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The UK screening and treatment of retinopathy of prematurity (ROP) updated 2022 guidelines were developed by a multidisciplinary guideline development group from the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists, following the standards of the National Institute for Health and Care Excellence. They were published on the websites of the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists in March 2022, and formally published in Early Human Development in March 2023. The guidelines provide evidence-based recommendations for the screening and treatment of ROP. The most significant change in the 2022 updated version compared to the previous guidelines is the lowering of the gestational age screening criterion to below 31 weeks. The treatment section covers treatment indications, timing, methods, and follow-up visits of ROP. This article interprets the guidelines and compares them with ROP guidelines/consensus in China, providing a reference for domestic peers.
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Guías de Práctica Clínica como Asunto , Retinopatía de la Prematuridad , Humanos , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/terapia , Recién Nacido , Reino Unido , Tamizaje Neonatal , Edad GestacionalRESUMEN
The "Guidelines for parenteral nutrition in preterm infants: the American Society for parenteral and enteral nutrition" were developed by the American Society for Parenteral and Enteral Nutrition and published in the Journal of Parenteral and Enteral Nutrition in September 2023. The guidelines provide recommendations on 12 key clinical questions regarding parenteral nutrition (PN) for preterm infants. In comparison to similar guidelines, this set offers more detailed perspectives on PN for preterm infants. It presents evidence-based recommendations for the commencement time, nutrient dosage, and composition of PN, considering primary outcomes such as growth and development, as well as secondary outcomes like sepsis, retinopathy of prematurity, parenteral nutrition-related liver disease, and jaundice. This article aims to interpret the guidelines to provide a reference for colleagues in the field.
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Nutrición Enteral , Recien Nacido Prematuro , Nutrición Parenteral , Guías de Práctica Clínica como Asunto , Humanos , Nutrición Parenteral/normas , Nutrición Parenteral/métodos , Recién Nacido , Nutrición Enteral/normas , Nutrición Enteral/métodos , Sociedades MédicasRESUMEN
The available data on the localization of transforming growth factor beta1 (TGF-ß1), glial cell line-derived neurotrophic factor (GDNF), and platelet-derived growth factor-BB (PDGF-BB) in the adult primate and human central nervous system (CNS) are limited and lack comprehensive and systematic information. This study aimed to investigate the cellular localization and distribution of TGF-ß1, GDNF, and PDGF-BB in the CNS of adult rhesus macaque (Macaca mulatta). Seven adult rhesus macaques were included in the study. The protein levels of TGF-ß1, PDGF-BB, and GDNF in the cerebral cortex, cerebellum, hippocampus, and spinal cord were analyzed by western blotting. The expression and location of TGF-ß1, PDGF-BB, and GDNF in the brain and spinal cord was examined by immunohistochemistry and immunofluorescence staining, respectively. The mRNA expression of TGF-ß1, PDGF-BB, and GDNF was detected by in situ hybridization. The molecular weight of TGF-ß1, PDGF-BB, and GDNF in the homogenate of spinal cord was 25 KDa, 30 KDa, and 34 KDa, respectively. Immunolabeling revealed GDNF was ubiquitously distributed in the cerebral cortex, hippocampal formation, basal nuclei, thalamus, hypothalamus, brainstem, cerebellum, and spinal cord. TGF-ß1 was least distributed and found only in the medulla oblongata and spinal cord, and PDGF-BB expression was also limited and present only in the brainstem and spinal cord. Besides, TGF-ß1, PDGF-BB, and GDNF were localized in the astrocytes and microglia of spinal cord and hippocampus, and their expression was mainly found in the cytoplasm and primary dendrites. The mRNA of TGF-ß1, PDGF-BB, and GDNF was localized to neuronal subpopulations in the spinal cord and cerebellum. These findings suggest that TGF-ß1, GDNF and PDGF-BB may be associated with neuronal survival, neural regeneration and functional recovery in the CNS of adult rhesus macaques, providing the potential insights into the development or refinement of therapies based on these factors.
