Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical imp...Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical improvement as measured by evolution scales. Objectives: The present study sought to explore expectations and level of satisfaction in patients after DBS surgery with a semi-structured questionnaire and subsequent correlation with functional scales, Quality of Life (QoL), and motor and non-motor symptoms. Methods: We performed descriptive statistics to represent demographic data, Wilcoxon rank tests to determine significant differences, and Spearman correlation between the applied scales. Results: We evaluated 20 patients with a history of DBS surgery. 45% were female, with a mean age of 55.7 ± 14.15 years, a mean disease duration of 13.42 ± 8.3 years, and a mean time after surgery of 3.18 ± 1.86 years. Patients reported surgery meeting expectations in 85.5% and continued satisfaction in 92%. These two variables showed a significant correlation. Conclusions: This sample of patients remained satisfied after DBS surgery, although we found no differences in motor and non-motor clinimetric scales. Further studies are needed to confirm the importance of assessing quality of life in patients with DBS.展开更多
Introduction: Complications of Urinary sphincter disorders of neurological origin can be life threatening. The objective of this study was to describe the prognosis of urinary sphincter disorders during neurological c...Introduction: Complications of Urinary sphincter disorders of neurological origin can be life threatening. The objective of this study was to describe the prognosis of urinary sphincter disorders during neurological conditions. Methods: This was a six-month analytical study conducted at the neurological unit of the Hôpital national Ignace Deen. Including patients with urinary sphincter disorders following a neurological condition;Chi-square, Fischer, and Student’s t-tests were used for variables with a p value less than 0.10 and then included in a logistic model with a significance level set at 0.05 and a 95% confidence interval. Results: We collected 1081 patients among whom, 324 presented, that is to say a frequency of 30%, which concerned subjects aged 57.3 ± 16.4 years with a slight female predominance 50.3%. Urinary incontinence (80.6%) was associated with complications such as urinary tract infection with a high proportion of cerebral damage (92.3%). HIV infection (P = 0.015), bedsores (P = 0.049), and inhalation pneumonia (P = 0.001) were the main poor prognostic factors. Conclusion: Urinary sphincter disorders are elements of poor prognosis, both vital and functional, concerning elderly subjects with a predominance of urinary incontinence. HIV infection, bedsores, pneumopathy are poor prognostic factors.展开更多
Intraventricular haemorrhage (IVH) is an extremely rare and poorly described complication of central nervous system Tuberculosis (CNS-TB). In this study, we report the case of a 42-year-old man who presented with a we...Intraventricular haemorrhage (IVH) is an extremely rare and poorly described complication of central nervous system Tuberculosis (CNS-TB). In this study, we report the case of a 42-year-old man who presented with a weakness of the left hemibody with diffuse headache, altered consciousness associated with fever. No notion of contagion was noted. Brain computed tomography (CT) showed a hematoma in the occipital horns of the lateral ventricles with peri-lesional oedema of the right hemisphere;after injection of contrast product (CP), there were ring-shaped contrasts in the occipital horn of the lateral ventricle and the right thalamus. Angioscan showed no aneurysms or vascular anomalies. Chest X-ray showed micronodular opacities less than 1.5 cm in size in relation to miliary. Xpert MTB/RIF of sputum and cerebrospinal fluid (CSF) showed Mycobacterium tuberculosis (MT). The patient’s course was favourable under antihypertensive and antitubercular treatment. Conclusion: This case illustrates the diagnostic difficulties of CNS-TB due to the polymorphism of the clinical and radiological presentation of CNS-TB.展开更多
Approximately 20% of patients with sleep apnea will have headaches and 25% of patients with other sleep disorders will also experience headaches. We aim to evaluate sleep apnea related symptom prevalence in patient wi...Approximately 20% of patients with sleep apnea will have headaches and 25% of patients with other sleep disorders will also experience headaches. We aim to evaluate sleep apnea related symptom prevalence in patient with headache presenting to neurology outpatient clinics. Twenty four patients with headache were asked for sleep apnea symptoms. The prevalence of snoring, excessive daytime sleepiness and witnessed apnea was 33.3%, 20.8% and 4.2%, respectively. Among sleep apnea symptoms, the presence of at least one symptom, at least two symptoms and all three symptoms were 9 (37.5%), 4 (16.7%) and 1 (4.2%), respectively. The frequency of major symptoms of sleep apnea syndrome was high in patient with nonspecific headache. In the light of literature review, in case of a suspicion of sleep disorder in a headache patient, it would be appropriate to question the major symptoms of OSAS, and to refer the patient to a polysomnographic evaluation for an objective diagnosis. This approach would be helpful to improve the quality of life of patients with headache.展开更多
