Background: The effects of heat acclimation (HA) on the hypothalamus after exertional heatstroke (EHS) and the specific mechanism have not been fully elucidated, and this study aimed to address these questions. Methods: In the present study, rats were randomly assigned to the control, EHS, HA, or HA + EHS groups (n = 9). Hematoxylin and eosin (H&E) staining was used to examine pathology. Tandem mass tag (TMT)-based proteomic analysis was utilized to explore the impact of HA on the protein expression profile of the hypothalamus after EHS. Bioinformatics analysis was used to predict the functions of the differentially expressed proteins. The differential proteins were validated by western blotting. An enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines in the serum. Results: The H&E staining (n = 5) results revealed that there were less structural changes in hypothalamus in the HA + EHS group compared with the EHS group. Proteomic analysis (n = 4) revealed that proinflammatory proteins such as argininosuccinate synthetase (ASS1), high mobility group protein B2 (HMGB2) and vimentin were evidently downregulated in the HA + EHS group. The levels of interleukin (IL)-1β, IL-1, and IL-8 were decreased in the serum samples (n = 3) from HA + EHS rats. Conclusions: HA may alleviate hypothalamic damage caused by heat attack by inhibiting inflammatory activities, and ASS1, HMGB2 and vimentin could be candidate factors involved in the exact mechanism.

Neuroinflammation after cerebral ischemia is a key event in progressive brain injury after ischemic stroke. The JAK2/STAT3 pathway is pivotal for neuroinflammation; however, its role in brain senescence after ischemic stroke is unclear. Here, we report that inflammation is increased in the brains of C57BL/6 stroke mice. Treatment of ischemic stroke in adult mice with a JAK kinase inhibitor (AG490) alleviated neurobehavioral defects, reduced brain infarct volume, reduced expression of pro-inflammatory cytokines, and decreased activation of pro-inflammatory microglia. Moreover, AG490 treatment reduced oxidative DNA damage and cellular senescence in the brains of mice following ischemic stroke. Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) were associated with inflammation and senescence. Furthermore, AG490 blocked cGAS/STING/NF-κBp65 expression. Overall, our results indicate that inhibition of JAK2/STAT3 can alleviate the negative neurological consequences of ischemic stroke, likely due to repression of cGAS/STING/NF-κB p65, leading to reduced neuroinflammation and neuronal senescence. Therefore, JAK2/STAT3 may represent a viable therapeutic target for preventing senescence after ischemic stroke.

目的 探讨劳力型热射病患者发病早期凝血及纤溶系统功能紊乱与其短期预后之间的关系.方法 回顾性分析劳力型热射病患者的临床资料,根据发病28 d的临床结局将患者分为死亡组及存活组.比较死亡组及存活组的临床特征及凝血、纤溶生物学标志物差异,进行Cox回归分析.对危险因素进行受试者工作特征曲线分析并绘制Kaplan-Meier生存曲线.结果 156例劳力型热射病患者中有28例死亡.与存活组相比,死亡组具有更高的核心体温、更低的收缩压(SBP)(P＜0.05).死亡组及存活组患者的凝血酶原时间国际标准化比例(PT-INR)、活化部分凝血活酶时间(APTT)、D-二聚体(DD)、血小板(PLT)、纤维蛋白原(Fib)、凝血酶原活动度(PTA)水平比较差异有统计学意义(P＜0.001).多因素Cox回归显示PT-INR、APTT、PLT和SBP为影响劳力型热射病患者生存时间的独立影响因素(P＜0.05).PT-INR、APTT、PLT预测劳力型热射病患者28 d死亡的诊断最佳截断值分别为1.70、44.75 s和85.0×109/L.以最佳截断值分组,PT-INR≥1.70 者与 PT-INR＜1.70 者 比较,APTT≥44.75 s 者与 APTT＜44.75 s 者 比较,PLT＜85 × 109/L 者与PLT≥85×109/L者比较,其预估生存时间差异均有统计学意义(P＜0.001).结论 尽管凝血和纤溶功能紊乱均与劳力型热射病严重程度有关,但严重的凝血活化(而不是纤溶亢进)可能最终导致了患者的预后不良.

