Real-world effectiveness of belimumab in patients with lupus in China: RELIABLE observational cohort study protocol.

INTRODUCTION: The efficacy of belimumab in SLE has been demonstrated in randomised clinical trials, and its real-world effectiveness has been shown in studies in several countries. While belimumab was approved for treating SLE in China in 2019, data on its benefit in clinical practice are limited. This study will evaluate belimumab's effectiveness in China, using practical clinical measures, such as Lupus Low Disease Activity State (LLDAS), to add to the body of real-world evidence. METHODS AND ANALYSIS: The Real-world Effectiveness of beLImumAB in patients with systemic Lupus Erythematosus in China (RELIABLE) is an ambidirectional, observational descriptive cohort study across approximately 15 centres in China. Adults with SLE newly initiating belimumab with ≥1 measure of all five LLDAS components (SLE Disease Activity Index-2000; no new lupus disease activity; Physician Global Assessment; prednisolone-equivalent dose; immunosuppressants/biologics use) in the 3 months preceding belimumab initiation (index date) will be eligible and retrospectively and/or prospectively enrolled, depending on data availability. The retrospective follow-up will be ≤6 months, and retrospective and prospective patients will have a maximum 24-month follow-up. The primary objectives will be to describe the proportion of patients achieving LLDAS at 12 and 24 months post-index. The key secondary objective will be to describe the proportion of patients achieving LLDAS and each component at 3, 6, 9 and 18 months post-index. All data will be analysed descriptively; a statistical estimand will be applied to account for intercurrent events expected in a real-world setting. ETHICS AND DISSEMINATION: This study will comply with all applicable laws regarding patient privacy; institutional review board approval will be obtained before the study commencement. CONCLUSIONS: This study will evaluate belimumab's effectiveness in patients with SLE initiating belimumab in clinical practice in China. Using LLDAS will provide clinicians with valuable insights into the impact of belimumab on the treat-to-target strategy with a relevant measure that can be repeated across the clinical practice.

A lipid membrane-centric role of the SQSTM1/p62 body during autophagosome formation.

The phase separated SQSTM1/p62 body drives the formation of autophagosomes during macroautophagy/autophagy. However, the underlying mechanism by which the SQSTM1/p62 body acts during this process remains less understood. Recently, we reported that the SQSTM1/p62 body can work as a nucleation center to recruit local membrane sources for the expanding phagophore. Proteomics analysis reveals membrane vesicle-related components as important constituents of the SQSTM1/p62 body. ATG9- and ATG16L1-positive vesicles are recruited by the SQSTM1/p62 body as initial membrane sources of phagophores. ATG2 promotes the lipid transfer and vesicle fusion to further expand the membrane architecture of the initial phagophore. The lipid composition and content within the SQSTM1/p62 body is significantly affected by ATG2. The SQSTM1/p62 body also regulates the proper positioning and abundance of ATG9-positive vesicles. Furthermore, by spatially gathering ULK1 and membrane-anchored class III phosphatidylinositol (PtdIns) 3-kinase complexes, the SQSTM1/p62 body acts a local reaction platform to generate PtdIns-3-phosphate (PtdIns3P) to accelerate autophagosome maturation. These findings highlight a lipid membrane gathering model of the multifaceted SQSTM1/p62 body when driving autophagosome formation.

Extracellular vesicles in the treatment of oxidative stress injury: global research status and trends.

Objective: The aim of this study was to conduct a bibliometric analysis of the literature on "Extracellular Vesicles in the Treatment of Oxidative Stress Injury" and to reveal its current status, hot spots and trends. Methods: The relevant literature was obtained from the Web of Science Core Collection (WoSCC) on 29 April 2023. We performed clustering and partnership analysis of authors, institutions, countries, references and keywords in the literature through CiteSpace software and the bibliometric online analysis platform and mapped the relevant knowledge maps. Results: A total of 1,321 relevant publications were included in the bibliometric analysis, with the number of publications in this field increasing year by year. These included 944 "articles" and 377 "reviews". The maximum number of publications published in China is 512, and the maximum number of highly cited publications published in the United States is 20. Based on CiteSpace, the country collaboration network map shows close and stable collaboration among high-productivity countries. Based on WoSCC, there are 1706 relevant research institutions and 119 highly cited elite institutions, among which Kaohsing Chang Gung Men Hosp has the most extensive influence. Studies related to "Extracellular Vesicles in the Treatment of Oxidative Stress Injury" have been published in 548 journals. The keywords of the publications show the main research areas and breakthroughs. Based on WoSCC, the keywords of the research area "Extracellular Vesicles in the Treatment of Oxidative Stress Injury" were found to be as follows: exosome(s), extracellular vesicle(s), oxidative stress, inflammation, mesenchymal stem cells, apoptosis, microRNA (miRNA), mitochondria, biomarker, autophagy, angiogenesis and Alzheimer's disease. Analysis showed that "mesenchymal stem cells", "microRNA", "autophagy", "histology" and "therapeutic" emerged as highly explosive keywords. Conclusion: This study is the first to use visual software and data mining to assess the literature in the field of "Extracellular Vesicles in the Treatment of Oxidative Stress Injury". The research history, research status and direction in this field provide a theoretical basis for its scientific research.