Niemann-Pick disease type C(NPC) is a fatal, neurovisceral lipid storage disease, neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons, progressive neuronal loss, neurofibrillary ta...Niemann-Pick disease type C(NPC) is a fatal, neurovisceral lipid storage disease, neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons, progressive neuronal loss, neurofibrillary tangles(NFTs) formation, and axonal spheroids(AS). Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC(npc mice). With a goal of elucidating the mechanisms underlying the lesion formation, we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2, cdk4, and cdk5 in lesion formation in young npc mice. Cytoskeletal lesions were detectable in npc mice at three weeks of age. Importantly, concomitant activation of cdc2/cyclin B1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected. The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice, and this activation contributed to the lesion formation. We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2, cdk4, and cdk5 activation. Furthermore, cdc2/cyclin B1 may act as a key initial player one week earlier. Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.展开更多
In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 (cdk-5) inhibition in mice with Niemann-Pick disease type C (NPC) (npc-/-), recombinant adeno-associated virus (rAAV) carrying the small...In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 (cdk-5) inhibition in mice with Niemann-Pick disease type C (NPC) (npc-/-), recombinant adeno-associated virus (rAAV) carrying the small interfering RNA (siRNA) specific for cdk-5 gene was injected into 3-day-old npc-/-mice intracerebroventricularly. The rAAV-GFP-injected age-matched npc-/-mice and non-surgery age-matched npc-/-mice were employed as controls (n=6―10/group). From the 4th to 8th week after the treatment, mice were weighed, and evaluated for limb motor activity by using the coat hanger test once a week. Eight-week-old npc-/-mice were sacrificed by decapitation, and brains were quickly dissected and halved sagittally. Immunohistochemistry, Western blotting, and HE staining were used to evaluate the neuropathology in npc-/-mice. The results showed that rAAV-cdk-5-siRNA-GFP significantly reduced the number of axonal spheroids, delayed the death of Purkinje neurons, ameliorated motor defects in npc-/-mice, and significantly attenuated the hyper-phosphorylation of tau proteins. These data suggested that inhibition of cdk-5 activity has neuropro-tective effect on neurons in NPC mice.展开更多
AIM:To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma(HCC).METHODS:We studied 232 patients,who underwent liver biopsy for type C c...AIM:To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma(HCC).METHODS:We studied 232 patients,who underwent liver biopsy for type C chronic liver disease between 1992 and 2009,with sustained virological response(SVR)after interferon therapy.The patients were divided into two groups according to the F stage 0+1+2 group(n = 182)and F3+4 group(n = 50).We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0+1+2 and F3+4 groups.Then,the background factors and liver histopathological findings,including the degree of fibrosis,F stage,inflammation,necrosis,bile duct obstruction,fat deposition,and degree of irregular regeneration(IR)of hepatocytes,were correlated with the risk of developing HCC.RESULTS:HCC developed in three of 182(1.6%)patients in the F0+1+2 group,and four of 50(8.0%)in the F3+4 group.The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3+4 group(log rank test P = 0.0224).The presence of atypical hepatocytes among IR of hepatocytes in the F3+4 group resulted in a higher cumulative incidence of HCC,and was significantly correlated with risk of HCC development(RR = 20.748,95%CI:1.335-322.5,P = 0.0303).CONCLUSION:Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.展开更多
目的报道1例在鞍区精原细胞瘤放化疗后出现C型尼曼-匹克病(Niemann-Pick disease type C,NPC)的病例,加强对尼曼-匹克病(Niemann-Pick disease,NPD)的了解。方法对南部战区总医院内分泌科2021年6月收治的1例鞍区精原细胞瘤切除术、放化...目的报道1例在鞍区精原细胞瘤放化疗后出现C型尼曼-匹克病(Niemann-Pick disease type C,NPC)的病例,加强对尼曼-匹克病(Niemann-Pick disease,NPD)的了解。方法对南部战区总医院内分泌科2021年6月收治的1例鞍区精原细胞瘤切除术、放化疗后逐渐出现垂体功能减退、重度肝损害、肝脾大,激素替代治疗后引起继发性糖尿病的青少年患者长达4年的病史进行回顾性分析。结果本例患者为青少年女性,鞍区精原细胞瘤切除术及放化疗后,逐渐出现不同程度血细胞下降、脂代谢异常、肝功能异常、肝脾增大等,行骨髓穿刺,形态学发现2%尼曼-匹克细胞,最终诊断为NPC。经输血、护肝、胰岛素降糖、激素替代等对症治疗后,各项指标较治疗前好转,精神较入院时稍好转,但患者仍存在黄疸、肝脾大,偶有精神异常。目前继续门诊随访,予对症治疗。结论对于颅内肿瘤术后或放化疗后所致内分泌与代谢相关症状,且同时伴有难以解释的神经、精神、脏器功能异常时,要考虑到NPC的可能性,可通过骨髓穿刺涂片发现尼曼-匹克细胞初步诊断。目前NPC的治疗以对症为主。展开更多
