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The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In in vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored adenosine triphosphate (ATP) synthesis. Among the transcriptome sequencing data, the difference of CXCL5 (C-X-C motif chemokine ligand 5) was the most significant. Both high copper and ADR exposure can cause upregulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease. NEW & NOTEWORTHY: Cuproptosis induced by excessive copper accumulation leads to podocyte cytoskeleton damage by promoting mitochondrial dysfunction, and CXCL5 acts as an upstream signal mediating the occurrence of cuproptosis. [ABSTRACT FROM AUTHOR]

Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 μg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1β, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI. [ABSTRACT FROM AUTHOR]

Background: ACE2 plays a particular role in the changes in multiple organ functions. However, whether ACE2 expression differs at different ages and whether it plays a role in infection-related organ dysfunction remains unclear. Methods: Female and male C57BL/6 mice in four different age groups were included in this study. Immunohistochemical and Western blot analyses were performed to evaluate ACE2 expression characteristics in lung tissues. At the same time, we detected the changes of ACE2 in human blood of different ages and evaluated its clinical significance in sepsis-associated organ dysfunction (SAOD). Results: This study indicated that ACE2 is expressed differently in mouse lung tissues at four different ages (P < 0.05). The peak expression distribution of ACE2 in lung tissues was in the newborn and middle-aged cohorts (P < 0.05). Infants younger than one year had a significantly higher concentration of ACE2 in serum and enhanced susceptibility compared with other ages (P < 0.05). Serum APTT, D-dimer, LDH, and PCT, as well as ACE2 in sepsis and SAOD groups, were statistically significant (P < 0.05) and were related to an increased risk of SAOD. There was a positive correlation between ACE2 and D-dimer (P < 0.05). Conclusion: The levels of ACE2 expression varied in different age groups. It tends to be higher in infants and young children. This result suggests that young children are more susceptible to infection. Moreover, a cutoff value for the ACE2 level > 1551.15 pg/mL and D-dimer > 984.5 U/L should be considered a warning sign of infection-associated organ dysfunction and guide the clinician in evaluating the patient's multiple organ function. [ABSTRACT FROM AUTHOR]

Background/Aims: IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' untranslated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL). Methods: Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman. Cell functional studies included real-time PCR, cell culture and transfection and luciferase assays. Results: We found that rs6214 homozygous AA genotype and rs6218 homozygous CC genotype were significantly associated with increased risk of childhood ALL. In addition, rs6218 CC genotype was associated with increased level of IGF1 mRNA in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-miR-603 and hsa-miR-3941 in the 3'UTR of IGF1. Conclusion: Polymorphisms of rs6214 and rs6218 in the 3'UTR of IGF1 are associated with childhood ALL susceptibility, and the polymorphism of rs6218 is related with IGF1 expression at mRNA level. [ABSTRACT FROM AUTHOR]

Sepsis is a systemic inflammatory response syndrome caused by viral infection. The circulatory dysfunction caused by sepsis is also called septic shock or septic shock. The main characteristics are rapid onset, rapid changes, and involvement. Multiple organs in the body make diagnosis difficult, which seriously threatens the survival of patients. As many as one million people worldwide die every year because of SIRS, it is also the leading cause of death among children in hospital ICUs. This article is aimed at studying the clinical characteristics of severe sepsis in children and the risk factors for death. Based on the analysis of the pathogenesis of sepsis and the treatment of septic shock, 65 cases of children with PICU sepsis admitted to a hospital were selected. Data, to study its clinical characteristics and risk factors for death. The results of the study showed that despite the interaction among the removal factors of the three indexes of serum lactic acid value, PCIS level, and the number of organs involved in MODS, they are still related to the mortality of children with severe sepsis. [ABSTRACT FROM AUTHOR]

