Abstract:The antiphospholipid syndrome (APS) is a complex autoimmune disease that causes a state of hypercoagulability that can result in recurrent venous and arterial thromboses. APS may lead to cardiac manifestations requiring cardiac surgery with cardiopulmonary bypass (CPB). Perioperative anticoagulation management in APS patients is complex. This complexity arises from both the prothrombotic nature of APS and the interference of antiphospholipid antibodies (aPLs) with phospholipid-dependent coagulation assays like activated clotting time. Given that current literature on CPB management in APS patients is largely limited to isolated case reports and lacks a comprehensive synthesis, this review summarizes the cardiac manifestations of APS, challenges posed by CPB, and current strategies for intraoperative anticoagulation management, including heparin dosing, anticoagulation monitoring methods, and protamine reversal practices. We further highlight gaps in evidence and propose a practical three-category framework for managing aPL-positive patients undergoing CPB.

Pipeline inspection is essential for maintaining the safety of critical infrastructure, but manual inspection is dangerous and inefficient, and existing robotic solutions struggle to handle curved and constrained surfaces. Traditional planning methods are either computationally expensive or prone to redundancy and discretization artifacts. To address these challenges, this paper proposes a centerline-aligned Frenet graph framework for surface-based path planning in pipeline environments. By embedding the pipeline surface into a structured two-dimensional manifold passing through the pipeline's central axis, the framework enables efficient heuristic search while maintaining geometric consistency. By combining quadratic programming with kinematic limits, an initial geodesic constrained path is generated and optimized, resulting in a smooth and executable trajectory. Extensive experiments on pipelines with sharp bends, intersections, and real-world pipeline environments demonstrate significant improvements in computational efficiency, path quality, and robustness compared to traditional methods.

Spinal cord injury (SCI) is a severe central nervous system disorder characterized by irreversible damage and lifelong disability, with few effective treatment options. Tetramethylpyrazine (TMP), a bioactive compound from Ligusticum wallichii, has shown promise in SCI therapy. However, its clinical use is limited by poor water solubility, a short half-life, and restricted blood-spinal cord barrier penetration. To address these challenges, a novel self-assembling hydrogel (GAT-H) was developed, utilizing the amphiphilic nature of glycyrrhizic acid (GA) to encapsulate TMP through non-covalent interactions. This environmentally friendly, crosslinker-free formulation produces a uniform, injectable hydrogel with a porous microstructure that matches the mechanical stiffness of spinal cord tissue. It exhibits shear-thinning and self-healing properties, enabling minimally invasive, in situ gelation at irregular lesion sites. Mechanistic studies showed that GAT-H ensures sustained TMP release, inhibiting neutrophil extracellular trap (NET) formation and subsequently blocking the NET-activated cGAS/STING pathway in microglia, which attenuates NLRP3 inflammasome-mediated pyroptosis. Functional assessments revealed significant motor recovery improvements, as indicated by gait analysis. These results position GAT-H as a promising therapeutic platform that combines GA-based self-assembly with TMP’s therapeutic efficacy, offering a preclinical basis for the use of natural product-based hydrogels in SCI treatment.

Emerging SARS‑CoV‑2 variants and related zoonotic sarbecoviruses rely on ACE2 for cell entry, motivating host‑directed antivirals that block spike-ACE2 interaction. Here, we characterize MB‑32, a benzothiazole small molecule that binds ACE2, selectively disrupts binding of SARS‑CoV‑2 spike receptor‑binding domain to ACE2, and preserves ACE2 enzymatic activity across species. MB‑32 potently inhibits entry of SARS‑CoV‑2 variants, SARS‑CoV‑1 and diverse bat/pangolin sarbecoviruses in ACE2‑expressing cells, while sparing vesicular stomatitis virus and authentic MERS‑CoV, indicating non‑virucidal, ACE2‑focused activity. Biochemical and biophysical analyses, supported by ACE2 mutagenesis, support a model in which MB‑32 engages a non‑catalytic surface pocket on the ACE2 N‑terminal helix to allosterically disrupt spike attachment. Intranasal MB‑32 achieves high airway concentrations, protects male ACE2‑transgenic mice and hamsters from SARS‑CoV‑2 disease, and prevents contact transmission of Omicron‑lineage viruses without detectable cardiovascular toxicity. These findings establish MB‑32 as a host‑targeted ACE2 entry inhibitor and provide a framework for small‑molecule ACE2‑directed antivirals against current and future sarbecovirus spillovers.

