BackgroundPerioperative hypoxia remains a common clinical complication. Allogeneic blood transfusion and conventional oxygen support are widely used but limited by blood shortage, supply constraints and ethical challenges. Perfluorocarbon-based oxygen carriers (PFCs) possess superior oxygen solubility and favorable physicochemical features, making promising candidate adjuncts to improve perioperative oxygenation, despite multiple unresolved translational drawbacks.MethodsThis scoping review strictly followed the PRISMA-ScR standard. Six mainstream databases were systematically searched for English human and animal studies published from 2000 to 2025 focusing on perioperative and surgical applications of PFCs; eligible literature was screened and data extracted based on predefined criteria.ResultsA total of 55 publications including 13 randomized controlled trials were enrolled. Preclinical and clinical data demonstrated PFC effectively improves tissue oxygenation and organ protection across hemorrhagic shock, brain injury and acute lung injury, with the most consistent therapeutic gains observed in organ preservation. PFC can reduce allogeneic transfusion requirements during major surgery and benefit cerebral ischemia management, while inflammatory side effects, thrombocytopenia and other adverse reactions have been repeatedly documented.ConclusionPFCs show encouraging tissue-protective effects particularly in organ preservation, yet its broad clinical translation is hindered by inherent limitations such as high oxygen dependence, CARPA, reticuloendothelial deposition and historical failure of classic formulations. Further optimized formulation design and large-scale clinical trials are mandatory to improve safety and realize targeted clinical application.

BACKGROUND:The transfusion of uncross-matched O-type red blood cells(URBCs)is the global standard of care for emergency resuscitation in trauma.However,its application in China remains limited due to concerns over safety and resource availability.This study aimed to evaluate the clinical efficacy and safety of URBCs in patients with severe pelvic fractures. METHODS:In this multicenter,retrospective cohort study(2019-2023),patients with severe pelvic fractures(Abbreviated Injury Scale[AIS]≥3)transfused within 24 h of admission were stratified into the URBC and non-URBC groups.Propensity score overlap weighting(PSOW)was used to address confounding factors.The primary outcome was 30-day in-hospital mortality.Secondary outcomes included length of stay(LOS),24-hour blood product consumption,and in-hospital complications. RESULTS:A total of 526 patients were included(URBC group,n=57;non-URBC group,n=469).After PSOW adjustment,there was no significant difference in 30-day mortality(21.4%vs.21.3%,P=0.989)between the URBC and non-URBC groups.However,the URBC group received significantly lower volumes of plasma,platelets,and cryoprecipitate within the first 24 h(all P<0.05).No clinically significant acute hemolytic transfusion reactions were observed during the study period.Furthermore,subgroup analysis of non-O-type blood recipients(57.1%)showed no significant differences in mortality compared with their O-type counterparts,and no acute hemolytic transfusion reactions were observed. CONCLUSION:Early administration of URBCs for severe pelvic fractures is safe.While not associated with increased mortality or hemolytic transfusion reactions,early use of URBCs was linked to a significant reduction in coagulation-related blood product consumption.This study provides evidence supporting the implementation of URBC within resource-constrained trauma setting to improve resuscitation efficiency.

Hyperkalemia is a common and potentially lethal electrolyte disorder in the emergency department (ED). We aim to explore the real-world effectiveness of hyperkalemia treatment, and the patterns of hyperkalemia management in the ED in China. POETRY-E (ChiCTR2100053100) was a multicenter, prospective, observational study. Adult patients with serum potassium (sK+) ≥ 5.5 mmol/L admitted to the ED were enrolled from 15 centers across China and followed until discharge from the ED. The primary endpoint was the change in sK+ from baseline to 6 h after treatment initiation. Secondary and exploratory endpoints included the clinical burden of hyperkalemia (e.g., severity, complications, survival, etc.), and the real-world management strategies of hyperkalemia in the ED. Between October 2021 and March 2023, 577 patients were enrolled. The median (Q1, Q3) baseline sK+ was 6.25 (5.82, 6.83) mmol/L. At 6 h, after treatment initiation, the median (Q1, Q3) change in sK+ from baseline was − 1.30 (− 1.96, − 0.72) mmol/L (P < 0.001), with 46.4

