PLA Navy General Hospital

Endothelial dysfunction (ED) is a key pathophysiological mechanism in cardiovascular diseases (CVD). The Endothelial Activation and Stress Index (EASIX), derived from routine laboratory markers, has been proposed as a surrogate indicator of endothelial stress. However, its relevance to CVD burden and long-term outcomes in the general population remains uncertain. We analyzed data from 38,713 adults aged ≥20years enrolled in the U.S. National Health and Nutrition Examination Survey (NHANES, 1999-2018), representing approximately 1.7 billion individuals after weighting. EASIX was calculated as [LDH (U/L)×creatinine (mg/dL)] / platelet count (109/L) and log₂-transformed. Weighted logistic regression assessed the association between EASIX and CVD prevalence, while weighted Cox models examined its relationship with all-cause (ACM) and cardiovascular mortality (CVM). Restricted cubic spline analyses evaluated potential nonlinear trends, and subgroup analyses tested effect modification. Among 38,713 participants, 4131 had CVD. Higher EASIX values were independently associated with greater CVD prevalence (adjusted OR=1.43, 95% CI: 1.34-1.53). Each log₂ increase in EASIX corresponded to higher risks of ACM (HR=1.39, 95% CI: 1.28-1.51) and CVM (HR=1.54, 95% CI: 1.38-1.72). Individuals in the top EASIX quartile exhibited more than double the mortality risks compared with those in the lowest quartile. Associations were nonlinear and consistent across most subgroups. EASIX demonstrated independent, nonlinear associations with both CVD prevalence and long-term mortality. These findings highlight EASIX as a practical, cost-efficient biomarker for cardiovascular risk stratification in population settings.

The healing of infected tendons is hindered by mechanical dysfunction, tissue adhesion, bacterial colonization, and immune imbalance. Inspired by the biphasic "adhesion-lubrication" structure of tendon sheaths, we developed a Janus hydrogel, named HAPP@H-EXO, for spatiotemporal repair. The material exhibits antifatigue properties and redistributes mechanical stress through a dynamic network formed by norbornylated PVA and boronic acid-modified hyaluronic acid-PVA. Its high-adhesion side integrates tissue via borate and hydrogen bonds, whereas the lotus leaf-induced low-adhesion side prevents postsurgical adhesion. The incorporation of oligo-polyethyleneimine and phenylboronic acid groups traps and kills bacteria, overcoming resistance. The pH-responsive release of hypoxic tendon stem cell exosomes reprogrammes macrophages via inhibition of the NF-κB pathway, reducing inflammation and promoting regeneration. In an infected Achilles tendon model, HAPP@H-EXO eliminated MRSA, suppressed early inflammation, and enhanced regeneration. Within 8 weeks, it significantly improved biomechanical strength, prevented adhesion, and restored motor function, establishing a mechanoimmunotherapeutic strategy for infected tissue regeneration.

This paper addresses the challenges of constructing a knowledge graph for civil aviation incidents, focusing on long entity lengths, the presence of hybrid and composite entities, and the similarities in form features of domain-specific entity names. We propose a method for building the civil aviation incident knowledge graph based on a multi-attribute attention alignment method using LLM twin networks. Structural similar entities from the civil aviation knowledge base are input into a "character embedding + fine-tuning layer" pre-trained language model (Embedding Pre-trained Language Models, EPLMs) for pre-training. By leveraging the characteristics of the twin network, a set of entities shares network weights during encoding, allowing the two sub-networks to acquire comprehensive semantic representations of entities and to determine the relative importance of each attribute.thereby improving the completeness of the civil aviation knowledge graph and enhancing the quality and standardization of the knowledge graph. Results from experiments show that the proposed model's F1 score is 96.72%. validating the model's effectiveness compared to other models.

