In Chin.Phys.B 34114704(2025),Eq.(7)and the associated unit notation were incorrect.The correct ones are present here.Since Eq.(7)is an in-built expression in the simulation package,the correction is purely typographi...In Chin.Phys.B 34114704(2025),Eq.(7)and the associated unit notation were incorrect.The correct ones are present here.Since Eq.(7)is an in-built expression in the simulation package,the correction is purely typographical and does not affect the simulation procedure,numerical results,or the conclusions.展开更多
Quantum key distribution(QKD)achieves information-theoretic security based on quantum mechanics principles,where single-photon detectors(SPDs)serve as critical components.This study focuses on the sinusoidal gated SPD...Quantum key distribution(QKD)achieves information-theoretic security based on quantum mechanics principles,where single-photon detectors(SPDs)serve as critical components.This study focuses on the sinusoidal gated SPDs widely used in high-speed QKD systems.We investigate the mechanisms underlying the rising-edge jitter in detection signals,identifying contributions from factors such as the temporal width of injected optical pulses,avalanche generation processes,avalanche signal extraction,and pulse discrimination.To address the issue of excessive jitter-induced bit errors,we propose a retiming scheme that utilizes coincidence signals synchronized with the sinusoidal gating signal.This approach effectively suppresses detection signal jitter and reduces the after-pulse probability of the detector.Experimental validation using a high-precision time-to-digital converter(TDC)demonstrates a significant reduction in the rising-edge jitter distribution after applying the suppression scheme.The proposed method features clear principles and straightforward engineering implementation,avoiding direct interference with the detector’s operational processes.The designed high-speed sinusoidal gated InGaAs/InP SPD operates at 1.25 GHz,achieving a remarkable reduction in after-pulse probability from 10.7%(without jitter suppression)to 0.72%,thereby enhancing the overall performance of QKD systems.展开更多
BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to p...BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to play a central role in disease pathogenesis.AIM To investigate the role of TSC22D1 in NAFLD fibrosis through its regulation of LSEC dysfunction and macrophage polarization.METHODS We analysed single-cell transcriptomic data(GSE129516)from NASH and normal INTRODUCTION Non-alcoholic fatty liver disease(NAFLD)is a global health issue associated with increasing rates of obesity and metabolic syndrome.NAFLD encompasses a spectrum of conditions,ranging from simple steatosis to more severe manifestations such as non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma.Liver fibrosis represents a critical stage in NAFLD progression because of its strong association with impaired liver function,progression to end-stage liver disease,and increased disease-related mortality[1].The pathogenesis of NAFLD is multifactorial and involves complex interactions between genetic predispositions,insulin resistance,dietary factors,and chronic inflammation[2].Liver sinusoidal endothelial cells(LSECs),which are highly specialized endothelial cells lining the hepatic sinusoids,critically contribute to both the pathogenesis and progression of NAFLD[3,4].In NAFLD,LSECs undergo structural alterations such as reduced fenestrations,which impair hepatic microcirculation and hinder the exchange of lipids and other substances,thereby promoting lipid accumulation in hepatocytes[5].Furthermore,dysfunctional LSECs exacerbate hepatic inflammation and fibrogenesis by releasing pro-inflammatory cytokines and fibrogenic mediators,such as transforming growth factor-β(TGF-β).These factors activate hepatic stellate cells(HSCs),resulting in the pathological accumulation of extracellular matrix components[6].LSECs are also highly susceptible to oxidative stress,further aggravating hepatic injury[7,8].Importantly,LSECs influence macrophage polarization by producing chemotactic and immunomodulatory factors,thereby promoting the recruitment and activation of M1-type pro-inflammatory CONCLUSION In conclusion,this study provides a comprehensive understanding of the role of TSC22D1 in the pathogenesis of NAFLD fibrosis.We elucidated the mechanisms through which TSC22D1 drives LSEC microvascularization and EndMT,as well as its role in promoting the secretion of TWEAK,which induces macrophage polarization towards the M1 phenotype.These findings offer novel insights into the pathophysiology of NAFLD,particularly the interplay between endothelial dysfunction,inflammation,and fibrosis.Importantly,our results highlight the potential of TSC22D1 as a therapeutic target for NAFLD.Future research should focus on validating these mechanisms in human clinical cohorts and deve-loping targeted interventions,such as TSC22D1 inhibitors or modulators of the TWEAK/FN14 signalling pathway,to translate these findings into effective treatments for NAFLD progression to fibrosis.展开更多
Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS be...Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.展开更多
Sinusoidal obstruction syndrome(SOS), previously known as hepatic veno-occlusive disease, is a rare disorder in solid organ transplant patients, and is an uncommon complication after liver transplantation. Severe SOS ...Sinusoidal obstruction syndrome(SOS), previously known as hepatic veno-occlusive disease, is a rare disorder in solid organ transplant patients, and is an uncommon complication after liver transplantation. Severe SOS with hepatic failure causes considerable mortality. Tacrolimus has been reported to be an offending agent, which potentially plays a role in the pathophysiological process of SOS. SOS due to tacrolimus has been reported in lung and pancreatic transplantations, but has never been described in a liver transplant recipient. Herein, we present a case of SOS after liver transplantation, which was possibly related to tacrolimus. A 27-year-old man developed typical symptoms of SOS with painful hepatomegaly, ascites and jaundice after liver transplantation, which regressed following withdrawal of tacrolimus. By excluding other possible predisposing factors, we concluded that tacrolimus was the most likely cause of SOS.展开更多
The linear systems affected by additive external sinusoidal disturbances is studied. The problem is to damp this forced oscillation in an optimal fashion. The main result of this paper is a new design approach is prop...The linear systems affected by additive external sinusoidal disturbances is studied. The problem is to damp this forced oscillation in an optimal fashion. The main result of this paper is a new design approach is proposed of realizable feedforward and feedback optimal control law for a linear time invariant system with sinusoidal disturbances. The algorithm of solving the optimal control law is given. It is shown that the control law is easily realized and is robust with respect to errors produced by the external sinusoidal disturbances through simulation results.展开更多
The hepatic sinusoids are lined by a unique population of hepatic sinusoidal endothelial cells (HSEC), which is one of the first hepatic cell populations to come into contact with blood components. However, HSEC are n...The hepatic sinusoids are lined by a unique population of hepatic sinusoidal endothelial cells (HSEC), which is one of the first hepatic cell populations to come into contact with blood components. However, HSEC are not simply barrier cells that restrict the access of blood- borne compounds to the parenchyma. They are func- tionally specialised endothelial cells that have complex roles, including not only receptor-mediated clearance of endotoxin, bacteria and other compounds, but also the regulation of inflammation, leukocyte recruitment and host immune responses to pathogens. Thus understand- ing the differentiation and function of HSEC is critical for the elucidation of liver biology and pathophysiology. This article reviews methods for isolating and studying human hepatic endothelial cell populations using in vitro models. We also discuss the expression and functions of phe- notypic markers, such as the presence of fenestrations and expression of VAP-1, Stabilin-1, L-SIGN, which can be used to identify sinusoidal endothelium and to permit discrimination from vascular and lymphatic endothelial cells.展开更多
Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and c...Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix,which is closely related to liver sinusoidal endothelial cells(LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor,which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein,we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.展开更多
