Purification of blood from microparticles while maintaining its suitability for autotransfusion provides a revolutionary support for advanced healthcare through circulatory system of blood flows. However, there is a great challenge in the separation of particles from blood physically with high efficiency. Here, we proved a novel approach for whole blood treatment of microparticle separation utilizing a three-dimensional microfluidic chip with helical structures of tubular channels. The chips with helical structures characterized by spiral diameters and pitches are fabricated with flexible silicon-based tubes with different inner diameters in which photolithography is not required. By controlling Reynolds and Dean numbers to generate appropriate stable Dean flow along the tubular channels, microparticles with diameters from 15 to 30 mu m are separated directly from untreated whole blood with about 10% blood loss, and the free-hemoglobin concentration after separation remains in a safe level for further clinical transfusion. Two distinct patterns of particle accumulation in the cross section of microtubes are observed. It is also interesting to find that different from many practices that lyse red blood cells before particle or cell sorting, the intensive cell-particle interactions in whole blood facilitate particle focusing to regions closer to channel walls than in pure liquid without red blood cells. This label-free particle separation method, based on hydrodynamical interactions among the particles and deformable blood cells in stable Dean vortexes of helical tubular microfluidic chips, not only paves the way for innovative healthcare using functional microparticles but also enlightens the sorting of nucleated cells separation from whole blood biophysically.

Juvenile gigantomastia is a rare condition showing progressive breast enlargement during puberty. Here, we report a rare case of a 12-year-old female patient who developed rapid bilateral breast hypertrophy following menarche. The patient has complex family history of consanguineous marriage and individual history of suspected Madelung's disease during her infancy. After examinations and muti-department consultation, we did bilateral mastectomy to address the severe breast enlargement, and planned to perform breast reconstruction surgery after complete sexual maturity. The histopathological investigations revealed the presence of pseudo angiomatous stromal hyperplasia (PASH). Genetic analysis was conducted to explore potential hereditary contributions to the condition. During six months of follow-up period, no new breast lumps or enlargement occurred, and the patient had no postoperative complications such as infection and hematoma.

The intrinsic physical and mechanical properties of red blood cells (RBCs), including their geometric and rheological characteristics, can undergo changes in various circulatory and metabolic diseases. However, clinical diagnosis using RBC biophysical phenotypes remains impractical due to the unique biconcave shape, remarkable deformability, and high heterogeneity within different subpopulations. Here, we combine the hydrodynamic mechanisms of fluid-cell interactions in micro circular tubes with a machine learning method to develop a relatively high-throughput microfluidic technology that can accurately measure the shear modulus of the membrane, viscosity, surface area, and volume of individual RBCs. The present method can detect the subtle changes of mechanical properties in various RBC components at continuum scales in response to different doses of cytoskeletal drugs. We also investigate the correlation between glycosylated hemoglobin and RBC mechanical properties. Our study develops a methodology that combines microfluidic technology and machine learning to explore the material properties of cells based on fluid-cell interactions. This approach holds promise in offering novel label-free single-cell-assay-based biophysical markers for RBCs, thereby enhancing the potential for more robust disease diagnosis.

Triple-negative breast cancer (TNBC), a highly aggressive form of breast cancer, currently lacks targeted therapies and is associated with high recurrence rates in medical practice. In this study, the effectiveness of a specially developed magnetic nanodrug, namely doxorubicin (DOX)-loaded Fe3O4 vortex magnetic nanoannulars coated with a cancer cell membrane (DOX-VMAs@CM), against cancer under a varying low-frequency magnetic field (MF), is investigated. This advanced nanodrug can specifically target and accumulate in tumors. Additionally, it considerably improves tumor suppression compared with that of DOX chemotherapy alone, indicating the possibility of homologous targeting of the cancer cell membrane and the vibrating effect of the MF. The DOX-VMAs@CM nanoparticles (NPs) exhibit exceptional safety characteristics because of their ability to specifically target tumors. The results of RNA sequencing suggest that the potential mechanisms may involve cellular respiration, cell cycle, and ferroptosis regulation. Altogether, chemotherapy is successfully optimized by implementing a delivery system and MF intervention, and the developed DOX-VMAs@CM NPs hold significant potential for use in the clinical treatment of TNBC.

Triple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer, currently lacks a targeted therapy and has a high clinical recurrence rate. The present study reports an engineered magnetic nanodrug based on Fe3 O4 vortex nanorods coated with a macrophage membrane loaded with doxorubicin (DOX) and Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) siRNA. This novel nanodrug displays excellent tissue penetration and preferential tumor accumulation. More importantly, it significantly increases tumor suppression compared to chemotherapy, suggesting the synergistic activity of the combination of doxorubicin and EZH2-inhibition. Importantly, owing to tumor-targeted delivery, nanomedicine shows an excellent safety profile after systemic delivery, unlike conventional chemotherapy. In summary, chemotherapy and gene therapy are combined into a novel magnetic nanodrug carrying doxorubicin and EZH2 siRNA, which shows promising clinical application potential in TNBC therapy.

