Heatstroke: a multicenter study in Southwestern China.

Background: An increase in Heatstroke cases occurred in southwest China in 2022 due to factors like global warming, abnormal temperature rise, insufficient power supply, and other contributing factors. This resulted in a notable rise in Heatstroke patients experiencing varying degrees of organ dysfunction. This descriptive study aims to analyze the epidemiology and clinical outcomes of Heatstroke patients in the ICU, providing support for standardized diagnosis and treatment, ultimately enhancing the prognosis of Heatstroke. Methods: A retrospective, multicenter, descriptive analysis was conducted on Heatstroke patients admitted to ICUs across 83 hospitals in southwest China. Electronic medical records were utilized for data collection, encompassing various aspects such as epidemiological factors, onset symptoms, complications, laboratory data, concurrent infections, treatments, and patient outcomes. Results: The dataset primarily comprised classic heatstroke, with 477 males (55% of total). The patient population had a median age of 72 years (range: 63-80 years). The most common initial symptoms were fever, mental or behavioral abnormalities, and fainting. ICU treatment involved respiratory support, antibiotics, sedatives, and other interventions. Among the 700 ICU admissions, 213 patients had no infection, while 487 were diagnosed with infection, predominantly lower respiratory tract infection. Patients presenting with neurological symptoms initially (n = 715) exhibited higher ICU mortality risk compared to those without neurological symptoms (n = 104), with an odds ratio of 2.382 (95% CI 1.665, 4.870) (p = 0.017). Conclusion: In 2022, the majority of Heatstroke patients in southwest China experienced classical Heatstroke, with many acquiring infections upon admission to the ICU. Moreover, Heatstroke can result in diverse complications.

Every Picture Tells A Story: Managing Exertional Heatstroke with Rotating Ice Water Towels.

ABSTRACT: A 23-year-old woman completing her first marathon collapsed near the finish line at 4 hours 6 min with a rectal temperature of 41.8°C. She was in good health before the race with no recent illness, had completed a full training program, and was taking no medications or supplements. On the initial exam, she was unconscious with a response to painful stimulus, spontaneous breathing, rapid pulse, eyes closed, fully dilated pupils, poor muscle tone, and pale skin that was warm to touch. The medical team initiated whole-body cooling using rapidly rotating ice water towels and ice packs placed in the neck, axilla, and groin. She developed echolalia during active cooling. About 20 minutes into the cooling procedure, she "woke up," was able to answer questions coherently, and her pupils were normal size and reactive. She was discharged home with instructions to follow-up in 2 d for evaluation and blood chemistry testing.

Heat exhaustion and heat stroke among active component members of the U.S. Armed Forces, 2019-2023.

The most serious types of heat illnesses, heat exhaustion and heat stroke, are occupational hazards associated with many of the military's training and operational environments. These illnesses can typically be prevented by appropriate situational awareness, risk management strategies, along with effective countermeasures. In 2023, the crude incidence of heat stroke and heat exhaustion were 31.7 and 172.7 cases per 100,000 person-years, respectively. The rates of incident heat stroke declined during the 2019 to 2023 surveillance period, but rates of incident heat exhaustion increased over the same period. In 2023, higher rates of heat stroke were observed among male service members compared to their female counterparts, and female service members experienced higher rates of heat exhaustion compared to male personnel. Heat illness rates were also higher among those younger than age 20, Marine Corps and Army service members, non-Hispanic Black service members, and recruits. Leaders, training cadres, and supporting medical and safety personnel must inform their subordinate and supported service members of heat illness risks, preventive measures, early signs and symptoms of illness, and appropriate interventions.

Monocyte HLA-DR level on admission predicting in-hospital mortality rate in exertional heatstroke: A 12-year retrospective study.

