Table of Content

21 October 2012, Volume 33 Issue 5

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肿瘤学专题

Fast and scalable production of cancer-killing complex from recombinant human alpha-lactalbumin and oleic acid

ZHANG Yi-bo;ZENG Rui-xia;NIU Jing;ZHENG Shao-peng;JIA Hong-ti;DING Wei

2012, 33(5):  557-564.  doi:10.3969/j.issn.1006-7795.2012.05.001

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Objective Human alpha-lactalbumin made lethal to tumor cells (HAMLET) is a novel potent tumoricidal agent that selectively induces apoptosis-like cell death in a variety of cancers.Methods As the sufficient amount and concentration of human alpha-lactalbumin (HLA) to form HAMLET is critical for its anti-tumor activity, mass production and rapid purification of recombinant HLA protein is highly desired. We first constructed a cDNA library of MCF-7 cell, known to secrete mature HLA peptides. Then amplified the full-length of HLA coding sequence by PCR, and cloned it into a pET30a(+) vector with an C-terminus His-tag. The His-rHLA was highly expressed in BL21 E coli cells with the induction of IPTG and purified by Ni-NTA affinity chromatography. The rHLA was refolded in an in vitro refolding buffer, de-calcinated with EDTA treatment, and then reacted with oleic acid (OA) water suspension under heated conditions to form the HAMLET complex. Results By comparing our HAMLET product with a reference preparation (BAMLET) from bovine alpha-lactalbumin and OA, we found that our preparations of HAMLET have a similar UV spectrum and a comparable tumoricidal activity as determined by cell viability assays and morphologic observations.Conclusion The cost-effectiveness and scalability of HAMLET production using recombinant HLA can be extremely useful for the further investigation of mechanistic studies of HAMLET functions, and may also be potentially considered as a practical anti-cancer agent for therapeutic trials.

Preparation of folic acid coupled nano-paclitaxel drug

TONG Ling-xia;LI Hong-xia

2012, 33(5):  565-568.  doi:10.3969/j.issn.1006-7795.2012.05.002

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Objective To prepare the folic acid coupled nano-paclitaxel drug for targeted tumor therapy. Methods Nano-paclitaxel was prepared by polycarbonate membrane dispersion-extrusion. The method of ultrasonic emulsification-solvent evaporation was adopted to prepare DSPE-PEG2000-FA micelle. Co-incubation method was used to prepare DSPE-PEG2000-FA modified folic acid coupling nano-paclitaxel. The mean diameter of folic acid coupling nano-paclitaxel drugs and the encapsulation efficiency were determined by zetasizer and elution curve of drug. Results Compared with the diameter of nano-paclitaxel particle［(121.6±12.7) nm］and polydispersity index (PDI) (0.262±0.031), the mean diameter of folic acid coupling nano-paclitaxel drugs ［(140.5±10.3) nm］ and PDI (0.263±0.061) were slightly larger, but the difference was not statistically significant (t=2.013; P=0.114). In contrast to the encapsulation efficiency of the crude drugs (nano-paclitaxel drugs) 99%, the encapsulation efficiency of folic acid coupling nano-paclitaxel drugs was as high as 97% with no significant decline, which ensures purity and effectiveness of the drugs. Conclusion The novel formulation of FR-targeted folic acid coupling nano-paclitaxel is reported. This formulation has good drug loading properties, drug encapsulation efficiency, and exhibits excellent colloidal stability.

Claudin-7—a potential tumor suppressor gene

DING Lei;GAO Hong;ZHU Yu-bing;LI Wen-bin

2012, 33(5):  569-574.  doi:10.3969/j.issn.1006-7795.2012.05.003

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Objective To investigate the phenotype of Claudin-7 knockout mice (KO) and potential anti-tumor function of Claudin-7 gene. Methods DNA extracted from mouse tails were used to determine mouse genotype by PCR methods, and Claudin-7 protein expression in various tissues was detected by Western blotting, and pathomorphological changes in intestine were observed by HE staining. Interaction between protein Claudin-7 and intergrin α2 were detected by co-immunoprecipitation method.Claudin-7 protein expression in each organ and protein C-fos, C-jun, COX-2 expression in intestine of WT and KO mouse were measured by Western blotting, as well as Claudin-7 expression at different degrees of differentiation of colon cancer tissues.Results Mouse failing to grow could be found 4 days after birth for Claudin-7 knockout mice (KO), which would die within about 7 days after birth. Claudin-7 could be detected strongly in various tissues such as intestine, stomach, lung, bladder, skin, thymus and kidney, but ubiquitously expressed along the whole intestine including small and large intestine. Moreover, serious intestinal mucosal disruption including severe epithelial cell loss, vacuolation and infiltrated with inflammatory cells such as neutrophil granulocyte could be viewed by light micrographs with H&E-stained, but there were no obvious changes in other tissues except light inflammatory cells infiltration. C-fos, C-jun and Cox-2 protein expression was upregulated significantly in intestine of Claudin-7 knockout mouse as compared with that in normal mouse (WT), as well as Claudin-7 protein expression downregulated in poorly differentiated and liver metastasis tissues of colonic carcinoma. Importantly, Claudin-7 and intergrin α2 could precipitate together by co-immunoprecipitation (Co-IP) method. Conclusion Mouse intestinal inflammation model was modulated by Claudin-7 knockout successfully, and may be a potential tumor suppressor gene.

