结肠癌患者粪便胆汁酸和短链脂肪酸的变化及其意义

目的 探讨结肠癌患者粪便胆汁酸和短链脂肪酸水平的变化及意义。方法 收集189例结肠癌、201例腺瘤性息肉患者和512例经肠镜检查结果正常者的粪便标本,采用酶联免疫吸附法检测3组研究对象粪便胆汁酸及短链脂肪酸的浓度。结果 总胆汁酸、初级胆汁酸和次级胆汁酸在正常对照组、腺瘤性息肉组、结肠癌组差异均无统计学意义(P均＞0.05)。结肠癌组的鹅脱氧胆酸［0.338（0.101,0.416） mg/g］高于腺瘤性息肉组［0.241（0.108,0.375） mg/g］和正常对照组［0.248（0.110,0.371） mg/g］(P＝0.025,P＝0.023),而腺瘤性息肉组和正常对照组差异无统计学意义(P＞0.05)。结肠癌组和腺瘤性息肉组的脱氧胆酸［0.375（0.136,0.503） mg/g与0.369（0.113,0.494）mg/g］高于正常对照组［0.277（0.115,0.412）mg/g］(P＝0.026,P＝0.024),而结肠癌组和腺瘤性息肉组差异无统计学意义(P＞0.05)。结肠癌组的石胆酸［0.386（0.147,0.507）mg/g］高于腺瘤性息肉组［0.103（0.012,0.238）mg/g］和正常对照组［0.239（0.081,0.405）mg/g］（P＝0.011,P＝0.027）,而腺瘤性息肉组低于正常对照组(P＝0.022)。总的短链脂肪酸、乙酸、丙酸和异戊酸在正常对照组、腺瘤性息肉组、结肠癌组差异均无统计学意义(P均＞0.05)。结肠癌组和腺瘤性息肉组的丁酸［0.105(0.059,0.198)mg/g与0.090(0.050,0.183)mg/g］、异丁酸［0.036(0.024,0.046)mg/g与0.025(0.020,0.034)mg/g］高于正常对照组［0.081(0.051,0.107)mg/g与0.021(0.016,0.029)mg/g］（丁酸：P＝0.026,P＝0.021;异丁酸：P＝0.025,P＝0.029）,且结肠癌组高于腺瘤性息肉组,差异均有统计学意义(丁酸：P＝0.031;异丁酸：P＝0.024）)。结论 粪便中鹅脱氧胆酸、石胆酸和丁酸、异丁酸可能与结肠癌的发生有关,同时脱氧胆酸可能与结肠癌和结肠腺瘤均存在联系,而胆汁酸和短链脂肪酸的其他成分与结肠癌和腺瘤无关。     

Properties of folic acid gamma-glutamyl hydrolase (conjugase) in rat bile and plasma

The properties of folic acid gamma-glutamyl hydrolase (conjugase) [EC 3.4.12.10] in rat bile and plasma were investigated. Conjugase activity in bile showed two pH optima; one at pH 4.5-5.0 and one at pH 6.7-7.5. The enzyme activity in plasma had a broad pH--profile with an optimum at pH 6.2-7.5. Conjugase activity from both bile and plasma was inhibited in the presence of the sulfhydryl reagent, p-hydroxymercuriphenylsulfonate, and stimulated in the presence of 2-mercaptoethanol. Conjugase activity in bile was inhibited by Zn2+ at pH 7.5 but not at pH 4.5 and was much more stable to heat at pH 4.5. No separation of the biliary conjugase activity measured at the two different pH values was obtained by Sephadex G-150 chromatography. Secretion of biliary conjugase was essentially constant over a 6-hour period when activity was assayed at pH 4.5 or pH 7.5. The enzyme in bile converted pteroyltriglutamate to a mixture of about 5% glutamate an 95% gamma-glutamylglutamate at either pH, whereas the enzyme in plasma produced 23% glutamate and 77% gamma-glutamylglutamate. The possible contribution of biliary conjugase to intestinal absorption of folate polyglutamates is discussed.     

