ObjectiveConventional left ventricular ejection fraction (LVEF) often fails to detect early sepsis-induced myocardial dysfunction (SIMD). This study aimed to evaluate the prognostic utility of speckle-tracking echocardiography (STE)-derived global longitudinal strain (GLS) and to develop an internally validated clinical nomogram with demonstrated net benefit for predicting 28-day mortality in sepsis patients.MethodsThis prospective observational study enrolled 46 patients presenting with sepsis or septic shock at the Emergency Department of The First Affiliated Hospital of Sun Yat-sen University (February–June 2023). STE-derived average GLS (GLS_AVG), conventional echocardiography, and cardiac biomarkers were evaluated within 24 h of diagnosis. Prognostic performance was assessed using restricted multivariable logistic regression, Receiver Operating Characteristic (ROC) curves, and DeLong's test. A predictive nomogram was constructed, validated via 1,000 bootstrap resamples, and evaluated for clinical utility using Decision Curve Analysis (DCA).ResultsThe 28-day mortality rate was 23.9% (11/46). Compared to survivors, non-survivors exhibited significantly impaired GLS_AVG (−10.09 ± 4.18% vs. −14.69 ± 3.13%, P < 0.001) and higher SOFA scores (11.55 ± 3.11 vs. 7.63 ± 3.15, P = 0.001). GLS_AVG strongly correlated with SOFA (r = 0.663) and NT-proBNP peak (r = 0.424). ROC analysis demonstrated that GLS_AVG (AUC: 0.796) outperformed conventional LVEF (AUC: 0.706) in predicting mortality. The optimal GLS_AVG cutoff was > −11.0% (sensitivity 72.7%, specificity 82.9%). In restricted multivariable analysis, GLS_AVG showed a borderline independent association with 28-day mortality in the restricted multivariable model (OR: 1.266; 95% CI: 0.995–1.676; P = 0.067). The formulated GLS-SOFA nomogram showed excellent calibration upon 1,000-bootstrap internal validation. Crucially, DCA confirmed that integrating GLS yielded a substantially higher clinical net benefit across a wide range of threshold probabilities compared to relying on LVEF alone.ConclusionSTE-derived GLS is a highly sensitive, relatively load-independent marker of early myocardial dysfunction in sepsis, significantly outperforming LVEF in predicting 28-day mortality. The validated GLS-SOFA nomogram and decision curve models provide a practical, high-yield tool to enhance risk stratification and guide early personalized hemodynamic resuscitation in emergency settings.

Background Early recognition of physiological deterioration in surgical intensive care unit (ICU) patients remains challenging. Static snapshots of vital signs fail to capture dynamic trajectory patterns that may harbor prognostic information. We aimed to identify latent physiological trajectory phenotypes using Gaussian Mixture Modeling (GMM) applied to the first 72 hours of bedside monitoring data, and to evaluate their association with disease severity and clinical outcomes. Methods This retrospective cohort study analyzed 3,493 adult ICU patients from a single tertiary-care academic center (2016–2020). Four key physiological dimensions were extracted at hourly resolution over the initial 72 hours post-admission: body temperature (TEMP), central venous pressure (CVP), net fluid balance (FB), and blood glucose (GLU). Principal component analysis (PCA) was applied for dimensionality reduction, followed by GMM clustering with Bayesian Information Criterion (BIC)-optimal model selection. Trajectory phenotypes were characterized by their longitudinal profiles across all four dimensions. Associations with APACHE II scores were assessed via Kruskal-Wallis tests with Dunn's post-hoc comparisons. Fisher's exact tests were used for between-group mortality comparisons, with logistic and Cox regression employed for exploratory prognostic modeling, acknowledging the constraining effect of low overall mortality. Results Five distinct trajectory phenotypes were identified (G1-G5), explaining 83.7% of variance in the first two principal components. Group G2 (n = 338, 9.7%) exhibited the highest APACHE II scores (mean 22.3 +/- 8.5), longest length of stay (median 14.0 days), and the highest mortality rate (1.48%). Group G4 (n = 488, 14.0%) was characterized by advanced age (mean 61.1 years), moderately elevated APACHE II (18.7 +/- 8.0), sustained stress hyperglycemia (mean GLU 8.71 mmol/L), near-zero fluid balance (-0.52 mL/h), and upper-normal CVP (7.09 mmHg)--yet zero deaths were observed in this cluster. APACHE II scores differed significantly across trajectory groups (Kruskal-Wallis H = 231.30, p < 0.0001), with the strongest contrasts between G2 vs. G3 (Z = -13.26, adjusted p < 0.001) and G3 vs. G4 (Z = 8.30, adjusted p < 0.001). Overall mortality did not differ significantly across groups (chi-squared = 8.40, df = 4, p = 0.078). Fisher's exact test showed a borderline trend toward higher mortality in G2 vs. G1 (OR = 2.64, 95% CI not estimable due to low events, p = 0.081). Conclusions GMM-based trajectory phenotyping of early ICU physiological data reveals clinically meaningful patient subgroups with distinct severity profiles and resource utilization patterns. The G4 phenotype–characterized by compensated physiology, advanced age, elevated APACHE II, and prolonged length of stay despite zero observed mortality–may represent a resource-intensive population benefiting from intensified surveillance. Hour-level physiological trajectory analysis offers a complementary dimension to static severity scores and may inform early risk stratification in critical care.

