Risk factors for bronchopulmonary dysplasia infants with respiratory score greater than four: a multi-center, prospective, longitudinal cohort study in China.

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity involving both pre- and post-natal factors. A large, prospective, longitudinal cohort study was conducted to determine whether inflammation-related factors are associated with an increased risk of BPD in preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and respiratory score > 4. The study included infants from 25 participating hospitals in China between March 1, 2020 and March 31, 2022. The primary outcomes were BPD and severity of BPD at 36 weeks post-menstrual age. A total of 1362 preterm infants were enrolled in the study. After exclusion criteria, the remaining 1088 infants were included in this analysis, of whom, 588 (54.0%) infants were in the BPD group and 500 (46.0%) were in the non-BPD group. In the BPD III model, the following six factors were identified: birth weight (OR 0.175, 95% CI 0.060-0.512; p = 0.001), surfactant treatment (OR 8.052, 95% CI 2.658-24.399; p < 0.001), mean airway pressure (MAP) ≥ 12 cm H2O (OR 3.338, 95% CI 1.656-6.728; p = 0.001), late-onset sepsis (LOS) (OR 2.911, 95% CI 1.514-5.599; p = 0.001), ventilator-associated pneumonia (VAP) (OR 18.236, 95% CI 4.700-70.756; p < 0.001) and necrotizing enterocolitis (NEC) (OR 2.725, 95% CI 1.182-6.281; p = 0.019). Premature infants remained at high risk of BPD and with regional variation. We found that post-natal inflammation-related risk factors were associated with an increased risk of severe BPD, including LOS, VAP, NEC, MAP ≥ 12 cm H2O and use of surfactant.

Giant omphalocele associated pulmonary hypertension: A retrospective study.

Background: Omphalocele is a common congenital defect of the abdominal wall, management of giant omphalocele (GO) is particularly for pediatric surgeons and neonatologists worldwide. The current study aimed to review and summarize the clinical features and prognosis in neonates with GO complicated with pulmonary hypertension (PH), which is associated with increased mortality, while in hospital. Materials and methods: Medical records of infants with GO between July 2015 and June 2020 were retrospectively analyzed. The patients enrolled were divided into PH and non-PH groups based on the presence or absence of PH, and patients with PH were divided into death and survival groups based on survival status. Clinical characteristics and outcomes were compared between groups, respectively. The risk factors for PH were analyzed by binary logistic regression. Results: In total, 67 neonates were identified as having GO and 24 (35.8%) were complicated with PH. Infants with PH were associated with intubation within 24 h after birth (p = 0.038), pulmonary dysplasia (p = 0.020), presence of patent ductus arteriosus (PDA; p = 0.028), a staged operation (p = 0.002), longer mechanical ventilation days (p < 0.001), oxygen requirement days (p < 0.001), parenteral nutrition (PN) days (p < 0.001), length of neonatal intensive care unit (NICU) or hospital stay (p = 0.001 and 0.002, respectively), and mortality (p = 0.001). The results of multivariable logistic regression analysis revealed that a staged operation was independently associated with PH. In addition, PH patients with lower birth weight, higher peak of pulmonary arterial systolic pressure, and refractory to pulmonary vasodilators (PVD) had increased mortality. Conclusion: Pulmonary hypertension is a serious complication and significantly increases the mortality and morbidities in infants with a GO. In addition, early and serial assessment of PH by echocardiography should be a routine screening scheme, especially in the neonatal omphalocele population who required a staged surgical repair. Clinicians should be aware that infants with PH who had low weight, severe and refractory PH have a higher risk of death.

[Clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight infants].

