| Objective(1)The network meta-analysis was used to compare the efficacy of different moxibustion therapies on rheumatoid arthritis(Rheumatoid Arthritis,RA),aiming to determine the best treatment for RA and provide guidance for the application of moxibustion in traditional Chinese medicine nursing technology.(2)The lipidomics technology of high performance liquid chromatography-mass spectrometry was used to explore the potential lipid biomarkers of RA,as well as the potential targets and network pathways of moxibustion in the treatment of RA in order to clarify the mechanism of moxibustion in treating RA and provide a basis for the application of moxibustion in traditional Chinese medicine nursing technology.Methods(1)Network Meta-analysis:a comprehensive and systematic search of PubMed,Web of Science,Embase,Cochrane Library,EBSCO and four Chinese databases(Wanfang,CNKI,SinoMed and VIP)were conducted.The retrieval time was from the establishment of the database to October 30,2020.The language was limited to Chinese and English.According to the inclusion and exclusion criteria,two researchers independently conducted literature screening and data extraction.The quality of the included randomized controlled trials was assessed independently by two reviewers using the Cochrane bias risk assessment tool.The ’mvmeta’ and ’network’packages in Stata 15.0 were used for network meta-analysis.(2)Study on lipidomics mechanism:32 SD rats were taken as the research object and 16 rats selected at random were induced to establish RA model with bovine type Ⅱ collagen.After successful modeling,they were randomly divided into 4 groups,namely control group,model group,moxibustion control group and moxibustion group,each group of eight.Among them,the control group and the model group were not treated,and the moxibustion group and the moxibustion control group were treated with moxibustion for 3 weeks.Morphological manifestations,body weight,toe volume,arthritis index,thymus and spleen index,serum inflammatory factors and ankle joint histopathology of the 4 groups of rats were compared.The incidence of rats and the efficacy of moxibustion in treating RA were evaluated by the above indexes.The plasma samples were collected 3 weeks after intervention,and lipid metabolism profiles of rats in each group were analyzed based on liquid lipidomics technology to explore potential biomarkers related to RA and the mechanism of moxibustion treatment of RA.Results(1)Network Meta-analysis:①Clinical effectiveness:indirect moxibustion+western medicine,suspended moxibustion+western medicine,warm moxibustion+western medicine,indirect moxibustion and suspended moxibustion were better than western medicine in terms of effectiveness.Indirect moxibustion+western medicine,suspended moxibustion+western medicine,warm moxibustion+western medicine,indirect moxibustion and suspended moxibustion were better than traditional Chinese medicine in terms of efficiency.Other paired comparisons showed no statistically significant differences between groups.Based on the results of network meta-analysis of all the above interventions,the top 3 moxibustion treatments in terms of clinical effectiveness were:warm moxibustion+western medicine(83.9%),suspended moxibustion+western medicine(79.1%)and indirect moxibustion+western medicine(74.3%).②Erythrocyte sedimentation rate(ESR):suspended moxibustion+western medicine had better effect on ESR reduction than indirect moxibustion+western medicine,warm moxibustion+western medicine,suspended moxibustion,indirect moxibustion,traditional Chinese medicine,direct moxibustion+western medicine and western medicine;compared with western medicine,indirect moxibustion+western medicine had a more significant effect on reducing ESR.Other paired comparisons showed no statistically significant differences between groups.Based on the results of network meta-analysis of all the abovc interventions,the top 3 moxibustion treatments in ESR were:suspended moxibustion+western medicine(98.8%),indirect moxibustion+western medicine(74.7%)and warm moxibustion+western medicine(62.2%).③C-reactive protein(CRP):suspended moxibustion+western medicine had better efficacy in reducing CRP than thunder fire moxibustion+Chinese medicine,indirect moxibustion+western medicine,indirect moxibustion,warm moxibustion+western medicine,Chinese medicine,suspended moxibustion,direct moxibustion+western medicine and western medicine;thunder fire moxibustion+Chinese medicine had better effect on CRP reduction than Chinese medicine and western medicine.Compared with western medicine,indirect moxibustion+western medicine and warm moxibustion+western medicine can reduce CRP more significantly.Other paired comparisons showed no statistically significant differences between groups.Based on the results of network meta-analysis of all the above interventions,the top 3 moxibustion treatments in CRP were:suspended moxibustion+western medicine(100.0%),thunder fire moxibustion+Chinese medicine(77.9%)and indirect moxibustion+western medicine(61.7%).