AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE ce...AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).展开更多
AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepi...AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.展开更多
AIM:To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor(VEGF)-A,VEGF-B,and placental growth factor(PLGF)levels after intravitreal inje...AIM:To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor(VEGF)-A,VEGF-B,and placental growth factor(PLGF)levels after intravitreal injections for the neovascular age-related macular degeneration(AMD).METHODS:Thir ty-five patients(35 eyes)with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol.Bestcorrected visual acuity(BCVA)and central retinal thickness(CRT)were detected before the intravitreal injection and at 1,3,and 12mo after conbercept treatment.The levels of serum VEGF-A,VEGF-B,and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments.RESULTS:At baseline,the mean BCVA score was 39.89±14.64 letters.The mean BCVA scores were 51.03±15.78,56.71±14.38,and 52.49±10.16 letters at 1,3,and 12mo after conbercept treatment,and the BCVA improvements were all significant,respectively(P<0.05).At baseline,the mean CRT was 436.7±141.9μm.At 1,3,and 12mo after conbercept treatment,the mean CRT values were 335.1±147.8,301.1±116.5,and 312.2±98.22μm,and the CRT improvements were all significant,respectively(P<0.05).At baseline,1 and 12mo after conbercept treatment,the mean levels of serum VEGF-A were 1013.8±454.3,953.1±426.4,and 981.5±471.7 pg/mL,the mean levels of serum VEGF-B were 46.93±24.76,42.99±19.16,and 45.32±18.76 pg/mL,the mean levels of serum PLGF at these points were 251.7±154.9,241.3±166.7,and 245.6±147.2 pg/mL,respectively.Compared with the baseline,the levels of serum VEGF-A,VEGF-B,and PLGF did not significantly change at 1 and 12mo after conbercept treatment,respectively(P>0.05).CONCLUSION:Conbercept intravitreal injection leads to BCVA and CRT improvement,however,it does not significantly affect systemic serum VEGF-A,VEGF-B,and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.展开更多
The demand for graphite resources has been increasing due to its extensive use.Graphite deposits in China are mainly distributed in Heilongjiang,Innner Mogolia,Sichuan,Shanxi and Shandong,characterized by "one ol...The demand for graphite resources has been increasing due to its extensive use.Graphite deposits in China are mainly distributed in Heilongjiang,Innner Mogolia,Sichuan,Shanxi and Shandong,characterized by "one old & one new" and "many in east & few in west".There are mainly three genetic types,including regional metamorphic type,contact metamorphic type and hydrothermal type.Here we provide a summary of the metallogenic regularity and 15 metallogenic belts in China based on the study of the geology of national graphite deposits.In recent years,great progress has been made in the research of genesis,mineral exploration and evaluation on graphite deposits,which indicate great potential for graphite resource in China.The authors suggest that the research on geochronology,ore sources,the genesis of crystalline graphite and exploration for hydrothermal graphite in China should be heightened.展开更多
Objective: To study the evaluation value of CTA for vertebrobasilar artery stenosis in patients with posterior circulation cerebral infarction and its correlation with serum biochemical indexes. Methods: A total of 14...Objective: To study the evaluation value of CTA for vertebrobasilar artery stenosis in patients with posterior circulation cerebral infarction and its correlation with serum biochemical indexes. Methods: A total of 148 patients who were treated in Maanshan Shiqiye Hospital between June 2014 and February 2017 due to vertebrobasilar artery stenosis were selected as the research subjects and divided into cerebral infarction group and transient ischemic attack (TIA) group according to the imageological examination. CTA was used to evaluate vertebrobasilar atherosclerotic plaque properties, and enzyme-linked immunosorbent assay kit was used to determine the levels of nerve injury markers, inflammatory response-related molecules and plaque property-related protease molecules. Results: The positive rate of posterior circulation plaque in cerebral infarction group was obviously higher than that in TIA group, and the positive rate of unstable plaque, fibrous plaque and calcified plaque were higher than those in TIA group;serum NSE, S100B, UCH-L1, GFAP, ICAM-1, VCAM-1, PECAM-1, VE-cadherin, YKL-40, CatS, MMP9, MMP10 and ADAMTS12 levels of cerebral infarction group of patients with unstable plaque, fibrous plaque and calcified plaque were all higher than those of TIA group;serum NSE, S100B, UCH-L1, GFAP, ICAM-1, VCAM-1, PECAM-1, VE-cadherin, YKL-40, CatS, MMP9, MMP10 and ADAMTS12 levels of cerebral infarction group of patients with unstable plaque and fibrous plaque were all higher than those of patients with calcified plaque, and serum NSE, S100B, UCH-L1, GFAP, ICAM-1, VCAM-1, PECAM-1, VE-cadherin, YKL-40, CatS, MMP9, MMP10 and ADAMTS12 levels of cerebral infarction group of patients with unstable plaque were all higher than those of patients with fibrous plaque. Conclusion: CTA can accurately assess the property of vertebrobasilar atherosclerotic plaque in patients with posterior circulation cerebral infarction and is closely related to the degree of nerve injury and the change of plaque property.展开更多
