Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polariz...Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.展开更多
Background:Breast cancer is the most common cancer in women,and in advanced stages,it often metastasizes to the brain.However,research on the biological mechanisms of breast cancer brain metastasis and potential thera...Background:Breast cancer is the most common cancer in women,and in advanced stages,it often metastasizes to the brain.However,research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited.Methods:Differential gene expression analysis(DEGs)for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox.Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal.Thus,expression levels,variations,associations with HER2,biological processes,and pathways involv-ing SULF1 could be analyzed using UALCAN,cBioPortal,GEPIA2,and LinkedOmics databases.Moreover,the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP.Results:High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2.In the metastatic breast cancer population,SULF1 ranked top among the 16 DEGs with the highest mutation rate,reaching 11%,primarily due to amplification.KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the‘ECM-receptor interaction’gene set and negatively enriched in the‘Ribosome’gene set.Currently,docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high.Conclusions:This study,through bioinformatics analysis,unveiled SULF1 as a poten-tial target for treating breast cancer brain metastasis(BM).展开更多
Background:The continuing emergence of influenza virus has highlighted the value of public databases and related bioinformatic analysis tools in investigating transcriptomic change caused by different influenza virus ...Background:The continuing emergence of influenza virus has highlighted the value of public databases and related bioinformatic analysis tools in investigating transcriptomic change caused by different influenza virus infections in human and animal models.Methods:We collected a large amount of transcriptome research data related to influenza virus-i nfected human and animal models in public databases(GEO and ArrayExpress),and extracted and integrated array and metadata.The gene expression matrix was generated through strictly quality control,balance,standardization,batch correction,and gene annotation.We then analyzed gene expression in different species,virus,cells/tissues or after antibody/vaccine treatment and imported sample metadata and gene expression datasets into the database.Results:Overall,maintaining careful processing and quality control,we collected 8064 samples from 103 independent datasets,and constructed a comparative transcriptomics database of influenza virus named the Flu-CED database(Influenza comparative expression database,https://flu.com-med.org.cn/).Using integrated and processed transcriptomic data,we established a user-friendly website for realizing the integration,online retrieval,visualization,and exploration of gene expression of influenza virus infection in different species and the biological functions involved in differential genes.Flu-CED can quickly query single and multi-gene expression profiles,combining different experimental conditions for comparative transcriptome analysis,identifying differentially expressed genes(DEGs)between comparison groups,and conveniently finding DEGs.Conclusion:Flu-CED provides data resources and tools for analyzing gene expression in human and animal models infected with influenza virus that can deepen our understanding of the mechanisms underlying disease occurrence and development,and enable prediction of key genes or therapeutic targets that can be used for medical research.展开更多
Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the speci...Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs.展开更多
Background: With the aim of establishing the most comprehensive database of laboratory animal strains, the "laboratory animal strain resources database"(LasDB)was constructed as a searchable online database ...Background: With the aim of establishing the most comprehensive database of laboratory animal strains, the "laboratory animal strain resources database"(LasDB)was constructed as a searchable online database of all laboratory animal strains,stocks and mutant embryonic stem-cell lines available worldwide, including inbred,outbred, mutant and genetically engineered strains.Methods: MySQL database software was used to construct the LasDB, offering an easy-to-use interface.Results: To date, LasDB has a collection covering data for 21 596 mouse strains,2062 rat strains, 13 monkey strains, 2 hamster strains, 5 dog strains, 5 rabbit strains and more than 50 other laboratory animal strains. LasDB will be continually improved with regular updates of new laboratory animal strains from all over the world.Conclusion: To the best of our knowledge, this is the first database that attempts to systematically integrate all available laboratory animal strain data with the aim of supporting open usage and full resource sharing.展开更多
