Background Quantitative flow ratio(QFR)based lesion selection for percutaneous coronary intervention(PCI)treatment has shown clinical benefits in terms of reduced risk for myocardial infarction and repeat revasculariz...Background Quantitative flow ratio(QFR)based lesion selection for percutaneous coronary intervention(PCI)treatment has shown clinical benefits in terms of reduced risk for myocardial infarction and repeat revascularization.Whether this benefit is consistent across different age groups still needs further investigation.Methods In this prespecified subgroup study of FAVORⅢChina trial,we compared long-term clinical outcomes between QFR-guided and angiography-guided PCI among different age groups among 3825 enrolled subjects.The primary endpoint was major adverse cardiac events(MACEs),a composite of all-cause death,myocardial infarction,and ischemia-driven revascularization.Results Of the 3825 patients,1717(44.9%)were aged≥65 years.At baseline,patients≥65 had higher rates of hypertension,hyperlipidaemia,stroke history(P<0.0001),and peripheral vascular disease(P=0.024)and had higher SYNTAX scores(P=0.0095).Compared with standard angiography guidance,the QFR-guided strategy consistently reduced the 1-year(≥65 years,6.04%vs.9.19%,HR=0.65,95%CI:0.46–0.92;<65 years,5.53%vs.8.43%,HR=0.65,95%CI:0.47–0.91)and 3-year MACE rates in both age groups(≥65 years,11.8%vs.15.2%,HR:0.75,95%CI:0.58–0.98;<65 years,9.5%vs.14.6%,HR=0.63;95%CI:0.49–0.81),without a significant interaction(Pinteraction=0.99).Within the QFR-guided group,the 3-year MACE rate in patients with deferred vessels was numerically greater in patients aged≥65 years than in those aged<65 years(8.3%vs.3.0%,P=0.10).Conclusions Although with higher rate of comorbidities and more complex coronary anatomy,the long-term benefit of the QFR-guided PCI strategy remained consistent in patients≥65 years,compared with those<65 years.展开更多
Kounis syndrome(KS)is a rare but clinically significant condition characterized by the simultaneous occurrence of acute coronary syndrome(ACS)and allergic reactions,which can develop in patients with either normal or ...Kounis syndrome(KS)is a rare but clinically significant condition characterized by the simultaneous occurrence of acute coronary syndrome(ACS)and allergic reactions,which can develop in patients with either normal or diseased coronary arteries.[1,2]The condition is typically triggered by various allergens including medications(particularly contrast media),environmental factors,or food exposures,with symptom onset usually occurring within one hour of exposure.展开更多
Ti_(2)AlC/TiAl composites with a network structure were successfully prepared with carbon nanotubes and Ti-45Al-8Nb pre-alloyed powder using spark plasma sintering.The effects of sintering temperature(1200-1350℃)on t...Ti_(2)AlC/TiAl composites with a network structure were successfully prepared with carbon nanotubes and Ti-45Al-8Nb pre-alloyed powder using spark plasma sintering.The effects of sintering temperature(1200-1350℃)on the microstructural evolution and mechanical properties were systematically investigated.The microstructure of Ti_(2)AlC/TiAl composites exhibits duplex,near-lamellar,and fully lamellar structures,as the sintering temperature increases from 1200 to 1350℃.The network structured Ti_(2)AlC phase can refine the microstructure and the phase becomes discontinuous at high sintering temperatures.Notably,composites sintered at 1300℃ exhibit excellent mechanical properties,with the highest compressive strength(1921 MPa)and fracture strain(26%)at room temperature.Moreover,the ultimate tensile strength and fracture strain reach 537 MPa and 3.1%at 900℃,and 485 MPa and 3.3%at 950℃,respectively.The enhancement of the mechanical properties is attributed primarily to the load bearing,particle pull-out,and inhibition of crack propagation induced by Ti_(2)AlC particles.展开更多
BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the u...BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous(IO) access and central venous catheterization(CVC) in critically ill Chinese patients.METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above.RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group(91.7% vs. 50.0%, P<0.001;52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion(1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups.CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.展开更多
BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST w...BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention(PCI).Patients from ten Chinese hospitals diagnosed as stent thrombosis(ST)from January 2010 to December 2016 were retrospectively included as the study group.A control group(1 case:2 controls)was created by including patients without ST,major adverse cardiovascular events,or cerebrovascular events during follow-up.The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients,who were included to identify factors that predicted EST and to develop a prediction scoring system.The other 171 patients without integrated 1:2 pair were used for external validation.RESULTS:EST was independently associated with a low hemoglobin concentration(adjusted odds ratio[OR]0.946,95%confi dence interval[95%CI]0.901-0.993,P=0.026),a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score(OR 1.166,95%CI 1.049-1.297,P=0.004),and a DAPT(DAPT)duration of<30 days(OR 28.033,95%CI 5.302-272.834,P<0.001).The simple EST prediction score provided an area under the curve(AUC)of 0.854(95%CI 0.777-0.932,P<0.001)with 70.0%sensitivity and 90.0%specifi city,and 0.742(95%CI 0.649-0.835,P<0.001)with 54.5%sensitivity and 81.0%specifi city for external validation dataset.CONCLUSIONS:EST may be independently associated with DAPT discontinuation within 30 days,a low hemoglobin concentration,and a high SYNTAX score.The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.展开更多
BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclea...BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.展开更多
The in-situ micro-nano Ti_(2)AlC particles reinforced TiAl(Ti_(2)AlC/TiAl)composite was fabricated using spark plasma sintering.The hot workability of Ti_(2)AlC/TiAl composite was studied,and the effect of micro-nano ...The in-situ micro-nano Ti_(2)AlC particles reinforced TiAl(Ti_(2)AlC/TiAl)composite was fabricated using spark plasma sintering.The hot workability of Ti_(2)AlC/TiAl composite was studied,and the effect of micro-nano particles on flow stress and dynamic recrystallization of composite was discussed.The results showed that the micro-nano Ti_(2)AlC particles included strengthening and softening effects during hot deformation,resulting in the fact that the Ti_(2)AlC/TiAl composite exhibited a higher flow stress and more sufficient dynamic recrystallization.The strengthening effect was mainly attributed to the Ti_(2)AlC particles induced refinement strengthening and hindered dislocation motion at the initial stage.Moreover,the precipitation of nano-TiCr2 particles induced by stress concentration during hot deformation also contributed to higher flow stress via impeding dislocation motion.Meanwhile,the refined microstructure and dislocation pile-up caused by micro-nano particles during deformation provided more nucleation sites for dynamic recrystallization,which significantly promoted the dynamic recrystallization of the second stage.The present results reveal that the Ti_(2)AlC/TiAl composite exhibited excellent hot workability,which is important to promote the application of TiAl alloys.展开更多
F-652 is a recombinant fusion protein consisting of two human interleukin-22(IL-22)molecules linked to an immunoglobulin constant region(IgG 2-Fc).IL-22 plays critical roles in promoting tissue repair and suppressing ...F-652 is a recombinant fusion protein consisting of two human interleukin-22(IL-22)molecules linked to an immunoglobulin constant region(IgG 2-Fc).IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection.The safety,pharmacokinetics(PK),tolerability,and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized,double-blind,placebo-controlled study.Following single-dose subcutaneous(SC)injection of F-652 at 2.0µg/kg into healthy subjects,six out of six subjects experienced delayed injection site reactions,which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing.F-652 was then administered to the healthy subjects via an intravenous(IV)infusion at 2.0,10,30,and 45µg/kg.No severe adverse