Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxid...Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.展开更多
Mountainous regions are particularly sensitive to climate change. Seasonal and annual variations in climate already strongly influence the ecosystems in such areas. Temporal and spatial variations of temperature and p...Mountainous regions are particularly sensitive to climate change. Seasonal and annual variations in climate already strongly influence the ecosystems in such areas. Temporal and spatial variations of temperature and precipitation, for higher elevation site (Hailuogou Station) and lower elevation site (Moxi Station) within Hailuogou watershed which is located on the eastern slope of Mount Gongga, China, were analyzed to evaluate the extent and trend of climate change. Climate data were carefully checked and corrected for errors before being analyzed. The results of this work indicate that the measured climate data contain a wide magnitude of variations in temperature and precipitation in the mountainous region. The annual, minimal and maximal temperatures exhibit some increasing trends during the studied period. The results of this work show that slightly warming climate is mostly caused by increasing minimum temperature. Maximal precipitation mostly occurs in July and minimal precipitation mostly occurs in December. There exists a slightly declining trend of precipitation during 1988-2009. Precipitation exhibits an increasing trend with altitude, whereas the temperature has the reverse trend in the alpine area during studied period.展开更多
To the Editor:Amyloidosis is caused by the extracellular deposition of insoluble beta-pleated protein fibrils in tissues and is classified according to the constituent proteins.The cause of amyloidosis can be traced t...To the Editor:Amyloidosis is caused by the extracellular deposition of insoluble beta-pleated protein fibrils in tissues and is classified according to the constituent proteins.The cause of amyloidosis can be traced to more than 30 kinds of malfolded proteins,and accurate amyloid typing is crucial for appropriate therapy.[1]The pathological diagnosis is confirmed with positive Congo red(CR)staining under a light microscope and 7 to 12 nm branching fibrils under an electron microscope.Further identification of some amyloid precursor proteins can resort to immunofluorescence(IF)and immunochemistry(IHC);however,the accuracy depends on the selected antibodies to a large extent.Laser microdissection coupled with liquid chromatography-tandem mass spectrometry(LMD/MS)can identify these proteins without the restriction of IF and IHC,although exquisite equipment and skilled specialists are required.[2]This study aimed to establish LMD/MS analysis of renal biopsy tissue and compare it with IHC on diagnostic sensitivity.展开更多
Background and purpose Detection of atrial fibrillation(AF)after acute ischaemic stroke is pivotal for the timely initiation of anticoagulation to prevent recurrence.Besides heart rhythm monitoring,various blood bioma...Background and purpose Detection of atrial fibrillation(AF)after acute ischaemic stroke is pivotal for the timely initiation of anticoagulation to prevent recurrence.Besides heart rhythm monitoring,various blood biomarkers have been suggested as complimentary diagnostic tools for AF.We aimed to summarise data on the performance of cardiac natriuretic peptides for the diagnosis of covert AF after acute ischaemic stroke and to assess their potential clinical utility.Methods We searched PubMed and Embase for prospective studies reporting the performance of B-type natriuretic peptide(BNP)or N-terminal pro-BNP(NT-proBNP)for the diagnosis of covert AF after acute ischaemic stroke.Summary diagnostic performance measures were pooled using bivariate meta-analysis with a random-effect model.Results We included six studies focusing on BNP(n=1930)and three studies focusing on NT-proBNP(n=623).BNP had a sensitivity of 0.83(95% CI 0.64 to 0.93),a specificity of 0.74(0.67 to 0.81),a positive likelihood ratio of 3.2(2.6 to 4.0)and a negative likelihood ratio of 0.23(0.11 to 0.49).NT-proBNP had a sensitivity of 0.91(0.65 to 0.98),a specificity of 0.77(0.52 to 0.91),a positive likelihood ratio of 3.9(1.8 to 8.7)and a negative likelihood ratio of 0.12(0.03 to 0.48).Considering a pretest probability of 20%,BNP and NT-proBNP had post-test probabilities of 45%and 50%.Conclusions NT-proBNP has a better performance than BNP for the diagnosis of covert AF after acute ischaemic stroke.Both biomarkers have low post-test probabilities and may not be used as a stand-alone decision-making tool for the diagnosis of covert AF in patients with acute ischaemic stroke.However,they may be useful for a screening strategy aiming to select patients for long-term monitoring of the heart rhythm.展开更多
基金supported by the National Natural Science Foundation of China,No.82071442 (to LS)a grant from the Jilin Provincial Department of Finance,No.JLSWSRCZX2021-004 (to LS)。
文摘Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.
