Objective To compare the effects of different exercise acclimatization (EA) durations on liver injury and inflammatory response in mice with exertional heatstroke (EHS). Methods A total of 168 male C57BL/6 mice were randomly assigned to four groups using a random number table: no exercise acclimation group (EA0W, n=54), 1-week exercise acclimation group (EA1W, n=54), 2-week exercise acclimation group (EA2W, n=54), and blank control group (n=6). The blank control group did not undergo acclimatization training or EHS modeling. The EA1W and EA2W groups underwent daily 2-hour exercise training at a speed of 10 m/min in an environment maintained at (26.0±0.5) ℃ for 1 and 2 weeks, respectively, followed by a 2-day rest after training completion. EHS modeling was performed in mice of EA0W, EA1W, and EA2W groups through running at 10 m/min under controlled environmental conditions (39.5 ℃ ambient temperature, 65% relative humidity). The modeling endpoint was defined as loss of consciousness accompanied by a core body temperature ≥42.7 ℃. All modeling procedures were systematically documented. Following modeling, 18 mice from EA0W, EA1W, and EA2W groups underwent 24-hour survival analysis. Blood samples from the abdominal aorta and liver tissues were collected at 6, 12 and 24 hours post-modeling (6 mice per time point for each group). Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK) were quantified. Interleukin (IL)-1β and IL-6 concentrations were determined using enzyme-linked immunosorbent assay (ELISA). Liver tissue specimens underwent hematoxylin-eosin (HE) staining and pathological scoring. Results The EHS model was successfully established in all EA groups. When all mice in EA0W group developed EHS (65 min after the modeling initiation), the incidence rates in EA1W and EA2W groups were 50.0% and 22.2%, respectively, with a statistically significant difference between EA0W group and the latter two groups (P<0.05). When all mice in the three groups developed EHS, the time to EHS onset was significantly longer in both EA1W and EA2W groups compared to EA0W group, with EA2W group showing a longer onset time than EA1W group (P<0.05). Survival analysis revealed a significantly higher 24-hour survival rate in EA2W group (61.1%) compared to EA0W group (33.3%) (P<0.05), while no significant difference was observed between EA1W group and the other two groups (P>0.05). The levels of IL-1β, IL-6, and CK were highest at 6 h post-modeling in all EA groups (P<0.05), and liver injury was most severe at 12 h post-modeling (P<0.05). Compared to EA0W group, the levels of ALT, AST, and IL-1β, as well as liver pathology scores, were significantly lower at 12 h post-modeling in both EA1W and EA2W groups (P<0.05), with EA2W group showing significantly lower ALT and AST levels, as well as liver pathology scores than EA1W group (P<0.05). At 6 h post-modeling, CK levels were significantly higher in EA1W and EA2W groups compared to EA0W group (P<0.05), with EA2W group exhibiting higher CK levels than in EA1W group (P<0.05). Conclusions Exercise acclimation helps reduce the incidence of EHS. Following EHS onset, the survival rate of exercise-acclimated mice is higher than that non-acclimated mice, with a significantly higher survival rate in mice acclimated for 2 weeks compared to non-acclimated mice. However, no significant difference in survival rate is observed between mice acclimated for 1 week and non-acclimated mice. Additionally, exercise acclimation for 2 weeks is more effective in reducing liver injury and inflammatory responses compared to 1-week acclimation.

Good endometrial receptivity is an essential factor for embryo implantation, and gene expression in endometrial tissue during the window of implantation (WOI) is closely related to receptivity. Transcriptome sequencing technology enables the identification of gene expression profiles of endometrium during different menstrual phases, as well as microRNAs and long-chain non-coding RNA sequences involved in regulating gene expression. Combining this technology with bioinformatics analysis provides a better understanding of specific gene expression during the receptive period and offers technical support for studying its regulatory mechanism. Moreover, gene expression profiles of the endometrium during different menstrual phases hold significant clinical application value for accurately assessing endometrium receptivity in infertility patients and those with repeated implantation failure, thereby guiding individualized embryo transfer strategies. This review summarizes the progress of transcriptome sequencing in evaluating human endometrial receptivity and discusses future research directions. This review aims to understand the complex molecular mechanisms of endometrial receptivity formation and regulation from the transcriptional level, in order to improve the implantation rate of embryos in assisted reproductive technology and reduce the abortion rate.

