Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

Hippocampal dopamine as a key regulator for learning deficits in Parkinson's disease

Parkinson's disease(PD)is a progressive neurodegenerative disorder with clinical symptoms of involuntary or uncontrollable movements such as tremors,rigidity,and incoordination.The learning deficit is largely overlooked in the past because it is generally less impaired in the early stages of PD than in Alzheimer's disease.

Interoception mediates the association between social support and sociability in patients with major depressive disorder

BACKGROUND Interoception dysfunction has an important impact on the onset and development of major depressive disorder(MDD).Social support serves as a protective factor against MDD,and sociability also plays a significant role in this condition.These interconnected constructs-social support and sociability-play pivotal roles in MDD.However,no research on the mechanisms underlying the associations be-tween social support and sociability,particularly the potential role of interocep-tion,have been reported.ception,social support,and sociability,respectively.A mediation analysis model for the eight dimensions of intero-ception(noticing,not distracting,not worrying,attention regulation,emotional awareness,self-regulation,body listening,and trust),social support,and sociability were established to evaluate the mediating effects.RESULTS A partial correlation analysis of eight dimensions of the MAIA-2,SSRS,and TSBI scores,with demographic data as control variables,revealed pairwise correlations between the SSRS score and both the MAIA-2 score and TSBI score.In the major depression(MD)group,the SSRS score had a positive direct effect on the TSBI score,while the scores for body listening,emotional awareness,self-regulation,and trust in the MAIA-2C had indirect effects on the TSBI score.In the HC group,the SSRS score had a positive direct effect on the TSBI score,and the scores for attention regulation,emotional awareness,self-regulation,and trust in the MAIA-2C had indirect effects on the TSBI score.The proportion of mediators in the MD group was lower than that in the HC group.CONCLUSION Interoceptive awareness is a mediating factor in the association between social support and sociability in both HCs and depressed patients.Training in interoceptive awareness might not only help improve emotional regulation in depressed patients but also enhance their social skills and support networks.

Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder:A meta-analysis

BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.

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.

Relationship between left-behind status and cognitive function in older Chinese adults: a prospective 3-year cohort study

Background Due to the inaccuracy of the traditional geographical distance-based definition of left-behind status,data on the negative effect of left-behind status on cognitive function among older adults are controversial.Aims This study examined the cross-sectional and longitudinal associations of left-behind status with cognitive function in older Chinese adults.The left-behind status definition was based on the frequency of face-to-face parent-child meetings.Methods Data from a nationally representative sample of 8682 older adults(60+years)in 2015(5658 left behind and 3024 non-left behind),of which 6933 completed the follow-up in 2018,were obtained from the China Health and Retirement Longitudinal Study.Left-behind older adults werebroadlydefined as those aged 60+years who had living adult children and saw their children less than once per month.The cognitive function was assessed with a composite cognitive test with higher total scores indicating better cognitive function.Results Left-behind older adults had significantly lower cognitive test scores than non-left-behind older adults in both 2015(11.1(6.0)vs 13.2(5.9),t=15.863,p<0.001)and 2018(10.0(6.6)vs 12.4(6.7),t=14.177,p<0.001).After adjusting for demographic factors,lifestyle factors,chronic medical conditions and the baseline cognitive test score(in the longitudinal analysis only),on average,the cognitive test score of left-behind older adults was 0.628 lower than their non-left-behind counterparts in 2015(t=5.689,p<0.001).This difference in cognitive test scores attenuated to 0.322 but remained significant in 2018(t=2.733,p=0.006).Conclusions Left-behind older Chinese adults have a higher risk of poor cognitive function and cognitive decline than their non-left-behind counterparts.Specific efforts targeting left-behind older adults,such as encouraging adult children to visit their parents more regularly,are warranted to maintain or delay the progression of cognitive decline.

