Altitude-induced hypoxemia impairs exercise performance and cognition. Interestingly, ketone ester (KE) ingestion may attenuate hypoxemia, which likely explains the observation that KE impairs high-intensity exercise performance in normoxia but not in hypoxia. Moreover, KE was reported to attenuate cognitive decline at extreme altitudes (∼6,100 m). Given that hypoxemia is unaffected by KE in milder conditions, the impact of KE on cognition and performance in the absence of elevated oxygenation remains unknown. As KE may increase postexercise circulating [erythropoietin] ([EPO]) at sea level, we also assessed if KE might augment the blood [EPO] response after hypoxic exercise. In a double-blind, cross-over design, 13 healthy, male participants completed two 5.5-h sessions at 4,000-m simulated altitude while receiving either KE or placebo (CON). Throughout a graded exercise test (EXMAX) after 1.5 h, and a submaximal exercise bout (EXSUBMAX) after 3 h, blood and tissue oxygenation, ventilatory parameters, and acid-base balance were evaluated. Other measurements included cognitive function and blood [EPO]. KE reduced power output achieved during EXMAX by 3.6%, whereas blood and cerebral oxygenation were similar. KE ingestion lowered blood pH, [[Formula: see text]], pCO2, and [glucose], but did not impact cognitive function. In both KE and CON, circulating [EPO] increased by ∼56% after 5 h. These results indicate that KE ingestion impairs high-intensity exercise performance, at least if not compensated by elevated oxygenation. A progressively increasing oxygenation upon KE was unable to protect against hypoxia-induced cognitive declines and potentially counteracted a KE-induced augmentation of circulating [EPO].NEW & NOTEWORTHY This study is the first to show that KE ingestion impairs exercise performance in hypoxia, at least when KE does not alleviate hypoxemia. Despite a subsequent, progressive increase in oxygenation upon KE after 3-4 h, this does not protect against hypoxia-induced cognitive declines. Although studies in normoxia show potential of KE to increase blood [erythropoietin], we identified that KE ingestion fails to augment the increase in blood [erythropoietin] through hypoxic exposure and exercise.

This study aimed to evaluate the applicability of existing 6MWT reference equations to healthy children and adolescents living in a high-altitude city.

Healthy children aged 5 to 15 years attending two non-randomly selected schools in Bogotá were invited to participate in the study. All participants performed the 6MWT according to the European Respiratory Society/American Thoracic Society technical standards. To identify the model or set of 6MWT equations that best predicted individually measured 6MWT values in our population, we identified the narrowest limits of agreement (LOA) (mean difference between measured and predicted values ± 1.96 SD) after constructing Bland-Altman plots. We performed separate analyzes based on sex and onset of puberty, which was assumed to occur at 12 years of age for girls and 13 years of age for boys.

105 children and adolescents (61 girls, 58.1%) with a mean age of 10.04 years (±2.21), ranging from 6 to 15 years, were evaluated. We determined that equations derived from two different studies conducted in Brazil, de Assis, and Oliveira 6MWT equations provided the narrowest LOA in the Bland-Altman plots for the individually-measured 6MWT values for all study participants, except for the older female participants who obtained narrower LOA with the Ulrich equations.

For the mean walked distance of the 6MWT, we have provided information on the 6MWT predictive equations that may be most appropriate for use in healthy children living in Bogota, Colombia, a city at 2640 m altitude.

This study aimed to quantify the effect of two consecutive prolonged, intermittent exposures to high and very high altitudes on oxygen saturation (SpO2) and acute mountain sickness (AMS). For this, healthy lowlanders (N = 21), aged 18-30 years, underwent two 7-day sojourns at the ALMA observatory, Chile (6 h/day at 5050 m, 18 h/day at 2900 m), separated by 1-week at 520 m. SpO2 (pulse oximetry) and AMS severity (AMSc, Environmental Symptom Questionnaire cerebral score) diagnosing AMS (AMSc ≥ 0.7) were assessed daily at both altitudes. The study was registered at www.ClinicalTrials.gov: NCT02730143. SpO2 at 2900 m and 5050 m on arrival was mean ± SD 93.6 ± 0.5% and 79.9 ± 1.0% (P < 0.05 between altitudes), whereas the AMSc scores were 0.43 ± 0.08 and 0.97 ± 0.11 (P < 0.05 between altitudes), respectively. At 2900 m during a 7-day intermittent hypoxic exposure, SpO2 increased by a mean (95% CI) 0.3 %/day (0.1;0.4) and by 0.9 %/day (0.4;1.3) at 5050 m. Similarly, AMSc decreased by 0.05 points/day (0.01;0.08) at 2900 m and by 0.16 points/day (0.11;0.21) at 5050 m. During the second sojourn (vs. 1st sojourn), day 1, SpO2 at 2900 m was unchanged but higher at 5050 m by 2.9% (0.6;5.3). AMSc was lower at 2900 m and 5050 m by 0.37 (0.16;0.59) and 0.37 (0.11;0.63) (P < 0.05 both comparisons vs 1st sojourn), respectively. Acclimatization with the 2nd sojourn increased SpO2 at 2900 m by 0.3%/day (0.1;0.4) and 5050 m by 0.5%/day (0.1;0.8). AMSc remained unchanged with acclimatization at 2900 m but decreased at 5050 m by 0.08 points/day (0.04;0.11). In conclusion, in healthy lowlanders, a 7-day intermittent hypobaric hypoxic exposure improved SpO2 and AMS severity at 2900 m, with larger improvements at 5050 m. During a second identical sojourn, initial AMS severity was reduced despite comparable SpO2 at 2900 m compared to the 1st sojourn. No further acclimatization effects were observed in SpO2 but in AMS symptoms at 2900 m. In contrast, re-exposure to 5050 m showed higher initial SpO2 and lower AMSc values with further improvement with intermittent re-exposures. These findings highlight altitude-dependent acclimatization patterns and confirm pre-conditioning's effectiveness in preventing AMS.

