Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway.

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.

Identification of Potential Biomarkers of Septic Shock Based on Pathway and Transcriptome Analyses of Immune-Related Genes.

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.

Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.

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.

Establishment of a nonshockable rhythm cardiac arrest model caused by asphyxia.

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.

A Facile Strategy to Prepare an Enzyme-Responsive Mussel Mimetic Coating for Drug Delivery Based on Mesoporous Silica Nanoparticles.

Surface functional mesoporous silica nanoparticles (MSNs) have been widely used as promosing materials for drug delivery. Herein, we reported a facile strategy to construct MSNs coated by enzyme-resposive polylysine-dopamine (PLDA) films through self-polymerization of dopamine derivative lysine-dopamine, in which the drug could be loaded and delivered efficiently. In detail, RhB or DOX was used as a drug model and loaded in functional MSNs via a one-pot procedure among MSNs, drug, and lysine-dopamine (LDA) under basic conditions. Owing to the fact that the peptide bonds between lysine and dopamine can be cleaved under triggering by pepsin, the resulting RhB/DOX@PLDA-MSNs exibit enzyme-responsive characterization. After the DOX@PLDA-MSNs enter into the cancer cells, the drug can be released effectively through degradation of peptide bonds under the influence of enzyme in cancer cells, which shows marked anticancer activity in vitro. This facile strategy may provide a new platform to construct enzyme-responsive controlled drug delivery systems.

Activation of autophagy improved the neurologic outcome after cardiopulmonary resuscitation in rats.

OBJECTIVE: Recent studies have shown the existence of autophagy in cerebral ischemia; however, there has been no research on the role of autophagy in cerebral injury after cardiopulmonary resuscitation (CPR). This study was conducted to determine the role of autophagy in an animal model of ventricular fibrillation (VF)/CPR. METHODS: Experiment 1: A total of 48 adult Wistar rats were untreated for 7 minutes after induction of VF using an external transthoracic alternating current, and subsequent CPR was performed to observe the existence of autophagy after the return of spontaneous circulation (ROSC). Experiment 2: A total of 72 rats were pretreated with intracerebroventricular injection of physiologic saline (control group), the autophagy inducer (rapamycin group), or the autophagy inhibitor 3-methyladenine (3-methyladenine group) before ROSC to evaluate the contribution of autophagy to neuronal injury after ROSC. RESULTS: The activation of autophagy was attenuated 2 to 4 hours after ROSC, which was related to the activity decrease of 5'-adenosine monophosphate-activated protein kinase after ROSC. Rapamycin treatment significantly increased the expressions of LC3-II and Beclin-1 after ROSC, attenuated the activation of caspase-3, promoted neuronal survival and decreased neuronal apoptosis, and improved the neurologic deficit score after CPR. CONCLUSIONS: The activation of autophagy after ROSC offered a remarkable tolerance to VF/CPR ischemic insult and improved the neurologic outcomes.

Prearrest hypothermia improved defibrillation and cardiac function in a rabbit ventricular fibrillation model.

BACKGROUND: Hypothermia when cardiopulmonary resuscitation begins may help achieve defibrillation and return of spontaneous circulation (ROSC), but few data are available. OBJECTIVE: The objective of this study was to determine whether prearrest hypothermia improved defibrillation and cardiac function in a rabbit ventricular fibrillation (VF) model. RESULTS: Thirty-six New Zealand rabbits were randomized equally to receive normothermia (Norm) (~39°C), post-ROSC hypothermia (~33°C), or prearrest hypothermia (~33°C). Ventricular fibrillation was induced by alternating current. After 4 minutes of VF, rabbits were defibrillated and given cardiopulmonary resuscitation until ROSC or no response (≥30 minutes). Hemodynamics and electrocardiogram were monitored; N-terminal pro-brain natriuretic peptideand troponin I were determined by enzyme-linked immunosorbent assay. Myocardial histology and echocardiographic data were evaluated. First-shock achievement of perfusion rhythm was more frequent in prearrest than normothermic animals (7/12 vs 1/12; P=.027). After ROSC, dp/dtmax was higher in prearrest than normothermic animals (P<.001). Left ventricular end-systolic pressure was higher in prearrest than normothermic animals (P=.001). At 240 minutes after ROSC, troponin I and N-terminal pro-brain natriuretic peptide were lower in prearrest than normothermic animals (15.74±2.26 vs 25.09±1.85 ng/mL and 426±23 vs 284±45 pg/mL, respectively), the left ventricular ejection fraction and cardiac output were lower in the Norm group than other 2 groups (P<.01). Myocardial histology was more disturbed in normothermic than post-ROSC and prearrest animals, but was not different in the latter 2 groups. CONCLUSIONS: Induction of hypothermia before VF led to improved cardiac function in a rabbit VF model through improving achievement of perfusing rhythm by first-shock defibrillation and facilitating resuscitation.