Cardiac arrest (CA) induces global ischaemia-reperfusion (I/R) injury that results in extensive neuronal damage and high rates of mortality and cognitive impairment, yet effective neuroprotective therapies remain lacking. A major barrier to intervention is the blood-brain barrier (BBB), which restricts drug access to injured brain tissue. Here, we present a BBB-penetrant nanotherapy that combines zwitterionic poly (tertiary amine oxide)-based micelles (OPDEA) with pleiotropic neuroprotectant artesunate (Art). The resulting formulation (OAMs) efficiently crosses the intact BBB via adsorptive-mediated transcytosis and accumulates in hippocampal neurons and microglia. Using in vitro hypoxia-reoxygenation and in vivo male mouse CA/cardiopulmonary resuscitation (CPR) models, we identify haem oxygenase-1 (HMOX1)-mediated ferroptosis as a key mechanism of post-resuscitation neuronal injury. OAMs suppress HMOX1 activity, restore iron homeostasis, and alleviate lipid peroxidation, thereby preserving mitochondrial function and neuronal viability. This work defines the HMOX1-ferroptosis axis as a tractable therapeutic target and positions OPDEA micelles as a BBB-penetrant nanoplatform for neuroprotection after CA and potentially other central nervous system diseases. Limited drug delivery across the blood-brain barrier (BBB) hinders the therapy of post-resuscitation brain injury after cardiac arrest. Here, the authors report zwitterionic poly (tertiary amine oxide)-based micelles that cross the BBB via transcytosis and deliver artesunate to suppress haem oxygenase-1-driven ferroptosis, restore iron homeostasis and provide neuroprotection after resuscitation.

Objective: Emergency medical services (EMSs) management requires maintaining a delicate balance between time, resources, and quality of care. Rapid and effective decision-making is crucial for patient outcomes. Our goal is to integrate advanced large language models (LLMs) into EMS systems to assist in triage decisions and test their practicality and benefits. Methods: This method is designed for emergency triage scenarios. By designing specific prompts to introduce heuristic emergency strategies, it makes full use of the multi-turn dialogue capability and contextual understanding characteristics of LLMs to achieve a comprehensive assessment of the dynamic changes in the condition of the injured and emergency resources. Thus, it forms dynamic triage decisions for a large number of injured people, and can also provide detailed explanations of the decision reasons. This method was evaluated and verified using 4 different LLMs (GPT-4, GLM-4, Qwen-max-0428, and Baichuan2-7b-chat-v1) in various scenarios, including different numbers of injured individuals and various types of large-scale casualty events on our self-built emergency medical dispatch simulation platform, and was compared with the nearest transport method. Additionally, the differences between doctors and LLMs in terms of triage decisions were compared, and emergency experts were invited to evaluate the triage decision results and processes. Results: We conducted experiments on EMSs under 6 different resource environment conditions. With comprehensive patient information and hospital treatment capacity information, GLM-4, GPT-4, and Qwen-max-0428 demonstrated decision-making capabilities far surpassing traditional evacuation methods. GLM-4 and Qwen-max-0428 improved survival rates by an average of 15% after prompt optimization, whereas GPT-4 performed even better, with an average improvement in survival rates reaching 23% after prompt optimization. The consistency level of manual controlled trials (as high as 0.67) reveals that LLMs have guiding and training significance for inexperienced triage personnel in making triage decisions. However, in clinicians’ evaluations, it was revealed that LLMs possess good decision-making abilities, but there is still scope for improvement compared to the level of emergency experts. Conclusion: This study highlights the potential of LLMs in EMS diversion decision-making and suggests that more comprehensive emergency information can further enhance their decision-making abilities.

