Synchronous reluctance motors(SynRM)are widely employed in industrial applications due to their high robustness,low cost,and absence of permanent magnets.In recent years,significant research efforts have focused on im...Synchronous reluctance motors(SynRM)are widely employed in industrial applications due to their high robustness,low cost,and absence of permanent magnets.In recent years,significant research efforts have focused on improving the controllability and efficiency of SynRM.Accurate rotor position information is essential for the controller to generate appropriate current and voltage references corresponding to the desired speed and load torque.Shaft-mounted position sensors are generally undesirable because of their high cost,sensitivity to harsh operating conditions,maintenance requirements,and reduced reliability in environments characterized by high vibration.Consequently,sensorless control techniques that estimate rotor position using measured stator currents and voltages have attracted increasing attention.However,magnetic saturation,parameter nonlinearities,and cross-coupling effects significantly degrade position estimation accuracy and may compromise the stability of sensorless SynRM drives.In this paper,a nonlinear SynRM model is developed using finite element analysis(FEA)to accurately capture magnetic saturation and cross-coupling effects,thereby providing a precise representation of the machine’s electromagnetic behavior under varying load and flux conditions.A series of magnetostatic FEA simulations is performed.To reduce computational complexity,only one motor pole is analyzed by applying anti-periodic boundary conditions along the domain sides and enforcing a zero magnetic vector potential on the external stator boundary.Nonlinear iron material properties are modeled using the appropriate B-H curve.The simulations are carried out by imposing d-and q-axis current components and computing the corresponding flux linkages and electromagnetic torque.Based on these results,both apparent and incremental inductances are extracted and incorporated into the control algorithm.An advanced fictitious flux linkage method combined with a phase-locked loop(PLL)is employed for accurate rotor position estimation.Simulation results confirm that the proposed sensorless control strategy ensures stable operation and high position estimation accuracy over the entire speed range.展开更多
Background： The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one...Background： The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one of the treatment options for gastric cancer patients after radical gastrectomy with D2 lymph node excision. Methods： We have commenced a randomized phase III trial in December 2016 to evaluate S-I plus oxaliplatin compared with S-1 alone in the adjuvant setting for locally advanced gastric cancer. A total of 564 patients will be accrued from 13 Chinese institutions in two years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are 5-year overall survival, proportion of patients who complete the postoperative chemotherapy and incidence of adverse events. Ethic and dissemination： The trial has been approved by the institutional review board of each participating institution and it was activated on December, 2016. The enrollment will be finished in December, 2018. Patient＇s follow-up will be ended until December, 2023. Trial registration： ClinicalTrials.gov, identifier： NCT02867839. Registered on August 4, 2016.展开更多
As a third generation light source, Shanghai Synchrotron Radiation Facility (SSRF) has up to 140 beam position monitors (BPM) installed to monitor the beam dynamics on its storage ring. Once the operation mode is chos...As a third generation light source, Shanghai Synchrotron Radiation Facility (SSRF) has up to 140 beam position monitors (BPM) installed to monitor the beam dynamics on its storage ring. Once the operation mode is chosen, the betatron functions are determined. Since the sinusoidal betatron oscillation is the dominant component of the transverse motion, these BPMs can be used to measure the motion to get the betatron functions. Three methods are compared to calculate the phase advance among the BPMs in this paper, aiming to find one or more feasible ways to check the beam optics in SSRF. Some experiments have also been made to verify the practicality of the phase information.展开更多
Oscillatory behaviors can be ubiquitously observed in various systems. Biological rhythms are significant in governing living activities of all units. The emergence of biological rhythms is the consequence of large nu...Oscillatory behaviors can be ubiquitously observed in various systems. Biological rhythms are significant in governing living activities of all units. The emergence of biological rhythms is the consequence of large numbers of units. In this paper we discuss several important examples of sustained oscillations in biological media, where the unit composed in the system does not possess the oscillation behavior. The dominant phase-advanced driving method is applied to study the skeletons and oscillatory organizing motifs in excitable networks and gene regulatory networks.展开更多
Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-...Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-PD-L1/TGF-βRII fusion protein)plus AG in this population(NCT04624217).In phase 1b part,the recommended dose of SHR-1701 was identified as 30 mg/kg every 3 weeks,when combined with AG.In phase 2 part,the primary endpoint was objective response rate(ORR).As of Mar 31,2023,56 patients were enrolled.Median follow-up was 10.3 months(range,0.2–24.7).ORR was 32.1%(95%CI,20.3–46.0).Median progressive-free survival(PFS)was 5.6 months(95%CI,4.3–6.6),and median overall survival(OS)was 10.3 months(95%CI,8.8–12.3).Treatment-related adverse events of grade≥3 were reported in 27(48.2%)patients,with the most common being decreased neutrophil count.Patients with PD-L1 TPS≥1%showed a higher ORR(66.7%vs.25.0%),as well as extended median PFS(6.3 vs.5.3 months)and median OS(18.8 vs.9.9 months).Additionally,reduction of CA19-9 by at least 80%during treatment and pSMAD2/3 staining intensity of 1+at baseline were potential monitoring tools and predictive biomarkers for better clinical outcomes,respectively.Tumor-specific T-cell infiltration and pancreatic cancer tumor subtypes were associated with anti-tumor response.The interactions within tumor microenvironment were involved disease progression.Overall,first-line SHR-1701 plus AG showed promising anti-tumor activity and controllable safety in advanced or metastatic pancreatic ductal adenocarcinoma,and features of patients more likely to benefit from the combination were drawn.展开更多
Taking Au?Cu system as an example, three discoveries and two methods were presented. First, a new way for boosting sustainable progress of systematic metal materials science (SMMS) and alloy gene engineering (AGE) is ...Taking Au?Cu system as an example, three discoveries and two methods were presented. First, a new way for boosting sustainable progress of systematic metal materials science (SMMS) and alloy gene engineering (AGE) is to establish holographic alloy positioning design (HAPD) system, of which the base consists of measurement and calculation center, SMMS center, AGE center, HAPD information center and HAPD cybernation center; Second, the resonance activating-sychro alternating mechanism of atom movement may be divided into the located and oriented diffuse modes; Third, the equilibrium and subequilibrium holographic network phase diagrams are blueprints and operable platform for researchers to discover, design, manufacture and deploy advanced alloys, which are obtained respectively by the equilibrium lever numerical method and cross point numerical method of isothermal Gibbs energy curves. As clicking each network point, the holographic information of three structure levels for the designed alloy may be readily obtained: the phase constitution and fraction, phase arranging structure and properties of organization; the composition, alloy gene arranging structure and properties of each phase and the electronic structures and properties of alloy genes. It will create a new era for network designing advanced alloys.展开更多
This phase Ⅲ trial aimed to compare ARX788,a site-specific,construct-homogeneous antibody-drug conjugate,with lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2(HER2)-positive advan...This phase Ⅲ trial aimed to compare ARX788,a site-specific,construct-homogeneous antibody-drug conjugate,with lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2(HER2)-positive advanced breast cancer(ABC)who had progressed on one line of trastuzumab based regimen.Eligible patients were randomized(1:1)to receive ARX788(1.5 mg/kg,IV,Q3W)or lapatinib plus capecitabine(LC:lapatinib 1250 mg QD;capecitabine 1000 mg/m^(2) BID,days 1-14,Q3W)and stratified by prior chemotherapy lines(0-1 versus>1)and visceral metastasis(yes versus no).The primary outcome was progression-free survival(PFS)assessed by a blinded independent central review(BICR).A total of 441 patients were randomly assigned to receive either ARX788(n=221)or LC(n=220).The median PFS was 11.3(95%confidence interval[CI],8.4-13.8)months with ARX788 compared with 8.2(95%CI,6.9-8.7)months with LC,as per BICR(hazard ratio[HR]0.64,p=0.0006).Frequencies of treatment-related adverse events(TRAEs)of any grade were 98.6%and 99.1%for ARX788 and LC,respectively.Grade≥3 TRAEs were 41.4%and 40.0%,respectively,the most common adverse events were blurred vision(12.3%),dry eye(9.1%),keratopathy(5.9%),and interstitial lung disease(ILD,5.9%)with ARX788;hand-foot syndrome(18.1%)and hypokalemia(5.1%)with LC;all the hematological and gastrointestinal events of grade≥3 with ARX788 were less than 3%.Six treatment-related deaths occurred,with three cases possibly related to ILD.ARX788 significantly improved PFS compared with LC in patients with HER2-positive ABC with a distinct toxicity profile,supporting it as a potential treatment option.展开更多
Pancreatic ductal adenocarcinoma(PDAC)has a poor prognosis and limited first-line treatments.This phaseⅠb/Ⅱrandomized trial(NCT05218889)investigated the efficacy and safety of surufatinib plus camrelizumab and nab-p...Pancreatic ductal adenocarcinoma(PDAC)has a poor prognosis and limited first-line treatments.This phaseⅠb/Ⅱrandomized trial(NCT05218889)investigated the efficacy and safety of surufatinib plus camrelizumab and nab-paclitaxel/S-1(NASCA)versus nab-paclitaxel and gemcitabine in patients with locally advanced or metastatic PDAC.The primary endpoints were dose-limiting toxicities and the recommended phaseⅡdose(RP2D)of surufatinib in phase lb,and the objective response rate(ORR)in phaseⅡ.PhaseⅠb used a 3+3 dose-escalation design to determine the RP2D of surufatinib in six patients,which was established at 200 mg.In phaseⅡ,patients were randomized 1∶1 to receive the NASCA(45 patients)or nab-paclitaxel and gemcitabine(45 patients).NASCA group showed an ORR of 51.1%(23/45)versus 24.4%(11/45)in the nab-paclitaxel and gemcitabine group(odds ratio 3.2,95%CI 1.3-8.2,p=0.01).The median progression-free survival(PFS)was 7.9 vs.5.3 months(HR 0.63,95%CI 0.40-0.99,p=0.045).The median overall survival was 13.0 vs.11.0 months(HR 0.77,95%CI 0.47-1.28,p=0.318).The most common Grade≥3 treatment-related adverse event was decreased neutrophil count(33.3%vs.35.6%).In the NASCA group,enrichment of CD8+and CD8+PD-1+cells,a high baseline M1/M2 macrophage ratio,and a reduction in CA19-9 levels at weeks 6 and 12 were associated with improved PFS compared to patients without these features.The NASCA regimen showed promising efficacy with tolerable safety relative to nab-paclitaxel and gemcitabine for locally advanced or metastatic PDAC.展开更多
