纤溶酶原激活物抑制物1与肝细胞癌

目的研究纤溶酶原激活物抑制物１（ＰＡＩ１）在肝细胞癌（ＨＣＣ）蛋白和ｍＲＮＡ水平的表达及其与ＨＣＣ生物学特性的关系。方法取ＨＣＣ石蜡标本４８例,肝良性肿瘤石蜡标本１２例（对照组）做免疫组化染色;液氮冻存ＨＣＣ标本２０例,肝血管瘤５例（对照组）做免疫印迹杂交。结果肝癌细胞与癌周细胞及对照组肝细胞相比,ＰＡＩ１抗原蛋白和ｍＲＮＡ表达显著升高,差异有显著意义,Ｐ值分别＜００１和＜０．０５。术后２年内死亡病例与生存病例相比,ＰＡＩ１阳性率有显著意义的升高,Ｐ＜００５。ＰＡＩ１和纤溶酶原激活物（ｕＰＡ）及其受体（ｕＰＡＲ）同时阳性患者与同时阴性患者相比,前者侵袭性病例较后者升高有显著性意义（Ｐ＜００５）。结论ＨＣＣ中ＰＡＩ１蛋白和ｍＲＮＡ表达明显增高。ＰＡＩ１与ＨＣＣ浸润转移和预后密切相关。     

血栓调节蛋白与肝细胞癌门静脉癌栓的关系

目的　了解血栓调节蛋白（ｔｈｒｏｍｂｏｍｏｄｕｌｉｎ,ＴＭ） 在肝细胞癌（ＨＣＣ） 病人血浆中的水平,探讨ＴＭ 与ＨＣＣ门静脉癌栓形成及侵袭和转移的关系。方法　采用酶联免疫吸附（ＥＬＩＳＡ） 夹心法,检测４５ 例ＨＣＣ病人和６ 例肝良性占位病人的术前和术后血浆ＴＭ 水平。结果　术前ＨＣＣ组血浆ＴＭ水平（１０±６）ｎｇ／ｍｌ 明显高于肝良性占位组（６．１ ±２．２）ｎｇ／ｍｌ,Ｐ＜ ０．０５;单发肝癌结节组（１２ ±６）ｎｇ／ｍｌ和无门静脉癌栓组（１１±６）ｎｇ／ｍｌ 明显高于多发肝癌结节组（８ ±５）ｎｇ／ｍｌ 和门静脉癌栓组（７ ±５）ｎｇ／ｍｌ,Ｐ＜ ０．０５;而ＴＭ 高低与肝癌大小、包膜是否完整、病理分化程度、ＡＦＰ值及肝癌伴肝硬化程度无关,各组比较Ｐ＞０．０５。肝良性占位组术前ＴＭ（６±２）ｎｇ／ｍｌ 与切除术后（５ ．９ ±１ ．８）ｎｇ／ｍｌ 相比差异无显著性,Ｐ＞０ ．０５ ;肝癌组术前（１０ ±５）ｎｇ／ｍｌ 与切除术后（８ ±４）ｎｇ／ｍｌ 相比差异有显著意义,Ｐ＜０ ．０５。结论　ＨＣＣ病人血浆中ＴＭ 水平可升高,ＴＭ 在抗ＨＣＣ门静脉癌栓形成过程中发挥重要作用。     

