High altitude medicine & biology最新文献

{"title":"High-Altitude Pulmonary Edema in Children in Mexico City: A Case Series.","authors":"Alejandro Ferreiro Marín, María Paula Ferreiro Soria, Karla Sánchez Olivera, Aranza Suárez Ortega, Luis Martín Garrido García","doi":"10.1177/15578682261500306","DOIUrl":"https://doi.org/10.1177/15578682261500306","url":null,"abstract":"<p><p>Marín, Alejandro Ferreiro, María Paula Ferreiro Soria, Karla Sánchez Olivera, Aranza Suárez Ortega, and Luis Martín Garrido García. High-altitude pulmonary edema in children in Mexico City: A case series. <i>High Alt Med Biol.</i> 00:00-00, 2026.-High-altitude pulmonary edema (HAPE) is a potentially life-threatening form of noncardiogenic pulmonary edema caused by hypobaric hypoxia. Although well characterized in adults, pediatric cases remain underrecognized and are frequently mistaken for pneumonia.We describe four pediatric patients aged 7-12 years diagnosed with HAPE at a Private Tertiary Referral Medical Center in Mexico City. One patient developed classic HAPE after ascent from low altitude, and three patients developed reentry HAPE after returning to high altitude following temporary stays near sea level.All patients presented with hypoxemia (SpO₂ 77%-93%), respiratory symptoms, bilateral pulmonary infiltrates, absence of fever, and low inflammatory markers. Echocardiography demonstrated elevated or borderline elevated pulmonary artery pressures without structural heart disease. Supplemental oxygen resulted in rapid clinical improvement in all cases. Hospital stay ranged from 2 to 4 days, and none required mechanical ventilation. One patient experienced recurrence shortly after discharge.HAPE should be considered in children presenting with acute hypoxemic respiratory illness after recent ascent to high altitude. The combination of hypoxemia, bilateral infiltrates, low inflammatory markers, and rapid response to oxygen therapy may help distinguish HAPE from infectious pneumonia and facilitate timely treatment.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"15578682261500306"},"PeriodicalIF":1.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Etiological and Clinical Patterns of Acute Mesenteric Ischemia at High Altitude: A Retrospective Comparative Study.","authors":"Yonghao Chen, Biao Chen, Daiyu Yang, Shuai Li, Hemiao Xu, Zhengyang Fan, Haifeng Xu, Zhijuan Liu, Dong Wu","doi":"10.1177/15578682261497522","DOIUrl":"https://doi.org/10.1177/15578682261497522","url":null,"abstract":"<p><p>Chen, Chen, Yang, Li, Xu, Fan, Xu, Zhijuan Liu, and Dong Wu. Distinct etiological and clinical patterns of acute mesenteric ischemia at high altitude: a retrospective comparative study. <i>High Alt Med Biol.</i> 00:00-00, 2026.</p><p><strong>Background: </strong>Acute mesenteric ischemia (AMI) is a life-threatening abdominal emergency, yet evidence regarding its etiology and clinical outcomes in high-altitude populations remains limited. This study aimed to compare the etiology, clinical characteristics, and outcomes of AMI between high- and low-altitude populations in China.</p><p><strong>Methods: </strong>We conducted a retrospective comparative study at two tertiary referral centers in China: People's Hospital of the Xizang Autonomous Region (PHOXAR; 3,700 m) and Peking Union Medical College Hospital (PUMCH; <100 m). Mesenteric venous thrombosis (MVT) comparisons were restricted to the overlapping period of 2020-2024.</p><p><strong>Results: </strong>Among 186 patients in the high-altitude cohort and 549 in the low-altitude cohort, MVT was more frequent at high altitude (84.9% vs. 61.2%, <i>p</i> < 0.001). 