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    Inside front cover
    Expert forum
    Translational medicine pathway: the health care promoted by modern life science discovering
    ZHANG Kan, LI Hui-yi, FANG Yi-fang
    2014, 34 (4):  407. 
    doi: 10.3969/j.issn.1674-8115.2014.04.001

    Abstract ( 998 )   PDF (606KB) ( 1039 )  

    There is the common understanding regarding the limitations of the classic medicine and the optional targets with their pathways in the modern life science age. Based on the characteristics of life science, it is highlighting the cutting edge connections among advanced study, clinic trial and social science for the sprouting of translational medicine as well as the role of pharmaceutical industry. Here, the central player of the ethic value is humanism theory. We are the explorers for the human body secrets while our bodies are the specimen for all the research projects. The translational medicine should be regulated by two guidelines, medical ethic between patient and doctor as well as scientific ethic between researcher and project. As soon as the ethic value meets the development of human society, translational medicine will contribute to all fields of the disease prevention, diagnosis, treatment and rehabilitation finally.

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    Editorial
    Researches on the diagnosis and treatment of bipolar disorder: challenges and opportunities
    FANG Yi-ru, WU Zhi-guo, CHEN Jun
    2014, 34 (4):  413. 
    doi: 10.3969/j.issn.1674-8115.2014.04.002

    Abstract ( 1116 )   PDF (259KB) ( 1111 )  

    Bipolar disorder is a common mental illness with complicated clinical features and variant depressive/manic episode, resulting in under-recognition, misdiagnosis, and inappropriate treatment. Therefore, a series of researches have been carried out to explore its essential features and characteristics. Further more, diagnostic criteria and treatment principals have been modified based on the findings from evidence-based medicine. This paper reviews the current researches on bipolar disorder and their prospects from perspectives such as concepts and diagnoses, neurobiology research progresses, as well as the mood stabilizers treatment.

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    Monographic report
    Effects of DRD2, HTR2A, and HTR2C genes on process of metabolic syndrome induced by clozapine
    ZHANG Yi, ZHANG Chen, CHEN Mei-juan, et al
    2014, 34 (4):  417. 
    doi: 10.3969/j.issn.1674-8115.2014.04.003

    Abstract ( 1083 )   PDF (305KB) ( 1062 )  

    Objective To investigate the effects of dopamine D2 receptor (DRD2), 5-serotonin 2A receptor (HTR2A), and 5-serotonin 2C receptor (HTR2C) genes on the process of metabolic syndrome (MS) induced by clozapine. Methods According to the diagnostic criteria of National Cholesterol Education Program's Adult Treatment Panel Ⅲ (NCEP-ATPⅢ), 199 schizophrenic patients with long-term use of clozapine were divided into MS group and non-MS group. The polymorphisms of DRD2, HTR2A, and HTR2C (rs1800497, rs6311 and rs1414334, respectively) were genotyped by the SNaPshot SNP and the serum levels of fasting plasma glucose (FPG), triglyceride (TG), and high density lipoprotein cholesterol (HDL) were measured. Results The differences of body mass index, levels of waist circumference, FPG, TG, HDL, and blood pressure of two groups were statistically significant (P<0.05). The differences of allele and genotype frequencies of SNPs of two groups were not statistically significant (P>0.05). The differences of FPG levels of patients with different genotypes of rs1800497 were statistically significant (F=3.4, P=0.036) and the FPG levels of patients with T/T genotype were significantly higher than those of patients with C/T genotype (P=0.011). Conclusion The rs1800497 of DRD2 may not be the direct-causing polymorphism of clozapine induced MS. But it may affect the expression of DRD2, cause the abnormal glucose metabolism, and then increase the risk for MS.

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    Analysis of association between polymorphism of Bcl-2 gene promoter and major depressive disorder and its clinical phenotypes
    ZHANG Chen, WU Zhi-guo, HONG Wu, et al
    2014, 34 (4):  422. 
    doi: 10.3969/j.issn.1674-8115.2014.04.004

    Abstract ( 857 )   PDF (285KB) ( 913 )  

    Objective To investigate the genetic association between the polymorphism of rs2279115 of Bcl-2 gene promoter and the major depressive disorder (MDD) and its clinical phenotypes among Chinese Han population. Methods Totally 701 MDD patients (the MDD group) who visited the Division of Mood Disorders of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine from January, 2006 to December, 2012 and 725 healthy control subjects (the control group) were chosen for the study. The clinical phenotypes of patients were determined by the 17 items of Hamilton Depression Rating Scale (HAMD). The peripheral blood samples were collected and the DNA was extracted. Rs2279115 was then genotyped by the TaqMan SNP genotyping assay. Results The differences of frequencies of genotypes and alleles of rs2279115 between the MDD group and control group were not statistically significant (P>0.05). The differences of scores of HAMD, depressive emotion, and general symptom among polymorphous genotypes of rs2279115 were statistically significant (P<0.05). The scores of HAMD, depressive emotion, and general symptom of MDD patients with C/C genotype were significantly higher than those of MDD patients with C/A or A/A genotype. Conclusion The rs2279115 of Bcl-2 gene promoter may be relevant to the clinical symptoms of MDD.

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    Relationship between dopamine receptor D4 exon Ⅲ polymorphism and the Gilles de la Tourette syndrome comorbid with depression
    JI Wei-dong, LI Ning, ZHENG Hong, et al
    2014, 34 (4):  426. 
    doi: 10.3969/j.issn.1674-8115.2014.04.005

    Abstract ( 1033 )   PDF (296KB) ( 1042 )  

    Objective To investigate the relationship between the polymorphism of repeatable sequence of DRD4 exonⅢ 48 bp gene and depressive symptoms in children with Gilles de la Tourette syndrome (TS). Methods A total of 112 children who were diagnosed as TS according to the criteria of the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (the TS group) and 71 healthy children (the control group) were selected. The polymorphous points of DRD4 gene were genotyped by the amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) genotyping assay method and the depressive levels of children with TS were measured by the children's depression inventory (CDI). Results Among 112 children with TS, 29 (25.9%) were diagnosed with depression. The differences of genotype frequency and allele frequency of DRD4 exonⅢ 48 bp VNTR among the TS group, comorbid depression group, and control group were not statistically significant (P>0.05). The differences of CDI scores and factor scores between 61 children who carried long repeat allele group and 51 children who carried short repeat allele group were not statistically significant (P>0.05). Conclusion The DRD4 exonⅢ 48 bp VNTR may not correlate to the TS comorbid depression.

