Gas-induced controllable synthesis of the Cu(100) crystal facet for the selective electroreduction of CO2 to multicarbon products.

Electrocatalytic CO2 reduction (ECR) to high value-added chemicals is an excellent method to attenuate the impact of greenhouse effect caused by CO2. At the same time, multicarbon products (C2+) get extensive attention in view of their relatively high energy density and market price. At present, Cu is an important metal electrocatalyst to convert CO2 into multicarbon products (e.g. ethylene, ethanol, and n-propanol); however, its poor selectivity impedes its practical application. It is well-known that the Cu(100) crystal facet can enhance the selectivity toward multicarbon products among different Cu crystal facets. Herein, the Cu nanoparticles were firstly prepared using the inductive effect of different gases (CO2, CO, Ar, N2, and air) during the Cu electrodeposition processes, in which the CO2-induced Cu catalyst (Cu-CO2) showed the largest normalized content of the Cu(100) crystal facet and the highest C2+ faradaic efficiency of 69% at a current density of 80 mA cm-2 in ECR. Subsequently, the different CO2 pressures during the Cu electrodepositions were studied to reveal the optimal CO2 pressure in the CO2-induced Cu synthesis for improved Cu(100) content as well as C2+ faradaic efficiency. Finally, density functional theory (DFT) calculations confirmed that CO2 molecules preferred to get adsorbed on the Cu(100) crystal facet, which resulted in not only the presence of dominant Cu(100) during the CO2-induced Cu synthesis but also the good electrocatalytic performance in ECR.

Combination of Breast Ultrasound With Magnetic Resonance Imaging in the Diagnosis of Non-mass-like Breast Lesions Detected on Ultrasound: A New Integrated Strategy to Improve Diagnostic Performance.

OBJECTIVE: The aim of the work described here was to evaluate the diagnostic performance of a new integrated strategy using breast ultrasound (US) combined with magnetic resonance imaging (MRI) to differentiate benign and malignant breast non-mass-like lesions (NMLs) detected on US. METHODS: From October 2017 to January 2021, 183 NMLs detected on US that had undergone MRI examinations were included in this respective study. Pathological results were used as the reference standard. The integrated diagnostic strategy of breast US combined with MRI based on a combination of MRI Breast Imaging Reporting and Data System (BI-RADS) with discriminant sonographic indicators highly associated with malignancy was established and validated in a cohort of 61 women. The diagnostic performances of US, MRI and the combined method were calculated and compared. RESULTS: In the training set, the area under the receiver operating characteristic curve (AUC), sensitivity and specificity of US, MRI and the integrated diagnostic strategy using US combined with MRI for NMLs were 0.730, 93.7% and 52.3%; 0.849, 94.7% and 75.0%; and 0.901, 92.6% and 87.5%, respectively. Compared with US or MRI alone, the integrated diagnostic strategy significantly increased the AUC (p < 0.001, p = 0.007) and specificity (p < 0.001, p = 0.034) while maintaining high sensitivity (p = 0.774, p = 0.551). In the validation set, the integrated strategy of US combined with MRI (AUC = 0.899) also had good performance compared with US (AUC = 0.728) or MRI (AUC = 0.838). CONCLUSION: The integrated diagnostic strategy of US combined with MRI exhibited good performance for breast NMLs compared with either modality used alone, which can improve the diagnostic specificity while maintaining high sensitivity.

Novel urine cell-free DNA methylation markers for hepatocellular carcinoma.

