磁共振波谱分析在早期帕金森病诊断及普拉克索疗效监测的应用

目的探讨磁共振波谱(MRS)在早期帕金森病(PD)患者应用及普拉克索疗效的价值。方法选取2016～2018年在北华大学附属医院神经科就诊符合PD诊断标准的早期PD患者40例,随机分为普拉克索用药组及未用药组,检测入院时、入院后6个月、1年PD患者3.0T MRS中脑黑质、纹状体中的乙酰天冬氨酸/肌酸(NAA/Cr)、胆碱/乳酸(Cho/Cr)值,对照组为20例年龄、性别匹配的健康者。结果用药组、未用药组入院6个月、1年时MRS中脑黑质、纹状体NAA/Cr、 Cho/Cr值较对照组明显降低(P0.05)。结论 MRS有助于早期PD患者的诊断及普拉克索疗效监测。     

脑卒中后抑郁患者抗抑郁治疗磁共振波谱分析研究

目的利用MRS技术研究影像学与脑卒中后抑郁(PSD)的关系。方法PSD组30例,符合DSMIV抑郁症状学、严重程度和病程标准。正常老年对照组20例。给予颅MRI、MRS检查。PSD组给予帕罗西汀(20～40)mg·qd。半年后随访颅MRI、MRS。结果PSD组患者双侧颞叶、丘脑NAA/Cr比值、Cho/Cr比值与正常对照组相比,存在统计学差异(P<005、P<001)。PSD组双侧Cho/Cr比值呈不对称性,左侧大于右侧(P<001)。PSD组汉密顿抑郁量表(HAMD)评分与左右颞叶Cho/Cr比值存在相关性(r左=0454,P=0012;r右=0373,P=0042)。PSD组患者在给予抗抑郁药物治疗后其双侧颞叶、丘脑NAA/Cr比值、Cho/Cr比值均有不同程度的下降(P<005);相关分析发现HAMD各因子分及总评分下降的程度与双侧颞叶、丘脑NAA/Cr、Cho/Cr比值下降程度之间不存在相关性。结论对脑卒中患者同时行MRI、MRS检查,测定双侧颞叶、丘脑Cho/Cr比值可以帮助早期判别PSD。     

帕金森病和帕金森综合征患者中脑黑质质子磁共振波谱的研究

目的 应用质子磁共振波谱(1H-MRS),观察帕金森病(PD)和帕金森综合征( PDS)患者中脑黑质内生物化学代谢物的变化,探讨1H-MRS在PD和 PDS诊断中的临床应用价值.方法 对30例PD、PDS患者和30例正常对照者双侧中脑黑质区进行1H-MRS检测,对比分析N-乙酰天门冬氨酸(NAA)/[胆碱(Cho)+肌酸(Cr)]、Cho/Cr、Cho/NAA比值的变化.结果 PD、PDS组与正常对照组中脑两侧黑质区NAA/(Cho+Cr)、Cho/Cr、Cho/NAA比值比较无显著性差异(P＞0.05). 结论 1H-MRS尚不能为PD和PDS提供临床诊断依据.     

