BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs ...BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.AIM To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.METHODS A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups:A(15 cases with desmoplastic liver metastasis)and B(14 cases with replacement liver metastasis).Clinical information was obtained from patients’charts.Mismatch repair proteins,BRAFV600E,and PD-L1 were evaluated by immunohistochemistry.Five cases were selected randomly from each group for whole exome sequencing(WES)analysis.RESULTS In the primary tumor,expanding growth pattern,low tumor budding score(TBS),and Crohn’s disease-like response(CDR)were associated with desmoplastic liver metastasis and better overall survival,whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival(P<0.05).On WES analysis,primary carcinoma with desmoplastic liver metastasis showed mutations in APC(4/5);TP53(3/5);KRAS,PIK3CA,and FAT4(2/5);BRCA-1,BRCA2,BRAF,and DNAH5(1/5),whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53(3/5);KRAS,FAT4,DNH5,SMAD,ERBB2,ERBB3,LRP1,and SDK1(1/5).CONCLUSION The HGPs,TBS,and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis,response to therapy,and patients’prognosis.展开更多
Objectives: To compare the risk of death and recurrent congestive heart failure in elderly patients prescribed celecoxib, rofecoxib, or non-steroidal anti-inflammatory drugs(NSAIDs) and to determine whether there are ...Objectives: To compare the risk of death and recurrent congestive heart failure in elderly patients prescribed celecoxib, rofecoxib, or non-steroidal anti-inflammatory drugs(NSAIDs) and to determine whether there are class differences between celecoxib and rofecoxib. Design: Population based retrospective cohort study. Setting: Databases of hospital discharge summaries and prescription drug claims in Quebec. Participants: 2256 patients aged 66 or more prescribed celecoxib, rofecoxib, or a NSAID after an index admission for congestive heart failure between April 2000 and March 2002. Main outcome measures: Time to all cause death and recurrent congestive heart failure, combined and separately. Results: The risk of death and recurrent congestive heart failure combined was higher in patients prescribed NSAIDs or rofexocib than in those prescribed celecoxib(hazard ratio 1.26, 95%confidence interval 1.00 to 1.57 and 1.27, 1.09 to 1.49, respectively). The findings were similar when the outcomes were assessed separately. In pairwise analysis, the risks of death and recurrent congestive heart failure, combined and separate, were similar between patients prescribed NSAIDs and rofecoxib. Conclusions: Celecoxib seems safer than rofecoxib and NSAIDs in elderly patients with congestive heart failure. Differences were found among cyclo-oxygenase-2 inhibitors.展开更多
Objective: We aimed to observe the effects of loganin(Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase(AMPK) signaling in obese mice.Methods: A hig...Objective: We aimed to observe the effects of loganin(Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase(AMPK) signaling in obese mice.Methods: A high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research(ICR) mice. Body weight was measured weekly and fasting blood glucose(FBG) was determined every 2 weeks. Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed. The serum levels of total cholesterol(TC), triglyceride, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol(LDL-C), and free fatty acids(FFA) were measured. The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting, and gut microbiota were characterized using 16S rDNA sequencing.Results: Log significantly decreased the body weight and the FBG in obese mice(P <.05), and it could restore FBG to normal levels. The total cholesterol, LDL-C, and FFA levels were significantly reduced by Log compared with the obese controls(TC: P =.0020;LDL-C: P =.0233;FFA: P =.0127), and the glucose tolerance of animals was significantly improved(P =.0477). The western blot results showed that Log could upregulate the protein expression of Adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPKa), Sirtuin 1(SIRT1), and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1a) in skeletal muscle tissue of obese mice. 16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice.Conclusions: Log was effective in reducing body weight and improving glucolipid metabolism in obese mice, probably through activating AMPK signaling and regulating intestinal microbial diversity.展开更多