The North China Craton(NCC)experienced strong destruction(i.e.,decratonization)during the Mesozoic,which triggered intensive magmatism,tectonism and thermal events and formed large-scale gold and other metal deposits ...The North China Craton(NCC)experienced strong destruction(i.e.,decratonization)during the Mesozoic,which triggered intensive magmatism,tectonism and thermal events and formed large-scale gold and other metal deposits in the eastern part of the craton.However,how the decratonization controls the formation and distribution of large-scale of gold and other metal deposits is not very clear.Based on a large number of published data and new results,this paper systematically summarizes all the data for the rock assemblages,chronology,geochemistry and petrogenesis of Mesozoic magmatic rocks,as well as for the mineralizing ages of gold and other metal deposits and the evolution of the Mesozoic basins in the eastern NCC.The results are used to restore the extensional rates of Mesozoic to Cenozoic basins and the strike-slip distance of the Tanlu Fault,to ascertain the location of the Paleo-Pacific plate subduction zones during the Mesozoic to Cenozoic,and to reconstruct the temporal and spatial distribution of Mesozoic gold and other metal deposits and magmatic rocks in the eastern NCC.It is obtained that the magmatism and mineralization in the eastern NCC westward migrate from east to west during the Early to Middle Jurassic,but they eastward migrate from west to east during the Early Cretaceous.The metallogenesis of these deposits is genetically related to magmatism,and the magmas provided some ore-forming materials and fluids for the generation of metal deposits.The geodynamic mechanism of decratonization and related magmatism and mineralization is proposed,i.e.,the westward low-angle subduction of the Paleo-Pacific slab beneath the NCC formed continental magmatic arc with plenty of porphyry Cu-Mo-Au deposits in the Jurassic,similar to the Andean continental arc in South America.The mantle wedge was metasomatized by the fluids/melts derived from the subducting slab,laying a material foundation for hydrothermal mineralization in the Early Cretaceous.While the rollback of the subducting slab with gradually increasing subduction angle and the retreat of the subduction zones during the Early Cretaceous induced strong destruction of the craton and the formation of extensive magmatic rocks and large-scale gold and other metal deposits.展开更多
Abundant arc-type magmatic and metamorphic rocks exist on Earth today,which provide insights into the equilibrium state of the subduction process.However,magmatic samples generated during the initial stage of subducti...Abundant arc-type magmatic and metamorphic rocks exist on Earth today,which provide insights into the equilibrium state of the subduction process.However,magmatic samples generated during the initial stage of subduction is largely unknown.This hinders our understanding of the subduction initiation process and by inference,the onset of plate tectonics as well as the history of crustal formation.To address this issue,we carried out a comprehensive geochemical-geochronological study of a suite of Late Triassic to mid-Jurassic plutonic rocks from southern Alaska that potentially represent magmas from the initial to mature stages of arc formation.While all studied samples show typical arc-type geochemical signatures,i.e.,enrichment of large ion lithophile elements(LILEs)and depletion of high field strength elements(HFSEs)relative to the heavy rare earth elements(HREEs),the Late Triassic trondhjemites show unique geochemical features such as strongly positiveε_(Hf)(t)andε_(Nd)(t)coupled with lowerδ^(18)O(average 4.77‰±0.09‰).These signatures,along with its higher zircon saturation temperatures compared with younger plutonic rocks,are best explained by shallow partial melting of subducting high-temperature hydrothermally altered lower oceanic crust(i.e.,gabbro).If true,these surprising findings would open up new ways to study subduction initiation which would have important bearing on future research on the onset of global plate tectonics and the formation of the continental crust.展开更多
基金Supported by the Natural Science Foundation of Shaanxi Province,China(No.2022JM-521).
