Objective To analyze the epidemiological characteristics and epidemic situation of children with Kashin-Beck disease (KBD) in China,and provide the basis for formulating prevention and control measures. Methods Fixed-point monitoring,moving-point monitoring,and full coverage of monitoring were promoted successively from 1990 to 2023. Some children (7-12 years old) underwent clinical and right-hand X-ray examinations every year. According to the KBD diagnosis criteria,clinical and X-ray assessments were used to confirm the diagnosis. Results In 1990,the national KBD detectable rate was 21.01％. X-ray detection decreased to below 10％ in 2003 and below 5％ in 2007. Between 2010 and 2018,the prevalence of KBD in children was less than 0.4％,which fluctuated at a low level,and has decreased to 0％ since 2019. Spatial epidemiological analysis indicated a spatial clustering of adult patients prevalence rate in the KBD areas. Conclusion The evaluation results of the elimination of KBD in China over the last 5 years showed that all villages in the monitored areas have reached the elimination standard. While the adult KBD patients still need for policy consideration and care.

Objective:To analyze the external quality control assessment results of fluoride testing laboratories in endemic disease prevention and control institutions nationwide from 2006 to 2023, investigate the quality control capabilities of these laboratories in various provinces, prefectures, cities, and counties nationwide, and ensure the accuracy and reliability of surveillance data on endemic fluorosis nationwide.Methods:Using retrospective analysis, the external quality control assessment results of all participating fluoride testing laboratories of national endemic disease prevention and control institutions from 2006 to 2023 were summarized and analyzed. The assessment results from 2006 to 2008 were tested for outliers using Grubbs method, homogeneity of variance using Cochran method, excluding the assessment data of unqualified laboratories, calculating the total mean and total standard deviation, Z-score method was used to test the assessment of laboratories, and statistical analysis and judgment were done when the result of │Z│ < 3. The assessment results from 2009 - 2023 were obtained from all laboratories. In 2010, two tests were conducted in the first and second half of the year, and the Z-ratio scores of each laboratory were calculated using robust statistics. When │Z│≤2, the assessment was qualified; when 2 < │Z│ < 3, the assessment was basically qualified; when│Z│≥3, the assessment was unqualified, and the consensus value came from all participating laboratories in the assessment.Results:From the beginning of quality control operation in 2006 to 2023, the number of laboratories participated in external quality control assessments had significantly increased. The number of laboratories participated in water fluoride assessment increased from 30 in 2006 to 1 277 in 2023, and the number of laboratories participated in urine fluoride assessment increased from 29 to 497. The number of laboratories participated in the brick tea fluorine assessment had increased from 43 in 2014 to 193 in 2023. The assessment results showed that when │Z│ < 3, the total qualified rate of fluoride external quality control in fluoride testing laboratories of national endemic disease control institutions was 95.2%, with the lowest being 87.1% (27/31) in 2008 and the highest being 100.0% (394/394) in 2014. When │Z│≤2, the total feedback pass rate was 88.4%, with the lowest being 79.3% (288/363) in the first half of 2010 and the highest being 99.5% (392/394) in 2014. The assessment results showed that when │Z│ < 3, the total pass rate of urine fluoride external quality control in fluoride testing laboratories of national endemic disease control institutions was 98.0%, with the lowest being 86.2% (25/29) in 2006 and 2007, respectively, and the highest being 100.0% (68/68) in 2014. When │Z│≤2, the total qualification rate was 93.7%, with the lowest being 86.5% (64/74) in the second half of 2010 and the highest being 100.0% (68/68) in 2014. The assessment results showed that when│Z│ < 3, the total pass rate of extra-fluoride quality control of brick tea in fluoride testing laboratories of national endemic disease control institutions was 95.4%, with the lowest being 85.0% (164/193) in 2023, and the highest being 100.0% (43/43, 51/51, 79/79) in 2014, 2015 and 2016, respectively. When │Z│≤2, the total pass rate was 89.2%, with the lowest being 72.7% (32/44) in 2017 and the highest being 100.0% (43/43) in 2014. From 2009 to 2023, there were a total of 21 provincial-level laboratories that passed the water fluoride detection assessment, including 3 provinces where all prefecture level and county-level laboratories were qualified. The assessment results of urinary fluorine showed that there were 11 qualified provincial-level laboratories and 1 prefecture-level laboratory. From 2014 to 2023, the assessment results of brick-tea fluorine showed that there were 5 provincial-level laboratories that passed the tea fluorine testing assessment and no prefecture-level laboratory.Conclusions:Conclusion: From 2006 to 2023, the number of fluoride testing laboratories participating in external quality control assessment has increased year by year, and most provincial, municipal and county-level laboratories have good fluoride testing capabilities, which can meet the testing needs of endemic disease prevention and monitoring. For some laboratories with problems, targeted rectification should be carried out to improve the quality of detection, in order to provide better technical support for the monitoring of endemic fluorosis areas.

