[Purpose]To analyze the prevalence characteristics and disease burden of lung cancer in Hebei cancer registration areas from 2012 to 2020.[Methods]Lung cancer data were collected from the Hebei Provincial Cancer Registry from 2012 to 2020.The crude incidence/mortality rates,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW)were calculated.The Joinpoint model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC).Years of life lost(YLL)and years lived with disability(YLD)and the disability-adjusted life years(DALY)were calculated.[Results]From 2012 to 2020,the ASIRW of lung cancer in Hebei can-cer registration areas was 33.13/105,44.56/105 for men and 22.54/105 for women,respectively;the incidence rates of urban and rural areas were 29.05/105 and 33.52/105,respectively.The incidence rates increased with ages,reaching a peak in the age group of 80～84 years old.There was a de-creasing trend in the ASIRW of lung cancer(AAPC=-3.99％,P＜0.05).From 2012 to 2020,the ASMRW of lung cancer was 25.80/105,36.56/105 for men and 15.96/105 for women,respectively;the mortality rates of urban and rural areas were 25.14/105 and 26.12/105,respectively.The mor-tality rates increase with ages,reaching a peak in the age group of 85 and above years old.There was a decreasing trend in the mortality of lung cancer(AAPC=-4.65％,P＜0.001)from 2012 to 2020.The DALY of lung cancer in Hebei Province from 2012 to 2020 was 484 194 person-years,with male accounting for 66.77％,female accounted for 33.23％,the DALY rate of lung cancer was 3.31‰,of which 35.57％in urban areas and 64.43％in rural areas.[Conclusion]Lung can-cer incidence and mortality rate in Hebei cancer registration areas from 2012 to 2020 showed a decreasing trend.The disease burden is gradually increasing with age in middle-aged and el-derly population.

[Purpose]To analyze the prevalence characteristics and disease burden of lung cancer in Hebei cancer registration areas from 2012 to 2020.[Methods]Lung cancer data were collected from the Hebei Provincial Cancer Registry from 2012 to 2020.The crude incidence/mortality rates,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW)were calculated.The Joinpoint model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC).Years of life lost(YLL)and years lived with disability(YLD)and the disability-adjusted life years(DALY)were calculated.[Results]From 2012 to 2020,the ASIRW of lung cancer in Hebei can-cer registration areas was 33.13/105,44.56/105 for men and 22.54/105 for women,respectively;the incidence rates of urban and rural areas were 29.05/105 and 33.52/105,respectively.The incidence rates increased with ages,reaching a peak in the age group of 80～84 years old.There was a de-creasing trend in the ASIRW of lung cancer(AAPC=-3.99％,P＜0.05).From 2012 to 2020,the ASMRW of lung cancer was 25.80/105,36.56/105 for men and 15.96/105 for women,respectively;the mortality rates of urban and rural areas were 25.14/105 and 26.12/105,respectively.The mor-tality rates increase with ages,reaching a peak in the age group of 85 and above years old.There was a decreasing trend in the mortality of lung cancer(AAPC=-4.65％,P＜0.001)from 2012 to 2020.The DALY of lung cancer in Hebei Province from 2012 to 2020 was 484 194 person-years,with male accounting for 66.77％,female accounted for 33.23％,the DALY rate of lung cancer was 3.31‰,of which 35.57％in urban areas and 64.43％in rural areas.[Conclusion]Lung can-cer incidence and mortality rate in Hebei cancer registration areas from 2012 to 2020 showed a decreasing trend.The disease burden is gradually increasing with age in middle-aged and el-derly population.

