Genistein Treatment Confers Protection against Gliopathy and Vasculopathy of the Diabetic Retina in Rats

Retinopathy remains an important complication of diabetes. This work was carried out to evaluate the protective effects of genistein from diabetic retinopathy in rat. Fifteen adult male albino rats were divided into two groups; Group I: control (n?=?5) and Group II: streptozotocin induced diabetic group (n?=?10), which is equally divided into two subgroups; IIa (diabetic vehicle control) and IIb (diabetic genistein-treated). Specimens were taken from the retina 12 weeks post induction, processed and examined using light, immunohistochemical, ultrastructural techniques. Blood samples were assayed for the levels of glucose. In comparison with the diabetic non-treated group, the histological changes in macro and microglial glial cells reactivity and retinal blood capillaries were improved in genistein-treated groups. In addition, GFAP and iNOS expressions in the retina and the blood glucose level were reduced. Genistein ameliorates the histological changes of diabetic retinopathy reaching healing features, which resemble that of a normal retina.     

无排卵型功血患者子宫内膜VEGF和雌、孕激素受体的表达

研究无排卵型功血患者子宫内膜血管内皮生长因子 (VEGF)、雌激素受体 (ER)和孕激素受体 (PR)的表达 ,探讨其与子宫内膜血管形成的关系 ,以求从蛋白水平阐明无排卵型功血的出血机制。采用免疫组化方法 ,检测VEGF、ER和PR在 2 0例正常增殖期和 6 0例无排卵型功血患者子宫内膜的表达。选用微血管密度标记物CD34,测定子宫内膜微血管密度 (MVD)。无排卵型功血患者单纯性增生和复合性增生子宫内膜腺上皮VEGF蛋白和MVD明显低于正常增殖期 (P <0 0 5和P <0 0 1 ) ;而单纯性增生和复合性增生子宫内膜腺上皮PR蛋白明显高于正常增殖期 (P <0 0 5和P <0 0 1 )。相关分析显示 ,子宫内膜腺上皮VEGF与MVD呈显著性正相关 (r =0 6 6 6 ,P <0 0 5 ) ;与腺上皮PR呈显著性负相关 (r=- 0 6 2 9,P <0 0 5 )。正常增殖期内膜与功血增殖期内膜比较 ,腺上皮VEGF和PR蛋白差异无显著性意义。首次指出病理表现为单纯性增生和复合性增生的无排卵型功血患者 ,其子宫异常出血与子宫内膜VEGF和PR的表达失调有关。PR间接作用于无排卵型功血子宫内膜腺上皮VEGF ,使后者分泌减少 ,微血管形成障碍 ,临床表现为子宫不规则出血     

Enhanced Expression of Sodium Hydrogen Exchanger (NHE)-1, 2 and 4 in the Cervix of Ovariectomised Rats by Phytoestrogen Genistein

Restoring the pH of cervicovaginal fluid is important for the cervicovaginal health after menopause. Genistein, which is a widely consumed dietary health supplement to overcome the post-menopausal complications could help to restore the cervicovaginal fluid pH. We hypothesized that genistien effect involves changes in expression of NHE-1, 2 and 4 proteins and mRNAs in the cervix. This study investigated effect of genistein on NHE-1, 2 and 4 protein and mRNA expression in the cervix in order to elucidate the mechanisms underlying possible effect of this compound on cervicovaginal fluid pH after menopause. Methods: Ovariectomised adult female rats received 25, 50 and 100 mg/kg/day genistein for seven consecutive days. At the end of the treatment, animals were sacrificed and cervix was harvested. Expression of Nhe-1, 2 and 4 mRNA were analyzed by Real-time PCR while distribution of NHE-1, 2 and 4 protein were observed by immunohistochemistry. Results: Treatment with 50 and 100 mg/kg/day genistein caused marked increase in the levels of expression and distribution of NHE-1, 2 and 4 proteins in the endocervical epithelia. Levels of Nhe-1, 2 and 4 mRNA in the cervix were also increased. Coadministration of ICI 182 780 and genistein reduced the expression levels of NHE-1, 2 and 4 proteins and mRNAs in the cervix. Conclusions: Enhanced expression of NHE-1, 2 and 4 proteins and mRNAs expression in cervix under genistein influence could help to restore the cervicovaginal fluid pH that might help to prevent cervicovaginal complications related to menopause.     

