zolpidem tartrate (Stilnox CR / FK199B / Stilnoxium)

Impact of RAS inhibitors on 2-year mortality and disease progression in chronic mitral regurgitation.

Li Chenyang C, Ye Yunqing Y, Wang Can C, Hu Xiangming X et al.

Chronic mitral regurgitation (MR) is associated with adverse clinical outcomes, and the role of renin-angiotensin system inhibitors (RASI) in patients with MR remains uncertain. This study evaluated the association between RASI use patterns and 2-year all-cause mortality and disease progression in patients with primary MR (PMR) and secondary MR (SMR). This registry-based study included 3,297 patients with moderate-to-severe chronic MR from the China Valvular Heart Disease registry, including 955 with PMR and 2,342 with SMR. RASI use was assessed at baseline and during follow-up, and patients were categorized as always users, never users, or inconsistent users. The primary endpoint was 2-year all-cause mortality. The secondary endpoint was change in MR severity. Associations between RASI use and outcomes were assessed using multivariable Cox regression, propensity-score matching, and time-varying Cox analyses. Consistent RASI use was associated with lower 2-year all-cause mortality in both PMR and SMR. In multivariable Cox regression, never users had higher mortality risk than always users in both cohorts (PMR: HR 5.40, 95% CI 1.58-18.47, P = 0.007; SMR: HR 5.09, 95% CI 2.85-9.09, P < 0.001). Inconsistent users also had higher mortality risk than always users (PMR: HR 7.56, 95% CI 2.25-25.37, P = 0.001; SMR: HR 3.29, 95% CI 1.85-5.84, P < 0.001). Propensity-score-matched analyses showed broadly consistent results. Time-varying Cox analyses demonstrated directionally consistent associations in the overall cohort and SMR during selected follow-up intervals, whereas in PMR the interval-specific estimates were less stable and did not reach statistical significance. Consistent RASI use was also associated with improvement in MR severity, particularly in SMR and in patients without guideline-based indications for valvular intervention. In patients with moderate-to-severe chronic MR, consistent RASI use was associated with lower 2-year all-cause mortality and improvement in MR severity. These findings suggest that RASI therapy may have a role in optimized medical management for selected patients with chronic MR, particularly those with SMR or impaired/borderline LV function. Further prospective studies are needed to confirm whether RASI directly improves survival or delays MR progression. This study utilized data from the China Valvular Heart Disease (China-VHD) registry (NCT03484806).

Corrigendum to "Hyaluronic acid-modified hydrothermally synthesized iron oxide nanoparticles for targeted tumor MR imaging" [Biomaterials 35 (2014) 3666-3677].

Li Jingchao J, He Yao Y, Sun Wenjie W, Luo Yu Y et al.

Identification of Genetic Diagnostic Markers for Systemic Lupus Erythematosus.

Liu Qianqian Q, Yang Hairong H, Dang Chunxiao C, Song Xingxing X

Systemic lupus erythematosus (SLE) is a complex and heterogeneous systemic autoimmune disease associated with poor treatment outcomes. While previous studies have indicated a genetic predisposition to SLE, the underlying mechanisms remain poorly understood. This study aimed to identify diagnostic targets with potential genetic associations to SLE by leveraging bioinformatics and the Mendelian randomization (MR) approach. Six datasets (GSE30153, GSE39088, GSE50635, GSE50772, GSE61635, and GSE110169) were obtained from the GEO database for differential expression analysis to identify differentially expressed genes (DEGs). Weighted gene coexpression network analysis (WGCNA) was then performed, and the most relevant module was intersected with the DEGs to identify candidate genes with potential diagnostic value. Subsequently, machine learning algorithms were applied to screen diagnostic genes, and their performance was evaluated using receiver operating characteristic (ROC) curves and confusion matrices. MR analysis was conducted to identify diagnostic genes with genetic associations. A protein-protein interaction (PPI) network was constructed to identify core genes. Finally, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analysis were performed. Differential expression analysis identified 244 DEGs, and WGCNA revealed a highly relevant module. Intersecting this module with the DEGs produced 136 candidate genes. Machine learning algorithms and MR analysis further refined the selection, identifying five diagnostic genes: GBP1, IFI6, KLHDC8B, OAS3, and ZCCHC2, all of which were shown to be well-aligned with their respective drugs. The PPI network highlighted GBP1, IFI6, and OAS3 as core genes, which showed significant correlations with immune cell infiltration. Our study identified GBP1, IFI6, and OAS3 as core genes implicated in SLE pathogenesis, providing novel insights into its molecular mechanisms and potential therapeutic targets.

Moringa oleifera seed rennet as a novel hydrocolloid coagulant in the production of mozzarella cheese: Effects on function, texture, structure, and rheology.

Zhang Lu L, Yang Yan Y, Li Ling L, Deng Youtao Y et al.

This study evaluated the potential of Moringa oleifera seed rennet (MSR) as a novel hydrocolloid coagulant for mozzarella cheese production compared with commercial rennets. Mozzarella cheeses were manufactured using MSR and 3 commercial rennets (calf rennet, CR, papain rennet, PR, rice black mold rennet, MR). MSR-treated cheese (MSRC) showed comparable nutritional value to calf rennet cheese (CRC), with no significant differences in protein and fat content (P > 0.05), while exhibiting superior hardness and elasticity compared with PR- and MR-treated cheeses.Mechanistically, MSR specifically hydrolyzed κ-casein, increasing α-helix content and fluorescence intensity while reducing free sulfhydryl content, indicating strengthened protein secondary and tertiary structures. These changes led to a denser, more stable protein gel network with smaller pore sizes and more uniform casein distribution, as confirmed by microstructure analysis. Rheologically, MSRC exhibited higher G' and G" values, indicating enhanced elastic and viscous gel-like behavior. Correlation analysis revealed strong positive correlations between fat content and hardness (r = 0.995) and between protein content and elasticity (r = 0.951), while α-helix structure was negatively correlated with moisture (r = -0.980), resilience (r = -0.915), and meltability (r = -0.880). These findings demonstrate that MSR is a viable plant-based, sustainable alternative to commercial rennets for mozzarella cheese production.