OBJECTIVE: Tibetan patients undergoing total knee arthroplasty (TKA) have greater fluctuations in perioperative haemoglobin levels and blood hypercoagulability. This study was to investigate whether ethnicity and altitude affect perioperative blood loss and the risk of complications after TKA.
METHODS: We retrospectively enrolled 1,116 patients undergoing TKA for knee osteoarthritis at our hospital between January 2016 and September 2021. We divided patients into four groups according to whether they were of Tibetan or Han ethnicity and whether they lived above or below 2500 m above sea level. Primary outcomes were total, intraoperative, and hidden blood losses, while secondary outcomes were complications and homologous transfusion. Factors associated with increased blood loss were analyzed by multivariate regression.
RESULTS: Total blood loss was higher among patients residing at high altitude compared with lower altitude, whether they were of Han (794.6 mL vs. 667.2 mL, P = 0.020) or Tibetan (904.4 mL vs. 663.8 mL, P < 0.001). Total blood loss was similar between the two ethnic groups at the same altitude. Altitude, but not Tibetan ethnicity, remained associated with increased blood loss after being analyzed by multivariate regression. Complications among the four groups were generally similar, although the frequency of calf muscular venous thrombosis was higher among Tibetan patients, while the frequency of blood transfusion was higher among Han subjects.
CONCLUSIONS: Our findings indicate that residence at high altitude, but not ethnicity, may contribute to increased total blood loss during TKA. Thrombotic complications were more frequent among Tibetan than Han patients.

UNASSIGNED: RESLES (Reversible splenial lesion syndrome) can be observed secondary to various diseases, and intramyelinic edema may play a crucial role in the pathogenesis of SCC (Splenium of the corpus callosum). Some studies have suggested that hypoxic-ischaemic encephalopathy may constitute a risk factor for SCC lesions. However, the potential impact of high-altitude environments on SCC, especially during chronic exposure, remain obscure.
UNASSIGNED: Our study included 19 patients who satisfied the diagnostic criteria of RESLES at high altitudes. Ten low-altitude patients with RESLES were included as controls. All participants received MRI (Magnetic resonance imaging) scans twice. Routine blood tests, liver, kidney and thyroid function, coagulation function, electrolytes and vitamins were detected during hospitalization and before discharge. In addition, the patients were followed up in May 2023.
UNASSIGNED: Hypoxic environments at high altitudes may increase the risk of RESLES. The two groups showed different clinical symptoms. High-altitude patients had significantly higher CRP levels than low-altitude patients. The lesion size in high-altitude patients showed a positive correlation with SaO2 levels. However, the patients at low altitudes had positive correlation trends between lesion size and several inflammatory markers (WBC, NEU and CRP). All patients had a benign prognosis that may not be affected by the use of prednisone acetate.
UNASSIGNED: Hypoxic environments at high altitudes may play a role in the aetiology of RESLES. Additionally, RESLES is a reversible disease and the administration of glucocorticoids may be dispensable for its treatment.

UNASSIGNED: Depressive symptoms have become a public health issue of common concern in countries all over the world, and have many negative impacts on university students\' study and life. Depressive symptoms are influenced by many factors, including sugar-sweetened beverages (SSBs) consumption and duration of physical activity. However, no study has been conducted on the association between sugar-sweetened beverage consumption, duration of physical exercise, and depressive symptoms among Tibetan university students at high altitudes.
UNASSIGNED: In this study, a self-assessment survey of SSBs consumption, duration of physical exercise, and depressive symptoms was conducted on 6,259 (2,745 boys, 43.86%) Tibetan university students aged 19-22 years in Lhasa and Ganzi areas, China, using stratified whole population sampling. The associations were also analyzed using one-way analysis of variance, binary logistic regression analysis, and ordered logistic regression analysis in the generalised linear model.
UNASSIGNED: The proportions of mild depression symptoms, moderate depression symptoms, and major depressive symptoms among Tibetan boys university students in high-altitude areas of China were 18.0, 22.9, and 1.5%, respectively; the proportions of girls students were 20.1, 21.9, and 1.5%, respectively, 1.5%, and the differences in the detection rates of depressive symptoms between sex were statistically significant (χ 2 value = 14.253, p < 0.01). Ordered logistic regression analyses showed that using duration of physical exercise >60 min/d and SSBs ≤1 times/week as the reference group, the duration of physical exercise <30 min/d and SSBs ≥5 times/week groups had the highest risk of developing depressive symptoms was the highest risk (OR = 6.98, 95% CI: 5.05-9.65; p < 0.001).
UNASSIGNED: This study confirmed that there was a positive association between SSBs consumption and depressive symptoms and a negative association between the duration of physical exercise and depressive symptoms among Tibetan university students at high altitudes in China. In the future, SSBs consumption should be effectively controlled and the duration of physical exercise should be increased to reduce the occurrence of depressive symptoms and promote the physical and mental health of Tibetan university students in high-altitude areas.

