Dual-energy contrast-enhanced digital mammography: Glandular dose estimation using a Monte Carlo code and voxel phantom

PurposeTo estimate the mean glandular dose of contrast enhanced digital mammography, using the EGSnrc Monte Carlo code and female adult voxel phantom.MethodsAutomatic exposure control of full field digital mammography system was used for the selection of the X-ray spectrum and the exposure settings for dual energy imaging. Measurements of the air-kerma and of the half value layers were performed and a Monte Carlo simulation of the digital mammography system was used to compute the mean glandular dose, for breast phantoms of various thicknesses, glandularities and for different X-ray spectra (low and high energy).ResultsFor breast phantoms of 2.0–8.0 cm thick and 0.1–100% glandular fraction, CC view acquisition, from AEC settings, can result in a mean glandular dose of 0.450 ± 0.022 mGy −2.575 ± 0.033 mGy for low energy images and 0.061 ± 0.021 mGy – 0.232 ± 0.033 mGy for high energy images. In MLO view acquisition mean glandular dose values ranged between 0.488 ± 0.007 mGy – 2.080 ± 0.021 mGy for low energy images and 0.065 ± 0.012 mGy – 0.215 ± 0.010 mGy for high energy images.ConclusionThe low kV part of contrast enhanced digital mammography is the main contributor to total mean glandular breast dose. The results of this study can be used to provide an estimated mean glandular dose for individual cases.     

New derivatives of lupane triterpenoids disturb breast cancer mitochondria and induce cell death

Novel cationic dimethylaminopyridine derivatives of pentacyclic triterpenes were previously described to promote mitochondrial depolarization and cell death in breast and melanoma cell lines. The objective of this work was to further investigate in detail the mechanism of mitochondrial perturbations, correlating those effects with breast cancer cell responses to those same agents. Initially, a panel of tumor and non-tumor cell lines was grown in high-glucose or glucose-free glutamine-containing media, the later forcing cells to synthesize ATP by oxidative phosphorylation only. Cell proliferation, cell cycle, cell death and mitochondrial membrane polarization were evaluated. Inhibition of cell proliferation was observed, accompanied by an arrest in the G1-cell cycle phase, and importantly, by loss of mitochondrial membrane potential. On a later time-point, caspase-9 and 3 activation were observed, resulting in cell death. For the majority of test compounds, we determined that cell toxicity was augmented in the galactose media. To investigate direct evidences on mitochondria isolated rat liver mitochondria were used. The results showed that the compounds were strong inducers of the permeability transition pore. Confirming our previous results, this work shows that the novel DMAP derivatives strongly interact with mitochondria, resulting in pro-apoptotic signaling and cell death.     

Finite element analysis of different loading conditions for implant-supported overdentures supported by conventional or mini implants

The effect of implants’ number on overdenture stability and stress distribution in edentulous mandible, implants and overdenture was numerically investigated for implant-supported overdentures. Three models were constructed. Overdentures were connected to implants by means of ball head abutments and rubber ring. In model 1, the overdenture was retained by two conventional implants; in model 2, by four conventional implants; and in model 3, by five mini implants. The overdenture was subjected to a symmetrical load at an angle of 20 degrees to the overdenture at the canine regions and vertically at the first molars. Four different loading conditions with two total forces (120, 300 N) were considered for the numerical analysis. The overdenture displacement was about 2.2 times higher when five mini implants were used rather than four conventional implants. The lowest stress in bone bed was observed with four conventional implants. Stresses in bone were reduced by 61% in model 2 and by 6% in model 3 in comparison to model 1. The highest stress was observed with five mini implants. Stresses in implants were reduced by 76% in model 2 and 89% increased in model 3 compared to model 1. The highest implant displacement was observed with five mini implants. Implant displacements were reduced by 29% in model 2, and increased by 273% in model 3 compared to model 1. Conventional implants proved better stability for overdenture than mini implants. Regardless the type and number of implants, the stress within the bone and implants are below the critical limits.     