White matter hyperintensities (WMH) are abnormal high-signal manifestations in white matter areas on magnetic resonance T₂-weighted or fluid-attenuated inversion recovery (FLAIR) sequences, with vasogenic WMH being the most common. Its pathological mechanism is related to cerebrovascular lesions and can lead to multi-dimensional brain functional impairments in cognition, movement, and emotions. Due to their unique working conditions, aircrews are more prone to vasogenic WMH than the general population. Moreover, with the widespread use of magnetic resonance imaging in cranial disease screening for aircrews, the detection rate of vasogenic WMH in aircrews has significantly increased. However, to date, no national or academic organization has issued standardized aviation medical assessment criteria for vasogenic WMH in aircrews. Therefore, led by Xijing Hospital of Air Force Medical University and the Chinese PLA General Hospital, a multi-disciplinary expert panel involved in aviation medicine, neurology, radiology, psychology, and related fields was assembled to formulate this consensus. The document integrates evidence from a systematic review of PubMed, CNKI, Wanfang Data, and VIP databases, incorporates existing WMH guidelines, and synthesizes clinical expertise from Chinese specialists. The consensus outlines three key domains: target population, neuroimaging protocols for vasogenic WMH screening, and clinical assessment and aeromedical identification for aircrews with vasogenic WMH. The aim is to provide evidence-based support and expert recommendations for standardizing and improving the accuracy of aviation medical evaluations of vasogenic WMH in aircrews.

Alzheimer's disease (AD), a major cause of dementia, is a common neurodegenerative disease, beginning with memory loss and difficulties with thinking, language and problem-solving skills. Intensification of population aging and the increasing incidence of AD have imposed a heavy burden on healthcare systems. Currently, the main pathological explanation remains the excessive accumulation of β‑amyloid plaques, formation of neurofibrillary tangles and neuronal loss, but the true etiology and pathogenesis of AD remain unknown. The advances of research in AD, with respect to genetics, pathophysiological mechanism, imaging diagnosis and laboratory diagnosis, are reviewed in this article, aiming to provide references for relevant research and potential clinical applications.

Objective To investigate the predictive value of temperature gradients on the mortality of sepsis patients and their correlation with fluid input. Methods By means of a prospective observational method, 154 patients with sepsis or septic shock admitted to the Department of Critical Care Medicine at Nanfang Hospital, Southern Medical University from November 2019 to November 2021 were included as research subjects. They were divided into a survivor group (n=118) and a non-survivor group (n=36) according to whether they survived within 28 days. The core-to-toe temperature gradient (CTTG) and toe-to-room temperature gradient (TRTG) were monitored and calculated immediately upon admission to the intensive care unit (ICU) and 6 hours after admission. Receiver operating characteristic (ROC) curve was used to explore the predictive value of temperature gradients on mortality, and multivariate Cox regression analysis was performed to explore the risk factors of 28-day mortality in sepsis patients. The results were verified through survival analysis. Correlation analysis and multivariate analysis of variance were used to explore the correlation between temperature gradients and fluid input, as well as noradrenaline doses. Results Among the 154 patients, 118 survived within 28 days (survivor group), and 36 died (non-survivor group). ROC curve and multivariate Cox regression analysis showed that a toe-to-room temperature gradient of ≤5.35 ℃ within 6 hours after admission was a risk factor for 28-day mortality. Compared with patients with a high toe-to-room temperature gradient (>5.35 ℃), patients with a low toe-to-room temperature gradient (≤5.35 ℃) had a 2.74-fold increase in the risk of 28-day mortality (P=0.004, 95%CI 1.54, 9.12). The CTTG and TRTG upon admission to the ICU and 6 hours after admission were not significantly associated with fluid input or noradrenaline doses (P>0.05). Conclusions A toe-to-room temperature gradient of less than or equal to 5.35 ℃ within 6 hours after ICU admission is a risk factor for 28-day mortality in sepsis patients. The improvement of temperature gradients at different time points is not associated with fluid input.

