The endothelial-to-mesenchymal transition (EndMT) is an important source of fibrotic cells in idiopathic pulmonary fibrosis (IPF). However, how endothelial cells (ECs) are activated and how EndMT impact IPF remain largely elusive. Here, we use unsupervised pseudotemporal analysis to recognize the heterogeneity of ECs and reconstruct EndMT trajectory of bleomycin (BLM)-treated Tie2^creER/+;Rosa26^tdTomato/+ IPF mice. Genes like C3ar1 and Lgals3 (protein name galectin-3) are highly correlated with the transitional pseudotime, whose expression is gradually upregulated during the fate switch of ECs from quiescence to activation in fibrosis. Inhibition of galectin-3 via siRNA or protein antagonists in mice could alleviate the pathogenesis of IPF and the transition of ECs. With the stimulation of human pulmonary microvascular endothelial cells (HPMECs) by recombinant proteins and/or siRNAs for galectin-3 in vitro, β-catenin/GSK3β signaling and its upstream regulator AKT are perturbed, which indicates they mediate the EndMT progress. These results suggest that EndMT is essential to IPF process and provide potential therapeutic targets for vascular remodeling.

Background: Stroke is a globally prevalent disease that imposes a significant burden on health care systems and national economies. Accurate and rapid stroke diagnosis can substantially increase reperfusion rates, mitigate disability, and reduce mortality. However, there are considerable discrepancies in the diagnosis and treatment of acute stroke. Objective: The aim of this study is to develop and validate a stroke diagnosis and prediction tool using ChatGLM-6B, which uses free-text information from electronic health records in conjunction with noncontrast computed tomography (NCCT) reports to enhance stroke detection and treatment. Methods: A large language model (LLM) using ChatGLM-6B was proposed to facilitate stroke diagnosis by identifying optimal input combinations, using external tools, and applying instruction tuning and low-rank adaptation (LoRA) techniques. A dataset containing details of 1885 patients with and those without stroke from 2016 to 2024 was used for training and internal validation; another 335 patients from two hospitals were used as an external test set, including 230 patients from the training hospital but admitted at different periods, and 105 patients from another hospital. Results: The LLM, which is based on clinical notes and NCCT, demonstrates exceptionally high accuracy in stroke diagnosis, achieving 99% in the internal validation dataset and 95.5% and 79.1% in two external test cohorts. It effectively distinguishes between ischemia and hemorrhage, with an accuracy of 100% in the validation dataset and 99.1% and 97.1% in the other test cohorts. In addition, it identifies large vessel occlusions (LVO) with an accuracy of 80% in the validation dataset and 88.6% and 83.3% in the other test cohorts. Furthermore, it screens patients eligible for intravenous thrombolysis (IVT) with an accuracy of 89.4% in the validation dataset and 60% and 80% in the other test cohorts. Conclusions: We developed an LLM that leverages clinical text and NCCT to identify strokes and guide recanalization therapy. While our results necessitate validation through widespread deployment, they hold the potential to enhance stroke identification and reduce reperfusion time.

In-hospital delay reduces the benefit of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS), while factors affecting in-hospital delay are less well known in Chinese. We are aiming at determining the specific factors associated with in-hospital delay through a hospital based cohort. In-hospital delay was defined as door-to-needle time (DTN) ≥60min (standard delay criteria) or ≥75% percentile of all DTNs (severe delay criteria). Demographic data, time intervals [onset-to-door time (OTD), DTN, door-to-examination time (DTE), door-to-imaging time (DTI), door-to-laboratory time (DTL) and final-test-to-needle time (FTN, the time interval between the time obtaining the result of the last screening test and the needle time)], medical history and additional variables were calculated using Mann-Whitney U or Pearson Chi-Square tests for group comparison, and multivariate linear regression analysis was performed to identify independent variables of in-hospital delay. A total of 202 IVT cases were enrolled. The median age was 61 years and 25.2% were female. The cutoff points for the upper quartile of DTN (severe delay criteria) was 135min.When compared with the reference group without in-hospital delay, older age, shorter OTD and less referral were found in the standard delay group and male sex, presence with transient ischemic attacks or rapidly improving symptom, and with multi-model CT imaging were more frequent in the severe delay group. In the multivariate linear regression analysis, FTN (P<0.001) and DTL (P = 0.002) were significantly associated with standard delay; while DTE (P = 0.005), DTI (P = 0.033), DTL (P<0.001), and FTN (P<0.001) were positively associated with severe delay. There was not a significant change in the trend of DTNs during the study period (P = 0.054). In-hospital delay was due to multifactors in China, in which time delays of decision-making process and laboratory tests contributed the most. Efforts aiming at reducing the delay should be focused on the optimization for the items of screening tests and improvement of the pathway organization.