To evaluate the efficacy and safety of KN026,a novel bispecific HER2(ECD2 and ECD4)antibody,plus KN046,a PD-L1,and CTLA4 bispecific antibody,in patients with advanced HER2-positive solid tumors.We conducted two sequen...To evaluate the efficacy and safety of KN026,a novel bispecific HER2(ECD2 and ECD4)antibody,plus KN046,a PD-L1,and CTLA4 bispecific antibody,in patients with advanced HER2-positive solid tumors.We conducted two sequentially designed phase Ib and Il studies with similar target populations and evaluation schedules.The primary endpoints included safety,maximum tolerated dose(MTD),the recommended phase Il dose(RP2D)for the phase Ib study,and the objective response rate(ORR)and duration of response(DoR)for the phase llstudy.Hereby,we solely report the results from 113 nonbreast cancer patients.In phase Ib,MTD was not reached.Dose 3 was confirmed to be acceptable for the phase lIl study.An objective response has been exclusively observed in HER2-positive patients.Any grade treatment-related adverse events(TRAEs)were reported in 108(95.6%)patients.The most common TRAEs were infusion reactions(38.9%),anemia(37.2%),elevated AST(31.0%),and diarrhea(30.1%).Among the 108 patients evaluated for efficacy,the overall ORR was 55.6%(95%Cl,45.7%,65.1%).In the HER2-positive GC subgroup,38 patients received this regimen as the 1st-line treatment and 30 patients achieved an objective response,with an ORR of 78.9%(95%Cl,62.7%,90.4%).Among 27 pretreated patients,the ORR was 44.4%(95%Cl,25.5%,64.7%).In the other HER2-positive solid tumor subgroup(n=34),the ORR was 52.9%(95%CI 35.1%,70.2%).Thus,KN026 plus KN04 exhibits promising efficacy and acceptable safety profiles in HER2-positive nonbreast cancer,as does the 1st-line treatment for GC.展开更多
Because of the special topography and large tidal range in the South Yellow Sea,the dynamic process of tide and storm surge is very complicated.The shallow water circulation model Advanced Circulation(ADCIRC)was used ...Because of the special topography and large tidal range in the South Yellow Sea,the dynamic process of tide and storm surge is very complicated.The shallow water circulation model Advanced Circulation(ADCIRC)was used to simulate the storm surge process during typhoon Winnie,Prapiroon,and Damrey,which represents three types of tracks attacking the South Yellow Sea,which are,moving northward after landing,no landing but active in offshore areas,and landing straightly to the coastline.Numerical experiments were carried out to investigate the effects of tidal phase on the tide-surge interaction as well as storm surge.The results show that the peak surge caused by Winnie and Prapiroon occurs 2-5 h before the high tide and its occurring time relative to high tide has little change with tidal phase variations.On the contrary,under the action of Damrey,the occurring time of the peak surge relative to high tide varies with tidal phase.The variation of tide-surge interaction is about 0.06-0.37 m,and the amplitude variations of interaction are smooth when tidal phase changes for Typhoon Winnie and Prapiroon.While the interaction is about 0.07-0.69 m,and great differences exists among the stations for Typhoon Damrey.It can be concluded that the tide-surge interaction of the former is dominated by the tidal phase modulation,and the time of surge peak is insensitive to the tidal phase variation.While the interaction of the latter is dominated by storm surge modulation due to the water depth varying with tide,the time of surge peak is significantly affected by tidal phase.Therefore,influence of tidal phase on storm surge is related to typhoon tracks which may provide very useful information at the design stage of coastal protection systems.展开更多
Human epidermal growth factor receptor 2(HER2)overexpression and amplification activate key pathways driving tumor progression,leading to HER2-targeted therapies.However,HER2 signaling can also be aberrantly activated...Human epidermal growth factor receptor 2(HER2)overexpression and amplification activate key pathways driving tumor progression,leading to HER2-targeted therapies.However,HER2 signaling can also be aberrantly activated by somatic mutations,independent of overexpression or amplification,contributing to tumorigenesis[1].These mutations,found in domains such as the extracellular(ECD),transmembrane(TMD)/juxtamembrane(JMD),and tyrosine kinase(KD)regions,occur across cancers,from melanoma(1%)to bladder cancer(≤12%)[1,2],suggesting a significant population could benefit from HER2-targeted treatments.Neratinib,an irreversible pan-HER tyrosine kinase inhibitor,has shown efficacy in HER2-mutated cancers and is recommended in National Comprehensive Cancer Network guidelines[3].However,resistance mechanisms,such as secondary HER2 mutations or amplifications,may limit its efficacy[4,5],highlighting the need for combination therapies.展开更多
