Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resi...Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.展开更多
背景与目的分析胸外科术后重症患者住重症加强护理病房(intensive care unit, ICU)期间的下肢深静脉血栓(deep venous thrombosis, DVT)发生率与凝血指标。方法回顾性分析2016年7月-2018年6月接受物理预防血栓的胸外科术后重症患者,将...背景与目的分析胸外科术后重症患者住重症加强护理病房(intensive care unit, ICU)期间的下肢深静脉血栓(deep venous thrombosis, DVT)发生率与凝血指标。方法回顾性分析2016年7月-2018年6月接受物理预防血栓的胸外科术后重症患者,将床旁下肢静脉超声、血常规、凝血四项、血栓弹力图等结果完善的病例纳入研究,对发生血栓人群的一般信息、病种、手术方式、凝血指标等进行分析。结果共纳入患者50例,年龄22岁-80岁,男34例,女16例。共有11例患者出现小腿深静脉血栓(22.0%),男性发生术后血栓的比例为29.4%(10/34),女性为6.3%(1/16)。恶性肿瘤的DVT发生率为23.5%(8/34),非恶性肿瘤的发生率为18.6%(3/16)。比较发生血栓和未发生血栓组的血小板计数、凝血四项、血栓弹力图等,除活化部分凝血活酶时间血栓组较无血栓组显著延长外,余无统计学差异。结论即便在充分物理预防的基础上,胸科术后重症患者下肢深静脉血栓仍为高发,且男性、恶性肿瘤患者多见;术后超声筛查有助于早期发现DVT。展开更多
A new orbit of Triton was provided by our previous work, benefitted by new Gaia Data, both in a new precise reduction of charge-coupled device observations and in the planetary ephemeris INPOP19 a.In this paper, we pr...A new orbit of Triton was provided by our previous work, benefitted by new Gaia Data, both in a new precise reduction of charge-coupled device observations and in the planetary ephemeris INPOP19 a.In this paper, we provide a new ephemeris for another main Neptunian satellite, Nereid. The orbit is fitted for the newest observations, including 2 075 ground-based observations during the period 1949-2018 and 83 space observations acquired by the Voyager 2 spacecraft in 1989. The dynamical model used here is consistent with that of our previous work. For the ground-based absolute observations of Nereid, the rootmean-square deviations are 0.201′′in right ascension and 0.189′′in declination. Finally, a comparison with the HORIZONS ephemeris is made and discussed.展开更多
With unique orbital and physical characteristics,Triton is a very important target because it may contain information of the origin and evolution of the solar system.Besides space explorations,ground-based observation...With unique orbital and physical characteristics,Triton is a very important target because it may contain information of the origin and evolution of the solar system.Besides space explorations,ground-based observations over long time also play a key role on research of Triton.High-precision positions of Triton obtained from ground telescopes are of great significance for studying its orbital evolution and the physical properties of Neptune.As a long-term observational target,Triton has been observed by the 1.56 m telescope of Shanghai Astronomical Observatory since 1996.In this paper,based on our AAPPDI software and with Gaia DR2 as the reference catalog,604 positions of Triton during 2010–2014 are calculated,with standard errors of 19–88 mas.A comparison between our results and the ephemeris(DE431+nep096)is also given.展开更多
Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A...Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A Thousand Gold in C.E.652.The tablet is used to treat diabetes in China owing to its powerful hypoglycemic properties.However,little is known about the metabolic mechanisms underlying these properties.Methods:Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry-based metabolomics approach was performed to explore the metabolic mechanism of JQJT in the treatment of type 2 diabetes mellitus(T2DM).Results:The metabolomic pathway analysis and the Kyoto Encyclopedia of Genes and Genomes database were used to screen out 25 potential biomarkers and construct pertinent metabolic pathways.Five metabolites,such as allantoic acid and taurine,were downregulated and 20 metabolites were upregulated in the urine of T2DM rats.The biomarkers in the JQJT group exhibited a good callback trend.It is speculated that JQJT can alleviate T2DM by regulating the disorders of taurine,hypotaurine,phenylalanine,ascorbate,and aldarate metabolism,as well as pentose and glucuronate interconversions.Conclusion:This study will be meaningful in the clinical application of JQJT and will be valuable for further exploration of the metabolic mechanisms underlying its properties.展开更多
A total of 25 strains were isolated from the intestinal tract of Mystus macropterus. The inhibitory effects of extracellular enzyme activity to common aquat- ic pathogenic bacteria were screened. A probiotic DQHY -7 s...A total of 25 strains were isolated from the intestinal tract of Mystus macropterus. The inhibitory effects of extracellular enzyme activity to common aquat- ic pathogenic bacteria were screened. A probiotic DQHY -7 strain was isolated, and its safety was detected. DQHY -7 strain was preliminarily identified by mor- phological observation, and physiological and biochemical test. Research results showed that DQHY -7 strain had relatively strong production capacities of amylase, cellulase and protease, and could restrict the growth of Escherichia coli, Aeromonas hydrophila and Pseudomonas fluorescens. Results of acute toxicity test showed that 1. 0 × 108 CFU/mL DQHY -7 bacterial suspension showed no pathogenicity to M. macropterus. According to the colony growth pattern and physiological-bio- chemical characteristics of DQHY -7, the strain was identified to be Bacillus subtilis. Research results showed that DQHY -7 strain could be used as a new candi- date strain for feeding microecologicalagent.展开更多
