[Clinical application of whole exome sequencing in monogenic hereditary disorders in critically ill newborns].

OBJECTIVE: To explore the value and significance of the clinical application of whole exome sequencing (WES) in monogenic hereditary disorders in critically ill newborns. METHODS: The critically ill newborns in the neonatal intensive care unit with suspected hereditary diseases or unclear clinical diagnosis from June 2016 to December 2018 were enrolled. The whole blood samples from both newborns and parents were collected for WES. The detected genetic mutations were classified, the mutations associated with clinical phenotypes were searched for, and Sanger sequencing was performed to verify the mutations. RESULTS: A total of 45 newborns were enrolled, including 22 males and 23 females, and the median age of onset was 2.0 days. Of the 45 newborns, 12 (27%) were confirmed with monogenic hereditary disorders by molecular diagnostics, and the median age at diagnosis was 31.5 days. Of the 12 newborns with monogenic hereditary disorders, 5 (42%) were partially associated with clinical phenotypes but confirmed with monogenic hereditary disorders by additional information supplement and analysis. The improvement rate of newborns with monogenic hereditary disorders was 67% (8/12) after treatment. CONCLUSIONS: WES technology is a powerful tool for finding genetic mutations in monogenic hereditary disorders in critically ill newborns and can play a crucial role in clinical decision-making. However, a comprehensive interpretation of sequence data requires physicians to take the clinical phenotypes and the results of WES into consideration simultaneously.

[A clinical study of growth and metabolism of small for gestational age infants].

OBJECTIVE: To study the differences in growth and metabolism between small for gestational age (SGA) infants and appropriate for gestational age (AGA) infants. METHODS: A total of 1 370 preterm infants were enrolled in this study. According to the association between gestational age and birth weight, they were divided into SGA group with 675 infants and AGA group with 695 infants. The two groups were compared in terms of general conditions, physical growth and blood biochemical parameters. RESULTS: The SGA group had a significantly longer length of hospital stay than the AGA group (P<0.05). Compared with the AGA group, the SGA group had significantly lower body weight, body weight Z score, and body length at discharge and significantly higher incidence rate of extrauterine growth retardation and growth rate of head circumference (P<0.05). Compared with the AGA group, the SGA group had significantly longer time to full enteral nutrition and duration of parenteral nutrition (P<0.05). Compared with the AGA group, the SGA group had significantly higher levels of albumin, prealbumin, and serum phosphorus on admission and total bile acid before discharge, as well as a significantly lower albumin level before discharge (P<0.05). The incidence rates of asphyxia, neonatal respiratory distress syndrome, myocardial damage, feeding intolerance, pneumonia, sepsis, hypoglycemia and hypothyroxinemia in the SGA group were significantly higher than in the AGA group (P<0.05). CONCLUSIONS: Compared with AGA infants, SGA infants have significantly delayed physical development during hospitalization and significantly higher incidence rates of extrauterine growth retardation and related complications.

[Effect of prone positioning on respiratory function in very preterm infants undergoing mechanical ventilation].

OBJECTIVE: To explore the effect of prone positioning on respiratory function in very preterm infants undergoing mechanical ventilation. METHODS: A total of 83 very preterm infants treated with mechanical ventilation were enrolled in the study and were randomly assigned to supine group and prone group. Four infants withdrew from the study and 79 infants completed treatment and observation (37 in the supine group and 42 in the prone group). Infants in both groups were mechanically ventilated in a volume assist-control mode. Infants in the prone group were ventilated in the supine position for 4 hours and in the prone position for 2 hours. Ventilator parameters, arterial blood gas analysis, and vital signs were recorded before grouping, every 6 hours in the supine group, and every hour after conversion into the prone position in the prone group, respectively. RESULTS: Fraction of inspired oxygen (FiO2), peak inspiratory pressure, mean inspiratory pressure, and duration of ventilation were significantly lower in the prone group than in the supine group (P<0.05); there were no significant differences in tidal volume or positive end-expiratory pressure between the two groups (P>0.05). The prone group had a significantly higher PO2/FiO2 ratio but significantly lower oxygenation index and respiratory rate than the supine group (P<0.05). There were no significant differences in arterial oxygen tension, pH, base excess, heart rate, or mean blood pressure between the two groups (P>0.05). CONCLUSIONS: Alternating ventilation between the prone position and supine position can improve oxygenation function, decrease the fraction of inspired oxygen, and shorten the duration of mechanical ventilation in very preterm infants undergoing mechanical ventilation.

Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by targeting the Notch2 oncogene and correlates with good prognosis in patients with glioblastoma multiforme.

Glioblastoma stem-like cells (GSCs) are responsible for the initiation and progression of glioblastoma multiforme (GBM), and microRNAs (miRNAs) play an important role in this disease. However, the mechanisms underlying the role of miRNAs in the stemness of GSCs have not been completely elucidated. We previously showed that miR-181a is downregulated in GBM and may predict prognosis in patients with this disease. Here, we demonstrate that the upregulation of miR-181a suppressed GSC formation and inhibited GBM tumorigenesis by targeting the Notch2 oncogene. We found that miR-181a was downregulated in GSCs derived from human glioblastoma U87MG and U373MG cells. The high expression of miR-181a inhibited the levels of stemness-related markers CD133 and BMI1, attenuated sphere proliferation, promoted cell apoptosis, and reduced the tumorigenicity of GSCs. MiR-181a decreased the expression of Notch2 by targeting the 3'-untranslated region of its mRNA. Notch2 overexpression inhibited the effects of miR-181a downregulation on GSCs, and was negatively correlated with miR-181a expression. Moreover, high Notch2 expression together with low miR-181a expression was correlated with a shorter median overall survival for GBM patients. Together, these data show that miR-181a may play an essential role in GSC formation and GBM progression by targeting Notch2, suggesting that Notch2 and miR-181a have potential prognostic value as tumor biomarkers in GBM patients.

