The transcriptomic and epigenetic alterations in type 2 diabetes mellitus patients of Chinese Tibetan and Han populations.

Background: Due to the distinctive living environment, lifestyle, and diet, the Tibetan community in China has the lowest prevalence of T2DM and prediabetes among numerous ethnic groups, while Han community shows the highest statistic. In this study, we aim to conclude the clinical manifestations of both Tibetan and Han T2DM patients and their association with transcriptomic and epigenetic alterations. Methods: A cross-sectional study including 120 T2DM patients from Han and Tibetan ethnic groups were conducted between 2019 to 2021 at the Hospital of Chengdu University of Traditional Chinese Medicine. The various clinical features and laboratory tests were recorded and analyzed between the two groups. The genome-wide methylation pattern and RNA expression were determined by Reduced Representation Bisulfite Sequencing (RBBS) and Poly (A) RNA sequencing (RNA-seq) from leucocytes of peripheral blood samples in 6 Han and 6 Tibetan patients. GO analysis and KEGG analysis were conducted in differentially expressed genes and those with differentially methylated regions. Results: Compared to Han, Tibetan T2DM individuals intake more coarse grains, meat and yak butter, but less refined grains, vegetables and fruit. They also showed increased BMI, Hb, HbA1c, LDL, ALT, GGT and eGFR, and decreased level of BUN. Among the 12 patients in the exploratory cohort, we identified 5178 hypomethylated and 4787 hypermethylated regions involving 1613 genes in the Tibetan group. RNA-seq showed a total of 947 differentially expressed genes (DEGs) between the two groups, with 523 up-regulated and 424 down-regulated in Tibetan patients. By integrating DNA methylation and RNA expression data, we identified 112 DEGs with differentially methylated regions (overlapping genes) and 14 DEGs with promoter-related DMRs. The functional enrichment analysis demonstrated that the overlapping genes were primarily involved in metabolic pathways, PI3K-Akt signaling pathway, MAPK signaling pathway, pathways in cancer and Rap1 signaling pathway. Conclusion: Our study demonstrates the clinical characteristics of T2DM differ subtly between various ethnic groups that may be related to epigenetic modifications, thus providing evidence and ideas for additional research on the genetic pattern of T2DM.

Dietary and drinking water intake of essential trace elements in a typical Kashin-Beck disease endemic area of Tibet, China.

BACKGROUND: Essential trace elements (ETEs), such as copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), are very important elements for human health. METHODS: In this study, 89 drinking water samples and 85 highland barleys were collected from 48 villages in 11 townships, and the average daily dose (ADD) of ETEs were calculated, in addition, health effects of ETEs to rural residents in Luolong County, a typical Kashin-Beck disease (KBD) endemic area in Tibet, were assessed. RESULTS: The mean concentrations of Cu, Fe, Mn, Mo, Se, Zn in drinking water were 0.278 ± 0.264 µg·kg-1, 0.766 ± 0.312 µg·kg-1, 0.411 ± 0.526 µg·kg-1, 0.119 ± 0.223 µg·kg-1, 0.155 ± 0.180 µg·kg-1, and 0.804 ± 1.112 µg·kg-1, respectively; and mean concentrations of Cu, Fe, Mn, Mo, Se and Zn in highland barley were 3.550 ± 0.680 mg·kg-1, 81.17 ± 38.14 mg·kg-1, 14.03 ± 1.42 mg·kg-1, 0.350 ± 0.200 mg·kg-1, 0.0028 ± 0.0056 mg·kg-1, and 23.58 ± 3.10 mg·kg-1, respectively. The ADD of Cu in the study area was appropriate; the ADD of Fe and Mn in each township were higher than the maximum oral reference dose recommended by the National Health Commission of China, indicating that Fe and Mn had non-carcinogenic health risks; the ADD of Mo and Zn in 36.36% and 54.55% of the townships exceeded the maximum oral reference dose; and 72.73% of the townships had insufficient ADD of Se. The ADD of Mo, Cu and Se in different townships was significantly correlated with the prevalence of KBD. CONCLUSIONS: Therefore, in order to prevent and control the prevalence of KBD and ensure the health of local residents, it is necessary to reduce the intake of high concentrations of Fe, Mn and Zn in diet, as well as increase the intake of Mo, Cu, especially Se.

