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Background: Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death. Methods: Acute lung injury animal models were established using C57BL/6 and Ager gene knockout (Ager−/− mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test. Results: The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager−/− mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway. Conclusion: RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells. [ABSTRACT FROM AUTHOR]

Background: Continuous renal replacement therapy (CRRT) has been considered as an adjuvant therapy for sepsis. However, the novel biomarker to evaluate the benefits of CRRT is limited. The aim of this study was to explore the novel biomarkers involved in the impact of CRRT in pediatric sepsis. Methods: The serum proteomic profiles on the 7th day after CRRT (CRRT 7th day) compared with before CRRT (CRRT 1st day) was determined in 3 children with sepsis as a discovery set. The screened candidates were confirmed in the validation cohort including patients received CRRT (CRRT group) and without CRRT (non-CRRT group). We defined that pediatric sequential organ failure assessment score (pSOFA) in pediatric patients with sepsis decreased by 2 points or more on the CRRT 1st day compared with CRRT initiation as CRRT responders. The changes of serum biomarkers were compared between CRRT responders and CRRT non-responders. Moreover, correlation analysis was further conducted in pediatric sepsis. Results: A total of 145 differentially expressed proteins were found according to the serum proteomics profiles. By visualizing the interaction between the differential proteins, 6 candidates (Lysozyme C [LYZ], Leucine-rich alpha-2-glycoprotein [LRG1], Fibromodulin [FMOD], Alpha-1-antichymotrypsin [SERPINA3], L-selectin [SELL], Monocyte differentiation antigen CD14 [CD14]) were screened. In the validation cohort, serum levels of LYZ and LRG1 showed a higher trend on the CRRT 7th day than that on the 1st day in the non-CRRT group. However, the changes in levels of LYZ and LRG1 on the 7th day was significant in the CRRT group (p = 0.016, p = 0.009, respectively). Moreover, the levels of LYZ and LRG1 on the CRRT 7th day in the CRRT group were significantly higher than that in the non-CRRT group (p < 0.001, p = 0.025). Decreased levels of CD14 were associated with sepsis recovery, but not associated with CRRT. There were no significantly difference in serum FMOD, SERPINA3, and SELL levels. Importantly, serum LYZ and LRG1 levels changed in CRRT responders, but not CRRT non-responders. Further analysis indicated that serum LYZ levels were correlated to total platelet counts, aspartate aminotransferase (ALT), alanine aminotransferase (AST), and albumin levels, and serum LRG1 level were correlated to total platelet count and TBIL levels on the 1st day in the CRRT group. Protein–protein interaction network analysis displayed that serum LYZ and LRG1 were involved in the process of inflammatory response, leucocytes adhesion to vascular endothelial cell, as well as complement activation. Conclusion: Elevated serum LYZ and LRG1 levels are associated with clinical benefits of CRRT during sepsis. [ABSTRACT FROM AUTHOR]

Background: To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients.Methods: A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate.Results: In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO2/FiO2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO2/FiO2 <61 mmHg or an OI >43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes.Conclusions: ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia. [ABSTRACT FROM AUTHOR]

