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BACKGROUND: Caroli's disease (CD) is a rare congenital disorder. The early diagnosis of the disease and differentiation of types I and II are of extreme importance to patient survival. This study was designed to review and discuss observations in 30 patients with CD and to clarify the clinical characteristics of the disease. METHODS: The demographic and clinical features, laboratory indicators, imaging findings and pathology results for 30 patients with CD were reviewed retrospectively. RESULTS: Caroli's disease can occur at any age. The average age of onset in the study cohort was 24 years. Patients who presented with symptoms before the age of 40 years were more likely to develop type II CD. Approximately one-third of patients presented without positive signs at original diagnosis and most of these patients were found to have type I CD on pathology. Anaemia, leucopoenia and thrombocytopoenia were more frequent in patients with type II than type I CD. Magnetic resonance cholangiopancreatography (MRCP) and computed tomography (CT) examinations were most useful in diagnosing CD. CONCLUSIONS: No typical symptoms, signs or laboratory indicators are able to distinguish CD from other conditions. Both MRCP and CT were most valuable in diagnosis. The two types of CD may be differentiated by age of onset and routine blood tests.
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Doença de Caroli/classificação , Doença de Caroli/diagnóstico , Diagnóstico por Imagem/métodos , Progressão da Doença , Adolescente , Adulto , Fatores Etários , Idoso , Doença de Caroli/terapia , Criança , Pré-Escolar , Colangiopancreatografia por Ressonância Magnética/métodos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Doenças Raras , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Índice de Gravidade de Doença , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia Doppler , Adulto JovemRESUMO
E-commerce has the potential to address problems in the agricultural supply chain and support the implementation of rural revitalization strategies. Previous research has largely focused on the business models of rural e-commerce platforms, but has not examined the mechanisms by which they can optimize and reconfigure the agricultural supply chain. This study aims to fill this gap through a case study of Tudouec, a potato e-commerce platform in Inner Mongolia, China. The study employs a single-case study method and utilizes data from interviews, fieldwork, and secondary sources. The findings show that Tudouec is a multi-functional platform offering technical support, warehousing, logistics, supply chain finance, and insurance, among other services. It not only serves as a multi-channel information management platform, but also enhances supply chain capabilities through the interaction of information flow with capital and material flows. This rural e-commerce model addresses the limitations of traditional agricultural models and promotes poverty reduction and rural revitalization. The study's main contribution is in demonstrating the potential for the Tudouec model to be applied to other agricultural products and in other developing countries.
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Comércio , Pobreza , Humanos , População Rural , Emprego , ChinaRESUMO
YTHDF1 is a well-characterized m6A reader protein that is essential for protein translation, stem cell self-renewal, and embryonic development. YTHDF1 regulates target gene expression by diverse molecular mechanisms, such as promoting protein translation or modulating the stability of mRNA. The cellular levels of YTHDF1 are precisely regulated by a complicated transcriptional, post-transcriptional, and post-translational network. Very solid evidence supports the pivotal role of YTHDF1 in embryonic development and human cancer progression. In this review, we discuss how YTHDF1 influences both the physiological and pathological biology of the central nervous, reproductive and immune systems. Therefore we focus on some relevant aspects of the regulatory role played by YTHDF1 as gene expression, complex cell networking: stem cell self-renewal, embryonic development, and human cancers progression. We propose that YTHDF1 is a promising future cancer biomarker for detection, progression, and prognosis. Targeting YTHDF1 holds therapeutic potential, as the overexpression of YTHDF1 is associated with tumor resistance to chemotherapy and immunotherapy.