Hydrochemical characteristics of surface waters and their relationships to the Kashin-Beck Disease in Longzi County, Tibet.

Although previous studies have been reported between the Kashin-Beck Disease (KBD) epidemic and the hydrochemical characteristics of surface waters, the etiology of the disease remains unclear. In the present study, we comprehensively investigated the relationship between the KBD and the hydrochemical characteristics of surface waters in Longzi County. Results show that, the pH (mean = 7.27 ± 0.30), total hardness (TH, mean = 57.08 ± 45.74 mg L-1), total dissolved solids (TDS, mean = 67.56 ± 44.00 mg L-1) and oxidation-reduction potential (ORP, mean = 84.11 ± 23.55 mV) of surface waters in KBD endemic areas are lower than those in the non-KBD endemic areas (means of pH = 7.49 ± 0.30; TH = 262.06 ± 123.29 mg L-1; TDS = 253.25 ± 100.39 mg L-1; ORP = 215.90 ± 55.99 mV). These results suggest that long-term consumption of low TDS, essential trace elements (e.g., nickel, cobalt, iron, selenium, zinc, molybdenum, and iodine) deficient, and potential toxic elements (e.g., arsenic) enriched waters by humans likely causes the KBD. Environmental factors such as the geology and geomorphology may produce biogeochemical imbalance, geomorphic, vegetation types and local climatic conditions may have significant impact on food fungi toxin poisoning and water organic compound poisoning, and these also impact the KBD occurrence.

Association between Bone Morphogenetic Protein 2 Gene Polymorphisms and Skeletal Fluorosis of The Brick-tea Type Fluorosis in Tibetans and Kazakhs, China.

To investigate the potential association between BMP2 single nucleotide polymorphisms (SNPs) and brick-tea-type skeletal fluorosis risk in cross-sectional case-control study conducted in Sinkiang and Qinghai, China, a total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled. Using the standard WS/192-2008 (China), 221 skeletal fluorosis cases were diagnosed, including 123 Tibetans and 98 Kazakhs. Logistic regressions 2 analysis did not find the association between SNPs (Rs235764, Rs235739 and Rs996544) and skeletal fluorosis. Genetic models, linkage disequilibrium (LD) and haplotype analysis were not found to be associated with risk of skeletal fluorosis after adjustment by age and sex (P>0.05).Our data suggested that Rs 235764, Rs 235739 and Rs 996544 were not linked susceptibility for skeletal fluorosis in our cross-sectional case-control study.

Assessing the Health Loss from Kashin-Beck Disease and Its Relationship with Environmental Selenium in Qamdo District of Tibet, China.

Kashin-Beck Disease (KBD) is one of major endemic diseases in China. In this study, we estimated the health loss from KBD in Qamdo district of Tibet using the years lived with disability (YLD) metric and investigated the influence of environmental selenium (Se) on it by multiple regression model. The results showed that YLD rates produced a different ranking of health loss of KBD from that produced by prevalence rates between Basu and Luolong County, with higher health loss from KBD (43.61 YLD/1000) but lower prevalence (17.86%) in Basu County. YLD rates in two counites were both highest for the 45-64 years age group. Compared with the prevalence rate, the YLD rate had a closer relation to environmental Se and was significantly negatively correlated with Se in both soil and highland barley. The multiple linear regression further revealed that Se contents in cultivated soil and highland barley were main influencing factors for the health loss of KBD, which could explain 90.5% of the variation in YLD rates. The information obtained highlights the significance of the YLD metric in exploring the environmental etiology of KBD and provides important information on which to base decisions on future prevention and control of endemic diseases.

Brick tea consumption is a risk factor for dental caries and dental fluorosis among 12-year-old Tibetan children in Ganzi.

