Unraveling brain aging through the lens of oral microbiota

The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia

BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

Who can benefit more from its twelve-week treatment:A prospective cohort study of blonanserin for patients with schizophrenia

BACKGROUND Blonanserin(BNS)is a well-tolerated and effective drug for treating schizophrenia.AIM To investigate which types of patients would obtain the most benefit from BNS treatment.METHODS A total of 3306 participants were evaluated in a 12-week,prospective,multicenter,open-label post-marketing surveillance study of BNS.Brief psychiatric rating scale(BPRS)scores were calculated to evaluate the effectiveness of BNS,and its safety was assessed with the incidence of adverse drug reactions.Linear regression was used to screen the influencing factors for the reduction of BPRS total score,and logistic regression was used to identify patients with a better response to BNS.RESULTS The baseline BPRS total score(48.8±15.03)decreased to 27.7±10.08 at 12 weeks(P<0.001).Extrapyramidal symptoms(14.6%)were found to be the most frequent adverse drug reactions.The acute phase,baseline BPRS total score,current episode duration,number of previous episodes,dose of concomitant antipsychotics,and number of types of sedative-hypnotic agents were found to be independent factors affecting the reduction of BPRS total score after treatment initiation.Specifically,patients in the acute phase with baseline BPRS total score≥45,current episode duration<3 months,and≤3 previous episodes derived greater benefit from 12-week treatment with BNS.CONCLUSION Patients in the acute phase with more severe symptoms,shorter current episode duration,fewer previous episodes,and a lower psychotropic drug load derived the greatest benefit from treatment with BNS.

Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of GABAergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

The solute carrier transporters and the brain:Physiological and pharmacological implications

Solute carriers(SLCs)are the largest family of transmembrane transporters that determine the exchange of various substances,including nutrients,ions,metabolites,and drugs across biological membranes.To date,the presence of about 287 SLC genes have been identified in the brain,among which mutations or the resultant dysfunctions of 71 SLC genes have been reported to be correlated with human brain disorders.Although increasing interest in SLCs have focused on drug development,SLCs are currently still under-explored as drug targets,especially in the brain.We summarize the main substrates and functions of SLCs that are expressed in the brain,with an emphasis on selected SLCs that are important physiologically,pathologically,and pharmacologically in the blood-brain barrier,astrocytes,and neurons.Evidence suggests that a fraction of SLCs are regulated along with the occurrences of brain disorders,among which epilepsy,neurodegenerative diseases,and autism are representative.Given the review of SLCs involved in the onset and procession of brain disorders,we hope these SLCs will be screened as promising drug targets to improve drug delivery to the brain.

MonkeyTrail:A scalable video-based method for tracking macaque movement trajectory in daily living cages

Behavioral analysis of macaques provides important experimental evidence in the field of neuroscience.In recent years,video-based automatic animal behavior analysis has received widespread attention.However,methods capable of extracting and analyzing daily movement trajectories of macaques in their daily living cages remain underdeveloped,with previous approaches usually requiring specific environments to reduce interference from occlusion or environmental change.Here,we introduce a novel method,called MonkeyTrail,which satisfies the above requirements by frequently generating virtual empty backgrounds and using background subtraction to accurately obtain the foreground of moving animals.The empty background is generated by combining the frame difference method(FDM)and deep learning-based model(YOLOv5).The entire setup can be operated with low-cost hardware and can be applied to the daily living environments of individually caged macaques.To test MonkeyTrail performance,we labeled a dataset containing>8000 video frames with the bounding boxes of macaques under various conditions as ground-truth.Results showed that the tracking accuracy and stability of MonkeyTrail exceeded that of two deep learningbased methods(YOLOv5 and Single-Shot MultiBox Detector),traditional frame difference method,and na?ve background subtraction method.Using MonkeyTrail to analyze long-term surveillance video recordings,we successfully assessed changes in animal behavior in terms of movement amount and spatial preference.Thus,these findings demonstrate that MonkeyTrail enables low-cost,large-scale daily behavioral analysis of macaques.

