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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.

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.)

Objective: To determine the risk factors for developing severe pneumonia in children under 5 years old with pneumonia., Methods: A case-control study was conducted 246 children with pneumonia between 2 and 59 months old who were admitted to the department of emergency of the Children's Hospital of Nanjing Medical University from May 2019 to May 2021 were enrolled. The children with pneumonia were screened according to the diagnostic criteria of the World Health Organization (WHO). Case information of the children was reviewed to obtain relevant socio-demographic, nutritional status and potential risk factors. The independent risk factors for severe pneumonia were analyzed by univariate analysis and multivariate Logistic regression respectively., Results: Among the 246 patients with pneumonia, 125 were male and 121 were female. The average age was (21.0±2.9) months, 184 children with severe pneumonia. The results of population epidemiological characteristics showed that there were no significant differences in gender, age and place of residence between the severe pneumonia group and the pneumonia group. Prematurity, low birth weight, congenital malformation, anemia, length of intensive care unit (ICU) stay, nutritional support, treatment delay, malnutrition, invasive treatment, history of respiratory infection were all related factors affecting the occurrence of severe pneumonia (severe pneumonia group vs. pneumonia group: the proportion of premature infants was 9.52% vs. 1.23%, low birth weight was 19.05% vs. 6.79%, congenital malformation was 22.62% vs. 9.26%, anemia was 27.38% vs. 16.05%, length of ICU stay < 48 hours was 63.10% vs. 38.89%, enteral nutritional support was 34.52% vs. 20.99%, treatment delay was 42.86% vs. 29.63%, malnutrition was 27.38% vs. 8.64%, invasive treatment was 9.52% vs. 1.85%, respiratory tract infection history was 67.86% vs. 40.74%, all P > 0.05). However, breastfeeding, type of infection, nebulization, use of hormones, use of antibiotics, etc. were not risk factors affecting severe pneumonia. Multivariate Logistic regression analysis showed that history of premature birth, low birth weight, congenital malformation, treatment delay, malnutrition, invasive treatment, and history of respiratory infection were independent risk factors for severe pneumonia [history of premature birth: odds ratio (OR) = 2.346, 95% confidence interval (95%CI) was 1.452-3.785; low birth weight: OR = 15.784, 95%CI was 5.201-47.946; congenital malformation: OR = 7.135, 95%CI was 1.519-33.681; treatment delay: OR = 11.541, 95%CI was 2.734-48.742; malnutrition: OR = 14.453, 95%CI was 4.264-49.018; invasive treatment: OR = 6.373, 95%CI was 1.542-26.343; history of respiratory infection: OR = 5.512, 95%CI was 1.891-16.101, all P < 0.05]., Conclusions: Premature birth history, low birth weight, congenital malformation, delayed treatment, malnutrition, invasive treatment, and history of respiratory infection are independent risk factors for severe pneumonia in children under 5 years old.

Objective: To explore the clinical application value of the continuous blood purification (CBP) technology in pediatric intensive care unit (ICU)., Methods: A retrospective study was conducted. All CBP patients admitted to pediatric ICU of Children's Hospital of Nanjing Medical University from 2015 to 2017 were enrolled. The disease diagnosis, CBP treatment mode, catheter placement, anticoagulation way, treatment time and adverse reactions were summarized and analyzed., Results: (1) A total of 203 children were included, male accounted for 59.1%; age 37 days to 14 years old, with an average of (4.52±3.60) years old; weight 3.3-68.0 kg, with an average of (21.38±13.77) kg. (2) There were a total of 660 CBP treatments, with an average of 3.25 times per person. The main treatment modes of CBP were plasma exchange (PE, 38.64%), and followed by continuous veno-venous hemodiafiltration (CVVHDF, 38.64%), hemoperfusion (HP, 16.51%) and continuous veno-venous hemofiltration (CVVH, 6.21%). (3) Central venous catheterization was mainly placed in the right internal jugular vein (90.64%), followed by the right femoral vein (5.42%) and the left femoral vein (3.94%). (4) Heparin sodium was the main anticoagulant in pipeline filters (84.73%), followed by low molecular weight heparin calcium (11.33%), sodium citrate and non-anticoagulant (both 1.97%). Mixed anticoagulants were used 21 children. (5) Primary diseases included poisoning (26.11%), liver failure (25.62%), sepsis (12.32%), shock after cardiopulmonary resuscitation (11.82%), acute respiratory distress syndrome (ARDS, 8.37%), central nervous system diseases (5.41%) and metabolic diseases (4.93%). The lowest efficacy of CBP was metabolic diseases, with mortality rate of 60.00%; followed by ARDS, shock after cardiopulmonary resuscitation, sepsis and liver failure, with mortality was 58.82%, 41.67%, 36.00% and 32.69%, respectively. The length of hospitalization stay of children with central nervous system diseases was (30.89±15.13) days. (6) Adverse events of CBP treatment included uncontrollable restlessness (2.88%), hypotension (1.82%), allergic rash (1.21%), catheterization and pipeline coagulation (1.21%), filter coagulation (1.06%), decreased heart rate and oxygen saturation (0.76%); CBP was stopped in 8 children due to cardiac arrest during the treatment., Conclusions: At present, the application of CBP technology in pediatric ICU is universal, and it is an important way to rescue critical illness.