A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography.She had taken oral contraceptives for only one month at the age of thirty.Physical examination revealed no abnor...A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography.She had taken oral contraceptives for only one month at the age of thirty.Physical examination revealed no abnormalities,and laboratory data,including hepatic function tests,were within the normal range,with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-Ⅱ (3 502 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass measuring 10×10 cm in the left posterior segment of the liver.Because hepatocellular carcinoma could not be completely excluded,this mass was resected.The tumor consisted of sheets of uniform cells with clear cytoplasm, perinuclear eosinophilic granules and round nuclei.These histological findings were consistent with liver cell adenoma. Background hepatic tissue appeared normal.After resection of the tumor,serum PIVKA-Ⅱ fell to within the normal range. An area of hepatocellular carcinoma (HCC) with a mid- trabecular pattern was immunohistochemically found,which was positive for PIVKA-Ⅱ.Sinusoidal endothelial cells were CD34-positive,containing scattered PIVKA-Ⅱ positive cells. This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.展开更多
We report a case of liver cell adenoma （LCA） in a 33-year-old female patient with special respect to its clonality status, pathogenic factors and differential diagnosis. The case was examined by histopathology, immu...We report a case of liver cell adenoma （LCA） in a 33-year-old female patient with special respect to its clonality status, pathogenic factors and differential diagnosis. The case was examined by histopathology, immunohistochemistry and a clonality assay based on X-chromosomal inactivation mosaicism in female somatic tissues and polymorphism at androgen receptor focus. The clinicopathological features of the reported cases from China and other countries were compared. The lesion was spherical, sizing 2 cm in its maximal dimension. Histologically, it was composed of cells arranged in cords, most of which were two-cell-thick and separated by sinusoids. Focal fatty change and excessive glycogen storage were observed. The tumor cells were round or polygonal in shape, resembling the surrounding parenchymal cells. Mitosis was not found. No portal tract, central vein or ductule was found within the lesion. The tumor tissue showed a positive reaction for cytokeratin （CK） 18, but not for CK19, vimentin, estrogen and progesterone receptors. Monoclonality was demonstrated for the lesion, confirming the diagnosis of an LCA. Clonality analysis is helpful for its distinction from focal nodular hyperplasia.K展开更多
A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives.Radiological diagnostics showed the typical findings of liver cell a...A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives.Radiological diagnostics showed the typical findings of liver cell adenoma(LCA).Dynamic computed tomography revealed that the tumor showed a homogenous enhancement in the arterial phase and almost the same enhancement as the surrounding liver parenchyma in the delayed phase.The tumor was found to contain fat on magnetic resonance imaging.A benign fat containing liver tumor was suggested.However,radiological findings altered,which caused us to suspect that a welldifferentiated hepatocellular carcinoma(HCC)containing fat was becoming dedifferentiated.Partial hepatectomy was performed and the pathological findings showed the typical findings of LCA.This case was an extremely rare LCA,which had no background of risk for LCA and developed the sequential alteration of the radiological findings to suspect well-differentiated HCC.展开更多
AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into ...AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.展开更多
BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these ...BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. METHODS: A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+ IL-17+ cells were measured by flow cytometry The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes Percentages of circulating Th17 cells were compared between the two groups and controls. RESULTS: The levels of circulating CD4+ IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56±0.43% versus 1.79±0.44% P<0.001). The frequency of CD4+ IL-17+ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002).CONCLUSION: Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.展开更多
Objective:To study the correlation of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 expression with the illness in patients with chronic hepatitis b (CHB).Methods: A total of 48 patients who were diagnosed w...Objective:To study the correlation of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 expression with the illness in patients with chronic hepatitis b (CHB).Methods: A total of 48 patients who were diagnosed with chronic hepatitis b in Jianyang People's Hospital between July 2014 and January 2017 were selected as the CHB group of the research, 66 healthy volunteers who received physical examination during the same period were selected as control group, the peripheral blood was collected to determine Th17 cell surface CCR4, CCR6 and CXCR3 expression, and serum was collected to determine the levels of Th17 cytokines, liver function indexes and liver fibrosis indexes.Results: Peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity of CHB group were significantly higher than those of control group;serum IL-17, IL-21, IL-22, ALT, AST, GLB, HA, PC-Ⅲ, LN and C-Ⅳ levels of CHB group were significantly higher than those of control group and positively correlated with peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity while serum ALB level was significantly lower than that of control group and negatively correlated with peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity.Conclusion: The high expression of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 in patients with CHB can result in increased secretion of Th17 cytokines, liver function injury and liver fibrosis.展开更多
We report the first case of a healthy 23-year-old female who underwent an interventional radiology-guided embolization of a hepatic adenoma, which resulted in a gas forming hepatic liver abscess and septicemia by Clos...We report the first case of a healthy 23-year-old female who underwent an interventional radiology-guided embolization of a hepatic adenoma, which resulted in a gas forming hepatic liver abscess and septicemia by Clostridium paraputrificum. A retrospective review of Clostridial liver abscesses was performed using a Pub Med literature search, and we found 57 clostridial hepatic abscess cases. The two most commonly reported clostridial species are C. perfringens and C. septicum(64.9% and 17.5% respectively). C. perfringens cases carried a mortality of 67.6% with median survival of 11 h, and 70.2% of the C. perfringens cases experienced hemolysis. All C. septicum cases were found to have underlying liver malignancy at the time of the presentation with a mortality of only 30%. The remaining cases were caused by various Clostridium species, and this cohort's clinical course was significantly milder when compared to the above C. perfringens and C. septicum cohorts.展开更多
目的探讨不同病因所致肝衰竭患者外周血单个核细胞(PBMCs)HLA-DR m RNA及Th17和CD4^+CD25^+Treg细胞水平的变化及其意义。方法本研究纳入肝衰竭患者50例,其中乙型肝炎肝衰竭15例,药物性肝损伤12例,酒精性肝病13例,自身免疫性肝炎10例;...目的探讨不同病因所致肝衰竭患者外周血单个核细胞(PBMCs)HLA-DR m RNA及Th17和CD4^+CD25^+Treg细胞水平的变化及其意义。方法本研究纳入肝衰竭患者50例,其中乙型肝炎肝衰竭15例,药物性肝损伤12例,酒精性肝病13例,自身免疫性肝炎10例;慢性乙型肝炎患者17例和正常人10例。采用PCR法检测PBMCs中HLA-DR m RNA水平,使用流式细胞仪检测CD4^+CD25^+Treg和Th17细胞百分比。结果乙型肝炎肝衰竭患者HLA-DR m RNA水平为(134.5±15.2),显著高于药物性肝损伤组的(17.9±1.2)、酒精性肝病组的(19.6±2.0)和自身免疫性肝炎组的[(11.2±1.2),P<0.05];不同病因肝衰竭患者Th17和CD4^+CD25^+Treg细胞百分比[分别为(4.4±0.6)%和(3.9±0.6)%左右]的差异无统计学意义(P>0.05),但与慢性乙型肝炎[分别为(3.7±0.2)%和(6.1±0.4)%和正常人(2.1±0.7)%和(7.0±0.9)%比,均有显著性差异(P<0.05);对不同病因肝衰竭患者进行动态观察发现,19例死亡患者CD4^+CD25^+Treg细胞百分比呈持续下降,直至死亡,而31例生存患者则逐渐恢复至接近正常水平。结论外周血单个核细胞HLA-DR m RNA水平及Th17和CD4^+CD25^+Treg细胞百分比的变化与肝衰竭患者的病情密切相关,可作为判断肝衰竭严重程度及预后的指标。展开更多
