Ki-67、p53蛋白在胃癌组织中的表达及临床意义

目的 研究Ki-67、p53蛋白在胃癌组织中的表达情况及临床意义.方法 选择我院病理科胃癌组织标本60例,同时选择癌旁组织标本20例,应用免疫组化SP法检测 Ki-67、p53蛋白的表达情况.结果 Ki-67、p53蛋白在胃癌组织中的阳性表达率高于癌旁组织,差异有统计学意义(P<0.05);Ki-67、p53蛋白的阳性表达率在有淋巴结转移、低度分化、浸润肌层及浆膜层的组织中高于无淋巴结转移、高、中度分化、浸润黏膜层及黏膜下层的组织,差异有统计学意义(P<0.05,P<0.01);Ki-67与p53蛋白在胃癌组织中的表达呈正相关(r=0.679,P<0.01).结论 Ki-67、p53蛋白均参与胃癌的发生和发展,二者可作为判断胃癌恶性程度及评估预后的指标.     

结直肠癌患者组织细胞角蛋白7、尾型同源盒转录因子-2、抑制P53基因蛋白表达及意义

目的 分析结直肠癌患者组织细胞角蛋白7(CK7)、尾型同源盒转录因子-2(CDX2)、抑制P53基因蛋白（P53）表达及意义。方法 选取2016年8月至2021年8月于景德镇市第三人民医院确诊的60例结直肠癌（CRC）患者的癌组织及癌旁组织石蜡标本,采用免疫组化检测组织中的CK7、CDX2、P53阳性表达率。分析各指标阳性表达率与临床病理特征的关系。结果 CK7、CDX2在癌组织中的阳性表达率低于癌旁组织,差异有统计学意义（P<0.05）;P53在癌组织中的阳性表达率高于癌旁组织,差异有统计学意义（P<0.05）;有淋巴结转移癌组织中的CK7、CDX2阳性表达率低于无淋巴结转移癌组织,差异有统计学意义（P<0.05）;低分化、浆膜浸润型、Dukes C+D期癌组织中的CDX2阳性表达率低于高分化、非浆膜浸润型、Dukes A+B期癌组织,差异有统计学意义（P<0.05）;有淋巴结转移、低分化、浆膜浸润型、Dukes C+D期中P53阳性表达率高于无淋巴结转移、中高分化、非浆膜浸润型、Dukes A+B期癌组织,差异有统计学意义（P<0.05）。结论 在CR...     

ICAM-1、CD82的表达差异对结直肠癌肝转移影响的临床研究

目的对细胞间粘附分子-1(ICAM-1)、CD82的表达差异对结直肠癌肝转移的影响进行相关研究。方法行外科手术治疗结直肠癌患者68例,以自身癌旁正常黏膜组织为对照组,以自身癌组织黏膜组织为研究组,对比观察CD82和ICAM-1蛋白在癌组织的表达情况;对比分析两组CD82及ICAM-1蛋白的表达差异对结直肠癌肝转移的影响及两组的相互关系。结果 68例结直肠癌患者的癌组织中ICAM-1表达明显高于癌旁组织(P<0.05),但在正常大肠黏膜组织中无表达;CD82在结直肠癌组织中表达则明显低于癌旁组织(P<0.05)。同时,ICAM-1、CD82的表达与结直肠癌临床Dukes分期及转移复发有密切关系(P<0.05)。结论可将ICAM-1的表达作为肿瘤发生、浸润、转移的重要判断因子,ICAM-1和CD82联合检测对有效判定肿瘤的恶性程度以及转移情况等均具有临床指导作用。     