Expression of mRNA of matrix metalloproteinase 11 and Moesin and its relevance to metastasis and prognosis in colorectal carcinoma

ZHANG Li-ping;PU Hong-wei;CHEN Xiao;LI Xiao-mei;JING Hua-lan;LIU Xiao-shan

2012, 33(5):  575-580.  doi:10.3969/j.issn.1006-7795.2012.05.004

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Objective To determine the expression of mRNA of matrix metalloproteinase 11 (MMP-11) and Moesin in colorectal carcinoma tissue, and to investigate the correlation between its expression and tumor metastasis and prognosis. Methods The expressions of mRNA of MMP-11 and Moesin in 68 tissues from patients with colorectal carcinoma and 40 tissues with normal colorectal mucosa were detected with in situ hybridization. Results The positive expression of mRNA of MMP-11 and Moesin in colorectal carcinoma tissue was 69.1%, and 60.3% respectively, which were both significantly higher than that in normal colorectal mucosa (P<0.05). The expression of mRNA of MMP-11 and Moesin was correlated with histologic differentiation, lymph node metastasis and clinical staging in patients with colorectal carcinoma. The expression of MMP-11 mRNA was also correlated with the depth of invasion of colorectal carcinoma into tissues (P<0.05). The 5-year survival rates were 46.8% and 75% in colorectal carcinoma patients with positive and negative expression of MMP-11 mRNA, respectively. The difference was statistically significant (P<0.05). There were no significant differences on the 5-year survival rates between the colorectal carcinoma patients with positive and negative expression of Moesin mRNA. Conclusion The expressions of mRNA of MMP-11 and Moesin are correlated with the progression and metastasis of colorectal carcinoma, and MMP-11 may be used as a predictor for prognosis of colorectal carcinoma.

Efficacy of erlotinib applied after gefitinib failure on the advanced adenocarcinoma of non small cell lung cancer

SONG Yu-guang;ZHAO Yan-jie;ZHOU Lei;AN Guang-yu

2012, 33(5):  581-585.  doi:10.3969/j.issn.1006-7795.2012.05.005

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Objective To evaluate the efficacy and safety of erlotinib on the advanced adenocarcinoma of non small cell lung cancer(NSCLC) patients after failure of gefitinib treatment and study the relationship between efficacy and clinical characteristics. Methods A retrospective analysis of advanced NSCLC patients who were previously treated with gefitinib and showed progression from June 2008 to February 2009. And the patients received erlotinib 150 mg/d until disease progression or the drug became intolerable because of toxicity. The efficacy, side effects and the relationship between efficacy and the epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitors (TKi)s and clinical characters were observed. Results A total of 22 NSCLC patients were enrolled in this study. Among 22 patients, two had partial response and seven had a stable disease, resulting in an Objective response rate of 9%, and a disease control rate of 40.9%. The overall survival of those who had no benefit vs. those who had benefit were 82 days and 192 days respectively. The patients who had obtained disease control with erlotinib, showed a longer time to progress (TTP) (112 vs. 45.5 days, P<0.05). The most common toxic effects were skin rash and diarrhea. Conclusion Erlotinib seems to be effective in patients with advanced NSCLC after failure of gefitinib, especially in those who had benefit from prior gefitinib treatment.

Kidney-sparing surgery to treat the primary transitional cell carcinoma of ureter

ZHANG Ji-Wei;WANG Hai-Tao;WANG Jian-Jun;BAI Yan;XIA Ming

2012, 33(5):  586-588.  doi:10.3969/j.issn.1006-7795.2012.05.006

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Objective To evaluate the clinical treatment and prognosis of the primary transitional cell carcinoma of ureter.Methods Retrospective review of 19 cases who underwent kidney-sparing surgery for treatment of the primary transitional cell carcinoma of ureter was carried out. There were 10 males and 9 females with the mean age of 65.6 years. 14 cases had gross hematuria and 2 cases had flank pain and in 3 cases renal hydronephrosis was found incidentally by B-ultrasound. Results All cases were treated with kidney-sparing surgery. In 15 cases ureteral segmental resection was performed, in 4 of these cases terminoterminal anastomosis and in 11 cases ureterocystostomy with bladder cuff excision were performed. In 4 cases tumor were resected by ureteroscopy. Postoperative pathological findings confirmed the diagnosis of transitional cell carcinoma. Pathological staging showed T_a (1 cases), T₁ (5 cases), T₂ (9 cases), T₃ (4 cases) and grading showed G₁ (5 cases);G₂ (8 cases); G₂-G₃ (3 cases);G₃ (3 cases). Seventeen cases (89.5%) were followed up for 3~132 months. The overall 5-year survival rate was 58.8%. Bladder recurrences occurred in 29.4% of patients within 6~24 post-operation months and 29.4% patient showed ipsilateral upper urinary tract transitional cell carcinoma recurrences within 12~72 post-operation months. Three cases died of non-tumor illness within 12~36 months postoperatively. Conclusion The primary transitional cell carcinoma of ureter may be uncommon and has poor prognosis. Kidney-sparing surgery is a feasible treatment option in patients with lower stage and grade. The long-term follow up should be meticulous, because the recurrence rate is high.