An optimized hepatocellular carcinoma (HCC)-targeted methylation next generation sequencing assay was developed to discover HCC-associated methylation markers directly from urine for HCC screening. Urine cell-free DNA (ucfDNA) isolated from a discovery cohort of 31 non-HCC and 30 HCC was used for biomarker discovery, identifying 29 genes with differentially methylated regions (DMRs). Methylation-specific qPCR (MSqPCR) assays were developed to verify the selected DMRs corresponding to 8 genes (GRASP, CCND2, HOXA9, BMP4, VIM, EMX1, SFRP1, and ECE). Using archived ucfDNA, methylation of GRASP, HOXA9, BMP4, and ECE1, were found to be significantly different (p < 0.05) between HCC and non-HCC patients. The four markers together with previously reported GSTP1 and RASSF1A markers were assessed as a 6-marker panel in an independent training cohort of 87 non-HCC and 78 HCC using logistic regression modeling. AUROC of 0.908 (95% CI, 0.8656-0.9252) was identified for the 6-marker panel with AFP, which was significantly higher than AFP-alone (AUROC 0.841 (95% CI, 0.778-0.904), p = 0.0026). Applying backward selection method, a 4-marker panel was found to exhibit similar performance to the 6-marker panel with AFP having 80% sensitivity compared to 29.5% by AFP-alone at a specificity of 85%. This study supports the potential use of methylated transrenal ucfDNA for HCC screening.

Impact of Cell-Debris and Room-Temperature Storage on Urine Circulating Tumor DNA from Hepatocellular Carcinoma.

This study evaluated the impact of cell debris and 7-day room temperature storage on the quality and yield of transrenal DNA. Archived urine specimens collected from five hepatocellular carcinoma (HCC) patients and two pregnant women carrying male fetuses were used to assess the impact of cell debris on urine cell-free DNA (ucfDNA) isolation as measured by quantitative PCR for Y-chromosome DNA, or HCC-associated mutation and methylation markers, and by capillary electrophoresis. Prospectively collected urine from 21 HCC patients was aliquoted after collection for paired immediate freezing versus 7-day room temperature storage followed by freezing for further analysis. Cell debris contained more Y-chromosome DNA than supernatant in three of the six urine specimens tested from pregnant women, suggesting that cell debris can be associated with 20.6% to 84.9% of transrenal ucfDNA. Ninety-five percent (20 of 21) of frozen and room temperature urine pairs had overlapping DNA size distribution. ucfDNA quantity determined by quantitative PCR for TP53, CTNNB1, TERT, and HCC-associated urine circulating tumor DNA markers were statistically similar between room temperature and frozen samples. This suggests no significant difference in DNA degradation between the groups. The association of transrenal ucfDNA with cell debris and HCC circulating DNA stability at room temperature is significant to further the understanding of transrenal circulating tumor DNA pre-analytical handling for HCC screening.

Purification of Circulating Tumor Cells Based on Multiantibody-Modified Magnetic Nanoparticles and Molecular Analysis toward Epithelial Ovarian Cancer Detection.

Circulating tumor cells (CTCs) are valuable circulating biomarkers of cancer, which carry primary tumor information and may provide real-time assessment of tumor status as well as treatment response in cancer patients. Herein, we developed a novel assay for accurate diagnosis and dynamic monitoring of epithelial ovarian cancer (EOC) using CTC RNA analysis. Multiantibody-modified magnetic nanoparticles were prepared for purification of EOC CTCs from whole blood samples of clinical patients. Subsequently, nine EOC-specific mRNAs of purified CTCs were quantified using droplet digital PCR. The EOC CTC Score was generated using a multivariate logistic regression model for each sample based on the transcripts of the nine genes. This assay exhibited a distinguishing diagnostic performance for the detection of EOC (n = 17) from benign ovarian tumors (n = 30), with an area under the receiver operating characteristic curve (AUC) of 0.96 (95% CI = 0.91-1.00). Moreover, dynamic changes of the EOC CTC Score were observed in patients undergoing treatment, demonstrating the potential of the assay for monitoring EOC. In conclusion, we present an accurate assay for the diagnosis and monitoring of EOC via CTC RNA analysis, and the results suggest that it may provide a promising solution for the detection and treatment response assessment of EOC.

New Perspectives on Chinese Medicine in Treating Hepatic Fibrosis: Lipid Droplets in Hepatic Stellate Cells.

