DI-3n-butylphthalide is the active component isolated from the seeds of Apium graveolens Linn. A number of pharmacological and clinical studies have proven that dl-3n-butylphthalide is highly potent and multi-targeted...DI-3n-butylphthalide is the active component isolated from the seeds of Apium graveolens Linn. A number of pharmacological and clinical studies have proven that dl-3n-butylphthalide is highly potent and multi-targeted with low toxicity and has a long time-window for the treatment of ischemic cerebrovascular disease. The mechanisms underlying dl-3n-butylphthalide include improving mitochondrial function and microcirculation, inhibiting apoptosis and reducing oxidative stress. Furthermore, dl-3n-butylphthalide may also be promising for the treatment of neurodegenerative diseases, such as Alzheimer＇s disease, vascular dementia and Parkinson＇s disease.展开更多
The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistan...The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA ＋ AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Hart population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.展开更多
BACKGROUND： Some researches suggest that induced cyclooxygenase-2 （COX-2） can cause brain injury through a series of ways at the phase of cerebral ischemia/hypoxia. Plasminogen activator inhibitor type-1 （PAl-1） ...BACKGROUND： Some researches suggest that induced cyclooxygenase-2 （COX-2） can cause brain injury through a series of ways at the phase of cerebral ischemia/hypoxia. Plasminogen activator inhibitor type-1 （PAl-1） is a kind of inhibitor of serine stretch protein enzyme and is able to protect cell surface and microvascular basement membrane from degradation of protease and also protect contact surface among cells so as to maintain intecjrality of tissue structure. However, correlation of protective effect of flunar z ne on bran w th COX-2 and PAl-1 should be studied further. OBJECTTVE ： To observe the effect of flunarizine on expressions of COX-2 and PAl-1 protein in forebrain and degree of brain injury among gerbils after cerebral ischemia. DESIGN ： A randomized controlled animal study SETTING： Department of Neurology, the Second Xiangya Hospital of Central South University; Department of Neurology, Mawangdui Hospital of Hunan Province. MATERIALS： A total of 40 healthy gerbils, of both genders, aged 9 months, weighing （90±10） g, were selected in this study. Anti-COX-2 multi-antibody, anti-PAl-1 multi-antibody, SABC immunohistochemical kit and DAB kit were provided by Wuhan Boster Biological Engineering Co., Ltd.; and flunarizine capsule was provided by Xi＇an Yangsen Pharmaceutical Company （batch number： 041018726, dosage： 5 mg/pill）. METHODS： The experiment was carded out in Laboratory of Mental Disease, Hunan Provincial Geriatrics Institute affiliated by Hunan Provincial Mawangdui Hospital from January 2004 to March 2005. （1） All gerbils were randomly divided into cerebral ischemia group, flunarizine intervention group, sham operation group and norma control group with 10 in each group. Gerbils in normal control group were only cut off their heads. Gerbils in sham operation group were only dissected their bilateral common carotid arteries and sacrificed 1 day later. Gerbils in cerebral ischemia group and flunarizine intervention group were anesthetized, centrally cut open skin of neck, bluntly dissected bilateral common carotid arteries, clipped bilateral common carotid arteries with microvascular clamp for 10 minutes, then reperfused and sacrificed 3 in each group on the 1^st-, 3^rd- and 7^th-day reperfusion. One day before experiment, gerbils in flunarizine intervention group were given 20 mg/kg mixed flunarizine solution. （2） All gerbils were sacrificed in different periods. In addition, forebrain was fixed with 100 g/L formaldehyde, routinely embedded with paraffin, and cut into serial sections with the thickness of 5 μm. Neighboring brain tissues were done with routine HE staining and pathological changes were observed under optic microscope to evaluate the degree of brain injury. Expressions of COX-2 and PAl-1 protein in forebrain were detected with immunohistochemical technique, i.e., numbers of immune positive cells were accounted. （3）Averages of samples were compared with SNK-q test. MAIN OUTCOME MEASURES： Pathological changes of forebrain tissue and expressions of COX-2 and PAl-1 protein in forebrain of gerbils. RESULTS ： All 40 gerbils were involved in the final analysis. （1） Pathological changes of forebrain tissue： Morphologicel structure of cortex tissue was normal in normal control group and sham operation group. At 1 day after ischemia/reperfusion, nerve cells in cortex and hippocampus of forebrain were focal necrosis in cerebra ischemia group, and proliferation of glial cell was slight. In addition, at 3 days after ischemia/reperfusion nerve cells were sheet-like necrosis and proliferation of glial cell was obvious. Meanwhile, at 7 days after is chemia/reperfusion, nerve cells were necrosis in a large area and a lot of glial cells were proliferated. De grees of brain injury were severer in cerebral ischemia group than those in flunarizine intervention group at various time points. （2） Expressions of COX-2 and PAI-1 protein in forebrain： Numbers of COX-2 positive cells in flunarizine intervention group were 62.38±3.38, 33.84±2.48 and 13.82±2.23 at 1, 3 and 7 days