The variation of antenatal corticosteroids administration for the singleton preterm birth in China, 2017 to 2018.

BACKGROUND: The administration of antenatal corticosteroids (ACS) to women who are at risk of preterm birth has been proven to reduce not only the mortality, but also the major morbidities of the preterm infants. The rate of ACS and the risk factors associated with ACS use in Chinese population is unclear. This study aimed to investigate the rate of ACS use and the associated perinatal factors in the tertiary maternal centers of China. METHODS: Data for this retrospective observational study came from a clinical database of preterm infants established by REIN-EPIQ trial. All infants born at < 34 weeks of gestation and admitted to 18 tertiary maternal centers in China from 2017 to 2018 were enrolled. Any dose of dexamethasone was given prior to preterm delivery was recorded and the associated perinatal factors were analyzed. RESULTS: The rate of ACS exposure in this population was 71.2% (range 20.2 - 92%) and the ACS use in these 18 maternal centers varied from 20.2 to 92.0% in this period. ACS exposure was higher among women with preeclampsia, caesarean section delivery, antibiotic treatment and who delivered infants with lower gestational age and small for gestational age. ACS use was highest in the 28-31 weeks gestational age group, and lowest in the under 26 weeks of gestational age group (x2 = 65.478, P < 0.001). ACS exposure was associated with lower odds of bronchopulmonary dysplasia or death (OR, 0.778; 95% CI 0.661 to 0.916) and invasive respiration requirement (OR, 0.668; 95% CI 0.585 to 0.762) in this population. CONCLUSION: The ACS exposure was variable among maternity hospitals and quality improvement of ACS administration is warranted.

Effects of home and education environments on children's motor performance in China.

AIM: The aim of this study was to examine the effects of home and educational environments on children's motor performance in China. METHOD: We conducted a cross-sectional study of 4001 preschool children selected from 160 classes. The children's motor performance was assessed using the Movement Assessment Battery for Children, 2nd edition (MABC-2). Home and educational environments were evaluated using validated checklists. The effects of home and educational environments on motor performance were analysed using mixed and multilevel logistic regression models. RESULTS: The results showed that one score increase in the outside space of the family home was positively associated with the increase in total test score (0.104) subtest score of aiming and catching (0.037), and balance (0.034) of the MABC-2, after adjusting for potential confounders (each p<0.05). Possession of motor toys at home and parental rearing behaviours were also related to total test score, manual dexterity, and balance (ß=0.022-0.104, each p<0.05). Space and furnishings, activity, and interaction in the classroom had a significant positive association with total test score (ß=0.069-0.201), and with subtest scores of manual dexterity, aiming and catching, and balance respectively (ß=0.115-0.206). Space and furnishings of classrooms and possession of toys in the household were protective factors for 'at risk' or significant poor performance (odds ratio 0.942-0.973, each p<0.05). INTERPRETATION: A permissive and accepting family and educational environment made a positive contribution to children's motor performance. Access to sufficient space and furnishings within the classroom, as well as toys in the family, were protective factors for poor motor performance. Future assistance is needed to support an advantageous environment in early childhood programmes in China.

Histone deacetylase inhibitor sodium butyrate suppresses DNA double strand break repair induced by etoposide more effectively in MCF-7 cells than in HEK293 cells.

BACKGROUND: Histone deacetylase inhibitors (HDACi's) are emerging as promising anticancer drugs alone or in combination with chemotherapy or radiotherapy agents. Previous research suggests that HDACi's have a high degree of selectivity for killing cancer cells, but little is known regarding the impact of different cellular contexts on HDACi treatment. It is likely that the molecular mechanisms of HDACi's involve processes that depend on the chromatin template, such as DNA damage and repair. We sought to establish the connection between the HDACi sodium butyrate and DNA double-strand break (DSB) damage in human breast cancer MCF-7 and non-cancerous human embryonic kidney293 (HEK293) cells. RESULTS: Sodium butyrate inhibited the proliferation of both HEK293 and MCF-7 cells in a dose- and time- dependent manner, but the effects on MCF-7 cells were more obvious. This differential effect on cell growth was not explained by differences in cell cycle arrest, as sodium butyrate caused an arrest in G1/G2 phase and a decrease in S phase for both cell lines. At high doses of sodium butyrate or in combination with etoposide, MCF-7 cells formed fewer colonies than HEK293 cells. Furthermore, sodium butyrate enhanced the formation of etoposide-induced γ-H2AX foci to a greater extent in MCF-7 than in HEK293 cells. The two cells also displayed differential patterns in the nuclear expression of DNA DSB repair proteins, which could, in part, explain the cytotoxic effects of sodium butyrate. CONCLUSIONS: These studies suggest that sodium butyrate treatment leads to a different degree of chromatin relaxation in HEK293 and cancerous MCF-7 cells, which results in differential sensitivity to the toxic effects of etoposide in controlling damaged DNA repair.

