Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise....Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise.In China,the average age of firsttime stroke patients is 66.4 years,and the intravenous thrombolysis rate using recombinant tissue plasminogen activator within 3 h of onset is only 16%.Given this fact,there is a pressing need for real‐time predictive tools,particularly for elderly individuals at home,that can provide early warnings for potential strokes.Methods:We collected continuous monitoring data from nonintrusive smart beds and multimodal temporal data from electronic medical records at the National Center for Neurological Disorders.The data included smart bed monitoring indicators,laboratory tests,nurse observations,and static data as potential predictors,with stroke as the outcome.We applied feature representation and feature selection techniques and then input the predictors into machine learning models.Additionally,deep learning models were used after preprocessing the irregular temporal data.Finally,we evaluated the performance of the stroke prediction models and assessed the importance of the features.We used continuously updated vital signs and clinical data during hospitalization to generate timely stroke risk alerts during the same period of admission.Results:A total of 37,041 samples were analyzed,of which 7020 patients were diagnosed with stroke.When only the smart bed features were used for prediction,the model achieved an area under the receiver operating characteristic curve(AUROC)of 0.59−0.63,with an accuracy ranging from 60%−65%.Among the four artificial intelligence algorithms,the random forest model demonstrated the best performance.After all the available features were incorporated,the AUROC increased to 0.94,and the accuracy improved to 92%.Conclusions:In this study,the occurrence of stroke was successfully identified by integrating multimodal temporal data from electronic medical records.Noncontact monitoring of respiration and heart rate offers a promising approach for daily stroke surveillance in home‐based populations,particularly for elderly individuals living alone.展开更多
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...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.展开更多
Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunolo...Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunological risk factors.It is thought that schizophrenia is exclusively linked to alterations in brain structure and function,while the relationship between the brain and many organs may lack sufficient attention.Increasing evidence indicates abnormalities of the interactions between the brain and many organs in patients with schizophrenia.Inter-organ crosstalk affects the onset,course,and management of schizophrenia.Besides,the complex relationship between autonomic nervous system,endocrine system,and immune system further facilitates the development of schizophrenia.The present review summarizes the relationships between the brain and multiple organ systems in schizophrenia,providing new perspectives on the underlying pathophysiological mechanisms of schizophrenia.展开更多
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 presen...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.展开更多
3-Hydroxy-3-methylglutaryl-CoA synthase(HMGS) is the first committed enzyme in the MVA pathway and involved in the biosynthesis of terpenes in Tripterygium wilfordii. The full-length cDNA and a 515 bp RNAi target frag...3-Hydroxy-3-methylglutaryl-CoA synthase(HMGS) is the first committed enzyme in the MVA pathway and involved in the biosynthesis of terpenes in Tripterygium wilfordii. The full-length cDNA and a 515 bp RNAi target fragment of TwHMGS were ligated into the p H7 WG2 D and p K7 GWIWG2 D vectors to respectively overexpress and silence, Tw HMGS was overexpressed and silenced in T. wilfordii suspension cells using biolistic-gun mediated transformation, which resulted in 2-fold increase and a drop to70% in the expression level compared to cells with empty vector controls. During Tw HMGS overexpression, the expression of TwHMGR, TwDXR and TwTPS7 v2 was significantly upregulated to the control. In the RNAi group, the expression of Tw HMGR,TwDXS, TwDXR and TwMCT visibly displayed downregulation to the control. The cells with TwHMGS overexpressed produced twice higher than the control value. These results proved that differential expression of Tw HMGS determined the production of triptolide in T.wilfordii and laterally caused different trends of relative gene expression in the terpene biosynthetic pathway. Finally, the substrate acetyl-Co A was docked into the active site of TwHMGS, suggesting the key residues including His247, Lys256 and Arg296 undergo electrostatic or H-bond interactions with acetyl-CoA.展开更多
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 ca...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.展开更多
