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; Eftud2f/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.

Development and validation of equations for conversion from DAS28ESR and DAS28CRP to the SDAI in patients with rheumatoid arthritis.

INTRODUCTION: Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate (DAS28ESR), DAS28 with C-reactive protein (DAS28CRP), and simplified disease activity index (SDAI) are widely used to assess disease activity as low, moderate, or high or in remission in patients with rheumatoid arthritis (RA). However, these indicators can generate inconsistent results, influencing treatment decisions and limiting comparisons across studies. We aimed to establish equations for conversion from DAS28ESR and DAS28CRP to SDAI. METHODS: We conducted a retrospective study, including 933 outpatients who were simultaneously assessed using DAS28ESR, DAS28CRP, and SDAI. The patients were divided into a training set (70%) and a validation set (30%). We developed equations to convert DAS28ESR and DAS28CRP values into SDAI values by bisquare-weighted robust regression to obtain SDAI-DAS28ESR and SDAI-DAS28CRP. In addition to using kappa values to assess consistency, differences in disease activity classification between SDAI-DAS28ESR and SDAI-DAS28CRP were examined by the Stuart-Maxwell test and the Bowker test. RESULTS: Two quadratic equations were developed as follows: SDAI-DAS28ESR = 1.168 × (DAS28ESR)^2 - 2.432 × (DAS28ESR) + 2.649 and SDAI-DAS28CRP = 1.2 × (DAS28CRP)^2 - 0.3522 × (DAS28CRP) - 0.6014. After applying the equations, the Stuart-Maxwell test and the Bowker test were no longer significant between SDAI-DAS28ESR and SDAI or between SDAI-DAS28CRP and SDAI. The kappa values increased from 0.57 to 0.73 between SDAI-DAS28ESR and SDAI and 0.76 to 0.86 between SDAI-DAS28CRP and SDAI. CONCLUSION: SDAI-DAS28ESR and SDAI-DAS28CRP are interchangeable with the SDAI on the group level, which will facilitate comparisons among studies. In addition, the equations improved consistency between indicators. Key Points • There is disagreement in assessing disease activity in patients with rheumatoid arthritis between Disease Activity Score-28 (DAS28) with erythrocyte sedimentation rate (DAS28ESR), DAS28 with C-reactive protein (DAS28CRP), and simplified disease activity index (SDAI). • We developed and validated two quadratic equations to convert DAS28ESR and DAS28CRP into SDAI. We found there was no longer significant difference in disease activity between indicators after applying the equations. • This work may allow comparisons across studies which use different indicators.

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

BACKGROUND: We explored the differences in baseline characteristics, pathogens, complications, outcomes, and risk factors between children with hospital-acquired septic shock (HASS) and community-acquired septic shock (CASS) in the pediatric intensive care unit (PICU). METHODS: This retrospective study enrolled children with septic shock at the PICU of Beijing Children's Hospital from January 1, 2016, to December 31, 2019. The patients were followed up until 28 days after shock or death and were divided into the 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/oncologic diseases, mainly with Gram-negative bacterial bloodstream infections (47.3%). Additionally, 67.7% (n = 207) of CASS patients had no obvious underlying disease, and most experienced Gram-positive bacterial infections (30.9%) of the respiratory or 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 pathogen detection (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-day mortality in patients with CASS. CONCLUSIONS: The underlying diseases, pathogens, complications, prognosis, and mortality rates varied widely between the HASS and CASS groups. The predictors of 28-day mortality were different between HASS and CASS pediatric patients with septic shock.

[Prevalence and prevention of common nutritional risks in children after earthquake].

Children have been identified as the most nutritionally vulnerable group when disaster happens. The most common nutritional risks include protein-energy malnutrition, iron-deficiency anemia, and trace element deficiency in children after earthquake. During the disaster relief, effective nutritional interventions should be performed according to the nutritional conditions of children in the affected area, so as to prevent the common nutritional risks. Timely diagnosis and treatment should be provided for children at a high risk of malnutrition.