Background. Systemic inflammatory response and vascular endothelial cell injury during sepsis lead to coagulopathy. Fibrinogen has been reported as a biomarker of coagulopathy; however, the prognostic value of fibrinogen remains undefined in pediatric patients with sepsis. The aim of this study was to assess fibrinogen level on pediatric intensive care unit (PICU) admission and to elucidate the relationship between fibrinogen levels and in-hospital mortality in children with sepsis. Methods. We conducted a database study. The sepsis database was divided into a training set (between July 2014 and June 2018) and a validation set (from July 2018 to June 2019). The clinical and laboratory parameters on PICU admission and in-hospital mortality in sepsis database were collected and analyzed. Results. A total of 819 pediatric patients were included from database as a training set. The overall hospital mortality was 12.1% (99/819). The fibrinogen levels were significantly lower in nonsurvivors than survivors. Multivariate logistic regression analysis showed significant associations between fibrinogen, lactate level, and hospital mortality (fibrinogen: odds ratio (OR), 0.767 (95% CI: 0.628-0.937), P = 0.009 ; lactate: OR, 1.346 (95% CI: 1.217-1.489), P < 0.001 , respectively), which was confirmed in a validation set (0.616 [95% CI: 0.457-0.829], P = 0.001 ; 1.397 [95% CI: 1.245-1.569], P < 0.001 , respectively). The hospital mortality of patients with fibrinogen < 1 g / L , 1-2 g/L, 2-3 g/L, or over 3 g/L displayed an obvious difference (62.5% vs. 27.66% vs. 18.1% vs. 4.2%, respectively). Furthermore, the area under the receiver operating characteristic curve (ROC) for fibrinogen in predicting hospital mortality was 0.780 (95% CI: 0.711-0.850) in pediatric patients with sepsis. Conclusions. Fibrinogen is a valuable prognostic biomarker for pediatric sepsis. The level of fibrinogen lower than 2 g/L on PICU admission is closely related to the greater risk of hospital death in pediatric sepsis. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormone plays an important role in the adaptation of metabolic function to critically ill. The relationship between thyroid hormone levels and the outcomes of septic shock is still unclear. The aim of this study was to assess the predictive value of thyroid hormone for prognosis in pediatric septic shock. Methods: We performed a prospective observational study in a pediatric intensive care unit (PICU). Patients with septic shock were enrolled from August 2017 to July 2019. Clinical and laboratory indexes were collected, and thyroid hormone levels were measured on PICU admission. Results: Ninety-three patients who fulfilled the inclusion criteria were enrolled in this study. The incidence of nonthyroidal illness syndrome (NTIS) was 87.09% (81/93) in patients with septic shock. Multivariate logistic regression analysis showed that T4 level was independently associated with in-hospital mortality in patients with septic shock (OR: 0.965, 95% CI: 0.937–0.993, p = 0.017). The area under receiver operating characteristic (ROC) curve (AUC) for T4 was 0.762 (95% CI: 0.655–0.869). The cutoff threshold value of 58.71 nmol/L for T4 offered a sensitivity of 61.54% and a specificity of 85.07%, and patients with T4 < 58.71 nmol/L showed high mortality (60.0%). Moreover, T4 levels were negatively associated with the pediatric risk of mortality III scores (PRISM III), lactate (Lac) level in septic shock children. Conclusions: Nonthyroidal illness syndrome is common in pediatric septic shock. T4 is an independent predictor for in-hospital mortality, and patients with T4 < 58.71 nmol/L on PICU admission could be with a risk of hospital mortality. [ABSTRACT FROM AUTHOR]

Background. Systemic inflammatory response and vascular endothelial cell injury during sepsis lead to coagulopathy. Fibrinogen has been reported as a biomarker of coagulopathy; however, the prognostic value of fibrinogen remains undefined in pediatric patients with sepsis. The aim of this study was to assess fibrinogen level on pediatric intensive care unit (PICU) admission and to elucidate the relationship between fibrinogen levels and in-hospital mortality in children with sepsis. Methods. We conducted a database study. The sepsis database was divided into a training set (between July 2014 and June 2018) and a validation set (from July 2018 to June 2019). The clinical and laboratory parameters on PICU admission and in-hospital mortality in sepsis database were collected and analyzed. Results. A total of 819 pediatric patients were included from database as a training set. The overall hospital mortality was 12.1% (99/819). The fibrinogen levels were significantly lower in nonsurvivors than survivors. Multivariate logistic regression analysis showed significant associations between fibrinogen, lactate level, and hospital mortality (fibrinogen: odds ratio (OR), 0.767 (95% CI: 0.628-0.937), P = 0.009 ; lactate: OR, 1.346 (95% CI: 1.217-1.489), P < 0.001 , respectively), which was confirmed in a validation set (0.616 [95% CI: 0.457-0.829], P = 0.001 ; 1.397 [95% CI: 1.245-1.569], P < 0.001 , respectively). The hospital mortality of patients with fibrinogen < 1 g / L , 1-2 g/L, 2-3 g/L, or over 3 g/L displayed an obvious difference (62.5% vs. 27.66% vs. 18.1% vs. 4.2%, respectively). Furthermore, the area under the receiver operating characteristic curve (ROC) for fibrinogen in predicting hospital mortality was 0.780 (95% CI: 0.711-0.850) in pediatric patients with sepsis. Conclusions. Fibrinogen is a valuable prognostic biomarker for pediatric sepsis. The level of fibrinogen lower than 2 g/L on PICU admission is closely related to the greater risk of hospital death in pediatric sepsis. [ABSTRACT FROM AUTHOR]