急性肺损伤大鼠血浆及支气管肺泡灌洗液中apelin含量的变化

目的:观察急性肺损伤大鼠血浆及支气管肺泡灌洗液(BALF)中apelin含量的变化,探讨apelin在急性肺损伤(ALI)中的意义。方法:雄性Wistar大鼠18只,随机分为对照组(n=8)和油酸模型组(n=10),油酸组尾静脉一次性注入油酸0.2ml/kg,对照组尾静脉内注射生理盐水0.2ml/kg。检测BALF中蛋白含量及中性粒细胞比例,放免法检测血浆及BALF中apelin-36含量。结果:①油酸组BALF中细胞计数、蛋白含量及中性粒细胞占细胞总数的百分比均显著高于对照组(P均<0.01);②油酸组血浆及BALF中apelin-36含量较对照组显著升高(P均<0.01)。结论:ALI时大鼠血浆及BALF中apelin-36含量升高。     

Morphological Estimation of Brain Extracellular Fluid Dynamics in Cold-induced Edema from the Aspect of Cerebrospinal Fluid-Extracellular Fluid Communication

Following the induction of cold injury in the parietal cortex of rats, the brain extracellular fluid dynamics under conditions of cryogenic edema were investigated morphologically from the aspect of extracellular fluid (ECF)-cerebrospinal fluid (CSF) communication using horseradish peroxidase (HRP) injected into the cisterna magna as a marker. About 24 h after the induction of cold injury, HRP was distributed in the subjacent white matter of the lesion and around the ventricle. Forty-eight hours after injury, the distribution of HRP around the lesion became distinctive. This distribution of HRP became more concentrated at the same location on day 3–4 after injury. At this time, HRP was observed to be distributed along the walls of small vessels, in the cytoplasm of a few neurons and in the neuropil around the lesion by light microscopy. At small vessels around the lesion, a dense deposit of HRP at the basement membrane and many abluminal vesicles were evident by electron microscopy. These findings indicate that ECF-CSF communication changes drastically under the influence of edema fluid dynamics. In particular, the dense distribution of HRP around the lesion on day 3–4 after injury can be attributed to active retrograde transport by vessels in this area, a phenomenon considered important for edema resolution.     

Clinical significance of histiocytes in the detection of endometrial adenocarcinoma and hyperplasia

The purpose of this case-control study was to determine the clinical significance of histiocytes and normal endometrial cells as cytologic markers of adenocarcinoma or hyperplasia of the endometrium. Cervical-vaginal smears obtained in 102 patients with mean age 59.7 yr with abnormal uterine bleeding and endometrial pathology, and 101 controls with mean age 56.5 yr with postmenopausal bleeding and whose cytologic smear was negative, were evaluated. Histiocytes alone failed to predict either endometrial adenocarcinoma (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.32–3.22) or hyperplasia (OR, 1.10; 95% CI, 0.37–3.30). The odds of endometrial carcinoma in symptomatic, postmenopausal women was three times greater in the presence of histiocytes with phagocytosis of acute inflammatory cells (PIC) (OR, 3.00; 95% CI, 1.16–7.70). Endometrial hyperplasia was more frequently observed when cervical smears contained normal endometrial cells (OR, 4.09; 95% CI, 1.14–14.67). Only histiocytes with PIC and normal endometrial cells carry a three- and fourfold greater likelihood of coexistent endometrial adenocarcinoma and hyperplasia, respectively. Such strong association may require endometrial biopsy or transvaginal ultrasonography to uncover lesional tissue in the endometrial cavity. Diagn. Cytopathol. 1998;19:89–93. © 1998 Wiley-Liss, Inc.     

