PCNA、ER和PR在子宫内膜癌中的表达

目的：探讨PCNA、ER和PR在子宫内膜癌发生、发展中的作用,对子宫内膜癌的诊断、治疗及预后提供一定的理论依据。方法：SP法检测正常子宫内膜组织、增生期子宫内膜组织、不典型增生子宫内膜组织及子宫内膜癌组织中PCNA、ER和PR蛋白的表达变化,统计分析各组间PCNA、ER和PR表达变化与临床因素及病理特征间的关系,以及各指标间的相关性。结果：①子宫内膜癌组织中PCNA表达阳性率为89．47％,显著高于正常子宫内膜组、子宫内膜单纯或复杂型增生组和子宫内膜不典型增生组（P〈0．01,P〈0．01,P〈0．01）。②子宫内膜癌组织中ER表达阳性率为54．74％,显著低于正常子宫内膜组、子宫内膜单纯或复杂型增生组（P〈0．01,P〈0．01）,与子宫内膜不典型增生组无统计学意义（P〉0．05）。⑧子宫内膜癌组织中PR表达阳性率为62．Ii％,显著低于正常子宫内膜组、子宫内膜单纯或复杂型增生组（P〈0．01,P〈0．01）,与子宫内膜不典型增生组无统计学意义（P〉0．05）。④子宫内膜癌组织中PCNA、ER和PR的表达与患者年龄无相关性;PR的表达与临床分期有相关性（P〈0．05）,与病理分级、淋巴结转移和肌层浸润深度无相关性;而PCNA、ER的表达与临床分期、病理分级、淋巴结转移以及肌层浸润深度有均无相关性。结论：子宫内膜癌中PCNA表达增加,ER和PR表达降低,PCNA、ER和PR参与了子宫内膜癌的发生与发展。PR在子宫内膜癌的侵袭和转移中起作用。联合检测PCNA、ER和PR的表达可以为临床治疗子宫内膜癌提供重要依据。     

C-erB-2、ER、PR在子宫内膜癌中的表达及意义

目的 探讨雌激素受体(ER)、孕激素受体(PR)及第二人体表皮生长因子受体(C-erB-2)在子宫内膜癌中的表达及意义.方法 应用免疫组化SP法检测三者在30例正常子宫内膜、30例子宫内膜息肉及86例子宫内膜癌组织中的表达水平,分析其临床意义及相关性,并将其与子宫内膜癌手术病理分期、组织细胞学分化程度、肌层浸润深度、淋巴结转移等高危因素进行分析.结果 (1) C-erB-2、ER及PR在正常子宫内膜、子宫内膜息肉和子宫内膜癌中的阳性表达率组与组之间差异均有统计学意义(P＜0.05).(2) C-erB-2阳性表达与手术病理分期、组织细胞学分级及淋巴结转移相关(P＜0.05);ER阳性表达与手术病理分期、组织细胞学分级及肌层浸润相关(P＜0.05);PR与组织细胞学分级、肌层浸润及淋巴结转移相关(P＜0.05).(3)C-erB-2与ER的表达呈负相关(r=-0.247,P＜0.05),ER与PR的表达呈正相关(r=0.756,P＜0.05).结论 在子宫内膜癌中,C-erB-2、ER及PR 联合检测可作为早期诊断、指导内分泌治疗及判断预后的重要指标.     

子宫内膜癌中Maspin、uPA、ER、PR的表达及临床意义

目的 探讨子宫内膜癌中Maspin蛋白、uPA蛋白及雌激素受体(ER)、孕激素受体(PR)间表达的相关性及临床意义.方法 对2004年6月至2014年6月病理科存档的蜡块,子宫内膜癌50例、不典型增生的子宫内膜50例及正常增殖期子宫内膜30例,采用免疫组化SP法,检测Maspin蛋白、uPA蛋白、ER、PR的表达情况,结合临床病理特征分析4种蛋白间表达的相关性.结果 Maspin蛋白、ER、PR在增殖期子宫内膜,不典型增生的子宫内膜,子宫内膜癌中阳性表达率逐渐降低,且组间比较有统计学意义(P＜0.05),而uPA的阳性表达率逐渐升高(P＜0.05).Maspin、uPA、ER、PR的阳性表达率在手术病理分期、肌层浸润深度及有无淋巴结转移组中的差异均有统计学意义(P＜0.05).Maspin和ER、PR的表达呈一致性,Maspin与uPA呈负相关(r=-0.341,P＜0.05),uPA和ER呈负相关(r=-0.293,P＜0.05).结论 ER、PR的减少,Maspin蛋白表达的缺失,伴随uPA蛋白表达上调,四者均参与了子宫内膜癌的发生、发展、浸润等过程,有可能成为判断子宫内膜癌治疗及预后的指标.     

