Xueyun Ren

Background: Acute myocardial infarction (AMI) is a critical and fatal cardiovascular condition. The role of cuproptosis as an emerging mechanism in the pathogenesis of AMI remains to be fully elucidated. Methods: Patient data were acquired from the Gene Expression Omnibus database. Differential expression analysis was performed on cuproptosis-related genes (CRGs). LASSO regression was employed to identify key CRGs and develop a diagnostic classification model for AMI. Weighted gene co-expression network analysis was performed to investigate key modules associated with the disease and its molecular classification. Subsequently, machine learning techniques were used to identify critical genes within these modules. The diagnostic efficacy of these genes for AMI was assessed using receiver operating characteristic analysis. The functions of the identified key genes were ultimately validated at the cellular level. Results: Six characteristic CRGs were selected via LASSO regression. The AMI diagnostic classification model based on these CRGs demonstrated superior performance. Patients were classified into two subtypes related to cuproptosis, revealing significant differences in enrichment pathways between these subtypes. SYTL3, SCML1, and PMAIP1 were identified as key genes for AMI, with area under the curves of 0.813, 0.795, and 0.873, respectively. Knocking down PMAIP1 expression reduced intracellular copper levels in hypoxia-induced HUVECs. Conclusions: This study clarifies the role of cuproptosis in AMI and highlights the potential involvement of PMAIP1, providing a theoretical basis for further investigation into cuproptosis in AMI.

Staphylococcus aureus is a major pathogen responsible for both community-acquired and hospital-acquired infections. However, disseminated infections compli

Rationale: Weaver syndrome is a rare congenital overgrowth disorder characterized by a wide spectrum of clinical manifestations that often overlap with other overgrowth syndromes. It is primarily caused by pathogenic variants in the Enhancer of Zeste Homolog 2 ( EZH2 ) gene on chromosome 7q36.1. Globally, fewer than 70 cases have been reported, with only a few documented in the Chinese population. Patient concerns: We report a 13-day-old Chinese male infant, born with macrosomia (birth weight: 5.04 kg), who was admitted for persistent neonatal jaundice. Physical examination and subsequent follow-up revealed accelerated postnatal growth and characteristic craniofacial features, including a broad forehead, hypertelorism, epicanthal folds, a flat nasal bridge, and low-set ears. His length, weight, and head circumference consistently plotted above the 97th percentile for his age. Additional findings included large hands and feet. Diagnoses: The child was ultimately diagnosed with “Weaver syndrome.” Interventions: DNA nanoballs were prepared with a universal sequencing reaction kit and subjected to paired-end sequencing on the MGISEQ-2000 platform. The resulting reads were aligned to the human reference genome hg19 (GRCh37). After removing PCR duplicates, single nucleotide polymorphisms and insertions/deletions were identified and annotated against established variant databases. The potential pathogenicity of the identified variants and their structural impact on the protein were evaluated using computational prediction tools. This analysis revealed a missense variant in the EZH2 gene (NM_004456.4:c.2050C>T) in the proband, resulting in an arginine-to-cysteine substitution at codon 684 (p.Arg684Cys). In accordance with American College of Medical Genetics and Genomics guidelines, this variant was classified as pathogenic. Subsequent Sanger sequencing confirmed it as a de novo mutation. Outcomes: The patient received multidisciplinary guidance for neurodevelopmental, speech, and behavioral therapy. He remains under regular follow-up to monitor his growth and development. Lessons: This report documents a new case of Weaver syndrome in China harboring a de novo EZH2 mutation, expanding the genotypic and phenotypic spectrum of this disorder in the Chinese population. Our findings underscore the critical role of genetic testing in achieving a definitive diagnosis for rare overgrowth syndromes, facilitating early intervention and appropriate management.

