[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

[Antibiotic use in very low birth weight/extremely low birth weight infants in 15 hospitals in Jiangsu Province of China: a multicenter survey]. / 江苏省15家医院极低/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿æŠ—ç”Ÿç´ ä½¿ç”¨çŽ°çŠ¶è°ƒæŸ¥.

OBJECTIVES: To investigate the current status of antibiotic use in very low birth weight/extremely low birth weight infants in Jiangsu Province of China, and to provide a clinical basis for the quality and improvement of antibiotic management in the neonatal intensive care unit (NICU). METHODS: A retrospective analysis was performed on the data on general conditions and antibiotic use in the very low birth weight/extremely low birth weight infants who were admitted to 15 hospitals of Jiangsu Province from January 1, 2019 to December 31, 2020. A questionnaire containing 10 measures to reduce antibiotic use was designed to investigate the implementation of these intervention measures. RESULTS: A total of 1 920 very low birth weight/extremely low birth weight infants were enrolled, among whom 1 846 (96.15%) were treated with antibiotic, and the median antibiotic use rate (AUR) was 50/100 patient-days. The AUR ranged from 24/100 to 100/100 patient-days in the 15 hospitals. After adjustment for the confounding factors including gestational age, birth weight, and neonatal critical score, the Poisson regression analysis showed that there was a significant difference in the adjusted AUR (aAUR) among the hospitals (P<0.01). The investigation results showed that among the 10 measures to reduce antibiotic use, 8 measures were implemented in less than 50% of these hospitals, and the number of intervention measures implemented was negatively correlated with aAUR (rs=-0.564, P=0.029). CONCLUSIONS: There is a high AUR among the very low birth weight/extremely low birth weight infants in the 15 hospitals of Jiangsu Province, with a significant difference among hospitals. The hospitals implementing a relatively few measures to reduce antibiotic use tend to have a high AUR. It is expected to reduce AUR in very low birth weight/extremely low birth weight infants by promoting the quality improvement of antibiotic use management in the NICU.

[Influence of the coronavirus disease 2019 pandemic on maternal breastfeeding for very low birth weight infants]. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žç–«æƒ å¯¹æžä½Žå‡ºç”Ÿä½“é‡å„¿äº²æ¯æ¯ä¹³å–‚å »çš„å½±å“.

OBJECTIVES: To investigate the changes in the rate and volume of mother's own milk (MOM) feeding for very low birth weight infants (VLBWIs) hospitalized during the prevention and control of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective analysis was performed on the medical data of the VLBWIs with a gestational age of <32 weeks who were born and admitted to the Neonatal Intensive Care Unit of Nanjing Maternal and Child Health Hospital from January 2019 to December 2020. The changes in the rate and volume of MOM feeding for VLBWIs during hospitalization were examined. RESULTS: A total of 301 VLBWIs were enrolled. According to the timing of COVID-19 outbreak, these infants were divided into a pre-CIVID-19 group with 205 VLBWIs and a post-COVID-19 group with 96 VLBWIs. Compared with the pre-CIVID-19 group, the post-COVID-19 group had a significantly lower rate of MOM feeding within 28 days after birth and during hospitalization (P<0.05), a significantly lower volume of MOM feeding within 0-7 days, 0-14 days, and 0-28 days after birth (P<0.05), and significantly higher incidence rates of moderate-to-severe bronchopulmonary dysplasia and feeding intolerance (P<0.05). CONCLUSIONS: The COVID-19 pandemic has a significant impact on MOM feeding for VLBWIs, and there are significant reductions in the rate and volume of MOM feeding for VLBWIs within 28 days after birth, as well as a significant reduction in the rate of MOM feeding during hospitalization.

[Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation]. / äº§ç§‘å‡ºé™¢åŽå› ä¸¥é‡é«˜èƒ†çº¢ç´ è¡€ç—‡ä½é™¢æ–°ç”Ÿå„¿å ¥é™¢å‰éšè®¿æƒ å†µåŠéšè®¿ä¾ä»Žæ€§å½±å“å› ç´ çš„å¤šä¸­å¿ƒè°ƒæŸ¥.

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS: Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.

Prediction Models for Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review.