SHCBP1:乳腺癌治疗候选靶点和潜在预后标志物

探讨SHCBP1在乳腺癌及其不同亚型中的表达特征和预后价值。利用Oncomine, bc-GenExMiner v4.2, Kaplan-Meier plotter, GSE41994及STRING数据库分析乳腺癌病人SHCBP1的mRNA表达水平及其与乳腺癌患者生存率的相关性等。结果:(1)乳腺癌组织中SHCBP1的mRNA水平明显高于正常组织样本,但不同分子亚型的乳腺癌患者中SHCBP1的表达水平不同;(2)SHCBP1表达升高可导致Luminal A亚型更短的无转移生存期(Distant metastasis-free survival,DMFS)和无病生存期(Disease-free survival, DFS);(3)在雌激素受体阳性(ER+)、孕酮受体阳性(PR+)亚型、仅接受辅助化疗、仅接受辅助化疗的ER(+)与接受包括或排除内分泌治疗乳腺癌患者中,SHCBP1表达升高则无复发生存率(Relapse-free survival,RFS)显著缩短;(4)SHCBP1和CDC45 mRNA表达水平之间呈正相关,并可能与KIF23等10种蛋白相互作用。结论:SHCBP1是一种很有前景的乳腺癌预后指标和潜在的治疗靶点。     

MicroRNA-221/222对乳腺癌MDA-MB-231/DOX细胞阿霉素耐药性的影响

目的:探讨微小RNA-221/222(miR-221/222)对乳腺癌MDA-MB-231/阿霉素(DOX)细胞DOX耐药性的影响。方法:采用脂质体法转染miR-221/222抑制物(miR-221/222 inhibitor)至MDA-MB-231/DOX细胞内(Inhibitor组),同时设立空白对照组和转染无关序列的阴性对照组,采用实时荧光定量PCR (qRT-PCR)检测MDA-MB-231细胞株及MDA-MB-231/DOX细胞株的miR-221/222表达水平及转染效率;CCK-8法检测转染48 h后MDA-MB-231/DOX细胞对DOX药物敏感性的变化;流式细胞术(FCM)检测转染MDA-MB-231/DOX细胞的细胞凋亡率;蛋白免疫印迹实验(WB)检测转染后MDA-MB-231/DOX细胞内促凋亡蛋白p53上调凋亡调控因子(PUMA),Bcl2蛋白修饰因子(BMF)以及细胞周期蛋白激酶抑制因子p27(p27Kip1)的表达情况。结果:MDA-MB-231/DOX细胞中的miR-221/222表达水平高于亲本MDA-MB-231细胞(P0.05);MDA-MB-231/DOX细胞转染miR-221/222 inhibitor 96 h后,miR-221/222的表达水平低于空白对照组和阴性对照组(P0.05);与空白对照组相比,MDA-MB-231/DOX细胞转染miR-221/222 inhibitor 48h后,DOX继续处理48 h后,细胞的凋亡率明显升高,且细胞内的促凋亡蛋白PUMA,BMF以及p27Kip1的表达均增加(P0.05);DOX对inhibitor组耐药细胞的半数抑制浓度(IC50)显著低于空白对照组细胞及阴性对照组(P0.05)。结论:miR-221/222能够增加MDA-MB-231/DOX细胞对DOX的耐药性,这可能与下调促凋亡蛋白的表达有关;降低miR-221/222水平可诱导MDA-MB-231/DOX凋亡,并且上调促凋亡蛋白的表达,从而部分逆转MDA-MB-231/DOX对DOX的耐药性。     