Hepatic fibrosis (HF) is a wound healing response featuring excessive deposition of the extracellular matrix (ECM) and activation of hepatic stellate cells (HSCs) that occurs during chronic liver injury. As an initial stage of various liver diseases, HF is a reversible pathological process that, if left unchecked, can escalate into cirrhosis, liver failure, and liver cancer. HF is a life-threatening disease presenting morbidity and mortality challenges to healthcare systems worldwide. There is no specific and effective anti-HF therapy, and the toxic side effects of the available drugs also impose a heavy financial burden on patients. Therefore, it is significant to study the pathogenesis of HF and explore effective prevention and treatment measures. Formerly called adipocytes, or fat storage cells, HSCs regulate liver growth, immunity, and inflammation, as well as energy and nutrient homeostasis. HSCs in a quiescent state do not proliferate and store abundant lipid droplets (LDs). Catabolism of LDs is characteristic of the activation of HSCs and morphological transdifferentiation of cells into contractile and proliferative myofibroblasts, resulting in the deposition of ECM and the development of HF. Recent studies have revealed that various Chinese medicines (e.g., Artemisia annua, turmeric, Scutellaria baicalensis Georgi, etc.) are able to effectively reduce the degradation of LDs in HSCs. Therefore, this study takes the modification of LDs in HSCs as an entry point to elaborate on the process of Chinese medicine intervening in the loss of LDs in HSCs and the mechanism of action for the treatment of HF.

Dysregulation of iron homeostasis in airways associated with persistent preschool wheezing.

BACKGROUND: Currently, there are no reliable clinical tools available to identify persistent asthma symptoms among preschool children with recurrent wheezing. We investigated iron homeostasis in the airways of preschoolers with recurrent wheezing and assessed whether iron homeostasis-related indices may reliably predict persistent wheezing. METHODS: Iron levels and mRNA expression levels of iron homeostasis molecules were examined in bronchoalveolar lavage samples from 89 preschoolers with recurrent wheezing and 56 controls, with a 12-month follow-up conducted. Risk factors for persistent wheezing were identified using least absolute shrinkage and selection operator and multivariate logistic regression. The addition of predictive values of iron indices to the modified Asthma Predictive Index (mAPI) or clinical predictors was determined using area under receiver operating characteristic curves (AUC). RESULTS: Preschoolers with recurrent wheezing had reduced iron levels in their airways, associated with significantly decreased expression of iron export molecule SLC40A1 and increased expression of iron intake factor TFR1 and iron storage factors FTH and FTL. Risk factors for persistent wheezing included mAPI positivity, iron predictors (lower expression of SLC40A1 and higher expression of FTL), and clinical predictors (aeroallergen sensitivity, shorter breastfeeding duration, and earlier age of first wheezing episode). The addition of information on iron predictors significantly enhanced the power of clinical predictors (AUC: 84%, increase of 12%) and mAPI (AUC: 81%, increase of 14%). CONCLUSIONS: Iron homeostasis is altered in the airways of preschoolers with recurrent wheezing. Adding information on iron-related indices to clinical information significantly improves accurate prediction of persistent wheezing in preschool-aged children.

Transcriptomic analysis identified SLC40A1 as a key iron metabolism-related gene in airway macrophages in childhood allergic asthma.

