Left bundle branch area pacing improving the left atrial outcomes in pace-dependent patients compared with right ventricular outflow tract septal pacing.

BACKGROUND: Recent studies suggested that the left bundle branch area pacing (LBBAP) has a better efficacy to reduce QRS duration and produce a lower pacing threshold than the conventional right ventricular outflow tract septal pacing (RVOP), which resulted in a better cardiac function and ventricular synchronization. However, whether the LBBAP has a better efficacy in improving left atrial structure, function in pace-dependent patients compared with RVOP has not been well studied. OBJECTIVE: The purpose of this study was to compare the atrial outcomes of pace-dependent patients who received LBBAP or RVOP procedures. METHODS AND RESULTS: A total of 72 patients (including II° AVB, high AVB, and III° AVB, excluding atrial fibrillation patients with atrioventricular block) consecutively enrolled in this single-center prospective clinical study and randomly assigned to the RVOP group and the LBBP group with 36 patients. All patients were pace-dependent. The changes in echocardiogram, speckle-tracking echocardiography, brain natriuretic peptide (BNP), and 6-min walking distance were documented and compared between two groups at baseline, 7 days, 1, 3, and 6 months after the implantation. There were no significant differences in baseline characteristics between the two groups. The results of the study were as following: (1) left atrial structure index: Our study indicated that there are no significant differences in left atrial anteroposterior dimension (LAAPD), left atrial superoinferior dimension, and left atrial mediolateral dimension between two groups. While the LAAPD in the LBBAP group was significantly reduced at 6 months after implantation ([38.22 ± 2.17] mm vs. [34.13 ± 1.59] mm, p < .05). (2) Left atrial strain index: We observed that the S% was significantly improved in both groups at 3 and 6 months after implantation but more prominent in the LBBAP group at 6 months (36.94 ± 11.67 vs. 25.87 ± 8.93, p = .01). SRs, SRe were improved in the RVOP group at 6 months after implantation but was further significantly increased in the LBBAP group. Similarly, the SRa in the LBBAP group was significantly better than the RVOP group after 6 months (-2.11 ± 0.75 vs. -2.51 ± 0.70, p = .04). (3) Left atrial ejection index: LAEF% in the LBBAP group was significantly improved compared with the RVOP group (60.02 ± 1.88 vs. 53.65 ± 2.45, p = .047) and baseline (60.02 ± 1.88 vs. 49.68 ± 2.75, p < .05) at 6 months after the surgery. (4) Left ventricular ejection index: The LVEF% in the LBBAP group was significantly increased than the RVOP group after 6 months (69.14 ± 4.99 vs. 64.60 ± 4.84, p = .01) and the BNP level was significantly lower in the LBBAP group compared with the RVOP group at 7 days, 1, 3, and 6 months after implantation (p < .05). (5) 6-min walking distance: the 6-min walking distance was significantly increased at 3 and 6 months after implantation compared with that before (p < .05) in both groups, but was more prominent in LBBAP groups ([483.03 ± 11.02] m vs. [431.09 ± 10.69] m,p < .05). CONCLUSION: Compared with the traditional RVOP, the LBBAP procedure increased left atrial myocardial stress as well as left atrial ejection in pace-dependent patients at follow-up to 6 months.

The risk of ischemic stroke significantly increases in individuals with blepharitis: A population-based study involving 424,161 patients.

