Tibetans are well adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene(GCH1, GTP-cyclo...Tibetans are well adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene(GCH1, GTP-cyclohydrolase I), involved in maintaining nitric oxide synthetase(NOS) function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans. Combined with previously published data, we demonstrated many GCH1 variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation, and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.展开更多
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 ...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.展开更多
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 epidemiologic...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.展开更多
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-pobari...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.展开更多
The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene...The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300(histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide(NO) concentration. Col ectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.展开更多
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...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.展开更多
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 synthas...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.展开更多
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 altit...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.展开更多
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 retur...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.展开更多
AIM:To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley,China,to provide a reference for treatment and prevention of regional gastric cancer.METHODS:Between February 200...AIM:To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley,China,to provide a reference for treatment and prevention of regional gastric cancer.METHODS:Between February 2003 and February2013,the records of 2419 patients with gastric cancer were included in this study.The patient’s characteristics,histological and pathological features,as well as the dietary habits of the patients,were investigated.RESULTS:The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area.Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50years group showed the high incidence of gastric cancer in all ethnic groups.There were more male gastric cancer patients than female.Intestinal was the most common type of gastric cancer in the Hehuang valley.There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection.The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food,consumption of high-salt,high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females.CONCLUSION:Differences existed in race,sex,and age of patients according to the epidemiology of gastric cancer in the Hehuang valley.Moreover,dietary habits was also an important factor contributing to gastric cancer.展开更多
Mean hemoglobin(Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders(Tibetans, Sherpas, and Ladakhis) was compared with lowlanders(Chinese Han, Indian Tamils) lived in the Himalay...Mean hemoglobin(Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders(Tibetans, Sherpas, and Ladakhis) was compared with lowlanders(Chinese Han, Indian Tamils) lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness(CMS). Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.展开更多
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,...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 Han (ha-Han) 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 (Cox17), 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 Cox17) 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.展开更多
Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily us...Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.展开更多
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 i...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.展开更多
Background: People rapidly ascending to high altitudes(>2500m) may suffer from acute mountain sickness(AMS). The association between smoking and AMS risk remains unclear. Therefore, we performed a meta-analysis to ...Background: People rapidly ascending to high altitudes(>2500m) may suffer from acute mountain sickness(AMS). The association between smoking and AMS risk remains unclear. Therefore, we performed a meta-analysis to evaluate the association between smoking and AMS risk.Methods: The association between smoking and AMS risk was determined according to predefined criteria established by our team. Meta-analysis was conducted according to the PRISMA guidelines. We included all relevant studies listed in the Pub Med and Embase databases as of September 2015 in this meta-analysis and performed systemic searches using the terms "smoking", "acute mountain sickness" and "risk factor". The included studies were required to provide clear explanations regarding their definitions of smoking, the final altitudes reached by their participants and the diagnostic criteria used to diagnose AMS. Odds ratios(ORs) were used to evaluate the association between smoking and AMS risk across the studies, and the Q statistic was used to test OR heterogeneity, which was considered significant when P<0.05. We also computed 95% confidence intervals(CIs). Data extracted from the articles were analyzed with Review Manager 5.3(Cochrane Collaboration, Oxford, UK).Results: We used seven case-control studies including 694 smoking patients and 1986 non-smoking controls to analyze the association between smoking and AMS risk. We observed a significant association between AMS and smoking(OR=0.71, 95% CI 0.52–0.96, P=0.03).Conclusion: We determined that smoking may protect against AMS development. However, we do not advise smoking to prevent AMS. More studies are necessary to confirm the role of smoking in AMS risk.展开更多
