NBEA(MIM#604,889)is a novel disease causative gene that responds for neurodevelopment disorder with or without generalized epilepsy(NEDEGE,MIM#619,157).It encodes neurobeachin protein,a multi-domain neuro-specific sca...NBEA(MIM#604,889)is a novel disease causative gene that responds for neurodevelopment disorder with or without generalized epilepsy(NEDEGE,MIM#619,157).It encodes neurobeachin protein,a multi-domain neuro-specific scaf-folding protein that plays a vital role in vesicle trafficking and synaptic structure.NBEA was initially observed in an idiopathic autism patient,and thus NBEA has been regarded as a candidate autism gene for nearly two decades[1-4].In 2018,Mulhern et al.reported 24 individuals with de novo heterozygous NBEA variants with neurodevelopmental delay with autism and early onset generalized epilepsy,which led the Online Mendian Inheritance in Man(OMIM)team to identify it as a disease-causing gene for NEDEGE[5].Since then,only a few NBEA-related cases with similar clinical phenotypes have been reported[6-8].展开更多
Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psych...Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psychiatric,and behavioral issues,highlighting the urgent need for autism-competent healthcare providers in general healthcare.This review aims to equip primary care providers(PCPs)with a concise summary of common CCs and strategies for effective identification.A panel of experts with extensive experience in caring for autistic children collaboratively summarized key literature,research evidence,and existing clinical trial outcomes,supplementing their clinical expertise.Autistic children consistently show higher rates of both medical and mental health issues.Despite greater healthcare utilization,many autistic individuals report unmet needs.CCs can impair behavior,functioning,and well-being,but are often treatable when recognized early.Timely identification and management of medical and psychiatric CCs are critical for improving outcomes for autistic children and their families.This evidence-based review supports PCPs in enhancing their knowledge,fostering early recognition,and delivering comprehensive,responsive care.展开更多
Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal funct...Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.展开更多
Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabo...Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabolism.In the context of galactose metabolism,intracellular glucose levels are heightened.Galactose mutarotase(GALM)plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion ofβ-D-galactose intoα-D-galactose(α-D-G).The latter is then converted into glucose-6-phosphate,improving glucose metabolism levels.However,the involvement of GALM in AD progression is still unclear.In the present study,we found that the expression of GALM was significantly increased in AD patients and model mice.Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein(APP)and APP-cleaving enzymes including a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),and presenilin-1(PS1).Interestingly,genetic overexpression of GALM reduced APP and Aβdeposition by increasing the maturation of ADAM10,although it did not alter the expression of BACE1 and PS1.Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation(LTP)and spatial learning and memory in AD model mice.Importantly,directα-D-G(20 mg/kg,i.p.)also inhibited Aβdeposition by increasing the maturation of ADAM10,thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice.Taken together,our results indicate that GALM shifts APP processing towardsα-cleavage,preventing Aβgeneration by increasing the level of mature ADAM10.These findings indicate that GALM may be a potential therapeutic target for AD,andα-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.展开更多
BACKGROUND Childhood trauma and parental socialization have been postulated as environmental factors of at-risk mental state(ARMS).Parental socialization is the process through which parents shape children’s self-reg...BACKGROUND Childhood trauma and parental socialization have been postulated as environmental factors of at-risk mental state(ARMS).Parental socialization is the process through which parents shape children’s self-regulation by providing guidance and protection.Although the impact of trauma on ARMS has been theorized,its clinical implications have not yet been fully clarified in adolescence,nor have explanatory models of parenting styles been established.AIM To investigate the role of traumatic experiences in the appearance of ARMS in the general adolescent population,considering the influence of parental socialization.METHODS A cross-sectional study of 697 adolescents aged 11-15 years was conducted,during which several questionnaires assessing childhood trauma,psychotic symptoms,and parenting styles were administered.The sample was divided into control,low-risk,medium-risk,and