目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例...目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例)和对照组(未继发AE,165例)。多因素Logistic回归分析HSV感染患者继发AE的独立影响因素。Spearman法分析脑脊液中Cys-C、MMP-9与S100B水平的相关性。受试者工作特征(ROC)曲线分析S100B、Cys-C、MMP-9对AE的预测价值。构建风险预测模型并进行评价。结果:多因素Logistic回归分析显示,MRI异常、脑脊液S100B、MMP-9升高、EEG异常是HSV感染患者继发AE的独立危险因素,脑脊液Cys-C是其保护因素(P<0.05)。Spearman分析显示,HSV感染患者Cys-C浓度与S100B水平呈负相关(r=-0.83,P<0.05),MMP-9浓度与S100B水平呈正相关(r=0.88,P<0.05)。构建的联合预测因子pre1诊断HSV患者继发AE的AUC明显大于S100B、Cys-C、MMP-9单独预测的AUC(0.876 vs 0.827、0.787、0.750)。构建的风险预测模型具有良好的区分度和一致性。结论:脑脊液中S100B、Cys-C、MMP-9水平均可对HSV感染患者诱发AE的可能性进行有效预测,且三项指标联合预测价值最大,其次是S100B蛋白、Cys-C、MMP-9。展开更多
Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosi...Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.展开更多
Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic pancreatitis.The centralis...Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic pancreatitis.The centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved outcomes.In this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services.Type 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and outcome.Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period.The incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe pancreatitis.Early involvement of a specialist diabetes team is essential to ensure a holistic management.In the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve outcomes.While various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement.The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined,a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis.Therefore,pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams.With the ongoing accumulation of evidence,it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.展开更多
Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still un...Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway.展开更多
目的探讨S100b联合CRP在诊断早产儿脑损伤(Brain injury in premature infants,BIPI)中的临床效能。方法选择2022年1月—2024年1月于本院儿科确诊的125例BIPI患儿作为BIPI组,另选择同期收治的85例非BIPI早产儿作为对照组。根据BIPI患儿...目的探讨S100b联合CRP在诊断早产儿脑损伤(Brain injury in premature infants,BIPI)中的临床效能。方法选择2022年1月—2024年1月于本院儿科确诊的125例BIPI患儿作为BIPI组,另选择同期收治的85例非BIPI早产儿作为对照组。根据BIPI患儿病情严重程度分为轻度BIPI组和重度BIPI组两组亚组。收集所有研究对象的临床资料并检测血清中S100b联合CRP表达水平。Logistic回归分析发生BIPI的危险因素,S100b联合CRP在诊断BIPI的临床效能采用ROC曲线分析。结果对照组、轻度BIPI组和重度BIPI组三组间S100b、CRP表达水平存在统计学差异(P<0.05)。与对照组相比,轻度和重度BIPI组S100b、CRP表达水平均明显升高(P<0.05);与轻度BIPI组相比,重度BIPI组S100b、CRP表达水平均明显升高(P<0.05)。与对照组相比,宫内窘迫、出生后窒息、有创机械通气、新生儿呼吸窘迫综合征发生率及血清中S100b、CRP表达水平在BIPI组中明显升高(P<0.05)。Logistic回归分析结果显示,有创机械通气(OR=1.432)、新生儿呼吸窘迫综合征(OR=2.543)、S100b(OR=3.782)和CRP表达(OR=3.449)是发生BIPI的危险因素。S100b及CRP在诊断BIPI的曲线下面积分别为0.895和0.812,S100b联合CRP在诊断BIPI的曲线下面积为0.931,诊断敏感度和特异度分别为97.43%和92.25%。结论BIPI患儿外周血中S100b和CRP表达水平显著升高,S100b联合CRP在诊断BIPI中具有显著的临床价值。展开更多
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A...In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.展开更多
In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotr...In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.展开更多
目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学...目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学特征。方法选取2021年12月首都医科大学附属北京同仁医院来自同一家庭的CADASIL患者,对所有患者进行NOTCH3基因测序,回顾性分析患者的临床表现和头颅影像学特征。复习既往文献报道的导致同一位置氨基酸改变的其他突变类型的临床及影像学特征。结果4名家庭成员中,包括先证者(46岁,女)及其两个姐姐(分别为48岁和50岁)和女儿(18岁)。先证者及其父亲、两个姐姐都有偏头痛病史,其中大姐有记忆力减退;先证者患有脑梗死及伴有视觉先兆的偏头痛;先证者女儿体健;先证者父亲因脑梗死去世。4名家庭成员均存在C260S位点的NOTCH3基因突变。既往文献无此位点突变的报道,先证者头颅MRI示右侧脑桥亚急性梗死,颞叶、脑室周围及脑干异常高信号改变,其大姐脑桥可见腔隙性梗死灶。结论NOTCH3基因第5外显子c.778T>A(p.C260S)的罕见突变导致的CADASIL发病时间早,早期会出现认知障碍。合并偏头痛的脑干梗死患者,需警惕CADASIL的可能。展开更多
