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1.
BMC Cancer ; 24(1): 132, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273254

RESUMO

BACKGROUND: Studies have revealed that acute myeloid leukemia (AML) patients are prone to combined cardiac injury. We aimed to identify hematological risk factors associated with cardiac injury in newly diagnosed AML patients before chemotherapy and develop a personalized predictive model. METHODS: The population baseline, blood test, electrocardiogram, echocardiograph, and genetic and cytogenetic data were collected from newly diagnosed AML patients. The data were subdivided into training and validation cohorts. The independent risk factors were explored by univariate and multivariate logistic regression analysis respectively, and data dimension reduction and variable selection were performed using the least absolute shrinkage and selection operator (LASSO) regression models. The nomogram was generated and the reliability and generalizability were verified by receiver operating characteristic (ROC) curves, the area under the curve (AUC) and calibration curves in an external validation cohort. RESULTS: Finally, 499 AML patients were included. After univariate logistic regression, LASSO regression and multivariate logistic regression analysis, abnormal NT-proBNP, NPM1 mutation, WBC, and RBC were independent risk factors for cardiac injury in AML patients (all P < 0.05). The nomogram was constructed based on the above four variables with high accuracy. The area under the curve was 0.742, 0.750, and 0.706 in the training, internal validation, and external validation cohort, respectively. The calibration curve indicated that the model has good testing capability. The Kaplan-Meier curve showed that the higher the risk of combined cardiac injury in AML patients, the lower their probability of survival. CONCLUSIONS: This prediction nomogram identifies hematological risk factors associated with cardiac injury in newly diagnosed AML patients and can help hematologists identify the risk and provide precise treatment options.


Assuntos
Leucemia Mieloide Aguda , Humanos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , China/epidemiologia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Nomogramas
2.
BMC Oral Health ; 23(1): 605, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644470

RESUMO

INTRODUCTION: This retrospective cohort study aimed to compare the change in upper airway and craniocervical posture after orthodontic treatment between adolescent and adult patients with Class II high-angle malocclusion. METHODS: A total of 12 adolescent (mean ± standard deviation age = 13.0 ± 2.0 years) and 12 adult patients with Class II high-angle malocclusion (mean ± standard deviation age = 23.7 ± 6.4 years) were selected in this study. The lateral cephalograms and cone beam computed tomography images of adolescent and adult patients were taken before and after treatment, which can be employed to evaluate the variables of craniofacial morphology, upper airway, and craniocervical posture through paired t tests, respectively. An independent sample t test was performed to observe the differences between two groups after orthodontic intervention. For adults and adolescents, the correlation between craniofacial morphology, upper airway, and craniocervical posture was determined through Pearson correlation analysis. RESULTS: In all subjects, the improvements in vertical and sagittal facial morphology after treatment were observed. Anterior and inferior movements of the hyoid bone, an increase of upper airway dimension, posterior tipping of the head and a reduction of cervical inclination in the lower and middle segments post-treatment were identified in adolescence (P < 0.05). Adults displayed anterior movements of the hyoid bone, whereas no significant difference was observed in upper airway dimension and craniocervical posture (P < 0.05). Notable differences were identified in the change of hyoid position and airway volume between two groups (P > 0.05). Mandibular plane inclination, growth pattern, occlusal plane inclination, and chin position were all significantly correlated with craniocervical posture in adolescent patients. Besides, the mandibular growth pattern and chin position in adult patients were significantly correlated with craniocervical posture (P < 0.05). CONCLUSIONS: Orthodontic treatment is capable of enhancing the facial profile of patients with skeletal class II high-angle while improving their upper airway morphology and craniocervical posture, where adolescents and adults differ substantially in that the former exhibit a more favorable alteration in the airway-craniocervical functional environment.