Background and objective： Hepatic sinusoidal obstruction syndrome （HSOS） is characterized by painful hepatomegaly, ascites, increased body weight, and jaundice. Gynura segetum （Compositae）, a plant widely used in...Background and objective： Hepatic sinusoidal obstruction syndrome （HSOS） is characterized by painful hepatomegaly, ascites, increased body weight, and jaundice. Gynura segetum （Compositae）, a plant widely used in Chinese traditional medicine, often leads to the development of HSOS. However, the mechanism is unclear. The aim was to study the role of matrix metalloproteinase-9 （MMP-9） in the onset of HSOS induced by Gynura segetum. Methods： Twenty-five male Sprague-Dawley rats were randomly divided into two groups. Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks; five control rats were exposed to tap water alone. Liver sections were evaluated by light microscopy with a modified scoring system. Routine transmission electron microscopy （TEM） methods were used to evaluate the ultrastructual features of fixed liver tissue, and blood samples were collected to determine liver enzyme concentrations. MMP-9 expression was assessed by both immunohisto- chemical staining and enzyme-linked immunosorbent assay （ELISA） methods. Results： A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract. The treated rats presented clinical symptoms and the histopathological manifestation of HSOS, including abnormal liver enzyme concentrations （alanine aminotransferase （ALT）： （84.8＋13.62） vs. （167.0±72.63） U/L, P〈0.05; aspartate aminotransferase （AST）： （27.6±6.31） vs. （232.8±108.58） U/L, P〈0.05）. Hematoxylin and eosin （H＆E） staining and TEM together revealed deposition of red blood cells, the damage and destruction of hepatic sinusoidal endothelial cells, collapse of hepatic sinusoids, hem- orrhage of subendothelial cells, atrophy and destruction of hepatocytes, etc. Compared with controls, the expression of MMP-9 in the blood sample, the lung and liver tissues of HSOS rats was increased. Conclusions： MMP-9 may have an important role in early patholoclical chanqes of HSOS, and thus the onset of the disease.展开更多
Important advances have been made in research into the mechanism of alcoholic liver disease(ALD)over the past few years,but the role of liver sinusoidal endothelial cell(LSEC)in ALD has not been elucidated adequately....Important advances have been made in research into the mechanism of alcoholic liver disease(ALD)over the past few years,but the role of liver sinusoidal endothelial cell(LSEC)in ALD has not been elucidated adequately.This study was undertaken to investigate the effect of ethanol on fenestrae of LSECs in rats.METHODS:A rat model of alcoholic liver disease was established by means of direct intragastric instillation of ethanol.Fifty-five rats of experimental(35 rats)and control(20)groups were sacrificed at the end of 4,8,12 weeks respectively,and also at the end of 12-week abstinence.After heart perfusion,the liver tissue was fixed and stained with hematoxylin and eosin for observation of serial changes of LSEC-fenestrae under a transmission electron microscope.RESULTS:Normal LESC was flat with a nucleus and organelles arranged regularly.The distal cytoplasm displayed as a lamina with many fenestrae,lacking the basement membrane(BM)underneath the endothelium.At the end of 4-week alcohol feeding,the number of fenestrae decreased at the distal cytoplasm in some LSECs,without the formation of the BM underneath the endothelium.At the end of 8 weeks,the number of fenestrae decreased significantly or even disappeared.The BM began to develop incompletely underneath the endothelium,while the active fibroblast appeared.At the end of 12 weeks,the number of fenestrae decreased more significantly and the complete BM could even be seen.But the changes were mostly limited in the single or adjoining sinus,and fibrosis was scarcely formed.At the end of 12-week abstinence,defenestration and formation of the endothelial BM lightened significantly.CONCLUSIONS:Defenestration and formation of the BM in LSECs develop gradually with the chronic stimulation of ethanol.Hepatic sinusoidal capillarization and fibrosis will be seen if their state is more serious.These early changes,i.e.,limited and regional defenestration and capillarization may be the basis of alcoholic peri-fibrosis.This kind of he-patic fibrosis is reversible after removal of etiological factors.展开更多
文摘In Chin.Phys.B 34114704(2025),Eq.(7)and the associated unit notation were incorrect.The correct ones are present here.Since Eq.(7)is an in-built expression in the simulation package,the correction is purely typographical and does not affect the simulation procedure,numerical results,or the conclusions.
