Objective To find out the distribution of drinking-tea-borne fluorosis in the six ethnics in Qinghai Province, and to provide basic data for prevention and control of the disease. Methods In 2010, according to the requirement of “The National Surveillance Program of Drinking-Tea-borne Fluorosis”, six ethnics accounted for 99.59% of total population in Qinghai Province were investigated in 28 counties having brick-tea drinking habit. Three townships and a town in each county, two administrative villages(residents’ committee) in each township and town were chosen and 50 adults in each administrative village and residents ’ committee were selected to check skeletal fluorosis, dental fluorosis, urine fluoride and daily drinking amount of tea water. Five to six samples of drinking tea water were determined. Dental fluorosis was examined by Deans method; the fluoride content of brick-tea and urine were determined by fluoride ion selective electrode; the skeletal fluorosis was diagnosed based on “Endemic Osteofluorosis Clinical Indexing Diagnosis Standard”( WS 192-2008 ) . Results A total of 10 335 adults were surveyed, the number of Tibetan, Han, Hui, Mongolian, Tu and Salar ethnics were 4 972, 3 063, 1 196, 634, 235 and 235, respectively. The daily drinking amounts of tea water in Mongolian, Tibetan, Hui, Tu, Han and Salar ethnics were 2.53, 2.19, 1.74, 1.63, 1.22 and 1.07 L, respectively. Daily fluoride intakes in Tibetan, Mongolian, Tu, Hui, Han and Salar ethnics were 3.99, 2.78,2.27, 2.16, 1.78 and 1.28 mg, respectively. The medians of urinary fluoride concentration of the Tibetan, Tu, Hui, Han, Mongolian and Salar ethnics were 1.46, 1.19, 1.12, 0.98, 0.93 and 0.81 mg/L, respectively. The prevalence rates of dental fluorosis of the Hui, Han, Tibetan, Tu, Mongolian and Salar ethnics were 34.53%(413/1 196), 27.07%(829/3 063), 21.60%(1 074/4 972), 20.00%(47/235), 17.98%(114/634) and 6.38%(15/235), respectively. The incidence rates of clinical skeletal fluorosis of the Tibetan, Mongolian, Han, Hui, Tu and Salar ethnics were 13.42%(667/4 972), 11.04%(70/634), 9.31%(285/3 063), 7.61%(91/1 196), 5.53%(13/235) and 4.26%(10/235), respectively. Conclusions The distribution and prevalent status of drinking-tea-borne fluorosis in the six ethnics of Qinghai Province are different. Tibetan and Mongolian ethnics are the key population concerning the prevention and control of the disease.

Objective To investigate whether TG2 promotes drug resistance to epirubicin through AKT signal pathway in breast cancer. Methods MCF-7 cells with constant expression of TGM2 gene(TGM2-LV)were established via the lentiviral vector. The breast cancer cells were divided into five groups,including the NC group, TG2 group and MK2206 group. The MCF-7/adr cells were divided into ADR group and MKadr group. The expres-sion of TG2 ,AKT ,Bcl-2 and P53 was detected by Western blot assay. Cells were treated with epirubicin. MTT assay was performed to assess cell proliferation. The inhibition ratio of cancer cell proliferation was evaluated. TUNEL analysis was performed to identify the apoptosis of the breast cancer cells. Results Lvels of TG2,p-AKT and Bcl-2 in NC group were significantly lower than those in TG2 group,while the expression of P53 in NC group was much higher. In MK2206(or MK/adr )group,p-AKT and Bcl-2 were down-regulated,while P53 was markedly up-regulated compared with TG2(or ADR)group(P<0.05). The results of the MTT assay showed a strong inhibi-tion in cell proliferation rate in MK2206(or MKadr )group. Compared with the NC group,TG2 promoted prolifera-tion of MCF-7 cells in TG2 group. The cell apoptosis rate in MK2206(or MKadr )group was significantly higher than that in TG2(or ADR)group(P<0.05). TG2 significantly inhibit the apoptosis of breast cancer cells ,com-pared to the control group. Conclusion TG2 might promote drug resistance to epirubicin through AKT signal path-way in breast cancer