Research progress on the biological effects of BDNF and proBDNFs in post-traumatic stress disorder

Many people were affected psycho-logically and even traumatized by the outbreak of new coronavirus pneumonia in 2020,which has the potential to lead to post-traumatic stress disorder.Many neuropsy-chiatric illnesses are aided by brain-derived neurotrophic factor and its predecessors.Brain-derived neurotrophic factor precursors have the biological impact of triggering neuronal apoptosis and hindering neural regeneration,and brain-derived neurotrophic factor itself can help increase the growth,survival,and differentiation of central and peripheral nerve cells.This article provides an in-depth study of their biological impacts in post-traumatic stress disorder in an attempt to understand the biological effects of brain-derived neurotrophic factor and its precursor proteins.

Achyranthes bidentata polypeptides prevent apoptosis by inhibiting the glutamate current in cultured hippocampal neurons

Glutamate-induced excitotoxicity plays a critical role in the neurological impairment caused by middle cerebral artery occlusion.Achyranthes bidentata polypeptides have been shown to protect against neurological functional damage caused by middle cerebral artery occlusion,but the underlying neuroprotective mechanisms and the relationship to glutamate-induced excitotoxicity remain unclear.Therefore,in the current study,we investigated the protective effects of Achyranthes bidentata polypeptides against glutamate-induced excitotoxicity in cultured hippocampal neurons.Hippocampal neurons were treated with Mg^2+-free extracellular solution containing glutamate(300μM)for 3 hours as a model of glutamate-mediated excitotoxicity(glutamate group).In the normal group,hippocampal neurons were incubated in Mg^2+-free extracellular solution.In the Achyranthes bidentata polypeptide group,hippocampal neurons were incubated in Mg^2+-free extracellular solution containing glutamate(300μM)and Achyranthes bidentata polypeptide at different concentrations.At 24 hours after exposure to the agents,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Hoechst 33258 staining were used to assess neuronal viability and nuclear m'orphology,respectively.Caspase-3 expression and activity were evaluated using western blot assay and colorimetric enzymatic assay,respectively.At various time points after glutamate treatment,reactive oxygen species in cells were detected by H2 DCF-DA,and mitochondrial membrane potential was detected by rhodamine 123 staining.To examine the effect of Achyranthes bidentata polypeptides on glutamate receptors,electrophysiological recording was used to measure the glutamate-induced inward current in cultured hippocampal neurons.Achyranthes bidentata polypeptide decreased the percentage of apoptotic cells and reduced the changes in caspase-3 expression and activity induced by glutamate.In addition,Achyranthes bidentata polypeptide attenuated the amplitude of the glutamate-induced current.Furthermore,the glutamate-induced increase in intracellular reactive oxygen species and reduction in mitochondrial membrane potential were attenuated by Achyranthes bidentata polypeptide treatment.These findings collectively suggest that Achyranthes bidentata polypeptides exert a neuroprotective effect in cultured hippocampal neurons by suppressing the overactivation of glutamate receptors and inhibiting the caspase-3-dependent mitochondrial apoptotic pathway.All animal studies were approved by the Animal Care and Use Committee,Nantong University,China(approval No.20120216-001)on February 16,2012.

Association of the HTR2C-759CT polymorphism and antipsychotic-induced weight gain:a meta-analysis