④Visual analog scal(VAS):The effect of warm moxibustion+Chinese medicine in reducing VAS was better than that of direct moxibustion+western medicine,indirect moxibustion+western medicine,indirect moxibustion,warm moxibustion+western medicine,western medicine and Chinese medicine;Compared with western medicine,direct moxibustion+western medicine can effectively reduce VAS.Other paired comparisons showed no statistically significant differences between groups.Based on the results of network meta-analysis of all the above interventions,the top 3 moxibustion treatments in terms of VAS were:warm moxibustion+traditional Chinese medicine(100.0%),direct moxibustion+western medicine(69.1%)and indirect moxibustion+western medicine(68.9%).(2)Research on lipidomics mechanism:①Before modeling,there was no statistical difference in body weight,toe volume and arthritis index of rats in each group(P>0.05).After moxibustion treatment,the general condition of the rats in the moxibustion model group was improved,with their body weight increasing significantly compared with the model group,and the difference between these groups statistically significant(P<0.05);compared with the model group,the toe volume decreased significantly in the moxibustion model group,and the difference between two groups was statistically significant(P<0.05);the arthritis index of rats in the moxibustion model group gradually decreased,and the difference between these groups was statistically significant(P<0.01).Compared with the model group,the levels of IL-18,IL-6,and TNF-α in the moxibustion model group were significantly reduced,and the difference between two groups was statistically significant(P<0.05).Compared with the model group,the histopathological conditions of the ankle cartilage,synovium and inflammatory cell infiltration of the rats in the moxibustion model group were more alleviated②Differential lipid metabolites:through statistical analysis,a total of 33 differential lipid metabolites were screened and identified between the model group and the control group,mainly FA and TG.Among them,the relative content of 31 different lipid metabolites in the moxibustion group was statistically different from that in model group(P<0.05).Moxibustion increases DG,FA,and TG substances with a carbon chain length greater than 54,and down-regulates PC,LPC,PE and TG substances with a carbon chain length less than 54 in RA rats,so that the relative content will reach normal level after intervention.In addition,the relative content of 21 different metabolites in the moxibustion control group was statistically different from that in control group(P<0.05).Moxibustion can down-regulate PC,LPC and most TG substances with a carbon chain length less than 54,and up-regulate most TG substances with a carbon chain length greater than 54.③Metabolic pathway analysis:moxibustion may have a certain regulatory effect on the lipid metabolism of rats in different body states.Lipid metabolism is closely related to RA.Under pathological conditions,the potential main metabolic pathways regulated by moxibustion in the treatment of RA are α-linolenic acid metabolism and glycerophospholipid metabolism.Under physiological conditions,the potential main metabolic pathway regulated by moxibustion is glycerophospholipid metabolism.Conclusions:(1)The comprehensive therapy of moxibustion combined with drugs is better than single drug therapy,and the combination of western medicine is more common than traditional Chinese medicine in clinical practice.The combined therapy of suspended moxibustion+western medicine,indirect moxibustion+western medicine,warm moxibustion+western medicine or traditional Chinese medicine may be the potential best method for the treatment of RA,which provides new evidence and insights for the clinical treatment of RA.However,the quality and quantity of the included studies are limited,so the positive results of this network meta-analysis need to be interpreted very carefully.More high-quality randomized controlled trials are needed to confirm the exact conclusion in the future.(2)Moxibustion can improve the general condition and body weight of RA rats,reduce foot swelling,arthritis index and cytokine levels,and improve the pathological condition of ankle joint tissues,indicating that moxibustion is an effective way to treat RA.(3)RA rats have obvious lipid metabolism disorders,among which 33 different lipid metabolites may be potential biomarkers of RA.Comprehensively different metabolites change between the moxibustion group and the model group,the moxibustion control group and the control group,regardless of whether the rat in a physiological or pathological state,moxibustion can down-regulate PC,LPC and most TG substances with a carbon chain length less than 54,and up-regulate the relative content of most TG substances with a carbon chain length greater than 54.In a disease state,moxibustion can also up-regulate DG and FA,and down-regulate PE to regulate lipid metabolism disorders in RA rats.(4)Moxibustion may have a certain regulatory effect on the rat’s physiological and pathological lipid metabolism,and the potential main metabolic pathway involved is glycerophospholipid metabolism. |
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