Virtual reality-based cognitive-behavioural therapy for the treatment of anxiety in patients with acute myocardial infarction:a randomised clinical trial

Background The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction(AMI),significantly disrupting their recovery.Providing timely and easily accessible psychological interventions using virtual reality-based cognitive-behavioural therapy(VR-CBT)could potentially improve both acute and long-term symptoms affecting their mental health.Aims We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit(ICU)during the acute stage of their illness.Methods In this single-blind randomised clinical trial,participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February 2023.Patients who were Han Chinese aged 18-75 years were randomly assigned(1:1)via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support,or the control group to receive standard mental health support only.VR-CBT consisted of four modules and was delivered at the bedside over a 1-week period.Assessments were done at baseline,immediately after treatment and at 3-month follow-up.The intention-to-treat analysis began in June 2023.The primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale(HAM-A).Results Among 148 randomised participants,70 were assigned to the VR-CBT group and 78 to the control group.The 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention(Cohen’s d=−1.27(95%confidence interval(CI):−1.64 to−0.90,p<0.001)and 3-month follow-up(Cohen’s d=−0.37(95%CI:−0.72 to−0.01,p=0.024).Of the 70 participants who received VR-CBT,62(88.6%)completed the entire intervention.Cybersickness was the main reported adverse event(n=5).Conclusions Our results indicate that VR-CBT can significantly reduce post-AMI anxiety at the acute stage of the illness;the improvement was maintained at the 3-month follow-up.Trial registration number The trial was registered at www.chictr.org.cn with the identifier:ChiCTR2200066435.

Targeting deubiquitinase OTUB1 protects vascular smooth muscle cells in atherosclerosis by modulating PDGFRβ

Atherosclerosis is a chronic artery disease that causes various types of cardiovascular dysfunction.Vascular smooth muscle cells(VSMCs),the main components of atherosclerotic plaque,switch from contractile to synthetic phenotypes during atherogenesis.Ubiquitylation is crucial in regulating VSMC phenotypes in atherosclerosis,and it can be reversely regulated by deubiquitinases.However,the specific effects of deubiquitinases on atherosclerosis have not been thoroughly elucidated.In this study,RNAi screening in human aortic smooth muscle cells was performed to explore the effects of OTU family deubiquitinases,which revealed that silencing OTUB1 inhibited PDGF-BB-stimulated VSMC phenotype switch.Further in vivo studies using Apoe−/−mice revealed that knockdown of OTUB1 in VSMCs alleviated atherosclerosis plaque burden in the advanced stage and led to a stable plaque phenotype.Moreover,VSMC proliferation and migration upon PDGF-BB stimulation could be inhibited by silencing OTUB1 in vitro.Unbiased RNA-sequencing data indicated that knocking down OTUB1 influenced VSMC differentiation,adhesion,and proliferation.Mass spectrometry of ubiquitinated protein confirmed that proteins related to cell growth and migration were differentially ubiquitylated.Mechanistically,we found that OTUB1 recognized the K707 residue ubiquitylation of PDGFRβwith its catalytic triad,thereby reducing the K48-linked ubiquitylation of PDGFRβ.Inhibiting OTUB1 in VSMCs could promote PDGFRβdegradation via the ubiquitin–proteasome pathway,so it was beneficial in preventing VSMCs’phenotype switch.These findings revealed that knocking down OTUB1 ameliorated VSMCs’phenotype switch and atherosclerosis progression,indicating that OTUB1 could be a valuable translational therapeutic target in the future.

Early initiation of ARBs without blood pressure risk via neutrophil membrane-fused pH-sensitive liposomes to reduce cardiomyocyte apoptosis after acute myocardial infarction

Activation of the local renin-angiotensin system(RAS)promotes cardiomyocyte apoptosis and cardiac remodeling after acute myocardial infarction(AMI).As an anti-RAS drug,the effect of Valsartan in the early stage of acute MI is limited by its low drug concentration in the heart and low dosage.Here,by exploiting the inherent nature of neutrophils migrating to the injured myocardium and the local low-pH microenvironment caused by ischemia and hypoxia after myocardial infarction,we designed nanocarrier(NSLP)-hybridized neutrophil membranes and pH-sensitive liposomes(SLPs)for the delivery of Valsartan(NSLPVal).These functional nanocarriers could mimic neutrophils and are homed to the injured heart;they were also found to respond to a low-pH microenvironment.In the mouse model of MI,we found that NSLP-Val could target the infarct marginal zone and release Valsartan locally in the low-pH microenvironment without affecting hemodynamic stability.Further,locally released angiotensin receptor inhibitors reduced the infarct size and inflammatory response by inhibiting cardiomyocytes.Ultimately,NSLP-Val improved cardiac function and inhibited cardiac hypertrophy and fibrosis.

Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines.Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules.Here,we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR,fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles(MSNs)loaded with microRNA-10b.The hybrid membrane could endow nanoparticles with strong capacity to migrate into infammatory sites and neutralize proinfammatory cytokines and increase the delivery efficiency of microRNA-1Ob into adult mammalian cardiomyocytes(CMs)by fusing with cell membranes and leading to the release of MSNs-miR into cytosol.Upon NM@miR administration,this nanoparticle could home to the injured myocardium,restore the local immunity,and efficiently deliver microRNA-1Ob to cardiomyocytes,which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-1Ob.This combination therapy could finally improve cardiac function and mitigate ventricular remodeling.Consequently,this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

Active greeting technique: a mother-and-child catheter based technique to facilitate retrograde wire externalization in recanalization of coronary chronic total occlusion

Although retrograde approach has greatly improved the success rate of percutaneous coronary intervention(PCI) for coronary chronic total occlusion(CTO), retrograde wire externalization still remains challenging and time-consuming in some cases. Cases utilizing ‘‘Active Greeting Technique(AGT)", a mother-and-child catheter based technique to facilitate retrograde wire externalization, were extracted from Chronic Total Occlusion Club, China(CTOCC) database. AGT was performed by deep intubation a mother-and-child catheter(GuidezillaTMextension, 4 or 5 Fr inner catheter, and etc.) in combination with either reverse controlled antegrade or retrograde subintimal tracking(CART) technique or retrograde wire crossing technique. A total of 111 patients with 112 CTO lesions treated with this technique were retrospectively analyzed. Reverse CART technique and retrograde wire crossing technique were performed in 90.2% and 9.8% of all procedures. The utilization of GuidezillaTMextension, 4 Fr, and 5 Fr inner catheter accounted for 94.6%, 3.6%, and 1.8%, respectively. Externalization of retrograde wire was successful in all cases. No procedural complications were adjudicated to AGT. Complications independent of AGT included two target vessel perforations and two collateral perforations. No in-hospital major adverse cardiac events were found. AGT is a feasible and safe technique that facilitates retrograde wire externalization.