Generation and phenotypic analysis of Fbxo22 knockout mice / 上海交通大学学报（医学版）

Objective • To establish the Fbxo22 knockout mouse model and study the biological function of FBXO22. Methods • The Fbxo22 knockout mice were generated by CRISPR-Cas9 technology. The number, appearance, weight of different embryos and mice were measured. Meanwhile, the food intake and survival of Fbxo22-/- mice were analyzed. Results • Although the Fbxo22-/- embryos were present at approximately Mendelian ratios on embryonic day 17.5/18.5, most of them died within 48 hours of birth. Furthermore, those surviving Fbxo22-/- mice showed reduced body size and food intake and decreased life span. Conclusion • FBXO22 is an important, albeit not essential, protein for early postnatal survival and normal development.

Generation and phenotypic analysis of Fbxo22 knockout mice / 上海交通大学学报（医学版）

Objective · To establish the Fbxo22 knockout mouse model and study the biological function of FBXO22. Methods · The Fbxo22 knockout mice were generated by CRISPR-Cas9 technology. The number, appearance, weight of different embryos and mice were measured. Meanwhile, the food intake and survival of Fbxo22-/- mice were analyzed. Results · Although the Fbxo22-/- embryos were present at approximately Mendelian ratios on embryonic day 17.5/18.5, most of them died within 48 hours of birth. Furthermore, those surviving Fbxo22-/- mice showed reduced body size and food intake and decreased life span. Conclusion · FBXO22 is an important, albeit not essential, protein for early postnatal survival and normal development.

Application value of regional cerebral oxygenation monitoring in early neonates / 中国小儿急救医学

Regional cerebral oxygenation(rSO2) is widely used in the monitoring of cerebral blood flow,which is not affected by temperature and pulsatile blood flow.rSO2monitoring gives us a new way to monitor the oxygenation status of brain regions.But,currently,rSO2research in the neonates is rare.This pa-per summarized the different pathological conditions influence on early neonatal rSO2,clarified the important clinical significance of monitoring of neonatal rSO2and the future application was prospected.

Effects of overfeeding in breastfeeding period on blood pressure and vascular endothelial dilation function of rats / 中华临床营养杂志

Objective To study the effects of postnatal overfeeding and high-fat diet on blood pressure of rats,and to explore the pathophysiological mechanism underlying hypertension induced by continuous early postnatal overfeeding.Methods Male Sprague-Dawley rats were randomly divided into normal feeding group (10/litter) and overfeeding group (3/litter) on postnatal day 3 with a random number table.After weaning at postnatal week 3,the rats were randomly given standard chow or high-fat (HF) diet until week 16.Hence four groups were analyzed,namely normal feeding group,breastfed overfeeding group,post-weaning overfeeding group,and continuous overfeeding group.Body weight was continuously monitored in each week.Visceral fat pad (retroperitoneal and perigenital),systolic pressure,and heart rate were observed at week 3 and week 16.Thoracic aorta was sampled for measurement of vascular endothelial dilation function.Histological morphology was observed with HE staining,nitric oxide content of thoracic aorta was detected with nitrate reductase method.The mRNA expression of endothelial nitric oxide synthase (eNOS) in thoracic aorta was determined by real-time polymerase chain reaction.The protein expressions of eNOS and phosphorylated eNOS were determined by Western blot.Results At week 3,breastfed overfeeding rats displayed significantly larger body weight [(77.80 ± 0.57) g vs.(62.80 ±0.85) g,t =14.576,P ＜ 0.01] and visceral fat [retroperitoneal:(8.19 ± 0.49) mg/g vs.(4.92 ± 0.31) mg/g,t =5.629,P＜0.01;perigenital:(3.50 ±0.29) mg/g vs.(2.08 ±0.13) mg/g,t =4.552,P ＜0.01] compared with normal feedindg rats,and the protein expression of phosphorylated eNOS in aortic tissues was significantly reduced to week 16 (F =15.215,P ＜0.01);high-fat diet feeding after weaning further increased the body weight and fat mass in breastfed overfeeding rats.At week 16,continuous overfeeding rats showed hypertension [(149 ± 1.94) mmHg (1 mmHg =0.133 kPa),F =22.834,P ＜0.01],impaired vascular endothelial dilation function (F =7.648,P ＜ 0.05),and reduced protein expression of phosphorylated eNOS (F =15.215,P ＜ 0.01),while the post-weaning overfeeding group only had elevated blood pressure.Conclusions Overfeeding in breastfeeding period and high-fat diet after weaning leads to hypertension.The continuous decrease in phosphorylated eNOS in vascular tissues may be an important molecular process participating in the occurrence of vascular endothelial dysfunction in adults induced by postnatal overfeeding.