The generalization of successful efforts for reducing time delays in intravenous thrombolysis (IVT) could help facilitate its utility and benefits in acute ischemic stroke (AIS) patients. We searched the PubMed and Embase databases for articles reporting interventions to reduce time delays in IVT, published between January 1995 and September 2017. The IVT rate was chosen as the primary outcome, while the compliance rates of onset-to-door time (prehospital delay) and door-to-needle time (in-hospital delay) within the targeted time frame were the secondary outcomes. Interventions designed to reduce prehospital, in-hospital, or total time delays were quantitatively described in meta-analyses. The efficacy of postintervention improvement was illustrated as odds ratios (ORs) and 95% confidence intervals (95% CIs). In total, 86 papers (17 on prehospital, 56 on in-hospital, and 13 on total delay) encompassing 17,665 IVT cases were enrolled, including 28 American, 23 Asian, 30 European, and 5 Australian studies. The meta-analysis revealed statistically significant improvement in promoting IVT delivery after prehospital improvement interventions with an OR of 1.45 (95% CI, 1.23–1.71) for the new transportation protocol, 1.38 (95% CI, 1.11–1.73) for educational and training programs, and 1.83 (95% CI, 1.44–2.32) for comprehensive prehospital stroke code. The benefits of reducing in-hospital delay were much greater in developed western countries than in Asian countries, with ORs of 2.90 (95% CI, 2.51–3.34), 2.17 (95% CI, 1.95–2.41), and 1.89 (95% CI, 1.74–2.04) in American, European, and Asian countries, respectively. And telemedicine (OR, 2.26; 95% CI, 2.08–2.46) seemed to work better than pre-notification alone (OR, 1.94; 95% CI, 1.74–2.17) and in-hospital organizational improvement programs (OR, 2.10; 95% CI, 1.97–2.23). Mobile stroke treatment unit and use of a comprehensive stroke pathway in the pre- and in-hospital settings significantly increased IVT rates by reducing total time delay, with ORs of 2.01 (95% CI, 1.60–2.51) and 1.77 (95% CI, 1.55–2.03), respectively. Optimization of the work flow with organizational improvement or novel technology could dramatically reduce pre- and in-hospital time delays of IVT in AIS. This study provided detailed information on the net and quantitative benefits of various programs for reducing time delays to facilitate the generalization of appropriate AIS management.

Background: Translational failures in anti-adhesion molecule therapies after stroke reveal the necessity of developing new strategies that not only interrupt leukocyte recruitment but also consider the inhibition of endothelial cell inflammation, verification of therapeutic time window, and normal function maintenance of circulating leukocytes. Our study focused on the potential therapeutic value of CD151 downregulation in improving current anti-adhesion molecule therapies. Methods: Lentivirus intracerebroventricular administration was conducted to inhibit the CD151 expression and observe its functional influence on neurological injuries and outcomes. Then, immunohistochemistry and myeloperoxidase activity assessment were performed to explore the effects of CD151 expression on neutrophil and monocyte recruitment after rat cerebral ischemia. Primary rat brain microvascular endothelial cells were subjected to oxygen glucose deprivation and reoxygenation to elucidate the underlying working mechanisms between CD151 and VCAM-1. Results: The CD151 downregulation remarkably reduced neurological injuries and improved neurological outcomes, which were accompanied with reduced neutrophil and monocyte infiltration after the CD151 downregulation. The VCAM-1 expression was remarkably decreased among the adhesion molecules on the endothelial cell responsible for neutrophil and monocyte infiltration. The activation of p38 MAPK and NF-κB pathways was restricted after the CD151 downregulation. p38 MAPK and NF-κB inhibitors decreased the VCAM-1 expression, and p38 acted as an upstream regulator of NF-κB. However, CD151 downregulation did not directly influence the neutrophil and monocyte activation. Conclusions: Overall, CD151 regulated the expression of adhesion molecules. It also played a critical role in suppressing VCAM-1-mediated neutrophil and monocyte infiltration via the p38/NF-κB pathway. This study possibly provided a new basis for improving current anti-adhesion molecule therapies.