Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE’s influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Objective: Childhood hearing impairment has potential repercussions on the mental well-being of both children and their parents. As a vulnerable population in accessing health care services, they may face specific challenges, especially during the COVID-19 pandemic. This cross-sectional study aims to investigate the association between childhood hearing impairment and the mental health of children and their parents, and to assess health care utilization of hearing-impaired children and its impact on mental outcomes for both during the COVID-19 pandemic.Methods: Using the National Health Interview Survey (NHIS) database, we analyzed data for 15,989 children aged 5–17 and their corresponding parents. The correlations between childhood hearing impairment and mental outcomes were examined using logistic regression models. The 2020 (quarter 3 and quarter 4)-2021 NHIS data was singled out and re-analyzed, focusing on the utilization of medical care during the COVID-19 pandemic.Results: After accounting for covariates, hearing-impaired children exhibited a higher frequency of anxiety (OR 2.33, 95% CI 1.79–3.02) or depression (OR 2.14, 95% CI 1.59–2.88). Parents of hearing-impaired children had significantly higher odds of a higher frequency of anxiety (OR 1.55, 95% CI 1.20–2.01) or depression (OR 1.73, 95% CI 1.30–2.29). Interaction effect of hearing impairment with survey year on parents’ mental health outcomes was observed (p for interaction <0.1). Children with hearing loss had higher odds of reporting delayed medical care (OR 2.00, 95% CI 1.11–3.59) or canceled medical care (OR 1.96, 95% CI 0.98–3.96, p = 0.059) due to the pandemic. Delayed medical care (OR 12.41, 95% CI 2.78–55.46) or canceled medical care (OR 6.26, 95% CI 1.28–30.75) due to the COVID-19 pandemic significantly contributed to the increase of anxiety frequency in hearing-impaired children.Conclusion: Childhood hearing impairment exhibits a substantial impact on children’s and parental mental health, which is further exacerbated by the COVID-19 pandemic. Families of hearing-impaired children appear to be in a vulnerable position during public health emergencies such as the COVID-19 pandemic, which can further exacerbate their mental outcomes.

Glioblastomas (GBMs) are highly aggressive and lethal primary brain tumors, known for their rapid proliferation, diffuse infiltration, and resistance to conventional therapies. Recent studies have highlighted the involvement of transient receptor potential melastatin 7 (TRPM7) in regulating GBM progression through its dual function as an ion channel and a serine/threonine protein kinase. TG100-115, initially characterized as a phosphoinositide 3-kinase γ/δ inhibitor, has recently been identified as a novel inhibitor of TRPM7 kinase. However, its potential pharmacological effects in GBM cells have not been fully elucidated. In this study, we investigated the anti-GBM effects of TG100-115 in U251 glioma cells. Cell viability and proliferation were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, whereas cell motility and invasiveness were determined through wound healing and transwell assays, respectively. Western blotting was used to detect the expression of key proteins involved in the apoptotic and molecular signaling pathways. Our findings revealed that TG100-115 significantly diminished the viability of U251 cells by promoting apoptosis while concurrently inhibiting the migratory and invasive activities of GBM cells. Mechanistically, TG100-115 enhanced apoptotic signaling by modulating B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, and cleaved caspase-3 levels. It also altered the phosphorylation status of protein kinase B and cofilin – both critical for cell survival and cytoskeletal dynamics. In conclusion, these findings suggest that TG100-115, by targeting TRPM7 kinase, exhibits promising therapeutic potential for GBM treatment and provides novel insights into targeting TRPM7-associated pathways in aggressive brain tumors.

Objective: Obstructive sleep apnea (OSA) is a common sleep-related respiratory disorder, yet many cases remain undiagnosed. Given the significant association between OSA and various adverse health outcomes, including cardiovascular complications, early identification and intervention are essential. The NoSAS score effectively screens individuals at high risk of OSA, thereby aiding in early detection.Material and methods: Data were collected from the Sleep Medicine Center at the First Affiliated Hospital of Guangzhou Medical University and the Sleep Research Institute at the Second Affiliated Hospital of Guangdong Medical University. Participants with a NoSAS score ≥8 were classified as high-risk, while those with scores <3 were classified as low-risk. Logistic regression was used to analyze the association between high-risk classification and cardiovascular disease morbidity.Result: A total of 2,164 participants with complete NoSAS score data were analyzed. In the high-risk group of 1,248 participants, cardiovascular disease incidence was 7.29%. In the adjusted model, the NoSAS high-risk group demonstrated a 2.2-fold increased risk of cardiovascular disease compared to the low-risk group (OR: 2.22, 95% CI: 1.17–4.18; p = 0.006). Age-stratified analysis indicated a significant association between NoSAS risk classification and cardiovascular disease in participants aged ≥60.Conclusion: In conclusion, the NoSAS high-risk group exhibited a higher burden of cardiovascular disease morbidity and served as an independent predictor of this condition.

Objectives: This study aims to investigate the association between the Systemic Immune-Inflammation Index (SII) and the development of pressure injuries (PI) in patients with chronic obstructive pulmonary disease (COPD). Additionally, a nomogram model based on the SII will be constructed to predict the probability of pressure injury (PI) occurrence in patients with COPD.Methods: A retrospective analysis was performed on the clinical data of 844 patients with COPD who were admitted to the Affiliated Hospital of Guangdong Medical University between June 2018 and December 2019. Logistic regression analysis was employed to identify risk factors associated with the development of PI, and the Wald chi-square test was used to select variables for constructing a predictive nomogram. The performance of the nomogram was assessed, followed by internal validation. Additionally, clinical data from 452 patients with COPD admitted to the Second Affiliated Hospital of Guangdong Medical University between January 2024 and December 2024 were prospectively collected for external validation.Results: A total of 844 patients with COPD were included in this study, with 590 cases in the training group and 254 cases in the internal validation group. The predictors included in the nomogram model were age, respiratory rate [Breathe (R)], duration of COPD history, Serum albumin (ALB), SII, paralysis, edema, and activities of daily living (ADL). The nomogram demonstrated strong predictive performance and calibration. The area under the curve and 95% confidence intervals were 0.77 (0.72–0.82) for the training group, 0.77 (0.70–0.85) for the internal validation group, and 0.73 (0.66–0.81) for the external validation group.Conclusion: This study identified the SII, age, respiratory rate, duration of COPD history, ALB, paralysis, and ADL as independent risk factors for the development of PI in patients with COPD. A nomogram model was successfully developed based on SII and validated through both internal and external testing. The findings suggest that SII is a reliable predictor of PI development in patients with COPD, and the model demonstrates strong predictive performance.