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Abstract Genetic variations in the ovine ovulation rate, which are associated with the FecB mutation, provide useful models by which to explore the mechanisms regulating the development of mammalian antral follicles. In order to study the effects of the FecB mutation on cumulus cell differentiation, preovulatory follicles were aspirated and cumulus cells were isolated from three FecB genotypes (homozygous, heterozygous and wild type) of Small Tail Han (STH) sheep superstimulated with FSH. Transcriptome information from tens of thousands of cumulus cells was determined with the 10 × Genomics single-cell RNA-seq technology. Under the superovulation treatment, the observed number of preovulatory follicles in the ovaries of FecB carriers was still significantly higher than that in the wild-type (P

Abstract The current challenge in effectively treating atrial fibrillation (AF) stems from a limited understanding of the intricate structure of the human atria. The objective and quantitative interpretation of the right atrium (RA) in late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) scans relies heavily on its precise segmentation. Leveraging the potential of artificial intelligence (AI) for RA segmentation presents a promising solution. However, the successful implementation of AI in this context necessitates access to a substantial volume of annotated LGE-MRI images for model training. In this paper, we present a comprehensive 3D cardiac dataset comprising 50 high-resolution LGE-MRI scans, each meticulously annotated at the pixel level. The annotation process underwent rigorous standardization through crowdsourcing among a panel of medical experts, ensuring the accuracy and consistency of the annotations. Our dataset represents a significant contribution to the field, providing a valuable resource for advancing RA segmentation methods.

Abstract Background Infective endocarditis (IE) is a disease with high in-hospital mortality. The objective of the present investigation was to develop and validate a nomogram that precisely anticipates in-hospital mortality in ICU individuals diagnosed with infective endocarditis. Methods Retrospectively collected clinical data of patients with IE admitted to the ICU in the MIMIC IV database were analyzed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify potential hazards. A logistic regression model incorporating multiple factors was established, and a dynamic nomogram was generated to facilitate predictions. To assess the classification performance of the model, an ROC curve was generated, and the AUC value was computed as an indicator of its diagnostic accuracy. The model was subjected to calibration curve analysis and the Hosmer–Lemeshow (HL) test to assess its goodness of fit. To evaluate the clinical relevance of the model, decision-curve analysis (DCA) was conducted. Results The research involved a total of 676 patients, who were divided into two cohorts: a training cohort comprising 473 patients and a validation cohort comprising 203 patients. The allocation ratio between the two cohorts was 7:3. Based on the independent predictors identified through LASSO regression, the final selection for constructing the prediction model included five variables: lactate, bicarbonate, white blood cell count (WBC), platelet count, and prothrombin time (PT). The nomogram model demonstrated a robust diagnostic ability in both the cohorts used for training and validation. This is supported by the respective area under the curve (AUC) values of 0.843 and 0.891. The results of the calibration curves and HL tests exhibited acceptable conformity between observed and predicted outcomes. According to the DCA analysis, the nomogram model demonstrated a notable overall clinical advantage compared to the APSIII and SAPSII scoring systems. Conclusions The nomogram developed during the study proved to be highly accurate in forecasting the mortality of patients with IE during hospitalization in the ICU. As a result, it may be useful for clinicians in decision-making and treatment.

Abstract Background Recurrent malignant pleural effusion (MPE) resulting from non‐small‐cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain. Methods 16 NSCLC patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumours. Non‐recurrent or recurrent MPE was determined after 3–6 weeks of treatments. The status of MPE was verified by computer tomography (CT) and cytopathology, and the baseline pleural fluids were collected for single‐cell RNA sequencing (scRNA‐seq). Samples were then integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction (qPCR) in a larger MPE cohort from the authors' centre (n = 64). Results The scRNA‐seq revealed that 33 590 cells were annotated as 7 major cell types and further characterized into 14 cell clusters precisely. The cell cluster C1, classified as Epithelial Cell Adhesion Molecule (EpCAM)+ metastatic cancer cell and correlated with activation of tight junction and adherence junction, was significantly enriched in the recurrent MPE group, in which Claudin‐4 (CLDN4) was identified. The subset cell cluster C3 of C1, which was enriched in recurrent MPE and demonstrated a phenotype of ameboidal‐type cell migration, also showed a markedly higher expression of CLDN4. Meanwhile, the expression of CLDN4 was positively correlated with E74 Like ETS Transcription Factor 3 (ELF3), EpCAM and Tumour Associated Calcium Signal Transducer 2 (TACSTD2), independent of driver‐gene status. CLDN4 was also found to be associated with the expression of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Vascular Endothelial Growth Factor A (VEGFA), and the cell cluster C1 was the major mediator in cellular communication of VEGFA signalling. In the extensive MPE cohort, a notably increased expression of CLDN4 in cells from pleural effusion among patients diagnosed with recurrent MPE was observed, compared with the non‐recurrent group, which was also associated with a trend towards worse overall survival (OS). Conclusions CLDN4 could be considered as a predictive marker of recurrent MPE among patients with advanced NSCLC. Further validation for its clinical value in cohorts with larger sample size and in‐depth mechanism studies on its biological function are warranted. Trial registration Not applicable.

