| Objective1.Through data mining technology,this paper probes into Professor Fan Guanjie’s medication rules and core compatibility prescriptions in the treatment of gouty arthritis,and combines clinical induction to form Fan’s gout decoction and summarizes tutor’s academic thoughts.2.To explore the main active ingredients,targets and signaling pathways of Fan’s gout decoction in the treatment of gouty arthritis using network pharmacology and molecular docking technology,predict the potential mechanism of action of Fan’s gout decoction in the treatment of gouty arthritis,and provide theoretical basis for subsequent clinical research.3.By exploring the efficacy and safety of Fan’s gout decoction in the treatment of acute gouty arthritis(damp-heat syndrome),it provides a safe and effective new idea and method for the clinical treatment of gout.Methods1.Clinical retrospective study:To explore the medication rules of Professor Fan Guanjie in the treatment of gouty arthritis based on data mining.A retrospective study was conducted to collect 693 patients with gouty arthritis who met the inclusion criteria and were treated in the outpatient department of Professor Fan Guanjie in Guangdong Provincial Hospital of Traditional Chinese Medicine from 2011 to 2020.The medical records and prescription drugs were uniformly and standardized.Using the traditional Chinese medicine inheritance auxiliary platform V2.5 to construct the prescription database,the frequency statistics,the efficacy statistics of the property,flavor,and meridian,association rule analysis,and cluster analysis were carried out to explore the medication rules and core compatibility prescription of Professor Fan Guanjie in the treatment of gouty arthritis.2.Network pharmacology research:Based on network pharmacology and molecular docking technology,the mechanism of Fan’s gout decoction in treating gouty arthritis was discussed.Network pharmacology and molecular docking technology were used to search the chemical constituents and targets of Lilium lily,Plantaginis,Polygonum cuspedeza,Tuporia cocos,Fritillaria vulgaris and Chrysanthemum wild in Fan’s Goufu recipe with the help of the Traditional Chinese Medicine System Pharmacology Analysis Platform(TCMSP).The chemical composition and targets of Lonicera japonica were supplemented with the help of the Encyclopedia of Chinese Medicine Platform(ETCM),and then the results of the two databases were merged.The corresponding targets of gouty arthritis were searched in GeneCards,OMIM,Disgenet,Drugbank,TTD,Drugbank and other databases,and then Cytoscape 3.7.1 was used to construct a compact-target(gene)network.After obtaining drugdisease intersection genes using Venny online website,the String database was used to obtain the core targets according to the Degree value,intermediate center value and close center value of the target,and the core target network was visualized by Cytoscape3.7.1 software.The intersection genes were transformed into entrezID,and P<0.05 and Q<0.05 were used as screening conditions in R language program.Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the intersection target genes to predict their mechanism of action.Finally,the molecular docking software(Autodock Vina)was used to simulate the docking of core components and core targets and verify the results.3.Prospective clinical study:Clinical study of Fan’s gout decoction in the treatment of acute gouty arthritis of damp-heat accumulation.A prospective,randomized controlled clinical trial was conducted.Sixty patients with acute gouty arthritis who met the inclusion criteria from June 2022 to December 2022 were randomly divided into treatment group and control group.The treatment group was given Fan’s gout decoction,one dose a day,one dose of decoction twice(strictly control the standard of each dose of medicinal materials and decoction,each time adding 2000ml of water,decocting to 1000ml,turning and decocting once,the decoction method was the same as above),a total of 2000ml of Chinese medicine for two times was mixed,one dose a day,a small amount of multiple times.The control group was given etoricoxib 120mg orally once a day.The treatment course of both groups was 7 days.Before and after treatment,the TCM syndrome score,joint local symptom and sign score,visual analogue scale(VAS)score,inflammatory indexes(CRP,ESR,IL-6,TNF-α,NLR,PLR),metabolic indexes(UA,blood lipid),and safety indexes were observed in the two groups.The clinical efficacy and safety of Fan’s gout decoction were evaluated by statistical analysis.Results1.Clinical retrospective study(1)Basic data analysis:a total of 693 patients were included in this study,91.77%of the total were males,8.23%were females,and the male to female ratio was about 11.2:1.The patients were mostly concentrated in 30-50 years old,with an average age of 44 years old(44.26±14.12).The proportion of male patients was significantly higher than that of female patients,and the age of onset was mainly young and middle-aged,showing a younger trend.The main TCM syndrome was damp-heat accumulation syndrome,accounting for 82.40%.