Objective:To investigate the effect of long-acting octreotide as adjuvant therapy in the prevention of tumor recurrence in patients with grade 2 pancreatic neuroendocrine tumors(pNETs)after radical resection.Methods:T...Objective:To investigate the effect of long-acting octreotide as adjuvant therapy in the prevention of tumor recurrence in patients with grade 2 pancreatic neuroendocrine tumors(pNETs)after radical resection.Methods:The postoperative follow-up data of 130 patients with resectable G2 pNET treated in the Changhai Hospital from 2008 to 2018 were retrospectively analyzed:59 patients received long-acting octreotide as adjuvant therapy for 6 to 12 months(Oct group)and 71 patients received active follow-up(control group),both of which began after the radical resection,with the primary observation endpoint of disease-free survival(DFS)and the secondary study endpoint of overall survival.Results:The median age of the patients in the Oct group and control group was 52 and 54 years,respectively.There were 28 male cases(47.5%)and 33 male cases(46.5%)in the 2 groups.The median maximum tumor diameter was 3.5 and 3.0 cm,respectively;lymph node metastasis was positive in 13 cases(22.0%)and 9 cases(12.7%);there was peripancreatic nerve invasion in 11 cases(18.6%)and 6 cases(8.5%).Survival analysis revealed that there were significant differences in 2-year DFS%(98.3%vs 88.7%,P=.0371)and 3-year DFS%(96.6%vs 85.9%,P=.0498)between the Oct group and control group.Long-acting octreotide treatment was found to reduce the risk of 3-year recurrence of G2 pNET after radical resection(HR=0.2,P=.044)with the application of inverse-probability-of-treatment weighted to balance the limited data bias.Conclusion:Using long-acting octreotide as adjuvant therapy for G2 pNET patients after radical surgery may improve the rate of 3y-DFS,but the benefit needs to be confirmed in a well-designed random control clinical trial.展开更多
Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport.For their clinical application,nanoliposomes must b...Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport.For their clinical application,nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects.Therefore,responsive drug-release strategies for inflammation treatment have been explored;however,no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation.Herein,we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes(R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate,RC-NL@DMF)that pre-cisely release encapsulated anti-pyroptotic drugs into pyroptotic cells.The activated key pyroptotic protein,the N-terminal domain of gasdermin E,selectively integrates with the cardiolipin of liposomes,thus forming pores for controlled drug release,pyroptosis,and inflammation inhibition.Therefore,RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice.Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery,suppressing pyroptosis and treating autoimmune inflammatory diseases.展开更多
Friction stir welding(FSW)was performed to produce Al/Ti lap joints under various welding conditions.More heat was generated when rotational rate increased or traversing rate decreased.Two types of Al/Ti interfaces–m...Friction stir welding(FSW)was performed to produce Al/Ti lap joints under various welding conditions.More heat was generated when rotational rate increased or traversing rate decreased.Two types of Al/Ti interfaces–mixed interface and diffusive interface–were formed under different welding conditions.The diffusive interface was formed with low heat input,and the mixed interface was formed more heat.The grains at the mixed interface were larger than those at the diffusive interface because of the higher heat input.Moreover,the microstructure of the mixed interface had a lower texture intensity compared with that of the diffusive interface,which was attributed to the enhanced continuous dynamic recrystallization(CDRX).TiAl3 was formed at the diffusive interface.When the interface varied to the mixed interface as heat input increased,TiAl was fomed within the Al/Ti mixture following the formation of TiAl3.In addition,TiAl3 precipitates were observed in the diffusion layer.The hardness value of the mixed interface was higher than 350 HV,due to the larger amount of intermetallic compounds(IMCs).The lap shear strength reached a maximum value of 147 MPa with medium heat input and an interface that exits in a critical state between diffusive and mixed interfaces.All the specimens fractured at the interface,which was attributed to the presence of IMCs.展开更多
Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied...Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied.The results showed that tryptase released after mast cell activation and degranulation plays a key role in visceral pain,and L.plantarum AR495 reduced the stimulation of colonic mast cells and the expression of protease-activated receptor 2(PAR2)and TRPV1 in dorsal root ganglia.Research further showed that supplementation with L.plantarum AR495 increased the level of short-chain fatty acids(SCFAs)and enhanced the barrier function of the colon.In addition,the microbiota analysis of the colon indicated that L.plantarum AR495 promoted the proliferation of Bifidobacterium and inhibited the proliferation of Lachnospiraceae,which alleviated the imbalance of the intestinal microbiota caused by IBS to a certain extent.In total,L.plantarum AR495 might reduce visceral sensitivity through the Mast cell-PAR2-TRPV1 signaling pathway by maintaining the homeostasis of the intestinal barrier.展开更多