Recently,the Th17 cells and IL-17 have been shown to play a critical role in the immune-mediated liver injury in hepatitis B,while their functions in acute liver failure have not been well elucidated yet.In this study...Recently,the Th17 cells and IL-17 have been shown to play a critical role in the immune-mediated liver injury in hepatitis B,while their functions in acute liver failure have not been well elucidated yet.In this study,we primarily investigated the role of IL-17 in the development of mouse hepatitis virus strain 3(MHV-3)-induced acute liver failure.IL-17 mRNA levels in liver tissue were quantified by using quantitative real-time polymerase chain reaction,and cytokine IL-17 levels in liver tissue and serum were determined by using ELISA in MHV-3-induced murine fulminant hepatitis model.The IL-17 expression levels on CD4 + T and CD8 + T cells were determined by using flow cytometry.The correlation between IL-17 level and liver injury was studied.Th17 associated cytokines were also investigated by intracellular staining.Our results showed that the IL-17 expression was significantly elevated in the liver and serum of BALB/cJ mice infected with MHV-3.Moreover,a time course study showed that the percentage of both IL-17-producing CD4 + T cells and IL-17-producing CD8 + T cells was increased remarkably in the liver starting from 48 h and peaked at 72 h post-infection.There was a close correlation between hepatic or serum IL-17 concentration and the severity of liver injury defined by ALT level,respectively.Th17 associated cytokines,IL-6,IL-21 and IL-22,were also increased significantly at 72 h post-infection.It was concluded that IL-17 may contribute to the pathogenesis of MHV-3-induced acute liver failure.展开更多
Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the n...Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the neonatal period.Regulatory T cells(Tregs)are essential for maintaining immune tolerance/homeostasis and modulating inflammatory responses.The features of Tregs in the neonatal liver under steady-state conditions are not well understood.The present study aimed to investigate the phenotype,functions,and significance of neonatal Tregs in the liver.We found a wave of thymus-derived Treg influx into the liver during 1–2 weeks of age.Depletion of these Tregs between days 7 and 11 after birth rapidly resulted in Th1-type liver inflammation and metabolic disorder.More Tregs in the neonatal liver than in the spleen underwent MHC II-dependent activation and proliferation,and the liver Tregs acquired stronger suppressive functions.The transcriptomic profile of these neonatal liver Tregs showed elevated expression of PPARγand T-bet and features of Tregs that utilize lipid metabolic machinery and are capable of regulating Th1 responses.The accumulation of Tregs with unique features in the neonatal liver is critical to ensure self-tolerance and liver maturation.展开更多
文摘A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography.She had taken oral contraceptives for only one month at the age of thirty.Physical examination revealed no abnormalities,and laboratory data,including hepatic function tests,were within the normal range,with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-Ⅱ (3 502 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass measuring 10×10 cm in the left posterior segment of the liver.Because hepatocellular carcinoma could not be completely excluded,this mass was resected.The tumor consisted of sheets of uniform cells with clear cytoplasm, perinuclear eosinophilic granules and round nuclei.These histological findings were consistent with liver cell adenoma. Background hepatic tissue appeared normal.After resection of the tumor,serum PIVKA-Ⅱ fell to within the normal range. An area of hepatocellular carcinoma (HCC) with a mid- trabecular pattern was immunohistochemically found,which was positive for PIVKA-Ⅱ.Sinusoidal endothelial cells were CD34-positive,containing scattered PIVKA-Ⅱ positive cells. This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.