This is an investigator-initiated,open-label,single-arm,phase Ⅱ trial that aimed to assess the combination of sintilimab plus anlotinib among patients with treatment-naïve metastatic colorectal cancer(mCRC)(APIC...This is an investigator-initiated,open-label,single-arm,phase Ⅱ trial that aimed to assess the combination of sintilimab plus anlotinib among patients with treatment-naïve metastatic colorectal cancer(mCRC)(APICAL-CRC ClinicalTrials.gov number,NCT04271813).Between June 2020 and September 2023,a total of 30 patients were eventually enrolled and received the study regimen.Among these 30 patients,50%had an Eastern Cooperative Oncology Group(ECOG)score of 0–1,and the other 50%had a score of 2.The objective response rates(ORRs)were 48.3%(95%CI 29.4–67.5)in the efficacy-evaluable cohort and 46.7%(95%CI 28.3–65.7)in the intent-to-treat(ITT)cohort.Twelve patients had stable disease,and the disease control rates(DCRs)were 89.7%(95%CI 72.6–97.8)and 86.7%(95%CI 69.3–96.2)in the efficacy-evaluable and ITT cohorts,respectively.The median progressionfree survival(mPFS)was 8.6 months(95%CI 4.8–11.0),and the median overall survival(mOS)reached 22.9 months(95%CI 13.5–36.3).Treatment-related adverse events(TRAEs)of any grade were reported in 23 patients(76.7%),and grade 3 TRAEs occurred in 4 patients(13.3%).Multivariate Cox regression analysis revealed that the presence of liver metastases was an independent prognostic factor for poor PFS(HR=5.66,95%CI 1.58–20.2)and OS(HR=7.85,95%CI 1.38–44.8),whereas FLT mutation was independently associated with poor OS(HR=12.5,95%CI 1.54–101).This trial demonstrated that sintilimab plus anlotinib exhibited promising antitumor efficacy along with a manageable safety profile among treatment-naïve mCRC patients.展开更多
The relationship between the tensile properties and S(delta) phase precipitation in cast alloy IN625 was investigated in this paper. Although the influences of δ phase on the mechanical properties have been pointed o...The relationship between the tensile properties and S(delta) phase precipitation in cast alloy IN625 was investigated in this paper. Although the influences of δ phase on the mechanical properties have been pointed out in our previous work, the relationship is still not directly determined due to the coexistence of γ"(gamma double prime) and δ precipitates. In order to exclude the effect from γ" phase, various fractions of δ precipitates with few γ" precipitates were obtained by a set of experimental alloys aging at 750 ℃, and tensile tests were conducted in parallel. The results showed that both yield strength and ultimate tensile strength increased nearly in linear with increasing δ phase fraction, while the elongation was relatively and limitedly affected by δ precipitation when the area fraction of δ phase was above 10%.展开更多
Solid-state phase transformation is usually associated with excellent mechanical properties in steel materials.A deep understanding of the formation and evolution of phase structure is essential to tailor their servic...Solid-state phase transformation is usually associated with excellent mechanical properties in steel materials.A deep understanding of the formation and evolution of phase structure is essential to tailor their service performance.As a powerful tool for capturing the evolution of complex microstructures,phase-field simulation quantitatively calculates the phase structures evolution without explicit assumptions about transient microstructures.With the development of advanced numerical technology and computing ability,phase-field methods have been successfully applied to solid-state phase transformation in steels and greatly support the research and development of advanced steel materials.The phase-field simulations of solid-phase transformation in steels were summarized,and the future development was proposed.展开更多
The China Advanced Research Reactor (CARR) is scheduled to be operated in the autumn of 2008.In this paper,we report preparations for installing the neutron radiography instrument (NRI) and for utilizing it efficientl...The China Advanced Research Reactor (CARR) is scheduled to be operated in the autumn of 2008.In this paper,we report preparations for installing the neutron radiography instrument (NRI) and for utilizing it efficiently. The 2-D relative neutron intensity profiles for the water-vapor two-phase flow inside the robe were obtained using the MCNP code without influence of y-ray and electronic-noise.The MCNP simulation of the 2-D neutron intensity profile for the water-vapor two-phase flow was demonstrated.The simulated 2-D neutron intensity profiles could be used as the benchmark data base by calibrating part of the data measured by the CARR-NRI.The 3-D objective images allow us to understand the flow pattern more clearly and it is reconstructed using the MATLAB through the threshold transformation techniques.And thus it is concluded that the MCNP code and the MATLAB are very useful for constructing the benchmark data base for the investigation of the water-vapor two-phase flow using the CARR-NRI.展开更多
