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Resatorvid protects against hypoxic-ischemic brain damage in neonatal rats

Neural Regeneration Research 2020年第7期15卷 1316-1325页

作者： Li-Jun Jiang Zhen-Xing Xu Ming-Fu Wu Gai-Qin Dong Li-Li Zhang Jun-Yan Gao Chen-Xi Feng Xing Feng Department of neonatology Children's Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of neonatology Affiliated Hospital of Yangzhou UniversityYangzhouJiangsu ProvinceChina

Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still *** hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with ***,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic *** results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the ***,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling *** study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.

关键词： autophagy hypoxic-ischemic brain damage neonatal hypoxic-ischemic brain damage neuroinflammation nuclear factor kappa-B resatorvid TAK-242 Toll-like receptor 4

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Pathophysiology of periventricular leukomalacia:what we learned from animal models

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Neural Regeneration Research 2017年第11期12卷 1795-1796页

作者： Nahla Zaghloul Mohamed Ahmed neonatology division Pediatric DepartmentCohen Children's Medical Center at New YorkFeinstein Institute for Medical ResearchNorthwell Health SystemManhassetNYUSA Hofstra University HempsteadNYUSA

Periventricular leukomalacia （PVL）, a white matter injury （WMI） affecting the premature infant＇s brain is commonly associated with ce- rebral palsy （CP）. Among premature infants 〈 1,500 g, approximately 7,000 develop CP yearly and 20,000-30,000 exhibit major cognitive deficits yearly （Volpe, 2009）. PVL results from hypoxia-ischemia （HI） with or without infection and is characterized by white matter necrotic lesions, hypomyelination, microglial activation, astrogliosis, and neuronal death. Risk factors for the development of PVL include： prematurity associated with immature cerebrovascular development, HI insults with lack of appropriate auto-regulation of cerebral blood flow, free radical production, energy deprivation, intrauterine infec- tion and chorioamnionitis. Affected infants show definitive signs of cerebral palsy such as spastic diplegia, seizures, developmental delay, visual and hearing impairment, scoliosis and incontinence by 6-9 months of age. PVL can also occur in term infants with certain con- genital cyanotic heart disease which will not be our focus here （Volpe, 2001）.

关键词： Pathophysiology of periventricular leukomalacia nimal models

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Early Cardiac Catheterizations within 30 Days Post Congenital Heart Surgery in Children

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Congenital Heart Disease 2023年第1期18卷 79-95页

作者： Daniel Quandt Alessia Callegari Oliver Niesse Martin Christmann Anke Meinhold Hitendu Dave Walter Knirsch Oliver Kretschmar pediatric Heart Centre-Division of pediatric Cardiology University Children’s Hospital ZurichZurichSwitzerland Department neonatology and pediatric Intensive Care University Children’s Hospital ZurichZurichSwitzerland Department of Congenital Cardiothoracic Surgery University Children’s Hospital ZurichZurichSwitzerland Children’s Research Centre ZurichSwitzerlandUniversity Children’s Hospital ZurichZurichSwitzerland University of Zurich ZurichSwitzerland

Background:This study set out to assess the indications,feasibility,safety,and outcome of early cardiac catheterizations(CC)within 30 days after congenital heart surgery(CHS)in *** and Results:This is a retrospective,single-center case review study of all CC within 30 days after CHS between 1/2010-12/2020.A total of 317(138 diagnostic,179 interventional)CC were performed in 245 patients at a median of 4 days(IQR 13)after *** median age was 3 months(IQR 6),and body weight was 5 kg(IQR 4).A total of 194(61.2%)CC were performed in patients with univentricular *** revealed significant pathologies leading to early redo-surgery in 37 patients(12%).The transcatheter interventions primarily were needed in patients after cavo-pulmonary connection(n=69%,21.8%),right ventricle to pulmonary artery conduit(n=39%,12.3%),and Norwood-I surgery(n=34%,10.7%)presenting with hypoxemia,prolonged postoperative course,and suspected arterial stenosis on *** clinical impact of an early postoperative transcatheter intervention for the following clinical course was high in most *** were nine(2.8%)major and 20(6.3%)minor intra-procedural *** factor analysis revealed no difference for the occurrence of complications for patients’age,weight,and time from initial CHS,underlying *** heart disease,or ***:Early CC within 30 days after CHS in children can be performed safely with a high diagnostic and therapeutic *** rate of complications is low,while the therapeutic consequence is relevant.

