Res-TransNet: A Hybrid deep Learning Network for Predicting Pathological Subtypes of lung Adenocarcinoma in CT Images.

This study aims to develop a CT-based hybrid deep learning network to predict pathological subtypes of early-stage lung adenocarcinoma by integrating residual network (ResNet) with Vision Transformer (ViT). A total of 1411 pathologically confirmed ground-glass nodules (GGNs) retrospectively collected from two centers were used as internal and external validation sets for model development. 3D ResNet and ViT were applied to investigate two deep learning frameworks to classify three subtypes of lung adenocarcinoma namely invasive adenocarcinoma (IAC), minimally invasive adenocarcinoma and adenocarcinoma in situ, respectively. To further improve the model performance, four Res-TransNet based models were proposed by integrating ResNet and ViT with different ensemble learning strategies. Two classification tasks involving predicting IAC from Non-IAC (Task1) and classifying three subtypes (Task2) were designed and conducted in this study. For Task 1, the optimal Res-TransNet model yielded area under the receiver operating characteristic curve (AUC) values of 0.986 and 0.933 on internal and external validation sets, which were significantly higher than that of ResNet and ViT models (p < 0.05). For Task 2, the optimal fusion model generated the accuracy and weighted F1 score of 68.3% and 66.1% on the external validation set. The experimental results demonstrate that Res-TransNet can significantly increase the classification performance compared with the two basic models and have the potential to assist radiologists in precision diagnosis.

Association between serum chloride levels and estimated glomerular filtration rate among US adults: evidence from NHANES 1999-2018.

PURPOSE: Chloride, the predominant anion in extracellular fluid from humans, is essential to maintaining homeostasis. One important metric for thoroughly assessing kidney function is the estimated glomerular filtration rate (eGFR). However, the relationship between variations in serum chloride concentration and eGFR in general populations has been poorly studied. Therefore, the purpose of this study is to elucidate the correlation between serum chloride levels and eGFR within the United States' adult population. METHODS: This cohort study was conducted using data from the National Health and Nutrition Examination Survey (NHANES), which covered the years 1999-2018. We employed multiple linear regression analysis and subgroup analysis to evaluate the correlation between serum chloride concentration and eGFR. To examine the nonlinear association between serum chloride levels and eGFR, restricted cubic spline analyses were employed. RESULTS: Data from 49,008 participants in this cohort study were used for the chloride analysis. In the comprehensively adjusted model, a noteworthy inverse relationship was discovered between chloride plasma concentration and eGFR. Restricted cubic spline analyses revealed a significant nonlinear relationship between chloride levels and eGFR (P for overall < 0.001 and P for nonlinear < 0.001). A significant interaction was observed between eGFR and plasma chloride concentration (all P < 0.001 for interaction) among the subgroups characterized by sex, household income to poverty ratio, BMI, hypertension, and diabetes. CONCLUSION: Our findings suggest that higher levels of chloride plasma concentration were linked to decreased eGFR. These findings underscore the significance of monitoring chloride plasma concentration as a potential indicator for identifying individuals at risk of developing chronic kidney disease (CKD).

Molecular-subtype guided automatic invasive breast cancer grading using dynamic contrast-enhanced MRI.

BACKGROUND AND OBJECTIVES: Histological grade and molecular subtype have presented valuable references in assigning personalized or precision medicine as the significant prognostic indicators representing biological behaviors of invasive breast cancer (IBC). To evaluate a two-stage deep learning framework for IBC grading that incorporates with molecular-subtype (MS) information using DCE-MRI. METHODS: In Stage I, an innovative neural network called IOS2-DA is developed, which includes a dense atrous-spatial pyramid pooling block with a pooling layer (DA) and inception-octconved blocks with double kernel squeeze-and-excitations (IOS2). This method focuses on the imaging manifestation of IBC grades and performs preliminary prediction using a novel class F1-score loss function. In Stage II, a MS attention branch is introduced to fine-tune the integrated deep vectors from IOS2-DA via Kullback-Leibler divergence. The MS-guided information is weighted with preliminary results to obtain classification values, which are analyzed by ensemble learning for tumor grade prediction on three MRI post-contrast series. Objective assessment is quantitatively evaluated by receiver operating characteristic curve analysis. DeLong test is applied to measure statistical significance (P < 0.05). RESULTS: The molecular-subtype guided IOS2-DA performs significantly better than the single IOS2-DA in terms of accuracy (0.927), precision (0.942), AUC (0.927, 95% CI: [0.908, 0.946]), and F1-score (0.930). The gradient-weighted class activation maps show that the feature representations extracted from IOS2-DA are consistent with tumor areas. CONCLUSIONS: IOS2-DA elucidates its potential in non-invasive tumor grade prediction. With respect to the correlation between MS and histological grade, it exhibits remarkable clinical prospects in the application of relevant clinical biomarkers to enhance the diagnostic effectiveness of IBC grading. Therefore, DCE-MRI tends to be a feasible imaging modality for the thorough preoperative assessment of breast biological behavior and carcinoma prognosis.