Data on the oral health status in the Qinghai-Tibetan Plateau are limited. This study aimed to investigate the dental caries status and identify associated risk factors among 8- to 12-year-old children in Gannan, a Tibetan Autonomous Prefecture in Northwest China.

The study population was recruited using a multistage stratified random sampling procedure. Caries status was assessed by clinical oral examination and indicated by the decayed, missing, and filled teeth (DMFT/dmft) index. Information on sociodemographic characteristics, oral hygiene behaviours, and dietary habits was collected using a comprehensive structured questionnaire. Statistical analyses, including the chi-square test and a two-level logistic regression model, were conducted to examine the risk factors associated with dental caries.

A total of 1024 Tibetan children were examined, revealing a dental caries prevalence rate of 89.55%, with a mean DMFT/dmft index of 4.25 ± 3.27. The two-level logistic regression model showed that initiating tooth brushing at four to 5 years old (OR = 2.295, 95% CI 1.053-5.002) and frequent dessert and candy intake (OR = 2.655, 95% CI 1.216-5.794) were risk factors for dental caries. Conversely, being 11 years (OR = 0.399, 95% CI 0.177-0.904) or 12 years old (OR = 0.396, 95% CI 0.163-0.961) and if the father's education level was high school or above (OR = 0.311, 95% CI 0.098-0.986) were indicated to be protective factors against dental caries.

The prevalence of dental caries was high in Tibetan children aged 8 to 12year-old in Gannan. Therefore, it is imperative to prioritize comprehensive home- and school-based interventions to improve the oral health of this population.

Acute High Altitude Illness (AHAI) includes conditions such as Acute Mountain Sickness (AMS), High Altitude Cerebral Edema (HACE), and High Altitude Pulmonary Edema (HAPE), which result from rapid ascent to altitudes exceeding 2,500 m. Although interest in AHAI research has been growing, a systematic and comprehensive analysis of global research trends remains lacking.

A total of 3,214 articles and reviews published from 1937 to 2024 were retrieved from the Web of Science Core Collection. Bibliometric tools, including CiteSpace and VOSviewer, were applied to thoroughly assess publication trends, collaborative networks among authors, institutional contributions, and keyword co-occurrence patterns. The dataset represents the contributions of over 11,758 authors across 86 countries and 3,378 institutions, reflecting the significant growth of this research domain.

Our findings highlight the increasing scholarly attention to AHAI research, with the United States leading in publication numbers. Emerging research themes include cellular activation, oxidative stress, risk factors, and hypobaric hypoxia. This is the first systematic bibliometric review of AHAI literature, offering a detailed roadmap of research hotspots, potential collaborations, and key future directions. These findings provide a valuable reference for researchers aiming to explore gaps and build on the existing knowledge in high-altitude medicine.

High-altitude cerebral edema (HACE) is a disorder caused by low pressure and hypoxia at high altitudes. Nevertheless, as of now, there is still a scarcity of safe and effective prevention and treatment methods. The active component of Ligusticum Chuanxiong, namely Ligustrazine hydrochloride (LH), has shown potential in the prevention and treatment of HACE due to its anti-inflammatory, antioxidant, and neuroprotective effects in nervous system disorders. Consequently, the potential protective effect of LH on HACE and its mechanism still need to be further explored. Prior to modeling, 90 male Sprague-Dawley rats were pretreated with different doses of drugs, including LH (100 mg/kg and 50 mg/kg), dexamethasone (4 mg/kg), and ML385 (30 mg/kg). Subsequently, the pretreated rats were placed in a low-pressure anoxic chamber simulating a plateau environment to establish the rat HACE model. The effects and mechanisms of LH on HACE rats were further elucidated through determination of brain water content, HE staining, ELISA, immunofluorescence, molecular docking, molecular dynamics simulation, western blot, and other techniques. The results showed, first of all, that LH pretreatment can effectively reduce brain water content; down-regulate the expression of AQP4, HIF-1α, and VEGF proteins; and alleviate damage to brain tissue and nerve cells. Secondly, compared with the HACE group, LH pretreatment can significantly reduce MDA levels and increase GSH and SOD levels. Additionally, LH decreased the levels of inflammatory factors IL-1β, IL-6, and TNF-α; reduced total iron content in brain tissue; increased the expression of ferroptosis-related proteins such as SLC7A11, GPX4, and FTH1; and alleviated ferroptosis occurrence. Molecular docking and molecular dynamics simulations show that LH has a strong binding affinity for NRF2 signaling. Western blot analysis further confirmed that LH promotes the translocation of NRF2 from the cytoplasm to the nucleus and activates the NRF2 signaling pathway to exert an antioxidant effect. The NRF2 inhibitor ML385 can reverse the anti-oxidative stress effect of LH and its protective effect on HACE rat brain tissue. In summary, LH may have a protective effect on HACE rats by activating the NRF2 signaling pathway, inhibiting ferroptosis, and resisting oxidative stress.

Oxygen is essential for human life, yet a growing body of preclinical research is demonstrating that chronic continuous hypoxia can be beneficial in models of mitochondrial disease, autoimmunity, ischemia, and aging. This research is revealing exciting new and unexpected facets of oxygen biology, but translating these findings to patients poses major challenges, because hypoxia can be dangerous. Overcoming these barriers will require integrating insights from basic science, high-altitude physiology, clinical medicine, and sports technology. Here, we explore the foundations of this nascent field and outline a path to determine how chronic continuous hypoxia can be safely, effectively, and practically delivered to patients.