INTRODUCTION: To investigate the association of blepharitis and ischemic stroke. METHODS: This nationwide retrospective cohort study used population-based data in Taiwan. Individuals aged 20 and above with diagnosis of blepharitis was included based on electrical medical records. After exclusion of ineligible cases, 424,161 patients were identified between 2008 and 2018. The blepharitis and non-blepharitis cohorts were matched based on sex, age, and comorbidities. Multivariable-adjusted Cox proportional hazards model was adopted to calculate the hazard ratio and 95% confidence interval (CI) between blepharitis and non-blepharitis cohorts. The incidence of ischemic stroke was estimated by Kaplan-Meier analysis. RESULTS: 424,161 pairs of blepharitis cohort and non-blepharitis cohort were 1:1 propensity score matched for statistical analysis. Patients with blepharitis had significantly increased risk of ischemic stroke compared with the individuals without blepharitis (adjusted hazard ratio 1.32, 95% CI 1.29-1.34, P < 0.001). A significantly higher risk of ischemic stroke was observed in blepharitis cohort with a previous diagnosis of cancer than in those without cancer (P for interaction < 0.0001). Kaplan-Meier survival analysis revealed the cumulative incidence of ischemic stroke increased in the blepharitis cohort compared with that in the non-blepharitis cohort in 10 years (log-rank P < 0.001). The follow-up period analysis further indicated 1.41-fold adjusted hazard (95% CI 1.35-1.46, P < 0.001) of ischemic stroke within a year after blepharitis diagnosis. CONCLUSIONS: Patients with blepharitis had an elevated risk of developing ischemic stroke. Early treatment and active surveillance are suggested for patients with chronic blepharitis. Further research is required to determine the casual relationship between blepharitis and ischemic stroke, as well as the underlying mechanism.

Crocetin protects cardiomyocytes against hypoxia/reoxygenation injury by attenuating Drp1-mediated mitochondrial fission via PGC-1α.

BACKGROUND: Saffron (Crocus sativus L.) has been traditionally used as food, spice, and medicine. Crocetin (CRT), as main bioactive component of saffron, has accumulated pieces of beneficial evidence on myocardial ischemia/reperfusion (I/R) injury. However, the mechanisms are poorly explored. This study aims to investigate the effects of CRT on H9c2 cells under hypoxia/reoxygenation (H/R) and elucidated the possible underlying mechanism. METHODS: H/R attack was performed on H9c2 cells. Cell counting kit-8 was used to detect the cell viability. Cell samples and culture supernatants were evaluated via commercial kits to measure the superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and cellular adenosine triphosphate (ATP) content. Various fluorescent probes were used to detect cell apoptosis, intracellular and mitochondrial reactive oxygen species (ROS) content, mitochondrial morphology, mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (mPTP) opening. Proteins were evaluated via Western Blot. RESULTS: H/R exposure severely reduced cell viability and increased LDH leakage. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) suppression and dynamin-related protein 1 (Drp1) activation were coincided with excessive mitochondrial fission, mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse in H9c2 cells treated with H/R. Mitochondria fragmentation under H/R injury induced ROS over-production, oxidative stress, and cell apoptosis. Notably, CRT treatment significantly prevented mitochondrial fission, mPTP opening, MMP loss, and cell apoptosis. Moreover, CRT sufficiently activated PGC-1α and inactivated Drp1. Interestingly, mitochondrial fission inhibition with mdivi-1 similarly suppressed mitochondrial dysfunction, oxidative stress and cell apoptosis. However, silencing PGC-1α with small interfering RNA (siRNA) abolished the beneficial effects of CRT on H9c2 cells under H/R injury, accompanied with increased Drp1 and p-Drp1ser616 levels. Furthermore, over-expression of PGC-1α with adenovirus transfection replicated the beneficial effects of CRT on H9c2 cells. CONCLUSIONS: Our study identified PGC-1α as a master regulator in H/R-injured H9c2 cells via Drp1-mediated mitochondrial fission. We also presented the evidence that PGC-1α might be a novel target against cardiomyocyte H/R injury. Our data revealed the role of CRT in regulating PGC-1α/Drp1/mitochondrial fission process in H9c2 cells under the burden of H/R attack, and we suggested that modulation of PGC-1α level may provide a therapeutic target for treating cardiac I/R injury.

Multiple micromeningiomas coexist with primary lung adenocarcinoma: A case report.

Cases of multiple ectopic meningiomas in the lung coexisting with pulmonary malignancies are extremely rare in the clinic. On imaging, it is difficult to distinguish multiple ectopic meningiomas from lung cancer, which puts forward higher requirements for treatment. A 65-year-old female patient was admitted to our department for multiple nodules in both lungs. The patient underwent thoracoscopic wedge resection and segmental resection. Postoperative pathological examination found lung meningioma, atypical adenomatoid hyperplasia (AAH), carcinoma in situ (AIS), invasive adenocarcinoma, and other pathological types. In this case, pulmonary meningioma, AAH, AIS, and invasive adenocarcinoma of various pulmonary nodules were observed. This case, which has not been reported before, is unique in that it has multiple pathologic types in one organ. This puts forward higher requirements for clinical diagnosis and treatment.

