Objective:To gain a understanding of the occurrence of cognitive impairment among residents in drinking water-borne endemic fluorosis (drinking water-borne fluorosis) areas, and to study its influencing factors.Methods:In March 2023, a cluster sampling method was used to select local residents aged 18 and above from the drinking water-borne fluorosis areas in Jishan County, Shanxi Province as survey subjects. General demographic data were collected through face-to-face surveys, and a random urine sample was collected once to determine urinary fluoride level. Cognitive function was assessed using the mini-mental state examination (MMSE), and the survey subjects were divided into a cognitive impairment group ( < 27 points) and a control group (27 - 30 points) based on the MMSE scores. A multiple logistic regression model and a decision tree model based on chi-squared automatic interaction detector were constructed to analyze the factors affecting cognitive impairment, and the model fitting effect was evaluated using receiver operating characteristic (ROC) curve.Results:A total of 3 301 subjects were included in the survey, including 2 081 females and 1 220 males. There were 1 515 subjects < 60 years old and 1 786 subjects ≥60 years old, with urinary fluoride level [ M ( Q1, Q3)] of 2.92 (1.78, 4.54) mg/L. There were 1 939 cases in the cognitive impairment group and 1 362 cases in the control group, with a detection rate of 58.74% (1 939/3 301) for cognitive impairment; and the differences in gender, age, education level, marital status, annual household income, alcohol consumption, smoking distribution, and urinary fluoride level between the two groups were statistically significant ( P < 0.05). The results of multiple logistic regression analysis showed that female, ≥60 years, and urinary fluoride > 4.54 mg/L were risk factors for cognitive impairment [ OR (95% CI): 1.25 (1.01, 1.54), 2.66 (2.26, 3.14), 1.32 (1.06, 1.65), P < 0.05]. Education level of primary school or above, annual household income≥12 000 yuan, and mild alcohol consumption were protective factors for cognitive impairment [ OR (95% CI): 0.15 (0.09, 0.25), 0.58 (0.48, 0.68), 0.67 (0.51, 0.87), P < 0.05]. The analysis results of the decision tree model showed that age had the greatest impact on the occurrence of cognitive impairment, followed by annual household income, education level, and urinary fluoride. The areas under the ROC curves of the multiple logistic regression and decision tree model were 0.72 and 0.70 ( P < 0.001), respectively, indicating good model fitting performance. Conclusion:The detection rate of cognitive impairment in residents of drinking water-borne fluorosis areas is relatively high, and age, annual household income, education level, and urinary fluoride are all influencing factors for occurrence of cognitive impairment.

Objective:To study the impact of fluoride exposure through drinking water on the risk of hypertension among residents in Jishan County, Shanxi Province.Methods:From March to April 2023, a cluster sampling method was used to select permanent residents aged ≥18 years and residing for ≥10 years in 12 villages in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province as the survey subjects. A questionnaire survey, physical examination, and morning urinary fluoride level testing were conducted. The least absolute shrinkage and selection operator (Lasso) regression were used to analyze the key influencing factors of hypertension. Restricted cubic spline was used to evaluate the linear relationship between urinary fluoride and hypertension. Logistic regression was used to analyze the impact of urinary fluoride on hypertension.Results:Finally, 2 453 survey subjects were included, aged (62 ± 10) years, including 1 565 patients (63.80%) with hypertension. There were significant differences in the distribution of age, gender, education level, annual household income, body mass index (BMI), and the level and distribution of urinary fluoride between hypertension group and normal blood pressure group ( P < 0.05). The Lasso regression results showed that age, education level, BMI, and urinary fluoride were the key influencing factors of hypertension, with coefficients of 1.04, - 0.12, 0.24 and 0.01, respectively. The results of the restricted cubic spline showed that there was a linear relationship between urinary fluoride and hypertension after adjusting for age, education level, and BMI ( Poverall = 0.018, Pnonlinear = 0.482). The logistic regression results showed that after adjusting for age, education level, and BMI, urinary fluoride > 4.68 mg/L was a risk factor for hypertension ( OR = 1.42, 95% CI: 1.10 - 1.84, P = 0.007). Conclusion:High urinary fluoride is a risk factor for hypertension in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province.

