Circular RNAs expression profiles and bioinformatics analysis in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) has long been considered the most challenging chronic lung disease for neonatologists and researchers due to its complex pathological mechanisms and difficulty in prediction. Growing evidence indicates that BPD is associated with the dysregulation of circular RNAs (circRNAs). Therefore, we aimed to explore the expression profiles of circRNAs and investigate the underlying molecular network associated with BPD. METHODS: Peripheral blood was collected from very-low-birth-weight (VLBW) infants at 5-8 days of life to extract PBMCs. Microarray analysis and qRT-PCR tests were performed to determine the differentially expressed circRNAs (DEcircRNAs) between BPD and non-BPD VLBW infants. Simultaneous analysis of GSE32472 was conducted to obtain differentially expressed mRNAs (DEmRNA) from BPD infants. The miRNAs were predicted by DEcircRNAs and DEmRNAs of upregulated, respectively, and then screened for overlapping ones. GO and KEGG analysis was performed following construction of the competing endogenous RNA regulatory network (ceRNA) for further investigation. RESULTS: A total of 65 circRNAs (52 upregulated and 13 downregulated) were identified as DEcircRNAs between the two groups (FC >2.0 and p.adj <0.05). As a result, the ceRNA network was constructed based on three upregulated DEcircRNAs validated by qRT-PCR (hsa_circ_0007054, hsa_circ_0057950, and hsa_circ_0120151). Bioinformatics analysis indicated these DEcircRNAs participated in response to stimulus, IL-1 receptor activation, neutrophil activation, and metabolic pathways. CONCLUSIONS: In VLBW infants with a high risk for developing BPD, the circRNA expression profiles in PBMCs were significantly altered in the early post-birth period, suggesting immune dysregulation caused by infection and inflammatory response already existed.

Neonatal Glanzmann thrombasthenia: a case report and literature review / 中国新生儿科杂志

Objective:To study the clinical features and genotypes of neonatal Glanzmann thrombasthenia(NGT).Methods:A male neonate with NGT admitted to the Department of Neonatology of our hospital was retrospectively reviewed. CNKI, Wangfang database, VIP, the Chinese Medical Journal Full Text database, PubMed and Embase database were searched using key words '(neonate OR newborn) AND (Glanzmann thrombasthenia)' both in English and Chinese. The clinical features and genotypes of NGT were summarized and analyzed.Results:A male full-term neonate was admitted to our hospital for mass on the forehead and ecchymosis and petechiae on the body within half an hour after birth. He gradually developed subgaleal hemorrhage and severe anemia. Platelet count, mean platelet volume and coagulation functions were normal. The platelet aggregation test indicated decreased platelet aggregation rate induced by arachidonic acid and adenosine diphosphate. Genetic testing revealed two heterozygous mutations in the patient's ITGA2B gene: NM_000419.4: c.886G>A(p.Gly296Arg) and NM_000419.4: c.2855dup(p.Phe953Valfs*83). A total of 42 literature involving 44 patients (our case included) with NGT were retrieved. 33 cases (75.0%) of NGT showed ecchymosis or petechiae on the first day after birth. For 13 cases with detailed information, 5 cases with severe anemia were given erythrocyte and plasma transfusion and platelet transfusion was given in 1 case. 4 cases had homozygous variants and 4 cases showed compound heterozygous variants. 10 cases had follow-up records, including 2 cases without any bleeding and 8 cases with varying degrees of bleeding during follow-up. No deaths were reported.Conclusions:Neonates with ecchymosis and petechiae in the early postnatal period should be suspected of NGT. Blood transfusion is preferred when the indication for transfusion is met.

Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study / 中华医学杂志(英文版)

BACKGROUND@#Antenatal corticosteroids (ACS) can significantly improve the outcomes of preterm infants. This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units (NICU) and to explore perinatal factors associated with ACS use, using the largest contemporary cohort of very preterm infants in China.@*METHODS@#This cross-sectional study enrolled all infants born at 24 +0 to 31 +6 weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st, 2019 to December 30th, 2019. The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery. Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage.@*RESULTS@#A total of 7828 infants were enrolled, among which 6103 (78.0%) infants received ACS. ACS use rates increased with increasing gestational age (GA), from 177/259 (68.3%) at 24 to 25 weeks' gestation to 3120/3960 (78.8%) at 30 to 31 weeks' gestation. Among infants exposed to ACS, 2999 of 6103 (49.1%) infants received a single complete course, and 33.4% (2039/6103) infants received a partial course. ACS use rates varied from 30.2% to 100% among different hospitals. Multivariate regression showed that increasing GA, born in hospital (inborn), increasing maternal age, maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS.@*CONCLUSIONS@#The use rate of ACS remained low for infants at 24 to 31 weeks' gestation admitted to Chinese NICUs, with fewer infants receiving a complete course. The use rates varied significantly among different hospitals. Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.