Purpose For patients with suspected fatal high-risk pulmonary embolism (PE) who cannot undergo computed tomography pulmonary angiography (CTPA), should ECMO rescue be prioritized over pulmonary vascular revascularization? What is the optimal revascularization strategy for patients under ECMO? What are the key risk factors affecting prognosis? This study addresses these questions to improve outcomes in high-risk PE. Methods Clinical data of 143 patients with suspected fatal high-risk PE admitted to five ECMO centers (January 2013-January 2024) were retrospectively analyzed. Results 1. Of 143 patients, 79 initially received ECMO (ECMO group), whereas 64 received revascularization (non-ECMO group). The baseline characteristics were similar between the two groups. However, the 28-Day mortality rate was lower in the ECMO group (49.4%, 39/79) than in the non-ECMO group (71.9%, 46/64; P < 0.05). 2. Among 79 ECMO-treated patients, CTPA confirmed PE in 63. Successful ECMO weaning rate was 58.7% (37/63), ECMO duration was 3.7 ± 3.3 days, and the survival to discharge was 54.0% (34/63). 3. Comparisons among ECMO + surgical thrombectomy, ECMO + thrombolysis, and ECMO alone groups showed the lowest 28-Day mortality with ECMO + surgical thrombectomy (9.1% vs 50.0% vs 52.5%, P < 0.05). 4. Logistic Regression Analysis identified the time from shock to ECMO as an independent risk factor affecting prognosis (P < 0.05). Conclusions For patients with suspected fatal high-risk PE, treating the primary disease under ECMO reduces mortality. Surgical thrombectomy may be considered for eligible patients. The time from shock to ECMO is an important factor affecting prognosis in confirmed cases.

Sepsis is a major cause of mortality, particularly in patients with myocardial injury. The objective of this study was to evaluate the impact of dexmedetomidine, propofol, and midazolam on mortality and various outcomes in this population. A retrospective cohort study was performed using the eICU database, encompassing 2,171 septic patients with myocardial injury. Patients were categorized into single- and multiple-sedative groups. The primary endpoint was 100-day mortality, with secondary endpoints encompassing hospital stay, intensive care unit (ICU) stay, mechanical ventilation (MV), and dialysis. Statistical analysis was conducted using Cox regression, Kaplan-Meier curves, and propensity score matching. Among 2,171 patients, dexmedetomidine was associated with lower 100-day mortality in patients with APACHE IV scores < 78.9, particularly in specific subgroups. In patients with APACHE IV scores ≥ 78.9, dexmedetomidine provided no mortality advantage over propofol. Midazolam was linked to higher mortality across all score ranges, and its combination with propofol resulted in worse outcomes compared to dexmedetomidine-propofol. No significant differences were found in hospital stay, ICU stay, or MV rates between the groups. Dexmedetomidine improves prognosis in septic patients with myocardial injury, particularly in those with lower severity of illness, highlighting its potential as a preferred sedative choice in this population.

