This paper studies the evolutionary process of cooperative behavior in a public goods game model with heterogeneous investment strategies in square lattices.In the proposed model,players are divided into defectors,coo...This paper studies the evolutionary process of cooperative behavior in a public goods game model with heterogeneous investment strategies in square lattices.In the proposed model,players are divided into defectors,cooperators and discreet investors.Among these,defectors do not participate in investing,discreet investors make heterogeneous investments based on the investment behavior and cooperation value of their neighbors,and cooperators invest equally in each neighbor.In real life,heterogeneous investment is often accompanied by time or economic costs.The discreet investors in this paper pay a certain price to obtain their neighbors'investment behavior and cooperation value,which quantifies the time and economic costs of the heterogeneous investment process.The results of Monte Carlo simulation experiments in this study show that discreet investors can effectively resist the invasion of the defectors,form a stable cooperative group and expand the cooperative advantage in evolution.However,when discreet investors pay too high a price,they lose their strategic advantage.The results in this paper help us understand the role of heterogeneous investment in promoting and maintaining human social cooperation.展开更多
In the realm of public goods game,punishment,as a potent tool,stands out for fostering cooperation.While it effectively addresses the first-order free-rider problem,the associated costs can be substantial.Punishers in...In the realm of public goods game,punishment,as a potent tool,stands out for fostering cooperation.While it effectively addresses the first-order free-rider problem,the associated costs can be substantial.Punishers incur expenses in imposing sanctions,while defectors face fines.Unfortunately,these monetary elements seemingly vanish into thin air,representing a loss to the system itself.However,by virtue of the redistribution of fines to cooperators and punishers,not only can we mitigate this loss,but the rewards for these cooperative individuals can be enhanced.Based upon this premise,this paper introduces a fine distribution mechanism to the traditional pool punishment model.Under identical parameter settings,by conducting a comparative experiment with the conventional punishment model,the paper aims to investigate the impact of fine distribution on the evolution of cooperation in spatial public goods game.The experimental results clearly demonstrate that,in instances where the punishment cost is prohibitively high,the cooperative strategies of the traditional pool punishment model may completely collapse.However,the model enriched with fine distribution manages to sustain a considerable number of cooperative strategies,thus highlighting its effectiveness in promoting and preserving cooperation,even in the face of substantial punishment cost.展开更多
A multi-strategy hybrid whale optimization algorithm(MSHWOA)for complex constrained optimization problems is proposed to overcome the drawbacks of easily trapping into local optimum,slow convergence speed and low opti...A multi-strategy hybrid whale optimization algorithm(MSHWOA)for complex constrained optimization problems is proposed to overcome the drawbacks of easily trapping into local optimum,slow convergence speed and low optimization precision.Firstly,the population is initialized by introducing the theory of good point set,which increases the randomness and diversity of the population and lays the foundation for the global optimization of the algorithm.Then,a novel linearly update equation of convergence factor is designed to coordinate the abilities of exploration and exploitation.At the same time,the global exploration and local exploitation capabilities are improved through the siege mechanism of Harris Hawks optimization algorithm.Finally,the simulation experiments are conducted on the 6 benchmark functions and Wilcoxon rank sum test to evaluate the optimization performance of the improved algorithm.The experimental results show that the proposed algorithm has more significant improvement in optimization accuracy,convergence speed and robustness than the comparison algorithm.展开更多
Objective:To evaluate relationship between changes in the beneficial bacteria in intensive care unit(ICU)patients and nutritional therapy type.Methods:Ten patients aged≥18 years admitted to the ICU between January an...Objective:To evaluate relationship between changes in the beneficial bacteria in intensive care unit(ICU)patients and nutritional therapy type.Methods:Ten patients aged≥18 years admitted to the ICU between January and December 2020,were included.Good enteral nutrition was defined as early achievement of target calorie intake through enteral feeding.The ratio of beneficial bacteria at the first and second bowel movements after each patient’s admission was calculated and the patients were classified into the increase or decrease group.Among all patients,five each were in the increase and decrease groups.We investigated patient background,changes in sequential organ failure assessment(SOFA)and acute physiology and chronic health evaluation(APACHE)Ⅱscores,nutritional doses or methods,and clinical outcomes.Results:No relationship was found between changes in the ratio of beneficial bacteria and changes in SOFA/APACHEⅡscores at the time of admission.The rate of good enteral nutrition was significantly higher in the increase group than in the decrease group(4/5 vs.0/5,P=0.01).Conclusions:An increase in beneficial bacteria may be significantly related to the early establishment of enteral nutrition.In the future,accumulating cases may make it possible to establish a new nutritional strategy for critically ill patients from an intestinal microbiota perspective.展开更多
