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PURPOSE: To explore the value of virtual surgery and 3D printing model combined with guide plate in treatment of mandibular condylar neck fracture. METHODS: Seven patients with mandibular condylar neck fracture were scanned by CT for original data. The data were exported in DICOM format. A three-dimensional model was reconstructed using software, the fracture was reduced by virtual surgery, and the 3D model was printed by a 3D printer. A prebent titanium plate was used to fabricate the guide plate, which was used for reduction and fixation of the fracture block during surgery. RESULTS: All the postoperative incisions revealed no signs of infection, the wounds were hidden and beautiful. The implanted titanium plates were highly compatible with the reduced fracture segments. The patients were followed up for 6 months after surgery, the condylar fracture healed well and there was no obvious displacement. The patient developed no mandibular deviation with a stable occlusion, and no occlusal pain was reported. No obvious temporomandibular joint disorder was present. CONCLUSIONS: Virtual surgery and 3D printing model combined with guide plate can ensure an accurate reduction of condylar neck fracture and simplify the operation process, which can be used as an accurate, efficient and predictable auxiliary method.
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Fraturas Mandibulares , Procedimentos de Cirurgia Plástica , Humanos , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/cirurgia , Fixação Interna de Fraturas/métodos , Titânio , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/cirurgia , Placas ÓsseasRESUMO
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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Inflammation status are especially for tumor growth, and microRNAs (miRNAs) confirmed to participate in cancer occurrence and progression. However, the role of miR-483-5p and the relation with inflammation have not been elucidated in renal cell cancer (RCC). In this study, we intended to explore miR-483-5p expression and the relationship of inflammation status in clear cell renal cell cancer (ccRCC). Using microarray and qRT-PCR (Quantitative Real-time Polymerase Chain Reaction), we investigated the miR-483-5p expression in plasma and ccRCC cancer tissues. Then, we analyzed the correlation of miR-483-5p with clinicopathological parameters and inflammation status in ccRCC. Receiver operator characteristic (ROC) curves analysis was used to analyze the discrimination efficiency of miR-483-5p. in vitro experiments explored the biological role of miR-483-5p in renal cancer cells. miR-483-5p expression was upregulated in plasma of 5 patients with microarray and 12 patients with qRT-PCR in ccRCC at day 7 postoperatively. In addition, low expression of miR-483-5p was found in 58 ccRCC cancer tissues when compared with non-cancerous tissues. miR-483-5p could sufficiently discriminate ccRCC with the area under the curve (AUC) of 0.739 (P < .0001) from normal tissues. Higher expression of miR-483-5p was positively related to lower tumor stage and higher relative expression of miR-483-5p was inversely related to neutrophil-to-lymphocyte ratio (NLR) (P = .03) and lymphocyte-to-monocyte ratio (LMR) (P = .026). Overexpression of miR-483-5p lead to reverse epithelial-mesenchymal transition (EMT) process, restrain cell proliferation and metastasis of renal cancer cells. Our findings suggest that miR-483-5p expression is negatively correlation with inflammation status and may be a potential plasma biomarker for ccRCC.
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Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Regulação para Baixo/genética , Inflamação/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , MicroRNAs/genética , Carcinoma de Células Renais/sangue , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/sangue , MicroRNAs/sangue , Estadiamento de Neoplasias , Nefrectomia , Regulação para Cima/genéticaRESUMO
ABSTRACT Background: Previous functional magnetic resonance imaging (fMRI) studies showed inconsistent results for comparison between bipolar disorder (BD) and healthy controls (HC). Methods: An anatomic likelihood estimation (ALE) meta-analysis was used to explore the key regions of brain pathology in BD with different current mood states. Results: Depressed BD patients showed reduced regional homogeneity (ReHo) in the left claustrum and the left middle frontal gyrus (MFG), compared to HC. BD patients with mixed mood status showed decreased fractional amplitude of low frequency fluctuations (fALFF) in the right cerebellar tonsil, the bilateral MFG and the right superior frontal gyrus, compared to HC. Additionally, BD patients with mixed mood status showed increased fALFF in the right inferior occipital gyrus, the right culmen and the left lentiform nucleus, compared to HC. BD patients with mixed mood status showed decreased functional connectivity (FC) in the bilateral cerebellar tonsil, compared to HC. Conclusion: In the present study, key regions undergoing functional deficits in BD patients with different current mood states were obtained with the ALE meta-analysis. In addition, deficits in these regions in fMRI studies might work as biomarkers for early diagnosis of BD.
