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Abemaciclib-induced lung damage leading to discontinuation in brain metastases from breast cancer: A case report
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作者 Hiroyasu Yamashiro Nao Morii 《World Journal of Clinical Cases》 SCIE 2023年第35期8425-8430,共6页
BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estr... BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estrogen receptor-positive,HER2-negative breast cancer who developed brain metastasis.The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discon-tinuation due to drug-induced lung damage(DILD).CASE SUMMARY In this comprehensive case summary,we present the clinical course of a woman in her 60s,who 11 years following primary breast cancer surgery,was diagnosed with multiple brain metastases.As a third-line systemic therapy,she underwent treatment with abemaciclib and letrozole.This treatment approach yielded a near-partial response in her metastatic brain lesions.However,abemaciclib adminis-tration ceased due to the emergence of DILD,as confirmed by a computed tomography scan.The DILD improved after 1 mo of cessation.Despite ongoing therapeutic efforts,the patient’s condition progressively deteriorated,ultimately resulting in death due to progression of the brain metastases.CONCLUSION This case underscores the challenge of managing adverse events in responsive brain metastasis patients,given the scarcity of therapeutic options. 展开更多
关键词 Breast cancer HER2 negative Brain metastasis Abemaciclib Drug-induced interstitial lung damage Case report
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Effect of Tirapazamine and Mild Temperature Hyperthermia on the Recovery from Radiation-Induced Damage in Pimonidazole-Unlabeled Quiescent Tumor Cell Population
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作者 Shin-Ichiro Masunaga Yoshinori Sakurai +6 位作者 Hiroki Tanaka Minoru Suzuki Natsuko Kondo Masaru Narabayashi Keizo Tano Akira Maruhashi Koji Ono 《Journal of Cancer Therapy》 2013年第2期521-528,共8页
The aim in this study is to examine the effect of tirapazamine (TPZ) and mild temperature hyperthermia (MTH) on the repair of radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells. Labeling of p... The aim in this study is to examine the effect of tirapazamine (TPZ) and mild temperature hyperthermia (MTH) on the repair of radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells. Labeling of proliferating (P) cells in C57BL/6J mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after the administration of pimonidazole followed by TPZ treatment or MTH. Twenty-four hours later, assessment of the responses of Q and total (= P + Q) cells were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. With γ-rays only, the pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using a delayed assay, was more clearly observed in Q cells than total cells. Post-irradiation MTH more remarkably repressed the decrease in radio-sensitivity in the Q cell than the total cells. Post-irradiation TPZ administration produced a large radio-sensitizing effect on both total and Q cells, especially on Q cells. On the other hand, in pimonidazole-unlabeled cell fractions in both total and Q cells, TPZ suppressed the reduction in sensitivity due to delayed assay much more efficiently than MTH, whereas no radio-sensitizing effect was produced. Not only through suppressing the recovery from radiation-induced damage but also through radio-sensitizing effect, post-irradiation TPZ administration is very useful for repressing the increase in the difference in radio-sensitivity due to the delayed assay not only between total and Q tumor cells but also between the pimonidazole-unlabeled and the whole cell fractions within the total and Q tumor cells. 展开更多