Objective:To investigate the role and significance of heme oxygenase-1 (HO-1) in regulating macrophage polarization on seawater-drowning-induced acute lung injury (ALI) in mice.Methods:Raw 264.7 cells were divided into four groups. The control group was not stimulated with artificial seawater (SW), while the SW 8 h group, SW 24 h group, and SW 72 h group stimulated with artificial seawater for 8 h, 24 h, and 72 h, respectively. The morphological changes of cells were observed, the apoptosis, the contents of inducible nitric oxide synthase (iNOS), and HO-1 protein were detected. Hmox1 flox/ floxCre+ /- and Hmox1 -/- (HO-1 M-KO) mice with conditional knockout of HO-1 gene in alveolar macrophages were produced and randomly divided into HO-1 flox/flox Control group, HO-1 flox/flox SW 24 h group, HO-1 M-KO Control group, and HO-1 M-KO SW 24 h Group, with 6 mice in each group. The mouse model of seawater-drowning-induced ALI was established by placing mice in a hollow container and then immersing them in 6 cm deep and (25±2)℃ artificial seawater for 28 s. Samples were taken 24 hours after seawater drowning to carry out alveolar lavage, and then the total cell counts and protein concentrations in bronchoalveolar lavage fluid (BALF), and the pathological changes and the iNOS protein content in lung tissues were observed. Results:Abnormally shaped Raw 264.7 cells increased while the total number of Raw 264.7 cells decreased after seawater stimulation. The apoptosis rates of the control group, SW 8 h group, SW 24 h group, and SW 72 h group were increased to (5.99±0.23)%, (16.71±1.16)%, (41.80±2.50)%, and (77.84±1.59)%, respectively, with statistically significant differences ( P<0.01). The contents of HO-1 protein in the control group, SW 8 h group, SW 24 h group, and SW 72 h group were (1.07±0.06), (1.42±0.01), (2.77±0.22), and (0.99±0.10), respectively, and the contents of HO-1 protein of both SW 8 h group and SW 24 h group increased significantly ( P<0.05). The contents of iNOS protein in the cells of the control group, SW 8 h group, SW 24 h group, and SW 72 h group were (0.94±0.10), (3.44±0.32), (1.52±0.09), and (2.26±0.11), respectively, and the contents of iNOS protein of SW 8 h group, SW 24 h group, and SW 72 h group increased significantly ( P<0.05); compared with the SW 8 h group, the HO-1 protein content increased significantly, while the iNOS protein content decreased in the SW 24 h group significantly ( P<0.01). Lung tissue injury in HO-1 M-KO mice was significantly aggravated after drowning. The cavity of pulmonary alveoli collapsed and shrunk, intra-alveolar hemorrhage occurred, alveolar septum thickened, and inflammatory cell infiltration aggravated. The cell number and protein concentration in BALF significantly increased ( P<0.01), and the iNOS content in lung tissue significantly increased( P<0.01). Conclusion:HO-1 can alleviate the seawater-drowning-induced ALI in mice by inhibiting the M1 macrophage polarization.

Objective:To investigate the role and significance of heme oxygenase-1 (HO-1) in regulating macrophage polarization on seawater-drowning-induced acute lung injury (ALI) in mice.Methods:Raw 264.7 cells were divided into four groups. The control group was not stimulated with artificial seawater (SW), while the SW 8 h group, SW 24 h group, and SW 72 h group stimulated with artificial seawater for 8 h, 24 h, and 72 h, respectively. The morphological changes of cells were observed, the apoptosis, the contents of inducible nitric oxide synthase (iNOS), and HO-1 protein were detected. Hmox1 flox/ floxCre+ /- and Hmox1 -/- (HO-1 M-KO) mice with conditional knockout of HO-1 gene in alveolar macrophages were produced and randomly divided into HO-1 flox/flox Control group, HO-1 flox/flox SW 24 h group, HO-1 M-KO Control group, and HO-1 M-KO SW 24 h Group, with 6 mice in each group. The mouse model of seawater-drowning-induced ALI was established by placing mice in a hollow container and then immersing them in 6 cm deep and (25±2)℃ artificial seawater for 28 s. Samples were taken 24 hours after seawater drowning to carry out alveolar lavage, and then the total cell counts and protein concentrations in bronchoalveolar lavage fluid (BALF), and the pathological changes and the iNOS protein content in lung tissues were observed. Results:Abnormally shaped Raw 264.7 cells increased while the total number of Raw 264.7 cells decreased after seawater stimulation. The apoptosis rates of the control group, SW 8 h group, SW 24 h group, and SW 72 h group were increased to (5.99±0.23)%, (16.71±1.16)%, (41.80±2.50)%, and (77.84±1.59)%, respectively, with