158 high-altitude and 120 low-altitude patients with MVT were compared. Cirrhosis-related (29.1% vs. 11.7%) and erythrocytosis-related MVT (27.2% vs. 1.7%) were more common in the high-altitude cohort, whereas autoimmune disease-related MVT (0.6% vs. 11.7%) and thrombophilia (0 vs. 16.7%) were more frequent in the low-altitude cohort. High-altitude patients had higher hemoglobin/hematocrit, bilirubin, and fibrinogen levels and a higher mean onset-to-admission time (95.4 vs. 30.2 days). They underwent surgery less frequently (29.7% vs. 80.0%, <i>p</i> < 0.001) and had higher in-hospital mortality (26.6% vs. 11.7%, <i>p</i> = 0.004). Mortality was not significantly different among patients admitted within 2 days (31.6% vs. 8.3%, <i>p</i> = 0.111) but remained higher among those admitted after 2 days (25.9% vs. 12.5%, <i>p</i> = 0.012). Male sex, older age, alcohol consumption, smoking, and higher hematocrit, bilirubin, and fibrinogen were independently associated with the high-altitude MVT phenotype.</p><p><strong>Conclusions: </strong>AMI in the high-altitude population was characterized by a marked predominance of MVT, with distinct etiological and clinical profiles and poorer outcomes. These findings highlight the importance of early recognition, timely referral, and improved access to appropriate treatment for AMI in high-altitude settings.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"15578682261497522"},"PeriodicalIF":1.3,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter:</i> The High-Altitude Exposome: A New Framework for Health Research.","authors":"Diana E Alcantara-Zapata","doi":"10.1177/15578682261497521","DOIUrl":"https://doi.org/10.1177/15578682261497521","url":null,"abstract":"","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"15578682261497521"},"PeriodicalIF":1.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Training Load and Performance Characteristics Across Two Consecutive Winter Altitude-Training Cycles in Women's Quadruple Sculls Olympic Champions Preparing for the Beijing Olympics.","authors":"Yangyang Zhang, Yuan Li, Zhijun Meng, Binghong Gao","doi":"10.1177/15578682261493180","DOIUrl":"https://doi.org/10.1177/15578682261493180","url":null,"abstract":"<p><p>Zhang, Yangyang, Yuan Li, Zhijun Meng, and Binghong Gao. Training load and performance characteristics across two consecutive winter altitude-training cycles in women's quadruple sculls olympic champions preparing for the Beijing Olympics. <i>High Alt Med Biol</i> 00:00-00, 2026.</p><p><strong>Background: </strong>Longitudinal evidence from Olympic-level rowing squads across consecutive winter preparations is scarce.</p><p><strong>Methods: </strong>This retrospective longitudinal case series described weekly training load and pre-to-post ergometer performance in a five-rower preparation squad during linked 2006-2007 and 2007-2008 winter altitude-training cycles at ∼2,300 m; four athletes later formed the Beijing Olympic champion crew.</p><p><strong>Results: </strong>Intensity-coded volume totaled 3,911.4 and 4,127.4 km. The second cycle contained more ergometer work and a larger share of Levels V-VI rowing. Mean 2,000-m time changed by -5.98 seconds (95% confidence interval [CI]: -16.24 to 4.28; <i>p</i> = 0.181) and -6.00 seconds (95% CI: -10.71 to -1.29; <i>p</i> = 0.024), respectively. The between-cycle change-score estimate was 0.02 seconds (95% CI: -12.31 to 12.33; <i>p</i> = 0.997). The two lactate-test protocols were interpreted separately. All five athletes improved in the available first-cycle 6,000-m comparison.</p><p><strong>Conclusions: </strong>Across two Olympic-preparation winters, distinct training-load organizations were each accompanied by favorable sport-specific performance trajectories. These rare Olympic-champion records provide an applied benchmark for describing how volume, modality, and intensity were reorganized and reinforce the value of athlete-specific monitoring without prescribing a universal training model.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"15578682261493180"},"PeriodicalIF":1.