Apoptosis and the expression of Bax and Bcl-2 in hyperplasia and adenocarcinoma of the uterine endometrium

BACKGROUND: Apoptosis plays a crucial role in carcinogenesis in various tumours. This study was designed to investigate the occurrence of apoptosis and the expression of Bcl-2 and Bax proteins in endometrial tumours of corpus uteri. METHODS: Endometrial tissues were obtained from 20 patients with endometrioid adenocarcinoma, 16 patients with endometrial hyperplasia, and 4 patients with myoma uteri (which were used as controls). The occurrence of apoptosis was examined by using molecular biochemical techniques. The expression of Bcl-2 and Bax proteins was also investigated using immunohistochemical staining with appropriate antibodies. RESULTS: The labelling of DNA in situ indicated that apoptotic cells were sporadically seen in postmenopausal endometrium (5.2 +/- 2.1, n = 4) and endometrial hyperplasia without atypia (2.6 +/- 0.5, n = 9). In contrast, labelled cells were detected in atypical endometrial hyperplasia (15.9 +/- 2.2, n = 7), and their numbers increased intensely in adenocarcinoma (29.3 +/- 3.7, n = 20). Autoradiographic analysis revealed DNA laddering in many cases of carcinoma. Bcl-2 was highly immunopositive in hyperplasia without atypia (36.2 +/- 6.5%, n = 9), but was decreased in the atypical endometrial hyperplasia (16.3 +/- 4.8%, n = 7). Large fractions of the carcinoma (6.3 +/- 1.8%, n = 20) and normal endometrium (2.8 +/- 1.4%, n = 4) were immunonegative or slightly immunopositive to Bcl-2. In contrast, Bax immunoreactivity was more frequent and stronger in adenocarcinoma (43.6 +/- 4.1%, n = 20) than that in normal endometrium (17.6 +/- 6.7%, n = 4) and hyperplasia (7.2 +/- 2.2%, n = 16). CONCLUSIONS: These results suggest that cells in hyperplasia expressing Bcl-2 might have prolonged survival ability. Neoplastic cells in adenocarcinoma might show apoptosis in association with a decreased expression of Bcl-2 and an increased expression of Bax. Therefore, the frequency of apoptosis and the expression of Bcl-2 and Bax might be correlated with carcinogenesis in the uterine endometrium of humans.     

宫颈腺上皮内粘多糖的组化改变与宫颈癌变的关系

用组化方法分析正常、非典型增生、原位癌和浸润癌4组宫颈腺体组织粘多糖变化。发现宫颈腺体中唾液酸粘多糖含量随癌变发展而增多,并探讨了这种改变的机理和意义。     

Implantation: The correlation of placental protein 14 concentrations in uterine flushing and endometrial morphology in the peri-implantation period

The relationship between the concentrations of placental protein14 (PP14) in uterine flushing and the endometrial morphologyin the mid-luteal phase was assessed in a prospectively designedstudy involving the precise timing of all samples by the luteinizinghormone (LH) surge. A total of 29 regularly cycling women withunexplained infertility or recurrent miscarriage were studied.To flush the uterine cavity, 10 ml of physiological saline solutionwas used immediately prior to sampling of an endometrial specimenfor morphological study, in the mid-luteal phase. PP14 concentrationswere measured by radioimmunoassay in uterine flushings and plasmasamples; the endometrium was assessed by the use of histologicaldating criteria and morphometric techniques. PP14 levels inuterine flushings were correlated with endometrial dating andvolume fraction measurement of the glands. They were consistentlybelow the sensitivity of the assay with histological datingof < day LH +5, or when the glandular lumen occupied <20%of the gland. In contrast, PP14 concentrations in plasma werenot related to histological dating or morphometric analyses,and did not differ in patients with normal endometrial development(20.8 ng/ml) and in those with retarded endometrial development(22.5 ng/ml). The presence of detectable concentrations of PP14in uterine flushing was significantly associated with normalhistological dating. Uterine flushing may therefore providea reliable, non-invasive alternative to endometrial biopsy inthe evaluation of endometrial function in the peri-implantationperiod.     

APA-BCC镇痛微囊在癌痛患者脑脊液中的生物学变化

了解海藻酸钙-多聚赖氨酸-海藻酸钙微囊化牛肾上腺嗜铬细胞(APA-BCC微囊)植入癌痛患者脑脊液中的形态、活率及亮氨酸脑啡肽(L-EK)分泌的变化。将APA-BCC微囊按常规腰穿方法植入癌痛患者蛛网膜下腔。7或8天时采取脑脊液,观察APA-BCC的形态、细胞活率,用放射免疫法测定脑脊液中L—EK的含量。移植7天后,患者视觉模拟疼痛评分(VAS)均值由移植前的8．8降为2．4;脑脊液中APA—BCC微囊形态无明显变化;细胞活率由平均91．2％降为89．1％;L-EK含量较移植前增加了1．65倍。将APA-BCC微囊植入癌痛病人脑脊液中能够保持细胞存活、分泌亮啡肽,并产生镇痛效应。     