Ri-Li Ge. Medical problems of chronic hypoxia in highlanders living on the tibetan plateau. High Alt Med Biol. 00:00-00, 2024.-Health issues at high altitudes arise due to the lower atmospheric pressure and subsequent reduction in the partial pressure of oxygen in ambient air. While much research has been published on health problems of lowlanders who move to high altitudes, less is known about the medical challenges faced by long-term and permanent high-altitude residents, especially in the Qinghai-Tibetan plateau. In this review, we briefly summarized the chronic hypoxia-related health issues in highlanders, focusing on the specific population of the Qinghai-Tibetan plateau. It deals with important health problems for highlanders, including the main disease categories, from chronic mountain sicknesses and pulmonary hypertension (PH) to kidney, neurocognitive impairments, perinatal problems, and congenital heart defect. However, the most hallmark of disorders is excessive erythrocytosis associated with specific symptoms and signs, and high-altitude heart disease is characterized by excessive PH, right ventricular hypertrophy, and right heart failure. We also provide information on potential treatment strategies, including some traditional Tibetan medical practices and also a combination of Western medicine and traditional Chinese medicine to prevent and treat these conditions effectively. This mini-review is heavily based on a couple of decades of research carried out by Chinese high-altitude medical research groups at the Qinghai-Tibetan Plateau. We believe that this review will provide valuable perspective to researchers whose study interest and base lie in high altitude.

Evidence has shown that the incidence of bacillary dysentery (BD) is associated with climatic factors. However, the lagged effects of climatic factors on BD are still unclear, especially lacking research evidence from arid and semi-arid regions. Therefore, this study aims to add new insights into this research field.

Spatial autocorrelation, time series analysis and spatiotemporal scans were used to perform descriptive analyses of BD cases from 2009 to 2019. On the basis of monthly data from 2015 to 2019, multivariable distributed lag non-linear models were used to investigate the lagged effects of climatic factors on BD.

The hot spots for BD incidence are gradually decreasing and becoming increasingly concentrated in the southern part of Gansu Province. The maximum cumulative relative risks for monthly average temperature, sunshine duration, average relative humidity and precipitation were 3.21, 1.64, 1.55 and 1.41, respectively. The lagged effects peaked either in the current month or with a 1-month lag, and the shape of the exposure-response curve changed with the increase in maximum lag time. After stratification by per capita gross domestic product, there were differences in the effects.

Climatic factors can influence the incidence of BD, with effects varying across different lag times. It is imperative to vigilantly track the disparities in the incidence of BD attributable to economic factors.

Many studies on the adaptability of Tibetan sheep to hypoxia have been reported, but little attention has been paid to the reproduction of Tibetan sheep living at an altitude of more than 4000 m. In this study, the ovaries of Alpine Merino sheep (AM) living in middle-high altitude areas (2500 m) and the ovaries of Gangba Tibetan sheep (GB) and Huoba Tibetan sheep (HB) living in ultra-high altitude areas (4400 m or more) were collected. Through morphological, transcriptomics and metabolomics, the effects of ultra-high altitude areas on Tibetan sheep ovarian development and the molecular mechanism of sheep's adaptability to ultra-high altitude environment were explored. The results showed that the number of granulosa cells in AM was significantly higher than that in GB and HB. The transcriptome revealed several genes related to follicular development, such as DAPL1, IGFBP1, C5, GPR12, STRA6, BMPER, etc., which were mainly enriched in related pathways such as cell growth and development. Through metabolomics analysis, it was found that the differential metabolites between the three groups of sheep were mainly lipids and lipid-like small molecules, such as Glycerol 3-Phosphate, PC (16: 0 / 18: 3 (9Z, 12Z, 15Z)), mainly enriched in lipid metabolism and other related pathways. The results of combined analysis showed that Tryptophan metabolism and Steroid hormone biosynthesis may have a significant effect on Tibetan sheep follicular development. Some genes (including HSD17B7, CYP11A1, CYP19, HSD3B1, CYP17, etc.) and some metabolites (including Cortisone, 2-Methoxyestrone, etc.) are enriched in these pathways, regulating ovarian and follicular development by affecting estrogen, progesterone, etc.. The results further revealed the molecular mechanism of Tibetan sheep to adapt to the ultra-high altitude environment and maintain normal ovarian and follicular development through the regulation of genes and metabolites.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Currently, ALS is conceived as the result of the interaction between genetics, environmental factors, and aging. This study analyzed the spatial and temporal patterns of ALS in Spain, delving into the potential relationships between altitude, land cover, and this disease.

ALS death data were collected over a 19-year period, including information on sex, age and municipality of residence. The standardized mortality rate was calculated for each municipality of residencia, and Anselin's local Moran's I statistic was used to identify clusters of high and low incidence. Altitude data were sourced from the Copernicus Land Monitoring Services, while land cover data came from CORINE satellite images and national agricultural statistics.

The average annual incidence of ALS deaths among adults was 2.5 per 100,000 people. Higher mortality rates were noted in males (2.8) than in females (2.3), with both sexes exhibiting a rising mortality trend in a temporal analysis. Cluster analysis revealed that high mortality areas were mostly located in the North and Northeast of the country. Municipalities in these clusters had significantly lower median altitudes and larger areas of Permanently Irrigated Arable Land and Broad-Leaved Forest.

This study provides new evidence about the increase in ALS cases in European countries during the last decades, reporting for the first time altitude and certain agricultural land uses as potential geographic determinants of the disease.

The study reports on a high-altitude EEG dataset comprising 64-channel EEG signals from 23 subjects, aiming at achieving a finer-grained assessment of hypoxia levels. Four hypoxia levels were induced by creating a gradient of oxygen partial pressure through changes in altitude and external hypoxia stimulation. The dataset was collected in a hypoxic chamber that simulates altitude changes, allowing for a refined classification of different hypoxia levels based on ranges of oxygen saturation. The total recorded EEG data amounts to approximately 10.25 hours. Validation results indicate that the four hypoxia levels can be effectively recognized using EEG signals. Compared to binary classification, our fine-grained dataset allows for more precise detection of hypoxia levels. This dataset is anticipated to have significant research and practical value in developing accurate methods for identifying hypoxia levels. As a valuable and standardized resource, it will enable extensive analysis and comparison for researchers in the field of high-altitude hypoxia.