Background:As type 2 diabetes mellitus(T2DM)biomarkers,branched-chain amino acids(BCAAs:valine,leucine and isoleucine)and aromatic amino acids(AAAs:phenylalanine,tryptophan and tyrosine)may be correlated with the occu...Background:As type 2 diabetes mellitus(T2DM)biomarkers,branched-chain amino acids(BCAAs:valine,leucine and isoleucine)and aromatic amino acids(AAAs:phenylalanine,tryptophan and tyrosine)may be correlated with the occurrence and development of T2DM.However,there is still no consensus on the disperse and isolated biomarkers of T2DM.Purpose:To explore the correlation between amino acids and T2DM based on integrated biomarker approach revealed.Methods:PubMed,Web of Science and CNKI were selected to search the literature published until August 31,2019.The included studies described the association between BCAAs,AAAs and T2DM.Random effect model and fixed effect model were adopted in pooled analysis to determine mean difference and 95 percent confidence interval of metabolites.Integrated biomarker was constructed in form of concentration change ratios or risk ratio(RR),relative risk(HR)and odds ratio(OR)of BCAAs and AAAs to reflect the integrated change information of amino acids.Results:The selected 20 studies contained 14942 healthy individuals and 3615 T2DM patients.The levels of BCAAs,phenylalanine and tyrosine both in plasma and serum samples were increased among all T2DM patients compared with those of the healthy control subjects(P<0.00001).However,the mean difference of tryptophan concentration was not statistically significant(P=0.60).The concentration change ratios or HR/RR/OR of BCAAs and AAAs were connected to form integrated biomarker.Conclusion:The integrated biomarker including BCAAs and AAAs could reflect the basic characteristics of T2DM,which has the potential clinical value on comprehensive diagnosis of T2DM.展开更多
Insulin resistance(IR)is a significant feature and one of the basic links in the pathogenesis of type 2 diabetes mellitus(T2DM).Chinese material medica(CMM)has promoted the development of traditional Chinese medicine ...Insulin resistance(IR)is a significant feature and one of the basic links in the pathogenesis of type 2 diabetes mellitus(T2DM).Chinese material medica(CMM)has promoted the development of traditional Chinese medicine due to its definite clinical efficacy in the treatment of IR and T2DM.However,owing to the fact that the mechanism of CMM is characterized by“multiple components and multiple targets”,which has not been effectively interpreted,result in the scientificity of clinical efficacy with CMM is controversial.Therefore,this article summarized the mechanisms of CMM and its main active components in improving IR and preventing and treating T2DM,whose aim is to provide valuable reference for the research mechanism on the treatment of IR and T2DM.展开更多
基金supported by the National Key R&D Program of China(Grant No.2022YFC3401404)the National Natural Science Foundation of China(Grant Nos.32170935 and 31930066).
文摘Cancer immunotherapy,a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity,is currently an important clinical strategy for cancer treatment;however,tumors can develop drug resistance to immune surveillance,resulting in poor response rates and low therapeutic efficacy.In addition,changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents.Furthermore,tumors create an immunosuppressive microenvironment via immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction.To address these challenges,smart drug delivery systems(SDDSs)have been developed to overcome tumor cell resistance to immunomodulators,restore or boost immune cell activity,and magnify immune responses.To combat resistance to small molecules and monoclonal antibodies,SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells,thus increasing the drug concentration at the target site and improving efficacy.Herein,we discuss how SDDSs overcome drug resistance during cancer immunotherapy,with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment.SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented.Finally,we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy.We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.