引起月经异常的子宫内膜息肉雌孕激素受体表达的研究

目的 检测有月经异常的子宫内膜息肉患者子宫内膜息肉组织中雌激素受体(ER)、孕激素受体(PR)的表达,探讨子宫内膜息肉的发病机制及子宫内膜息肉引起月经异常的机制.方法 选择在淄博市妇幼保健院妇科就诊的患者,有月经异常组55例,无月经异常组45例以及无子宫内膜息肉的对照组36例,采用免疫组织化学方法测定ER和PR在三组中的表达,并对三组患者的ER和PR进行比较.结果 三组患者ER均呈强阳性表达,差异无统计学意义(P＞0.05).有月经异常组中PR呈弱阳性表达,无月经异常组中PR呈中等阳性表达,对照组中PR呈强阳性表达.三组患者间PR比较差异均有统计学意义(P＜0.05).结论 PR在子宫内膜息肉上的低表达可能是息肉形成以及出现子宫内膜息肉出血的原因之一.     

芳香化酶P450在子宫内膜增殖及非典型增殖组织中的表达

目的探讨芳香化酶P450在子宫内膜增殖和非典型增殖中的诊断和治疗价值。方法应用免疫组织化学SP法对子宫内膜单纯性增殖30例、复杂性增殖32例及非典型增殖54例中的芳香化酶P450、雌激素受体(ER)及孕激素受体(PR)的表达进行检测,并结合临床过程进行分析。结果在正常增生期子宫内膜组织中无芳香化酶P450的表达,子宫内膜增殖(单纯性增殖、复杂性增殖、非典型增殖)组织中芳香化酶P450呈阳性表达,阳性表达率分别为41.1%、46.1%、73.2%,阳性表达率差异有统计学意义(χ2=46.69,P<0.01);ER及PR的表达与子宫内膜组织细胞的异型性程度无关;芳香化酶P450与ER、PR在子宫内膜增殖组织中(单纯性增殖、复杂性增殖、非典型增殖)的表达不存在相关性。结论芳香化酶P450可能是子宫内膜细胞增殖及恶变的促进因素之一,并可能成为子宫内膜早期癌变的生物学标记物。ER的阳性表达说明子宫内膜增殖的发生与子宫内膜局部雌激素的刺激作用有关。PR的阳性表达可以作为子宫内膜增殖保守治疗中估计预后的有效指标。     

雌激素受体、孕激素受体、p53蛋白、p16蛋白在子宫内膜癌组织中的表达及其临床意义

目的探讨雌激素受体(ER)、孕激素受体(PR)、p53蛋白(p53)、p16蛋白(p16)在子宫内膜癌组织中的表达及其临床意义。方法选取2017年1月至2021年5月于滁州市第一人民医院住院切除的子宫内膜癌组织57例作为研究组, 选取30例子宫内膜增生症患者的周围正常子宫内膜组织作为对照组。采用Envision法免疫组化染色, 观察ER、PR、p53、p16在子宫内膜组织中的表达及其与临床病理学特征间的关系。结果子宫内膜癌组ER、PR、p16的阳性表达率分别为70.2%、61.4%、38.6%, 均低于对照组的90.0%、86.7%、93.3%(χ2=4.36、5.98、24.09, 均P < 0.05);p53在子宫内膜癌组阳性表达率52.6%、明显高于对照组的13.3%(χ2=12.75, P < 0.001);有无淋巴结转移、肌层浸润程度、组织分级、病理分期等子宫内膜癌患者的ER、PR表达差异均有统计学意义(均P < 0.05);p53在病理分期、发病年龄、组织分级、肌层浸润程度、淋巴结转移中差异均无统计学意义(均P > 0.05);p16阳性表达率在子宫...     