Neonatal hyper- and hypothyroidism alter the myoglobin gene expression program in adulthood

Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.

Reproductive response in offspring male rats exposed to prenatal stress and to early postnatal stimulation / Respuestas reproductivas en ratas estresadas prenatalmente, expuestas a estimulación postnatal

Stress in pregnant rats alters the pattern of secretion of corticosterone (COR) and modifies transplacentally hypothalamic-pituitary-adrenal axis (HPA) fetus. Prenatal stress during the critical hypothalamic differentiation is related to decreased fertility of male offspring by an increase in the basal level of COR. This modification could induce long-term changes in the process of apoptosis in the testis. However, early postnatal handling increases maternal behavior and could reverse the effects caused by increased secretion of COR. The aim of this research was to investigate the effects of early postnatal stimulation of male rats prenatal stressed by chronic immobilization during the last two weeks of pregnancy, on the hypothalamic-pituitary-gonadal axis and their relationship with the activity of the HPA. Male Wistar rats 3 month olds, were separated in four groups: (a) prenatally stressed animals by immobilization (IMO), without postnatal stimulation; (b) prenatally stressed animals with postnatal stimulation; (c) control animals without prenatal stress, without postnatal stimulation and (d) control animals without prenatal stress, with postnatal stimulation. In different animals groups plasmatic levels of COR, Testosterone (T) and Luteinizing Hormone (LH) were analyzed. Gonadosomatic index and testicular apoptosis was determined. In conclusion that prenatal stress by IMO increased levels of COR and inhibits the HHG axis obtaining low values of plasmatic LH and T, testicular weight, and induction of apoptosis in testes. On other hand, early postnatal stimulation results in an increase in maternal care to the offspring reversing the effects of prenatal stress on the HPG axis. This effect could be mediated by a mechanism independent of the HPA axis.

El estrés en ratas preñadas altera el patrón de secreción de corticosterona (COR) materna la cual, por vía transplacentaria, produce una alteración del eje Hipotálamo-Hipófiso-Adrenal (HHA) fetal. El estrés prenatal producido durante la etapa crítica de diferenciación hipotalámica, está relacionado con la disminución de la fertilidad en las crías macho, por un aumento en el nivel de COR basal. Esta modificación podría inducir cambios a largo plazo en el proceso de apoptosis testicular. Sin embargo, la estimulación postnatal temprana mejora el comportamiento materno, revirtiendo las alteraciones producidas por el aumento de COR en las crías adultas. El objetivo fue investigar el efecto de la estimulación postnatal temprana sobre el eje Hipotálamo-Hipófiso-Gonadal (HHG) en ratas macho estresadas prenatalmente (EP), por inmovilización crónica durante las dos últimas semanas de la preñez. Se utilizaron crías de 3 meses de edad, que fueron divididas en 4 grupos: (a) individuos EP y sin estimulación postnatal; (b) individuos EP con estimulación postnatal; (c) individuos controles no estresados prenatalmente (CP) y sin estimulación postnatal; y (d) individuos CP con estimulación postnatal. En todos los grupos se midió COR, Testosterona (T) y Hormona Luteinizante (LH). Se determinaron la apoptosis y la Caspasa 3 testicular y el índice gonadosomático. Se concluye que el estrés prenatal por inmovilización aumenta los niveles de COR del eje HHA e inhibe el eje HHG obteniendo valores bajos de LH y T plasmáticas. Se observa disminución del tamaño testicular y aumento de la apoptosis de las células testiculares. Por otro lado, la estimulación postnatal temprana se traduce en un aumento del cuidado materno hacia la cría, lo que revierte los efectos producidos por el estrés prenatal sobre el eje HHG. Este efecto podría estar mediado por algún mecanismo independiente del eje HHA.