Genistein调节肝癌HepG2细胞Caspase3蛋白表达诱导凋亡的作用研究

目的探讨三磷酸肌醇（IP3）和Caspase3蛋白表达变化在genistein诱导肝癌细胞凋亡中的作用。方法以肝癌HepG2细胞培养72h为对照组,实验各组以60μmol/L的genistein作用于HepG2细胞不同时间后,应用同位素试剂盒检测细胞IP3含量,Westernblotting分析细胞Caspase3蛋白表达,流式细胞仪检测细胞凋亡率。结果Genistein作用于肝癌HepG2细胞12、24、48、72h,各时相IP3含量显著低于对照组[（12.0±1.4）pmol/10^6cells、（7.5±0.8）pmol/10^6cells、（5.6±0.5）pmol/10^6 cells、（4.3±0.6）pmol/10^6 cellsvs（29.2±0.6）pmol/10^6 cells,P〈0.01];24h后Caspase3蛋白的RI显著高于对照组（2.7±0.2,7.4±0.5,7.4±0.5,30.7±1.6vs0.24±0.06,P〈0.05）;24h后各时相细胞凋亡率为显著高于对照组[（2.7±0.2）%、（7.4±0.5）%、（20.5±2.0）%、（30.7±1.6）%vs（2.6±0.1）%,P〈0.01]。结论Genistein能减少IP3生成,上调Caspase3蛋白表达,诱导肝癌细胞凋亡。     

Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia

The 2014 World Health Organization (WHO) classification of endometrial hyperplasia (EH) defines premalignant EH based on only cytologic atypia, disregarding architecture complexity. We aimed to assess the impact of architecture complexity on the risk of cancer in non‐atypical EH. A systematic review and meta‐analysis was performed by searching electronic databases form their inception to October 2018. All studies assessing the rates of progression to cancer in non‐atypical EH (simple vs complex) were included. Pooled relative risk (RR) for cancer progression was calculated; a p‐value < 0.05 was considered significant. Eight studies with 1066 women were included. The risk for progression of non‐atypical EH to cancer was significantly higher in complex EH than in simple EH (p < 0.0001), with an RR of 4.90. In conclusion, the complexity of glandular architecture significantly increases the risk of cancer in non‐atypical EH. Complex non‐atypical EH may be regarded as a low‐risk premalignant lesion rather than a benign condition.     

Fhit、p53表达与子宫内膜癌发生和发展的相关性

目的　探讨正常子宫内膜、子宫内膜增殖症及内膜癌组织中Fhit、p53蛋白表达,以及与子宫内膜癌发生、发展的关 系。方法　应用免疫组化S P法检测37例正常子宫内膜组织、27例单纯型增生过长、28例复杂型增生过长、38例子宫内膜癌 组织中Fhit、p53蛋白的表达。结果　在正常子宫内膜(增生期、分泌期)、子宫内膜增殖症(单纯型增生过长、复杂型增生过 长、不典型增生)、子宫内膜腺癌组织中Fhit蛋白的阳性表达率依次递增,差异有显著性(χ2=33.726,P<0.005)。p53蛋白的 阳性表达率也依次递增,差异有显著性(χ2=58.474,P<0.005)。在腺瘤型增生过长、不典型增生及子宫内膜腺癌组织中Fhit (χ2=6.571,P=0.037)、p53(χ2=6.915,P=0.032)蛋白的阳性表达率依次递增,差异有显著性。Fisher精确概率检验显示不 同肌层浸润组Fhit(P=0.033)、p53(P=0.034)蛋白的表达差异有统计学意义,而在年龄、是否绝经、手术病理分期、组织学分 级组的表达无统计学意义(P>0.05)。Spearman等级相关分析显示Fhit、p53蛋白表达呈正相关(r=0.900,P<0.05)。在月 经期内膜的腺上皮细胞胞质中的Fhit蛋白阳性表达率为72.72%。结论　Fhit、p53蛋白的表达与子宫内膜癌的发生相关。 Fhit基因可能成为子宫内膜组织早期癌变的分子标记物。     

脑血管病脑脊液神经降压素含量的改变

本研究测定21例正常对照组和68例脑血管病的脑脊液神经降压索含量。结果表明:(1)出血性脑血管病脑脊液神经降压素含量,比正常对照组显著增加;(2)缺血性脑血管病脑脊液神经降压素含量,比正常对照组显著减少。这提示,两类不同脑血管病脑脊液神经降压素含量,呈现明显的反向改变。     

Liquid-based endometrial cytology in the management of sonographically thickened endometrium

Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures.     