event(SAE)was observed during the study.Among the IV-dosed cohorts,eye and skin treatment emergent adverse events(TEAEs)were observed in the 30 and 45µg/kg cohorts.F-652 IV dosing resulted in linear increases in C max and AUC(0–t),and the T 1/2 ranged from 39.4 to 206h in the cohorts.An IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A,C-reactive protein,and FIB,and decreased serum triglycerides.The serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45μg/kg.In conclusion,IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic properties.These results warrant further clinical development of F-652 to treat inflammatory diseases.展开更多
Background and Aims:The overall survival(OS)of hepatocellular carcinoma(HCC)remains dismal.Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical decision.This st...Background and Aims:The overall survival(OS)of hepatocellular carcinoma(HCC)remains dismal.Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical decision.This study aimed to develop a prognostic gene model for HCC.Methods:GSE14520 was retrieved as a training set to identify differential expressed genes(DEGs)between tumor and adjacent liver tissues in HCC patients with different OS.A DEG-based prognostic model was then constructed and the TCGA-LIHC and ICGC-LIRI datasets were used to validate the model.The area under the receiver operating characteristic curve(AUC)and hazard ratio(HR)of the model for OS were calculated.A model-based nomogram was estab-lished and verified.Results:In the training set,differential expression analysis identified 80 genes dysregulated in oxidation-reduction and metabolism regulation.After univariate Cox and LASSO regression,eight genes(LPCAT1,DHRS1,SORBS2,ALDH5A1,SULT1C2,SPP1,HEY1 and GOLM1)were selected to build the prognostic model.The AUC for 1-,3-and 5-year OS were 0.779,0.736,0.754 in training set and 0.693,0.689,0.693 in the TCGA-LIHC validation set,respectively.The AUC for 1-and 3-year OS were 0.767 and 0.705 in the ICGC-LIRI validation set.Multivariate analysis confirmed the model was an independent prognostic factor(training set:HR=4.422,p<0.001;TCGA-LIHC validation set:HR=2.561,p<0.001;ICGC-LIRI validation set:HR=3.931,p<0.001).Furthermore,a nomogram combining the model and AJCC stage was established and validated,showing increased OS predictive efficacy compared with the prognostic model(p=0.035)or AJCC stage(p<0.001).Conclusions:Our eight-gene prognostic model and the related nomogram represent as reliable prognostic tools for OS prediction in HCC patients.展开更多
文摘Background Quantitative flow ratio(QFR)based lesion selection for percutaneous coronary intervention(PCI)treatment has shown clinical benefits in terms of reduced risk for myocardial infarction and repeat revascularization.Whether this benefit is consistent across different age groups still needs further investigation.Methods In this prespecified subgroup study of FAVORⅢChina trial,we compared long-term clinical outcomes between QFR-guided and angiography-guided PCI among different age groups among 3825 enrolled subjects.The primary endpoint was major adverse cardiac events(MACEs),a composite of all-cause death,myocardial infarction,and ischemia-driven revascularization.Results Of the 3825 patients,1717(44.9%)were aged≥65 years.At baseline,patients≥65 had higher rates of hypertension,hyperlipidaemia,stroke history(P<0.0001),and peripheral vascular disease(P=0.024)and had higher SYNTAX scores(P=0.0095).Compared with standard angiography guidance,the QFR-guided strategy consistently reduced the 1-year(≥65 years,6.04%vs.9.19%,HR=0.65,95%CI:0.46–0.92;<65 years,5.53%vs.8.43%,HR=0.65,95%CI:0.47–0.91)and 3-year MACE rates in both age groups(≥65 years,11.8%vs.15.2%,HR:0.75,95%CI:0.58–0.98;<65 years,9.5%vs.14.6%,HR=0.63;95%CI:0.49–0.81),without a significant interaction(Pinteraction=0.99).Within the QFR-guided group,the 3-year MACE rate in patients with deferred vessels was numerically greater in patients aged≥65 years than in those aged<65 years(8.3%vs.3.0%,P=0.10).Conclusions Although with higher rate of comorbidities and more complex coronary anatomy,the long-term benefit of the QFR-guided PCI strategy remained consistent in patients≥65 years,compared with those<65 years.
