Efficacy and safety of progressively reducing biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis in persistent remission: a study protocol for a non-inferiority randomized, controlled, single-blind trial.

BACKGROUND: To compare the effects of two biologic disease-modifying antirheumatic drug (bDMARD) administration strategies on the maintenance effect and safety of patients with rheumatoid arthritis (RA) in remission, to analyze the effects of gradual drug reduction and dose maintenance treatment on clinical outcomes in patients who have achieved remission with different types of bDMARDs, to search and screen out people who may benefit from drug reduction strategies, and to provide references for drug reduction strategies and treatment options for patients with RA in remission, so as to help improve the safety of the treatment and reduce the economic burden. METHODS: The study will be a 24-month non-inferiority randomized, controlled, single-blind trial and is planned to be launched in our hospital from September 2021 to August 2023. Patients will be randomized in a ratio of 2:1 to two groups: maintenance or injection spacing by 50%/gradual reduction of dosage every 3 months up to complete stop. When the patient relapses, return to the last effective dose. If the remission can be maintained, the medication of bDMARDs can be stopped 9 months after enrollment. The primary outcome will be the persistent flare rate. DISCUSSION: Our study may provide a reference for the selection of drug reduction strategies and treatment options for patients with RA in remission, so as to help improve the safety of the treatment and reduce the economic burden. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100044751. Registered on 26 March 2021.

Upregulation of miR-27b Facilitates Apoptosis of TNF-α-Stimulated Fibroblast-Like Synoviocytes.

PURPOSE: The aim of this study was to explore the function of microRNA-27b (miR-27b) in fibroblast-like synoviocytes (FLSs) stimulated by tumor necrosis factor α (TNF-α). MATERIALS AND METHODS: mRNA expression of miR-27b in FLS cells (MH7A) treated with or without TNF-α was determined by q-PCR. MiR-27b mimics was transfected into MH7A cells to upregulate miR-27b expression. MTT assay and flow cytometry analysis were performed to investigate the effect of miR-27b on MH7A cell viability and apoptosis. The targets of miR-27b were predicted by TargetScan. The direct regulation of miR-27b on IL-1ß expression was verified by luciferase assay. The protein expression levels of apoptosis-related proteins, IL-1ß, and NF-κB signaling-related proteins were detected by Western blot. RESULTS: We discovered that miR-27b expression was decreased in MH7A cells stimulated by TNF-α. Upregulation of miR-27b by miR-27b mimics significantly inhibited the proliferation and promoted the apoptosis of TNF-α-stimulated MH7A cells. Consistently, upregulation of miR-27 decreased the level of Bcl-2 and increased Bax and caspase-3 expression in MH7A cells stimulated by TNF-α. Luciferase assay revealed that IL-1ß was indeed a target of miR-27b. By quantitative real-time PCR and Western blot, we found that the expression of IL-1ß is negatively regulated by miR-27b. Moreover, the NF-κB signaling pathway was significantly inhibited by miR-27b. CONCLUSION: Taken together, our results illustrated that enhanced miR-27b expression results in the suppression of proliferation and the promotion of apoptosis in FLSs stimulated by TNF-α, partially by regulating IL-1ß expression and NF-κB signaling.

Correlations between TLR polymorphisms and inflammatory bowel disease: a meta-analysis of 49 case-control studies.

Recently, the roles of toll-like receptor (TLR) polymorphisms in inflammatory bowel disease (IBD) were intensively explored, with conflicting results. Therefore, we performed this study to better assess the relationship between TLR polymorphisms and the risk of IBD. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate associations between TLR polymorphisms and IBD. Significant associations with the risk of IBD were detected for the TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, and TLR6 rs5743810 polymorphisms in overall analyses. Further subgroup analyses according to ethnicity of participants revealed that the TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810, and TLR9 rs352140 polymorphisms were significantly associated with the risk of IBD in Caucasians. Moreover, the TLR4 rs4986790 polymorphism was significantly correlated with the risk of IBD in West Asians, while the TLR9 rs352140 polymorphism was significantly associated with the risk of IBD in Africans. When we stratified available data according to type of disease, we found similar positive results for TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, and TLR6 rs5743810 polymorphisms. Our findings indicate that TLR1 rs5743611, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810, and TLR9 rs352140 polymorphisms may serve as genetic biomarkers of IBD in certain ethnicities. However, further well-designed studies are still warranted to confirm our findings.

[Efficacy Observation of Chinese Herbal Fumigation Combined Western Drugs for Treating Sys- temic Sclerosis Complicated Pulmonary Arterial Hypertension].

Objective To observe the therapeutic efficacy and safety of Chinese herbal fumigation combined with leflunomide (LEF) and prednisone (Pred) in treatment of systemic sclerosis (SSc) complicated pulmonary arterial hypertension (PAH). Methods Totally 99 SSc patients complicated early PAH were randomly assigned to the Western drugs group (WD, 49 cases) and the integrative medicine group (IM, 50 cases). Patients in the WD group took LEF (20 mg) and Pred (15 mg) , once per day. In addition to routine WD program, those in the IM group additionally received Chinese herbal fumigation. All treatment lasted for 6 months. Raynaud's phenomenon (RP) was observed in each group before and after treatment. RP score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), pulmonary arterial systolic pressure (PASP) , and pulmonary function were compared between the two groups before and after treatment. The clinical efficacy and adverse reactions were evaluated. Results Thirteen cases were lost due to various reasons. A total of 86 patients completed this study, 41 in the WD group and 45 in the IM group. Compared with the same group before treatment, RP score, levels of ESR and CRP all decreased in the two groups after treatment (P <0. 05). Compared with the WM group after treatment, RP score, levels of ESR and CRP were obviously lowered in the IM group after treatment (P < 0. 05). Besides, lowered differences between post-pre-values of ESR, CRP, and PASP were more obviously higher, while elevated differences between post-pre-values of total lung capacity (TLC) and carbon monoxide diffusing capacity (DLCO) were more obviously higher in the IM group (P <0. 05). The total effective rate was 93. 33% (42/45) in the IM group, obviously higher than that in the WD group [70. 73% (29/41) , P <0. 05 ]. There was no statistical difference in total adverse reaction rate between the two groups (x² =0. 019, P =0. 891). Conclusion Chinese herbal fumigation combined with WD had obvious efficacy with less adverse reactions, so it was worth clinical spread.