Activation of endothelial cells plays a key role in septic acute kidney injury (AKI). This study investigated the role of miRNA in endothelial-induced tubular cell injury in sepsis. Circulating endothelial cells (CECs) from septic AKI, non-septic AKI, septic non-AKI patients and healthy volunteers were isolated and cultured, and HK2 cells were exposed to CEC-conditioned medium. CEC-conditioned medium prepared from septic AKI patients led to cell shrinkage, decreased E-cadherin, the release of NAG and cell apoptosis in HK2 cells. TNF-α mediated the tubular cell injury induced by CEC-conditioned medium prepared from septic AKI patients. PCR array analysis detected that miR-107 was significantly increased in the CECs of septic AKI patients. MiR-107 was verified to target the 3′UTR of Dual-specificity phosphatase 7(DUSP7). Transfection of miR-107 ASO recovered the expression of DUSP7, suppressed the phosphorylation of ERK, and decreased the secretion of TNF-α in the CECs of septic AKI patients and in the peritubular endothelial cells of septic AKI mice. The inhibition of miR-107 prevented the decrease of E-cadherin, the release of NAG and cell apoptosis in HK2 cells exposed to CEC-conditioned medium prepared from septic AKI patients, and preserved the normal renal morphology and decreased the serum creatinine level in septic AKI mice. In conclusion, our study suggests that the increased miR-107 induces TNF-α secretion by targeting DUSP7 in endothelial cells, which may directly cause tubular cell injury in septic AKI. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the incidence, outcome, and prognostic factors of prolonged mechanical ventilation (PMV) in children in Mainland China., Methods: A prospective study was conducted in 11 pediatric intensive care units (PICUs) from May 1, 2021, to April 30, 2022. All pediatric patients on mechanical ventilation meeting the criteria for PMV were included in the study., Results: Out of 5,292 patients receiving mechanical ventilation, 278 children met the criteria for PMV (5.3%). After excluding case with incomplete data or lost to follow-up, the study included 250 patients. Among them, 115 were successfully weaned from mechanical ventilation, 90 died, and 45 were still on mechanical ventilation. The 6-month survival rate was 64%. The primary associated conditions of PMV were lower airway diseases (36%), central nervous system diseases (32%), and neuromuscular diseases (14%). The stepwise multiple logistic regression analysis indicated that the utilization of vasoactive agents and an elevated pediatric logistic organ dysfunction-2 (PELOD-2) score on the day of PMV diagnosis were significantly associated with an increased of PMV death. Specifically, the odds ratio (OR) for vasoactive agent use was 2.86; (95% CI: 0.15-0.84; P  = 0.018), and for the PELOD-2 score, it was 1.37; 95% CI: 1.17-1.61; P  < .001). Conversely, early rehabilitation intervention was negatively associated with the risk of PMV death (OR = 0.45; 95% CI: 0.22-0.93; P  = .032). Furthermore, the tracheotomy timing emerged as an independent predictor of failure to wean from PMV, with an OR of 1.08, (95% CI: 1.01-1.16; P   =  .030)., Conclusions: The study revealed a 5.3% incidence of PMV in children requiring mechanical ventilation in China. The use of vasoactive agents and a higher PELOD-2 score at PMV diagnosis were significantly associated with an increased risk of PMV death, whereas early rehabilitation intervention was identified as crucial for improving patient outcomes. The timing of tracheostomy was identified as a high-risk factor for failure to wean from mechanical ventilation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Zhang, Cai, Ming, Huang, Liu, Ren, Qu, Gao, Cheng, Zhang, Yang, Xu, Miao, Liu, Liu, Lu and Chen.)