Assuntos
Má Oclusão Classe II de Angle , Nariz , Humanos , Adolescente , Adulto , Criança , Adulto Jovem , Projetos Piloto , Estudos Retrospectivos , Assistência Odontológica , Má Oclusão Classe II de Angle/diagnóstico por imagem , Má Oclusão Classe II de Angle/terapia
3.
J Med Virol ; 94(4): 1535-1539, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34850404

RESUMO

The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. Early detection and intervention are key factors for improving outcomes in patients with COVID-19. Real-time reverse transcriptase polymerase chain reaction-based molecular assays and antibody for detecting SARS-CoV-2 in respiratory specimens are the current reference standard for COVID-19 diagnosis. Clinical implications of different specimen types for nucleic acid and antibody testing of COVID-19 in Zhongnan hospital of Wuhan University were analyzed. Compared with health groups, tumor patients had higher rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (+/-) immunoglobulin M (IgM) (+) immunoglobulin G (IgG) (+). The rate of SARS-CoV-2 (-) IgM (+) IgG (-) or SARS-CoV-2 (-) IgM (-) IgG (+) in female was significantly higher than that in male. These results can help governments to take screening measures to prevent the COVID-19 pandemic again.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Neoplasias/epidemiologia , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Teste para COVID-19 , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2/imunologia , Sensibilidade e Especificidade , Distribuição por Sexo , Adulto Jovem
4.
Hematol Oncol ; 40(2): 212-222, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34860428

RESUMO

This study aimed to evaluate the existing staging systems for multiple myeloma (MM) in the real world. From January 2010 to June 2019, we retrospectively analyzed 859 newly diagnosed MM patients from two institutions. Clinical data including laboratory findings, imaging examinations and staging system were obtained by reviewing medical records. Survival distributions were estimated using the Kaplan-Meier curve analysis, and Cox proportional hazards model were used to identified risk factors. The overall survival (OS) of eligible patients was 61.0 months. The Revised International Staging System (R-ISS) had a larger receiver operating characteristic curve area (0.603) than both the International Staging System (0.573) and the Durie Salmon staging system (0.567). In the group receiving immunomodulatory agents-based regimens, the median OS was 92.0 months in R-ISS I, 63.0 months in R-ISS II and 18.0 months in R-ISS III (p < 0.0001). In the group receiving proteasome inhibitors-based regimens, the median OS was 102.0 months in R-ISS I, 63.0 months in R-ISS II and 22.0 months in R-ISS III (p < 0.0001). In different subgroups grouped according to age, hemoglobin (HGB), creatinine, and Ca, R-ISS also had a good stratification effect. Patients in R-ISS II, which accounted for 69.9% of all patients, were further analyzed. Univariate and multivariate Cox analyses revealed that age >65 years (p = 0.001), HGB < 100 g/L (p < 0.001), elevated LDH (p = 0.001), and Ca (p = 0.010) were independent predictors of worse prognosis within R-ISS II. To conclusion, R-ISS remains a valuable staging system in the real world of the novel drug era. However, patients classified as R-ISS II still have great heterogeneity.


Assuntos
Mieloma Múltiplo , Idoso , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estadiamento de Neoplasias , Prognóstico , Inibidores de Proteassoma , Estudos Retrospectivos
5.
J Cell Mol Med ; 23(2): 1509-1516, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30484952

RESUMO

Novel nude mice model of human NK/T cell lymphoma were established by subcutaneously injecting two NK/T cell lymphoma cell lines into the right axillary region of mice and successful passages were completed by injecting cell suspension which was obtained through a 70-µm cell strainer. These mice models and corresponding cell clones have been successfully developed for more than 8 generations. The survival rates of both resuscitation and transplantation in NKYS and YT models were 90% and 70% correspondingly. Pathologically, the tumour cells in all passages of the lymphoma-bearing mice and cell lines obtained from tumours were parallel to initial cell lines. Immunologically, the tumour cells expressed the characteristics of the primary and essential NK/T lymphomas. The novel mice models maintained the essential features of human NK/T cell lymphoma, and they would be ideal tools in vivo for further research of human NK/T cell lymphoma.


