Epidemiological studies have indicated that a high prevalence rate of lung cancer,bladder cancer and liver cancer in the arsenic exposure population.As a weak mutagenic carcinogen,the mechanism of arsenic induced carcinogenesis has not yet been fully elucidated.In recent years,more and more studies have showed that the DNA methylation and the alternation of histone modification patterns might be involved in the carcinogenesis induced by arsenic.Therefore,in this paper we reviewed the alternation of DNA methylation and histone modification patterns,such as histone acetylation,histone methylation and histone phosphorylation,induced by arsenic exposure;and we also reviewed the role of histone modification and DNA methylation in the process of arsenic carcinogenesis.

Objective To explore characteristics and significance of the indexes of peripheral white blood cell (WBC) in patient with human brucellosis.Methods People checked by brucellosis physical checkup and routine physical checkup at Qiqihar Center for Disease Control and Prevention from December 2014 to December 2015,including 40 acute brucellosis patients (acute group),35 chronic brucellosis patients (chronic group) and 72 healthy people (control group),were selected.Automatic blood analyzer was used to determine the indexes of WBC,lymphocyte count (LY),lymphocyte percentage (LY％),monocytes count (MONO),monocytes percentage (MONO％),eosinophil count (EO),eosinophil percentage (EO％),basophilic granulocyte count (BASO),basophilic granulocyte percentage (BASO％),neutrophils count (NEUT) and neutrophils percentage (NEUT％).The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of WBC parameters in acute and chronic groups.Results Compared to control group,the levels of WBC,EO,EO％,BASO,BASO％,NEUT and NEUT％ were decreased in acute group [(5.222 0-± 2.551 2) × 109/L vs (6.352 5 ± 1.905 8) × 109/L,(0.030 0 ± 0.006 8) × 109/[,vs (0.083 9 ± 0.039 3) × 109/L,(0.54 ± 0.12)％ vs (2.31 ± 0.14)％,(0.009 0 ± 0.001 1) × 109/L vs (0.019 0 ± 0.002 4) × 109/L,(0.17 ± 0.09)％ vs (0.32 ± 0.20)％,(2.698 7 ± 1.948 4) × 109/L vs (4.012 9 ± 1.579 0) × 109/L,(48.13 ± 14.38)％ vs (62.13 ± 9.00)％,all P ＜ 0.05],and the levels of LY,LY％ and MONO％ were increased in acute group [(2.125 3 ± 0.949 9) × 109/L vs (1.794 4 ± 0.606 6) × 109/L,(43.37 ± 14.52)％ vs (29.10 ± 7.97)％,(7.84 ± 2.23)％ vs (6.55 ± 2.04)％,all P ＜ 0.05].Compared to control group,the level of NEUT％ [(54.63 ± 9.26)％] was decreased in chronic group (P ＜ 0.05),and the levels of LY,LY％ and EO [(2.212 0 ± 0.633 2) × 109/L,(36.41 ± 8.51)％,(0.153 9 ± 0.028 8) × 109/L] were increased in chronic group (all P ＜ 0.05).The levels of LY％ and MONO％ [(6.45 ± 1.58)％] in chronic group were lower than those in acute group (all P ＜ 0.05),and the levels of WBC [(6.175 7 ± 1.469 5) × 109/L],EO,EO％ [(2.32 ± 1.21)％],BASO [(0.021 8 ± 0.001 9) × 109/L],BASO％ [(0.37 ± 0.21)％] and NEUT％ were higher than those in acute group (all P ＜ 0.05).The areas under ROC curve (AUCs) of LY and MONO in acute group were 0.681 and 0.529,they were in 0.5-0.7,and the diagnostic value was low;the AUCs of EO,EO％,LY％,NEUT％,NEUT,BASO,BASO％,MONO％ and WBC in acute group were 0.816,0.816,0.806,0.790,0.766,0.760, 0.721,0.715 and 0.710,they were in ＞ 0.7-0.9,and the diagnostic value was medium.The AUCs of LY,NEUT,BASO,EO,BASO％,EO％,MONO％,MONO and WBC in chronic group were 0.693,0.617,0.586,0.584,0.581,0.541,0.500,0.513 and 0.510,they were in 0.5-0.7,and the diagnostic value was low;the AUCs of LY％ and NEUT％ in chronic group were 0.725 and 0.717,they were in ＞ 0.7-0.9,and the diagnostic value was medium.Conclusion The indexes of peripheral WBC in patient with acute and chronic human brucellosis are changed abnormally,which has a certain reference value in diagnosis of human brucellosis.

