Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly ...Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).展开更多
This paper introduces the system structure and work principle of the upgraded real time information system in Wangting Power Plant, and then expounds the realization way and function features of this system on B/S co...This paper introduces the system structure and work principle of the upgraded real time information system in Wangting Power Plant, and then expounds the realization way and function features of this system on B/S computing mode. The results of field application show the new system has good capability, reliability and expandability.展开更多
目的探析脑梗死患者髓鞘碱性蛋白(myelin basic protein,MBP)、S100钙结合蛋白B(S100 calcium-binding protein B,S100-B)水平与介入治疗后早期神经功能恶化的关联性。方法纳入2021年7月–2024年7月期间本院收治的258例脑梗死患者,采用...目的探析脑梗死患者髓鞘碱性蛋白(myelin basic protein,MBP)、S100钙结合蛋白B(S100 calcium-binding protein B,S100-B)水平与介入治疗后早期神经功能恶化的关联性。方法纳入2021年7月–2024年7月期间本院收治的258例脑梗死患者,采用美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分评估患者的神经功能状况,将死亡患者或介入治疗24 h后NIHSS评分增加4分及以上患者纳入早期神经功能恶化组,其余患者纳入未恶化组。测定所有患者MBP、S100-B水平,并分析其水平变化与介入治疗后神经功能恶化风险的关系。结果脑梗死患者早期神经功能恶化组血清MBP、S100-B水平高于未恶化组〔t=9.062(95%CI:2.348~3.663)、7.708(95%CI:0.221~0.375),P<0.001〕;Spearman相关性显示:恶化组血清MBP、S100-B水平与NIHSS评分增加情况呈正相关〔r=0.323(95%CI:0.095~0.542)、0.292(95%CI:0.066~0.488),P<0.05〕;分层回归分析显示:血清MBP〔比值比(odds ratio,OR)=1.996,95%CI:1.607~2.478〕、S100-B(OR=1.005,95%CI:1.003~1.007)水平是影响脑梗死患者早期神经功能恶化的危险因素(P<0.05),即使校正混杂因素后依然是其危险因素,此外入院NIHSS评分(OR=1.224,95%CI:1.142~1.310)及合并高血压(OR=2.542,95%CI:1.139~5.669)、高脂血症(OR=2.618,95%CI:1.101~6.228),其中入院NIHSS评分与MBP存在交互作用(OR=1.081,95%CI:1.034~1.130);受试者工作特征曲线显示:血清MBP、S100-B水平评估脑梗死患者早期神经功能恶化的曲线下面积分别为0.822(95%CI:0.764~0.879)、0.788(95%CI:0.724~0.853)。结论脑梗死患者介入治疗后血清MBP、S100-B水平较高与早期神经功能恶化风险相关,且对神经功能恶化风险有一定的评估价值。展开更多
目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料...目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料和血清HMGB1、S100β水平及24 h BIS,分析脓毒症病人发生SAE的影响因素和HMGB1、S100β、BIS联合检测早期诊断SAE的临床价值。结果:SAE组病人APACHEⅡ评分、SOFA评分均明显高于非SAE组(P<0.01);SAE组血清HMGB1、S100β水平均明显高于非SAE组(P<0.01),而BIS明显低于非SAE组(P<0.01)。APACHEⅡ评分、SOFA评分和HMGB1、S100β、BIS均为脓毒症病人发生SAE的独立影响因素(P<0.01)。ROC曲线分析显示,血清HMGB1、S100β联合BIS早期诊断脓毒症病人发生SAE的AUC为0.891,敏感度为91.43%,特异度为84.62%,优于各指标独立诊断。结论:血清HMGB1、S100β联合BIS在SAE早期诊断中具有较好的临床应用价值。展开更多
With the rapid development of modern technology and all-round reform in national college English teaching,Internet-Based teaching mode has become a new trend of college English teaching.Therefore,in the new teaching m...With the rapid development of modern technology and all-round reform in national college English teaching,Internet-Based teaching mode has become a new trend of college English teaching.Therefore,in the new teaching mode,the teacher should turn an inculcator into an instructor,facilitator and participant in teaching;a passive user of textbook into a dominant and modeler of courses;a planner of teaching specific tasks into an organizer of teaching process,a helper and shepherd of learning knowledge.展开更多
基金National Key R&D Program of China,Grant/Award Number:2023YFC3402000National Institutes for Food and Drug Control,State Key Laboratory of Drug Regulatory Science,Grant/Award Number:2023SKLDRS0124。
文摘Background:The precise insertion of large DNA fragments(>3–5 kb)remains one of the key obstacles in establishment of genetically modified murine models.Methods:A 21 kb large DNA fragment containing three tandemly linked copies of the human HRAS gene was inserted into the genome of C57BL/6J mouse,generating a mouse model designated as KI.C57-ras(or named NF-h HRAS).Whole-genome sequencing and Sanger sequencing were utilized to it confirm precise insertion and copy number.The stability of transgene expression among different generations was verified from multiple aspects using by digital PCR,western blot and DNA sequencing.To assess tumor susceptibility in the mouse model,N-Nitroso-N-methylurea(MNU)was administered at a dosage of 75 mg/kg.Histopathological examinations were conducted using hematoxylin and eosin(H&E)staining.Results:The HRAS DNA fragment was inserted into mouse chromosome 15E1 site,locating between 80623202 bp and 80625020 bp.NF-h HRAS mice exhibited stable inheritance and displayed consistent phenotypes across individuals.Moreover,this mouse model exhibited a high susceptibility to carcinogens.Upon administration of MNU the earliest mortality onset was earlier than that of wild-type littermates(day 65 vs.day 78 for male and day 56 vs.day 84 for female).Notably,100%of the NF-h HRAS transgenic mice developed tumors,with approximately 84%of male NF-h HRAS mice exhibiting specific tumor types,such as squamous cell carcinoma or squamous cell papilloma,which was consistent with the previously reported carcinogenic rasH2 mouse model.The types of tumors and the target organs exhibited diversity in NFh HRAS mice,while the spontaneous tumor incidence remained low(1/50).Conclusions:The NF-h HRAS mice demonstrated excellent genetic stability,a reproducible phenotype,and high susceptibility to carcinogens,indicating their potential utility in non-clinical safety evaluations of drugs as per the S1B guidelines issued by the ICH(The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use).
