Efficacy and safety of intracoronary pro-urokinase combined with low-pressure balloon pre-dilatation during percutaneous coronary intervention in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: The efficacy and safety of low-pressure balloon pre-dilatation before intracoronary pro-urokinase (pro-UK) in preventing no-reflow during percutaneous coronary intervention (PCI) remains unknown. This study aimed to evaluate the clinical outcomes of intracoronary pro-UK combined with low-pressure balloon pre-dilatation in patients with anterior ST-segment-elevation myocardial infarction (STEMI). METHODS: This was a randomized, single-blind, investigator-initiated trial that included 179 patients diagnosed with acute anterior STEMI. All patients were eligible for PCI and were randomized into two groups: intracoronary pro-UK combined with (ICPpD group, n = 90) or without (ICP group, n = 89) low-pressure balloon pre-dilatation. The main efficacy endpoint was complete epicardial and myocardial reperfusion. The safety endpoints were major adverse cardiovascular events (MACEs), which were analyzed at 12 months follow-up. RESULTS: Patients in the ICPpD group presented significantly higher TIMI myocardial perfusion grade 3 (TMPG3) compared to those in the ICP group (77.78% versus 68.54%, P = 0.013), and STR ≥ 70% after PCI 30 min (34.44% versus 26.97%, P = 0.047) or after PCI 90 min (40.0% versus 31.46%, P = 0.044). MACEs occurred in 23 patients (25.56%) in the ICPpD group and in 32 patients (35.96%) in the ICP group. There was no difference in hemorrhagic complications during hospitalization between the groups. CONCLUSION: Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI. TRIAL REGISTRATION: 2019xkj213.

Multi-view graph network learning framework for identification of major depressive disorder.

Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging (rs-fMRI) exhibits non-Euclidean topological structures, which have pathological foundations and serve as ideal objective data for intelligent diagnosis of major depressive disorder (MDD) patients. Additionally, the fully connected FC demonstrates uniform spatial structures. To learn and integrate information from these two structural forms for a more comprehensive identification of MDD patients, we propose a novel hierarchical learning structure called Multi-View Graph Neural Network (MV-GNN). In MV-GNN, the collaborative FC of subjects is filtered and reconstructed from topological view to obtain the reconstructed FC, incorporating various threshold values to calculate the topological attributes of brain regions. ROC analysis is performed on the average scores of these attributes for MDD and healthy control (HC) groups to determine an efficient threshold. Group differences analysis is conducted on the efficient topological attributes of brain regions, followed by their selection. These efficient attributes, along with the reconstructed FC, are combined to construct a graph view using self-attention graph pooling and graph convolutional neural networks, enabling efficient embedding. To extract efficient FC pattern difference information from spatial view, a dual leave-one-out cross-feature selection method is proposed. It selects and extracts relevant information from uniformly sized FC structures' high-dimensional spatial features, constructing a relationship view between brain regions. This approach incorporates both the whole graph topological view and spatial relationship view in a multi-layered structure, fusing them using gating mechanisms. By incorporating multiple views, it enhances the inference of whether subjects suffer from MDD and reveals differential information between MDD and HC groups across different perspectives. The proposed model structure is evaluated through leave-one-site cross-validation and achieves an average accuracy of 65.61% in identifying MDD patients at a single-center site, surpassing state-of-the-art methods in MDD recognition. The model provides valuable discriminatory information for objective diagnosis of MDD and serves as a reference for pathological foundations.

Large dynamic range dual-mode pH sensors via dye-doped ionic liquid fiber optofluidic lasers.

