Objective1.To systematically evaluate the efficacy and safety of acupuncture combined with medicine in the treatment of inactive thyroid-related ophthalmopathy;2.Randomized controlled clinical trials were conducted to evaluate the efficacy and safety of acupuncture combined with medicine in the treatment of inactive thyroid-related ophthalmopathy;3.The molecular biological mechanism of Pingmu decoction in the treatment of Graves ophthalmopathy in inactive stage was studied by network pharmacology method.Methods:1.By computer and manual retrieval the Cochrane Library,Pub Med,EMbase and China hownet(CNKI),China science and technology periodical database(VIP),ten thousand,such as database collected in January 1986-December 2020 acupuncture combined drug therapy of thyroid related ophthalmopathy randomized controlled clinical trials,the methodological quality of the literature of included in the assessment and extract the effective data,USES the Review Manager 5.3 software for meta analysis.2.To 120 cases of non activity TAO card belong to deficiency,phlegm and blood stasis block of sun be the spirit of the patients were randomly divided into needle medicine group(n = 40),Chinese medicine group(n = 40),acupuncture group(n = 40),needle medicine group to flat soup with acupuncture therapy,Chinese medicine group in the flat mesh orally,pure acupuncture therapy,acupuncture group all the subjects maintain TAO foundation treatment,treatment for 12 weeks.The degree of ocular protrusion and TCM syndrome scores of the three groups before and after treatment were observed,and the adverse reactions were recorded to evaluate the clinical efficacy and safety.3.Using network pharmacological method,taking Pingmu Decoction(composed of Astragalus membranaceus,Xianling Spleen,Salvia miltiorrhiza,Hedyotis officinalis,Chinese mustard seed and Plantago seed)as the research object,the chemical composition data set of Pingmu Decoction,the screening of active ingredients and the prediction of drug targets,and the potential action target information data set of the active ingredients of Pingmu Decoction were constructed.Through OIMI,Gene Cards,NCBI,CTD and other databases,the genes related to TAO were found,and the target interaction network was constructed to collect candidate targets of Pingmu Decoction for the treatment of inactive TAO.Finally,the Gene ontology function of the target and the enrichment of KEGG metabolic pathway were analyzed.To explore the possible molecular mechanism of Pingmu decoction in the treatment of inactive thyroid-associated ophthalmopathy,it provides a reference for further experimental verification.Results:1.Systematic evaluation :Seven of the eighteen literatures were finally screened and included,with a sample size of 44~83 cases and a total sample size of 400 cases,including 208 cases in the acupuncture and drug combination group and 192 cases in the control group,with a course of 3~6 months.Meta-analysis results showed that:Acupuncture and drug combination therapy vs.drug treatment alone improved degree of ocular outburst MD=-1.45,95%CI(-1.90,-1.00),P<0.001;effective rate RR=1.48,95%CI(1.26,1.75),P<0.001;clinical efficacy RR=1.48,95%CI(1.30,1.69),P<0.001.The difference was statistically significant.The acupuncture group was better than the single drug group.No serious adverse reactions were observed.2.Clinical research:(1)Eye bulging degree: After treatment,the total effective rate was95.00% in the acupuncture group,74.36% in the Chinese medicine group,and 53.85% in the acupuncture group,with statistically significant differences among the three groups after treatment(P<0.01).Among them,the comparison between acupuncture and medicine group and Chinese medicine group,Chinese medicine group and acupuncture group(P<0.05),and the comparison between acupuncture and medicine group and acupuncture group(P<0.01).Among the three groups,the acupuncture group had the best curative effect.After treatment,the degree of ocular protrusion in the three groups decreased compared with that before treatment,with statistical significance(P<0.05).Among the three groups,the degree of ocular protrusion in the acupuncture and medicine group,Chinese medicine group and acupuncture and moxibustion group decreased the most obviously.After treatment,the difference between the three groups was statistically significant(P<0.01).Among them,the comparison between acupuncture and medicine group and Chinese medicine group and acupuncture group was significant(P<0.05).Acupuncture group was compared with acupuncture group(P<0.01).Among the three groups,the reduction of eye protrusion in the acupuncture group was better than that in the Chinese medicine group and the acupuncture group.After treatment,the difference of ocular protrusion degree among the three groups was statistically significant(P<0.01).Among them,the comparison between acupuncture and medicine group and Chinese medicine group,Chinese medicine group and acupuncture group(P<0.05),and the comparison between acupuncture and medicine group and acupuncture group(P<0.01).Among the three groups,acupuncture and medicine group had the most significant decrease in protrusion degree of patients.