A study on the changes and clinical value of plasma RIP3 levels in neonatal late-onset sepsis / 中国新生儿科杂志

Objective:To study the changes of plasma receptor interacting protein 3 (RIP3) levels in neonatal late-onset sepsis (LOS) and to determine its clinical value.Methods:From October 2019 to April 2021, plasma samples and clinical data of LOS infants admitted to our hospital were prospectively studied. Infants with similar gestational ages admitted for non-infectious diseases were assigned into the control group. Enzyme-linked immunoassay was used to determine plasma RIP3 levels. The clinical value of plasma RIP3 in the diagnosis and treatment of neonatal LOS were analyzed.Results:A total of 152 cases (76 in the LOS group and 76 in the control group) were included in the study. No significant differences existed in the baseline data between the two groups. A total of 226 plasma samples were collected (76 samples from the LOS group before treatment, 74 samples after treatment and 76 samples from the control group). The plasma RIP3 level of LOS group before treatment (19.9±6.3 ng/ml) was significantly higher than the control group (11.4±3.5 ng/ml) and the after treatment group (11.9±3.5 ng/ml) ( P<0.05). The plasma RIP3 level had good diagnostic value for neonatal LOS (AUC=0.884). With cut-off value of 15.5 ng/ml, the plasma RIP3 showed the best diagnostic efficacy (Youden index 0.658, sensitivity 72.4%, specificity 93.4%, positive likelihood ratio 11.0, negative likelihood ratio 0.3). Conclusions:Plasma RIP3 level is closely related with neonatal LOS and may be used for the early diagnosis and therapeutic evaluation of neonatal LOS.

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.

Efficacy of sequential heated humidified high flow nasal cannula after extubation in premature infants with pulmonary hemorrhage / 中华实用儿科临床杂志

Objective@#To investigate the clinical efficacy of sequential heated humidified high flow nasal ca-nnula(HHHFNC)after extubation in premature infants with pulmonary hemorrhage.@*Methods@#A total of 52 premature infants with pulmonary hemorrhage were selected, who were randomly (by means of random number table) given nasal intermittent positive pressure ventilation(NIPPV)(27 cases) and HHHFNC (25 cases) as a sequential respiratory su-pport from January 2017 to January 2018 at Suzhou Hospital of Nanjing Medical University were selected.The incidence of the basic conditions of the 2 groups of premature infants [gestational age, birth weight, mechanical ventilation days after pulmonary hemorrhage, high-frequency ventilation, usage of nitric oxide(NO)], blood gas analysis indicators at 1 h before extubation and ventilator parameters including the arterial oxygen partial pressure [pa(O2)], arterial partial pressure of carbon dioxide [pa(CO2)], pH value, positive end-expiratory pressure(PEEP), respiratory rates (RR), peak inspiratory pressure (PIP), fraction of inspiration oxygen (FiO2) were compared.The blood gas analysis after extubation [pa(O2), pa(CO2), pH value] at 1 h, outcome events/complications at the end of treatment (reintubation, uration of oxygen therapy after pulmonary hemorrhage, hospitalization days, bronchial pulmonary hypoplasia, ventilator associated pneumonia, feeding intolerance, neonatal necrotizing enterocolitis, pneumothorax) were also compared.@*Results@#There were no significant differences between the NIPPV group and the HHHFNC group in the following items: gestational age, birth weight, mechanical ventilation days after pulmonary hemorrhage, high-frequency ventilation, usage of NO[(30.5±2.9) weeks vs.(31.6±2.7) weeks, 1 325(818) g vs.1 400(800) g, 5 days vs.4 days, 25.9%(7/27 cases) vs.24.0%(6/25 cases), 7.4%(2/27 cases)vs.0(0/25 cases), all P>0.05]. There were no significant differences between the two groups in blood gas analysis indicators before extubation at 1 h and ventilator parameters [pa(O2), pa(CO2), pH value, PEEP, RR, PIP, FiO2], blood gas analysis [pa(O2), pa(CO2), pH value] after extubation at 1 h (all P>0.05); There were no significant differences between the two groups in reintubation, hospitalization days, bronchial pulmonary hypoplasia, ventilator associated pneumonia, feeding intolerance, neonatal necrotizing enterocolitis, pneumothorax [7.4%(2/27 cases) vs.4.0%(1/25 cases), 43(29) days vs.41(22) days, 40.7%(11/27 cases ) vs.16.0%(4/25 cases), 11.1%(3/27 cases) vs.12.0%(3/25 cases), 37.0%(10/27 cases) vs.32.0%(8/25 cases), 7.4%(2/27 cases ) vs.12.0%(3/25 cases), 7.4%(2/27 cases) vs.12.0%(3/25 cases)] (all P>0.05). The duration of oxygen therapy after pulmonary hemorrhage in the HHHFNC group was shorter than that in the NIPPV group [25(30) days vs.9(22) days, P<0.05].@*Conclusions@#As a sequential respiratory support for preterm infants with pulmonary hemorrhage, HHHFNC has shorter duration of oxygen therapy after pulmonary hemorrhage than that of NIPPV, suggesting that HHHFNC is an ideal non-invasive ventilation treatment.