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Background and aims: The outcomes of current treatment for non-small cell lung cancer (NSCLC) are unsatisfactory and development of new and more efficacious therapeutic strategies are required. The Notch pathway, which is necessary for cell survival to avert apoptosis, induces the resistance of cancer cells to antitumour drugs. Notch pathway activation is controlled by the cleavage of Notch proteins/receptors mediated by A disintegrin and metalloproteinase 17 (ADAM17); therefore, ADAM17 is a reliable intervention target for anti-tumour therapy to overcome the drug resistance of cancer cells. This work aims to develop and elucidate the activation of Compound 2b, a novel-structured small-molecule inhibitor of ADAM17, which was designed and developed and its therapeutic efficacy in NSCLC was assessed via multi-assays. Methods and results: A lead compound for a potential inhibitor of ADAM17 was explored via pharmacophore modelling, molecular docking, and biochemical screening. It was augmented by substituting two important chemical groups [R1 and R2 of the quinoxaline-2,3-diamine (its chemical skeleton)]; subsequently, serial homologs of the lead compound were used to obtain anoptimized compound (2b) with high inhibitory activity compared with leading compound against ADAM17 to inhibit the cleavage of Notch proteins and the accumulation of the Notch intracellular domain in the nuclei of NSCLC cells. The inhibitory activity of compound 2b was demonstrated by quantitative polymerase chain reaction and Western blotting. The specificity of compound 2b on ADAM17 was confirmed via point-mutation. Compound 2b enhanced the activation of antitumor drugs on NSCLC cells, in cell lines and nude mice models, by targeting the ADAM17/Notch pathway. Conclusion: Compound 2b may be a promising strategy for NSCLC treatment.
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BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for primary hepatocellular carcinoma (PHC). Radioactive iodine therapy has been used in the treatment of advanced PHC, especially in patients with portal vein tumor thrombosis. However, data on the therapeutic effect of TACE combined with radioactive iodine therapy in PHC are scarce. AIM: To investigate the clinical efficacy of TACE combined with radioactive iodine implantation therapy in advanced PHC via perfusion computed tomography (CT). METHODS: For this study, 98 advanced PHC patients were recruited and divided randomly into the study and control groups. Patients in the study group were treated with TACE combined radioactive iodine implantation therapy. Patients in the control group were treated with only TACE. The tumor lesion length, clinical effect, serum alpha-fetoprotein (AFP) and CT perfusion parameters were compared before and after therapy, and statistical analysis was performed. RESULTS: There was no significant difference in tumor length and serum AFP between the study and control groups (P > 0.05) before treatment. However, the tumor length and serum AFP in the study group were lower than those in the control group 1 mo and 3 mo after therapy. After 3 mo of treatment, the complete and partial remission rate of the study group was 93.88%, which was significantly higher than the control group (77.55%) (P < 0.05). Before treatment, there were no significant differences between the two groups on the perfusion CT variables, including the lesion blood volume, permeability surface, blood flow, hepatic artery flow and mean transit time (P > 0.05). After 3 mo of treatment, all perfusion CT variables were lower in the study group compared to the control group (P < 0.05). The survival time of patients in the study group was 22 mo compared to 18 mo in the control group, which was significantly different [log rank (Mantel-Cox) = 4.318, P = 0.038]. CONCLUSION: TACE combined with radioactive iodine implantation in the treatment of advanced PHC can inhibit the formation of blood vessels in tumor tissue and reduce the perfusion level of tumor lesions, thereby improving the clinical efficacy and prolonging the survival time of patients.
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Long noncoding RNAs (lncRNAs) reportedly play critical roles in the pathogenesis of various cancers, including lung adenocarcinoma (LUAD). However, the expression level, clinical significance, and potential function of lncRNA-AC092718.4 in LUAD remain unclear. In this study, we found that AC092718.4 was highly expressed in LUAD and high expression of AC092718.4 was correlated with poor overall survival (OS) and disease-specific survival (DSS) in LUAD. Cox regression analysis confirmed that AC092718.4 was an independent factor for LUAD prognosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that AC092718.4 was involved in the PI3K-Akt signaling pathway, Th17 cell differentiation, and cell apoptosis. AC092718.4 expression was correlated with immune cell infiltration. Finally, we found that the knockdown of AC092718.4 inhibited lung adenocarcinoma (LUAD) cell growth and promote cell apoptosis. Our findings confirmed that AC092718.4 may serve as a potential prognostic biomarker in LUAD.
