AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK...AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis B.METHODS:We designed the study as a randomized controlled clinical trial.Registration number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study.Participants were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine treatment.All participants were treated for 8 wk and then followed at 48 wk following their final treatment.The primaryefficacy end point was the patient fatality rate in each group.Measurements of various virological and biochemical indicators served as secondary endpoints.The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P<0.05).However,there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups(P>0.05).Patients in the"TTK"group had significantly higher levels of serum total bilirubin compared to MMC subjects(339.40μm展开更多
Although the liver has a high regenerative capacity,as a result of massive hepatocyte death,liver failure occurs. In addition to liver failure,for acute,chronic and hereditary diseases of the liver,cell transplantatio...Although the liver has a high regenerative capacity,as a result of massive hepatocyte death,liver failure occurs. In addition to liver failure,for acute,chronic and hereditary diseases of the liver,cell transplantation therapies can stimulate regeneration or at least ensure sufficient function until liver transplantation can be performed. The lack of donor organs and the risks of rejection have prompted extensive experimental and clinical research in the field of cellular transplantation. Transplantation of cell lineages involved in liver regeneration,including mature hepatocytes,fetal hepatocytes,fetal liver progenitor cells,fetal stem cells,hepatic progenitor cells,hepatic stem cells,mesenchymal stem cells,hematopoietic stem cells,and peripheral blood and umbilical cord blood stem cells,have been found to be beneficial in the treatment of liver failure.In this article,the results of experimental and clinical cell transplantation trials for liver failure are reviewed,with an emphasis on regeneration.展开更多
BACKGROUND: Augmenter of liver regeneration (ALR) is an important polypeptide in the process of liver regeneration. This study aimed to determine the expression level of ALR in different liver diseases and its signifi...BACKGROUND: Augmenter of liver regeneration (ALR) is an important polypeptide in the process of liver regeneration. This study aimed to determine the expression level of ALR in different liver diseases and its significance. METHODS: We prepared murine polyclonal antibody against ALR protein from Balb/C mice and purified the IgG fraction, which specifically combined to ALR protein as shown by Western blotting. Serum ALR levels in patients with hepatocellular carcinoma (HCC), hepatic failure (HF), chronic hepatitis B, and healthy persons were compared by ELISA. ALR mRNA expression levels in liver tissues in some of these patients were also compared by real-time RT-PCR. Immunohistochemical analysis was carried out on HF and HCC liver tissues. RESULTS: Different serum ALR levels foreshowed completely different prognoses in 18 HF patients. Higher ALR levels were noted in 6 improved patients (1613.5+/-369.6 pmol/ml) than in 12 deteriorating patients (462.3+/-235.8 pmol/m1). Similar levels were found in 20 HCC patients (917.9+/-332. 7 pmol/m1), 24 chronic hepatitis B patients (969.2+/-332.5 pmol/ml) and 10 healthy persons (806.9+/-240.8 pmol/ml). ALR mRNA levels in HCC liver tissues [10E6.24 (1.74x10(6)) copies/mu l] were much higher than in those of HF patients receiving orthotopic liver transplantation [10E3.45 (2.82x10(3)) copies/mu l] or in healthy liver tissues [10E4.31 (2.04x10(4)) copies/mu l]. In immunohistochemical analysis, positive immunostaining in HCC liver tissue was more intense than that in HF liver tissue. CONCLUSION: Serum ALR level is helpful in estimating the survival time of patients with HF, and ALR may play an important role in hepatocarcinogenesis.展开更多
Myoblast implantation is a unique, patented technology of muscle regeneration being tested in Phase III clinical trials of muscular dystrophy, ischemic cardiomyopathy, Phase II trial of cancer, and Phase I trial of Ty...Myoblast implantation is a unique, patented technology of muscle regeneration being tested in Phase III clinical trials of muscular dystrophy, ischemic cardiomyopathy, Phase II trial of cancer, and Phase I trial of Type II diabetes. Differentiated and committed, myoblasts are not stem cells. Implanted myoblasts fuse spontaneously among themselves, replenishing genetically normal myofibers. They also fuse with genetically abnormal myofibers of muscular dystrophy, cardiomyopathy, or Type II diabetes, transferring their nuclei containing the normal human genome to provide stable, long-term