With the socioeconomic development and the acceleration of the ageing process of the population, the incidence rates of mental disorders and psycho-behavioural problems have become higher and higher worldwide. So far,...With the socioeconomic development and the acceleration of the ageing process of the population, the incidence rates of mental disorders and psycho-behavioural problems have become higher and higher worldwide. So far, the disease burden caused by mental disorders has ranked second in the world.1 In China, the disease burden caused by mental disorders accounts for 13% of all non-communicable diseases burden.2 Hence, mental health has become a major public health problem and social problem. In order to promote mental health, the Chinese government has promulgated a series of policies and regulations, as well as reform measures. Moreover, the upcoming 'China Brain Project' will also focus on some mental disorders such as autism, depression and dementia to improve mental health research in China.展开更多
BACKGROUNDIn the post-pandemic era, the emergence of sporadic cases of coronavirus disease 2019 (COVID-19) and the scale of the pandemic are unpredictable. Therefore, the impact ofsporadic cases of COVID-19 and isolat...BACKGROUNDIn the post-pandemic era, the emergence of sporadic cases of coronavirus disease 2019 (COVID-19) and the scale of the pandemic are unpredictable. Therefore, the impact ofsporadic cases of COVID-19 and isolation measures on mental health and sleep in different groupsof people need to be analyzed.AIMTo clarify the severity of psychological problems and insomnia of staff and community residentsaround a hospital with sporadic cases of COVID-19, and their relationship with quarantinelocation and long-term changes.METHODSA cross-sectional survey was conducted on community residents and medical staff. Many of thesemedical staff had been subjected to different places of quarantine. Community residents did notexperience quarantine. Hospital anxiety and depression scale (HADS), acute stress disorder scale(ASDS) and insomnia severity index (ISI) were used to evaluate anxiety and depression, acutestress disorder symptoms, and the severity of insomnia. Additionally, we conducted a 1-yearfollow-up study on medical staff, with related scales measurement immediately after and one yearafter the 2-wk quarantine period.RESULTSWe included 406 medical staff and 226 community residents. The total scores of ISI and subscale inHADS of community residents were significantly higher than that of medical staff. Furtheranalysis of medical staff who experienced quarantine showed that 134 were quarantined in hotels,70 in hospitals and 48 at home. Among all subjects, the proportions of HADS, ASDS and ISI scoresabove normal cutoff value were 51.94%, 19.17% and 31.11%, respectively. Multivariable logisticregression analysis found that subjects with higher total ASDS scores had a greater risk to developanxiety and depression. The total ISI score for medical staff in hotel quarantine was significantlyhigher than those in home quarantine. Total 199 doctors and nurses who completed the 1-yearfollow-up study. Compared with baseline, HADS and ASDS scores decreased significantly oneyear after the end of quarantine, while ISI scores did not change significantly.CONCLUSIONSporadic COVID-19 cases had a greater psychological impact on residents in surroundingcommunities, mainly manifested as insomnia and depressive symptoms. Hotel quarantineaggravated the severity of insomnia in medical staff, whose symptoms lasted ≥ 1 year.展开更多
Background Healthcare workers fighting against the coronavirus disease 2019(COVID-19)pandemic are under tremendous pressure,which puts them at an increased risk of developing psychological problems.Aims This study aim...Background Healthcare workers fighting against the coronavirus disease 2019(COVID-19)pandemic are under tremendous pressure,which puts them at an increased risk of developing psychological problems.Aims This study aimed to investigate the prevalence of psychological problems in different healthcare workers(ie,physicians,medical residents,nurses,technicians and public health professionals)during the COVID-19 pandemic in China and explore factors that are associated with the onset of psychological problems in this population during this public health crisis.Methods A cross-sectional,web-based survey was conducted in February 2020 among healthcare workers during the COVID-19 pandemic.Psychological problems were assessed using the Generalized Anxiety Disorder Scale,Patient Health Questionnaire and Insomnia Severity Index.Logistic regression analyses were used to explore the factors that were associated with psychological problems.Results The prevalence of symptoms of anxiety,depression,insomnia and the overall psychological problems in healthcare workers during the COVID-19 pandemic in China was 46.04%,44.37%,28.75%and 56.59%,respectively.The prevalence of the overall psychological problems in physicians,medical residents,nurses,technicians and public health professionals was 60.35%,50.82%,62.02%,57.54%and 62.40%,respectively.Compared with healthcare workers who did not participate in front-line work,front-line healthcare workers had a higher risk of anxiety,insomnia and overall psychological problems.In addition,attention to negative or neutral information about the pandemic,receiving negative feedback from families and friends who joined front-line work,and unwillingness to join front-line work if given a free choice were three major factors for these psychological problems.Conclusions Psychological problems are pervasive among healthcare workers during the COVID-19 pandemic.Receiving negative information and participating in front-line work appear to be.important risk factors for psychological problems.The psychological health of different healthcare workers should be protected during the COVID-19 pandemic with timely interventions and proper information feedback.展开更多
Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack ...Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting...Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting against these stealthy bacteria has been a longstanding challenge.Here,a system of stimuli-responsive lactoferrin(Lf)nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin(Rif)(Rif@Lf NPs)for enhanced infection therapy through targeted elimination of intracellular bacteria.Compared to Rif@BSA NPs,the Rif@Lf NPs can specifically target macrophages infected by bacteria,thus increasing the accumulation of Rif within macrophages.Subsequently,Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redoxresponsive manner.Combined with the antibacterial activities of Lf and Rif,the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms.As a result,the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection,sepsis,and bacterial keratitis.Taken together,the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.展开更多
The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent year...The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.展开更多
To the editor:Mood disorders(MD)are serious mental illnesses that commonly affect adolescents,leading to a high incidence of suicidal behaviour.1 In China,the suicide attempt(SA)rate for adolescents with MD is 51.96%,...To the editor:Mood disorders(MD)are serious mental illnesses that commonly affect adolescents,leading to a high incidence of suicidal behaviour.1 In China,the suicide attempt(SA)rate for adolescents with MD is 51.96%,2 and over 500000 adolescent SA are reported annually in the USA due to depression.3 Risk factors for SA include gender,hormone levels,family conflict and,particularly,negative cognitive styles such as rumination.展开更多
Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disord...Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder.However,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well understood.This reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood states.We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood state.We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects.Finally,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.展开更多
Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain...Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.展开更多
Increasing evidences show that aberrant subchondral bone remodeling plays an important role in the development of osteoarthritis(OA).However,how subchondral bone formation is activated and the mechanism by which incre...Increasing evidences show that aberrant subchondral bone remodeling plays an important role in the development of osteoarthritis(OA).However,how subchondral bone formation is activated and the mechanism by which increased subchondral bone turnover promotes cartilage degeneration during OA remains unclear.Here,we show that the mechanistic target of rapamycin complex 1(mTORC1)pathway is activated in subchondral bone preosteoblasts(Osterix+)from OA patients and mice.Constitutive activation of mTORC1 in preosteoblasts by deletion of the mTORC1 upstream inhibitor,tuberous sclerosis 1,induced aberrant subchondral bone formation,and sclerosis with little-to-no effects on articular cartilage integrity,but accelerated posttraumatic OA development in mice.In contrast,inhibition of mTORC1 in preosteoblasts by disruption of Raptor(mTORC1-specific component)reduced subchondral bone formation and cartilage degeneration,and attenuated post-traumatic OA in mice.Mechanistically,mTORC1 activation promoted preosteoblast expansion and Cxcl12 secretion,which induced subchondral bone remodeling and cartilage degeneration during OA.A Cxcl12-neutralizing antibody reduced cartilage degeneration and alleviated OA in mice.Altogether,these findings demonstrate that mTORC1 activation in subchondral preosteoblasts is not sufficient to induce OA,but can induce aberrant subchondral bone formation and secrete of Cxcl12 to accelerate disease progression following surgical destabilization of the joint.Pharmaceutical inhibition of the pathway presents a promising therapeutic approach for OA treatment.展开更多
Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cogni...Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population. Aim To provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES. Methods An independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size. Results 56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as 'high quality' according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=-1.60,95% Cl -1.82 to -1.38,厂=67%) and all seven cognitive domains, with the SMD ranging from -0.87 to -1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=-1.90), Trail Making Test (TMT)(SMD=-1.36), Continuous Performance Test-Identical Pairs (SMD=-1.33), Hopkins Verbal Learning Test (SMD=-1.24), Brief Visuospatial Memory Test (SMD=-1.18), Mazes (SMD=-1.16), Category Fluency (SMD=-1.01), Spatial Span (SMD=-0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=-0.38). Conclusions Our meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.展开更多
Radiation therapy is a standard treatment for head and neck tumors.However,patients often exhibit cognitive impairments following radiation therapy.Previous studies have revealed that hippocampal dysfunction,specifica...Radiation therapy is a standard treatment for head and neck tumors.However,patients often exhibit cognitive impairments following radiation therapy.Previous studies have revealed that hippocampal dysfunction,specifically abnormal hippocampal neurogenesis or neuroinflammation,plays a key role in radiation-induced cognitive impairment.However,the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly characterized.We found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/min.Furthermore,we observed a remarkable reduction in spike firing and excitatory synaptic input,as well as greatly enhanced inhibitory inputs,in hippocampal CA1 pyramidal neurons.Corresponding to the electrophysiological adaptation,we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of VGAT.Furthermore,in irradiated mice,long-term potentiation in the hippocampus was weakened and GluR1 expression was inhibited.These findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.展开更多
