纤溶酶原激活物抑制剂-1基因多态性与新生儿败血症易感性的关联

目的 探讨纤溶酶原激活物抑制剂-1(PAI-1)基因多态性与新生儿败血症易感性的关联。方法 选择承德医学院附属医院新生儿科2018年1月—2020年12月进行治疗的新生儿败血症患儿98例为病例组,随机选择同期医院新生儿科健康足月新生儿90例为对照组。通过血培养确定新生儿败血症感染病原菌种进行鉴定;检测外周血C-反应蛋白(CRP)和白细胞介素-6(IL-6)以及凝血功能指标抗凝血酶Ⅲ(AT-Ⅲ)、D-二聚体(DD)及血小板(PLT)水平;采用聚合酶链式扩增反应和一代测序法检测PAI基因rs1799768位点基因多态性。结果 98例血培养阳性败血症新生儿共检出革兰阳性菌84例,占85.71%,革兰阴性菌14例,占比14.29%,金黄色葡萄球菌、B族链球菌和粪肠球菌为检出率最高的病原菌。病例组4G/5G位点基因型频率高于对照组,差异具有统计学意义(P<0.05),两组4G/4G、5G/5G基因型及4G、5G等位基因频率比较,无统计学差异;革兰阴性菌感染与革兰阳性菌感染败血症新生儿PAI基因4G/5G位点基因型、等位基因分布比较,无统计学差异;三组PAI-1基因多态性CRP、IL-6、AT-Ⅲ、DD及PLT水平整体比较差异具有统计学意义(P<0.05);4G/5G型败血症患儿CRP、IL-6、DD水平高于其他两组,AT-Ⅲ、PLT水平低于其他两组,差异均具有统计学意义(P<0.05)。结论 PAI基因rs1799768位点4G/5G基因型显著增加新生儿败血症风险,但与感染病原类型无关,其机制可能与影响纤溶系统有关。     

兰州地区育龄期女性5,10-亚甲基四氢叶酸还原酶与纤溶酶原激活物抑制剂-1基因多态性研究

目的 探讨兰州市育龄期女性5,10-亚甲基四氢叶酸还原酶(MTHFR)与纤溶酶原激活物抑制剂-1(PAI-1)基因多态性的频率特征,指导围孕期妇女个性化用药。方法 通过荧光PCR技术,对兰州市1 836名育龄期女性进行MTHFR和PAI-1基因的遗传检测,分析MTHFR与PAI-1基因的多态性分布情况以及MTHFR两位点间连锁不平衡水平(LD),并和历年报道的各地区数据进行比较分析。结果 MTHFR 677基因CC、CT、TT基因型频率分别为26.6%、48.5%、24.9%,C、T等位基因频率分别为50.9%、49.1%。MTHFR 1298基因AA、AC、CC基因型频率分别为70.5%、26.5%、3.1%,A、C等位基因频率分别为83.7%、16.3%。PAI-1基因5G5G、5G4G、4G4G基因型频率分别为19.9%、47.9%、32.2%,5G、4G等位基因频率分别为43.9%、56.2%。单倍型分析共存在7种组合,频率最高的为CT/AA(33.1%),其次分别为TT/AA(24.7%)、CT/AC(15.4%)、CC/AA(12.6%)、CC/AC(10.9%)、CC/C...     

尿激酶型纤溶酶原激活物与子宫颈癌

在妇女的肿瘤病中，宫颈癌的发生率仅次于乳腺癌，位居第二位。全世界每年都有约20万妇女死于这种疾病。在发展中国家，宫颈癌的发生率是发达国家的6倍，而且80％的患者在确诊时已经发展为浸润癌。几十年来世界范围对宫颈癌的防治工作已取得显著成效。然而，与诸多其它恶性肿瘤相比，在宫颈癌肿瘤标志物的研究方面一直比较滞后。尿激酶型纤溶酶原激活物介导的纤溶系统与细胞外基质和基底膜的降解有关，在肿瘤的生长、浸润和转移过程中起重要作用。本文旨在检测尿激酶型纤溶酶原激活物的水平，来作为监测宫颈癌的浸润、转移及预后的新方法、新途径。     