high-risk groups.RESULTS Some 2.8%(n=19)of the adolescents presented ARMS and the presence of childhood trauma was associated with an increased risk of ARMS.Furthermore,the presence of abuse was greater in the high-risk and low-risk groups compared to controls.Regarding parental socialization,it was determined that a family socialization style based on greater affection–communication decreased the probability of ARMS.Finally,using PROCESS model 1(regressionbased path analysis that uses ordinary least squares regression),results suggested that low levels of affection and communication may mediate the relationship between childhood trauma and ARMS in adolescents.CONCLUSION These results highlight the importance of the early detection of trauma in preventing ARMS,without forgetting the importance of socialization styles.展开更多
儿童神经遗传罕见病多起病早,缺乏特异性治疗手段,病死率高,严重危及患儿的健康及生命。以腺相关病毒(adeno-associated virus,AAV)介导的基因治疗为代表的疾病修正治疗为儿童神经遗传罕见病的治疗提供了新的方向。目前,AAV介导的基因...儿童神经遗传罕见病多起病早,缺乏特异性治疗手段,病死率高,严重危及患儿的健康及生命。以腺相关病毒(adeno-associated virus,AAV)介导的基因治疗为代表的疾病修正治疗为儿童神经遗传罕见病的治疗提供了新的方向。目前,AAV介导的基因治疗在儿童神经遗传罕见病治疗中有了突破性的进展,已有针对脊髓性肌萎缩症、芳香族L-氨基酸脱羧酶缺乏症、杜氏肌营养不良症的基因治疗药物获得美国食品药品管理局(Food and Drug Administration,FDA)/欧洲药品管理局(European Medicines Association,EMA)批准上市。多项临床前以及临床试验研究数据显示AAV介导的基因治疗在儿童神经遗传罕见病中有良好的应用前景,针对罕见病药物启动快速审批流程,这为神经遗传罕见病患儿的治疗带来了希望。但AAV介导的基因治疗属于新兴技术,存在着一定的风险和挑战,需要建立规范的监管体系以及健全的长期随访制度,以评估基因治疗的有效性及安全性。展开更多
Antenatal administration of magnesium sulfate is an important part of the neuroprotective strategy for preterm infants. Strong evidence from five randomized controlled trials and five meta-analyses has demonstrated th...Antenatal administration of magnesium sulfate is an important part of the neuroprotective strategy for preterm infants. Strong evidence from five randomized controlled trials and five meta-analyses has demonstrated that magnesium sulfate, when administered before preterm delivery, significantly reduces the risk of cerebral palsy at two years. Through secondary analyses of randomized controlled trials and other original clinical studies, this state-of-the-art review highlights the absence of serious adverse effects in both pregnant women and neonates, as well as the impact of maternal body mass index and preeclamptic status on the maternal and neonatal magnesium levels, which could influence the magnitude of the neuroprotective effect. Although antenatal magnesium sulfate is a cost-effective strategy, some practice surveys have demonstrated that the use of magnesium sulfate is not sufficient and that its use is heterogeneous, differing among different maternity wards. Since 2010, an increasing number of obstetrical societies have recommended its use to improve the neurological outcomes of preterm infants, especially the International Federation of Gynecology and Obstetrics and World Health Organization in 2015, and France in 2017. Considering the neuroprotective impact of magnesium sulfate when administered before delivery, postnatal administration should be considered, and its effects should be assessed using randomized controlled trials.展开更多
Attention deficit hyperactivity disorder(ADHD) is the most common neurodevelopmental disorder in children and adolescents, with prevalence ranging between 5% and 12% in the developed countries. Tic disorders(TD) are c...Attention deficit hyperactivity disorder(ADHD) is the most common neurodevelopmental disorder in children and adolescents, with prevalence ranging between 5% and 12% in the developed countries. Tic disorders(TD) are common co-morbidities in paediatric ADHD patients with or without pharmacotherapy treatment. There has been conflicting evidence of the role of psychostimulants in either precipitating or exacerbating TDs in ADHD patients. We carried out a literature review relating to the management of TDs in children and adolescents with ADHD through a comprehensive search of MEDLINE, EMBASE, CINAHL and Cochrane databases. No quantitative synthesis(meta-analysis) was deemed appropriate. Metaanalysis of controlled trials does not support an association between new onset or worsening of tics and normal doses of psychostimulant use. Supratherapeutic doses of dextroamphetamine have been shown to exacerbate TD. Most tics are mild or moderate and respond to psychoeducation and behavioural management. Level A evidence support the use of alpha adrenergic agonists, including Clonidine and Guanfacine, reuptake noradrenenaline inhibitors(Atomoxetine) and stimulants(Methylphenidate and Dexamphetamines) for the treatment of Tics and comorbid ADHD. Priority should be given to the management of co-morbid Tourette's syndrome(TS) or severely disabling tics in children and adolescents with ADHD. Severe TDs may require antipsychotic treatment. Antipsychotics, especially Aripiprazole, are safe and effective treatment for TS or severe Tics, but they only moderately control the co-occurring ADHD symptomatology. Short vignettes of different common clinical scenarios are presented to help clinicians determine the most appropriate treatment to consider in each patient presenting with ADHD and co-morbid TDs.展开更多
