Assessing the effectiveness of internetbased interventions for mental health outcomes:an umbrella review

Internet-based interventions(IBIs)for behavioural health have been prevalent for over two decades,and a growing proportion of individuals with mental health concerns prefer these emerging digital alternatives.However,the effectiveness and acceptability of IBIs for various mental health disorders continue to be subject to scholarly debate.We performed an umbrella review of meta-analyses(MAs),conducting literature searches in PubMed,Web of Science,Embase,Cochrane and Ovid Medline from their inception to 17 January 2023.A total of 87MAs,reporting on 1683 randomised controlled trials and 295589 patients,were included.The results indicated that IBIs had a moderate effect on anxiety disorder(standardised mean difference(SMD)=0.53,95%CI 0.44 to 0.62)and post-traumatic stress disorder(PTSD)(SMD=0.63,95%CI 0.38 to 0.89).In contrast,the efficacy on depression(SMD=0.45,95%CI 0.39 to 0.52),addiction(SMD=0.23,95%CI 0.16 to 0.31),suicidal ideation(SMD=0.23,95%CI 0.16 to 0.30),stress(SMD=0.41,95%CI 0.33 to 0.48)and obsessive-compulsive disorder(SMD=0.47,95%CI 0.22 to 0.73)was relatively small.However,no significant effects were observed for personality disorders(SMD=0.07,95%CI-0.13 to 0.26).Our findings suggest a significant association between IBIs and improved mental health outcomes,with particular effectiveness noted in treating anxiety disorders and PTSD.However,it is noteworthy that the effectiveness of IBIs was impacted by high dropout rates during treatment.Furthermore,our results indicated that guided IBIs proved to be more effective than unguided ones,playing a positive role in reducing dropout rates and enhancing patient adherence rates.

Scarcity and Mental Health—Multiple Mediators of Sleep Quality and Life Satisfaction

Background:In the current social environment,scarcity,as a universally present objective state,profoundly impacts individuals’decision-making and health through the subjective feeling it induces,known as a“scarcity mindset.”Particularly,the feeling of scarcity related to money and sleep time is not only widespread but also directly linked to an individual’s mental health.Purpose:This study aims to delve into the relationship between the feeling of scarcity and mental health,with a specific focus on the relationship between the feeling of money scarcity or sleep time scarcity and mental health,as well as the role of sleep quality or life satisfaction in this relationship.Procedure:We determined the sampling quotas based on the population and economic development levels of each province in the“China Statistical Yearbook(2021)”(National Bureau of Statistics,2021).Participants were selected using the Probability Proportional to Size(PPS)sampling method.Data was collected by distributing online questionnaires to participants,and the relationships between the main variables were explored using structural equation modeling.Results:1.In China,the feeling of sleep time scarcity is stronger than the feeling of money scarcity among the public.2.The feeling of money scarcity is positively correlated with depression and anxiety,whereas the feeling of sleep time scarcity is only positively correlated with depression.3.The feeling of scarcity mainly leads to depression and self-denial through reducing life satisfaction,and it leads to anxiety through reducing sleep quality.Conclusion:The feeling of scarcity in money and sleep time is related to different dimensions of mental health.Therefore,reasonably planning financial allocation and ensuring an adequate amount of sleep can reduce the sense of scarcity,thereby improving mental health.Additionally,improving sleep quality and increasing life satisfaction can alleviate the adverse effects of scarcity on mental health.