Meta-analyses are often misused and underused in neurology. This editorial provides some comments on the role of meta-analyses in neurological research.Recently, a huge increase in the number of metaanalyses and syste...Meta-analyses are often misused and underused in neurology. This editorial provides some comments on the role of meta-analyses in neurological research.Recently, a huge increase in the number of metaanalyses and systematic reviews has been observed in neurological journals. The major strengths of metaanalyses are the increase of statistical power. However, as for any other investigative tool, meta-analytic research is a research method itself which can produce severe shortcomings. Specifically, the issues of search terms, time periods of published studies, databases used for searching, the definitions of inclusion and exclusion criteria for papers(which greatly affect clinical heterogeneity), publication bias; and the statistical methods used, dramatically influence the results of metaanalyses. The main problem of meta-analyses is that they cannot be expected to overcome the limitations of the studies they include(the so-called "garbage in,garbage out" phenomenon). Furthermore, most systematic reviews in the neurological literature lead to the unsatisfying and clinically frustrating statement "further studies are needed". However it is much more frustrating to see how the gaps in scientific knowledge identified by meta-analyses have not been translated into serious efforts to fill them. Besides their role in evaluating efficacy and tolerability of drugs, meta-analyses may be used to assess diagnostic values of debatable clinical findings, as they represent powerful tools to try to answer questions not posed by individual studies and to settle controversies arising from conflicting claims.展开更多
The"Chinese Society of Neurology,Basic and Clinical Psychiatry Branch's 15tvh Academic Conference",hosted by the Chinese Society of Neurology,Basic and Clinical Psychiatry Branch and cohosted by the Shan...The"Chinese Society of Neurology,Basic and Clinical Psychiatry Branch's 15tvh Academic Conference",hosted by the Chinese Society of Neurology,Basic and Clinical Psychiatry Branch and cohosted by the Shanghai Mental Health Center Affiliated to Shanghai Jiaotong University School of Medicine and the Psychology Department of the展开更多
Long QT syndrome(LQTS) is a cardiac conduction disorder that predisposes patients at potentially fatal cardiac events. Inherited conditions and acquired factors contribute to LQTS. A number of frequently prescribed CN...Long QT syndrome(LQTS) is a cardiac conduction disorder that predisposes patients at potentially fatal cardiac events. Inherited conditions and acquired factors contribute to LQTS. A number of frequently prescribed CNS-active drugs prolong the QT interval. The clinical neurologist may encounter LQTS when initiating a pharmacotherapy or when increasing the dosage of drugs. The clinical neurologist may also encounter LQTS during the diagnostic work-up of patients with unexplained loss of consciousness, because LQTS may present as convulsive syncope. Some studies report an association of LQTS and stroke. Awareness of LQTS may help to recognize and prevent potentially fatal cardiac events associated with LQTS. This concise article highlights the clinically most relevant aspects of LQTS in the field of neurology.展开更多
Background: According to the World Health Organization, about 5% of children world-wide of 14-year-old and under have a moderate to severe developmental disability, and up to 15% of children under 5-year-old are devel...Background: According to the World Health Organization, about 5% of children world-wide of 14-year-old and under have a moderate to severe developmental disability, and up to 15% of children under 5-year-old are developmentally delayed. Purpose: To determine the prevalence, socio-demographic profile, aetiologies, and the clinical presentation of developmental delay in children less than 6-year-old at the child neurology unit in a university-affiliated hospital in Yaounde. Materials and methods: It was a crosssectional descriptive study carried out in Yaounde Gynaeco-Obstetric and Paediatric Hospital (Cameroon) from August to December 2012. Children aged between 5 - 72 months with a