结直肠癌中Bcl-2、Bag-1蛋白的表达及其意义

目的探讨抗凋亡基因Bcl-2、Bag-1在正常结肠黏膜、结肠腺瘤和结直肠癌中的表达变化及与结直肠癌发生、发展和转移的关系.方法采用免疫组化S-P法,分别检测20例正常结肠黏膜、35例结肠腺瘤和82例结直肠癌组织中Bcl-2、Bag-1 蛋白表达情况.结果 Bcl-2蛋白在正常结肠黏膜、结肠腺瘤和结直肠癌组织中阳性表达率分别为25.0%,80.0%和65.0%.结肠腺瘤和结直肠癌组织中Bcl-2蛋白表达阳性率均显著高于正常结肠黏膜组织（P＜0.05）,而结肠腺瘤与结直肠癌相比,前者高于后者（P＜0.05）.Bcl-2蛋白表达水平与结直肠癌患者的年龄、性别、肿瘤分化程度、Duke＇s分期及淋巴结转移无关（P＞0.05）.Bag-1蛋白在正常结肠黏膜、结肠腺瘤和结直肠癌组织中阳性表达率分别为10.0%,60.0%和81.0%,阳性表达率呈上升趋势,差异有显著性（P＜0.05）,Bag-1蛋白表达水平与结直肠癌患者的年龄、性别无关（P＞0.05）,而与肿瘤分化程度、Duke＇s分期及淋巴结转移有关（P＜0.05）.其中结直肠癌组织中Bcl-2蛋白表达与Bag-1蛋白表达呈正相关（P＜0.05）.结论 Bcl-2、Bag-1蛋白高表达在结直肠癌的发病过程中均发挥十分重要作用,而Bag-1表达水平与结直肠癌的恶性程度有关,可作为预测结直肠癌浸润转移潜能的新的生物学指标.     

DLL4在结直肠癌中的表达及其与浸润转移的关系

目的检测结直肠癌组织中DLL4的表达,并探讨其与结直肠癌发生及浸润转移的关系。方法应用免疫组化EnVision法检测70例结直肠癌组织及其相应的40例癌旁非典型增生组织和20例正常结直肠黏膜组织中DLL4的表达。结果结直肠癌组织中DLL4的阳性表达率高于癌旁非典型增生组织和正常结直肠黏膜组织（P〈0.05）;淋巴结转移组结直肠癌组织中DLL4的阳性表达率高于无淋巴结转移组（P〈0.05）;浸润至浆膜外结直肠癌组织中DLL4的阳性表达率高于浸润至浅肌层及深肌层者（P〈0.05）。结论 DLL4过度表达可能参与结直肠癌的发生及浸润转移过程。     

MMR蛋白、p53、HER-2与Ki-67在子宫内膜癌组织中表达及与临床病理特征的关系

目的 探讨错配修复(MMR)蛋白、抑癌基因p53(p53)、表皮生长因子受体2(HER-2)与肿瘤增殖抗原(Ki-67)在子宫内膜癌组织中表达及与临床病理特征的关系。方法 选取濮阳市人民医院2019年1月至2021年1月收治的100例(均完成随访)子宫内膜癌患者为研究对象,采用免疫组化法检测子宫内膜癌组织和癌旁组织中MMR蛋白(MLH1、PMS2、MSH2、MSH6)、p53、HER-2、Ki-67表达情况,比较不同病理学参数子宫内膜癌组织中MMR、p53、HER-2、Ki-67的表达情况,分析子宫内膜癌组织中MMR、p53、HER-2、Ki-67表达与临床病理学参数的关系,分析MMR、p53、HER-2、Ki-67表达与子宫内膜癌患者预后关系。结果 子宫内膜癌组织中MMR表达缺失率、p53、HER-2、Ki-67阳性表达率高于癌旁组织(P<0.05);不同病理类型患者子宫内膜癌组织MMR表达缺失率、p53、HER-2、Ki-67阳性表达率比较：Ⅰ～Ⅱ期低于Ⅲ～Ⅳ期,高分化<中分化<低分化,无淋巴结转移低于有淋巴结转移(P<0.05);子宫内膜癌组织MMR表达缺...     

