Aims: Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated.Methods: Twenty‐four C57BL/6J mice were divided into four groups: a control group; a risperidone‐treated group; a lorcaserin‐treated group; and a combined risperidone + lorcaserin‐treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes post‐treatment for determination of c‐fos activity. In addition, brains of NPY‐GFP mice treated with or without risperidone were collected to perform colocalization of NPY and c‐fos, as well as NPY and 5‐HT2c receptor using immunohistochemistry.Results: There was significantly elevated c‐fos expression in the hypothalamic arcuate nucleus (Arc) of risperidone‐treated mice. More than 68% c‐fos‐positive neurons were NPY‐expressing neurons. Furthermore, in situ hybridization revealed that Arc NPY mRNA expression was significantly increased in the risperidone‐treated group compared with control group. Moreover, we identified that 95% 5‐HT2c receptors were colocalized with NPY positive neurons, and increased Arc NPY mRNA expression induced by risperidone was markedly reduced by cotreatment with lorcaserin, a specific 5‐HT2c receptor agonist.Conclusion: Our findings provide critical insight into the mechanisms underlying antipsychotic‐induced obesity, which may assist the development of therapeutic strategies to address metabolic side effects of risperidone.

The Orsiro biodegradable polymer sirolimus-eluting stent (O-SES) is a new-generation biodegradable polymer drug-eluting stent with the thinnest strut thickness to date developed to improve the percutaneous treatment of patients with coronary artery disease. We perform a meta-analysis of randomized clinical trials (RCTs) comparing the efficacy and safety of an ultra-thin, Orsiro biodegradable polymer sirolimus-eluting stent (O-SES) compared with durable polymer drug-eluting stents (DP-DESs). Medline, Embase, and CENTRAL databases were searched for randomized controlled trials comparing the safety and efficacy of O-SES versus DP-DES. Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. We used the Mantel-Haenszel method to calculate risk ratio (RR) by means of a random-effects model. Six RCTs with a total of 6949 patients were selected. All included trials were rated as low risk of bias. The O-SES significantly reduced the risk of myocardial infarction (RR 0.78, 95% confidence interval [CI] 0.62–0.98; I2 = 0%; 10 fewer per 1000 [from 1 fewer to 18 fewer]; high quality) compared with the DP-DES. There was no significant difference between O-SES and DP-DES in the prevention of stent thrombosis (RR: 0.75; 95% CI: 0.52–1.08), cardiac death (RR: 0.93; 95% CI: 0.63–1.36), target lesion revascularization (RR 1.10, 95% CI 0.86–1.42) and target vessel revascularization (RR 0.97, 95% CI 0.78–1.21). Among patients undergoing percutaneous coronary intervention, O-SES resulted in significantly lower rates of myocardial infarction than DP-DES and had a trend toward reduction in stent thrombosis.

Melanoma is the most lethal cutaneous malignancy that threatens human lives. Poor sensitivity to chemotherapy drugs and the high rate of resistance are the bottlenecks of melanoma treatment. Thus, new chemotherapy drugs are needed. Drug repurposing is a safe, economical and timesaving way to explore new chemotherapy for diseases. Here, we investigated the possibility of repurposing the antibiotic monensin as an anti-melanoma agent. Using three human melanoma cells and two nomal human cell lines as cell models, we found that monensin is obviously toxic to human melanoma cells while safe to nomal human cells. It effectively inhibited cell proliferation and viability, while promoted apoptosis and differentiation of human melanoma cells in vitro. By establishment of an animal model of transplanted human melanoma in nude mice, we demonstrated that monensin suppressed the growth of xenografts in vivo. At the same time, we found that melanogenesis increased and the ability of sphere and cloning forming of melanoma decreased under the treatment of monensin. Further detection about differentiation and pluripotent regulations were executed. Our results suggest that monensin is a potent inhibitor of melanoma, and its anti-tumor mechanism may be through promoting the final differentiation of melanoma stem cells and inhibiting their stemness maintenance.

Purpose: This study investigated possible mechanism of left atrial appendage (LAA) thrombosis and constructed a model to evaluate the future risk of LAA thrombosis and spontaneous echo contrast (SEC) in non-valvular atrial fibrillation (NVAF) patients. Methods: This retrospective study included 2591 patients diagnosed with NVAF. Patients were divided based on the presence of transesophageal echocardiography (TEE) into a thrombus group, SEC group, and control group. General, biochemical, and echocardiography data of the three groups were analyzed. The variables independently associated with LAA thrombosis and SEC were determined by the logistic regression analysis. A nomogram was constituted based on the regression analysis and the discriminatory ability was analyzed by receiver operating characteristic (ROC) curve. Results: LAA thrombosis and SEC were present in 110 (4.2%) patients and 103 (3.9%) patients, respectively. AF type (OR = 1.857), previous stroke (OR = 1.924), fibrinogen (OR = 1.636), diameters of the left atria (OR = 1.094), left ventricular ejection fraction (OR = 0.938), and LAA maximum caliber (OR = 1.238) resulted as independent risk factors for LAA thrombosis and SEC. The area under curve of the nomogram established by multivariate logistic regression was 0.824. Conclusions; Through the study, 6 independent risk factors related to the LAA thrombosis and SEC were found, and an effective nomogram was constructed to predict the LAA thrombosis and SEC in NVAF patients.

Objective To investigate the correlation between the heparin dose and activated clotting time (ACT) during left atrial appendage occlusion (LAAC) in patients with non-valvular atrial fibrillation (NVAF) under different antithrombotic management backgrounds and to provide evidence for the rational use of heparin in LAAC. Methods Patients with NVAF who underwent LAAC in our hospital from February 2017 to March 2021 were evaluated. The patients were grouped according to the type of antithrombotic therapy they received before LAAC and the international normalised ratio (INR) into the following groups: patients on antiplatelet drugs, patients on non-vitamin K antagonist oral anticoagulants, patients with a warfarin INR < 1.8, and patients with a warfarin INR ≥ 1.8. The heparin doses were 100, 100, 100, and 80 U/kg, respectively. To measure ACT, venous blood samples were collected at 15 minutes after administering the drug. Results The study enrolled 435 patients, comprising 135, 155, 107, and 78 in the antiplatelet drug, non-vitamin K antagonist oral anticoagulant, warfarin INR < 1.8, and, warfarin INR ≥ 1.8 groups, respectively. At baseline, the proportion of patients with coronary heart disease was significantly lower in the warfarin INR < 1.8 group than in the other three groups (p < 0.01), while there were no significant differences in other parameters among the groups (p > 0.05). The heparin dose was significantly lower in the warfarin INR ≥ 1.8 group (80.25 ± 2.84 U/kg) than in the other three groups (p < 0.001). There was no significant difference in the ACT among the four groups (p > 0.05). LAAC was completed in all 435 patients without perioperative bleeding or thromboembolic complications. Conclusions For patients not taking warfarin or with an INR < 1.8 on warfarin before LAAC, it is reasonable to use heparin at a dose of 100 U/kg. It is safe and effective to reduce the heparin dose by 20% in patients with an INR ≥ 1.8.