Over the past decade, remarkable progress has been made in prevention and control of endemic diseases in China through implementation of the 12th and the 13th Five-Year National Plans for Prevention and Control of Endemic Diseases and the Three-Year Action Plan for Special Prevention and Control of Endemic Diseases. Based on the latest monitoring data of endemic diseases and the evaluation results of the control and elimination of endemic diseases of the 13th Five-Year Plan, this paper analyzed current main problems in prevention and control of endemic diseases in China, focusing on implementation of prevention and control measures for iodine deficiency disorders, endemic fluorosis, and endemic arsenicosis, as well as the treatment and management of patients. Accordingly, corresponding countermeasures and suggestions are put forward from three aspects, including prevention and control mechanism, implementation of prevention and control measures, and scientific research, so as to provide scientific basis for the country and various regions to consolidate the achievements of prevention and control of endemic diseases and accurately implement the prevention and control measures of endemic diseases.

Objective:To investigate the dynamic prevalence of Kashin-Beck disease (KBD) in 2020, and to provide the basis for assessment of KBD control and elimination.Methods:According to the "Kashin-Beck Disease Monitoring Plan (2019 Edition)", collection of basic information of endemic areas and children KBD examination were executed in all endemic areas from every endemic county (city, district, banner) of 13 endemic provinces. All children aged 7 - 12 years in endemic areas underwent clinical examination, X-ray examination was performed for clinically positive children. According to the criteria of "Diagnosis of Kashin-Beck Disease" (WS/T 207-2010), KBD cases were diagnosed by both clinical examination and X-ray check.Results:In monitoring of 827 986 children of 7 - 12 years old, a total of 703 children with similar clinical signs of KBD were suspected positive cases. X-ray results showed that 703 children were normal, with no X-ray positive change, they were not children KBD cases.Conclusions:In 2020, no cases of Kashin-Beck disease are detected in children nationwide, and the condition of Kashin-Beck disease in children nationwide continues to be at a level of elimination.

In the past 10 years, remarkable progress has been made in prevention and control of endemic diseases in China through implementation of the National Plan for Prevention and Control of Endemic Diseases during the "12th Five Year Plan" and the "13th Five Year Plan" and the Three-year Action Plan for Tackling Key Problems in Prevention and Control of Endemic Diseases. Based on analysis of the monitoring data of endemic diseases in China for 10 consecutive years, this paper summarized the progress made in prevention and control of endemic diseases in China, discussed the main problems faced at present, and put forward key tasks of prevention and control of the diseases in the future.

Objective:To master the status of Kashin-Beck disease (KBD) in 2019, to provide the basis for assessment of KBD control and elimination.Methods:Data of endemic areas basic information collection and children KBD examination were executed in all endemic villages from every endemic county (city, district, banner) of 13 endemic provinces. All children aged 7 - 12 years in endemic villages underwent clinical examination, and X-ray examination was performed for clinically positive children. When both the clinical examination and X-ray reexamination were positive, the diagnosis was KBD.Results:In monitoring of 823 365 7 - 12 years old children, a total of 3 057 children with similar clinical signs of KBD were suspected positive cases. The results of X-ray reexamination showed that the X-ray manifestations of 3 057 children were normal, and no X-ray positive changes were found, that is, there was no case of KBD in children. A total of 16 559 endemic villages in 13 endemic provinces were monitored, and all reached the criteria for KBD elimination. Surveillance of all endemic villages was completed except Tibet Autonomous Region, the KBD elimination rates of endemic villages were 100.00% in 12 endemic provinces and 99.01% (16 559/16 725) in all 13 endemic provinces.Conclusions:No children KBD case is detected in 2019, children KBD stays at its eliminating level throughout the country. And 100.00% endemic villages meet the criteria for KBD elimination in the remaining 12 endemic provinces except Tibet Autonomous Region.