Therapeutic resistance remains a prevalent and intractable clinical challenge across a broad spectrum of human malignancies. Despite extensive investigations, the intricate molecular networks by which the tumor microenvironment (TME) mediates such resistance are not fully understood. In this study, we identified nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2) as pivotal regulators of adaptive resistance to diverse antitumor therapies, including immune checkpoint blockade (ICB), adoptive T-cell therapy, and cytotoxic chemotherapy. In murine tumor models, genetic ablation of NOD1/2 or receptor-interacting protein kinase 2 (RIPK2), as well as pharmacological inhibition of RIPK2, remodeled the TME by decreasing immunosuppressive macrophages and boosting CD8⁺ T cell infiltration and cytotoxicity. Mechanistically, NOD1/2 activation in macrophages upregulated programmed death-ligand 1 (PD-L1) expression via the RIPK2/NF-κB signaling axis, establishing an immunosuppressive TME that impaired CD8⁺ T cell-mediated antitumor immunity. Notably, in the clinically relevant setting of immunotherapy resistance, targeted suppression of NOD1/2 signaling in patient-derived peripheral blood mononuclear cells (PBMCs) restored and potentiated ICB responsiveness in patient-derived tumor organoids. Bioinformatic analyses further demonstrated that NOD1/2-associated gene signatures were significantly enriched in tumor-associated macrophages post-therapy. Our findings define NOD1/2 as a novel innate immune checkpoint that orchestrates therapy-induced adaptive resistance and highlight this pathway as a promising target to overcome treatment resistance in refractory cancers.

Perioperative red blood cell (RBC) transfusion remains common in cardiac surgery and is associated with increased morbidity and mortality. Accurate preoperative risk prediction is essential for patient blood management. The Fuwai-transfusion risk of on-pump cardiac surgery (FW-TRIC) score was previously developed and internally validated as a tool to estimate transfusion risk. This study aimed to externally validate the FW-TRIC score in a multicenter cohort. A retrospective multicenter study was conducted across nine cardiovascular centers in China from January to December 2024. Adult patients undergoing on-pump cardiac surgery were included, while those undergoing transplantation, mechanical circulatory support, or preoperative transfusion were excluded. The discriminative performance of the FW-TRIC score was evaluated using receiver operating characteristic (ROC) curve analysis, and calibration was assessed through linear regression of observed versus predicted transfusion rates. A total of 3,287 patients met inclusion criteria, with an overall perioperative RBC transfusion rate of 40.1

Severe hyperoxia during venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been associated with adverse clinical outcomes in observational studies. However, causal evidence and optimal oxygen targets remain uncertain. Hyperoxia may exacerbate oxidative stress and organ injury, particularly in the presence of systemic inflammation and ischemic shock. This study aimed to investigate the dose-dependent effects of membrane lung sweep oxygen fraction (FsO₂) during the early phase of VA-ECMO on systemic oxidative stress and early multi-organ injury markers, and to explore the mechanistic role of reactive oxygen species (ROS) using a rat VA-ECMO model. In this randomized experimental study, Sprague–Dawley rats were divided into normal rats and rats with cardiogenic shock induced by septic cardiomyopathy using LPS. Graded membrane FsO2 levels of 30

Continuous-flow left ventricular assist devices (CF-LVAD) have been increasingly implemented in China as a vital life-support strategy for patients with end-stage heart failure. Non-pulsatile blood flow is a defining physiological characteristic of CF-LVAD. Although an association between reduced pulsatility and adverse outcomes continues to be proposed, robust clinical evidence remains lacking. Retrospective study of adults (>18 years) receiving CF-LVAD at four Chinese centers (Jan 2019 - Jul 2024) was conducted. Systemic pulsatility index (SPI, calculated as pulse pressure divided by the mean arterial pressure) was derived from blood pressure measurements pre-LVAD and serially post-LVAD (days 1,7,14,21,28). Latent Class Trajectory Modeling (LCTM) identified distinct population groups based on SPI trajectories. The primary outcome of this study was major adverse events (MAE) within 90 days, including all-cause mortality and complication events. The secondary outcome was the evaluation of each complication event, mortality, ICU and hospital-free days. Among 115 LVAD patients (mean age 49.4 years, 87.8

Background:Macrophage polarization, which affects the lung cancer tumor microenvironment and treatment response through M1/M2 phenotypic transformation, has become a key research area. However, there is a lack of systematic bibliometric analysis. Therefore, this study employed bibliometric methods to comprehensively review the research trends and hotspots in this field. Methods:A comprehensive search was conducted using the Web of Science Core Collection (WoSCC) and Scopus databases for English-language literature published between January 1, 2010, and August 1, 2025. A multidimensional visual analysis of nations, institutions, authors, journals, references, and keywords was performed on the 508 included articles utilizing bibliometric tools VOSviewer, CiteSpace, and Bibliometrix. Results:The number of publications in this field shows an upward trend. From 2010 to 2016, it was in the initial growth stage; from 2017 to 2021, it entered a period of steady growth. After 2022, research activities increased significantly and reached a peak in 2025 (n=131). Frontiers in Immunology (n=25) had the highest number of publications, while Nature Nanotechnology (1,299) had the highest co-citation frequency. Wang Yi-Ching (n=5, H-index =4) and Yang Bo (n=4, H-index =4) are the core authors representing the development of this discipline. China (n=370) has the largest number of publications, and representative institutions include Fudan University (n=19), Chinese Academy of Medical Sciences (n=15), and Shanghai Jiao Tong University (n=14). The USA (94.65) demonstrates the most significant academic influence. Research hotspots have gradually shifted from the correlation between the early macrophage polarization phenotype and the pathological characteristics of lung cancer to molecular mechanisms such as signaling pathways, metabolic reprogramming, and exosomes, and have further expanded to the directions of nanoparticle targeted delivery and clinical translation of immune checkpoint inhibitors. Conclusions:The research in this field has advanced from phenotypic description to mechanism integration and translational research, with nano-intervention and immune regulation being the cutting-edge directions. In the future, attention should be focused on the clinical translation pathways of personalized regulation strategies.