狼疮肾炎患者血与尿白细胞介素-8测定的临床意义

目的　探讨血清和尿中白细胞介素８（ Ｉ Ｌ８） 水平变化在系统性红斑狼疮（ Ｓ Ｌ Ｅ） 及狼疮肾炎（ Ｌ Ｎ） 中的临床意义。方法　采用 Ｅ Ｌ Ｉ Ｓ Ａ 法对４７ 例 Ｓ Ｌ Ｅ 患者（ 含３７ 例 Ｌ Ｎ） 、１３ 例原发性慢性肾小球肾炎和１４ 例正常对照进行血清和尿中 Ｉ Ｌ８ 水平检测,比较分析其与 Ｓ Ｌ Ｅ 活动指数（ Ｓ Ｌ Ｅ Ｄ Ａ Ｉ） 、肾脏损害的相关关系。结果　 Ｓ Ｌ Ｅ 患者血清 Ｉ Ｌ８ 水平活动期为５５３ ｐｇ／ｍｌ（ 中位数,下同） 静止期为２６３８ ｐｇ／ｍｌ,明显高于正常对照组２０５４ ｐｇ／ｍｌ（ Ｐ ＜ ０００１） ,并且活动期高于静止期（ Ｐ ＜ ００５） ,血清 Ｉ Ｌ８ 水平与 Ｓ Ｌ Ｅ Ｄ Ａ Ｉ正相关（ ｒ ＝ ０６００３ , Ｐ ＜ ００５） ; Ｓ Ｌ Ｅ 患者尿 Ｉ Ｌ８ 显著高于正常对照组２０６７ｐｇ／ｍｌ（ Ｐ＜ ００５） ,且 Ｌ Ｎ 组２５２９ ｐｇ／ｍｌ 明显高于 Ｓ Ｌ Ｅ 无肾炎组为２１１ ｐｇ／ｍｌ 及原发性慢性肾小球肾炎组１９４１ ｐｇ／ｍｌ（ Ｐ 值均＜ ００５） ;肾脏组织病理狼疮活动指数（ Ａ Ｉ） 高者其血清、尿 Ｉ Ｌ８ 水平显著高于 Ａ Ｉ低者（ Ｐ ＜ ００５） 。结论　血清 Ｉ Ｌ     

裸鼠肝癌转移模型组织中细胞间粘附分子1的表达

研究细胞间粘附分子１（ＩＣＡＭ－１）在肝癌转移过程中的作用和作为预测肝癌转移标志物的价值。方法以裸鼠人肝癌转移模型为材料,以ｄｏｔｉｍｍｕｎｏ－ｂｌｏｔ的方法测定不同生长时间肝癌组织中ＩＣＡＭ－１的表达。结果ＩＣＡＭ－１在肝癌组织中的表达与肿瘤的生长时间呈明显的正相关（ｒ＝０．８８,Ｐ＜０．０１）,与肿瘤大小呈正相关（ｒ＝０．０５,Ｐ＜０．０５）,在肝癌转移发生后ＩＣＡＭ－１表达突然升高,以后维持在较高水平,肿瘤转移组高于无转移组（Ｐ＜０．０１）,多脏器转移组高于单脏器转移组（Ｐ＜０．０５）。结论组织中ＩＣＡＭ－１的表达可以反映裸鼠人肝癌的生长转移状态,可以作为预测其转移的标志物。     

原发性肝细胞癌中WAF1/CIP1基因的表达及其临床病理意义

目的　探讨原发性肝细胞癌（ＨＣＣ）中ＷＡＦ１／ＣＩＰ１ 基因ｍＲＮＡ 的表达与临床病理学指标的关系和意义。方法　采用半定量ＲＴＰＣＲ方法,检测ＷＡＦ１／ＣＩＰ１ 基因在３０ 例ＨＣＣ及其癌旁肝组织中的表达。结果　肝癌组织ＷＡＦ１／ＣＩＰ１ｍＲＮＡ 表达相对值低于其相应癌旁肝组织［（１ ．１０±０ ．４３）Ｕ 对（１．３１±０．４１）Ｕ,Ｐ＜０ ．０５］ ,有卫星灶形成的肝癌低于无卫星灶形成的肝癌［（０．８６ ±０．２９）Ｕ 对（１ ．３２ ±０．４４）Ｕ,Ｐ＜ ０．０１］ ,但其在ＨＣＣ的其他病理学指标中差异无显著性（ Ｐ＞０ ．０５） 。结论　ＷＡＦ１／ＣＩＰ１ 基因的表达异常可能参与ＨＣＣ的发生、发展,并与肝癌细胞的浸润和转移分子机制有关。     