Bipolar disorder(BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression.It affects more than 1% of the global population and is a leading cause of disabili...Bipolar disorder(BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression.It affects more than 1% of the global population and is a leading cause of disability in young people.Currently available treatments for BD are still fairly limited in terms of efficacy,with high rates of non-adherence,non-response,and undesirable side effects.Traditional Chinese medicine(TCM) has a long history and rich experience in stabilizing mania and improving quality of life.Aiming at rebalancing Yin and Yang in BD,therapy of replenishing Yin and regulating Yang(RYRY therapy) has been in clinical use for years in China.The present prospective,double-blind,randomized controlled trial is designed to investigate the efficacy and safety of RYRY therapy for bipolar mania and its possible mechanism from the point of regulating gut microbiota and anti-inflammation.A total of 60 eligible participants will be recruited from Beijing Anding Hospital.They will be randomized to either the study group or the control group in a ratio of 1∶1.Participants allocated to the study group will receive RYRY granule,while placebo granule will be applied in the control group.Participants in both groups will be prescribed conventional therapy for manic episode in BD.Four scheduled visits will be conducted over 4 weeks.Outcome measurements include Young Mania Rating Scale,TCM Symptom Pattern Rating Scale,Treatment Emergent Symptom Scale,levels of C-reactive protein,interleukin-6 and tumor necrosis factor-α and the gut microbial community profile of stool samples.Safety outcomes and adverse events will also be recorded.In this study,we set a number of scientific and objective assessments to evaluate the efficacy of RYRY therapy and study into its possible mechanism,hopefully offering clinicians an alternative approach to BD.展开更多
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 rela...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.展开更多
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 particip...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.展开更多
Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral method...Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral methods,most efforts on tree shrew behavior are limited to simple measures,resulting in the loss of much behavioral information.Methods:T o address this issue,we present a deep learning(DL)approach to achieve markerless pose estimation and recognize multiple spontaneous behaviors of tree shrews,including drinking,eating,resting,and staying in the dark house,etc.Results:T his high-t hroughput approach can monitor the home-cage activities of 16 tree shrews simultaneously over an extended period.Additionally,we demonstrated an innovative system with reliable apparatus,paradigms,and analysis methods for investigating food grasping behavior.The median duration for each bout of grasping was 0.20 s.Conclusion:T his study provides an efficient tool for quantifying and understand tree shrews'natural behaviors.展开更多
Background Acute ischaemic stroke,due to its high mortality and disability rates,imposes a significant economic and social burden worldwide.Typically,endovascular treatment within the therapeutic window is provided to...Background Acute ischaemic stroke,due to its high mortality and disability rates,imposes a significant economic and social burden worldwide.Typically,endovascular treatment within the therapeutic window is provided to salvage the ischaemic penumbra;however,even when recanalisation is successful during endovascular treatment,the clinical outcomes may still be disappointing.This highlights the necessity of further research,so as to discover better solutions to futile recanalisation and improve patient outcomes.Objective To investigate the efficacy and safety of Y-6 sublingual tablets(cilostazol and dexborneol)compared with a placebo in the treatment of patients with acute ischaemic stroke caused by large vessel occlusion.Method The efficacy and safety of Y-6 sublingual tablets in patients with acute ischaemic stroke are evaluated in a phase Ⅱ,randomised,double-blind,double-dummy,placebo-controlled,parallel clinical trial.Eligible patients having provided informed consent are randomised into five groups for a 28-day treatment period.The primary outcome is the percentage of patients achieving the modified Rankin Scale score of 0-1 at 90 days.Discussion The EFfects of Y-6 SUblingual Tablets for PaTients with AcUte Ischemic StRokE trial assesses whether Y-6 sublingual tablets are effective and safe in improving the clinical outcomes of patients with acute ischaemic stroke caused by large vessel occlusion.展开更多
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 ...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.展开更多
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 demonstrate...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.展开更多
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 ...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.展开更多
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 t...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.展开更多
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 ...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.展开更多
Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infe...Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.展开更多
Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying...Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying molecular mechanisms remain unclear.Here,we investigated how synaptic cell adhesion molecules(e.g.,nectin3)are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex(mPFC).Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77.One week later,the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory,simplified dendritic structure,and reduced spine density in the mPFC.Membrane localization of nectin3 was also altered,and was significantly correlated with behavioral performance.Furthermore,knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology.These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.展开更多