OBJECTIVE: To study the clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight (ELBW) infants. METHODS: A retrospective analysis was performed for 49 ELBW infants who were admitted from January 1, 2018 to July 30, 2020, with an age of ≤14 days on admission and a duration of parenteral nutrition of > 14 days. According to the type of lipid emulsion received, the ELBW infants were divided into two groups: soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) (n=26) and medium-chain triglycerides/long-chain triglycerides (MCT/LCT) (n=23). The two groups were compared in terms of clinical features, complications, nutrition support therapy, and outcome. RESULTS: The 49 ELBW infants had a mean birth weight of (892±83) g and a mean gestational age of (28.2±2.3) weeks. There was no significant difference between the two groups in the incidence rates of hemodynamically significant patent ductus arteriosus, intraventricular hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia (BPD), grade Ⅲ BPD, sepsis, and pneumonia (P > 0.05). There was also no significant difference in the duration of parenteral nutrition, the age of total enteral nutrition, and head circumference/body length/body weight at discharge between the two groups (P > 0.05). Of all the infants, 22 (45%) had parenteral nutrition-associated cholestasis (PNAC), with 13 (50%) in the SMOF group and 9 (39%) in the MCT/LCT group but there was no significant difference in the incidence of PNAC between the two groups (P > 0.05); however, the infants with PNAC in the SMOF group had significantly lower peak values of direct bilirubin and alanine aminotransferase than those in the MCT/LCT group (P < 0.05). CONCLUSIONS: The application of multi-oil fat emulsion in ELBW infants does not reduce the incidence rate of complications, but compared with MCT/LCT emulsion, SMOF can reduce the severity of PNAC in ELBW infants.

[Application of vacuum stretcher combined with feeding in cranial magnetic resonance imaging examination for neonates: a prospective randomized controlled study].

OBJECTIVE: To study the effect and safety of vacuum stretcher combined with feeding in cranial magnetic resonance imaging (MRI) examination for neonates. METHODS: A prospective study was performed for the neonates with hyperbilirubinemia, with a gestational age of >34 weeks and stable vital signs, who needed cranial MRI examination and did not need oxygen inhalation hospitalized in the Department of Neonatology, Children's Hospital of Zhejiang University School of Medicine, from September to November, 2019. The neonates were randomly divided into a vacuum stretcher combined with feeding group and a conventional sedation group. Vital signs were monitored before, during, and after MRI examination. The success rate of MRI procedure was recorded. RESULTS: A total of 80 neonates were enrolled in the study, with 40 neonates in the vacuum stretcher combined with feeding group and 40 in the conventional sedation group. The vacuum stretcher combined with feeding group had a significantly higher success rate of MRI procedure than the conventional sedation group (P<0.05). As for the neonates who underwent successful MRI examination, the fastest heart rate after examination in the vacuum stretcher combined with feeding group was significantly lower than that in the conventional sedation group (P<0.05), while there were no significant differences between the two groups in transcutaneous oxygen saturation, respiratory rate, and body temperature before and after MRI examination (P>0.05). No complications, such as apnea, acute allergic reactions, and malignant fever, were observed. CONCLUSIONS: Vacuum stretcher combined with feeding can improve the success rate of MRI procedure and reduce the use of sedatives, and meanwhile, it does not increase related risks.

Relationships of Cadmium, Lead, and Mercury Levels With Albuminuria in US Adults: Results From the National Health and Nutrition Examination Survey Database, 2009-2012.

In this cross-sectional study, we evaluated associations between cadmium, lead, and mercury levels and the presence of albuminuria in US adults who participated in the National Health and Nutrition Examination Survey during the period 2009-2012. A total of 2,926 adults aged ≥20 years were included, representing a population-based sample of 18,264,307 persons. Data on blood and urinary levels of cadmium, lead, and mercury and urinary albumin concentration (albuminuria, measured as albumin:creatinine ratio (ACR) ≥30 mg/g) were obtained. Multivariate linear regression was used to analyze associations between log-transformed cadmium, lead, and mercury levels and the presence of albuminuria. Urinary ACR was significantly higher among participants with a blood cadmium level of 0.349-0.692 µg/L (quartile 3) than in those with a blood cadmium level less than or equal to 0.243 µg/L (quartile 1) (crude ß = 0.15, 95% confidence interval (CI): 0.01, 0.28). Participants with a urinary cadmium level greater than or equal to 0.220 µg/L had a significantly higher ACR (0.220-0.403 µg/L (quartile 3): crude ß = 0.12 (95% CI: 0.03, 0.21); ≥0.404 µg/L (quartile 4): crude ß = 0.29 (95% CI: 0.18, 0.39)) than those with a urinary cadmium level less than or equal to 0.126 µg/L (quartile 1). In conclusion, only blood and urinary cadmium levels, not mercury or lead levels, were associated with albuminuria among adults in this population.