The Impact of Sleep Determination on Procrastination before Bedtime:The Role of Anxiety

Objective:The importance of good sleep for energy recovery and overall physical and mental health cannot be overstated.However,the increasing competitiveness of society,diversifying lifestyles,and the rapid spread of the internet and electronic devices have significantly impacted people’s sleep patterns,particularly through bedtime procrastination.Therefore,this study aims to investigate the relationship and underlying mechanisms between sleep determination,anxiety,and bedtime procrastination among the Chinese population.Method:The study utilized data from a national survey—the China Residents’Sleep Condition Survey(November 2021,with 6,037 participants).By constructing mediation and moderation models,it analyzed the relationship and mechanisms between sleep determination and bedtime procrastination,highlighting the dual role of anxiety:as a mediator between sleep determination and bedtime procrastination,and as a moderator of their relationship.Results:There was a negative correlation between sleep determination and bedtime procrastination;anxiety was related to an increase in bedtime procrastination behaviors;In the interplay between sleep determination and pre-bedtime procrastination,the regulatory effect of anxiety is found to be more pronounced than its intermediary role,with anxiety significantly diminishing the inverse relationship between sleep determination and procrastination before bedtime.Conclusion:Bedtime procrastination can lead to sleep issues,thus reducing sleep quality.Enhancing sleep determination or alleviating pre-sleep anxiety can help inhibit bedtime procrastination behaviors.Intervening and reducing bedtime procrastination is one of the effective measures to improve sleep quality.

Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease

Background Previous studies havedemonstrated that excitatory repetitive transcranial magnetic stimulation(rTMS)can improve the cognitive function of patients with Alzheimer's disease(AD).Intermittent theta burst stimulation(iTBS)is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD.However,the long-term effects of iTBS on cognitive decline and brain structure in patients with AD areunknown.Aims We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD.Methods In this randomised,assessor-blinded,controlled trial,iTBS was administered to the left dorsolateral prefrontal cortex(DLPFC)of 42 patients with AD for 14days every 13weeks.Measurements included the Montreal Cognitive Assessment(MoCA),a comprehensive neuropsychological battery,and the grey matter volume(GMV)of the hippocampus.Patients were evaluated at baseline and after follow-up.The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time.Results The iTBS group maintained MoCA scores relative to the control group(t=3.26,p=0.013)and reduced hippocampal atrophy,which was significantly correlated with global degeneration scale changes.The baseline Mini-Mental State Examination(MMSE)score,apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up.Moreover,the GMV of the left(t=0.08,p=0.996)and right(t=0.19,p=0.977)hippocampus were maintained in the active group but significantly declined in the control group(left:t=4.13,p<0.001;right:t=5.31,p<0.001).GMV change in the left(r=0.35,p=0.023)and right(r=0.36,p=0.021)hippocampus across the intervention positively correlated with MoCA changes;left hippocampal GMV change was negatively correlated with global degeneration scale(r=-0.32,p=0.041)changes.Conclusions DLPFC-iTBS maybe a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD,providing a new AD treatment option.Trial registration number NCT04754152.

Biological mechanisms and clinical efficacy of sulforaphane for mental disorders

Current clinical management of major mental disorders,such as autism spectrum disorder,depression and schizophrenia,is less than optimal.Recent scientific advances have indicated that deficits in oxidative and inflammation systems are lessthanoptimal.Recentscientific advances have indicated extensively involved in the pathogenesis of these disorders. These findings have led to expanded considerations for treatment.Sulforaphane(SFN)is a dietary phytochemical extracted from cruciferous vegetables.It is an effective activator of the transcription factor nuclear erythroid-2 like factor-2,which can upregulate multiple antioxidants and protect neurons against various oxidative damages.On the other hand,it can also significantly reduce inflammatory response to pathological states and decrease the damage caused by the immune response via the nuclear factor-kB pathway and other pathways.In this review,we introduce the biological mechanisms of SFN and the pilot evidence from its clinical trials of major mental disorders,hoping to promote an increase in psychiatric clinical studies of SFN.