Background. Sepsis induces the release of lipid mediators, which control both lipid metabolism and inflammation. However, the role of serum apolipoprotein A-V (ApoA5) in sepsis is poorly understood in pediatric patients. Methods. ApoA5 was screened from serum proteomics profile in lipopolysaccharide- (LPS-) treated mice for 2 h, 24 h, and controls. Then, we conducted a prospective pilot study, and patients with sepsis admitted to a pediatric intensive care unit (PICU) were enrolled from January 2018 to December 2018. Serum ApoA5 levels on PICU admission were determined using enzyme-linked immunosorbent assays (ELISA). Blood samples from 30 healthy children were used as control. The correlation of ApoA5 with the clinical and laboratory parameters was analyzed. Logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to investigate the potential role of serum ApoA5 as a prognostic predictor for PICU mortality in pediatric patients with sepsis. Results. A total of 101 patients with sepsis were enrolled in this study. The PICU mortality rate was 10.9% (11/101). Serum ApoA5 levels on PICU admission were significantly lower in nonsurvivors with sepsis compared with survivors (P = 0.009). In subgroup analysis, serum levels of ApoA5 were significantly correlated with sepsis-associated multiple organ dysfunction syndrome (MODS) (P < 0.001), shock (P = 0.002), acute kidney injury (AKI) (P < 0.001), acute liver injury (ALI) (P = 0.002), and gastrointestinal (GI) dysfunction (P = 0.012), but not respiratory failure, brain injury, and pathogenic species (all P > 0.05). Correlation analyses revealed significant correlations of serum ApoA5 with Ca2+ concentration. Remarkably, the area under ROC curve (AUC) for serum ApoA5 levels on PICU admission was 0.789 for prediction of PICU mortality with a sensitivity of 75% and a specificity of 84.5% at a threshold value of 822 ng/mL. Conclusions. Serum ApoA5 level is associated with sepsis-associated shock, AKI, ALI, GI dysfunction, or MODS in children. Moreover, the findings of the present study suggest a prognostic value of ApoA5 in children with sepsis, and lower serum ApoA5 than 822 ng/mL predicts worse outcome in pediatric sepsis. [ABSTRACT FROM AUTHOR]

Specifically, Figure 2Ba, HL60 cells, PCA (1 µM), appears to have been duplicated with the same image for Figure 3Ba, U937 cells, PCA (1 µM), and Figure 3Ba, U937 cells, PCA (2 µM), which has been flipped. This retraction relates to this paper Ye QD, Liao XL, Fu P, Dou JY, Chen K, Jiang H. I Onco Targets Ther i . 2016;9:6953-6963. [Extracted from the article]

Introduction: Acute myeloid leukemia (AML) is a common malignancy of the hematopoietic system. In bone marrow samples of AML patients, PDIA3 expression was higher than that in the samples of healthy controls. We aimed at exploring the effect of PDIA3 siRNA on proliferation, apoptosis, migration, and invasion of AML HL-60 and HEL cells. Materials and methods: RT-PCR was performed to identify PDIA3 expression. Cell proliferation was assessed by MTT. Flow cytometry analysis and transwell were used to detect cell apoptosis, migration and invasion. Gene set enrichment analysis (GSEA) was employed to explore the PDIA 3-associated pathways in AML. Western blotting was used for protein expression detection. Results: PDIA3 siRNA significantly inhibited the proliferation of AML cells at 24 and 48 h. PDIA3 siRNA notably enhanced the percentage of apoptotic cells. The migration and invasion abilities of HL-60 and HEL cells in the PDIA3 siRNA group were significantly suppressed compared with those in the control and siNC groups. GSEA of the Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways could be correlated with PDIA3 expression; this was further confirmed in AML cells by Western blotting. MAPK signaling was also blocked by PDIA3 siRNA. Conclusion: PDIA3 siRNA effectively enhanced apoptosis, and suppressed proliferation, invasion, and migration of AML cells by regulating oxidative phosphorylation and amino sugar and nucleotide sugar metabolism pathways, and MAPK signaling, which can provide novel therapeutic targets for AML. [ABSTRACT FROM AUTHOR]