Brick tea contains high concentration of fluoride. The aim of the present work was to explore whether and how the brick tea is a risk factor for dental caries and dental fluorosis among Tibetan children in Ganzi. A cross-sectional study was conducted with 368 12-year-old Tibetan children in Ganzi. Dental caries was measured by DMFT index, and dental fluorosis severity was measured by Dean's Index. Community Fluorosis Index was used to estimate public health significance of dental fluorosis. Oral health-related behaviors and awareness, dietary habits and socioeconomic status were determined by a questionnaire. Bivariate and multivariate analyses were used to determine risk factors associated with dental caries and dental fluorosis. Dental caries prevalence was 37.50%, mean DMFT was 0.84 ± 1.53, while dental fluorosis prevalence was 62.23%. Community Fluorosis Index was 1.35, indicating a medium prevalent strength of dental fluorosis. Dental fluorosis was associated with mother's regular consumption of brick tea and residence altitude, and dental caries was associated with mother's regular consumption of brick tea. Mother's regular consumption of brick tea was a risk factor for both dental fluorosis and dental caries among children. Reducing mother's brick tea consumption during pregnancy and lactation may improve oral health status of their children.

Trace Element Levels in Scalp Hair of School Children in Shigatse, Tibet, an Endemic Area for Kaschin-Beck Disease (KBD).

Kaschin-Beck disease (KBD) is an endemic osteoarthritis, and the etiology is closely related with levels of trace elements in the human body. Currently, it is clear that the selenium (Se) status of children in KBD areas is lower than that in non-KBD areas in the Tibetan Plateau, whereas role of other elements are yet unknown. This study aimed to assess some essential trace elements (Se, Mo, Mn, Zn, Fe, Cu, Co, and Sr) in children using scalp hair as a biomarker, and 157 samples from school children aged 8-14 years old were collected from both KBD and non-KBD areas in Shigatse, Tibet. Se and Mo were measured by inductive coupled plasma mass spectrometry, and the other elements were determined by inductive coupled plasma optical emission spectrometry. Compared with the non-KBD areas, Se, Mo, Mn, Fe, Zn, Co, and Sr levels of children in KBD areas were found to be significantly different (P < 0.05); while in linear discriminant analysis, only Se and Zn were found to contribute to the KBD prevalence in the study area. The hair Se level of children in KBD areas ranged from 0.115 to 0.299 mg/kg, while in non-KBD areas it ranged from 0.135 to 0.519 mg/kg. The Zn content of children's hair was between 83 and 207 mg/kg in KBD areas, while it was 37 and 219 mg/kg in non-KBD areas. Lower Se and higher Zn levels in children in KBD areas was found when compared with non-KBD groups. In addition, Mo levels were found to be different between KBD areas and non-KBD areas on the opposite side of the Yarlung Zangbo River, but no close relationship was shown because there was no difference compared with the non-KBD area on the same side of the river. Our observations suggest that Se deficiency is still an important factor for the occurrence and prevalence of KBD, while the relationship between Zn and KBD needs to be further explored in the Tibetan Plateau.

Effect of calcium and vitamin D on growth, rickets and Kashin-Beck disease in 0- to 5-year-old children in a rural area of central Tibet.

OBJECTIVE: To evaluate the effect of calcium (15 mmol/day) and vitamin D (625 µg/month), as single supplement or in combination, vs. no supplement on growth, clinical signs of rickets and Kashin-Beck disease (KBD) and dental health. METHODS: Prospective controlled trial involving children aged 0-5 years living in four groups of villages in a KBD-endemic rural area of central Tibet who received either calcium and/or vitamin D or no supplement. The cohort was followed over 3 years. Primary outcome was the impact of the different supplementation regimes on KBD, rickets and growth; secondary outcomes were impact on urinary levels of calcium and phosphorus, biomarkers of bone and cartilage turnover, and dental health. RESULTS: No difference was observed between the four groups with regard to anthropometric data, rickets, KBD, urinary levels of CrossLaps(®) and CartiLaps(®) . Weight for height or age, mid-upper arm circumference and skinfold thickness decreased in the four groups. Height for age increased and the prevalence of KBD fell in the four groups. Dental health was better in the group receiving calcium and vitamin D. Urinary calcium levels increased after 3 years of follow-up in all groups; the group receiving vitamin D had a higher increase (P-value: 0.044). The same global increase was observed for urinary phosphorus levels; the group receiving calcium had a higher increase (P-value: 0.01). CONCLUSIONS: Calcium and vitamin D failed to improve growth and bone metabolism of children living in a KBD-endemic rural area. Calcium and vitamin D supplementation improved dental health.

