Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the m...Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.展开更多
Objective To construct and verificate an RNA-binding protein(RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis.Methods RNA-sequencing and clinic pathological data of glioma patients...Objective To construct and verificate an RNA-binding protein(RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis.Methods RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas(TCGA)database and the Chinese Glioma Genome Atlas database(CGGA)were downloaded.The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database.We then identified prognosis related hub genes and constructed a prognostic model.This model was further validated in the CGGA-693 and CGGA-325 cohorts.Results Totally 174 differently expressed genes-encoded RBPs were identified,containing 85 down-regulated and 89 up-regulated genes.We identified five genes-encoded RBPs(ERI1,RPS2,BRCA1,NXT1,and TRIM21)as prognosis related key genes and constructed a prognostic model.Overall survival(OS)analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup.The area under the receiver operator characteristic curve(AUC)of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset,demonstrating a favorable prognostic model.Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings.A nomogram was constructed based on the five genes and validated in the TCGA cohort,confirming a promising discriminating ability for gliomas.Conclusion The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.展开更多
Objective:To comparatively investigate the ameliorative effect of Phellinus igniarius(P.igniarius)on renal aging in a rat model of focal and segmental glomerulosclerosis(FSGS).Methods:The FSGS model was established in...Objective:To comparatively investigate the ameliorative effect of Phellinus igniarius(P.igniarius)on renal aging in a rat model of focal and segmental glomerulosclerosis(FSGS).Methods:The FSGS model was established in rats by uninephrectomy combined with tail vein injection of doxorubicin.The FSGS rats were randomly divided into the model group,the P.igniarius decoction group,the P.igniarius polysaccharides group,and the P.igniarius polyphenols group.Molecular indicators of cell senescence,renal function indexes,and podocyte injury markers were tested after ten weeks of intragastric administration.Besides,the pathological renal lesions and the ultrastructural changes were observed.Results:FSGS developed in the model group within ten weeks and showed segmental glomerular scarring and renal aging.Following the 10-week intervention,24 h proteinuria,serum creatinine,blood urea nitrogen,P16^(INK4α),thrombospondin-1,and transforming growth factor-β1 were decreased in each treatment group,whereas albumin,erythropoietin,nephrin,and podocin were increased;the pathological renal injury was alleviated,and the number of senescent cells was reduced,especially in rats treated with P.igniarius decoction.Conclusions:P.igniarius ameliorates renal aging and renal injury in the FSGS rat model.Compared with the effective constituents(polysaccharides and polyphenols),P.igniarius decoction has a better curative effect,which is expected to provide a new therapeutic idea for FSGS.展开更多
Strong-field quantum electrodynamics(SF-QED)plays a crucial role in ultraintense laser-matter interactions and demands sophisticated techniques to understand the related physics with new degrees of freedom,including s...Strong-field quantum electrodynamics(SF-QED)plays a crucial role in ultraintense laser-matter interactions and demands sophisticated techniques to understand the related physics with new degrees of freedom,including spin angular momentum.To investigate the impact of SF-QED processes,we have introduced spin/polarization-resolved nonlinear Compton scattering,nonlinear Breit-Wheeler,and vacuum birefringence processes into our particle-in-cell(PIC)code.In this article,we provide details of the implementation of these SF-QED modules and share known results that demonstrate exact agreement with existing single-particle codes.By coupling normal PIC simulations with spin/polarization-resolved SF-QED processes,we create a new theoretical platform to study strong-field physics in currently running or planned petawatt or multi-petawatt laser facilities.展开更多
The rapid development of ultrafast ultraintense laser technology continues to create opportunities for studying strong-field physics under extreme conditions.However,accurate determination of the spatial and temporal ...The rapid development of ultrafast ultraintense laser technology continues to create opportunities for studying strong-field physics under extreme conditions.However,accurate determination of the spatial and temporal characteristics of a laser pulse is still a great challenge,especially when laser powers higher than hundreds of terawatts are involved.In this paper,by utilizing the radiative spin-flip effect,we find that the spin depolarization of an electron beam can be employed to diagnose characteristics of ultrafast ultraintense lasers with peak intensities around 10^(20)–10^(22) W/cm^(2).With three shots,our machine-learning-assisted model can predict,simultaneously,the pulse duration,peak intensity,and focal radius of a focused Gaussian ultrafast ultraintense laser(in principle,the profile can be arbitrary)with relative errors of 0.1%–10%.The underlying physics and an alternative diagnosis method(without the assistance of machine learning)are revealed by the asymptotic approximation of the final spin degree of polarization.Our proposed scheme exhibits robustness and detection accuracy with respect to fluctuations in the electron beam parameters.Accurate measurements of ultrafast ultraintense laser parameters will lead to much higher precision in,for example,laser nuclear physics investigations and laboratory astrophysics studies.Robust machine learning techniques may also find applications in more general strong-field physics scenarios.展开更多
Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuropr...Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937).展开更多
Objective To analyze the short-term outcomes of redo coronary artery bypass grafting(CABG) using on-pump and off-pump CABG techniques. Methods From January 2003 to August 2013, non-randomized 80 patients were treated ...Objective To analyze the short-term outcomes of redo coronary artery bypass grafting(CABG) using on-pump and off-pump CABG techniques. Methods From January 2003 to August 2013, non-randomized 80 patients were treated with redo CABG in the Department of Cardiac Surgery, Peking University Third Hospital. Among these patients, 40 underwent on-pump CABG technique(redo-ONCAB group) and 40 underwent off-pump CABG technique(redo-OPCAB group). Furthermore, transmyocardial laser revascularization was performed in high-risk patients who were not suitable to conventional grafting. Clinical data of the two groups were recorded and analyzed including operation time, coronary grafts, incomplete revascularization, postoperative ventilation, perioperative stroke, and low output syndrome, etc. Results There were no significantly differences in age, gender distribution, incidences of hypertension, stroke, and other clinical characteristics between redo-OPCAB group and redo-ONCAB group(all P>0.05), except for incidences of renal dysfunction and pulmonary disease(all P<0.05). The number of grafting vessels in the redo-ONCAB and redo-OPCAB groups was 2.1 ± 0.74 and 1.4 ±0.52 respectively. There was significant difference between the two groups(P=0.0243). Compared with the redo-ONCAB group, there was shorter operation time(P=0.0045), postoperative ventilation(P=0.0211) and intensive care unit stay(P=0.0400), as well as fewer use of platelet(P=0.0338) and blood transfusion(P=0.0034) in the redo-OPCAB group. The incidence of incomplete revascularization(P=0.0253) and the use of transmyocardial laser revascularization(P=0.0052) were higher in the redo-OPCAB group than those in the redo-ONCAB group(all P<0.05). However, no significant differences were showed for the incidence of the use of intra aortic balloon pump and continuous renal replacement therapy, perioperative stroke, low output syndrome, and in-hospital mortality between the two groups(all P>0.05). Conclusion Redo CABG is the safety and efficacy surgical procedure, and redo-OPCAB technique with better outcomes is commended especially in high-risk patients.展开更多
基金funded by the National Natural Science Foundation of China(82003879)Project of Science and Technology Department of Sichuan Province(2023NSFSC1928,2023NSFSC1992)+3 种基金Young Elite Scientists Sponsorship Program China Association for Science and Technology(CACM-2020-QNRC1-01)Project of State Administration of Traditional Chinese Medicine of China(ZYYCXTD-D-202209)Project of Undergraduate Training Programs for Innovation and Entrepreneurship(S202310610637)the Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources(SKLTCM202205).
文摘Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.
基金supported by the National Natural Science Foundation of China(No.82072795).
文摘Objective To construct and verificate an RNA-binding protein(RBP)-associated prognostic model for gliomas using integrated bioinformatics analysis.Methods RNA-sequencing and clinic pathological data of glioma patients from The Cancer Genome Atlas(TCGA)database and the Chinese Glioma Genome Atlas database(CGGA)were downloaded.The aberrantly expressed RBPs were investigated between gliomas and normal samples in TCGA database.We then identified prognosis related hub genes and constructed a prognostic model.This model was further validated in the CGGA-693 and CGGA-325 cohorts.Results Totally 174 differently expressed genes-encoded RBPs were identified,containing 85 down-regulated and 89 up-regulated genes.We identified five genes-encoded RBPs(ERI1,RPS2,BRCA1,NXT1,and TRIM21)as prognosis related key genes and constructed a prognostic model.Overall survival(OS)analysis revealed that the patients in the high-risk subgroup based on the model were worse than those in the low-risk subgroup.The area under the receiver operator characteristic curve(AUC)of the prognostic model was 0.836 in the TCGA dataset and 0.708 in the CGGA-693 dataset,demonstrating a favorable prognostic model.Survival analyses of the five RBPs in the CGGA-325 cohort validated the findings.A nomogram was constructed based on the five genes and validated in the TCGA cohort,confirming a promising discriminating ability for gliomas.Conclusion The prognostic model of the five RBPs might serve as an independent prognostic algorithm for gliomas.
