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Bronchopulmonary dysplasia(BPD)is a common chronic respiratory disease, with high mortality and poor long-term prognosis in surviving children, and there is currently no effective intervention.Breastfeeding reduces the incidence of BPD.These depend on a variety of bioactive substances in human breast milk, such as immunoglobulins, oligosaccharides, exosomes, etc.Exosomes are nano-like vesicle bodies secreted by cells, which participate in information transmission and functional regulation between cells.They have high affinity for the body and can tolerate digestion of gastrointestinal enzymes and stomach acid.These enable them to target lung, liver and other organs smoothly.They are expected to become a new method for the prevention and treatment of BPD.
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Objective:To study the clinical features and high-risk factors of early-onset sepsis (EOS) in extremely preterm and super preterm infants.Methods:Retrospective study.Clinical data of extremely preterm and super preterm infants with the gestational age < 32 weeks were obtained from the clinical database of breast milk quality improvement registration in the Woman′s Hospital of Nanjing Medical University between January 2019 and December 2019.EOS cases were enrolled in the EOS group, and the remaining were enrolled in the control group.Risk factors for EOS, distribution of pathogenic bacteria, clinical features, complications, and outcomes between groups were analyzed.Measurement data were compared between the independent sample t-test.Counting data between groups were compared by the Chi- square test, corrected Chi- square test or Fisher′ s exact test.Multivariable Logistic regression model was used to analyze the risk factors of EOS in extremely and super preterm infants. Results:A total of 347 eligible neonates were recruited, including 22 neonates with EOS and 325 neonates without EOS.The incidence rate of EOS was 6.3%.Multivariate Logistic regression analysis showed that cesarean delivery was the protective factor for EOS ( OR=0.277, 95% CI: 0.091-0.847); while maternal prenatal infection ( OR=2.750, 95% CI: 1.053-2.908), fetid amniotic fluid ( OR=3.878, 95% CI: 1.344-11.187), chorioamnionitis ( OR=4.363, 95% CI: 1.552-12.236) and intubation ( OR=3.883, 95% CI: 1.133-13.306) were risk factors for EOS.A total of 22 strains of pathogenic bacteria were cultured in the EOS group, including 14 strains (63.6%) of Gram-positive bacteria, 7 strains (31.8%) of Gram-negative bacteria and 1 strain (4.6%) of fungus.The acute respiratory distress syndrome (54.5%), poor peripheral circulation perfusion (54.5%), mental depression (50.0%), and procalcitonin>0.5 mg/L (40.9%) were the main clinical features of EOS.Compared with the control group, extremely preterm and super preterm infants with EOS had a significantly higher rate of septic shock, disseminated intravascular coagulation, severe intraventricular hemorrhage (≥Ⅲ), acute respiratory distress syndrome (ARDS), and bronchopulmonary dysplasia( χ2=36.696, 33.255, 13.534, 95.455 and 3.886, respectively; all P<0.05). Conclusions:Maternal perinatal infection, odor amniotic fluid, chorioamnionitis and delivery room tracheal intubation are high-risk factors for preterm and super preterm infants with EOS, which can be prevented by cesarean section.Gram-positive cocci are the main pathogenic bacteria of EOS.ARDS and poor peripheral circulation perfusion are the main clinical manifestations of EOS, which increase the occurrence of severe intracranial hemorrhage and other complications.
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Objective:To study the predictive value of total serum bilirubin (TSB) and the ratio of bilirubin to albumin (B/A) in neonatal acute bilirubin encephalopathy (ABE).Methods:Neonates with extremely severe hyperbilirubinemia (TSB≥425 μmol/L) treated in the Nanjing Maternal and Child Health Hospital, Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Northwest Women and Children's Hospital, Yinchuan Maternal and Child Health Hospital and Liaocheng People's Hospital from March 2018 to August 2019 were selected as prospective subjects for this study. According to the score of brain injury induced by bilirubin, the subjects were divided into ABE group and non-ABE group, and the predictive value of TSB peak and B/A for neonatal ABE were analyzed.Results:A total of 194 infants with extremely severe hyperbilirubinemia were recruited in this study, including 20 in ABE group and 174 in non-ABE group. The peak value of bilirubin ranged from 427 to 979 μmol/L. The optimal critical values of TSB peak value and B/A for ABE prediction were 530 μmol/L and 9.48, respectively. The sensitivity and specificity of ABE prediction were 85.0% and 92.8% when combined with TSB peak and B/A values.Conclusions:TSB peak combined with B/A value can effectively identify neonatal ABE. When the TSB peak value was greater than 530 μmol/L and the B/A value was greater than 9.48, the neonates had a higher risk of neonatal ABE.
