The solid rocket motors for the escape system of China’s LM-2 F manned launch vehicle are described,the key technologies and technical innovations utilized are summarized.The technical features and development of for...The solid rocket motors for the escape system of China’s LM-2 F manned launch vehicle are described,the key technologies and technical innovations utilized are summarized.The technical features and development of foreign manned launch abort systems are also presented.The development trends of the solid rocket motor for future Chinese manned launch vehicle escape systems are proposed,which can provide a reference for the future development of manned launch vehicle escape systems.展开更多
The asymmetric effects on the escape rates from the stable states x±in the bistable system are analyzed. The results indicate that the multiplicative noise and the additive noise always enhance the particle escap...The asymmetric effects on the escape rates from the stable states x±in the bistable system are analyzed. The results indicate that the multiplicative noise and the additive noise always enhance the particle escape from stable states x±of bistable.However,the asymmetric parameter r enhances the particle escape from stable state x_+,and holds back the particle escape from stable state x_-.展开更多
Antisense oligodeoxynucleotide(ASODN)can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing,in turn,plays antitumor therapeutic roles.In the s...Antisense oligodeoxynucleotide(ASODN)can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing,in turn,plays antitumor therapeutic roles.In the study,a novel HIF-1αASODN-loaded nanocomposite was formulated to efficiently deliver gene to the target RNA.The physicochemical properties of nanocomposite were characterized using TEM,FTIR,DLS and zeta potentials.The mean diameter of resulting GEL-DGL-FA-ASODN-DCA nanocomposite was about 170–192 nm,and according to the agarose gel retardation assay,the loading amount of ASODN accounted for 166.7 mg/g.The results of cellular uptake showed that the nanocomposite could specifically target to HepG2 and Hela cells.The cytotoxicity assay demonstrated that the toxicity of vectors was greatly reduced by using DCA to reversibly block the cationic DGL.The subcellular distribution images clearly displayed the lysosomal escape ability of the DCA-modified nanocomposite.In vitro exploration of molecular mechanism indicated that the nanocomposite could inhibit m RNA expression and HIF-1αprotein translation at different levels.In vivo optical images and quantitative assay testified that the formulation accumulated preferentially in the tumor tissue.In vivo antitumor efficacy research confirmed that this nanocomposite had significant antitumor activity and the tumor inhibitory rate was 77.99%.These results manifested that the GEL-DGL-FA-ASODNDCA nanocomposite was promising in gene therapeutics for antitumor by interacting directly with target RNA.展开更多
The relative escape rate (RER) in the bistable sawtooth system driven by correlated white noises was studied in the case of linear multiplicative noise coefficient.And we compare the RER of linear multiplicative noise...The relative escape rate (RER) in the bistable sawtooth system driven by correlated white noises was studied in the case of linear multiplicative noise coefficient.And we compare the RER of linear multiplicative noise coefficient with the RER of the piecewise constant multiplicative noise coefficient in the bistable sawtooth system,finally compare the RER of the bistable sawtooth potential with the RER of the quartic potential in the case of linear multiplicative noise coefficient.It can be seen that the form of the multiplicative noise coefficient and the nonlinearity of potential have an important influence on the resonant activation and the suppression of the RER.The resonant activation of the RER vanishes in the negative correlation when the multiplicative noise coefficient was shifted from piecewise constant to linear function in the bistable sawtooth potential.The suppression of the RER disappears in the negative correlation when thelinear potential is converted into nonlinear one.展开更多
A three-state Markovian noise is investigated.Its probability density and statistical properties are obtained. Escape of particles for a system with potential barrier only driven by this noise is investigated.It is sh...A three-state Markovian noise is investigated.Its probability density and statistical properties are obtained. Escape of particles for a system with potential barrier only driven by this noise is investigated.It is shown that,in some circumstances,this noise can make the particles escape over the potential barrier;but in other circumstances,it cannot. Resonant activation phenomenon appears for the system considered by us.展开更多