Breast cancer is a malignant tumor that seriously endangers women’s health worldwide and is the number one cancer in terms of incidence. In recent years, although the research on interdisciplinary drug delivery systems that combine nanotechnology and medical oncology is fully developed with significant efficacy, such as nano-based drug delivery systems (NDDs), the current clinical translation rate of drug delivery systems is not high. Moreover, NDDs are designed as carrier systems for drug delivery to targets, prolonging drug circulation time in vivo, improving targeting, reducing tumor resistance, and providing new avenues for the prevention and treatment of many diseases. Herein, the current approaches of several commonly used carrier nanoparticles are discussed, mainly including liposomes, polymeric micelles, metals, inorganic nanoparticles and nanohydrogels, as well as composite NDDS in breast cancer treatment, including their properties, system design, major innovations, and applications in clinical settings.

Nanomedicine In article number 2301307, Yan Liu, Xiang Li, and co-workers report a novel engineered magnetic nanodrug based on Fe3O4 vortex nanorods coated with a macrophage membrane loaded with doxorubicin and EZH2 siRNA. This novel nanodrug has synergistic activity chemotherapy and gene therapy, which shows promising clinical application potential in triple-negative breast cancer (TNBC) therapy.

As a drug carrier, the properties of magnetic nanoparticles for drug loading are significant. In this letter, three different shapes of magnetic nanoparticles for drug carrier systems were compared. We synthesized Fe3O4 magnetic nanospheres, nanorings and nanotubes, and plyethylene glycol was used as a surface modifier for drug loading. The structure characterization of three different shapes of Fe3O4 nanoparticles was elucidated by electron microscopy, and the composition was analyzed by Fourier transform infrared. The drug loading status and drug release of the three types of nanoparticles with different shapes were tested by Ultraviolet Spectrophometometer. The results show that the hollow Fe3O4 magnetic nanorings and nanotubes have better drug loading capacity and are more suitable for drug carriers, compared with nanospheres.

An amendment to this paper has been published and can be accessed via the original article.

癌症是致死率最高的疾病之一，癌症的治疗一直以来都是临床医学中的重点研究课题。化学治疗作为最常采用的治疗方法有效却也存在许多弊端，因为大多数化疗药物缺乏选择性和靶向性，会对人体的健康造成不必要的影响，因此纳米药物递送系统在治疗癌症的研究中发挥着重要的作用。而磁性纳米颗粒作为纳米药物递送系统的其中一类载体，既具有粒径小、比表面积大等纳米材料的一般特点，又具有特殊的磁学性能，经表面修饰后可以连接药物、分子、配体等，在内源或外源性因素的激发下，可以有效地靶向肿瘤细胞并发挥其磁性作用。本文将基于以下几个方面进行综述研究：（1）磁性纳米颗粒作为化疗药物递送系统的载体，结合不同的负载药物对癌症治疗的效果；（2）根据肿瘤微环境中特殊的pH响应机制，分析磁性纳米颗粒药物载体的不同表面修饰对肿瘤细胞的靶向性及药物控释的影响；（3）结合肿瘤对温度变化的敏感性，阐述了利用磁性纳米颗粒对肿瘤进行热磁疗的作用效果；（4）分析了在癌症领域利用磁性载药纳米颗粒进行光声疗法、光热疗法、光动力疗法的作用机制及发展现状。（5）总结了磁性纳米颗粒作为药物载体在癌症治疗领域的发展现状及所面临的问题。为其能够早日在临床医学中得到应用提供了参考。

Uniform hexagonal hematite (α-Fe2O3) nanoplates were prepared via a facile alcohol-thermal reaction without using any template. Each nanoplate is enclosed by (0001) basal planes and {10 $$\bar {1}$$ 2} side surfaces. The phase, size, shape and growth orientation of the resulting product were characterized by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HRTEM).In order to obtain a product with more uniform and stable morphology, on the basis of predecessors' studies, the reaction time was adjusted to a small extent, so that an ideal hexagonal nanoplates was obtained. Magnetite (Fe3O4) nanoplates were obtained through a reduction process without changing the morphology and size of the resulting α-Fe2O3 nanoplates. Detection of transition from α-Fe2O3 to Fe3O4 nanoplates by X-ray photoelectron spectroscopy (XPS).The magnetic properties of these reduced nanoplates were investigated and it was found that these nanoplates have higher coercivity and lower saturation magnetization than many other nanostructured iron oxides. The surface adsorption of nonmagnetic materials and their flake morphology may be the cause of this phenomenon.