基金supported by the Major Scientific and Technological Special Project of Anhui Province(202103a13010004)the Major Scientific and Technological Special Project of Hefei City(2021DX007)the Manufacturing Industry Project of Attracting Talents and Wisdom of Anhui Province(JB24179).
文摘Quantum key distribution(QKD)achieves information-theoretic security based on quantum mechanics principles,where single-photon detectors(SPDs)serve as critical components.This study focuses on the sinusoidal gated SPDs widely used in high-speed QKD systems.We investigate the mechanisms underlying the rising-edge jitter in detection signals,identifying contributions from factors such as the temporal width of injected optical pulses,avalanche generation processes,avalanche signal extraction,and pulse discrimination.To address the issue of excessive jitter-induced bit errors,we propose a retiming scheme that utilizes coincidence signals synchronized with the sinusoidal gating signal.This approach effectively suppresses detection signal jitter and reduces the after-pulse probability of the detector.Experimental validation using a high-precision time-to-digital converter(TDC)demonstrates a significant reduction in the rising-edge jitter distribution after applying the suppression scheme.The proposed method features clear principles and straightforward engineering implementation,avoiding direct interference with the detector’s operational processes.The designed high-speed sinusoidal gated InGaAs/InP SPD operates at 1.25 GHz,achieving a remarkable reduction in after-pulse probability from 10.7%(without jitter suppression)to 0.72%,thereby enhancing the overall performance of QKD systems.
基金Supported by the Changzhou Science and Techology Program,No.CJ20241048Changzhou High-Level Medical Talents Training Project,No.2022CZBJ105+1 种基金Development Foundation of the Affiliated Hospital of Xuzhou Medical University,No.XYFC202304 and No.XYFM202307The Open Project of Jiangsu Provincial Key Laboratory of Laboratory Medicine,No.JSKLM-Z-2024-002.
文摘BACKGROUND The progression of non-alcoholic fatty liver disease(NAFLD)to non-alcoholic steatohepatitis(NASH)and liver fibrosis remains poorly understood,though liver sinusoidal endothelial cells(LSECs)are thought to play a central role in disease pathogenesis.AIM To investigate the role of TSC22D1 in NAFLD fibrosis through its regulation of LSEC dysfunction and macrophage polarization.METHODS We analysed single-cell transcriptomic data(GSE129516)from NASH and normal INTRODUCTION Non-alcoholic fatty liver disease(NAFLD)is a global health issue associated with increasing rates of obesity and metabolic syndrome.NAFLD encompasses a spectrum of conditions,ranging from simple steatosis to more severe manifestations such as non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma.Liver fibrosis represents a critical stage in NAFLD progression because of its strong association with impaired liver function,progression to end-stage liver disease,and increased disease-related mortality[1].The pathogenesis of NAFLD is multifactorial and involves complex interactions between genetic predispositions,insulin resistance,dietary factors,and chronic inflammation[2].Liver sinusoidal endothelial cells(LSECs),which are highly specialized endothelial cells lining the hepatic sinusoids,critically contribute to both the pathogenesis and progression of NAFLD[3,4].In NAFLD,LSECs undergo structural alterations such as reduced fenestrations,which impair hepatic microcirculation and hinder the exchange of lipids and other substances,thereby promoting lipid accumulation in hepatocytes[5].Furthermore,dysfunctional LSECs exacerbate hepatic inflammation and fibrogenesis by releasing pro-inflammatory cytokines and fibrogenic mediators,such as transforming growth factor-β(TGF-β).These factors activate hepatic stellate cells(HSCs),resulting in the pathological accumulation of extracellular matrix components[6].LSECs are also highly susceptible to oxidative stress,further aggravating hepatic injury[7,8].Importantly,LSECs influence macrophage polarization by producing chemotactic and immunomodulatory factors,thereby promoting the recruitment and activation of M1-type pro-inflammatory CONCLUSION In conclusion,this study provides a comprehensive understanding of the role of TSC22D1 in the pathogenesis of NAFLD fibrosis.We elucidated the mechanisms through which TSC22D1 drives LSEC microvascularization and EndMT,as well as its role in promoting the secretion of TWEAK,which induces macrophage polarization towards the M1 phenotype.These findings offer novel insights into the pathophysiology of NAFLD,particularly the interplay between endothelial dysfunction,inflammation,and fibrosis.Importantly,our results highlight the potential of TSC22D1 as a therapeutic target for NAFLD.Future research should focus on validating these mechanisms in human clinical cohorts and deve-loping targeted interventions,such as TSC22D1 inhibitors or modulators of the TWEAK/FN14 signalling pathway,to translate these findings into effective treatments for NAFLD progression to fibrosis.