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 ...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, piperine, ginsenoside Rg1 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 Rg1 and oxymatrine increased the respiratory control rate in cerebral mitochondria isolated from hypoxia-exposed rats in dose-dependent manners in vitro, while ginsenoside Rg1, piperine and oxymatrine significantly increased the mitochondrial membrane potential in cerebral mitochondria from hypoxia-exposed rats. The Chinese herbal monomers saffron, ginsenoside Rg1, piperine and oxymatrine could thus improve cerebral mitochondrial disorders in oxidative phosphorylation induced by hypobaric hypoxia exposure in vitro.展开更多
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.T...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.展开更多
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 ...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.展开更多
Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial License(http:1/creativecommons.org/licenses/by-nc/4.0/).which permits unrestrictednon-commercial...Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial License(http:1/creativecommons.org/licenses/by-nc/4.0/).which permits unrestrictednon-commercial use,distribution.and reproduction in any medium.展开更多
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou.,31501013 to HZ and 31360032 to CC)+2 种基金the National 973 program(2012CB518202 to TW)the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04)the Zhufeng Scholar Program of Tibetan University
文摘Tibetans are well adapted to high-altitude hypoxia. Previous genome-wide scans have reported many candidate genes for this adaptation, but only a few have been studied. Here we report on a hypoxia gene(GCH1, GTP-cyclohydrolase I), involved in maintaining nitric oxide synthetase(NOS) function and normal blood pressure, that harbors many potentially adaptive variants in Tibetans. We resequenced an 80.8 kb fragment covering the entire gene region of GCH1 in 50 unrelated Tibetans. Combined with previously published data, we demonstrated many GCH1 variants showing deep divergence between highlander Tibetans and lowlander Han Chinese. Neutrality tests confirmed a signal of positive Darwinian selection on GCH1 in Tibetans. Moreover, association analysis indicated that the Tibetan version of GCH1 was significantly associated with multiple physiological traits in Tibetans, including blood nitric oxide concentration, blood oxygen saturation, and hemoglobin concentration. Taken together, we propose that GCH1 plays a role in the genetic adaptation of Tibetans to high altitude hypoxia.
基金Supported by:the Tackle Key Problem in Science and Technology during the "11~(th) Five-Year Plan" Period of Chinese PLA,No.06G030
文摘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.
文摘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.
基金Supported by Scientific and Technical Research Funds from Chinese PLA during the Eleventh Five-Year Plan Period,No. 2008G093National Natural Science Foundation of China,No. 30900715National Science and Technology Ministry,No. 2009BAI85B03
文摘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.
基金supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13010000)the National Natural Science Foundation of China(91631306 to BS,31671329 to XQ,31460287 to Ou,31501013 to HZ,and 31360032 to CC)+2 种基金the National 973 program(2012CB518202 to TW)the State Key Laboratory of Genetic Resources and Evolution(GREKF15-05,GREKF16-04)the Zhufeng Scholar Program of Tibetan University
文摘The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300(histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide(NO) concentration. Col ectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.
文摘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.
基金supported by the National Natural Science Foundation of China(81372125)
文摘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.
基金supported by the National Basic Research and Development Program of China(973 Program)(2012CB518201)the“13th Five-Year Plan”Medical Science Development Foundation of PLA(AWS14C007)the Basic Scientific Personnel Training Foundation of China(J1310001).
文摘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.
文摘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.
基金Supported by Basic Research Foundation of Qinghai Province,No.2011-Z-730
文摘AIM:To investigate the clinical epidemiological characteristics of gastric cancer in the Hehuang valley,China,to provide a reference for treatment and prevention of regional gastric cancer.METHODS:Between February 2003 and February2013,the records of 2419 patients with gastric cancer were included in this study.The patient’s characteristics,histological and pathological features,as well as the dietary habits of the patients,were investigated.RESULTS:The clinical data showed that adenocarcinoma was the leading histological type of gastric cancer in this area.Characteristics of gastric cancer in different ethnic groups and age showed that the 60.55-65.50years group showed the high incidence of gastric cancer in all ethnic groups.There were more male gastric cancer patients than female.Intestinal was the most common type of gastric cancer in the Hehuang valley.There was no significant difference in the proportion of sex in terms of Helicobacter pylori infection.The impact of dietary habits on gastric cancer showed that regular consumption of fried or grilled food,consumption of high-salt,high-fat and spicy food and drinking strong Boiled brick-tea were three important factors associated with gastric cancer in males and females.CONCLUSION:Differences existed in race,sex,and age of patients according to the epidemiology of gastric cancer in the Hehuang valley.Moreover,dietary habits was also an important factor contributing to gastric cancer.
