Efficacy of tacrolimus combined with methotrezate in the treatment of patients with refractory rheumatoid arthritis / 中华风湿病学杂志

Objective To assess the efficacy and safety of tacrolimus (TAC) combined with methotrexate (MTX) for the treatment of refractory rheumatoid arthritis (RA),and to compare it with cyclophosphamide (CTX) added to MTX for the treatment of refractory RA.Methods Thirty-six cases of refractory RA patients were divided into the observation group and the control group.TAC+MTX were used in the observation group,and CTX+MTX were used in the control group.We used repeated measures to analyze the variance and Fisher exact probability method to analyze the efficacy at 8 weeks and 24 weeks.Results The effective rate of the observation group in 8 weeks,24 weeks were 77.8％(14 cases) and 100％(18 cases) respectively,while those of the control group were 11.1％ (2 cases) and 44.4％(8 cases),it showed that both TAC+MTX and CTX+MTX in the treatment of refractory RA were effective,but the efficacy of TAC+MTX was better than CTX+MTX,the difference of C reactive protein (CRP) and disease activity score (DAS)28 was statistically significant (P＜0.05),and it could significantly improve the clinical symptoms and laboratory indexes.Conclusion TAC+MTX is effective and safe in treating refractory RA,and is worth of spreading.

Study on Foxp3 promoter region methylation of mononuclear cells in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective By detecting the expression levels of Foxp3 in CD4+CD25+ regulatory T cells of peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA),and the Foxp3 gene promoter region methylation to explore its role in the pathogenesis of RA.Methods Twenty-five RA patients and 10 healthy controls were selected,and the PBMCs were extracted by density gradient centrifugation.Foxp3 expression levels of CD4+CD25+ regulatory T cells were detected by flow cytometry.The real-time fluorescence quantitative PCR assay was used to detect the Foxp3 mRNA expression in PBMCs; and bisulfate processing gene sequencing was used to determinethe differences in Foxp3 gene promoter sequence methylation level of PBMCs.The comparison between groups was analyzed using one-way ANOVA; two sets of qualitative data were compared using Fisher's exact test.Results The expression levels of Foxp3 mRNA in the CD4+CD25+regulatory T cells of active RA patients (2.31±0.25) was significantly lower than inactive RA group (3.68±0.26) and healthy controls (5.67±0.34),the difference was statistically significant (P＜0.05).The Foxp3 mRNA expression level in inactive RA group was lower than that of the healthy controls (P＜0.05).Foxp3 promoter region-67,-74 sites of methylation level in PBMCs of RA patients (46％) was significantly higher than that of the healthy controls (6％).Conclusion Reduction in the number of CD4+CD25+ regulatory T cells may be involved in the pathogenesis of RA and Foxp3 gene promoter methylation levels plays a key role in this process.

The expression of proline-rich tyrosine kinase and its role in systemic lupus erythematosus / 中华风湿病学杂志

Objective To explore the possible role of proline-rich tyrosine kinase (Pyk2) in the pathogenesis of systemic lupus erythematosus (SLE).Methods The expression of Pyk2 in the peripheral blood mononuclear cells (PBMCs) of 50 patients with SLE and 36 healthy controls were tested with RT-PCR assay.The activation of Pyk2 was inhibited using specific inhibitor Pyk2 (TyrA9).Semi-quantitative PCR methodwas used to detect the Blys expression of PBMCs.One-way ANOVA and Pearson's correlation analysis were used for statistical analysis.Results The Pyk2 expression level (28.31 ±0.91) of SLE patients was significantly higher than that in healthy controls (33.69±0.04),the difference was statistically significant (P＜0.05).The activation of Pyk2 was stimulated and the expression levels of Blys in the PBMCs of patients with SLE was elevated.By inhibiting the activation of Pyk2,the BLyS expression levels decreased significantly.Conclusion Pyk2 may be involved in the abnormal activation of lymphocytes which lead to the pathogenesis of SLE.Pyk2 expression is associated with SLE disease activity,disease aggravation,and the Pyk2 expression levels is also increased significantly.In addition,the expression level of Pyk2 is higher in patients with renal involvement than those patients with other organ involvement.