In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a ...In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.展开更多
Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, tr...Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, transient outward potassium current （/to）, delayed rectifier current （/K）, and inward rectifier potassium currents （/K1） in isolated ventricular myocytes. Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes. Results SSYX decreased peak Na by （44.84±7.65）% from 27.21±5.35 to 14.88±2..75 pA/pF （n=-5, P〈0.05）. The medicine significantly inhibited the /Ca,L. At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak/Ca,L was reduced by （19.22±1.10）%, （44.82±6.50）% and （50.69±5.64）%, respectively （n=5, all P〈0.05）. SSYX lifted the I-V curve of both /Na and /Ca,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of /to by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of /K was decreased by （30.77±1.11）% （n=5, P〈0.05） at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of /K was also inhibited. Similar to the effect on /K, the SSYX inhibited /K1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property. Conclusions The experiments revealed that SSYX could block multiple ion channels such as /Na /Ca,L, /k, /to and /K1, which may change the action potential duration and contribute to some of its antiarrhythmic effects.展开更多
AIM:To investigate the effects of laparoscopic hepatectomy for the treatment of hepatocellular carcinoma(HCC) .METHODS:From 2006 to January 2011,laparoscopic hepatectomies were performed on 30 cases of HCC at Northern...AIM:To investigate the effects of laparoscopic hepatectomy for the treatment of hepatocellular carcinoma(HCC) .METHODS:From 2006 to January 2011,laparoscopic hepatectomies were performed on 30 cases of HCC at Northern Jiangsu People's Hospital. During this sametime period,30 patients elected to undergo conventional open hepatectomy over laparoscopic hepatectomy at the time of informed consent. The degree of invasiveness and outcomes of laparoscopic hepatectomy compared to open hepatectomy for HCC were evaluated.RESULTS:Both groups presented with similar bloodloss amounts,operating times and complications. Patients in the laparoscopic hepatectomy group started walking and eating significantly earlier than those inthe open hepatectomy group,and these more rapid recoveries allowed for shorter hospitalizations. There were no significant differences between procedures insurvival rate.CONCLUSION:Laparoscopic hepatectomy is beneficial for patient quality of life if the indications are appropriately based on preoperative liver function and the location and size of the HCC.展开更多
Background Fibroblast growth factor 21 （FGF21） is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduc...Background Fibroblast growth factor 21 （FGF21） is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.Methods The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein （ox-LDL）, and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells （CMECs） were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMFCs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.Results The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 μmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis （P ＜0.05）.Conclusions FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.展开更多
AIM： To explore the anti-inflammatory mechanism of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis induced by acetic acid. METHODS： Spragur-Dawley female rats were divided into four groups： Diammoni...AIM： To explore the anti-inflammatory mechanism of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis induced by acetic acid. METHODS： Spragur-Dawley female rats were divided into four groups： Diammonium Glycyrrhizinate group, dexamethasone group, acetic acid control and normal control group. Colonic inflammation was evaluated by disease activity index, gross morphologic damage, histological injury and colonic myeloperoxidase activity. Immunohistochemistry was used to detect the expression of NF-κB, TNF-α and ICAM-1 in colonic mucosa. RESULTS： Compared to the acetic acid control, both Diammonium Glycyrrhizinate and dexamethasone showed a significant anti-inflammatory effect （P 〈 0.01）. The expression of NF-κB, TNF-α and ICAM-1 in colonic mucosa was significantly lower in the Diammonium Glycyrrhizinate group and dexamethasone group than in the acetic acid group. CONCLUSION： Diammonium Glycyrrhizinate could reduce inflammatory injury in a rat model of ulcerative colitis. This may occur via suppression of NF-κB, TNF-αand ICAM-1 in colonic mucosa.展开更多
Acute-on-chronic liver failure （ACLF） is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The ...Acute-on-chronic liver failure （ACLF） is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells （mDCs） and the efficacy of methylprednisolone （MP） treatment for hepatitis B virus （H BV）-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical （CM） management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.展开更多
