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The role of regulatory B cells in immune regulation and childhood allergic asthma. 调节性 B 细胞在免疫调节和儿童过敏性哮喘中的作用。
Pub Date : 2024-01-04 DOI: 10.1186/s40348-023-00174-2
Caroline Vanessa Kliem, Bianca Schaub

Background: As the most common chronic disease in childhood, asthma displays a major public health problem worldwide with the incidence of those affected rising. As there is currently no cure for allergic asthma, it is mandatory to get a better understanding of the underlying molecular mechanism.

Main body: By producing IgE antibodies upon allergen contact, B cells play a pivotal role in allergic asthma. Besides that, IL-10-secreting B cell subsets, namely regulatory B cells (Bregs), are reported in mice and humans to play a role in allergic asthma. In humans, several Breg subsets with distinct phenotypic and functional properties are identified among B cells at different maturational and differentiation stages that exert anti-inflammatory functions by expressing several suppressor molecules. Emerging research has focused on the role of Bregs in allergic asthma as well as their role for future diagnostic and preventive strategies.

Conclusion: Knowledge about the exact function of human Bregs in allergic asthma is still very limited. This review aims to summarize the current knowledge on Bregs. We discuss different human Breg subsets, several ways of Breg induction as well as the mechanisms through which they exert immunoregulatory functions, and their role in (childhood) allergic asthma.