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    Comparison of the clinical features of patients with early-onset and late-onset treatment-resistant depression
    LIAO Li-wei, WU Zhi-guo, CAO Lan, et al
    2014, 34 (4):  431. 
    doi: 10.3969/j.issn.1674-8115.2014.04.006

    Abstract ( 944 )   PDF (258KB) ( 998 )  
    Objective To compare the clinical features of patients with early-onset and late-onset treatment-resistant depression. Methods Three hundred and seventy adult patients with treatment-resistant depression were divided into the early-onset group (n=193) and late-onset group (n=177) by the median method. The clinical features of two groups were compared and analyzed. Results Compared to the late-onset group, the proportions of male, introverts, and patients who completed nine-year voluntary education of early-onset group were higher (P<0.001) and the current episodes were longer, i.e. (17.32±25.94) months and (12.47±18.42) months, respectively (P=0.015). Compared to the early-onset group, the proportion of married patients, Hamilton depressive scale-17 items (HAMD-17) scores of depression level, and factor sleep disorder scores of late-onset group were all significantly increased (P<0.001), and the proportion of physical comorbidities was much higher (P=0.008). Conclusion The clinical features of patients with early-onset and late-onset treatment-resistant depression are different. The differences may be relevant to the potential pathophysiological mechanisms.
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    Study on evaluation of clinical guidelines of bipolar disorder
    WAN Yu-mei, LI Wei, HU Qiang, et al
    2014, 34 (4):  435. 
    doi: 10.3969/j.issn.1674-8115.2014.04.007

    Abstract ( 962 )   PDF (397KB) ( 992 )  

    Objective To evaluate the quality of methodologies of clinical guidelines on the bipolar disorder by using the Appraisal of Guidelines for Research and Evaluation (AGREEⅡ). Methods Clinical guidelines from home and abroad that met the study criteria were retrieved from the Chinese National Knowledge Infrastructure, Chongqing VIP database for Chinese Technical Periodicals, WANFANG DATA, Chinese Biological Medical Literature Database, PubMed, OVID, BMJ Best Practice, Dynamed, ISI Web of Knowledge, National Guideline Clearinghouse (NGC), Guidelines International Network (G-I-N), Scottish Intercollegiate Guidelines Network (SIGN), and other related websites. Search words were bipolar disorder and clinical guideline. The quality of methodologies of these clinical guidelines was evaluated based on the AGREEⅡ. Results Seventeen clinical guidelines were selected. The overall median domain scores of AGREEⅡ showed that the bestperforming domains were clarity of presentation (83%) and scope and purpose (69%), and followed by rigour of development (40%) and stakeholder involvement (31%). Editorial independence (25%) and applicability (15%) got the lowest scores. The scores of rigour of development, clarity of presentation, applicability, stakeholder involvement and scope and purpose of the evidence-based guidelines were higher than those of the expert consensus guidelines. The score of editorial independence of Chinese guideline on prevention and treatment of bipolar disorder was zero and its scores were lower than the overall median scores of other fourteen evidence-based guidelines. Conclusion The overall quality of methodologies of evaluated clinical guidelines on bipolar disorder cannot meet the criteria of AGREE Ⅱ. AGREE Ⅱ is recommended to be used to develop and update the clinical guidelines.

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    Investigation and influence factors of anxiety of junior high school students in Jiading District of Shanghai
    CHEN Xiang-chun, WU Yan, BAN Chun-xia, et al
    2014, 34 (4):  442. 
    doi: 10.3969/j.issn.1674-8115.2014.04.008

    Abstract ( 794 )   PDF (238KB) ( 1104 )  

    Objective To investigate the prevalence and influence factors of anxiety of the junior high school students in Jiading District of Shanghai. Methods The Screen for Child Anxiety Related Emotional Disorders (SCARED) was used to evaluate the anxiety status of 2 011 students from 6 junior high schools in Jiading District of Shanghai. Results The total detection rate of anxiety was 38.4%. The differences of detection rates of students with different ages were statistically significant (P<0.001). The detection rate of 14 years old students was the highest. The differences of detection rates between local students and non-local students were statistically significant (P<0.05). The detection rate of nonlocal students was higher. The prevalence of anxiety disorder was relevant to junior grade, girls, and parents with lower education levels (P<0.05). Conclusion The prevalence of anxiety disorder in the junior middle school students in Jiading District of Shanghai is high and the detection rate of non-local students is higher than that of local students. The risk factors may be junior grade, girls, and parents with lower education levels.

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    Survival analysis of patients with first diagnosed bipolar disorder
    CHEN Si-lu, JI Wei-dong, FANG Yi-ru, et al
    2014, 34 (4):  446. 
    doi: 10.3969/j.issn.1674-8115.2014.04.009

    Abstract ( 998 )   PDF (240KB) ( 849 )  

    Objective To analyze the survival and relevant influence factors of patients with first diagnosed bipolar disorder and being treated by medicines. Methods Clinical data of 785 patients with first diagnosed bipolar disorder were collected. The survival curves were plotted by the Kaplan-Meier method. The survival and influence factors were statistically analyzed by the Cox proportional hazard model for patients after being treated for one year. Results Among 785 patients, the cumulative survival rates of 2.5, 5, 7.5, 10, and 12.5 months after treatment were 0.98, 0.96, 0.95, 0.94, and 0.65, respectively. By the end of follow-up, 82 patients died and the mortality rate was 10.4%. The mortality rate during twelve months after first treatment was 4.3%. Multivariate Cox regression analysis showed that the somatic diseases and combined antipsychotic drug treatment programs were relevant to the survival time of patients. Conclusion For patients with first diagnosed bipolar disorder, early combined antipsychotic drug treatments can prolong the survival time of patients and increase the mortality rate. Somatic diseases are dangerous factors that influence the survival of patients.

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    Interpreting the complexity of major depression through the concept of anxious depression
    WU Zhi-guo, WU Yan, FANG Yi-ru
    2014, 34 (4):  450. 
    doi: 10.3969/j.issn.1674-8115.2014.04.010

    Abstract ( 1123 )   PDF (330KB) ( 1201 )  

    Major depression is a kind of extremely complex illness. Currently, many clinical subtypes of major depression have been developed in order to accurately interpret the complexity of this illness. Among which the anxious depression has received more and more attention. This paper will interpret the complexity of major depression through the review of recent literatures focusing on depression with concurrent anxiety and dimensional defined anxious depression.

