Purpose:Many science,technology and innovation(STI)resources are attached with several different labels.To assign automatically the resulting labels to an interested instance,many approaches with good performance on t...Purpose:Many science,technology and innovation(STI)resources are attached with several different labels.To assign automatically the resulting labels to an interested instance,many approaches with good performance on the benchmark datasets have been proposed for multi-label classification task in the literature.Furthermore,several open-source tools implementing these approaches have also been developed.However,the characteristics of real-world multi-label patent and publication datasets are not completely in line with those of benchmark ones.Therefore,the main purpose of this paper is to evaluate comprehensively seven multi-label classification methods on real-world datasets.Research limitations:Three real-world datasets differ in the following aspects:statement,data quality,and purposes.Additionally,open-source tools designed for multi-label classification also have intrinsic differences in their approaches for data processing and feature selection,which in turn impacts the performance of a multi-label classification approach.In the near future,we will enhance experimental precision and reinforce the validity of conclusions by employing more rigorous control over variables through introducing expanded parameter settings.Practical implications:The observed Macro F1 and Micro F1 scores on real-world datasets typically fall short of those achieved on benchmark datasets,underscoring the complexity of real-world multi-label classification tasks.Approaches leveraging deep learning techniques offer promising solutions by accommodating the hierarchical relationships and interdependencies among labels.With ongoing enhancements in deep learning algorithms and large-scale models,it is expected that the efficacy of multi-label classification tasks will be significantly improved,reaching a level of practical utility in the foreseeable future.Originality/value:(1)Seven multi-label classification methods are comprehensively compared on three real-world datasets.(2)The TextCNN and TextRCNN models perform better on small-scale datasets with more complex hierarchical structure of labels and more balanced document-label distribution.(3)The MLkNN method works better on the larger-scale dataset with more unbalanced document-label distribution.展开更多
Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associ...Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.展开更多
The treatment duration of heat-sensitive moxibustion（approximately 40 minutes on average） is longer than that of traditional suspended moxibustion.The present study investigated expression changes of three inflammat...The treatment duration of heat-sensitive moxibustion（approximately 40 minutes on average） is longer than that of traditional suspended moxibustion.The present study investigated expression changes of three inflammatory and apoptosis-associated proteins（inducible nitric oxide synthase,cyclooxygenase-2 and caspase-3） in transient middle cerebral artery occlusion model rats following suspended moxibustion for 40 minutes,to explore the mechanisms underlying neuroprotective action of suspended moxibustion.The results indicated that suspended moxibustion at acupoint Dazhui（DU 14） for 40 minutes reduced the cortical expression of caspase-3,cyclooxygenase-2 and inducible nitric oxide synthase proteins of transient middle cerebral artery occlusion model rats,as well as decreasing infarct volume and ameliorating the neurological deficit score.Outcomes with 40 minutes of moxibustion were superior to the outcomes after suspended moxibustion for 15 minutes.展开更多
During ion cyclotron resonance heating,the sheath power dissipation caused by ion acceleration in the radio frequency(RF)sheath is one of the main causes of RF power loss in the tokamak edge region.To estimate the pow...During ion cyclotron resonance heating,the sheath power dissipation caused by ion acceleration in the radio frequency(RF)sheath is one of the main causes of RF power loss in the tokamak edge region.To estimate the power dissipation of an RF sheath in the ion cyclotron range of frequency(ICRF),a 1 D fluid model for the multi-component plasma sheath driven by a sinusoidal disturbance current in the ICRF is presented.By investigation of the sheath potential and ion flux at the wall,it is shown that the larger frequency and lower amplitude of the disturbance current can cause smaller sheath power dissipation.The effect of the energetic ion on the sheath power dissipation depends on the disturbance current.For large amplitude of disturbance current,the increase in the concentration and energy of the energetic ion leads to a decrease in sheath power dissipation.While for a small disturbance current,the sheath power dissipation demonstrates non-monotonic variation with the concentration and energy of the energetic ion.In addition,the sheath power dissipation is found to have a small increase in the presence of light impurity ions with low valence.展开更多
