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1.
Asia Pac J Oncol Nurs ; 11(3): 100368, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38426045

RESUMO

Effectively addressing the challenges posed by relapsed and refractory diffuse large B-cell lymphoma, particularly when employing autologous hematopoietic stem cell transplantation and CAR-T therapy, requires a comprehensive approach to treatment and nursing. This case report emphasizes a nursing strategy focused on managing neurotoxicity post-CAR-T therapy. Nursing interventions include the identification of neurotoxicity symptoms, neuropsychiatric management, careful support during lumbar puncture and intrathecal administration, psychological assistance, and adaptive nutritional guidance. The diligent application of treatment and nursing care resulted in a remarkable recovery for the patient, as evidenced by the alleviation of central facial paralysis, improvement in swallowing function (from Grade 4 to Grade 2), and enhanced vocalization. Consistent and specialized nursing care is paramount for effectively managing complications, especially neurotoxicity, in patients undergoing CAR-T therapy. A thorough monitoring of symptoms and personalized care contribute to optimizing treatment outcomes and ensuring patient safety.

3.
Br J Haematol ; 204(4): 1219-1226, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38180132

RESUMO

Venetoclax (VEN) in combination with hypomethylating agents (HMAs) is considered the standard of treatment for individuals with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. We conducted a retrospective analysis that encompassed 16 critically ill patients newly diagnosed with AML who were admitted to the intensive care unit (ICU) and received the VEN and HMA regimen. Among them, 13 were primary AML, and three were MDS-transformed AML. The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 18.9, and the mean sepsis-related organ failure assessment score (SOFA) was 6.2. The average length of the ICU stay was 27.3 days. The median duration of VEN administration was 16 days. After the first course of VEN + HMA, 12 cases (75%) achieved complete remission (CR) or CR with incomplete haematological recovery (CRi). Among the five patients harbouring TP53 mutations, the overall response rate (ORR) was 90%. All patients experienced grade 3-4 haematological adverse events (AEs). With a median follow-up of 9.5 months (range: 0.5-23), the overall survival (OS) rate was 43.75%. TP53-wild patients and CR state after the first course of VEN-HMA indicated better survival. The combination of VEN and HMA has demonstrated a significantly elevated therapeutic response rate in newly diagnosed AML patients with critical illness.


Assuntos
Estado Terminal , Leucemia Mieloide Aguda , Sulfonamidas , Humanos , Estudos Retrospectivos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Leucemia Mieloide Aguda/genética , Resposta Patológica Completa , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
5.
Nat Commun ; 14(1): 3642, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37339964

RESUMO

BCMA-targeting chimeric antigen receptor (CAR) T cell therapy demonstrates impressive clinical response in multiple myeloma (MM). However, some patients with BCMA-deficient tumours cannot benefit from this therapy, and others can experience BCMA antigen loss leading to relapse, thus necessitating the identification of additional CAR-T targets. Here, we show that FcRH5 is expressed on multiple myeloma cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells elicited antigen-specific activation, cytokine secretion and cytotoxicity against MM cells. Moreover, FcRH5 CAR-T cells exhibited robust tumoricidal efficacy in murine xenograft models, including one deficient in BCMA expression. We also show that different forms of soluble FcRH5 can interfere with the efficacy of FcRH5 CAR-T cells. Lastly, FcRH5/BCMA-bispecific CAR-T cells efficiently recognized MM cells expressing FcRH5 and/or BCMA and displayed improved efficacy, compared with mono-specific CAR-T cells in vivo. These findings suggest that targeting FcRH5 with CAR-T cells may represent a promising therapeutic avenue for MM.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Mieloma Múltiplo/patologia , Antígeno de Maturação de Linfócitos B , Xenoenxertos , Recidiva Local de Neoplasia/metabolismo , Linfócitos T
6.
ACS Omega ; 8(9): 8846-8864, 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36910932