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    Research progresses of major depressive disorder with painful physical symptoms
    LI Ning-ning, WU Zhi-guo, FANG Yi-ru
    2014, 34 (4):  455. 
    doi: 10.3969/j.issn.1674-8115.2014.04.011

    Abstract ( 1178 )   PDF (245KB) ( 1056 )  
    Major depressive disorder (MDD) is a kind of extremely complex mental illness. The concurrent pain or other physical symptoms are chief complaints of patients with MDD and may lead to misdiagnosis and treatment delay. So it is clinically essential for the treatment of MDD with concurrent pain symptoms to thoroughly explore the features and related clinical indexes. This paper reviews the research progresses on MDD with pain symptoms.
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    Advances of  role of glutamate in anxiety disorder
    LI Meng-yao, WU Yan, DU Ya-song
    2014, 34 (4):  459. 
    doi: 10.3969/j.issn.1674-8115.2014.04.012

    Abstract ( 1127 )   PDF (307KB) ( 1073 )  
    The anxiety disorder is one of the most common mental disorders in clinical practice. The role of glutamate neurotransmitters in the development and treatment of anxiety disorder is being increasingly studied in recent years. This paper reviews the progresses of the mechanism of glutamine on the anxiety disorder and the clinical researches on medication related to the glutamine pathway.
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    Original article (Basic research)
    Effects of hypoxia induced by CoCl2 on expression of adiponectin in 3T3-L1 adipocytes
    LIN Ning, ZHANG Zhu-hua, LI Xiao-yong, et al
    2014, 34 (4):  464. 
    doi: 10.3969/j.issn.1674-8115.2014.04.013

    Abstract ( 1097 )   PDF (547KB) ( 1011 )  
    Objective To investigate the effects of hypoxia induced by CoCl2 on the expression of adiponectin (ADPN) in mouse 3T3-L1 adipocytes. Methods 3T3-L1 preadipocytes were cultured and differentiated to matured adipocytes in vitro. Cell differentiation and lipid accumulation were determined by oil red O staining. CoCl2 was used as a chemical hypoxia-inducible reagent to simulate hypoxic microenvironment. The expressions of hypoxia-inducible factor-1α (HIF-1α) and ADPN mRNA were detected by Real-Time PCR. The protein expressions of HIF-1α were determined by Western blotting and the secretion levels of ADPN protein in cell culture supernatant were detected by ELISA. Results Under the hypoxia condition induced by CoCl2, the expression levels of HIF-1α mRNA and protein in 3T3-L1 adipocytes were significantly increased, while the expressions of ADPN mRNA in 3T3-L1 adipocytes and the secretion levels of ADPN protein in cell culture supernatant were significantly decreased. The expression levels of HIF-1α mRNA and ADPN mRNA had significantly negative correlation (r=-0.854, P<0.001). Conclusion The hypoxia induced by CoCl2 can decrease the expression of ADPN in 3T3-L1 adipocytes. This effect may be relevant to the metabolic function impairment of adipose cells and insulin resistance.
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    Effects of expressions of C-type lectin receptor in surface of dendritic cells on biological behaviors of extravillous cyototrophoblasts
    XUE Zhuo-wei, XIONG Miao, JIANG Rong-zhen, et al
    2014, 34 (4):  469. 
    doi: 10.3969/j.issn.1674-8115.2014.04.014

    Abstract ( 1121 )   PDF (493KB) ( 1095 )  
    Objective To use gene cloning techniques to construct the gene overexpression/siRNA lentiviral vector of C-type lectin receptor (CLR) and observe the effects of the overexpressed/low expressed CLR, which are on surface of placenta originated dendritic cells, on the invasion, adhesion ability, and apoptosis of extravillous cytotrophoblasts (EVCT). Methods The CLR overexpressed/low expressed dendritic cells were acquired by plasmid transfection and RNA interference. The primary human EVCT were isolated, cultured, identified and then co-cultured with CLR overexpressed/low expressed dendritic cells (i.e. the overexpressing group and low expressing group). The effects of co-culture on invasion, adhesion ability, and apoptosis of EVCT were examined by the in vitro invasion assay, adhesion experiment, and AnnexinV/PI double staining. The EVCT not being co-cultured were used as the control group. Results The differences of invasiveness of EVCT between the overexpressing group and the control group were not statistically significant (P>0.05). The invasiveness of EVCT of the low expressing group was distinctly weaker than that of the control group (P<0.01). The value of adhesive ability of the overexpressing group was (94.2±2.3)% and the value of adhesive ability of the control group and the low expressing group was only (52.8±1.5)%. The adhesive ability of EVCT of the low expressing group was significantly lower (P<0.01). The apoptotic rates of the overexpressing group, low expressing group, and control group were (3.9±0.8)%, (8.2±1.4)%, and (1.1±0.3)%, respectively. The apoptotic rate of the low expressing group was significantly higher than that of the control group (P<0.01). Conclusion To inhibit the expressing of CLR on surface of dendritic cells can significantly decrease the invasiveness and adhesion ability of EVCT and significantly increase the apoptotic rate. This indicates that the abnormal expression of CLR may be one of the important mechanisms of the immune injury of EVCT and the onset of preeclampsia.
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    Effects of preconditioning with cinepazide maleate on MAPK signal transduction pathway of rats with cerebral ischemia
    PU Zheng, GAN Jing, WANG Xiao-rong, et al
    2014, 34 (4):  475. 
    doi: 10.3969/j.issn.1674-8115.2014.04.015

