• Volume 44,Issue 4,2019 Table of Contents
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    • Coping with the challenge of aging and strengthening the research on the prevention and control of Alzheimer’s disease

      2019, 44(4):386.

      Abstract (1257) HTML (0) PDF 962.86 K (546) Comment (0) Favorites

      Abstract:With the aggravation of aging, the impact of Alzheimer’s disease (AD) on economic and social development in China has become more and more prominent. It is urgent for China to summarize the experience in the prevention and control of AD in developed countries and systematically deploy the research system for AD prevention and control, so as to provide scientific and technological support for active and effective response to AD and contribute wisdom to overcome the challenges of diseases in human society.

    • A systemic view of Alzheimer’s disease: A new understanding of disease pathogenesis

      2019, 44(4):389.

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      Abstract:Alzheimer’s disease (AD) is the most common type of senile dementia with a high prevalence rate, but there are still no effective prevention and treatment measures. AD is regarded as a central nervous system disease in traditional views, but recent studies have shown that systemic factors are closely associated with AD. Two major pathogenic substances of AD, β-amyloid and tau protein, are metabolized in both central and peripheral pathways, and the central and peripheral clearance pathways are involved in the development and progression of AD. This article discusses the pathogenesis of AD and related prevention and treatment strategies from a systemic view.

    • Neuropsychological diagnostic procedures for dementia and related cognitive disorders

      2019, 44(4):393.

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      Abstract:

    • Grading system for evaluation and diagnosis of neurocognitive disorders in China

      2019, 44(4):397.

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      Abstract:Neurocognitive disorders (NCDs) are a group of diseases with a relatively high incidence rate. Previous studies have shown that early diagnosis and drug and/or non-drug intervention can delay or reduce NCDs, optimize the quality of life of patients and caregivers, and reduce social burden. Although the total number of patients with NCDs in China is increasing year by year, the diagnostic rate of NCDs remains at a low level. This article analyzes the possible reasons for the low diagnostic rate and proposes a grading system for the evaluation and diagnosis of NCDs in China. cells,and the most significant inhibition of proliferation. Conclusion:5-FC and GCV combined with ultrasound microbubbles loaded with the CD-TK double suicide gene can promote the apoptosis and inhibit the proliferation of lung cancer cells and thus have a marked killing effect on lung cancer.

    • Advances in clinical trials on new drugs for Alzheimer's disease

      2019, 44(4):401.

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      Abstract:Alzheimer’s disease is a neurodegenerative disorder with the clinical manifestations of cognitive impairment and reduced abilities of daily living. At present, the most important pathogenesis of AD is neuron apoptosis due to senile plaques caused by amyloid β-protein deposition and neurofibrillary tangle caused by hyperphosphorylation of Tau protein. The drugs launched for the treatment of AD include cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. Many drugs for the treatment of AD have entered phase III clinical trials over the past 20 years, including innovative class 1 chemicals in China. This article reviews the clinical studies on drugs for the treatment of AD.

    • Research advances in cognitive impairment induced by type 2 diabetes

      2019, 44(4):404.

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      Abstract:Both type 2 diabetes and cognitive impairment are chronic diseases that greatly threaten the quality of life of human beings, and they are also important health issues in the elderly population. The incidence rates of these two diseases keep increasing in most parts of the world. The pathogenesis of cognitive impairment caused by type 2 diabetes remains unclear, and possible factors and mechanisms include insulin resistance, hyperinsulinemia, association between insulin and β-amyloid metabolism, an increase in advanced glycation end products due to hyperglycemia, hypoglycemia, cerebrovascular diseases, dyslipidemia, and inflammatory factors. This article reviews the various factors and mechanisms of cognitive impairment caused by type 2 diabetes, in order to provide ideas for prevention and early intervention of cognitive impairment including Alzheimer’s disease.

    • Research advances in diagnosis and treatment of rapidly progressive dementia associated with autoimmune encephalitis

      2019, 44(4):411.

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      Abstract:Autoimmune encephalitis (AE) is an important curable cause of rapidly progressive dementia, and early diagnosis and treatment of AE is the key to the improvement of prognosis. This article reviews rapidly progressive dementia associated with AE from the aspects of epidemiology, pathogenesis, and diagnosis and treatment.effects on cellular protein synthesis,proliferation and autophagy flux of the downstream signals involved in. Methods:Immunohistochemistry and Western blot were used to detect the expressions of DDIT4,pS6K1,p4E-BP1 and LC3 Ⅱ/Ⅰ in 15 cases of human skin BCC and 15 cases of normal skin tissues respectively. Results:The expression of DDIT4(0.247±0.152,P=0.005) in BCC was significantly inhibited as compared with that in the normal tissues. Meanwhile the expression of p4E-BP1(0.290±0.169,P=0.015) and ratio of LC3 Ⅱ/Ⅰ(0.692±0.154,P=0.007) were decreased,but the expression of pS6K1 (0.837±0.050,P=0.000) was significantly increased. Conclusion:DDIT4 expression is inhibited in human BCC cells,which may promote the downstream protein synthesis and proliferation,and inhibit the autophagy flux through the mTORC1 pathway to finally involve in the pathogenesis and development of BCC. DDIT4 and its downstream signals may serve as target for the further treatment and prognosis of BCC.

    • Research advances in medical decision-making for advanced dementia

      2019, 44(4):415.

