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.

A circRNA–miRNA–mRNA network analysis underlying pathogenesis of human heart failure

BACKGROUND The molecular mechanisms of heart failure(HF) are still poorly understood. Circular RNA(circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF.METHODS & RESULTS We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs(DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-mi RNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10m RNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively.CONCLUSION These findings demonstrated circRNAs have species and tissue specific expression patterns;while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.

Heart valve disease in elderly Chinese population： effect of advanced age and comorbidities on treatment decision-making and outcomes

Background A considerable proportion of elderly patients with symptomatic severe heart valve disease are treated conservatively de- spite clear indications for surgical intervention. However, little is known about how advanced age and comorbidities affect treatment deci-sion-making and therapeutic outcomes. Methods Patients （n = 234, mean age： 78.5 ± 3.7 years） with symptomatic severe heart valve dis- ease hospitalized in our center were included. One hundred and fifty-one patients （65%） were treated surgically （surgical group） and 83 （35%） were treated conservatively （conservative group）. Factors that affected therapeutic decision-making and treatment outcomes were investi- gated and long-term survival was explored. Results Isolated aortic valve disease, female sex, chronic renal insufficiency, aged _〉 80 years, pneumonia, and emergent status were independent factors associated with therapeutic decision-making. In-hospital mortality for the surgical group was 5.3% （8/151）. Three patients （3.6%） in the conservative group died during initial hospitalization. Low cardiac output syndrome and chronic renal insufficiency were identified as predictors of in-hospital mortality in the surgical group. Conservative treatment was identi- fied as the single risk factor for late death in the entire study population. The surgical group had better 5-year （77.2% vs. 45.4%, P 〈 0.0001） and 10-year （34.5% vs. 8.9%, P 〈 0.0001） survival rates than the conservative group, even when adjusted by propensity score-matched analysis. Conclusions Advanced age and geriatric comorbidities profoundly affect treatment decision-making for severe heart valve disease. Valve surgery in the elderly was not only safe but was also associated with good long-term survival while conservative treatment was unfavorable for patients with symptomatic severe valve disease.

Heart rate-adjusted PR as a prognostic marker of long-term ventricular arrhythmias and cardiac death in ICD/CRT-D recipients

Objective To evaluate the PR to RR interval ratio (PR/RR,heart rate-adjusted PR) as a prognostic marker for long-term ventricular arrhythmias and cardiac death in patients with implantable cardioverter defibrillator (ICDs) and cardiac resynchronization therapy with defibrillators (CRT-D).Methods We retrospectively analyzed data from 428 patients who had an ICD/CRT-D equipped with home monitoring.Baseline PR and RR interval data prior to ICD/CRT-D implantation were collected from standard 12-lead electrocardiograph,and the PR/RR was calculated.The primary endpoint was appropriate ICD/CRT-D treatment of ventricular arrhythmias (VAs),and the secondary endpoint was cardiac death.Results During a mean follow-up period of 38.8 ± 10.6 months,197 patients (46%) experienced VAs,and 47 patients (11%) experienced cardiac death.The overall PR interval was 160 ± 40 ms,and the RR interval was 866 ± 124 ms.Based on the receiver operating characteristic curve,a cut-off value of 18.5% for the PR/RR was identified to predict VAs.A PR/RR ≥ 18.5% was associated with an increased risk of VAs [hazard ratio (HR)= 2.243,95% confidence interval (CI)= 1.665–3.022,P < 0.001) and cardiac death (HR = 2.358,95%CI = 1.240–4.483,P = 0.009) in an unadjusted analysis.After adjustment in a multivariate Cox model,the relationship remained significant among PR/RR ≥ 18.5%,VAs (HR = 2.230,95%CI = 1.555–2.825,P < 0.001) and cardiac death (HR = 2.105,95%CI = 1.101–4.025,P = 0.024.Conclusions A PR/RR ≥ 18.5% at baseline can serve as a predictor of future VAs and cardiac death in ICD/CRT-D recipients.

