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Objective:To investigate the value of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of patients with severe heat stroke.Methods:A retrospective analysis was performed on patients with severe heat stroke hospitalized in the ICU of Changzhou No. 2 People's Hospital from June 2013 to September 2019. The patients were divided into the survival group and death group according to their 30-day survival. The basic data of the patients were recorded. Blood routine, liver and kidney function parameters, troponin, brain natriuretic peptide, myocardial enzyme spectrum, blood coagulation routine, and acute physiology and chronic health evaluation (APACHE)Ⅱ were analyzed within 24 h after admission. Multivariate COX regression analysis was used to screen the risk factors of 30-day death. Spearman correlation test was used to analyze the correlation between NLR and APACHEII score. Receiver operating characteristic (ROC) curves were drawn to assess the predictive value of NLR for the 30-day death in patients with severe heat stroke. Kaplan-Meier survival curve was used to analyze 30-day cumulative survival of high-risk patients.Results:A total of 115 patients with severe heat stroke were included in this study, and they were divided into the survival group ( n=92) and the death group ( n=23) according to the prognosis. NLR in the death group was significantly higher than that in the survival group ( P<0.05). Multivariate COX regression analysis showed that NLR was an independent risk factor for death after adjusting confounders ( HR=1.091, 95% CI: 1.049-1.136, P<0.001). Spearman correlation test showed a correlation between NLR and APACHEII score ( r=0.655, P<0.001). ROC curve analysis showed that NLR had the greatest predictive value for 30-day death, with an area under ROC curve (AUC) of 0.787, a sensitivity of 82.6%, a specificity of 67.4%, and the cut-off value of 7.35. Kaplan-Meier survival analysis curve shows that patients in the below NLR cut-off value group had a significantly higher 30-day survival rate than those in the above NLR cut-off value group ( P<0.001). Conclusions:The increased NLR is a high risk factor for death in patients with severe heat stroke, and helps predict the prognosis of patients with severe heat stroke.
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Heat stroke can be divided into two types: exertional and classic, mainly manifested as a clear history of exposure to hot temperature/high heat environment or intense physical activity in hot environment, core temperature exceeding 40 ℃, accompanied by central nervous system changes (altered consciousness, epilepsy, psychiatric symptoms, etc.) and multiple organ damage, including respiratory failure, impaired liver and kidney function, rhabdomyolysis, coagulation disorders, abdominal distension, and diarrhea. Its pathology may be manifested as organ endothelial cell damage, inflammatory response, extensive thrombosis, and bleeding tendency. The main treatment measures are cooling therapy, and when combined with other organ damage, organ support or replacement therapy should be carried out in time, including blood transfusion to improve coagulation function and blood purification therapy. Hyperbaric oxygen therapy may improve the prognosis of patients with ischemic hypoxic encephalopathy. We reported a case of a firefighter with sudden impaired consciousness and high fever during forest fire fighting. The patient was sent to a local hospital and his head computed tomography (CT) results showed unclear cerebral gyrus, suggesting severe cerebral edema, and finally diagnosed as heat stroke. After being transferred to Liuzhou Workers' Hospital, his condition continued to deteriorate and signs of multiple organ failure appeared. The patient's cerebral edema was reversed and further development of heat stroke was prevented through early cooling, sedation and anti-epilepsy, endotracheal intubation ventilator-assisted breathing, anti-infection, fluid resuscitation, infusion of fresh frozen plasma and platelets to improve coagulation function, immunomodulatory therapy, renal replacement therapy, and timely artificial liver therapy. Hyperbaric oxygen therapy was ordered during the rehabilitation phase, and the patient recovered well at discharge, leaving no obvious neurological sequelae. Its prognosis is much better than that predicted at admission.
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Objective To analyze the epidemiological characteristics of occupational diseases caused by physical factors in Guangdong Province from 2013 to 2022, and to evaluate the key risk points of its incidence. Methods The data of newly diagnosed and suspected occupational diseases caused by physical factors in Guangdong Province from 2013 to 2022 were collected from the Occupational Diseases and Hazards Monitoring Information System under China Disease Prevention and Control Information System, and were analyzed retrospectively. The key risk points of occupational diseases caused by physical factors were evaluated. Results A total of 661 cases of occupational diseases caused by physical factors were reported in Guangdong Province from 2013 to 2022, showing an overall increasing trend, with an average annual growth rate of 29.6%. The major occupational diseases caused by physical factors were occupational hand-arm vibration disease and occupational heat stroke, accounting for 59.5% and 39.6%, respectively. The nine prefecture-level cities of Pearl River Delta region accounted for 98.5% of the new cases. The cases were distributed mainly in the manufacturing industry (77.0% of the cases). A total of 294 enterprises were involved in the analysis of newly diagnosed occupational diseases caused by physical factors. Occupational hand-arm vibration cases appeared to be significantly aggregated in specific enterprises, and other disease cases were mostly sporadic. The types of enterprise registration were mainly Hong Kong-, Macao-, and Taiwan-invested enterprises and domestic-funded enterprises, accounting for 53.1% and 41.4%, respectively. In terms of enterprise size, large-scale and small-scale enterprises accounted for 56.5% and 21.4% of cases, respectively. A total of 27.4% of workers with occupational diseases caused by physical factors were identified as suspected occupational diseases before be diagnosed as occupational diseases, all of which were hand vibration disease and heat stroke In the future, attention should be paid to the risks of mass events of occupational hand-arm vibration disease, outbreaks of occupational heat stroke, and missed diagnosis of suspected occupational hand-arm vibration disease. Conclusion Among all occupational diseases caused by physical factors in Guangdong Province, attention should be paid on occupational hand-arm vibration disease and occupational heat stroke. Occupational hand-arm vibration disease has a high risk of group morbidity. Construction workers and sanitation workers have a high potential risk of occupational heat stroke.