Background Acute severe biliary pancreatitis （ASBP） is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects ...Background Acute severe biliary pancreatitis （ASBP） is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects and reduce the expenditure of ASBP treatment.Methods One hundred and five patients diagnosed with ASBP were referred to our department from January 2004 to July 2009. Diagnosis was based on the 2007 criteria of the Chinese Society of Surgery. Patients were divided into two groups; the E group： 50 patients who underwent endoscopic retrograde choledochopancreatography （ERCP） ＋ endoscopic sphincterotomy （EST） ＋ endoscopic lithotripsy basket （ESR） ＋endoscopic retrograde biliary drainage （ERBD）and enteral nutrition （EN）, and the R group： 55 patients who underwent traditional treatment without ERCP. Subsequently,subjective symptoms, signs, biochemical analysis, serum endotoxin, tumor necrosis factor a, grades by computed tomography （CT）, cost of hospitalization and length of stay were compared between the two groups.Results All enrolled patients complied well with all therapeutic regimens. Endoscopic therapy that combined EN could significantly improve symptoms, clinical signs, laboratory values, tumor necrosis factor a and endotoxin while significantly reducing hospital expenditure and length of hospital stay. The experimental findings revealed that there were obvious advantages in the E group compared with the R group.Conclusions Endoscopic therapy combined with EN is an effective, safe and economic therapeutic regimen of ASBP.展开更多
According to geological conditions of No. 3 and No. 4 coal seams （namely A3 and B4） of the Pan＇er coal mine and the parameters of panels 11223, 11224, and 11124 with fully-mechanical coal mining, we built 2D simila...According to geological conditions of No. 3 and No. 4 coal seams （namely A3 and B4） of the Pan＇er coal mine and the parameters of panels 11223, 11224, and 11124 with fully-mechanical coal mining, we built 2D similar material simulation and FLAC3D numerical simulation models to investigate the development of mining-induced stress and the extraction effect of pressure-relief gas with large height and upward mining. Based on a comprehensive analysis of experimental data and observations, we obtained the deformation and breakage characteristics of strata overlying the coal seam, the development patterns of the mining-induced stress and fracture, and the size of the stress-relief area. The stress-relief effect was investigated and analyzed in consideration with mining height and three thick hard strata. Because of the group of three hard thick strata located in the main roof and the residual stress of mined panel 11124, the deformation, breakage, mining-induced stress and fracture development, and the stress-relief coefficient were discontinuous and asymmetrical. The breakage angle of the overlying strata, and the compressive and expansive zones of coal deformation were mainly controlled by the number, thickness, and strength of the hard stratum. Compared with the value of breakage angle derived by the traditional empirical method, the experimental value was lower than the traditional results by 3°-4°below the hard thick strata group, and by 13°-19° above the hard thick strata group. The amount of gas extracted from floor drainage roadway of B4 over 17 months was variable and the amount of gas per month differed considerably, being much smaller when panel 11223 influenced the area of the three hard thick strata. Generally, the stress-relief zone of No. 4 coal seam was small under the influence of the hard thick strata located in the main roof, which played an important role in delaying the breakage time and increasing the breakage space. In this study we gained understanding of the stress-relief mechanism in展开更多
基金supported by the National Science and Technology Major Project of China(2019ZX09732-001)the Key R&D Plan Projects in Shaanxi Province(2020ZDXM2-SF-01)Young Talent fund of the University Association for Science and Technology in Shaanxi,China(20200304).
文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.
文摘Background Shensong Yangxin （SSYX） is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current （/Na）, L-type calcium current （/Ca.L）, transient outward potassium current （/to）, delayed rectifier current （/K）, and inward rectifier potassium currents （/K1） in isolated ventricular myocytes. Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes. Results SSYX decreased peak Na by （44.84±7.65）% from 27.21±5.35 to 14.88±2..75 pA/pF （n=-5, P〈0.05）. The medicine significantly inhibited the /Ca,L. At concentrations of 0.25, 0.50, and 1.00 g/100 ml, the peak/Ca,L was reduced by （19.22±1.10）%, （44.82±6.50）% and （50.69±5.64）%, respectively （n=5, all P〈0.05）. SSYX lifted the I-V curve of both /Na and /Ca,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of /to by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of /K was decreased by （30.77±1.11）% （n=5, P〈0.05） at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of /K was also inhibited. Similar to the effect on /K, the SSYX inhibited /K1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property. Conclusions The experiments revealed that SSYX could block multiple ion channels such as /Na /Ca,L, /k, /to and /K1, which may change the action potential duration and contribute to some of its antiarrhythmic effects.
文摘AIM:To investigate the effects of laparoscopic hepatectomy for the treatment of hepatocellular carcinoma(HCC) .METHODS:From 2006 to January 2011,laparoscopic hepatectomies were performed on 30 cases of HCC at Northern Jiangsu People's Hospital. During this sametime period,30 patients elected to undergo conventional open hepatectomy over laparoscopic hepatectomy at the time of informed consent. The degree of invasiveness and outcomes of laparoscopic hepatectomy compared to open hepatectomy for HCC were evaluated.RESULTS:Both groups presented with similar bloodloss amounts,operating times and complications. Patients in the laparoscopic hepatectomy group started walking and eating significantly earlier than those inthe open hepatectomy group,and these more rapid recoveries allowed for shorter hospitalizations. There were no significant differences between procedures insurvival rate.CONCLUSION:Laparoscopic hepatectomy is beneficial for patient quality of life if the indications are appropriately based on preoperative liver function and the location and size of the HCC.
基金This study was supported by a grant from National Natural Science Foundation of China （No. 81070227）.
