Risk factors of bronchopulmonary dysplasia in very preterm infants: a national multicenter study / 中国小儿急救医学

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Damage of striatal neurons mediated by NMDA receptors in glutaric aciduria type Ⅰ / 临床儿科杂志

Objective To explore the excitotoxic role of NMDA receptors in striatal neurons in glutaric aciduria type I (GA1). Methods A GA1 cell model was established by lentivirus-mediated shRNA to GCDH and excessive intake of lysine. The expression levels of NMDA receptors were determined by Western blotting. The striatal neurons were preprocessed by MK801(a NMDA receptor antagonist), then infected with lentivirus and cultured in high concentration lysine. Cell viability was measured using MTT. Apoptosis was assessed using Hoechst33342 staining. Results Compared with the control group, the expression of NR2B protein in the experimental group was increased, and there was statistical difference (P<0.001). The differentces in the cell viability and normal nuclear proportion among experimental group, control group, and MK-801 pretreatment group were statistically significant (P<0.01). The cell viability and normal nucleus proportion in experimental group were significantly lower than those in control group while they were significantly higher in MK-801 pretreated group than those in the experiment group but still significantly lower than those in control group (P all <0.05). Conclusion The accumulation of metabolites in GA 1 played a toxic role in striatal neurons through NMDR receptors.

Damage of striatal neurons mediated by NMDA receptors in glutaric aciduria type Ⅰ / 临床儿科杂志

Objective To explore the excitotoxic role of NMDA receptors in striatal neurons in glutaric aciduria type I (GA1). Methods A GA1 cell model was established by lentivirus-mediated shRNA to GCDH and excessive intake of lysine. The expression levels of NMDA receptors were determined by Western blotting. The striatal neurons were preprocessed by MK801(a NMDA receptor antagonist), then infected with lentivirus and cultured in high concentration lysine. Cell viability was measured using MTT. Apoptosis was assessed using Hoechst33342 staining. Results Compared with the control group, the expression of NR2B protein in the experimental group was increased, and there was statistical difference (P<0.001). The differentces in the cell viability and normal nuclear proportion among experimental group, control group, and MK-801 pretreatment group were statistically significant (P<0.01). The cell viability and normal nucleus proportion in experimental group were significantly lower than those in control group while they were significantly higher in MK-801 pretreated group than those in the experiment group but still significantly lower than those in control group (P all <0.05). Conclusion The accumulation of metabolites in GA 1 played a toxic role in striatal neurons through NMDR receptors.

The expressions of insulin receptor substrate in adipocytes during catch-up growth in neonatal rats with intrauterine growth retardation / 临床儿科杂志

Objective To investigate the expressions of insulin receptor substrate-1 (IRS-1) and insulin receptor sub-strate-2 (IRS-2) in adipocytes during catch-up growth in neonatal rats with intrauterine growth restriction (IUGR) and their correlations with the insulin resistance. Methods Sprague-Dawley rats (clean grade) were randomly divided into control group and food-restricted group after fertilization. Food-restricted group were received about 30%of food amount consumed in control group every day through the whole pregnant period to establish IUGR animal model, and were fed increased amount of breast-milk from postnatal day 1 to 21 to establish the period of catch-up growth in IUGR animal model (IUGR-CG). Fasting serum glu-cose, insulin and triglyceride were measured in blood from heart ventricles of 4-week old SD rats and insulin resistance index was calculated. Pre-adipocytes and mature adipocytes were obtained from SD rats at different age (1-week, 3-week, 5-week and 7-week old) and the former were induced to differentiate toward mature adipocytes. The levels of IRS-1, IRS-2 in the two kinds of mature adipocytes were detected by Real-Time PCR and Western blot. Results The expression levels of IRS-1, IRS-2 mRNA in mature adipocytes of IUGR-CG rats were signiifcantly lower than those of IUGR rats at 5-weeks and 7-weeks old (P<0.05) while the ex-pression levels of IRS-1, IRS-2 mRNA in differentiated adipocytes of IUGR-CG rats were signiifcantly lower than those of IUGR rats at 5-weeks old (P<0.05). The expression levels of IRS-1, IRS-2 protein in two kinds of adipocytes (mature and differentiated adipocytes) of IUGR-CG rats were signiifcantly lower than those of IUGR rats from postpartum week 1 through 7 (P<0.05). Conclusions IRS-1 and IRS-2 expression levels are downregulated in adipocytes during catch-up growth of IUGR rats, which may be closely related with insulin resistance.

Influence of Age on the Perioperative Characteristics of Posterior Lumbar Interbody Fusion / 中国康复理论与实践

Objective To investigate the influence of age on the perioperative characteristics of posterior lumbar interbody fusion (PLIF). Methods 129 patients (25~91 years old) with spondylolisthesis, lumbar stenosis and/or disc degeneration/herniation with instability, or unsuccessful results after a failed previous PLIF. They were divided into control group (0.05) between 2 groups. Conclusion Age can not in-crease the rate of perioperative complications of PLIF, and the advanced age should not be surgical contraindication.

Caspase-3 mediates apoptosis of striatal cells in GA I rat model / 华中科技大学学报（医学）（英德文版）

In previous study, glutaric acid (GA) induced apoptosis of primary striatal neuron in vitro. In order to investigate the neurotoxic effects of GA on neonatal rat corpus striatum and the possible mechanism, 34 male pups were randomly assigned to NS group, low dose GA (LGA, 5 μmol GA/g body weight) group and high dose GA (HGA, 10 μmol GA/g body weight) group. These pups were subcutaneously administered with three injections from postnatal day 3 to 22 at 7:30 am, 15:00 pm and 22:30 pm and killed 12 h after the last injection. Microscopic pathology in corpus striatum was evaluated by HE staining. The apoptotic cells were identified by TUNEL staining. The transcript levels of caspase-3, 8, 9, Bax, Bcl-2 were detected by using real-time PCR and the protein levels of procaspase-3 and the active fraction were evaluated by Western blotting. In LGA and HGA groups, ventricle collapse, cortical atrophy by a macroscope and interstitial edema, vacuolations, widened perivascular space of bilateral striatum by a microscope were observed. TUNEL assay revealed that the apoptotic cells were increased in LGA and HGA groups. The transcript of caspase-3 was up-regulated to 2.5 fold, accompanied by the up-regulation of caspase-9, Bax and down-regulation of Bcl-2. The protein levels of procaspase-3 and the active fraction were up-regulated in LGA and HGA groups. The rat model for GA I showed mitochondrial apoptotic pathway may be involved in the GA-induced striatal lesion. Further studies should be taken to investigate the underlying mechanisms.

Progress in pathogenesis of glutaric aciduria type Ⅰ / 国际儿科学杂志

Glutaric aciduria type Ⅰ is an autosomal recessive disorder resulting from glutaryl-CoA dehydrogenase(GCDH) deflciency.Untreated patients commonly present with severe striatal degeneration and extrapyramidal sequelae during encephalopathic crises.GCDH deficiency leads to accumulation of glutaric acid and 3-hydroxyglutaric acid in tissues and body fluids (especially in brain),which are neurotoxic.There is no correlation between residual enzyme activity caused by mutations in GCDH and phenotype.The pathogenesis of glutaric aciduria type Ⅰ is complicated.Previous studies have demonstrated that glutaric and 3-hydroxyglutaric acids are synthesized in central nervous system and trapped because of limiting transport across the blood-brain barrier.The studies on metabolite-mediated neurotoxicity mainly focus on excitotoxicity,impairment of energy metabolism and oxidative stress.In addition,activation of astrocyte,vascular derangements,inflammatory processes may be a synergism of neurotoxicity.