BACKGROUND： In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS： From July 2011 to August 2012, our ...BACKGROUND： In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS： From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively.RESULTS： Among the 29 donors, 24 were China Category II donors（organ donation after cardiac death）, and five were China Category III donors（organ donation after brain death followed by cardiac death）. The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422（2-696） days. Among the five mortalities during the follow-up,three died of tumor recurrence. In terms of post-transplant complications, 9 recipients（34.6%） experienced early allograft dysfunction, 1（3.8%） had non-anastomotic biliary stricture,and 1（3.8%） was complicated with hepatic arterial thrombosis.None of these complications resulted in patient death. Notably,primary non-function was not observed in any of the grafts.CONCLUSION： With careful donor selection, liver transplant from deceased donors can be performed safely and plays acritical role in overcoming the extreme organ shortage in China.展开更多
The worldwide interest in the gut microbiome and its impact on the upstream liver highlight a critical upside to breath research: it can uniquely measure otherwise unmeasurable biology. Bacteria make gases [volatile o...The worldwide interest in the gut microbiome and its impact on the upstream liver highlight a critical upside to breath research: it can uniquely measure otherwise unmeasurable biology. Bacteria make gases [volatile organic compounds(VOCs)] that are directly relevant to pathophysiology of the fatty liver and associated conditions, including obesity. Measurement of these VOCs and their metabolites in the exhaled breath, therefore, present an opportunity to safely and easily evaluate, on both a personal and a population level, some of our most pressing public health threats. This is an opportunity that must be pursued. To date, however, breath analysis remains a slowly evolving field which only occasionally impacts clinical research or patient care. One major obstacle to progress is that breath analysis is inherently and emphatically mutli-disciplinary: it connects engineering, chemistry, breath mechanics, biology and medicine. Unbalanced or incomplete teams may produce inconsistent and often unsatisfactory results. A second impediment is the lack of a well-known stepwise structure for the development of non-invasive diagnostics. As a result, the breath research landscape is replete with orphaned single-center pilot studies. Often, important hypotheses and key observations have not been pursued to maturation. This paper reviews the rationale and requirements for breath VOC research applied to the gut-fatty liver axis and offers some suggestions for future development.展开更多
Organic anion transporters(OATs)and organic anion transporter polypeptides(OATPs)are classified within two SLC superfamilies,namely,the SLC22A superfamily and the SLCO superfamily(formerly the SLC21A family),respectiv...Organic anion transporters(OATs)and organic anion transporter polypeptides(OATPs)are classified within two SLC superfamilies,namely,the SLC22A superfamily and the SLCO superfamily(formerly the SLC21A family),respectively.They are expressed in many tissues,such as the liver and kidney,and mediate the absorption and excretion of many endogenous and exogenous substances,including various drugs.Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm.OATs and OATPs are abundantly expressed in the liver,where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs.However,differences in the locations of glycosylation sites,phosphorylation sites,and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver,which ultimately results in their different roles in the liver.To date,few articles have addressed these aspects of OAT and OATP structures,and we study further the similarities and differences in their structures,tissue distribution,substrates,and roles in liver diseases.展开更多
Radiation for targeting liver tumors can be challenging because of the damage that it can cause to sensitive organs such as heart and kidney.To calculate the dose received by noninvolved organs,a modeling of the pati...Radiation for targeting liver tumors can be challenging because of the damage that it can cause to sensitive organs such as heart and kidney.To calculate the dose received by noninvolved organs,a modeling of the patient’s entire body is necessary.Therefore,in this study,a human Oak Ridge National Laboratory-Medical Internal Radiation Dose phantom was used for liver proton therapy simulation.The results show that the optimum proton energy interval covering the whole tumor was in the range of 90-120 MeV.A spread-out Bragg peak was built by adding Bragg peaks to cover the liver tumor volume,and beam parameters recommended by the International Commission on Radiation Units and Measurements(ICRU) were evaluated.The flux of secondary particles was calculated on the surface of the tumor,and two-dimensional dose distributions for protons,neutrons and photons were shown.Finally,the total doses of protons,photons and neutrons in tumor and 14 noninvolved organs were calculated.The results indicated that the ratio of received dose to the normal tissue of the liver concerning the spherical tumor of 2 cm in radius was approximately0.01.This ratio for organs such as gall bladder,heart and kidney was approximately 8.4×10-5,5.1×10-5 and2.34×10-5.Secondary particles such as neutrons andphotons deposit their energies to organs located far from the treatment volume,thus increasing the risk of secondary cancers.The research results indicated that the secondary particles dose was quite small in liver proton therapy.All the calculations were performed using Monte Carlo N-Particle Transport Code (MCNP).展开更多
Objective To summarize our clinical experience in liver transplantation while considering the background in this filed in China. Methods Ninety-five patients who had received liver transplantation from April 1993 to M...Objective To summarize our clinical experience in liver transplantation while considering the background in this filed in China. Methods Ninety-five patients who had received liver transplantation from April 1993 to March 2002 were analyzed retrospectively. Three periods were defined objectively as period Ⅰ(1993-1997),Ⅱ(1999) and Ⅲ(2000 -2002). Operative techniques, recipients, original diseases, complications and survival rates were compared among the three periods. Results Malignant liver lesions were the main cause for liver transplantation in period Ⅰ and Ⅱ. The ratio of number of malignant disease to total recipients decreased gradually from period Ⅰ to Ⅱ (100%, 53% and 35%, respectively). The 1-year survival rate in patients with benign liver disease was 85 % and the total operative mortality was 5% in period Ⅲ. The incidence of hepatitis B virus reactivation or reinfection was 24% twelve months after liver transplantation. Vascular complication decreased but biliary complications did展开更多
Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolyt...Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.展开更多
基金supported by grants from the National High Technology Research and Development Program of China(863 Program)(2012AA021008)the Special Fund for Science Research by Ministry of Health(201302009)
文摘BACKGROUND： In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS： From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively.RESULTS： Among the 29 donors, 24 were China Category II donors（organ donation after cardiac death）, and five were China Category III donors（organ donation after brain death followed by cardiac death）. The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422（2-696） days. Among the five mortalities during the follow-up,three died of tumor recurrence. In terms of post-transplant complications, 9 recipients（34.6%） experienced early allograft dysfunction, 1（3.8%） had non-anastomotic biliary stricture,and 1（3.8%） was complicated with hepatic arterial thrombosis.None of these complications resulted in patient death. Notably,primary non-function was not observed in any of the grafts.CONCLUSION： With careful donor selection, liver transplant from deceased donors can be performed safely and plays acritical role in overcoming the extreme organ shortage in China.