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition).

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.

MicroRNA-216b targets HK2 to potentiate autophagy and apoptosis of breast cancer cells via the mTOR signaling pathway.

Patients suffering from breast cancer (BC) still have a poor response to treatments, even though early detection and improved therapy have contributed to a reduced mortality. Recent studies have been inspired on the association between microRNAs (miRs) and therapies of BC. The current study set out to investigate the role of miR-216b in BC, and further analyze the underlining mechanism. Firstly, hexokinase 2 (HK2) and miR-216b were characterized in BC tissues and cells by RT-qPCR and Western blot assay. In addition, the interaction between HK2 and miR-216b was analyzed using dual luciferase reporter assay. BC cells were further transfected with a series of miR-126b mimic or inhibitor, or siRNA targeting HK2, so as to analyze the regulatory mechanism of miR-216b, HK2 and mammalian target of rapamycin (mTOR) signaling pathway, and to further explore their regulation in BC cellular behaviors. The results demonstrated that HK2 was highly expressed and miR-216b was poorly expressed in BC cells and tissues. HK2 was also verified as a target of miR-216b with online databases and dual luciferase reporter assay. Functionally, miR-216b was found to be closely associated with BC progression via inactivating mTOR signaling pathway by targeting HK2. Moreover, cell viability, migration and invasion were reduced as a result of miR-216b upregulation or HK2 silencing, while autophagy, cell cycle arrest and apoptosis were induced. Taken together, our findings indicated that miR-216 down-regulates HK2 to inactivate the mTOR signaling pathway, thus inhibiting the progression of BC. Hence, this study highlighted a novel target for BC treatment.

miR-613 Suppresses Chemoresistance and Stemness in Triple-Negative Breast Cancer by Targeting FAM83A.

INTRODUCTION: Triple-negative breast cancer (TNBC) is the most aggressive malignancy of breast cancer, which represents about 20% of all cases. The prognosis of TNBC remains unfavorable due to the lack of targeted therapy and chemoresistance. The aim of this study is to investigate the role of miR-613 in TNBC. MATERIAL AND METHODS: Quantitative RT-PCT was used to explore the expression of miR-613 in breast cancer clinical samples and cell lines. MTT, colony formation assay, spheroid formation assay and xenograft tumor growth assay were used to investigate the role of miR-613 in vitro and in vivo. Cell apoptosis and surface marker expression were measured by flow cytometry. Dual-luciferase reporter assay was used to explore the function of miR-613 in regulating FAM83A 3'UTR. Immunohistochemical staining was used to investigate the expression of FAM83A in TNBC tissues. RESULTS: We found that miR-613 expression was significantly downregulated in breast cancer tissues and was even lower in TNBC compared with that in other types of breast cancer. A similar result was found in breast cancer cell lines. Further analysis indicated that miR-613 could suppress TNBC cell growth, chemoresistance and stem-cell-like phenotype. Moreover, we also demonstrated that miR-613 suppressed tumorigenesis in vivo. Mechanically, we explored the downstream target of miR-613 and identified that miR-613 could directly bind to the 3'UTR of FAM83A, which contributed to the miR-613 mediated tumor suppression. The expression of miR-613 and FAM83A was negatively correlated. Restoring the expression of FAM83A attributed to the chemoresistance and stemness of TNBC cells. CONCLUSION: We demonstrated that loss of miR-613 was critical for TNBC malignancy and restoring its expression could be served as a potential approach for TNBC treatment.

T-distribution stochastic neighbor embedding for fine brain functional parcellation on rs-fMRI.