developmental quotient less than 70 were enrolled. Developmental delay (DD) was diagnosed and classified using the Denver developmental screening test (DDST). Data concerning the child (age, gender, severity of DD), the mother (age, age at conception, educational level, marital status), history of pregnancy and delivery, perinatal and postnatal events, results of para-clinical explorations (EEG, CT-scan, genetic tests), the severity of DD and the probable or demonstrate cause of DD were recorded on a standardized questionnaire. The chisquare test was used to compare variables. Results: During the study period, 2171 children aged 5 - 72 months consulted the paediatric department of the hospital, 296 were examined at the child neurology unit of which 153 had a developmental quotient less than 70, giving a hospital prevalence of 7.0% and a prevalence of 51.7% at the child neurology unit. The mean age was 26.6 ± 18.0 months and there were 56% males. The main reason for consulting was tonus disorder (43.8%) and the developmental area of parental concern was the motor domain (90.2%). Regarding the clinical presentation, 75.2% of our population were children with cerebral palsy. DD was severe, mild, moderate and profound respectively in 14.2%, 13.5%, 12.2%, and 11.1%. Gross DD represented 90.2% of all DD children. The causes of DD were hypoxic-ischemic encephalopathy (41.8%), epilepsy (13.7%), sequelae of meningitis (6.5%), sequelae of kernicterus (6.5%), and infectious embryofoetopathies (5.2%). Conclusion: Developmental delay is frequent in paediatric neurology, with perinatal disorders being the leading aetiologies in Cameroon. Prevention of perinatal hypoxic-ischemic encephalopathy risk factors needs to be reinforced.展开更多
Background: Although patients with acute headache frequently present in emergency department, the causes and predictors of short-term outcome in patients with acute headache in general neurology have not been adequate...Background: Although patients with acute headache frequently present in emergency department, the causes and predictors of short-term outcome in patients with acute headache in general neurology have not been adequately investigated. Methods: We prospectively reviewed the medical records of 130 hospitalized acute headache pa-tients in general neurology of China. Their initial CT scan was assessed, as was their lumbar puncture (LP) examination if performed. Results: The main cause of acute headache was acute secondary headache (80.8%), which was mainly attributable to acute cerebrovascular events (72.4%) followed by intracranial infection (19.0%). Among the 10.8% of patients who died during hospitalization most (85.7%) had subarachnoid hemorrhage (SAH). Significant predictors of survival were severe headache versus thunderclap headache, meningismus, de-layed loss of consciousness, and hypertension (all p < 0.05). Multiple logistic regression analyses showed significant differences in severe headache or thunderclap headache (OR, 0.255;95%CI, 0.066 - 0.990;p = 0.048) and delayed loss of consciousness (OR, 0.060;95%CI, 0.016 - 0.224, p = 0.000) between patients who died and those who survived. Conclusions: The main underlying cause of hospitalized acute headache was acute cerebrovascular events. Severe headache and delayed loss of consciousness are predictors for poor outcome of acute headache.展开更多
A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in...A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.展开更多
Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport ...Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.展开更多
Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exoso...Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.展开更多
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen...Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.展开更多
Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus...Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.展开更多
Parkinson’s disease(PD,OMIM#168600)is a common neurodegenerative disorder with a global prevalence of approximately 8.5 million.PD is characterized by four cardinal motor symptoms:bradykinesia,rigidity,resting tremor...Parkinson’s disease(PD,OMIM#168600)is a common neurodegenerative disorder with a global prevalence of approximately 8.5 million.PD is characterized by four cardinal motor symptoms:bradykinesia,rigidity,resting tremor,and subsequently by postural instability.It usually involves non-motor symptoms such as rapid eye movement sleep disorder,dementia,anosmia,and autonomic dysfunction.The gene glucocerebrosidase 1(GBA1),which encodes the lysosomal enzyme glucocerebrosidase(GCase)(IUBMB:EC 3.2.1.45),shows strong linkage with PD;variants of GBA1 are the commonest genetic association with PD(Sidransky et al.,2009).Several mechanisms may underlie the relationship between GBA1 mutations/variants and the molecular pathology of PD(Figure 1A and B).展开更多