Objective: To investigate whether the histone deacetylase (HDAC) activator ITSA‐1 can ameliorate systemic inflammation after cardiac arrest (CA), thereby enhancing cardiac function and neurological outcomes in rats. Materials and Methods: Sixty‐nine healthy adult male Wistar rats were subjected to 12 min of CA induced by Vecuronium bromide. The rats were randomly assigned to five groups: normal control, sham operation, control, suberoylanilide hydroxamic acid (SAHA), and ITSA‐1. The study evaluated the effects of ITSA‐1 on cardiac function, survival, and neurological functions, including the neurological deficit score (NDS) at 24‐, 48‐, and 72‐h post‐return of spontaneous circulation (ROSC) and Morris water maze performance at 72 h. Additionally, levels of TNF‐ α , IL‐1 β , glial fibrillary acidic protein (GFAP), S100 β in plasma, and TNF‐ α , IL‐1 β in the hippocampus were measured 4 h post‐ROSC. Western blot analysis was used to assess HDACs, nuclear factor kappa B (NF‐ κ B), p‐NF‐ κ B, caspase‐3, cleaved caspase‐3, Bcl‐2, and Bax protein expressions. Results: ITSA‐1 reduced basic life support (BLS) duration and adrenaline dosage during cardiopulmonary resuscitation (CPR) and improved cardiac and neural functions, enhancing survival compared to the control and SAHA groups. ITSA‐1 decreased serum levels of IL‐1 β , TNF‐ α , GFAP, S100 β , and hippocampal TNF‐ α , IL‐1 β , promoting neuronal survival in the CA1 region. It also inhibited glial cell activation and reduced histone acetylation, blocking the NF‐ κ B pathway and neuronal apoptosis. Conclusion: ITSA‐1 enhances the recovery and survival of post‐ROSC rats by diminishing histone acetylation and mitigating systemic inflammation. This effect is possibly due to the inhibition of glial cell activation, increased neuronal survival in the brain, and improved cardiac output (CO) and ejection fraction (EF).

Background Therapeutic mild hypothermia (MH) is expected to improve the neurological outcome and the survival rate of CPR after cardiac arrest (CA). However, the mechanisms by which MH protects cardiomyocytes remain largely unexplored. Methods In this study, three- to four-month-old male Wistar rats, weighing between 319.1 and 480.0 grams, were randomly divided into normothermia (NT) groups (acceptable range, 36.0-38.0°C) and MH groups (acceptable range, 32-34°C). Ten minutes after CA, CPR was perfumed with a slow injection of 0.30-0.50 mL epinephrine solution (30.00 μg/mL). Moreover, to investigate the role of TRPV1, capsaicin was administered through the right femoral artery in both NT and MH groups. Results We found that MH improved the spontaneous breathing recovery, increased survival rate, and inhibited cardiac necroptosis in Wistar rats after CPR. Additionally, MH alleviated primary cardiomyocytes necroptosis after oxygen-glucose deprivation and reperfusion through upregulating TRPV1, downregulating EGFR, and subsequently suppressing MLKL. Furthermore, the combination of capsaicin, a TRPV1 activator, with MH enhanced blood pressure in Wistar rats after CPR compared to MH alone. Capsaicin improved the spontaneous breathing rate and survival rate of Wistar rats after CPR. Conclusions MH may protect cardiac function by mitigating cardiomyocyte necroptosis through regulating TRPV1.

Astrocytes are abundant glial cells in the central nervous system (CNS) that play important roles in brain injury following cardiac arrest (CA). Following brain ischemia, astrocytes trigger endogenous neuroprotective mechanisms, such as fatty acid transport. Lipid droplets (LDs) are cellular structures involved in neutral lipid storage and play essential roles in many biological processes. However, whether lipid droplet metabolism is related to the neurological prognosis after CA remains unclear. JZL-184 is a selective irreversible inhibitor of monoacylglycerol lipase (MAGL), and previous investigations revealed that JZL-184 confers neuroprotection in the brain following stroke. However, further investigations are warranted to explore the effect and mechanism of JZL-184 after CA. Here, we reveal that JZL-184 is neuroprotective after cardiac arrest, as it alleviates astroglial activation by upregulating the expression of transforming growth factor beta 1 (TGF-β1), promotes the transfer of mitochondria from astrocytes to neurons in the astrocyte‒neuron coculture system, and reduces lipid droplet accumulation in neurons. Mechanistically, this protective effect depends on the downstream genes DUSP4 and Rab27b. This study provides additional insights into strategies for inhibiting neurological impairment and suggests a potential therapeutic target after cardiac arrest.

