The inhibitory mechanism of copper（Ⅱ） on the aggegation of amyloid β-peptide （Aβ） was investigated by molecular dynamics simulations. The binding mode ofcopper（Ⅱ） with Aβ is characterized by the imidazole n...The inhibitory mechanism of copper（Ⅱ） on the aggegation of amyloid β-peptide （Aβ） was investigated by molecular dynamics simulations. The binding mode ofcopper（Ⅱ） with Aβ is characterized by the imidazole nitrogen atom, Nπ, of the histidine residue H 13, acting as the anchoring site, and the backbone＇s deprotoned amide nitogen atoms as the main binding sites. Drove by the coordination bonds and their induced hydrogen bond net, the conformations of Aβ converted from β-sheet non-β-sheet conformations, which destabilized the aggregation of Aβ into fibrils.展开更多
Objective: To investigate the value of urinary trypsi-nogen activation peptide (TAP) in the early predic-tion of severe acute pancreatitis and to compare itwith acute physiology and chronic health evaluationⅡ (APACHE...Objective: To investigate the value of urinary trypsi-nogen activation peptide (TAP) in the early predic-tion of severe acute pancreatitis and to compare itwith acute physiology and chronic health evaluationⅡ (APACHE Ⅱ).Methods: We assessed the predictive value of urinaryTAP concentrations measured by a competitive en-zyme-linked immunosorbent assay. Urine sampleswere collected for detecting TAP concentrations atadmission, and 24, 48, and 72 h from 41 patientswith acute pancreatitis (12 with severe disease, 29with mild disease) who presented within 48 h the on-set of symptoms and from 11 control patients, whileAPACHE Ⅱ scores were recorded at 48 h after ad-mission.Results: The peak median urinary TAP concentrationwas seen at admission. The median urinary TAPconcentration at admission for severe pancreatitis (95nmol/L) was significantly higher than the medianfor patients with mild pancreatitis (20 nmol/L, P【0. 005) and controls (15 nmol/L, P【0. 005). TAPconcentrations were significantly higher in patientswith severe acute pancreatitis than the median in pa-tients with mild pancreatitis (P【0. 05) and controls(P【0. 05) on days 2 to 3. The median APACHE Ⅱscores of severe patients were significantly differentfrom those of mild patients (10.5 vs 6.0, P【0.01).The sensitivity, specificity, positive predictive, andnegative predictive values of an admission urinaryTAP≥35 nmol/L for severe pancreatitis were91.7%, 89.7%, 78.6% and 96.3%, whereas 48 hafter admission the values for APACHE Ⅱ scores(≥9) were 75.0%, 72.7%, 52.9% and 87.5%. Inprediction of disease severity, the urine TAP concen-tration was much better than APACHE Ⅱ at 48 h.Conclusions: Urinary TAP obtained at the first 48 hof the onset of symptoms can predict severe acutepancreatitis. In prediction of disease severity, theurinary TAP is much better than APACHE Ⅱ score.展开更多
AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission.METHODS: Major databases including Medline, Embase, Science Cit...AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission.METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated.RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively.CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis.展开更多
目的:探讨三七总皂苷对慢性心力衰竭大鼠心脏功能、血浆利钠肽及血管紧张素Ⅱ的影响。方法:将60只健康雄性清洁级Wistar大鼠随机分为4组,即对照组、模型组、三七总皂苷低剂量组和三七总皂苷高剂量组,每组15只。除对照组外,其余3组均建...目的:探讨三七总皂苷对慢性心力衰竭大鼠心脏功能、血浆利钠肽及血管紧张素Ⅱ的影响。方法:将60只健康雄性清洁级Wistar大鼠随机分为4组,即对照组、模型组、三七总皂苷低剂量组和三七总皂苷高剂量组,每组15只。除对照组外,其余3组均建立慢性心力衰竭大鼠模型。对三七总皂苷低剂量组和三七总皂苷高剂量组大鼠分别给予51、105 mg·kg -1 剂量的三七总皂苷治疗。检测各组大鼠平均动脉压(mean arterial pressure,MAP)、左心室收缩压(left ventricular systolic pressure,LVSP)、左心室压最大上升速率(maximal rate of the increase of left ventricular pressure,+dp/dt)、左心室压最大下降速率(maximal rate of the decrease of left ventricular pressure,- dp/dt),以及大鼠血清和心肌组织中利钠肽、血管紧张素Ⅱ水平。结果:与对照组比较,模型组、三七总皂苷低剂量组、三七总皂苷高剂量组大鼠MAP、LVSP水平,+dp/dt、- dp/dt数值均明显降低,利钠肽、血管紧张素Ⅱ水平均明显升高,差异均有统计学意义(均 P <0.05)。与模型组比较,三七总皂苷低剂量组、三七总皂苷高剂量组大鼠MAP、LVSP水平,+dp/dt、- dp/dt数值均明显升高,利钠肽及血管紧张素Ⅱ水平均明显降低,且高剂量组变化趋势更明显,差异均有统计学意义(均 P <0.05)。模型组心肌细胞排列紊乱,心肌纤维呈波浪形,部分断裂;三七总皂苷低、高剂量组大鼠心肌细胞排列较整齐,边缘清楚,无肌纤维断裂,胞浆纹理清晰。结论:三七总皂苷可通过调节慢性心力衰竭大鼠心脏功能指标,改善心室收缩肌舒张功能,并降低利钠肽及血管紧张素Ⅱ水平,有效防止心肌重构,对慢性心力衰竭具有一定的治疗效果。展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.30470408 and 20637010).
