白蛋白与纤维蛋白原比值与乳腺癌患者总生存期的关系CSCD

目的探讨白蛋白与纤维蛋白原比值(albumin to fibrinogen ratio,AFR)与乳腺浸润性导管癌患者总生存期的关系。方法收集2009年1月—2012年4月河北医科大学第四医院乳腺中心收治的230例乳腺浸润性导管癌患者血液及临床资料,回顾性分析患者术前临床资料,计算AFR,Kaplan-Meier法及Cox比例回归风险模型进行生存分析,采用二分类方式,分为AFR<13.1与AFR≥13.1两组,采用单因素及多因素分析其与患者的生存关系,并建立预后模型。结果AFR≥13.1时患者生存率降低,AFR是改善总生存期(OS)的独立预后因素,将多因素分析里P<0.05的变量,即将AFR、白细胞(WBC)、雌激素受体(ER)孕激素受体(PR)、TNM分期、核分级、p53及脉管瘤栓7个指标建立OS预测模型,其受试者工作特征曲线(ROC)面积为0.882。结论AFR低表达是改善乳腺癌OS的独立预后因素,AFR、WBC、ER或PR、TNM、核分级、p53及脉管瘤栓7个指标建立OS预测模型,具有很好预测乳腺浸润性导管癌患者生存率的作用。     

术前白蛋白与纤维蛋白原比值对非肌层浸润性膀胱癌患者预后的价值

目的:探讨术前白蛋白与纤维蛋白原比值（AFR）与非肌层浸润性膀胱癌患者预后的关系。方法:回顾性分析于我院行经尿道膀胱肿瘤切除术的205名非肌层浸润性膀胱癌患者的临床资料,根据受试者工作曲线确定AFR最佳临界值为12.127,并将患者分为高AFR组（n=136）和低AFR组（n=69）。并分析AFR水平与膀胱癌患者临床资料及预后的关系。构建患者术后无复发列线图,并利用Bootstrap法计算一致性指数（C指数）以及校准曲线对其预测精准度及一致性进行验证。结果:低AFR组患者具有更高的糖尿病患病率、更大的肿瘤体积、更多肿瘤数量以及更差的组织学分级（P<0.05）。低AFR组患者的无复发生存时间较高AFR组明显缩短。COX多因素分析提示肿瘤分化程度（HR=0.530,95%CI:0.314~0.895,P=0.017）及AFR<12.127（HR=0.275,95%CI:0.161~0.471,P<0.001）是影响患者术后复发的独立危险因素。结论:AFR是非肌层浸润性膀胱癌患者的预后不良因素,对预后有一定预测价值。     

术前白蛋白与纤维蛋白原比值对三阴性乳腺癌患者的预后影响和临床意义

目的:探讨术前白蛋白与纤维蛋白原比值（albumin to fibrinogen,AFR）对三阴性乳腺癌患者的预后影响和临床意义。方法:回顾性分析我院自2010年1月至2013年12月间就诊的195例三阴性乳腺癌患者。用受试者工作特性曲线（ROC）确定AFR的最佳临界值。采用卡方检验或Fisher精确检验分析比较计数资料。Kaplan-Meier方法和Log rank方法用于分析生存曲线。单因素和多因素分析（Cox比例风险回归模型）用于评估独立的预后因素。结果:ROC曲线确定AFR最佳临界值为15.00，依此分两组，即低AFR组（AFR＜15.00）和高AFR组（AFR≥15.00）。单因素和多因素分析显示AFR是三阴性乳腺癌DFS（P=0.045，HR:0.627，95%CI:0.397~0.990；P=0.026，HR:0.595，95%CI:0.377~0.940）和OS（P=0.039，HR:0.238，95%CI:0.061~0.927；P=0.001，HR:0.385，95%CI:0.221~0.670）的独立预后因素。高AFR组患者术后中位DFS和OS显著高于低AFR组患者，差异具有显著统计学意义（χ2=8.190，P=0.004；χ2=8.720，P=0.003）。散点图分析显示，AFR与ALB呈显著正相关（R2=0.028，P=0.020），AFR与FIB呈显著负相关（R2=0.516，P＜0.000 1）。此外，对伴有淋巴管侵犯的患者，高AFR组患者比低AFR组患者术后生存时间长，预后更好。结论:术前AFR是影响患者预后的独立因素。AFR具有操作简单、易于推广、成本低、可重复性好等优点，具有潜在的临床应用价值。     