There is an increasing heavy disease burden of major depressive disorder(MDD)globally.Both high diagnostic heterogeneity and complicated pathological mechanisms of MDD pose significant challenges.There is much evidenc...There is an increasing heavy disease burden of major depressive disorder(MDD)globally.Both high diagnostic heterogeneity and complicated pathological mechanisms of MDD pose significant challenges.There is much evidence to support anhedonia as a core feature of MDD.In the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition,anhedonia is further emphasised as a key item in the diagnosis of major depression with melancholic features.Anhedonia is a multifaceted symptom that includes deficits in various aspects of reward processing,such as anticipatory anhedonia,consummatory anhedonia,and decision-making anhedonia.Anhedonia is expected to become an important clinicopathological sign for predicting the treatment outcome of MDD and assisting clinical decision making.However,the precise neurobiological mechanisms of anhedonia in MDD are not clearly understood.In this paper,we reviewed(1)the current understanding of the link between anhedonia and MDD;(2)the biological basis of the pathological mechanism of anhedonia in MDD;and(3)challenges in research on the pathological mechanisms of anhedonia in MDD.A more in-depth understanding of anhedonia associated with MDD will improve the diagnosis,prediction,and treatment of patients with MDD in the future.展开更多
Purpose: The purpose of this study was to determine the effects of acute exercise on motor response inhibition using both behavioral and electrophysiological approaches. Methods: The P3 and N1 event-related potenti...Purpose: The purpose of this study was to determine the effects of acute exercise on motor response inhibition using both behavioral and electrophysiological approaches. Methods: The P3 and N1 event-related potential (ERP) components were recorded while performing a stop-signal task in 21 college students following a moderately intense acute exercise bout for 30 min and a sedentary control session that involved reading. Results: Acute exercise induced a shorter stop signal response time (SSRT) as compared to control; however, the go response time (Go RT) remained unchanged. In examining the ERP data, acute exercise increased both P3 amplitude and latency but did not affect the N1 component. Conclusion: Acute exercise has a selective and beneficial effect on cognitive function, specifically affecting the motor response inhibition aspect of executive function. Furthermore, acute exercise predominately impacts later stages of information processing during motor response inhibition, which may lead to an increase in attentional resource allocation and confer the ability to successfully withhold a response to achieve motor response inhibition.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has caused major public panic in China.Pregnant women may be more vulnerable to stress,which may cause them to have psychological problems.AIM To explore the e...BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has caused major public panic in China.Pregnant women may be more vulnerable to stress,which may cause them to have psychological problems.AIM To explore the effects of perceived family support on psychological distress in pregnant women during the COVID-19 pandemic.METHODS A total of 2232 subjects were recruited from three cities in China.Through the online surveys,information on demographic data and health status during pregnancy were collected.Insomnia severity index,generalized anxiety disorder 7-item scale,patient health questionnaire-9,somatization subscale of the symptom check list 90 scale,and posttraumatic stress disorder checklist were used to assess the psychological distress.RESULTS A total of 1015(45.4%)women reported having at least one psychological distress.The women who reported having inadequate family support were more likely to suffer from multiple psychological distress(≥2 psychological distress)than women who received adequate family support.Among the women who reported less family support,41.8%reported depression,31.1%reported anxiety,8.2%reported insomnia,13.3%reported somatization and 8.9%reported posttraumatic stress disorder(PTSD),which were significantly higher than those who received strong family support.Perceived family support level was negatively correlated with depressive symptoms(r=-0.118,P<0.001),anxiety symptoms(r=-0.111,P<0.001),and PTSD symptoms(r=-0.155,P<0.001).CONCLUSION Family support plays an important part on pregnant women’s mental health during the COVID-19 pandemic.Better family support can help improve the mental health of pregnant women.展开更多