Assessing the early changes of cerebral glucose metabolism via dynamic (18)FDG-PET/CT during cardiac arrest.

To study the changes of cerebral glucose metabolism (CGM) during the phase of return of spontaneous circulation (ROSC) after cardiac arrest (CA), we used 18-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)FDG-PET/CT) to measure the CGM changes in six beagle canine models. After the baseline (18)FDG-PET/CT was recorded, ventricular fibrillation (VF) was induced for 6 min, followed by close-chest cardiopulmonary resuscitation (CPR) in conjunction with intravenous (IV) administration of epinephrine and external defibrillator shocks until ROSC was achieved, within 30 min. The (18)FDG was recorded prior to intravenous administration at 0 h (baseline), and at 4, 24, and 48 h after CA with ROSC. We evaluated the expression of two key control factors in canine CGM, hexokinase I (HXK I) and HXK II, by immunohistochemistry at the four above mentioned time points. Electrically induced VF of 6 min duration was successfully induced in the dogs. Resuscitation was then performed to maintain blood pressure stability. Serial (18)FDG-PET/CT scans found that the CGM decreased at 4 h after ROSC and remained lower than the baseline even at 48 h. The expression of HXK I and II levels were consistent with the changes in CGM. These data from our present work showed that (18)FDG-PET/CT imaging can be used to detect decreased CGM during CA and was consistent with the results of CMRgl. Furthermore, there were also concomitant changes in the expression of HXK I and HXK II. The decrease in CGM may be an early sign of hyperacute global cerebral ischemia.

A new species of Neobelocera Ding & Yang (Hemiptera: Delphacidae: Delphacinae: Tropidocephalini) from China, with a key to species of the genus.

Neobelocera medogensis sp. nov. (Hemiptera: Delphacidae: Delphacinae: Tropidocephalini) is described and illustrated from Mȇdog, Tibet, China. The new species can be easily separated from other known species in the genus Neobelocera by the color of tegmina and the form of the male genitalia. A key for separation of all known species of Neobelocera is also provided.

Early enhanced external counter pulsation improves neurological recovery after the return of spontaneous circulation in a mongrel dog cardiac arrest model*.

OBJECTIVES: The aim of this study was to investigate whether early enhanced external counter pulsation therapy after cardiopulmonary resuscitation improved neurological outcome in a mongrel dog cardiac arrest model. DESIGN: Randomized, animal study. SETTING: Assisted circulation laboratory. SUBJECTS: Twenty-four healthy male adult dogs (12-14 kg). INTERVENTIONS: After minutes of untreated ventricular fibrillation followed by 2 minutes of cardiopulmonary resuscitation, the dogs were randomized to receive 4 hours of enhanced external counter pulsation therapy, to receive 4 hours of hypertension with over 140 mm Hg or to be a control. MEASUREMENTS: Blood pressure and left ventricular ejection fraction were recorded. Cerebral flow was assessed using magnetic resonance imaging. Arterial blood gases and endothelium-derived vasoactive substances were assessed before cardiac arrest and 4 hours after the return of spontaneous circulation. Neurological outcome was assessed by the neurologic deficit score and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. RESULTS: Enhanced external counter pulsation significantly improved the left ventricular ejection fraction and increased common carotid artery blood flow and shear stress. Enhanced external counter pulsation increased both relative cerebral blood volume (RCBV, p = 0.043) and relative cerebral blood flow (RCBF, p = 0.012) in animals 4 hours after return of spontaneous circulation. Enhanced external counter pulsation therapy promoted the production of nitric oxide and tissue plasminogen activator and decreased the release of endothelin-1 (p = 0.013) after return of spontaneous circulation. Treatment with norepinephrine in the high mean artery pressure also increased common carotid artery blood flow and shear stress. However, no effects on the left ventricular ejection fraction, the production of nitric oxide and tissue plasminogen activator, or the release of endothelin-1 were found. The neurologic deficit scores of the animals were significantly lower at 24, 48, 72, and 96 hours in the enhanced external counter pulsation group, as well as at 24, 72, and 96 hours compared with animals in the control group after return of spontaneous circulation. Fewer apoptotic neurons were observed in the animals in the enhanced external counter pulsation group compared with the animals in the control and hypertension groups. CONCLUSIONS: These data indicated that the treatment of early enhanced external counter pulsation improved neurological outcome by both increasing cerebral blood flow and improving the recovery of microcirculation after return of spontaneous circulation. The treatment of early enhanced external counter pulsation can be a good option for protecting the brain after return of spontaneous circulation.