Prevalence of Brick Tea-Type Fluorosis in the Tibet Autonomous Region.

BACKGROUND: The prevalence of brick tea-type fluorosis is high in Tibet because of the habit of drinking brick tea in this region. Brick tea-type fluorosis has become an urgent public health problem in China. METHODS: A cross-sectional survey was conducted to investigate prevalence of brick tea-type fluorosis in all districts of Tibet using a stratified cluster sampling method. Dental fluorosis in children aged 8-12 years and clinical skeletal fluorosis in adults were diagnosed according to the national criteria. A total of 423 children and 1320 adults participated in the study. Samples of drinking water, brick tea, brick tea infusion (or buttered tea), and urine were collected and measured for fluoride concentrations by the fluoride ion selective electrode method. RESULTS: The fluoride level in all but one of the brick tea samples was above the national standard. The average daily fluoride intake from drinking brick tea in all seven districts in Tibet was much higher than the national standard. The prevalence of dental fluorosis was 33.57%, and the prevalence of clinical skeletal fluorosis was 46.06%. The average daily fluoride intake from drinking brick tea (r = 0.292, P < 0.05), urine fluoride concentrations in children (r = 0.134, P < 0.05), urine fluoride concentrations in adults (r = 0.162, P < 0.05), and altitude (r = 0.276, P < 0.05) were positively correlated with the prevalence of brick tea-type fluorosis. Herdsmen had the highest fluoride exposure and the most severe skeletal fluorosis. CONCLUSIONS: Brick tea-type fluorosis in Tibet is more serious than in other parts of China. The altitude and occupational factors are important risk factors for brick tea-type fluorosis.

PREVALENCE OF SULFONAMIDE AND FLORFENICOL RESISTANCE GENES IN ESCHERICHIA COLI ISOLATED FROM YAKS (BOS GRUNNIENS) AND HERDSMEN IN THE TIBETAN PASTURE.

To determine the antimicrobial susceptibility profiles and prevalence of resistance genes in Escherichia coli isolated from yaks (Bos grunniens) and herdsmen in nine plateau pastures in Tibet, we isolated 184 nonidentical strains of E. coli from yaks and herdsmen. Antimicrobial susceptibility testing of 15 antimicrobials was conducted and the prevalence of sulfonamide resistance genes (sul1, sul2, and sul3) and florfenicol resistance genes (floR, cfr, cmlA, fexA, pexA, and estDL136) was determined. Escherichia coli isolated from yaks had a high resistance rate to sulfamethoxazole (44%), sulphafurazole (40.4%), and florfenicol (11.4%). Escherichia coli isolated from herdsmen had a high resistance rate to sulfamethoxazole (57%) and sulphafurazole (51%). In addition, sul genes were present in 93% of sulfonamide-resistant isolates (84/90), and 17 floR genes and four cmlA genes were found in 19 florfenicol-resistant isolates. Even though florfenicol is prohibited from use in humans, three floR genes were detected in strains isolated from herdsmen. The three floR-positive isolates from herdsmen had pulsed-field gel electrophoresis patterns similar to isolates from yaks. In addition to documenting the sul and floR genes in E. coli isolated from yaks and herdsmen in the Tibetan pasture, we demonstrated the potential risk that antimicrobial-resistant E. coli could spread among herdsmen and yaks.

Hair Selenium Levels of School Children in Kashin-Beck Disease Endemic Areas in Tibet, China.

