Modeling Noisy Annotations for Point-Wise Supervision.

Point-wise supervision is widely adopted in computer vision tasks such as crowd counting and human pose estimation. In practice, the noise in point annotations may affect the performance and robustness of algorithm significantly. In this paper, we investigate the effect of annotation noise in point-wise supervision and propose a series of robust loss functions for different tasks. In particular, the point annotation noise includes spatial-shift noise, missing-point noise, and duplicate-point noise. The spatial-shift noise is the most common one, and exists in crowd counting, pose estimation, visual tracking, etc, while the missing-point and duplicate-point noises usually appear in dense annotations, such as crowd counting. In this paper, we first consider the shift noise by modeling the real locations as random variables and the annotated points as noisy observations. The probability density function of the intermediate representation (a smooth heat map generated from dot annotations) is derived and the negative log likelihood is used as the loss function to naturally model the shift uncertainty in the intermediate representation. The missing and duplicate noise are further modeled by an empirical way with the assumption that the noise appears at high density region with a high probability. We apply the method to crowd counting, human pose estimation and visual tracking, propose robust loss functions for those tasks, and achieve superior performance and robustness on widely used datasets.

Uncovering the potential functions of lymph node metastasis-associated aberrant methylation differentially expressed genes and their association with the immune infiltration and prognosis in bladder urothelial carcinoma.

Background: Bladder urothelial carcinoma (BLCA) is a malignant tumor of the urinary system. This study aimed to explore the potential role of lymph node metastasis-associated aberrant methylation differentially expressed genes (DEGs) in BLCA. Methods: CHAMP and limma packages were used to identify lymph node metastasis-associated aberrant methylation DEGs. Univariate Cox analysis and Lasso analysis were performed to identify the signature genes, and multivariate Cox analysis was used to construct the risk score. Subsequently, the molecular characteristics of the signature genes and the relationship between risk score and prognosis, clinical characteristics and immune cell infiltration were analyzed. The signature gene AKAP7 was selected for functional verification. Results: A novel risk score model was constructed based on 12 signature genes. The risk score had a good ability to predict overall survival (OS). The nomogram constructed based on age, N stage and risk score had a higher value in predicting the prognosis of patients. It was also found that stromal activation in TIME may inhibit the antitumor effects of immune cells. Functional enrichment analysis revealed that ECM receptor interaction and focal adhesion were two important pathways involved in the regulation of BLCA. Immunohistochemistry showed that AKAP7 may be associated with the occurrence, clinical stages and grades, and lymph node metastasis of BLCA. In vitro cell experiments showed that the migration and invasion ability of EJ cells was significantly inhibited after AKAP7 overexpression, while the migration and invasion ability of T24 cells was significantly promoted after AKAP7 knockdown. Conclusion: The risk score model based on lymph node metastasis-associated aberrant methylation DEGs has a good ability to predict OS and is an independent prognostic factor for BLCA. It was also found that stromal activation in TIME may inhibit the antitumor effects of immune cells. This implicates aberrant methylation modifications as an important factor contributing to the heterogeneity and complexity of individual tumor microenvironments. Functional enrichment analysis revealed that ECM receptor interaction and focal adhesion were two important pathways involved in the regulation of BLCA, which contributed to the exploration of the pathological mechanism of BLCA. In addition, immunohistochemistry showed that AKAP7 may be associated with the occurrence, progression and lymph node metastasis of BLCA. In vitro cell experiments showed that AKAP7 could also inhibit the migration and invasion of cancer cells.

Selenium Application Enhances the Accumulation of Flavones and Anthocyanins in Bread Wheat (Triticum aestivum L.) Grains.