Immunoregulation is crucial to septic shock (SS) but has not been clearly explained. Our aim was to explore potential biomarkers for SS by pathway and transcriptional analyses of immune-related genes to improve early detection. GSE57065 and GSE95233 microarray data were used to screen differentially expressed genes (DEGs) in SS. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses of DEGs were performed, and correlations between immune cell and pathway enrichment scores were analyzed. The predictive value of candidate genes was evaluated by receiver operating characteristic (ROC) curves. GSE66099, GSE4607, and GSE13904 datasets were used for external validation. Blood samples from six patients and six controls were collected for validation by qRT-PCR and western blotting. In total, 550 DEGs in SS were identified; these genes were involved in the immune response, inflammation, and infection. Immune-related pathways and levels of infiltration of CD4 + TCM, CD8 + T cells, and preadipocytes differed between SS cases and controls. Seventeen genes were identified as potential biomarkers of SS (areas under ROC curves >0.9). The downregulation of CD8A, CD247, CD3G, LCK, and HLA-DRA in SS was experimentally confirmed. We identified several immune-related biomarkers in SS that may improve early identification of disease risk.

Background Adverse left ventricular remodeling after myocardial infarction (MI) compromises cardiac function and increases heart failure risk. Until now, comprehension of the role transcription factor EB (TFEB) plays after MI is limited. Objectives The purpose of this study was to describe the effects of TFEB on fibroblasts differentiation and extracellular matrix expression after MI. Methods AAV9 (adeno-associated virus) mediated up- and down-regulated TFEB expressions were generated in C57BL/6 mice two weeks before the MI modeling. Echocardiography, Masson, Sirius red staining immunofluorescence, and wheat germ agglutinin staining were performed at 3 days, and 1, 2, and 4 weeks after MI modeling. Fibroblasts collected from SD neonatal rats were transfected by adenovirus and siRNA, and cell counting kit-8 (CCK8), immunofluorescence, wound healing and Transwell assay were conducted. Myocardial fibrosis-related proteins were identified by Western blot. PNU-74654 (100 ng/mL) was used for 12 hours to inhibit β-catenin-TCF/LEF1 complex. Results The up-regulation of TFEB resulted in reduced fibroblasts proliferation and its differentiation into myofibroblasts in vitro studies. A significant up-regulation of EF and down-regulation of myocyte area was shown in the AAV9-TFEB group. Meanwhile, decreased protein level of α-SMA and collagen I were observed in vitro study. TFEB didn’t affect the concentration of β-catenin. Inhibition of TFEB, which promoted cell migration, proliferation and collagen I expression, was counteracted by PNU-74654. Conclusions TFEB demonstrated potential in restraining fibrosis after MI by inhibiting the Wnt/β-catenin signaling pathway.

Previous studies have shown that AMPK plays an important role in cerebral ischemia–reperfusion injury by participating in apoptosis, but the exact mechanism and target of action remains unclear. This study aimed to investigate the protective mechanism of AMPK activation on brain injury secondary to cardiac arrest. HE, Nills and TUNEL assays were used to evaluate neuronal damage and apoptosis. The relationships between AMPK, HNF4α and apoptotic genes were verified by ChIP-seq, dual-luciferase and WB assays. The results showed that AMPK improved the 7-day memory function of rats, and reduced neuronal cell injury and apoptosis in the hippocampal CA1 region after ROSC, while the use of HNF4α inhibitor weakened the protective effect of AMPK. Further research found that AMPK positively regulated the expression of HNF4α, and AMPK could promote the expression of Bcl-2 and inhibit the expression of Bax and Cleaved-Caspase 3. In vitro experiments showed that AMPK ameliorated neuronal injury by inhibiting apoptosis through the activation of HNF4α. Combined with ChIP-seq, JASPAR analysis and Dual-luciferase assay, the binding site of HNF4α to the upstream promoter of Bcl-2 was found. Taken together, AMPK attenuates brain injury after CA by activating HNF4α to target Bcl-2 to inhibit apoptosis.

