Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this s...Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups(which received physiological saline), the doses of KXS(0.7, 1.4 and 2.8 g/kg per day) and donepezil(3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following.(1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze.(2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze.(3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies.(4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus.(5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.展开更多
Yielding behaviors of waxy crude oil is one of the key issues of flow assurance challenges. The yielding of waxy crude under constant stress is actually a creep process of strain accumulation to structural failure,to ...Yielding behaviors of waxy crude oil is one of the key issues of flow assurance challenges. The yielding of waxy crude under constant stress is actually a creep process of strain accumulation to structural failure,to describe the process completely and accurately is the basis of numerical simulation of restart process of the pipeline. The creep and yield behaviors of two gelled waxy crudes were investigated experimentally under different constant applied stresses. The results clearly show that the creep process of waxy crude is related to the applied stress and time. The greater the applied stress, and the longer the loaded time, the more obvious the nonlinear features. Based on the fractional calculus theory, a fractional viscous element was developed to describe the decelerated and steady creep process of gelled waxy crude. On the basis of the damage theory, an elastic damage element was proposed to describe the accelerated creep after the yielding. According to the idea of mechanical analogy, a nonlinear creep model was established by a fractional viscous element, an elastic damaged element, and an elastic element in series, which can accurately describe the whole creep and yielding process of gelled waxy crude.展开更多
Exposing waxy oils to an electric field may significantly improve their cold flowability.Our previous study has shown that interfacial polarization,i.e.,charged particle accumulation on the wax particle surface,is the...Exposing waxy oils to an electric field may significantly improve their cold flowability.Our previous study has shown that interfacial polarization,i.e.,charged particle accumulation on the wax particle surface,is the primary mechanism of the electrorheological behavior of waxy oils.However,the way that charged particles interact with wax particles under an electric field remains unknown.In this study,we found no viscosity and impedance change for two waxy crude oils after their exposure to a high-voltage electric field.However,the yield stresses were reduced obviously.We thus proposed that the collision of colloidal particles such as resins and asphaltenes with the wax particles could be an essential mechanism that the wax particle structure was weakened.To verify this hypothesis,a series of ad hoc experiments were carried out,i.e.,by performing electrorheological tests on model waxy oils containing additives removable under an electric field,including electrically-neutral colloidal particles(Fe3O4),charged colloidal particles(resins),and oil-soluble electrolyte(C22H14CoO4),respectively,and demonstrated that upon application of a high-voltage electric field,charged particles in a waxy oil may move and thus collide with wax particles,and consequently adhere to the wax particle surface.The particle collision results in damage to the wax particle network,and the electrostatic repulsion arising from the adhesion of the charged particle on the wax particle diminishes attraction between wax particles.This study clarifies the process of interfacial polarization.展开更多
Secondary degeneration occurs commonly in the central nervous system after traumatic injuries and following acute and chronic diseases, including glaucoma. A constellation of mechanisms have been shown to be associate...Secondary degeneration occurs commonly in the central nervous system after traumatic injuries and following acute and chronic diseases, including glaucoma. A constellation of mechanisms have been shown to be associated with secondary degeneration including apoptosis, necrosis, autophagy, oxidative stress, excitotoxicity, derangements in ionic homeostasis and calcium influx. Glial cells, such as microglia, astrocytes and oligodendrocytes, have also been demon- strated to take part in the process of secondary injury. Partial optic nerve transection is a useful model which was established about 13 years ago. The merit of this model compared with other optic nerve injury models used for glaucoma study, including complete optic nerve transection model and optic nerve crush model, is the possibility to separate primary degeneration from secondary degeneration in location. Therefore, it provides a good tool for the study of secondary degeneration. This review will focus on the research progress of the mechanisms of secondary degeneration using partial optic nerve transection model.展开更多
Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegener...Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegenerative diseases, including glaucoma. However, whether running can delay primary or secondary degeneration or both of them was not clear. Partial optic nerve transection model is a valuable glaucoma model for studying both primary and secondary degeneration because it can separate primary(mainly in the superior retina) from secondary(mainly in the inferior retina) degeneration. Therefore, we compared the survival of retinal ganglion cells between Sprague-Dawley rat runners and non-runners both in the superior and inferior retinas. Excitotoxicity, oxidative stress, and apoptosis are involved in the degeneration of retinal ganglion cells in glaucoma. So we also used western immunoblotting to compare the expression of some proteins involved in apoptosis(phospho-c-Jun N-terminal kinases, p-JNKs), oxidative stress(manganese superoxide dismutase, MnSOD) and excitotoxicity(glutamine synthetase) between runners and non-runners after partial optic nerve transection. Results showed that voluntary running delayed the death of retinal ganglion cells vulnerable to primary degeneration but not those to secondary degeneration. In addition, voluntary running decreased the expression of glutamine synthetase, but not the expression of p-JNKs and MnSOD in the superior retina after partial optic nerve transection. These results illustrated that primary degeneration of retinal ganglion cells might be mainly related with excitotoxicity rather than oxidative stress; and the voluntary running could down-regulate excitotoxicity to delay the primary degeneration of retinal ganglion cells after partial optic nerve transection.展开更多