Assuntos
Modelos Animais de Doenças , Células Matadoras Naturais/metabolismo , Linfoma Extranodal de Células T-NK/patologia , Animais , Linhagem Celular Tumoral , Herpesvirus Humano 4/patogenicidade , Humanos , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/virologia , Camundongos , Camundongos Nus
7.
Opt Express ; 23(3): 2639-46, 2015 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-25836127

RESUMO

We propose a planar dielectric reflector with focusing ability using concentric circular subwavelength gratings (CC-SWGs). The two-dimensional focusing ability of CC-SWGs is investigated by the rigorous coupled-wave analysis (RCWA) and finite element method (FEM). By designing the concentric circular pattern of the grating surface, a focusing reflector with high numerical aperture (NA) and high reflectivity is constructed. A CC-SWG reflector with a diameter of 32.6µm and a focal length of 6µm is investigated, which exhibits high focusing ability at normal incidence with a radially polarized plane wave. At the reflection focal plane, the full-width-half-maximum (FWHM) of the electric field intensity is 0.89µm. Numerical aperture value as high as 0.93 is achieved for the reflector with very high reflectivity of 92%.

8.
Opt Lett ; 39(8): 2447-50, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24979015

RESUMO

A reflection-enhanced dual-absorption InP-PIN/GaAs-DBR photodetector was fabricated and characterized. The photodetector is monolithically integrated using a heteroepitaxy growth of an InGaAs/InP dual-absorption "PINIP" structure on the GaAs/AlGaAs Bragg reflectors. These features lead to an increase in quantum efficiency over a wide wavelength range while maintaining a high speed. The measured quantum efficiency was increased by 48.8% in comparison with that without reflectors. A quantum efficiency of 64% at a wavelength of 1522 nm and a 3 dB bandwidth of 26 GHz at a reverse bias of 3 V were simultaneously obtained in the device.

9.
Oncogene ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877132

RESUMO

Treatment-induced neuroendocrine prostate cancer (t-NEPC) often arises from adenocarcinoma via lineage plasticity in response to androgen receptor signaling inhibitors, such as enzalutamide. However, the specific regulators and targets involved in the transition to NEPC are not well understood. Plexin D1 (PLXND1) is a cellular receptor of the semaphorin (SEMA) family that plays important roles in modulating the cytoskeleton and cell adhesion. Here, we found that PLXND1 was highly expressed and positively correlated with neuroendocrine markers in patients with NEPC. High PLXND1 expression was associated with poorer prognosis in prostate cancer patients. Additionally, PLXND1 was upregulated and negatively regulated by androgen receptor signaling in enzalutamide-resistant cells. Knockdown or knockout of PLXND1 inhibited neural lineage pathways, thereby suppressing NEPC cell proliferation, patient derived xenograft (PDX) tumor organoid viability, and xenograft tumor growth. Mechanistically, the heat shock protein 70 (HSP70) regulated PLXND1 protein stability through degradation, and inhibition of HSP70 decreased PLXND1 expression and NEPC organoid growth. In summary, our findings indicate that PLXND1 could serve as a promising therapeutic target and molecular marker for NEPC.

10.
Res Sq ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38585965

RESUMO

Treatment-induced neuroendocrine prostate cancer (t-NEPC) often arises from adenocarcinoma via lineage plasticity in response to androgen receptor signaling inhibitors, such as enzalutamide. However, the specific regulators and targets involved in the transition to NEPC are not well understood. Plexin D1 (PLXND1) is a cellular receptor of the semaphorin (SEMA) family that plays important roles in modulating the cytoskeleton and cell adhesion. Here, we found that PLXND1 is highly expressed and positively correlated with neuroendocrine markers in patients with NEPC. High PLXND1 expression is associated with poorer prognosis in prostate cancer patients. Additionally, PLXND1 was upregulated and negatively regulated by androgen receptor signaling in enzalutamide-resistant cells. Knockdown or knockout of PLXND1 inhibit neural lineage pathways, suppressing NEPC cell proliferation, PDX tumor organoid viability, and xenograft tumor growth. Mechanistically, the chaperone protein HSP70 regulates PLXND1 protein stability through degradation, and inhibition of HSP70 decreases PLXND1 expression and NEPC organoid growth. In summary, our findings suggest that PLXND1 could be a new therapeutic target and molecular indicator for NEPC.