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Introducción: El golpe de calor es una enfermedad que fue descrita hace más de 2000 años, sin embargo, los cambios climáticos que se han presentado en las últimas décadas han permitido que su prevalencia esté en aumento. Se considera una entidad compleja en la cual existe un compromiso importante de la termorregulación corporal y, en consecuencia, del resto de sistemas. Objetivos: Orientar al abordaje adecuado y óptimo de conceptos clínicos, epidemiológicos, factores el riesgo, presentación clínica y repercusión sobre los diferentes sistemas. Métodos: Se realizó una revisión de la literatura científica de personas con golpe de calor, en quienes se evaluaron sus factores asociados, métodos diagnósticos y manejos terapéuticos. Se realizó una búsqueda de la literatura en las siguientes bases de datos: Pubmed/Medline, Science Direct, Scopus, DOAJ, Embase, Cochrane, Direme, Redalyc y SciELO. Conclusiones: El golpe de calor es una urgencia médica que implica un manejo rápido y óptimo dado su morbilidad y mortalidad, lo cual puede minimizarse si se cumplen los objetivos de tratamiento. El enfriamiento por inmersión en agua helada, por convección o evaporación son las medias más usadas. Evitar la falla multiorgánica es el segundo objetivo terapéutico(AU)
Introduction: Heat stroke is a disease described more than 2000 years ago; however, the climatic changes that have occurred in recent decades have allowed an increase in its prevalence. It is considered a complex entity in which there is an important compromise of body thermoregulation and, consequently, of the rest of the systems. Objectives: To define important concepts concerning heat stroke, risk factors, clinical presentation and repercussions on the different systems, as well as to guide an appropriate and optimal management. Methods: A review of the scientific literature about people with heat stroke was carried out to assess its associated factors, diagnostic methods and therapeutic management. A literature search was performed in the following databases: Pubmed/Medline, Science Direct, Scopus, DOAJ, Embase, Cochrane, Bireme, Redalyc, and SciELO. Conclusions: Heat stroke is a medical emergency that requires rapid and optimal management given its morbidity and mortality, which can be minimized if management goals are met. Cooling by immersion into ice water, convection or evaporation are the most commonly used measures. Avoidance of multiorgan failure is the second therapeutic objective(AU)
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Humans , Male , Female , Heat Stroke/diagnosis , Heat Stroke/physiopathology , ColombiaABSTRACT
Both the frequency and severity of heat stress-related health problems have been increasing globally, probably due to global warming. The Intergovernmental Panel on Climate Change published a landmark climate report, the 6th Assessment Report, which shocked the world. It emphasized that anthropogenic activities, such as the combustion of fossil fuels, oil, gas, and coal, were responsible for climate change. The combination of population aging, and increased temperatures has meant that the number of people requiring emergency transport for heatstroke has been increasing in Japan from 2008 to 2020. The increase in ambient temperatures and the number of patients requiring emergency transport were strongly correlated (Spearman correlation coefficient: r=0.669 and P=0.008). Like many human activities, medical care is resource intensive and contributes significantly to climate change through the consumption of energy and water, as well as the emission of greenhouse gases. As healthcare professionals, we need to be cognizant of how our eco-friendly activities both on and off the job can contribute to saving both the patients and us.
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Heat stroke is a critical and health-threatening disease, triggered by thermal stimulus and progressing rapidly. It can give rise to multiple organ dysfunction syndrome (MODS), resulting in a high mortality rate. Nearly 30% of survivors will suffer with different sequelae, for instance, the neurological sequelae. Currently, the early rapid cooling is the focus of therapy for heat stroke. Therefore, it is imperative to design a cooling module suitable for the treatment of heat stroke in the field and in the hospital to realize the goal of early rapid cooling and the effective targeted temperature management (TTM). The cooling device is composed of a cooling blanket and a cooling cap. The blanket and cap are made by temperature changeable fabric. The cooling blanket comprises a backing layer, a buffer layer, a flexible heat conduction capsule body, a temperature changing component, a fixed part and a temperature sensor. The cooling cap includes a main body and two side ears, in which the main body is worn on the top of the patient's head, and the front is equipped with a flexible display screen, which is convenient for real-time monitoring the temperature of the temperature change component of the cooling blanket. The lateral ear can wrap the patient's ears and neck, and the tympanic membrane thermometer is designed to monitor the tympanic membrane temperature in real time. The tympanic membrane thermometer is also designed at the ear to monitor the tympanic auditory canal temperatures in real time.Continuous dynamic temperature monitoring can guide the duration of cooling treatment and stop cooling in time. The cooling component is portable, easy to operate, real-time temperature monitoring, excellent cooling effect and reusable. It is used for on-site first aid, transportation and continuous cooling for patients with heat stroke in the ward.