statistically significant differences ( P<0.01). The contents of HO-1 protein in the control group, SW 8 h group, SW 24 h group, and SW 72 h group were (1.07±0.06), (1.42±0.01), (2.77±0.22), and (0.99±0.10), respectively, and the contents of HO-1 protein of both SW 8 h group and SW 24 h group increased significantly ( P<0.05). The contents of iNOS protein in the cells of the control group, SW 8 h group, SW 24 h group, and SW 72 h group were (0.94±0.10), (3.44±0.32), (1.52±0.09), and (2.26±0.11), respectively, and the contents of iNOS protein of SW 8 h group, SW 24 h group, and SW 72 h group increased significantly ( P<0.05); compared with the SW 8 h group, the HO-1 protein content increased significantly, while the iNOS protein content decreased in the SW 24 h group significantly ( P<0.01). Lung tissue injury in HO-1 M-KO mice was significantly aggravated after drowning. The cavity of pulmonary alveoli collapsed and shrunk, intra-alveolar hemorrhage occurred, alveolar septum thickened, and inflammatory cell infiltration aggravated. The cell number and protein concentration in BALF significantly increased ( P<0.01), and the iNOS content in lung tissue significantly increased( P<0.01). Conclusion:HO-1 can alleviate the seawater-drowning-induced ALI in mice by inhibiting the M1 macrophage polarization.

Objective:To investigate the role of NF-E2-related factor 2 (Nrf2) in lung injury caused by seawater drowning in mice.Methods:A total of 48 6-8 weeks old male wild-type C57 mice were randomly divided into two groups for experiment: (1) control group, day 1 group after drowning(Day1), day 3 group after drowning(Day3) and day 7 group after drowning(Day7) to determine the time point of seawater drowning; (2) control group, seawater drowning model group(SW), dimethyl fumarate treatment group(DMF) and seawater drowning+ DMF reatment group(SW+ DMF) to determine the role of Nrf2 in lung injury in mice caused by drowning, 6 mice per group. And 12 male C57 background Nrf2 knockout mice (Nrf2 KO) at 6-8 weeks old were divided into Nrf2 KO control group and Nrf2 KO+ seawater drowning group; 6 mice in each group. Three days after the drowning model was established, we observed the gross morphology and the pathological changes of the lung tissue, calculated the wet-to-dry weight ratio of the lungs, and tested the reduced glutathione and malondialdehyde levels.Results:Seawater drowning caused alveolar space rupture, pulmonary hemorrhage and pulmonary edema in mice. Compared with the wild-type mice, knockout of Nrf2 aggravated lung injury and oxidative stress in mice caused by seawater drowning. Nrf2 agonist DMF treatment significantly improved lung injury in mice, increased the reduced glutathione content, and decreased malondialdehyde level.Conclusion:The activation of Nrf2 can relieve lung injury and oxidative stress levels in mice caused by seawater drowning, which can play an important role in reducing lung damage caused by seawater drowning.

Objective:To investigate the role of NF-E2-related factor 2 (Nrf2) in lung injury caused by seawater drowning in mice.Methods:A total of 48 6-8 weeks old male wild-type C57 mice were randomly divided into two groups for experiment: (1) control group, day 1 group after drowning(Day1), day 3 group after drowning(Day3) and day 7 group after drowning(Day7) to determine the time point of seawater drowning; (2) control group, seawater drowning model group(SW), dimethyl fumarate treatment group(DMF) and seawater drowning+ DMF reatment group(SW+ DMF) to determine the role of Nrf2 in lung injury in mice caused by drowning, 6 mice per group. And 12 male C57 background Nrf2 knockout mice (Nrf2 KO) at 6-8 weeks old were divided into Nrf2 KO control group and Nrf2 KO+ seawater drowning group; 6 mice in each group. Three days after the drowning model was established, we observed the gross morphology and the pathological changes of the lung tissue, calculated the wet-to-dry weight ratio of the lungs, and tested the reduced glutathione and malondialdehyde levels.Results:Seawater drowning caused alveolar space rupture, pulmonary hemorrhage and pulmonary edema in mice. Compared with the wild-type mice, knockout of Nrf2 aggravated lung injury and oxidative stress in mice caused by seawater drowning. Nrf2 agonist DMF treatment significantly improved lung injury in mice, increased the reduced glutathione content, and decreased malondialdehyde level.Conclusion:The activation of Nrf2 can relieve lung injury and oxidative stress levels in mice caused by seawater drowning, which can play an important role in reducing lung damage caused by seawater drowning.