Acute kidney injury (AKI) is a prevalent and critical complication in pediatric patients, severely influencing both survival outcomes and quality of life. This research seeks to evaluate the prognostic value of the lactate/albumin ratio (LAR) in predicting short-term outcomes for children diagnosed with AKI. A retrospective analysis was conducted using data from the Pediatric Intensive Care database, covering the period from 2010 to 2018. The relationship between the LAR and in-hospital mortality was explored using smoothing curve fitting, multivariate logistic regression, and Kaplan-Meier survival analysis. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive capability of LAR for in-hospital mortality. A total of 631 pediatric patients with AKI were included in this study. Smoothing curve fitting revealed a nearly linear positive association between the LAR and in-hospital mortality. Multivariate logistic regression analysis identified LAR as an independent predictor of in-hospital mortality (OR 2.58, 95% CI 1.85–3.59). Kaplan-Meier survival analysis showed that patients with a higher LAR had a significantly greater 30-day mortality rate compared to those with lower LAR values. ROC curve analysis demonstrated an area under the curve of 0.85 (95% CI 0.80–0.90). At the optimal cutoff value of 0.80, the sensitivity was 80.42%, specificity was 77.97%, and accuracy was 80.19%. These results suggest that LAR is a promising prognostic indicator of mortality in pediatric patients with AKI, and could serve as an early indicator of risk stratification.

Background Neonatal sepsis is characterized by an excessive immune response, often leading to multiple organ failure, including cardiac injury, and is a major cause of morbidity and mortality in newborns. Understanding the molecular mechanisms of sepsis-induced cardiac injury is crucial for developing therapeutic strategies. Objective To investigate transcriptomic changes and identify potential altered genes associated with cardiac injury in a neonatal sepsis model. Methods A neonatal sepsis model was established by cecal slurry injection. RNA sequencing analysis was performed on cardiac tissues from sepsis and control groups, followed by functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Interaction networks among mRNA, lncRNA, circRNA, and miRNA were constructed, and key regulatory genes were identified through protein–protein interaction (PPI) analysis. Results A total of 1537 differentially expressed mRNAs, 287 lncRNAs, and 730 circRNAs were identified. Functional analysis revealed significant involvement in immune response and inflammatory regulation. PPI network analysis identified six key genes—Ccl5, Il-6, Pole, Mcm2, Mcm5, Mcm10—that were significantly expressed in sepsis-induced cardiac tissue. Additionally, lncRNAs and circRNAs were found to participate in myocardial injury by regulating immune and inflammatory pathways. Conclusions This study identified six key genes involved in immune and inflammatory responses, playing critical roles in sepsis-induced cardiac injury in neonates. These findings provide new insights into the pathogenesis of sepsis-induced cardiac injury and offer potential therapeutic targets.

Introduction: Our study investigated the association between hematocrit in the first two hours (HCT2h) of life and retinopathy of prematurity (ROP). Methods: Data were obtained from an observational study of the DRYAD database. The study was conducted at the Santa Clara Valley Medical Center (SCVMC). Data on preterm babies whose gestational age (GA) was < 34 weeks were collected prospectively from January 2008 to February 2014. Logistic regression was applied to explore the association between HCT2h and ROP. Results: A total of 326 very preterm infants born at or earlier than 34 weeks were included. The incidence of any ROP was 23.9%, and the incidence of severe ROP was 4.6%. The HCT2h, birth weight, GA, Apgar1 min, and Apgar5 min of any ROP group were significantly lower than those of preterm babies without ROP (p < 0.001). Sex differences, the rate of multiples, and delivery mode between the two groups were not statistically significant (p > 0.05). We classified HCT2h into three levels, and after multivariate logistic regression, we found that high HCT2h remained a significant protective factor against ROP (p < 0.001). Through subgroup analysis, we observed that among preterm infants with a GA of 28 weeks or more, there was a significant inverse association between a 1% increase in HCT2h and a 17% reduction in the occurrence of ROP. Conclusion: We found that HCT2h may be an effective biomarker for identifying the risk of ROP of very preterm infants born between 28 and 34 weeks of gestation. Trial registration: This was a retrospective study and the data were from the DRYAD database. Santa Clara Valley Medical Center’s (SCVMC) ethical committee reviewed and approved the studies involving human participants. Informed consent was waived for this study. We did not perform any extra interventions.

