Acute mountain sickness (AMS) is a major health issue for people travelling to high altitudes. This study was designed to comprehensively evaluate the changes in clinical characteristics and biochemical indices of high-altitude travelers and determine whether these changes were associated with AMS. A total of 14 clinical indices and 52 biochemical indices were determined in 22 subjects before and during acute high-altitude exposure. Six hours after passive ascent to 3648 m (Lhasa, China), the Lake Louise Scoring (LLS) system 2018 was used to assess AMS, which was defined as headache with a total LLS ≥3. Before travelling to high altitudes, uric acid (UA), platelet distribution width (PDW), mitral peak E velocity (MVE), and ejection fraction (EF) were significantly higher in AMS-resistant individuals than in AMS-susceptible ones (all p < 0.05). A good predictive value of UA (0.817, 95% CI: 0.607-1.000) and PDW (0.844, 95% CI: 0.646-1.000) for AMS-susceptible subjects was found. With high-altitude experience, 14 subjects were diagnosed as having AMS. Compared with non-AMS, the changes in UA and number of neutrophils in AMS presented a significant difference (all p < 0.05). The high-altitude-induced changes in UA, area under the curve, specificity, and sensitivity for identifying AMS were 0.883 (95% CI: 0.738-1.000), 83.30%, and 90.00%, respectively. Human presents a compensatory physiological and biochemical response to high-altitude travel at early phase. The UA concentration before travel and its trend with high-altitude experience exhibited good performance for identifying AMS.

Bisphosphoglycerate mutase (BPGM) is expressed in human erythrocytes and responsible for the production of 2,3-bisphosphoglycerate (2,3-DPG). However, the expression and role of BPGM in other cells have not been reported. In this work, we found that BPGM was significantly upregulated in astrocytes upon acute hypoxia, and the role of this phenomenon will be clarified in the following report. The mRNA and protein expression levels of BPGM and the content of 2,3-DPG with hypoxia treatment were determined in vitro and in vivo. Furthermore, glycolysis was evaluated upon in hypoxic astrocytes with BPGM knockdown and in normoxic astrocytes with BPGM overexpression or 2,3-DPG treatment. To investigate the mechanism by which BPGM/2,3-DPG regulated glycolysis in hypoxic astrocytes, we detected the expression of HIF-1α, FIH-1 and TET2 with silencing or overexpression of BPGM and 2,3-DPG treatment. The expression of glycolytic genes and the capacity of lactate markedly increased with 6 h, 12 h, 24 h, 36 h and 48 h 1 % O₂ hypoxic treatment in astrocytes. The expression of BPGM was upregulated, and the production of 2,3-DPG was accelerated upon hypoxia. Moreover, when BPGM expression was knocked down, glycolysis was promoted in HEB cells. However, overexpression of BPGM and addition of 2,3-DPG to the cellular medium in normoxic cells could downregulate glycolytic genes. Furthermore, HIF-1α and TET2 exhibited higher expression levels and FIH-1 showed a lower expression level upon BPGM silencing, while these changes were reversed under BPGM overexpression and 2,3-DPG treatment. Our study revealed that the BPGM/2,3-DPG pathway presented a suppressive effect on glycolysis in hypoxic astrocytes by negatively regulating HIF-1α and TET2.

Aim: To investigate the molecular mechanisms underlying memory impairment induced by high‐altitude (HA) hypoxia, specifically focusing on the role of cold‐inducible RNA‐binding protein (CIRP) in regulating the AMPA receptor subunit GluR1 and its potential as a therapeutic target.Methods: A mouse model was exposed to 14 days of hypobaric hypoxia (HH), simulating conditions at an altitude of 6000 m. Behavioral tests were conducted to evaluate memory function. The expression, distribution, and interaction of CIRP with GluR1 in neuronal cells were analyzed. The binding of CIRP to GluR1 mRNA and its impact on GluR1 protein expression were examined. Additionally, the role of CIRP in GluR1 regulation was assessed using Cirp knockout mice. The efficacy of the Tat‐C16 peptide, which consists of the Tat sequence combined with the CIRP 110‐125 amino acid sequence, was also tested for its ability to mitigate HH‐induced memory decline.Results: CIRP was primarily localized in neurons, with its expression significantly reduced following HH exposure. This reduction was associated with decreased GluR1 protein expression on the cell membrane and increased localization in the cytoplasm. The interaction between CIRP and GluR1 was diminished under HH conditions, leading to reduced GluR1 stability on the cell membrane and increased cytoplasmic relocation. These changes resulted in a decreased number of synapses and dendritic spines, impairing learning and memory functions. Administration of the Tat‐C16 peptide effectively ameliorated these impairments by modulating GluR1 expression and distribution in HH‐exposed mice.Conclusion: CIRP plays a critical role in maintaining synaptic integrity under hypoxic conditions by regulating GluR1 expression and distribution. The Tat‐C16 peptide shows promise as a therapeutic strategy for alleviating cognitive decline associated with HA hypoxia.

The diagnosis and evaluation of the severity of acute mountain sickness (AMS) continue to be problematic due to a lack of consensus on the inclusion of symptoms in a scoring system. Recent investigations highlight the significance of gastrointestinal symptoms in identifying this condition. However, the specific gastrointestinal symptoms associated with AMS have not been thoroughly elucidated in previous studies, and the underlying risk factors remain inadequately comprehended. This study aimed to investigate the characteristics, trends, and risk factors related to gastrointestinal symptoms encountered during train travel to high altitude. A total of 69 passengers, specifically all with medical backgrounds, were surveyed 6 times over a period of 14 days. The daily incidence of abdominal discomfort was higher than non-gastrointestinal symptoms within 14 days. Gastrointestinal symptoms demonstrated a greater prevalence, longer duration, and increased risk compared to non-gastrointestinal symptoms, such as headaches. The symptoms of abdominal distension and bowel sound hyperaction were found to be prevalent and persistent among patients diagnosed with AMS, exhibiting a high incidence rate. Gender, age, body mass index (BMI), smoking habits, and alcohol consumption were identified as risk factors associated with the occurrence and duration of gastrointestinal symptoms. This study suggests that gastrointestinal symptoms are more common and persistent when traveling to the plateau by train. These symptoms should be taken into consideration in the further diagnosis and prevention of AMS. Therefore, this study provides a significant theoretical foundation for the prevention and treatment of AMS.