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Factor Neurotrófico Derivado de la Línea Celular Glial , Factor de Crecimiento Transformador beta1 , Animales , Becaplermina , Macaca mulatta/metabolismo , ARN Mensajero , Médula Espinal/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
International guidelines regarding the role of intravenous immunoglobulin (IVIG) in the management of Rh- and ABO-mediated haemolytic disease of the newborn was drafted by an international panel of experts in the fields of hematology, neonatology, and blood transfusion and was published in British Journal of Haematology on March 16, 2022. The guidelines summarize the evidence-based practice of IVIG in Rh- and ABO-mediated haemolytic disease of the newborn and propose related recommendations. The guidelines recommend that IVIG should not be applied as a routine treatment regimen for Rh- and ABO-mediated haemolytic disease of the newborn in order to reduce exchange transfusion (ET), and the best time to apply IVIG remains unclear in the situations where hyperbilirubinaemia is severe (approaching or exceeding the ET threshold) or ET cannot be implemented. These guidelines are formulated with rigorous methods, but with the lower quality of evidence.
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Eritroblastosis Fetal , Enfermedades Hematológicas , Recién Nacido , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Eritroblastosis Fetal/tratamiento farmacológico , Recambio Total de Sangre , HiperbilirrubinemiaRESUMEN
OBJECTIVE: To study the role and mechanism of histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2) in mouse neuronal development. METHODS: The mice with Synapsin1-Cre recombinase were bred with HDAC1&2flox/flox mice to obtain the mice with neuron-specific HDAC1&2 conditional knockout (knockout group), and their littermates without HDAC1&2 knockout were used as the control group. The general status of the mice was observed and survival curves were plotted. Brain tissue samples were collected from the knockout group and the control group. Western blot and immunohistochemistry were used to measure the protein expression of related neuronal and axonal markers, neuronal nuclear antigen (NeuN), non-phosphorylated neurofilament heavy chain (np-NF200), and phosphorylated neurofilament heavy chain (p-NF200), as well as the downstream effector of the mTOR signaling pathway, phosphorylated S6 ribosomal protein (p-S6). RESULTS: The mice with HDAC1&2 conditional knockout usually died within one month after birth and were significantly smaller than those in the control group, with motor function abnormalities such as tremor and clasping of hindlimbs. Compared with the control group, the knockout group had significant reductions in the protein expression levels of NeuN, np-NF200, p-NF200, and p-S6 (P < 0.05; n=3). CONCLUSIONS: Deletion of HDAC1 and HDAC2 in mouse neurons results in reduced neuronal maturation and axonal dysplasia, which may be associated with the mTOR signaling pathway.
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Histona Desacetilasa 2 , Histona Desacetilasas , Animales , Western Blotting , Histona Desacetilasa 1/genética , Histona Desacetilasas/genética , Inmunohistoquímica , Ratones , Neuronas/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: To systematically summarize the clinical features of coronavirus disease 2019 (COVID-19) in children. METHODS: PubMed, Embase, Web of Science, The Cochrane Library, CNKI, Weipu Database, and Wanfang Database were searched for clinical studies on COVID-19 in children published up to May 21, 2020. Two reviewers independently screened the articles, extracted data, and assessed the risk of bias of the studies included. A descriptive analysis was then performed for the studies. Related indices between children with COVID-19 and severe acute respiratory syndromes (SARS) or Middle East respiratory syndrome (MERS) were compared. RESULTS: A total of 75 studies were included, with a total of 806 children with COVID-19. The research results showed that the age of the children ranged from 36 hours after birth to 18 years, with a male-female ratio of 1.21 : 1. Similar to SARS and MERS, COVID-19 often occurred with familial aggregation, and such cases accounted for 74.6% (601/806). The children with COVID-19, SARS, and MERS had similar clinical symptoms, mainly fever and cough. Some children had gastrointestinal symptoms. The children with asymptomatic infection accounted for 17.9% (144/806) of COVID-19 cases, 2.5% (2/81) of SARS cases, and 57.1% (12/21) of MERS cases. The children with COVID-19 and MERS mainly had bilateral lesions on chest imaging examination, with a positive rate of lesions of 63.4% (421/664) and 26.3% (5/19) respectively, which were lower than the corresponding positive rates of viral nucleic acid detection, which were 99.8% and 100% respectively. The chest radiological examination of the children with SARS mainly showed unilateral lesion, with a positive rate of imaging of 88.9% (72/81), which was higher than the corresponding positive rate of viral nucleic acid detection (29.2%). Viral nucleic acid was detected in the feces of children with COVID-19 or SARS, with positive rates of 60.2% (56/93) and 71.4% (5/7) respectively. The children with COVID-19 had a rate of severe disease of 4.6% (31/686) and a mortality rate of 0.1% (1/806), the children with SARS had a rate of severe disease of 1.5% (1/68) and a mortality rate of 0%, and those with MERS had a rate of severe disease of 14.3% (3/21) and a mortality rate of 9.5% (2/21). CONCLUSIONS: Children with COVID-19 have similar symptoms to those with SARS or MERS, mainly fever and cough. Asymptomatic infection is observed in all three diseases. Children with COVID-19 or SARS have milder disease conditions than those with MERS. COVID-19 in children often occurs with familial aggregation. Epidemiological contact history, imaging examination findings, and viral nucleic acid testing results are important bases for the diagnosis of COVID-19.
