Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are dr...Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.展开更多
We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of ne...We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.展开更多
Objective: To evaluate the efficacy and short term prognosis of Tirofiban in different treatment duration in patients with acute ST segment elevation myocardial infarction (STEMI) and percutaneous coronary interventio...Objective: To evaluate the efficacy and short term prognosis of Tirofiban in different treatment duration in patients with acute ST segment elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI) combined with intracoronary injection. Methods: A total of 125 patients with acute STEMI were enrolled in this study. They were randomly divided into two groups: control group (n ? 61) and Tirofiban group (n ? 64). The Tirofiban was used by intracoronary and intravenous administration in Tirofiban group which was randomly divided into three sub-groups according to the duration of Tirofiban by persistent intravenous injection for 12 hours, 24 hours or 36 hours. Thrombolysis in myocardial infarction flow and myocardial perfusion grades were recorded immediately after PCI. The adverse cardiac events and cardiac death within 180 days of PCI, and the adverse effects (hemorrhage and thrombocytopenia) were compared between the two groups and within Tirofiban sub-groups. Results: Grade 3 in myocardial perfusion was significantly better in Tirofiban group than control group (85.94% vs. 72.13%, P ? 0.03) after PCI. There was one cardiac death in control group in 180 days after PCI. The adverse cardiac event rates between two groups was significant difference (16 patients in control group and only 8 in Tirofiban group, P ? 0.047). There was no significant difference in incidence of hemorrhage complications and platelet counts between two groups. Nevertheless, hemorrhage complications in the 12-and 24-hour subgroups were less than 36-hour subgroup (P ? 0.01). Conclusions: Intravenous Tirofiban treatment reduced the adverse cardiac events and improved short term prognosis without increasing the adverse reactions of the drugs in patients undergoing PCI. The less rate of hemorrhage complication can be achieved in short-duration of Tirofiban by intravenous injection after PCI. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communication展开更多
A series of arylsulfonamide and arylamide derivatives have been prepared from anisole in good yields. The structures of those compounds were confirmed by 1H-NMR and MS analysis. Their activities against platelet aggre...A series of arylsulfonamide and arylamide derivatives have been prepared from anisole in good yields. The structures of those compounds were confirmed by 1H-NMR and MS analysis. Their activities against platelet aggregation were tested in vitro by using the Born test on rabbits.展开更多
The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits we...The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.展开更多
Decorsin, an antagonist of integrin glycoprotein IIb/IIIa, contains Arg-Gly-Asp （RGD） sequence and three disulfide bridges. The function of RGD sequence has already been well defined, but the roles of conserved disu...Decorsin, an antagonist of integrin glycoprotein IIb/IIIa, contains Arg-Gly-Asp （RGD） sequence and three disulfide bridges. The function of RGD sequence has already been well defined, but the roles of conserved disulfide bonds in antihemostatic proteins still remain unclear. Herein we use the fusion expression and characterization of mutant decorsin to study the func- tions of disulfide bonds in protein structure, stability and biological activity. The purified protein shows an apparent inhibition of activity to platelet aggregation induced by ADP with IC50 of 500 nM. The removal of cys7-cysl5 （from cysteine to serine） at the N-terminal causes a thirty-fold decrease of the inhibition activity with IC50 of 15 ~tM, whereas the mutation of cys22-cys38 at the C-terminal completely impairs the biological activity of decorsin. The overall secondary and tertiary struc- tures of decorsin are disrupted inevitably without disulfide bonds. Using a domain insertion mutation, the retaining of RGD loop and the adjacent disulfide bond produces a week antihemostatic activity of decorsin. This reveals that the overall structure of decorsin stabilized by the three conserved disulfide bridges is cooperative for antihemostatic function. Our study on the ef- fect of disulfide bonds together with RGD-sequence on the protein function is helpful for structure-based drug design of an- tithrombotic research.展开更多
