三维能量多普勒超声联合血清HE4、TK1、YKL-40对绝经后出血患者子宫内膜癌的预测价值

摘要 目的：研究三维能量多普勒超声联合血清人附睾蛋白4（HE4）、胸苷激酶1（TK1）、甲壳质酶蛋白40（YKL-40）对绝经后出血患者子宫内膜癌的预测价值。方法：选择我院2019年10月～2022年10月收治的150例绝经后出血患者。将其按照病理检查结果的差异分为子宫内膜癌组31例与子宫内膜良性增生组119例。对所有患者均开展三维能量多普勒超声检查,并检测血清HE4、TK1、YKL-40水平。以受试者工作特征曲线（ROC）分析三维能量多普勒超声联合血清HE4、TK1、YKL-40水平预测绝经后出血患者子宫内膜癌的效能。结果：子宫内膜癌组血流指数（FI）、血管形成指数（VI）、血管形成-血流指数（VFI）以及由该三参数构建的综合指数I相较于子宫内膜良性增生组均更高（均P＜0.05）。子宫内膜癌组血清HE4、TK1、YKL-40水平相较于子宫内膜良性增生组均更高（均P＜0.05）。经ROC曲线分析发现：三维能量多普勒超声联合血清HE4、TK1、YKL-40水平预测绝经后出血患者子宫内膜癌的曲线下面积（AUC）、灵敏度、特异度以及约登指数均高于上述四项单独预测。结论：三维能量多普勒超声联合血清HE4、TK1、YKL-40水平预测绝经后出血患者子宫内膜癌的效能较佳。     

Comparison of CA 15-3 and CEA in diagnosis and monitoring of breast cancer

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (greater than 3 ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6% of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA15-3 level and tumor stage in breast cancer. CA15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)     

乳腺良性肿块与乳腺癌患者的超声弹性成像对比

目的:对比乳腺良性肿块与乳腺癌患者的超声弹性成像,明确超声弹性成像的应用价值。方法:选取2014年5月-2016年1月我院乳腺肿块患者128人次共146例肿块,根据病理结果分为乳腺良性肿块和乳腺癌,比较超声弹性成像与病理结果。结果:128个患者共计肿块146例,99例结节为良性肿块,其中32例为乳腺纤维腺瘤,29例为乳腺增生结节,20例为乳腺脂肪瘤,6例为乳腺血管脂肪瘤,4例为乳腺导管腺瘤,8例为乳腺导管内乳头状瘤;47例肿块为恶性,其中37例肿块为浸润性导管癌,9例肿块为粘液腺癌,1例肿块为硬癌。乳腺良性肿块患者81人次共99例,其中1分43例(43.43%),2分34例(34.34%),3分18例(18.18%),4分4例(4.04%);乳腺癌患者47例,其中3分9例(19.15%),4分20例(42.55%),5分18例(38.30%)。超声弹性成像鉴别乳腺良性肿块与乳腺癌的灵敏度为95.96%,特异性为80.85%,准确度为91.10%,阴性预测值为90.48%,阳性预测值为91.35%。结论:超声弹性成像鉴别乳腺良性肿块与乳腺癌的灵敏度高达95.96%,具有较高准确度,可辅助诊断乳腺疾病。     

Fine needle aspiration biopsy of the breast. Value of nuclear morphometry after different sampling methods

OBJECTIVE: To study the potential of nuclear morphometry in supporting the interpretation of fine needle aspiration biopsy (FNAB) samples of the breast fixed in 50% ethanol and centrifuged on slides. STUDY DESIGN: Computerized morphometry was used to outline the nuclei of breast epithelial cells in breast cancer, fibroadenoma and fibrocystic disease. The diagnoses were histologically confirmed. We applied 2 different sampling methods (measurements done on cell groups and on free cells). RESULTS: The mean nuclear area of cell groups of malignant samples (23) varied from 42 to 125 microns 2, in fibroadenomas from 30 to 50 microns 2 and in fibrocystic disease from 26 to 57 microns 2. The mean nuclear area of free cells varied as follows: cancer, 66-181 microns 2; fibroadenoma, 33-70 microns 2; fibrocystic disease, 35-60 microns 2. Apocrine metaplasia was excluded from comparison on a morphologic basis. CONCLUSION: The study suggests that if the mean nuclear area of cell groups is < 42 microns 2, the lesion is probably benign; if > 57 microns 2, and apocrine metaplasia is excluded, malignancy should be considered. The differential diagnosis between carcinoma and fibroadenoma could be based on free cells: mean area of free cell nuclei < or = 65 microns 2 suggested a benign lesion, and of > or = 71 microns 2 suggested a malignant lesion. Morphometric nuclear size features (exemplified by nuclear area) appeared efficient in distinguishing between malignant and benign lesions when measured from free cells and cell groups.     