关键词 Quiescent Cell RECOVERY from radiation-induced damage TIRAPAZAMINE PIMONIDAZOLE MILD TEMPERATURE HYPERTHERMIA
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Mechanisms of the alternative activation of macrophages and non-coding RNAs in the development of radiation-induced lung fibrosis 被引量:9
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作者 Nadire Duru Benjamin Wolfson Qun Zhou 《World Journal of Biological Chemistry》 CAS 2016年第4期231-239,共9页
Radiation-induced lung fibrosis(RILF) is a common side effect of thoracic irradiation therapy and leads to high mortality rates after cancer treatment. Radiation injury induces inflammatory M1 macrophage polarization ... Radiation-induced lung fibrosis(RILF) is a common side effect of thoracic irradiation therapy and leads to high mortality rates after cancer treatment. Radiation injury induces inflammatory M1 macrophage polarization leading to radiation pneumonitis, the first stage of RILF progression. Fibrosis occurs due to the transition of M1 macrophages to the anti-inflammatory pro-fibrotic M2 phenotype, and the resulting imbalance of macrophage regulated inflammatory signaling. Non-coding RNA signaling has been shown to play a large role in the regulation of the M2 mediated signaling pathways that are associated with the development and progression of fibrosis. While many studies show the link between M2 macrophages and fibrosis, there are only a few that explore their distinct role and the regulation of their signaling by non-coding RNA in RILF. In this review we summarize the current body of knowledge describing the roles of M2 macrophages in RILF, with an emphasis on the expression and functions of non-coding RNAs. 展开更多
关键词 MACROPHAGES M1 M2 Non-coding RNA MicroRNA Long-noncoding RNAs radiation-induced lung fibrosis FIBROSIS
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Correlation between miR-564, TGF-β1, and radiation-induced lung injury 被引量:4
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作者 Yunzhang Ge Tao Xie +5 位作者 Bin Yang Qianxia Li Qingrong Ren Xiaoyi Zhou Desheng Hu Zhongshu Tu 《Oncology and Translational Medicine》 2019年第5期204-210,共7页
Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-... Objective Our study aimed to analyze the expression of miR-564 and TGF-β1 in cancer tissues and the serum of patients with radiation-induced lung injury,and to investigate the relationship between them and radiation-induced lung injury.Methods In situ hybridization and real-time fluorescence quantitative method were used to detect the expression of miR-564.Additionally,immunohistochemistry and enzyme-linked immunosorbent assay(ELISA)were performed to detect the expression of TGF-β1.Results The overall incidence of acute radiation pneumonia was 55.9%(100/179).The incidence of≥grade 2 radioactive pneumonia was 24.0%(43/179)and that of grade 1 was 31.8%(57/179).The expression of miR-564 in grade≥2 was slightly higher than that in patients without or with grade 1,but there was no statistical difference(P=0.86).The serum level and ratio of miR-564 in patients with grade≥2 were significantly higher than those without or with grade 1(P=0.005,P=0.025,respectively).The expression of TGF-β1 in grade≥2 was significantly higher than that of patients without or with grade 1(P=0.017).The serum levels of TGF-β1 in grade≥2 were significantly higher than those in patients without or