Role of NRF2 signaling pathway in trichloromethane-induced oxidative stress in L02 cells / 中国职业医学

@#Objective - （ ） To investigate the effects of nuclear factor erythroid 2 related factor 2 NRF2 on the oxidative stress （ ） Methods ） ，， induced by trichloromethane TCM in human normal hepatocyte L02 cells. i L02 cells were stimulated with 1 2 ， ， ， （ ）， 4 8 12 16 and 20 mmol/L TCM solution dissolved in dimethyl sulfoxide and the control group and blank group were set ， - ， up. After culturing for 24 hours the cell viability was detected by CCK 8 colorimetric method and the concentration of TCM ） -， - stimulation was screened. ii L02 cells in logarithmic growth phase were randomly divided into control group and low medium - ， ， ， and high dose groups. After 24 hours of exposure to 0 4 8 and 12 mmol/L TCM the cells were collected. The activity of （ ）， （ ）， （ - ） （ ） superoxide dismutase SOD catalase CAT glutathione peroxidase GSH Px and the level of malondialdehyde MDA NRF2， - （HO-1）， were detected by colorimetric analysis. The mRNA expression levels of heme oxygenase 1 glutamate cysteine （GCLC） （） （NQO1） - ligase catalytic subunit and NAD P H quinone dehydrogenase 1 were detected by real time fluorescence ， - ， polymerase chain reaction. The protein levels of NRF2 HO 1 GCLC and NQO1 were detected by Western blotting.Results ） ， ， ， ， i When the concentration of TCM was 4 8 12 16 and 20 mmol/L the survival rate of L02 cells decreased （ P ） ， ， significantly compared with the control group all <0.05 . The concentration of 0 4 8 and 12 mmol/L were selected as the ） ， - stimulation doses for subsequent experiments. ii Compared with the control group the activities of SOD and GSH Px in L02 （ P ） （ P ）， - cells in the three doses groups decreased all <0.05 and the levels of MAD increased all <0.05 with a dose effect - （P ）， relationship. The CAT activity of L02 cells in the medium dose group was lower than that in the control group <0.05 and the - （ P ） CAT activity of L02 cells in the high dose group was lower than that in the others three groups all <0.05 . Compared with the ， NRF2 - （P ），NRF2 control group the relative expression levels of mRNA in L02 cells in the low dose group decreased <0.05 - （P ）， NRF2 mRNA in L02 cells in the medium dose group increased <0.05 mRNA and NRF2 protein expression in L02 cells in （ P ） HO-1，GCLC， NQO1 ， the highdose group increased both <0.05 . The relative expression level of mRNA and GCLC NQO1 （ P ） protein expression in L02 cells in the three doses groups increased compared with the control group all <0.05 . The relative NRF2 - - - expression level of mRNA in L02 cells in the high dose group was higher than that in the low and medium dose groups （ P ）， - （P ）， both <0.05 and the relative expression of NRF2 protein was higher than that in the low dose group <0.05 but the HO-1 GCLC - - （ relative expression levels of and mRNA and HO 1 protein level were lower than those in the medium dose group all P ）Conclusion - <0.05 . TCM exposure can inhibit the proliferation of L02 cells by inducing oxidative stress with a dose effect ， relationship. In this process the antioxidant mechanism mediated by NRF2 was activated. The expression of antioxidant defense ， - ， and detoxification related target genes downstream of NRF2 signaling pathway was activated and the expression of HO 1 - GCLC and NQO1 was up regulated to alleviate the oxidative damage caused by TCM.

