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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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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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目的 探究慢性炎性疼痛对小鼠肠道菌群多样性和结构的影响。方法 选取SPF级雌性C57BL/6J小鼠12只,随机分为CFA组和Mock组,每组6只;Mock组右后足底皮下注射50μl的0.9%氯化钠溶液,CFA组右后足底皮下注射50μl的CFA作为慢性炎性疼痛模型组。2周后,安乐死小鼠,解剖后取结肠内粪便,组内两只小鼠结肠内粪便进行混样,采用16S rRNA高通量基因测序技术检测分析肠道菌群多样性和结构。结果 两组小鼠在肠道菌群构成上差异明显。与Mock组相比,CFA组肠道菌群丰富度及多样性降低;门水平上,厚壁菌门和TM7丰度升高;科、属水平上,气球菌属、乳酸杆菌属和脱硫弧菌属丰度显著升高,嗜冷杆菌属、普雷沃氏菌属、颤螺菌属和双歧杆菌属丰度明显降低;从门到属主要分类等级上,发现的生物标志物较多。结论 慢性炎性疼痛的小鼠肠道菌群结构尤其是优势菌群结构发生了明显变化,这些数据可为慢性炎性疼痛导致的微生态失衡的治疗及通过“肠-脑轴”改善患者消极情绪提供依据。  相似文献   
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目的探讨经尿道膀胱肿瘤二次电切术(Re-TURBT)在降低Ta和T1期非肌层浸润性膀胱癌(NMIBC)电切术后肿瘤复发率的临床价值。 方法回顾性分析2015年2月至2018年11月我院86例诊断为Ta和T1期的NMIBC患者。患者接受单次经尿道膀胱肿瘤电切术为对照组(40例),接受二次经尿道膀胱肿瘤切除术为观察组(46例),两组患者首次电切术中均联合了吉西他滨即刻膀胱灌注化疗。统计观察组二次电切的阳性率及肿瘤分期分级变化情况,同时比较两组患者术后2年内的肿瘤复发及进展情况。 结果两组患者年龄、性别、吸烟史、肿瘤最大径、肿瘤个数、首次电切病理分期比较差异无统计学意义(P>0.05)。观察组二次电切术后的病理结果显示,11例(23.91%)检出残余癌,5例出现临床分期升级,4例病理分级升级。观察组术后2年总复发率低于对照组(P<0.05)。两组术后2年总进展率差异无统计学意义(P>0.05)。 结论Re-TURBT可明显降低Ta和T1期NMIBC电切术后肿瘤复发率,同时可获得更准确的肿瘤分期,具有一定的临床价值。  相似文献   
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Journal of the Association for Research in Otolaryngology - Cochlear implant (CI) users show limited sensitivity to the temporal pitch conveyed by electric stimulation, contributing to impaired...  相似文献   
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