with grade 1(P=0.038).Although the ratio of TGF-β1 in radiation pneumonia of grade≥2 was significantly higher than that of without or with grade 1,there was no significant difference(P=0.24).Moreover,patients with higher expression of miR-564 and lower expression of TGF-β1 had better prognosis.Conclusion MiR-564 and TGF-β1 are predictors of radiation-induced lung injury.Monitoring its changing trend can improve the accuracy of predicting radiation-induced lung injury.The levels and ratio of serum miR-564 and TGF-β1 in patients with radiation-induced lung injury are related to the severity of radiationinduced lung injury. 展开更多
关键词 radiation-induced lung INJURY miR-564 TGF-Β1
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Perspectives on mesenchymal stem/progenitor cells and their derivates as potential therapies for lung damage caused by COVID-19 被引量:2
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作者 Aleksandra Klimczak 《World Journal of Stem Cells》 SCIE CAS 2020年第9期1013-1022,共10页
The new coronavirus,severe acute respiratory syndrome coronavirus-2(SARSCoV-2),which emerged in December 2019 in Wuhan,China,has reached worldwide pandemic proportions,causing coronavirus disease 2019(COVID-19).The cl... The new coronavirus,severe acute respiratory syndrome coronavirus-2(SARSCoV-2),which emerged in December 2019 in Wuhan,China,has reached worldwide pandemic proportions,causing coronavirus disease 2019(COVID-19).The clinical manifestations of COVID-19 vary from an asymptomatic disease course to clinical symptoms of acute respiratory distress syndrome and severe pneumonia.The lungs are the primary organ affected by SARS-CoV-2,with a very slow turnover for renewal.SARS-CoV-2 enters the lungs via angiotensinconverting enzyme 2 receptors and induces an immune response with the accumulation of immunocompetent cells,causing a cytokine storm,which leads to target organ injury and subsequent dysfunction.To date,there is no effective antiviral therapy for COVID-19 patients,and therapeutic strategies are based on experience treating previously recognized coronaviruses.In search of new treatment modalities of COVID-19,cell-based therapy with mesenchymal stem cells(MSCs)and/or their secretome,such as soluble bioactive factors and extracellular vesicles,is considered supportive therapy for critically ill patients.Multipotent MSCs are able to differentiate into different types of cells of mesenchymal origin,including alveolar epithelial cells,lung epithelial cells,and vascular endothelial cells,which are severely damaged in the course of COVID-19 disease.Moreover,MSCs secrete a variety of bioactive factors that can be applied for respiratory tract regeneration in COVID-19 patients thanks to their trophic,anti-inflammatory,immunomodulatory,anti-apoptotic,pro-regenerative,and proangiogenic properties. 展开更多
关键词 Mesenchymal stem cells Stem/progenitor cells lung damage Mesenchymal stem cell secretome COVID-19 disease COVID-19 pneumonia
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Markers of Heart, Lung and Dorsal Aorta Damage of Mother Rats and Their Neonates Post Therapeutic Treatment with Doxorubicin, Cisplatin and 5-Flurouracil 被引量:1
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作者 Heba A. El-Ghawet Abdelalim A. Gadallah +2 位作者 Ahmed A. El-Mansi Ali H. Amin Hassan I. H. El-Sayyad 《Chinese Medicine》 2017年第3期82-99,共18页