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Infecciones por Coronavirus/fisiopatología , Neumonía Viral/fisiopatología , Síndrome Respiratorio Agudo Grave/fisiopatología , Síndrome Respiratorio Agudo Grave/virología , Betacoronavirus , COVID-19 , Niño , Tos/virología , Femenino , Fiebre/virología , Humanos , Masculino , Coronavirus del Síndrome Respiratorio de Oriente Medio , Pandemias , SARS-CoV-2RESUMEN
OBJECTIVE: To study the effect and mechanism of action of irisin on hypoxic-ischemic brain damage in neonatal rats. METHODS: A total of 248 7-day-old Sprague-Dawley rats were randomly divided into a sham-operation group, a model group, and low- and high-dose irisin intervention groups (n=62 each). The rats in the model and irisin intervention groups were given hypoxic treatment after right common carotid artery ligation to establish a model of hypoxic-ischemic brain damage. Those in the sham-operation group were given the separation of the right common carotid artery without ligation or hypoxic treatment. The rats in the high- and low-dose irisin intervention groups were given intracerebroventricular injection of recombinant irisin polypeptide at a dose of 0.30 µg and 0.15 µg respectively. Those in the model and sham-operation groups were given the injection of an equal volume of PBS. The water maze test was used to compare neurological behaviors between groups. TTC staining, hematoxylin-eosin staining and TUNEL staining were used to observe histopathological changes of the brain. Western blot was used to measure the expression of the apoptosis-related molecules cleaved-caspase-3 (CC3), BCL-2 and BAX. RESULTS: Compared with the sham-operation group, the model group had a significant increase in latency time and a significant reduction in the number of platform crossings (P<0.05). Compared with the model group, the high-dose irisin intervention group had a significant reduction in latency time and a significant increase in the number of platform crossings (P<0.05). Compared with the sham-operation group, the model group had massive infarction in the right hemisphere, with significant increases in karyopyknosis and karyorrhexis. Compared with the model group, the high-dose irisin intervention group had a smaller infarct area of the right hemisphere, with reductions in karyopyknosis and karyorrhexis. The model group had a significantly higher apoptosis rate of cells in the right cerebral cortex and the hippocampus than the sham-operation group. The high-dose irisin intervention group had a significantly lower apoptosis rate than the model group (P<0.05). At 24 and 48 hours after modeling, the sham-operation group had a significantly lower level of CC3 than the model group (P<0.05). Compared with the model group, the high-dose irisin intervention group had a significantly lower level of CC3 and a significantly higher BCL-2/BAX ratio (P<0.05). The low-dose irisin intervention group had similar laboratory markers and histopathological changes of the brain to the model group. CONCLUSIONS: Irisin can alleviate hypoxic-ischemic brain damage in neonatal rats in a dose-dependent manner, possibly by reducing cell apoptosis in the cerebral cortex and the hippocampus.
