In the event of a mass casualty radiation scenario, rapid assessment of patients' health and triage is required for optimal resource utilization. Identifying the level and extent of exposure as well as prioritization of care is extremely challenging under such disaster conditions. Blood-based biomarkers, such as RNA integrity numbers (RIN), could help healthcare personnel quickly and efficiently determine the extent and effect of multiple injuries on patients' health. Evaluation of the effect of different radiation doses, alone or in combination with burn injury, on total RNA integrity over multiple time points was performed. Total RNA integrity was tallied in blood samples for potential application as a marker of radiation exposure and survival. Groups of aged mice (3-6 mice/group, 13-18 months old) received 0.5, 1, 5, 10 or 20 Gy ionizing radiation. Two additional mouse groups received low-dose irradiation (0.5 or 1 Gy) with a 15% total body surface area (TBSA) burn injury. Animals were euthanized at 2 or 12 h and at day 1, 2, 3, 7 or 14 postirradiation, or when injury-mediated mortality occurred. Total RNA was isolated from blood. The quality of RNA was evaluated and RNA RIN were obtained. Analysis of RIN indicated that blood showed the clearest radiation effect. There was a time- and radiation-dose-dependent reduction in RIN that was first detectable at 12 h postirradiation for all doses in animals receiving irradiation alone. This effect was reversible in lower-dose groups (i.e., 0.5, 1 and 5 Gy) that survived to the end of the study (14 days). In contrast, the effect persisted for 10 and 20 Gy groups, which showed suppression of RIN values <4.5 with high mortalities. Radiation doses of 20 Gy were lethal and required euthanasia by day 6. A low RIN (<2.5) at any time point was associated with 100% mortality. Combined radiation-burn injury produced significantly increased mortality such that no dually-injured animals survived beyond day 3, and no radiation dose >1 Gy resulted in survival past day 1. More modest suppression of RIN was observed in the surviving dually challenged mice, and no statistically significant changes were identified in RIN values of burn-only mice at any time point. In this study of an animal model, a proof of concept is presented for a simple and accurate method of assessing radiation dose exposure in blood which potentially predicts lethality. RIN assessment of blood-derived RNA could form the basis for a clinical decision-support tool to guide healthcare providers under the strenuous conditions of a radiation-based mass casualty event.

中文翻译：

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血液RNA完整性是放射线暴露和预后的直接而简单的报告者：一项初步研究。

在发生大量人员伤亡的情况下，需要对患者的健康状况和分类进行快速评估，以优化资源利用。在这样的灾难条件下，确定暴露的水平和程度以及护理的优先次序是极具挑战性的。RNA完整性数字（RIN）等基于血液的生物标志物可以帮助医护人员快速有效地确定多种伤害对患者健康的程度和影响。在多个时间点评估了不同辐射剂量（单独或与烧伤结合使用）对总RNA完整性的影响。计算出血液样本中的总RNA完整性，可作为放射线暴露和存活的标志物。老年小鼠组（3-6只小鼠/组，13-18个月大）接受0.5、1、5，10或20 Gy电离辐射。另外两个小鼠组接受了低剂量照射（0.5或1 Gy），总表面积（TBSA）为15％烧伤。在放疗后2或12小时和第1、2、3、7或14天或发生伤害介导的死亡率时对动物实施安乐死。从血液中分离出总RNA。评价RNA的质量并获得RNA RIN。RIN分析表明，血液显示出最清晰的辐射作用。在首次接受辐照的动物中，所有剂量的RIN随时间和辐照剂量的降低都首先在辐照后12小时被检测到。在存活至研究结束（14天）的小剂量组（即0.5、1和5 Gy）中，这种作用是可逆的。相反，该作用在10和20 Gy组中持续存在，表明RIN值<4被抑制。5具有很高的死亡率。到第6天时，20 Gy的辐射剂量具有致死性，并需要安乐死。任何时候，低RIN（<2.5）都会导致100％死亡率。合并的放射线灼伤造成的死亡率显着增加，因此没有双重伤害的动物存活到第3天以上，并且没有放射剂量> 1 Gy导致存活到第1天。在存活的双重攻击小鼠中，对RIN的抑制作用较小。在任何时间点，仅烧伤小鼠的RIN值均未发现统计学上的显着变化。在对动物模型的这项研究中，提出了一种简单而准确的评估血液中辐射剂量暴露量（可能预测致死率）的方法的概念证明。