[Long-term prognosis of neonates with necrotizing enterocolitis].

OBJECTIVE: To investigate the long-term prognosis of neonates with necrotizing enterocolitis (NEC). METHODS: A total of 83 preterm infants with NEC who survived and were discharged between December 2014 and September 2016 were enrolled and divided into surgery group (n=57) and non-surgery group (n=26). There were 0, 33 and 24 cases of stage I, II and III NEC respectively in the surgery group and 7, 19 and 0 cases respectively in the non-surgery group. The physical development and neurodevelopmental outcomes of the infants were followed up after discharge. RESULTS: Of the 83 infants, the mean corrected age at the end of follow-up was 21±6 months. Of the 83 infants, 31 (37%) had subnormal body weight, and the surgery group had a higher rate of subnormal body weight than the non-surgery group (P<0.05). Twenty-two infants (27%) had subnormal body length and 14 children (17%) had subnormal head circumference among the 83 infants. Eighteen infants (22%) had motor developmental delay/developmental disorders, and the surgery group had a higher incidence rate of the disorders than the non-surgery group (28% vs 8%; P<0.05). Five infants (6%) were diagnosed with cerebral palsy, among whom 4 were in the surgery group and 1 was in the non-surgery group. CONCLUSIONS: Long-term physical development and neurodevelopmental outcomes may be adversely affected in neonates with NEC, in particular in those with severe conditions who need surgical treatment, suggesting that long-term follow-up should be performed for neonates with NEC.

[Clinical features and prognosis of bronchopulmonary dysplasia complicated by pulmonary hypertension in preterm infants].

OBJECTIVE: To study the clinical features and prognosis of bronchopulmonary dysplasia (BPD) complicated by pulmonary hypertension (PH) in preterm infants. METHODS: A retrospective analysis was performed on the clinical data of 191 preterm infants with BPD. RESULTS: In the 191 preterm infants with BPD, 37 (19.4%), all with moderate or severe BPD, developed PH beyond 36 weeks' corrected age. The incidence rates of PH in infants with moderate and severe BPD were 5.7% (5/87) and 47.8% (32/67) respectively. Gestational age and birth weight were lower in infants with PH than in those without PH (P<0.01). Infants with PH had higher incidence rates of small for gestational age (SGA), severe BPD, surgical ligation of patent ductus arteriosus (PDA), neonatal respiratory distress syndrome, hemodynamically significant PDA, and pneumonia than those without PH (P<0.01). Durations of oxygen therapy, intubation, and positive pressure ventilation were longer in infants with PH than in those without PH (P<0.01). Infants with PH had higher incidence rates of retinopathy of prematurity and extrauterine growth retardation, a higher mortality, and a longer length of hospital stay compared with those without PH (P<0.01). In the 37 infants with PH (6 with mild PH, 14 with moderate PH, and 17 with severe PH), those with mild or moderate PH all survived; 15(88%) out of 17 infants with severe PH died. CONCLUSIONS: The incidence of PH is high in preterm infants with moderate or severe BPD. Regular screening of pulmonary artery pressure is recommended for infants with BPD. Infants with low gestational age and birth weight, SGA, and severe BPD are more likely to develop PH. Infants with BPD complicated by PH have relatively high incidence rates of complications, high mortality, and poor prognosis.

Airway administration of corticosteroids for prevention of bronchopulmonary dysplasia in premature infants: a meta-analysis with trial sequential analysis.