氨甲酰血红蛋白在评价血液透析充分性中的意义

目的　评价氨甲酰血红蛋白（ Ｃａｒ Ｈｂ） 在血液透析（ Ｈ Ｄ） 充分性中的意义。方法　用高效液相色谱法测定正常对照组３６ 例,非透析慢性肾功能衰竭５１ 例和 Ｈ Ｄ 患者３０ 例 Ｃａｒ Ｈｂ 含量（ 以每克血红蛋白含氨甲酰缬氨酸微克数,μｇ Ｃ Ｖ／ｇ Ｈｂ 表示） 。 Ｈ Ｄ 组 Ｃａｒ Ｈｂ 含量与尿素清除指数（ Ｋｔ／ Ｖ） 、尿素降低率（ Ｕ Ｒ Ｒ） 、平均时间尿素浓度（ Ｔ Ａ Ｃｕｒｅａ） 和校正蛋白质分解率（ｎ Ｐ Ｃ Ｒ） 作相关分析。结果　与对照组（３００ ±６１） 比较, Ｈ Ｄ 组 Ｃａｒ Ｈｂ 含量（１０２５ ±２８９） 显著升高（ Ｐ＜ ００１） ,但显著低于非透析组（１３９９ ±５２０）（ Ｐ＜ ００１） ; Ｋｔ／ Ｖ≤１１ 组 Ｃａｒ Ｈｂ 显著高于 Ｋｔ／ Ｖ＞ １１ 组［（１３５０ ±３１０）ｖｓ．（８８６±１２０） , Ｐ＜ ００１］ ; Ｃａｒ Ｈｂ 与 Ｋｔ／ Ｖ, Ｕ Ｒ Ｒ 呈负相关,但与 Ｔ Ａ Ｃｕｒｅａ 正相关。当 Ｋｔ／ Ｖ＞ １１ ,ｎ Ｐ Ｃ Ｒ＜ １０ ｇ· Ｋｇ１·ｄ１ 组 Ｃａｒ Ｈｂ 显著高于ｎ Ｐ Ｃ Ｒ≥１０ ｇ· Ｋｇ１·ｄ１ 组［（９６５ ±８３）ｖｓ．（８１５ ±１０４） , Ｐ     

慢性肾功能衰竭血浆P物质,心钠素与肾功能的关系

目的了解慢性肾功能衰竭（ＣＲＦ）患者血浆Ｐ物质（ＳＰ）、心钠素（ＡＮＰ）含量变化与肾功能的关系。方法采用放射免疫分析法检测正常对照组及ＣＲＦ组血液透析前后ＳＰ、ＡＮＰ，同时测定血清肌酐（Ｓｃｒ）。结果（１）透析前ＳＰ显著高于正常对照组（Ｐ＜００１），透析后ＳＰ高于透析前（Ｐ＜００５）；ＳＰ透析前与Ｓｃｒ呈正相关（ｒ＝０６６，Ｐ＜００５），ＳＰ透析后与Ｓｃｒ呈负相关（ｒ＝－０４６，Ｐ＜００５）；（２）透析前ＡＮＰ显著高于对照组（Ｐ＜００１），透析后ＡＮＰ显著低于透析前（Ｐ＜００５），ＡＮＰ透析前后与Ｓｃｒ呈正相关（ｒ＝０８２，Ｐ＜００５）；（３）透析前后ＳＰ变化值与ＡＮＰ变化值呈负相关（ｒ＝－０４８，Ｐ＜００５）。结论ＣＲＦ患者血浆ＳＰ、ＡＮＰ含量的变化与肾功能的改变有较明显的相关性。     