目的:观察组蛋白脱乙酰酶激动剂ITSA-1对心脏停搏心肺复苏后大鼠脑损伤的影响.方法:30只Wistar大鼠,随机分为假手术(sham)组、模型(model)组和ITSA组,每组10只.ITSA组大鼠心脏停搏前3 d连续皮下注射ITSA-1(0.5 mg·kg?1·d?1),sham组和model组给予等体积的生理盐水皮下注射;sham组大鼠在注射肌松药物的同时进行机械通气,model组和ITSA组大鼠在心脏停搏12 min后进行基础生命支持.比较各组大鼠心脏停搏期间的电生理参数及自主循环恢复(ROSC)后血压和72 h生存情况;使用神经功能缺损评分量表(NDS)评估神经功能,采用苏木精-伊红(HE)染色和Nissl染色观察大鼠海马CA1区神经元存活情况;免疫组织化学染色检测海马CA1区胶质细胞原纤维酸性蛋白(GFAP)和离子钙结合接头分子1(Iba-1)的表达;酶联免疫吸附实验检测海马组织中肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)的表达量;Western blot检测海马组织中广谱乙酰化水平及凋亡相关蛋白caspase-3、Bax和cleaved caspase-3的水平.结果:ROSC 72 h后,sham组大鼠存活率为100％,model组为50％,ITSA组为70％.与model组相比,ITSA组大鼠ROSC后72 h存活率和NDS评分均显著升高(P<0.05);海马CA1区的凋亡细胞数量显著减少,存活细胞数量显著增加,GFAP和Iba-1的表达量显著降低(P<0.05);TNF-α和IL-1β表达量及脑组织广谱乙酰化水平显著下降,凋亡相关蛋白caspase3、Bax和cleaved caspase-3水平均显著降低(P<0.05).结论:ITSA-1能够抑制脑组织中胶质细胞激活,从而减轻大鼠ROSC后的脑损伤.

Predicting neurological outcomes after cardiac arrest remains a major issue. This study aimed to identify novel biomarkers capable of predicting neurological prognosis after cardiac arrest. Expression profiles of GSE29540 and GSE92696 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between high and low brain performance category (CPC) scoring subgroups. Weighted gene co-expression network analysis (WGCNA) was used to screen key gene modules and crossover genes in these datasets. The protein-protein interaction (PPI) network of crossover genes was constructed from the STRING database. Based on the PPI network, the most important hub genes were identified by the cytoHubba plugin of Cytoscape software. Eight hub genes (RPL27, EEF1B2, PFDN5, RBX1, PSMD14, HINT1, SNRPD2, and RPL26) were finally screened and validated, which were downregulated in the group with poor neurological prognosis. In addition, GSEA identified critical pathways associated with these genes. Finally, a Pearson correlation analysis showed that the mRNA expression of hub genes EEF1B2, PSMD14, RPFDN5, RBX1, and SNRPD2 were significantly and positively correlated with NDS scores in rats. Our work could provide comprehensive insights into understanding pathogenesis and potential new biomarkers for predicting neurological outcomes after cardiac arrest.