Un-acclimatized individuals may experience acute altitude illness. Thus, the current study investigated the impact of short-term intermittent normobaric hypoxia (NH) combined with light exercise on the acclimatization of cardiorespiratory function to altitude in inactive adults.

This quasi-experimental study recruited 10 inactive university students (age: 26.3 ± 2.53 years). All participants were instructed to perform light exercise while exposed to intermittent NH (15%) (2 h/d) for 2 weeks continuously. The heart rate (HR), relative oxygen consumption (VO2 mL/kg/min), minute ventilation (VE), VO2/HR, and respiratory frequency (RF) were measured.

Results illustrated a significant improvement in participants' cardiorespiratory functions by 10 days after exposure to NH, as compared to day 1 of exposure, based on their HR, RF, and VE responses at rest and HR, RF, VE, VO2, VO2/kg, and VO2/HR during light exercise. Resting-state values had returned to the pre-NH exposure levels after 10 days of intermittent NH exposure. Furthermore, values measured during light exercise were significantly decreased on days 10 and 14 as compared to day 1 of NH exposure.

This study concluded that as few as 10 days of exposure to intermittent NH (pO2 = 15%) combined with light exercise may improve the acclimation to NH of 15% pO2 in inactive adults.

Berkemeier, Quint N., Michael R. Deyhle, James J. McCormick, Kurt A. Escobar, and Christine M. Mermier. The potential interplay between HIF-1α, angiogenic, and autophagic signaling during intermittent hypoxic exposure and exercise High Alt Med Biol. 25:326-336, 2024.-Environmental hypoxia as a result of decreased barometric pressure upon ascent to high altitudes (>2,500 m) presents increased physiological demands compared with low altitudes, or normoxic environments. Competitive athletes, mountaineers, wildland firefighters, military personnel, miners, and outdoor enthusiasts commonly participate in, or are exposed to, forms of exercise or physical labor at moderate to high altitudes. However, the majority of research on intermittent hypoxic exposure is centered around hematological markers, and the skeletal muscle cellular responses to exercise in hypoxic environments remain largely unknown. Two processes that may be integral for the maintenance of cellular health in skeletal muscle include angiogenesis, or the formation of new blood vessels from preexisting vasculature and autophagy, a process that removes and recycles damaged and dysfunctional cellular material in the lysosome. The purpose of this review is to is to examine the current body of literature and highlight the potential interplay between low-oxygen-sensing pathways, angiogenesis, and autophagy during acute and prolonged intermittent hypoxic exposure in conjunction with exercise. The views expressed in this paper are those of the authors and do not reflect the official policy of the Department of Army, DOD, DOE, ORAU/ORISE or U.S. Government.

Individuals residing in plateau regions are susceptible to pulmonary hypertension (PH) and there is an urgent need for a prediction nomogram to assess the risk of PH in this population. A total of 6603 subjects were randomly divided into a derivation set and a validation set at a ratio of 7:3. Optimal predictive features were identified through the least absolute shrinkage and selection operator regression technique, and nomograms were constructed using multivariate logistic regression. The performance of these nomograms was evaluated and validated using the area under the curve (AUC), calibration curves, the Hosmer-Lemeshow test, and decision curve analysis. Comparisons between nomograms were conducted using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices. NomogramI was established based on independent risk factors, including gender, Tibetan ethnicity, age, incomplete right bundle branch block (IRBBB), atrial fibrillation (AF), sinus tachycardia (ST), and T wave changes (TC). The AUCs for NomogramI were 0.716 in the derivation set and 0.718 in the validation set. NomogramII was established based on independent risk factors, including Tibetan ethnicity, age, right axis deviation, high voltage in the right ventricle, IRBBB, AF, pulmonary P waves, ST, and TC. The AUCs for NomogramII were 0.844 in the derivation set and 0.801 in the validation set. Both nomograms demonstrated satisfactory clinical consistency. The IDI and NRI indices confirmed that NomogramII outperformed NomogramI. Therefore, the online dynamic NomogramII was established to predict the risks of PH in the plateau population.

To investigate the characteristics of balance and gait functions in Generalized Joint Hypermobility (GJH) subjects residing in high-altitude areas.

This study included 61 university students (28 with GJH and 33 healthy controls) all from the high-altitude region of Linzhi, Tibet Autonomous Region. The Riablo™ wearable intelligent rehabilitation assessment and training system was used to assess static balance (with eyes open and closed) and gait function (during flat walking) in both groups.

Compared to healthy subjects, GJH subjects exhibited significantly impaired balance, indicated by an increased distance of the center of pressure position from the ideal center of gravity(EO: P = 0.007, EC: P = 0.031) and greater amplitude of center of pressure displacements (EO: P = 0.043, EC: P = 0.032). Gait velocity(P = 0.007), stride length(P = 0.012), and swing stance phase of the gait cycle(P = 0.046) were significantly reduced in GJH subjects compared to healthy subjects. A significant increase in the flat-foot phase of the gait cycle(P = 0.022) was observed in GJH subjects compared to healthy subjects.

The current study demonstrated that GJH subjects residing in high-altitude areas exhibit impairments in balance and gait, providing a basis for training and prevention strategies tailored for this population. And this study used the wearable intelligent rehabilitation evaluation and training system in high-altitude areas, providing methodological references for scientific research on balance and gait function under non laboratory conditions.

Controlled Trials No.102772023RT133, Registered 13 October 2023.

The pathophysiology of pulmonary hypertension is complex and multifactorial. It is a disease characterized by increased pulmonary vascular resistance at the level due to sustained vasoconstriction and remodeling of the pulmonary arteries, which triggers an increase in the mean pulmonary artery pressure and subsequent right ventricular hypertrophy, which in some cases can cause right heart failure. Hypoxic pulmonary hypertension (HPH) is currently classified into Group 3 of the five different groups of pulmonary hypertensions, which are determined according to the cause of the disease. HPH mainly develops as a product of lung diseases, among the most prevalent causes of obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), or hypobaric hypoxia due to exposure to high altitudes. Additionally, cardiometabolic risk factors converge on molecular mechanisms involving overactivation of the mammalian target of rapamycin (mTOR), which correspond to a central axis in the development of HPH. The aim of this review is to summarize the role of mTOR in the development of HPH associated with metabolic risk factors and its therapeutic alternatives, which will be discussed in this review.