Despite the support of all kinds of fire prevention measures and high-tech fire prevention equipment,fires still occur frequently because of both anthro-pogenic factors and natural disasters.This issue has drawn the a...Despite the support of all kinds of fire prevention measures and high-tech fire prevention equipment,fires still occur frequently because of both anthro-pogenic factors and natural disasters.This issue has drawn the attention of schools,all levels of government,and other organizations.Many types of organi-zations carry out fire drills throughout the year.Because this kind of drill cannot anticipate the specific circumstances of each fire,which are generally far more complicated than drills,most people cannot correctly choose the optimal escape route from real fires.Thus,a fire-scene virtual simulation system based on the Dijkstra algorithm is here proposed to address such problems as casualties caused by frequent fires and the inability of most people to correctly choose a fire escape route.This virtual fire escape simulation system uses Maya to carry out 3D recon-struction of the fire scene,the Unity engine to conduct interactive function design,and the Dijkstra algorithm to calculate the best escape route.The results of the example indicate that the simulation system solves the problems of the traditional simulation system,such as stiffness,lack of intelligence,and poor simulation.展开更多
Prey species may have their own optimal escape strategy to balance predation risks and the energetic cost of fleeing.Some species have an advantage when maintaining a short fleeing distance,while others may favour an ...Prey species may have their own optimal escape strategy to balance predation risks and the energetic cost of fleeing.Some species have an advantage when maintaining a short fleeing distance,while others may favour an earlier escape based on microhabitat,size,or body condition.Here,we examined the escape behaviour of the three syntopic Northeast Asian anuran species:Mongolian toads(Strauchbufo raddei),Amur brown frogs(Rana amurensis),and Japanese treefrogs(Dryophytes japonicus)in Mongolia,Russia,China and DPR Korea.We examined flight initiation distance(FID;the distance from a potential predator to the point when the individual starts to flee)and distance fled(DF;distance between flight initiation and flight termination points)of each species and the effects of microhabitat,sex,and body size.Strauchbufo raddei and R.amurensis had a longer FID than D.japonicus,and S.raddei also had a longer DF than D.japonicus.These trends remained similar when dividing FID and DF by a size proxy(snout-vent length)for all individuals.This suggests that the treefrog D.japonicus used a strategy to stay immobile even when they were detected,and the toad S.raddei reacted quicker and more sensitively to predators despite the presence of toxin.Female S.raddei had a significantly longer FID than males suggesting that females are more sensitive to predation risk in this species,but body size was not significant for any of the three species.Our results indicate that the three sympatric species have different escaping strategies,likely related to differences in physiology and crypticity.展开更多
In the original publication of the article,the affiliation“College of Earth and Planetary Sciences,University of Chinese Academy of Sciences,Beijing,People’s Republic of China”for author Ziqi Wang was missing and i...In the original publication of the article,the affiliation“College of Earth and Planetary Sciences,University of Chinese Academy of Sciences,Beijing,People’s Republic of China”for author Ziqi Wang was missing and included in this correction article.展开更多
Objective: To investigate the expression of Fas, Fas ligand (FasL) and CD80 on the cell surface of mouse acute myelomonocytic leukemia cell line WEHI-3 and the function of FasL. Methods: The expression of Fas, Fas...Objective: To investigate the expression of Fas, Fas ligand (FasL) and CD80 on the cell surface of mouse acute myelomonocytic leukemia cell line WEHI-3 and the function of FasL. Methods: The expression of Fas, FasL and CD80 was detected on WEHI-3 cell surface by flow cytometry. Simultaneously the function of FasL was determined by Thymidine (^3H-TdR) Incorporation. Results: The expression of CD80 and Fas on WEHI-3 cell surface was 5.06%±0.41% and 6.75%±2.31% (n=5) respectively, and the expression of FasL was up to 63.73%±5.23% (n=5). The apoptotic rate of YAC-1 cells was 26%±4.5%, 35%±3.2% and 43%±2.7% (n=5) respectively when WEHI-3 (effector cell, E) and Fas^+ YAC-1 cells (target cell, T) were cultured in the ratio of 3:1, 10:1 and 30:1. Conclusion: WEHI-3 cells express high FasL, low Fas and CD80, and can induce apoptosis of Fas^+ YAC-1 cells.展开更多
Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumo...Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.展开更多