文摘AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).
基金the Natural Science Foundation of Shaanxi Province(No.2022JM-521)the Science and Technology Plan Project of Xi’an(No.21YXYJ0031).
文摘AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.
基金Supported by the Bethune Lumitin Research Funding for the young and middle-aged Ophthalmologists,China(No.BJ-LM202009)Shaanxi Province Key Research and Development Project,China(No.2022SF-312).
文摘AIM:To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor(VEGF)-A,VEGF-B,and placental growth factor(PLGF)levels after intravitreal injections for the neovascular age-related macular degeneration(AMD).METHODS:Thir ty-five patients(35 eyes)with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol.Bestcorrected visual acuity(BCVA)and central retinal thickness(CRT)were detected before the intravitreal injection and at 1,3,and 12mo after conbercept treatment.The levels of serum VEGF-A,VEGF-B,and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments.RESULTS:At baseline,the mean BCVA score was 39.89±14.64 letters.The mean BCVA scores were 51.03±15.78,56.71±14.38,and 52.49±10.16 letters at 1,3,and 12mo after conbercept treatment,and the BCVA improvements were all significant,respectively(P<0.05).At baseline,the mean CRT was 436.7±141.9μm.At 1,3,and 12mo after conbercept treatment,the mean CRT values were 335.1±147.8,301.1±116.5,and 312.2±98.22μm,and the CRT improvements were all significant,respectively(P<0.05).At baseline,1 and 12mo after conbercept treatment,the mean levels of serum VEGF-A were 1013.8±454.3,953.1±426.4,and 981.5±471.7 pg/mL,the mean levels of serum VEGF-B were 46.93±24.76,42.99±19.16,and 45.32±18.76 pg/mL,the mean levels of serum PLGF at these points were 251.7±154.9,241.3±166.7,and 245.6±147.2 pg/mL,respectively.Compared with the baseline,the levels of serum VEGF-A,VEGF-B,and PLGF did not significantly change at 1 and 12mo after conbercept treatment,respectively(P>0.05).CONCLUSION:Conbercept intravitreal injection leads to BCVA and CRT improvement,however,it does not significantly affect systemic serum VEGF-A,VEGF-B,and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.
文摘The demand for graphite resources has been increasing due to its extensive use.Graphite deposits in China are mainly distributed in Heilongjiang,Innner Mogolia,Sichuan,Shanxi and Shandong,characterized by "one old & one new" and "many in east & few in west".There are mainly three genetic types,including regional metamorphic type,contact metamorphic type and hydrothermal type.Here we provide a summary of the metallogenic regularity and 15 metallogenic belts in China based on the study of the geology of national graphite deposits.In recent years,great progress has been made in the research of genesis,mineral exploration and evaluation on graphite deposits,which indicate great potential for graphite resource in China.The authors suggest that the research on geochronology,ore sources,the genesis of crystalline graphite and exploration for hydrothermal graphite in China should be heightened.
基金Natural Science Foundation of Anhui Province No:1308085MH158.
文摘Objective: To study the evaluation value of CTA for vertebrobasilar artery stenosis in patients with posterior circulation cerebral infarction and its correlation with serum biochemical indexes. Methods: A total of 148 patients who were treated in Maanshan Shiqiye Hospital between June 2014 and February 2017 due to vertebrobasilar artery stenosis were selected as the research subjects and divided into cerebral infarction group and transient ischemic attack (TIA) group according to the imageological examination. CTA was used to evaluate vertebrobasilar atherosclerotic plaque properties, and enzyme-linked immunosorbent assay kit was used to determine the levels of nerve injury markers, inflammatory response-related molecules and plaque property-related protease molecules. Results: The positive rate of posterior circulation plaque in cerebral infarction group was obviously higher than that in TIA group, and the positive rate of unstable plaque, fibrous plaque and calcified plaque were higher than those in TIA group;serum NSE, S100B, UCH-L1, GFAP, ICAM-1, VCAM-1, PECAM-1, VE-cadherin, YKL-40, CatS, MMP9, MMP10 and ADAMTS12 levels of cerebral infarction group of patients with unstable plaque, fibrous plaque and calcified plaque were all higher than those of TIA group;serum NSE, S100B, UCH-L1, GFAP, ICAM-1, VCAM-1, PECAM-1, VE-cadherin, YKL-40, CatS, MMP9, MMP10 and ADAMTS12 levels of cerebral infarction group of patients with unstable plaque and fibrous plaque were all higher than those of patients with calcified plaque, and serum NSE, S100B, UCH-L1, GFAP, ICAM-1, VCAM-1, PECAM-1, VE-cadherin, YKL-40, CatS, MMP9, MMP10 and ADAMTS12 levels of cerebral infarction group of patients with unstable plaque were all higher than those of patients with fibrous plaque. Conclusion: CTA can accurately assess the property of vertebrobasilar atherosclerotic plaque in patients with posterior circulation cerebral infarction and is closely related to the degree of nerve injury and the change of plaque property.