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Adenocarcinoma , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Prognóstico , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases , Pulmão/patologia , Adenocarcinoma/genética , BiomarcadoresRESUMO
Pathologies associated with sarcopenia include decline in muscular strength, lean mass and regenerative capacity. Despite the substantial impact on quality of life, no pharmacological therapeutics are available to counteract the age-associated decline in functional capacity and/or, resilience. Evidence suggests immune-secreted cytokines can improve muscle regeneration, a strategy which we leverage in this study by rescuing the age-related deficiency in Meteorin-like through several in vivo add-back models. Notably, the intramuscular, peptide injection of recombinant METRNL was sufficient to improve muscle regeneration in aging. Using ex vivo media exchange and in vivo TNF inhibition, we demonstrate a mechanism of METRNL action during regeneration, showing it counteracts a pro-fibrotic gene program by triggering TNFα-induced apoptosis of fibro/adipogenic progenitor cells. These findings demonstrate therapeutic applications for METRNL to improve aged muscle, and show Fibro/Adipogenic Progenitors are viable therapeutic targets to counteract age-related loss in muscle resilience.
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Músculo Esquelético , Qualidade de Vida , Músculo Esquelético/fisiologia , Adipogenia , Células-Tronco , CitocinasRESUMO
RYR2 mutation is clinically frequent in non-small cell lung cancer (NSCLC) with its function being elusive. We downloaded lung squamous cell carcinoma and lung adenocarcinoma samples from the TCGA database, split the samples into RYR2 mutant group (n = 337) and RYR2 wild group (n = 634), and established Kaplan-Meier curves. The results showed that RYR2 mutant group lived longer than the wild group (p = 0.027). Weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs) yielded prognosis-related genes. Five mRNAs and 10 lncRNAs were selected to build survival prognostic models with other clinical features. The AUCs of 2 models are 0.622 and 0.565 for predicting survival at 3 years. Among these genes, the AUCs of DKK1 and GS1-115G20.1 expression levels were 0.607 and 0.560, respectively, which predicted the 3-year survival rate of NSCLC sufferers. GSEA identified an association of high DKK1 expression with TP53, MTOR, and VEGF expression. Several target miRNAs interacting with GS1-115G20.1 were observed to show the relationship with the phenotype, treatment, and survival of NSCLC. NSCLC patients with RYR2 mutation may obtain better prognosis by down-regulating DKK1 and up-regulating GS1-115G20.1.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutação , Prognóstico , Regulação para CimaRESUMO
Objective: Infiltrating immune and stromal cells are essential for osteosarcoma progression. This study set out to analyze immune-stromal score-based gene signature and molecular subtypes in osteosarcoma. Methods: The immune and stromal scores of osteosarcoma specimens from the TARGET cohort were determined by the ESTIMATE algorithm. Then, immune-stromal score-based differentially expressed genes (DEGs) were screened, followed by univariate Cox regression analysis. A LASSO regression analysis was applied for establishing a prognostic model. The predictive efficacy was verified in the GSE21257 dataset. Associations between the risk scores and chemotherapy drug sensitivity, immune/stromal scores, PD-1/PD-L1 expression, immune cell infiltrations were assessed in the TARGET cohort. NMF clustering analysis was employed for characterizing distinct molecular subtypes based on immune-stromal score-based DEGs. Results: High immune/stromal scores exhibited the prolonged survival duration of osteosarcoma patients. Based on 85 prognosis-related stromal-immune score-based DEGs, a nine-gene signature was established. High-risk scores indicated undesirable prognosis of osteosarcoma patients. The AUCs of overall survival were 0.881 and 0.849 in the TARGET cohort and GSE21257 dataset, confirming the well predictive performance of this signature. High-risk patients were more sensitive to doxorubicin and low-risk patients exhibited higher immune/stromal scores, PD-L1 expression, and immune cell infiltrations. Three molecular subtypes were characterized, with distinct clinical outcomes and tumor immune microenvironment. Conclusion: This study developed a robust prognostic gene signature as a risk stratification tool and characterized three distinct molecular subtypes for osteosarcoma patients based on immune-stromal score-based DEGs, which may assist decision-making concerning individualized therapy and follow-up project.