背景:作为儿童时期最常见的慢性疾病,哮喘是一个全球性的重大公共卫生问题,发病率不断上升。由于过敏性哮喘目前尚无根治方法,因此必须更好地了解其分子机制:通过在接触过敏原时产生 IgE 抗体,B 细胞在过敏性哮喘中起着关键作用。此外,据报道,在小鼠和人类中,分泌 IL-10 的 B 细胞亚群,即调节性 B 细胞(Bregs)在过敏性哮喘中发挥作用。在人类中,在处于不同成熟和分化阶段的 B 细胞中发现了几种具有不同表型和功能特性的 Breg 亚群,它们通过表达几种抑制分子来发挥抗炎功能。新的研究重点是 Bregs 在过敏性哮喘中的作用以及它们在未来诊断和预防策略中的作用:有关人类 Bregs 在过敏性哮喘中确切功能的知识仍然非常有限。本综述旨在总结目前有关 Bregs 的知识。我们讨论了不同的人类 Breg 亚群、Breg 诱导的几种方式及其发挥免疫调节功能的机制,以及它们在(儿童)过敏性哮喘中的作用。
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引用次数: 0
Phagocytic cell death leads to enhanced release of pro-inflammatory S100A12 in familial Mediterranean fever 吞噬细胞死亡导致家族性地中海热中促炎性 S100A12 的释放增强
Pub Date : 2023-12-13 DOI: 10.1186/s40348-023-00173-3
G. Varga, S. Schleifenbaum, U. Koenig, J. Waldkirch, C. Hinze, C. Kessel, W. Geluk, T. Pap, Elke Lainka, Tilmann Kallinich, D. Foell, H. Wittkowski
Familial Mediterranean fever (FMF) is a prototypical autoinflammatory syndrome associated with phagocytic cell activation. Pyrin mutations are the genetic basis of this disease, and its expression has been shown in monocytes, granulocytes, dendritic cells, and synovial fibroblasts. Pyrin functions as a cytosolic pattern recognition receptor and forms a distinct pyrin inflammasome. The phagocyte-specific protein S100A12 is predominantly expressed in granulocytes and belongs to the group of damage associated molecular patterns (DAMP). S100A12 can be detected at massively elevated levels in the serum of FMF patients, even in clinically inactive disease. Whether this is crucial for FMF pathogenesis is as yet unknown, and we therefore investigated the mechanisms of S100A12 release from granulocytes of FMF patients presenting clinically inactive. We demonstrate that FMF neutrophils from patients in clinical inactive disease possess an intrinsic activity leading to cell death even in exogenously unstimulated neutrophils. Cell death resembles NETosis and is dependent on ROS and pore forming protein gasdermin D (GSDMD), as inhibitors for both are capable of completely block cell death and S100A12 release. When pyrin-activator TcdA (Clostridium difficile toxin A) is used to stimulate, neutrophilic cell death and S100A12 release are significantly enhanced in neutrophils from FMF patients compared to neutrophils from HC. We are able to demonstrate that activation threshold of neutrophils from inactive FMF patients is decreased, most likely by pre-activated pyrin. FMF neutrophils present with intrinsically higher ROS production, when cultured ex vivo. This higher baseline ROS activity leads to increased GSDMD cleavage and subsequent release of, e.g., S100A12, and to increased cell death with features of NETosis and pyroptosis. We show for the first time that cell death pathways in neutrophils of inactive FMF patients are easily triggered and lead to ROS- and GSDMD-dependent activation mechanisms and possibly pathology. This could be therapeutically addressed by blocking ROS or GSDMD cleavage to decrease inflammatory outbreaks when becoming highly active.
家族性地中海热(FMF)是一种与吞噬细胞活化有关的典型自身炎症综合征。单核细胞、粒细胞、树突状细胞和滑膜成纤维细胞中都有 Pyrin 的表达。Pyrin 的功能是细胞膜模式识别受体,并形成一个独特的 pyrin 炎性体。吞噬细胞特异性蛋白 S100A12 主要在粒细胞中表达,属于损伤相关分子模式(DAMP)。在 FMF 患者的血清中可以检测到 S100A12 的大量升高,即使在临床上疾病并不活跃的情况下也是如此。因此,我们研究了临床表现不活跃的 FMF 患者粒细胞释放 S100A12 的机制。我们证明,临床非活动期患者的 FMF 中性粒细胞具有导致细胞死亡的内在活性,即使在外源性未刺激的中性粒细胞中也是如此。细胞死亡类似于NETosis,依赖于ROS和孔形成蛋白gasdermin D(GSDMD),因为两者的抑制剂都能完全阻止细胞死亡和S100A12的释放。当使用梭状芽孢杆菌毒素 A(pyrin-activator TcdA)进行刺激时,与 HC 中性粒细胞相比,FMF 患者中性粒细胞的中性粒细胞死亡和 S100A12 释放明显增强。我们能够证明,非活动性 FMF 患者中性粒细胞的活化阈值降低了,这很可能是由于预先激活了 pyrin。在体外培养时,FMF 嗜中性粒细胞会产生更多的 ROS。这种较高的基线 ROS 活性导致 GSDMD 裂解增加,随后释放出 S100A12 等物质,并导致细胞死亡增加,表现出 NETosis 和 pyroptosis 的特征。我们首次发现,非活动性 FMF 患者中性粒细胞的细胞死亡途径很容易被触发,并导致 ROS 和 GSDMD 依赖性激活机制,甚至可能导致病理变化。这可以通过阻断 ROS 或 GSDMD 的裂解来解决,从而在高度活跃时减少炎症爆发。
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引用次数: 0
Installation of the developing nephron in the fetal human kidney during advanced pregnancy. 妊娠晚期胎儿肾脏中正在发育的肾元的安装。
Pub Date : 2023-11-28 DOI: 10.1186/s40348-023-00172-4
Will W Minuth

Background: The kidneys of preterm and low birth weight babies reflect vulnerability, since several noxae can evoke the termination of nephron formation. This again leads to oligonephropathy with severe consequences for health in the later life. While the clinical parameters have been intensely investigated, only little is known about the initial traces left by the noxae. For the fetal human kidney, solely the lack of basophilic S-shaped bodies and the reduction in width of the nephrogenic zone were registered. It is not known in how far also the involved progenitor cells, the earlier nephron stages, the collecting duct (CD) ampullae, and the local interstitium are collaterally harmed.

Aim: The interstitium at the forming nephron is heterogeneously structured. Thereby, it fulfills quite different mastering and integrative tasks. Since data dealing with the installation of a nephron is not available, the microanatomical features were recorded.