Background: Exertional heatstroke (EHS) is an emergency with a high mortality rate, characterized by central nervous system dysfunctions. This study aims to establish a Heat acclimation/acclimatization (HA) rat model in locomotion to recapitulate the physical state of human in severe environment of high temperature and humidity, and investigate the mechanism of organism protection in HA. (2) Methods: Wistar rats were exposed to 36 degrees C and ran 2 h/d for 21 days, acquired thermal tolerance test was conducted to assess the thermotolerance and exercise ability. Core temperature and consumption of water and food were observed. Expression of HSP70 and HSP90 of different tissues were determined by WB. Pathological structure of brain tissue was detected with HE staining. Proteomics was used to identify the differently expressed proteins in cerebral cortex of different groups. And key molecules were identified by RT-PCR and WB. (3) Results: HA rats displayed stronger thermotolerance and exercised ability on acquired thermal tolerance test. Brain water content of HA + EHS group reduced compared with EHS group. HE staining revealed slighter brain injuries of HA + EHS group than that of EHS. Proteomics focused on cell death-related pathways and key molecules Aquaporin 4 (AQP4) related to cell edema. Identifi-cation results showed HA increased AQP4, Bcl-xl, ratio of p-Akt/AKT and Bcl-xl/Bax, down-regulated Cleaved Caspase-3. (4) Conclusions: This HA model can ameliorate brain injury of EHS by reducing cerebral edema and cell apoptosis, offering experimental evidence for EHS prophylaxis.

目的 分析血栓弹力图(thromboelastography,TEG)在热射病(heat stroke,HS)患者凝血状态评估中的应用价值,并探讨其对HS患者短期死亡的预测价值.方法 回顾性分析了2015年1月—2019年12月就诊的HS患者.根据其28 d结局将患者分为病死组及存活组.分析病死组及存活组的临床特征差异,应用TEG评估2组间凝血状态差异,探讨TEG对HS患者28 d死亡有预测价值的参数及与死亡有关的危险因素.结果 存活组与病死组在性别、年龄、BMI、基础病、最高核心体温等方面差异无统计学意义(P>0.05).39位HS患者中,TEG显示凝血状态异常者有17例(43.59％).病死组低凝状态(83.33％)比例高于存活组(30.30％)(P=0.046).病死组HS R值延长(P=0.009).与存活组比较,病死组K值偏高,α角及CI偏低,但2组间差异无统计学意义(P>0.05).R值预测HS 28 d死亡的受试者工作特征曲线下面积为0.849(95％CI为0.694～0.992,P=0.007),诊断界值为6.75 min,对应灵敏度、特异度和约登指数分别83.30％、87.50％、0.71.α角和CI的ROC曲线下面积分别是0.227和0.221,对死亡无预测价值.多因素Logistic回归分析发现低凝状态R值、α角和CI均不是HS患者28 d死亡的独立危险因素(P>0.05).结论 HS患者常合并凝血功能异常.重症者多表现为低凝状态.TEG检测可以反映HS严重程度,对短期死亡有一定的预测价值.

BACKGROUNDExertional heat stroke (EHS) is a life-threatening illness that can lead to multiple organ damage in the early stage.OBJECTIVEThis study aimed to investigate the relationship between 24-hour indicators and mortality in patients with EHS.METHODSThe records of EHS patients hospitalized were collected and divided into the death group and the survival group. We then analyzed the demographic characteristics and APACHE II scores and laboratory results of the participants in the blood within the first 24 h after hospitalization, and assessed whether these candidate indicators differed between the death group and the survival group. Cox regression analysis of the survival data was performed to explore the relationship between early indicators and prognosis.RESULTSThe levels of plasma PT, APTT, TT, and INR were significantly higher in the death group than in the survival group. The blood PLT count and the levels of PTA and Fb were significantly lower in the death group than in the survival group, while the levels of BU, SCr, ALT, AST, TBil, and DBil were significantly higher in the death group than in the survival group. Furthermore, the levels of Mb, LDH, TNI, and NT-proBNP were significantly higher in the death group than in the survival group, while there was no significant difference in CK levels between the two groups.CONCLUSIONPatients with EHS often had multiple organ injuries in the early stage (within 24 h), while those cases in the death group were more severe.