In human functional connectome and network analyses, brain subregions that are functionally parcellated have a better consistency than do anatomical subregions. Resting-state functional magnetic resonance imaging (rs-fMRI) signals can function as coherent connectivity patterns that can be used to assess human brain functional architecture. In this paper, an optimized framework that combines automatic spectral clustering with dimensionality reduction is presented for fine-grained functional parcellation of rs-fMRI of the human brain. First, the t-distribution stochastic neighborhood embedding (t-SNE) algorithm extracts features from the high-dimensional functional connectivity patterns between voxels of the brain regions to be segmented and the whole brain. Then, the number of clusters is determined, and each voxel in the regions is parcellated by the automatic spectral clustering algorithm based on the eigengap. A quantitative validation of the proposed methodology in synthetic seed regions demonstrated its accuracy and performance superiority compared to previous methods. Moreover, we were able to successfully divide the parahippocampal gyrus into three subregions in both the left and right hemispheres. The distinctive functional connectivity patterns of these subregions, educed from rs-fMRI data, further established the validity of the parcellation results. Notably, our findings reveal a novel insight into brain functional parcellation as well as the construction of functional atlases for future Cognitive Connectome analyses.

Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA-328-3p-mediated inhibition of COL1A1.

Circular RNAs (circRNAs) are a group of non-coding RNAs implicated in the pathogenesis of cancer progression, which exert their functions via regulation of microRNAs (miRNAs) and genes. The present study uses gain- and loss-of-function approaches to evaluate the functions of hsa_circRNA_002178 in angiogenesis along with energy metabolism and underlying downstream signals. The expression pattern of hsa_circRNA_002178 in clinical breast cancer tissues and its association with prognosis were characterized at first. Next, the energy metabolism and angiogenesis as well as cell viability were evaluated when the expression of hsa_circRNA_002178 in breast cancer cells was knocked down by siRNA. The interaction between hsa_circRNA_002178 and its downstream miR-328-3p was identified, followed by the analysis of their functions in regulation of breast cancer cellular behaviours. The target gene of miR-328-3p was predicted and verified, followed by identifying its role in the breast cancer progression. Higher expression of hsa_circRNA_002178 shared an association with worse prognosis in breast cancer. The inhibition of hsa_circRNA_002178 resulted in reductions in cell viability, energy metabolism and tube formation ability. Hsa_circRNA_002178 could competitively bind to miR-328-3p and down-regulated its expression. Restoration of miR-328-3p eliminated the tumour-promoting effects of hsa_circRNA_002178. COL1A1, as a target of miR-328-3p, could be up-regulated by overexpression of hsa_circRNA_002178. In vivo experiments further confirmed the inhibition of tumour growth and inflammation by silencing hsa_circRNA_002178 or up-regulating miR-328-3p. Taken together, hsa_circRNA_002178 is highlighted as a promising target for breast cancer due to the anti-tumour effects achieved by silencing hsa_circRNA_002178.

Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1.

BACKGROUND: Breast cancer is the most common malignancy in women. Triple-negative breast cancer (TNBC) refers to a special subtype that is deficient in the expression of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2). In this study, a variety of bioinformatics analysis tools were used to screen Hub genes related to the occurrence and development of triple negative breast cancer, and their biological functions were analyzed. METHODS: Gene Expression Omnibus (GEO) breast cancer microarray data GSE62931 was selected as the research object. The differentially expressed genes (DEGs) were screened and the protein-protein interaction (PPI) network of DEGs was constructed using bioinformatics tools. The Hub genes were also screened. The Gene Ontology (GO) knowledgebase and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for biological enrichment analysis. The Gene Expression Profiling Interactive Analysis (GEPIA) online tool was used to verify the expression of the screened genes and patient survival. The effects of polo-like kinase 1 (PLK1) on the proliferation, invasion, migration, and dryness of breast cancer cells were verified using cell counting kit 8 (CCK-8), transwell migration assays, scratch tests, and clone formation tests. An animal model of subcutaneous xenotransplantation of breast cancer was established to evaluate the effect of PLK1 on the proliferation of breast cancer. RESULTS: A total of 824 DEGs were screened by GSE62931 microarray data; 405 of which were up-regulated and 419 of which were down-regulated. Functional enrichment analysis showed that these DEGs were mainly enriched in cancer-related pathways and were primarily involved in biological processes (BP) such as cell and mitotic division. From the Hub gene screening, PLK1 was further identified as the Hub gene associated with TNBC. Cell and animal experiments indicated that PLK1 promotes the proliferation, invasion, migration, and clone formation of breast cancer cells. CONCLUSIONS: Gene chip combined with bioinformatics methods can effectively analyze the DEGs related to the occurrence and development of breast cancer, and the screening of PLK1 can provide theoretical guidance for further research on the molecular mechanism of breast cancer and the screening of molecular markers.

