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An improved formula for standard hypoxia tolerance time to evaluate hypoxic tolerance in mice

Military Medical Research 2019年第2期6卷 111-116页

作者： Gang Xu Yu-Qi Gao Yi-Xing Gao Gang Wu Jian-Yang Zhang Wen-Xiang Gao institute of medicine and Hygienic equipment for high altitude region College of High Altitude Military MedicineArmy Medical University(Third Military Medical University)Chongqing400038China Key Laboratory of high altitude medicine People’s Liberation ArmyChongqing400038China

Background: Hypoxia is a primary cause of mountain sickness and a common pathological condition in patients with heart failure, shock, stroke, and chronic obstructive pulmonary disease(COPD). Thus far, little advancement in countering hypoxic damage has been achieved, and one of the main reasons is the absence of an ideal algorithm or calculation method to normalize hypoxia tolerance scores when evaluating an animal model. In this study, we improved a traditional calculation formula for assessment of hypoxia ***: We used a sealed bottle model in which the oxygen is gradually consumed by a mouse inside. To evaluate the hypoxia tolerance of mice, the survival time(ST) of the mouse is recorded and was used to calculate standard hypoxia tolerance time(STT) and adjusted standard hypoxia tolerance time(ASTT). Mice administered with methazolamide and saline were used as positive and negative controls, ***: Since mice were grouped according to either body weight(BW) or bottle volume, we found a strongly negative correlation between STT and BW instead of between STT and bottle volume, suggesting that different BWs could cause false positive or negative errors in the STT results. Furthermore, both false positive and negative errors could be rectified when ASTT was used as the evaluation index. Screening for anti-hypoxic medicines by using mice as the experimental subjects would provide more credible results with the improved ASTT method than with the STT ***: ASTT could be a better index than STT for the evaluation of hypoxia tolerance abilities as it could eliminate the impact of animal BW.

关键词： Hypoxia Standard hypoxic tolerance time Mice model Body weight

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DL-3-n-butylphthalide improved physical and learning and memory performance of rodents exposed to acute and chronic hypobaric hypoxia

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Military Medical Research 2022年第1期9卷 1-11页

作者： Gang Xu Yi-Kun Shi Bin-Da Sun Lu Liu Guo-Ji E Shu He Jian-Yang Zhang Bao Liu Qiu Hu Jian Chen Yu-Qi Gao Er-Long Zhang institute of medicine and equipment for high altitude region College of High Altitude Military MedicineArmy Medical UniversityChongqing 400038China Key Laboratory of Extreme Environmental medicine Ministry of Education of ChinaChongqing 400038China Key Laboratory of high altitude medicine People's Liberation ArmyChongqing 400038China

Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic ***,the role of NBP in animals with hypobaric hypoxia has not been *** study investigated the effects of NBP on rodents with acute and chronic hypobaric ***:Sprague-Dwaley rats and Kunming mice administered with NBP(0,60,120,and 240 mg/kg for rats and 0,90,180,and 360 mg/kg for mice)were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were ***,the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments,conducted at 5800 m for 3 days or 20 days,to evaluate changes in physical *** frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment,conducted at 5800 m for 6 days or 27 days,to evaluate changes in learning and memory *** levels were measured in the gastrocnemius muscle and malonaldehyde(MDA),superoxide dismutase(SOD),hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),and lactate were detected in sera of rats,and routine blood tests were also ***:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance *** time and distance to exhaustion for mice(NBP,90 mg/kg)and time to exhaustion for rats(NBP,120 and 240 mg/kg)significantly increased under conditions of acute hypoxia compared with control *** treatment also significantly increased the time to exhaustion for rats when exposed to chronic ***,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute ***,the levels of MDA and H_(2)O_(2) decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic ***,ATP levels in the gastrocnemius muscle significantly incre

关键词： DL-3-n-butylphthalide Hypobaric hypoxia Physical function Learning and memory function Oxidative stress Energy metabolism

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Therapeutic intervention against deacclimatization to high altitude

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中国应用生理学杂志 2013年第6期29卷 512-517页

作者： Yin-hu WANG Qi-quan ZHOU Sheng-hong YANG Yan WANG Bin LI Chao-liang LONG Hai WANG institute of high altitude Diseases 18th Hospital of PLA Department of high altitude Disease College of High Altitude Military Medicine the Third Military Medical University Key Laboratory of Military Environmental medicine Institute of Health and Environmental MedicineAcademy of Military Medical Sciences

The incidence of deacclimatization to high altitude syndrome(DAHAS) prevailed up to 80% in highland troops, and 100% in manual workers, and severe DAHAS could significantly affects patients' health, work and life. So it is imperative to develop effective prevention and treatment measures for DAHAS. The present review analyzes effective prophylactic and therapeutic measures against DAHAS, implemented at our hospital.