Angiogenesis in hepatocellular carcinoma:mechanisms and anti-angiogenic therapies

Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-associated death worldwide.Angiogenesis,the process of formation of new blood vessels,is required for cancer cells to obtain nutrients and oxygen.HCC is a typical hypervascular solid tumor with an aberrant vascular network and angiogenesis that contribute to its growth,progression,invasion,and metastasis.Current anti-angiogenic therapies target mainly tyrosine kinases,vascular endothelial growth factor receptor(VEGFR),and plateletderived growth factor receptor(PDGFR),and are considered effective strategies for HCC,particularly advanced HCC.However,because the survival benefits conferred by these anti-angiogenic therapies are modest,new anti-angiogenic targets must be identified.Several recent studies have determined the underlying molecular mechanisms,including pro-angiogenic factors secreted by HCC cells,the tumor microenvironment,and cancer stem cells.In this review,we summarize the roles of pro-angiogenic factors;the involvement of endothelial cells,hepatic stellate cells,tumor-associated macrophages,and tumor-associated neutrophils present in the tumor microenvironment;and the regulatory influence of cancer stem cells on angiogenesis in HCC.Furthermore,we discuss some of the clinically approved anti-angiogenic therapies and potential novel therapeutic targets for angiogenesis in HCC.A better understanding of the mechanisms underlying angiogenesis may lead to the development of more optimized anti-angiogenic treatment modalities for HCC.

The Psychosomatic Traits of“People with the Five Elements in Traditional Chinese Medicine”:A Qualitative Study

Objective To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of“people with the five elements in traditional Chinese medicine(TCM).”Methods Data collected from the literature review,two sessions of brainstorming of experts with related experience in“people with the five elements in TCM”from October 2020 to December 2020,and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed.Triangulation was used in this study,and theming and synthesizing were used to analyze the data.Results A total of 31 experts and 30 interviewees participated in this study.The median age of the experts and interviewees were 48.0 and 38.5 years,respectively;51.66%and 54.8%of experts and interviewees,respectively,were men.The descriptors of facial diagrams of“people with the five elements in TCM”were complexion,shape,distribution state of facial bones,convergence trend of facial muscles,and facial expression.A theoretical model of“people with the five elements in TCM”was shaped based on these findings.Conclusion The study suggests a possibility for bridging the gap between personality and bodily state,identifying an avenue for personality research from the perspective of TCM.

Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen.Tirofiban,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic stroke.However,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear.Aim To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination.Methods Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in China.Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90.The primary endpoint is a new stroke or END within 90 days.The primary safety endpoint is severe or moderate bleeding within 90 days.Discussion The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI.Trial registration number NCT05310968.

HFD-exacerbated Metabolic Side Effects of Olanzapine Are Suppressed by ER Stress Inhibitor

Objective Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits.This study investigated the progressive deterioration of olanzapine-induced metabolic disorders in the presence of a high-fat diet(HFD)and explored the involvement of endoplasmic reticulum(ER)stress.Methods Female Sprague-Dawley rats fed on a standard chow diet or HFD were treated with olanzapine(3 mg/kg/day)and the ER stress inhibitor 4-phenylbutyric acid(4-PBA,1 and 0.5 g/kg/day)for 8 days.Changes in body weight,food intake,and plasma lipids were assessed.Hepatic fat accumulation was evaluated using oil red O staining.Western blotting and immunofluorescence assays were employed to examine the expression of ER stress markers,NOD-like receptor pyrin domain-containing protein 3(NLRP3),and proopiomelanocortin(POMC)in the hypothalamus or liver.Results Compared to olanzapine alone,olanzapine+HFD induced greater weight gain,increased hyperlipidemia,and enhanced hepatic fat accumulation(P<0.05).Co-treatment with 4-PBA exhibited a dose-dependent inhibition of these effects(P<0.05).Further mechanistic investigations revealed that olanzapine alone activated ER stress,upregulated NLRP3 expression in the hypothalamus and liver,and downregulated hypothalamic POMC expression.The HFD exacerbated these effects by 50%–100%.Moreover,co-administration of 4-PBA dose-dependently attenuated the olanzapine+HFD-induced alterations in ER stress,NLRP3,and POMC expression in the hypothalamus and liver(P<0.05).Conclusion HFD worsened olanzapine-induced weight gain and lipid metabolic disorders,possibly through ER stress-POMC and ER stress-NLRP3 signaling.ER stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders.