白蛋白与纤维蛋白原的比值预测弥漫大B细胞淋巴瘤患者预后的价值

目的:探讨血清白蛋白（albumin，ALB）与血浆纤维蛋白原（fibrinogen，FIB）的比值（ALB to FIB ratio，AFR）对弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma，DLBCL)患者预后的影响。方法:选择我院2015-04-17至2022-03-18确诊的DLBCL病例59例，收集所有患者首次化疗前1周内的血清ALB值、血浆FIB值，计算出AFR。应用生存分析研究AFR对DLBCL患者无进展生存率(progression free survival，PFS)的影响。应用受试者工作特征曲线(receiver operating characteristic curve,ROC)下的面积（area under the ROC curve,AUC）来评估各模型对DLBCL患者预后预测能力的大小。结果:AFR范围3.87～20.13，中位数11.16。AFR与IPI、Ann Arbor分期、结外侵犯数以及B症状密切相关。Kaplan-Meier生存分析提示，AFR增高时，DLBCL患者的PFS显著提高（P＜0.001），2年累积PFS与低AFR组患者相比提高了73.0%。Cox单因素分析提示，低AFR的DLBCL患者发生肿瘤进展或死亡的风险显著增加（P=0.002）；多因素分析提示，AFR是影响DLBCL患者PFS的独立因素（P=0.004）。国际预后指数（international prognostic index，IPI）和IPI联合AFR两种模型判断DLBCL患者PFS的AUC值分别为0.778（95%CI 0.659～0.897,P＜0.001）和0.829（95%CI 0.723～0.935,P＜0.001）。结论:AFR是判断DLBCL患者PFS的独立预测因子，IPI联合AFR能够更好地判断DLBCL患者的预后。     

治疗前白蛋白与纤维蛋白原比值对根治性放化疗宫颈癌患者预后的价值

目的：探讨治疗前白蛋白与纤维蛋白原比值（albumin-to-fibrinogen ratio,AFR）在根治性放化疗宫颈癌患者预后中的价值。方法：收集2011年1月至2018年12月于四川省肿瘤医院行根治性放化疗的241名宫颈鳞癌患者的资料,评估AFR在不同FIGO分期和生存状态组别的差异,根据受试者ROC曲线确定AFR最佳截断值,根据最佳截断值将患者分为高AFR组和低AFR组,比较两组间总生存期（overall survival,OS）和无进展生存期（progression-free survival,PFS）。结果：AFR的水平在不同的FIGO分期存在显著差异,其水平随FIGO分期的增加而下降。高AFR组患者具有更长的PFS和OS(P <0.05)。在单个指标OS诊断ROC曲线中,血小板淋巴细胞比值（platelet-to-lymphocyte ratio,PLR）的AUC最大,为0.894。单个指标PFS诊断ROC曲线中,中性粒细胞与淋巴细胞比值（neutrophil-to-lymphocyte ratio,NLR）的AUC最大,为0.867,AFR的AUC分别为0.78...     

9种化肥对蚕豆根尖细胞微核率的影响

使用微核试验法研究了９种化肥对蚕豆根尖细胞微核率的影响，结果表明上述化肥均没有引起微核率的显著升高，提示化肥既不是诱变剂也不是纺丝毒剂或非整倍体毒剂，并对相关问题进行了讨论。     

外周血甲胎蛋白mRNA的检测及其临床意义

目的：寻找肝细胞癌微小转移的标志物。方法：用巢式反转录聚合酶链反应（Nested-RT-PCR）技术检测６５例肝细胞癌,２１例非肝癌的恶性肿瘤,22例慢性乙型肝炎或肝硬化患者及21例健康志愿者外周静脉血中的甲胎蛋白（AFP）mRNA,结果：AFR－mRNA在健康志愿者,非肝癌恶性肿瘤患者外周血中均为阴性,在肝细胞癌组外周血中AFR－mRNA的检出率（44／65,67．7％）明显高于慢性乙型肝炎或肝硬化组（2／22,9．1％,P＜0．01）。AFR－mRNA检出率与临床分期、门静脉癌栓、肝外转移显著相关。在12例血清AFP＜25μg/L的肝癌患者血中,7例（58．3％）可检出AFR－mRNA.结论：AFR－mRNA可作为血循环中有肝癌细胞或肝细胞的标志物,在肝癌患者,阳性预示有血源性转移的可能,并且AFR－mRNA对血清AFP阴性或低值的肝癌患者能起到补充诊断作用。     

