Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined ex...Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.展开更多
When patients initially present with atrial fibrillation along with an enlarged heart and heart failure, followed by atrioventricular block, it's essential to consider genetic factors.^([1])Genetic testing can off...When patients initially present with atrial fibrillation along with an enlarged heart and heart failure, followed by atrioventricular block, it's essential to consider genetic factors.^([1])Genetic testing can offer crucial diagnostic evidence, aiding in prognosis assessment and the adoption of appropriate treatment strategies.展开更多
Objectives:Distal segment aortic enlargement(DSAE)is a common complication that influences the long-term prognosis of type B aortic dissection(TBAD)after thoracic endovascular aortic repair(TEVAR).In this study,a mult...Objectives:Distal segment aortic enlargement(DSAE)is a common complication that influences the long-term prognosis of type B aortic dissection(TBAD)after thoracic endovascular aortic repair(TEVAR).In this study,a multivariate analysis was performed to find potential factors predictive of DSAE.Methods:A single-center retrospective study was performed from 1999 to 2016.Included in the study were complicated TBAD patients who underwent TEVAR with uncovered residual tears.Based on the diameter of the distal segment of the uncovered aorta,we assigned patients to an enlargement group and a non-enlargement group.Data extracted from the medical records included demographic and clinical characteristics and followup computed tomography angiography data.The primary endpoints were the all-cause mortality and the presumably aortic-related events that required reintervention during the follow-up period.Results:For the 333 patients,all-cause mortality was 38(11.41%),and 76(22.82%)patients underwent reintervention.A total of 70(21.02%)patients experienced DSAE,among them were 2 patients who died of aortic rupture and 58 patients who accepted reintervention.Multivariate analysis reviewed independent risk factors of postoperative DSAE,including current smoking,the residual length of the patent false lumen,the postoperative number of dissection tears in the thoracic aorta and type III aortic arch;as well as protective factors,including the application of a restrictive bare stent(RBS),the length of covered stent in the descending thoracic aorta,and the distance from the residual first tear to the left subclavian artery(LSA).Conclusion:DSAE after TEVAR for patients with a complicated TBAD can be influenced by their current smoking habit,the residual length of patent false lumen,the postoperative number of dissection tears in the thoracic aorta and the aortic arch type.Meanwhile,RBS usage,the length of the covered stent in the descending thoracic aorta and the distance from the residual first tear to the LSA could have positive effect on the prognosis.展开更多
The inhibition of 5-a reductase type 2(SRD5A2)by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement(BPE).Certain BPE patients showing no SRD5A2 protein e...The inhibition of 5-a reductase type 2(SRD5A2)by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement(BPE).Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy.Our previous work showed that methylated cytosine-phosphate-guanine(CpG)islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression.Here,we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein(scored 0-100)occurred in 10.0%(4/40)of benign adult prostates.We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1(DNMT1)expression.In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment,and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2T-deoxycytidine(5-Aza-CdR)or N-phthalyl-L-tryptophan(RG108).Furthermore,we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis.Ten methylated CpG dinucleotides,including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon,were found in a CpG island located from-400 bp to+600 bp in SRD5A2,which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression.Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2,which may partially account for the resistance to finasteride observed in certain BPE patients.展开更多
BACKGROUND：Continuous hemorrhage or hematoma enlargement often occurs following cerebral hemorrhage attacks. OBJECTIVE： To retrospectively analyze the influential factors for hematoma enlargement in patients with hy...BACKGROUND：Continuous hemorrhage or hematoma enlargement often occurs following cerebral hemorrhage attacks. OBJECTIVE： To retrospectively analyze the influential factors for hematoma enlargement in patients with hypertensive cerebral hemorrhage prior to minimally invasive surgery. DESIGN, TIME AND SETTING： A comparative analysis of 90 patients with cerebral hemorrhage undergoing minimally invasive surgery at the Department of Neurology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology between April 2005 and February 2007. PARTICIPANTS： Fifty-eight males and thirty-one females aged （52.7 ± 5.23） years （range, 28-73 years）. METHODS： Cranial CT was performed twice to objectively identify hematoma enlargement. Patients with hematoma enlargement prior to surgery were selected as the observation group （n = 30）, and those with no obvious hematoma changes served