BACKGROUND: Exertional heatstroke (EHS), a fatal illness, pronounces multiple organ dysfunction syndrome (MODS) and high mortality rate. Currently, no ideal factor prognoses EHS. Decreased monocyte human leukocyte-DR antigen (mHLA-DR) has been observed in critically ill individuals, particularly in those with sepsis. While most research focus on the pro-inflammatory response exploration in EHS, there are few studies related to immunosuppression, and no report targeted on mHLA-DR in EHS. The present study tried to explore the prognostic value of mHLA-DR levels in EHS patients. METHODS: This was a single-center retrospective study. Clinical data of EHS patients admitted to the intensive care unit of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. RESULTS: Seventy patients with 54 survivors and 16 nonsurvivors were ultimately enrolled. Levels of mHLA-DR in the nonsurvivors (41.8% [38.1-68.1]%) were significantly lower than those in the survivors (83.1% [67.6-89.4]%, p < 0.001). Multivariate logistic regression indicated that mHLA-DR (odds ratio [OR] = 0.939; 95% confidence interval [CI]: 0.892-0.988; p = 0.016) and Glasgow coma scale (GCS) scores (OR = 0.726; 95% CI: 0.591-0.892; p = 0.002) were independent risk factors related with in-hospital mortality rate in EHS. A nomogram incorporated mHLA-DR with GCS demonstrated excellent discrimination and calibration abilities. Compared to the traditional scoring systems, the prediction model incorporated mHLA-DR with GCS had the highest area under the curve (0.947, 95% CI: [0.865-0.986]) and Youden index (0.8333), with sensitivity of 100% and specificity of 83.33%, and a greater clinical net benefit. CONCLUSION: Patients with EHS were at a risk of early experiencing decreased mHLA-DR early. A nomogram based on mHLA-DR with GCS was developed to facilitate early identification and timely treatment of individuals with potentially poor prognosis.

Heat stress induces IL-1ß and IL-18 overproduction via ROS-activated NLRP3 inflammasome: implication in neuroinflammation in mice with heat stroke.

Heat stroke induced cerebral damage via neuroinflammation. This study aimed to approach whether heat stress would promote NOD-like receptor protein 3 (NLRP3) inflammasome via reactive oxygen species (ROS). The mice were randomly divided into the sham group, the heat stress group, and the heat stress + TEMPOL (ROS scavenger) group. And the NLRP3 -/- mice were applied and divided into the NLRP3 -/-  + sham group and the NLRP3 -/-  + heat stress group. Furthermore, the BV2 cells were divided into four groups following the intervention measures: the heat stress + TEMPOL group, the heat stress + Z-VAD-FMK (caspase-1 inhibitor) group, the heat stress group, and the control group. ROS levels were examined. The expression levels of NLRP3, caspase-1, IL-1ß, and IL-18 were detected by western blotting and double immunofluorescence. We found that heat stress attack induced excessive ROS in microglia and subsequently activated NLRP3 inflammasome in both mice and BV2 cells. When ROS scavenged, the expression level of NLRP3 was downregulated. Furthermore, with NLRP3 inflammasome activation, the expression levels of caspase-1, IL-1ß, and IL-18 were increased. In NLRP3 -/- mice, however, the caspase-1, IL-1ß, and IL-18 were significantly declined. Further experiments showed that pretreatment of caspase-1 inhibitor decreased the expression levels of IL-1ß and IL-18. These results suggest that heat stress attack caused neuroinflammation via excessive ROS activating the NLRP3 inflammasome in microglia cells.

Risk factors for and outcomes of heatstroke-related intracerebral hemorrhage.