BackgroundMitochondrial dyshomeostasis plays an important role in neuronal damage after cerebral ischemia-reperfusion, and Miro1 is a core protein that regulates mitochondrial homeostasis. In this study, we aimed to investigate the neuroprotective effects of bone marrow-derived mesenchymal stem cells (BMSCs) via mitochondrial homeostasis in rats after cardiac arrest (CA), and to clarify the role that the protein Miro1 plays in this protective efficacy.MethodsThe study compared the effects of BMSCs in which Miro1 was overexpressed BMSCs (BMSCs-mirohi), knocked down (BMSCs-mirolo), and unmodified BMSCs on mitochondrial homeostasis in hippocampal neurons to evaluate their neuroprotective effects of these cells in a rat model of global cerebral ischemia-reperfusion injury. Rats underwent CA modeling for 5 min and received cardiopulmonary resuscitation (CPR). Two hours after the restoration of spontaneous circulation, 1 mL of PBS or 1 mL containing 1 × 106 BMSCs (normal, mirohi, or mirolo) were injected via the femoral vein. The neurological function of rats was assessed based on Neurological Disability Score (NDS) values. Brain histopathological examination was conducted to evaluate brain injury by measuring oxidative stress levels and the apoptosis rate of hippocampal neurons. Immunoblotting and transmission electron microscopy were applied to detect the expression of mitophagy-related proteins in hippocampal neurons. Immunofluorescence was used to track the mitochondria in BMSCs and observe mitochondrial transfer. Additionally, the membrane potential level, oxidative stress level, and ATP content of mitochondria in hippocampal neurons were measured to assess the impact of transplanted BMSCs on mitochondrial quality in these hippocampal neurons.ResultsImmunofluorescence staining revealed the presence of mitochondria from MitoTracker-labeled BMSCs in rat hippocampal neurons post-CPR. Additionally, the fluorescence intensity of TOMM20 was notably increased following the transplantation of BMSCs. Through immunoblotting experiments, we identified that BMSCs amplified the post-CPR protein expression of LC3, p62, PINK1 and parkin in hippocampal neurons. The number of autophagosomes significantly increased in hippocampal neurons following BMSC transplantation, as observed through transmission electron microscopy. Flow cytometry, Hematoxylin and Eosin (HE) staining, and NDS scoring indicated that BMSCs effectively reduced reactive oxygen species accumulation in hippocampal neurons and mitochondria after CPR. Furthermore, they restored mitochondrial membrane potential and ATP levels in the hippocampus while decreasing apoptosis, ultimately contributing to the restoration of neurological function. Additionally, unlike BMSCs-mirolo, BMSCs-mirohi were able to significantly enhance the efficiency of BMSC-mediated mitochondrial transfer and enhance mitophagy. This amplification, in turn, was found to bolster the protective impact of BMSCs on hippocampal neurons during CPR, thereby contributing to the restoration of rat neurological function.ConclusionsThese analyses revealed that BMSC transplantation has a dual protective effect by facilitating healthy mitochondrial transfer and promoting the autophagic degradation of damaged mitochondria, effectively enhancing hippocampal neuronal mitochondrial function following CA while reducing neuronal apoptosis, restoring neuronal function, and alleviating neuropathological damage. Moreover, Miro1 can enhance the efficiency of mitochondrial transfer and promote BMSC-mediated mitophagy induction, thereby optimizing the therapeutic effect of BMSCs.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04724-5.

To investigate the images and treatment differences for Type IIIa atlantoaxial rotary dislocation (AARD) by comparing the imaging characteristics of patients with Type III and Type IIIa AARD. The present study retrospectively analyzed a cohort of 35 patients who underwent posterior C1-C2 intra-articular fusion due to AARD from our hospital database. Among them, 23 patients were diagnosed with Type III AARD, while the remaining 12 patients were diagnosed with Type IIIa AARD. The imaging characteristics and clinical data were reviewed and compared. Type III AARD demonstrated significantly greater traction reducibility than Type IIIa (18/23 vs. 4/12 cases, P < 0.05), with longer operative times required for Type IIIa (P < 0.05). All patients achieved successful fusion without complications, showing significant Visual Analog Scale Score for Neck Pain (VASSNP) improvement (P < 0.05) but unchanged Japanese Orthopedic Association (JOA) scores. Radiographically, Type IIIa exhibited higher C2 facet deformity rates (10/12 vs. 9/23), more severe Ishii Grade III involvement, and larger C1-C2 separation angle (SEA)/lateral inclination angle (LIA) measurements (P < 0.05), while atlanto-dens interval (ADI), C2-C7 angle, and T1-slope (T1S) showed no intergroup differences. The SEA has a significant positive correlation with the LIA (r = 0.711, P < 0.001). In conclusion, compared to Type III AARD, Type IIIa AARD exhibits a larger SEA and LIA, rendering it more susceptible to C2 facet joint deformities and consequently posing greater challenges during surgical reduction of the atlantoaxial joint.

This study was to investigate the association between oral anticoagulant use and 28-day mortality and in-hospital mortality in patients with acute respiratory distress syndrome (ARDS). A total of 1754 ARDS patients were identified in database from 2008 to 2022 in this cohort study. Univariable and multivariable cox regression models were applied to assess the associations of oral anticoagulant use with the risk of 28-day mortality and in-hospital mortality. Propensity score matching (PSM) was performed in ARDS patients according to whether they were taking oral anticoagulants or not to control potential bias. Subgroup analysis was performed according to severity of ARDS (mild, moderate, and severe), and comorbidities (atrial fibrillation, sepsis, and AKI). Hazards ratio (HR) and respective confidence interval (CI) were presented. In total, 7758 patients not receiving oral anticoagulant and 905 patients receiving oral anticoagulant. The reduced risk of 28-day mortality in ARDS patients was identified in those undergoing oral anticoagulant use (HR = 0.32, 95%CI: 0.24-0.44). Oral anticoagulant use was associated with reduced risk of in-hospital mortality (HR = 0.27, 95%CI: 0.20-0.37). After adjusting for the respective confounding factors, the associations of Warfarin with decreased risk of 28-day and in-hospital mortality were not significant (P > 0.05). Oral anticoagulant was related to decreased risk of 28-day/in-hospital mortality in patients with ARDS. Warfarin and novel oral anticoagulants showed no significant difference on 28-day/in-hospital mortality in patients with ARDS.