Selenium (Se) biofortification in wheat reduces the risk of Se deficiency in humans. Se biofortification increases the concentration of Se and anthocyanins in wheat grains. However, it is unknown whether Se biofortification can enhance flavonoids other than anthocyanins and the mechanism underlying flavonoid accumulation in wheat grains. Here, foliar application of selenite solution in wheat was conducted 10 days after flowering. Metabolite profiling and transcriptome sequencing were performed in Se-treated grains. A significant increase in the total contents of Se, anthocyanins, and flavonoids was observed in Se-treated mature grains. Twenty-seven significantly increased flavonoids were identified in Se-treated immature grains. The significant accumulation of flavones (tricin, tricin derivatives, and chrysoeriol derivatives) was detected, and six anthocyanins, dihydroquercetin (the precursor for anthocyanin biosynthesis) and catechins were also increased. Integrated analysis of metabolites and transcriptome revealed that Se application enhanced the biosynthesis of flavones, dihydroquercetin, anthocyanins, and catechins by increasing the expression levels of seven key structural genes in flavonoid biosynthesis (two TaF3Hs, two TaDFRs, one TaF3'5'H, one TaOMT, and one TaANR). Our findings shed new light on the molecular mechanism underlying the enhancement in flavonoid accumulation by Se supplementation and pave the way for further enhancing the nutritional value of wheat grains.

Patients with IBD have a more cautious attitude towards COVID-19 vaccination.

Background: To understand the awareness of COVID-19 vaccine, the willingness to vaccinate and the influencing factors of willingness to vaccinate in inflammatory bowel disease (IBD) patients. Methods: The online questionnaire was distributed to conduct a survey to analyze and evaluate the willingness, awareness and trust in vaccines of IBD patients. Bivariate analyses and logistic regression models were used to analysis influencing factors. Results: We sent the questionnaire to the WeChat group for patient management and 304 patients responded, out of which 16 respondents had to be excluded and 288 respondents were included for the analysis. Among them, 209 patients vaccinated with COVID-19 vaccine. Among the non-vaccinated 79 patients, the main reasons for their concerns were afraid of vaccination aggravating IBD and fear of adverse effects. Our results showed that IBD patients with long disease duration were more willing to receive COVID-19 vaccination (P<0.05). We also observed that a high perception of benefits and cues to action to receive the vaccine were the two most important constructs affecting a definite intention for COVID-19 vaccination (P<0.05). Conclusions: Patients with IBD have a more cautious attitude towards COVID-19 vaccination, which may lead to a higher rate of vaccine hesitancy. Further efforts should be made to protect patients with IBD from COVID-19 infections and achieve adequate vaccination coverage.

SO2-Tolerant Catalytic Removal of Soot Particles over 3D Ordered Macroporous Al2O3-Supported Binary Pt-Co Oxide Catalysts.

The catalytic purification of soot particles is dependent on the SO2 tolerance and activity of the catalysts in practical application. Herein, we have elaborately fabricated the nanocatalysts of three-dimensionally ordered macroporous (3DOM) Al2O3-supported binary Pt-cobalt oxide nanoparticles (NPs) using the method of gas bubbling-assisted membrane precipitation (GBMP), abbreviated as Pt-CoOx/3DOM-Al2O3. Three-dimensionally ordered macroporous Al2O3 support can not only improve the contact performance between the soot and active sites but also possess surface acidity to improve the SO2 tolerance. Supported binary Pt-CoOx NPs over 3DOM-Al2O3 have high-efficient properties for activating NO and O2. The Pt-CoOx/3DOM-Al2O3 catalyst exhibits super catalytic performance and SO2 tolerance during the removal of soot particles, whose values of turnover frequency (TOF) and T50 are 0.29 h-1 and 368 °C, respectively. The catalytic and SO2-tolerant mechanisms of the Pt-CoOx/3DOM-Al2O3 catalyst for soot purification are systematically studied by in situ diffuse reflectance infrared Fourier transform (DRIFT) spectra. The synergistic effect of binary Pt-CoOx NPs plays a vital role in the oxidation of NO to NO2 as a key step during catalytic soot removal, and the surface acidity of 3DOM-Al2O3 can not only inhibit the adsorption of SO2 but also enhance the decomposition of surface hydrosulfate species. This work provides a novel strategy to the development of high-efficient catalysts for SO2-tolerant catalytic removal of soot particles in both fundamental research and practical applications.

An Improved Method for Road Extraction from High-Resolution Remote-Sensing Images that Enhances Boundary Information.