Sap-sucking insects often transmit plant viruses but also carry insect viruses,which infect insects but not plants.The impact of such insect viruses on insect host biology and ecology is largely unknown.Here,we identi...Sap-sucking insects often transmit plant viruses but also carry insect viruses,which infect insects but not plants.The impact of such insect viruses on insect host biology and ecology is largely unknown.Here,we identified a novel insect-specific virus carried by brown citrus aphid(Aphis citricidus),which we tentatively named Aphis citricidus picornavirus(AcPV).Phylogenetic analysis discovered a monophyletic cluster with AcPV and other unassigned viruses,suggesting that these viruses represent a new family in order Picornavirales.Systemic infection with AcPV triggered aphid antiviral immunity mediated by RNA interference,resulting in asymptomatic tolerance.Importantly,we found that AcPV was transmitted horizontally by secretion of the salivary gland into the feeding sites of plants.AcPV influenced aphid stylet behavior during feeding and increased the time required for intercellular penetration,thus promoting its transmission among aphids with plants as an intermediate site.The gene expression results suggested that this mechanism was linked with transcription of salivary protein genes and plant defense hormone signaling.Together,our results show that the horizontal transmission of AcPV in brown citrus aphids evolved in a manner similar to that of the circulative transmission of plant viruses by insect vectors,thus providing a new ecological perspective on the activity of insect-specific viruses found in aphids and improving the understanding of insect virus ecology.展开更多
Multidrug resistance(MDR) remains a major clinical obstacle to successful cancer treatment.Although diverse mechanisms of MDR have been well elucidated, such as dysregulation of drugs transporters, defects of apoptosi...Multidrug resistance(MDR) remains a major clinical obstacle to successful cancer treatment.Although diverse mechanisms of MDR have been well elucidated, such as dysregulation of drugs transporters, defects of apoptosis and autophagy machinery, alterations of drug metabolism and drug targets, disrupti on of redox homeostasis, the exact mechanisms of MDR in a specific cancer patient and the cross-talk among these different mechanisms and how they are regulated are poorly understood.Micro RNAs(mi RNAs) are a new class of small noncoding RNAs that could control the global activity of the cell by post-transcriptionally regulating a large variety of target genes and proteins expression.Accumulating evidence shows that mi RNAs play a key regulatory role in MDR through modulating various drug resistant mechanisms mentioned above, thereby holding much promise for developing novel and more effective individualized therapies for cancer treatment. This review summarizes the various MDR mechanisms and mainly focuses on the role of mi RNAs in regulating MDR in cancer treatment.展开更多
Background:Identification of activated epidermal growth factor receptor(EGFR)mutations and application of EGFR-tyrosine kinase inhibitors(EGFR-TKIs)have greatly changed the therapeutic strategies of non-small-cell lun...Background:Identification of activated epidermal growth factor receptor(EGFR)mutations and application of EGFR-tyrosine kinase inhibitors(EGFR-TKIs)have greatly changed the therapeutic strategies of non-small-cell lung cancer(NSCLC).However,the long-term efficacy of EGFR-TKI therapy is limited due to the development of drug resistance.The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR-TKIs in advanced NSCLC patients with activated EGFR mutations.Methods:We retrospectively reviewed the clinical data from 416 patients with stage III/IV or recurrent NSCLC who received an initial EGFR-TKI treatment,from April 2004 and March 2011,at the Sun Yat-sen University Cancer Center.Several genetic alterations associated with the efficacy of EGFR-TKIs,including the alterations in BIM,ALK,KRAS,PIK3CA,PTEN,MET,IGF1R,and ROS1,were detected by the routine clinical technologies.The progression-free survival(PFS)and overall survival(OS)were compared between different groups using Kaplan-Meier survival analysis with the log-rank test.A Cox regression model was used to estimate multivariable-adjusted hazard ratios(HRs)and their 95%confi-dence intervals(95%CIs)associated with the PFS and OS.Results:Among the investigated patients,169 NSCLC patients harbored EGFR-sensitive mutations.EGFR-mutant patients having PTEN deletion had a shorter PFS and OS than those with intact PTEN(P=0.003 for PFS,and P=0.034 for OS).In the combined molecular analysis of EGFR signaling pathway and resistance genes,we found that EGFR-mutant patients coexisted with aberrant alterations in EGFR signaling pathway and those having resistant genes had a statistically poorer PFS than those without such alterations(P<0.001).A Cox proportional regression model determined that PTEN deletion(HR=4.29,95%CI=1.72-10.70)and low PTEN expression(HR=1.96,95%CI=1.22-3.13),MET FISH+(HR=2.83,95%CI=1.37-5.86)were independent predictors for PFS in patients with EGFR-TKI treatment after adjustment for multiple factor.Conclusions:We determined that the coexistence of genetic alterations in cancer genes may explain primary resistance to EGFR-TKIs.展开更多
Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug ...Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.展开更多
With the aid of the bosonic mode conversions in two different coordinate frames, we show that （1） the coordinate eigenstate is exactly the EPR entangled state representation, and （2） the Laguerre-Ganssian （LG） m...With the aid of the bosonic mode conversions in two different coordinate frames, we show that （1） the coordinate eigenstate is exactly the EPR entangled state representation, and （2） the Laguerre-Ganssian （LG） mode is exactly the wave function of the common eigenvector of the orbital angular momentum and the total photon number operator. Moreover, by using the conversion of the bosonic modes, the Wigner representation of the LG mode can be obtained directly. It provides an alternative to the method of Simon and Agarwal.展开更多
Systemic RNA interference deficient-1-like(SIL1)is considered a core component in dsRNA uptake in some insect species.Investigation related to the potential function of SIL1 in dsRNA uptake can contribute to a further...Systemic RNA interference deficient-1-like(SIL1)is considered a core component in dsRNA uptake in some insect species.Investigation related to the potential function of SIL1 in dsRNA uptake can contribute to a further understanding of RNA interference(RNAi)mechanisms in insects and agricultural pest control.However,the role of SIL1 in dsRNA uptake in insects such as aphids remains controversial.We have thoroughly analyzed the role of SIL1 from the model aphid Acyrthosiphon pisum(ApSIL1)in cellular dsRNA to clarify its function.First,the induced expression of ApSIL1 upon dsRNA oral exposure provided a vital clue for the possible involvement of ApSIL1 in cellular dsRNA uptake.Subsequent in vivo experiments using the RNAi-of-RNAi approach for ApSIL1 supported our hypothesis that the silencing efficiencies of reporter genes were reduced after inhibition of ApSIL1 expression.The impaired biological phenotypes of aphids,including cumulative average offspring,deformities of the nymph,and mortality upon pathogen infection,were then observed in the treatment group.Thereafter,in vitro dual-luciferase reporter assay showed compelling evidence that the luciferin signal was significantly attenuated when dsluciferase or dsGFP was transferred into ApSIL1-transfected Drosophila S2 cells.These observations further confirmed that the signal of Cy3-labeled dsRNA was rapidly attenuated with time in ApSIL1-transfected Drosophila S2 cells.Overall,these findings conclusively establish that ApSIL1 is involved in dsRNA uptake in A.pisum.展开更多
Aphids are important agricultural pests,vectors of many plant viruses and have sophisticated relationships with symbiotic microorganisms.Abundant asymptomatic RNA viruses have been reported in aphids due to the applic...Aphids are important agricultural pests,vectors of many plant viruses and have sophisticated relationships with symbiotic microorganisms.Abundant asymptomatic RNA viruses have been reported in aphids due to the application of RNA-seq,but aphid-virus interactions remain unclear.Bunyavirales is the most abundant RNA virus order,which can infect mammals,arthropods,and plants.However,many bunyaviruses have specific hosts,such as insects.Here,we discovered 18 viruses from 10 aphid species by RNA-seq.Importantly,a widespread presence bunyavirus,Aphid bunyavirus 1(ABV-1),was determined to have a wide host range,infecting and replicating in all 10 tested aphid species.ABV-1 may be transmitted horizontally during feeding on plant leaves and vertically through reproduction.In a comparison of the physiological parameters of ABV-1high and ABV-1low strains of pea aphid,higher ABV-1 titers reduced the total nymphal duration and induced the reproduction.Moreover,viral titer significantly affected the lipid and protein contents in pea aphids.In summary,we proposed that ABV-1 may have stable symbiont-like relationships with aphids,and these observations may provide a new direction for studying bunyaviruses in aphids and establishing a model for virus-aphid interactions.展开更多
基金the Natural Science Foundation of China(Grant Numbers 72074014 and 72004012).