基金supported by the National Key Research and Development Program of China(No.2022YFB380-7300)the National Natural Science Foundation of China(No.12471455)+2 种基金the Clinical Cohort Construction Program of Peking University Third Hospital(BYSYDL2022005)the Key Clinical Projects of Peking University Third Hospital(BYSYZD2023006)the Innovation&Transfer Fund of Peking University Third Hospital(BYSYZHKC2023-109).
文摘Kounis syndrome(KS)is a rare but clinically significant condition characterized by the simultaneous occurrence of acute coronary syndrome(ACS)and allergic reactions,which can develop in patients with either normal or diseased coronary arteries.[1,2]The condition is typically triggered by various allergens including medications(particularly contrast media),environmental factors,or food exposures,with symptom onset usually occurring within one hour of exposure.
基金financially supported by the National Natural Science Foundation of China(Nos.52171120,52271106,52071188)the Natural Science Foundation of Zhejiang Province,China(No.LZY23E050001)。
文摘Ti_(2)AlC/TiAl composites with a network structure were successfully prepared with carbon nanotubes and Ti-45Al-8Nb pre-alloyed powder using spark plasma sintering.The effects of sintering temperature(1200-1350℃)on the microstructural evolution and mechanical properties were systematically investigated.The microstructure of Ti_(2)AlC/TiAl composites exhibits duplex,near-lamellar,and fully lamellar structures,as the sintering temperature increases from 1200 to 1350℃.The network structured Ti_(2)AlC phase can refine the microstructure and the phase becomes discontinuous at high sintering temperatures.Notably,composites sintered at 1300℃ exhibit excellent mechanical properties,with the highest compressive strength(1921 MPa)and fracture strain(26%)at room temperature.Moreover,the ultimate tensile strength and fracture strain reach 537 MPa and 3.1%at 900℃,and 485 MPa and 3.3%at 950℃,respectively.The enhancement of the mechanical properties is attributed primarily to the load bearing,particle pull-out,and inhibition of crack propagation induced by Ti_(2)AlC particles.
基金supported by the Capital Clinical Characteristic Applied Research Project(z151100004015118)the Fostering and Exploring Project of Key Clinical Projects in the Peking University Third Hospital(BYSY2014006)the Health Science Promotion Project of Beijing(TG-2017-83)。
文摘BACKGROUND: It is challenging to establish peripheral intravenous access in adult critically patients. This study aims to compare the success rate of the first attempt, procedure time, operator satisfaction with the used devices, pain score, and complications between intraosseous(IO) access and central venous catheterization(CVC) in critically ill Chinese patients.METHODS: In this prospective clustered randomized controlled trial, eight hospitals were randomly divided into either the IO group or the CVC group. Patients who needed emergency vascular access were included. From April 1, 2017 to December 31, 2018, each center included 12 patients. We recorded the data mentioned above.RESULTS: A total of 96 patients were enrolled in the study. There were no statistically significant differences between the two groups regarding sex, age, body mass index, or operator satisfaction with the used devices. The success rates of the first attempt and the procedure time were statistically significant between the IO group and the CVC group(91.7% vs. 50.0%, P<0.001;52.0 seconds vs. 900.0 seconds, P<0.001). During the study, 32 patients were conscious. There was no statistically significant difference between the two groups regarding the pain score associated with insertion. There were statistically significant differences between the two groups regarding the pain score associated with IO or CVC infusion(1.5 vs. 0.0, P=0.044). Complications were not observed in the two groups.CONCLUSIONS: IO access is a safe, rapid, and effective technique for gaining vascular access in critically ill adults with inaccessible peripheral veins in the emergency departments.