MR化学位移成像脑代谢物改变与肝硬化的临床相关性

目的利用MRS评价肝硬化患者脑代谢物的异常变化及其与Child-Pugh分级、肝功指标的相关性。方法应用3.0T磁共振对52例乙型肝炎肝硬化患者(Child-Pugh A级患者20例、Child-Pugh B级患者14例、Child-Pugh C级患者18例)及15名慢性乙型肝炎患者(对照组)进行磁共振波谱分析,计算脑代谢物峰下面积Cho(胆碱)、Mi(肌醇)、NAA(N-乙酰天门冬氨酸)、Cr(肌酐)、Glx6(谷氨酰胺复合物)、脑代谢物峰下面积与Cr比值(NAA/Cr、Cho/Cr、Mi/Cr、Glx6/Cr)。结果①Child-Pugh A级组与对照组Mi、Glx6比较,差异有统计学意义。Child-Pugh B级组与Child-Pugh A级组Cho、Mi、Glx6比较,差异有统计学意义(P<0.01);Child-Pugh C级组与Child-Pugh B级组Cho、Mi比较,差异有统计学意义(P<0.01或P<0.05)。②Child-Pugh A级组与对照组Mi/Cr、Glx6/Cr比较,差异有统计学意义(P<0.01);Child-Pugh B组级与Child-Pugh A级组Cho/Cr、Mi/Cr、Glx6/Cr比较,差异有统计学意义(P<0.01或P<0.05);Child-Pugh C级组与Child-Pugh B级组Cho/Cr、Mi/Cr比较,差异有统计学意义(P<0.05)。③肝性脑病(HE)组与非肝性脑病组脑代谢物峰下面积比值Cho/Cr、Mi/Cr、Glx6/Cr比较,差异有统计学意义(P<0.01)。④Child-Pugh分级与Glx6/Cr呈正相关,与Cho/Cr、Mi/Cr呈负相关。⑤肝硬化患者TBil、PT与Cho/Cr、Mi/Cr呈负相关,与Glx6/Cr呈正相关。ALB与Cho/Cr、Mi/Cr呈正相关,与Glx6/Cr呈负相关。ALT与NAA/Cr、Cho/Cr、Mi/Cr、Glx6/Cr无明显相关性。结论肝硬化及肝性脑病患者存在脑代谢物浓度异常改变,可作为早期诊断肝硬化、肝性脑病及评价肝硬化、肝性脑病严重程度的一项指标。     

脑卒中后痴呆患者血胰岛素样生长因子-1与磁共振波谱的相关性研究

目的 了解胰岛素样生长因子-1(IGF-1)与脑卒中后血管性痴呆(VD)发生的关系及与磁共振波谱(MRS)的相关性.方法 脑卒中后VD组男性29例,女性8例,年龄63～81(平均72.4±6.8)岁.脑卒中后非VD组男性31例,女性11例,年龄64～80(平均71.1±7.3)岁.选择非脑卒中患者作为对照组男性30例,女性10例,年龄62～79(平均71.8±6.1)岁.脑卒中者在起病时予测定血IGF-1水平及头颅磁共振(MR)检查,对照组在入组时测定血IGF-1水平及头颅MR检查.MRS感兴趣区取中脑水平处的双侧颞叶海马区,分别计算左、右两侧各感兴趣区平均NAA/Cr、Cho/Cr 比值.结果 3组IGF-1间差异显著(F=8.63,P=0.004).脑卒中后VD组[(110.6.0±27.5)ng/ml]较脑卒中后非VD组[(154.1±59.3) ng/ml]和对照组[(161.3±60.5) ng/ml]明显减低且差异显著(t=6.74,6.98,均P＜0.001),脑卒中后非VD组与对照组间则无差异(t=0.37,P=0.72).NAA/Cr比值在脑卒中VD组最低,对照组最高;Choline/Creatine (Cho/Cr)比值在脑卒中VD组最高,对照组最低.脑卒中VD组颞叶海马区NAA/Cr、Cho/Cr比值与血IGF-1水平存在一定的相关性(γ=0.14,P=0.038;γ=-0.16,P=0.022).此外,脑卒中VD组MMSE评分与颞叶海马区NAA/Cr呈正相关,与Cho/Cr呈负相关(P＜0.05).结论 对于低血IGF-1水平、颞叶海马区NAA/Cr比值降低、Cho/Cr比值增高的脑卒中患者,应在认知功能方面给予密切观察和随访,及早进行认知功能方面的训练.     

磁共振波谱成像在轻微型肝性脑病诊断中的意义

目的:评价3T磁共振波谱成像(magnetic resonance spectroscopy,MRS)在轻微型肝性脑病(minimal hepatic encephalopathy,MHE诊断中的意义.方法:对30例肝硬化M H E患者、30例非M H E肝硬化患者和性别年龄相匹配3 0例正常对照组左侧顶叶采用单体素氢质子波谱点分辨自旋回波波谱序列(point-resolved echo spin spectroscopy,PRESS)进行MRS扫描,分别计算胆碱(choline,Cho)、肌醇(myo inositol,m Ins)、谷氨酰胺复合物(glutamine Glx)、肌酸(creatine,Cr)及N-乙酰天门冬氨酸(N-acetylaspartate,NAA)的峰下面积,并计算出与Cr比值:Cho/Cr、m Ins/Cr、Glx Cr、NAA/Cr进行3组间参数比较,并分析肝硬化患者顶叶MRS各参数与血氨值是否有相关性.结果:(1)3组间顶叶1H-MRS参数比较,与正常对照组相比,MHE组Cho/Cr及m Ins/Cr降低(P0.05),Glx/Cr增高(P0.01),NAA/Cr无变化;MHE组与非MHE肝硬化组比较,MHE组m Ins/Cr降低(P0.05);(2)肝硬化患者顶叶MRS各参数与血氨值无相关性.结论:MRS对于MHE的诊断具有一定的意义,并与静脉血氨值无相关性.     

