PRKCA Promotes Mitophagy through the miR-15a-5p/PDK4 Axis to Relieve Sepsis-Induced Acute Lung Injury.

Acute lung injury (ALI) caused by sepsis is a common respiratory critical illness with high morbidity and mortality. Protein kinase C-alpha (PRKCA) plays a protective role in sepsis-induced ALI. However, the detailed molecular mechanism of PRKCA in ALI caused by sepsis is unclear. Animal and cell models of sepsis were established by cecal ligation and puncture (CLP)-surgery and lipopolysaccharide (LPS)/interferon-gamma (IFN-γ) treatment, respectively. Lentivirus transfection was used to overexpress PRKCA. H&E staining and lung injury in CLP-surgery mice were evaluated. Gene expression was evaluated using qPCR and Western blotting. The expression of TNF-α, IL-1ß, and IL-6 was examined using qPCR and ELISA. The expression of LC3 and TOM20 was evaluated using immunofluorescence assays. Cell apoptosis was assessed using a flow cytometry assay. The bond between miR-15a-5p and PDK4 was confirmed by dual-luciferase reporter gene and RNA immunoprecipitation assays. In vivo and in vitro, PRKCA overexpression reduced lung injury to prompt mitophagy and inhibit the inflammatory response, ROS production, and cell apoptosis. miR-15a-5p was highly expressed in macrophages treated with LPS/IFN-γ and was negatively mediated by PRKCA. The overexpression of miR-15a-5p reduced the effects of PRKCA upregulation in macrophages. miR-15a-5p could restrain mitophagy in LPS/IFN-γ-treated macrophages by directly targeting PDK4. Furthermore, PDK4 knockdown reversed the inhibition of cell apoptosis and inflammatory factor release caused by miR-15a-5p silencing. The PRKCA/miR-15a-5p/PDK4 axis alleviated ALI caused by sepsis by promoting mitophagy and repressing anti-inflammatory response.

Early clinical predictors for the prognosis of invasive pneumococcal disease.

BACKGROUND: Risk factors related to mortality due to invasive pneumococcal disease (IPD) have been unveiled previously, but early clinical manifestations of IPD based on prognosis remain uncovered. METHODS: The demographic characteristics, clinical features, serotype, antibiotic susceptibility, and outcomes of 97 hospitalized children with laboratory-confirmed IPD from Suzhou, China, were collected and analyzed retrospectively. RESULTS: The median age was 0.69 (0.49-1.55) years in the non-survivor group compared with 2.39 (0.90-3.81) years in the survivor group. The mortality of 97 children with laboratory-confirmed IPD was 17.5% (17/97), and 53.6% of them were aged less than 2 years. Pathogens were mainly from the blood and cerebrospinal fluid, and sepsis was the most frequent type. Statistically significant differences were found in hyperpyrexia, vomiting, anorexia, lethargy, poor perfusion of extremities, Hb level, and Plt count between the nonsurvival and survival groups. Further, the multivariate regression analysis showed that early signs, including hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities, were independent risk factors for the in-hospital mortality of children with laboratory-confirmed IPD. The mortality was also associated with antimicrobial sensitivity in pneumococcal isolates. The microbes in 1/17 (5.9%) children who were prescribed an antibiotic showed antimicrobial sensitivity in the nonsurvival group, compared with 21/80 (26.3%) children who survived. The most common serotypes identified were 6B (35.3%, 6/17), 14 (23.5%, 4/17), 19F (23.5%, 4/17), 19A (5.9%, 1/17), 23F (5.9%, 1/17), and 20 (5.9%, 1/17) in the nonsurvival group. The coverage of IPD serotypes of the 7-valent pneumococcal conjugate vaccine (PCV7) was 88.2% (15/17), while that of the 13-valent S. pneumoniae vaccine (PCV13) was 94.1% (16/17) of the coverage in the nonsurvival group. CONCLUSIONS: Recurrent hyperpyrexia, vomiting, anorexia, lethargy, and poor perfusion of extremities in the early stage were independent predictors for the in-hospital mortality of children with laboratory-confirmed IPD. Appropriate use of antibiotics and PCV immunization were the keys to improve the outcome of IPD.

Withdrawal of treatment in a pediatric intensive care unit at a Children's Hospital in China: a 10-year retrospective study.

BACKGROUND: Published data and practice recommendations on end-of-life care generally reflect Western practice frameworks; there are limited data on withdrawal of treatment for children in China. METHODS: Withdrawal of treatment for children in the pediatric intensive care unit (PICU) of a regional children's hospital in eastern China from 2006 to 2017 was studied retrospectively. Withdrawal of treatment was categorized as medical withdrawal or premature withdrawal. The guardian's self-reported reasons for abandoning the child's treatment were recorded from 2011. RESULTS: The incidence of withdrawal of treatment for children in the PICU decreased significantly; for premature withdrawal the 3-year average of 15.1% in 2006-2008 decreased to 1.9% in 2015-2017 (87.4% reduction). The overall incidence of withdrawal of care reduced over the time period, and withdrawal of therapy by guardians was the main contributor to the overall reduction. The median age of children for whom treatment was withdrawn increased from 14.5 months (interquartile range: 4.0-72.0) in 2006 to 40.5 months (interquartile range: 8.0-99.0) in 2017. Among the reasons given by guardians of children whose treatment was withdrawn in 2011-2017, "illness is too severe" ranked first, accounting for 66.3%, followed by "condition has been improved" (20.9%). Only a few guardians ascribed treatment withdrawal to economic reasons. CONCLUSIONS: The frequency of withdrawal of medical therapy has changed over time in this children's hospital PICU, and parental decision-making has been a large part of the change.