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Hipoxia-Isquemia Encefálica , Animales , Animales Recién Nacidos , Apoptosis , Encéfalo , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To compare the effect and safety of prednisolone and adrenocorticotropic hormone (ACTH) in the treatment of infantile spasms (IS). METHODS: Cochrane Library, Embase, PubMed, China Biology Medicine Disc, CNKI, and Wanfang Data were searched for clinical studies on the comparison between prednisolone and ACTH in the treatment of IS. Literature screening, data extraction, and quality assessment were performed. Review Manager 5.3 was used for Meta analysis. RESULTS: Five clinical studies were included according to the inclusion criteria and exclusion criteria. Meta analysis showed that there was no significant difference in the spasm remission rate, spasm remission time, complicating infection rate, and irritability rate between the prednisolone and ACTH treatment groups (P>0.05), but the disappearance rate of hypsarrhythmia in the electroencephalogram was higher in the ACTH treatment group than in the prednisolone treatment group (P<0.05). CONCLUSIONS: The available evidence shows no difference in the clinical efficacy of prednisolone versus ACTH in the treatment of IS. However, ACTH is superior to prednisolone in stabilizing EEG. The two therapies have no difference in the incidence of adverse reactions such as infection and irritability.
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Espasmos Infantiles , Hormona Adrenocorticotrópica , Anticonvulsivantes , China , Humanos , Lactante , Prednisolona , Espasmo , Resultado del TratamientoRESUMEN
OBJECTIVE: To perform a review and data analysis of the pediatric projects funded by National Natural Science Foundation of China from 2009 to 2018, and to investigate the changes in key support areas, research interest, and research hotspots in pediatrics. METHODS: The database of National Natural Science Foundation of China was searched to screen out pediatric research projects in 2009-2018, and the changes in funding intensity and research direction were analyzed. RESULTS: From 2009 to 2018, a total of 1 017 pediatric projects were funded by National Natural Science Foundation of China, with 485 (47.69%) General Projects, 426 (41.89%) Youth Fund Projects, 73 (7.18%) Regional Research Programs, 16 (1.57%) Key Programs, 6 (0.59%) Outstanding Youth Fund Projects, 7 (0.69%) Overseas Programs, and 4 (0.39%) other programs. There was a seven-fold increase in the total amount of subsidies, which increased from 8.42 million yuan in 2009 to 66.25 million yuan in 2018. The projects with the Primary Discipline Code of reproductive system/perinatology/neonatology, nervous system and mental illness, or circulatory system received the highest amount of fund. CONCLUSIONS: The support of pediatric projects by National Natural Science Foundation of China continues to increase in the past ten years, and the main types of projects are General Projects and Youth Fund Projects. Neonatology, nervous system/mental illness, and circulatory diseases are the main directions of funded projects.
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Disciplinas de las Ciencias Naturales , Adolescente , Niño , China , Administración Financiera , Fundaciones , Humanos , NeonatologíaRESUMEN
Preterm infants are a special group, and related severe neurological, respiratory, and digestive disorders have high disability/fatality rates. Allogeneic cell transplantation may be an effective method for the prevention and treatment of these diseases. At present, animal studies have been conducted for allogeneic cell transplantation in the treatment of hypoxic-ischemic encephalopathy, bronchopulmonary dysplasia, and necrotizing enterocolitis. The main difficulty of this technique is graft-versus-host reaction (GVHR), and successful induction of immune tolerance needs to be achieved in order to solve this problem. This article reviews the research advances in immune tolerance of allogeneic cell transplantation in preterm infants.
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Trasplante de Células , Tolerancia Inmunológica , Apoptosis , Trasplante de Células/efectos adversos , Citocinas/fisiología , Reacción Injerto-Huésped , Humanos , Recién Nacido , Recien Nacido Prematuro/inmunología , Trasplante HomólogoRESUMEN
White matter injury in preterm infants has a complex etiology and can lead to long-term neurocognitive and behavioral deficits, but there are still no specific treatment methods for this disease at present. More and more studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of white matter injury in preterm infants and might be a common subcellular mechanism of white matter developmental disorder, which involves oxidative stress, reduced ATP synthesis, and disequilibrium of calcium homeostasis. This article reviews the role of mitochondria in brain development and the mechanism of mitochondrial dysfunction, with a hope to perform early intervention of white matter injury in preterm infants by protecting mitochondrial function, so as to provide a reference for improving the neurodevelopmental outcome of preterm infants who survive.
