AIM: To investigate the expression of fragile histidine triad (FHIT) gene protein, Fhit, which is recently thought to be a candidate tumor suppressor. Abnormal expression of fragile histidine triad has been found in a...AIM: To investigate the expression of fragile histidine triad (FHIT) gene protein, Fhit, which is recently thought to be a candidate tumor suppressor. Abnormal expression of fragile histidine triad has been found in a variety of human cancers,but little is known about its expression in human hepatocellular carcinogenesis and evolution.METHODS: Sections of 83 primary human hepatocellular carcionoma with corresponding para-neoplastic liver tissue and 10 normal liver tissue were evaluated immunohistochemically for Fhit protein expression.RESULTS: All normal liver tissue and para-neoplastic liver tissue showed a strong expression of Fhit, whereas 50 of 83(65.0 %) carcinomas showed a marked loss or absence of Fhit expression. The differences of Fhit expression between carcinoma and normal or para-neoplastic liver tissue werehighly significant (P=0.000). The proportion of carcinomas with reduced Fhit expression showed an increasing trend (a) with decreasing differentiation or higher histological grade (P=0.219); (b) in tumors with higher clinical stage Ⅲ and ⅣV (91.3 %, P=0.000), compared with tumors with lower stage Ⅰ and Ⅱ (27.6 %); and (c) in cancers with bigger tumor size (＞50 mm) (75.0 %, P=0.017), compared withsmaller tumor size (≤ 50 mm).
CONCLUSION: FHIT inactivation seems to be both an earlyand a later event, associated with carcinogenesis andprogression to more aggressive hepatocellular carcinomas.Thus, evaluation of Fhit expression by immunohistochemistryin hepatocellular carcinoma may provide important diagnosticand prognostic information in clinical application.展开更多
Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothe...Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1 alpha-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.展开更多
BACKGROUND Endoscopic sphincterotomy(EST) for the management of common bile duct stones(CBDS) is used increasingly widely because it is a minimally invasive procedure. However, some clinical practitioners argued that ...BACKGROUND Endoscopic sphincterotomy(EST) for the management of common bile duct stones(CBDS) is used increasingly widely because it is a minimally invasive procedure. However, some clinical practitioners argued that EST may be complicated by post-endoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP) and accompanied by a higher recurrence of CBDS than open choledochotomy(OCT). Whether any differences in outcomes exist between these two approaches for treating CBDS has not been thoroughly elucidated to date.AIM To compare the outcomes of EST vs OCT for the management of CBDS and to clarify the risk factors associated with stone recurrence.METHODS Patients who underwent EST or OCT for CBDS between January 2010 and December 2012 were enrolled in this retrospective study. Follow-up data were obtained through telephone or by searching the medical records. Statistical analysis was carried out for 302 patients who had a follow-up period of at least 5 years or had a recurrence. Propensity score matching(1:1) was performed to adjust for clinical differences. A logistic regression model was used to identify potential risk factors for recurrence, and a receiver operating characteristic(ROC)curve was generated for qualifying independent risk factors.RESULTS In total, 302 patients undergoing successful EST(n = 168) or OCT(n = 134) were enrolled in the study and were followed for a median of 6.3 years. After propensity score matching, 176 patients remained, and all covariates were balanced. EST was associated with significantly shorter time to relieving biliary obstruction, anesthetic duration, procedure time, and hospital stay than OCT(P <0.001). The number of complete stone clearance sessions increased significantly in the EST group(P = 0.009). The overall incidence of complications and mortality did not differ significantly between the two groups. Recurrent CBDS occurred in18.8%(33/176) of the patients overall, but no difference was found between the EST(20.5%, 18/88) and OCT(17.0%, 15/88) groups. Factors as展开更多
In plants,high disease resistance often results in a reduction of yield.Therefore,breeding crops with balanced yield and disease resistance has become a major challenge.Recently,microRNA(miRNA)-mediated R gene turnove...In plants,high disease resistance often results in a reduction of yield.Therefore,breeding crops with balanced yield and disease resistance has become a major challenge.Recently,microRNA(miRNA)-mediated R gene turnover has been shown to be a protective mechanism used by plants to prevent autoimmunity in the absence of pathogens.However,whether these miRNAs play a role in plant growth and how miRNA-mediated R gene turnover responds to pathogen infection have rarely been explored.Here,we found that a Brassica miRNA,miR1885,targets both an immune receptor gene and a development-related gene for negative regulation through distinct modes of action.MiR1885 directly silences the TIR-NBS-LRR class of R gene BraTNL1 but represses the expression of the photosynthesis-related gene BraCP24 by targeting the Trans-Acting Silencing(TAS)gene BraTIR1 for trans-acting small interfering RNAs(tasiRNAs)-mediated silencing.We found that,under natural conditions,miR1885 was kept at low levels to maintain normal development and basal immunity but peaked during the floral transition to promote flowering.Interestingly,upon Turnip mosaic virus(TuMV)infection,miR1885-dependent trans-acting silencing of BraCP24 was enhanced to speed up the floral transition,whereas miR1885-mediated R gene turnover was overcome by TuMV-induced BraTNL1 expression,reflecting precise regulation of the arms race between plants and pathogens.Collectively,our results demonstrate that a single Brassica miRNA dynamically regulates both innate immunity and plant growth and responds to viral infection,revealing that Brassica plants have developed a sophisticated mechanism in modulating the interplay between growth,immunity,and pathogen infection.展开更多
文摘AIM: To investigate the expression of fragile histidine triad (FHIT) gene protein, Fhit, which is recently thought to be a candidate tumor suppressor. Abnormal expression of fragile histidine triad has been found in a variety of human cancers,but little is known about its expression in human hepatocellular carcinogenesis and evolution.METHODS: Sections of 83 primary human hepatocellular carcionoma with corresponding para-neoplastic liver tissue and 10 normal liver tissue were evaluated immunohistochemically for Fhit protein expression.RESULTS: All normal liver tissue and para-neoplastic liver tissue showed a strong expression of Fhit, whereas 50 of 83(65.0 %) carcinomas showed a marked loss or absence of Fhit expression. The differences of Fhit expression between carcinoma and normal or para-neoplastic liver tissue werehighly significant (P=0.000). The proportion of carcinomas with reduced Fhit expression showed an increasing trend (a) with decreasing differentiation or higher histological grade (P=0.219); (b) in tumors with higher clinical stage Ⅲ and ⅣV (91.3 %, P=0.000), compared with tumors with lower stage Ⅰ and Ⅱ (27.6 %); and (c) in cancers with bigger tumor size (＞50 mm) (75.0 %, P=0.017), compared withsmaller tumor size (≤ 50 mm).