Objective To explore the relationship between iodine and fluoride content in drinking water and the incidence of adult thyroid nodules in Cangzhou,Hebei.Methods According to the previous reports on iodine and fluoride levels in drinking water in Cangzhou,from November 2016 to January 2017,Cangzhou was divided into high iodine,low iodine,normal iodine and fluorine,low iodine and high fluorine,high iodine and high fluorine areas,and according to the different contents of iodine and fluorine in drinking water,high iodine and high fluorine area was further divided into high iodine and high fluorine 1 (iodine:743.30 μg/L,fluorine:4.27 mg/L),2 (iodine:119.31μg/L,fluorine:4.67 mg/L) and 3 (iodine:105.30 μg/L,fluorine:1.64 mg/L) subareas.Subjects who lived for 20 or more years and aged 30 or older,without serious disease and not taken iodized salt were selected.Palpation was used to examine the size,texture,mass,tenderness and mobility of the thyroid gland.The boundary,internal echo,blood flow and quantity of nodules were observed and recorded by color Doppler.Results The prevalence difference of thyroid nodules [36.8％ (629/1 710),32.8％ (636/1 938),25.1％ (427/1 700)] in high iodine,low iodine and normal iodine and fluorine areas was statistically significant (x2 =55.597,P ＜ 0.05).The prevalences of thyroid nodules in both high iodine and low iodine areas were higher than that of normal iodine and fluorine area (P＜ 0.016 7).The prevalence difference of thyroid nodules [43.3％ (749/1 730),39.8％ (712/1 790),34.9％ (623/1 785)] in high iodine and high fluorine 1,2 and 3 subareas was statistically significant(x2 =26.220,P ＜ 0.05).Compared with low iodine area,the prevalence of thyroid nodules [41.2％ (735/1 785)] in low iodine and high fluorine area was increased (x2 =6.288,P ＜ 0.05).Conclusions Both high iodine and low iodine can induce thyroid nodules.In water source areas with high iodine content,both high iodine and high fluorine are the factors inducing thyroid nodules.The prevalence of thyroid nodules in low iodine and high fluorine area is significantly higher than that of low iodine area.

