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1.
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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尚京迎  谢纪珍  王群  杨成勇 《中国药事》2022,36(12):1363-1368
目的:通过分析山东省药品许可换证检查过程中发现的一些普遍性问题,为监管部门科学监管与企业持续提升质量管理体系提出建议与对策。方法:统计169家药品批发企业换证检查中发现的缺陷项目,并分析企业普遍存在的问题。结果:药品批发企业换证现场检查常见问题主要集中在质量管理体系文件、储存与养护、人员与培训、设施与设备方面。结论:监管部门应加强监督检查力度,做好日常监管,并加强法律法规的宣贯工作;企业在药品经营过程中,各岗位人员应全员参与,按照制度履行职责。通过提高企业全体员工的质量意识,促进企业规范经营和健康发展。  相似文献   
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<正>克兰费尔特综合征(Klinefelter’s syndrome,KS)简称克氏综合征,属于先天性疾病。由于额外增加至少1条X染色体导致睾丸曲细精管发育异常,KS表现为青春发育不完全和精子生成障碍。迄今为止,对于KS合并中枢性性早熟(central precocious puberty,CPP)或青春早发育快进展,国内外鲜有报道。本文报道1例47,XXY KS合并青春早发育快进展患者,并通过文献复习探讨其可能的发病机制和治疗措施,以提高对该病的认识。  相似文献   
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Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose was to ascertain if any relation exists between the elevated intraocular pressure (IOP) in patients with...  相似文献   
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Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.  相似文献   
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Journal of Developmental and Physical Disabilities - Caregiver support is an important contextual factor in the daily functioning of children with cerebral palsy (CP), but few studies have examined...  相似文献   
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AIM: To investigate fluctuation of intraocular pressure (IOP) and seasonal variation of 24-hour IOP during one year in healthy participants METHODS: Totally 13 young healthy volunteers participated in this study. IOP was measured with Canon TX-20 at about 8:00-9:00 a.m. from Monday to Friday every week for a whole year. They also underwent 24-hour IOP examination every three months. Blood pressure, heart rate, temperature, humidity, atmosphere pressure, sunshine duration and other environment parameters were recorded. RESULTS: The yearly fluctuation curve showed IOP in the summer months were lower than other seasons. In the multivariable generalized estimating equation analysis, IOP had a negative correlation with both temperature and sunshine duration (P<0.05). There also was a seasonal effect on 24-hour IOP. However, all intraclass correlation coefficients values of minimum, maximum and average of the 24-hour IOP and each individual IOP were less than 0.30. CONCLUSION: IOP is trend to be higher in cold days than warm days. IOP have negative association with both environmental temperature and duration of sunshine. On a season-to-season basis, 24-hour IOP is not highly reproducible in healthy volunteers.  相似文献   
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