Objective:To understand the pathogens and molecular-epidemiologic characteristics of viral meningo-encephalitis in Zhejiang province during 2002 to 2018.Methods:All the samples were collected from suspected patients admitted to the hospitals under the monitoring program. Of the total samples, 2 173 were cerebrospinal fluids while the other 455 were stool specimens. Cerebrospinal fluid (CSF) samples were subject to real-time qPCR for the detection of Human enterovirus (HEV), Mumps virus (MuV), Herpes simplex virus (HSV), Cytomegalovirus (CMV) and Japanese encephalitis virus (JEV). Stool sample were subject to real-time qPCR for HEV. ELISA was used to detect the IgM antibodies in CSF, in the 5 kinds of virus mentioned above. VP1 genes from all RNA-positive specimen were amplified, sequenced, for typing and for evolution analysis.Results:871 (40.1 %) of the 2 173 samples were detected as HEV nucleic acid positive during 2002 to 2018. 654 (38.1 %) of the 1 718 CSF sample were HEV nucleic acid positive while 217 (47.7 %) of the 455 stool sample were HEV nucleic acid positive. Among the total positive nucleic acid sample, 670 of them were VP1 sequence positive, including 5 HEV-A and 665 HEV-B. There were 23 HEV serotypes, including Coxsackievirus (CV) CVA4, CVA6, CVA9, CVA10, CVB1-5, Echovirus (EchoV; E) E3, E4, E6,E7, E9, E11, E14, E16, E18, E21, E25, E30, E33 and EV-71. The top three serotypes went to E30, E6 and CVB5. These three serotypes presented enhanced viral activity in every several years. 795 CSF samples were detected as virus nucleic acid positive, including 374 HEV, 6 MuV, 5 HSV and 5 CMV, from 2012 to 2015 and in 2018. 5 kinds of IgM antibodies were detected simultaneously in 368 CSF samples, including 2 HEV positive, 6 JEV positive and 1 MuV positive for 5 viruses, respectively. Except for EV-71, there were 517 EchoV and 152 CV viruses presented, with the ratio of 3.4∶1. These two kinds of viruses alternately changed for each predominant epidemic strains in every 3-5 years. Based on VP1, results from the phylogenetic tree showed that HEV from Zhejiang province clustered into HEV-A and HEV-B clades respectively. E30 developed both h and i sub-genotypes. Conclusions:HEV-B seemed the main pathogen for viral meningo-encephalitis in Zhejiang province. Ratio of positive detection on EchoV was significantly higher than that on CV. These two kinds of virus alternately presented changing tendency in every several years. Predominant epidemic strains E30, CVB5 and E6 were presenting enhanced viral activity, also in every several years. High correlation was found in both HEV viral activity from the surveillance sites and in time line of the viral meningo-encephalitis outbreaks.

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1β(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.
Animals ; Arthritis, Rheumatoid/drug therapy* ; Cytokines ; Drugs, Chinese Herbal/therapeutic use* ; Glycosides/therapeutic use* ; Humans ; Leflunomide/therapeutic use* ; Methotrexate/therapeutic use* ; Tablets ; Tripterygium/chemistry*

To evaluate the clinical efficacy of single administration of Tripterygium Glycosides Tablets(TGT) or combined administration with methotrexate(MTX) against rheumatoid arthritis(RA) based on American College of Rheumatology(ACR) efficacy standard. Six databases, namely CNKI, WanFang, VIP, PubMed, Embase and Cochrane Library, were retrieved for randomized controlled trials(RCT), and clinical trials were screened out according to the preset inclusion and exclusion criteria. Then, the study quality was evaluated by the risk assessment tools. Data extraction and analysis were performed by using RevMan 5.3 software for Meta-analysis. Sensitivity analysis and publication bias analysis were made to test the stability and reliability of results. Until December 2018, a total of 1 709 articles were obtained, and finally 10 clinical RCT studies with a total of 1 184 patients were included. As a result, the single administration of TGT showed a significantly better ACR efficiency(RR=1.31, 95%CI[1.15, 1.49], P<0.000 1) than methotrexate(MTX). The combined administration of TGT and MTX showed a significantly better ACR efficiency(RR=1.28, 95%CI[1.20, 1.38], P<0.000 01) than the single administration of MTX. In conclusion, the single administration of TGT and the combined administration of TGT and MTX were more effective in achieving ACR20, ACR50, ACR70 compliance than the single administration of MTX. Further validations based on more RCT studies with high-quality are required.
Antirheumatic Agents/therapeutic use* ; Arthritis, Rheumatoid/drug therapy* ; Drug Therapy, Combination ; Drugs, Chinese Herbal/therapeutic use* ; Glycosides/therapeutic use* ; Humans ; Methotrexate/therapeutic use* ; Randomized Controlled Trials as Topic ; Reproducibility of Results ; Tablets ; Treatment Outcome ; Tripterygium/chemistry*

The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.
Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Glycosides ; therapeutic use ; Humans ; Methotrexate ; therapeutic use ; Randomized Controlled Trials as Topic ; Tablets ; Treatment Outcome ; Tripterygium ; chemistry

To systematically review the improvement effects of Tripterygium Glycosides Tables( TGT) alone or in combination with methotrexate( MTX) on the clinical signs and symptoms of rheumatoid arthritis( RA),and provide a basis for the rational use of TGT in clinic,in the current study,six literature databases including CNKI,Wan Fang,VIP,PubMed,EMbase,and Cochrane Library,were systematically searched,according to the inclusion and exclusion criteria. Review Manager 5.3 software was used to input the literatures,and we assessed the risk bias on the level of outcome indicators for each included literature. A total of 18 literatures were included,and the classification results showed that: compared with MTX,TGT alone can reduce the number of joint swelling( MD =0. 18,95%CI[-1.06,1.42],P = 0.78) and joint tenderness( MD =-0.06,95% CI[-1.69,1.56],P = 0.94) in RA patients with the same effect as MTX. In terms of drug combination,TGT combined with MTX had an advantage over MTX alone in lessening the morning stiffness time( MD = 18. 24,95% CI[12. 64,23. 84],P < 0. 000 01) of RA,joint tenderness( MD = 2. 65,95% CI[1. 85,3. 44],P<0.000 01) and joint swelling( MD = 3.01,95% CI[2.09,3.39],P< 0.000 01). In conclusion,this Meta-analysis suggest that TGT alone was superior to MTX in improving joint swelling and tenderness in RA patients,TGT combined with MTX may improve the clinical manifestation of RA patients better than MTX alone.
Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Glycosides ; therapeutic use ; Humans ; Methotrexate ; therapeutic use ; Tablets ; Treatment Outcome ; Tripterygium ; chemistry