社区美沙酮维持治疗对海洛因成瘾者吸毒行为影响的初步研究

目的 了解四川省西昌市社区美沙酮维持治疗对海洛因成瘾者吸毒行为的影响情况。方法于2004—05／07，以社区为基础招募海洛因成瘾者，调查其社会人口学、毒品使用及共用注射器具行为特征，了解社区美沙酮维持治疗（MMT）对吸毒行为的影响情况。结果 在调查的海洛因成瘾者中参加过MMT的为30．4％（105／346），参加MMT时间的中位数为49d。在控制社会人口学等因素后，多因素Logistic分析结果显示，MMT与海洛因成瘾者近3个月吸毒行为的关系有统计学意义的变量为：静脉吸毒频率（OR：0．40；95％CI：0．24～0．66）、海洛因口吸频率（OR：3．06；95％CI：1．87～5．00）、海洛因混合其他毒品使用频率（OR：0．43；95％CI：0．26～0．73）、共用针头或注射器（OR：0．03；95％CI：0．01-0．13）、共用洗针头或注射器用水（OR：0．06；95％CI：0．01～0．24）和共用吸毒器皿（OR：0．02；95％CI：0．00～0．18）。结论 研究结果表明我国第一批海洛因成瘾者美沙酮维持治疗试点项目在减少吸毒人群毒品使用和艾滋病相关高危吸毒行为等方面具有明显的效果。     

大蒜素对大鼠心室肌细胞L-型钙通道的影响

目的:探讨大蒜素对大鼠心室肌细胞L-型钙通道的作用.方法:用急性酶解法获得大鼠的单个心肌细胞,用标准的全细胞膜片钳技术记录钙通道电流.结果:5、50、250和500μmol/L大蒜素分别抑制钙电流4.4%、26.91%、38.06%、72.90%.250μmol/L大蒜素能使心肌细胞钙电流-电压曲线明显上移,峰电流密度从(7.17±0.65)pA/pF减少至(4.44±0.52)pA/pF(n=15,P<0.05),但激活电位、峰电位和翻转电位无明显改变(P>0.05).大蒜素能使钙电流失活曲线明显左移(P<0.05).大蒜素对钙电流激活曲线、失活再复活曲线和频率依赖性无明显影响(P>0.05).结论:大蒜素呈浓度依赖性地抑制心肌细胞L-型钙通道.     

Constructing Large Scale Cohort for Clinical Study on Heart Failure with Electronic Health Record in Regional Healthcare Platform: Challenges and Strategies in Data Reuse

Regional healthcare platforms collect clinical data from hospitals in specific areas for the purpose of healthcare management. It is a common requirement to reuse the data for clinical research. However, we have to face challenges like the inconsistence of terminology in electronic health records (EHR) and the complexities in data quality and data formats in regional healthcare platform. In this paper, we propose methodology and process on constructing large scale cohorts which forms the basis of causality and comparative effectiveness relationship in epidemiology. We firstly constructed a Chinese terminology knowledge graph to deal with the diversity of vocabularies on regional platform. Secondly, we built special disease case repositories (i.e., heart failure repository) that utilize the graph to search the related patients and to normalize the data. Based on the requirements of the clinical research which aimed to explore the effectiveness of taking statin on 180-days readmission in patients with heart failure, we built a large-scale retrospective cohort with 29647 cases of heart failure patients from the heart failure repository. After the propensity score matching, the study group (n=6346) and the control group (n=6346) with parallel clinical characteristics were acquired. Logistic regression analysis showed that taking statins had a negative correlation with 180-days readmission in heart failure patients. This paper presents the workflow and application example of big data mining based on regional EHR data.     

G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer

BACKGROUND A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.METHODS Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.RESULTS G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1^highYWHAZ^high gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.CONCLUSIONS The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.Subject terms: Gastric cancer, Cell death     

Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E

ABSTRACT: BACKGROUND: The molecular mechanisms of dietary oils (such as fish oil) and unsaturated fatty acids, which are widely used by the public for anti-inflammation and vascular protection, have not been settled yet. In this study, prostaglandin E2 (PGE2)-mediated calcium signaling was used to screen dietary oils and eight unsaturated fatty acids for identification of their anti-inflammatory mechanisms. Isolated fat/stromal cells expressing endogenous PGE2 receptors and an HEK293 cell line specifically expressing the recombinant human PGE2 receptor subtype-1 (EP1) were cultured and used in live cell calcium signaling assays. The different dietary oils and unsaturated fatty acids were used to affect cell signaling under the specific stimulation of a pathological amount of inflammatory PGE2. RESULTS: It was identified that fish oil best inhibited the PGE2 signaling in the primary cultured stromal cells. Second, docosahexaenoic acid (DHA), found in abundance in fish oil, was identified as a key factor of inhibition of PGE2 signaling. Eicosapentaenoic acid (EPA), another major fatty acid found in fish oil and tested in this study was found to have small effect on EP1 signaling. The study suggested one of the four PGE2 subtype receptors, EP1 as the key target for the fish oil and DHA target. These findings were further confirmed by using the recombinant EP1 expressed in HEK293 cells as a target. CONCLUSION: This study demonstrated the new mechanism behind the positive effects of dietary fish oils in inhibiting inflammation originates from the rich concentration of DHA, which can directly inhibit the inflammatory EP1-mediated PGE2 receptor signaling, and that the inflammatory response stimulated by PGE2 in the fat stromal cells, which directly related to metabolic diseases, could be down regulated by fish oil and DHA. These findings also provided direct evidence to support the use of dietary oils and unsaturated fatty acids for protection against heart disease, pain, and cancer resulted from inflammatory PGE2.