文摘Purpose:Many science,technology and innovation(STI)resources are attached with several different labels.To assign automatically the resulting labels to an interested instance,many approaches with good performance on the benchmark datasets have been proposed for multi-label classification task in the literature.Furthermore,several open-source tools implementing these approaches have also been developed.However,the characteristics of real-world multi-label patent and publication datasets are not completely in line with those of benchmark ones.Therefore,the main purpose of this paper is to evaluate comprehensively seven multi-label classification methods on real-world datasets.Research limitations:Three real-world datasets differ in the following aspects:statement,data quality,and purposes.Additionally,open-source tools designed for multi-label classification also have intrinsic differences in their approaches for data processing and feature selection,which in turn impacts the performance of a multi-label classification approach.In the near future,we will enhance experimental precision and reinforce the validity of conclusions by employing more rigorous control over variables through introducing expanded parameter settings.Practical implications:The observed Macro F1 and Micro F1 scores on real-world datasets typically fall short of those achieved on benchmark datasets,underscoring the complexity of real-world multi-label classification tasks.Approaches leveraging deep learning techniques offer promising solutions by accommodating the hierarchical relationships and interdependencies among labels.With ongoing enhancements in deep learning algorithms and large-scale models,it is expected that the efficacy of multi-label classification tasks will be significantly improved,reaching a level of practical utility in the foreseeable future.Originality/value:(1)Seven multi-label classification methods are comprehensively compared on three real-world datasets.(2)The TextCNN and TextRCNN models perform better on small-scale datasets with more complex hierarchical structure of labels and more balanced document-label distribution.(3)The MLkNN method works better on the larger-scale dataset with more unbalanced document-label distribution.
基金supported by grants from the Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs(Grant Nos.18ZX09201-015 and 2017ZX09304015)the Innovation Fund for Medical Sciences of the Chinese Academy of Medical Sciences(Grant No.CIFMS,2016-I2M-1-001)。
文摘Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.
基金the Major State Basic Research Development Program of China, No. 2009CB522902the National Natural Science Foundation of China, No. 30760320+1 种基金the Jiangxi Key R&D Projectthe Natural Science Foundation of Jiangxi Province, No. 2010Gzy0126
文摘The treatment duration of heat-sensitive moxibustion（approximately 40 minutes on average） is longer than that of traditional suspended moxibustion.The present study investigated expression changes of three inflammatory and apoptosis-associated proteins（inducible nitric oxide synthase,cyclooxygenase-2 and caspase-3） in transient middle cerebral artery occlusion model rats following suspended moxibustion for 40 minutes,to explore the mechanisms underlying neuroprotective action of suspended moxibustion.The results indicated that suspended moxibustion at acupoint Dazhui（DU 14） for 40 minutes reduced the cortical expression of caspase-3,cyclooxygenase-2 and inducible nitric oxide synthase proteins of transient middle cerebral artery occlusion model rats,as well as decreasing infarct volume and ameliorating the neurological deficit score.Outcomes with 40 minutes of moxibustion were superior to the outcomes after suspended moxibustion for 15 minutes.
基金supported by National Natural Science Foundation of China(Grant No.11775257)。
文摘During ion cyclotron resonance heating,the sheath power dissipation caused by ion acceleration in the radio frequency(RF)sheath is one of the main causes of RF power loss in the tokamak edge region.To estimate the power dissipation of an RF sheath in the ion cyclotron range of frequency(ICRF),a 1 D fluid model for the multi-component plasma sheath driven by a sinusoidal disturbance current in the ICRF is presented.By investigation of the sheath potential and ion flux at the wall,it is shown that the larger frequency and lower amplitude of the disturbance current can cause smaller sheath power dissipation.The effect of the energetic ion on the sheath power dissipation depends on the disturbance current.For large amplitude of disturbance current,the increase in the concentration and energy of the energetic ion leads to a decrease in sheath power dissipation.While for a small disturbance current,the sheath power dissipation demonstrates non-monotonic variation with the concentration and energy of the energetic ion.In addition,the sheath power dissipation is found to have a small increase in the presence of light impurity ions with low valence.
基金This research was supported by the National Natural Science Foundation of China(32072423).
