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| 1 | GCH1 plays a role in the high-altitude adaptation of Tibetans显示文摘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. | Yong-Bo Guo Yao-Xi He Chao-Ying Cui Ouzhuluobu Baimakangzhuo Duojizhuoma Dejiquzong Bianba Yi Peng Cai-juan Bai Gonggalanzi Yong-Yue Pan Qula Kangmin Cirenyangji Baimayangji Wei Guo Yangla Hui Zhang Xiao-Ming Zhang Wang-Shan Zheng Shu-Hua Xu Hua Chen Sheng-Guo Zhao Yuan Cai Shi-Ming Liu Tian-Yi Wu Xue-Bin Qi Bing Su | 2017 | Zoological Research2017，38，3： | 8 |
| 2 | Epidemiological survey of echinococcosis in Tibet Autonomous Region of China显示文摘Background:The echinococcosis is prevalent in 10 provinces/autonomous region in western and northern China.Epidemiological survey of echinococcosis in China in 2012 showed the average prevalence of four counties in Tibet Autonomous Region(TAR)is 4.23%,much higher than the average prevalence in China(0.24%).It is important to understand the transmission risks and the prevalence of echinococcosis in human and animals in TAR.Methods:A stratified and proportionate sampling method was used to select samples in TAR.The selected residents were examined by B-ultrasonography diagnostic,and the faeces of dogs were tested for the canine coproantigen against Echinococcus spp.using enzyme-linked immunosorbent assay.The internal organs of slaughtered domestic animals were examined by visual examination and palpation.The awareness of the prevention and control of echinococcosis among of residents and students was investigated using questionnaire.All data were inputted using double entry in the Epi Info database,with error correction by double-entry comparison,the statistical analysis of all data was processed using SPSS 21.0,and the map was mapped using ArcGIS 10.1,the data was tested by Chi-square test and Cochran-Armitage trend test.Results:A total of 80384 people,7564 faeces of dogs,and 2103 internal organs of slaughtered domestic animals were examined.The prevalence of echinococcosis in humans in TAR was 1.66%,the positive rate in females(1.92%)was significantly higher than that in males(1.41%),(X2=30.31,P<0.01),the positive rate of echinococcosis was positively associated with age(X2trend=-423.95,P<0.01),and the occupational populations with high positive rates of echinococcosis were herdsmen(3.66%)and monks(3.48%).The average positive rate of Echinococcus coproantigen in TAR was 7.30%.The positive rate of echinococcosis in livestock for the whole region was 11.84%.The average awareness rate of echinococcosis across the region was 33.39%.Conclusions:A high prevalence of echinococcosis is found across the TAR,representing a very serious concern to human health.Efforts should be made to develop an action plan for echinococcosis prevention and control as soon as possible,so as to control the endemic of echinococcosis and reduce the medical burden on the population. | Bin Li Gongsang Quzhen Chui-Zhao Xue Shuai Han Wei-Qi Chen Xin-Liu Yan Zhong-Jie Li MLinda Quick Yong Huang Ning Xiao Ying Wang Li-Ying Wang Gesang Zuoga Bianba Gangzhu Bing-Cheng Ma Gasong Xiao-Gang Wei Niji Can-Jun Zheng Wei-Ping Wu Xiao-Nong Zhou | 2019 | Infectious Diseases of Poverty2019，8，2： | 8 |
| 3 | Blunted nitric oxide regulation in Tibetans under high-altitude hypoxia显示文摘Nitric oxide(NO) is an important molecule for vasomotor tone, and elevated NO signaling was previously hypothesized as a unique and adaptive physiological change in highland Tibetans. However, there has been lack of NO data from Tibetans living at low altitude and lowlander immigrants living at high altitude, which is crucial to test this hypothesis. Here, through cross-altitude(1990–5018 m) and cross-population(Tibetans and Han Chinese) analyses of serum NO metabolites(NOx) of 2086 individuals, we demonstrate that although Tibetans have a higher serum