Alcohol Consumption and Risk of Gastric Cancer: The Japan Collaborative Cohort Study

BackgroundAlcohol consumption is a potential risk factor for gastric cancer. However, findings from cohort studies that examined the relationship between alcohol consumption and gastric cancer risk among Japanese population are not conclusive.MethodsA total of 54,682 Japanese men and women participating in the Japan Collaborative Cohort study completed a questionnaire, including alcohol consumption information. The Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsAfter a median 13.4-year follow-up, we documented 801 men and 466 women incident cases of gastric cancer. Alcohol consumption was associated with increased risk of gastric cancer among men (HRs in ex-drinkers and current alcohol consumption of <23 g, 23–<46 g, 46–<69 g, and ≥69 g/d categories versus never drinkers were 1.82; 95% CI, 1.38–2.42, 1.41; 95% CI, 1.10–1.80, 1.47; 95% CI, 1.17–1.85, 1.88; 95% CI, 1.48–2.38, and 1.85; 95% CI, 1.35–2.53, respectively, and that for 10 g increment of alcohol consumption after excluding ex-drinkers was 1.07; 95% CI, 1.04–1.10). The association in men was observed for cardia and non-cardia gastric cancer (HRs in the highest alcohol consumption category versus never drinkers were 9.96; 95% CI, 2.22–44.67 for cardia cancer and 2.40; 95% CI, 1.64–3.52 for non-cardia cancer). However, no such trend was observed in women.ConclusionsAlcohol consumption is associated with increased risk of gastric cancer among Japanese men, regardless of anatomical subsite of the cancer.Key words: gastric cancer, alcohol, JACC study     

The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming (alpha) subunits of voltage-gated Na+ (Na(v)) channels. The neurological phenotypes seen in Fgf14-/- mice and the identification of an FGF14 missense mutation (FGF14(F145S)) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14(F145S) reduces Na(v) alpha subunit expression at the axon initial segment, attenuates Na(v) channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14(F145S) does not interact directly with Na(v) channel alpha subunits. Rather, FGF14(F145S) associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Na(v) alpha subunits, suggesting that the mutant FGF14(F145S) protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Na(v) channel alpha subunits and altering neuronal excitability.     

大豆磷脂脂质体对FeSO4／Cysteine引起培养心肌细胞损伤的保护效应

目的:观察大豆磷脂脂质体的累积对FeSO4/Cysteine体系产生羟自由基引起心肌细胞损伤的保护作用。方法:①实验于2003-10/2004-07在锦州医学院生物化学实验室完成。选用新生两三天清洁级SD大鼠的乳鼠10～15只,取心肌细胞进行原代培养48h后,随机分成3组:正常对照组、损伤组和大豆磷脂脂质体保护组。损伤组加入FeSO4/Cysteine(终浓度FeSO41×10-3mol/L Cysteine5×10-4mol/L)作用于培养的乳鼠心肌细胞12h。大豆磷脂脂质体保护组在加入损伤因素的同时加入不同质量浓度的大豆磷脂脂质体(0.2,0.4,0.8,1.6g/L)。②测定心肌细胞培养液中乳酸脱氢酶的活力,心肌细胞中丙二醛的含量和超氧化物歧化酶的活力,均参照南京建成生物工程研究所提供的试剂盒说明书进行。培养心肌细胞线粒体内琥珀酸脱氢酶的活力采用甲基四唑蓝比色测定。结果:①培养液中乳酸脱氢酶的活力:损伤组显著高于正常对照组(P<0.01)。大豆磷脂脂质体保护各组均低于损伤组(P<0.01)。②培养心肌细胞中丙二醛的含量:损伤组显著高于正常对照组(P<0.01)。大豆磷脂脂质体保护各组均低于损伤组(P<0.01)。③培养心肌细胞中超氧化物歧化酶的活力:损伤组显著低于正常对照组(P<0.01)。大豆磷脂脂质体保护各组均高于损伤组(P<0.01)。④心肌细胞线粒体内琥珀酸脱氢酶的活力:损伤组显著低于正常对照组(P<0.01)。大豆磷脂脂质体保护各组均高于损伤组(P<0.01)。⑤大豆磷脂脂质体保护作用在一定浓度范围(0.2～0.8g/L)随着浓度的升高而增强,但剂量达到一定浓度,大豆磷脂脂质体保护作用不再随着浓度的升高而增强。结论:大豆磷脂脂质体对FeSO4/Cysteine体系产生的羟自由基引起的心肌细胞损伤具有明显的保护作用,且存在大豆磷脂脂质体浓度依赖性。     