Objective:To understand the situation of drinking water-borne endemic fluorosis (short for drinking water fluorosis) in Huangzhong, Ping'an and Ledu districts of Qinghai Province and operation status of water improvement projects, and to evaluate the effect of control measures.Methods:In historical drinking water fluorosis villages of Huangzhong, Ping'an and Ledu districts of Qinghai Province in 2018, the status of water improvement, the operation of water improvement projects and the content of water fluoride were investigated; the dental fluorosis of 8-12 years old children in all investigated villages was checked; 3 villages from 3 districts were selected, X-ray examination for skeletal fluorosis and urinary fluoride detection of adults over 25 years old of age were performed.Results:Eight-two historical drinking water fluorosis villages in 3 districts were investigated and all the villages had water improvement projects, in addition, the water improvement projects were operating normally, and the water fluoride content ranged from 0.10 to 0.37 mg/L, which were in line with the drinking water fluoride content standard (< 1.2 mg/L). Totally 2 503 children aged 8-12 years old were examined, the detection rate of dental fluorosis was 6.03% (151/2 503), the index of dental fluorosis was 0.13, the epidemic intensity was negative; the detection rates of dental fluorosis in 3 districts were 6.24% (129/2 068), 4.05% (7/173), 5.73% (15/262), respectively, reaching the control standard (< 30%), and the detection rate of dental fluorosis in 81 villages was less than 30%; 198 adults over 25 years old were examined, the detection rate of skeletal fluorosis was 5.05% (10/198), the geometric mean of urinary fluoride was 0.81 mg/L, and skeletal fluorosis cases were mainly in the age group over 40 years old, all of them were mild cases.Conclusions:The fluoride content in drinking water and the detection rate of children's dental fluorosis are all up to the control standard, and the condition of skeletal fluorosis is significantly reduced after the implementation of water improvement measures in Huangzhong, Ping'an and Ledu districts. It can be seen that the prevention and control of drinking water fluorosis in Huangzhong, Ping'an and Ledu districts have achieved good results, but later management and condition monitoring of water improvement projects should be strengthened to prevent the disease from rebounding.

Objective To find out the distribution and status of drinking-water-borne fluorosis in Qinghai,and to provide basic data for prevention and control of the disease.Methods According to the "Action Plan of Endemic Fluorosis and Arsenic Poisoning in Qinghai (2016-2020)",10 counties were selected to carry out the epidemiological study in 2016.The operation of the improvment project was investigated.The fluoride content of water was determined with fluoride ion-selective electrode,and dental fluorosis of 8-12 years old children was diagnosed by the Deans method.Results A total of 97 villages have been investigated,and all water was improved.The range of water fluoride was 0.20-2.13 mg/L.Normal operation rate of water-improving project was 83.33％ (50/60).The pass rate of water fluorine content was 96.67％ (58/60).The prevalence rate of dental fluorosis of the children was 18.70％ (774/4 140),and it was significantly lower than national standards (30％).Conclusions Water has been improved in all of the fluorosis villages.Most of the water-improving engineering projects to control drinking-water fluorosis has played a positive role,and drinking-water-borne fluorosis is under control.