With the deepening of Internet technology in international trade,cross-border e-commerce has become the main incremental contributor in the import and export trade of goods,and its transaction volume has gradually inc...With the deepening of Internet technology in international trade,cross-border e-commerce has become the main incremental contributor in the import and export trade of goods,and its transaction volume has gradually increased from 16%of China’s total import and export of goods in 2014 to 42%in 2023.展开更多
Exerting the leading role of standards is very important for achieving the high-quality development. In recent years, China has unceasingly improved the mandatory national standards for energy efficiency and safety of...Exerting the leading role of standards is very important for achieving the high-quality development. In recent years, China has unceasingly improved the mandatory national standards for energy efficiency and safety of products, expedited the development and revision of standards in the areas of digital, intelligent, green and low-carbon development, and led the continuous technological upgrading of industrial and consumer goods.展开更多
BACKGROUND Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.However,the underlying mechanisms remain elusive.AIM To detect the dif...BACKGROUND Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.However,the underlying mechanisms remain elusive.AIM To detect the differential expression profiles of plasma exosomal microRNAs(miRNAs)in poor and good responders and explore the potential mechanisms of chemoresistance.METHODS In this study,the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses(poor/good responders)and treatment courses(pre/post-nCRT)using RNA sequencing.RESULTS Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT.Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways,such as the MAPK signaling pathway,EGFR tyrosine kinase inhibitor resistance,Toll-like receptor signaling pathway,VEGF signaling pathway,and mTOR signaling pathway.Further analysis indicated that MAPK3,RAX2,and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer,and the profiles of MAPK3,TSPYL5,and ZNF-417 were correlated with tumor stage.In addition,the expression profiles of MAPK3,RNF165,and ZNF417 were negatively correlated with inhibitory concentration 50 values.Accordingly,an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.CONCLUSION This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs.However,further research is required within the framework of our established miRNA-mRNA network.展开更多
Recently released economic data reflecting China’s brisk economic activities and vibrant foreign trade attest to a steady acceleration in the country’s economic growth.The National Bureau of Statistics(NBS)reported ...Recently released economic data reflecting China’s brisk economic activities and vibrant foreign trade attest to a steady acceleration in the country’s economic growth.The National Bureau of Statistics(NBS)reported 5.5 percent year-on-year growth during the first two months of 2024 for retail sales of consumer goods,4.2 percent for fixed-asset investment,and 7 percent for value-added of the industrial enterprises above the designated size.The country’s total import and export of goods,meanwhile,expanded 8.7 percent year-on-year,and its volume for this period achieved a historical high of RMB 6.61 trillion.展开更多
Aristotle related both dependent variables:democratization and autocratization in his broader explanation of regime change.For him two factors were crucial,the number of rulers(one,a few,the masses)and their values an...Aristotle related both dependent variables:democratization and autocratization in his broader explanation of regime change.For him two factors were crucial,the number of rulers(one,a few,the masses)and their values and behavior in terms of normal times and in crises periods.Here we try to be as parsimonious as possible emphasizing the size of the selectorate,as Aristotle knew already.The selectorate comprises the people who have a say in selecting political leaders.In this respect selectorate theory(Bueno de Mesquita et al.)is purely formal and helps to explain both,the origins of democracy and autocracy as well as their dismissal.The size of the selectorate is the crucial intervening variable in linking more specific causes and circumstances for bringing about the respective states on the dependent variables.Other theoretical glimpses will be taken at crises of democracies and autocracies.The size of the electorate can be limited by(brute)force or even through abstaining from the right to vote or using it to abolish democracy for autocracy(Przeworski,Zimmermann,and Saalfeld).Here we emphasize four major blocs of variables:(1)economic success(Lipset,Huntington),(2)the relative size of the consenters,dissenters,and assenters(Easton,Wright,Linz)bolstering even badly performing democratic and autocratic regimes,(3)the exit options and alternatives created for and by political and economic elites,possibly tied to potential mass mobilization and protest action,and(4)democratic peace theory as to external challenges to regime change.A causal model will be developed around those factors hopefully bringing about a consistent understanding of the basic processes of democratization and autocratization.展开更多