BACKGROUND: Uncertainly prevails with regard to the use of inhalation or instillation steroids to prevent bronchopulmonary dysplasia in preterm infants. The meta-analysis with sequential analysis was designed to evaluate the efficacy and safety of airway administration (inhalation or instillation) of corticosteroids for preventing bronchopulmonary dysplasia (BPD) in premature infants. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions to February 2017. All published randomized controlled trials (RCTs) evaluating the effect of airway administration of corticosteroids (AACs) vs placebo or systemic corticosteroid in prematurity were included. All meta-analyses were performed using Review Manager 5.3. RESULTS: Twenty five RCTs retrieved (n = 3249) were eligible for further analysis. Meta-analysis and trial sequential analysis corrected the 95% confidence intervals estimated a lower risk of the primary outcome of BPD (relative risk 0.71, adjusted 95% confidence interval 0.57-0.87) and death or BPD (relative risk 0.81, adjusted 95% confidence interval 0.71-0.97) in AACs group than placebo and it is equivalent for preventing BPD than systemic corticosteroids. Moreover, AACs fail to increasing risk of death compared with placebo (relative risk 0.90, adjusted 95% confidence interval 0.40-2.03) or systemic corticosteroids (relative risk 0.81, 95% confidence interval 0.62-1.06). CONCLUSIONS: Our findings suggests that AACs (especially instillation of budesonide using surfactant as a vehicle) are an effective and safe option for preventing BPD in preterm infants. Furthermore, the appropriate dose and duration, inhalation or instillation with surfactant as a vehicle and the long-term safety of airway administration of corticosteroids needs to be assessed in large trials.

MiR-126a-5p is involved in the hypoxia-induced endothelial-to-mesenchymal transition of neonatal pulmonary hypertension.

Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterized by increased medial and adventitial thickness of the lung vasculature. The underlying mechanisms that regulate the cell phenotype alteration during PPHN remodeling are largely unknown. We randomly selected newborn rats that were exposed to hypoxia (10-12%) or room air for 2 weeks and used a microarray to identify the lung tissue microRNAs (miRNAs) involved in PPHN progression. The role of a key miRNA that affects the endothelial-to-mesenchymal transition (EndMT) in primary cultured rat pulmonary microvascular endothelial cells (RPMECs) was investigated. The expression of miR-126a-5p was elevated in the PPHN model according to microarray analysis. The relative expression of miR-126a-5p in RPMECs increased when they were exposed to hypoxia (P<0.05), consistent with the microarray results. Pecam1 expression decreased, whereas alpha-smooth muscle actin (α-SMA) increased in the hypoxic RPMECs. Knockdown of miR-126a-5p in RPMECs followed by treatment with hypoxia for 48 h resulted in a significant increase in the expression of Pecam1 and a reduction in α-SMA expression, with a simultaneous increase in PI3K (p85ß) and phosphorylation of AKT at serine 473 compared with the negative control. Finally, the circulating miR-126a-5p concentration was upregulated in the PPHN model compared with healthy neonates. We concluded that hypoxia changed the cell homeostasis and that miR-126a-5p was upregulated in PPHN, which is partly responsible for hypoxia-induced EndMT. The mechanism underlying the upregulation of miR-126a-5p by hypoxia probably acts through the p85-ß/p-AKT pathway.

Utility of cytokines to predict neonatal sepsis.

BACKGROUND: Sepsis is an important cause of neonatal morbidity and mortality worldwide. Diagnosis and treatment of neonatal sepsis relies on clinical judgment and interpretation of nonspecific laboratory tests. In a prospective cohort, we measured inflammatory cytokines as a potential biomarker for neonatal sepsis. METHODS: Serum inflammatory cytokine levels were evaluated in the early stage of neonatal sepsis and after antimicrobial treatment. Receiver operating characteristic curves assessed the diagnostic value of cytokines. We performed multiple logistic regression analysis to characterize the role of each cytokine independently for infants with culture proven sepsis. RESULTS: C-reactive protein, interleukin (IL)-6, IL-10 and IL-6/IL-10 levels were significantly elevated in neonatal sepsis when compared with the control group and there were 1.4 (95% confidence interval (CI): 1.2-1.5), 4.9 (95% CI: 4.6-5.1), 5.1 (95% CI: 4.5-5.6), and 10.2 (95% CI: 9.2-11.1) fold greater odds, respectively, to predict neonatal sepsis when increased. After effective treatment, median IL-6 (pretreatment value: 263.0 pg/ml and post-treatment value: 7.4 pg/ml) and IL-6/IL-10 levels (pretreatment value: 16.6 and post-treatment value: 1.4) significantly decreased. The areas under the curve for IL-6, IL-10, IL-6/IL-10 and C-reactive protein for differential diagnosis were 0.98, 0.82, 0.90, and 0.88, respectively. CONCLUSION: IL-6 and IL-6/IL-10 outperformed C-reactive protein to diagnose neonatal sepsis. Of the cytokines studied, IL-6 was the most sensitive, whereas IL-6/IL-10 was the most specific predictor of neonatal sepsis.