expression of the missing gene products. They develop to become cardiomyocytes in the infracted myocardium. Myoblasts transduced with VEGF<sub>165</sub> allow concomitant regeneration of blood capillaries and myofibers. They are potent biologics for treating heart failure, ischemic cardiomyopathy, diabetic ischemia, erectile dysfunction, and baldness. Myoblasts, because of their small size, spindle shape, and resilience, can grow within wrinkles and on skin surfaces, thus enhancing the color, luster and texture of the skin “plated” with them. They can be injected subcutaneously as a cellular filler to reduce wrinkles. Intramuscular injection of myoblasts can augment the size, shape, consistency, tone and strength of muscle groups, improving the lines, contours and vitality to sculpt a youthful appearance. This highly promising technology has great social economic values in treating hereditary, fatal and debilitating disease conditions.展开更多
BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of t...BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically significant.CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.展开更多
The liver is an extraordinary organ known for its remarkable regenerative capacity(1).This regenerative ability lays the foundation for various therapeutic approaches,such as partial hepatectomy(PHx),split-liver trans...The liver is an extraordinary organ known for its remarkable regenerative capacity(1).This regenerative ability lays the foundation for various therapeutic approaches,such as partial hepatectomy(PHx),split-liver transplantation,live-donor liver transplantation,and associated liver partition and portal vein ligation for staged hepatectomy(ALPPS).展开更多
This paper discusses the control strategy for energy management in railway transit network with wayside(substation)supercapacitor(SC)energy storage system(ESS).Firstly,the structure of the wayside energy storage syste...This paper discusses the control strategy for energy management in railway transit network with wayside(substation)supercapacitor(SC)energy storage system(ESS).Firstly,the structure of the wayside energy storage system is introduced.Secondly,the model of energy storage system is built and the control strategy is described.Thirdly,in order to estimate the required energy storage system,a useful method is proposed to predict the instantaneous regenerative energy magnitude which is delivered to each substation.Finally,the ESS configuration for each substation is determined.A simplified mathematical model of the whole metro network is established and the main features of the control strategy are developed.Numerical simulations show the efficacy of suggested control strategy and the energy saving obtained for railway transit network.展开更多
Although substantial advances have been made in treating ischemic heart disease and subsequent heart failure, the overall morbidity and mortality from these conditions remain high. Stem cell-based therapy has emerged ...Although substantial advances have been made in treating ischemic heart disease and subsequent heart failure, the overall morbidity and mortality from these conditions remain high. Stem cell-based therapy has emerged as a promising approach for prompting cardiac rejuvenation. Various cell types have been tested in the clinical arena, proving consistent safety results. As for efficiency outcomes, contradictory findings have been reported, partly due to inconsistency in study protocols but also due to poor survival, engraftment and differentiation of transplanted cells in the hostile milieu of the ischemic host tissue. Studies have varied in terms of route of delivery, type and dose of implanted stem cells, patient selection and randomization, and assessment of therapeutic effect. Founded on the main achievements and challenges within almost 20 years of research, a number of official documents have been published by leading experts in the field. Core recommendations have focused on developing and optimizing effective strategies to enrich cell retention and their regenerative potential. Issued consensus and position papers have stemmed from an unmet need to provide a harmonized framework for future research, resulting in improved therapeutic application of cell-based therapies for cardiac regeneration and repair.展开更多
基金Supported by National Science and Technology Key Projects on"Major Infectious Diseases such as HIV/AIDS,Viral Hepatitis Prevention and Treatment",No.2008ZX10005-007Research Projects of Key Disease of National Traditional Chinese Medicine(Hepatopathy)Clinical Research Center(Hubei Province),No.JDZX2012054+3 种基金National Natural Science Foundation of China,No.81373513,No.90709041,No.30672590,No.30271562,No.30371787,No.81102531 and No.81274147Key Projects of Natural Science Foundation of Hubei Province,No.2011CDB463Specialized Research Fund for the Doctoral Programs in Institution of Higher Education,No.20124230110001Key Subjects of Department of Science and Technology of Wuhan City,No.201260523199
