Introduction: The occurrence of intrauterine fetal death (IUFD) is a traumatic event not only for the mother and her family but also for the obstetric team. IUFD is a common event. Objective: the aim of our study is t...Introduction: The occurrence of intrauterine fetal death (IUFD) is a traumatic event not only for the mother and her family but also for the obstetric team. IUFD is a common event. Objective: the aim of our study is to describe the epidemiological, diagnostic and management aspects of IUFD at the Sylvanus Olympio University Teaching Hospital (CHU SO), Lomé. Methodology: It was a descriptive cross-sectional study with retrospective data collection process that concerned cases of IUFD from January 1st 2023 to December 31, 2023 at CHU SO. Results: The hospital prevalence of IUFD was 2.43%. The mean age of the mothers was 30.6 ± 6 years. The Multigestures represented 32.52% and primiparous women represented 29.72%. Pregnant women were referred in 88.11% of cases;47.55% had done at least 4 antenatal care visits and 4.20% had a history of IUFD. The etiological factors of IUFD were preeclampsia in 28.67% of cases, retroplacental hematoma in 28.67% and premature rupture of membranes in 4.55% of cases. Misoprostol was used for artificial induction of labor in 57.14% of cases and the delivery route was vaginal in 75.87% of cases. Conclusion: The frequency of IUFD is high and its reduction remains a challenge in low-income countries.展开更多
BACKGROUND Acute pancreatitis in pregnancy is a rare but serious condition that can lead to high maternal mortality and fetal loss.Instances of pregnancy complicated by severe acute pancreatitis,particularly with subs...BACKGROUND Acute pancreatitis in pregnancy is a rare but serious condition that can lead to high maternal mortality and fetal loss.Instances of pregnancy complicated by severe acute pancreatitis,particularly with subsequent respiratory and cardiac arrest,are rarely reported.CASE SUMMARY We present the case of a 35-year-old woman,at 36+5 weeks of gestation,who presented with paroxysmal epigastric pain accompanied by low back pain,nausea,and vomiting.According to the clinical symptoms,B-ultrasound imaging and biochemical indicators,the patient was diagnosed with acute pancreatitis and initially managed conservatively.However,3 hours after admission,the patient experienced respiratory and cardiac arrest,and the fetus died.In this case,the adverse outcomes occurred due to the lack of aggressive fluid resuscitation and an active surgical intervention.CONCLUSION Implementing aggressive fluid resuscitation to sustain tissue perfusion,alongside the proactive evaluation of pharmacological agents that suppress gastric acid secretion and inhibit pancreatic enzyme activity,may be beneficial in mitigating the risk of a severely adverse prognosis.Effective management of acute pancreatitis during pregnancy requires careful timing of surgical intervention,a thorough evaluation of the risks and benefits regarding the continuation or termination of pregnancy,and a focus on safeguarding both maternal and fetal health.展开更多
Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th...BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.展开更多
Expressionism was an aesthetic movement originated in painting in the early 1920’s. But it has also exerted great influence on other forms of arts, including dramatic works. This paper intends to compare the applicat...Expressionism was an aesthetic movement originated in painting in the early 1920’s. But it has also exerted great influence on other forms of arts, including dramatic works. This paper intends to compare the application of expressionistic devices such as flashbacks, and the use of symbols and music in Death of a Salesman and The Glass Menagerie.展开更多
This thesis,by analyzing the wolf nature,the dog nature and the human nature,and their relations,expounds the author's personal interpretation of the theme of Sherwood Anderson's short story Death in the Woods...This thesis,by analyzing the wolf nature,the dog nature and the human nature,and their relations,expounds the author's personal interpretation of the theme of Sherwood Anderson's short story Death in the Woods.The author maintains that Anderson reveals to readers the ugliness of life and the strange beauty of life,condemns the loss of love and the dehumanization of human life in the modern world and implies Anderson's deep concern on the human alienation,an important theme in the 20th century modern literature.展开更多
"I regard the theater as a serious business, one that makes or should make man more human, which is to say, less alone."A great playwright of social philosophy, Arthur Miller advocates that the common man, a..."I regard the theater as a serious business, one that makes or should make man more human, which is to say, less alone."A great playwright of social philosophy, Arthur Miller advocates that the common man, and none of rank, is the tragic hero of modern times. His plays have always revealed before the public eyes the tragedy of the average American life, the psychology of the ordinary people, and their conflicts with the morality of society.展开更多
