1.Association of coding region single nucleotide polymorphism in cytochrome P4501A1 with susceptibility to childhood acute leukemia
Zeqiao ZOU ; Lijie YUE ; Yanfei REN
Chinese Journal of Applied Clinical Pediatrics 2016;(2):127-131
Objective To investigate the single nucleotide polymorphism(SNP)in the coding region in cyto-chrome P4501 A1 (CYP1A1)gene and to evaluate the contributions of SNPs to acute lymphocytic leukemia(ALL)and acute myeloid leukemia(AML)susceptibility in children.Methods One hundred and twenty -one(male 76,female 45)children with acute leukemia were selected from Department of Hematology in Shenzhen Children′s Hospital,Zuyi Medical College between January 2007 and January 201 4 as the case study group,and the average age was 4.42 years old.Case study group included 1 01 (male 65,female 36,average age 4.38 years old)ALL children (ALL group)and 20(male 1 1 ,female 9,average age 4.66 years old)AML children(AML group).A total of 1 1 6(male 74,female 42) children with respiratory tract infections on health examination during the same period were selected as the control group and the average age was 3.93 years old.SNPs in the coding region in CYP1A1 gene were detected by reverse transcrip-tional(RT)-PCR -denaturing gradient gel elelctrphoresis(DGGE)combined with direct sequencing in the case study group and the control group.Results Only one SNP,A4889G,was screened in the open reading frame (ORF)of CYP1A1 gene in Chinese Han children and the G allele frequency of CYP1A1 gene in the case group,ALL group,AML group and the control group were 31 .4%,32.2%,27.5% and 38.8%.The CYP1A1 A4889G AG and AG +GG geno-type were linked with decreased risk of AML(OR =0.31 ,95%CI:0.1 1 -0.87,P =0.02;OR =0.35,95%CI:0.1 4 -0.93,P =0.03)especially in boys with AML(OR =0.1 2,95%CI:0.03 -0.60,P =0.01 ;OR =0.1 6,95%CI:0.04 -0.65,P =0.01 ),but the CYP1A1 A4889G polymorphism was not associated with the risk of ALL(P >0.05). The CYP1A1 A4889G allele frequency and the distribution of genotypes were significantly different from those reported in America,India,Korea,Brazil and Iran(all P <0.05).Conclusions CYP1A1 A4889G polymorphism may be not as-sociated with susceptibility to ALL,but may decrease the risk of childhood AML especially in boys with AML.In addi-tion,it may exhibit an ethnic difference.
2.Association of CYP1A1 gene polymorphism with adverse reactions of high-does methotrexate in children with acute lymphocytic leukemia
Zeqiao ZOU ; Lijie YUE ; Yanfei REN
The Journal of Practical Medicine 2015;(18):2960-2962
Objective To investigate the association between CYP1A1 gene polymorphism and toxicities related to high-does methotrexate of childhood acute leukemia. Methods The SNPs were detected by reverse transcriptional (RT)-PCR-denaturing gradient gel elelctrphoresis combined with direct sequencing in 51 children with acute leukemia. Toxicities were collected thereby. Results Only one SNP,A4889G, was screened in CYP1A1. A4889G polymorphism was not associated with all the toxicities (P > 0.05). High-risk ALL children were more likely to increase the risk of thrombocytopenia compared with standard-risk ALL (P< 0.05). Conclusions CYP1A1 A4889G polymorphism may be not association with all toxicities after HD-MTX ,but the thrombocytopenia may be relevant to the risk degree of ALL children.
3.β-adrenoceptor activation induces the apoptosis of human mesangial cells
Fanwu KONG ; Yubao LIU ; Lijie LIANG ; Qiushuang LIU ; Yeping REN
Chinese Journal of Nephrology 2015;31(7):516-520
Objective To investigate the effects of β-adrenoceptor (β-AR) activation on the apoptosis in human mesangial cells and it's mechanism.Methods Cultured HMC were used in experiments and were divied into four groups:the control group; β-AR activation (β-AR agonist NE/Pra) group; β-AR inhibitor (Prop) group; antioxidants group.The experiments technology including PCR,confocal scanning microscope,immunofluorescence and Tunel.Results The results of RTPCR and confocal scanning microscope showed that β1-AR and β2-AR were expressed in human HMC.β-AR activation induced reactive oxygen species (ROS) increase in human MCs,the relative levels of ROS were elevated as early as 0.5 h after β-AR activation,and gradually increased and peaked at 4 h on a concentration and time dependent manner.Tunel results demonstrated that β-AR activation induced apoptosis with ROS on a concentration and time dependent manner,β-AR blocking agent-propranolol significantly inhibited β-AR activation induced apoptosis.Antioxidants including vitamin C and NAC could inhibited β-AR activation induced apoptosis (all P < 0.01).Conclusions β-AR is functionally expressed in human mesangial cell,furthermore β-AR activation-induced ROS increase mediate apoptosis.Antioxidants can inhibit β-AR activation induced apoptosis.