BACKGROUND Sustaining the mental health of autistic children’s parents can be demanding.AIM To determine the effect of remote support courses on the mental health of parents and the development of autistic children.M...BACKGROUND Sustaining the mental health of autistic children’s parents can be demanding.AIM To determine the effect of remote support courses on the mental health of parents and the development of autistic children.METHODS Parents of 140 autistic children were randomly assigned to two groups receiving a 2-week intervention:The control group received caregiver-mediated intervention(CMI);the experimental group received CMI with remote family psychological support courses(R-FPSC).The Parenting Stress Index-Short Form,Parenting Sense of Competence Scale,Generalized Anxiety Disorder-7,and Patient Health Questionnaire-9 were used to measure parents’mental health.The Childhood Autism Rating Scale and Gesell Developmental Schedules were used to evaluate children’s development.RESULTS Improved parenting stress,sense of competence,depression,and anxiety were found in both groups,but improvements in parenting stress(81.10±19.76 vs 92.10±19.26,P<0.01)and sense of competence(68.83±11.23 vs 63.91±10.86,P<0.01)were greater in the experimental group,although the experimental group showed no significant reduction in depression or anxiety.Children’s development did not differ significantly between the groups at follow-up;however,experimental group parents exhibited a short-term increase in training enthusiasm(12.78±3.16 vs 11.57±3.15,P<0.05).CONCLUSION Integrating R-FPSC with CMI may be effective in reducing parenting stress,enhancing parents’sense of competence,and increasing parents'training enthusiasm.展开更多
The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease...The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.展开更多
基金study was funded in part by the National Natural Science Foundation of China(Grant no.81771409 and 82071462)Natural Science Foundation of Hunan Province(Grant no.2021JJ40969).
文摘NBEA(MIM#604,889)is a novel disease causative gene that responds for neurodevelopment disorder with or without generalized epilepsy(NEDEGE,MIM#619,157).It encodes neurobeachin protein,a multi-domain neuro-specific scaf-folding protein that plays a vital role in vesicle trafficking and synaptic structure.NBEA was initially observed in an idiopathic autism patient,and thus NBEA has been regarded as a candidate autism gene for nearly two decades[1-4].In 2018,Mulhern et al.reported 24 individuals with de novo heterozygous NBEA variants with neurodevelopmental delay with autism and early onset generalized epilepsy,which led the Online Mendian Inheritance in Man(OMIM)team to identify it as a disease-causing gene for NEDEGE[5].Since then,only a few NBEA-related cases with similar clinical phenotypes have been reported[6-8].
文摘Autism is a heterogeneous condition with a rising prevalence and demand for specialized care.Autistic children are more likely than neurotypical peers to experience co-occurring conditions(CCs),including medical,psychiatric,and behavioral issues,highlighting the urgent need for autism-competent healthcare providers in general healthcare.This review aims to equip primary care providers(PCPs)with a concise summary of common CCs and strategies for effective identification.A panel of experts with extensive experience in caring for autistic children collaboratively summarized key literature,research evidence,and existing clinical trial outcomes,supplementing their clinical expertise.Autistic children consistently show higher rates of both medical and mental health issues.Despite greater healthcare utilization,many autistic individuals report unmet needs.CCs can impair behavior,functioning,and well-being,but are often treatable when recognized early.Timely identification and management of medical and psychiatric CCs are critical for improving outcomes for autistic children and their families.This evidence-based review supports PCPs in enhancing their knowledge,fostering early recognition,and delivering comprehensive,responsive care.
基金supported by the National Natural Science Foundation of China,No.82201582(to QT)Scientific and Technological Research Program of Chongqing Municipal Education Commission,No.KJQN202200457(to QT)+3 种基金General Project of Changqing Natural Science Foundation,No.cstc2021jcyjmsxmX0442(to ZL)CQMU Program for Youth Innovation in Future Medicine,No.W0044(to ZD and GH)Direct Research Project for PhD of Chongqing,No.CSTB2022BSXM-JCX0051(to ZL)the Project of the Top-Notch Talent Cultivation Program For the Graduate Students of Chongqing Medical University,No.BJRC202310(to CG)。
文摘Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.