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

Objective:To analyze the effects of fluorine exposure on calcium ion metabolism and the expression of related calcium-regulating proteins in the kidneys of rats.Methods:Forty-five 5-week-old specific pathogen-free male Wistar rats (weighed 90 - 120 g) were selected and divided into three groups according to the randomized numeric table: 0 (control), 50, and 100 mg/L fluorine exposure groups, with 15 rats in each group. The control group was given deionized water, while the 50 and 100 mg/L fluorine exposure groups were given sodium fluoride solutions containing 50 and 100 mg/L fluorine ions, respectively. After 12 weeks, urine samples were collected, and kidneys and blood were harvested. Urinary fluorine levels were measured using a fluoride ion-selective electrode method. Calcium ion levels in the urine, kidneys, and serum were determinated using the methylthymol blue microplate method. The protein expression levels of transient receptor potential vanilloid receptor 5 (TRPV5), calbindin-D28K (CB-D28K), sodium-calcium exchanger-1 (NCX1), Klotho and plasma membrane calcium ATPase 1b (PMCA1b) in the kidneys were detected by Western blotting and immunohistochemistry.Results:The urinary fluorine levels in the control group and the 50 and 100 mg/L fluorine exposure groups were (0.48 ± 0.09), (20.01 ± 1.68), (37.45 ± 2.45) mg/L, respectively, with statistically significant differences between the groups ( F = 929.58, P < 0.001). Significant differences in calcium ion levels in urine, kidneys, and serum were observed among the three groups ( F = 14.66, 11.09, 10.31, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group exhibited higher levels of calcium ion in the urine and kidneys, and lower serum calcium ion levels ( P < 0.05). The results of Western blotting analysis revealed that the protein expression levels of TRPV5 and CB-D28K in the kidneys increased with the increase of fluorine exposure level ( Z = 2.11, 2.11, P = 0.035). The protein expression level of NCX1 in the kidneys showed a decreasing trend with increasing fluorine exposure level ( Z = - 2.11, P = 0.035). Significant differences were also observed in the protein expression levels of Klotho and PMCA1b among the three groups ( F = 8.93, 7.08, P < 0.05). Compared with the control group, the 100 mg/L fluorine exposure group showed higher level of Klotho protein expression and lower level of PMCA1b protein expression in the kidneys ( P < 0.05). Immunohistochemical results indicated significant differences in the protein expression levels of TRPV5, CB-D28K, NCX1, and Klotho in the kidneys of the three groups ( F = 27.56, 24.94, 16.05, 32.72, P < 0.05). Compared with the control group, the protein expression levels of TRPV5, CB-D28K, and Klotho in kidneys of 50 and 100 mg/L fluorine exposure groups were higher, while the protein expression levels of NCX1 were lower ( P < 0.05). Conclusion:Fluorine exposure may cause calcium ion metabolism disorders by regulating the expression levels of Klotho and other calcium-regulating proteins in the kidneys.

Objective:To gain a understanding of the occurrence of cognitive impairment among residents in drinking water-borne endemic fluorosis (drinking water-borne fluorosis) areas, and to study its influencing factors.Methods:In March 2023, a cluster sampling method was used to select local residents aged 18 and above from the drinking water-borne fluorosis areas in Jishan County, Shanxi Province as survey subjects. General demographic data were collected through face-to-face surveys, and a random urine sample was collected once to determine urinary fluoride level. Cognitive function was assessed using the mini-mental state examination (MMSE), and the survey subjects were divided into a cognitive impairment group ( < 27 points) and a control group (27 - 30 points) based on the MMSE scores. A multiple logistic regression model and a decision tree model based on chi-squared automatic interaction detector were constructed to analyze the factors affecting cognitive impairment, and the model fitting effect was evaluated using receiver operating characteristic (ROC) curve.Results:A total of 3 301 subjects were included in the survey, including 2 081 females and 1 220 males. There were 1 515 subjects < 60 years old and 1 786 subjects ≥60 years old, with urinary fluoride level [ M ( Q1, Q3)] of 2.92 (1.78, 4.54) mg/L. There were 1 939 cases in the cognitive impairment group and 1 362 cases in the control group, with a detection rate of 58.74% (1 939/3 301) for cognitive impairment; and the differences in gender, age, education level, marital status, annual household income, alcohol consumption, smoking distribution, and urinary fluoride level between the two groups were statistically significant ( P < 0.05). The results of multiple logistic regression analysis showed that female, ≥60 years, and urinary fluoride > 4.54 mg/L were risk factors for cognitive impairment [ OR (95% CI): 1.25 (1.01, 1.54), 2.66 (2.26, 3.14), 1.32 (1.06, 1.65), P < 0.05]. Education level of primary school or above, annual household income≥12 000 yuan, and mild alcohol consumption were protective factors for cognitive impairment [ OR (95% CI): 0.15 (0.09, 0.25), 0.58 (0.48, 0.68), 0.67 (0.51, 0.87), P < 0.05]. The analysis results of the decision tree model showed that age had the greatest impact on the occurrence of cognitive impairment, followed by annual household income, education level, and urinary fluoride. The areas under the ROC curves of the multiple logistic regression and decision tree model were 0.72 and 0.70 ( P < 0.001), respectively, indicating good model fitting performance. Conclusion:The detection rate of cognitive impairment in residents of drinking water-borne fluorosis areas is relatively high, and age, annual household income, education level, and urinary fluoride are all influencing factors for occurrence of cognitive impairment.