Temozolomide adverse events and coping strategies in malignant glioma patients with concurrent chemoradiotherapy

KANG Xun;LI Shan;XIE Zheng-zheng;ZHAO Yan-jie;JIANG Ni;ZHOU Lei;LI Wen-bin

2012, 33(5):  589-593.  doi:10.3969/j.issn.1006-7795.2012.05.007

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Objective Radiotherapy has been of key importance to the treatment of malignant gliomas for decades, and the ability to focus the beam and tailor it to the irregular contours of brain tumors and minimize the dose to nearby critical structures with intensity modulated or image-guided techniques has improved greatly. Temozolomide, an alkylating agent given in simple oral route of administration,is used in conjunction with and after radiotherapy. This study aimed to evaluate the toxic effects of temozolomide when used incombination with radiotherapy, to observe the side effects of temozolomide, evaluate the clinical safety of the drug, and improve the quality of life in patients with glioma.Methods Based on the Common Terminology Criteria forAdverse Events (CTCAE) Version 4.0, the authors observed the toxicity of temozolomide in patients with concurrent chemoradiotherapy, and take active measures to deal with the toxicity. Results here were 95 patients who received concurrent chemoradiotherapy, 20 patients had the symptoms of nausea, vomiting and loss of appetite, according to CTCAE-V4.0, 12 cases were grade 1, 8 cases were grade 2. 9 patients had neutropenia, 6 of them were grade 1, 3 cases were grade 2. In the aspect of thrombocytopenia, 3 cases were grade 1, 1 case was grade 2. Mucocutaneous adverse reactions were observed in 7 cases, 6 cases were grade 1, 1 case was grade 2. One patient had symptoms of palpitation, the evaluation was grade 2. All patients had mild symptoms of adverse drug reactions, but the symptoms could significantly relieve after symptomatic treatment and withdrawal of the treatment. Conclusion Temozolomide is commonly used in the treatment of malignant glioma, the toxic and side effects were observed during the process of concurrent chemoradiotherapy, the toxic and side effects were minor, and can be relieved obviously after symptomatic treatment. Therefore, temozolomide is a safe drug for malignant glioma treatment.

The influence of human serum insulin-like growth factor-1 on the endometrium in female breast cancer with tamoxifen treatment

REN Hai-ying;ZHAI Jian-jun;GAO Hong

2012, 33(5):  594-596.  doi:10.3969/j.issn.1006-7795.2012.05.008

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Objective To study the effect of human serum insulin-like growth factor-1(IGF-1) on the endometrial thickening in women with breast cancer who accepted tamoxifen treatment. Methods Thirty-nine women with breast cancer treated with tamoxifen were enrolled and screened for the endometrial thickness by ultrasound every 3 months till 24 months after tamoxifen treatment. Spontaneously their blood serum was prepared for IGF-1 detection. When the endometrial thickness of patients was 0.5 cm or thicker by ultrasound, the research stopped. There were 26 cases who had the thickness less than 0.5 cm as A1 group. A2 group was comprised of the left 13 cases whose endometrial thickness was 0.5 cm or thicker.Human serum IGF-1 was detected by immunoradiometric assay(IRMA). Results The rate of endometrial incrassation was about 33.33% (13/39). The average age of A2 group was younger than that of A1 group significantly (P<0.05). The level of serum IGF-1 in all the patients decreased gradually as tamoxifen treatment extended. Compared with A2 group,the variation of serum IGF-1 level in A1 group was significantly greater in the sixth month after tamoxifen treatment (P<0.05). In the twenty-first month, the difference between two groups still existed but was not significant (P>0.05).Conclusion Tamoxifen treatment could decrease the serum IGF-1 level of women with breast cancer. The endometrial incrassation caused by tamoxifen treatment might be associated with the slower decrease of serum IGF-1 level.

Current status and prospective of cancer immunotherapy

REN Jun

2012, 33(5):  597-601.  doi:10.3969/j.issn.1006-7795.2012.05.009

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Increasing knowledge has increased awareness of roles of immunotherapy in cancer treatment. Such immunomodulation targeting specific immunopathways has risen the understandings that more and more methods could be incorporated into the clinical applications. The immunotherapy eliciting specific cellular immune response against cancer cells might result in tumor cell lysis and subsequently enhancing ability of antigen presenting cells and shows synergism with the cytotoxicity of chemotherapy.