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Breast milk contains a variety of bioactive components, which play a vital role in disease prevention and treatment.Among them, circular RNA(circRNA), which is a closed ring structure formed by covalent bonds, has aroused interest because of its conservation and stability.Pediatric researchers should attach importance to studies on circRNA in breast milk, as they may bring new inspiration for breast milk functions.In this article, characteristics and functions of circRNA in breast milk will be investigated, and its research and prospects will be discussed.
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Objective:To study the risk factors, cerebral hemodynamics and clinical outcomes of extremely and very preterm infants with severe intraventricular hemorrhage (IVH).Methods:From January 2019 to December 2019, premature infants with gestational age (GA) <32 w admitted to our hospital were assigned into severe IVH group and non-severe IVH group. Risk factors for severe IVH were analyzed. According to clinical outcomes, severe IVH group was further assigned into improvement subgroup and no-improvement subgroup. Cerebral hemodynamic parameters were compared between the two groups.Results:A total of 346 eligible neonates were enrolled in this study. The incidence of severe IVH was 11.0% (38 cases). The incidences of Grade Ⅲ and Ⅳ IVH were 8.7% (30/346) and 2.3% (8/346), respectively. Multivariate logistic regression analysis showed that CA < 28 w ( OR=4.365, 95% CI 1.055~18.054), 5 min Apgar score ≤7 ( OR=8.749, 95% CI 2.214~36.042), chorioamnionitis ( OR=3.245, 95% CI 1.127~9.344), PaCO 2 fluctuation within 1 h >25 mmHg ( OR=7.728, 95% CI 1.738~80.907) and vasoactive drugs usage ( OR=10.883, 95% CI 3.746~31.621) were the risk factors of severe IVH. 20 cases in severe IVH group were improved at discharge and 12 cases showed no improvement at discharge. Improvement subgroup showed quicker reduction of the middle cerebral artery flow resistance and faster recovery of the mean flow velocity than the no-improvement subgroup. Conclusions:GA <28 w, 5 min Apgar score ≤7, chorioamnionitis, PaCO 2 fluctuation within 1 h >25 mmHg and vasoactive drugs usage are risk factors of severe IVH in extremely and very preterm infants. Cerebral hemodynamic monitoring may provide initial assessment for the clinical outcomes for severe IVH.
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The initiation of lactation is the critical initial event contributing to breastfeeding. It is of great significance for maternal lactation and neonatal access to breast milk. However, various factors limit the successful initiation of lactation and increase the risk of poor neonatal prognosis. We provide an overview of the mechanism, significance, method, time, and factors that influence lactation initiation behavior, and summarize related guidelines aiming to gain more insight into the lactation initiation behavior to promote maternal lactation and improve neonatal prognosis.
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Objective:To evaluate the outcomes of cardiopulmonary resuscitation in the delivery room (DR-CPR) at birth for very/extremely low birth weight infants (VLBWI/ELBWI).Method:PubMed, Embase, Cochrane Library, CNKI, VIP database and Wanfang database were searched. The search time limit is from the establishment of the database to October 26, 2020. Search and screen all the literature on the short-term and long-term outcomes of VLBWI/ELBWI who require DR-CPR and conduct quality evaluations. Review Manager 5.3 software was used to perform the Meta analysis. Egger's test in Stata Software 15.0 was used to draw a funnel plot and validate publication bias.Result:A total of 16 studies were included, all in English. 5 661 VLBWI/ELBWI received DR-CPR, and 73 438 VLBWI/ELBWI did not receive DR-CPR. The Meta analysis showed: DR-CPR for VLBWI/ELBWI was associated with an increased risk of mortality ( RR=2.30, 95% CI 1.89~2.82, P<0.05), grade 3 or 4 intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) ( RR=1.92, 95% CI 1.56~2.36, P<0.05),bronchopulmonary dysplasia (BPD) ( RR=1.18,95% CI 1.04~1.33, P<0.05), neurodevelopmental impairment (NDI) ( RR=1.25, 95% CI 1.14~1.38, P<0.05). However, it did not increase the risk of retinopathy of prematurity (>grade 2)( RR=1.31, 95% CI 0.96~1.79, P=0.09). The ELBWI was analyzed in subgroups, and the results were consistent with the overall results. Conclusion:CPR at birth for VLBWI/ELBWI was associated with higher risk of mortality, IVH (grade 3 or 4) or PVL, BPD, NDI.