We report a fiber optofluidic laser (FOFL) using an RhB-doped ionic liquid (BmimPF6) as the gain medium and explore its application for large dynamic range highly sensitive pH sensing. Due to the high Q-factor of the FOFL and the unique merits of BmimPF6, lasing emission presents a threshold of only 0.61 µJ mm-1. Particularly, lasing emission behaviors are strongly dependent on the pH value of the gain medium, i.e., in the pH range 4.28-6.37, the lasing central wavelength blue-shifts monotonically with a sensitivity as high as 5.02 nm per pH unit, which we attribute to the conversion of the cationic form of RhB to the zwitterionic form caused by the deprotonation of the COOH group. Under alkaline conditions (pH 7.20-11.17), the lasing emission intensity exhibits a significant decrease and the corresponding lasing central wavelength is also blue-shifted due to the solvent effect. The sensitivity based on the wavelength shift is 3.03 nm per pH unit, which is 4-fold higher than that of fluorescence-based sensing, while the sensitivity based on the variation of the lasing emission intensity is almost three orders of magnitude higher than that of fluorescence-based sensing. Our work presents a novel dual sensing paradigm in response to different pH conditions, which can greatly improve the reliability and discrimination of pH sensing.

CD73 mitigates hepatic damage in alcoholic steatohepatitis by regulating PI3K/AKT-mediated hepatocyte pyroptosis.

BACKGROUND: Alcohol use is a major risk factor for death and disability, resulting in a significant global disease burden. Alcoholic steatohepatitis (ASH) reflects an acute exacerbation of alcoholic liver disease (ALD) and is a growing health care and economic burden worldwide. Pyroptosis plays a central role in the pathogenesis of ASH. Nt5e (CD73) is a cell surface ecto-5'-nucleotidase, which is a key enzyme that converts the proinflammatory signal ATP to the anti-inflammatory mediator adenosine (ADO). Studies have found that CD73 is involved in multiple diseases and can alleviate gasdermin D (GSDMD)-mediated pyroptosis; however, its role and mechanism in ASH are not explicit. AIM: To investigate the role and mechanisms of CD73-mediated hepatocyte pyroptosis in alcohol-induced liver injury through in vivo and in vitro experiments. METHODS: CD73 knockout (CD73-/-) mice, wild-type (WT) mice, and AML-12 cells were used to evaluate the effect of CD73 on hepatocyte pyroptosis in vivo and in vitro. A combination of molecular and histological methods was performed to assess pyroptosis and investigate the mechanism both in vivo and in vitro. RESULTS: The protein expression of CD73 and pyroptosis pathway-associated genes was increased significantly in hepatocyte injury model both in vivo and in vitro. In vivo, CD73 knockout dramatically aggravated inflammatory damage, lipid accumulation, and hepatocyte pyroptosis in the liver. In vitro, overexpression of CD73 by pEGFP-C1/CD73 can decrease NLRP3 inflammasome activation and pyroptosis in hepatocytes. Further analysis revealed that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is a possible mechanism of CD73 regulation. Meanwhile, this pathological process was inhibited after the use of PI3K inhibitors. CONCLUSION: Our results show a novel function of CD73 regulates hepatocytes pyroptosis and highlights the therapeutic opportunity for reducing the disease process in ALD.

Intelligent diagnosis of major depression disease based on multi-layer brain network.

Introduction: Resting-state brain network with physiological and pathological basis has always been the ideal data for intelligent diagnosis of major depression disease (MDD). Brain networks are divided into low-order networks and high-order networks. Most of the studies only use a single-level network to classify while ignoring that the brain works cooperatively with different levels of networks. This study hopes to find out whether varying levels of networks will provide complementary information in the process of intelligent diagnosis and what impact will be made on the final classification results by combining the characteristics of different networks. Methods: Our data are from the REST-meta-MDD project. After the screening, 1,160 subjects from ten sites were included in this study (597 MDD and 563 normal controls). For each subject, we constructed three different levels of networks according to the brain atlas: the traditional low-order network based on Pearson's correlation (low-order functional connectivity, LOFC), the high-order network based on topographical profile similarity (topographical information-based high-order functional connectivity, tHOFC) and the associated network between them (aHOFC). Two sample t-test is used for feature selection, and then features from different sources are fused. Finally, the classifier is trained by a multi-layer perceptron or support vector machine. The performance of the classifier was evaluated using the leave-one-site cross-validation method. Results: The classification ability of LOFC is the highest among the three networks. The classification accuracy of the three networks combined is similar to the LOFC network. These are seven features chosen in all networks. In the aHOFC classification, six features were selected in each round but not seen in other classifications. In the tHOFC classification, five features were selected in each round but were unique. These new features have crucial pathological significance and are essential supplements to LOFC. Conclusion: A high-order network can provide auxiliary information for low-order networks but cannot improve classification accuracy.