血清AFR、FPR及NLR与早期结直肠癌患者术后辅助化疗疗效及预后的关系

目的 探讨血清白蛋白/纤维蛋白原比值(AFR)、纤维蛋白原/前白蛋白比值(FPR)及中性粒细胞计数与淋巴细胞计数比值(NLR)与早期结直肠癌患者术后辅助化疗疗效及预后的关系。方法 选取结直肠癌患者95例，治疗后根据临床疗效分为有效组和无效组，比较2组患者年龄、临床分期、组织学分型、肿瘤部位、AFR、FPR、NLR、淋巴结转移、肿瘤大小、分化程度等资料。再根据随访预后情况将有效组患者分为疾病进展组和疾病未进展组，比较2组患者不同病理资料。结果 患者经手术辅助化疗后，CR 56例，PR 22例，SD 15例，PD 2例，其中有效共78例(82.1%)。有效组与无效组患者年龄、临床分期、AFR、FPR、NLR、淋巴结转移、分化程度差异均具有统计学意义(P<0.05)。患者年龄、临床分期、AFR、FPR、NLR、淋巴结转移、分化程度是早期结直肠癌术后辅助化疗临床疗效的影响因素。随访18个月，有效组患者中疾病进展患者24例(30.8%),疾病进展组与疾病未进展组患者在年龄、临床分期、AFR、FPR、NLR、淋巴结转移、肿瘤大小、分化程度方面的差异均具有统计学意义(P<0.05)。患者...     

通过测定微核面积和DNA含量来检出非整倍体毒剂的应用

1980年Yamamoto等首先报道了对7种染色体断裂剂和4种纺锤体毒剂诱导的小鼠骨髓红细胞MN直径的测定结果。他们用照片放大与显微尺测定结合,把MN直径大于1/4胞浆直径者定为大MN,结果发现断裂剂组大MN只有0～2.5%,而纺锤体毒剂组高达44%～47%,MN直径断裂剂组多在1μm内,纺锤体毒剂组多在1～4μm内。两类毒剂差异非常显著。     

微核形态用于区分非整倍体毒剂和染色体断裂剂的研究①

目的:通过比较非整倍体毒剂和染色体断裂剂诱导的各种微核形态类别的差异,探讨以微核形态指标区分两类诱变剂的可能性.方法:对6种标准诱变剂(非整倍体毒剂:秋水仙碱,长春新碱;染色体断裂剂:环磷酰胺,丝裂霉素C,乙基磺酸甲酯,7射线)诱导的小鼠骨髓红细胞微核,进行形态学分类分析.结果:①非整倍体毒剂诱导的环形微核率显著高于染色体断裂剂(分别为33.8±2.8,17.4±8.3;P=0.003),而圆形微核率显著低于后者(分别为51.6±6.5,72.3±9.1;P＜0.0001),肾形微核率有高于染色体断裂剂诱导的微核的趋势,但差别无显著性(分别为14.6±6.7,10.2±6.3,P=0.07);两类诱变剂诱导的3种类别的微核95%可信区间差异很大,其中圆形微核率和环形微核率完全分离;②得到通过微核形态区分两类诱变剂的判别方程.结论:微核的圆形、环形和肾形的发生率可用于区分非整倍体毒剂与染色体断裂剂的参考.     

Correlation of dietary aflatoxin B1 levels with excretion of aflatoxin M1 in human urine

Corn and peanut oil (total, 253 samples) were collected from 32 households in Fushui county of the Guangxi autonomous region of the People's Republic of China, where high liver cancer incidence has been reported, every day over a period of 1 week and analyzed for aflatoxin B1 (AFB). A total of 252 urine samples were collected simultaneously from the residents in the households which were shown to have consumed AFB and were analyzed for aflatoxin M1 (AFM) by a competitive direct enzyme-linked immunosorbent assay. A good correlation between total dietary AFB intake and total AFM excretion in human urine was observed during a 3-day study. A regression equation of 0.143 plus 0.0135 multiplied by the amount of AFB consumed was observed. Between 1.23 and 2.18% of dietary AFB was found to be present as AFM in human urine. A good correlation was also observed between the AFB concentration in corn and the AFM concentration in human urine. The results suggest that analysis of AFM in urine by enzyme-linked immunosorbent assay could be used as an index for human exposure of AFB in an extensive epidemiological study.     

