1.Effects of Huanshaodan on learning and memory impairment and p38MAPK/ERK1/2 signaling pathway in Alzheimer's disease model mice
Zhengda YIN ; Peiwei CONG ; Danyu ZHAO ; Lu REN ; Xu WANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(2):104-110
Objective:To investigate the effect of Huanshaodan on improving learning and memory impairment in a mouse model of Alzheimer's disease (AD) which was named with senescence accelerated mouse-prone 8(SAMP8), as well as the neuroinflammatory response mechanisms mediated by the p38 mitogen activated protein kinase (p38MAPK) and extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling pathways.Methods:Seven-month-old SPF grade male SAMP8 mice were randomly assigned into three groups(6 mice in each group) using a random number table: model group, low-dose Huanshaodan group(1.17g/kg, twice daily via gavage), and high-dose Huanshaodan group(2.34g/kg, twice daily via gavage).Weight-matched seven-month-old male mice with anti-rapid aging traits(senescence-accelerated mouse-resistant 1, SAMR1)were designated as the normal control group( n=6).The mice in control group and the model group received 0.9% NaCl via gavage twice daily.All mice underwent continuous interventions for 28 days.The learning and memory abilities were assessed by Morris water maze.Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP) and ionized calcium-binding adaptor molecule-1(Iba1) as markers for astrocytes and microglial cells in the hippocampus, respectively.ELISA was used to measure pro-inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in hippocampal tissue.Western blot was used for analyzing the expression levels of pro-inflammatory enzymes, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2), as well as phosphorylated levels of ERK1/2 and p38MAPK in hippocampal tissue.Data were statistically analyzed using SPSS 20.0.The repeated measures analysis of variance or one-way analysis of variance was used for multi groups comparison. Results:Morris water maze test results indicated interactions between time and group in the escape latencies of the four groups of mice( F=3.787, P<0.05).From the 5th to 6th day, the escape latencies of the low- and high-dose Huanshaodan groups were lower than those of the model group(both P<0.05).On the 4th to 6th day, the escape latencies of the high-dose Huanshaodan group were lower than those of the low-dose group(all P<0.05).Significant differences were observed in the residence time in the target quadrant and the number of crossing the platform among the four groups of mice( F=8.587, 12.633, both P<0.05).The residence time in the target quadrant of the model group((17.8±3.4)s) and the number of crossing the platform((1.6±0.6)times)were less than those of the control group((40.6±3.7)s, (4.6±0.6)times) and high-dose Huanshaodan group(31.8±4.0)s, (2.8±0.8)times), all P<0.05).Western blot results indicated significant differences in the expression of iNOS, COX-2, p-p38MAPK/p38MAPK, and p-ERK1/2/ERK1/2 in the hippocampal tissues of the four groups of mice( F=207.516, 10.627, 108.497, 34.330, all P<0.05) and the indexes in model group were all higher than those of control group and high-dose Huanshaodan group(all P<0.05).ELISA results revealed significant differences in the levels of IL-6, TNF-α and IL-1β in the serum of the four groups of mice( F=66.790, 82.424, 42.919, all P<0.05), and the indexes of model group were higher than those of the other three groups(all P<0.05).Immunofluorescence results showed significant differences in the relative fluorescence intensity of GFAP and Iba1 in the hippocampal tissues of the four groups of mice( F=20.269, 56.437, both P<0.05).The relative fluorescence intensity values of GFAP and Iba1 in the hippocampal tissues of the high-dose Huanshaodan group were lower than those of the model group(both P<0.05), while the expression level of Iba1 in high-dose group was lower than that in the low-dose group( P<0.05). Conclusion:High-dose Haunshaodan may inhibit the activation of hippocampal glial cells by blocking the p38MAPK and ERK1/2 pathways, reducing neuroinflammation, then improving learning and memory disorders in SAMP8 mice.
2.The relationship between multiple elements in urine and arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region
Yuchen GUO ; Binggan WEI ; Fan ZHAO ; Xinye LI ; Rui WANG ; Shuhui YIN ; Nan WU ; Lingling HE ; Zhen DI ; Kaiwen LIU ; Wei SONG ; Hui WANG ; Zhongbing ZHANG ; Danyu DENG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(7):535-542
Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.