Discovery of highly potent and selective 7-ethyl-10-hydroxycamptothecin-glucose conjugates as potential anti-colorectal cancer agents.

7-Ethyl-10-hydroxycamptothecin (SN38), a highly potent metabolite of irinotecan, has an anticancer efficacy 100-1000 folds more than irinotecan in vitro. However, the clinical application of SN38 has been limited due to the very narrow therapeutic window and poor water solubility. Herein, we report the SN38-glucose conjugates (Glu-SN38) that can target cancer cells due to their selective uptake via glucose transporters, which are overexpressed in most cancers. The in vitro antiproliferative activities against human cancer cell lines and normal cells of Glu-SN38 were investigated. One of the conjugates named 5b showed high potency and selectivity against human colorectal cancer cell line HCT116. Furthermore, 5b remarkably inhibited the growth of HCT116 in vivo. These results suggested that 5b could be a promising drug candidate for treating colorectal cancer.

The effect of different preoperative left atrial appendage emptying speeds on left atrial function in patients with persistent atrial fibrillation after left atrial appendage closure combined with catheter ablation.

OBJECTIVE: The present study aimed to investigate whether different preoperative left atrial appendage emptying speeds (LAAEVs) have an effect on left atrial function in patients with sinus arrhythmia after left atrial appendage closure (LAAC) combined with catheter ablation (CA). METHODS: A total of 163 patients with persistent non-valvular atrial fibrillation who received combined LAAC+CA surgery were included in the present study. Regular follow-up was conducted for 12 months, and patients with complete data and successful sinus rhythm recovery were selected as the study subjects (n = 82). The patients were divided into two groups: the LAAEV < 25 cm/s group and the LAAEV ≥ 25 cm/s group (n = 41 each). The propensity score was used for matching according to gender, age, CHA2DS2-VASc score, and HAS-BLED score. The changes in the two groups in LA structure, storage function, conduit function, and pump function were compared. RESULTS: Before surgery, the maximum LA volume (LAVmax) and minimum LA volume (LAVmin) were greater in the LAAEV < 25 cm/s group than in the LAAEV ≥ 25 cm/s group. The LA storage function (eg. Ƹ and SRs), conduit function (eg. SRe), and pump function (eg. SRa) were all worse in the LAAEV < 25 cm/s group than in the LAAEV ≥ 25 cm/s group. After the combined LAAC+CA surgery, the LA storage, conduit, and pump functions improved in both groups. At 12 months after surgery, there were no statistically significant differences between the two groups. CONCLUSION: Before combined LAAC+CA surgery, the LA structure and function of the LAAEV < 25 cm/s group were worse than those of the LAAEV ≥ 25 cm/s group. However, after LAAC+CA surgery, the LA structure and function of the patients were improved, and there were no significant differences between the two groups. Inferred improvement in LA structure and function in the LAAEV < 25 cm/s group was superior to that in the LAAEV ≥ 25 cm/s group.

[Effect of electroacupuncture on endometrial receptivity and IVF-ET pregnancy outcomes in patients with diminished ovarian reserve].

