Background:The associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for hepatocellular carcinoma(HCC)with fibrosis/cirrhosis is often associated with limited growth of future liver remnant...Background:The associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for hepatocellular carcinoma(HCC)with fibrosis/cirrhosis is often associated with limited growth of future liver remnant(FLR).We introduced a new procedure named transcatheter arterial embolization-salvaged ALPPS(TAE-salvaged ALPPS)which was shown to be especially suitable for HCC patients with cirrhosis or fibrosis who failed adequately to respond to conventional ALPPS.The short-term efficacy and safety for the TAE-salvaged ALPPS on patients with HCC and fibrosis/cirrhosis were studied.Methods:Consecutive HCC patients who underwent TAE-salvaged ALPPS in our hospital between November 2016 and June 2020 were retrospectively studied.The new ALPPS procedure included conventional ALPPS stage-1 using associating liver partition and portal vein ligation.When FLR failed to reach sufficient hypertrophy,TAE was carried out 2 weeks later followed by liver resection 3 weeks after ALPPS stage-1.Results:Nine of 10 patients had a single tumor(median diameter 14.0 cm,range,5.2-17 cm).The remaining patient had multiple tumors(diameter of one tumor 14.0 cm,and two satellite foci 2.0 and 3.0 cm).R0 resection was achieved in all patients(100%)after a median of 21 days.Six patients had cirrhosis,1 had METAVIR grade-3 fibrosis,and 3 had METAVIR grade-2 fibrosis.The median increase in FLR volume after TAE-salvaged ALPPS was 69.7%(34.4-143.9%).The absolute and relative kinetic growth rates(KGRs)were 9.9(7.1-17.3)mL/day and 3.4%(1.9-7.2%)/day,respectively.The median absolute KGRs were 15.7,2.6,and 19.5 mL/day in the first,second,and third postoperative weeks after ALPPS stage-1,respectively.The rapid increase in KGR on the third week was induced by TAE.The overall postoperative morbidity rates were 50,0%(5/10),20.0%(2/10)and 70.0%(7/10)after ALPPS stage-1,TAE and ALPPS stage-2,respectively.The 90-day mortality rate was 10.0%(1/10).The median overall survival was 40 months.Conclusions:The new TAE-salvaged ALPPS induced significant increases i展开更多
TRIZ含义即发明问题解决理论,其英文缩写为TIPS(theory of inventive problem solving)。文章首先介绍了TRIZ的基本概念、诞生、发展、TRIZ的作用及现有的理论体系,然后进行了TRIZ理论在科研创新管理中的作用分析,同时用实例探讨了TRIZ...TRIZ含义即发明问题解决理论,其英文缩写为TIPS(theory of inventive problem solving)。文章首先介绍了TRIZ的基本概念、诞生、发展、TRIZ的作用及现有的理论体系,然后进行了TRIZ理论在科研创新管理中的作用分析,同时用实例探讨了TRIZ在管理产品创新或者解决技术难题中的应用,论文在最后总结了国内一些研究所、企业进行TRIZ管理实践的经验,同时也给出了运用TRIZ对科研进行管理的一些思考建议。展开更多
Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and sa...Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.展开更多
为实现鸭星状病毒1型(Duck astrovirus type 1,DAstV-1)的快速检测,本试验针对DAstV-1(WF1202株)保守区域设计特异性引物,建立了基于染料SYBR GreenⅠ的实时荧光定量PCR(qPCR)方法,利用所建方法对临床样本进行检测,并将其应用于阳性样...为实现鸭星状病毒1型(Duck astrovirus type 1,DAstV-1)的快速检测,本试验针对DAstV-1(WF1202株)保守区域设计特异性引物,建立了基于染料SYBR GreenⅠ的实时荧光定量PCR(qPCR)方法,利用所建方法对临床样本进行检测,并将其应用于阳性样本病毒的分离和鉴定。结果表明所建qPCR检测方法的检测下限为4.64×10^(3)拷贝/μL,高于普通RT-PCR方法10倍;对禽类其他常见病原均为阴性,特异性良好;批内、批间变异系数(Cv)分别为0.85%~2.85%和0.21%~2.94%,均低于3.00%,表明其重复性良好。利用该方法对2020-2022年间10省份不同鸭场的35份组织病料进行检测,阳性率为25.71%(9/35),与普通RT-PCR检测结果的符合率为94.29%。任取1份阳性病料接种健康鸭胚进行病毒的分离,收集尿囊液利用所建qPCR方法进行检测,确定为阳性后接种1日龄健康雏鸭进行动物回归试验,感染雏鸭呈现一过性发病但未出现死亡,qPCR检测DAstV-1均为阳性,剖检可见肝脏有轻微出血,病理组织学观察发现肝细胞空泡变性,说明所分离的DAstV-1毒株致病性较弱。综上,本试验成功建立了DAstV-1的荧光定量PCR检测方法,可为DAstV-1的临床诊断、分离鉴定及分子流行病学监测等提供技术支撑。展开更多