BackgroundIn 2022, the American Heart Association launched an updated algorithm for quantifying cardiovascular health (CVH), termed Life’s Essential 8 (LE8). This new approach has been shown to be associated with various noncommunicable chronic diseases and mortality. However, LE8 did not take into consideration the importance of psychological health on CVH. Recently, a perspective article proposed Life’s Crucial 9 (LC9), which would add psychological health as another component to LE8, as a novel metric to assess CVH. This study aims to investigate the association of LC9 with all-cause and cardiovascular disease (CVD) mortality.MethodsThis study included 23,080 adults from National Health and Nutrition Examination Survey 2005–2018, and mortality was ascertained by linkage to National Death Index records through 31 December 2019. The LC9 scoring algorithm was categorized into low (0–49), moderate (50–79), and high (80–100) CVH. Weighted Cox proportional hazards regression models and restricted cubic spline analysis were applied to evaluate the association of LC9 with mortality.ResultsDuring a median follow-up of 7.8 years, a total of 2,388 overall deaths were identified, covering 613 CVD deaths. Compared with adults with a low CVH score, those with a high CVH score had 52% (hazard ratio, 0.48; 95% confidence interval, 0.38–0.60) and 64% (0.36; 0.23–0.56) reduced risk of all-cause and CVD mortality. Similarly, a moderate CVH score was associated with 33% (0.67; 0.58–0.78) and 49% (0.51; 0.40–0.64) reduced risk of all-cause and CVD mortality. The population-attributable fractions of high vs. moderate or low CVH score were 46.0% for all-cause mortality and 75.8% for CVD mortality. Elevated blood lipids, high body mass index, and poor sleep quality were the three major contributors to all-cause mortality, whereas nicotine exposure, unhealthy psychology, and elevated blood lipids were the three significant ones to CVD mortality. There were approximately negative linear dose-response relationships of total LC9 score with all-cause and CVD mortality.ConclusionsAdhering to a high LC9 score is related to a reduced risk of all-cause and CVD mortality. This new CVH definition shows promise as a primordial preventive strategy to reduce mortality rates.

Background/Objectives: Bone metastasis is a common and severe complication of lung adenocarcinoma (LUAD), impacting prognosis and treatment outcomes. Understanding the molecular mechanisms behind LUAD bone metastasis (LUADBM) is essential for developing new therapeutic strategies. The interactions between long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in the competing endogenous RNA (ceRNA) network are crucial in cancer progression and metastasis, but the regulatory mechanisms in LUADBM remain unclear. Methods: Microarray analysis was performed on clinical samples, followed by weighted gene co-expression network analysis (WGCNA) and construction of a ceRNA network. Molecular mechanisms were validated using colony formation assays, transwell migration assays, wound healing assays to assess cell migration, and osteoclastogenesis assays to evaluate osteoclast differentiation. Potential therapeutic drugs and their binding affinities were predicted using the CMap database and Kdeep. The interaction between the small-molecule drug and its target protein was confirmed by surface plasmon resonance (SPR) and drug affinity responsive target stability (DARTS) assays. Mechanistic insights and therapeutic efficacy were further validated using patient-derived organoid (PDO) cultures, drug sensitivity assays, and in vivo drug treatments. Results: Our results identified the XLOC_006941/hsa-miR-543/NPRL3 axis as a key regulatory pathway in LUADBM. We also demonstrated that GATA3-driven Th2 cell infiltration creates an immunosuppressive microenvironment that promotes metastasis. Additionally, we confirmed that the inhibitor E7449 effectively targets NPRL3, and its combination with the IL4R-blocking antibody dupilumab resulted in improved therapeutic outcomes in LUADBM. Conclusions: These findings offer new insights into the molecular mechanisms of LUADBM and highlight potential therapeutic targets, including the XLOC_006941/miR-543/NPRL3 axis and GATA3-driven Th2 cell infiltration. The dual-target therapy combining E7449 with dupilumab shows promise for improving patient outcomes in LUADBM, warranting further clinical evaluation.