Correlation of vascular endothelial growth factor to permeability of blood-brain barrier and brain edema during high-altitude exposure

BACKGROUND： Many studies have evaluated the role of vascular endothelial growth factor （VEGF） in traumatic brain edema and hemorrhagic brain edema. OBJECTIVE： To observe the effects of VEGF expression on permeability of the blood-brain barrier （BBB） during high-altitude and hypoxia exposure, and to investigate the correlation between VEGF expression and BBB permeability with regard to Evans blue staining and brain edema during high-altitude exposure. DESIGN, TIME AND SETTING： The randomized, controlled, animal study was performed at the Tanggula Etape, Central Laboratory of Chengdu Medical College, and Central Laboratory of General Hospital of Chengdu Military Area Command of Chinese PLA, China, from July 2003 to November 2004. MATERIALS： Quantitative RT-PCR kit （Sigma, USA）, VEGF ELISA kit （Biosource, USA）, and Evans blue （Jingchun, China） were acquired for this study. METHODS： A total of 180 Wistar rats were equally and randomly assigned to 15 groups： low-altitude （500 m）, middle-altitude （2 880 m）, high-altitude （4 200 m）, super-high-altitude （5 000 m）, 1,3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days of super high-altitude exposure. Wistar rats were exposed to various altitude gradients to establish a hypoxia model. MAIN OUTCOME MEASURES： Brain water content was calculated according to the wet-to-dry weight ratio. BBB permeability to Evans blue was determined by colorimetric method. VEGF mRNA and protein levels in brain tissues were detected using RT-PCR and double-antibody sandwich ELISA. RESULTS： Brain water content, BBB permeability to Evans blue, and VEGF mRNA and protein levels in brain tissues increased with increasing altitude and prolonged exposure to altitude. The greatest increase was determined on day 9 upon ascending 5 000 m. Simultaneously, VEGF expression positively correlated to BBB permeability of Evans blue and brain water content （r = 0.975, 0.917, P〈 0.01）. CONCLUSION： Increased VEGF protein and mRNA expression was responsible for increased BBB permeability, which may be an important mechanism underlying brain edema during high-altitude exposure.

Regular Observation of De-Acclimatization and Randomized Controlled Research of Diagnostic Criteria of High Altitude De-Acclimatization Syndrome among Different Plateau Migrants Crowd after Their Return to the Plain

Objective: The objective of this study was to investigate the diagnostic methods of high altitude de-acclimatization syndrome and to formulate diagnostic criteria. Methods: This study was conducted using epidemiological surveys and a multi-center randomized controlled clinical trial. A total of 3011 subjects were studied, and the following indices were collected after their return to low altitude areas from the plateau: general health status, blood, urine and stool samples, myo-cardial enzyme levels, liver and kidney function, nerve function, sex hormone levels, microalbuminuria, electrocardiogram (ECG), echocardiography, pulmonary function, and hemorheological markers. These data were compared to those of randomized healthy subjects in the same age range who lived at the same altitude to determine the characteristics of high altitude de-acclimatization syndrome. Based on these characteristics, diagnostic criteria for high altitude de-acclimatization syndrome were formulated. Results: This study demonstrated that the incidence of high altitude de-acclimatization syndrome was 84.36%. Sixty percent of the cases were mild, 30% were medium, and 10% were severe. The incidence was higher among those who returned to a place of lower altitude, resided at a high altitude for a longer period of time, or engaged in heavy labor while at high altitude. Patients with high altitude de-acclimatization syndrome manifested hematological abnormalities and abnormal ventricular function, notably a right ventricular diastolic function, which recovered to baseline function after one to five years. Exposure to long-term hypoxia often caused obvious changes in cardiac morphology, i.e., left and right ventricular hypertrophy, particularly within the right ventricle. In addition, patients with high altitude de-acclimatization syndrome often presented with low blood pressure, low pulse pressure, and microalbuminuria. A few patients presented with occult blood in their feces. The diagnosis of high altitude de-acclimatization syndrome can be made if a patient who recently returns to the plain from the plateau complains of dizziness, weakness, sleepiness, chest tightness, edema, memory loss, and other symptoms and signs that do not alleviate under short-term rehabilitation or symptomatic treatment, and if organic diseases of the heart, lung, kidney, and other organs have been excluded. Conclusion: The diagnosis of high altitude de-acclimatization syndrome should be made after a comprehensive analysis of the patient’s clinical symptoms and signs.