Background Immunotherapy for malignant tumors has made great progress, but many patients do not benefit from it. The complex intratumoral heterogeneity (ITH) hindered the in-depth exploration of immunotherapy. Conventional bulk sequencing has masked intratumor complexity, preventing a more detailed discovery of the impact of ITH on treatment efficacy. Hence, we initiated this study to explore ITH at the multi-omics spatial level and to seek prognostic biomarkers of immunotherapy efficacy considering the presence of ITH.Methods Using the segmentation strategy of digital spatial profiling (DSP), we obtained differential information on tumor and stromal regions at the proteomic and transcriptomic levels. Based on the consideration of ITH, signatures constructed by candidate proteins in different regions were used to predict the efficacy of immunotherapy.Results Eighteen patients treated with a bispecific antibody (bsAb)-KN046 were enrolled in this study. The tumor and stromal areas of the same samples exhibited distinct features. Signatures consisting of 11 and 18 differentially expressed DSP markers from the tumor and stromal areas, respectively, were associated with treatment response. Furthermore, the spatially resolved signature identified from the stromal areas showed greater predictive power for bsAb immunotherapy response (area under the curve=0.838). Subsequently, our stromal signature was validated in an independent cohort of patients with non-small cell lung cancer undergoing immunotherapy.Conclusion We deciphered ITH at the spatial level and demonstrated for the first time that genetic information in the stromal region can better predict the efficacy of bsAb treatment.Trial registration number NCT03838848.

Objectives We investigated whether the totally video-assisted thoracoscopic mitral valve surgery provides superior clinical outcomes and less inflammatory injury reaction compared with conventional sternotomy. Methods A total of 504 consecutive patients admitted for mitral valve surgery from May 2014 through May 2019 in a single center were retrospectively analyzed according to two distinct procedure approach: the totally video-assisted thoracoscopic approach (group A, n = 127) and standard median sternotomy (group B, n = 377). The primary end point was the durations of cardiopulmonary bypass, aortic cross-clamping, the ventilation time and intensive care unit of stay; the secondary endpoints included inflammation indexes like high sensitivity C-reactive protein, neutrophil-lymphocyte ratio and metabolic injury parameters cardiac Troponin and lactate. Results There was only one in-hospital death due to diffuse intravascular coagulation in group A, but similar complications such as repair failure, re-thoracotomy and stroke in both groups. The durations of cardiopulmonary bypass and aortic cross-clamping were significantly longer in group A. In contrast, ventilation time and intensive care unit of stay were shortened compared with these in group B. In addition, postoperative equivalent lactate clearance but lower high sensitivity C-reactive protein, neutrophil-lymphocyte ratio and cardiac Troponin level was in group A than those in group B within postoperative 24 hours(P

Cardiovascular diseases (CVDs) continue to be the leading cause of health problems around the world. Because of its unique properties, reactive oxygen species (ROS)-based nanotechnology offers novel solutions to the diagnosis and treatment of CVDs. In order to identify and further promote the development of ROS-based nanotechnology in CVDs, we here provide a bibliometric analysis. 701 eligible articles about the ROS–based nanotechnology for CVD up to May 26th, 2022, were taken from the Web of Science Core Collection database. The VOSviewer was used to analyze annual publications, countries/institutions, funding agencies, journals and research category, and the research hotspots. From the publication of the first article in 2005 to 2021, the output and the number of citations of articles are on the rise. Based on the bibliometric analysis, we found that the current research focuses on the correlation between diagnosis (sensors and), treatment (oxidative stress, inflammation, and drug delivery) and safety (toxicity). Since 2019, research on nanomedicine and drug delivery has become a hotspot. So, more research in chemistry, materials, biology, and medicine is required to further develop and construct ROS-based nanomaterials.

