AIM： To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism ofT lymphocyte infiltration regulated by CXCL16. METHODS： Immunological liver injury in ...AIM： To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism ofT lymphocyte infiltration regulated by CXCL16. METHODS： Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide. Expression pattern and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated. RESULTS, The murine immunological liver injury model was successfully established, CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×10^7 to 3.52×10^6/liver, compared with control Ab treatment. CONCLUSION： CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.展开更多
BACKGROUND Tumor-infiltrating lymphocytes(TILs)constitute a prognostic factor in hepatocellular carcinoma(HCC).However,different methods of assessing TILs have various pre-analytical,analytical,and post-analytical cha...BACKGROUND Tumor-infiltrating lymphocytes(TILs)constitute a prognostic factor in hepatocellular carcinoma(HCC).However,different methods of assessing TILs have various pre-analytical,analytical,and post-analytical challenges.The evaluation of TILs in hematoxylin and eosin(H&E)-stained tumor sections proposed by the International Immuno-Oncology Biomarker Working Group was demonstrated to be a reproducible,affordable and easily applied method in many tumors.AIM To evaluate the prognostic significance of TILs in H&E-stained slides of HCCs.METHODS This was a retrospective study performed in the hospital.HCC patients who underwent liver resection between 2015 and 2017 in Zhongshan Hospital were enrolled in this study.Patients who experienced recurrence or received therapy in addition to antiviral therapy before surgery at this time were excluded.A total of 204 patients were enrolled in the study.The ILs were counted manually in tumor sections stained with H&E under an optical microscope at 400×.The ILs were assessed separately in the center of the tumor(TILs^(CT)),the invasive front(TILs^(IF)),and peritumor(PILs)areas.Univariate and multivariate survival analyses were performed using a Cox regression model.P<0.05 was considered statistically significant and all P-values were two-sided.RESULTS Among the 204 patients,univariate analysis indicated that macrovascular invasion(MaVI)(P=0.001),microvascular invasion(MVI)(P=0.012),multiple tumors(P=0.008),large tumors(>10 cm)(P=0.001),absence of a tumor capsule(P=0.026),macrotrabecular histological subtype(P=0.001),low density of TILs^(CT)(P=0.039),TILs^(IF)(P=0.014),and PILs(P=0.010)were predictors of progressionfree survival(PFS).Cox multivariate analysis indicated that MaVI(P=0.009),absence of a tumor capsule(P=0.031),low-density of TILs^(IF)(P=0.047)and PILs(P=0.0495)were independent predictors of PFS.A three-category analysis was carried out by combining TILs^(CT),TILs^(IF),and PILs,after which HCCs were classified into immune^(high)[(TILs^(CT))^(high),(TILs^(IF))^(hig展开更多
Autoimmune pancreatitis(AIP)is a rare form of pan-creatitis characterized by prominent lymphocyte inf iltration and pancreatic f ibrosis resulting in organ dysfunc-tion.The pathogenesis and pathology of AIP remain unk...Autoimmune pancreatitis(AIP)is a rare form of pan-creatitis characterized by prominent lymphocyte inf iltration and pancreatic f ibrosis resulting in organ dysfunc-tion.The pathogenesis and pathology of AIP remain unknown.A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas,elevated IgG levels,and negative autoimmune antibody responses.A pylorus-preserving pancreatoduodenectomy was per-formed and a pancreatic tumor was suspected.Howev-er,periductal lymphoplasmacytic inf iltration and f ibrosis were found in the head of pancreas and nearby organs instead of tumor cells.Four months after surgery,the patient was readmitted because of reoccurrence ofsevere jaundice and sustained abdominal distension.Prednisone 30 mg/d was administered orally as an AIP was suspected.One and a half months later,the symp-toms of the patient disappeared,and globulin,amino-transferase and bilirubin levels decreased signif icantly.Over a 9-mo follow-up period,the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition.We further demonstrated dominant CD3+/CD8+ populations,CD20+ cells and a few CD4+ cells in the pancreatic parenchyma,duo-denum and gallbladder wall by immunohistochemical assay.This AIP case presented with signif icant CD8+ T lymphocyte inf iltration in the pancreas and extra-pan-creatic lesions,indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.展开更多
基金Supported by the National Natural Science Foundation of China,No. 30230320National Science Fund for Distinguished Young Scholars from NSFC, No. 39925031National High Technology Research and Development Program of China, 863 grant 2004 AA215242Major State Basic Research Development Program of China, No. 2001CB510005partially by E-Institute of Shanghai Universities
文摘AIM： To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism ofT lymphocyte infiltration regulated by CXCL16. METHODS： Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide. Expression pattern and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated. RESULTS, The murine immunological liver injury model was successfully established, CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×10^7 to 3.52×10^6/liver, compared with control Ab treatment. CONCLUSION： CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.