Objective:To study the impact of fluoride exposure through drinking water on the risk of hypertension among residents in Jishan County, Shanxi Province.Methods:From March to April 2023, a cluster sampling method was used to select permanent residents aged ≥18 years and residing for ≥10 years in 12 villages in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province as the survey subjects. A questionnaire survey, physical examination, and morning urinary fluoride level testing were conducted. The least absolute shrinkage and selection operator (Lasso) regression were used to analyze the key influencing factors of hypertension. Restricted cubic spline was used to evaluate the linear relationship between urinary fluoride and hypertension. Logistic regression was used to analyze the impact of urinary fluoride on hypertension.Results:Finally, 2 453 survey subjects were included, aged (62 ± 10) years, including 1 565 patients (63.80%) with hypertension. There were significant differences in the distribution of age, gender, education level, annual household income, body mass index (BMI), and the level and distribution of urinary fluoride between hypertension group and normal blood pressure group ( P < 0.05). The Lasso regression results showed that age, education level, BMI, and urinary fluoride were the key influencing factors of hypertension, with coefficients of 1.04, - 0.12, 0.24 and 0.01, respectively. The results of the restricted cubic spline showed that there was a linear relationship between urinary fluoride and hypertension after adjusting for age, education level, and BMI ( Poverall = 0.018, Pnonlinear = 0.482). The logistic regression results showed that after adjusting for age, education level, and BMI, urinary fluoride > 4.68 mg/L was a risk factor for hypertension ( OR = 1.42, 95% CI: 1.10 - 1.84, P = 0.007). Conclusion:High urinary fluoride is a risk factor for hypertension in drinking water-borne endemic fluorosis areas of Jishan County, Shanxi Province.

BACKGROUND:Among the pathogenic factors of cervical spondylosis,herniation of the intervertebral disc,dislocation of the facet joint and the stenosis of the intervertebral foramen are important factors leading to symptoms in patients.Moreover,inappropriate manipulation may aggravate the possibility of cervical disc rupture,leading to exacerbation of symptoms in patients. OBJECTIVE:To compare the effect between sagittal cervical manipulation and traditional cervical rotation manipulation on the area of the intervertebral disc,facet joint and intervertebral foramen at the operative segment by the finite element analysis. METHODS:The neck CT data of a male volunteer with a normal neck were selected and imported into Mimics 17.0 three-dimensional reconstruction software.Geo-magic Studio 12.0,Solidworks 2017 and Ansys Workbench 17.0 software were used for the construction of the finite element model of cervical vertebrae(C3-6)including intervertebral disc and articular cartilage.The lower end plate of the C5 vertebral body was fixed.A uniformly distributed vertical downward 50 N load was applied on the upper surface of the upper vertebral body(C3).The stress,deformation and deformation direction of the C4-5 intervertebral disc,joint capsule stress,the displacement of facet joints and the area of bilateral intervertebral foramen were compared between sagittal cervical manipulation and traditional rotation reduction. RESULTS AND CONCLUSION:(1)When using the rotation technique,the maximum normal equivalent stress(von Mises stress)of the C4-5 disc was 8.06 MPa;the total deformation was 1.05 mm,and the fiber ring expanded to the left and outside.When using the sagittal tip lifting technique,the maximum normal equivalent stress(von Mises stress)of the C4-5 disc was 2.60 MPa;the total deformation was 0.90 mm,and the fiber ring expanded to the left and back.Compared with the rotation technique,the pressure of the cervical manipulation technique on the disc was less(about 32.3%of the rotation technique),and the deformation degree of the disc was also light(about 85.7%of the rotation technique).(2)When the rotation technique was used,the maximum stresses of the left and right articular capsule ligaments were 0.37 MPa and 1.69 MPa,respectively.The overall displacement of the facet joint was 2.21 mm.The area of the right intervertebral foramen decreased by about 3.8%and the area of the left intervertebral foramen increased by about 0.9%.When the sagittal end lifting manipulation was performed,the maximum stresses of the left and right articular capsule ligaments were 0.27 MPa and 1.70 MPa,respectively;the overall displacement of the facet joint was 1.63 mm;the area of the right intervertebral foramen increased by about 2.6%,and the area of the left intervertebral foramen decreased by about 0.9%.Compared with rotation manipulation,sagittal end lifting manipulation had fewer changes in the displacement of facet joint,joint capsule stress and intervertebral foramen area,so it was safer to operate.(3)In conclusion,compared with cervical rotation manipulation,sagittal end lifting manipulation has fewer changes in facet joint displacement,intervertebral disc stress/deformation degree,joint capsule stress,and foraminal area.In clinical practice,more appropriate manipulation should be selected based on biomechanical results after an accurate assessment of patients'conditions.