NOx level compared to lowlanders, Han Chinese immigrants living at high altitude show an even higher level than Tibetans. Consequently, our data contradict the previous proposal of increased NO signaling as the unique adaptive strategy in Tibetans.Instead, Tibetans have a relatively lower circulating NOx level at high altitude. This observation is further supported by data from the hypoxic experiments using human umbilical vein endothelial cells and gene knockout mice. No difference is detected between Tibetans and Han Chinese for endothelial nitric oxide synthase(e NOS), the key enzyme for circulating NO synthesis, suggesting that e NOS itself is unlikely to be the cause. We show that other NO synthesis-related genes(e.g. GCH1) carry Tibetan-enriched mutations significantly associated with the level of circulating NOx in Tibetans. Furthermore, gene network analysis revealed that the downregulation and upregulation of NOx is possibly achieved through distinct pathways.Collectively, our findings provide novel insights into the physiological and genetic mechanisms of the evolutionary adaptation of Tibetans to high-altitude hypoxia. | Yaoxi He Xuebin Qi Ouzhuluobu Shiming Liu Jun Li Hui Zhang Baimakangzhuo Caijuan Bai Wangshan Zheng Yongbo Guo Duojizhuoma Baimayangji Dejiquzong Bianba Gonggalanzi Yongyue Pan Qula Kangmin Cirenyangji Wei Guo Yangla Yi Peng Xiaoming Zhang Kun Xiang Zhaohui Yang Liangbang Wang Gengdeng Yanfeng Zhang Tianyi Wu Bing Su Chaoying Cui | 2018 | National Science Review2018，5，4： | 7 |
| 4 | Land use dynamics in Lhasa area, Tibetan Plateau显示文摘陆地使用变化是在社会经济、机构、环境的因素之间的相互影响的结果,并且在为可持续性,食物安全,生物多样性和对全球变化影响的人和生态系统的危险与重要折衷社会经济、环境的系统工作上有重要影响。在在1980年代末执行的西藏自治区域基于第一陆地使用调查的结果,在 1990 的拉萨区域的陆地使用地图用在4月获得的天线相片在拉萨山谷为主要农业区域被编,在1980年代末的5月和1991年10月和 Landsat 形象并且 1991 作为遥远地察觉到的数据采购原料。用这些遥远地察觉到的数据,在 1991, 1992, 1993, 1995, 1999 和 2000 的拉萨区域的陆地使用地位通过等等更新栽培土地,人工的森林,种的草,草地恢复,和居住区域的年度变化被印射。为在 2007 的拉萨区域的陆地使用地图用在 10 月 24 日获得的 ALOS AVNIR-2 合成图象被做,通过更新的 2007 年 12 月 26 日主要陆地使用类型变化。根据在 1990, 1995, 2000 和 2007 的拉萨区域的陆地使用地位,在从 1990 ~ 2007 的拉萨区域的空间、时间的陆地使用动力学进一步在这份报纸用 GIS 空间模型被分析。 | CHU DUO ZHANG Yili BIANBA Ciren LIU Linshan | 2010 | Journal of Geographical Sciences2010，20，6： | 5 |
| 5 | De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation显示文摘Structural variants(SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome(ZF1), with a contig N50 length of 24.57 mega-base pairs(Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps(0.25 Mb in total length) in the reference human genome(GRCh38). Markedly, we detected17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid(Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1(1.32%–1.53%) compared to other East Asian genomes(0.70%–0.98%),reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence-a662-bp intronic insertion in the SCUBE2 gene-is enriched and associated with better lung function(the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies. | Ouzhuluobu Yaoxi He Haiyi Lou Chaoying Cui Lian Deng Yang Gao Wangshan Zheng Yongbo Guo Xiaoji Wang Zhilin Ning Jun Li Bin Li Caijuan Bai Baimakangzhuo Gonggalanzi Dejiquzong Bianba Duojizhuoma Shiming Liu Tianyi Wu Shuhua Xu Xuebin Qi Bing Su | 2020 | National Science Review2020，7，2： | 4 |
| 6 | EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production显示文摘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. | Wang-Shan Zheng Yao-Xi He Chao-Ying Cui Ouzhuluobu Dejiquzong Yi Peng Cai-Juan Bai Duojizhuoma Gonggalanzi Bianba Baimakangzhuo Yong-Yue Pan Qula Kangmin Cirenyangji Baimayangji Wei GUO Yangla Hui Zhang Xiao-Ming Zhang Yong-Bo Guo Shu-Hua Xu Hua Chen Sheng-Guo Zhao Yuan Cai Shi-Ming Liu Tian-Yi Wu Xue-Bin Qi Bing Su | 2017 | Zoological Research2017，38，3： | 4 |
