乳腺癌血行转移与血管生成相关因子相关性研究

目的探讨血管生成相关因子:癌基因HER2、缺氧诱导因子(HIF)和血管内皮细胞生长因子(VEGF)在乳腺癌组织中的表达及其与血行转移的相关性。方法应用免疫组织化学技术(SP法)检测51例乳腺浸润性导管癌组织中HER2、HIF-1α、VEGF蛋白的表达并随访其术后5年内远处血行转移的情况。结果51例乳腺浸润性导管癌组织中HER2、HIF-1a和VEGF表达均彼此相关。单因素分析显示44例乳腺浸润性导管癌中HER2、VEGF、淋巴结转移和临床肿瘤分期与癌的远处血行转移相关,HIF-1α表达与远处血行转移不相关(P>0.05)。23例淋巴结阴性乳腺癌中,仅VEGF表达与其远处血行转移密切相关(P<0.05)。结论乳腺浸润性导管癌组织中HER2可能通过HIF-1α途径调节VEGF蛋白的表达,参与乳腺癌血管的生成。VEGF表达可作为术后预测血行转移的指标之一,HER2过度表达和HIF-1α表达不能预测远处血行转移。     

新疆维吾尔自治区维吾尔族和哈萨克族及汉族女性胆囊结石的流行病学调查

背景　新疆维吾尔自治区胆囊结石患病率较高,我国女性胆囊结石患病率高于男性,但目前缺乏关于新疆维吾尔自治区女性胆囊结石患病率的研究。目的　了解新疆维吾尔自治区维吾尔族、哈萨克族、汉族女性胆囊结石患病率及其影响因素,为其胆囊结石预防及治疗提供依据。方法　2011年6—9月采用典型抽样再多阶段分层随机抽样的方法选取新疆维吾尔自治区女性居民为调查对象,采用统一自制且翻译成维吾尔文的调查问卷对其进行基本情况调查,同时对调查对象行肝脏和胆囊腹部超声检查。比较不同民族以及各民族不同初潮年龄、月经不调、生育数量、分娩年龄女性胆囊结石患病率,并采用多因素Logistic回归分析女性胆囊结石患病率的影响因素。结果　共发放问卷3 508份,有效问卷3 175份,有效回收率为90.5%。3 175例女性胆囊结石患病率为16.9%（535/3 175）,其中维吾尔族、哈萨克族、汉族女性胆囊结石患病率分别为24.0%（222/924）、10.8%（94/873）、15.9%（219/1 378）。3个民族间胆囊结石患病率比较,差异有统计学意义（χ2=57.913,P<0.001）。多因素Logistic回归分析结果显示,初潮年龄〔OR=1.167,95%CI（1.007,1.353）〕、月经不调〔OR=6.486,95%CI（4.636,9.532）〕、生育数量〔OR=1.355,95%CI（1.237,1.483）〕是维吾尔族女性胆囊结石的影响因素（P<0.05）;初潮年龄〔OR=1.296,95%CI（1.007,1.668）〕、生育数量〔OR=1.240,95%CI（1.022,1.504）〕是哈萨克族女性胆囊结石的影响因素（P<0.05）;生育数量〔OR=1.341,95%CI（1.214,1.482）〕、分娩年龄〔OR=0.942,95%CI（0.892,0.996）〕是汉族女性胆囊结石的影响因素（P<0.05）。结论　新疆维吾尔自治区女性胆囊结石患病率较高,其中维吾尔族女性胆囊结石患病率与初潮年龄、月经不调、生育数量有关;哈萨克族女性胆囊结石患病率主要与初潮年龄、生育数量有关;汉族女性胆囊结石患病率主要与生育数量、分娩年龄有关。因此临床工作中应重点关注初潮年龄延迟,生育数量多,分娩年龄小的女性,尤其是胆囊结石患病率较高的维吾尔族人群。     

A randomized Phase III trial of neoadjuvant recombinant human endostatin,docetaxel and epirubicin as first‐line therapy for patients with breast cancer (CBCRT01)