A 62-year-old man had chronic hepatitis B virus (HBV) infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient's virologic markers were positive for hepatitis B surface antigen (HBsAg...A 62-year-old man had chronic hepatitis B virus (HBV) infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient's virologic markers were positive for hepatitis B surface antigen (HBsAg), antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc), while antibody to hepatitis B surface antigen (anti-HBs) and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine (LMV) therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin (TB) were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C (HBsAg subtype adw) with immune escape mutations, F8L, $34L, F41S, G44V, F93C, V96G, Lll0I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.展开更多
Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Meth...Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Methods:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL.We identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell subtype.Subsequently,we identified cell markers,including a series of genes associated with immune escape and drug resistance.In addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL samples.Results:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B cells.The drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival promotion.Type III B cells closely communicate with other cells.The key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic value.Conclusion:This study investigated potential immune escape and drug resistance mechanisms in MCL.The results may guide individualized treatment and promote the development of therapeutic drugs.展开更多
Alice Munro is one of the famous Canadian writers and is renowned above all for the astonishing subtlety of her short stories.Her theme has often been the dilemmas of the female coming to terms with family, friends in...Alice Munro is one of the famous Canadian writers and is renowned above all for the astonishing subtlety of her short stories.Her theme has often been the dilemmas of the female coming to terms with family, friends in a small town. This paper attempts to make a brief introduction about the stories of Alice Munro's Runaway and explores the protagonist's choices in the dilemma situation, and then exposes the cruelty of reality is that they cannot get rid of the ineluctable reality of life. Escape is only a temporary action which cannot save them from endless triviality of life. What they should do is not to escape from life, but to adapt to the reality of life.展开更多
AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor escape.METHODS: Streptavidin-biotin-peroxidase immunohistochemis...AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor escape.METHODS: Streptavidin-biotin-peroxidase immunohistochemistry technique was used to study the expression of Fas and FasL protein in 26 gallbladder carcinoma tissues,18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20 chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared with clinicopathological features of gallbladder carcinoma.RESULTS: The positive rates of Fas were not significantly different among carcinoma, adenoma, dysplasia and chronic cholecystitis. The positive rate of FasL in carcinoma was significantly higher than that in chronic cholecystitis (x2 = 4.89, P<0.05). The apoptotic index (AI) in carcinoma was significantly higher than that in adenoma (t'= 4.19, P<0.01) and chronic cholecystitis (t'= 8.06, P<0.01). The AI was significantly lower in well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma than that in poorly-differentiated carcinoma (t'= 2.63, P<0.05) and Nevin Ⅳ-Ⅴ carcinoma(t'= 3.33, P<0.01). The confidence interval (CI) ofinfiltrating lymphocytes in adenoma, chronic cholecystitis, well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma wasvery significantly lower than that in carcinoma (t' = 6.99,P<0.01), adenoma (t' = 3.66, P<0.01), poorly-differentiated carcinoma (t' = 5.31, P<0.01) and Nevin Ⅳ-Ⅴ carcinoma(t' = 3.76, P<0.01), respectively. The CI of apoptosis of infiltrating lymphocytes in well-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma (t = 2.52, P<0.05), and was not significantly lower in Nevin Ⅰ-Ⅲ carcinoma than in Nevin Ⅳ-Ⅴ carcinoma (t = 1.42, P>0.05). Apoptosis of infiltrating lymphocytes was not discovered in adenoma and chronic cholecystitis. CONCLUSION: FasL expressed in gallbladder carcinoma cells permits tumor cells to escape from immune surveillance of organism by inducing apoptosis in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma.展开更多
B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and...B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were con- structed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P〈0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.展开更多
文摘The solid rocket motors for the escape system of China’s LM-2 F manned launch vehicle are described,the key technologies and technical innovations utilized are summarized.The technical features and development of foreign manned launch abort systems are also presented.The development trends of the solid rocket motor for future Chinese manned launch vehicle escape systems are proposed,which can provide a reference for the future development of manned launch vehicle escape systems.