Here, (-)-Tetrahydroalstonine (THA) was isolated from Alstonia scholaris and investigated for its neuroprotective effect towards oxygen–glucose deprivation/re-oxygenation (OGD/R)-induced neuronal damage. In this study, primary cortical neurons were pre-treated with THA and then subjected to OGD/R induction. The cell viability was tested by the MTT assay, and the states of the autophagy–lysosomal pathway and Akt/mTOR pathway were monitored by Western blot analysis. The findings suggested that THA administration increased the cell viability of OGD/R-induced cortical neurons. Autophagic activity and lysosomal dysfunction were found at the early stage of OGD/R, which were significantly ameliorated by THA treatment. Meanwhile, the protective effect of THA was significantly reversed by the lysosome inhibitor. Additionally, THA significantly activated the Akt/mTOR pathway, which was suppressed after OGD/R induction. In summary, THA exhibited promising protective effects against OGD/R-induced neuronal injury by autophagy regulation through the Akt/mTOR pathway.

ABSTRACT Cannulation through the femoral artery is the preferred method of establishing peripheral cardiopulmonary bypass in minimally invasive totally thoracoscopic cardiac surgery. However, faced with the contraindication of femoral artery cannulation, modified ascending aortic cannulation is an alternative approach to minimally invasive totally thoracoscopic cardiac surgery.

BackgroundRheumatic heart disease (RHD) accounts for a large proportion of Intensive Care Unit (ICU) deaths. Early prediction of RHD can help with timely and appropriate treatment to improve survival outcomes, and the XGBoost machine learning technology can be used to identify predictive factors; however, its use has been limited in the past. We compared the performance of logistic regression and XGBoost in predicting hospital mortality among patients with RHD from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database.MethodsThe patients with RHD in the MIMIC-IV database were divided into two groups retrospectively according to the availability of data and its clinical significance based on whether they survived or died. Backward stepwise regression was used to analyze the independent factors influencing patients with RHD, and to compare the differences between the two groups. The XGBoost algorithm and logistic regression were used to establish two prediction models, and the areas under the receiver operating characteristic curves (AUCs) and decision-curve analysis (DCA) were used to test and compare the models. Finally, DCA and the clinical impact curve (CIC) were used to validate the model.ResultsData on 1,634 patients with RHD were analyzed, comprising 207 who died during hospitalization and 1,427 survived. According to estimated results for the two models using AUCs [0.838 (95% confidence interval = 0.786–0.891) and 0.815 (95% confidence interval = 0.765–0.865)] and DCA, the logistic regression model performed better. DCA and CIC verified that the logistic regression model had convincing predictive value.ConclusionsWe used logistic regression analysis to establish a more meaningful prediction model for the final outcome of patients with RHD. This model might be clinically useful for patients with RHD and help clinicians to provide detailed treatments and precise management.

Immune system disorder is associated with metastasis of triple-negative breast cancers (TNBCs). A robust, individualized immune-related genes (IRGs)-based classifier was aimed to develop and validate in our study to precisely estimate the axillary lymph node (ALN) status preoperatively in patients with early-stage TNBC. We first analyzed RNA sequencing profiles in TNBC patients from The Cancer Genome Atlas database by using bioinformatics approaches, and screened 23 differentially expressed IRGs. A 9-gene panel was generated with an area under the curve (AUC) of 0.77 [95% confidence interval (95% CI), 0.68–0.87]. We detected the 9 ALN-status-related IRGs in the training set (n = 133) and developed a reduced and optimized five-IRGs signature, which effectively distinguished TNBC patients with ALN metastasis (AUC, 0.80; 95% CI, 0.65–0.86), and was superior to preoperative ultrasound-based ALN status (AUC, 0.73; 95% CI, 0.53–0.93). Predictive efficiency (AUC, 0.77; 95% CI 0.61–0.93) of this five-IRGs signature was validated in the validation set (n = 81). Furthermore, IRGs nomogram incorporated IRGs signature with US-based ALN status showed higher ALN status prediction efficacy than US-based ALN status and five-IRGs signature alone in both training and validation sets. IRGs nomogram may aid in identifying patients who can be exempted from axillary surgery.Novelty and impact: An immune-related genes (IRGs) nomogram was first developed and externally validated in our study, which incorporated the IRGs signature with ultrasound (US)-based axillary lymph nodes (ALN) status. IRGs nomogram is superior to IRGs signature alone for preoperative estimation of ALN metastasis in patients with triple-negative breast cancer (TNBC). It is a favourable biomarker for preoperatively predicting ALN metastasis risk and may aid in clinical decision-making in early-stage TNBCs.