Introduction: Asthma is the most common chronic condition in children, with allergic asthma being the most common phenotype, accounting for approximately 80% of cases. Growing evidence suggests that disruption of iron homeostasis and iron regulatory molecules may be associated with childhood allergic asthma. However, the underlying molecular mechanism remains unclear. Methods: Three childhood asthma gene expression datasets were analyzed to detect aberrant expression profiles of iron metabolism-related genes in the airways of children with allergic asthma. Common iron metabolism-related differentially expressed genes (DEGs) across the three datasets were identified and were subjected to functional enrichment analysis. Possible correlations between key iron metabolism-related DEGs and type 2 airway inflammatory genes were investigated. Single-cell transcriptome analysis further identified major airway cell subpopulations driving key gene expression. Key iron metabolism-related gene SLC40A1 was validated in bronchoalveolar lavage (BAL) cells from childhood asthmatics with control individuals by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence. The intracellular iron content in BAL cells was assessed by Perls iron staining and the iron levels in BAL supernatant was measured by iron assay to assess airway iron metabolism status in childhood asthmatics. Results: Five common iron metabolism-related DEGs were identified, which were functionally related to iron homeostasis. Among these genes, downregulated SLC40A1 was strongly correlated with type 2 airway inflammatory markers and the gene signature of SLC40A1 could potentially be used to determine type 2-high and type 2-low subsets in childhood allergic asthmatics. Further single-cell transcriptomic analysis identified airway macrophages driving SLC40A1 expression. Immunofluorescence staining revealed colocalization of FPN (encoded by SLC40A1) and macrophage marker CD68. Down-regulation of SLC40A1 (FPN) was validated by qRT-PCR and immunofluorescence analysis. Results further indicated reduced iron levels in the BAL fluid, but increased iron accumulation in BAL cells in childhood allergic asthma patients. Furthermore, decreased expression of SLC40A1 was closely correlated with reduced iron levels in the airways of children with allergic asthma. Discussion: Overall, these findings reveal the potential role of the iron metabolism-related gene SLC40A1 in the pathogenesis of childhood allergic asthma.

Selection of DNA aptamer recognizing CD44 for high-efficiency capture of circulating tumor cells.

Cancer stem cells play critical roles in cancer progression, cancer invasion and metastasis, and cancer recurrence. CD44 is known as a specific surface marker of cancer stem cells, which has been well-studied in cancer invasion and metastasis. Herein, we successfully selected the DNA aptamers for recognizing CD44+ cells using Cell-SELEX strategy, in which the engineered CD44 overexpression cells were used as target cells for selection. The optimized aptamer candidate C24S showed high binding affinity with the Kd value of 14.54 nM and good specificity. Then, the aptamer C24S was employed to prepare the functional aptamer-magnetic nanoparticles (C24S-MNPs) for CTC capture. To investigate the capture efficiency and sensitivity of C24S-MNPs, series of cell capture tests were performed using artificial samples with 10-200 of HeLa cells spiked into 1 mL PBS or PBMCs isolated from 1 mL peripheral blood, obtaining an efficiency of 95% and 90%, respectively. More importantly, we finally explored the facility of C24S-MNPs for CTC detection in blood samples from clinical cancer patients, indicating a potential and feasible strategy for cancer diagnostic technology in clinical applications.

Determining whether the diagnostic value of B-ultrasound combined with contrast-enhanced ultrasound and shear wave elastography in breast mass-like and non-mass-like lesions differs: a diagnostic test.

Background: Mass-like (ML) and non-mass-like (NML) are two manifestations of breast lesions on ultrasound. Contrast-enhanced ultrasound (CEUS) can make up for the limitation of B-ultrasound (US) in the observation of focal blood flow, and shear wave elastography (SWE) can supplement the hardness information of the lesion. The present study aimed to analyze the characteristic manifestations of US, CEUS, and SWE in NML and ML breast and evaluate whether the diagnostic performance of these three ultrasound techniques differs in terms of differentiating between benign and malignant breast lesions. Methods: From January to August 2021, 382 patients (417 breast lesions) underwent US, CEUS, and SWE examinations. Of these, 204 women (218 breast lesions) were included in our study due to subsequent biopsy or surgery with pathological findings. The patients were divided into ML and NML groups according to the ultrasound characteristics, and the differences in multimodal ultrasound performance between benign and malignant NML and benign and malignant ML breast lesions were compared. The diagnostic performance of US, US + CEUS, US + SWE, US + CEUS + SWE for ML, NML and all breast lesions was evaluated by analyzing sensitivity, specificity and area under receiver operating characteristic (ROC) curve (AUC). Results: Pathologically, the 218 lesions included 96 malignant and 122 benign breast lesions. The sensitivity and specificity of US + CEUS + SWE in all lesion groups, ML group and NML group were 92.7% and 90.2%, 95.9% and 90.3%, 91.3% and 79.3%, respectively. In all breast group, AUCs of US + CEUS, US + SWE, US + CEUS + SWE were statistically different from AUC of US (P=0.0010, 0.0001, 0.0001). In the ML group, the AUC of US + CEUS, US + SWE, US + CEUS + SWE were statistically different from that of US (P=0.0120, 0.0008, 0.0002). In the NML group, there was a statistical difference between US + SWE and US AUC (P=0.0149). Conclusions: US, CEUS, and SWE have an important diagnostic value for benign and malignant ML and NML breast lesions. Multimodal ultrasound combined with US, CEUS, and SWE can improve the diagnostic efficacy in distinguishing between benign and malignant ML and NML lesions.