Some patients with heatstroke also experience intracerebral hemorrhage (ICH). However, clinical case reports of heatstroke-induced ICH are rare. The risk factors for cerebral hemorrhage after heatstroke remain unknown. The present study evaluated the clinical characteristics and risk factors of patients with heatstroke-related ICH. In this retrospective observational study, we collected data on all ICHs after heatstroke occurred between 2012 and 2022. The characteristics of patients with heatstroke-induced ICH were described. The risk factors for cerebral hemorrhage after heatstroke were examined using logistic regression analysis. In total, 177 patients were included in this study, and 11 patients with ICH secondary to heatstroke were identified. Variables with P values of <.05 in univariate models, comparing the cerebral hemorrhage and control groups, included heatstroke cause, temperature, heart rate, respiratory rate, vasopressor use, mechanical ventilation use, Acute Physiology and Chronic Health Evaluation II, total bilirubin, creatinine, platelet count, prothrombin time, procalcitonin, creatine kinase, disseminated intravascular coagulation (DIC) occurrence, and DIC score. Multivariate logistic regression showed that heatstroke patients with higher DIC scores (odds ratio, 18.402, 95% confidence interval, 1.384-244.763, P = .027) and higher creatine kinase levels (odds ratio, 1.021, 95% confidence interval, 1.002-1.041, P = .033) were at a higher risk of developing ICH. The death rate was higher in the cerebral hemorrhage group than in the control group (P = .042). Heatstroke-related cerebral hemorrhage may be associated with elevated creatinine levels and DIC severity (International Society on Thrombosis and Hemostasis score) after heatstroke, and heatstroke with cerebral hemorrhage may accelerate death.

[Constructing an early-warning model for mortality risk in heat stroke patients based on Fisher discriminant analysis].

Objective: To establish an early warning model to assess the mortality risk of patients with heat stroke disease. Methods: The case data of patients diagnosed with heat stroke disease admitted to the comprehensive ICU of Shanshan County from January 2016 to December 2020 were selected. According to the short-term outcome (28 days) of patients, they were divided into death group (20 cases) and survival group (53 cases) . The relevant indicators with statistically significant differences between groups within 24 hours after admission were selected. By drawing the subject work curve (ROC) and calculating the area under the curve, the relevant indicators with the area under the curve greater than 0.7 were selected, Fisher discriminant analysis was used to establish an assessment model for the death risk of heat stroke disease. The data of heat stroke patients from January 1, 2021 to December 2022 in the comprehensive ICU of Shanshan County were collected for external verification. Results There were significant differences in age, cystatin C, procalcitonin, platelet count, CKMB, CK, CREA, PT, TT, APTT, heart rate, respiratory rate and GLS score among the groups. Cystatin C, CKMB, CREA, PT, TT, heart rate AUC area at admission was greater than 0.7. Fisher analysis method is used to build a functional model. Results: The diagnostic sensitivity, specificity and AUC area of the functional model were 95%, 83% and 0.937 respectively. The external validation results showed that the accuracy of predicting survival group was 85.71%, the accuracy of predicting death group was 88.89%. Conclusion: The early warning model of heat stroke death constructed by ROC curve analysis and Fisher discriminant analysis can provide objective reference for early intervention of heat stroke.

Exertional heat stroke-induced changes in gut microbiota cause cognitive impairment in mice.

BACKGROUND: The incidence of exertional heat stroke (EHS) escalates during periods of elevated temperatures, potentially leading to persistent cognitive impairment postrecovery. Currently, effective prophylactic or therapeutic measures against EHS are nonexistent. METHODS: The selection of days 14 and 23 postinduction for detailed examination was guided by TEM of neuronal cells and HE staining of intestinal villi and the hippocampal regions. Fecal specimens from the ileum and cecum at these designated times were analyzed for changes in gut microbiota and metabolic products. Bioinformatic analyses facilitated the identification of pivotal microbial species and metabolites. The influence of supplementing these identified microorganisms on behavioral outcomes and the expression of functional proteins within the hippocampus was subsequently assessed. RESULTS: TEM analyses of neurons, coupled with HE staining of intestinal villi and the hippocampal region, indicated substantial recovery in intestinal morphology and neuronal injury on Day 14, indicating this time point for subsequent microbial and metabolomic analyses. Notably, a reduction in the Lactobacillaceae family, particularly Lactobacillus murinus, was observed. Functional annotation of 16S rDNA sequences suggested diminished lipid metabolism and glycan biosynthesis and metabolism in EHS models. Mice receiving this intervention (EHS + probiotics group) exhibited markedly reduced cognitive impairment and increased expression of BDNF/TrKB pathway molecules in the hippocampus during behavioral assessment on Day 28. CONCLUSION: Probiotic supplementation, specifically with Lactobacillus spp., appears to mitigate EHS-induced cognitive impairment, potentially through the modulation of the BDNF/TrKB signaling pathway within the hippocampus, illustrating the therapeutic potential of targeting the gut-brain axis.

