The Impact of Dense Breasts on the Stage of Breast Cancer at Diagnosis: A Review and Options for Supplemental Screening

The purpose of breast cancer screening is to find cancers early to reduce mortality and to allow successful treatment with less aggressive therapy. Mammography is the gold standard for breast cancer screening. Its efficacy in reducing mortality from breast cancer was proven in randomized controlled trials (RCTs) conducted from the early 1960s to the mid 1990s. Panels that recommend breast cancer screening guidelines have traditionally relied on the old RCTs, which did not include considerations of breast density, race/ethnicity, current hormone therapy, and other risk factors. Women do not all benefit equally from mammography. Mortality reduction is significantly lower in women with dense breasts because normal dense tissue can mask cancers on mammograms. Moreover, women with dense breasts are known to be at increased risk. To provide equity, breast cancer screening guidelines should be created with the goal of maximizing mortality reduction and allowing less aggressive therapy, which may include decreasing the interval between screening mammograms and recommending consideration of supplemental screening for women with dense breasts. This review will address the issue of dense breasts and the impact on the stage of breast cancer at the time of diagnosis, and discuss options for supplemental screening.     

Clinical imaging of macular pigment optical density and spatial distribution

Clinical research continues to provide an increasing number of studies that reveal an association between macular pigment optical density (MPOD) and both visual function and ocular health. As a result, there is a growing need for repeatable, accurate measures of MPOD that can describe peak optical density as well as spatial distribution. Measurement of MPOD in a research setting has an established history encompassing a number of both objective and subjective techniques. Transition of these techniques to a clinical setting has produced an array of commercial devices using three primary methods: heterochromatic flicker photometry, fundus autofluorescence and fundus reflectometry. The inherent differences among the techniques create difficulty in making direct comparisons between MPOD measurement devices. Understanding the limitations of each technique is critical in the clinical interpretation of MPOD results. Here, both the objective and subjective methods of MPOD measurement are reviewed with emphasis on the commercially available devices used in clinical settings.     

Biomechanical profile of the cornea in primary congenital glaucoma

Purpose: The aim of our study was to investigate the biomechanical properties of the cornea in primary congenital glaucoma (PCG) and to identify the potential ocular determinants, which affect the corneal biomechanical metrics. Methods: Corneal hysteresis (CH), corneal resistance factor (CRF) and central corneal thickness (CCT) were measured in 26 patients with PCG (40 eyes) with the aid of ocular response analyser. In vivo laser‐scanning confocal microscopy was used for the estimation of stromal keratocyte density (KD) and the evaluation of corneal endothelium. Twenty normal subjects (40 eyes) served as controls. Student’s t‐test and Pearson’s correlation coefficients were used for statistical analysis. p Values <0.05 were considered statistically significant. Results: Corneal hysteresis, CRF and CCT were significantly reduced in patients with PCG (all p < 0.05). Corneal hysteresis and CRF negatively correlated with the corneal diameter in both groups (r₁ = ?0.53, r₂ = ?0.66, p < 0.001 for CH and r₁ = ?0.61, r₂ = ?0.69, p < 0.001 for CRF). Moreover, we identified a significant correlation between CH and CRF with CCT in both groups (r₁ = 0.51, r₂ = 0.48, p < 0.001 for CH and r₁ = 0.45, r₂ = 0.44, p < 0.001 for CRF). Mean KD was significantly reduced both in the anterior and posterior corneal stroma in patients with PCG (764 ± 162 and 362 ± 112 cells/mm², respectively) compared with controls (979 ± 208 and 581 ± 131 cells/mm², respectively) (p < 0.001). There was no significant correlation between the keratocyte density in anterior and/or posterior stroma and CH or CRF in any group (r₁ = 0.29, r₂ = 0.31, p < 0.06). Mean endothelial cell density was also significantly reduced in PCG group (2920 ± 443 cells/mm²) compared with control group (3421 ± 360 cells/mm²) (p < 0.001). Pleomorphism and polymegalism were significantly increased in corneal endothelium of patients with PCG. Conclusions: Our results showed a significant reduction in CH and CRF in PCG. Both CH and CRF were negatively correlated with corneal diameter. A significant correlation of CH and CRF with CCT was identified in both groups. Keratocyte density was decreased in PCG, but did not have a significant impact on CH and CRF. Mean endothelial density was also decreased in PCG. Our results suggest that reduced CCT and increased corneal diameter are major ocular determinants for the modified corneal biomechanical profile in PCG, while cellular alterations in corneal stroma and endothelium have no significant biomechanical impact.     