Objective To investigate the effects of a 100 mT static magnetic field (SMF) on emotional behavior and brain damage-related molecules in mice. Methods Fifty-eight C57BL/6N mice were randomly divided into control group (n=25) and observation group (n=33). Mice in observation group were exposed to a 100 mT SMF for 0.5 h/d over 14 consecutive days, while mice in control group underwent pseudo-exposure. On the 7 and 14 days of exposure, anxiety-like behavior was assessed using open field and elevated plus maze tests. Cerebral blood flow was monitored using laser speckle imaging, and the levels of tumor necrosis factor-α(TNF-α), interleukin (IL)-1β, IL-4, central nervous system specific protein β (S100β), neuron-specific enolase (NSE), and brain-derived neurotrophic factor (BDNF) were measured by radioimmunoassay. BDNF expression in the brain was detected by immunofluorescence. Results On the 7 and 14 days of SMF exposure, the open field and elevated plus maze tests showed no statistically significant differences between observation and control groups in the frequencies, durations, and distance entering the central area of the open field and the open arm of the elevated plus maze (P>0.05). Laser speckle imaging revealed no significant difference in cerebral cortical perfusion compared with pre-exposure period (P>0.05). The results of radioimmunoassay showed that compared with control group, on the 7 d of SMF exposure, the serum IL-1β, NSE and S100β levels were significantly increased (P<0.05), the serum BDNF level was significantly decreased (P<0.05), and the IL-1β and TNF-α contents in brain tissues were significantly increased in observation group (P<0.01). On the 14 d of SMF exposure, serum IL-1β, TNF‑α, NSE, and S100β levels were significantly increased (P<0.05, P<0.0001), and the brain IL-1β and TNF‑α levels were significantly increased (P<0.01) in observation group. No statistically significant differences were found in anti-inflammatory cytokine IL-4 level of serum and brain tissue or BDNF content of brain tissue between the two groups (P>0.05). Conclusion Continuous exposure to a 100 mT SMF for 14 d at 0.5 h/d induces neuroinflammation and brain damage in mice, without inducing anxiety-like behavior.

Objective To investigate the effects of advanced maternal age (AMA) on synaptic pruning of the hippocampus of offspring rats. Methods Offspring of 3-month-old SD female rats and 3-month-old SD male rats were designated as the appropriate age group (Ctl group), while offspring of 12-month-old SD female rats and 3-month-old SD male rats were assigned to AMA group. Hippocampal tissues from both groups (n=3 per group at each time point) were subjected to Golgi staining on postnatal days (P) 7, 28, and 60. Dendritic complexity, spine density (DS), and morphology of immature brain neurons at different age stages were compared between the two groups. Results Compared with Ctl group, the dendritic length of AMA group on P7, P28, and P60 was significantly shortened, and the average number of intersections between dendrites and concentric circles on P28 and P60 was also significantly decreased (P<0.05). Compared with Ctl group, the dendritic spine density of AMA group was significantly decreased on P7, P28, and P60. Notably, the density of thin-shaped dendritic spines in AMA group was increased on P7, whereas the densities of stubby-shaped and mushroom-shaped dendritic spines were decreased (P<0.05). On P28 in AMA group, the densities of thin-shaped and mushroom-shaped dendritic spines were significantly increased compared with Ctl group, while the density of stubby-shaped dendritic spines was significantly decreased (P<0.05). The densities of stubby-shaped and mushroom-shaped dendritic spine were markedly lower in AMA group on P60 than those in Ctl group (P<0.05). Conclusions During postnatal brain development periods, there were abnormalities in synaptic pruning in the hippocampal region of the offspring of the AMA, which manifested as reduced dendritic complexity, decreased dendritic spine density, and disorganized dendritic spine morphology. It could be one of the key mechanisms underlying brain dysfunction in the offspring of AMA.

The neurovascular unit (NVU) is the smallest structural unit that maintains the integrity of the blood-brain barrier (BBB), regulates cerebral physiological activities, and maintains the homeostasis of the brain's internal environment. It has become a hot topic in the study of brain physiology and pathological changes. NVU plays a crucial role in age-dependent central nervous system diseases such as cerebral white matter lesions, cognitive impairment, and cerebrovascular disease. Its dysfunction can lead to destruction of BBB integrity, with subsequent protein leakage, immune-inflammatory responses, and alterations in cerebral hemodynamics, all of which can trigger seizures or progression of neurodegenerative disorders. Conversely, seizures can also accelerate NVU dysfunction and promote brain aging. The review summarizes the role of dysfunctional constituent cells of the NVU in the pathogenesis of age-dependent epilepsy and the research progress in related molecular pathways, aiming to provide new perspectives for epilepsy treatment research.