To further assess the efficacy and safety of recombinant human endostatin (rh‐endostatin), a Phase III, multicenter, prospective, randomized, controlled clinical trial was conducted. Patients to be treated with neoadjuvant docetaxel and epirubicin (DE) or DE plus rh‐endostatin (DEE) were eligible for this trial. The primary endpoint was clinical/pathological response. Secondary endpoints included adverse events and quality of life (QOL). Finally, 803 patients were enrolled and randomly assigned to receive DE (n = 402) or DEE (n = 401) regimen. After three cycles of neoadjuvant therapy, “complete response” achieved in 14.2% of patients in DEE group versus 6.7% in DE group, “partial response” achieved in 76.8% versus 71.1%, while “stable disease” in 6.0% versus 18.9%, “progressive disease” in 3.0% versus 3.2% of patients. The rate of objective response in DEE and DE group was 91.0% and 77.9%, respectively (p < 0.001). In spite of a relatively higher pathological complete response achieved following the combination therapy, no significant difference was found between two arms. Adverse events were mostly of Grades 1–2. No significant difference in adverse event and QOL was found between the two arms. In conclusion, the combination of chemotherapy and rh‐endostatin achieved better outcomes than chemotherapy alone, and thus can be considered as a promising therapeutic strategy for breast cancer.     

激素受体/人表皮生长因子受体2阳性乳腺癌治疗研究进展

乳腺癌是我国女性最常见的恶性肿瘤,根据雌激素受体（ER）和孕激素受体（PR）的表达以及人表皮生长因子受体2（HER2）基因的扩增状态,乳腺癌被分为多个分子亚型。不同的亚型预后也不同,其中HER2阳性（+）乳腺癌与HER2阴性（-）乳腺癌相比,更具侵袭性,且预后更差。激素受体（HR）+/HER2+乳腺癌由于在HR与HER2信号通路之间存在交互转导通路,以致内分泌治疗及抗HER2治疗相互影响、制约。如何合理而有效地治疗HR+/HER2+乳腺癌成为乳腺癌治疗的难点之一。本文简述了HR+/HER2+乳腺癌的治疗现状以及在抗HER2治疗、内分泌治疗、免疫治疗、磷脂酰肌醇3-激酶（PI3K）/雷帕霉素靶蛋白（mTOR）通路抑制剂等方面的探索之路。     

乳管冲洗术治疗急性化脓性乳腺炎的临床观察

目的：观察乳管冲洗术与单纯应用抗生素治疗急性化脓性乳腺炎的疗效。方法：共观察68例急性化脓性乳腺炎患者,随机分为两组,对照组34例,单纯应用抗生素治疗;治疗组34例,采用乳管冲洗术联合全身应用抗生素治疗。结果：治疗组患者均痊愈,治愈时间缩短,无创伤,无痛苦,消费低;对照组有1例形成脓肿,平均治愈时间延长,治疗组优于对照组（P〈0.05）。结论：乳管冲洗术治疗急性化脓性乳腺炎有较好疗效,应用较安全。     

高血压与肠道菌群相关性研究文献计量学分析

目的　分析评价2008—2017年SCI收录的高血压与肠道菌群相关性研究的文献情况,为进一步开展该领域的研究提供参考。方法　以Web of Science核心合集数据库为资料来源,选用Web of Science核心合集数据库中的高级检索,分别对高血压（hypertension）和肠道菌群（gut microbiota）的同义词、上下位类主题词采用布尔运算符“OR”组配,组间采用“AND”组配,字段标识符选择主题（TS）;检索年限：2008—2017年;检索日期：2017-11-01;对高血压与肠道菌群相关性研究文献资料进行描述性统计分析。结果　共纳入62篇文献。发文量从2015年开始逐年增多;Current Hypertension Reports发文最多（5篇）;Circulation的影响因子最高（19.309）;高被引文献（被引量≥9.02）有14篇;文献合作度7.29,文献合作率91.94%;发文量≥2篇的作者主要来自美国;有科研基金资助的文献48篇（77.42%）;本研究共涉及88个关键词,研究方向以心血管系统与心脏病学为主,研究内容主要集中于肠道菌群失调与高血压的相关性。结论　高血压与肠道菌群的相关性研究目前尚处于起步阶段,存在发文期刊分散、学术影响力小等不足,需对二者的因果关系、作用机制等关键问题继续探索、验证,在研究内容和研究质量上不断丰富和优化。     