BACKGROUND In recent years,the prevalence of obesity and metabolic syndrome in type 1 diabetes(T1DM)patients has gradually increased.Insulin resistance in T1DM deserves attention.It is necessary to clarify the relatio...BACKGROUND In recent years,the prevalence of obesity and metabolic syndrome in type 1 diabetes(T1DM)patients has gradually increased.Insulin resistance in T1DM deserves attention.It is necessary to clarify the relationship between body composition,metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention.AIM To assess body composition(BC)in T1DM patients and evaluate the relationship between BC,metabolic syndrome(MS),and insulin resistance in these indi-viduals.METHODS A total of 101 subjects with T1DM,aged 10 years or older,and with a disease duration of over 1 year were included.Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters.Clinical and laboratory data were collected,and insulin resistance was calculated using the estimated glucose disposal rate(eGDR).RESULTS MS was diagnosed in 16/101 patients(15.84%),overweight in 16/101 patients(15.84%),obesity in 4/101(3.96%),hypertension in 34/101(33.66%%)and dyslip-idemia in 16/101 patients(15.84%).Visceral fat index(VFI)and trunk fat mass were significantly and negatively correlated with eGDR(both P<0.001).Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients.Binary logistic regression analysis revealed that significant factors for MS included eGDR[P=0.017,odds ratio(OR)=0.109],VFI(P=0.030,OR=3.529),and a family history of diabetes(P=0.004,OR=0.228).Significant factors for hypertension included eGDR(P<0.001,OR=0.488)and skeletal muscle mass(P=0.003,OR=1.111).Significant factors for dyslipidemia included trunk fat mass(P=0.033,OR=1.202)and eGDR(P=0.037,OR=0.708).CONCLUSION Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM.BC analysis,specifically identifying visceral fat(trunk fat),may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.展开更多
The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alz...The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.展开更多
Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hip...Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.展开更多
Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced ...Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.展开更多
文摘Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical improvement as measured by evolution scales. Objectives: The present study sought to explore expectations and level of satisfaction in patients after DBS surgery with a semi-structured questionnaire and subsequent correlation with functional scales, Quality of Life (QoL), and motor and non-motor symptoms. Methods: We performed descriptive statistics to represent demographic data, Wilcoxon rank tests to determine significant differences, and Spearman correlation between the applied scales. Results: We evaluated 20 patients with a history of DBS surgery. 45% were female, with a mean age of 55.7 ± 14.15 years, a mean disease duration of 13.42 ± 8.3 years, and a mean time after surgery of 3.18 ± 1.86 years. Patients reported surgery meeting expectations in 85.5% and continued satisfaction in 92%. These two variables showed a significant correlation. Conclusions: This sample of patients remained satisfied after DBS surgery, although we found no differences in motor and non-motor clinimetric scales. Further studies are needed to confirm the importance of assessing quality of life in patients with DBS.
文摘Introduction: Complications of Urinary sphincter disorders of neurological origin can be life threatening. The objective of this study was to describe the prognosis of urinary sphincter disorders during neurological conditions. Methods: This was a six-month analytical study conducted at the neurological unit of the Hôpital national Ignace Deen. Including patients with urinary sphincter disorders following a neurological condition;Chi-square, Fischer, and Student’s t-tests were used for variables with a p value less than 0.10 and then included in a logistic model with a significance level set at 0.05 and a 95% confidence interval. Results: We collected 1081 patients among whom, 324 presented, that is to say a frequency of 30%, which concerned subjects aged 57.3 ± 16.4 years with a slight female predominance 50.3%. Urinary incontinence (80.6%) was associated with complications such as urinary tract infection with a high proportion of cerebral damage (92.3%). HIV infection (P = 0.015), bedsores (P = 0.049), and inhalation pneumonia (P = 0.001) were the main poor prognostic factors. Conclusion: Urinary sphincter disorders are elements of poor prognosis, both vital and functional, concerning elderly subjects with a predominance of urinary incontinence. HIV infection, bedsores, pneumopathy are poor prognostic factors.