3D-H~1磁共振波谱及表观扩散系数在老年前列腺良恶性病变中的价值

目的探讨3D-H1磁共振波谱(MRS)及表观扩散系数(ADC)值在老年前列腺良恶性病变中的价值。方法选择老年前列腺癌、前列腺增生、前列腺炎及健康志愿者各43例,均接受MRS及扩散加权成像(DWI)检查。比较各组病变组织3D-H1MRS特征、(Cho+Cr)/Cit及ADC值的差异。结果前列腺癌病变区(Cho+Cr)/Cit均值(2.861±0.872)显著高于其他各组(P<0.05)。前列腺癌病变区ADC均值(0.892±0.091)显著低于其他各组(P<0.05)。前列腺癌病变区胆碱(Cho)峰值+肌酸(Cr)峰值/枸橼酸盐(Cit)峰值与Gleason评分呈正相关(r=0.241,P=0.032),ADC值与Gleason评分呈负相关(r=-0.226,P=0.041)。结论 3D-H1MRS及ADC值可以为老年前列腺良恶性病变的鉴别诊断提供有价值的信息。     

MRS对恶性胶质瘤术后术区周围组织中Cho、NAA、Cr的观察及意义

目的用高场多体素磁共振波谱分析技术(MRS)观察恶性胶质瘤术后术区周围组织的病理生理代谢改变,并探讨临床意义。方法对32例恶性胶质瘤术后患者分别在术后2～9 d4、～10周1、3～6个月行MR常规扫描,范围为手术旁区约25 mm区域,参照区选择对侧大脑半球。采用MRS采集该区组织代谢物[胆碱(Cho)、N-乙酰天门冬氨酸(NAA)、肌酸(Cr)]信息,通过Func Tool软件包进行整合、分析,获得Cho/NAA、Cho/Cr、NAA/Cr值,输入SPSS12.0版软件进行统计分析。结果在术后不同扫描时段内术区强化旁区组织中Cho/NAA、Cho/Cr值均不同(P均<0.05)。术后4～10周变化最为显著,以Cho/NAA最为敏感。结论 MRS可有效明确恶性胶质瘤术后早期复发病灶,并对残存病灶转归进行观测。     

1HMRS在脑肿瘤鉴别诊断及胶质瘤分级中的应用研究

应用Philips Marconi Eclipse 1.5T超导型磁共振机,对60例经病理证实的脑肿瘤患者行单体素波谱(SVS)采集NAA、Cho、Cr、Lac、Lip和Ala峰,计算NAA/Cho、NAA/Cr和Cho/Cr比值.结果 显示,与正常侧相比,脑肿瘤均有NAA下降,Cho升高(P<0.05).不同肿瘤间Cho/Cr无明显差异,NAA/Cr和NAA/Cho具有统计学差异(P<0.05).各级别胶质瘤间NAA/Cr无明显差异,Cho/Cr和NAA/Cho具有高度统计学差异(P<0.01).Lip仅出现于高级别胶质瘤及转移瘤中.认为氢质子磁共振波谱(1HMRS)可以为脑肿瘤诊断与鉴别诊断、胶质瘤的组织学分级提供可靠信息.     