Background:Juvenile Localized Scleroderma(JLS)is a rare pediatric rheumatic disease characterized by inflammation and skin sclerosis.The side effect of consensus-recommended medications and the risk of disability pose...Background:Juvenile Localized Scleroderma(JLS)is a rare pediatric rheumatic disease characterized by inflammation and skin sclerosis.The side effect of consensus-recommended medications and the risk of disability posed challenges to the JLS treatment.We intend to demonstrate the potential of traditional Chinese medicine in treating JLS with skin ulcers and reducing the dose of glucocorticoid.Method:Here we report a case of a 13-year-old male with JLS who took oral methotrexate tablets of 10 mg/week and methylprednisolone of 6 mg/day for over six months without significant effect and suffered from skin ulcers on the dorsal feet one month after drug cessation.Subsequently,the patient was treated with integrated traditional Chinese and Western medicine of low-dose glucocorticosteroid,adjusted Shenqi Huoxue formula and Jinshe Xiaoyan formula,etc.Results:After integrated treatment,the patient’s dorsal feet ulcers healed and the skin sclerosis and hyperpigmentation improved significantly.Conclusions:This case report suggests that integrated traditional Chinese and Western medicine can be used as an effective treatment for JLS.展开更多
Various pathological mechanisms represent distinct therapeutic targets for cognitive disorders,but a balance between clearance and production is essential for maintaining the stability of the brain's internal envi...Various pathological mechanisms represent distinct therapeutic targets for cognitive disorders,but a balance between clearance and production is essential for maintaining the stability of the brain's internal environment.Thus,the glymphatic system may represent a common pathway by which to address cognitive disorders.Using the established model of the glymphatic system as our foundation,this review disentangles and analyzes the components of its clearance mechanism,including the initial inflow of cerebrospinal fluid,the mixing of cerebrospinal fluid with interstitial fluid,and the outflow of the mixed fluid and the clearance.Each section summarizes evidence from experimental animal models and human studies,highlighting the normal physiological properties of key structures alongside their pathological manifestations in cognitive disorders.The same pathologic manifestations of different cognitive disorders appearing in the glymphatic system and the same upstream influences are main points of interest of this review.We conclude this article by discussing new findings and outlining the limitations identified in current research progress.展开更多
Background:C1QL3 is widely expressed in the brain and is specifically produced by a subset of excitatory neurons.However,its function is still not clear.We established C1ql3-deficient rats to investigate the role of C...Background:C1QL3 is widely expressed in the brain and is specifically produced by a subset of excitatory neurons.However,its function is still not clear.We established C1ql3-deficient rats to investigate the role of C1QL3 in the brain.Methods:C1ql3 knockout(KO)rats were generated using CRISPR/Cas9.C1ql3 KO was determined by polymerase chain reaction(PCR),DNA sequencing,and western blot-ting.Microglia morphology and cytokine expression with or without lipopolysaccha-ride(LPS)stimulus were analyzed using immunohistochemistry and real-time PCR.The brain structure changes in KO rats were examined using magnetic resonance imaging.Neuronal architecture alteration was analyzed by performing Golgi staining.Behavior was evaluated using the open field test,Morris water maze test,and Y maze test.Results:C1ql3 KO significantly increased the number of ramified microglia and decreased the number of hypertrophic microglia,whereas C1ql3 KO did not in-fluence the expression of pro-inflammatory factors and anti-inflammatory factors except IL-10.C1ql3 KO brains had more amoeboid microglia types and higher Arg-1 expression compared with the WT rats after LPS stimulation.The brain weights and HPC sizes of C1ql3 KO rats did not differ from WT rats.C1ql3 KO damaged neuronal integrity including neuron dendritic arbors and spine density.C1ql3 KO rats demonstrated an increase in spontaneous activity and an impairment in short working memory.Conclusions:C1ql3 KO not only interrupts the neuronal integrity but also affects the microglial activation,resulting in hyperactive behavior and impaired short memory in rats,which highlights the role of C1QL3 in the regulation of structure and function of both neuronal and microglial cells.展开更多