Analysis of prognostic factors in children with acute myeloid leukemia(M4/M5) / 中华实用儿科临床杂志

Objective To investigate the clinical efficacy and prognostic factors for M4/M5subtypes in chil-dren with acute myeloid leukemia(AML).Methods A retrospective analysis of the clinical data of M4/M5subtypes in Shanghai Children′s Hospital Affiliated to Shanghai Jiaotong University,from January 2009 to December 2014 was carried out.The long-term efficacy,prognosis and relapse factors were analyzed.Results The clinical data of 46 ca-ses were collected,among which 38 cases were treated with more than 2 courses,including 22 male,16 female,19 cases M4and 19 cases M5.The median age was 5 years.5-year overall survival(OS)rate and 5-year event-free survival (EFS)rate were(57.7 ± 9.3)% and(47.2 ± 8.9)%,and 5-year EFS of M4and M5were(52.4 ± 12.7)% and (45.4 ± 11. 9)%. Compared with the international risk stratification:5-year EFS rate of favorable-risk, intermediate-risk and poor-risk were(77.2 ± 12.4)%,(49.5 ± 14.9)% and(25.0 ± 19.8)%(χ2=6.305,P=0.043).Single factor analysis showed that extramedullary infiltration(χ2=4.828,P=0.028),Chromosome karyotype (χ2=10.178,P=0.017),the eighth day assessment(χ2=5.382,P=0.020)and course of treatment(χ2=4.771, P=0.029)were prognostic factors;multivariate analysis showed extramedullary infiltration(HR =5.323,95%CI:1.620-17.490,P=0.006)and less-than-6 courses of treatment(HR=6.186,95%CI:1.726-22.176,P=0.005)were the independent risk factors of affecting survival.Conclusions (1)Strengthening treatment and ade-quate courses of treatment are the critical to improve the overall curative effect in children with M4/M5subtypes.(2) Extramedullary infiltration was the risk factor for survival and recurrence in M4/M5subtypes.(3)It is suggested that the children who have the initial symptoms and molecular biology with poor prognostic factors choose hematopoietic stem cell transplantation as early as possible.

Related factors of aggressive behavior among school aged children in Nanjing / 中国心理卫生杂志

Objective:To study the distribution and related factors of aggressive behavior among school aged children in Nanjing.Methods:Totally 4678 primary school students in Nanjing were sampled by cluster random sampling in this study.The General questionnaire and Achenbach's child Behavior Checklist were used to investi gate the general situation and aggressive behavior.Results:The rate of aggressive behavior of school-age children in Nanjing was 3.6 ％ (167/4678).Multivariate logistic regression analysis indicated that democratic parenting style [other parenting styles (OR =1.94,95％ CI =1.10-3.42),mixed parenting style(OR =1.96,95％ CI =1.35-2.85)],and genetic screening before birth (OR =0.71,95％ CI =0.52-0.99) were protective factors for children's aggressive behavior.The factor figures of aggressive behavior were positively correlated with that of oth er behavior problems in Pearson correlation analysis (r =0.52-0.80,Ps ＜0.01).Conclusion:About 3.6％ of the school aged children in Nanjing have aggressive behavior.It is more likely to have aggressive behaviors for children who is in other parenting styles except the democratic style and never have the genetic screening before birth.And children who with aggressive behavior may co-occur with other behavior problems.

Two-year follow-up study of white matter structures in 2-3 years old children with autism spectrum disorder / 中华实用儿科临床杂志