艾滋病神经认知损害及疫苗学研究

Role of oxidative damage in HIV-related neurocognitive impairment

DING Wei;ZHANG Yu-lin;QIAO Lu-xin;SONG Feng-li;XU Shu-ying;CHEN De-xi

2012, 33(5):  602-609.  doi:10.3969/j.issn.1006-7795.2012.05.010

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Objective Oxidative stress has been suggested to play a key role in the neuropathogenesis of HIV infection. HIV proteins (gp120, Tat), and proinflammatory cytokines can trigger the production of reactive oxygen species (ROS), resulting in DNA and RNA lesions. Among all the lesions induced by ROS, one of the most frequently occured lesions in DNA and RNA is 8-hydroxydeoxyguanosine (8-oxoG). Here, we report accumulated DNA oxidative damage induced by ROS in the central nervous system (CNS) in tissue from neuro-AIDS patients. Methods The frontal cortex of autopsy tissue from HIV-1 infected patients was adopted for analysis for HIV-1 subtype, nuclear and mitochondrial DNA lesions by immunofluorescence staining, qPCR and sequencing of PCR cloning. Results This study provides evidence that HIV infection in the CNS leads to nuclear and mitochondrial genomic DNA damage in the brain. High level of nuclear and mtDNA 8-oxoG damage were identified in the cortex autopsy tissue of HIV-associated neurocognitive disorder (HAND) patients. Increased accumulation of mtDNA mutations and depletion occurs in brain tissue in a subset of HAND cases, and is significantly different from that observed in control cases. Conclusion These findings suggest that higher level of ROS in the CNS of HAND patients would contribute to the HIV induced neuro-inflammation and apoptosis of neuronal and glial cells.

An initial screening for HIV-1 associated neurocognitive disorders in HIV-1 infected patients in China.

SONG Feng-li;ZHANG Yu-lin;QIAO Lu-xin;DING Wei;XU Shu-ying;ZHANG Tong;WU Hao;CHEN De-xi

2012, 33(5):  610-615.  doi:10.3969/j.issn.1006-7795.2012.05.011

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Objective To initially screen for the HIV-1 associated neurocognitive disorders (HAND) in HIV-1 infected patients in China. Methods The International HIV Dementia Scale and a neuropsychological test battery were administered for screening and diagnosis of HAND in 134 HIV-1 infected patients in China. Subjective complaints, CD₄ count and viral loads in both blood plasma and cerebrospinal fluid(CSF) were correlated with diagnosis of HAND. Results The prevalence of HAND in Chinese HIV-1 infected patients was 37%. The presence of HAND was associated with cognitive and behavior disorder complaints (4.9 and 4.1 fold higher than those without HAND, respectively). The level of viral load in CSF correlated with that in blood, but neither viral load (both in CSF and in blood) nor CD₄ counts was found significantly different between HAND and non-HAND patients. Conclusion The prevalence of HAND in Chinese HIV-1 infected patients was 37%. Cognitive impairment is major complaint in HAND patients, followed by behavior disorder. None of viral load (viral load in CSF or in blood) and CD₄ counts could predict the occurrence and development of HAND. Larger sample size, longitudinal observation and additional laboratory characterizations are needed to better characterize neurocognitive function among HIV-infected people in China.

艾滋病神经认知损害及疫苗学研究

Immune protective effects induced by HIV-1 Nef recombinant overlapping peptides in mice

ZHANG Hong-wei;ZHANG Tong;XIA Wei;WU Hao

2012, 33(5):  616-620.  doi:10.3969/j.issn.1006-7795.2012.05.012

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Objective To investigate the effects of immune responses induced by HIV-1 Nef recombinant overlapping peptides in mouse models.Methods BALB/c and C57BL/10 mice were immunized with HIV-1 Nef recombinant overlapping peptides and corresponding protein with 5 mice in each group. Spleen mononuclear cells (SMC) were isolated to detect specific cell responses by ELISPOT and flow cytometry. Large doses of Nef recombinant vaccinia virus challenge test was used to measure the protection of recombinant overlapping peptides to immunized mice.Results In C57BL/10 mice, ELISPOT results in adjuvant group were negative, LAI Nef-specific cellular immune responses in overlapping peptide group and the corresponding protein group were (145.7 ± 36.2) SFU/10⁶ SMC and (24.2 ± 10.2) SFU/10⁶ SMC respectively (P=0.001), (148.8 ± 50.4) SFU/10⁶ SMC and (19.8 ± 9.0) SFU/10⁶ SMC in BALB/c mice (P=0.004). NL4-3 Nef-specific cellular immune responses in overlapping peptide group and the corresponding protein group were (104.0 ± 33.8) SFU/10⁶SMC and (20.7 ± 9.5) SFU/10⁶ SMC (P=0.004) respectively. Percentage of Nef-specific CD₄⁺ and CD₈⁺ cells induced by recombinant overlapping peptides were 1.53 and 0.80. In virus challenge test, survival rates of overlapping peptide group, the corresponding protein group, adjuvant group and blank control group were 80%, 40%, 20% and 0% respectively. Conclusion Recombinant overlapping peptides can induce strong, protective, broad-spectrum specific cellular immune responses, with cross-reactive to different strains of Nef. Effects of immunization with recombinant overlapping peptide are stronger than those of the corresponding protein.

Sentinel surveillance of female sex workers in Luannan County in 2011

LIU Zhi-jie;JIANG Li;WANG Chun-bo;LIU Ting-ting

2012, 33(5):  621-624.  doi:10.3969/j.issn.1006-7795.2012.05.013

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Objective To understand epidemiologic characteristics and acquired immunodeficiency syndrome(AIDS) epidemic trend in female sex workers in Luannan County. Methods Questionnaires investigation and serological testing were conducted among 400 female sex workers. In accordance with the requirements of the National AIDS sentinel surveillance program. Results The average age of the female sex workers was 28.62. In all these female sex workers, unmarred accounted for 57.25%. Those from Hebei Province accounted for 67.00% and those from other provinces accounted for 33.00%. The subjects who received only junior high school education accounted for 60.00%. AIDS prevention and awareness rats was 88.00%. Rate of condom use during the last sexual intercourse was 56.75%. Only 4 subjects had drug use behavior, but did not inject. In the last year, 298 subjects (74.50%) received the knowledge about AIDS prevention services. Two cases were positive for syphilis antibody and 9 cases were positive for hepatitis C virus(HCV) antibody positive in serological testing, but none of the cases was human immunodeficiency virus(HIV) positive. Conclusion There was a gap between female sex workers and normal control in rates of condom use and AIDS awareness. The methods of behavioral intervention should be changed, peer education services should be strengthened to promote their behavior changes. Meanwhile, education for prevention of sexually transmitted diseases should be strengthened.