Pathophysiological changes in mitochondria of mammalian exposed to hypoxia at high altitude

As human beings ascend to high altitude,a number of reactions may occur against hypoxic injuries.These hypoxic responses are related to intake,transportation and utility of the oxygen.As a crucial subcellular organelle of oxygen utility,mitochondrion is a central link of high altitude acclimatization,adaptation and mountain sicknesses.In this review,we discussed the recent advances in researches on hypoxic mitochondrial responses at high altitude.

Diagnostic criteria of high altitude de-acclimatization syndrome among plateau migrants after their return to the plain: a multi-center randomized controlled trial

Objective: The objective of this study was to investigate the diagnostic methods of high altitude de-acclimatization syndrome and to formulate diagnostic criteria.Methods: This study was conducted using epidemiological surveys and a multi-center randomized controlled clinical trial. A total of 3,011 subjects were studied, and the following indices were collected after their return to low altitude areas from the plateau: general health status, blood, urine and stool samples, myocardial enzyme levels, liver and kidney function, nerve function, sex hormone levels, microalbuminuria, electrocardiogram(ECG), echocardiography, pulmonary function, and hemorheological markers. These data were compared to those of randomized healthy subjects in the same age range who lived at the same altitude to determine the characteristics of high altitude deacclimatization syndrome. Based on these characteristics, diagnostic criteria for high altitude de-acclimatization syndrome were formulated.Results: This study demonstrated that the incidence of high altitude de-acclimatization syndrome was 84.36%. Sixty percent of the cases were mild, 30% were medium, and 10% were severe. The incidence was higher among those who returned to a place of lower altitude, resided at a high altitude for a longer period of time, or engaged in heavy labor while at high altitude. Patients with high altitude de-acclimatization syndrome manifested hematological abnormalities and abnormal ventricular function, notably a right ventricular diastolic function, which recovered to baseline function after one to five years. Exposure to long-term hypoxia often caused obvious changes in cardiac morphology, i.e., left and right ventricular hypertrophy, particularly within the right ventricle. In addition, patients with high altitude de-acclimatization syndrome often presented with low blood pressure, low pulse pressure, and microalbuminuria. A few patients presented with occult blood in their feces. The diagnosis of high altitude deacclimatization syndrome can be made if a patient who recently returns to the plain from the plateau complains of dizziness, weakness, sleepiness, chest tightness, edema, memory loss, and other symptoms and signs that do not alleviate under short-term rehabilitation or symptomatic treatment, and if organic diseases of the heart, lung, kidney, and other organs have been excluded.Conclusion: The diagnosis of high altitude de-acclimatization syndrome should be made after a comprehensive analysis of the patient's clinical symptoms and signs.

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

AIM:To study whether over-starvation aggravates intestinal mucosal injury and promotes bacterial and endotoxin translocation in a high-altitude hypoxic environment.METHODS:Sprague-Dawley rats were exposed to hy-pobaric hypoxia at a simulated altitude of 7000 m for 72 h.Lanthanum nitrate was used as a tracer to detect intestinal injury.Epithelial apoptosis was observed with terminal deoxynucleotidyl transferase dUTP nick end labeling staining.Serum levels of diamino oxidase(DAO),malondialdehyde(MDA),glutamine(Gln),superoxide dismutase(SOD) and endotoxin were measured in intestinal mucosa.Bacterial translocation was detected in blood culture and intestinal homogenates.In addition,rats were given Gln intragastrically to observe its protective effect on intestinal injury.RESULTS:Apoptotic epithelial cells,exfoliated villi and inflammatory cells in intestine were increased with edema in the lamina propria accompanying effusion of red blood cells.Lanthanum particles were found in the intercellular space and intracellular compartment.Bacterial translocation to mesenteric lymph nodes(MLN) and spleen was evident.The serum endotoxin,DAO and MDA levels were significantly higher while the serum SOD,DAO and Gln levels were lower in intestine(P< 0.05).The bacterial translocation number was lower in the high altitude hypoxic group than in the high altitude starvation group(0.47±0.83 vs 2.38±1.45,P<0.05).The bacterial translocation was found in each organ,especially in MLN and spleen but not in peripheral blood.The bacterial and endotoxin translocations were both markedly improved in rats after treatment with Gln.CONCLUSION:High-altitude hypoxia and starvation cause severe intestinal mucosal injury and increase bacterial and endotoxin translocation,which can be treated with Gln.

Therapeutic intervention against deacclimatization to high altitude

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.