Objective: Critical covid-19 patients have complications with acute myocardial injury is still unclear. We observed a series of critically ill patients, paying particular attention to the impact of myocardial injury at admission on short-term outcome. Methods: We prospectively collected and analyzed data from a series of severe covid-19 patients confirmed by real-time RT-PCR. Data were obtained from electronic medical records including clinical charts, nursing records, laboratory findings, and chest x-rays were from Feb 8, 2020, to April 7, 2020. The Acute Physiology and Chronic Health Evaluation (APACHE II) score, CURB-65 Pneumonia Severity Score, Sequential Organ Failure Assessment (SOFA) Score and pneumonia severity index (PSI) score were made within 24 hours of admission. Cardiac injury was diagnosed as hs-cTnI were above >28 pg/mL. The short-term outcome was defined as mortality in hospital. Results: A total of 100 patients met the diagnostic criteria of severe patients with COVID-19 during 2020.02.08-2020.04.07. The CURB 65, APACH2, SOFA, and PSI score were significantly higher in Critical group than in Severe group. Univariate regression analysis showed that oxygen flow, PO2/FiO2, SOFA and hs-cTnI were closely related to short-term outcome. The corresponding ROC of hs-cTnI, oxygen flow and SOFA for patient death prediction were 0.949, 0.906 and 0.652. hs-cTnI at 47.8 ng/liter predicted death, sensitivity 92.8%, specificity 92.9%; Oxygen flow at 5.5 liter/minute predicted death sensitivity 100%, specificity 77.9%; SOFA score at 5 predicted death sensitivity 100%, specificity 73.8%. Conclusion: Our cohort study demonstrated that inhaled oxygen flow, SOFA score, and myocardial injury at admission in critically ill COVID-19 patients were important indicators for predicting short-term death of patients, the hs-cTnI can be as a risk stratification, which provide a simple method for the to patients and reasonable treatment in time.

Hypothermia preconditioning (HPC) improves cardiac function after cardiac arrest, yet the mechanism is unclear. We hypothesized that HPC-activated adenosine monophosphate-activated protein kinase (AMPK) activity may be involved. Adult male Wistar rats were randomly divided into normothermia Control, HPC (cooling to 32–34°C for 30 min), and HPC + Compound C (Compound C 10 mg/kg was injected intraperitoneally 30 min before HPC group). The rats underwent 7 min of untreated ventricular fibrillation (VF) followed by cardiopulmonary resuscitation (CPR). Cardiac function and hemodynamic parameters were evaluated at 4 h after return of spontaneous circulation (ROSC). Survival status was determined 72 h after ROSC. Mechanistically, we further examined the AMPK-Unc-51 Like Autophagy Activating Kinase 1 (ULK1)-mitophagy pathway and autophagic flux in vivo and in vitro. Six of twelve rats in the Control group, 10 of 12 rats in the HPC group, and 7 of 12 rats in HPC + Compound C group were successfully resuscitated. The 72-h survival rates were 1 of 12 Control, 6 of 12 HPC, and 2 of 12 HPC + Compound C rats, respectively ( P = 0.043). Rats in the HPC group demonstrated greater cardiac contractility and hemodynamic stability which were compromised by Compound C. Furthermore, HPC increased the protein levels of p-AMPKα and p-ULK1 and promoted the expression of mitochondrial autophagy-related genes. Compound C decreased the expression of mitochondrial autophagy-related genes and reduced autophagic flux. Consistent with the observations obtained in vivo, in vitro experiments in cultured neonatal rat cardiomyocytes (CMs) demonstrated that HPC attenuated simulated ischemia–reperfusion-induced CM death, accompanied by increased AMPK-ULK1-mitophagy pathway activity. These findings suggest that AMPK-ULK1-mitophagy pathway was activated by HPC and has a crucial role in cardioprotection during cardiac arrest. Manipulation of mitophagy by hypothermia may merit further investigation as a novel strategy to prevent cardiac ischemia–reperfusion injury.

