
A New Global Definition of Acute Respiratory Distress Syndrome
文章来源:PubMed
摘要信息:Background. Since the 2012 Berlin Definition of the Acute Respiratory Distress Syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high flow nasal oxygen (HFNO), expanding use of pulse oximetry in place of arterial blood gases, use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods. A Consensus Conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021-March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would: (1) identify patients with the currently accepted conceptual framework for ARDS; (2) facilitate rapid ARDS diagnosis for clinical care and research; (3) be applicable in resource-limited settings; (4) be useful for testing specific therapies; and (5) be practical for communication to patients and caregivers. Results. The committee made four main recommendations: (1) Include HFNO with a minimum flow rate of 30 liters/min; (2) Use arterial oxygen tension (PaO2)/FiO2 300 mmHg or SpO2/FiO2 < 315 (if SpO2 97%) to identify hypoxemia; (3) Retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and (4) In resource-limited settings, do not require PEEP, oxygen flow rate, or specific respiratory support devices. Conclusions. We propose a New Global Definition of ARDS that builds on the Berlin Definition. The recommendations also identify areas for future research, including the need for prospective assessments of feasibility, reliability, and prognostic validity of the proposed Global Definition.

Population pharmacokinetics of sivelestat in Chinese patients with severe pneumonia(在中国重症肺炎患者中的群体药代动力学)
文章来源:PubMed
摘要信息:背景:缺血再灌注损伤(IRI)常导致肾脏损害。虽然中性粒细胞胞外陷阱(NETs)的存在一直被观察到,但它们对IRI的具体影响尚未确定。西维来司他钠是中性粒细胞弹性酶的抑制剂,对NET的形成至关重要,可能为肾脏IRI提供治疗方法,值得进一步研究。 方法:建立小鼠早期肾IRI模型,经损伤标志物和组织学检查证实。免疫荧光和Western blot证实NETs在肾I/R中的作用。通过一套全面的方法进一步评估肾功能和病理,包括周期性酸希夫染色(PAS)和末端脱氧核苷酸转移酶dUTP Nick末端标记(TUNEL)染色,酶联免疫吸附试验(ELISA),实时肾小球滤过率(RT-GFR)监测,聚合酶链反应(PCR),生化分析,以及额外的Western blot和免疫荧光试验。 结果:我们首先量化了肾IRI小鼠的NET表达,并在24小时达到峰值。随后,给予西维来司他钠治疗,导致MPO、CitH3降低,并减轻了肾小管损伤。此外,它还导致血清肌酐、血尿素氮(BUN)、中性粒细胞明胶酶相关脂钙蛋白(NGAL)和肾损伤分子-1 (KIM-1)水平降低。降低肾组织炎症标志物白介素-6 (IL-6)和肿瘤坏死因子-α (TNF-α)的丰度,减轻氧化应激指标丙二醛(MDA)和4羟基烯醛(4HNE)的水平,并伴有肾I/R小鼠肾细胞凋亡减少和GFR升高。 结论:西维来司他钠通过下调中性粒细胞NETs,减少炎症、氧化应激和细胞凋亡,从而改善肾IRI,从而增强肾功能。

Neutrophil Extracellular Traps Drive Kidney Stone Formation(中性粒细胞胞外陷阱驱动肾结石形成)
文章来源:PubMed
摘要信息:本研究旨在探讨中性粒细胞胞外陷阱 (NETs) 对肾结石的贡献。方法:来自GSE73680和生物信息学分析的微阵列数据用于鉴定肾结石患者的差异表达基因。通过乙二醇和氯化铵给药建立肾结石大鼠模型。采集血浆检测cf-DNA、DNase I、MPO-DNA、H3Cit、NE,生化分析检测超氧化物歧化酶、丙二醛、肌酐、血尿素氮、钙。免疫荧光染色检测肾组织中 MPO 、 H3Cit 和 NE 。通过 TUNEL 测定评估细胞凋亡。应用 HE 、 过碘酸-Schiff 和 Von Kossa 染色来确定肾脏中的组织学结构、钙沉积和结石形成。给予中性粒细胞弹性蛋白酶抑制剂 Sivelestat (SIVE) 抑制大鼠 NET。结果:在具有 Randall 斑块的肾组织和正常组织中共鉴定出 403 个差异表达基因,其中 270 个上调和 133 个下调基因。对这些失调的基因进行基因本体富集、KEGG 通路和蛋白质-蛋白质相互作用网络分析。此外,在肾结石患者中观察到 NET 标志物增加,包括 cf-DNA 、 DNase I、MPO-DNA 、 H3Cit 和 NE 以及钙沉积物。随后,我们建立了肾结石大鼠模型。我们发现肾结石大鼠 NET 形成显著升高,随着肾结石的发展,肾小管损伤和凋亡细胞增强。引人注目的是,我们发现通过 SIVE 抑制 NETs 可以显着减少钙沉积和凋亡细胞,减轻肾小管损伤,从而改善肾功能。结论:NETs 会促进肾结石的形成,从而加重肾损伤。我们的研究将 NETs 确定为肾结石的潜在诊断和治疗生物标志物。