OBJECTIVE: To explore the effect of electroacupuncture on endometrial receptivity and the pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET) in the patients with diminished ovarian reserve (DOR). METHODS: Sixty-eight patients of DOR undertaken IVF-ET were randomized into an observation group (34 cases, 2 cases dropped off) and a control group (34 cases, 1 case dropped off). In the control group, endometrial preparation was performed according to the routine protocol. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Geshu (BL 17), Shenshu (BL 23), Mingmen (GV 4), Shiqizhui (EX-B 8), Ciliao (BL 32), Zhongliao (BL 33), Tianshu (ST 25), Qihai (CV 6) and Guanyuan (CV 4), etc. Electric stimulation was given at Ciliao (BL 32)-Zhongliao(BL 33), Tianshu (ST 25)-Zigong (EX-CA 1), with disperse-dense wave, 2 Hz/15 Hz in frequency and tolerable current in intensity. Electroacupuncture was given once every two days, 3 times weekly, lasing 3 menstrual cycles till 1 day before embryo transfer. The endometrial thickness and morphology were observed on the day of human chorionic gonadotropin (HCG) of egg retrieval cycle, the day of endometrial transformation in frozen-thawed embryo transfer (FET) cycle and the day of embryo transfer in both groups successively; as well as HCG positive rate, clinical pregnancy rate, embryo implantation rate and live birth rate. RESULTS: In the observation group, the proportion of type A endometrium on the embryo transfer day was higher than those on HCG day of the egg retrieval cycle and the endometrial transformation day of FET cycle (P<0.05), and also higher than that of the control group (P<0.01). In the observation group, HCG positive rate, clinical pregnancy rate, embryo implantation rate and live birth rate were 75.0% (24/32), 71.9% (23/32), 47.4% (27/57) and 56.3% (18/32) respectively, and all higher than 36.4% (12/33), 30.3% (10/33), 18.0% (11/61) and 15.2% (5/33) in the control group separately (P<0.01). CONCLUSION: Electroacupuncture improves the endometrial receptivity and IVF-ET pregnancy outcomes in the patients of diminished ovarian reserve.

Multidomain Narrowband Interference Intelligent Suppression Method Based on Cognitive Radio and MIMO in UAV Data Link.

In this paper, a kind of antinarrowband interference intelligent method based on cognitive MIMO (multiple-input multiple-output) airspace, time domain, frequency domain, and code domain is proposed. This method combines perceptual technology, spread spectrum code, MIMO space-time coding, and so on. Through coordinating space, time, frequency, and code element diversity, the narrowband interference in the UAV (unmanned aerial vehicle) monitoring and control link is effectively countered. The input and output model of MIMO monitoring and control link of UAV with natural interference are described. Then, the realization principle of the multidomain antinarrowband interference method based on CR-MIMO is presented, and the corresponding models of receiving and transmitting are also given. Finally, the anti-interference performance of the proposed method is analyzed theoretically and validated through simulation experiments, and the effectiveness of the proposed method is verified.

Two-Phase Extraction Processes, Physicochemical Characteristics, and Autoxidation Inhibition of the Essential Oil Nanoemulsion of Citrus reticulata Blanco (Tangerine) Leaves.

Combined ultrasound-microwave techniques and pre-enzymatic treatment (hemicellulase and cellulase) enhance essential oil isolation from Citrus reticulata Blanco (tangerine) leaves (CrBL). Subsequently, synergistic effects of modified amorphous octenyl succinic anhydride starch (OSA-MS), almond oil, and high-energy microfluidics were studied in synergy with ultrasound techniques in the production of CrBL essential oil (CrBL-EO) nanoemulsion (CrBL-EONE). GC-MS was used to study the extraction technique. Dynamic light scattering (DLS) analysis was used with confocal laser scanning microscopy (CLSM) techniques to investigate the nanoemulsion matrices' physical and chemical properties. The D-limonene nanoemulsion (D-LNE) reached the optimal size of droplets (65.3 ± 1.1 r.nm), polydispersity index (PDI) (0.167 ± 0.015), and ζ-potential (-41.0 ± 0.4 mV). Besides, the CrBL-EONE obtained the optimal size of droplets (86.5 ± 0.5 r.nm), PDI (0.182 ± 0.012), and ζ-potential (-40.4 ± 0.8 mV). All the nanoparticle treatments showed significant values in terms of the creaming index (CI%) and inhibition activity (IA%) in the ß-carotene/linoleate system with a low degradation rate (DR). The current study's findings showed that integrated ultrasound-microwave techniques and pre-enzymatic treatment could enhance the extraction efficiency of the CrBL-EO. In addition, OSA-MS and almond oil can also be employed to produce CrBL-EONE and D-LNE.

Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis.

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.

A comprehensive prognostic analysis of osimertinib treatment in advanced non-small cell lung cancer patients with acquired EGFR-T790M mutation: a real-world study.