Proteomics comparison between mass-like and non-mass-like breast lesions.

Background: The proteomic differences between mass-like (ML) breast lesions and non-mass-like (NML) breast lesions were compared to explore the formation mechanism of NML ultrasonic morphological characteristics. Methods: From January to August 2021, tissue samples were collected from 10 patients with malignant ML (MML), 10 patients with malignant NML (MNML), 10 patients with benign ML (BML), and seven patients with benign NML (BNML). The proteomic differences between the BML and BNML groups and the MML and MNML groups were compared by data-independent acquisition (DIA) quantitative mass spectrometry. The differentially expressed proteins were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks analyses. Results: We identified a total of 623 significantly differentially expressed proteins in the MML/MNML group, and 167 significantly differentially expressed proteins in the BML/BNML group, with relative ratios >1.2 or <-0.83. The up-regulated differential proteins were more abundant in the tumor necrosis factor (TNF) signaling pathway in both the MML/MNML and BML/BNML groups, suggesting that the TNF signaling pathway may be related to the ultrasonic morphological characteristics of breast lesions. Dual specificity mitogen-activated protein kinase 3 (MP2K3), a protein factor in the TNF signaling pathway, exhibited significant upregulation in both the malignant and BML groups. Conclusions: The TNF signaling pathway may be associated with the ultrasonic morphological characteristics of breast lesions. MP2K3 is the up-regulated differential expression protein in the MML/MNML and BML/BNML groups, which may be related to the ultrasonic morphological characteristics of breast lesions.

Prostate cancer extracellular vesicle digital scoring assay - a rapid noninvasive approach for quantification of disease-relevant mRNAs.

Optimizing outcomes in prostate cancer (PCa) requires precision in characterization of disease status. This effort was directed at developing a PCa extracellular vesicle (EV) Digital Scoring Assay (DSA) for detecting metastasis and monitoring progression of PCa. PCa EV DSA is comprised of an EV purification device (i.e., EV Click Chip) and reverse-transcription droplet digital PCR that quantifies 11 PCa-relevant mRNA in purified PCa-derived EVs. A Met score was computed for each plasma sample based on the expression of the 11-gene panel using the weighted Z score method. Under optimized conditions, the EV Click Chips outperformed the ultracentrifugation or precipitation method of purifying PCa-derived EVs from artificial plasma samples. Using PCa EV DSA, the Met score distinguished metastatic (n = 20) from localized PCa (n = 20) with an area under the receiver operating characteristic curve of 0.88 (95% CI:0.78-0.98). Furthermore, longitudinal analysis of three PCa patients showed the dynamics of the Met scores reflected clinical behavior even when disease was undetectable by imaging. Overall, a sensitive PCa EV DSA was developed to identify metastatic PCa and reveal dynamic disease states noninvasively. This assay may complement current imaging tools and blood-based tests for timely detection of metastatic progression that can improve care for PCa patients.

Diagnostic performance of contrast-enhanced ultrasound in breast lesions: what diagnostic models could be used for lesions of different sizes?