Previous studies have shown that the selenium (Se) deficiency is an important factor for the etiology of Kashin-Beck disease (KBD). Although KBD is presently controlled in most regions of China, it is still active in the Tibetan Plateau. The present study aimed to assess the nutritional status of selenium in school children by using the Se level in hair as a biomarker in KBD endemic areas of Lhasa in Tibet, China. Hair samples of 155 school children aged 6-15 years were collected in both KBD areas and non-KBD areas of Lhasa in 2013. The Se level in the hair samples was determined by inductive coupled plasma mass spectrometry (ICP-MS). The average concentration of Se in children's hair was 0.232 µg/g in KBD areas of Lhasa, which was significantly higher than the data reported decades ago. A significant difference in hair Se was observed between the boys (0.255 µg/g) and the girls (0.222 µg/g) in the studied KBD areas (P < 0.01, Mann-Whitney U test), but hair Se did not vary by age or region. School children in KBD endemic areas in Lhasa likely have improved Se status as a result of high Se content staple food substitution with the enforcement of Free Education Policy and Nutrition Improvement Plan in Tibet. Nevertheless, there were still 20.3 % of students with low Se status (hair Se <0.20 µg/g), which showed that Se status of school children was also partly affected by low Se environment in KBD endemic areas of Lhasa.

Reducing high maternal mortality rates in western China: a novel approach.

Among the Millennium Development Goals, maternal mortality reduction has proven especially difficult to achieve. Unlike many countries, China is on track to meeting these goals on a national level, through a programme of institutionalizing deliveries. Nonetheless, in rural, disadvantaged, and ethnically diverse areas of western China, maternal mortality rates remain high. To reduce maternal mortality in western China, we developed and implemented a three-level approach as part of a collaboration between a regional university, a non-profit organization, and local health authorities. Through formative research, we identified seven barriers to hospital delivery in a rural Tibetan county of Qinghai Province: (1) difficulty in travel to hospitals; (2) hospitals lack accommodation for accompanying families; (3) the cost of hospital delivery; (4) language and cultural barriers; (5) little confidence in western medicine; (6) discrepancy in views of childbirth; and (7) few trained community birth attendants. We implemented a three-level intervention: (a) an innovative Tibetan birth centre, (b) a community midwife programme, and (c) peer education of women. The programme appears to be reaching a broad cross-section of rural women. Multilevel, locally-tailored approaches may be essential to reduce maternal mortality in rural areas of western China and other countries with substantial regional, socioeconomic, and ethnic diversity.

Association study of polymorphisms in selenoprotein genes and Kashin-Beck disease and serum selenium/iodine concentration in a Tibetan population.

BACKGROUND: Kashin-Beck disease is a kind of degenerative osteoarthropathy. Genetic factors may play an important role in the pathogenesis of KBD. OBJECTIVE: To investigate the association of the selenoprotein genes GPX1 (rs1050450, rs1800668, and rs3811699), TrxR2 (rs5748469), and DIO2 (rs225014) with Kashin-Beck disease (KBD) in a Tibetan population and to investigate the association of these SNPs with the serum iodine/selenium concentration in the Tibetan population. DESIGN: Five SNPs including rs1050450, rs1800668, and rs3811699 in the GPX1 gene, rs5748469 in the TrxR2 gene, and rs225014 in the DIO2 gene were analyzed in Tibetan KBD patients and controls using the SNaPshot method. P trend values of the SNPs were calculated using an additive model. RESULTS: None of the five SNPs in the three genes showed a significant association with KBD. Haplotypes TCC, TTC and TTT of rs1050450, rs1800668 and rs3811699 in GPX1 showed a significant association with KBD and controls with P value of 0.0421, 5.0E-4 and 0.0066, respectively. The GPX1 gene (rs1050450) showed a potential significant association with the iodine concentration in the Tibetan study population (P = 0.02726). However, no such association was detected with the selenium concentration (P = 0.2849). CONCLUSIONS: In this study, we showed that single SNPs in the genes GPX1 (rs1050450, rs1800668 and rs3811699), TrxR2 (rs5748469), and DIO2 (rs225014) may not be significantly associated with KBD in a Tibetan population. However, haplotype analysis of SNPs rs1050450, rs1800668 and rs3811699 in GPX1 gene showed a significant association with KBD. The results suggested that GPX1 gene play a protective role in the susceptivity of KBD in Tibetans. Furthermore, the GPX1 gene (rs1050450) may be significantly associated with the serum iodine concentration in Tibetans.

