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BACKGROUND: The severity of complications after hematopoietic stem cell transplantation (HSCT) is dictated by the degree of immune reconstitution. However, the connection between immune reconstitution and the prognosis of pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. Therefore, the aim of this study was to evaluate the impact of lymphocyte subsets in children diagnosed with refractory or relapsed acute myeloid leukemia (R/R-AML) after allo-HSCT. METHODS: We retrospectively investigated the prognosis and lymphocyte subsets at d 90 (D90) post-allo-HSCT in 130 children diagnosed with R/R-AML between September 2019 and October 2022 at the Children's Hospital of Soochow University. Lymphocyte subgroups were assessed by flow cytometric analysis on D90 and compared among human leukocyte antigen (HLA)-matched sibling donor HSCT (MSD) (n = 14), haploidentical donor HSCT (n = 94), and HLA-matched unrelated donor HSCT (n = 22) groups. The associations between the counts and frequencies of lymphocyte subgroups and prognosis were assessed. RESULTS: In the MSD group, CD4+ T cell frequency and count were the highest (P < 0.001). Among the examined lymphocyte subsets, a lower proportion of CD4+ T cells (<14.535 %) at D90 correlated with a higher risk of cytomegalovirus infection (P = 0.002). A higher CD4+ T cell count (>121.39/µL) at D90 after HSCT was the single predictor of a lower fatality risk across all lymphocyte subgroups (univariate: P = 0.038 cut-off: 121.39/µL; multivariate: P = 0.036). No association with relapse was observed. CONCLUSIONS: CD4+ T cell count may be used to identify pediatric patients with R/R-AML with a greater mortality risk early after HSCT.

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BACKGROUND: Early and precise diagnosis of bronchopulmonary dysplasia (BPD) is essential to improve the prognosis of preterm infants with BPD. Studying ferroptosis-related genes for diagnostic markers of BPD was the objective of this study. METHODS: Using the GEO database and the FerrDb database, we obtained the GSE32472 dataset and screened the ferroptosis-related differentially expressed mRNAs (FRDE-mRNAs). By using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), possible biological functions and pathways were identified for FRDE-mRNAs. Three machine learning algorithms (LASSO, SVM-RFE, Random Forest) were used to recognize hub genes, as well as CIBERSORT for exploring the immune landscape of BPD and controls. Functional predictions for hub genes were made using single-gene gene set enrichment analysis (GSEA). RESULTS: Twenty three FRDE-mRNAs were obtained and were mainly involved in autophagy, fatty acid metabolism and ferroptosis. The four hub genes (LPIN1, ACADSB, WIPI1 and SLC7A11) screened were utilized to construct a diagnostic nomogram. The receiver operating characteristic (ROC) curves and calibration curves demonstrateld that the nomogram exhibited good predictive performance. Eight types of immune cell markers differed significantly between BPD and controls. CONCLUSION: We developed a diagnostic model for BPD, which could facilitate the early diagnosis and timely intervention of BPD. IMPACT: The role of ferroptosis in bronchopulmonary dysplasia is rarely reported. The ferroptosis-related genes (LPIN1, ACADSB, WIPI1 and SLC7A11) we identified could serve as early diagnostic biomarkers for BPD. Immune cell infiltration features in BPD and signaling pathways associated with marker genes give new insight into the disease process and provide a basis for further research.

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This study aimed to investigate the effects of dietary supplementation of underfed Hu ewes from d 35 to 110 of gestation with either rumen-protected L-arginine (RP-Arg) or N-carbamylglutamate (NCG) on placental amino acid (AA) transport, angiogenic gene expression, and steroid anabolism. On d 35 of gestation, 32 Hu ewes carrying twin fetuses were randomly divided into four treatment groups, each consisting of eight ewes, and were fed the following diets: A diet providing 100% of NRC's nutrient requirements for pregnant ewes (CON); A diet providing 50% of NRC's nutrient requirements for pregnant ewes (RES); RES diet plus 5 g/d NCG (RES + NCG); or RES diet plus 20 g/d RP-Arg (RES + ARG). On the d 110 of pregnancy, blood samples were taken from the mother, and samples were collected from type A cotyledons (COT; the fetal portions of the placenta). The levels of 17ß-estradiol and progesterone in the maternal serum and both the capillary area density (CAD) and capillary surface density (CSD) in type A COT were decreased in response to Arg or NCG supplementation when compared to the RES group. The concentrations of arginine, leucine, putrescine and spermidine in type A COT were higher (P < 0.05) in the RES + ARG or RES + NCG group than in the RES group. The mRNA expression levels of inducible nitric oxide synthase (iNOS) and solute carrier family 15, member 1 (SLC15A1) were increased (P < 0.05) while those of progesterone receptor (PGR) and fibroblast growth factor 2 (FGF2) were decreased in type A COT by supplementation with either NCG or RP-Arg compared to the RES group. The results suggest that providing underfed pregnant ewes from d 35 to 110 of gestation with a diet supplemented with NCG or RP-Arg improves placental AA transport, and reduces the expression of angiogenic growth factor genes and steroid anabolism, leading to better fetal development.

