Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Atmospheric Wet Iron, Molybdenum, and Vanadium Deposition in Chinese Terrestrial Ecosystems.

Iron (Fe), molybdenum (Mo), and vanadium (V) are the main components of the three known biological nitrogenases, which constrain nitrogen fixation and affect ecosystem productivity. Atmospheric deposition is an important pathway of these trace metals into ecosystems. Here, we explored the deposition flux, spatiotemporal pattern, and influencing factors of atmospheric wet Fe, Mo, and V deposition based on China Wet Deposition Observation Network (ChinaWD) data from 2016 to 2020. Our results showed that atmospheric wet Fe, Mo, and V deposition was 7.77 ± 7.24, 0.16 ± 0.11, and 0.13 ± 0.12 mg m-2 a-1 in Chinese terrestrial ecosystems, respectively, and revealed obvious spatial patterns but no significant annual trends. Wet Fe deposition was significantly correlated with the soil Fe content. Mo and V deposition was more affected by anthropogenic activities than Fe deposition. Wet Mo deposition was significantly affected by Mo ore reserves and waste incineration. V deposition was significantly correlated with domestic biomass burning. This study quantified wet Fe, Mo, and V deposition in China for the first time, and the implications of atmospheric trace metal deposition on biological nitrogen fixation were discussed.

N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker of Bronchopulmonary Dysplasia or Death in Preterm Infants: A Retrospective Cohort Analysis.

Objectives: To investigate the association between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) level on the first day of life and a composite outcome of bronchopulmonary dysplasia (BPD) or death in a cohort of infants born before 32 weeks of gestation. Methods: We retrospectively identified infants born before 32 weeks of gestation who had serum NT-proBNP levels measured when they were admitted to the Neonatal Intensive Care Unit shortly after birth. The outcome of BPD or death was assessed at 36 weeks of postmenstrual age. The association of serum NT-proBNP levels with BPD or death was evaluated. Receiver operator characteristic (ROC) curve analysis was used to evaluate the predictive performance of serum NT-proBNP levels. Results: A 100 and 47 preterm infants had serum NT-proBNP levels measured on the first day of life. Serum NT-proBNP level was significantly higher in preterm infants who developed moderate/severe BPD or died [3,855 (2,567-6,369) vs. 1,259 (950-2,035) in control infants, P < 0.001]. On binary regression analysis, a high natural logarithm of serum NT-proBNP levels was associated with increased risk of moderate/severe BPD or death adjusted for gestational age, birth weight, birth weight z-score, and Apgar scores at 1 and 5 min (odds ratio [OR] = 5.195, 95% confidence interval [CI] 2.667-10.117, P < 0.001). ROC analysis identified a NT-proBNP level of 2002.5 pg/mL to have 87.5% sensitivity and 74.7% specificity for predicting moderate/severe BPD or death. The area under the curve (AUC) was 0.853 (95% CI 0.792-0.914). Conclusion: Serum NT-proBNP level measured on the first day of life is a promising biomarker for predicting the development of moderate/severe BPD or death in preterm infants. Our findings warrant a larger prospective study to incorporate measurement of NT-proBNP in prognosticating outcomes in very preterm infants.

Heavy metal deposition through rainfall in Chinese natural terrestrial ecosystems: Evidences from national-scale network monitoring.