    Abstract ( 761 )   PDF (422KB) ( 1009 )  
    Objective To observe the effects of preconditioning with cinepazide maleate on the expressions of extracellular signal regulated kinases (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) of rats with cerebral ischemia and to explore the neuroprotective function of cinepazide maleate. Methods SD rats were randomly divided into the cinepazide maleate injection preconditioning operation group (treatment-operation group), normal saline injection preconditioning operation group (control-operation group), and cinepazide maleate injection preconditioning non-operation group (treatment-non-operation group). Each group had 30 rats and was preconditioned for 5 days. The cerebral ischemia models were established by occluding the left middle cerebral artery of rats in two operation groups through a modified suture method. At 8 h, 24 h, and 72 h after operations, brain tissues were taken out and their left side (ischemic side) and the corresponding right side were excised. The expressions and phosphorylation levels (the expressions of p-ERK1/2 and p-p38 MAPK) of ERK1/2 and p38 MAPK in both sides of brain tissues at each time point were detected by the Western blotting. Results The differences of relative expressions of total proteins of ERK1/2 and p38 MAPK in rat brain tissues from each group were not statistically significant (P>0.05). Compared to the treatment-non-operation group, the relative expressions of p-ERK1/2 protein in left side (operation side) of brain tissues of rats in the treatment-operation group and control-operation group at 8 h after operations were significantly up-regulated and were significantly down-regulated at 24 h and 72 h after operations. The differences were statistically significant (P<0.05). Also compared to the treatment-non-operation group, the relative expressions of p-p38 MAPK protein in left side (operation side) of brain tissues of rats in the treatment-operation group and control-operation group at 8 h, 24 h, and 72 h after operations were significantly up-regulated and the expressions of p-p38 MAPK protein of control-operation group was statistically higher than that of the treatment-operation group. The differences were statistically significant (P<0.05). Conclusion Cinepazide maleate may have protective effects at the early stage of cerebral ischemia.
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    Mechanism of effects of rapamycin on growth inhibition and inducing apoptosis of human neuroblastoma cell line
    CHEN Sheng, GU Shuo, XU Min, et al
    2014, 34 (4):  481. 
    doi: 10.3969/j.issn.1674-8115.2014.04.016

    Abstract ( 1040 )   PDF (555KB) ( 1090 )  
    Objective To investigate the effects of rapamycin on growth inhibition and inducing apoptosis of human neuroblastoma cell line SH-SY5Y and the target signaling pathway of phosphatidylinositol-3-kinase/protein kinase B/the mammalian target of rapamycin (PI3K/Akt/mTOR). Methods The rapamycin intervention group contained SH-SY5Y cells treated by the rapamycin of different concentrations (10, 15, 20 μmol/L). The negative control group contained SH-SY5Y cells by adding the same volumes of DMSO. The blank control group was also established. The CCK-8 assay, flow cytometry assay, and annexin Ⅴ-FITC/PI double staining were used to determine cell proliferation rate, cell cycle, and apoptosis rate of SH-SY5Y cells, respectively. Western blotting was performed to determine expressions and changes of phosphorylation level of cleaved caspase-3 and upstream and downstream molecules of signaling pathway of PI3K/Akt/mTOR, including PI3Kp85, Akt, mTOR, and 4E-BP1. Results Compared to the negative control group and blank control group, the cell growth rate of rapamycin intervention group decreased significantly (P<0.05 or P<0.01). Cell cycle analysis further showed that rapamycin could arrest the cell cycle at G0/G1 phase (P<0.05). Early and late apoptosis in SH-SY5Y cells treated by rapamycin were evident through annexin Ⅴ-FITC/PI staining assay (P<0.01). The results of Western blotting showed that the expression level of cleaved caspase-3 of rapamycin intervention group was higher than that of the negative control group and blank control group; the activities of upstream and downstream molecules of signaling pathway of PI3K/Akt/mTOR were inhibited; and the phosphorylation levels of PI3K, Akt, mTOR, and 4E-BP1 were significantly decreased. Conclusion The rapamycin can inhibit the cell growth and induce the apoptosis of human neuroblastoma cell line SH-SY5Y. The mechanism may be relevant to the suppression of signaling pathway of PI3K/Akt/mTOR.
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    Effects of dexmedetomidine on function of intestinal mucosal barrier of rats with ischemia-reperfusion injury
    ZHANG Ying, ZHONG Wen-hui, WANG Ai-zhong
    2014, 34 (4):  487. 
    doi: 10.3969/j.issn.1674-8115.2014.04.017

    Abstract ( 908 )   PDF (507KB) ( 1227 )  
    Objective To observe the effects and to discuss the mechanism of dexmedetomidine on the intestinal fatty acid binding protein (I-FABP) and inflammatory factors of rats with intestinal ischemia-reperfusion injury. Methods The intestinal ischemia reperfusion injury model of rats was established and then rats were randomly divided into the sham operation group, ischemia-reperfusion group, and dexmedetomidine group. The aortic blood of rats was extracted at the 2 h and 6 h after ischemia-reperfusion. The plasma I-FABP levels were measured by ELISA. By the end of experiments, the contents of IL-6 and IL-10 in intestinal tissues were measured by ELISA. The intestinal tissues were stained by the HE and their injury severity was scored by the methods of Chiu's six levels. Results The plasma I-FABP levels of the ischemia-reperfusion group and dexmedetomidine group at 2 h and 6 h after reperfusion were significantly higher than those of the sham operation group. The differences were statistically significant (P<0.05). Compared to the ischemia-reperfusion group, the plasma I-FABP levels of the dexmedetomidine group were significantly decreased. The differences were statistically significant (P<0.05). The contents of IL-6 and IL-10 in intestinal tissues of the ischemia-reperfusion group and dexmedetomidine group were significantly higher than the sham operation group. The differences were statistically significant (P<0.05). Compared to the ischemia-reperfusion group, the contents of IL-6 in intestinal tissues of the dexmedetomidine group were lower, while the contents of IL-10 were higher. The differences were statistically significant (P<0.05). The Chiu's score of the dexmedetomidine group was significantly lower than that of the ischemia-reperfusion group but higher than that of the sham operation group. The differences were statistically significant (P<0.05). Conclusion Dexmedetomidine can effectively reduce the production of inflammatory factor after intestinal ischemia reperfusion, decrease the content of plasma I-FABP, and protect the intestinal functions.
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    Study on proteomic profiling of hippocampus tissues of spontaneously hypertensive rats after propofol anesthesia
    HU Jiang, WEN Da-xiang, HANG Yan-nan
    2014, 34 (4):  491. 
    doi: 10.3969/j.issn.1674-8115.2014.04.018