At present, deep-learning methods have been widely used in road extraction from remote-sensing images and have effectively improved the accuracy of road extraction. However, these methods are still affected by the loss of spatial features and the lack of global context information. To solve these problems, we propose a new network for road extraction, the coord-dense-global (CDG) model, built on three parts: a coordconv module by putting coordinate information into feature maps aimed at reducing the loss of spatial information and strengthening road boundaries, an improved dense convolutional network (DenseNet) that could make full use of multiple features through own dense blocks, and a global attention module designed to highlight high-level information and improve category classification by using pooling operation to introduce global information. When tested on a complex road dataset from Massachusetts, USA, CDG achieved clearly superior performance to contemporary networks such as DeepLabV3+, U-net, and D-LinkNet. For example, its mean IoU (intersection of the prediction and ground truth regions over their union) and mean F1 score (evaluation metric for the harmonic mean of the precision and recall metrics) were 61.90% and 76.10%, respectively, which were 1.19% and 0.95% higher than the results of D-LinkNet (the winner of a road-extraction contest). In addition, CDG was also superior to the other three models in solving the problem of tree occlusion. Finally, in universality research with the Gaofen-2 satellite dataset, the CDG model also performed well at extracting the road network in the test maps of Hefei and Tianjin, China.

Efficient synthesis of polysaccharide with high selenium content mediated by imidazole-based acidic ionic liquids.

Exploring new solvents or catalysts has great prospect for the derivatization of poorly soluble natural polysaccharides as bio-resources which were extracted from food or industrial waste residue, as compared to traditional reaction system. In this work, selenized Artemisia sphaerocephala polysaccharide (SePAS) was synthesized by using imidazolium-based acidic ionic liquids (AILs) as catalyst. The results showed the highest Se content increased to 20438 µg/g compared to conventional method (1703 µg/g), indicating AILs could enhance selenylation reactivity and Se content was controlled by the acidity due to the protonation effect of H2SeO3 by AILs. FT-IR, X-ray photo-electron spectroscopy (XPS) and 13C NMR results exhibited that seleno-group exists in SePAS and the substitution position was at C-6. The hydrogen bonding effect and acidity of AILs showed regulation on weight average molecular mass of SePAS. Therefore, AILs with excellent catalytic efficiency could be as potential catalyst for full use of polysaccharide-rich resources.

Disease-related information requirements in patients with Crohn's disease.

AIM: To explore the demands for different disease-related information and the acceptance of various information sources in patients with Crohn's disease (CD). METHODS: This study included 159 patients with CD and was conducted from April 2017 to December 2017 in our hospital. We obtained the demographic characteristics of the patients and used the modified information demands questionnaire to assess patients' disease information demands, covering 4 aspects which include general knowledge, fertility, clinical treatment, and daily management. Then, we analyzed the factors associated with the information demand. In addition, we studied the patients' acceptance of different information sources. RESULTS: The disease-related information demands of patients with CD are generally high. Female patients, young patients, and patients with plans to have children have significantly higher information demands concerning fertility. The information demands in clinical treatment are higher in young patients. Patients living in the countryside and patients with a short disease duration have high information demands concerning life management. The patients' acceptance of different information sources is variable. Doctor-mediated guidance, brochures, and videos are the top 3 patient choices for information sources. CONCLUSION: Patients' information demands concerning many aspects of CD are generally high. Certain demands are significantly associated with the demographic characteristics of the patients. Doctor-mediated guidance, brochures, and videos are the top 3 patient choices for information sources. Therefore, corresponding education programs can be developed to improve the physical and psychological health of CD patients in the future.

Prognostic Analysis of Duodenal Gastrointestinal Stromal Tumors.

AIM: This study aims to analyze factors possibly related to the prognosis of duodenal gastrointestinal stromal tumors (DGISTs). METHODS: We collected and retrospectively analyzed clinical and pathological data of 62 patients with primary DGISTs. All the patients were hospitalized and received complete surgical resection at Shanghai Ruijin Hospital from September 2003 to April 2015. We followed up the patients to determine survival outcomes. We also analyzed the effect of clinical and pathological factors on disease-free survival (DFS) and overall survival (OS) of the patients. RESULTS: Kaplan-Meier univariate survival analysis demonstrated that tumor size, mitotic index, Ki-67 index, and pathological risk were correlated with the DFS and OS of the patients (DFS P = 0.039, 0.001, <0.001, and 0.005, resp.; OS P = 0.027, 0.007, <0.001, and 0.012, resp.). Cox multivariate regression analysis revealed that Ki-67 index was an independent prognostic factor affecting DFS and OS (P = 0.007 and 0.028, resp.). Moreover, Kaplan-Meier survival analysis showed that imatinib treatment for patients with recurrence was correlated with prolonged OS (P = 0.002). CONCLUSION: Prognosis for DGIST treated by R0 resection is favorable. High level of Ki-67 can be an independent risk factor of DGIST prognosis. Adjuvant imatinib therapy for patients with tumor recurrence could probably lead to prolonged survival.

