Background:Liver diseases are a major contributor to both morbidity and mortality.Conditional knockout animals are always produced through crossing floxed animals with a tissue-specific Cre animal.The use of floxed ra...Background:Liver diseases are a major contributor to both morbidity and mortality.Conditional knockout animals are always produced through crossing floxed animals with a tissue-specific Cre animal.The use of floxed rat resource has rapidly increased,but the liver-specific Cre rat lines for studying liver diseases and interested genes are limited,especially in a spatially and temporally restricted manner.Methods:RNA sequencing and real-time polymerase chain reaction(PCR)were used to screen and confirm the presence of liver-specific genes.Apoa4-Cre rats and Cyp2c11-Cre rats were produced by CRISPR/Cas9 knockin.Rosa26-imCherry rats were employed to hybridize with the Cre rats to obtain the Apoa4-Cre/Rosa26-imCherry and Cyp2c11-Cre/Rosa26-imCherry rats.The temporal and spatial patterns of Cre expression were determined by the observation of red fluorescence on tis-sue sections.Hematoxylin-eosin stain was used to evaluate the liver histopathologic changes.The blood biochemical analysis of several liver enzymes and liver lipid profile was performed to evaluate the liver function of Cre rats.Results:Apoa4 and Cyp2c11 were identified as two liver-specific genes.Apoa4-Cre and Cyp2c11-Cre rats were produced and hybridized with Rosa26-imCherry rats.The red fluorescence indicated that the Cre recombinases were specially expressed in the juvenile and adult liver and not in other organs of two hybridized rats.All the blood biochemical parameters except low-density lipoprotein(LDL)did not change signifi-cantly in the Cre rats.No histological alterations were detected in the livers of the Cre rats.Conclusions:Liver-specific Apoa4-Cre and Cyp2c11-Cre rats have been established successfully and could be used to study gene knockout,specifically in juvenile and adult liver.展开更多
Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods...Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations （10, 100, and 500 nmol/L）. Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.展开更多
An approach was proposed to specify the C4ISR capability of domain-specific modeling language.To confine the domain modeling within a standard architecture framework,formally a C4ISR capability meta-ontology was defin...An approach was proposed to specify the C4ISR capability of domain-specific modeling language.To confine the domain modeling within a standard architecture framework,formally a C4ISR capability meta-ontology was defined according to the meta-model of DoD Architecture Framework.The meta-ontology is used for extending UML Profile so that the domain experts can model the C4ISR domains using the C4ISR capability meta-concepts to define a domain-specific modeling language.The domain models can be then checked to guarantee the consistency and completeness through converting the UML models into the Description Logic ontology and making use of inference engine Pellet to verify the ontology.展开更多
目的探究联系-概念-实用练习-总结(connections-concepts-concrete practice-conclusions,4C)教学法联合案例教学法(case-based learning,CBL)在泌尿外科护理实习带教中的应用效果。方法回顾性选取2022年5月—2023年4月于郑州大学第一...目的探究联系-概念-实用练习-总结(connections-concepts-concrete practice-conclusions,4C)教学法联合案例教学法(case-based learning,CBL)在泌尿外科护理实习带教中的应用效果。方法回顾性选取2022年5月—2023年4月于郑州大学第一附属医院泌尿外科实习的118名护理实习生(简称护生)为研究对象,依据不同带教方式分为对照组(n=58)、观察组(n=60)。对照组接受常规带教实习,观察组在对照组的基础上接受4C教学法联合CBL教学法,实习6个月。对比2组出科成绩、中文版医患沟通技能评价量表(set the stage,elicit information,give information,understand the patient's perspective,end the encounter,SEGUE)、注册护士核心能力量表(competency inventory for registered nurses,CIRN)、自我导向学习量表(self-rating scale of self-directed learning,SRSSDL)评分及护生满意度。结果观察组理论知识、实操技能评分[(90.45±4.25)分、(91.57±3.77)分]均高于对照组[(83.67±6.91)分、(80.64±6.38)分],差异有统计学意义(P<0.001);观察组的SEGUE、CIRN、SRSSDL量表各项评分均高于对照组,差异有统计学意义(P<0.05);观察组护生满意度(96.67%)高于对照组(81.03%),差异有统计学意义(P<0.05)。结论4C教学法联合CBL教学法应用于泌尿外科护理实习带教中可提升护生核心能力及医患沟通能力,还能增强自我导向学习能力,提高出科成绩,增强满意度。展开更多
基金CAMS Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2021-I2M-1-035National Natural Science Foundation of China,Grant/Award Number:31970508。