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@#BACKGROUND: This study aimed to establish an effective nomogram to predict the survival of heat stroke (HS) based on risk factors. METHODS: This was a retrospective, observational multicenter cohort study. We analyzed patients diagnosed with HS, who were treated between May 1 and September 30, 2018 at 15 tertiary hospitals from 11 cities in Northern China. RESULTS: Among the 175 patients, 32 patients (18.29%) died before hospital discharge. After the univariate analysis, mechanical ventilation, initial mean arterial pressure <70 mmHg, maximum heart rate, lab results on day 1 (white blood cell count, alanine aminotransferase, creatinine), and Glasgow admission prediction score were included in multivariate analysis. Multivariate Cox regression showed that invasive ventilation, initial mean arterial pressure <70 mmHg (1 mmHg=0.133 kPa), and Glasgow admission prediction score were independent risk factors for HS. The nomogram was established for predicting 7-d and 14-d survival in the training cohort. The nomogram exhibited a concordance index (C-index) of 0.880 (95% confidence interval [95% CI] 0.831-0.930) by bootstrapping validation (B=1,000). Furthermore, the nomogram performed better when predicting 14-d survival, compared to 7-d survival. The prognostic index cut-off value was set at 2.085, according to the operating characteristic curve for overall survival prediction. The model showed good calibration ability in the internal and external validation datasets. CONCLUSION: A novel nomogram, integrated with prognostic factors, was proposed; it was highly predictive of the survival in HS patients.
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The thermal environment increases the risk of thermal injury for persons under high temperature environment. A full understanding of the effects and hazards of the thermal environment on the human body is of great significance to improve the awareness of persons under high temperature environment and reduce occupational heat damage during work. The authors mainly review the thermal environment from aspects of the definition, mechanism of its influence on main functional systems of the human body, influencing factors of heat stress and progress of protection, so as to provide references for the identification and protection of heat-induced diseases for workers under high temperature environment.
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In the trend of global warming and the increasing number of participating in high-intensity sports, the incidence of heat stroke is increasing year by year. Heat stroke is categorized to the class of heat emergent diseases. If there is no quick and effective treatment, the mortality rate is as high as 50%. Early, rapid, and effective cooling is the key point in the treatment of heat stroke. The early recognition and rapid lowering the core body temperature to 38.9 ℃ within 30 minutes of exertional heat stroke results in better clinical outcome with the fewest complications, however, the "golden 30 minutes" is far from enough to complete emergency transport and evaluation. Therefore, it is urgent to develop a first aid suit for heat stroke suitable for field treatment and transportation, so as to achieve the treatment goal of early rapid and effective cooling in field environment. For this purpose, the medical staff of the department of critical care medicine of the Eighth Medical Center of the Chinese People's Liberation Army General Hospital designed and developed the split first aid suit, which is suitable for heat stroke patient in the harsh environment lacking medical supplies and water during transportation. The medical staff who designed the first aid suit obtained a National Utility Model Patent of China (ZL 2020 2 1627326.4). The split heat stroke first aid suit is composed of four main parts: a sleeveless coat, a hat, sleeves and wrapped pants. All of them are made by temperature changeable fabric which is a composite material made by fine porous silica gel particles and potassium nitrate. The cuffs of the sleeveless top of the clothes part and the sleeves are connected as a whole by the connecting pieces; and the front end of the hem of the clothes part and the wrapped trousers are also connected as a whole by the connecting pieces, which is convenient for fixing and transportation. In order to control the water injection quantity, the water injection bag and the corresponding components are designed to ensure the same amount of water can be injected to the heat stroke first aid suit at each time, so the same frigorific effect can be attainable. The service temperature is 14-18 ℃, so it will not cause local frostbite to patients when used for a long time. This split-type first aid suit can be used in the movement, rescue and transportation of heat stroke patients. It is easy to carry and use with accurate cooling effect with low cost, moreover, it is reusable and can be widely used for on-site emergency and transportation of heat stroke patients.