Abstract Background We report the first successful short-term outcome of one-stage minimally invasive surgery (MIS) mitral valve repair and video-assisted thoracoscopic surgery (VATS) lobectomy. Case presentation We report the first successful short-term outcome of combined one-stage video-assisted thoracoscopic surgery lobectomy and minimally invasive surgery in a patient with operable primary right upper lobe adenocarcinoma and mitral regurgitation. Post- operative recovery was uneventful, and follow-up at 6 weeks confirmed an excellent surgical and oncologic outcome. Conclusions We think one-stage minimally invasive surgery (MIS) cardiac surgery and video-assisted thoracoscopic surgery (VATS) lobectomy would benefit patients with satisfactory cardiac and pulmonary function.

Objective. To analyze the therapeutic effects and organ rejection of anti-PD-1 immunotherapy or antivascular targeting therapy on patients with combined malignancies after organ transplantation. Methods. We collected retrospective studies on “post-transplantation, cancer, immunotherapy, and vascular targeting therapy” in Embase, Wanfang database, Cochrane Library, VIP databases, CNKI, and PubMed, and the case data were organized and analyzed. Results. Data from only 40 papers met our requirements, which included 2 literature reviews, 4 original researches, and 34 case reports from 2016 to 2020. A total of 40 studies involving 66 patients were included, who were divided into 3 groups (patients using CTLA-4 inhibitors, group 1; patients who received sequential or concurrent anti-PD-1 and anti-CTLA-4 therapy, group 2; and patients using PD-1/PD-L1 inhibitors, group 3). There was no statistical difference in patients’ DCR between the three groups (P>0.05). Also, compared with group 2, there was no statistically significant difference in recipient organ rejection in group 1 and group 3 (P>0.05). The DCR rate for antivascular targeted therapy is approximately 60%. Conclusions. Immunotherapy should be carefully selected for patients with combined malignancies after organ transplantation. Antivascular targeted therapy is one of the options worth considering; the risk of side effects of drug therapy is something that needs to be closely monitored when combined with immunotherapy.

Abstract Paravalvular leakage (PVL) after mitral valve replacement is a troublesome complication that may lead to severe symptoms and reoperation. Previous case reports on total thoracoscopic cardiac surgery without aortic cross-clamping for repairing late PVL are rare. We describe a 64-year-old man who had undergone aortic and mitral valve replacement via median sternotomy eight years earlier, and who recently developed cardiac failure due to severe tricuspid regurgitation (TR) and PVL in the posterior mitral annulus. During total thoracoscopic surgery with using the beating heart technique, direct closure of the PVL was achieved via pledgeted mattress sutures, and tricuspid valvuloplasty was routinely performed to treat TR. This case indicated that total thoracoscopic surgery on a beating heart may be an excellent option for treating PVL concomitant with TR.

Background. Marfan syndrome (MFS) is a connective tissue disease involving multiple systems, with thoracic aortic aneurysm (TAA) as the most common life-threatening manifestation. Method. A pedigree with TAA was investigated, and peripheral venous blood was extracted from six family members. After whole exome sequencing (WES) and chromosomal microarray analysis (CMA) in these individuals, bioinformatics and inheritance analyses were performed. Result. WES revealed a novel, small, 0.76 Mb microdeletion in 15q21.1, which cosegregated with the disease phenotype in the family and led to the haploinsufficiency of the fibrillin 1 (FBN1) gene, which is associated with MFS. This small copy number variant (CNV) was confirmed by CMA. Conclusion. Our study expands the phenotypic spectrum of the pathogenic CNV associated with MFS, thereby facilitating clinical genetic diagnosis and future genetic counseling for this family.