MicroRNAs(miRNAs)are aberrantly expressed in the pathophysiologic process of heart failure(HF).However,the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported,which might be co...MicroRNAs(miRNAs)are aberrantly expressed in the pathophysiologic process of heart failure(HF).However,the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported,which might be covered by the globe effects of it on the heart.In the current study,Langendorff system was applied to isolate card io myocytes(CMs)and cardiac fibroblasts(CFs)from transverse aortic constriction(TAC)-induced mice.Slight increase of miR-320 expression was observed in the whole heart tissue of TAC mice.Interestingly,miR-320 was significantly elevated in CMs but decreased in CFs from TAC mice at different time points.Then,recombinant adeno-associated virus 9 with cell-type-specific promoters were used to manipulate miR-320 expressions in vivo.Both in vitro and in vivo experiments showed the miR-320 overexpression in CMs exacerbated cardiac dysfunction,whereas overexpression of miR-320 in CFs alleviated cardiac fibrosis and hypertrophy.Mechanically,downstream signaling pathway analyses revealed that miR-320 might induce various effects via targeting PLEKHM3 and IFITM1 in CMs and CFs,respectively.Moreover,miR-320 mediated effects could be abolished by PLEKHM3 re-expression in CMs or IFITM1 re-expression in CFs.Interestingly,miR-320 treated CFs were able to indirectly affect CMs function,but not vice versa.Meanwhile,upstream signaling pathway analyses showed that miR-320 expression and decay rate were rigorously manipulated by Ago2,which was regulated by a cluster of cell-type-specific TFs distinctively expressed in CMs and CFs,respectively.Together,we demonstrated that miR-320 functioned differently in various cell types of the heart during the progression of HF.展开更多
Attaining a highly efficient and inexpensive electrocatalyst is significant for the hydrogen evolution reaction(HER)but still challenging nowadays.The transition-metal phosphides(TMPs)catalysts with platinum-like elec...Attaining a highly efficient and inexpensive electrocatalyst is significant for the hydrogen evolution reaction(HER)but still challenging nowadays.The transition-metal phosphides(TMPs)catalysts with platinum-like electronic structures are a potential candidate for the HER,but those are prone to be strongly bound with hydrogen intermediates(H∗),resulting in sluggish HER kinetics.Herein we report a unique hybrid structure of CoP anchored on graphene nanoscrolls@carbon nano tubes(CNTs)scaffold(Ni M@C-CoP)encapsulating various Ni M(M=Zn,Mo,Ni,Co)bimetal nanoalloy via chemical vapor deposi-tion(CVD)growth of CNT on graphene nanoscrolls followed by the impregnation of cobalt precursors and phosphorization for efficiently electrocatalytic hydrogen evolution.CoP nanoparticles mainly scattered at the tip of CNT branches which exhibited the analogical“Three-layer core-shell”structures.Experiments and density functional theory(DFT)calculations consistently disclose that the encapsulated various NiMs can offer different numbers of electrons to weaken the interactions of outmost CoP with H∗and push the downshift of the d-band center to different degrees as well as stabilize the outmost CoP nanopar-ticles to gain catalytic stability via the electron traversing effect.The electrocatalytic HER activity can be maximumly enhanced with low overpotentials of 78 mV(alkaline)and 89 mV(acidic)at a current density of 10 mA/cm^(2) and sustained at least 24 h especially for NiZn@C-CoP catalyst.This novel system is distinct from conventional three-layer heterostructure,providing a specially thought of d-band center control engineering strategy for the design of heterogeneous catalysts and expanding to other electrocat-alysts,energy storage,sensing,and other applications.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(No.82150004).