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Objective:To evaluate the intestinal function in rats with exertional heat stroke (EHS) and explore the protective role of Ruifuping pectin (RFP) against heat related intestinal mucosal injury.Methods:One hundred and twenty healthy special pathogen free (SPF) male Sprague-Dawley (SD) rats were randomly divided into normothermic control group, EHS model group, hyperthermic plus drinking water group (H 2O+EHS group) and hyperthermic plus pectin group (RFP+EHS group) with 30 rats in each group. The rats in the H 2O+EHS group and RFP+EHS group were given water 20 mL/kg or RFP 20 mL/kg orally for 5 days during adaptive training period. After 1 week, the temperature control range was adjusted to (37±1)℃ using the temperature control treadmill, and the rat model of EHS was reproduced by one-time high temperature exhaustive exercise. No rehydration intervention was given during the training adaptation period in the EHS model group. The rats in the normothermic control group were maintained to room temperature (25±2)℃ and humidity (55±5)% without other treatment. Behavior tests including withdraw response, righting, and muscle strength were performed immediately after onset of EHS. Blood of inferior vena cava was collected, and the serum inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β, IL-10)] and activity of diamine oxidase (DAO) were detected by enzyme linked immunosorbent assay (ELISA). The intestinal mucosa was collected, after hematoxylin-eosin (HE) staining, and Chiu score was performed to assess EHS induced pathological changes under light microscope. Results:The rats in the EHS model group had behavioral, inflammatory and pathological changes, such as delayed withdraw response and righting, decreased forelimb pulling, increased inflammatory index, and obvious intestinal mucosal injury, which indicated that the reproduction of the EHS model was successful. There was no significant difference in above parameters between the H 2O+EHS group and the EHS model group except that the inflammatory index in the RFP+EHS group was improved. Compared with the EHS model group, the withdraw reflex to pain and righting after RFP pretreatment in the RFP+EHS group were significantly improved (righting score: 1.4±0.2 vs. 0.3±0.2, withdraw reflex to pain score: 1.0±0.1 vs. 0.2±0.1, both P < 0.05), the muscle strength was significantly increased (N: 13.0±0.5 vs. 8.2±0.6, P < 0.01). The levels of pro-inflammatory factors in the RFP+EHS group were significantly lower than those in the EHS model group [TNF-α (ng/L): 67.5±9.2 vs. 194.3±13.7, IL-6 (ng/L): 360.0±54.1 vs. 981.2±84.4, IL-1β (ng/L): 33.7±9.0 vs. 88.7±6.1, all P < 0.01], while the level of anti-inflammatory factor IL-10 was higher than that in the EHS model group (ng/L: 208.7±10.5 vs. 103.7±7.0, P < 0.01). The degree of intestinal mucosal injury in the RFP+EHS group was less severe than that in the EHS model group, and the Chiu score and DAO were significantly lower than those in the EHS model group [Chiu score: 1.5±0.2 vs. 3.8±0.0, DAO (U/L): 83.7±6.7 vs. 128.7±10.5, both P < 0.05]. Conclusions:High temperature training can damage the intestinal barrier function, and induce endotoxemia and systemic inflammatory response syndrome (SIRS) in rats. Oral prophylactic RFP can protect the intestinal barrier function, alleviate SIRS, and promote the recovery of basic nerve reflex and muscle strength after the occurrence of EHS in rats.
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Objective:To observe whether endoplasmic reticulum stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation were involved in severe heat stroke induced intestinal mucosal injury and to investigate the potential protective effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA).Methods:Thirty male BALB/c mice were randomly (random number) assigned to 3 groups: the control group, heat stroke group (HS), and 4-PBA pretreatment group (4-PBA+HS, 4-PBA 120 mg/kg, intraperitoneal injection). Mice in the control group were placed at room temperature, while mice in the HS group and 4-PBA+HS group were placed in a prewarmed chamber [temperature (35.5±0.5) °C, humidity (60.0±5.0)%]. A rectal temperature (Tc) that reached 42 °C was considered to indicate severe heat stroke. The concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) in intestinal homogenate were analyzed by a colorimetric method, serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) were assessed by ELISA, intestinal histopathology was evaluated by hematoxylin and eosin (HE) staining, intestinal ultrastructure was observed by electron microscopy, and the protein expression of GRP78, CHOP, NLRP3 and cleaved caspase-1 were analyzed by Western blot. Data were statistically analyzed by ANOVA test and LSD- t multiple comparison test if homogeneous variance, or analyzed by Welch test and Dunnett's T3 multiple comparison test if heterogeneous variance. Results:The concentration of MDA in the HS group was increased ( t=14.243, P<0.01), while SOD was decreased compared with that in the control group ( t=7.781, P<0.01), and the concentrations of serum IL-1β and IL-18 were significantly elevated ( t=12.664, P<0.01; t=16.240, P<0.01). Under light microscopy, extensive destruction of small intestinal villi and inflammatory cell infiltration were observed in the intestines of mice with severe heat stroke. Transmission electron microscopy showed that endoplasmic reticulum structures were significantly expanded, and mitochondria were vacuolated in the intestines of mice with severe heat stroke. Compared with those in the control group, the protein expression levels of GRP78, CHOP, NLRP3 and cleaved caspase-1 in the small intestine were elevated in the HS group ( t=14.824, P <0.01; t=12.667, P<0.01; t=9.298, P<0.01; and t=6.588, P=0.001). Compared with those in the HS group, mice in the 4-PBA pretreatment group exhibited reduced concentrations of MDA ( t=9.167, P<0.01), increased SOD ( t=6.077, P<0.01) , and reduced serum IL-1β and IL-18 levels ( t=4.889, P= 0.001; t=5.693, P<0.01). In addition, 4-PBA pretreatment significantly alleviated the pathological disruption and ultrastructural damage to small intestine tissues. Moreover, 4-PBA pretreatment reduced GRP78, CHOP , NLRP3 and cleaved caspase-1 protein expression ( t=9.080, P<0.01; t=7.152, P<0.01; t=4.249, P=0.005; t=3.650, P=0.011). Conclusions:Endoplasmic reticulum stress and NLRP3 inflammasome are involved in intestinal mucosal injury induced by severe heat stroke. 4-PBA plays a protective role by alleviating endoplasmic reticulum stress and NLRP3 inflammasome activation.