RESUMO

In petroleum drilling, carbonate formations characterized by natural fractures can result in troublesome gas-liquid gravity displacement, which refers to the phenomenon that the drilling mud leakage and gas kick are simultaneously triggered. This work focuses on clarifying the mechanism of gas-liquid displacement in vertical fractures during the drilling of carbonate formations and investigating the characteristics of gas-liquid displacement under various conditions. First, the bottom hole pressure allowing for gas-liquid gravity displacement is analyzed, which determines the coexistence condition of leakage and kick in vertical fractures. Then, a theoretical model of gas-liquid displacement flow in a vertical fracture is established. To verify the reliability and accuracy of the model, the results of numerical simulation are compared with those of a visualization experiment. The development process and flow characteristics of gas-liquid displacement in the fracture under different conditions are numerically simulated. The effects of pressure difference, drilling mud property, and fracture geometry on the gas-liquid displacement rate are analyzed. It is found that the drilling mud leakage rate increases with the increase of fracture width, fracture height, and drilling mud density, while it decreases with the increase of pressure difference and fracture length. The gas invasion rate increases with the increase of fracture width, fracture height, and pressure difference, while it decreases with the increase of drilling mud density and fracture length. The equations for leakage rate and gas invasion rate are derived by the response surface method, and the methods for mitigating gas-liquid gravity displacement are discussed. It is expected that the present work provides a better understanding of the gas-liquid gravity displacement in carbonate formations.

7.
Front Immunol ; 13: 904693, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784355

RESUMO

Natural killer (NK) cells have been demonstrated as a promising cellular therapy as they exert potent anti-tumor immune responses. However, applications of NK cells to tumor immunotherapy, especially in the treatment of advanced hematopoietic and solid malignancies, are still limited due to the compromised survival and short persistence of the transferred NK cells in vivo. Here, we observed that fucosyltransferase (FUT) 7 and 8 were highly expressed on NK cells, and the expression of CLA was positively correlated with the accumulation of NK cells in clinical B cell lymphoma development. Via enzyme-mediated ex vivo cell-surface fucosylation, the cytolytic effect of NK cells against B cell lymphoma was significantly augmented. Fucosylation also promoted NK cell accumulation in B cell lymphoma-targeted tissues by enhancing their binding to E-selectin. Moreover, fucosylation of NK cells also facilitated stronger T cell anti-tumor immune responses. These findings suggest that ex vivo fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.


Assuntos
Linfoma de Células B , Neoplasias , Humanos , Imunoterapia , Células Matadoras Naturais , Ativação Linfocitária , Linfoma de Células B/metabolismo , Linfoma de Células B/terapia
8.
J Clin Lab Anal ; 36(7): e24547, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35689538

RESUMO

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is becoming a curable disease with the introduction of therapeutic plasma exchange (TPE). However, cardiovascular complications remain essential causes of mortality in patients with refractory TTP, while the association of cardiac biomarkers with the prognosis of TTP warrants further investigation. METHODS: Patients admitted to the First Affiliated Hospital of Soochow University for refractory TTP from 2013 through 2020 were included in this retrospective study. Clinical characteristics were collected from electronic health records. Biomarker levels on admission and post TPE were recorded. Logistic regression was adopted to identify risk factors for mortality. RESULTS: A total of 78 patients with refractory TTP were included in this study. Twenty-one patients died during hospitalization, with a mortality rate of 26.9%. High-sensitivity cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ratios (AAR) were increased in deceased patients compared with the survival group. Multivariate analysis showed that AAR after TPE was associated with overall mortality (OR: 4.45, 95% CI 1.09-18.19). The areas under the receiver operator characteristic curve (AUC) of AAR, hs-cTnT, and NT-proBNP for the association with mortality were 0.814, 0.840, and 0.829, respectively. CONCLUSION: Higher post-TPE cardiac biomarker levels are associated with increased in-hospital mortality in patients with refractory TTP.


Assuntos
Peptídeo Natriurético Encefálico , Púrpura Trombocitopênica Trombótica , Biomarcadores , China/epidemiologia , Humanos , Fragmentos de Peptídeos , Prognóstico , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/terapia , Estudos Retrospectivos , Troponina T
9.
Oncol Rep ; 47(4)2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35103292