Results: The microscopic specimens show that the installation of the transient stages of nephron anlage is not synchronized. Instead, it is controlled within a nephrogenic compartment of the nephrogenic zone. It starts near the renal capsule by positioning the nephrogenic niche so that the nephrogenic progenitor cells face the epithelial progenitor cell at the tip of a CD ampulla. Then, the induced nephrogenic progenitor cells assimilate in the pretubular aggregate. While its medial part remains opposite the head of the CD ampulla, at its proximal end, the primitive renal vesicle is formed. Only a part of it separates to stick to the section border between the head and conus of the CD ampulla. This marks the link with the future connecting tubule at the distal pole of the extending renal vesicle. Meanwhile, the proximal pole is mounted next to the connecting tubule of an earlier developed nephron. The resulting two-point mounting serves a common elongation of the conus at the CD ampulla and the medial aspect of the comma-shaped body. In the S-shaped body, it supports to defoliate the arising glomerulus and to link it with the perforating radiate artery at its deep lateral aspect.

Conclusions: The investigation depicts that the installation is an interactive process between the stages of nephron anlage and its structural neighbors. A special meaning has the interjacent interstitium. It is vital for the positioning, shaping, and physiological integration. Due to its special location, this is mainly exposed to noxae.

背景:早产儿和低出生体重儿的肾脏反映出脆弱性,因为一些因素可以引起肾元形成的终止。这再次导致少肾病,对晚年的健康造成严重后果。虽然临床参数已被深入研究,但对诺科菌留下的初始痕迹知之甚少。对于胎儿肾,仅记录到嗜碱性s形体的缺乏和肾源区宽度的减小。目前尚不清楚受累的祖细胞、早期肾元阶段、壶腹集管和局部间质在多大程度上也受到连带损害。目的:肾元形成处间质结构不均匀。因此,它完成了完全不同的掌握和综合任务。由于没有处理肾元安装的数据,因此记录了显微解剖特征。结果:显微标本显示肾元标本瞬态阶段的安装不同步。相反,它被控制在肾源区肾源室内。它从肾包膜附近开始,定位肾源性生态位,使肾源性祖细胞面对位于壶腹顶端的上皮祖细胞。然后,诱导的肾原性祖细胞在肾小管前聚集体中同化。虽然其内侧部分仍然相对于壶腹头部,但在其近端形成了原始肾小泡。它只有一部分分离,粘在CD壶腹头部和圆锥之间的截面边界上。这标志着与延伸的肾小泡远端未来连接小管的连接。同时,近极被安装在早期发育的肾元的连接小管旁边。由此产生的两点安装服务于在CD壶腹和逗号形体的内侧锥体的共同延伸。在s型体中,它支持起生肾小球的脱落,并在其深外侧将其与穿孔辐射动脉连接起来。结论:研究表明,肾元移植是肾元移植与其相邻结构阶段之间的相互作用过程。有一个特殊的意思是间质。它对定位、塑形和生理整合至关重要。由于其特殊的位置,它主要暴露在空气中。
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引用次数: 0
Gene therapy-based strategies for spinal muscular atrophy-an Asia-Pacific perspective. 以基因治疗为基础的脊髓性肌萎缩症治疗策略——亚太地区视角。
Pub Date : 2023-11-15 DOI: 10.1186/s40348-023-00171-5
Michelle A Farrar, Loudella Calotes-Castillo, Ranil De Silva, Peter Barclay, Lani Attwood, Julie Cini, Monica Ferrie, Didu S Kariyawasam

Onasemnogene abeparvovec has been life-changing for children with spinal muscular atrophy (SMA), signifying the potential and progress occurring in gene- and cell-based therapies for rare genetic diseases. Hence, it is important that clinicians gain knowledge and understanding in gene therapy-based treatment strategies for SMA. In this review, we describe the development and translation of onasemnogene abeparvovec from clinical trials to healthcare practice and share knowledge on the facilitators and barriers to implementation. Rapid and accurate SMA diagnosis, awareness, and education to safely deliver gene therapy to eligible patients and access to expertise in multidisciplinary management for neuromuscular disorders are crucial for health system readiness. Early engagement and intersectoral collaboration are required to surmount complex logistical processes and develop policy, governance, and accountability. The collection and utilisation of real-world evidence are also an important part of clinical stewardship, informing ongoing improvements to care delivery and access. Additionally, a research-enabled clinical ecosystem can expand scientific knowledge and discovery to optimise future therapies and magnify health impacts. Important ethical, equity, economic, and sustainability issues are evident, for which we must connect globally.