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Objective:To explore the molecules mechanism of Pin1 in severe heat stroke induced acute lung injury by observing Pin1 regulate oxidative stress and apoptosis formation in pulmonary microvascular endothelial cells (PMVECs) and lung tissue in heat stressed mice.Methods:In vitro, a PMVECs heat stress (HS) model was established. In the control group, PMVECs were placed in a standard 37 °C, 5% CO 2 cell incubator; in the HS group, PMVECs were placed in a 43 °C cell incubator for 2 h, then the cells were further incubated at 37 °C for 1, 3, 6 or 12 h. PMVECs were pretreated with Pin1 inhibitor Juglone (1 μmol/L) 1 h before 43 °C of HS. In vivo, a severe heat stroke mouse model was established. In the HS group, the mice were kept at the simulation of climate chamber with temperature (35.5±0.5) °C, humidity (60±5)%, the rectum temperature in mice was measured by the anal rectal temperature table, when the temperature reached 42 °C, the heat exposure was stopped, and the mice were sacrificed at 1, 3, 6 or 12 h after HS. In the control group, the mice were kept at room temperature (25±0.5) °C. Mice received daily intraperitoneal administration of Pin1 inhibitor Juglone (1 mg/kg) for 3 d before HS. The protein level of Pin1, cleaved caspase-9 and cleaved caspase-3 were analyzed by Western blot, the level of O 2-˙ in cells was observed by DHE staining and fluorescence microscopy, the levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in lung tissue were measured by ELISA, the pathological changes of mice in different group were detected by HE staining, and the expression of Pin1 in the lung tissue of different groups was detected by immunohistochemical staining, the apoptosis rate of the lung tissue in different groups was tested by TUNEL staining. Results:At 1 h after HS, the protein expression of Pin1 in PMVECs and lung tissue began to increase in a rewarming time-dependent manner ( F=771.6, P<0.05; F=1 035, P<0.05). Cleaved caspase-9 protein in PMVECs and lung tissue started to increase at 3 h post-HS, then increased with a rewarming time-dependent manner ( F=729.8, P<0.05; F=1 773, P<0.05). The protein expression of cleaved caspase-3 in PMVECs and lung tissue also started to increase at 3 h after HS and the expression continued to be increased with prolonged rewarming time, and the trend was consistent with cleaved caspase-9 ( F=1 084, P<0.05; F=1 252, P<0.05). In addition, HS induced the increased release of O 2-˙ from PMVECs, HS induced the imbalance of oxidation-antioxidant system in lung tissue of mice after HS which verified by the continuous release of MDA ( F=114.2, P<0.05) and the continuous inhibition of SOD activity ( F=99.15, P<0.05). Compared with the HS group, pretreatment with Pin1 inhibitor Juglone in PMVECs and mice before HS significantly inhibited the protein expression of Pin1, cleaved caspase-9 and cleaved caspase-3 (all P<0.05), pretreatment with Pin1 inhibitor greatly reduced the release of O 2-˙ in PMVECs after HS, and promoted the restore of the oxidation-antioxidant system balance of lung tissue in mice with severe heat stroke. In addition, compared with the HS group, inhibiting the expression of Pin1 significantly decreased HS induced MDA release [(11.53±0.84) nmol/mL vs (9.65±0.69) nmol/mL, t=12.52, P<0.05], promoted the restore of SOD activity [(41.18±3.45) U/mL vs (57.52±4.83) U/mL, t=5.57, P<0.05] and improved the pathological damage of lung tissue as well as decreased the occurrence of apoptosis in post-HS mice. Conclusion:It was confirmed that Pin1 is involved in heat stress induced acute lung injury mainly through mediating oxidative stress response and apoptosis.