Objective To analyze the operation of water improvement projects in drinking water-borne fluorosis areas of Qinghai Province and the trend of dental fluorosis in children aged 8 to 12 years, and to evaluate the effects of prevention and control measures comprehensively, so as to provide basis for improving prevention and control strategies. Methods In 2009 - 2017, according to the "Qinghai Drinking Water Endemic Fluorosis Surveillance Program", four project counties of Huangyuan, Minhe, Hualong and Guide were selected in Qinghai Province. Three villages in each project county were selected according to their mild, moderate and severe conditions, and monitored the operation of water improvement projects, water fluoride content and dental fluorosis among children aged 8 to 12-year-old in each diseased village. Results In 2009-2017, the normal operation rate of water improvement projects increased from 2/8 to 7/8; the batch operation rate of the projects decreased from 5/8 to 1/8; the number of abandoned projects decreased from 1 to 0; the number of people covered by qualified water fluoride increased from 9962 to 80760 people; there was no significant difference in water fluoride content between different years (F = 0.758, P > 0.05). The total detection rate of children's dental fluorosis was 33.01％(1812/5489) from 2009 to 2017, the index of dental fluorosis was 0.65, and the epidemic intensity was slightly prevalent;the detection rate of children's dental fluorosis was 30.02％(951/3168) in villages with normal operation of water improvement projects and qualified water fluoride content, the index of dental fluorosis was 0.58, and the epidemic intensity was marginal;the detection rate of children's dental fluorosis was 32.72％(583/1782) in villages with abnormal operation of water improvement projects or excessive fluoride, the index of dental fluorosis was 0.66, and the epidemic intensity was slight; the detection rate of children's dental fluorosis in villages without changing the water was 51.58％ (278/539), and the index of dental fluorosis was 1.04, belonging to the moderate epidemic intensity; the detection rate of children's dental fluorosis in villages without changing the water was significantly higher than that in villages with normal operation of water improvement projects and qualified water fluoride content (χ2 = 102.30, P < 0.01). Conclusions The water improvement project in drinking water-borne fluorosis areas is running well and the operation rate is increasing year by year. The detection rate of dental fluorosis in children aged 8-12 years old in villages with normal operation of water improvement projects and qualified water fluoride content was significantly lower than that in villages without changing the water. The monitoring of fluorosis and the maintenance of water-renovation projects should be strengthened, and the problem of drinking water for residents in villages without changing the water should be resolved as soon as possible.

Objective To understand the epidemic situation of tea-drinking-borne fluorosis among children in Haixi Prefecture of Qinghai Province,and to provide basis for taking pertinent prevention and control measures.Methods In 2017,three townships (towns) were selected from five counties (cities) in Golmud,Delingha,Dulan,Ulan and Tianjun,Haixi,and one village (villages excluding excessive water fluoride) was selected from each township (town) as the investigation site.Fluoride content in drinking water,tea fluoride content and dental fluorosis in children aged 8-12 years were investigated.Water fluoride was determined using "Standard Test Method for Drinking Water" (GB/T 5750.5-2006);brick tea fluoride content was detected using "The Fluoride Content in Brick Tea" (GB 19965-2005);children's dental fluorosis was diagnosed using "Diagnosis of Dental Standard for Fluorosis"(WS/T 208-2011).Results Totally 75 drinking water samples were collected from each county (city).The water fluoride content ranged from 0.35 to 0.41 mg/L,with an average value of 0.37 mg/L,which was lower than the national drinking water fluoride standard of 1.00 mg/L.The fluoride content of 150 brick tea samples ranged from 206.0 to 796.0 mg/kg,with an average value of 629.8 mg/kg.A total of 1 325 children aged 8-12 were examined.The detection rate of dental fluorosis was 13.43％ (178/1 325),the index of dental fluorosis was 0.27,and the overall epidemic intensity was negative.The epidemic intensity in Dulan and Tianjun counties was marginal.There were significant differences in the detection rate of dental fluorosis among children of different ages (x2=35.26,P ＜ 0.05),and dental fluorosis was increased with ages in children.The detection rate of dental fluorosis in boys and girls was 13.31％ (90/676) and 13.56％ (88/649),respectively,with no significant difference (x2 =0.02,P ＞ 0.05).Conclusions There is an epidemic of tea-drinking-borne fluorosis among children in 5 counties (cities) of Haixi Prefecture.Although the epidemic is mild,it should not be ignored.Health education and publicity work for tea-drinking-borne fluorosis should be strengthened.