Objective To explore the developmental characteristics of white matter volume in autism spectrum disorder (ASD) children longitudinal.Methods From May 2011 to September 2014,37 ASD children (ASD group)and 27 developmental delays (DD) children (control group) were treated at the Child Mental Health Research Center,Nanjing Brian Hospital Affiliated of Nanjing Medical University,and the children whose age,gender and developmental quotient matched with the ASD children were scanned by structure magnetic resonance imaging (sMRI) at the age of 2-3 years old and 4-5 years old respectively.Region of interest (ROI) technology was adopted to investigate the change of the cerebrum white and the sub-lobes structure white matter volume with time.Then the correlation between clinical symptoms and brain white matter volume changes was analyzed.Results Among the 2-3 years old,compared with the control group,the white matter volume of the total brain[(383 521.84 ±6 427.57) mm3 vs.(364 014.06 ±6 856.97) mm3],the left cerebral hemisphere [(191 609.35 ± 3 206.60) mm3 vs.(181 695.89 ± 3 389.54)mm3],temporal lobe [(41 860.49 ±816.38) mm3 vs.(39 444.18 ± 834.85) mm3] and the right temporal lobe [(21 312.79 ± 414.07) mm3 vs.(20 084.22 ± 412.13) mm3] were significantly larger in the ASD group,and the differences were statistically significant (all P ＜ 0.05).With the analysis of covariance with age or the total brain volume as the covariate,the differences disappeared(all P ＞ 0.05).Among the 4-5 years old,compared with the control group,the white matter volumes of the total brain[(417 651.42 ± 6 443.86) mm3 vs.(394 317.27 ± 6 404.86)mm3],left cerebral hemisphere [(208 714.16 ±3 214.61) mm3 vs.(197 192.82 ±3 262.02) mm3],right cerebral hemisphere [(208937.26±3242.09) mm3 vs.(7 124.45 ±3 193.13) mm3],frontal lobe [(107 107.46±1 681.99) mm3 vs.(100 326.19 ± 1 883.24) mm3],left frontal lobe [(54 569.63 ± 846.85) mm3 vs.(51 177.25 ±979.09) mm3],right frontal lobe [(52 537.83 ± 841.99) mm3 vs.(49 148.94 ±928.31) mm3],temporal lobe [(45 189.75 ± 833.29) mm3 vs.(42 487.73 ± 786.27) mm3],left temporal lobe [(22 204.21 ±411.77) mm3 vs.(20 922.90 ± 418.46) mm3],and right temporal lobe [(22 985.54 ± 426.93) mm3 vs.(21 564.83 ± 378.78) mm3]were significantly larger in the ASD group,and the differences were statistically significant (all P ＜ 0.05).With the analysis of covariance with age as the covariate,the differences still existed (all P ＜ 0.05).With the analysis of covariance with the total brain volume as the covariate,the differences disappeared (all P ＞ 0.05).For longitudinal analysis,there was a significant difference in the white matter volume between the whole brain,left cerebral hemisphere,right cerebral hemisphere,frontal lobe,left frontal lobe,fight frontal lobe,temporal lobe,left temporal lobe,right temporal lobe and the differences were statistically significant (F =5.521,5.533,5.459,5.830,5.800,5.723,4.857,4.418,5.159,all P ＜0.05).There was a positive correlation between the changes of the volume of whole brain,the white matter volume in the whole brain,bilateral cerebral hemisphere,frontal lobe,parietal lobe,right parietal lobe and Childhood Autism Rating Scale (r =0.367,0.343,0.321,0.349,0.296,0.308,0.351,all P ＜ 0.05).Conclusions Among the 2-3 years old,the white matter volume of the brain regions have been increased significantly in ASD.Among the 4-5 years old,the increase of the white matter volume of the brain regions implicated more widely which mainly concentrated in the frontal and temporal lobe in ASD.The severity of the clinical symptoms of ASD may be associated with the white matter volume of the total brain,bilateral cerebral hemisphere,frontal lobe,parietal lobe and right parietal lobe.

Highly Sensitive and Specific Detection of SRY Gene for Non-invasive Prenatal Diagnosis / 分析化学

By detecting SRY gene of cell-free fetal DNA ( cffDNA) in maternal peripheral blood, the sex of fetuses was determined, the risks of sex-linked genetic disorders were assessed and the birth rate of sick fetuses was decreased. A method of real-time polymerase chain reaction ( PCR) coupled with invader assay was established to detect SRY gene. This method possessed the advantages such as high sensitivity, high specificity and non-contaminated with closed tube detection. Under the optimized reaction conditions such as 250 nmol/L detection probes, 7. 5 U FEN1 enzyme, 0. 5 U Taq polymerase and 67℃ of annealing temperature in pre-amplification, the simulated samples as low as 4% ( 4 copies/μL ) were detected and two clinical samples with the gestation age of 9 weeks and 10 weeks were successfully detected. The detection results showed that this method could be used to detect SRY gene of cffDNA in maternal peripheral blood, providing an effective technique for clinical non-invasive prenatal diagnosis based on SRY gene.

