IMPORTANCE: Digital health applications have been shown to be effective in the management of chronic diseases with simple treatment targets. The potential clinical value of digital health applications in rheumatoid arthritis (RA) has not been well studied.OBJECTIVE: To investigate whether assessing patient-reported outcomes using digital health applications could result in disease control for patients with RA.DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, open-label randomized clinical trial in 22 tertiary hospitals across China. Eligible participants were adult patients with RA. Participants were enrolled from November 1, 2018, to May 28, 2019, with a 12-month follow-up. The statisticians and rheumatologists who assessed disease activity were blinded. Investigators and participants were not blind to group assignment. Analysis was conducted from October 2020 to May 2022.INTERVENTIONS: Participants were randomly assigned at a 1:1 ratio (block size of 4) to a smart system of disease management group (SSDM) or a conventional care control group. Upon the completion of the 6-month parallel comparison, patients in the conventional care control group were instructed to use the SSDM application for an extension of 6 months.MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of patients with disease activity score in 28 joints using the C-reactive protein (DAS28-CRP) of 3.2 or less at month 6.RESULTS: Of 3374 participants screened, 2204 were randomized, and 2197 patients with RA (mean [SD] age, 50.5 [12.4] years; 1812 [82.5%] female) were enrolled. The study included 1099 participants in the SSDM group and 1098 participants in the control group. At month 6, the rate of patients with DAS28-CRP of 3.2 or less was 71.0% (780 of 1099 patients) in the SSDM group vs 64.5% (708 of 1098 patients) in the control group (difference between groups, 6.6%; 95% CI, 2.7% to 10.4%; P = .001). At month 12, the rate of patients with DAS28-CRP of 3.2 or less in the control group increased to a level (77.7%) that was comparable with that (78,2%) in the SSDM group (difference between groups, −0.2%; 95% CI, −3.9% to 3.4%; P = .90).CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of RA, the use of a digital health application with patient-reported outcomes was associated with an increase in disease control rate.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03715595

Objective. To explore the underlying mechanism of the sonic hedgehog (Shh) signaling pathway in promoting cell proliferation and migration in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Method. FLS were collected from 8 patients with RA and 3 patients with osteoarthritis (OA). The expression of smoothened (Smo, the Shh pathway activator) was quantified by real-time PCR and western blot. FLS were incubated with cyclopamine (a Smo antagonist), purmorphamine (a Smo agonist), Y27632 (a Rho/ROCK signaling inhibitor), or a combination of purmorphamine and Y27632, respectively. Cell proliferation was examined using cell counting kit-8 and cell cycle assays while cell migration was measured with Transwell and wound healing assays. Results. The expression of Smo was higher in FLS from RA patients than from OA patients ( ). RA-FLS treated with purmorphamine showed significantly activated proliferation (119.69 vs. 100.0) and migration (252.38 vs. 178.57) compared to untreated cells (both ). RA-FLS incubated with cyclopamine or a combination of purmorphamine and Y27632 exhibited significant suppression of proliferation (81.55 vs. 100.0 and 85.84 vs. 100.0) and migration (100 vs. 178.57 and 109.52 vs. 185) ability (all ). Conclusion. Our results demonstrated that Shh promoted cell growth and migration of FLS in RA patients through the Rho/ROCK signaling pathway.

The coronavirus disease 2019 (COVID-19) pandemic has imposed enormous morbidity and mortality burdens. Patients with rheumatic diseases (RDs) are vulnerable to the COVID-19 infection, given their immunocompromised status. Ensuring acceptance of the COVID-19 vaccine is important and has attracted attention by health professionals. In this study, we designed an online cross-sectional survey that used an online questionnaire from 8 May 2021 to 4 October 2021. Attitudes toward the COVID-19 vaccination, personal information, current disease activity status, adverse events (AEs), and knowledge sources of vaccines were collected. Descriptive statistics, nonparametric tests, and ordinal logistic regression were used to analyze the data. A total of 1022 questionnaires were received, among which 70.2% (720/1022) of patients with RDs agreed to vaccination, while only 31.6% of patients were actually vaccinated. Male, employed, high-income patients and those with inactive disease showed a more positive attitude. Concerns of AEs and disease flare were the main factors affecting vaccination willingness. Only 29.6% (304/1022) of patients thought they had received enough information about the COVID-19 vaccine from their doctors. In conclusion, most patients with RDs in China intended to get vaccinated, although the vaccination rate in this particular population was low. Rheumatologists should take more responsibility in COVID-19 vaccination education of patients with RDs.

Hyperuricemia and its complications, including gouty arthritis and hyperuricemic nephropathy, are driven by elevated serum urate levels and crystal deposition. While exogenous uricase offers therapeutic potential, its utility is limited by rapid clearance and immunogenicity. Here we show a malic acid-derived lipid nanoparticle platform with antioxidant and low-immunogenicity properties for delivering circular RNA encoding secretory uricase to treat hyperuricemia and its complications. Leveraging the safety and anti-inflammatory and antioxidant properties of malic acid, a combinatorial library of ionizable lipids is developed. After systematic screening and optimization, LMA2-C10 LNPs are selected to deliver circRNA for its high transfection efficiency, low-immunogenicity, and antioxidant activity. In male animal models, the system achieves sustained urate reduction, attenuation of tissue inflammation and fibrosis, alleviation of arthritic pain, and preservation of renal function. This integrated strategy simultaneously addresses hepatic urate catabolism, peripheral crystal clearance, and long-lasting pharmacological activity, presenting an alternative strategy to resolve the core challenges in hyperuricemia management.

Purpose: This study aimed to compare the rates of disease remission evaluated using various remission criteria, including Boolean2.0, Boolean1.0, clinical disease activity index (CDAI), simplified disease activity index (SDAI), and disease activity score using 28 joints based on C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA). Patients and Methods: A cross-sectional observational analysis was performed using data from patients with RA enrolled in a smart system of disease management group (SSDM). The clinical remission rates of RA patients estimated using the DAS28-CRP, CDAI, SDAI, Boolean1.0 and Boolean2.0 criteria were investigated. Variables were compared using the t-test, Mann–Whitney U-test, or chi-squared test. The agreement between Boolean remission and the DAS28-CRP, CDAI, or SDAI definitions of remission was assessed using McNemar’s test with k coefficient of agreement. Results: A total of 5619 patients were included in the analysis. The mean age of the patients was 56.33 (± 13.01) years, with the majority being female (4491, 79.9%). The rates of remission, as assessed by Boolean2.0, Boolean1.0, DAS28-CRP, CDAI, and SDAI, were 16.6%, 9.7%, 35.2%, 9.1%, and 9.4%, respectively. Comparison with Boolean1.0 criteria revealed higher concordance between Boolean2.0 and DAS28-CRP remission and lower concordance with CDAI and SDAI, regardless of whether the analysis was conducted on the entire population or subgroups based on gender, age or disease duration. Additionally, the administration of different medications may have influenced the rate of Boolean2.0 remission. Conclusion: This study demonstrated a higher concordance between Boolean2.0 criteria and DAS28-CRP remission and a lower concordance with CDAI and SDAI when compared with Boolean1.0 remission criteria.