The value of serum metabolomics analysis in predicting the response to cardiac resynchronization therapy

Objective To construct a prediction model based on metabolic profiling for predicting the response to cardiac resynchronization therapy(CRT).Methods Peripheral venous(PV)and coronary sinus(CS)blood samples were collected from 25 patients with heart failure(HF)at the time of CRT implantation,and PV blood samples were obtained from ten healthy controls.The serum samples were analyzed by liquid chromatography-mass spectrometry(LC-MS).As per the clinical and echocardiographic assessment at the 6-month follow-up,the HF patients were categorized as CRT responders and non-responders.Results HF patients had altered serum metabolomic profiles that were significantly different from those of the healthy controls.Differential metabolites were also observed between CRT responders and non-responders.A prediction model for CRT response(CRT-Re)was constructed using the concentration levels of the differential metabolites,L-arginine and taurine.The optimal cutoff value of the CRT-Re model was found to be 0.343 by ROC analysis(sensitivity,88.2%;specificity,87.5%;Area under curve(AUC)=0.897,P=0.002).The concentration levels of the differential metabolites,L-arginine and lysyl-gamma-glutamate,in PV serum were significantly correlated with that in CS serum(r=0.945 and 0.680,respectively,all P<0.001).Conclusions Our results suggest that serum-based metabolic profiling may be a potential complementary screening tool for predicting the outcome of CRT.

Nonhypertensive male with multiple paragangliomas of the heart and neck:A case report

BACKGROUND Paraganglioma is a rare disease that can be lethal if undiagnosed.Thus,quick recognition is very important.Cardiac paragangliomas are found in patients who have hypertension.The classic symptoms are the triad of headaches,palpitations,and profuse sweating.We describe a very rare case of multiple paragangliomas of the heart and bilateral carotid artery without hypertension and outline the management strategies for this disease.CASE SUMMARY A 46-year-old man presented with the chief complaint of recently recurrent chest pain with a history of hemangioma of the bilateral carotid artery that had been surgically removed.He was found to have an intracardiac mass in the right atrioventricular groove and underwent successful excision.The final pathology demonstrated that the intracardiac mass was a cardiac paraganglioma,and the patient had an increased level of normetanephrine in the blood.The pathology and immunohistochemistry results showed that the bilateral carotid masses were also paragangliomas.During the 3 mo follow-up period,the patient did not experience recurrence of chest pain.CONCLUSION To our knowledge,this is the first case of multiple paragangliomas of the heart and neck without hypertension.This rare disease can be lethal if left undiagnosed.Thus,quick recognition is very important.The key to the diagnosis of cardiac paraganglioma is the presence of typical symptoms,including headaches,palpitations,profuse sweating,hypertension,and chest pain.Radiology can demonstrate the intracardiac mass.It is important to determine the levels of normetanephrine in the blood.The detection of genetic mutations is also recommended.Surgical resection is necessary to treat the disease and obtain pathological evidence.

An unexpected electrocardiogram sign of subacute left ventricular free wall rupture: Its early awareness may be lifesaving

BACKGROUND:Post-infarct left ventricular free wall rupture(LVFWR)is not always an immediately catastrophic complication.The rupture can be subacute,allowing time for diagnosis and intervention.Accordingly,early recognition of the entity may be lifesaving.METHODS:We present an electrocardiogram(ECG)change pattern in two cases,which was erroneously attributed to ischemia.Two women in their 80s were admitted to our institute after experiencing the sudden onset of chest pain.They were managed as anterior ST-segment elevation myocardial infarction without reperfusion treatment.Unfortunately,they experienced a recurrence of severe chest pain with cardiogenic shock during hospitalisation.The ECG recorded at that time showed a ST-segment re-elevation in infract-related leads.RESULTS:The two cases were regrettably received a misjudgement of reinfarction at first,and one of the patients even was administrated with tirofi ban.Afterwards the diagnosis of subacute LVFWR was made through antemortem echocardiography.CONCLUSION:New ST-segment elevation(STE)in infarct-associated leads,coupled with recurrence of chest pain and new-onset hypotension,may constitute the premonitory signs of a subacute LVFWR.