Highly Sensitive and Specific Detection of SRY Gene for Non-invasive Prenatal Diagnosis / 分析化学

By detecting SRY gene of cell-free fetal DNA ( cffDNA) in maternal peripheral blood, the sex of fetuses was determined, the risks of sex-linked genetic disorders were assessed and the birth rate of sick fetuses was decreased. A method of real-time polymerase chain reaction ( PCR) coupled with invader assay was established to detect SRY gene. This method possessed the advantages such as high sensitivity, high specificity and non-contaminated with closed tube detection. Under the optimized reaction conditions such as 250 nmol/L detection probes, 7. 5 U FEN1 enzyme, 0. 5 U Taq polymerase and 67℃ of annealing temperature in pre-amplification, the simulated samples as low as 4% ( 4 copies/μL ) were detected and two clinical samples with the gestation age of 9 weeks and 10 weeks were successfully detected. The detection results showed that this method could be used to detect SRY gene of cffDNA in maternal peripheral blood, providing an effective technique for clinical non-invasive prenatal diagnosis based on SRY gene.

Influence of Positive Psychological Quality on Quality of Life of Rural Left-behind Elderly / 中国康复理论与实践

Objective To explore the influence of positive psychological quality on the quality of life of rural left behind elderly. Meth-ods 356 rural left behind elderly in Bengbu and Huaibei cities of Anhui province were investigated with WHO Quality of Life-BREF (WHO-QOL-BREF), Chinese version of the Meaning in Life Questionnaire (C-MLQ), Purpose-in-Life Test (PIL) and Index of Well-Being (IWB). Results The scores of WHOQOL-BREF in physical, psychological, social relations and environment are significantly lower in the rural left behind elderly than in the norm in China (t>3.105, P<0.001). The scores of WHOQOL-BREF of the left behind elderly in rural areas signifi-cantly correlated with the sense of life meaning, life objective and subjective well being (P<0.05). The quality of life of left behind elderly in rural areas was analyzed by regression analysis, age, health status, education and other demographic variables and life goals, life sense, sense of autonomy, etc. entered the regression equation (P<0.05). The structure model analysis showed that the life meaning and purpose of life were the important factors that affected the quality of life of rural left behind old people, in which the subjective well-being played a meditational role. Conclusion The positive psychological quality of life meaning, life purpose and other positive psychological qualities sig-nificantly impact the quality of life of rural left behind elderly, and should carry out targeted mental health guidance.

Effect of livin-modified BM-MSCs transplantation on cardiac function fol-lowing acute myocardial infarction in a rat model / 中国病理生理杂志

[ ABSTRACT] AIM:To study the effect of livin gene-modified bone marrow mesenchymal stem cells ( BM-MSCs) transplantation on the cardiac function following acute myocardial infarction in a rat model and the expression of livin , caspase-3, caspase-7 and caspase-9 in the livin gene-modified BM-MSCs.METHODS: The MSCs were obtained by the whole bone marrow culture method , and the apoptosis of the MSCs after infection with adenovirus vector carrying enhanced green fluorescent protein ( EGFP) gene and livin recombinant vector ( rAd-livin) were detected by flow cytometry .The ex-pression of livin, caspase-3, caspase-7 and caspase-9 was detected by Western blot .After permanent left anterior descend-ing artery occlusion , the rats were randomized to receive intramyocardial injection of DMEM without cells ( vehicle group ) , or containing MSCs ( MSCs group ) , MSCs ( EGFP ) ( rAd-control/MSCs group ) or MSCs ( livin ) ( rAd-livin/MSCs group).Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), the maximum in-creased rate of left ventricular pressure ( -dp/dtmax ) and the maximum decline rate of left ventricular pressure ( +dp/dtmax ) were recorded for evaluating the cardiac functions .RESULTS: The apoptosis of rAd-livin/MSCs was significantly decreased as compared with MSCs and rAd-control/MSCs (P<0.05).Meanwhile, the expression of caspase-3, caspase-7 and caspase-9 was significantly downregulated as compared with the other 2 groups ( P<0.05 ) .The cardiac function in rAd-livin/MSCs group was significantly improved as compared with DMEM group , and those in the other 2 groups got the similar results, but the function in rAd-livin/MSCs group was better improved .Meanwhile, the number of surviving cells in rAd-livin/MSCs group was significantly improved as compared with the other 2 groups .CONCLUSION:The apoptosis of MSCs is decreased after rAd-livin transfection, and the expression of caspase-3, caspase-7 and caspase-9 is also significant-ly downregulated while the expression of livin is significantly upregulated .Transplantation of livin-modified BM-MSCs by lentiviral vector results in better prognosis for treating myocardial infarction by enhancing cell survival .