Background:Asymptomatic coronary artery stenosis(ACAS)≥50%is common in patients with acute ischemic cerebrovascular disease(AICVD),which portends a poor cardiovascular and cerebrovascular prognosis.Identifying ACAS&g...Background:Asymptomatic coronary artery stenosis(ACAS)≥50%is common in patients with acute ischemic cerebrovascular disease(AICVD),which portends a poor cardiovascular and cerebrovascular prognosis.Identifying ACAS>50%early may optimize the clinical management and improve the outcomes of these high-risk AICVD patients.This study aimed to investigate whether aortic arch plaque(AAP),an early atherosclerotic manifestation of brain blood-supplying arteries,could be a predictor for ACAS>50%in AICVD.Methods:In this cross-sectional study,atherosclerosis of the coronary and brain blood-supplying arteries was simultaneously evaluated using one-step computed tomography angiography(CTA)in AICVD patients without coronary artery disease history.The patients were divided into ACAS≥50%and non-ACAS≥50%groups according to whether CTA showed stenosis≥50%in at least one coronary arterial segment.The AAP characteristics of CTA were depicted from aspects of thickness,extent,and complexity.Results:Among 118 analyzed patients with AICVD,29/118(24.6%)patients had ACAS≥50%,while AAPs were observed in 86/118(72.9%)patients.Increased AAP thickness per millimeter(adjusted odds ratio[OR]:1.56,95%confidence interval[CI]:1.18-2.05),severe-extent AAP(adjusted OR:13.66,95%CI:2.33-80.15),and presence of complex AAP(adjusted OR:7.27,95%CI:2.30-23.03)were associated with ACAS≥50%among patients with AICVD,independently of clinical demographics and cervicocephalic atherosclerotic stenosis.The combination of AAP thickness,extent,and complexity predicted ACAS≥50%with an area under the receiver-operating characteristic curve of 0.78(95%CI:0.70-0.85,P<0.001).All three AAP characteristics provided additional predictive power beyond cervical and intracranial atherosclerotic stenosis for ACAS≥50%in AICVD(all P<0.05).Conclusions:Thicker,severe-extent,and complex AAP were significant markers of the concomitant ACAS≥50%in AICVD,possibly superior to the indicative value of cervical and intracranial atherosclerotic stenosis.As an integral part of atherosclerosis of brain blood-supplying arteries,AAP should not be overlooked in predicting ACAS≥50%for patients with AICVD.展开更多
Atherosclerosis (AS) is a systemic chronic disease affecting both the coronary and cerebral arteries. Inflammation plays a key role in the initiation and progression of AS, and numerous inflammatory factors have been ...Atherosclerosis (AS) is a systemic chronic disease affecting both the coronary and cerebral arteries. Inflammation plays a key role in the initiation and progression of AS, and numerous inflammatory factors have been proposed as potential biomarkers. This article reviews recent research in studies on major circulating inflammatory biomarkers to identify surrogates that may reflect processes associated with AS development and the risk of AS-related vascular events, such as Von Willebrand factor, lectin-like oxidized low-density-lipoprotein receptor-1, soluble urokinase plasminogen activator receptor, regulated upon activation, normal T-cell expressed and secreted, and microparticles, which may provide new perspectives for clinical AS evaluation and risk stratification.展开更多
Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly swept through the worldwide,with more than 3 million confirmed cases.Until now,no vaccine...Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly swept through the worldwide,with more than 3 million confirmed cases.Until now,no vaccine or effective therapeutic measures are provided to prevent the SARS-CoV-2 infection.Existing medicines have some strong advantages on pharmacokinetics,known side effects,safety and dosing regimens.1 Although remdesivir and chloroquine could effectively inhibit the replication of SARS-CoV-2 in vitro,2 no medicine candidates have been evaluated in vivo by using animal models with SARS-CoV-2 infection.展开更多
基金CAMs innovation Fund for Medical Sciences,Grant/Award Number:2022-12M-CoV19-005National Key Projects,Grant/Award Number:2023YFF0724900 and 2021YFF0702802。
文摘Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.
基金Peking Union Medical College,Grant/Award Number:3332022182。
文摘Background:Breast cancer is the most common cancer in women,and in advanced stages,it often metastasizes to the brain.However,research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited.Methods:Differential gene expression analysis(DEGs)for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox.Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal.Thus,expression levels,variations,associations with HER2,biological processes,and pathways involv-ing SULF1 could be analyzed using UALCAN,cBioPortal,GEPIA2,and LinkedOmics databases.Moreover,the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP.Results:High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2.In the metastatic breast cancer population,SULF1 ranked top among the 16 DEGs with the highest mutation rate,reaching 11%,primarily due to amplification.KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the‘ECM-receptor interaction’gene set and negatively enriched in the‘Ribosome’gene set.Currently,docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high.Conclusions:This study,through bioinformatics analysis,unveiled SULF1 as a poten-tial target for treating breast cancer brain metastasis(BM).