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      Abstract:Dementia remains an incurable disease at present and has brought heavy social burden which is increasing year by year. Patients with dementia and their caregivers are always faced with a lot of physical and psychological needs in the end stage of life. Therefore, treatment for patients with advanced dementia should focus on the prevention and alleviation of pain, so as to improve their quality of life. Effective palliative treatment of patients with advanced dementia and appropriate medical decisions, which meet the needs of patients and their families, can improve their symptoms, increase the degree of comfort, and reduce the burden of caregivers. This article reviews the research advances in medical decision-making for patients with advanced dementia.

    • Research advances in the Wnt/β-catenin signaling pathway in neuronal degeneration in Alzheimer’s Disease

      2019, 44(4):419.

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      Abstract:Objective: Alzheimer’s disease (AD) is the most common type of dementia in the elderly, but its pathogenesis is complex and remains unclear. The most common neuropathological features of AD include amyloid β-protein (Aβ) deposition, neurofibrillary tangles due to hyperphosphorylation of Tau protein, and the activation of brain neuroinflammation, with neuronal injury and impaired learning and memory abilities. A growing number of studies have shown that the Wnt/β-catenin signaling pathway plays an important role in neurodegenerative disorders, especially in AD. This article reviews the related literature to clarify the association of the Wnt/β-catenin signaling pathway with the pathogenesis of AD, Aβ deposition, Tau protein, and neuroinflammation and related mechanism. Methods: The articles on the association of the Wnt/β-catenin signaling pathway with AD, Aβ neurotoxicity, Tau protein phosphorylation, and neuroinflammation, published in China and foreign countries, were reviewed. Results: Studies showed that the Wnt/β-catenin signaling pathway was involved in the development and progression of AD. The activation of this pathway inhibited Aβ deposition, hyperphosphorylation of Tau protein, and neuroinflammation, and on the contrary, it promoted the formation and aggregation of Aβ, the phosphorylation of Tau protein, and the development of neuroinflammation. Conclusion: This article reviews the importance of the Wnt/β-catenin signaling pathway in the pathogenesis of AD and provides a theoretical basis for the research on the pathogenesis of AD. It is pointed out that activation of the Wnt/β-catenin signaling pathway may be used as a potential target for the treatment of AD.patients,who were diagnosed with NSCLC in Sichuan Provincial People’s Hospital(as observation group),and 50 healthy people(as control group). Assay kits were used to determine the levels of superoxide dismutase(SOD),malondialdehyde(MDA),and catalase(CAT) in plasma. The mRNA and protein expression of Klotho in plasma was measured/determined by qPCR and Western blot,respectively. Pearson correlation analysis was performed for the correlation between Klotho expression level and oxidative stress. Klotho methylation level was determined by methylation-specific PCR(MS-PCR). The methylation rate of CpG islands was determined by pyrosequencing. Results:Compared with the control group,the observation group had significantly reduced levels of SOD[(79.86±18.24) mU/L vs. (94.56±16.40) mU/L,t=4.487,P=0.000] and CAT[(18.50±4.62) U/mg vs. (25.26±3.54) U/mg,t=8.605,P=0.000],but there was no significant difference in MDA level between the observation group and the control group[(2.87±2.26) pg/mL vs. (2.52±1.06) pg/mL,t= 1.675,P=0.097]. The mRNA and protein expression levels of Klotho in plasma were significantly lower in the obser-vation group than in the control group(mRNA:0.66±0.16 vs. 1.04±0.10,t=14.93,P=0.000;protein:0.70±0.20 vs. 1.04±0.10,t=10.92,P= 0.000). There was a positive correlation between the protein expression of Klotho and the levels of SOD(r=0.768,P=0.000) and CAT(r=0.708,P=0.000). Meanwhile,the observation group had an increased methylation level of CpG islands in the Klotho promoter. Conclusion:Klotho methylation may be a clinical marker of oxidative stress in the plasma of patients with NSCLC.

    • Naringenin alleviated the SH-SY5Y cells death and insulin resistance by activating mTOR/p70S6K signalling pathway in oxidative stress induced by H2O2

      2019, 44(4):424.

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      Abstract:Objective:To investigate the effect of naringenin on SH-SY5Y cells of neuroblastoma in oxidative stress induced by H2O2 and the possible mechanism. Methods:Firstly,a concentration of H2O2 that caused half cells death was chosen by CCK-8 assay. Three concentrations of naringenin(20,40,80 μmol/L) were added into H2O2-treated media,and cells survival rates were tested by CCK-8 assay after 4 hours. An optimal concentration of naringenin was chosen for the next experment in naringenin group. Next,three groups were chosen for the next experiment(control group:cells without any treatment;H2O2 group:cells with 600 μmol/L H2O2;H2O2+NAR group:cells with 600 μmol/L H2O2 and 40 μmol/L NAR simultaneously). The apoptosis rate was measured by Annexin V-FITC/PI Apoptosis Detection Kit,intercellular reactive oxygen species(ROS) was measured by fluorescent probe through flow cytometry,and mTOR/p70S6K signalling pathway-related protein[mTOR,p-mTOR(Ser2448),p70S6K,p-p70S6K(Thr389)] were tested by Western blot. Finally,insulin resistance-related protein insulin receptor substrate 1(IRS1) and phosphorylated IRS1 in serine 636 and serine 639[p-IRS1(Ser636+Ser639)] were detected by Western blot as well. Results:H2O2 significantly increased the SH-SY5Y cells death,apoptosis,intercellular ROS and p-IRS1(Ser636+Ser639),and decreased the protein expression of p-mTOR(Ser2448) and p-p70S6K(Thr389) compared with control group(P<0.05). These effects were attenuated after NAR treatment,compared with H2O2 group(P<0.05). Conclusion:Naringenin reduced the ROS accumulation and the SH-SY5Y cells death. The activation of mTOR/p70S6K signalling pathway and decreasing of insulin resistance may be involved in naringenin-induced antioxidative effects.