High-altitude acclimatization refers to the physiological adjustments and adaptation processes by which the human body gradually adapts to the hypoxic conditions of high altitudes after entering such environments. This study analyzed three mRNA expression profile datasets from the GEO database, focusing on 93 healthy residents from low altitudes (≤1400 m). Peripheral blood samples were collected for analysis on the third day after these individuals rapidly ascended to higher altitudes (3000-5300 m). The analysis identified significant differential expression in 382 genes, with 361 genes upregulated and 21 downregulated. Further, gene ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that the top-ranked enriched pathways are upregulated, involving blood gas transport, erythrocyte development and differentiation, and heme biosynthetic process. Network analysis highlighted ten key genes, namely, SLC4A1, FECH, EPB42, SNCA, GATA1, KLF1, GYPB, ALAS2, DMTN, and GYPA. Analysis revealed that two of these key genes, FECH and ALAS2, play a critical role in the heme biosynthetic process, which is pivotal in the development and maturation of red blood cells. These findings provide new insights into the key gene mechanisms of high-altitude acclimatization and identify potential biomarkers and targets for personalized acclimatization strategies.

UNASSIGNED: The study aimed to explore the risk factors for hyperuricemia (HUA) in the Naxi ethnic population residing in high-altitude areas of Yunnan, China, and assess the clinical value of the triglyceride/high-density lipoprotein cholesterol (TG/HDL-c) ratio as a diagnostic marker.
UNASSIGNED: In this cross-sectional study, clinical data were collected from the health checkup population in the People\'s Hospital of Yulong Naxi Autonomous County, Yunnan Province, from January 2021 to January 2023. Participants were divided into quartiles based on the TG/HDL-c ratio (Q1, Q2, Q3, and Q4) for group analysis using chi-square tests, t-tests, and rank sum tests. Logistic regression analysis and linear regression models were employed to further investigate the correlation between the prevalence of hyperuricemia and TG/HDL-c ratio in this high-altitude Naxi population.
UNASSIGNED: A total of 714 participants from the health checkup population were included in the study, of whom 61.5% were male participants and 38.5% were female participants, and the average age was 41.21 ± 11.69 years. The mean uric acid level was 388.51 ± 99.24. After correcting for confounding factors, TG/HDL-c, serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), red blood cells (RBCs), and hemoglobin (Hb) showed a positive correlation with blood uric acid. Further analysis involved categorizing the TG/HDL-c ratio from a continuous variable to a categorical variable using quartiles. The fully adjusted model showed results that were consistent with the trend observed in the continuous variable analysis when considering the TG/HDL-c ratio as a categorical variable. In addition, in all unadjusted and adjusted models, the serum uric acid (SUA) levels in the high TG/HDL-c ratio group were significantly higher than those in the low TG/HDL-c ratio group (trend p < 0.001). Further linear relationship analysis indicated that after adjusting for covariates, there was an approximate linear relationship between the TG/HDL-c and SUA levels, with a coefficient (β) of 5.421.
UNASSIGNED: The prevalence of hyperuricemia is greater in high-altitude areas of Yunnan, showing a nearly linear positive correlation with the TG/HDL-c ratio. Monitoring TG/HDL-c levels may benefit patients with hyperuricemia.

BACKGROUND: The incidence of gallstones is high in Qinghai Province. However, the molecular mechanisms underlying the development of gallstones remain unclear.
METHODS: In this study, we collected urine samples from 30 patients with gallstones and 30 healthy controls. The urine samples were analysed using multi-omics platforms. Proteomics analysis was conducted using data-independent acquisition, whereas metabolomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS).
RESULTS: Among the patients with gallstones, we identified 49 down-regulated and 185 up-regulated differentially expressed proteins as well as 195 up-regulated and 189 down-regulated differentially expressed metabolites. Six pathways were significantly enriched: glycosaminoglycan degradation, arginine and proline metabolism, histidine metabolism, pantothenate and coenzyme A biosynthesis, drug metabolism-other enzymes, and the pentose phosphate pathway. Notably, 10 differentially expressed proteins and metabolites showed excellent predictive performance and were selected as potential biomarkers.
CONCLUSIONS: The findings of our metabolomics and proteomics analyses provide new insights into novel biomarkers for patients with cholelithiasis in high-altitude areas.

Sheep were domesticated in the Fertile Crescent and then spread globally, where they have been encountering various environmental conditions. The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years. To explore genomic variants associated with high-altitude adaptation in Tibetan sheep, we analyzed Illumina short-reads of 994 whole genomes representing ∼ 60 sheep breeds/populations at varied altitudes, PacBio High fidelity (HiFi) reads of 13 breeds, and 96 transcriptomes from 12 sheep organs. Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation. Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associated β-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds. The haplotype A carried two homologous gene clusters: (1) HBE1, HBE2, HBB-like, and HBBC, and (2) HBE1-like, HBE2-like, HBB-like, and HBB; while the haplotype B lacked the first cluster. The high-altitude sheep showed highly frequent or nearly fixed haplotype A, while the low-altitude sheep dominated by haplotype B. We further demonstrated that sheep with haplotype A had an increased hemoglobin-O2 affinity compared with those carrying haplotype B. Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep. Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.