Synthesis and structural features of phosphorylated Artemisia sphaerocephala polysaccharide.

Phosphorylation is a key route to achieve varieties of biological activities for polysaccharides. Currently, conventional phosphorylation reagents are characterized by long processing times and high reaction temperatures. Here, we reported phosphorylation of Artemisia sphaerocephala polysaccharides (PASP) with the degrees of substitution (DS) of 0.34-0.54 in mild reaction conditions (3-4h and 25°C) by employing POCl3/pyridine technique. FT-IR spectroscopy and X-ray photoelectron spectroscopy (XPS) analysis confirmed the appearance of phosphate ester (P5+) groups in PASP. Size exclusion chromatography combined with multi-angle laser light scattering (SEC-MALLS) result clearly showed temperature-dependent increment of weight average molecular mass (MW). High temperature facilitated the reaction of phosphoryl chloride with primary and secondary hydroxyl groups, favoring the crosslinking of polysaccharide chains by phosphate di-esters as further confirmed in 13C NMR determination. Our results provide insight into the relationship between the structure and reaction conditions of phosphorylated polysaccharide, which is important for understanding and exploiting these derivatives in a wide range of applications.

Comparison of patients' tolerance between computed tomography enterography and double-balloon enteroscopy.

BACKGROUND: Computed tomography enterography (CTE) and double-balloon enteroscopy (DBE) are widely used in diagnosis of small bowel diseases. Both of these examinations bring discomfort to patients. The aim of this study was to compare patients' tolerance and preference between CTE and DBE. METHODS: From August 1, 2014 to December 31, 2016, patients with suspected or known small bowel diseases who underwent both CTE and DBE were prospectively enrolled in our study. They were asked to fill out a questionnaire evaluating discomfort of the procedure after each examination. RESULTS: One hundred and seven patients completed our study. Abdominal distension, painfulness, tenesmus, general discomfort, prolonged duration, difficulty in completing the test, and discomfort after the examination were significantly lower with CTE than with DBE (P<0.001, respectively). Mannitol intake (47.7%), bowel preparation (31.9%), and radiation exposure (15.0%) were regarded as the three most intolerable burdens in CTE. Painfulness (38.3%), bowel preparation (26.2%), and invasiveness (16.8%) were considered as the three most unacceptable parts of DBE. More patients (61.7%) preferred to repeat CTE rather than DBE (P<0.001). CONCLUSION: Compared to DBE, CTE was a more tolerable and less burdensome examination and enjoyed higher preference by most patients.

The immune injury effects and clinical significance of eosinophils in auto-immune-related hematocytopenia.

Eosinophils (EOS) quantity, active state, peroxidase activity (POX), and HLA-DR expression in bone marrow of 176 Auto-Immune-Related Hematocytopenia (AIRH) patients were analyzed. Immunofluorescent staining (IF) is performed to observe the expression of immunizing molecules on EOS. In serum of AIRH patients the levels of IL-4, IL-5, IL-6, IL-12, IL-17, and IFN- γ were increased but there was no significance on IL-2 level. In marrow of AIRH, activated EOS expressed POX, and other molecules, it played various cell-mediated immunity injury roles to hemocyte. EOS might be possessed with multiple immunological fuctions, it playes an important immune effect in AIRH autoimmune pathological processes.

[Immune mechanism and clinical significance of infection immunity activation for medullary hematopoietic injury of immune-related hematocytopenia syndrome].