Mucor divergence in aflatoxin effects with duckling bile and plasma

Aflatoxin effects on duckling growth and rates of changes in liver, bile, and plasma components during 10-day bioassay periods were determined with the WHO/FAO/UNICEF-defined 60% peanutmeal diet. Aflatoxin at 1.578 μg/g feed (0.948 μg B₁ and 0.630 μg G₁ (depressed growth 78%, reduced feed conversion efficiency 60%, increased liver size 42%, and reduced bile riboflavin 94%. The toxin induced reduction in blood plasma levels for flavin monophosphate 76%, cholesterol 26%, total lipids 79%, and lipase 74%. Riboflavin, pantothenol, and Mucor extract amendments with aflatoxin level of 0.988 μg/g feed (0.593 μg B₁ and 0.395 μg G₁) induced significant changes in aflatoxin effects with the Mucor extract resulting in near normal bile, plasma, and liver characteristics with minimal hepatic cellular aberrations.     

Bioavailability of food folates and evaluation of food matrix effects with a rat bioassay

Folate bioavailability of beef liver, lima beans, peas, spinach, mushrooms, collards, orange juice and wheat germ was estimated with a protocol of folate depletion-repletion using growth and liver, serum and erythrocyte folate of weanling male rats. Diets with 125, 250 and 375 micrograms folic acid/kg were standards. Individual foods were incorporated into a folate-free amino acid-based diet alone (250 micrograms folate/kg diet from food) or mixed with folic acid (125 micrograms folate from food + 125 micrograms folic acid) to evaluate folate bioavailability and effects of food matrix. Beef liver and orange juice folates were as available as folic acid, whereas those of wheat germ were less bioavailable. Folates of peas and spinach were also less available than folic acid using liver and serum folate concentrations and total liver folate as response criteria, but they were not lower when based on growth and erythrocyte folate concentrations. Lima bean, mushroom and collard folates were as available as folic acid using four of five response criteria. Folate bioavailability of all foods generally exceeded 70%. All response criteria gave approximately equivalent results, indicating that growth and tissue folate levels are appropriate criteria. No food matrix effects were observed for any food except lima beans. Foods rich in polyglutamyl folates were less bioavailable than those of foods rich in short-chain folates.     

肺癌组织中的8-OH-dG及其与几种癌变相关基因的关系

为探讨 8 羟基 脱氧鸟苷 (8 OH dG)与人群肺癌发生及癌变相关基因的关系 ,使用针对 8 OH dG加合物的鼠抗人单克隆抗体 ,通过免疫学方法检测 1 50例肺癌、1 2 0例癌旁肺组织、40例肺良性病变和 40例正常肺组织中氧化损伤标志物 8 OH dG的含量 ;同时检测相应肺组织中P53、C MYC、K RAS、BCL 2、hTERT等癌变相关基因的表达 ,分析 8 OH dG与上述癌变相关基因表达的关系。结果显示 ,92 7% (1 39 1 50 )的肺癌组织中可检出氧化损伤标志物 8 OH dG ,其阳性标志细胞的比率为 (2 4 0 0± 2 5 1 1 ) % ;1 7 5 % (2 1 1 2 0 )的癌旁肺组织可检出 8 OH dG ,阳性标志细胞的比率为 (2 42± 5 98) % ;1 0 0 % (4 40 )的肺良性病变组织可检出 8 OH dG ,阳性标志细胞的比率为 (0 80± 1 30 ) % ;5 0 % (2 40 )的正常肺组织可检出 8 OH dG加合物 ,阳性标志细胞的比率为 (0 34± 1 0 1 ) % ,肺癌中 8 OH dG的含量高于其它肺组织 (P <0 0 1 )。将肺癌病例按性别、年龄、细胞类型和吸烟史分层 ,它们皆与 8 OH dG无关联。分析 8 OH dG与癌变相关基因的关系 ,发现肺癌组织K RAS、BCL 2基因阳性表达者 8 OH dG的含量高于上述基因阴性表达者 ,P值分别为 0 0 35和 0 0 34 ;而P53、C MYC和hTERT基因表达与 8 OH dG的含     

Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer

Over the past two decades, bioactive natural compounds have been shown to be a plausible adjunct to the treatment of breast cancer, the second leading cause of cancer death among American women. This study was designed to investigate the effects of ursolic acid (UA), a pentacyclic triterpene found in many foods and herbs, in a model of postmenopausal breast cancer. Ovariectomized C57BL/6 mice (n = 40) were randomized to receive control diet (AIN-93G) or diet supplemented with UA at 1 of 3 doses (wt/wt): 0.05%, 0.10%, or 0.25% (≈54, 106, or 266 mg/kg body weight/day, respectively). After 3 wk, syngeneic MMTV-Wnt-1 mammary tumor cells were injected in the mammary fat pad, and mice continued on their respective diets for 5 more wk. All UA doses decreased tumor cell proliferation, as assessed by Ki67 immunostaining; nevertheless, UA at 0.10% was most effective in inhibiting tumor take and decreasing tumor final tumor size. Modulation of Akt/mTOR signaling and induction of apoptosis appeared to mediate these effects on tumor growth. UA potently disrupted cell cycle progression and induced necrosis in a clonal MMTV-Wnt-1 mammary tumor cell line in vitro. This study supports the potential of UA as an antitumorigenic agent.     

HDCP患者血浆HCY和PTM水平变化及其相关性

目的 检测妊娠期高血压疾病患者血浆同型半胱氨酸和血栓调节蛋白水平,探讨同型半胱胺酸和血栓调节蛋白与妊娠期高血压疾病的关系,及同型半胱胺酸与血栓调节蛋白的相关性.方法 采用酶联免疫吸附试验分别检测各组患者血浆同型半胱胺酸和血栓调节蛋白水平,与正常晚孕妇女和正常非孕妇女各30名进行比较,并进行相关性分析.结果 正常晚孕组血浆同型半胱胺酸(11.75±3.77)和血栓调节蛋白(24.83±9.51)水平高于正常非孕组(8.18±2.51和18.49±8.46),差异有显著性(P＜0.01).轻度妊娠期高血压疾病组患者血浆同型半胱胺酸(13.89±4.23)和血栓调节蛋白(30.06±9.79)水平与正常晚孕组差异无显著性(P＞0.05);中、重度组患者血浆同型半胱胺酸(21.26±5.14)和血栓调节蛋白(43.27±16.15)水平明显高于轻度组患者和正常晚孕组,差异均有显著性(P＜0.01).血浆同型半胱胺酸水平与血栓调节蛋白水平呈显著的正相关(r=0.628、t=6.605、P＜0.01).结论 妊娠期高血压疾病患者血浆同型半胱胺酸及血栓调节蛋白水平均较正常孕妇明显升高,且与患者病情正相关.高同型半胱胺酸血症可能与妊娠期高血压疾病内皮细胞损伤有关,高浓度血栓调节蛋白是血管内皮细胞受损或功能活化标志,血浆同型半胱胺酸水平与血栓调节蛋白水平具有相关一致性.     

轻中度高血压人群叶酸与同型半胱氨酸水平的相关分析

目的探讨轻中度高血压患者血清叶酸水平与血浆总同型半胱氨酸水平（tHcy）的相关性。方法从哈尔滨、沈阳、北京、西安、上海和南京六城市分析455位28～75岁轻中度原发性高血压患者，测定血清叶酸和血浆同型半胱氨酸水平。结果叶酸水平低于15nmol／L时，叶酸水平越低，tHcy水平越高，高tHcy血症的发生率也越高。结论轻中度高血压患者中，血清叶酸水平与血浆tHcy水平呈负相关。     