基金from National Key R&D Program of China(2016YFC1301300,2016YFC1301302)。
文摘BACKGROUND:The predictive scoring systems for early stent thrombosis(EST)remains blank in China.The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population.METHODS:EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention(PCI).Patients from ten Chinese hospitals diagnosed as stent thrombosis(ST)from January 2010 to December 2016 were retrospectively included as the study group.A control group(1 case:2 controls)was created by including patients without ST,major adverse cardiovascular events,or cerebrovascular events during follow-up.The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients,who were included to identify factors that predicted EST and to develop a prediction scoring system.The other 171 patients without integrated 1:2 pair were used for external validation.RESULTS:EST was independently associated with a low hemoglobin concentration(adjusted odds ratio[OR]0.946,95%confi dence interval[95%CI]0.901-0.993,P=0.026),a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score(OR 1.166,95%CI 1.049-1.297,P=0.004),and a DAPT(DAPT)duration of<30 days(OR 28.033,95%CI 5.302-272.834,P<0.001).The simple EST prediction score provided an area under the curve(AUC)of 0.854(95%CI 0.777-0.932,P<0.001)with 70.0%sensitivity and 90.0%specifi city,and 0.742(95%CI 0.649-0.835,P<0.001)with 54.5%sensitivity and 81.0%specifi city for external validation dataset.CONCLUSIONS:EST may be independently associated with DAPT discontinuation within 30 days,a low hemoglobin concentration,and a high SYNTAX score.The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.
基金Supported by National Natural Science Foundation of China,No.81670514 and No.81702337Scientific Research Project of Shanghai Municipal Health Commission,No.202040065Natural Science Foundation of Shanghai Scientific and Technological Project of Innovative Action,No.20ZR1411900.
文摘BACKGROUND The lack of effective pharmacotherapies for nonalcoholic fatty liver disease(NAFLD)is mainly attributed to insufficient research on its pathogenesis.The pathogenesis of TM6SF2-efficient NAFLD remains unclear,resulting in a lack of therapeutic strategies for TM6SF2-deficient patients.AIM To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency.METHODS Liver samples collected from both NAFLD mouse models and human participants(80 cases)were used to evaluate the expression of TM6SF2 by using western blotting,immunohistochemistry,and quantitative polymerase chain reaction.RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2.Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD.MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency.RESULTS Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models.TM6SF2 overexpression can reduce hepatic lipid accumulation,suggesting a protective role for TM6SF2 in a high-fat diet(HFD).Downregulation of TM6SF2,simulating the TM6SF2 E167K mutation condition,increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis,accompanied by impaired fatty acid oxidation.Owing to the potential effect of TM6SF2 deficiency on lipid metabolism,the application of an acetyl-CoA carboxylase inhibitor(MK-4074)could reverse the NAFLD phenotypes caused by TM6SF2 deficiency.CONCLUSION TM6SF2 plays a protective role in the HFD condition;its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism,and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.
基金supported by the National Natural Science Foundation of China(No.52001262)the Natural Science Foundation of Zhejiang Province,China(No.LZY22E010001)the Natural Science Foundation of Shaanxi Province,China(No.2020JC-50)。
文摘The in-situ micro-nano Ti_(2)AlC particles reinforced TiAl(Ti_(2)AlC/TiAl)composite was fabricated using spark plasma sintering.The hot workability of Ti_(2)AlC/TiAl composite was studied,and the effect of micro-nano particles on flow stress and dynamic recrystallization of composite was discussed.The results showed that the micro-nano Ti_(2)AlC particles included strengthening and softening effects during hot deformation,resulting in the fact that the Ti_(2)AlC/TiAl composite exhibited a higher flow stress and more sufficient dynamic recrystallization.The strengthening effect was mainly attributed to the Ti_(2)AlC particles induced refinement strengthening and hindered dislocation motion at the initial stage.Moreover,the precipitation of nano-TiCr2 particles induced by stress concentration during hot deformation also contributed to higher flow stress via impeding dislocation motion.Meanwhile,the refined microstructure and dislocation pile-up caused by micro-nano particles during deformation provided more nucleation sites for dynamic recrystallization,which significantly promoted the dynamic recrystallization of the second stage.The present results reveal that the Ti_(2)AlC/TiAl composite exhibited excellent hot workability,which is important to promote the application of TiAl alloys.