(2)Comparison of efficacy of TCM syndrome scores:After treatment,the total effective rate of the acupuncture and medicine group was 90.00%,the total effective rate of the Chinese medicine group was76.92%,and the total effective rate of the acupuncture and medicine group was 51.28%.There were statistically significant difference in the efficacy of TCM syndrome integral among the three groups(P<0.01).Among them,the acupuncture and medicine group was compared with the Chinese medicine group,the Chinese medicine group was compared with the acupuncture group(P<0.05),the acupuncture and medicine group was compared with the acupuncture group(P<0.01).Among the three groups,acupuncture and medicine group had the most significant effect of reducing TCM syndrome integral.After treatment,the total score of TCM syndromes in the three groups decreased compared with that before treatment(P<0.01),among which,the total scores of acupuncture and medicine group was compared with that of Chinese medicine group(P<0.05),the total score of acupuncture and medicine group was compared with that of acupuncture and medicine group,and the total score of Chinese medicine group was compared with that of acupuncture and medicine group(P<0.01).Among the three groups,acupuncture and medicine group had the most significant effect in reducing the total score of TCM syndromes.After treatment,the difference of TCM syndrome scores among the three groups was statistically significant(P<0.01).Compared with the traditional Chinese medicine group,the traditional Chinese medicine group and the acupuncture group(P<0.05),the acupuncture and medicine group and the acupuncture group(P<0.01).Among the three groups,acupuncture and medicine group had the most significant effect of reducing TCM syndrome integral.Comparison of curative effects of various TCM syndromes after treatment: after treatment,there were statistically significant differences in eyeball distend and pain,fatigue and spontaneous sweating among the three groups(P<0.01),among which the acupuncture and medicine group was compared with the acupuncture group(P<0.01),the acupuncture and medicine group was compared with the Chinese medicine group,and the Chinese medicine group was compared with the acupuncture group(P<0.05).After treatment,acupuncture and medicine group has the most significant effect on improving eyeball distension,fatigue and spontaneous sweating.(3)Thyroid function: there was no statistical difference between the three groups before and after treatment and between the three groups after treatment(P>0.05).(4)Adverse reactions: There was no statistical significance in the incidence of adverse reactions among the three groups(P>0.05).3.Network pharmacological study: Based on the parameters of oral availability(OB%)>30% and medicinal property(d L)>0.18,276 active components of Pingmu Decoction were screened for the treatment of inactive TAO,including 22 key components including flavonoids.It may act on 133 targets,including 58 critical targets.PI3K-Akt,MAPK,HIF-1 and so on were closely related to TAO in inactive phase.It may play a role in the treatment of TAO by acting on PTPN1,CXCL-8,CXCL-10,IL-10,IL-2,IL-17,MMP-9 and other targets.Conclusion:1.Acupuncture and medicine combined treatment of TAO is superior to drug therapy alone in improving clinical efficacy or reducing ocular protrusion,and can be popularized and applied in clinic.However,there are relatively few literatures on the combination of acupuncture and medicine in the treatment of TAO,and multi-center,large-sample randomized controlled clinical trials are still needed to further improve evidence-based medicine evidence.2.Acupuncture combined with medicine can effectively improve the TCM syndrome score of inactive Tao Yang Qi deficiency and phlegm and stasis syndrome patients,with a total effective rate of 90.00%,which is better than that of TCM group(76.92%)and acupuncture group(51.28)(P<0.01).The combination of acupuncture and medicine can significantly reduce the degree of eye protrusion in inactive TAO patients,and the total effective rate is 95.00%,which is better than that in TCM group and acupuncture group(P<0.01).There was no difference in the incidence of ADR between the acupuncture group and the TCM group and the acupuncture group.It has high security.3.Pingmu Decoction may act on multiple targets such as PTPN1,CXCL-8,CXCL-10,IL-10,IL-2,IL-17 and MMP-9 through PI3K-Akt,MAPK,HIF-1 and other pathways,and play an anti-oxidation and anti-fibrosis role in treating TAO.To provide the basis for the experimental study of the mechanism of Pingmu decoction. |