基金Supported by the Natural Science Foundation of China under Grant No.10865006the Natural Science Foundation of Shaanxi Province under Grant No.2010JQ1014the Science Foundation of Baoji University of Science and Arts of China under Grant No.ZK0954
文摘The asymmetric effects on the escape rates from the stable states x±in the bistable system are analyzed. The results indicate that the multiplicative noise and the additive noise always enhance the particle escape from stable states x±of bistable.However,the asymmetric parameter r enhances the particle escape from stable state x_+,and holds back the particle escape from stable state x_-.
基金supported by the National Natural Science Foundation of China Fund(No 81541060)Science and Technology Projects from the Science Technology and Innovation Committee of Shenzhen Municipality(grant no.JCJY20170818110340383 and JCJY20170307163529489)。
文摘Antisense oligodeoxynucleotide(ASODN)can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing,in turn,plays antitumor therapeutic roles.In the study,a novel HIF-1αASODN-loaded nanocomposite was formulated to efficiently deliver gene to the target RNA.The physicochemical properties of nanocomposite were characterized using TEM,FTIR,DLS and zeta potentials.The mean diameter of resulting GEL-DGL-FA-ASODN-DCA nanocomposite was about 170–192 nm,and according to the agarose gel retardation assay,the loading amount of ASODN accounted for 166.7 mg/g.The results of cellular uptake showed that the nanocomposite could specifically target to HepG2 and Hela cells.The cytotoxicity assay demonstrated that the toxicity of vectors was greatly reduced by using DCA to reversibly block the cationic DGL.The subcellular distribution images clearly displayed the lysosomal escape ability of the DCA-modified nanocomposite.In vitro exploration of molecular mechanism indicated that the nanocomposite could inhibit m RNA expression and HIF-1αprotein translation at different levels.In vivo optical images and quantitative assay testified that the formulation accumulated preferentially in the tumor tissue.In vivo antitumor efficacy research confirmed that this nanocomposite had significant antitumor activity and the tumor inhibitory rate was 77.99%.These results manifested that the GEL-DGL-FA-ASODNDCA nanocomposite was promising in gene therapeutics for antitumor by interacting directly with target RNA.
文摘The relative escape rate (RER) in the bistable sawtooth system driven by correlated white noises was studied in the case of linear multiplicative noise coefficient.And we compare the RER of linear multiplicative noise coefficient with the RER of the piecewise constant multiplicative noise coefficient in the bistable sawtooth system,finally compare the RER of the bistable sawtooth potential with the RER of the quartic potential in the case of linear multiplicative noise coefficient.It can be seen that the form of the multiplicative noise coefficient and the nonlinearity of potential have an important influence on the resonant activation and the suppression of the RER.The resonant activation of the RER vanishes in the negative correlation when the multiplicative noise coefficient was shifted from piecewise constant to linear function in the bistable sawtooth potential.The suppression of the RER disappears in the negative correlation when thelinear potential is converted into nonlinear one.
基金supported by National Natural Science Foundation of China,SRF for ROCS,SEM,and K.C.Wong Magna Fund in Ningbo University
文摘A three-state Markovian noise is investigated.Its probability density and statistical properties are obtained. Escape of particles for a system with potential barrier only driven by this noise is investigated.It is shown that,in some circumstances,this noise can make the particles escape over the potential barrier;but in other circumstances,it cannot. Resonant activation phenomenon appears for the system considered by us.
文摘Despite the support of all kinds of fire prevention measures and high-tech fire prevention equipment,fires still occur frequently because of both anthro-pogenic factors and natural disasters.This issue has drawn the attention of schools,all levels of government,and other organizations.Many types of organi-zations carry out fire drills throughout the year.Because this kind of drill cannot anticipate the specific circumstances of each fire,which are generally far more complicated than drills,most people cannot correctly choose the optimal escape route from real fires.Thus,a fire-scene virtual simulation system based on the Dijkstra algorithm is here proposed to address such problems as casualties caused by frequent fires and the inability of most people to correctly choose a fire escape route.This virtual fire escape simulation system uses Maya to carry out 3D recon-struction of the fire scene,the Unity engine to conduct interactive function design,and the Dijkstra algorithm to calculate the best escape route.The results of the example indicate that the simulation system solves the problems of the traditional simulation system,such as stiffness,lack of intelligence,and poor simulation.
