Rheumatoid arthritis (RA) causes serious disability and productivity loss, and there is an urgent need for appropriate biomarkers for diagnosis, treatment assessment, and prognosis evaluation. To identify serum markers of RA, we performed mass spectrometry (MS)-based proteomics, and we obtained 24 important markers in normal and RA patient samples using a random forest machine learning model and 11 protein–protein interaction (PPI) network topological analysis methods. Markers were reanalyzed using additional proteomics datasets, immune infiltration status, tissue specificity, subcellular localization, correlation analysis with disease activity-based diagnostic indications, and diagnostic receiver-operating characteristic analysis. We discovered that ORM1 in serum is significantly differentially expressed in normal and RA patient samples, which is positively correlated with disease activity, and is closely related to CD56dim natural killer cell, effector memory CD8⁺T cell, and natural killer cell in the pathological mechanism, which can be better utilized for future research on RA. This study supplies a comprehensive strategy for discovering potential serum biomarkers of RA and provides a different perspective for comprehending the pathological mechanism of RA, identifying potential therapeutic targets, and disease management.

It is still a clinical challenge to sustain the remission of rheumatoid arthritis (RA); thus, identifying more effective and safer agents for RA treatment remains an urgent demand. We investigated the anti-arthritic activity and potential mechanism of action of sodium Danshensu (SDSS), a structurally representative water-soluble derivative of Danshen, on collagen-induced arthritis (CIA) mice. Our results showed that paw edema, synovium hyperplasia, bone destruction, and the serum levels of both IL-1β and IL-6 were ameliorated by SDSS (40 mg/kg·d) in CIA mice. In addition, there was no difference between SDSS and methotrexate (MTX, 2 mg/kg·3d) treatment in the above indicators. Further mechanism studies illustrated that SDSS inhibited IL-1β secretion by downregulating the HIF-1α/STAT3/NLRP3 pathway in macrophages. On the other hand, HIF-1α accumulation and HIF-1α/STAT3/NLRP3 pathway activation by IOX4 stimulation reduced the therapeutic effect of SDSS. These findings demonstrate that SDSS displays anti-arthritic activity in CIA mice and prevents proinflammatory cytokines secretion in macrophages by suppressing the HIF-1α/STAT3/NLRP3 pathway.

Background: Yishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear.Purpose and study design: The purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS).Results: The findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-β (TGF-β). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated.Conclusion: Taken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.

Yishen Tongbi decoction (YSTB) which is an herbal formula, has been used for the treatment of rheumatoid arthritis (RA) for more than ten years with a better curative effect. Methotrexate (MTX) is an effective anchoring agent used to treat rheumatoid arthritis. There were, however, no head-to-head comparative randomized controlled trials comparing traditional Chinese medicine (TCM) to MTX, Therefore, we performed this double-blind, double-model, randomized controlled trial of the efficacy and safety of YSTB and MTX in the treatment of active RA for 24 weeks. Patients who met the enrollment criteria were randomly selected (1:1) to receive either YSTB therapy (YSTB 150 ml once daily + MTX placebo 7.5-15 mg once weekly) or MTX therapy (MTX 7.5-15 mg once weekly + YSTB placebo 150 ml once daily) in treatment cycles lasting 24 weeks. The percentage of patients who achieve a clinical disease activity index (CDAI) response at week 24 is the primary efficacy outcome. A 10% risk differential non-inferiority margin was previously defined. The Chinese Clinical Trials Registry has recorded this trial (ChiCTR-1,900,024,902, registered on August 3rd 2019, http://www.chictr.org.cn/index.aspx). Out of 118 patients whose eligibility was determined from September 2019 to May 2022, 100 patients (n = 50 for each group) were enrolled in the research overall. The 24-week trial was completed by 82% (40/49) of the YSTB group's patients and 86% (42/49) of the MTX group's patients. In the intention-to-treat analysis, 67.4% (33/49) of patients in the YSTB group met the main outcome of CDAI response criteria at week 24, compared to 57.1% (28/49) in the MTX group. The risk difference was 0.102 (95% CI -0.089 to 0.293), which demonstrated the non-inferiority of YSTB to MTX. After further testing for superiority, the ratio of CDAI responses achieved by the YSTB and MTX groups was not statistically significant (p = 0.298). At the same time, in week 24, secondary outcomes such as the ACR 20/50/70 response, the European Alliance of Associations for Rheumatology good or moderate response, remission rate, simplified disease activity index response, and low disease activity rate all showed similar statistically significant patterns. There was statistically significant attainment of ACR20 (p = 0.008) and EULAR good or moderate response (p = 0.009) in two groups at week 4. The intention-to-treat analysis results and the per-protocol analysis results were in agreement. The incidence of drug-related adverse events was not statistically different between the two groups (p = 0.487). Previous studies have used TCM as an adjunct to conventional therapy, and few of them have directly compared it with MTX. In order to lessen disease activity in RA patients, this trial demonstrated that YSTB compound monotherapy was non-inferior to MTX monotherapy and had superior efficacy following short-term treatment. This study provided evidence-based medicine in the treatment of RA with compound prescriptions of TCM and contributed to promoting phytomedicine use in RA patients.

Objectives Diet has been shown to be associated with rheumatoid arthritis (RA), and magnesium has been shown to inhibit inflammatory responses, but research on the relationship between dietary magnesium and RA is limited and controversial. In this study, we aimed to explore the non-linear relationship between dietary magnesium intake and RA in US women. Design Cross-sectional survey. Setting National Health and Nutrition Examination Survey (NHANES). Primary and secondary outcome measures Non-linear relationship between dietary magnesium intake and prevalence of RA. Participants A total of 13 324 women aged 18–80 years (RA n=12 306, non-RA n=1018) were included in this study. Results Overall, the absolute risk (AR) of RA was 7.24% in all participants. In the multivariable logistic regression analysis, we found a negative correlation between dietary magnesium intake and RA (OR=0.84, 95% CI 0.75 to 0.95, p=0.006). When we converted dietary magnesium intake into a categorical variable (tertiles), the ARs of the low group, the middle group and the high group were 9%, 7.1% and 4.9%, respectively. We noticed that the ORs between the three groups were not equidistant; then, we detected a U-shaped linking by smooth curve fitting and obtained inflection points at 181 and 446 mg/day. The prevalence of RA decreased when dietary magnesium intake was <181 mg/day (OR=0.7, 95% CI 0.5 to 0.8, p446 mg/day (OR=2.8, 95% CI 1.2 to 6.6, p=0.020), remaining at a minimum when it was between 181 and 446 mg/day (OR=1.0, 95% CI 0.7 to 1.2, p=0.700). Conclusion There was a U-shaped relationship between dietary magnesium and RA in women, and our study highlights the importance of moderate dietary magnesium intake in possibly exerting a protective role in women with RA.