The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the tre...The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.展开更多
To investigate the fatty acid-based functional lipidomics of patients on long-term home parenteral nutrition receiving different intravenous lipid emulsions.METHODSA cross-sectional comparative study was carried out o...To investigate the fatty acid-based functional lipidomics of patients on long-term home parenteral nutrition receiving different intravenous lipid emulsions.METHODSA cross-sectional comparative study was carried out on 3 groups of adults on home parenteral nutrition(HPN),receiving an HPN admixture containing an olive-soybean oil-based intravenous lipid emulsion(IVLE)(OO-IVLE;n=15),a soybean-medium-chain triacylglycerol-olive-fish oil-based IVLE(SMOF-IVLE;n=8)or HPN without IVLE(No-IVLE;n=8)and 42 healthy controls(HCs).The inclusion criteria were:duration of HPN≥3 mo,current HPN admixtures≥2 mo and HPN infusions≥2/wk.Blood samples were drawn 4-6 h after the discontinuation of the overnight HPN infusion.The functional lipidomics panel included:the red blood cell(RBC)fatty acid(FA)profile,molecular biomarkers[membrane fluidity:saturated/monounsaturated FA ratio=saturated fatty acid(SFA)/monounsaturated fatty acid(MUFA)index;inflammatory risk:n-6/n-3 polyunsaturated fatty acid(PUFA)ratio=n-6/n-3 index;cardiovascular risk:sum of n-3 eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)=n-3 index;free radical stress:sum of FA trans isomers=%trans index]and FA pathway enzyme activity estimate(delta-9-desaturase=D9D;delta-6-desaturase=D6D;delta-5-desaturase=D5D;elongase=ELO).Statistics were carried out using nonparametric tests.The amount of each FA was calculated as a percentage of the total FA content(relative%).RESULTSIn the OO-IVLE group,the percentage of oleic acid in the RBCs was positively correlated with the weekly load of OO-IVLE(r=0.540,P=0.043).In the SMOF-IVLE cohort,the RBC membrane EPA and DHA were positively correlated with the daily amount of SMOF-IVLE(r=0.751,P=0.044)and the number of HPN infusions per week(r=0.753;P=0.046),respectively.The SMOF-IVLE group showed the highest EPA and DHA and the lowest arachidonic acid percentages(P<0.001).The RBC membrane linoleic acid content was lower,and oleic and vaccenic acids were higher in all the HPN groups in comparison to the HCs.Vaccenic acid was positively correlated with the weekly HPN load of glucose in both the OO-IVLE(r=0.716;P=0.007)and the SMOF-IVLE(r=0.732;P=0.053)groups.The estimated activity of D9D was higher in all the HPN groups than in the HCs(P<0.001).The estimated activity of D5D was lower in the SMOF-IVLE group than in the HCs(P=0.013).The SFA/MUFA ratio was lower in all the HPN groups than in the HCs(P<0.001).The n-6/n-3 index was lower and the n-3 index was higher in the SMOF-IVLE group in comparison to the HCs and to the other HPN groups(P<0.001).The%trans index did not differ among the four groups.CONCLUSIONThe FA profile of IVLEs significantly influenced the cell membrane functional lipidomics.The amount of glucose in the HPN may play a relevant role,mediated by the insulin regulation of the FA pathway enzyme activities.展开更多
Background The aim of this study was to assess whether the autologous internal iliac artery and vein could be used as an interpositional graft for vascular reconstruction in segmental intestinal allografts and autogra...Background The aim of this study was to assess whether the autologous internal iliac artery and vein could be used as an interpositional graft for vascular reconstruction in segmental intestinal allografts and autografts.Methods Thirty-four intestinal transplants(19 living-related allografts and 15 autografts)were conducted in our programs between January 2011 and January 2019.Patient characteristics,type of vascular reconstruction,and post-operative complications were reviewed.Results There were 20 males and 14 females with a median age of 35 years.Of 34 grafts,22(64.7%)(11 allografts and 11 autografts)were revascularized using the autologous internal iliac artery and vein for reconstruction.Vascular reconstruction on the back table took 2166min to complete.Both total operative time and cold ischemia time tended to be longer in the vascular-reconstruction group than in the direct-anastomosis group(5306226 vs 4406116 and 159649 vs 125666 min,respectively),but these differences were not significant.The incidence of vascular thrombosis tended to be higher in the direct-anastomosis group than in the vascular-reconstruction group(16.7%vs 0%,P=0.118).At a median follow-up of 36.9 months,no stenosis or pseudoaneurysms developed.In 19 allografts,acute rejection occurred in 4(21.1%)and chronic rejection occurred in 1(5.2%).Conclusions Our results indicate that the use of an autologous internal iliac interposition graft greatly facilitates intestinal graft implantation and minimizes the risk of vascular complications.展开更多
文摘The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.