The traditional "brain-derived neurotrophic factor (BDNF) hypothesis of depression" proposes that impairment of the BDNF signaling pathway in the hippocampus and prefrontal cortex participates in the pathophysiolo...The traditional "brain-derived neurotrophic factor (BDNF) hypothesis of depression" proposes that impairment of the BDNF signaling pathway in the hippocampus and prefrontal cortex participates in the pathophysiology of depression, and antidepressants act by recovering/enhancing BDNF signal transduction. Recent studies have suggested that BDNF signaling pathways exert more diverse and complex effects on depression onset and antidepressant therapy than originally thought, which include: (1) inhibition of the BDNF-TrkB signaling pathway in the hippocampus and/or prefrontal cortex does not induce the depression-like behavioral phenotype, but significantly diminishes therapeutic effects, which suggests that the BDNF-TrkB signaling pathway lacks direct or key effects on occurrence of emotional disorders, whereas an intact and normal BDNF-TrkB signaling pathway is necessary for antidepressant therapy. (2) The BDNF-TrkB signaling pathway exhibits opposite regulatory effects on depressive behavior in the hippocampus-prefrontal cortex network and mesolimbic system, which suggests that BDNF regulates emotion by affecting the emotion-related neural network, but not a single brain region. (3) The BDNF-TrkB and proBDNF-p75Nm signaling pathways in the brain, respectively, enhance and suppress hippocampal neural plasticity, which demonstrated that different BDNF signaling pathways interact and restrict each other in the regulation of neural plasticity and emotional behaviors. (4) BDNF gene polymorphism might be associated with susceptibility to depression. These new findings extend our understanding of neuronal pathways and mechanisms of action of BDNF signaling and contribute to improved views to traditional "neurotrophic factor hypothesis of depression".展开更多
With the largest ageing population in the world,China is faced with the huge chal-lenge of dementia.-However,previously reported estimates on the prevalence of dementia among Chinese older adults were inconsistent,var...With the largest ageing population in the world,China is faced with the huge chal-lenge of dementia.-However,previously reported estimates on the prevalence of dementia among Chinese older adults were inconsistent,varying from 2%to 13%.5°It is crucial for dementia prevention to determine the number of cases that could be delayed or prevented,but how to do this remains unclear.To address these research gaps,we aimed to provide population estimates of the prevalence of dementia in China and estimate the population attributable fractions(PAFs)of potentially modifiable risk factors.展开更多
Dendrites play irreplaceable roles in the nerve conduction pathway and are vulnerable to various insults.Peripheral axotomy of motor neurons results in the retraction of dendritic arbors,and the dendritic arbor can be...Dendrites play irreplaceable roles in the nerve conduction pathway and are vulnerable to various insults.Peripheral axotomy of motor neurons results in the retraction of dendritic arbors,and the dendritic arbor can be re-expanded when reinnervation is allowed.RhoA is a target that regulates the cytoskeleton and promotes neuronal survival and axon regeneration.However,the role of RhoA in dendrite degeneration and regeneration is unknown.In this study,we explored the potential role of RhoA in dendrites.A line of motor neuronal conditional knockout mice was developed by crossbreeding HB9~(Cre+)mice with RhoA~(flox/flox)mice.We established two models for assaying dendrite degeneration and regeneration,in which the brachial plexus was transection or crush injured,respectively.We found that at 28 days after brachial plexus transection,the density,complexity,and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice were slightly decreased compared with that in Cre mice.Dendrites underwent degeneration at 7 and 14 days after brachial plexus transection and recovered at 28–56 days.The density,complexity,and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice recovered compared with results in Cre mice.These findings suggest that RhoA knockout in motor neurons attenuates dendrite degeneration and promotes dendrite regeneration after peripheral nerve injury.展开更多
Wallerian degeneration,the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury,is essential for creating a permissive microenvironment for nerve regeneration,and involves cy...Wallerian degeneration,the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury,is essential for creating a permissive microenvironment for nerve regeneration,and involves cytoskeletal reconstruction.However,it is unclear whether microtubule dynamics play a role in this process.To address this,we treated cultured sciatic nerve explants,an in vitro model of Wallerian degeneration,with the microtubule-targeting agents paclitaxel and nocodazole.We found that paclitaxel-induced microtubule stabilization promoted axon and myelin degeneration and Schwann cell dedifferentiation,whereas nocodazole-induced microtubule destabilization inhibited these processes.Evaluation of an in vivo model of peripheral nerve injury showed that treatment with paclitaxel or nocodazole accelerated or attenuated axonal regeneration,as well as functional recovery of nerve conduction and target muscle and motor behavior,respectively.These results suggest that microtubule dynamics participate in peripheral nerve regeneration after injury by affecting Wallerian degeneration.This study was approved by the Animal Care and Use Committee of Southern Medical University,China(approval No.SMUL2015081) on October 15,2015.展开更多
文摘With the socioeconomic development and the acceleration of the ageing process of the population, the incidence rates of mental disorders and psycho-behavioural problems have become higher and higher worldwide. So far, the disease burden caused by mental disorders has ranked second in the world.1 In China, the disease burden caused by mental disorders accounts for 13% of all non-communicable diseases burden.2 Hence, mental health has become a major public health problem and social problem. In order to promote mental health, the Chinese government has promulgated a series of policies and regulations, as well as reform measures. Moreover, the upcoming 'China Brain Project' will also focus on some mental disorders such as autism, depression and dementia to improve mental health research in China.