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Objective To implement a continuous quality improvement (QI) initiative to increase the breastfeeding rate of mother's own milk(MOM) in very low birth weight infant (VLBWI) and extremely low birth weight infant (ELBWI) in neonatal intensive care unit (NICU) and to evaluate its impact on the morbidity of these infants. Methods A retrospective analysis was performed to analyze the clinical data of VLBWIs and ELBWIs who were admitted to the Nanjing Maternity Hospital Affiliated to Nanjing Medical University from July 1, 2014 to December 31, 2017 (n=587). The QI initiative was implemented in the hospital on August 1, 2015, the effect was assessed at the end of 2016 and the QI process was adjusted from 2017 to ensure continuous quality improvement of breastfeeding, based on which the 587 infants were divided into three groups: those in pre-QI group admitted from July 1, 2014 to July 31, 2015 (n=141), post-QI group admitted from August 1, 2015 to December 31, 2016 (n=243) and continuous QI group admitted from January 1, 2017 to December 31, 2017 (n=203). Differences in breastfeeding rates of MOM, the time of first breastfeeding of MOM, duration of parenteral nutrition, time to achieve full enteral feeding, average length and costs in NICU stay and the incidence of feeding intolerance, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) were compared between the three groups. Statistical analysis was performed using analysis of variance, rank-sum test, Chi-square test and Bonferroni test. Results Compared with the pre-QI group, both the post-QI and continuous QI groups had significantly increased breastfeeding rates of MOM [0-7 d: 38.2%(0.0%-69.0%) vs 72.8%(42.6%-84.2%) and 75.5%(49.8%-87.2%);0-14 d: 37.8%(29.9%-80.5%) vs 91.9%(79.1%-96.0%) and 92.0%(71.0%-96.8%); 0-28 d: 58.2%(30.0%-90.1%) vs 96.6%(90.3%-98.9%) and 96.4%(83.1%-98.9%); during hospitalization: 50.0%(30.0%-85.5%) vs 96.6%(89.5%-99.1%) and 96.8% (83.0%-99.3%); all P<0.05] and volume of MOM intake [0-7 d: 31 (0-397) vs 82 (0-506) and 95 (0-510) ml; 0-14 d: 198 (0-1 596) vs 622 (0-1 828) and 717 (0-1 868) ml; 0-28 d: 1 458 (0-4 960) vs 2 707 (0-7 074) and 2 893 (0-10 238) ml; during hospitalization: 2 000 (0-18 767) vs 4 071 (0-22 961) and 3 979 (0-17 260) ml] within 7, 14 and 28 d after birth and during hospitalization. Moreover, the volume of MOM intake in the continuous QI group was higher than that in the post-QI group during the first 7 d after birth (all P<0.05). The time on first MOM breastfeeding in the post-QI and continuous QI groups were earlier than that in the pre-QI group [69 (16-633) and 68 (3-456) vs 73 (8-348) h, P<0.05]. Full enteral feeding was achieved earlier in the continuous QI group than the post- and pre-QI group [14 (5-40) vs 17 (6-53) and 19 (11-56) d, P<0.05]. The length of parenteral nutrition, incidence of feeding intolerance, BPD and LOS and hospital stay in the continuous QI group, post- and pre-QI group were 13(3-38), 15(8-50) and 17(11-39) d; 31.5%(64/203), 34.2%(83/243) and 47.5%(67/141); 8.9%(18/203), 20.1%(49/243) and 36.1%(51/141);31.5%(64/203), 35.0%(85/243) and 47.5%(67/141); 32 (1-73), 39 (10-93) and 34 (1-91) d, respectively. The length of parenteral nutrition and incidence of feeding intolerance and BPD in the continuous group were less than the pre-QI group, and the incidence of LOS and hospital stay were less than the post-QI group (all P<0.05). However, the post-QI group had longer hospital stay than the pre-QI group (P<0.05). Conclusions Continuous QI initiative improves MOM feeding rates and reduces the incidence of feeding intolerance, LOS and BPD in VLBWI and ELBWI.