The effect of an NgR1 antagonist on the neuroprotection of cortical axons after cortical infarction in rats.

We investigated the effect of the soluble Nogo66 receptor (sNgR-Fc) on the protection of cortical axons after cortical infarction in rats. The cortical infarction was induced by photothrombotic cortical injury (PCI) in Sprague-Dawley rats, after which sNgR-Fc was injected into the lateral ventricle. The ipsilesional cortices were harvested for analyses using histochemical and transmission-electron microscope techniques. The involved signaling pathways, which include RhoA, JNK, c-JUN and ATF-2, were detected by Western blot. Serious pathologies were found in the brains of the rats after injury, including edemas in the axoplasms of axons that have no medulla sheath and a thickening or shrinkage in the sheath of the axons that have medulla sheathes. However, these pathologies improved after sNgR-Fc treatment. The levels of GTP-RhoA, p-JNK, p-c-JUN and p-ATF-2 in the PCI group were increased when compared with their levels in the sham-operation group (P < 0.05), and animals receiving the sNgR-Fc treatment showed lower expression levels of these proteins when compared with the sham-operation group (P < 0.05). Our results suggest that sNgR-Fc can alleviate the pathological changes of axons following cortical infarction via decreasing the activation of RhoA/JNK signaling pathways.

A comparison of bilevel and continuous positive airway pressure noninvasive ventilation in acute cardiogenic pulmonary edema.

BACKGROUND: Whether bilevel positive airway pressure (BiPAP) is advantageous compared with continuous positive airway pressure (CPAP) in acute cardiogenic pulmonary edema (ACPO) remains uncertain. The aim of the meta-analysis was to assess potential beneficial and adverse effects of CPAP compared with BiPAP in patients with ACPO. METHODS: Randomized controlled trials comparing the treatment effects of BiPAP with CPAP were identified from electronic databases and reference lists from January 1966 to December 2012. Two reviewers independently assessed study quality. In trials that fulfilled inclusion criteria, we critically evaluate the evidence for the use of noninvasive ventilation on rates of hospital mortality, endotracheal intubation, myocardial infarction, and the length of hospital stay. Data were combined using Review Manager 4.3 (The Cochrane Collaboration, Oxford, UK). Both pooled effects and 95% confidence intervals (CIs) were calculated. RESULTS: Twelve randomized controlled trials with a total of 1433 patients with ACPO were included. The hospital mortality (relative risk [RR], 0.86; 95% CI, 0.65-1.14; P = .46; I(2) = 0%) and need for requiring invasive ventilation (RR, 0.89; 95% CI, 0.57-1.38; P = .64; I(2) = 0%) were not significantly different between patients treated with CPAP and those treated with BiPAP. The occurrence of new cases of myocardial infarction (RR, 0.95; 95% CI, 0.77-1.17; P = .53, I(2) = 0%) and length of hospital stay (RR, 1.01; 95% CI, -0.40 to 2.41; P = .98; I(2) = 0%) were also not significantly different between the 2 groups. CONCLUSIONS: There are no significant differences in clinical outcomes when comparing CPAP vs BiPAP. Based on the limited data available, our results suggest that there are no significant differences in clinical outcomes when comparing CPAP with BiPAP.

Enhanced external counterpulsation improves cerebral blood flow following cardiopulmonary resuscitation.

BACKGROUND: To investigate the therapeutic value of enhanced external counterpulsation (EECP) on recovery of cerebral blood flow following cardiac arrest (CA) and successful resumption of spontaneous circulation (ROSC) by cardiopulmonary resuscitation. METHODS: CA models were conducted using beagle dogs induced by alternating current. After successful ROSC by cardiopulmonary resuscitation, 16 dogs were randomly divided into the EECP and control group (n = 8 per group). Dogs underwent dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging at baseline prior to CA and during the 3 days following ROSC. Mean blood pressure, right common carotid artery blood flow, intracranial microcirculation and blood lactate levels were measured. Neurological outcome was assessed by the neurologic deficit score. Hematoxylin-eosin staining and transmission electron microscopy were performed for morphology and microconstruction of the cerebral cortex. RESULTS: The EECP group exhibited a significant elevation in right common carotid artery blood flow, intracranial microcirculation and a substantial decrease in blood lactate levels relative to the control group. Relative cerebral blood flow and volume were higher in the EECP group during the 3 days. Apparent diffusion coefficients were significantly higher in the EECP group on the first and third days. After ROSC, the neurologic deficit score was significantly higher in the control group compared to those in the EECP group during the three days of experiment. The cell swelling of neurons and increase of mitochondrial mass were more pronounced in the control group. CONCLUSION: EECP is beneficial for recovery of cerebral blood flow and attenuation of ischemic cerebral edema following CA and successful ROSC.

