In this work, lateral deformation of human eosinophil cell during the lateral indentation by an optically trapped microbead of diameter 4.5 µm is studied. The images were captured using a CCD camera and the Boltz...In this work, lateral deformation of human eosinophil cell during the lateral indentation by an optically trapped microbead of diameter 4.5 µm is studied. The images were captured using a CCD camera and the Boltzmann statistics method was used for force calibration. Using the Hertz model, we calculated and compared the elastic moduli resulting from the lateral force, showing that the differences are important and the force should be considered. Besides the lateral component, the setup also allows us to examine the lateral cell-bead interaction. The mean values of the properties obtained, in particular the elastic stiffness and the shear stiffness, were Eh = (37.76 ± 2.85) µN/m and Gh = (12.57 ± 0.32) µN/m. These results show that the lateral indentation can therefore be used as a routine method for cell study, because it enabled us to manipulate the cell without contact with the laser.展开更多
BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequat...BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.展开更多
There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation...There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.展开更多
Summary： In order to study whether cysteine-rich 61 protein （cyr61） is involved in the pathogenesis of asthma and its relation to airway inflammation, the effect of dexamethasone （Dxm） on the expression of cyr61 ...Summary： In order to study whether cysteine-rich 61 protein （cyr61） is involved in the pathogenesis of asthma and its relation to airway inflammation, the effect of dexamethasone （Dxm） on the expression of cyr61 in the lung tissues of asthmatic mice was investigated. Forty BALB/c mice were divided into asthma group （n=15）, control group （n=10） and Dxm group （n=15）. The asthma group was sensitized and challenged by ovalbumin （OVA）. The mice in Dxm group were intraperitoneally administered with Dxm after OVA challenge. The expression of cyr61 in the lung tissues was detected by using immuno- histochemistry, and that of eotaxin protein in the bronchoalveolar lavage fluid （BALF） by using en- zyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in BALF was also ana- lyzed. The results showed that the cyr61 expression was highest in asthma group （P〈0.05）, followed by Dxm group （P〈0.05） and control group. The cyr61 had a positive correlation with the total nucleated cells （r=0.867, P〈0.05）, especially eosinophils （r=0.856, P〈0.05）, and eotaxin level （r=0.983, P〈0.05） in the BALF. Our findings suggested that cyr61 is expressed in airway epithelial cells and has a positive correlation with eotaxin and number of airway infiltrating eosinophils.展开更多
Langerhans cell histiocytosis(LCH) is a rare condition mostly seen in children and adolescents. Eosinophilic granuloma(EG) is one of its three clinical entities and is considered as a benign osteolytic lesion. Many re...Langerhans cell histiocytosis(LCH) is a rare condition mostly seen in children and adolescents. Eosinophilic granuloma(EG) is one of its three clinical entities and is considered as a benign osteolytic lesion. Many reports of patients with spine histiocytosis are well documented in the literature but it is not the case of atlantoaxial localization. We report here a new observation of atlantoaxial LCH in a 4-year-old boy revealed by persistent torticollis. He was successfully treated with systemic chemotherapy and surgery. Inter-body fusion packed by autologous iliac bone was performed with resolution of his symptoms. It is known that conservative treatment is usually sufficient and surgery should be reserved for major neurologic defects in spine EG. In atlantoaxial lesion, surgical treatment should be frequently considered.展开更多
Background:Nuclear factor kappa B(NF-kappa B) overactivation plays a crucial role in T-helper 2 (Th2)-biased allergic airway inflammation by increased activation and decreased apoptosis of CD4(+) T cells. We have show...Background:Nuclear factor kappa B(NF-kappa B) overactivation plays a crucial role in T-helper 2 (Th2)-biased allergic airway inflammation by increased activation and decreased apoptosis of CD4(+) T cells. We have shown that targeted NF-kappa B suppression in dendritic cells by adenoviral gene transfer of a novel mutated inhibitor of NF-kappa B(I kappa B alpha) (AdI kappa B alpha M) contributes to T-cell tolerance, but the immunosuppressive action of AdI kappa B alpha M on memory(CD45RO(+)) CD4(+) T cells remains enigmatic. Methods:CD45RO(+) T cells from Dermatophagoides farinaei-sensitized asthmatic patients, untransfected or transfected with AdI kappa B alpha M or AdLacZ(beta-galactosidase) for 24 h, were stimulated with anti-CD3(1.0 mu g/ml) plus anti-CD28(0.5 mu g/ml) monoclonal antibody for an additional 24 h. I kappa B alpha M transgene expression and NF-kappa B activation were detected by polymerase