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The prognostic role and diagnostic ability of coronavirus disease 2019 (COVID-19) disease indicators are not elucidated, thus, the current study aimed to investigate the prognostic role and diagnostic ability of several COVID-19 disease indicators including the levels of oxygen saturation, leukocytes, lymphocytes, albumin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer in patients with COVID-19. The levels of oxygen saturation, lymphocytes, and albumin were significantly higher in the common and severe clinical type patients compared with those in critical type patients. However, levels of leukocytes, CRP, IL-6, and D-dimer were significantly lower in the common and severe type patients compared with those in critical type patients (P < 0.001). Moreover, the current study demonstrated that the seven indicators have good diagnostic and prognostic powers in patients with COVID-19. Furthermore, a two-indicator (CRP and D-dimer) prognostic signature in training and testing datasets was constructed and validated to better understand the prognostic role of the indicators in COVID-19 patients. The patients were classified into high-risk and low-risk groups based on the median-risk scores. The findings of the Kaplan-Meier curve analysis indicated a significant divergence between the high-risk and low-risk groups. The findings of the receiver operating curve (ROC) analysis indicated the good performance of the signature in the prognosis prediction of COVID-19. In addition, a nomogram was constructed to assist clinicians in developing clinical decision-making for COVID-19 patients. In conclusion, the findings of the current study demonstrated that the seven indicators are potential diagnostic markers for COVID-19 and a two-indicator prognostic signature identification may improve clinical management for COVID-19 patients.
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The transcription factor ETS-1 (E26 transformation specific sequence 1) is the key regulator for malignant tumor cell proliferation and invasion by mediating the transcription of the invasion/migration related factors, e.g. MMPs (matrix metalloproteinases). This work aims to identify the novel small molecule inhibitors of ETS-1 using a small molecule compound library and to study the inhibitors' antitumor activity against hepatocellular carcinoma (HCC). The luciferase reporter is used to examine the inhibition and activation of ETS-1's transcription factor activity in HCC cells, including a highly invasive HCC cell line, MHCC97-H, and five lines of patient-derived cells. The inhibition of the proliferation of HCC cells is examined using the MTT assay, while the invasion of HCC cells is examined using the transwell assay. The anti-tumor activity of the selected compound on HCC cells is also examined in a subcutaneous tumor model or intrahepatic tumor model in nude mice. The results show that for the first time, four compounds, EI1~EI-4, can inhibit the transcription factor activation of ETS-1 and the proliferation or invasion of HCC cells. Among the four compounds, EI-4 has the best activation. The results from this paper contribute to expanding our understanding of ETS-1 and provide alternative, the safer and more effective, HCC molecular therapy strategies.
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Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Proteína Proto-Oncogênica c-ets-1/antagonistas & inibidores , Animais , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Proteína Proto-Oncogênica c-ets-1/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In spite of impressive success in treating hematologic malignancies, adoptive therapy with chimeric antigen receptor modified T cells (CAR T) has not yet been effective in solid tumors, where identification of suitable tumor-specific antigens remains a major obstacle for CAR T-cell therapy due to the "on target off tumor" toxicity. Protein tyrosine kinase 7 (PTK7) is a member of the Wnt-related pseudokinases and identified as a highly expressed antigen enriched in cancer stem cells (CSCs) from multiple solid tumors, including but not limited to triple-negative breast cancer, non-small-cell lung cancer, and ovarian cancer, suggesting it may serve as a promising tumor-specific target for CAR T-cell therapy. In this study, we constructed three different PTK7-specific CAR (PTK7-CAR1/2/3), each comprising a humanized PTK7-specific single-chain variable fragment (scFv), hinge and transmembrane (TM) regions of the human CD8α molecule, 4-1BB intracellular co-stimulatory domain (BB-ICD), and CD3ζ intracellular domain (CD3ζ-ICD) sequence, and then prepared the CAR T cells by lentivirus-mediated transduction of human activated T cells accordingly, and we sequentially evaluated their antigen-specific recognition and killing activity in vitro and in vivo. T cells transduced with all three PTK7-CAR candidates exhibited antigen-specific cytokine production and potent cytotoxicity against naturally expressing PTK7-positive tumor cells of multiple cancer types without mediating cytotoxicity of a panel of normal primary human cells; meanwhile, in vitro recursive cytotoxicity assays demonstrated that only PTK7-CAR2 modified T cells retained effective through multiple rounds of tumor challenge. Using in vivo xenograft models of lung cancers with different expression levels of PTK7, systemic delivery of PTK7-CAR2 modified T cells significantly prevented tumor growth and prolonged overall survival of mice. Altogether, our results support PTK7 as a therapeutic target suitable for CAR T-cell therapy that could be applied for lung cancers and many other solid cancers with PTK7 overexpression.
