Clinical Observation And Mechanism Exploration Of The Treatment Of Primary Premature Ejaculation With The Treatment Of Liver Qi Stagnation By The No.2 Formula

Objective:1.To evaluate the clinical effect of the formula No.2 on primary premature ejaculation with liver depression and qi stagnation.2.Network pharmacology: To explore the potential mechanism of premature ejaculation prescription No.2 in the treatment of primary premature ejaculation.Method:1.Randomized and controlled study:From December 2020 to December 2022,patients with primary premature ejaculation of liver depression and qi stagnation in the male outpatient department of the First Affiliated Hospital of Anhui University of Chinese Medicine were the case sources for this study.A clinical prospective study was conducted,and 90 subjects were randomly divided into the Chinese medicine group and the Western medicine group,45 in each group.Baseline data of subjects in the two groups were as follows: There was no significant difference in general data,PEP,PEDT,IELT and TCM syndrome scores(P >0.05).The traditional Chinese medicine group was given Zanxi No.2 Fang granules,one dose a day,200 ml boiled water,once in the morning and once in the evening.In the western medicine group,Dapoxetine hydrochloride was taken orally 2 hours before the same room,30 mg each time,six consecutive times as a course of treatment.After 12 weeks of treatment(8 weeks of medication,4 weeks of follow-up),the changes of TCM symptom score,IELT,PEDT and PEP were compared between the two groups before and after treatment.2.Network pharmacological research: Obtained the active chemical constituents,active ingredients,corresponding prediction targets of active ingredients,and corresponding disease prediction targets of PPE of prescription No.2 from several free and open databases,drew Wayne intersection diagram to screen out the target of action of prescription No.2 for the treatment of PPE,and built a "drug-composition-target" model with the help of software.The protein interaction network was constructed by the target,and the core network was calculated and screened to obtain the core target and core components.Core target functional enrichment analysis was performed to obtain the main pathway of treatment of PPE by premature ejaculation No.2 formula,and a "component-target pathway" model was constructed,so as to explore the possible mechanism of treatment of primary premature ejaculation by premature ejaculation No.2 formula.Result:1.Randomized,controlled study:(1)A total of 90 patients were enrolled,and there was no significant difference in baseline data of age,course of disease,PEP,PEDT,IELT and TCM syndrome scores between the two groups(P > 0.05).After excluding the shedding index,37 patients remained in the Chinese medicine group and 38 in the western medicine group.(2)After treatment,the PEP score in the TCM group was increased from(4.36±1.72)points to(10.40±1.79)points;In the western medicine group,PEP score increased from(4.78±1.84)to(7.67±2.46).Before and after treatment,PEDT score was decreased,PEP score was increased and IELT time was prolonged in both TCM group and Western medicine group(P < 0.05).The TCM group could effectively reduce the TCM syndrome score throughout the whole process(P < 0.05),while the western medicine group could not reduce the TCM syndrome score(P > 0.05).(3)Compared with the western medicine group in the same period,the Chinese medicine group had a long delay of IELT,while the western medicine group showed a decrease in efficacy after withdrawal(P < 0.05);The period of PEP improvement in the Chinese medicine group was shorter(P < 0.05).(4)Safety evaluation: A total of 8 cases of mild adverse events occurred during the study period,including 3 cases in the Chinese medicine group and 5 cases in the Western medicine group.The symptoms of adverse reactions were self-alleviated after medical guidance,and no serious adverse reactions were observed.There were no obvious abnormalities in blood routine,urine routine,liver function(ALT,AST,AST/ALT),renal function(BUN,Scr,Ucr)and bedside electrocardiogram in the two groups.2.Network Pharmacology Research:(1)After database screening and literature reference comparison,a total of 761 compounds of Formula 2 for premature ejaculation were obtained,and 170 effective compounds were obtained after screening and removal of repeated compounds in a single drug.(2)After searching through multiple target prediction platforms,partial weight removal was carried out,and 1017 disease prediction targets of PPE were obtained after analysis.After intersection with 761 active ingredients,140 targets of premature ejaculation No.2 prescription were obtained for PPE treatment.(3)The ranking was obtained by the number of connections between PPI central node and other nodes.AKT1,HRAS,ESR1,HSP90AA1,AR,MAPK1,NFKB1,IGF1 R,AKR1C3 and NFKBIA were the top ten target genes.(3)80 CC,451 BP and 140 MF were obtained after GO analysis.(5)KEGG enrichment analysis of Premature ejaculation No.2 formula in the treatment of PPE signaling molecules of Alzheimer’s disease,neurodegenerative pathway,PI3K-Akt,cAMP,estrogen and other pathways score higher.Conclusion:1.Randomized,controlled studies:(1)Formula No.2 of premature ejaculation can effectively improve PEP questionnaire score and IELT value,so as to delay ejaculation and improve subjects’ sense of sexual experience.Prescription No.2 also outperformed dapoxetine in reducing the PEDT questionnaire score after 8 weeks of treatment.Premature ejaculation No.2 can reduce TCM syndrome score,Dapoxetine does not have this effect.The comprehensive income effect of formula 2 for premature ejaculation is more advantageous than that of dapoxetine.(2)Formula No.2 can treat primary premature ejaculation of liver depression and Qi-stagnation type,and no serious adverse reactions were observed during the study,suggesting that formula No.2 has good safety in treating primary premature ejaculation of liver depression and Qi-stagnation type.2.Network Pharmacology Research:(1)Formula 2 for premature ejaculation has the characteristics of "multi-component,multi-target-multi-pathway" in the treatment of PPE.(2)Formula 2 for premature ejaculation may play a role in treating PPE by activating or inhibiting the pathway of Alzheimer’s disease,neurodegeneration,PI3K-Akt,cAMP,estrogen and other signaling pathways.