| 7 | Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans显示文摘AIM:To investigate the relationship between CD14-260and-651 polymorphisms and the risk of developing gastric cancer.METHODS:DNA was extracted from peripheral blood samples obtained from 225 Tibetans with gastric cancer and 237 healthy Tibetans,and analyzed using the polymerase chain reaction/ligase detection(PCR/LDR)method to determine the genotypes at-260 and-651loci of the CD14 promoter.The allele frequencies,genotype frequencies,and haplotypes were analyzed for their association with gastric cancer risk using online SHEsis software.The luciferase reporter assay and point mutation analysis were used to construct in vitro plasmids expressing a C/T homozygote at the-260 lo-cus of the CD14 promoter.RESULTS:The frequencies of CC,CT and TT genotypes in the CD14-260 C/T locus in gastric cancer patients were 19.1%,38.7%and 42.2%,respectively,whereas they were 33.3%,32.5%and 34.2%,respectively,in healthy control subjects.CT genotype carriers were more frequently found among gastric cancer patients than healthy controls(OR=2.076;95%CI:1.282-3.360).Also,TT genotype carriers were more frequently found among gastric cancer patients(OR=2.155;95%CI:1.340-3.466).Compared to the C allele of CD14/-260,the T allele was associated with an increased risk for gastric cancer(OR=1.574;95%CI:1.121-2.045).Furthermore,the frequencies of CC,CT and TT in the CD14-651 C/T locus in gastric cancer patients were 64.4%,29.3%and 6.2%,respectively,while they were 56.5%,35.0%and 8.4%,respectively,in the healthy control subjects(P>0.05).Data obtained using the luciferase reporter assay showed that the p260T homozygote was associated with greater CD14 promoter activity(P<0.01).CONCLUSION:CD14/-260 polymorphism is associated with gastric cancer risk in Highland Tibetans and affects CD14 promoter activity,thereby regulating CD14expression. | Kang Li Zeng Dan Xue-Jun Hu Luo-Bu Gesang Yong-Ge Ze Zha-Xi Bianba Cuo-Mu Ciren Yu-Qiang Nie | 2014 | World Journal of Gastroenterology2014，20，10： | 3 |
| 8 | Hematological parameters in high altitude residents:Tibetan natives versus Han migrants显示文摘Objective Aim of our study was to compare hematological parameters in Tibetan natives with those in Han migrants living on the Tibet plateau in order to determine the potential effects of age,gender,and ethnicity on hematological response to hypoxia.Methods Blood hemoglobin(Hb,g/dl),hematocrit(Hct,%),red blood cells(RBC,10~6/mm^3) were measured in 3 588 healthy Tibetan natives and 3 371 Han migrants ranging in age from 5 to 72 years,living at a mean altitudes of 2 664 m,3 813 m,4 525 m and 5 226 m.Results Hemoglobin(Hb) concentration analysis was made by multiple regression equations relating hemoglobin to altitude and age.For 2 093 Han males,Hb =9.612+ 0.001440xaltitude+ 0.06148 xage.For1 948 Tibetan males,Hb =12.202+ 0.000462xaltitude+ 0.02893 xage.For 1 278 Han females,Hb = 10.858+0.000939xaltitude+ 0.02632 xage.For 1 640 Tibetan females,Hb =11.402+ 0.000626xaltitude+ 0.00412 xage.Each of the four equations was statistically significant(P<0.001),and had variance(r2) of 0.86 or more,indicating that altitude and age accounted for at least 85%of the variation in hemoglobin levels.The coefficients for altitude and for age were higher(P<0.05) in Han males than in Tibetan males and higher(P<0.05)in Han females than in Tibetan females.The Tibetan postmenopausal females had higher Hb values than premenopausal females only presented at altitude above 4 000 m while this phenomenon was beginning at altitude of 2 664 m among Han females.Conclusion We conclude that gender and increasing age in Tibetans are associated with lower hemoglobin values than those in Han at high altitude,and we speculate that genetic factors seems to be important. | Tian-yi WU Feng-yun LIU Ling HU Chun-yin WEI Zhi-gang WANG Ouzhou-LOUBU Chao-ying CU Bianba Xue-bin QI Bing SU | 2014 | 中国应用生理学杂志2014，30，6： | 2 |