as the control group （n = 60）. Following cranial CT localization, the two groups underwent minimally invasive hematoma aspiration and drainage, according to Standardized Treatment Guidelines for Micro-invasive Aspiration and Drainage of Intracranial Hematoma. MAIN OUTCOME MEASURES： Hemorrhage site, coagulation function, diabetes history, and clinical symptoms. RESULTS： There were no significant differences in hemorrhage sites between the two groups （χ2 = 2.262, P 〉 0.05）. The percent of intemperance patients in the observation group was significantly larger than the control group （χ2 = 6.923, P 〈 0.01）. No significant differences in terms of percent of coagulation dysfunction or diabetes were determined between the two groups （χ2 = 0.03, 0.08, P 〉 0.05）. The percent of patients with clinical deterioration was significantly higher in the observation group, compared to the control group （χ2 = 25.57, P 〈 0.01）. CONCLUSION： Intemperance and preoperative clinical deterioration may increase incidence of hematoma enlargement prior to minimally invasive surgery in patients with hypertensive cerebral hemorrhage.展开更多
AIM:To compare the difference between tumorinduced lymph node enlargement and inflammation-induced lymph node enlargement by contrast-enhanced ultrasonography and pathological findings. METHODS:A model of tumor-induce...AIM:To compare the difference between tumorinduced lymph node enlargement and inflammation-induced lymph node enlargement by contrast-enhanced ultrasonography and pathological findings. METHODS:A model of tumor-induced lymph node metastasis was prepared by embedding a VX2 tumor into the hind paws of white rabbits.A model of inflammation-induced enlargement was prepared by injecting a suspension of Escherichia coli into separate hind paws of white rabbits.Then,a solution of SonazoidTM(GE Healthcare,Oslo,Norway)was injected subcutaneously in the proximity of the lesion followed by contrast-enhanced ultrasonography of the enlarged popliteal lymph nodes. RESULTS:In the contrast-enhanced ultrasonography of the tumor-induced metastasis model,the sentinel lymph node was imaged.An area of filling defect was observed in that enlarged lymph node.In the histology examination,the area of filling defect corresponded to the metastatic lesion of the tumor.Contrast-enhanced ultrasonography of the model on inflammation-induced lymph node enlargement,and that of the acute inflam-mation model performed 3-7 d later,revealed dense staining that was comparatively uniform.The pathological findings showed acute lymphadenitis mainly due to infiltration of inflammatory cells.Contrast-enhanced ultrasonography that was performed 28 d post-infection in the acute inflammation model showed speckled staining.Inflammation-induced cell infiltration and fiberization,which are findings of chronic lymphadenitis, were seen in the pathological findings. CONCLUSION:Sentinel lymph node imaging was made possible by subcutaneous injection of SonazoidTM.Contrast-enhanced ultrasonography was suggested to be useful in differentiating tumor-induced enlargement and inflammation-induced enlargement of lymph nodes.展开更多
Enlarged vestibular aqueduct(EVA), the most frequent identifiable cause of congenital hearing loss, is evaluated with high-definition multidetector CT in the axial plane. Our purpose was to determine which reformatted...Enlarged vestibular aqueduct(EVA), the most frequent identifiable cause of congenital hearing loss, is evaluated with high-definition multidetector CT in the axial plane. Our purpose was to determine which reformatted CT measurements are most reproducible. Seven multiplanar reformatted images were created for each of the 64 temporal bones in patients with EVA. Intraclass correlation coefficients(ICC) were used to assess inter-observer variability, and both linear regression and ROC analyses were used to compare the measurements with severity of hearing loss, as assessed by pure tone audiometry. All seven measurements had excellent inter-observer variability, with average-measure ICC ranging from 0.92 to 0.98. There was no statistically significant correlation between the radiologic degree of aqueduct enlargement and severity of hearing loss using any of the seven measurements; ROC analyses revealed areas under the curves ranging from 0.57 to 0.73. Optimal accuracy was obtained with a threshold of 1.75 mm as measured at the aqueductal aperture in the P€oschl plane, with sensitivity of 0.75 and specificity of0.63. Although the radiologic measurement may not serve as a reliable tool for assessing severity of EVA, P€oschl plane reformatting has proven to be better than conventional axial acquisition plane for identifying patients with clinically significant hearing loss.展开更多
基金supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)+1 种基金the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
文摘Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
基金Military Healthcare Special Scientific Research Project(25BJZ31, awarded to SHI XM)。
文摘When patients initially present with atrial fibrillation along with an enlarged heart and heart failure, followed by atrioventricular block, it's essential to consider genetic factors.^([1])Genetic testing can offer crucial diagnostic evidence, aiding in prognosis assessment and the adoption of appropriate treatment strategies.