11.
J Vis Exp ; (182)2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35499349

RESUMO

Fluorescence in situ hybridization (FISH) detection is an indispensable method in genetic risk stratification in multiple myeloma (MM), which is one of the most common hematological malignancies. The identifying characteristic of MM is accumulated malignant plasma cells in bone marrow. FISH reports for MM mainly focus on purified or identified clonal plasma cells, rather than all nucleated cells, by sorting with anti-CD138 magnetic beads or marking with cytoplasmic immunoglobulin light chain κ or λ. Bone marrow interphase nuclei are usually obtained from fresh bone marrow cells. However, satisfactory enrichment of plasma cell specimens requires large amounts of fresh heparin anti-coagulated bone marrow, which cannot be obtained in the case of difficult bone marrow extraction or a bone marrow dry tap. Herein, we establish a novel method to improve the success of FISH detection on stained or unstained bone marrow smears. Bone marrow smears are easier to obtain than anticoagulated bone marrow specimens.


Assuntos
Medula Óssea , Mieloma Múltiplo , Humanos , Hibridização in Situ Fluorescente , Interfase , Mieloma Múltiplo/genética , Plasmócitos
12.
Front Oncol ; 12: 772015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372017

RESUMO

Purpose: The study aimed to assess factors associated with early infection and identify patients at high risk of developing infection in multiple myeloma. Methods: The study retrospectively analyzed patients with MM seen at two medical centers between January 2013 and June 2019. One medical center reported 745 cases, of which 540 of the cases were available for analysis and were further subdivided into training cohort and internal validation cohort. 169 cases from the other medical center served as an external validation cohort. The least absolute shrinkage and selection operator (Lasso) regression model was used for data dimension reduction, feature selection, and model building. Results: Bacteria and the respiratory tract were the most common pathogen and localization of infection, respectively. In the training cohort, PS≥2, HGB<35g/L of the lower limit of normal range, ß2MG≥6.0mg/L, and GLB≥2.1 times the upper limit of normal range were identified as factors associated with early grade ≥ 3 infections by Lasso regression. An infection risk model of MM (IRMM) was established to define high-, moderate- and low-risk groups, which showed significantly different rates of infection in the training cohort (46.5% vs. 22.1% vs. 8.8%, p<0.0001), internal validation cohort (37.9% vs. 24.1% vs. 13.0%, p=0.009) and external validation cohort (40.0% vs. 29.2% vs. 8.5%, p=0.0003). IRMM displayed good calibration (p<0.05) and discrimination with AUC values of 0.76, 0.67 and 0.71 in the three cohorts, respectively. Furthermore, IRMM still showed good classification ability in immunomodulatory (IMiD) based regimens, proteasome-inhibitors (PI) based regimens and combined IMiD and PI regimens. Conclusion: In this study, we determined risk factors for early grade ≥ 3 infection and established a predictive model to help clinicians identify MM patients with high-risk infection.

13.
Front Med (Lausanne) ; 9: 844350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755044

RESUMO

The relationship between newly diagnosed acute leukemia (AL) and heart-related lesions remains unclear. This study aimed to investigate baseline cardiac function and risk of cardiovascular diseases (CVDs) in patients with new-onset AL, and provide data on cardiac management strategies for patients with AL. We retrospectively collected data on baseline characteristics, echocardiography, and biochemical blood indicators (e.g., myocardial enzymes) from 408 patients, 200 with newly diagnosed AL, 103 with coronary artery disease (CAD), and 105 controls from January 1, 2015 to August 31, 2019. The creatine kinase isoenzyme myocardial band, lactate dehydrogenase, highly sensitive troponin-I, and B-type natriuretic peptide levels and left ventricular internal diameter (LVID) were significantly higher in patients with newly diagnosed AL than in the control group. The degree of cardiac damage was lower in newly diagnosed AL patients than in CAD patients. The best predictor of heart damage was LVID (AUC [area under the curve] = 0.709; 95% CI [confidence interval]: 0.637-0.781; p < 0.001), and independent prognostic risk factors were age and ejection fraction (HR [hazard ratio] = 1.636; 95% CI: 1.039-2.575; p = 0.033). The ratio of leukemia blasts among patients with AL was positively correlated with cardiac damage. Our data indicated that newly diagnosed AL patients had certain myocardial damage before treatment. Clinicians need to pay attention to these manifestations, which may be related to the prognosis.

