Objective To study the expression of peripheral blood lymphocyte P-glycoprotein(P-gp)and related impact factors in rheumatoid arthritis(RA)patients,and explore whether the periodic combination of methotrexate(MTX)or leflunomide(LEF)with cyclophosphamide(CTX)could reverse P-gpinduced drug resistance.Methods This study was a cross-sectional study.Forty-two RA patients were enrolled(15 cases in the primary untreatment group,while 27 cases in the treatment group).In the treatment group,patients were divided into the improvement group(12 patients)and the refractory group(15 patients)respectively according to their disease activity scores(DAS 28).According to the medication used,42 patients were divided into 3 groups:the monotherapy group(MTX or LEF),the MTX+LEF combination treatment group and MTX or LEF+CTX treatment group.The expression of peripheral blood lymphocyte P-gp in each group was detected by flow cytometry.T test,ANOVA,LSD test,Bonferroni test,x2 test and Pearson correlation analysis were used for statistical analysis with software 13.0.Results ① Mean relative fluore scence intensity(RFI)of P-gp was 2.0±0.7,2.9±1.0,3.5±1.4,5.0±2.0 respectively in healthy control group,the primary untreatment group,the improvement group and the refractory group,the difference was significant(F=7.955,P＜0.01).in multiple comparisons,the fluorescence intensity was higher in the primary untrea-tment group as compared to the healthy group,but the difference was not statistically significant(P=0.137);however,it was significantly higher in the refractory group as compared to the improvement group(P=0.013).② There was no correlation between the expression of P-gp in RA patients and sex,age of onset,disease duration or positive rate of RF.But the expression of P-gp was significantly correlated with ESR and DAS28(r=0.447,P=0.002;r=0.398,P=0.012).③ RFI of the P-gp group was 5.1±2.2,6.0±1.2,3.4±1.1 respectively in monotherapy group,MTX+LEF group and MTX/LEF+ CTX group(P＜0.05).The expression of P-gp was significantly lower in the MTX/LEF+CTX group as compared to the monotherapy group(P＜0.05),but higher in the MTX+LEF group(P＞0.05).Conclusion The expression of peripheral blood lymphocyte P-gp in RA is correlated with disease activity.The loss of efficacy in DMARDs is due to the enhanced expression of P-gp.Combination of methotrexate or leflunomide with cyclo-phosphamide reverses P-glycoproteininduced drug resistance.

Recently, a novel atypical porcine pestivirus (APPV) in pig was reported. In this study, two APPV strains, APPV-China/GZ01/2016 (GZ01) and APPV-China/GD-SD/2016 (GD-SD), were identified in two newborn piglet herds with congenital tremor from China. The open reading frame of the two strains shared an 83.5% nucleotide identity. Phylogenetically, the APPV strains were placed into two groups: GZ01 belonged to group I and GD-SD belonged to group II. A high viral load was detected in the cerebellum (quantification cycles < 26). Further studies should be carried out to thoroughly elucidate the development of congenital tremors caused by APPV.
Cerebellum ; China ; Genome ; Humans ; Infant, Newborn ; Open Reading Frames ; Pestivirus ; Tremor ; Viral Load

Objective:To investigate the characteristics of lymphocyte subsets and the correlation between the immune imbalance of T helper 17 cell/regulatory T cell (Th17/Treg) and cytokines in peripheral blood of patients with Beh?et's disease(BD).Methods:From January 2018 to November 2019, 82 outpatient and inpatient with BD of the Department of Rheumatology and Immunology of the Second Hospital of Shanxi Medical University with complete data were enrolled. The disease activity was evaluated according to BD Current Activity Form(BDCAF), and 66 age and matched healthy people were selected as the control group. The absolute numbers of lymphocyte subsets and T cell subsets dominated by Th17 and CD4 +CD25 +Foxp3 + Treg in patients with BD and healthy controls were detected by Flow cytometry. The levels of interleukin (IL-2), IL-4, IL-6, IL-10, IL-17, Interferon (IFN)-γ and Tumor necrosis factor-α (TNF)-α in patients with BD were measured by Cytometric Beads Array (CBA). The correlations between the ratio of Th17/Treg with inflammatory index, the number of organ involved and the levels of cytokines were analyzed. Data were analyzed by Mann-Whitney U test, Kruskal Wallis H test, Spearman correlation analysis and multiple linear regression. Results:①The absolute numbers of Th17 cells in peripheral blood of patients with active BD [13.9(7.7, 21.1) cells/μl] and patients with stable BD [8.7(6.1, 14.0) cells/μl] were higher than those of healthy controls [6.8(4.4, 8.5) cells/μl] ( P<0.01); The ratio of Th17/Treg was significantly increased ( P<0.01). The absolute co unts of Treg cells in BD group [24.79(15.64, 37.91) cells/μl] were sign-ificantly lower than those in healthy controls [30.59(23.04, 42.08) cells/μl], the difference was statistically significant ( P=0.016). ② The ratio of Th17/Treg was positively correlated with BDCAF ( r=0.298, P=0.007) and the number of organ involved ( r=0.304, P=0.006) was negatively correlated with age ( r=-0.254, P<0.05), and not correlated with the duration of disease and ESR ( P>0.05) in patients with BD. In addition, multiple linear stepwise regression showed that the ratio of Th17/Treg was positively correlated with BDCAF ( β=0.228, P=0.036) and negatively correlated with age ( β=-0.219, P=0.043), R2=0.101. ③ The levels of IL-2, IL-6, IL-10, IFN-γ in patients with BD were stati-stically higher than those of healthy controls ( P<0.01). The ratio of Th17/Treg was positively correlated with the levels of IL-2 ( r=0.307, P<0.01) and IL-4 ( r=0.301, P<0.01) in patients with BD. Conclusion:There is immune imbalance of Th17/Treg in patients with BD, which is closely related to disease activity, the number of organ involved, and the levels of cytokines such as IL-2 and IL-4. IL-2 and IL-4 may play an important role in the immune imbal-ance of Th17/Treg in patients with BD.

ObjectiveTo examine the clinical features of fractures and related risk factors in patients with rheumatoid arthritis(RA) in China.MethodsSix hundred and eighty-one RA patients were randomly selected from department of rheumatology of 18 hospitals of China.Data were obtained from the questionnaire,including age,sex,disease duration,the involvement of joints,treatment regimen,features of fractures etc.The possible risk factors of fracture in patients with RA were analyzed with a multi-variate Logistic regression analysis.Results① In 681 RA patients of the survey,48 patients had 54 fractures,and the incidence of fractures was about 8％.② Fractures occurred at various sites.Foot/ankle,femur,spine and wrist were the mostfrequent sites.③ The Logistic regression analysis showed that several factors increased the risk of fracture in RA patients,including long disease duration (OR:1.245,95％CI:0.987-1.570,P=0.065),male gender(OR:0.433,95％CI:0.199-0.942,P=0.035),more deformed joints(OR:1.042,95％CI:1.006-1.079,P=0.023),family history of RA (OR:2.201,95％CI:0.984-4.923,P=0.055),and high scores of SF-36(OR:1.017,95％CI:1.002-1.033,P=0.028).④ According to the degree of correlation from strong to weak,the risk factors of fracture were disease duration,SF-36,sex,number of deformed joints and family history of rheumatoid arthritis.ConclusionThe incidence of fracture is high in patients with rheumatoid arthritis.Several factors could increase the risk of fractures in RA patients,including long disease duration,male gender,more deformed joints,and family history of RA.In order to prevent the occurrence of fractures,cautions should be taken to prevent the development of fractures and treat the disease aggressively to suppress the disease activity of RA.