Objective: To provide an overview and critical appraisal of prediction models for bronchopulmonary dysplasia (BPD) in preterm infants. Methods: We searched PubMed, Embase, and the Cochrane Library to identify relevant studies (up to November 2021). We included studies that reported prediction model development and/or validation of BPD in preterm infants born at ≤32 weeks and/or ≤1,500 g birth weight. We extracted the data independently based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS). We assessed risk of bias and applicability independently using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Results: Twenty-one prediction models from 13 studies reporting on model development and 21 models from 10 studies reporting on external validation were included. Oxygen dependency at 36 weeks' postmenstrual age was the most frequently reported outcome in both development studies (71%) and validation studies (81%). The most frequently used predictors in the models were birth weight (67%), gestational age (62%), and sex (52%). Nearly all included studies had high risk of bias, most often due to inadequate analysis. Small sample sizes and insufficient event patients were common in both study types. Missing data were often not reported or were discarded. Most studies reported on the models' discrimination, while calibration was seldom assessed (development, 19%; validation, 10%). Internal validation was lacking in 69% of development studies. Conclusion: The included studies had many methodological shortcomings. Future work should focus on following the recommended approaches for developing and validating BPD prediction models.

Birth growth curves of neonates in high-altitude areas: A cross-sectional study.

Background: Since the current commonly used birth growth curves are unsuitable for neonates in high-altitude areas; this study aimed to establish birth growth curves for full-term neonates residing at 2,000-3,000 m. Methods: This cross-sectional study retrospectively analyzed the physical measurement data of 1,546 full-term neonates delivered at the Red Cross Hospital of Qinghai province, China, from July 2021 to April 2022. The percentile curves of birth weight, length, and head circumference of neonates of different gestational ages and genders were developed using curve fitting. The newly developed birth-weight percentile reference was compared with the INTERGROWTH-21st Neonatal Growth Curve (International Standard) and the Chinese Neonate Growth Curve (Chinese Standard). Results: The median birth weight, length, and head circumference of the study population were 3,200 g, 52.0 cm, and 32.8 cm, respectively, except for the group with a gestational age of 37 weeks. The growth indicators of male infants in all groups were higher than those of the female infants (P < 0.05). We found differences between the newly developed birth-weight percentile curves in the high-altitude areas and the International and Chinese Standards. Conclusion: Establishing birth growth curves corresponding to altitude may be more suitable than the existing standards for local medical staff to conduct health assessments of neonates.

Reference Interval for Pulse Oxygen Saturation in Neonates at Different Altitudes: A Systematic Review.

Introduction: The reference interval for pulse oxygen saturation (SpO2) in neonates born at high altitudes has not been defined to date. The purpose of this study was to systematically review published studies and determine the reference interval of SpO2 in neonates at different altitudes. Methods: Databases of PubMed, Embase, Cochrane Library, Clinicaltrials.Gov, Chinese National Knowledge Infrastructure Database, Wanfang Database, Chinese Science Technology Journals Database, and Chinese Clinical Trial Registry were searched for studies reporting SpO2 in healthy neonates at different altitudes. Retrieval time was from inception of the database to August 16, 2021. The Agency for Healthcare Research and Quality checklist was used to evaluate the quality of studies. Python v3.8 was used to analyze the data. This systematic review was drafted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Seven cross-sectional studies, published between 1991 and 2020, were identified. They were from US, Mexico, Israel, Ecuador, and China. Three studies were rated as high quality and four as moderate quality. The mean SpO2 (with standard deviation or standard error) of neonates born in 40 different altitudes (ranging from 25 meters to 3,100 meters) were obtained. The prediction equation for calculation of the lower limit of the reference interval was established, and the reference intervals for SpO2 at different altitudes were determined. Conclusions: In healthy neonates, the lower limit of the reference interval of SpO2 decreases with increase in altitude. High-quality prospective studies are need to confirm our findings.