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPARα Activation Attenuates Right Ventricular Hypertrophy by Regulating Myocardial Glucose and Lipid Metabolism in High-Altitude Pulmonary Hypertension <i>In Vivo</i> and <i>In Vitro</i>.","authors":"Xiaoying Zhang, Jiajia Wu, Yuchan Zhang, Yuquan Xie, Qi Si, Shadi Li, Yiwei Han","doi":"10.1177/15578682261490525","DOIUrl":"https://doi.org/10.1177/15578682261490525","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Zhang, Xiaoying, Jiajia Wu, Yuchan Zhang, Yuquan Xie, Qi Si, Shadi Li, and Yiwei Han. PPARα activation attenuates right ventricular hypertrophy by regulating myocardial glucose and lipid metabolism in high-altitude pulmonary hypertension &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt;. &lt;i&gt;High Alt Med Biol.&lt;/i&gt; 00:00-00, 2026.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Right ventricular hypertrophy (RVH) and cardiac function are key prognostic determinants in patients with high-altitude pulmonary hypertension. Meanwhile, their initiation and progression are driven by disturbances in glucose and lipid metabolism in cardiomyocytes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study established an SU5416-associated hypobaric hypoxia-induced RVH (H-RVH) rat model and a CoCl&lt;sub&gt;2&lt;/sub&gt;-induced hypoxic cardiomyocyte model to explore glucose and lipid metabolism alterations and mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The metabolomic cluster analysis of metabolites primarily focused on lipid metabolism, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathways, including glycolysis/gluconeogenesis, glycerophospholipid metabolism, and the peroxisome proliferator-activated receptor (PPAR) signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with the control group, glucose transporter-4 (GLUT-4) and pyruvate dehydrogenase (PDH) kinase were increased by 320% and 220% in H-RVH rats, respectively (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), whereas PDH and citrate synthase (CS) were decreased by 39% and 58%, respectively (&lt;i&gt;p&lt;/i&gt; &lt; 0.05), collectively indicating a shift toward glycolysis and away from glucose oxidation. Seahorse Extracellular Flux (XF) assay revealed that basal glycolysis and compensatory glycolytic capacity were significantly elevated in the CoCl&lt;sub&gt;2&lt;/sub&gt;-induced hypoxic cardiomyocyte model compared with the control group (288.5 ± 9.82 vs. 344.1 ± 10.24, 335.9 ± 11.58 vs. 385.7 ± 14.74, &lt;i&gt;p&lt;/i&gt; &lt; 0.05). The expression levels of PPARα and carnitine palmitoyltransferase 1α (CPT-1α) in the H-RVH group were 48% and 56% lower than those in the control group, respectively (&lt;i&gt;p&lt;/i&gt; &lt; 0.05); acetyl-CoA and adenosine triphosphate (ATP) were also reduced (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Fenofibrate mitigated CoCl&lt;sub&gt;2&lt;/sub&gt;-induced hypoxic damage through 1.6-fold activation of PPARα. Cardiac-specific PPARα overexpression via an adeno-associated virus (AAV9) effectively attenuated RVH, as evidenced by the reduction in Fulton's index (0.37 ± 0.09 vs. 0.46 ± 0.02, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), right ventricular anterior wall diastolic (RVAWd) (0.64 ± 0.04 vs. 0.93 ± 0.02, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and RVAWs (0.68 ± 0.05 vs. 0.97 ± 0.02, &lt;i&gt;p&lt;/i&gt; &lt; 0.01). In contrast, PPARα knockdown did not significantly alter the Fulton index but markedly increased both RVAWd (1.00 ± 0.01 vs. 0.77 ± 0.03, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and RVAWs (1.00 ± 0.02 vs. 0.70 ± 0.05, &lt;i&gt;p&lt;/i&gt; &lt; 0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In this study, our findings demonstrate that PPARα exerts a protective effect against RVH, at least in part, b","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"15578682261490525"},"PeriodicalIF":1.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>A Response to the Letter to the Editor:</i> The Development of Acute Mountain Sickness Does Not Depend Solely on the Absence of the m.12320A>G Variant.","authors":"Cuiping Pan, Zongbin Li","doi":"10.1177/15578682261489789","DOIUrl":"https://doi.org/10.1177/15578682261489789","url":null,"abstract":"","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"15578682261489789"},"PeriodicalIF":1.