Objectives Identifying high-risk paediatric patients with a poor prognosis and providing timely and adequate treatment are critical. This study aimed to evaluate the effects of different types of cardiac enzyme spectrum within 24 hours of admission on the short-term prognosis of patients in paediatric intensive care units. Design A retrospective study. Setting A single-centre, tertiary care hospital in China, with patient data from 2010 to 2018. Participants A total of 4343 critically ill children were enrolled. Intervention None. Primary and secondary outcome measures The main outcome measure was in-hospital mortality, which was defined as death from any cause during hospitalisation. The secondary outcome was 30-day mortality, intensive care unit (ICU) length of stay (LOS) and total LOS. Results Using the local polynomial regression fitting method, an approximately linear increase in in-hospital mortality was detected for creatine kinase (CK), creatine kinase MB (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Among the different types of cardiac enzyme spectrum, LDH had the highest area under the curve value (0.729), followed by AST (0.701), CK-MB (0.613) and CK (0.557). The Kaplan‒Meier analysis showed that the patients in the high LDH group had higher 30-day mortality. The multivariate logistic regression revealed that high LDH was independently associated with in-hospital mortality (OR 2.45, 95% CI 1.84 to 3.24). After propensity score matching (PSM) and sensitivity analysis, the results remained consistent. Conclusions LDH is a reliable outcome predictor in critically ill children, including those with various comorbidities.

Objective: Identifying high-risk children with poor prognoses during the early stages of sepsis and providing timely and appropriate interventions are imperative. The objective of this study was to develop a prognostic prediction model for pediatric sepsis utilizing the neutrophil to lymphocyte and platelet ratio (NLPR). Methods: A multivariable logistic regression analysis was conducted to investigate the association between the NLPR and in-hospital mortality among septic children upon admission. To minimize the potential confounding factors that could introduce bias, a propensity score matching analysis was employed. Subsequently, a nomogram prediction model was developed to assess the risk of in-hospital mortality in septic children, incorporating the NLPR as a key factor. The performance of this prediction model was then evaluated. Results: A total of 230 septic children were enrolled in the study. Multivariate logistic regression analysis revealed that the NLPR was an independent risk factor for in-hospital mortality, with an odds ratio of 8.31 (95% CI 3.69– 18.68). The finding remained consistent after propensity score matching analysis. A nomogram prediction model was developed that incorporates the NLPR, arterial blood lactate level, and Pediatric Critical Illness Score (PCIS). Among the various models, this nomogram exhibited the highest area under the curve (AUC) value of 0.831. The calibration curve demonstrated good agreement between the predicted and observed outcomes. Decision curve analysis indicated that the prediction model outperformed the PCIS. Internal validation of the model yielded an AUC value of 0.824 and a kappa value of 0.420, indicating its reliability and accuracy. Conclusion: The NLPR serves as an independent risk factor for in-hospital mortality among septic children. The nomogram prognostic prediction model could effectively guide clinicians in accurately predicting the prognosis of septic children, thus enabling timely and effective treatment interventions.

Given the critical role of immune cells and their responses in sepsis pathogenesis, this study aimed to evaluate the prognostic significance of various immune cell ratios in septic children through the collection and analysis of clinical data. Clinical data were collected from septic children admitted to the pediatric intensive care unit (PICU) of Shenzhen Children’s Hospital between January 2019 and September 2021. The peripheral blood immune cell ratios included the neutrophil to lymphocyte ratio (NLR), the derived neutrophil to lymphocyte ratio (dNLR), the neutrophil to lymphocyte and platelet ratio (NLPR), the monocyte to lymphocyte ratio (MLR), and the platelet to lymphocyte ratio (PLR). To investigate the associations between these immune cell ratios and mortality, we utilized the locally weighted scatterplot smoothing (LOWESS) method, receiver operating characteristic (ROC) analysis, and Kaplan‒Meier (K‒M) analysis. A total of 230 septic children were enrolled in the study. When comparing the immune cell ratios between the deceased and surviving groups, all ratios except for the PLR were elevated in the deceased group. Using the LOWESS method, we observed that the MLR, NLR, dNLR, and NLPR exhibited an approximately linear association with in-hospital mortality. Among the various immune cell ratios, the NLPR exhibited the highest AUC of 0.748, which was statistically comparable to that of the Pediatric Critical Illness Score (PCIS) (0.748 vs. 0.738, P = 0.852). The NLR (0.652), MLR (0.638), and dNLR (0.615) followed in terms of AUC values. K‒M analysis revealed that children with elevated MLR, NLR, dNLR, and NLPR exhibited increased 30-day mortality. The predictive capacity of the NLPR is comparable to that of the PCIS, suggesting that the NLPR has potential as a robust prognostic indicator for septic children.