纽纯素在结肠癌病人术后肠内营养支持中的应用

目的 :用纽纯素 (Nutren)作为肠内营养制剂 ,对结肠癌病人术后进行肠内营养治疗。　方法 :6 0例结肠癌病人 ,平均年龄 (5 2 .5 3± 13 .0 4)岁 ,随机分为肠内营养纽纯素组 (EN)和静脉营养对照组 (PN) ,每组 30人。按体重每天供给热能 12 5kJ(30kcal) /kg和蛋白质 1.2 5 g/kg(0 .2 g氮 /kg) ,热氮比值为非蛋白热能 6 2 7.6kJ(15 0kcal)∶1g氮。　 结果 :EN组未见有恶心、呕吐、腹胀、腹泻等胃肠反应。全部病人的切口均Ⅰ期愈合。体重、握力、上臂围(MAC)、上臂肌围 (MAMC)、肱三头肌皮褶厚度 (TSF)、外周血淋巴细胞总数、血红蛋白 (Hb)、总蛋白 (TP)、白蛋白(A)、尿素氮 (BUN)、肌酐 (Cr)、钠 (Na)、钾 (K)、氯 (Cl)、血糖、胆固醇 (Tch)、甘油三酯 (TG)等指标均在正常范围内。EN组血清谷氨酰胺和谷氨酸水平高于PN组 ,有显著差异 (P <0 .0 5 ) ,其余氨基酸无差异。PN组尿乳果糖 /甘露醇比率 (L/M)升高 ,与EN组相比 ,有显著差异 (P <0 .0 5 )。　结论 :纽纯素对术后结肠癌病人有明显的营养治疗效果和维护肠粘膜通透性的作用。     

结直肠癌患者血浆中的miR-106a表达及其与预后的关系

目的:探讨血浆miR-106a水平与结直肠癌(CRC)患者预后生存的相关性。方法:收集60例健康体检志愿者(对照组),103例就诊我院的CRC患者(病例组),对所有人均进行血浆miR-106a实时荧光定量聚合酶链反应(real time-PCR)检测,同时采用Kaplan-Meier进行生存分析。结果:①血浆miR-106a在CRC组较对照组表达明显升高(P=0.004),与是否发生淋巴结转移有关(P=0.033);且患者术后miR-106a明显降低(P<0.001)。②对入院时CRC患者根据miR-106a相对值进行分组,miR-106a高值组术后3年内癌复发率高于低值组(P<0.001);K-M分析则显示高值组术后3年生存率低于低值组(P=0.003)。结论:血浆miR-106a的测定有助于CRC的诊断,且与CRC的复发转移有一定关系。     

Acute effects of dietary fat composition on postprandial plasma bile acid and cholecystokinin concentrations in healthy premenopausal women

Bile acids derived from intestinal bacterial metabolism and transported to the breast in plasma may influence risk of breast cancer. The purpose of the present study was to test the hypothesis that fatty acid chain length and degree of unsaturation differ with regard to their influence on the postprandial release of cholecystokinin (CCK) and the subsequent increase in plasma bile acid concentrations that occur following a meal. A randomized crossover design was used to compare five high-fat test meals (50 g fat) with a low-fat test meal (15 g) on plasma bile acid and CCK concentrations in eighteen healthy premenopausal women. The high-fat meals were enriched in oleate or palmitate, or linoleate or medium-chain triacylglycerols (MCT) or a blend of oleate and long-chain n-3 fatty acids. The postprandial increase in plasma CCK concentration was lower on the MCT meal compared with all meals and was greater following the linoleate compared with the low-fat meal. Plasma bile acid concentrations increased 2-3-fold postprandially but the increase was lower following the MCT meal compared with the other meals and was greater on the linoleate meal compared with the low-fat meal. The postprandial increases in plasma chenodeoxycholic acid concentration showed a trend to rise with increasing unsaturation of the test meal. In conclusion, meals rich in linoleate are a potent stimulus for CCK release and lead to prolonged elevations of plasma bile acids and meals containing MCT inhibit CCK release and the subsequent increase in plasma bile acid concentrations.     

Monitoring and evaluation of side effects of chemotherapy in patients with colon cancer

This study aimed to monitor and evaluate the occurrence and intensity level of nausea, vomiting and diarrhea in patients with colon cancer, submitted to outpatient chemotherapy, who received nursing information for handling these symptoms. Study participants were 17 patients, who were treated with 5-Fluorouracil and low doses of folinic acid, at the Adult Outpatient Chemotherapy Clinic of the Hospital S?o Paulo/Federal University of S?o Paulo, Brazil. Instruments were elaborated for registering these symptoms' occurrence and intensity level and a patient guide for handling them. The information and patient monitoring were carried out by the nurse during the consultations. The results showed that most of the patients (82.4%) displayed at least one of the signs and symptoms under study between the first and the 21st day of the treatment cycle. Nausea was the most frequent symptom (76.5%), with a peak on the 4th and 5th day of the cycle, followed by diarrhea (70.5%), with a peak on the 7th day, and vomiting (53.0%), with a peak on the 5th day. Regarding the intensity of these symptoms, most patients were classified as level 1, which was established as acceptable for this study. These results indicate that the nursing instructions and the continuous monitoring contributed to the effectiveness of the patient's symptom management.     