乳腺癌及癌前病变血管生成相关分子的表达及意义

目的探讨血管生成异常与乳腺癌发生发展的关系。方法采用免疫组化方法检测30例正常乳腺,30例普通性增生,30例非典型增生（AH）,20例导管内癌,50例浸润性导管癌组织中微血管密度（MVD）、VEGF及受体Flk-1/KDR的表达变化。结果各组CD34、VEGF及Flk-1/KDR的表达程度不同,浸润性导管癌组最高。随病程演进,MVD增加（P〈0.05）,VEGF及其受体Flk-1/KDR在血管内皮细胞表达渐进增高（P〈0.05）,但在病程初期各主要指标改变不明显,显著变化始于AH阶段。MVD在AH与导管内癌组间差异不显著（P〉0.05）,VEGF及Flk-1/KDR的表达在AH与导管内癌组间有显著差异（P〈0.05）。结论血管生成在乳腺癌发生发展过程中起着重要作用,血管生成异常可能是乳腺癌发生过程中的早期事件。VEGF及其受体Flk-1/KDR的表达异常可能是乳腺普通性增生-AH-乳腺癌这一癌性转化过程中血管生成异常的主要始动因素,VEGF及其受体Flk-1/KDR可能成为乳腺癌早期诊断及治疗的分子靶标。     

Transforming growth factor beta 1 serum levels in patients with preinvasive and invasive lesions of the breast

Transforming growth factor beta (TGF-beta)1 is thought to be involved in breast carcinogenesis. TGF-beta1 acts in an antiproliferative manner in the early stages of breast carcinogenesis, but promotes tumor progression and metastases in the advanced stages of the disease. No data have been published on serum TGF-beta1 in breast cancer. We investigated TGF-beta1 serum levels in patients with breast cancer (n=135), ductal carcinoma in situ (DCIS) I to III (n=67) or fibroadenoma (n=35), and in healthy women (n=40) to determine its value as a differentiation marker between malignant, pre-invasive and benign diseases and as a predictive marker for metastatic spread. Median (range) TGF-beta1 serum levels in patients with breast cancer, DCIS I-III or benign breast lesions and in healthy women were 48.8 (18-82.4) pg/mL, 45.3 (26.9-58.3) pg/mL, 47.2 (17.2-80.5) pg/mL and 51.6 (30.9-65.1) pg/mL, respectively (p=0.2). In breast cancer patients TGF-beta1 serum levels showed no statistically significant correlation with tumor stage, lymph node involvement, histological grade, estrogen receptor status and progesterone receptor status. Our data fail to indicate any correlation between serum TGF-beta1 levels and clinicopathological parameters of breast diseases. Serum TGF-beta1 levels do not provide clinical information in addition to established tumor markers.     

Analysis of the microvasculature and tissue type ratios in normal vs. benign and malignant breast tissue

OBJECTIVE: To analyze the microvasculature and tissue type ratios in normal vs. benign and malignant breast tissue to establish a baseline for expected values against which future imaging studies can be benchmarked. STUDY DESIGN: Using computer-assisted techniques on immunostained breast tissue (normal [n = 28], fibrocystic [n = 37], fibroadenomas [n = 19], invasive carcinomas [n = 19]), values were obtained for microvessel density (MVD), mean vessel area (MVA), vessel orientation (shape) and epithelial:stromal ratio (E:S). Measurement reproducibility and the effects of fibroadenoma stromal hyalinization and fibrocystic disease severity were also tested. RESULTS: Value ranges for the 4 diagnostic groups were significantly different (P < .001). For invasive breast carcinomas, E:S and MVD were significantly higher (P < .001) but MVA was smaller as compared to that in fibroadenomas. Peripherally vs. centrally there was no significant difference in MVD, MVA or vessel shape in the neoplasms. Decreases in E:S and MVD correlated with fibroadenoma stromal hyalinization. Increases in E:S and MVA correlated with more severe fibrocystic disease. Correlation coefficients for measurement reproducibility were high across the diagnostic categories. CONCLUSION: This study established a specific, reproducible, computer-assisted technique and baseline of expected values for morphologic criteria in normal, benign and malignant breast tissue that may be used in the future to correlate new breast imaging responses with these underlying biologic properties.     