RESUMO

Chidamide, a selective histone deacetylase inhibitor, has antitumour effects. 5­azacitidine (5­AZA), a hypomethylating agent, is effective in treating acute myeloid leukaemia (AML) and myelodysplastic syndrome. However, to the best of our knowledge, the effect of chidamide and 5­AZA on AML cell lines has not been fully investigated. In the present study, the antileukaemia activity of chidamide, alone and in combination with 5­AZA, was assessed on different subtypes of AML cell lines (M1­M5) and primary samples from several patients with AML in vitro. The results indicated that the proliferation of leukaemia cells was significantly and dose­dependently inhibited by chidamide and 5­AZA alone or in combination. The combination also had marked synergistic effects to induce apoptosis of AML cells. The apoptosis of leukaemia cells was induced via downregulation of BCL­2 and myeloid­cell leukemia 1 (MCL­1) levels. Of note, chidamide also degraded the MCL­1 protein in venetoclax­resistant U937 cells, in which the MCL­1 protein is upregulated. In addition, chidamide was able to induce myeloid differentiation (with CD11b upregulation) of AML cell lines or monocytic/dendritic differentiation (with CD86 upregulation) of primary cultured cells from several patients with AML. Chidamide was also able to promote the differentiation of the venetoclax­resistant U937 cell line by upregulating CD11b expression. In conclusion, chidamide alone or combined with 5­AZA may be an effective therapy for AML.


Assuntos
Aminopiridinas/farmacologia , Azacitidina/farmacologia , Benzamidas/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Sinergismo Farmacológico , Epigenômica , Humanos , Células U937 , Regulação para Cima
10.
Front Oncol ; 11: 753712, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778068

RESUMO

BACKGROUND: Among the growing number of patients with hematologic neoplasms hospitalized in the intensive care unit (ICU), the largest proportion of these patients are diagnosed with lymphoma. However, less attention has been paid in the past to identifying critically ill patients and assessing the prognosis of patients in ICU. Traditional critical care-related scores have shown limitations and inaccuracy in predicting mortality risk. METHODS: Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) were searched for in the Marketplace for Information in Intensive Care Medicine III (MIMIC-III) database. We searched mortality within 28 days as the primary endpoint. Logistics regression was used to screen risk factors. A calibration curve was used for internal validation, and the ROC curve and AUC were used to compare the new model with traditional scores. RESULTS: 405 patients with DLBCL are enrolled in the project. Multivariate analysis shows the patients with the level of lactate dehydrogenase (LDH) > 327 U/L had an increased risk of 28-day mortality in ICU than others (OR = 13.04, p<0.01). Notably, length of ICU stay, LDH, creatinine, white blood cell counts, and APS III score are independent prognostic factors for patients with DLBCL in the ICU. Then, all these independent prognostic factors are selected into our prediction model. The new model has good accuracy (C-index=0.863) and a calibration curve, which improves clinical status concerning established ratings such as IPI, NCCN-IPI score, SOFA, APS III, and LODS. The results of a multicenter external validation including 124 DLBCL patients also showed that the new model was more accurate than all other models. CONCLUSIONS: The elevated level of LDH indicates a poor prognosis of patients with DLBCL in the ICU. Our risk score with crossed validation based on the level of LDH shows a significant prognostic value and may be a valuable tool for assessing the critically ill as well.

11.
J Clin Lab Anal ; 35(12): e24100, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34762754

RESUMO

OBJECTIVES: This study aimed to explore clinical indexes for management of severe/critically ill patients with COVID-19, influenza A H7N9, and H1N1 pneumonia by comparing hematological and radiological characteristics. METHODS: Severe/critically ill patients with COVID-19, H7N9, and H1N1 pneumonia were retrospectively enrolled. The demographic data, clinical manifestations, hematological parameters, and radiological characteristics were compared. RESULTS: In this study, 16 cases of COVID-19, 10 cases of H7N9, and 13 cases of H1N1 who met severe/critically ill criteria were included. Compared with COVID-19, H7N9 and H1N1 groups had more chronic diseases (80% and 92.3% vs. 25%, p < 0.05), higher APACHE Ⅱ scores (16.00 ± 8.63 and 15.08 ± 6.24, vs. 5.50 ± 2.58, p < 0.05), higher mortality rates (40% and 46.2% vs. 0%, p < 0.05), significant lymphocytopenia (0.59 ± 0.31 × 109 /L and 0.56 ± 0.35 × 109 /L vs. 0.97 ± 0.33 × 109 /L, p < 0.05), and elevated neutrophil-to-lymphocyte ratio (NLR; 14.67 ± 6.10 and 14.64 ± 10.36 vs. 6.29 ± 3.72, p < 0.05). Compared with the H7N9 group, ground-glass opacity (GGO) on chest CT was common in the COVID-19 group (p = 0.028), while pleural effusion was rare (p = 0.001). CONCLUSIONS: The NLR can be used as a clinical parameter for the predication of risk stratification and outcome in COVID-19 and influenza A pneumonia. Manifestations of pleural effusion or GGO in chest CT may be helpful for the identification of different viral pneumonia.