CPNE7在结直肠癌组织中的表达及临床意义

目的：研究结直肠癌患者肿瘤组织中CPNE7的表达及与患者病情、预后的关系。方法：回顾性选择90例结直肠患者为研究对象,经手术获取结直肠癌组织标本和癌旁正常黏膜组织标本,采用Western blotting免疫印迹法检测标本组织和肿瘤细胞系中CPNE7的表达,采用免疫组化检测结直肠癌组织芯片中CPNE7的表达,分析CPNE7表达水平与肿瘤病理特征的关系及在预后评估中的应用。结果：CPNE7在结直肠癌细胞株中的表达明显高于正常结直肠上皮细胞株,且与癌旁正常组织比较,CPNE7在结直肠癌组织中的表达明显升高。90例患者中共84例(93.33%)出现肿瘤组织中CPNE7表达量高于癌旁组织(P<0.05)。肿瘤组织中CPNE7高表达率为50.00%,高于癌旁组织的7.78%(P<0.05)。淋巴结转移N1、N2者CPNE7高表达率均高于N0者(P<0.05),TNM分期Ⅲ期者CPNE7高表达率高于Ⅰ期、Ⅱ期者(P<0.05)。Kaplan-Meier生存曲线分析发现,CPNE7表达水平与患者预后相关(P<0.05)。结论：结直肠癌患者肿瘤组织中CPNE7的表达较癌旁...     

NF-κB在结直肠癌中的表达及与凋亡的关系

目的探讨核因子-κB(nuclear factor-κB,NF-κB)在结直肠癌组织中的表达及与凋亡的关系。方法采用免疫组织化学SP法、TdT介导的dUTP缺口末端标记技术原位观察65例结直肠癌组织及其对照癌旁正常黏膜组织中NF-κB的表达情况和细胞凋亡情况。结果结直肠癌中NF-κB的阳性率为58.46%(38/65),显著高于对照组(P<0.05)。癌旁和癌组织凋亡指数(AI)分别为(8.23±1.57)%和(3.25±1.82)%,两者比较差异有统计学意义(P<0.05)。NF-κB的表达与癌组织的分化程度、淋巴结转移和Dukes分期相关(P<0.05)。结论 NF-κB在结直肠癌组织中高表达,NF-κB表达可抑制结直肠癌的细胞凋亡,并与病理分期、有无淋巴结转移等恶性临床病理特征有密切相关性,提示NF-κB在结直肠癌的发生、发展及预后中发挥重要作用。     

MK、VEGF在结直肠癌中的表达及其临床意义

目的研究结直肠癌中中期因子(midkine,MK)和VEGF的表达与临床病理学特征关系。方法应用免疫组织化学方法检测49例直肠癌组织以及20例结直肠癌癌旁组织中MK、VEGF表达。结果 MK、VEGF表达在结直肠癌组织中均显著高于癌旁正常组织(P<0.05);结直肠癌组织MK、VEGF表达与浸润深度、淋巴结转移、Dukes’分期呈正相关(P<0.05);MK与VEGF表达呈正相关性(P<0.05)。结论 MK、VEGF在直肠癌组织中的表达较癌旁组织成显著性高表达,协同促进了结直肠癌的发展,可作为结直肠癌预后判断的选择指标。     

中青年宫颈癌患者组织Ki-67、CK8/18、CK7表达及相关性分析

目的 研究中青年宫颈癌患者组织细胞增殖核抗原67(Ki-67)、细胞角蛋白8/18(CK8/18)、CK7表达及相关性。方法 选取2018年5月至2019年5月76例中青年宫颈癌患者，取术中宫颈癌组织和癌旁正常组织(癌旁2 cm)。采用免疫组织化学法检测两种组织中Ki-67、CK8/18、CK7阳性表达情况，分析宫颈癌组织中Ki-67阳性表达与CK8/18、CK7阳性表达的相关性。并比较不同病理特征患者Ki-67、CK8/18、CK7阳性表达情况，分析各指标与宫颈癌病理特征的相关性。术后随访3年，应用生存曲线分析宫颈癌组织中Ki-67、CK8/18、CK7阳性与阴性表达患者生存情况。结果 中青年宫颈癌患者宫颈癌组织中Ki-67、CK8/18、CK7阳性率均高于癌旁正常组织(P<0.05);宫颈癌组织中Ki-67与CK8/18、CK7阳性率呈正相关(r值分别为0.351,0.328,P<0.05);临床分期Ⅲ～Ⅳ期、有淋巴结转移、浸润深度T3～T4级宫颈癌患者癌组织中CK8/18、CK7阳性率分别高于临床分期Ⅰ～Ⅱ期、无淋巴结转移、浸润深度T1～T2级宫颈癌患者(P<0...     