Aim: Recently, there is an increased average of developing cancers. Though, the chemotherapeutic-treatment is unfavorable during pregnancy due to its harmful effects on developing fetuses, physicians have two ways to ... Aim: Recently, there is an increased average of developing cancers. Though, the chemotherapeutic-treatment is unfavorable during pregnancy due to its harmful effects on developing fetuses, physicians have two ways to minimize these effects either by termination of the pregnancy or minimizing its side effects. The present work aimed to illustrate the susceptibility of cardiac, lung and dorsal aorta function to the widely applicable drugs doxorubicin and cisplatin as well as 5-flurouracil. Materials and Methods: Mother albino rats were arranged into four-groups (control, doxorubicin, cisplatin and 5-flurouracil-treated groups). Each pregnant rat received intraperitoneal administration of 0.2 mg/kg body weight at 10th and 14th day of gestation and sacrificed at parturition (two doses). At parturition, serum of mother rats used to assess troponin I, heat shock protein 70, 8-hydroxydeoxyguanosine, vascular endothelial growth factor and adhesion molecules (ICAM-1 & VCAM-1). Isoenzyme electrophoresis of alkaline and acid phosphatases, glucose-6-phosphate dehydrogenase and lactic dehydrogenase were estimated in serum, myocardium and dorsal aorta of mother rats. The myocardium and lung were processed for histopathological investigations for both mothers and their offspring. Single strand (comet assay) and double strand DNA damage were carried out in heart and dorsal aorta of mother rats. Results: The present finding revealed that there are detected alterations of myocardial markers and lung amino acid metabolism as well as disruption of myocardial isoenzymes. DNA damage of myocardium and dorsal aorta were observed. Conclusions: The authors concluded that the metabolic activity of heart and lung is highly susceptible to doxorubicin and cisplatin treatment compared to 5-flurouracil and the therapeutic doses must be degraded. 展开更多
关键词 Anticancer Drugs HEART lung Dorsal Aorta ISOENZYME Electrophoresis Biochemical MARKERS Amino Acids DNA damage
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Oleuropein alleviates sepsis-induced acute lung injury via the AMPK/Nrf-2/HO-1 signaling
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作者 Shan-Hu Wang Yang-Yang Wu Xiao-Jiao Xia 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2024年第5期187-198,共12页
Objective:To explore the effect of oleuropein on sepsis-induced acute lung injury(ALI)in vitro and in vivo and investigate the underlying mechanism.Methods:In an lipopolysaccharide(LPS)-mediated cell model of sepsis-i... Objective:To explore the effect of oleuropein on sepsis-induced acute lung injury(ALI)in vitro and in vivo and investigate the underlying mechanism.Methods:In an lipopolysaccharide(LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI,CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis.ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress,respectively.Western blot was applied to determine the expression of apoptosis-and AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor-2(Nrf-2)/heme oxygenase-1(HO-1)signaling-associated proteins.JC-1 staining,adenosine triphosphate(ATP)assay kit,and MitoSOX Red assays were performed to detect mitochondrial membrane potential,ATP content,and mitochondrial ROS formation,respectively.Moreover,lung injury was evaluated by measuring lung morphological alternations,lung wet-to-dry ratio,myeloperoxidase content,and total protein concentration.Results:Oleuropein reduced inflammatory reaction,oxidative damage,and apoptosis,and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI.Besides,oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway.However,these effects of oleuropein were abrogated by an AMPK inhibitor compound C.Conclusions:Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling,which might be a potential therapeutic agent for the treatment of sepsis-induced ALI. 展开更多