PURPOSE: Osimertinib is the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with T790M mutation after the failure of first-/second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). We comprehensively analyzed factors that affect the therapeutic efficacy of the osimertinib treatment in NSCLC patients. METHODS: 351 NSCLC patients with T790M mutation receiving osimertinib treatment were included. We investigated the value of different factors in predicting the clinical outcomes of the osimertinib therapy, including progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Logistic and COX regression were used to identify prognosticators. RESULTS: In osimertinib therapy, EGFR mutation status (19Del/L858R) at initial diagnosis and the therapeutic choice of prior EGFR-TKI agent was not associated with patients' prognosis. Notably, the PFS of the prior EGFR-TKI was independently related to ORR (OR, 95% CI 0.98, 0.96-1.00, p = 0.030), PFS (HR, 95% CI 0.98, 0.97-1.00, p = 0.009) and OS (HR, 95% CI 0.96, 0.93-0.98, p < 0.001) of osimertinib treatment. Among distinct organ metastases, only bone metastasis was related to the efficacy of osimertinib, in terms of ORR (OR, 95% CI 1.97, 1.27-3.06, p = 0.002), PFS (HR, 95% CI 1.55, 1.18-2.03, p = 0.001) and OS (HR, 95% CI 1.81, 1.27-2.59, p = 0.001). However, the therapeutic efficacy of osimertinib was not further impacted by the accumulation of metastatic organs. A performance status score of 2-4 was also an adverse prognosticator for the osimertinib therapy. CONCLUSION: PFS of the prior EGFR-TKI treatment, performance status score and bone metastasis were independent prognosticators of the osimertinib treatment. These findings may facilitate clinicians in the decision-making of osimertinib.

Machine Learning-Based CT Radiomics Analysis for Prognostic Prediction in Metastatic Non-Small Cell Lung Cancer Patients With EGFR-T790M Mutation Receiving Third-Generation EGFR-TKI Osimertinib Treatment.

BACKGROUND AND PURPOSE: As a third-generation EGFR tyrosine kinase inhibitor (TKI), osimertinib is approved for treating advanced non-small cell lung cancer (NSCLC) patients with EGFR-T790M mutation after progression on first- or second-generation EGFR-TKIs such as gefitinib, erlotinib and afatinib. We aim at exploring the feasibility and effectiveness of using radiomic features from chest CT scan to predict the prognosis of metastatic non-small cell lung cancer (NSCLC) patients with EGFR-T790M mutation receiving second-line osimertinib therapy. METHODS: Contrast-enhanced and unenhanced chest CT images before osimertinib treatment were collected from 201 and 273 metastatic NSCLC patients with EGFR-T790M mutation, respectively. Radiomic features were extracted from the volume of interest. LASSO regression was used to preliminarily evaluate the prognostic values of different radiomic features. We then performed machine learning-based analyses including random forest (RF), support vector machine (SVM), stepwise regression (SR) and LASSO regression with 5-fold cross-validation (CV) to establish the optimal radiomic model for predicting the progression-free survival (PFS) of osimertinib treatment. Finally, a combined clinical-radiomic model was developed and validated using the concordance index (C-index), decision-curve analysis (DCA) and calibration curve analysis. RESULTS: Disease progression occurred in 174/273 (63.7%) cases. CT morphological features had no ability in predicting patients' prognosis in osimertinib treatment. Univariate COX regression followed by LASSO regression analyses identified 23 and 6 radiomic features from the contrast-enhanced and unenhanced CT with prognostic value, respectively. The 23 contrast-enhanced radiomic features were further used to construct radiomic models using different machine learning strategies. Radiomic model built by SR exhibited superior predictive accuracy than RF, SVR or LASSO model (mean C-index of the 5-fold CV: 0.660 vs. 0.560 vs. 0.598 vs. 0.590). Adding the SR radiomic model to the clinical model could remarkably strengthen the C-index of the latter from 0.672 to 0.755. DCA and calibration curve analyses also demonstrated good performance of the combined clinical-radiomic model. CONCLUSIONS: Radiomic features extracted from the contrast-enhanced chest CT could be used to evaluate metastatic NSCLC patients' prognosis in osimertinib treatment. Prognostic models combing both radiomic features and clinical factors had a great performance in predicting patients' outcomes.

Radiomic assessment as a method for predicting tumor mutation burden (TMB) of bladder cancer patients: a feasibility study.

