Tongji Hospital

Despite advances in anthelmintic therapy, there are currently no effective treatments for schistosomiasis-induced liver fibrosis. Previous studies have reported elevated marginal zone B and B1 cell specific protein (MZB1) expression in fibrotic diseases, but its function remains unclear, and its role in schistosomiasis has not been investigated. This study aimed to explore the function and mechanism of MZB1 in Schistosoma japonicum infection. We evaluated the expression of Mzb1 in the liver and spleen of Schistosoma-infected mice using methods such as Western blot, qPCR, and immunohistochemistry. We also employed adeno-associated virus (AAV) to knock down Mzb1 gene expression, assessing the role of Mzb1 in the progression of schistosomiasis and its downstream pathways. Additionally, in vivo experiments were conducted using downstream endoplasmic reticulum stress agonists and inhibitors to evaluate the role of this pathway in the progression of schistosomiasis. Our findings demonstrated that Mzb1 was significantly upregulated in the liver and spleen tissues of infected mice. Knockdown of Mzb1 markedly reduced liver fibrosis and splenomegaly. Mzb1 was predominantly expressed in CD20-positive B cells and was found to activate endoplasmic reticulum (ER) stress. Inhibition of ER stress alleviated liver fibrosis and splenomegaly, while activation of ER stress exacerbated these pathological conditions and reversed the protective effects of Mzb1 knockdown. We identified Mzb1 as a key factor that promotes liver fibrosis and splenomegaly in schistosomiasis through the activation of ER stress. This novel pathogenic mechanism may provide a potential therapeutic target for the treatment of schistosomiasis-induced liver fibrosis.

Allergen immunotherapy (AIT) is the only etiological treatment for allergic rhinitis (AR) patients, yet the impact of allergen sensitization patterns on AIT efficacy remains unclear. This study aimed to assess the effectiveness of subcutaneous immunotherapy (SCIT) using a native house dust mite (HDM) allergen extract in Chinese AR patients with diverse HDM sensitization patterns. This prospective multicenter study across three allergy centers in China enrolled patients aged 5-65 diagnosed with HDM-induced AR. Serum-specific IgE testing for nine HDM components (Der p1, Der p2, Der p23, Der f1, Der f2, Der p5, Der p7, Der p10, Der p21) categorized patients into two groups: Group A with sensitization limited to major allergen components and Group B with sensitization to minor components with or without major components. Both groups underwent 1 year of HDM SCIT (Allergopharma, Germany), whose efficacy was assessed using the visual analogue scale (VAS) and combined symptom medication scores (CSMS). Serum IgE and IgG4 levels against the nine HDM components were measured pre- and post-treatment, and SCIT-related adverse reactions were recorded. The study enrolled 168 patients, with 75 in Group A and 93 in Group B. Group B patients had higher asthma prevalence and elevated baseline HDM sIgE and total IgE levels. After 1 year, Group B showed significantly greater CSMS reduction (67.70% vs. 59.09%, p = 0.03) and VAS improvement (66.67% vs. 50.00%, p = 0.01) compared to Group A. Group A had increased new sensitization risk to minor allergens (Der p5, Der p7, Der p21). No significant difference in SCIT efficacy was observed between patients with and without new sensitization. Both groups exhibited increased sIgG4 levels against all nine HDM allergens, with a more pronounced elevation of sIgG4 levels to Der p21 observed in Group B compared to Group A (p = 0.02). SCIT-related adverse reactions were comparable (p > 0.05). The native HDM allergen extract demonstrates efficacy in Chinese AR patients with varying sensitization patterns. It offers enhanced benefits for patients sensitized to minor allergens with or without major allergens of HDM, positioning it as the preferred option for individuals with AR. Chinese Clinical Trial Registry identifier: ChiCTR2300078642.

The effects of aspirin on hepatic steatosis and fibroinflammation are unclear. The study aimed to examine the association between aspirin use and liver magnetic resonance imaging (MRI)-derived liver fat and corrected T1 (cT1). We used UK Biobank imaging cohort data. Aspirin use was self-reported at baseline and imaging assessment, and the main exposures were aspirin use at imaging assessment and longitudinal aspirin use patterns (never users, initiators, discontinuers, vs. persistent users). Outcomes were MRI-derived liver fat (%) and cT1 (ms). Multivariable adjustment analyses and inverse probability of treatment weighting (IPTW) analyses were performed, accounting for demographic, lifestyle and clinical factors. We included 36 413 participants (mean age 64.6 years, 51.4% female). Aspirin use at imaging assessment was associated with lower liver fat (-0.35; 95% confidence interval [CI]: -0.51, -0.20) and slightly higher cT1 (5.13; 95% CI: 3.23, 7.03). Analyses on longitudinal aspirin use patterns showed that compared to never users, initiators and persistent users showed lower liver fat (-0.48; -0.69, -0.28) and (-0.24; -0.45, -0.02) and higher cT1 (2.94; 0.38, 5.49) and (8.31; 5.65, 10.97). IPTW analyses showed consistent results. In this large population-based cohort, aspirin use was linked to reduced liver fat, but a small, clinically insignificant (i.e., <80 ms) increase in cT1. These findings suggest aspirin may mitigate steatosis through metabolic pathways but does not necessarily rapidly reverse fibroinflammatory injury.

The clinical significance of Candida infection in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains poorly defined. This multicenter cohort study analyzed 11,925 hospitalized AECOPD patients from ten centers in China, grouped by Candida infection status. Subgroups were analyzed by Candida species and invasiveness. Primary outcome was 3-year all-cause mortality; secondary outcomes included in-hospital mortality, invasive mechanical ventilation (IMV), non-invasive ventilation (NIV), and intensive care unit (ICU) admission. Propensity score matching and Cox regression were used to adjust for confounders. Candida-positive AECOPD patients showed significantly worse short-term outcomes, including increased IMV (7.2% vs 3.8%) and NIV use (31.8% vs 18.2%), more ICU admissions (12.7% vs 8.9%), and prolonged hospitalization (15.97 vs 11.16 days, P < 0.001). No significant difference was observed in 30-day mortality between groups (aHR 1.13, 95% CI 0.63-2.03), but 3-year mortality was significantly higher (41.2% vs 30.5%, P < 0.001) in Candida positive group. Subgroup analyses showed no significant differences by species or invasiveness. Respiratory Candida infection is associated with worse short-term clinical outcomes and increased 3-year mortality in AECOPD patients, but is not an independent risk factor for in-hospital mortality. Neither species nor invasiveness classification offered prognostic value. Screening may identify high-risk patients, but evidence does not support species-specific or β-d-glucan (BDG)-guided therapy among this population.