文摘Background:The associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for hepatocellular carcinoma(HCC)with fibrosis/cirrhosis is often associated with limited growth of future liver remnant(FLR).We introduced a new procedure named transcatheter arterial embolization-salvaged ALPPS(TAE-salvaged ALPPS)which was shown to be especially suitable for HCC patients with cirrhosis or fibrosis who failed adequately to respond to conventional ALPPS.The short-term efficacy and safety for the TAE-salvaged ALPPS on patients with HCC and fibrosis/cirrhosis were studied.Methods:Consecutive HCC patients who underwent TAE-salvaged ALPPS in our hospital between November 2016 and June 2020 were retrospectively studied.The new ALPPS procedure included conventional ALPPS stage-1 using associating liver partition and portal vein ligation.When FLR failed to reach sufficient hypertrophy,TAE was carried out 2 weeks later followed by liver resection 3 weeks after ALPPS stage-1.Results:Nine of 10 patients had a single tumor(median diameter 14.0 cm,range,5.2-17 cm).The remaining patient had multiple tumors(diameter of one tumor 14.0 cm,and two satellite foci 2.0 and 3.0 cm).R0 resection was achieved in all patients(100%)after a median of 21 days.Six patients had cirrhosis,1 had METAVIR grade-3 fibrosis,and 3 had METAVIR grade-2 fibrosis.The median increase in FLR volume after TAE-salvaged ALPPS was 69.7%(34.4-143.9%).The absolute and relative kinetic growth rates(KGRs)were 9.9(7.1-17.3)mL/day and 3.4%(1.9-7.2%)/day,respectively.The median absolute KGRs were 15.7,2.6,and 19.5 mL/day in the first,second,and third postoperative weeks after ALPPS stage-1,respectively.The rapid increase in KGR on the third week was induced by TAE.The overall postoperative morbidity rates were 50,0%(5/10),20.0%(2/10)and 70.0%(7/10)after ALPPS stage-1,TAE and ALPPS stage-2,respectively.The 90-day mortality rate was 10.0%(1/10).The median overall survival was 40 months.Conclusions:The new TAE-salvaged ALPPS induced significant increases i
文摘TRIZ含义即发明问题解决理论,其英文缩写为TIPS(theory of inventive problem solving)。文章首先介绍了TRIZ的基本概念、诞生、发展、TRIZ的作用及现有的理论体系,然后进行了TRIZ理论在科研创新管理中的作用分析,同时用实例探讨了TRIZ在管理产品创新或者解决技术难题中的应用,论文在最后总结了国内一些研究所、企业进行TRIZ管理实践的经验,同时也给出了运用TRIZ对科研进行管理的一些思考建议。
文摘Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.
文摘为实现鸭星状病毒1型(Duck astrovirus type 1,DAstV-1)的快速检测,本试验针对DAstV-1(WF1202株)保守区域设计特异性引物,建立了基于染料SYBR GreenⅠ的实时荧光定量PCR(qPCR)方法,利用所建方法对临床样本进行检测,并将其应用于阳性样本病毒的分离和鉴定。结果表明所建qPCR检测方法的检测下限为4.64×10^(3)拷贝/μL,高于普通RT-PCR方法10倍;对禽类其他常见病原均为阴性,特异性良好;批内、批间变异系数(Cv)分别为0.85%~2.85%和0.21%~2.94%,均低于3.00%,表明其重复性良好。利用该方法对2020-2022年间10省份不同鸭场的35份组织病料进行检测,阳性率为25.71%(9/35),与普通RT-PCR检测结果的符合率为94.29%。任取1份阳性病料接种健康鸭胚进行病毒的分离,收集尿囊液利用所建qPCR方法进行检测,确定为阳性后接种1日龄健康雏鸭进行动物回归试验,感染雏鸭呈现一过性发病但未出现死亡,qPCR检测DAstV-1均为阳性,剖检可见肝脏有轻微出血,病理组织学观察发现肝细胞空泡变性,说明所分离的DAstV-1毒株致病性较弱。综上,本试验成功建立了DAstV-1的荧光定量PCR检测方法,可为DAstV-1的临床诊断、分离鉴定及分子流行病学监测等提供技术支撑。
基金supported by grant from the National Natural Science Foundation of China(nos.81822002,31771264,31800973,and 81630010).