(2)Analysis of the frequency of TCM:Among the 693 prescriptions included,88 TCM were involved,with a total frequency of 7104.A total of 17 herbs were used more than 100 times,accounting for 88.68%of all drug use frequency.Among them,10 TCM were used more than 300 times,accounting for 69.48%.Lily,soil poria,fritillary,honeysuckle vine,Polygonum cuspidatum,Psyllium plantaglium,wild chrysanthemum,wormwood,peony bark,coix seed.The efficacy of high frequency drugs is mainly heat-clearing drugs and moisture-enhancing drugs.(3)Analysis of tropism of TCM:Among the 693 prescriptions,cold,warm and flat drugs were the main drugs,accounting for 93.82%,and no hot drugs were used.Bitter,sweet and pungent drugs are the main drugs,accounting for 98.58%,and sour,salty and astringent drugs are seldom used.The drugs that belong to the liver meridian have the largest number of flavors and the highest frequency of medication,followed by those that belong to the stomach meridian,lung meridian,heart meridian,kidney meridian and spleen meridian,and the frequency of the above meridians is more than 1000 times.(4)Analysis of association rules of traditional Chinese medicine:Set the support threshold as 45%and the confidence as≥0.8,and get the core drug combination as Smilax glabra,Bulbus Fritillariae Cirrhosae,Lily,Plantago Plantaginis,Lonicera japonica Thunb,Polygonum cuspidatum and Flos Chrysanthemi Indici.(5)Drug cluster analysis:drug pairs with high correlation coefficient were obtained by entropy clustering algorithm,and eight potential drug core combinations,such as Leafplantaginis-Guanghuangbai,Paeony-licorice-Forsythia,lotus leaf-areca-hawthorn,curcumasalvia miltiorrhiza-yam-motherwort,were obtained,and four new prescriptions,such as Leaf-plantaginis-Phellodendron-Atractylodes-areca-tangerine,Curcuma-salvia miltiorrhizayam-motherwort-rhubarb-astragalus.The new prescription has the functions of benefiting qi,strengthening spleen,clearing heat,promoting diuresis,eliminating phlegm,promoting qi circulation and removing blood stasis,and can be used in clinical syndrome differentiation.2.Network pharmacology researchA total of 55 active ingredients and 261 corresponding targets of Fan’s gout decoction were found,and 72 intersection targets of active ingredient compounds and clinical targets were found,and 46 compounds related to the treatment of gouty arthritis were screened out.Network pharmacology analysis of the core combination showed that the top three core components were quercetin,luteolin,and naringenin.The main targets were RELA,IL6,TNF,MAPK14,MAPK3,MAPK1,FOS,NFKB1,IL10,NR3C1,etc.GO functional enrichment analysis obtained 2103 GO terms(P<0.05),of which 1974 were biological process(BP)terms,23 were cell composition(CC)terms,and 106 were molecular function(MF)terms.KEGG pathway enrichment screening identified 167 signaling pathways(P<0.05),mainly involved in inflammatory pathways(IL-17 signaling pathway,TNF signaling pathway,etc.).Metabolic pathways(lipid metabolism and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis),etc.In addition,there are MAPK signaling pathway,Toll-like receptor signaling pathway,HIF-1 signaling pathway,NF-Kb pathway and other pathways.Molecular docking results showed that quercetin,luteolin,naringenin and other active ingredients had excellent binding ability to multiple targets such as RELA,IL6,TNF,MAPK14,MAPK3,MAPK1,FOS,NFKB1,IL10,NR3C1 and so on.Among them,quercetin docking TNF(binding energy:-8.7 kj/mol),luteolin docking TNF(binding energy:-8.6 kj/mol),naringenin docking TNF(binding energy:-8.8 kj/mol).3.Prospective clinical study(1)Basic information and baseline data analysis:In this study,30 patients were included in each group for efficacy analysis.There was no significant difference in gender,age,course of disease,weight,height,BMI,and past medical history between the two groups(P>0.05).There was no significant difference in clinical observation indexes(TCM syndrome score,VAS score,joint pain score,joint tenderness score,joint swelling score,joint range of motion score,symptom and sign score,laboratory indexes)between the two groups(P>0.05).