Industrialization and urbanization have led to increasingly serious levels of atmospheric heavy metal pollution, which is one of the main sources of heavy metals to terrestrial ecosystems. Therefore, it is essential to quantify atmospheric fluxes and explore their potential effects on natural ecosystems and human welfare. We monitored water-soluble heavy metals (lead (Pb), cadmium (Cd), and chromium (Cr)) in rainfalls on a monthly basis in 2013 and 2014, at 31 field stations located in typical natural Chinese ecosystems. The average soluble Pb, Cd, and Cr deposition was 1.90 ± 1.54, 0.28 ± 0.25, and 0.96 ± 0.48 mg m-2 yr-1, respectively, with a large variation among the different sites. Generally, the atmospheric deposition of soluble Pb, Cd, and Cr was higher in the southwest, central, south, and north China than in the northwest and northeast China, Inner Mongolia, and Qinghai-Tibet. As expected, the atmospheric heavy soluble metal deposition fluxes were significantly correlated with the number of vehicles (Ps < 0.1). The wet deposition of soluble Pb and Cr was positively correlated with oil and coal consumption, unlike Cd deposition. Moreover, soluble Pb and Cd in atmospheric wet deposition were positively correlated with the contents of Pb and Cd in soil at different regions. In this study, atmospheric heavy metal deposition through rainfall in typical natural ecosystems in China is assessed at the national scale, alerting potential ecological hazards resulting from an increasing atmospheric heavy metal deposition and providing a basis for future studies.

Interleukin-10 blocks in vitro replication of human cytomegalovirus by inhibiting the virus-induced autophagy in MRC5 cells.

BACKGROUND: Interleukin-10 is an important cytokine that regulates immune response. Previous studies have shown that human cytomegalovirus can trigger cell autophagy during the early stages of infection. To our knowledge, whether IL-10 inhibits HCMV-induced autophagy and virus replication has not been studied previously. OBJECTIVES: We investigated whether IL-10 affects cell viability and autophagy under the conditions of starvation and HCMV infection by using the MRC5 cell line. We also explored the role of IL-10-mediated autophagy on HCMV replication. RESULTS: Our data showed that IL-10 inhibited the autophagic flux of the MRC5 cells irrespective of starvation or HCMV infection, and suppressed HCMV replication. The promotion of autophagy with either a pharmacological inducer (rapamycin), or a technique to over-express the BECN1 gene reversed the effect of IL-10 on virus replication. Furthermore, the PI3K/Akt signal pathway was activated when the cells were pretreated with IL-10. CONCLUSIONS: Our results indicated that IL-10 can suppress HCMV replication by inhibiting autophagy in host cells during the early stages of infection.

Lipopolysaccharide induces up-regulation of TGF-α through HDAC2 in a rat model of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased alveolar number and increased airspace. Previous studies suggested that transforming growth factor-α (TGF-α) may contribute to arrested alveolar development in BPD. Histone deacetylases (HDACs) control cellular signaling and gene expression. HDAC2 is crucial for suppression of inflammatory gene expression. Here we investigated whether HDAC2 was involved in the arrest of alveolarization, as well as the ability of HDAC2 to regulate TGF-α expression in a rat model of BPD induced by intra-amniotic injection of lipopolysaccharide (LPS). Results showed that LPS exposure led to a suppression of both HDAC1 and HDAC2 expression and activity, induced TGF-α expression, and disrupted alveolar morphology. Mechanistic studies showed that overexpression of HDAC2, but not HDAC1, suppressed LPS-induced TGF-α expression. Moreover, the HDAC inhibitor TSA or downregulation of HDAC2 by siRNA both significantly increased TGF-α expression in cultured myofibroblasts. Finally, preservation of HDAC activity by theophylline treatment improved alveolar development and attenuated TGF-α release. Together, these findings indicate that attenuation of TGF-α-mediated effects in the lung by enhancing HDAC2 may have a therapeutic effect on treating BPD.

Screening for retinopathy of prematurity in China: a neonatal units-based prospective study.