Background: Previous studies show the size of lesions could affect the diagnostic accuracy of contrast-enhanced ultrasound (CEUS). It is unclear whether CEUS has good diagnostic performance for lesions ≤2.0 and ≤1.0 cm. It is beneficial for the early diagnosis to explore the application of CEUS in breast lesions of different sizes. This study aims to analyze the diagnostic performance of CEUS and explore diagnostic models better suited to breast lesions of different sizes. Methods: A total of 1,059 lesions (656 benign and 403 malignant) examined by ultrasound and CEUS with definite pathological results were included in this retrospective study and divided into training (n=847) and validation (n=212) sets. All lesions were divided into three groups according to size. Diagnostic models (M0: all lesions; M1: ≤1.0 cm, M2: >1.0-2.0 cm, and M3: >2.0 cm) were developed through logistic regression analyses of CEUS features from the training set. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC) and validated in the validation set. Results: The median age of patients was 45±11 years (range, 18-80 years). The AUC values of M0 combined with the Breast Imaging Reporting and Data System (BI-RADS) in the training and validation sets were 0.921 and 0.922, respectively (P=0.893). The AUC values of M0 combined with BI-RADS in the three groups were 0.844, 0.936 and 0.928 respectively. M0 was less effective in diagnosing lesions ≤1.0 cm (0.844 vs. 0.921, P=0.029). The AUC of M1 combined with BI-RADS for lesions ≤1.0 cm was higher than that of M0 (0.893 vs. 0.844, P=0.047), and M2 and M3 had no statistical difference in diagnostic performance when compared with M0 (P=0.243; P=0.246). Conclusions: The diagnostic performance of CEUS was closely related to lesion size. Establishing a new diagnostic model for lesions ≤1.0 cm can improve the CEUS diagnostic performance for breast lesions ≤1.0 cm.

Optimization of an Efficient Protoplast Transformation System for Transient Expression Analysis Using Leaves of Torenia fournieri.

Torenia fournieri (T. fournieri) is one of the most widely used horticultural flowers and is considered a potential model plant for the genetic investigation of ornamental traits. In this study, we optimized an efficient protocol for high efficiency preparation and transformation of T. fournieri protoplast. The transformation rate reached ~75% when a 35S:GFP construct was used for the transformation. Using this system, we characterized the subcellular localization of several TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factors (TFs), and found a distinct localization pattern between the CIN and CYC classes of TCP TFs. Furthermore, we also demonstrated the feasibility of the expression of dual luciferase assay system in T. fournieri protoplasts for the measurement of the activity of cis-regulatory elements. Taken together, a well-optimized transient expression system in T. fournieri protoplasts would be crucial for rapid exploration of the gene function or cis-regulatory elements.

A simplified scoring protocol to improve diagnostic accuracy with the breast imaging reporting and data system in breast magnetic resonance imaging.

Background: The breast imaging reporting and data system (BI-RADS) lexicon provides a standardized terminology for describing leision characteristics but does not provide defined rules for converting specific imaging features into diagnostic categories. The inter-reader agreement of the BI-RADS is moderate. In this study, we explored the use of a simplified protocol and scoring system for BI-RADS categorization which integrates the morphologic features (MF), kinetic time-intensity curve (TIC), and apparent diffusion coefficient (ADC) values with equal weights, with a view to providing a convenient and practical method for breast magnetic resonance imaging (MRI) and improving the inter-reader agreement and diagnostic performance of BI-RADS. Methods: This cross-sectional, retrospective, single-center study included 879 patients with 898 histopathologically verified lesions who underwent an MRI scan on a 3.0 Tesla GE Discovery 750 MRI scanner between January 1, 2017, and June 30, 2020. The BI-RADS categorization of the studied lesions was assessed according to the sum of the assigned scores (the presence of malignant MF, lower ADC, and suspicious TIC each warranted a score of +1). Total scores of +2 and +3 were classified as category 5, scores of +1 were classified as category 4, and scores of +0 but with other lesions of interest were classified as category 3. The receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity, and accuracy of this categorization were investigated to assess its efficacy and its consistency with pathology. Results: There were 472 malignant, 104 risk, and 322 benign lesions. Our simplified scoring protocol had high diagnostic accuracy, with an area under curve (AUC) value of 0.896. In terms of the borderline effect of pathological risk and category 4 lesions, our results showed that when risk lesions were classified together with malignant ones, the AUC value improved (0.876 vs. 0.844 and 0.909 vs. 0.900). When category 4 and 5 lesions were classified as malignant, the specificity, accuracy, and AUC value decreased (82.3% vs. 93.2%, 89.3% vs. 90.2%, and 0.876 vs. 0.909, respectively). Therefore, to improve the diagnostic accuracy of the protocol for BI-RADS categorization, only category 5 lesions should be considered to be malignant. Conclusions: Our simplified scoring protocol that integrates MF, TIC, and ADC values with equal weights for BI-RADS categorization could improve both the diagnostic performance of the protocol for BI-RADS categorization in clinical practice and the understanding of the benign-risk-malignant breast diseases.