难治性癫痫患者的MRS海马代谢异常的观察研究

目的探讨磁共振波谱(MRS)在难治性癫痫诊治中的临床应用价值。方法对42例难治性癫痫患者和20例健康志愿者进行动态脑电图(EEG)、MRI和MRS检查。采用MRS检测双侧海马N-乙酰天门冬氨酸(NAA)、肌酸复合物(Cr)和胆碱复合物(Cho)的水平。结果①42例难治性癫痫患者中,14例MRI发现海马硬化,35例MRS异常。②与对照组相比,癫痫病侧组的NAA/(Cr+Cho)、NAA/Cr和NAA/Cho均显著降低;癫痫对侧组NAA/(Cr+Cho)、NAA/Cho低于对照组。③与对照组比较,海马硬化组(HS组)、非海马硬化组(NHS组)的上述3个指标均明显降低,HS组的上述3个指标均低于NHS组。结论 MRS检查在难治性癫痫的早期诊断和病灶定位方面比MRI具有更高的敏感性,可提高难治性癫痫患者海马生化异常改变的检出率。     

Characterization of MTHFR,GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia

The role of methylenetetrahydrofolate reductase (MTHFR C677T), glutathione S-transferases (GSTM1 and GSTT1 null, GSTP1 Ile105Val), and cytochromes p450 (CYP1A1*2A) genotypes in the etiology of childhood leukemia was simultaneously investigated. 144 Turkish children with acute lymphoblastic leukemia (ALL) and 33 with acute nonlymphoblastic leukemia (ANLL) were studied and compared with 185 healthy pediatric controls. The frequency of MTHFR genotype was insignificantly higher in ALL (7.7%) and ANLL (6.3%) than in controls (4.4%). Equal distribution of the GSTM1 null genotype was detected between ALL patients and controls (55%), while its incidence was slightly higher in ANLL patients (61.3%). Although GSTT1 null genotype was insignificantly lower in ALL patients (20.9%) than controls (22.7%), it was significantly underrepresented in ANLL patients (6.5%) (P = 0.05, OR 0.24, 95% CI 0.05-1.03). The homozygous frequency of GSTP1 genotype did not differ significantly between groups of ALL (3.7%), ANLL patients (9.1%) and controls (4.9%). Homozygous CYP1A1*2A genotype was underrepresented in ALL patients (1%) as compared to control (4.8%) but the differences did not reach to statistical significance (OR 0.21; 95% CI 0.03-1.72). Homozygosity for this genotype was not detected in ANLL patients. No particular association was noted between different combinations of combined genotypes and risk of development of childhood ALL and ANLL. These results suggested that there are no significant associations between the studied genotypes and the risk of developing either form of acute leukemia except GSTT1 null and homozygosity for CYP1A1 genotypes that may play protective roles in the development of ANLL in Turkish children.     

PICCO指导重症急性胰腺炎早期液体复苏的效果评价

目的 探讨脉搏连续心排血量（PICCO）指导早期液体复苏对重症急性胰腺炎（SAP）的临床意义。方法 选择我院消化科自2013年1月～2015年1月收治并应用PICCO指导早期液体复苏的37例SAP患 者作为PICCO组，同期选择应用中心静脉压（CVP）指导液体复苏的39例SAP患者作为对照组，比较两组48h内液体出入量、血管活性药物使用时间，以及机械通气时间、ICU住院时间和28天病死率。并应用受试者工作特征性（ROC）曲线分析28天病死率的危险因素。结果 共有76例患者入选，其中男41例，年龄58.76±13.84岁。两组间年龄、性别比例、入院血糖、血乳酸、血肌酐、氧和指数、平均动脉压、APACHE II 评分均无显著差异（P>0.05）。PiCCO组患者的0～6h补液量明显多于对照组（P<0.05），而6～72h补液量较对照组明显减少（P＜0.05）。PICCO组患者的血液净化率、机械通气时间、ICU住院时间均显著减少（P<0.05），但是两组患者应用血管活性药物的比例、导管相关感染率和28天病死率均无显著差别（P>0.05）。ROC曲线发现年龄（AUC 0.71, 95% CI, 0.63～0.76，P=0.03）和APACHE II评分（AUC 0.78, 95% CI, 0.67～0.91，P=0.02）为预测28天病死率的重要因素。结论PiCCO可以精确指导SAP患者早期液体复苏，并减少机械通气时间和ICU住院时间。     

Analysis of HLA-DRB1, DQA1, DQB1 haplotypes in Sardinian centenarians

Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a role in the association to diseases. Hence, we have evaluated, by amplification refractory mutation system/polymerase chain reaction (ARMS-PCR) the HLADQA1 and HLA-DQB1 allele frequencies in 123 centenarians and 92 controls from Sardinia to assess whether the association to HLA-DRB1 *15 allele may be due to the other genes involved in the HLA-DR,DQ haplotypes. The frequencies of HLA-DQA1, DQB1 haplotypes were not significantly modified in centenarians. Nevertheless by evaluating the frequency of DRB1 *15 linked haplotypes, we observed a not significant increase in centenarians of HLA-DQA1 *01, DQB1 *05 and HLA-DQA1 *01,DQB1 *06 haplotypes. These data suggest that these haplotypes might have a role in determining life span expectancy and longevity.     