糖化血红蛋白对糖尿病肾病早期患者纤溶酶原激活物抑制物1的影响

目的探讨糖化血红蛋白（GHbA1c）对糖尿病肾病（ON）早期患者组织型纤溶酶原激活物（t-PA）以及纤溶酶原激活物抑制物-1（PAI-1）活性的影响。方法2004年4月至2005年5月收治DN早期患者90例。根据GHbA1c水平分为3组,每组各30例。A组GHbA1c〈7％,B组GHbA1c7％-9％,c组GHbA1c〉9％,另选择健康体检者30例作为对照组。所有人选者在清晨空腹抽血测定GHbA1c、t-PA、PAI-1。结果与对照组比较,DN各组GHbA1c、t-PA、PAI-1差异均有统计学意义（P〈0．05或〈0．01）,其中t-PA活性下降,而PAI-1活性上升。C组与A组比较t-PA活性下降[分别为（0．14±0．06）、（0．28±0．11）U/ml],PAI-1活性上升[分别为（3．25±1．01）、（1．90±1．09）I／ml],差异均有统计学意义（P〈0．05）;而B组与A组比较t-PA活性有下降趋势,PAI-1活性有上升趋势,但差异均无统计学意义（P〉0．05）。结论DN早期患者体内存在着纤溶系统的失衡,持续高血糖状态进一步破坏纤溶系统,严格控制GHbA1c达标是延缓糖尿病及其并发症发生和发展的重要因素之一。     

尿激酶型纤溶酶原激活物与子宫颈癌

在妇女的肿瘤病中,宫颈癌的发生率仅次于乳腺癌,位居第二位。全世界每年都有约20万妇女死于这种疾病。在发展中国家,宫颈癌的发生率是发达国家的6倍,而且80%的患者在确诊时已经发展为浸润癌。几十年来世界范围对宫颈癌的防治工作已取得显著成效。然而,与诸多其它恶性肿瘤相比,在宫颈癌肿瘤标志物的研究方面一直比较滞后。尿激酶型纤溶酶原激活物介导的纤溶系统与细胞外基质和基底膜的降解有关,在肿瘤的生长、浸润和转移过程中起重要作用。本文旨在检测尿激酶型纤溶酶原激活物的水平,来作为监测宫颈癌的浸润、转移及预后的新方法、新途径。     

NIDDM患者血浆纤溶酶原激活物抑制剂-1(PAI-1)与并发冠心病关系的探讨

为明确血浆纤溶酶原激活物抑制剂－１（ＰＡＩ－１）在ＮＩＤＤＭ发生冠心病中所起的作用,并分析其影响因素。将６０例ＮＩＤＤＭ患者分为冠心病（ＣＡＤ）组和非ＣＡＤ组,用底物发光法检测血浆ＰＡＩ－１及组织型纤溶酶原（ｔ－ＰＡ）,同时检测血糖、血胰岛素、血脂等指标。结果表明：ＣＡＤ组血浆ＰＡＩ－１活性水平明显高于非ＣＡＤ组,分别为１０．０６±２．５与８．０８±２．６２,单位Ａｕ／ｍｌ,Ｐ＜０．０１。两组ｔ－ＰＡ相似。在ＣＡＤ组,血浆ＰＡＩ－１活性与空腹胰岛素、胰岛素敏感指数均相关,相关系数分别为０．２４（Ｐ＜０．０５）与－０．３（Ｐ＜０．０１）,且与甘油三酯呈正相关（ｒ＝０．２４,Ｐ＜０．０５）,和ＡｐｏＢ正相关（ｒ＝０．５１,Ｐ＜０．０５）。血浆ＰＡＩ－１活性水平的升高与ＮＩＤ－ＤＭ发生ＣＡＤ危险性存在相关。胰岛素抵抗状态、高胰岛素血症、高ＴＧ水平都可刺激血浆ＰＡＩ－１活性的升高,而高血糖对其无直接的作用。ＡｐｏＢ参与ＰＡＩ－１活性改变这一过程,并在ＣＡＤ发生中可能介导其它脂质异常刺激ＰＡＩ－１升高的作用。     