基金Supported by the National Natural Science Foundation of China, No. 30171052 and No. 30572125
文摘We report a case of liver cell adenoma （LCA） in a 33-year-old female patient with special respect to its clonality status, pathogenic factors and differential diagnosis. The case was examined by histopathology, immunohistochemistry and a clonality assay based on X-chromosomal inactivation mosaicism in female somatic tissues and polymorphism at androgen receptor focus. The clinicopathological features of the reported cases from China and other countries were compared. The lesion was spherical, sizing 2 cm in its maximal dimension. Histologically, it was composed of cells arranged in cords, most of which were two-cell-thick and separated by sinusoids. Focal fatty change and excessive glycogen storage were observed. The tumor cells were round or polygonal in shape, resembling the surrounding parenchymal cells. Mitosis was not found. No portal tract, central vein or ductule was found within the lesion. The tumor tissue showed a positive reaction for cytokeratin （CK） 18, but not for CK19, vimentin, estrogen and progesterone receptors. Monoclonality was demonstrated for the lesion, confirming the diagnosis of an LCA. Clonality analysis is helpful for its distinction from focal nodular hyperplasia.K
文摘A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives.Radiological diagnostics showed the typical findings of liver cell adenoma(LCA).Dynamic computed tomography revealed that the tumor showed a homogenous enhancement in the arterial phase and almost the same enhancement as the surrounding liver parenchyma in the delayed phase.The tumor was found to contain fat on magnetic resonance imaging.A benign fat containing liver tumor was suggested.However,radiological findings altered,which caused us to suspect that a welldifferentiated hepatocellular carcinoma(HCC)containing fat was becoming dedifferentiated.Partial hepatectomy was performed and the pathological findings showed the typical findings of LCA.This case was an extremely rare LCA,which had no background of risk for LCA and developed the sequential alteration of the radiological findings to suspect well-differentiated HCC.
基金Supported by The Major National Science and Technology Projects for Infectious Diseases (11th and 12th Five Year, China),No. 2008ZX10002-007, No. 2012ZX10002-007the Foundation of Shaanxi Provincial Science and Technology Plan Projects,No. 2011K14-09-09
文摘AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.
文摘BACKGROUND: Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. METHODS: A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+ IL-17+ cells were measured by flow cytometry The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes Percentages of circulating Th17 cells were compared between the two groups and controls. RESULTS: The levels of circulating CD4+ IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56±0.43% versus 1.79±0.44% P<0.001). The frequency of CD4+ IL-17+ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002).CONCLUSION: Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.
文摘Objective:To study the correlation of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 expression with the illness in patients with chronic hepatitis b (CHB).Methods: A total of 48 patients who were diagnosed with chronic hepatitis b in Jianyang People's Hospital between July 2014 and January 2017 were selected as the CHB group of the research, 66 healthy volunteers who received physical examination during the same period were selected as control group, the peripheral blood was collected to determine Th17 cell surface CCR4, CCR6 and CXCR3 expression, and serum was collected to determine the levels of Th17 cytokines, liver function indexes and liver fibrosis indexes.Results: Peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity of CHB group were significantly higher than those of control group;serum IL-17, IL-21, IL-22, ALT, AST, GLB, HA, PC-Ⅲ, LN and C-Ⅳ levels of CHB group were significantly higher than those of control group and positively correlated with peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity while serum ALB level was significantly lower than that of control group and negatively correlated with peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity.Conclusion: The high expression of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 in patients with CHB can result in increased secretion of Th17 cytokines, liver function injury and liver fibrosis.
文摘We report the first case of a healthy 23-year-old female who underwent an interventional radiology-guided embolization of a hepatic adenoma, which resulted in a gas forming hepatic liver abscess and septicemia by Clostridium paraputrificum. A retrospective review of Clostridial liver abscesses was performed using a Pub Med literature search, and we found 57 clostridial hepatic abscess cases. The two most commonly reported clostridial species are C. perfringens and C. septicum(64.9% and 17.5% respectively). C. perfringens cases carried a mortality of 67.6% with median survival of 11 h, and 70.2% of the C. perfringens cases experienced hemolysis. All C. septicum cases were found to have underlying liver malignancy at the time of the presentation with a mortality of only 30%. The remaining cases were caused by various Clostridium species, and this cohort's clinical course was significantly milder when compared to the above C. perfringens and C. septicum cohorts.