Objective To explore the protective effect of heme oxygenase-1 (HO-1) on lung injury induced by seawater drowning in mice,so as to provide a new strategy for the treatment of lung injury induced by seawater drowning.Methods Forty-eight healthy adult male BALB/c mice were randomly divided into the normal control group (n =8),the zinc protoporphyrin (ZnPP) treatment group(n =8),the seawater drowning group (3-d,7-d and 15-d treatment) (n =24) and the seawater drowning + ZnPP treatment group (n =8).The mice were immersed in the artificial seawater with a water depth of 6 cm and water temperature of (25 ± 2) ℃ for 28 seconds.Then,the moment after the mice were taken out from the water,in-time cardio-pulmonary resuscitation was perfromed and a mouse seawater drowning model was thus established.Gross morphology of the lung tissue was observed,and lung wet/dry weight (W/D) ratio,lactate dehydrogenase (LDH) and superoxide dismutase (SOD) levels were detected accordingly.At the same time,changes in the histopathology of the pulmonary tissue,pulmonary fibrosis,apoptosis and proliferation of lung epithelial cells were also observed.HO-1 protein expression and activity in the lung tissue were measured as well.Results Three and 7 days after seawater drowning,there was pulmonary hemorrhage in the lung tissue.The lung wet/dry ratio and serum LDH level significantly increased,as compared with those of the normal control group (P ＜ 0.05),and the SOD level significantly decreased,as compared with that of the normal control group (P ＜ 0.05).Furthermore,alveolar cavity was damaged,alveolar wall thickened,red blood cells and inflammatory cells were infiltrated.HO-1 protein expression level and activity in the lung tissue significantly increased as compared with those of the normal control group (P ＜ 0.05).The expression levels of HO-1 protein in the normal control group,the 3-d and 7-d seawater drowning groups were respectively (0.313 ± 0.027),(0.604 ± 0.092) and (0.945 ± 0.252),and HO-1 activity in these groups were respectively (75.0 ± 45.6),(220.0 ± 109.5) and (350.0 ± 218.9).Fifteen days after seawater drowning,the above pathological changes in the groups significantly alleviated,and no significant differences could be noted,as compared with those of the normal control group (P ＞0.05).The HO-1 protein expression in the lung tissue was (1.367 ±0.284),which was significantly higher as compared with that of the normal control group (P ＜ 0.05),while HO-1 activity was (125.0 ±50.0),and there were no significant differences,as compared with that of the normal control group (P ＞0.05).Seven days after seawater drowning,the expression of HO-1 protein in the lung tissue for the ZnPP treatment group was (1.192 ± 0.341),which displayed no significant differences from that of the seawater drowning group (1.070 ± 0.119) (P ＞ 0.05),while HO-1 activity was (40.0 ± 22.4),which was significantly lower than that of the seawater drowning group (135.0 ± 51.8) (P ＜ 0.05).As compared with the seawater drowning group,pathological changes in the ZnPP treatment group all obviously worsened 7 days after seawater drowning (P ＞ 0.05),the pulmonary fibrosis and lung epithelial cell apoptosis increased (P ＜ 0.05),and lung epithelial cell proliferation decreased.Conclusion HO-1 could alleviate lung injury induced by seawater drowning through the access of enzyme activity,and it might play an important role in the the course of lung self-repair.

Objective To explore the protective effect of heme oxygenase-1 (HO-1) on lung injury induced by seawater drowning in mice,so as to provide a new strategy for the treatment of lung injury induced by seawater drowning.Methods Forty-eight healthy adult male BALB/c mice were randomly divided into the normal control group (n =8),the zinc protoporphyrin (ZnPP) treatment group(n =8),the seawater drowning group (3-d,7-d and 15-d treatment) (n =24) and the seawater drowning + ZnPP treatment group (n =8).The mice were immersed in the artificial seawater with a water depth of 6 cm and water temperature of (25 ± 2) ℃ for 28 seconds.Then,the moment after the mice were taken out from the water,in-time cardio-pulmonary resuscitation was perfromed and a mouse seawater drowning model was thus established.Gross morphology of the lung tissue was observed,and lung wet/dry weight (W/D) ratio,lactate dehydrogenase (LDH) and superoxide dismutase (SOD) levels were detected accordingly.At the same time,changes in the histopathology of the pulmonary tissue,pulmonary fibrosis,apoptosis and proliferation of lung epithelial cells were also observed.HO-1 protein expression and activity in the lung tissue were measured as well.Results Three and 7 days after seawater drowning,there was pulmonary hemorrhage in the lung tissue.The lung