基金funded by the Special Research Project for the Non-profit Public Service of the Ministry of Health(Grant 201202022)the National ‘‘Twelfth Five-Year Plan’’ for Science&Technology supported by the Ministry of Science and Technology(Grant 2012BAI01B01)
基金Supported by the Beijing Municipal Science&Technology Commission,No. Z191107006619091National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital),No. NCRC2020M07National Natural Science Foundation of China,No. 81871071
文摘BACKGROUNDIn the post-pandemic era, the emergence of sporadic cases of coronavirus disease 2019 (COVID-19) and the scale of the pandemic are unpredictable. Therefore, the impact ofsporadic cases of COVID-19 and isolation measures on mental health and sleep in different groupsof people need to be analyzed.AIMTo clarify the severity of psychological problems and insomnia of staff and community residentsaround a hospital with sporadic cases of COVID-19, and their relationship with quarantinelocation and long-term changes.METHODSA cross-sectional survey was conducted on community residents and medical staff. Many of thesemedical staff had been subjected to different places of quarantine. Community residents did notexperience quarantine. Hospital anxiety and depression scale (HADS), acute stress disorder scale(ASDS) and insomnia severity index (ISI) were used to evaluate anxiety and depression, acutestress disorder symptoms, and the severity of insomnia. Additionally, we conducted a 1-yearfollow-up study on medical staff, with related scales measurement immediately after and one yearafter the 2-wk quarantine period.RESULTSWe included 406 medical staff and 226 community residents. The total scores of ISI and subscale inHADS of community residents were significantly higher than that of medical staff. Furtheranalysis of medical staff who experienced quarantine showed that 134 were quarantined in hotels,70 in hospitals and 48 at home. Among all subjects, the proportions of HADS, ASDS and ISI scoresabove normal cutoff value were 51.94%, 19.17% and 31.11%, respectively. Multivariable logisticregression analysis found that subjects with higher total ASDS scores had a greater risk to developanxiety and depression. The total ISI score for medical staff in hotel quarantine was significantlyhigher than those in home quarantine. Total 199 doctors and nurses who completed the 1-yearfollow-up study. Compared with baseline, HADS and ASDS scores decreased significantly oneyear after the end of quarantine, while ISI scores did not change significantly.CONCLUSIONSporadic COVID-19 cases had a greater psychological impact on residents in surroundingcommunities, mainly manifested as insomnia and depressive symptoms. Hotel quarantineaggravated the severity of insomnia in medical staff, whose symptoms lasted ≥ 1 year.
基金grants from the Beijing Natural Science Foundation(No.7194336)Special Research Fund of PKUHSC for Prevention and Control of COVID-19(No.BMU2020HKYZX008)the National Natural Science Foundation of China(No.81761128036,81821092 and 31900805).
文摘Background Healthcare workers fighting against the coronavirus disease 2019(COVID-19)pandemic are under tremendous pressure,which puts them at an increased risk of developing psychological problems.Aims This study aimed to investigate the prevalence of psychological problems in different healthcare workers(ie,physicians,medical residents,nurses,technicians and public health professionals)during the COVID-19 pandemic in China and explore factors that are associated with the onset of psychological problems in this population during this public health crisis.Methods A cross-sectional,web-based survey was conducted in February 2020 among healthcare workers during the COVID-19 pandemic.Psychological problems were assessed using the Generalized Anxiety Disorder Scale,Patient Health Questionnaire and Insomnia Severity Index.Logistic regression analyses were used to explore the factors that were associated with psychological problems.Results The prevalence of symptoms of anxiety,depression,insomnia and the overall psychological problems in healthcare workers during the COVID-19 pandemic in China was 46.04%,44.37%,28.75%and 56.59%,respectively.The prevalence of the overall psychological problems in physicians,medical residents,nurses,technicians and public health professionals was 60.35%,50.82%,62.02%,57.54%and 62.40%,respectively.Compared with healthcare workers who did not participate in front-line work,front-line healthcare workers had a higher risk of anxiety,insomnia and overall psychological problems.In addition,attention to negative or neutral information about the pandemic,receiving negative feedback from families and friends who joined front-line work,and unwillingness to join front-line work if given a free choice were three major factors for these psychological problems.Conclusions Psychological problems are pervasive among healthcare workers during the COVID-19 pandemic.Receiving negative information and participating in front-line work appear to be.important risk factors for psychological problems.The psychological health of different healthcare workers should be protected during the COVID-19 pandemic with timely interventions and proper information feedback.
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
基金support from the National Natural Science Foundation of China(Nos.22275081,82372117)Guangzhou Science and Technology Bureau(202206010068)China Postdoctoral Science Foundation(2022M711532 and 2022T150302).
文摘Intracellular bacteria can multiply inside host cells and manipulate their biology,and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation.Fighting against these stealthy bacteria has been a longstanding challenge.Here,a system of stimuli-responsive lactoferrin(Lf)nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin(Rif)(Rif@Lf NPs)for enhanced infection therapy through targeted elimination of intracellular bacteria.Compared to Rif@BSA NPs,the Rif@Lf NPs can specifically target macrophages infected by bacteria,thus increasing the accumulation of Rif within macrophages.Subsequently,Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redoxresponsive manner.Combined with the antibacterial activities of Lf and Rif,the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms.As a result,the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection,sepsis,and bacterial keratitis.Taken together,the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.
基金supported by the STI2030-Major Projects(2021ZD0200900 to Y.G.Y.)"Light of West China" Program of the Chinese Academy of Sciences(xbzg-zdsys-202302 to Y.G.Y.)
