CREB activity maintains the survival of cingulate cortical pyramidal neurons in the adult mouse brain

Cyclic AMP-responsive element binding protein (CREB) activity is known to contribute to important neuronal functions, such as synaptic plasticity, learning and memory. Using a microelectroporation technique to overexpress dominant negative mutant CREB (mCREB) in the adult mouse brain, we found that overexpression of mCREB in the forebrain cortex induced neuronal degeneration. Our findings suggest that constitutively active CREB phosphorylation is important for the survival of mammalian cells in the brain

Incidence, risk factors and prognostic effect of imaging right ventricular involvement in patients with COVID-19: a dose–response analysis protocol for systematic review

Introduction Emerging evidence has shown that COVID-19 infection may result in right ventricular (RV) disturbance and be associated with adverse clinical outcomes. The aim of this meta-analysis is to summarise the incidence, risk factors and the prognostic effect of imaging RV involvement in adult patients with COVID-19.Methods A systematical search will be performed in PubMed, EMBase, ISI Knowledge via Web of Science and preprint databases (MedRxiv and BioRxiv) (until October 2021) to identify all cohort studies in adult patients with COVID-19. The primary outcome will be the incidence of RV involvement (dysfunction and/or dilation) assessed by echocardiography, CT or MRI. Secondary outcomes will include the risk factors for RV involvement and their association with all-cause mortality during hospitalisation. Additional outcomes will include the RV global or free wall longitudinal strain (RV-GLS or RV-FWLS), tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and RV diameter. Univariable or multivariable meta-regression and subgroup analyses will be performed for the study design and patient characteristics (especially acute or chronic pulmonary embolism and pulmonary hypertension). Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of RV involvement incidence and related risk factors, association with all-cause mortality, and other RV parameters (RV-GLS or RV-FWLS, TAPSE, S’, FAC and RV diameter). Both linear and cubic spline regression models will be used to explore the dose–response relationship between different categories (>2) of RV involvement and the risk of mortality (OR or HR).Ethics and dissemination There was no need for ethics approval for the systematic review protocol according to the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital. This meta-analysis will be disseminated through a peer-reviewed journal for publication.PROSPERO registration number CRD42021231689

Role and intervention of PAD4 in NETs in acute respiratory distress syndrome

Abstract Background Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Acute respiratory distress syndrome (ARDS) is a common sepsis-associated injury that can increase postoperative mortality but the mechanism is still unclear. Main text The role of neutrophils in the pathophysiology of sepsis was deeply challenged after the discovery of NETosis, a process resulting in neutrophil extracellular traps (NETs) release. NETs can support thrombin generation and the concept of immunothrombosis has emerged as a new innate response to infection. Immunothrombosis leads to thrombosis in microvessels and supports immune cells together with specific thrombus-related molecules. ARDS is a common sepsis-associated organ injury. Immunothrombosis participates in thrombosis in pulmonary capillaries. Intervention regarding immunothrombosis in ARDS is a key scientific problem. PAD4 is the key enzyme regulating the NET skeleton protein histone H3 to citrulline histone to form NETs in immune thrombosis. This review summarizes NETosis and immunohaemostasis, ARDS and therapeutic opportunities targeting PAD4 via PAD4 inhibitors and lncRNAs potentially, providing future therapies. Conclusions We identified and summarized the fundamental definition of ARDS and the concept of immune thrombosis and its composition. NETs activation has become particularly relevant in the formation of immune thrombosis. The taskforce highlighted the intervention targets of PAD4, including noncoding RNAs, potentially providing future therapeutic targets to confront the high postoperative mortality of ARDS

Which factor is the most effective one in metabolic Sydrome on the outcomes after coronary artery bypass graft surgery? A cohort study of 5 Years