Background: We aimed to analyze the levels and associations of SH2 domain-containing protein 1A (SH2D1A), immunoglobulins and T lymphocyte (TL) subsets in children with Epstein-Barr virus (EBV) infections., Methods: Sixty children with EBV infections admitted from January 2019 to January 2022 were selected, including 29 cases of infectious mononucleosis (IM group) and 31 cases of chronic active EBV infections (CAEBV group). Another 42 healthy children undergoing physical examination in the same period were selected as a control group. Their changes in SH2D1A, immunoglobulins and TL subsets (CD3+, CD4+ and CD8+) were compared., Results: The levels of CD3+, CD4+ and CD8+ in the IM group were higher than those of the control group (P < 0.05), while they were lower in the CAEBV group than those of the control and IM groups (P < 0.05). The levels of SH2D1A, signaling lymphocyte activation molecule (SLAM) and SLAM-associated protein (SAP) were significantly higher in the IM group than those in the control and CAEBV groups (P < 0.05). The CAEBV group had decreased protein expressions of SLAM and SAP compared with those of the IM group. SH2D1A was positively correlated with immunoglobulin A, immunoglobulin G and TL subsets (CD3+, CD4+ and CD8+) (P < 0.05)., Conclusions: Detecting SH2D1A, immunoglobulins and TLs contributes to the diagnosis and differentiation of IM and CAEBV.

Objective: To investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China., Methods: A prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017-October 2018). Data were collected and analyzed using the "in-hospital Utstein style." Neurological outcome was assessed with the Pediatric Cerebral Performance Category (PCPC) scale among children who had survived. Factors associated with the return of spontaneous circulation (ROSC) and survival at discharge were evaluated using multivariate logistic regression., Results: Among 11,599 admissions to PICU, 372 children (3.2%) had CPA during their stay; 281 (75.5%) received CPR, and 91 (24.5%) did not (due to an order of "Do Not Resuscitate" requested by their guardians). Cardiopulmonary disease was the most common reason for CPA (28.1% respiratory and 19.6% circulatory). The most frequent initial dysrhythmia was bradycardia (79%). In total, 170 (60.3%) of the total children had an ROSC, 91 had (37.4%) survived till hospital discharge, 28 (11.5%) had survived 6 months, and 19 (7.8%) had survived for 1 year after discharge. Among the 91 children who were viable at discharge, 47.2% (43/91) received a good PCPC score (1-3). The regression analysis results revealed that the duration of CPR and the dose of epinephrine were significantly associated with ROSC, while the duration of CPR, number of CPR attempts, ventricular tachycardia/ventricular fibrillation (VT/VF), and the dose of epinephrine were significantly associated with survival at discharge., Conclusion: The prevalence of CPA in critically ill children and adolescents is relatively high in China. The duration of CPR and the dose of epinephrine are associated with ROSC. The long-term prognosis of children who had survived after CPR needs further improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ding, Liu, Qian, Zeng, Wang, Chu, Chen, Chen, Duan, Jin, Huang, Lu, Guo, Shi, Huo, Su, Cheng, Yin, Xin, Sun, Zhao, Miao, Lou, Li, Jiang and Dong.)

Objective: The purpose of our study was to assess organ function in 102 patients with severe COVID-19 infections, using retrospective clinical analysis., Material and Methods: A retrospective analysis was conducted on 102 patients with severe COVID-19 infections. The patients were divided into a survival group ( n  = 73) and a non-survival group ( n  = 29) according to their prognosis. The age, sex, underlying diseases, clinical laboratory data within 48 h (routine blood tests, ALT, AST, TBIL, ALB, BUN, CR, D-Dimer, PT, APTT, FIB, F VIII:C, CK-MB, CK, and LDH), and ventilation status were collected. The organ functions of these severe COVID-19 patients were assessed by comparing the differences between the two groups., Results: AST, BUN, CR, CK-MB, LDH, and CK in the non-survival group were higher than those in the survival group, and the differences were statistically significant ( P  < 0.05). D-Dimer, PT, FIB, and F VIII:C in the non-survival group were higher than the values observed in the survival group, and the differences were statistically significant ( P  < 0.05). PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH predicted the area under the ROC curve (AUC) of the COVID19 endpoint events and were 0.721, 0.854, 0.867, 0.757, 0.699, 0.679, 0.715, 0.811, 0.935, and 0.802, respectively., Conclusion: The results showed that there were different degrees of damage to the liver, kidneys, blood coagulation, and heart function in the non-survival group. In addition, PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH had value in evaluating disease prognosis., (© 2020 Elsevier España, S.L.U. All rights reserved.)