Background Antipsychotic-induced weight gain(AIWG)is a crucial factor for the medication cessation of patients with schizophrenia.Multiple studies have shown that the functional polymorphism-759 C/T(rs3813929)in the HTR2C promoter region could possibly be correlated with AIWG.Aim To evaluate the genetic association of the HTR2C-759C/T polymorphism and AIWG in patients with schizophrenia with antipsychotic drugs(APDs)administration.Methods Eligible studies were identified by searching the following databases:PubMed,Embase,Web of Science,China Nation Knowledge Infrastructure(CNKI),VIP,Wanfang Data,Chinese Biomedical Literature Database(CBM)and the Airiti Library.The quality of studies was evaluated based on the Newcastle-Ottawa Scale.The pooled OR and 95%Cl were calculated for the dominant(CT/TT/T vs CC/C)mode,and subgroup analyses were performed based on ethnicity,antipsychotic medication and gender;ail statistical analyses were performed using the statistical software STATA V.12.0.Result A total of 17 studies with 3170 patients with schizophrenia were included in our meta-analysis.The result of the meta-analysis has shown that the association between the-759 C/T polymorphism and AIWG is statistically significant(OR 0.34,95%Cl:0.20 to 0.57,z=4.11,p<0.001).The subgroup analyses revealed significant correlations between the-759 C/T polymorphism and AIWG in the Caucasian population(OR 0.33,95%CI:0.14 to 0.77,z=2.55,p=0.011),the Asian population(OR 0.31,95%Cl:0.18 to 0.52,z=4.46,p<0.001),the patients with APDs administration(CT/JTfJ vs CC/C:OR 0.63,95%Cl:0.40 to 1.00,z=1.97,p=0.049)and the patients with atypical antipsychotic drug administration(CT/TT/T vs CC/C:OR 0.21,95%Cl:0.09 to 0.47,z=3.83,p<0.001).The sensitivity analysis showed that the results were stable.Begg's test(after correction z=1.07,p=0.287)and Egger's test(t=-2.41,p=0.029)show that the included articles have no significant publication bias.Conclusion There is a significant genetic association between HTR2C-759C/T and AIWG,and patients with T allele are less likely to have AIWG.

SHEsisEpi, a GPU-enhanced genome-wide SNP-SNP interaction scanning algorithm, efficiently reveals the risk genetic epistasis in bipolar disorder

Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium＇s （WTCCC） GWAS data of bipolar disorder （BPD） with 500K SNPs.

中国接受治疗的海洛因依赖患者中反社会人格障碍患病率的荟萃分析(英文)

背景：西方国家的研究持续报道海洛因成瘾者共患反社会人格障碍（Anitsocial Personality Disorder，ASPD）的比率很高，但中国海洛因成瘾者共患ASPD的报道比率变异很大，可能是因为中国的临床医生在治疗物质滥用问题时没有考虑人格问题。这份报告对评估中国海洛因依赖患者共患ASPD比率的研究做了系统分析。方法：我们检索了中国数据库（中国知网，万方数据知识服务平台，台湾电子期刊服务网）和西方数据库（PubMed和EMBASE）的相关研究。两位作者独立检索文献，确定符合预定纳入和排除标准的文献，评价纳入研究的文献质量，并提取用于分析的数据。使用StatsDirect 3.0进行统计分析。 结果：检索到15项符合条件的研究，共有3692例海洛因依赖患者。其中仅有2项高质量研究。所有的研究都是在康复中心或医院进行的。在这些患者中合并ASPD终生患病率为30％（95％CI：23~38％），但这些研究结果的异质性很大（I2=95％，p＆lt;0.001）。 男性患者的患病率显著高于女性（44％比21％），注射吸毒患者的患病率显著高于烫吸的患者（44％比27％）。研究方法较严谨的报道的海洛因依赖者ASPD患病率较高。 结论：虽然现有的有关中国接受治疗的海洛因依赖患者共患ASPD的文献存在较大的方法学问题，但据我们的分析，估计这些患者中大约有三分之一的人是符合ASPD诊断标准的。进一步需要开展的工作是提高临床医生对这一问题的认识，比较伴ASPD患者与不伴ASPD患者的发病机制、治疗效果和复吸情况，制定出适合这个治疗相对困难的海洛因依赖患者亚群的针对性的干预措施并加以验证。

Identification and predictive analysis for participants at ultra-high risk of psychosis:A comparison of three psychometric diagnostic interviews