支气管哮喘血清可溶性细胞间黏附分子-1和内皮细胞黏附分子-1的表达

目的　探讨可溶性细胞间黏附分子 - 1(s ICAM- 1)和血管内皮细胞黏附分子 - 1(s VCAM- 1)在支气管哮喘发病中的意义。方法　对支气管哮喘患者 2 3例和健康人 2 0名 (年龄均在 15～ 45岁之间 ) ,采用酶联免疫双抗体夹心法 (EL ISA)测定血清中的 s ICAM- 1和 s VCAM- 1;利用荧光酶联免疫法 (Uni- CAP系统 )分析血清中总 Ig E(t Ig E)和特异性 Ig E(s Ig E)。结果　血清 s ICAM- 1、s VCAM- 1、t Ig E水平测定哮喘组均高于对照组 (P<0 .0 1) ;血清中以户尘螨和蒿草花粉的特异性 Ig E含量增高为主 ;经多元逐步回归分析提示血清总 Ig E含量与s ICAM- 1存在线性关系 ,其复相关平方 (R- square)为 0 .5 0 2 ,标准偏回归系数为 0 .0 97,t=2 .841,P=0 .0 2 18。结论　支气管哮喘患者的 s ICAM- 1和 s VCAM- 1含量显著高于正常人 ;血清 s ICAM- 1与血清总 Ig E存在线性依存关系。     

1-Phenyl-1H-indazole derivatives with analgesic and anti-inflammatory activities.

The synthesis of 4-hydroxy-1-phenyl-1H-indazole-5-acetic acid 5 4-methoxy-1-phenyl-1H-indazole-5-yl-acetic acid 7 and 5-benzyl-1-phenyl-1H-indazol-4-ol 8, starting from 1,5,6,7-tetrahydro-1-phenyl-4H-indazol-4-one, is described. These compounds showed in mice an analgesic activity superior to that of acetylsalicylic acid and comparable to that of dipyrone; moreover, compound 5 exhibited an appreciable anti-inflammatory activity in rats. Grossbehavioral effects and acute toxicity in mice are also reported.     

Levels of sICAM-1, sVCAM-1 and MCP-1 in patients with hyperlipoproteinemia IIa and -IIb

OBJECTIVE: Hyperlipoproteinemia is one of the factors that are involved in the development of atherosclerosis. One of the mechanisms through which these high plasma lipid levels trigger the formation of atherosclerotic lesions is a change in the expression of adhesion molecules on endothelial and smooth muscle cells. The aim of this study was to evaluate the plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemoattractant protein-1 (MCP-1) in patients with Type IIa (HLP-IIa) and IIb (HLP-IIb) hyperlipoproteinemias. SUBJECTS: Twenty patients with HLP-IIa, 20 patients with HLP-IIb and 23 control subjects were studied. To accurately evaluate adhesion molecule levels, we excluded those hyperlipemic patients and control subjects who had an inflammatory disease. METHODS: Plasma sICAM-1, sVCAM-1 and MCP-1 levels were measured by the ELISA method. RESULTS: sVCAM-1 levels in HLP-IIa and HLP-IIb patients (535 +/- 27 ng/ml and 545 +/- 22 ng/ml, respectively) did not differ significantly from those in the control group (558 +/- 20 ng/ml). sICAM-1 levels were significantly higher in patients with HLP-IIa and HLP-IIb (279 +/- 10 ng/ml and 322 +/- 12 ng/ml, respectively) compared to the control group (226 +/- 10 ng/ml). MCP-1 levels were significantly higher in HLP-IIa and HLP-IIb patients (151 +/- 12 pg/ml vs 154 +/- 12 pg/ml, respectively) compared to healthy controls (98 +/- 4 pg/ml). sICAM-1 levels in the HLP-IIb group were significantly higher than in the HLP-IIa group. CONCLUSION: The results of the study suggest that lipid abnormalities affect the levels of adhesion molecules and chemokines in plasma.     