文摘This paper introduces the system structure and work principle of the upgraded real time information system in Wangting Power Plant, and then expounds the realization way and function features of this system on B/S computing mode. The results of field application show the new system has good capability, reliability and expandability.
文摘目的探析脑梗死患者髓鞘碱性蛋白(myelin basic protein,MBP)、S100钙结合蛋白B(S100 calcium-binding protein B,S100-B)水平与介入治疗后早期神经功能恶化的关联性。方法纳入2021年7月–2024年7月期间本院收治的258例脑梗死患者,采用美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分评估患者的神经功能状况,将死亡患者或介入治疗24 h后NIHSS评分增加4分及以上患者纳入早期神经功能恶化组,其余患者纳入未恶化组。测定所有患者MBP、S100-B水平,并分析其水平变化与介入治疗后神经功能恶化风险的关系。结果脑梗死患者早期神经功能恶化组血清MBP、S100-B水平高于未恶化组〔t=9.062(95%CI:2.348~3.663)、7.708(95%CI:0.221~0.375),P<0.001〕;Spearman相关性显示:恶化组血清MBP、S100-B水平与NIHSS评分增加情况呈正相关〔r=0.323(95%CI:0.095~0.542)、0.292(95%CI:0.066~0.488),P<0.05〕;分层回归分析显示:血清MBP〔比值比(odds ratio,OR)=1.996,95%CI:1.607~2.478〕、S100-B(OR=1.005,95%CI:1.003~1.007)水平是影响脑梗死患者早期神经功能恶化的危险因素(P<0.05),即使校正混杂因素后依然是其危险因素,此外入院NIHSS评分(OR=1.224,95%CI:1.142~1.310)及合并高血压(OR=2.542,95%CI:1.139~5.669)、高脂血症(OR=2.618,95%CI:1.101~6.228),其中入院NIHSS评分与MBP存在交互作用(OR=1.081,95%CI:1.034~1.130);受试者工作特征曲线显示:血清MBP、S100-B水平评估脑梗死患者早期神经功能恶化的曲线下面积分别为0.822(95%CI:0.764~0.879)、0.788(95%CI:0.724~0.853)。结论脑梗死患者介入治疗后血清MBP、S100-B水平较高与早期神经功能恶化风险相关,且对神经功能恶化风险有一定的评估价值。
文摘目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料和血清HMGB1、S100β水平及24 h BIS,分析脓毒症病人发生SAE的影响因素和HMGB1、S100β、BIS联合检测早期诊断SAE的临床价值。结果:SAE组病人APACHEⅡ评分、SOFA评分均明显高于非SAE组(P<0.01);SAE组血清HMGB1、S100β水平均明显高于非SAE组(P<0.01),而BIS明显低于非SAE组(P<0.01)。APACHEⅡ评分、SOFA评分和HMGB1、S100β、BIS均为脓毒症病人发生SAE的独立影响因素(P<0.01)。ROC曲线分析显示,血清HMGB1、S100β联合BIS早期诊断脓毒症病人发生SAE的AUC为0.891,敏感度为91.43%,特异度为84.62%,优于各指标独立诊断。结论:血清HMGB1、S100β联合BIS在SAE早期诊断中具有较好的临床应用价值。
文摘With the rapid development of modern technology and all-round reform in national college English teaching,Internet-Based teaching mode has become a new trend of college English teaching.Therefore,in the new teaching mode,the teacher should turn an inculcator into an instructor,facilitator and participant in teaching;a passive user of textbook into a dominant and modeler of courses;a planner of teaching specific tasks into an organizer of teaching process,a helper and shepherd of learning knowledge.