关键词 AMPK/Nrf-2/HO-1 signaling Inflammatory response lung damage Mitochondrial dysfunction OLEUROPEIN Oxidative stress SEPSIS
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Prevention and treatment of radiation-induced lung injury by hydroxypiperquin phosphate: a clinical and experimental study
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作者 闵碧荷 王梅 +2 位作者 肖作平 孟沛霖 蓝莉 《Journal of Medical Colleges of PLA(China)》 CAS 2000年第1期76-78,共3页
Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were ... Objective: To evaluate the hydroxypiperquin phosphate (HPQP) as a modifier of radiation-induced injury in human and rat lungs. Methods: Sixty-five patients with lung cancer treated with conventional radiotherapy were divided into 2 groups randomly: Thirty cases were treated with HPQP and the others were in a control group. The changes of X - ray manifestation before, after and during taking drug were compared. An animal model of radiation-induced fibrosis of lungs was also established. Hydroxyproling (HP) content in lung tissue and the pathological changes in rat lungs were checked with microscope and electron microscope after 4 months and 6 months respectively. Results: The changes of lung X-ray manifestation in treatment group were much lighter than that in control group. The HP content and the change of pathology in the lungs of those rats with HPQP treatment were obviously less than that in control group. Conclusion: HPQP plays an important role in prevention and treatment of radiation-induced injury in lungs. 展开更多
关键词 hydroxypiperquin PHOSPHATE radiation-induced lung INJURY
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Discussion on the Prevention and Treatment of COVID-19 Causing Lung Disease and Heart Damage Based on Lei Zhongyi's Theory of Intermingled Phlegm,Blood Stasis and Toxin
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作者 Jinfeng CHEN Zhongyi LEI +6 位作者 Chaofeng LIU Hong FAN Peng LEI Xueping WU Xiaoyong YU Yanfen ZHOU Jiejun HOU 《Medicinal Plant》 CAS 2020年第6期6-11,共6页
Novel coronavirus infection not only damages lung function,but also causes myocardial injury,elevated myocardial enzymes and heart failure,especially for patients with basic heart diseases who develop COVID-19,the fir... Novel coronavirus infection not only damages lung function,but also causes myocardial injury,elevated myocardial enzymes and heart failure,especially for patients with basic heart diseases who develop COVID-19,the first consideration should be the protection of cardiac function.Based on the theory of intermingled phlegm,blood stasis and toxin of heart disease put forward by Master Lei Zhongyi,the dialectical treatment thinking of COVID-19 patients from the concept of damage of phlegm,blood stasis and toxin to the heart were discussed.During the diagnosis,critical stage and recovery period of COVID-19,expectorant and blood-activating agents,heat and detoxification agents can be added to promote lung and asthma,free Bizheng and remove blood stasis,calm the heart and calm the mind,and promote the recovery of cardiopulmonary functions. 展开更多
关键词 COVID-19 Intermingled phlegm Blood stasis and toxin Lei Zhongyi lung disease and heart damage Blood stasis caused by epidemic toxin
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Extended damage range of(Al0.3Cr0.2Fe0.2Ni0.3)3O4 high entropy oxide films induced by surface irradiation