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study.

BACKGROUND: With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China. METHODS: All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors. RESULTS: A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization. CONCLUSIONS: Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

[Relationship between expression of endothelial nitric oxide synthase and NADPH oxidase in lungs of mice exposed to chronic hypoxia].

OBJECTIVE: To explore the relationship between the expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase (NOX) in the lungs of mice treated by chronic hypoxic exposure. METHODS: Thirty male wild-type (WT) C57Bl/6 mice and thirty male eNOS-knockout (KO) C57BL/6 mice were randomly divided into normoxic groups (exposed to normoxia for 7 days or 21 days), hypoxic groups (exposed to 10% oxygen for 7 days or 21 days), and treatment groups (exposed to 10% oxygen and orally administrated 10 mmol/L 4-hydroxy TEMPO in drinking water for 7 days or 21 days) (n=6 in each group). The remodeling of the small pulmonary arteries was evaluated by the percentage of media wall thickness (MT%). The weight ratio of right ventricle to left ventricle plus septum (RV/[LV+S]) was calculated to evaluate the hypertrophy of right ventricle. Real-time PCR was used to measure the mRNA expression of NOX2, NOX4, and eNOS in mouse lungs. ELISA was used to determine the concentration of reactive oxygen species (ROS) in mouse lungs. RESULTS: In WT mice and KO mice, the hypoxic groups had significantly increased pulmonary vascular remodeling and RV/[LV+S] compared with the normoxic and treatment groups (P<0.05), but there were no significant differences between the normoxic and treatment groups (P>0.05). In WT mice, the hypoxic and treatment groups had significantly lower ROS concentrations than the normoxic group (P<0.05), but there were no significant differences between the hypoxic and treatment groups (P>0.05). In WT mice, the mRNA expression of eNOS, NOX2, and NOX4 was significantly higher in the hypoxic group than in the normoxic group (P<0.05), and 4-hydroxy TEMPO reversed their over-expression. In the normoxic group, the KO mice had significantly higher NOX2 and NOX4 mRNA expression than the WT mice (P<0.05); in KO mice, the hypoxic group showed no significant changes in NOX4 mRNA expression (P>0.05), but had significantly reduced NOX2 mRNA expression (P<0.05), as compared with the normoxic group; the treatment group had reduced expression of NOX2 mRNA expression and increased NOX4 mRNA expression (P<0.05), as compared with the hypoxic group. CONCLUSIONS: eNOS plays a key role in the regulation of expression of NOX2 and NOX4 in the lungs exposed to hypoxia. It suggests that NOX and eNOS may physically interact with one another in pulmonary vascular remodeling induced by chronic hypoxia.

High shear stress-induced pulmonary hypertension alleviated by endothelial progenitor cells independent of autophagy.

BACKGROUND: Pulmonary hypertension (PH) is a progressive disease characterized by lung endothelial cell dysfunction and vascular remodeling. Endothelial progenitor cells (EPCs) have been proved to be a potential therapeutic strategy to treat PH. Autophagy has been found to be protective to hypoxia-induced PH. In this study, we applied high shear stress (HSS)-induced PH, and examined whether EPCs confer resistance against HSS-induced PH through autophagy. METHODS: Pulmonary microvascular endothelial cells (PMVECs) were cultured under HSS with pro-inflammatory factors in an artificial capillary system to mimic the PH condition. Levels of p62, a selective autophagy substrate, were quantified by western blotting. Cell viability was determined by trypan blue exclusion test. RESULTS: The p62 level in PMVECs was increased at 4 hours after HSS, peaked at 12 hours and declined at 24 hours. The cell viability gradually decreased. Compared with PMVECs cultured by empty medium, in cells cultured by EPC-conditioned medium (EPC-CM), the cell viability was significantly higher; however, p62 levels were also significantly higher, suggesting inhibition of autophagy by EPC-CM. Adding choloquine to suppress autophagy decreased the cell viability of PMVECs under PH. CONCLUSIONS: EPC-CM could suppress the autophagic activity of PMVECs in HSS-induced PH. However, suppression of autophagy leads to cell death. EPCs could fight against PH through cellular or molecular pathways independent of autophagy. But it is not proved if induction of autophagy could be a potential strategy to treat HSS-induced PH as hypoxia-induced PH.