Resting-state electroencephalography theta predicts neurofeedback treatment 4-month follow-up response in nicotine addiction

Background The high rate of long-term relapse is a major cause of smoking cessation failure.Recently,neurofeedback training has been widely used in the treatment of nicotine addiction;however,approximately 30%of subjects fail to benefit from this intervention.Our previous randomised clinical trial(RCT)examined cognition-guided neurofeedback and demonstrated a significant decrease in daily cigarette consumption at the 4-month follow-up.However,significant individual differences were observed in the 4-month follow-up effects of decreased cigarette consumption.Therefore,it is critical to identify who will benefit from pre-neurofeedback.Aims We examined whether the resting-state electroencephalography(EEG)characteristics from pre-neurofeedback predicted the 4-month follow-up effects and explored the possible mechanisms.Methods This was a double-blind RCT.A total of 60 participants with nicotine dependence were randomly assigned to either the real-feedback or yoked-feedback group.They underwent 6 min closed-eye resting EEG recordings both before and after two neurofeedback sessions.A follow-up assessment was conducted after 4 months.Results The frontal resting-state theta power spectral density(PSD)was significantly altered in the real-feedback group after two neurofeedback visits.Higher theta PSD in the real-feedback group before neurofeedback was the only predictor of decreased cigarette consumption at the 4-month follow-up.Further reliability analysis revealed a significant positive correlation between theta PSD pre-neurofeedback and post-neurofeedback.A leave-one-out cross-validated linear regression of the theta PSD pre-neurofeedback demonstrated a significant correlation between the predicted and observed reductions in cigarette consumption at the 4-month follow-up.Finally,source analysis revealed that the brain mechanisms of the theta PSD predictor were located in the orbital frontal cortex.Conclusions Our study demonstrated changes in the resting-state theta PSD following neurofeedback training.Moreover,the resting-state theta PSD may serve as a prognostic marker of neurofeedback effects.A higher resting-state theta PSD predicts a better long-term response to neurofeedback treatment,which may facilitate the selection of individualised interventions.

Empowerment according to Persons with Severe Mental Illness: Development of the Netherlands Empowerment List and Its Psychometric Properties

Objectives. It is unclear whether and to what extent purportedly empowering practices in mental health care, like rehabilitation programs, recovery-supporting mental health care environments and peer-run services, contribute to the process of empowerment. Several American empowerment questionnaires have been developed in recent years, facilitating the measurement of empowerment outcomes. Given likely major transatlantic cultural differences in a value-sensitive concept such as empowerment, this article describes the development of the Netherlands Empowerment List (NEL) and its psychometric properties. Methods. Patients in Dutch mental health services provided meaning to the empowerment concept from which the NEL was derived. Based on 531 completed questionnaires, analyses in agreement with COSMIN criteria examined aspects of internal consistency, content validity, structural validity, convergent validity, discriminant validity, reproducibility and responsiveness of the NEL. Results. The NEL is a 40-item self-report questionnaire with six subscales: Social support, Professional help, Connectedness, Confidence and purpose, Self-management and Caring community. Internal consistency (Cronbach’s alpha = 0.94), aspects of validity, reproducibility (intraclass correlation = 0.79) and responsiveness were good. Correlation with existing scales was the highest for the Mental Health Confidence Scale (r = 0.78) and the lowest for the Boston Empowerment Scale (r = 0.61). Conclusion. The NEL appears to be a suitable instrument to capture the dimension of empowerment in European mental health settings.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations

BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.

The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

Dissecting the association between gut microbiota,body mass index and specific depressive symptoms:a mediation Mendelian randomisation study