基金project was funded by the Foreign Youth Talent Program of the Ministry of Science and Technology of the People’s Republic of China(QN2023014004L)to Amaël BORZÉEa grant from the Korea Environmental Industry and Technology Institute(KEITI 2021002270001)to Yikweon JANGThe research was carried out whithin the state assignment of Ministry of Science and Higher Education of the Russian Federation(theme No.124012200182-1).
文摘Prey species may have their own optimal escape strategy to balance predation risks and the energetic cost of fleeing.Some species have an advantage when maintaining a short fleeing distance,while others may favour an earlier escape based on microhabitat,size,or body condition.Here,we examined the escape behaviour of the three syntopic Northeast Asian anuran species:Mongolian toads(Strauchbufo raddei),Amur brown frogs(Rana amurensis),and Japanese treefrogs(Dryophytes japonicus)in Mongolia,Russia,China and DPR Korea.We examined flight initiation distance(FID;the distance from a potential predator to the point when the individual starts to flee)and distance fled(DF;distance between flight initiation and flight termination points)of each species and the effects of microhabitat,sex,and body size.Strauchbufo raddei and R.amurensis had a longer FID than D.japonicus,and S.raddei also had a longer DF than D.japonicus.These trends remained similar when dividing FID and DF by a size proxy(snout-vent length)for all individuals.This suggests that the treefrog D.japonicus used a strategy to stay immobile even when they were detected,and the toad S.raddei reacted quicker and more sensitively to predators despite the presence of toxin.Female S.raddei had a significantly longer FID than males suggesting that females are more sensitive to predation risk in this species,but body size was not significant for any of the three species.Our results indicate that the three sympatric species have different escaping strategies,likely related to differences in physiology and crypticity.
文摘In the original publication of the article,the affiliation“College of Earth and Planetary Sciences,University of Chinese Academy of Sciences,Beijing,People’s Republic of China”for author Ziqi Wang was missing and included in this correction article.
基金Supported by a grant from National Natural Sciences Foundation of China (30240022).
文摘Objective: To investigate the expression of Fas, Fas ligand (FasL) and CD80 on the cell surface of mouse acute myelomonocytic leukemia cell line WEHI-3 and the function of FasL. Methods: The expression of Fas, FasL and CD80 was detected on WEHI-3 cell surface by flow cytometry. Simultaneously the function of FasL was determined by Thymidine (^3H-TdR) Incorporation. Results: The expression of CD80 and Fas on WEHI-3 cell surface was 5.06%±0.41% and 6.75%±2.31% (n=5) respectively, and the expression of FasL was up to 63.73%±5.23% (n=5). The apoptotic rate of YAC-1 cells was 26%±4.5%, 35%±3.2% and 43%±2.7% (n=5) respectively when WEHI-3 (effector cell, E) and Fas^+ YAC-1 cells (target cell, T) were cultured in the ratio of 3:1, 10:1 and 30:1. Conclusion: WEHI-3 cells express high FasL, low Fas and CD80, and can induce apoptosis of Fas^+ YAC-1 cells.
文摘Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.
基金National Basic Research Priorities Program of China(2011CB106303)The National Natural Science Foundation of China(31200699)The Fundamental Research Funds for the Central Universities(HUST:2012QN140)
文摘A 62-year-old man had chronic hepatitis B virus (HBV) infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient's virologic markers were positive for hepatitis B surface antigen (HBsAg), antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc), while antibody to hepatitis B surface antigen (anti-HBs) and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine (LMV) therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin (TB) were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C (HBsAg subtype adw) with immune escape mutations, F8L, $34L, F41S, G44V, F93C, V96G, Lll0I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.81873450)the Open Research Fund from Beijing Advanced Innovation Center for Big Data-Based Precision Medicine,Beijing Tongren Hospital,Beihang University&Capital Medical University(Grant No.BHTR-KFJJ-202009)The authors thank Life-Ontology Biological Technology Co.,Ltd for assistance with bioinfbrmatics analysis.