CD73/NT5E-mediated ubiquitination of AURKA regulates alcohol-related liver fibrosis via modulating hepatic stellate cell senescence.

Alcohol-related liver disease (ALD) is the most common chronic liver disease worldwide; however, no effective treatment to prevent the progression of alcohol-related liver fibrosis (ALF) is available. CD73/NT5E, a nucleotidase, controls cellular homeostasis by combining extracellular purinergic signaling with intracellular kinase activity and gene transcription and is associated with cell proliferation, differentiation, and death. In this study, we demonstrated that CD73/NT5E had a more significant regulatory effect on the activation, proliferation, and apoptosis of HSCs compared with that of CD39/ENTPD1. We examined the expression of CD73/NT5E in the normal and fibrotic human livers. The absence of CD73/NT5E was protective in mouse models of ALF. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that CD73/NT5E overexpression was related to the p53 signaling pathway, which regulates cell senescence. Proteins interacting with p53 were predicted using the STRING database. The overlap between proteomic analysis and STRING databases was for Aurora kinase A (AURKA), a cell cycle-regulated kinase. Coimmunoprecipitation (co-IP) assay and molecular docking confirmed that CD73/NT5E directly interacted with AURKA. We found that overexpression of CD73/NT5E inhibited AURKA ubiquitination, whereas p53 signaling was downregulated. Mechanistically, CD73/NT5E regulated ALF and the activation and senescence of stellate cells by binding to AURKA. These findings indicate that CD73/NT5E is a potential therapeutic target for ALF.

CD73 aggravates alcohol-related liver fibrosis by promoting autophagy mediated activation of hepatic stellate cells through AMPK/AKT/mTOR signaling pathway.

CD73 is a membrane-bound glycoprotein that can dephosphorylate AMP to adenosine. Increasing evidence has shown that CD73 is involved in the occurrence and development of liver fibrosis. However, the potential mechanism by which CD73 affects the progression of alcohol-related liver fibrosis (ALF) remains unknown. This study aimed to examine the role and mechanism of CD73 in autophagy in HSC-T6 cells and its role in ALF in mice that treated with alcohol plus CCl4. We found that CD73 knockout reduced serum alanine aminotransferase and aspartate aminotransferase levels and decreased liver injury and collagen deposition. Furthermore, autophagy-related indicators were downregulated in the liver fibrosis tissues of CD73-/- (EtOH + CCl4) mice. In vitro, the expression of CD73 and autophagy increased in activated HSC-T6 cells. Autophagy inhibitor, 3-methyladenine, reduced autophagy and activation of acetaldehyde-induced HSC-T6 cells. When using CD73-siRNA, autophagy in HSC-T6 cells was found to be downregulated. However, the CD73 plasmid increased the activation and autophagy of hepatic stellate cells (HSCs). In addition, CD73 induced autophagy through the AMPK/AKT/mTOR pathway, which is characterized by an increase in the ratio of P-AMPKα/AMPKα and a decrease in the ratio of P-AKT/AKT and P-mTOR/mTOR. Our study found that CD73 promotes HSCs activation by regulating autophagy through the AMPK/AKT/mTOR signaling pathway.

CD73-Adenosine A1R Axis Regulates the Activation and Apoptosis of Hepatic Stellate Cells Through the PLC-IP3-Ca2+/DAG-PKC Signaling Pathway.