基金Chinese Academy of Medical Sciences Initiative for Innovative MedicineGrant/Award Number:2021-I2M-1-035+3 种基金Beijing Municipal Natural Science FoundationGrant/Award Number:M21027National Key Research and Development Program of ChinaGrant/Award Number:2021YFF0702800。
文摘Background:The continuing emergence of influenza virus has highlighted the value of public databases and related bioinformatic analysis tools in investigating transcriptomic change caused by different influenza virus infections in human and animal models.Methods:We collected a large amount of transcriptome research data related to influenza virus-i nfected human and animal models in public databases(GEO and ArrayExpress),and extracted and integrated array and metadata.The gene expression matrix was generated through strictly quality control,balance,standardization,batch correction,and gene annotation.We then analyzed gene expression in different species,virus,cells/tissues or after antibody/vaccine treatment and imported sample metadata and gene expression datasets into the database.Results:Overall,maintaining careful processing and quality control,we collected 8064 samples from 103 independent datasets,and constructed a comparative transcriptomics database of influenza virus named the Flu-CED database(Influenza comparative expression database,https://flu.com-med.org.cn/).Using integrated and processed transcriptomic data,we established a user-friendly website for realizing the integration,online retrieval,visualization,and exploration of gene expression of influenza virus infection in different species and the biological functions involved in differential genes.Flu-CED can quickly query single and multi-gene expression profiles,combining different experimental conditions for comparative transcriptome analysis,identifying differentially expressed genes(DEGs)between comparison groups,and conveniently finding DEGs.Conclusion:Flu-CED provides data resources and tools for analyzing gene expression in human and animal models infected with influenza virus that can deepen our understanding of the mechanisms underlying disease occurrence and development,and enable prediction of key genes or therapeutic targets that can be used for medical research.
基金The present work was supported in part by the Beijing Natural Science Foundation(5212017)CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-1-015)National Natural Science Foundation(31872314 and 31970508).
文摘Background:Multiple mitochondrial dysfunction syndromes(MMDS)presents as complex mitochondrial damage,thus impairing a variety of metabolic pathways.Heart dysplasia has been reported in MMDS patients;however,the specific clinical symptoms and pathogenesis remain unclear.More urgently,there is a lack of an animal model to aid research.Therefore,we selected a reported MMDS causal gene,Isca1,and established an animal model of MMDS complicated with cardiac dysplasia.Methods:The myocardium-specific Isca1 knockout heterozygote(Isca1 HET)rat was obtained by crossing the Isca1 conditional knockout(Isca1 cKO)rat with theαmyosin heavy chain Cre(α-MHC-Cre)rat.Cardiac development characteristics were determined by ECG,blood pressure measurement,echocardiography and histopatho-logical analysis.The responsiveness to pathological stimuli were observed through adriamycin treatment.Mitochondria and metabolism disorder were determined by activity analysis of mitochondrial respiratory chain complex and ATP production in myocardium.Results:ISCA1 expression in myocardium exhibited a semizygous effect.Isca1 HET rats exhibited dilated cardiomyopathy characteristics,including thin-walled ventri-cles,larger chambers,cardiac dysfunction and myocardium fibrosis.Downregulated ISCA1 led to deteriorating cardiac pathological processes at the global and organiza-tional levels.Meanwhile,HET rats exhibited typical MMDS characteristics,including damaged mitochondrial morphology and enzyme activity for mitochondrial respira-tory chain complexesⅠ,ⅡandⅣ,and impaired ATP production.Conclusion:We have established a rat model of MMDS complicated with cardiomyopathy,it can also be used as model of myocardial energy metabolism dysfunction and mitochondrial cardiomyopathy.This model can be applied to the study of the mechanism of energy metabolism in cardiovascular diseases,as well as research and development of drugs.
基金the Central Research Institutes Basic Operating Grants,Grant/Award Number:DWS201512CAMS Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2016-I2M-2-006-03National Major Scientific and Technological Special Project for Key Infectious Diseases,Grant/Award Number:2017ZX10304402-001
文摘Background: With the aim of establishing the most comprehensive database of laboratory animal strains, the "laboratory animal strain resources database"(LasDB)was constructed as a searchable online database of all laboratory animal strains,stocks and mutant embryonic stem-cell lines available worldwide, including inbred,outbred, mutant and genetically engineered strains.Methods: MySQL database software was used to construct the LasDB, offering an easy-to-use interface.Results: To date, LasDB has a collection covering data for 21 596 mouse strains,2062 rat strains, 13 monkey strains, 2 hamster strains, 5 dog strains, 5 rabbit strains and more than 50 other laboratory animal strains. LasDB will be continually improved with regular updates of new laboratory animal strains from all over the world.Conclusion: To the best of our knowledge, this is the first database that attempts to systematically integrate all available laboratory animal strain data with the aim of supporting open usage and full resource sharing.