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Objective To study the distribution of preterm infants' body temperature at admission and its effects on the clinical outcome.Method The distribution of preterm infants' body temperature at admission and its effects on their clinical outcome were searched in the Cochrane library,PubMed,Embase,Wanfang,CNKI,VIP from the initial establishment of these databases to June 2018.The quality of the included studies were assessed.STATA 12.0 software was used for statistical analysis.The odds ratio (OR) and 95% confidence interval(CI) were used for continuous variables.Result A total of 16 studies (including 15 clinical trials) with 47 113 cases were included.The incidences of different admission temperatures were as follows:<35℃:10.3% (7.6%~13.1%),<36℃:45.3% (35.0%~55.5%),<36.5℃:63.5% (51.8%~75.2%),36.5~37.4℃:35.1% (25.6%~44.7%),≥37.5℃:4.2% (2.6%~5.7%).Compared with normothermia (36.5~37.4℃),hypothermia (<35℃,35~35.9℃,36~36.4℃) increased the mortality,with the OR and 95%CI as follows:6.10(4.88~7.62),1.96(1.45~2.66),1.31(1.16~1.48);hyperthermia (≥37.5℃) was not associated with higher mortality (OR =0.98,95%CI 0.73~1.32,P=0.91).Compared with normothermia (36.5~37.4℃),hypothermia (<36℃) increased the risks of severe retinopathy of prematurity (ROP),necrotizing enterocolitis (NEC),sepsis,periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH),with the OR and 95%CI as follows:ROP:1.70(1.45~2.00),NEC:1.27(1.08~1.49),sepsis:1.44(1.28~ 1.61),PVL/IVH:1.26(1.07~1.48),but not the risk of bronchopulmonary dysplasia (BPD,OR =1.03,95%CI 0.76~1.38,P=-0.87).Compared with normothermia (36.5~37.4℃),the temperature between 36~36.4℃ did not increase the risk of severe ROP,NEC,BPD,sepsis,PVL/IVH,with the OR and 95%CI as follows:1.19(0.92~ 1.54),1.01(0.86~1.18),0.91(0.68~1.22),1.02(0.91~1.14),0.98(0.85~1.14).Conclusion Admission temperature of <35℃,35~35.9℃,and 36~36.4℃ increased the mortality risk compared with 36.5~37.4℃,and the lower admission temperature,the higher mortality risk.Admission hypothermia (<36℃) increased the risk of severe ROP,NEC,sepsis,PVL/IVH compared with normothermia (36.5~37.4℃).
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Neonatal medicine in China has been developing rapidly in recent years,but there is a considerable gap in clinical statistics and studies between China and developed countries.Since 1990s,some international neonatal homogeneity platforms such as the Vermont-Oxford Network and the Canadian Neonatal Network,in which a unified collaboration network database was applied,have been established to share the homogeneous data of all network databases in neonatal clinical and scientific research.These platforms have greatly promoted the progress of neonatal clinical studies in both Europe and America.Yet,we have not seen great breakthroughs in clinical big data analysis in neonatal medicine in China.Here,we discussed the critical role of establishing neonatal homogeneity platform in clinical and scientific research.
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Objective To explore the effects of quality improvement in delivery room resuscitation on very/extremely low birth-weight infants (VLBWI/ELBWI). Methods A retrospective analysis was performed to analyze the clinical data of VLBWI/ELBWI who were admitted to the Neonatal Intensive Care Unit (NICU) of Nanjing Maternity Hospital Affiliated to Nanjing Medical University from January to December 2015 (pre-improvement group, n=176) and of those who were admitted from January to December 2016 after the implementation of quality improvement program on delivery room resuscitation (post-improvement group, n=199). Several parameters were monitored, including resuscitation modalities [continuous positive airway pressure (CPAP) , peak inspiratory pressure (PIP)+positive end expiratory pressure (PEEP) with T-piece resuscitator and intubation rate in delivery room], neonatal body temperature and pH on NICU admission, respiratory outcomes, morbidity from intraventricular hemorrhage, necrotizing enterocolitis, retinopathy ofprematurity and hospitalization. Chi-square (or Fisher's exact test), t or rank Sum test was used for statistical analysis. Results There was no significant difference in gestational age, birth weight, gender proportion, delivery mode and Apgar scores between the two groups (all P>0.05). After implementing the quality improvement program, there was an increased overall usage of CPAP [85.9% (171/199) vs 66.3% (112/176), χ2=19.881, P0.05). The average admission temperature increased after launching the quality improvement program [M (P25-P75), 36.2 (35.8-36.5) vs 35.6 (35.4-35.7)℃ , Z= - 9.681, P<0.01]. The morbidities of pulmonary hemorrhage within one week after birth [1.5% (3/199) vs 5.1% (9/176),χ2=3.921] and grade Ⅲ / Ⅳ intraventricular hemorrhage [1.1% (2/199) vs 11.9% (21/176), χ2=33.885] decreased along with the improvement in delivery room resuscitation (both P<0.05). The duration of invasive ventilation decreased as well [3 (1-6) vs 4 (2-9) d, Z= - 2.286, P<0.05]. Conclusions Quality improvement in delivery room resuscitation measures standardizes the management of delivery room resuscitation and improves the clinical outcomes of VLBWI/ELBWI.