关键词： Early postoperative cardiac catheterization congenital heart surgery children

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Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli

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World Journal of Gastroenterology 2008年第42期14卷 6564-6568页

作者： Xiao-Ming Ben Zong-Tai Feng Ya-Dong Lu Rui Chen Xiao-Yu Zhou Juan Li Sheng-Yun Shi Department of neonatology Nanjing Children's Hospital of Nanjing Medical University Nanjing 210008 Jiangsu Province China Department of pediatric Immunology Nanjing Children's Hospital of Nanjing Medical University Nanjing 210008 Jiangsu Province China pediatric Research Institute Nanjing Children's Hospital of Nanjing Medical University Nanjing 210008 Jiangsu Province China

AIM: To investigate the effect of a new infant formula supplemented with a low level (0.24 g/100 mL) of galacto-oligosaccharide (GOS) on intestinal micro-flora (Bif idobacteria, Lactobacilli and E. coli) and fermentation characteristics in term infants, compared with human milk and a standard infant formula without GOS. METHODS: Term infants (n = 371) were approached in this study in three hospitals of China. All infants started breast-feeding. Those who changed to formula-feeding within 4 wk after birth were randomly assigned to one of the two formula groups. Growth and stool characteristics, and side effects that occurred in recruited infants were recorded in a 3-mo follow-up period. Fecal samples were collected from a subpopulation of recruited infants for analysis of intestinal bacteria (culture technique), acetic acid (gas chromatography) and pH (indicator strip). RESULTS: After 3 mo, the intestinal Bifidobacteria, Lactobacilli , acetic acid and stool frequency were significantly increased, and fecal pH was decreased in infants fed with the GOS-formula or human milk, compared with those fed with the formula withoutGOS. No significant differences were observed between the GOS formula and human milk groups. Supplementation with GOS did not influence the incidence of crying, regurgitation and vomiting. CONCLUSION: A low level of GOS (0.24 g/100 mL) in infant formula can improve stool frequency, decrease fecal pH, and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk.

关键词： Human milk Prebiotic Probiotic Safety Chinese

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Temporal trends in inflammatory bowel disease publications over a 19-years period

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World Journal of Gastroenterology 2014年第44期20卷 16745-16749页

作者： Yael Weintraub Francis B Mimouni Shlomi Cohen pediatric Gastroenterology and Nutrition unit "Dana-Dwek" Children’s Hospital Tel Aviv Medical Center Sackler Faculty of Medicine Tel Aviv University Department of pediatrics "Dana-Dwek" Children’s Hospital Tel Aviv Medical Center and Sackler Faculty of Medicine Tel Aviv University Division of neonatology Shaare Zedek Medical Center

AIM: To determine whether temporal changes occurred in the pediatric vs adult inflammatory bowel disease(IBD), both in terms of number and type of yearly published ***:We aimed to evaluate all Pub Med-registered articles related to the field of IBD from January1,1993 and until December 31,*** searched for articles using the key words"inflammatory bowel disease"or"Crohn’s disease"or"ulcerative colitis"or"undetermined colitis",using the age filters of"child"or"adult".We repeated the search according to the total number per year of articles per type of article,for each year of the specified *** studied randomized controlled trials,clinical trials,case reports,meta-analyses,letters to the editor,reviews,systematic reviews,practice guidelines,and ***:We identified 44645 articles over the *** were 8687 pediatric-tagged articles vs 19750 adult-tagged *** 16208 articles were unaccounted and not assigned a"pediatric"or"adult"tag by Pub *** was an approximately3-fold significant increase in all articles recorded both in pediatric and adult *** significant increase was true for nearly every category of article but the number of clinical trials,meta-analysis,and randomized controlled trials increased proportionally more than the number of"lower quality"articles such as editorials or letters to the *** few guidelines were published every ***:There is a yearly linear increase in publications related to ***,there are more and more clinical trials and higher quality articles.

关键词： Inflammatory bowel disease Crohn's dis-ease Ulcerative colitis Randomized clinical trial Meta-analysis

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Familial hemophagocytic lymphohistiocytosis type 2 in a female Chinese neonate:A case report and review of the literature

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World Journal of Clinical Cases 2021年第21期9卷 6056-6066页

作者： Shao-Hua Bi Liang-Liang Jiang Li-Ying Dai Li-Li Wang Guang-Hui Liu Ru-Jeng Teng Division of neonatology Department of PediatricsThe First Affiliated Hospital of Anhui Medical UniversityHefei 230022Anhui ProvinceChina Department of neonatology Anhui Provincial Children's HospitalHefei 230022Anhui ProvinceChina Department of pediatric Neurology Anhui Provincial Children's HospitalHefei 230022Anhui ProvinceChina Department of pediatrics Medical College of WisconsinWauwatosaWI 53226United States