Objective Cardiac arrest (CA) is caused by a nonshockable rhythm with a low success rate of return of spontaneous circulation (ROSC) and a poor prognosis. This study intended to establish a nonshockable rhythm CA model caused by asphyxia. Materials and methods Healthy adult male Wistar rats were injected with vecuronium bromide to induce CA. After the CA duration reached the target time point, cardiopulmonary resuscitation was performed. The survival status and neurological and cardiac function were evaluated after ROSC. Brain histopathology, including hematoxylin staining, Nissl staining and Terminal dUTP nick-end labeling (TUNEL) staining, was performed to evaluate the surviving cells and apoptotic cells. Apoptosis-related proteins after ROSC for 72 h were analyzed by western blot. Results CA was successfully induced in all animals. The time for the three groups of animals to PEA was 320 ± 22 s in the CA-8 group, 322 ± 28 s in the CA-12 group and 320 ± 18 s in the CA-15 group. The time to asystole was 436 ± 54 s in the CA-8 group, 438 ± 62 s in the CA-12 group and 433 ± 56 s in the CA-15 group. The NDS of rats in the CA group was significantly decreased after ROSC for 24 h. The NDS in the CA-15 group was 5–16 points, while it was 58–67 points and 15–43 points in the CA-8 and CA-12 groups, respectively. The cardiac function of animals in the CA group was impaired after ROSC, and the ejection fraction, fractional shortening, stroke volume and cardiac output, were all significantly decreased. Brain histopathology showed that the number of surviving neurons was decreased, and the number of apoptotic cells was increased in CA group, the longer the CA duration, the more apoptotic cells increased. The expression of the proapoptotic protein Bax and the apoptotic executive protein caspase3 in the hippocampus of CA rats was significantly increased, while the expression of the antiapoptotic protein Bcl-2 was significantly reduced. Conclusions The use of vecuronium can successfully induce CA caused by nonshockable rhythm in rats, which will help to further study the pathophysiological changes after CA by nonshockable rhythm.

Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.

Background and Objective: The role of percutaneous coronary intervention (PCI) after return of spontaneous circulation (ROSC) in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) is controversial. This study aimed to evaluate the effects of PCI on the in-hospital mortality after ROSC in patients with AMI complicated by CA. Methods: The clinical data of 66 consecutive patients with ROSC after CA caused by AMI from January 2006 to December 2015 at the First Affiliated Hospital of Sun Yat-sen University were collected. Among these patients, 21 underwent urgent PCI. We analyzed the clinical characteristics of the patients during hospitalization. Results: The patients who underwent PCI had a higher rate of ST-segment elevation, and their initial recorded heart rhythms were more likely to have a shockable rhythm. Further, they had a high PCI success rate of 100%. The in-hospital mortality in the patients who did not undergo PCI was significantly higher than that in the patients who underwent PCI (68.9% vs 9.5%, P<0.05). Multivariate logistic regression analysis showed that cardiogenic shock (odds ratio [OR], 3.537; 95% CI, 1.047-11.945; P=0.042) and Glasgow Coma Scale score of <= 8 after ROSC (OR, 14.992; 95% CI, 2.815-79.843; P=0.002) were the independent risk factors for in-hospital mortality among the patients. Meanwhile, PCI was a protective factor against in-hospital mortality (OR, 0.063; 95% CI, 0.012-0.318; P=0.001). After propensity matching analysis, the results still showed that PCI (OR, 0.226; 95% CI, 0.028-1.814; P=0.0162) was a protective factor for in-hospital death. Conclusion: The patients with ROSC after CA caused by AMI who underwent PCI had a lower in-hospital mortality than those who did not undergo PCI.

目的:观察外源性导入转录因子EB(TFEB)对缺血性脑卒中小鼠神经功能损伤的影响.方法:(1)15只10周龄雄性C57BL/6小鼠用于建立永久性大脑中动脉阻塞(pMCAO)模型,随机分为假手术组、梗阻2 h组、梗阻4 h组、梗阻8 h组和梗阻24 h组,每组3只,Western blot法检测pMCAO后皮层神经元TFEB、溶酶体相关膜蛋白1(LAMP-1)、微管相关蛋白1轻链3B(LC3B)和cleaved caspase-3蛋白的表达;(2)45只8周龄雄性C57BL/6小鼠分为假手术组、TFEB过表达组、过表达对照组、TFEB敲减组和敲减对照组,每组9只.除假手术组外,其余4组小鼠均经侧脑室注射9型腺相关病毒(AAV9),分别为AAV9-TFEB、AAV9-NC、AAV9-shTFEB和AAV9-shNC,注射2周后建立pMCAO模型,24 h后采用Longa评分法评估小鼠神经功能,磁共振法检测并计算脑梗死体积,TUNEL染色检测皮层神经元细胞凋亡情况,尼氏染色观察皮层神经元细胞形态及数量,Western blot法检测皮层神经元TFEB、LAMP-1、LC3B、cleaved caspase-3蛋白的表达.结果:与假手术组相比,pMCAO后2～24 h,皮层神经元TFEB、LAMP-1及LC3B-II蛋白表达水平均显著下降,而cleaved caspase-3表达升高(P<0.05).侧脑室注射AAV9-TFEB可改善pMACO后小鼠Longa评分,而注射AAV9-shTFEB则恶化Longa评分(P<0.05).磁共振结果显示侧脑室注射AAV9-TFEB可减少脑梗死体积,而注射AAV9-shTFEB则增加脑梗死体积(P<0.05).尼氏染色显示AAV9-TFEB组小鼠皮层神经元细胞数量显著多于AAV9-NC组,AAV9-shTFEB组小鼠皮层神经元细胞数量则显著少于AAV9-shNC组(P<0.05).Western blot结果显示过表达TFEB可增加皮层脑组织LAMP-1和LC3B-II表达,降低cleaved caspase-3表达(P<0.05);敲减TFEB则降低皮层脑组织LAMP-1和LC3B-II表达,增加cleaved caspase-3表达(P<0.05).结论:利用AAV9外源性导入TFEB可通过激活自噬及溶酶体功能而减少pMCAO后皮层神经元细胞凋亡,改善小鼠神经功能.