Delivery room resuscitation intensity and associated neonatal outcomes of 24+0-31+6 weeks' preterm infants in China: a retrospective cross-sectional study.

BACKGROUND: The aim of this study was to review current delivery room (DR) resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24+0-31+6 weeks' gestation age (GA). METHODS: This was a retrospective cross-sectional study. The source population was infants born at 24+0-31+6 weeks' GA who were enrolled in the Chinese Neonatal Network 2019 cohort. Eligible infants were categorized into five groups: (1) regular care; (2) oxygen supplementation and/or continuous positive airway pressure (O2/CPAP); (3) mask ventilation; (4) endotracheal intubation; and (5) cardiopulmonary resuscitation (CPR). The association between DR resuscitation and short-term outcomes was evaluated by inverse propensity score-weighted logistic regression. RESULTS: Of 7939 infants included in this cohort, 2419 (30.5%) received regular care, 1994 (25.1%) received O2/CPAP, 1436 (18.1%) received mask ventilation, 1769 (22.3%) received endotracheal intubation, and 321 (4.0%) received CPR in the DR. Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation, and antenatal steroid use tended to be associated with a lower need for resuscitation (P < 0.001). Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal factors. Resuscitation strategies vary widely between centers, with over 50% of preterm infants in eight centers requiring higher intensity resuscitation. CONCLUSIONS: Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China. There is wide variation in resuscitative approaches across delivery centers, and ongoing quality improvement to standardize resuscitation practices is needed.

Postresuscitation cyclosporine treatment attenuates myocardial and cardiac mitochondrial injury in newborn piglets with asphyxia-reoxygenation.

OBJECTIVES: Cardiovascular dysfunction occurs in the majority of asphyxiated neonates and has been suggested to be a major cause of neonatal morbidity and mortality. We previously demonstrated that cyclosporine A treatment during resuscitation can significantly improve cardiovascular performance in asphyxiated newborn piglets. However, the mechanisms through which cyclosporine elicits its protective effect in neonates have not yet been fully characterized. We hypothesized that cyclosporine A treatment would attenuate myocardial and cardiac mitochondrial injury during the resuscitation of asphyxiated newborn piglets. DESIGN: After acute instrumentation, piglets received normocapnic alveolar hypoxia (10% to 15% oxygen) for 2 hours followed by reoxygenation with 100% oxygen (0.5 hr) and then 21% oxygen (3.5 hr). At 4 hours of reoxygenation, plasma troponin level, left ventricle myocardial levels of lipid hydroperoxides, cytochrome-c, and mitochondrial aconitase activity were determined. SETTING: Neonatal asphyxia and reoxygenation. SUBJECTS: Twenty-four newborn (1-4 days old) piglets. INTERVENTIONS: Piglets were randomized to receive an IV bolus of cyclosporine A (10 mg/kg) or normal saline (placebo, control) at 5 minutes of reoxygenation (n=8/group). Sham-operated piglets (n=8) underwent no asphyxia-reoxygenation. MEASUREMENTS AND MAIN RESULTS: Asphyxiated piglets treated with cyclosporine had lower plasma troponin and myocardial lipid hydroperoxides levels (vs. controls, both p<0.05, analysis of variance). Cyclosporine treatment also improved mitochondrial aconitase activity and attenuated the rise in cytosol cytochrome-c level (vs. controls, all p<0.05). The improved mitochondrial function significantly correlated with cardiac output (p<0.05, Spearman rank-correlation test). CONCLUSIONS: We demonstrate that the postresuscitation administration of cyclosporine attenuates myocardial and cardiac mitochondrial injury in asphyxiated newborn piglets following resuscitation.

Cyclosporine treatment improves cardiac function and systemic hemodynamics during resuscitation in a newborn piglet model of asphyxia: a dose-response study.