(2)Overall efficacy:In the treatment group,the ineffective,effective,markedly effective and cured rates were 6.7%,26.7%,46.7%and 20.0%,respectively,and the total effective rate was 93.3%.In the control group,the ineffective,effective,markedly effective and cured rates were 20.0%,53.3%,23.3%and 3.3%,respectively,and the total effective rate was 80.0%.The total efficacy of the treatment group was better than that of the control group(P<0.05).(3)TCM syndrome scores:after treatment,the TCM syndrome scores of the two groups were lower than those before treatment(P<0.05),and the degree of decline in the treatment group was better than that in the control group(P<0.05).(4)Visual analogue scale(VAS)scores:the VAS scores of the two groups after treatment were lower than those before treatment(P<0.05),and the VAS scores of the two groups after treatment were similar,the difference was not statistically significant(P>0.05).(5)Joint local symptom score:the joint pain score and joint tenderness score of the two groups after treatment were lower than those before treatment(P<0.05).The joint pain score and joint tenderness score of the two groups after treatment were similar,and the difference was not statistically significant(P>0.05).After treatment,the joint swelling score,joint activity score,symptom and sign score of the two groups were lower than those before treatment(P<0.05),and the treatment group was better than the control group in improving joint swelling score,joint activity score,symptom and sign score(P<0.05).(6)Inflammatory indicators:the two groups of treatment methods could reduce the levels of ESR and CRP(P<0.05),the treatment group was better than the control group(P<0.05).After treatment,the levels of IL-6 and TNF-α in the two groups were lower than those before treatment(P<0.05),and the curative effect in the treatment group was better than that in the control group(P<0.05).Compared with before treatment,the two groups could effectively reduce NLR and PLR after treatment(P<0.05),and the efficacy of the two groups was similar(P>0.05).(7)Metabolic indicators:only the treatment group could effectively reduce the UA level after treatment(P<0.05),while the control group had no significant change in UA level after treatment(P>0.05).After treatment,the levels of TG and TG/HDL-C in the treatment group were lower than those in the control group,and the difference was statistically significant(P<0.05).The levels of TG and TG/HDL-C in the treatment group after treatment were lower than those before treatment(P<0.05).(8)Safety:the frequency of adverse reactions in the treatment group(3.33%)was lower than that in the control group(20.00%),suggesting that the safety of the treatment group was better than that of the control group.Conclusion1.Professor Fan Guanjie used drugs in the treatment of gouty arthritis mainly cold,warm and flat,bitter,sweet and spicy drugs,drugs to liver channel,stomach channel and lung channel,high-frequency drugs to clear heat,water and moisture-draining drugs.Through the analysis of high-frequency drugs and association rules,the treatment of core drug combinations:Tuckahoe,Tubecia,lily,psyllium,honeysuckle,Polygonum cuspidatum,wild chrysanthemum,combined with clinical induction to form Fan’s gout decoction,and the potential drug combinations for the treatment of gout,to provide a new prescription for clinical treatment of this disease.2.In this study,network pharmacology and molecular docking technology were used to analyze and predict the mechanism of Fan’s gout decoction for gouty arthritis.It was found that quercetin,luteolin and naringenin,the main active components of Fan’s gout decoction,acted on RELA,IL-6,TNF,MAPK14 and other targets.It may regulate the body’s response to the control of inflammation,lipopolysaccharide and oxidative stress by regulating the inflammatory pathway,metabolism-related pathway,MAPK pathway,etc.It may interfere with gouty arthritis from multiple angles.It provides theoretical basis and scientific basis for further clinical research on Fan’s gout decoction in the treatment of acute gouty arthritis.3.Fan’s gout decoction plays an obvious role in anti-inflammation,swelling and pain relief for acute gouty arthritis(damp-heat accumulation syndrome),improves TCM syndrome score,effectively reduces inflammatory indicators,improves metabolic indicators such as UA and TG,and has high safety,no serious adverse events occur,which is worthy of further clinical promotion and application. |
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