胶原-生物衍生骨材料与兔成骨细胞的相容性及其体外附着特点

目的:观察胶原-生物衍生骨复合材料与兔成骨细胞的相容性及体外附着规律,为进一步的体内实验提供参考数据。方法:实验于2003-10/2005-02在华西医科大学组织工程实验室进行。①材料制备:新鲜捐献骨(人),经脱脂、脱蛋白等工艺制成单纯生物衍生骨材料,以Ⅰ型胶原通过真空吸附法修饰单纯生物衍生骨材料表面,构建出胶原生物衍生骨材料。②实验方法:将体外培养的兔骨膜成骨细胞分别复合于单纯生物衍生骨材料和胶原生物衍生骨材料,共同培养7d。③观察指标:分别于培养第1,3,5和7天取材,扫描电镜观察成骨细胞形态及附着情况;用紫外/荧光/可见光高效分析仪测定成骨细胞产生的碱性磷酸酶活性;MTT检测成骨细胞增殖情况;用流式细胞仪检测兔成骨细胞的细胞周期、DNA含量及倍体水平。结果:①扫描电镜结果:胶原生物衍生骨材料组成骨细胞黏附和增殖优于生物衍生骨材料组。②碱性磷酸酶活性:生物衍生骨材料组低于胶原生物衍生骨材料组(0.019±0.003,0.038±0.004,P<0.05)。③细胞增殖情况:在培养第1,3,5,7天胶原生物衍生骨材料组成骨细胞A值均高于生物衍生骨材料组(P<0.05)。④流式细胞检测生物衍生骨材料、胶原生物衍生骨材料对兔成骨细胞的细胞周期影响不大,各组细胞皆为正常的二倍体细胞,未见异倍体细胞形成,胶原修饰后无细胞毒性。结论:以单纯生物衍生骨作为载体,其表面经胶原修饰后的复合材料与成骨细胞有良好的细胞相容性,无细胞毒性。     

上海农村社区中老年人群2型糖尿病危险因素的调查:巢式病例-对照

目的:采用1∶2频数匹配,病例-对照设计,分析上海市农村社区中老年人群2型糖尿病的危险因素。方法:①于2003年和2005年,以整群抽样的方法,抽取上海市奉贤区光明镇和钱桥镇40～85岁常住人口共计10582人,合并建立卒中队列研究人群。选择其中199例2型糖尿病患者为病例组,根据其年龄、性别分布情况,以1∶2的比例从上述同一人群中选取398例非糖尿病患者为对照组。②根据知情同意原则,应用自行设计统一的调查表格进行基线调查,并接受无创性的脑血管功能检测。调查内容包括一般人口学特征、卒中常见危险因素(高血压、冠心病、糖尿病、高脂血症、家族遗传史等),当场测量身高、体质量、血压水平,计算脑血管血液动力学指标积分,分值0～100分,分值越低,脑血管功能异常越严重。③率或构成比的比较用χ2检验,均数的比较用t检验或方差分析,单因素分析主要评价指标为优势比(OR),多因素分析用非条件logistic回归方程。结果:①单因素分析显示,高血压、冠心病、高脂血症、超重或肥胖、糖尿病家族史、吸烟、饮酒、脑血管血液动力学积分异常的均为糖尿病发病的影响因素[OR(95%CI)分别为2.90(1.98,4.23),2.08(1.16,3.74),3.40(1.53,7.62),1.58(1.05,2.39),6.16(2.97,13.01),1.51(1.02,2.23),0.48(0.27,0.86),2.44(1.69,3.51),P<0.05～0.01]。②多因素分析提示,糖尿病家族史、高血压、高脂血症是2型糖尿病的独立危险因素(Exp(B)分别为8.840,1.777,1.833,P<0.01),脑血管血液动力学积分异常与2型糖尿病有关(Exp(B)为1.010,P<0.05)。结论:2型糖尿病的主要致病危险因素是高血压、高脂血症和糖尿病家族史。     

Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: A double-blind placebo-controlled trial

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients’ feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.     

Erythropoietin stimulates a rise in intracellular-free calcium concentration in single BFU-E derived erythroblasts at specific stages of differentiation

Human cord blood progenitor-derived erythroblasts have recently been shown to respond to erythropoietin (Epo) or granulocyte-macrophage colony-stimulating factor (GM-CSF) with a transient increase in intracellular free calcium concentration [Cac]. However, the importance of [Cac] changes in mediating cell proliferation and/or differentiation is undefined. In the present study, the response of erythroid precursors at different stages of differentiation to Epo was examined. Erythroblasts were derived from adult blood erythroid progenitors (BFU- E) at day 7 or day 10 of culture. [Cac] was measured in individual Fura- 2 loaded cells with fluorescence microscopy coupled digital video imaging. The dynamic range (Rmax/Rmin) of intracellular Fura-2 was similar to that measured in free solution, suggesting insignificant amounts of intracellular Ca insensitive forms of Fura-2. Baseline [Cac] of erythroid cells calculated with an in vitro calibration method was 44 +/- 4 nmol/L and with an in vivo method was 46 +/- 4 nmol/L. Treatment of day 7 BFU-E derived erythroblasts with Epo resulted in no significant increase in [Cac]. In contrast, in more mature erythroblasts (day 10 of culture), Epo stimulated a large increase in [Cac] from 49 +/- 11 nmol/L at baseline to 279 +/- 47 nmol/L. This [Cac] increase occurred in phosphate buffered saline (PBS) containing no added calcium. The increase in [Cac] persisted for 18 minutes and was dose dependent. Day 7 and day 10 control cells treated with either insulin or media showed no significant change in [Cac] during 18 minutes of observation. Our data demonstrate that early (day 7) and late (day 10) erythroblasts display different responses to Epo, at least in terms of intracellular Ca++ fluxes. The differential [Cac] response observed in early and late erythroid precursors to growth factor stimulation suggests that [Cac] may be an important signal in cell differentiation.