Fine needle aspiration of breast lesions in women aged 30 and under

Fine needle aspiration (FNA) biopsies of 1,598 breast masses were performed between 1983 and 1989, and of them, 48 were from women aged 30 and under for whom a cytologic diagnosis was made by FNA and histologic follow-up was available. In 37 (77%) of the cases, both the cytologic and histologic diagnoses were benign. Fibroadenoma (20/37) and fibrocystic changes (14/37) were the most common benign lesions aspirated. Eight (17%) FNAs showed cytologic atypia. Four of these atypical lesions proved to be benign (two fibroadenomas, two fibrocystic changes). Epithelial proliferation in fibroadenomas and fibrocystic changes and cellular stroma in a fibroadenoma mimicking phylloides tumor were the causes of atypia in these biopsies. Four of the eight atypical lesions were shown to be carcinoma at biopsy (three infiltrating duct, one atypical medullary). Low cellularity, epithelial cohesiveness mimicking a fibroadenoma and background lactational changes in a pregnant patient were the causes of the atypical, rather than unequivocally malignant, diagnoses in these cases. In three patients (6%), a diagnosis of carcinoma was made by FNA and confirmed histologically (all were infiltrating duct carcinoma). Although most breast masses in women aged 30 and under are benign, cytologic atypia in a breast fine needle aspirate in this age group warrants a surgical biopsy. Clinical follow-up alone may be appropriate for young women with clinically nonsuspicious breast masses without cytologic atypia.     

An autocrine VEGF/VEGFR2 and p38 signaling loop confers resistance to 4-hydroxytamoxifen in MCF-7 breast cancer cells

Tamoxifen, a partial estrogen receptor antagonist, is part of the standard treatment of both primary and advanced breast cancers. However, significant proportions of breast cancers are either de novo resistant or develop tamoxifen resistance during the course of treatment through mechanisms which have been only partly characterized. We have previously found that high vascular endothelial growth factor (VEGF) or VEGF receptor 2 (VEGFR2) expression and concomitant high p38 mitogen-activated protein kinase activity within breast cancers predict a poor outcome for tamoxifen-treated patients. Here, we have molecularly dissected how VEGF/VEGFR2 and p38 are linked, and contribute to tamoxifen resistance within breast cancer using a MCF-7 BC cell model with different 4-hydroxytamoxifen (4-OHT) responsiveness. We report that MCF-7 breast cancer cell lines with tamoxifen resistance have increased secretion of VEGF and increased signaling through VEGFR2 compared with parental MCF-7 cells. 4-OHT treatment caused the ablation of VEGF secretion in parental MCF-7 cells, whereas in the tamoxifen-resistant subline, a VEGF/VEGFR2 signaling loop was still evident upon treatment. Increased basal levels of total and phosphorylated p38 were observed in tamoxifen-resistant cells. Pharmacologic inhibition of p38 reduced the proliferation of both tamoxifen-responsive and tamoxifen-resistant cells and showed an additive growth-inhibitory effect in combination with 4-OHT. A connection between VEGF/VEGFR2 and p38 signaling was identified by VEGF and VEGFR2 knockdown, which equally reduced both the total and the active forms of p38 in tamoxifen-resistant cells. Taken together, our results suggest that decreased sensitivity to 4-OHT is caused by a death-protecting VEGF/VEGFR2 and p38 growth factor loop in breast cancer cells. Inhibition of these signaling pathways may be beneficial to overcome tamoxifen resistance.     

