BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL system...BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.展开更多
Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the ...Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the relative strengths of liposome and polymersome drug delivery systems without their respective weaknesses.However,little is known about their properties and how they could be tailored.Currently,most methods of investigation are limited to the microscale.Here we provide a brief review on hybrid vesicle systems with a specific focus on recent developments demonstrating that nanoscale hybrid vesicles have different properties from their macroscale counterparts.展开更多
Many studies had been focused on designing tacrolimus sustained release preparations based on solid dispersion technique, but no one had tried to employ mesoporous silica as the carrier material to realize this goal. ...Many studies had been focused on designing tacrolimus sustained release preparations based on solid dispersion technique, but no one had tried to employ mesoporous silica as the carrier material to realize this goal. The purpose of this study was to develop a novel, simple and environmental friendly drug loading method with mesoporous silica to obtain tacrolimus sustained-release preparation. Tacrolimus was firstly dissolved in the molten mixed lipid composed of Compritol 888 ATO and Gelucire 50/13 to prepare a drug loaded lipid-based drug delivery systems(LBDDS), then the liquid LBDDS was adsorbed by mesoporous silica to transfer the liquid into solid powder, ie. the tacrolimus sustained release silica-lipid hybrid(SLH). The SLH was characterized by SEM, CLSM, XRPD and DSC, and the in vitro drug release was tested using a paddle method. SEM and CLSM observation showed that the LBDDS was efficiently distributed throughout the pores of the silica. The results of DSC and XRPD illustrated that the lipid existed inside the silica at amorphous state. The drug-loaded SLH showed good flowability, compressibility, compactibilty and two-phase in vitro drug release process within 24 hours, which did not change obviously even after storage at 40 °C for 10 d.The present study provided a novel and simple method to prepare tacrolimus sustained release powder, which provided a feasible solution to solidify the liquid LBDDS of not only extended drug release behavior, but also improved stability and micromeritic properties.展开更多
Enhanced stability of polyplexes in physiological condition was an important prerequisite for successful systemic gene delivery.Herein novel method was reported to develop stable gene vector by nanotechnology.Thiolate...Enhanced stability of polyplexes in physiological condition was an important prerequisite for successful systemic gene delivery.Herein novel method was reported to develop stable gene vector by nanotechnology.Thiolated polyplexes were constructed and then cross-linked with gold nanoparticles(AuNPs)by gold-thiol interactions.TEM pictures showed that AuNPs were attached to the shell of spherical polyplexes.The hybrid gene vector was stable enough in physiological condition and maintained efficient transfectio...展开更多
共享模式是电商逆向物流的新发展趋势,在共享车辆与客户订单的条件下,考虑带时间窗约束的客户同时取送货情景,建立了MJVRPSDPTW(multi-centers joint vehicle routing problem with simultaneous delivery and pick-up and time window...共享模式是电商逆向物流的新发展趋势,在共享车辆与客户订单的条件下,考虑带时间窗约束的客户同时取送货情景,建立了MJVRPSDPTW(multi-centers joint vehicle routing problem with simultaneous delivery and pick-up and time window)模型。接着设计一种基于大邻域搜索的混合遗传算法进行求解,针对“多对多网络”设置虚拟中心并利用整体法优化,同时融合大邻域搜索算法中的“破坏”与“修复”算子,增强算法寻优能力。通过多组算例对比实验,证明该算法优于两阶段规划法与经典遗传算法。基于优化后的网络,利用Shapley值法对不同联盟情况下的各物流企业进行利润分配,结果证明大联盟最稳定且共同利润最大。展开更多
文摘BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.
基金the work from the European Research Council under the European Union's Seventh Framework Program(FP/2007-2013)/ERC grant agreement No.310034the Austrian Science Fund(FWF)grant No.I 3064.
文摘Hybrid lipopolymer vesicles are membrane vesicles that can be self-assembled on both the micro-and nano-scale.On the nanoscale,they are potential novel smart materials for drug delivery systems that could combine the relative strengths of liposome and polymersome drug delivery systems without their respective weaknesses.However,little is known about their properties and how they could be tailored.Currently,most methods of investigation are limited to the microscale.Here we provide a brief review on hybrid vesicle systems with a specific focus on recent developments demonstrating that nanoscale hybrid vesicles have different properties from their macroscale counterparts.
文摘Many studies had been focused on designing tacrolimus sustained release preparations based on solid dispersion technique, but no one had tried to employ mesoporous silica as the carrier material to realize this goal. The purpose of this study was to develop a novel, simple and environmental friendly drug loading method with mesoporous silica to obtain tacrolimus sustained-release preparation. Tacrolimus was firstly dissolved in the molten mixed lipid composed of Compritol 888 ATO and Gelucire 50/13 to prepare a drug loaded lipid-based drug delivery systems(LBDDS), then the liquid LBDDS was adsorbed by mesoporous silica to transfer the liquid into solid powder, ie. the tacrolimus sustained release silica-lipid hybrid(SLH). The SLH was characterized by SEM, CLSM, XRPD and DSC, and the in vitro drug release was tested using a paddle method. SEM and CLSM observation showed that the LBDDS was efficiently distributed throughout the pores of the silica. The results of DSC and XRPD illustrated that the lipid existed inside the silica at amorphous state. The drug-loaded SLH showed good flowability, compressibility, compactibilty and two-phase in vitro drug release process within 24 hours, which did not change obviously even after storage at 40 °C for 10 d.The present study provided a novel and simple method to prepare tacrolimus sustained release powder, which provided a feasible solution to solidify the liquid LBDDS of not only extended drug release behavior, but also improved stability and micromeritic properties.
基金the National Natural Science Foundation of China(No.50403021)Natural Science Foundation of Zhejiang Province(No.Y407173)the Education Department of Zhejiang Province(No.20051498)
文摘Enhanced stability of polyplexes in physiological condition was an important prerequisite for successful systemic gene delivery.Herein novel method was reported to develop stable gene vector by nanotechnology.Thiolated polyplexes were constructed and then cross-linked with gold nanoparticles(AuNPs)by gold-thiol interactions.TEM pictures showed that AuNPs were attached to the shell of spherical polyplexes.The hybrid gene vector was stable enough in physiological condition and maintained efficient transfectio...
文摘共享模式是电商逆向物流的新发展趋势,在共享车辆与客户订单的条件下,考虑带时间窗约束的客户同时取送货情景,建立了MJVRPSDPTW(multi-centers joint vehicle routing problem with simultaneous delivery and pick-up and time window)模型。接着设计一种基于大邻域搜索的混合遗传算法进行求解,针对“多对多网络”设置虚拟中心并利用整体法优化,同时融合大邻域搜索算法中的“破坏”与“修复”算子,增强算法寻优能力。通过多组算例对比实验,证明该算法优于两阶段规划法与经典遗传算法。基于优化后的网络,利用Shapley值法对不同联盟情况下的各物流企业进行利润分配,结果证明大联盟最稳定且共同利润最大。