四种补肾中药对去卵巢大鼠骨质疏松骨形态的作用

目的 比较骨碎补、锁阳、淫羊藿和狗脊４种补肾中药对去卵巢（ＯＶＸ）大鼠骨质疏松的作用。方法 将５４只３月龄雌性Ｗｉｓｔａｒ大鼠随机分成模型组和中药治疗组。模型组包括非手术组、假手术组和去卵巢组,每组１０只;中药组包括骨碎补组、锁阳组、淫羊藿组和狗脊组,每组６只。去卵巢手术后１周,中药组分别用上述４种中药喂养,８周后放血外死全部小鼠,用骨形态主坦学方法比较４种中药对ＯＶＸ大鼠骨质疏松的防治作用。结果     

Effects of traditional herbal medicine, Hwaotang, on atherosclerosis using the spontaneous familial hypercholesterolemia model, Kurosawa and Kusanagi-hypercholesterolemic rabbits and the venous thrombosis rats

Hwaotang (HOT), a traditional Korean medicinal formulation, is a dried decoctum of a mixture of seven herbal medicines, consisting of Angelica gigantis Radix, Rehmanniae Radix, Paeoniae Radix, Ciniamomi Cortex, Cnidii Rhizoma, Persicae Semen and Carthami Flos. In the present study, the inhibitory effects and anti thrombic properties of HOT on the progression of atherosclerotic lesions were studied using the spontaneous familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits and rats. Changes in blood chemistry, pathology and low-density lipoprotein (LDL) oxidation were measured in a control and HOT group. In the control group, the area of atheromatous plaques of the aorta progressed between week 12 (36.65%) and week 14 (46.22%). This progression of atherosclerotic lesions did not occur in the HOT-treated group after 12 (24.24%) and 14 (23.34%) weeks. Antioxidative effects on LDL were seen in the HOT in weeks 12 and 14. HOT improved the hypercholesterolemia in the KHC rabbits. On the other hand, HOT and five of the seven herbs, except Cnidii Rhizoma and Carthami Flos, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. However, Ciniamomi Cortex showed a very weak inhibitory effect on the endotoxin-induced hepatic venous thrombosis. The extract also inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In conclusion, these results suggest that HOT has inhibitory effects on the development of atheromatous plaque formation in spontaneous FH rabbits. It is also suggested that the antioxidative effects of HOT on LDL led to the beneficial effects observed in this study. The protection by HOT and its herbs on the artificially induced ischemic infarction might be related to their inhibitory effects on disseminated intravascular coagulation, platelet coagulation and thrombotic action.     

Physiologic Transdermal Estradiol Replacement Mimics Effects of Endogenous Estrogen on Bone Outcomes in Hypoestrogenic Women with Anorexia Nervosa

Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14–25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite element analysis to estimate strength. Results: Groups did not differ for age. Median baseline BMI z-scores were −1.13 (−1.58, −0.38) in AN-E+ vs. 0.08 (−0.40, 0.84) in HC (p < 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue mineral density, cortical vBMD, and failure load increased (p = 0.01; p = 0.02; p = 0.004 respectively) over 12 months in AN-E+ compared to HC. Conclusions: With physiologic estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for estrogen replacement effectively mimics the effects of endogenous estrogen on bone structure and estimated strength.     