Objective:To investigate the oral medication treatment of adult patients with Kashin-Beck disease(KBD) in China, so as to provide theoretical basis for medication screening of KBD and to provide scientific guidance for clinical treatment of KBD.Methods:Based on the "Endemic Disease Prevention and Control Project of Special Funds for Local Public Health Subsidized by the Central Government" and "Major Public Health Service Endemic Disease Prevention and Control Project", the treatment information of adult patients with KBD in 11 provinces (autonomous regions, referred to as provinces) in China from 2006 to 2017 was collected, and the treatment coverage of adult patients with KBD in different years and regions was analyzed, and the curative effect of patients with different severity was evaluated.Results:From 2006 to 2017, the number of provinces participating in the treatment project was from 2 to 11. The actual total number of people treated in China was 68 061, with a completion rate of 78.10% (68 061/87 149); the annual number of people treated increased linearly; the overall clinical symptom remission rates of adult patients with KBD in all regions reached more than 50%, and the overall treatment effect showed an upward trend year by year; compared with patients with grade Ⅲ, after oral medication, the remission rates of clinical symptoms in patients with gradeⅠandⅡ were higher (the average remission rate of clinical symptoms was 84.13% for gradeⅠ, 80.71% for grade Ⅱ and 72.11% for grade Ⅲ, P < 0.05). Conclusions:Oral medication treatment can effectively alleviate the clinical symptoms of most adult patients with KBD of grade Ⅰ and Ⅱ. Patients of grade Ⅲ should be considered treating with oral medication combined with other treatment methods. A considerable number of patients are still ineffective in taking drugs at this stage, and it is urgent to carry out the screening, research and development of specific medications for KBD.

Objective To investigate the effects of fluoride on protein oxidative damage in rat plasma by measuring oxidative stress levels,advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP).Methods Eighty SPF male 3-week-old Wistar rats weighing (82.34 ± 10.60) g were randomly divided into 4 groups,20 rats in each group.The control group drank distilled water,and the fluoride groups drank distilled water with fluoride concentrations of 25,50 and 100 mg/L,respectively.Rats were allowed to eat and drink freely,and they were sacrificed at 1 month and 3 month,respectively,and samples such as urine,femur and peripheral blood were collected for experiments.Fluoride contents in urine and bone were detected by ion selective electrode method,the superoxide dismutase (SOD) activity was detected by hydroxylamine method,malondialdehyde (MDA) content was detected by thiobarbituric acid (TBA) method,and AGEs and AOPP contents were detected by enzyme linked immunosorbent assay (ELISA).Results For 1 month and 3 months,compared urinary fluoride contents (mg/L:2.088 + 0.638,9.170 ± 2.865,20.094 ± 8.186,54.866 ± 2.866;2.202 ± 1.282,9.112 ± 2.364,21.854 ±8.325,52.513 ± 16.211),and bone fluoride contents (mg/kg:324.985 ± 127.094,846.148 ± 331.861,1 886.601 ±250.140,2 420.971 ± 135.883;417.591 ± 88.324,1 582.243 ± 347.975,2 163.519 ± 614.932,2 755.434 ±265.370) in control group and fluoride concentrations of 25,50 and 100 mg/L groups,the differences were statistically significant (F =88.379,29.225;87.440,33.998,P ＜ 0.05).For 1 month and 3 months,compared SOD activity (U/ml:32.469 ± 5.674,35.931 ± 2.262,36.746 ± 3.994,38.042 ± 4.632;31.027 ± 4.147,30.777 ±4.791,34.148 ± 1.755,36.585 ± 2.860) and AGEs contents (μg/L:26.977 ± 5.285,33.303 ± 6.226,28.021 ±5.946,34.117 ± 6.706;35.681 ± 3.802,33.651 ± 7.214,28.114 ± 4.660,24.330 ± 3.581) in control group and fluoride concentrations of 25,50 and 100 mg/L groups,the differences were statistically significant (F =2.896,5.780;3.565,10.195,P ＜ 0.05).By factorial design anova,there was an interaction between the exposure concentration and exposure time of fluorine and the content of AGEs (F =8.957,P ＜ 0.01).Conclusion Excessive fluoride can affect urinary,bone fluoride contents,SOD activity,AGEs content,suggesting that excessive fluoride may regulate protein expression through direct and indirect oxidative damage pathways,which leading to fluorosis.