BACKGROUND Familial hemophagocytic lymphohistiocytosis type 2(FHL2)is a rare genetic disorder presenting with fever,hepatosplenomegaly,and pancytopenia secondary to perforin-1(PRF1)***2 has been described in Chinese but usually presents after 1 year *** describe a female Chinese neonate with FHL2 secondary to compound heterozygous PRF1 mutation with symptom onset before 1 mo *** review Chinese FHL2 patients in the literature for *** SUMMARY A 15-d-old female neonate was referred to our hospital for persistent fever and thrombocytopenia with diffuse *** was born to a G5P3 mother at 39 wk and 4 d via cesarean section secondary to breech *** resuscitation was required at *** was described to be very sleepy with poor appetite since *** developed a fever up to 39.5°C at 7 d of ***,anemia,and thrombocytopenia were detected at a local medical facility CONCLUSION A literature review identified 75 Chinese FHL2 patients,with only five presenting in the first year of *** and frameshift mutations are the most common PRF1 mutations in Chinese,with 24.8%having c.1349C>T followed by 11.6%having *** c.658G>C mutation has only been reported once in the literature and our case suggests it can be pathogenic,at least in the presence of another pathogenic mutation such as c.1066C>T.

关键词： Hemophagocytic lymphohistiocytosis Familial hemophagocytic lymphohistiocytosis Perforin-1 Neonate Compound heterozygous Case report

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新生儿缺氧缺血性脑病诊断标准

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中国当代儿科杂志 2005年第2期7卷 97-98页

作者：中华医学会儿科学分会新生儿学组 Subspecialty Group of neonatology Pediatric Society Chinese Medical Association China

新生儿缺氧缺血性脑病(HIE)是指围产期窒息导致脑的缺氧缺血性损害,临床出现一系列中枢神经异常的表现。其诊断根据临床表现,同时具备以下4条者可确诊,第4条暂时不能确定者可作为拟诊病例:①有明确的可导致胎儿宫内窘迫的异常产科病史,... 详细信息

新生儿缺氧缺血性脑病(HIE)是指围产期窒息导致脑的缺氧缺血性损害,临床出现一系列中枢神经异常的表现。其诊断根据临床表现,同时具备以下4条者可确诊,第4条暂时不能确定者可作为拟诊病例:①有明确的可导致胎儿宫内窘迫的异常产科病史,以及严重的胎儿宫内窘迫表现(胎心<100次,持续5min以上;和/或羊水III度污染),或者在分娩过程中有明显窒息史;②出生时有重度窒息,指Apgar评分1min≤3分,并延续至5min时仍≤5分;或者出生时脐动脉血气pH≤7. 00;③出生后不久出现神经系统症状、并持续至24h以上;④排除电解质紊乱、颅内出血和产伤等原因引起的抽搐,以及宫内感染、遗传代谢性疾病和其他先天性疾病所引起的脑损伤。本诊断标准仅适用于足月新生儿HIE的诊断。

关键词：诊断标准缺氧缺血,脑婴儿,新生

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Constitutive STAT3 phosphorylation and IL-6/IL-10 co-expression are associated with impaired T-cell function in tuberculosis patients

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Cellular & Molecular Immunology 2019年第3期16卷 275-287页

作者： Kirstin Harling Ernest Adankwah Alptekin Güler Anthony Afum-Adjei Awuah Louis Adu-Amoah Ertan Mayatepek Ellis Owusu-Dabo Norman Nausch Marc Jacobsen Department of General pediatrics Neonatologyand Pediatric CardiologyUniversity Children’s HospitalDuesseldorf 40225Germany Kumasi Centre for collaborative Research in Tropical Medicine(KCCR) KumasiGhana School of Public Health College of Health SciencesKwame Nkrumah University of Science and Technology(KNUST)KumasiGhana

T-cells critically contribute to protection against Mycobacterium tuberculosis infection,and impaired T-cell responses can lead to disease ***-inflammatory and immunosuppressive cytokines affect T-cells,and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell *** STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune *** characterized blood samples from tuberculosis patients(n=28)and healthy contacts(n=28)from Ghana for ***-specific T-cell responses,constitutive cytokine production,and SOCS3 and pSTAT3 *** modulation of primary CD4+T-cells was performed to determine the effects of SOCS3 on T-cell functions.T-cells from tuberculosis patients expressed higher levels of IL-10 and IL-6 and lower levels of T helper type(TH)17 cytokines after ***-specific stimulation compared to healthy *** addition,tuberculosis patients had higher IL-10 and IL-6 levels in the supernatants of non-stimulated immune cells and plasma samples compared to healthy ***,aberrant cytokine expression was accompanied by high constitutive pSTAT3 levels and SOCS3 expression in *** analysis identified an IL-6/IL-10 co-expression-based principal component in tuberculosis patients that correlated with high pSTAT3 ***3 contributed to a regulatory component,and tuberculosis patients with high SOCS3 expression showed decreased TH1 cytokine expression and impaired IL-2-induced STAT5 ***3 over-expression in primary CD4+T-cells confirmed the SOCS3 inhibitory function on IL-2-induced STAT5 *** conclude that constitutive pSTAT3 and high SOCS3 expression are influential factors that indicate impaired T-cell functions in tuberculosis patients.