Objective To explore the effects of different doses of sodium fluoride (NaF) on cartilage lesion and expression of interleukin-6 (IL-6) in serum and cartilage tissue of Balb/c mice.Methods Sixty-four 5-week-old male Balb/c mice were divided into 4 groups based on body weight via the random number table method and 16 mice were in each group.The mice in control group were fed with distilled water,and experimental animals in low,middle and high fluoride groups were fed with distilled water containing NaF 25,50 and 100 mg/L,respectively.The mice were weighed once a week and fed for three months to establish the drinking water fluorosis model.The fluoride contents in spine were detected via the fluorin-ion selective electrode method.The pathological changes in articular cartilage and epiphyseal plate cartilage were observed through optical microscope.The levels of serum IL-6 and souble IL-6 receptor (sIL-6R) were detected via the enzyme-linked immunosorbent assay.The expression of IL-6 protein in articular cartilage and epiphyseal plate cartilage was examined by immunohistochemistry.Results From the sixth week of the experiment,compared with other 3 groups,the body weight of high fluoride group decreased significantly (all P ＜ 0.05);from the seventh week,compared with control and low fluoride groups,the body weight of middle fluoride group decreased significantly (all P ＜ 0.05);throughout the experiment,compared with control group,the body weight of low fluoride group had not changed significantly (all P ＞ 0.05).The fluoride contents of bone in control group,low fluoride group,middle fluoride group and high fluoride group were (842.46 ± 89.27),(1 705.05 ± 105.76),(2 614.17 ± 156.10) and (3 444.58 ± 233.69) mg/kg,respectively.The differences between groups were statistically significant (F =309.716,P ＜ 0.05),and fluoride contents of bone increased with increase of fluoride doses (all P ＜ 0.05).Under optical microscope,the cartilage tissue of control group was normal,while articular cartilage and epiphyseal plate cartilage showed different degrees of cartilage ossification in fluorosis mice and the changes increased with the increase of fluoride doses.The levels of serum IL-6 in control group,low fluoride group,middle fluoride group and high fluoride group were (5.98 ± 1.43),(7.54 ± 2.16),(5.25 ± 1.97) and (6.31 ±-1.36) ng/L,respectively.The differences between groups were statistically significant (F =3.840,P ＜ 0.05),low fluoride group was significantly higher than control group (P ＜ 0.05),and middle fluoride group was significantly lower than low fluoride group (P ＜ 0.05).The levels of serum slL-6R in control group,low fluoride group,middle fluoride group and high fluoride group were (0.83 ± 0.20),(0.93 ± 0.23),(0.82 ±0.27) and (0.92 ± 0.28) μg/L,respectively.The differences between groups were not statistically significant (F =0.738,P ＞ 0.05).Immunohistochemical results showed that articular cartilage full-layer cells in each group expressed IL-6 protein especially in the middle layer of chondrocytes,while IL-6 protein only expressed in hypertrophic chondrocytes of epiphyseal plate cartilage.Comparing with other groups,IL-6 positive cells were the most and had the deepest staining in low fluoride group.Conclusions Different doses of NaF could not only cause cartilage lesion,but also change the expression of IL-6 in serum and cartilage tissue of Balb/c mice.The results indicate that IL-6 may be involved in the cartilage lesion caused by fluoride.

Objective To detect the modification levels of H2AKll9 ubiquitination (H2AK119ub) and H2BK120ub,and to analyze the relationship between the levels of H2AK119ub,H2BK120ub and arsenic exposure.Methods A cross-sectional study was conducted in typical areas of drinking water type of endemic arsenicosis in Shanxi and Jilin provinces.Totally 281 residents who had drank local water for more 10 years were enrolled in this study,these participants were divided into control group (water arsenic content ＜ 0.01 mg/L),low arsenic exposure group (water arsenic content ranged 0.01-0.05 mg/L),medium arsenic exposure group (water arsenic content ranged ＞ 0.05-0.10 mg/L) and high arsenic exposure group (water arsenic content ＞ 0.10 mg/L).Among them,including 60 subjects in control group (20 males and 40 females),61 subjects in low arsenic exposure group (27 males and 34 females),50 subjects in medium arsenic exposure group (17 males and 33 females),and 110 subjects in high arsenic exposure group (40 males and 70 females).Drinking water and urine samples were collected and the arsenic content was detected by the method of atomic fluorescence spectrometry.After extracting leukocytes histone from the peripheral venous blood that collected from