CYP1B1、NQO1基因多态性与肺癌易感性关系的研究

目的研究内蒙古地区蒙古族与汉族人群的CYP1B1和NQO1基因多态性及吸烟状况与肺癌易感性的关系。方法采用PCR-RFLP技术对CYP1B1基因L432V位点和NQO1基因C609T位点多态性进行检测。结果 (1)CYP1B1基因L432V位点基因型分布频率在蒙古族和汉族健康人群中差异无统计学意义(χ2=1.220,P> 0.05);NQO1基因C609T位点基因型分布频率在蒙古族和汉族健康人群中差异无统计学意义(χ2=0.221,P> 0.05)。(2)在蒙古族和汉族人群中,NQO1 C/T和T/T基因型有明显增加患肺癌风险性的作用(汉族人群OR:1.461,2.278,P <0.05;蒙古族人群OR:1.493,2.040,P <0.05),而CYP1B1 C/G和G/G基因型无明显增加患肺癌风险性的作用(汉族人群OR:1.271,1.614,P> 0.05;蒙古族人群OR:0.970,1.758,P> 0.05)。(3)在汉族人群中,携带CYP1B1 C/G+G/G基因型的吸烟者患肺癌的危险性高于携带C/C的非吸烟者(OR:2.152,P <0.05);携带NQO1 C/C、C/T+T/T基因型的吸烟者患肺癌的危险性高于携带C/C的非吸烟者(OR:2.172,2.613,P <0.05)。在蒙古族人群中,携带CYP1B1 C/C、C/G+G/G基因型的吸烟者患肺癌的危险性高于携带C/C的非吸烟者(OR:1.409,1.765,P <0.05);携带NQO1 C/C、C/T+T/T基因型的吸烟者患肺癌的危险性高于携带C/C的非吸烟者(OR:2.479,2.729,P <0.05)。结论 (1)CYP1B1基因L432V位点基因型以及NQO1基因C609T位点基因型在内蒙古地区蒙古族和汉族健康人群中的分布不具有种族差异。(2)NQO1 C/T和T/T基因型显著增加内蒙古地区蒙古族和汉族患肺癌的易感性。(3)在蒙古族和汉族人群中,CYP1B1 C/G+G/G基因型以及NQO1 C/T+T/T基因型显著增加吸烟者患肺癌的易感性。     

Poisoning with 1-propanol and 2-propanol

1-Propanol and 2-propanol are isomers of an alcohol with three carbons. They are colorless liquids with a sweet odor. 1-Propanol is metabolized by alcohol dehydrogenase to propionic acid and presents with metabolic acidosis and elevated anion gap, whereas 2-propanol is metabolized by alcohol dehydrogenase to acetone and presents with rapidly developing (within 3-4 h after exposure) ketosis and ketonuria but without metabolic acidosis. We report a patient who simultaneously ingested a lethal dose of 1-propanol and 2-propanol as a hand disinfectant in hospital. The patient lost consciousness and stopped breathing within half an hour after ingestion. He was intubated and artificially ventilated. Initial laboratory results showed mixed acidosis with elevated anion gap, but ketonuria appeared only 12 h after admission and 6 h following the regaining of consciousness. Therefore, laboratory results in simultaneous poisoning with two isomers of alcohol are not just a sum of laboratory results obtained in isolated poisoning with each isomer because they influence each other's metabolism: 1-propanol retards the metabolism of 2-propanol to acetone. In conclusion, 1-propanol and 2-propanol poisoning presents early with mixed acidosis and elevated anion gap and only later with ketonuria.     

1-phenyl-1H-pyrazole derivatives with antiinflammatory, analgesic and antipiretic activities

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates 2 with phenylhydrazine gave the corresponding esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids 3 in high yields. Esters 3 were hydrolyzed to the relative carboxylic acids 4, which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles 5 in excellent yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with phenylhydrazine afforded methyl 1-phenyl-4-pivaloyl-1H-pyrazole-5-carboxylate 8 b, which was converted as above to the corresponding carboxylic acid 10 b and this to 1-phenyl-4-pivaloyl-1H-pyrazole 11 b. Starting from 5-methoxymethyl-1-phenyl-1H-pyrazole, 1-phenyl-1H-pyrazole-5-acetic acid 18 and its alpha-methyl derivative 19 were also synthesized. Compounds 18, 19, 10 b and 11 b showed a strong antiinflammatory activity in rats; the same compounds in general as well as 8 b, showed appreciable analgesic and antipyretic activities in mice and rats, respectively.     