Objective:To analyze the relationship between dietary composition of residents in endemic fluorosis areas and skeletal fluorosis.Methods:A case-control study was used to analyze the difference of dietary composition between patients with skeletal fluorosis (case group) and residents without skeletal fluorosis (control group). In August 2019, taking the drinking water-borne endemic fluorosis area in Wenshui County, Lvliang City, Shanxi Province as the survey site, a cluster sampling method was adopted to select local residents aged over 18 years old, and a questionnaire survey was conducted by face-to-face interview. The survey contents included gender, age and consumption frequency of various foods. Binary logistic regression was used to analyze the relationship between food consumption frequency and skeletal fluorosis. The diagnosis of skeletal fluorosis was made by using portable digital radiography (DR) to take X-ray films of forearm and lower leg, combining with clinical signs, and according to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008) to determine.Results:A total of 1 061 subjects were included in this study, including 376 in the case group and 685 in the control group. The age composition of patients in the case group (≤60, > 60 years old: 162, 214 cases) was significantly different from that in the control group (≤60, > 60 years old: 423, 261 cases, χ 2 = 34.52, P < 0.001). There was no statistically significant difference in gender ratio (χ 2 = 1.37, P = 0.251). The proportion of patients in the case group who ate meat and eggs > 1 time/week was lower than that in the control group (χ 2 = 8.06, 5.46, P < 0.05), the proportion of patients who ate milk > 1 time/week was higher than that in the control group (χ 2 = 4.01, P = 0.046), and the proportion of patients who ate seafood ≥1 time/week was lower than that in the control group (χ 2 = 4.16, P = 0.046). The results of binary logistic regression analysis showed that after adjusting for age, sex, and urinary fluoride, the frequency of eating meat, eggs or milk > 1 time/week and the frequency of eating seafood ≥1 time/week were not related to the risk of skeletal fluorosis ( P > 0.05); however, in the group ≤60 years old, the frequency of eating eggs > 1 time/week was associated with the risk of skeletal fluorosis [odds ratio ( OR) = 0.59, 95% confidence interval ( CI): 0.39, 0.88]. Conclusions:The consumption frequency of meat, milk, eggs and seafood is significantly different between the skeletal fluorosis patients and the control people. In the population ≤60 years old, consumption frequency of eggs > 1 time/week may reduce the risk of skeletal fluorosis.

