AIM：To identify the pathological role of amyloid beta（Aβ） deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells（RPE） layer and the associated structural and functi...AIM：To identify the pathological role of amyloid beta（Aβ） deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells（RPE） layer and the associated structural and functional changes in Alzheimer＇s disease transgenic mice.METHODS：RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic（NTG） mice over 20 months old were examined.Histological changes were investigated via hematoxylin and eosin（H＆E） staining and transmission electron microscopy（TEM） examination,whereas the expression of amyloid precursor protein（APP）,Aβ,Zonula occludens-1（ZO-1） and Ionized calcium binding adaptor molecule-1（IBA-1） were investigated using immunohistochemistry and immunofluorescence techniques.All of the obtained results were quantitatively and statistically analyzed.RESULTS：In aged transgenic mice,an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice.The RPE demonstrated some vacuole changes,shortened basal infoldings and basal deposition in histopathological examination and TEM tests,wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence.Furthermore,IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch＇s membrane（Br M） complex,which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice.The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts.CONCLUSION：The observed Aβ deposition in the RPE layer may cause RPE dysfunction,which is associated with microglia cells infiltration into the retina of aged transgenic mice,suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.展开更多
OBJECTIVE To evaluate the association of longitudinal changes in physical activity(PA)with long-term outcomes after im-plantable cardioverter-defibrillator(ICD)or cardiac resynchronization therapy defibrillator(CRT-D)...OBJECTIVE To evaluate the association of longitudinal changes in physical activity(PA)with long-term outcomes after im-plantable cardioverter-defibrillator(ICD)or cardiac resynchronization therapy defibrillator(CRT-D)implantation.METHODS Patients with ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed.Accelerometer-de-rived PA changes over 12 months post implantation were obtained from the archived home monitoring data.The primary end-points were cardiac death and all-cause mortality.The secondary endpoints were the first ventricular arrthymia(VA)and first ap-propriate ICD shock.RESULTS In 705 patients,446(63.3%)patients showed improved PA over 12 months after implantation.During a mean 61.5-month follow-up duration,99 cardiac deaths(14.0%)and 153 all-cause deaths(21.7%)occurred.Compared to reduced/un-changed PA,improved PA over 12 months could result in significantly reduced risks of cardiac death(improved PA≤30 min:hazard ratio(HR)=0.494,95%CI:0.288−0.848;>30 min:HR=0.390,95%CI:0.235−0.648)and all-cause mortality(improved PA≤30 min:HR=0.467,95%CI:0.299−0.728;>30 min:HR=0.451,95%CI:0.304−0.669).No differences in the VAs or ICD shocks were observed across different groups of PA changes.PA changes can predict the risks of cardiac death only in the low baseline PA group,but improved PA was associated with 56.7%,57.4%,and 62.3%reduced risks of all-cause mortality in the low,moderate,and high baseline PA groups,respectively,than reduced/unchanged PA.CONCLUSIONS Improved PA could protect aganist cardiac death and all-cause mortality,probably reflecting better clinical efficacy after ICD/CRT-D implantation.Low-intensity exercise training might be encouraged among patients with different baseline PA levels.展开更多
基金Supported by the National Natural Science Foundation of China(No.81430009No.81400424)the Science and Technology Research and Development Project of Shaanxi Province(No.2014K11-03-07-04)
文摘AIM：To identify the pathological role of amyloid beta（Aβ） deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells（RPE） layer and the associated structural and functional changes in Alzheimer＇s disease transgenic mice.METHODS：RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic（NTG） mice over 20 months old were examined.Histological changes were investigated via hematoxylin and eosin（H＆E） staining and transmission electron microscopy（TEM） examination,whereas the expression of amyloid precursor protein（APP）,Aβ,Zonula occludens-1（ZO-1） and Ionized calcium binding adaptor molecule-1（IBA-1） were investigated using immunohistochemistry and immunofluorescence techniques.All of the obtained results were quantitatively and statistically analyzed.RESULTS：In aged transgenic mice,an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice.The RPE demonstrated some vacuole changes,shortened basal infoldings and basal deposition in histopathological examination and TEM tests,wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence.Furthermore,IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch＇s membrane（Br M） complex,which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice.The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts.CONCLUSION：The observed Aβ deposition in the RPE layer may cause RPE dysfunction,which is associated with microglia cells infiltration into the retina of aged transgenic mice,suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.
基金supported by Natural Science Foundation of China (81470466)the National Science&Technology Pillar Program during the12th Five-Year Plan Period (2011BAI11B02)
文摘OBJECTIVE To evaluate the association of longitudinal changes in physical activity(PA)with long-term outcomes after im-plantable cardioverter-defibrillator(ICD)or cardiac resynchronization therapy defibrillator(CRT-D)implantation.METHODS Patients with ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed.Accelerometer-de-rived PA changes over 12 months post implantation were obtained from the archived home monitoring data.The primary end-points were cardiac death and all-cause mortality.The secondary endpoints were the first ventricular arrthymia(VA)and first ap-propriate ICD shock.RESULTS In 705 patients,446(63.3%)patients showed improved PA over 12 months after implantation.During a mean 61.5-month follow-up duration,99 cardiac deaths(14.0%)and 153 all-cause deaths(21.7%)occurred.Compared to reduced/un-changed PA,improved PA over 12 months could result in significantly reduced risks of cardiac death(improved PA≤30 min:hazard ratio(HR)=0.494,95%CI:0.288−0.848;>30 min:HR=0.390,95%CI:0.235−0.648)and all-cause mortality(improved PA≤30 min:HR=0.467,95%CI:0.299−0.728;>30 min:HR=0.451,95%CI:0.304−0.669).No differences in the VAs or ICD shocks were observed across different groups of PA changes.PA changes can predict the risks of cardiac death only in the low baseline PA group,but improved PA was associated with 56.7%,57.4%,and 62.3%reduced risks of all-cause mortality in the low,moderate,and high baseline PA groups,respectively,than reduced/unchanged PA.CONCLUSIONS Improved PA could protect aganist cardiac death and all-cause mortality,probably reflecting better clinical efficacy after ICD/CRT-D implantation.Low-intensity exercise training might be encouraged among patients with different baseline PA levels.