AIM： To study the secretory inhibitor of platelet microbicidal protein （SIPMP） phenotypes of faecal anaerobic isolates from patients with diarrhea.METHODS： Faecal isolates of anaerobic bacteria （B. fragilis, n = ...AIM： To study the secretory inhibitor of platelet microbicidal protein （SIPMP） phenotypes of faecal anaerobic isolates from patients with diarrhea.METHODS： Faecal isolates of anaerobic bacteria （B. fragilis, n = 42; B. longum, n = 70; A. israelii, n = 21; E. lentum, n = 12） from children with diarrhea were tested. SIPMP production was tested by inhibition of platelet microbicidal protein （PMP） bioactivity against B. subtilis and was expressed as percentage of inhibition of PMP bactericidal activity.RESULTS： Among anaerobic isolates 80% of B. longum strains, 85.7% of A. israeli/strains, 50% of E. lentum strains and 92.86% of B. fragilis strains were SIPMP-positive. The isolated anaerobic organisms demonstrated SIPMP production at a mean level of 13.8% ± 0.7%, 14.7% ± 1.8%, 3.9% ± 0.9% （P 〈 0.05） and 26.8% ± 7.5% （P 〈 0.05） for bifidobacteria, A. israelii, E. lentum and B. fragilis, respectively.CONCLUSION： Data from the present study may have significant implications in understanding the pathogenesis of microecological disorders in the intestine, as well as for future improvement in the prevention and therapy of anaerobe-associated infections.展开更多
文摘Gastrointestinal stromal tumors(GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest,especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene,BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential,and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure,targeted therapy in the form of tyrosine kinase inhibitors(TKIs) has revolutionized the management options. As the first-line TKI,imatinib offers treatment for advanced and metastatic GISTs,adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options,including prolonging the first-line TKI from 1 to 3 years,increasing the dose of TKI or switching to second-line TKI. Other newer TKIs,such as sunitinib and regorafenib,may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated,such as inhibitors of BRAF,heat shock protein 90,glutamine and mitogenactivated protein kinase signaling,as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe,North America and Asia are highlighted.
文摘We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.
文摘Objective: To evaluate the efficacy and short term prognosis of Tirofiban in different treatment duration in patients with acute ST segment elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI) combined with intracoronary injection. Methods: A total of 125 patients with acute STEMI were enrolled in this study. They were randomly divided into two groups: control group (n ? 61) and Tirofiban group (n ? 64). The Tirofiban was used by intracoronary and intravenous administration in Tirofiban group which was randomly divided into three sub-groups according to the duration of Tirofiban by persistent intravenous injection for 12 hours, 24 hours or 36 hours. Thrombolysis in myocardial infarction flow and myocardial perfusion grades were recorded immediately after PCI. The adverse cardiac events and cardiac death within 180 days of PCI, and the adverse effects (hemorrhage and thrombocytopenia) were compared between the two groups and within Tirofiban sub-groups. Results: Grade 3 in myocardial perfusion was significantly better in Tirofiban group than control group (85.94% vs. 72.13%, P ? 0.03) after PCI. There was one cardiac death in control group in 180 days after PCI. The adverse cardiac event rates between two groups was significant difference (16 patients in control group and only 8 in Tirofiban group, P ? 0.047). There was no significant difference in incidence of hemorrhage complications and platelet counts between two groups. Nevertheless, hemorrhage complications in the 12-and 24-hour subgroups were less than 36-hour subgroup (P ? 0.01). Conclusions: Intravenous Tirofiban treatment reduced the adverse cardiac events and improved short term prognosis without increasing the adverse reactions of the drugs in patients undergoing PCI. The less rate of hemorrhage complication can be achieved in short-duration of Tirofiban by intravenous injection after PCI. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communication
基金KZ acknowledges supports from the National Young Scholar Award of the NSFC(#30125043)from the Chung Kong Scholars Program administered by the Ministry of Education,PRC and the Li Ka Shing Foundation,Hong Kong.
文摘A series of arylsulfonamide and arylamide derivatives have been prepared from anisole in good yields. The structures of those compounds were confirmed by 1H-NMR and MS analysis. Their activities against platelet aggregation were tested in vitro by using the Born test on rabbits.