纤维素对化疗后大鼠肠结构和屏障功能的保护作用

目的评价纤维素对５氟尿嘧啶（５Ｆｕ）化疗后大鼠肠结构和屏障功能的影响。方法３０只Ｗｉｓｔａｒ大鼠随机分为饲料组（Ａ组）、肠内营养组（Ｂ组）和肠内营养加纤维素组（Ｃ组）,每组１０只。Ｂ组和Ｃ组为等氮和等热卡。它们分别进食或接受肠内营养支持８天。术后第４天用５Ｆｕ化疗,第３和第７天分别测肠通透性（Ｌ／Ｍ）,第８天测细菌移位、小肠和结肠的湿重、粘膜厚度、小肠的绒毛高度。实验前后分别测体重。结果Ｃ组体重丢失（－３１±３４ｇ）少于Ｂ组（－６６±５２ｇ）（Ｐ＜００５）,而Ａ组体重增加（４９±４３ｇ）,与Ｂ、Ｃ组比较差异有极显著意义（Ｐ＜００１）;Ｃ组的各项肠结构指标均优于Ｂ组（Ｐ＜００５）;化疗后Ｃ组和Ａ组的Ｌ／Ｍ变化无显著意义（Ｐ＞００５）,而Ｂ组的Ｌ／Ｍ有显著意义的升高（Ｐ＜００１）;Ｃ组与Ａ组的细菌移位率（２０％）低于Ｂ组（７０％）（Ｐ＜００５）。结论纤维素能保护５Ｆｕ化疗大鼠肠结构和屏障功能     

肿瘤浸润性淋巴细胞结合偶联半乳糖抗CD3单克隆抗体的肝脏靶向性研究

目的　探讨结合偶联半乳糖（ Ｇａｌａｃｔｏｓｅ , Ｇａｌ） 抗 Ｃ Ｄ３ 单克隆抗体（ Ａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ） 肿瘤浸润性淋巴细胞（ Ｔｕｍｏｒｉｎｆｉｌｔｒａｔｉｎｇ ｌｙｍｐｈｏｃｙｔｅｓ , Ｔ Ｉ Ｌ） 肝脏靶向性。 方法　本组把大鼠抗小鼠 Ｃ Ｄ 单克隆抗体和半乳糖偶联在一起,与３ Ｈ Ｔｄ Ｒ 标记 Ｔ Ｉ Ｌ结合后,从鼠尾静脉注入小鼠体内,在注射不同时间眼眶取血０５ ｍｌ,然后处死,切除肝、脾、肺,分别称重后进行放射性强度测定。 结果　结果显示：注射 Ｇａｌａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ Ｔ Ｉ Ｌ小鼠肝脏比注射单纯 Ｔ Ｉ Ｌ 的小鼠肝脏具有较高的放射性（ Ｐ＜ ００１） ,且该放射性持续较长一段时间,而脾、肺、血液内放射性强度差异无显著意义（ Ｐ＞ ００５ , Ｐ＞ ００５ , Ｐ＞ ００５） 。结论　该结果提示： Ｇａｌａｎｔｉ Ｃ Ｄ３ Ｍｃ Ａｂ Ｔ Ｉ Ｌ较单纯 Ｔ Ｉ Ｌ具有更好的肝脏靶向性。     

细胞稳定钙离子内流抑制剂羧基胺基咪唑抑制人肝癌诱导的血管形成

目的　观察细胞稳定钙离子内流抑制剂羧基胺基咪唑（ＣＡＩ） 抑制内皮细胞构建新生血管和人肝癌诱导血管形成的作用。方法　应用ＭＴＴ、Ｂｏｙｄｅｎ 培养皿和人工基质，研究ＣＡＩ对人脐静脉内皮细胞（ＨＵＶＥＣ）增殖、迁移、降解基质和构建血管能力的影响，利用ＬＣＩＤ２０ 瘤株裸鼠角膜模型观察ＣＡＩ对人肝癌诱导血管形成能力的影响。结果　ＣＡＩ的浓度超过１０ ｍｍｏｌ／Ｌ 时，内皮细胞的增殖明显抑制；与对照组相比，ＣＡＩ组细胞的迁移、降解基质和构建血管的能力下降（ Ｐ＜ ０．０５）；２ μｌ ＣＡＩ（１００μｍｏｌ／Ｌ）软膏动物涂眼，每日２ 次，ＣＡＩ组动物角膜新生血管的数目和长度分别小于和短于对照组（ Ｐ＜０．０５）。结论　ＣＡＩ能够明显抑制内皮细胞构建新生血管和人肝癌诱导的血管形成。     