股骨颈骨折术后患者血清1型纤溶酶原激活物抑制剂、内皮素-1水平表达及与股骨头坏死发生的关系

目的 观察血清1型纤溶酶原激活物抑制剂(PAI-1)、内皮素-1(ET-1)水平在股骨颈骨折术后患者中的表达情况,并分析上述血清指标与股骨头坏死发生的关系。方法 纳入2014年4月—2021年6月在浙江省湖州市福音医院行手术治疗的96例股骨颈骨折患者作为研究对象,所有患者均在术后1 d测定血清PAI-1、ET-1水平,并以门诊复诊方式随访1年,统计随访期间患者股骨头坏死发生情况,将发生股骨头坏死的患者纳入病例组,反之纳入常规组,并采用SPSS 25.0软件分析股骨颈骨折术后患者血清PAI-1、ET-1水平表达与股骨头坏死发生的关系。结果 随访1年,96例股骨颈骨折术后患者中共有19例发生股骨头坏死,发生率为19.79%;病例组血清PAI-1、ET-1水平高于常规组,差异有统计学意义(P<0.05);经点二列相关分析证实,股骨颈骨折术后患者血清PAI-1、ET-1水平与股骨头坏死发生成正相关(r值分别为0.526、0.559,P<0.05);经多项logistic回归分析,结果显示,血清PAI-1、ET-1水平升高是股骨颈骨折术后患者股骨头坏死发生的危险因素(P<0.0...     

尿激酶型纤溶酶原激活系统在子宫内膜癌中的表达及意义

目的:研究uPA系统在子宫内膜癌发生、发展、浸润、转移中的作用及其对临床诊断、治疗及预后的指导意义。方法:应用免疫组织化学方法测定正常子宫内膜、增生子宫内膜及子宫内膜癌组织中uPA系统的表达。结果:uPA系统在子宫内膜癌组织中的表达显著高于增生子宫内膜组织及正常子宫内膜组织,而在增生子宫内膜组织与子宫内膜正常组织中的表达则无显著性差异;子宫内膜癌组织中uPA系统的表达与其手术-病理分期和组织学分级、肌层浸润深度、是否出现淋巴结转移有关;uPA与uPAR及PAI-1的表达呈正相关。结论:uPA系统与子宫内膜癌的发生、发展、浸润、转移密切相关,且其各因子在此过程中起着相互协同、互相调节的作用。     

A low-glycemic-index diet reduces plasma plasminogen activator inhibitor-1 activity, but not tissue inhibitor of proteinases-1 or plasminogen activator inhibitor-1 protein, in overweight women

BACKGROUND: The development of obesity has been suggested to involve plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of proteinases-1 (TIMP-1). Plasma PAI-1 is elevated in obesity. A low-glycemic-index (LGI) diet may have a beneficial effect on obesity through a decrease in plasma PAI-1, but whether it affects plasma TIMP-1 in healthy humans has not been studied. OBJECTIVE: We investigated whether a 10-wk intake of an LGI or a high-glycemic-index (HGI), high-carbohydrate, low-fat, ad libitum diet is associated with decreases in plasma PAI-1 and TIMP-1 concentrations in overweight women. DESIGN: Forty-four overweight women [body mass index (BMI; in kg/m2): 27.5+/-0.23] were randomly assigned to consume an HGI or an LGI diet for 10 wk. A subgroup of 29 women was assigned to participate in an additional 4-h meal test on the last day of the 10-wk intervention. RESULTS: PAI-1 activity decreased after 10 wk of the LGI diet and was significantly different between groups. Changes in PAI-1 antigen followed the same trend, but no significant difference was observed between groups. No difference in plasma TIMP-1 concentrations was observed between groups. PAI-1 and TIMP-1 concentrations after the 4-h meal test were not significantly different between groups. CONCLUSION: An LGI diet reduces fasting plasma PAI-1 activity and therefore may be useful for diminishing the adverse cardiovascular effects of obesity. This trial was registered at clinicaltrials.gov as NCT00324090.     

Reduced plasminogen activator content of the endometrium in oral contraceptive users

Human endometrium was found to contain two different plasminogen activators, urokinase and tissue activator. Urokinase was released in higher amounts from endometrial tissue explants obtained in the midcycle phase than from those obtained in the luteal phase. Plasminogen activator activity of the culture medium followed the same pattern.Treatment of postmenopausal patients with ethinylestradiol resulted in liberation of urokinase and tissue activator from endometrial explants in concentrations similar to those found in the normal midcycle phase. In contrast, treatment with oral contraceptives (OCs), containing ethinylestradiol and a progestagen, resulted in lowered release of both activators, even lower than was found during the normal luteal phase. Also the amounts of extractable urokinase from endometrial tissue samples were significantly lower in OC-users than in non-users.Estradiol seems to have a stimulatory effect on the release of plasminogen activators from the endometrium; whereas, gestagens depress the content and release of activators.The low content of plasminogen activators in the endometrium explains the reduced menstrual bleedings found in OC-users.     

Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk

Although oral contraceptives are protective for ovarian cancer, it is unclear how long this protection persists. The authors prospectively assessed this question as well as associations of other, less studied contraceptive methods (tubal ligation, rhythm method, diaphragm, condoms, intrauterine device, foam, spousal vasectomy) and infertility with ovarian cancer risk among 107,900 participants in the US Nurses' Health Study. During 28 years of follow-up (1976-2004), 612 cases of invasive epithelial ovarian cancer were confirmed. Duration of oral contraceptive use was inversely associated with risk (p-trend = 0.02), but no clear trend was observed for years since last use. However, for women using oral contraceptives for >5 years, the rate ratio for ovarian cancer for 20 years since last use (rate ratio (RR) = 0.92, 95% CI: 0.61, 1.39). Tubal ligation (RR = 0.66, 95% CI: 0.50, 0.87) was associated with decreased ovarian cancer risk, whereas intrauterine device use (RR = 1.76, 95% CI: 1.08, 2.85) and infertility (RR = 1.36, 95% CI: 1.07, 1.75) were associated with an increased risk. Results suggest that the beneficial effect of oral contraceptives on ovarian cancer risk attenuates after 20 years since last use. Furthermore, tubal ligation, intrauterine device use, and infertility were associated with ovarian cancer risk.     

绿茶多酚对纤溶酶原激活物抑制剂-1表达影响

目的 观察绿茶多酚(GTPs)对牛主动脉内皮细胞(BAECs)纤溶酶原激活物抑制剂-1(PAI-1)表达的影响。方法 采用蛋白免疫印迹(Western blot)检测细胞中PAI-1表达水平,酶联免疫吸附实验(ELISA)检测细胞培养液中PAI-1含量。结果 GTPs可使BAECs中PAI-1的表达和释放降低,且呈一定的时间和浓度依赖性。其中GTPs作用4 h时PAI-1表达开始显著降低(P<0.05),至作用8 h时抑制PAI-1表达最为明显(P<0.05)。随着GTPs浓度的升高,抑制效应增强,40μg/ml GTPs的抑制作用最为明显(P<0.05)。结论 GTPs可以抑制BAECs中PAI-1的表达和释放,可能具有一定的调节纤溶系统活性的功能。     

二氧化硅对人肺泡Ⅱ型上皮细胞纤溶酶原激活物抑制因子-1和激活蛋白-1表达的影响

目的研究SiO2对人肺泡Ⅱ型上皮细胞(A549)中纤溶酶原激活物抑制因子1(PAI1)及激活蛋白1(AP1)表达的影响,探讨SiO2致肺纤维化的发病机制。方法按SiO2(200μg/ml)与A549细胞共育时间的不同,实验分SiO2刺激0、4、8、16、24h组。利用逆转录聚合酶链反应(RTPCR)、Westernblot及免疫细胞化学SP法检测细胞PAI1mRNA和蛋白的表达;AP1(cjun/cfos)总蛋白及核蛋白表达的检测采用Westernblotting。结果SiO2刺激后,实验组PAI1mRNA及蛋白表达强度随时间延长依次增强,呈直线正相关(rmRNA=0.911,r蛋白=0.902,P<0.05),且实验组PAI1蛋白表达均高于对照组(0.36±0.03),其中24h组(0.73±0.01)表达最强;cjun和cfos核蛋白的表达亦明显高于对照组(0.52±0.02、0.15±0.01),cjun核蛋白的表达4h组(1.54±0.02)最强;cfos核蛋白表达8h组(0.36±0.01)最强;cjun和cfos核蛋白的表达均从孵育16h开始逐渐下降。AP1(cjun/cfos)总蛋白的表达各组间差异无统计学意义(P>0.05);PAI1阳性信号定位于胞浆和胞核。结论SiO2能够诱导A549细胞PAI1的表达,呈现出明显的时间-效应关系,核转录因子AP1在SiO2刺激的早期被激活。     

Vitamin D receptor gene polymorphism and bone metabolism during low-dose oral contraceptive use in young women

With the aim to determine whether bone metabolism in young women using low-dose oral contraception is influenced by vitamin D receptor (VDR) genotype, we designed the prospective clinical study of 41 healthy women aged 20-27 years. Twenty-one women of the study group were prescribed an oral contraceptive (30 microg ethynyl estradiol and 150 microg levonorgestrel) and 20 women of the control group a nonhormonal contraceptive or none. Biochemical markers of bone metabolism (bone-specific alkaline phosphatase, osteocalcin, deoxypyridinoline) and VDR genotype, using BsmI endonuclease, were determined. After 3 months in the study group, the BB genotype subgroup showed significantly decreased osteocalcin (p = 0.010), in the Bb genotype subgroup bone-specific alkaline phosphatase (p = 0.043) and osteocalcin (p = 0.006) decreased, and in the bb genotype subgroup no changes were observed. In the control group, there were no significant changes in markers of bone metabolism regarding VDR genotype. In conclusion, our study shows that in young women VDR gene polymorphism could influence bone metabolism during low-dose oral contraceptive use.     