Objective: To observe hemodynamic characteristics in a series of patients with myocardial injury caused by severe COVID-19-related pneumonia. Materials and Methods: We continuously collected clinical data from severe COVID-19-related pneumonia patients from the West Campus of Union Hospital in Wuhan and Dongguan People's Hospital in Dongguan to explore the prevalence of myocardial injury and hemodynamic characteristics after circulatory failure. Doppler ultrasound and PiCCO2 were used to evaluate the hemodynamics of each patient, and arterial blood gas analysis was performed at the same time. Pearson correlation analysis was used to clarify the relationship between the parameters. Results: A total of 376 patients were observed during the study period. Eighty-seven patients had myocardial injury after admission, and the mean time of myocardial injury after admission was 6 (2, 30) days, from which 16 patients developed hemodynamic instability and 15 died of cardiogenic shock or combined with MODS. Cardiac echocardiography found that the LVEF of all patients was in the normal range and that diastolic function was slightly to moderately impaired. The PiCCO2 data showed that the GEF was significantly decreased in all patients. The dpmx was in normal range. EVLWI, SVRI and GEDI were significantly increased in most patients. Pearson correlation analysis showed that cTNI was significantly related to BNP at hemodynamic instability (r = 0.662, p = 0.005); GEF was related to EVLWI (r = -0.572, p = 0.021) and LAC (r = 0.692, p = 0.003); and EVLWI was affected by LVEF (r = -0.564, p = 0.023), LVDF (r = -0.734, p = 0.001) and PVPI (r = -0.524, p = 0.037). Conclusion: Hemodynamic status after myocardial injury and cardiogenic shock caused by severe COVID-19-related pneumonia was characterized by cardiac preload and increased EVLWI, accompanied by a decline in GEF.

目的:观察改良早期预警评分(MEWS)能否预测上消化道大出血患者的短期预后.方法:收集2018年01月01至2021年01月01日在中山大学附属第一医院急诊科就诊的诊断符合上消化道大出血患者的临床资料;记录患者分诊时的血压、呼吸、体温、脉搏、意识、血氧饱和度,并进行MEWS评分,进行危险分层,分为低危组(MEWS行5)和高危组(MEWS>5).观察患者入院时基本生化检查结果、输注浓缩红细胞数量(RBC)、完成急诊胃镜时间、住院时长和出院时存活状态等指标.结果:共收集到192例患者的临床资料,其中男性136例,女性56例,平均年龄(61±18)岁;胃镜完成时间23(2,72)小时.MEWS评分低危组166例,高危组26例.MEWS评分患者院内死亡率低危组为5/166(3.01％),高危组为8/26(30.76％),两组之间差异显著,而Blatchford评分低危组和高危组院内死亡率分别为6/53(11.32％)和7/139(5.04％),两组之间没有统计学差异.ROC曲线下面积分析显示MEWS评分上消化道大出血患者院内死亡有较好的预测作用,曲线下面积为0.757(P<0.05).结论:MEWS评分对急性高危上消化道大出血患者具有良好的区分度,并且对患者院内死亡具有预测价值,值得临床推广应用.