With the advancement of computer and mathematical techniques,significant progress has been made in the 3D modeling of foundation piles.Existing methods include the 3D semi-analytical model for non-destructive low-stra...With the advancement of computer and mathematical techniques,significant progress has been made in the 3D modeling of foundation piles.Existing methods include the 3D semi-analytical model for non-destructive low-strain integrity assessment of large-diameter thin-walled pipe piles and the 3D soil-pile dynamic interaction model.However,these methods have complex analysis procedures and substantial limitations.This paper introduces an innovative and streamlined 3D imaging technique tailored for the detection of pile damage.The approach harnesses the power of an eight-channel ring array transducer to capture internal reflection signals within foundation piles.The acquired signals are subsequently processed using the Hilbert-Huang Transform(HHT),a robust analytical tool known for its effectiveness in handling non-stationary signals.Through the development of a sophisticated multi-channel ring array imaging algorithm,this technique empowers engineers and researchers to identify various pile defects,including their specific type,precise location,and obtain detailed 3D imaging representations.The findings of this research offer a valuable blend of theoretical insights and practical guidance,significantly advancing the state-of-the-art in the realm of concrete pile integrity inspection.By simplifying and enhancing the assessment process,this innovative approach not only addresses the complexities of existing methods but also contributes to the overall safety and reliability of concrete engineering structures.展开更多
Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the...Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.展开更多
Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time ...Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.展开更多
Li metal is considered an ideal anode material because of its high theoretical capacity and low electrode potential.However,the practical usage of Li metal as an anode is severely limited because of inevitable parasit...Li metal is considered an ideal anode material because of its high theoretical capacity and low electrode potential.However,the practical usage of Li metal as an anode is severely limited because of inevitable parasitic side reactions with electrolyte and dendrites formation.At present,single-component artificial solid electrolyte interphase cannot simultaneously meet the multiple functions of promoting ion conduction,guiding lithium ion deposition,inhibiting dendrite growth,and reducing interface side reactions.Therefore,multi-component design on Li metal surface is widely investigated to achieve long-term cycling.Herein,we report a Li_(2)Ga-carbonate polymer interphase layer to solve volume changes,Li dendrites formation and side-reactions.As a result,the Li symmetric cell can be stabilized at 3.0 m A/cm^(2)in carbonate electrolyte with limited volume of 20μL.Coupled with 13.6 mg/cm^(2)(loading of 2 mAh/cm^(2))LiFePO_(4)cathode,discharge capacity retains at 90%for over 150 cycles under limited electrolyte conditions.With such an alloy-polymer interphase layer,higher energy density Li metal batteries become prominent in the near future.展开更多
The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author af...The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author affliction and responded with the correct by the time this erratum is being published.展开更多
Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our stud...Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our study aimed to find the evolution and genotypic characteristic of SCLC transformation.Methods:Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer(NSCLC)patients were included.Whole exome sequencing(WES)of both primary and transformed re-biopsy lesions was conducted on 12 patients.Clinical characteristics were analyzed using R software(v.3.6.1).Results:Our study included 31 patients,of whom,three had lung squamous cell carcinoma,6 patients did not carry EGFR mutations,and 30 patients received chemotherapy for SCLCs.The disease control rate(DCR)was 96.7%,and the median progression-free survival(PFS)was 4.03 months.The median time to transformation was 33.07 months,and the median overall survival(OS)was 62.08 months.Somatic mutation analysis showed that besides TP53,RB1,and EGFR,there was a high occurrence of mutations to CSMD3 and ADAMTS19,espe-cially in the EGFR-wild type(EGFR-wt)group.Concerning mutational signature,the EGFR-mutant(EGFR-mut)transformed group favored an apolipoprotein B(APOBEC)mRNA editing catalytic polypeptide-like-associated mutation pattern(P=0.16).DNA damage repair(DDR)-related signatures were significantly enriched in the EGFR-wt transformed group(P=0.034).Additionally,clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree.Transformed SCLCs are not sensitive to immunotherapy,possibly due to increased tumor heterogeneity.Conclusions:Our results indicate that the EGFR-wt patients could also transform to SCLCs,but they have different genetic features with EGFR-mut patients.SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.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,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.展开更多
Ultrasmall silver nanoclusters(Ag NCs)with rich surface chemistry and good biocompatibility are promising in antibacterial application,however,further development of Ag NCs for practical settings has been constrained ...Ultrasmall silver nanoclusters(Ag NCs)with rich surface chemistry and good biocompatibility are promising in antibacterial application,however,further development of Ag NCs for practical settings has been constrained by their relatively weak antibacterial activity.Using the nutritionally-rich medium for bacteria(e.g.,Luria-Bertani(LB)medium)to coat active Ag NCs could further improve their antibacterial activity.Here,we provide a delicate design of a highly efficient Ag NCs@ELB antibacterial agent(ELB denotes the extract of LB medium)by anchoring Ag NCs inside the ELB species via light irradiation.The as-designed Ag NCs with bacterium-favored nutrients on the surface can be easily swallowed by the bacteria,boosting the production of the intracellular reactive oxygen species(ROS,about 2-fold of that in the pristine Ag NCs).Subsequently,a higher concentration of ROS generated in Ag NCs@ELB leads to enhanced antibacterial activity,and enables to reduce the colony forming units(CFU)of both gram-positive and gram-negative bacteria with 3–4 orders of magnitude less than that treated with the pristine Ag NCs.In addition,the Ag NCs@ELB also shows good biocompatibility.This study suggests that surface engineering of active species(e.g.,Ag NCs)with nutritionally-rich medium of the bacteria is an efficient way to improve their antibacterial activity.展开更多
Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we cond...Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.展开更多
基金supported by China Scholarship Council(No.202008320084)the National Natural Science Foundation of China(Nos.11872191 and 11702118)Foreign Specialist Project of Ministry of Science and Technology(DL2022014011L).