Transmesosigmoid hernia:Case report and review of literature

Transmesosigmoid hernia has previously been considered as a rare condition.The clinical symptoms can be nonspecific.Here,we report a case of acute intestinal obstruction because of transmesosigmoid hernia.In addition,after a comprehensive review of PubMed and China National Knowledge Infrastructure,we present a review of 22 cases of transmesosigmoid hernia.We summarize several valuable clinical features that help early recognition of transmesosigmoid hernia.As a result of easy strangulation,in patients without a history of surgery or abdominal inflammation who present with symptoms of progressive or persistent small bowel obstruction(SBO),surgeons should consider the possibility of transmesosigmoid hernia.In addition,based on our data,in patients with SBO because of transmesosigmoid hernia,the defect is usually 2-5 cm in diameter.Furthermore,because of the high risk of strangulation with transmesosigmoid hernia,it is mandatory to reassess the condition timely and periodically when patients receive conservative treatment.

EFFECTS OF THE HOE 694 ON TRANSIENT INWARD CURRENT AND NA^+- CA^(2+) EXCHANGE IN GUINEA PIG CARDIOMYOCYTES

To determine the effects of HOE 694, a new and potent Na＋- H＋ exchanger blocker, on transient inward current (Iti) and Na＋- Ca2＋ exchange during hypoxia- reoxygenation in guinea pig cardiomyocytes. Methods. Cardiomyocytes were isolated from adult guinea pig ventricle. Experiment was performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure. The cells were subjected to hypoxia and reoxygenation. The ionic currents were studied with patch clamp technique. Results. In the absence of HOE 694, hypoxia- reoxygenation induced Iti in 12 of 15 experiments; but in cardiomyocytes pretreated with HOE 694 (10～ 50μ mol/L), the incidence of Iti observed during reoxygenation was reduced to 5 of 11 experiments and 3 of 10 experiments, P Conclusions. Blockade of the Na＋- H＋ exchange by HOE 694 could reduce Ca2＋ overload upon hypoxia- reoxygenation, and inhibition of Na＋- H＋ exchange may also indirectly decrease Na＋- Ca2＋ exchange activity during hypoxia.

Association of time-varying changes in physical activity with cardiac death and all-cause mortality after ICD or CRT-D implantation

OBJECTIVE To evaluate the association of longitudinal changes in physical activity(PA)with long-term outcomes after im-plantable cardioverter-defibrillator(ICD)or cardiac resynchronization therapy defibrillator(CRT-D)implantation.METHODS Patients with ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed.Accelerometer-de-rived PA changes over 12 months post implantation were obtained from the archived home monitoring data.The primary end-points were cardiac death and all-cause mortality.The secondary endpoints were the first ventricular arrthymia(VA)and first ap-propriate ICD shock.RESULTS In 705 patients,446(63.3%)patients showed improved PA over 12 months after implantation.During a mean 61.5-month follow-up duration,99 cardiac deaths(14.0%)and 153 all-cause deaths(21.7%)occurred.Compared to reduced/un-changed PA,improved PA over 12 months could result in significantly reduced risks of cardiac death(improved PA≤30 min:hazard ratio(HR)=0.494,95%CI:0.288−0.848;>30 min:HR=0.390,95%CI:0.235−0.648)and all-cause mortality(improved PA≤30 min:HR=0.467,95%CI:0.299−0.728;>30 min:HR=0.451,95%CI:0.304−0.669).No differences in the VAs or ICD shocks were observed across different groups of PA changes.PA changes can predict the risks of cardiac death only in the low baseline PA group,but improved PA was associated with 56.7%,57.4%,and 62.3%reduced risks of all-cause mortality in the low,moderate,and high baseline PA groups,respectively,than reduced/unchanged PA.CONCLUSIONS Improved PA could protect aganist cardiac death and all-cause mortality,probably reflecting better clinical efficacy after ICD/CRT-D implantation.Low-intensity exercise training might be encouraged among patients with different baseline PA levels.