Objective:Through determination of urinary arsenic metabolites in high water arsenic exposed areas of Jilin and Shanxi provinces, to explore the mode and possible influencing factors of arsenic metabolism in different populations.Methods:From October 2018 to August 2019, a cluster sampling was carried out in villages (arsenic in drinking water ≥0.05 mg/L) of some townships (towns) in Lyuliang City, Shanxi Province and Baicheng City, Jilin Province for epidemiological investigation and general health examination. The residents over 35 years old drinking water from local centralized water supply and small well water sources were selected as arsenic exposure group, and people (nearby low-arsenic water source areas) with the same diet and living habits and similar economic conditions were selected as control group. Urine samples were collected. Liquid chromatography-atomic fluorescence spectrometry(LC-AFS) technology was used to separate and detect 4 species of arsenic compounds, including trivalent inorganic arsenic (iAs Ⅲ), pentavalent inorganic arsenic (iAs Ⅴ), methylated arsine (MMA), and dimethylated arsine (DMA). Total arsenic (tAs), inorganic arsenic percentage (iAs%), MMA percentage (MMA%), DMA percentage (DMA%), primary methylation index (PMI) and the secondary methylation index (SMI) were calculated. The influencing factors of arsenic metabolism were analyzed by multiple linear regression. Results:A total of 1 415 villagers were investigated, including 1 256 in arsenic exposure group and 159 in control group. Compared with the control group, there were no significant differences in age, gender ratio and occupation distribution between arsenic exposure group and control group ( P > 0.05), but there were significant differences in smoking, drinking, body mass index (BMI) and education level distribution ( P < 0.05). The median of urinary tAs, iAs%, MMA%, DMA%, PMI and SMI in control group and arsenic exposure group were 12.86 μg/L, 15.03, 5.23, 76.35, 84.97, 93.68 and 69.68 μg/L, 10.24, 8.37, 79.31, 89.76, 90.65, respectively, the levels of urinary tAs, DMA% and PMI in arsenic exposed group were higher than those in control group, while iAs% and SMI were lower than those in control group, the differences were statistically significant ( U=- 13.87, - 4.30, - 6.64, - 6.64, - 1.99, P < 0.05). After analysis of the factors influencing urinary arsenic metabolism in the population, we found that age and BMI had an impact on iAs% ( β=- 0.08, - 0.08, P < 0.05); gender, drinking, BMI and education level were influencing factors of MMA% ( β =- 0.11, - 0.09, - 0.07, 0.08, P < 0.05); DMA% was mainly affected by age, gender, BMI and education level ( β = 0.06, 0.09, 0.10, - 0.09, P < 0.05); PMI was mainly affected by age and BMI ( β = 0.08, 0.08, P < 0.05); while SMI was affected by gender, drinking, BMI and education level ( β=0.09, 0.08, 0.08, - 0.09, P < 0.05). Conclusions:The urinary arsenic metabolism models of different arsenic exposed groups are different. Age, gender, smoking, drinking, BMI and education level may be influencing factors of different arsenic metabolism models.

Objective:To investigate the association of single nucleotide polymorphism at the estrogen receptor 1(ESR1) gene rs1801132 with the risk of brick-tea type skeletal fluorosis.Methods:The typical brick-tea type fluorosis areas in Qinghai, Xinjiang, and Inner Mongolia were selected as the survey sites for a cross-sectional study. An epidemiological questionnaire was conducted by the staffs on the sites for participants older than 16 years, and physical examination and X-ray diagnosis were performed. Brick tea, blood, and urine samples were collected at the same time. The diagnosis of skeletal fluorosis through X-ray was based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS/T 192-2008); The determination of tea's fluoride and urinary fluoride was performed by fluoride ion-selective electrode method; gene sequencing analysis of rs1801132 locus of ESR1 gene was done by Sequenom MassARRAY flight mass spectrometry system.Results:A total of 994 patients were included in this study. The total prevalence of skeletal fluorosis was 23.9% (238/994). The prevalence of skeletal fluorosis in Tibetans(39.9%, 123/308) was higher than those of Mongolian and Han nationality [22.2% (58/261), 13.4% (57/425), χ 2=20.435, 67.811, P < 0.05]. Based on binary logistic analysis, the daily tea fluoride intake ≤ 3.5 mg, urinary fluoride content ≤1.6 mg/L, and age ≤45 years were used as the reference groups, and then, when the daily tea fluoride intake > 7.0 mg ( OR=2.865, 95% CI: 1.923-4.268), urinary fluoride content > 1.6-3.2 mg/L ( OR=2.368, 95% CI: 1.686-3.326) and > 3.2 mg/L ( OR=3.559, 95% CI: 2.401-5.276), the age > 45-65 years old ( OR=2.361, 95% CI: 1.603-3.477) and > 65 years old ( OR=4.556, 95% CI: 2.845-7.296), the risk of fluorosis was higher than that of the reference group, respectively. When the daily tea fluoride intake was > 3.5-7.0 mg and the level of urinary fluoride was > 1.6-3.2 mg/L, G allele had a protective effect on skeletal fluorosis in Mongolian population (adjusted OR=0.207, 95% CI: 0.044-0.974); when the daily tea fluoride intake was > 3.5-7.0 mg, gender was male group, G allele had a protective effect on skeletal fluorosis in Han population (adjusted OR=0.315, 95% CI: 0.112-0.887). Conclusion:The single nucleotide polymorphism of the rs1801132 locus at the ESR1 gene may be associated with the risk of susceptibility to brick-tea type skeletal fluorosis in Mongolian and Han nationality.