Dual-functional neural network for bilateral hippocampi segmentation and diagnosis of Alzheimer's disease.

PURPOSE: Knowing the course of Alzheimer's disease is very important to prevent the deterioration of the disease, and accurate segmentation of sensitive lesions can provide a visual basis for the diagnosis results. This study proposes an improved end-to-end dual-functional 3D convolutional neural network for segmenting bilateral hippocampi from 3D brain MRI scans and diagnosing AD progression states simultaneously. METHODS: The proposed neural network is based on the V-Net and adopts an end-to-end structure. In order to relieve the excessive amount of convolutional parameters at the bottom of the V-Net, we change them to bottleneck architecture. Based on the segmentation network, we establish a classification network for diagnosing pathological states of brain. In order to balance the two tasks of hippocampi segmentation and brain pathological states diagnosis, we designed a unique loss function. This study included 132 samples, of which 100 were selected as training, and the remaining 32 were used to test the performance of our model. During training, we adopted fivefold cross-validation method. RESULTS: We selected the intersection over union and dice coefficient to evaluate the hippocampus segmentation performance, while the brain pathological states diagnosis performance was evaluated by accuracy, specificity, sensitivity, precision and F1 score. By using the proposed neural network, the left hippocampi segmentation Iou and dice coefficient reach 0.8240 ± 0.020 and 0.9035 ± 0.020, respectively. The right hippocampi Iou and dice coefficient reach 0.8454 ± 0.023 and 0.9162 ± 0.023, respectively. The accuracy, specificity, sensitivity, precision and F1 score of three-category classification of brain pathology are 84%, 92%, 84%, 86% and 85%, respectively. CONCLUSION: The proposed neural network has two functions of brain pathological states diagnosis and bilateral hippocampi segmentation with higher robustness and accuracy, respectively. The segmented bilateral hippocampi can be used as a reference for clinical decision making or intervention.

Studies on anti-hepatocarcinoma effect, pharmacokinetics and tissue distribution of carboxymethyl chitosan based norcantharidin conjugates.

Aiming to enhance therapeutic efficiency and reduce toxic effect of norcantharidin (NCTD), NCTD-conjugated carboxymethyl chitosan (CMCS) conjugates (CNC) were prepared and evaluated for the treatment of hepatocellular carcinoma. In vitro cellular assays revealed that CNC conjugates possessed potent inhibitory effects on the proliferation and migration of BEL-7402 cells. Besides, CNC could change nuclear morphology of tumor cells. In comparison with free NCTD at equivalent dose, CNC exerted enhanced therapeutic efficiency and diminished systemic toxicity in H22 tumor-bearing mice with a tumor inhibition rate of 56.20%. Further investigation about pharmacokinetics and tissue distribution by high performance liquid chromatography (HPLC) analysis indicated that CNC showed a longer retention time in blood circulation and reduced distribution in heart and kidney tissues, thereby exerting different antitumor efficacy and toxicity compared with free NCTD. Our results suggested that CNC conjugates based on CMCS as polymer carriers might be used as a potential clinical alternative for NCTD in tumor therapy.

Improved synergetic therapy efficiency of cryoablation and nanoparticles for MCF-7 breast cancer.

AIM: Current cryoablation therapy easily induces a high tumor recurrence, it is therefore necessary to develop an effective method to enhance its antitumor efficacy. MATERIALS & METHODS: We solve the aforementioned problem by introducing doxorubicin (DOX) loading methoxy polyethylene glycol-polylactic-co-glycolic acid-poly-L-lysine-cyclic arginine-glycine-aspartic acid peptide nanoparticles (DOX nanoparticles) in the process of cryoablation. RESULTS: The combination of cryoablation and DOX nanoparticles greatly decreases the recurrence rate of breast cancer, which is owing to the specific targeting therapy of DOX nanoparticles for residuary breast cancer cells after cryoablation. Therefore, the survival time of MCF-7 breast cancer bearing mice significantly increases. CONCLUSION: The synergetic therapy of cryoablation and DOX nanoparticles is an effective therapy means for breast cancer. This strategy provides new means for treating breast cancer.

Triple cell-responsive nanogels for delivery of drug into cancer cells.