基金supported by the Public Welfare Technology Application Research Program of Zhejiang Province (LGC21H290002)Key Projects of Zhejiang Administration of Traditional Chinese Medicine (2020ZZ016).
文摘Objective:To comparatively investigate the ameliorative effect of Phellinus igniarius(P.igniarius)on renal aging in a rat model of focal and segmental glomerulosclerosis(FSGS).Methods:The FSGS model was established in rats by uninephrectomy combined with tail vein injection of doxorubicin.The FSGS rats were randomly divided into the model group,the P.igniarius decoction group,the P.igniarius polysaccharides group,and the P.igniarius polyphenols group.Molecular indicators of cell senescence,renal function indexes,and podocyte injury markers were tested after ten weeks of intragastric administration.Besides,the pathological renal lesions and the ultrastructural changes were observed.Results:FSGS developed in the model group within ten weeks and showed segmental glomerular scarring and renal aging.Following the 10-week intervention,24 h proteinuria,serum creatinine,blood urea nitrogen,P16^(INK4α),thrombospondin-1,and transforming growth factor-β1 were decreased in each treatment group,whereas albumin,erythropoietin,nephrin,and podocin were increased;the pathological renal injury was alleviated,and the number of senescent cells was reduced,especially in rats treated with P.igniarius decoction.Conclusions:P.igniarius ameliorates renal aging and renal injury in the FSGS rat model.Compared with the effective constituents(polysaccharides and polyphenols),P.igniarius decoction has a better curative effect,which is expected to provide a new therapeutic idea for FSGS.
基金The work is supported by the National Natural Science Foundation of China(Grant Nos.12275209,12022506,and U2267204)the Open Foundation of the Key Laboratory of High Power Laser and Physics,Chinese Academy of Sciences(Grant No.SGKF202101)+1 种基金the Foundation of Science and Technology on Plasma Physics Laboratory(Grant No.JCKYS2021212008)the Shaanxi Fundamental Science Research Project for Mathematics and Physics(Grant No.22JSY014).
文摘Strong-field quantum electrodynamics(SF-QED)plays a crucial role in ultraintense laser-matter interactions and demands sophisticated techniques to understand the related physics with new degrees of freedom,including spin angular momentum.To investigate the impact of SF-QED processes,we have introduced spin/polarization-resolved nonlinear Compton scattering,nonlinear Breit-Wheeler,and vacuum birefringence processes into our particle-in-cell(PIC)code.In this article,we provide details of the implementation of these SF-QED modules and share known results that demonstrate exact agreement with existing single-particle codes.By coupling normal PIC simulations with spin/polarization-resolved SF-QED processes,we create a new theoretical platform to study strong-field physics in currently running or planned petawatt or multi-petawatt laser facilities.
基金This work is supported by the National Natural Science Foundation of China(Grant Nos.11874295,12022506,U2267204,11905169,12275209,11875219,and 12171383)the Open Fund of the State Key Laboratory of High Field Laser Physics(Shanghai Institute of Optics and Fine Mechanics)+1 种基金the Foundation of Science and Technology on Plasma Physics Laboratory(Grant No.JCKYS2021212008)The work of Y.I.S.is supported by an American University of Sharjah Faculty Research(Grant No.FRG21).