[Predicting outcome in necrotizing enterocolitis with the score for neonatal acute physiology: a retrospective study of 62 cases].

OBJECTIVE: To explore the value of the score for neonatal acute physiology (score for neonatal acute physiology, SNAP) in predicting outcome and risk of surgery of necrotizing enterocolitis (NEC). METHOD: A total of 62 NEC patients in neonatal intensive care unit (NICU) of Zhejiang University Children's Hospital were reviewed from October 2001 to October 2011. All the patients were classified into surgery group and non-surgery group according to whether the patient had the surgical intervention. Also the patients were divided into death group and alive group according to the outcome. Data on gestational age at birth, gender, birth weight, early clinical manifestations, treatment and prognosis of all patients were collected. SNAP-II and score for neonatal acute physiology and perinatal extension II (SNAPPE-II) were calculated on the day of diagnosis. RESULT: Abdominal distension, which was seen in 91.9% of the cases, was the commonest early clinical manifestation. The next was residual and bloody stool. SNAP-II and SNAPPE-II score in surgery group (26.5,26.5) were higher than that of the non-surgery group (13.0, 13.0,P = 0.002, 0.006). And the same scores in death group (29.0,32.0) were higher than those in the alive group (8.0, 8.0) (P = 0.000, 0.000). Measuring the scores as a predictor of surgery, the area under ROC curve for SNAP-II was 0.745, and was 0.714 for SNAPPE-II. The area under ROC curve for SNAP-II was 0.916, and was 0.929 for SNAPPE-II.The best positive point of SNAP-II and SNAPPE-II for predicting surgery was 22 and 28. The best positive point of SNAP-II and SNAPPE-II for predicting death was 18.5 and 22. CONCLUSION: The SNAP-II and SNAPPE-II score may be used to predict the prognosis and the risk of surgery in the NEC patients. The scores are also good predictors of mortality in the early period when NEC occurs.

Polymorphism analysis of the ABCA3 gene: association with neonatal respiratory distress syndrome in preterm infants.

BACKGROUND: Previous reports indicated that mutations in the adenosine triphosphate (ATP)-binding cassette transporter A3 (ABCA3) cause fatal respiratory failure in term infants, and common ABCA3 gene polymorphisms have been characterized at the population level in Caucasians. But the role of ABCA3 in relation to respiratory distress syndrome (RDS) in newborns has not been evaluated within a Chinese population. The aim of this study was to analyze eight single-nucleotide polymorphisms (SNPs) of the ABCA3 gene, and to assess the ABCA3 gene as a candidate gene for susceptibility to RDS in newborns. METHODS: Eight SNPs were selected and genotyped in 203 newborns. The data analysis and statistical tests were used for allele frequencies, haplotype and Hardy-Weinberg equilibrium pairwise linkage disequilibrium measures. RESULTS: There was a haplotype association with SNP rs313909 and SNP rs170447, but no haplotype association was observed among the newborns with and without RDS (P > 0.05). The minor allele frequency (G) of the coding SNP (cSNP) rs323043 (P585P) was significantly increased in preterm infants with RDS. CONCLUSION: There is an association between a synonymous cSNP rs323043 and the development of RDS.

Ghrelin ameliorates hypoxia-induced pulmonary hypertension via phospho-GSK3 ß/ß-catenin signaling in neonatal rats.