文摘The regulatory effects of phospholipase A2(PLA2) inhibitors, chloroquine and dexamethasone, on the activity of blood PLA2 and its related lipid mediators during endotoxic shock were observed in rabbits. The rabbits were randomized into 4 groups as follows : The normal control (NC) group consisted of 12 rabbits with sham injection . the endotoxic shork (ES) group of 31 rabbits, the chloquine pretreated (CQ) group of 16 rabbits receiving 3 mg/kg of chlorqouine and the dexamethasone-pretreated (DM) group of 10 rabbits receiving 5 mg/kg of dexamethasone. Blood was sampled before and 5 and 30 min, 1 ,3, 5 and 8 h after the administration of endotoxin for the determination of PLA2, platelet activating factor (PAF) , TXB2 and 6-keto-PGF1α. In addrtion, changes of mean arterial pressure (MAP) and respiratory rate (RR) were also carefully recorded. It was found that the activities of PLA2 and PAF and the levels of TXB2 and 6-keto-PGF1α. were significantly increased after the infusion of endotoxin. CQ and DM markedly suppressed the activities of PLA2 and PAF. The inhibition of CQ on TXB2 and 6-keto-PGF1α was greater than that of DM. Besides, CQ and DM could increase the survival rate of the animals from 48% to 75% (CQ group) and 70% (DM group). These findings suggest that PLA2 inhibitors such as CQ and DM can significantly attenuate the formation of shock mediators such as PLA2, PAF, TXB2 and 6-keto-PGF1α, and so improve the prognosis of the victims of endotoxic shock.
基金supported by the National Natural Science Foundation of China(91127026,11074115 and 61101056)the Open Project of State Key Laboratory of Bioelectronics of Southeast University(2011E14)supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Decorsin, an antagonist of integrin glycoprotein IIb/IIIa, contains Arg-Gly-Asp （RGD） sequence and three disulfide bridges. The function of RGD sequence has already been well defined, but the roles of conserved disulfide bonds in antihemostatic proteins still remain unclear. Herein we use the fusion expression and characterization of mutant decorsin to study the func- tions of disulfide bonds in protein structure, stability and biological activity. The purified protein shows an apparent inhibition of activity to platelet aggregation induced by ADP with IC50 of 500 nM. The removal of cys7-cysl5 （from cysteine to serine） at the N-terminal causes a thirty-fold decrease of the inhibition activity with IC50 of 15 ~tM, whereas the mutation of cys22-cys38 at the C-terminal completely impairs the biological activity of decorsin. The overall secondary and tertiary struc- tures of decorsin are disrupted inevitably without disulfide bonds. Using a domain insertion mutation, the retaining of RGD loop and the adjacent disulfide bond produces a week antihemostatic activity of decorsin. This reveals that the overall structure of decorsin stabilized by the three conserved disulfide bridges is cooperative for antihemostatic function. Our study on the ef- fect of disulfide bonds together with RGD-sequence on the protein function is helpful for structure-based drug design of an- tithrombotic research.
基金The Russian Foundation of Basic Research and Government of Orenburg region, No. 07-04-97624 and No. 08-04-99105
文摘AIM： To study the secretory inhibitor of platelet microbicidal protein （SIPMP） phenotypes of faecal anaerobic isolates from patients with diarrhea.METHODS： Faecal isolates of anaerobic bacteria （B. fragilis, n = 42; B. longum, n = 70; A. israelii, n = 21; E. lentum, n = 12） from children with diarrhea were tested. SIPMP production was tested by inhibition of platelet microbicidal protein （PMP） bioactivity against B. subtilis and was expressed as percentage of inhibition of PMP bactericidal activity.RESULTS： Among anaerobic isolates 80% of B. longum strains, 85.7% of A. israeli/strains, 50% of E. lentum strains and 92.86% of B. fragilis strains were SIPMP-positive. The isolated anaerobic organisms demonstrated SIPMP production at a mean level of 13.8% ± 0.7%, 14.7% ± 1.8%, 3.9% ± 0.9% （P 〈 0.05） and 26.8% ± 7.5% （P 〈 0.05） for bifidobacteria, A. israelii, E. lentum and B. fragilis, respectively.CONCLUSION： Data from the present study may have significant implications in understanding the pathogenesis of microecological disorders in the intestine, as well as for future improvement in the prevention and therapy of anaerobe-associated infections.