Association between endothelial nitric oxide synthase(ENOS) G894T polymorphism and high altitude(HA) adaptation： a meta-analysis

Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthase(ENOS) G894 T polymorphism contributed to the physiology and pathophysiology of humans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894 T polymorphism and HA adaptation through analyzing the published data. Methods: We searched all relevant literature about the ENOS G894 T polymorphism and HA adaptation in Pub Med, Medline, and Embase before Step 2015. A random-effects model was applied(Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. Results: From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups(OR=1.85; 95% CI, 1.47–2.33; P<0.0001). In addition, the GG genotype was significantly associated with HA adaptation(OR=1.99; 95% CI, 1.54–2.57; P<0.0001). Conclusion: Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.

Relationship between acute high altitude response, cardiac function injury, and high altitude de-adaptation response after returning to lower altitude

The relationship between acute high altitude response (AHAR), cardiac function injury, and high altitude de-adaptation response (HADAR) was assessed. Cardiac function indicators were assessed for 96 men (18 - 35 years old) deployed into a high altitude (3700 - 4800 m) environment requiring intense physical activity. The subjects were divided into 3 groups based on AHAR at high altitude: severe AHAR (n = 24), mild to moderate AHAR (Group B, n = 47) and non-AHAR (Group C, 25);and based on HADAR: severe HADAR (Group E, n = 19), mild to moderate HADAR (Group F, n = 40) and non-HADAR (Group G, n = 37) after return to lower altitude (1,500 m). Cardiac function indicators were measured after 50 days at high altitude and at 12 h, 15 days, and 30 days after return to lower altitude. Controls were 50 healthy volunteers (Group D, n = 50) at 1500 m. Significant differences were observed in cardiac function indicators among groups A, B, C, and D. AHAR score was positively correlated with HADAR score (r = 0.863, P < 0.001). Significant differ- ences were also observed in cardiac function indicators among groups D, E, F, and G, 12 h and15 days after return to lower altitude. There were no significant differences in cardiac function indicators among the groups, 30 days after return to lower altitude, compared to group D. The results indicated that the severity of HADAR is associated with the severity of AHAR and cardiac injury, and prolonged recovery.

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

Background:High altitude disease(HAD)can reduce combat effectiveness and damage the health of soldiers at high altitudes.The 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 m.Presentation 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 periods.Each 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 level.Testing the hypothesis:Our hypothesized HAD prevention model represents a continuous dynamic and systematic four-period prevention model across the nine periods.This hypothesis can be tested from three aspects.The first one is assessment of soldiers’operating efficacies.The second is comparison of the long-term high altitude population health basic data and development and utilization of big data.The third is descent population health status comparative study and historical retrospective study on prevention.Implications:As we know,it is necessary to protect soldiers’health through the ascent and descent.Through 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.

Observetion of major organs deadaptation change after returning to lower altitude in Qinghai-Tibet railway construction population

High altitude deadaptation affects the health of population returned to the plain. We examined major physiological functions in 348 healthy control subjects and 626 Qinghai-Tibet railway construction workers who returned to the plain from the Qinghai-Tibet plateau. Blood indices, such as hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration and platelet larger cell ratio, of the returned group that had stayed at high altitude more than 3 years were significantly higher than those of the control group. Red blood cell distribution width and platelet were significantly lower in the returned group than in the control group. Compared to the control group, five years after returning to the plain, the returned group had higher mean corpuscular hemoglobin and lower red blood cell distribution width. Detection rate of hypotension and low pulse pressure were significantly higher in the returned group than in the control group at 20 months after the return, and cardiothoracic ratio was significantly higher in the returned group than in the control group at 40 months after the return. Short-term memory function was significantly lower in the returned group than in the control group. Total triiodothyronine and thyroid-stimulating hormone were significantly lower, but total thyroxine and free triiodothyronine were significantly higher in the returned group than in the control group. Sex hormones level returned to normal level in the returned group. Superoxide dismutase was significantly higher and malondialdehyde was significantly lower in the returned group than in the control group. Fatty acid binding protein was significantly higher in the returned group than in the control group, and this difference maintained with time after the return. We conclude that physiological functions of most organs in returned population after exposed to high altitude can not be completely restored to the normal level in a short period of time.