BACKGROUND: Tumor mutation burden (TMB) is an emerging prognostic biomarker of immunotherapy for bladder cancer (BLCA). We aim at investigating radiomic features' value in predicting the TMB status of BLCA patients. METHODS: Totally, 75 patients with BLCA were enrolled. Radiomic features extracted from the volume of interest of preoperative pelvic contrast-enhanced computed tomography (CECT) were obtained for each case. Unsupervised hierarchical clustering analysis was performed based on radiomic features. Sequential univariate Logistic regression, the least absolute shrinkage and selection operator (LASSO) regression and the backward stepwise regression were used to develop a TMB-predicting model using radiomic features. RESULTS: The unsupervised clustering analysis divided the total cohort into two groups, i.e., group A (32.0%) and B (68.0%). Patients in group A had a significantly larger proportion of having high TMB against those in group B (66.7% vs. 41.2%, p = 0.039), indicating the intrinsic ability of radiomic features in TMB-predicting. In univariate analysis, 27 radiomic features could predict TMB. Based on six radiomic features selected by logistic and LASSO regression, a TMB-predicting model was built and visualized by nomogram. The area under the ROC curve of the model reached 0.853. Besides, the calibration curve and the decision curve also revealed the good performance of the model. CONCLUSIONS: Our work firstly proved the feasibility of using radiomics to predict TMB for patients with BLCA. The predictive model based on radiomic features from pelvic CECT has a promising ability to predict TMB. Future study with a larger cohort is needed to verify our findings.

The Prognostic Value of Radiomics Features Extracted From Computed Tomography in Patients With Localized Clear Cell Renal Cell Carcinoma After Nephrectomy.

BACKGROUND AND PURPOSE: Radiomics is an emerging field of quantitative imaging. The prognostic value of radiomics analysis in patients with localized clear cell renal cell carcinoma (ccRCC) after nephrectomy remains unknown. METHODS: Computed tomography images of 167 eligible cases were obtained from the Cancer Imaging Archive database. Radiomics features were extracted from the region of interest contoured manually for each patient. Hierarchical clustering was performed to divide patients into distinct groups. Prognostic assessments were performed by Kaplan-Meier curves, COX regression, and least absolute shrinkage and selection operator COX regression. Besides, transcriptome mRNA data were also included in the prognostic analyses. Endpoints were overall survival (OS) and disease-free survival (DFS). Concordance index (C-index), decision curve analysis and calibration curves with 1,000 bootstrapping replications were used for model's validation. RESULTS: Hierarchical clustering groups from nephrographic features and mRNA can divide patients into different prognostic groups while clustering groups from corticomedullary or unenhanced phase couldn't distinguish patients' prognosis. In multivariate analyses, 11 OS-predicting and eight DFS-predicting features were identified in nephrographic phase. Similarly, seven OS-predictors and seven DFS-predictors were confirmed in mRNA data. In contrast, limited prognostic features were found in corticomedullary (two OS-predictor and two DFS-predictors) and unenhanced phase (one OS-predictors and two DFS-predictors). Prognostic models combining both nephrographic features and mRNA showed improved C-index than any model alone (C-index: 0.927 and 0.879 for OS- and DFS-predicting, respectively). In addition, decision curves and calibration curves also revealed the great performance of the novel models. CONCLUSION: We firstly investigated the prognostic significance of preoperative radiomics signatures in ccRCC patients. Radiomics features obtained from nephrographic phase had stronger predictive ability than features from corticomedullary or unenhanced phase. Multi-omics models combining radiomics and transcriptome data could further increase the predictive accuracy.

Proangiogenic Peptide Nanofiber Hydrogels for Wound Healing.