文摘Sap-sucking insects often transmit plant viruses but also carry insect viruses,which infect insects but not plants.The impact of such insect viruses on insect host biology and ecology is largely unknown.Here,we identified a novel insect-specific virus carried by brown citrus aphid(Aphis citricidus),which we tentatively named Aphis citricidus picornavirus(AcPV).Phylogenetic analysis discovered a monophyletic cluster with AcPV and other unassigned viruses,suggesting that these viruses represent a new family in order Picornavirales.Systemic infection with AcPV triggered aphid antiviral immunity mediated by RNA interference,resulting in asymptomatic tolerance.Importantly,we found that AcPV was transmitted horizontally by secretion of the salivary gland into the feeding sites of plants.AcPV influenced aphid stylet behavior during feeding and increased the time required for intercellular penetration,thus promoting its transmission among aphids with plants as an intermediate site.The gene expression results suggested that this mechanism was linked with transcription of salivary protein genes and plant defense hormone signaling.Together,our results show that the horizontal transmission of AcPV in brown citrus aphids evolved in a manner similar to that of the circulative transmission of plant viruses by insect vectors,thus providing a new ecological perspective on the activity of insect-specific viruses found in aphids and improving the understanding of insect virus ecology.
基金supported by U. S. National Institute of Health Grants R01 HL124122, AR067766American Heart Association Grant 12SDG12070174supported by the National Natural Science Foundation of China (Grant No. 81401155)
文摘Multidrug resistance(MDR) remains a major clinical obstacle to successful cancer treatment.Although diverse mechanisms of MDR have been well elucidated, such as dysregulation of drugs transporters, defects of apoptosis and autophagy machinery, alterations of drug metabolism and drug targets, disrupti on of redox homeostasis, the exact mechanisms of MDR in a specific cancer patient and the cross-talk among these different mechanisms and how they are regulated are poorly understood.Micro RNAs(mi RNAs) are a new class of small noncoding RNAs that could control the global activity of the cell by post-transcriptionally regulating a large variety of target genes and proteins expression.Accumulating evidence shows that mi RNAs play a key regulatory role in MDR through modulating various drug resistant mechanisms mentioned above, thereby holding much promise for developing novel and more effective individualized therapies for cancer treatment. This review summarizes the various MDR mechanisms and mainly focuses on the role of mi RNAs in regulating MDR in cancer treatment.
基金This study was supported by the Guangdong Natural Science Foundation(No.2017A030310192)the Fundamental Research Funds for the Central Universities(17ykpy84)We thank Springer Nature for professional editing.
文摘Background:Identification of activated epidermal growth factor receptor(EGFR)mutations and application of EGFR-tyrosine kinase inhibitors(EGFR-TKIs)have greatly changed the therapeutic strategies of non-small-cell lung cancer(NSCLC).However,the long-term efficacy of EGFR-TKI therapy is limited due to the development of drug resistance.The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR-TKIs in advanced NSCLC patients with activated EGFR mutations.Methods:We retrospectively reviewed the clinical data from 416 patients with stage III/IV or recurrent NSCLC who received an initial EGFR-TKI treatment,from April 2004 and March 2011,at the Sun Yat-sen University Cancer Center.Several genetic alterations associated with the efficacy of EGFR-TKIs,including the alterations in BIM,ALK,KRAS,PIK3CA,PTEN,MET,IGF1R,and ROS1,were detected by the routine clinical technologies.The progression-free survival(PFS)and overall survival(OS)were compared between different groups using Kaplan-Meier survival analysis with the log-rank test.A Cox regression model was used to estimate multivariable-adjusted hazard ratios(HRs)and their 95%confi-dence intervals(95%CIs)associated with the PFS and OS.Results:Among the investigated patients,169 NSCLC patients harbored EGFR-sensitive mutations.EGFR-mutant patients having PTEN deletion had a shorter PFS and OS than those with intact PTEN(P=0.003 for PFS,and P=0.034 for OS).In the combined molecular analysis of EGFR signaling pathway and resistance genes,we found that EGFR-mutant patients coexisted with aberrant alterations in EGFR signaling pathway and those having resistant genes had a statistically poorer PFS than those without such alterations(P<0.001).A Cox proportional regression model determined that PTEN deletion(HR=4.29,95%CI=1.72-10.70)and low PTEN expression(HR=1.96,95%CI=1.22-3.13),MET FISH+(HR=2.83,95%CI=1.37-5.86)were independent predictors for PFS in patients with EGFR-TKI treatment after adjustment for multiple factor.Conclusions:We determined that the coexistence of genetic alterations in cancer genes may explain primary resistance to EGFR-TKIs.