Job strain and plasminogen activator inhibitor-1: results from the Swedish WOLF study

Objectives To investigate the association between job strain and elevated levels of plasminogen activator inhibitor-1.Methods A cross-sectional study was carried out, comprising 1,954 actively working men and women between the ages of 19–64 years. Data were collected by questionnaire, clinical examination and blood samples.Results Elevated plasminogen activator inhibitor-1 levels were more commonly noted in women exposed to job strain than in unexposed women (odds ratio 1.33; 95% confidence interval 1.06–1.65). This association remained after we had adjusted for factors related to behaviour and general health, but became close to 1 after we had adjusted for factors related to the metabolic syndrome. For men, no association between job strain and elevated levels of plasminogen activator inhibitor-1 was observed (odds ratio 0.94; 95% confidence interval 0.71–1.26).Conclusions Women exposed to job strain were more inclined to respond with increased plasminogen activator inhibitor-1 than men. In this first study on the association between job strain and plasminogen activator inhibitor-1 in both men and women, we observed such a relationship among women but not among men. The data support the notion that job strain might affect the risk of coronary heart disease by influencing an important cardiovascular system: the metabolic syndrome.     

Breast cancer and oral contraceptive use in Asian-American women.

Breast cancer incidence has historically been 4-7 times higher in the United States than in Asia. A previous study by the authors in Asian-American women demonstrated a substantial increase in breast cancer risk in women who migrated from Asia to the United States, with the risk almost doubling during the first decade after migration. Increased use of oral contraceptives soon after migration to the United States could possibly explain this rapid rise in risk. In a population-based case-control study of Chinese, Filipino, and Japanese-American women, aged 20-55 years, who lived in San Francisco-Oakland, California; Los Angeles, California; and Oahu, Hawaii during 1983-1987, 597 cases (70% of those eligible) and 966 controls (75%) were interviewed. Controls were matched to cases on age, ethnicity, and area of residence. Oral contraceptive (OC) use increased with time since migration; 15.0% of Asian-born women who had been in the West <8 years, 33.4% of Asian-born women who had been in the West > or =8 years, and 49.6% of Asian women born in the West had ever used OCs. However, duration of OC use (adjusted for age, ethnicity, study area, years since migration, education, family history of breast cancer and age at first full-term birth) was not associated with increased risk of breast cancer. Moreover, neither OC use before age 25 years nor before first full-term birth was associated with increased risk. Results were unchanged when restricted to women under age 45 years or under age 40 years. After adjustment for duration of OC use, women who had been in the United States > or =8 years were still at almost twice the risk of breast cancer compared with women who had been in the United States 2-7 years. This study suggests that OC use cannot explain the elevated risk observed in Asian women who migrated to the United States > or =7 years ago.     

Short-term oral contraceptive use and the risk of epithelial ovarian cancer

Oral contraceptive (OC) use has been consistently linked to a reduction in ovarian cancer in a dose-dependent fashion. Whether short-term OC use is protective remains controversial. In 1994-1998 in the Delaware Valley of Pennsylvania, the authors examined the association between short-term OC use and ovarian cancer in a population-based case-control study comparing 608 incident epithelial ovarian cancer cases with 926 community controls. Using unconditional logistic regression and adjusting for known confounders, they found a significant reduction in ovarian cancer risk for women who had used OCs for < or =6 months (odds ratio = 0.73, 95% confidence interval: 0.54, 0.99). This protective effect was observed in only that group who had used OCs for < or =6 months and stopped because of side effects (odds ratio = 0.59, 95% confidence interval: 0.40, 0.87 for side effects and odds ratio = 0.91, 95% confidence interval: 0.60, 1.37 for non-side-effects). Women who used OCs for >6 months were at a reduced risk independent of their reason for stopping. Results were similar when stratifying by parity and hormone therapy use. Thus, OC use for as little as 6 months provides significant protection against ovarian cancer risk, protection that appears limited to those women who stop using OCs because of side effects. Mediating factors may reflect endogenous hormone levels, OC metabolism, or OC bioactivity.