Fractal analysis of left ventricular trabeculae in post-STEMI: from acute to chronic phase.

PURPOSE: The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). METHODS: This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7 days), subacute (1 month after pPCI), and chronic phases (6 months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. RESULTS: Among the 200 analyzed patients (182 men; median age, 61 years; age range, 50-66 years), 37 (18.5%) encountered MACE during a median follow-up of 31.2 months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk. CONCLUSION: In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow. CRITICAL RELEVANCE STATEMENT: In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event. KEY POINTS: • Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE. • Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors. • Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.

Prediction model based on MRI morphological features for distinguishing benign and malignant thyroid nodules.

BACKGROUND: The low specificity of Thyroid Imaging Reporting and Data System (TI-RADS) for preoperative benign-malignant diagnosis leads to a large number of unnecessary biopsies. This study developed and validated a predictive model based on MRI morphological features to improve the specificity. METHODS: A retrospective analysis was conducted on 825 thyroid nodules pathologically confirmed postoperatively. Univariate and multivariate logistic regression were used to obtain ß coefficients, construct predictive models and nomogram incorporating MRI morphological features in the training cohort, and validated in the validation cohort. The discrimination, calibration, and decision curve analysis of the nomogram were performed. The diagnosis efficacy, area under the curve (AUC) and net reclassification index (NRI) were calculated and compared with TI-RADS. RESULTS: 572 thyroid nodules were included (training cohort: n = 397, validation cohort: n = 175). Age, low signal intensity on T2WI, restricted diffusion, reversed halo sign in delay phase, cystic degeneration and wash-out pattern were independent predictors of malignancy. The nomogram demonstrated good discrimination and calibration both in the training cohort (AUC = 0.972) and the validation cohort (AUC = 0.968). The accuracy, sensitivity, specificity, PPV, NPV and AUC of MRI-based prediction were 94.4%, 96.0%, 93.4%, 89.9%, 96.5% and 0.947, respectively. The MRI-based prediction model exhibited enhanced accuracy (NRI>0) in comparison to TI-RADSs. CONCLUSIONS: The prediction model for diagnosis of benign and malignant thyroid nodules demonstrated a more notable diagnostic efficacy than TI-RADS. Compared with the TI-RADSs, predictive model had better specificity along with a high sensitivity and can reduce overdiagnosis and unnecessary biopsies.

Prognostic value of right atrial strains in arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty infiltration of atrial and ventricular myocardium resulting in adverse cardiac events. Atrial function has been increasingly recognized as prognostically important for cardiovascular disease. As the right atrial (RA) strain is a sensitive parameter to describe RA function, we aimed to analyze the prognostic value of the RA strain in ARVC. METHODS: RA strain parameters were derived from cardiac magnetic resonance (CMR) images of 105 participants with definite ARVC. The endpoint was defined as a combination of sudden cardiac death, survival cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. Cox regression and Kaplan-Meier survival analyses were performed to evaluate the association between RA strain parameters and endpoint. Concordance index (C index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the incremental value of RA strain in predicting the endpoint. RESULTS: After a median follow-up of 5 years, 36 (34.3%) reaching the endpoint displayed significantly reduced RA strain parameters. At Kaplan-Meier analysis, impaired RA reservoir (RARS) and booster strains (RABS) were associated with an increased risk of the endpoint. After adjusting for conventional risk factors, RARS (hazard ratio [HR], 0.956; p = 0.005) and RABS (HR, 0.906; p = 0.002) resulted as independent predictors for endpoint at Cox regression analyses. In addition, RARS and RABS improved prognostic value to clinical risk factors and CMR morphological and functional predictors (all p < 0.05). CONCLUSION: RARS and RABS were independent predictors for adverse cardiac events, which could provide incremental prognostic value for conventional predictors in ARVC. CRITICAL RELEVANCE STATEMENT: We evaluated the prognostic value of right atrial strain in ARVC patients and suggested cardiologists consider RA strain as a predictive parameter when evaluating the long-term outcome of ARVC patients in order to formulate better clinical therapy. KEY POINTS: • Patients with ARVC had significantly reduced RA strain and strain rates compared with healthy participants. • Participants with lower RA reservoir and booster stains were associated with a significantly higher risk of adverse cardiac events. • RA booster and reservoir strain provide incremental value to conventional parameters.