Progress in studies on the role of cytokine in pathogenesis and treatment of HIV infection

ZHANG Mei;WU Hao;ZHANG Hong-wei

2012, 33(5):  625-628.  doi:10.3969/j.issn.1006-7795.2012.05.014

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Immune activation is an important feature of HIV infection. CD₄ T-cell immune activation is driven by homeostatic response and inflammation, while CD₈ T cell immune activation is driven by HIV replication and inflammation. Interleukin-7(IL-7), type I interferon and inflammatory cytokines play an important role in the pathogenesis of HIV infection. The role of γc cytokines and interferon alpha in the treatment of HIV infection is still in clinical research stage, which will be helpful for the recovery of immune cells.

基础研究

Enhancing effect of mutant α-synuclein on neurite outgrowth of rat primary cultured neuron

WANG Peng;XU Jie;LI Xin;HE Xin;LI Yao-hua;YU Shun

2012, 33(5):  629-633.  doi:10.3969/j.issn.1006-7795.2012.05.015

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Objective To investigate the effect of A53T and A30P on the neurite outgrowth of brain neurons and indicate its function, explore the mechanism of Parkinson's disease. Methods Neurons isolated from the neocortex of newborn Wistar rats were cultured and corresponding proteins were added into the culture medium to observe the effect of the protein on the neurite outgrowth of the neurons. A53T, A30P and α-synuclein were added into the culture system of neural cells, and the different promoting effect of neurite outgrowth was compared with that of control groups. Western blotting assays and immunofluorescence staining assay were used to confirm whether the result is special. Inverted phase contrast microscope,and photographs were applied to analyze the results with software. Results The mean neurite length of the neurons treated with α-Syn was significantly longer than that of A53T and A30P group neurons(P<0.05). There was no significant difference between A53T and A30P groups with control group(P>0.05). Increased concentration of α-synuclein could enhance this effect. The result of Western blotting and immunofluorescence staining assay showed that α-synuclein could enter the neural cell and enhance the neurite outgrowth. Blockade with monoclonal antibody 3D5 showed that the blocking of α-Syn could significantly inhibit the effect (P>0.05). Conclusion α-Synuclein can enhance neurite outgrowth of primary cultured neuron in a dose-dependent manner. But its mutants A53T and A30P did not show such effect.

Effects of acupoint injection of Radix Astragali on Th1 and Th2 type cytokines in sport fatigue model rat

LI Jun-fang;ZHANG Qiu-xia;ZHAO Hui;ZHANG Qi;WANG Hai-zheng;JIANG Ming-yin

2012, 33(5):  634-637.  doi:10.3969/j.issn.1006-7795.2012.05.016

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Objective To observe the effects of the acupoint injection of Radix Astragali Astragali on Th1 and Th2 type cytokines in Sport Fatigue Rats. Methods Totally 24 rats were divided into normal group, model group, acupoint injection of Radix Astragali group and acupoint injection of physiological saline group randomly, 8 rats in each group. The rats were injected with Radix Astragali and physiological saline in zusanli (ST36) acupoint respectively in acupoint injection of Radix Astragali group and acupoint injection of physiological saline group per-day after the swimming training. After the swimming training and the 10 days treatment, all the rats were injected with chloral hydrate for anesthesia. The blood was taken from each rat's heart and the contents of IL-2, IFN-γ, IL-4 and IL-10 in blood serum were examined. Results The serum levels of IL-2 and IFN-γ in model group decreased in comparison with those of normal group while The serum levels of IL-2 and IFN-γ in acupoint injection of Radix Astragali group increased obviously in comparison with those of model group(P<0.01). Conclusion Acupoint injection of Radix Astragali can prevent the rats from losing weight after swimming and can balance cytokines between type Th1 and Th2 cell.

Lateralization of brain processing in animal/plant categorization task

WANG Pei-pei;CHEN Andrew

2012, 33(5):  638-642.  doi:10.3969/j.issn.1006-7795.2012.05.017

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Objective Categorizing external stimuli in cognitive processing is a basic principle in the brain mechanism. Numerous studies have suggested different brain mechanisms in processing natural vs. artificial objects. However, few studies have explored the difference in brain mechanism in processing animals and plants, although they play different roles in human evolution. To examine the difference in their processing mechanisms, we employed neuropsychological approach to compare the speed of judgment on nouns belonging to animals or plants. We also examined the relationship between functional lateralization of the brain and the difference in processing animals and plants. Methods Twenty-five right-handed participants (healthy college female subjects, 20~25 years old) were asked to categorize 120 single-character nouns belong to either animals or plants. The subjects were instructed to respond with speech in one session, and response with button presses in the other two. In the first button-press session, left hand corresponded to animals, and right hand corresponded to plants. The correspondence was switched in the last session. Results In the speech-response session, the reaction time (RT) in responding to animals was significantly shorter than that to plants (t=-3.77, P<0.001). In the button-press sessions, a significantly faster RT for animals than plants (t=-3.98,P<0.001) was observed with the right-hand response. Conclusion Our study provided primary but initial evidence showing the brain mechanisms in processing animals and plants are different. Relationships between the functional lateralization of the brain and the processing mechanisms for animals and plants were also observed.