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作者 Jian-Cong Zhang Sen Sun +2 位作者 Zhao-Ming Yang Nan Qiu Yuan Wang 《Chinese Physics B》 SCIE EI CAS CSCD 2020年第6期374-378,共5页
Irradiation makes structural materials of nuclear reactors degraded and failed.However,the damage process of materials induced by irradiation is not fully elucidated,mostly because the charged particles only bombarded... Irradiation makes structural materials of nuclear reactors degraded and failed.However,the damage process of materials induced by irradiation is not fully elucidated,mostly because the charged particles only bombarded the surface of the materials(within a few microns).In this work,we investigated the effects of surface irradiation on the indirect irradiation region of the(Al0.3Cr0.2Fe0.2Ni0.3)3O4 high entropy oxide(HEO)films in detail by plasma surface interaction.The results show that the damage induced by surface irradiation significantly extends to the indirect irradiation region of HEO film where the helium bubbles,dislocations,phase transformation,and the nickel oxide segregation were observed. 展开更多
关键词 high entropy oxide films surface irradiation radiation-induced segregation VACANCIES extended irradiation damage region
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苍术素调节CXCL12/CXCR4信号通路对哮喘幼年大鼠肺组织损伤的影响
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作者 陈洋洋 马鸿琦 +2 位作者 杨静 吴宗跃 朱萍 《实用医学杂志》 CAS 北大核心 2024年第19期2672-2677,共6页
目的探讨苍术素调节CXC趋化因子配体12(CXCL12)/趋化因子受体4(CXCR4)信号通路对哮喘幼年大鼠肺组织损伤的影响。方法60只大鼠随机取12只SD幼年大鼠作为对照组(CON组),其余48只大鼠使用卵清蛋白(OVA)构建哮喘模型。将造模成功的哮喘大... 目的探讨苍术素调节CXC趋化因子配体12(CXCL12)/趋化因子受体4(CXCR4)信号通路对哮喘幼年大鼠肺组织损伤的影响。方法60只大鼠随机取12只SD幼年大鼠作为对照组(CON组),其余48只大鼠使用卵清蛋白(OVA)构建哮喘模型。将造模成功的哮喘大鼠随机平分为Model组、苍术素组(50 mg/kg苍术素)、CXCL-12组(5μg/kg重组CXCL-12蛋白)以及苍术素+CXCL-12组(50 mg/kg苍术素+5μg/kg重组CXCL-12蛋白),每组均12只,连续给药14 d,CON组和Model组给予等量生理盐水。收集支气管肺泡灌洗液(BALF)检测中性粒细胞、嗜酸粒细胞百分比。ELISA法检测血清和BALF液中细胞因子水平;HE染色检测肺组织病理变化;Western blot检测CXCL12/CXCR4通路相关蛋白水平。结果与CON组相比,Model组大鼠肺组织病理评分、中性粒细胞百分比、嗜酸粒细胞百分比、IL-17、IL-4、IL-5、IL-13、IgE、OVA sIgE水平以及CXCL12、CXCR4蛋白水平均显著增加(P<0.05);与Model组相比,苍术素组大鼠肺组织病理评分、中性粒细胞百分比、嗜酸粒细胞百分比、IL-17、IL-4、IL-5、IL-13、IgE、OVA sIgE以及CXCL12、CXCR4蛋白水平均显著降低(P<0.05),而CXCL-12组结果与苍术素组趋势相反;CXCL-12消除了苍术素对哮喘大鼠的改善效果。结论苍术素可能通过下调CXCL12/CXCR4信号通路对哮喘大鼠肺组织损伤起到改善作用。 展开更多
关键词 苍术素 CXCL12/CXCR4信号通路 哮喘 肺损伤
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柚皮素对肺结核大鼠肺组织损伤的影响及其机制
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作者 张璐 《山西医科大学学报》 CAS 2024年第4期466-472,共7页
目的探究柚皮素(NAR)对肺结核(PTB)大鼠肺组织损伤的影响及其机制。方法120只大鼠分为对照组(control)、模型组(PTB)、柚皮素低[25 mg/(kg·d)]、中[50 mg/(kg·d)]、高剂量[100 mg/(kg·d)]组和柚皮素高剂量+Colivelin[信... 目的探究柚皮素(NAR)对肺结核(PTB)大鼠肺组织损伤的影响及其机制。方法120只大鼠分为对照组(control)、模型组(PTB)、柚皮素低[25 mg/(kg·d)]、中[50 mg/(kg·d)]、高剂量[100 mg/(kg·d)]组和柚皮素高剂量+Colivelin[信号转导与转录激活因子3(STAT3)激活剂]组(NAR-H+Colivelin),每组20只。计算肺组织湿重/干重(W/D)比值;ELISA法检测干扰素-γ(IFN-γ)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平。苏木素-伊红(HE)染色观察肺组织病理变化;免疫组化检测α-平滑肌肌动蛋白(α-SMA)表达;Western blot检测IL-6和STAT3蛋白表达。结果与control组相比,PTB组肺组织损伤严重,肺泡结构紊乱、塌陷,有大量炎症细胞浸润,肺间质充血增厚;W/D比值、IL-6、IL-1β、TNF-α和IFN-γ、MDA水平及α-SMA、IL-6表达和STAT3磷酸化水平均增加(P<0.05),SOD和GSH-Px水平均降低(P<0.05)。与PTB组相比,NAR-L组、NAR-M组和NAR-H组大鼠肺组织损伤程度及炎症细胞浸润减轻;W/D比值、IL-6、IL-1β、TNF-α和IFN-γ、MDA水平及α-SMA、IL-6表达和STAT3磷酸化水平剂量依赖性降低(均P<0.05),SOD和GSH-Px水平剂量依赖性增加(均P<0.05)。Colivelin逆转了柚皮素对PTB大鼠肺组织损伤的保护作用(P<0.05)。结论柚皮素可能通过抑制IL-6/STAT3信号通路激活,改善肺结核大鼠肺组织损伤。 展开更多
关键词 柚皮素 白细胞介素-6/信号转导与转录激活因子3信号通路 肺结核 肺组织损伤 氧化应激 炎症
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耐辐射肺腺癌细胞模型的放射生物学鉴定
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作者 陈家靖 刘晏娜 +4 位作者 曾琴 金鑫 杨满意 廖明媚 赵劲风 《中国病理生理杂志》 CAS CSCD 北大核心 2024年第4期586-593,共8页