基金supported by grants from the National Natural Science Foundation of China(32371030,82371194,and 82071395)the Natural Science Foundation of Chongqing(CSTB2022NSCQ-LZX0010 and CSTB2024NSCQ-MSX0269)the CQMU Program for Youth Innovation in Future Medicine(W0044).
文摘Alzheimer’s disease(AD)is the most prevalent neurodegenerative disorder worldwide,causing dementia and affecting millions of individuals.One prominent characteristic in the brains of AD patients is glucose hypometabolism.In the context of galactose metabolism,intracellular glucose levels are heightened.Galactose mutarotase(GALM)plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion ofβ-D-galactose intoα-D-galactose(α-D-G).The latter is then converted into glucose-6-phosphate,improving glucose metabolism levels.However,the involvement of GALM in AD progression is still unclear.In the present study,we found that the expression of GALM was significantly increased in AD patients and model mice.Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein(APP)and APP-cleaving enzymes including a disintegrin and metalloprotease 10(ADAM10),β-site APP-cleaving enzyme 1(BACE1),and presenilin-1(PS1).Interestingly,genetic overexpression of GALM reduced APP and Aβdeposition by increasing the maturation of ADAM10,although it did not alter the expression of BACE1 and PS1.Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation(LTP)and spatial learning and memory in AD model mice.Importantly,directα-D-G(20 mg/kg,i.p.)also inhibited Aβdeposition by increasing the maturation of ADAM10,thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice.Taken together,our results indicate that GALM shifts APP processing towardsα-cleavage,preventing Aβgeneration by increasing the level of mature ADAM10.These findings indicate that GALM may be a potential therapeutic target for AD,andα-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
基金Supported by Universidad Cardenal Herrera-CEU,CEU Universities,No.GIR24/27。
文摘BACKGROUND Childhood trauma and parental socialization have been postulated as environmental factors of at-risk mental state(ARMS).Parental socialization is the process through which parents shape children’s self-regulation by providing guidance and protection.Although the impact of trauma on ARMS has been theorized,its clinical implications have not yet been fully clarified in adolescence,nor have explanatory models of parenting styles been established.AIM To investigate the role of traumatic experiences in the appearance of ARMS in the general adolescent population,considering the influence of parental socialization.METHODS A cross-sectional study of 697 adolescents aged 11-15 years was conducted,during which several questionnaires assessing childhood trauma,psychotic symptoms,and parenting styles were administered.The sample was divided into control,low-risk,medium-risk,and high-risk groups.RESULTS Some 2.8%(n=19)of the adolescents presented ARMS and the presence of childhood trauma was associated with an increased risk of ARMS.Furthermore,the presence of abuse was greater in the high-risk and low-risk groups compared to controls.Regarding parental socialization,it was determined that a family socialization style based on greater affection–communication decreased the probability of ARMS.Finally,using PROCESS model 1(regressionbased path analysis that uses ordinary least squares regression),results suggested that low levels of affection and communication may mediate the relationship between childhood trauma and ARMS in adolescents.CONCLUSION These results highlight the importance of the early detection of trauma in preventing ARMS,without forgetting the importance of socialization styles.
文摘儿童神经遗传罕见病多起病早,缺乏特异性治疗手段,病死率高,严重危及患儿的健康及生命。以腺相关病毒(adeno-associated virus,AAV)介导的基因治疗为代表的疾病修正治疗为儿童神经遗传罕见病的治疗提供了新的方向。目前,AAV介导的基因治疗在儿童神经遗传罕见病治疗中有了突破性的进展,已有针对脊髓性肌萎缩症、芳香族L-氨基酸脱羧酶缺乏症、杜氏肌营养不良症的基因治疗药物获得美国食品药品管理局(Food and Drug Administration,FDA)/欧洲药品管理局(European Medicines Association,EMA)批准上市。多项临床前以及临床试验研究数据显示AAV介导的基因治疗在儿童神经遗传罕见病中有良好的应用前景,针对罕见病药物启动快速审批流程,这为神经遗传罕见病患儿的治疗带来了希望。但AAV介导的基因治疗属于新兴技术,存在着一定的风险和挑战,需要建立规范的监管体系以及健全的长期随访制度,以评估基因治疗的有效性及安全性。
文摘Antenatal administration of magnesium sulfate is an important part of the neuroprotective strategy for preterm infants. Strong evidence from five randomized controlled trials and five meta-analyses has demonstrated that magnesium sulfate, when administered before preterm delivery, significantly reduces the risk of cerebral palsy at two years. Through secondary analyses of randomized controlled trials and other original clinical studies, this state-of-the-art review highlights the absence of serious adverse effects in both pregnant women and neonates, as well as the impact of maternal body mass index and preeclamptic status on the maternal and neonatal magnesium levels, which could influence the magnitude of the neuroprotective effect. Although antenatal magnesium sulfate is a cost-effective strategy, some practice surveys have demonstrated that the use of magnesium sulfate is not sufficient and that its use is heterogeneous, differing among different maternity wards. Since 2010, an increasing number of obstetrical societies have recommended its use to improve the neurological outcomes of preterm infants, especially the International Federation of Gynecology and Obstetrics and World Health Organization in 2015, and France in 2017. Considering the neuroprotective impact of magnesium sulfate when administered before delivery, postnatal administration should be considered, and its effects should be assessed using randomized controlled trials.
