β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 （A〉G） mutations is one of the three most common mutations in China and Southeast Asia patients with β-th...β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 （A〉G） mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor （BE） system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 （A〉G） mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 （A〉G） homozygous mutation. Data showed that base editor could precisely correct HBB -28 （A〉G） mutation in the patient＇s primary cells. To model homozygous mutation disease embryos, we consb＇ucted nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured （IVM） oocytes.Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.展开更多
AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.M...AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.展开更多
Irritable bowel syndrome (IBS) is a functional intestinal disease characterized by abdominal pain or discomfort and altered bowel habits. It has drawn great attention because of its high prevalence, reoccurring sympto...Irritable bowel syndrome (IBS) is a functional intestinal disease characterized by abdominal pain or discomfort and altered bowel habits. It has drawn great attention because of its high prevalence, reoccurring symptoms, and severe influence on patients’ lives. Many clinical studies have demonstrated the efficacy of acupuncture-moxibustion in treating IBS. Increasing attention has been paid to research regarding the action mechanisms of acupuncture-moxibustion for IBS, and the adoption of modern techniques has achieved some progress. This article reviews the latest advances among action mechanism studies from the perspectives of gastrointestinal motility, visceral hypersensitivity, the brain-gut axis, the neuroendocrine system, and the immune system. It is shown that acupuncture-moxibustion can effectively regulate the above items, and thus, this treatment should have a high efficacy in the treatment of IBS. This article also identifies existing problems in current mechanism research and raises several ideas for future studies. Further revelations regarding these action mechanisms will promote the application of acupuncture-moxibustion in treating IBS.展开更多
With rapid economic growth and urbanization, the Yangtze River Delta(YRD) region in China has experienced serious air pollution challenges. In this study, we analyzed the air pollution characteristics and their relati...With rapid economic growth and urbanization, the Yangtze River Delta(YRD) region in China has experienced serious air pollution challenges. In this study, we analyzed the air pollution characteristics and their relationship with emissions and meteorology in the YRD region during 2014–2016. In recent years, the concentrations of all air pollutants, except O3,decreased. Spatially, the PM2.5, PM10, SO2, and CO concentrations were higher in the northern YRD region, and NO2 and O3 were higher in the central YRD region. Based on the number of non-attainment days(i.e., days with air quality index greater than 100), PM2.5 was the largest contributor to air pollution in the YRD region, followed by O3, PM10, and NO2.However, particulate matter pollution has declined gradually, while O3 pollution worsened.Meteorological conditions mainly influenced day-to-day variations in pollutant concentrations. PM2.5 concentration was inversely related to wind speed, while O3 concentration was positively correlated with temperature and negatively correlated with relative humidity.The air quality improvement in recent years was mainly attributed to emission reductions.During 2014–2016, PM2.5, PM10, SO2, NOx, CO, NH3, and volatile organic compound(VOC)emissions in the YRD region were reduced by 26.3%, 29.2%, 32.4%, 8.1%, 15.9%, 4.5%, and0.3%, respectively. Regional transport also contributed to the air pollution. During regional haze periods, pollutants from North China and East China aggravated the pollution in the YRD region. Our findings suggest that emission reduction and regional joint prevention and control helped to improve the air quality in the YRD region.展开更多
Heterotrimeric G proteins are known to function as messengers in numerous signal transduction pathways.The nullmutation of RGA(rice heterotrimeric G protein α subunit),which encodes the α subunit of heterotrimeric G...Heterotrimeric G proteins are known to function as messengers in numerous signal transduction pathways.The nullmutation of RGA(rice heterotrimeric G protein α subunit),which encodes the α subunit of heterotrimeric G proteinin rice,causes severe dwarfism and reduced responsiveness to gibberellic acid in rice.However,less is known aboutheterotrimeric G protein in brassinosteroid(BR)signaling,one of the well-understood phytohormone pathways.In thepresent study,we used root elongation inhibition assay,lamina inclination assay and coleoptile elongation analysis todemonstrated reduced sensitivity of dl mutant plants(caused by the null mutation of RGA)to 24-epibrassinolide(24-epiBL),which belongs to brassinosteroids and plays a wide variety of roles in plant growth and development.Moreover,RGA transcript level was decreased in 24-epiBL-treated seedlings in a dose-dependent manner.Our results show thatRGA is involved in rice brassinosteroid response,which may be beneficial to elucidate the molecular mechanisms of Gprotein signaling and provide a novel perspective to understand BR signaling in higher plants.展开更多