    • Protective effect of EGCG on neurosynaptic damage in APP/PS1 double transgenic mice

      2019, 44(4):430.

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      Abstract:Objective:To study the protective effect of EGCG on neurosynaptic damage in APP/PS1 double transgenic mice and its possible mechanism. Methods:APP/PS1 double transgenic mice were randomly divided into two groups:model group(0.1 mL/10 g,normal saline infusion),EGCG group[20 mg/(kg?d),EGCG infusion]. Ten negative mice in the same sex were treated with normal group(0.1 mL/10 g,normal saline infusion). Morris water maze was used to test the escape latency and platform-crossing changes of mice in each group. Electron microscopy was used to observe the damage of hippocampal neurons in each group. Immunohistochemi-cal method was used to detect the expression of PSD95 and GAP43 in hippocampus of mice. RT-PCR was used to detect the content of PSD95 mRNA and GAP43 mRNA in hippocampus of mice. Results:The escape latency of the model group was significantly pro-longed,the hippocampal neurons were severely damaged,the expression of PSD95 was decreased,and the expression of GAP43 was increased. The results of immunohistochemistry showed that the average optical density of PSD95 in EGCG group was higher than that in model group[(0.11±0.03) vs. (0.05±0.02),P=0.001] and that of GAP43 in EGCG group was lower than that in model group [(0.10±0.03) vs. (0.16±0.04),P=0.002]. The results of RT-PCR showed that the expression of PSD95 in EGCG group was higher than that in model group[(0.82±0.11) vs. (0.50±0.06),P=0.000]. The expression of GAP43 in EGCG group was lower than that in model group[(1.12±0.11) vs. (1.56±0.16),P=0.000]. Conclusion:EGCG can significantly improve the spatial learning,memory and synaptic damage of APP/PS1 transgenic mice. The mech-anism may be related to the effect of EGCG on the synaptic structure of hippocampus,the increase of PSD95 expression and the down-regulation of GAP43 expression.

    • A bioinformatics analysis of differentially expressed genes in Alzheimer’s disease

      2019, 44(4):434.

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      Abstract:Objective: To investigate the differentially expressed genes (DEGs) in different stages of Alzheimer’s disease (AD) through a bioinformatics analysis and the pathogenesis of AD at the molecular level, and to provide new ideas for the research on AD. Methods: The microarray dataset GSE28146 was downloaded from gene expression omnibus (GEO), and the GEO2R online software was used to screen out DEGs between the control group and the mild/moderate/severe AD groups. The DAVID database was used to perform genetic ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs, the STRING database was used to establish a protein-protein interaction network, and the Cytoscape software was used to screen out the hub genes. Results: A total of 881, 896, and 1142 DEGs were screened out in the mild, moderate, and severe AD groups, respectively, compared with the control group. The GO functional enrichment analysis showed that the DEGs in the mild AD group were closely associated with the activation of apoptosis-related processes, regulation of immune response, and protein phosphorylation, those in the moderate AD group were closely associated with inflammatory response, apoptosis regulation, and release of calcium ions, and those in the severe AD group were closely associated with the activation of nuclear factor-kappa B, protein phosphorylation and dephosphorylation, and degradation of extracellular matrix. The KEGG analysis showed that the DEGs in the mild AD group were mainly enriched in the p53 and TGF-h signaling pathways, those in the moderate group were mainly involved in the signaling pathways of cancer, natural killer cell-mediated cytotoxicity, and cell adhesion molecules, and those in the severe AD group were mainly enriched in the signaling pathways involving cell cycle, Hippo signaling pathway, and neuroactive ligand-receptor interaction. The protein-protein interaction network analysis showed that the top 5 hub genes with the highest degree of enrichment were GART, EHMT2, KRAS, ESR1, and CD44 in the mild AD group, CBLB, HERC1, UBE2G1, UBE2M, and HECW2 in the moderate AD group, and UBE2C, SOCS3, FBXW7, UBE3B, and UBA6 in the severe AD group. Conclusion: The bioinformatics analysis of different stages of AD shows that the enriched signal pathways and the hub genes may play an important role in the development and progression of AD, which provide a basis and new ideas for further research on AD.

    • Evaluation of neuropsychiatric symptoms in patients with mild cognitive impairment and Alzheimer’s disease from the Memory Disorder Clinic

      2019, 44(4):441.