Type 1 diabetes mellitus(T1DM)-induced cognitive dysfunction is common,but its underlying mechanisms are still poorly understood.In this study,we found that knockout of conventional protein kinase C(cPKC)γsignificant...Type 1 diabetes mellitus(T1DM)-induced cognitive dysfunction is common,but its underlying mechanisms are still poorly understood.In this study,we found that knockout of conventional protein kinase C(cPKC)γsignificantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles,but did not affect the activities of GSK-3βand PP2A in the hippocampal neurons of T1DM mice.cPKCγdeficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice.Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγdeficiency in T1DM mice.Moreover,cPKCγdeficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro.The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor.In conclusion,these results indicated that cPKCγpromotes autophagy through the AMPK/mTOR signaling pathway,thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.展开更多
Gaming disorder has gained considerable attention worldwide,including in China[1],where epidemiological surveys have found that its prevalence is as high as 17%[2].The Bureau of Disease Control and Prevention run by t...Gaming disorder has gained considerable attention worldwide,including in China[1],where epidemiological surveys have found that its prevalence is as high as 17%[2].The Bureau of Disease Control and Prevention run by the National Health and Health Commission in China recently released an expert consensus[2]that systematically describes the definition,clinical presentation,assess-assessment,diagnosis,treatment,rehabilitation,and related areas of gaming disorder.展开更多
基金supported by the National Natural Science Foundation of China(72204169,82425101,82271516,81801187)Noncommunicable Chronic Diseases‐National Science and Technology Major Project(2023ZD0504800,2023ZD0504801,2023ZD0504802,2023ZD0504803,2023ZD0504804)+2 种基金Beijing Municipal Science&Technology Commission(Z231100004823036)Capital's Funds for Health Improvement and Research(2022‐2‐2045)National Key R&D Program of China(2024YFC3044800,2022YFF1501500,2022YFF1501501,2022YFF1501502,2022YFF1501503,2022YFF1501504,2022YFF1501505).
文摘Background:Stroke is the second leading cause of death and third leading cause of disability worldwide and is the leading cause of death and disability among adults in China,with its incidence rate continuing to rise.In China,the average age of firsttime stroke patients is 66.4 years,and the intravenous thrombolysis rate using recombinant tissue plasminogen activator within 3 h of onset is only 16%.Given this fact,there is a pressing need for real‐time predictive tools,particularly for elderly individuals at home,that can provide early warnings for potential strokes.Methods:We collected continuous monitoring data from nonintrusive smart beds and multimodal temporal data from electronic medical records at the National Center for Neurological Disorders.The data included smart bed monitoring indicators,laboratory tests,nurse observations,and static data as potential predictors,with stroke as the outcome.We applied feature representation and feature selection techniques and then input the predictors into machine learning models.Additionally,deep learning models were used after preprocessing the irregular temporal data.Finally,we evaluated the performance of the stroke prediction models and assessed the importance of the features.We used continuously updated vital signs and clinical data during hospitalization to generate timely stroke risk alerts during the same period of admission.Results:A total of 37,041 samples were analyzed,of which 7020 patients were diagnosed with stroke.When only the smart bed features were used for prediction,the model achieved an area under the receiver operating characteristic curve(AUROC)of 0.59−0.63,with an accuracy ranging from 60%−65%.Among the four artificial intelligence algorithms,the random forest model demonstrated the best performance.After all the available features were incorporated,the AUROC increased to 0.94,and the accuracy improved to 92%.Conclusions:In this study,the occurrence of stroke was successfully identified by integrating multimodal temporal data from electronic medical records.Noncontact monitoring of respiration and heart rate offers a promising approach for daily stroke surveillance in home‐based populations,particularly for elderly individuals living alone.
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘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.
基金Supported by Beijing Traditional Chinese Medicine Scientific and Technological Development Fund Project,No.BJZYYB-2023-66Beijing Natural Science Foundation,No.7212050the Capital’s Funds for Health Improvement and Research,No.2020-4-2126.
文摘Schizophrenia is characterized by psychotic symptoms,negative symptoms,and cognitive deficits,profoundly affecting individuals and their families.The etiology is multifactorial,involving genetic,endocrine,and immunological risk factors.It is thought that schizophrenia is exclusively linked to alterations in brain structure and function,while the relationship between the brain and many organs may lack sufficient attention.Increasing evidence indicates abnormalities of the interactions between the brain and many organs in patients with schizophrenia.Inter-organ crosstalk affects the onset,course,and management of schizophrenia.Besides,the complex relationship between autonomic nervous system,endocrine system,and immune system further facilitates the development of schizophrenia.The present review summarizes the relationships between the brain and multiple organ systems in schizophrenia,providing new perspectives on the underlying pathophysiological mechanisms of schizophrenia.