"Death of a Salesman"is important not only in its contents, but also in its creative techniques. This paper will focus on Miller's specific methods with which he depicts Willy's inner world. To be ex..."Death of a Salesman"is important not only in its contents, but also in its creative techniques. This paper will focus on Miller's specific methods with which he depicts Willy's inner world. To be exact, he borrowed some techniques from the films to achieve a free exchange of space and time, that is, to make Willy's remembrance and illusion audio-visual, making the play characteristic of the films.展开更多
Death of a Salesman is the greatest masterpiece of Arthur Miller.The play is about a common man trying to reach his American dream and the disillusionment of his dream.This paper mainly analyzes the symbols that are u...Death of a Salesman is the greatest masterpiece of Arthur Miller.The play is about a common man trying to reach his American dream and the disillusionment of his dream.This paper mainly analyzes the symbols that are used in the play to embody the theme.展开更多
Most of Nathaniel Hawthorne's masterpieces are created with the theme of morality,and are used to analysis and reveal"good and evil human nature"through the methods of profound symbolism and delicate psy...Most of Nathaniel Hawthorne's masterpieces are created with the theme of morality,and are used to analysis and reveal"good and evil human nature"through the methods of profound symbolism and delicate psychological description. To reemerge the spirit of The Scarlet Letter,Which is considered as Hawthorne's religious view and humanistic feeling,the death of two heroes in this novel should be analyzed in the aspects of religion and human nature,and even in the aspects of the vocabulary,theme and mental world of main characters.展开更多
Death of a Salesman,American playwright Arthur Miller 's masterpiece,describes the tragic fate of Willy Loman,a middle-class salesman.Some critics claim that the play is an attack upon the"American dream"...Death of a Salesman,American playwright Arthur Miller 's masterpiece,describes the tragic fate of Willy Loman,a middle-class salesman.Some critics claim that the play is an attack upon the"American dream"and that Willy is the victim of brutal economic system.However,on further studying the play,the writer draws the conclusion that Willy is not so much a victim of "American dream"as he is the victim of his own weakness in personality.展开更多
We examined how reactive oxygen species, in the form of hydrogen peroxide (H2O2), affect osmotic stress–induced programmed cell death during somatic embryogenesis from cotyledon explants of Manchurian ash (Fraxinus m...We examined how reactive oxygen species, in the form of hydrogen peroxide (H2O2), affect osmotic stress–induced programmed cell death during somatic embryogenesis from cotyledon explants of Manchurian ash (Fraxinus mandshurica Rupr.). We found that substantial osmotic stress was essential for Manchurian ash somatic cells to obtain embryogenic competence. The explant cells displayed hallmarks of programmed cell death, chromatin condensation, and DNA fragmentation to oligonucleotides during somatic embryogenesis. Increasing concentrations of plant growth regulators and sucrose in the medium increased osmotic stress thereby inducing H2O2 accumulation in the explant cells. We found that H2O2 concentration was significantly decreased in explant cells when the induction medium was modified, i.e., when reducing the concentration of sucrose, which reduces the osmotic pressure of the medium, or by withdrawing plant growth regulators at mid-culture. These treatments also decreased the proportion of explant cells undergoing programmed cell death. Accordingly, a decreased rate of somatic embryo induction was observed. These results show that PCD occurred during tissue browning and death of some explant cells during somatic embryogenesis in F. mandshurica. The ROS contributed to PCD in abiotic stress stimulated F. mandshurica cells.展开更多
Objective To investigate the expression of programmed cell death 5 (PDCD5) in tissues of normal human prostate (NP), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) in order to assess the clinica...Objective To investigate the expression of programmed cell death 5 (PDCD5) in tissues of normal human prostate (NP), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) in order to assess the clinical role of PDCD5 in PCa. Methods PDCD5 expression was determined by EnVision immunohistochemical staining in forma-lin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP, 22 with BPH, and 22 with PCa. In addition, PCa cases were classified as low/middle-risk (Gleason sumS7) and high-risk (Gleason sum〉7) on the basis of Gleason grade. Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique. Expression of PDCD5 was compared among different prostatic tissues. Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH (P〈0.01). However, there was no significant difference in PDCD5 expression between tissues of NP and BPH. In addition, the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa. Conclusions By downregulating apoptosis, low PDCD5 expression may play an important role in the occurrence and development of PCa. PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.展开更多