文摘目的:探究单纯疱疹病毒(HSV)感染后脑脊液(CSF)中S100B、Cys-C、MMP-9水平对自身免疫性脑炎(AE)的预测价值。方法:选取2016年1月至2021年3月河北中石油中心医院收治的200例HSV感染患者为研究对象,根据是否继发AE分为研究组(继发AE,35例)和对照组(未继发AE,165例)。多因素Logistic回归分析HSV感染患者继发AE的独立影响因素。Spearman法分析脑脊液中Cys-C、MMP-9与S100B水平的相关性。受试者工作特征(ROC)曲线分析S100B、Cys-C、MMP-9对AE的预测价值。构建风险预测模型并进行评价。结果:多因素Logistic回归分析显示,MRI异常、脑脊液S100B、MMP-9升高、EEG异常是HSV感染患者继发AE的独立危险因素,脑脊液Cys-C是其保护因素(P<0.05)。Spearman分析显示,HSV感染患者Cys-C浓度与S100B水平呈负相关(r=-0.83,P<0.05),MMP-9浓度与S100B水平呈正相关(r=0.88,P<0.05)。构建的联合预测因子pre1诊断HSV患者继发AE的AUC明显大于S100B、Cys-C、MMP-9单独预测的AUC(0.876 vs 0.827、0.787、0.750)。构建的风险预测模型具有良好的区分度和一致性。结论:脑脊液中S100B、Cys-C、MMP-9水平均可对HSV感染患者诱发AE的可能性进行有效预测,且三项指标联合预测价值最大,其次是S100B蛋白、Cys-C、MMP-9。
基金supported by Jiangsu Provincial Medical Key Discipline,No.ZDXK202217(to CFL)Jiangsu Planned Projects for Postdoctoral Research Funds,No.1601056C(to SL).
文摘Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.
文摘Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic pancreatitis.The centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved outcomes.In this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services.Type 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and outcome.Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period.The incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe pancreatitis.Early involvement of a specialist diabetes team is essential to ensure a holistic management.In the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve outcomes.While various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement.The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined,a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis.Therefore,pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams.With the ongoing accumulation of evidence,it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.
基金grants from the National Natural Science Foundation of China(82274454).
文摘Background:Ziwan and Taoren(ZT)is a classic medicine pair in the formula of Mai Dong Di Shao Decoction,has been used to treat primary Sjogren’s syndrome(pSS)for more than 20 years.But its action mechanism is still unknown.This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS.Methods:Firstly,the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis.Secondly,the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques.Finally,efficacy and mechanism were conducted through in vivo experiments,such as water intake,spleen index,hematoxylin-eosin staining pathological changes,ELISA,Western Blot analysis,and immunofluorescence staining.Results:Nine active compounds were extracted from network pharmacology,including quercitrin,luteolin,kaempferol,β-sitosterol,isorhamnetin,galangin,hederagenin,diosmetin and gibberellin 7.Seven disease targets were identified:RELA,TP53,AKT1,interleukin(IL)6,MAPK1,ESR1,IL10;with RELA being the most core target.KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process.preliminary results of molecular docking showed that ZT’s active compounds bind well to the RELA(p65)receptor.In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice.The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased,while levels of inflammatory factors such as tumor necrosis factor-α,IL-6,and IL-1βalong with protein expressions including toll-like receptor4,p-p65 and p-IKKα/βin NF-κB pathway were reduced.Conclusions:The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS,potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway.
