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Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.  相似文献   
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Introduction

Left ventricular (LV) dysfunction is estimated to occur in 10%–25% of the general intensive care unit (ICU) population and is frequently seen as regional wall motion abnormalities (RWMAs). Although RWMA is mostly attributed to myocardial ischemia or infarction, some studies have suggested that nonischemic RWMA might also be prevalent. We sought to establish that RWMA can be seen in critically ill patients with normal coronary arteries and to explore reasons for RWMA in this population.

Methods

In this retrospective study, data from the hospital angiography register and the ICU register were collated between 2012 and 2019. Patients were identified who underwent angiography in conjunction with their ICU stay and had RWMA on echocardiography. Patients were divided into either those with non-obstructed or those with obstructed coronary arteries. Cardiac magnetic resonance imaging (cMRI) examinations were reviewed if they had been performed on patients with non-obstructed coronaries.

Results

We identified 53 patients with RWMA and non-obstructed coronary arteries and 204 patients with RWMA and obstructed coronary arteries. Patients with non-obstructed coronary arteries were more often female, younger, and had fewer cardiovascular risk factors. They less commonly had ST elevation, but more frequently had T-wave inversion or serious arrhythmias. Troponin levels were higher in patients with obstructed coronary arteries, but NT-proBNP was similar between the groups. There were no differences in risk-adjusted 90-day mortality between patients with non-obstructed versus obstructed coronary arteries (OR 1.21, [95% CI 0.56–2.64], p = .628). In those with non-obstructed coronary arteries, follow-up echocardiography was available for 38 patients, of whom 30 showed normalization of cardiac function. Of the 14 patients with non-obstructed coronary arteries on whom cMRI was performed, 7 had a tentative diagnosis of Takotsubo syndrome or myocardial stunning; 4 had a myocardial infarction (preexisting in 3 cases); 1 patient had acute myocarditis; 1 patient had post-myocarditis; and 1 patient was diagnosed with dilated cardiomyopathy.

Conclusion

RWMA can be seen to occur in critically ill patients in the absence of coronary artery obstruction. Several conditions can cause regional hypokinesia, and cMRI is useful to evaluate the underlying etiology.  相似文献   
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目的 对3例怀疑M蛋白相关性杆状体肌病患者进行肌肉病理检查、M蛋白筛查明确诊断,提高对这一罕见疾病的认识并探讨对此疾病的诊疗方案。 方法 报道3例M蛋白相关性杆状体肌病,结合文献复习对病例特点进行总结。 结果 3例患者均表现为进行性加重的肌肉无力症状,完善肌肉活检诊断为杆状体肌病,合并M蛋白,给予行自体造血干细胞移植治疗有效。 结论 散发的晚发型成人杆状体肌病是一种罕见的、亚急性进展的肌病,常合并M蛋白,针对清除M蛋白的治疗是有效的。  相似文献   
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目的探讨“1+X”证书制度下生理学教学改革效果。方法根据职业教育教改精神和文献调研结果,对高职护理专业进行生理学教学改革。结果以岗位需求为量度确定教学目标,以“必需、够用”为原则拟定教学内容,将课程教学与护理过程对接,紧扣“1+X”证书制度,通过职教云平台建设生理学教学资源,融入思政内容,突出技能训练,有效开展基于护理过程的线上线下教学。结论2018级护理专业学生生理学考试成绩与2017级比较,平均分提高4.5分,及格率提高5.7%;参加河南省首届“1+X”老年照护职业技能等级考试的学生,技能考核通过率为100.0%,理论考试通过率为97.8%。  相似文献   
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Wu  Dan  Chen  Mengya  Chen  Shile  Zhang  Shimin  Chen  Yongheng  Zhao  Qian  Xue  Ke  Xue  Feng  Chen  Xiaosong  Zhou  Min  Li  Hao  Zheng  Jie  Le  Yunchen  Cao  Hua 《Clinical rheumatology》2022,41(10):3107-3117
Clinical Rheumatology - Extrahepatic tryptophan (Trp)-kynurenine (Kyn) metabolism via indoleamine 2,3-dioxygenase 1 (IDO1) induction was found to be associated with intrinsic immune regulation....  相似文献   
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摘要: 目的 系统评价注射用头孢哌酮钠/舒巴坦钠(商品名:舒普深)在中国治疗临床感染的有效性和安全性。 方法 系 统检索万方、中国知网、维普、SinoMed、PubMed和Cochrane Library数据库,收集1978年至2019年7月4日公开发表的关于头孢 哌酮/舒巴坦在中国治疗临床感染方面的文献,按照纳入排除标准进行筛选,使用Stata 15.0和SAS 9.4软件进行荟萃(Meta)分析。 主要结局指标包括临床有效率与痊愈率,次要结局指标包括细菌清除率(株)与不良事件发生率。 结果 最终纳入110篇文献,其 中有82篇、87篇分别纳入有效率和痊愈率的Meta分析。结果显示,头孢哌酮/舒巴坦治疗临床感染的总有效率为80.3% [95%置信 区间(CI): 77.4%~83.0%],痊愈率为50.1% (95%CI: 45.1%~55.1%)。共38项研究报告了细菌清除率,结果显示细菌清除率为81.1% (95%CI: 76.9%~84.9%)。62篇文献报告治疗中发生的不良事件例数,合计不良事件的发生率为7.4% (95%CI: 6.1%~8.9%),包括 血液系统不良事件、胃肠道不良事件、肝肾功能损害及皮肤不良事件等。与其他对照药物相比,头孢哌酮/舒巴坦治疗临床感染 的有效性和安全性良好。 结论 头孢哌酮/舒巴坦的临床应用效果较为可观,对治疗临床感染具有较高的价值,安全性好。但 临床应注意合理用药,加强对头孢哌酮/舒巴坦的不良事件监测,减少不良事件。  相似文献   
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