Objective:To externally validate previously published prognostic models developed exclusively from pre-extracorporeal cardiopulmonary resuscitation (ECPR) variables in a contemporary ECPR cohort. Methods:We conducted a bicenter retrospective external validation of four published pre-ECPR prognostic models (Lee, RESCUE-IHCA, CHIU-S1, and CHIU-S2) in adult patients treated with ECPR between January 2015 and December 2024. Model performance was evaluated for in-hospital survival and favorable neurological outcome (FNO; Cerebral Performance Category 1-2) in the overall cohort, in-hospital cardiac arrest (IHCA), and cardiac-origin cardiac arrest (Cardio_CA) subgroups. Discrimination (the area under the receiver operating characteristic curve, AUROC), calibration, overall model fit (Brier score), and decision curve analysis (DCA) were assessed. For point-based CHIU scores, validation focused on observed outcome rates across predefined risk strata. Results:Among 214 patients, 79.0% (169/214) had IHCA; survival to discharge was 45.8% and FNO occurred in 24.8%. Discrimination for survival was modest across models (overall ECPR AUROC 0.608-0.709; IHCA 0.586-0.672; Cardio_CA 0.591-0.689) but was higher for FNO (overall ECPR 0.709-0.764; IHCA 0.696-0.744; Cardio_CA 0.698-0.718). The Lee model showed poor calibration with slopes far below 1, whereas RESCUE-IHCA model underestimated survival but demonstrated better calibration (slopes close to 1), higher overall accuracy (lower Brier scores) and broader clinical utility (wider net-benefit ranges in DCA). CHIU models provided limited risk separation between adjacent strata. Conclusions:In this external validation, pre-ECPR models showed modest performance, with better discrimination for neurological outcome than for survival. RESCUE-IHCA showed the most favorable overall performance. Future studies should develop and validate more robust, transportable tools.

Background Extracorporeal Membrane Oxygenation (ECMO) provides respiratory and circulatory support in patients with severe cardiorespiratory failure. As ECMO technology advances, portability has become an important design consideration for transport and emergency applications. The OASSIST ECMO System is the first portable ECMO system developed in China and has demonstrated satisfactory safety and biocompatibility in preclinical studies. The present study aimed to evaluate its initial clinical safety, efficacy, and device performance in a first-in-human setting. Method From December 2021 to September 2022. This first-in-human study involved 31 patients receiving ECMO support (21 VA-ECMO and 10 VV-ECMO) among 10 medical centers. The study duration was. Primary efficacy endpoints were survival rates at 24hours and 7 days after ECMO weaning, while secondary efficacy endpoints included device performance parameters and necessary patient-level data. The safety endpoints are mainly the monitoring of adverse events related to the test device. Results Baseline demographic characteristics included a mean age of 58.03 ± 15.17 years, and 61.3% male. Mean ECMO support duration was 102.58 ± 89.88hours. Among the 31 patients enrolled, 83.9% (n=26) survived both 24hours and 7 days after ECMO weaning. The VA-ECMO group had a 24-hour and 7-day survival rate of 85.7%, and the VV-ECMO group had 80.0%. 6 (19.4%) patients experienced bleeding events. Oxygenator replacement events were limited to 1 extensive thrombus formation within the oxygenator. There were 19 serious adverse events, including one case of lower limb necrosis that was adjudicated as possibly related to the test device; retrospective review suggested that this event occurred in the setting of pre-existing limb ischemia and may have been aggravated after ECMO cannulation. Performance metrics demonstrated the stable operation of the OASSIST ECMO System, and no major issues with the test device were noted. Conclusion This first in-human, multi-center, clinical trial demonstrated positive outcomes in clinical efficacy and safety of OASSIST ECMO System in providing mechanical cardiopulmonary support in patients cardiorespiratory failure.