文摘Intraventricular haemorrhage (IVH) is an extremely rare and poorly described complication of central nervous system Tuberculosis (CNS-TB). In this study, we report the case of a 42-year-old man who presented with a weakness of the left hemibody with diffuse headache, altered consciousness associated with fever. No notion of contagion was noted. Brain computed tomography (CT) showed a hematoma in the occipital horns of the lateral ventricles with peri-lesional oedema of the right hemisphere;after injection of contrast product (CP), there were ring-shaped contrasts in the occipital horn of the lateral ventricle and the right thalamus. Angioscan showed no aneurysms or vascular anomalies. Chest X-ray showed micronodular opacities less than 1.5 cm in size in relation to miliary. Xpert MTB/RIF of sputum and cerebrospinal fluid (CSF) showed Mycobacterium tuberculosis (MT). The patient’s course was favourable under antihypertensive and antitubercular treatment. Conclusion: This case illustrates the diagnostic difficulties of CNS-TB due to the polymorphism of the clinical and radiological presentation of CNS-TB.
文摘Approximately 20% of patients with sleep apnea will have headaches and 25% of patients with other sleep disorders will also experience headaches. We aim to evaluate sleep apnea related symptom prevalence in patient with headache presenting to neurology outpatient clinics. Twenty four patients with headache were asked for sleep apnea symptoms. The prevalence of snoring, excessive daytime sleepiness and witnessed apnea was 33.3%, 20.8% and 4.2%, respectively. Among sleep apnea symptoms, the presence of at least one symptom, at least two symptoms and all three symptoms were 9 (37.5%), 4 (16.7%) and 1 (4.2%), respectively. The frequency of major symptoms of sleep apnea syndrome was high in patient with nonspecific headache. In the light of literature review, in case of a suspicion of sleep disorder in a headache patient, it would be appropriate to question the major symptoms of OSAS, and to refer the patient to a polysomnographic evaluation for an objective diagnosis. This approach would be helpful to improve the quality of life of patients with headache.
文摘Meta-analyses are often misused and underused in neurology. This editorial provides some comments on the role of meta-analyses in neurological research.Recently, a huge increase in the number of metaanalyses and systematic reviews has been observed in neurological journals. The major strengths of metaanalyses are the increase of statistical power. However, as for any other investigative tool, meta-analytic research is a research method itself which can produce severe shortcomings. Specifically, the issues of search terms, time periods of published studies, databases used for searching, the definitions of inclusion and exclusion criteria for papers(which greatly affect clinical heterogeneity), publication bias; and the statistical methods used, dramatically influence the results of metaanalyses. The main problem of meta-analyses is that they cannot be expected to overcome the limitations of the studies they include(the so-called "garbage in,garbage out" phenomenon). Furthermore, most systematic reviews in the neurological literature lead to the unsatisfying and clinically frustrating statement "further studies are needed". However it is much more frustrating to see how the gaps in scientific knowledge identified by meta-analyses have not been translated into serious efforts to fill them. Besides their role in evaluating efficacy and tolerability of drugs, meta-analyses may be used to assess diagnostic values of debatable clinical findings, as they represent powerful tools to try to answer questions not posed by individual studies and to settle controversies arising from conflicting claims.
文摘The"Chinese Society of Neurology,Basic and Clinical Psychiatry Branch's 15tvh Academic Conference",hosted by the Chinese Society of Neurology,Basic and Clinical Psychiatry Branch and cohosted by the Shanghai Mental Health Center Affiliated to Shanghai Jiaotong University School of Medicine and the Psychology Department of the
文摘Long QT syndrome(LQTS) is a cardiac conduction disorder that predisposes patients at potentially fatal cardiac events. Inherited conditions and acquired factors contribute to LQTS. A number of frequently prescribed CNS-active drugs prolong the QT interval. The clinical neurologist may encounter LQTS when initiating a pharmacotherapy or when increasing the dosage of drugs. The clinical neurologist may also encounter LQTS during the diagnostic work-up of patients with unexplained loss of consciousness, because LQTS may present as convulsive syncope. Some studies report an association of LQTS and stroke. Awareness of LQTS may help to recognize and prevent potentially fatal cardiac events associated with LQTS. This concise article highlights the clinically most relevant aspects of LQTS in the field of neurology.