Abstract Background Metabolic Syndrome and diabetes mellitus are risk factors for cardiovascular disease. However, the effects of Metabolic Syndrome with or without diabetes on perioperative and long-term morbidity and mortality after Coronary Artery Bypass Graft remain unclear. Methods An retrospective study was performed on 1166 patients who received isolated primary Coronary Artery Bypass Graft in Fuwai hospital. They were divided into three groups: control, Metabolic Syndrome of three factors together with diabetes and Metabolic Syndrome of three factors without diabetes (n = 868, 76 and 222 respectively). Analysis of variance, Chi-rank test, Fisher’s exact test, Log-rank test, Cox and Logistic regression models were used for data processing. Outcomes were postoperative and 5-year survival and morbidities. Results There were no significant differences between groups in in-hospital postoperative complications, epinephrine use, stroke, atrial fibrillation, renal failure, coma, myocardial infarction and repeated revascularization. Patients in the Metabolic Syndrome with diabetes, Metabolic Syndrome without diabetes and control groups, respectively, showed significant difference in perioperative Major Adverse Cerebral Cardiovascular Events (30.3% vs. 21.2%, 16.7%, P = 0.0071) and mortality (11.8% vs. 2.7%, 3.11%, P = 0.0003). The Metabolic Syndrome with diabetes group had higher rates of perioperative mortality than Metabolic Syndrome without diabetes (P = 0.0017, P of Fisher Test = 0.0039). Compared with non-diabetic patients with Metabolic Syndrome, those with Metabolic Syndrome and diabetes had increased long-term mortality (Adjusted HR: 4.3; 95% CI: 1.4–13.3; P = 0.0113) and Major Adverse Cerebral Cardiovascular Events (Adjusted OR: 1.7; 95% CI: 1.0–2.8; P = 0.048). Control and non-diabetic Metabolic Syndrome groups did not differ in long-term mortality but controls had lower rates of Major Adverse Cerebral Cardiovascular Events (Adjusted OR: 0.79; 95% CI: 0.64–0.98; P = 0.0329). Conclusions There were significance differences between the three groups in perioperative Major Adverse Cerebral Cardiovascular Events and mortality after Coronary Artery Bypass Graft. Compared with non-diabetic Metabolic Syndrome patients, patients with Metabolic Syndrome and diabetes had higher long-term Major Adverse Cerebral Cardiovascular Events and mortality. While patients free of MetS and diabetes were associated with lower incidence of long-term Major Adverse Cerebral Cardiovascular Events after Coronary Artery Bypass Graft

Spinal cord organogenesis model reveals role of Flk1+ cells in self-organization of neural progenitor cells into complex spinal cord tissue

A platform for studying spinal cord organogenesis in vivo where embryonic stem cell (ESC)-derived neural progenitor cells (NPC) self-organize into spinal cord-like tissue after transplantation in subarachnoid space of the spinal cord has been described. We advance the applicability of this platform by imaging in vivo the formed graft through T2w magnetic resonance imaging (MRI). Furthermore, we used diffusion tensor imaging (DTI) to verify the stereotypical organization of the graft showing that it mimics the host spinal cord. Within the graft white matter (WM) we identified astrocytes that form glial limitans, myelinating oligodendrocytes, and myelinated axons with paranodes. Within the graft grey matter (GM) we identified cholinergic, glutamatergic, serotonergic and dopaminergic neurons. Furthermore, we demonstrate the presence of ESC-derived complex vasculature that includes the presence of blood brain barrier. In addition to the formation of mature spinal cord tissue, we describe factors that drive this process. Specifically, we identify Flk1+ cells as necessary for spinal cord formation, and synaptic connectivity with the host spinal cord and formation of host-graft chimeric vasculature as contributing factors. This model can be used to study spinal cord organogenesis, and as an in vivo drug discovery platform for screening potential therapeutic compounds and their toxicity. Keywords: Embryonic stem cells, Neural progenitor cells, Spinal cord organogenesis, Flk

Use of Pulmonary Artery Catheter in Coronary Artery Bypass Graft. Costs and Long-Term Outcomes

<div><p>Background</p><p>Pulmonary artery catheters (PAC) are used widely to monitor hemodynamics in patients undergoing coronary bypass graft (CABG) surgery. However, recent studies have raised concerns regarding both the effectiveness and safety of PAC. Therefore, our aim was to determine the effects of the use of PAC on the short- and long-term health and economic outcomes of patients undergoing CABG.</p><p>Methods</p><p>1361 Chinese patients who consecutively underwent isolated, primary CABG at the Cardiovascular Institute of Fuwai Hospital from June 1, 2012 to December 31, 2012 were included in this study. Of all the patients, 453 received PAC during operation (PAC group) and 908 received no PAC therapy (control group). Short-term and long-term mortality and major complications were analyzed with multivariate regression analysis and propensity score matched-pair analysis was used to yield two well-matched groups for further comparison.</p><p>Results</p><p>The patients who were managed with PAC more often received intraoperative vasoactive drugs dopamine (70.9% vs. 45.5%; P<0.001) and epinephrine (7.7% vs. 2.6%; P<0.001). In addition, costs for initial hospitalization were higher for PAC patients ($14,535 vs.$13,873, respectively, p = 0.004). PAC use was neither associated with the perioperative mortality or major complications, nor was it associated with long-term mortality and major adverse cardiac and cerebrovascular events. In addition, comparison between two well-matched groups showed no significant differences either in baseline characteristics or in short-term and long-term outcomes.</p><p>Conclusions</p><p>There is no clear indication of any benefit or harm in managing CABG patients with PAC. However, use of PAC in CABG is more expensive. That is, PAC use increased costs without benefit and thus appears unjustified for routine use in CABG surgery.</p></div

Long-Term Outcomes according to PAC status.

<p>A. Survival rate B. Freedom from myocardial infarction (MI) C. Freedom from cerebrovascular accident (CVA) D. Freedom from renal failure.</p