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Functional analysis of granulocyte and monocyte subpopulations in neonates 新生儿粒细胞和单核细胞亚群的功能分析
Q1 PEDIATRICS Pub Date : 2019-11-28 DOI: 10.1186/s40348-019-0092-y
I. Hegge, Ferry Niepel, A. Lange, A. Vogelgesang, M. Heckmann, J. Ruhnau
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引用次数: 9
Vitamin D supplementation after the second year of life: joint position of the Committee on Nutrition, German Society for Pediatric and Adolescent Medicine (DGKJ e.V.), and the German Society for Pediatric Endocrinology and Diabetology (DGKED e.V.). 2岁后补充维生素D:营养委员会、德国儿科和青少年医学学会(DGKJ e.v.)和德国儿科内分泌学和糖尿病学会(DGKED e.v.)的联合立场。
Q1 PEDIATRICS Pub Date : 2019-05-06 DOI: 10.1186/s40348-019-0090-0
Thomas Reinehr, Dirk Schnabel, Martin Wabitsch, Susanne Bechtold-Dalla Pozza, Christoph Bührer, Bettina Heidtmann, Frank Jochum, Thomas Kauth, Antje Körner, Walter Mihatsch, Christine Prell, Silvia Rudloff, Bettina Tittel, Joachim Woelfle, Klaus-Peter Zimmer, Berthold Koletzko

Background: Low vitamin D serum concentrations have been associated with rickets and other disorders in observational studies. Since vitamin D serum concentrations in children and adolescents are frequently below reference values, it is debated whether vitamin D should be supplemented after infancy.

Methods: The effects of vitamin D supplementation in children > 2 years of age are analyzed based on a literature review of randomized controlled trials (RCTs).

Results: Vitamin D supplementation can potentially reduce the risk for influenza infections and improve asthma bronchiale exacerbation; however, it has no impact on asthma bronchiale severity. Vitamin D supplementation has no relevant effect on attention-deficit/hyperactivity disorders, cardiac failure, hypertension, or incidence of type II diabetes mellitus. Vitamin D supplementation has no effect on the rate of multiple sclerosis relapses, but on the number of new lesions detected by MRI. For other endpoints, RCTs are lacking.

Conclusion: Based on currently available studies, routine vitamin D supplementation is not be recommended for children aged > 2 years, even when they have serum concentrations below reference values. Routine vitamin D supplementation is not recommended in children who do not have risk factors and chronic diseases which are associated with calcium or vitamin D resorption disorders.

背景:在观察性研究中,低维生素D血清浓度与佝偻病和其他疾病有关。由于儿童和青少年的维生素D血清浓度经常低于参考值,因此在婴儿期后是否应该补充维生素D一直存在争议。方法:通过随机对照试验(RCTs)的文献综述,分析维生素D补充剂对> 2岁儿童的影响。结果:补充维生素D可以潜在地降低流感感染的风险,改善哮喘支气管恶化;然而,它对支气管哮喘的严重程度没有影响。补充维生素D对注意缺陷/多动障碍、心力衰竭、高血压或II型糖尿病的发病率没有相关影响。补充维生素D对多发性硬化症的复发率没有影响,但对MRI检测到的新病变数量有影响。对于其他终点,缺乏随机对照试验。结论:根据现有的研究,不建议2岁以上的儿童常规补充维生素D,即使他们的血清浓度低于参考值。对于没有与钙或维生素D吸收障碍相关的危险因素和慢性疾病的儿童,不建议常规补充维生素D。
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引用次数: 13
Complementary foods in baby food pouches: position statement from the Nutrition Commission of the German Society for Pediatrics and Adolescent Medicine (DGKJ, e.V.). 婴儿食品袋中的辅食:德国儿科和青少年医学学会营养委员会(DGKJ, e.v.)的立场声明。
Q1 PEDIATRICS Pub Date : 2019-03-06 DOI: 10.1186/s40348-019-0089-6
Berthold Koletzko, Christoph Bührer, Regina Ensenauer, Frank Jochum, Hermann Kalhoff, Burkhard Lawrenz, Antje Körner, Walter Mihatsch, Silvia Rudloff, Klaus-Peter Zimmer

