| ObjectiveIn the clinical study,a historical cohort study was used to retrospectively analyze the pregnancy rate of patients with mild to moderate endometriosis complicated with infertility confirmed by laparoscopy and pathology within two years after operation,and to compare the clinical efficacy of Luo’s Neiyi prescription,Gn RH-αand their combination in improving fertility,in order to serve the clinical decision-making.In the study of network pharmacology,the key targets of Luo’s Neiyi prescriptionin the treatment of EMs were obtained through the database,and the "drug-active ingredient-key target" network diagram and protein interaction network diagram were constructed with the help of Cytoscape software,and the key targets were analyzed by KEGG and GO enrichment analysis,so as to improve the molecular mechanism of Luo’s Neiyi prescription in the treatment of EMs and endometriosis infertility.It is theoretically clear that Luo’s Neiyi prescription can interfere with the "AAA" process of endometriosis through the key targets: ICAM-1,MMP-9 and VEGFA,so as to provide theoretical basis for the clinical efficacy of Luo’s Neiyi prescription.MethodsIn the clinical study,from January 2015 to December 2018,patients with II and III endometriosis with infertility confirmed by laparoscopy and postoperative pathology in our hospital were divided into four groups according to their postoperative treatment: Luo’s Neiyi prescription group,Gn RH-αgroup,Luo’s Neiyi prescription combined with Gn RH-αgroup and control group(that is,without Luo’s Neiyi prescription and Gn RH-α).After operation,all patients were treated with Siwu decoction to promote postoperative recovery.The postoperative treatment plan and pregnancy within two years were followed up by telephone.In the study of network pharmacology,the main active components of Luo’s Neiyi prescription were screened by TCMSP database and BATMAN-TCM database,the action targets of the main active components probability> 10% were obtained by Swiss Target Prediction database,the related targets of endometriosis were searched by Gene Cards database and Drug Bank database,and the active ingredient targets were mapped with disease targets.With the help of Cytoscape3.6.0 software,the network diagram of "drug-active ingredient-key target" was constructed,and the protein-protein interaction network of key targets was constructed and analyzed by STRING database.Finally,the GO and KEGG pathways of key targets were analyzed by g:profiler database.Results Clinical study:1.Luo’s Neiyi prescription group,Gn RH-αgroup,Luo’s Neiyi prescription combined with Gn RH-α,There was no significant difference in age,infertility and duration of infertility between the two groups(P > 0.05).2.Luo’s Neiyi group,Luo’s Neiyi combined with Gn RH-α,the difference of pregnancy rate in the first year and the second year after operation was statistically significant(P<0.05);There was no significant difference between the other two groups(P > 0.05).3.Luo’s Neiyi group and control group,Gn RH-αgroup and control group,Luo’s Neiyi prescription combined with Gn RH-α Compared with the control group,the difference of pregnancy rate in two years after operation was statistically significant(P < 0.0083),and there was no significant difference between the other two groups(P > 0.0083).4.There was significant difference in the first year pregnancy rate between the two groups(2 = 28.232,P < 0.05).5.There was no significant difference in the pregnancy rate in the first year between the two groups(P > 0.05).6.Gn RH in patients with ASRM stage II endometriosis and infertility-α Group A and control group,Luo’s Neiyi combined with Gn RH-α There was significant difference in the pregnancy rate between the two groups(P < 0.0083),but there was no significant difference between the other two groups(P>0.0083);Patients with ASRM III endometriosis complicated with infertility were divided into two groups: Luo’s Neiyi prescription group and control group,Luo’s Neiyi prescription combined with Gn RH-α Compared with the control group,there was significant difference in the two-year pregnancy rate between the two groups(P< 0.0083),but there was no significant difference between the other two groups(P>0.0083).7.LF(fallopian tube function)score 5-8 groups: Luo’s Neiyi prescription group and control group,Gn RH-αgroup and control group,Luo’s Neiyi prescription combined with Gn RH-α,There was significant difference in pregnancy rate between the two groups(P <0.0083),but there was no significant difference between the other