BACKGROUND: The brain energy crisis following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) is a major contributor to poor neurological outcomes. While lactate is traditionally viewed as a metabolic byproduct, its potential as an alternative metabolic substrate and as a signaling molecule remains controversial. This study investigates whether exogenous lactate administration (ELA) mitigates post-cardiac arrest brain injury (PCABI) and explores the underlying mechanisms. METHODS: A rat model of CA/CPR and HT22 neurons subjected to oxygen-glucose deprivation/reoxygenation were employed. Multi-omics profiling, metabolic flux analysis, immunofluorescence, transmission electron microscopy, co-immunoprecipitation, and gene knockdown, were employed to dissect the underlying mechanisms. RESULTS: ELA significantly improved 5-day survival, neurological function, and neuronal integrity in CA/CPR rats. Metabolomic and proteomic analyses revealed that ELA reprogrammed energy metabolism by alleviating the post-ischemic glycolytic surge, enhancing electron transport chain activity, and restoring the ATP/ADP ratio. In vitro, ELA’s neuroprotection was dependent on its cellular uptake and metabolic utilization, improving mitochondrial function, and reducing oxidative stress. Transcriptomic and ultrastructural analyses identified that ELA potently suppressed pathological mitophagy. Mechanistically, ELA promoted FOXO3A lactylation, thereby preventing its nuclear translocation and promoting its cytoplasmic retention and degradation. Consequently, the mitophagy receptor BNIP3 expression was downregulated, thereby inhibiting excessive mitophagy. The anti-mitophagic effect of ELA was abrogated following genetic ablation of Crebbp, an enzyme reported with lactyltransferase capability. CONCLUSION: Our findings demonstrate that ELA alleviates PCABI by dually reprogramming energy metabolism and suppressing pathological mitophagy. These results position lactate not only as a metabolite intermediate but also as a potential therapeutic agent and signaling molecule in PCABI.

Agitation is a common and clinically significant problem in critically ill patients, closely associated with unplanned extubation, device removal, prolonged hospital stay, and increased mortality. Traditional assessment tools such as the richmond agitation-sedation scale (RASS) and sedation-agitation scale (SAS), despite their widespread use, are limited by intermittent assessment, subjectivity, and inability to provide continuous monitoring. In recent years, the rapid development of artificial intelligence and sensing technologies has opened new avenues for objective, continuous, and real-time agitation monitoring through vital sign-based parameters, video surveillance with computer vision, wearable devices, and multimodal fusion approaches. This narrative review systematically examines the epidemiological characteristics and clinical consequences of agitation in critically ill patients, analyzes the limitations of traditional assessment tools, and highlights emerging technologies based on physiological signals, computer vision, deep learning, and multimodal integration. The current status and challenges of agitation monitoring in various clinical settings—including intensive care units, emergency departments, prehospital environments, and inter-hospital transport-are discussed. Finally, future directions for multimodal early warning systems in complex environments are proposed, providing a theoretical foundation for constructing a comprehensive agitation monitoring system spanning prehospital, in-hospital, and transport settings based on vital signs and video-based behavioral analysis.

Cardiac arrest-induced brain injury significantly affects patient prognosis, yet effective therapeutic strategies remain lacking in clinical practice. In recent years, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have garnered considerable attention for their notable neuroprotective potential. However, studies in cardiac arrest models remain relatively limited. This study aimed to investigate the protective effects and underlying mechanisms of human embryonic stem cell-derived mesenchymal stem cell extracellular vesicles (hESC-MSC-EVs) against brain injury following cardiac arrest/resuscitation (CA/CPR). In vivo, a rat model of cardiac arrest was established by asphyxia, and hESC-MSC-EVs were administered intravenously after resuscitation. In vitro, HT22 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). The results demonstrated that hESC-MSC-EVs significantly improved neurological function at 24 h post-resuscitation, reduced serum levels of NSE and S100B, alleviated pathological damage, and inhibited apoptosis in the hippocampal CA1 region at 7 days after resuscitation. In vitro experiments further confirmed that hESC-MSC-EVs increased HT22 cell viability, reduced reactive oxygen species levels, and suppressed apoptosis. Further mechanistic investigation revealed that hESC-MSC-EVs significantly attenuated pyroptosis in HT22 cells and rat hippocampal neurons, and suppressed the expression of cGAS/STING pathway-related proteins. Activation of the cGAS/STING pathway exacerbated OGD/R-induced HT22 cell injury and CA/CPR-induced brain injury, whereas hESC-MSC-EVs intervention effectively reversed these effects. Mechanistically, miR-181a-5p was identified to target and inhibit Cgas and transfection with miR-181a-5p mimics downregulated the cGAS/STING signaling pathway and alleviated pyroptosis in HT22 cells. Collectively, hESC-MSC-EVs ameliorate brain injury following CA/CPR by inhibiting cGAS/STING-mediated neuronal pyroptosis, offering novel potential therapeutic targets and strategies for clinical management.