Selenium: a protective factor for Kaschin-Beck disease in Qing-Tibet Plateau.

There is a close relationship between selenium deficiency and Kaschin-Beck disease (KBD). Although the etiology of KBD is not known and selenium deficiency is not its actual cause, it is an important environmental risk factor. In particular, in the Qing-Tibet Plateau, a selenium-deficient region, the prevalence of KBD is serious and still increasing and continues to damage public health. By providing selenium to the population in appropriate amounts, and especially to children, KBD can be effectively controlled and prevented.

Growth, nutritional status, and signs of rickets in 0-5-year-old children in a Kashin-Beck disease endemic area of Central Tibet.

UNLABELLED: In order to describe the growth of 0-5-year-old Tibetan children living in a Kashin-Beck disease (KBD) endemic rural area and to examine the relationship between anthropometric indicators and clinical signs of rickets, we analyzed the baseline data of a cohort of 668 children enrolled in a prospective program of calcium and vitamin D supplementation. Tibetan children suffer from growth retardation. Z score of weight-for-age, height-for-age, weight-for-height was below -2 in 32.5%, 27.7%, and 12.1% of the children, respectively. Clinical signs of severe rickets are highly prevalent. Underweight, stunting, and clinical rickets increases with age. Prevalence of malnutrition was higher in the presence of signs of rickets. The proportion of children with a head circumference Z score < -2 was lowest when signs of rickets were observed. CONCLUSION: Stunting and underweight are frequent and probably associated with rickets.

Environmental selenium in the Kaschin-Beck disease area, Tibetan Plateau, China.

Now, there is a decreasing trend for the prevalence rate of Kaschin-Beck disease (KBD) in most parts of China, but the disease is still active and severe in the Tibetan Plateau for some reason. To further explore the role of selenium in the occurrence of KBD, We collected samples including drinking water, cultivated topsoil, Highland Barley grains, and tsamba in Rangtang County and Aba County, Sichuan Province and determined concentrations of selenium by Hydride Generation Atomic Fluorescence Spectrometry. Levels of selenium in the environment were analyzed in detail. Selenium in the soil-plant-food system and their relationship with prevalence rate of KBD were also discussed. The results indicate: (a) the levels of environmental selenium are very low and the study area belongs to a selenium-deficient ecological landscape; (b) the KBD becomes much more severe with decreasing environmental selenium under the selenium-deficient condition. Namely, the lower the environmental selenium is, the more severe the disease is; (c) soil selenium deficiency plays a critical role for the prevalence of local KBD, and more factors inducing selenium deficiency should be more concerned in the future.

Pregnancy and Village Outreach Tibet: a descriptive report of a community- and home-based maternal-newborn outreach program in rural Tibet.

OBJECTIVE: The Pregnancy and Village Outreach Tibet (PAVOT) program, a model for community- and home-based maternal-newborn outreach in rural Tibet, is presented. METHODS: This article describes PAVOT, including the history, structure, content, and activities of the program, as well as selected program outcome measures and demographic characteristics, health behaviors, and pregnancy outcomes of women who recently participated in the program. RESULTS: The PAVOT program was developed to provide health-related services to pregnant rural Tibetan women at risk of having an unattended home birth. The program involves training local healthcare workers and laypersons to outreach pregnant women and family members. Outreach includes basic maternal-newborn health education and simple obstetric and neonatal life-saving skills training. In addition, the program distributes safe and clean birth kits, newborn hats, blankets, and maternal micronutrient supplements (eg, prenatal vitamins and minerals). More than 980 pregnant women received outreach during the study period. More than 92% of outreach recipients reported receiving safe pregnancy and birth education, clean birthing and uterine massage skills instruction, and clean umbilical cord care training. Nearly 80% reported basic newborn resuscitation skills training. Finally, nearly 100% of outreach recipients received maternal micronutrient supplements and safe and clean birth kits. CONCLUSION: The PAVOT program is a model program that has been proven to successfully provide outreach to rural-living Tibetans by delivering maternal-newborn health education, skills training, and resources to the home.