Nomogram Utilizing ABVS Radiomics and Clinical Factors for Predicting ≤ 3 Positive Axillary Lymph Nodes in HR+ /HER2- Breast Cancer with 1-2 Positive Sentinel Nodes.

BACKGROUND: In HR+ /HER2- breast cancer patients with ≤ 3 positive axillary lymph nodes (ALNs), genomic tests can streamline chemotherapy decisions. Current studies, centered on tumor metrics, miss broader patient insights. Automated Breast Volume Scanning (ABVS) provides advanced 3D imaging, and its potential synergy with radiomics for ALN evaluation is untapped. OBJECTIVE: This study sought to combine ABVS radiomics and clinical characteristics in a nomogram to predict ≤ 3 positive ALNs in HR+ /HER2- breast cancer patients with 1-2 positive sentinel lymph nodes (SLNs), guiding clinicians in genetic test candidate selection. METHODS: We enrolled 511 early-stage breast cancer patients: 362 from A Hospital for training and 149 from B Hospital for validation. Using LASSO logistic regression, primary features were identified. A clinical-radiomics nomogram was developed to predict the likelihood of ≤ 3 positive ALNs in HR+ /HER2- patients with 1-2 positive SLNs. We assessed the discriminative capability of the nomogram using the ROC curve. The model's calibration was confirmed through a calibration curve, while its fit was evaluated using the Hosmer-Lemeshow (HL) test. To determine the clinical net benefits, we employed the Decision Curve Analysis (DCA). RESULTS: In the training group, 81.2% patients had ≤ 3 metastatic ALNs, and 83.2% in the validation group. We developed a clinical-radiomics nomogram by analyzing clinical characteristics and rad-scores. Factors like positive SLNs (OR=0.077), absence of negative SLNs (OR=11.138), lymphovascular invasion (OR=0.248), and rad-score (OR=0.003) significantly correlated with ≤ 3 positive ALNs. The clinical-radiomics nomogram, with an AUC of 0.910 in training and 0.882 in validation, outperformed the rad-score-free clinical nomogram (AUCs of 0.796 and 0.782). Calibration curves and the HL test (P values 0.688 and 0.691) confirmed its robustness. DCA showed the clinical-radiomics nomogram provided superior net benefits in predicting ALN burden across specific threshold probabilities. CONCLUSION: We developed a clinical-radiomics nomogram that integrated radiomics from ABVS images and clinical data to predict the presence of ≤ 3 positive ALNs in HR+ /HER2- patients with 1-2 positive SLNs, aiding oncologists in identifying candidates for genomic tests, bypassing ALND. In the era of precision medicine, combining genomic tests with SLN biopsy refines both surgical and systemic patient treatments.

Prognostic value of right ventricular trabecular complexity in patients with arrhythmogenic cardiomyopathy.

OBJECTIVES: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM). METHODS: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD. RESULTS: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X2 = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045). CONCLUSIONS: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value. CLINICAL RELEVANCE STATEMENT: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM. KEY POINTS: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM.

Quantitative evaluation of diffusion-weighted MRI for differentiating benign and malignant thyroid nodules larger than 4 cm.

PURPOSE: Our study aimed to diagnose benign or malignant thyroid nodules larger than 4 cm using quantitative diffusion-weighted imaging (DWI) analysis. METHODS: Eighty-two thyroid nodules were investigated retrospectively and divided them into benign (n = 62) and malignant groups (n = 20). We calculated quantitative features DWI and apparent diffusion coefficient (ADC) signal intensity standard deviation (DWISD and ADCSD), DWI and ADC signal intensity ratio (DWISIR and ADCSIR), mean ADC and minimum ADC value (ADCmean and ADCmin) and ADC value standard deviation (ADCVSD). Univariate and multivariate logistic regression were conducted to identify independent predictors, and develop a prediction model. We performed receiver operating characteristic (ROC) analysis to determine the optimal threshold of risk factors, and constructed combined threshold models. Our study calculated diagnostic performance including area under the ROC curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and unnecessary biopsy rate of all models were calculated and compared them with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS) result. RESULTS: Two independent predictors of malignant nodules were identified by multivariate analysis: DWISIR (P = 0.007) and ADCmin (P < 0.001). The AUCs for multivariate prediction model, combined DWISIR and ADCmin thresholds model, combined DWISIR and ADCSIR thresholds model and ACR-TIRADS were 0.946 (0.896-0.996), 0.875 (0.759-0.991), 0.777 (0.648-0.907) and 0.722 (0.588-0.857). The combined DWISIR and ADCmin threshold model had the lowest unnecessary biopsy rate of 0%, compared with 56.3% for ACR-TIRADS. CONCLUSION: Quantitative DWI demonstrated favorable malignant thyroid nodule diagnostic efficacy. The combined DWISIR and ADCmin thresholds model significantly reduced the unnecessary biopsy rate.