Objective:Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis.This phase 3,multicenter,randomized,double-blind,placebo-c...Objective:Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis.This phase 3,multicenter,randomized,double-blind,placebo-controlled trial(NCT03364309;registered December 6,2017)evaluated the safety and efficacy of ixekizumab in Chinese patients with moderate-to-severe psoriasis.Methods:438 patients were randomized 2:2:1 to 80 mg ixekizumab every 2 weeks(IXE Q2W,n=176),80 mg ixekizumab every 4 weeks(IXE Q4W,n=174),or placebo(n=88).Efficacy was assessed by evaluating the static Physician’s Global Assessment score of 0 or 1(sPGA[0,1])and Psoriasis Area and Severity Index(PASI)75/90/100 responses,and nonresponder imputation was used for handling missing data.The safety profile was evaluated by assessing treatment emergent adverse events(AEs)and serious AEs.Results:At week 12,the sPGA(0,1)response rates were 3.4%,79.9%,and 86.4%in the placebo,IXE Q4W,and IXE Q2W groups,respectively.The PASI 75/90/100 response rates were 8.0%/2.3%/0.0%,87.4%/75.9%/29.3%,and 93.8%/82.4%/33.0%in the placebo,IXE Q4W,and IXE Q2W groups,respectively.Ixekizumab led to rapid PASI 50 responses,as early as week 1,whereas PASI 75 and sPGA(0,1)responses were observed from week 2.sPGA(0,1)and sPGA(0)responses were maintained through week 60 in a higher proportion of patients receiving IXE Q4W vs.placebo.The safety profile was consistent with previous studies of ixekizumab in psoriasis.Conclusion:Ixekizumab showed a rapid onset of action and high efficacy that was maintained through 60 weeks and was well tolerated with no unexpected AEs,in Chinese patients with moderate-to-severe plaque psoriasis.展开更多
基金supported by the National Natural Science Foundation of China,No.81473740,81673627,81673717(to QW)Guangzhou Science Technology and Innovation Commission Technology Research Projects,China,No.2018050100(to QW)+3 种基金the Foundation for Characteristic Innovation of Educational Commission of Guangdong Province,China,Grant No.2016KTSCX011(to SHF)the Open Tending Project for Construction of High-Level University,Guangzhou University of Chinese Medicine,China,No.34 and 118,2017(to SHF)the Technology Platform of Clinical Trials on New Traditional Medicine,China,No.2012ZX09303009-003(to WXL)the Technology Platform of Clinical Evaluation on New Traditional Medicine,China,No.2008ZX09312-021(to WXL)
文摘Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups(which received physiological saline), the doses of KXS(0.7, 1.4 and 2.8 g/kg per day) and donepezil(3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following.(1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze.(2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze.(3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies.(4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus.(5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.
基金the financial support from the National Natural Science Foundation of China (No.52174066)。
文摘Yielding behaviors of waxy crude oil is one of the key issues of flow assurance challenges. The yielding of waxy crude under constant stress is actually a creep process of strain accumulation to structural failure,to describe the process completely and accurately is the basis of numerical simulation of restart process of the pipeline. The creep and yield behaviors of two gelled waxy crudes were investigated experimentally under different constant applied stresses. The results clearly show that the creep process of waxy crude is related to the applied stress and time. The greater the applied stress, and the longer the loaded time, the more obvious the nonlinear features. Based on the fractional calculus theory, a fractional viscous element was developed to describe the decelerated and steady creep process of gelled waxy crude. On the basis of the damage theory, an elastic damage element was proposed to describe the accelerated creep after the yielding. According to the idea of mechanical analogy, a nonlinear creep model was established by a fractional viscous element, an elastic damaged element, and an elastic element in series, which can accurately describe the whole creep and yielding process of gelled waxy crude.
基金financial support from the National Natural Science Foundation of China(No.52174066,No.51534007).
文摘Exposing waxy oils to an electric field may significantly improve their cold flowability.Our previous study has shown that interfacial polarization,i.e.,charged particle accumulation on the wax particle surface,is the primary mechanism of the electrorheological behavior of waxy oils.However,the way that charged particles interact with wax particles under an electric field remains unknown.In this study,we found no viscosity and impedance change for two waxy crude oils after their exposure to a high-voltage electric field.However,the yield stresses were reduced obviously.We thus proposed that the collision of colloidal particles such as resins and asphaltenes with the wax particles could be an essential mechanism that the wax particle structure was weakened.To verify this hypothesis,a series of ad hoc experiments were carried out,i.e.,by performing electrorheological tests on model waxy oils containing additives removable under an electric field,including electrically-neutral colloidal particles(Fe3O4),charged colloidal particles(resins),and oil-soluble electrolyte(C22H14CoO4),respectively,and demonstrated that upon application of a high-voltage electric field,charged particles in a waxy oil may move and thus collide with wax particles,and consequently adhere to the wax particle surface.The particle collision results in damage to the wax particle network,and the electrostatic repulsion arising from the adhesion of the charged particle on the wax particle diminishes attraction between wax particles.This study clarifies the process of interfacial polarization.