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Moléculas de Adesão Celular/imunologia , Imunoterapia Adotiva/métodos , Neoplasias Pulmonares/terapia , Receptores Proteína Tirosina Quinases/imunologia , Receptores de Antígenos Quiméricos/imunologia , Animais , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Citocinas/imunologia , Humanos , Neoplasias Pulmonares/metabolismo , Ativação Linfocitária , Camundongos , Receptores Proteína Tirosina Quinases/metabolismo , Receptores de Antígenos Quiméricos/genética , Especificidade do Receptor de Antígeno de Linfócitos T , Linfócitos T/imunologia , Linfócitos T/transplante , Resultado do Tratamento , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Portal vein velocity (PVV) has shown a reasonable correlation with the presence of portal hypertension in patients with cirrhosis. This study aims to evaluate the value of PVV for diagnosing clinically significant portal hypertension (CSPH) and predicting the risk of variceal hemorrhage (VH) in patients with hepatitis B virus (HBV)-related cirrhosis. MATERIALS AND METHODS: A cohort of 166 consecutive adult patients with HBV-related cirrhosis was recruited in this retrospective study from two high-volume liver centers in China between April 2015 and April 2017. The performance of PVV and other non-invasive parameters for diagnosing CSPH and predicting the risk of VH was studied. RESULTS: PVV demonstrated the best performance for diagnosing CSPH (defined as an HVPG ≥10 mmHg) in patients with HBV-related cirrhosis among the included non-invasive predictors with the area under the receiver operating characteristic curve (AUC), specificity, and sensitivity of 0.745, 50%, and 93.5%, respectively. Other non-invasive markers, including APRI, AAR, LS, FIB-4, and diameter of the portal vein, did not show sufficient performance with the AUCs of 0.565, 0.560, 0.544, 0.529, and 0.474, respectively. With regard to predicting the risk of VH (defined as an HVPG ≥12 mmHg), PPV also exhibited a moderate performance with an AUC of 0.762, which was superior to that of the aforementioned markers. By using two cutoff values of PVV to rule-out (11.65 cm/s) and rule-in (20.20 cm/s) CSPH, 30 (33.7%) patients showed definite results categories, with 23 (76.7%) patients were well classified and 7 (23.3%) were misclassified. Fifty-nine (66.3%) patients were with indeterminate results. By using PVV values of 13.10 cm/s and 21.40 cm/s to rule-out and rule-in HVPG ≥ 12mmHg, 34 (38.2%) patients has definite results, among whom 26 (76.5%) were well classified and 8 (23.5%) were misclassified. And 55 (61.8%) patients required further evaluation. CONCLUSION: PPV is insufficient to serve as a non-invasive parameter for identifying CSPH and predicting the risk of VH in patients with HBV-related cirrhosis.
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Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Hipertensão Portal , Adulto , Hemorragia Gastrointestinal , Vírus da Hepatite B , Humanos , Hipertensão Portal/diagnóstico , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Veia Porta , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the CT and MR features of "inferior vena cava(IVC) reverse-flow" sign and "jet-blood" sign in Budd-Chiari Syndrome (BCS). METHODS: The liver CT and/or MRI plain scan and dynamic enhancement of 107 cases of BCS diagnosed by DSA and/or clinic were collected, including 17 patients with hepatic vein obstruction type, 79 patients with IVC obstruction type, and 11 patients with mixed type. The manifestations of IVC reverse-flow sign and jet-blood sign in the latter two type BCS (90cases) imaging were analyzed. RESULTS: 1) The incidence of IVC reverse-flow sign in the IVC obstruction type and mixed type was 93.3 %(83/90), which was manifested as: The contrast agent was shown below the level of renal veins in the hepatic arterial phase enhancement, while no contrast agent was shown above it at the same time. 2) The incidence of jet-blood sign in membrane-perforated subtype was 100 %(15/15) or 16.7 %(15/90), which was manifested as: The low density/signal dots appeared within full of contrast agent at the superior liver segment IVC on axial slices in arterial phase of CT/MRI enhancement, or the low signal line within agent presented above the IVC membrane on coronal image in equilibrium phase of MR enhancement. 3) Other imaging findings: 75 cases of membrane, 18 cases of membrane calcification, 27 cases of abnormal hepatic vein, 76 cases of abnormal structure of IVC, 18 cases of thrombus/cancer embolus in hepatic vein and/or IVC. There were 65 cases of abnormal liver appearance; 71 cases of abnormal liver enhancement; 21 cases of hepatic vein unsynchronous enhancement. Anastomotic branches among the hepatic veins open with comma sign in 54 cases; dilatation of intraspinal and paravertebral veins, azygos and hemiazygos veins in 90 cases(100 %, 90/90) or 96 cases(89.7 %, 96/107). CONCLUSIONS: The "IVC reverse-flow" sign is a specific CT and MR sign of IVC type and mixed type BCS, and the "jet-blood" sign is a characteristic CT and MR sign of membrane-perforated subtype BCS.