文摘To investigate the fatty acid-based functional lipidomics of patients on long-term home parenteral nutrition receiving different intravenous lipid emulsions.METHODSA cross-sectional comparative study was carried out on 3 groups of adults on home parenteral nutrition(HPN),receiving an HPN admixture containing an olive-soybean oil-based intravenous lipid emulsion(IVLE)(OO-IVLE;n=15),a soybean-medium-chain triacylglycerol-olive-fish oil-based IVLE(SMOF-IVLE;n=8)or HPN without IVLE(No-IVLE;n=8)and 42 healthy controls(HCs).The inclusion criteria were:duration of HPN≥3 mo,current HPN admixtures≥2 mo and HPN infusions≥2/wk.Blood samples were drawn 4-6 h after the discontinuation of the overnight HPN infusion.The functional lipidomics panel included:the red blood cell(RBC)fatty acid(FA)profile,molecular biomarkers[membrane fluidity:saturated/monounsaturated FA ratio=saturated fatty acid(SFA)/monounsaturated fatty acid(MUFA)index;inflammatory risk:n-6/n-3 polyunsaturated fatty acid(PUFA)ratio=n-6/n-3 index;cardiovascular risk:sum of n-3 eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)=n-3 index;free radical stress:sum of FA trans isomers=%trans index]and FA pathway enzyme activity estimate(delta-9-desaturase=D9D;delta-6-desaturase=D6D;delta-5-desaturase=D5D;elongase=ELO).Statistics were carried out using nonparametric tests.The amount of each FA was calculated as a percentage of the total FA content(relative%).RESULTSIn the OO-IVLE group,the percentage of oleic acid in the RBCs was positively correlated with the weekly load of OO-IVLE(r=0.540,P=0.043).In the SMOF-IVLE cohort,the RBC membrane EPA and DHA were positively correlated with the daily amount of SMOF-IVLE(r=0.751,P=0.044)and the number of HPN infusions per week(r=0.753;P=0.046),respectively.The SMOF-IVLE group showed the highest EPA and DHA and the lowest arachidonic acid percentages(P<0.001).The RBC membrane linoleic acid content was lower,and oleic and vaccenic acids were higher in all the HPN groups in comparison to the HCs.Vaccenic acid was positively correlated with the weekly HPN load of glucose in both the OO-IVLE(r=0.716;P=0.007)and the SMOF-IVLE(r=0.732;P=0.053)groups.The estimated activity of D9D was higher in all the HPN groups than in the HCs(P<0.001).The estimated activity of D5D was lower in the SMOF-IVLE group than in the HCs(P=0.013).The SFA/MUFA ratio was lower in all the HPN groups than in the HCs(P<0.001).The n-6/n-3 index was lower and the n-3 index was higher in the SMOF-IVLE group in comparison to the HCs and to the other HPN groups(P<0.001).The%trans index did not differ among the four groups.CONCLUSIONThe FA profile of IVLEs significantly influenced the cell membrane functional lipidomics.The amount of glucose in the HPN may play a relevant role,mediated by the insulin regulation of the FA pathway enzyme activities.
基金supported by the grant from the National Natural Science Foundation of China[#81770644]Key Program of National Natural Science Foundation of Zhejiang Province(LD21H03000).
文摘Background The aim of this study was to assess whether the autologous internal iliac artery and vein could be used as an interpositional graft for vascular reconstruction in segmental intestinal allografts and autografts.Methods Thirty-four intestinal transplants(19 living-related allografts and 15 autografts)were conducted in our programs between January 2011 and January 2019.Patient characteristics,type of vascular reconstruction,and post-operative complications were reviewed.Results There were 20 males and 14 females with a median age of 35 years.Of 34 grafts,22(64.7%)(11 allografts and 11 autografts)were revascularized using the autologous internal iliac artery and vein for reconstruction.Vascular reconstruction on the back table took 2166min to complete.Both total operative time and cold ischemia time tended to be longer in the vascular-reconstruction group than in the direct-anastomosis group(5306226 vs 4406116 and 159649 vs 125666 min,respectively),but these differences were not significant.The incidence of vascular thrombosis tended to be higher in the direct-anastomosis group than in the vascular-reconstruction group(16.7%vs 0%,P=0.118).At a median follow-up of 36.9 months,no stenosis or pseudoaneurysms developed.In 19 allografts,acute rejection occurred in 4(21.1%)and chronic rejection occurred in 1(5.2%).Conclusions Our results indicate that the use of an autologous internal iliac interposition graft greatly facilitates intestinal graft implantation and minimizes the risk of vascular complications.