| 9 | Exercise capacity and selected physiological factors by ancestry and residential altitude: cross-sectional studies of 9-10-year-old children in Tibet显示文摘 | Bianba Berntsen S Andersen LB | 2014 | High Alt Med Biol2014，15，2： | 1 |
| 10 | Altitude adaptation in Tibetans caused by introgression of Denisovan- like DNA显示文摘 | HUERTA-SANCHEZ E JIN X BIANBA Z | 2014 | Nature2014，512，7513： | 1 |
| 11 | Estimation of peak oxygen uptake from maximal power output among 9-10 year-old children in Lhasa, Tibet显示文摘 | Bianba B Berntsen S Andersen LB | 2010 | J Sports Med Plays Fitness2010，50，3： | 1 |
| 12 | Historic Development Of the Tibetan Population显示文摘The Tibet Autonomous Region in China's Far West, with an aver-age elevation above 3,000 meters, suffers from oxygen deficiency and inferior natural conditions,which led to low life expectancy in the past. The population reported by the local former government of Tibet was 1 million according to the first census of | GARMA DORJE HUANG YAN BIANBA CERING | 2004 | China's Tibet2004，15，4： | 0 |
| 13 | Clinical and etiological characteristics of community-acquired pneumonia at high altitudes in Tibet, China显示文摘To the Editor:Community-acquired pneumonia(CAP)is one of the most common infectious diseases,causing high morbidity and mortality.High altitudes are characterized by a hypoxic environment with low barometric pressure,increased ultraviolet radiation,and low humidity.Hypoxia can disturb normal homeostasis of the immune system,especially impairing the function of the T lymphocytes,leading to an increased susceptibility to bacterial infection.The respiratory symptoms of CAP at high altitudes are similar to that of high-altitude pulmonary edema. | Qucuo Meilang Ran Li Xue-Mei Wu Ying Shang Pu Ning Jing Bao Qiongda Bianba Zhuoga Pubu Li-Ping Huang Zhan-Cheng Gao | 2021 | Chinese Medical Journal2021，，6： | 0 |
| 14 | Prevalence and risk factors for minimal hepatic encephalopathy in cirrhotic patients with different etiologies显示文摘Aims:Minimal hepatic encephalopathy(MHE)significantly affects the prognosis of patients with cirrhosis.This study was performed to determine whether there is a difference in the prevalence of MHE among patients with cirrhosis of different etiologies and whether the etiology directly influences the occurrence of MHE.Methods:This multicenter,cross-sectional study enrolled 1879 patients with confirmed cirrhosis at 40 hospitals from October 25,2021,to January 10,2023(Trial registration:http://gffzzd3f38a9638994581s099cpn56q9c669qk.ffgz.tsg.suse.edu.cn/[NCT05140837]).The patients'demographics,etiologies of cirrhosis,and laboratory test results were collected.The psychometric hepatic encephalopathy score(PHES)was determined in all patients to screen for MHE.Multivariate logistic analyses were performed to identify the risk factors for MHE.Results:In total,736 patients with cirrhosis were analyzed.The prevalence of MHE was 42.0%(n=309).The primary etiology among all patients was hepatitis B virus(HBV)-related cirrhosis(71.9%[529/736]).The prevalence of MHE was significantly higher in patients with alcoholic cirrhosis(57.1%[40/70])than in those with HBV-related cirrhosis(40.6%[215/529],p=0.009)or hepatitis C virus(HCV)-related cirrhosis(38.2%[26/68],p=0.026).Age(odds ratio[OR],1.042;95%confidence interval[CI],1.024-1.059;p<0.001),duration of education(OR,0.935;95%CI,0.899-0.971;p=0.001),etiology(OR,1.740;95%CI,1.028-2.945;p=0.039),and high MELD-Na scores(OR,1.038;95%CI,1.009-1.067;p=0.009)were independent risk factors for MHE.When patients with cirrhosis of different etiologies were analyzed separately,the results showed that age(OR,1.035;95%CI,1.014-1.057;p=0.001)and duration of education(OR,0.924;95%CI,0.883-0.966;p=0.001)were risk factors for MHE among patients with HBV-related cirrhosis,whereas age(OR,1.138;95%CI,1.033-1.254;p=0.009)and creatinine concentration(OR,16.487;95%CI,1.113-244.160;p=0.042)were