Complex papillary hyperplasia of the endometrium: An uncommon case report with cytopathological features and diagnostic implications

Papillary proliferations of the endometrium, without atypia have been uncommonly documented, including on cytology specimens. Herein, we present an uncommon case of a 55‐year‐old obese lady, on antihypertensive medications, who presented with history of irregular perimenopausal bleeding. A year ago, she was diagnosed with simple cystic hyperplasia on dilation and curettage specimen. Presently, she underwent endometrial aspiration. Cytology smears were prepared from the collected tissue specimen that was further submitted for histopathological analysis. Although the smears were initially diagnosed as negative for malignancy, the tissue sections were reported as a uterine papillary serous carcinoma (UPSC). Review of the smears revealed prominent overlapping clusters and papillary arrangements of relatively banal endometrial cells exhibiting focal metaplasia. Histopathology sections confirmed diagnosis of complex papillary hyperplasia (CPH). Immunohistochemical (IHC) stains reinforced this impression with diffuse estrogen receptor positivity, low Ki‐67/MIB1, and lack of diffuse p53 immunostaining. Subsequent hysterectomy, at the time of intraoperative consultation showed a small residual focus of CPH, restricted to endometrium with intramural leiomyomas and adenomyosis. This case is presented to highlight the fact that despite lack of significant atypia, cytological features like overlapping, clustering, and papillary formations are indicators of papillary lesions of the endometrium, including CPH, especially in postmenopausal women. On histopathology, in spite of conspicuous papillary formations, lack of significant nuclear pleomorphism, and tumor invasion are helpful features in avoiding an overdiagnosis of UPSC in such cases. IHC stains are supportive. Correct identification has significant therapeutic implications. Diagn. Cytopathol. 2015;43:163–168. © 2014 Wiley Periodicals, Inc.     

组织液压波在大白鼠胃经皮下组织传送规律的研究

注射０．９％的生理盐水到麻醉的大白鼠胃经的皮下，形成一个水泡，然后给予一个机械压力，由此产生一个组织液压波，测量组织液压在胃经上和胃经外的变化，发现了五种基本的组织液型及亚型，这些波型基于组织不同的粘弹性特性，组织液压波在经线上与经线外幅度差异与距离的线性回归方程为Ｙ＝－０．３５Ｘ＋１．９６，具有统计学显著性（Ｐ＜０．０１）。表明经脉线组织可能具有较好的渗透性和柔性。     

脑脊液病原菌变迁和耐药性分析

目的了解临床脑脊液培养阳性患者病原菌分布及其耐药情况。方法对2002—2008年临床脑脊液培养病原菌阳性患者标本进行回顾性统计分析;按常规方法进行细菌分离和鉴定;细菌药物敏感试验采用Kirby—Bauer纸片扩散法。结果分离出细菌97株,其中革兰阳性球菌占54．63％,革兰阴性菌占28．87％：新型隐球菌占13．40％。最常见的6种感染菌分别为凝固酶阴性葡萄球菌（40．21％）、不动杆菌属（8．25％）、铜绿假单胞菌（6．19％）、金黄色葡萄球菌（5．15％）、肺炎克雷伯菌（5．15％）、肠球菌属（5．15％）;耐甲氧西林凝固酶阴性葡萄球菌（MRSCN）和耐甲氧西林金黄色葡萄球菌（MRSA）的检出率分别是89．7％和80．0％。细菌对常用抗生素耐药性较高,未见万古霉素耐药的葡萄球菌;美洛培南以及头孢哌N／舒巴坦对革兰氏阴性杆菌有良好的抗菌活性。结论近6年来细菌性脑膜炎患者病原菌以革兰阳性球菌为主,主要为医院获得性细菌性脑膜炎感染。检出病原菌对常用抗生素耐药性较高,临床需警惕新型隐球菌的高发病趋势。