Experimental and numerical investigation of thermal environment of the child trapped in a parked vehicle.

Pediatric vehicular hyperthermia (PVH) has aroused wide public concern recently. High temperatures in closed vehicles with full sun exposure and no ventilation in summer seriously endanger children's lives. Aiming at this practical problem, this study first took the temperature of child's core body as a standard, and divided the hyperthermia into three stages: un-compensable heating (Tc > 37ºC), heat stroke (Tc > 40ºC) and critical thermal maximum (Tc > 42ºC). On this basis, two weeks of outdoor parking experiments during 10:00-18:00, using an equivalent size dummy were conducted to explore the influence of ambient temperature and solar irradiation on cabin temperature, humidity, and child's core body temperature. According to the experimental results, at an ambient temperature of 32.4ºC, the child in the cabin developed un-compensable heating within 72 min, suffered heat stroke within 129 min, and reached the critical thermal maximum within 151 min. Considering the limitations of the experiment, a numerical study was conducted to analyze the effects of ambient temperature, solar irradiation, and window radiation characteristics on cabin temperature and flow fields comprehensively. Simulation results were in good agreement with the experiments: even at low ambient temperature Ta = 23ºC or weak solar irradiation (ts = 18:00) condition, the temperature in a closed compartment could reach the "hazardous" level. This study can provide guidance for public to increase security and prevention awareness, and promote the development of relevant policies and technologies.

Heat Stroke Induces Pyroptosis in Spermatogonia via the cGAS-STING Signaling Pathway.

To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING). After STING silencing by siRNA, the expressions of pyroptosis-related proteins were determined. Pyroptosis occurred after heat stimulation of cells. Morphological detection found cell swelling and karyopyknosis. According to the gamma-H2AX immunofluorescence (IFA) assay, the endonuclear green fluorescence was significantly enhanced, the gamma-H2AX content markedly increased, and the endonuclear DNA was damaged. Flow cytometry revealed a significant increase in pyroptosis index. Western blot and PCR assays showed that the expressions of intracellular pyrogenic proteins like Caspase-1, NLRP3 and GSDMD were elevated. The increased STING protein and gene expressions in cGAS-STING pathway suggested that the pathway was intracellularly activated. Silencing STING protein in cGAS-STING pathway led to significantly inhibited pyroptosis. These results indicate that cGAS-STING pathway plays an important role in heat stress-induced pyroptosis of spermatogonial cells. After heat stimulation of spermatogonial GC-1 cells, pyroptosis was induced and cGAS-STING pathway was activated. This study can further enrich and improve the molecular mechanism of cryptorchidism.

Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response.

Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P < 0.05). These index values in the L-AS, M-AS, and H-AS groups were significantly lower than those in the DHC group (P < 0.05). The index values decreased significantly with an increase in the concentration of isorhamnetin (P < 0.05), while the index values of CAT and SOD showed the opposite tendency (P < 0.05). The expression of liver tissue nuclear factor kappa B (NF-κB), caspase-3, and heat shock protein (HSP-70) was higher in the DHC group than in the NC group (P < 0.05). Comparison between the isorhamnetin and DHC groups revealed that the expression of NF-кB and caspase-3 was decreased, while that of HSP-70 continued to increase (P < 0.05). The difference was significant for HSP-70 among all the isorhamnetin groups (P < 0.05); however, the NF-кB and caspase-3 values in the L-AS and H-AS groups did not differ. In summary, isorhamnetin has protective effects against liver injury in heat-stroke-affected rats. This protective effect may be related to its activities concerning antioxidative stress, anti-inflammatory response, inhibition of NF-кB and caspase-3 expression, and enhancement of HSP-70 expression.