基金This work was supported by Nation Science and Technology Major Projects for Major New Drugs Innovation and Development(2018ZX09711003-004-002 to L.C.)Ministry of Science and Technology of China National Key R&D Programs(2018YFA0506903 to L.C.)National Natural Science Foundation of China grants(91857108 to L.C.).
文摘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.
基金supported by the National Natural Science Foundation of China(No.81773830)Beijing Natural Science Foundation Program+3 种基金Scientific Research Key Program of Beijing Municipal Commission of Education(No.KZ201710025022)the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan(No.CIT&TCD20170324)National Program for Special Support of Eminent ProfessionalsKey project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)
文摘3-Hydroxy-3-methylglutaryl-CoA synthase(HMGS) is the first committed enzyme in the MVA pathway and involved in the biosynthesis of terpenes in Tripterygium wilfordii. The full-length cDNA and a 515 bp RNAi target fragment of TwHMGS were ligated into the p H7 WG2 D and p K7 GWIWG2 D vectors to respectively overexpress and silence, Tw HMGS was overexpressed and silenced in T. wilfordii suspension cells using biolistic-gun mediated transformation, which resulted in 2-fold increase and a drop to70% in the expression level compared to cells with empty vector controls. During Tw HMGS overexpression, the expression of TwHMGR, TwDXR and TwTPS7 v2 was significantly upregulated to the control. In the RNAi group, the expression of Tw HMGR,TwDXS, TwDXR and TwMCT visibly displayed downregulation to the control. The cells with TwHMGS overexpressed produced twice higher than the control value. These results proved that differential expression of Tw HMGS determined the production of triptolide in T.wilfordii and laterally caused different trends of relative gene expression in the terpene biosynthetic pathway. Finally, the substrate acetyl-Co A was docked into the active site of TwHMGS, suggesting the key residues including His247, Lys256 and Arg296 undergo electrostatic or H-bond interactions with acetyl-CoA.
基金supported by the National Key Research and Development Program of China(2017YFA0105203,2017YFA0105201)National Science Foundation of China(31771076,81925011)+2 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDB32040201)Beijing Academy of Artificial IntelligenceKey-Area Research and Development Program of Guangdong Province(2019B030335001)。
文摘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.
基金Supported by Beijing Municipal Administration of Hospitals Incubating Program(No.PZ2021031),which plays no role in the design of the studycollection,analysis,and interpretation of data,and in writing the manuscript。
文摘Bipolar disorder(BD) is a chronic and recurrent disorder characterized by biphasic mood episodes of mania or hypomania and depression.It affects more than 1% of the global population and is a leading cause of disability in young people.Currently available treatments for BD are still fairly limited in terms of efficacy,with high rates of non-adherence,non-response,and undesirable side effects.Traditional Chinese medicine(TCM) has a long history and rich experience in stabilizing mania and improving quality of life.Aiming at rebalancing Yin and Yang in BD,therapy of replenishing Yin and regulating Yang(RYRY therapy) has been in clinical use for years in China.The present prospective,double-blind,randomized controlled trial is designed to investigate the efficacy and safety of RYRY therapy for bipolar mania and its possible mechanism from the point of regulating gut microbiota and anti-inflammation.A total of 60 eligible participants will be recruited from Beijing Anding Hospital.They will be randomized to either the study group or the control group in a ratio of 1∶1.Participants allocated to the study group will receive RYRY granule,while placebo granule will be applied in the control group.Participants in both groups will be prescribed conventional therapy for manic episode in BD.Four scheduled visits will be conducted over 4 weeks.Outcome measurements include Young Mania Rating Scale,TCM Symptom Pattern Rating Scale,Treatment Emergent Symptom Scale,levels of C-reactive protein,interleukin-6 and tumor necrosis factor-α and the gut microbial community profile of stool samples.Safety outcomes and adverse events will also be recorded.In this study,we set a number of scientific and objective assessments to evaluate the efficacy of RYRY therapy and study into its possible mechanism,hopefully offering clinicians an alternative approach to BD.