A multicenter retrospective study on survival rate and complications of very preterm infants. / æžæ—©äº§å„¿å­˜æ´»çŽ‡å’Œå¹¶å‘ç—‡çš„å¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications. METHODS: The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants. RESULTS: A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25+6 weeks, 26-26+6 weeks, 27-27+6 weeks, 28-28+6 weeks, 29-29+6 weeks, 30-30+6 weeks, and 31-31+6 weeks had a survival rate of 32.5%, 60.6%, 68.0%, 82.9%, 90.1%, 92.3%, and 94.8% respectively. The survival rate tended to increase with the gestational age (P<0.05) and the survival rate without serious complications in each gestational age group was 7.5%, 18.1%, 34.5%, 52.2%, 66.7%, 75.7%, and 81.8% respectively, suggesting that the survival rate without serious complications increased with the gestational age (P<0.05). The multivariate logistic regression analysis showed that high gestational age, high birth weight, and prenatal use of glucocorticoids were protective factors against death in very preterm infants (P<0.05), and 1-minute Apgar score ≤3 was a risk factor for death in very preterm infants (P<0.05); high gestational age and high birth weight were protective factors against serious complications in very preterm infants who survived (P<0.05), while 5-minute Apgar score ≤3 and maternal chorioamnionitis were risk factors for serious complications in very preterm infants who survived (P<0.05). CONCLUSIONS: The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.

[A clinical analysis of sepsis in very low birth weight infants].

OBJECTIVE: To study the incidence and clinical features of sepsis in very low birth weight (VLBW) infants. METHODS: The clinical data were collected from VLBW infants, with a birth weight of < 1 500 g, who were admitted to the Department of Neonatology, Maternity Hospital Affiliated to Nanjing Medical University, from January 2019 to June 2020. The incidence of sepsis, distribution of pathogenic bacteria, and risk factors for sepsis were analyzed. RESULTS: A total of 369 infants were enrolled, and 138 infants had sepsis, among whom 84 had early-onset sepsis (EOS) and 54 had late-onset sepsis (LOS). Enterococcus faecalis (24%) and Streptococcus (21%) were the main pathogenic bacteria in infants with EOS, and Staphylococcus (41%) and Enterobacter (29%) were the main pathogenic bacteria in infants with LOS. The incidence of EOS and LOS decreased with the increase of gestational age and birth weight (P < 0.05). The multivariate logistic regression analysis showed that a high birth weight was a protective factor against EOS (OR=0.996, 95%CI:0.993-0.998, P < 0.05), while vaginal delivery (OR=2.781, 95%CI:1.190-6.500, P < 0.05) was a risk factor for EOS, and long duration of parenteral nutrition was a risk factor for LOS (OR=1.129, 95%CI:1.067-1.194, P < 0.05). CONCLUSIONS: Enterococcus faecalis is the most common pathogenic bacteria for EOS, and Staphylococcus is the most common pathogenic bacterium for LOS in VLBW infants. A high birth weight may reduce the risk of EOS in VLBW infants, while vaginal delivery may increase the risk of EOS. Prolonged parenteral nutrition may increase the risk of LOS.

[Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis].

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (n=1 184), tracheal intubation (n=166), and extensive cardiopulmonary resuscitation (ECPR; n=116). The three groups were compared in terms of general information and clinical outcomes. RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (P < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased (P < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased (P < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications (P < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group (P < 0.05). CONCLUSIONS: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.

Causes of severe neonatal hyperbilirubinemia: a multicenter study of three regions in China.

BACKGROUND: Available evidence suggests that our country bear great burden of severe hyperbilirubinemia. However, the causes have not been explored recently in different regions of China to guide necessary clinical and public health interventions. METHODS: This was a prospective, observational study conducted from March 1, 2018, to February 28, 2019. Four hospitals in three regions of China participated in the survey. Data from infants with a gestational age ≥ 35 weeks, birth weight ≥ 2000 g, and total serum bilirubin (TSB) level ≥ 17 mg/dL (342 µmol/L) were prospectively collected. RESULTS: A total of 783 cases were reported. Causes were identified in 259 cases. The major causes were ABO incompatibility (n = 101), glucose-6-phosphate dehydrogenase deficiency (n = 76), and intracranial hemorrhage (n = 70). All infants with glucose-6-phosphate dehydrogenase deficiency were from the central south region. Those from the central south region had much higher peak total bilirubin levels [mean, 404 µmol/L; standard deviation (SD), 75 µmol/L] than those from the other regions (mean, 373 µmol/L; SD, 35 µmol/L) (P < 0.001). CONCLUSIONS: ABO incompatibility was the leading cause in the east and northwest regions, but cases in the central south region were mainly caused by both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency, and infants in this region had a much higher peak total bilirubin level. Intracranial hemorrhage may be another common cause. More thorough assessments and rigorous bilirubin follow-up strategies are needed in the central south region.