基金The essay is supported by Research Project of Shanghai Municipal Health Care Commission,No.20204Y0410We appreciate the patient and his parents for their cooperation and consent to disclose the case.We express our gratitude for the support from the members of the scientific innovation volunteer team of rare diseases in Shanghai TCM-Integrated School of clinical medicine,Shanghai University of Traditional Chinese Medicine.
文摘Background:Juvenile Localized Scleroderma(JLS)is a rare pediatric rheumatic disease characterized by inflammation and skin sclerosis.The side effect of consensus-recommended medications and the risk of disability posed challenges to the JLS treatment.We intend to demonstrate the potential of traditional Chinese medicine in treating JLS with skin ulcers and reducing the dose of glucocorticoid.Method:Here we report a case of a 13-year-old male with JLS who took oral methotrexate tablets of 10 mg/week and methylprednisolone of 6 mg/day for over six months without significant effect and suffered from skin ulcers on the dorsal feet one month after drug cessation.Subsequently,the patient was treated with integrated traditional Chinese and Western medicine of low-dose glucocorticosteroid,adjusted Shenqi Huoxue formula and Jinshe Xiaoyan formula,etc.Results:After integrated treatment,the patient’s dorsal feet ulcers healed and the skin sclerosis and hyperpigmentation improved significantly.Conclusions:This case report suggests that integrated traditional Chinese and Western medicine can be used as an effective treatment for JLS.
基金supported by Zhejiang Provincial Medical and Health Science and Technology Project,Nos.2022KY008(to JW),2023KY001(to JW),2023KY006(to QL)Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project,No.2023ZL220(to QL)。
文摘Various pathological mechanisms represent distinct therapeutic targets for cognitive disorders,but a balance between clearance and production is essential for maintaining the stability of the brain's internal environment.Thus,the glymphatic system may represent a common pathway by which to address cognitive disorders.Using the established model of the glymphatic system as our foundation,this review disentangles and analyzes the components of its clearance mechanism,including the initial inflow of cerebrospinal fluid,the mixing of cerebrospinal fluid with interstitial fluid,and the outflow of the mixed fluid and the clearance.Each section summarizes evidence from experimental animal models and human studies,highlighting the normal physiological properties of key structures alongside their pathological manifestations in cognitive disorders.The same pathologic manifestations of different cognitive disorders appearing in the glymphatic system and the same upstream influences are main points of interest of this review.We conclude this article by discussing new findings and outlining the limitations identified in current research progress.
基金The present work was supported by the National Natural Science Foundation(31970508)the National Key Research and Development Program of China(2022YFF0710702).
文摘Background:C1QL3 is widely expressed in the brain and is specifically produced by a subset of excitatory neurons.However,its function is still not clear.We established C1ql3-deficient rats to investigate the role of C1QL3 in the brain.Methods:C1ql3 knockout(KO)rats were generated using CRISPR/Cas9.C1ql3 KO was determined by polymerase chain reaction(PCR),DNA sequencing,and western blot-ting.Microglia morphology and cytokine expression with or without lipopolysaccha-ride(LPS)stimulus were analyzed using immunohistochemistry and real-time PCR.The brain structure changes in KO rats were examined using magnetic resonance imaging.Neuronal architecture alteration was analyzed by performing Golgi staining.Behavior was evaluated using the open field test,Morris water maze test,and Y maze test.Results:C1ql3 KO significantly increased the number of ramified microglia and decreased the number of hypertrophic microglia,whereas C1ql3 KO did not in-fluence the expression of pro-inflammatory factors and anti-inflammatory factors except IL-10.C1ql3 KO brains had more amoeboid microglia types and higher Arg-1 expression compared with the WT rats after LPS stimulation.The brain weights and HPC sizes of C1ql3 KO rats did not differ from WT rats.C1ql3 KO damaged neuronal integrity including neuron dendritic arbors and spine density.C1ql3 KO rats demonstrated an increase in spontaneous activity and an impairment in short working memory.Conclusions:C1ql3 KO not only interrupts the neuronal integrity but also affects the microglial activation,resulting in hyperactive behavior and impaired short memory in rats,which highlights the role of C1QL3 in the regulation of structure and function of both neuronal and microglial cells.