BACKGROUND An accurate identification of individuals at ultra-high risk(UHR)based on psychometric tools to prospectively identify psychosis as early as possible is required for indicated preventive intervention.The diagnostic comparability of several psychometric tools,including the comprehensive assessment of at risk mental state(CAARMS),the structured interview for psychosis-risk syndrome(SIPS)and the bonn scale for the assessment of basic symptoms(BSABS),is unknown.AIM To address the psychometric comparability of CAARMS,SIPS and BSABS for subjects who are close relatives of patients with schizophrenia.METHODS In total,189 participants aged 18-58 years who were lineal relative by blood and collateral relatives by blood up to the third degree of kinship of patients with schizophrenia were interviewed in the period of May 2017 to January 2019.Relatives of the participants diagnosed schizophrenia were excluded.All the participants were assessed for a UHR state by three psychometric tools(CAARMS,SIPS and BSABS).The psychometric diagnosis results included at risk of psychosis(UHR+),not at risk of psychosis(UHR-)and psychosis.Demographic and clinical characteristics were also measured.The inter-rater agreement was assessed for evaluation of the coherence of the three scales.Transition rates for UHR+subjects to psychosis within 2 years were also recorded.RESULTS The overall agreement percentages were 93.12%,92.06%and 93.65%of CAARMS and SIPS,SIPS and BSABS and CAARMS and BSABS,respectively.The overall agreement percentage of the relative functional impairment of the three groups(UHR+,not at risk of psychosis and psychosis)were 89.24%,86.36%and 88.12%,respectively.The inter-rater reliability of the CAARMS,SIPS and BSABS total score was 0.90,0.89 and 0.85.The inter-rater reliability was very good to excellent for all the subscales of these three instruments.For CAARMS,SIPS and BSABS,the kappa coefficient about UHR criteria agreement was 0.87,0.84 and 0.82,respectively(P<0.001).The transition rates of UHR+to psychosis within 2 years were 16.7%(CAARMS),10.0%(SIPS)and 17.7%(BSABS).CONCLUSION There is good diagnostic agreement between the CAARMS,SIPS and BSABS towards identification of UHR participants who are close relatives of patients with schizophrenia.

Protective Effect of Salidroside on Mitochondrial Disturbances via Reducing Mitophagy and Preserving Mitochondrial Morphology in OGD-induced Neuronal Injury

Salidroside is the active ingredient extracted from Rhodiola rosea,and has been reported to show protective effects in cerebral ischemia,but the exact mechanisms of neuronal protective effects are still unrevealed.In this study,the protective effects of salidroside(1 jimol/L)in ameliorating neuronal injuries induced by oxygen-glucose deprivation(OGD),which is a classical model of cerebral ischemia,were clarified.The results showed that after 8 h of OGD,the mouse hippocampal neuronal cell line HT22 cells showed increased cell death,accompanied with mitochondrial fragmentation and augmented mitophagy.However,the cell viability of HT22 cells showed significant restoration after salidroside treatment.Mitochondrial morphology and mitochondrial function were effectively preserved by salidroside treatment.The protective effects of salidroside were further related to the prevention of mitochondrial over-fission.The results showed that mTOR could be recruited to the mitochondria after salidroside treatment,which might be responsible for inhibiting excessive mitophagy caused by OGD.Thus,salidroside was shown to play a protective role in reducing neuronal death under OGD by safeguarding mitochondrial function,which may provide evidence for further translational studies of salidroside in ischemic diseases.

Identification of a functional 339 bp Alu insertion polymorphism in the schizophrenia-associated locus at 10q24.32

Genome-wide association studies(GWAS)have identified multiple single nucleotide polymorphisms(SNPs)or small indels robustly associated with schizophrenia;however,the functional risk variations remain largely unknown.We investigated the 10q24.32 locus and discovered a 339 bp Alu insertion polymorphism(rs71389983)in complete linkage disequilibrium(LD)with the schizophrenia GWAS risk variant rs7914558.The presence of the Alu insertion at rs71389983 strongly repressed transcriptional activities in in vitro luciferase assays.This polymorphism may be a target for future mechanistic research.Our study also underlines the importance and necessity of considering previously underestimated Alu polymorphisms in future genetic studies of schizophrenia.