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Lesiones Encefálicas , Sustancia Blanca , Encéfalo , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Imagen por Resonancia Magnética , MitocondriasRESUMEN
White matter damage, characterized by demyelination due to the damage of oligodendrocyte precursor cells (OPCs), is the most common type of brain damage in preterm infants. Survivors are often subject to long-term neurodevelopmental sequelae because of the lack of effective treatment. In recent years, it has been found that cell transplantation has the potential for the treatment of white matter damage. OPCs are frequently used cells in cell transplantation therapy. With abilities of migration and myelinization, OPCs are the best seed cells for the treatment of white matter damage. Several studies have found that OPCs may not only replace impaired cells to reconstruct the structure and function of white matter, but also inhibit neuronal apoptosis, promote the proliferation of endogenous neural stem cells, and enhance the repairment of the blood-brain barrier. However, the clinical application of OPC transplantation therapy faces many challenges, such as the effectiveness, risk of tumorigenesis and immune rejection. With reference to these studies, this article reviewed the development of myelination, the obtainment of OPCs, the therapeutic mechanism as well as application research, and analyzed the current challenges of OPC transplantation, in order to provide a new direction for clinical treatment of white matter damage in preterm infants.
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Enfermedades Desmielinizantes/terapia , Células Precursoras de Oligodendrocitos/trasplante , Sustancia Blanca/patología , Separación Celular , Humanos , Recién Nacido , Recien Nacido PrematuroRESUMEN
OBJECTIVE: To investigate the current status of the application of 1H-magnetic resonance spectroscopy (1H-MRS) in neonates with hypoxic-ischemic encephalopathy (HIE), and to describe the trend of research in the field. METHODS: PubMed, EMBASE, and Web of Science were searched for English articles published up to January 10, 2018, with the combination of key words and MeSH terms. The articles were screened according to inclusion and exclusion criteria. Excel 2016, Bicomb 2.0, and VOSviewer1.6.6 were used to analyze the key words, to perform a cluster analysis of hot words, and to plot the knowledge map. RESULTS: A total of 66 articles were included, and 27 high-frequency key words were extracted. The results showed that 1H-MRS was mainly used in four directions of the clinical practice and scientific research on HIE. In clinical practice, 1H-MRS attracted wide attention as a clinical examination for HIE and a tool for prognostic evaluation; in scientific research, 1H-MRS was used in animal experiments and studies associated with mild hypothermia therapy. CONCLUSIONS: As an auxiliary means of magnetic resonance imaging, 1H-MRS plays an important role in investigating the pathogenesis of neonatal HIE, improving existing therapies, and evaluating the prognosis of neonates with HIE.
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Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Enfermedades del Recién Nacido/diagnóstico por imagen , Imagen por Resonancia Magnética , Femenino , Humanos , Hipoxia-Isquemia Encefálica/diagnóstico , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
OBJECTIVE: To reveal the current research status on stem cell transplantation in the treatment of neonates with hypoxic-ischemic encephalopathy (HIE), and to summarize the recent hotspots of the research in this field. METHODS: Using the key words of "stem cells" and "HIE", a computerized search was performed for the articles in English published before June 1, 2018 in PubMed, EMBASE, and Web of Science. Microsoft Office Excel 2013 was used for the statistical analysis of key words. Bicomb 2.0 and VOSviewer 1.6.6 were used for the cluster analysis of hot words and plotting of knowledge maps, respectively. RESULTS: A total of 106 articles were included and 43 high-frequency key words were extracted. The words of "cell transplantation" and "hypoxia-ischemia" were in the core position of the co-word map. The cluster analysis showed that the studies of stem cell transplantation in the treatment of neonatal HIE mainly focused on umbilical cord blood cell transplantation (32.6%), mesenchymal stem cells and neural stem cells (29.5%), perinatal brain injury (28.1%), and other topics (9.8%). CONCLUSIONS: In the current studies of stem cell transplantation in the treatment of neonatal HIE, umbilical cord blood cell transplantation, mesenchymal stem cells, neural stem cells, and perinatal brain injury are popular research topics at different levels.
