Effectiveness of azithromycin mass drug administration on trachoma: a systematic review / 中华医学杂志(英文版)

BACKGROUNDS@#Azithromycin mass drug administration (MDA) is a key part of the strategy for controlling trachoma. This systematic review aimed to comprehensively summarize the present studies of azithromycin MDA on trachoma; provide an overview of the impact of azithromycin MDA on trachoma in different districts; and explore the possible methods to enhance the effectiveness of azithromycin MDA in hyperendemic districts.@*METHODS@#PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched up to February 2021 with no language restriction. Studies reporting the effect of azithromycin MDA on trachoma were included. Mathematical modeling studies, animal studies, case reports, and reviews were excluded. The trachomatous inflammation-follicular (TF) 30.0%), especially with baseline TF >50.0%, annual MDA was unable to achieve the TF 10.0% is not appropriate for all eligible districts.

Role and mechanism of histone deacetylases in mouse neuronal development / 中国当代儿科杂志

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 @*RESULTS@#The mice with @*CONCLUSIONS@#Deletion of

Effect of irisin on hypoxic-ischemic brain damage in neonatal rats / 中国当代儿科杂志

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.

Clinical features of coronavirus disease 2019 in children: a systemic review of severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019 / 中国当代儿科杂志

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.

Pediatric projects funded by National Natural Science Foundation of China from 2009 to 2018: retrospect and prospects / 中国当代儿科杂志

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.

Effect of prednisolone and adrenocorticotropic hormone in the treatment of infantile spasms: a Meta analysis / 中国当代儿科杂志

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.

Effect of golden-hour body temperature bundle management on admission temperature and clinical outcome in preterm infants after birth / 中国当代儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

A review on the relationship between mitochondrial dysfunction and white matter injury in preterm infants / 中国当代儿科杂志

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.

Neuroprotective effects of oligodendrocyte precursor cells on white matter damage in preterm infants / 中国当代儿科杂志

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.

Research advances in immune tolerance of allogeneic cell transplantation in preterm infants / 中国当代儿科杂志

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.

Protective effect of astrocyte exosomes on hypoxic-ischemic neurons / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of astrocyte exosomes on hypoxic-ischemic neurons.</p><p><b>METHODS</b>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 22 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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>The exosomes from astrocytes have a protective effect on neurons with hypoxic-ischemic injury.</p>

Current status of the application of H-magnetic resonance spectroscopy in neonates with hypoxic-ischemic encephalopathy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the current status of the application of H-magnetic resonance spectroscopy (H-MRS) in neonates with hypoxic-ischemic encephalopathy (HIE), and to describe the trend of research in the field.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>A total of 66 articles were included, and 27 high-frequency key words were extracted. The results showed that H-MRS was mainly used in four directions of the clinical practice and scientific research on HIE. In clinical practice, H-MRS attracted wide attention as a clinical examination for HIE and a tool for prognostic evaluation; in scientific research, H-MRS was used in animal experiments and studies associated with mild hypothermia therapy.</p><p><b>CONCLUSIONS</b>As an auxiliary means of magnetic resonance imaging, H-MRS plays an important role in investigating the pathogenesis of neonatal HIE, improving existing therapies, and evaluating the prognosis of neonates with HIE.</p>

A visualization analysis of current research on stem cell transplantation in the treatment of neonatal hypoxic-ischemic encephalopathy / 中国当代儿科杂志

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.

Research advances in mesenchymal stem cell-derived exosomes in treatment of brain injury / 中国当代儿科杂志

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.

Mitophagy and nervous system disease / 中国当代儿科杂志

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.