The Electrophysiology of Semantic Processing in Individuals with Autism Spectrum Disorder:A Meta-Analysis

Language difficulties vary widely among people with autism spectrum disorder(ASD).However,the semantic processing of autistic person and its underlying electrophysiological mechanism are still unclear.This meta-analysis aimed to explore the disturbance of semantic processing in patients with ASD.PubMed,Web of Science,and Embase were searched for eventrelated potential(ERP)studies on semantic processing in autistic people published in English before September 01,2022.Pooled estimates were calculated by fixed-effects or random-effects models according to the heterogeneity using Comprehensive Meta-Analysis 2.0.The potential moderators were explored by meta-regression and subgroup analysis.This meta-analysis has been registered at the Prospero International Prospective Register of Systematic Reviews(no.CRD 42021265852).A total of 14 articles and 18 studies,including 254 autistic people and 262 neurodevelopmental people were included in this meta-analysis.Compared to the comparison group,autistic people showed an overall reduced N400 amplitude(Hedges’g=0.350,p<0.001)in response to linguistic stimuli instead of non-linguistic stimuli.The N400 amplitude was affected by verbal intelligence and gender.The reduced overall N400 amplitude in autistic people under linguistic stimuli suggests a linguistic-specific deficit in semantic processing in individuals of autism.The decrease of N400 amplitude might be a promising indication of the pool language capacity of autism.

Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS): protocol of a prospective, multicentre, randomised, controlled trial

Background The superiority of balloon angioplasty plus aggressive medical management(AMM)to AMM alone for symptomatic intracranial artery stenosis(sICAS)on efficacy and safety profiles still lacks evidence from randomised controlled trials(RCTs).Aim To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS.Design Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis(BASIS)trial is a multicentre,prospective,randomised,open-label,blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS.Patients eligible in BASIS were 35–80 years old,with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis(70%–99%)of a major intracranial artery.The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio.Both groups will receive identical AMM,including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy,intensive risk factor management and life-style modification.All participants will be followed up for 3years.Study outcomes Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up,or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment,is the primary outcome.Discussion BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients,which may provide an alternative perspective for treating sICAS.Trial registration number NCT03703635;https://www.clinicaltrials.gov.

DNA methylation clocks for estimating biological age in Chinese cohorts

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG sites.However,a systematic comparison between DNA methylation data and other omics datasets has not yet been performed.Moreover,available DNAm age predictors are based on datasets with limited ethnic representation.To address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm changes.Additionally,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological age.The clocks were further employed to predict factors influencing aging rates.The DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age assessment.Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.

The differential effects of integrase strand transfer inhibitors and efavirenz on neuropsychiatric conditions and brain imaging in HIV-positive men who have sex with men

Integrase strand transfer inhibitors(INSTIs)have emerged as the first‐line choice for treating human immunodeficiency virus(HIV)infection due to their superior efficacy and safety.However,the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV(PLWH)is not fully understood due to limited data.In this study,we conducted a cross‐sectional examination of PLWH receiving antiretroviral therapy,with a specific focus on HIV‐positive men who have sex with men(MSM)on INSTI‐based regimens(n=61)and efavirenz(EFV)‐based regimens(n=28).Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging(MRI)scans,including T1‐weighted images and resting‐state functional MRI.Compared to the EFV group,the INSTI group exhibited primarily reduced gray matter volume(GMV)in the right superior parietal gyrus,higher regional homogeneity(ReHo)in the left postcentral gyrus,lower ReHo in the right orbital part of the inferior frontal gyrus,and increased voxel‐wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus.Furthermore,the analysis revealed a main effect of antiretroviral drugs on GMV changes,but no main effect of neuropsychiatric disorders or their interaction.The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group,validating the initial findings.Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI‐based regimens compared to those on EFV‐based regimens.These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI‐based regimens。

MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer

Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ aging.Here,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell senescence.To answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell models.We found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence phenotypes.We uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence phenotypes.Taken together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological conditions.However,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive.Here,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response mechanisms.Through comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular regeneration.We found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic processes.Altogether,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling

The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underlying human synovial aging remains poorly characterized.Here,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged individuals.By delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged MSCs.Moreover,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue fibrosis.In particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged synovium.In human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged donors.These data indicate an important role of FOXO1 in the regulation of human synovial aging.Overall,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.