OBJECTIVES: Asphyxiated neonates often have myocardial depression, which is a significant cause of morbidity and mortality. Cardioprotective effects of cyclosporine have been observed in adult patients and animals with myocardial infarction. However, the cardioprotective effect of cyclosporine in neonates has not yet been studied. We hypothesize that cyclosporine will improve cardiac function and reduce myocardial injury in asphyxiated newborn piglets. DESIGN: Thirty-six piglets (1-4 days old, weighing 1.4-2.5 kg) were acutely instrumented for continuous monitoring of cardiac output and systemic arterial pressure. After stabilization, normocapnic alveolar hypoxia (10% to 15% oxygen) was instituted for 2 hrs followed by reoxygenation with 100% oxygen for 0.5 hrs and then 21% for 3.5 hrs. A nonasphyxiated, sham-operated group was included (n = 4) to control for effects of the surgical model. Plasma troponin and myocardial lactate concentrations were determined as well as morphologic examinations. SETTING: Neonatal asphyxia and reoxygenation. SUBJECTS: Newborn (1-4 days old) piglets. INTERVENTIONS: Piglets were block-randomized to receive intravenous boluses of cyclosporine A (2.5, 10, or 25 mg/kg) or normal saline (control) at 5 mins of reoxygenation (n = 8/group). MEASUREMENTS AND MAIN RESULTS: Cardiac index, heart rate, systemic oxygenation, plasma troponin, and left ventricular lactate were measured. Hypoxic piglets had cardiogenic shock (cardiac output 40% to 48% of baseline), hypotension (mean arterial pressure 27-31 mm Hg), and acidosis (pH 7.04). Cyclosporine treatment caused bell-shaped improvements in cardiac output, stroke volume, and systemic oxygen delivery (p < .05 vs. controls). Plasma troponin and left ventricle lactate were higher in controls than that of 2.5 and 10 mg/kg cyclosporine-treated groups (p < .05). Although histologic features of myocardial injury were not different among groups, severe damage was observed in mitochondria of control piglets but attenuated in that of cyclosporine (10 mg/kg) treatment. CONCLUSIONS: Postresuscitation administration of cyclosporine causes preservation of cardiac function and attenuates myocardial injury in newborn piglets after asphyxia-reoxygenation.

Hypoxia-ischemia upregulates TRAIL and TRAIL receptors in the immature rat brain.

The immature brain is susceptible to inflammatory injury induced by hypoxia-ischemia (HI) or infection, which causes serious neurodevelopmental disabilities in the survivors of preterm births. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (death receptor DR4/5 and decoy receptor DcR1/2) were reported to mediate various neuroinflammatory responses. However, little information is available regarding the role of TRAIL and its receptors in the immature brain after HI. The purpose of this study was to evaluate the expression of TRAIL and its receptors in the immature brain after HI and relate this expression to neurological function. We performed right common carotid artery ligation followed by hypoxia (6% O(2), 37°C) for 2.5 h to induce HI in postnatal day 3 rats. The distribution of TRAIL and its receptors, caspase-3 and CD68-labeled microglia/macrophages was evaluated 24 h after HI by immunostaining. The protein and mRNA expression of TRAIL and DR5 was measured by Western blot and real-time PCR, respectively. Delayed neuronal loss was evaluated by NeuN and Nissl staining 7 days after HI. Furthermore, neurological deficits were evaluated by a righting reflex test, time of eye opening and T-maze test. The expression of TRAIL, DR5 and DcR1/2 receptors and caspase-3 was more pronounced in the ipsilateral hemisphere compared with the contralateral part and the control group 24 h after HI. DR5/active caspase-3 double-positive cells were observed at 24 h after HI in the ipsilateral hemisphere but not in the contralateral hemisphere. The TRAIL and CD68 double-labeled cells were more pronounced in the ipsilateral cortical regions compared with the corresponding regions of the contralateral part. HI also resulted in a significant increase in TRAIL and DR5 protein and mRNA expression at 24 h, which corresponded to neuronal cell loss 7 days after HI. Furthermore, the HI group displayed impaired neurobehavioral development compared with the control group (p < 0.05). Altogether our results show that the TNF-α superfamily ligand TRAIL is induced on CD68+ microglia/macrophages after perinatal HI and that one of its receptors, DR5, is induced on neocortical neurons and glial cells. That many DR5+ cells were also caspase-3+ strongly supports the conclusion that these signaling molecules are involved in the delayed loss of neurons in the neocortex and in the neurobehavioral deficits that are often seen after perinatal HI.

Preparing PAMAM-NK4 nano complexes and examining their in vitro growth suppression effects in breast cancer.