Trace element content in breasts with fibrocystic disease

The trace elements antimony, bromine, cesium, cobalt, iron, rubidium, scandium, strontium and zinc were determined by instrumental neutron activation analysis in breast tissue samples with fibrocystic disease and in samples with fibroadenoma tumors. The histological lesions of each breast sample with fibrocystic disease were recorded, and a statistical analysis of the lesions in combination with the determined trace elements was carried out. The results showed that the element mean values in fibroadenoma tumors are higher than those of fibrocystic disease. Some other remarkable results of statistical examination are also presented.     

Circulating CA 15.3 levels in breast cancer. Our present experience

CA 15.3 is an antigen expressed by human breast carcinoma cells, and defined by two monoclonal antibodies, 115D8 and DF3. We used IRMA to determine the circulating serum levels of CA 15.3 in 1178 subjects with breast cancer, non-breast malignancies, benign diseases and controls. A threshold level of 40 U/ml was established with 140 healthy controls and 650 patients with benign diseases (respectively 0% subjects and 1.5% patients had abnormal antigen levels). Elevated CA 15.3 was found in 12 of 184 patients with malignancies different from breast cancer (6.5%), either epithelial carcinomas with distant metastases, mainly in the liver, or primary liver tumors. Breast cancer patients (n = 204) were analysed by prior therapy, UICC stage and WHO response to therapy. Eight of 134 (5.9%) patients with stage II or III breast cancer at presentation and no evidence of disease (NED) had elevated CA 15.3. All of 22 patients with stage IV breast cancer not responding to therapy (SD and PD) had antigen levels greater than 40 U/ml, as did 10 of 34 (29.4%) stage IV patients in objective response (CR + PR). Three of 14 pretreatment patients had abnormal marker levels, and they later proved to have distant metastases. Serum CA 15.3 values were statistically different (p less than 0.01) in NED (20.6 +/- 11.2 U/ml), CR + PR (33.5 +/- 24.0 U/ml), stable disease (98.8 +/- 50.4 U/ml) and progressive disease (greater than 200 U/ml) breast cancer patients. Our results suggest that circulating CA 15.3 antigen levels agree with the stage of breast cancer and with the response to therapy.     

Lipid peroxidation and antioxidant status in blood and tissue of malignant breast tumor and benign breast disease

Changes in the levels of malondialdehyde (MDA), nitrate and nitrite (as an index of nitric oxide production), lipid hydroperoxide (LOH), total antioxidant capacity (TAC), lipids (total cholesterol and triglycerides) and lipoproteins (HDL- and LDL-cholesterol) were estimated in breast cancer patients (n = 15) and benign breast disease (n = 15). Serum and tissue MDA levels were found to be decreased in breast cancer patients compared to the benign group (p < 0.05). In contrast, nitrate and nitrite levels were increased in serum and tissue of the cancer group compared to benign breast disease patients (p < 0.05). Compared to the benign group, tissue TAC levels were elevated in the breast cancer patient group (p < 0.05). Total cholesterol and HDL-cholesterol were elevated in the benign group compared with cancer patients (p < 0.05). These findings support the hypothesis that lipid peroxidation in serum and tissue of benign breast disease is greater than in breast cancer. However, the enhanced levels of nitric oxide may be in response to inflammation in patients with breast cancer. Total antioxidant status is lower in benign tissue than in cancerous tissue, probably to compensate for this elevated free radical production.     