Rapid vascularization is vital for dermal regeneration, nutrient and nutrition transfer, metabolic waste removal, and prevention of infection. This study reports on a series of proangiogenic peptides designed to undergo self-assembly and promote angiogenesis and hence skin regeneration. The proangiogenic peptides comprised an angiogenic peptide segment, GEETEVTVEGLEPG, and a ß-sheet structural peptide sequence. These peptides dissolved easily in ultrapure water and rapidly self-assembled into hydrogels in a pH-dependent manner, creating three-dimensional fibril network structures and nanofibers as revealed by a scanning microscope and a transmission electron microscope. In vitro experiments showed that the peptide hydrogels favored adhesion and proliferation of mouse fibroblasts (L929) and human umbilical vein endothelial cells (HUVECs). In particular, many connected tubes were formed in the HUVECs after 8 h of culture on the peptide hydrogels. In vivo experiments demonstrated that new blood vessels grew into the proangiogenic peptide hydrogels within 2 weeks after subcutaneous implantation in mice. Moreover, the proangiogenic-combined hydrogels exhibited faster repair cycles and better healing of skin defects. Collectively, the results indicate that the proangiogenic peptide hydrogels are a promising therapeutic option for skin regeneration.

MiR-590-5p regulates cell proliferation, apoptosis, migration and invasion in oral squamous cell carcinoma by targeting RECK.

OBJECTIVE: To discover the role of miR-590-5p in oral squamous cell carcinoma (OSCC) progression and the corresponding mechanism via the targeting RECK. METHODS: OSCC (n=85) and normal oral tissues (n=60) were collected to quantify the miR-590-5p expression by using qRT-PCR. Then SCC-15 and OEC-M1 cells were selected and divided into Mock, inhibitor NC, miR-590-5p inhibitor, si-RECK and miR-590-5p inhibitor + si-RECK groups. Dual-luciferase reporter gene assay was used to verify if miR-590-5p could target RECK. The biological behaviors of OSCC cells were evaluated by MTT, Wound-healing, Transwell and Flow cytometry. The expression of miR-590-5p and RECK was measured by qRT-PCR and Western blotting , respectively. RESULTS: Overexpression of miR-590-5p was found in OSCC tissues. The expression of miR-590-5p was significantly associated with the clinical TNM stage, differentiation degree, and lymph node metastasis of OSCC. RECK was identified as a direct target of miR-590-5p. Compared with the Mock group, cells in the miR-590-5p inhibitor group were decreased in terms of proliferation, invasion, and migration, and increased in cell apoptosis, accompanied by down-regulated miR-590-5p, Bcl-2/Bax and MMP-9, and up-regulated RECK. By contrast, si-RECK group presented completely opposite changes, and si-RECK reversed the inhibitory effect of miR-590-5p inhibitor on the OSCC cell growth. CONCLUSION: MiR-590-5p expression was obviously increased in OSCC, and inhibiting miR-590-5p enhanced the expression of its target gene RECK, thereby suppressing proliferation, migration and invasion of OSCC cells and promoting apoptosis of OSCC cells.

A novel prognostic model predicting the long-term cancer-specific survival for patients with hypopharyngeal squamous cell carcinoma.

BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) is a rare type of head and neck cancer with poor prognosis. However, till now, there is still no model predicting the survival outcomes for HSCC patients. We aim to develop a novel nomogram predicting the long-term cancer-specific survival (CSS) for patients with HSCC and establish a prognostic classification system. METHODS: Data of 2021 eligible HSCC patients were retrieved from the Surveillance, Epidemiology and End Results database between 2010 and 2015. We randomly split the whole cases (ratio: 7:3) into the training and the validation cohort. Cox regression as well as the Least absolute shrinkage and selection operator (LASSO) COX were used to select significant predictors of CSS. Based on the beta-value of these predictors, a novel nomogram was built. The concordance index (C-index), the calibration curve and the decision curve analysis (DCA) were utilized for the model validation and evaluation using the validation cohort. RESULTS: In total, cancer-specific death occurred in 974/2021 (48.2%) patients. LASSO COX indicated that age, race, T stage, N stage, M stage, surgery, radiotherapy and chemotherapy are significant prognosticators of CSS. A prognostic model based on these factors was constructed and visually presented as nomogram. The C-index of the model was 0.764, indicating great predictive accuracy. Additionally, DCA and calibration curves also demonstrated that the nomogram had good clinical effect and satisfactory consistency between the predictive CSS and actual observation. Furthermore, we developed a prognostic classification system that divides HSCC patients into three groups with different prognosis. The median CSS for HSCC patients in the favorable, intermediate and poor prognosis group was not reached, 39.0-Mo and 10.0-Mo, respectively (p < 0.001). CONCLUSIONS: In this study, we constructed the first nomogram as well as a relevant prognostic classification system that predicts CSS for HSCC patients. We believe these tools would be helpful for clinical practice in patients' consultation and risk group stratification.