Assuntos
COVID-19/sangue , COVID-19/diagnóstico por imagem , Influenza Humana/sangue , Influenza Humana/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , COVID-19/etiologia , Doença Crônica , Estado Terminal , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1 , Subtipo H7N9 do Vírus da Influenza A , Influenza Humana/etiologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , Fatores Sexuais
12.
Oncol Rep ; 45(2): 764-775, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416178

RESUMO

Diffuse large B­cell lymphoma (DLBCL) is the most prevalent type of non­Hodgkin's lymphoma with a heterogeneous molecular pathogenesis and aggressive clinical manifestations. The aim of the present study was to investigate the role of miR­196a­3p and its target gene in the development and progression of DLBCL. RT­qPCR was used to detect the miR­196a­3p expression level in human DLBCL cell lines and DLBCL pathological tissues and compare them with the normal control. The clinical significance of the miR­196a­3p expression was also analyzed in DLBCL patients. Next, the effect of miR­196a­3p overexpression on the cell cycle, apoptosis, and proliferation of DLBCL cells was evaluated. To explore its underlying mechanism, the target gene of miR­196a­3p was predicted and validated using bioinformatics and molecular biological approaches. Finally, the expression of this target gene in clinical specimens and its correlation with clinicopathological characteristics were determined. The decreased expression of miR­196a­3p was validated in DLBCL, with further analysis proving that it was correlated with poor prognosis. It was shown that the overexpression of miR­196a­3p was associated with cell cycle arrest, enhanced apoptosis, and inhibited proliferation in DLBCL cells. Furthermore, ADP ribosylation factor 4 (ARF4) was verified as the downstream target gene of miR­196a­3p. Similar to miR­196a­3p restoration in vitro, endogenous ARF4­knockdown was proven to inhibit cell proliferation through cell cycle arrest and elevate apoptosis in DLBCL. The present results indicated that miR­196a­3p downregulation contributed to the tumorigenesis of DLBCL by targeting ARF4 expression, which may be used as a novel prognostic marker or potential molecular therapeutic target for DLBCL management in the future.


Assuntos
Fatores de Ribosilação do ADP/genética , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/metabolismo , Apoptose/genética , Biópsia , Medula Óssea/patologia , Carcinogênese/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade
13.
J Exp Clin Cancer Res ; 39(1): 237, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33168041

RESUMO

BACKGROUND: In follicular lymphoma (FL), histologic transformation to high-grade FL and diffuse large B-cell lymphoma (DLBCL) is a critical adverse step in disease progression. Activation of the oncogene c-MYC and tumor microenvironment remodeling account for FL progression. A panel of microRNA (miRNA) was downregulated in transformed FL (tFL). METHODS: Differentially expressed miRNAs were systematically compared in 11 lymph nodes from patients at different stages of disease. Expression of miR-7e-5p was analyzed in 46 B-cell lymphomas, including 30 FL tissues and 16 DLBCL tissues. In FL cells, transcriptional regulation of the oncogene c-MYC on its target miR-7e-5p was revealed by Chromatin Immunoprecipitation (ChIP) assay. Exosome, carrying differentially expressed miR-7e-5p was isolated and visualized by transmission electron microscope and fluorescence tracing. The effect of miR-7e-5p on recipient macrophage was determined by target gene quantification, flow cytometry, and TUNEL method in a cocultured system with miR-7e-5p-mimics or inhibitors treatment. Expression of miR-7e-5p targets, macrophage proportions, and clinical parameters were included for correlation analysis. RESULTS: We determined that downregulation of miR-7e-5p, driven by c-MYC overexpression, was associated with poorer prognosis in FL patients. The decreased expression of miR-7e-5p in lymphoma cells led to a reduced exosomal transfer to surrounding macrophages. As a result, the target gene of miR-7e-5p, Fas ligand (FasL), was upregulated and activated the caspase signaling, which led to the apoptosis of M1 macrophages in tumor stroma. Finally, in transformed FL tissues, overexpression of FasL and activation of caspase proteins was detected in tumor stromal macrophages. Downregulation of miR-7e-5p was associated with poorer clinical outcomes. CONCLUSION: Downregulation of exosomal miR-7e-5p induces stromal M1 macrophage apoptosis, which leads to immunosurveillance and transformation of FL.