The study on Ezscan screening for dysglycaemia in Chongqing area / 重庆医学

Objective To assess the screening capacity of Ezscan for abnormal glucose metabolism .Methods A total of 1 732 permanent residents of Chongqing city underwent physical examination from August 2013 to August 2014 were selected as subjects ,questionnair survey ,physical examination and Ezscan measurement were performed .Additionally ,the levels of fasting blood‐glucose(FPG) ,OGTT 2h blood glucose ,HbA1c and serum lipid were detected .Results The prevalence rate of abnormal glucose metabolism for residents with high Ezscan score was higher than that in those with low Ezscan score .The AUC of Ezscan screening for abnormal glucose metabolism was 0 .616 ,the optimum diagnosis tangent point was 24 .0% ,the sensitivity was 67 .0% .The optimum diagnosis tangent point of FPG was 5 .5 mmol/L for abnormal glucose metabolism ,the sensitivity and speci‐ficity was 70 .5% and 61 .7% respectively ,and the AUC was 0 .824 .The sensitivity of FPG for screening abnormal glucose metabo‐lism was 47 .2% ,when the cut‐off value of FPG was 6 .1 mmol/L .Conclusion The sensitivity of Ezscan for screening abnormal glucose metabolism is higher than that of FPG (when the cut‐off value was 6 .1 mmol/L) ,Ezscan can be used as an efficiency meth‐od for early detection of abnormal glucose metabolism in the asymptomatic population .

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43 (cx43)

Objective To explore the effect and mechanism of angiotensin II receptor blockers – Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan + ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group (SO), myocardial infarction group (MI), Irbesartan group and MI + Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mRNA and protein level. Results The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia (P < 0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group (P < 0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arrhythmia between MI group and SO group (P < 0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group (P < 0.05). There was the significant difference in the overall score between MI + Irbesartan group and MI group (P < 0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased (P < 0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43 (cx43)

OBJECTIVE@#To explore the effect and mechanism of angiotensin II receptor blockers - Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia.@*METHODS@#Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan + ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43 (Cx43) mRNA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group (SO), myocardial infarction group (MI), Irbesartan group and MI + Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mRNA and protein level.@*RESULTS@#The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia (P < 0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group (P < 0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arrhythmia between MI group and SO group (P < 0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group (P < 0.05). There was the significant difference in the overall score between MI + Irbesartan group and MI group (P < 0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased (P < 0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan.@*CONCLUSIONS@#Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.

Clinical significance of serum fibrosis markers in diagnosis of infantile hepatitis syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the correlation between four serum fibrosis markers and liver function in patients with infantile hepatitis syndrome (IHS), and to explore the clinical significance of these markers in the diagnosis of IHS and the assessment of disease severity.</p><p><b>METHODS</b>A retrospective study was performed on 60 patients with IHS who were divided into hepatic fibrosis and normal groups based on ultrasound diagnosis. Levels of four liver fibrosis markers, i.e., hyaluronic acid (HA), type III procollagen (PC-III), type IV collagen (IV.C), and laminin (LN), were compared between the two groups, and the correlation between these markers and liver function was analyzed.</p><p><b>RESULTS</b>Levels of liver function markers (alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), total bilirubin (TBil), direct bilirubin (DBil), indirect bilirubin (IBil), and total bile acid (TBA)) in the hepatic fibrosis group were significantly higher than those in the normal group (P<0.05). Levels of HA and IV.C in the hepatic fibrosis group were significantly higher compared with those in the normal group (P<0.05). Furthermore, HA, IV.C, and PC-III levels were positively correlated with those of ALT, TBil, GGT, DBil, IBil, and TBA (r=0.25-0.49), and the strongest correlation existed between HA/IV.C and ALT/jaundice markers.</p><p><b>CONCLUSIONS</b>Assay measuring serum fibrosis markers (HA, IV.C, and PC-III) in combination with liver function tests and ultrasound examination has an important clinical value in the early diagnosis of IHS and evaluation of disease severity.</p>