The side effects of chemotherapy are mainly the poor control of drug release. Magnetic nanoparticles（MNPs） have super-paramagnetic behaviors which are preferred for biomedical applications such as in targeted drug delivery, besides, in magnetic recording, catalysis, and others. MNPs, due to high magnetization response, can be manipulated by the external magnetic fields to penetrate directly into the tumor, thus they can act as ideal drug carriers. MNPs also play a crucial role in drug delivery system because of their high surface-to-volume ratio and porosity. The drug delivery in tumor therapy is related to the sizes, shapes, and surface coatings of MNPs as carriers. Therefore, in this review, we first summarize the effects of the sizes, shapes, and surface coatings of MNPs on drug delivery, then discuss three types of drug release systems, i.e., p H-controlled, temperature-controlled, and magnetic-controlled drug release systems, and finally compare the principle of passive drug release with that of active drug release in tumor therapy.

Aim Pemetrexed, a new generation antifolate drug, is approved for the treatment for locally advanced or metastatic breast cancer, but factors affecting the efficacy and resistance of it have yet to be fully explicit. ATP-binding cassette transporters have been reported as prognostic and adverse effects predictors of many xenobiotics. This study was designed to explore whether ABC transporters affect pemetrexed resistance and may contribute to treatment regimen optimization for breast cancer. Methods Firstly, the expression of ABC transporters family members was measured in cell lines, thereafter examined the potential role of ABC transporter in conferring resistance to pemetrexed in primary cancer cell lines isolated from 34 breast cancer patients, and then the role of ABCC5 in mediating transport of pemetrexed and apoptosis pathway in MCF-7 cell lines was assessed. Finally, the functions of ABCC5 on therapeutic effect of pemetrexed was evaluated in breast cancer bearing mice. Results The expressions of ABCC2, ABCC4, ABCC5 and ABCG2 were significantly increased in pan-resistance cell lines, and the ABCC5, the most obvious one, was 5.21 times higher than that of the control group. The expression of ABCC5 was inversely correlated with sensitivity (IC 50 ) of pemetrexed (r = 0.741; p <0.010) in breast cancer cell lines from 34 patients. Further, we found expression of ABCC5 influenced the efflux and cytotoxicity of pemetrexed in MCF-7 cell line, and the IC 50 were 0.06 μg/ml and 0.20 μg/ml in ABCC5 knock-down and over-expression cells, respectively. In vivo study, we found ABCC5 affected sensitivity of pemetrexed in breast cancer bearing mice, and the tumor volume was much larger in ABCC5 over-expression group than that in control group (2.7 folds vs 1.2 folds). Conclusions Our results indicated ABCC5 was associated with pemetrexed sensitivity and resistance in vitro and in vivo, and may be a biomarker for regimen optimization of pemetrexed in breast cancer treatment.

目的 建立一种使用微吸管测量具有良好生理活性的循环肿瘤细胞(circulating tumor cells,CTCs)弹性模量的方法.方法 使用商品化的微流控芯片富集血液中具有良好生理活性的CTCs,使用EpCAM抗体确定CTCs,并使用微吸管测量其弹性模量,同时与癌细胞系弹性模量相对比.结果 对于癌细胞系的弹性模量,不仅在不同细胞系间存在较大的差异,在同一细胞系间也存在较大的异质性.血液中CTCs相比于同种癌细胞系属于弹性模量较小的癌细胞.结论 该方法能够获得生理活性较好的CTCs并测量其弹性模量,为进一步研究CTCs力学特性与癌症诊断和治疗预后之间的相关关系,推进癌细胞物理标志物的发展提供细胞力学数据支持.

Background: This study aimed to identify the influence of peripheral lymphocytes on prognosis and find prognostic markers for breast cancer patients. Methods: This study enrolled invasive breast cancer patients and they were followed-up for median 4-years over telephone. Distributions of disease-free survival (DFS) and overall survival (OS) between different levels of lymphocytes were estimated with the Kaplan-Meier (K-M) method. Support vector machine (SVM) methods were used to develop a prognostic classifier for breast cancer. Results: A total of 190 patients were enrolled. Patients with low level of cluster of differentiation (CD)3+ lymphocytes had worse DFS and OS (P Conclusions: Patients with low level of CD3+ lymphocytes could have a poorer survival and the SVM method could predict prognosis in breast cancer patients.