Efficient activation of aflatoxin B1 by cytochrome P450 2A13, an enzyme predominantly expressed in human respiratory tract

The worldwide human exposure to aflatoxin B1 (AFB1), particularly in developing countries, remains to be a serious public health concern. Although AFB1 is best known as a hepatocarcinogen, epidemiological studies have shown a positive association between human lung cancer occurrence and inhalation exposure to AFB1. Cytochrome P450 (CYP)-catalyzed metabolic activation is required for AFB1 to exert its carcinogenicity. Previous studies have identified CYP1A2 and CYP3A4 as the major enzymes for AFB1 activation in human liver. However, the key CYP enzymes in human lung that can efficiently activate AFB1 in situ are unknown. In the present study, we demonstrate that CYP2A13, an enzyme predominantly expressed in human respiratory tract, has a significant activity in metabolizing AFB1 to its carcinogenic/toxic AFB1-8,9-epoxide and AFM1-8,9-epoxide at both low (15 microM) and high (150 microM) substrate concentrations. Under the same conditions, there was no detectable AFB1 epoxide formation by CYP2A6, which was also reported to be involved in the metabolic activation of AFB1. Consistent with the activity data, there was an approximately 800-fold difference in LC50 values of AFB1 (48-hr treatment) between Chinese hamster ovary (CHO) cells expressing CYP2A13 and CYP2A6 (50 nM versus 39 microM). We further demonstrate that amino acid residues Ala117 and His372 in CYP2A13 protein are important for AFB1 epoxidation and its related cytotoxicity. Our results suggest that CYP2A13-catalyzed metabolic activation in situ may play a critical role in human lung carcinogenesis related to inhalation exposure to AFB1.     

Detection of aflatoxins and related metabolites by radioimmunoassay

Rabbit (outbred albino New Zealand White) antisera have been raised against aflatoxin B1 (AFB1) using as immunogen conjugates in which the hapten was coupled to bovine serum albumin (BSA) either through C1 or C8 with the oxime and the dichloride derivatives of AFB1 as intermediates. Radioimmunoassay (RIA), with [3H]AFB1 as tracer, showed that the antiserum prepared with the conjugate in which BSA was coupled to the AFB1 oxime derivative was highly specific to AFB1, whereas the antiserum raised against the conjugate in which BSA was coupled to AFB1 through the AFB1Cl2 derivative (C-antiserum) cross-reacted to a large extent with other aflatoxins, including aflatoxin M1, an important urinary metabolite of AFB1 in several species including humans. AFB1-related metabolites in the urine of inbred BD IV adult male rats given AFB1 orally at doses from 600 pmol to 385 nmol can easily be followed over 9 days by RIA in which the "cross-reactive" C-antiserum is used. This suggests that similar methodologies could be used for the monitoring of human exposure to AFB1.     

Enhancement of GST-P-positive liver cell foci development by nivalenol, a trichothecene mycotoxin.

In order to elucidate whether T-2 toxin (T-2) and nivalenol (NIV), the naturally occurring trichothecene mycotoxins in food and feed, are carcinogenic or possess an ability to modulate aflatoxin B1 (AFB1)-induced hepatocarcinogenicity, a medium-term liver bioassay was carried out. F344 male rats were given a single i.p. injection of diethylnitrosamine (DEN, 200 mg/kg), and then fed the test trichothecenes in diet (2 and 5 p.p.m. T-2 or 6 p.p.m. NIV) for 6 weeks beginning 2 weeks after the injection. Some control groups received DEN alone. For synergism between AFB1 and the trichothecenes, DEN-initiated rats as above were given a single i.p. injection of AFB1 (0.5 mg/kg) 2 weeks later and were fed a NIV-containing diet (6 p.p.m.) for 6 weeks. The other control group received the vehicle alone. Control rats not initiated with DEN were also treated with AFB1, NIV or T-2 alone as above. All rats were subjected to a two-thirds partial hepatectomy (PH) at week 3 and killed at week 8, and liver sections were analyzed by glutathione S-transferase placental form (GST-P) expression. In rats that did not receive DEN, AFB1 alone enhanced both the numbers and areas of GST-P-positive foci as reported earlier, while NIV or T-2 alone induced no marked changes. In rats initiated with DEN, AFB1 caused a marked expression of GST-P, and thus the hepatocarcinogenicity of AFB1 was reconfirmed. The expression of GST-P foci in rats fed T-2 or NIV was found to be at background level, indicating that the hepatocarcinogenicity was not predicted for the trichothecene mycotoxins such as T-2 and NIV by this medium-term bioassay system. In the group initiated by DEN followed by AFB1, on the other hand, an elevation of both the numbers and areas of GST-P-positive foci was observed by the subsequent feeding of rats with NIV, and this elevation was statistically significant from the sum totals of individual data of AFB1 or NIV alone. From this evidence, it is predicted that NIV causes an enhancing effect on AFB1-induced hepatocarcinogenesis.     

Aflatoxin B1-DNA adducts and hepatitis B virus antigens in hepatocellular carcinoma and non-tumorous liver tissue.

