Sepsis-associated acute kidney injury (S-AKI) is a critical condition characterized by renal tubular epithelial cell apoptosis and abnormal cytoskeleton. This study aims to investigate the role of the m6A modification-dependent protein HNRNPC in regulating renal cell apoptosis and cytoskeleton in S-AKI. Dot blot analysis was employed to assess the total m6A levels. Cell viability, flow cytometry, and fluorescent phalloidin staining were used to evaluate the role of HNRNPC in CD80-dependent apoptosis and cytoskeletal remodeling. RNA sequencing and subsequent data analysis highlighted the involvement of the NF-κB signaling pathway. Luciferase reporter assays and Western blot were used to establish that HNRNPC transcriptionally promotes CD80 expression. Bioinformatics, EMSA, and ChIP assays further confirmed the role of NF-κB in regulating CD80. Additionally, MeRIP-qPCR and RNA m6A quantification demonstrated that HNRNPC facilitates apoptosis through m6A-dependent regulation of NF-κB. Induction of HNRNPC to a higher level can induce apoptosis and cytoskeletal deformation in renal tubular cells. Meanwhile, CD80 was essential for HNRNPC-induced tubular injury. Further experiments showed that HNRNPC regulated NF-κB mRNA dependent on m6A modification. Moreover, NF-κB acted as a transcription factor to promote CD80 expression. In vivo experiments further verified the relationships between HNRNPC, NF-κB, and CD80 and demonstrated the significance of HNRNPC in CD80-associated apoptosis. This study elucidates the molecular mechanisms underlying the pathogenesis of S-AKI and highlights the potential of HNRNPC and CD80 as therapeutic targets to reduce renal damage in S-AKI. Graphical Abstract

Objective: Idiopathic refractory membranous nephropathy (IRMN) is a subset of nephrotic syndrome with a high risk of progression to end-stage renal disease, yet treatment options remain limited. Obinutuzumab, a humanized type II anti-CD20 antibody, induces efficient CD20+ cell depletion, leading to favorable immunological and proteinuria responses in IRMN. This study sought to assess the effectiveness and safety of obinutuzumab for treating IRMN. Methods: A total of 31 patients with IRMN were enrolled and received obinutuzumab therapy. They were followed for 12 months. The primary endpoint was the remission rate (complete or partial remission). Secondary outcomes included changes in proteinuria, serum albumin, serum creatinine, anti-PLA2R antibody levels, CD20/CD19 cell counts, and adverse events. Results: At 12 months, the overall remission rate was 80%, with 16% achieving complete remission and 64% achieving partial remission. The median time to remission was 4.5 months (IQR 2.0–7.0 months). The immunological remission rates at 3, 6, 9, and 12 months were 70, 83, 90, and 93%, respectively. Regarding anti-PLA2R antibodies, 80% of patients showed a rapid decline within the first 3 months ( p < 0.001), with 64% achieving a > 50% reduction from baseline by month 3. At the last follow-up, all patients had achieved seroconversion to anti-PLA2R antibody negativity. Adverse events included infusion-related reactions such as fever, hypotension, tachycardia, and flushing. No deaths occurred. Conclusion: Obinutuzumab effectively induces remission in patients with IRMN and demonstrates a tolerable safety profile.

Background: Vitamin A deficiency (VAD) remains a critical public health burden in China, particularly affecting children and reproductive-age women. A comprehensive analysis of its long-term trends is essential for guiding nutritional interventions.Methods: Utilizing data from the Global Burden of Disease (GBD) 2021 study covering 1990 to 2021, we examined age-standardized incidence, prevalence, disability-adjusted life years (DALYs), and sociodemographic factors influencing VAD in China. Joinpoint regression detected temporal inflection points, and Bayesian age-period-cohort (BAPC) modeling forecasted incidence up to 2040. Frontier analysis correlated burden with the socio-demographic Index (SDI) across 204 countries.Results: In 2021, China reported 23.19 million new VAD cases, with higher age-standardized incidence in females (2,094.3/100,000) versus males (1,821.07/100,000). A bimodal age distribution peaked in children (<14 years, male-predominant DALYs) and young adults (20–34 years, female-predominant incidence). From 1990–2021, age-standardized rates declined by 81.2% (incidence) and 81.2% (prevalence), surpassing global reductions. Critically, a 2013 inflection point reversed sex disparities: male burden exceeded females before 2013, but female rates dominated thereafter. Sub-Saharan Africa experienced the highest burden globally, with a negative correlation between SDI and VAD incidence (R² = 0.72, p < 0.001). BAPC projections indicate persistent declines through 2040, but males will retain higher incidence than females.Conclusion: Despite substantial progress, VAD persists with evolving sex-age disparities. The 2013 sex burden reversal and dual vulnerability of children/young adults necessitate sex-stratified interventions. Integration of supplementation programs with socioeconomic development is vital for eliminating VAD in China and high-burden regions.