ABSTRACT
OBJECTIVE:There are many kinds of biological agents for the treatment of rheumatoid arthritis in clinic,but the differences in therapeutic efficacy and safety are still unclear.The purpose of this study is to compare the differences in effectiveness and safety of different biological agents for the treatment of rheumatoid arthritis. METHODS:CNKI,VIP,WanFang,China Biomedical Literature System,PubMed,Cochrane Library,Web of Science,and Embase databases were searched to collect the randomized controlled trials on biological agents for rheumatoid arthritis that meet the requirements from inception to October 1,2022.The literature was selected by EndNote software,and the quality of the included literature was evaluated by RevMan 5.3 software.The software Stata 14.2 was used for direct meta-analysis and network meta-analysis of ACR20(American College of Rheumatology 20%response),ACR50(American College of Rheumatology 50%response),ACR70(American College of Rheumatology 70%response),erythrocyte sedimentation rate,and adverse reactions. RESULTS:Totally 39 articles were included,including 5 low-risk articles,4 high-risk articles,and the remaining 30 articles contained unknown risk bias,with a total of 13 treatment measures.The results of network meta-analysis:(1)In ACR20,infliximab combined with methotrexate(OR=5.54,95%CI:1.33-23.01,P<0.05),abatacept+methotrexate tablets(OR=3.21,95%CI:1.13-9.10,P<0.05),and tocilizumab(OR=2.95,95%CI:1.61-5.44,P<0.05)were better than methotrexate tablets.The probabilistic ranking of ACR20 was:infliximab+methotrexate tablets>abatacept+methotrexate tablets>tocilizumab>certlizumab>etanercept+methotrexate tablets.(2)In the aspect of ACR50,etanercept combined with methotrexate tablets(OR=4.04,95%CI:2.13-7.66,P<0.05),infliximab combined with methotrexate tablets(OR=4.79,95%CI:1.19-19.26,P<0.05),and tocilizumab combined with methotrexate tablets(OR=3.54,95%CI:1.36-9.22,P<0.05)had better therapeutic effects than methotrexate tablets.The probabilistic ranking of ACR50 was:etanercept+methotrexate tablets>infliximab+methotrexate tablets>tocilizumab+methotrexate tablets>tocilizumab>certlizumab+methotrexate tablets.(3)In terms of ACR70,the therapeutic effects of infliximab combined with methotrexate tablets(OR=8.00,95%CI:2.31-27.69,P<0.05),etanercept combined with methotrexate tablets(OR=4.26,95%CI:2.51-7.21,P<0.05),and tocilizumab combined with methotrexate tablets(OR=3.51,95%CI:1.82-6.80,P<0.05)were better than methotrexate tablets.The probabilistic ranking of ACR70 was infliximab+methotrexate tablets>etanercept+methotrexate tablets>tocilizumab+methotrexate tablets>certlizumab>adalimumab+methotrexate tablets.(4)In erythrocyte sedimentation rate,etanercept combined with methotrexate tablets(SMD=-9.23,95%CI:-16.55 to-1.92,P<0.05)was better than etanercept and methotrexate tablets(SMD=14.59,95%CI:7.28-21.91,P<0.05).The probabilistic ranking of erythrocyte sedimentation rate was etanercept+methotrexate tablets>infliximab+methotrexate tablets>etanercept>adalimumab+methotrexate tablets>methotrexate tablets.(5)In terms of adverse reactions,placebo(OR=0.62,95%CI:0.39-0.99,P<0.05)was better than infliximab and certlizumab(OR=0.44,95%CI:0.25-0.78,P<0.05).The probabilistic ranking of adverse reactions was placebo>infliximab>etanercept+methotrexate tablets>certlizumab>etanercept. CONCLUSION:Based on evidence from 39 randomized controlled trials,infliximab combined with methotrexate tablets(highly recommended)can be the first choice in clinic,and etanercept combined with methotrexate tablets(highly recommended)can be the second choice in terms of good effectiveness and safety.
ABSTRACT
Objective To explore the effects of glutamine (Gln) on tumor necrosis factor-alpha (TNF-α),interleukin-6(IL-6),and interleukin-10 (IL-10) in rats with severe acute pancreatitis (SAP).Methods 54 Sprague-Dawley rats were randomly divided into 3 groups ( n =18 for each group):Gln treatment group ( Gln),SAP model group (SAP),and negative control group (NC).SAP was induced by injection of 4％ sodium taurocholate through common bile duct with a fine needle and the puncture hole in the bile duct was closed by medical sealant glue.Sham operation was performed in the rats of NC group.Rats in Gln group received Gln injection and rats in SAP group and NC group received normal saline instead of Gln.Ascites volume and blood amylase were measured at 3,6 and 12 hours after injection and plasma cytokines were detected by enzyme-linked immunosorbent assay (ELISA).Gross and histological changes of pancreas were evaluated by a scoring system.Results The ascites volume,serum amylase level,gross and histological scores,TNF-α level,and IL-6 level were significantly higher in SAP group than in NC group at each time point(P＜0.05).IL-10 level was significantly higher in SAP group than in NC group at 3 hour point(P＜0.05).The ascites volume,serum amylase level,and gross and histological scores were significantly lower in Gln group than in SAP group at the time point of 3 hour and 6 hour after injection( P ＜ 0.05 ).Level of TNF-α and IL-6 was significantly lower in Gln group than in SAP group at each time point( P ＜0.05 ).IL-10 level was lower in Gln group than in SAP group at 3 hour point( P ＜0.05 ).Conclusion Gln is effective in SAP treatment by decreasing the serum level of proinflammatory cytokine and ameliorating the pathological damage of pancreatic tissues in rats.
ABSTRACT
Objective To improve the establishment of severe acute pancreatitis model in rat. Methods 36 Sprague-Dawley rats were randomly divided into experiment or shame operation group(n=18,each). Severe acute pancreatitis was induced by injection of 4% sodium taurocholate through puncturing common bile duct with a fine needle, puncture hole was closed by medical sealant glue. Ascites volume and blood amylase were measured at 3, 6 and 12 hours after injection. Gross and histological changes of pancreas were evaluated by a scoring system. Results Pancreatic changes in the experiment group was hemorrhagic and necrosis.The ascites volume(8.52±1.05)ml,serum amylase activity(5247.17±547.07)u/L, gross and histological scores(13.6±3.92) in experiment group was significantly higher than ascites volume(1.21±0.32)ml,serum amylase activity(1289.5±176.67)u/L, gross and histological scores((0.83±0.58) in shame operation group at every time point(P<0.05). Conclusions Combined injection through common bile duct and medical sealant glue in the experiment can minimize the trauma and simplize the procedure. This method produces a reliable model with high success rate and it is an ideal severe acute pancreatitis animal model.