Arsenic is a carcinogenic metal-like poison that is widely present in the natural environment. Acute or long-term exposure to arsenic can cause a series of liver injury, such as hepatomegaly, liver fibrosis, cirrhosis, and even liver cancer. In recent years, new progress has been made in the study of the mechanism of arsenic exposure on liver injury. This article will systematically review the main pathogenesis of arsenic-induced liver injury, mainly covering DNA methylation, oxidative stress, inflammatory response, hepatocyte apoptosis, liver fibrosis and autophagy. It aims to provide a theoretical reference for the prevention and treatment of arsenic poisoning.

Objective To observe the effects of Eldepryl on expressions of tyrosine hydroxylase (TH) and glial cell line-derived neurotrophic factor (GDNF) in substantia nigra and striatum in Parkinson’s disease (PD) and to explore the protective mechanism of Eldepryl on dopaminergic neuron . Methods Healthy male Sprague-Dawley (SD) rats (n=72) were randomly divided into control group, model group and Eldepryl group (n=24 in each group). Each group was divided random?ly into 2 subgroups as 4 day treatment group and 8 day treatment group (n=12 in each subgrop). Pakinson’s disease model was established by injecting rotenone subcutaneously back the neck, rats in the control group were injected with an equal vol?ume of sunflower oil subcutaneously at the same location. Rats in the Eldepryl group were then given Eldepryl 0.5 mg·kg-1 in?tragastrically every day for 4 or 8 consecutive days and rats in model group and control group were given an equal volume of saline instead. The expression of TH and GDNF in substantia nigra and striatum were detected by immunohistochemistry and Western blotting. Results Immunohistochemistry and Western blotting showed that strong expression of TH positive cells with little expression of GDNF positive cells were seen in substantia nigra and striatum in rats of control group, and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within control group. The expression of TH cells and GDNF were both significantly reduced in model group compared with those in control group (both P<0.05), and there was no significant difference between subgroup of 8 day treatment and 4 day treatment within each group. The ex?pression of TH positive cells were significantly reduced in Eldepryl group compared with those in control group, and were sig?nificantly increased compared with those in model group. The expression of GDNF positive cells were significantly increased in Eldepryl group compared with those in control group and model group (all P<0.05). And there were significantly more ex?pression of TH positive cells and GDNF positive cells at subgroup of 8 day treatment compared with those at subgroup of 4 day treatment within Eldepryl group with (all P<0.05). Conclusion These data suggest that Eldepryl can protect the dam?age of dopaminergic neurons in substantia nigra and striatum of PD rats. And its therapeutic mechanism may be associated with increased expression of GDNF.

Objective Present study aimed to characterize the alteration of cortical thickness in first-episode, never-medicated, adult patients with major depressive disorder (MDD), and explore whether such deficits were related with their disease duration and clinical symptom severity. Methods Thirty-seven adult MDD patients were recruited from March 2013 to August 2015 as patient group, and 41 healthy volunteers were as control group. All the patients underwent three-dimensional spoiled gradient recalled (3D-SPGR) sequences, and the images were acquired. Constructions of the cortical surface were developed from 3D-SPGR images using FreeSurfer software, and the thickness of the entire cortex was measured according to the automated surface reconstruction, transformation, and high-resolution inter-subject alignment procedures. Finally, cortical thickness was compared between the two groups, and the relativity between clinical symptom severity, disease progression and clinical scores were analyzed using the General Linear Model (GLM). Results Our results revealed a significant increase in cortical thickness(P<0.05, false discovery rate corrected) in the left anterior and middle cingulate cortex, bilateral precentral cortex, left paracentral cortex, bilateral superior parietal cortex, left temporal pole, and right lateral occipital cortex (cortical thickness 1.89-2.87 mm, cortical volume 34-384 mm2, P<0.05) in MDD patients compared to healthy controls, while no reversed alternation was found. In addition, clinical symptom severity and disease progression showed no correlation with the cortical thickness abnormalities in MDD group(P>0.05). Conclusion Excluding the impact of treatment, our study showed that the cortical thickness change was mainly located in the prefrontal-limbic system in the in early course of MDD.