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Although serum bile acids and total cholesterol (TC) are closely related to liver cirrhosis, the potential diagnostic value of total bile acid-to-cholesterol ratio (TBA/TC) for liver fibrosis is unclear. The present study aimed to evaluate the value of TBA/TC in the diagnosis of cirrhosis and the relationship between TBA/TC and significant liver fibrosis in chronic hepatitis B virus (HBV) infected patients without cholestasis.667 patients with alkaline phosphatase (ALP) ≤ 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) ≤ 3 ULN were rigorously included in this cross-sectional study. Liver biopsy was performed in 32 patients and METAVIR scoring system was used to evaluate liver fibrosis stage. Liver ultrasound elastography was performed in 138 patients, significant fibrosis was defined as fibrosis ≥ F2. Multiple logistic regression as well as receiver operating characteristic (ROC) curves analyses were performed.Compared to patients with non-cirrhosis, TBA and TBA/TC were significantly higher in cirrhosis while TC was significantly lower (all Pâ<â.001). In multivariate analysis, TBA/TC was also independently associated with cirrhosis [odds ratio (OR) = 1.102, 95% confidence interval (CI): 1.085-1.166]. The area under the curve (AUC) of TBA/TC (0.87) was almost equivalent to the aspartate aminotransferase to platelet ratio index (APRI, AUCâ=â0.84) and fibrosis 4 score (FIB-4, AUCâ=â0.80), and the optimal cut-off value for TBA/TC to diagnose cirrhosis was 2.70. Among the patients performed liver biopsy, TBA/TC were significantly higher both in significant fibrosis and cirrhosis as well as significantly correlated with fibrosis stage (all Pâ<â.001). Furthermore, In patients performed liver ultrasound elastography, TBA/TC was also independently associated with significant fibrosis (ORâ=â1.040, 95% CI: 1.001-1.078).Assessment of TBA/TC could serve as an additional marker of significant liver fibrosis and cirrhosis in non-cholestatic chronic HBV infection.
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Ácidos e Sais Biliares/sangue , Colesterol/sangue , Hepatite B Crônica/complicações , Cirrose Hepática/etiologia , Adulto , Biomarcadores , Biópsia , Estudos Transversais , Técnicas de Imagem por Elasticidade , Feminino , Hepatite B Crônica/sangue , Humanos , Cirrose Hepática/sangue , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de DoençaRESUMO
BACKGROUND: This study systematically reviews the data for transcatheter arterial chemoembolization (TACE) alone or combined TACE and cryoablation therapy of hepatocellular carcinoma, aiming to provide clinical choice references for treatment of cancer. METHODS: Electronic databases (PubMed, EMBASE, China National Knowledge Infrastructure, and Google Scholar) were systematically searched to include relevant studies published in English and Chinese between Jan 1, 2000, to July 31, 2017. The analysis was conducted in RevMan 5.3 based on random effects models. RESULTS: Nineteen trials (nâ=â1427) were included. Combined TACE and cryoablation therapy had higher survival rate (1-year survival [RR 1.37; 95%-CI 1.26,1.49], 2-year survival [RR 1.50; 95%-CI 1.25,1.79], 3-year survival [RR 1.67; 95%-CI 1.16,2.40]), complete necrosis [RR 2.53; 95%-CI 2.07,3.10] and tumor control [RR 1.57; 95%-CI 1.40,1.75], which is more favorable for long-term efficacy of non-surgical hepatocellular carcinoma. Tumor recurrence of control group was above combination therapy [RR 0.27; 95%-CI 0.17, 0.43]. Compared with transcatheter arterial chemoembolization, effect of combination therapy occurred mainly in the survival, complete necrosis, tumor control, and recurrence. Taking combination therapy was generally more effective than taking TACE only. CONCLUSION: Compared with TACE only used to treat cancer, combination therapy had the best effect profile in general, and it had better survival in HCC when taking an integrated approach. The prognosis of treatments based on combination therapy is modulated by cryoablation.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Criocirurgia/métodos , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Taxa de SobrevidaRESUMO