Post-resuscitation brain injury is the main contributor to the death and disability of cardiac arrest (CA) victims. Neuronal ferroptosis is involved in the pathogenesis of brain injury after resuscitation, which becomes an effective therapeutic target. Recent studies demonstrated that mesenchymal stem cell-derived exosomes (MSC-Exo) were a promising approach for the alleviation of regional cerebral ischemia reperfusion injury; however, its effectiveness in post-resuscitation brain injury remains to be investigated. In this study, we investigated whether MSC-Exo could alleviate post-resuscitation brain injury by inhibiting neuronal ferroptosis and its regulatory mechanism. In vivo, a clinically relevant swine model of CA and resuscitation was established. In parallel, SH-SY5Y neuronal cells exposed to hypoxia/reoxygenation (H/R) were used as the in vitro model. We found that MSC-Exo administration provided potent protection of neuronal cells against H/R injury in vitro, and effectively alleviated brain injury after CA and resuscitation in vivo. Furthermore, we showed that the protective effects of MSC-Exo administration were associated with the upregulation of protein arginine methyltransferase 1 (PRMT1), solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, and subsequent inhibition of neuronal ferroptosis in in vitro and in vivo studies. Mechanistically, MSC-Exo administration promoted the recovery of PRMT1 expression, and then the latter bound to the promoter of SLC7A11 and enhanced its transcriptional activity after H/R injury in neuronal cells. Additionally, the miR-320a-3p/tripartite motif-containing 21 (TRIM21) axis was a possible mechanism by which MSC-Exo administration activated the PRMT1/SLC7A11/GPX4 pathway in vitro. MSC-Exo administration effectively alleviated post-resuscitation brain injury after CA and resuscitation, which was related to the inhibition of neuronal ferroptosis partly through the activation of PRMT1/SLC7A11/GPX4 pathway.

BackgroundThe global burden of injury is a key indicator for assessing public health and medical needs. During the COVID-19 pandemic, this burden was impacted. This study aims to explore how the pandemic influenced the injury burden globally and regionally, and provide recommendations to relieve this burden.MethodsThe burden of injury-related data is derived from the Global Burden of Disease (GBD) 2021 Study. Autoregressive integrated moving average (ARIMA) and ARIMA-Long short-Term Memory (LSTM) models were adopted for counterfactual inference to predict the scenario without the pandemic.ResultsDuring the COVID-19 pandemic, the observed global age-standardized incidence rate (ASIR) of injury exceeded the predicted value by 107.31 per 100,000, and the observed age-standardized prevalence rate (ASPR) was higher than the predicted value by 102.81 per 100,000. Self-harm and interpersonal violence saw the largest deviations above predicted values in Europe and parts of Asia. Specifically, Armenia's ASIR was 7,829.33 per 100,000 higher than predicted, and its ASDR exceeded projections by 5,186.32 per 100,000. Besides, traffic injuries exceeded predicted levels most significantly in Southeast Asia, with Indonesia's ASIR 25.48 per 100,000 higher than projected. And the observed ASIR of unintentional injuries in China was 379.61 per 100,000 higher than the predicted value.ConclusionDuring the COVID-19 pandemic, the global burden of injuries surpassed the predicted levels for a scenario without the pandemic in 2020-2021, especially in Europe and Asia. In addressing an epidemic, prevention and emergency measures for high-burden injury types and key populations should be strengthened based on local socio-cultural contexts.