Assuntos
Proteína Ligante Fas/imunologia , Linfoma Folicular/imunologia , Macrófagos/metabolismo , MicroRNAs/imunologia , Regulação para Baixo , Proteína Ligante Fas/metabolismo , Feminino , Humanos , Linfoma Folicular/genética , Linfoma Folicular/patologia , Macrófagos/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Células Estromais/imunologia , Células Estromais/patologia , Transfecção , Regulação para Cima
15.
Thromb Res ; 192: 3-8, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32407937

RESUMO

OBJECTIVE: To investigate the clinical features of COVID-19 cases in Suzhou China. Biomarkers were screened out of hematological parameters for risk stratification. METHOD: Confirmed COVID-19 adult patients in Suzhou were included. The patient data was collected, and the results of laboratory examinations were compared between the mild/moderate and severe COVID-19 groups. A ROC was calculated to compare the diagnostic performance of candidate indexes, and dynamic levels of hematological indexes were compared between the two groups. RESULT: 75 patients were enrolled, with a mean age of 46.6 ±â€¯14 years, and 45 patients were male. All patients were classified into two groups: the mild/moderate group and the severe group. WBC, neutrophil to lymphocyte ratio (NLR), D-dimer, and fibrinogen levels of the severe group were significantly higher (P < 0.05) than the mild/moderate, and the lymphocyte was lower. The ROC test showed that the hematological parameters had a larger AUC than that of inflammatory factors. There was a significant difference in lymphocyte and fibrinogen levels between the two groups on day 1 (P < 0.05). However, NLR of the severe group was higher than the mild/moderate on days 1, 4 and 14 (P < 0.01), and so was D-dimer on days 1, 7 and 14 (P < 0.05). CONCLUSION: The common COVID-19 abnormal hematological indexes on admission included hyperfibrinogenemia, lymphopenia, the elevation of D-dimer, and leukopenia, which were significantly different between the mild/moderate and severe COVID-19 groups. Furthermore, the dynamic change of NLR and D-dimer level can distinguish severe COVID-19 cases from the mild/moderate.


Assuntos
Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Linfócitos , Neutrófilos , Pneumonia Viral/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , COVID-19 , Teste para COVID-19 , China , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto Jovem
16.
Leukemia ; 34(3): 821-830, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31624374

RESUMO

CD19-redirected CAR-T immunotherapy has emerged as a promising strategy for treatment of B cell lymphoma, however, many patients often relapsed due to antigen loss. Therefore, it is urgently needed to explore other suitable antigens targeted by CAR-T cells to cure B cell lymphoma. Igß is a component of the B cell receptor (BCR) complex, which is highly expressed on the surface of lymphoma cells. In this study, we engineered T cells to express anti-Igß CAR with CD28 costimulatory signaling moiety and observed that Igß-CAR T cells could efficiently recognize and eliminate Igß+ lymphoma cells both in vitro and in two different lymphoma xenograft models. The specificity of Igß-CAR T cells was further confirmed through wild type or mutated Igß gene transduction together with Igß-specific knockout in target cells. Of note, both the in vitro and in vivo effect of Igß CAR-T cells was comparable with that of CD19 CAR-T cells. Importantly, Igß CAR-T cells recognized and eradicated patient-derived lymphoma cells in the autologous setting. Lastly, the safety of anti-Igß CAR-T cells could be further enhanced by introduction of the inducible caspase-9 suicide gene system. Collectively, Igß-specific CAR-T cells may be a promising immunotherapeutic approach for B cell lymphoma.