The polymorphisms of GSTM1, GSTT1, HYL1*2, and XRCC1, and aflatoxin B1-related hepatocellular carcinoma in Guangxi population, China.

AIM: High incidence rates of hepatocellular carcinoma (HCC) in Guangxi, China, are primarily due to heavy aflatoxin B1 (AFB1) exposure via corn and groundnut consumption. This study was designed to examine the polymorphisms associated of three carcinogen-metabolizing genes (namely: GSTM1, GSTT1, and HYL1*2) and one DNA-repair gene (namely: XRCC1), and investigate their role as susceptibility markers for HCC. METHODS: We conducted a case-control study including 257 cases of cancer and 649 hospital-based age, sex, ethnicity, and hepatitis B virus infection-matched controls to examine the role of genetic polymorphisms of four genes (GSTM1, GSTT1, HYL1*2, and XRCC1) in the context of HCC risk for the Guangxi population. Genomic DNA isolated from 2ml whole blood was used to genotype GSTM1, GSTT1, HYL1*2, and XRCC1 by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. RESULTS: GSTT1-null genotype was not significantly associated with the risk of HCC, but GSTM1-null genotype [adjusted odds ratio (OR)=2.29, 95% confidence interval (CI)=1.59-3.31], HYL1*2 genotypes with 113 His allele (namely: YH/HH, adjusted OR=2.55, CI=1.78-3.65), and XRCC1 genotypes with 399 Gln allele (namely: AG/GG, adjusted OR=2.47, CI=1.72-3.54) increased the HCC risk. Compared with those individuals who did not express any putative risk genotypes as reference (OR=1), individuals featuring all of the putative risk genotypes [GSTM1-null, HYL1*2-YH/HH, and XRCC1-AG/GG] did experience a significantly greater cancer risk (adjusted OR=10.83, CI=5.44-21.59, P(interaction)<0.01). Additionally, the risk of HCC did appear to differ more significantly among individuals featuring risk genotypes and high-level or long-term AFB1 exposure, whose adjusted ORs (CIs) were 52.44 (17.51-157.08) and 326.93 (38.58-2770.52), respectively. CONCLUSIONS: The results suggest that carcinogen metabolism and DNA-repair pathways may simultaneously modulate the risk of HCC for Guangxi population, and, particularly for these having high-level or long-term AFB1 exposure.     

Association analyses of genetic polymorphisms of GSTM1, GSTT1, NQO1, NAT2, LPL, PRSS1, PSTI, and CFTR with chronic alcoholic pancreatitis in Japan

Background: Excessive consumption of alcohol is involved in the onset of pancreatitis. However, most of heavy drinkers do not always develop chronic pancreatitis. Various genetic factors appear to be involved in these individual differences in onset of chronic alcoholic pancreatitis. Here we investigated a possible association of alcoholic pancreatitis with polymorphisms of the various genes belong to the phase II detoxification enzymes responsible for metabolism of the oxidative compounds, and the several genes that have relevance to inherited pancreatitis. Methods: The subjects consisted of 53 patients with chronic alcoholic pancreatitis, 54 alcoholic patients without pancreatic dysfunction, and 42 healthy individuals. DNA was extracted from the peripheral nucleated blood cells of all subjects and genetic mutations and subtypes were analyzed by the PCR and RFLP methods. We examined the correlation between chronic alcoholic pancreatitis and variants of the phase II detoxification enzymes such as Glutathione S-transferase M1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), NADPH-quinone oxidoreductase 1 (NQO1), and N-acetyl transferase (NAT2). In addition, genes of lipoprotein lipase (LPL), cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (PSTI), and cystic fibrosis transmembrane conductance regulator (CFTR) were also analyzed. Results: Frequencies of the gene deletion of GSTM1 and GSTT1 in addition to the C-allele frequency of NQO1 tended to be higher in the alcoholic patients with (AlCP) or without pancreatic dysfunction (Alc) than in the healthy controls although the difference was not significant. The NAT2 gene showed no relation with Alc and AlCP patients. PSTI, LPL, PRSS1, and CFTR genes presented no association with chronic alcoholic pancreatitis. Conclusions: All genes analyzed in the present study lacked association with chronic alcoholic pancreatitis. However, the gene deletion of GSTM1 and GSTT1, and the C-allele of NQO1 cannot be ruled out for association with alcoholism.     