two groups(P > 0.0083);LF score 0-4 group: Lou’s Neiyi formula combined with Gn RH-αcompared with the control group,there was significant difference in the two-year pregnancy rate between the two groups(P < 0.0083),but there was no significant difference between the other two groups(P > 0.0083).8.EFI(endometriosis fertility index)score 6-10 grouping: Luo’s Neiyi prescription group and control group,Gn RH-αgroup and control group,Luo’s Neiyi prescription combined with Gn RH-α,There was significant difference in pregnancy rate between the two groups(P< 0.0083),but there was no significant difference between the other two groups(P> 0.0083);EFI score 0-5 group: there was no significant difference among the four groups(P> 0.05).9.There were significant differences in LF score and EFI score between pregnant group and non pregnant group(P< 0.05),but there was no significant difference in ASRM score(P> 0.05).10.There was a negative linear relationship between ASRM and LF,EFI,and a positive linear relationship between LF and EFI.11.Luo’s Neiyi prescription group,Gn RH-αgroup,Luo’s Neiyi prescription combined with Gn RH-α,there was no significant difference in adverse reactions between the two groups(P>0.05).Network pharmacology research:The network analysis of "drug active ingredient key target" showed that the treatment of EMS with Luo’s Neiyi prescription mainly involved 131 active ingredients and 285 key targets;PPI network analysis showed that the key targets of Luo’s Neiyi prescription in the treatment of EMs included: interleukin-6(IL-6),intercellular adhesion molecule-1(ICAM-1),matrix metalloproteinase-9(MMP-9),vascular endothelial factor A(VEGFA),tumor necrosis factor(TNF),etc;The enrichment analysis of go gene and KEGG pathway indicated that Luoshi Neiyi decoction could treat EMs through 1599 biological processes,including cell proliferation,cell migration,inflammatory response,hormone response,etc;It involves 78 pathways,including adhesion plaque,PI3 K Akt signaling pathway,TNF signaling pathway,FOXO signaling pathway,MAPK signaling pathway and so on.ConclusionClinical study:1.Luo’s Neiyi prescription,Gn RH-α、Luo’s Neiyi prescription combined with Gn RH-α,all the three treatments can improve the pregnancy probability within two years after operation in patients with stage II and III endometriosis combined with infertility.2.Continuous use of Luo’s Neiyi prescription for 3 months or more can significantly improve the first year pregnancy probability of patients with stage II and III Neiyi complicated with infertility.3.For patients with stage II endometriosis and infertility,Gn RH-αshould be used combined use of Luo’s Neiyi prescription can further improve the pregnancy outcome;For patients with stage III endometriosis and infertility,Luo’s Neiyi prescription combined with Gn RH was used-α The treatment can improve the pregnancy rate within two years after operation.4.There was no significant correlation between ASRM score and postoperative pregnancy outcome of patients with endometriosis infertility,but the lower the stage,the higher the pregnancy rate;The higher the scores of LF and EFI,the higher the probability of pregnancy in patients with endometriosis infertility.5.The higher the LF score is,the higher the probability of pregnancy within two years after operation is;For the patients with low lf score,Neiyi prescription combined with Gn RH-α,The treatment can improve the pregnancy rate within two years after operation.6.The higher the EFI score is,the higher the probability of pregnancy within two years after operation is;For the patients with lower EFI score,the treatment schemes had no significant effect on improving the pregnancy rate within two years after operation.7.Gn RH-αwas used in the probability of adverse reactions is small,which has more advantages in improving the treatment compliance of patients.Network pharmacology research:1.Luo’s Neiyi prescription has influence on the pathogenesis and pathological mechanism of endometriosis infertility,such as inflammation,endocrine imbalance,"AAA" process,immune abnormality,etc.it is speculated that it can treat endometriosis infertility through complex target pathway network mechanism.2.Luo’s Neiyi prescription can regulate the AAA process of ectopic lesions by regulating the three representative factors of AAA process: ICAM-1,MMP-9 and VEGF-A.it provides new ideas and clues for further exploring the potential mechanism of Luo’s Neiyi prescription in the treatment of EMS. |
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