Objective: To study the relationship between Cystatin C (Cys-C) level and the development of coronary heart disease in elderly patients with type 2 diabetes mellitus (T2DM). Methods: 120 cases of elderly diabetic pati...Objective: To study the relationship between Cystatin C (Cys-C) level and the development of coronary heart disease in elderly patients with type 2 diabetes mellitus (T2DM). Methods: 120 cases of elderly diabetic patients were involved in this study from October 2013 to November 2015 in Depart-ment of Endocrinology and Cardiology. All patients underwent the detection of routine flash dual-source coronary computed tomography angioplasty (CCTA), Cys-C, hemoglobin A1c (HbA1c). According to the difference of CCTA results, the patients were divided into DM1 group (with normal coronary CTA), DM2 group (with a coronary artery stenosis rate < 50%), DM3 group (with a coronary artery stenosis rate of 50%-74%) and DM4 group (with a coronary artery stenosis rate of ≥ 75%). The levels of Cys-C and HbA1c were compared in the four groups. Results: The blood levels of Cys-C and HbA1c showed significant differences between DM1, DM2, DM3 and DM4 group (p <.05). The age, heart rate, blood pressure showed no statistical differences between the groups. The level of Cys-C was positively correlated with HbA1c. Conclusions: The blood level of Cys-C in the elderly patients with T2DM increased with the increase of the degree of coronary artery stenosis. Blood Cys-C may be used as an early predictor of coronary artery lesions in elderly patients with T2DM.展开更多
The present paper evaluated Friedman’s and Rosenman’s Type A and Type B personality theory.According to the authors,Type A personality has been linked to coronary heart disease and other heart problems.After discuss...The present paper evaluated Friedman’s and Rosenman’s Type A and Type B personality theory.According to the authors,Type A personality has been linked to coronary heart disease and other heart problems.After discussing the basic concepts of the theory,it was important to analyze different research papers that utilized the theory in different domains.Then the discussion moved forward to new personality types that have been discovered throughout the years(Types C,D,T).Then a summary of the criticism that the theory has received is included.Finally,future research ideas and limitations of the theory were included.展开更多
Objective: The purpose of this study was to provide an initial assessment of the effectiveness of the high nutrient density (HND) diet on glycemic control and cardiovascular risk factors in participants with type 2 di...Objective: The purpose of this study was to provide an initial assessment of the effectiveness of the high nutrient density (HND) diet on glycemic control and cardiovascular risk factors in participants with type 2 diabetes. Design: This was a retrospective case series study. Participants were 13 adult type 2 diabetic U.S. women and men between the ages of 30 - 80 years old. Glycosylated hemoglobin (HbA1C), lipid profile, blood pressure, BMI, and medication requirements before and after commencement of the HND diet were compared. Results: After a median length on the HND diet of 7 months, the mean HbA1C dropped from 8.2% to 5.8% (p = 0.002), with sixty-two percent of participants reaching normoglycemic levels (HbA1C p = 0.0004 for systolic blood pressure, p = 0.01 for diastolic blood pressure). Triglycerides significantly decreased from a mean of 171 mg/dl to a mean of 103 mg/dl (p = 0.02). The HDL increased significantly from 48.3 mg/dl to 54.6 mg/dl (p = 0.03). The mean number of medications dropped from 4 to 1 (p = 0.0006). Conclusions: The HND diet was very effective in controlling glycemic levels and cardiovascular risk factors in 13 participants with type 2 diabetes. Therefore, there is a well-justified need for further study with the HND diet.展开更多
The aim was to assess whether temporal changes in the initial management for children diagnosed with type 1 diabetes over a ten year period affected metabolic control two years after diagnosis. A further aim was to in...The aim was to assess whether temporal changes in the initial management for children diagnosed with type 1 diabetes over a ten year period affected metabolic control two years after diagnosis. A further aim was to investigate if social factors, registered at diagnosis, had an impact on metabolic control two years after diagnosis. During the years 1997-2006, 247 children and adolescents were diagnosed with type 1 diabetes at a University Hospital in Sweden. The analysed data included HbA1c, pH at diagnosis, initial intravenous insulin infusion and length of hospital stay