Altered expression of mitochondrial related genes in the native Tibetan placents by mitochondrial cDNA array analysis

Objective： To explore the mechanism of native Tibetan fetuses adaptation to hypoxia, we tried to find the different expression genes about mitochondrial function in the native Tibetan placents. Methods： In this study, the placents of native Tibetan and the high-altitude Hart （ha-Hart） were collected. After the total RNA extraction, the finally synthesized cDNAs were hybridized to mitochondrial array to find the altered expression genes between them. Then, the cytochrome c oxidase 17 （Coxl7）, dynactin 2 （DCTN2, also known as p50）, and vascular endothelial growth factor receptor （VEGFR, also known as KDR） were chosen from the altered expression genes to further verify the array results using the SYBR Green real-time PCR. Because the altered expression genes （such as Cybb and Cox 17） in the array results related to the activities of COXI and COXIV, the placental mitochondria activities of COXI and COXIV were measured to find their changes in the hypoxia. Results： By a standard of≥1.5 or ≤0.67, there were 24 different expressed genes between the native Tibetan and the ha-Han placents, including 3 up-regulated genes and 21 down-regulated genes. These genes were related to energy metabolism, signal transduction, cell proliferation, electron transport, cell adhesion, nucleotide-excision repair. The array results of Cox17, DCTN2 and KDR were further verified by the real-time RT-PCR. Through the mitochondria respiration measurements, the activity of COXI in the native Tibetan placents were higher than that of ha-Han, there was no difference in COXIV activity between them. Conclusion： The altered mitochondrial related genes in the native Tibetan placents may have a role in the high altitude adaptation for fetuses through changing the activity of mitochondrial COX.

Association of iodized salt with goiter prevalence in Chinese populations: a continuity analysis over time

Background: Iodine deficiency disorders(IDD) refer to diseases that are caused by insufficient iodine intake, and the best strategy to prevent IDD is the addition of iodine to dietary salt. Because iodine deficiency is a common cause of goiter, the prevalence as effectively controlled after the implementation of universal salt iodization(USI) in China. However, there is substantial controversy as to whether the incidence of thyroid disorders is related to iodized salt intake. Therefore, we aimed to clarify whether the risk of goiter can be promoted by USI.Methods: A longitudinal continuous study based on the national monitoring results of IDD in China was performed for 3 consecutive years. We recorded the following indicators of IDD from 31 provinces: goiter number, two degrees of goiter(the degree of goiter severity) and cretinism(three endemic diseases), iodized salt intake, median urinary iodine concentration(UIC), soil iodine content and coverage rates of iodized salt. One-way Analysis of Variance(ANOVA) and linear regression analyses examined the differences between the three groups and correlations, respectively. Data were collected from the Chinese national IDD surveillance data in 2011-2013, and the background values of Chinese soil elements were published in 1990.Results: A reference male's daily intake of maximum iodine was 378.9μg, 379.2μg and 366.9μg in 2011, 2012, and 2013, respectively. No statistical association between daily iodized salt intake and the three endemic diseases was observed in 2011-2013(P >0.05). No association was observed between daily iodized salt intake and the UIC of children in 2011(P>0.05). Linear regression revealed no significant correlation between the soil iodine content and three endemic diseases. The present study indicated no difference in the daily iodized salt intake in each province during three years(F=0.886, P=0.647). The coverage rate of iodized salt remained above 98.7%, and goiter rates were stable in 2011-2013.Conclusion: There was no significant association between iodized salt intake and the three endemic diseases, suggesting that the current nutrition level of iodized salt did not cause the high goiter prevalence.

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

Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.Methods: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 determined.Then,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 functions.The 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 function.ATP 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 performed.Results:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability.The 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 group.NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia.Moreover,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia.Furthermore,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 hypoxia.Additionally,ATP levels in the gastrocnemius muscle significantly increased,while lactate levels in sera significantly decreased.Conclusion:NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.

Characteristics of fat metabolism in skeletal muscle of rats after hypobaric hypoxic acclimation

Objective：To investigate the characteristics of fat metabolism in rat skeletal muscle after hypobaric hypoxia acclimation. Methods： Sprague-Dawley rats were divided into 3 groups randomly： control group （H0）, hypoxic 5-day group （HS）, and hypoxic 15-day group （H15）. Animals of H5 and 15 groups were exposed to hypobaric hypoxia chamber simulating 5 000 m high altitude for 5 d or 15 d respectively, 23 h per day. H0 group stayed outside of chamber The level of fatty acid oxidation and uptake, and glucose oxidation were examined, and the level of non-esterified fatty acids （NEFA）, ATP and phosphocreatine （PCr） were also assayed in rat skeletal muscles. Results： The contents of ATP and PCr in H5 group were lower than those in H0 and H15 groups （P〈0.05）, while there was no significant difference between H0 and H15. Compared with H0, the blood NEFA level in all hypoxia groups was increased significantly （P〈0.05）. The muscle NEFA level in H15 group was greatly higher than that in H0 and H5 groups. The rates of fatty acid oxidation and uptake in H15 group were significantly higher than those in H0 and H5 groups （P〈0.05）, and the rate of glucose oxidation in all hypoxia groups was significantly decreased than that in H0 group （P〈0.05）. Conclusion： It is concluded that the enhanced fat oxidation may be one of the mechanisms in the maintenance of energy homeostasis after hypobaric hypoxic acclimation.