文摘MicroRNAs(miRNAs)are aberrantly expressed in the pathophysiologic process of heart failure(HF).However,the functions of a certain miRNA in different cardiac cell types during HF are scarcely reported,which might be covered by the globe effects of it on the heart.In the current study,Langendorff system was applied to isolate card io myocytes(CMs)and cardiac fibroblasts(CFs)from transverse aortic constriction(TAC)-induced mice.Slight increase of miR-320 expression was observed in the whole heart tissue of TAC mice.Interestingly,miR-320 was significantly elevated in CMs but decreased in CFs from TAC mice at different time points.Then,recombinant adeno-associated virus 9 with cell-type-specific promoters were used to manipulate miR-320 expressions in vivo.Both in vitro and in vivo experiments showed the miR-320 overexpression in CMs exacerbated cardiac dysfunction,whereas overexpression of miR-320 in CFs alleviated cardiac fibrosis and hypertrophy.Mechanically,downstream signaling pathway analyses revealed that miR-320 might induce various effects via targeting PLEKHM3 and IFITM1 in CMs and CFs,respectively.Moreover,miR-320 mediated effects could be abolished by PLEKHM3 re-expression in CMs or IFITM1 re-expression in CFs.Interestingly,miR-320 treated CFs were able to indirectly affect CMs function,but not vice versa.Meanwhile,upstream signaling pathway analyses showed that miR-320 expression and decay rate were rigorously manipulated by Ago2,which was regulated by a cluster of cell-type-specific TFs distinctively expressed in CMs and CFs,respectively.Together,we demonstrated that miR-320 functioned differently in various cell types of the heart during the progression of HF.
基金This work was supported by the Science and Technology Pro-gram of Shaanxi Province(No.2019GY-200).Shengwu Guo and Wei Wang contributed to the material TEM and SEM characterizations in this work.
文摘Attaining a highly efficient and inexpensive electrocatalyst is significant for the hydrogen evolution reaction(HER)but still challenging nowadays.The transition-metal phosphides(TMPs)catalysts with platinum-like electronic structures are a potential candidate for the HER,but those are prone to be strongly bound with hydrogen intermediates(H∗),resulting in sluggish HER kinetics.Herein we report a unique hybrid structure of CoP anchored on graphene nanoscrolls@carbon nano tubes(CNTs)scaffold(Ni M@C-CoP)encapsulating various Ni M(M=Zn,Mo,Ni,Co)bimetal nanoalloy via chemical vapor deposi-tion(CVD)growth of CNT on graphene nanoscrolls followed by the impregnation of cobalt precursors and phosphorization for efficiently electrocatalytic hydrogen evolution.CoP nanoparticles mainly scattered at the tip of CNT branches which exhibited the analogical“Three-layer core-shell”structures.Experiments and density functional theory(DFT)calculations consistently disclose that the encapsulated various NiMs can offer different numbers of electrons to weaken the interactions of outmost CoP with H∗and push the downshift of the d-band center to different degrees as well as stabilize the outmost CoP nanopar-ticles to gain catalytic stability via the electron traversing effect.The electrocatalytic HER activity can be maximumly enhanced with low overpotentials of 78 mV(alkaline)and 89 mV(acidic)at a current density of 10 mA/cm^(2) and sustained at least 24 h especially for NiZn@C-CoP catalyst.This novel system is distinct from conventional three-layer heterostructure,providing a specially thought of d-band center control engineering strategy for the design of heterogeneous catalysts and expanding to other electrocat-alysts,energy storage,sensing,and other applications.
