Recent advance of aquaporin-4 in neurodegenerative diseases / 中华神经科杂志

Neurodegenerative disease is a type of disease characterized by the progressive loss of neurons, the cause of which is not clear. Aquaporin-4 (AQP4) is a member of the aquaporin family, which plays an important role in maintaining water homeostasis in the brain. In recent years, researchers found that AQP4 has the functions of draining brain metabolic wastes and participating in material exchange through the glmphatic system. This review aims to summarize the current researches of AQP4 in the pathogenesis and progression of neurodegenerative diseases such as Parkinson′s disease and Alzheimer′s disease, and to propose future research directions.

The glymphatic system: a new exploration of the clearance of alpha-synuclein in Parkinson′s disease / 中华神经科杂志

Parkinson′s disease (PD) is a common neurodegenerative disease. Impaired balance between deposition and clearance of α-synuclein lies at the core of PD pathogenesis. The glymphatic system is a highly organized fluid transport system that is capable of removing brain waste. Emerging evidence revealed that glymphatic dysfunction plays a critical role in the pathogenesis of neurodegenerative diseases, yet study on its implication in PD is at its early stage. An in-depth study of the relationship between the function of the glymphatic system and α-synuclein clearance in PD may shed light on the pathogenesis and therapeutics of the disease.

cFos-ANAB: A cFos-based Web Tool for Exploring Activated Neurons and Associated Behaviors / 神经科学通报·英文版

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database-cFos-ANAB-a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users' purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net .

cFos-ANAB: A cFos-based Web Tool for Exploring Activated Neurons and Associated Behaviors / 神经科学通报·英文版

cFos is one of the most widely-studied genes in the field of neuroscience. Currently, there is no systematic database focusing on cFos in neuroscience. We developed a curated database—cFos-ANAB—a cFos-based web tool for exploring activated neurons and associated behaviors in rats and mice, comprising 398 brain nuclei and sub-nuclei, and five associated behaviors: pain, fear, feeding, aggression, and sexual behavior. Direct relationships among behaviors and nuclei (even cell types) under specific stimulating conditions were constructed based on cFos expression profiles extracted from original publications. Moreover, overlapping nuclei and sub-nuclei with potentially complex functions among different associated behaviors were emphasized, leading to results serving as important clues to the development of valid hypotheses for exploring as yet unknown circuits. Using the analysis function of cFos-ANAB, multi-layered pictures of networks and their relationships can quickly be explored depending on users’ purposes. These features provide a useful tool and good reference for early exploration in neuroscience. The cFos-ANAB database is available at www.cfos-db.net.

Correlation research between health empowerment and self-concealment of community elderly patients with chronic disease / 中国实用护理杂志

Objective@#To convey health empowerment and self-concealment of community elderly patients with chronic disease and the correlation between them.@*Methods@#Convenient sampling was used, elderly patients with chronic disease health empowerment questionnaire, self-concealment questionnaire, general demographic information questionnaire were used to survey 490 community elderly patients with chronic disease.@*Results@#The elderly patients′ health empowerment average score was 3.02±0.86, self-concealment average score was 3.38±0.69, health empowerment and self-concealment had significant negative correlation (r=-0.389, P<0.01).@*Conclusions@#The community elderly patients with chronic disease was at a moderate lower level, self-concealment was at a moderate higher level, relative people should decrease the degree of self-concealment of community elderly patients with chronic disease, increase the degree of health empowerment of community elderly patients with chronic disease, so as to promote the physical and psychological health of community elderly patients with chronic disease.