Background: The mortality prediction scores were widely used in pediatric intensive care units. However, their performances were unclear in Chinese patients and there were also no reports based on large sample sizes in China. This study aims to evaluate the performances of three existing severity assessment scores in predicting PICU mortality and to identify important determinants. Methods: This prospective observational cohort study was carried out in eight multidisciplinary, tertiary-care PICUs of teaching hospitals in China. All eligible patients admitted to the PICUs between Aug 1, 2016, and Jul 31, 2017, were consecutively enrolled, among whom 3,957 were included for analysis. We calculated PCIS, PRISM IV, and PELOD-2 scores based on patient data collected in the first 24 h after PICU admission. The in-hospital mortality was defined as all-cause death within 3 months after admission. The discrimination of mortality was assessed using the area under the receiver-operating characteristics curve (AUC) and calibrated using the Hosmer-Lemeshow goodness-of-fit test. Results: A total of 4,770 eligible patients were recruited (median age 18.2 months, overall mortality rate 4.7%, median length of PICU stay 6 days), and 3,957 participants were included in the analysis. The AUC (95% confidence intervals, CI) were 0.74 (0.71-0.78), 0.76 (0.73-0.80), and 0.80 (0.77-0.83) for PCIS, PRISM IV, and PELOD-2, respectively. The Hosmer-Lemeshow test gave a chi-square of 3.16 for PCIS, 2.16 for PRISM IV and 4.81 for PELOD-2 ( p ≥ 0.19). Cox regression identified five predictors from the items of scores better associated with higher death risk, with a C-index of 0.83 (95%CI 0.79-0.86), including higher platelet (HR = 1.85, 95% CI 1.59-2.16), invasive ventilation (HR = 1.40, 1.26-1.55), pupillary light reflex (HR = 1.31, 95% CI 1.22-1.42) scores, lower pH (HR 0.89, 0.84-0.94), and extreme PaO 2 (HR 2.60, 95% CI 1.61-4.19 for the 1st quantile vs. 4th quantile) scores. Conclusions: Performances of the three scores in predicting PICU mortality are comparable, and five predictors were identified with better prediction to PICU mortality in Chinese patients., (Copyright © 2020 Zhang, Huang, Wang, Li, Miao, Zhang, Pan, Zhang, Zhu, Chen, Li, Su, Bi, Chen, Jin, Miao, Kong, Cheng, Chen, Yan, Yan and Lu.)

The goal of this paper is to report on the study of the mechanism of neural damage in neonatal cerebral cortex and hippocampus when hypoxic-ischemic brain damage (HIBD) occurs and the neural protective effects of simvastatin. One hundred forty-four 7-day-old SD rats of were randomly divided into four groups, i.e., sham operation group (sham group), normal saline control group (HIBD group), citicoline control group (CDPC group), and simvastatin-treated group. Each group was divided into six time points (0 h, 12 h, 24 h, 48 h, 72 h, and 7 days after HIBD or sham operation), and each time point included six rats. The expression of intercellular adhesion molecule-1 (ICAM-1) mRNA was determined semiquantitively by reverse transcription polymerase chain reaction (RT-PCR) in the cortex and hippocampus of neonatal rats at different times to determine the differences. The expression of ICAM-1 mRNA rose obviously 12 h after HIBD in the ischemic hemisphere, peaked at 24 h, and then decreased gradually. There was a remarkably lower expression in the CDPC group and simvastatin group compared with the HIBD group at 12 h, 24 h, 48 h, and 72 h. At 7 days, there was no significant difference between the simvastatin group and the sham group (P > 0.05), and at 72 h, simvastatin down-regulated the expression of ICAM-1 mRNA in cortex significantly more than did citicoline (P < 0.05). Both simvastatin and CDPC can relieve the damages of the brain in rats with HIBD. The protective mechanisms of simvastatin and citicoline are associated with their regulative effect on ICAM-1, and simvastatin is superior to citicoline.