Background Observational studies highlight the association between gut microbiota(GM)composition and depression;however,evidence for the causal relationship between GM and specific depressive symptoms remains lacking.Aims We aimed to evaluate the causal relationship between GM and specific depressive symptoms as well as the mediating role of body mass index(BMI).Methods We performed a two-sample Mendelian randomisation(MR)analysis using genetic variants associated with GM and specific depressive symptoms from genome-wide association studies.The mediating role of BMI was subsequently explored using mediation analysis via two-step MR.Results MR evidence suggested the Bifidobacterium genus(β=0.03;95%CI-0.05 to-0.02;p<0.001 andβ=0.03;95%CI-0.05 to-0.02;p<0.001)and Actinobacteria phylum(β=-0.04;95%CI-0.06 to-0.02;p<0.001 andβ=-0.03;95%CI-0.05 to-0.03;p=0.001)had protective effects on both anhedonia and depressed mood.The Actinobacteria phylum also had protective effects on appetite changes(β=-0.04;95%CI-0.06 to-0.01;p=0.005),while the FamilyⅪhad an antiprotective effect(β=0.03;95%CI 0.01 to 0.04;p<0.001).The Bifidobacteriaceae family(β=-0.01;95%CI-0.02 to-0.01;p=0.001)and Actinobacteria phylum(β=-0.02;95%CI-0.03 to-0.01;p=0.001)showed protective effects against suicidality.The two-step MR analysis revealed that BMl also acted as a mediating moderator between the Actinobacteria phylum and appetite changes(mediated proportion,34.42%)and that BMI partially mediated the effect of the Bifidobacterium genus(14.14%and 8.05%)and Actinobacteria phylum(13.10%and 8.31%)on both anhedonia and depressed mood.Conclusions These findings suggest a potential therapeutic effect of Actinobacteria and Bifidobacterium on both depression and obesity.Further studies are required to translate these findings into clinical practice.

Human small intestine is capable of restoring barrier function after short ischemic periods

AIM To assess intestinal barrier function during human intestinal ischemia and reperfusion(IR).METHODS In a human experimental model,6 cm of jejunum was selectively exposed to 30 min of ischemia(I) followed by 30 and 120 min of reperfusion(R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose(L) and rhamnose(R). Plasma concentrations of citrulline,an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions( TJs),by plasma marker for enterocytes damage(I-FABP) and analyzed by electron microscopy(EM) using lanthanum nitrate as an electrondense marker.RESULTS Plasma L/R ratio's were significantly increased after 30 min of ischemia(30 I) followed by 30 min of reperfusion(30 R) compared to control(0.75 ± 0.10 vs 0.20 ± 0.09,P < 0.05). At 120 min of reperfusion(120 R),ratio's normalized(0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points(correlation: 0.467,P < 0.01). TJs staining shows distortion of staining at 30 I. An intact lining of TJs was again observed at 30 I120 R. Electron microscopy analysis revealed disrupted TJs after 30 I with paracellular leakage of lanthanum nitrate,which restored after 30 I120 R. Furthermore,citrulline concentrations closely paralleled the histological perturbations during intestinal IR.CONCLUSION This study directly correlates histological data with intestinal permeability tests,revealing that the human gut has the ability of to withstand short episodes of ischemia,with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.

Prediction of adolescent subjective well being: A machine learning approach

Background Subjective well-being(SWB),also known as happiness,plays an important role in evaluating both mental and physical health.Adolescents deserve specific attention because they are under a great variety of stresses and are at risk for mental disorders during adulthood.Aim The present paper aims to predict undergraduate students1 SWB by machine learning method.Methods Gradient Boosting Classifier which was an innovative yet validated machine learning approach was used to analyse data from 10518 Chinese adolescents.The online survey included 298 factors such as depression and personality.Quality control procedure was used to minimise biases due to online survey reports.We applied feature selection to achieve the balance between optimal prediction and result interpretation.Results The top 20 happiness risks and protective factors were finally brought into the predicting model.Approximately 90%individuals'SWB can be predicted correctly,and the sensitivity and specificity were about 92%and 90%,respectively.Conclusions This result identifies at-risk individuals according to new characteristics and established the foundation for adolescent prevention strategies.

Randomized trial estimating effects of hypnosis versus progressive muscle relaxation on medical students’test anxiety and attentional bias