基金supported by the National Nature Science Foundation of China[grant number 81800403].
文摘Objectives:Distal segment aortic enlargement(DSAE)is a common complication that influences the long-term prognosis of type B aortic dissection(TBAD)after thoracic endovascular aortic repair(TEVAR).In this study,a multivariate analysis was performed to find potential factors predictive of DSAE.Methods:A single-center retrospective study was performed from 1999 to 2016.Included in the study were complicated TBAD patients who underwent TEVAR with uncovered residual tears.Based on the diameter of the distal segment of the uncovered aorta,we assigned patients to an enlargement group and a non-enlargement group.Data extracted from the medical records included demographic and clinical characteristics and followup computed tomography angiography data.The primary endpoints were the all-cause mortality and the presumably aortic-related events that required reintervention during the follow-up period.Results:For the 333 patients,all-cause mortality was 38(11.41%),and 76(22.82%)patients underwent reintervention.A total of 70(21.02%)patients experienced DSAE,among them were 2 patients who died of aortic rupture and 58 patients who accepted reintervention.Multivariate analysis reviewed independent risk factors of postoperative DSAE,including current smoking,the residual length of the patent false lumen,the postoperative number of dissection tears in the thoracic aorta and type III aortic arch;as well as protective factors,including the application of a restrictive bare stent(RBS),the length of covered stent in the descending thoracic aorta,and the distance from the residual first tear to the left subclavian artery(LSA).Conclusion:DSAE after TEVAR for patients with a complicated TBAD can be influenced by their current smoking habit,the residual length of patent false lumen,the postoperative number of dissection tears in the thoracic aorta and the aortic arch type.Meanwhile,RBS usage,the length of the covered stent in the descending thoracic aorta and the distance from the residual first tear to the LSA could have positive effect on the prognosis.
基金the National Natural Science Foundation of China(No.81770754)the Beiing Natural Science Foundation(No.7172081)at Beijing Chaoyang Hospital,Capital Medical University,through funding provided to YNN.
文摘The inhibition of 5-a reductase type 2(SRD5A2)by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement(BPE).Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy.Our previous work showed that methylated cytosine-phosphate-guanine(CpG)islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression.Here,we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein(scored 0-100)occurred in 10.0%(4/40)of benign adult prostates.We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1(DNMT1)expression.In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment,and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2T-deoxycytidine(5-Aza-CdR)or N-phthalyl-L-tryptophan(RG108).Furthermore,we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis.Ten methylated CpG dinucleotides,including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon,were found in a CpG island located from-400 bp to+600 bp in SRD5A2,which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression.Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2,which may partially account for the resistance to finasteride observed in certain BPE patients.