Onasemnogene abeparvovec已经改变了患有脊髓性肌萎缩症(SMA)的儿童的生活,标志着罕见遗传疾病的基因和细胞治疗的潜力和进展。因此,临床医生获得基于基因治疗的SMA治疗策略的知识和理解非常重要。在这篇综述中,我们描述了onasemnogene abparvovec从临床试验到医疗实践的发展和转化,并分享了实施的促进因素和障碍方面的知识。快速和准确的SMA诊断、意识和教育,以安全地向符合条件的患者提供基因治疗,以及获得神经肌肉疾病多学科管理方面的专业知识,对于卫生系统的准备至关重要。需要尽早参与和部门间合作,以克服复杂的后勤流程,制定政策、治理和问责制。收集和利用真实世界的证据也是临床管理的重要组成部分,为持续改进护理提供和获取提供信息。此外,以研究为导向的临床生态系统可以扩展科学知识和发现,以优化未来的治疗方法并扩大健康影响。重要的道德、公平、经济和可持续性问题是显而易见的,为此我们必须在全球范围内联系起来。
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引用次数: 0
Relevance and consequence of chronic inflammation for obesity development. 慢性炎症与肥胖发展的相关性和后果。
Pub Date : 2023-11-14 DOI: 10.1186/s40348-023-00170-6
Lisa Ruck, Susanna Wiegand, Peter Kühnen

Background: Increasing prevalence of morbid obesity accompanied by comorbidities like type 2 diabetes mellitus (T2DM) led to a demand for improving therapeutic strategies and pharmacological intervention options. Apart from genetics, inflammation processes have been hypothesized to be of importance for the development of obesity and related aspects like insulin resistance.

Main text: Within this review, we provide an overview of the intricate interplay between chronic inflammation of the adipose tissue and the hypothalamus and the development of obesity. Further understanding of this relationship might improve the understanding of the underlying mechanism and may be of relevance for the establishment of new treatment strategies.

背景:伴随2型糖尿病(T2DM)等合并症的病态肥胖的患病率日益增加,导致对改进治疗策略和药物干预选择的需求。除了遗传学,炎症过程被认为对肥胖和胰岛素抵抗等相关方面的发展很重要。在这篇综述中,我们概述了脂肪组织和下丘脑的慢性炎症与肥胖发展之间复杂的相互作用。进一步了解这种关系可能会提高对潜在机制的理解,并可能与建立新的治疗策略相关。
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引用次数: 0
B cell phenotype and serum levels of interferons, BAFF, and APRIL in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C). 新冠肺炎相关儿童多系统炎症综合征(MIS-C)中的B细胞表型和干扰素、BAFF和APRIL的血清水平。
Pub Date : 2023-10-28 DOI: 10.1186/s40348-023-00169-z
Adam Klocperk, Marketa Bloomfield, Zuzana Parackova, Ludovic Aillot, Jiri Fremuth, Lumir Sasek, Jan David, Filip Fencl, Aneta Skotnicova, Katerina Rejlova, Martin Magner, Ondrej Hrusak, Anna Sediva

Background: Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after the original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia, and activation of T cells with elevated IFN-γ. Observing the production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II, and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19.

Results: We documented a significant elevation of IFN-γ, but not IFN-α and IFN-λ in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the pre-IVIG presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients.

Conclusions: Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF.