乳腺癌患者改良根治术后生活质量调查及复发转移的影响因素分析

目的:调查乳腺癌患者改良根治术后生活质量,并对其复发转移的影响因素进行分析。方法:选取2012年6月～2014年6月期间于我院行改良根治术的乳腺癌患者197例,于术后3个月、术后6个月、术后12个月采用乳腺癌患者生命质量测定量表(FACT-B)评价患者生活质量。采用我院自制的调查问卷统计患者基本治疗情况,分析乳腺癌改良根治术后复发转移的影响因素。结果:本研究中,共发放197份问卷调查,回收195份,回收率为98.98%(195/197)。其中195例患者中有73例发生复发转移(复发转移组),122例未发生复发转移(未复发转移组)。195例乳腺癌患者术后3个月、术后6个月、术后12个月社会/家庭状况、生理状况、功能状况、情感状况、附加关注条目、总体生活质量等项目评分呈递增趋势(P0.05)。多因素Logistic回归分析显示,病理类型为浸润性非特殊性癌、肿瘤大小≥2 cm、临床分期为Ⅲ期、激素受体为ER及PR均阴性均是乳腺癌改良根治术后复发转移的独立危险因素(P0.05),而采用放化疗、联合化疗方案、内分泌治疗以及p53蛋白阳性表达是乳腺癌改良根治术后复发转移的独立保护因素(P0.05)。结论:乳腺癌患者行改良根治术后生活质量呈动态变化,其术后复发转移影响因素为病理类型、临床分期、肿瘤大小、激素受体、化疗方案、p53蛋白、内分泌治疗及放化疗。     

17号染色体不同倍体与乳腺癌临床病理特征的相关性

摘要 目的：探讨17号染色体不同倍体与乳腺癌临床病理特征的相关性。方法：选取2018年1月至2019年12月确诊为乳腺癌的患者78例(乳腺癌组)与乳腺良性肿瘤患者78例(良性组),采用原位荧光杂交检测所有患者的病灶组织染色体不同倍体情况,分析患者的临床病理特征并进行相关性分析。结果：乳腺癌组17号染色体的多倍体率为85.9 %,显著高于良性组(3.8 %,P<0.05)。不同年龄、性别、发病位置、病理类型乳腺癌患者的17号染色体多倍体率对比差异无统计学意义(P>0.05),不同淋巴结转移、组织学分化、临床分期、ER阳性、PR阳性患者的17号染色体多倍体率对比差异具有统计学意义(P<0.05)。Pearson分析显示17号染色体多倍体率与乳腺癌患者的淋巴结转移、组织学分化、临床分期、ER阳性、PR阳性存在显著相关性(P<0.05);多因素Logistic回归分析显示淋巴结转移、组织学分化、临床分期、ER阳性、PR阳性都为17号染色体多倍体的主要危险影响因素(P<0.05)。结论：乳腺癌患者多伴随有17号染色体多倍体,与其患者的淋巴结转移、组织学分化、临床分期、ER阳性、PR阳性等临床病理特征显著相关。     

Early host–microbe interaction in a peri‐implant oral mucosa‐biofilm model

The host‐microbe relationship is pivotal for oral health as well as for peri‐implant diseases. Peri‐implant mucosa and commensal biofilm play important roles in the maintenance of host‐microbe homeostasis, but little is known about how they interact. We have therefore investigated the early host‐microbe interaction between commensal multispecies biofilm (Streptococcus oralis, Actinomyces naeslundii, Veillonella dispar, Porphyromonas gingivalis) and organotypic peri‐implant mucosa using our three‐dimensional model. After 24 hr, biofilms induced weak inflammatory reaction in the peri‐implant mucosa by upregulation of five genes related to immune response and increased secretion of IL‐6 and CCL20. Biofilm volume was reduced which might be explained by secretion of β‐Defensins‐1, ‐2, and CCL20. The specific tissue reaction without intrinsic overreaction might contribute to intact mucosa. Thus, a relationship similar to homeostasis and oral health was established within the first 24 hr. In contrast, the mucosa was damaged and the bacterial distribution was altered after 48 hr. These were accompanied by an enhanced immune response with upregulation of additional inflammatory‐related genes and increased cytokine secretion. Thus, the homeostasis‐like relationship was disrupted. Such profound knowledge of the host‐microbe interaction at the peri‐implant site may provide the basis to improve strategies for prevention and therapy of peri‐implant diseases.