at diag?nosis, subcutaneous insulin type, number of diabetes check-up visits, emergency visits, re-admissions and social factors. Length of hospital stay decreased significantly over the ten year period. Neither hospital stay nor differences in insulin treatment was significantly correlated with children’s metabolic control over time. Length of hospital stay was not re?lated with families’ social stress situation. However, girls in families with more family stress at the time of diagnosis had higher HbA1c during follow-up than girls with less family stress or boys. Factors of importance for the child’s long-term metabolic control need to be further investigated so the initial management can be tailored to each individual family’s needs. This would imply an effective utilization of both families’ and health care resources.展开更多
基金supported by the National Natural Science Foundation of China(No.81271406)
文摘Niemann-Pick disease type C(NPC) is a fatal, neurovisceral lipid storage disease, neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons, progressive neuronal loss, neurofibrillary tangles(NFTs) formation, and axonal spheroids(AS). Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC(npc mice). With a goal of elucidating the mechanisms underlying the lesion formation, we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2, cdk4, and cdk5 in lesion formation in young npc mice. Cytoskeletal lesions were detectable in npc mice at three weeks of age. Importantly, concomitant activation of cdc2/cyclin B1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected. The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice, and this activation contributed to the lesion formation. We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2, cdk4, and cdk5 activation. Furthermore, cdc2/cyclin B1 may act as a key initial player one week earlier. Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30400141, 30670737)
文摘In order to investigate the neuroprotective effects of cyclin-dependent kinase-5 (cdk-5) inhibition in mice with Niemann-Pick disease type C (NPC) (npc-/-), recombinant adeno-associated virus (rAAV) carrying the small interfering RNA (siRNA) specific for cdk-5 gene was injected into 3-day-old npc-/-mice intracerebroventricularly. The rAAV-GFP-injected age-matched npc-/-mice and non-surgery age-matched npc-/-mice were employed as controls (n=6―10/group). From the 4th to 8th week after the treatment, mice were weighed, and evaluated for limb motor activity by using the coat hanger test once a week. Eight-week-old npc-/-mice were sacrificed by decapitation, and brains were quickly dissected and halved sagittally. Immunohistochemistry, Western blotting, and HE staining were used to evaluate the neuropathology in npc-/-mice. The results showed that rAAV-cdk-5-siRNA-GFP significantly reduced the number of axonal spheroids, delayed the death of Purkinje neurons, ameliorated motor defects in npc-/-mice, and significantly attenuated the hyper-phosphorylation of tau proteins. These data suggested that inhibition of cdk-5 activity has neuropro-tective effect on neurons in NPC mice.
文摘AIM:To evaluate the histopathological findings of type C liver disease to determine risk factors for development of hepatocellular carcinoma(HCC).METHODS:We studied 232 patients,who underwent liver biopsy for type C chronic liver disease between 1992 and 2009,with sustained virological response(SVR)after interferon therapy.The patients were divided into two groups according to the F stage 0+1+2 group(n = 182)and F3+4 group(n = 50).We prospectively observed and compared the incidence of HCC of the patients with SVR in the F0+1+2 and F3+4 groups.Then,the background factors and liver histopathological findings,including the degree of fibrosis,F stage,inflammation,necrosis,bile duct obstruction,fat deposition,and degree of irregular regeneration(IR)of hepatocytes,were correlated with the risk of developing HCC.RESULTS:HCC developed in three of 182(1.6%)patients in the F0+1+2 group,and four of 50(8.0%)in the F3+4 group.The cumulative incidence of HCC in the former group was found to be significantly lower than in the F3+4 group(log rank test P = 0.0224).The presence of atypical hepatocytes among IR of hepatocytes in the F3+4 group resulted in a higher cumulative incidence of HCC,and was significantly correlated with risk of HCC development(RR = 20.748,95%CI:1.335-322.5,P = 0.0303).CONCLUSION:Atypical hepatocytes among the histopathological findings of type C liver disease may be an important risk factor for HCC development along with progression of liver fibrosis.