基金supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region,China(HKU 776109M)supported by the Fundamental Research Funds for the Central Universities Grant 21609101
文摘Secondary degeneration occurs commonly in the central nervous system after traumatic injuries and following acute and chronic diseases, including glaucoma. A constellation of mechanisms have been shown to be associated with secondary degeneration including apoptosis, necrosis, autophagy, oxidative stress, excitotoxicity, derangements in ionic homeostasis and calcium influx. Glial cells, such as microglia, astrocytes and oligodendrocytes, have also been demon- strated to take part in the process of secondary injury. Partial optic nerve transection is a useful model which was established about 13 years ago. The merit of this model compared with other optic nerve injury models used for glaucoma study, including complete optic nerve transection model and optic nerve crush model, is the possibility to separate primary degeneration from secondary degeneration in location. Therefore, it provides a good tool for the study of secondary degeneration. This review will focus on the research progress of the mechanisms of secondary degeneration using partial optic nerve transection model.
基金supported by the National Natural Science Foundation of China,No.81501091(to HYL)Natural Science Foundation of Guangdong Province of China,No.2015A030310201(to HYL)+4 种基金Medical Scientific Research Foundation of Guangdong Province of China,No.A2015393(to HYL)funds of Leading Talents of Guangdong Province of China,No.2013(to KFS)Programme of Introducing Talents of Discipline to Universities,No.B14036(to KFS)National Basic Research Program of China(973 Program),No.2015CB351800(to KFS)Fundamental Research Funds for the Central Universities,No.21609101(to KFS)
文摘Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegenerative diseases, including glaucoma. However, whether running can delay primary or secondary degeneration or both of them was not clear. Partial optic nerve transection model is a valuable glaucoma model for studying both primary and secondary degeneration because it can separate primary(mainly in the superior retina) from secondary(mainly in the inferior retina) degeneration. Therefore, we compared the survival of retinal ganglion cells between Sprague-Dawley rat runners and non-runners both in the superior and inferior retinas. Excitotoxicity, oxidative stress, and apoptosis are involved in the degeneration of retinal ganglion cells in glaucoma. So we also used western immunoblotting to compare the expression of some proteins involved in apoptosis(phospho-c-Jun N-terminal kinases, p-JNKs), oxidative stress(manganese superoxide dismutase, MnSOD) and excitotoxicity(glutamine synthetase) between runners and non-runners after partial optic nerve transection. Results showed that voluntary running delayed the death of retinal ganglion cells vulnerable to primary degeneration but not those to secondary degeneration. In addition, voluntary running decreased the expression of glutamine synthetase, but not the expression of p-JNKs and MnSOD in the superior retina after partial optic nerve transection. These results illustrated that primary degeneration of retinal ganglion cells might be mainly related with excitotoxicity rather than oxidative stress; and the voluntary running could down-regulate excitotoxicity to delay the primary degeneration of retinal ganglion cells after partial optic nerve transection.
基金This study was sponsored by Eli Lilly, the manufacturer/licensee of ixekizumab.
文摘Objective:Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A and is approved for treating moderate-to-severe psoriasis.This phase 3,multicenter,randomized,double-blind,placebo-controlled trial(NCT03364309;registered December 6,2017)evaluated the safety and efficacy of ixekizumab in Chinese patients with moderate-to-severe psoriasis.Methods:438 patients were randomized 2:2:1 to 80 mg ixekizumab every 2 weeks(IXE Q2W,n=176),80 mg ixekizumab every 4 weeks(IXE Q4W,n=174),or placebo(n=88).Efficacy was assessed by evaluating the static Physician’s Global Assessment score of 0 or 1(sPGA[0,1])and Psoriasis Area and Severity Index(PASI)75/90/100 responses,and nonresponder imputation was used for handling missing data.The safety profile was evaluated by assessing treatment emergent adverse events(AEs)and serious AEs.Results:At week 12,the sPGA(0,1)response rates were 3.4%,79.9%,and 86.4%in the placebo,IXE Q4W,and IXE Q2W groups,respectively.The PASI 75/90/100 response rates were 8.0%/2.3%/0.0%,87.4%/75.9%/29.3%,and 93.8%/82.4%/33.0%in the placebo,IXE Q4W,and IXE Q2W groups,respectively.Ixekizumab led to rapid PASI 50 responses,as early as week 1,whereas PASI 75 and sPGA(0,1)responses were observed from week 2.sPGA(0,1)and sPGA(0)responses were maintained through week 60 in a higher proportion of patients receiving IXE Q4W vs.placebo.The safety profile was consistent with previous studies of ixekizumab in psoriasis.Conclusion:Ixekizumab showed a rapid onset of action and high efficacy that was maintained through 60 weeks and was well tolerated with no unexpected AEs,in Chinese patients with moderate-to-severe plaque psoriasis.