the subjects,the levels of H2AK119ub and H2BK120ub were detected by dot blotting.The levels of water arsenic,urinary arsenic,water arsenic accumulative intake,H2AK119ub and H2BK120ub were expressed as medium and quartile [M (P25,P75)].Results Age,body mass index (BMI),gender,smoking and alcohol drinking between control group and water arsenic exposure groups had no statistical differences (x2 =3.780,3.572,1.938,4.937,6.025,all P ＞ 0.05).Compared the contents of water arsenic [0.005 (0.003,0.006),0.024 (0.017,0.037),0.076 (0.057,0.084),0.150 (0.124,0.185) mg/L],the contents of urinary arsenic [0.011 (0.006,0.017),0.018 (0.004,0.072),0.061 (0.032,0.124),0.134 (0.069,0.223) mg/L],the water arsenic accumulative intake [0.342 (0.248,0.477),1.641 (1.012,2.324),5.273 (3.690,7.036),7.716 (5.608,12.053) mg] among the control,low,medium and high arsenic exposure groups,the differences were statistically significant (Hc =256.041,88.615,218.610,all P ＜ 0.01).Compared the levels of H2AK119ub [1.231 (0.856,1.817),1.244 (0.792,1.884),1.376 (0.743,1.981),1.390 (0.906,2.045)],H2BK120ub [0.350 (0.186,0.589),0.363 (0.152,0.678),0.428 (0.134,0.788),0.276 (0.146,0.453)] in human peripheral blood leukocytes among control,low,medium and high arsenic exposuregroups,the differences were not statistically significant (Hc =2.130,4.330,all P ＞ 0.05).There were no correlations between H2AK119ub and water arsenic content,water arsenic accumulative intake (r =0.104,-0.008,all P ＞ 0.05);there was a positive correlation between H2AK119ub and urinary arsenic content (r =0.166,P ＜ 0.05).There were negative correlations between H2BK120ub and water arsenic content,water arsenic accumulative intake (r =-0.183,-0.159,all P ＜ 0.05);there was no correlation between H2BK120ub and urinary arsenic content (r =-0.101,P ＞ 0.05).There was a negative correlation between H2AK119ub and H2BK120ub (r =-0.127,P ＜ 0.05).Conclusion External exposure to arsenic may change the levels of H2BK120ub in human peripheral blood leukocytes.

Objective To investigate the relationship between Cytochrome P-450 1A1 (CYP1A1) gene polymorphism and the ethnic differences to brick-tea fluorosis and the gene-environment interaction.Methods Inhabitants over the age of 16 years old in Inner Mongolia,Qinghai and Xinjiang were investigated.The questionnaire survey included basic information,dietary survey and total fluoride intake,and peripheral venous blood was collected.The CYP1A1 gene single nucleotide polymorphism (SNP) genotyping was determined using mass spectrometry;the diagnosis of skeletal fluorosis was based on the X-ray method;combined genetic factors with environmental factors,the interaction of gene-environment was analyzed.Results In the 1 414 copies of whole blood samples (308 Tibetans,290 Kazakhs,261 Mongolians,425 Han people,130 Russians),CYP1A1 genes rs1048943 sites were typed into AA,AG and GG genotypes,and gene distribution met Hardy-Weinberg equilibrium (P ＞ 0.05).The frequencies of genotypes AA,AG and GG in Tibetans were 55.8％ (172/308),37.3％ (115/308) and 6.8％ (21/308),respectively;the frequencies of the three genotypes in Kazakhs were 69.7％ (202/290),27.6％ (80/290) and 2.8％ (8/290),respectively;the frequencies of the three genotypes in Mongolians were 60.5％ (158/261),36.0％ (94/261) and 3.4％ (9/261),respectively;the frequencies of the three genotypes in Han people were 60.9％ (259/425),33.6％ (143/ 425) and 5.4％ (23/425),respectively;the frequencies of genotypes in Russians were 72.3％ (94/130),26.9％ (35/130) and 0.8％ (1/130),respectively;the differences of the three genotype frequencies between different ethnic groups were statistically significant (x2 =24.757,P ＜ 0.05).The skeletal fluorosis detection rates in different ethnic from high to low were Tibetans (39.94％,123/308),Kazakhs (33.79％,98/290),Mongolians (22.22％,58/261),Han people (13.41％,57/425) and Russians (8.46％,11/130),and the differences were statistically significant (x2 =100.156,P＜ 0.05).Skeletal fluorosis detection rates of different genotypes were AA (24.18％,214/885),AG/GG (25.14％,133/529),the difference was not statistically significant between the groups (x2 =0.165,P ＞ 0.05).After the ethnic stratification,the differences were also not statistically significant (P ＞ 0.05).Only in the group of Tibetans whose urine fluoride level was 1.6-3.2 mg/L and Mongolians under age 45 were found that the G gene was one of the risk factors in skeletal fluorosis [OR =2.035,95％ CI (1.003-4.128);OR =5.602,95％CI (1.461-21.479)];G gene might be a protective factor in the Mongolians aged 45 years and over [OR =0.422,95％CI(0.190-0.938)].Conclusion This study does not find a positive correlation between CYP1A1 gene polymorphism and the ethnic differences to bricktea fluorosis.