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Background: Sjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells and inflammatory factors. Despite increased researches and studies recently focusing on this area, it remains to be fully elucidated. We decide to incorporate genetic insight into investigation of the causal link between various immune cells, inflammatory factors and pathogenesis of Sjogren syndrome (SS). Methods: Our study leveraged the genetic variants of multi-omics statistics extracted from genome-wide association study (GWAS), the University of Bristol and the FinnGen study. We performed a bidirectional Mendelian randomization and mediation study based on randomly allocated instrumental variables to infer causality, followed by external validation with UK Biobank data and Bayesian colocalization. Results: We demonstrated that an elevated level of CD27 on IgD + CD24 + B cell, a subset of B cells expressing both IgD and CD24, was associated with a higher risk of SS (OR = 1.119, 95% CI: 1.061–1.179, P < 0.001), while CD3 on CD45RA + CD4 + Treg was a protective factor (OR = 0.917, 95%CI: 0.877–0.959, P < 0.001). Results of meta-analysis and colocalization further supported the significant results identified in the primary analysis. A total of 4 inflammatory cytokines and 7 circulating proteins exhibited potential causal relationships with SS despite no significant result achieved after FDR correction. Finally, results of mediation analysis indicated that CD40L receptor levels had significant mediating effects (β = 0.0314, 95% CI: 0.0004–0.0624, P = 0.0471) at a mediation proportion of 28% (95% CI: 0.364%-55.6%) in causal relationship between CD27 on IgD + CD24 + B cell and SS. Conclusions: By providing a novel genetic insight into unveiling the roles of autoimmunity and inflammation in Sjogren syndrome, our findings may potentially lead to identifying new clinical biomarkers for disease monitoring and therapeutic targets that offer more effective alternatives for treating this condition. Therefore, our study may provide valuable evidence for future clinical intervention and targeted immunotherapy. [ABSTRACT FROM AUTHOR]

Ultrasound can activate nano/microparticles to induce reactive oxygen species (ROS). The advantages of deep penetration and precise spatiotemporal control are demonstrated for multiple applications, such as sonodynamic therapy, chemical industry, and environmental treatment. Meanwhile, a toolbox of inorganic particles is developed to enhance ROS production via cavitation enhancement, sonoluminescence, and piezocatalytic effect. Nonetheless, sophisticated influences of ultrasonic parameters hamper further exploration of novel sonosensitized materials. In this perspective, the influential parameters in different mechanisms are reviewed, emphasizing the relationship between ultrasound frequency and catalytic activity, and outlooks are provided on the study of inorganic sonosensitizers. [ABSTRACT FROM AUTHOR]

Vitamin D binding protein (VDBP) is a potential biomarker of major depressive disorder (MDD). This study demonstrates for the first time that VDBP is highly expressed in core emotion-related brain regions of mice susceptible to chronic unpredictable mild stress (CUMS). Specifically, the overexpression of microglia (MG)-derived VDBP in the prelimbic leads to depression-like behavior and aggravates CUMS-induced depressive phenotypes in mice, whereas conditional knockout of MG-derived VDBP can reverse both neuronal damage and depression-like behaviors. Mechanistically, the binding of MG-derived VDBP with the neuronal receptor megalin mediates the downstream SRC signaling pathway, leading to neuronal and synaptic damage and depression-like behaviors. These events may be caused by biased activation of inhibitory neurons and excitatory-inhibitory imbalance. Importantly, this study has effectively identified MG-derived VDBP as a pivotal mediator in the interplay between microglia and neurons via its interaction with the neuronal receptor megalin and intricate downstream impacts on neuronal functions, thus offering a promising therapeutic target for MDD., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: To investigate the current status of methotrexate (MTX) application in rheumatoid arthritis (RA) patients., Methods: The clinical and laboratory data of RA patients who attended in the Department of Rheumatology and Immunology of Peking University Third Hospital from January 1, 2022 to November 31, 2023 were collected retrospectively. In order to figure out the relationship between MTX use and RA disease control, we recorded information including the starting dose, maximum dose, current dose, reasons of discontinuation of MTX, etc . The t test, Mann-Whitney U test, Chi-square test, Fisher' s exact probability and multivariable Logistic regression were used for analysis., Results: A total of 239 RA patients were enrolled, including 201 females and 38 males with a mean age of (54.5±14.3) years. Among them, 101 patients reached the therapeutic target [clinical remission or low disease activity assessed by 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR)], accounting for 42.2% of the RA patients. Twenty-six patients met the European League Against Rheumatism (EULAR) definition of difficult-to-treat (D2T) RA, accounting for 10.9% of RA patients. The proportion of the RA patients who had ever used MTX was 84. 1%, and those who were currently on it accounted for only 39.7%. The MTX dose was generally low, with a starting dose of (9.5±3.0) mg/week, the maximum dose of 15.0 (10.0, 15.0) mg/week, and the current dose being (12.4±2.7) mg/week. The most common reasons for MTX dose reduction or discontinuation were adverse reactions, mainly including abnormalities of hepatic function, gastrointestinal discomfort, leucopenia, etc. Those who were currently on MTX had a higher rate of treatment to target (52.6% vs. 35.4%, P> 0.05), lower disease activity score (DAS28-ESR, 3.6±1.8 vs. 4.2±1.8, P < 0.05), and fewer tender joint counts (4.8±8.3 vs. 8.6±10.4, P < 0.05) as compared with those who were not taking the drug, while swollen joint count, pain visual analog score and patient' s global score, C-reactive protein (CRP) level and ESR level were not significantly different between the two groups. Compared with those who did not reach the target of treatment, those who did had a higher rate of current MTX application (48.5% vs. 33.3%, P < 0.05), but the history of MTX did not differ between the two groups (84.2% vs. 84.1%, P >0.05). The maximum dose of MTX (median 15.0 mg/week vs. 13.7 mg/week, P >0.05) and the current dose [(12.9±2.5) mg/week vs. (11.8±2.8) mg/week, P >0.05] was higher in those who achieved the target, while the starting dose [(9.6±2.8) mg/week vs. (9.5±3.1) mg/week, P >0.05] and the rate of prior MTX (84.2% vs. 83.3%, P >0.05) was comparable between the two groups. The D2T RA patients had a higher rate of previous MTX use (96.2% vs. 82.6%, P < 0.05) and a higher starting dose [(11.6±4.3) mg/week vs. (9.8±2.7) mg/week, P >0.05], while the maximum dose (median 12.5 mg/week vs. 15.0 mg/week, P >0.05) and the current dose were both lower [(11.6±3.2) mg/week vs. (12.5±2.6) mg/week, P >0.05] than the non-D2T RA patients., Conclusion: The proportion of regular use of MTX among RA patients was low and the dose was generally small. The RA patients with regular use of MTX had a higher rate of achieving treatment target and lower disease activity. Those who achieved the target had a higher rate of current MTX use, higher maximum and current doses than those who did not. The D2T RA patients had lower maximum and current doses of MTX than the non-D2T RA patients. Therefore, increasing the usage and dosage of MTX in RA patients may help to improve the rate of achieving treatment targets.