Pureed complementary feeding products packed in squeezable plastic pouches, usually with a spout and a screw cap, have been increasingly marketed. The Committee on Nutrition recommends that infants and young children should not suck pureed or liquid complementary foods from baby food pouches. Complementary foods should be offered with a spoon or should be fed as finger foods. Infants and young children should be given the opportunity to get to know a variety of foods and food textures including pieces of foods, supported by responsive feeding between the child and their parents or caregivers. Complementary foods marketed in baby food pouches often have a high energy density and are predominantly extremely high in sugar content, with up to almost 90% of the total energy content. Regular consumption bears the risks of imbalanced nutrient provision and increased risks for dental caries and overweight. Complementary foods for infants and young children should have a balanced composition following the recommendations of the German Society of Pediatrics and Adolescent Medicine (DGKJ) and should contain only limited amounts of sugar. We discourage the feeding of pureed complementary foods from baby food pouches.

糊状辅食产品包装在可挤压的塑料袋,通常有一个喷嘴和一个螺旋盖,已经越来越多地推向市场。营养委员会建议,婴幼儿不应从婴儿食品袋中吮吸浆糊或液体辅食。辅食应该用勺子提供,或者应该作为手指食物来喂。婴儿和幼儿应该有机会了解各种食物和食物质地,包括食物的碎片,并通过儿童与其父母或照顾者之间的反应性喂养来支持。在婴儿食品袋中销售的辅食通常具有高能量密度,主要是极高的糖含量,几乎占总能量含量的90%。经常食用会带来营养供应不平衡的风险,增加患龋齿和超重的风险。婴儿和幼儿的辅食应按照德国儿科和青少年医学协会(DGKJ)的建议,具有均衡的成分,并且应只含有有限数量的糖。我们不鼓励从婴儿食品袋中喂养泥状辅食。
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引用次数: 28
KUNO-Kids birth cohort study: rationale, design, and cohort description. kuno -儿童出生队列研究:基本原理、设计和队列描述。
Q1 PEDIATRICS Pub Date : 2019-01-09 DOI: 10.1186/s40348-018-0088-z
Susanne Brandstetter, Antoaneta A Toncheva, Jakob Niggel, Christine Wolff, Silvia Gran, Birgit Seelbach-Göbel, Christian Apfelbacher, Michael Melter, Michael Kabesch

Background: Birth cohort studies can contribute substantially to the understanding of health and disease - in childhood and over the life course. The KUNO-Kids birth cohort study was established to investigate various aspects of child health, using novel omics technologies in a systems medicine approach.

Results: After 3 years of recruitment, 2515 infants and their families have joined the study. Parents with higher education are overrepresented as in many other birth cohorts and are more likely to complete follow-up assessments via self-report questionnaires. The vast majority of participants consented to clinical examinations of their child and to the non-invasive collection of diverse biosamples, which were processed specifically for their integrated use in omics technology covering genomics, epigenomics, transcriptomics, metabolomics, and microbiome analyses of the skin, oral cavity, and stool.

Conclusions: The data and diverse biomaterial collected in the KUNO-Kids birth cohort study will provide extensive opportunities for investigating child health and its determinants in a holistic approach. The combination of a broad range of research questions in one study will allow for a cost-effective use of biomaterial and omics results and for a comprehensive analysis of biological and social determinants of health and disease. Aiming for low attrition and ensuring participants' long-term commitment will be crucial to fully exploit the potential of the study.

背景:出生队列研究可以大大有助于了解儿童时期和整个生命过程中的健康和疾病。KUNO-Kids出生队列研究的建立是为了调查儿童健康的各个方面,在系统医学方法中使用新的组学技术。结果:经过3年的招募,2515名婴儿及其家庭加入了研究。与许多其他出生队列一样,受过高等教育的父母比例过高,而且更有可能通过自我报告问卷完成后续评估。绝大多数参与者同意对他们的孩子进行临床检查,并非侵入性地收集各种生物样本,这些样本经过专门处理,用于组学技术的综合应用,包括基因组学、表观基因组学、转录组学、代谢组学和皮肤、口腔和粪便的微生物组学分析。结论:在KUNO-Kids出生队列研究中收集的数据和各种生物材料将为以整体方法调查儿童健康及其决定因素提供广泛的机会。在一项研究中结合广泛的研究问题,将能够以具有成本效益的方式利用生物材料和组学结果,并对健康和疾病的生物和社会决定因素进行全面分析。以低流失率为目标,确保参与者的长期投入,将是充分利用研究潜力的关键。
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引用次数: 37
Gene correction of HBB mutations in CD34+ hematopoietic stem cells using Cas9 mRNA and ssODN donors. 使用Cas9 mRNA和ssODN供体对CD34+造血干细胞HBB突变进行基因校正。
Q1 PEDIATRICS Pub Date : 2018-11-14 DOI: 10.1186/s40348-018-0086-1
Justin S Antony, Ngadhnjim Latifi, A K M Ashiqul Haque, Andrés Lamsfus-Calle, Alberto Daniel-Moreno, Sebastian Graeter, Praveen Baskaran, Petra Weinmann, Markus Mezger, Rupert Handgretinger, Michael S D Kormann