关键词：治疗高海拔发病率综合征劳动者高原预防

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Over-starvation aggravates intestinal injury and promotes bacterial and endotoxin translocation under high-altitude hypoxic environment

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World Journal of Gastroenterology 2011年第12期17卷 1584-1593页

作者： Qi-Quan Zhou Ding-Zhou Yang Yong-Jun Luo Su-Zhi Li Fu-Yu Liu Guan-Song Wang Department of high altitude Disease College of High Altitude Military MedicineThird Military Medical UniversityChongqing 400038China Key Laboratory of high altitude medicine Ministry of EducationThird Military Medical universityChongqing 400038China Research Center of Mountain Sickness General Hospital of Tibetan Military Area CommandLhasa 850007Tibet Autonomous RegionChina institute of Respiratory Diseases Xinqiao HospitalThird Military Medical UniversityChongqing 400037China

AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic ***:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 *** nitrate was used as a tracer to detect intestinal *** apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling *** levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal *** translocation was detected in blood culture and intestinal *** addition,rats were given Gln intragastrically to observe its protective effect on intestinal ***:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood *** particles were found in the intercellular space and intracellular *** translocation to mesenteric lymph nodes(MLN) and spleen was *** serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(Phigh altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,Phigh-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.

关键词： high altitude Hypoxia Starvation Intestinal mucosal injury Bacterial translocation Endotoxin Glutamine

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FAP senescence:a critical event in muscle regeneration

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2440-2441页

作者： Xia Kang Yuqi Gao So-ichiro Fukada Hongming Miao Department of Pathophysiology College of High Altitude Military MedicineArmy Medical UniversityChongqing400038China Pancreatic Injury and Repair Key Laboratory of Sichuan Province The General Hospital of Western Theater CommandChengduSichuanChina institute of medicine and equipment for high altitude region College of High Altitude Military MedicineThird Military Medical University(Army Medical University)Key Laboratory of Extreme Environmental MedicineMinistry of Education of ChinaKey Laboratory of High Altitude MedicinePeople’s Liberation ArmyChongqing400038China Project for Muscle Stem Cell Biology Graduate School of Pharmaceutical SciencesOsaka UniversitySuitaOsakaJapan Jinfeng Laboratory Chongqing401329China

In a recent study published in Nature,Moiseeva and colleagues examined senescent cells,including fibro/adipogenic progenitors(FAPs),muscle stem cells(MuSCs)and macrophages,which generate an inflammatory and fibrotic niche,thus inhibiting the activation of MuSCs and muscle regeneration.1 The researchers developed a method to distinguish endogenous senescent cells and showed the importance of cellular senescence as a potential target for improving muscle regeneration and repair(Fig.1).^(1)

关键词： endogenous inhibiting critical

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Intermittent Oxygen Inhalation with Proper Frequency Improves Overall Health Conditions and Alleviates Symptoms in a Population at high Risk of Chronic Mountain Sickness with Severe Symptoms

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Chinese Medical Journal 2016年第11期129卷 1322-1329页

作者： Bin Feng Wei-Hao Xu Yu-Qi Gao Fu-Yu Liu Peng Li Shan-Jun Zheng Lu-Yue Gai Gang Zhang Department of Cardiology Chinese People's Liberation Army General Hospital Beijing 100853 China Department of high Altitucle Military Hygiene College of High Altitude Military Medicine Third MilitarY Meclical University Chongqing 400030 China institute of medicine and Hygienic equipment for high altitude region College of High Altitude Military Medicine Third Military Medical University Chongqing 400030 China