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Síndrome de Budd-Chiari , Síndrome de Budd-Chiari/diagnóstico por imagem , Veias Hepáticas/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Veia Cava Inferior/diagnóstico por imagemRESUMO
Coronary artery bypass graft (CABG) is one of the primary methods of treating coronary heart disease (CHD); however, vein graft restenosis is a major limiting factor of the effectiveness of CABG. Emerging evidence has indicated that miR423 is associated with vascular diseases. Additionally, upregulation of a disintegrin and metalloproteinase with thrombospondin motifs7 (ADAMTS7) contributes to neointima formation by promoting the proliferation and migration of vascular smooth muscle cells and inhibiting the proliferation and migration of endothelial cells. The aim of the present study was to examine the effects of miR423 target, ADAMTS7, on regulating vein graft disease and identify novel biomarkers for use in therapy of vein graft failure (VGF). Aberrant expression of miR423 in plasma of patients with CHD prior to and following CABG confirms that miR423 may be a suitable target for preventing VGF. Furthermore, a dualluciferase reporter gene assay indicated that miR423 directly interacted with ADAMTS7 and suppressed its expression. Ectopic expression of miR423 suppressed ADAMTS7, resulting in decreased proliferation and migration rates of human umbilical vein smooth muscle cells by targeting ADAMTS7, but resulted in increased proliferation and migration of human umbilical vein endothelial cells in vitro. Overexpression of miR423 also enhanced reendothelialization and decreased neointimal formation in a rat vein graft model. In conclusion, the results of the present study demonstrated that the miR423/ADAMTS7 axis may possess potential clinical value for the prevention and treatment of restenosis in patients with CHD following CABG.
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Proteína ADAMTS7/genética , Oclusão de Enxerto Vascular/genética , MicroRNAs/genética , Animais , Movimento Celular , Proliferação de Células , Ponte de Artéria Coronária , Doença das Coronárias/genética , Doença das Coronárias/cirurgia , Regulação para Baixo , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Regulação para CimaRESUMO
The transcription factor AP-2 ß (TFAP2B) serves an important role in kidney development. MicroRNAs (miRNAs) regulate carcinogenic pathways and have gained increasing attention owing to their association with human clear cell renal cell carcinoma (ccRCC) tumorigenesis. However, whether miRNAs could affect renal cell tumorigenesis by regulating TFAP2B expression has not been identified. The aim of this study was to investigate the effects of miRNA on TFAP2B and its potential role in cell growth, invasion and migration. PCR, western blot and dual luciferase reporter assays were performed to analyze the effects of miR-142-5p on TFAP2B. Furthermore, MTT, flow cytometry, wound healing and Transwell migration assays were used to analyze the effect of miR-142-5p on cell proliferation and migration. The results demonstrated that miR-142-5p targeted TFAP2B and downregulated the expression of TFAP2B at the mRNA and protein levels, promoting cell proliferation and migration in two ccRCC cell lines, 786-O and A-498. This phenomenon supported the theory that miR-142-5p may function as an oncogene in ccRCC. The potential clinical significance of miR-142-5p as a biomarker and a therapeutic target provides rationale for further investigation into miR-142-5p-mediated molecular pathways and how these may be associated with ccRCC development.
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The paper presents a novel fetal heart rate (FHR) detecting system which is a fuzzy counter using the auto-correlation and fuzzy mathematic algorithm. This system is able to deal with the increase and decrease phenomena of FHR, caused by the various interference and noises. It has a higher detection level than ever and a better robust system based on the DSP.