文摘目的探讨S100b联合CRP在诊断早产儿脑损伤(Brain injury in premature infants,BIPI)中的临床效能。方法选择2022年1月—2024年1月于本院儿科确诊的125例BIPI患儿作为BIPI组,另选择同期收治的85例非BIPI早产儿作为对照组。根据BIPI患儿病情严重程度分为轻度BIPI组和重度BIPI组两组亚组。收集所有研究对象的临床资料并检测血清中S100b联合CRP表达水平。Logistic回归分析发生BIPI的危险因素,S100b联合CRP在诊断BIPI的临床效能采用ROC曲线分析。结果对照组、轻度BIPI组和重度BIPI组三组间S100b、CRP表达水平存在统计学差异(P<0.05)。与对照组相比,轻度和重度BIPI组S100b、CRP表达水平均明显升高(P<0.05);与轻度BIPI组相比,重度BIPI组S100b、CRP表达水平均明显升高(P<0.05)。与对照组相比,宫内窘迫、出生后窒息、有创机械通气、新生儿呼吸窘迫综合征发生率及血清中S100b、CRP表达水平在BIPI组中明显升高(P<0.05)。Logistic回归分析结果显示,有创机械通气(OR=1.432)、新生儿呼吸窘迫综合征(OR=2.543)、S100b(OR=3.782)和CRP表达(OR=3.449)是发生BIPI的危险因素。S100b及CRP在诊断BIPI的曲线下面积分别为0.895和0.812,S100b联合CRP在诊断BIPI的曲线下面积为0.931,诊断敏感度和特异度分别为97.43%和92.25%。结论BIPI患儿外周血中S100b和CRP表达水平显著升高,S100b联合CRP在诊断BIPI中具有显著的临床价值。
基金supported by STI2030-Major Projects,No.2021ZD 0201801(to JG)Shanxi Province Basic Research Program,No.20210302123429(to QS).
文摘In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.
文摘In this editorial,we comment on the article by Wang et al.This manuscript explores the potential synergistic effects of combining zanubrutinib,a novel oral inhibitor of Bruton’s tyrosine kinase,with high-dose methotrexate(HD-MTX)as a therapeutic intervention for primary central nervous system lymphoma(PCNSL).The study involves a retrospective analysis of 19 PCNSL patients,highlighting clinicopathological characteristics,treatment outcomes,and genomic biomarkers.The results indicate the combination’s good tolerance and strong antitumor activity,with an 84.2%overall response rate.The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL,particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B.Furthermore,the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring.In essence,the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL.The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes.While the findings suggest promise,the study’s limitations should be considered,and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.
文摘目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学特征。方法选取2021年12月首都医科大学附属北京同仁医院来自同一家庭的CADASIL患者,对所有患者进行NOTCH3基因测序,回顾性分析患者的临床表现和头颅影像学特征。复习既往文献报道的导致同一位置氨基酸改变的其他突变类型的临床及影像学特征。结果4名家庭成员中,包括先证者(46岁,女)及其两个姐姐(分别为48岁和50岁)和女儿(18岁)。先证者及其父亲、两个姐姐都有偏头痛病史,其中大姐有记忆力减退;先证者患有脑梗死及伴有视觉先兆的偏头痛;先证者女儿体健;先证者父亲因脑梗死去世。4名家庭成员均存在C260S位点的NOTCH3基因突变。既往文献无此位点突变的报道,先证者头颅MRI示右侧脑桥亚急性梗死,颞叶、脑室周围及脑干异常高信号改变,其大姐脑桥可见腔隙性梗死灶。结论NOTCH3基因第5外显子c.778T>A(p.C260S)的罕见突变导致的CADASIL发病时间早,早期会出现认知障碍。合并偏头痛的脑干梗死患者,需警惕CADASIL的可能。