Effects of Chinese herbal monomers on oxidative phosphorylation and membrane potential in cerebral mitochondria isolated from hypoxia-exposed rats in vitro

Mitochondrial dysfunction is the key pathogenic mechanism of cerebral injury induced by high-altitude hypoxia. Some Chinese herbal monomers may exert anti-hypoxic effects through enhancing the efficiency of oxidative phosphorylation, in this study, effects of 10 kinds of Chinese herbal monomers on mitochondrial respiration and membrane potential of cerebral mitochondria isolated from hypoxia-exposed rats in vitro were investigated to screen anti-hypoxic drugs. Rats were exposed to a low-pressure environment of 405.35 mm Hg （54.04 kPa） for 3 days to establish high-altitude hypoxic models. Cerebral mitochondria were isolated and treated with different concentrations of Chinese herbal monomers （sinomenine, silymarin, glycyrrhizic acid, baicalin, quercetin, ginkgolide B, saffron, pipedne, ginsenoside Rgl and oxymatrine） for 5 minutes in vitro. Mitochondrial oxygen consumption and membrane potential were measured using a Clark oxygen electrode and the rhodamine 123 fluorescence analysis method, respectively. Hypoxic exposure significantly decreased the state 3 respiratory rate, respiratory control rate and mitochondrial membrane potential, and significantly increased the state 4 respiratory rate. Treatment with saffron ginsenoside Rgl and oxymatrine increased the respiratory control rate in cerebral mitochondria isolated from hypoxia-exposed rats in dose-dependent manners in vitro, while ginsenoside Rgl, piperine and oxymatrine significantly increased the mitochondrial membrane potential in cerebral mitochondria from hypoxia-exposed rats. The Chinese herbal monomers saffron, ginsenoside Rgl piperine and oxymatrine could thus improve cerebral mitochondrial disorders in oxidative phosphorylation induced by hypobaric hypoxia exposure in vitro.

Role of medical resource level in iodine deficiency disorder

Background:Iodine deficiency disorders(IDDs)refer to a series of diseases caused by the human body's insufficient iodine intake.Edible salt became iodized in China in 1996,which yielded remarkable results.We have known that IDDs is associated with iodine in the human body,but it is not clear whether IDDs is related to medical resource level.Methods:We collected the number of IDDs cases and an index for the level of medical resource from 31 provinces,autonomous regions and municipalities directly under the central government in China.All data came from the China Statistical Yearbook of Health and Family Planning issued in 2013 by the Peking Union Medical College Publishing House.Data standardization and linear regression analysis were used.Results:The results showed that IDDs correlated with the number of beds in medical and health institutions,number of medical health personnel,number of medical and health institutions,total health expenditure,average health expenditure per capita,medical insurance for urban resident and new rural cooperative medical rural residents(P<0.01).In a multiple linear regression,IDDs was most significantly associated with the number of beds in hospitals,the number of rural health personnel,the number of basic medical and health institutions and government health expenditure for these institutions. Conclusion:Based on the experimental data,we concluded that IDDs had a positive connection with the medical resource level,and basic and rural areas had a more significant association with IDDs.This analysis provides new and explicit ideas for iodine prevention and control work in China.

Altofrequency SNPs of mitochondrial DNA in 26 Han Chinese

Objective: To explore the possible mitochondrial DNA (mtDNA) polymorphism in Han Chinese. Methods: The complete mitochondrial genome of 26 unrelated healthy Han Chinese were extracted and sequenced. Results:The mtDNA nucleotide sites (2 706, 7 028, 8 860, 11 719, and 15 326) were found totally different from the Revised Cambridge Reference Sequence (rCRS). These single nucleotide polymorphisms (SNPs) were 2 706 A→G, 7 028 C→T, 8 860 A→G, 11 719 G→A, 15 326 A→G. Conclusion: These findings provide new insights into the characteristics of Han Chinese mitochondrial genetic diversity.