One case report of autoantibody-associated congenital heart block / 临床儿科杂志

ObjectiveTo explore the pathogenesis, clinical manifestations, diagnosis, and treatment of autoanti-body-associated congenital heart block.MethodsThe clinical data of one child with autoantibody-associated congenital heart block was retrospectively analyzed.ResultsIn 24 week gestation, fetal bradycardia had been found by routine fetal echocar-diography. After birth, the anti-SSA/Ro antibodies and anti-SSB/La antibodies were positive in both infant and her mother. The diagnosis of autoantibody-associated congenital heart block was conifrmed. Intravenous immunoglobulin at 1 g/kg was adminis-trated. At 6 months follow-up, the electrocardiogram suggested type I second degree atrioventricular block.ConclusionIn the fetus or neonates found to have bradycardia and excluded the cardiac structural abnormalities, the autoimmune antibody should been tested and early intervention should been promoted.

Effect of humidified high flow nasal cannula on severe apnea in preterm infants / 中国小儿急救医学

Objective To investigate the effect of humidified high flow nasal cannula (HHFNC) on severe apnea in preterm infants.Methods Eighty-two preterm infants who developed apnea more than twice in short time,recurred within 6 hours or needed mask respirator were divided into HHFNC group(n =40) and nasal continuous positive airway pressure(NCPAP) group (n =42).Both groups were given aminophylline intravenously.The total therapeutic effect rate,the number of cases who needed mechanical ventilation during the observation period,the duration of non-invasive ventilation,the duration of oxygen therapy,the oxygen exchange indexes and the complications of two groups were observed.Results There were no significant differences between two groups in the therapeutic effect rate,the number of cases who need invasive ventilation,the duration of non-invasive ventilation time,oxygen exchange indexes and the duration of oxygen usage (P ＞ 0.05).The numbers of nose injury of HHFNC group were less than those of the NCPAP group [10.0％ (4/40) vs.30.9％ (13/42)] (P ＜0.05).No significant differences were found between two groups in the complication of necrotizing enterocolitis or feeding intolerance,respiratory infection,retinopathy of prematurity,bronchopulmonary dysplasia (P ＜ 0.05).Conclusion HHFNC has the same effect as NCPAP in the treatment of severe apnea in preterm infants except for lower prevalence of nose injury.

Effects of exogenous melatonin on plasma corticosterone and adrenal glucocorticoid receptor mRNA in neonatal rats / 临床儿科杂志

Objective To study the effects of exogenous melatonin on plasma corticosterone(CS)and adrenal glucocorticoid receptor(GR)mRNA in neonatal rats after hypoxic-ischemic brain damage(HIBD). Methods One hundred and forteen 7-day-old Sprague-Dawley rats were randomly divided into four groups:model group(K group),sham operation group(H group),melatonin-treated group(T group),and normal control group(S group). Blood was obtained in different time points after HIBD. Plasma CS levels were measured by radioimmunoassay(RIA). The expression of GR mRNA was detected by semi-quantitative reverse transcriptase polymerase chain reaction(RT-PCR). Results Plasma level of CS increased and the expression of GR mRNA decreased significantly after HIBD,however,these changes were markedly reversed by exogenous melatonin. Conclusions Plasma CS and adrenal gland GR were involved in the pathological process of HIBD. Exogenous melatonin could up-regulate the expression of GR by decreasing the level of endogenous CS,so it may alleviate the excess stress injury after HIBD.