OBJECTIVE: To observe the pathologic effects of marrow hematopoietic cell with immunologic injury induced by infection immunity activation in patients with immune related hematocytopenia syndrome (IRHS) and elucidate its immunologic mechanism and clinical significance. METHODS: A total of 276 IRHS patients with acute and chronic infections were recruited from 2008 to 2013. ELISA was used to detect the levels of interleukin-6 (IL-6), IL-12, IL-17 and interferon gamma (IFN-γ) in peripheral blood sera of IRHS patients before and after therapy. Flow cytometry was performed to detect the proportion of lymphocyte subgroups in peripheral blood. Immunochemical staining was used to analyze the expressive states of peroxydase (POX), HLA-DR in bone marrow and non-specific esterase. The expressive states of CD4, CD8, CD56, IFN-γ, porforin, granzyme, FcγRII, anti-human IgG, mannose receptor (MR), IL-12 and IL-17A in bone marrow cells and hematopoietic microenvironment were analyzed with immunofluorescence (IF). According to the above immunological indices, antibiotics were prescribed along with medaron and ciclosporin A (CsA). RESULTS: Among 276 patients, the levels of IL-6, IL-12, IL-17 and IFN-γ were higher than those in control group (all P < 0.05) . After treatment, the cytokine levels above decreased to normal gradually. The levels of CD3(+) CD4(+) T and NK cells increased respectively in those with concurrent viral or mycoplasma infection(54.23% ± 3.07% and 50.11% ± 3.09% vs 35.25% ± 5.16%, 22.71% ± 2.26% and 19.49% ± 2.07% vs 14.91% ± 4.87%) . The proportions of CD3(+) CD4(+) T and CD19(+) B cells increased in sera of patients with bacterial infection (40.22% ± 4.31% vs 35.25% ± 5.16%, 29.01% ± 4.32% vs 11.56% ± 2.54%) . But the proportion of CD3(+) CD8(+) T cells increased in patients with viral infection of type B hepatitis(32.51% ± 3.44% vs 25.08% ± 4.43%) (all P < 0.05). In patient marrow samples, dendritic cell, T lymphocyte, eosinophilic granulocyte and macrophage were activated to express many above mentioned immunological molecules. Both the destructive pattern of hemocyte and the degree of pathological lesion induced by these immunocytes were related with the cause of infection immunity activation and morbid state of patients. After individualized treatment, 264 patients showed elevated hemogram at 4-8 weeks while the relapse of 12 patients persisted until an initiation of cytotoxic drug and a gradual restoration of hemogram. CONCLUSIONS: Infection is one of the most important factors of IRHS. Excessive activation of infection immunity may induce the disorder of immune system. Then immunocytes destroy or damage those hemocytes with pathological changes through different immunological pathways. The pathogenetic condition and outcome is related with infected pathogen and intrasubject immune state. Control of pathogenic microorganism infection and glucocorticoid treatment may suppress the excessive activation of immunocytes so as to become important preventive and curing measures of IRHS.

Mechanisms of immune injury and heterogeneity of bone marrow hematopoietic cells island in patients with auto-immuno-related hematocytopenia.

Because of environmental pollution more and more people are suffered with auto-immuno-related hematocytopenia (AIRH). Serum IL-12, IL-17, and IFN-γ levels were detected by ELISA and lymphocyte subsets were analyzed by flow cytometry. Peroxidase (POX) and HLA-DR of immune cells were detected by cytochemical and immunochemical staining. Cells expressing anti-human IgG, FcγR II, MR, and other molecules in HI were detected by immunofluorescence. Serum IL-12, IL-17, and IFN-γ levels of patients were significantly higher than control group. Lymphocyte subsets of patients showed that the percentages of CD19+ B cells and CD3+ CD8+ T cell in peripheral blood were both significantly elevated. HI were mainly classified into three types, in these three types of hematopoietic cells island, peroxidase, and HLA-DR expression varied. Hematopoietic cells with pathological changes expressed anti-human IgG. The immunocytes with different levels of immunomolecules adhered captured and devoured abnormal hematopoietic cells. Immune cells expressed IL-12, IL-17A, and IL-17RA, leading to inflammatory injury of hematopoietic cells. HI destroys cells which connect auto-antibodies. Immune cells in HI express a variety of immune molecules, promote cell immune responses, and amplify the inflammatory reaction by ADCC effect or phagocytosis. These ultimately destruct directly and damage indirectly hematopoietic cells.

