The cross talk between cGMP signal pathway and PKC in pulmonary endothelial cell angiogenesis.

Angiogenic proliferation of vascular endothelial cells is believed to play an important role in pulmonary vascular remodeling in pulmonary arterial hypertension. In the present study, we found that c-GMP (cyclic guanosine monophosphate) inhibited the proliferation and tube formation of pulmonary vascular endothelial cells induced by TGF-ß1, and that this process was reversed by PKG (protein kinase G) inhibitor and PKC (protein kinase C) inhibitor. In addition, small interfering RNA (siRNA) targeting ERK also reduced cellular proliferation. Furthermore, western blotting showed that cGMP down-regulated the phosphorylation level of ERK1/2, which was reversed not only by PKG inhibitor but also by PKC inhibitor. Silencing different PKC isoforms showed that PKCΔ, PKCγ and PKCα were involved in ERK phosphorylation, suggesting that PKC kinases have a permissive action. Three subtypes, PKCΔ, PKCγ and PKCα are likely to be involved the phosphorylation suppression of ERK included cGMP. Taken together, these data suggest that ERK phosphorylation mediates the proliferation of pulmonary vascular endothelial cells, and PKC kinases have a permissive action in this process.

Clinical features of omicron SARS-CoV-2 variants infection associated with co-infection and ICU-acquired infection in ICU patients.

Background: Although the decreasing rate of hospital admission in the omicron wave has led countries to loosen control, still the patients requires ICU admission. It is common for viral respiratory infections to be co-infected with bacteria. However, the difference between co-infection and ICU-acquired infection on their clinical characteristics and outcomes during the Omicron wave was little reported. Methods: Clinical and microbiological data were collected from ICU patients with omicron infection between April 1st, 2022, and May 31th, 2022 and a comprehensive comparative study of the clinical characteristics and endpoint were conducted. Results: The Omicron SARS-CoV-2 variants-infected patients requiring intensive care had high rates of co-infection (42.55%). Additionally, the ICU COVID-19 patients with co-infection showed more severe clinical features compared to those with ICU-acquired infection. Furthermore, Multivariate Cox analysis demonstrated that co-infection (hazard ratio: 4.670, p = 0.018) was a significant risk factor for poor outcomes in ICU patients with COVID-19. Besides, Kaplan-Meier survival curve analysis revealed that COVID-19 patients with co-infection had a significantly shorter 28-Day survival time compared to those with ICU-acquired infection (p < 0.001). Finally, our investigation identified a significant association between the presence of Candida app. in the broncho-alveolar lavage and an elevated risk of mortality (OR: 13.80, p = 0.002) and invasive ventilation (OR: 5.63, p = 0.01). Conclusion: Co-infection is prevalent among patients requiring intensive care and is linked to unfavorable outcomes in the Omicron wave. Consequently, more attention may be needed for the empirical antibacterial treatment in ICU patients within the COVID-19 Omicron variant, especially anti-fungi.

I(h) "run-up" in rat neocortical neurons and transiently rat or human HCN1-expressing HEK293 cells.

Hyperpolarization-activated cyclic nucleotide-gated ion channels (HCN) are key determinants of CNS functions. Here we describe an increase in hyperpolarization-activated current (I(h)) at the beginning of whole-cell recordings in rat layer 5 cortical neurons. For a closer investigation of this I(h) increase, we overexpressed the predominant layer 5 rat subunit HCN1 in HEK293 cells. We characterized the resulting I(h) in the cell-attached and whole-cell configurations. Breaking into whole-cell configuration led to about a 30% enhancement of rat HCN1-mediated I(h) accompanied by a depolarizing shift in voltage dependence and an accelerated time course of activation. This current enhancement is not species specific; for human HCN1, the current similarly increases in amount and kinetics. Although the changes were bound to cytosolic solution exchange, they were independent of cAMP, ATP, GTP, and the phosphate group donor phosphocreatine. Together, these data provide a characterization of heterologous expression of rat HCN1 and suggest that cytosolic contents suppress I(h). Such a mechanism might constitute a reserve in h-channel function in vivo.

Risk Factors for the Postoperative Transfusion of Allogeneic Blood in Orthopedics Patients With Intraoperative Blood Salvage: A Retrospective Cohort Study.

The purpose of this study is to explore the risk factors affecting the postoperative transfusion of allogeneic blood in patients undergoing orthopedics surgery with intraoperative blood salvage (IBS). A retrospective study of 279 patients undergoing orthopedic surgeries with IBS from May 2013 to May 2015 was enrolled. The binary logistic regression was used to find out the risk factors associated with postoperative transfusion of allogeneic blood in orthopedics patients with IBS, and then receiver operating characteristic (ROC) curve was drawn to determine the optimal threshold of the regression model.Single factor analysis showed that age, American Society of Anesthesiologists (ASA) grade, preoperative hemoglobin, operation time, received autologous blood, the laying time of autologous blood, bleeding volume, and postoperative drainage volume had significant effects on postoperative allogeneic blood transfusion.In binary logistic regression analysis, the independent factors predicting orthopedic patients with IBS need to transfuse allogeneic blood after surgeries were age (odds ratio [OR] = 0.415, P = 0.006), ASA grade (OR = 2.393, P = 0.035), preoperative hemoglobin (OR = 0.532, P = 0.022), and postoperative drainage volume (OR = 4.279, P = 0.000). The area under ROC curve was 0.79 and the predicted accuracy rate of the model was 81.58%.After operation, the orthopedic patients with IBS still have a high allogeneic blood transfusion rate, and IBS is not a perfect blood protection method. The logistic regression model of our study provides a reliable prediction for postoperative transfusion of allogeneic blood in orthopedic patients with IBS, which have a certain reference value.