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Hipoxia-Isquemia Encefálica , Células Madre Mesenquimatosas , Humanos , Recién Nacido , Células-Madre Neurales , Trasplante de Células MadreRESUMEN
OBJECTIVE: To study the effect of astrocyte exosomes on hypoxic-ischemic neurons. METHODS: Rat astrocytes were cultured in vitro, and differential centrifugation was used to obtain the exosomes from the cell supernatant. Transmission electron microscopy, Nanosight, and Western blot were used for the identification of exosomes. BCA method was used to measure the concentration of exosomes. Rat neurons were cultured in vitro and then divided into control group, exosome group, oxygen glucose deprivation (OGD) group, and OGD+exosome group (n=3 each). The OGD and OGD+exosome groups were cultured in glucose-free medium under the hypoxic condition. The exosome and OGD+exosome groups were treated with exosomes at a final concentration of 22â μg/mL. The control and OGD groups were given an equal volume of phosphate-buffered saline. ELISA was used to measure the level of lactate dehydrogenase (LDH) in neurons. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the apoptotic index of neurons. RESULTS: The identification of exosomes showed that the exosomes extracted by differential centrifugation had the features of exosomes. Compared with the control and exosome groups, the OGD group had significant increases in LDH level and apoptotic index (P<0.05). Compared with the OGD group, the OGD+exosome group had significant reductions in LDH level and apoptotic index (P<0.05). CONCLUSIONS: The exosomes from astrocytes have a protective effect on neurons with hypoxic-ischemic injury.
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Astrocitos/fisiología , Exosomas/fisiología , Glucosa/deficiencia , Neuroprotección , Animales , Apoptosis , Hipoxia de la Célula , Células Cultivadas , Hidroliasas/análisis , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To study the effect of golden-hour body temperature bundle management strategy on admission temperature and clinical outcome in preterm infants with a gestational age of <34 weeks after birth. METHODS: The preterm infants who were born in the delivery room of the West China Second University Hospital of Sichuan University and admitted to the department of neonatology of this hospital within 1 hour after birth from December 2015 to June 2016 and from January to May, 2017 were enrolled. The 173 preterm infants who were admitted from January to May, 2017 were enrolled as the intervention group and were given golden-hour body temperature bundle management. The 164 preterm infants who were admitted from December 2015 to June 2016 were enrolled as the control group and were given conventional body temperature management. RESULTS: The intervention group had a significantly higher mean admission temperature than the control group (36.4±0.4°C vs 35.3±0.6°C; P<0.001). The incidence rate of hypothermia on admission in the intervention group was significantly lower than that in the control group (56.6% vs 97.6%; P<0.001). The intervention group had a significantly lower incidence rate of intracranial hemorrhage within one week after admission than the control group (15.0% vs 31.7%; P<0.05). CONCLUSIONS: Golden-hour body temperature bundle management for preterm infants within one hour after birth can reduce the incidence of hypothermia on admission and improve clinical outcome.
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Temperatura Corporal , Hipotermia/terapia , Enfermedades del Prematuro/terapia , China , Femenino , Edad Gestacional , Hospitalización , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/fisiopatología , Masculino , Factores de TiempoRESUMEN
OBJECTIVES: To determine the therapeutic effect and protective mechanism of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on newborn rats with hypoxia ischemic brain damage (HIBD). METHODS: Umbilical cord (3-4 cm) was collected from a healthy male infant for preparation of hUC-MSCs using explants technique. The hUC-MSCs were cultured and labeled with BrdU. The differentiation function of MSCs was identified. Healthy SPF grade neonatal SD rats were randomly divided into sham (n =30), HIBD (n =36) and hUC-MSCs treated HIBD (n =32) groups. BrdU-labeled hUC-MSCs were injected into the right ventricle of the rats in the hUC-MSCs treatment group 24 h after successful induction of HIBD. The growth and development of the rats were recorded. The neurological behavior of the rats were evaluated with Longa score method 3 weeks after hUC-MSCs transplantation. The survival, migration, differentiation and pro-differentiation of the transplanted hUC-MSCs were measured using immunological fluorescence method. RESULTS: Rats in the hUC-MSCs treatment group had significant higher weight gain and lower Longa scores (at the second and the third week post transplantation) than those in the HIBD group (P<0.05). BrdU positive cells were found in brain tissues 3 weeks after transplantation, and they were mainly distributed in the damaged hippocampus and cerebral cortex. Three weeks after transplantation, the total signal strength of glial fibrillary acidic protein (GFAP) or neuron-specific enclase (NSE) gradually increased. CONCLUSION: Transplanted hUC-MSCs can migrate brain damages through differentiating into neuron-like cells and promoting endogenous neurological differentiations.