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Objective:To investigate the epidemiological characteristics of heat stroke cases in Minhang District of Shanghai in 2013-2018 and to explore potential risk factors， so as to provide the evidence for making the preventive and control measures. Methods:Meteorological parameters and heat stroke cases during May-September were included for statistical analysis. Results:A total of 101 heat stroke cases were studied， in which the majority occurred during June-August. Male cases were more than female cases and 51.5% （52/101） of the cases were severe cases. The incidence of severe heat stroke in people aged 40-59， and 60 and over was significantly higher than that in people under 40 years old. The number of people with severe heat stroke was positively correlated with daily maximum temperature and daily minimum temperature， whereas the number of mild heat stroke was only positively correlated with daily maximum temperature. More than half of total cases （86 cases） were documented in 15 heat wave periods， two of which had significantly increased risk. Conclusion:High temperature in summer is dangerous in Minhang District of Shanghai. Men and older people are susceptible to heat stroke， which occurs mainly in the period of high temperature in July and August. The period of daily highest temperature ≥35 ℃， especially during continual high temperature， is the key stage for heat stroke prevention. In addition to focusing on the effect of daily maximum temperature on heat stroke， the effect of daily minimum temperature on severe heat stroke should be considered.
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OBJECTIVE: To predict the material basis of the “cooling blood” effect of Arnebia euchroma, and discusses its potential pathway and mechanism via network pharmacology. METHODS: The chemical constituents of Arnebia euchroma were collected based on database and literature search, the potential active components were filtered by admet SAR method, the targets of potential active ingredients were predicted by bSDTNBI method, the heat stroke related targets was retrieved from OMIM database. The STRING database was used to construct a "predicted target-disease target" protein interaction network, analyze and filter the key targets. A heat stroke model by heat stress-induced in mice to verify the efficacy of the key active ingredient (shikonin) for heat stroke protection was established. RESULTS: A total of 165 chemical constituents of Arnebia euchroma were filtered and 26 potential active ingredients were filtered out to act on 93 targets. Network analysis confirmed that naphthoquinone compounds were the main material basis of its "cooling blood" effect. Arnebia euchroma and heat stroke share multiple targets in the "predicted target-disease target" protein interaction network, suggesting that Arnebia euchroma may have protective effects on against heat stroke(HS). Forty-six key targets were mainly involved in biological processes and pathways such as inflammation, neurotransmitter conduction, redox and coagulation. Pharmacodynamic studies showed that shikonin could significantly prolong the survival time of mice with HS, reduce acute reactions and improve tissue organ damage. CONCLUSION: In summary, Arnebia euchroma may inhibit the inflammatory responses, promote blood circulation, protect the central nervous system, thereby improving multiple organ damage, and play a protective role in against HS.
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Objective To explore the function of losartan on heat-stress induced high-mobility group protein B1 (HMGB1) mediated inflammatory damage in the hepatocytes. Methods Rats were randomized into three groups: sham group (without heat stress), heatstroke group (heatstroke induction followed by i.p. injection of normal saline) and heatstroke+losartan group (heatstroke induction followed by i.p. injection of 50 mg/kg losartan). The serum and liver tissue were harvested nine hours after heatstroke to invest the serum alanine aminotransferase (ALT) levels, liver myeloperoxidase (MPO) levels, liver pathological morphology, serum HMGB1 levels as well as the expression of interleukin(IL)-1β and IL-18 in the liver. In vitro, the HBL3A hepatocyte cell lines were divided into the sham group (without heat stress), heat stress group and heat stress +losartan group (10 μmol/L losartan added into the supernatant after heat stress). Nine hours after heat stress, the cell viability and the levels of supernatant lactate dehydrogenase, supernatant HMGB, cytoplasm and total HMGB1 were all examined. Besides, the level of activated caspase-1 in hepatocytes, supernatant IL-1β and IL-18, as well as the cellular level of reactive oxygen species (ROS), were detected. The effects of recombinant HMGB1 with concentration gradients and 0.2 mmol/L hydrogen peroxide on the levels of IL-1β, IL-18 and HMGB1 in the heat stress hepatocytes treated by losartan were observed. Results In vivo, liver damage occurred in the rats of the heatstroke group. Compared with the heatstroke group, the levels of serum ALT, liver MPO, serum HMGB1, liver tissue IL-1β and IL-18 decreased in the heatstroke+losartan group (P<0.05). In vitro, hepatocytes in the heat stress group were apparently damaged. Compared with the heat stress, the levels of cytoplasmic HMGB1, supernatant HMGB1, IL-1β and IL-18 decreased in the heat stress+losartan group, and the cell survival rate increased (P<0.05). In addition, the HMGB1 inhibitor also reduced the levels of IL-1β and IL-18 in heat stress group hepatocytes. And the supplementation with HMGB1 increased the levels of IL-1β and IL-18 in heat stress hepatocytes treated by losartan (P<0.05). Losartan reduced the level of reactive oxygen species in heat stress hepatocytes, and the supplementation with hydrogen peroxide increased the level of HMGB1 in heat stress hepatocytes treated by losartan (P<0.05). Conclusion Losartan decreased the heat-stress induced HMGB1 mediated inflammatory damage in the hepatocytes.