文摘Synchronous reluctance motors(SynRM)are widely employed in industrial applications due to their high robustness,low cost,and absence of permanent magnets.In recent years,significant research efforts have focused on improving the controllability and efficiency of SynRM.Accurate rotor position information is essential for the controller to generate appropriate current and voltage references corresponding to the desired speed and load torque.Shaft-mounted position sensors are generally undesirable because of their high cost,sensitivity to harsh operating conditions,maintenance requirements,and reduced reliability in environments characterized by high vibration.Consequently,sensorless control techniques that estimate rotor position using measured stator currents and voltages have attracted increasing attention.However,magnetic saturation,parameter nonlinearities,and cross-coupling effects significantly degrade position estimation accuracy and may compromise the stability of sensorless SynRM drives.In this paper,a nonlinear SynRM model is developed using finite element analysis(FEA)to accurately capture magnetic saturation and cross-coupling effects,thereby providing a precise representation of the machine’s electromagnetic behavior under varying load and flux conditions.A series of magnetostatic FEA simulations is performed.To reduce computational complexity,only one motor pole is analyzed by applying anti-periodic boundary conditions along the domain sides and enforcing a zero magnetic vector potential on the external stator boundary.Nonlinear iron material properties are modeled using the appropriate B-H curve.The simulations are carried out by imposing d-and q-axis current components and computing the corresponding flux linkages and electromagnetic torque.Based on these results,both apparent and incremental inductances are extracted and incorporated into the control algorithm.An advanced fictitious flux linkage method combined with a phase-locked loop(PLL)is employed for accurate rotor position estimation.Simulation results confirm that the proposed sensorless control strategy ensures stable operation and high position estimation accuracy over the entire speed range.
基金supported by the National Science Foundation of China (No. 81374016 and 81402308)Beijing Municipal Science & Technology Commission (No. D141100000414002)
文摘Background： The ACTS-GC study had shown postoperative adiuvant therapy with S-1 improved survival of patients with locally advanced gastric cancer. Addition of oxaliplatin to S-1 is considered to be acceptable as one of the treatment options for gastric cancer patients after radical gastrectomy with D2 lymph node excision. Methods： We have commenced a randomized phase III trial in December 2016 to evaluate S-I plus oxaliplatin compared with S-1 alone in the adjuvant setting for locally advanced gastric cancer. A total of 564 patients will be accrued from 13 Chinese institutions in two years. The primary endpoint is 3-year relapse-free survival. The secondary endpoints are 5-year overall survival, proportion of patients who complete the postoperative chemotherapy and incidence of adverse events. Ethic and dissemination： The trial has been approved by the institutional review board of each participating institution and it was activated on December, 2016. The enrollment will be finished in December, 2018. Patient＇s follow-up will be ended until December, 2023. Trial registration： ClinicalTrials.gov, identifier： NCT02867839. Registered on August 4, 2016.
基金Supported by National Natural Science Foundation of China (No.11075198)
文摘As a third generation light source, Shanghai Synchrotron Radiation Facility (SSRF) has up to 140 beam position monitors (BPM) installed to monitor the beam dynamics on its storage ring. Once the operation mode is chosen, the betatron functions are determined. Since the sinusoidal betatron oscillation is the dominant component of the transverse motion, these BPMs can be used to measure the motion to get the betatron functions. Three methods are compared to calculate the phase advance among the BPMs in this paper, aiming to find one or more feasible ways to check the beam optics in SSRF. Some experiments have also been made to verify the practicality of the phase information.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11475022 and 11675001)the Scientific Research Funds of Huaqiao University,China(Grant No.15BS401)
文摘Oscillatory behaviors can be ubiquitously observed in various systems. Biological rhythms are significant in governing living activities of all units. The emergence of biological rhythms is the consequence of large numbers of units. In this paper we discuss several important examples of sustained oscillations in biological media, where the unit composed in the system does not possess the oscillation behavior. The dominant phase-advanced driving method is applied to study the skeletons and oscillatory organizing motifs in excitable networks and gene regulatory networks.
文摘Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-PD-L1/TGF-βRII fusion protein)plus AG in this population(NCT04624217).In phase 1b part,the recommended dose of SHR-1701 was identified as 30 mg/kg every 3 weeks,when combined with AG.In phase 2 part,the primary endpoint was objective response rate(ORR).As of Mar 31,2023,56 patients were enrolled.Median follow-up was 10.3 months(range,0.2–24.7).ORR was 32.1%(95%CI,20.3–46.0).Median progressive-free survival(PFS)was 5.6 months(95%CI,4.3–6.6),and median overall survival(OS)was 10.3 months(95%CI,8.8–12.3).Treatment-related adverse events of grade≥3 were reported in 27(48.2%)patients,with the most common being decreased neutrophil count.Patients with PD-L1 TPS≥1%showed a higher ORR(66.7%vs.25.0%),as well as extended median PFS(6.3 vs.5.3 months)and median OS(18.8 vs.9.9 months).Additionally,reduction of CA19-9 by at least 80%during treatment and pSMAD2/3 staining intensity of 1+at baseline were potential monitoring tools and predictive biomarkers for better clinical outcomes,respectively.Tumor-specific T-cell infiltration and pancreatic cancer tumor subtypes were associated with anti-tumor response.The interactions within tumor microenvironment were involved disease progression.Overall,first-line SHR-1701 plus AG showed promising anti-tumor activity and controllable safety in advanced or metastatic pancreatic ductal adenocarcinoma,and features of patients more likely to benefit from the combination were drawn.