14.
Front Cell Dev Biol ; 9: 570179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34012958

RESUMO

Umbilical cord mesenchymal stem cells (UC-MSCs) are a class of multifunctional stem cells isolated and cultured from umbilical cord. They possessed the characteristics of highly self-renewal, multi-directional differentiation potential and low immunogenicity. Its application in the field of tissue engineering and gene therapy has achieved a series of results. Recent studies have confirmed their characteristics of inhibiting tumor cell proliferation and migration to nest of cancer. The ability of UC-MSCs to support hematopoietic microenvironment and suppress immune system suggests that they can improve engraftment after hematopoietic stem cell transplantation, which shows great potential in treatment of hematologic diseases. This review will focus on the latest advances in biological characteristics and mechanism of UC-MSCs in treatment of hematological diseases.

15.
Front Immunol ; 12: 580147, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936026

RESUMO

The coronavirus disease 2019 (COVID-19) is widely spread and remains a global pandemic. Limited evidence on the systematic evaluation of the impact of treatment regimens on antibody responses exists. Our study aimed to analyze the role of antibody response on prognosis and determine factors influencing the IgG antibodies' seroconversion. A total of 1,111 patients with mild to moderate COVID-19 symptoms admitted to Leishenshan Hospital in Wuhan were retrospectively analyzed. A serologic SARS-CoV-2 IgM/IgG antibody test was performed on all the patients 21 days after the onset of symptoms. Patient clinical characteristics were compared. In the study, 42 patients progressed to critical illness, with 6 mortalities reported while 1,069 patients reported mild to moderate disease. Advanced age (P = 0.028), gasping (P < 0.001), dyspnea (P = 0.024), and IgG negativity (P = 0.006) were associated with progression to critical illness. The mortality rate in critically ill patients with IgG antibody was 6.45% (95% CI 1.12-22.84%) and 36.36% (95% CI 12.36-68.38%) in patients with no IgG antibody (P = 0.003). Symptomatic patients were more likely to develop IgG antibody responses than asymptomatic patients. Using univariable analysis, fever (P < 0.001), gasping (P = 0.048), cancer (P < 0.001), cephalosporin (P = 0.015), and chloroquine/hydroxychloroquine (P = 0.021) were associated with IgG response. In the multivariable analysis, fever, cancer, cephalosporins, and chloroquine/hydroxychloroquine correlated independently with IgG response. We determined that the absence of SARS-CoV-2 antibody IgG in the convalescent stage had a specific predictive role in critical illness progression. Importantly, risk factors affecting seropositivity were identified, and the effect of antimalarial drugs on antibody response was determined.


Assuntos
Anticorpos Antivirais/imunologia , Antimaláricos/efeitos adversos , COVID-19/imunologia , Imunoglobulina G/imunologia , Adolescente , Adulto , Idoso , COVID-19/complicações , COVID-19/mortalidade , Cefalosporinas/efeitos adversos , China , Cloroquina/efeitos adversos , Convalescença , Feminino , Febre/complicações , Febre/virologia , Humanos , Hidroxicloroquina/efeitos adversos , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/complicações , Neoplasias/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Soroconversão , Testes Sorológicos , Tratamento Farmacológico da COVID-19
16.
Front Med (Lausanne) ; 8: 762419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004735