基金Supported by National Natural Science Foundation of China,No.81570555 and No.81770582
文摘Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.
基金Supported by National Natural Science Foundation of China,No.81373160
文摘Sinusoidal obstruction syndrome(SOS), previously known as hepatic veno-occlusive disease, is a rare disorder in solid organ transplant patients, and is an uncommon complication after liver transplantation. Severe SOS with hepatic failure causes considerable mortality. Tacrolimus has been reported to be an offending agent, which potentially plays a role in the pathophysiological process of SOS. SOS due to tacrolimus has been reported in lung and pancreatic transplantations, but has never been described in a liver transplant recipient. Herein, we present a case of SOS after liver transplantation, which was possibly related to tacrolimus. A 27-year-old man developed typical symptoms of SOS with painful hepatomegaly, ascites and jaundice after liver transplantation, which regressed following withdrawal of tacrolimus. By excluding other possible predisposing factors, we concluded that tacrolimus was the most likely cause of SOS.
文摘The linear systems affected by additive external sinusoidal disturbances is studied. The problem is to damp this forced oscillation in an optimal fashion. The main result of this paper is a new design approach is proposed of realizable feedforward and feedback optimal control law for a linear time invariant system with sinusoidal disturbances. The algorithm of solving the optimal control law is given. It is shown that the control law is easily realized and is robust with respect to errors produced by the external sinusoidal disturbances through simulation results.
文摘The hepatic sinusoids are lined by a unique population of hepatic sinusoidal endothelial cells (HSEC), which is one of the first hepatic cell populations to come into contact with blood components. However, HSEC are not simply barrier cells that restrict the access of blood- borne compounds to the parenchyma. They are func- tionally specialised endothelial cells that have complex roles, including not only receptor-mediated clearance of endotoxin, bacteria and other compounds, but also the regulation of inflammation, leukocyte recruitment and host immune responses to pathogens. Thus understand- ing the differentiation and function of HSEC is critical for the elucidation of liver biology and pathophysiology. This article reviews methods for isolating and studying human hepatic endothelial cell populations using in vitro models. We also discuss the expression and functions of phe- notypic markers, such as the presence of fenestrations and expression of VAP-1, Stabilin-1, L-SIGN, which can be used to identify sinusoidal endothelium and to permit discrimination from vascular and lymphatic endothelial cells.
基金Supported by the Young Elite Scientists Sponsorship Program by CAST,No.2016QNRC001Beijing Natural Science Foundation,No.7172187
文摘Cirrhosis develops from liver fibrosis and is the severe pathological stage of all chronic liver injury. Cirrhosis caused by hepatitis B virus and hepatitis C virus infection is especially common. Liver fibrosis and cirrhosis involve excess production of extracellular matrix,which is closely related to liver sinusoidal endothelial cells(LSECs). Damaged LSECs can synthesize transforming growth factor-beta and platelet-derived growth factor,which activate hepatic stellate cells and facilitate the synthesis of extracellular matrix. Herein,we highlight the angiogenic cytokines of LSECs related to liver fibrosis and cirrhosis at different stages and focus on the formation and development of liver fibrosis and cirrhosis. Inhibition of LSEC angiogenesis and antiangiogenic therapy are described in detail. Targeting LSECs has high therapeutic potential for liver diseases. Further understanding of the mechanism of action will provide stronger evidence for the development of anti-LSEC drugs and new directions for diagnosis and treatment of liver diseases.