Degeneration Directory:a multi-omics web resource for degenerative diseases

Background of database.Organ degeneration refers to the gradual decline in organ function and structure deterioration that occurs during aging,which represents the greatest risk factor for various degenerative diseases,including cardiovascular diseases,neurodegenerative diseases,and osteoarthritis,etc.(Aging Biomarker et al.,2023;Becker et al.,2018;Cai et al.,2022).

EEG Source Localization Using Spatio-Temporal Neural Network

Source localization of focal electrical activity from scalp electroencephalogram (sEEG) signal is generally modeled as an inverse problem that is highly ill-posed. In this paper, a novel source localization method is proposed to model the EEG inverse problem using spatio-temporal long-short term memory recurrent neural networks (LSTM). The network model consists of two parts, sEEG encoding and source decoding, to model the sEEG signal and receive the regression of source location. As there does not exist enough annotated sEEG signals correspond to specific source locations, simulated data is generated with forward model using finite element method (FEM) to act as a part of training signals. A framework for source localization is proposed to estimate the source position based on simulated training data. Experiments are done on simulated testing data. The results on simulated data exhibit good robustness on noise signal, and the proposed network solves the EEG inverse problem with spatio-temporal deep network. The result show that the proposed method overcomes the highly ill-posed linear inverse problem with data driven learning.

Effectiveness of cognitive behavioral therapy-based interventions on health outcomes in patients with coronary heart disease:A metaanalysis

BACKGROUND Recently,the efficacy of cognitive behavioral therapy(CBT)-based intervention on health outcomes in patients with coronary heart disease(CHD)has been recognized in randomized controlled trials(RCTs),but no comprehensive systematic review has been conducted.To address this research gap,our study aimed to evaluate whether comprehensive CBT-based interventions positively affect health outcomes in CHD patients.It was hypothesized that CBT-based interventions are effective in:(1)Reducing depression,anxiety,and stress symptoms;(2)Reducing body mass index,blood pressure,and lipid levels;and(3)Improving quality of life,and exercise endurance.AIM To verify the effectiveness of CBT-based interventions on CHD patients through a meta-analysis of previous publications.METHODS Relevant RCTs published in English were obtained by searching electronic databases,including PubMed,Embase,Cochrane Central Register of Controlled Trials,Scopus,and Proquest,with the retrieval time from inception to August 2020.The primary outcomes were psychological factors(depression,anxiety,and stress symptoms),physiological factors(body mass index,blood pressure,blood lipids).The secondary outcomes included quality of life and exercise endurance.We used Review Manager 5.3 to conduct the meta-analysis and used the Physiotherapy Evidence Database tool to evaluate the quality of studies.RESULTS A total of 22 RCTs comprising 4991 patients with CHD were included in the systematic review and meta-analysis.The main analysis revealed that CBT-based intervention can reduce depression symptoms:-2.00[95%confidence interval(CI):-2.83 to-1.16,P<0.001];anxiety symptoms:-2.07(95%CI:-3.39 to-0.75,P=0.002);stress symptoms:-3.33(95%CI:-4.23 to-2.44,P<0.001);body mass index:-0.47(95%CI:-0.81 to-0.13,P=0.006);and improve physical functioning:3.36(95%CI:1.63 to 5.10,P=0.000)and mental functioning:6.91(95%CI:4.10 to 9.73,P<0.001).Moreover,subgroup analysis results showed that CBT-based interventions were more effective for symptoms of depression and anxiety in CHD patients when individual,as opposed to group treatment,and psycho-education,behavioral and cognitive strategies were applied as the core treatment approaches.CONCLUSION CBT-based interventions are effective treatment strategies for CHD patients,significantly improving their symptoms of depression,anxiety and stress,body mass index,and health-related quality of life.