AFP-IgM复合物在肝癌中的表达与临床关系

目的 分析甲胎蛋白-IgM免疫复合物(AFP-IgM)在肝细胞癌(HCC)中的含量,探讨AFP-IgM对诊断肝癌的临床意义.方法 采用酶联免疫吸附法与电化学发光法,对103名正常人、74例肝癌、43例肝硬化和58例脂肪肝病人血清AFP-IgM与甲胎蛋白(AFP)含量检测,并分析其与临床病理特点之间的关系.结果 应用ROC曲线确定AFP-IgM和AFP的最佳切割值分别为300 Au/ml和10μg/L作为诊断学意义的临界值.在此切割值下,肝癌组AFP-IgM和AFP血清水平均高于脂肪肝组和健康体检组(P<0.05).对早期(Ⅰ与Ⅱ期)肝癌诊断时,AFP-IgM的ROC曲线下面积大于AFP(0.91 vs 0.82);当肿瘤直径≤3 cm时,AFP-IgM为(1090.4±571.8)Au/ml,而当直径>3 cm时,AFP-IgM为(604.9±749.9)Au/ml,两者比较P<0.05.且AFP-IgM在诊断小肝癌时ROC曲线下面积大于AFP(0.92 vs 0.78);AFP-IgM对性别、年龄、乙型肝炎表面抗原、肿瘤数量、包膜的相关性无统计学意义(P>0.05),而与肿块大小和分期密切相关.结论 AFP-IgM对早期(Ⅰ与Ⅱ期)肝癌和小肝癌(≤3 cm)诊断具有重要作用,且对判断肝癌的肿瘤大小与分期等具有一定的临床意义.     

Regression of sclerosis in aging by an angiotensin inhibition-induced decrease in PAI-1

BACKGROUND: Glomerular and vascular sclerosis increase with aging, and angiotensin inhibitors ameliorate progression of this injury. We investigated the potential for achieving regression of existing age-related sclerosis, and the mechanisms by which angiotensin type 1 receptor antagonist (AIIRA) may affect remodeling of this sclerosis. We focused on plasminogen activator inhibitor-1 (PAI-1) because it is directly induced by angiotensin, inhibits matrix degradation, and may thus be pivotal in remodeling. METHODS: Eighteen-month-old male Sprague-Dawley rats were treated with the AIIRA losartan (N = 8, 80 mg/L, dry weight), sacrificed at age 21 and 24 months, and compared with age-matched untreated controls (N = 15). Blood pressure and renal function were monitored, and morphological, biochemical, and molecular analyses were done on aorta and kidney. RESULTS: Body weight increased in both groups. Mean arterial pressure (MAP) and serum creatinine remained normal (24-month MAP 115 +/- 8 vs. 113 +/- 6 mm Hg, controls vs. AIIRA, P = NS). Aorta wall thickness ratio was reduced by AIIRA at 21 and 24 months vs. age-matched controls (21 months 0. 12 +/- 0.01 vs. 0.15 +/- 0.01, P = 0.006; 24 months 0.10 +/- 0.005 vs. 0.14 +/- 0.003, AIIRA vs. controls, respectively, P = 0.0027). The aorta wall thickness ratio after treatment with AIIRA for six months was even lower than that of 18-month control rats (P = 0.018). AIIRA reduced proteinuria versus age-matched control at 24 months (253 +/- 62 vs. 390 +/- 51 mg/24 h, P = 0.0017). AIIRA at 24 months decreased glomerulosclerosis versus age-matched control (sclerosis index, 0 to 4+ scale: 0.06 +/- 0.02 vs. 0.49 +/- 0.12, P = 0.0082) to levels even lower than the 18-month baseline (0.37 +/- 0.14, P = 0.014). Renal collagen content increased with aging and was decreased by AIIRA at 24 months (5.0 +/- 0.7 vs. 3.1 +/- 0.5% collagen, P < 0.05). Apoptosis, assessed by TUNEL, was increased in tubular and interstitial cells in aging and was reduced by AIIRA versus control and baseline, respectively (TUNEL scoring, AIIRA 24 months 0.33 +/- 0.16 vs. 1.06 +/- 0.23 and 0.80 +/- 0.05, P < 0.05). PAI-1 mRNA in kidney was decreased at 24 months in AIIRA versus age-matched controls (PAI-1/GAPDH density ratio: AIIRA 24 months 0. 34 +/- 0.05 vs. 24-month controls 0.99 +/- 0.05, P < 0.05). Increased glomerular PAI-1 immunostaining with aging was decreased by AIIRA at 24 months versus age-matched controls, even below baseline (staining score 0 to 4+, 0.57 +/- 0.15 vs. control 0.90 +/- 0.07, P < 0.05; baseline 1.05 +/- 0.02, P < 0.01). CONCLUSION: We conclude that AIIRA not only slows the progression of glomerular and vascular sclerosis in aging, but can also induce regression of these processes. The mechanisms appear to involve modulation of cortical cell turnover and inhibition of PAI-1 expression.     