    Abstract ( 849 )   PDF (412KB) ( 1066 )  
    Objective To investigate the effects of propofol anesthesia on the expressions of hippocampus protein and it's relationship with the cognitive function of spontaneously hypertensive rats. Methods Forty spontaneously hypertensive rats were randomly divided into the experiment group (n=20) and control group (n=20). The rats of experiment group were given 100 mg/kg of propofol by peritoneal injection for anesthetic induction and the anesthesia was maintained for 3 h by administering half dose of inductive propofol after 1 h and 2 h. The control group was treated by saline with the same procedure and volume as to propofol injection. Five rats in each group were randomly chosen and decapitated at 3 h, 24 h, 72 h, and on 7 d after anesthesia. Hippocampus tissues were immediately removed to an ice-board and subjected to global protein expression profiling based on two-dimensional gel electrophoresis. Spots expressed with more than two-fold changes were cut out for analysis by the MALDI-TOF-MS. The major functions and involved biological processes of differential proteins were analyzed by database retrievals. Results Eighty-four differentially expressed proteins were detected, among which sixty eight proteins were successfully identified by the MALDI-TOF-MS and 47 proteins were determined by retrievals of protein databases after duplicating ones were removed. Most proteins were low expressed and maintained till the 7 d after anesthesia. Many biological processes (involving the energy metabolism, mitochondrial function, protein folding, and vesicle trafficking, etc.) were affected. Conclusion The influence of propofol anesthesia results in multi-dimensional and dynamic changes of hippocampusin of spontaneously hypertensive rats. Differential expressions of some proteins may involve the molecular mechanism of impairing the cognitive function, but its actual effects need further investigation.
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    Protective effect of transfection of angiotensin converting enzyme 2 gene on atherosclerotic vascular endothelial cells
    CHEN Xu, ZHU Li, HAO Qing-qing, et al
    2014, 34 (4):  496. 
    doi: 10.3969/j.issn.1674-8115.2014.04.019

    Abstract ( 780 )   PDF (530KB) ( 1126 )  
    Objective To explain the protection effect and mechanism of gene transfection of angiotensin converting enzyme 2 (ACE2) towards endothelial cells by observing the effects of gene transfection of ACE2 on vascular endothelial cells of model rabbits with atherosclerosis. Methods The atherosclerosis model of rabbit was established by balloon injuries of endothelial cells and atherogenic diet. Sixteen New Zealand rabbits were randomly divided into the Ad-ACE2 group (transfected by the recombinant adenovirus carrying the ACE2 gene) and Ad-EGFP group (transfected by the recombinant adenovirus without carrying the ACE2 gene). Each group consisted of 8 rabbits. The rabbits of two groups received abdominal aortic injections of ACE2 recombinant adenovirus (2.5×109 pfu/mL) and Ad-EGFP, respectively. After one month, all rabbits were sacrificed and specimens of plaques from abdominal aorta segments were prepared. The protein expressions of ACE2 in atherosclerotic plaques were detected by the Western blotting. The expressions of intercellular adhesion molecule-1 (ICAM-1) and P-selectin protein were evaluated by the immunohistochemical staining. The semi-quantitative analysis was carried out by the oil red O staining. Results The results showed that the expressions of ACE2 protein of the Ad-ACE2 group were significantly higher than that of the Ad-EGFP group (P<0.05). The positive expression rates of ICAM-1 and P-selectin protein in plaques of the Ad-ACE2 group were significantly lower than those of the Ad-EGFP group [(16.95±3.09)% vs (24.81±4.78)% and (16.22±2.45)% vs (23.46±3.28)%, respectively]. The differences between two groups were statistically significant (P<0.01). The lipid contents in plaques of the Ad-ACE2 group (41.77±3.17)% were significantly lower than those of the Ad-EGFP group (59.55±1.53)%. The differences between two groups were statistically significant (P<0.05). Conclusion ACE2 gene transfection can protect the endothelial cells of rabbits and inhibit the development of atherosclerosis by down-regulating the expressions of ICAM-1 and P-selectin protein.
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    Effects of miR-20b on regulation of expression of vascular endothelial growth factor in RAW264.7 cells of mice
    SONG Chuan-wang, TAO Xiang-nan, TANG Jie, et al
    2014, 34 (4):  501. 
    doi: 10.3969/j.issn.1674-8115.2014.04.020

    Abstract ( 817 )   PDF (489KB) ( 1123 )  

    Objective To explore the effects of miR-20b on the expression of vascular endothelial growth factor (VEGF) in RAW264.7 cells of rats. Methods RAW264.7 cells of mice were stimulated by different concentrations (1, 10, 50, 100, and 200 ng/mL) of TNF-α for 24 h and the amount of VEGF in the supernatant was detected by the ELISA. The miR-20b and VEGF mRNA expressions were detected by the Real-Time PCR for RAW264.7 cells stimulated by TNF-α (50 ng/mL) for 6 h. The Pictar algorithm was used to predict whether VEGF was a regulating target of miR-20b. MiR-20b mimics and its control were transfected into RAW264.7 cells by Lipofectamine 2000. ELISA was used to detect the amount of VEGF in the supernatant after the transfected RAW264.7 cells were stimulated by TNF-α (100 ng/mL) for 24 h. Results TNF-α induced the RAW264.7 cells to secret VEGF and 50-100 ng/mL TNF-α was the most suitable concentration for stimulation. After RAW264.7 cells were stimulated by TNF-α (50 ng/mL) for 6 h, the expression of VEGF was elevated to (1.60±0.85) times of that of the control group, while the expression of miR-20b was decreased to (0.55±0.33) times of that of the control group. The Pictar algorithm showed that the VEGF 3′-UTR contained the complementary sequences ‘GCACUUU’ of miR-20b seed region ‘AAAGUGC’. The increased expression of VEGF protein was completely inhibited after TNF-α-stimulated RAW264.7 cells were transfected with miR-20b mimics (P<0.01), while for the control group, transfected with miR-20b mimics had no significant effect on the production of VEGF (P>0.05). Conclusion MiR-20b can negatively regulate the expression of VEGF in RAW264.7 cells of mice.