Objective To dynamic monitor drinking-water-borne fluorosis in Huzhu County and water improvement projects,to know the trend of the disease,and to evaluate the effect of prevention and control measures.Methods Seven townships in Huzhu County including 60 history drinking-water-borne fluorosis villages were selected as investigation sites in 2017,and demographic data were collected.In the villages of the diseased areas where the water had been changed,the operation of the water improvement project was investigated,and 1 tap water sample was collected to determine the fluorine content;for the villages in the diseased areas where the water had not been changed,one water sample was collected from the drinking water source in accordance with the five directions of east,west,south,north and middle to determine the fluorine content.More than 90％ of the children aged 8-12 years old in the surveyed villages were examined and judged for dental fluorosis.According to historical data,1 village with severe illness of children was selected,50 people were selected who were over 25 years old and lived in the villages for more than 5 years.Clinical and X-ray examinations of skeletal fluorosis were performed.Urine samples from adults surveyed were collected for urinary fluoride detection.Results Six of the 60 villages in the 7 townships had been relocated.By 2017,a total of 54 villages in drinking-water-borne fluorosis areas had changed their water.A total of 16 water improvement project were surveyed,among them,there were small water improvement project 6,accounting for 37.50％,large water improvement project 10,accounting for 62.50％;normal operated project 16,accounting for 100.00％;water fluoride content of qualified project 16,the qualified rate was 100.00％,the water fluoride content ranged 0.10-0.66 mg/L,covering a population of about 160 thousand and 846 people.A total of 2 399 children aged 8-12 were examined,117 cases of dental fluorosis were detected,the detection rate of dental fluorosis was 4.88％,dental fluorosis index was 0.13.Among them,89 cases were extremely mild,accounting for 3.71％ of all the children examined,21 cases were mild,accounting for 0.88％ of all the children examined,7 cases were moderate,accounting for 0.29％ of all the children examined,and no severe cases were found.A total of 68 adults over 25 years old were examined for skeletal fluorosis.Twelve patients were found to have clinical skeletal fluorosis.The detection rate was 17.65％.X-ray radiography was used to examine 46 people,and 1 case was detected,the detection rate was 2.17％.Clinical and X ray examinations showed no more than moderate patients.Fifty samples of adult urine were tested,the level of urine fluorine was 0.72 mg/L.Conclusions Water improvement project is working well in Huzhu County,and no serious children with dental fluorosis and adult skeletal fluorosis are detected.The prevention and control measures of drinking-water-bornefluorosis has achieved remarkable results in Huzhu County.We will continue to strengthen water improvement project and disease monitoring,and thoroughly control the prevalence of drinking water fluorosis.

Objective:To learn about the detection quality and external quality control assessment of fluoride and arsenic in laboratories at all levels in Qinghai Province.Methods:The Z-score method was used to analyze and evaluate the evaluation results of 1 provincial, 8 municipal and 43 county level laboratories of disease prevention and control institutions participating in the external quality control assessment of water fluoride and brick tea fluoride in Qinghai Province in 2021, as well as 1 provincial, 1 municipal and 2 county level laboratories of disease prevention and control institutions participating in the external quality control assessment of water arsenic and urine arsenic. The feedback rate and qualification rate of external quality control of each assessment laboratory were calculated.Results:In 2021, the feedback rate of external quality control of water fluoride, brick tea fluoride, water arsenic and urine arsenic in provincial and municipal level laboratories of Qinghai Province were 100.00%; except that the qualified rate of water fluoride was 7/9, the qualified rate of external quality control of other projects was 100.00%. The feedback rate of external quality control of water fluoride, brick tea fluoride, water arsenic and urine arsenic in county level laboratories was 100.00%; except that the qualified rate of water fluoride was 86.05% (37/43), the qualified rate of external quality control of other projects was 100.00%. In the specific assessment results of the laboratory, the assessment results of water fluoride sample FS20210101 from 1 provincial, 1 municipal and 2 county level laboratories, and FS20210102 from 1 county level laboratory were suspicious; the assessment results of water fluoride sample FS20210101 from 3 county level laboratories were not satisfactory; the assessment results of fluoride and arsenic sample in other laboratories were satisfactory.Conclusions:The qualified rate of external quality control of fluoride and arsenic in laboratories at all levels in Qinghai Province is relatively high, but some county level laboratories are still dissatisfied with the assessment results of water fluoride. Therefore, it is necessary to strengthen the detection level of water fluoride in laboratories.