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Objective To analyze Holder pasteurization,temperature and duration of frozen,duration of continuous breast milk pumping and types of pumping tube on macronutrients and total energy in breast milk and the circadian variation of macronutrients and energy content of breast milk.Methods Two hundred and two breast milk samples were collected from healthy mothers of 188 infants who were hospitalized in Department of Pediatrics,Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University from April 2016 to December 2016.Fat,protein,carbohydrate and energy contents of the breast milk samples were detected both before and after various processes to analyze the influence of Holder pasteurization,frozen storage conditions (temperature and time),duration of continuous pumping and types of pumping tube and to observe the variations within a single day.Paired t-test,repeated-measures analysis of variance,one-way analysis of variance and LSD-t test were used for statistical analysis.Results The contents of fat,protein and energy in breast milk were significantly decreased [(3.69 ± 0.98) vs (4.22 ± 1.00) g/dl,t=9.405;(2.12 ± 0.34) vs (2.21 ± 0.34) g/dl,t=4.785;(69.77±9.35) vs (74.94±9.53) kcal/dl (1 kcal=4.184 kJ),t=9.470],while the carbohydrate content was increased [(6.66±0.17) vs (6.62±0.17) g/dl,t=-3.442] after Holder pasteurization comparing with those before (all P<0.01).Breast milk frozen at =80 ℃ had higher protein content than that frozen at-20 ℃ (Ftemperature=4.990,Ptemperature=0.027).Breast milk stored at-20 ℃ for 7,15,30,60 and 90 days showed significantly decreased fat,protein and energy contents as compared with those in fresh breast milk,while the carbohydrate contents in the breast milk samples stored at-20 ℃ for 15,30 and 60 days were significantly increased and that kept for 90 days were lower than those at 30 and 60 days (LSD-t test,P<0.05).Compared with fresh breast milk,breast milk stored at-80 ℃ showed significantly decreased fat,protein and energy contents at 60 d and 90 d,but increased carbohydrate content at 60 d (LSD-t test,P<0.05).Compared with fresh breast milk,breast milk which was pumped at 1,2 or 3 h through gastric tube (size 6,8 or 10) or transfusion connecting pipe had lower fat content (LSD-t test,P<0.05).Compared with fresh milk,breast milk had lower energy content on condition that it was pumped through gastric tube size 6 at 2 or 3 h or through gastric tube size 8 or 10 or transfusion connecting pipe at 1,2 or 3 h (LSD-t test,P<0.05).Breast milk secreted from 12:01 to 15:00 had higher fat and energy contents [(5.16±0.93) g/dl and (86.96±9.35) kcal/dl] than that secreted from 00:01 to 03:00[(4.54±0.75) g/dl and (80.77±7.75) kcal/dl],from 03:01 to 06:00 [(4.61 ±0.75) g/dl and (81.44±7.69) kcal/dl] or from 21:01 to 24:00 [(4.71 ± 0.88) g/dl and (82.44± 8.82) kcal/dl].Moreover,breast milk secreted from 09:01 to 12:00 had higher fat and energy contents [(5.01 ± 0.94) g/dl and (85.31 ± 9.62) kcal/dl] than that secreted from 00:01 to 03:00,and that secreted from 09:01 to 12:00 had higher fat contents than that secreted from 03:01 to 06:00 (LSD-t test,P<0.05).Conclusions Fresh breast milk is better than processed milk to meet the infantile need for growth and development.