Clinical diagnosis and mutation analysis of a Chinese boy with Phelan-McDermid syndrome / 中华实用儿科临床杂志

Objective To explore the clinical features and genetic diagnosis analysis of a Chinese boy with unexplained overgrowth and developmental delay.Methods The clinical symptoms of the boy were described,and performed routine G-banding was performed to analyze the karyotype of the patient,and multiplex ligation-dependent probe amplification (MLPA) was used to detect the copy number variation (CNVs) in the 22q13 region,and array-comparative genomic hybridization(array CGH) was used to detect all chromosome abnormally,then fluorescence in situ hybridization(FISH) confirmed the result.Results 1.The boy was 1.5 years old and complained about accelerated growth,global developmental delay,severely delayed speech ability and peculiar facial features.2.Routine karyotype analysis showed a karyotype of 46,XY.MLPA found terminal deletion with breakpoints within the SHANK3 gene and ACR gene,RABL2B gene,and array CGH finely mapped the deletion on 22q13,furthermore FISH confirmed the micro deletion.Conclusions Combining the clinical manifestations and effective examination of 22q13 deletion,the boy got a reliable diagnosis of Phelan-McDermid syndrome;as array CGH can be useful to screen CNVs of all chromosome,so MLPA should be applied to some special CNVs.

Roles of targeting Ras/Raf/MEK/ERK signaling pathways in the treatment of esophageal carcinoma / 药学学报

Ras is best known for its ability to regulate cell growth, proliferation and differentiation. Mutations in Ras are associated with the abnormal cell proliferation which can result in incidence of all human cancers. Extracellular signal-regulated kinase (ERK) is a downstream effector of Ras and plays important roles in prognosis of tumors. Recently, evidence has gradually accumulated to demonstrate that there are other effectors between Ras and ERK, these proteins interact each other and constitute the thorough Ras/Raf/MEK/ERK signaling pathway. The pathway has profound effects on incidence of esophageal carcinoma and clinical applications of some chemotherapeutic drugs targeting the pathway. Further understanding of the relevant molecular mechanisms of Ras/Raf/MEK/ERK signaling pathway can be helpful for the development of efficient targeting therapeutic approaches which contribute to the treatment of esophageal cancer. In this article, roles of Ras/Raf/MEK/ERK signaling pathway in esophageal carcinoma as well as pharmacological targeting point in the pathway are reviewed.

Relationships between suicide attitudes and perception of life purpose and meaning of life in college students / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the suicide attitudes of college students and analyze the impact of the perception of life purpose and meaning of life on their suicide attitudes using structural equation modeling.</p><p><b>METHODS</b>A total of 1050 college students were tested by Suicide Attitude Questionnaire (QSA), Purpose in Life test (PIL) and Chinese version of Meaning of Life questionnaire (C-MLQ). A theoretical model was established for confirming the influence of the purpose in life and meaning in life on suicide attitudes of the college students.</p><p><b>RESULTS</b>The college students had generally a negative attitude towards suicide. The female students tended to show more objective attitudes towards suicide and the students from rural areas had a stronger attitude against euthanasia.The meanings and purposes in life were closely correlated with the attitudes towards suicide, and the structural equation modeling well fitted the data (Χ(2)/df=1.924, GFI=0.936, AGFI=0.915, NFI=0.937, CFI=0.940, and RMSEA=0.045). The perception of meaning and purposes in life had a direct predictive value on the suicide attitude of the college students, and the presumptions derived from the theoretical model were strongly supported by structural equation modeling.</p><p><b>CONCLUSIONS</b>The perceptions in meanings in life and purposes in livelihood have important influence on the suicide attitudes of college students, and intervention with effective life education should be administered to guide the suicide attitude of the college students.</p>