文摘Objective:To investigate the effect of long-acting octreotide as adjuvant therapy in the prevention of tumor recurrence in patients with grade 2 pancreatic neuroendocrine tumors(pNETs)after radical resection.Methods:The postoperative follow-up data of 130 patients with resectable G2 pNET treated in the Changhai Hospital from 2008 to 2018 were retrospectively analyzed:59 patients received long-acting octreotide as adjuvant therapy for 6 to 12 months(Oct group)and 71 patients received active follow-up(control group),both of which began after the radical resection,with the primary observation endpoint of disease-free survival(DFS)and the secondary study endpoint of overall survival.Results:The median age of the patients in the Oct group and control group was 52 and 54 years,respectively.There were 28 male cases(47.5%)and 33 male cases(46.5%)in the 2 groups.The median maximum tumor diameter was 3.5 and 3.0 cm,respectively;lymph node metastasis was positive in 13 cases(22.0%)and 9 cases(12.7%);there was peripancreatic nerve invasion in 11 cases(18.6%)and 6 cases(8.5%).Survival analysis revealed that there were significant differences in 2-year DFS%(98.3%vs 88.7%,P=.0371)and 3-year DFS%(96.6%vs 85.9%,P=.0498)between the Oct group and control group.Long-acting octreotide treatment was found to reduce the risk of 3-year recurrence of G2 pNET after radical resection(HR=0.2,P=.044)with the application of inverse-probability-of-treatment weighted to balance the limited data bias.Conclusion:Using long-acting octreotide as adjuvant therapy for G2 pNET patients after radical surgery may improve the rate of 3y-DFS,but the benefit needs to be confirmed in a well-designed random control clinical trial.
基金sustained by the National Natural Science Foundation of China(82072512,52273152,22161132027)Zhejiang Provincial Natural Science Foundation of China(LY23H060013,LY21H070001,LY20H160044,LBY21H060003).
文摘Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport.For their clinical application,nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects.Therefore,responsive drug-release strategies for inflammation treatment have been explored;however,no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation.Herein,we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes(R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate,RC-NL@DMF)that pre-cisely release encapsulated anti-pyroptotic drugs into pyroptotic cells.The activated key pyroptotic protein,the N-terminal domain of gasdermin E,selectively integrates with the cardiolipin of liposomes,thus forming pores for controlled drug release,pyroptosis,and inflammation inhibition.Therefore,RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice.Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery,suppressing pyroptosis and treating autoimmune inflammatory diseases.
基金financial support of the project from Shandong Provincial Natural Science Foundation, China (No. ZR2016EEM43)
文摘Friction stir welding(FSW)was performed to produce Al/Ti lap joints under various welding conditions.More heat was generated when rotational rate increased or traversing rate decreased.Two types of Al/Ti interfaces–mixed interface and diffusive interface–were formed under different welding conditions.The diffusive interface was formed with low heat input,and the mixed interface was formed more heat.The grains at the mixed interface were larger than those at the diffusive interface because of the higher heat input.Moreover,the microstructure of the mixed interface had a lower texture intensity compared with that of the diffusive interface,which was attributed to the enhanced continuous dynamic recrystallization(CDRX).TiAl3 was formed at the diffusive interface.When the interface varied to the mixed interface as heat input increased,TiAl was fomed within the Al/Ti mixture following the formation of TiAl3.In addition,TiAl3 precipitates were observed in the diffusion layer.The hardness value of the mixed interface was higher than 350 HV,due to the larger amount of intermetallic compounds(IMCs).The lap shear strength reached a maximum value of 147 MPa with medium heat input and an interface that exits in a critical state between diffusive and mixed interfaces.All the specimens fractured at the interface,which was attributed to the presence of IMCs.
基金supported by the shanghai agriculture applied technology development program(2019-02-08-00-07-F01152)the national science fund for distinguished young scholars(32025029)+1 种基金the shanghai engineering research center of food microbiology program(19DZ2281100)the national key R&D program of china(2018YFC1604305)。
文摘Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied.The results showed that tryptase released after mast cell activation and degranulation plays a key role in visceral pain,and L.plantarum AR495 reduced the stimulation of colonic mast cells and the expression of protease-activated receptor 2(PAR2)and TRPV1 in dorsal root ganglia.Research further showed that supplementation with L.plantarum AR495 increased the level of short-chain fatty acids(SCFAs)and enhanced the barrier function of the colon.In addition,the microbiota analysis of the colon indicated that L.plantarum AR495 promoted the proliferation of Bifidobacterium and inhibited the proliferation of Lachnospiraceae,which alleviated the imbalance of the intestinal microbiota caused by IBS to a certain extent.In total,L.plantarum AR495 might reduce visceral sensitivity through the Mast cell-PAR2-TRPV1 signaling pathway by maintaining the homeostasis of the intestinal barrier.