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    Original article (Clinical research)
    Application value of sinus heart rate turbulence and heart rate variability on prognosis evaluation of patients with acute coronary syndrome
    YUAN Min-jie, LI Jing-bo,WEI Meng, et al
    2014, 34 (4):  507. 
    doi: 10.3969/j.issn.1674-8115.2014.04.021

    Abstract ( 916 )   PDF (446KB) ( 1108 )  

    Objective To observe the major adverse cardiac events (MACE) and to explore the predictive effects of sinus heart rate turbulence (HRT) and heart rate variability (HRV) on the prognosis of patients with acute coronary syndrome (ACS) through the perioperative detection and follow-up. Methods The prospective method was used for 167 patients who were diagnosed with ACS and underwent coronary angiography (CAG) and percutaneous coronary intervention (PCI) treatment. Delmar dynamic ECG detection system (USA) was used to give 24 h dynamic electrocardiogram examination for each patient within 2-4 weeks of onset. The HRT was evaluated by the turbulence onset (TO) and turbulence slope (TS) and the HRV was evaluated by the standard deviation of consecutive 24 h normal RR interval (SDNN). The followup was continued for at least 5 months and the occurrence of MACE was observed. Results There were 51 cases of abnormal HRT, among which 7 were with MACE (13.73%). Among 59 cases of normal HRT, 7 cases were with MACE (11.85%). The differences of the occurrence rate of MACE between patients with abnormal HRT and normal HRT were not statistically significant (P>0.05). The sensitivity, specificity, and accuracy of prediction of MACE for patients with ACS by the HRT were 50.0%, 54.2%, and 53.6%, respectively. The positive value and negative value of prediction of MACE for patients with ACS by the HRV were 9.1% and 92.4%, respectively. Decreased SDNN was relevant to the occurrence of MACE (P<0.05). Conclusion The perioperative 24-hour dynamic electrocardiogram examination is critical. Reduced HRV is important for predicting the prognosis of patients with ACS, while the predictive value of HRT is limited.

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    Distribution of EGFR gene mutations of early stage non-small cell lung cancer
    LI Yong, LI Zi-ming, LU Shun
    2014, 34 (4):  511. 
    doi: 10.3969/j.issn.1674-8115.2014.04.022

    Abstract ( 958 )   PDF (297KB) ( 912 )  

    Objective To explore the distribution of EGFR mutations in the early stage of non-small cell lung cancer (NSCLC). Methods Specimens from primary tumors of patients with NSCLC treated by radical surgeries in Shanghai Chest Hospital from June 1, 2003 to June 1, 2011 were collected. The EGFR mutations were detected by the PCR amplification and direct sequencing methods. The clinical pathological features between patients with EFGR sensitive mutations and patients with non EGFR sensitive mutations were compared by the chi-squared test. The correlation between EGFR sensitive mutations and clinical pathological features was analyzed by the logistic regression method. Results Among 165 patients with NSCLC, 93 cases were wild-type EGFR (56.36%,93/165); 72 cases were EGFR mutations (43.64%,72/165); and 56 cases (33.94%,56/165) were sensitive mutations (33 cases of 19del and 23 cases of 21L858R point mutation). The sensitive mutations accounted for 77.78% of all mutations (56/72). The single factor analysis showed that EGFR sensitive mutations were more frequently found in patients with adenocarcinoma, no smoking, positive EGFR fluorescent in situ hybridization (FISH) amplification, and the diameter of primary tumor less than 5 cm. Logistic regression analysis showed that the pathological type and size of primary tumor were independent prediction factors of sensitive mutations for patients with early stage NSCLC. The probability of mutations of patients with adenocarcinoma and lesion diameter less than 5cm was 4.435 times (95%CI 1.209-16.273, P=0.025) and 4.343 times (95%CI 1.393-13.540, P=0.011) than those of patients with non-adenocarcinoma or lesion diameter greater than or equal to 5 cm, respectively. Conclusion Among the patients with early stage NSCLC, the probability of sensitive mutations of those who with adenocarcinoma, no smoking, primary lesion diameter less than 5 cm, and positive EGFR FISH amplification is higher. The pathological type and size of primary tumor are independent prediction factors of sensitive mutations for patients with early stage NSCLC.

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    Analysis of therapeutic effects of simultaneous resection and staged resection of bilateral adrenal pheochromocytomas
    HUANG Bao-xing, SUN Fu-kang, HUANG Xin, et al
    2014, 34 (4):  515. 
    doi: 10.3969/j.issn.1674-8115.2014.04.023

    Abstract ( 800 )   PDF (324KB) ( 954 )  

    Objective To compare the therapeutic effects of simultaneous resection and staged resection of bilateral adrenal pheochromocytomas. Methods Clinical data of 43 patients whose bilateral adrenal pheochromocytomas were surgically treated was analyzed retrospectively. Patients were divided into the simultaneous resection group (bilateral adrenal pheochromocytomas were simultaneously resected, n=23) and staged resection group (bilateral adrenal pheochromocytomas were resected in stages, n=20) according to different surgical procedures. Baseline characteristics and testing results of perioperative and postoperative indexes of the two groups were compared. Results All patients of the simultaneous resection group underwent open surgeries. For the staged resection group, 16 patients underwent open surgeries for both pheochromocytomas; 2 patients underwent open surgeries for one pheochromocytoma and laparoscopic operations for the other pheochromocytoma; and 2 patients underwent laparoscopic operations for both pheochromocytomas. The operative time, volumes of blood loss, incidences of intraoperative significant fluctuation of blood pressure, incidences of postoperative transient adrenocortical insufficiency, postoperative hospitalization time, left tumor sizes, and right tumor sizes of patients undergone open surgeries of the simultaneous resection group and staged resection group were 3.66 h and 2.11 h (P<0.05), 1 680 mL and 276.92 mL (P<0.05), 52.17% and 18.67% (P<0.05), 82.61% and 44.44% (P<0.05), 12.07 d and 10.41 d (P>0.05), 4.32 cm and 5.64 cm (P>0.05), 5.10 cm and 4.01 cm (P>0.05), respectively. The average follow-up time of two groups was 9.3 years (from 4 months to 27 years). The recurrences of the simultaneous resection group and staged resection group were 26.1% (6 cases) and 15% (3 cases). Conclusion Compared to the simultaneous resection, the staged resection of bilateral adrenal pheochromocytomas shows higher perioperative safety, shorter postoperative convalescence, less complications, and lower recurrence and may be an ideal surgical procedure for patients with bilateral adrenal pheochromocytomas, especially for patients with high risk.