Aldosterone (Aldo), a pivotal hormone that is ubiquitously expressed in systemic tissues of mammals, is a crucial factor in the pathogenesis of cardiac disease. Accumulating evidence suggests that disturbances in cell energy metabolism are involved in increasing aldosterone levels. However, the precise mechanism underlying the impact of cardiac metabolic remodeling underlying aldosterone stimulation remains limited. In this work, we evaluated the underlying effect of aldosterone on regulating cardiac metabolism remodeling in a canine model. Fifteen beagle dogs were divided into a control group (n = 5), Aldo group (n = 5), and a group treated with spironolactone (SP), a mineralocorticoid receptor antagonist (n = 5), for 4 weeks. Blood pressure, electrocardiogram and respiratory parameters, H&E, Masson staining, ultrastructural changes, the adenosine triphosphate (ATP) and free fatty acid (FFA) levels of ventricular tissues, the level of mRNA, and the protein expression of key metabolic factors and regulators were assessed. The Sirt1/AMPK signaling pathway was significantly inhibited in the canine model of aldosterone stimulation, resulting in a reduction of the key downstream metabolic factors involved in glucose and fatty acid oxidation. The dysregulation of expression of key factors in glycogen metabolism led to glycogen deposition, an increase in FFA levels, a reduction in ATP levels, apoptosis, inflammatory cell infiltration, and mitochondrial damage in the ventricular myocardium. These effects were significantly restored by spironolactone. Aldosterone stimulation induced cardiac metabolic remodeling in ventricular cardiomyocytes possibly through the Sirt1/AMPK signaling pathway, implying that this pathway may provide a novel therapeutic target for cardiac metabolic remodeling.
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Proteínas Quinases Ativadas por AMP/metabolismo , Aldosterona/metabolismo , Ventrículos do Coração/metabolismo , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Sirtuína 1/metabolismo , Espironolactona/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Aldosterona/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Cães , Eletrocardiografia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Transdução de SinaisRESUMO
Deltoid ligament reconstruction following type B ankle fractures continues to generate a vivid discussion amongst trauma surgeons. There is a difference of opinion as to whether operative or non operative treatment should prevail. We therefore conducted a prospective comparative cohort study to determine whether it is necessary to routinely repair the injured deltoid ligaments. 41 Type B ankle joint fracture patients were enrolled, all the patients were associated with deltoid ligament ruptures and lateral/posterior-lateral dislocation of talus. After fixation of the lateral malleolus fracture, 12 patients were treated by superficial deltoid ligaments repairing, 16 patients with deep components augmentation, 13 patients had no direct surgical intervention. In the deep components group, the planter and the dorsi flexion was 3.2° (0-10°) and 8.8° (0-15°) less than the normal side. In the superficial components group, plantar and dorsi flexion was 0.8° (0-5°) and 4.2° (0-15°) less than the normal side. In the non-repairing group, the plantar and dorsi flexion was 2.4° (0-10°) and 5.6° (0-20°) less than the normal side. Overall, no significant statistical difference was observed comparing the 3 groups. In addition, no statistically significant inter-group differences were evident in terms of measurement of the ankle medial clear space and the clinical and functional outcomes recorded. In conclusion, the results of this study do not support routine exposure and repairing of the injured deltoid ligaments.