Preoperative Cervical Lymph Node Metastasis Prediction in Papillary Thyroid Carcinoma: A Noninvasive Clinical Multimodal Radiomics (CMR) Nomogram Analysis.

This study aimed to evaluate the feasibility of applying a clinical multimodal radiomics nomogram based on ultrasonography (US) and multiparametric magnetic resonance imaging (MRI) for the prediction of cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) preoperatively. We performed retrospective evaluations of 133 patients with pathologically confirmed PTC, who were assigned to the training cohort and validation cohort (7 : 3), and extracted radiomics features from the preoperative US, T2-weighted (T2WI),diffusion-weighted (DWI), and contrast-enhanced T1-weighted (CE-T1WI) images. Optimal subsets were selected using minimum redundancy, maximum relevance, and recursive feature elimination in the support vector machine (SVM). For LNM prediction, the radiomics model was constructed by SVM, and Multi-Omics Graph cOnvolutional NETworks (MOGONET) was used for the effective classification of multiradiomics data. Multivariable logistic regression incorporating multiradiomics signatures and clinical risk factors was used to generate a nomogram, whose performance and clinical utility were assessed. Results showed that the nine most predictive features were separately selected from US, T2WI, DWI, and CE-T1WI images, and 18 features were selected in the combined model. The combined radiomics model showed better performance than models based on US, T2WI, DWI, and CE-T1WI. In a comparison of the combined radiomics and MOGONET model, receiver operating curve analysis showed that the area under the curve (AUC) value (95% CI) was 0.84 (0.76-0.93) and 0.84 (0.71-0.96) for the MOGONET model in the training and validation cohorts, respectively. The corresponding values (95% CI) for the combined radiomics model were 0.82 (0.74-0.90) and 0.77 (0.61-0.94), respectively. The MOGONET model had better performance and better prediction specificity compared with the combined radiomics model. The nomogram including the MOGONET signature showed a better predictive value (AUC: 0.81 vs. 0.88) in the training and validation (AUC: 0.74vs. 0.87) cohorts, as compared with the clinical model. Calibration curves showed good agreement in both cohorts. The applicability of the clinical multimodal radiomics (CMR) nomogram in clinical settings was validated by decision curve analysis. In patients with PTC, the CMR nomogram could improve the prediction of cervical LNM preoperatively and may be helpful in clinical decision-making.

MRI-Based Texture Analysis for Preoperative Prediction of BRAF V600E Mutation in Papillary Thyroid Carcinoma.

Purpose: BRAF V600E mutation can compensate for the low detection rate by fine-needle aspiration (FNA) and is related to aggressiveness and lymph node metastasis. This study aimed to investigate the relationship between texture analysis features based on magnetic resonance imaging (MRI) and mutations. Methods: Retrospective analysis was performed on patients with postoperative pathology confirmed papillary thyroid carcinoma (PTC) from 2017 to 2021. One thousand one hundred and thirty-two texture features were extracted from T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) separately by outlining the tumor volume of interest (VOI). Univariate, minimum redundancy maximum relevance (mRMR), and multivariate analyses were used for feature selection to construct 3 models (T2WI, CE-T1WI, and combined model) to predict mutation. The reproducibility between observers was evaluated by intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) analysis was used to assess the performance of models. The diagnostic performance of the optimal cut-off value of models were calculated and validated by 10-fold cross-validation. Results: A total of 80 PTCs (22 BRAF V600E wild-type and 58 BRAF V600E mutant) were included in our study. Good interobserver agreement was found on texture features we selected (all ICCs >0.75). The area under the ROC curves (AUCs) for the T2WI model, CE-T1WI model, and combined model were 0.83 (95% CI: 0.75-0.91), 0.83 (95% CI: 0.73-0.90), and 0.88 (95% CI: 0.81-0.94), respectively. The accuracy, sensitivity, specificity, PPV, and NPV were 0.776, 0.679, 0.905, 0.905, and 0.679 for the T2WI model at a cut-off value of 0.674; 0.755, 0.750, 0.762, 0.808, and 0.696 for the CE-T1WI model at a cut-off value of 0.573; 0.816, 0.893, 0.714, 0.806, and 0.833 for the combined model at a cut-off value of 0.420. Conclusion: MRI-based texture analysis could be a potential method for predicting BRAF V600E mutation in PTC preoperatively.

