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 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 verify the revised method of cerium sulfate catalytic spectrophotometry for iodide index of "Standard Examination Methods for Drinking Water-Nonmetal Parameters" (GB/T 5750.5-2006).Methods:From July to September 2019, the Laboratory of Department for Endemic Disease Prevention and Control of Qinghai Institute for Disease Prevention and Control verified the revised method (determination of iodide in drinking water by cerium sulfate catalytic spectrophotometry) of cerium sulfate catalytic spectrophotometry (hereinafter referred to as original method) in "Standard Examination Methods for Drinking Water-Nonmetal Parameters" (GB/T 5750.5-2006). The revised method was verified according to the requirements of "Standard Examination Methods for Drinking Water-Water Analysis Quality Control" (GB/T 5750.3-2006), including standard curve, detection limit, precision, accuracy and actual sample determination.Results:The linear range of the revised method was 0 - 20.0 μg/L, the correlation coefficient was - 0.999 4 - 0.999 8, and the detection limit was 0.231 μg/L. The relative standard deviation ( RSD) of low, medium and high iodine water samples of 6 times detection ranged from 1.4% to 9.6%, and the recoveries of low and medium water samples ranged from 89.0% to 108.0%. The detection results of national first-class reference materials for iodine composition analysis in water were within the range of standard value ± uncertainty. There was no significant difference in the test of results of 12 tap water samples between the revised method and the original standard method ( t = - 0.075, P > 0.05). Conclusion:The revised method has a good linear relationship of standard curve, high precision and accuracy, and good reproducibility, is simple and easy to operate, and is suitable for promotion and application.

Objective:To understand the changes of serum interleukin (IL)-2 and IL-6 in adult patients with Kashin-Beck disease (KBD) in Qinghai Plateau, and to provide scientific basis for scientific prevention and treatment of plateau KBD.Methods:According to the "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), adult KBD patients and healthy people over 18 years old were selected as KBD group and control group, respectively, in KBD disease areas of Xinghai County and Guide County, Hainan Tibetan Autonomous Prefecture, Qinghai Province. Fasting cubital venous blood was collected from the people of two groups, and the levels of serum IL-2 and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 193 people were surveyed, including 114 people in KBD group and 79 people in control group. There was no significant difference in age and sex ratio between the two groups ( t = 0.204, χ 2 = 2.547, P > 0.05). The serum IL-2 and IL-6 levels of the KBD group were (572.21 ± 172.92), (42.35 ± 15.86) pg/ml, respectively; compared with the control group [(511.28 ± 173.22), (51.96 ± 17.18) pg/ml], the differences were statistically significant ( t = 2.404, 3.999, P < 0.05). Conclusion:The serum IL-2 level is increased and IL-6 level is decreased in adult KBD patients in Qinghai Plateau, both of which may be involved in the inflammatory reaction of adult KBD.

Objective:To systematically evaluate the changes of serum nitric oxide (NO) content in adult patients with Kaschin-Beck disease (KBD).Methods:Systematic retrieval was conducted on China National Knowledge Infrastructure (CNKI), WanFang Data, VIP Database, PubMed, Embase and other databases, to analyze the literatures published from the database establishment to March 31, 2019, on the changes of serum NO content of adult patients with KBD. Meta-analysis was performed using Revman 5.3 software, and mean difference ( MD) and 95% confidence interval ( CI) were calculated; sensitivity analysis was performed using fixed-effect model or random-effect model based on heterogeneity results; and publication bias was evaluated using funnel chart. Results:Totally 7 qualified literatures were included, including 358 cases in the adult KBD group and 305 cases in the control group. After the heterogeneity test, there was heterogeneity among the literatures (χ 2 = 188.07, I2 = 97%, P < 0.01), so a random-effect model was used for Meta-analysis. The NO content in the KBD group was significantly higher than that in the control group (MD = 44.29, 95% CI: 30.57 - 58.00), the difference was statistically significant ( Z = 6.33, P < 0.01). Sensitivity analysis showed that the results of this study were stable. The two sides of the funnel were basically symmetrical, suggesting that the possibility of publication bias was small. Conclusion:The serum level of NO content in adult patients with KBD is significantly increased.