文摘The inhibitory mechanism of copper（Ⅱ） on the aggegation of amyloid β-peptide （Aβ） was investigated by molecular dynamics simulations. The binding mode ofcopper（Ⅱ） with Aβ is characterized by the imidazole nitrogen atom, Nπ, of the histidine residue H 13, acting as the anchoring site, and the backbone＇s deprotoned amide nitogen atoms as the main binding sites. Drove by the coordination bonds and their induced hydrogen bond net, the conformations of Aβ converted from β-sheet non-β-sheet conformations, which destabilized the aggregation of Aβ into fibrils.
文摘Objective: To investigate the value of urinary trypsi-nogen activation peptide (TAP) in the early predic-tion of severe acute pancreatitis and to compare itwith acute physiology and chronic health evaluationⅡ (APACHE Ⅱ).Methods: We assessed the predictive value of urinaryTAP concentrations measured by a competitive en-zyme-linked immunosorbent assay. Urine sampleswere collected for detecting TAP concentrations atadmission, and 24, 48, and 72 h from 41 patientswith acute pancreatitis (12 with severe disease, 29with mild disease) who presented within 48 h the on-set of symptoms and from 11 control patients, whileAPACHE Ⅱ scores were recorded at 48 h after ad-mission.Results: The peak median urinary TAP concentrationwas seen at admission. The median urinary TAPconcentration at admission for severe pancreatitis (95nmol/L) was significantly higher than the medianfor patients with mild pancreatitis (20 nmol/L, P【0. 005) and controls (15 nmol/L, P【0. 005). TAPconcentrations were significantly higher in patientswith severe acute pancreatitis than the median in pa-tients with mild pancreatitis (P【0. 05) and controls(P【0. 05) on days 2 to 3. The median APACHE Ⅱscores of severe patients were significantly differentfrom those of mild patients (10.5 vs 6.0, P【0.01).The sensitivity, specificity, positive predictive, andnegative predictive values of an admission urinaryTAP≥35 nmol/L for severe pancreatitis were91.7%, 89.7%, 78.6% and 96.3%, whereas 48 hafter admission the values for APACHE Ⅱ scores(≥9) were 75.0%, 72.7%, 52.9% and 87.5%. Inprediction of disease severity, the urine TAP concen-tration was much better than APACHE Ⅱ at 48 h.Conclusions: Urinary TAP obtained at the first 48 hof the onset of symptoms can predict severe acutepancreatitis. In prediction of disease severity, theurinary TAP is much better than APACHE Ⅱ score.
基金Supported by Technology Supported Program of Sichuan Province, No. 2011SZ0291the National Natural Science Foundation of China, No. 81072910National Institute for Health Research, United Kingdom
文摘AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission.METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated.RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively.CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis.
文摘目的:探讨三七总皂苷对慢性心力衰竭大鼠心脏功能、血浆利钠肽及血管紧张素Ⅱ的影响。方法:将60只健康雄性清洁级Wistar大鼠随机分为4组,即对照组、模型组、三七总皂苷低剂量组和三七总皂苷高剂量组,每组15只。除对照组外,其余3组均建立慢性心力衰竭大鼠模型。对三七总皂苷低剂量组和三七总皂苷高剂量组大鼠分别给予51、105 mg·kg -1 剂量的三七总皂苷治疗。检测各组大鼠平均动脉压(mean arterial pressure,MAP)、左心室收缩压(left ventricular systolic pressure,LVSP)、左心室压最大上升速率(maximal rate of the increase of left ventricular pressure,+dp/dt)、左心室压最大下降速率(maximal rate of the decrease of left ventricular pressure,- dp/dt),以及大鼠血清和心肌组织中利钠肽、血管紧张素Ⅱ水平。结果:与对照组比较,模型组、三七总皂苷低剂量组、三七总皂苷高剂量组大鼠MAP、LVSP水平,+dp/dt、- dp/dt数值均明显降低,利钠肽、血管紧张素Ⅱ水平均明显升高,差异均有统计学意义(均 P <0.05)。与模型组比较,三七总皂苷低剂量组、三七总皂苷高剂量组大鼠MAP、LVSP水平,+dp/dt、- dp/dt数值均明显升高,利钠肽及血管紧张素Ⅱ水平均明显降低,且高剂量组变化趋势更明显,差异均有统计学意义(均 P <0.05)。模型组心肌细胞排列紊乱,心肌纤维呈波浪形,部分断裂;三七总皂苷低、高剂量组大鼠心肌细胞排列较整齐,边缘清楚,无肌纤维断裂,胞浆纹理清晰。结论:三七总皂苷可通过调节慢性心力衰竭大鼠心脏功能指标,改善心室收缩肌舒张功能,并降低利钠肽及血管紧张素Ⅱ水平,有效防止心肌重构,对慢性心力衰竭具有一定的治疗效果。