We evaluated whether immediate postoperative urine dipstick occult blood after on-pump cardiac surgery could serve as an early indicator of high-risk cardiac surgery-associated acute kidney injury (CSA-AKI). This single-center retrospective study included 11,782 adult patients undergoing elective on-pump cardiac surgery (2018–2024), excluding those with preoperative chronic kidney disease (CKD, stage 3–5), positive preoperative urine occult blood, or postoperative microscopic hematuria. The primary outcome was any-stage CSA-AKI within 7 days after surgery. Multivariable logistic regression was used to evaluate the independent association between immediate postoperative urine occult blood and CSA-AKI. The predictive value was assessed by C-index, the net reclassification improvement index, and integrated discrimination improvement. The goodness-of-fit of models was evaluated through Akaike information criterion, Bayesian information criterion and likelihood ratio test. CSA-AKI occurred in 32.8

Red blood cell distribution width (RDW) is a marker that routinely describes circulating erythrocytes variability and may hold potential prognostic value in cardiac surgery. Our objective is to evaluate the association between peak values of RDW and in-hospital mortality among patients receiving post-cardiotomy veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support. This single-center, retrospective study included adult patients receiving post-cardiotomy V-A ECMO support between January 2017 and December 2024. The association between peak values of RDW and in-hospital mortality was assessed by multivariable logistic regression model. Spearman correlation analysis was used to determine the correlations between related laboratory factors and peak values of RDW. A total of 106 patients were included and in-hospital mortality rate was 54.7

Pericardiectomy is the curative treatment for constrictive pericarditis, yet postoperative low cardiac output syndrome (LCOS) may occur. The application of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in post-pericardiectomy refractory LCOS has limited case reports, and its effectiveness and safety remain unclear. This study aims to provide evidence for the effectiveness of ECMO in treating post-pericardiectomy refractory LCOS. Nine cases of post-pericardiectomy ECMO from two high-volume pericardiectomy centers in China were retrospectively reviewed. Meanwhile, a literature search was performed in PubMed and Embase on December 4, 2024. After screening, 5 articles were finally included for data extraction and comprehensive analysis. Case Series: There were 4 cases of tuberculous etiology, 1 with a history of cardiac surgery, and 4 idiopathic cases. All patients were in New York Heart Association class III - IV at baseline. All the patients undertwent pericardiectomy via median sternotomy, and 5 patients underwent concomitant valve procedures. One patient failed to wean from the cardiopulmonary bypass (CPB) and was transferred to femoral VA-ECMO. Eight patients received femoral VA-ECMO support 4–96 h after surgery due to refractory LCOS. All the patients survived to discharge with good neurological outcomes after 120–192 h of ECMO support. Two patient were lost to follow-up, and the rest 7 patients survived to follow-up with a mean follow-up of 56 months. Literature Review: 4 case reports and 1 retrospective study were identified. In the retrospective study of 69 patients, 8 received ECMO during or after pericardiectomy with a hospital mortality rate of 63

Microorganisms require iron acquisition, particularly in the form of Fe3+ ions from the external environment, for survival. Siderophores are low-molecular-weight compounds secreted by microorganisms that chelate Fe3+ ions and facilitate their transport into cells. This process forms an Fe3+ uptake system in conjunction with specific transporters, enabling microorganisms to meet their iron requirements. A promising strategy involves utilizing the Fe3+ transport mechanism to deliver siderophore-cargo conjugates into microbial cells, thereby enabling the treatment and diagnosis of infectious diseases, including those caused by drug-resistant bacteria. In this perspective, we systematically evaluate each type of siderophore-antibiotic/fluorophore conjugate and its associated therapeutic and diagnostic outcomes. Through this perspective, we aim to further develop the iron uptake strategy as a means to address the increasingly severe global public health challenge of antimicrobial resistance and to achieve rapid and ultrasensitive diagnosis of infections, encompassing but not limited to bacterial and fungal infections.

Postoperative organ dysfunction remains a major challenge in adult cardiac surgery with cardiopulmonary bypass (CPB), frequently involving the kidneys, heart, and lungs. These complications are primarily driven by hemolysis, ischemia-reperfusion injury, and systemic inflammation triggered by CPB. Nitric oxide (NO), known for its vasodilatory, anti-inflammatory, and antioxidant properties, has been proposed as a perioperative strategy to protect vital organs. However, evidence regarding its efficacy remains inconclusive. We followed PRISMA guidelines and systematically searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) published up to March 1, 2025. Subgroup analyses were conducted based on NO dosage and timing of administration. To explore potential effect modifiers and assess subgroup interaction, we performed meta-regression analyses. The GRADE approach was used to assess the certainty of evidence. Sensitivity analyses and publication bias assessments (funnel plots and trim-and-fill method) were also conducted to evaluate the robustness of the findings. Ten RCTs involving 838 patients were included. NO administration was associated with a reduced incidence of acute kidney injury (AKI) (RR: 0.78; 95