Inflammatory Response after Different Ablation Strategies for Paroxysmal Atrial Fibrillation.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) has been gaining popularity; however, the trend of inflammatory response markers in patients treated with different catheter ablation strategies over time and their predictability of AF recurrence remain unknown. METHODS: A total of 210 patients with AF were enrolled and grouped according to surgical mode as follows: freeze group, RF group, and freeze3D group. The subjects were tested for related indexes before and after surgery. To determine AF recurrence during follow up, 24-h ambulatory electrocardiography was performed at two, three, six, and 12 months after surgery. RESULTS: The inflammation indexes of the three groups peaked between one and three days after surgery but fell at different time points (P < .05). The recurrence rate of paroxysmal atrial fibrillation (PAF) was positively correlated with the increase in the percentage of white blood cells and neutrophils after surgery (P < .05). CONCLUSIONS: The postoperative inflammation indices peaked and fell at different time points after different catheter ablation methods. In addition, the recurrence rate of AF in patients treated with freeze3D is lower.

LncRNA DANCR regulates the growth and metastasis of oral squamous cell carcinoma cells via altering miR-216a-5p expression.

The study aims to investigate how DANCR can alter the growth and metastasis of oral squamous cell carcinoma (OSCC) cells by regulating miR-216a-5p. The expression of DANCR and miR-216a-5p in OSCC patients and cells were measured. SCC15 and CAL-27 cells were selected to divide into Control, sh-NC, DANCR shRNA, DANCR, miR-216a-5p mimic, and DANCR + miR-216a-5p mimic groups. Dual-luciferase reporter gene assay was performed for the verification of the targeting relationship between miR-216a-5p and DANCR/Bcl-2/KLF12. We also quantified the abilities of OSCC cells regarding proliferation, invasion, migration and apoptosis, and the expression levels of apoptosis-related proteins were measured. Finally, the tumor-bearing nude mice were established to verify the effect of DANCR in vivo. Up-regulated DANCR expression and down-regulated miR-216a-5p expression were observed in both OSCC tissues and cells, and they were proven strongly correlated to the histological grade, clinical staging and lymph node metastasis of OSCC patients. Dual-luciferase reporter gene assay showed a target relationship between DANCR and miR-216a-5p, as well as between miR-216a-5p and Bcl-2/KLF12. Both DANCR shRNA and miR-216a-5p mimic decreased proliferative, migration and invasive abilities of OSCC cells with increased cell apoptosis. However, DANCR group showed completely opposite trends. Moreover, miR-216a-5p mimic could reverse the role of DANCR in promoting tumor growth. In-vivo experiment confirmed the inhibitory role of DANCR shRNA in tumor growth and metastasis. We concluded that DANCR may promote the growth and metastasis of OSCC cells and suppress OSCC cell apoptosis by sponging miR-216a-5p.

Enhancement of the antitumor effect of HER2-directed CAR-T cells through blocking epithelial-mesenchymal transition in tumor cells.

The efficacy of chimeric antigen receptor T (CAR-T) cell therapy in solid tumors is far from satisfactory. In this study, we investigated the influence of epithelial-mesenchymal transition (EMT) on the antitumor effect of CAR-T cells and explored the potential efficacy of combining CAR-T cells with inhibitors targeting EMT. We successfully induced EMT in tumor cells with TGF-ß1, and the antitumor effect of HER2-directed CAR-T cells was significantly suppressed by EMT. Upregulation of PD-L1 was observed in tumor cells undergoing EMT, and change in PD-L1 expression during the EMT process was dependent on the MEK/ERK and PI3K/Akt pathways. Inhibition of the TGF-ß1 pathway could block the EMT process in tumor cells and restore their susceptibility to HER2-directed CAR-T cells in vitro. In addition, targeting the TGF-ß1 pathway significantly enhanced the antitumor effect of HER2-directed CAR-T cells in vivo. Our findings suggest that blocking EMT could potently enhance the antitumor effect of CAR-T cells, which provides a promising approach to improving the therapeutic efficacy of CAR-T cell therapy in solid tumors.