RESUMO

Background: Thrombocytosis is a common symptom in myeloproliferative neoplasms (MPN), and excessive proliferation may deteriorate into thrombosis, bleeding, myelofibrosis, and may ultimately convert to acute leukemia. This study aimed to investigate the collection efficiency of plateletpheresis (CEPP) and factors influencing its efficacy in patients with thrombocytosis. Materials and Methods: From September 2010 to December 2016, 81 patients from two institutions in China with myeloproliferative neoplasms and thrombocytosis accompanied by severe symptoms were treated with plateletpheresis by Fresenius COM. TEC machine. Results: After apheresis, the median CEPP was 20.71% (IQR: 9.99-36.69%) and median PLT reduction rate was 25.87% (IQR: 21.78-36.23%). Further analysis showed that no significant difference was observed between PLT count with 800-1,000 × 109/L and > 1,000 × 109/L. The PLT counts significantly decreased (P < 0.001) after plateletpheresis, the red blood cell (RBC), white blood cell (WBC), hemoglobin (HGB), and hematocrit (HCT) levels showed no significant differences before- or after- plateletpheresis. Multivariate analysis showed that female sex (P = 0.009) and HGB (P = 0.010) before apheresis were associated with CEPP. Female (P = 0.022), HCT (P = 0.001) and blood volume (P = 0.015) were associated with the PLT reduction rate. Furthermore, symptoms were relieved after apheresis in patients whose PLT count was 800-1,000 × 109/L accompanied with symptoms. Conclusions: It is reasonable to perform plateletpheresis when the PLT count is over 800 × 109/L and patients are complicated by clinical symptoms such as dizziness, headache, somnolence, and stupor. Plateletpheresis is effective in removing PLTs especially in females with high HGB.

17.
Mol Med Rep ; 22(5): 4101-4106, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000236

RESUMO

Yes­associated protein (YAP) acts as a transcriptional co­activator in gene expression and cell proliferation control by binding to the transcriptional factor TEA domain (TEAD) of the Hippo signaling pathway in the nucleus, and also acts as a regulator by binding to another transcriptional co­activator, ß­catenin of the Wnt signaling pathway. Whether YAP preferentially acts as a transcriptional co­regulator of the activity of the Hippo signaling pathway or as a regulator in the Wnt signaling pathway depends on the cell type. Nuclear YAP upregulates the expression of ß­catenin, while cytoplasmic YAP has a negative effect on this expression. The present mini­review focused on the important roles of YAP and further discussed the cross­links between the Wnt and Hippo signaling pathways. The Wnt and Hippo signaling pathways are both related to the development of fibrosis or cancer. The current review discussed treatment approaches for these conditions based on the two pathways. YAP, the intersection of these two signaling pathways, has the potential to be developed as a novel treatment target, according to previous basic studies on fibroblasts and cancer cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Animais , Fibrose , Regulação da Expressão Gênica , Via de Sinalização Hippo , Humanos , Especificidade de Órgãos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Wnt/metabolismo , Proteínas de Sinalização YAP
18.
EClinicalMedicine ; 24: 100426, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32766541

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been widely spread and caused tens of thousands of deaths, especially in patients with severe COVID-19. This analysis aimed to explore risk factors for mortality of severe COVID-19, and establish a scoring system to predict in-hospital deaths. METHODS: Patients with COVID-19 were retrospectively analyzed and clinical characteristics were compared. LASSO regression as well as multivariable analysis were used to screen variables and establish prediction model. FINDINGS: A total of 2529 patients with COVID-19 was retrospectively analyzed, and 452 eligible severe COVID-19 were used for finally analysis. In training cohort, the median age was 66•0 years while it was 73•0 years in non-survivors. Patients aged 60-75 years accounted for the largest proportion of infected populations and mortality toll. Anti-SARS-CoV-2 antibodies were monitored up to 54 days, and IgG levels reached the highest during 20-30 days. No differences were observed of antibody levels between severe and non-severe patients. About 60.2% of severe patients had complications. Among acute myocardial injury (AMI), acute kidney injury (AKI) and acute liver injury (ALI), the heart was the earliest injured organ, whereas the time from AKI to death was the shortest. Age, diabetes, coronary heart disease (CHD), percentage of lymphocytes (LYM%), procalcitonin (PCT), serum urea, C reactive protein and D-dimer (DD), were identified associated with mortality by LASSO binary logistic regression. Then multivariable analysis was performed to conclude that old age, CHD, LYM%, PCT and DD remained independent risk factors for mortality. Based on the above variables, a scoring system of COVID-19 (CSS) was established to divide patients into low-risk and high-risk groups. This model displayed good discrimination (AUC=0·919) and calibration (P=0·264). Complications in low-risk and high-risk groups were significantly different (P<0·05). Use of corticosteroids in low-risk groups increased hospital stays by 4·5 days (P=0·036) and durations of disease by 7·5 days (P=0·012) compared with no corticosteroids. INTERPRETATION: Old age, CHD, LYM%, PCT and DD were independently related to mortality. CSS was useful for predicting in-hospital mortality and complications, and it could help clinicians to identify high-risk patients with poor prognosis. FUNDING: This work was supported by the Key Project for Anti-2019 novel Coronavirus Pneumonia from the Ministry of Science and Technology, China (grant number 2020YFC0845500).