Studies were carried out to test the hypothesis that exposure to aflatoxin B1 (AFB1) is common among individuals with hepatocellular carcinoma (HCC) who are also chronically infected with hepatitis B virus (HBV). Experiments were also carried out to determine whether there is a close association between the presence of AFB1-DNA adducts and the expression of one or more HBV antigens in the tumor or non-tumor regions of the liver. Twenty-seven paired tumor and non-tumor liver tissues of HCC patients from Taiwan were analyzed. Monoclonal antibody 6A10, generated against the imidazole ring-opened persistent form of the major N-7 guanine adduct of AFB1, was used for adduct detection by both indirect immunofluorescence and competitive enzyme-linked immunosorbent assay. An avidin-biotin complex staining method was used for the detection of HBsAg and HBxAg in liver sections. A total of 8 (30%) HCC samples and 7 (26%) adjacent non-tumor liver tissue samples from Taiwan were positive for AFB1-DNA adducts. For HBsAg, 10 (37%) HCC samples and 22 (81%) adjacent non-tumorous liver samples were positive while 9 (33%) HCC samples and 11 (41%) adjacent non-tumor liver samples were HBxAg-positive. No association with AFB1-DNA adducts was observed for HBsAg and HBxAg. These results suggest that both AFB1 exposure and carrier status of HBsAg/HBxAg may be involved in the induction of HCC in Taiwan.     

果蔬饮料胡萝卜汁拮抗致突变物作用初步研究

  目的 检测果蔬饮料胡萝卜汁抗突变作用的效应情况，为开发果蔬饮品提供实验数据。方法 利用鼠伤寒沙门菌营养缺陷型Ames点实验改良法，37 ℃恒温培养48 h。计算在纸圈内所产生的回复变菌落数，据测试物和溶剂对照的细菌回复变集落数的差异，判断是否有抑制突变的作用。结果 TA98，TA100菌株均在正常范围内。未观察到所有实验的样品有致突变作用现象。结论 新黑田胡萝卜汁和双岐因子型2 ％醋酸胡萝卜汁对MNNG诱导TA100，新黑田胡萝卜汁+ 2 ％醋和农家胡萝卜汁对AFB1诱导TA98+S9的抑制率较高，剂量效应关系明显，新黑田胡萝卜汁和新黑田胡萝卜汁+ 2 ％醋对AFB1、新黑田胡萝卜汁对BAP诱导A100+S9也有较高的抑制，但不构成剂量效应关系。     

Promotion of aflatoxin B1 carcinogenesis by the natural tumor modulator indole-3-carbinol: influence of dose, duration, and intermittent exposure on indole-3-carbinol promotional potency

Indole-3-carbinol (13C), a secondary metabolite from cruciferous vegetables, inhibits aflatoxin B1 (AFB1) hepatocarcinogenesis in trout (Bailey et al., J. Natl. Cancer Inst., 78: 931-934, 1987) and rats (Selivonchick et al., unpublished results) when given prior to and with carcinogen but promotes carcinogenesis in both species when given continuously following AFB1 initiation. Since human 13C intake may not be continuous, and the promotional stimulation may be reversible, we have assessed 13C promotion using delayed and discontinuous exposure protocols. Following initiation with AFB1, 13C was fed to trout for varying periods of time, with varying lengths of delay after initiation and continuous or intermittent patterns of 13C treatment. Promotional enhancement of tumor incidence by 13C was found to be significant when 13C treatment was delayed for several weeks or months after the initial AFB1 challenge. Promotion also was found to increase with length of exposure to 13C treatment and to be decreased but still evident when 13C was given in alternating months or weeks, or twice per week only. These results do not support the idea that promotional stimulation in hepatocarcinogenesis is a reversible phenomenon. To quantify 13C promotional potency in terms of its dietary concentration, a series of AFB1 tumor dose-response curves was established, each with a different level of 13C fed continuously following AFB1 initiation. The resultant tumor dose-response curves, plotted as logit percentage of incidence versus log AFB1 dose, were displaced parallel toward lower AFB1 50% tumor take (TD50) values with increasing 13C concentration. The level of 13C that halves the AFB1 dose for 50% tumor incidence was calculated to be approximately 1000 ppm 13C, fed continuously, with no substantial threshold for promotion. By comparison, 13, when fed before and with AFB1, shows a 50% inhibitory value (13C concentration that doubles the dose of AFB1 for 50% tumor incidence) in trout of 1400 ppm 13C [Dashwood et al., Carcinogenesis (Lond.), 10: 175-181, 1989]. Thus the potential for 13C as a dietary additive to promote prior hepatic initiation events when fed continuously is approximately as great as its potential to inhibit concurrent AFB1 initiation.