chain reaction(PCR), reverse transcription-PCR(RT-PCR), Western blot analysis, and electrophoretic mobility shift assay. Phenotype and apoptosis were measured by flow cytometry, annexin V binding, and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling analyses. Cytokine production and cell proliferation were determined using enzyme-linked immunosorbent assay andH-3 thymidine incorporation. Results:A unique 801-bp I kappa B alpha M cDNA and a dose-dependent increase in I kappa B alpha M transgene expression were observed in AdI kappa B alpha M-transfected CD45RO(+) T cells. Significantly, AdI kappa B alpha M inhibited CD3/CD28-mediated NF-kappa B activation in CD45RO(+) T cells, leading to evident apoptosis, reduction of eotaxin, RANTES, Th1 interferon (IFN)-gamma and interleukin (IL)-2, and Th2 (IL-4, IL-5, and IL-13 despite a slight decrease in IL-10) cytokines and secondary proliferative response. AdI kappa B alpha M also upregulated cytotoxic T lymphocyte-associated antigen 4(CTLA-4) and downregulated CD69 besides no change in CD28. Conclusion:I kappa B alpha M might be beneficial to augment memory CD4(+) T-cell tolerance through modulating B7-CD28/CTLA-4 co-stimulatory pathways and NF-kappa B-dependent cytokine profiles in allergic inflammatory diseases including asthma.展开更多
Introduction: Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized bone marrow-derived Langerhans cells (LCs) and mature eosinophils, resulting in so...Introduction: Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized bone marrow-derived Langerhans cells (LCs) and mature eosinophils, resulting in solitary or few, indolent and chronic, lesions of bone or other organs called eosinophilic granulomas. Calvarial LCH is quite rare and an underappreciated differential etiology of skull lesions. We present a most unusual case of a young child with hyperacutely symptomatic langerhans histiocytosis of the skull. Method: A 7-year-old male presented with a history of increasing (progressive) frontal headaches of 8 days duration, unaccompanied by associated nausea, vomiting, or diplopia. His only additional complaint was a hard bump on his forehead. MRI and CT done in the ER identified a right fronto-parietal lesion with associated skull erosion. Nuclear medicine and SPECT studies confirmed an erosive skull lesion without significant metabolic activity. A right frontal craniectomy and excision was performed. Results: A soft, rubbery well-circumcised mass coming from the diploic layer of the skull with involvement of bone was identified. The mass had eroded both the outer and inner table of the skull, and the involved area of the right frontal bone was resected. Intra-operative histo-pathologic analysis of the lesion revealed Langerhans cell histiocytosis without involvement of the dura. The patient experienced no neurological worsening as a result of the resection. He was discharged home in stable condition. Conclusion: LCH lesions of the skull are common findings, however, this focal hyperacute symptomatic presentation is most rare and should not deter us from anticipating an erosive bony tumor and planning timely surgical management.展开更多
目的外周血免疫细胞计数与胃癌的发生发展以及胃癌患者的预后之间的联系往往易受到反向因果关系和混杂因素的影响,研究旨在运用孟德尔随机化分析排除相关偏倚,阐明外周免疫细胞计数和胃癌的因果关系。方法主要采用单因素和多因素孟德尔...目的外周血免疫细胞计数与胃癌的发生发展以及胃癌患者的预后之间的联系往往易受到反向因果关系和混杂因素的影响,研究旨在运用孟德尔随机化分析排除相关偏倚,阐明外周免疫细胞计数和胃癌的因果关系。方法主要采用单因素和多因素孟德尔随机化的方法,利用全基因组关联研究(genomewide association study,GWAS)数据,探究外周血中各免疫细胞亚型与胃癌发生风险之间的因果关系。将白细胞、粒细胞、中性粒细胞、嗜酸性粒细胞、嗜碱性粒细胞、淋巴细胞、单核细胞计数作为暴露因素,选用逆方差加权法作为单变量孟德尔随机化分析的主要方法。随后进行了两步法中介分析,探究血浆蛋白可能起到的作用。结果淋巴细胞(OR=1.094,95%CI:1.009~1.185,P=0.029)、嗜酸性粒细胞(OR=0.881,95%CI:0.813~0.955,P=0.002)与胃癌之间存在因果关系,敏感性分析进一步证实了此结果的可靠性。而嗜酸性粒细胞降低胃癌发生风险之间的关联在多变量孟德尔随机化分析中仍然显著(OR=0.807,95%CI:0.671~0.970,P=0.023),反向因果关系不显著。酸性富含半胱氨酸分泌蛋白(secreted protein acidic and rich in cysteine,SPARC)是一种细胞外基质蛋白,参与多种细胞-基质相互作用和细胞信号转导途径,在肿瘤发展中发挥重要作用。对1124种血浆蛋白进行中介分析,结果提示血浆SPARC可能介导了嗜酸性粒细胞对胃癌的保护作用(Beta=-0.030,95%CI:-0.072~0.000,P=0.024)。结论孟德尔随机化分析证明嗜酸性粒细胞计数是降低胃癌发病率的独立因素,血浆SPARC在此过程中起中介作用,外周嗜酸性粒细胞计数和外周血SPARC有潜力成为胃癌发生的早期临床指标和治疗靶点,孟德尔随机化的方法还有效地避免了反向因果关系和社会心理等因素造成的偏倚,但是未来仍需要更多的研究来证明其内部的生物学机制。展开更多
文摘In this work, lateral deformation of human eosinophil cell during the lateral indentation by an optically trapped microbead of diameter 4.5 µm is studied. The images were captured using a CCD camera and the Boltzmann statistics method was used for force calibration. Using the Hertz model, we calculated and compared the elastic moduli resulting from the lateral force, showing that the differences are important and the force should be considered. Besides the lateral component, the setup also allows us to examine the lateral cell-bead interaction. The mean values of the properties obtained, in particular the elastic stiffness and the shear stiffness, were Eh = (37.76 ± 2.85) µN/m and Gh = (12.57 ± 0.32) µN/m. These results show that the lateral indentation can therefore be used as a routine method for cell study, because it enabled us to manipulate the cell without contact with the laser.
