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.

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.
alpha-Synuclein ; Alzheimer Disease ; Dopaminergic Neurons ; Lewy Bodies ; Neurodegenerative Diseases ; Parkinson Disease*

Precise and effective modification of complex genomes at the predicted loci has long been an important goal for scientists. However, conventional techniques for manipulating genomes in diverse organisms and cells have lagged behind the rapid advance in genomic studies. Such genome engineering tools have featured low efficiency and off-targeting. The newly developed custom-designed nucleases, zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system have conferred genome modification with ease of customization, flexibility and high efficiency, which may impact biological research and studies on pathogenesis of human diseases. These novel techniques can edit the genomic DNA with high efficiency and specificity in a rich variety of organisms and cell types including the induced pluripotent stem cells (iPSCs), which has conferred them with the potential for revealing the pathogenesis and treatment of many human diseases. This review has briefly introduced the mechanisms of ZFN, TALENs and CRISPR/Cas9 system, and compared the efficiency and specificity of such approaches. In addition, the application of ZFN, TALENs and CRISPR/Cas9 mediated genome modification for human disease modeling and gene therapy was also discussed.
Base Sequence ; CRISPR-Cas Systems ; genetics ; Genetic Therapy ; methods ; Humans ; Transcription Activator-Like Effector Nucleases ; genetics ; Zinc Fingers ; genetics

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.

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.

Objective To apply quality control circle ( QCC) to improve antimicrobial use correct rate treated type I incision during perioperative orthopedic. Methods The QCC group was established to grasp the current status of antimicrobial use correct rate for type I incision, set goals, analyze major factors, and form and implement countermeasures. Results The unreasonable use incidences of antimicrobial agents were decreased from 69 to 22 cases with a progress of 70%, and improved the nurse′s ability of finding and solving problems and the ability of team cooperation after conducting QCC activities. Conclusions QCC activities plays a positive role in management of orthopedic perioperative antimicrobial use, and ensures the safety of clinical application and cure rates, prevents the incision infection and postoperative nosocomial infection, increases the operation safety, and reduces the drug resistant strains.

Objective To apply quality of control circle ( QCC) to reduce the rate of low back pain (LBP) happened on medical staff. Methods The QCC activity were applied in medical staff with LBP in Orthopedic Department of West China Hospital of Sichuan University. The reasons was analyzed, and the corresponding measurements were made and implemented. The result of activity were evaluated. Results The rate of LBP were decreased significantly from 146 to 92 with a progress rate of 37. 23% and achieved rate106. 17%. This activity standardized the process of low back pain protection. Conclusions QCC activity play a positive role in reducing the rate of low back pain and it definitely can improve the health status of medical staff and their life quality.

Objective To explore the status of knowledge , attitude and practice in enhanced recovery after surgery (ERAS) among surgical medical staff, and analyze its influencing factors, so as to provide basic information for the multidisciplinary training and education program .Methods A self-designed questionnaire was used to survey 640 surgical medical staff of 17 surgical departments such as osteopathic department , gastrointestinal surgery and neurosurgery in West China Hospital of Sichuan province .The questionnaire included three parts: knowledge , attitude and practice .The SPSS 17.0 statistical software was applied for data analysis and processing.Results The score of ERAS knowledge among medical staff was (39.13±14.23). The score of reducing hospitalization time and costs was (3.30±1.30), which was the highest, while the score of anesthesia was (2.47±1.15), which was the lowest.The score of neurosurgery department was the lowest and was (25.35±12.82), while the score of general surgery was the highest and was (46.12±12.83). As for the ERAS attitude and practice of medical staff , 93.91%of medical staff agreed that ERAS could enhance patients′recovery after surgery .99.06%and 98.13%of the medical staff were willing to participate in the related study and research .41.41%of staff recently had access to relevant knowledge within one month.The most important way of acquiring knowledge was communication between colleagues and lectures . Single factor analysis showed that:there were significant difference in ERAS knowledge score among medical staff with different departments, occupation, age, job title, highest education and working experience (P<0.01).Conclusions The ERAS knowledge score of surgical medical staff is low , and their clinical practice doesn′t match their attitude .Departemnts should organize targeted ERAS training according to different characteristics of medical staff among medical staff .The ERAS should be applied into the clinical practice and better the service for patients .

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 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 .
Animals ; Fear ; Mice ; Neurons ; Proto-Oncogene Proteins c-fos ; Rats