文摘The tree shrew(Tupaia belangeri)has long been proposed as a suitable alternative to non-human primates(NHPs)in biomedical and laboratory research due to its close evolutionary relationship with primates.In recent years,significant advances have facilitated tree shrew studies,including the determination of the tree shrew genome,genetic manipulation using spermatogonial stem cells,viral vector-mediated gene delivery,and mapping of the tree shrew brain atlas.However,the limited availability of tree shrews globally remains a substantial challenge in the field.Additionally,determining the key questions best answered using tree shrews constitutes another difficulty.Tree shrew models have historically been used to study hepatitis B virus(HBV)and hepatitis C virus(HCV)infection,myopia,and psychosocial stress-induced depression,with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases.Despite these efforts,the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research.This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model.We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies.The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models,meeting the increasing demands of life science and biomedical research.
基金This study was supported by the Planning Program of the Health Committee of Ganzhou(2022-1-5)the Key R&D Program of Jiangxi Province(20202BBGL73106)grants from the National Science Foundation of China(81771435).
文摘To the editor:Mood disorders(MD)are serious mental illnesses that commonly affect adolescents,leading to a high incidence of suicidal behaviour.1 In China,the suicide attempt(SA)rate for adolescents with MD is 51.96%,2 and over 500000 adolescent SA are reported annually in the USA due to depression.3 Risk factors for SA include gender,hormone levels,family conflict and,particularly,negative cognitive styles such as rumination.
基金the National Key Technology R&D Program(2015BA/13B01)Beijing National Science Foundation(7222236)+1 种基金Capital Health Research and Development of Special Fund(2022-1-4111)National Natural Science Foundation of China(82071528,82171529,82271569,82371530).
文摘Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder.However,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well understood.This reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood states.We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood state.We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects.Finally,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.
基金supported by the Ministry of Science and Tech-nology of the People's Republic of China(2021ZD0201900),Project 5(2021ZD0201905).
文摘Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.
基金supported by grants from National Natural Science Foundation of China (Grant Nos.81371990,81625015,81601945,and 81530070)the Program for Changjiang Scholars and Innovative Research Team in University (IRT_16R37)
文摘Increasing evidences show that aberrant subchondral bone remodeling plays an important role in the development of osteoarthritis(OA).However,how subchondral bone formation is activated and the mechanism by which increased subchondral bone turnover promotes cartilage degeneration during OA remains unclear.Here,we show that the mechanistic target of rapamycin complex 1(mTORC1)pathway is activated in subchondral bone preosteoblasts(Osterix+)from OA patients and mice.Constitutive activation of mTORC1 in preosteoblasts by deletion of the mTORC1 upstream inhibitor,tuberous sclerosis 1,induced aberrant subchondral bone formation,and sclerosis with little-to-no effects on articular cartilage integrity,but accelerated posttraumatic OA development in mice.In contrast,inhibition of mTORC1 in preosteoblasts by disruption of Raptor(mTORC1-specific component)reduced subchondral bone formation and cartilage degeneration,and attenuated post-traumatic OA in mice.Mechanistically,mTORC1 activation promoted preosteoblast expansion and Cxcl12 secretion,which induced subchondral bone remodeling and cartilage degeneration during OA.A Cxcl12-neutralizing antibody reduced cartilage degeneration and alleviated OA in mice.Altogether,these findings demonstrate that mTORC1 activation in subchondral preosteoblasts is not sufficient to induce OA,but can induce aberrant subchondral bone formation and secrete of Cxcl12 to accelerate disease progression following surgical destabilization of the joint.Pharmaceutical inhibition of the pathway presents a promising therapeutic approach for OA treatment.
文摘Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population. Aim To provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES. Methods An independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size. Results 56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as 'high quality' according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=-1.60,95% Cl -1.82 to -1.38,厂=67%) and all seven cognitive domains, with the SMD ranging from -0.87 to -1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=-1.90), Trail Making Test (TMT)(SMD=-1.36), Continuous Performance Test-Identical Pairs (SMD=-1.33), Hopkins Verbal Learning Test (SMD=-1.24), Brief Visuospatial Memory Test (SMD=-1.18), Mazes (SMD=-1.16), Category Fluency (SMD=-1.01), Spatial Span (SMD=-0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=-0.38). Conclusions Our meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.
基金supported by the National Natural Science Foundation of China,Nos.81925031(to YT),81820108026(to YT),81972967(to WJL),81872549(to YL)the Youth Program of National Natural Science Foundation of China,No.81801229(to YTX)+3 种基金a grant from Guangdong Science and Technology Department of China,Nos.2020B1212060018(to WJL),2020B1212030004(to WJL)the Natural Science Foundation of Guangdong Province,No.2019A1515011754(to WJL)the Science and Technology Program of Guangzhou of China,No.202007030001(to YT)the Science and Technology Planning Project of Guangzhou of China,No.201704030033(to YL).