DNAJA1­knockout alleviates heat stroke­induced endothelial barrier disruption via improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Endothelial barrier disruption plays a key role in the pathophysiology of heat stroke (HS). Knockout of DNAJA1 (DNAJA1­KO) is thought to be protective against HS based on a genome­wide CRISPR­Cas9 screen experiment. The present study aimed to illustrate the function of DNAJA1­KO against HS in human umbilical vein endothelial cells. DNAJA1­KO cells were infected using a lentivirus to investigate the role of DNAJA1­KO in HS­induced endothelial barrier disruption. It was shown that DNAJA1­KO could ameliorate decreased cell viability and increased cell injury, according to the results of Cell Counting Kit­8 and lactate dehydrogenase assays. Moreover, HS­induced endothelial cell apoptosis was inhibited by DNAJA1­KO, as indicated by Annexin V­FITC/PI staining and cleaved­caspase­3 expression using flow cytometry and western blotting, respectively. Furthermore, the endothelial barrier function, as measured by transepithelial electrical resistance and FITC­Dextran, was sustained during HS. DNAJA1­KO was not found to have a significant effect on the expression and distribution of cell junction proteins under normal conditions without HS. However, DNAJA1­KO could effectively protect the HS­induced decrease in the expression and distribution of cell junction proteins, including zonula occludens­1, claudin­5, junctional adhesion molecule A and occludin. A total of 4,394 proteins were identified using proteomic analysis, of which 102 differentially expressed proteins (DEPs) were activated in HS­induced wild­type cells and inhibited by DNAJA1­KO. DEPs were investigated by enrichment analysis, which demonstrated significant enrichment in the 'calcium signaling pathway' and associations with vascular­barrier regulation. Furthermore, the 'myosin light­chain kinase (MLCK)­MLC signaling pathway' was proven to be activated by HS and inhibited by DNAJA1­KO, as expected. Moreover, DNAJA1­KO mice and a HS mouse model were established to demonstrate the protective effects on endothelial barrier in vivo. In conclusion, the results of the present study suggested that DNAJA1­KO alleviates HS­induced endothelial barrier disruption by improving thermal tolerance and suppressing the MLCK­MLC signaling pathway.

Hyperthermia: Is it always an accidental death?

INTRODUCTION: The research aimed to determine individual variations in different core temperature measurements before the experiment, after submersion, after 20 min of exposure for heat stroke. METHODS: Rats were divided into three groups depending on the temperature and length of exposure to water: CG, G41-20 and G41-UD. The protocol was made according to the earlier described methodology of heat shock induction. RESULTS: A significant difference was observed in the G41-UD group; p < 0.0005. The lowest body temperature of the rats was observed, from normothermia, and the highest temperature after death, 37.87 ± 0.62 °C vs 41.20 ± 0.76 °C, the difference between all three groups is p < 0.0005. CONCLUSION: Exposure of Wistar rats to water temperatures in the CG and G41 groups led to a significant change in core temperature. In the control group, the thermoregulatory mechanism firmly established normothermia, while hyperthermia was revealed in the G41 group during the 20-minute exposure.

Hyperbaric oxygen preconditioning normalizes scrotal temperature, sperm quality, testicular structure, and erectile function in adult male rats subjected to exertional heat injury.