Heart failure is induced by multiple pathological mechanisms, and current therapies are ineffective against heart failure with preserved ejection fraction (HFpEF). As there are limited animal models of HFpEF, its underlying mechanisms have not yet been elucidated. Here, we employed the descending aortic constriction (DAC) technique to induce chronic pressure overload in the left ventricles of Tibetan minipigs for 12 weeks. Cardiac function, pathological and cellular changes, fibrotic signaling activation, and gene expression profiles were explored. The left ventricles developed concentric hypertrophy from weeks 4 to 6 and transition to dilation starting in week 10. Notably, the left ventricular ejection fraction was maintained at >50% in the DAC group during the 12-week period. Pathological examination, biochemical analyses, and gene profile analysis revealed evidence of inflammation, fibrosis, cell death, and myofilament dephosphorylation in the myocardium of HFpEF model animals, together with gene expression shifts promoting cardiac remodeling and downregulating metabolic pathways. Furthermore, we noted the activation of several signaling proteins that impact cardiac fibrosis and remodeling, including transforming growth factor-β/SMAD family members 2/3, type I/III/V collagens, phosphatidylinositol 3-kinase, extracellular signal-regulated kinase, matrix metalloproteinases 2 and 9, tissue inhibitor of metalloproteinases 1 and 2, interleukins 6 and 1β, and inhibitor of κBα/nuclear factor-κB. Our findings demonstrate that this chronic pressure overload-induced porcine HFpEF model is a powerful tool to elucidate the mechanisms of this disease and translate preclinical findings.

Abstract Background The totally thoracoscopic procedure for mitral valve (MV) disease is a minimally invasive method. We investigated the procedure’s feasibility, safety and effectiveness when it was performed by an experienced operator. Methods We retrospectively analysed 53 consecutive patients with MV disease treated between December 2014 and April 2017 by minimally invasive procedures. The procedures were performed on femoral artery-vein bypass through three 2–4 cm incisions, with one additional penetrating point on the right chest wall under totally thoracoscopic visual guidance and surveillance of transoesophageal echocardiography. Results Two patients who underwent intraoperative conversion to sternotomy were excluded due to indivisible pleural cavity adhesion. Of the others (38 female patients, average age, 49 ± 14 years, left ventricular ejection fraction, 59 ± 7%), 34 received MV replacement for rheumatic mitral lesions, which was redone for one patient after the discovery of serious paravalvular leakage, 17 received MV repair for mitral regurgitation (with 4 secondary to atrial septum defect, 2 diagnosed with left atrial myxoma, and 2 redone for mitral valve replacement due to repair failure), 28 received additional tricuspid valvuloplasty, and one patient received a Warden procedure. The cardiopulmonary bypass and aortic cross clamp times were 144 ± 39 min and 80 ± 22 min, respectively. Postoperational chest tube drainage in the first 48 h was 346 ± 316 ml. The ventilation time and intensive care unit stay length were 11 ± 11 h and 23 ± 2 h, respectively. One patient died of disseminated intravascular coagulation and prosthesis thrombosis with fear of anticoagulation-related bleeding. Conclusions The totally thoracoscopic procedure on mitral valves by an experienced surgeon is technically feasible, safe, effective and worthy of widespread adoption in clinical practice.

Abstract Polyploidy in plants can bestow long-term evolutionary flexibility and resistance to biotic and abiotic stresses. The upstream activation mechanisms of salt response remain unknown. Here we integrated transcriptome, miRNA and proteome data to describe the link between abscisic acid (ABA)-effectors and salt resistance against the background of Paulownia genome. Combing GO and KEGG pathway annotation of differentially expressed genes and proteins, as well as differentially expressed miRNA, these results reflect endogenous signal ABA activate the downstream effectors, such as ion channel effectors and oxido-reduction effectors, to maintain the homeostasis of Paulownia’s growth. The cascaded metabolic network involved ABA biosynthesis, signaling transduction and the response of effectors. Our results will contribute to a comprehensive understanding of the genetic basis of salt tolerance, which may help to expand the available arable land for P. fortunei cultivation.