Correlation research between health empowerment and self-concealment of community elderly patients with chronic disease / 中国实用护理杂志

Objective To convey health empowerment and self-concealment of community elderly patients with chronic disease and the correlation between them. Methods Convenient sampling was used, elderly patients with chronic disease health empowerment questionnaire, self- concealment questionnaire, general demographic information questionnaire were used to survey 490 community elderly patients with chronic disease. Results The elderly patients′ health empowerment average score was 3.02±0.86, self-concealment average score was 3.38±0.69, health empowerment and self-concealment had significant negative correlation (r=-0.389, P＜0.01). Conclusions The community elderly patients with chronic disease was at a moderate lower level, self-concealment was at a moderate higher level, relative people should decrease the degree of self-concealment of community elderly patients with chronic disease, increase the degree of health empowerment of community elderly patients with chronic disease, so as to promote the physical and psychological health of community elderly patients with chronic disease.

The theoretical basis, experimental verification and significance of revealing meridians / 中国针灸

In this paper, scientific theory was used to prove that the meridian was the resonant channel of information energy of life, and experiment and demonstration was performed to reveal meridians to explore the significance of revealing meridian. Based on the theory of physics, biochemistry, molecular biology and information theory, the essence of meridian was demonstrated in theory. According to TCM meridian theory, acupuncture was applied at selected acupoints; the infrared thermograms of stomach meridian of foot , large intestine meridian of hand , small intestine meridian of hand , pericardium meridian of hand , heart meridian of hand , triple energizer meridian of hand , liver meridian of foot , bladder meridian of foot were recorded before and after acupuncture. As a result, thermogram recorded and showed the visual image of the meridian. It is indicated that an energy transmission network which cannot be dissected existing in the body, which was believed to be meridian. It was the resonant channel of information energy of life, and could be shown by thermogram. These experiments and theory have significance in science.

Safety and efficacy of botulinum toxin type A made in China for treatment of post-stroke upper limb spasticity: a randomized double-blind controlled trial / 中华神经科杂志

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Structure, Distribution, and Genetic Profile of α-Synuclein and Their Potential Clinical Application in Parkinson's Disease

Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy.

Experimental Identification of Mucoid Pseudomonas Aeruginosa Strains Causing Infections and Cases Review / 现代检验医学杂志

Objective To investigate the clinical distribution and antibacterial drug susceptibility of mucoid Pseudomonas aeruginosa (mPa).Methods By looking at the patients’general information,disease information and the information of anti-microbial usage,cases of 53 strains of non-repetitive mucoid Pseudomonas aeruginosa were collected from hospitalized pa-tients from Jan 2013 to Dec 2013,and drug susceptibility were analyzed.Results A total of 53 strains of mucoid Pseudo-monas aeruginosa were isolated from sputum specimen,mainly elderly patients with a mean age of 66.7±9.1 years old;50 patients had chronic history of respiratory infections,all patients were used during the hospital stay of two or more kinds of antibiotics,used jointly only 11 cases of macrolides.All strains to commonly used antimicrobial agents showed a higher sen-sitivity in vitro,in addition to ticarcillin/clavulanate (64.2%),cefepime (60.4%),other drug sensitivity was higher than 70%.Conclusion Mucoid Pseudomonas aeruginosa was susceptible to chronic respiratory infection history of the elderly,its antimicrobial susceptibility was high in vitro,the use of antimicrobial agents in clinical was combined therapy compared,but utilization rate of macrolides drugs was low.

Mutation analysis of presenilin-1 gene in Alzheimer' s disease patients and the effects of its mutation on expression of presenilin-1 and amyloid precursor protein / 中华神经科杂志