How psychiatrists coordinate treatment for COVID-19: a retrospective study and experience from China

Background Patients with C0VID-19 are at high risk of developing mental health problems;however,the prevalence and management of mental disorders and how psychiatrists coordinate the treatment are unclear.Aims We aimed to investigate the mental health problems of patients infected with C0VID-19 and to identify the role of psychiatrists in the clinical treatment team during the pandemic.We also share the experience of psychiatric consultations of patients with COVID-19 in Shanghai,China.Methods We analysed data from the psychiatric medical records of 329 patients with COVID-19 in the Shanghai Public Health Clinical Center from 20 January to 8 March 2020.We collected information including sociodemographic characteristics,whether patients received psychiatric consultation,mental health symptoms,psychiatric diagnoses,psychiatric treatments and severity level of COVID-19.Results Psychiatric consultations were received by 84(25.5%)patients with COVID-19.The most common symptoms of mental health problems were sleep disorders(75%),anxiety(58.3%)and depressive symptoms(11.9%).The psychiatric consultation rate was highest in critically ill patients(69.2%),with affective symptoms or disturbed behaviour as their main mental health problems.Psychiatric diagnoses for patients who received consultation included acute stress reaction(39.3%),sleep disorders(33.3%),anxiety(15.5%),depression(7.1%)and delirium(4.8%).In terms of psychiatric treatments,86.9%of patients who received psychiatric consultation were treated with psychotropic medications,including non-benzodiazepine sedative-hypnotic agents(54.8%),antidepressants(26.2%),benzodiazepines(22.6%)and antipsychotics(10.7%).Among the 76 patients who were discharged from the hospital,79%had recovered from mental health problems and were not prescribed any psychotropic medications.The symptoms of the remaining 21%of patients had improved and they were prescribed medications to continue the treatment.Conclusions This is the first study to report psychiatric consultations for patients with COVID-19.Our study indicated that a considerable proportion of patients with COVID-19,especially critically ill cases,experienced mental health problems.Given the remarkable effect of psychiatric treatments,we recommend that psychiatrists be timely and actively involved in the treatment of COVID-19.

Clinical characteristics of hospitalised patients with schizophrenia who were suspected to have coronavirus disease(COVID-19)in Hubei Province,China

Background Since the outbreak of C0VID-19,no data have been available for hospitalised psychiatric patients who are suspected to have COVID-19.We performed a comprehensive investigation of the clinical features of hospitalised patients with schizophrenia with or without suspected COVID-19 in Hubei Province,China.Aim To explore the clinical characteristics of hospitalised patients with schizophrenia with suspected COVID-19 in Hubei Province,China.M ethods 21 hospitalised patients with schizophrenia with suspected COVID-19(COVID-19 suspected group)in the isolation ward of a mental health hospital in Wuhan and 30 hospitalised patients with schizophrenia(clean group)in the general ward of another mental health hospital in Yichang were recruited.We retrospectively reviewed their clinical characteristics,laboratory findings and chest CT results before 21 February 2020.We also compared the emotional and mental symptoms between the two groups.Results Medical records revealed that 21 COVID-19 suspected patients were transferred to the isolation ward between 30 January 2020 and 15 February 2020.The mean age(SD)of COVID-19 suspected patients was 43.1(2.6).12(57.1%)patients showed abnormalities on chest CT before onset of respiratory symptoms.14(66.7%)patients had psychiatric medications adjustment after detection of abnormal chest CT findings.By 21 February,one patient was confirmed to have COVID-19.Even though the remaining 20(95.2%)were negative for at least two reverse transcription PCR tests,11(52.4%)patients met the diagnostic criteria for clinically confirmed cases.Compared with patients in the clean group,patients in the suspected COVID-19 group showed significantly higher stress,depression and anxiety levels and poorer sleep quality.Conclusion Setting up an independent isolation ward for hospitalised psychiatric patients who are suspected to have symptoms of COVID-19 helped control the spread of the epidemic.Patients with schizophrenia suspected to have COVID-19 showed increased stress and mood and sleep disturbances,which should be appropriately managed.