Effects of triptolide on expression of inducible nitric oxide synthase and production of nitrogen monoxide in microglia cells induced by β-amyloid

WANG Hui-ling;ZHOU Xiao-chun;MA Chun-hu;WANG Bing;WANG Xiao-min

2012, 33(5):  643-646.  doi:10.3969/j.issn.1006-7795.2012.05.018

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Objective To investigate the effects of triptolide (T10) on expression of inducible nitric oxide synthase (iNOS) and production of nitrogen monoxidum (NO) in microglia cells induced by β-amyloid(Aβ)_1-42. Methods The microglia cells were pre-treated with 10-11-10-8 mol/L T10 for 12 h before 10 μmol/L Aβ_1-42 were added, and incubated for 12 h together. The production of NO was determined by Griess reaction, and the expression of iNOS was determined by Western blotting. Results Expression of iNOS and production of NO in Aβ group were significantly higher than those in control group(P<0.01). T10 treatment reduced expression of iNOS and production of NO obviously induced by Aβ from microglia cells(P<0.05).Conclusion T10 significantly inhibited expression of iNOS and production of NO in microglia cells induced by Aβ. T10 might provide a novel therapy for AD.

Construction and identification of an expressing vector for a large human naive phage antibody library

PAN Bo;FU Wen-zhuo;WANG Xiao-na;ZHANG Bao-zhong;AN Xiao-ping;LIU Da-bin;LI Cun;JIANG Huan-huan;CHEN Bin;TONG Yi-gang

2012, 33(5):  647-652.  doi:10.3969/j.issn.1006-7795.2012.05.019

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Objective To construct an expression vector that can be applied to the construction of large Fab fragment phage display library.Methods BssH II restriction site in phagemid vector pDF was mutated to Bgl Ⅱ restriction sites by site-directed mutagenesis techniques, and a suicide gene SacB was inserted into both the heavy and light chain region, resulting in phagemid vector pDF-D-SacB. Heavy chain (VH) and light chain (VL) genes of anti-hepatitis B surface antigen (HBsAg) antibody were inserted into the phagemid vector pDF-D-SacB separately. The recombinant VH and VL phagemids were transformed into Trans1-Blue E. coli by electroporation respectively. By co-infecting the VH and VL phagemids into bacteria BSl365 at high multiplicity of infection, the recombinant phagemid containing both the VL and VH genes was obtained. After infecting trans1-Blue E. coli with the recombinant phage, the recombinant anti-HBsAg antibodies were assayed by ELISA. Results By inserting SacB gene into the light and heavy chain regions of pDF and modifying the cloning sites of the vector, a new phagemid vector pDF-D-SacB was constructed. The subsequent test showed that the constructed vector can express functional Fab phage antibodies, and can also allow the Cre-LoxP mediated recombination in bacteria cell. ConclusionA suicide gene containing phagemid vector pDF-D-SacB was applicable to constructing large phage display antibody library.

Investigation on the synthetic reaction of glucopyranosides

ZHANG Jian-wei;FAN Yuan-jie

2012, 33(5):  653-655.  doi:10.3969/j.issn.1006-7795.2012.05.020

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Objective To investigate synthesis of thymine nucleoside.Methods The reactions of phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-glucopyranoside and phenyl 3,4-Di-O-benzoyl-6-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-glucopyranoside with the silylated thymine were allowed to occur in dichlormethane. Results The 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-glucopyranosideand phenyl 3,4-Di-O-benzoyl-6-O-acetyl-2-deoxy-2-phthalimido-1-thio-glucopyranoside reacted with the silylated thymine to form N-β-glycoside. Conclusion Thus we have explored the reaction glucopyranosides with thymine. phenyl 3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-glucopyranoside and phenyl 3,4-Di-O-benzoyl-6-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-glucopyranoside furnished N¹-β-glycosideand N³-β-glycoside.

Association of WHO2004 pathological classification of bladder urothelial tumors with the outcome

LUO Jing;ZHANG Jin-sheng;WANG Cui-zhi;LIU Ning

2012, 33(5):  656-660.  doi:10.3969/j.issn.1006-7795.2012.05.021

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Objective To evaluate efficacy of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification in prediction of recurrence, progression and cancer-specific mortality. Methods The dates of 384 patients who underwent transurethral resection of primary urothelial tumors were retrospectively studied. Results The difference of recurrence, progression and cancer-specific mortality rate among 6 groups was significant (P<0.05), and progression and cancer-specific mortality rate between Ta and T1 stage was significant (P<0.05). Conclusion WHO2004 pathological classification of urothelial tumors could well reflect the outcome of the patients with bladder urothelial tumors and it is useful to estimate the tumors progress.