文摘Background: According to the World Health Organization, about 5% of children world-wide of 14-year-old and under have a moderate to severe developmental disability, and up to 15% of children under 5-year-old are developmentally delayed. Purpose: To determine the prevalence, socio-demographic profile, aetiologies, and the clinical presentation of developmental delay in children less than 6-year-old at the child neurology unit in a university-affiliated hospital in Yaounde. Materials and methods: It was a crosssectional descriptive study carried out in Yaounde Gynaeco-Obstetric and Paediatric Hospital (Cameroon) from August to December 2012. Children aged between 5 - 72 months with a developmental quotient less than 70 were enrolled. Developmental delay (DD) was diagnosed and classified using the Denver developmental screening test (DDST). Data concerning the child (age, gender, severity of DD), the mother (age, age at conception, educational level, marital status), history of pregnancy and delivery, perinatal and postnatal events, results of para-clinical explorations (EEG, CT-scan, genetic tests), the severity of DD and the probable or demonstrate cause of DD were recorded on a standardized questionnaire. The chisquare test was used to compare variables. Results: During the study period, 2171 children aged 5 - 72 months consulted the paediatric department of the hospital, 296 were examined at the child neurology unit of which 153 had a developmental quotient less than 70, giving a hospital prevalence of 7.0% and a prevalence of 51.7% at the child neurology unit. The mean age was 26.6 ± 18.0 months and there were 56% males. The main reason for consulting was tonus disorder (43.8%) and the developmental area of parental concern was the motor domain (90.2%). Regarding the clinical presentation, 75.2% of our population were children with cerebral palsy. DD was severe, mild, moderate and profound respectively in 14.2%, 13.5%, 12.2%, and 11.1%. Gross DD represented 90.2% of all DD children. The causes of DD were hypoxic-ischemic encephalopathy (41.8%), epilepsy (13.7%), sequelae of meningitis (6.5%), sequelae of kernicterus (6.5%), and infectious embryofoetopathies (5.2%). Conclusion: Developmental delay is frequent in paediatric neurology, with perinatal disorders being the leading aetiologies in Cameroon. Prevention of perinatal hypoxic-ischemic encephalopathy risk factors needs to be reinforced.
文摘Background: Although patients with acute headache frequently present in emergency department, the causes and predictors of short-term outcome in patients with acute headache in general neurology have not been adequately investigated. Methods: We prospectively reviewed the medical records of 130 hospitalized acute headache pa-tients in general neurology of China. Their initial CT scan was assessed, as was their lumbar puncture (LP) examination if performed. Results: The main cause of acute headache was acute secondary headache (80.8%), which was mainly attributable to acute cerebrovascular events (72.4%) followed by intracranial infection (19.0%). Among the 10.8% of patients who died during hospitalization most (85.7%) had subarachnoid hemorrhage (SAH). Significant predictors of survival were severe headache versus thunderclap headache, meningismus, de-layed loss of consciousness, and hypertension (all p < 0.05). Multiple logistic regression analyses showed significant differences in severe headache or thunderclap headache (OR, 0.255;95%CI, 0.066 - 0.990;p = 0.048) and delayed loss of consciousness (OR, 0.060;95%CI, 0.016 - 0.224, p = 0.000) between patients who died and those who survived. Conclusions: The main underlying cause of hospitalized acute headache was acute cerebrovascular events. Severe headache and delayed loss of consciousness are predictors for poor outcome of acute headache.
基金financially supported by the National Natural Science Foundation of China,No.32002235(to MT)the Science and Technology Foundation of Taian of Shandong Province,No.2020NS216(to XL)。
文摘A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.
基金supported by the Community Development Office of Hunan Provincial Science and Technology DepartmentChina,Nos.2020SK53613(to DH),21JJ31006(to DH)the Fundamental Research Funds of Central South University,Nos.CX20220375(to TX),2023zzts215(to MZ)。
文摘Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.
基金supported by grants from the Department of Science and Technology of Sichuan Province,Nos.2021ZYD0093(to LY),2022YFS0597(to LY),2021YJ0480(to YT),and 2022ZYD0076(to JY)。
文摘Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX)and 81671189(to RX)。
文摘Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.