Background: Augmented reality(AR) technology is used to reconstruct three-dimensional(3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the v...Background: Augmented reality(AR) technology is used to reconstruct three-dimensional(3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes.Data Sources: The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were used for searching publications in the Pub Med database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles.Results: In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery,which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology.Conclusions: With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling,and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.展开更多
目的:评估阴性症状评估量表4条目(4-item Negative Symptom Assessment,NSA-4)中文版在精神分裂症患者中的信效度。方法:纳入172例精神分裂症患者进行NSA-4中文版及阴性症状评定量表(Scale for Assessment of Negative Symptoms,SANS)、...目的:评估阴性症状评估量表4条目(4-item Negative Symptom Assessment,NSA-4)中文版在精神分裂症患者中的信效度。方法:纳入172例精神分裂症患者进行NSA-4中文版及阴性症状评定量表(Scale for Assessment of Negative Symptoms,SANS)、PANSS、卡尔加里精神分裂症抑郁量表(Calgary Depression Scale for Schizophrenia,CDSS)评估。采用Cronbachα系数评价NSA-4中文版的内部一致性,采用组内相关系数(intraclass correlation coefficients,ICC)评价评分者间一致性,以Spearman相关分析评价重测信度。采用Spearman相关分析,以NSA-4中文版与SANS的相关性评价其效标效度,与PANSS、CDSS的相关性评价其聚合效度和区分效度。结果:NSA-4中文版的Cronbachα系数为0.788,ICC为0.661~0.958,重测信度r=0.860。NSA-4中文版与SANS的相关系数为r=0.801,与PANSS总分、PANSS阴性症状分及总体阴性症状评定的相关系数为r=0.528~0.834,与PANSS阳性症状分、一般病理分、CDSS总分相关系数为r=0.069~0.358。结论:NSA-4中文版具有良好的信效度,适用于精神分裂症患者阴性症状的临床快速评定。展开更多
基金We are grateful to Dr. Qi Zhou for helpful suggestions. This work was supported by National Key R＆D Program of China （2017YFC1001901 and 2017YFC1001600）, the Science and Technology Planning Project of Guangdong Province （2015B020228002）, the Guangzhou Science and Technology Project （201707010085） and the National Natural Science Foundation of China （Grant No. 81771579）.
文摘β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 （A〉G） mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor （BE） system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 （A〉G） mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 （A〉G） homozygous mutation. Data showed that base editor could precisely correct HBB -28 （A〉G） mutation in the patient＇s primary cells. To model homozygous mutation disease embryos, we consb＇ucted nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured （IVM） oocytes.Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
基金Supported by National Natural Science Foundation of ChinaNo.81460114+5 种基金Natural Science Foundation of Guangxi Zhuang Autonomous RegionNo.1355005-3-2 and No.2012GXNSFAA053143Chinese Traditional Medicine Science Foundation of Guangxi Zhuang Autonomous RegionNo.GZPT1238Science Foundation of Guangxi Department of EducationNo.201203YB036 and No.2013LX031
文摘AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.
基金Supported by National Natural Science Foundation of China,No.81273843,No.81072879National Key Basic Research Program of China,No.2009CB522900
文摘Irritable bowel syndrome (IBS) is a functional intestinal disease characterized by abdominal pain or discomfort and altered bowel habits. It has drawn great attention because of its high prevalence, reoccurring symptoms, and severe influence on patients’ lives. Many clinical studies have demonstrated the efficacy of acupuncture-moxibustion in treating IBS. Increasing attention has been paid to research regarding the action mechanisms of acupuncture-moxibustion for IBS, and the adoption of modern techniques has achieved some progress. This article reviews the latest advances among action mechanism studies from the perspectives of gastrointestinal motility, visceral hypersensitivity, the brain-gut axis, the neuroendocrine system, and the immune system. It is shown that acupuncture-moxibustion can effectively regulate the above items, and thus, this treatment should have a high efficacy in the treatment of IBS. This article also identifies existing problems in current mechanism research and raises several ideas for future studies. Further revelations regarding these action mechanisms will promote the application of acupuncture-moxibustion in treating IBS.