19.
Oxid Med Cell Longev ; 2020: 1295984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33425206

RESUMO

Acute myeloid leukemia (AML) is a hematological malignancy with a poor prognosis attributed to elevated reactive oxygen species (ROS) levels. Thus, agents that inhibit ROS generation in AML should be exploited. Azelaic acid (AZA), a small molecular compound, can scavenge ROS and other free radicals, exerting antitumor effects on various tumor cells. Herein, this study evaluated the antileukemic activity of AZA against AML via regulation of the ROS signaling pathway. We found that AZA reduced intracellular ROS levels and increased total antioxidant capacity in AML cell lines and AML patient cells. AZA suppressed the proliferation of AML cell lines and AML patient cells, expending minimal cytotoxicity on healthy cells. Laser confocal microscopy showed that AZA-treated AML cells surged and ruptured gradually on microfluidic chips. Additionally, AZA promoted AML cell apoptosis and arrested the cell cycle at the G1 phase. Further analysis demonstrated that peroxiredoxin (Prdx) 2 and Prdx3 were upregulated in AZA-treated AML cells. In vivo, AZA prolonged survival and attenuated AML by decreasing CD33+ immunophenotyping in the bone marrow of a patient-derived xenograft AML model. Furthermore, mice in the AZA-treated group had an increased antioxidant capacity and Prdx2/Prdx3 upregulation. The findings indicate that AZA may be a potential agent against AML by regulating the Prdxs/ROS signaling pathway.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Ácidos Dicarboxílicos/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Peroxirredoxina III/metabolismo , Peroxirredoxinas/metabolismo , Espécies Reativas de Oxigênio , Animais , Apoptose , Medula Óssea/imunologia , Medula Óssea/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Imunofenotipagem , Camundongos , Transplante de Neoplasias , Prognóstico , Transdução de Sinais , Células THP-1 , Células U937
20.
Virulence ; 11(1): 1569-1581, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33172355

RESUMO

A pandemic designated as Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Up to date, there is no efficient biomarker for the timely prediction of the disease progression in patients. To analyze the inflammatory profiles of COVID-19 patients and demonstrate their implications for the illness progression of COVID-19. Retrospective analysis of 3,265 confirmed COVID-19 cases hospitalized between 10 January 2020, and 26 March 2020 in three medical centers in Wuhan, China. Patients were diagnosed as COVID-19 and hospitalized in Leishenshan Hospital, Zhongnan Hospital of Wuhan University and The Seventh Hospital of Wuhan, China. Univariable and multivariable logistic regression models were used to determine the possible risk factors for disease progression. Moreover, cutoff values, the sensitivity and specificity of inflammatory parameters for disease progression were determined by MedCalc Version 19.2.0. Age (95%CI, 1.017 to 1.048; P < 0.001), serum amyloid A protein (SAA) (95%CI, 1.216 to 1.396; P < 0.001) and erythrocyte sedimentation rate (ESR) (95%CI, 1.006 to 1.045; P < 0.001) were likely the risk factors for the disease progression. The Area under the curve (AUC) of SAA for the progression of COVID-19 was 0.923, with the best predictive cutoff value of SAA of 12.4 mg/L, with a sensitivity of 83.9% and a specificity of 97.67%. SAA-containing parameters are novel promising ones for predicting disease progression in COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Idoso , Área Sob a Curva , Betacoronavirus/genética , Biomarcadores , Sedimentação Sanguínea , Proteína C-Reativa/análise , COVID-19 , China , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Laringe/virologia , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Valor Preditivo dos Testes , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Sensibilidade e Especificidade , Proteína Amiloide A Sérica/análise
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