背景:与新冠肺炎相关的儿童多系统炎症综合征(MIS-C)是儿科新冠肺炎的晚期并发症,无论其严重程度如何,都是在最初感染SARS-CoV-2数周后发生的。其特征是高炎症、中性粒细胞增多、淋巴细胞减少和IFN-γ升高的T细胞活化。观察自身抗体的产生以及与系统性自身免疫性疾病(如系统性红斑狼疮(SLE))的相似性,我们在COVID-19后的MIS-C患者和健康儿童队列中探讨了B细胞表型和I型、II型和III型干扰素的血清水平,以及细胞因子BAFF和APRIL。结果:我们记录了IFN-γ的显著升高,α和IFN-。在MIS-C患者血清中BAFF升高,并伴随着所有B细胞亚型上BAFFR表达的降低。与健康的新冠肺炎后儿童相比,患者的浆母细胞比例明显较低。我们注意到,在4/35名测试的MIS-C患者中,IVIG前存在ENA Ro60自身抗体。结论:我们的工作显示了体液免疫在MIS-C中的参与,并暗示了与SLE的病理生理学相似,BAFF升高会驱动自身反应性B细胞产生自身抗体。
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引用次数: 0
A novel serum calprotectin (MRP8/14) particle-enhanced immuno-turbidimetric assay (sCAL turbo) helps to differentiate systemic juvenile idiopathic arthritis from other diseases in routine clinical laboratory settings. 一种新的血清钙保护蛋白(MRP8/14)颗粒增强免疫比浊法(sCAL turbo)有助于在常规临床实验室环境中区分系统性幼年特发性关节炎和其他疾病。
IF 2.4 Q1 PEDIATRICS Pub Date : 2023-10-25 DOI: 10.1186/s40348-023-00168-0
Dirk Foell, Melanie Saers, Carolin Park, Ninna Brix, Mia Glerup, Christoph Kessel, Helmut Wittkowski, Claas Hinze, Lillemor Berntson, Anders Fasth, Charlotte Myrup, Ellen Nordal, Marite Rygg, Henrik Hasle, Birgitte Klug Albertsen, Troels Herlin, Dirk Holzinger, Christian Niederberger, Bernhard Schlüter

Background: Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings.

Methods: To evaluate the accuracy in identifying children with SJIA, the performance of a particle-enhanced immuno-turbidimetric assay for serum calprotectin (sCAL turbo) on an automated laboratory instrument was analyzed. Samples from 615 children were available with the diagnoses SJIA (n = 99), non-systemic JIA (n = 169), infections (n = 51), other inflammatory diseases (n = 126), and acute lymphoblastic leukemia (ALL, n = 147). In addition, samples from 23 healthy controls were included.

Results: The sCAL turbo assay correlated well with the MRP8/14 ELISA used in previous validation studies (r = 0.99, p < 0.001). It could reliably differentiate SJIA from all other diagnoses with significant accuracy (cutoff at 10,500 ng/ml, sensitivity 84%, specificity 94%, ROC area under curve 0.960, p < 0.001).

Conclusions: Serum calprotectin analyses are a helpful tool supporting the diagnosis of SJIA in children with prolonged fever or inflammatory disease. Here, we show that an immuno-turbidimetric assay for detection of serum calprotectin on an automated laboratory instrument can be implemented in clinical laboratory settings to facilitate its use as a diagnostic routine test in clinical practice.

背景:对有不明原因炎症症状的儿童进行鉴别诊断可能具有挑战性。特别是,将系统性幼年特发性关节炎(SJIA)与其他诊断区分开来是困难的。我们最近验证了骨髓相关蛋白8/14复合物(MRP8/14,也称为S100A8/A9复合物或血清钙卫蛋白)作为支持SJIA诊断的有用生物标志物。随后用商业ELISA对结果进行了确认。然而,分析技术的进一步优化对于确保其在常规实验室环境中大规模使用的可行性至关重要。方法:为了评估儿童SJIA的准确性,分析了在自动化实验室仪器上进行的血清钙卫蛋白颗粒增强免疫比浊法(sCAL-turbo)的性能。来自615名儿童的样本可用于诊断SJIA(n = 99),非系统性JIA(n = 169),感染(n = 51)、其他炎症性疾病(n = 126)和急性淋巴细胞白血病(ALL = 147)。此外,还包括来自23名健康对照的样本。结果:sCAL turbo法与以往验证研究中使用的MRP8/14 ELISA法具有良好的相关性(r = 0.99,p 结论:血清钙卫蛋白分析是支持诊断长期发热或炎症性疾病患儿SJIA的有用工具。在这里,我们表明,在自动化实验室仪器上检测血清钙卫蛋白的免疫浊度法可以在临床实验室环境中实施,以促进其在临床实践中作为诊断常规测试的使用。
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引用次数: 0
What do we know about the sleep effects of caffeine used to treat apnoea of prematurity? A systematic review of the literature. 我们对用于治疗早产儿呼吸暂停的咖啡因对睡眠的影响了解多少?对文献的系统综述。
Pub Date : 2023-09-18 DOI: 10.1186/s40348-023-00166-2
Ana Renata Pinto de Toledo, Higor Arruda Caetano, Jovito Adiel Skupien, Carina Rodrigues Boeck, Humberto Fiori, Rosane Souza da Silva

