Wenjia Ai

Abdominal aortic aneurysm (AAA) enlargement is a major risk factor for aneurysm rupture and the development of abdominal aneurysm dissection (AAD). However, reliable serum biomarkers for predicting AAD occurrence remain lacking. This study was designed to identify circulating serum markers capable of predicting AAA progression and AAD formation. Patients diagnosed with AAA or AAD at our institution between 2020 and 2025 were enrolled and corresponding clinical characteristics were analyzed. Peripheral blood levels of arachidonic acid (AA) and 12–HETE were measured using ELISA, and Alox12 mRNA expression was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Candidate serum biomarkers associated with AAA enlargement and AAD development were investigated using a multi-modal approach integrating computed tomography (CT) images, serum metabolic profiles, and aneurysm wall tissue analyses. A total of 52 AAA patients and 42 AAA patients were included in the analysis. Elevated serum 12–HETE and TG levels were significantly associated with AAA enlargement and the occurrence of AAD, whereas AA levels showed no significant difference between groups. Dysregulated AA/12–HETE metabolism is an independent risk factor for aneurysmal enlargement in AAA and AAD, while 12–HETE and TG help to discriminate AAD from AAA.

Background: Identifying high‐risk patients with acute pulmonary embolism is vital for improving disease prognosis. However, current guidelines and research on risk factors are insufficient to meet clinical needs. This study was aimed at exploring novel risk factors to predict in‐hospital mortality. Methods: We utilized a patient cohort from the Medical Information Mart for Intensive Care Version IV (MIMIC‐IV) database as training cohort. Major analyses included screening risk factors for in‐hospital mortality, correlation analysis via smooth curve fitting, multivariate Cox regression, and subgroup analysis. The findings were further validated with our own institute patient cohort. Results: Among 1463 adult patients with acute pulmonary embolism in the MIMIC‐IV database, the overall in‐hospital mortality rate was 17.8%. A nonlinear correlation was observed between urine output and in‐hospital mortality. A urine discharge less than 0.85 mL/kg/h was used as the threshold and was negatively associated with the risk for in‐hospital death. Compared to patients with urine value < 0.5 mL/kg/h, the risk for in‐hospital mortality reduced by 36% and 48% in patients with urine values of 0.5–0.85 mL/kg/h and > 0.85 mL/kg/h, with the hazard ratios of 0.64 (0.47, 0.87) and 0.52 (0.38, 0.72), respectively. This association remained significant in the subgroup analysis after adjusting for age, gender, hypotension, and low oxygen saturation. Our validation patient cohort ( n = 151) further confirmed the strong association of the urine value with in‐hospital mortality and consistent cutoff value. Conclusion: Our study revealed a negative association of urine output with in‐hospital mortality in acute pulmonary embolism patients, with the optimal urine output being significantly higher than the value of other critical illnesses.

Type 1 diabetes (T1D) is an autoimmune disease that is caused by autoreactive T cell-mediated destruction of insulin-producing β cells in the pancreatic islets. Although naive autoreactive T cells are initially primed by islet antigens in pancreas-draining lymph nodes (pan-LNs), the adhesion molecules that recruit T cells into pan-LNs are unknown. We show that high endothelial venules in pan-LNs of young nonobese diabetic mice have a unique adhesion molecule profile that includes strong expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Anti-MAdCAM-1 antibody blocked more than 80% of the migration of naive autoreactive CD4⁺ T cells from blood vessels into pan-LNs. Transient blockade of MAdCAM-1 in young nonobese diabetic mice led to increased numbers of autoreactive regulatory CD4⁺ T cells in pan-LNs and pancreas and to long-lasting protection from T1D. These results indicate the importance of MAdCAM-1 in the development of T1D and suggest MAdCAM-1 as a potential therapeutic target for treating T1D.

Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of treatment with the gasdermin D inhibitor necrosulfonamide on experimental AAAs. AAAs were induced in male apolipoprotein E-deficient mice by subcutaneous angiotensin II infusion (1000 ng/kg body weight/min), with daily administration of necrosulfonamide (5 mg/kg body weight) or vehicle starting 3 days prior to angiotensin II infusion for 30 days. Necrosulfonamide treatment remarkably suppressed AAA enlargement, as indicated by reduced suprarenal maximal external diameter and surface area, and lowered the incidence and reduced the severity of experimental AAAs. Histologically, necrosulfonamide treatment attenuated medial elastin breaks, smooth muscle cell depletion, and aortic wall collagen deposition. Macrophages, CD4⁺ T cells, CD8⁺ T cells, and neovessels were reduced in the aneurysmal aortas of necrosulfonamide- as compared to vehicle-treated angiotensin II-infused mice. Atherosclerosis and intimal macrophages were also substantially reduced in suprarenal aortas from angiotensin II-infused mice following necrosulfonamide treatment. Additionally, the levels of serum interleukin-1β and interleukin-18 were significantly lower in necrosulfonamide- than in vehicle-treated mice without affecting body weight gain, lipid levels, or blood pressure. Our findings indicate that necrosulfonamide reduced experimental AAAs by preserving aortic structural integrity as well as reducing mural leukocyte accumulation, neovessel formation, and systemic levels of interleukin-1β and interleukin-18. Thus, pharmacologically inhibiting gasdermin D activity may lead to the establishment of nonsurgical therapies for clinical AAA disease.