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    Study on prenatal diagnosis of high-risk fetuses with chronic granulomatous disease
    TIAN Wen, JIANG Li-ping, SHU Lan, et al
    2014, 34 (4):  520. 
    doi: 10.3969/j.issn.1674-8115.2014.04.024

    Abstract ( 1043 )   PDF (638KB) ( 958 )  

    Objective To investigate the value of gene analysis of amniotic fluid exfoliated cells and the neutrophil respiratory burst assay of embryo cord blood in prenatal diagnosis of high-risk fetuses with chronic granulomatous disease (CGD). Methods Six patients with CGD who were diagnosed by the Children's Hospital of Chongqing Medical University through the gene analysis were selected, including five cases of X-linked CGD (X-CGD) and one case of autosomal recessive CGD (AR-CGD). Eight samples of amniotic fluid were obtained by the amniocentesis for eight high-risk fetuses in six pedigrees. The RNA and DNA of amniotic fluid exfoliated cells were extracted. CYBB and CYBA genes were amplified by the polymerase chain reaction (PCR) and the sequencing was performed on the PCR products. Embryo blood samples were collected from two high-risk fetuses by percutaneous umbilical blood sampling. Neutrophil respiratory burst assays were conducted by the flow cytometry and the analysis of above genes was performed. Results The analytical results of CYBB and CYBA genes of amniotic fluid exfoliated cells showed that among seven cases of five X-CGD pedigrees, one female fetus and one male fetus were normal; mutated genes carried by two female fetuses were unidentified; two male fetuses were X-CGD patients; one male fetus was suspicious X-CGD patient; and one female fetus of one AR-CGD pedigree was suspicious AR-CGD patient. The respiratory burst function of neutrophil in embryo cord blood samples of the two suspicious CGD fetuses was very low. The genes analysis of above two embryo cord blood samples identified one X-CGD male fetus and one AR-CGD female fetus. Four healthy fetuses were delivered smoothly and four CGD fetuses were artificially aborted. Conclusion The gene analysis of amniotic fluid exfoliated cells combined with the respiratory burst assay of neutrophil in embryo cord blood can provide reliable prenatal diagnosis for high-risk fetuses with CGD.

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    Meta-analysis of Asn680Ser polymorphism of follicle stimulating hormone receptor and susceptibility of polycystic ovary syndrome
    QIU Lei, ZENG Yu, LIU Jing, et al
    2014, 34 (4):  527. 
    doi: 10.3969/j.issn.1674-8115.2014.04.025

    Abstract ( 889 )   PDF (466KB) ( 988 )  

    Objective To evaluate the correlation of the single-nuleotide polymorphism (Asn680Ser polymorphism) of follicle-stimulating hormone receptor (FSHR) and the susceptibility of polycystic ovarian syndrome (PCOS) by the meta-analysis. Methods Databases including the Pubmed, Ovid, EMBASE, CBM, and CNKI were searched to collect the case-control studies on the correlation of the Asn680Ser polymorphisms of FSHR gene and PCOS susceptibility. Records before January, 2013 were retrieved. Records were screened independently by two reviewers according to the inclusion and exclusion criteria. Data were extracted and the quality was evaluated. Then the data were analyzed by the meta-analysis using the Stata 11.0 software and the Begg's funnel plot was used to assess the publishing bias of articles. Results Totally 11 articles were selected, which involved 1 344 cases and 3 885 controls. The results of meta-analysis showed that there were significant differences between the two groups for the dominant, recessive, and addictive genetic models, and the pooled OR (95%CI) were 1.19(1.02~1.39), 1.21(1.00~1.45), 1.27(1.02~1.58), respectively. The differences were statistically significant (P<0.05). Conclusion The Asn680Ser polymorphisms of FSHR gene are associated with the susceptibility of PCOS. Ser allele of Asn680Ser is a risk factor of the PCOS for the dominant, recessive, and addictive genetic models.

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    Application value of dual energy scan technique with selective photon shield for computed tomography angiography diagnosis of intracranial aneurysms
    YANG Bin, ZHAO Wei, WU Li, et al
    2014, 34 (4):  533. 
    doi: 10.3969/j.issn.1674-8115.2014.04.026

    Abstract ( 848 )   PDF (526KB) ( 1019 )  

    Objective To investigate the clinical value of dual energy (DE) scan technique with selective photon shield (SPS) for the CT angiography (CTA) diagnosis of intracranial aneurysms. Methods Seventy patients with clinically suspected intracranial aneurysms were examined by the CTA and three dimensional digital subtraction angiography (3D-DSA) one week later. SPS-DE technology was used for CT scanning and the image quality of SPS-DE-CTA was subjective rated. The locations and numbers of aneurysm, display degree of aneurysmal neck, long and short diameters of aneurysm, and sizes of aneurysmal neck indicated by two methods were compared and analyzed. Results The image quality of SPS-DE-CTA was over 4 scores, which could satisfy the diagnostic requirements. The 3D-DSA was referred to as the diagnostic standard and the sensitivity, specificity, prediction values of the positive and negative, and accuracy of detecting aneurysms by the SPS-DE-CTA were 100%. And 63 aneurysms were detected by the SPS-DE-CTA and the mean long diameter, short diameter, and sizes of aneurysmal neck were (4.96±1.47)mm, (4.01±1.59)mm, and (3.02±0.75)mm, respectively. The 3D-DSA also detected 63 aneurysms and the mean long diameter, short diameter, and sizes of aneurysmal neck were (4.89±1.52) mm, (3.89±1.56) mm, and (2.91±0.73)mm,respectively. With 3D-DSA as the diagnostic standard, the differences of locations and numbers of aneurysms and measurements of two diagnostic methods were not statistically significant (P>0.05). The mean long diameter (r=0.963), short diameter (r=0.968) of aneurysm, and mean size of aneurysmal neck (r=0.856) measured by two diagnostic methods were well correlated (P=0.000). Conclusion The accuracy of SPS-DE-CTA for diagnosing intracranial aneurysms is high and can be used as a routine non-invasive screening method.

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    Treatment of medium-to-severe rigidity congenital kyphoscoliosis by posterior hemivertebral resection and segmental multi-rod instrumentation
    LI Bo, YU Yu, LU Min-peng, et al
    2014, 34 (4):  537. 
    doi: 10.3969/j.issn.1674-8115.2014.04.027

    Abstract ( 992 )   PDF (579KB) ( 1226 )  

    Objective To evaluate the early clinical outcome of one-stage posterior hemivertebral resection and segmental multi-rod instrumentation for the treatment of medium-to-severe rigidity congenital kyphoscoliosis caused by a single hemivertebrae. Methods Seventeen patients with medium-to-severe rigidity congenital kyphoscoliosis were surgically treated by the posterior hemivertebral resection and segmental multi-rod instrumentation. Hemivertebrae were sited in T10(2 cases), T11(4 cases), T12(5 cases), L1(3 cases), and L2(3 cases). The preoperative scoliotic Cobb angles were (67.9±8.2)° and kyphotic Cobb angles were (73.0±10.6)°. Results All patients underwent surgeries safely and there were no death or neurological injuries occurred. The operation time was 4.0-7.5 h (averaged 5.6 h) and the perioperative bleeding was 500-3 000 mL (averaged 1 050 mL). One patient suffered from left pleura tearing during capitulum costae resection and incurred hemopneumothorax. The patient was treated by chest cavity closed drainage and recovered completely after one week. All cases were followed up for 12-35 months (averaged 19.4 months). Bony fusion was achieved in all patients and no pseudoarthrosis and implant failure was observed. The Cobb angles of scoliosis and kyphosis after one week of operations and at the time of the last follow-up were much better than those before the operations. The differences were statistically significant (P<0.05). Conclusion The one-stage posterior hemivertebral resection and segmental multi-rod instrumentation is feasible and effective in correcting scoliosis and kyphosis for the treatment of medium-to-severe rigidity congenital kyphoscoliosis caused by a single hemivertebrae.