BACKGROUND Test anxiety is prevalent among medical students and leads to impaired academic performance.Test-related attentional bias has been identified as an important maintaining factor in test-anxious individuals.AIM To evaluate whether hypnosis and progressive muscle relaxation(PMR)could modify medical college students’test anxiety and attentional bias.METHODS A total of 598 medical students were screened.The participants were divided into higher and lower test anxiety groups according to their scores on the test anxiety scale(TAS).Ninety medical college students with high TAS score were randomly assigned to a hypnosis or PMR group.Another 45 students with low TAS score were included,forming a baseline control group.The intervention was conducted weekly for 6 wk,and each session lasted approximately 30 min.The total intervention time and the number of intervention sessions for the hypnosis and PMR groups were equal.Data were collected at the pretest,posttest,and 2-mo follow-up.RESULTS Hypnosis group participants had a significantly lower TAS score at posttest(t=-21.827,P<0.001)and at follow-up(t=-14.824,P<0.001),compared to that at pretest.PMR group participants also had a significantly lower TAS score at posttest(t=-10.777,P<0.001)and at follow-up(t=-7.444,P<0.001),compared to that at pretest.At the posttest level,the hypnosis group had a significantly lower TAS score than the PMR group(t=-3.664,P<0.001).At the follow-up level,the hypnosis group also had a significantly lower TAS score than the PMR group(t=-2.943,P=0.004).Clinically significant improvement was found in both the hypnosis and PMR groups(hypnosis=64.0%;PMR=62.22%).Hypnosis was more effective than PMR in reducing test anxiety among medical college students.Hypnosis could modify attentional bias toward threatening stimuli,but PMR could not.CONCLUSION These results suggest that attentional bias plays an important role in test anxiety treatment.

Biomarkers for early diagnosis of autism obtained through bioinformatics analysis of human blood sample

Objective:autism spectrum disorder(ASD),a serious disorder that begins early in life,con-tinues throughout the lifespan.Children with ASD who are diagnosed early are more responsive to therapeutic interventions and have less social and language impair-ment than children diagnosed later;however,current di-agnostic measures are mostly applied to children older than one year and lack the appropriate biological markers for early diagnosis of ASD.Using bioinformatic analy-sis,this study explores the molecular information mech-anism of ASD.Method:in this study,we used dataset GSE6575 from Gene Expression Omnibus(GEO)to an-alyze the mRNA expression profile of ASD,including 35 ASD samples and 12 normal control samples looking for different genes and we did enrichment analysis of those genes.We then used the STRING database to construct a protein-protein interaction(PPI)network of differential genes.Finally,Cytoscape plug-in cytoHubba was used to search for hub genes.The diagnostic value of the hub genes was verified by subject operating characteristic curves.Result:we looked for 50 different genes and did an enrichment analysis of those genes.The results of the enrichment analysis showed that these differential genes were mainly concentrated in the response to viruses,the immune regulation of inflammation and energy metabo-lism.Using Cytoscape plug-in cytoHubba,we found ten different genes.We drew ROC curves for all ten genes among which two genes,interleukin 2 receptor subunit beta(IL2Rβ)and perforin 1(PRF1),had good sensitivity and specificity for the early diagnosis of autism.The ar-eas under the ROC curves were 0.855,0.830 for IL2Rβ,PRF1.Conclusion:data analysis using the GEO data-base can provide new insights into the etiology of ASD as well as some possible biomarkers and therapeutic targets for early diagnosis and treatment of ASD.

The Application of Extended Reality in Treating Children with Autism Spectrum Disorder

Autism Spectrum Disorder(ASD)is a common neurodevelopmental disorder in children,characterized by social interaction,communication difficulties,and repetitive and stereotyped behaviors.Existing intervention methods have limitations,such as requiring long treatment periods and needing to be more convenient to implement.Extended Reality(XR)technology offers a virtual environment to enhance children's social,communication,and self-regulation skills.This paper compares XR theoretical models,application examples,and intervention effects.The study reveals that XR intervention therapy is mainly based on cognitive rehabilitation,teaching,and social-emotional learning theories.It utilizes algorithms,models,artificial intelligence(AI),eye-tracking,and other technologies for interaction,achieving diverse intervention outcomes.Participants showed effective improvement in competency barriers using XR-based multimodal interactive platforms.However,Mixed Reality(MR)technology still requires further development.Future research should explore multimsodal interaction technologies combining XR and AI,optimize models,prioritize the development of MR intervention scenarios,and sustain an optimal intervention level.

miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied.MicroRNAs(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA translation.Here,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model cells.We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation.More importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

A novel neuroprotective method against ischemic stroke by accelerating the drainage of brain interstitial fluid

Ischemic stroke is a leading cause of death and disability worldwide.Inflammatory response after stroke determines the outcome of ischemic injury.A recent study has reported an efficient method,epidural arterial implantation(EAI),for accelerating interstitial fluid(ISF)drainage,which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space(ECS).In this study,the method of EAI was modified(m-EAI)to control its function of accelerating the ISF drainage at different time points following ischemic attack.The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion(tMCAO)rat model.The results demonstrated the accumulation of IL-1β,IL-6,and TNF-αwas significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats,accompanied with decreased infarct volume and improved neurological function.This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS.Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.

Circular RNAs in early brain development and their influence and clinical significance in neuropsychiatric disorders

Neuropsychiatric disorders represent a set of severe and complex mental illnesses,and the exact etiologies of which are unknown.It has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric disorders.Currently,the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment,because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental illness.Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA (ncRNA) with a closed-loop structure.In recent years,there have been tremendous advances in our understanding of the expression profiles and biological roles of circRNAs.In the brain,circRNAs are particularly enriched and are expressed more abundantly in contrast to linear counterpart transcripts.They are highly active at neuronal synapses.These features make circRNAs uniquely crucial for understanding brain health,disease,and neuropsychiatric disorders.This review focuses on the role of circRNAs in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric disorders.In addition,we discuss the potential for blood or cerebrospinal fluid circRNAs to be used as novel biomarkers in the early diagnosis of neuropsychiatric disorders.The findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders.

Nicotine dependence in community-dwelling Chinese patients with schizophrenia

Background Smoking is a serious public health problem. Patients with schizophrenia usually have a higher prevalence of smoking than the general population, but the level of nicotine dependence is seldom studied, especially for patients living in the communities. Aims This study aimed to examine the level of nicotine dependence in Chinese community-dwelling patients with schizophrenia and explored its associated sociodemographic and clinical factors. Methods A total of 621 patients with schizophrenia treated in the primary care centres of Guangzhou were consecutively recruited. The level of nicotine dependence was assessed with the Chinese version of the Fagerstrom Test for Nicotine Dependence (FTND). Results 148 patients with schizophrenia were current smokers, and the mean (SD) score of FTND was 5.06 (2.55) for all the current smokers. The prevalence of nicotine addiction was 48.0%(95% Cl: 40.0%-56.0%) in patients with current smoking. The patients with schizophrenia had a significantly higher level of nicotine dependence than the Chinese general population. Multiple linear regression analysis revealed that male gender, being unemployed, having a family history of psychiatric disorders, having major medical conditions, first illness episode and less severe positive symptoms were significantly associated with a higher level of nicotine dependence. Conclusion Community-dwelling patients with schizophrenia in China, especially male patients, had a higher level of nicotine dependence than the general population.

Will male semen quality improve with environmental quality?

Wenzhou has improved its environmental quality because of comprehensive environmental remediation;nevertheless,the semen quality of infertile males remains unclear.This study determined whether better environmental quality improved semen quality in this region.We recorded semen quality data from 22962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University(Wenzhou,China).Patients were predominantly 30–35 years old(33.1%)and workers(82.0%),with high school education or lower(77.6%);more than a half of the patients(52.6%)were Wenzhou household registration;and most patients(77.5%)had abnormal semen quality.Patients who were older than 40 years and workers,and those with Wenzhou household registration,had significantly worse semen quality(all P<0.05).From 2014 to 2019,progressive sperm motility,total sperm motility,and semen volume showed increasing linear trends in all patients(P=0.021,0.030,and 0.005,respectively),yet normal sperm morphology showed a linearly decreasing trend(P=0.046).Sensitivity analyses for subgroups yielded similar results.In conclusion,the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility,total sperm motility,and semen volume.Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.