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      Abstract:Objective:To examine the prevalence of neuropsychiatric symptoms(NPSs) in patients with mild cognitive impairment (MCI) and Alzheimer’s disease(AD) from the Memory Disor-der Clinic of the Department of Geriatrics,The First Affiliated Hospital of Chongqing Medical University. Methods:A total of 169 patients with MCI(diagnosed according to the Petersen cri-teria) and 308 patients with AD(diagnosed according to the NINCDS-ADRDA criteria;192 were classified as mild,84 as moderate,and 32 as severe),who attended the Memory Disor-der Clinic of the Department of Geriatrics,The First Affiliated Hospital of Chongqing Medical University,from January 2014 to June 2017,were included in this study. Neuropsychological examination was conducted for all patients and their caregivers,and the demographics of all patients were recorded. NPSs and the severity of AD were assessed by the Neuropsychiatric Inventory and Clinical Dementia Rating,respectively. Results:One or more NPSs were identified in 49.1% of patients with MCI,79.7% of patients with mild AD,96.4% of patients with moderate AD,and 100.0% of patients with severe. Delusion,hallucination,anxiety,apathy,irritability,and aberrant motor activity were significantly more prevalent in the mild AD group than in the MCI group( χ2=19.448,7.873,12.386,11.756,7.743,and 13.390,respectively,all P<0.016 7). These differences remained statistically significant after adjust-ment for age,sex,and education level by logistic regression analysis[odds ratio(OR)(95% confidence interval(CI))=3.54(1.91-6.54),2.87(1.32-6.26),2.37(1.37-4.10),2.34(1.37-4.00),2.15(1.28-3.58),and 9.41(2.12-41.71),respectively,all P<0.05]. All NPSs except irritability were significantly more prevalent in the moderate AD group than in the mild AD group(all P<0.016 7). These dif-ferences remained statistically significant after adjustment for age,sex,and education level by logistic regression analysis(all P<0.05). Furthermore,disinhibition,aberrant motor activity,and sleep disturbance were significantly more prevalent in the severe AD group than in the moderate AD group(χ2=17.673,9.995,and 16.987,respectively,all P<0.016 7). These differences remained statistically significant after adjustment for age and education level by logistic regression analysis[OR(95%CI)=6.93(2.55-18.80),4.85(1.71-13.78),and 9.63(3.17-29.27),respectively,all P<0.05]. There was no significant difference in the prevalence of NPSs between female and male patients with MCI(P>0.05). However,delusion and depression were significantly more prevalent among female than among male patients with AD( χ2=8.609 and 23.560,respectively,both P<0.05). These differences remained statistically signifi-cant after adjustment for age and education level by logistic regression analysis[OR(95%CI)=2.18(1.32-3.58) and 3.22(1.83-5.66),respectively,both P<0.05]. Conclusion:NPSs become more prevalent as disease progresses in patients with cognitive impairment,and female AD patients have higher risk of developing delusion and depression than male AD patients.

    • Effect of similarities test in the diagnosis of mild cognitive impairment and Alzheimer's disease

      2019, 44(4):448.

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      Abstract:Objectives: To evaluate the value of similarities test (ST) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: One hundred and twenty-five patients with amnestic MCI-single domain (aMCI-SD), 160 patients with amnestic MCI-multiple domain (aMCI-MD), 139 AD patients, and 132 normal controls were all evaluated by a complete set of neuropsychological tests including ST. Among these tests, Mini-Mental State Examination and Auditory-Verbal Learning Test were used for preliminary screening, and further evaluation and examination were carried out according to the screening results.. The similarities test consisted of 13 items, and each item was scored at three levels: 0, 1 and 2, with a maximum score of 26. Results: The total scores of the four groups were then compared, and the results showed that there were significant differences (r = 0.15-0.47, P <0.01). ST scores were found to have a significant correlation with the scores of tests reflecting language function such as Animal Fluency Test and Boston Naming Test. The area under the ROC curve of ST score (total score: 26; cut-off score: 12) for the diagnosis of AD was 0.881 (95% confidence interval: 0.842-0.920, P <0.01). Conclusion: ST with 13 items can be used to test language-related cognitive function and is effective for identifying aMCI-SD, aMCI-MD, and AD patients.

    • Effect of cognitive behavioral therapy on treatment compliance and immune function in children with cancer receiving chemotherapy

      2019, 44(4):452.

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      Abstract:Gu Ying, Yu Xiaoping, Zhu Yuan, Huang Yongyan, Shen Ying, Chang Yujie, Yu Lan (Department of Geriatrics, Rui Jin Hospital Shanghai Jiao Tong University School of Medicine) 【Abstract】Objective: To investigate the current status of safety management in hospitalized elderly patients with dementia, safety management issues in nursing of such patients, and feasible nursing intervention measures. Methods: Seven experts engaged in geriatric nursing were interviewed by trained interviewers through semi-structured interviews, and a questionnaire survey was conducted among 300 nurses in Department of Geriatrics and Department of Neurology in six tertiary hospitals and one secondary hospital specialized in geriatrics in Shanghai, China. Results: Of all nurses, 86.60% thought that hospitalized elderly patients with dementia had more nursing safety issues than other elderly patients, including falls, drug misuse, getting lost, pressure ulcers, accidental extubation, aspiration, self-harm, and hurting other persons. Of all nurses, 70.79% believed that such patients might get lost, 63.23% thought they might experience drug misuse, 47.76% thought they might suffer from pressure ulcer, 66.32% thought falls might occur in these patients, and 63.57% thought they might experience accidental extubation. At present, there are no special questionnaires and labels for hospitalized elderly patients with dementia. Specialized caretakers may help to reduce the incidence rates of unsafe incidents in hospitalized elderly patients with dementia. Conclusion: Establishment of a safety management model for hospitalized elderly patients with dementia in China is a key issue which should be taken Objective: To investigate the current status of safety management in hospitalized elderly patients with dementia, safety management issues in nursing of such patients, and feasible nursing intervention measures. Methods: Seven experts engaged in geriatric nursing were interviewed by trained interviewers through semi-structured interviews, and a questionnaire survey was conducted among 300 nurses in Department of Geriatrics and Department of Neurology in six tertiary hospitals and one secondary hospital specialized in geriatrics in Shanghai, China. Results: Of all nurses, 86.60% thought that hospitalized elderly patients with dementia had more nursing safety issues than other elderly patients, including falls, drug misuse, getting lost, pressure ulcers, accidental extubation, aspiration, self-harm, and hurting other persons. Of all nurses, 70.79% believed that such patients might get lost, 63.23% thought they might experience drug misuse, 47.76% thought they might suffer from pressure ulcer, 66.32% thought falls might occur in these patients, and 63.57% thought they might experience accidental extubation. At present, there are no special questionnaires and labels for hospitalized elderly patients with dementia. Specialized caretakers may help to reduce the incidence rates of unsafe incidents in hospitalized elderly patients with dementia. Conclusion: Establishment of a safety management model for hospitalized elderly patients with dementia in China is a key issue which should be taken seriously by nursing staff in Department of Geriatrics.