High-altitude pulmonary edema (HAPE) is a fatal threat for sojourners who ascend rapidly without sufficient acclimatization. Acclimatized sojourners and adapted natives are both insensitive to HAPE but have different physiological traits and molecular bases. In this study, based on GSE52209, the gene expression profiles of HAPE patients were compared with those of acclimatized sojourners and adapted natives, with the common and divergent differentially expressed genes (DEGs) and their hub genes identified, respectively. Bioinformatic methodologies for functional enrichment analysis, immune infiltration, diagnostic model construction, competing endogenous RNA (ceRNA) analysis and drug prediction were performed to detect potential biological functions and molecular mechanisms. Next, an array of in vivo experiments in a HAPE rat model and in vitro experiments in HUVECs were conducted to verify the results of the bioinformatic analysis. The enriched pathways of DEGs and immune landscapes for HAPE were significantly different between sojourners and natives, and the common DEGs were enriched mainly in the pathways of development and immunity. Nomograms revealed that the upregulation of TNF-α and downregulation of RPLP0 exhibited high diagnostic efficiency for HAPE in both sojourners and natives, which was further validated in the HAPE rat model. The addition of TNF-α and RPLP0 knockdown activated apoptosis signaling in endothelial cells (ECs) and enhanced endothelial permeability. In conclusion, TNF-α and RPLP0 are shared biomarkers and molecular bases for HAPE susceptibility during the acclimatization/adaptation/maladaptation processes in sojourners and natives, inspiring new ideas for predicting and treating HAPE.

Patients living in high altitudes are often deprived of total knee arthroplasty (TKA) due to logistic reasons, economic, and social challenges in performing surgical procedures for management of knee pain. Surgical procedures in high-altitude dwellers have associated risk of deep venous thrombosis/pulmonary embolism (DVT/PE). In patients undergoing these procedures at lower altitudes, return to high altitudes can cause high-altitude pulmonary edema (HAPE). We share our experience of performing TKA in high-altitude dwellers by setting up a surgical camp at 11,000 feet.

A retrospective assessment of patients undergoing total knee arthroplasty at a camp set up at 11,000 feet between 2014 and 2020 was undertaken. Follow-up data of patients which included clinical assessment by the Knee Society Score (KSS) and complications like DVT, infection, residual deformity, etc. were included in the study. Radiographic evaluation to look for evidence of implant loosening was also inculcated.

132 patients (202 knee joints in 50 male and 82 female patients) underwent TKA during annual camps. The average follow-up of patients was 60 months. Mean pre-operative KSS was 38, which was increased to 83 at 1-year follow-up post-surgery. There was no evidence of DVT or superficial or deep infection in any patient in the post-operative period.

With this study, we want to highlight that total knee arthroplasty can be safely performed at high altitudes and remote areas with limited health facilities. We believe it is a safer and more convenient prospect for the residents of high-altitude regions.

III.

After a 920-day hiatus, COVID-19 resurged in the Tibet Autonomous Region of China in August 2022. This study compares the characteristics of COVID-19 between high-altitude residents and newcomers, as well as between newcomers and lowlanders.

This multi-center cohort study conducted at the Third People's Hospital of Tibet Autonomous Region and Beijing University Shenzhen Hospital, included 520 high-altitude resident patients, 53 high-altitude newcomer patients, and 265 lowlander patients infected with the Omicron variant. Initially, we documented epidemiological, clinical, and treatment data across varying residency at admission. We compared the severity of COVID-19 and various laboratory indicators, including hemoglobin concentration and SpO2%, over a 14-day period from the date of the first positive nucleic acid test, as well as the differences in treatment methods and disease outcomes between highlanders and high-altitude newcomers. We also compared several characteristics of COVID-19 between high-altitude newcomers and lowlanders. Univariate analysis, multivariable logistic regression, and the generalized linear mixed model were utilized for the analysis.

No fatalities were observed. The study found no significant differences in COVID-19 severity or in the physiological measures of hemoglobin concentration and SpO2% between high-altitude and lowland residents. Similarly, there were no statistically significant differences in the values or trends of hemoglobin and SpO2% between high-altitude residents and newcomers throughout the 14-day observation period. However, compared to age- and sex-matched lowlander patients (1:5 ratio), high-altitude newcomers exhibited higher heart rates, respiratory rates, and average hemoglobin concentrations, along with lower platelet counts. There were no significant differences in hospital stays between the two groups.

High-altitude residents and newcomer patients exhibit clinical similarities. However, the clinical characteristics of high-altitude newcomers and lowlander patients differ due to the impact of the high-altitude environment. These results highlight potential considerations for public health strategies in high-altitude regions such as Tibet.

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.

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.

High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory-based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end-tidal carbon dioxide (P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) against peripheral oxygen saturation (S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self-administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morningP ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ andS p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ measurements were collected on 46 acetazolamide-free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. HIGHLIGHTS: What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide-free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

To investigate the short-term changes in chest CT images of low-altitude populations after entering a high-altitude environment.

Chest CT images of 3,587 people from low-altitude areas were obtained within one month of entering a high-altitude environment. Abnormal CT features and clinical symptoms were analyzed.

Besides acute high-altitude pulmonary edema, the incidence of soft tissue space pneumatosis was significantly higher than that in low-altitude areas. Pneumatosis was observed in the mediastinum, cervical muscle space, abdominal cavity, and spinal cord epidural space, especially the mediastinum.

In addition to acute high-altitude pulmonary edema, spontaneous mediastinal emphysema often occurs when individuals in low-altitude areas adapt to the high-altitude environment of cold, low-pressure, and hypoxia. When the gas escapes to the abdominal cavity, it is easy to be misdiagnosed as gastrointestinal perforation. It is also not uncommon for gas accumulation to escape into the epidural space of the spinal cord. The phenomenon of gas diffusion into distant tissue space and the mechanism of gas escape needs to be further studied.

Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS.

Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed.

We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism.

The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.

Background: During the COVID-19 pandemic, emergency departments were overcrowded with critically ill patients, and many providers were confronted with ethical dilemmas in assigning respiratory support to them due to scarce resources. Quick tools for evaluating patients upon admission were necessary, as many existing scores proved inaccurate in predicting outcomes. The ROX Index (RI), a rapid and straightforward scoring system reflecting respiratory status in acute respiratory failure patients, has shown promise in predicting outcomes for COVID-19 patients. The 24 h difference in the RI accurately gauges mortality and the need for invasive mechanical ventilation (IMV) among patients with COVID-19. Methods: Study design: Prospective cohort study. A total of 204 patients were admitted to the emergency department from May to August 2020. Data were collected from the clinical records. The RI was calculated at admission and 24 h later, and the difference was used to predict the association with mortality and the need for IMV, a logistic regression model was used to adjust for age, sex, presence of comorbidities, and disease severity. Finally, the data were analyzed using ROC. Results: The difference in respiratory RI between admission and 24 h is a good predictor for death (AUC 0.92) and for mechanic ventilation (AUC: 0.75). Each one-unit decrease in the RI difference at 24 h was associated with an odds ratio of 1.48 for the risk of death (95%CI: 1.31-1.67) and an odds ratio of 1.16 for IMV (95% IC: 1.1-1.23). Conclusions: The 24 h variation of RI is a good prediction tool to allow healthcare professionals to identify the patients who will benefit from invasive treatment, especially in low-resource settings.

High-altitude populations exhibit distinct cellular, respiratory, and cardiovascular phenotypes, some of which provide adaptive advantages to hypoxic conditions compared to populations with sea-level ancestry. Studies performed in populations with a history of high-altitude residence, such as Tibetans, support the idea that many of these phenotypes may be shaped by genomic features that have been positively selected for throughout generations. We hypothesize that such traits observed in Tibetans at high altitude also occur in Tibetans living at intermediate altitude, even in the absence of severe sustained hypoxia.

We studied individuals of high-altitude ancestry (Tibetans, n = 17 females; n = 12 males) and sea-level ancestry (Han Chinese, n = 6 females; n = 10 males), both who had been living at ∼1300 m (∼4327 ft) for at least 18 months. We measured hemoglobin concentration ([Hb]), hypoxic ventilatory response (HVR), and hypoxic heart rate response (HHRR) with end-tidal CO2 (PetCO2) held constant (isocapnia) or allowed to decrease with hypoxic hyperventilation (poikilocapnia). We also quantified the contribution of CO2 on ventilation and heart rate by calculating the differences of isocapnic versus poikilocapnic hypoxic conditions (Δ V ˙ I /ΔPetCO2 and ΔHR/ΔPetCO2, respectively).

Male Tibetans had lower [Hb] compared to Han Chinese males (p < 0.05), consistent with reports for individuals from these populations living at high altitude and sea level. Measurements of ventilation (resting ventilation, HVR, and PetCO2) were similar for both groups. Heart rate responses to hypoxia were similar in both groups during isocapnia; however, HHRR in poikilocapnia was reduced in the Tibetan group (p < 0.03), and the heart rate response to CO2 in hypoxia was lower in Tibetans relative to Han Chinese (p < 0.01).

These results suggest that Tibetans living at intermediate altitude have blunted cardiac responses in the context of hypoxia. Hence, only some of the phenotypes observed in Tibetans living at high altitude are observed in Tibetans living at intermediate altitude. Whereas blunted cardiac responses to hypoxia is revealed at intermediate altitudes, manifestation of other physiological adaptations to high altitude may require exposure to more severe levels of hypoxia.

HIF-1α, a key player in medical science, holds immense significance in therapeutic approaches. This review delves into its complex dynamics, emphasizing the delicate balance required for its modulation. HIF-1α stands as a cornerstone in medical research, its role extending to therapeutic strategies. This review explores the intricate interplay surrounding HIF-1α, highlighting its critical involvement and the necessity for cautious modulation.

In sickle cell disease (SCD), HIF-1α's potential to augment fetal hemoglobin (HbF) production and mitigate symptoms is underscored. Furthermore, its role in cancer is examined, particularly its influence on survival in hypoxic tumor microenvironments, angiogenesis, and metastasis. The discussion extends to the intricate relationship between HIF-1α modulation and cancer risks in SCD patients, emphasizing the importance of balancing therapeutic benefits and potential hazards.

Managing HIF-1α modulation in SCD patients requires a nuanced approach, considering therapeutic potential alongside associated risks, especially in exacerbating cancer risks. An evolutionary perspective adds depth, highlighting adaptations in populations adapted to low-oxygen environments and aligning cancer cell metabolism with primitive cells. The role of HIF-1α as a therapeutic target is discussed within the context of complex cancer biology and metabolism, acknowledging varied responses across diverse cancers influenced by intricate evolutionary adaptations.

When exposed to high-altitude environments, the cardiovascular system undergoes various changes, the performance and mechanisms of which remain controversial.

To summarize the latest research advancements and hot research points in the cardiovascular system at high altitude by conducting a bibliometric and visualization analysis.

The literature was systematically retrieved and filtered using the Web of Science Core Collection of Science Citation Index Expanded. A visualization analysis of the identified publications was conducted employing CiteSpace and VOSviewer.

A total of 1674 publications were included in the study, with an observed annual increase in the number of publications spanning from 1990 to 2022. The United States of America emerged as the predominant contributor, while Universidad Peruana Cayetano Heredia stood out as the institution with the highest publication output. Notably, Jean-Paul Richalet demonstrated the highest productivity among researchers focusing on the cardiovascular system at high altitude. Furthermore, Peter Bärtsch emerged as the author with the highest number of cited articles. Keyword analysis identified hypoxia, exercise, acclimatization, acute and chronic mountain sickness, pulmonary hypertension, metabolism, and echocardiography as the primary research hot research points and emerging directions in the study of the cardiovascular system at high altitude.