文摘The rapid development of ultrafast ultraintense laser technology continues to create opportunities for studying strong-field physics under extreme conditions.However,accurate determination of the spatial and temporal characteristics of a laser pulse is still a great challenge,especially when laser powers higher than hundreds of terawatts are involved.In this paper,by utilizing the radiative spin-flip effect,we find that the spin depolarization of an electron beam can be employed to diagnose characteristics of ultrafast ultraintense lasers with peak intensities around 10^(20)–10^(22) W/cm^(2).With three shots,our machine-learning-assisted model can predict,simultaneously,the pulse duration,peak intensity,and focal radius of a focused Gaussian ultrafast ultraintense laser(in principle,the profile can be arbitrary)with relative errors of 0.1%–10%.The underlying physics and an alternative diagnosis method(without the assistance of machine learning)are revealed by the asymptotic approximation of the final spin degree of polarization.Our proposed scheme exhibits robustness and detection accuracy with respect to fluctuations in the electron beam parameters.Accurate measurements of ultrafast ultraintense laser parameters will lead to much higher precision in,for example,laser nuclear physics investigations and laboratory astrophysics studies.Robust machine learning techniques may also find applications in more general strong-field physics scenarios.
文摘Cattle encephalon glycoside and ignotin(CEGI)injection is a compound preparation formed by a combination of muscle extract from hea lthy rabbits and brain gangliosides from cattle,and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries.However,there is still a need for high-level clinical evidence from large samples to support the use of CEGI.We therefore carried out a prospective,multicenter,randomized,double-blind,parallel-group,placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016.The patients were randomized at a 3:1 ratio into CEGI(n=239;155 male,84 female;61.2±9.2 years old)and placebo(n=80;46 male,34 female;63.2±8.28 years old)groups.All patients were given standard care once daily for 14 days,including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium,both taken orally,and intravenous infusion of 250–500 mL 0.9%sodium chloride containing 40 mg sodium tanshinone IIA sulfonate.Based on conventional treatment,patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water,respectively,in an intravenous drip of 250 mL 0.9%sodium chloride(2 mL/min)once daily for 14 days.According to baseline National Institutes of Health Stroke Scale scores,patients in the two groups were divided into mild and moderate subgroups.Based on the modified Rankin Scale results,the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group,and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment.In the CEGI group,neurological deficits were decreased on days 14 and 90 after treatment,as measured by the National Institutes of Health Stroke Scale and the Barthel Index.Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients.No drug-related adverse events occurred in the CEGI or placebo groups.In conclusion,CEGI may be a safe and effective treatment for acute cerebral infarction patients,especially for moderate stroke patients.This study was approved by the Ethical Committee of Peking University Third Hospital,China(approval No.2013-068-2)on May 20,2013,and registered in the Chinese Clinical Trial Registry(registration No.ChiCTR1800017937).
文摘Objective To analyze the short-term outcomes of redo coronary artery bypass grafting(CABG) using on-pump and off-pump CABG techniques. Methods From January 2003 to August 2013, non-randomized 80 patients were treated with redo CABG in the Department of Cardiac Surgery, Peking University Third Hospital. Among these patients, 40 underwent on-pump CABG technique(redo-ONCAB group) and 40 underwent off-pump CABG technique(redo-OPCAB group). Furthermore, transmyocardial laser revascularization was performed in high-risk patients who were not suitable to conventional grafting. Clinical data of the two groups were recorded and analyzed including operation time, coronary grafts, incomplete revascularization, postoperative ventilation, perioperative stroke, and low output syndrome, etc. Results There were no significantly differences in age, gender distribution, incidences of hypertension, stroke, and other clinical characteristics between redo-OPCAB group and redo-ONCAB group(all P>0.05), except for incidences of renal dysfunction and pulmonary disease(all P<0.05). The number of grafting vessels in the redo-ONCAB and redo-OPCAB groups was 2.1 ± 0.74 and 1.4 ±0.52 respectively. There was significant difference between the two groups(P=0.0243). Compared with the redo-ONCAB group, there was shorter operation time(P=0.0045), postoperative ventilation(P=0.0211) and intensive care unit stay(P=0.0400), as well as fewer use of platelet(P=0.0338) and blood transfusion(P=0.0034) in the redo-OPCAB group. The incidence of incomplete revascularization(P=0.0253) and the use of transmyocardial laser revascularization(P=0.0052) were higher in the redo-OPCAB group than those in the redo-ONCAB group(all P<0.05). However, no significant differences were showed for the incidence of the use of intra aortic balloon pump and continuous renal replacement therapy, perioperative stroke, low output syndrome, and in-hospital mortality between the two groups(all P>0.05). Conclusion Redo CABG is the safety and efficacy surgical procedure, and redo-OPCAB technique with better outcomes is commended especially in high-risk patients.