Alcohol-related liver fibrosis (ALF) is a form of alcohol-related liver disease (ALD) that generally occurs in response to heavy long-term drinking. Ecto-5'-nucleotidase (NT5E), also known as CD73, is a cytomembrane protein linked to the cell membrane via a GPI anchor that regulates the conversion of extracellular ATP to adenosine. Adenosine and its receptors are important regulators of the cellular response. Previous studies showed that CD73 and adenosine A1 receptor (A1R) were important in alcohol-related liver disease, however the exact mechanism is unclear. The aim of this study was to elucidate the role and mechanism of the CD73-A1R axis in both a murine model of alcohol and carbon tetrachloride (CCl4) induced ALF and in an in vitro model of fibrosis induced by acetaldehyde. The degree of liver injury was determined by measuring serum AST and ALT levels, H & E staining, and Masson's trichrome staining. The expression levels of fibrosis indicators and PLC-IP3-Ca2+/DAG-PKC signaling pathway were detected by quantitative real-time PCR, western blotting, ELISA, and calcium assay. Hepatic stellate cell (HSC) apoptosis was detected using the Annexin V-FITC/PI cell apoptosis detection kit. Knockdown of CD73 significantly attenuated the accumulation of α-SMA and COL1a1 damaged the histological architecture of the mouse liver induced by alcohol and CCl4. In vitro, CD73 inhibition attenuated acetaldehyde-induced fibrosis and downregulated A1R expression in HSC-T6 cells. Inhibition of CD73/A1R downregulated the expression of the PLC-IP3-Ca2+/DAG-PKC signaling pathway. In addition, silencing of CD73/A1R promoted apoptosis in HSC-T6 cells. In conclusion, the CD73-A1R axis can regulate the activation and apoptosis of HSCs through the PLC-IP3-Ca2+/DAG-PKC signaling pathway.

High sensitivity pH sensing by using a ring resonator laser integrated into a microfluidic chip.

We present a chip-scale integrated pH sensor with high sensitivity by using an optofluidic ring resonator (OFRR) laser. An optical fiber with a high refractive index (RI) is employed both as an optical cavity and the sensing reactor along a microchannel, while disodium fluorescein (DSF) aqueous solution with a low RI is served as the cladding gain medium and fluorescent probes. The pump light is introduced along the fiber axis and guided by the total internal reflection at the fiber/cladding interface. The evanescent field of the pump light extends out of the fiber surface and efficiently excites the dye molecules residing in the evanescent field region of the Whispering Gallery Modes (WGMs) of the OFRRs to produce lasing emission. This pumping scheme provides a uniform excitation to the gain medium and significantly increases the signal-to-noise ratio, ensuring a low lasing threshold and highly sensitive sensing. The lasing threshold property under different pH conditions is experimentally and theoretically conducted to evaluate the sensing performance, which shows that the lasing threshold highly depends on the pH value of the cladding solution due to the increasing deprotonation process. We further verify that the intensity of the lasing emission and the pH value shows good linearity in the pH range 6.51-8.13, with a 2-order-of-magnitude sensitivity enhancement compared to fluorescence measurement. The proposed OFRR lasing platform shows excellent robustness and low sample consumption, providing a powerful sensing strategy in medicine, and hazardous/toxic/volatile sensing, which require label-free, real-time, and in situ detection.

Sexual, physical, and overall adverse effects in patients treated with 5α-reductase inhibitors: a systematic review and meta-analysis.

Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64-2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74-2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80-2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.

Animal models of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms are common clinical concerns that affect aging men all over the world. The underlying molecular and cellular mechanisms remain elusive. Over the past few years, a number of animal models of BPH, including spontaneous model, BPH-induction model, xenograft model, metabolic syndrome model, mechanical obstruction model, and transgenic model, have been established that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outlined the present status quo for animal models of BPH, comparing the pros and cons with respect to their ability to mimic the etiological, histological, and clinical hallmarks of BPH and discussed their applicability for future research.

A novel cell-free single-molecule unique primer extension resequencing (cf-SUPER) technology for bladder cancer non-invasive detection in urine.