Objective:To determine the effects of ginsenoside rg3 on the body weight of C57BL/6J obese mice and to investigate its underlying weight loss mechanisms with a focus on white fat browning-related factors.Methods:Eight...Objective:To determine the effects of ginsenoside rg3 on the body weight of C57BL/6J obese mice and to investigate its underlying weight loss mechanisms with a focus on white fat browning-related factors.Methods:Eight-week-old C57BL/6J male mice were fed a high-fat diet for 12 successive weeks to construct the obese model.C57BL/6J male mice were fed a standard chow diet to construct normal control group.After 8 weeks of intervention with ginsenoside rg3,the food intake,body weight,body fat mass,blood sugar,and lipid profiles of the mice in each group were detected.Hematoxylin and eosin(HE)staining was used to observe the histological morphology of the adipose tissues.Real-time polymerase chain reaction(RT-PCR)and Western blotting(WB)were applied to detect the gene and protein expression levels of peroxisome proliferators-activated receptor gama(PPARg),Peroxisome proliferatoractivated receptor-gamma coactivator-1alpha(PGC-1a),PR domain containing 16(PRDM16),and uncoupling protein 1(UCP-1).Results:Compared to normal control group mice,the body weight,food intake,body fat composition,and blood lipid levels of model group mice increased significantly.After 8 weeks of intervention with ginsenoside rg3,body weight,body fat composition,food intake,and blood lipid profiles decreased.HE staining showed that ginsenoside rg3 can improve white adipocyte hypertrophy to a certain extent.RTPCR and WB demonstrated that ginsenoside rg3 can increase the mRNA and protein expression levels of PPARg,PGC-1a,PRDM16,and UCP-1 in the adipose tissues of obese mice.Conclusion:The weight reduction effect of ginsenoside rg3 may be related to the promotion of white fat browning.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive te...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients,namely controlled attenuation parameter(CAP)and the serum biomarker cytokeratin 18(CK-18).We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology.METHODS We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018.Serial measurements of CK-18 and CAP were recorded.NAFLD and NASH were diagnosed by CAP≥270 dB/m,and a combination of CAP≥270 dB/m with CK-18>130.5 U/L,respectively.Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards.RESULTS Overall,40 liver transplant recipients(mean age 57 years;70%males)were included.During a median follow-up of 16.8 mo(interquartile range 15.6-18.0),63.0%and 48.5%of patients developed NAFLD and NASH,respectively.On multivariable analysis,after adjusting for sex and alanine aminotransferase,body mass index was an independent predictor of development of NAFLD[adjusted hazard ratio(aHR):1.21,95%confidence interval(CI):1.04-1.41;P=0.01]and NASH(aHR:1.26,95%CI:1.06-1.49;P<0.01).Compared to liver histology,CAP had a 76%accuracy to diagnose NAFLD,while the accuracy of CAP plus CK-18 to diagnose NASH was 82%.CONCLUSION NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo.Close follow-up and nutritional counselling should be planned in overweight patients.展开更多
基金the Human Resources Development Program for the Outstanding Talents in The Fifth People’s Hospital of Shanghai,Fudan University,No.2017WYRCJY09the Key Medical Speciality of The Fifth People’s Hospital of Shanghai,Fudan University,No.2017WY202K08
文摘BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.AIM To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.METHODS A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups:A(15 cases with desmoplastic liver metastasis)and B(14 cases with replacement liver metastasis).Clinical information was obtained from patients’charts.Mismatch repair proteins,BRAFV600E,and PD-L1 were evaluated by immunohistochemistry.Five cases were selected randomly from each group for whole exome sequencing(WES)analysis.RESULTS In the primary tumor,expanding growth pattern,low tumor budding score(TBS),and Crohn’s disease-like response(CDR)were associated with desmoplastic liver metastasis and better overall survival,whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival(P<0.05).On WES analysis,primary carcinoma with desmoplastic liver metastasis showed mutations in APC(4/5);TP53(3/5);KRAS,PIK3CA,and FAT4(2/5);BRCA-1,BRCA2,BRAF,and DNAH5(1/5),whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53(3/5);KRAS,FAT4,DNH5,SMAD,ERBB2,ERBB3,LRP1,and SDK1(1/5).CONCLUSION The HGPs,TBS,and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis,response to therapy,and patients’prognosis.
文摘Objectives: To compare the risk of death and recurrent congestive heart failure in elderly patients prescribed celecoxib, rofecoxib, or non-steroidal anti-inflammatory drugs(NSAIDs) and to determine whether there are class differences between celecoxib and rofecoxib. Design: Population based retrospective cohort study. Setting: Databases of hospital discharge summaries and prescription drug claims in Quebec. Participants: 2256 patients aged 66 or more prescribed celecoxib, rofecoxib, or a NSAID after an index admission for congestive heart failure between April 2000 and March 2002. Main outcome measures: Time to all cause death and recurrent congestive heart failure, combined and separately. Results: The risk of death and recurrent congestive heart failure combined was higher in patients prescribed NSAIDs or rofexocib than in those prescribed celecoxib(hazard ratio 1.26, 95%confidence interval 1.00 to 1.57 and 1.27, 1.09 to 1.49, respectively). The findings were similar when the outcomes were assessed separately. In pairwise analysis, the risks of death and recurrent congestive heart failure, combined and separate, were similar between patients prescribed NSAIDs and rofecoxib. Conclusions: Celecoxib seems safer than rofecoxib and NSAIDs in elderly patients with congestive heart failure. Differences were found among cyclo-oxygenase-2 inhibitors.