3.Analysis of influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region in 2024
Fan ZHAO ; Zhong YANG ; Kaifeng XU ; Fenxia LI ; Shifang ZHANG ; Xinye LI ; Cong LIU ; Mengxin LI ; Yuchen GUO ; Tianrui ZHUANG ; Ke LI ; Zhixian YANG ; Danyu DENG ; Zhongbing ZHANG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(3):232-236
Objective:To investigate the influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.Methods:A case-control study was conducted in January 2024 to select adult fluorosis patients (case group) and healthy individuals (control group) from the drinking water-borne endemic fluorosis areas in Helinger County, Hohhot City, Inner Mongolia Autonomous Region as the survey subjects. Urine samples were collected to determine urinary fluoride concentration. A questionnaire survey was conducted. SPSS 25.0 software was used for χ 2 test and multivariate logistic regression analysis. Restricted cubic spline (RCS) was used to analyze the association between urinary fluoride concentration and the risk of dental fluorosis in adults. Results:A total of 161 individuals were included in the survey, including 100 in the case group and 61 in the control group. The results of univariate analysis showed that there were statistically significant differences in the distribution of gender, smoking, and urinary fluoride concentration between the case group and the control group (χ 2 = 7.54, 5.02, 9.69, P < 0.05). The results of multivariate logistic regression analysis indicated that gender ( OR = 0.36, 95% CI: 0.18 - 0.73, P = 0.005) and urinary fluoride concentration ( OR = 3.08, 95% CI: 1.46 - 6.67, P = 0.003) were the influencing factors of adult fluorosis. RCS analysis showed a significant linear dose-response relationship between the risk of dental fluorosis and urinary fluoride concentration ( Poverall trend = 0.001, Pnonlinear = 0.071). When the urinary fluoride concentration was greater than 1.57 mg/L, the risk of dental fluorosis increased with the increase of urinary fluoride concentration. Conclusion:Gender and urinary fluoride concentration are the risk factors of dental fluorosis in adults in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.
4.Effects of Huanshaodan on learning and memory impairment and p38MAPK/ERK1/2 signaling pathway in Alzheimer's disease model mice
Zhengda YIN ; Peiwei CONG ; Danyu ZHAO ; Lu REN ; Xu WANG
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(2):104-110
Objective:To investigate the effect of Huanshaodan on improving learning and memory impairment in a mouse model of Alzheimer's disease (AD) which was named with senescence accelerated mouse-prone 8(SAMP8), as well as the neuroinflammatory response mechanisms mediated by the p38 mitogen activated protein kinase (p38MAPK) and extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling pathways.Methods:Seven-month-old SPF grade male SAMP8 mice were randomly assigned into three groups(6 mice in each group) using a random number table: model group, low-dose Huanshaodan group(1.17g/kg, twice daily via gavage), and high-dose Huanshaodan group(2.34g/kg, twice daily via gavage).Weight-matched seven-month-old male mice with anti-rapid aging traits(senescence-accelerated mouse-resistant 1, SAMR1)were designated as the normal control group( n=6).The mice in control group and the model group received 0.9% NaCl via gavage twice daily.All mice underwent continuous interventions for 28 days.The learning and memory abilities were assessed by Morris water maze.Immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP) and ionized calcium-binding adaptor molecule-1(Iba1) as markers for astrocytes and microglial cells in the hippocampus, respectively.ELISA was used to measure pro-inflammatory cytokines interleukin-6(IL-6), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in hippocampal tissue.Western blot was used for analyzing the expression levels of pro-inflammatory enzymes, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2), as well as phosphorylated levels of ERK1/2 and p38MAPK in hippocampal tissue.Data were statistically analyzed using SPSS 20.0.The repeated measures analysis of variance or one-way analysis of variance was used for multi groups comparison. Results:Morris water maze test results indicated interactions between time and group in the escape latencies of the four groups of mice( F=3.787, P<0.05).From the 5th to 6th day, the escape latencies of the low- and high-dose Huanshaodan groups were lower than those of the model group(both P<0.05).On the 4th to 6th day, the escape latencies of the high-dose Huanshaodan group were lower than those of the low-dose group(all P<0.05).Significant differences were observed in the residence