文摘F-652 is a recombinant fusion protein consisting of two human interleukin-22(IL-22)molecules linked to an immunoglobulin constant region(IgG 2-Fc).IL-22 plays critical roles in promoting tissue repair and suppressing bacterial infection.The safety,pharmacokinetics(PK),tolerability,and biomarkers of F-652 were evaluated following a single dose in healthy male volunteers in a randomized,double-blind,placebo-controlled study.Following single-dose subcutaneous(SC)injection of F-652 at 2.0µg/kg into healthy subjects,six out of six subjects experienced delayed injection site reactions,which presented as erythematous and/or discoid eczematous lesions 10 to 17 days post-dosing.F-652 was then administered to the healthy subjects via an intravenous(IV)infusion at 2.0,10,30,and 45µg/kg.No severe adverse event(SAE)was observed during the study.Among the IV-dosed cohorts,eye and skin treatment emergent adverse events(TEAEs)were observed in the 30 and 45µg/kg cohorts.F-652 IV dosing resulted in linear increases in C max and AUC(0–t),and the T 1/2 ranged from 39.4 to 206h in the cohorts.An IV injection of F-652 induced dose-dependent increases in serum marker serum amyloid A,C-reactive protein,and FIB,and decreased serum triglycerides.The serum levels of 36 common pro-inflammatory cytokines/chemokines were not altered by the treatment of F-652 at 45μg/kg.In conclusion,IV administration of F-652 to healthy male volunteers is safe and well-tolerated and demonstrates favorable PK and pharmacodynamic properties.These results warrant further clinical development of F-652 to treat inflammatory diseases.
基金the National Key R&D Pro-gram of China(Nos.2019YFC1315800,2019YFC1315802)National Natural Science Foundation of China(Nos.81830102,81772578,81802991),STCSM(No.18YF1403600)Shanghai Municipal Key Clinical Specialty.
文摘Background and Aims:The overall survival(OS)of hepatocellular carcinoma(HCC)remains dismal.Bioinformatic analysis of transcriptome data could identify patients with poor OS and may facilitate clinical decision.This study aimed to develop a prognostic gene model for HCC.Methods:GSE14520 was retrieved as a training set to identify differential expressed genes(DEGs)between tumor and adjacent liver tissues in HCC patients with different OS.A DEG-based prognostic model was then constructed and the TCGA-LIHC and ICGC-LIRI datasets were used to validate the model.The area under the receiver operating characteristic curve(AUC)and hazard ratio(HR)of the model for OS were calculated.A model-based nomogram was estab-lished and verified.Results:In the training set,differential expression analysis identified 80 genes dysregulated in oxidation-reduction and metabolism regulation.After univariate Cox and LASSO regression,eight genes(LPCAT1,DHRS1,SORBS2,ALDH5A1,SULT1C2,SPP1,HEY1 and GOLM1)were selected to build the prognostic model.The AUC for 1-,3-and 5-year OS were 0.779,0.736,0.754 in training set and 0.693,0.689,0.693 in the TCGA-LIHC validation set,respectively.The AUC for 1-and 3-year OS were 0.767 and 0.705 in the ICGC-LIRI validation set.Multivariate analysis confirmed the model was an independent prognostic factor(training set:HR=4.422,p<0.001;TCGA-LIHC validation set:HR=2.561,p<0.001;ICGC-LIRI validation set:HR=3.931,p<0.001).Furthermore,a nomogram combining the model and AJCC stage was established and validated,showing increased OS predictive efficacy compared with the prognostic model(p=0.035)or AJCC stage(p<0.001).Conclusions:Our eight-gene prognostic model and the related nomogram represent as reliable prognostic tools for OS prediction in HCC patients.