基金Project(51071181)supported by the National Natural Science Foundation of ChinaProject(2013FJ4043)supported by the Natural Science Foundation of Hunan Province,China
文摘Taking Au?Cu system as an example, three discoveries and two methods were presented. First, a new way for boosting sustainable progress of systematic metal materials science (SMMS) and alloy gene engineering (AGE) is to establish holographic alloy positioning design (HAPD) system, of which the base consists of measurement and calculation center, SMMS center, AGE center, HAPD information center and HAPD cybernation center; Second, the resonance activating-sychro alternating mechanism of atom movement may be divided into the located and oriented diffuse modes; Third, the equilibrium and subequilibrium holographic network phase diagrams are blueprints and operable platform for researchers to discover, design, manufacture and deploy advanced alloys, which are obtained respectively by the equilibrium lever numerical method and cross point numerical method of isothermal Gibbs energy curves. As clicking each network point, the holographic information of three structure levels for the designed alloy may be readily obtained: the phase constitution and fraction, phase arranging structure and properties of organization; the composition, alloy gene arranging structure and properties of each phase and the electronic structures and properties of alloy genes. It will create a new era for network designing advanced alloys.
文摘This phase Ⅲ trial aimed to compare ARX788,a site-specific,construct-homogeneous antibody-drug conjugate,with lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2(HER2)-positive advanced breast cancer(ABC)who had progressed on one line of trastuzumab based regimen.Eligible patients were randomized(1:1)to receive ARX788(1.5 mg/kg,IV,Q3W)or lapatinib plus capecitabine(LC:lapatinib 1250 mg QD;capecitabine 1000 mg/m^(2) BID,days 1-14,Q3W)and stratified by prior chemotherapy lines(0-1 versus>1)and visceral metastasis(yes versus no).The primary outcome was progression-free survival(PFS)assessed by a blinded independent central review(BICR).A total of 441 patients were randomly assigned to receive either ARX788(n=221)or LC(n=220).The median PFS was 11.3(95%confidence interval[CI],8.4-13.8)months with ARX788 compared with 8.2(95%CI,6.9-8.7)months with LC,as per BICR(hazard ratio[HR]0.64,p=0.0006).Frequencies of treatment-related adverse events(TRAEs)of any grade were 98.6%and 99.1%for ARX788 and LC,respectively.Grade≥3 TRAEs were 41.4%and 40.0%,respectively,the most common adverse events were blurred vision(12.3%),dry eye(9.1%),keratopathy(5.9%),and interstitial lung disease(ILD,5.9%)with ARX788;hand-foot syndrome(18.1%)and hypokalemia(5.1%)with LC;all the hematological and gastrointestinal events of grade≥3 with ARX788 were less than 3%.Six treatment-related deaths occurred,with three cases possibly related to ILD.ARX788 significantly improved PFS compared with LC in patients with HER2-positive ABC with a distinct toxicity profile,supporting it as a potential treatment option.
基金supported by Chinese National Natural Science Foundation Project(82272643)Beijing Natural Science Foundation Project(7232163,7252130).
文摘Pancreatic ductal adenocarcinoma(PDAC)has a poor prognosis and limited first-line treatments.This phaseⅠb/Ⅱrandomized trial(NCT05218889)investigated the efficacy and safety of surufatinib plus camrelizumab and nab-paclitaxel/S-1(NASCA)versus nab-paclitaxel and gemcitabine in patients with locally advanced or metastatic PDAC.The primary endpoints were dose-limiting toxicities and the recommended phaseⅡdose(RP2D)of surufatinib in phase lb,and the objective response rate(ORR)in phaseⅡ.PhaseⅠb used a 3+3 dose-escalation design to determine the RP2D of surufatinib in six patients,which was established at 200 mg.In phaseⅡ,patients were randomized 1∶1 to receive the NASCA(45 patients)or nab-paclitaxel and gemcitabine(45 patients).NASCA group showed an ORR of 51.1%(23/45)versus 24.4%(11/45)in the nab-paclitaxel and gemcitabine group(odds ratio 3.2,95%CI 1.3-8.2,p=0.01).The median progression-free survival(PFS)was 7.9 vs.5.3 months(HR 0.63,95%CI 0.40-0.99,p=0.045).The median overall survival was 13.0 vs.11.0 months(HR 0.77,95%CI 0.47-1.28,p=0.318).The most common Grade≥3 treatment-related adverse event was decreased neutrophil count(33.3%vs.35.6%).In the NASCA group,enrichment of CD8+and CD8+PD-1+cells,a high baseline M1/M2 macrophage ratio,and a reduction in CA19-9 levels at weeks 6 and 12 were associated with improved PFS compared to patients without these features.The NASCA regimen showed promising efficacy with tolerable safety relative to nab-paclitaxel and gemcitabine for locally advanced or metastatic PDAC.