time in the target quadrant and the number of crossing the platform among the four groups of mice( F=8.587, 12.633, both P<0.05).The residence time in the target quadrant of the model group((17.8±3.4)s) and the number of crossing the platform((1.6±0.6)times)were less than those of the control group((40.6±3.7)s, (4.6±0.6)times) and high-dose Huanshaodan group(31.8±4.0)s, (2.8±0.8)times), all P<0.05).Western blot results indicated significant differences in the expression of iNOS, COX-2, p-p38MAPK/p38MAPK, and p-ERK1/2/ERK1/2 in the hippocampal tissues of the four groups of mice( F=207.516, 10.627, 108.497, 34.330, all P<0.05) and the indexes in model group were all higher than those of control group and high-dose Huanshaodan group(all P<0.05).ELISA results revealed significant differences in the levels of IL-6, TNF-α and IL-1β in the serum of the four groups of mice( F=66.790, 82.424, 42.919, all P<0.05), and the indexes of model group were higher than those of the other three groups(all P<0.05).Immunofluorescence results showed significant differences in the relative fluorescence intensity of GFAP and Iba1 in the hippocampal tissues of the four groups of mice( F=20.269, 56.437, both P<0.05).The relative fluorescence intensity values of GFAP and Iba1 in the hippocampal tissues of the high-dose Huanshaodan group were lower than those of the model group(both P<0.05), while the expression level of Iba1 in high-dose group was lower than that in the low-dose group( P<0.05). Conclusion:High-dose Haunshaodan may inhibit the activation of hippocampal glial cells by blocking the p38MAPK and ERK1/2 pathways, reducing neuroinflammation, then improving learning and memory disorders in SAMP8 mice.
5.Liuwei Dihuangwan lnterferes with the Molecular Mechanism of Autophagy Prevention and Treatment of Alzheimer's Disease through FcγRⅡB/c-Src Pathway
Wenxiao HOU ; Ruihao SI ; Yuxi LIU ; Zhongkang ZHU ; Zhengda YIN ; Xu WANG ; Danyu ZHAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(3):724-738
Objective To study the effect of Liuwei Dihuangwan on autophagy level and its mechanism in SAMP8 mice and Aβ-stimulated BV2 cell model,and to explore the molecular mechanism of tonifying the kidney and filling up the essence to prevent and control Alzheimer's disease(AD)through interfering with autophagy.Methods Ten 7-month-old male anti-aging mice(SAMR1)were taken as the normal group,and 40 7-month-old male rapid aging mice(SAMP8)were randomly control and model groups,equal volumes of saline were administered by gavage twice a day for 4 weeks,and the levels of Aβ expression in the hippocampus of the mice in each group were detected by immunofluorescence;The expression levels of FcγRⅡB,c-Src and SHP-1 in the hippocampus of each group were detected by Western blot;BV2 cells were cultured and Fcγ receptor Ⅱ-b(FcγRⅡB)overexpression vectors were constructed;the AD state cell model was established by treating the BV2 cells with 5 μmol·L-1 Aβ1-42,and the Liuwei Dihuangwan drug-containing serum was prepared.The cells were divided into NC group,Aβ1-42 group,blank serum group,drug-containing serum group,Vector group,FcγRⅡB OE group,and drug-containing serum+FcγRⅡB OE group;immunofluorescence was used to detect the expression level of Aβ protein in the cells of each group;Western blot was used to detect the expression level of p62,LC3 Ⅱ/Ⅰ,FcγRⅡB,SHP-1,and c-Src in cells of each group.Results Compared with the normal group,the hippocampal Aβ,FcγRⅡB,SHP-1,and c-Src expression levels in the model group of mice were significantly higher(P<0.01),and compared with the model group,the expression levels of Aβ,FcγRⅡB,SHP-1,and c-Src in the low-,medium-,and high-dose groups of Liuwei Dihuangwan were significantly lower(P<0.01),it also showed a significant dose dependent relationship.Compared with NC group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in Aβ1-42 group were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with Aβ1-42 group and blank serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in drug-containing serum group were significantly decreased(P<0.01),and LC3Ⅱ/Ⅰ was significantly increased(P<0.01);Compared with NC group and Vector group,the expression of Aβ in FcγRⅡB OE group was increased,the protein expressions of p62,FcγRⅡB,SHP-1 and c-Src were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with the drug-containing serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in the drug-containing serum+FcγRⅡB OE group were significantly increased(P<0.01),and the protein expression levels of LC3Ⅱ/Ⅰ were significantly decreased(P<0.01).Conclusion Liuwei Dihuangwan improved AD by inhibiting microglia FcγRⅡB/c-Src pathway and increasing autophagy level.