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Objective To study the efficacy of T-piece resuscitator on the very preterm infants in the delivery room.Method Very preterm infants (gestational age 28 ~ 31 weeks) who needed positive pressure ventilation during delivery room resuscitation were included in the study between January 2010 and December 2015.Enrolled infants were randomly assigned to self-inflating bag group and T-piece group.Tracheal intubation ratio,duration of mechanical ventilation,continuous positive airway pressure (CPAP),supplementary oxygen through a nasal cannula and total oxygen requirement were compared between groups.The percentages of pneumothorax,sepsis,necrotizing enterocolitis (NEC),bronchopulmonary dysplasia (BPD),retinopathy of prematurity (ROP),intracranial hemorrhage and patent ductus arteriosus (PDA) between groups were also compared.Data were analyzed using independent sample t test and chi-square test.Result A total of 51 preterm infants were enrolled in this study,with 25 infants in the self-inflating bag group and 26 in the T-piece group.There was no statistically significant difference in the gender,gestational age,birth weight,Apgar scores,delivery mode and antenatal glucocorticoids between the two groups (P > 0.05).The ratio of intubation in T-piece group was significantly lower than that in self-inflating bag group (15.4% vs.44.0%,P < 0.05).Further more,duration of mechanical ventilation and total oxygen requirement in the T-piece group were significantly shorter than those in the self-inflating bag group [(4.2±2.8) dvs.(10.1 ±4.3) d,(36.2±14.7) dvs.(47.2±19.2) d,P<0.05].However,the duration of nasal CPAP and supplementary oxygen through a nasal cannula,the rate of pneumothorax,sepsis,NEC,BPD,ROP,intracranial hemorrhage and PDA did not differ significantly between groups (P > 0.05).Conclusion Compared with the self-inflating bag group,the use of the T-piece in delivery room decrease the rate of tracheal intubation and the duration of mechanical ventilation and total oxygen requirement.
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Objective To evaluate the safety of cytomegalovirus (CMV) DNA positive fresh breast milk in low birth weight infants (< 1500 g). Methods The low birth weight infants (< 1500 g) admitted to hospital were enrolled from May 1, 2015 to Dec. 31, 2015 and from May 1, 2016 to Dec. 31, 2016. All the subjects were breast fed by own mother's milk during the period of hospitalization, and was supplemented with the donated breast milk when the mothers' breast milk was insufficient. The CMV DNA content in mother's milk was measured by quantitative polymerase chain reaction (FQ-PCR) at two weeks after birth. If the CMV DNA in mother's milk was positive, during the period of May 1, 2015 to Dec 31, 2015, the milk was pasteurized before fed;during the period of May 1, 2016 to Dec. 31, 2016, the milk was fed without treatment. The differences of infections, liver injury, and hearing impairment among the untreated CMV DNA positive milk group, the pasteurized CMV DNA positive milk group, the untreated CMV DNA negative milk group were compared. Results A total of 222 low birth weight infants (<1500 g) were included, among whom 21 infants had birth weight < 1000 g. The CMV DNA was detected positive in 132 (59.46%) mother's milk. Sixty-seven infants were in the untreated CMV DNA positive milk group, 65 infants in the pasteurized CMV DNA positive milk group, and 90 infants in untreated CMV DNA negative group milk group. There were no significantly differences in gestational age, birth weight and sex among three groups. There were also no significant differences in the incidence of neonatal pneumonia, late sepsis, intestinal infection, liver damage, and hearing loss among three groups (P>0.05). Conclusions Feeding CMV DNA positive mother's breast milk does not adversely affect the clinical outcomes in low birth weight infants during hospitalization.