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of Color Vision in School Children in High Altitude, Leh, India.","authors":"Sagarika Patyal, Jasdeep Singh, Kanika Bhardwaj, Uday Yanamandra","doi":"10.1177/15578682261489792","DOIUrl":"https://doi.org/10.1177/15578682261489792","url":null,"abstract":"<p><p>Patyal, Sagarika, Jasdeep Singh, Kanika Bhardwaj, and Uday Yanamandra. Determination of color vision in school children in high altitude, Leh, India. <i>High Alt Med Biol.</i> 00:00-00, 2026.</p><p><strong>Introduction: </strong>Color vision deficiency (CVD) is a heritable condition predominantly affecting males due to its X-linked recessive inheritance. High altitude may exacerbate color discrimination impairment through hypobaric hypoxia-mediated depression of retinal function, particularly affecting short-wavelength cone pathways. Population-based data on CVD from high-altitude Indian communities are absent from the literature.</p><p><strong>Materials and methods: </strong>A cross-sectional study was conducted at Lamdon School, Leh, Ladakh, India (11,400 ft/3,474 m above sea level). A total of 505 schoolchildren (204 boys; 301 girls) aged 11-18 years underwent a structured ophthalmical examination and color vision testing using the 38-plate Ishihara pseudoisochromatic plate test under standardized conditions.</p><p><strong>Results: </strong>CVD was detected in 53 of 505 children (10.50%): 22 boys (10.78%) and 31 girls (10.30%). No statistically significant sex difference in CVD prevalence was detected (Fisher's exact test, <i>p</i> = 0.883). Severity analysis revealed a significant sex interaction: girls predominated in mild (21/33) and moderate (9/12) CVD categories, while boys constituted 7 of 8 severely color-deficient children (≥5 plate errors). CVD prevalence rose with age, peaking at 20.7% in 18-year-olds. Plates 9 and 17 generated the highest error frequencies; plate 9 elicited errors exclusively in boys, and plate 17 elicited errors exclusively in girls. Plate-specific misidentification patterns deviated from standard Ishihara predictions in both sexes.</p><p><strong>Conclusions: </strong>The overall CVD prevalence in this high-altitude Ladakhi population substantially exceeds rates reported at sea level in India and most global populations, mirroring the altitude-related pattern documented in Nepal. The severity paradox, girls dominating mild CVD while boys dominate severe CVD, suggests that carrier females heterozygous for CVD-associated alleles may be expressing phenotypically detectable color discrimination impairment at altitude, possibly through hypoxia-mediated amplification of their marginal trichromatic capacity.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"15578682261489792"},"PeriodicalIF":1.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148967982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter:</i> High Altitude Medical Kit.","authors":"James F Bridger, Jeremy S Windsor","doi":"10.1177/15578682261429336","DOIUrl":"10.1177/15578682261429336","url":null,"abstract":"","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"203-204"},"PeriodicalIF":1.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute High-Altitude Exposure Increases Transcription of Tricarboxylic Acid Cycle Enzymes in Human Duodenal Biopsies.","authors":"Patrick-Pascal Strunz, Raphael N Vuille-Dit-Bille, Heiko Fruehauf, Mark Fox, Andreas Geier, Marco Maggiorini, Max Gassmann, Thomas A Lutz, Oliver Goetze","doi":"10.1177/15578682251374980","DOIUrl":"10.1177/15578682251374980","url":null,"abstract":"<p><p>Strunz, Patrick-Pascal, Raphael N. Vuille-dit-Bille, Heiko Fruehauf, Mark Fox, Andreas Geier, Marco Maggiorini, Max Gassmann, Thomas A. Lutz, and Oliver Goetze. Acute high-altitude exposure increases transcription of tricarboxylic acid cycle enzymes in human duodenal biopsies. <i>High Alt Med Biol</i>. 27:184-188, 2026.</p><p><strong>Background: </strong>A recent study of our group quantifying ¹³C-octanoate metabolism in HA (Capanna Margherita [MG]/4,559 m) showed that acute HA exposure might lead to an increase of the lipolytic and CO₂-producing pathways.