Purpose Breast cancer is the most common cancer among women. Pemetrexed, a new generation antifolate drug, is one of the primary treatments for breast cancer. However, multidrug resistance (MDR) in breast cancer greatly hampers the therapeutic efficacy of chemotherapies such as pemetrexed. Nanomedicine is emerging as a promising alternative technique to overcome cancer MDR. Thus, pemetrexed-loaded d-alpha tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) liposomes (liposomal pemetrexed) were developed as a strategy to overcome MDR to pemetrexed in breast cancer. Materials and methods Liposomal pemetrexed was developed using the calcium acetate gradient method. The cytotoxic effects, apoptosis-inducing activity, in vivo distribution, and antitumor activity of liposomal pemetrexed were investigated. Results Liposomal pemetrexed was small in size (160.77 nm), with a small polydispersity of <0.1. The encapsulation efficacy of liposomal pemetrexed was 63.5%, which is rather high for water-soluble drugs in liposomes. The IC50 of liposomal pemetrexed following treatment with MDR breast cancer cells (MCF-7 cells overexpressing ABCC5) was 2.6-fold more effective than pemetrexed. The in vivo biodistribution study showed that the liposomes significantly accumulated in tumors 24 h after injection. The antitumor assay in mice bearing MDR breast cancer xenograft tumors confirmed the superior antitumor activity of liposomal pemetrexed over pemetrexed. It was also found that the improved therapeutic effect of liposomal pemetrexed may be attributed to apoptosis through both extrinsic and intrinsic pathways. Conclusion Liposomal pemetrexed represents a potential therapeutic approach for overcoming breast cancer MDR.

低度恶性肌纤维母细胞肉瘤(low-grade myofibroblastic sarcoma,LGMS)是一种罕见的恶性肿瘤.上海交通大学医学院附属新华医院普外科收治1例源自乳腺的LGMS,笔者复习相关文献,探讨其临床病理学特点、诊断及鉴别诊断要点,以进一步提高医务工作者对该病的认识. 一、临床资料 患者,女,47岁,因"发现左乳肿块半年并逐渐增大"至外院检查,乳腺超声发现:左乳外侧3点钟方向见一低回声团,边界可见,大小约3.8 cm×2.1 cm,团块内见1.0 cm×0.6 cm无回声,团块内部及周边未探及彩色血流信号.于2016年 2月在全身麻醉下行乳房肿块切除术.

PURPOSE:To investigate the effects of trastuzumab (herceptin) and fulvestrant (falsodex) either in combination or alone, on downstream cell signaling pathways in lab-cultured human HR+/HER2+ breast cancer cell lines ZR-75-1 and BT-474, as well as on protein expression levels in mouse xenograft tissue. METHODS:Cells were cultivated in the presence of trastuzumab or fulvestrant or both. Molecular events that resulted in an inhibition of cell proliferation and cell cycle progression or in an increased rate of apoptosis were studied. The distribution and abundance of the proteins p-Akt and p-Erk expressed in these cells in response to single agents or combinatorial treatment were also investigated. In addition, the effects of trastuzumab and fulvestrant, either as single agents or in combination on tumor growth as well as on expression of the protein p-MED1 expressed in in vivo mouse xenograft models was also examined. RESULTS:Cell proliferation was increasingly inhibited by trastuzumab or fulvestrant or both, with a CI<1 and DRI>1 in both human cell lines. The rate of apoptosis increased only in the BT-474 cell line and not in the ZR-75-1 cell line upon treatment with fulvestrant and not trastuzumab as a single agent (P<0.05). Interestingly, fulvestrant, in combination with trastuzumab, did not significantly alter the rate of apoptosis (in comparison with fulvestrant alone), in the BT-474 cell line (P>0.05). Cell accumulation in the G1 phase of cell cycle was investigated in all treatment groups (P<0.05), and the combination of trastuzumab and fulvestrant reversed the effects of fulvestrant alone on p-Akt and p-Erk protein expression levels. Using ZR-75-1 or BT-474 to generate in vivo tumor xenografts in BALB/c athymic mouse models, we showed that a combination of both drugs resulted in a stronger inhibition of tumor growth (P<0.05) and a greater decrease in the levels of activated MED1 (p-MED1) expressed in tumor issues compared with the use of either drug as a single agent. CONCLUSIONS:We demonstrate that the administration of trastuzumab and fulvestrant in combination results in positive synergistic effects on both, ZR-75-1 and BT-474 cell lines. This combinatorial approach is likely to reduce physiological side effects of both drugs, thus providing a theoretical basis for the use of such combination treatment in order to resolve HR+/HER2+ triple positive breast cancer that has previously been shown to be resistant to endocrine treatment alone.