In this report, biocompatible nanogels with multi cell-responsiveness (thermo-, pH- and reduction) were fabricated by in situ cross-linking of alginate (AG) using cystamine (Cys) as a cross-linker through an emulsion approach, in the presence of a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM). The AG/PNIPAM nanogels exhibited an abrupt swelling upon temperature increase from 37 to 25 °C under physiological conditions (497 ±â€¯258 nm at 29 °C and 147 ±â€¯48 nm at 37 °C). The nanogels were easily taken up by cancer cells at high temperature, where temperature variation could induce toxicity against cancer cells. Furthermore, the accelerated release under reducible and acidic microenvironments inside cells, together their thermosensitivity, made the nanogels selectively deliver drug intracellulary to exert a synergistical anticancer efficacy, potentiating therir high promise for drug delivery application.

Drug-mediation formation of nanohybrids for sequential therapeutic delivery in cancer cells.

In order to overcome the multidrug resistance (MDR) of tumor cells, it is very important to develop nanocarriers which can effectively load drugs while releasing them in a sequential way. Herein, nanohybrids with such properties have been fabricated by a first loading of one anticancer drug onto a silicate nanodisk (Laponite (LP), 25 nm in diameter and 0.92 nm in thickness) and a subsequent assembly with a pH sensitive poly(N-vinylpyrrolidone) (PVP) as a protective layer, followed by a loading of with another anticancer drug. The resulting nanohybrids (LDPM) present a high drug encapsulation efficiency and long-term colloidal stability. However, if the two drugs are loaded onto LP before PVP decoration, the formed particles tend to form microsized aggregates with poor colloidal stability. In vitro release study indicates that LDPM can deliver the anticancer drugs in a sequential way, which can be further accelerated under acidic microenvironments mimicking both solid tumor and endo-lysosomal compartments, exerting synergistic anticancer cytotoxicity. The drug-mediated formation of nanocarriers may enlighten a design of novel nanoplatform for co-delivery of therapeutic agents, beyond anticancer drugs, in a combinative way for drug delivery applications.

Negative effect of nanoconfinement on water transport across nanotube membranes.

Nanoconfinement environments are commonly considered advantageous for ultrafast water flow across nanotube membranes. This study illustrates that nanoconfinement has a negative effect on water transport across nanotube membranes based on molecular dynamics simulations. Although water viscosity and the friction coefficient evidently decrease because of nanoconfinement, water molecular flux and flow velocity across carbon nanotubes decrease sharply with the pore size of nanotubes. The enhancement of water flow across nanotubes induced by the decreased friction coefficient and water viscosity is markedly less prominent than the negative effect induced by the increased flow barrier as the nanotube size decreases. The decrease in water flow velocity with the pore size of nanotubes indicates that nanoconfinement is not essential for the ultrafast flow phenomenon. In addition, the relationship between flow velocity and water viscosity at different temperatures is investigated at different temperatures. The results indicate that flow velocity is inversely proportional to viscosity for nanotubes with a pore diameter above 1 nm, thereby indicating that viscosity is still an effective parameter for describing the effect of temperature on the fluid transport at the nanoscale.

Targeting long non-coding RNA DANCR inhibits triple negative breast cancer progression.

Triple negative breast cancer (TNBC) is non-responsive to conventional anti-hormonal and Her2-targeted therapies, making it necessary to identify new molecular targets for therapy. Long non-coding RNA anti-differentiation ncRNA (lncRNA DANCR) was identified participating in carcinogenesis of hepatocellular carcinoma, but its expression and potential role in TNBC progression is still unclear. In the present study, our results showed that DANCR expression was increased in TNBC tissues compared with the adjacent normal tissues using quantitative real-time PCR (qRT-PCR) in 63 TNBC specimens. Patients with higher DANCR expression correlated with worse TNM stages as well as a shorter overall survival (OS) using Kaplan-Meier analysis. When the endogenous DANCR was knocked-down via specific siRNA, cell proliferation and invasion were decreased obviously in the MDA-MB-231 cells. In vivo xenograft experiments showed that knockdown of the DANCR in MDA-MB-231 cells reduced the tumor growth significantly. Furthermore, a compendium of TNBC cancer stem cell markers such as CD44, ABCG2 transporter and aldehyde dehydrogenase (ALDH1) were greatly downregulated in the MDA-MB-231 cells with DANCR knockdown. Molecular mechanistic studies revealed that knockdown of DANCR was associated with increased binding of EZH2 on the promoters of CD44 and ABCG2, and concomitant reduction of expression of these genes suggested that they may be DANCR targets in TNBC. Thus, our study demonstrated that targeting DANCR expression might be a viable therapeutic approach to treat triple negative breast cancer.

Folate receptor-targeted ultrasonic PFOB nanoparticles: Synthesis, characterization and application in tumor-targeted imaging.