基金supported by the National Natural Science Foundation of China(91959205 to L.S.)the Natural Science Foundation of Beijing Municipality(Z200015 to X.T.Z).
文摘To evaluate the efficacy and safety of KN026,a novel bispecific HER2(ECD2 and ECD4)antibody,plus KN046,a PD-L1,and CTLA4 bispecific antibody,in patients with advanced HER2-positive solid tumors.We conducted two sequentially designed phase Ib and Il studies with similar target populations and evaluation schedules.The primary endpoints included safety,maximum tolerated dose(MTD),the recommended phase Il dose(RP2D)for the phase Ib study,and the objective response rate(ORR)and duration of response(DoR)for the phase llstudy.Hereby,we solely report the results from 113 nonbreast cancer patients.In phase Ib,MTD was not reached.Dose 3 was confirmed to be acceptable for the phase lIl study.An objective response has been exclusively observed in HER2-positive patients.Any grade treatment-related adverse events(TRAEs)were reported in 108(95.6%)patients.The most common TRAEs were infusion reactions(38.9%),anemia(37.2%),elevated AST(31.0%),and diarrhea(30.1%).Among the 108 patients evaluated for efficacy,the overall ORR was 55.6%(95%Cl,45.7%,65.1%).In the HER2-positive GC subgroup,38 patients received this regimen as the 1st-line treatment and 30 patients achieved an objective response,with an ORR of 78.9%(95%Cl,62.7%,90.4%).Among 27 pretreated patients,the ORR was 44.4%(95%Cl,25.5%,64.7%).In the other HER2-positive solid tumor subgroup(n=34),the ORR was 52.9%(95%CI 35.1%,70.2%).Thus,KN026 plus KN04 exhibits promising efficacy and acceptable safety profiles in HER2-positive nonbreast cancer,as does the 1st-line treatment for GC.
基金Supported by the National Key Research and Development Program of China(No.2016YFC1402000)
文摘Because of the special topography and large tidal range in the South Yellow Sea,the dynamic process of tide and storm surge is very complicated.The shallow water circulation model Advanced Circulation(ADCIRC)was used to simulate the storm surge process during typhoon Winnie,Prapiroon,and Damrey,which represents three types of tracks attacking the South Yellow Sea,which are,moving northward after landing,no landing but active in offshore areas,and landing straightly to the coastline.Numerical experiments were carried out to investigate the effects of tidal phase on the tide-surge interaction as well as storm surge.The results show that the peak surge caused by Winnie and Prapiroon occurs 2-5 h before the high tide and its occurring time relative to high tide has little change with tidal phase variations.On the contrary,under the action of Damrey,the occurring time of the peak surge relative to high tide varies with tidal phase.The variation of tide-surge interaction is about 0.06-0.37 m,and the amplitude variations of interaction are smooth when tidal phase changes for Typhoon Winnie and Prapiroon.While the interaction is about 0.07-0.69 m,and great differences exists among the stations for Typhoon Damrey.It can be concluded that the tide-surge interaction of the former is dominated by the tidal phase modulation,and the time of surge peak is insensitive to the tidal phase variation.While the interaction of the latter is dominated by storm surge modulation due to the water depth varying with tide,the time of surge peak is significantly affected by tidal phase.Therefore,influence of tidal phase on storm surge is related to typhoon tracks which may provide very useful information at the design stage of coastal protection systems.
基金supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)the Ministry of Health&Welfare,Republic of Korea(grant numbers:HI17C2206 and HA22C0012)+1 种基金Additional support was provided by a grant from the National R&D Program for Cancer Control,National Cancer Center(NCC),Ministry of Health&Welfare,Republic of Korea(grant number:HA22C0052)through the KOSMOS Molecular Tumor Board.
文摘Human epidermal growth factor receptor 2(HER2)overexpression and amplification activate key pathways driving tumor progression,leading to HER2-targeted therapies.However,HER2 signaling can also be aberrantly activated by somatic mutations,independent of overexpression or amplification,contributing to tumorigenesis[1].These mutations,found in domains such as the extracellular(ECD),transmembrane(TMD)/juxtamembrane(JMD),and tyrosine kinase(KD)regions,occur across cancers,from melanoma(1%)to bladder cancer(≤12%)[1,2],suggesting a significant population could benefit from HER2-targeted treatments.Neratinib,an irreversible pan-HER tyrosine kinase inhibitor,has shown efficacy in HER2-mutated cancers and is recommended in National Comprehensive Cancer Network guidelines[3].However,resistance mechanisms,such as secondary HER2 mutations or amplifications,may limit its efficacy[4,5],highlighting the need for combination therapies.