文摘Radiation therapy is a standard treatment for head and neck tumors.However,patients often exhibit cognitive impairments following radiation therapy.Previous studies have revealed that hippocampal dysfunction,specifically abnormal hippocampal neurogenesis or neuroinflammation,plays a key role in radiation-induced cognitive impairment.However,the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly characterized.We found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/min.Furthermore,we observed a remarkable reduction in spike firing and excitatory synaptic input,as well as greatly enhanced inhibitory inputs,in hippocampal CA1 pyramidal neurons.Corresponding to the electrophysiological adaptation,we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of VGAT.Furthermore,in irradiated mice,long-term potentiation in the hippocampus was weakened and GluR1 expression was inhibited.These findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.
基金This study was supported by the National Natural Science Foundation of China(No.81630031)National Key Technology R&D Program(2015BAI13B01).
文摘There is an increasing heavy disease burden of major depressive disorder(MDD)globally.Both high diagnostic heterogeneity and complicated pathological mechanisms of MDD pose significant challenges.There is much evidence to support anhedonia as a core feature of MDD.In the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition,anhedonia is further emphasised as a key item in the diagnosis of major depression with melancholic features.Anhedonia is a multifaceted symptom that includes deficits in various aspects of reward processing,such as anticipatory anhedonia,consummatory anhedonia,and decision-making anhedonia.Anhedonia is expected to become an important clinicopathological sign for predicting the treatment outcome of MDD and assisting clinical decision making.However,the precise neurobiological mechanisms of anhedonia in MDD are not clearly understood.In this paper,we reviewed(1)the current understanding of the link between anhedonia and MDD;(2)the biological basis of the pathological mechanism of anhedonia in MDD;and(3)challenges in research on the pathological mechanisms of anhedonia in MDD.A more in-depth understanding of anhedonia associated with MDD will improve the diagnosis,prediction,and treatment of patients with MDD in the future.
基金supported in part by grants from the Ministry of Science and Technology to Yu-Kai Chang (NSC 102-2410-H-179-014-MY3)
文摘Purpose: The purpose of this study was to determine the effects of acute exercise on motor response inhibition using both behavioral and electrophysiological approaches. Methods: The P3 and N1 event-related potential (ERP) components were recorded while performing a stop-signal task in 21 college students following a moderately intense acute exercise bout for 30 min and a sedentary control session that involved reading. Results: Acute exercise induced a shorter stop signal response time (SSRT) as compared to control; however, the go response time (Go RT) remained unchanged. In examining the ERP data, acute exercise increased both P3 amplitude and latency but did not affect the N1 component. Conclusion: Acute exercise has a selective and beneficial effect on cognitive function, specifically affecting the motor response inhibition aspect of executive function. Furthermore, acute exercise predominately impacts later stages of information processing during motor response inhibition, which may lead to an increase in attentional resource allocation and confer the ability to successfully withhold a response to achieve motor response inhibition.
基金Lanzhou Science and Technology Project,No.2020-XG-71.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has caused major public panic in China.Pregnant women may be more vulnerable to stress,which may cause them to have psychological problems.AIM To explore the effects of perceived family support on psychological distress in pregnant women during the COVID-19 pandemic.METHODS A total of 2232 subjects were recruited from three cities in China.Through the online surveys,information on demographic data and health status during pregnancy were collected.Insomnia severity index,generalized anxiety disorder 7-item scale,patient health questionnaire-9,somatization subscale of the symptom check list 90 scale,and posttraumatic stress disorder checklist were used to assess the psychological distress.RESULTS A total of 1015(45.4%)women reported having at least one psychological distress.The women who reported having inadequate family support were more likely to suffer from multiple psychological distress(≥2 psychological distress)than women who received adequate family support.Among the women who reported less family support,41.8%reported depression,31.1%reported anxiety,8.2%reported insomnia,13.3%reported somatization and 8.9%reported posttraumatic stress disorder(PTSD),which were significantly higher than those who received strong family support.Perceived family support level was negatively correlated with depressive symptoms(r=-0.118,P<0.001),anxiety symptoms(r=-0.111,P<0.001),and PTSD symptoms(r=-0.155,P<0.001).CONCLUSION Family support plays an important part on pregnant women’s mental health during the COVID-19 pandemic.Better family support can help improve the mental health of pregnant women.