Background： Oxygen inhalation therapy is essential for the treatment of patients with chronic mountain sickness （CMS）, but the efficacy of oxygen inhalation for populations at high risk of CMS remains unknown. This research investigated whether oxygen inhalation therapy benefits populations at high risk of CMS. Methods： A total of 296 local residents living at an altitude of 3658 m were included; of which these were 25 diagnosed cases of CMS, 8 cases dropped out of the study, and 263 cases were included in the analysis. The subjects were divided into high-risk （180 ≤ hemoglobin （Hb）〈210 g/L, n = 161） and low-risk （Hb 〈180 g/L, n = 102） groups, and the cases in each group were divided into severe symptom （CMS score ≥6） and mild symptom （CMS score 0-5） subgroups. Severe symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group （A group） or oxygen intake 7 times/week group （D group）; mild symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group （A group）, oxygen intake 2 times/week group （B group）, and 4 times/week group （C group）. The courses for oxygen intake were all 30 days. The CMS symptoms, sleep quality, physiological biomarkers, biochemical markers, etc., were recorded on the day before oxygen intake, on the 15th and 30th days of oxygen intake, and on the 15th day after terminating oxygen intake therapy. Results： A total of 263 residents were finally included in the analysis. Among these high-altitude residents, CMS symptom scores decreased for oxygen inhalation methods B, C, and D at 15 and 30 days after oxygen intake and 15 days after termination, including dyspnea, palpitation, and headache index, compared to those before oxygen intake （B group： Z = 5.604, 5.092, 5.741; C group： Z = 4.155, 4.068, 4.809; D group： Z = 6.021, 6.196, 5.331, at the 3 time points respectively; all P 〈 0.05/3 vs. before intake）. However, dyspnea/palpitation （A group： Z = 5.003, 5.428, 5.493,

关键词： Chronic Mountain Sickness Efficacy Hypoxia Individualized Therapy Oxygen Inhalation

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The substitution of SERCA2 redox cysteine 674 promotes pulmonary vascular remodeling by activating IRE1α/XBP1s pathway

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2315-2329页

作者： Weimin Yu Gang Xu Hui Chen Li Xiao Gang Liu Pingping Hu Siqi Li Vivi Kasim Chunyu Zeng Xiaoyong Tong School of Pharmaceutical Sciences Chongqing UniversityChongqing 401331China institute of Health Biological Chemical Medication Chongqing Institute of Green and Intelligent TechnologyChinese Academy of SciencesChongqing 400714China institute of medicine and equipment for high altitude region College of High Altitude Military MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Key Laboratory of high altitude medicine People’s Liberation ArmyChongqing 400038China Henan Key Laboratory of Medical Tissue Regeneration College of Basic Medical SciencesXinxiang Medical UniversityXinxiang 453003China Key Laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400044China Department of Cardiology Daping HospitalArmy Medical University(Third Military Medical University)Chongqing 400042China

Pulmonary hypertension(PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells(PASMCs)plays an important role. The cysteine 674(C674) in the sarcoplasmic/endoplasmic reticulum Ca^(2+)ATPase 2(SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674 S knock-in mice(SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha(IRE1 a) and spliced X-box binding protein 1(XBP1 s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1 a/XBP1 s pathway inhibitor 4μ8 C. In addition, suppressing the IRE1 a/XBP1 s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2 a, SERCA2 b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1 a/XBP1 s pathway and SERCA2 might be potential targets for PH therapy.

关键词： Pulmonary hypertension Sarcoplasmic/endoplasmic reticulum Ca^(2+)ATPase Pulmonary vascular remodeling Pulmonary artery smooth muscle cell Endoplasmic reticulum stress Oxidative stress

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De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation

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National Science Review 2020年第2期7卷 391-402页

作者： Ouzhuluobu Yaoxi He Haiyi Lou Chaoying Cui Lian Deng Yang Gao Wangshan Zheng Yongbo Guo Xiaoji Wang Zhilin Ning Jun Li Bin Li Caijuan Bai Baimakangzhuo Gonggalanzi Dejiquzong Bianba Duojizhuoma Shiming Liu Tianyi Wu Shuhua Xu Xuebin Qi Bing Su high altitude Medical Research Center School of Medicine Tibetan University Fukang Obstetrics Gynecology and Children Branch Hospital Tibetan Fukang Hospital State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Chinese Academy of Sciences Key Laboratory of Computational Biology CAS-MPG Partner Institute for Computational Biology Shanghai Institute of Nutrition and Health Shanghai Institutes for Biological SciencesUniversity of Chinese Academy of Sciences School of Life Science and Technology Shanghai Tech University Center for Disease Control Tibet Autonomous Region National Key Laboratory of high altitude medicine High Altitude Medical Research Institute Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Collaborative Innovation Center of Genetics and Development

Structural variants(SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome(ZF1), with a contig N50 length of 24.57 mega-base pairs(Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps(0.25 Mb in total length) in the reference human genome(GRCh38). Markedly, we detected17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid(Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1(1.32%–1.53%) compared to other East Asian genomes(0.70%–0.98%),reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence—a662-bp intronic insertion in the SCUBE2 gene—is enriched and associated with better lung function(the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.

