Background Oxidized low-density lipoprotein (ox-LDL) provokes endothelial dysfunction central to atherogenesis. The mechanosensitive channel Piezo1 regulates Ca2+ influx and may intersect with extracellular cues such as cartilage oligomeric matrix protein (COMP). We investigated whether COMP-associated Piezo1 signaling is involved in endothelial injury and EndMT-like changes in vitro and in vivo.Methods Human umbilical vein endothelial cells were exposed to ox-LDL with Piezo1 inhibition (GsMTx-4) or activation (Yoda1), recombinant COMP dosing, or COMP overexpression. Apoptosis, nuclear morphology, and viability were assessed by Annexin V-FITC/PI flow cytometry, Hoechst staining, and MTT; nitric oxide (NO) by Griess; intracellular Ca2+ by Fura-2 AM; and Ca2+-Mg2+-ATPase and Na+-K+-ATPase activities by micro-colorimetry. Co-immunoprecipitation was performed to assess the association between COMP and Piezo1. ATP2B1 and ATP1A1 protein expression, intracellular ATP levels, CD31 and alpha-SMA expression, and EndMT-related transcription factors were additionally evaluated by immunoblotting, ATP assay, immunofluorescence, and RT-qPCR. Expression of COMP, Piezo1, eNOS, and related targets was quantified by RT-qPCR and immunoblotting. In ApoE-/- mice with diet-induced atherosclerosis, Piezo1 was pharmacologically modulated; cardiac performance (echocardiography), hemorheology, aortic histology, alpha-SMA immunofluorescence, NO and ATPase activities, and aortic transcripts/proteins (including KATP subunits) were evaluated.Results Ox-LDL triggered endothelial apoptosis, loss of viability, NO suppression, and elevated intracellular Ca2+ with inverse changes in membrane ATPase activities; GsMTx-4 treatment mitigated these effects, whereas Yoda1 treatment intensified them. Co-immunoprecipitation supported a biochemical association between COMP and Piezo1. Ox-LDL also reduced ATP2B1 and ATP1A1 expression and intracellular ATP levels, decreased CD31, and increased alpha-SMA and the EndMT-related transcription factors Snail, Slug, Twist, and ZEB1; these changes were partially reversed by GsMTx-4 and further aggravated by Yoda1. Recombinant COMP and COMP overexpression aggravated ox-LDL injury and aligned with higher COMP/Piezo1 and lower eNOS at mRNA and protein levels. In atherosclerotic mice, GsMTx-4 treatment was associated with improved cardiac indices and hemorheology, increased NO and ATPase-related readouts, reduced aortic alpha-SMA-associated changes and histologic remodeling, and shifted vascular expression toward lower COMP/Piezo1 and higher eNOS; Yoda1 treatment produced the opposite pattern, while KATP-related changes were directionally associated with pharmacologic Piezo1 modulation.Conclusion COMP-associated Piezo1 signaling is linked to Ca2+ loading, ATPase-related dysfunction, and impaired eNOS/NO signaling in association with endothelial injury and EndMT-like changes. Piezo1 modulation confers partial vascular protection in these experimental settings and supports further investigation of this pathway in atherosclerosis.
Maternal erythrocyte indices, including the mean corpuscular hemoglobin concentration (MCHC) and red blood cell distribution width (RDW), are potential indicators of adverse birth outcomes. However, their association with neonatal 17-hydroxyprogesterone (17OHP) levels remains unexplored. This study investigated the relationship between maternal erythrocyte indices in late pregnancy and neonatal 17OHP levels, and secondarily with fetal growth outcomes. This retrospective cohort study included 10,141 mother–neonate pairs. Maternal MCHC and RDW were categorized into low, normal, and high groups based on the clinical reference ranges. Linear regression was used for neonatal 17OHP levels and birth weight, and logistic regression was used for small-for-gestational age (SGA) and large-for-gestational age (LGA). Generalized additive models and two-piecewise linear regression were used to explore the nonlinear relationships and threshold effects. The models were adjusted for maternal age, pre-delivery body mass index, parity, gestational age, blood pressure, pregnancy complications, assisted reproductive technology, delivery mode, and neonatal sex. 17OHP models were additionally adjusted for Apgar score and postnatal age at sampling. Elevated maternal MCHC (> 348 g/L) was independently associated with higher neonatal 17OHP levels (adjusted β = 2.30 nmol/L; P < 0.001). Compared with the low RDW (< 12.3
To assess the safety and efficacy of supraglottic airway (SGA) versus endotracheal intubation (ETI) for improving resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA) via a systematic review and meta-analysis. Eight databases, including PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM, were searched for eligible controlled trials (including both randomized controlled trials and clinical controlled trials) from inception to May 31, 2025. Risk of bias was assessed using the Cochrane RoB 2 tool for randomized controlled trials and the ROBINS-I tool for non-randomized clinical controlled trials. Meta-analysis, sensitivity analysis, and trial sequential analysis (TSA) were performed via RevMan 5.3 and TSA software. The evidence quality was graded via the GRADE framework. The primary outcomes included the airway establishment time and Return of Spontaneous Circulation (ROSC), and the secondary outcomes included the first-attempt advanced airway success, mortality, favorable neurological prognosis, time to return of spontaneous circulation (ROSC), time to SpO2 improvement, peripheral oxygen saturation (SpO2), and adverse events. Thirty-one controlled trials (22,396 patients), comprising 21 randomized controlled trials and 10 clinical controlled trials, were included. Compared with ETI, SGA was associated with a significantly shorter airway establishment time (mean difference (MD) =− 77.93 s; 95
Acute decompensated heart failure (ADHF) with reduced ejection fraction (HFrEF) carries substantial short-term risk. We evaluated routinely available clinical, hematologic, and electrocardiographic factors associated with in-hospital mortality and severe pre-admission functional limitation. This retrospective cohort included 100 adults hospitalized with ADHF and HFrEF. In-hospital death was the primary outcome. Because 16 deaths occurred, mortality associations were estimated using a three-variable Firth penalized logistic model including elevated jugular venous pressure (JVP), white blood cell (WBC) count, and Bazett-corrected QTc. Model discrimination, calibration, Brier score, and 1,000-resample bootstrap internal validation were assessed. Severe pre-admission functional limitation was analyzed as NYHA class IV versus classes II–III using a separate three-variable binary logistic model. Broad univariable analyses were exploratory and were adjusted using the Benjamini–Hochberg false-discovery-rate procedure. Sixteen patients (16
The triglyceride–high-density lipoprotein–glucose–body (TyHGB) index is an emerging indicator of metabolic dysfunction. We aimed to examine its relationship with reduced kidney function among older Chinese individuals (≥ 65 years). This cross-sectional study included 9231 older adults who underwent annual health examinations at the Kunshan Jinxi People’s Hospital. Reduced kidney function was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 using the 2021 CKD-EPI equation (low eGFR). Multivariable logistic regression, restricted cubic splines, subgroup analyses, and receiver operating characteristic (ROC) curves were employed. The TyHGB index was significantly higher in participants with reduced kidney function. In fully adjusted models, individuals in the highest TyHGB quartile had higher odds of low eGFR than those in the lowest quartile (OR = 1.866, 95