BACKGROUND: This study sought to examine the suppression of the NK4 (which is a fragment that originates from the trypsin digestion of the hepatocyte growth factor) gene as mediated by new nano material polyamidoamine (PAMAM) dendrimers in the growth of breast cancer cells MDA-MB-231 and MCF-7, and the therapeutic effects in a nude mice model of transplanted tumor cell MDA-MB-231. METHODS: We built PAMAM-NK4 nano particles and detected the in vitro transfection rate. Nano complexes and blank plasmid PAMAM dendrimers were transfected to MDA-MB-231 and MCF-7 cells, respectively. The western-blotting method, MTT experiment method, and bead method were used to detect the effects of the nano complexes on NK4 protein expression, cell proliferation, and cell apoptosis. The nude mice model of transplanted tumor cell MDA-MB-231 comprised 40 nude female mice who were subject to injections. The mice were randomly divided into four groups, comprising 10 mice per group. The control, blank plasmid and treatment groups were subcutaneously injected with 0.2 mL of 0.9% NaCl (Sodium chloride) solution, 0.2 mL of plasmid solution (including 100 µg PAMAM pcDNA3.1(-) blank plasmid nano complexes) and 0.2 mL of plasmid solution (including PAMAM-NK4 100 µg) beside the tumor inoculation spot, respectively. The positive control group was intraperitoneally injected with 0.2 mL of doxorubicin solution, including 100 µg doxorubicin. Western blotting was used to detect the NK4 protein expression of the transplanted tumor tissues of the various groups. RESULTS: NK4 protein was successfully expressed in MDA-MB-231 and MCF-7 cells transfected with PAMAM-NK4 nano particles, and cell proliferation was suppressed and cell apoptosis was induced. The tumor volumes and masses of the treatment and positive control groups were obviously smaller than those of the control group. The differences were statistically significant (P<0.05). The treatment group had an obviously higher mean value of NK4 protein expression than the control group. The differences were statistically significant (P<0.05). CONCLUSIONS: PAMAM-NK4 nano complexes suppress the growth of the breast cancer cells MDA-MB-231 and MCF-7, and had a treatment effect on this tumor nude mice model of breast cancer cells.

Optimised retinopathy of prematurity screening guideline in China based on a 5-year cohort study.

PURPOSES: To develop an optimised retinopathy of prematurity (ROP) screening guideline by adjusting the screening schedule and thresholds of gestational age (GA) and birth weight (BW). METHODS: A multicentre retrospective cohort study was conducted based on data from four tertiary neonatal intensive care units in Shanghai, China. The medical records of enrolled infants, born from 2012 to 2016 who underwent ROP examinations, were collected and analysed. The incidence and risk factors for ROP were analysed in all infants. Postnatal age (PNA) and postmenstrual age (PMA) of infants, detected to diagnose ROP for the first time, were compared with the present examination schedule. The predictive performance of screening models was evaluated by internally validating sensitivity and specificity. RESULTS: Of the 5606 eligible infants, ROP was diagnosed in 892 (15.9%) infants; 63 (1.1%) of them received treatment. The mean GA of ROP patients was 29.4±2.4 weeks, and the mean BW was 1260±330 g. Greater prematurity was associated with an older PNA at which ROP developed. The minimum PMA and PNA at which diagnosis of treatable ROP occurred were 32.43 and 3 weeks, respectively. The optimised criteria (GA <32 weeks or BW <1600 g) correctly predicted 98.4% type 1 ROP infants, reducing the infants requiring examinations by 43.2% when internally validated. CONCLUSIONS: The incidence of type 1 ROP and the mean GA and BW of ROP infants have decreased in China. The suggested screening threshold and schedule may be reliably used to guide the modification of ROP screening guideline and decrease medical costs.

Mortality and Morbidity of Infants Born Extremely Preterm at Tertiary Medical Centers in China From 2010 to 2019.