</p><p><strong>Objective: </strong>To further test this hypothesis, we investigated intestinal biopsies from the same participants from simultaneously performed endoscopy studies for changes of mRNA-expression levels of the beta-oxidation enzymes and the decarboxylating tricarboxylic acid cycle (TCA) enzymes.</p><p><strong>Methods: </strong>Duodenal biopsies of 16 subjects exposed to HA were sampled via gastro-duodenoscopy at Zurich (baseline ZH, 490 m), on day 2 (MG2) and on day 4 at HA (MG4). After mRNA extraction, quantitative real-time polymerase chain reaction was performed to assess mRNAs expression of TCA cycle enzymes as well as beta-oxidation enzymes.</p><p><strong>Results: </strong>Aconitase mRNA levels increased early (MG2 vs. ZH, <i>p</i> < 0.05) and were still higher at day 4 compared with ZH (MG4 vs. ZH, <i>p</i> < 0.05). Isocitrate dehydrogenase (DH) levels increased with time spent at 4,559 m (MG4 vs. ZH, <i>p</i> < 0.01). The remaining TCA cycle and beta-oxidation enzymes investigated tended to higher values at HA but without reaching significance.</p><p><strong>Conclusion: </strong>We conclude that acute exposure to HA leads to increased transcription of aconitase and isocitrate DH in the duodenal mucosa due to hypobaric hypoxia exposure.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"184-188"},"PeriodicalIF":1.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144951957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Adaptation to Tibetan High Altitude and Hepatocellular Cancer Risk: Integrative Bidirectional Mendelian Randomization and Single-Cell RNA Sequencing Analysis.","authors":"Nimadeji, Yanna Cai, Na Gao","doi":"10.1177/15578682251409078","DOIUrl":"10.1177/15578682251409078","url":null,"abstract":"<p><p>Nimadeji, Yanna Cai, and Na Gao. Genetic adaptation to Tibetan high altitudes and hepatocellular cancer risk: integrative bidirectional Mendelian randomization and single-cell RNA sequencing analysis. <i>High Alt Med Biol.</i> 27:159-167, 2026.</p><p><strong>Background: </strong>The unique genetic adaptations of Tibetans to high-altitude environments may influence disease susceptibility, including hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>We employed bidirectional two-sample Mendelian randomization (MR) using genome-wide association study summary statistics: high-altitude adaptation (HAA) data from Tibetan/non-Tibetan East Asians (<i>n</i> = 10,295) and HCC data from BioBank Japan (1,866 cases/195,745 controls). Instrumental variables were selected via genome-wide significance (<i>p</i> < 5 × 10^-8), with inverse variance-weighted random-effects models as primary analysis. MR-Egger regression analysis and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global analysis were used to evaluate the pleiotropic effect. Single-cell RNA sequencing from the Hepatocellular Carcinoma Database identified HAA-related differentially expressed genes (DEGs) in HCC tissues, followed by functional enrichment analysis.</p><p><strong>Results: </strong>MR results demonstrated HAA as a causal risk factor for HCC (odds ratio = 2.15 × 10², 95% confidence interval = 1.57-2.96 × 10⁴, <i>p</i> = 0.032), with no reverse causality. Single-cell analysis revealed 23 HAA-associated DEGs in HCC, enriched in immune regulation, DNA metabolism, and cell growth pathways. Notably, genes such as <i>EPAS1</i> and <i>GCH1</i>; Guanosine triphosphate, GTP, previously linked to Tibetan HAA, were found to be differentially expressed in HCC tissues.</p><p><strong>Conclusion: </strong>This study provides statistical and genetic evidence that HAA is a causal risk factor for HCC in Tibetans. The identification of HAA-related genes in HCC tissues offers new insights for targeted prevention and treatment strategies in Tibetan populations.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":"159-167"},"PeriodicalIF":1.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}