Having a "safe delivery": conflicting views from Tibet.

In the Tibetan Autonomous Region (TAR) of the People's Republic of China (PRC) maternal mortality ratios remain among the highest in the world. Although traditional Tibetan medical theory, practice, and pharmacology include information on maternal and child health care, Tibet is one of the few societies in the world that does not have traditional birth attendants or midwives. Using ethnographic methods, we gathered data from individual interviews with rural Tibetan women (N=38) about their beliefs and behaviors surrounding pregnancy and childbirth. Additional data were gathered through interviews with prefecture, county, and township health care providers. These data were used to develop a culturally appropriate village birth attendant training program in rural Tibet. We describe Tibetan women's perspectives of "having a safe delivery" in relation to concepts about "safe delivery" according to evidence-based medicine in the West. Our work also provides an example of the benefits and challenges that arise when ethnographic research methods are used to design and implement health care interventions.

Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy.

BACKGROUND: Kashin-Beck disease is an osteoarthropathy endemic in selenium- and iodine-deficient areas around Lhasa, Tibet. OBJECTIVE: We assessed the efficacy of selenium supplementation on disease progression. DESIGN: A double-blind, randomized controlled trial of selenium supplementation was carried out in 324 children aged 5-15 y who had Kashin-Beck disease. Two hundred eighty children received iodized oil before being randomly assigned to receive selenium or placebo, and a control group of 44 subjects was not supplemented at all. Clinical and radiologic signs, selenium status, urinary iodine, and thyroid function were evaluated at baseline and at 12 mo. RESULTS: The frequencies of joint pain, decreased joint mobility, and radiologic abnormalities were not significantly different between the 3 groups at 12 mo. Height-for-age z scores increased significantly in the subjects who received placebo and iodine or selenium and iodine. In contrast, unsupplemented control subjects did not recover from growth retardation. Serum selenium concentrations at 12 mo were within the reference range and were significantly greater in the selenium-iodine group than in the placebo-iodine group. Serum thyroid hormone concentrations were within the reference ranges after the administration of iodine, and these values were not significantly affected by selenium supplementation. CONCLUSIONS: The results of this study do not rule out the possibility that selenium may help to prevent the occurrence of Kashin-Beck disease. However, selenium supplementation had no effect on established Kashin-Beck disease, growth, or thyroid function once iodine deficiency was corrected. These results suggest that iodine, but not selenium, deficiency should be corrected in Tibetan children with Kashin-Beck disease.

Brick tea fluoride as a main source of adult fluorosis.

An epidemiological survey was conducted in Naqu County, Tibet in September 2001 to investigate the manifestations of fluorosis in adults caused by the habitual consumption of brick tea. Profiles were obtained for the total daily fluoride intake, environmental fluoride levels and average urinary fluoride concentration, and a physical examination and a skeletal radiographic study were conducted. One hundred and eleven 30-78-year-old adults were enrolled. It was found that the fluoride level of water sources in Naqu County was 0.10+/-0.03 mg/l; no evidence of fluoride air pollution was found, but the brick tea water processed foods--zamba and buttered tea--had fluoride contents of 4.52+/-0.74 mg/kg and 3.21+/-0.65 mg/l, respectively. The adult daily fluoride intake reached 12 mg, of which 99% originated from the brick tea-containing foods. The positive rate of clinical symptoms by physical examination was 89%; furthermore, 42 of the 111 subjects were diagnosed by X-ray. The positive examination rate was 83%. Although the osteosclerosis-type skeletal fluorosis (overall increased bone matrix density) affected 74%, arthropathy and arthritis affected a significant number of the patients, resulting in functional disability. The results suggest that this brick tea-type fluorosis had even more severe adverse effects on human health compared with both the water-type and coal combustion-type fluorosis that occurred in other areas of China.