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Objective To evaluate the safety and effects of feeding very low birth weight infants and extremely low birth weight infants with human donors' milk in China.Methods One hundred and ninety-nine very low birth weight infants and extremely low birth weight infants (VLBWI/ELBWI) admitted to NICU in Nanjing Maternity and Child Health Care Hospital were analyzed retrospectively (from August 1,2013 to July 31,2014) one year before and one year after the establishment of human donors' milk bank.Only 1 infant's parents(1/199 cases) refused to use donor milk,and 198 infants were fed with donors' milk since their own mothers' milk was unavailable.One hundred and forty-eight infants admitted to NICU from August 1,2012 to July 31,2013 were chosen as the control group,who were fed with formula milk since their own mothers' milk was unavailable.The mortality,incidence of necrotizing enterocolitis (NEC) and sepsis,time to full enteral feeding and hospital stay between 2 groups were analyzed.Results One year before the establishment of breast milk bank,there were 148 cases of very low or extremely low birth weight infants receiving mixed feeding,and 16 cases of them had neonatal necrotizing enterocolitis,the incidence rate was 10.81%.Since the establishment of human milk bank,187 women donated breast milk in the first year and 260 555 mL of human milk were collected and delivered.Only 1 infant (1/199 cases) refused to use donor milk,and 198 infants were fed with donors' milk since their own mothers' milk was unavailable.Nine babies with VLBWI/ELBWI were diagnosed as NEC in donor milk feeding group,and 16 cases were diagnosed as NEC in formula-feeding group.The incidence rate of NEC was lower in the donor-milk-feeding group (4.52% vs 10.81%,x2 =5.02,P < 0.05).Donor-milk-feeding group reached full enteral feeding[(16.4 ± 5.3) d vs (18.2 ± 6.2) d,t =2.84,P < 0.05] and had shorter period of hospital stay[(35.1 ± 9.5) d vs (37.3 ± 10.4) d,t =2.05,P < 0.05] compared with formula feeding group.The mortality and incidence of sepsis had no difference between 2 groups (all P > 0.05).Conclusions Donors' breast milk is associated with a lower risk of NEC,sooner full enteral feeding and shorter hospital stay.Further research is needed to confirm these findings and measure the growth and long term neurodevelopment effects of donors' breast milk.
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Objective To explore the effects of miR -30c over -expression on early cardiac development of zebrafish.Methods The single -cell -stage zebrafish embryos were micro -injected with 3 different concentrations of miR -30c mimics in order to model the miR -30c over -expressed animal.Besides,the effects of miR -30c overex-pression on cardiac development were investigated.The mortality rate and the heart rate were assessed.Beside,the gross morphology and heart morphology of the zebrafish were observed.Moreover,the molecular mechanisms underlying miR -30c function in zebrafish cardiac development was explored,and in -situ hybridization was performed.Results Compared with the wild -type embryos,the mortality rate of zebrafish was increased with the rising miR -30c concen-tration.Furthermore,when the miR -30c mimic concentration was up to 8 μmol/L,the mortality rate reached 80% at 96 h post -fertilization.Simultaneously,the heart rate,which was viewed as an important index to cardiac function,was decreased.Moreover,the pericardial edema was getting worse over time with increasing concentration of overexpression. Then,the cardiac specific gene expression on the zebrafish embryos by whole -mount in situ hybridization was ex-plored.The area of the cardiac chamber was extended and the heart tube looping was negatively affected.Besides,the expression of atrioventricular canal marker genes was absent in zebrafish embryos from miR -30c over -expression groups.Conclusion miR -30c can impact the early cardiac development of zebrafish.
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MicroRNAs (miRNAs) are small, non-coding single-stranded RNAs that suppress protein expression by binding to the 3′ untranslated regions of their target genes. Many studies have shown that miRNAs have important roles in congenital heart diseases (CHDs) by regulating gene expression and signaling pathways. We previously found that miR-30c was highly expressed in the heart tissues of aborted embryos with ventricular septal defects. Therefore, this study aimed to explore the effects of miR-30c in CHDs. miR-30c was overexpressed or knocked down in P19 cells, a myocardial cell model that is widely used to study cardiogenesis. We found that miR-30c overexpression not only increased cell proliferation by promoting cell entry into S phase but also suppressed cell apoptosis. In addition, we found that miR-30c inhibited dimethyl sulfoxide-induced differentiation of P19 cells. miR-30c knockdown, in contrast, inhibited cell proliferation and increased apoptosis and differentiation. The Sonic hedgehog (Shh) signaling pathway is essential for normal embryonic development. Western blotting and luciferase assays revealed that Gli2, a transcriptional factor that has essential roles in the Shh signaling pathway, was a potential target gene of miR-30c. Ptch1, another important player in the Shh signaling pathway and a transcriptional target of Gli2, was downregulated by miR-30c overexpression and upregulated by miR-30c knockdown. Collectively, our study revealed that miR-30c suppressed P19 cell differentiation by inhibiting the Shh signaling pathway and altered the balance between cell proliferation and apoptosis, which may result in embryonic cardiac malfunctions.