after ischemia/reperfusion, respectively, which were less than those in cerebral ischemia group （73.08±2.11, 51.76± 2.38, 23.96±2.86; P〈 0.01）. Numbers of COX-2 positive cells in these two groups were decreased with the lasting time of ischemia/repeffusion. Expressions of PAI-1 in flunarizine intervention group were 14.48±2.0 ,27.44±3.06 and 41.84±2.48 at 1, 3 and 7 days after ischemia/reperfusion, respectively, which were highe than those in cerebral ischemia group （8.48±1.53, 20.93±2.16, 31.12±2.89; P 〈 0.01 ）. Expressions of PAl-1 protein in these two groups were increased with the lasting time of ischemialreperfusion.CONCLUSION ： Ischemia/reperfusion can increase the expressions of COX-2 and PAI-1 protein in forebrain of gerbils; however, pretreatment of flunarizine can down-regulate the expression of COX-2 but up-regulate the expression of PAI-1 protein so as to prevent brain injury after ischemia/reperfusion. Moreover, the preventive effect is time-dependent.展开更多
Pyroptosis is a type of programed cell death that differs from apoptosis,ferroptosis,or necrosis.Numerous studies have reported that it plays a critical role in tumorigenesis and modification of the tumor microenviron...Pyroptosis is a type of programed cell death that differs from apoptosis,ferroptosis,or necrosis.Numerous studies have reported that it plays a critical role in tumorigenesis and modification of the tumor microenvironment in multiple tumors.In this review,we briefly describe the canonical,non-canonical,and alternative mechanisms of pyroptotic cell death.We also summarize the potential roles of pyroptosis in oncogenesis,tumor development,and lung cancer treatment,including chemotherapy,radiotherapy,targeted therapy,and immunotherapy.Pyrop-tosis has double-edged effects on the modulation of the tumor environment and lung cancer treatment.Further exploration of pyroptosis-based drugs could provide novel therapeutic strategies for lung cancer.展开更多
The fluid flow of unconsolidated sandstone reservoir can be affected by compaction and sand production which will damage the reservoir and affect oil well productivity.This study aims to measure how the two factors af...The fluid flow of unconsolidated sandstone reservoir can be affected by compaction and sand production which will damage the reservoir and affect oil well productivity.This study aims to measure how the two factors affect the fluid flow.Firstly,single-phase displacement test was applied to investigate how the permeability changed with compaction.Then two-phase displacement test assessed the influence of compaction on oil production.Finally,the characteristics of fluid flow with compaction and sand production were studied under different water content.The results demonstrate that the reduction of permeability with compaction is irreversible,which will result in lower productivity.In contrast,sand production can increase the permeability at mid and high water content,which slows down the decline of oil production.Generally,the oil well productivity is reduced because of compaction even with sand production,especially when the formation pressure drop varies from 2MPa to 4MPa.Consequently,advance water injection is necessary to keep the formation pressure and oil production during oilfield development of unconsolidated sandstone reservoir.Simultaneously,the study can provide theoretical basis and references for the similar reservoirs.展开更多
Based on relevant urban planning and design standards and a study on successful cases of comprehensive urban design in China, this paper explores a methodology of comprehensive urban design in large scale projects by ...Based on relevant urban planning and design standards and a study on successful cases of comprehensive urban design in China, this paper explores a methodology of comprehensive urban design in large scale projects by applying classical urban design theories and advanced digital technologies. This enables a combination of artful design and scientifi c analysis through the establishment of an urban design indicator system, the application of digital technologies and a multi-leveled control over design contents. The chosen case of the Daqing Comprehensive Urban Design shows that the proposed measures can effectively promote the supervision of comprehensive urban design on both urban morphology and landscape, rapidly convert the urban design outcomes into management rules, and ultimately facilitate the application of the urban design outcomes.展开更多
基金the Undergraduate Creative Program of Central South University,No. 081053358the Education Expenditure of Hunan Provincial Finance Department,No. 2010163the Key Frontier Research Project of Central South University (from 2010 to 2011)
文摘DI-3n-butylphthalide is the active component isolated from the seeds of Apium graveolens Linn. A number of pharmacological and clinical studies have proven that dl-3n-butylphthalide is highly potent and multi-targeted with low toxicity and has a long time-window for the treatment of ischemic cerebrovascular disease. The mechanisms underlying dl-3n-butylphthalide include improving mitochondrial function and microcirculation, inhibiting apoptosis and reducing oxidative stress. Furthermore, dl-3n-butylphthalide may also be promising for the treatment of neurodegenerative diseases, such as Alzheimer＇s disease, vascular dementia and Parkinson＇s disease.
