Spliceosomal GTPase Eftud2 regulates microglial activation and polarization

Elongation factor Tu GTP binding domain protein 2(Eftud2)is a spliceosomal GTPase that serves as an innate immune modulator restricting virus infection.Microglia are the resident innate immune cells and the key players of immune response in the central nervous system.However,the role of Eftud2 in microglia has not been reported.In this study,we performed immunofluorescent staining and western blot assay and found that Eftud2 was upregulated in microglia of a 5xFAD transgenic mouse model of Alzheimer’s disease.Next,we generated an inducible microglia-specific Eftud2 conditional knockout mouse line(CX3CR1-CreER;Eftud2^(f/f) cKO)via Cre/loxP recombination and found that Eftud2 deficiency resulted in abnormal proliferation and promoted anti-inflammatory phenotype activation of microglia.Furthermore,we knocked down Eftud2 in BV2 microglia with siRNA specifically targeting Eftud2 and found that Eftud2-mediated regulation of microglial proinflammatory/anti-inflammatory phenotype activation in response to inflammation might be dependent on the NF-κB signaling pathway.Our findings suggest that Eftud2 plays a key role in regulating microglial polarization and homeostasis possibly through the NF-κB signaling pathway.

Applications of mPCR testing reduced initial antibiotic use and duration of mechanical ventilation in virus-infected children with severe community-acquired pneumonia admitted to the PICU

Community-acquired pneumonia(CAP)remains the leading cause of morbidity and mortality among children worldwide.It is critical for these patients to select and timely initiate appropriate empirical antimicrobial therapy against the causative pathogens[1].However,conventional pathogen-detecting methods,such as culture and serology,have no prospect of altering empiric therapy owing to their time delay in obtaining results and to their lower detection rates[2].Recent advances in molecular diagnostic assays,such as multiplex polymerase chain reaction PCR(mPCR)methods,have been used to detect multiple pathogens in CAP simultaneously within two hours and have dramatically improved the ability to diagnose respiratory pathogens[3].However,whether this molecular diagnosis method can reduce the use of antibiotics and can improve prognosis in severe CAP children,especially those less than 5 years old,remains to be explored.

Comparison between hospital- and community-acquired septic shockin children: a single-center retrospective cohort study

Background We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factorsbetween children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatricintensive care unit (PICU).Methods This retrospective study enrolled children with septic shock at the PICU of Beijing Children’s Hospital from January1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided intothe HASS and CASS group. Logistic regression analysis was used to identify risk factors for mortality.Results A total of 298 children were enrolled. Among them, 65.9% (n = 91) of HASS patients had hematologic/oncologicdiseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASSpatients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratoryor central nervous system. The 28-day mortality was 62.6% and 32.7% in the HASS and CASS groups, respectively(P < 0.001). Platelet [odds ratio (OR) = 0.996, 95% confidence interval (CI) = 0.992–1.000, P = 0.028], positive pathogendetection (OR = 3.557, 95% CI = 1.307–9.684, P = 0.013), and multiple organ dysfunction syndrome (OR = 10.953, 95%CI = 1.974–60.775, P = 0.006) were risk factors for 28-day mortality in HASS patients. Lactate (OR = 1.104, 95% CI = 1.022–1.192, P = 0.012) and mechanical ventilation (OR = 8.114, 95% CI = 1.806–36.465, P = 0.006) were risk factors for 28-daymortality in patients with CASS.Conclusions The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between theHASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patientswith septic shock.