Objective To understand the changes of serum tumor necrosis factor-α (TNF-α) among adults with Kaschin-Beck disease (KBD) in Qinghai,and to provide scientific data for KBD prevention and control.Methods A case-control study was used,according to "Diagnosis of Kaschin-Beck disease",104 cases of KBD patients [aged (47.61 ± 12.72) years old;50 males,54 females] and 95 cases of internal healthy controls [aged (48.28 ±14.87) years old;35 males,60 females],which were from KBD areas in Xinghai and Guide counties of Hainan Tibetan Autonomous Prefecture,Qinghai Province,and 73 cases of external healthy controls [aged (51.88 ± 13.93)years old;35 males,38 females] from non-KBD region of Xunhua County were included in July 2017.Serum TNF-α was determined via the enzyme linked immunosorbent assay (ELISA) method.Results Totally 272 persons were studied and divided into three groups,there was no statistical significant difference of ages among the three groups (F =2.236,P ＞ 0.05),meanwhile,there was no statistical significant difference of genders among the three groups (x2 =3.135,P ＞ 0.05).The serum TNF-α levels of KBD patients,internal and external healthy controls were (25.14 ± 10.29),(21.84 ± 9.37),and (24.98 ± 8.98) ng/L,respectively,which were statistically significantly different among the three groups (F =3.486,P ＜ 0.05).The serum TNF-α levels in the KBD group and the external healthy control were higher than that in internal healthy control (P ＜ 0.05).There was no significant difference between the KBD group and the external healthy control (P ＞ 0.05).Conclusion There may exist inflammatory changes among KBD patients in KBD areas of Qinghai Province.

Objective To study the level of serum interleukin-1β (IL-1β) among adult patients with Kaschin-Beck disease (KBD) in the KBD area of Xinghai County,Qinghai Province.Methods In 2017,cluster random sampling was used to carry out investigation in the KBD area of Xinghai County,Hainan Tibetan Autonomous Prefecture,Qinghai Province,and the residents aged over 20 years old were selected as the survey subjects.According to "the Diagnosis Criteria of Kaschin-Beck Disease" (WS/T 207-2010),the subjects were divided into KBD group and the control group.The serum IL-1β content of the subjects was detected by enzymelinked immunosorbent assay (ELISA).Statistical analysis of data was performed using SPSS 17.0 software.Results A total of 188 eligible residents were surveyed,including KBD group (97 cases) and control group (91 cases).The age [(45.89 ± 11.75),(47.95 ± 11.75) years] and gender (male:48,38,female:43,59) of two groups were no statistically significant (t =1.050,x2 =3.485,P ＞ 0.05).The serum IL-1β levels of KBD patients and healthy control were (94.54 ± 24.19) and (65.95 ± 20.08) ng/L,respectively,which were significantly different (t =8.839,P ＜ 0.05).Conclusion There is an inflammatory change in adults with KBD in Xinghai County,Qinghai Province.

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 detect urinary bio-markers of hydroxyproline (HYP) and c-terminal telopeptide of collagen type Ⅱ (CTX-Ⅱ) among population from Kashin-Beck disease (KBD) regions in Qinghai Province,and to provide the scientific data for prevention and control of adult KBD.Methods According to the "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010),using case-control study,120 KBD patients (males 55,females 65) and 89 healthy controls (males 41,females 48) in Qinghai KBD regions were divided into case group and control group.Morning urine samples were collected.HYP and CTX-Ⅱ contents were analyzed by enzyme-linked immunosorbent assay (ELISA),then these results were corrected with creatinine.All the data were analyzed by SPSS 17.0 software.Results There was no significant difference in the age of male and female between case group and control group (t =1.813,1.131,P ＞ 0.05).The medians of urinary HYP and CTX-Ⅱ contents among male patients were 74.91 μg/μmol Cr and 630.77 ng/μmol Cr,respectively,which were higher than those of control groups (51.38 μg/μ mol Cr,401.32 ng/μmol Cr,Z =3.068,3.246,P ＜ 0.01).The medians of urinary HYP and CTX-Ⅱ contents among female patients were 91.07 μg/μmol Cr and 637.17 ng/μmol Cr,respectively,compared with those of control groups (88.37μg/μmol Cr,546.47 ng/μmol Cr),there was no significant difference in HYP content (Z =0.273,P ＞ 0.05),however,the difference in CTX-Ⅱ content was statistically significant (Z =2.002,P ＜ 0.05).Conclusion The urinary HYP contents of male patients with KBD change significantly,while the degradation of type Ⅱ collagen in male and female patients increases,and CTX-Ⅱ could reflect the metabolic changes of collagen in KBD.