[Association of early nutrition deficiency with the risk of bronchopulmonary dysplasia: a Meta analysis].

OBJECTIVE: To systematically evaluate the association of early nutrition intake with the risk of bronchopulmonary dysplasia (BPD). METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database were searched for the observational studies on the association between early nutrition intake and BPD. RevMan 5.3 software was used to perform a Meta analysis of eligible studies. RESULTS: Eight observational studies were included, with 548 infants with BPD and 522 infants without BPD. The Meta analysis showed that the BPD group had a significantly lower caloric intake than the non-BPD group within the first week after birth and in the first 2 weeks after birth (P < 0.05). The BPD group had a significantly lower enteral nutrition intake than the non-BPD group (WMD=-18.27, 95%CI:-29.70 to -6.84, P < 0.05), as well as a significantly lower intake of carbohydrate, fat, and protein (P < 0.05). The BPD group had a significantly longer duration of parenteral nutrition than the non-BPD group (WMD=14.26, 95%CI:13.26-15.25, P < 0.05). CONCLUSIONS: Early nutrition deficiency may be associated with the development of BPD, and more attention should be paid to enteral feeding of infants at a high risk of BPD to achieve total enteral feeding as soon as possible.

[Influence of twin pregnancy by assisted reproductive technology on neonatal outcomes].

OBJECTIVE: To study the influence of twin pregnancy by assisted reproductive technology (ART) versus twin pregnancy by spontaneous conception (SC) on neonatal outcomes. METHODS: A retrospective analysis was performed for the clinical data of 3 356 live twins with a gestational age of ≥24 weeks who were born in Nanjing Maternal and Child Health Hospital from 2017 to 2019, with 2 006 twins (1 003 pairs) in the ART group and 1 350 (675 pairs) in the SC group. The two groups were compared in terms of the mother's general information and pregnancy comorbidities and the general information, diseases, and outcomes of neonates. RESULTS: Compared with the SC group, the ART group had a significantly higher maternal age (P < 0.05) and significantly higher rates of primiparity, cesarean section, and cervical cerclage (P < 0.05). Compared with the SC group, the ART group had significantly higher incidence rates of maternal pregnancy comorbidities including hypertension, gestational diabetes, and postpartum hemorrhage (P < 0.05). Compared with the SC group, the ART group had a significantly lower mean gestational age of neonates (P < 0.05) and a significantly higher proportion of very-low-birth-weight infants (6.8% vs 5.8%, P < 0.05), while ART did not increase the risks of preterm birth and low Apgar score. There were no significant differences between the two groups in the mortality rate of neonates and the incidence rates of neonatal diseases including respiratory distress syndrome, stage II/III necrotizing enterocolitis, bronchopulmonary dysplasia, and grade III-IV intracranial hemorrhage (P > 0.05). CONCLUSIONS: Compared with twin pregnancy by SC, twin pregnancy by ART does not increase the neonatal mortality rate and risk of adverse outcomes.

[An investigation of severe neonatal hyperbilirubinemia in 13 hospitals of Jiangsu Province, China].