    • A visualized analysis of research articles on senile dementia nursing in China and foreign countries in 2012-2017

      2019, 44(4):456.

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      Abstract:Objective: To perform a visualized analysis of research articles on senile dementia nursing in China and foreign countries, to investigate the difference in research hotspots in this field between China and foreign countries, and to provide directions for the research on high-quality dementia nursing in China. Methods: With dementia and nursing as key words, CINAHL, PubMed, Embase, ScienceDirect, Cochrane, Wanfang Data, CNKI, and VIP were searched for research articles on senile dementia nursing in China and foreign countries published from 2012 to 2017. A total of 2195 English articles and 1289 Chinese articles were obtained, and with the help of EviGate data platform, an intelligent information processing system was used for large-scale data extraction and information analysis, and the relevant graph was plotted. Results: In 2012-2017, self-ability of the elderly or elderly patients was the major direction of research on senile dementia nursing in foreign countries, followed by care of the elderly or elderly patients by others and the two-way influence of external environment or care model on the elderly; in China, the research on geriatric nursing mainly focused on self-capacity of the elderly or elderly patients and care behavior of others. The research on dementia nursing attracts more attention in foreign countries than in China, and compared with those in China, research articles in foreign countries had better quality, focused on more hotspots, and involved several areas including policies, scales, and soothing care, which were not covered by the research articles in China. Conclusion: This literature search has shown that compared with the research on senile dementia nursing in foreign countries, the research on this field in China has its own advantages and disadvantages. Therefore, it is urgent to explore and establish theoretical and practical systems for senile dementia nursing in China.

    • α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (GluR1): a case report

      2019, 44(4):461.

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      Abstract:

    • Clinical diagnosis and treatment of Parkinson’s disease in China: Current status and research advances

      2019, 44(4):464.

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      Abstract:Parkinson’s disease (PD) is one of the most common neurodegenerative diseases at present, and with the advent of aging society, there are significant increases in the incidence, prevalence, and mortality rates of this disease. A correct understanding of PD, continuous improvement of the accuracy of clinical diagnosis, and improvement in early diagnostic rate may help to actively cope with this challenge. With reference to the recent studies in related centers in China, this article reviews the current status of the diagnosis and treatment of PD and introduces the establishment of PD Biobank, the research on imaging and humoral markers, and the updates in treatment and related guidelines, in order to explain the current status of PD diagnosis and treatment and research advances in China over the past three years.

    • Advances in the basic research on Parkinson’s disease

      2019, 44(4):468.

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      Abstract:Parkinson’s disease (PD) is a common degenerative disease in the central nervous system, with movement disorder as the main clinical feature and chronic loss of dopaminergic neurons in the substantia nigra as the main pathological feature. The pathogenesis of PD has not been fully clarified so far. In recent years, important achievements have been made in the basic research on PD in China and foreign countries. This article briefly reviews these research advances from the following five aspects: abnormal aggregation of α-synuclein in the brain, association between gut-brain axis and PD, molecular mechanism for the death of dopaminergic neurons, mitochondrial dysfunction and oxidative stress, and the role of glial cells and peripheral immune cells in the pathogenesis of PD. These advances show that PD is a systemic disease involving not only dopaminergic neurons and glial cells in the brain, but also peripheral immune cells and other tissue and organs. Such new understanding will help to promote the future development of accurate diagnostic and therapeutic approaches.

    • Research hotspots and development trends of α-synuclein

      2019, 44(4):473.

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      Abstract:Objective:To investigate the research hotspots and development trends in the field of α-synuclein(αS). Methods:CiteS-pace V was used for the visualization processing and analysis of 10 991 articles on αS in Web of Science Core Collection database from 1998 to 2017,to reveal the knowledge basis,research hotspots,and development trends of αS research. Results:The numbers of published articles and citations in the research on αS showed an exponential increase year by year. The US contributed significantly to the research in the field of αS. The high-frequent co-cited articles on αS mainly focused on the association between αS and Lewy body,αS gene mutations,αS aggregation,and Braak stages of Parkinson’s disease. The main research hotspots in the field of αS in-cluded αS-related diseases,in vitro studies,and the pathogenesis of Parkinson’s disease. The research frontiers and future research trends of αS were expected to focus on the biomarkers,autophagy and other pathogeneses,neuroprotective therapy,and mouse model of Parkinson’s disease. The scholars in China paid more attention to the pathogenesis and animal model of Parkinson’s disease. Conclusion:The research on αS has been developing rapidly around the world in recent years. This article analyzes the knowledge basis,research hotspots,and development trends of the research on αS and reveals the dynamic development of αS research over the past twenty years,which provides a reference for research in related disciplines.

    • Role of Survivin during the process of neuronal apoptosis in a rat model of Parkinson’s disease

      2019, 44(4):481.