文摘BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.
文摘There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.
基金supported by grants from the National Natural Science Foundation of China (No.81170021 and No.30900647)
文摘Summary： In order to study whether cysteine-rich 61 protein （cyr61） is involved in the pathogenesis of asthma and its relation to airway inflammation, the effect of dexamethasone （Dxm） on the expression of cyr61 in the lung tissues of asthmatic mice was investigated. Forty BALB/c mice were divided into asthma group （n=15）, control group （n=10） and Dxm group （n=15）. The asthma group was sensitized and challenged by ovalbumin （OVA）. The mice in Dxm group were intraperitoneally administered with Dxm after OVA challenge. The expression of cyr61 in the lung tissues was detected by using immuno- histochemistry, and that of eotaxin protein in the bronchoalveolar lavage fluid （BALF） by using en- zyme-linked immunosorbent assay （ELISA）. The number of inflammatory cells in BALF was also ana- lyzed. The results showed that the cyr61 expression was highest in asthma group （P〈0.05）, followed by Dxm group （P〈0.05） and control group. The cyr61 had a positive correlation with the total nucleated cells （r=0.867, P〈0.05）, especially eosinophils （r=0.856, P〈0.05）, and eotaxin level （r=0.983, P〈0.05） in the BALF. Our findings suggested that cyr61 is expressed in airway epithelial cells and has a positive correlation with eotaxin and number of airway infiltrating eosinophils.
文摘Langerhans cell histiocytosis(LCH) is a rare condition mostly seen in children and adolescents. Eosinophilic granuloma(EG) is one of its three clinical entities and is considered as a benign osteolytic lesion. Many reports of patients with spine histiocytosis are well documented in the literature but it is not the case of atlantoaxial localization. We report here a new observation of atlantoaxial LCH in a 4-year-old boy revealed by persistent torticollis. He was successfully treated with systemic chemotherapy and surgery. Inter-body fusion packed by autologous iliac bone was performed with resolution of his symptoms. It is known that conservative treatment is usually sufficient and surgery should be reserved for major neurologic defects in spine EG. In atlantoaxial lesion, surgical treatment should be frequently considered.
文摘Background:Nuclear factor kappa B(NF-kappa B) overactivation plays a crucial role in T-helper 2 (Th2)-biased allergic airway inflammation by increased activation and decreased apoptosis of CD4(+) T cells. We have shown that targeted NF-kappa B suppression in dendritic cells by adenoviral gene transfer of a novel mutated inhibitor of NF-kappa B(I kappa B alpha) (AdI kappa B alpha M) contributes to T-cell tolerance, but the immunosuppressive action of AdI kappa B alpha M on memory(CD45RO(+)) CD4(+) T cells remains enigmatic. Methods:CD45RO(+) T cells from Dermatophagoides farinaei-sensitized asthmatic patients, untransfected or transfected with AdI kappa B alpha M or AdLacZ(beta-galactosidase) for 24 h, were stimulated with anti-CD3(1.0 mu g/ml) plus anti-CD28(0.5 mu g/ml) monoclonal antibody for an additional 24 h. I kappa B alpha M transgene expression and NF-kappa B activation were detected by polymerase chain reaction(PCR), reverse transcription-PCR(RT-PCR), Western blot analysis, and electrophoretic mobility shift assay. Phenotype and apoptosis were measured by flow cytometry, annexin V binding, and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling analyses. Cytokine production and cell proliferation were determined using enzyme-linked immunosorbent assay andH-3 thymidine incorporation. Results:A unique 801-bp I kappa B alpha M cDNA and a dose-dependent increase in I kappa B alpha M transgene expression were observed in AdI kappa B alpha M-transfected CD45RO(+) T cells. Significantly, AdI kappa B alpha M inhibited CD3/CD28-mediated NF-kappa B activation in CD45RO(+) T cells, leading to evident apoptosis, reduction of eotaxin, RANTES, Th1 interferon (IFN)-gamma and interleukin (IL)-2, and Th2 (IL-4, IL-5, and IL-13 despite a slight decrease in IL-10) cytokines and secondary proliferative response. AdI kappa B alpha M also upregulated cytotoxic T lymphocyte-associated antigen 4(CTLA-4) and downregulated CD69 besides no change in CD28. Conclusion:I kappa B alpha M might be beneficial to augment memory CD4(+) T-cell tolerance through modulating B7-CD28/CTLA-4 co-stimulatory pathways and NF-kappa B-dependent cytokine profiles in allergic inflammatory diseases including asthma.