Background: β-Thalassemia is an inherited hematological disorder caused by mutations in the human hemoglobin beta (HBB) gene that reduce or abrogate β-globin expression. Although lentiviral-mediated expression of β-globin and autologous transplantation is a promising therapeutic approach, the risk of insertional mutagenesis or low transgene expression is apparent. However, targeted gene correction of HBB mutations with programmable nucleases such as CRISPR/Cas9, TALENs, and ZFNs with non-viral repair templates ensures a higher safety profile and endogenous expression control.

Methods: We have compared three different gene-editing tools (CRISPR/Cas9, TALENs, and ZFNs) for their targeting efficiency of the HBB gene locus. As a proof of concept, we studied the personalized gene-correction therapy for a common β-thalassemia splicing variant HBBIVS1-110 using Cas9 mRNA and several optimally designed single-stranded oligonucleotide (ssODN) donors in K562 and CD34+ hematopoietic stem cells (HSCs).

Results: Our results exhibited that indel frequency of CRISPR/Cas9 was superior to TALENs and ZFNs (P < 0.0001). Our designed sgRNA targeting the site of HBBIVS1-110 mutation showed indels in both K562 cells (up to 77%) and CD34+ hematopoietic stem cells-HSCs (up to 87%). The absolute quantification by next-generation sequencing showed that up to 8% site-specific insertion of the NheI tag was achieved using Cas9 mRNA and a chemically modified ssODN in CD34+ HSCs.

Conclusion: Our approach provides guidance on non-viral gene correction in CD34+ HSCs using Cas9 mRNA and chemically modified ssODN. However, further optimization is needed to increase the homology directed repair (HDR) to attain a real clinical benefit for β-thalassemia.

背景:β-地中海贫血是一种遗传性血液学疾病,由人血红蛋白β (HBB)基因突变导致β-珠蛋白表达减少或消除引起。虽然慢病毒介导的β-珠蛋白表达和自体移植是一种很有前景的治疗方法,但插入突变或低转基因表达的风险是显而易见的。然而,使用可编程核酸酶(如CRISPR/Cas9、TALENs和ZFNs)和非病毒修复模板对HBB突变进行靶向基因校正可确保更高的安全性和内源性表达控制。方法:我们比较了三种不同的基因编辑工具(CRISPR/Cas9、TALENs和ZFNs)对HBB基因位点的靶向效率。为了证明这一概念,我们研究了在K562和CD34+造血干细胞(hsc)中使用Cas9 mRNA和几种优化设计的单链寡核苷酸(ssODN)供体对常见的β-地中海贫血剪接变体HBBIVS1-110的个性化基因校正治疗。结果:我们的研究结果显示,CRISPR/Cas9的indel频率优于TALENs和ZFNs (P IVS1-110突变在K562细胞(高达77%)和CD34+造血干细胞- hsc(高达87%)中均显示indel。下一代测序的绝对定量显示,在CD34+ hsc中,使用Cas9 mRNA和化学修饰的ssODN可实现高达8%的NheI标签位点特异性插入。结论:我们的方法为利用Cas9 mRNA和化学修饰的ssODN对CD34+造血干细胞进行非病毒基因校正提供了指导。然而,需要进一步优化以增加同源定向修复(HDR)以获得β-地中海贫血的真正临床益处。
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引用次数: 43
Chemotherapy and the pediatric brain. 化疗和儿童大脑。
Q1 PEDIATRICS Pub Date : 2018-11-06 DOI: 10.1186/s40348-018-0087-0
Chrysanthy Ikonomidou