Assuntos
Antígenos CD79/imunologia , Imunoterapia Adotiva , Linfoma de Células B/imunologia , Linfoma de Células B/terapia , Linfócitos T/imunologia , Animais , Antígenos CD28/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Humanos , Células K562 , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Mutação , Transplante de Neoplasias , Receptores de Antígenos Quiméricos/imunologia
17.
PLoS One ; 14(4): e0215656, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31034481

RESUMO

Data about human trajectories has been widely used to study urban regions that are attractive to researchers and are considered to be hotspots. It is difficult, however, to quantify the function of urban regions based on the varieties of human behavior. In this research, we developed a clustering method to help discover the specific functions that exist within urban regions. This method applies the Gaussian Mixture Model (GMM) to classify regions' inflow and trip count characteristics. It regroups these urban regions using the Pearson Correlation Coefficient (PCC) clustering method based on those typical characteristics. Using a large amount of vehicle trajectory data (approximately 1,500,000 data points) in the Chinese city of Chengdu, we demonstrate that the method can discriminate between urban functional regions, by comparing the proportion of surface objects within each region. This research shows that vehicle trajectory data in different functional urban regions possesses different time-series curves, while similar types of functional regions can be identified by these curves. Compared with remote sensing images and other statistical methods which can provide only static results, our research can provide a timely and effective approach to determine an urban region's functions.


Assuntos
Veículos Automotores/estatística & dados numéricos , População Urbana/estatística & dados numéricos , China , Cidades , Análise por Conglomerados , Humanos , Modelos Estatísticos , Distribuição Normal , Tecnologia de Sensoriamento Remoto , Viagem/estatística & dados numéricos
18.
Cancer Sci ; 110(2): 805-816, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30536996

RESUMO

MicroRNAs, which regulate mRNAs, operate through a variety of signaling pathways to participate in the development of colorectal cancer (CRC). In this study, we found that microRNA (miR)-143-3p expression was significantly lower in both CRC and liver metastatic CRC tissues from liver compared with normal colonic tissues. Functional assays showed that miR-143-3p inhibited CRC cell invasion and migration in vitro. Using a bioinformatics approach, we identified miR-143-3p target mRNAs. Among the candidate targets, only the expression of integrin alpha 6 (ITGA6) and ArfGAP with the SH3 domain and ankyrin repeat and PH domain 3 (ASAP3) were significantly reduced by miR-143-3p mimics as examined by western blot, and the metastasis potential of CRC cells was attenuated by endogenous ITGA6 and ASAP3 knockdown, determined by migration and invasion assays. Both ITGA6 and ASAP3 were upregulated in CRC tissues compared to normal tissues. Analysis of the relationship between clinicopathological features and ITGA6/ASAP3 protein expression in 200 patients with CRC showed a significant difference in positive ITGA6 expression between the early stage (I + II) and the advanced stage (III + IV), and ASAP3 expression levels positively correlated with metastasis in the lymph nodes. These results indicate that miR-143-3p acts as an anti-oncogene by downregulating ITGA6/ASAP3 protein expression and could offer new insight into potential therapeutic targets for CRC.


Assuntos
Movimento Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Ativadoras de GTPase/genética , Integrina alfa6/genética , Metástase Linfática/genética , MicroRNAs/genética , Idoso , Linhagem Celular Tumoral , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HCT116 , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , RNA Mensageiro/genética , Transdução de Sinais/genética , Regulação para Cima/genética
19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 29(6): 481-485, 2017 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28625233

