medication regularity of Hu Shunjin in the treatment of non-dialysis CKD3-5 stage using data mining technology.Methods: The medical records of non-dialysis patients with CKD stage 3-5 who were diagnosed and treated by Director Hu Shunjin from December 2020 to December 2022 were screened and entered into the Traditional Chinese Medicine Inheritance Support Platform(V2.5).The general information,syndrome distribution,drug frequency and taste meridians of the medical records were statistically analyzed using this platform.The statistical results were collated and plotted with the help of Excel software,and the drugs were further analyzed for association rules to obtain the core prescription.The potential new prescriptions were excavated through cluster analysis.Result: 1.In this study,163 cases were collected,including 91 males and 72 females.The age distribution was mainly concentrated in 50-59 years old,accounting for 38.04%.CKD stage was dominated by G3 stage,accounting for 49.69%.A total of 602 prescriptions were involved in the included cases.The distribution of syndromes was mainly damp-heat and blood stasis syndrome,followed by spleen and kidney qi deficiency and water dampness and blood stasis syndrome,accounting for 26.74% and 19.77% respectively.The two syndromes with the largest proportion above were selected for further drug use rule analysis,and the number of other syndromes was small.In order to prevent deviation,the mining analysis was not conducted temporarily.2.A total of 161 prescriptions were collected for dampness-heat and blood stasis syndrome,involving 93 herbs and 22 drugs used ≥ 30 times,and the top ten drugs were rhubarb,aurantium aurantium,phellodendron amurense,Smilax glabra,Achyranthes bidentata,peach kernel,Zhuru,hemp kernel,June snow,and calcined oyster.The drug efficacy is divided into 17 categories,mainly heat-clearing drugs,blood-activating and stasis-dissipating drugs and purgative drugs,and the drugs are cold and bitter in taste,sweet,and mostly return to the liver meridian.Twenty-six groups of commonly used drug combinations were obtained by association rule analysis,including 17 groups of two-drug combinations and 9 groups of three-drug combinations,and 17 association rules were obtained,and the core prescriptions were selected as Phellodendron amurense,Smilax glabra,Rheum officinale,Citrus aurantium,Achyranthes bidentata,and Taoren.Cluster analysis resulted in 14 potential core drug combinations and 7 candidate novel formulations.3.A total of 119 prescriptions were collected for spleen and kidney qi deficiency and water dampness and blood stasis syndrome,involving 82 herbs and 23 herbs used ≥ 20 times,and the top ten drugs were Atractylodes macrocephala Koidz,Poria cocos,Rheum officinale,Citrus aurantium,Codonopsis pilosula,Achyranthes bidentata,Yam,Hemp seed,Coix seed,and Taoren kernel.The drug efficacy is divided into 16 categories,mainly tonic drugs,followed by blood-activating and stasis-dissipating drugs,water and dampness drugs and purgative drugs,etc.The drugs are mainly flat and sweet in nature and return to the spleen meridian.After association rule analysis,43 groups of commonly used drug combinations were obtained,including 22 groups of two-drug combinations,17 groups of three-drug combinations,4 groups of four-drug combinations,and 39 association rules,and the core prescriptions were selected as Codonopsis pilosula,Atractylodes macrocephala,Poria cocos,Yam,Rheum officinale,Citrus aurantium,and Achyranthes bidentata.Cluster analysis resulted in 12 potential core drug combinations and 6 candidate novel formulations.Study 2: To explore the potential mechanisms of action of core drugs in CKD treatment based on network pharmacology.Objective: To explore the potential mechanism of core drugs in the treatment of CKD based on network pharmacology for dampness-heat and blood stasis syndrome,spleenkidney qi deficiency and water-dampness and blood stasis syndrome.Method: CKD related targets were obtained in the Dis Ge NET database,DRUGBANK database,TTD database,and Gene Cards database,respectively.Core active pharmaceutical ingredients and target proteins were searched with the aid of TCMSP database and literature.With the help of Wayne diagram to obtain the common targets of core drugs and CKD,Cytoscape 3.9.1 software was used to construct the network diagram of "core drugs-active ingredients-common targets-CKD" and select the key active ingredients.Two sets of common target PPI maps were obtained using STRING 11.5 database,and core targets were selected with the help of Cyto NCA plugin.GO function and KEGG conduction pathway enrichment were performed for the two groups of common targets using the Metascape database,respectively.Result: 1.The number of CKD-related targets obtained in the Dis Ge NET database,DRUGBANK database,TTD database,and Gene Cards database was 1074,73,6,and 14571,respectively,and 1377 CKD-related targets were obtained after standardization and screening and weight removal.2.The core drugs of dampness-heat and blood stasis syndrome were searched by TCMSP database,and the number of active components was 37 for Phellodendron amurense,15 for Smilax glabra,16 for Rheum officinale,5 for Citrus aurantium,4 for Achyranthes bidentata,and 23 for Taoren.Obtaining 119 Common Targets of Core DrugCKD with Venny Diagram,and Using Cytoscape 3.9.1 to construct the network diagram of "core drug-active components-common target-CKD",and screen out the main active components with the highest degree value as quercetin,beta-sitosterol and naringin,etc.Obtain the PPI diagram of common targets through STRING database,and screen out 19 core targets including IL6,AKT1,TNF,VEGFA,and IL1 B with the help of Cyto NCA plug-in.GO enrichment shows that biological processes mainly involve reactions to hormones and inorganic substances;Membrane raft and membrane micro-area are the main enrichment items of cell components.Among the molecular function items,cytokine activity and transcription factor binding are significantly enriched.The enrichment of KEGG pathway found that genes were mainly concentrated in cancer signaling pathway,lipid and atherosclerosis,PI3 K Akt signaling pathway,etc.3.Through TCMSP database,we searched the core drugs of spleen and kidney qi deficiency combined with water dampness and blood stasis syndrome,and obtained 21 active components of Codonopsis pilosula,7 Atractylodes macrocephala,15 Poria cocos,and 16 yam,combined with 16 active components of rhubarb,5 Citrus aurantium,and 4 Achyranthes bidentata that had been searched,a total of 216 targets were selected after standardization and weight removal.Obtaining 114 Common Targets of Core Drug-CKD with Venny Diagram,and Using Cytoscape 3.9.1 to construct the network diagram of "core drug-active components-common target-CKD",and screen out the main active components with the highest degree value as quercetin,β-sitosterol and luteolin,etc.Obtain the PPI diagram of common targets through STRING database,and screen out 17 core targets including AKT1,IL6,TNF,VEGFA,and TP53 with the help of Cyto NCA plug-in.GO enrichment shows that biological processes mainly involve reactions to peptides and hormones;Membrane raft and membrane micro-area are the main enrichment items of cell components.Among the molecular function items,cytokine activity and cytokine receptor binding are significantly enriched.The enrichment of KEGG pathway found that genes were mainly concentrated in cancer signaling pathway,PI3 K Akt signaling pathway,lipid and atherosclerosis.Conclusion: 1.Director Hu Shunjin treated non-dialysis CKD3-5 stage damp-heat and blood stasis syndrome by clearing away heat and dampness,removing blood stasis and removing turbidity.The drugs used were mainly heat-clearing drugs,purgative drugs and bloodactivating drugs;Spleen and kidney qi deficiency combined with water dampness and blood stasis syndrome is treated by invigorating the spleen and infiltrating dampness,supplementing qi and kidney,removing blood stasis and removing turbidity.It is usually treated with drugs for tonifying deficiency,activating blood circulation and removing blood stasis,promoting water and infiltrating dampness,and purgative drugs.Its clinical medication reflects the characteristics of "focusing on the treatment of symptoms and taking into account the deficiency".2.In this study,the core drugs of high frequency syndrome of damp-heat combined with blood stasis syndrome and spleen and kidney qi deficiency combined with water dampness and blood stasis syndrome can play a role in the treatment of CKD through multiple active components and multi-target action on multiple signal pathways,and interfere with the development of CKD disease.