Flannery O’Connor is one of the representative figures of American Southern writers.Being recognized as the most outstanding writer of the American South after Faulkner,she has great influence in the literary world.H...Flannery O’Connor is one of the representative figures of American Southern writers.Being recognized as the most outstanding writer of the American South after Faulkner,she has great influence in the literary world.Her works are always shrouded in a strange and grotesque atmosphere and full of death as well as religious metaphors.The protagonists are a series of American Southern freaks struggling with the crisis of spiritual belief.The protagonists of her novel A Good Man is Hard to Find are a hypocritical believer in the world of sinners and a lost man suffering in the midst of real sin,thus O’Connor uses the highest form of violence-death to bring ultimate redemption to them.In people’s conception,violence and redemption are often opposite to each other,but O’Connor uses bloody and violent plots to explore the theme of religious salvation,integrating and unifying the two contrary concepts to form her unique and profound violent redemption writing.展开更多
Since the Harris-Todaro model was proposed in 1970,it has played a crucial role in analyzing various environmental and trade issues in developing countries.This paper analyzes the effects of the amount of public inter...Since the Harris-Todaro model was proposed in 1970,it has played a crucial role in analyzing various environmental and trade issues in developing countries.This paper analyzes the effects of the amount of public intermediate goods provided by the government,the increase in the fixed wage rate in the urban sector,and the changes in the relative international prices of agricultural and manufacturing goods on labor employment,unemployment,and the economic welfare in the context of a small open economy.It also proposes relevant policies to reduce the unemployment rate while improving national welfare.展开更多
Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature...Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.展开更多
Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the m...Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the multinational pharmaceutical companies were analyzed based on the requirements of regulations and laws.Results and Conclusion There are some gaps between local and multinational pharmaceutical companies in the construction of pharmacovigilance system.We can learn from the experience of multinational pharmaceutical companies to improve the pharmacovigilance system,which includes building a sound pharmacovigilance organizational structure,establishing a series of operational system files and cultivating professional talents.MAHs of China should improve the structure of enterprise pharmacovigilance system.Besides,members of Drug Safety Committee should be department managers with higher position so that they can fulfil the responsibilities of risk assessment.If MAHs possess a large variety and quantity of products,a Drug Safety Committee should be established to ensure the timely discovery of risks.In addition,MAHs should pay attention to the implementation of related regulations and laws on pharmacovigilance and establish compliant,effective and operatable files combing with the actual operation of pharmacovigilance system.Finally,MAHs should introduce and train pharmacovigilance talents,and hire pharmacovigilance experts as consultants to solve the problem of talent shortage.展开更多
Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential b...Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.展开更多
The Asia-Pacific Economic Cooperation(APEC)is contemplating expanding its list of environmental goods(EG)for trade liberalization to fight climate change.In support of doing so,this study proposes that a long list tha...The Asia-Pacific Economic Cooperation(APEC)is contemplating expanding its list of environmental goods(EG)for trade liberalization to fight climate change.In support of doing so,this study proposes that a long list that retains controversies is better for carbon emission reduction than a short common list.This study examines four mechanisms of longer lists:enlarging market scales,enriching product mixes,enhancing product sophistication,and enriching trade patterns.Using China’s emerging EG trade during the 2001-2015 period as a case study,this study compares four EG lists with different EG.The results show that:(1)a longer list reduces carbon emissions from both imports and exports,making domestic regions with different advantages have better chances of improving carbon efficiencies.(2)Product sophistication reduces the emission gap between trading partners,regardless of the length of EG lists.(3)China’s EG exports contribute to carbon reduction in leading regions,while EG imports provide laggard regions with better chances of reducing carbon emissions.These findings provide three implications for future list-making:it is important to(1)seek a long and inclusive list rather than a short common list,(2)shift the focus from environmental end-use to the technological contents of products,and(3)balance the demand of laggard regions to import and the capacity of leading regions to export.展开更多
基金Project supported by the Open Foundation of Key Laboratory of Software Engineering of Yunnan Province(Grant Nos.2020SE308 and 2020SE309).