Is there an association between perinatal complications and ttention-deficit/hyperactivity disorder-inattentive type in children and adolescents? / Existe alguma associação entre complicações perinatais e transtorno de déficit de atenção/hiperatividade - subtipo desatento em crianças e adolescentes?

OBJECTIVE: The objective of the present study is to investigate the association between attention deficit/hyperactivity disorder (ADHD), predominantly inattentive type (ADHD-I) and prenatal, delivery and early postnatal complications (PDPC). METHOD: In a case-control design, we assessed a sample of 124 children and adolescents with ADHD-I and 124 non-ADHD controls (6-17 years old) from both a non-referred (n = 200) and a clinical sample (n = 48). Cases and controls, matched by gender and age, were systematically evaluated through structured diagnostic interviews. Prenatal, delivery and early postnatal complications (PDPC), as well as potential confounders were evaluated by direct interview with biological mothers. RESULTS: Conditional logistic regression analysis showed that children and adolescents whose mothers presented more PDPC had a significantly higher risk for ADHD-I (p = 0.005; OR = 1.25; CI 95%: 1.1-1.5). CONCLUSIONS: In a case-control study, we expanded to ADHD-I previous findings suggesting the association between perinatal factors and broadly defined ADHD. Due to the preventable nature of some of these PDPC, our results have clear impact in public mental health policies.

OBJETIVO: O objetivo desse estudo é investigar a associação entre complicações perinatais (complicações ocorridas nos períodos pré, peri e pós-natal imediato -CPPs) e transtorno de déficit de atenção/hiperatividade (TDAH) do subtipo desatento (TDAH-D). MÉTODO: Em um estudo de casos e controles, foram avaliadas 124 crianças e adolescentes (6-17 anos) com TDAH-D e 124 controles sem a doença, provenientes tanto de uma amostra populacional (n = 200), quanto de uma amostra clínica (n = 48). Casos e controles, pareados por gênero e idade, foram sistematicamente avaliados através de entrevistas diagnósticas estruturadas. Informações sobre as complicações ocorridas durante os períodos pré, peri e pós-natal imediato (CPPs), assim como sobre potencias confundidores, foram obtidas através de entrevistas realizadas diretamente com as mães biológicas. RESULTADOS:A análise de regressão logística condicional mostrou que para as crianças e adolescentes cujas mães apresentaram maior número de CPPs, o risco de TDAH-D foi significativamente mais elevado (p = 0.005; OR = 1.25; IC 95%: 1.1-1.5). CONCLUSÕES: Em um estudo de caso-controle, foi possível expandir, para o TDAH predominantemente desatento, os achados prévios que sugeriam a associação entre complicações perinatais e TDAH sem um subtipo específico. Em virtude da possibilidade de prevenção de algumas dessas complicações, nossos resultados podem exercer impacto sobre políticas públicas de saúde.