关键词： tuberculosis Interleukin-6 Interleukin-10 STAT3 SOCS3

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Neonatal pneumothorax in congenital diaphragmatic hernia:Be wary of high ventilatory pressures

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World Journal of pediatric Surgery 2022年第3期5卷 154-161页

作者： Nathan Rubalcava Gabriella A Norwitz Aimee G Kim Gary Weiner Niki Matusko Meghan A Arnold George B Mychaliska Erin E Perrone pediatric Surgery University of MichiganAnn ArborMichiganUSA Section of neonatology Department of PediatricsUniversity of MichiganAnn ArborMichiganUSA Department of Surgery University of MichiganAnn ArborMichiganUSA

Background Patients with congenital diaphragmatic hernia(CDH)require invasive respiratory support and higher ventilator pressures may be associated with *** sought to evaluate the risk factors associated with pneumothorax in CDH neonates prior to *** Weretrospectivelyreviewednewborns born withCDHbetween 2014and 2019who developeda pneumothorax,and we matched these cases to patients with CDH without *** Twenty-sixpatientswere included(n=13per group).The pneumothorax group required extracorporeal life support(ECLS)more frequently(85%vs 54%,p=0.04),particularly among type A/B defects(31%vs 7%,p=0.01).The pneumothorax group had higher positive end-expiratory pressure(PEEP)within 1 hour of birth(p=0.02),at pneumothorax diagnosis(p=0.003),and at ECLS(p=0.02).The pneumothorax group had a higher mean airway pressure(Paw)at birth(p=0.01),within 1 hour of birth(p=0.01),and at pneumothorax diagnosis(p=0.04).Using multiple logistic regression with cluster robust SEs,higher Paw(OR 2.2,95%Cl 1.08 to 3.72,p=0.03)and PEEP(OR 1.8,95%CI 1.15 to 3.14,p=0.007)were associated with an increased risk of developing *** was no difference in survival(p=0.09).Conclusions Development of a pneumothorax in CDH neonates is independently associated with higher Paw and higher PEEP.A pneumothorax increases the likelihood of treated with ECLS,even with smaller defect.

关键词： PEEP pneumothorax diagnosis

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Management and outcomes of congenital chylothorax in the neonatal intensive care unit:A case series

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pediatric Investigation 2017年第1期1卷 21-25页

作者： Helen Healy Kevin Gipson Susanne Hay Sara Bates Thomas Bernard Kinane MassGeneral Hospital for Children BostonMAUSA Harvard Medical School BostonMAUSA pediatric Pulmonary Medicine MassGeneral Hospital for ChildrenBostonMAUSA Division of Newborn Medicine Boston Children’s HospitalBostonMAUSA neonatology and Newborn Medicine unit MassGeneral Hospital for ChildrenBostonMAUSA

Importance:Congenital chylothorax is a rare condition with pulmonary and multiorgan system effects,for which there are no standardized treatment *** review of known cases offers some conclusions and suggestions for ***:The aim of this study was to present a case series of 5 patients who were treated in the neonatal intensive care unit with ***:We describe 5 infants who were diagnosed prenatally with hydrops fetalis and postnatally had clinically significant congenital ***:Treatment guidelines specific to congenital forms of chylothorax have not yet been developed,although there are consistent trends across our *** of the 5 infants in this study have survived to *** was treated with chest tube placement and chylous fluid drainage,scrupulous attention to fluid balance,mechanical ventilation,and nutritional management and,in 3 cases,with octreotide *** of the infants also required treatment for immunodeficiency and altered coagulation *** of the infants underwent surgical thoracic duct ***:Aided by the advantage of prenatal diagnosis,many cases of congenital chylothorax can be successfully treated by a combination of nutritional and medical management as well as careful attention to fluid and electrolyte balance and avoidance of infection,thereby avoiding the need for surgical ligation of the thoracic duct.

关键词： congenital malformation evidence-based medicine&outcomes neonatal pulmonary medicine

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