基金This study was supported by the Natural Science Foundation of Guangdong Province(2020A1515010105)Joint Fund of the National Natural Science Foundation of China and Natural Science Foundation of Guangdong Province(U1601224).
文摘Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
基金supported by the School-level Natural Key Research Projects of West Anhui University(Grant No.WXZR201710)
文摘With the aid of the bosonic mode conversions in two different coordinate frames, we show that （1） the coordinate eigenstate is exactly the EPR entangled state representation, and （2） the Laguerre-Ganssian （LG） mode is exactly the wave function of the common eigenvector of the orbital angular momentum and the total photon number operator. Moreover, by using the conversion of the bosonic modes, the Wigner representation of the LG mode can be obtained directly. It provides an alternative to the method of Simon and Agarwal.
基金supported by the National Natural Science Foundation of China(32102195)the National Natural Science Foundation of China-Major International(Regional)Joint Research Project(32020103010)the 111 Project(B18044).
文摘Systemic RNA interference deficient-1-like(SIL1)is considered a core component in dsRNA uptake in some insect species.Investigation related to the potential function of SIL1 in dsRNA uptake can contribute to a further understanding of RNA interference(RNAi)mechanisms in insects and agricultural pest control.However,the role of SIL1 in dsRNA uptake in insects such as aphids remains controversial.We have thoroughly analyzed the role of SIL1 from the model aphid Acyrthosiphon pisum(ApSIL1)in cellular dsRNA to clarify its function.First,the induced expression of ApSIL1 upon dsRNA oral exposure provided a vital clue for the possible involvement of ApSIL1 in cellular dsRNA uptake.Subsequent in vivo experiments using the RNAi-of-RNAi approach for ApSIL1 supported our hypothesis that the silencing efficiencies of reporter genes were reduced after inhibition of ApSIL1 expression.The impaired biological phenotypes of aphids,including cumulative average offspring,deformities of the nymph,and mortality upon pathogen infection,were then observed in the treatment group.Thereafter,in vitro dual-luciferase reporter assay showed compelling evidence that the luciferin signal was significantly attenuated when dsluciferase or dsGFP was transferred into ApSIL1-transfected Drosophila S2 cells.These observations further confirmed that the signal of Cy3-labeled dsRNA was rapidly attenuated with time in ApSIL1-transfected Drosophila S2 cells.Overall,these findings conclusively establish that ApSIL1 is involved in dsRNA uptake in A.pisum.
基金This research was supported by National Natural Sci-ence Foundation(32072423)National Natural Science Foundation of China-Major International(Regional)Joint Research Project(32020103010)+1 种基金111 Project(B18044)the Foundation Project of Southwest University(SWU019033).We thank Dr Bi-Yue Ding(Academy of Agricultural Sciences.Southwest Univer-sity)for the technical assistance in western bloting.The Ap-Uny colony and Ap-Efr colony were kindly pro-vided by Professors Tong-Xian Liu and Giuy Smagghe,respectively.
文摘Aphids are important agricultural pests,vectors of many plant viruses and have sophisticated relationships with symbiotic microorganisms.Abundant asymptomatic RNA viruses have been reported in aphids due to the application of RNA-seq,but aphid-virus interactions remain unclear.Bunyavirales is the most abundant RNA virus order,which can infect mammals,arthropods,and plants.However,many bunyaviruses have specific hosts,such as insects.Here,we discovered 18 viruses from 10 aphid species by RNA-seq.Importantly,a widespread presence bunyavirus,Aphid bunyavirus 1(ABV-1),was determined to have a wide host range,infecting and replicating in all 10 tested aphid species.ABV-1 may be transmitted horizontally during feeding on plant leaves and vertically through reproduction.In a comparison of the physiological parameters of ABV-1high and ABV-1low strains of pea aphid,higher ABV-1 titers reduced the total nymphal duration and induced the reproduction.Moreover,viral titer significantly affected the lipid and protein contents in pea aphids.In summary,we proposed that ABV-1 may have stable symbiont-like relationships with aphids,and these observations may provide a new direction for studying bunyaviruses in aphids and establishing a model for virus-aphid interactions.