Serum levels of collagenase,stromelysin-1, and timp-1

Objective. To measure serum levels of collagenase (MMP-1), stromelysin-1 (MMP-3), and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in normal subjects and in patients with osteoarthritis (OA), and to assess how these correlate with biochemical and clinical indicators of disease activity in OA. Methods. Specific immunoassays were used to measure MMPs, TIMP-1, and antigenic keratan sulfate (KS). The total area of cartilage affected by the disease was measured (expressed as an articular index). Results. In the normal population (n = 118), the serum concentration of MMP-3, but not of MMP-1 or TIMP-1, increased with age and was approximately 2 times higher in males than in females. In the OA patients (n = 33), the serum levels of MMP-3, but not of MMP-1 or TIMP-1, were significantly elevated and correlated strongly with the articular index but poorly with objective and subjective functional capacity scores as well as with serum levels of antigenic KS and systemic parameters of inflammation. Conclusion. These findings illustrate the importance of matching patients and normal controls for age and sex in further studies of MMP-3 and are consistent with the hypothesis that MMP-3 might play an important role in the degradation of joint cartilage in OA. Further, serum levels of MMP-3 may prove useful for monitoring therapy for OA.     

CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer

Purpose As risk-modifiers of alcohol and tobacco effects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN). Methods A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion (AP) due to interaction and its 95% confidence interval (CI). Results SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93–6.35) and OR = 6.47 (95%CI: 2.92–14.35) for 19–30 g/day and >30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88–6.41) and OR = 7.65 (95%CI: 4.20–13.90) for 1–25 and >25 pack-years of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53–3.92). No differences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction emerged from gene–gene and gene–environment interaction analyses. An attributable proportion (AP) due to biological interaction of 0.65 (95%CI: 0.40–0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI: 0.10–0.72) resulted forever smokers with low fruit and vegetables consumption. Conclusions Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype.     

胰腺癌组织Shh、Gli1、Sufu、TAK1、p-TAK1蛋白的表达及其临床意义

目的 探讨Hedgehog信号通路重要成员Shh、Gli1、Sufu以及TAK1和磷酸化TAK1(p-TAK1)在胰腺癌组织中的表达及其与临床病理参数的相关性.方法 应用免疫组化法检测38例手术切除的胰腺癌组织及其配对的癌旁胰腺组织中Shh、Gli、Sufu、TAK1、p-TAK1蛋白的表达,分析它们与临床病理参数间的关系及它们相互间的关系.结果 胰腺癌组织Shh、Gli1、Sufu、TAK1、p-TAK1蛋白的表达率分别为86.8％(33/38)、52.6％(20/38)、68.4％(26/38)、55.3％(21/38)、52.6％(20/38),而癌旁胰腺组织中的表达均为阴性.Gli1表达与肿瘤远处转移及临床分期呈正相关(r值分别为0.524、0.361,P值均＜0.05);Sufu表达与患者性别相关(r=-0.378,P＜0.05);TAK1表达与胰腺癌临床分期呈正相关(r=0.468,P＜0.05);p-TAK1表达与临床分期、肿瘤远处转移呈正相关(r值分别为0.418、0.361,P值均＜0.05).胰腺癌组织中Gli1的表达水平与TAK1及p-TAK1呈正相关(P＜0.05).结论 Hedgehog信号通路及TAK1途径在胰腺癌的发生、发展中具有一定作用,且两条途径可能存在一定的相互作用.     

Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1"null" variants and the risk of acute leuke-mia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.