文摘BACKGROUND：Continuous hemorrhage or hematoma enlargement often occurs following cerebral hemorrhage attacks. OBJECTIVE： To retrospectively analyze the influential factors for hematoma enlargement in patients with hypertensive cerebral hemorrhage prior to minimally invasive surgery. DESIGN, TIME AND SETTING： A comparative analysis of 90 patients with cerebral hemorrhage undergoing minimally invasive surgery at the Department of Neurology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology between April 2005 and February 2007. PARTICIPANTS： Fifty-eight males and thirty-one females aged （52.7 ± 5.23） years （range, 28-73 years）. METHODS： Cranial CT was performed twice to objectively identify hematoma enlargement. Patients with hematoma enlargement prior to surgery were selected as the observation group （n = 30）, and those with no obvious hematoma changes served as the control group （n = 60）. Following cranial CT localization, the two groups underwent minimally invasive hematoma aspiration and drainage, according to Standardized Treatment Guidelines for Micro-invasive Aspiration and Drainage of Intracranial Hematoma. MAIN OUTCOME MEASURES： Hemorrhage site, coagulation function, diabetes history, and clinical symptoms. RESULTS： There were no significant differences in hemorrhage sites between the two groups （χ2 = 2.262, P 〉 0.05）. The percent of intemperance patients in the observation group was significantly larger than the control group （χ2 = 6.923, P 〈 0.01）. No significant differences in terms of percent of coagulation dysfunction or diabetes were determined between the two groups （χ2 = 0.03, 0.08, P 〉 0.05）. The percent of patients with clinical deterioration was significantly higher in the observation group, compared to the control group （χ2 = 25.57, P 〈 0.01）. CONCLUSION： Intemperance and preoperative clinical deterioration may increase incidence of hematoma enlargement prior to minimally invasive surgery in patients with hypertensive cerebral hemorrhage.
文摘AIM:To compare the difference between tumorinduced lymph node enlargement and inflammation-induced lymph node enlargement by contrast-enhanced ultrasonography and pathological findings. METHODS:A model of tumor-induced lymph node metastasis was prepared by embedding a VX2 tumor into the hind paws of white rabbits.A model of inflammation-induced enlargement was prepared by injecting a suspension of Escherichia coli into separate hind paws of white rabbits.Then,a solution of SonazoidTM(GE Healthcare,Oslo,Norway)was injected subcutaneously in the proximity of the lesion followed by contrast-enhanced ultrasonography of the enlarged popliteal lymph nodes. RESULTS:In the contrast-enhanced ultrasonography of the tumor-induced metastasis model,the sentinel lymph node was imaged.An area of filling defect was observed in that enlarged lymph node.In the histology examination,the area of filling defect corresponded to the metastatic lesion of the tumor.Contrast-enhanced ultrasonography of the model on inflammation-induced lymph node enlargement,and that of the acute inflam-mation model performed 3-7 d later,revealed dense staining that was comparatively uniform.The pathological findings showed acute lymphadenitis mainly due to infiltration of inflammatory cells.Contrast-enhanced ultrasonography that was performed 28 d post-infection in the acute inflammation model showed speckled staining.Inflammation-induced cell infiltration and fiberization,which are findings of chronic lymphadenitis, were seen in the pathological findings. CONCLUSION:Sentinel lymph node imaging was made possible by subcutaneous injection of SonazoidTM.Contrast-enhanced ultrasonography was suggested to be useful in differentiating tumor-induced enlargement and inflammation-induced enlargement of lymph nodes.
文摘Enlarged vestibular aqueduct(EVA), the most frequent identifiable cause of congenital hearing loss, is evaluated with high-definition multidetector CT in the axial plane. Our purpose was to determine which reformatted CT measurements are most reproducible. Seven multiplanar reformatted images were created for each of the 64 temporal bones in patients with EVA. Intraclass correlation coefficients(ICC) were used to assess inter-observer variability, and both linear regression and ROC analyses were used to compare the measurements with severity of hearing loss, as assessed by pure tone audiometry. All seven measurements had excellent inter-observer variability, with average-measure ICC ranging from 0.92 to 0.98. There was no statistically significant correlation between the radiologic degree of aqueduct enlargement and severity of hearing loss using any of the seven measurements; ROC analyses revealed areas under the curves ranging from 0.57 to 0.73. Optimal accuracy was obtained with a threshold of 1.75 mm as measured at the aqueductal aperture in the P€oschl plane, with sensitivity of 0.75 and specificity of0.63. Although the radiologic measurement may not serve as a reliable tool for assessing severity of EVA, P€oschl plane reformatting has proven to be better than conventional axial acquisition plane for identifying patients with clinically significant hearing loss.