文摘AIM:To study the clinical efficacy of traditional Chinese medicine(TCM)intervention"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")for treating liver failure due to chronic hepatitis B.METHODS:We designed the study as a randomized controlled clinical trial.Registration number of Chinese Clinical Trial Registry is Chi CTR-TRC-12002961.A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study.Participants were randomly assigned to the following three groups:(1)a modern medicine control group(MMC group,36patients);(2)a"tonifying qi and detoxification"("TQD")group(72 patients);and(3)a"tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment"("TTK")group(36patients).Patients in the MMC group received general internal medicine treatment;patients in the"TQD"group were given a TCM formula"tonifying qi and detoxification"and general internal medicine treatment;patients in the"TTK"group were given a TCM formula of"TTK"and general internal medicine treatment.All participants were treated for 8 wk and then followed at 48 wk following their final treatment.The primaryefficacy end point was the patient fatality rate in each group.Measurements of various virological and biochemical indicators served as secondary endpoints.The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups.RESULTS:At the 48-wk post-treatment time point,the patient fatality rates in the MMC,"TQD",and"TTK"groups were 51.61%,35.38%,and 16.67%,respectively,and the differences between groups were statistically significant(P<0.05).However,there were no significant differences in the levels of hepatitis B virus DNA or prothrombin activity among the three groups(P>0.05).Patients in the"TTK"group had significantly higher levels of serum total bilirubin compared to MMC subjects(339.40μm
文摘Although the liver has a high regenerative capacity,as a result of massive hepatocyte death,liver failure occurs. In addition to liver failure,for acute,chronic and hereditary diseases of the liver,cell transplantation therapies can stimulate regeneration or at least ensure sufficient function until liver transplantation can be performed. The lack of donor organs and the risks of rejection have prompted extensive experimental and clinical research in the field of cellular transplantation. Transplantation of cell lineages involved in liver regeneration,including mature hepatocytes,fetal hepatocytes,fetal liver progenitor cells,fetal stem cells,hepatic progenitor cells,hepatic stem cells,mesenchymal stem cells,hematopoietic stem cells,and peripheral blood and umbilical cord blood stem cells,have been found to be beneficial in the treatment of liver failure.In this article,the results of experimental and clinical cell transplantation trials for liver failure are reviewed,with an emphasis on regeneration.
基金supported by grants from the National Natural Science Foundation of China (30972592 and 30970747)Zhejiang Provincial Natural Science Foundation (Y2090010)
文摘BACKGROUND: Augmenter of liver regeneration (ALR) is an important polypeptide in the process of liver regeneration. This study aimed to determine the expression level of ALR in different liver diseases and its significance. METHODS: We prepared murine polyclonal antibody against ALR protein from Balb/C mice and purified the IgG fraction, which specifically combined to ALR protein as shown by Western blotting. Serum ALR levels in patients with hepatocellular carcinoma (HCC), hepatic failure (HF), chronic hepatitis B, and healthy persons were compared by ELISA. ALR mRNA expression levels in liver tissues in some of these patients were also compared by real-time RT-PCR. Immunohistochemical analysis was carried out on HF and HCC liver tissues. RESULTS: Different serum ALR levels foreshowed completely different prognoses in 18 HF patients. Higher ALR levels were noted in 6 improved patients (1613.5+/-369.6 pmol/ml) than in 12 deteriorating patients (462.3+/-235.8 pmol/m1). Similar levels were found in 20 HCC patients (917.9+/-332. 7 pmol/m1), 24 chronic hepatitis B patients (969.2+/-332.5 pmol/ml) and 10 healthy persons (806.9+/-240.8 pmol/ml). ALR mRNA levels in HCC liver tissues [10E6.24 (1.74x10(6)) copies/mu l] were much higher than in those of HF patients receiving orthotopic liver transplantation [10E3.45 (2.82x10(3)) copies/mu l] or in healthy liver tissues [10E4.31 (2.04x10(4)) copies/mu l]. In immunohistochemical analysis, positive immunostaining in HCC liver tissue was more intense than that in HF liver tissue. CONCLUSION: Serum ALR level is helpful in estimating the survival time of patients with HF, and ALR may play an important role in hepatocarcinogenesis.