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      Abstract:Objective:To investigate the effect of Survivin on neuronal apoptosis in the substantia nigra in a rat model of Parkinson’s disease(PD). Methods:Healthy adult male Sprague Dawley rats were randomly divided into 4 groups:control(n=8);PD(n=8);PD + adenovirus empty vector(n=8);and PD + Survivin(n=8). Following 1 week of model induction,rats from the control and PD group received normal stimulation with no intervention,rats from the PD + adenovirus empty vector group received an empty adenovirus vec-tor injection in the substantia nigra,and rats from the PD + Survivin treatment group received an injection of Survivin adenovirus in the substantia nigra. Behavioral evaluation of spontaneous rotation was performed by injecting apomorphine(APO) every week follow-ing completion of the treatment. Following behavioral testing,brain tissue was collected. Neuronal apoptosis in the substantia nigra was determined by TUNEL staining. qRT-PCR and western blot were used to determine mRNA and protein levels of Caspase 3 and 9,respectively. Results:Compared to the PD + adenovirus empty vector group,the PD + Survivin treatment group exhibited significantly fewer spontaneous rotations following treatment(F=22.315,P=0.000,P=0.000). Compared with the PD group and the PD + adenovirus empty vector group,neuronal apoptosis was signifi-cantly reduced in the PD + Survivin treatment group(F=38.912,P=0.000,P=0.000). Compared with the control group,mRNA expression of Caspase-3 and 9(F=338.429,P=0.000,P=0.000;F=283.352,P=0.000,P=0.000) and protein expression of cleaved Caspase-3 and 9(F=640.262,P=0.000,P=0.000;F=354.210,P=0.000,P=0.000) were significantly decreased. Conclusion:Sur-vivin can inhibit apoptosis in the brain by inhibiting Caspase-3 and -9 at the mRNA and protein expression level in rat model of Parkinson’s disease,resulting in protection against neurodegeneration in the substantia nigra and reduced Parkinson’s disease-related symptoms.

    • A Meta-analysis of association between diabetes mellitus and the risk of Parkinson’s disease

      2019, 44(4):487.

      Abstract (981) HTML (0) PDF 1.46 M (667) Comment (0) Favorites

      Abstract:Objective: To systematically review the association between diabetes mellitus (DM) and the risk of Parkinson’s disease (PD). Methods: PubMed, CNKI, Wanfang Data, and VIP were searched for related articles published up to March 2016. Case-control studies on PD and DM were retrieved, related data were extracted, and Review Manager 5.3 was used for data analysis. Results: Seven articles which met the inclusion criteria were included in the meta-analysis, with a total of 5143 PD patients and 5713 controls. Data processing showed that in spite of significant heterogeneity (I2 = 76%, P <0.010), the incidence rate of diabetes was negatively correlated with the incidence rate of PD [odds ratio (OR)=0.62, 95% confidence interval(CI)=0.41 to 0.94]. Due to significant heterogeneity in data, subgroup analysis was performed based on the mean age at the time of PD diagnosis and smoking history, and the results showed that for PD in patients aged ≤67.2 years(OR=0.35,95% CI=0.21 to 0.59), in patients aged >67.2 years(OR=0.69,95%CI=0.38 to 1.24), and in patients with a history of smoking(OR=0.56,95%CI=0.33 to 0.94) and in patients without a history of smoking(OR=0.74,95%CI=0.27 to 1.99). In addition, the sensitivity analysis confirmed the reliability of the above results. Conclusion: The results of the case-control studies suggest that DM may reduce the incidence rate of PD despite of significant heterogeneity. Further studies focusing on the common pathogenesis of DM and PD and the pathogenic factors interacting with one another are needed to investigate the association between DM and PD.

    • Negative feedback regulation of hypothalamic-pituitary-adrenal axis activity by glucocorticoid in bipolar disorder

      2019, 44(4):493.

      Abstract (1588) HTML (0) PDF 1.33 M (853) Comment (0) Favorites

      Abstract:Bipolar disorder (BD) is a major subtype of mood disorders, and major depressive disorder (MDD), also called unipolar depression, is another important subtype of mood disorders. BD is characterized by cyclical alterations of depressive and maniac symptoms. Both BD and MDD are serious diseases which greatly affect human mental health. Dysfunction of stress response systems including the hypothalamic-pituitary-adrenal (HPA) axis has been confirmed to be an important pathogenesis of mood disorders. However, there is still a lack of systematic studies on HPA axis activity in BD patients. Most of the existing studies only focus on the changes in the levels of plasma cortisol and salivary cortisol, with a great difference in results between these studies; however, dexamethasone/corticotropin-releasing hormone test has achieved relatively consistent results from the studies and has shown a significant reduction in cortisol inhibition, suggesting an abnormal negative feedback regulation function of the HPA axis in BD patients. Glucocorticoid receptor (GR) and FK 506 binding protein 51 (FKBP51), a member of the immunophilin family, are two important molecules involved in the negative feedback regulation of the HPA axis. On the one hand, single nucleotide polymorphism of the GR gene is thought to be associated with the onset of BD; on the other hand, childhood trauma may increase the risk of BD, possibly by affecting the sensitivity of the HPA axis, and GR and FKBP51 are involved in the regulation of the sensitivity of the HPA axis during this process. This article reviews the recent studies on abnormal HPA axis activity in BD patients and disorder in negative feedback regulation of the HPA axis caused by GR and FKBP51, in order to provide new ideas for research on the pathogenesis of BD associated with stress response.

    • The heterogeneity of senile depression and its diagnostic and therapeutic protocols

      2019, 44(4):501.