Survival rates of children with cancer are steadily increasing. This urges our attention to neurocognitive and psychiatric outcomes, as these can markedly influence the quality of life of these children. Neurobehavioral morbidity in childhood cancer survivors affects diverse aspects of cognitive function, which can include attention, memory, processing speed, intellect, academic achievement, and emotional health. Reasons for neurobehavioral morbidity are multiple with one major contributor being chemotherapy-induced central nervous system (CNS) toxicity. Clinical studies investigating the effects of chemotherapy on the CNS in children with cancer have reported causative associations with the development of leukoencephalopathies as well as smaller regional grey and white matter volumes, which have been found to correlate with neurocognitive deficits.Preclinical work has provided compelling evidence that chemotherapy drugs are potent neuro- and gliotoxins in vitro and in vivo and can cause brain injury via excitotoxic and apoptotic mechanisms. Furthermore, chemotherapy triggers DNA (deoxyribonucleic acid) damage directly or through increased oxidative stress. It can shorten telomeres and accelerate cell aging, cause cytokine deregulation, inhibit hippocampal neurogenesis, and reduce brain vascularization and blood flow. These mechanisms, when allowed to operate on the developing brain of a child, have high potential to not only cause brain injury, but also alter crucial developmental events, such as myelination, synaptogenesis, neurogenesis, cortical thinning, and formation of neuronal networks.This short review summarizes key publications describing neurotoxicity of chemotherapy in pediatric cancers and potential underlying pathomechanisms.

儿童癌症患者的存活率正在稳步上升。这促使我们关注神经认知和精神方面的结果,因为这些会显著影响这些儿童的生活质量。儿童癌症幸存者的神经行为疾病影响认知功能的各个方面,包括注意力、记忆力、处理速度、智力、学业成就和情绪健康。神经行为发病的原因是多种多样的,其中一个主要原因是化疗引起的中枢神经系统(CNS)毒性。临床研究调查了化疗对癌症儿童中枢神经系统的影响,报告了与白质脑病的发展以及区域灰质和白质体积较小的因果关系,这与神经认知缺陷有关。临床前工作提供了令人信服的证据,表明化疗药物在体内和体外都是强效的神经和胶质毒素,并可通过兴奋毒性和细胞凋亡机制引起脑损伤。此外,化疗直接或通过增加氧化应激触发DNA(脱氧核糖核酸)损伤。它可以缩短端粒,加速细胞老化,引起细胞因子失调,抑制海马神经发生,减少脑血管和血液流动。这些机制,当被允许在儿童发育中的大脑上进行操作时,不仅有可能导致脑损伤,而且还可能改变关键的发育事件,如髓鞘形成、突触发生、神经发生、皮质变薄和神经元网络的形成。这篇简短的综述总结了描述化疗在儿童癌症中的神经毒性和潜在的潜在病理机制的主要出版物。
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引用次数: 34
The role of S100 proteins in the pathogenesis and monitoring of autoinflammatory diseases. S100蛋白在自身炎症性疾病发病机制和监测中的作用。
Q1 PEDIATRICS Pub Date : 2018-09-25 DOI: 10.1186/s40348-018-0085-2
Dirk Holzinger, Dirk Foell, Christoph Kessel

S100A8/A9 and S100A12 are released from activated monocytes and granulocytes and act as proinflammatory endogenous toll-like receptor (TLR)4-ligands. S100 serum concentrations correlate with disease activity, both during local and systemic inflammatory processes. In some autoinflammatory diseases such as familial Mediterranean fever (FMF) or systemic juvenile idiopathic arthritis (SJIA), dysregulation of S100 release may be involved in the pathogenesis. Moreover, S100 serum levels are a valuable supportive tool in the diagnosis of SJIA in fever of unknown origin. Furthermore, S100 levels can be used to monitor disease activity to subclinical level, as their serum concentrations decrease with successful treatment.

S100A8/A9和S100A12从活化的单核细胞和粒细胞中释放,作为促炎内源性toll样受体(TLR)4配体。在局部和全身炎症过程中,血清S100浓度与疾病活动性相关。在一些自身炎症性疾病,如家族性地中海热(FMF)或系统性青少年特发性关节炎(SJIA)中,S100释放的失调可能参与了发病机制。此外,血清S100水平是诊断不明原因发热中SJIA的宝贵支持工具。此外,S100水平可用于监测疾病活动至亚临床水平,因为其血清浓度随着治疗成功而降低。
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引用次数: 36
Precision medicine in pediatric oncology. 儿科肿瘤学的精准医学。
Q1 PEDIATRICS Pub Date : 2018-08-31 DOI: 10.1186/s40348-018-0084-3
Stefan E G Burdach, Mike-Andrew Westhoff, Maximilian Felix Steinhauser, Klaus-Michael Debatin

Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric oncology with a special focus on targeted drug therapies like kinase inhibitors and inducers of apoptosis, the impact of cancer genome sequencing and immunotherapy.