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Ecocardiografia Doppler/instrumentação , Monitorização Fetal/instrumentação , Frequência Cardíaca Fetal , Algoritmos , Desenho de Equipamento , Lógica FuzzyRESUMO
By the bioactivity technology of Low-Temperature Preparation of Anatase and Rutile Layers on porous Titanium Substrates, CPTi(Commercially pure titanium Phi4.0 mm x 20 mm) was processed and treated as experiment specimens while CPTi was treated as control specimens. Experiment specimens and control specimens were implanted into the holes (4.0 mm in diameter) in rabbit's right and left tibias respectively. After implantation for predetermined periods of 4,8,12, 16 weeks, the specimens were taken out with bone tissues, and were examined by a press-out tester to evaluate the shearing force between the implant and the bone tissue. It is found that the shearing force between the experiment specimen and the bone is more significantly higher than that between the control specimen and the bone, and the bonding time is shorter, the stabilization time is faster. This study has laid down a good foundation for the titanium metal's innovative applications in clinical orthopaedics.
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Substitutos Ósseos/química , Osso e Ossos , Cristalização , Próteses e Implantes , Titânio/química , Animais , Temperatura Baixa , Teste de Materiais , Dispositivos de Fixação Ortopédica , Coelhos , TíbiaRESUMO
Patients with hepatocellular carcinoma (HCC) exhibit a high incidence of concomitant cirrhosis with leukopenia and/or thrombocytopenia. In the present study, perioperative changes in the white blood cell (WBC) and platelet (PLT) counts and associated complications were investigated to assess the safety of transcatheter arterial chemoembolization (TACE) for HCC patients with preprocedural leukopenia or thrombocytopenia. The records of 1,461 HCC patients who received TACE between January 2012 and December 2013 were retrospectively reviewed. The incidence of complications during the perioperative period and changes in the WBC and PLT counts were recorded. A Chi-squared test was used to evaluate the associations between postoperative infection and preprocedural WBC count and between bleeding at the puncture site and preprocedural PLT count. The WBC count of the majority of the patients increased within 3 days and returned to the preprocedural level within 30 days after TACE. The PLT count decreased within 3 days and returned to the preprocedural level within 30 days after TACE. The major complications were liver decompensation (n=66), puncture site bleeding (n=45), infection (n=33), severe thrombocytopenia (n=8), upper gastrointestinal bleeding (n=6), tumor bleeding (n=4) and agranulocytosis (n=3). A Chi-squared test revealed that postoperative infection was not associated with preprocedural WBC count and puncture site bleeding was not associated with decreased PLT count due to hypersplenism. Therefore, TACE was found to be safe for HCC patients with preprocedural thrombocytopenia or leukopenia due to hypersplenism, with a low incidence of major complications during the perioperative period.
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BACKGROUND: Lung cancer has become the leading cause of death in many regions. Carcinogenesis is caused by the stepwise accumulation of genetic and chromosomal changes. The aim of this study was to investigate the chromosome and gene alterations in the human lung adenocarcinoma cell line OM. METHODS: We used Giemsa banding and multiplex fluorescence in situ hybridization focusing on the human lung adenocarcinoma cell line OM to analyze its chromosome alterations. In addition, the gains and losses in the specific chromosome regions were identified by comparative genomic hybridization (CGH) and the amplifications of cancer-related genes were also detected by polymerase chain reaction (PCR). RESULTS: We identified a large number of chromosomal numerical alterations on all chromosomes except chromosome X and 19. Chromosome 10 is the most frequently involved in translocations with six different interchromosomal translocations. CGH revealed the gains on chromosome regions of 3q25.3-28, 5p13, 12q22-23.24, and the losses on 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p13.31-13.33 and 17p13.1-13.3. And PCR showed the amplification of genes: Membrane metalloendopeptidase (MME), sucrase-isomaltase (SI), butyrylcholinesterase (BCHE), and kininogen (KNG). CONCLUSIONS: The lung adenocarcinoma cell line OM exhibited multiple complex karyotypes, and chromosome 10 was frequently involved in chromosomal translocation, which may play key roles in tumorigenesis. We speculated that the oncogenes may be located at 3q25.3-28, 5p13, 12q22-23.24, while tumor suppressor genes may exist in 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p13.31-13.33, and 17p13.1-13.3. Moreover, at least four genes (MME, SI, BCHE, and KNG) may be involved in the human lung adenocarcinoma cell line OM.