文摘Background:Liver diseases are a major contributor to both morbidity and mortality.Conditional knockout animals are always produced through crossing floxed animals with a tissue-specific Cre animal.The use of floxed rat resource has rapidly increased,but the liver-specific Cre rat lines for studying liver diseases and interested genes are limited,especially in a spatially and temporally restricted manner.Methods:RNA sequencing and real-time polymerase chain reaction(PCR)were used to screen and confirm the presence of liver-specific genes.Apoa4-Cre rats and Cyp2c11-Cre rats were produced by CRISPR/Cas9 knockin.Rosa26-imCherry rats were employed to hybridize with the Cre rats to obtain the Apoa4-Cre/Rosa26-imCherry and Cyp2c11-Cre/Rosa26-imCherry rats.The temporal and spatial patterns of Cre expression were determined by the observation of red fluorescence on tis-sue sections.Hematoxylin-eosin stain was used to evaluate the liver histopathologic changes.The blood biochemical analysis of several liver enzymes and liver lipid profile was performed to evaluate the liver function of Cre rats.Results:Apoa4 and Cyp2c11 were identified as two liver-specific genes.Apoa4-Cre and Cyp2c11-Cre rats were produced and hybridized with Rosa26-imCherry rats.The red fluorescence indicated that the Cre recombinases were specially expressed in the juvenile and adult liver and not in other organs of two hybridized rats.All the blood biochemical parameters except low-density lipoprotein(LDL)did not change signifi-cantly in the Cre rats.No histological alterations were detected in the livers of the Cre rats.Conclusions:Liver-specific Apoa4-Cre and Cyp2c11-Cre rats have been established successfully and could be used to study gene knockout,specifically in juvenile and adult liver.
基金supported by grants from the National Basic Research Development Program of China (2010CB529806)the National Natural Science Foundation of China (31171064)+1 种基金the Key Research Program of Science and Technology Commissions of Shanghai Municipality (11JC1404300)the Leading Academic Discipline Project of Shanghai Municipal Education Commission (J50108)
文摘Objective In this study, the pharmacological kinetics of Buthus martensi Karsch （BmK） AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes. Methods Two-electrode voltage clamp was used to record the whole-cell sodium current. Results The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations （10, 100, and 500 nmol/L）. Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations. Conclusion This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.
基金Project(2007AA01Z126) supported by the National High Technology Research and Development Program of ChinaProject(51306010202) supported by the National Defense Advance Research Program of China
文摘An approach was proposed to specify the C4ISR capability of domain-specific modeling language.To confine the domain modeling within a standard architecture framework,formally a C4ISR capability meta-ontology was defined according to the meta-model of DoD Architecture Framework.The meta-ontology is used for extending UML Profile so that the domain experts can model the C4ISR domains using the C4ISR capability meta-concepts to define a domain-specific modeling language.The domain models can be then checked to guarantee the consistency and completeness through converting the UML models into the Description Logic ontology and making use of inference engine Pellet to verify the ontology.
文摘目的探究联系-概念-实用练习-总结(connections-concepts-concrete practice-conclusions,4C)教学法联合案例教学法(case-based learning,CBL)在泌尿外科护理实习带教中的应用效果。方法回顾性选取2022年5月—2023年4月于郑州大学第一附属医院泌尿外科实习的118名护理实习生(简称护生)为研究对象,依据不同带教方式分为对照组(n=58)、观察组(n=60)。对照组接受常规带教实习,观察组在对照组的基础上接受4C教学法联合CBL教学法,实习6个月。对比2组出科成绩、中文版医患沟通技能评价量表(set the stage,elicit information,give information,understand the patient's perspective,end the encounter,SEGUE)、注册护士核心能力量表(competency inventory for registered nurses,CIRN)、自我导向学习量表(self-rating scale of self-directed learning,SRSSDL)评分及护生满意度。结果观察组理论知识、实操技能评分[(90.45±4.25)分、(91.57±3.77)分]均高于对照组[(83.67±6.91)分、(80.64±6.38)分],差异有统计学意义(P<0.001);观察组的SEGUE、CIRN、SRSSDL量表各项评分均高于对照组,差异有统计学意义(P<0.05);观察组护生满意度(96.67%)高于对照组(81.03%),差异有统计学意义(P<0.05)。结论4C教学法联合CBL教学法应用于泌尿外科护理实习带教中可提升护生核心能力及医患沟通能力,还能增强自我导向学习能力,提高出科成绩,增强满意度。
