Objective:To investigate the prevalence of adult skeletal fluorosis caused by drinking tea-type endemic fluorosis in Yushu Tibetan Autonomous Prefecture (hereinafter referred to as Yushu Prefecture), Qinghai Province, and provide scientific basis for prevention and control of the disease.Methods:In August 2021, one village was selected as a survey site in six counties (cities) in Yushu Prefecture, including Nangqian, Chindu, Yushu, Zadoi, Qumarlêb, and Zhiduo. Drinking water samples and 10 brick tea samples were collected from each village to determine the fluoride content in water and brick tea; at least 100 permanent residents aged ≥ 25, who had a habit of drinking brick tea and had lived in the local area for more than 5 years, were selected for X-ray imaging to examine the prevalence of adult skeletal fluorosis.Results:A total of 75 samples of residential drinking water were collected, with a fluoride content of (0.21 ± 0.05) mg/L, ranging from 0.11 to 0.34 mg/L; 60 samples of brick tea, with a fluoride content of (626.70 ± 157.27) mg/kg, ranging from 324.00 to 2 102.00 mg/kg. A total of 1 136 adults were examined, and 318 cases of skeletal fluorosis were diagnosed, with a detection rate of 27.99%. Among them, the detection rates of mild, moderate, and severe skeletal fluorosis were 20.95% (238/1 136), 6.07% (69/1 136), and 0.97% (11/1 136), respectively, with mild symptoms being the main. The detection rates of skeletal fluorosis in males and females were 29.09% (121/416) and 27.36% (197/720), respectively, with no statistically significant difference between the gender (χ 2 = 0.39, P = 0.533). Comparison of the skeletal fluorosis in different gender, the differences were statistically significant (χ 2 = 22.31, P < 0.001). The detection rates of skeletal fluorosis in the age groups of 25 - 35, 36 - 45, 46 - 55, 56 - 65, 66 - 75, and ≥76 years old were 6.86% (7/102), 22.37% (51/228), 24.02% (92/383), 37.44% (73/195), 43.48% (70/161), and 37.31% (25/67), respectively. The differences between the groups were statistically significant (χ 2 = 59.84, P < 0.001). Moreover, there was a statistically significant difference in the composition of skeletal fluorosis among different age groups ( H = 37.66, P < 0.001). The Spearman correlation analysis results showed that the severity of adult skeletal fluorosis was positively correlated with age ( r = 0.34, P < 0.001). Conclusions:There is a certain degree of prevalence of adult skeletal fluorosis in Yushu Prefecture. And as age increases, the condition of skeletal fluorosis becomes more severe.

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 follow up the iodine nutrition and intellectual development of school children aged 8-10 years old in Nangqian County of Qinghai Province after 9 years of the implementation of iodine deficiency disorders intervention measures with iodine supplement as the main measure.Methods:In order to improve the iodine nutritional status of the population in Nangqian County, free iodized salt distribution, health education and other intervention measures for iodine deficiency disorders were implemented for 9 consecutive years since 2013. In May 2012 (before iodine supplementation) and September 2021 (after iodine supplementation), the same 5 townships (towns) were selected, and children aged 8-10 years old (half male and half female, age balanced) born locally in the central primary school of each township (town) were selected as the survey subjects. Household edible salt samples and random urine samples were collected for salt iodine and urinary iodine detection; the second revised version of the Chinese Combined Raven's Test (rural version) was used to assess the intelligence quotient (IQ) of children. The Flynn effect (FE) gain was used to adjust IQ, the corrected IQ = (IQ starting point value - current year's IQ value) - FE gain (calculated by 0.74/year). The differences of salt iodine and urinary iodine related indexes, IQ value and corrected IQ were compared before and after iodine supplementation.Results:After iodine supplementation, the coverage rate of iodized salt reached 100.00% (300/300), and the consumption rate of qualified iodized salt reached95.00% (285/300), the median urinary iodine increased to 157.20 μg/L, and all indexes met the elimination standard of iodine deficiency disorders. The IQ value of children aged 8-10 years old after iodine supplementation was 99.00 ± 14.90, significantly higher than that before iodine supplementation (82.00 ± 13.20, F = 156.82, P < 0.001). The FE gain in 9 years was 6.66, and the actual IQ gain of children aged 8-10 years old after iodine supplementation was 10.34. There were statistically significant differences in IQ value before and after iodine supplementation in male and female children ( F = 78.84, 78.88, P < 0.001). After iodine supplementation, there was a statistically significant difference in IQ value between children in the 8-year-old group and the 10-year-old group ( P = 0.010). There were statistically significant differences in IQ value before and after iodine supplementation in 8, 9 and 10 years old groups ( F = 55.23, 65.79, 36.85, P < 0.001). Conclusion:Intervention measures for iodine deficiency disorders, mainly iodine supplement, can significantly improve the iodine nutrition status of children aged 8-10 years old, and significantly promote the intellectual development of children.

Objective:To evaluate the water fluoride detection ability of county (city, district) level (referred to as the county-level) laboratories in Qinghai Province.Methods:During the "13th Five-Year Plan" period (2016 - 2020), 4, 4, 4, 43, 43 county-level laboratories in Qinghai Province were organized to participate in the national water fluoride external quality control assessment, and the assessment results were evaluated by Z-ratio scoring method.Results:The response rate of county-level laboratories was 86.05% (37/43) in 2019, and 100.00% in other years. The qualified rate of county-level laboratories was 100.00% from 2016 to 2018; in 2019 and 2020, the assessment was fully covered, and the qualified rate was 81.40% (35/43) and 95.35% (41/43), respectively. Compared with 2019, the response rate and qualified rate in 2020 increased significantly, and the differences were statistically significant (χ 2 = 6.450, 4.074, P < 0.05). In the past 5 years, two assessment samples│Z│ < 1 in each laboratory were the most common, but with two assessment samples 2≤│Z│ < 3 in some qualified laboratories. Conclusion:The consistency of water fluoride determination in Qinghai Province is not very ideal, and the detection ability of county-level laboratories still needs to be strengthened.