      Abstract (888) HTML (0) PDF 720.82 K (578) Comment (0) Favorites

      Abstract:Senile depression refers to depression that occurs after the age of 65, including the first depression occurring in old age and recurrent depression from earlier age of onset. Depression includes not only major depressive disorder, but also various types of depression. Many cases of senile depression are comorbid with organic diseases such as degenerative brain diseases and cerebrovascular impairment, and are affected by other factors including physical disease, environmental factors, and previous depressive episodes. Here, the heterogeneity of senile depression will be discussed to distinguish between different types of senile depression, suggest the corresponding diagnostic and therapeutic protocols, and provide references for clinical research, diagnosis, and treatment.

    • Clinical research advances in the effect of acupuncture and moxibustion in treatment of several major brain diseases

      2019, 44(4):504.

      Abstract (1094) HTML (0) PDF 854.45 K (466) Comment (0) Favorites

      Abstract:Objective: To investigate the clinical research advances in the effect of acupuncture and moxibustion in the treatment of autism spectrum disorders (ASD), depression, and senile dementia. Methods: With the method of a retrospective literature review, CNKI, VIP, Wanfang Data, and PubMed were searched for articles on the effect of acupuncture and moxibustion in the treatment of the above three brain diseases, and data analysis was performed based on etiology, pathogenesis, and principle of treatment. Results: Extensive research has been carried out on acupuncture and moxibustion for the treatment of the three brain diseases in recent years, and the large number of clinical studies had laid a foundation for the applicability and scientificity of this treatment. Conclusion: Acupuncture and moxibustion have a marked clinical effect in the treatment of brain diseases. Clinical practice guidelines of acupuncture and moxibustion should be published as soon as possible to standardize future clinical studies.

    • Effect of anti-Lingo-1 antibody on oligodendrocytes in the hippocampal dentate gyrus in rats with depression and cognitive impairment

      2019, 44(4):508.

      Abstract (1162) HTML (0) PDF 1.74 M (428) Comment (0) Favorites

      Abstract:Objective: To investigate the effect of anti-Lingo-1 antibody on oligodendrocytes in the hippocampal dentate gyrus (DG) in rats with depression and cognitive impairment. Methods: After 1 week of adaptive feeding, 70 clean male Sprague-Dawley rats aged 4-6 weeks were randomly divided into control group with 10 rats and model group with 60 rats. A rat model of depression with chronic unpredictable stress (CUS) was established for 4 weeks. The sucrose preference test was used to screen out 23 model rats, and then these rats were randomly divided into CUS groups with 12 rats and anti-Lingo-1 group with 11 rats. The Morris water maze was used to assess the behavioral level of the control group, the CUS group, and the anti-Lingo-1 group, and the stereological method was used to calculate the number of oligodendrocytes in the hippocampal DG for all groups. Results: After 4 weeks of CUS stimulation, compared with the control group, the CUS group had a significant reduction in the number of platform crossings on day 6 (2.4±0.2 vs 3.4±0.2, F = 20.049, P = 0.004); after 3 weeks of anti-Lingo-1 antibody treatment, the anti-Lingo-1 group had a significant increase in the number of platform crossings compared with the CUS group (4.3±0.3 vs 2.4±0.2, F = 20.049, P = 0.000). The stereological results showed that compared with the control group, the CUS group had a significant reduction in the number of oligodendrocytes in the hippocampal DG [(3.1±1.3)×104 vs (4.9±1.1)×104, F = 8.747, P = 0.026); compared with the CUS group, the anti-Lingo-1 group had a significant increase in the number of oligodendrocytes in the hippocampal DG [(6.1±1.1)×104 vs (3.1±1.3)×104, F = 8.747, P = 0.001). Conclusion: Anti-Lingo-1 antibody can improve cognitive impairment in rats with depression. The effect of anti-Lingo-1 antibody on oligodendrocytes in the hippocampal DG in rats with depression and cognitive impairment might be one of the important structural bases for anti-Lingo-1 antibody in improving cognitive impairment in rats with depression.

    • Risk factors for post-stroke depression in rehabilitation stage

      2019, 44(4):515.

      Abstract (1069) HTML (0) PDF 805.40 K (406) Comment (0) Favorites

      Abstract:Objective:To investigate the incidence rate of post-stroke depression(PSD) in rehabilitation stage and related risk factors,as well as the symptoms of PSD which should be taken seriously in this stage. Methods:A cross-sectional survey was performed among 126 patients with stroke who were treated in Department of Rehabilitation Medicine in two grade A tertiary hospitals from March 2017 to January 2018. The Self-rating depression scale was used to evaluate the symptoms of depression,and related influencing factors were analyzed. Results:The univariate and multivariate analyses showed that National Institute of Health stroke scale(NIHSS) score[odds ratio(OR)=1.530,95% confidence interval(CI)=1.229-1.904,P=0.000],Pittsburgh sleep quality index(PSQI) score(OR=1.249,95%CI=1.073 to 1.454,P=0.004),Visual Analogue Scale(VAS) score(OR=1.839,95%CI=1.111 to 3.045,P=0.018),income(OR=6.364,95%CI=1.670 to 24.249,P=0.007),and caregiver(OR=5.269,95%CI=1.384 to 20.058,P=0.015) were independent risk factors for depression in patients with stroke in rehabilitation stage. Conclusion:The patients with stroke who have higher NIHSS,PSQI,and VAS scores and a lower level of income and are taken care of by professional caregivers in rehabilitation phase are more likely to de-velop PSD.