Over the past 32 years, research on the cardiovascular system in high-altitude regions has been steadily increasing. Future research in this field may focus on areas such as hypoxia adaptation, metabolism, and cardiopulmonary exercise. Strengthening interdisciplinary and multi-team collaborations will facilitate further exploration of the pathophysiological mechanisms underlying cardiovascular changes in high-altitude environments and provide a theoretical basis for standardized disease diagnosis and treatment.

The purpose of this study is to investigate the serum inflammatory factors in patients with high-altitude polycythemia (HAPC) and their correlation with cognitive function. The subjects were recruited and placed into a HAPC group and control group. Serum samples were collected, and inflammatory factors (interleukin-1beta [IL-1β], monocyte chemoattractant protein-1 [MCP-1], and tumor necrosis factor-alpha [TNF-α]) were measured using ELISA kits. The mini-mental State Examination (MMSE) was used to assess cognitive function. According to the MMSE scores, HAPC group was further divided into normal cognitive function group (HNCF) and cognitive dysfunction group (HCDF). In comparison with the control group, the MMSE scores in the HAPC group were significantly low (P < .05), whereas the serum levels of IL-1β, MCP-1, and TNF-α were significantly high (P < .01). Among the HAPC group (n = 60), 21 belonged to the HCDF and 39 belonged to the HNCF. Compared with the HNCF, the IL-1β, MCP-1, and TNF-α in the HCDF were significantly increased (P < .01). The Pearson correlation analysis showed that inflammatory factors were positively correlated with hemoglobin, and negatively correlated with MMSE. Serum inflammatory cytokines IL-1, MCP-1, and TNF-α were increased in HAPC, and HAPC exhibited cognitive dysfunction. Considering chronic hypoxia environment influences the change of the red blood cell metabolic and inflammatory factor, red blood cells and inflammatory factor in plateau is likely to be affected by patients with vascular lesions, increase cognitive impairment.

The complexity of indoor particulate exposure intensifies at higher altitudes owing to the increased lung capacity that residents develop to meet the higher oxygen demands. Altitude variations impact atmospheric pressure and alter particulate dynamics in ambient air and the human respiratory tract, complicating particulate inhalation. This study assessed the fraction of PM2.5 and PM10 entering small airways. This assessment covered an altitude range from 400 m above sea level to 3650 m, and an in vitro respiratory tract model was used. The experimental results confirmed that with increasing altitude, the penetration fractions of PM2.5 and PM10 significantly increased from 0.133 ± 0.031 and 0.141 ± 0.045 to 0.404 ± 0.159 and 0.353 ± 0.132, respectively. Additionally, the computational fluid dynamics simulation results revealed that among particles with sizes of 0.1 to 10 µm, the 7.5-μm particles exhibited the most substantial reduction in deposition in the upper airway, displaying a decrease of 6.27%. Our findings underscore the health risks faced by low-altitude residents during acclimatization to higher altitudes, as they experience heightened exposure to particulate matter sources.

In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048 m altitude, and has made it mandatory for conditions equivalent to more than 3657 m altitude.

We hypothesized that hypobaric-hyperoxic civilian commercial and private flight conditions with supplemental oxygen in a flight simulation in a hypobaric chamber at 2500 m and 4500 m equivalent altitude would cause significant oxidative stress in healthy individuals.

Twelve healthy, COVID-19-vaccinated (third portion of vaccination 15 months before study onset) subjects (six male, six female, mean age 35.7 years) from a larger cohort were selected to perform a 3 h flight simulation in a hypobaric chamber with increasing supplemental oxygen levels (35%, 50%, 60%, and 100% fraction of inspired oxygen, FiO2, via venturi valve-equipped face mask), switching back and forth between simulated altitudes of 2500 m and 4500 m. Arterial blood pressure and oxygen saturation were constantly measured via radial catheter and blood samples for blood gases taken from the catheter at each altitude and oxygen level. Additional blood samples from the arterial catheter at baseline and 60% oxygen at both altitudes were centrifuged inside the chamber and the serum was frozen instantly at -21 °C for later analysis of the oxidative stress markers malondialdehyde low-density lipoprotein (M-LDL) and glutathione-peroxidase 1 (GPX1) via the ELISA test.

Eleven subjects finished the study without adverse events. Whereas the partial pressure of oxygen (PO2) levels increased in the mean with increasing oxygen levels from baseline 96.2 mm mercury (mmHg) to 160.9 mmHg at 2500 m altitude and 60% FiO2 and 113.2 mmHg at 4500 m altitude and 60% FiO2, there was no significant increase in both oxidative markers from baseline to 60% FiO2 at these simulated altitudes. Some individuals had a slight increase, whereas some showed no increase at all or even a slight decrease. A moderate correlation (Pearson correlation coefficient 0.55) existed between subject age and glutathione peroxidase levels at 60% FiO2 at 4500 m altitude.

Supplemental oxygen of 60% FiO2 in a flight simulation, compared to flying in cabin pressure levels equivalent to 2500 m-4500 m altitude, does not lead to a significant increase or decrease in the oxidative stress markers M-LDL and GPX1 in the serum of arterial blood.

The illnesses associated with changes in barometric pressure can be classified into three types: acute mountain sickness, high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema. HAPE is a rare form of pulmonary edema that occurs in susceptible individuals after arriving at altitudes over 2500 m above sea level (m). Only a few studies have reported classical HAPE among children with underlying cardiopulmonary comorbidities. In this study, we report two pediatric cases of classical HAPE that occurred immediately upon arriving at Abha city (with an average elevation of 2270 m above sea level). Notably, both patients possessed underlying chronic lung diseases, raising crucial questions about susceptibility factors and the early onset manifestations of HAPE.