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Objective To explore the biological function of exosomes secrected by heat-stroke hepatocytes and its effect on liver injury. Methods Exosomes were isolated from donor HepG2 hepatocytes and control hepatocytes by ultra-high-speed centrifugation. The morphology of exosomes was observed by transmission electron microscopy, the diameter of distribution was detected by nano-tracking technology and the expression of characteristic surface markers CD9, CD63 and CD81 were examined by Western blotting. The isobaric tags for relative and absolute quantification methods were applied to analyze the difference in protein composition between the control and HS hepatocyte derived exosomes. Biological information analysis on the differential protein set was performed by the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Recipient hepatocytes were stimulated with sterilized PBS, control hepatocyte exosomes or HS exosomes (10 μg for 24 h), or directly exposed to HS or pretreated with exosome production inhibitor GW4869 2 h before HS. Supernatant alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/lactic dehydrogenase (LDH) levels tested for evaluation of the hepatocyte damage. C57/BL6 mice were injected with sterilized PBS, control hepatocyte exosomes or HS exosomes (40 μg/per mice) through the tail vein, or treated with HS or intraperitoneally injected with GW4869 2 h before HS and sacrificed 9 h thereafter. Plasma ALT/AST/LDH level was examined to assess liver tissue damage. Results The microparticles secreted by hepatocytes are round or elliptical structures with a double-layer membrane coating, with a diameter ranging from 90–150 nm and highly expressed CD9, CD63 and CD81, suggesting the consistence to exosomes. The number of exosomes released by HS hepatocytes was significantly elevated than that in the control group [(8.46±1.38)×109/ml vs. (0.66±0.16)×109/ml, t=5.605, P=0.005]. HS significantly altered the protein expression profile of hepatocyte exosomes, and the enriched proteins were involved in necroptosis, PI3K-Akt signaling, antigen processing and presentation, apoptosis and NOD-like receptor signaling pathways. The supernatant level of ALT/AST/LDH of the recipients' hepatocytes in the HS exosomes-treated group was significantly increased, whereas that in the HS+GW4869 pretreatment group was significantly lower than that in the HS group. The serum ALT/AST/LDH level of the HS exosomes infusion group was significantly enhanced, and that of the pre-HS GW4869 treatment group was significantly reduced than that of the HS group. Conclusion HS may induce the release of exosomes from hepatocytes, which may lead to the changes in the protein profile of exosomes and affect the induction of acute liver injury.
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Objective To characterize exosomes released from human umbilical vein endothelial cells (HUVECs) after heatstroke, and explore their effects on biological behaviors of cells. Methods HUVECs were cultured and divided into the control group and the heat shock group. The heat shock group cells were exposed at 41 ℃ for 2 hours; the control group cells were incubated at 37 ℃ for 2 hours. The characteristics of exosomes secreted by the two groups were analyzed by nanoparticle tracing. The expression of exosomes marker proteins, CD63 and TSG101, were detected by Western blotting. The process of exosomes entering normal cells was observed by fluorescence labeling. To further explore the potential function of exosomes secreted from the heat-shocked cells, cells were co-cultured with exosomes collected from cells cultured at 37 ℃ or cells cultured at 41 ℃. Cells under normal culture conditions were served as a negative control (blank control). FACS was used to detect cell cycle and apoptosis; MTS was used to evaluate cell proliferation; ELISA was used to quantify coagulation related factor expression; high-throughput sequencing was used to profile microRNAs (miRNAs) in the exosomes. Results Different from the control group, the cells in 41 ℃ heat shock group secreted abnormal exosomes, which resulted in abnormal behaviors and functions of normal HUVECs. The expression of tissue factor, von Willebrand factor, plasminogen activator inhibitor-1 increased significantly (P<0.05), and the expression of tissue plasminogen activator decreased (P<0.05). Compared with the incubation of HUVECs at 37 ℃, there were 2590 miRNA regulatory changes in exosomes secreted by HUVECs after heat shock at 41 ℃, which had obvious effects on apoptosis. Conclusions Heat shock at 41 ℃ could induce the release of abnormal exosomes from HUVEC, leading to abnormal behavior and potential coagulation of normal cells.