In Death of a Traveling Salesman,Eudora Welty's idyllic view on life in the countryside,her nostalgic feelings for the loss of the American Southern tradition,and her protest against the industrialization of the c...In Death of a Traveling Salesman,Eudora Welty's idyllic view on life in the countryside,her nostalgic feelings for the loss of the American Southern tradition,and her protest against the industrialization of the city life are demonstrated by compar ing the"alone"of the couple in the countryside and the"lonely"of R. J. Bowman as a traveling salesman in the city.展开更多
AIM To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism.METHODS Human hepatocel...AIM To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism.METHODS Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species(ROS) were quantified using the fluorescent probe DCFH-DA.RESULTS Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3 II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation.CONCLUSION Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.展开更多
文摘Introduction: The occurrence of intrauterine fetal death (IUFD) is a traumatic event not only for the mother and her family but also for the obstetric team. IUFD is a common event. Objective: the aim of our study is to describe the epidemiological, diagnostic and management aspects of IUFD at the Sylvanus Olympio University Teaching Hospital (CHU SO), Lomé. Methodology: It was a descriptive cross-sectional study with retrospective data collection process that concerned cases of IUFD from January 1st 2023 to December 31, 2023 at CHU SO. Results: The hospital prevalence of IUFD was 2.43%. The mean age of the mothers was 30.6 ± 6 years. The Multigestures represented 32.52% and primiparous women represented 29.72%. Pregnant women were referred in 88.11% of cases;47.55% had done at least 4 antenatal care visits and 4.20% had a history of IUFD. The etiological factors of IUFD were preeclampsia in 28.67% of cases, retroplacental hematoma in 28.67% and premature rupture of membranes in 4.55% of cases. Misoprostol was used for artificial induction of labor in 57.14% of cases and the delivery route was vaginal in 75.87% of cases. Conclusion: The frequency of IUFD is high and its reduction remains a challenge in low-income countries.
文摘BACKGROUND Acute pancreatitis in pregnancy is a rare but serious condition that can lead to high maternal mortality and fetal loss.Instances of pregnancy complicated by severe acute pancreatitis,particularly with subsequent respiratory and cardiac arrest,are rarely reported.CASE SUMMARY We present the case of a 35-year-old woman,at 36+5 weeks of gestation,who presented with paroxysmal epigastric pain accompanied by low back pain,nausea,and vomiting.According to the clinical symptoms,B-ultrasound imaging and biochemical indicators,the patient was diagnosed with acute pancreatitis and initially managed conservatively.However,3 hours after admission,the patient experienced respiratory and cardiac arrest,and the fetus died.In this case,the adverse outcomes occurred due to the lack of aggressive fluid resuscitation and an active surgical intervention.CONCLUSION Implementing aggressive fluid resuscitation to sustain tissue perfusion,alongside the proactive evaluation of pharmacological agents that suppress gastric acid secretion and inhibit pancreatic enzyme activity,may be beneficial in mitigating the risk of a severely adverse prognosis.Effective management of acute pancreatitis during pregnancy requires careful timing of surgical intervention,a thorough evaluation of the risks and benefits regarding the continuation or termination of pregnancy,and a focus on safeguarding both maternal and fetal health.
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo.
文摘Expressionism was an aesthetic movement originated in painting in the early 1920’s. But it has also exerted great influence on other forms of arts, including dramatic works. This paper intends to compare the application of expressionistic devices such as flashbacks, and the use of symbols and music in Death of a Salesman and The Glass Menagerie.
文摘This thesis,by analyzing the wolf nature,the dog nature and the human nature,and their relations,expounds the author's personal interpretation of the theme of Sherwood Anderson's short story Death in the Woods.The author maintains that Anderson reveals to readers the ugliness of life and the strange beauty of life,condemns the loss of love and the dehumanization of human life in the modern world and implies Anderson's deep concern on the human alienation,an important theme in the 20th century modern literature.
文摘"I regard the theater as a serious business, one that makes or should make man more human, which is to say, less alone."A great playwright of social philosophy, Arthur Miller advocates that the common man, and none of rank, is the tragic hero of modern times. His plays have always revealed before the public eyes the tragedy of the average American life, the psychology of the ordinary people, and their conflicts with the morality of society.