文摘The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA ＋ AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA ＋ AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Hart population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.
基金the Scientific and Technological Foundation of Hunan Public Health Bureau,No. B2003-132
文摘BACKGROUND： Some researches suggest that induced cyclooxygenase-2 （COX-2） can cause brain injury through a series of ways at the phase of cerebral ischemia/hypoxia. Plasminogen activator inhibitor type-1 （PAl-1） is a kind of inhibitor of serine stretch protein enzyme and is able to protect cell surface and microvascular basement membrane from degradation of protease and also protect contact surface among cells so as to maintain intecjrality of tissue structure. However, correlation of protective effect of flunar z ne on bran w th COX-2 and PAl-1 should be studied further. OBJECTTVE ： To observe the effect of flunarizine on expressions of COX-2 and PAl-1 protein in forebrain and degree of brain injury among gerbils after cerebral ischemia. DESIGN ： A randomized controlled animal study SETTING： Department of Neurology, the Second Xiangya Hospital of Central South University; Department of Neurology, Mawangdui Hospital of Hunan Province. MATERIALS： A total of 40 healthy gerbils, of both genders, aged 9 months, weighing （90±10） g, were selected in this study. Anti-COX-2 multi-antibody, anti-PAl-1 multi-antibody, SABC immunohistochemical kit and DAB kit were provided by Wuhan Boster Biological Engineering Co., Ltd.; and flunarizine capsule was provided by Xi＇an Yangsen Pharmaceutical Company （batch number： 041018726, dosage： 5 mg/pill）. METHODS： The experiment was carded out in Laboratory of Mental Disease, Hunan Provincial Geriatrics Institute affiliated by Hunan Provincial Mawangdui Hospital from January 2004 to March 2005. （1） All gerbils were randomly divided into cerebral ischemia group, flunarizine intervention group, sham operation group and norma control group with 10 in each group. Gerbils in normal control group were only cut off their heads. Gerbils in sham operation group were only dissected their bilateral common carotid arteries and sacrificed 1 day later. Gerbils in cerebral ischemia group and flunarizine intervention group were anesthetized, centrally cut open skin of neck, bluntly dissected bilateral common carotid arteries, clipped bilateral common carotid arteries with microvascular clamp for 10 minutes, then reperfused and sacrificed 3 in each group on the 1^st-, 3^rd- and 7^th-day reperfusion. One day before experiment, gerbils in flunarizine intervention group were given 20 mg/kg mixed flunarizine solution. （2） All gerbils were sacrificed in different periods. In addition, forebrain was fixed with 100 g/L formaldehyde, routinely embedded with paraffin, and cut into serial sections with the thickness of 5 μm. Neighboring brain tissues were done with routine HE staining and pathological changes were observed under optic microscope to evaluate the degree of brain injury. Expressions of COX-2 and PAl-1 protein in forebrain were detected with immunohistochemical technique, i.e., numbers of immune positive cells were accounted. （3）Averages of samples were compared with SNK-q test. MAIN OUTCOME MEASURES： Pathological changes of forebrain tissue and expressions of COX-2 and PAl-1 protein in forebrain of gerbils. RESULTS ： All 40 gerbils were involved in the final analysis. （1） Pathological changes of forebrain tissue： Morphologicel structure of cortex tissue was normal in normal control group and sham operation group. At 1 day after ischemia/reperfusion, nerve cells in cortex and hippocampus of forebrain were focal necrosis in cerebra ischemia group, and proliferation of glial cell was slight. In addition, at 3 days after ischemia/reperfusion nerve cells were sheet-like necrosis and proliferation of glial cell was obvious. Meanwhile, at 7 days after is chemia/reperfusion, nerve cells were necrosis in a large area and a lot of glial cells were proliferated. De grees of brain injury were severer in cerebral ischemia group than those in flunarizine intervention group at various time points. （2） Expressions of COX-2 and PAI-1 protein in forebrain： Numbers of COX-2 positive cells in flunarizine intervention group were 62.38±3.38, 33.84±2.48 and 13.82±2.23 at 1, 3 and 7 days after ischemia/reperfusion, respectively, which were less than those in cerebral ischemia