文摘背景与目的分析胸外科术后重症患者住重症加强护理病房(intensive care unit, ICU)期间的下肢深静脉血栓(deep venous thrombosis, DVT)发生率与凝血指标。方法回顾性分析2016年7月-2018年6月接受物理预防血栓的胸外科术后重症患者,将床旁下肢静脉超声、血常规、凝血四项、血栓弹力图等结果完善的病例纳入研究,对发生血栓人群的一般信息、病种、手术方式、凝血指标等进行分析。结果共纳入患者50例,年龄22岁-80岁,男34例,女16例。共有11例患者出现小腿深静脉血栓(22.0%),男性发生术后血栓的比例为29.4%(10/34),女性为6.3%(1/16)。恶性肿瘤的DVT发生率为23.5%(8/34),非恶性肿瘤的发生率为18.6%(3/16)。比较发生血栓和未发生血栓组的血小板计数、凝血四项、血栓弹力图等,除活化部分凝血活酶时间血栓组较无血栓组显著延长外,余无统计学差异。结论即便在充分物理预防的基础上,胸科术后重症患者下肢深静脉血栓仍为高发,且男性、恶性肿瘤患者多见;术后超声筛查有助于早期发现DVT。
基金The National Natural Science Foundation of China (grant number 81773891)the National Great New Drugs Development Project of China (grant number 2017ZX09301-040)+1 种基金the Beijing Municipal Science and Technology Commission (grant number XMLX201704, 2018-2-2242, 7194280)the Open Research Fund of the State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicinal Resources.
基金funded by the B-type Strategic Priority Program of the Chinese Academy of Sciences(Grant No.XDB41000000)the National Natural Science Foundation of China(NSFC)under Nos.12073062 and 11803019the Preresearch Project on Civil Aerospace Technologies funded by the China National Space Administration(Grant No.D020303)。
文摘A new orbit of Triton was provided by our previous work, benefitted by new Gaia Data, both in a new precise reduction of charge-coupled device observations and in the planetary ephemeris INPOP19 a.In this paper, we provide a new ephemeris for another main Neptunian satellite, Nereid. The orbit is fitted for the newest observations, including 2 075 ground-based observations during the period 1949-2018 and 83 space observations acquired by the Voyager 2 spacecraft in 1989. The dynamical model used here is consistent with that of our previous work. For the ground-based absolute observations of Nereid, the rootmean-square deviations are 0.201′′in right ascension and 0.189′′in declination. Finally, a comparison with the HORIZONS ephemeris is made and discussed.
基金the financial support of the National Natural Science Foundation of China(Grant Nos.11803019,12073062 and 11703007)the Hubei Provincial Department of Education(Grant No.B2020162)。
文摘With unique orbital and physical characteristics,Triton is a very important target because it may contain information of the origin and evolution of the solar system.Besides space explorations,ground-based observations over long time also play a key role on research of Triton.High-precision positions of Triton obtained from ground telescopes are of great significance for studying its orbital evolution and the physical properties of Neptune.As a long-term observational target,Triton has been observed by the 1.56 m telescope of Shanghai Astronomical Observatory since 1996.In this paper,based on our AAPPDI software and with Gaia DR2 as the reference catalog,604 positions of Triton during 2010–2014 are calculated,with standard errors of 19–88 mas.A comparison between our results and the ephemeris(DE431+nep096)is also given.
基金supported by the National Key Research and Development Program of China(No.2020YFF01014606)the National Natural Science Foundation of China(No.82073741).
文摘Background:Si-Miao Sun wrote about the Jinqi Jiangtang tablet(JQJT)that is derived from the traditional Chinese herbal medicine Huanglian(Coptis Chinensis Franch)pills in the Essential Recipes for Emergent Use Worth A Thousand Gold in C.E.652.The tablet is used to treat diabetes in China owing to its powerful hypoglycemic properties.However,little is known about the metabolic mechanisms underlying these properties.Methods:Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry-based metabolomics approach was performed to explore the metabolic mechanism of JQJT in the treatment of type 2 diabetes mellitus(T2DM).Results:The metabolomic pathway analysis and the Kyoto Encyclopedia of Genes and Genomes database were used to screen out 25 potential biomarkers and construct pertinent metabolic pathways.Five metabolites,such as allantoic acid and taurine,were downregulated and 20 metabolites were upregulated in the urine of T2DM rats.The biomarkers in the JQJT group exhibited a good callback trend.It is speculated that JQJT can alleviate T2DM by regulating the disorders of taurine,hypotaurine,phenylalanine,ascorbate,and aldarate metabolism,as well as pentose and glucuronate interconversions.Conclusion:This study will be meaningful in the clinical application of JQJT and will be valuable for further exploration of the metabolic mechanisms underlying its properties.