Competing Risks Analysis of Predictors of Delisting Owing to Tumor Progression in Liver Transplant Candidates with Hepatocellular Carcinoma

Orthotopic liver transplantation (OLT) is potentially curative for patients with early stage hepatocellular carcinoma (HCC). However, tumor progression before OLT remains a problem. Ninety-three patients were listed for transplantation with HCC or diagnosed with HCC following listing between March, 1997 and September, 2001. Modified TNM Stage was I/II in 82 patients and III in 11 patients. Seventy-one patients (76%) were transplanted with a median waiting time of 3.4 months, and 22 (24%) patients were delisted owing to tumor progression (14), noncompliance (5), and death from liver failure (3). Using a cox model competing risks approach, higher baseline alpha-fetoprotein (AFP) >or= 100 ng/mL was the only factor independently associated with a higher hazard rate of delisting owing to tumor progression (p = 0.00003), whereas four separate factors were independently associated with a lower hazard rate of transplantation: more recent listing year (1999-2001, p = 0.010), blood type O (p = 0.013), Stage I HCC (p = 0.029), and serum bilirubin < 4 mg/dL (p = 0.032). By logistic regression, AFP >/= 100 ng/mL was the only factor that significantly influenced the probability of delisting owing to tumor progression (p = 0.001). In conclusion, the initial AFP level may be useful along with tumor stage in defining an urgency score for liver transplant candidates with HCC.     

肿瘤转移基因MTA 1在原发性肝癌中的表达及其临床意义

目的 了解肿瘤转移基因ＭＴＡ１在原发性肝癌转移复发中的作用。方法 利用反转录ＰＣＲ克隆出ＭＴＡ１编码区部分ｃＤＮＡ片段。对肝癌标本中ＭＴＡ１ｍＲＮＡ的表达情况进行原位杂交检测。结果 在伴有门静脉癌栓、肝内子灶、肝外转移、直径〉５ｃｍ,以及术后１年内死亡患者的肝癌中,ＭＴＡ１ｍＲＮＡ表达量显著增高（Ｐ〈０．０５）;而患者的性别、肝硬化情况及ＡＦＰ水平等与其表达水平无关。在部分侵袭性肝癌中,ＭＴＡ１ｍＲＮＡ阳性细胞集中分布于肿瘤边缘。结论 ＭＴＡ１基因表达量的增高与原发性肝癌的转移表型密切相关。可能在肝癌转移复发过程中具有重要作用。对肝癌的预后判断可能也具有一定意义。     

Measurement of serum circulating intercellular adhesion molecule-1 and its clinical significance in hepatocellular carcinoma: preliminary report