自20世纪70年代以来,儿童癌症的治疗效果有了显著改善。这一成功在很大程度上是由于实施了标准化和发展儿童癌症治疗的合作临床研究试验组。然而,某些类型的恶性肿瘤的结果仍然是不利的。以急性和长期副作用为代价,常规化疗和放疗的强化只能略微改善预后。因此,有必要制定针对性的治疗策略。在此,我们回顾了儿科肿瘤精准医学的发展和前景,特别关注激酶抑制剂和细胞凋亡诱导剂等靶向药物治疗,癌症基因组测序和免疫治疗的影响。
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引用次数: 25
Anti-inflammatory monocytes-interplay of innate and adaptive immunity. 抗炎单核细胞--先天性免疫和适应性免疫的相互作用。
Q1 PEDIATRICS Pub Date : 2018-04-03 DOI: 10.1186/s40348-018-0083-4
Georg Varga, Dirk Foell

Monocytes are central to our health as they contribute to both hemispheres of our immune system, the innate and the adaptive arm. Sensing signals from the outside world, monocytes govern the innate immunity by initiating inflammation, e.g., through production of IL-1β. Uncontrolled and sustained inflammation, however, leads to auto-inflammatory syndromes and sometimes to autoimmune diseases. Monocytes can be a driving force for the establishment of such diseases when their ability to also contribute to the resolution of inflammation is impaired. It is therefore of vast importance to gain knowledge about the anti-inflammatory mechanisms monocytes can use to participate in downregulation and resolution of inflammation. Here, we summarize some of the known anti-inflammatory mechanisms and features of regulatory monocytes and shed light on their importance in governing innate and adaptive immune responses. Considering anti-inflammatory mechanisms of monocytes will also help to develop new strategies to use monocytes as therapeutic targets in the future.

单核细胞对我们的健康至关重要,因为它们对免疫系统的两个半球--先天性免疫系统和适应性免疫系统--都有贡献。单核细胞感受到来自外界的信号后,会通过产生 IL-1β 等方式引发炎症,从而控制先天性免疫。然而,不受控制的持续炎症会导致自身炎症综合征,有时甚至会引发自身免疫性疾病。当单核细胞解决炎症的能力受损时,它们就会成为导致此类疾病的驱动力。因此,了解单核细胞参与下调和消除炎症的抗炎机制非常重要。在此,我们总结了调节性单核细胞的一些已知抗炎机制和特征,并阐明了它们在先天性和适应性免疫反应中的重要性。考虑单核细胞的抗炎机制还将有助于开发新的策略,在未来将单核细胞用作治疗靶点。
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引用次数: 0
Intrauterine growth restriction - impact on cardiovascular diseases later in life. 宫内生长限制-对以后生活中心血管疾病的影响。
Q1 PEDIATRICS Pub Date : 2018-03-20 DOI: 10.1186/s40348-018-0082-5
Carlos Menendez-Castro, Wolfgang Rascher, Andrea Hartner

Intrauterine growth restriction (IUGR) is a fetal pathology which leads to increased risk for certain neonatal complications. Furthermore, clinical and experimental studies revealed that IUGR is associated with a significantly higher incidence of metabolic, renal and cardiovascular diseases (CVD) later in life. One hypothesis for the higher risk of CVD after IUGR postulates that IUGR induces metabolic alterations that then lead to CVD.This minireview focuses on recent studies which demonstrate that IUGR is followed by early primary cardiovascular alterations which may directly progress to CVD later in life.

宫内生长受限(IUGR)是一种胎儿病理,导致某些新生儿并发症的风险增加。此外,临床和实验研究表明,IUGR与生命后期代谢、肾脏和心血管疾病(CVD)的发生率显著升高有关。关于IUGR后CVD风险增加的一个假设是,IUGR诱导代谢改变,从而导致CVD。这篇综述主要关注最近的研究,这些研究表明IUGR之后是早期原发性心血管改变,这些改变可能在以后的生活中直接发展为CVD。
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引用次数: 42
期刊
Molecular and cellular pediatrics
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