文摘Mountainous regions are particularly sensitive to climate change. Seasonal and annual variations in climate already strongly influence the ecosystems in such areas. Temporal and spatial variations of temperature and precipitation, for higher elevation site (Hailuogou Station) and lower elevation site (Moxi Station) within Hailuogou watershed which is located on the eastern slope of Mount Gongga, China, were analyzed to evaluate the extent and trend of climate change. Climate data were carefully checked and corrected for errors before being analyzed. The results of this work indicate that the measured climate data contain a wide magnitude of variations in temperature and precipitation in the mountainous region. The annual, minimal and maximal temperatures exhibit some increasing trends during the studied period. The results of this work show that slightly warming climate is mostly caused by increasing minimum temperature. Maximal precipitation mostly occurs in July and minimal precipitation mostly occurs in December. There exists a slightly declining trend of precipitation during 1988-2009. Precipitation exhibits an increasing trend with altitude, whereas the temperature has the reverse trend in the alpine area during studied period.
基金the National Key Research and Development Program of China(No.2016YFC0901500).
文摘To the Editor:Amyloidosis is caused by the extracellular deposition of insoluble beta-pleated protein fibrils in tissues and is classified according to the constituent proteins.The cause of amyloidosis can be traced to more than 30 kinds of malfolded proteins,and accurate amyloid typing is crucial for appropriate therapy.[1]The pathological diagnosis is confirmed with positive Congo red(CR)staining under a light microscope and 7 to 12 nm branching fibrils under an electron microscope.Further identification of some amyloid precursor proteins can resort to immunofluorescence(IF)and immunochemistry(IHC);however,the accuracy depends on the selected antibodies to a large extent.Laser microdissection coupled with liquid chromatography-tandem mass spectrometry(LMD/MS)can identify these proteins without the restriction of IF and IHC,although exquisite equipment and skilled specialists are required.[2]This study aimed to establish LMD/MS analysis of renal biopsy tissue and compare it with IHC on diagnostic sensitivity.
基金financially supported by the National Key Research and Development Program of China(2018YFA0704103)the National Natural Science Foundation of China(81971750 and 61821002)+1 种基金partially by the Natural Science Foundation of Jiangsu Province(BK20191266)the Jiangsu Province 333 High-level Talents Training Project。
文摘Background and purpose Detection of atrial fibrillation(AF)after acute ischaemic stroke is pivotal for the timely initiation of anticoagulation to prevent recurrence.Besides heart rhythm monitoring,various blood biomarkers have been suggested as complimentary diagnostic tools for AF.We aimed to summarise data on the performance of cardiac natriuretic peptides for the diagnosis of covert AF after acute ischaemic stroke and to assess their potential clinical utility.Methods We searched PubMed and Embase for prospective studies reporting the performance of B-type natriuretic peptide(BNP)or N-terminal pro-BNP(NT-proBNP)for the diagnosis of covert AF after acute ischaemic stroke.Summary diagnostic performance measures were pooled using bivariate meta-analysis with a random-effect model.Results We included six studies focusing on BNP(n=1930)and three studies focusing on NT-proBNP(n=623).BNP had a sensitivity of 0.83(95% CI 0.64 to 0.93),a specificity of 0.74(0.67 to 0.81),a positive likelihood ratio of 3.2(2.6 to 4.0)and a negative likelihood ratio of 0.23(0.11 to 0.49).NT-proBNP had a sensitivity of 0.91(0.65 to 0.98),a specificity of 0.77(0.52 to 0.91),a positive likelihood ratio of 3.9(1.8 to 8.7)and a negative likelihood ratio of 0.12(0.03 to 0.48).Considering a pretest probability of 20%,BNP and NT-proBNP had post-test probabilities of 45%and 50%.Conclusions NT-proBNP has a better performance than BNP for the diagnosis of covert AF after acute ischaemic stroke.Both biomarkers have low post-test probabilities and may not be used as a stand-alone decision-making tool for the diagnosis of covert AF in patients with acute ischaemic stroke.However,they may be useful for a screening strategy aiming to select patients for long-term monitoring of the heart rhythm.