PURPOSE: To analyze the incidence and severity of retinopathy of prematurity (ROP) in China, and to explore the workload implications of applying different criteria. METHODS: A prospective, neonatal units-based study undertaken in two tertiary level hospitals in Shanghai, China, from January 1, 2010 to December 31, 2012. All infants with birth weight (BW) of 2000 g or less and/or gestational age (GA) of 34 weeks or less were screened for ROP. Retinopathy of prematurity was classified using the international classification, and was treated in accordance with the recommendations of the Early Treatment for Retinopathy of Prematurity Cooperative Group. RESULTS: A total of 2825 (93.7%) of 3014 eligible infants were screened, and ROP was diagnosed in 503 infants (17.8%). One hundred ninety-one infants (6.8%) had type 1 or worse ROP and were treated with laser or vitrectomy. The mean GA of ROP patients was 29.9 ± 2.1 weeks and their mean BW was 1425 ± 266 g. Infants who needed treatment for ROP had a mean GA of 29.3 ± 2.1 weeks and mean BW of 1331 ± 330 g. Among these treated infants, 18 infants (9.4%) exceeded the United Kingdom's (UK) screening criteria, and 28 (14.7%) exceeded the criteria used in the United States (US). If narrower criteria, as in GA less than or equal to 33 weeks and/or BW less than or equal to 1750 g were adopted, almost 16.9% fewer infants would not have been examined, with no infant missing treatment. CONCLUSIONS: Larger, older infants are at risk in China and screening criteria used in the US and UK may not be suitable for China. Further population-based studies are recommended to determine the necessity of modifying the current ROP screening protocol.

Correlations of circulating peptide YY and ghrelin with body weight, rate of weight gain, and time required to achieve the recommended daily intake in preterm infants

The objective was to elucidate the relationships between serum concentrations of the gut hormone peptide YY (PYY) and ghrelin and growth development in infants for potential application to the clinical observation index. Serum concentrations of PYY and ghrelin were measured using radioimmunoassay from samples collected at the clinic. For each patient, gestational age, birth weight, time required to return to birth weight, rate of weight gain, time required to achieve recommended daily intake (RDI) standards, time required for full-gastric feeding, duration of hospitalization, and time of administration of total parenteral nutrition were recorded. Serum PYY and ghrelin concentrations were significantly higher in the preterm group (N = 20) than in the full-term group (N = 20; P < 0.01). Within the preterm infant group, the serum concentrations of PYY and ghrelin on postnatal day (PND) 7 (ghrelin = 1485.38 ± 409.24; PYY = 812.37 ± 153.77 ng/L) were significantly higher than on PND 1 (ghrelin = 956.85 ± 223.09; PYY = 545.27 ± 204.51 ng/L) or PND 3 (ghrelin = 1108.44 ± 351.36; PYY = 628.96 ± 235.63 ng/L; P < 0.01). Both serum PYY and ghrelin concentrations were negatively correlated with body weight, and the degree of correlation varied with age. Serum ghrelin concentration correlated negatively with birth weight and positively with the time required to achieve RDI (P < 0.05). In conclusion, serum PYY and ghrelin concentrations reflect a negative energy balance, predict postnatal growth, and enable compensation. Further studies are required to elucidate the precise concentration and roles of PYY and ghrelin in newborns and to determine the usefulness of measuring these hormones in clinical practice.

Hyperoxia arrests alveolar development through suppression of histone deacetylases in neonatal rats.

Bronchopulmonary dysplasia (BPD) poses a significant global health problem. It mainly occurs in preterm infants. It is histopathologically characterized by fewer and larger alveoli and less secondary septa, suggesting an arrested or disordered lung development. To date, the mechanisms that lead to the pathophysiological changes in BPD have still not been totally understood. In embryonic development, histone deacetylase (HDAC) plays an important role by regulating gene transcription. Here, we hypothesize that a decreased HDAC expression and activity, caused by preterm birth or environmental stresses, contribute to a disorder in alveolar development in BPD. To this end, newborn Sprague-Dawley rats subjected to hyperoxia (85% O(2) ) were used to investigate the gene expression and protein activity of HDAC and alveolar development in lungs. Our results showed that hyperoxia exposure led to a suppression of the HDAC1/HDAC2 expression and activity, and the overall HDAC activity, as well as arrest of alveolarization, and an elevated expression of the cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the lungs of newborn rats. However, preservation of HDAC activity by theophylline significantly improved alveolar development and attenuated CINC-1 release, all of which were blocked by a specific HDAC inhibitor, trichostatin A (TSA). TSA alone can disturb the alveolar development in neonatal rats. Our findings indicate that a persistent exposure to hyperoxia leads to a suppressed HDAC activity, which causes disorders in pulmonary development. This effect may be mediated by CINC-1. Attenuation of CINC-1-mediated inflammation by activating HDAC may have a protective effect in BPD.