目的:体外构建耐辐射的肺腺癌细胞模型,研究与肿瘤细胞辐射抗性相关的生物学变化。方法:通过分次照射建立了耐辐射的肺腺癌细胞模型A549RR;将A549和A549RR细胞各随机分为两组,分别给予0和8 Gy辐照,检测亲本细胞与耐辐射细胞的增殖能力... 目的:体外构建耐辐射的肺腺癌细胞模型,研究与肿瘤细胞辐射抗性相关的生物学变化。方法:通过分次照射建立了耐辐射的肺腺癌细胞模型A549RR;将A549和A549RR细胞各随机分为两组,分别给予0和8 Gy辐照,检测亲本细胞与耐辐射细胞的增殖能力和对放疗的敏感性;在A549、A549RR和辐射抗性部分消失的A549RR´三个细胞系中分别设置顺铂治疗组、顺铂联合放射治疗组和空白对照组,检测细胞对化疗及联合放化疗的敏感性;同时利用流式细胞术分别检测A549和A549RR细胞在接受0和8 Gy辐照后的细胞周期变化和凋亡情况,使用彗星试验检测DNA损伤情况,检测活性氧(ROS)和8-羟基脱氧鸟苷(8-OHdG)水平,并对细胞进行衰老相关β-半乳糖苷酶染色。结果:与亲本A549细胞相比,A549RR细胞的辐射抗性显著增强(P<0.01),增殖能力显著下降(P<0.01),化疗前后细胞活力无显著差异。相比亲本A549细胞,处于G2/M期的A549RR细胞显著减少(P<0.01),处于S期的A549RR细胞显著增多(P<0.01);高剂量辐照后,亲本A549细胞发生S期阻滞,而A549RR细胞的细胞周期在辐照前后无显著差异。此外,A549RR细胞在接受辐照后相比A549细胞DNA损伤减少(P<0.01),ROS水平降低(P<0.01),辐照前后A549RR细胞中8-OHdG水平和凋亡率无显著差异;A549RR细胞中处于衰老的细胞多于亲本A549细胞(P<0.01)。结论:本研究通过构建耐辐射细胞模型,探究了放疗对耐辐射肺癌细胞存活的影响及其在细胞周期、DNA损伤、凋亡、衰老以及氧化应激水平方面的变化,并有助于进一步研究肺癌放疗抵抗机制。 展开更多
关键词 肺癌 辐射抗性 DNA损伤 细胞周期 细胞凋亡 细胞衰老
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定量CT肺密度在慢性阻塞性肺疾病急性加重患者气管插管中的预测价值
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作者 范继芳 张溱乐 +6 位作者 黄伟青 梁庆 曾量波 王锡达 张贤亮 陈淮 刘韵 《中国急救医学》 CAS CSCD 2024年第9期796-800,共5页
目的探讨定量CT肺密度在慢性阻塞性肺疾病急性加重(AECOPD)患者气管插管中的预测价值。方法回顾性分析广州医科大学附属第一医院急诊科2019年1月至2023年12月收治的78例AECOPD患者,依据住院期间接受不同类型的机械通气方式分为对照组(... 目的探讨定量CT肺密度在慢性阻塞性肺疾病急性加重(AECOPD)患者气管插管中的预测价值。方法回顾性分析广州医科大学附属第一医院急诊科2019年1月至2023年12月收治的78例AECOPD患者,依据住院期间接受不同类型的机械通气方式分为对照组(无创呼吸机辅助通气,n=50)和研究组(气管插管辅助通气,n=28),收集并分析两组一般资料、实验室检查和定量CT肺密度参数,通过多因素Logistic回归分析探索各因素对气管插管结局的影响程度,最后采用受试者工作特征(ROC)曲线分析定量CT肺密度参数对气管插管结局的预测价值。结果与对照组比较,研究组降钙素原(PCT)、低通气肺组织、无通气肺组织、受损肺组织百分率升高,二氧化碳分压(PaCO_(2))和氧合指数(PaO_(2)/FiO_(2))降低,差异均有统计学意义(P均<0.05)。多因素Logistic回归分析显示,受损肺组织[OR(95%CI)=1.207(1.030~1.415)]是AECOPD气管插管的危险因素(P<0.05)。Spearman相关性分析显示,受损肺组织与PaO_(2)/FiO_(2)呈负相关(r s=-0.516,P<0.001)。ROC曲线分析显示,受损肺组织[曲线下面积(AUC)=0.705]对AECOPD患者气管插管具有显著预测价值(P<0.05),截断值为11.5%。结论受损肺组织可预测AECOPD患者气管插管,为早期识别重症患者提供帮助。 展开更多
关键词 慢性阻塞性肺疾病急性加重 肺密度 气管插管 无创通气 受损肺组织
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从“圆运动失调-瘀毒致损”谈脓毒症肺损伤
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作者 张雪玲 邱占军 +4 位作者 黄迪 阮梽珅 梁明昊 许一飞 陈宪海 《辽宁中医杂志》 CAS 北大核心 2024年第10期12-14,共3页
脓毒症引起的急性肺损伤病情危重,病死率高,因其进展迅速,中医辨证治疗也有一定的困难。中医认为脓毒症肺损伤的核心病机为“瘀毒致损”,从彭子益的圆运动理论出发,重新认识瘀与毒的形成,认为瘀毒互结是圆运动失调所致,治疗应补虚泻实,... 脓毒症引起的急性肺损伤病情危重,病死率高,因其进展迅速,中医辨证治疗也有一定的困难。中医认为脓毒症肺损伤的核心病机为“瘀毒致损”,从彭子益的圆运动理论出发,重新认识瘀与毒的形成,认为瘀毒互结是圆运动失调所致,治疗应补虚泻实,提出清热解毒以降气、活血化瘀以行气、健补脾胃以运轴、温肾助阳散阴寒的治法来恢复气机的圆运动,为中医辨治脓毒症肺损伤提供新思路。 展开更多
关键词 脓毒症肺损伤 圆运动 瘀毒致损
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甘草酸能减轻小鼠肺炎病毒引起的小鼠肺脏损伤
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作者 刘芸 冯婷婷 +4 位作者 佟巍 郭智 李夏 孔琪 向志光 《实验动物与比较医学》 CAS 2024年第3期251-258,共8页
目的通过小鼠肺炎病毒(pneumonia virus of mice,PVM)感染近交系BALB/c小鼠建立病毒感染肺炎动物模型,观察PVM感染过程中促炎症警报素分子高迁移率族蛋白B1(high mobility group box 1,HMGB1)的变化,以及HMGB1抑制剂甘草酸(glycyrrhizic... 目的通过小鼠肺炎病毒(pneumonia virus of mice,PVM)感染近交系BALB/c小鼠建立病毒感染肺炎动物模型,观察PVM感染过程中促炎症警报素分子高迁移率族蛋白B1(high mobility group box 1,HMGB1)的变化,以及HMGB1抑制剂甘草酸(glycyrrhizic acid,GA)对小鼠肺脏感染损伤的在体干预作用。方法将3周龄的雌性BALB/c小鼠随机分为3组,每组6只。一组未经PVM感染,作为对照组(Control);另外两组先以1×10^(4)半数组织培养感染剂量(50%tissue culture infective dose,TCID_(50))/25μL剂量滴鼻接种PVM,然后分别给予GA生理盐水溶液灌胃(GA组)或单纯生理盐水灌胃(normal saline,NS组)处理,连续15 d。其间,观察并记录各组小鼠体重、外观等改变。在实验终点采集各组小鼠的肺脏组织样本,通过苏木精-伊红染色和免疫组织化学法检测小鼠肺脏组织内PVM和HMGB1蛋白的分布情况;通过实时荧光定量PCR法检测小鼠肺脏组织中HMGB1、Toll样受体4(Toll-like receptor 4,TLR-4)、晚期糖基化终产物特异性受体(advanced glycosylation end-product-specific receptor,AGER),以及白细胞介素(interleukin,IL)-1β、IL-2和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)等炎症因子的表达水平。结果与Control组相比,NS组小鼠6 d后体重显著下降(P<0.05),组织病理学结果显示其肺脏有明显的炎症病变,免疫组织化学结果显示HMGB1从细胞核释放至细胞质,实时荧光定量PCR结果显示HMGB1、IL-1β和IL-2的表达水平均显著上调(P<0.05);GA干预组的临床症状和体重无明显变化。而与NS组相比,GA干预组肺组织的病理损伤明显减轻,且肺组织中HMGB1、IL-1β、IL-2和干扰素γ(interferon-γ,IFN-γ)的表达水平显著下降(P<0.05),但AGER的表达水平显著增高(P<0.05)。结论PVM感染能引起明显的小鼠肺部炎症性病理损伤,而GA能有效减轻其损伤,其作用机制可能与激活HMGB1信号通路相关。 展开更多