文摘Myoblast implantation is a unique, patented technology of muscle regeneration being tested in Phase III clinical trials of muscular dystrophy, ischemic cardiomyopathy, Phase II trial of cancer, and Phase I trial of Type II diabetes. Differentiated and committed, myoblasts are not stem cells. Implanted myoblasts fuse spontaneously among themselves, replenishing genetically normal myofibers. They also fuse with genetically abnormal myofibers of muscular dystrophy, cardiomyopathy, or Type II diabetes, transferring their nuclei containing the normal human genome to provide stable, long-term expression of the missing gene products. They develop to become cardiomyocytes in the infracted myocardium. Myoblasts transduced with VEGF<sub>165</sub> allow concomitant regeneration of blood capillaries and myofibers. They are potent biologics for treating heart failure, ischemic cardiomyopathy, diabetic ischemia, erectile dysfunction, and baldness. Myoblasts, because of their small size, spindle shape, and resilience, can grow within wrinkles and on skin surfaces, thus enhancing the color, luster and texture of the skin “plated” with them. They can be injected subcutaneously as a cellular filler to reduce wrinkles. Intramuscular injection of myoblasts can augment the size, shape, consistency, tone and strength of muscle groups, improving the lines, contours and vitality to sculpt a youthful appearance. This highly promising technology has great social economic values in treating hereditary, fatal and debilitating disease conditions.
文摘BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and 7.RESULTS: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically significant.CONCLUSIONS: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of liver regeneration.
文摘The liver is an extraordinary organ known for its remarkable regenerative capacity(1).This regenerative ability lays the foundation for various therapeutic approaches,such as partial hepatectomy(PHx),split-liver transplantation,live-donor liver transplantation,and associated liver partition and portal vein ligation for staged hepatectomy(ALPPS).
文摘This paper discusses the control strategy for energy management in railway transit network with wayside(substation)supercapacitor(SC)energy storage system(ESS).Firstly,the structure of the wayside energy storage system is introduced.Secondly,the model of energy storage system is built and the control strategy is described.Thirdly,in order to estimate the required energy storage system,a useful method is proposed to predict the instantaneous regenerative energy magnitude which is delivered to each substation.Finally,the ESS configuration for each substation is determined.A simplified mathematical model of the whole metro network is established and the main features of the control strategy are developed.Numerical simulations show the efficacy of suggested control strategy and the energy saving obtained for railway transit network.
文摘Although substantial advances have been made in treating ischemic heart disease and subsequent heart failure, the overall morbidity and mortality from these conditions remain high. Stem cell-based therapy has emerged as a promising approach for prompting cardiac rejuvenation. Various cell types have been tested in the clinical arena, proving consistent safety results. As for efficiency outcomes, contradictory findings have been reported, partly due to inconsistency in study protocols but also due to poor survival, engraftment and differentiation of transplanted cells in the hostile milieu of the ischemic host tissue. Studies have varied in terms of route of delivery, type and dose of implanted stem cells, patient selection and randomization, and assessment of therapeutic effect. Founded on the main achievements and challenges within almost 20 years of research, a number of official documents have been published by leading experts in the field. Core recommendations have focused on developing and optimizing effective strategies to enrich cell retention and their regenerative potential. Issued consensus and position papers have stemmed from an unmet need to provide a harmonized framework for future research, resulting in improved therapeutic application of cell-based therapies for cardiac regeneration and repair.