Subject(s)
Female , Pregnancy , Aborted Fetus , Apoptosis , Blotting, Western , Cell Differentiation , Cell Proliferation , Embryonic Development , Gene Expression , Heart , Heart Diseases , Heart Septal Defects, Ventricular , Hedgehogs , Luciferases , MicroRNAs , RNA , S Phase , Untranslated RegionsABSTRACT
Objective To explore the effects of microRNA(miRNA)- 30c knockdown on proliferation,diffe-rentiation of P19 cells. Methods miRNA - 30c knockdown plasmid(miRNA - 30c knockdown group)or no - load vector(negative control group)was transfected into P19 cells by lipo2000 and stable cell lines were selected by Blastici-din;Dual luciferase reporter gene system was used to confirm miRNA - 30c knockdown. Cell counting kit - 8(CCK - 8) assay was adopted to detect cell proliferation activity. An inverted microscope was used to observe morphological chan-ges of P19 cell differentiation. Cells were induced to differentiated to myocardiocyte with dimethyl sulfoxide(DMSO). Differentiation marker genes including cTnT,NKX2. 5,GATA4 relative mRNA expression levels were detected with real - time quantitative polymerase chain reaction,respectively. Results Observation of green fluorescent protein ex-pression under a fluorescence microscope indicated similar transfection efficiencies,and miRNA - 30c knockdown re-leased the activity of target gene Gli2. As a result,miRNA - 30c knockdown vector was constructed successfully(P ﹤0. 001). During differentiation of mouse P19 cells into myocardial cells,the beating cell clusters in miRNA - 30c knockdown cells were much lower than those in the control cells,and cTnT,NKX2. 5,GATA4 in miRNA - 30c knock-down cells showed significantly lower expression than those in the control cells( all P ﹤ 0. 05). Conclusions miRNA - 30c inhibits the P19 cell proliferation and differentiation. This study gives us a new insight of heart develop-ment and we need more efforts on exploring the deep function of heart diseases.
ABSTRACT
Objective To observe the expression changes in microRNA (miR)-379 in the developmental process of the mouse heart and during the differentiation of P19 cells into cardiac myocytes,and to explore the possible relationship between miR-379 and the differentiation of cardiacmyocytes.Methods Heart tissues were collected from fetal mice in pregnant ones at their gestational age (8.5,11.5,14.5 and 18.5 days) respectively.Heart tissue sections of the fatal mice were obtained to observe the heart development process.Then total RNA was isolated from heart tissues by using the TRIzol method.Complementary DNA was synthesized from 1 μg total RNA by using a Reverse Transcriptase Kit.Finally,real-time PCR (RT-PCR) was employed to detect the expression of miR-379.At the same time,P19 cells were cultured with 10 mL/L Dimethyl sulfoxide in suspension for 4 days to form cell aggregation,and these aggregations were transferred into 6-wells plate for culturing by adherence.Beating cells were detected with microscopy on the 10th day after induction.Afterwards,total RNA was extracted from cultured P19 cells at different time points.Reverse transcription was executed to get DNA.At last,RT-PCR was used to explore the expression of miR-379 on 0,4,6,10 days after aggregation.Results The expression level of miR-379 was down-regulated gradually in the developing heart (at gestational age of 8.5,11.5,14.5,16.5 days,respectively),and there were significant differences on the different days (F =21.13,P < 0.05).On the other hand,myocardial markers of troponin T represented an increasing trend during the process of P19 cells induction,which demonstrated that P19 cells were successfully induced into cardiomyocyte-like cells.Meanwhile,miR-379 showed a low expression on day 0 of P19 cells aggregation.On day 4,miR-379 demonstrated a higher level.Afterwards,miR-379 proved to be down-regulated gradually.Conclusions miR-379 plays a role in the process of the heart development,but the specific mechanisms need further research.
ABSTRACT
The Human Milk Banking Association of North America(HMBANA) is a professional association for supporters of non-profit donor human milk banking.HMBANA develops guidelines for donor human milk banking practices.The construction of China's human milk bank has just begun in few areas in 2013.To further promote the development and implementation of donor human milk banking in our country,this review introduce the guideline for establishment and operation of a donor human milk bank which drafted by HMBANA in 2013.The guideline can provide the basis for the development of human milk bank in our country.