Discomfort of noninvasive respiratory supports remain controversial. In the present study, the discomfort of high flow nasal cannula oxygen, noninvasive ventilation, and conventional oxygen therapy were evaluated in the post-extubation period. Noninvasive ventilation alternating with high flow nasal cannula oxygen or conventional oxygen therapy were implemented for 48 h following extubation in patients free of chronic obstructive pulmonary disease. Using a 10-cm visual analog scale, the discomfort of the interface (oxygen mask, nasal prongs or facial mask), was self-evaluated by 264 patients after extubation whereas the discomfort of the respiratory support (conventional oxygen therapy or high flow nasal cannula oxygen alternating with noninvasive ventilation) was evaluated by the nurses in 306 patients. Evaluations were performed in patients at high (n = 127) and low (n = 179) risk of postextubation respiratory failure, 6, 24 and 48 h after extubation. Facial mask was the source of a significant and persisting self-evaluated discomfort. Nasal prongs and oxygen mask were less uncomfortable, with a progressive reduction of the discomfort with time. High flow nasal cannula oxygen alternating with noninvasive ventilation caused a significant and persisting nurse-reported discomfort. Conventional oxygen therapy was significantly less uncomfortable, and the degree of discomfort was not different in patients at high and low risk of extubation failure. Noninvasive ventilation was associated with a significant and persisting discomfort whereas high flow nasal cannula oxygen-induced discomfort remained limited. After 48 h, discomfort resulting from high flow nasal cannula oxygen and conventional oxygen therapy was similar and negligible.

Takotsubo syndrome (TTS),also known as stress-induced cardiomyopathy,presents clinical manifestations similar to acute coronary syndrome (ACS).[1]Accurate and timely differentiation is crucial in emergency settings. Paraganglioma is a rare neuroendocrine tumor originating from extra-adrenal chromaffin tissue. It is characterized by excessive catecholamine secretion,which can lead to severe hemodynamic and metabolic disturbances. We herein report a case of TTS complicated by cardiac shock caused by paraganglioma. Following mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation (V-A ECMO)and appropriate preoperative management,the patient underwent successful tumor resection and achieved full recovery.

ObjectiveMedical domain large language models (LLMs) exhibit verified clinical decision-support capabilities in simulated case analyses and standardized tests, yet their diagnostic efficacy in real-world emergency settings remain insufficiently explored. This study evaluates the diagnostic performance of 5 mainstream LLMs (ChatGPT-4o, Gemini-2.0, Grok3, DeepSeek-V3, Doubao) against emergency department junior physicians (EDJP) on real-world emergency internal medicine cases.MethodsA single-center retrospective analysis design was conducted. 154 anonymized emergency internal medicine patients of the Second Affiliated Hospital of Zhejiang University School of Medicine from January to May 2025 were included, covering common acute diseases of multiple systems. 15 EDJPs and 5 LLMs were selected to diagnose the cases, respectively. The main diagnostic accuracy, comprehensiveness of differential diagnosis, and response time were used as evaluation indicators. Non-parametric tests were used for statistical analysis.Results(1) Main diagnostic accuracy: DeepSeek-V3 (90.0%), ChatGPT-4o (86.0%), and Grok3 (86.0%) were significantly higher than that of EDJP (77.5%, p < 0.05); in the subgroup of respiratory system diseases, Gemini-2.0 and DeepSeek-V3 performed better (p < 0.05). (2) Comprehensiveness of differential diagnosis: The scores of all LLMs were significantly higher than that of EDJP (p < 0.05), and the medians of DeepSeek-V3, Gemini-2.0, and Grok3 reached 5.0 points. (3) Response time: LLMs (6.3–14.0 s) were significantly faster than EDJP (360.2 s, p < 0.05), and Doubao had the fastest response. The inter-rater reliability was good (ICC: 0.617–0.899).ConclusionThis retrospective study shows that LLMs outperformed EDJPs in diagnostic accuracy, differential diagnosis comprehensiveness and response efficiency for emergency internal medicine diseases, demonstrating significant potential for clinical decision support. Subsequent efforts will focus on exploring how to effectively integrate into physician-led collaborative workflows to enhance emergency care quality and efficiency.