基金Supported by the National Natural Science Foundation of China,No.81971250 and No.82171501Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support,No.ZLRK202335Early Psychosis Cohort Program of Beijing Anding Hospital,No.ADDL-03.
文摘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.
文摘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.
基金supported by grants from the National Key Research and Development Program of China(2023YFF0724902)the China Postdoctoral Science Foundation(2020?M670027,2023TQ0183)the Local Standards Research of BeiJing Laboratory Tree Shrew(CHYX-2023-DGB001)。
文摘Background:Q uantifying the rich home-c age activities of tree shrews provides a reliable basis for understanding their daily routines and building disease models.However,due to the lack of effective behavioral methods,most efforts on tree shrew behavior are limited to simple measures,resulting in the loss of much behavioral information.Methods:T o address this issue,we present a deep learning(DL)approach to achieve markerless pose estimation and recognize multiple spontaneous behaviors of tree shrews,including drinking,eating,resting,and staying in the dark house,etc.Results:T his high-t hroughput approach can monitor the home-cage activities of 16 tree shrews simultaneously over an extended period.Additionally,we demonstrated an innovative system with reliable apparatus,paradigms,and analysis methods for investigating food grasping behavior.The median duration for each bout of grasping was 0.20 s.Conclusion:T his study provides an efficient tool for quantifying and understand tree shrews'natural behaviors.
基金supported by grants from the National Natural Science Foundation of China(No.82425101)Beijing Municipal Science&Technology Commission(No.Z231100004823036)+8 种基金Capital's Funds for Health Improvement and Research(2022-2-2045)National Key R&D Program of China(2024YFC3044800,2022YFF1501500,2022YFF1501501,2022YFF1501502,2022YFF1501503,2022YFF1501504,2022YFF1501505)Youth Beijing Scholar Program(No.010)Beijing Laboratory of Oral Health(PXM2021_014226_000041)Beijing Talent Project-Class A:Innovation and Development(No.2018A12)National Ten-Thousand Talent Plan"-Leadership of Scientific and Technological InnovationNational Key R&D Program of China(No.2017YFC1307900,2017YFC1307905)Beijing Outstanding Young Scientist Program(No.BJJWZYJH01201910025030)Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0504800,2023ZD0504801,2023ZD0504802,2023ZD0504803,2023ZD0504804)。
文摘Background Acute ischaemic stroke,due to its high mortality and disability rates,imposes a significant economic and social burden worldwide.Typically,endovascular treatment within the therapeutic window is provided to salvage the ischaemic penumbra;however,even when recanalisation is successful during endovascular treatment,the clinical outcomes may still be disappointing.This highlights the necessity of further research,so as to discover better solutions to futile recanalisation and improve patient outcomes.Objective To investigate the efficacy and safety of Y-6 sublingual tablets(cilostazol and dexborneol)compared with a placebo in the treatment of patients with acute ischaemic stroke caused by large vessel occlusion.Method The efficacy and safety of Y-6 sublingual tablets in patients with acute ischaemic stroke are evaluated in a phase Ⅱ,randomised,double-blind,double-dummy,placebo-controlled,parallel clinical trial.Eligible patients having provided informed consent are randomised into five groups for a 28-day treatment period.The primary outcome is the percentage of patients achieving the modified Rankin Scale score of 0-1 at 90 days.Discussion The EFfects of Y-6 SUblingual Tablets for PaTients with AcUte Ischemic StRokE trial assesses whether Y-6 sublingual tablets are effective and safe in improving the clinical outcomes of patients with acute ischaemic stroke caused by large vessel occlusion.
基金supported by the National Key Research and Development Program of China(Grant No.2020YFA0803700)the National Natural Science Foundation of China(Grant Nos.91639108,81770272,and 81970425)+1 种基金the Beijing Natural Science Foundation(Grant No.7212044)the Beijing Hospital Authority Youth Program(Grant No.QML20190306)。
文摘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.
基金supported by the Chongqing Science and Technology CommitteeNatural Science Foundation of Chongqing,No.cstc2021jcyj-msxmX0065 (to YL)。
文摘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.
文摘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.
基金financially supported by the Beijing Hospital Management Center“Dengfeng”plan[DFL20191901]。
文摘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.