Objective To detect and explore the expression and clinical significance of dual specificity tyrosine phosphorylation regulated kinase1b (Dyrk1b) in the specimens and cells of cervical lesions. Methods (1)All the data were collected from 75 patients with cervical cancer and 52 cases with squamous intraepithelial lesion(SIL)admitted in the First Affiliated Hospital of Dalian Medical College during Jan. 2011 to Dec. 2013 and confirmed by pathological examination, included 60 cases of stageⅠand 15 cases of stageⅡ, 12 cases with low-grade squamous intraepithelial lesion(LSIL)and 40 cases with high-grade squamous intraepithelial lesion(HSIL). While, 28 cases with chronic cervicitis were chosen as the control group. The protein expression of Dyrk1b was detected by immunohistochemistry among the four groups.(2)The expression of Dyrk1b in HeLa and SiHa cells were detected by western blot method and the expression of Dyrk1b protein were also detected after treatment of AZ191 (5, 10 μmol/L) for 48 hours in HeLa and SiHa cells.(3)The cellular survival and proliferation of HeLa and SiHa cells treated by different concentrations of AZ191(2.5, 5, 10, 25, 50, 100 μmol/L)for 48 hours were detected by methyl thiazolyl tetrazolium (MTT) assay.(4)The rate of apoptosis of HeLa and SiHa cells was detected by flowcytometry after treatment of AZ191 (5, 10μmol/L) for 48 hours. Results (1)The positive rates of Dyrk1b protein in chronic cervicitis, LSIL, HSIL and cervical squamous cancer by immunohistochemistry were 11%(3/28), 1/12, 42%(17/40)and 71%(53/75), respectively. The expression of Dyrk1b in cervical squamous cancer and HISL were higher than those in LSIL and chronic cervicitis (P<0.01), there were significant difference between cervical squamous cancer and HSIL, or between HSIL and LSIL(all P<0.05), while there were not significant difference between LSIL and chronic cervicitis(P>0.05). Expression of Dyrk1b was correlated with stromal invasion depth of cervical cancer (P<0.05), but not with age, clinical stage, lymph node metastasis, and serum squamous cell carcinom antigen(SCC-Ag)levels (all P>0.05). (2) Dyrk1b protein was expressed in different levels in HeLa and SiHa cells, and the expression of Dyrk1b was decreased gradually as the increased of the concentration of AZ191 in both HeLa and SiHa cells by treatment of AZ191 for 48 hours. (3) Different concentration of AZ191 treated on cervical cancer cells could inhibit the cellular proliferation and induce cell apoptosis in a concentration-dependent manner(P<0.01), concomitant to the decreased cell survival rate. The apoptosis rate of HeLa and SiHa were increased significantly after 10μmol/L AZ191-treatment for 48 hours, but no any difference induced by 5 μmol/L AZ191-treatment compared to control group. Also,there was no any difference between Hela and SiHa cells in either inhibitory effect or apoptosis rate induced by AZ191. Conclusions Dyrk1b is over-expressed in either specimens or cells of cervical cancer. The expression of Dyrk1b protein in cervical lesions is increased as the progression of disease. Dyrk1b inhibitor AZ191 could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner in cervical cancer cells.

Objective To discuss the influence of eldepryl on the expressions of glial fibrillary acidic protein (GFAP) and cd11b in substantia nigra and striatum in the rats with Parkinson’s disease (PD),and to clarify the regulatory role of eldepryl in the gliacytes.Methods 72 SD rats were randomly divided into control group,PD model group and eldepryl group,and each group was divided randomly into 4 d and 8 d subgroups (n=12)after the success of model preparation.The PD rat models were established by injecting rotenone in subcutaneous.The number of GFAP and cd11b positive cells and the expressions of GFAP and cd11b were detected by immunohistochemistry and Western blotting method.Results The GFAP and cd11b positive cells were all in a resting state in control group, the GFAP-positive cell body was slender and irregular and had elongated protrusions;the cd1 1 b-positive cell body was small and branch-like,and it had more slender protrusions.The GFAP and cd11b positive cells were all in a active state in model group, the GFAP-positive cell body was hypertrophy, the proj ections increased thickening;the cd1 1 b-positive cell body was more bigger, the proj ections were shorter and thicker, and the number was increased.Compared with model group, the GFAP-positive cell body and protrusions were more slender, the CD11b-positive cell body was more smaller,the projections were more slender,and the number was decreased in eldepryl group.There were a small amount of expression of GFAP and cd11b positive cells in substantia nigra and striatum in the rats in control group,and there was no significant difference between 8 d group and 4 d group(P>0.05). The number of GFAP and cd11b positive cells and the protein expression levels were significantly increased in model group compared with control group(P<0.01);there was more expression in 8 d group compared with 4 d group,but there was no significant difference(P>0.05).The number of GFAP and cd11b positive cells and the protein expression levels in eldepryl group were significantly reduced compared with model group(P<0.01);there were less expression in 8 d group compared with 4 d group, and there was significant difference (P<0.05 ). Conclusion There are activation and proliferation of the gliacytes in substantia nigra and striatum in the rats with PD,and eldepryl can inhibit the activation and proliferation of gliacytes.