wet/dry ratio and serum LDH level significantly increased,as compared with those of the normal control group (P ＜ 0.05),and the SOD level significantly decreased,as compared with that of the normal control group (P ＜ 0.05).Furthermore,alveolar cavity was damaged,alveolar wall thickened,red blood cells and inflammatory cells were infiltrated.HO-1 protein expression level and activity in the lung tissue significantly increased as compared with those of the normal control group (P ＜ 0.05).The expression levels of HO-1 protein in the normal control group,the 3-d and 7-d seawater drowning groups were respectively (0.313 ± 0.027),(0.604 ± 0.092) and (0.945 ± 0.252),and HO-1 activity in these groups were respectively (75.0 ± 45.6),(220.0 ± 109.5) and (350.0 ± 218.9).Fifteen days after seawater drowning,the above pathological changes in the groups significantly alleviated,and no significant differences could be noted,as compared with those of the normal control group (P ＞0.05).The HO-1 protein expression in the lung tissue was (1.367 ±0.284),which was significantly higher as compared with that of the normal control group (P ＜ 0.05),while HO-1 activity was (125.0 ±50.0),and there were no significant differences,as compared with that of the normal control group (P ＞0.05).Seven days after seawater drowning,the expression of HO-1 protein in the lung tissue for the ZnPP treatment group was (1.192 ± 0.341),which displayed no significant differences from that of the seawater drowning group (1.070 ± 0.119) (P ＞ 0.05),while HO-1 activity was (40.0 ± 22.4),which was significantly lower than that of the seawater drowning group (135.0 ± 51.8) (P ＜ 0.05).As compared with the seawater drowning group,pathological changes in the ZnPP treatment group all obviously worsened 7 days after seawater drowning (P ＞ 0.05),the pulmonary fibrosis and lung epithelial cell apoptosis increased (P ＜ 0.05),and lung epithelial cell proliferation decreased.Conclusion HO-1 could alleviate lung injury induced by seawater drowning through the access of enzyme activity,and it might play an important role in the the course of lung self-repair.

Objective To investigate the effects of aluminum lactate exposure on learning and memory and the transportation of amyloid-beta peptides (Aβ) in cerebrospinal fluid in rats.Methods A total of 80 male Sprague-Dawley rats were randomly divided into solvent control (distilled water) group and low-,medium-,and high-dose aluminum poisoning groups (10,30,and 90 mg/kg aluminum lactate),with 20 rats in each group,and the poisoning procedure was performed by gavage for 2 months.The Morris water maze test was used to test the rats' learning and memory,Western blot was used to measure the expression level of low-density lipoprotein receptor protein-1 (LRP-1) in rats' choroid plexus,and enzyme-linked immunosorbent assay (ELISA) was used to measure the content of Aβ in the cerebrospinal fluid and plasma.Results The Morris water maze test showed that in the place navigation test,with the increasing training time,the escape latency was significantly shortened in each group and showed significant differences between any two groups (P＜0.05).In the spatial probe test,the time spent in target quadrant in the medium-and high-dose groups was 11.52±1.56 s and 10.43 ±5.27 s,respectively,which was significantly shorter than that in the control group and the low-dose group (15.81±3.01 s and 13.91±2.17 s)(P＜0.05).The numbers of platform crossings in the medium-and high-dose groups were 2.64± 1.39 and 1.50±0.76,respectively,which were significantly lower than those in the control group and the low-dose group (4.29±0.914 and 3.56±1.38)(P＜0.05).The results of ELISA showed that the medium-and high-dose groups had significant increases in the content of Aβ1-42 in cerebrospinal fluid (320.35±84.82 pg/ml and 327.68±67.51 pg/ml),which was significantlyhigher than that in the control group(203.46±74.36 pg/ml) (P＜0.05).The content of Aβ1-42 in plasma showed no significant difference between any two groups (P＞0.05),and that of Aβ1-40 in cerebrospinal fluid and plasma also showed no significant difference between any two groups (P＞0.05).The results of Western blot showed that the high-dose group had significantly lower protein expression of LRP-1 than the control group and the low-and medium-dose groups(0.57±0.21 vs 1.00±0.00/0.79±0.15/0.95±0.24,P＜0.05).Conclusion Subchronic aluminum exposure may reduce learning and memory in rats,and the accumulation of Aβ in cerebrospinal fluid may be related to the reduced protein expression of LRP-1 in the choroid plexus,suggesting that aluminum affects learning and memory in rats through reducing the protein expression of LRP-1,influencing the transportation of Aβ,and leading to the accumulation of Aβ.