Objective:To analyze the external quality control assessment results of fluoride in brick tea in the provincial, city (prefecture) and county (city, district)-level endemic fluorosis laboratories in Qinghai Province, and to evaluate the testing capabilities of laboratories at all levels.Methods:The Z-score method was used to analyze and evaluate the results of provincial, city (prefecture) and county (city, district)-level laboratories that participated in the external quality control assessment of fluoride in brick tea in Qinghai Province from 2014 to 2020, and│Z│≤2 was qualified; 2 <│Z│ < 3 was basic qualified; │Z│≥3 was unqualified.Results:From the feedback, the feedback rate of external quality control of fluoride in brick tea in provincial and city (prefecture)-level laboratories in Qinghai Province from 2014 to 2020 was 100.00%; the feedback rate of county (city, district)-level laboratories from 2014 to 2018 was 100.00%, and there were no feedback units in 2019 and 2020. From the assessment of qualification, the qualification rate of provincial, city (prefecture)-level laboratories was 100.00% in all other years except one unit failed in 2017; the qualification rate of county (city, district)-level laboratories was 100.00% in 2014, 2015, 2016 and 2019, and there were 6 unqualified units in other years.Conclusions:From 2014 to 2020, some endemic fluorosis laboratories in Qinghai Province still fail to pass the external quality control assessment of fluoride in brick tea. In the future, it will be the focus of work to strengthen personnel training and improve the detection ability.

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 study the epidemic status of drinking tea type endemic fluorosis in Qinghai Province.Methods:In 2019, in counties (cities, districts, referred to as counties) that had the habit of drinking brick tea in 8 cities (prefectures) of Qinghai Province, epidemiological investigation of drinking tea type endemic fluorosis was carried out in villages. Ten households were randomly selected from each village, to investigate the demographic data of each household and the drinking situation of brick tea, residents' drinking water and brick tea samples were collected to determine the fluorine content, and calculate the daily per capita tea fluorine intake. At the same time, skeletal fluorosis was examined in all adults over 25 years old, and dental fluorosis was examined in all children aged 8 to 12 years old in survey sites. The content of fluorine in tea and water was detected by ion selective electrode method; the diagnosis of skeletal fluorosis was based on "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008), the diagnosis of dental fluorosis was based on "Diagnosis of Dental Fluorosis" (WS/T 208-2011).Results:The mean (range) of fluorine of the 3 602 water samples was 0.31 (0.20 - 1.00) mg/L. The geometric mean (range) of fluorine of the 31 067 brick tea samples was 646 (40 - 2 295) mg/kg, the fluorine content of the brick tea ≤300 mg/kg accounted for 7.80% (2 422/31 067) of the total samples. The proportion of drinking Fu brick-tea was 89.97% (27 952/31 067); and the daily per capita tea fluorine intake was 1.93 mg, the daily per capita tea fluorine intake in Guoluo, Yushu and Hainan prefectures were higher than the health standard (3.50 mg). The detection rate of skeletal fluorosis in adults was 0.16% (2 357/1 484 907), Yushu Prefecture was the highest [29.23% (592/2 025)], followed by Guoluo Prefecture, which was 8.21% (771/9 393). The detection rate of dental fluorosis in children was 4.79% (8 076/168 623), Yushu Prefecture was the highest [32.61% (1 562/4 790)].Conclusion:Drinking tea type endemic fluorosis is prevalent in Qinghai Province, with obvious regional characteristics, covering a large population. The disease is relatively popular in Yushu Prefecture and Guoluo Prefecture.

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.

Objective:To comprehensively evaluate the correlation between migraine and the risk of hemorrhagic stroke using Meta-analysis.Methods:The published observational studies on migraine and the risk of hemorrhagic stroke in PubMed, EMbase, Cochrane library, Chinese Biomedical Database, China Journal Full-text Database, Wanfang Database and VIP Database were retrieved by computers. The retrieval time limit was from the establishment of the databases to December 31, 2019. Two reviewers independently conducted the literature screening and data extraction, and evaluated the quality according to Newcastle Ottawa scale. Stata SE 12.1 software was used for Meta-analysis.Results:Six case-control studies and 7 cohort studies met the inclusion criteria, all of which were in English. The results of Meta-analysis showed that exposure to migraine increased the risk of hemorrhagic stroke (odds ratio [ OR] 1.47, 95% confidence interval [ CI] 1.23-1.76; P<0.001). Sensitivity analysis showed that the results were robust. Subgroup analysis showed that migraine with aura ( OR 1.38, 95% CI 1.05-1.81; P=0.019), migraine without aura ( OR 1.46, 95% CI 1.19-1.80; P<0.001), male ( OR 2.10, 95% CI 1.72-2.56; P<0.001) and female ( OR 1.53, 95% CI 1.22-1.92; P<0.001) migraine could increase the risk of hemorrhagic stroke. Conclusion:Regardless of the gender of patients and presence or absence of migraine aura, migraine can significantly increase the risk of hemorrhagic stroke.