Wang, Bowen, Mengjia Peng,, Liheng Jiang,, Fei Fang,, Juan Wang,, Yan Li,, Ruichen Zhao,, and Yuliang Wang,. A Rare Case of High-Altitude Polycythemia Complicated by Spontaneous Splenic Rupture. High Alt Med Biol. 25:247-250, 2024.-High-altitude polycythemia, a condition characterized by an increase in red blood cellRBC mass, can occur after prolonged exposure to high altitudes. While several studies have explored the complications associated with high-altitude polycythemia, there is currently no literature available on spontaneous spleen rupture caused by high-altitude polycythemia. Here, we reported a case of acute abdominal pain and hemodynamic instability in a 36-year-old male who had been residing at high altitude for 6 years, without any recent history of trauma. Computed tomography imaging revealed significant fluid accumulation in the abdomen, and a tear of the splenic capsule was identified during the following laparotomy. Subsequent evaluations confirmed the presence of polycythemia secondary to prolonged high-altitude exposure as the underlying etiology. This case served as an important reminder that high-altitude polycythemia could lead to serious complications, such as spontaneous spleen rupture. Clinicians should be aware of this potential complication and consider it in the differential diagnosis of patients presenting with abdominal pain and hemodynamic instability in this population.

BACKGROUND: Exposure to a high-altitude environment is a risk factor for cerebral venous thrombosis (CVT) probably due to hypercoagulability. The study aims to explore the unique characteristics of CVT patients in high-altitude areas of China by comparing them with those in plain areas.
METHODS: We retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People\'s Hospital (altitude 3650 m) and Peking Union Medical College Hospital (altitude 43.5 m) between January 2015 and December 2023. Patients from the plateau and the plain were considered two independent groups in this study. The risk factors, clinical and radiological presentations, treatment, and outcomes were analyzed and compared between the two groups.
RESULTS: A total of 169 patients with CVT were included in the study, 48 patients from plateau and 121 patients from plain. The median age was 27 and 34 years old, and women accounted for 66.7% and 54.5% respectively. Headache (91.7% vs. 71.1%, P = 0.004), altered consciousness (31.3% vs. 16.5%, P = 0.033), hemorrhage (41.7% vs. 19.0%, P = 0.002), and venous infarction (50.0% vs. 25.6%, P = 0.002) on imaging were more common in patients from plateau than those from plain. Pregnancy or puerperium was significantly more common in highland patients (25% vs. 5.8%, P < 0.001). The levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), fibrinogen (3.7 vs. 3.0 g/L, P < 0.001), hemoglobin (157 vs. 129 g/L, P = 0.01), white blood cells (9.6 vs. 7.5*1012/L, P < 0.001) and highly sensitive C-reactive protein (20.2 vs. 3.2 mg/L, P = 0.005) were remarkably higher in highland patients. The percentage of receiving anticoagulant therapy was lower in high-altitude patients (70.8% vs. 93.4%, P < 0.001). Favorable outcome at follow-up was observed in 81.4% of highland patients and 90.7% of lowland patients, with a median follow-up time of 330 days and 703 days respectively.
CONCLUSIONS: The more severe clinical and imaging manifestations along with prominent inflammatory and hypercoagulable states were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at high altitude. Pregnancy or puerperium were more common in highland patients. The overall prognosis of CVT patients from both groups were favorable.

The adverse impacts of chronic hypoxia on maternal and infant health at high altitudes warrant significant attention. However, effective protective measures against the resultant growth restrictions and neurodevelopmental disorders in infants and young children are still lacking. This study investigated the neurodevelopment of mice offspring under hypoxic conditions by exposing pregnant mice to a hypobaric oxygen chamber that simulated the hypobaric hypoxia at an altitude of 4000 m until 28 days after delivery. Our findings suggested that prolonged exposure to hypoxia might result in emotional abnormalities and social disorders in offspring. The significant reduction in astrogliogenesis was a characteristic feature associated with neurodevelopmental disorders induced by hypoxia. Further studies demonstrated that cold-induced RNA-binding protein (CIRBP) was a key transcriptional regulator in astrogliogenesis, which downregulated astrocytic differentiation under hypoxia through its crosstalk with the NFIA. Our study emphasized the crucial role of CIRBP in regulating astrogliogenesis and highlighted its potential as a promising target for therapeutic interventions in neurodevelopmental disorders associated with hypoxia.