Objective: Scientific scrutiny has proved the safety and benefits of caffeine to treat apnoea of prematurity (AOP). However, there is no consensus on the effects of this treatment on sleep, especially considering the key role of adenosine and early brain development for sleep maturation. We systematically reviewed studies with sleep as a primary and/or secondary outcome or any mention of sleep parameters in the context of caffeine treatment for AOP.

Methods: We performed a systematic search of PubMed, Web of Science and the Virtual Health Library from inception to 7 September 2022 to identify studies investigating the short- and long-term effects of caffeine to treat AOP on sleep parameters. We used the PIC strategy considering preterm infants as the Population, caffeine for apnoea as the Intervention and no or other intervention other than caffeine as the Comparison. We registered the protocol on PROSPERO (CRD42021282536).

Results: Of 4019 studies, we deemed 20, including randomised controlled trials and follow-up and observational studies, to be eligible for our systematic review. The analysed sleep parameters, the evaluation phase and the instruments for sleep assessment varied considerably among the studies. The main findings can be summarised as follows: (i) most of the eligible studies in this systematic review indicate that caffeine used to treat AOP seems to have no effect on key sleep parameters and (ii) the effects on sleep when caffeine is administered earlier, at higher doses or for longer periods than the most common protocol have not been investigated. There is a possible correlation between the caffeine concentration and period of exposure and negative sleep quality, but the sleep assessment protocols used in the included studies did not have high-quality standards and could not provide good evidence.

Conclusions and implications: Sleep quality is an important determinant of health, and better investments in research with adequate sleep assessment tools are necessary to guarantee the ideal management of children who were born preterm.

目的:科学研究已经证明咖啡因治疗早产儿呼吸暂停(AOP)的安全性和益处。然而,对于这种治疗对睡眠的影响,尤其是考虑到腺苷和早期大脑发育对睡眠成熟的关键作用,目前还没有达成共识。我们系统地回顾了将睡眠作为主要和/或次要结果的研究,或在咖啡因治疗AOP的背景下提及睡眠参数的研究,从成立到2022年9月7日,科学网和虚拟健康图书馆确定了研究咖啡因治疗AOP对睡眠参数的短期和长期影响的研究。我们使用PIC策略,将早产儿作为人群,将咖啡因治疗呼吸暂停作为干预措施,并将除咖啡因以外的无干预或其他干预措施作为比较。我们在PROSPERO(CRD42021282536)上注册了该方案。结果:在4019项研究中,我们认为20项,包括随机对照试验、随访和观察性研究,符合我们的系统审查条件。所分析的睡眠参数、评估阶段和睡眠评估工具在不同的研究中差异很大。主要发现可总结如下:(i)本系统综述中的大多数合格研究表明,用于治疗AOP的咖啡因似乎对关键睡眠参数没有影响;(ii)与最常见的方案相比,更早、更高剂量或更长时间服用咖啡因对睡眠的影响尚未得到研究。咖啡因浓度、暴露时间和负睡眠质量之间可能存在相关性,但纳入研究中使用的睡眠评估方案没有高质量的标准,也无法提供良好的证据。结论和意义:睡眠质量是健康的重要决定因素,有必要更好地投资于具有足够睡眠评估工具的研究,以确保对早产儿童进行理想的管理。
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引用次数: 0
Retinopathy of prematurity: from oxygen management to molecular manipulation. 早产儿视网膜病变:从氧气管理到分子操作。
Pub Date : 2023-09-15 DOI: 10.1186/s40348-023-00163-5
Jonathan Woods, Susmito Biswas

Introduction: Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the premature retina with the potential to progress to extraretinal neovascularisation. This review serves as an introduction to retinopathy of prematurity (ROP), outlining key parts of ROP pathophysiology, diagnosis and treatment. ROP is traditionally diagnosed by indirect ophthalmoscopy and classified using anatomical zones, stages of disease, and the presence or absence of "plus disease" (dilation and tortuosity of the major retinal arterioles and venules). ROP has a bi-phasic pathophysiology: initial hyperoxia causes reduced retinal vascularisation, followed by pathological vaso-proliferation resulting from subsequent hypoxia and driven by vascular endothelial growth factor (VEGF).