Surgical management and prognosis of phyllodes tumors of the breast.

Background: Regardless of histological grade, phyllodes tumors (PTs) exhibit the potential of local recurrence. The National Comprehensive Cancer Network (NCCN) recommends wide local excision (WLE) with a 1 cm margin or more for borderline/malignant PTs but excisional biopsy for benign PTs. However, the treatment of benign PTs remains controversial and the clinicopathologic risk factors for the local recurrence is still unclear. Methods: We retrospectively analyzed 238 patients with PTs who underwent surgery at the Chinese PLA General Hospital from January 1, 2006 and April 30, 2020. We stratified our analysis according to histologic grade and explored the clinicopathologic factors to influence local recurrence (LR), including age, histologic grade, history of fibroadenoma, type of surgery [vacuum-assisted biopsy system (VABS), local excision (LE), wide local excision (WLE) and mastectomy]. Results: All 238 cases were categorized as benign (171, 71.8%), borderline (38, 16.0%), or malignant (29, 12.2%). The median follow-up was 50.2 months. In multivariate analysis, histologic grade (P<0.01) and history of fibroadenoma (P<0.01) were independent prognostic factors for LR. No difference existed in the recurrence rate of BPT treated with different surgical procedures (P=0.397), whereas a higher recurrence rate was found in VABS and LE subgroups than in WLE and mastectomy subgroups for borderline/malignant tumors (P<0.01). Conclusions: No association found between surgical modalities and LR rate for BPT. We suggested a "wait-and-watch" policy for patients with unexpected benign subtypes, instead of unnecessary re-excision. In addition, VABS or LE can be treated for BPT with small mass, whereas WLE or even mastectomy should be conducted for borderline/malignant PTs with large mass.

Folic Acid-Modified Fluorescent-Magnetic Nanoparticles for Efficient Isolation and Identification of Circulating Tumor Cells in Ovarian Cancer.

Ovarian cancer (OC) is a lethal disease occurring in women worldwide. Due to the lack of obvious clinical symptoms and sensitivity biomarkers, OC patients are often diagnosed in advanced stages and suffer a poor prognosis. Circulating tumor cells (CTCs), released from tumor sites into the peripheral blood, have been recognized as promising biomarkers in cancer prognosis, treatment monitoring, and metastasis diagnosis. However, the number of CTCs in peripheral blood is low, and it is a technical challenge to isolate, enrich, and identify CTCs from the blood samples of patients. This work develops a simple, effective, and inexpensive strategy to capture and identify CTCs from OC blood samples using the folic acid (FA) and antifouling-hydrogel-modified fluorescent-magnetic nanoparticles. The hydrogel showed a good antifouling property against peripheral blood mononuclear cells (PBMCs). The FA was coupled to the hydrogel surface as the targeting molecule for the CTC isolation, held a good capture efficiency for SK-OV-3 cells (95.58%), and successfully isolated 2-12 CTCs from 10 OC patients' blood samples. The FA-modified fluorescent-magnetic nanoparticles were successfully used for the capture and direct identification of CTCs from the blood samples of OC patients.

Development of Metal-Organic Framework-Based Dual Antibody Nanoparticles for the Highly Specific Capture and Gradual Release of Circulating Tumor Cells.