Long Noncoding RNA FOXC2-AS1 Predicts Poor Survival in Breast Cancer Patients and Promotes Cell Proliferation

Breast cancer (BC) is the most common malignant tumor in women. Recently, long noncoding RNAs (lncRNAs) have been proposed as critical regulators in biological processes, including tumorigenesis. FOXC2-AS1, a single antisense oligonucleotide RNA transcribed from the negative strand of forkhead box protein C2 (FOXC2), has been identified as an oncogene in osteosarcoma. In the present study, we investigated the prognosis value and biological role of FOXC2-AS1 in BC. Our findings revealed that FOXC2-AS1 was significantly increased in BC tissues and cell lines, and Kaplan–Meier survival analysis indicated that a high level of FOXC2-AS1 was associated with poor prognosis of BC patients. Loss of function revealed that silenced FOXC2-AS1 significantly suppressed the proliferation ability, and flow cytometric analysis illustrated the influence of FOXC2- AS1 on cell cycle and apoptosis rate. Finally, we found that cyclin D1, cyclin D2, and cyclin D3 were all partly positively modulated by FOXC2-AS1 in BC. Collectively, FOXC2-AS1 may serve as a promising prognostic biomarker and therapeutic target for BC patients.     

Multicenter clinical study for evaluation of efficacy and safety of transdermal fentanyl matrix patch in treatment of moderate to severe cancer pain in 474 Chinese cancer patients

Objective: Although a new matrix formulation fentanyl has been used throughout the world for cancer pain management, few data about its efficacy and clinical outcomes associated with its use in Chinese patients have been obtained. This study aimed to assess the efficacy and safety of the new system in Chinese patients with moderate to severe cancer pain. Methods: A total of 474 patients with moderate to severe cancer pain were enrolled in this study and were treated with the new transdermal fentanyl matrix...     

Pyrotinib Sensitizes 5-Fluorouracil-Resistant HER2⁺ Breast Cancer Cells to 5-Fluorouracil

5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for breast cancer. However, acquired chemoresistance leads to a loss of its efficacy; methods to reverse are urgently needed. Some studies have shown that pyrotinib, an ErbB receptor tyrosine kinase inhibitor, is effective against HER2+ breast cancer. However, whether pyrotinib sensitizes 5-FU-resistant breast cancer cells to 5-FU is unknown. We hypothesized that the combination of pyrotinib and 5-FU would show synergistic antitumor activity, and pyrotinib could reverse 5-FU resistance in HER2+ breast cancer cells in vitro and in vivo. Our data showed that pyrotinib inhibited the growth of 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines. 5-FU remarkably suppressed the growth of SKBR-3 and MAD-MB-453 cells. However, SKBR-3/FU and MADMB-453/FU cells showed resistance to 5-FU. A combination of pyrotinib and 5-FU resulted in the synergistic inhibition of the growth of the 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines. Pyrotinib decreased significantly the IC50 values of 5-FU and the thymidylate synthase (TS) mRNA expression levels in the 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines and increased significantly the intracellular concentration of 5-FU in SKBR-3/FU and MDA-MB-453/FU cells. In addition, pyrotinib reduced the ABCG2 mRNA and protein expression levels in SKBR-3/FU and MDA-MB- 453/FU cells and downregulated the protein expression levels of pAKT, pHER2, and pHER4 in all four cell lines. After TS or ABCG2 in 5-FU-resistant breast cancer cells was knocked down, the sensitivity of SKBR-3/ FU and MDA-MB-453/FU cells to 5-FU was restored. Moreover, in vivo experiments demonstrated that pyrotinib in combination with 5-FU more effectively inhibited SKBR-3/FU tumor growth than either pyrotinib or 5-FU alone. In conclusion, our findings suggest that pyrotinib could restore sensitivity of 5-FU-resistant HER2+ breast cancer cells to 5-FU through downregulating the expression levels of TS and ABCG2.