Objective： To compare the survival outcomes of transabdominal （TA） and transthoracic （TT） surgical approaches in patients with Siewert-II/III esophagogastric junction adenocarcinoma. Methods： This retrospective ...Objective： To compare the survival outcomes of transabdominal （TA） and transthoracic （TT） surgical approaches in patients with Siewert-II/III esophagogastric junction adenocarcinoma. Methods： This retrospective study was conducted in patients with Siewert-II/III esophagogastric junction adenocarcinoma who underwent either TT or TA operations in the West China Hospital between January 2006 and December 2009. Results： A total of 308 patients （109 in the TT and 199 in the TA groups） were included in this study with a follow-up rate of 87.3%. The median （P25, P75） number of harvested perigastric lymph nodes was 8 （5, 10） in the TT group and 23 （16, 34） in the TA group （P〈0.001）, and the number of positive perigastric lymph nodes was 2 （0, 5） in the TT group and 3 （1, 8） in the TA group （P〈0.004）. The 5-year overall survival （OS） rate was 36% in the TT group and 51% in the TA group （P=0.005）. Subgroup analysis by Siewert classification showed that 5-year OS rates for patients with Siewert II tumors were 38% and 48% in TT and TA groups, respectively （P=0.134）, whereas the 5-year OS rate for patients with Siewert III tumors was significantly lower in the TT group than that in the TA group （33% vs. 53%; P=0.010）. Multivariate analysis indicated that N2 and N3 stages, RI/R2 resection and a TT surgical approach were prognostic factors for poor OS. Conclusions： Improved perigastric lymph node dissection may be the main reason for better survival outcomes observed with a TA gastrectomy approach than with TT gastrectomy for Siewert III tumor patients.展开更多
Background:Knee osteoarthritis(OA)is still challenging to prevent or treat.Enhanced endoplasmic reticulum(ER)stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration.This study aim...Background:Knee osteoarthritis(OA)is still challenging to prevent or treat.Enhanced endoplasmic reticulum(ER)stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration.This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms,which have rarely been reported.Methods:The expression of the histone methyltransferase enhancer of zeste homolog 2(EZH2),microRNA-142-3p(miR-142-3p),and high mobility group box 1(HMGB1)and the levels of ER stress,pyroptosis,and metabolic markers in normal and OA chondrocytes were investigated by western blotting,quantitative polymerase chain reaction,immunohistochemistry,fluorescence in situ hybridization,fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone(FAM-YVAD-FMK)/Hoechst 33342/propidium iodide(PI)staining,lactate dehydrogenase(LDH)release assays,and cell viability assessments.The effects of EZH2,miR-142-3p,and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation,luciferase reporters,gain/loss-of-function assays,and rescue assays in interleukin(IL)-1β-induced OA chondrocytes.The mechanistic contribution of EZH2,miR-142-3p,and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically,histologically,and immunohistochemically in surgically induced OA rats.Results:Increased EZH2 and HMGB1,decreased miR-142-3p,enhanced ER stress,and activated pyroptosis in chondrocytes were associated with OA occurrence and progression.EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes.EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation,and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3′-UTR of the HMGB1 gene.Moreover,ER stress mediated the effects of EZH2,miR-142-3p,and HMGB1 on chondrocyte pyroptosis.In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2,miR-142-3p,and HMGB1 and their effects on chondrocyte ER stress and pyroptosis.Conclusions:A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA,contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.展开更多
基金supported by National Natural Science Foundation of China(No.81372344)
文摘Objective： To compare the survival outcomes of transabdominal （TA） and transthoracic （TT） surgical approaches in patients with Siewert-II/III esophagogastric junction adenocarcinoma. Methods： This retrospective study was conducted in patients with Siewert-II/III esophagogastric junction adenocarcinoma who underwent either TT or TA operations in the West China Hospital between January 2006 and December 2009. Results： A total of 308 patients （109 in the TT and 199 in the TA groups） were included in this study with a follow-up rate of 87.3%. The median （P25, P75） number of harvested perigastric lymph nodes was 8 （5, 10） in the TT group and 23 （16, 34） in the TA group （P〈0.001）, and the number of positive perigastric lymph nodes was 2 （0, 5） in the TT group and 3 （1, 8） in the TA group （P〈0.004）. The 5-year overall survival （OS） rate was 36% in the TT group and 51% in the TA group （P=0.005）. Subgroup analysis by Siewert classification showed that 5-year OS rates for patients with Siewert II tumors were 38% and 48% in TT and TA groups, respectively （P=0.134）, whereas the 5-year OS rate for patients with Siewert III tumors was significantly lower in the TT group than that in the TA group （33% vs. 53%; P=0.010）. Multivariate analysis indicated that N2 and N3 stages, RI/R2 resection and a TT surgical approach were prognostic factors for poor OS. Conclusions： Improved perigastric lymph node dissection may be the main reason for better survival outcomes observed with a TA gastrectomy approach than with TT gastrectomy for Siewert III tumor patients.
基金supported by the National Natural Science Foundation of China(No.81802210)the Science&Technology Department of Sichuan Province(No.2021YFS0122)+1 种基金the Health Commission of Sichuan Province(No.20PJ056)the National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(No.Z2018B20).
文摘Background:Knee osteoarthritis(OA)is still challenging to prevent or treat.Enhanced endoplasmic reticulum(ER)stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration.This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms,which have rarely been reported.Methods:The expression of the histone methyltransferase enhancer of zeste homolog 2(EZH2),microRNA-142-3p(miR-142-3p),and high mobility group box 1(HMGB1)and the levels of ER stress,pyroptosis,and metabolic markers in normal and OA chondrocytes were investigated by western blotting,quantitative polymerase chain reaction,immunohistochemistry,fluorescence in situ hybridization,fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone(FAM-YVAD-FMK)/Hoechst 33342/propidium iodide(PI)staining,lactate dehydrogenase(LDH)release assays,and cell viability assessments.The effects of EZH2,miR-142-3p,and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation,luciferase reporters,gain/loss-of-function assays,and rescue assays in interleukin(IL)-1β-induced OA chondrocytes.The mechanistic contribution of EZH2,miR-142-3p,and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically,histologically,and immunohistochemically in surgically induced OA rats.Results:Increased EZH2 and HMGB1,decreased miR-142-3p,enhanced ER stress,and activated pyroptosis in chondrocytes were associated with OA occurrence and progression.EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes.EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation,and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3′-UTR of the HMGB1 gene.Moreover,ER stress mediated the effects of EZH2,miR-142-3p,and HMGB1 on chondrocyte pyroptosis.In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2,miR-142-3p,and HMGB1 and their effects on chondrocyte ER stress and pyroptosis.Conclusions:A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA,contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