文摘The worldwide interest in the gut microbiome and its impact on the upstream liver highlight a critical upside to breath research: it can uniquely measure otherwise unmeasurable biology. Bacteria make gases [volatile organic compounds(VOCs)] that are directly relevant to pathophysiology of the fatty liver and associated conditions, including obesity. Measurement of these VOCs and their metabolites in the exhaled breath, therefore, present an opportunity to safely and easily evaluate, on both a personal and a population level, some of our most pressing public health threats. This is an opportunity that must be pursued. To date, however, breath analysis remains a slowly evolving field which only occasionally impacts clinical research or patient care. One major obstacle to progress is that breath analysis is inherently and emphatically mutli-disciplinary: it connects engineering, chemistry, breath mechanics, biology and medicine. Unbalanced or incomplete teams may produce inconsistent and often unsatisfactory results. A second impediment is the lack of a well-known stepwise structure for the development of non-invasive diagnostics. As a result, the breath research landscape is replete with orphaned single-center pilot studies. Often, important hypotheses and key observations have not been pursued to maturation. This paper reviews the rationale and requirements for breath VOC research applied to the gut-fatty liver axis and offers some suggestions for future development.
文摘Organic anion transporters(OATs)and organic anion transporter polypeptides(OATPs)are classified within two SLC superfamilies,namely,the SLC22A superfamily and the SLCO superfamily(formerly the SLC21A family),respectively.They are expressed in many tissues,such as the liver and kidney,and mediate the absorption and excretion of many endogenous and exogenous substances,including various drugs.Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm.OATs and OATPs are abundantly expressed in the liver,where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs.However,differences in the locations of glycosylation sites,phosphorylation sites,and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver,which ultimately results in their different roles in the liver.To date,few articles have addressed these aspects of OAT and OATP structures,and we study further the similarities and differences in their structures,tissue distribution,substrates,and roles in liver diseases.
文摘Radiation for targeting liver tumors can be challenging because of the damage that it can cause to sensitive organs such as heart and kidney.To calculate the dose received by noninvolved organs,a modeling of the patient’s entire body is necessary.Therefore,in this study,a human Oak Ridge National Laboratory-Medical Internal Radiation Dose phantom was used for liver proton therapy simulation.The results show that the optimum proton energy interval covering the whole tumor was in the range of 90-120 MeV.A spread-out Bragg peak was built by adding Bragg peaks to cover the liver tumor volume,and beam parameters recommended by the International Commission on Radiation Units and Measurements(ICRU) were evaluated.The flux of secondary particles was calculated on the surface of the tumor,and two-dimensional dose distributions for protons,neutrons and photons were shown.Finally,the total doses of protons,photons and neutrons in tumor and 14 noninvolved organs were calculated.The results indicated that the ratio of received dose to the normal tissue of the liver concerning the spherical tumor of 2 cm in radius was approximately0.01.This ratio for organs such as gall bladder,heart and kidney was approximately 8.4×10-5,5.1×10-5 and2.34×10-5.Secondary particles such as neutrons andphotons deposit their energies to organs located far from the treatment volume,thus increasing the risk of secondary cancers.The research results indicated that the secondary particles dose was quite small in liver proton therapy.All the calculations were performed using Monte Carlo N-Particle Transport Code (MCNP).
文摘Objective To summarize our clinical experience in liver transplantation while considering the background in this filed in China. Methods Ninety-five patients who had received liver transplantation from April 1993 to March 2002 were analyzed retrospectively. Three periods were defined objectively as period Ⅰ(1993-1997),Ⅱ(1999) and Ⅲ(2000 -2002). Operative techniques, recipients, original diseases, complications and survival rates were compared among the three periods. Results Malignant liver lesions were the main cause for liver transplantation in period Ⅰ and Ⅱ. The ratio of number of malignant disease to total recipients decreased gradually from period Ⅰ to Ⅱ (100%, 53% and 35%, respectively). The 1-year survival rate in patients with benign liver disease was 85 % and the total operative mortality was 5% in period Ⅲ. The incidence of hepatitis B virus reactivation or reinfection was 24% twelve months after liver transplantation. Vascular complication decreased but biliary complications did
文摘Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.