6.Analysis of influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region in 2024
Fan ZHAO ; Zhong YANG ; Kaifeng XU ; Fenxia LI ; Shifang ZHANG ; Xinye LI ; Cong LIU ; Mengxin LI ; Yuchen GUO ; Tianrui ZHUANG ; Ke LI ; Zhixian YANG ; Danyu DENG ; Zhongbing ZHANG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(3):232-236
Objective:To investigate the influencing factors of adult dental fluorosis in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.Methods:A case-control study was conducted in January 2024 to select adult fluorosis patients (case group) and healthy individuals (control group) from the drinking water-borne endemic fluorosis areas in Helinger County, Hohhot City, Inner Mongolia Autonomous Region as the survey subjects. Urine samples were collected to determine urinary fluoride concentration. A questionnaire survey was conducted. SPSS 25.0 software was used for χ 2 test and multivariate logistic regression analysis. Restricted cubic spline (RCS) was used to analyze the association between urinary fluoride concentration and the risk of dental fluorosis in adults. Results:A total of 161 individuals were included in the survey, including 100 in the case group and 61 in the control group. The results of univariate analysis showed that there were statistically significant differences in the distribution of gender, smoking, and urinary fluoride concentration between the case group and the control group (χ 2 = 7.54, 5.02, 9.69, P < 0.05). The results of multivariate logistic regression analysis indicated that gender ( OR = 0.36, 95% CI: 0.18 - 0.73, P = 0.005) and urinary fluoride concentration ( OR = 3.08, 95% CI: 1.46 - 6.67, P = 0.003) were the influencing factors of adult fluorosis. RCS analysis showed a significant linear dose-response relationship between the risk of dental fluorosis and urinary fluoride concentration ( Poverall trend = 0.001, Pnonlinear = 0.071). When the urinary fluoride concentration was greater than 1.57 mg/L, the risk of dental fluorosis increased with the increase of urinary fluoride concentration. Conclusion:Gender and urinary fluoride concentration are the risk factors of dental fluorosis in adults in drinking water-borne endemic fluorosis areas of Inner Mongolia Autonomous Region.