Variable effects of iron status on the concentration of ferritin in rat plasma, liver, and spleen

The present studies were conducted to determine the relationships between iron status and ferritin levels in plasma, liver, and spleen of rats. Rats were fed either iron-adequate or iron-deficient purified diets, and measurements of hemoglobin and plasma and tissue ferritin levels were made at various times during iron depletion and iron repletion. Although mean plasma ferritin concentrations of iron-deficient rats were directionally less than those of iron-adequate rats, these differences were not statistically significant due to high variability among similarly treated animals. During iron repletion plasma ferritin concentrations again were so variable that no significant effect of iron repletion on plasma ferritin concentrations was observed. On the other hand, liver and spleen ferritin concentrations of similarly treated rats were much less variable. Ferritin liver and spleen stores decreased more rapidly than hemoglobin during iron deficiency and were restored more slowly than hemoglobin during iron repletion. There was no evidence of correlation between liver and plasma ferritin concentration. Because of the variable responses of plasma ferritin concentration to iron depletion and repletion and the lack of relationship between plasma and liver ferritin concentrations, it is concluded that plasma ferritin concentration is not a good indicator of iron status in rats.     

结肠癌患者术后肠内营养治疗

目的采用肠内营养对结肠癌患术后进行营养治疗。     

Effects of saponins on bile acids and plasma lipids in the rat.

1. The effects of feeding isolated saponins on plasma lipid concentrations and on concentrations of biliary and faecal bile acids and neutral sterols were studied in the rat. 2. The animals were given one of four diets, i.e. a standard low-cholesterol synthetic diet, the diet + 10 g saponins/kg, the diet + 10 g cholesterol/kg, the diet + 10 g cholesterol + 10 g saponins/kg. 3. Saponins partially reversed the hypercholesterolaemia caused by the high-cholesterol diet and increased both the rate of bile acid secretion and the faecal excretion of bile acids and neutral sterols. The proportionate contribution of the primary bile acids (particularly chenodeoxycholic) to faecal excretion was also increased by saponins. 4. The results are discussed in relation to the hypothesis that saponins act by inducing the adsorption of bile acids by dietary fibre.     

Construction and validation of a prognostic model across several studies, with an application in superficial bladder cancer

Many models for clinical prediction (prognosis or diagnosis) are published in the medical literature every year but few such models find their way into clinical practice. The reason may be that since in most cases models have not been validated in independent data, they lack generality and/or credibility. In this paper we consider the situation in which several compatible, independent data sets relating to a given disease with a time-to-event endpoint are available for analysis. The aim is to construct and evaluate a single prognostic model. Building a multivariable model from the available prognostic factors is accomplished within the Cox proportional hazards framework, stratifying by study. Non-linear relationships with continuous predictors are modelled by using fractional polynomials. To assess the discrimination or separation of a survival model, we use the D statistic of Royston and Sauerbrei. D may be interpreted as the separation (log hazard ratio) between the survival distributions for two independent prognostic groups. To evaluate the generality of a prognostic model across the data sets, we propose 'internal-external cross-validation' on D: each study is omitted in turn, the model parameters are estimated from the remaining studies and D is evaluated in the omitted study. Because the linear predictor of a survival model tells only part of the story, we also suggest a method for investigating heterogeneity in the baseline distribution function across studies which involves fitting completely specified, flexible parametric survival models (Royston and Parmar). Our final models combine the prognostic index (obtained with stratification by study) with the pooled baseline survival distribution (estimated parametrically). By applying this methodology, we construct two prognostic scores in superficial bladder cancer. The simpler of the two scores is more suited to clinical application. We show that a three-group prognostic classification scheme based on either score produces well-separated survival curves for each of the data sets, despite identifiable heterogeneity among the baseline distribution functions and to a lesser extent among the prognostic indexes for the individual studies.