基金supported by the"973"National Basic Research Program(2012 CB 518202,and"Pre-973"National Basic Research Program(2012 CB 722506),PRC
文摘Mean hemoglobin(Hb) concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders(Tibetans, Sherpas, and Ladakhis) was compared with lowlanders(Chinese Han, Indian Tamils) lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness(CMS). Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.
基金Supported by the National Basic Research Program of China (973 Program, 2006CB504101)the National Natural Science Foundation of China (30393131)
文摘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 Han (ha-Han) 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 (Cox17), 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 Cox17) 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.
基金supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)+6 种基金Lundbeck Foundation Grant(R190-2014-2827)Carlsberg Foundation Grant(CF16-0663)to G.J.Z.Science and Technology Program of Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Project in Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for “Significant New Drugs Development”(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G
文摘Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.
基金supported by the National Natural Science Foundation of China(No.81372125)
文摘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.
基金supported by the National Natural Science Foundation of China(No.81372125)
文摘Background: People rapidly ascending to high altitudes(>2500m) may suffer from acute mountain sickness(AMS). The association between smoking and AMS risk remains unclear. Therefore, we performed a meta-analysis to evaluate the association between smoking and AMS risk.Methods: The association between smoking and AMS risk was determined according to predefined criteria established by our team. Meta-analysis was conducted according to the PRISMA guidelines. We included all relevant studies listed in the Pub Med and Embase databases as of September 2015 in this meta-analysis and performed systemic searches using the terms "smoking", "acute mountain sickness" and "risk factor". The included studies were required to provide clear explanations regarding their definitions of smoking, the final altitudes reached by their participants and the diagnostic criteria used to diagnose AMS. Odds ratios(ORs) were used to evaluate the association between smoking and AMS risk across the studies, and the Q statistic was used to test OR heterogeneity, which was considered significant when P<0.05. We also computed 95% confidence intervals(CIs). Data extracted from the articles were analyzed with Review Manager 5.3(Cochrane Collaboration, Oxford, UK).Results: We used seven case-control studies including 694 smoking patients and 1986 non-smoking controls to analyze the association between smoking and AMS risk. We observed a significant association between AMS and smoking(OR=0.71, 95% CI 0.52–0.96, P=0.03).Conclusion: We determined that smoking may protect against AMS development. However, we do not advise smoking to prevent AMS. More studies are necessary to confirm the role of smoking in AMS risk.
基金supported by the Natural Science Foundation of China,No.81171875
文摘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, piperine, ginsenoside Rg1 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 Rg1 and oxymatrine increased the respiratory control rate in cerebral mitochondria isolated from hypoxia-exposed rats in dose-dependent manners in vitro, while ginsenoside Rg1, piperine and oxymatrine significantly increased the mitochondrial membrane potential in cerebral mitochondria from hypoxia-exposed rats. The Chinese herbal monomers saffron, ginsenoside Rg1, piperine and oxymatrine could thus improve cerebral mitochondrial disorders in oxidative phosphorylation induced by hypobaric hypoxia exposure in vitro.
基金supported by grants from the National Science and Technology Major Project(2014ZX09J14102-05B and 2018ZX09J18109)。
文摘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.
基金supported by the National Natural Science Foundation of China(No.81372125)
文摘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.
基金This study was supported by the National Natural Science Foundation of China(81773711)to W.Y.Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000)to G.J.Z.+4 种基金Science and Technology Programof Guangzhou,China(201704020103)to W.Y.Introduction of Innovative R&D Team Program of Guangdong Province(2013Y104)Leading Talent Projectin Science and Technology of Guangzhou Development District(2019-L002)National Major Scientific and Technological Special Project for"Significant New Drugs Development"(2016ZX09101026)to S.Z.L.Key Projects of the Military Science and Technology PLA(AWS14C007 and AWS16J023)to Y.Q.G.
文摘Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial License(http:1/creativecommons.org/licenses/by-nc/4.0/).which permits unrestrictednon-commercial use,distribution.and reproduction in any medium.