Circulating tumor cells (CTCs) have been well-established as promising biomarkers that can be leveraged to gauge the prognosis of patients with cancers and to guide patient treatment efforts. Although the scarcity of CTCs within peripheral circulation and the associated phenotypic changes that they exhibit owing to the epithelial-mesenchymal transition (EMT) process make the reliable isolation of these cells very challenging. Recently, several studies have discussed platforms capable of mediating the efficient and sensitive isolation of CTCs, but these approaches are nonetheless subject to certain limitations that preclude their clinical application. For example, these platforms are poorly-suited to minimizing damage in the context of cellular capture and release or the in vitro culture of captured cells for subsequent molecular analyses, which would better enable clinicians to select appropriate precision treatments on an individualized basis. In this study, we report the layer-by-layer assembly approach to synthesize a novel composite nanomaterial consisting of modified zirconium-based metal-organic-frameworks (MOFs) on the surface of magnetic beads with dual antibody surface modifications capable of capturing CTCs without being hampered by the state of cellular EMT process. Our analyses indicated that these dual antibody-modified nanomaterials exhibited greater capture efficiency than that observed for single antibody. Importantly, captured cells can be gradually released following capture and undergo subsequent in vitro proliferation following water molecule-induced MOF structural collapse. This release mechanism, which does not require operator intervention, may be effective as a means of minimizing damage and preserving cellular viability such that cells can be more reliably utilized for downstream molecular analyses and associated treatment planning. To further confirm the potential clinical applicability of the developed nanomaterial, it was successfully utilized for capturing CTCs from peripheral blood samples collected from cases diagnosed with gastrointestinal tumors.

Endoscopic transcanal facial nerve decompression in Bell's palsy: A pilot study.

PURPOSE: To explore the surgical effects of endoscopic facial nerve decompression in Bell's palsy. MATERIALS AND METHODS: This retrospective study included 15 patients with Bell's palsy. All had grade VI (House-Brackmann grading system) complete unilateral facial paralysis before surgery and a >95% reduction in amplitude on electroneurography testing compared to the unaffected side. Their MRI results indicated perineural edema in the geniculate ganglion area. Endoscopic decompression surgery was performed soon after they presented at our hospital. The time between onset of facial paralysis and surgery ranged from 25 to 93 days. All patients had no relevant surgical history or ear diseases. RESULTS: At 1-year follow-up, 13 of the 15 (87%) patients had recovered to normal or near-normal facial function (House-Brackmann grade I-II), and all patients had reached House-Brackmann grade III or lower facial function. No obvious air-bone gap or sensorineural hearing loss occurred after surgery, and there were no severe complications or synkinesis. CONCLUSIONS: Endoscopic transcanal facial nerve decompression provides a less traumatic and improved exposure of the geniculate ganglion, and may also help prevent permanent severe facial sequela. Results of intraoperative facial nerve stimulation may be related to the length of time required for recovery. The optimal time of surgery after onset of paralysis needs to be investigated further, to identify a post-drug surgical therapy which may be more acceptable for patients. Patients' response to conservative treatments should be assessed as soon as possible so as not to delay surgery.

Circulating tumor cells in colorectal cancer in the era of precision medicine.

Colorectal cancer (CRC) is one of the main causes of cancer-related morbidity and mortality across the globe. Although serum biomarkers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA-199) have been prevalently used as biomarkers in various cancers, they are neither very sensitive nor highly specific. Repeated tissue biopsies at different times of the disease can be uncomfortable for cancer patients. Additionally, the existence of tumor heterogeneity and the results of local biopsy provide limited information about the overall tumor biology. Against this backdrop, it is necessary to look for reliable and noninvasive biomarkers of CRC. Circulating tumor cells (CTCs), which depart from a primary tumor, enter the bloodstream, and imitate metastasis, have a great potential for precision medicine in patients with CRC. Various efficient CTC isolation platforms have been developed to capture and identify CTCs. The count of CTCs, as well as their biological characteristics and genomic heterogeneity, can be used for the early diagnosis, prognosis, and prediction of treatment response in CRC. This study reviewed the existing CTC isolation techniques and their applications in the clinical diagnosis and treatment of CRC. The study also presented their limitations and provided future research directions.