Exertional rhabdomyolysis (ER) often occurs during prolonged intense exercise in hot environments, posing a threat to the health of military personnel. In this study we aimed to investigate possible risk factors for ER and provide further empirical data for prevention and clinical treatment strategies.

Objective: The purpose of this study is to evaluate the factors involved in the early stage of exertional heat stroke (EHS) that are associated with mortality. Methods: In this retrospective, case-control study, patients from 11 tertiary medical centers in China were enrolled from January 1, 2012, to December 31, 2019. Demographic information, underlying diseases, ambient temperature, and relative humidity, clinical manifestations, initial body temperature, time from onset to diagnosis of EHS (including suspected), and the duration of body temperature > 38 degrees C of all enrolled patients were recorded. The occurrence of organ dysfunction within 72 h was evaluated, and in-hospital deaths were recorded. The patients were subsequently divided into a survival group and a non-survival group. The "case" refers to patients in the non-survival group, while the "control" refers to patients without death. Results: Of the 214 hospitalized patients with EHS, 183 survived and 31 died, and the overall mortality was 14.49% (31/214). A binary logistic regression showed that only the duration of body temperature > 38 degrees C (OR 1.80, 95% CI 1.34-2.42) and the number of organs damaged within 72 h of onset (OR 6.54, 95% CI 2.31-18.56) were statistically significant in terms of risk of death in hospital (p < 0.05). A goodness of fit test produced a p-value of 0.76. According to receiver operating characteristic curve (ROC) analysis, the areas under the curve (AUC) were 0.989 (95% CI 0.978-1.000; p < 0.05) and 0.936 (95% CI 0.896-0.976; p < 0.05). Conclusion: Of the various factors involved in the early stage of the disease, the duration of high body temperature and the number of organs damaged within 72 h of onset were independent risk factors and predictors associated with death.

Objective: To evaluate the prognostic value of routine coagulation tests for patients with heat stroke. Methods: This was a multi-center retrospective study. Patients who arrived at the hospital <24 h after the onset of Heat Stroke (HS) were included. The routine coagulation variables were detected within 24 h after the onset, including the lowest platelet count (PLC). Results: 60-day mortality rate was 20.9%. The median Prothrombin Time-International Normalized Ratio (PTINR) of the non-surviving patients was significantly higher than that of the survivors (P < 0.01). The median Activated Partial Thromboplastin Time (APTT) in non-surviving patients was significantly higher than in the surviving patients (P < 0.01). A Cox regression analysis revealed that 60-day mortality was associated with PT-INR (P = 0.032) and APTT (P = 0.004). The optimal PT-INR point for predicting 60-day mortality rate was 1.7. The optimal APTT point for predicting 60-day mortality was 51.45. Patients with increased PT-INR (>_1.7) levels had, overall, a significantly reduced survival time (P < 0.01). Patients with elevated APTT (>_51.45) also had a decrease in survival time (P < 0.01). The prognostic scoring, with increased PT-INR (>_1.7) and prolonged APTT (>_51.45) at one point each, was also demonstrated to be useful in predicting 60-day mortality. Patients whose temperature fell to 38.9 degrees C within 30 min had significantly lower levels of PT-INR and APTT within 24 h than those who took longer to cool down. Conclusions: A prolonged APTT and elevated PT-INR within 24 h are independent prognostic factors of 60-day mortality in HS. (c) 2020 Elsevier Inc. All rights reserved.