文摘This paper studies the evolutionary process of cooperative behavior in a public goods game model with heterogeneous investment strategies in square lattices.In the proposed model,players are divided into defectors,cooperators and discreet investors.Among these,defectors do not participate in investing,discreet investors make heterogeneous investments based on the investment behavior and cooperation value of their neighbors,and cooperators invest equally in each neighbor.In real life,heterogeneous investment is often accompanied by time or economic costs.The discreet investors in this paper pay a certain price to obtain their neighbors'investment behavior and cooperation value,which quantifies the time and economic costs of the heterogeneous investment process.The results of Monte Carlo simulation experiments in this study show that discreet investors can effectively resist the invasion of the defectors,form a stable cooperative group and expand the cooperative advantage in evolution.However,when discreet investors pay too high a price,they lose their strategic advantage.The results in this paper help us understand the role of heterogeneous investment in promoting and maintaining human social cooperation.
基金the Open Foundation of Key Lab-oratory of Software Engineering of Yunnan Province(Grant Nos.2020SE308 and 2020SE309).
文摘In the realm of public goods game,punishment,as a potent tool,stands out for fostering cooperation.While it effectively addresses the first-order free-rider problem,the associated costs can be substantial.Punishers incur expenses in imposing sanctions,while defectors face fines.Unfortunately,these monetary elements seemingly vanish into thin air,representing a loss to the system itself.However,by virtue of the redistribution of fines to cooperators and punishers,not only can we mitigate this loss,but the rewards for these cooperative individuals can be enhanced.Based upon this premise,this paper introduces a fine distribution mechanism to the traditional pool punishment model.Under identical parameter settings,by conducting a comparative experiment with the conventional punishment model,the paper aims to investigate the impact of fine distribution on the evolution of cooperation in spatial public goods game.The experimental results clearly demonstrate that,in instances where the punishment cost is prohibitively high,the cooperative strategies of the traditional pool punishment model may completely collapse.However,the model enriched with fine distribution manages to sustain a considerable number of cooperative strategies,thus highlighting its effectiveness in promoting and preserving cooperation,even in the face of substantial punishment cost.
基金the National Natural Science Foundation of China(No.62176146)。
文摘A multi-strategy hybrid whale optimization algorithm(MSHWOA)for complex constrained optimization problems is proposed to overcome the drawbacks of easily trapping into local optimum,slow convergence speed and low optimization precision.Firstly,the population is initialized by introducing the theory of good point set,which increases the randomness and diversity of the population and lays the foundation for the global optimization of the algorithm.Then,a novel linearly update equation of convergence factor is designed to coordinate the abilities of exploration and exploitation.At the same time,the global exploration and local exploitation capabilities are improved through the siege mechanism of Harris Hawks optimization algorithm.Finally,the simulation experiments are conducted on the 6 benchmark functions and Wilcoxon rank sum test to evaluate the optimization performance of the improved algorithm.The experimental results show that the proposed algorithm has more significant improvement in optimization accuracy,convergence speed and robustness than the comparison algorithm.
文摘Objective:To evaluate relationship between changes in the beneficial bacteria in intensive care unit(ICU)patients and nutritional therapy type.Methods:Ten patients aged≥18 years admitted to the ICU between January and December 2020,were included.Good enteral nutrition was defined as early achievement of target calorie intake through enteral feeding.The ratio of beneficial bacteria at the first and second bowel movements after each patient’s admission was calculated and the patients were classified into the increase or decrease group.Among all patients,five each were in the increase and decrease groups.We investigated patient background,changes in sequential organ failure assessment(SOFA)and acute physiology and chronic health evaluation(APACHE)Ⅱscores,nutritional doses or methods,and clinical outcomes.Results:No relationship was found between changes in the ratio of beneficial bacteria and changes in SOFA/APACHEⅡscores at the time of admission.The rate of good enteral nutrition was significantly higher in the increase group than in the decrease group(4/5 vs.0/5,P=0.01).Conclusions:An increase in beneficial bacteria may be significantly related to the early establishment of enteral nutrition.In the future,accumulating cases may make it possible to establish a new nutritional strategy for critically ill patients from an intestinal microbiota perspective.