4.Correlation between fractional anisotropy values of diffusion tensor imaging and working memory impairment in patients with depression
Lijie REN ; Bingxun LU ; Mingxiang WU ; Manfu HAN ; Jing LI
Chinese Journal of Behavioral Medicine and Brain Science 2010;19(4):325-327
Objective To investigate whether there are correlations between working memory impairmentand fractional anisotropy values and to explore the neuropathology underlying that the patients of depression suffered from memory impairment.Methods Thirty depression patients and 30 healthy controls group-matched by age,educational level were conducted the study.Mean correct reaction time(mRT)was recorded when they performed a One-Back Working Memory Task and fractional anisotropy(FA)values was recorded when they performed the diffusion tensor imaging.Statistics analysis was done respectively for mRT and FA values between two groups.Results Relative to mean correct reaction time((612.45±54.08)ms)of controls,the mean correct reaction time ((720.25±57.02)ms)of patients with depression was much longer(P<0.05)and the patients with depression had a lower FA values in the white matter of both frontal lobe,anterior cingulate gyrus,supramarginal gyrus,splenium of corpus callosum(P<0.05),and the FA values in the white matter of both frontal lobe were significantly negative correlated with mRT(r=-0.604,P<0.05).Conclusion The impairment of white matter region may be one of the neuropathology underlying that the depression patients suffer from memory impairment.
5.The characteristics of cognitive impairment in depression: a combined functional magnetic resonance and event-related potential study
Jun LI ; Lijie REN ; Manfu HAN ; Yuezhi LI ; Zhuqing ZHOU
Chinese Journal of Behavioral Medicine and Brain Science 2013;22(11):985-988
Objective To investigate the characteristics and relative pathogenesis of cognitive impairment in people with depression.Methods 24 people with depression and 24 healthy controls were evaluated respectively with HAMD scale,the WCST test,N-BACK task P300 and fMRI.Results (1) The WCST scores,N-back reaction (MRT),the P300 incubation period in depression group were significantly different from those in control group(P300 wave amplitude(4.12± 1.51) μV vs (6.42± 1.73) μV ; P300 latency(392.02±23.60) ms vs (309.43± 21.39) ms,t=4.922,P<0.01 ; t=12.726,P<0.01).(2) The illness course had positive correlation with Rep(r=0.596,P<0.01) and mRT(r=0.518,P<0.01).The P300 latency had positive correcation with Rpe(r=0.929,P< 0.01) and mRT(r=0.939,P<0.01).(3)Compared with control group,the decreased activation area in patients with depression were as follows:bilateral frontal gyrus,left middle frontal gyrus,inferior frontal gyrus and superior parietal lobule.Conclusion The depressive patients exist cognitive impairment mainly in frontal lobe.The longer with the illness,the wose with the impairment.P300 incubation period is a sensitive indicator of the frontal executive function.