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Fraturas do Tornozelo/cirurgia , Traumatismos do Tornozelo/cirurgia , Articulação do Tornozelo/cirurgia , Músculo Deltoide/lesões , Fixação Interna de Fraturas/métodos , Ligamentos Articulares/lesões , Adolescente , Adulto , Fraturas do Tornozelo/fisiopatologia , Traumatismos do Tornozelo/fisiopatologia , Articulação do Tornozelo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recuperação de Função Fisiológica/fisiologia , Resultado do Tratamento , Procedimentos Desnecessários , Adulto JovemRESUMO
The aberrant expression of long noncoding RNAs (lncRNAs) has been reported frequently in specific cancers, including high-grade serous ovarian cancer (HGSOC). The purpose of the present study was to explore the clinical significance and underlying mechanisms of a significantly dysregulated lncRNA (NEAT1) in HGSOC. Our results showed that elevated NEAT1 expression in human HGSOC specimens correlated with a poor prognosis. Functional experiments demonstrated that knockdown of NEAT1 significantly prohibited ovarian cancer cell proliferation and invasion in vitro and restrained tumor growth in vivo. LIN28B was identified by bioinformatics analysis along with experimental evidence as a direct actor that enhanced NEAT1 stability. A rescue functional assay confirmed that the LIN28B/NEAT1 axis contributed to oncogenic functions in ovarian cancer cells. Moreover, gene expression profile data and dual luciferase reporter assay results demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for miR-506 to promote cell proliferation and migration. Taken together, our results showed that NEAT1, stabilized by LIN28B, promoted HGSOC progression by sponging miR-506. Thus, NEAT1 can be regarded as a vital diagnostic biomarker for HGSOC and a therapeutic target.
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Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , Neoplasias Ovarianas/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Apoptose/genética , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Regulação para Cima/genéticaRESUMO
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) is the major antigen of the CD66 cluster of granulocyte differentiation antigens. The present study aimed to assess the biological function of CEACAM-1 on the growth of human colorectal cancer (CRC) cells in vitro. Treatment of cultured CRC HCT-8 cells with CEACAM-1-specific siRNA successfully downregulated CEACAM-1 expression by 61% compared with control cells. The effects of CEACAM-1 downregulation on HCT-8 cell proliferation and apoptosis were then assessed via Cell Counting kit-8 assay and flow cytometry, respectively. The results demonstrated that siRNA-induced CEACAM-1 downregulation significantly inhibited proliferation and increased apoptosis, but had no significant effect on cell cycle progression in HCT-8 cells. Together, these results suggest that CEACAM-1 activity is critical to CRC growth, and thus, CEACAM-1 may be a promising therapeutic target for the treatment of CRC.
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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.
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Adenocarcinoma/genética , Aberrações Cromossômicas , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão , Linhagem Celular Tumoral , Bandeamento Cromossômico , Duplicação Cromossômica , Hibridização Genômica Comparativa , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Reação em Cadeia da Polimerase , Translocação GenéticaRESUMO
Mammalian orthoreoviruses (MRVs) are widespread and infect virtually all mammals. We report here the first case of a natural mutant and reassortant serotype 3 reovirus from mink in China, known as MRV3 SD-14. Whole-genome sequence analysis showed that the MRV3 SD-14 may have resulted from a reassortment involving MRVs that infected swine, humans and mink. Interestingly, the S1 segment, which encodes the viral attachment protein σ1, which influences viral virulence and cell tropism in the host, had a stop codon mutation at amino acid 246. Surveillance of the virulence and evolution of MRVs in humans and other animals deserves more attention.