基金supported by Chinese National Natural Science Funding[grant number 82172710,2021]the Shanghai Public Health Outstanding Academic Leader Program(GWVI-11.2-XD22,grant to Y.S.Z.)+4 种基金the Shanghai Oriental Talents Program(grant to Y.S.Z.)the Shanghai Municipal Health Commission Health Industry Clinical Research Project(202240277,grant to Z.W.20224Y0077,grant to B.D.Q.)the Innovation Clinical Research Project of Shanghai Changzheng Hospital[grant number 2020YLCYJ-Z03,2020grant number 2023YJBF-FH05,2023].
文摘This is an investigator-initiated,open-label,single-arm,phase Ⅱ trial that aimed to assess the combination of sintilimab plus anlotinib among patients with treatment-naïve metastatic colorectal cancer(mCRC)(APICAL-CRC ClinicalTrials.gov number,NCT04271813).Between June 2020 and September 2023,a total of 30 patients were eventually enrolled and received the study regimen.Among these 30 patients,50%had an Eastern Cooperative Oncology Group(ECOG)score of 0–1,and the other 50%had a score of 2.The objective response rates(ORRs)were 48.3%(95%CI 29.4–67.5)in the efficacy-evaluable cohort and 46.7%(95%CI 28.3–65.7)in the intent-to-treat(ITT)cohort.Twelve patients had stable disease,and the disease control rates(DCRs)were 89.7%(95%CI 72.6–97.8)and 86.7%(95%CI 69.3–96.2)in the efficacy-evaluable and ITT cohorts,respectively.The median progressionfree survival(mPFS)was 8.6 months(95%CI 4.8–11.0),and the median overall survival(mOS)reached 22.9 months(95%CI 13.5–36.3).Treatment-related adverse events(TRAEs)of any grade were reported in 23 patients(76.7%),and grade 3 TRAEs occurred in 4 patients(13.3%).Multivariate Cox regression analysis revealed that the presence of liver metastases was an independent prognostic factor for poor PFS(HR=5.66,95%CI 1.58–20.2)and OS(HR=7.85,95%CI 1.38–44.8),whereas FLT mutation was independently associated with poor OS(HR=12.5,95%CI 1.54–101).This trial demonstrated that sintilimab plus anlotinib exhibited promising antitumor efficacy along with a manageable safety profile among treatment-naïve mCRC patients.
基金financially supported by the National Key Research and Development Program of China (No. 2017YFB0305204)the National Natural Science Foundation of China (No. 51571191)
文摘The relationship between the tensile properties and S(delta) phase precipitation in cast alloy IN625 was investigated in this paper. Although the influences of δ phase on the mechanical properties have been pointed out in our previous work, the relationship is still not directly determined due to the coexistence of γ"(gamma double prime) and δ precipitates. In order to exclude the effect from γ" phase, various fractions of δ precipitates with few γ" precipitates were obtained by a set of experimental alloys aging at 750 ℃, and tensile tests were conducted in parallel. The results showed that both yield strength and ultimate tensile strength increased nearly in linear with increasing δ phase fraction, while the elongation was relatively and limitedly affected by δ precipitation when the area fraction of δ phase was above 10%.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.52071023,51901013,and 52122408)H.H.Wu also thanks to the financial support from the Fundamental Research Funds for the Central Universities(University of Science and Technology Beijing,Nos.FRF-TP-2021-04C1 and 06500135).
文摘Solid-state phase transformation is usually associated with excellent mechanical properties in steel materials.A deep understanding of the formation and evolution of phase structure is essential to tailor their service performance.As a powerful tool for capturing the evolution of complex microstructures,phase-field simulation quantitatively calculates the phase structures evolution without explicit assumptions about transient microstructures.With the development of advanced numerical technology and computing ability,phase-field methods have been successfully applied to solid-state phase transformation in steels and greatly support the research and development of advanced steel materials.The phase-field simulations of solid-phase transformation in steels were summarized,and the future development was proposed.
基金Supported by National Natural Science Foundation of China (Grant No.50876080)
文摘The China Advanced Research Reactor (CARR) is scheduled to be operated in the autumn of 2008.In this paper,we report preparations for installing the neutron radiography instrument (NRI) and for utilizing it efficiently. The 2-D relative neutron intensity profiles for the water-vapor two-phase flow inside the robe were obtained using the MCNP code without influence of y-ray and electronic-noise.The MCNP simulation of the 2-D neutron intensity profile for the water-vapor two-phase flow was demonstrated.The simulated 2-D neutron intensity profiles could be used as the benchmark data base by calibrating part of the data measured by the CARR-NRI.The 3-D objective images allow us to understand the flow pattern more clearly and it is reconstructed using the MATLAB through the threshold transformation techniques.And thus it is concluded that the MCNP code and the MATLAB are very useful for constructing the benchmark data base for the investigation of the water-vapor two-phase flow using the CARR-NRI.