OBJECTIVE: To investigate the incidence of severe neonatal hyperbilirubinemia and the management on the treatment and follow-up of this disease in Jiangsu Province, China. METHODS: The neonates with severe hyperbilirubinemia who were admitted to 13 hospitals in Jiangsu Province from January to December, 2018, were enrolled as subjects. A retrospective analysis was performed on their mediacal data and follow-up data. RESULTS: In 2018, 740 neonates with severe hyperbilirubinemia were reported from the 13 hospitals in Jiangsu Province, accounting for 2.70% (740/27 386) of the total number of neonates admitted to the department of neonatology. Among these neonates, 620 (83.8%) had severe hyperbilirubinemia, 106 (14.3%) had extremely severe hyperbilirubinemia, and 14 (1.9%) had hazardous hyperbilirubinemia. Four neonates (0.5%) were diagnosed with acute bilirubin encephalopathy. A total of 484 neonates (65.4%) were readmitted due to severe hyperbilirubinemia after discharge from the delivery institution, with a median age of 7 days, among whom 214 (44.2%) were followed up for jaundice at the outpatient service before readmission, with a median age of 6 days at the first time of outpatient examination. During hospitalization, 211 neonates (28.5%) underwent cranial MRI examinations, among whom 85 (40.3%) had high T1WI signal in the bilateral basal ganglia and the globus pallidus; 238 neonates (32.2%) underwent brainstem auditory evoked potential examinations, among whom 14 (5.9%) passed only at one side and 7 (2.9%) failed at both sides. The 17 neonates with acute bilirubin encephalopathy or hazardous hyperbilirubinemia were followed up. Except one neonate was lost to follow-up, and there were no abnormal neurological symptoms in the other neonates. CONCLUSIONS: Neonates with severe hyperbilirubinemia account for a relatively high proportion of the total number of neonates in the department of neonatology. Jaundice monitoring and management after discharge from delivery institutions need to be strengthened. For neonates with severe hyperbilirubinemia, relevant examinations should be carried out more comprehensively during hospitalization and these neonates should be followed up comprehensively and systematically after discharge.

Circular RNAs are abundant and dynamically expressed during the embryonic lung development of C57BL/6 mice.

Circular RNAs (circRNAs), a novel type of endogenous RNAs, can function as microRNA (miRNA) sponges capable of regulating gene transcription, binding to RNA-associated proteins, and even encoding proteins. CircRNAs are involved in various cell behaviors, such as proliferation and apoptosis. The mouse model has also been demonstrated to be similar to that of humans in many studies. To explore the profile of circRNAs during embryonic lung development and their potential functions in lung development-related diseases, mouse embryos at the pseudoglandular phase, canalicular phase, saccular phase, and alveolar phase were collected. High-throughput sequencing was then used to identify a total of 1,735 circRNAs (junction reads ≥5 and p < 0.05). It is well known that the functions of circRNAs are related to host genes. In our study, bioinformatics analysis indicated that the screened host genes were closely associated with lung development and included the Hippo signaling pathway, PI3K-Akt signaling pathways, and TGF-ß signaling pathways. Moreover, miRNA sponges are another mechanism involved in lung development. Therefore, we predicted many miRNAs binding to circRNAs, such as miR-17 and miR-20, using the TargetScan and miRanda databases. Previously, miRNAs were proven to be necessary for lung development. The peak expression of circRNAs is distributed at different time points, suggesting their involvement in different stages of embryonic mouse lung development.

Profiles analysis reveals circular RNAs involving zebrafish physiological development.

Recent studies have found that known functions of circular RNAs (circRNAs) include sequestration of microRNAs (miRNAs) or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. The zebrafish model is also demonstrably similar to humans in many studies. To explore the changes in circRNAs during embryonic development and to further research the mechanism of action of circRNAs in development-related diseases, Zebrafish embryos at the blastula period, gastrula period, segmentation period, throat stage, and incubation period were collected. Illumina deep-sequencing technology and CircRNA Identifier (CIRI) algorithm were used to detect circRNAs. In total, we identified 1,028 circRNAs (junction reads ≥5 and p < 0.05). Considering that the function of circRNAs is related to host genes, a bioinformatics analysis revealed these differentially expressed host genes are involved in NOTCH signaling pathways, cardiovascular system development, retinal ganglion cell axon guidance, and so on. Moreover, circRNAs can participate in biological regulation through the function of miRNA sponges. TargetScan and miRanda were used to predict 73 miRNAs binding to circRNAs such as miR-19b, miR-124, and so on. Some miRNAs play important roles in embryogenesis. The peak expression of circRNAs is distributed at different time points, suggesting that it may be involved in embryogenesis at different stages. Our study provides a foundation for understanding the dynamic regulation of circRNA transcriptomes during embryogenesis and identifies novel key circRNAs that might control embryonic development in a zebrafish model.

Differential Expression of CircRNAs in Embryonic Heart Tissue Associated with Ventricular Septal Defect.