Immune mechanism and clinical significance of macrophage to medullary hematopoietic injury of immune-related hematocytopenia patients.

BACKGROUND: Immune-related hematocytopenia (IRH) is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage (Mφ) in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Mφ in hematopoietic cell injury. METHODS: ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-γ levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase (POX), nonspecific esterase (NSE), hemosiderin granules, and HLA-DR activity of Mφ in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Mφ membrane FcγIIreceptor (FcγIIR), mannitose receptor (MR), IFN-γ, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC) hematopoietic cell islands (HI) in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Mφ bloodthirsty phenomenon; if necessary, association of Cyclosporine A (CsA) should be used and chalybeate should be supplemented. RESULTS: In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-γ were increased. After treatment, the cytokine levels gradually became normal. The activated Mφ in the marrow highly expressed NSE and POX, and Mφ swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Mφ expressed HLA-DR, MR, ICAM-1, IFN-γ, and IL-12. For patients with humoral immunity activation and bacterial infection, Mφ weakly expressed IL-17A but highly expressed FcγIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count (WBC) significantly reduced, Mφ weakly expressed FcγIIR, secretory highly expressed IL-17A, and the phenomena that Mφ adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Mφ occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve. CONCLUSIONS: Mφ is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Mφ, upregulate the impression of immune molecule and receptors, form ADCC HI, aggravate hematopoietic injury, and accelerate the destruction on hematopoietic cell.

[The immunological effect of anti-leukemic tumor induced by eosinophilic granulocyte].

OBJECTIVE: To investigate the biological effect of anti-leukemic cells induced by eosinophilic granulocyte (EOS) in bone marrow of patients with chronic myelogenous leukemia (CML). METHODS: The BCR-ABL fusion gene as well as the expression of IL-12 and IL-17 mRNA were performed by RT-PCR. The serum concentrations of cytokine IL-12 and IL-17 were determined by enzyme-linked immuno sorbent assay (ELISA). Immunochemistry staining and cytochemistry staining were used to observe the peroxidase (POX) and human leukocyte antigen (HLA)-DR expression of EOS in bone marrow. Immunofluorescence staining was used to observe mannose receptor (MR), IL-12, IL-17A and IL-17 receptor A (IL-17RA) expression of EOS. The results between the CML patients and the healthy controls were compared. RESULT: Serum levels of IL-12 and IL-17 were higher in the 60 CML patients [(196.33 ± 21.79) ng/L and (36.55 ± 3.01) ng/L] than those in the controls [(96.60 ± 4.92) ng/L and (23.74 ± 1.36) ng/L]. In the 32 patients with activated EOS, the levels of IL-12 and IL-17 were (273.12 ± 17.16) ng/L and (40.11 ± 6.13) ng/L, which were significantly higher than those in the non-activated EOS [(126.16 ± 14.27) ng/L and (28.14 ± 5.29) ng/L] (P values < 0.01). IL-12 and IL-17 mRNA were expressed in activated EOS, while BCR-ABL fusion gene was not found. The amounts of EOS were increased abnormally in the bone marrow and peripheral blood of the CML patients with POX positive staining in the cytoplasm and weakly positive HLA-DR staining. It was observed easily by a microscope that EOS could attack leukemic cells in bone marrow through adhesion, capture and phagocytosis. Activated EOS could express IL-12, IL-17A and MR, which was related with the serum levels of these cytokines. CONCLUSIONS: Activated EOS in bone marrow of CML patients could express IL-12 and IL-17. Activated EOS could induce coup injury to leukemic cell by releasing POX and expressing IL-12 and IL-17. It can also capture or swallow target cells via the expression of MR on the membrane. EOS may play an important role in the anti-tumor immunologic function in bone marrow of CML patients.

[Pathological effects and clinical significance of eosinophils in autoimmune-related hematocytopenia].