Objective To investigate application value of three-dimensional light sheet microscopy imaging for evaluating intraplaque neovascularization in arterial plaques and the efficacy of intervention, and to assess the effect of melatonin (MLT) on neovascularization by these means. Methods Thirty-six ApoE^-/- model mice were randomly divided into three groups (n=12): vehicle group, MLT group, and MLT+GW9662 intervention group (MLT+GW). The mice were treated with vehicle, MLT alone, or MLT combined with peroxisome proliferator activated receptor‑γ (PPARγ) inhibitor GW9662, respectively. The carotid arteries of the models were three-dimensionally imaged using a light sheet microscopy, and the length, volume and other indicators of neovascularization were quantitatively analyzed using Imaris software. Subsequently, CD31 immunohistochemical staining was performed for verification. Results The light sheet microscopy preliminarily achieved the three-dimensional visualization of intraplaque neovascularization, and its structure was observed to be three-dimensionally reticular and scattered. The results of Imaris quantitative analysis showed that, compared with vehicle group, the total intraplaque neovas cularization length in the MLT group was shortened [(15.79±12.90) mm vs. (33.42±11.16) mm, P<0.05], the total volume was reduced [(1.34±1.47)×10^-3 mm³ vs. (13.44±7.35)×10^-3 mm³, P<0.05], and the volume ratio was decreased (0.44%±0.47% vs. 3.76%±1.74%, P<0.05). The above indicators in MLT+GW group were significantly increased compared with those in MLT group [total length: (35.31±4.69) mm, total volume: (8.87±3.46)×10^-3 mm³, volume ratio: 2.89%±0.38%; P<0.05]. The CD31 immunohistochemical staining also supported the above findings (P<0.05). Conclusions Based on the light sheet microscopy imaging technology, the three-dimensional visualization and quantitative analysis of intraplaque neovascularization were preliminarily realized. It was found that MLT could reduce the overall burden of intraplaque neovascularization, and PPARγ might be involved in its regulatory process.

Objective To investigate the effect of total paeony glycoside (TPG) on airway remodeling in bronchial asthma mice and its underlying mechanisms. Methods Forty-eight BALB/c mice were randomly divided into control group, model group, ovalbumin+budesonide group (OVA+BUD group), and OVA+TPG group, with 12 mice in each group. Except the control group, mice in other groups were sensitized by intraperitoneal injection of 10% OVA aluminum hydroxide suspension, and then stimulated by atomized inhalation of 1% OVA to establish mouse asthma model. One hour before each inhalation of OVA, mice in OVA+BUD group were atomized with 2 ml BUD suspension, and mice in OVA+TPG group were given 5 g/kg TPG by intragastric administration. Lung tissues and bronchoalveolar lavage fluid (BALF) of mice from each group were collected, and the pathological morphology of the lung tissues was detected by hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining. Inflammatory cell counts [white blood cell (WBC), neutrophil (NEU), eosinophils (EOS), and leukomonocyte (LYM)] in BALF were detected by Wright-giemsa staining. The contents of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in BALF were determined by ELISA. Airway remodeling proteins [fibronectin, α-smooth muscle actin (α-SMA), collagen Ⅰ] and NOD-like receptor protein 3 (NLRP3) inflammasome-related proteins [NLRP3, cleaved caspase-1, apoptosis-associated speck-like protein (ASC)] levels were detected by Western blotting. Human bronchial smooth muscle cells (HBSMCs) were divided into control group (normal culture), transforming growth factor (TGF)-β₁ group (culture medium containing 10 ng/ml TGF-β₁), and TGF-β₁+TPG group (culture medium containing 10 ng/ml TGF-β₁ and 50 µg/ml TPG). Cell proliferation was detected by CCK-8 method, and Western blotting was used to detect the expression of airway remodeling proteins and NLRP3 inflammasome-related proteins. Results Compared with control group, model group exhibited increased infiltration of inflammatory cell in lung tissues, mucosal epithelium hyperplasia, narrowed bronchial lumen narrowed, tube wall thickened, increased cup cells and mucus secretion, and an elevated pathological score of lung injury (P<0.05); the number of inflammatory cells (WBC, NEU, EOS, and LYM) and the levels of inflammatory factors (TNF-α, IL-1β, and IL-6) in BALF were increased (P<0.05), and the expressions of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC were elevated (P<0.05). Compared with model group, BUD or TPG treatment effectively reduced asthma symptoms, improved lung histopathology injury, inhibited bronchial wall thickening, significantly reduced the number of inflammatory cells (WBC, NEU, EOS, and LYM) and the content of inflammatory factors (TNF-α, IL-1β, and IL-6) in BALF, and inhibited expression of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC (P<0.05). Compared with control group, the proliferation rate of HBSMCs was increased, and the protein expression levels of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC were increased in TGF-β₁ group (P<0.05). Compared with TGF-β₁ group, TPG treatment decreased cell proliferation and inhibited the protein expression of fibronectin, α-SMA, collagen Ⅰ, NLRP3, cleaved caspase-1 and ASC (P<0.05). Conclusion TPG may alleviate airway remodeling and asthma symptoms by decreasing the expression of airway remodeling-related proteins, inhibiting NLRP3 inflammasome activation, and reducing the inflammatory response.