    • Progress and challenges in gene therapy for Huntington's disease

      2019, 44(4):520.

      Abstract (1337) HTML (0) PDF 1.43 M (1103) Comment (0) Favorites

      Abstract:Huntington's disease is an autosomal dominant hereditary disease. Gene therapy is an effective means to control the progression of the disease and even to achieve radical cure. With the initial success of antisense oligonucleotide therapy for Huntington's disease, different strategies targeting genomic DNA or mRNA are being actively developed and improved, and clinical trials will be carried out in the near future. This review focuses on the current situation, further development, and clinical challenges of gene therapy for Huntington's disease.

    • Animal models of Huntington disease: Research advances and perspectives

      2019, 44(4):526.

      Abstract (1136) HTML (0) PDF 1.01 M (1611) Comment (0) Favorites

      Abstract:Huntington disease (HD) is a typical hereditary neurodegenerative disease caused by single HTT gene mutation, and a CAG repeat of >36 in the HTT gene may lead to HD. HD patients are characterized by the accumulation of variant proteins and neuronal death, with behavioral, cognitive, and mental disorders. Clear etiology makes HD an ideal model for the analysis of neurodegenerative diseases. This article briefly reviews the achievements in animal models of HD, in order to provide ideas for the research on such neurodegenerative diseases.

    • Advances in clinical research on early diagnosis and treatment of Huntington disease

      2019, 44(4):531.

      Abstract (1063) HTML (0) PDF 832.24 K (626) Comment (0) Favorites

      Abstract:Huntington disease (HD) is a neurodegenerative disease with autosomal dominant inheritance and is caused by abnormal amplification of CAG trinucleotide repeats in the Htt gene. Classical symptoms include dance-like symptoms and cognitive and mental disorders. Many fruitful studies have been conducted in recent years, and new diagnostic and therapeutic strategies are being developed. It is believed that in the future, more and more clinicians will become familiar with this disease and patients with this disease will obtain effective diagnosis and treatment.

    • Molecular biology advances in amyotrophic lateral sclerosis

      2019, 44(4):534.

      Abstract (1112) HTML (0) PDF 1.12 M (513) Comment (0) Favorites

      Abstract:The pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. Multiple genetic factors contribute to the degeneration of motor neurons and thus increase the susceptibility to ALS. With the rapid development of molecular biology techniques in recent years, there is an increasing diversity of research topics on ALS pathogenesis. Therefore, this article will illustrate the possible pathogenesis of ALS with reference to the latest achievements in the field of molecular biology and our own perspectives.

    • Research advances in clinical diagnosis and treatment of amyotrophic lateral sclerosis

      2019, 44(4):539.

      Abstract (3349) HTML (0) PDF 939.78 K (1002) Comment (0) Favorites

      Abstract:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which mainly involves the pyramidal tract, the brain stem, and spinal cord anterior horn motor neuron. Major clinical manifestations include progressive aggravation of muscle atrophy, weakness, and bulbar palsy, and patients may eventually die of respiratory failure. In addition to the motor symptoms of ALS, its non-motor symptoms have attracted more and more attention. At present, the diagnosis of ALS is mainly based on medical history, clinical manifestation, and electrophysiological results, and auxiliary examinations only help to exclude other diseases with similar clinical manifestations. The research advances in genetics and biomarkers provide an objective reference for early diagnosis of ALS, exploration of pathophysiological mechanism, and evaluation of disease progression and prognosis. Although existing drugs for ALS cannot effectively stop the progression of ALS, new treatments including gene modification and stem cell transplantation hold promise for clinical application in the treatment of ALS.

    • Research progress in pain management in amyotrophic lateral sclerosis

      2019, 44(4):543.

      Abstract (960) HTML (0) PDF 960.20 K (417) Comment (0) Favorites

      Abstract:In recent years, more and more attention has been paid to pain management in patients with amyotrophic lateral sclerosis. As a common non-motor symptom, pain affects the quality of life of patients severely. Pain is often neglected by clinicians in clinical practice, due to that it may be masked by the motor symptoms of amyotrophic lateral sclerosis. The pathogenesis of pain in amyotrophic lateral sclerosis is still unclear, which leads to little understanding of the nature, classification, and treatment of pain. This article describes the thinking and methods of pain management in amyotrophic lateral sclerosis by reviewing recent research results.

    • Significance of human brain banking and recent advances in China and foreign countries

      2019, 44(4):547.

      Abstract (2669) HTML (0) PDF 1.06 M (1306) Comment (0) Favorites

      Abstract:Human brain banks collect postmortem and resected human nervous tissue samples and data on diseases and lifestyle before death from donors and thus support the observation and research on healthy or diseased human brain tissue. The establishment of human brain banks has been taken seriously in Western developed countries, with the formation of large-scale brain banks focusing on clinical cohorts. Human brain banks promote the exploration of human brain morphology and function, neurodevelopment and aging, and pathogenesis and mechanism of various neurological and mental disorders, gradually reveal the mechanism of normal brain activities, and thus provide new directions for the prevention and treatment of nervous system diseases. Human brain banking needs to be promoted in China. This article introduces the significance of human brain banking and the basic information of human brain banks in foreign countries, as well as investigations and reflections of the current status of human brain banking in China.

Competent unitl:Chongqing Committee of Education

Organizer:Chongqing Medical University

Editorial Office:Editorial Department of Journal of Chongqing Medical University

Editor in chief:Huang Ailong

Editorial Director:Ran Minghui

International standard number:ISSN

Unified domestic issue:CN

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