Suppressive effects of intravenous immunoglobulin (IVIG) on human umbilical cord blood immune cells.

We investigated in vitro immunomodulatory effects of intravenous immunoglobulin (IVIG) on cord blood mononuclear cells (CBMNC), macrophages, dendritic cells and CD3(+) T cells were isolated from umbilical venous blood. Cell proliferation used (3)H-TdR incorporation, culture supernatants were assayed for cytokines using ELISA, and surface marker expressions were determined by flow cytometry. IVIG suppressed CBMNCs and CD3(+) T-cells proliferation, secretions of IL-10, INF-γ and TGF-ß(1), but not IL-4, and PHA-induced expressions of surface molecules (CD25, CD45RA and CD45RO), with more pronounced effects for CBMNCs. IVIG decreased cord blood (CB) macrophage phagocytosis and CD14, HLA-DR and CD86 expressions. IVIG increased CD14 expression and decreased MCH II expression for differentiation-stage CB dendritic cells (DCs) and increased CD14 expression and decreased CD80 and CD83 expressions of mature DCs, suggesting that IVIG intervention inhibited DC differentiation and maturation. In addition to T cells, IVIG immunomodulatory effects on CBMNCs involve a variety of cells and molecules. CB macrophages and CBMNC-DCs are targets of IVIG.

[Effects of hyperoxia on lung vascular development and expression of angiopoietin-1 in neonatal rat lungs].

OBJECTIVE: To study the effects of prolonged 85% oxygen exposure on lung vascular development and the expression of angiopoietin-1 (Ang-1) in the neonatal rat lungs. METHODS: Ninety-six Sprague-Dawley rat pups were randomly exposed to air (control group) and 85% oxygen (experimental group) 6 hrs after birth. The rats were sacrificed 3, 7 and 14 days after exposure and their lungs were sampled. The lung sections were stained with hematoxylin and eosin for histological evaluation and analysis of vessel volume density. Expressions of angiopoietin-1 (Ang-1) in lung tissue were measured by immunohistochemistry. Expression of Ang-1 protein and mRNA was detected by Western Blot and Real time-PCR. RESULTS: After being exposed to 85% oxygen for 14 days, lung tissues had pathological changes as "new" bronchopulmonary dysplasia (BPD). The RAC on day 7 and day 14 in experimental group decreased significantly as compared with the control group [(10.55 ± 0.13) vs. (11.74 ± 0.19), (12.47 ± 0.05) vs. (15.03 ± 0.16), P < 0.05]. The X-ray showed that the diameter of lung vessel was much smaller and the vessels had less branches in experimental group compared with the control group on day 14. The vessel volume density on day 14 in experimental group decreased significantly as compared with the control group [(3.55 ± 0.09) vs. (6.03 ± 0.16), P < 0.05]. Immunohistochemistry and Western blotting showed that the expressions of Ang-1 protein on day 7 and day 14 in the experimental group decreased significantly as compared with the control group [(4.27 ± 0.34) vs. (3.10 ± 0.29), P < 0.05, (5.65 ± 0.49) vs. (3.21 ± 0.28), P < 0.01], [(0.88 ± 0.31) vs. (0.41 ± 0.12), P < 0.05, (0.90 ± 0.29) vs. (0.21 ± 0.06), P < 0.01]. The expressions of Ang-1 mRNA on day 7 and day 14 in the experimental group also decreased significantly as compared with the control group [(0.85 ± 0.14) vs. (0.44 ± 0.21), P < 0.05, (0.87 ± 0.24) vs. (0.24 ± 0.05), P < 0.01]. CONCLUSIONS: Prolonged exposure of high concentration of oxygen may cause impairment of lung vascular development by inhibiting expression of Ang-1 in neonatal rats, which is likely to contribute to pathogenesis of BPD.