Serum circulating intercellular adhesion molecule-1 (cICAM-1) was measured in 50 patients with hepatocellular carcinoma (HCC). The mean cICAM-1 level in the 50 patients was 2220 ng/ml and 43 patients (86%) had a high level of cICAM-1 — more than 1000 ng/ml. Comparative analysis of cICAM-1 and alpha-fetoprotein (AFP) levels in the HCC patients showed that serum AFP level was negative (<20 ng/ml) in five patients or "questionable positive" (20–90 ng/ml) in ten patients, while the levels of cICAM-1 in these patients were 1810 and 1710 ng/ml, respectively. Seven patients who underwent hepatectomy had tumor recurrences during a follow-up period of 6–18 months. Their serum AFP levels were lower than 200 ng/ml (mean value, 27 ng/ml), but their mean cICAM-1 level was 1956 ng/ml at the time tumor recurrence was diagnosed. We suggest that the measurement of serum cICAM-1 is not only useful for prediction of the progression and prognosis of HCC, but that it may also be an important marker for the early diagnosis of the disease, and for monitoring postoperative recurrence, particularly in patients with low levels of serum AFP. Received for publication on Aug. 24, 1998; accepted on Jan. 4, 1999     

Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects

Low plasma fibrinolytic activity in association with increased plasma plasminogen activator inhibitor 1 (PAI-1) levels has been linked to an increased risk of atherosclerosis in obesity and type 2 diabetes. We tested the hypothesis that troglitazone, which improves insulin sensitivity and lowers plasma insulin levels in insulin-resistant obese subjects and patients with type 2 diabetes, would also lower circulating PAI-1 antigen concentrations and activity. We assessed insulin sensitivity (5-h, 80 mU x m(-2) x min(-1) hyperinsulinemic-euglycemic clamp) and measured plasma PAI-1 antigen and activities and tissue plasminogen activator (tPA) in 14 patients with type 2 diabetes and 20 normal control subjects (10 lean, 10 obese) before and after 3 months of treatment with troglitazone (600 mg/day). At baseline, plasma PAI-1 antigen levels after an overnight fast were significantly higher in the obese (33.5 +/- 4.7 microg/l) and type 2 diabetic subjects (54.9 +/- 6.3 microg/l) than in the lean control subjects (16.3 +/- 3.2 microg/l; P < 0.01 and P < 0.001, respectively). Troglitazone decreased plasma PAI-1 antigen concentrations in the diabetic patients (36.8 +/- 5.0 microg/l; P < 0.001 vs. baseline), but the reduction in the obese subjects did not reach statistical significance (baseline, 33.5 +/- 4.7; after troglitazone, 25.6 +/- 5.2 microg/l). Changes in plasma PAI-1 activity paralleled those of PAI-1 antigen. The extent of the reduction in plasma PAI-1 antigen concentrations in the diabetic patients after troglitazone correlated with the reductions in fasting plasma insulin (r = 0.60, P < 0.05), nonesterified fatty acid (r = 0.63, P < 0.02), and glucose concentrations (r = 0.64, P < 0.02) but not with the improvement in glucose disposal rates during the glucose clamps. Three nonresponders to troglitazone with respect to effects on insulin sensitivity and fasting glucose and insulin levels also had no reduction in circulating PAI-1. In conclusion, troglitazone enhances fibrinolytic system activity in insulin-resistant type 2 diabetic patients. This effect appears to be intimately linked to its potential to lower plasma insulin levels and improve glycemic control through its peripheral tissue insulin-sensitizing effects.     