Detailed Differentiation of Calbindin D-28k-Immunoreactive Cells in the Dentate Gyrus in C57BL/6 Mice at Early Postnatal Stages / 한국실험동물학회지

The hippocampus makes new memories and is involved in mental cognition, and the hippocampal dentate gyrus (DG) is critical because neurogenesis, which occurs throughout life, occurs in the DG. We observed the differentiation of neuroblasts into mature neurons (granule cells) in the DG of C57BL/6 mice at various early postnatal (P) ages: P1, P7, P14, and P21 using doublecortin (DCX) immunohistochemistry (IHC) for neuroblasts and calbindin D-28k (CB) IHC for granule cells. DCX-positive cells decreased in the DG with age; however, CB+ cells increased over time. At P1, DCX and CB double-labeled (DCX+CB+) cells were scattered throughout the DG. At P7, DCX+CB+ cells (about 92% of CB+ cells) were seen only in the granule cell layer (GCL) of the dorsal blade. At P14, DCX+CB+ cells (about 66% of CB+ cells) were found in the lower half of the GCL of both blades. In contrast, at P21, about 18% of CB+ cells were DCX+CB+ cells, and they were mainly located only in the subgranular zone of the DG. These results suggest that the developmental pattern of DCX+CB+ cells changes with time in the early postnatal stages.

Association of Early Postnatal Neutropenia and Development of Bronchopulmonary Dysplasia in Preterm Infants

PURPOSE: To see if a similar relationship exists between the decreased number of circulating neutrophils and the development of bronchopulmonary dysplasia (BPD) in preterm infants, we tried to test the hypothesis that claims that preterm infants, who develop BPD, have decreased number of circulating neutrophils than those who do not develop BPD. METHODS: A retrospective cohort study was conducted in 167 preterm infants from August 1995 to July 1997, who were admitted in the neonatal intensive care unit (NICU) of Seoul National University Children's Hospital. RESULTS: BPD was diagnosed in 16% (27/167) of preterm infants. We compared the clinical characteristics of the study population according to the presence or absence of BPD. Compared to non-BPD group, the BPD group had a lower gestational age (29.4 +/- 2.7weeks versus 32.7 +/- 1.7 weeks), lower birth weight (1,240 +/- 486g versus 1,780 +/- 420g), lower incidence of prenatal steroid use (2/27 versus 41/140), decreased number of circulating neutrophils (3,622 +/- 4,866/microliter versus 7,586 +/- 4,545/microliter) at 1 day of life. After adjusting for the variables of the above risk factors, neutropenia (<2,500/microliter) in the peripheral blood increased the odds ratio of developing BPD (OR : 46.3, 95% CI : 17.3-117.2). CONCLUSION: Early postnatal neutropenia might be an important risk factor for the development of BPD and lung injury responsible for the development of BPD might begin at the early postnatal period.

Association of Early Postnatal Neutropenia and Development of Bronchopulmonary Dysplasia in Preterm Infants

PURPOSE: To see if a similar relationship exists between the decreased number of circulating neutrophils and the development of bronchopulmonary dysplasia (BPD) in preterm infants, we tried to test the hypothesis that claims that preterm infants, who develop BPD, have decreased number of circulating neutrophils than those who do not develop BPD. METHODS: A retrospective cohort study was conducted in 167 preterm infants from August 1995 to July 1997, who were admitted in the neonatal intensive care unit (NICU) of Seoul National University Children's Hospital. RESULTS: BPD was diagnosed in 16% (27/167) of preterm infants. We compared the clinical characteristics of the study population according to the presence or absence of BPD. Compared to non-BPD group, the BPD group had a lower gestational age (29.4 +/- 2.7weeks versus 32.7 +/- 1.7 weeks), lower birth weight (1,240 +/- 486g versus 1,780 +/- 420g), lower incidence of prenatal steroid use (2/27 versus 41/140), decreased number of circulating neutrophils (3,622 +/- 4,866/microliter versus 7,586 +/- 4,545/microliter) at 1 day of life. After adjusting for the variables of the above risk factors, neutropenia (<2,500/microliter) in the peripheral blood increased the odds ratio of developing BPD (OR : 46.3, 95% CI : 17.3-117.2). CONCLUSION: Early postnatal neutropenia might be an important risk factor for the development of BPD and lung injury responsible for the development of BPD might begin at the early postnatal period.