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    Original article (Preventive medicine)
    Investigation and analysis of anemia and levels of related micronutrients during gestation period
    YANG Ting, GU Yan, WEI Xiao-ping, et al
    2014, 34 (4):  542. 
    doi: 10.3969/j.issn.1674-8115.2014.04.028

    Abstract ( 766 )   PDF (252KB) ( 1066 )  

    Objective To investigate the anemia and levels of related micronutrients of pregnancy women and analyze the effects of anemia at different stages of gestation on physical indexes of neonates. Methods The fasting venous blood of 5 mL was drawn from 299 pregnancy women of Tongliang Country, Chongqing for detecting the hemoglobin and micronutrients related to anemia. The pregnancy outcomes and physical indexes of neonates were followed up. Results Among 299 pregnant women, the rates of vitamin A deficiency, marginal vitamin A deficiency, iron deficiency, and vitamin B12 deficiency were 11.0% (33/299), 43.8% (131/299), 5.7% (17/299), and 0.3% (1/299), respectively. The incidence of anemia during gestation period was 24.5%(62/253). The levels of plasma vitamin A and iron of early pregnancy anemia group were significant lower than those of non-anemia group (P<0.05). The birth weights of neonates of late pregnancy anemia group were statistically lower than those of non-anemia group (P<0.05). Conclusion The incidences of anemia, vitamin A deficiency, and iron deficiency during gestation period are still high in Tongliang Country, Chongqing. The guidance of gestation dietary should be strengthened and the anemia should be treated in time so as to ensure the health of both mothers and fetuses.

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    Review
    Advances of pathogenesis of latent autoimmune diabetes in adults
    LU Jun, HOU Xu-hong, JIA Wei-ping
    2014, 34 (4):  546. 
    doi: 10.3969/j.issn.1674-8115.2014.04.029

    Abstract ( 1840 )   PDF (305KB) ( 1092 )  

    Latent autoimmune diabetes in adults (LADA) is a form of adult-onset autoimmune diabetes that resembles type 2 diabetes. However, it shows a later onset and slowly progression towards insulin requirement. LADA accounts for 5.9% to 9.2% in newly diagnosed patients with phenotypic type 2 diabetes in China. The pathogenesis of LADA has become one of the hot research topics in recent years. Progresses have been made in aspects such as genetic susceptibility, autoimmune reaction, and environmental factors and so on. Studies show that non-HLA gene, cellular immunity, and nonspecific immune reaction etc. are relevant to LADA. Thorough research on the pathogenesis of LADA is helpful for understanding it's clinical characteristics, early prevention and diagnosis, proper treatment, and even exploring new therapeutic methods.

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    Advances of protein kinase C beta and diabetic nephropathy
    ZHAO Ming-ming, LIU Li-mei
    2014, 34 (4):  551. 
    doi: 10.3969/j.issn.1674-8115.2014.04.030

    Abstract ( 1185 )   PDF (340KB) ( 1021 )  

    Two isoforms of protein kinase C (PKC), i.e. PKC-βI and -βⅡ, which are encoded by the PRKCB1 gene, play important roles in the development and progression of diabetic nephropathy through the PKC signaling pathway. PKC-β inhibitor can reduce the thickness of glomerular basement membrane and microalbuminuria to protect the renal functions of diabetes patients. Polymorphisms and variants of PRKCB1 gene are relevant to increasing the risk of diabetic nephropathy and end stage renal disease by affecting its transcriptional activity, increasing insulin resistance, and promoting endothelial oxidative stress. This paper reviews the research progresses on the relationship between PKC-β and diabetic nephropathy.

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    Exosomes and renal physiology and diseases
    CHEN Chun-yuan, NIU Xin, WANG Yang
    2014, 34 (4):  556. 
    doi: 10.3969/j.issn.1674-8115.2014.04.031

    Abstract ( 945 )   PDF (382KB) ( 1097 )  

    Exosomes are small membrane vesicles secreted into extracellular matrix after the fusion of intracellular multivesicular bodies and cell membrane and their diameters are between 30-100 nm. Exosomes contain mRNAs, miRNAs, and proteins of source cells that can represent biological information of source cells, so they are potential biological markers. Effects of exosomes on signal transduction, inducing anti-tumor responses, and immunologic tolerance responses, etc. become research hotspots in recent years and have been used in new treatments. The urinary exosomes are closely related to the physiological functions and diseases of kidneys. However, the research in this field is only in early stages. This review aims to summarize the research developments of biological characters, physiological functions, separation and purification of exosomes, and their effects as biological markers and treatment values for kidney diseases.

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    Advances of nonylphenol toxicity on the female reproductive system
    CHENG Shu-qun, ZHANG Zhi-hao, XIA Yin-yin
    2014, 34 (4):  562. 
    doi: 10.3969/j.issn.1674-8115.2014.04.032

    Abstract ( 904 )   PDF (344KB) ( 998 )  

    Nonylphenol (NP) is an environmental endocrine disrupting chemical (ED), which mainly comes from the biodegradation of nonylphenol ethoxylates (NPEOs). As nonionic surfactants, NPEOs are widely used in chemical products, such as detergent, lubricant additives, and plastics additives. NP has estrogenic activity, so it may influence and harm the female reproductive system. Although the mechanism of its estrogenic activity is not very clear,the adverse effects of NP on human bodies should not be ignored. This paper reviews the researches on the reproductive toxicity of NP, and provides evidence for reducing the NP emission and finding alternatives.

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