End-organ damage from neonatal invasive fungal infection: a 14-year retrospective study from a tertiary center in China.

BACKGROUND: Invasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future. METHODS: The clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared. RESULTS: Included in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28, <32 weeks, and 37.7% with BW of 1000-1499 g. Candida albicans (C. albicans) was the most common Candida spp. in these neonates, accounting for 41.3% of all cases, followed by C. parapsilosis (30.5%) and C. glabrata (7.2%). EOD occurred in 40 (17.9%) of the 223 cases. Fungal meningitis was the most common EOD, accounting for 13.5% of the 40 EOD cases. There was no significant difference in the premature birth rate, delivery mode, GA and BW between EOD and NEOD groups, but the proportion of male infants with EOD was higher than that without. There was no significant difference in antenatal corticosteroid use, endotracheal intubation, invasive procedures, use of antibiotics, total parenteral nutrition, blood transfusion, postnatal corticosteroid use, fungal prophylaxis and the incidence of necrotizing enterocolitis between the two groups, but the proportion of C. albicans infection cases in EOD group was higher than that in NEOD group (57.5% vs. 37.7%). Compared with NEOD group, the proportion of cured or improved infants in EOD group was significantly lower (P < 0.05), and the number of infants who died or withdrew from treatment was larger (P < 0.05). CONCLUSIONS: Our retrospective study showed that preterm infants were prone to fungal infection, especially very preterm infants. C. albicans was the most common Candida spp. for IFI, and was a high-risk factor for EOD. EOD can occur in both full-term and premature infants, so the possibility of EOD should be considered in all infants with IFI.

CIRC_0012535 CONTRIBUTES TO LIPOPOLYSACCHARIDE-INDUCED FETAL LUNG FIBROBLAST APOPTOSIS AND INFLAMMATION TO REGULATE INFANTILE PNEUMONIA DEVELOPMENT BY MODULATING THE MIR-338-3P/IL6R SIGNALING.

ABSTRACT: Background: Infantile pneumonia is a respiratory infection disease, seriously threatening the life of neonatal patients. Circular RNA (circRNA) dysregulation is reported to be involved in pneumonia pathogenesis. Circ_0012535 was previously displayed to be upregulated in blood samples of patients with community-acquired pneumonia. However, circ_0012535's role in this disorder remains unclear. We thus aim to unveil the functions of circ_0012535 in infantile pneumonia. Methods: Fetal lung fibroblasts (WI38) treated with LPS were used as pneumonia cell models. Expression analysis for circ_0012535, miR-338-3p and IL6R was performed using quantitative real-time polymerase chain reaction. Cell counting kit 88), 5-ethynyl-2'-deoxyuridine, and flow cytometry assays were implemented for cell function detection. The release of inflammatory factors, and superoxide dismutase activity and malonaldehyde content were ascertained using commercial kits. The putative binding between miR-338-3p and circ_0012535 or IL6R was validated by dual-luciferase analysis, RIP analysis, and pull-down analysis. Results: Circ_0012535 was highly expressed in LPS-treated WI38 cells. Knockdown of circ_0012535 recovered LPS-inhibited cell viability and proliferation and attenuated LPS-induced cell apoptosis, cell cycle arrest, inflammation, and oxidative stress. Circ_0012535 bound to miR-338-3p and negatively regulated miR-338-3p expression. Inhibition of miR-338-3p reversed the role of circ_0012535 knockdown, thereby recovering LPS-induced WI38 cell apoptosis and inflammation. MiR-338-3p bound to IL6R 3'UTR, and circ_0012535 shared miR-338-3p binding site with IL6R. IL6R overexpression reversed the role of miR-338-3p, thereby recovering LPS-induced WI38 cell apoptosis and inflammation. Conclusion: Circ_0012535 supported LPS-induced WI38 cell apoptosis and inflammation to promote the progression of infantile pneumonia, and circ_0012535 functioned partly by targeting the miR-338-3p/IL6R signaling.

PCP can enhance dendritic cells to present the HBsAg peptide.

AIM: To investigate the influence of paraclorophenol (pCP) on dendritic cells loading and presenting HBsAg from peripheral blood monocytes of healthy volunteers identified as hepatitis B vaccine nonresponders. METHODS: The density gradient centrifugation was performed to isolate mononuclear cells from 10 hepatitis B vaccine nonresponders. The adherent monocytes were incubated with HBsAg adding rhGM-CSF and rhIL-4 in the presence of absence of pCP for 7 days. Then the supernatant was collected for ELISA assays. The culture medium system without pCP was used as negative control and without pCP or HBsAG was named blank control. the matured DCs were co-incubated with autologous T lymphocytes for 72h and the supernatant was also collected for ELISA assays. RESULTS: In the presence of pCP, the level of IL-12 in supernate (265.68± 16.21) ng/L was significantly higher than the negative control (168.76±10.01) ng/L (P<0.05) and blank control (87±5.79)ng/L (P<0.05); after co-incubated with autologous T lymphocytes for 3 days, the level of IFN-γ with pCP (773.04±32.73) mg/L was also significantly higher than the negative control (573.59±26.11) mg/L (P<0.05) ans blank control (362.81±24.27)mg/L (P<0.05). CONCLUSION: pCP can effectively enhance the dendritic cells loading and presenting HBsAg from peripheral blood monocytes of healthy volunteers identified as hepatitis B vaccine nonresponders, which also can dramatically increase te autologous T lymphocytes response.7