文摘Attention deficit hyperactivity disorder(ADHD) is the most common neurodevelopmental disorder in children and adolescents, with prevalence ranging between 5% and 12% in the developed countries. Tic disorders(TD) are common co-morbidities in paediatric ADHD patients with or without pharmacotherapy treatment. There has been conflicting evidence of the role of psychostimulants in either precipitating or exacerbating TDs in ADHD patients. We carried out a literature review relating to the management of TDs in children and adolescents with ADHD through a comprehensive search of MEDLINE, EMBASE, CINAHL and Cochrane databases. No quantitative synthesis(meta-analysis) was deemed appropriate. Metaanalysis of controlled trials does not support an association between new onset or worsening of tics and normal doses of psychostimulant use. Supratherapeutic doses of dextroamphetamine have been shown to exacerbate TD. Most tics are mild or moderate and respond to psychoeducation and behavioural management. Level A evidence support the use of alpha adrenergic agonists, including Clonidine and Guanfacine, reuptake noradrenenaline inhibitors(Atomoxetine) and stimulants(Methylphenidate and Dexamphetamines) for the treatment of Tics and comorbid ADHD. Priority should be given to the management of co-morbid Tourette's syndrome(TS) or severely disabling tics in children and adolescents with ADHD. Severe TDs may require antipsychotic treatment. Antipsychotics, especially Aripiprazole, are safe and effective treatment for TS or severe Tics, but they only moderately control the co-occurring ADHD symptomatology. Short vignettes of different common clinical scenarios are presented to help clinicians determine the most appropriate treatment to consider in each patient presenting with ADHD and co-morbid TDs.
基金Supported by The National Key R and D Program of China,No.2023YFC3604805The Key Scientific and Technological Projects of Guangdong Province,No.2018B030335001Guangzhou Science and Technology Program,No.202007030002.
文摘BACKGROUND Sustaining the mental health of autistic children’s parents can be demanding.AIM To determine the effect of remote support courses on the mental health of parents and the development of autistic children.METHODS Parents of 140 autistic children were randomly assigned to two groups receiving a 2-week intervention:The control group received caregiver-mediated intervention(CMI);the experimental group received CMI with remote family psychological support courses(R-FPSC).The Parenting Stress Index-Short Form,Parenting Sense of Competence Scale,Generalized Anxiety Disorder-7,and Patient Health Questionnaire-9 were used to measure parents’mental health.The Childhood Autism Rating Scale and Gesell Developmental Schedules were used to evaluate children’s development.RESULTS Improved parenting stress,sense of competence,depression,and anxiety were found in both groups,but improvements in parenting stress(81.10±19.76 vs 92.10±19.26,P<0.01)and sense of competence(68.83±11.23 vs 63.91±10.86,P<0.01)were greater in the experimental group,although the experimental group showed no significant reduction in depression or anxiety.Children’s development did not differ significantly between the groups at follow-up;however,experimental group parents exhibited a short-term increase in training enthusiasm(12.78±3.16 vs 11.57±3.15,P<0.05).CONCLUSION Integrating R-FPSC with CMI may be effective in reducing parenting stress,enhancing parents’sense of competence,and increasing parents'training enthusiasm.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82071395)the Natural Science Foundation of Chongqing(Grant Nos.cstc2021ycjh-bgzxm0186,cstc2020jcyj-zdxmX0004,and cstc2021jcyj-bsh0023)the CQMU Program for Youth Innovation in Future Medicine(Grant No.W0044).
文摘The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.