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

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, both P 〈 0.05/3 vs. before intake） and headache （A group： Z = 4.263, 3.890, 4.040, both P 〈 0.05/3 vs. before intake） index decreased significantly also for oxygen inhalation method A at all the 3 time points. Cyanosis index decreased significantly 30 days after oxygen intake only in the group of participants administered the D method （Z= 2.701, P = 0.007）. Tinnitus index decreased significantly in group A and D at 15 days （A group： Z = 3.377, P = 0.001, D group： Z = 3.150, P - 0.002）, 30 days after oxygen intake （A group： Z = 2.836, P = 0.005, D group： Z = 5.963, P 〈 0.0001） and 15 days after termination （A group： Z- 2.734, P = 0.006, D group： Z - 4.049, P = 0.0001）, and decreased significantly in the group B and C at 15 days after termination （B group： Z = 2.611, P = 0.009; C group： Z = 3.302, P = 0.001）. In the population at high risk of CMS with severe symptoms, oxygen intake 7 times/weeksignificantly improved total symptom scores of severe symptoms at 15 days （4 [2, 5] vs. 5.5 [4, 7], Z = 2.890, P = 0.005） and 30 days （3 [1, 5] vs. 5.5 [2, 7], Z= 3.270, P = 0.001） after oxygen intake compared to no oxygen intake. In the population at high risk of CMS with mild symptoms, compared to no oxygen intake, oxygen intake 2 or 4 times/week did not improve the total symptom scores at 15 days （2 [1, 3], 3 [1, 4] vs. 3 [1.5, 5]; 2＂2 = 2.490, P= 0.288）, and at 30 days （2 [0, 4], 2 [1, 4.5] vs. 3 [2, 5];2＂2- 3.730, P = 0.155） after oxygen intake. In the population at low risk ofCMS, oxygen intake did not significantly change the white cell count and red cell count compared to no oxygen intake, neither in the severe symptomatic population nor in the mild symptomatic population. Conclusions： Intermittent oxygen inhalation with proper frequency might alleviate symptoms in residents at high altitude by improving their overall health conditions. Administration of oxygen inhalation therapy 2-4 times/week might not benefit populations at high risk of CMS with mild CMS symptoms while administration of therapy 7 times/week might benefit those with severe symptoms. Oxygen inhalation therapy is not recommended for low-risk CMS populations.

Changes in oxygen saturation can not help diagnose acute mountain sickness(AMS)： ascending to Lhasa on the Qinghai-Tibet train

Objective: Acute mountain sickness(AMS) is a common condition in individuals who ascend to altitudes over 2 500 m. There is no measurements that can reliably predict or diagnose this condition. We therefore determined whether pulse oximetry data are associated with the development of AMS and can help diagnose AMS. Methods: We studied 58 young male undergraduates who traveled from Chongqing(300 m) to Lhasa(3 658 m) by train. We collected data on the ascent profiles and AMS symptoms based on the Lake Louise Score(LLS). The resting arterial oxygen saturation(R-Sp O2) and pulse rate were then measured using finger pulse oximetry. Results: In Golmud(2 800 m) and Tanggula(5 200 m), R-SpO_2 was significantly lower in the AMS group than in the group without AMS(P<0.05). However, upon arrival in Lhasa(3 658 m), the R-SpO_2 was higher in the AMS group than in the non-AMS group(P<0.05). In Tanggula, the change in the SpO_2(CR-SpO_2) in the AMS group was higher than that in the non-AMS group(P<0.05). But in Lhasa, the CR-SpO_2 in the AMS group was lower than that in the non-AMS group(P<0.05). We also monitored heart rate(HR) throughout the study. In Xining(2 200 m) and Golmud, the HRs in the AMS group were higher than those in the non-AMS group. However, the HRs in the AMS group were lower than those in the non-AMS group in Tanggula and Lhasa. Conclusion: Based on the results of this study, the R-SpO_2 graph was not consistent. We can thus conclude that the utility of SpO_2 remains limited in the diagnosis of AMS. The results suggest that using pulse oximetry to diagnose AMS is not valuable in people ascending to Lhasa on the Qinghai-Tibet train.

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

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 tolerance.Methods: 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, respectively.Results: 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 method.Conclusions: ASTT could be a better index than STT for the evaluation of hypoxia tolerance abilities as it could eliminate the impact of animal BW.