文摘With the advancement of computer and mathematical techniques,significant progress has been made in the 3D modeling of foundation piles.Existing methods include the 3D semi-analytical model for non-destructive low-strain integrity assessment of large-diameter thin-walled pipe piles and the 3D soil-pile dynamic interaction model.However,these methods have complex analysis procedures and substantial limitations.This paper introduces an innovative and streamlined 3D imaging technique tailored for the detection of pile damage.The approach harnesses the power of an eight-channel ring array transducer to capture internal reflection signals within foundation piles.The acquired signals are subsequently processed using the Hilbert-Huang Transform(HHT),a robust analytical tool known for its effectiveness in handling non-stationary signals.Through the development of a sophisticated multi-channel ring array imaging algorithm,this technique empowers engineers and researchers to identify various pile defects,including their specific type,precise location,and obtain detailed 3D imaging representations.The findings of this research offer a valuable blend of theoretical insights and practical guidance,significantly advancing the state-of-the-art in the realm of concrete pile integrity inspection.By simplifying and enhancing the assessment process,this innovative approach not only addresses the complexities of existing methods but also contributes to the overall safety and reliability of concrete engineering structures.
基金supported by the Beijing Natural Science Foundation(Commission No.7162038)the Beijing Municipal Administration of Hospitals’Youth Program(Commission No.QML20161101)
文摘Objective： Although superior clinical benefits of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in the treatment of advanced non-small-cell lung cancer （NSCLC） had been reported, the survival difference between exon 19 deletion （Dell9） and exon 21 Leu858Arg substitution （L858R） remains controversial. The purpose of this study is to investigate the differences in progression-free survival （PFS） and overall survival （OS） between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. Methods： There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Dell9 group and the L858R mutated group according to their mutant subtype. Propensity score matching （PSM） was conducted by using a nearest-neighbor algorithm （1：1） to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Results： The PFS in Dell9 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Dell9 group （before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339）. The Dell9 group was significantly younger compared with the L858R mutation group in age （P=0.015）. Conclusions： No significant difference was found in the PFS or OS between the Dell9 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Dell9 and L858R groups. PSM is of important value to the elimination of potential bias.
文摘Objective: Adjuvant chemotherapy (AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer (NSCLC); however, few studies have reported the correlation between the time to initiation of AC (TTAC) and survival in NSCLC patients. Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed. TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival (DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching (PSM) was performed for survival analysis using the match data. Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A (<= 35 d) and group B (> 35 d). There was no significant difference in the DFS between the two groups (P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs (P=0.283). Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.
基金supported by Jilin Province Science and Technology Department Major Science and Technology Project(Nos.20220301004GX,20220301005GX)Key Subject Construction of Physical Chemistry of Northeast Normal University,National Natural Science Foundation of China(Nos.21905110,22102020)+2 种基金National Natural Science Foundation of China(No.21905041)Special foundation of Jilin Province Industrial technology Research and Development(No.2019C042)the Fundamental Research Funds for the Central Universities(No.2412020FZ008)。
文摘Li metal is considered an ideal anode material because of its high theoretical capacity and low electrode potential.However,the practical usage of Li metal as an anode is severely limited because of inevitable parasitic side reactions with electrolyte and dendrites formation.At present,single-component artificial solid electrolyte interphase cannot simultaneously meet the multiple functions of promoting ion conduction,guiding lithium ion deposition,inhibiting dendrite growth,and reducing interface side reactions.Therefore,multi-component design on Li metal surface is widely investigated to achieve long-term cycling.Herein,we report a Li_(2)Ga-carbonate polymer interphase layer to solve volume changes,Li dendrites formation and side-reactions.As a result,the Li symmetric cell can be stabilized at 3.0 m A/cm^(2)in carbonate electrolyte with limited volume of 20μL.Coupled with 13.6 mg/cm^(2)(loading of 2 mAh/cm^(2))LiFePO_(4)cathode,discharge capacity retains at 90%for over 150 cycles under limited electrolyte conditions.With such an alloy-polymer interphase layer,higher energy density Li metal batteries become prominent in the near future.