基金supported by the National Natural Science Foundation of China (No. 61672070, 61501007, 11675199, 61572004 and 81501155)the Key Project of Beijing Municipal Education Commission (No. KZ201910005008)+3 种基金general project of science and technology project of Beijing Municipal Education Commission (No. KM201610005023)the Beijing Municipal Natural Science Foundation (No. 4182005)Clinical Technology Innovation Program of Beijing Municipal Administration of Hospitals (No. XMLX201805)Beijing Municipal Science & Tech Commission (No. Z171100000117004)
文摘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.
基金supported by the National Basic Research Program of China(2020YFA0804000,2020YFC0842000,2020YFA0112200,2021YFC2301703)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010100)+6 种基金Special Associate Research Program of the Chinese Academy of Sciences(E1290601)National Natural Science Foundation of China(32122037,81891001,32192411,32100512,U1902215)Collaborative Research Fund of the Chinese Institute for Brain Research,Beijing(2020-NKX-PT-03)CAS Project for Young Scientists in Basic Research(YSBR-013)Young Elite Scientist Sponsorship Program by the China Association for Science and Technology(2020QNRC001)National Resource Center for Non-Human Primates。
文摘Infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs.However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000single-nucleus transcriptomes of the lung, liver,kidney, and cerebral cortex in rhesus macaques(Macaca mulatta) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multiorgan dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019(COVID-19).Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway,which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy(an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection,which may facilitate the development of therapeutic interventions for COVID-19.
基金supported by the National Natural Science Foundation of China(81401129,81571321,81630031,and 81571312)the Peking University Medicine Seed Fund for Interdisciplinary Research (BMU2017MX021)+1 种基金the National Key Basic Research Program of China (2015CB856401)the Beijing Brain Project (Z171100000117016)。
文摘Chronic stress may disrupt the normal neurodevelopmental trajectory of the adolescent brain(especially the prefrontal cortex) and contribute to the pathophysiology of stress-related mental illnesses,but the underlying molecular mechanisms remain unclear.Here,we investigated how synaptic cell adhesion molecules(e.g.,nectin3)are involved in the effects of adolescent chronic stress on mouse medial prefrontal cortex(mPFC).Male C57BL/6N mice were subjected to chronic social instability stress from postnatal days 29 to 77.One week later,the mice exposed to chronic stress exhibited impaired social recognition and spatial working memory,simplified dendritic structure,and reduced spine density in the mPFC.Membrane localization of nectin3 was also altered,and was significantly correlated with behavioral performance.Furthermore,knocking down mPFC nectin3 expression by adeno-associated virus in adolescent mice reproduced the stress-induced changes in behavior and mPFC morphology.These results support the hypothesis that nectin3 is a potential mediator of the effects of adolescent chronic stress on prefrontal structural and functional abnormalities.
基金This work was supported by the Beijing Natural Science Foundation(7192016 and 7222064)the Scientific Research Common Program of Beijing Municipal Commission of Education(KM201910025029)the National Natural Science Foundation of China(82071539 and 31972911).
文摘Type 1 diabetes mellitus(T1DM)-induced cognitive dysfunction is common,but its underlying mechanisms are still poorly understood.In this study,we found that knockout of conventional protein kinase C(cPKC)γsignificantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles,but did not affect the activities of GSK-3βand PP2A in the hippocampal neurons of T1DM mice.cPKCγdeficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice.Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγdeficiency in T1DM mice.Moreover,cPKCγdeficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro.The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor.In conclusion,these results indicated that cPKCγpromotes autophagy through the AMPK/mTOR signaling pathway,thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.
基金supported by the National Science and Technology Major Project for Investigational New Drug of China (2018ZX09201-014)the Beijing Municipal Science and Technology Commission,China (No. Z181100001518005)the University of Macao (MYRG201900066-FHS)。
文摘Gaming disorder has gained considerable attention worldwide,including in China[1],where epidemiological surveys have found that its prevalence is as high as 17%[2].The Bureau of Disease Control and Prevention run by the National Health and Health Commission in China recently released an expert consensus[2]that systematically describes the definition,clinical presentation,assess-assessment,diagnosis,treatment,rehabilitation,and related areas of gaming disorder.