小儿尿道下裂尿道板组织中雌激素受体及微血管密度的表达及临床意义

目的 探讨尿道下裂患儿尿道板组织和尿道部皮肤组织中雌激素受体(ER)和微血管密度(MVD)的表达及意义.方法 选取2013年6月-2015年1月天津儿童医院收治的尿道下裂手术患儿30例,术中分别取部分尿道板和尿道部皮肤组织,检测不同组织中ER及MVD的表达及分布情况.结果 2组均检测到ER及MVD的表达.尿道板组织与尿道部皮肤组织中ER表达水平比较差异无统计学意义(P＞0.05),尿道板组织中MVD低于尿道部皮肤组织(P＜0.05).结论 尿道板组织和尿道部皮肤组织ER含量接近,可能与尿道发育异常有关;尿道板组织中存在微血管分布,为保留尿道板的尿道成形术提供了理论依据;尿道板组织内MVD显著降低,可能为术后发生尿瘘的原因之一.     

两种指标计算住院病人抗菌药物使用强度的适用性比较

目的：比较采用实际占用总床日数和收治病人人数天数计算住院病人抗菌药物使用强度（antibacterial use density, AUD）的准确性,以确定一个适用性更高的AUD计算方法。方法：分别使用实际占用总床日数和收治病人人数天数（即抽样时间段内出院人数×平均住院天数）计算上海市公共卫生临床中心2009-2011年每年,以及2012年1-3月每月住院病人的AUD,记为AUD1和AUD2,比较月度AUD1和AUD2、年度AUD1和AUD2的离散度。结果：月度AUD1的离散度显著小于月度AUD2离散度,年度AUD1和年度AUD2的离散度相差不大。结论：与收治病人人数天数相比,使用实际占用总床日数计算AUD适用性更佳,更能真实反映住院病人抗菌药物使用水平。     

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release

Aim： Paeonol （2＇-hydroxy-4＇-methoxyacetophenone） from Cortex moutan root is a potential therapeutic agent for atherosclerosis. This study sought to investigate the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular endothelial cells （VECs） in vitro.
Methods： VECs were isolated from rat thoracic aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with ox-LDL for another 24 h. The expression of microRNA-21 （miR-21） and PTEN in VECs was analyzed using qRT-PCR. The expression of PTEN protein was detected by Western blotting. TNF-α release by VECs was measured by ELISA.

Results： Ox-LDL treatment inhibited VEC growth in dose- and time-dependent manners （the value of IC50 was about 20 mg/L at 24 h）. Furthermore, ox-LDL （20 mg/L） significantly increased miR-21 expression and inhibited the expression of PTEN, one of downstream target genes of miR-21 in VECs. In addition, ox-LDL （20 mg/L） significantly increased the release of TNF-α from VECs. Pretreatment with paeonol increased the survival rate of ox-LDL-treated VECs in dose- and time-dependent manners. Moreover, paeonol （120 μmol/L） prevented ox-LDL-induced increases in miR-21 expression and TNF-α release, and ox-LDL-induced inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR-21 bound directly to PTEN＇s 3＇-UTR, thus inhibiting PTEN expression. In ox-LDL treated VECs, transfection with a miR-21 mimic significantly increased miR-21 expression and inhibited PTEN expression, and attenuated the protective effects of paeonol pretreatment, whereas transfection with an miR-21 inhibitor significantly decreased miR-21 expression and increased PTEN expression, thus enhanced the protective effects of paeonol pretreatment.

Conclusion： miR-21 is an important target of paeonol for its protective effects against ox-LDL-induced VEC injury, which may play critical roles in development of atherosclerosis.     

银杏叶提取物体外对铜离子诱导的人血清低密度脂蛋白氧化修饰的抑制作用(英文)

本文在体外对EGb761能否抑制钢离子诱导的人血清低密度脂蛋白氧化修饰进行了研究。低密度脂蛋白（LDL）用EGb76140,80,160mg·L(-1)‘预处理1h,然后用CuSO410μmol·(-1)氧化修饰10h。结果表明LDL被钢离子氧化修饰后低密度脂蛋白中维生素E（VE）被耗竭,丙二醛（MDA）及自身荧光物质（LF）含量升高,载脂蛋白B（apoB）的电泳迁移速率加快。EGb761剂量依赖性地抑制VE的含量降低和MDA及自身荧光物质的含量升高,载脂蛋白B的电泳迁移速率依次减慢。可见在体EGb761能抑制钢离子诱导的人血清低密度脂蛋白氧化修饰。