文摘目的探讨不同病因所致肝衰竭患者外周血单个核细胞(PBMCs)HLA-DR m RNA及Th17和CD4^+CD25^+Treg细胞水平的变化及其意义。方法本研究纳入肝衰竭患者50例,其中乙型肝炎肝衰竭15例,药物性肝损伤12例,酒精性肝病13例,自身免疫性肝炎10例;慢性乙型肝炎患者17例和正常人10例。采用PCR法检测PBMCs中HLA-DR m RNA水平,使用流式细胞仪检测CD4^+CD25^+Treg和Th17细胞百分比。结果乙型肝炎肝衰竭患者HLA-DR m RNA水平为(134.5±15.2),显著高于药物性肝损伤组的(17.9±1.2)、酒精性肝病组的(19.6±2.0)和自身免疫性肝炎组的[(11.2±1.2),P<0.05];不同病因肝衰竭患者Th17和CD4^+CD25^+Treg细胞百分比[分别为(4.4±0.6)%和(3.9±0.6)%左右]的差异无统计学意义(P>0.05),但与慢性乙型肝炎[分别为(3.7±0.2)%和(6.1±0.4)%和正常人(2.1±0.7)%和(7.0±0.9)%比,均有显著性差异(P<0.05);对不同病因肝衰竭患者进行动态观察发现,19例死亡患者CD4^+CD25^+Treg细胞百分比呈持续下降,直至死亡,而31例生存患者则逐渐恢复至接近正常水平。结论外周血单个核细胞HLA-DR m RNA水平及Th17和CD4^+CD25^+Treg细胞百分比的变化与肝衰竭患者的病情密切相关,可作为判断肝衰竭严重程度及预后的指标。
基金This project was supported by grants from National Science Foundation of China Advanced Program (No. 81030007)National Science Foundation of China for Young Scholar (No.81100308/H0318)
文摘Recently,the Th17 cells and IL-17 have been shown to play a critical role in the immune-mediated liver injury in hepatitis B,while their functions in acute liver failure have not been well elucidated yet.In this study,we primarily investigated the role of IL-17 in the development of mouse hepatitis virus strain 3(MHV-3)-induced acute liver failure.IL-17 mRNA levels in liver tissue were quantified by using quantitative real-time polymerase chain reaction,and cytokine IL-17 levels in liver tissue and serum were determined by using ELISA in MHV-3-induced murine fulminant hepatitis model.The IL-17 expression levels on CD4 + T and CD8 + T cells were determined by using flow cytometry.The correlation between IL-17 level and liver injury was studied.Th17 associated cytokines were also investigated by intracellular staining.Our results showed that the IL-17 expression was significantly elevated in the liver and serum of BALB/cJ mice infected with MHV-3.Moreover,a time course study showed that the percentage of both IL-17-producing CD4 + T cells and IL-17-producing CD8 + T cells was increased remarkably in the liver starting from 48 h and peaked at 72 h post-infection.There was a close correlation between hepatic or serum IL-17 concentration and the severity of liver injury defined by ALT level,respectively.Th17 associated cytokines,IL-6,IL-21 and IL-22,were also increased significantly at 72 h post-infection.It was concluded that IL-17 may contribute to the pathogenesis of MHV-3-induced acute liver failure.
基金by grants from the National Key Research and Development Program of China(2017YFA0104500)the National Natural Science Foundation of China(81471525,31671244,and 31872734,Q.G.+2 种基金81601975,K.Z.)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT31039).
文摘Newborn animals require tightly regulated local and systemic immune environments to govern the development and maturation of multiple organs/tissues even though the immune system itself is far from mature during the neonatal period.Regulatory T cells(Tregs)are essential for maintaining immune tolerance/homeostasis and modulating inflammatory responses.The features of Tregs in the neonatal liver under steady-state conditions are not well understood.The present study aimed to investigate the phenotype,functions,and significance of neonatal Tregs in the liver.We found a wave of thymus-derived Treg influx into the liver during 1–2 weeks of age.Depletion of these Tregs between days 7 and 11 after birth rapidly resulted in Th1-type liver inflammation and metabolic disorder.More Tregs in the neonatal liver than in the spleen underwent MHC II-dependent activation and proliferation,and the liver Tregs acquired stronger suppressive functions.The transcriptomic profile of these neonatal liver Tregs showed elevated expression of PPARγand T-bet and features of Tregs that utilize lipid metabolic machinery and are capable of regulating Th1 responses.The accumulation of Tregs with unique features in the neonatal liver is critical to ensure self-tolerance and liver maturation.