Objectives: To explore and validate the differential expression of circRNAs in the myocardium of congenital ventricular septal defect (VSD) and to explore a new avenue of research regarding the pathological mechanisms of VSD. Methods: We detected circRNAs expression profiles in heart tissues taken from six aborted fetuses with VSD and normal group using circRNA microarray. Some differentially expressed circRNAs were studied by bioinformatics analysis. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm these results. Results: This study found abundant circRNAs in the myocardium taken from individuals in the normal group and the VSD group. After that, totally 6234 differentially expressed circRNAs between the normal group and the VSD group were confirmed (Fold change ≥ 2.0; p < 0.05). Then, this research carried out bioinformatics analysis and predicted the potential biological functions of circRNAs. Finally, the over-expression of hsa_circRNA_002086 and under-expression of hsa_circRNA_007878, hsa_circRNA_100709, hsa_circRNA_101965, hsa_circRNA_402565 were further validated by qRT-PCR. Conclusions: There is a significant difference in expression of the circRNA in cardiac tissue from VSD group compared to the normal group. Combined with the microarray results and previous researches, circRNAs may contribute to the occurrence of VSD by acting as miRNA sponges or by binding proteins, these possible roles for circRNAs in VSD require elucidation in additional studies.

[Effect of breastfeeding quality improvement on breastfeeding rate in very low birth weight and extremely low birth weight infants].

OBJECTIVE: To study the effect of breastfeeding quality improvement on the breastfeeding rate in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants in the neonatal intensive care unit (NICU). METHODS: A retrospective analysis was performed for the clinical data of VLBW and ELBW infants who were admitted from July 2014 to July 2015 (pre-improvement group) and those who were admitted from August 2015 to June 2016 after the implementation of breastfeeding quality improvement measures (post-improvement group). The parameters including condition of breastfeeding (breastfeeding rate, breastfeeding amount, and breastfeeding time), duration of parenteral nutrition, time to enteral feeding, and incidence of feeding intolerance were compared between the two groups. RESULTS: The implementation of breastfeeding quality improvement measures significantly increased breastfeeding rate and amount, significantly shortened time to addition of human milk fortifier, duration of parenteral nutrition, and time to enteral feeding, and significantly decreased the incidence of feeding intolerance. CONCLUSIONS: Breastfeeding quality improvement measures can increase breastfeeding rate in the NICU and decrease gastrointestinal complications in preterm infants.

Peptidomic Analysis of Amniotic Fluid for Identification of Putative Bioactive Peptides in Ventricular Septal Defect.

BACKGROUND: Ventricular septal defect (VSD) is one of the most common congenital heart diseases and to date the role of peptides in human amniotic fluid in the pathogenesis of VSD have been rarely investigated. METHODS: To gain insight into the mechanisms of protein and peptides in cardiovascular development, we constructed a comparative peptidomic profiling of human amniotic fluid between normal and VSD fetuses using a stable isobaric labeling strategy involving tandem mass tag reagents, followed by nano liquid chromatography tandem mass spectrometry. RESULTS: We identified and quantified 692 non-redundant peptides, 183 of which were differentially expressed in the amniotic fluid of healthy and VSD fetuses; 69 peptides were up regulated and 114 peptides were down regulated. These peptides were imported into the Ingenuity Pathway Analysis (IPA) and identified putative roles in cardiovascular system morphogenesis and cardiogenesis. CONCLUSION: We concluded that 35 peptides located within the functional domains of their precursor proteins could be candidate bioactive peptides for VSD. The identified peptide changes in amniotic fluid of VSD fetuses may advance our current understanding of congenital heart disease and these peptides may be involved in the etiology of VSD.

Bioinformatic and Expression Analysis of Ventricular Septal Defect-associated Long Non-coding RNA TUC40-.

OBJECTIVE: To explore the potential role of TUC40- in human and mouse embryonic heart development. METHODS: Bioinformatics databases including NCBI,UCSC,and Uniprot and software including Clustal,DNAMAN,and MEGA 6 were used to collect information of TUC40- and uc.40-. The expression profile at key time points of heart development was investigated by strand-specific quantitative real time polymerase chain reaction. RESULTS: Uc.40- was conservative in sequence, genomic location, and transcription factor binding sites across human and mouse. Pbx1/TUC40- showed negative trend during embryonic mouse heart maturation. CONCLUSIONS: Various levels of conservation of uc.40- suggests similar functions of TUC40- in these two species. TUC40- may play its roles in human and mouse embryonic heart development by regulating Pbx1.