Importance: Extreme prematurity is associated with a substantial burden on health care systems worldwide. However, little is known about the prognosis of infants born extremely preterm in developing countries, such as China. Objective: To describe survival and major morbidity among infants born extremely preterm in China over the past decade. Design, Setting, and Participants: This retrospective cohort study was conducted from January 1, 2010, through December 31, 2019. Included individuals were infants with gestational age less than 28 weeks discharged from 1 of 68 neonatal intensive care units located in 31 provinces in China. Data were analyzed from August through October 2020. Exposure: Extremely preterm birth. Main Outcomes and Measures: Survival to discharge and major morbidity (ie, bronchopulmonary dysplasia, grades III-IV intraventricular hemorrhage, white matter injury, stage II-III necrotizing enterocolitis, sepsis, or severe retinopathy of prematurity) were measured. Results: Among 8514 eligible infants, 5295 (62.2%) were male and 116 infants (2.0%) were small for gestational age (SGA). Overall, 5302 infants (62.3%) survived to discharge. The survival rate was 1 of 21 infants (4.8%) at 22 weeks, 13 of 71 infants (18.3%) at 23 weeks, 144 of 408 infants (35.3%) at 24 weeks, 480 of 987 infants (48.6%) at 25 weeks, 1423 of 2331 infants (61.0%) at 26 weeks, and 3241 of 4692 infants (69.1%) at 27 weeks. Survival increased from 136 of 241 infants (56.4%; 95% CI, 50.1%-62.7%) in 2010 to 1110 of 1633 infants (68.0%; 95% CI, 65.7%-70.2%) in 2019 for infants born at 24 to 27 weeks (mean difference, 11.5%; 95% CI, 4.9%-18.2%; P < .001), without a significant change for infants born at less than 24 weeks. Major morbidity was found in 5999 of 8281 infants overall, for a rate of 72.4%, which increased from 116 of 223 infants (52.0%; 95% CI, 45.4%-58.6%) to 1363 of 1656 infants (82.3%; 95% CI, 80.5%-84.1%) from 2010 to 2019 (mean difference, 30.3%; 95% CI, 23.5%-37.1%, P < .001). Regional variations in survival were identified, with an almost 2-fold increase (1.94-fold; 95% CI, 1.66-2.27; P < .001) from 188 of 474 infants (39.7%) in northwest China to 887 of 1153 infants (76.9%) in north China. Gestational age (adjusted risk ratio [aRR], 1.084; 95% CI, 1.063-1.105; P < .001), birth weight (aRR, 1.028; 95% CI, 1.020-1.036; P < .001), premature rupture of membranes (aRR, 1.025; 95% CI, 1.002-1.048; P = .03), and antenatal steroids (aRR, 1.029; 95% CI, 1.004-1.055; P = .02) were associated with improved survival, while being born SGA (aRR, 0.801; 95% CI, 0.679-0.945; P = .01), being male (aRR, 0.975; 95% CI, 0.954-0.997; P = .02), multiple birth (aRR, 0.955; 95% CI, 0.929-0.982; P = .001), having a mother with gestational diabetes (aRR, 0.946; 95% CI, 0.913-0.981; P = .002), and low Apgar score (aRR, 0.951; 95% CI, 0.925-0.977; P < .001) were found to be risk factors associated with decreased chances of survival. Conclusions and Relevance: This study found that infants born extremely preterm were at increased risk of mortality and morbidity in China, with a survival rate that improved over time and a major morbidity rate that increased. These findings suggest that more active and effective treatment strategies are needed, especially for infants born at gestational age 25 to 27 weeks.

Perinatal risk factors for pulmonary hemorrhage in extremely low-birth-weight infants.

BACKGROUND: Pulmonary hemorrhage (PH) is a life-threatening respiratory complication of extremely low-birth-weight infants (ELBWIs). However, the risk factors for PH are controversial. Therefore, the purpose of this study was to analyze the perinatal risk factors and short-term outcomes of PH in ELBWIs. METHODS: This was a retrospective cohort study of live born infants who had birth weights that were less than 1000 g, lived for at least 12 hours, and did not have major congenital anomalies. A logistic regression model was established to analyze the risk factors associated with PH. RESULTS: There were 168 ELBWIs born during this period. A total of 160 infants were included, and 30 infants were diagnosed with PH. Risk factors including gestational age, small for gestational age, intubation in the delivery room, surfactant in the delivery room, repeated use of surfactant, higher FiO2 during the first day, invasive ventilation during the first day and early onset sepsis (EOS) were associated with the occurrence of PH by univariate analysis. In the logistic regression model, EOS was found to be an independent risk factor for PH. The mortality and intraventricular hemorrhage rate of the group of ELBWIs with PH were significantly higher than those of the group of ELBWIs without PH. The rates of periventricular leukomalacia, moderate-to-severe bronchopulmonary dysplasia and severe retinopathy of prematurity, and the duration of the hospital stay were not significantly different between the PH and no-PH groups. CONCLUSIONS: Although PH did not extend hospital stay or increase the risk of bronchopulmonary dysplasia, it increased the mortality and intraventricular hemorrhage rate in ELBWIs. EOS was the independent risk factor for PH in ELBWIs.

Video Laryngoscopy Improves the Success of Neonatal Tracheal Intubation for Novices but Not for Experienced Medical Staff.