基金Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(No.ZYLX201706)Beijing Municipal Natural Science Foundation(No.7172093).
文摘Background:Asymptomatic coronary artery stenosis(ACAS)≥50%is common in patients with acute ischemic cerebrovascular disease(AICVD),which portends a poor cardiovascular and cerebrovascular prognosis.Identifying ACAS>50%early may optimize the clinical management and improve the outcomes of these high-risk AICVD patients.This study aimed to investigate whether aortic arch plaque(AAP),an early atherosclerotic manifestation of brain blood-supplying arteries,could be a predictor for ACAS>50%in AICVD.Methods:In this cross-sectional study,atherosclerosis of the coronary and brain blood-supplying arteries was simultaneously evaluated using one-step computed tomography angiography(CTA)in AICVD patients without coronary artery disease history.The patients were divided into ACAS≥50%and non-ACAS≥50%groups according to whether CTA showed stenosis≥50%in at least one coronary arterial segment.The AAP characteristics of CTA were depicted from aspects of thickness,extent,and complexity.Results:Among 118 analyzed patients with AICVD,29/118(24.6%)patients had ACAS≥50%,while AAPs were observed in 86/118(72.9%)patients.Increased AAP thickness per millimeter(adjusted odds ratio[OR]:1.56,95%confidence interval[CI]:1.18-2.05),severe-extent AAP(adjusted OR:13.66,95%CI:2.33-80.15),and presence of complex AAP(adjusted OR:7.27,95%CI:2.30-23.03)were associated with ACAS≥50%among patients with AICVD,independently of clinical demographics and cervicocephalic atherosclerotic stenosis.The combination of AAP thickness,extent,and complexity predicted ACAS≥50%with an area under the receiver-operating characteristic curve of 0.78(95%CI:0.70-0.85,P<0.001).All three AAP characteristics provided additional predictive power beyond cervical and intracranial atherosclerotic stenosis for ACAS≥50%in AICVD(all P<0.05).Conclusions:Thicker,severe-extent,and complex AAP were significant markers of the concomitant ACAS≥50%in AICVD,possibly superior to the indicative value of cervical and intracranial atherosclerotic stenosis.As an integral part of atherosclerosis of brain blood-supplying arteries,AAP should not be overlooked in predicting ACAS≥50%for patients with AICVD.
基金grants from Beijing Natural Science Foundation，'YangFan'Project of Beijing Municipal Administration of Hos-pitals
文摘Atherosclerosis (AS) is a systemic chronic disease affecting both the coronary and cerebral arteries. Inflammation plays a key role in the initiation and progression of AS, and numerous inflammatory factors have been proposed as potential biomarkers. This article reviews recent research in studies on major circulating inflammatory biomarkers to identify surrogates that may reflect processes associated with AS development and the risk of AS-related vascular events, such as Von Willebrand factor, lectin-like oxidized low-density-lipoprotein receptor-1, soluble urokinase plasminogen activator receptor, regulated upon activation, normal T-cell expressed and secreted, and microparticles, which may provide new perspectives for clinical AS evaluation and risk stratification.
基金supported by the National Key Research and Development Project of China(Grant No.2016YFD0500304)CAMS initiative for Innovative Medicine of China(Grant No.2016-I2M-2-006)+1 种基金National Mega projects of China for Major Infectious Diseases(Grant Nos.2017ZX10304402,2018ZX10301403)Fundamental Research Funds for CAMS of China(Grant No.2020HY320001).
文摘Dear Editor,Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),has rapidly swept through the worldwide,with more than 3 million confirmed cases.Until now,no vaccine or effective therapeutic measures are provided to prevent the SARS-CoV-2 infection.Existing medicines have some strong advantages on pharmacokinetics,known side effects,safety and dosing regimens.1 Although remdesivir and chloroquine could effectively inhibit the replication of SARS-CoV-2 in vitro,2 no medicine candidates have been evaluated in vivo by using animal models with SARS-CoV-2 infection.