7.Liuwei Dihuangwan lnterferes with the Molecular Mechanism of Autophagy Prevention and Treatment of Alzheimer's Disease through FcγRⅡB/c-Src Pathway
Wenxiao HOU ; Ruihao SI ; Yuxi LIU ; Zhongkang ZHU ; Zhengda YIN ; Xu WANG ; Danyu ZHAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(3):724-738
Objective To study the effect of Liuwei Dihuangwan on autophagy level and its mechanism in SAMP8 mice and Aβ-stimulated BV2 cell model,and to explore the molecular mechanism of tonifying the kidney and filling up the essence to prevent and control Alzheimer's disease(AD)through interfering with autophagy.Methods Ten 7-month-old male anti-aging mice(SAMR1)were taken as the normal group,and 40 7-month-old male rapid aging mice(SAMP8)were randomly control and model groups,equal volumes of saline were administered by gavage twice a day for 4 weeks,and the levels of Aβ expression in the hippocampus of the mice in each group were detected by immunofluorescence;The expression levels of FcγRⅡB,c-Src and SHP-1 in the hippocampus of each group were detected by Western blot;BV2 cells were cultured and Fcγ receptor Ⅱ-b(FcγRⅡB)overexpression vectors were constructed;the AD state cell model was established by treating the BV2 cells with 5 μmol·L-1 Aβ1-42,and the Liuwei Dihuangwan drug-containing serum was prepared.The cells were divided into NC group,Aβ1-42 group,blank serum group,drug-containing serum group,Vector group,FcγRⅡB OE group,and drug-containing serum+FcγRⅡB OE group;immunofluorescence was used to detect the expression level of Aβ protein in the cells of each group;Western blot was used to detect the expression level of p62,LC3 Ⅱ/Ⅰ,FcγRⅡB,SHP-1,and c-Src in cells of each group.Results Compared with the normal group,the hippocampal Aβ,FcγRⅡB,SHP-1,and c-Src expression levels in the model group of mice were significantly higher(P<0.01),and compared with the model group,the expression levels of Aβ,FcγRⅡB,SHP-1,and c-Src in the low-,medium-,and high-dose groups of Liuwei Dihuangwan were significantly lower(P<0.01),it also showed a significant dose dependent relationship.Compared with NC group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in Aβ1-42 group were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with Aβ1-42 group and blank serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in drug-containing serum group were significantly decreased(P<0.01),and LC3Ⅱ/Ⅰ was significantly increased(P<0.01);Compared with NC group and Vector group,the expression of Aβ in FcγRⅡB OE group was increased,the protein expressions of p62,FcγRⅡB,SHP-1 and c-Src were significantly increased(P<0.01),and LC3Ⅱ/Ⅰ was significantly decreased(P<0.01);Compared with the drug-containing serum group,the protein expressions of Aβ,p62,FcγRⅡB,SHP-1 and c-Src in the drug-containing serum+FcγRⅡB OE group were significantly increased(P<0.01),and the protein expression levels of LC3Ⅱ/Ⅰ were significantly decreased(P<0.01).Conclusion Liuwei Dihuangwan improved AD by inhibiting microglia FcγRⅡB/c-Src pathway and increasing autophagy level.
8.The relationship between multiple elements in urine and arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region
Yuchen GUO ; Binggan WEI ; Fan ZHAO ; Xinye LI ; Rui WANG ; Shuhui YIN ; Nan WU ; Lingling HE ; Zhen DI ; Kaiwen LIU ; Wei SONG ; Hui WANG ; Zhongbing ZHANG ; Danyu DENG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(7):535-542
Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.
9.Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study
Xiaoshuai ZHANG ; Bingcheng LIU ; Xin DU ; Yanli ZHANG ; Na XU ; Xiaoli LIU ; Weiming LI ; Hai LIN ; Rong LIANG ; Chunyan CHEN ; Jian HUANG ; Yunfan YANG ; Huanling ZHU ; Ling PAN ; Xiaodong WANG ; Guohui LI ; Zhuogang LIU ; Yanqing ZHANG ; Zhenfang LIU ; Jianda HU ; Chunshui LIU ; Fei LI ; Wei YANG ; Li MENG ; Yanqiu HAN ; Li'e LIN ; Zhenyu ZHAO ; Chuanqing TU ; Caifeng ZHENG ; Yanliang BAI ; Zeping ZHOU ; Suning CHEN ; Huiying QIU ; Lijie YANG ; Xiuli SUN ; Hui SUN ; Li ZHOU ; Zelin LIU ; Danyu WANG ; Jianxin GUO ; Liping PANG ; Qingshu ZENG ; Xiaohui SUO ; Weihua ZHANG ; Yuanjun ZHENG ; Qian JIANG
Chinese Journal of Hematology 2024;45(3):215-224
Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.
10.Relationship between skin injury outcome and urinary arsenic methylation metabolites levels in people exposed to arsenic through drinking water
Xinye LI ; Danyu DENG ; Fan ZHAO ; Cong LIU ; Mengxin LI ; Zhen DI ; Na CUI ; Yijun LIU ; Chang KONG ; Binggan WEI ; Yanhong LI ; Yajuan XIA ; Zhiwei GUO
Chinese Journal of Endemiology 2024;43(6):446-451
Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.

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