Synergistic effects from substrate stiffness and cytokine TGF-β1 on phenotypic transformation of hepatocytes / 医用生物力学

Objective To explore the synergistic effects of substrate stiffness and cytokine TGF-β1 on phenotypic transformation of hepatocytes by establishing an in vitro culture model with the substrate stiffness that is relevant to hepatic cells physiologically and pathologically. Methods Immunofluorescence and Western blotting were adopted to observe the morphological adjustment, motion characteristics, cytoskeleton arrangement of hepatocytes on polyacrylamide substrates with different stiffness, as well as the changes in expression of integrin and phenotypic markers E-cadherin, albumin and alpha-smooth muscle actin (α-SMA). Image analysis software was also used for quantitative study on the obtained data. Results On the 3.6 kPa substrates, the scattered single cells were actively deformed and relocated, but the bulk cell population had little change in polarization and microfilament organization. Muscle actin was assembled as cortical ring in cell periphery. There was more abundant expression of E-cadherin and albumin, but less expression of integrin and α-SMA in TGF-β1 treated group as compared to the control group. On the 30 kPa substrates, the motion and deformation of cells were not so active, and expression of both E-cadherin and albumin in TGF-β1 treated group was decreased, while that of α-SMA was increased as compared to the control group. For 30 kPa and 3.6 kPa control groups and 30 kPa and 3.6 kPa TGF-β1 treated groups, expression of both E-cadherin and albumin was reduced (P<0.05), but that of alpha-SMA was increased (P<0.05), while no significant differences were found in both 10 kPa control group and TGF-β1 treated group, as well as in 30 kPa and 3.6 kPa control groups and TGF-β1 treated groups. Conclusions The increase of substrate stiffness can induce transformation of hepatocyte phenotype and promote the influence of TGF-beta 1 on behavior of hepatocyte metabolism.

Copy-number variations of SHANK3 and related clinical phenotypes in children with autism / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore possible relationship between copy-number variations (CNVs) in 15q11-13, 16p11 and SHANK3 gene by using multiplex ligation-dependent probe amplification (MLPA) and the phenotypes in children with autism and to further explore the clinical application of MLPA to make an etiological diagnosis of Autism.</p><p><b>METHODS</b>The diagnosed of autism was made according to the criteria of the ICD-10 and DSM-IV, with typical cluster of symptoms comprise social disability, communication impairments and repetitious behaviors. MLPA KIT P343-C1 AUTISM-1 was used to detect and describe the incidence of CNVs in these three domains.</p><p><b>RESULTS</b>Among 109 cases collected from 102 autistic pedigrees, 2 individuals had SHANK3 microdeletion, accounting for approximately 2% (2/109) of cases, suggesting the proportion of SHANK3 microdeletion might contribute to typical autism. The phenotypic traits of patients with SHANK3 microdeletions showed homogenicity in severe core symptoms and mental retardation.</p><p><b>CONCLUSIONS</b>SHANK3 microdeletion is an important genetics component for autism, which may explain 2% typical autism cases. SHANK3 microdeletion might explain autistic core symptoms and mental retardation. MLPA is a sensitive and a high throughput technique to detect CNVs in specific DNA segments, which is beneficial for further investigation of etiology of autism.</p>

Effects of substrate stiffness on the migration of hepatic and hepatoma carcinoma cells / 医用生物力学

