Objectives To examine selective macrophage differentiation occurring in areas of intraplaque hemorrhage in human atherosclerosis. Background Macrophage subsets are recognized in atherosclerosis but the stimulus for and importance of differentiation programs remains unknown. Methods We used freshly isolated human monocytes, a rabbit model, and human atherosclerotic plaques to analyze macrophage differentiation in response to hemorrhage. Results Macrophages characterized by high expression of both mannose and CD163 receptors preferentially exist in atherosclerotic lesions at sites of intraplaque hemorrhage. These hemoglobin (Hb)-stimulated macrophages, M(Hb), are devoid of neutral lipids typical of foam cells. In vivo modeling of hemorrhage in the rabbit model demonstrated that sponges exposed to red cells showed an increase in mannose receptor positive macrophages only when these cells contained hemoglobin (Hb). Cultured human monocytes exposed to hemoglobin:haptoglobin complexes (Hb:Hp), but not IL-4, expressed the M(Hb) phenotype and were characterized by their resistance to cholesterol loading and upregulation of ABC transporters. M(Hb) demonstrated increased ferroportin (FPN) expression, reduced intracellular iron, and reactive oxygen species (ROS). Degradation of FPN using hepcidin increased ROS, inhibited ABCA1 expression, and cholesterol efflux to ApoAI, suggesting reduced ROS triggers these effects. Knockdown of liver x receptor alpha (LXRα) inhibited ABC transporter expression in M(Hb) and macrophages differentiated in the anti-oxidant superoxide dismutase. Lastly, liver X receptor α (LXR) luciferase reporter activity was increased in M(Hb) and significantly reduced by overnight treatment with hepcidin. Collectively, these data suggest reduced ROS triggers LXRα activation and macrophage reverse cholesterol transport (RCT). Conclusions Hb is a stimulus for macrophage differentiation in human atherosclerotic plaques. A reduction of macrophage intracellular iron plays an important role in this non- foam cell phenotype by reducing ROS, which drives transcription of ABC transporters through activation of LXRα. Reduction of macrophage intracellular iron may be a promising avenue to increase macrophage RCT.

While American educators fret about the mediocre educational performance of American students in international contests (e.g. the Program for International Student Assessment) and wonder why the Chinese education system produces such high-achieving students, educators, journalists, and public officials in China want to know what causes and how to prevent the high levels of academic stress that Chinese students, their families, and their school systems experience. So far, much of the blame for these toxic levels of stress has been directed to the Gaokao, the Chinese national college entrance exam that takes place in June each year. But to date, top-down Chinese educational reforms have been ineffective in reducing the problem. In this article, we build a case for strengthening bottom-up efforts at the school level in China and propose an evidence-based approach for addressing the challenge of academic stress experienced by Chinese students.

Background On May 8, 2018, the China National Medical Products Administration (NMPA) approved anlotinib, an orally administered anti-angiogenesis inhibitor, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have progressed after treatment with two or more lines of prior systemic chemotherapy. Main body of the abstract China NMPA reviewed and inspected a regional double-blinded, placebo-controlled, Phase III trial comparing the overall survival (OS) of NSCLC patients between the anlotinib and placebo arms. A total of 437 patients were randomized (2:1) to receive either anlotinib ( n = 294) or placebo ( n = 143) once daily on a 2-week on and 1-week off schedule. Patients with epidermal growth factor receptor ( EGFR ) or activating anaplastic lymphoma kinase ( ALK ) genomic tumor aberrations should have disease progression on NMPA-approved therapy. Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China. The approval was based on a statistically and clinically significant improvement in median OS with anlotinib (9.46 months) compared with placebo [6.37 months; hazard ratio (HR]) = 0.70, 95% confidence interval (CI) = 0.55–0.89; two-sided log-rank P = 0.002]. The confirmed objective response rate (ORR) was 9.2% in the anlotinib arm and 0.7% in the placebo arm. The median duration of response (DoR) was 4.83 months, with a 95% CI of 3.31–6.97 months. The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors. Common adverse drug reactions (ADRs) in anlotinib-treated patients included hypertension (67.4%), hand–foot syndrome (43.9%), hemoptysis (14.0%), thyroid stimulating hormone (TSH) elevation (46.6%), and corrected QT interval (QTc) prolongation (26.2%). Short conclusion Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.

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Background Empathy is an important element of the physician-patient relationship and is a critical personality trait for medical students. However, research has shown that it declines during undergraduate medical education. It is still unclear how empathy interrelates with the psychological elements of medical students, in particular, self-esteem. This study examined the relationship between empathy and self-esteem to explore other possible methods to improve medical students’ empathy. Methods A stratified sampling strategy was used to select 1690 medical students from 3 medical institutions in Shanghai as study participants. The questionnaires used to collect data included the Jefferson Scale of Physician Empathy-Student Version (JSPE-S), the Rosenberg Self-esteem Scale (RSES), and a self-made inventory on personal information. Descriptive analysis, independent t -test, One-Way ANOVA, and linear regression were used to analyze the data. Results The mean empathy score among medical students was 102.73 with SD = 12.64. Multiple regression analysis revealed that, “age,” “perception of the importance of empathy,” “academic pressure,” “desire to be a doctor after graduation,” and “self-esteem” were significant predictors of empathy ( P < 0.05) and the adjusted R 2 was 0.462. The correlation matrix between empathy and self-esteem was significant ( r = 0.510, P < 0.01). Self-esteem explained 15.5% of the variation of empathy in the final regression model. Conclusion There was a positive association between self-esteem and empathy. Self-esteem is one of many factors which contribute to medical students’ empathy. Age, academic pressure, attitude toward empathy and future career also play a critical role in medical student empathy. Enhancing medical students’ self-esteem may be an efficacious way to improve medical students’ empathy.