Cardiac arrest (CA) is a leading cause of death globally. Exosomes derived from mesenchymal stem cells exhibit favourable production, storage, and safety characteristics, making them a promising alternative for post-CA resuscitation. We assessed the safety, biodistribution, and protective effects of human embryonic stem cell-derived immunity-and-matrix regulatory cells (hESC-IMRC-Exo) for post-CA resuscitation cardiac/cerebral injuries, and preliminarily explored its underlying molecular mechanism. The biotoxicity of IMRC-Exo was evaluated in AC16 and HT22 cells and in mice; its biodistribution was traced using fluorescently labelled IMRC-Exo. Protective effects were examined in H/R-treated cells and rat and swine CA models. We found that IMRC-Exo did not induce apoptosis or oxidative stress in AC16 or HT22 cells. IMRC-Exo was also safe in mice, with normal body weight, blood indices, and histopathology. Pharmacokinetic analysis revealed rapid multi-organ distribution, peaking at 24 h with a 7-day half-life. For efficacy study, IMRC-Exo reduced LDH release, ROS levels, and apoptosis in H/R-treated cells. In rat, IMRC-Exo dose-dependently (0.5×, 1×, 2×) reduced serum biomarkers, improved neurological function, and attenuated inflammation. In swine, single-dose IMRC-Exo (1×) reduced injury biomarkers, improved neurological function, and attenuated inflammation. Furthermore, in a separate rat group, IMRC-Exo improved 7-day survival and neurological function. Mechanistically, the protective effects of IMRC-Exo were mediated by its secreted miR-21-5p, which attenuated H/R-induced apoptosis and inflammation by targeting PDCD4. This study demonstrated IMRC-Exo, a safe and effective therapeutic, distributed rapidly via the bloodstream to target organs and protected against post-resuscitation cardiac/cerebral injuries, potentially through the miR-21-5p/PDCD4 axis.

OBJECTIVE:To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS:Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×106/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS:The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS:Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.

BACKGROUND:Internal iliac artery embolization (IIAE) is a critical hemostatic intervention for controlling hemorrhage in patients with hemodynamically unstable pelvic fractures (HUPF). However, the optimal technique-nonselective versus selective embolization-and the choice of embolic materials remain debated. This study compares the efficacy, safety, and clinical outcomes of nonselective embolization (NSE) and selective embolization (SE) techniques in patients with HUPF. A secondary analysis examined the impact of different embolic materials on patient outcomes. METHODS:This multicenter retrospective study included patients aged 16 and older with HUPF who underwent IIAE. Patients were categorized into NSE or SE groups. Key outcomes included 24-h red blood cell (RBC) transfusion volume, duration of angioembolization (AE), complications, mortality, and infection rates. Propensity score overlap weighting (PSOW) was used for comparisons, with validation via propensity score matching (PSM). Subgroup analyses also employed PSOW to assess outcomes based on embolic materials. RESULTS:A total of 296 patients with HUPF met the inclusion criteria, with 214 undergoing NSE and 82 receiving SE. After PSOW, near-perfect comparability between the two groups was achieved (SMDs = 0). The NSE group had significantly lower 24-h RBC transfusion volumes (2.00 vs. 4.00 units, MD, -2 units; 95% CI, -2.0 to 0; and p = 0.018) and shorter AE duration (65 vs. 80 min, MD, -15 min; 95% CI, -20 to -5.16; and p < 0.001). NSE group also required less 24-h plasma transfusion. Although the NSE group showed higher rates of deep vein thrombosis and urinary tract infection in PSOW analysis, subsequent PSM analysis revealed no significant differences between groups. Similarly, both groups showed comparable rates of other complications, hospital costs, and mortality rates. Subgroup analysis showed that the gelatin sponge (GS) group had higher 24-h RBC transfusion volumes and longer AE durations, though these were not statistically significant. Notably, the GS group had significantly higher rates of pulmonary infections and incision/pin tract infections. CONCLUSION:Nonselective embolization appeared to be associated with reduced RBC transfusion needs and provide faster hemorrhage control, though this did not translate to a survival benefit. The evidence regarding NSE's effect on specific complication risks was inconclusive. Subgroup analysis showed coils were associated with fewer complications than GS. Further prospective studies are needed to clarify the optimal technique and materials.

Cerebral injury after cardiac arrest (CA) is a frequent cause of death and diminished quality of life among patients who have successfully undergone cardiopulmonary resuscitation (CPR); however, treatment options remain limited. Artesunate (Art), primarily an antimalarial compound with well-documented anti-inflammatory properties, has also demonstrated efficacy in mitigating ischemia-reperfusion injury. Herein, we explored the role of Art in mitigating cerebral injury after CA and its potential mechanisms. In vivo models of CA/CPR were established in mice via potassium chloride injection and in swine via electrical stimulation. For the in vitro experiments, a cell model was created by subjecting Neuro-2a cells to hypoxia/reoxygenation (H/R). Knockdown of NEDD4 was achieved through infection with adeno-associated virus or small interfering RNA. After treatment with Art, a series of methods were employed to evaluate neurological function, cerebral injury severity, cell pyroptosis, and neuroinflammatory responses. Art markedly improved neurological function, reduced neuronal death, and attenuated the inflammatory response following CA, and these therapeutic effects were linked to the inhibition of neuronal pyroptosis. Further investigations revealed that Art upregulated NEDD4 expression, which enhanced its binding to caspase-11, inhibited the activation of gasdermin D (GSDMD), and thereby suppressed caspase-11/GSDMD-mediated pyroptosis. Notably, knockdown of NEDD4 increased the ubiquitination of caspase-11 and reversed the neuroprotective effect of Art under both H/R and CA/CPR conditions. Overall, Art effectively ameliorated cerebral injury following CA, with the associated mechanism potentially involving the inhibition of caspase-11/GSDMD-mediated pyroptosis via the upregulation of NEDD4.

Brain injury following cardiac arrest (CA) is a significant cause of mortality and poor prognosis in patients, and effective treatment strategies remain limited. Stem cell-derived extracellular vesicles (EVs), a novel cell-free therapeutic approach, have recently demonstrated significant potential in the field of brain injury repair. EVs, key mediators of stem cell paracrine and autocrine signaling, are enriched with bioactive molecules such as non-coding RNAs and proteins. These EVs have the capacity to traverse the bloodstream, reach injury sites, and modulate various biological processes, including neuronal survival, oxidative stress, inflammatory responses, blood-brain barrier integrity, and neurovascular regeneration.This review aims to provide a comprehensive overview of the research history, structural characteristics, and in vivo distribution and metabolism of stem cell-derived EVs. The review further explores their therapeutic potential and underlying mechanisms in post-CA brain injury, including the inhibition of neuronal apoptosis, alleviation of oxidative stress and inflammation, promotion of blood-brain barrier repair, and enhancement of neurovascular regeneration. Additionally, the review highlights emerging directions and challenges in the clinical application of stem cell-derived EVs, offering theoretical insights and perspectives for future research and translational development. The potential of stem cell-derived EVs as a breakthrough strategy for treating post-CA brain injury is underscored, offering renewed optimism for enhancing patient outcomes.

AIMS:Post-cardiac arrest brain injury (PCABI) is a leading cause of death in cardiac arrest/cardiopulmonary resuscitation (CA/CPR) victims and long-term disability in CA/CPR survivors. Despite previous evidence indicating that the microbiota-gut-brain axis is critically involved in many neurological disorders, no research has hitherto established a connection between the gut microbiota and PCABI through this axis. This study aims to explore the biological roles of microbial tryptophan metabolites in the progression of PCABI. METHODS:To achieve this, we pretreated rats with a cocktail of broad-spectrum antibiotics (Abx) to eradicate the gut microbiota before establishing a 7-min asphyxia-CA/CPR model. RESULTS:Remarkably, the 24-h survival rate and neurological outcomes improved in Abx/CPR rats. Fecal 16s rDNA sequencing and PICRUSt2 analysis revealed that Abx reshaped the microbial community and elevated the proportion of microbial tryptophan metabolism in rats. Metabolomic profiling suggested that Abx shifted the phenotype of microbial tryptophan metabolism from the indole pathway to the kynurenine pathway, thereby increasing the levels of the neuroprotective metabolite kynurenine in the feces, circulation, and ultimately the brain. Furthermore, the hippocampal expression of aryl hydrocarbon receptor (AhR), an endogenous receptor of kynurenine, was upregulated in Abx/CPR rats. In vitro experiments further demonstrated that the neuroprotective effects of kynurenine are AhR-dependent and that AhR activation could negatively regulate the NLRP3 protein expression. Supporting this, results from qRT-PCR, immunohistochemistry, and immunofluorescence in the rat cerebral cortex exhibited that L-kynurenine inhibited NLRP3-induced pyroptosis. CONCLUSIONS:Our study provides a direct clue to the essential participation of the microbiota-gut-brain axis in the progression of PCABI. It demonstrates that kynurenine might attenuate PCABI by inhibiting NLRP3-induced pyroptosis.

Brain injury is a common sequela following cardiac arrest (CA), with up to 70