文摘BACKGROUND Tumor-infiltrating lymphocytes(TILs)constitute a prognostic factor in hepatocellular carcinoma(HCC).However,different methods of assessing TILs have various pre-analytical,analytical,and post-analytical challenges.The evaluation of TILs in hematoxylin and eosin(H&E)-stained tumor sections proposed by the International Immuno-Oncology Biomarker Working Group was demonstrated to be a reproducible,affordable and easily applied method in many tumors.AIM To evaluate the prognostic significance of TILs in H&E-stained slides of HCCs.METHODS This was a retrospective study performed in the hospital.HCC patients who underwent liver resection between 2015 and 2017 in Zhongshan Hospital were enrolled in this study.Patients who experienced recurrence or received therapy in addition to antiviral therapy before surgery at this time were excluded.A total of 204 patients were enrolled in the study.The ILs were counted manually in tumor sections stained with H&E under an optical microscope at 400×.The ILs were assessed separately in the center of the tumor(TILs^(CT)),the invasive front(TILs^(IF)),and peritumor(PILs)areas.Univariate and multivariate survival analyses were performed using a Cox regression model.P<0.05 was considered statistically significant and all P-values were two-sided.RESULTS Among the 204 patients,univariate analysis indicated that macrovascular invasion(MaVI)(P=0.001),microvascular invasion(MVI)(P=0.012),multiple tumors(P=0.008),large tumors(>10 cm)(P=0.001),absence of a tumor capsule(P=0.026),macrotrabecular histological subtype(P=0.001),low density of TILs^(CT)(P=0.039),TILs^(IF)(P=0.014),and PILs(P=0.010)were predictors of progressionfree survival(PFS).Cox multivariate analysis indicated that MaVI(P=0.009),absence of a tumor capsule(P=0.031),low-density of TILs^(IF)(P=0.047)and PILs(P=0.0495)were independent predictors of PFS.A three-category analysis was carried out by combining TILs^(CT),TILs^(IF),and PILs,after which HCCs were classified into immune^(high)[(TILs^(CT))^(high),(TILs^(IF))^(hig
文摘Autoimmune pancreatitis(AIP)is a rare form of pan-creatitis characterized by prominent lymphocyte inf iltration and pancreatic f ibrosis resulting in organ dysfunc-tion.The pathogenesis and pathology of AIP remain unknown.A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas,elevated IgG levels,and negative autoimmune antibody responses.A pylorus-preserving pancreatoduodenectomy was per-formed and a pancreatic tumor was suspected.Howev-er,periductal lymphoplasmacytic inf iltration and f ibrosis were found in the head of pancreas and nearby organs instead of tumor cells.Four months after surgery,the patient was readmitted because of reoccurrence ofsevere jaundice and sustained abdominal distension.Prednisone 30 mg/d was administered orally as an AIP was suspected.One and a half months later,the symp-toms of the patient disappeared,and globulin,amino-transferase and bilirubin levels decreased signif icantly.Over a 9-mo follow-up period,the dose of prednisone was gradually decreased to 10 mg/d and the patient remained in good condition.We further demonstrated dominant CD3+/CD8+ populations,CD20+ cells and a few CD4+ cells in the pancreatic parenchyma,duo-denum and gallbladder wall by immunohistochemical assay.This AIP case presented with signif icant CD8+ T lymphocyte inf iltration in the pancreas and extra-pan-creatic lesions,indicating that this cell population may be more important in mediating AIP pathogenesis than previously known and that AIP might be a poorly defined autoimmune disease with heterogeneous pathogenesis.