6.Prevalence and risk factors of stroke:findings from a community in Shenzhen, China
Yanxia ZHOU ; Manfu HAN ; Lijie REN ; Feng CHI ; Xiang TANG ; Xia LONG
International Journal of Cerebrovascular Diseases 2016;24(8):716-721
Objective To explore the prevalence and risk factors of stroke in a population over 40 years in a community in Shenzhen, China. Methods The subjects investigated were a population ≥40 years old in this cross-sectional study. Cluster sampling method was used to conduct the unified questionnaires, physical examination, and laboratory examination in the community residents, and then the survey data were used for online entry analysis. Results A total of 5 308 community residents were screened, and 160 experienced stroke. The crude prevalence of stroke was 3 014. 32/100 000. The prevalence of stroke increased with age, and that in males was significantly higher than that in females (3 721. 37/100 000 vs. 2 552. 93/100 000; χ2 = 5. 923, P = 0. 015). There were significant differences in the proportions of males, obvious overweight, hypertension, diabetes mellitus, atrial fibrillation, lack of physical activity, and family history of stroke, as well as age, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and fasting glucose level between the stroke population and the non-stroke population (all P < 0. 05). Multivariate logistic regression analysis showed that hypertension (odds ratio [OR] 1. 737, 95% confidence interval [CI] 1. 161-2. 600; P = 0. 007), diabetes (OR 1. 917, 95% CI 1. 209-3. 040; P = 0. 006), atrial fibrillation (OR 1. 699, 95% CI 1. 113-2. 592; P = 0. 014), family history of stroke (OR 1. 585, 95% CI 1. 126-2. 231; P = 0. 008), advanced age (OR 4. 645, 95% CI 1. 868-11. 551; P = 0. 001), and physical inactivity (OR 4. 921, 95% CI 3. 552-6. 187; P < 0. 001) were the independent risk factors for stroke, and lack of physical activity was an independent protective factor for stroke. The proportion of smoking in males was more than that in females in all ages(all P < 0. 05). The proportions of hypertension (P < 0. 001) and hyperlipidemia (P < 0. 001) were gradually increased with age, and physical exercise was gradually reduced with age (P = 0. 001, except for subjects > 80 years) in both males and females. The proportions of diabetes (P < 0. 001) and atrial fibrillation (P < 0. 001) in males, and obvious overweight (P = 0. 001) in females were gradually increased with age, and the proportion of smoking in males weas gradually reduced with age. The proportions of hypertension (P < 0. 001) and obvious overweight (P < 0. 001) in males were significantly higher than those in females at the age of 40 to 49 years. The proportions of hypertension (P < 0. 001), diabetes (P < 0. 001) and obvious overweight (P < 0. 001) in males were significantly higher than those in females at the age of 50 to 59 years. The proportion of hypertension in males was significantly higher than that in females at the age of 60 to 69 years (P = 0. 039). The proportions of hypertension (P = 0. 016), atrial fibrillation (P = 0. 028) and hyperlipidemia (P = 0. 023) in females were significantly higher than those in males at the age of 70 to 79 years. The proportion of obvious overweight in females was significantly higher than that in males at the age of ≥80 years (P =0. 001). Conclusions The crude prevalence of stroke is higher among the community residents. The the levels of exposure to stroke risk factors including hypertension, diabetes and atrial fibrillation are higher. It may be important to intervene on these risk factors in community residents, especially in elders and those with family history of stroke.
7.Relationship between perfusion mode of carotid plaque in CEUS and ischemic stroke in transient ischemic attack patients
Zhenzhou LI ; Lijie REN ; Yufeng SHAO ; Shenghua CHEN ; Yu QIN ; Xiaoyun GUAN ; Xinyin WU
Chinese Journal of Medical Imaging Technology 2017;33(4):534-538
Objective To evaluate the relationship between the perfusion mode of neovascularization of carotid plaque in CEUS and the ischemic stroke in transient ischemic attack (TIA) patient.Methods A total of 73 TIA patients according to the inclusive criteria were enrolled.All the patients underwent routine carotid ultrasonic examination.And 61 patients with plaque thicker than 2.5 mm in carotid bifurcation underwent CEUS and follow-up for at least 18 months.All the patients were divided into recurrent and non-recurrent groups.Logistic regression analysis were performed to detect the risk factors for incurrence of ischemic stroke or recurrence of TIA in 18 months.Results There were statistical differences between 2 groups in hypertension,diabetes,hyperlipemia,smoking history,family history of stroke,medication compliance,two-dimensional ultrasound and CEUS characteristics (all P<0.05).Multivariate Logistic regression analysis showed that all the factors correlated with the recurrency,from big to small order were the CEUS characteristics of carotid plaque,hypertension,medication compliance,diabetes,two-dimensional ultrasound characteristics of carotid plaque.Conclusion CEUS could evaluate the perfusion mode of neovascularization in carotid plaques.For TIA patients,CEUS could predict the incurrence of ischemic stroke or recurrence of TIA,which can guide TIA patients targeted prophylaxis of them.