文摘The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author affliction and responded with the correct by the time this erratum is being published.
基金supported by the Beijing Municipal Administration of Hospitals Incubating Program(PX2019038,PX2020044)Beijing Youth Program for Outstanding Talents(2018000021469G262)+3 种基金National Key Research and Development Project(2019YFC1315700)NSFC Key Program(81630071)NSFC General Program(81871889,81972905)CAMS Key Lab of Translational Research on Lung Cancer(2018PT31035)and Aiyou Foundation(KY201701).
文摘Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our study aimed to find the evolution and genotypic characteristic of SCLC transformation.Methods:Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer(NSCLC)patients were included.Whole exome sequencing(WES)of both primary and transformed re-biopsy lesions was conducted on 12 patients.Clinical characteristics were analyzed using R software(v.3.6.1).Results:Our study included 31 patients,of whom,three had lung squamous cell carcinoma,6 patients did not carry EGFR mutations,and 30 patients received chemotherapy for SCLCs.The disease control rate(DCR)was 96.7%,and the median progression-free survival(PFS)was 4.03 months.The median time to transformation was 33.07 months,and the median overall survival(OS)was 62.08 months.Somatic mutation analysis showed that besides TP53,RB1,and EGFR,there was a high occurrence of mutations to CSMD3 and ADAMTS19,espe-cially in the EGFR-wild type(EGFR-wt)group.Concerning mutational signature,the EGFR-mutant(EGFR-mut)transformed group favored an apolipoprotein B(APOBEC)mRNA editing catalytic polypeptide-like-associated mutation pattern(P=0.16).DNA damage repair(DDR)-related signatures were significantly enriched in the EGFR-wt transformed group(P=0.034).Additionally,clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree.Transformed SCLCs are not sensitive to immunotherapy,possibly due to increased tumor heterogeneity.Conclusions:Our results indicate that the EGFR-wt patients could also transform to SCLCs,but they have different genetic features with EGFR-mut patients.SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.
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,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.
基金supported by the Taishan Scholar Foundation(No.tsqn201812074)the Young Talents Joint Fund of Shandong Province(No.ZR2019YQ07)+2 种基金the Original Innovation Project of Qingdao City(No.18-2-2-58-jch)the Open Fund of Shandong Key Laboratory of Biochemical Analysis(No.QUSTHX201901)the Ministry of Education,Singapore,Academic Research Grant R-279-000-538-114.
文摘Ultrasmall silver nanoclusters(Ag NCs)with rich surface chemistry and good biocompatibility are promising in antibacterial application,however,further development of Ag NCs for practical settings has been constrained by their relatively weak antibacterial activity.Using the nutritionally-rich medium for bacteria(e.g.,Luria-Bertani(LB)medium)to coat active Ag NCs could further improve their antibacterial activity.Here,we provide a delicate design of a highly efficient Ag NCs@ELB antibacterial agent(ELB denotes the extract of LB medium)by anchoring Ag NCs inside the ELB species via light irradiation.The as-designed Ag NCs with bacterium-favored nutrients on the surface can be easily swallowed by the bacteria,boosting the production of the intracellular reactive oxygen species(ROS,about 2-fold of that in the pristine Ag NCs).Subsequently,a higher concentration of ROS generated in Ag NCs@ELB leads to enhanced antibacterial activity,and enables to reduce the colony forming units(CFU)of both gram-positive and gram-negative bacteria with 3–4 orders of magnitude less than that treated with the pristine Ag NCs.In addition,the Ag NCs@ELB also shows good biocompatibility.This study suggests that surface engineering of active species(e.g.,Ag NCs)with nutritionally-rich medium of the bacteria is an efficient way to improve their antibacterial activity.
基金Nanjing Luye Pharmaceutical Co.Ltd,Nanjing,China,Grant/Award Number:2017ZZ02012sponsored by Nanjing Luye Pharmaceu-tical Co.Ltd,Nanjing,China,and supported in part by grants from Shanghai Key disciplines of Respiratory(No.2017ZZ02012)and Shanghai Major Diseases Multidisci-plinary Cooperation Diagnosis and Treatment Construc-tion Project.
文摘Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.