Objective To explore the relationship between changes in cortical thickness and single nucleotide polymorphisms(SNPs) in the human leukocyte antigen(HLA) in a group of antipsychotic-naive schizophrenia (AN-SCZ) patients. Methods Twenty-five chronically ill AN-SCZ patients and 51 healthy controls (HCs) were recruited and studied from May 2014 to July 2016. All participants received 3.0 T MR head scans and blood collection to obtain high resolution T1WI images and detailed genetic data. Next, we extracted and averaged the values of cortical thickness from each brain region(n=68) for each participant by FreeSurfer and then used general linear models to explore the relationship of each SNP with cortical thickness in the AN-SCZ and HCs while including age, gender and duration of disease in the models as covariates. In the next step,we applied an independent-samples t-test with a threshold of 0.05 to explore whether the cortical thicknesses differed significantly between the AN-SCZ and HCs in the brain regions that were significantly associated with the SNPs in the MHC. Finally, we examined the correlation of clinical symptoms with cortical thickness in the above brain areas in the whole AN-SCZ group using Pearson correlation tests. Results Seven of the 11 SNPs within the HLA regions exhibited significant associations with the cortical thickness only in the AN-SCZ patients, including rs1635, rs1736913, rs2021722, rs204999, rs2523722, rs3131296 and rs9272105. Furthermore, the AN-SCZ patients also exhibited significant reductions in cortical thickness in the above brain regions, which included the left entorhinal cortex, the left pars triangularis cortex, the left rostral middle frontal cortex, the right lateral occipital cortex, the right medial orbitofrontal cortex, the gray matter surrounding the right calcarine gyrus, the right rostral middle frontal cortex, the right frontal pole and the caudal part of the right anterior cingulate. The left entorhinal region also exhibited a negative correlation with PANSS activation scores in the AN-SCZ(r=-0.601, P=0.03). Conclusion The present study provided evidence for the significant association of HLA risk variants with cortical thickness in AN-SCZ.

Objective To investigate the cognition influencing factors of regular laboratory monitoring of HBeAg negative in chronic HBV infection,and analyze the related factors of HBeAg conversion. Methods From January 2015 to March 2017,a total of 302 chronic HBV infected patients in Jinin Infectious Disease Hospital were investigated with a questionnaire about disease related cognition. Single factor and multiple factors Logistic regression analysis was used to analyze the influencing factors of regular monitoring behavior and HBeAg conversion. At the same time,163 cases of HBeAg negative HBV infection were divided into the two groups: regular and irregular monitoring, and disease related laboratory tests and the outcomes were analyzed. Results Psychological pressure(OR = 4. 339, 95％ CI:1. 322 - 14. 243),antiviral treatment( OR = 5. 149,95％ CI:1. 628 - 16. 283),knowledge of hepatitis B (OR = 3. 306,95％ CI:1. 108 - 9. 867) and the stability of disease(OR = 3. 229,95％ CI:1. 094 - 9. 528) were the regular monitoring promoting factors(all P < 0. 05). Antiviral therapy(OR = 0. 298,95％ CI:0. 108 - 0. 822),virus gene mutation(OR = 0. 202,95％ CI:0. 048 - 0. 856),and duration of disease(OR = 0. 340,95％ CI:0. 122 - 0. 949) were related factors of HBeAg conversion(all P < 0. 05). The serum levels of ALT,ALB,AFP and HBV - DNA in the HBeAg negative regular monitoring group were (68 ± 34) IU/ L, (40 ± 12) g/ L, (23. 0 ± 5. 9) μg/ L, (2. 0 ± 1. 3)copies/ mL,respectively,which in the non - regular monitoring group were (126 ± 56) IU/ L,(35 ± 10) g/ L, (78. 0 ± 12. 8)μg/ L,(3. 9 ± 1. 7) copies/ mL,respectively,the differences were statistically significant (t = 2. 323, 2. 097,2. 109,2. 234,all P < 0. 05). Conclusion HBeAg negative patients is a key group to monitor and control disease progression. Regular laboratory monitoring is better. Medical staff should enhance patients' cognition education and improve disease control rate.