循环肿瘤细胞对肝癌射频消融术后复发的预测价值

目的研究分析射频消融术(RFA)前循环肿瘤细胞(CTC)预测肝癌术后复发的应用价值。方法收集2016年6月至2019年9月中山市人民医院收治的168例肝细胞癌患者,在RFA治疗前以Cyttel检测法分析患者外周血的CTC。利用X-tile软件的Kaplan-Meier模块确定CTC的最佳临界值,并分析CTC与术前临床参数的关系,Cox比例风险模型分析影响RFA术后复发的独立危险因素,采用Kaplan-Meier法绘制RFA术后复发曲线图明确CTC与RFA术后复发的关系。结果预测肝癌RFA术后复发的CTC最佳临界值为2个/3.2 ml。术前CTC与肿瘤结节数目、最大肿瘤直径、术前AFP水平以及中国肝癌临床分期(CNLC)有关(P<0.05)。术前CTC(HR=1.965,95%CI:1.314~2.937,P=0.001)、AFP水平(HR=1.743,95%CI:1.158~2.623,P=0.008)、PIVKA-Ⅱ(HR=1.559,95%CI:1.008~2.411,P=0.046)以及最大肿瘤直径(HR=1.994,95%CI:1.104~3.602,P=0.022)均是肝癌RFA术后复发的独立危险因素。术后复发率62.5%(105/168),CTC≤2个/3.2 ml患者的累积复发率明显低于CTC>2个/3.2 ml者(P<0.001)。结论术前CTC检测对预测肝癌射频消融术后复发有一定的应用价值及临床意义。     

肝细胞癌患者血浆和癌组织中RASSF1A基因甲基化及临床意义

目的探讨肝细胞癌(hepatocellular carcimona,HCC)患者外周血浆和肿瘤组织中RASSF1A基因甲基化及其临床意义。方法应用甲基化特异性PCR(MSP)检测36例HCC患者血浆及其对应癌组织中的RASSF1A基因启动子甲基化状态,并分析其与临床参数的关系。结果癌组织和外周血浆中RASSF1A基因甲基化率分别为83.3%(30/36)和61.1%(22/36),二者相关系数为r=0.561(P=0.0004)。外周血浆和肿瘤组织中RASSF1A基因甲基化率与患者性别、年龄、HBV/HCV感染、肝硬化、肿瘤大小、AFP水平、肿瘤病理分级及临床分期、有无癌栓及是否为复发病例等之间无统计学相关性。以AFP≥400 ug/L为阳性,本组病例AFP阳性率为44.4%;以AFP≥20 ug/L为阳性,本组病例阳性率为69.4%。全部患者中,血浆RASSF1A基因甲基化检出率为61.1%,AFP联合血浆RASSF1A基因甲基化检测HCC的检出率为75%(27/36)。结论 HCC患者血浆和肿瘤组织中RASSF1A基因甲基化率有良好的一致性。血浆DNA甲基化联合AFP检测对HCC早期诊断具有一定意义。癌组织和血浆中基因甲基化改变与各临床参数无相关性。     

Impaired fibrinolytic activity in type II diabetes: correlation with urinary albumin excretion and progression of renal disease

Progression of renal disease and cardiovascular complications in type II diabetes mellitus have been shown to correlate with control of blood glucose, lipids, blood pressure, and smoking. These factors, however, do not appear to totally explain these diabetic complications. Renal disease and cardiovascular complications in type II diabetes are associated with vascular abnormalities and fibrosis, both of which may occur with impaired fibrinolysis. A cross-sectional study was therefore performed in 107 type II diabetic patients recruited from the Denver Metropolitan Area to examine the effect of impaired fibrinolysis, as assessed by the ratio of plasminogen activator inhibitor (PAI-1) to tissue-type plasminogen activator (t-PA). With urinary albumin excretion (UAE) as a risk factor for both renal disease progression and cardiovascular complications, the patients were analyzed with respect to UAE less than and greater than 1 gm/day. The age, blood glucose, hemoglobin A1C, duration of diabetes, lipids, body mass index, and smoking were no different between the groups. As expected, the group with greater UAE had worse renal function, the serum creatinine (1.98 +/- 0.24 vs 1.21 +/- 0.05 mg/dl, P < 0.001) and creatinine clearance (55.5 +/- 6.0 vs 76.8 +/- 2.7 ml/min, P < 0.001) were significantly different. The type II diabetic patients with greater UAE exhibited significantly higher PAI-1/t-PA (2.43 +/- 0.26 vs 1.85 +/- 0.07, P < 0.03). The past history of cardiac complications was also higher (87.5 vs 72.3%, P < 0.07) in the diabetic patients with more impaired fibrinolysis and greater UAE. Thus a prospective, randomized clinical trial in type II diabetes with PAI-1 inhibitors is needed.