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Objective:To study the correlation of bone metabolism biomarkers between newborn twins and their mothers during pregnancy.Methods:From January 1, 2018 to June 30, 2022, newborn twins with mild symptoms admitted to the neonatal department of our hospital were retrospectively reviewed. The clinical data of the twins and their mothers were collected, including bone metabolism biomarkers of the twins within 3 d after birth and their mothers within last month during pregnancy. The twins were assigned into different groups according to gestational age(GA), birth weight(BW), the relationship between BW and GA(appropriate for GA(AGA),small for GA(SGA) and large for GA(LGA), birth season, gender, and the mothers' age, ethnicity, pre-delivery body mass index (BMI), gestational BMI increase, number of births and chorionic properties. The correlations of bone metabolism biomarkers between the twins and their mothers were analyzed.Results:A total of 302 pairs of twins were included. The incidence of insufficient or deficient serum 25-(OH)D 3 was 97.4% among the mothers, and 87.7% among the twins. The levels of blood phosphorus ( r=0.262, P<0.001) and 25-(OH)D 3 ( r=0.239, P=0.002) in mothers were positively correlated with the twin with larger BW. No significant differences existed in 25-(OH)D 3 between genders, AGA,SGA and LGA, birth season, and mothers' age, ethnicity, pre-delivery BMI, gestational BMI increase and chorionic properties( P>0.05). 25-(OH)D 3 in the twins were positively correlated with BW and 25-(OH)D 3 of mothers before delivery ( P<0.05) and negatively correlated with number of births ( P<0.05). Conclusions:In most mothers and their newborn twins, 25-(OH)D 3 are insufficient or deficient. The levels of blood phosphorus and 25-(OH) D 3 are correlated between the newborns and their mothers. The lower the BW of the newborn, the more times the mother give birth and the lower the mother's pre-delivery 25-(OH)D 3 level, the lower the newborn's 25-(OH)D 3 level.
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Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.
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Objective:To explore the effect of PSD-95 inhibitor ZL006 in neonatal rats with hypoxic-ischemic brain damage(HIBD) and its potential mechanism.Methods:The seven-day-old healthy Wistar rats( n=80) were randomly divided into control group( n=20), sham operation group( n=20) and operation group (HIBD model group, n=40). The operation group was randomly divided into ZL006, treatment group (intraperitoneal injection of ZL006, 10 mg/kg, n=20) and non-treatment group ( n=20). The neonatal rats of each group were randomly selected on the 1st and 7th day after operation, and the degree of cerebral infarction was observed by triphenyl tetrazolium chloride staining.The protein expression level of brain tissue in the injured area was examed by Western blot, and the effects of ZL006 on oxidative stress and antioxidant enzymes in rats with HIBD were evaluated by ELISA. Results:(1) On the first day after operation, the brain injury was the most serious in the non-treatment group, and the cerebral infarction decreased in the ZL006 treatment group.On the 7th day after operation, a little infarction could be seen in the operation group, but there was no significant difference among other three groups.(2)On the first day after operation, the expression of PSD-95 protein in the operation group was significantly higher than that in the control group and sham operation group( P<0.01). There was significant difference in the expression of PSD-95 protein between the ZL006 treatment group and the non-treatment group ( P<0.05). On the 7th day after operation, there was no significant difference in the expression of PSD-95 protein among three groups.(3)On the first day after operation, the expression of 4-hydroxynonenal in the operation group was significantly higher than that in the control group and sham operation group( P<0.01), and that in the non-treatment group was higher than that in the ZL006 treatment group ( P<0.05). On the 7th day after operation, there was no significant difference in the expression of 4-hydroxynonenal among three groups.(4) On the first day after operation, the expression of superoxide dismutase in the operation group was significantly lower than that in the control group and sham operation group( P<0.01), and that in the non-treatment group was lower than that in the ZL006 treatment group ( P<0.05). There was no significant difference in the expression level of superoxide dismutase among three groups on the 7th day after operation. Conclusion:It is suggested that PSD-95 may be involved in the early pathogenesis of HIBD, and ZL006 may have neuroprotective effect on HIBD in newborn rats.
