BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation...BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.展开更多
Activated nucleotide binding to the oligonucleotide receptor protein 3(NLRP3) inflammasome is possibly involved in the pathogenesis of Alzheimer's disease through oxidative stress and neurogenic inflammation. Low ...Activated nucleotide binding to the oligonucleotide receptor protein 3(NLRP3) inflammasome is possibly involved in the pathogenesis of Alzheimer's disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3(STAT3) gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NLRP3 inflammasome and STAT3 expression in oxidative stress,(1) SHSY5 Y cells were incubated with 1 mM H_2 O_2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca2+ chelator BAPATA-AM(0.1 mM) for 30 minutes as a control.(2) Western blot assay was used to analyze the expression of caspase-1, NLRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1β levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H_2 O_2 treatment activated NLRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H2 O2-induced activation of NLRP3 inflammasomes, caspase-1 expression, interleukin-1β expression and apoptosis in SHSY5 Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NLRP3, which may not depend on the Ca2+ signaling pathway.展开更多
Neurological abnormalities identified via neuroimaging are common in patients with Alzheimer’s disease.However,it is not yet possible to easily detect these abnormalities using head computed tomography in the early s...Neurological abnormalities identified via neuroimaging are common in patients with Alzheimer’s disease.However,it is not yet possible to easily detect these abnormalities using head computed tomography in the early stages of the disease.In this review,we evaluated the ways in which modern imaging techniques such as positron emission computed tomography,single photon emission tomography,magnetic resonance spectrum imaging,structural magnetic resonance imaging,magnetic resonance diffusion tensor imaging,magnetic resonance perfusion weighted imaging,magnetic resonance sensitive weighted imaging,and functional magnetic resonance imaging have revealed specific changes not only in brain structure,but also in brain function in Alzheimer’s disease patients.The reviewed literature indicated that decreased fluorodeoxyglucose metabolism in the temporal and parietal lobes of Alzheimer’s disease patients is frequently observed via positron emission computed tomography.Furthermore,patients with Alzheimer’s disease often show a decreased N-acetylaspartic acid/creatine ratio and an increased myoinositol/creatine ratio revealed via magnetic resonance imaging.Atrophy of the entorhinal cortex,hippocampus,and posterior cingulate gyrus can be detected early using structural magnetic resonance imaging.Magnetic resonance sensitive weighted imaging can show small bleeds and abnormal iron metabolism.Task-related functional magnetic resonance imaging can display brain function activity through cerebral blood oxygenation.Resting functional magnetic resonance imaging can display the functional connection between brain neural networks.These are helpful for the differential diagnosis and experimental study of Alzheimer’s disease,and are valuable for exploring the pathogenesis of Alzheimer’s disease.展开更多
基金Supported by the National Natural Science Foundation of China,No.3206080019 and No.32060182Science and Technology Support Plan of Guizhou Province in China,No.[2020]4Y129Qiannan Prefecture Science and Technology Plan Project,No.[2022]01.
文摘BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social problems.The quality of life and prognosis of AD patients have attracted much attention.The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important.AIM To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in patients.METHODS A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020.Collect cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other data.Multivariate logistic regression analysis was used to determine independent prog-nostic factors.the modified Rankin scale(mRS)was used to determine whether the prognosis was good.The correlation between drug treatment and prognostic mRS score was tested by the rank sum test.RESULTS Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD patients.Multivariate logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of AD.The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD.It is recommended that the proportion of T lymphocytes<55%is used as the cut-off threshold for predicting the poor prog-nosis of AD.The early and continuous drug treatment is associated with a good prognosis.
基金supported by Department of Science and Technology in Guizhou Province of China,No.Basic [2016]1131(to QianKe-He to HB)+2 种基金Department of Health and Family Planning Commission in Guizhou Province of China,No.2015-326(to HB)Less Developed Regions of the National Natural Science Foundation of China,No.81560482the Research Foundation for Creative Research Groups of Education Bureau of Guizhou Province of China,No.KY[2016]033(to QFZ)
文摘Activated nucleotide binding to the oligonucleotide receptor protein 3(NLRP3) inflammasome is possibly involved in the pathogenesis of Alzheimer's disease through oxidative stress and neurogenic inflammation. Low expression of the signal transducer and activator of transcription 3(STAT3) gene may promote the occurrence of neurodegenerative diseases to some extent. To clarify the roles of the NLRP3 inflammasome and STAT3 expression in oxidative stress,(1) SHSY5 Y cells were incubated with 1 mM H_2 O_2 to induce oxidative stress injury, and the expression of human-cell-specific signal transduction, STAT3-shRNA silencing signal transduction and STAT3 were detected. Cells were pretreated with Ca2+ chelator BAPATA-AM(0.1 mM) for 30 minutes as a control.(2) Western blot assay was used to analyze the expression of caspase-1, NLRP3, signal transduction and STAT3. Enzyme-linked immunosorbent assay was used to analyze interleukin-1β levels. Flow cytometry was carried out to calculate the number of apoptotic cells. We found that H_2 O_2 treatment activated NLRP3 inflammasomes and decreased phosphorylation of signal transduction and STAT3 serine 727. BAPTA-AM pretreatment abolished the H2 O2-induced activation of NLRP3 inflammasomes, caspase-1 expression, interleukin-1β expression and apoptosis in SHSY5 Y cells, and had no effect in cells with downregulated STAT3 expression by RNAi. The findings suggest that downregulation of signal transduction and STAT3 expression may enhance the oxidative stress mediated by NLRP3, which may not depend on the Ca2+ signaling pathway.
基金This work was supported by the Science and Technology Support Plan of Guizhou Province of China,No.QianKeHe-Zhicheng[2020]4Y129(to HB)the Scientific Research Foundation of Guizhou Health Committee of China,No.gzwkj2017-1-022(to HB)the Scientific Research Project of Guizhou Traditional Chinese Medicine Bureau of China,No.QZYY-2018-044(to HB).
文摘Neurological abnormalities identified via neuroimaging are common in patients with Alzheimer’s disease.However,it is not yet possible to easily detect these abnormalities using head computed tomography in the early stages of the disease.In this review,we evaluated the ways in which modern imaging techniques such as positron emission computed tomography,single photon emission tomography,magnetic resonance spectrum imaging,structural magnetic resonance imaging,magnetic resonance diffusion tensor imaging,magnetic resonance perfusion weighted imaging,magnetic resonance sensitive weighted imaging,and functional magnetic resonance imaging have revealed specific changes not only in brain structure,but also in brain function in Alzheimer’s disease patients.The reviewed literature indicated that decreased fluorodeoxyglucose metabolism in the temporal and parietal lobes of Alzheimer’s disease patients is frequently observed via positron emission computed tomography.Furthermore,patients with Alzheimer’s disease often show a decreased N-acetylaspartic acid/creatine ratio and an increased myoinositol/creatine ratio revealed via magnetic resonance imaging.Atrophy of the entorhinal cortex,hippocampus,and posterior cingulate gyrus can be detected early using structural magnetic resonance imaging.Magnetic resonance sensitive weighted imaging can show small bleeds and abnormal iron metabolism.Task-related functional magnetic resonance imaging can display brain function activity through cerebral blood oxygenation.Resting functional magnetic resonance imaging can display the functional connection between brain neural networks.These are helpful for the differential diagnosis and experimental study of Alzheimer’s disease,and are valuable for exploring the pathogenesis of Alzheimer’s disease.