文摘Background Fibroblast growth factor 21 （FGF21） is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.Methods The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein （ox-LDL）, and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells （CMECs） were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMFCs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.Results The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 μmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis （P ＜0.05）.Conclusions FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.
基金Supported by the Health Ministry of Shandong Province, No. 2005HW147
文摘AIM： To explore the anti-inflammatory mechanism of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis induced by acetic acid. METHODS： Spragur-Dawley female rats were divided into four groups： Diammonium Glycyrrhizinate group, dexamethasone group, acetic acid control and normal control group. Colonic inflammation was evaluated by disease activity index, gross morphologic damage, histological injury and colonic myeloperoxidase activity. Immunohistochemistry was used to detect the expression of NF-κB, TNF-α and ICAM-1 in colonic mucosa. RESULTS： Compared to the acetic acid control, both Diammonium Glycyrrhizinate and dexamethasone showed a significant anti-inflammatory effect （P 〈 0.01）. The expression of NF-κB, TNF-α and ICAM-1 in colonic mucosa was significantly lower in the Diammonium Glycyrrhizinate group and dexamethasone group than in the acetic acid group. CONCLUSION： Diammonium Glycyrrhizinate could reduce inflammatory injury in a rat model of ulcerative colitis. This may occur via suppression of NF-κB, TNF-αand ICAM-1 in colonic mucosa.
基金ACKNOWLEDGEMENTS This study is supported by the National Natural Science Foundation of China （Nos. 30801039 and 81072424） and the major projects of viral hepatitis from Beijing Municipal Science and Technology Commission （No. H020920020890）. We thank the volunteers who generously participated in this study.
文摘Acute-on-chronic liver failure （ACLF） is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells （mDCs） and the efficacy of methylprednisolone （MP） treatment for hepatitis B virus （H BV）-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical （CM） management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. Furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.
文摘Background Acute severe biliary pancreatitis （ASBP） is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects and reduce the expenditure of ASBP treatment.Methods One hundred and five patients diagnosed with ASBP were referred to our department from January 2004 to July 2009. Diagnosis was based on the 2007 criteria of the Chinese Society of Surgery. Patients were divided into two groups; the E group： 50 patients who underwent endoscopic retrograde choledochopancreatography （ERCP） ＋ endoscopic sphincterotomy （EST） ＋ endoscopic lithotripsy basket （ESR） ＋endoscopic retrograde biliary drainage （ERBD）and enteral nutrition （EN）, and the R group： 55 patients who underwent traditional treatment without ERCP. Subsequently,subjective symptoms, signs, biochemical analysis, serum endotoxin, tumor necrosis factor a, grades by computed tomography （CT）, cost of hospitalization and length of stay were compared between the two groups.Results All enrolled patients complied well with all therapeutic regimens. Endoscopic therapy that combined EN could significantly improve symptoms, clinical signs, laboratory values, tumor necrosis factor a and endotoxin while significantly reducing hospital expenditure and length of hospital stay. The experimental findings revealed that there were obvious advantages in the E group compared with the R group.Conclusions Endoscopic therapy combined with EN is an effective, safe and economic therapeutic regimen of ASBP.
基金Acknowledgments This work is supported by the National Nature Science Foundation of China （51374011）.
文摘According to geological conditions of No. 3 and No. 4 coal seams （namely A3 and B4） of the Pan＇er coal mine and the parameters of panels 11223, 11224, and 11124 with fully-mechanical coal mining, we built 2D similar material simulation and FLAC3D numerical simulation models to investigate the development of mining-induced stress and the extraction effect of pressure-relief gas with large height and upward mining. Based on a comprehensive analysis of experimental data and observations, we obtained the deformation and breakage characteristics of strata overlying the coal seam, the development patterns of the mining-induced stress and fracture, and the size of the stress-relief area. The stress-relief effect was investigated and analyzed in consideration with mining height and three thick hard strata. Because of the group of three hard thick strata located in the main roof and the residual stress of mined panel 11124, the deformation, breakage, mining-induced stress and fracture development, and the stress-relief coefficient were discontinuous and asymmetrical. The breakage angle of the overlying strata, and the compressive and expansive zones of coal deformation were mainly controlled by the number, thickness, and strength of the hard stratum. Compared with the value of breakage angle derived by the traditional empirical method, the experimental value was lower than the traditional results by 3°-4°below the hard thick strata group, and by 13°-19° above the hard thick strata group. The amount of gas extracted from floor drainage roadway of B4 over 17 months was variable and the amount of gas per month differed considerably, being much smaller when panel 11223 influenced the area of the three hard thick strata. Generally, the stress-relief zone of No. 4 coal seam was small under the influence of the hard thick strata located in the main roof, which played an important role in delaying the breakage time and increasing the breakage space. In this study we gained understanding of the stress-relief mechanism in