Objective To analyze the resenilin-1 (PS-1) gene mutations in Alzheimer' s disease (AD) patients and investigate the influence of the initiation codon mutation on the mRNA expression of PS-1 and amyloid precursor protein (APP) genes and the expression of PS-1 proteins.Methods (1) All 111 AD patients were enrolled by the Department of Neurology,Second Affiliated Hospital,College of Medicine,Zhejiang University from July 2004 to June 2010.Mutations in the 13 exons and flanking regions of PS-1 gene were examined by direct sequencing.(2) cDNAs encoding full-length wild-type and mutant (c.1A ＞G) PS-1 were subcloned into enhanced green fluorescent protein.Levels of the mRNA expression of PS-1 and APP genes and PS-1 proteins expression in the transfected cells were detected by quantitative real-time PCR and Western blot,respectively.Results A new heterozygous initiation codon mutation changing from ATG to GTG in one individual was identified.Compared to the control groups,the mRNA expression of the mutant PS-1 gene in HEK293 and N2a was significantly lower than the normal PS-1 gene(116.8 ± 3.9 vs 49.5 ±3.3,t =13.27,P ＜0.01 ;69.0 ± 1.9 vs 29.5 ± 1.3,t =17.20,P ＜0.01) and the APP gene was not obviously altered.The proteins were detected by Western blot analysis in HEK293 cells but not in N2a cells.Conclusions Since we only identified one novel heterozygous initiation codon mutation (from ATG to GTG),mutations in PS-1 are likely to be rare in AD patients.Initiation codon mutation would reduce the expression of PS-1 proteins.Inactivation of some of the PS-1 proteins could be insufficient to lead to AD and could be more likelv to act as a risk factor.

Mutation analysis of DJ-1 in patients with early-onset Parkinson's disease and relationship between the g.168_185del polymorphism and Parkinson's disease / 中华神经科杂志

Objective To evaluate the prevalence of the DJ-1 mutation in early-onset Parkinson's disease (EOPD) patients,and analyzed the association between the certain polymorphic marker g.168_185del in intron1 and Parkinson' s disease (PD).Methods We screened all 7 exons and exon-intron boundary regions of DJ-1 by PCR and direct nucleotide sequencing in 90 Chinese patients with EOPD.We also compared the allele and genotype frequencies of the g.168_185del polymorphism between EOPD patients and controls.Results We found no causative DJ-1 mutations in our cohort of Chinese EOPD patients.But we did identified 4 known polymorphic variants,including the g.168_185del in intron 1,g.5027G ＞ A (rs17523802),g.5065T ＞ C (rs226249),and g.5094C ＞ T (rs11121064) within exon 1.Del/Ins frequencies of the g.168_185 del polymorphism were 11.1％ (10/90)and 13.3％ (14/105) in EOPD group and normal group,respectively.Ins/Ins frequencies were 88.9％ (80/90) and 86.7％ (91/105),thex2 and P value of genotype frequency were 0.222 and 0.669 between EOPD patients and controls,respectively.The insert frequencies were 94.4％ (170/180)and 93.3％ (196/210) in EOPD patients and controls,the deletion frequencies were 5.6％ (10/180) and 6.7％ (14/210),thex2 and P value of allele frequency were 0.207 and 0.679 between EOPD patients and normal,respectively.Furthermore,the P value of genotype and allele frequencies were 0.736 and 0.744 between familial EOPD patients and controls,respectively;P values of genotype and allele frequencies were 0.847 and 0.852 between sporadic EOPD patients and control group,respectively.There was no statistical difference between groups.Conclusion Mutations in DJ-1 are uncommon in Chinese EOPD patients,and no association is observed between the DJ-1 intron 1 g.168_185del polymorphism and risk of PD.

Incidence and risk factors of cognitive impairment 3 months after first-ever stroke: a cross-sectional study of 5 geographic areas of China / 华中科技大学学报（医学）（英德文版）

