Background: Sepsis-associated liver injury (SALI) is a risk factor of poor outcome in patients with sepsis. The early warning biomarkers for identifying SALI remain poorly defined. Aims: To identify the potential predictors of occurrence of SALI in pediatric patients with sepsis. Methods: We retrospectively analyzed the sepsis database based on the medical records of patients admitted to the pediatric intensive care unit (PICU) in Shanghai Children's Hospital from July 2014 to June 2018. Patients' demographics, co-morbidities and laboratory variables were collected. Univariate and multivariate logistic analysis were used to explore risk factors of SALI, and receiver operating characteristic (ROC) curve analysis was used to evaluate their predictive significances for SALI occurrence. Results: Of 1,645 eligible patients, 1,147 patients were included, and 105 cases had SALI. The indexes including AST-to-platelet ratio index (APRI), γ-GT and lactate dehydrogenase (LDH) were independent risk factors for SALI. Moreover, APRI was powerful to predict SALI in children (AUC: 0.889, 95% CI : 0.851–0.927) with a sensitivity of 84.6 % and a specificity of 84.3 % at the cutoff point of 0.340. APRI was superior to LDH and not inferior to γ-GT for predicting SALI. Conclusion: APRI is an independent risk factor of SALI occurrence, and elevated APRI within 24 h after PICU admission (>0.340) is a potential predictor for SALI in children.

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.

IntroductionAcute 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 methodsRT-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 enrich-ment analysis (GSEA) was employed to explore the PDIA 3-associated pathways in AML. Western blotting was used for protein expression detection.ResultsPDIA3 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.ConclusionPDIA3 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.