Effective treatment and/or prevention strategies for neonatal persistent pulmonary hypertension of the newborn (PPHN) have been an important topic in neonatal medicine. However, mechanisms of impaired pulmonary vascular structure in hypoxia-induced PPHN are poorly understood and consequently limit the development of effective treatment. In this study, we aimed to explore the molecular signaling cascades in the lungs of a PPHN animal model and used primary cultured rat pulmonary microvascular endothelial cells to analyze the physiological benefits of ghrelin during the pathogenesis of PPHN. Randomly selected newborn rats were exposed to hypoxia (10-12%) or room air and received daily s.c. injections of ghrelin (150 µg/kg) or saline. After 2 weeks, pulmonary hemodynamics and morphometry were assessed in the rats. Compared with the control, hypoxia increased pulmonary arterial pressure, right ventricle (RV) hypertrophy, and arteriolar wall thickness. Ghrelin treatment reduced both the magnitude of PH and the RV/(left ventricle+septum (Sep)) weight ratio. Ghrelin protected neonatal rats from hypoxia-induced PH via the upregulation of phosphorylation of glycogen synthase kinase 3ß (p-GSK3ß)/ß-catenin signaling and associated with ß-catenin translocation to the nucleus in the presence of growth hormone secretagogue receptor-1a. Our findings suggest that s.c. administration of ghrelin improved PH and attenuated pulmonary vascular remodeling after PPHN. These beneficial effects may be mediated by the regulation of p-GSK3ß/ß-catenin expression. We propose ghrelin as a novel potential therapeutic agent for PPHN.

[Clinical application of tacrolimus with low-dose prednisone in 21 children with steroid-resistant nephrotic syndrome].

OBJECTIVE: To analyze and evaluate the efficacy and safety of tacrolimus and low-dose steroids in the treatment of steroid-resistant nephrotic syndrome in children. METHOD: Twenty-one children with steroid-resistant nephrotic syndrome enrolled from October 2008 to July 2010 into this retrospective longitudinal study received oral tacrolimus treatment, 0.1 to 0.15 mg/kg per day and once every 12 hours, and prednisone 0.2 to 0.75 mg/kg per day simultaneously. During the treatment, the plasma concentration of tacrolimus, urine volume, urine, serum creatinine and liver function were regularly monitored. RESULT: After 1 to 3 months treatment, 14 cases showed complete remission and 7 cases had partial remission. Sixteen patients received renal biopsy, of whom 6 revealed minimal change nephropathy with complete remission in 3 cases, 3 cases had partial remission;4 cases revealed focal segmental glomerulosclerosis with 2 complete remission and 2 partial remission; other 5 children with IgM nephropathy and 1 mesangial proliferative glomerulonephritis achieved complete remission. Within treatment period, 6 patients presented transient adverse reactions, without altering the principle treatment strategy, but only taking the symptomatic treatment. During follow-up, 1 case was lost to follow-up and the remaining 20 cases were followed up from 2 months to 21 months. In 4 patients the disease relapsed within 1st-year follow-up, while at 2nd-year follow-up, 4 cases had (6 times) recurrence. CONCLUSION: Tacrolimus showed a reliable effect in children with steroid-resistant nephrotic syndrome. Less adverse reactions were seen, and most of them could be tolerated. Nevertheless, the patients had a higher relapse rate after 1 to 2 years treatment. Therefore, the long-term effects of tacrolimus for steroid-resistant nephrotic syndrome remains to be further evaluated.

Fetal pulmonary vascular remodeling in a rat model induced by hypoxia and indomethacin.

OBJECTIVE: This study sought to determine the effect of combined treatment of hypoxia plus indomethacin on pulmonary vascular remodeling in fetal rats. METHODS: Hypoxia and indomethacin were used to treat pregnant rats during 19-21 days of gestation. The adventitia, media, and intima of pulmonary arteries from fetal rats were assessed. Western blots were used for determining the abundance of smooth muscle specific alpha-actin protein (α-SMA), elastin, and endothelial nitric oxide synthase (eNOS) in lung tissues. Plasma brain-type natriuretic peptide (BNP) levels, reflecting the increased right ventricular load or pulmonary arterial pressure, were detected. RESULTS: The ratio of left ventricular free wall plus septum to right ventricular weight significantly increased in hypoxia plus indomethacin-treated group. The medial thickness percentage of pulmonary arteries of < 100 µm and ≥100 µm in diameter from hypoxia plus indomethacin-treated group was higher than that from control or single treatment group. Vascular elastin area percentage and immunostaining density of eNOS from the combined-treated group were higher than other groups. The relative abundance of α-SMA, elastin, and eNOS and plasma BNP levels in hypoxia plus indomethacin-treated group also significantly increased compared with other groups. CONCLUSIONS: Hypoxia and indomethacin had synergistic effect on fetal pulmonary vascular remodeling. This rat model induced by combined treatments can mimic human persistent pulmonary hypertension of the newborn.