8.Association between glutathione S-transferase pi gene polymorphism and adverse reaction of high-dose methotrexate in children with acute lymphoblastic leukemia
Yanfei REN ; Xiuli YUAN ; Lijie YUE ; Zeqiao ZOU ; Cai XIE ; Hui DING ; Ping SONG ; Chang LIU
Chinese Journal of Clinical Oncology 2014;(21):1358-1362
Objective:To investigate the association between glutathione S-transferase pi (GSTP1) gene polymorphism and toxici-ties related to high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:GSTP1 genotypes and allelic frequencies in 51 children with ALL were determined by Nest PCR, denaturing gel gradient electrophoresis (DGGE), and DNA sequencing. HD-MTX adverse reactions were analyzed using the National Cancer Institute Common Toxicity Criteria (NCICTC). Results:We identified three SNPs of GSTP1, including rs1695 (A313G), rs1138272 (G439T), and rs4891 (T555C). The wild types, het-erozygous types, and homozygous types of GSTP1 rs1695/rs4891 polymorphisms were detected in 32 cases (62.7%), 16 cases (31.4%), and 3 cases (5.9%), respectively. GSTP1 rs1695/rs4891 polymorphisms included only one heterozygous type and one homozygous type. The allele frequencies of the three SNPs were 21.6%, 2.9%, and 21.6%. The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 was associated with decrease in the odds of peripheral hemoglobin (OR=0.25, 95%CI=0.06-1.00, P=0.049). The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 in standard and intermediate-risk ALL children was significantly correlated with higher odds of gastrointesti-nal toxicity (OR=0.125, 95%CI=0.02-0.78, P=0.026). Conclusion:GSTP1 rs1695 (A313G)/rs4891 (T555C) gene polymorphism is as-sociated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and inter-mediate-risk ALL children who receive high-dose methotrexate.
9.Correlations between the polymorphisms of serine hydroxymethyl-transferase 1 gene and the adverse reactions of high-dose methotrexate in children with acute lymphoblastic leukemia
Hui DING ; Lijie YUE ; Jie YU ; Cai XIE ; Chunlan YANG ; Yanfei REN ; Chang LIU
Chinese Journal of Clinical Oncology 2014;(3):162-165
Objective:To investigate the correlation between polymorphisms of serine hydroxymethyltransferase1 gene and the adverse reactions of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:A total of 51 patients with ALL were treated with HD-MTX, and clinical manifestations after HD-MTX treatment were evaluated retrospectively. cD-NA was obtained from mRNA. The polymorphisms of SHMT1 gene containing rs1979277, rs3783, rs1979276, and rs12952556 sites were tested by denaturing gradient gel electrophoresis and direct sequencing. Effects of SHMT1 gene polymorphisms on HD-MTX ad-verse reactions were evaluated. Results:Severe adverse reactions in ALL patients treated with HD-MTX appeared to be mainly neutro-penia and hepatoadverse reactions. The frequency distributions of rs3783 (C>G), rs1979276 (C>T), rs12952556 (A>G), and rs1979277 (C>T) were the same. The polymorphisms of rs1979277 showed no correlation with neutropenia (P>0.05) but rs1979277 CT and TT genotypes were correlated with hepatoadverse reactions (CT: OR=0.129, 95% CI: 0.020 to 0.817, P=0.03; TT: OR=0.103, 95% CI:0.017 to 0.620, P=0.013). Conclusion: No correlation was found between the combination of rs1979277, rs3783, rs1979276, rs12952556, and neutropenia, but one or more of these loci may reduce the risk of hepatoadverse reactions.
10.Depression tensor imaging study of depression patients mood processing disorders
Lijie REN ; Jun LI ; Yuezhi LI ; Manfu HAN ; Yufeng SHAO ; Zhuqing ZHOU
Chinese Journal of Behavioral Medicine and Brain Science 2013;22(9):807-809
Objective To investigate the characteristics of the depression during emotional processing.Methods 24 participants with first episode of depression and healthy controls were assessed with HAMD scale,using DTI to dectect values of white matter FA,and using fMRI with pictures of emotional stimuli;thus results related with imagings were produced.The results were statistically analyzed.Results The brain areas indicating FA values deference with statistial significance in depression patients compared with the control ones included:left and right frontal lobe (left frontal lobe depression group 0.324 ± 0.090,control group 0.467 ± 0.072,P < 0.01),corpus callosum knee (depression group 0.614 ±0.146,control group 0.734 ±0.063,P<0.01),anterior cingulate gyrus (depression group 0.222 ±0.035,control group 0.343 ±0.021,P<0.01) ;the fronal FA values in depression grop were negatively correlated with the duration of bilateral frontal white matter (r =-0.555,P < 0.01).The activation of emotional brain regions stimulated by pictures includes frontal cortex-subcortical reticular system,and the hypothalamus and limbic system.There was a significant difference between two groups.Conclusion There may be abnormal emotional processing dystunction in patients with depression.It may be the pathological basis to have frontal white matter fiber tracts broken.