In this study, we aimed to determine an effective strategy for the synthesis of folate receptor (FR) targeted-nanoparticles (FRNPs). The nanoparticles used as ultrasound contrast agents (UCAs) were composed of a liquid core of perfluorooctyl bromide (PFOB) liposome and a targeted shell chemically conjugated with folic acid (FA) and polyethylene glycol (PEG). This was done in order to avoid recognition and clearance by the mononuclear phagocyte system [also known as the reticuloendothelial system (RES)] and enhance the targeting capability of the nanoparticles to tumors overexpressing folate receptor (FR). The FRNPs exhibited an average particle size of 301±10.8 nm and surface potential of 39.1±0.43 mV. Subsequently, in vitro, FRNPs labeled with FITC fluorescence dye were visibly uptaken into the cytoplasm of FR-overexpressing cancer cells (Bel7402 and SW620 cells), whereas the A549 cells expressing relatively low levels of FR just bound with few FRNPs. These results demonstrated that FRNPs have a high affinity to FR-overexpressing cancer cells. Additionally, in in vivo experiments, FRNPs achieved a greater enhancement of tumor ultrasound imaging and a longer enhancement time in FR-overexpressing tumors and the Cy7-labeled FRNPs exhibited a relatively high tumor-targeted distribution in FR­overexpressing tumors. Targeted ultrasound and fluorescence imaging revealed that FRNPs have the ability to target FR-overexpressing tumors and ex vivo fluorescence imaging was then used to further verify and confirm the presence of FRNPs in tumor tissues with histological analysis of the tumor slices. On the whole, our data demonstrate that the FRNPs may prove to be a promising candidate for the early diagnosis for FR-overexpressing tumors at the molecular and cellular levels.

Periareolar incision for the management of benign breast tumors.

Benign breast tumors (BBTs) are common in women. The traditional surgical resection method for the various types of BBT leaves obvious scars and affects the appearance of the breast. The present study introduces the experience of a single institution in the treatment of BBT by periareolar incision. The clinical data of 153 patients (182 breasts) with BBT who had undergone a resection via a periareolar incision between January 2010 and December 2012 in Qilu Hospital, Shandong University (Jinan, Shandong, China), was retrospectively analyzed. All incisions were primary healing. Of the 153 patients, 1 (0.7%) developed a hematoma and 2 (1.3%) developed slight nipple ischemia. No infections or other complications were observed. During 1 month to 3 years of follow-up, the cosmetic effects were assessed. Periareolar incision is not only suitable for all types of breast surgery for benign tumor resection, but also has the advantage of a hidden incision, a small scar, no ischemic necrosis of the nipple areola, high patient satisfaction and good post-operative cosmetic effect. The technique is therefore a good surgical incision choice that is worthy of note.

Preparation and Characterization of Novel Perfluorooctyl Bromide Nanoparticle as Ultrasound Contrast Agent via Layer-by-Layer Self-Assembly for Folate-Receptor-Mediated Tumor Imaging.

A folate-polyethylene glycol-chitosan derivative was synthesized and its structure was characterized. An optimal perfluorooctyl bromide nanocore template was obtained via utilizing the ultrasonic emulsification method combining with orthogonal design. The targeted nanoparticles containing targeted shell of folate-polyethylene glycol-chitosan derivative and perfluorooctyl bromide nanocore template of ultrasound imaging were prepared successfully by exploiting layer-by-layer self-assembly as contrast agent for ultrasound. Properties of the novel perfluorooctyl bromide nanoparticle were extensively studied by Dynamic Light Scattering and Transmission Electron Microscopy. The targeted nanoparticle diameter, polydispersity, and zeta potential are around 229.5 nm, 0.205, and 44.7 ± 0.6 mV, respectively. The study revealed that spherical core-shell morphology was preserved. Excellent stability of targeted nanoparticle is evidenced by two weeks of room temperature stability tests. The results of the cell viability assay and the hemolysis test confirmed that the targeted nanoparticle has an excellent biocompatibility for using in cell studies and ultrasound imaging in vivo. Most importantly, in vitro cell experiments demonstrated that an increased amount of targeted nanoparticles was accumulated in hepatocellular carcinoma cell line Bel7402 relative to hepatoma cell line L02. And targeted nanoparticles had also shown better ultrasound imaging abilities in vitro. The data suggest that the novel targeted nanoparticle may be applicable to ultrasonic molecular imaging of folate-receptor overexpressed tumor.