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Hipoxia-Isquemia Encefálica/terapia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Cordón Umbilical/citología , Animales , Animales Recién Nacidos , Diferenciación Celular , Humanos , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
Mitophagy is a process during which the cell selectively removes the mitochondria via the mechanism of autophagy. It is crucial to the functional completeness of the whole mitochondrial network and determines cell survival and death. On the one hand, the damaged mitochondria releases pro-apoptotic factors which induce cell apoptosis; on the other hand, the damaged mitochondria eliminates itself via autophagy, which helps to maintain cell viability. Mitophagy is of vital importance for the development and function of the nervous system. Neural cells rely on autophagy to control protein quality and eliminate the damaged mitochondria, and under normal circumstances, mitophagy can protect the neural cells. Mutations in genes related to mitophagy may cause the development and progression of neurodegenerative diseases. An understanding of the role of mitophagy in nervous system diseases may provide new theoretical bases for clinical treatment. This article reviews the research advances in the relationship between mitophagy and different types of nervous system diseases.
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Autofagia/fisiología , Mitofagia , Enfermedades del Sistema Nervioso/etiología , Apoptosis , Humanos , Enfermedades Neurodegenerativas/etiologíaRESUMEN
Mesenchymal stem cell (MSC) transplantation is considered one of the most promising therapeutic strategies for the repair of brain injuries and plays an important role in various links of nerve repair. Recent studies have shown that MSC-derived exosomes may dominate the repair of brain injuries and help to promote angiogenesis, regulate immunity, inhibit apoptosis, and repair the nerves, and therefore, they have a great potential in the treatment of brain injuries in neonates. With reference to these studies, this article reviews the mechanism of action of exosomes in the repair of brain injuries and related prospects and challenges, in order to provide new directions for the treatment of brain injuries in neonates with stem cells.
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Lesiones Encefálicas/terapia , Exosomas/fisiología , Trasplante de Células Madre Mesenquimatosas , Apoptosis , Humanos , Inflamación/prevención & control , Neovascularización Fisiológica , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: To investigate mitophagy in an animal model of hypoxic-ischemic brain damage (HIBD) and its role in HIBD. METHODS: A total of 120 neonatal Sprague-Dawley rats aged 7 days were divided into three groups: sham-operation, HIBD, and autophagy inhibitor intervention (3MA group). The rats in the HIBD group were treated with right common carotid artery ligation and then put in a hypoxic chamber (8% oxygen and 92% nitrogen) for 2.5 hours. Those in the 3MA group were given ligation and hypoxic treatment at 30 minutes after intraperitoneal injection of 2 µL 3MA. Those in the sham-operation group were not given ligation or hypoxic treatment. Single cell suspension was obtained from all groups after model establishment. Immunofluorescence localization was performed for mitochondria labeled with MitoTracker, autophagosomes labeled with LysoTracker, and autophagy labeled with LC3 to observe mitophagy. After staining with the fluorescent probe JC-1, flow cytometry was used to measure mitochondrial membrane potential. TTC staining was used to measure infarct volume. Cytoplasmic proteins in cortical neurons were extracted, and Western blot was used to measure the expression of mitophagy-related proteins. RESULTS: Compared with the sham-operation group, the HIBD group had a significant reduction in mitochondrial membrane potential (P<0.05), a significant increase in mitophagy (P<0.05), a significant increase in the expression of the proteins associated with the division of the mitochondrial Drp1 and Fis1 (P<0.05), and a significant reduction in the expression of the mitochondrial outer membrane protein Tom20 and the mitochondrial inner membrane protein Tim23 (P<0.05). Compared with the HIBD group, the 3MA group had a significantly greater reduction in mitochondrial membrane potential (P<0.05), but showed significantly reduced mitophagy (P<0.05). In addition, the 3MA group had a significantly increased degree of cerebral infarction compared with the HIBD group (P<0.05). CONCLUSIONS: HIBD can increase the degree of mitophagy, and the inhibition of mitophagy can aggravate HIBD in neonatal rats.