基金project“Deep Process and Mechanism of Metallogenic System in the North China Craton”supported by the National Key R&D Program of China(Grant No.2016YFC0600109)the National Natural Science Foundation of China(Grant No.41688103)。
文摘The North China Craton(NCC)experienced strong destruction(i.e.,decratonization)during the Mesozoic,which triggered intensive magmatism,tectonism and thermal events and formed large-scale gold and other metal deposits in the eastern part of the craton.However,how the decratonization controls the formation and distribution of large-scale of gold and other metal deposits is not very clear.Based on a large number of published data and new results,this paper systematically summarizes all the data for the rock assemblages,chronology,geochemistry and petrogenesis of Mesozoic magmatic rocks,as well as for the mineralizing ages of gold and other metal deposits and the evolution of the Mesozoic basins in the eastern NCC.The results are used to restore the extensional rates of Mesozoic to Cenozoic basins and the strike-slip distance of the Tanlu Fault,to ascertain the location of the Paleo-Pacific plate subduction zones during the Mesozoic to Cenozoic,and to reconstruct the temporal and spatial distribution of Mesozoic gold and other metal deposits and magmatic rocks in the eastern NCC.It is obtained that the magmatism and mineralization in the eastern NCC westward migrate from east to west during the Early to Middle Jurassic,but they eastward migrate from west to east during the Early Cretaceous.The metallogenesis of these deposits is genetically related to magmatism,and the magmas provided some ore-forming materials and fluids for the generation of metal deposits.The geodynamic mechanism of decratonization and related magmatism and mineralization is proposed,i.e.,the westward low-angle subduction of the Paleo-Pacific slab beneath the NCC formed continental magmatic arc with plenty of porphyry Cu-Mo-Au deposits in the Jurassic,similar to the Andean continental arc in South America.The mantle wedge was metasomatized by the fluids/melts derived from the subducting slab,laying a material foundation for hydrothermal mineralization in the Early Cretaceous.While the rollback of the subducting slab with gradually increasing subduction angle and the retreat of the subduction zones during the Early Cretaceous induced strong destruction of the craton and the formation of extensive magmatic rocks and large-scale gold and other metal deposits.
基金This work was supported by the National Natural Science Foundation of China(41688103)the Ministry of Science and Technology of China(2016YFC0600109).
文摘Abundant arc-type magmatic and metamorphic rocks exist on Earth today,which provide insights into the equilibrium state of the subduction process.However,magmatic samples generated during the initial stage of subduction is largely unknown.This hinders our understanding of the subduction initiation process and by inference,the onset of plate tectonics as well as the history of crustal formation.To address this issue,we carried out a comprehensive geochemical-geochronological study of a suite of Late Triassic to mid-Jurassic plutonic rocks from southern Alaska that potentially represent magmas from the initial to mature stages of arc formation.While all studied samples show typical arc-type geochemical signatures,i.e.,enrichment of large ion lithophile elements(LILEs)and depletion of high field strength elements(HFSEs)relative to the heavy rare earth elements(HREEs),the Late Triassic trondhjemites show unique geochemical features such as strongly positiveε_(Hf)(t)andε_(Nd)(t)coupled with lowerδ^(18)O(average 4.77‰±0.09‰).These signatures,along with its higher zircon saturation temperatures compared with younger plutonic rocks,are best explained by shallow partial melting of subducting high-temperature hydrothermally altered lower oceanic crust(i.e.,gabbro).If true,these surprising findings would open up new ways to study subduction initiation which would have important bearing on future research on the onset of global plate tectonics and the formation of the continental crust.