risk factors for MHE in patients with HCV-related cirrhosis.No risk factors for MHE were found in patients with autoimmune cirrhosis.For patients with alcoholic cirrhosis,the platelet count(OR,1.014;95%CI,1.000-1.027;p=0.045)was a risk factor for MHE.The PHES subtest results were inconsistent among patients who had MHE with cirrhosis of different etiologies.Patients with HBV-related cirrhosis performed better on Number Connection Test B and the serial dotting test than those with alcoholic cirrhosis(p=0.007 and p<0.001),better on Number Connection Test B than those with HCV-related cirrhosis(p=0.020),and better on the line tracing test than those with autoimmune cirrhosis(p=0.037).Conclusion:The etiology of cirrhosis affected the prevalence of MHE and risk factors for MHE.The domains of major cognitive impairment varied among patients with cirrhosis of different etiologies.Further studies are required to verify these findings. | Xiaoyan Li Shanghao Liu Huiling Xiang Qingge Zhang Ying Guo Hongmei Zu Jing Wang Jiaojian Lv Xiaoning Zhang Fanping Meng Jiahuan Li Jie Li Yangzhen Bianba Jia Shang Guo Zhang Fei Liu Zhaowei Tong Chuang Lei Wei Ye Qiaohua Yang Ningning Wang Ying Song Wei Fu Ziyue Li Yanjing Gao Yongping Zhang Jiafang Chen Caiyun Wu Qi Zheng Fang Wang Jiali Yu Lianjie Lin Chuanlong Yang Xiaoting Yang Xiaomin Ye Xiangmei Wang Xuelan Zhao Xiaolong Qi Fusheng Wang Junliang Fu | 2023 | Portal Hypertension & Cirrhosis2023，2，4： | 0 |
| 15 | Children's exercise capacity at high altitude in Tibet显示文摘Maximal oxygen uptake(exercise capacity) is a vital parameter in the evaluation of adaptation to high altitude,providing an index of the integrated function of the oxygen transport system.Previous studies of maximal oxygen uptake in population at high altitude have mainly focused on adults and adolescents,though data on children are uncommon.Maximal oxygen uptake can be measured directly,using an oxygen analyser,or indirectly through the development of equations for estimation from the maximal power output(W_(max)).Such estimations and studies of the physiological aspects of children's capacity to work and live at different altitudes in Tibet ancestry were not reported previously,although differences similar to those seen in adults may be expected to occur.The present paper summarized the findings of studies on exercise capacity among children living at high altitude in Tibet. | Bianba Lars Bo Andersen Hein Stigum Ouzhuluobu Espen Bjertness | 2014 | 中国应用生理学杂志2014，30，6： | 0 |
| 16 | DLG7/DLGAP5 as a potential therapeutic target in gastric cancer显示文摘To the Editor:Gastric cancer is a highly invasive disease.An estimated 1.09 million cases were diagnosed and 770,000 gastric cancer-related deaths occurred only in 2020.[1]Advanced gastric cancer can no longer be subjected to surgery and can only be treated with sequential lines of chemotherapy.However,the survival period is usually short.[2]Therefore,it is of utmost importance to identify new and more effective treatments and therapeutic targets to combat gastric cancer.Disc large homolog 7(DLG7)is the microtubule-associated protein encoded by the DLG associated protein 5(DLGAP5)gene,which affects chromosome rearrangement and gene stability[3];thus,its overexpression may cause canceration.Some studies revealed that DLGAP5 is highly expressed in gastric cancer tissues,suggesting that it may also have a role in this disease.However,the role and mechanism of DLGAP5 in gastric cancer are still unclear.[4]Therefore,this study aimed at exploring the role of DLGAP5 in the growth and invasion of gastric cancer as well as the potential use as a therapeutic target to combat this disease. | Kang Li Xiangsheng Fu Ping Wu Bianba Zhaxi Hanhuan Luo Qijie Li | 2022 | Chinese Medical Journal2022，，13： | 0 |
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