Bishonokiol A Induces Multiple Cell Death in Human Breast Cancer MCF-7 Cells

Objective: A dimeric neolignan, bishonokiol A (BHNKA) isolated from Magnolia grandiflora, significantly inhibits the proliferation of human breast cancer cells. However, the exact mechanism of BHNKA induced breast cancer cell death is unknown. In this study, we investigated the pharmacological mechanism underlying BHNKA induced MCF-7 cell death. Methods: Cell viability measurement was performed by the MTT assay. Flow cytometry with PI staining, DAPI staining, and electron microscopy were used to analyze cellular death modes. In addition, western blotting, siRNA transfection, ATP assay, and fluorescence microscopy were used to determine the mechanism of BHNKA induced MCF-7 cell death. Results: BHNKA induced cell death by apoptosis, necroptosis and autophagy at the same concentration and time in MCF-7 cells, and electron microscopy confirmed these results. The mechanism of BHNKA triggered apoptosis and autophagy in MCF-7 cells was primarily due to an increase in the Bax/Bcl-2 ratio and simultaneous up-regulation of LC3-II protein expression, respectively. BHNKA induced necroptosis by activation of the RIP1-RIP3-MLKL necroptosis cascade, up-regulation of cyclophilin D (CypD) protein expression to stimulate ROS generation. We further demonstrated that siRNA-mediated down-regulation of CypD protected against BHNKA induced cell death. Conclusions: These results suggest that BHNKA may be a potential lead compound for development as an anti-breast cancer agent for induction of multiple cell death pathways.     

养阴益气活血汤对慢性心力衰竭患者心功能及生活质量的影响

目的:研究养阴益气活血汤对慢性心力衰竭患者心功能和生活质量的影响。方法:将慢性心力衰竭患者86例随机分为2组。对照组采用常规西药治疗,观察组联合养阴益气活血汤治疗。观察比较2组左心室射血分数(LVEF)、左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、生活质量评分、中医证候积分、疗效和不良反应。结果:治疗后,2组LVEF升高,LVEDD、LVESD降低,且观察组LVEF高于对照组,LVEDD、LVESD低于对照组,差异有统计学意义(P<0.05)。治疗后,2组中医证候积分、生活质量评分均降低,且观察组中医证候积分、生活质量评分低于对照组,差异有统计学意义(P<0.05)。观察组总有效率为93.02%,对照组总有效率为76.74%,观察组总有效率高于对照组(P<0.05)。结论:养阴益气活血汤治疗慢性心力衰竭,能显著改善患者心功能,提高生活质量,安全可靠。     

Association Between Clinical Tumor Burden and Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non–Small-Cell Lung Cancer

BackgroundProgrammed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non–small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC.Patients and MethodsThe present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018. The clinical tumor burden was estimated using the baseline sum of the target lesions’ longest diameters (BSLDs), measured according to the Response Evaluation Criteria for Solid Tumors, and the baseline number of metastatic lesions (BNMLs).ResultsThe optimal cutoff values for predicting progression-free survival (PFS) were 5 for the BNMLs and 76 mm for the BSLDs, using the minimum P value method. The low-BNML group included 73 patients (44.8%). The median PFS was 12.2 months in the low-BNML group and 2.8 months in the high-BNML group (hazard ratio, 0.51; P = .0005). The low-BSLD group included 92 patients (56.4%). The median PFS was 9.6 months in the low-BSLD group and 3.4 months in the high-BSLD group (hazard ratio, 0.52; P = .0006). Multivariable analysis revealed that low-BSLD, low-BNML, nonsquamous histologic type and a PD-L1 tumor proportion score of ≥ 50% were independently associated with prolonged PFS.ConclusionsPD-L1 expression and the clinical tumor burden can predict the efficacy of PD-1/PD-L1 inhibitor monotherapy for NSCLC.     

Imaging Features of Pulmonary Immune-related Adverse Events

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.     

外科治疗56例心脏非黏液性肿瘤的临床分析

目的探讨心脏非黏液性肿瘤临床特点,总结外科治疗经验。方法对我院1996年10月至2005年3月进行外科治疗的56例心脏非黏液性肿瘤的临床资料进行回顾性分析,总结其临床表现、发生部位、肿瘤性质和外科治疗特点等。结果心脏非粘液性肿瘤占本院同期手术患者的0.14%,良性肿瘤28例,恶性肿瘤28例,其中继发性心脏肿瘤8例。良性肿瘤最常见的是生长在心室,共18例;恶性肿瘤最常见的生长部位是心房,共15例。外科治疗行急诊手术者12例。心包开窗引流术2例,探查术1例,术中肿瘤全部切除者26例,部分切除27例,术后住院期间死亡1例。结论心脏非黏液性肿瘤临床表现各异、病理类型多样、病变广泛,手术原则为尽可能切除肿瘤和保持心脏结构的完整性和功能。     

A case of acute heart failure associated with Guillain-Barré syndrome

Abstract Guillain-Barré syndrome (GBS) is a disease of the peripheral nervous system, which is caused by aberrant immune responses directed against some components of peripheral nerves. GBS is rarely accompanied by cardiovascular involvement. We describe a case of acute neuropathy complicated by sudden heart failure and left ventricular dysfunction which had a presumably neurogenic origin. Pathogenesis of acute heart failure is probably due to transitorial stunned myocardium and neurogenic cardiac injury. We show a rare case of transitorial and acute cardiac dysfunction by echocardiography and laboratory markers of heart failure.     

Primary Prevention of Sudden Cardiac Death: Can We Afford the Cost of Cardioverter-Defibrillators? Data from the Search-MI Registry-Italian Sub-study

Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies.
Methods and Results: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5–7 year time horizon, the average daily cost was estimated to be €4.60–€6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90–$11.40.
Conclusions: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources.