Based on the data of the construction industry in Henan Province, China, from 2005 to 2020, the high-quality development level of the construction industry in Henan Province is measured. Firstly, this paper constructs...Based on the data of the construction industry in Henan Province, China, from 2005 to 2020, the high-quality development level of the construction industry in Henan Province is measured. Firstly, this paper constructs the indicator system based on the high-quality development theory and the characteristic of the construction industry from seven dimensions: industrial scale, industrial efficiency, industrial benefits, industrial innovation, industrial risk, industrial potential, and the green development of the construction industry. Secondly, using the global principal component analysis (PCA) method to measure the high-quality development level. Thirdly, cluster analysis is applied to measure the relative changes of various dimensions in different stages. The results show that overall the high-quality development level of the construction industry in Henan province is increasing, but different indicators perform differently in various stages, and the changes in real estate policies have a significant impact on this. Finally, based on these findings, we think it is better to reduce real estate dependence, promote the application of new materials and technologies and maintain the stability of real estate policies.展开更多
This paper analyzes the differences in geological and development characteristics between continental shale oil in China and marine shale oil in North America, reviews the evaluation methods and technological progress...This paper analyzes the differences in geological and development characteristics between continental shale oil in China and marine shale oil in North America, reviews the evaluation methods and technological progress of the continental shale oil development in China, and points out the existing problems and development directions of the continental shale oil development. The research progress of development evaluation technologies such as favorable lithofacies identification, reservoir characterization, mobility evaluation, fracability evaluation, productivity evaluation and geological-mathematical modeling integration are introduced. The efficient exploration and development of continental shale oil in China are faced with many problems, such as weak basic theoretical research, imperfect exploration and development technology system, big gap in engineering technology between China and other countries, and high development cost. Three key research issues must be studied in the future:(1) forming differentiated development technologies of continental shale oil through geological and engineering integrated research;(2) strengthening the application of big data and artificial intelligence to improve the accuracy of development evaluation;(3) tackling enhanced shale oil recovery technology and research effective development method, so as to improve the development effect and benefit.展开更多
This study aimed to develop a guideline for therapeutic drug monitoring(TDM) of vancomycin. We adopted the new guideline definition from the Institute of Medicine(IOM), adhered closely to the six domains of the Ap...This study aimed to develop a guideline for therapeutic drug monitoring(TDM) of vancomycin. We adopted the new guideline definition from the Institute of Medicine(IOM), adhered closely to the six domains of the Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ), and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome(PICO) and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation(GRADE).展开更多
Recreational fishery is the combination of traditional fishery and modern leisure activities.Development of recreational fishery resources must be based on related resources,but the present research on recreational fi...Recreational fishery is the combination of traditional fishery and modern leisure activities.Development of recreational fishery resources must be based on related resources,but the present research on recreational fishery is mainly confined to the development of leisure projects,the definition of connotation and scope of recreational fishery resources is rather vague,and there is no precise classification and evaluation system.According to the resources attributes,resources functions,and tourism resources classification,investigation and evaluation standard,recreational fishery resources include a number of different types.Expert Scoring Method and Analytic Hierarchy Process can be used to determine the evaluation factors of recreational fishery resources and their weights,and then make comprehensive evaluation on recreational fishery resources of different regions and types,so as to improve the scientific nature of recreational fishery development.展开更多
Rural revitalization strategy is an important strategic layout of rural development in the new era of the CPC Central Committee,and scientific and reasonable determination of village types is an important measure to p...Rural revitalization strategy is an important strategic layout of rural development in the new era of the CPC Central Committee,and scientific and reasonable determination of village types is an important measure to promote rural revitalization by classification.The villages of Wan’an County were selected as the research object.Firstly,the factors that have a key impact on the development of the villages were extracted and qualitatively analyzed to preliminarily screen and judge their types.Secondly,the evaluation index system of development potential of the villages was constructed to quantitatively evaluate and reasonably classify the villages.Finally,the spatial distribution characteristics and quantity of different villages were revealed,and differentiated development strategies were proposed.展开更多
Tong's B-type water drive method was proposed as early as the 1970s and has been widely applied in the dynamic prediction and effective evaluation of oilfield development.Through extensive applications and studies...Tong's B-type water drive method was proposed as early as the 1970s and has been widely applied in the dynamic prediction and effective evaluation of oilfield development.Through extensive applications and studies,many researchers found that the statistical constants in the formula of the Tong's B-type water drive method(also referred to as the Tong's B-type formula)are not applicable to multiple types of reservoirs,especially low-permeability ones,due to the limited range of reservoir types when the formula was conceived.Moreover,they put forward suggestions to improve the Tong's B-type formula,most of which focused on the research and calculation of the first constant in the formula.For oilfields in the development stages of high or ultra-high water cuts,it is widely accepted that different types of reservoirs have different limit water cuts.This understanding naturally makes it necessary to further modify the Tong's B-type formula.It is practically significant to establish the water drive formula and cross plot considering that the two constants in the formula vary with reservoir type.By analyzing the derivation process and conditions of the Tong's B-type formula,this study points out two key problems,i.e.,the two constants 7.5 and 1.69 in the formula are not applicable to all types of reservoir.Given this,this study establishes a function between key reservoir parameters and the first constant and another function between key reservoir parameters and recovery efficiency.Based on the established two functions and considering that different types of oil reservoir have different limit water cuts,this study develops an improved Tong's B-type formula and prepares the corresponding improved cross plot.The results of this study will improve the applicability and accuracy of Tong's B-type water drive method in predicting the trend of water cut increasing for different types of oil reservoirs.展开更多
BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,h...BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)affects more than one-quarter of the global population.Due to the lack of approved chemical agents,many patients seek treatment from traditional Chinese medicine(TCM)f...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)affects more than one-quarter of the global population.Due to the lack of approved chemical agents,many patients seek treatment from traditional Chinese medicine(TCM)formulas.A variety of systematic reviews have been published regarding the effectiveness and safety of TCM formulas for NAFLD.AIM To critically appraise available systematic reviews and sort out the high-quality evidence on TCM formulas for the management of NAFLD.METHODS Seven databases were systematically searched from their inception to 28 February 2020.The search terms included“non-alcoholic fatty liver disease,”“Chinese medicines,”“systematic review,”and their synonyms.Systematic reviews involving TCM formulas alone or in combination with conventional medications were included.The methodological quality and risk of bias of eligible systematic reviews were evaluated by using A Measure Tool to Assess Systematic Reviews 2(AMSTAR 2)and Risk of Bias in Systematic Review(ROBIS).The quality of outcomes was assessed by the Grading of Recommendations Assessment,Development and Evaluation(GRADE)system.RESULTS Seven systematic reviews were ultimately included.All systematic reviews were conducted based on randomized controlled trials and published in the last decade.According to the AMSTAR 2 tool,one systematic review was judged as having a moderate confidence level,whereas the other studies were rated as having a low or extremely low level of confidence.The ROBIS tool showed that the included systematic reviews all had a high risk of bias due to insufficient consideration of identified concerns.According to the GRADE system,only two outcomes were determined as high quality;namely,TCM formulas with the HuoXueHuaYu principle were better than conventional medications in ultrasound improvement,and TCM formulas were superior to antioxidants in alanine aminotransferase normalization.Other outcomes were downgraded to lower levels,mainly because of heterogeneity among studies,not meeting optimal information sample size,and inclusion of excessive numbers of small sample studies.Nevertheless,the evidence quality of extracted outcomes should be further downgraded when applying to clinical practice due to indirectness.CONCLUSION The quality of available systematic reviews was not satisfactory.Researchers should avoid repeatedly conducting systematic reviews in this area and focus on designing rigorous randomized controlled trials to support TCM formula applications.展开更多
A test set-up called hyperbaric unmanned tester has been developed to assess the safety andreliability of deep sea respirator before manned testing. The tester possesses three basic capabili-ties: First, it is to simu...A test set-up called hyperbaric unmanned tester has been developed to assess the safety andreliability of deep sea respirator before manned testing. The tester possesses three basic capabili-ties: First, it is to simulate the operational conditions of underwater breathing apparatus. Thatis, it can reproduce ambient pressure as great as that of 300 meters deep sea water and ambienttemperature ranging between 4℃ and 40℃. It is also capable of reproducing the diver’s posture展开更多
Based on the research on the relevant background and significance of the sustainable development of agricultural cultural heritage,taking Wannian rice cultivation culture system as an example and its natural environme...Based on the research on the relevant background and significance of the sustainable development of agricultural cultural heritage,taking Wannian rice cultivation culture system as an example and its natural environment,traditional agricultural production activities,unique cultural patterns,socio-economic development and protection,and protection and development approach as the basis for evaluation,an evaluation index system for the sustainable development of Wannian rice cultivation culture system was constructed.Each index was quantified and standardized,and their weight was determined through the analytic hierarchy process to obtain the comprehensive evaluation value of the sustainable development of Wannian rice cultivation culture system.The evaluation value was analyzed to propose the main issues in the sustainable development of Wannian rice cultivation culture.展开更多
The role of human ether a-go-go related gene(hERG) in electrically excitable cells has long been known.hERG currents IKr contribute to the re-polarisation phase 3 of the cardiac action potential. Mutations of this cha...The role of human ether a-go-go related gene(hERG) in electrically excitable cells has long been known.hERG currents IKr contribute to the re-polarisation phase 3 of the cardiac action potential. Mutations of this channel causes long QT syndrome. N629D hERG mutation(GFGN to GFGD) alters the pore selectivity signature sequence.N629D was over-expressed, via adenoviral gene transfer,in car-diomyocytes derived from mouse embryonic stem cells,the "IKr" showed outward rectification and an inward tail current,while WT IKr showed inward rectification and a positive tail current.N629D "IKr" phenotype also altered resting membrane potential and caused arrhythmia.Since hERG was reported to express in early stage of cardiogenesis,the role of the ERG potassium channel in cardiac development was elaborated in an in vivo model of a homozygous. The hERG N629D mutation was introduced into the orthologous mouse gene,mERG,by homologous recombination in mouse embryonic stem cells. N629D/N629D homozygous mutation results in embryonic lethality(died by E11.5).The mutation displayed defect cardiac morphogenesis including altered looping architecture,poorly developed bulbus cordis,and distorted aortic sac and branchial arches. N629D/N629D myocytes from embryonic day 9.5 embryos manifested complete loss of IKr function, depolarized resting potential,prolonged action potential duration(LQT),failure to repolarize,and propensity to oscillatory arrhythmias.Because deletion of transcription factor Hand2 produces apoptosis in similar regions and with a similar final developmental phenotype,Hand2 expression was evaluated. Robust decrease in Hand2 expression was observed in the secondary heart field in N629D/N629D embryos. mERG protein expression in the developing embryonic heart is not homogeneous.The protein expression is exaggerated in the right ventricle and in the outflow tract.N629D/N629D embryos manifest extensive apoptosis particularly in the first branchial arch and the facial region.Given that cells from the branchial arch populate the outflow tract,the early apoptosis,in the branchial arch and facial region would prevent those cells from contributing to the development of the outflow tract in N629D/N629D hearts.The working model is that the Hand2 expres- sion is down regulated in N629D/N629D embryonic right ventricle and outflow tract because progenitor cells that populate the outflow tract undergo apoptosis while in the facial region and branchial arch. Thus tissues that would be expected to express Hand2 are absent,simply because those structures fail to develop.N629D/N629D embryos also displayed defects in both extraembryonic and intraem-bryonic vasculature.Yolk sac from N629D/N629D homozygous embryos revealed primary vascular networks formed,while they failed to remodel into more complex vascular structures,unlike wild-type yolk sacs at E9.5 N629D/N629D embryo yolk sacs at E9.5 display absence of visible vessels.Intraembry-onic vessels in the mutant showed less complex branching in comparison with the normal vessels structure in WT embryo,dorsal aorta exhibited abnormally formation and small lumens.Whole mount in situ hybridization displayed hERG was also expressed in E9.5 yolk sac and dorsal aorta.Immunofluorescence showed the co-localization of hERG and Cd31 and smooth muscle actin in E10.5. The role of hERG protein in the development of vasculature is further evaluated by using Cre-loxP-based mouse model for tissue specific hERG mutation expression.展开更多
文摘Based on the data of the construction industry in Henan Province, China, from 2005 to 2020, the high-quality development level of the construction industry in Henan Province is measured. Firstly, this paper constructs the indicator system based on the high-quality development theory and the characteristic of the construction industry from seven dimensions: industrial scale, industrial efficiency, industrial benefits, industrial innovation, industrial risk, industrial potential, and the green development of the construction industry. Secondly, using the global principal component analysis (PCA) method to measure the high-quality development level. Thirdly, cluster analysis is applied to measure the relative changes of various dimensions in different stages. The results show that overall the high-quality development level of the construction industry in Henan province is increasing, but different indicators perform differently in various stages, and the changes in real estate policies have a significant impact on this. Finally, based on these findings, we think it is better to reduce real estate dependence, promote the application of new materials and technologies and maintain the stability of real estate policies.
基金National Science and Technology Major Project(2017ZX05049)。
文摘This paper analyzes the differences in geological and development characteristics between continental shale oil in China and marine shale oil in North America, reviews the evaluation methods and technological progress of the continental shale oil development in China, and points out the existing problems and development directions of the continental shale oil development. The research progress of development evaluation technologies such as favorable lithofacies identification, reservoir characterization, mobility evaluation, fracability evaluation, productivity evaluation and geological-mathematical modeling integration are introduced. The efficient exploration and development of continental shale oil in China are faced with many problems, such as weak basic theoretical research, imperfect exploration and development technology system, big gap in engineering technology between China and other countries, and high development cost. Three key research issues must be studied in the future:(1) forming differentiated development technologies of continental shale oil through geological and engineering integrated research;(2) strengthening the application of big data and artificial intelligence to improve the accuracy of development evaluation;(3) tackling enhanced shale oil recovery technology and research effective development method, so as to improve the development effect and benefit.
文摘This study aimed to develop a guideline for therapeutic drug monitoring(TDM) of vancomycin. We adopted the new guideline definition from the Institute of Medicine(IOM), adhered closely to the six domains of the Appraisal of Guidelines for Research & Evaluation Ⅱ(AGREE Ⅱ), and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome(PICO) and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation(GRADE).
基金Phased Achievement of the Subside Project "Studies on Classification of Recreational Fishery Resources and Evaluation on its Development" of Chinese Marine Research and Development Center in2008(Grant no.AOCQN200816)
文摘Recreational fishery is the combination of traditional fishery and modern leisure activities.Development of recreational fishery resources must be based on related resources,but the present research on recreational fishery is mainly confined to the development of leisure projects,the definition of connotation and scope of recreational fishery resources is rather vague,and there is no precise classification and evaluation system.According to the resources attributes,resources functions,and tourism resources classification,investigation and evaluation standard,recreational fishery resources include a number of different types.Expert Scoring Method and Analytic Hierarchy Process can be used to determine the evaluation factors of recreational fishery resources and their weights,and then make comprehensive evaluation on recreational fishery resources of different regions and types,so as to improve the scientific nature of recreational fishery development.
文摘Rural revitalization strategy is an important strategic layout of rural development in the new era of the CPC Central Committee,and scientific and reasonable determination of village types is an important measure to promote rural revitalization by classification.The villages of Wan’an County were selected as the research object.Firstly,the factors that have a key impact on the development of the villages were extracted and qualitatively analyzed to preliminarily screen and judge their types.Secondly,the evaluation index system of development potential of the villages was constructed to quantitatively evaluate and reasonably classify the villages.Finally,the spatial distribution characteristics and quantity of different villages were revealed,and differentiated development strategies were proposed.
文摘Tong's B-type water drive method was proposed as early as the 1970s and has been widely applied in the dynamic prediction and effective evaluation of oilfield development.Through extensive applications and studies,many researchers found that the statistical constants in the formula of the Tong's B-type water drive method(also referred to as the Tong's B-type formula)are not applicable to multiple types of reservoirs,especially low-permeability ones,due to the limited range of reservoir types when the formula was conceived.Moreover,they put forward suggestions to improve the Tong's B-type formula,most of which focused on the research and calculation of the first constant in the formula.For oilfields in the development stages of high or ultra-high water cuts,it is widely accepted that different types of reservoirs have different limit water cuts.This understanding naturally makes it necessary to further modify the Tong's B-type formula.It is practically significant to establish the water drive formula and cross plot considering that the two constants in the formula vary with reservoir type.By analyzing the derivation process and conditions of the Tong's B-type formula,this study points out two key problems,i.e.,the two constants 7.5 and 1.69 in the formula are not applicable to all types of reservoir.Given this,this study establishes a function between key reservoir parameters and the first constant and another function between key reservoir parameters and recovery efficiency.Based on the established two functions and considering that different types of oil reservoir have different limit water cuts,this study develops an improved Tong's B-type formula and prepares the corresponding improved cross plot.The results of this study will improve the applicability and accuracy of Tong's B-type water drive method in predicting the trend of water cut increasing for different types of oil reservoirs.
文摘BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.
基金Evidence-based Capacity Building Project for Basic Traditional Chinese Medicine-Specialized Diseases,No.2019XZZX-XH012Shanghai Three-year Action Plan for Accelerating the Development of Traditional Chinese Medicine,No.ZY(2018-2020)-CCCX-2002-01.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)affects more than one-quarter of the global population.Due to the lack of approved chemical agents,many patients seek treatment from traditional Chinese medicine(TCM)formulas.A variety of systematic reviews have been published regarding the effectiveness and safety of TCM formulas for NAFLD.AIM To critically appraise available systematic reviews and sort out the high-quality evidence on TCM formulas for the management of NAFLD.METHODS Seven databases were systematically searched from their inception to 28 February 2020.The search terms included“non-alcoholic fatty liver disease,”“Chinese medicines,”“systematic review,”and their synonyms.Systematic reviews involving TCM formulas alone or in combination with conventional medications were included.The methodological quality and risk of bias of eligible systematic reviews were evaluated by using A Measure Tool to Assess Systematic Reviews 2(AMSTAR 2)and Risk of Bias in Systematic Review(ROBIS).The quality of outcomes was assessed by the Grading of Recommendations Assessment,Development and Evaluation(GRADE)system.RESULTS Seven systematic reviews were ultimately included.All systematic reviews were conducted based on randomized controlled trials and published in the last decade.According to the AMSTAR 2 tool,one systematic review was judged as having a moderate confidence level,whereas the other studies were rated as having a low or extremely low level of confidence.The ROBIS tool showed that the included systematic reviews all had a high risk of bias due to insufficient consideration of identified concerns.According to the GRADE system,only two outcomes were determined as high quality;namely,TCM formulas with the HuoXueHuaYu principle were better than conventional medications in ultrasound improvement,and TCM formulas were superior to antioxidants in alanine aminotransferase normalization.Other outcomes were downgraded to lower levels,mainly because of heterogeneity among studies,not meeting optimal information sample size,and inclusion of excessive numbers of small sample studies.Nevertheless,the evidence quality of extracted outcomes should be further downgraded when applying to clinical practice due to indirectness.CONCLUSION The quality of available systematic reviews was not satisfactory.Researchers should avoid repeatedly conducting systematic reviews in this area and focus on designing rigorous randomized controlled trials to support TCM formula applications.
文摘A test set-up called hyperbaric unmanned tester has been developed to assess the safety andreliability of deep sea respirator before manned testing. The tester possesses three basic capabili-ties: First, it is to simulate the operational conditions of underwater breathing apparatus. Thatis, it can reproduce ambient pressure as great as that of 300 meters deep sea water and ambienttemperature ranging between 4℃ and 40℃. It is also capable of reproducing the diver’s posture
基金Sponsored by Social Science Planning Project of Jiangxi Province(19YS06)Science and Technology Project of Education Department of Jiangxi Province(GJJ190196)+1 种基金Basic Education Research Project of Jiangxi Province(SZUNDZH2020-1138)Culture and Art Science Planning Project of Jiangxi Province(YG2021134)。
文摘Based on the research on the relevant background and significance of the sustainable development of agricultural cultural heritage,taking Wannian rice cultivation culture system as an example and its natural environment,traditional agricultural production activities,unique cultural patterns,socio-economic development and protection,and protection and development approach as the basis for evaluation,an evaluation index system for the sustainable development of Wannian rice cultivation culture system was constructed.Each index was quantified and standardized,and their weight was determined through the analytic hierarchy process to obtain the comprehensive evaluation value of the sustainable development of Wannian rice cultivation culture system.The evaluation value was analyzed to propose the main issues in the sustainable development of Wannian rice cultivation culture.
文摘The role of human ether a-go-go related gene(hERG) in electrically excitable cells has long been known.hERG currents IKr contribute to the re-polarisation phase 3 of the cardiac action potential. Mutations of this channel causes long QT syndrome. N629D hERG mutation(GFGN to GFGD) alters the pore selectivity signature sequence.N629D was over-expressed, via adenoviral gene transfer,in car-diomyocytes derived from mouse embryonic stem cells,the "IKr" showed outward rectification and an inward tail current,while WT IKr showed inward rectification and a positive tail current.N629D "IKr" phenotype also altered resting membrane potential and caused arrhythmia.Since hERG was reported to express in early stage of cardiogenesis,the role of the ERG potassium channel in cardiac development was elaborated in an in vivo model of a homozygous. The hERG N629D mutation was introduced into the orthologous mouse gene,mERG,by homologous recombination in mouse embryonic stem cells. N629D/N629D homozygous mutation results in embryonic lethality(died by E11.5).The mutation displayed defect cardiac morphogenesis including altered looping architecture,poorly developed bulbus cordis,and distorted aortic sac and branchial arches. N629D/N629D myocytes from embryonic day 9.5 embryos manifested complete loss of IKr function, depolarized resting potential,prolonged action potential duration(LQT),failure to repolarize,and propensity to oscillatory arrhythmias.Because deletion of transcription factor Hand2 produces apoptosis in similar regions and with a similar final developmental phenotype,Hand2 expression was evaluated. Robust decrease in Hand2 expression was observed in the secondary heart field in N629D/N629D embryos. mERG protein expression in the developing embryonic heart is not homogeneous.The protein expression is exaggerated in the right ventricle and in the outflow tract.N629D/N629D embryos manifest extensive apoptosis particularly in the first branchial arch and the facial region.Given that cells from the branchial arch populate the outflow tract,the early apoptosis,in the branchial arch and facial region would prevent those cells from contributing to the development of the outflow tract in N629D/N629D hearts.The working model is that the Hand2 expres- sion is down regulated in N629D/N629D embryonic right ventricle and outflow tract because progenitor cells that populate the outflow tract undergo apoptosis while in the facial region and branchial arch. Thus tissues that would be expected to express Hand2 are absent,simply because those structures fail to develop.N629D/N629D embryos also displayed defects in both extraembryonic and intraem-bryonic vasculature.Yolk sac from N629D/N629D homozygous embryos revealed primary vascular networks formed,while they failed to remodel into more complex vascular structures,unlike wild-type yolk sacs at E9.5 N629D/N629D embryo yolk sacs at E9.5 display absence of visible vessels.Intraembry-onic vessels in the mutant showed less complex branching in comparison with the normal vessels structure in WT embryo,dorsal aorta exhibited abnormally formation and small lumens.Whole mount in situ hybridization displayed hERG was also expressed in E9.5 yolk sac and dorsal aorta.Immunofluorescence showed the co-localization of hERG and Cd31 and smooth muscle actin in E10.5. The role of hERG protein in the development of vasculature is further evaluated by using Cre-loxP-based mouse model for tissue specific hERG mutation expression.