关键词 甘草酸 高迁移率族蛋白B1 小鼠肺炎病毒 肺损伤 BALB/C小鼠
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肺保护性通气对老年全麻腹部手术患者术后认知及氧化损伤的影响
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作者 周群 刘珊 +1 位作者 林舜艳 孙鹏飞 《中国医学创新》 CAS 2024年第24期23-27,共5页
目的:探究肺保护性通气对老年全麻腹部手术患者术后认知及氧化损伤的影响。方法:将2022年1月—2023年12月江苏省苏北人民医院的80例老年全麻腹部手术患者根据随机数字表法分为两组,每组40例。对照组进行常规通气,观察组则进行肺保护性... 目的:探究肺保护性通气对老年全麻腹部手术患者术后认知及氧化损伤的影响。方法:将2022年1月—2023年12月江苏省苏北人民医院的80例老年全麻腹部手术患者根据随机数字表法分为两组,每组40例。对照组进行常规通气,观察组则进行肺保护性通气。比较两组术后的认知障碍发生率、肺部并发症发生率、手术前后的氧合功能状态[动脉血氧分压(PaO_(2))及氧合指数(OI)]、认知功能相关指标[血清经元特异性烯醇化酶(NSE)、S100钙结合蛋白B(S100B)及神经生长因子(NGF)]及氧化损伤指标[血清总抗氧化能力(TAC)、丙二醛(MDA)、超氧化物歧化酶(SOD)及活性氧(ROS)]。结果:观察组的术后认知障碍发生率及肺部并发症发生率均显著低于对照组,差异均有统计学意义(P<0.05)。术前,两组的氧合功能状态、认知功能相关指标及氧化损伤指标比较,差异均无统计学意义(P>0.05);术后1、3 d观察组的氧合功能状态及TAC、SOD均显著高于对照组,认知功能相关指标及MDA、ROS均显著低于对照组,差异均有统计学意义(P<0.05)。结论:肺保护性通气可有效控制老年全麻腹部手术患者的术后认知障碍及肺部并发症发生率,且对于氧化损伤的控制效果较好。 展开更多
关键词 肺保护性通气 老年患者 全麻 腹部手术 认知状态 氧化损伤
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PARP抑制剂Olaparib对非小细胞肺癌细胞的放疗增敏作用及其机制
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作者 王彤 邱凌平 +3 位作者 钱肖颖 洪卫卫 王勇 李勇 《南昌大学学报(医学版)》 2024年第4期19-23,28,共6页
目的探讨聚腺苷二磷酸核糖聚合酶(PARP)抑制剂Olaparib对人非小细胞肺癌(NSCLC)细胞的放疗增敏作用及其可能的发生机制。方法以人NSCLC细胞A549细胞系为研究对象,采用CCK-8实验检测不同药物浓度梯度对细胞的增殖抑制作用。选择对细胞10... 目的探讨聚腺苷二磷酸核糖聚合酶(PARP)抑制剂Olaparib对人非小细胞肺癌(NSCLC)细胞的放疗增敏作用及其可能的发生机制。方法以人NSCLC细胞A549细胞系为研究对象,采用CCK-8实验检测不同药物浓度梯度对细胞的增殖抑制作用。选择对细胞10%抑制浓度(IC10)作为后续实验的药物浓度,实验分为对照组、Olaparib组、单纯放疗组(RT组)、Olaparib联合放疗组(Olaparib+RT组)。通过克隆形成实验和EDU细胞增殖实验检测Olaparib联合放疗后的增敏效果,流式细胞术检测各组细胞周期分布,Western blot实验检测各组DNA损伤标志蛋白γ-H2AX的表达。结果Olaparib对A549细胞具有抑制作用且呈剂量依赖性;在处理A549细胞24 h后IC10为2.593μmol·L^(-1);Olaparib放疗增敏比为1.966。Olaparib+RT组A549细胞的增殖能力下降(P<0.01);Olaparib+RT组的G2/M期细胞占比高于对照组(46.0%vs 10.8%,P<0.05);且Olaparib+RT组细胞中γ-H2AX明显高于RT组(P<0.01)。结论Olaparib对人NSCLC细胞A549细胞系有着放疗增敏效果,其机制可能与影响细胞周期、增加放疗后细胞DNA双链断裂形成相关。 展开更多
关键词 非小细胞肺癌 聚腺苷二磷酸核糖聚合酶抑制剂 A549肺癌细胞 奥拉帕尼 放疗增敏 DNA损伤修复
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肺泡巨噬细胞自噬在急性肺损伤/急性呼吸窘迫综合征中的研究进展
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作者 李赋 张志明 +6 位作者 张茂福 黄邦荣 乔玉洁 沈雁云 祁义燕 冯周利 李爱玉 《中国急救医学》 CAS CSCD 2024年第11期1002-1006,共5页
急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是一种高发病率与高病死率的临床危重疾病。近年来众多研究发现,细胞自噬与ALI/ARDS肺部损伤密切相关。肺泡巨噬细胞自噬在ALI/ARDS病程中具有重要调节作用,能够有效干预ALI/ARDS病程。结合文... 急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是一种高发病率与高病死率的临床危重疾病。近年来众多研究发现,细胞自噬与ALI/ARDS肺部损伤密切相关。肺泡巨噬细胞自噬在ALI/ARDS病程中具有重要调节作用,能够有效干预ALI/ARDS病程。结合文献研究发现,肺泡巨噬细胞自噬调节是减轻ALI/ARDS的重要靶点,能够有效减轻肺损伤。本研究主要对肺泡巨噬细胞自噬在ALI/ARDS中的双重靶向调节作用研究进展进行综述,以期为今后ALI/ARDS的临床治疗提供新的研究思路和方向。 展开更多
关键词 急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS) 肺泡巨噬细胞 自噬 肺部损伤 调节作用
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免疫原性细胞死亡在肺癌治疗中的研究进展
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作者 李健伦 黄思剑 +6 位作者 牟漫 卫向红 操媛 王丽娟 卓可星 李旭 钟茂华 《华中科技大学学报(医学版)》 CAS CSCD 北大核心 2024年第4期552-557,共6页
肺癌是一种发病率和致死率均较高的恶性肿瘤,具有分型多、恶性程度高及预后不良等特点。免疫疗法通过激发和增强机体的免疫功能,达到控制和杀伤肿瘤细胞的目的,已被证实对多种类型的恶性肿瘤具有良好的治疗效果。免疫原性细胞死亡(immun... 肺癌是一种发病率和致死率均较高的恶性肿瘤,具有分型多、恶性程度高及预后不良等特点。免疫疗法通过激发和增强机体的免疫功能,达到控制和杀伤肿瘤细胞的目的,已被证实对多种类型的恶性肿瘤具有良好的治疗效果。免疫原性细胞死亡(immunogenic cell death,ICD)是一种程序性细胞死亡方式,其特点是损伤相关分子模式(damage-associated molecular patterns,DAMPs)的大量释放。在经过某些化疗药物、物理疗法、生物疗法或联合治疗后,肺癌细胞会发生ICD,由非免疫原性转变为免疫原性,进而募集和活化免疫细胞,最终激活和增强机体抗肿瘤免疫应答。该文就ICD的发生机制以及ICD在肺癌治疗中的应用作一综述。 展开更多
关键词 肺癌 免疫原性细胞死亡 损伤相关分子模式 ICD诱导剂
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