Two pediatric cases of HAPE are presented. The first patient, with a medical history of repaired right congenital diaphragmatic hernia and subsequent right lung hypoplasia, developed HAPE following their ascent to a high altitude. The second patient, diagnosed with diffuse lung disease of unknown etiology, experienced HAPE after a rapid high-altitude ascent. Both patients resided in low-altitude areas prior to ascent. The initial emergency room assessment revealed that both patients had severe hypoxia with respiratory distress that mandated the initiation of respiratory support and 100% oxygen therapy. They required intensive care unit admission, improved after 5 days of hospitalization, and were sent home in good condition.

HAPE is a complex, potentially life-threatening high-altitude illness with diverse clinical presentations and variable risk factors. This case report sheds light on a potential predisposition factor-pre-existing lung disease-in children experiencing severe HAPE. While further validation is crucial, this valuable insight opens doors for improved preventative strategies and informed medical decisions for children with pre-existing lung conditions traveling to high altitudes.

Ambient air pollution could increase the risk of hypertension; however, evidence regarding the relationship between long-term exposure to particulate matter and elevated blood pressure in plateau areas with lower pollution levels is limited.

We assessed the associations of long-term exposure to particulate matter (PM, PM1, PM2.5, and PM10) with hypertension, diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse pressure (PP) in 4.235 Tibet adults, based on the baseline of the China multi-ethnic cohort study (CMEC) in Lhasa city, Tibet from 2018-19. We used logistic regression and linear regression models to evaluate the associations of ambient PM with hypertension and blood pressure, respectively.

Long-term exposure to PM1, PM2.5, and PM10 is positively associated with hypertension, DBP, and SBP, while negatively associated with PP. Among these air pollutants, PM10 had the strongest effect on hypertension, DBP, and SBP, while PM2.5 had the strongest effect on PP. The results showed for hypertension odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.58, 2.51 per interquartile range (IQR) μg/m3 increase in PM1, OR = 1.93; 95% CI = 1.55, 2.40 per IQR μg/m3 increase in PM2.5, and OR = 2.12; 95% CI = 1.67, 2.68 per IQR μg/m3 increase in PM10.

Long-term exposure to ambient air pollution was associated with an increased risk of hypertension, elevated SBP and DBP levels, and decreased PP levels. To reduce the risk of hypertension and PP reduction, attention should be paid to air quality interventions in plateau areas with low pollution levels.

Background: Optic nerve sheath diameter (ONSD) increases significantly at high altitudes, and is associated with the presence and severity of acute mountain sickness (AMS). Exposure to hypobaria, hypoxia, and coldness when hiking also impacts intraocular pressure (IOP). To date, little is known about ocular physiological responses in trekkers with myopia at high altitudes. This study aimed to determine changes in the ONSD and IOP between participants with and without high myopia (HM) during hiking and to test whether these changes could predict symptoms of AMS. Methods: Nine participants with HM and 18 without HM participated in a 3-day trek of Xue Mountain. The ONSD, IOP, and questionnaires were examined before and during the trek of Xue Mountain. Results: The ONSD values increased significantly in both HM (p = 0.005) and non-HM trekkers (p = 0.018) at an altitude of 1,700 m. In the HM group, IOP levels were greater than those in the non-HM group (p = 0.034) on the first day of trekking (altitude: 3,150 m). No statistically significant difference was observed between the two groups for the values of ONSD. Fractional changes in ONSD at an altitude of 1,700 m were related to the development of AMS (r pb = 0.448, p = 0.019) and the presence of headache symptoms (r pb = 0.542, p = 0.004). The area under the ROC curve for the diagnostic performance of ONSD fractional changes at an altitude of 1,700 m was 0.859 for predicting the development of AMS and 0.803 for predicting the presence of headache symptoms. Conclusion: Analysis of changes in ONSD at moderate altitude could predict AMS symptoms before an ascent to high altitude. Myopia may impact physiological accommodation at high altitudes, and HM trekkers potentially demonstrate suboptimal regulation of aqueous humor in such environments.

Tsantan Sumtang (TS), originated from the Four Tantras, is an empirical Tibetan medicine prescription, which has been widely used for treating cardiovascular diseases in the clinic in Qinghai Province of China. Our previous studies found that TS alleviated hypoxia-induced pulmonary hypertension (HPH) in rats. However, the effect and bioactive fractions of TS on hypoxia-injured pulmonary vascular endothelium are unknown.

To investigate the effect, bioactive fractions and pharmacological mechanism of TS on hypoxia-injured pulmonary vascular endothelium in vivo and in vitro.

In vivo studies, HPH animal model was established, and TS was administrated for four weeks. Then, hemodynamic indexes, ex vivo pulmonary artery perfusion experiment, morphological characteristics, nitric oxide (NO) production, and the protein expression of protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) and AMP-activated protein kinase (AMPK)/eNOS signaling were determined. In vitro studies, 1% O2-induced pulmonary artery endothelial cells (PAECs) injury model was applied for screening bioactive fractions of TS by cell proliferation assay and NO production measurement. The associated proteins of AKT/eNOS signaling were further measured to elucidate underlying mechanism of bioactive fraction of TS via using phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002. Ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS) was used to reveal the chemical profile of bioactive fraction of TS.

TS showed protective effect on the integrity of distal pulmonary arterial endothelium in HPH rats. Tsantan Sumtang dilated pulmonary arterial rings in HPH rats. TS enhanced NO bioavailability in lung tissue via regulating AKT/eNOS signaling. Furthermore, in the cellular level, cell viability as well as NO content of hypoxia-injured PAECs were elevated by fraction 17 of water extract of TS (WTS), through activating the AKT/eNOS signaling. Ellagic acid could be one of compositions in fraction 17 of WTS to produce NO in hypoxia-injured PAECs.

TS restored pulmonary arterial endothelial function in HPH rats. The bioactive fraction 17 was screened, which protected hypoxia-injured PAECs via upregulating AKT/eNOS signaling.