[Combined use of tandem mass spectrometry with urine gas chromatography/mass spectrometry is useful for diagnosis of inborn errors of metabolism in children].

OBJECTIVE: Many inborn errors of metabolism have similar presenting clinical manifestations, making early diagnosis difficult. We report our experience with tandem mass spectrometry combined with urine gas chromatography/mass spectrometry as a means of definitively diagnosing inborn errors of metabolism. METHODS: One hundred and thirty-two children with suspected inborn errors of metabolism but without specific clinical manifestations, admitted to the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between June 1, 2003 and September 30, 2006, were studied. Children received routine biochemical examinations, as well as mass spectrometry and gas chromatography-mass spectrometry. RESULTS: Fifteen cases (11.5%) were confirmed as having inborn errors of metabolism, including 6 cases of methylmalonic acidemia, 2 of propionic academia, 2 of Type II citrullinemia, 1 of biotinidase deficiency, 1 of tyrosinemia, 1 of maple syrup urine disease, 1 of omithine transcarbamylase deficiency and 1 of very long chain Acyl CoA dehydrogenase deficiency. CONCLUSIONS: The combined use of tandem mass spectrometry with urine gas chromatography mass spectrometry is useful for early diagnosis of inborn errors of metabolism in children with suspected inborn errors of metabolism but without specific clinical manifestations.

[Effects of nuclear factor-kappaB on ventilator induced lung biotrauma by higher tidal volume and its interaction with pro-inflammatory cytokines].

OBJECTIVES: To investigate the changes of nuclear factor (NF)-kappaB activation in lung tissues and expression of cytokines in homogenate from lung tissues in infant rabbits with mechanical ventilation (MV) caused lung injury. METHODS: Forty-five general grade healthy infant rabbits were randomly divided into 3 groups: (1) CONTROL: with no MV (NMV, n = 9); (2): Conventional MV (CMV, n = 9): V(T) = 8 ml/kg; (3): MV with large tidal volume (V(T)) (LMV, n = 9), V(T) = 24 ml/kg. NF-kappaB activity in nuclear protein from lung tissues was measured with electrophoretic mobility shift assay (EMSA); quantity of IkappaBalpha in cellular plasma from lung tissues was analyzed with Western blotting method; TNF-alpha and IL-8 mRNA and their concentrations in homogenate were measured from lung tissues with RT-PCR and ELISA, respectively. RESULTS: At all time points NF-kappaB activity was higher in LMV than that in CMV and NMV groups (P < 0.01). Quantity of IkappaBalpha decreased progressively in LMV with time (P < 0.01) as compared to CMV and NMV. The expressions of TNF-alpha and IL-8 and their protein quantity in lung tissues significantly increased in LMV after ventilation compared to that in CMV and NMV (P < 0.01). The expression level of TNF-alpha reached its peak at 4 hrs and IL-8 at 6 hrs after ventilation then TNF-alpha decreased significantly at 6 hrs after ventilation. Pathological examination of the lung tissues showed that as MV extended over the time in LMV, alveolar structures were severely destroyed and large number of WBC infiltrated in both alveolar sacs and pulmonary interstitia with RBC leakage. However, there was less lung injury in CMV and no obvious injury in NMV. CONCLUSIONS: IkappaBalpha degradation and NF-kappaB activation were involved in modulating the expression of pro-inflammatory cytokines in lung tissues during the occurrence of lung injury caused by injuring MV.