基金supported by the National Science and Technology Program of China(Nos.2017YFC0211601,2016YFC0202700)the National Natural Science Foundation of China(No.81571130090)the National Research Program for Key Issues in Air Pollution Control(No.DQGG0103)
文摘With rapid economic growth and urbanization, the Yangtze River Delta(YRD) region in China has experienced serious air pollution challenges. In this study, we analyzed the air pollution characteristics and their relationship with emissions and meteorology in the YRD region during 2014–2016. In recent years, the concentrations of all air pollutants, except O3,decreased. Spatially, the PM2.5, PM10, SO2, and CO concentrations were higher in the northern YRD region, and NO2 and O3 were higher in the central YRD region. Based on the number of non-attainment days(i.e., days with air quality index greater than 100), PM2.5 was the largest contributor to air pollution in the YRD region, followed by O3, PM10, and NO2.However, particulate matter pollution has declined gradually, while O3 pollution worsened.Meteorological conditions mainly influenced day-to-day variations in pollutant concentrations. PM2.5 concentration was inversely related to wind speed, while O3 concentration was positively correlated with temperature and negatively correlated with relative humidity.The air quality improvement in recent years was mainly attributed to emission reductions.During 2014–2016, PM2.5, PM10, SO2, NOx, CO, NH3, and volatile organic compound(VOC)emissions in the YRD region were reduced by 26.3%, 29.2%, 32.4%, 8.1%, 15.9%, 4.5%, and0.3%, respectively. Regional transport also contributed to the air pollution. During regional haze periods, pollutants from North China and East China aggravated the pollution in the YRD region. Our findings suggest that emission reduction and regional joint prevention and control helped to improve the air quality in the YRD region.
基金This project was supported by the Major State Basic Research Program of China （2005CB 120806）, National Natural Science Foundation of China for Distinguished Young Scholars （30525026） and the State Transgenic Plant Project （JY04-A-01）
文摘Heterotrimeric G proteins are known to function as messengers in numerous signal transduction pathways.The nullmutation of RGA(rice heterotrimeric G protein α subunit),which encodes the α subunit of heterotrimeric G proteinin rice,causes severe dwarfism and reduced responsiveness to gibberellic acid in rice.However,less is known aboutheterotrimeric G protein in brassinosteroid(BR)signaling,one of the well-understood phytohormone pathways.In thepresent study,we used root elongation inhibition assay,lamina inclination assay and coleoptile elongation analysis todemonstrated reduced sensitivity of dl mutant plants(caused by the null mutation of RGA)to 24-epibrassinolide(24-epiBL),which belongs to brassinosteroids and plays a wide variety of roles in plant growth and development.Moreover,RGA transcript level was decreased in 24-epiBL-treated seedlings in a dose-dependent manner.Our results show thatRGA is involved in rice brassinosteroid response,which may be beneficial to elucidate the molecular mechanisms of Gprotein signaling and provide a novel perspective to understand BR signaling in higher plants.
基金supported by grants from the Mission Plan Program of Beijing Municipal Administration of Hospitals(SML20152201)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding(ZYLX201712)+1 种基金the National Natural Science Foundation of China(81427803)Beijing Tsinghua Changgung Hospital Fund(12015C1039)
文摘Background: Augmented reality(AR) technology is used to reconstruct three-dimensional(3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes.Data Sources: The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were used for searching publications in the Pub Med database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles.Results: In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery,which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology.Conclusions: With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling,and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.
文摘目的:评估阴性症状评估量表4条目(4-item Negative Symptom Assessment,NSA-4)中文版在精神分裂症患者中的信效度。方法:纳入172例精神分裂症患者进行NSA-4中文版及阴性症状评定量表(Scale for Assessment of Negative Symptoms,SANS)、PANSS、卡尔加里精神分裂症抑郁量表(Calgary Depression Scale for Schizophrenia,CDSS)评估。采用Cronbachα系数评价NSA-4中文版的内部一致性,采用组内相关系数(intraclass correlation coefficients,ICC)评价评分者间一致性,以Spearman相关分析评价重测信度。采用Spearman相关分析,以NSA-4中文版与SANS的相关性评价其效标效度,与PANSS、CDSS的相关性评价其聚合效度和区分效度。结果:NSA-4中文版的Cronbachα系数为0.788,ICC为0.661~0.958,重测信度r=0.860。NSA-4中文版与SANS的相关系数为r=0.801,与PANSS总分、PANSS阴性症状分及总体阴性症状评定的相关系数为r=0.528~0.834,与PANSS阳性症状分、一般病理分、CDSS总分相关系数为r=0.069~0.358。结论:NSA-4中文版具有良好的信效度,适用于精神分裂症患者阴性症状的临床快速评定。