肿块型乳腺癌的超声造影特征及定量参数与sE-cad、sTNFR-P55的相关性及其诊断价值分析

摘要 目的：探讨肿块型乳腺癌的超声造影（CEUS）特征及定量参数与可溶性E-钙黏蛋白（sE-cad）、可溶性肿瘤坏死因子受体P55（sTNFR-P55）相关性研究,并探讨其对肿块型乳腺癌的诊断价值。方法：选取2019年1月至2021年1月于本院诊治并行CEUS检查的162例乳腺肿块患者,根据病理结果分为肿块型乳腺癌组（82例）和良性组（80例）,另选取本院体检健康的80例女性作为对照组。三组均行血清sE-cad、sTNFR-P55水平检测。比较肿块型乳腺癌组与良性组CEUS特征及定量参数的差异,采用Pearson相关分析肿块型乳腺癌患者CEUS定量参数与血清sE-cad、sTNFR-P55水平的相关性。对CEUS、血清sE-cad、sTNFR-P55水平单独或三者联合诊断的方式采用敏感度、特异度、准确性、阳性预测值、阴性预测值指标表达。结果：肿块型乳腺癌组大部分表现为增强后形态不规则、高增强、向心性灌注、造影剂分布不均匀以及呈慢出型的强化方式,且所占比例显著高于良性组（P<0.05）。与良性组相比,肿块型乳腺癌组CEUS定量参数TTP、G显著降低（P<0.05）,而PI、K显著升高（P<0.05）。肿块型乳腺癌组血清sE-cad、sTNFR-P55水平显著高于良性组、对照组（P<0.05）,且良性组血清sE-cad、sTNFR-P55水平还显著高于对照组（P<0.05）。肿块型乳腺癌患者的CEUS定量参数TTP、G与血清sE-cad、sTNFR-P55水平呈负相关（P<0.05）;而PI、k与血清sE-cad、sTNFR-P55水平呈正相关（P<0.05）。CEUS联合血清sE-cad、sTNFR-P55水平诊断肿块型乳腺癌的准确度、敏感度、特异度、阳性预测值、阴性预测值最高。结论：CEUS特征及定量参数对肿块型乳腺癌具有一定的鉴别诊断价值,而且CEUS定量参数与血清sE-cad、sTNFR-P55水平具有一定的相关性,说明CEUS定量参数可在一定程度上可反映乳腺癌的恶性生物学行为;同时CEUS联合血清sE-cad、sTNFR-P55水平检测有助于提高对肿块型乳腺癌的鉴别诊断价值,进一步为临床医生的定性判断提供更加科学的影像学依据。     

血清HE4、VEGF、MCP-1及CCL20与乳腺癌患者保乳术后局部复发的关系研究

摘要 目的：探讨血清人附睾蛋白4（HE4）、血管内皮生长因子（VEGF）、单核细胞趋化因子-1（MCP-1）及CC趋化因子配体20（CCL20）与乳腺癌患者保乳术后局部复发的关系。方法：选择2015年7月~2018年7月期间本院收治的乳腺癌患者312例作为研究对象,均符合保乳术手术指征,成功实施乳腺癌保乳术,所有患者均随访3年。检测两组血清HE4、VEGF、MCP-1、CCL20水平情况,单因素及多因素Logistic回归分析影响术后局部复发的因素。使用受试者工作特征（ROC）曲线分析HE4、VEGF、MCP-1、CCL20水平单独及联合检测对保乳术后局部复发的预测价值。结果：随访过程中失访6例,剩余的306例患者根据随访结果,分为局部复发组27例、无局部复发组279例,局部复发率为8.82%。局部复发组的血清HE4、VEGF、MCP-1、CCL20水平均高于无局部复发组（P<0.05）。单因素分析结果显示,乳腺癌患者保乳术后局部复发与年龄、淋巴结转移、切缘状态、人表皮生长因子受体2（Her-2）、细胞增殖相关抗原（Ki-67）、术后规范化疗、术后足程放疗有关（P<0.05）。多因素Logistic回归分析结果显示术后规范化疗、年龄偏高、术后足程放疗是保乳术后局部复发的保护因素,HE4、VEGF、MCP-1、CCL20水平偏高,切缘状态、Her-2、Ki-67阳性以及淋巴结转移是保乳术后局部复发的危险因素（P<0.05）。HE4、VEGF、MCP-1、CCL20联合应用预测乳腺癌患者保乳术后局部复发的效能高于单一指标应用。结论：乳腺癌保乳术后局部复发患者体内HE4、VEGF、MCP-1、CCL20水平高表达,四指标联合检测可辅助预测保乳术后局部复发。且乳腺癌患者保乳术后复发还受到切缘状态、Her-2、Ki-67等多种因素的影响。     

Guidelines on chemotherapy in advanced stage gynecological malignancies: an evaluation of 224 professional societies and organizations

Background

Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence.

Methods

We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed.

Results

Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy.

Conclusions

Clinical practice guidelines are provided by the minority of professional societies and organizations. Available guidelines tend to recommend chemotherapy even for diseases where the effect of chemotherapy is controversial and recommendations are based on scant evidence.     

Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation

Impaired Ag-presenting function in dendritic cells (DCs) due to abnormal differentiation is an important mechanism of tumor escape from immune control. A major role for vascular endothelial growth factor (VEGF) and its receptors, VEGFR1/Flt-1 and VEGFR2/KDR/Flk-1, has been documented in hemopoietic development. To study the roles of each of these receptors in DC differentiation, we used an in vitro system of myeloid DC differentiation from murine embryonic stem cells. Exposure of wild-type, VEGFR1(-/-), or VEGFR2(-/-) embryonic stem cells to exogenous VEGF or the VEGFR1-specific ligand, placental growth factor, revealed distinct roles of VEGF receptors. VEGFR1 is the primary mediator of the VEGF inhibition of DC maturation, whereas VEGFR2 tyrosine kinase signaling is essential for early hemopoietic differentiation, but only marginally affects final DC maturation. SU5416, a VEGF receptor tyrosine kinase inhibitor, only partially rescued the mature DC phenotype in the presence of VEGF, suggesting the involvement of both tyrosine kinase-dependent and independent inhibitory mechanisms. VEGFR1 signaling was sufficient for blocking NF-kappaB activation in bone marrow hemopoietic progenitor cells. VEGF and placental growth factor affect the early stages of myeloid/DC differentiation. The data suggest that therapeutic strategies attempting to reverse the immunosuppressive effects of VEGF in cancer patients might be more effective if they specifically targeted VEGFR1.     

Quantitative cytological assessment of Ki67 and AgNORs using computer-digitized image analysis of four clinicopathological breast lesions

Analysis of silver-stained proteins associated with nucleolar organiser regions (AgNORs) is proposed as a marker of cellular proliferation. This study describes the application of AgNORs and Ki67 in breast lesions. Sixty-one cases including fibroadenoma (FA), fibrocystic disease (FCD), ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) were studied by image analysis to evaluate quantitative changes in AgNORs in both Ki67-positive, and Ki67-negative smears. The Ki67 index was assessed. Morphometric features of cell nuclei and AgNORs were determined by digitized computer image analysis (Prodit 5.2). The growth fraction was 5.08 for FA, 5.71 for FCD, 16.75 for DCIS and 23.26 for IC. The mean nuclear area was significantly higher in malignant cells than those of fibroadenoma and fibrocystic disease. In Ki67-positive cells the total area, long axis and number of AgNORs increased progressively across disease groups. Eccentricity of AgNORs and AgNORs: nuclear area ratios were significantly increased in malignant breast lesion in comparison with benign lesion in Ki67 positive cells. In Ki67 negative cells, the highest value of AgNORs was observed in DCIS. The AgNORs: nuclear area ratio demonstrated a statistically significant trend across the disease groups. This study demonstrates that the growth fraction, mean nuclear area and selected AgNORs features have potential for differentiating benign from malignant breast tumours.     

超声造影联合HE4、CA125、CA153在子宫内膜癌诊断中的价值研究

摘要 目的：为提高对子宫内膜癌的早期诊断,本研究对超声造影联合肿瘤标志物人附睾蛋白4（human epididymis protein-4,HE4）血清糖类抗原125（carbohydrate antigen 125,CA125）及153（CA153）在子宫内膜癌中的诊断价值进行研究。方法：以80例疑似子宫内膜癌患者为研究组,另以80例于本院体检的健康女性为对照组。对患者进行超声造影检查,比较两组血清HE4、CA125以及CA153水平,考察超声造影联合HE4、CA125及CA153对子宫内膜癌的诊断作用。结果：本研究中80例疑似患者中,子宫内膜癌患者有49例,子宫内膜良性病变患者31例,而超声造影检查显示子宫内膜癌患者有41例,良性病变39例,与金标准检查结果有一定的差异,单纯的超声造影检查对子宫内膜癌的诊断有局限性。子宫内膜癌和良性病变患者的病变区灌注的时间、增强强度以及增强均度都有显著差异（P<0.05）。对照组血清HE4、CA125及CA153水平分别为82.31±15.45 pmol/mL、22.31±6.21 U/mL、16.45±4.91 U/mL,研究组血清HE4、CA125及CA153水平分别为159.28±24.01 pmol/mL、42.88±5.73 U/mL、28.30±3.76 U/mL,经统计,研究组各项指标均显著高于对照组（P<0.05）。超声造影的灵敏度为79.3 %、特异度为67.34 %、阳性似然比为2.54、阴性似然比为0.25、阳性预测值为84.63 %、阴性预测值为60.51 %及符合率为72.19 %;联合检测的灵敏度为86.58 %、特异度为78.92 %、阳性似然比为3.11、阴性似然比为0.23、阳性预测值为93.19 %、阴性预测值为67.42 %及符合率为77.90 %。结论：超声造影联合HE4、CA125及CA153检测对子宫内膜癌诊断价值更高,HE4、CA125及CA153能辅助提高超声造影的诊断效果。     