Objective:To observe the changes of serum C-terminal peptide of type Ⅰ collagen (CTX-1) and N-terminal lengthening peptide of type Ⅰ collagen (P1NP) in adult patients with skeletal fluorosis in the tea-drinking-borne endemic fluorosis area in Qinghai Province, and to find sensitive indicators for diagnosis of skeletal fluorosis.Methods:From April to August 2019, a case-control study was carried out in tea-drinking-borne endemic fluorosis area in Zhiduo County, Yushu Tibetan Autonomous Prefecture, and Gangcha County, Haibei Tibetan Autonomous Prefecture of Qinghai Province. According to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008), the clinical diagnosis and X-ray examination of skeletal fluorosis were carried out for permanent residents ≥25 years old and living for more than 10 years in the area, combined with face-to-face inquiry and investigation of past disease history, lifestyle and clinical manifestations. The patients with skeletal fluorosis and healthy people were selected as skeletal fluorosis group and control group, respectively. Randomized urine samples and fasting venous blood from the two groups were collected. The content of fluoride in urine was determined by ion selective electrode method, and the contents of CTX-1 and P1NP in serum were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 127 people in the disease area were investigated, including 63 cases in skeletal fluorosis group and 64 cases in control group. There was no statistically significant difference in age and sex ratio between the two groups ( t = 0.42, χ 2 = 0.07, P > 0.05). The X-ray examination results showed that the patients with skeletal fluorosis were mainly mild, accounting for 71.43% (45/63); X-ray changes were mainly ossification of interosseous membrane and tendon. The urinary fluoride in control group and skeletal fluorosis group was 1.62 (1.12, 1.95) and 3.22 (2.38, 4.89) mg/L, respectively, with statistically significant difference between the two groups ( Z = 7.07, P < 0.001). The difference of serum CTX-1 and P1NP contents between the two groups was statistically significant ( Z = 2.00, 4.89, P < 0.05). Conclusions:The levels of serum CTX-1 and P1NP in patients with skeletal fluorosis are higher than those in healthy people. Serum CTX-1 and P1NP may be used as sensitive indicators for diagnosis of skeletal fluorosis.

Objective:To observe and evaluate the effect of health education on drinking brick-tea type fluorosis in Zhiduo County, Qinghai Province, so as to provide basis for further formulating health education strategies.Methods:From April 2019 to April 2020, according to the historical prevalence of drinking brick-tea type fluorosis in Zhiduo County, Qinghai Province, 3 townships (towns) were selected to carry out the health education activities on drinking brick-tea type fluorosis for students of grade 4 - 6, village doctors, adults and monks in each township (town). We carried out a one-year publicity on the prevention and treatment of drinking brick-tea type fluorosis, distributed health education materials and organized health education activities. Before and after the intervention, we conducted a questionnaire survey on health education among the target population (grade 4 - 6 students, village doctors, adults and monks), to evaluate the awareness rate and behavior formation rate of fluorosis prevention and control, and to evaluate the intervention effect.Results:A total of 86 students of grade 4 - 6, 40 village doctors, 42 adults and 20 monks were investigated, after the intervention, the awareness rates of prevention and treatment of drinking brick-tea type fluorosis in grade 4 - 6 students, village doctors, adults and monks were 87.98% (227/258), 96.67% (116/120), 81.75% (103/126), 83.33% (50/60), respectively, which were significantly higher than those before the intervention [38.38% (76/198), 83.33% (100/120), 15.45% (19/123), 28.89% (13/45), P < 0.05]. After the intervention, the behavior formation rates of prevention and treatment of the drinking brick-tea type fluorosis in grade 4 - 6 students, village doctors, adults and monks were 74.42% (128/172), 72.50% (58/80), 52.38% (44/84), 60.00% (24/40), respectively, which were significantly higher than those before the intervention [14.39% (19/132), 38.75% (31/80), 3.66% (3/82), 0(0/28), P < 0.05]. Conclusion:The comprehensive intervention measures based on health education can significantly improve the knowledge of local residents, and improve their bad drinking habits of drinking tea, which is of great significance to the prevention and treatment of drinking brick-tea type fluorosis.