BACKGROUND: The clinical diagnostic method for bladder cancer is cystoscopy, an invasive, expensive and inconvenient clinical test. Using urinary cell-free DNA (cfDNA) to develop non-invasive test for bladder cancer was a promising liquid biopsy. METHODS: To improve the using rate of cfDNA template and decrease the PCR bias for liquid biopsy using urinary cfDNA, we developed a cell-free single-molecule unique primer extension resequencing (cf-SUPER) technology which was done for 29 matched urinary cfDNA and tumor DNA samples of bladder cancer patients to evaluate consistency of mutation profiles. Then, a 22 high mutational frequence genes was selected to form an uriprier panel, which was analyzed in 100 patients (47 bladder cancer cases and 53 controls) using cf-SUPER technology. This performance of the technology was evaluated using bioinformatic tools and clinical samples. RESULTS: The study showed that cf-SUPER technology can accurately detect mutations with allele fractions even low as 0.01% and the DNA input as low as 1 ng. The consistency of mutation profiles and clinical pathological diagnose between 29 matched urinary cfDNA and tumor DNA samples was respectively 82.76% and 89.66% by using cf-SUPER technology. Using cf-SUPER technology, the sensitivity and specificity were 98%, 94% respectively for uriprier panel in non-invasive test. CONCLUSIONS: The preliminary work shows that cf-SUPER technology will be a promising method for liquid biopsy. Focusing urinary cfDNA, the non-invasive diagnose and monitoring of bladder cancer can come true by using cf-SUPER technology.

Proposal of the 3O (Obstruction, Ureteric Orifice, and Outcome) Subclassification System Associated with Obstructed Hemivagina and Ipsilateral Renal Anomaly (OHVIRA).

STUDY OBJECTIVE: To propose a "3O" (obstruction, ureteric orifice, and outcome) subclassification system associated with obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). DESIGN: Retrospective case series. SETTING: Xiangya Hospital, Central South University, Changsha, Hunan, China. PARTICIPANTS: A total of 26 women with obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) over a 9-year period. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: In all cases, the obstruction, ureteric orifice, outcome and surgical strategy were reviewed. RESULTS: In our study, the "obstruction" category included 14 cases of blind hemivagina, 8 cases of buttonhole septum, 3 cases of cervical fistula, and 1 case of cervical atresia. A total of 25 patients with vaginal obstruction underwent resection of the vaginal septum. The patient with cervical atresia underwent a failed cervicoplasty, followed by hemi-hysterectomy. The "ureteric orifice" category included 24 cases of absent ureter with no orifice, as well as 2 cases of ureteric orifice emptying into the obstructed hemivagina. The 2 patients were treated with laparoscopic extirpation of the ectopic ureter and renal moiety. Regarding the "outcome" category, 5 patients with severe recurrent hematometra, hematosalpinx, and ovarian endometrioma underwent hemi-hysterectomy, salpingectomy, and cystectomy of the ovarian endometrioma. Both patients (1 with a septate uterus and 1 with a bicornuate uterus) who experienced recurrent abortion accepted uterine correction. CONCLUSION: We provide new insights into the anatomical variants of this rare syndrome with the relevant surgical implications. Magnetic resonance imaging is the most useful tool in 3O diagnosis.

Neoadjuvant Chemotherapy Benefits Survival in High-Grade Upper Tract Urothelial Carcinoma: A Propensity Score-Based Analysis.