RESUMO

OBJECTIVE: To investigate the association of red cell distribution width (RDW) with prognosis in patients with sepsis. METHODS: Patients with sepsis admitted to intensive care unit (ICU) of the First Hospital of Soochow University from January 2011 to December 2016 were enrolled. All clinical data were collected for participants, which mainly included basic data, main underlying disease, site of infection, acute physiology and chronic health evaluation II(APACHE II) score, blood routine test, biochemical test, blood gas analysis, coagulation index, procalcitonin (PCT), hospitalization days, and 28-day and 90-day mortality. Patients were divided into two groups according to whether the RDW levels were higher than the time of admission or not. Kaplan-Meier survival curve was performed to analyze 28-day and 90-day cumulative survival rates in two groups. Multivariate Cox regression analysis was done to find the independent risk factors of death in patients with sepsis. RESULTS: 196 septic patients were eligible to participate into this study. 150 patients (53.57%) had higher RDW levels than those at the time of admission. Compared to negative or static change of RDW group, positive change of RDW group had higher APACHE II score (20.42±6.29 vs. 16.17±6.37), more percentage of chronic kidney insufficiency (35.24% vs. 19.78%), bloodstream infection (32.38% vs. 15.38%), continuous renal replacement therapy (CRRT: 32.38% vs. 16.48%), higher level of C-reactive protein [CRP (mg/L): 14.71±3.52 vs. 11.15±7.94], and higher serum creatinine [SCr (µmol/L): 128.0 (74.0, 263.5) vs. 90.0 (57.0, 145.5)], PCT [µg/L: 3.45 (2.39, 6.64) vs. 2.35 (0.56, 3.54)], and lactic acid [Lac (mmol/L): 3.40±1.72 vs. 2.70±1.61]; and had lower levels of hematocrit (Hct: 0.357±0.128 vs. 0.437±0.143), hemoglobin [Hb (g/L): 103.60±22.63 vs. 115.67±28.49], platelets [PLT (×109/L): 133.37±87.29 vs. 191.43±87.65], albumin [Alb (g/L): 28.15±5.72 vs. 35.51±5.91], total cholesterol [TC (mmol/L): 2.43±1.12 vs. 3.05±1.55], estimated glomerular filtration rate [eGFR (mL×min-1×1.73 m-2): 82.02±63.90 vs. 125.46±83.47], and oxygenation index [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 229.69±60.61 vs. 264.21±74.78]; and longer time of hospitalization [days: 17.0 (12.0, 21.7) vs. 11.0 (7.0, 18.0)], higher 28-day and 90-day mortality (57.14% vs. 36.26%, 62.86% vs. 47.25%) with statistically significant differences (all P < 0.05). It was shown by Kaplan-Meier survival curve that the 28-day and 90-day cumulative survival rate in positive change of RDW group was significantly lower than that of negative or static change of RDW group (χ 12 = 8.462, χ 22 = 6.411, both P < 0.05). It was shown by multivariate Cox regression that high APACHE II score [odds ratio (OR) = 1.049, 95% confidence interval (95%CI) = 1.010-1.090, P = 0.013] and positive change of RDW (OR = 0.517, 95%CI = 0.280-0.953, P = 0.034) were the risk factors of death in patients with sepsis. CONCLUSIONS: The change of RDW values during hospitalization was related to the poor outcomes in patients with sepsis. The increase of RDW predicts the progress of sepsis and bad prognosis. Serial surveillance of RDW values could provide useful information for long-term prognosis in sepsis.


Assuntos
Sepse , APACHE , Calcitonina , Índices de Eritrócitos , Hospitalização , Humanos , Unidades de Terapia Intensiva , Prognóstico , Estudos Retrospectivos
20.
Sensors (Basel) ; 16(12)2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27916944

RESUMO

Low-cost GPS (receiver) has become a ubiquitous and integral part of our daily life. Despite noticeable advantages such as being cheap, small, light, and easy to use, its limited positioning accuracy devalues and hampers its wide applications for reliable mapping and analysis. Two conventional techniques to remove outliers in a GPS trajectory are thresholding and Kalman-based methods, which are difficult in selecting appropriate thresholds and modeling the trajectories. Moreover, they are insensitive to medium and small outliers, especially for low-sample-rate trajectories. This paper proposes a model-based GPS trajectory cleaner. Rather than examining speed and acceleration or assuming a pre-determined trajectory model, we first use cubic smooth spline to adaptively model the trend of the trajectory. The residuals, i.e., the differences between the trend and GPS measurements, are then further modeled by time series method. Outliers are detected by scoring the residuals at every GPS trajectory point. Comparing to the conventional procedures, the trend-residual dual modeling approach has the following features: (a) it is able to model trajectories and detect outliers adaptively; (b) only one critical value for outlier scores needs to be set; (c) it is able to robustly detect unapparent outliers; and (d) it is effective in cleaning outliers for GPS trajectories with low sample rates. Tests are carried out on three real-world GPS trajectories datasets. The evaluation demonstrates an average of 9.27 times better performance in outlier detection for GPS trajectories than thresholding and Kalman-based techniques.

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