Revision of the subgenus Cosmiomorpha (Cosmiomorpha)(Coleoptera: Scarabaeidae: Cetoniinae).

A taxonomic revision of the subgenus Cosmiomorpha (Cosmiomorpha) Saunders is presented. Seven species are recognized, including four described herein, C. fortis new species, C. nigripedis new species, C. maolanensis new species, and C. cheni new species all from China. Cosmiomorpha baryi Bourgoin and C. squamulosa Schürhoff are placed as junior synonyms of C. decliva Janson, and C. angulosa Fairmaire as a synonym of C. decliva is also confirmed. Lectotypes are designated for C. decliva Janson, C. angulosa Fairmaire, and C. squamulosa Schürhoff. Color photographs and diagnoses of all species are provided, with comments on intraspecific variations. A key to males is also presented. Localities of "Siào-Lòu" and "Se Pin-Lou Chan" are discussed with a map. 

Transcription factor EB (TFEB) improves ventricular remodeling after myocardial infarction by inhibiting Wnt/ß-catenin signaling pathway.

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 ß-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 ß-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/ß-catenin signaling pathway.

Tandem mass tag-based proteomics analysis of protein changes in the freezing and thawing cycles of Trachurus murphyi.

We investigated the proteome variations in Trachurus murphyi with different cycles of freezing and thawing (FT) under frozen storage. A total of 2,482 proteins were assessed quantitatively, of which 269 proteins were recognized as differential abundance proteins during the second FT cycle until the eighth FT cycle. Bioinformatics analysis on gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses of Differential Analysis of Proteins (DAPs) indicated multiple DAPs engaged with the protein structure, metabolic enzymes, and protein turnover. In addition, some of the observed proteins were probably the underlying markers of protein oxidation (PO). The analysis of PO sites revealed the sites of PO, such as amino adipic semialdehydes, γ-glutamic semialdehydes, and Schiff bases. Bioinformatics analyses demonstrated the involvement of differentially expressed proteins in the Hippo signaling pathway (Ko04390), indicating strong protein degradation with greater numbers of FT cycles under frozen storage. It provides an insight into quality stability from a proteomics quality perspective at the molecular level. The results obtained have deepened our current understandings of the mechanisms that reveal variations in proteomes and quality, as well as help promote quality control of T. murphyi across the cold transportation chain. PRACTICAL APPLICATION: Temperature fluctuation is one of the core issues during frozen food storage and distribution faced by the frozen food industry. Fluctuation may result in microstructural changes, ice recrystallization, and protein change in frozen food products. Tandem mass tag-based methods were adopted to study proteome variations in Trachurus murphyi muscles under different cycles of freezing and thawing under frozen storage conditions in this paper. The results obtained have deepened our current understandings of the mechanisms that reveal variations in proteomes and quality, as well as help promote quality control of T. murphyi across the cold transportation chain.

High-Sensitivity Troponin I is an Indicator of Poor Prognosis in Patients with Severe COVID-19 Related Pneumonia.

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 may provide a simple method for the physicians to identify high-risk patients and give reasonable treatment in time.

Hypothermia preconditioning improves cardiac contractility after cardiopulmonary resuscitation through AMPK-activated mitophagy.

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.

Identification and Validation of Novel Potential Pathogenesis and Biomarkers to Predict the Neurological Outcome after Cardiac Arrest.

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.

Cloning and characterization of piggyBac-like elements in lepidopteran insects.

PiggyBac-like elements (PLE) are widespread in variety of organisms, however, few of them are active or have an intact transposon structure. To further define the distribution PLEs in Lepidoptera, where the original active piggyBac IFP2 was discovered, and potentially isolate new functional elements, a survey for PLEs by PCR amplification and Southern dot blots was performed. Two new PLEs, AyPLE and AaPLE, were successfully isolated from the noctuid species, Agrotis ypsilon and Argyrogramma agnate, respectively. These elements were found to be closely related to each other by sequence similarity, and by sharing the same 16 bp inverted terminal repeat sequences. The AyPLE1.1 and AaPLE1.1 elements are structurally intact having characteristic TTAA target site duplications, inverted terminal repeats and intact open reading frames encoding putative transposases with the presumed piggyBac DDD domains, which are features consistent with autonomous functional transposons. Phylogenetic analysis revealed that AyPLE1.1 and AaPLE1.1 cluster with another noctuid species element, HaPLE1.1, suggesting a common ancestor for the three types of PLEs. This contributes to our understanding of the distribution and evolution of piggyBac in Lepidoptera.