文摘With the deepening of Internet technology in international trade,cross-border e-commerce has become the main incremental contributor in the import and export trade of goods,and its transaction volume has gradually increased from 16%of China’s total import and export of goods in 2014 to 42%in 2023.
文摘Exerting the leading role of standards is very important for achieving the high-quality development. In recent years, China has unceasingly improved the mandatory national standards for energy efficiency and safety of products, expedited the development and revision of standards in the areas of digital, intelligent, green and low-carbon development, and led the continuous technological upgrading of industrial and consumer goods.
基金Supported by the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-C-005.
文摘BACKGROUND Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.However,the underlying mechanisms remain elusive.AIM To detect the differential expression profiles of plasma exosomal microRNAs(miRNAs)in poor and good responders and explore the potential mechanisms of chemoresistance.METHODS In this study,the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses(poor/good responders)and treatment courses(pre/post-nCRT)using RNA sequencing.RESULTS Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT.Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways,such as the MAPK signaling pathway,EGFR tyrosine kinase inhibitor resistance,Toll-like receptor signaling pathway,VEGF signaling pathway,and mTOR signaling pathway.Further analysis indicated that MAPK3,RAX2,and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer,and the profiles of MAPK3,TSPYL5,and ZNF-417 were correlated with tumor stage.In addition,the expression profiles of MAPK3,RNF165,and ZNF417 were negatively correlated with inhibitory concentration 50 values.Accordingly,an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.CONCLUSION This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs.However,further research is required within the framework of our established miRNA-mRNA network.
文摘Recently released economic data reflecting China’s brisk economic activities and vibrant foreign trade attest to a steady acceleration in the country’s economic growth.The National Bureau of Statistics(NBS)reported 5.5 percent year-on-year growth during the first two months of 2024 for retail sales of consumer goods,4.2 percent for fixed-asset investment,and 7 percent for value-added of the industrial enterprises above the designated size.The country’s total import and export of goods,meanwhile,expanded 8.7 percent year-on-year,and its volume for this period achieved a historical high of RMB 6.61 trillion.
文摘Aristotle related both dependent variables:democratization and autocratization in his broader explanation of regime change.For him two factors were crucial,the number of rulers(one,a few,the masses)and their values and behavior in terms of normal times and in crises periods.Here we try to be as parsimonious as possible emphasizing the size of the selectorate,as Aristotle knew already.The selectorate comprises the people who have a say in selecting political leaders.In this respect selectorate theory(Bueno de Mesquita et al.)is purely formal and helps to explain both,the origins of democracy and autocracy as well as their dismissal.The size of the selectorate is the crucial intervening variable in linking more specific causes and circumstances for bringing about the respective states on the dependent variables.Other theoretical glimpses will be taken at crises of democracies and autocracies.The size of the electorate can be limited by(brute)force or even through abstaining from the right to vote or using it to abolish democracy for autocracy(Przeworski,Zimmermann,and Saalfeld).Here we emphasize four major blocs of variables:(1)economic success(Lipset,Huntington),(2)the relative size of the consenters,dissenters,and assenters(Easton,Wright,Linz)bolstering even badly performing democratic and autocratic regimes,(3)the exit options and alternatives created for and by political and economic elites,possibly tied to potential mass mobilization and protest action,and(4)democratic peace theory as to external challenges to regime change.A causal model will be developed around those factors hopefully bringing about a consistent understanding of the basic processes of democratization and autocratization.
文摘Flannery O’Connor is one of the representative figures of American Southern writers.Being recognized as the most outstanding writer of the American South after Faulkner,she has great influence in the literary world.Her works are always shrouded in a strange and grotesque atmosphere and full of death as well as religious metaphors.The protagonists are a series of American Southern freaks struggling with the crisis of spiritual belief.The protagonists of her novel A Good Man is Hard to Find are a hypocritical believer in the world of sinners and a lost man suffering in the midst of real sin,thus O’Connor uses the highest form of violence-death to bring ultimate redemption to them.In people’s conception,violence and redemption are often opposite to each other,but O’Connor uses bloody and violent plots to explore the theme of religious salvation,integrating and unifying the two contrary concepts to form her unique and profound violent redemption writing.