Background: There is limited evidence on the use of video laryngoscopy (VL) in neonatal tracheal intubation (NTI) during neonatal resuscitation. In this study, we aimed to compare the difference between direct laryngoscopy (DL) and VL in NTI of trainees during neonatal resuscitation training. Materials and Methods: A prospective observational study was conducted during a neonatal resuscitation training course to examine three circumstances: NTI by experienced medical staff (EMS) and less-experienced medical staff (LEMS) in a neonatal resuscitation scenario; NTI by EMS and LEMS with an ongoing chest compression; and NTI by midwives who were novices in the procedure. The trainees were given scenarios or were shown demonstrations on newborn simulation manikins and were required to perform an NTI on a simulation manikin using DL and/or VL. The mean intubation time and success rate of intubation were measured. Results: The mean NTI time for EMS using VL (24.1 ± 7.2 s) was significantly longer than that using DL intubation (18.1 ± 6.9 s, P < 0.001), whereas there was no significant difference between using VL and DL for LEMS. EMS spent slightly less time on NTI than did LEMS using both VL and DL, but there were no statistically significant differences (both p > 0.05). The NTI success rate for EMS using VL (48.0%, 12/25) was significantly lower than that using DL (88.0%, 22/25, P = 0.004), while the NTI success rate for LEMS using VL (68.2%, 15/22 vs. 40.9%, 9/22) was higher than that using DL, but there was no statistical significance. When NTI was required with ongoing chest compressions, there was no significant difference in the mean NTI time and success rate between using VL and DL for EMS or LEMS. In the group of midwives who were novices in NTI, after they watched a demonstration teaching NTI, the intubation time using VL (19.6 ± 9.0 s) was significantly shorter than that using DL (28.0 ± 6.7 s, P < 0.001). The success rate of NTI using VL was significantly higher (96.2%; 25/26) than that using DL (69.2%; 18/26). Conclusion: The video laryngoscopy could be an effective training tool for inexperienced staff in developing the skill of tracheal intubation.

A randomized controlled trial protocol comparing the feeds of fresh versus frozen mother's own milk for preterm infants in the NICU.

BACKGROUND: Necrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at < 30 weeks' gestation. The incidence of NEC is reduced when infants are fed human milk. However, in many neonatal intensive care units (NICUs), it is standard practice to freeze and/or pasteurize human milk, which deactivates bioactive components that may offer additional protective benefits. Indeed, our pilot study showed that one feed of fresh mother's own milk per day was safe, feasible, and can reduce morbidity in preterm infants. To further evaluate the benefits of fresh human milk in the NICU, a randomized controlled trial is needed. METHODS: Our prospective multicenter, double-blinded, randomized, controlled trial will include infants born at < 30 weeks' gestation and admitted to one of 29 tertiary NICUs in China. Infants in the intervention (fresh human milk) group (n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks' corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks' corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors. DISCUSSION: Our double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants. TRIAL REGISTRATION: Chinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019; http://www.chictr.org.cn/showprojen.aspx?proj=34276.

Sodium tanshinone IIA sulfonate increased intestinal hemodynamics without systemic circulatory changes in healthy newborn piglets.

In traditional Chinese medicine, tanshinone IIA is a lipid-soluble component of Danshen that has been widely used for various cardiovascular and cerebrovascular disorders, including neonatal asphyxia. Despite promising effects, little is known regarding the hemodynamic effects of tanshinone IIA in newborn subjects. To examine the dose-response effects of sodium tanshinone IIA sulfonate (STS) on systemic and regional hemodynamics and oxygen transport, 12 newborn piglets were anesthetized and acutely instrumented for the placement of femoral arterial and venous, pulmonary arterial catheters to measure mean arterial, central venous, and pulmonary arterial pressures, respectively. The blood flow at the common carotid, renal, pulmonary, and superior mesenteric (SMA) arteries were continuously monitored after treating the piglets with either STS (0.1-30 mg/kg iv) or saline treatment (n = 6/group). To further delineate the underlying mechanisms for vasorelaxant effects of STS, in vitro vascular myography was carried out to compare its effect on rat mesenteric and carotid arteries (n = 4-5/group). STS dose-dependently increased the SMA blood flow and the corresponding oxygen delivery with no significant effect on systemic and pulmonary, carotid and renal hemodynamic parameters. In vitro studies also demonstrated that STS selectively dilated rat mesenteric but not carotid arteries. Vasodilation in mesenteric arteries was inhibited by apamin and TRAM-34 (calcium-activated potassium channel inhibitors) but not by meclofenamate (cyclooxygenase inhibitor) or N-nitro-l-arginine methyl ester hydrochloride (nitric oxide synthase inhibitor). In summary, without significant hemodynamic effects on newborn piglets, intravenous infusion of STS selectively increased mesenteric perfusion in a dose-dependent manner, possibly via an endothelium-derived hyperpolarizing factor vasodilating pathway.