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Objective To explore the relationship between serum glial fibrillary acidic protein (GFAP) level and neonatal hypoxic-ischemic encephalopathy (HIE),and to verify whether GFAP combined with craniocerebral magnetic resonance imaging (MRI) can more accurately evaluate the prognosis of HIE.Methods We selected HIE children who hospitalized in the department of neonatology,the affiliated hospital of Inner Mongolia Medical University from January 2017 to December 2017,and full-term newborns without brain injury who were hospitalized in the same period.Serum samples were taken for GFAP detection on the 1st,3rd,7th day after birth of HIE and the 3rd day after birth of full-term newborns without brain injury.All the subjects completed craniocerebral MRI examination and followed up.At the same time,the correlation between GFAP level and the severity of brain MRI was evaluated.Results (1) The level of serum GFAP in HIE group on the 3rd day after birth [(5.54 ± 1.30)ng/ml] was significantly higher than that in control group [(3.38 ± 0.31) ng/ml] (P ＜ 0.01).(2) Comparison of serum GFAP levels in HIE children with different degrees:the serum levels of GFAP in the severe group on the 1st,3rd and 7th day were as follows:(5.56 ± 1.89) ng/ml,(6.42 ± 1.63) ng/ml,(7.22 ± 1.30) ng/ml;the serum levels of GFAP in moderate group on the 1st,3rd and 7th day were as follows:(5.07 ±0.62)ng/ml,(6.73 ±0.772) ng/ml,(6.25 ±0.812)ng/ml;the serum levels of GFAP in mild group on the 1st,3rd and 7th day were as follows:(4.20 ±-0.13) ng/ml,(5.34 ±0.33) ng/ml,(4.52 ±0.33) ng/ml;the serum GFAP levels in severe group were higher than those in moderate group and mild group on the 1st,3rd and 7th day,and those in moderate group were higher than those in mild group (P ＜ 0.01).(3) Comparison of serum GFAP levels between sequelae group and non-sequelae group:there was no significant difference between sequelae group [(5.22 ± 1.52) ng/ml,(6.48 ± 1.17) ng/ml] and non-sequelae group [(4.47 ± 0.50)ng/ml,(5.75 ±0.88) ng/ml] on the 1st and 3rd day (P ＞0.05);there was significant difference between sequelae group [(6.93 ± 1.29) ng/ml] and non-sequelae group [(4.91 ± 0.77) ng/ml] on the 7th day (P ＜0.01).(4) Comparison of serum GFAP levels between abnormal group of MRI and normal group of MRI:the levels of serum GFAP on day 1,3 and 7 in abnormal craniocerebral MRI group were as follows:(5.25 ± 1.28) ng/ml,(6.66 ± 1.10) ng/ml,(6.64 ± 1.08) ng/ml;the levels of serum GFAP on day 1,3 and7 in the normal group of MRI were as follows:(4.26 ±0.25)ng/ml,(5.41 ±0.40) ng,/ml,(4.62 ±0.48) ng/ml;the serum levels of GFAP on day 1,3 and 7 in mild abnormal craniocerebral MRI group were as follows:(4.92 ±0.9)ng/ml,(6.42 ±0.47)ng/ml,(5.95 ±0.58)ng/ml;the levels of serum GFAP on day 1,3 and 7 in moderate abnormal group of craniocerebral MRI were as follows:(4.49 ± 0.58) ng/ml,(6.24 ± 1.87) ng/ml,(6.11 ± 0.08) ng/ml;the levels of serum GFAP on day 1,3 and 7 in the severe abnormal group of craniocerebral MRI were as follows:(6.17 ± 1.34) ng/ml,(7.22 ± 0.91) ng/ml,(7.73 ± 1.01)ng/ml.Among the three groups of abnormal group of craniocerebral MRI,there were no significant differences in serum GFAP levels on day 1 and 3 (P ＞ 0.05),and there were significant differences on day 7 (P ＜ 0.05).Conclusions It is speculated that the increase of serum GFAP level in HIE newborns is related to the severity and prognosis of the disease,and is positively related to the results of craniocerebral MRI examination.Detecting the changes of serum GFAP in HIE newborns is helpful to determine the severity of the disease and evaluate the prognosis of the children.Combining GFAP with craniocerebral MRI may improve the accuracy of the judgment.
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BackgroundThe recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. A subset of COVID-19 patients progresses to severe disease, with high mortality and limited treatment options. Detailed knowledge of the expression regulation of genes required for viral entry into respiratory epithelial cells is urgently needed. MethodsHere we assess the expression patterns of genes required for SARS-CoV-2 entry into cells, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). FindingsGenes encoding viral receptors and activating protease are increased in the nose compared to the bronchi in matched samples and associated with the proportion of secretory epithelial cells in cellular deconvolution analyses. Current or ex-smoking was found to increase expression of these genes only in lower airways, which was associated with a significant increase in the predicted proportion of goblet cells. Both acute and second hand smoke exposure were found to increase ACE2 expression while inhaled corticosteroids decrease ACE2 expression in the lower airways. A strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified. InterpretationGenes associated with SARS-CoV-2 viral entry into cells are high in upper airways, but strongly increased in lower airways by smoke exposure. In contrast, ICS decreases ACE2 expression, indicating that inhaled corticosteroids are unlikely to increase the risk for more severe COVID-19 disease. FundingThis work was supported by a Seed Network grant from the Chan Zuckerberg Initiative to M.C.N. and by the European Unions H2020 Research and Innovation Program under grant agreement no. 874656 (discovAIR) to M.C.N. U BIOPRED was supported by an Innovative Medicines Initiative Joint Undertaking (No. 115010), resources from the European Unions Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution (www.imi.europa.eu). Longfonds Junior Fellowship. We acknowledge the contribution of the whole U-BIOPRED team as listed in the Appendix S1. SDB, FM and RFS would like to thank the Helmholtz Association, Germany, for support." NIH K08HL146943; Parker B. Francis Fellowship; ATS Foundation/Boehringer Ingelheim Pharmaceuticals Inc. Research Fellowship in IPF. RCR is part funded by Cancer Research UK Cambridge Centre and the Cambridge NIHR Biomedical Research Centre. BAP was funded by programme support from Cancer Research UK. The CRUKPAP Study was supported by the CRUK Cambridge Cancer Centre, by the NIHR Cambridge Biomedical Research Centre and by the Cambridge Bioresource. PIAMA was supported by The Netherlands Organization for Health Research and Development; The Netherlands Organization for Scientific Research; The Netherlands Lung Foundation (with methylation studies supported by AF 4.1.14.001); The Netherlands Ministry of Spatial Planning, Housing, and the Environment; and The Netherlands Ministry of Health, Welfare, and Sport. Dr. Qi is supported by a grant from the China Scholarship Council.