Interaction of Sulfonylureas with Liver Uptake Transporters OATP1B1 and OATP1B3

Sulfonylureas (SUs) such as glibenclamide, gliclazide, glimepiride, glipizide and gliquidone are one of the first oral medicines available for the treatment of type 2 diabetes and are widely used for the treatment of hyperglycaemia. The hepatic transporters, organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), play an important role in the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. Drug–drug interactions mediated by OATP1B1/1B3 may result in the hepatic transporting change for drug substrates. The inhibitory effects of glibenclamide and glimepiride on sulfobromophthalein (BSP) uptake have been previously studied, and glibenclamide has been reported as the substrate of OATP1B3, but it remains unclear whether other SUs such as gliclazide, glipizide and gliquidone are substrates of OATP1B1 and OATP1B3. Here, we investigated the relationship between the five most commonly applied SUs (glibenclamide, gliclazide, glimepiride, glipizide, gliquidone) and OATP1B1 and OATP1B3. We performed uptake and inhibition assays in HEK293T cells stably expressing OATP1B1 or OATP1B3, respectively, and established a liquid chromatography–mass spectrometry (LC‐MS) method for the simultaneous measurement of five SUs. We demonstrated that gliclazide and glimepiride are substrates of OATP1B1 and glibenclamide and glipizide are substrates of OATP1B3. We also confirmed the interaction between these SUs and rosuvastatin. No transporting was observed for gliquidone, suggesting that it is not a substrate of either transporter.     

Cornell指数和Sokolow指数诊断左室肥大价值的研究

目的探讨Cornell指数和Sokolow指数诊断左室肥大(LVH)的价值。方法随机选择2008年1月～2009年8月我院住院患者200例,依据超声心动图测定左室心肌重量指数(LVMI)分为左室肥大组(A组)104例和正常组(B组)96例,然后根据心电图测量R_(avL)+Sv_3和Rv_5+Sv_1的值,计算Cornell指数和Sokolow指数的诊断敏感度、特异度及准确度。结果 Cornell指数的诊断敏感度为61.54%,特异度为83.33%,准确度为72.00%;Sokolow指数的诊断敏感度为37.50%,特异度为89.58%,准确度为62.50%,经过统计分析,Cornell指数和Sokolow指数敏感度(P<0.01),准确度(P<0.05),均有统计学意义,而特异度(P>0.05),无统计学差异。结论 Cornell指数标准是诊断左室肥大较好的指标。     

Interaction of deoxyschizandrin and schizandrin B with liver uptake transporters OATP1B1 and OATP1B3

1. Deoxyschizandrin and schizandrin B have diverse pharmacological effects, including hepatoprotective activity. We aim to study their hepatic uptake and their effects on the hepatic uptake of other clinical drugs mediated by OATP1B1 and OATP1B3.

2. Deoxyschizandrin exhibited a high affinity for OATP1B1 with K_m of 17.61?±?0.43?μM but a low affinity for OATP1B3. Similarly, schizandrin B also showed a strong affinity for OATP1B1 with K_m of 18.45?±?1.23?μM but a weak affinity for OATP1B3.

3. Atorvastatin and rifampicin could inhibit the uptake of deoxyschizandrin and schizandrin B mediated by OATP1B1.

4. Intriguingly, both deoxyschizandrin and schizandrin B significantly promoted the uptake of atorvastatin (with EC₅₀ of 50.58?±?8.08 and 24.70?±?5.82 µM, respectively) and rosuvastatin (with EC₅₀ of 13.46?±?2.70 and 8.99?±?4.73 µM, respectively) mediated by OATP1B1. Deoxyschizandrin could markedly promote the uptake of fluvastatin but inhibit the uptake of sodium taurocholate (TCNa) mediated by OATP1B1.

5. The promotion on hepatic uptake of statins mediated by OATP1B1 might lead to enhanced efficacy of cholesterol lowering and reduced risk of myopathy for hyperlipidemia patients when given statins together with deoxyschizandrin or schizandrin B.