CONCLUSION: FHIT inactivation seems to be both an earlyand a later event, associated with carcinogenesis andprogression to more aggressive hepatocellular carcinomas.Thus, evaluation of Fhit expression by immunohistochemistryin hepatocellular carcinoma may provide important diagnosticand prognostic information in clinical application.
基金Supported by National Natural Science Foundation of China,No.81260504,No.81660151 and No.81660751Science Foundation of Science Commission of Jiangxi Province,China,No.20161BBG70067School Teaching Reform Fund of Nanchang University,No.NCUJGLX-14-1-111
文摘Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1 alpha-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.
文摘BACKGROUND Endoscopic sphincterotomy(EST) for the management of common bile duct stones(CBDS) is used increasingly widely because it is a minimally invasive procedure. However, some clinical practitioners argued that EST may be complicated by post-endoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP) and accompanied by a higher recurrence of CBDS than open choledochotomy(OCT). Whether any differences in outcomes exist between these two approaches for treating CBDS has not been thoroughly elucidated to date.AIM To compare the outcomes of EST vs OCT for the management of CBDS and to clarify the risk factors associated with stone recurrence.METHODS Patients who underwent EST or OCT for CBDS between January 2010 and December 2012 were enrolled in this retrospective study. Follow-up data were obtained through telephone or by searching the medical records. Statistical analysis was carried out for 302 patients who had a follow-up period of at least 5 years or had a recurrence. Propensity score matching(1:1) was performed to adjust for clinical differences. A logistic regression model was used to identify potential risk factors for recurrence, and a receiver operating characteristic(ROC)curve was generated for qualifying independent risk factors.RESULTS In total, 302 patients undergoing successful EST(n = 168) or OCT(n = 134) were enrolled in the study and were followed for a median of 6.3 years. After propensity score matching, 176 patients remained, and all covariates were balanced. EST was associated with significantly shorter time to relieving biliary obstruction, anesthetic duration, procedure time, and hospital stay than OCT(P <0.001). The number of complete stone clearance sessions increased significantly in the EST group(P = 0.009). The overall incidence of complications and mortality did not differ significantly between the two groups. Recurrent CBDS occurred in18.8%(33/176) of the patients overall, but no difference was found between the EST(20.5%, 18/88) and OCT(17.0%, 15/88) groups. Factors as
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences,China(XDB27040203)by the National Science Foundation of China,China(no.31570155)The work was also supported by the National Natural Science Foundation of China,China(no.31970157 to Y.-Y.F.and no.31730078 to H.-S.G.).
文摘In plants,high disease resistance often results in a reduction of yield.Therefore,breeding crops with balanced yield and disease resistance has become a major challenge.Recently,microRNA(miRNA)-mediated R gene turnover has been shown to be a protective mechanism used by plants to prevent autoimmunity in the absence of pathogens.However,whether these miRNAs play a role in plant growth and how miRNA-mediated R gene turnover responds to pathogen infection have rarely been explored.Here,we found that a Brassica miRNA,miR1885,targets both an immune receptor gene and a development-related gene for negative regulation through distinct modes of action.MiR1885 directly silences the TIR-NBS-LRR class of R gene BraTNL1 but represses the expression of the photosynthesis-related gene BraCP24 by targeting the Trans-Acting Silencing(TAS)gene BraTIR1 for trans-acting small interfering RNAs(tasiRNAs)-mediated silencing.We found that,under natural conditions,miR1885 was kept at low levels to maintain normal development and basal immunity but peaked during the floral transition to promote flowering.Interestingly,upon Turnip mosaic virus(TuMV)infection,miR1885-dependent trans-acting silencing of BraCP24 was enhanced to speed up the floral transition,whereas miR1885-mediated R gene turnover was overcome by TuMV-induced BraTNL1 expression,reflecting precise regulation of the arms race between plants and pathogens.Collectively,our results demonstrate that a single Brassica miRNA dynamically regulates both innate immunity and plant growth and responds to viral infection,revealing that Brassica plants have developed a sophisticated mechanism in modulating the interplay between growth,immunity,and pathogen infection.