Myocardial extracellular volume quantified by cardiac magnetic resonance predicts left ventricular aneurysm following acute myocardial infarction.

OBJECTIVE: This study aimed to investigate the correlation between increased extracellular matrix estimated by cardiac magnetic resonance (CMR) and left ventricular aneurysm after acute myocardial infarction. METHODS: A total of 175 patients from 3 centers with an isolated left anterior descending culprit vessel underwent CMR examinations within 1 week and at a 6-month follow-up. Of these, 92 were identified to have left ventricular aneurysms (LVAs): 74 with functional aneurysm and 18 with anatomical aneurysm. The predictive significance of acute extracellular volume (ECV), left gadolinium enhancement (LGE), and other characteristics were analyzed using binary logistic regression analysis. RESULTS: Patients with LVA were more likely to present with left ventricular adverse remodeling (LVAR) than those without (p = 0.009). With optimal cutoff values of 30.90% for LGE and 33% for ECV to discriminate LVA from non-LVA, the area under the curve (AUC) by receiver operator characteristic curve (ROC) analysis was 0.92 (95% CI: 0.87-0.96; p < 0.001) and 0.93 (95% CI: 0.88-0.96; p < 0.001), respectively. ECV was significantly better than LGE at discriminating between functional and anatomical LVA (p < 0.001). Both acute LGE and ECV were predictors of LVA, with an odds ratio of 1.35 (95% CI: 1.21-1.52, p < 0.001) and 1.23 (95% CI: 1.13-1.33, p < 0.001), respectively, by multivariable logistic regression analysis. CONCLUSIONS: Acute LGE and ECV of the myocardium provided predictive significance for LVA. The discriminative significance of ECV for functional versus anatomical LVA was better than the discriminative significance of LGE. KEY POINTS: • Patients with LVA were more likely to present with LVAR. • Acute LGE and ECV of the myocardium provided the strongest predictive significance for LVA. • The discriminative significance of ECV for functional versus anatomical LVA was better than that of LGE.

A Radiomic MRI based Nomogram for Prediction of Heart Failure with Preserved Ejection Fraction in Systemic Lupus Erythematosus Patients: Insights From a Three-Center Prospective Study.

BACKGROUND: Myocardial T1 and extracellular volume (ECV) fraction values have important roles in the prognostication of heart failure with preserved ejection fraction (HFpEF). However, the traditional mean quantification of intensity levels is not sufficient. PURPOSE: To evaluate a T1 map-based radiomic nomogram as a long-term prognosticator for HFpEF in systemic lupus erythematosus (SLE) patients. STUDY TYPE: Prospective. POPULATION: A total of 115 SLE patients and 50 age- and gender-matched controls. FIELD STRENGTH/SEQUENCE: A 3.0 T scanner; cine imaging, precontrast and post-contrast T1 mapping and T2 mapping sequences. ASSESSMENT: A radiomic nomogram was developed based on precontrast T1 mapping. Three independent readers assessed and compared the ECV value and the value of the radiomic nomogram for predicting HFpEF in SLE patients. STATISTICAL TEST: Cox proportional hazard models, Youden index for determining cut-off values for high HFpEF risk vs. low HFpEF risk classification, Kaplan-Meier analysis, intraclass correlation (ICC), and Uno C statistic test. RESULTS: During a median follow-up of 27 (interquartile range, 19-37) months, 31 SLE patients developed HFpEF. Patients with elevated ECV (≥31%) and a higher output (≥42.7) from the radiomic feature "S_33_sum average" of the precontrast T1 map had a significantly higher risk of developing HFpEF than those who had lower ECV (<31%) and an output <42.7. Patients with a higher "S_33_sum average" value on precontrast T1 map had a significantly increased risk for HFpEF (hazard ratio, 1.363, 95% CI, 1.130-1.645), after adjusting for covariates including ECV and LVEF. Finally, "S_33_sum average" from precontrast T1 mapping had modest but significantly incremental prognostic value over the mean ECV value (Uno C statistic comparing models, 0.860 vs. 0.835). DATA CONCLUSION: The precontrast T1 map-based radiomic nomogram, as a measure of diffuse myocardial fibrosis was associated with HFpEF and provided modest prognostic value for predicting HFpEF in SLE patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Downregulation of PDGF-D Inhibits Proliferation and Invasion in Breast Cancer MDA-MB-231 Cells.