Comparing the Quality of Cardiopulmonary Resuscitation Performed at the Over-the-Head Position and Lateral Position of Neonatal Manikin.

Background: Recent neonatal resuscitation guidelines suggest to perform chest compression (CC) at over-the-head (OTH) position instead of lateral position when further interventions including umbilical venous access are needed. Little information is available regarding the quality of cardiopulmonary resuscitation at different positions. Our study compared the quality of CC and ventilation at OTH position vs. lateral position in simulated neonatal resuscitation. Methods: Thirty-nine neonatal practitioners who attended the NRP®-based Provider renewal course workshop participated this study. Laerdal QCPR infant model were used to collect the data (2-miutes continuous recording) on quality of CC and ventilation of all participants at OTH position and lateral position in randomized order, both coordinated with mask ventilation or endotracheal ventilation through a Neopuff© T-piece system. The quality of CC and ventilation were compared. Participants also reported their demographics and opinions in anonymous questionnaires after the session. Results: The quality of CC and ventilation was not different when CPR was performed at OTH position and lateral position, in both mask and endotracheal ventilation. When CPR was performed with endotracheal ventilation, there were small faster frequencies of CC and ventilation at OTH position, compared with those at lateral position (p = 0.004). Most participants (87%) liked the CC performed at OTH position and had no adverse feedback. Conclusions: Performing CC at OTH position was generally well-received in simulated resuscitation; the quality of CC and ventilation at OTH position was not significantly different from that at lateral position, irrespective of mask or endotracheal ventilation.

[Study on the effect of phloretin on inhibiting malignant pheotype of BEL-7402 cells].

OBJECTIVE: To investigate the effect of phloretin on inhibiting BEL-7402 cells' growth, invasive, migration and adhesion ability and the rate of colony formation. METHODS: BEL-7402 cells' growth, invasive, migration and adhesion ability and the rate of colony formation were examined with MIT method and Costar Transwell. RESULTS: Phloretin inhibited the growth, invasive, migration and adhesion ability of BEL-7402 cells and reduced the rate of colony formation in dose-dependent. CONCLUSION: Phloretin can inhibit BEL-7402 cells' malignant pheotype.

[Study on apoptosis of BEL-7402 cells induced by galangin].

OBJECTIVE: To investigate apoptosis of BEL-7402 cells induced by Galangin. METHODS: Cytotoxicity and cell viability were assayed by MT methods. Morphologic assessment of apoptosis was performed by fluorescence microscope, cell cycle and mitochondrial membrane potential were analyzed by flow cytometry, Caspases Activities were detected by chromogenic substrate assay. RESULTS: BEL-7402 cells treated with Galangin showed apparently cytotoxicity, IC50 of Galangin was 30.15 mg/L The growth curve showed that the ratio of growth decreased with the increasing of concentration of Galangin. The apoptosis appeared 24 hours after treated with 20-80 mg/L Galangin, morphologic changes included nuclear chromatin condensation and fluorescence strength was observed with fluorescence microscope. The activity of Caspase-9 attained to peak value at 6 h, while Caspase-6 activity was up to peak value at 12h and Caspase-3 activity attained to peak value at 18 h. CONCLUSION: Galangin may induce BEL-7402 cells apoptosis by mitochondrial pathway.

Improvement of Expressed Breast Milk in Mothers of Preterm Infants by Recording Breast Milk Pumping Diaries in a Neonatal Center in China.