OBJECTIVE: To observe the pathological effects induced by eosinophils (EOS) in the process of cellular damage in immune-related hematocytopenia (IRH) and elucidate the immunologic mechanism and clinical significance of EOS. METHODS: Enzyme-linked immunosorbent assay (ELISA) was performed to determine the serum concentrations of interleukins (IL)-2, IL-4, IL-5, IL-6, IL-12 and IL-17 in 117 IRH patients from February 2008 to February 2012 in our hospital. Their quantity, activity, peroxidase (POX) and HLA-DR expression of EOS were observed and analyzed. Immunofluorescent staining was used for detecting anti-human immunoglobulin (IgG) on the surface of hematopoietic cell and the expressions of intercellular adhesion molecule-1 (ICAM-1), Fcγ receptor II (FcγRII), mannose receptor (MR), IL-5 receptor (IL-5R), IL-12, IL-12 receptor (IL-12R), IL-17A and IL-17 A receptor (IL-17RA) on EOS. TdR incorporation method was employed to determine the capability of antigen presentation and IL-17 mRNA expression examined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The serum levels of IL-4, IL-5, IL-6, IL-12 and IL-17 were (170.9 ± 14.7), (112.9 ± 8.2), (131.8 ± 13.8), (339.2 ± 26.1) and (42.5 ± 2.2) ng/L in patient group versus (60.3 ± 11.0), (34.1 ± 2.2), (91.0 ± 12.3), (94.0 ± 3.3) and (20.0 ± 1.1) ng/L in control group respectively. All incremental percentages of IL-5, IL-12 and IL-17 were 100% (117/117) and they were correlated with disease. Diastrophic EOS could be found in marrow of patient with decreased leucocyte with HLA-B27(+). Hematopoietic cells were adhered, captured and phagocytized actively by activated EOS. Activated EOS showed strongly positive POX while POX of neutrophils attacked by EOS became weakened. Activated EOS could express HLA-DR and played a role in antigen presentation. EOS could secrete cytokine IL-17 through a transcription of IL-17 mRNA. And EOS could also express ICAM-1, FcγRII, MR, IL-5R and IL-12, IL-17A, IL-17RA. CONCLUSIONS: Capable of expressing or secreting various cytokines and molecules, EOS have immunological functions of adhering, capturing and phagocytizing pathological hemocytes. It also participates in pathogenic process of IRH. Thus EOS is probably an important immune effector cell in the process of in situ marrow damage.

[Clinical significance of telomerase activity detection of myeloid element in immune related hematocytopenia].

OBJECTIVE: To observe the telomerase activity (TA) in bone marrow mononuclear cell (BMMNC) at pre-therapy and post-therapy in patients with immune related hematocytopenia and immune related pancytopenia (IRH/IRP) so as to explore the relationship between TA and disease process. METHODS: TA in BMMNC of 108 IRH/IRP patients was detected with telomeric repeat amplification protocol (TRAP)-PCR-ELISA. The expressions of anti-human immunoglobulin IgG, FcγII receptor (FcγIIR), mannose receptor (MR) and interleukin 17A (IL-17A) located on membrane surface were observed by immunofluorescence (IF). A total of 30 iron deficiency anemia patients were selected as case control. RESULTS: The TA of 108 IRH/IRP patients were 0.251 ± 0.021. And it increased as compared with the control group of 0.062 ± 0.031 at pre-therapy (P < 0.01). The HLA-B27(+) patients among them was 0.270 ± 0.020 while HLA-B27(-) patients 0.181 ± 0.013 (P < 0.05). And HLA-B27(+)IgG elevated IRP was 0.341 ± 0.016 and HLA-B27(-)IgG elevated 0.183 ± 0.010, the difference of TA was significant between two groups (P < 0.01). IgG antibody positive immature hemocyte could be observed in marrow of IRH/IRP patients, and FcγIIR was expressed highly on those activated macrophage (Mφ) in bone marrow. Both IL-17A and MR were expressed on activated dendritic cells and Mφ in marrow of HLA-B27(+) patients. After the therapy of glucocorticoids associated with cyclosporine A and other drugs, the patient's hemogram recovered and the telomerase in BMMNC were re-devitalized. CONCLUSIONS: The TA of the BMMNC in marrow of IRH/IRP patients is increased, and it shows a close relation between apoptotic degree of hematopoietic cell and the activation of immunocytes. In IRH/IRP, synchronism and equilibrium exist between BMMNC apoptosis and TA.