关键词： long-read sequencing Tibetan structural variants genetic adaptation reference genome

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high Arterial Oxygen Saturation in the Acclimatized Lowlanders Living at high altitude

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Phenomics 2023年第4期3卷 329-332页

作者： Yaoxi He Chaoying Cui Yongbo Guo Wangshan Zheng Tian Yue Hui Zhang Ouzhuluobu Tianyi Wu Xuebin Qi Bing Su State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China high altitude Medical Research Center School of MedicineTibetan UniversityLhasa 850000China National Key Laboratory of high altitude medicine High Altitude Medical Research InstituteXining 810012China

Blood oxygen saturation(SpO_(2))is a key indicator of oxygen availability in the *** is known that a low SpO_(2)at high altitude is associated with morbidity and mortality risks due to physiological ***,it was proposed that the lowlander immigrants living at high altitude should have a lower SpO_(2)level compared to the highlander natives,but this proposal has not been rigorously tested due to the lack of data from the lowlander immigrants living at high *** this study,we compared arterial oxygen saturation of 5929 Tibetan natives and 1034 Han Chinese immigrants living at altitudes ranging from 1120 m to 5020 ***,the Han immigrants had a higher SpO_(2)than the Tibetan natives at the same high *** the same time,there is a higher prevalence of chronic mountain sickness in Han than in Tibetans at the same *** result suggests that the relatively higher SpO_(2)level of the acclimatized Han is associated with a physiological cost,and the SpO_(2)level of Tibetans tends to be ***,SpO_(2)alone is not a robust indicator of physiological performance at high altitude.

关键词： Oxygen saturation high altitude Acclimatization Adaptation

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A hypothesis study on a four-period prevention model for high altitude disease

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Military Medical Research 2018年第2期5卷 183-188页

作者： Xian-Sheng Liu Xiang-Rong Yang Lu Liu Xian-Kui Qin Yu-Qi Gao institute of medicine and Hygienic equipment for high altitude region College of High Altitude Military MedicineThird Military Medical UniversityNo.30 Gaotanyan StreetShapingba DistrictChongqing 400038China Department of Medical Affairs The 5th Hospital of the Chinese PLANo.893 Shengli StreetXingqing DistrictYinchuanNingxia 750003China Key Laboratory of high altitude Environmental medicine Third Military Medical UniversityMinistry of EducationNo.30 Gaotanyan StreetShapingba DistrictChongqing 400038China Key Laboratory of high altitude medicine of PLA No.30 Gaotanyan StreetShapingba DistrictChongqing 400038China Department of Health Service Training Base of Health ServiceThird Military Medical UniversityNo.30 Gaotanyan StreetShapingba DistrictChongqing 400038China Department of Outpatient PLA No.96819 UnitNo.2 Heping RoadChaoyang DistrictBeijing 100085China

Background:high altitude disease(HAD)can reduce combat effectiveness and damage the health of soldiers at high *** objective of this hypothesis study is to build a four-period prevention model for high altitude disease that can be applied at high altitudes of over 3000 *** of the hypothesis:We divided the time at high altitude into nine periods,with three stages from the ascent preparation to the descent to the plain,and applied a continuous dynamic and systematic four-period prevention model across the nine *** period of three stages has its own different measures and targets high altitude health care services for the prevention of high altitude disease.A standard four-period prevention model for high altitude disease was constructed for the high altitude health services at the population *** the hypothesis:Our hypothesized HAD prevention model represents a continuous dynamic and systematic four-period prevention model across the nine *** hypothesis can be tested from three *** first one is assessment of soldiers’operating *** second is comparison of the long-term high altitude population health basic data and development and utilization of big *** third is descent population health status comparative study and historical retrospective study on ***:As we know,it is necessary to protect soldiers’health through the ascent and *** the standard four-period model,we can protect soldiers’health by preventing high altitude diseases,screening the susceptible population,securely tracking their location and maintaining soldiers’health statuses;we also maintain their operational capabilities,eliminate their psychological fears and ease their family troubles.

关键词： high altitude disease high altitude health service Prevention model

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