文摘Since the Harris-Todaro model was proposed in 1970,it has played a crucial role in analyzing various environmental and trade issues in developing countries.This paper analyzes the effects of the amount of public intermediate goods provided by the government,the increase in the fixed wage rate in the urban sector,and the changes in the relative international prices of agricultural and manufacturing goods on labor employment,unemployment,and the economic welfare in the context of a small open economy.It also proposes relevant policies to reduce the unemployment rate while improving national welfare.
文摘Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.
基金Integration Application Status and Problems Investigation of ICH Q8,Q9,Q10 across the Product Life Cycle(No.20210605).
文摘Objective To provide suggestions for helping marketing authorization holders(MAHs)to develop an effective and compliant pharmacovigilance system.Methods The construction strategies of pharmacovigilance system of the multinational pharmaceutical companies were analyzed based on the requirements of regulations and laws.Results and Conclusion There are some gaps between local and multinational pharmaceutical companies in the construction of pharmacovigilance system.We can learn from the experience of multinational pharmaceutical companies to improve the pharmacovigilance system,which includes building a sound pharmacovigilance organizational structure,establishing a series of operational system files and cultivating professional talents.MAHs of China should improve the structure of enterprise pharmacovigilance system.Besides,members of Drug Safety Committee should be department managers with higher position so that they can fulfil the responsibilities of risk assessment.If MAHs possess a large variety and quantity of products,a Drug Safety Committee should be established to ensure the timely discovery of risks.In addition,MAHs should pay attention to the implementation of related regulations and laws on pharmacovigilance and establish compliant,effective and operatable files combing with the actual operation of pharmacovigilance system.Finally,MAHs should introduce and train pharmacovigilance talents,and hire pharmacovigilance experts as consultants to solve the problem of talent shortage.
基金The research was funded by the National Natural Science Foundation of China(Grant Nos.:82171973,82171980,and 82102092)Beijing Millions of Talent Projects A Level Funding(Grant No.:2019A38)+2 种基金The study was also supported by Beijing Hospitals Authority Dengfeng Project(Grant No.:DFL20191102)the Pilot Project(4th Round)to Reform Public Development of Beijing Municipal Medical Research Institute(20211)the Third Foster Plan in 2019“Molecular Imaging Probe Preparation and Characterization of Key Technologies and Equipment”for the Development of Key Technologies and Equipment in Major Science and Technology Infrastructure in Shenzhen,China.
文摘Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-^(89)(^(89)Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[^(89)Zr]Zr-desferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,>99%)and specific activity(24.15±1.34 GBq/mmol),and was stable in 5%human serum albumin,and phosphate buffer saline(>85%RCP at 96 h).The EC_(50) values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P>0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[^(89)Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2().The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16%ID/g)than BGC823 mice(0.69±0.02%ID/g)and blocking group(0.72±0.02%ID/g).A dosimetry estimation study showed that the effective dose of[^(89)Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these results suggest that Good Manufacturing Practices produced by this immuno-positron emission tomography probe can detect CLDN18.2-overexpressing tumors.
基金supported by the National Natural Science Foundation of China(Grants No.42271178 and 41801104).
文摘The Asia-Pacific Economic Cooperation(APEC)is contemplating expanding its list of environmental goods(EG)for trade liberalization to fight climate change.In support of doing so,this study proposes that a long list that retains controversies is better for carbon emission reduction than a short common list.This study examines four mechanisms of longer lists:enlarging market scales,enriching product mixes,enhancing product sophistication,and enriching trade patterns.Using China’s emerging EG trade during the 2001-2015 period as a case study,this study compares four EG lists with different EG.The results show that:(1)a longer list reduces carbon emissions from both imports and exports,making domestic regions with different advantages have better chances of improving carbon efficiencies.(2)Product sophistication reduces the emission gap between trading partners,regardless of the length of EG lists.(3)China’s EG exports contribute to carbon reduction in leading regions,while EG imports provide laggard regions with better chances of reducing carbon emissions.These findings provide three implications for future list-making:it is important to(1)seek a long and inclusive list rather than a short common list,(2)shift the focus from environmental end-use to the technological contents of products,and(3)balance the demand of laggard regions to import and the capacity of leading regions to export.