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[Abstract] Objective To monitor the hyporesponsiveness to norepinephrine in heatstroke rats and the improvement of the responsiveness and inflammation by hydrocortisone. Methods Rats were randomized into 4 groups, saline control group, saline heatstroke group, hydrocortisone control group, and hydrocortisone heatstroke group. The carotid blood pressure was monitored in the four groups of rats under anesthesia. The following three parts of experiments were conducted with the sample size 8 in each part of the experiment. (1) The experiment of noradrenaline at two loading doses (1 μg/kg) i.v.. The mean arterial pressure (MAP) and interval time between blood pressure rising and dropping to the baseline were observed in groups of rats after receiving two loading doses of noradrenaline. (2) The experiment of constant low-dose norepinephrine [25 μg/(kg.h)] by continuous pumping injection. The blood pressure level and survival time were observed. (3) The experiment to detect biochemical indicators related to responsiveness. Four groups of rats receiving constant low-dose norepinephrine were sacrificed, and the serum and aortic tissues were collected to measure serum vasodilators (nitric oxide and prostaglandin E2), hormones (cortisol and adrenocorticotropic hormone), pro-inflammatory factors (nuclear factor κB, tumor necrosis factor α, and interleukin 1β) and α1 adrenergic receptor mRNA expression levels in aortic tissues. Results (1) Compared with the saline control group, the mean arterial pressure and interval time between blood pressure rising and dropping to the baseline were significantly decreased in the saline heatstroke group after receiving noradrenaline injection at a loading dose compared with the normal saline control group, especially after the second dose. The hydrocortisone heatstroke group had higher MAP and longer interval time than the saline heatstroke group. The difference was statistically significant (P<0.05). (2) The mean arterial pressure level of the saline heatstroke group was significantly lower than that of the saline control group after receiving a constant low dose of norepinephrine. The mean arterial pressure in the hydrocortisone heatstroke group was increased compared with the saline heatstroke group, and the survival time was prolonged. The difference was statistically significant (P<0.05). (3) The serum nitric oxide, prostaglandin E2, cortisol, and adrenocorticotropic hormone of the saline heatstroke group were not significantly different from those of the saline control group. The levels of pro-inflammatory factors were significantly increased, and the mRNA levels of α1 adrenergic receptors in the aorta were significantly reduced in the saline heatstroke group compared with the saline control group. The decreased pro-inflammatory factors and increased mRNA of α1 adrenergic receptors in the aorta were observed in the hydrocortisone heatstroke group compared with the saline heatstroke group. The difference was statistically significant (P<0.05). Conclusions The hyporesponsiveness to norepinephrine was demonstrated in the heatstroke rats with circulatory failure. Hydrocortisone could increase MAP and survival time, improve the hyporesponsiveness, reduce the inflammatory cytokines and increase the aortic adrenergic receptor expression.
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Objective To analyze the status of misdiagnosis of exertional heat stroke (EHS), its causes and influence on prognosis. Methods The clinical data of patients with EHS in 9 military hospitals from January 2012 to December 2018 were analyzed retrospectively. According to the time of diagnosis (from onset to the establishment of preliminary or suspected diagnosis), the patients were divided into ≤0.5 h, 0.5-1 h, 1-3 h, 3-6 h and >6 h groups. The number of organs involved and the clinical outcome (death or survival) of patients in each group were recorded, and the relationship between delayed diagnosis and prognostic indexes was analyzed. Through the analysis of misdiagnosis-related medical records, the distribution characteristics and possible causes of misdiagnosis were found. Results Among 122 EHS patients, 23 died, with a total fatality of 18.9%. The diagnosis time showed a skewed distribution, and the median (quartile interval) was 1.5(2.63) h. The correlation analysis between the time of diagnosis and the time of initiation of cooling showed a positive correlation (r=0.871, P<0.05). The number of involved organs increased with the delay of diagnosis, and it was significantly higher in patients diagnosed more than 6 h than that in patients diagnosed in the early stage (within 0.5 h, P<0.05). The risk of death also increased significantly with the delay of diagnosis, and the fatality rate of patients diagnosed more than 6 h was significantly higher than that of patients diagnosed in the early stage (within 0.5 h, P<0.05). The composition ratio of misdiagnosis varied with time. The misdiagnosis rate within 0.5 hours of onset was 87.7%. The diagnosis was mainly based on symptomatic description (64.5%), followed by misdiagnosis as nervous system disease (24.3%). The main causes for the delay in diagnosis were the lack of typical clinical manifestations in the early stage of the disease and the lack of understanding of the disease in the on-site emergency medical personnel. Conclusions The misdiagnosis rate would be high in the early stage of EHS, and it may be significantly related to organ injury and prognosis. The main cause of misdiagnosis in the early stage of EHS might be the lack of understanding of the disease in the on-site emergency medical personnel, which suggests an urgent need to improve the EHS recognition by on-site emergency medical personnel.
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Objective@#To investigate the nursing strategy and curative effect for two kinds of circulating fluid replacement in the treatment of heat stroke (HS) with multiple organ dysfunction (MODS).@*Methods@#The nursing data for 32 patients with HS were analyzed retrospectively. 17 patients of group A were treated with "spend-and-tax" of circulating fluid replacement. 15 patients of group B were treated with conventional fluid replacement. The rehydration fluid was 5% glucose (500ml) and Ringer′s solution (500ml). If necessary, the potassium should be supplemented. The last, to observe the effect of "spend-and-tax" on the outcome of comprehensive treatment of HS combined with MODS.@*Results@#17 patients (group A) were all cured. During treatment, water, electrolyte and acid-base balance disorders did not occur. Comparing with the 15 cases (group B) treated for conventional fluid replacement at same time, the temperature (T), heart rate (HR) were significantly improved (t=-7.453-7.632, all P<0.05), the arterial blood pressures (ABP) were significantly increase (t=-7.896--3.326, all P<0.05).@*Conclusions@#Using the model of "spend-and-tax" fluid replacement can obviously improve the function of liver and kidney, reduce the injury of myocardium and skeletal muscle, improve prognosis, and decrease the mortality rate on patient suffered HS complicated MODS. It was an important content of nursing work that observing and nursing water、electrolytes for patients with HS and MODS.