基金supported by the National Natural Science Foundation of China,Nos.82171172(to RZ)and 81771366(to RZ)Fundamental Research Funds for the Central Universities of Central South University,Nos.2021zzts1095(to SZ)and 2022zzts0832(to HY)。
文摘Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.
基金supported by Department of Clinical and Movement Neurosciences,UCL Queen Square Institute of Neurology,London,United Kingdom,WC1N 3BGAligning Science Across Parkinson’s(ASAP)Collaborative Research Network,Chevy Chase,MD,United States(to AHVS)。
文摘Parkinson’s disease(PD,OMIM#168600)is a common neurodegenerative disorder with a global prevalence of approximately 8.5 million.PD is characterized by four cardinal motor symptoms:bradykinesia,rigidity,resting tremor,and subsequently by postural instability.It usually involves non-motor symptoms such as rapid eye movement sleep disorder,dementia,anosmia,and autonomic dysfunction.The gene glucocerebrosidase 1(GBA1),which encodes the lysosomal enzyme glucocerebrosidase(GCase)(IUBMB:EC 3.2.1.45),shows strong linkage with PD;variants of GBA1 are the commonest genetic association with PD(Sidransky et al.,2009).Several mechanisms may underlie the relationship between GBA1 mutations/variants and the molecular pathology of PD(Figure 1A and B).
基金Supported by the“SDF-sweet doctor cultivation”Project of Sinocare Diabetes Foundation,No.2022SD11 and No.2021SD09.
文摘BACKGROUND In recent years,the prevalence of obesity and metabolic syndrome in type 1 diabetes(T1DM)patients has gradually increased.Insulin resistance in T1DM deserves attention.It is necessary to clarify the relationship between body composition,metabolic syndrome and insulin resistance in T1DM to guide clinical treatment and intervention.AIM To assess body composition(BC)in T1DM patients and evaluate the relationship between BC,metabolic syndrome(MS),and insulin resistance in these indi-viduals.METHODS A total of 101 subjects with T1DM,aged 10 years or older,and with a disease duration of over 1 year were included.Bioelectrical impedance analysis using the Tsinghua-Tongfang BC Analyzer BCA-1B was employed to measure various BC parameters.Clinical and laboratory data were collected,and insulin resistance was calculated using the estimated glucose disposal rate(eGDR).RESULTS MS was diagnosed in 16/101 patients(15.84%),overweight in 16/101 patients(15.84%),obesity in 4/101(3.96%),hypertension in 34/101(33.66%%)and dyslip-idemia in 16/101 patients(15.84%).Visceral fat index(VFI)and trunk fat mass were significantly and negatively correlated with eGDR(both P<0.001).Female patients exhibited higher body fat percentage and visceral fat ratio compared to male patients.Binary logistic regression analysis revealed that significant factors for MS included eGDR[P=0.017,odds ratio(OR)=0.109],VFI(P=0.030,OR=3.529),and a family history of diabetes(P=0.004,OR=0.228).Significant factors for hypertension included eGDR(P<0.001,OR=0.488)and skeletal muscle mass(P=0.003,OR=1.111).Significant factors for dyslipidemia included trunk fat mass(P=0.033,OR=1.202)and eGDR(P=0.037,OR=0.708).CONCLUSION Visceral fat was found to be a superior predictor of MS compared to conventional measures such as body mass index and waist-to-hip ratio in Chinese individuals with T1DM.BC analysis,specifically identifying visceral fat(trunk fat),may play an important role in identifying the increased risk of MS in non-obese patients with T1DM.
基金supported by the National Natural Science Foundation of China,Nos.82072051 and 81771964(both to JG)the Natural Science Foundation of Shanghai Municipal Science and Technology Commission,No.22ZR147750(to YY)+2 种基金Science and Technology Support Projects in Biomedicine Field of Shanghai Science and Technology Commission,No.19441907500(to YY)Innovative Clinical Research Project of Changzheng Hospital,No.2020 YLCYJ-Y02(to YY)Characteristic Medical Service Project for the Army of Changzheng Hospital,No.2020 CZWJFW12(to YY)。
文摘The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,No.91849104(to YW)。
文摘Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.
文摘Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.