文摘目的报道1例在鞍区精原细胞瘤放化疗后出现C型尼曼-匹克病(Niemann-Pick disease type C,NPC)的病例,加强对尼曼-匹克病(Niemann-Pick disease,NPD)的了解。方法对南部战区总医院内分泌科2021年6月收治的1例鞍区精原细胞瘤切除术、放化疗后逐渐出现垂体功能减退、重度肝损害、肝脾大,激素替代治疗后引起继发性糖尿病的青少年患者长达4年的病史进行回顾性分析。结果本例患者为青少年女性,鞍区精原细胞瘤切除术及放化疗后,逐渐出现不同程度血细胞下降、脂代谢异常、肝功能异常、肝脾增大等,行骨髓穿刺,形态学发现2%尼曼-匹克细胞,最终诊断为NPC。经输血、护肝、胰岛素降糖、激素替代等对症治疗后,各项指标较治疗前好转,精神较入院时稍好转,但患者仍存在黄疸、肝脾大,偶有精神异常。目前继续门诊随访,予对症治疗。结论对于颅内肿瘤术后或放化疗后所致内分泌与代谢相关症状,且同时伴有难以解释的神经、精神、脏器功能异常时,要考虑到NPC的可能性,可通过骨髓穿刺涂片发现尼曼-匹克细胞初步诊断。目前NPC的治疗以对症为主。
文摘Objective: To study the relationship between Cystatin C (Cys-C) level and the development of coronary heart disease in elderly patients with type 2 diabetes mellitus (T2DM). Methods: 120 cases of elderly diabetic patients were involved in this study from October 2013 to November 2015 in Depart-ment of Endocrinology and Cardiology. All patients underwent the detection of routine flash dual-source coronary computed tomography angioplasty (CCTA), Cys-C, hemoglobin A1c (HbA1c). According to the difference of CCTA results, the patients were divided into DM1 group (with normal coronary CTA), DM2 group (with a coronary artery stenosis rate < 50%), DM3 group (with a coronary artery stenosis rate of 50%-74%) and DM4 group (with a coronary artery stenosis rate of ≥ 75%). The levels of Cys-C and HbA1c were compared in the four groups. Results: The blood levels of Cys-C and HbA1c showed significant differences between DM1, DM2, DM3 and DM4 group (p <.05). The age, heart rate, blood pressure showed no statistical differences between the groups. The level of Cys-C was positively correlated with HbA1c. Conclusions: The blood level of Cys-C in the elderly patients with T2DM increased with the increase of the degree of coronary artery stenosis. Blood Cys-C may be used as an early predictor of coronary artery lesions in elderly patients with T2DM.
文摘The present paper evaluated Friedman’s and Rosenman’s Type A and Type B personality theory.According to the authors,Type A personality has been linked to coronary heart disease and other heart problems.After discussing the basic concepts of the theory,it was important to analyze different research papers that utilized the theory in different domains.Then the discussion moved forward to new personality types that have been discovered throughout the years(Types C,D,T).Then a summary of the criticism that the theory has received is included.Finally,future research ideas and limitations of the theory were included.
文摘Objective: The purpose of this study was to provide an initial assessment of the effectiveness of the high nutrient density (HND) diet on glycemic control and cardiovascular risk factors in participants with type 2 diabetes. Design: This was a retrospective case series study. Participants were 13 adult type 2 diabetic U.S. women and men between the ages of 30 - 80 years old. Glycosylated hemoglobin (HbA1C), lipid profile, blood pressure, BMI, and medication requirements before and after commencement of the HND diet were compared. Results: After a median length on the HND diet of 7 months, the mean HbA1C dropped from 8.2% to 5.8% (p = 0.002), with sixty-two percent of participants reaching normoglycemic levels (HbA1C p = 0.0004 for systolic blood pressure, p = 0.01 for diastolic blood pressure). Triglycerides significantly decreased from a mean of 171 mg/dl to a mean of 103 mg/dl (p = 0.02). The HDL increased significantly from 48.3 mg/dl to 54.6 mg/dl (p = 0.03). The mean number of medications dropped from 4 to 1 (p = 0.0006). Conclusions: The HND diet was very effective in controlling glycemic levels and cardiovascular risk factors in 13 participants with type 2 diabetes. Therefore, there is a well-justified need for further study with the HND diet.
文摘The aim was to assess whether temporal changes in the initial management for children diagnosed with type 1 diabetes over a ten year period affected metabolic control two years after diagnosis. A further aim was to investigate if social factors, registered at diagnosis, had an impact on metabolic control two years after diagnosis. During the years 1997-2006, 247 children and adolescents were diagnosed with type 1 diabetes at a University Hospital in Sweden. The analysed data included HbA1c, pH at diagnosis, initial intravenous insulin infusion and length of hospital stay at diag?nosis, subcutaneous insulin type, number of diabetes check-up visits, emergency visits, re-admissions and social factors. Length of hospital stay decreased significantly over the ten year period. Neither hospital stay nor differences in insulin treatment was significantly correlated with children’s metabolic control over time. Length of hospital stay was not re?lated with families’ social stress situation. However, girls in families with more family stress at the time of diagnosis had higher HbA1c during follow-up than girls with less family stress or boys. Factors of importance for the child’s long-term metabolic control need to be further investigated so the initial management can be tailored to each individual family’s needs. This would imply an effective utilization of both families’ and health care resources.