Effect of premature rupture of membranes on maternal infections and outcome of preterm infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of premature rupture of membranes (PROM) on maternal infections and outcome of preterm infants.</p><p><b>METHODS</b>A total of 441 preterm infants and 387 mothers were enrolled as subjects. According to the presence or absence of PROM, the mothers were divided into non-PROM group with 104 mothers, PROM duration <72 hours group with 90 mothers, and PROM duration ≥72 hours group with 193 mothers. The three groups were compared in terms of clinical features of mothers and infants and complications.</p><p><b>RESULTS</b>Compared with the control group and the PROM duration <72 hours group, the PROM duration ≥72 hours group had significantly higher maternal age, incidence rate of umbilical vasculitis, and rate of antibiotic use; the PROM duration ≥72 hours group had a significantly higher incidence rate of moderate-to-severe chorioamnionitis than the control group (P<0.05), while there was no significant difference between the PROM duration ≥72 hours group and the PROM duration <72 hours group (P>0.05). Compared with the control group and the PROM duration <72 hours group, the PROM duration ≥72 hours group had significantly higher incidence rates of pneumonia and intracranial hemorrhage in preterm infants; the PROM duration ≥72 hours group had a significantly higher incidence rate of congenital infection and a significantly longer mean length of hospital stay compared with the control group (P<0.05), while there were no significant differences between the PROM duration ≥72 hours group and the PROM duration <72 hours group (P>0.05). The multivariate analysis showed that PROM duration ≥72 hours was an independent risk factors for pneumonia (OR=2.200, 95%CI: 1.386-3.492) and intracranial hemorrhage (OR=2.331, 95%CI: 1.420-3.827) in preterm infants.</p><p><b>CONCLUSIONS</b>PROM duration ≥72 hours significantly increases the risk of placental infection in mothers and it is an independent risk factor for pneumonia and intracranial hemorrhage in preterm infants.</p>

Expression rhythm of autophagic gene in neurons of neonatal rats with hypoxia/ischemia and its regulatory mechanism / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the expression of autophagic gene and circadian gene in the neurons of neonatal rats after hypoxic-ischemic brain damage and the mechanism of nerve injury induced by hypoxia/ischemia.</p><p><b>METHODS</b>Twelve Sprague-Dawley (SD) rats were randomly divided into hypoxic-ischemic (HI) group and sham-operation group, with 6 rats in each group. Ligation of the right common carotid artery and hypoxic treatment were performed to establish a model of hypoxic-ischemic brain damage. Western blot was used to measure the expression of the circadian protein Clock in the cortex and hippocampus. The neurons of the rats were cultured in vitro and randomly divided into oxygen glucose deprivation (OGD) group and control group. The neurons in the OGD group were treated with DMEM medium without glucose or serum to simulate ischemic state, and hypoxic treatment was performed to establish an in vitro model of hypoxic-ischemic brain damage. Western blot was used to measure the expression of autophagy-related proteins Beclin1 and LC3 and Clock protein at different time points. The changes in the expression of Beclin1 and LC3 were measured after the expression of Clock protein in neurons was inhibited by small interfering RNA technique.</p><p><b>RESULTS</b>The expression of autophagy-related proteins Beclin1 and LC3Ⅱ in neurons cultured in vitro displayed a rhythmic fluctuation; after OGD treatment, the expression of Beclin1 and LC3Ⅱ gradually increased over the time of treatment and no longer had a rhythmic fluctuation. Compared with the sham-operation group, the HI group had a significant reduction in the expression of Clock protein in the cortex and hippocampus (P<0.05). After OGD treatment, the neurons cultured in vitro had a significant reduction in the expression of Clock protein (P<0.05). Compared with the negative control group, the Clock gene inhibition group had significant reductions in the expression of Beclin1 and LC3Ⅱ (P<0.05).</p><p><b>CONCLUSIONS</b>Hypoxia/ischemia induces the disorder in the expression rhythm of autophagy-related proteins Beclin1 and LC3, and the mechanism may be associated with the fact that the circadian protein Clock participates in the regulation of the expression of Beclin1 and LC3.</p>

Advances in genetic research of cerebral palsy / 中国当代儿科杂志

Cerebral palsy is a group of syndromes caused by non-progressive brain injury in the fetus or infant and can cause disabilities in childhood. Etiology of cerebral palsy has always been a hot topic for clinical scientists. More and more studies have shown that genetic factors are closely associated with the development of cerebral palsy. With the development and application of various molecular and biological techniques such as chromosome microarray analysis, genome-wide association study, and whole exome sequencing, new achievements have been made in the genetic research of cerebral palsy. Chromosome abnormalities, copy number variations, susceptibility genes, and single gene mutation associated with the development of cerebral palsy have been identified, which provides new opportunities for the research on the pathogenesis of cerebral palsy. This article reviews the advances in the genetic research on cerebral palsy in recent years.