Paulownia fortunei is an ecologically and economically important tree species that is widely used as timber and chemical pulp. Its autotetraploid, which carries a number of valuable traits, was successfully induced with colchicine. To identify differences in gene expression between P. fortunei and its synthesized autotetraploid, we performed transcriptome sequencing using an Illumina Genome Analyzer IIx (GAIIx). About 94.8 million reads were generated and assembled into 383,056 transcripts, including 18,984 transcripts with a complete open reading frame. A conducted Basic Local Alignment Search Tool (BLAST) search indicated that 16,004 complete transcripts had significant hits in the National Center for Biotechnology Information (NCBI) non-redundant database. The complete transcripts were given functional assignments using three public protein databases. One thousand one hundred fifty eight differentially expressed complete transcripts were screened through a digital abundance analysis, including transcripts involved in energy metabolism and epigenetic regulation. Finally, the expression levels of several transcripts were confirmed by quantitative real-time PCR. Our results suggested that polyploidization caused epigenetic-related changes, which subsequently resulted in gene expression variation between diploid and autotetraploid P. fortunei. This might be the main mechanism affected by the polyploidization. Our results represent an extensive survey of the P. fortunei transcriptome and will facilitate subsequent functional genomics research in P. fortunei. Moreover, the gene expression profiles of P. fortunei and its autopolyploid will provide a valuable resource for the study of polyploidization.

Three strategies using lamivudine have been proposed to prevent chemotherapy-induced HBV (hepatitis B virus) reactivation in the clinical setting. The purpose of this meta-analysis is to evaluate the efficacy of the early preemptive strategy, deferred preemptive strategy and therapeutic strategy in patients with HBsAg-positive breast cancer during chemotherapy.Clinical studies published from database inception until Nov 1, 2014, were included for analysis. The primary outcomes were overall survival, rate of chemotherapy disruption and virological and clinical reactivation. The secondary outcomes were the rates of HBV-related chemotherapy disruption, HBV-related mortality, YMDD mutations and withdrawal hepatitis.Four hundred and thirty patients in four studies that compared the early preemptive strategy with a therapeutic strategy were included. Application of early preemptive lamivudine was superior in reducing HBV recurrence (pooled OR: 0.12, 95% CI, 0.04 to 0.31, P< 0.0001), the incidence of HBV-related hepatitis (pooled OR: 0.13, 95% CI, 0.04 to 0.37, P< 0.0001) and the rate of chemotherapy disruption (pooled OR: 0.37, 95% CI, 0.23 to 0.60, P< 0.0001). In these two groups, no significant difference was found in overall mortality (P = 0.32), YMDD mutant rate (P = 0.13) or incidence of withdrawal hepatitis (P = 0.38). Of the two studies that compared the efficacy of an early and a deferred preemptive strategy, one showed that an early preemptive strategy significantly reduced the incidence of hepatitis (P = 0.046), whereas the other showed no significant difference (P = 0.7).An early preemptive strategy is superior to a therapeutic strategy in decreasing the incidence of HBV reactivation, incidence of HBV-related hepatitis and rate of chemotherapy disruption in patients with breast cancer. A deferred preemptive strategy might be an alternative approach to controlling viral replication.

Purpose: To study the influence of miR-216b expression in breast cancer (BC), and the underlying mechanism(s) of action. Methods: Viability of BC cell lines was determined using CCK-8 as well as colony formation assays, while the abundance of mRNAs of key genes was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blot assay was utilized to measure protein expressions of E2F4 and stem cell markers. Bioinformatics and dual-luciferase procedures were deployed to predict the targets of miR-216b on 3'-UTR of E2F4. Results: MiR-216b was reduced in BC tissues and mammary carcinoma cell line, MCF-7, relative to those in paracancerous tissue and normal breast cell line, MCF-10A (p < 0.05). Compared with miR-NC group, cell viability, median inhibitory concentration (IC50), and potential to form colonies in cisplatin-insensitive cell line MCF-7/DDP were reduced by miR-216b. Moreover, MiR-216b suppressed stem cell characteristics and decreased the expressions of ALDH1 and Oct-4 in BC cells. Inhibition of miR-216b resulted in significant increase in microsphere formation and expressions of ALDH1 and Oct-4, when compared with NC-inhibitor group. In addition, E2F transcription factor 4 (E2F4) was identified as the downstream gene of miR-216b. Knockdown of E2F4 annulled the influence of miR-216b on insensitivity to cisplatin and stem cell likeness of MCF-7/DDP. Conclusion: MiR-216b induces increase in BC response to cisplatin and suppressed stem cell characteristics by regulating E2F4. This finding may be useful for developing strategies aimed at reversing cisplatin insensitivity in BC. [ABSTRACT FROM AUTHOR]