Testicular hyperthermia has been noted in men who work in high ambient temperatures. Scrotal temperatures above the normal range caused germ cell loss in the testes and resulted in male subfertility. In adult male rats, exercising at a higher environmental temperature (36 °C with relative humidity of 50%, 52 min) caused exertional heat stroke (EHS) characterized by scrotal hyperthermia, impaired sperm quality, dysmorphology in testes, prostates and bladders, and erectile dysfunction. Here, we aim to ascertain whether hyperbaric oxygen preconditioning (HBOP: 100% O2 at 2.0 atm absolute [ATA] for 2 h daily for 14 days consequently before the onset of EHS) is able to prevent the problem of EHS-induced sterility, testes, prostates, and bladders dysmorphology and erectile dysfunction. At the end of exertional heat stress compared to normobaric air (NBA or non-HBOP) rats, the HBOP rats exhibited lower body core temperature (40 °C vs. 43 °C), lower scrotal temperature (34 °C vs. 36 °C), lower neurological severity scores (2.8 vs. 5.8), higher erectile ability, (5984 mmHg-sec vs. 3788 mmHg-sec), higher plasma testosterone (6.8 ng/mL vs. 3.5 ng/mL), lower plasma follicle stimulating hormone (196.3 mIU/mL vs. 513.8 mIU/mL), lower plasma luteinizing hormone (131 IU/L vs. 189 IU/L), lower plasma adrenocorticotropic hormone (5136 pg/mL vs. 6129 pg/mL), lower plasma corticosterone (0.56 ng/mL vs. 1.18 ng/mL), lower sperm loss and lower values of histopathological scores for epididymis, testis, seminal vesicle, prostate, and bladder. Our data suggest that HBOP reduces body core and scrotal hyperthermia and improves sperm loss, testis/prostate/bladder dysmorphology, and erectile dysfunction after EHS in rats.

Heat stroke-induced cerebral cortex nerve injury by mitochondrial dysfunction: A comprehensive multi-omics profiling analysis.

In recent years, global warming has led to frequent instances of extremely high temperatures during summer, arousing significant concern about the adverse effects of high temperature. Among these, heat stroke is the most serious, which has detrimental effects on the all organs of human body, especially on brain. However, the comprehensive pathogenesis leading to brain damage remains unclear. In this study, we constructed a mouse model of heat stroke and conducted multi-omics profiling to identify relevant pathogenesis induced by heat stroke. The mice were placed in a constant temperature chamber at 42 °C with a humidity of 50 %, and the criteria for success in modeling were that the rectal temperature reached 42 °C and that the mice were trembling. Then the mice were immediately taken out for further experiments. Firstly, we conducted cFos protein localization and identified the cerebral cortex, especially the anterior cingulate cortex as the region exhibiting the most pronounced damage. Secondly, we performed metabolomics, transcriptomics, and proteomics analysis on cerebral cortex. This multi-omics investigation unveiled noteworthy alterations in proteins and metabolites within pathways associated with neurotransmitter systems, heatstroke-induced mitochondrial dysfunction, encompassing histidine and pentose phosphate metabolic pathways, as well as oxidative stress. In addition, the cerebral cortex exhibited pronounced Reactive Oxygen Species (ROS) production, alongside significant downregulation of the mitochondrial outer membrane protein Tomm40 and mitochondrial permeability transition pore, implicating cerebral cortex mitochondrial dysfunction as the primary instigator of neural impairment. This study marks a significant milestone as the first to employ multi-omics analysis in exploring the molecular mechanisms underlying heat stroke-induced damage in cerebral cortex neurons. It comprehensively identifies all potentially impacted pathways by heat stroke, laying a solid foundation for ensuing research endeavors. Consequently, this study introduces a fresh angle to clinical approaches in heatstroke prevention and treatment, as well as establishes an innovative groundwork for shaping future-forward environmental policies.

Gender disparities in summer outdoor heat risk across China: Findings from a national county-level assessment during 1991-2020.

Increasing anthropogenic global warming has emerged as a significant challenge to human health in China, as extreme heat hazards increasingly threaten outdoor-exposed populations. Differences in thermal comfort, outdoor activity duration, and social vulnerability between females and males may exacerbate gender inequalities in heat-related health risks, which have been overlooked by previous studies. Here, we combine three heat hazards and outdoor activity duration to identify the spatiotemporal variation in gender-specific heat risk in China during 1991-2020. We found that females' heat risk tends to be higher than that of males. Gender disparities in heat risk decrease in southern regions, while those in northern regions remain severe. Males are prone to overheating in highly urbanized areas, while females in low urbanized areas. Males' overheating risk is mainly attributed to population clustering associated with prolonged outdoor activity time and skewed social resource allocation. In contrast, females' overheating risk is primarily affected by social inequalities. Our findings suggest that China needs to further diminish gender disparities and accelerate climate adaptation planning.