group （73.08±2.11, 51.76± 2.38, 23.96±2.86; P〈 0.01）. Numbers of COX-2 positive cells in these two groups were decreased with the lasting time of ischemia/repeffusion. Expressions of PAI-1 in flunarizine intervention group were 14.48±2.0 ,27.44±3.06 and 41.84±2.48 at 1, 3 and 7 days after ischemia/reperfusion, respectively, which were highe than those in cerebral ischemia group （8.48±1.53, 20.93±2.16, 31.12±2.89; P 〈 0.01 ）. Expressions of PAl-1 protein in these two groups were increased with the lasting time of ischemialreperfusion.CONCLUSION ： Ischemia/reperfusion can increase the expressions of COX-2 and PAI-1 protein in forebrain of gerbils; however, pretreatment of flunarizine can down-regulate the expression of COX-2 but up-regulate the expression of PAI-1 protein so as to prevent brain injury after ischemia/reperfusion. Moreover, the preventive effect is time-dependent.
基金This study was supported in part by a grant from the Clinical Research Project of Shanghai Pulmonary Hospital(No.FKLY20010)Young Talents in Shanghai(2019 QNBJ)+1 种基金Shanghai Shuguang Scholar,2021 Science and Technology Think Tank Youth Talent Plan of China Association for Science and Technology,“Dream Tutor”Outstand-ing Young Talents Program(No.fkyq1901)National Key Re-search and Development Program of China(Nos.2021YFF1201200 and 2021YFF1200900).
文摘Pyroptosis is a type of programed cell death that differs from apoptosis,ferroptosis,or necrosis.Numerous studies have reported that it plays a critical role in tumorigenesis and modification of the tumor microenvironment in multiple tumors.In this review,we briefly describe the canonical,non-canonical,and alternative mechanisms of pyroptotic cell death.We also summarize the potential roles of pyroptosis in oncogenesis,tumor development,and lung cancer treatment,including chemotherapy,radiotherapy,targeted therapy,and immunotherapy.Pyrop-tosis has double-edged effects on the modulation of the tumor environment and lung cancer treatment.Further exploration of pyroptosis-based drugs could provide novel therapeutic strategies for lung cancer.
基金The project was supported by the China Important National Science and Technology Specific Projects(2011ZX05024-002-005)the China Important National Science and Technology Specific Projects(2016ZX05025-001-004)the National Natural Science Foundation of China(Grant No.51534006).
文摘The fluid flow of unconsolidated sandstone reservoir can be affected by compaction and sand production which will damage the reservoir and affect oil well productivity.This study aims to measure how the two factors affect the fluid flow.Firstly,single-phase displacement test was applied to investigate how the permeability changed with compaction.Then two-phase displacement test assessed the influence of compaction on oil production.Finally,the characteristics of fluid flow with compaction and sand production were studied under different water content.The results demonstrate that the reduction of permeability with compaction is irreversible,which will result in lower productivity.In contrast,sand production can increase the permeability at mid and high water content,which slows down the decline of oil production.Generally,the oil well productivity is reduced because of compaction even with sand production,especially when the formation pressure drop varies from 2MPa to 4MPa.Consequently,advance water injection is necessary to keep the formation pressure and oil production during oilfield development of unconsolidated sandstone reservoir.Simultaneously,the study can provide theoretical basis and references for the similar reservoirs.
文摘Based on relevant urban planning and design standards and a study on successful cases of comprehensive urban design in China, this paper explores a methodology of comprehensive urban design in large scale projects by applying classical urban design theories and advanced digital technologies. This enables a combination of artful design and scientifi c analysis through the establishment of an urban design indicator system, the application of digital technologies and a multi-leveled control over design contents. The chosen case of the Daqing Comprehensive Urban Design shows that the proposed measures can effectively promote the supervision of comprehensive urban design on both urban morphology and landscape, rapidly convert the urban design outcomes into management rules, and ultimately facilitate the application of the urban design outcomes.