BACKGROUND: The platelet derived growth factor-D (PDGF-D) plays an important role in breast tumor aggressiveness. However, limited study has investigated the effect of silencing PDGF-D on the biological function of breast cancer. The purpose of this study is to clarify the potential value of PDGF-D as a target for breast cancer treatment. METHODS: Reverse transcription-polymerase chain reaction and western blot were used to detect PDGF-D expression in 5 different breast cancer cells. The lentiviral vector was usd to silence PDGF-D in MDA-MB-231 cells. Then, Methyl Thiazolyl Tetrazolium was used to detect cell viability, 5-Ethynyl-2'- deoxyuridine and a soft agar assay were used to detect cell proliferation and clonality. Additionally, cell apoptosis after PDGF-D knockdown was measured by Annexin V/ Prodium Iodide staining, and cell migration was detected by trans-well assay. Survival rate and tumor size were measured by nude mice transplantation. RESULTS: The MDA-MB-231 and SK-BR-3 cell lines showed higher PDGF-D expression than the MCF7 cell lines (P<.05). After the PDGF-D gene was silenced, the growth and colony forming abilitys ignificantly decreased (P<.05) together with the induction of apoptosis in MDA-MB-231 cells (P<.05). Moreover, MDA-MB-231 cells with PDGF-D silencing showed significantly diminished aggressive migration and invasion potential compared to other cells (P<.05). In vivo experiments also indicated that PDGF-D silencing inhibited tumor growth and improved the survival rate of tumor-bearing mice. CONCLUSION: Downregulation of PDGF-D had dramatic effects on breast cancer cell proliferation, apoptosis and migration, which indicates that it plays an important role in breast cancer development and progression.

Evolving Fully Automated Machine Learning via Life-Long Knowledge Anchors.

Automated machine learning (AutoML) has achieved remarkable progress on various tasks, which is attributed to its minimal involvement of manual feature and model designs. However, most of existing AutoML pipelines only touch parts of the full machine learning pipeline, e.g., neural architecture search or optimizer selection. This leaves potentially important components such as data cleaning and model ensemble out of the optimization, and still results in considerable human involvement and suboptimal performance. The main challenges lie in the huge search space assembling all possibilities over all components, as well as the generalization ability over different tasks like image, text, and tabular etc. In this paper, we present a first-of-its-kind fully AutoML pipeline, to comprehensively automate data preprocessing, feature engineering, model generation/selection/training and ensemble for an arbitrary dataset and evaluation metric. Our innovation lies in the comprehensive scope of a learning pipeline, with a novel "life-long" knowledge anchor design to fundamentally accelerate the search over the full search space. Such knowledge anchors record detailed information of pipelines and integrates them with an evolutionary algorithm for joint optimization across components. Experiments demonstrate that the result pipeline achieves state-of-the-art performance on multiple datasets and modalities. Specifically, the proposed framework was extensively evaluated in the NeurIPS 2019 AutoDL challenge, and won the only champion with a significant gap against other approaches, on all the image, video, speech, text and tabular tracks.

microRNA-377 acts as a suppressor in esophageal squamous cell carcinoma through CBX3-dependent P53/P21 pathway.