Objective To investigate the effects of fluoride exposure dose and exposure time on the expression of 5-methylcytosine (5-mC) in blood,liver,kidney and brain of rats;and to understand whether there is a difference in the effects of fluoride on DNA methylation levels in different tissues.Methods Eighty three-week old SPF male Wistar rats were randomly divided into four groups according to body weight [(82.34 ± 10.60) g],with 20 rats in each group.The rats of control group drank distilled water and the fluoride group's drank distilled water containing 25,50 and 100 mg/L of F ion,respectively.Rats were sacrificed after fed for 1 month and 3 months (n =10),and peripheral blood and tissue samples were collected.The incidence of dental fluorosis was observed in rats.Bone and urine fluoride content was detected by ion selective electrode method.The content of 5-mC in blood,liver,kidney and brain was detected by enzyme-linked immunosorbent assay (ELISA).The independent and interactive effects of fluoride exposure dose and exposure time on 5-mC in rat peripheral blood and different tissues were analyzed by factorial design anova.Results After feeding for 1 month and 3 months,all rats in the fluoride group had dental fluorosis with different severities,while none dental fluorosis was found in the control groups.Fluoride exposure dose and exposure time had a main effect on bone fluoride contents [1 month:(324.985 + 127.094),(846.148 ± 331.861),(1 886.601 + 250.140),(2 420.971 + 135.883) mg/kg;3 months:(417.591 ± 88.324),(1 582.243 ± 347.975),(2 163.519 ± 614.932),(2 755.434 ± 265.370)mg/kg;F =96.692,13.077,P ＜ 0.01],respectively,but there was no interaction effect (F =2.013,P ＞ 0.05);fluoride exposure dose had a main effect on urinary fluoride contents (F =62.358,P ＜ 0.01),the exposure time had no effect on it (F =0.862,P ＞ 0.05),and there was no interaction effect (F =0.081,P ＞ 0.05).Fluoride exposure dose had a main effect on the 5-mC content in the blood (F =8.446,P ＜ 0.01),the exposure time had no effect on it (F =0.095,P ＞0.05),and there had an interaction effect (F =4.676,P ＜ 0.01).Fluoride exposure dose and exposure time had a main effect on the 5-mC content in the liver,respectively (F =4.737,7.064,P ＜ 0.01 or ＜ 0.05),and an interaction effect was exist (F =8.302,P ＜ 0.01).Fluoride exposure time had a main effect on the 5-mC content in the kidney (F =6.340,P ＜ 0.05),the exposure dose had no effect on it (F =0.140,P ＞ 0.05),and there was no interaction effect (F =1.269,P ＞ 0.05).Fluoride exposure dose and exposure time had no effect on 5-mC content in the brain (F =0.633,2.065,P ＞ 0.05).Conclusion Fluoride exposure dose and exposure time have the different effect on the levels of 5-mC in blood,liver,kidney and brain,suggesting that there may be differences in the effects of fluoride on DNA methylation levels in different tissues.

Objective To investigate the effect of fluoride on osteoclast in bone tissue of rats and its mechanism.Methods Twenty specific pathogen free male Wistar rats aged 3 weeks were randomly divided into two groups by weight (each group has 10).The rats of control group drink distilled water and treatment group drink distilled water containing 100 mg/L fluoride.The rats were fed for 3 month.The dental fluorosis in rats was observed.The ion selective electrode method was used to measure bone fluoride accumulation.The pathological changes of bone tissue in rats were observed under light microscope.The osteoclast was identified by tartrateresistant acid phosphatase (TRAP) staining.The calcineurin (CaN) activity of serum was measured by detection of free phosphate with malachite green.The bicinchoninic acid (BCA) method was used to detect total protein concentration of serum.The colorimetry method was used to detect calcium and malondialdehyde (MDA) levels in serum.The enzyme linked immunosorbent assay (ELISA) method was used to detect calmodulin (CaM) content.Results By the end of the experiment,none dental fluorosis was detected in control group,all rats in fluoride group had dental fluorosis.The bone fluoride content of rats in fluoride group [(4 460.671 ± 418.548) mg/kg] was about 7.6 times higher than that in control group [(582.534 ± 58.342) mg/kg,t =-29.020,P ＜ 0.01].Compared with the control group,the bone tissue of rats in fluoride group showed thicker bone trabecular,sclerotin fusion and incomplete mineralization.Positive signal intensity of TRAP staining of bone tissue in fluoride group was significantly higher than that in control group.The number of osteoclast formation in fluoride group [10 (5-12)] was significantly higher than that in control group [3 (2-4);U =92.5,P ＜ 0.01].CaN activity in serum of rats in fluoride group [(3.334 ± 0.654) nmol/mg prot] was significantly higher than that in control group [(1.289 ± 0.361) nmol/mg prot;t =-6.346,P ＜ 0.01].The Ca and CaM content of serum in rats were not significantly different between the two groups.However MDA content in fluoride group [(7.703 ± 2.954) μmol/L] was significantly higher than that in control group [(3.958 ± 1.965) μmol/L,t =-2.968,P ＜ 0.05].Conclusion Excessive fluoride may increase osteoclast formation in bone tissue of rats,and the mechanism might be fluoride stimulated CaN activity through oxidative stress pathway.