基金supported by the Qi Huang Scholars Program of the State Administration of Traditional Chinese Medicine(10400633210005)the National Natural Science Foundation of China (NSFC82174329&NSFC81503540)+1 种基金the Key Drug Development Program (2012ZX09103201-005)the Key Research Project of Beijing University of Chinese Medicine (2020-JYB-ZDGG-029)。
文摘Objective: We aimed to observe the effects of loganin(Log) on serum glycolipid levels and probe the mechanisms focusing on intestinal flora and AMP-activated protein kinase(AMPK) signaling in obese mice.Methods: A high-fat diet was given for 12 consecutive weeks to generate the obesity model in institute of cancer research(ICR) mice. Body weight was measured weekly and fasting blood glucose(FBG) was determined every 2 weeks. Both the oral glucose tolerance test and the intraperitoneal insulin tolerance test were performed. The serum levels of total cholesterol(TC), triglyceride, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol(LDL-C), and free fatty acids(FFA) were measured. The expression of key proteins in the AMPK signaling pathway in skeletal muscle tissue was detected by immunoblotting, and gut microbiota were characterized using 16S rDNA sequencing.Results: Log significantly decreased the body weight and the FBG in obese mice(P <.05), and it could restore FBG to normal levels. The total cholesterol, LDL-C, and FFA levels were significantly reduced by Log compared with the obese controls(TC: P =.0020;LDL-C: P =.0233;FFA: P =.0127), and the glucose tolerance of animals was significantly improved(P =.0477). The western blot results showed that Log could upregulate the protein expression of Adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPKa), Sirtuin 1(SIRT1), and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha(PGC1a) in skeletal muscle tissue of obese mice. 16S rDNA sequencing indicated that Log reduced the diversity of the gut flora in feces and altered the floral composition of obese mice.Conclusions: Log was effective in reducing body weight and improving glucolipid metabolism in obese mice, probably through activating AMPK signaling and regulating intestinal microbial diversity.
基金This study received support from the Key Research Project of Beijing University of Chinese Medicine(2020-JYB-ZDGG-029)the National Natural Science Foundation of China(81274041 and 81503540)+1 种基金the Key Drug Development Programme of the Ministry of Science and Technology(20122X09103201-005)the International Cooperation Projects of the Ministry of Education(2011DFA30920).
文摘Objective:To determine the effects of ginsenoside rg3 on the body weight of C57BL/6J obese mice and to investigate its underlying weight loss mechanisms with a focus on white fat browning-related factors.Methods:Eight-week-old C57BL/6J male mice were fed a high-fat diet for 12 successive weeks to construct the obese model.C57BL/6J male mice were fed a standard chow diet to construct normal control group.After 8 weeks of intervention with ginsenoside rg3,the food intake,body weight,body fat mass,blood sugar,and lipid profiles of the mice in each group were detected.Hematoxylin and eosin(HE)staining was used to observe the histological morphology of the adipose tissues.Real-time polymerase chain reaction(RT-PCR)and Western blotting(WB)were applied to detect the gene and protein expression levels of peroxisome proliferators-activated receptor gama(PPARg),Peroxisome proliferatoractivated receptor-gamma coactivator-1alpha(PGC-1a),PR domain containing 16(PRDM16),and uncoupling protein 1(UCP-1).Results:Compared to normal control group mice,the body weight,food intake,body fat composition,and blood lipid levels of model group mice increased significantly.After 8 weeks of intervention with ginsenoside rg3,body weight,body fat composition,food intake,and blood lipid profiles decreased.HE staining showed that ginsenoside rg3 can improve white adipocyte hypertrophy to a certain extent.RTPCR and WB demonstrated that ginsenoside rg3 can increase the mRNA and protein expression levels of PPARg,PGC-1a,PRDM16,and UCP-1 in the adipose tissues of obese mice.Conclusion:The weight reduction effect of ginsenoside rg3 may be related to the promotion of white fat browning.
基金the Canadian Donation and Transplantation Research Program of the Canadian Society of Transplantation(grant competition 2014)Sebastiani G is supported by a Senior Salary Award from Fonds de la Recherche en Santédu Quebéc(FRQS)(No.#296306).
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH)seem common after liver transplantation.AIM To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients,namely controlled attenuation parameter(CAP)and the serum biomarker cytokeratin 18(CK-18).We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology.METHODS We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018.Serial measurements of CK-18 and CAP were recorded.NAFLD and NASH were diagnosed by CAP≥270 dB/m,and a combination of CAP≥270 dB/m with CK-18>130.5 U/L,respectively.Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards.RESULTS Overall,40 liver transplant recipients(mean age 57 years;70%males)were included.During a median follow-up of 16.8 mo(interquartile range 15.6-18.0),63.0%and 48.5%of patients developed NAFLD and NASH,respectively.On multivariable analysis,after adjusting for sex and alanine aminotransferase,body mass index was an independent predictor of development of NAFLD[adjusted hazard ratio(aHR):1.21,95%confidence interval(CI):1.04-1.41;P=0.01]and NASH(aHR:1.26,95%CI:1.06-1.49;P<0.01).Compared to liver histology,CAP had a 76%accuracy to diagnose NAFLD,while the accuracy of CAP plus CK-18 to diagnose NASH was 82%.CONCLUSION NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo.Close follow-up and nutritional counselling should be planned in overweight patients.
