AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was ev...AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo L.RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earliest(6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES.CONCLUSION Ada treatment, upon multidisciplinary(gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQo L in patients affected by ES.展开更多
The North China Craton (NCC) is a classical example of ancient destroyed cratons.Since the initiation of the North China Craton Destruction Project by the National Natural Science Foundation of China,numerous studies ...The North China Craton (NCC) is a classical example of ancient destroyed cratons.Since the initiation of the North China Craton Destruction Project by the National Natural Science Foundation of China,numerous studies have been conducted on the timing,scale,and mechanism of this destruction through combined interdisciplinary research.Available data suggest that the destruction occurred mainly in the eastern NCC,whereas the western NCC was only locally modified.The sedimentation,magmatic activities and structural deformation after cratonization at ～1.8 Ga indicate that the NCC destruction took place in the Mesozoic with a peak age of ca 125 Ma.A global comparison suggests that most cratons on Earth are not destroyed,although they have commonly experienced lithospheric thinning;destruction is likely to occur only when the craton has been disturbed by oceanic subduction.The destruction of the NCC was coincident with globally active plate tectonics and high mantle temperatures during the Cretaceous.The subducted Pacific slab destabilized mantle convection beneath the eastern NCC,which resulted in cratonic destruction in the eastern NCC.Delamination and/or thermal-mechanical-chemical erosion resulted from the destabilization of mantle convection.展开更多
Sphingosine-1-phosphate（S1P） is a bioactive lipid messenger in the cells that regulate gene expression and NF-κB signal pathway through unknown mechanisms.Recently,Cheng Luo,associate professor of DDDC in Shanghai ...Sphingosine-1-phosphate（S1P） is a bioactive lipid messenger in the cells that regulate gene expression and NF-κB signal pathway through unknown mechanisms.Recently,Cheng Luo,associate professor of DDDC in Shanghai Institute of Materia Medica,whose project was funded by the National Natural Science Foundation of China,joined in a research team led by Professor Sarah Spiegel of Virginia Commonwealth University.The team continuously made significant breakthroughs in understanding the regulation mechanism of Sphingosine-1- Phosphate.In September 2009,in a paper published on SCIENCE magazine（Science 2009, 325：1254-7）,they firstly demonstrated that S1P is a physiologically important regulator of histone deacetylases（HDACs）,HDACs are direct intracellular targets of S1P.Furthermore,they identified the mechanism that S1P regulates gene expression through regulating the activity of HDACs.In June 24th,2010,in another paper to be published on NATURE magazine（Nature 2010,June 24th,advance online publication,（doi：10.1038/ nature09128）） which reports the regulation of NF-κB signaling pathway by S1P.They demonstrate that S1P is the missing cofactor for TRAF2（tumour-necrosis factor receptor-associated factor 2） and indicate a new paradigm for the regulation of lysine-63- linked poly-ubiquitination.The study also highlight the key role of SphK1 and its product S1P in TNF-αsignalling and the canonical NF-κB activation pathway, and then play crucial role in inflammatory,antiapoptotic and immune processes.The identification of new mechanisms fay which S1P regulates gene expression and TNF and NF-κB signaling pathway will light up the road to develop novel inhibitors that might be useful for treatment of cancer and in- flammatory diseases.展开更多
文摘AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo L.RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earliest(6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES.CONCLUSION Ada treatment, upon multidisciplinary(gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQo L in patients affected by ES.
基金supported by the National Natural Science Foundation of China (Grant Nos. 90814000,90814002)
文摘The North China Craton (NCC) is a classical example of ancient destroyed cratons.Since the initiation of the North China Craton Destruction Project by the National Natural Science Foundation of China,numerous studies have been conducted on the timing,scale,and mechanism of this destruction through combined interdisciplinary research.Available data suggest that the destruction occurred mainly in the eastern NCC,whereas the western NCC was only locally modified.The sedimentation,magmatic activities and structural deformation after cratonization at ～1.8 Ga indicate that the NCC destruction took place in the Mesozoic with a peak age of ca 125 Ma.A global comparison suggests that most cratons on Earth are not destroyed,although they have commonly experienced lithospheric thinning;destruction is likely to occur only when the craton has been disturbed by oceanic subduction.The destruction of the NCC was coincident with globally active plate tectonics and high mantle temperatures during the Cretaceous.The subducted Pacific slab destabilized mantle convection beneath the eastern NCC,which resulted in cratonic destruction in the eastern NCC.Delamination and/or thermal-mechanical-chemical erosion resulted from the destabilization of mantle convection.
基金supported by Natural Science Foundation of China(Grant No.20972174)
文摘Sphingosine-1-phosphate（S1P） is a bioactive lipid messenger in the cells that regulate gene expression and NF-κB signal pathway through unknown mechanisms.Recently,Cheng Luo,associate professor of DDDC in Shanghai Institute of Materia Medica,whose project was funded by the National Natural Science Foundation of China,joined in a research team led by Professor Sarah Spiegel of Virginia Commonwealth University.The team continuously made significant breakthroughs in understanding the regulation mechanism of Sphingosine-1- Phosphate.In September 2009,in a paper published on SCIENCE magazine（Science 2009, 325：1254-7）,they firstly demonstrated that S1P is a physiologically important regulator of histone deacetylases（HDACs）,HDACs are direct intracellular targets of S1P.Furthermore,they identified the mechanism that S1P regulates gene expression through regulating the activity of HDACs.In June 24th,2010,in another paper to be published on NATURE magazine（Nature 2010,June 24th,advance online publication,（doi：10.1038/ nature09128）） which reports the regulation of NF-κB signaling pathway by S1P.They demonstrate that S1P is the missing cofactor for TRAF2（tumour-necrosis factor receptor-associated factor 2） and indicate a new paradigm for the regulation of lysine-63- linked poly-ubiquitination.The study also highlight the key role of SphK1 and its product S1P in TNF-αsignalling and the canonical NF-κB activation pathway, and then play crucial role in inflammatory,antiapoptotic and immune processes.The identification of new mechanisms fay which S1P regulates gene expression and TNF and NF-κB signaling pathway will light up the road to develop novel inhibitors that might be useful for treatment of cancer and in- flammatory diseases.
