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Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype. [ABSTRACT FROM AUTHOR]

Pre-laboratory briefing on concepts and procedures usually takes up a lot of lesson time as part of an already tight course schedule, leaving students with insufficient time to conduct experiments, connect the experiments to theories, and acquire subject-specific experimental skills. The flipped classroom approach seems to be a potential solution to enable students to conduct pre-laboratory learning prior to class, endeavoring to help students maximize the benefits of the experiment learning experience in science. In this study, a "Flipped-Experiment-Consolidate" (FEC) model was proposed for laboratory learning and teaching, and it was implemented in an undergraduate physics course during two academic years. A two-cycle action research study was conducted to evaluate the effectiveness of the proposed FEC model, and this involved two cohorts of students from different academic years, nineteen participants from academic year 2018 and seventeen participants from academic year 2019. A mixed-method design was used with the Flipped Learning Environment Questionnaire (FLEQ), semi-structured interviews, and the rubric for teachers' reflection on their flipped teaching. Findings from both action cycles indicated the need to integrate a flexible assessment (e.g., follow-up quiz, worksheet) into pre-laboratory learning to help foster students to take ownership of their learning. Without proper assessment paired up with the pre-laboratory learning activities, students may be unable to self-check and monitor their learning consistently and clearly. Additionally, there was a significant difference in students' incentive in the second action cycle, where course grades were bundled with the completion of pre-laboratory learning. [ABSTRACT FROM AUTHOR]

Objectives To assess the effect of sildenafil on monocrotaline-induced right ventricular (RV) remodeling and investigate the possible mechanism. Methods Rats were subcutaneously injected with monocrotaline to establish an RV remodeling model and then administered sildenafil (25 mg/kg) from days 1 to 28. After 28 days of administration, the RV systolic pressure and the RV hypertrophy index (RVHI) were measured. The morphology of the right ventricle was observed by H&E staining. The ultrastructure of the right ventricle was observed using a transmission electron microscope. The myocardial apoptosis of the right ventricle was evaluated by TUNEL staining. The protein expression of apoptosis-related proteins and PPARs were examined by western blotting. Key findings The results indicated that sildenafil decreased the RV systolic pressure and RVHI, and improved the microstructure and ultrastructure of the right ventricle in monocrotaline-induced rats. In addition, sildenafil suppressed myocardial apoptosis and promoted the protein expression of PPARs of the right ventricle in monocrotaline-induced rats. Conclusion Sildenafil inhibits RV remodeling in monocrotaline-induced rats, which might be partially mediated by reducing myocardial apoptosis and activating PPARs. [ABSTRACT FROM AUTHOR]