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BACKGROUND: An assessment of functional gastrointestinal disorders (FGIDs) in premature infants in their first year of life and neonatal factors influencing the progression of FGIDs was conducted in this research. METHODS: Subjects selected for the retrospective study involved preterm infants being hospitalized in the neonatal department of Northern Jiangsu People`s Hospital from September 2018 to September 2021. Data on neonatal risk factors such as gestational age, gender, birth weight, mode of delivery, feeding pattern, antibiotic administration and addition of probiotics, duration of hospitalization, maternal history of smoking, and mental health status, were all collected and analyzed. FGIDs were diagnosed according to Rome IV criteria. RESULTS: This study included 988 preterm infants, with 725 (73.4%) having at least one FGID, 449 (45.4%) with infant colic, 411 (41.6%) with infant regurgitation, 237 (24.0%) with infant dyschezia, 190 (19.2%) with functional constipation, and 34 (3.4%) with functional diarrhea throughout the first year of life. In total, 263 infants (26.6%) without FGID symptoms were included in the control group. Further, a higher prevalence of FGIDs was observed in preterm infants with infant colic as well as infant regurgitation in particular as being characterized by a low gestational age ( < 32 w), low birth weight ( < 1.5 kg), Cesarean section, formula feeding, neonatal antibiotics use, hospitalization longer than 7 days, and maternal history of smoking. It was found from association analyses that infants exclusively breastfed in their first month of life were at lower risk for regurgitation than those in the control group. CONCLUSIONS: Unnecessary antibiotic use in the neonatal period, Cesarean delivery, passive smoking, lack of breastfeeding along with inappropriate probiotics usage are major risk factors for FGIDs, and their systematic control may be effective in reducing the susceptibility to and prevalence of FGIDs in preterm infants in the first year of life.

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OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

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OBJECTIVE: To investigate the relationship between the nutrition status of infants with bronchopulmonary dysplasia (BPD) at the first 4 weeks of life and the likelihood of developing neonatal malnutrition. METHODS: A total of 1064 infants were divided into a BPD group and a non-BPD group. After propensity score matching, there were 282 infants in each group. Infants were further divided into a neonatal malnutrition （NM） group and a well-nourished （WN） group. Clinical factors, nutrition intake, and growth parameters were collected and analyzed. Multivariate logistic regression model was used to determine the factors associated with neonatal malnutrition. RESULTS: 1. Compared with infants in the non-BPD group, the infants in BPD group had more fluid intake and lower calorie and protein intake after the second week, longer invasive ventilation time, and longer time to total oral feeding and parenteral nutrition (PN), and the difference was more significant in NM infants than in WN infants (P < 0.05). 2. The weight/length, body mass index, triponderal mass index, and weight gain velocity in the BPD group were significantly lower than in the non-BPD group (P < 0.05) and lower in NM infants than in WN ones (P < 0.05). 3. Multivariable system regression analysis showed that invasive ventilation time, lipid intake in week 4, time to reach full feeding, and duration of PN were independent risk factors for NM. CONCLUSION: Enhancing calorie and macronutrient intake, reducing invasive ventilation, and achieving full gastrointestinal feeding early may be effective measures to avoid malnutrition in infants with BPD.

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OBJECTIVE: To study the clinical value of serum neuroglobin in evaluating hypoglycemic brain injury in neonates. METHODS: A total of 100 neonates with hypoglycemia were enrolled as subjects. According to amplitude-integrated EEG (aEEG) findings and/or clinical manifestations, they were divided into symptomatic hypoglycemic brain injury group (n=22), asymptomatic hypoglycemic brain injury group (n=37) and hypoglycemic non-brain injury group (n=41). The three groups were compared in terms of blood glucose, duration of hypoglycemia, levels of neuroglobin and neuron-specific enolase (NSE), and modified aEEG score. The correlation of neuroglobin with NSE and modified aEEG score was analyzed. The receiver operating characteristic (ROC) curve was plotted. RESULTS: Compared with the asymptomatic hypoglycemic brain injury and hypoglycemic non-brain injury groups, the symptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Compared with the hypoglycemic non-brain injury group, the asymptomatic hypoglycemic brain injury group had significantly lower blood glucose and modified aEEG score, significantly higher neuroglobin and NSE levels, and a significantly longer duration of hypoglycemia (P<0.05). Neuroglobin was positively correlated with NSE and duration of hypoglycemia (r=0.922 and 0.929 respectively; P<0.05) and negatively correlated with blood glucose and modified aEEG score (r=-0.849 and -0.968 respectively; P<0.05). The areas under the ROC curve of neuroglobin, NSE and modified aEEG score were 0.894, 0.890 and 0.941 respectively, and neuroglobin had a sensitivity of 80.8% and a specificity of 95.8% at the optimal cut-off value of 108 mg/L. CONCLUSIONS: Like NSE and modified aEEG score, serum neuroglobin can also be used as a specific indicator for the assessment of brain injury in neonates with hypoglycemia and has a certain value in clinical practice.

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OBJECTIVE: To investigate the relationship between blood glucose fluctuation and brain damage in the hypoglycemia neonates. STUDY DESIGN: A retrospective study including all neonates hospitalized due to hypoglycemia from September 2013 to August 2016 was performed. All the 58 hypoglycemia infants were divided into two groups-the brain-damaged group and the nonbrain-damaged group, according to head magnetic resonance imaging and/or amplitude-integrated electroencephalogram. Relationship between glucose variability and brain damage and whether these variation indexes could act as early indicators for hypoglycemic brain damage were investigated. RESULTS: Of the 13 brain-damaged cases, the lowest blood glucose (LBG) level was lower, while duration of hypoglycemia was longer compared with the 45 nonbrain-damaged cases (p < 0.001). The largest amplitude of glycemic excursions, standard deviation of blood glucose, and mean amplitude of glycemic excursions (MAGE) of the brain-damaged group were higher (p < 0.001). Under receiver-operating characteristic curve, values of area under the curve of MAGE were 0.892, duration of hypoglycemia was 0.921, and LBG was 0.109 (p < 0.0001). CONCLUSION: Brain damage of the hypoglycemia neonates relates not only with LBG and duration of hypoglycemia but also with the blood glucose variation indexes; MAGE and duration of hypoglycemia could act as predictors for brain damage.

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