文摘Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Methods:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL.We identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell subtype.Subsequently,we identified cell markers,including a series of genes associated with immune escape and drug resistance.In addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL samples.Results:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B cells.The drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival promotion.Type III B cells closely communicate with other cells.The key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic value.Conclusion:This study investigated potential immune escape and drug resistance mechanisms in MCL.The results may guide individualized treatment and promote the development of therapeutic drugs.
文摘Alice Munro is one of the famous Canadian writers and is renowned above all for the astonishing subtlety of her short stories.Her theme has often been the dilemmas of the female coming to terms with family, friends in a small town. This paper attempts to make a brief introduction about the stories of Alice Munro's Runaway and explores the protagonist's choices in the dilemma situation, and then exposes the cruelty of reality is that they cannot get rid of the ineluctable reality of life. Escape is only a temporary action which cannot save them from endless triviality of life. What they should do is not to escape from life, but to adapt to the reality of life.
基金Supported by the National High Technology Research and Development Program of China (863 Program), No. 2002AA214061
文摘AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor escape.METHODS: Streptavidin-biotin-peroxidase immunohistochemistry technique was used to study the expression of Fas and FasL protein in 26 gallbladder carcinoma tissues,18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20 chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared with clinicopathological features of gallbladder carcinoma.RESULTS: The positive rates of Fas were not significantly different among carcinoma, adenoma, dysplasia and chronic cholecystitis. The positive rate of FasL in carcinoma was significantly higher than that in chronic cholecystitis (x2 = 4.89, P<0.05). The apoptotic index (AI) in carcinoma was significantly higher than that in adenoma (t'= 4.19, P<0.01) and chronic cholecystitis (t'= 8.06, P<0.01). The AI was significantly lower in well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma than that in poorly-differentiated carcinoma (t'= 2.63, P<0.05) and Nevin Ⅳ-Ⅴ carcinoma(t'= 3.33, P<0.01). The confidence interval (CI) ofinfiltrating lymphocytes in adenoma, chronic cholecystitis, well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma wasvery significantly lower than that in carcinoma (t' = 6.99,P<0.01), adenoma (t' = 3.66, P<0.01), poorly-differentiated carcinoma (t' = 5.31, P<0.01) and Nevin Ⅳ-Ⅴ carcinoma(t' = 3.76, P<0.01), respectively. The CI of apoptosis of infiltrating lymphocytes in well-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma (t = 2.52, P<0.05), and was not significantly lower in Nevin Ⅰ-Ⅲ carcinoma than in Nevin Ⅳ-Ⅴ carcinoma (t = 1.42, P>0.05). Apoptosis of infiltrating lymphocytes was not discovered in adenoma and chronic cholecystitis. CONCLUSION: FasL expressed in gallbladder carcinoma cells permits tumor cells to escape from immune surveillance of organism by inducing apoptosis in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma.
基金supported by a grant from Hubei Provin-cial Science and Technology Key Program Foundation of China (No. 2007AA402C60).
文摘B7-H1, a recently described member of the B7 family of costimulatory molecules, is thought to be involved in tumor immune escape by inducing T-cell apoptosis. In order to investigate the relationship between B7-H1 and immune escape of bladder cancer, B7-H1 expression in 50 cases of bladder cancer was detected by using immunohistochemical method. Survival curves were con- structed using the Kaplan-Meier method and independent prognostic factors were evaluated using the Cox regression model. Our results showed that the positive rate of B7-H1 immunostaining in normal bladder tissue and bladder cancer was 0 and 72% respectively. The expression of B7-H1 was strongly associated with the pathological grade, clinical stage and recurrence (P〈0.05). The survival rate was significantly lower in patients with B7-H1 positive group than in those with B7-H1 negative group and multi-variable analysis revealed that B7-H1 could be regarded as an independent factor in evaluating the prognosis of bladder cancer. It is concluded that the expression of B7-H1 is strongly associated with neoplastic progression and prognosis of bladder cancer. The manipulation of B7-H1 may become a beneficial target for immunotherapy in human bladder cancer.