背景 劳力型热射病(exertional heat stroke,EHS)是一种主要因运动或劳作产生过量的内源性热而引起的重度中暑,目前尚无成熟的EHS实验动物模型建模方法和标准.目的 通过植入式生物遥测技术的应用,建立稳定可靠的EHS大鼠模型,阐明高温和运动下EHS大鼠的核心温度(core temperature,Tc)、血压(blood pressure,BP)、心率(heart rate,HR)等基本生理参数的变化规律.方法 取体质量250～300 g健康成年雄性Wistar大鼠18只,通过手术将可实时遥测Tc、BP、HR的无线植入子植入大鼠腹腔,恢复1周后进行适应性跑步训练.训练1周后大鼠进入高温、高湿环境模拟舱,实验舱的环境温度设置为(39.5±0.3)℃,相对湿度为55％ ±5％;大鼠以阶梯式增速方案进行跑步,疲劳后停止,出现重度意识障碍表现后结束热暴露出舱,出舱后自然降温.实验中持续监测大鼠Tc、BP、HR等参数变化,记录生存时间.死亡EHS大鼠即刻解剖,观察病理学变化.结果 在18只进行植入子手术的大鼠中,7只大鼠术后恢复良好,手术总体成功率为38.9％.遥测模型完整记录了热应激下大鼠的Tc、BP、HR等生理参数变化过程,随着Tc的迅速上升,BP、HR同步到达峰值并于出舱前急剧下降.病理学检查验证了EHS大鼠的多器官损伤.结论 植入式生物遥测技术可以实时监测EHS大鼠实验模型的生理参数,有助于进一步挖掘EHS的病理生理学变化特点和机制,为后续EHS研究提供了必要工具.

Abstract BackgroundExertional rhabdomyolysis (ER) often occurs during prolonged intense exercise in hot environments, posing a threat to the health and safety of military personnel.ObjectiveTo investigate possible risk factors of ER and provide further empirical data for prevention and clinical treatment strategies for ER.MethodsIn this study, a systematic retrospective investigation on 116 concurrent cases of ER was conducted. Demographic, clinical, and exercise-related data were collected from both ER cases and controls which were allotted by 1:3 proportion. Conditional logistic regression analyses were performed to calculate the significance of the association between each potential risk (or protective) factors and ER.ResultsThe adjusted ER prediction model finally included the following variables that significantly increased (or decreased) the risk of acquiring ER: age (odds ratios [OR] 0.59, 95% confidence interval [CI]0.45–0.79), body mass index (BMI, OR 1.11, 95%CI 1.01–1.24), dark-colored urine after training (OR 2.98, 95%CI 1.58–5.64), frequent fruit consumption (OR 0.54, 95%CI 0.29–0.98), active hydrating habit (OR 0.31, 95%CI 1.58–5.64), water replenishment ≥ 2L on the training day (OR 0.18, 95%CI 0.06–0.54), water replenishment ≥ 500 ml within 1 hour before training (OR 0.32, 95%CI 0.11–0.90), lack of physical exercise in the last half-year (OR 3.23, 95%CI 1.34–7.80).ConclusionsIn military training, emphasis should be placed on incremental adaptation training prior to more intense training, and close attention should be paid to overweight and previously sedentary recruits. Fluid replenishment before exercise, increased fruit intake, and proper potassium supplementation may help to prevent ER.

人体暴露在高温(高湿)环境和(或)剧烈运动一定时间后,如果吸热-产热-散热构成的热平衡被破坏,机体局部或全身热蓄积超过体温调节的代偿限度时会出现一系列病理生理变化,表现为由轻及重的连续过程,统称为中暑(heat illness)[1].根据中暑的最新分级建议[2] ,分为轻度中暑(先兆中暑)、中度中暑(热衰竭)和重度中暑(热射病).