Advancements in management: This review summarises previous trials to establish optimum oxygen exposure levels in newborns and more recently the development of anti-VEGF agents locally delivered to block pathological neovascularisation, which is technically easier to administer and less destructive than laser treatment.

Future directions: There remains an ongoing concern regarding the potential unwanted systemic effects of intravitreally administered anti-VEGF on the overall development of the premature baby. Ongoing dosing studies may lessen these fears by identifying the minimally effective dose required to block extraretinal neovascularisation.

简介:早产儿视网膜病变(ROP)是一种早产儿视网膜血管增殖性疾病,有可能发展为视网膜外新生血管。本文就早产儿视网膜病变(ROP)的病理生理、诊断和治疗的关键部分作一综述。传统上,ROP是通过间接眼科检查诊断的,并根据解剖区域、疾病分期和有无“附加疾病”(主要视网膜小动脉和小静脉的扩张和扭曲)进行分类。ROP具有双期病理生理:最初的高氧导致视网膜血管化减少,随后由血管内皮生长因子(VEGF)驱动的缺氧导致病理性血管增殖。管理方面的进展:本综述总结了以前在新生儿中建立最佳氧暴露水平的试验,以及最近局部递送抗vegf药物以阻断病理性新生血管的发展,这在技术上比激光治疗更容易管理且破坏性更小。未来方向:玻璃体内给药抗vegf对早产儿整体发育的潜在不良全身影响仍是一个持续关注的问题。正在进行的剂量研究可以通过确定阻断视网膜外新生血管所需的最低有效剂量来减轻这些担忧。
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引用次数: 0
Autoimmune lymphoproliferative immunodeficiencies (ALPID) in childhood: breakdown of immune homeostasis and immune dysregulation. 儿童自身免疫性淋巴增生性免疫缺陷(ALPID):免疫稳态的破坏和免疫失调。
Pub Date : 2023-09-13 DOI: 10.1186/s40348-023-00167-1
Vasil Toskov, Stephan Ehl

Many inborn errors of immunity (IEI) manifest with hallmarks of both immunodeficiency and immune dysregulation due to uncontrolled immune responses and impaired immune homeostasis. A subgroup of these disorders frequently presents with autoimmunity and lymphoproliferation (ALPID phenotype). After the initial description of the genetic basis of autoimmune lymphoproliferative syndrome (ALPS) more than 20 years ago, progress in genetics has helped to identify many more genetic conditions underlying this ALPID phenotype. Among these, the majority is caused by a group of autosomal-dominant conditions including CTLA-4 haploinsufficiency, STAT3 gain-of-function disease, activated PI3 kinase syndrome, and NF-κB1 haploinsufficiency. Even within a defined genetic condition, ALPID patients may present with staggering clinical heterogeneity, which makes diagnosis and management a challenge. In this review, we discuss the pathophysiology, clinical presentation, approaches to diagnosis, and conventional as well as targeted therapy of the most common ALPID conditions.

许多先天性免疫缺陷(IEI)表现为免疫缺陷和免疫失调的特征,由于不受控制的免疫反应和免疫稳态受损。这些疾病的一个亚组经常表现为自身免疫和淋巴细胞增生(ALPID表型)。在20多年前对自身免疫性淋巴细胞增生性综合征(ALPS)的遗传基础进行初步描述之后,遗传学的进展帮助确定了更多ALPID表型背后的遗传条件。其中,大多数是由一组常染色体显性疾病引起的,包括CTLA-4单倍不全、STAT3功能获得性疾病、活化PI3激酶综合征和NF-κB1单倍不全。即使在确定的遗传条件下,ALPID患者也可能表现出惊人的临床异质性,这使得诊断和管理成为一项挑战。在这篇综述中,我们讨论了最常见的ALPID的病理生理、临床表现、诊断方法、常规治疗和靶向治疗。
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引用次数: 0
期刊
Molecular and cellular pediatrics
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