Influence of papaverine and nitroglycerin on endothelium of left internal mammary artery

WANG Yan-jun;ZHANG Yong;WU Ming-ying;ZHOU Zi-qiang

2012, 33(5):  661-664.  doi:10.3969/j.issn.1006-7795.2012.05.022

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Objective To evaluate the effect of intraluminal injection of papaverine and nitroglycerin on endothelial function of the pedicle left internal mammary artery(LIMA) after preparation through organ bath.Methods The study comprised of 50 patients who underwent harvesting of the LIMA as a graft to the left anterior descending coronary artery in preparation for off-pump coronary bypass grafting. The LIMA was harvested by no-touch technique. The patients were randomly subdivided into two treatment groups and each had 25 patients. Three mg/3 mL heparinized autologous blood papaverine and nitroglycerin were intraluminally injected. The LIMA endothelium function was examined in isolated organ baths. Contractile function of arterial rings were obtained by using potassium (KCl 80 mmol/L) and three different concentration (10^-7 mol/L -10^-5 mol/L) of norepinephrine (NE) after intraluminal injection of these two vasodilators. Endothelium-dependent diastolic response was tested in response of 10^-7 mol/L -10^-5 mol/L acetylcholine (Ach).ResultsThe maximum contraction forces in response to 80 mmol/L KCl were not significantly different between papaverine and nitroglycerin (P=0.957); the relative vasoconstriction of papaverine and nitroglycerin after cumulative concentration of NE,10^-7mol/L (P=0.276), 10^-6 mol/L (P=0.396) and 10^-5 mol/L (P=0.554), they all showed no significant differences; endothelium dependent relaxation percentage with cumulative relaxation concentration Ach, 10^-7mol/L (P=0.299),10^-6 mol/L(P=0.163)and 10^-5 mol/L(P=0.089),was not significantly different. Conclusion The results suggest that IMA 3 mg/3 mL heparinized autologous blood papaverine and nitroglycerin as topical intraluminal vasodilators did not induce functional change of the artery.

临床研究

Detecting the expression of serum zincα -2-glycoprotein in patients with various digestive system carcinoma and its clinical significance

MENG Qian;ZHAO Xu-hong;ZHAO Jin;LEI Ting;ZHANG Man

2012, 33(5):  665-668.  doi:10.3969/j.issn.1006-7795.2012.05.023

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Objective To explore the relationship between zinc-α-glycoprotein (ZAG) and lipid metabolic state of tumor patients, the serum levels of lipolytic factor ZAG in patients with various digestive system carcinoma were detected.Methods We collected serum samples from patients with various digestive system carcinoma, benign lesions and normal subjects. For each disease and normal subject we collected 6 cases. And then we detected lipid metabolism related indexes of all samples. The serum levels of ZAG were semi-quantitative identified by using western blotting. Results In each group, the serum levels of TC, TG, HDL-C, LDL-C were no significant difference among the normal, benign and malignant groups. In gastric, colonic, rectal groups, the expression of ZAG in serum among the normal, benign and malignant groups had no obvious difference (P=0.589, P=0.618, P=0.864). However,there was a significant difference between hepatocellular carcinoma group and normal group or benign group (P=0.013, P=0.008), but between the normal group and benign group, there was no statistical significance (P=0.804). Conclusion The expression of ZAG in serum were different among various digestive system carcinoma,especially, hepatocellular carcinoma group was more significant than gastric, colonic and rectal malignant groups. Compare with TC, TG, HDL-C and LDL-C, ZAG may be a more sensitive indicator for evaluating lipid metabolism of patients with hepatocellular carcinoma.

A population-based prevalence survey and risk factor analysis of diabetic retinopathy in Beijing Changping District

YUAN Ming-xia;XIN Zhong;FENG Jian-ping;WAN Gang;SHI Jing;GENG Kun;XU Zhi-xin;ZHU Xiao-rong;MA Jing;YANG Jin-kui

2012, 33(5):  669-675.  doi:10.3969/j.issn.1006-7795.2012.05.024

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Objective This study describes the prevalence and risk factors of diabetic retinopathy (DR) in a Chinese population in Beijing Changping district. Methods In a total of 8 155 Chinese between 18~79 years of age, who participated in the 2010 Health Examination Survey in Beijing representing a population of 1 600 000 citizens in the district, 3 760 subjects whose fasting plasma glucose (FPG) ≥ 5.6 mmol/L were invited to the study and 2 551 subjects completed physical examination and laboratory measurements including FPG, oral glucose tolerance test (OGTT)-2h plasma glucose (2hPG) and hemoglobin A1c (HbA1c). The grade of DR was assessed with two 45° color digital retinal images.Results Of the 2 551 persons, 280 with known diabetes, 334 with newly-diagnosed diabetes and 853 with impaired glucose regulation (IGR) were identified. The prevalence of DR in diabetes and IGR subjects was 9.9% and 1.2%, respectively. The prevalence of retinopathy was much lower in newly-diagnosed diabetes (2.7%) than in known diabetic subjects (18.6%). In diabetic patients, independent risk factors for retinopathy were longer diabetes duration ［odds ratio (OR) 1.49=(95% CI 1.38~1.62), for every one year increase］, FPG ［OR=1.32 (95% CI 1.22~1.43), per mmol/L］, 2hPG ［OR=1.18 (95% CI 1.12~1.24), per mmol/L］, HbA1c ［OR=1.66 (95% CI 1.45~1.90), per 1%］, and higher systolic blood pressure ［OR=1.16 (95% CI 1.02~1.31), per 10 mmHg(1 mmHg=0.133 kPa)］. Conclusion The prevalence of DR in patients with diabetes and pre-diabetes was much lower in this study than that reported in western countries. The major risk factors for retinopathy are longer duration of diabetes, hyperglycemia, and hypertension.