基金Supported by the Planning Project of Basic Scientific Research Funds of Chongqing(2012-esfc-jbky-00405)
文摘A total of 25 strains were isolated from the intestinal tract of Mystus macropterus. The inhibitory effects of extracellular enzyme activity to common aquat- ic pathogenic bacteria were screened. A probiotic DQHY -7 strain was isolated, and its safety was detected. DQHY -7 strain was preliminarily identified by mor- phological observation, and physiological and biochemical test. Research results showed that DQHY -7 strain had relatively strong production capacities of amylase, cellulase and protease, and could restrict the growth of Escherichia coli, Aeromonas hydrophila and Pseudomonas fluorescens. Results of acute toxicity test showed that 1. 0 × 108 CFU/mL DQHY -7 bacterial suspension showed no pathogenicity to M. macropterus. According to the colony growth pattern and physiological-bio- chemical characteristics of DQHY -7, the strain was identified to be Bacillus subtilis. Research results showed that DQHY -7 strain could be used as a new candi- date strain for feeding microecologicalagent.
基金supported by the National Natural Science Foundation of China(grant number 81773891)the National Great New Drugs Development Project of China(grant number 2017ZX09301-040)the Beijing Municipal Science and Technology Commission(grant number XMLX201704,2018-2-2242,7194280).
文摘Background:As type 2 diabetes mellitus(T2DM)biomarkers,branched-chain amino acids(BCAAs:valine,leucine and isoleucine)and aromatic amino acids(AAAs:phenylalanine,tryptophan and tyrosine)may be correlated with the occurrence and development of T2DM.However,there is still no consensus on the disperse and isolated biomarkers of T2DM.Purpose:To explore the correlation between amino acids and T2DM based on integrated biomarker approach revealed.Methods:PubMed,Web of Science and CNKI were selected to search the literature published until August 31,2019.The included studies described the association between BCAAs,AAAs and T2DM.Random effect model and fixed effect model were adopted in pooled analysis to determine mean difference and 95 percent confidence interval of metabolites.Integrated biomarker was constructed in form of concentration change ratios or risk ratio(RR),relative risk(HR)and odds ratio(OR)of BCAAs and AAAs to reflect the integrated change information of amino acids.Results:The selected 20 studies contained 14942 healthy individuals and 3615 T2DM patients.The levels of BCAAs,phenylalanine and tyrosine both in plasma and serum samples were increased among all T2DM patients compared with those of the healthy control subjects(P<0.00001).However,the mean difference of tryptophan concentration was not statistically significant(P=0.60).The concentration change ratios or HR/RR/OR of BCAAs and AAAs were connected to form integrated biomarker.Conclusion:The integrated biomarker including BCAAs and AAAs could reflect the basic characteristics of T2DM,which has the potential clinical value on comprehensive diagnosis of T2DM.
基金the National Natural Science Foundation of China(81773891)the National Great New Drugs Development Project of China(2017ZX09301-040)+3 种基金the Beijing Natural Science Foundation(7162092)Beijing Talents Project(2017A19)Beijing Municipal Science&Technology Commission(XMLX201704,Z161100000516074)the Open Research Fund of the State Key Laboratory Breeding Base of Systematic Research,Development and Utilization of Chinese Medicinal Resources.
文摘Insulin resistance(IR)is a significant feature and one of the basic links in the pathogenesis of type 2 diabetes mellitus(T2DM).Chinese material medica(CMM)has promoted the development of traditional Chinese medicine due to its definite clinical efficacy in the treatment of IR and T2DM.However,owing to the fact that the mechanism of CMM is characterized by“multiple components and multiple targets”,which has not been effectively interpreted,result in the scientificity of clinical efficacy with CMM is controversial.Therefore,this article summarized the mechanisms of CMM and its main active components in improving IR and preventing and treating T2DM,whose aim is to provide valuable reference for the research mechanism on the treatment of IR and T2DM.