雌激素受体α、β及细胞周期蛋白D1、癌基因蛋白质P21 在子宫内膜癌组织中的表达及临床意义

目的 探讨雌激素受体α(ERα)、β(ERβ)及细胞周期调控因子CyclinD1、P21在子宫内膜癌组织中的蛋白表达水平及相关的临床意义。方法 选取徐州市中心医院2016年1月至2017年12月65例子宫内膜癌组织、30例子宫内膜不典型增生组织以及30例正常子宫内膜组织,利用免疫组织化学染色检测各组组织中ERα、ERβ、CyclinD1和P21的蛋白表达水平。结果 ERα、ERβ、CyclinD1和P21蛋白在子宫内膜癌(47.69%、32.31%、76.92%、49.23%)、子宫内膜不典型增生(90.00%、46.67%、43.33%、66.67%)和正常子宫内膜(73.33%、63.33%、13.33%、96.67%)三组间的阳性表达率均差异有统计学意义(P＜0.05)。ERα在子宫内膜不典型增生组织中阳性表达率最高,ERβ和P21在正常子宫内膜组织中阳性表达率最高,CyclinD1在子宫内膜癌组织中阳性表达率最高。在子宫内膜癌组织中,ERα在Ⅲ-Ⅳ期、低分化、肌层浸润深度≥1/2以及有淋巴结转移的组织中阳性表达率降低(P＜0.05);ERβ在Ⅲ-Ⅳ期组织中的阳性表达率低于Ⅰ-Ⅱ期病人(P＜0.05);CyclinD1在低分化和肌层浸润深度≥1/2的组织中具有较高的阳性表达率(P＜0.05);而P21在Ⅰ-Ⅱ期、高中分化以及肌层浸润深度＜1/2的组织中具有较高的阳性表达率。结论 ERα和ERβ可能在子宫内膜癌形成及进展过程中发挥不同的作用,CyclinD1在子宫内膜癌中可能发挥促进癌症形成及进展的作用,P21在子宫内膜癌中则可能发挥抑制癌症形成及进展的作用。     

子宫腺肌病组织中ER、PR和EGFR的表达及其临床意义

目的探讨雌激素受体、孕激素受体、表皮生长因子受体在子宫腺肌病组织中的表达情况以及ER、PR、EGFR与AM发病的关系。方法采用免疫组化SP法检测40例子宫腺肌病患者异位内膜、在位内膜及40例正常子宫内膜组织中ER、PR、EGFR的表达。结果腺肌病组异位内膜、在位内膜组织中ER、PR表达水平显著低于正常子宫内膜,异位内膜组织中ER、PR表达无周期性变化,而在位内膜和正常子宫内膜组织中ER、PR表达均符合增生期高于分泌期的变化规律。腺肌病组异位内膜、在位内膜组织中EGFR的表达水平显著高于正常子宫内膜,并且在位内膜组织中EGFR的表达水平显著高于异位内膜。结论子宫腺肌病患者异位内膜组织中ER、PR的表达水平低,可能是其对抗激素药物治疗反应差的原因。子宫腺肌病患者异位内膜、在位内膜组织中EGFR表达水平增强,提示EGFR在子宫腺肌病的发生发展中起着重要作用,可能为靶向生物治疗提供一个新的靶点。     

米非司酮对子宫肌瘤组织中bcl-2、P53和雌、孕激素受体的影响

目的研究米非司酮对子宫肿瘤细胞内凋亡调控基因bcl-2、P53和雌激素受体(ER)、孕激素受体(PR)表达的影响.方法应用免疫组化技术测定12例经米非司酮治疗的子宫肌瘤组织中bcl-2、P53和ER、PR的阳性表达率,并以12例未用药的子宫肌瘤患者作对照.结果服药组子宫肌瘤组织中bcl-2、PR、ER阳性表达率较对照组显著下降(P＜0.01),P53阳性表达率两组差异无显著性(P＞0.05).结论米非司酮可明显降低肌瘤组织中ER、PR,而且可以抑制肌瘤细胞内bcl-2表达,从而诱导子宫肌瘤平滑肌细胞凋亡.     

雌激素受体、孕激素受体与凋亡基因蛋白在子宫腺肌症中的表达

目的探讨雌激素受体（ER）、孕激素受体（PR）及凋亡基因蛋白（bcl-2）在子宫腺肌症中正位及异位内膜的表达及意义。方法采用免疫组化PV-9000二步法检测20例正常子宫内膜,58例子宫腺肌症正位及异位内膜ER、PR和bcl-2的表达情况。结果子宫腺肌症病例中,正位和异位内膜组织中ER、PR、Bcl-2都有阳性表达,异位腺体上皮阳性率高于间质细胞（P〈0．05）,异位内膜Bcl-2阳性表达率高于正位内膜（P〈0．05）;且增生期阳性表达率高于分泌期,差异有显著性（P〈0．05）。子宫腺肌症病例正位和异位内膜中ER、PR阳性表达率差异无显著性（P〉0．05）,在异位内膜中ER、PR、bcl-2的表达具有相关性（P〈0．01）。结论子宫腺肌症正位和异位子宫内膜中均有ER、PR和bcl-2的阳性表达,提示可能与子宫腺肌症的发生发展有关。     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate, eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol

Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the beta(2)-adrenoceptor agonist formoterol [eformoterol]. This isomer contains two chiral centres and is being developed as an inhaled preparation for the treatment of respiratory disorders. Sepracor believes that arformoterol has the potential to be a once-daily therapy with a rapid onset of action and a duration of effect exceeding 12 hours. In 1995, Sepracor acquired New England Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the purpose of preparing formulations of levosalbutamol and arformoterol. Phase II dose-ranging clinical studies of arformoterol as a longer-acting, complementary bronchodilator were completed successfully in the fourth quarter of 2000. Phase III trials of arformoterol began in September 2001. The indications for the drug appeared to be asthma and chronic obstructive pulmonary disease (COPD). However, an update of the pharmaceutical product information on the Sepracor website in September 2003 listed COPD maintenance therapy as the only indication for arformoterol. In October 2002, Sepracor stated that two pivotal phase III studies were ongoing in 1600 patients. Sepracor estimates that its NDA submission for arformoterol, which is projected for the first half of 2004, will include approximately 3000 adult subjects. Sepracor stated in July 2003 that it had completed more than 100 preclinical studies and initiated or completed 15 clinical studies for arformoterol inhalation solution for the treatment of bronchospasm in patients with COPD. In addition, Sepracor stated that the two pivotal phase III studies in 1600 patients were still progressing. In 1995, European patents were granted to Sepracor for the use of arformoterol in the treatment of asthma, and the US patent application was pending.     

欧洲刺柏（Juniper）

活性成分与药理作用欧洲刺柏药用部位是其浆果，具有促水排泄、防腐、抗胃肠胀气和抗风湿作用，还可改善胃功能。用作促水排泄药可增加尿量（水丢失），但不增加钠排泄。成分萜品烯-4-醇可增加肾小球滤过率，但刺激肾。欧洲刺柏浆果对单纯疱疹病毒体外显示抗病毒活性，并具抗真菌活性。动物实验显示，欧洲刺柏浆果提取物具有堕胎、抗生育、抗炎、抗胚胎植入、降血压、升血压和降血糖作用。欧洲刺柏浆果油具有兴奋子宫的活性，以及利尿、胃肠道抗菌和刺激作用，该油对平滑肌有阻止解痉作用。     

Oral Presentations (LDD, LPES, LNM, LPAT, LNT, LPPT, LPM)

Probiotic microorganisms have been shown to provide specific health benefits when consumed as food supplements or as food components. The main problem of such products is the poor survival of the probiotic bacteria in the low pH of gastric fluid. However the use of synthetic excipients for enteric coating to prevent the exposure of microorganisms to gastric fluid is limited in food supplementary industry. Therefore the aim of this study was to develop an enteric coating formulation containing shellac as a natural polymer. Shellac possesses good resistance to gastric juice; the major disadvantage of this polymer is its low solubility in the intestinal fluid [1, 2]. Thus films containing different ratios of shellac and water-soluble polymers (sodium alginate, hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidon (PVP)) or plasticizers (glycerol and glyceryl triacetate (GTA)) were prepared in order to analyse the films’ melting temperatures (T_m), the changes in enthalpy (ΔH), their capability of taking up water, and their solubility in different media. The release characteristics of the films were studied by loading pellets with Enterococcus faecium M74 and coating them with formulations containing different amounts of shellac and polymer or plasticized shellac. Using dissolution tests, performed according to USP XXXI paddle method, the resistance of the coatings to simulated gastric fluid (SGF, pH 1.2) and the release of cells in simulated intestinal fluid (SIF, pH 6.8) was investigated.The trials showed that an increasing amount of plasticizer results in a decrease of T_m and ΔH of the films whereat glycerol had a superior plasticization effect to GTA. The compatibility of films made of water-soluble polymers and shellac was also concentration dependent. HPMC and PVP showed superior compatibility with shellac compared to sodium alginate, since films containing shellac and more than 10% [w/w] sodium alginate tended to separate into two phases. In the end five formulations containing shellac and either 5% [w/w] glycerol, 10% [w/w] PVP, 20% [w/w] PVP, 10% [w/w] HPMC, or 5% [w/w] sodium alginate emerged as feasible for enteric coating purposes.