Protective effect of histone acetylation against cortical injury in neonatal rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of histone acetylation against hypoxic-ischemic cortical injury in neonatal rats.</p><p><b>METHODS</b>A total of 90 neonatal rats aged 3 days were divided into three groups: sham-operation, cortical injury model, and sodium butyrate (a histone deacetylase inhibitor) treatment. The rats in the model and the sodium butyrate treatment groups were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg), and then right common carotid artery ligation was performed 2 hours later and the rats were put in a hypoxic chamber (oxygen concentration 6.5%) for 90 minutes. The rats in the sham-operation group were intraperitoneally injected with normal saline and the right common carotid artery was only separated and exposed without ligation or hypoxic treatment. The rats in the sodium butyrate treatment group were intraperitoneally injected with sodium butyrate (300 mg/kg) immediately after establishment of the cortical injury model once a day for 7 days. Those in the sham-operation and the model groups were injected with the same volume of normal saline. At 7 days after establishment of the model, Western blot was used to measure the protein expression of histone H3 (HH3), acetylated histone H3 (AH3), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (BAX), cleaved caspase-3 (CC3), and brain-derived neurotrophic factor (BDNF). Immunofluorescence assay was used to measure the expression of 5-bromo-2'-deoxyuridine (BrdU) as the cortex cell proliferation index.</p><p><b>RESULTS</b>The sodium butyrate treatment group had a significantly lower HH3/AH3 ratio than the model group (P<0.05), which suggested that the sodium butyrate treatment group had increased acetylation of HH3. Compared with the model group, the sodium butyrate treatment group had a significant increase in Bcl-2/Bax ratio, a significant reduction in CC3 expression, and a significant increase in BDNF expression (P<0.05). The sodium butyrate treatment group had a significant increase in the number of BrdU-positive cells in the cortex compared with the model group (P<0.05), and BrdU was mainly expressed in the neurons.</p><p><b>CONCLUSIONS</b>Increased histone acetylation may protect neonatal rats against cortical injury by reducing apoptosis and promoting regeneration of neurons. The mechanism may be associated with increased expression of BDNF.</p>

Effect of telomerase activation on biological behaviors of neural stem cells in rats with hypoxic-ischemic insults / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of telomerase activation on biological behaviors of neural stem cells after hypoxic-ischemic insults.</p><p><b>METHODS</b>The neural stem cells passaged in vitro were divided into four groups: control, oxygen-glucose deprivation (OGD), OGD+cycloastragenol (CAG) high concentration (final concentration of 25 μM), and OGD+CAG low concentration (final concentration of 10 μM). The latter three groups were subjected to OGD. Telomerase reverse transcriptase (TERT) expression level was evaluated by Western blot. Telomerase activity was detected by telomerase repeat amplification protocol (TRAP). Cell number and neural sphere diameter were measured under a microscope. The activity of lactate dehydrogenase (LDH) was examined by chemiluminescence. Cell proliferation rate and apoptosis were detected by flow cytometry.</p><p><b>RESULTS</b>After OGD insults, obvious injury of neural stem cells was observed, including less cell number, smaller neural sphere, more dead cells, lower proliferation rate and decreased survival rate. In CAG-treated groups, there were higher TERT expression level and telomerase activity compared with the control group (P<0.05). In comparison with the OGD group, CAG treatment attenuated cell loss (P<0.05) and neural sphere diameter decrease (P<0.05), promoted cell proliferation (P<0.05), and increased cell survival rate (P<0.05). Low and high concentrations of CAG had similar effects on proliferation and survival of neural stem cells (P>0.05). In the normal cultural condition, CAG treatment also enhanced TERT expression (P<0.05) and increased cell numbers (P<0.05) and neural sphere diameter (P<0.05) compared with the control group.</p><p><b>CONCLUSIONS</b>Telomerase activation can promote the proliferation and improve survival of neural stem cells under the state of hypoxic-ischemic insults, suggesting telomerase activators might be potential agents for the therapy of hypoxic-ischemic brain injury.</p>