Activation of histamine/H R signaling pathway promotes cardiac differentiation and maturation of human induced pluripotent stem cells

The efficiency and quality of human induced pluripotent stem cell-derived cardiomyocytes(hiPSC CMs)is crucial for regenerative medicine,disease modeling,drug screening and the study of the development events during cardiac specification.However,their applications have been hampered by the differentiation efficiency,poor maturation and high interline variability.Recent studies have reported that histamine plays important roles in hema topoietic stem cell proliferation and neutrophil maturation.However,its roles in cardiovascular tissue regeneration have not been thoroughly investigated.In the current study,we identified a novel physiological function of the histamine/histamine 1 receptor(H,R)signal in regulating the differentiation of hiPSC-CMs and heart development.

The role of OR51E2 in colon cancer and rectal adenocarcinoma and the potential underlying mechanism

Objective Short-chain fatty acids(SCFAs)produced by intestinal microbiota influence the pathogenesis and development of several intestinal diseases.OR51E2 is a newly discovered SCFA receptor.At present,research on the link between OR51E2 and intestinal cancer is limited.This study aimed to analyze the relationship between OR51E2 and colorectal cancer.Methods Bioinformatic analysis revealed the OR51E2 protein expression pattern in different parts of the intestine,regulation of related proteins,and immune cell infiltration.The expression pattern and prognostic value of OR51E2 in colon and rectal cancer was determined,and the miRNAs targeting OR51E2 were predicted.Results The expression level of OR51E2 was relatively high in the colon,small intestine,and duodenum.In addition,OR51E2 expression level was significantly reduced in colon and rectal cancer.A positive correlation between OR51E2 and immune cells was observed,which was associated with the survival of patients with colon and rectal cancer(hazard ratio:1.5).Further,miR-96-5p and miR-1271-5-p were predicted to target OR51E2.Conclusion OR51E2 plays an important positive role in the survival of patients with colon cancer and rectal adenocarcinoma.

Successful left-sided accessory pathway ablation without reference catheter in patient with atresia of coronary sinus and thin persistent left superior vena cava

We report a case of atrioventricular reentrant tachycardia (AVRT) with ostial atresia of the coronary sinus (CS). Without the anatomic angiography, radiofrequency (RF) energy was applied at the mitral valve annulus and the bypass tract was eliminated. After the therapy procedure, by CS angiography, we knew the persistent left superior vena cava (PLSVC), and the coronary sinus was connected with vena cava superior, very thin in a diameter. The therapy procedure was successful. The patient has remained completely symptom free.

The critical roles of m6A modification in metabolic abnormality and cardiovascular diseases

N6-methyladenosine(m6A)RNA methylation is an emerging area of epigenetics,which is a reversible and dynamic modification mediating by‘writers’(methylase,adding methyl groups,METTL3,METTL14,and WTAP),‘erasers’(demethylase,deleting methyl groups,FTO and ALKBH5),and‘readers’(YTHDF1-3,YTHDC1 and YTHDC2).Recent studies in human,animal models and cell levels have disclosed a critical role of m6A modification in regulating the homeostasis of metabolic processes and cardiovascular function.Evidence from these studies identify m6A as a candidate of biomarker and therapeutic target for metabolic abnormality and cardiovascular diseases(CVD).Comprehensive understanding of the complexity of m6A regulation in metabolic diseases and CVD will be helpful for us to understand the pathogenesis of CVD.In this review,we discuss the regulatory role of m6A in metabolic abnormality and CVD.We will emphasize the clinical relevance of m6A dysregulation in CVD.

The effects of nicotinamide adenine dinucleotide in cardiovascular diseases: Molecular mechanisms, roles and therapeutic potential

Recently, cardiovascular diseases (CVDs) were identified as the leading cause of mortality, imposing a heavy burden on health care systems and the social economy. Nicotinamide adenine dinucleotide (NAD+), as a pivotal co-substrate for a range of different enzymes, is involved in many signal transduction pathways activated in CVDs. Emerging evidence has shown that NAD+ can exert remediating effects on CVDs by regulating metabolism, maintaining redox homeostasis and modulating the immune response. In fact, NAD+ might delay ageing through sirtuin and non-sirtuin pathways and thus contribute to interventions for age-related diseases such as CVDs. Considering that robust clinical studies of NAD+ are ongoing, we discuss current challenges and the future translational potential of NAD+ based on existing studies and our understanding. Despite some remaining gaps in its clinical application, NAD+ has been shown to have broad prospects and pan-effects, making it a suitable prophylactic drug for CVDs.