文摘Introduction: Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the proliferation of specialized bone marrow-derived Langerhans cells (LCs) and mature eosinophils, resulting in solitary or few, indolent and chronic, lesions of bone or other organs called eosinophilic granulomas. Calvarial LCH is quite rare and an underappreciated differential etiology of skull lesions. We present a most unusual case of a young child with hyperacutely symptomatic langerhans histiocytosis of the skull. Method: A 7-year-old male presented with a history of increasing (progressive) frontal headaches of 8 days duration, unaccompanied by associated nausea, vomiting, or diplopia. His only additional complaint was a hard bump on his forehead. MRI and CT done in the ER identified a right fronto-parietal lesion with associated skull erosion. Nuclear medicine and SPECT studies confirmed an erosive skull lesion without significant metabolic activity. A right frontal craniectomy and excision was performed. Results: A soft, rubbery well-circumcised mass coming from the diploic layer of the skull with involvement of bone was identified. The mass had eroded both the outer and inner table of the skull, and the involved area of the right frontal bone was resected. Intra-operative histo-pathologic analysis of the lesion revealed Langerhans cell histiocytosis without involvement of the dura. The patient experienced no neurological worsening as a result of the resection. He was discharged home in stable condition. Conclusion: LCH lesions of the skull are common findings, however, this focal hyperacute symptomatic presentation is most rare and should not deter us from anticipating an erosive bony tumor and planning timely surgical management.
文摘目的外周血免疫细胞计数与胃癌的发生发展以及胃癌患者的预后之间的联系往往易受到反向因果关系和混杂因素的影响,研究旨在运用孟德尔随机化分析排除相关偏倚,阐明外周免疫细胞计数和胃癌的因果关系。方法主要采用单因素和多因素孟德尔随机化的方法,利用全基因组关联研究(genomewide association study,GWAS)数据,探究外周血中各免疫细胞亚型与胃癌发生风险之间的因果关系。将白细胞、粒细胞、中性粒细胞、嗜酸性粒细胞、嗜碱性粒细胞、淋巴细胞、单核细胞计数作为暴露因素,选用逆方差加权法作为单变量孟德尔随机化分析的主要方法。随后进行了两步法中介分析,探究血浆蛋白可能起到的作用。结果淋巴细胞(OR=1.094,95%CI:1.009~1.185,P=0.029)、嗜酸性粒细胞(OR=0.881,95%CI:0.813~0.955,P=0.002)与胃癌之间存在因果关系,敏感性分析进一步证实了此结果的可靠性。而嗜酸性粒细胞降低胃癌发生风险之间的关联在多变量孟德尔随机化分析中仍然显著(OR=0.807,95%CI:0.671~0.970,P=0.023),反向因果关系不显著。酸性富含半胱氨酸分泌蛋白(secreted protein acidic and rich in cysteine,SPARC)是一种细胞外基质蛋白,参与多种细胞-基质相互作用和细胞信号转导途径,在肿瘤发展中发挥重要作用。对1124种血浆蛋白进行中介分析,结果提示血浆SPARC可能介导了嗜酸性粒细胞对胃癌的保护作用(Beta=-0.030,95%CI:-0.072~0.000,P=0.024)。结论孟德尔随机化分析证明嗜酸性粒细胞计数是降低胃癌发病率的独立因素,血浆SPARC在此过程中起中介作用,外周嗜酸性粒细胞计数和外周血SPARC有潜力成为胃癌发生的早期临床指标和治疗靶点,孟德尔随机化的方法还有效地避免了反向因果关系和社会心理等因素造成的偏倚,但是未来仍需要更多的研究来证明其内部的生物学机制。