Objective To investigate the cause of tumor cell migration by comparing the effect of substrate stiffness on hepatic and hepatoma carcinoma cell migration so as to understand the invasive characteristics of tumor cells. Methods Immunofluorescence staining, morphological analysis and transwell were employed to observe the morphological characteristics of HCCLM3 and L02 cells on different substrates and test their migration characteristics with the quantitative analysis. Results (1) The migration rate and net translocation of HCCLM3 and L02 cells on 4 kPa substrate was higher than those both on 0.5 kPa(most soft one) and on glass (the hardest one) substrates, and L02 cells also displayed higher migration efficiency than HCCLM3 cells on such substrates. (2) The mean squared displacement of HCCLM3 and L02 cells on different substrates showed consistent tendency, and the directional persistence of L02 cells on the softer substrate was significantly higher than that of HCCLM3 cells. (3) In 0.5 and 1 mg/mL three dimensional collagen environment, the number of invasive cells of HCCLM3 was remarkably more than that of L02 cells. After adding MMPs inhibitor GM6001 (40 μg/mL), the number of invasive cells was notably increased in HCCLM3 cells, but notably decreased in L02 cells. Conclusions (1) In two dimensional comparatively soft environment, L02 cells displayed an efficient migration due to its higher directional persistence. (2) In three-dimensional collagen environment, the invasion efficiency of HCCLM3 cells was significantly higher due to the various modes of migration adaptation to the microenvironment.

Picture perception in Chinese dyslexic children: an eye-movement study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Currently, whether or not there is visuospatial impairments in Chinese dyslexic children is still a matter of discussion. The relatively recent application of an eye-tracking paradigm may offer an opportunity to address this issue. In China, in comparison with reading studies, there have not been nearly as many eye movement studies dealing with nonreading tasks such as picture identification and whether Chinese children with dyslexia have a picture processing deficit is not clear. The purposes of the present study were to determine whether or not there is visuospatial impairments in Chinese dyslexic children. Moreover, we attempted to discuss whether or not the abnormal eye movement pattern that dyslexic subjects show during reading of text appropriate for their age is a consequence of their linguistic difficulties.</p><p><b>METHODS</b>An eye-link II High-Speed Eye Tracker was used to track the series of eye-movement of 19 Chinese dyslexic children and 19 Chinese normal children. All of the subjects were presented with three pictures for this eye-tracking task and 6 relative eye-movement parameters, first fixation duration, average fixation duration, average saccade amplitude, mean saccade distance, fixation frequency and saccade frequency were recorded for analysis.</p><p><b>RESULTS</b>Analyzing the relative parameter among three pictures, except for the fixation frequency and the saccade frequency, other eye-movement parameters were significantly different among the three pictures (P<0.05). Among the three pictures, the first fixation duration was longer, and the average fixation duration, the average saccade amplitude and the mean saccade distance were shorter from picture 2 to picture 3. Comparing all eye-movement parameter between the two groups, the scores of average saccade amplitude (P=0.017) and the mean saccade distance (P=0.02) were less in the dyslexia group than in the normal group (P<0.05), other parameters were the same in the two different groups (P>0.05).</p><p><b>CONCLUSIONS</b>The characteristics of the pictures can significantly influence the visuospatial cognitive processing capability of the Chinese children. There is a detectable disability for the Chinese dyslexic children in the visuospatial cognitive processing: their saccade amplitude and mean saccade distance are shorter, which may be interpreted as specific for their reading disability.</p>

Effect of Psychological Intervention on Depressive Patients / 中国康复理论与实践

@# Objective To explore the effect of psychological intervention on the rehabilitation of depressive patients.Methods 183 depressive patients were randomly divided into study group (n=93) and control group (n=90). The study group was given systemic psychological intervention additional to routine medicine for 12 weeks and the control group was given only medication. The efficacy was measured by Brief Psychiatric Rating Scale (BPRS), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS).Results There is no significant difference in SDS, SAS and BPRS ratings between two groups before the intervention (P>0.05). The scores of anxiety-depression, lacking-activity, thinking-disturbance, SAS and SDS were significantly lower in the study group than in the control group 12 weeks after the intervention(P<0.05). Conclusion Psychological intervention can positively improve the rehabilitation of depressive patients.