This study examined the incidence, neuropsychological characteristics and risk factors of cognitive impairment 3 months after stroke in China. Five regions that differed in geography and economy in China were selected. Patients from the hospitals located in the five regions were prescreened at admission, and the demographic data, vascular risk factors and clinical characteristics of stroke were obtained. A battery of cognitive-specific domain tests was performed in the patients who failed to pass cognitive screening 3 months post stroke. Patients were diagnosed as having post-stroke cognitive impairment (PSCI) or no cognitive impairment (NCI) based on the results of the neuropsychological tests. Univariate analysis was performed for suspect risk factors, and significant variables were entered in multivariable logistic regression analysis. Our results showed that a total of 633 patients were recruited 3 months after stroke; complete cognitive tests were performed in 577 of the stroke patients. The incidence of PSCI in these Chinese patients was 30.7%. There were 129 (22.4%) patients with visuospatial impairment, 67 (11.6%) with executive impairment, 60 (10.4%) with memory impairment and 18 (3.1%) with attention impairment. The risk factors associated with PSCI were older age (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.20-2.58), low education level (OR 2.45, 95% CI 1.65-3.64), depressive symptom (OR 1.69, 95% CI 1.09-2.61), obesity (OR 2.57, 95% CI 1.41-4.71), stroke severity 3 months post stroke (OR 1.62, 95%CI 1.10-2.37) and cortex lesion (OR 1.55, 95% CI 1.04-2.31). It was concluded that PSCI occurs commonly 3 months after first-ever stroke in Chinese patients. Visuospatial ability may be the most frequently impaired cognitive domain for the patients with stroke. The critical risk factors of PSCI are older age, low education level, depressive symptom, obesity, stroke severity 3 months post stroke and cortex lesion.

Incidence and risk factors of cognitive impairment 3 months after first-ever stroke: a cross-sectional study of 5 geographic areas of China / 华中科技大学学报（医学）（英德文版）

This study examined the incidence, neuropsychological characteristics and risk factors of cognitive impairment 3 months after stroke in China. Five regions that differed in geography and economy in China were selected. Patients from the hospitals located in the five regions were prescreened at admission, and the demographic data, vascular risk factors and clinical characteristics of stroke were obtained. A battery of cognitive-specific domain tests was performed in the patients who failed to pass cognitive screening 3 months post stroke. Patients were diagnosed as having post-stroke cognitive impairment (PSCI) or no cognitive impairment (NCI) based on the results of the neuropsychological tests. Univariate analysis was performed for suspect risk factors, and significant variables were entered in multivariable logistic regression analysis. Our results showed that a total of 633 patients were recruited 3 months after stroke; complete cognitive tests were performed in 577 of the stroke patients. The incidence of PSCI in these Chinese patients was 30.7%. There were 129 (22.4%) patients with visuospatial impairment, 67 (11.6%) with executive impairment, 60 (10.4%) with memory impairment and 18 (3.1%) with attention impairment. The risk factors associated with PSCI were older age (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.20-2.58), low education level (OR 2.45, 95% CI 1.65-3.64), depressive symptom (OR 1.69, 95% CI 1.09-2.61), obesity (OR 2.57, 95% CI 1.41-4.71), stroke severity 3 months post stroke (OR 1.62, 95%CI 1.10-2.37) and cortex lesion (OR 1.55, 95% CI 1.04-2.31). It was concluded that PSCI occurs commonly 3 months after first-ever stroke in Chinese patients. Visuospatial ability may be the most frequently impaired cognitive domain for the patients with stroke. The critical risk factors of PSCI are older age, low education level, depressive symptom, obesity, stroke severity 3 months post stroke and cortex lesion.

Construction of the eukaryotic expression vector encoding IT15 gene fragment and its expression in SH-SY5Y cells / 中华神经科杂志

Objective To construct the eukaryotic expression vector encoding IT15 gene and detect its expression in SH-SY5Y cells.Methods The exon1 of IT15 gene was amplified from genomic DNA isolated from a healthy adult and a Huntington disease patient lymphoblastoid cell lines by PCR.PCR products were subcloned into eukaryotic expression vector pEGFP-C1.The SH-SY5Y cells were transiently transfected with the recombinant plasmids and observed under fluorescence microscope.Western blot was used to detect the expression of the fusion protein.Results PCR products had approximately 170 and 310 bp specific segments.The recombinant eukaryotie expression plasmids were confirmed by restriction endonuclease analysis and sequencing.The N-terminal fragment of normal huntingtin primarily localized in the cytoplasim of SH-SY5Y cells,while the N-terminal fragment of mutant huntingtin aggregated both perinuclearly and intranuelearly.Conclusions The recombinant eukaryotic expression vectors encoding wild type and mutant IT15 gene fragments are useful for studying pathogenesis of Huntington disease.The Nterminal fragment of mutant huntingtin aggregats both perinuclearly and intranuclearly,which could be important for Huntington disease pathophysiology.