基金Project supported by the National Natural Science Foundation of China (No.30925033)the Administration of Traditional Chinese Medicine of Zhejiang Province (No.2007ZA016),China
文摘Background and objective： Hepatic sinusoidal obstruction syndrome （HSOS） is characterized by painful hepatomegaly, ascites, increased body weight, and jaundice. Gynura segetum （Compositae）, a plant widely used in Chinese traditional medicine, often leads to the development of HSOS. However, the mechanism is unclear. The aim was to study the role of matrix metalloproteinase-9 （MMP-9） in the onset of HSOS induced by Gynura segetum. Methods： Twenty-five male Sprague-Dawley rats were randomly divided into two groups. Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks; five control rats were exposed to tap water alone. Liver sections were evaluated by light microscopy with a modified scoring system. Routine transmission electron microscopy （TEM） methods were used to evaluate the ultrastructual features of fixed liver tissue, and blood samples were collected to determine liver enzyme concentrations. MMP-9 expression was assessed by both immunohisto- chemical staining and enzyme-linked immunosorbent assay （ELISA） methods. Results： A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract. The treated rats presented clinical symptoms and the histopathological manifestation of HSOS, including abnormal liver enzyme concentrations （alanine aminotransferase （ALT）： （84.8＋13.62） vs. （167.0±72.63） U/L, P〈0.05; aspartate aminotransferase （AST）： （27.6±6.31） vs. （232.8±108.58） U/L, P〈0.05）. Hematoxylin and eosin （H＆E） staining and TEM together revealed deposition of red blood cells, the damage and destruction of hepatic sinusoidal endothelial cells, collapse of hepatic sinusoids, hem- orrhage of subendothelial cells, atrophy and destruction of hepatocytes, etc. Compared with controls, the expression of MMP-9 in the blood sample, the lung and liver tissues of HSOS rats was increased. Conclusions： MMP-9 may have an important role in early patholoclical chanqes of HSOS, and thus the onset of the disease.
文摘Important advances have been made in research into the mechanism of alcoholic liver disease(ALD)over the past few years,but the role of liver sinusoidal endothelial cell(LSEC)in ALD has not been elucidated adequately.This study was undertaken to investigate the effect of ethanol on fenestrae of LSECs in rats.METHODS:A rat model of alcoholic liver disease was established by means of direct intragastric instillation of ethanol.Fifty-five rats of experimental(35 rats)and control(20)groups were sacrificed at the end of 4,8,12 weeks respectively,and also at the end of 12-week abstinence.After heart perfusion,the liver tissue was fixed and stained with hematoxylin and eosin for observation of serial changes of LSEC-fenestrae under a transmission electron microscope.RESULTS:Normal LESC was flat with a nucleus and organelles arranged regularly.The distal cytoplasm displayed as a lamina with many fenestrae,lacking the basement membrane(BM)underneath the endothelium.At the end of 4-week alcohol feeding,the number of fenestrae decreased at the distal cytoplasm in some LSECs,without the formation of the BM underneath the endothelium.At the end of 8 weeks,the number of fenestrae decreased significantly or even disappeared.The BM began to develop incompletely underneath the endothelium,while the active fibroblast appeared.At the end of 12 weeks,the number of fenestrae decreased more significantly and the complete BM could even be seen.But the changes were mostly limited in the single or adjoining sinus,and fibrosis was scarcely formed.At the end of 12-week abstinence,defenestration and formation of the endothelial BM lightened significantly.CONCLUSIONS:Defenestration and formation of the BM in LSECs develop gradually with the chronic stimulation of ethanol.Hepatic sinusoidal capillarization and fibrosis will be seen if their state is more serious.These early changes,i.e.,limited and regional defenestration and capillarization may be the basis of alcoholic peri-fibrosis.This kind of he-patic fibrosis is reversible after removal of etiological factors.