Stem cells play pivotal roles in esophageal squamous cell carcinoma (ESCC) recurrence and metastasis. The self-renewal ability of stem cells was associated with specific microRNAs (miRs). Herein, we identified the effects of miR-377 on ESCC stem cell activities. First, the expression of miR-377 in ESCC and adjacent normal tissues was determined. The relationship between miR-377 and chromobox protein homolog 3 (CBX3) was assessed by a dual-luciferase reporter gene assay. miR-377 was overexpressed or inhibited in ESCC stem cells to explore its role in ESCC. To further investigate the mechanism of miR-377 in ESCC, cells were introduced with short hairpin RNA against CBX3 or pifithrin-α (inhibitor of P53 pathway). Besides, the expression of P21, P53, CD133, CD13, Nanog, sex determining region Y-Box 2 (Sox2), and octamer-binding transcription factor 4 (Oct4), cell sphere formation, colony formation, and proliferation were evaluated respectively. Finally, limiting dilution assay in vivo and tumor xenograft in nude mice were conducted to confirm the roles of miR-377 in vivo. miR-377 was poorly expressed in ESCC. Overexpression of miR-377 could suppress the stem-like trait of ESCC as well as the tumor growth in vivo. miR-377 targeted CBX3 to activate the P53/P21 pathway. Besides, the expression of stem-like markers including CD133, CD13, Oct4, Sox2, and Nanog was decreased, and the abilities of cell sphere formation, colony formation, proliferation, and tumorigenicity were significantly reduced by overexpressing miR-377 or silencing CBX3. The results were reversed after inactivating the P53/P21 pathway. In summary, upregulation of miR-377 inhibits the self-renewal of ESCC stem cells by inhibiting CBX3 expression and promoting activation of the P53/P21 pathway.

Hypoxic bone marrow mesenchymal cell-extracellular vesicles containing miR-328-3p promote lung cancer progression via the NF2-mediated Hippo axis.

Lung cancer is the most aggressive tumour afflicting patients on a global scale. Extracellular vesicle (EV)-delivered microRNAs (miRs) have been reported to play critical roles in cancer development. The current study aimed to investigate the role of hypoxic bone marrow mesenchymal cell (BMSC)-derived EVs containing miR-328-3p in lung cancer. miR-328-3p expression was determined in a set of lung cancer tissues by RT-qPCR. BMSCs were infected with lentivirus-mediated miR-328-3p knock-down and then cultured in normoxic or hypoxic conditions, followed by isolation of EVs. Following ectopic expression and depletion experiments in lung cancer cells, the biological functions of miR-328-3p were analysed using CCK-8 assay, flow cytometry and Transwell assay. Xenograft in nude mice was performed to test the in vivo effects of miR-328-3p delivered by hypoxic BMSC-derived EVs on tumour growth of lung cancer. Finally, the expression of circulating miR-328-3p was detected in the serum of lung cancer patients. miR-328-3p was highly expressed in EVs derived from hypoxic BMSCs. miR-328-3p was delivered to lung cancer cells by hypoxic BMSC-derived EVs, thereby promoting lung cancer cell proliferation, invasion, migration and epithelial-mesenchymal transition. miR-328-3p targeted NF2 to inactivate the Hippo pathway. Moreover, EV-delivered miR-328-3p increased tumour growth in vivo. Additionally, circulating miR-328-3p was bioactive in the serum of lung cancer patients. Taken together, our results demonstrated that hypoxic BMSC-derived EVs could deliver miR-328-3p to lung cancer cells and that miR-328-3p targets the NF2 gene, thereby inhibiting the Hippo pathway to ultimately promote the occurrence and progression of lung cancer.

Effects of Blast Wave-induced Biomechanical Changes on Lung Injury in Rats.

OBJECTIVE: To observe the dynamic impacts of shock waves on the severity of lung injury in rats with different injury distances. METHODS: Simulate open-field shock waves; detect the biomechanical effects of explosion sources at distances of 40, 44, and 48 cm from rats; and examine the changes in the gross anatomy of the lungs, lung wet/dry weight ratio, hemoglobin concentration, blood gas analysis, and pathology. RESULTS: Biomechanical parameters such as the overpressure peak and impulse were gradually attenuated with an increase in the injury distance. The lung tissue hemorrhage, edema, oxygenation index, and pathology changed more significantly for the 40 cm group than for the 44 and 48 cm groups. The overpressure peak and impulse were significantly higher for the 40 cm group than for the 44 and 48 cm groups ( P < 0.05 or P < 0.01). The animal mortality was significantly higher for the 40 cm group than for the other two groups (41.2% vs. 17.8% and 10.0%, P < 0.05). The healing time of injured lung tissues for the 40 cm group was longer than those for the 44 and 48 cm groups. CONCLUSIONS: The effects of simulated open-field shock waves on the severity of lung injuries in rats were correlated with the injury distances, the peak overpressure, and the overpressure impulse.

[Clinical effect of Liyan Tongqiao acupuncture in treatment of post-stroke dysphagia: an analysis based on diffusion tensor imaging].