Impact of the gut microbiome on atherosclerosis

Atherosclerosis is a chronic inflammatory metabolic disease with a complex pathogenesis.However,the exact details of its pathogenesis are still unclear,which limits effective clinical treatment of atherosclerosis.Recently,multiple studies have demonstrated that the gut microbiota plays a pivotal role in the onset and progression of atherosclerosis.This review discusses possible treatments for atherosclerosis using the gut microbiome as an intervention target and summarizes the role of the gut microbiome and its metabolites in the development of atherosclerosis.New strategies for the treatment of atherosclerosis are needed.This review provides clues for further research on the mechanisms of the relationship between the gut microbiota and atherosclerosis.

Substrate and Functional Diversity of Protein Lysine Post-translational Modifica

Lysine post-translational modifications(PTMs)are widespread and versatile protein PTMs that are involved in diverse biological processes by regulating the fundamental functions of histone and non-histone proteins.Dysregulation of lysine PTMs is implicated in many diseases,and targeting lysine PTM regulatory factors,including writers,erasers,and readers,has become an effective strategy for disease therapy.The continuing development of mass spectrometry(MS)technologies coupled with antibody-based affinity enrichment technologies greatly promotes the discovery and decoding of PTMs.The global characterization of lysine PTMs is crucial for deciphering the regulatory networks,molecular functions,and mechanisms of action of lysine PTMs.In this review,we focus on lysine PTMs,and provide a summary of the regulatory enzymes of diverse lysine PTMs and the proteomics advances in lysine PTMs by MS technologies.We also discuss the types and biological functions of lysine PTM crosstalks on histone and non-histone proteins and current druggable targets of lysine PTM regulatory factors for disease therapy.

GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases

Partial endothelial-to-mesenchymal transition(EndMT)is an intermediate phenotype observed in endothelial cells(ECs)undergoing a transition toward a mesenchymal state to support neovascularization during(patho)physiological angiogenesis.Here,we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4(GTF2H4)as a positive regulator of this process.In addition,we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3(ERCC3)to co-regulate partial EndMT.Furthermore,by using phosphorylation proteomics and site-directed mutagenesis,we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3(NCOA3)at serine 1330,which promoted the interaction between NCOA3 and p65,resulting in the transcriptional activation of NF-κB and the NF-kB/Snail signaling axis during partial EndMT.In vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic injury.Collectively,our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.

Six-month clinical outcomes of Firebird 2TM sirolimus-eluting stent implantation in real-world patients with coronary artery diseases

Background The Firebird 2TM sirolimus-eluting stent （Firebird 2 stent） is a second-generation sirolimus-eluting stent which has a cobalt-chromium alloy stent platform, a brand new bracket structure, and two layers of styrene-butylenes-styrene polymer coatings with better biocompatibility. The Firebird 2TM cObalt-Chromium alloy sirolimus-elUting Stent registry （FOCUS registry） aimed to evaluate the safety and efficacy of the Firebird 2 stent in patients with coronary artery disease in daily practice.Methods The FOCUS registry is a prospective, non-randomized, international multi-center, single-arm clinical registry.Between March 2009 and February 2010, 5084 patients receiving at least 1 Firebird 2 stent during daily clinical practice at 83 medical centers were enrolled.Results Of the 5084 patients enrolled in the registry, 5077 and 5058 were respectively available for 30 days and 6 months follow-up. The 30-day rate of major adverse cardiac events （MACE） was 1.20%, including 13 cardiac deaths, 46 non-fatal myocardial infarction （MI）, and 6 target vessel revascularization （TVR）. At 6 months follow-up, the rate of MACE was 1.80%. There were 32 cardiac deaths, 48 non-fatal MI, and 15 TVR. According to the Academic Research Consortium definition, definite/probable stent thrombosis （ST） occurred in 0.43% （22/5058） of patients, including 8 cases of acute ST, 11 subacute ST, and 3 late ST.Conclusion The Firebird 2 stent showed the promising efficacy and safety at 30 days and 6 months in a real-world population of patients with coronary artery diseases.