Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and...Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.展开更多
【目的】研究一次性施肥技术对黄淮海夏玉米产量、肥料利用效率和经济效益的影响,为黄淮海夏玉米区实现减肥增效、节本增收及轻简化生产技术的筛选提供理论依据。【方法】2015年和2016年在河北、河南、山东三省选择8个试验地点进行控释...【目的】研究一次性施肥技术对黄淮海夏玉米产量、肥料利用效率和经济效益的影响,为黄淮海夏玉米区实现减肥增效、节本增收及轻简化生产技术的筛选提供理论依据。【方法】2015年和2016年在河北、河南、山东三省选择8个试验地点进行控释氮肥随夏玉米播种一次性施用大田试验。与普通氮肥分次施用(习惯施肥(FP)和优化施肥(OPT))对比,通过设置控释氮肥等量投入(CRFA)、减量20%控释氮肥投入(CRFA80%N、CRFB80%N和CRFC80%N),研究一次性施肥技术对黄淮海夏玉米经济效益的影响,并验证一次性施肥技术的减量施氮可行性。【结果】(1)与农民习惯施肥(FP)相比,一次性施肥处理对黄淮海区夏玉米株高、穗部性状和两年的平均产量均无显著影响,氮肥农学效率和表观利用率虽有所提高,但未达显著性差异;但一次性减氮施肥处理较FP处理,氮肥偏生产力显著提高了33.85%以上(P<0.05)。此外,CRFA、CRFA80%N、CRFB80%N和CRFC80%N处理相比农民习惯施肥(FP),每季平均节氮量分别为8.15、50.65、50.65、50.65 kg N·hm^(-2),增加纯收入927.40元/hm^2以上。(2)除CRFA处理外,其余一次性施肥处理的硝态氮量均显著低于习惯施肥处理(FP);一次性减氮施肥处理(CRFA80%N、CRFB80%N、CRFC80%N)0—90 cm土层NO_3^--N含量显著低于优化施肥处理(OPT)(P<0.05)。【结论】一次性施肥技术实现了黄淮海夏玉米的轻简化施肥,提高了氮肥的利用效率,能够在保证稳产增产的前提下,实现氮肥的减量施用;推荐减少20%氮用量的CRFA施肥模式在黄淮海夏玉米生产上一次性施用。展开更多
Donor shortages for organ transplantations are a major clinical challenge worldwide. Potential risks that are inevitably encountered with traditional methods include complications, secondary injuries, and limited sour...Donor shortages for organ transplantations are a major clinical challenge worldwide. Potential risks that are inevitably encountered with traditional methods include complications, secondary injuries, and limited source donors. Three-dimensional （3D） printing technology holds the potential to solve these limitations; it can he used to rapidly manufacture personalized tissue engineering scaffolds, repair tissue defects in situ with cells, and even directly print tissue and organs. Such printed implants and organs not only perfectly match the patient＇s damaged tissue, hut can also have engineered material microstructures and cell arrangements to promote cell growth and differentiation. Thus, such implants allow the desired tissue repair to he achieved, and could eventually solve the donor-shortage problem. This review summarizes relevant studies and recent progress on four levels, introduces different types of biomedical materials, and discusses existing problems and development issues with 3D printing that are related to materials and to the construction of extracellular matrix in vitro for medical applications.展开更多
Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to ...Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintili展开更多
Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this rand...Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this randomized phase 3 trial,we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen.Eligible patients were randomized(1:1:1)to receive chiglitazar 32 mg(n=245),chiglitazar 48 mg(n=246),or sitagliptin 100 mg(n=248)once daily for 24 weeks.The primary endpoint was the change in glycosylated hemoglobin A_(1C)(HbA_(1c))from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin.Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of-1.40%,-1.47%,and-1.39%for chiglitazar 32 mg,chiglitazar 48 mg,and sitagliptin 100 mg,respectively.Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg,with mean differences of-0.04%(95%confidential interval(Cl)-0.22 to 0.15)and-0.08%(95%Cl-0.27 to 0.10),respectively.Compared with sitagliptin,greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar.Overall adverse event rates were similar between the groups.A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported.The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.展开更多
Objective： To evaluate the feasibility and safety of total mesopancreas excision （TMpE） in the treatment of pancreatic head cancer. Methods： The clinical and pathological data of 120 patients with pancreatic head ...Objective： To evaluate the feasibility and safety of total mesopancreas excision （TMpE） in the treatment of pancreatic head cancer. Methods： The clinical and pathological data of 120 patients with pancreatic head cancer who had undergone TMpE in our center from May 2010 to January 2014 were retrospectively analyzed. Results： The mean operative time was （275.0±50.2） min and the average intra-operative blood loss was （390.0±160.5） mL. Post-operative complications were reported in 45 patients, while no peri-operative death was noted. The specimen margins were measured in three dimensions, and 86 patients （71.6%） achieved R0 resection. Conclusions： TMpE is safe and feasible for pancreatic head cancer and is particularly helpful to increase the R0 resection rate.展开更多
文摘Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.