OBJECTIVE: To investigate the clinical change of post-stroke dysphagia after the intervention of Liyan Tongqiao （relieving sore-throat and dredging orifices）acupuncture using cranial diffusion tensor imaging (DTI). METHODS: A total of 60 patients with post-stroke dysphagia were enrolled and randomly divided into Liyan Tongqiao acupuncture group and neurology treatment group, with 30 patients in each group. The patients in the neurology treatment group were given routine neurology treatment and swallowing rehabilitation training, and those in the Liyan Tongqiao acupuncture group received acupuncture at Sishencong (EX-HN1), Baihui (GV20), bilateral Tai-yang (EX-HN5), and bilateral Fengchi (GB20) and tongue triple acupuncture, with an electroacupuncture apparatus for EX-HN1, bilateral GB20, and tongue triple acupuncture, for a needle retaining time of 30 minutes each time, once a day and 5 times a week, in addition to the treatment in the neurology treatment group. Each course of treatment was 3 weeks, and both groups were treated for 2 courses. Swallowing function assessment and cranial DTI were performed after treatment. RESULTS: After 6 weeks of treatment, both groups had a marked improvement in swallowing function, a significantly greater change in video fluoroscopic swallowing study (VFSS) score and a higher mean FA value (P<0.05). Compared with the neurology treatment group, the Liyan Tongqiao acupuncture group had a marked improvement in swallowing function, a significantly greater change in VFSS score in the pharyngeal phase and a higher mean FA value (P<0.05). CONCLUSION: Liyan Tongqiao acupuncture can improve dysphagia and swallowing function in the pharyngeal phase in VFSS, possibly by promoting the remodeling of cerebral cortex and increasing the FA value of infarct zone through the stimulation of related acupoint signals.

Thoracic tumor resection combined with SVC replacement using autologous pericardium.

BACKGROUND: Invasion of the superior vena cava (SVC) by thoracic tumors and occurrence of SVC syndrome are often encountered in clinical practice; but the prognosis in these cases is poor. Replacement of the SVC with autologous pericardial tissue is rarely performed. In this study, we sought to investigate the postoperative outcomes of this rare procedure. METHODS: We performed a retrospective analysis of six patients who underwent SVC replacement using autologous pericardial tissue between October 2010 and November 2016. We collected data on the patients' pathological features, operative characteristics, postoperative outcomes, and survival. RESULTS: All six patients were male with an average age of 52 years (range, 18-62 years). Three of the patients had lung cancer, one had stage III thymoma, and two had germinoma. Four of the six patients had mild or moderate superior vena cava compression and no corresponding clinical symptoms. The other two patients had severe compression and obvious symptoms of SVC syndrome, with the typical swelling of the face, eyelids, and upper extremities. All six patients underwent complete tumor resection, with two of the lung cancer patients undergoing right lobectomy and one undergoing right pneumonectomy. With respect to the postoperative outcomes, one patient died, whereas the others did not develop any major complications. At the end of the follow-up period, five of the patients were alive and none of the patients had developed thrombosis in the grafts. CONCLUSIONS: Our findings indicated that SVC replacement with autologous pericardium is technically feasible and safe, with few postoperative complications and favorable long-term effects. Although it has some limitations, this method appears to be useful in achieving SVC reconstruction of moderate size. SVC replacement with autologous pericardium appears to have the potential for widespread clinical use.

Interaction of MCM7 and RACK1 for activation of MCM7 and cell growth.

MCM7 is one of the pivotal DNA replication licensing factors in controlling DNA synthesis and cell entry into S phase. Its expression and DNA copy number are some of the most predictive factors for the growth and behavior of human malignancies. In this study, we identified that MCM7 interacts with the receptor for activated protein kinase C 1 (RACK1), a protein kinase C (PKC) adaptor, in vivo and in vitro. The RACK1 binding motif in MCM7 is located at the amino acid 221-248. Knocking down RACK1 significantly reduced MCM7 chromatin association, DNA synthesis, and cell cycle entry into S phase. Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate dramatically decreased MCM7 DNA replication licensing and induced cell growth arrest. Activation of PKC induced redistribution of RACK1 from nucleus to cytoplasm and decreased RACK1-chromatin association. The MCM7 mutant that does not bind RACK1 has no DNA replication licensing or oncogenic transformation activity. As a result, this study demonstrates a novel signaling mechanism that critically controls DNA synthesis and cell cycle progression.