The correlation of microRNA-181a and target genes with poor prognosis of glioblastoma patients.

To investigate the expression and clinical significance of miR-181a and its target genes in glioblastoma multiforme (GBM), the expression levels of miR-181a and three target genes in human normal brain tissues and GBM were analyzed in silico using gene microarray, gene ontology, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results show that miR-181a is down-regulated in GBM patients. The three target genes, ANGPT2, ARHGAP18 and LAMC1, are negatively correlated with the expression of miR-181a. Moreover, high expression of ANGPT2 or LAMC1 together with large size of GBM is correlated with a shorter median overall survival. In conclusion, our results showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients.

[Nutrition status of premature infants in the neonatal intensive care unit and risk factors of extrauterine growth retardation].

OBJECTIVE: To study the nutrition status of premature infants in the neonatal intensive care unit (NICU) and risk factors of extrauterine growth retardation (EUGR). METHODS: The clinical data of 110 premature infants who were admitted to the NICU from August 2007 to September 2008 were retrospectively reviewed. The possible factors influencing the nutrition status were analyzed. RESULTS: The incidence of EUGR was 53.6% (59/110), 31.8% (35/110) and 10.0% (11/110) by weight, length and head circumference respectively among the premature infants. The risk factors of EUGR included: small-for-gestational-age (SGA), low birth weight, low speed of weight gain during hospitalization, large extent of physiological weight loss, long time to reach oral calorie goal, and maternal complications. CONCLUSIONS: The nutrition status and physical development are not desirable in premature infants hospitalized in the NICU. Therefore, reasonable nutritional support and proactive control of risk factors are important strategies to improve the perinatal nutrition and long-term prognosis.

[Effects of triiodothyronine on the learning and memory behaviors in neonatal mice following excitotoxic brain damage].

OBJECTIVE: Some research has shown that learning and memory function impairments in rats with hypothyroidism are associated with triiodothyronine (T3) deficiency in neurons. This study aimed to investigate the effects of L-T3 administration on learning and memory behaviors in neonatal mice with excitotoxic brain damage. METHODS: Seventy-one 5-day-old ICR neonatal mice were randomly assigned to five groups: controls that received intracerebral and intraperitoneal injections of phosphate buffered saline (PBS) (n=14); a group that received intracerebral injections of ibotenic acid (IA) and intraperitoneal injection of PBS (n=14); 3 groups that received intracerebral injections of IA and intraperitoneal injection of L-T3 at 0.2, 0.5, and 1 microg/kg, respectively (n=14-15). Intraperitoneal injections were done 1, 24, 48, 72 and 96 hrs after intracerebral injections. Learning and memory functions were evaluated by the Y-maze discrimination learning test on postnatal days 33-34. RESULTS: The learning and memory functions in the highest L-T3 dose group were significantly better than those in the IA, and the lower L-T3 dose groups, presenting with decreased number of trials to criterion[15.8 + or - 4.5 vs 21.3 + or - 6.3 (IA group), 20.5 + or - 6.0 (0.2 microg/kg L-T3 group) or 21.0 + or - 6.5 (0.5 microg/kg L-T3 group); P<0.05], and achieving a higher correct percentage [91.4+ or - 9.5% vs 79.3 + or - 10.0% (IA group), 77.9 + or - 14.2% (0.2 microg/kg L-T3 group) or 80.7 + or - 12.2% (0.5 microg/kg L-T3 group); P<0.05]. CONCLUSIONS: High-dose L-T3 (1 microg/kg) may improve learning and memory functions in mice following excitotoxic brain damage.

[Neurobehavioral function of neonatal mice following excitotoxic brain damage].

OBJECTIVE: To assess the changes of neurobehavioral function in a neonatal mouse model of excitotoxic brain damage. METHODS: Fifty-five 5-day-old ICR neonatal mice were randomly assigned to three groups: blank (no intravenous) control (n=20), saline control (n=20) and excitotoxic brain damage model (ibotenic acid treatment, n=15). Behavioral function was evaluated by the surface righting reflex test (postnatal days 6-10), the swimming test (postnatal days 8-12) and the Y-maze discrimination learning test (postnatal days 33-34). RESULTS: Righting time in the surface righting reflex test in the ibotenic acid treatment group on postnatal days 6-10 was more prolonged than that in the two control groups (p<0.05). Swimming test scores in the ibotenic acid treatment group were significantly lower than those in the two control groups (p<0.05). In the Y-maze discrimination learning test, the mice from the ibotenic acid treatment group performed significantly worse than two control groups, presenting with increased learning times (19.79+/-2.42 vs 16.29+/-2.48 or 16.30+/-2.37; p<0.05) and achieving a lower correct percentage (86.7% vs 96.5% or 95.0%) (p<0.05). CONCLUSIONS: The developmental reflexes and learning and memory functions were impaired in neonatal mice following excitotoxic brain damage. Behavioral testing is useful in the evaluation of early developmental reflexes and long-term neurobehavioral outcome in neonatal mice with excitotoxic brain damage.