Value of two-dimensional and color Doppler ultrasonography in diagnosis of Hashimoto's thyroiditis

DU Lan;WANG Ping

2012, 33(5):  676-681.  doi:10.3969/j.issn.1006-7795.2012.05.025

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Objective To explore the value of two-dimensional (2D) and color Doppler ultrasonography in diagnosis of Hashimoto's thyroiditis (HT) with different thyroid functions.Methods A total of 60 HT patients and 25 normal control persons were enrolled.All the patients were examined with 2D and color Doppler ultrasonography. Results 1The thickness of the lateral lobe in three HT groups were greater than those in the normal control.There was a significant difference (P<0.01) between the thicknesses of the gland in each group.The thickness of the isthmus in the HT hypothyroidism group was greater than that in the others.2The HT patients with hyperthyroidism and euthyroidism had 2D pattern Ⅰ, while the HT patients with hypothyroidism had 2D pattern Ⅱ. The prevalence of gridding hyperechoic in HT patients with hypothyroidism was significantly higher than the other groups (P<0.05). 3The HT patients with hyperthyroidism showed color Doppler flow imaging (CDFI) pattern Ⅱ and pattern Ⅲ. The HT patients with euthyroidism showed CDFI pattern 0 and pattern Ⅰ. The HT patients with hypothyroidism showed CDFI pattern Ⅰ and pattern Ⅱ. 4There was a significant difference in peak systolic velocity (PSV) of superior thyroid artery among the four groups (P<0.05). The PSV in HT patients with hyperthyroidism was obviously higher than that in HT patients with hypothyroidism and euthyroidism, and the PSV in HT patients with hypothyroidism was also higher than that in HT patients with euthyroidism. There was not any significant difference in RI in the three HT groups.Conclusion The 2D and color Doppler ultrasonography can be applied to diagnose Hashimoto's thyroiditis with different thyroid functions.

Clinical analysis of retroperitoneal laparoscopic partial nephrectomy:a report of 49 cases

LU Qing;JIANG Wei;XU En-ci;CAI Wei-zhong;ZHENG Song;CHEN Jiang-ying

2012, 33(5):  682-685.  doi:10.3969/j.issn.1006-7795.2012.05.026

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Objective To evaluate the safety and clinical efficacy of retroperitoneal laparoscopic partial nephrectomy (RLPN).MethodsForty-nine cases who underwent RLPN were analyzed retrospectively, the patients were followed up for five years. Tumors were on the left side in 23 cases and on the right in in 26. The mean tumor size was 3.9 (1.5~6.3) cm in diameter. The tumor was resected with a margin of 5 to 10 mm of healthy renal parenchyma.Results All the operations were completed successfully, without conversion to open surgery and no organ injury occurred. Mean operating time was 82 (45~130 ) min, the mean warm ischemic time was 28 (18~40) min and mean estimated blood loss was 250 (50~500) mL. The pathological studies revealed 35 cases of clear cell carcinoma, 2 cases of papillary renal cell carcinoma,9 cases of angioleiomyolipoma and 3 cases of renal oncocytoma.The surgical margin was negative in all cases.Urine leakage was found in 1 case, perinephric hematoma in 1 case, impaired renal function in 1 case, the incisions in all the cases were healed without secondary surgical invention. The mean hospital stay was 9 (7~12) d. During 4~49 months of following up, there was no recurrence of tumor. Conclusion RLPN could be a safe and minimally invasive procedure, and it is worthy of promotion for qualified hospitals.

诺贝尔奖

Cell development backwards:somatic cell nucleus transfer and induced pluripotent stem cells——introduction of Nobel Prize in Physiology or Medicine 2012

WANG Xuan;WANG Xiao-min

2012, 33(5):  689-694.  doi:10.3969/j.issn.1006-7795.2012.05.028

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The 2012 Nobel Prize in Physiology or Medicine is awarded jointly to Dr. John B. Gurdon from United Kingdom and Dr. Shinya Yamanaka from Japan for their significant discovery that mature cells can be reprogrammed to become pluripotent. Their breakthrough findings have revolutionized the traditional view on the development program of cells or organisms, leading to an exploration on cell fate reversal.

G protein coupled receptor, the vault of drug discovery——introduction of Nobel Prize in Chemistry 2012

ZHANG Chen-guang;DING Wei

2012, 33(5):  695-699.  doi:10.3969/j.issn.1006-7795.2012.05.029

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Two American scientists Robert Lefkowitz and Brian Kobilka have honored the 2012 Nobel Price in Chemistry for their achievements in the G protein coupled receptor (GPCR) studies. In this article, we introduced their research in the related fields and summarized their major academic contributions that recognized among scientific researchers. Furthermore, we expanded the discussion regarding the significance and the potential applications of their work for morden medication and drug development.