电针改善躯体形式障碍患者睡眠脑电及事件相关电位的临床研究

目的:观察电针治疗对躯体形式障碍(SFD)患者睡眠脑电及事件相关电位(ERP)的影响。方法:选择75例SFD患者为电针组,予以电针神庭和百会治疗,每次30 min,每日1次,连续治疗6 d为1个疗程,疗程间休息1 d,共治疗4个疗程。治疗前采用躯体症状检查报告单对患者的主要症状进行调查。治疗前和治疗后进行睡眠脑电Quisi监测,检测ERP失匹配负波(MMN)和P300。对40名正常人进行相同的睡眠脑电Quisi监测和ERP检测,作为正常对照组数据。结果:研究过程中电针组13例患者因资料不全被剔除,最终有62例纳入统计分析。在62例SFD患者中,困扰患者的主要症状依次是认知功能障碍、睡眠障碍、呼吸系统、消化系统、五官及心血管系统症状。与正常对照组比较,治疗前电针组患者ERP的MMN及P300潜伏期延长,波幅下降,组间差异均有统计学差异(P<0.01或P<0.05);Quisi指标中睡眠总时间(TST)减少;快速动眼睡眠(REM)潜伏期(RL)缩短,REM时间(RT)减少,REM周期数(NRP)减少;睡眠潜伏期(SL)延长,醒觉时间(AT)增加,睡眠效率(SE)下降;非快速动眼睡眠(NREM)第一阶段(S1)占比增加,第二阶段(S2)占比降低,慢波睡眠(SWS),即NREM第三阶段和第四阶段(S3+S4)占比降低,组间差异均有统计学意义(P<0.01或P<0.05)。治疗4个疗程后,电针组患者ERP的MMN和P300潜伏期缩短,波幅增大,与本组治疗前均有统计学差异(P<0.05),与正常对照组差异均无统计学意义(P>0.05);Quisi指标中电针组的TST增加,RL延长,SL缩短,AT减少;睡眠结构的主要改变是S1占比减少,S2占比增加,SE提高,与本组治疗前差异均有统计学意义(P<0.01或P<0.05);NRP的组内差异无统计学意义(P>0.05)。除TST、RT、S1占比及SWS外,其他Quisi指标(包括RL、NRP、SL、AT、SE及S2占比)的组间差异均无统计学意义(P>0.05)。结论:SFD患者的临床症状表现多样,多数患者存在睡眠脑电及ERP异常;电针治疗可纠正SFD患者异常的睡眠脑电指标及ERP的MMN和P300。

Morphological Tracing and Functional Identification of Monosynaptic Connections in the Brain:A Comprehensive Guide

Behavioral studies play a crucial role in unraveling the mechanisms underlying brain function.Recent advances in optogenetics,neuronal typing and labeling,and circuit tracing have facilitated the dissection of the neural circuitry involved in various important behaviors.The identification of monosynaptic connections,both upstream and downstream of specific neurons,serves as the foundation for understanding complex neural circuits and studying behavioral mechanisms.However,the practical implementation and mechanistic understanding of monosynaptic connection tracing techniques and functional identification remain challenging,particularly for inexperienced researchers.Improper application of these methods and misinterpretation of results can impede experimental progress and lead to erroneous conclusions.In this paper,we present a comprehensive description of the principles,specific operational details,and key steps involved in tracing anterograde and retrograde monosynaptic connections.We outline the process of functionally identifying monosynaptic connections through the integration of optogenetics and electrophysiological techniques,providing practical guidance for researchers.

Microglia Suppresses Breast Cancer Brain Metastasis via a Pro-inflammatory Response

Due to the obstacle of the blood-brain barrier(BBB)for drug delivery[1],breast cancer brain metastasis(BCBM)represents a worldwide health challenge with high mortality.During BCBM formation and progression,brain metastases(BrMs)secret various factors,including cytokines and exosomes,and trigger the infiltration of tumours-associated macrophages(TAMs),which in turn become important components of brain tumour microenvironments(TME).

Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium

Ion channel activation upon ligand gating triggers a myriad of biological events and,therefore,evolution of ligand gating mechanism is of fundamental importance.TRPM2,a typical ancient ion channel,is activated by adenosine diphosphate ribose(ADPR)and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates,but the evolutionary process is still unknown.Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that,the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation,while the N-terminal MHR domain maintains a conserved ligand binding site.Calcium gating pattern has also evolved,from one Ca^(2+)-binding site as in sea anemones to three sites as in human.Importantly,we identified a new group represented by olTRPM2,which has a novel gating mode and fills the missing link of the channel gating evolution.We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated.Such findings benefit the evolutionary investigations of other channels and proteins.