Localization of the disease-causing gene coding for hereditary palmoplantar keratoderma / 基础医学与临床

Objective To identify a locus at chromosome coding for hereditary palmoplantar keratoderma of three Chinese pedigrees.Methods The genome scan was conducted with microsatellite markers on chromosome 12(D12S85、D12S368、D12S83、D12S345)and 17(D17S1868、D17S787、D17S1857、D17S798、D17S944、D17S949)respectively on the ABI 3100 Genetic Analyzer(Applied Biosystems).Two-point LOD score was calculated.Results The maximum two-point LOD score 6.59 and 5.96 at ?=0.1 were obtained at D17S1868 and D17S787 on chromosome 17q12～q21.It is an evidence of linkage between this disease and KRT9 which has been mapped within the region.Conclusion There is a locus responsible for this disease on chromosome 17q12～q21.

Gene and protein alterations in the hippocampus of rats with temporal lobe epilepsy / 中国病理生理杂志

AIM:To examine the expression profiles of both genes and proteins in hippocampus of rats with temporal lobe epilepsy(TLE)for revealing the molecular mechanisms of TLE and looking for the candidate targets and new therapeutic approaches in clinical practice.METHODS:Rat temporal lobe epilepsy was induced by administration of lithium chloride and pilocarpine(LiCl-PILO).The expression spectra of genes and proteins were constructed through the techniques of cDNA microarray,two-dimensional(2D)electrophoresis and Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS).Subsequently,the differentially expressed genes and proteins were identified and analyzed.RESULTS:There were 192 genes of differential expression observed in hippocampal tissues of LiCl-PILO-induced temporal lobe epilepsy,and 159 genes have been registered in Genbank database,in which 84 genes were up-regulated while 75 genes were down-regulated.78 protein spots of differential display were screened out,in which 31 proteins were detected to be down-regulated and 47 were up-regulated.Finally,5 proteins were identified.CONCLUSION:These genes and proteins found in our study may play pivotal roles in the pathogenic mechanisms of epilepsy and may promise new therapeutic targets for refractory epilepsy in the future.

Motor evoked potential in Parkinson's disease by transcranial magnetic stimulation / 中国病理生理杂志

AIM: To explore the characteristics of motor evoked potential(MEP) and cortical excitability in Parkinson's disease by transcranial magnetic stimulation(TMS).METHODS: 20 normal volunteers were enrolled as control(group A),with the average age of(62.3?16.7) year old ranged from 52 to 79 years including 12 males and 8 females.MEP were assessed and compared separately between left and right hemispheres.21 patients with Parkinson's disease(PD) in asymmetry symptoms were performed in this study(group B),with the average age of(63.3?16.7) year old ranged from 46 to 80 years including 12 males and 9 females.UPDRS motor scores(UPDRSⅢ) were assessed before the check of cortical excitability(MEP).Motor evoked potentials(MEP) was assessed and compared separately on the minor and the serious bodyside,compared to control group.RESULTS: The indexes of MEP from both sides of normal control had no significant diversity.Amp was increased and both rest motor threshold(RMT) and cortical latency(CL) were also decreased significantly in PD patient compared to the normal control.On the serious side of PD,RMT decreased significantly compared to the minor side.Amp,CL and central motor conduct time(CMCT) changed without significant diversity between minor and serious bodyside.CONCLUSION: The motor cortical excitability is increased in PD patients.The excitability is higher with the more serious symptom side.The character of MEP in PD patients may be helpful to make a diagnosis and evaluate the severity of symptoms.