文摘"Death of a Salesman"is important not only in its contents, but also in its creative techniques. This paper will focus on Miller's specific methods with which he depicts Willy's inner world. To be exact, he borrowed some techniques from the films to achieve a free exchange of space and time, that is, to make Willy's remembrance and illusion audio-visual, making the play characteristic of the films.
文摘Death of a Salesman is the greatest masterpiece of Arthur Miller.The play is about a common man trying to reach his American dream and the disillusionment of his dream.This paper mainly analyzes the symbols that are used in the play to embody the theme.
文摘Most of Nathaniel Hawthorne's masterpieces are created with the theme of morality,and are used to analysis and reveal"good and evil human nature"through the methods of profound symbolism and delicate psychological description. To reemerge the spirit of The Scarlet Letter,Which is considered as Hawthorne's religious view and humanistic feeling,the death of two heroes in this novel should be analyzed in the aspects of religion and human nature,and even in the aspects of the vocabulary,theme and mental world of main characters.
文摘Death of a Salesman,American playwright Arthur Miller 's masterpiece,describes the tragic fate of Willy Loman,a middle-class salesman.Some critics claim that the play is an attack upon the"American dream"and that Willy is the victim of brutal economic system.However,on further studying the play,the writer draws the conclusion that Willy is not so much a victim of "American dream"as he is the victim of his own weakness in personality.
基金supported by the National Key R&D Program of China(2017YFD0600600)the National Natural Science Foundation of China(Nos.31400535 and 31570596)+2 种基金the National Basic Science Personnel Training Fund of China(No.J1210053)the Innovation Project of State Key Laboratory of Tree Genetics and Breeding(Northeast Forestry University,No.2016C01)the Fundamental Research Funds for the Central Universities(Nos.2572014CA13 and 2572018BW02)
文摘We examined how reactive oxygen species, in the form of hydrogen peroxide (H2O2), affect osmotic stress–induced programmed cell death during somatic embryogenesis from cotyledon explants of Manchurian ash (Fraxinus mandshurica Rupr.). We found that substantial osmotic stress was essential for Manchurian ash somatic cells to obtain embryogenic competence. The explant cells displayed hallmarks of programmed cell death, chromatin condensation, and DNA fragmentation to oligonucleotides during somatic embryogenesis. Increasing concentrations of plant growth regulators and sucrose in the medium increased osmotic stress thereby inducing H2O2 accumulation in the explant cells. We found that H2O2 concentration was significantly decreased in explant cells when the induction medium was modified, i.e., when reducing the concentration of sucrose, which reduces the osmotic pressure of the medium, or by withdrawing plant growth regulators at mid-culture. These treatments also decreased the proportion of explant cells undergoing programmed cell death. Accordingly, a decreased rate of somatic embryo induction was observed. These results show that PCD occurred during tissue browning and death of some explant cells during somatic embryogenesis in F. mandshurica. The ROS contributed to PCD in abiotic stress stimulated F. mandshurica cells.
文摘Objective To investigate the expression of programmed cell death 5 (PDCD5) in tissues of normal human prostate (NP), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) in order to assess the clinical role of PDCD5 in PCa. Methods PDCD5 expression was determined by EnVision immunohistochemical staining in forma-lin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP, 22 with BPH, and 22 with PCa. In addition, PCa cases were classified as low/middle-risk (Gleason sumS7) and high-risk (Gleason sum〉7) on the basis of Gleason grade. Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique. Expression of PDCD5 was compared among different prostatic tissues. Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH (P〈0.01). However, there was no significant difference in PDCD5 expression between tissues of NP and BPH. In addition, the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa. Conclusions By downregulating apoptosis, low PDCD5 expression may play an important role in the occurrence and development of PCa. PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.
文摘In Death of a Traveling Salesman,Eudora Welty's idyllic view on life in the countryside,her nostalgic feelings for the loss of the American Southern tradition,and her protest against the industrialization of the city life are demonstrated by compar ing the"alone"of the couple in the countryside and the"lonely"of R. J. Bowman as a traveling salesman in the city.
基金Supported by Science and Technology Program of Chongqing,No.2013-2-179
文摘AIM To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism.METHODS Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species(ROS) were quantified using the fluorescent probe DCFH-DA.RESULTS Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3 II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation.CONCLUSION Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.