OBJECTIVES: Because inadequate expression of human milk (EBM) in mothers of hospitalized infants were noticed in a neonatal center of our hospital, family education program was carried out to increase the EBM. METHODS: A breast milk pumping diary was introduced to the mothers with preterm infant(s) admitted in the NICU. The ratios of EBM (days of EBM to NICU/hospitalized days), breast milk feeding (BMF) (days of infants fed with exclusive human milk/hospitalized days), mixed feeding (MF) (days of infants fed with partial breast milk and partial formula/hospitalized days), and formula feeding (FF) (days of infants fed with preterm formula/hospitalized days) were evaluated. RESULTS: During January to April, 2014, the ratios of EBM to the NICU, BMF, MF and FF were 28.11%, 6.6%, 32.8% and 60.6%, respectively. After the introduction of breast milk pumping diary to the mothers from May 2014, the ratio of EBM to the NICU increased significantly to 53.3% (p<0.01) within the following eight months. Both the ratios of BMF and MF also rose to 23.8% and MF 55.3%, respectively. Consequently, the ratio of FF was reduced to 20.9%. Exclusive breast milk feeding also significantly reduce the duration of nil per oral (NPO) of the very low birth weight infants during hospital stay as compared to those fed with mixed feeding and formula feeding. CONCLUSION: The introduction of a breast milk pumping diary was associated with a significant increase in the intake of EBM of the hospitalized preterm newborns.

The reliability and validity of the Developmental Coordination Disorder Questionnaire'07 for children aged 4-6 years in mainland China.

An effective population-based screening tool is needed to identify possible cases of Developmental Coordination Disorder (DCD) among preschool children in mainland China. We examined the psychometric properties of the DCD questionnaire'07 (DCDQ'07) in Chinese children aged 4-6. A total of 3316 children from 10 nursery schools were involved in the study. Internal consistency and test-retest reliability of the DCDQ'07 were estimated using Cronbach's alpha, item-total correlation and intraclass correlation co-efficient (ICC). The construct validity was evaluated using the exploratory and confirmatory factor analysis. Receiver operating characteristic (ROC) analysis was used to measure the accuracy of the DCDQ'07. The results showed that both internal consistency (Cronbach's alpha value of all items were above 0.85) and test-retest reliability (ICCs of 13 items and subscales were above 0.9) were excellent. Confirmatory factor analysis showed that each goodness-of-fit indices of the 3-factor model was above 0.9, indicating a satisfactory fit of the data to the model. Area under the ROC curve was comparatively small (0.641). With the exception of construct validity in younger children (4 years old) and discriminative validity, the Chinese version of the DCDQ'07 achieves satisfactory reliability and construct validity in mainland China. Nevertheless, the questionnaire should be not used in younger children, and further studies are needed to explore the use of Little DCD-Q in Chinese preschool children.

Infusing sodium bicarbonate suppresses hydrogen peroxide accumulation and superoxide dismutase activity in hypoxic-reoxygenated newborn piglets.

BACKGROUND: The effectiveness of sodium bicarbonate (SB) has recently been questioned although it is often used to correct metabolic acidosis of neonates. The aim of the present study was to examine its effect on hemodynamic changes and hydrogen peroxide (H(2)O(2)) generation in the resuscitation of hypoxic newborn animals with severe acidosis. METHODS: Newborn piglets were block-randomized into a sham-operated control group without hypoxia (n = 6) and two hypoxia-reoxygenation groups (2 h normocapnic alveolar hypoxia followed by 4 h room-air reoxygenation, n = 8/group). At 10 min after reoxygenation, piglets were given either i.v. SB (2 mEq/kg), or saline (hypoxia-reoxygenation controls) in a blinded, randomized fashion. Hemodynamic data and blood gas were collected at specific time points and cerebral cortical H(2)O(2) production was continuously monitored throughout experimental period. Plasma superoxide dismutase and catalase and brain tissue glutathione, superoxide dismutase, catalase, nitrotyrosine and lactate levels were assayed. RESULTS: Two hours of normocapnic alveolar hypoxia caused cardiogenic shock with metabolic acidosis (PH: 6.99 ± 0.07, HCO(3)(-): 8.5 ± 1.6 mmol/L). Upon resuscitation, systemic hemodynamics immediately recovered and then gradually deteriorated with normalization of acid-base imbalance over 4 h of reoxygenation. SB administration significantly enhanced the recovery of both pH and HCO(3-) recovery within the first hour of reoxygenation but did not cause any significant effect in the acid-base at 4 h of reoxygenation and the temporal hemodynamic changes. SB administration significantly suppressed the increase in H(2)O(2) accumulation in the brain with inhibition of superoxide dismutase, but not catalase, activity during hypoxia-reoxygenation as compared to those of saline-treated controls. CONCLUSIONS: Despite enhancing the normalization of acid-base imbalance, SB administration during resuscitation did not provide any beneficial effects on hemodynamic recovery in asphyxiated newborn piglets. SB treatment also reduced the H(2)O(2) accumulation in the cerebral cortex without significant effects on oxidative stress markers presumably by suppressing superoxide dismutase but not catalase activity.