文摘【目的】研究一次性施肥技术对黄淮海夏玉米产量、肥料利用效率和经济效益的影响,为黄淮海夏玉米区实现减肥增效、节本增收及轻简化生产技术的筛选提供理论依据。【方法】2015年和2016年在河北、河南、山东三省选择8个试验地点进行控释氮肥随夏玉米播种一次性施用大田试验。与普通氮肥分次施用(习惯施肥(FP)和优化施肥(OPT))对比,通过设置控释氮肥等量投入(CRFA)、减量20%控释氮肥投入(CRFA80%N、CRFB80%N和CRFC80%N),研究一次性施肥技术对黄淮海夏玉米经济效益的影响,并验证一次性施肥技术的减量施氮可行性。【结果】(1)与农民习惯施肥(FP)相比,一次性施肥处理对黄淮海区夏玉米株高、穗部性状和两年的平均产量均无显著影响,氮肥农学效率和表观利用率虽有所提高,但未达显著性差异;但一次性减氮施肥处理较FP处理,氮肥偏生产力显著提高了33.85%以上(P<0.05)。此外,CRFA、CRFA80%N、CRFB80%N和CRFC80%N处理相比农民习惯施肥(FP),每季平均节氮量分别为8.15、50.65、50.65、50.65 kg N·hm^(-2),增加纯收入927.40元/hm^2以上。(2)除CRFA处理外,其余一次性施肥处理的硝态氮量均显著低于习惯施肥处理(FP);一次性减氮施肥处理(CRFA80%N、CRFB80%N、CRFC80%N)0—90 cm土层NO_3^--N含量显著低于优化施肥处理(OPT)(P<0.05)。【结论】一次性施肥技术实现了黄淮海夏玉米的轻简化施肥,提高了氮肥的利用效率,能够在保证稳产增产的前提下,实现氮肥的减量施用;推荐减少20%氮用量的CRFA施肥模式在黄淮海夏玉米生产上一次性施用。
文摘Donor shortages for organ transplantations are a major clinical challenge worldwide. Potential risks that are inevitably encountered with traditional methods include complications, secondary injuries, and limited source donors. Three-dimensional （3D） printing technology holds the potential to solve these limitations; it can he used to rapidly manufacture personalized tissue engineering scaffolds, repair tissue defects in situ with cells, and even directly print tissue and organs. Such printed implants and organs not only perfectly match the patient＇s damaged tissue, hut can also have engineered material microstructures and cell arrangements to promote cell growth and differentiation. Thus, such implants allow the desired tissue repair to he achieved, and could eventually solve the donor-shortage problem. This review summarizes relevant studies and recent progress on four levels, introduces different types of biomedical materials, and discusses existing problems and development issues with 3D printing that are related to materials and to the construction of extracellular matrix in vitro for medical applications.
基金funded by Innovent biologics,Inc.Eli Lilly and Companypartly supported by China National Major Project for New Drug Innovation(2017ZX09304015).
文摘Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintili
基金the Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002,2013ZX09401301Provincial:2011A080501010)Shenzhen Municipal Major Project(2010-1746)。
文摘Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this randomized phase 3 trial,we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen.Eligible patients were randomized(1:1:1)to receive chiglitazar 32 mg(n=245),chiglitazar 48 mg(n=246),or sitagliptin 100 mg(n=248)once daily for 24 weeks.The primary endpoint was the change in glycosylated hemoglobin A_(1C)(HbA_(1c))from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin.Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of-1.40%,-1.47%,and-1.39%for chiglitazar 32 mg,chiglitazar 48 mg,and sitagliptin 100 mg,respectively.Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg,with mean differences of-0.04%(95%confidential interval(Cl)-0.22 to 0.15)and-0.08%(95%Cl-0.27 to 0.10),respectively.Compared with sitagliptin,greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar.Overall adverse event rates were similar between the groups.A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported.The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.
基金Supported by Shanghai municipal hospital burgeoning and leading edge technology projects No.SHDC12014109
文摘Objective： To evaluate the feasibility and safety of total mesopancreas excision （TMpE） in the treatment of pancreatic head cancer. Methods： The clinical and pathological data of 120 patients with pancreatic head cancer who had undergone TMpE in our center from May 2010 to January 2014 were retrospectively analyzed. Results： The mean operative time was （275.0±50.2） min and the average intra-operative blood loss was （390.0±160.5） mL. Post-operative complications were reported in 45 patients, while no peri-operative death was noted. The specimen margins were measured in three dimensions, and 86 patients （71.6%） achieved R0 resection. Conclusions： TMpE is safe and feasible for pancreatic head cancer and is particularly helpful to increase the R0 resection rate.