基金the National Natural Science Foundation of China,No. 30500158,30670708the Major Direc-tion Program of Chinese Academy of Sciences,No. KSCX2-YW-R-131+1 种基金the National Basic Research Project (973 Program) of China,No. 2007CB512306the Development Foundation of Institute of Psychology,Chinese Academy of Sci-ences,No. O9KF013001
文摘The traditional "brain-derived neurotrophic factor (BDNF) hypothesis of depression" proposes that impairment of the BDNF signaling pathway in the hippocampus and prefrontal cortex participates in the pathophysiology of depression, and antidepressants act by recovering/enhancing BDNF signal transduction. Recent studies have suggested that BDNF signaling pathways exert more diverse and complex effects on depression onset and antidepressant therapy than originally thought, which include: (1) inhibition of the BDNF-TrkB signaling pathway in the hippocampus and/or prefrontal cortex does not induce the depression-like behavioral phenotype, but significantly diminishes therapeutic effects, which suggests that the BDNF-TrkB signaling pathway lacks direct or key effects on occurrence of emotional disorders, whereas an intact and normal BDNF-TrkB signaling pathway is necessary for antidepressant therapy. (2) The BDNF-TrkB signaling pathway exhibits opposite regulatory effects on depressive behavior in the hippocampus-prefrontal cortex network and mesolimbic system, which suggests that BDNF regulates emotion by affecting the emotion-related neural network, but not a single brain region. (3) The BDNF-TrkB and proBDNF-p75Nm signaling pathways in the brain, respectively, enhance and suppress hippocampal neural plasticity, which demonstrated that different BDNF signaling pathways interact and restrict each other in the regulation of neural plasticity and emotional behaviors. (4) BDNF gene polymorphism might be associated with susceptibility to depression. These new findings extend our understanding of neuronal pathways and mechanisms of action of BDNF signaling and contribute to improved views to traditional "neurotrophic factor hypothesis of depression".
基金supported by the National Key R&D Program of China(2022YFC2010106)the Chinese Nutrition Society(CNS-NNSRG2021-61).
文摘With the largest ageing population in the world,China is faced with the huge chal-lenge of dementia.-However,previously reported estimates on the prevalence of dementia among Chinese older adults were inconsistent,varying from 2%to 13%.5°It is crucial for dementia prevention to determine the number of cases that could be delayed or prevented,but how to do this remains unclear.To address these research gaps,we aimed to provide population estimates of the prevalence of dementia in China and estimate the population attributable fractions(PAFs)of potentially modifiable risk factors.
基金the Ministry of Science and Technology China Brain Initiative Grant,No.2022ZD0204701the National Natural Science Foundation of China,Nos.82071386&81870982(all to JG)。
文摘Dendrites play irreplaceable roles in the nerve conduction pathway and are vulnerable to various insults.Peripheral axotomy of motor neurons results in the retraction of dendritic arbors,and the dendritic arbor can be re-expanded when reinnervation is allowed.RhoA is a target that regulates the cytoskeleton and promotes neuronal survival and axon regeneration.However,the role of RhoA in dendrite degeneration and regeneration is unknown.In this study,we explored the potential role of RhoA in dendrites.A line of motor neuronal conditional knockout mice was developed by crossbreeding HB9~(Cre+)mice with RhoA~(flox/flox)mice.We established two models for assaying dendrite degeneration and regeneration,in which the brachial plexus was transection or crush injured,respectively.We found that at 28 days after brachial plexus transection,the density,complexity,and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice were slightly decreased compared with that in Cre mice.Dendrites underwent degeneration at 7 and 14 days after brachial plexus transection and recovered at 28–56 days.The density,complexity,and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice recovered compared with results in Cre mice.These findings suggest that RhoA knockout in motor neurons attenuates dendrite degeneration and promotes dendrite regeneration after peripheral nerve injury.
基金supported by the National Natural Science Foundation of China,Nos.82071386 (to JS),81870982 (to JS)&81571182 (to JS)the National Key Basic Research Program of China,No.2014CB542202 (to JS)+3 种基金the Program for Changjiang Scholars and Innovative Research Team in University of China,No.IRT-16R37 (to JS)Key Research&Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory of China,No.2018GZR110104008 (to HZ)Research Grant of Guangdong Province Key Laboratory of Psychiatric Disorders of China,No.N201904 (to JS)Natural Science Foundation of Guangdong Province of China,No.2017A030312009 (to JS)。
文摘Wallerian degeneration,the progressive disintegration of distal axons and myelin that occurs after peripheral nerve injury,is essential for creating a permissive microenvironment for nerve regeneration,and involves cytoskeletal reconstruction.However,it is unclear whether microtubule dynamics play a role in this process.To address this,we treated cultured sciatic nerve explants,an in vitro model of Wallerian degeneration,with the microtubule-targeting agents paclitaxel and nocodazole.We found that paclitaxel-induced microtubule stabilization promoted axon and myelin degeneration and Schwann cell dedifferentiation,whereas nocodazole-induced microtubule destabilization inhibited these processes.Evaluation of an in vivo model of peripheral nerve injury showed that treatment with paclitaxel or nocodazole accelerated or attenuated axonal regeneration,as well as functional recovery of nerve conduction and target muscle and motor behavior,respectively.These results suggest that microtubule dynamics participate in peripheral nerve regeneration after injury by affecting Wallerian degeneration.This study was approved by the Animal Care and Use Committee of Southern Medical University,China(approval No.SMUL2015081) on October 15,2015.