BACKGROUND: To evaluate the benefit of neoadjuvant chemotherapy (NAC) for survival in high-grade upper tract urothelial carcinoma (UTUC), a propensity score-based analysis was performed with high-grade UTUC patients from multiple urologic centers. METHODS: From three urologic centers, 48 high-grade UTUC patients who received chemotherapy followed by surgery (NAC group) and 72 high-grade UTUC patients who underwent initial surgery (no-NAC group) were involved in a propensity score-based analysis. After propensity score-based (1:1) matching, 37 patients receiving NAC and 37 patients not receiving NAC were followed. RESULTS: The patients who received NAC had improved disease-free survival (DFS) and overall survival (OS), with a 3-year DFS rate of 78.4% and an OS rate of 86.5% versus a 3-year DFS rate of 51.4% and an OS rate of 62.2% for those treated with initial surgery (P = 0.018 and P = 0.02, respectively). In the multivariate analysis, the NAC group had a lower risk for mortality [DFS hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.10-0.62; P = 0.003; OS HR 0.22; 95% CI 0.085-0.57; P = 0.002]. The analysis of patient survival in matched subgroups showed that NAC was beneficial in terms of the 3-year DFS for the group with a cT of 3 or higher (DFS HR 0.37; 95% CI 0.14-0.94; P = 0.036) and the group that had tumor with hydronephrosis (DFS HR 0.31; 95% CI 0.11-0.87; P = 0.026). CONCLUSION: The study showed that NAC may be considered as an effective addition to surgery for the treatment in high-grade UTUC patients.

Long noncoding RNA DNM3OS promotes prostate stromal cells transformation via the miR-29a/29b/COL3A1 and miR-361/TGFß1 axes.

Transforming growth factor-ß1 (TGFß1)-induced differentiation into and the activation of myofibroblasts have been regarded as critical events in benign prostatic hyperplasia (BPH); however, the underlying mechanisms of BPH pathogenesis remain unclear. Microarray profiling, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and Gene Ontology (GO) enrichment analysis were performed to confirm the candidate genes and long non-coding RNA (lncRNAs) related to BPH. Collagen Type III (COL3A1) was significantly upregulated by TGFß1 in prostate stromal cells (PrSCs) and might be involved in DNM3OS function in myofibroblasts upon TGFß1 stimulation. Upon TGFß1 stimulation, COL3A1 protein was decreased by DNM3OS silencing. miR-29a and miR-29b could directly bind to the DNM3OS and COL3A1 3' untranslated region (UTR)s to negatively regulate their expression, and by serving as a competing endogenous RNAs (ceRNA), DNM3OS competed with COL3A1 for miR-29a/29b binding, therefore counteracting miR-29a/29b-mediated COL3A1 suppression. The effect of DNM3OS silencing on ECM components and TGFß1 downstream signaling was similar to that of the TGFß1 inhibitor SB431542. miR-361 could target DNM3OS and TGFß1; DNM3OS competed for miR-361 binding to counteract miR-361-mediated TGFß1 suppression. In conclusion, we identified DNM3OS as a specifically-upregulated lncRNA upon TGFß1 stimulation in PrSCs; by serving as a ceRNA for the miR-29a/29b cluster and miR-361, DNM3OS eliminated miRNA-mediated suppression of COL3A1 and TGFß1, thereby promoting TGFß1-induced PrSC transformation into myofibroblasts.

ERα-mediated alterations in circ_0023642 and miR-490-5p signaling suppress bladder cancer invasion.

Epidemiological studies show obvious gender differences in the incidence and the prognosis of bladder cancer (BCa). Estrogen receptor alpha (ERα) was recently shown to play a protective role in BCa. However, the mechanisms by which ERα mediates BCa progression need to be further elucidated. In the present study, we explored the mechanisms by which ERα inhibits BCa invasion by modulating circRNA levels. ERα suppressed BCa invasion by decreasing circ_0023642 expression. Chromatin immunoprecipitation (ChIP) and luciferase assays revealed that ERα reduced circ_0023642 expression by regulating the expression of its host gene, UVRAG, at the transcriptional level. ERα decreased circ_0023642 levels and subsequently increased miR-490-5p expression, resulting in decreased EGFR expression to suppress BCa cell invasion. Circ_0023642 was demonstrated to directly bind to miR-490-5p. Notably, miR-490-5p regulated EGFR expression by binding to the miR-490-5p-binding site located in the 3'-untranslated region (UTR) of the EGFR mRNA. Preclinical studies using an in vivo mouse model also confirmed that this ERα/circ_0023642/miR-490-5p/EGFR signaling pathway suppressed BCa progression. Altogether, this newly identified pathway may serve as the basis for developing novel therapeutic strategies to treat BCa.