坤泰胶囊联合米非司酮治疗围绝经期功能失调性子宫出血的疗效及对bFGF、VEGF水平的影响

摘要 目的：分析坤泰胶囊联合米非司酮治疗围绝经期功能失调性子宫出血（DUB）的疗效及对碱性成纤维细胞生长因子（bFGF）、血管内皮细胞生长因子（VEGF）水平的影响。方法：选取2021年10月-2022年10月在合肥市第一人民医院滨湖院区妇科门诊就医的88例围绝经期DUB患者作为研究对象,采用随机数据表法将其分为研究组和对照组,每组各44例,两组患者入组后均给予常规对症治疗,对照组患者在此基础上给予口服米非司酮胶囊,用量为每日1次,每次10 mg。研究组患者在对照组疗法的基础上给予口服坤泰胶囊,用量为每日3次,每次2 g。两组患者均连续服用3个月。对两组患者的疗效指标及治疗前和治疗3个月时的子宫内膜厚度、血清卵泡刺激素（FSH）、黄体生成素（LH）、泌乳素（PRL）、雌二醇（E₂）、bFGF、VEGF水平进行比较。对两组患者治疗期间的不良反应进行比较。结果：研究组患者的疗效等级分布优于对照组,有效率高于对照组（P<0.05）。两组患者治疗前的子宫内膜厚度及血清性激素、bFGF、VEGF水平的差异均无统计学意义（P>0.05）,在治疗3个月末,两组患者的子宫内膜厚度及血清FSH、LH、PRL、E₂水平均较治疗前降低,血清bFGF、VEGF水平均较治疗前升高（P<0.05）,研究组患者在治疗3个月末的子宫内膜厚度及血清FSH、LH、PRL、E₂水平均低于对照组,血清bFGF、VEGF水平均高于对照组（P<0.05）。两组不良反应均为轻度,在未经治疗的情况下患者可耐受,未见因不良反应而中断治疗的患者。两组各项不良反应发生率和不良反应总发生率的差异均无统计学意义（P>0.05）。结论：在围绝经期DUB的治疗中,采用坤泰胶囊联合米非司酮的中西医治疗方案,在临床疗效优于单用米非司酮方案,能够更加显著地改善血清激素水平、抑制子宫内膜增生、提升bFGF、VEGF等血管生成因子的表达水平。     

The Decrease of Mineralcorticoid Receptor Drives Angiogenic Pathways in Colorectal Cancer

Angiogenesis plays a crucial role in tumor growth and progression. Low expression of mineralocorticoid receptor (MR) in several malignant tumors correlates with disease recurrence and overall survival. Previous studies have shown that MR expression is decreased in colorectal cancer (CRC). Here we hypothesize that decreased MR expression can contribute to angiogenesis and poor patient survival in colorectal malignancies. In a cohort of CRC patients, we analyzed tumor MR expression, its correlation with tumor microvascular density and its impact on survival. Subsequently, we interrogated the role of MR in angiogenesis in an in vitro model, based on the colon cancer cell line HCT116, ingenierized to re-express a physiologically controlled MR. In CRC, decreased MR expression was associated with increased microvascular density and poor patient survival. In pchMR transfected HCT116, aldosterone or natural serum steroids largely inhibited mRNA expression levels of both VEGFA and its receptor 2/KDR. In CRC, MR activation may significantly decrease angiogenesis by directly inhibiting dysregulated VEGFA and hypoxia-induced VEGFA mRNA expression. In addition, MR activation attenuates the expression of the VEGF receptor 2/KDR, possibly dampening the activation of a VEGFA/KDR dependent signaling pathway important for the survival of tumor cells under hypoxic conditions.