Objective:To explore the efficiency of MR psychoradiology examination in screening and classification of psychiatric disorders as well as its potential clinical application.Methods:Retrospective study was conducted for 144 patients with MR psychoradiology examination, who were diagnosed mental disorders based on International Statistical Classification of Diseases and Related Health Problems Tenth Revision (ICD-10) from September 2018 to July 2020 in West China Hospital of Sichuan University. As our previous studies, imaging diagnostic models were constructed based on gray matter volume (GMV) analysis for four kinds of psychiatric disorders, including depression, anxiety disorder, bipolar disorder and schizophrenia. For 120 patients with psychiatric disorders, the GMV change pattern of brain regions was detected and subtyped by MR psychoradiology examination with 50% similarity threshold of the above imaging diagnostic models. The diagnostic efficiency of MR psychoradiology examination was evaluated with references of clinical diagnose. For 24 patients with dementia, brain atrophy was additionally measured by conventional MR examination and MR psychoradiology examination respectively.Results:The sensitivity, specificity, Youden index and accuracy of MR psychoradiology in identifying the four psychiatric disorders were 86.6% (84/97), 69.6% (16/23), 0.56 and 83.3% (100/120), including depression [77.8% (28/36), 69.0% (58/84), 0.47, 71.7% (86/120)], schizophrenia [58.8% (10/17), 91.3% (94/103), 0.50, 86.7% (104/120)], bipolar disorder [42.1% (8/19), 96.0% (97/101), 0.38, 87.5% (105/120)] and anxiety disorder [24.0% (6/25), 100% (95/95), 0.24, 84.2% (101/120)]. As for 24 patients with dementia, 58.3% (14/24) were detected with brain atrophy by conventional MR examination, while 91.7% (22/24) were detected by MR psychoradiology examination.Conclusions:MR psychoradiology can detect the subtle brain structural abnormalities of patients with mental disorders. Although it can′t be used as an independent biomarker for disease diagnosis till now, it is of great help in improving the accuracy and objectivity of diagnosis.

Objective To investigate the varying variances of the genetic components in birth cohorts.Methods Twin samples used in the current study were collected from the Chinese National Twin Registry and a two-wave study was conducted,in Qingdao and Lishui regions.Samples were broken down by birth cohort to create four subgroups:-1958,1959-1961,1962-1970 and 1970-.Structural equation models were fitted in each subgroup to estimate the genetic and environmental variances.Results From each birth cohort,weight and body mass index in 2012 appeared higher than those in 2001.Twins of 1971-cohort subgroup showed lower weight than in the other cohort subgroups.Except for the 1959-1961 cohort subgroup,the later birth cohorts were inversely related to the body mass indexes.Genetic factors might explain 54％-76％ of the total variations on the body mass index.Heritability of body mass index of twins born during 1959-1961 was increasing along with age.Conclusion Genetic factors might explain the main portion which related to the phenotypic variance of body mass index.Effects of genetic factors on body mass index of twins born during 1959-1961 might have increased along with age.

Objective: To investigate genotypes and drug susceptibility of the 100 strains of Candida glabrata isolated from 100 women (including 50 pregnant women) in order to study the drug-resistance and gene polymorphism, and to investigate the correlation of drug-resistance, gestation and gene polymorphism. Methods: Multilocus sequence typing (MLST) technique was introduced to identify sequences of 6 housekeeping genes from 100 isolates of Candida glabrata. The results were compared with sequence information in MLST databases by Clustalx software to determine a strain allelic profile and sequence type (ST). Drawing the phylogenetic tree by weighted paired group average method and the minimal spanning tree method of MEGA6.0 software, the microevolution and relationship between different strains were analyzed. ATB FUNGUS semi-automatic system was used to test the drug susceptibility. Fisher analysis method was used to analyze the correlation between the genotypes and pregnancy.Ridit analysis method was used to analyze the correlation between the genotypes and drug susceptibility. Results: The 100 isolates belonged to 34 clone sequences. There were 53 isolates belonged to ST-7 ( 26 isolates of pregnancy), 7 isolates belonged to ST-3 (3 isolates of pregnancy), 6 isolates belonged to ST-19 (5 isolates of pregnancy ), 3 isolates belonged to ST-15 (1 isolate of pregnancy), 2 isolates belonged to ST-10 (2 isolates of pregnancy), 1 isolate belonged to the other types of ST. Total of 100 isolates of Candida glabrata were 100% sensitive to fluorocytosine and amphotericin. The effect of itraconazole was poor with the sensitive rate of 20%. The resistance rates of fluconazole and voriconazole were 4% and 1% respectively. All genotypes were sensitive to voriconazole except ST-X1. In the correlation between genotype and itraconazole resistance, ST-7 as the standard group, the Ridit values in the group of ST-15, ST-19 and other types of ST were not included the mean Ridit value of the standard group in itraconazole (0.5). The system evolution tree was built using the neighbor-joining method (NJ) . All genotypes could be divided into 3 groups, as Ⅰ, Ⅱ, Ⅲ. Group Ⅰ had 44 cases, group Ⅱ had 53 cases , group Ⅲ had 3 cases . All the collected clinical strains had small genetic distances during molecular evolution. Conclusions ST-7 was the dominant genotype in Guiyang. No correlation between different STs and patients′ pregnancy was found. The different drug susceptibility in itraconazole between ST-7, ST-15, ST-19 and other STs were found. The Candida glabrata associated with VVC showed highly discrimative diversity. However, the phylogenic analysis exhibited genetic similarity among the strains studied.(Chin J Lab Med, 2018, 41: 596-600)