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Genoma Viral , Orthoreovirus Mamífero 3/classificação , Orthoreovirus Mamífero 3/genética , Vison/virologia , RNA Viral/genética , Vírus Reordenados/classificação , Vírus Reordenados/genética , Animais , China , Códon sem Sentido , Humanos , Dados de Sequência Molecular , Análise de Sequência de DNA , Suínos , Proteínas do Envelope Viral/genéticaRESUMO
OBJECTIVE: This study aims to explore the effect of Notch signaling depression on the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis of RAW264.7 cells. METHODS: Mice RAW264.7 cells were cultured and differentiated into osteoclasts with the induction of RANKL. The expressions of Notch1, Notch2, Deltal, Jagged1, Hes1, tartrate-resistant acid phosphatase (TRAP), and Cathepsin K genes during osteoclastogenesis were analyzed using real-time polymerase chain reaction. Osteoclast formation was analyzed using TRAP assay with suppression of Notch receptors by a selective γ-secretase inhibitor (GSI). RESULTS: Notch1, Notch2, Delta1, Jagged1, and Hes1 expressions in RAW264.7 cells were upregulated following 50 ng · mL-RANKL stimulation for 3 d, concomitant with the expression of the osteoclast differentiation markers TRAP and Cathepsin K. Notch2 and Jagged1 had the most remarkable increase in the Notch family members. GSI inhibited RANKL-induced osteoclastogenesis of RAW264.7 cells and Hes1 expression dose-dependently. CONCLUSION: Notch signaling activation may promote RANKL-induced osteoclastogenesis of RAW264.7 cells.
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Ligante RANK , Animais , Catepsina K , Diferenciação Celular , Técnicas In Vitro , Camundongos , Osteoclastos , OsteogêneseRESUMO
BACKGROUND: With the development of surgical techniques and biomedical material, increasing synthetic materials are applied to the chest wall reconstruction, such as autologous rib, muscle flap, bovine pericardium and sheet metal. AIM: To detect the safety and efficiency of synthetic material Polydioxanone (PDO) in chest wall reconstruction. MATERIALS AND METHODS: Healthy adult mongrel dogs operated with PDO, and then some clinical data were collected. RESULTS: Here we showed that PDO mesh could close down the function of chest wall defect, and PDO mesh could be degraded gradually and forms a fibrous layer with the surrounding tissues. Our data further demonstrated PDO mesh leads to slight lung adhesion with a small shrinkage. CONCLUSIONS: These findings thus provide the first evidence that the feasibility of PDO mesh in chest wall reconstruction in dogs.
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Materiais Biocompatíveis , Procedimentos de Cirurgia Plástica/instrumentação , Polidioxanona , Telas Cirúrgicas , Procedimentos Cirúrgicos Torácicos/instrumentação , Parede Torácica/cirurgia , Animais , Cães , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Masculino , Modelos Animais , Polidioxanona/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Telas Cirúrgicas/efeitos adversos , Procedimentos Cirúrgicos Torácicos/efeitos adversos , Fatores de Tempo , Aderências Teciduais , CicatrizaçãoRESUMO
The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection.
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Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Pericárdio/metabolismo , Animais , Fibroblastos/metabolismo , Coração/fisiologia , Traumatismos Cardíacos/metabolismo , Homeostase , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos , Modelos Biológicos , Modelos Genéticos , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Neovascularização Patológica , Resultado do TratamentoAssuntos
Cálculos/complicações , Perfuração Esofágica/etiologia , Adulto , Cálculos/diagnóstico por imagem , Diospyros/efeitos adversos , Doenças do Esôfago/complicações , Doenças do Esôfago/diagnóstico por imagem , Perfuração Esofágica/diagnóstico por imagem , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Alternative mRNA splicing is an important mechanism for regulation of gene expression. Altered mRNA splicing occurs in association with several types of cancer, and a small number of disease-associated changes in splicing have been reported in heart disease. However, genome-wide approaches have not been used to study splicing changes in heart disease. We hypothesized that mRNA splicing is different in diseased hearts compared with control hearts. METHODS AND RESULTS: We used the Affymetrix Exon array to globally evaluate mRNA splicing in left ventricular myocardial RNA from controls (n=15) and patients with ischemic cardiomyopathy (n=15). We observed a broad and significant decrease in mRNA splicing efficiency in heart failure, which affected some introns to a greater extent than others. The profile of mRNA splicing separately clustered ischemic cardiomyopathy and control samples, suggesting distinct changes in mRNA splicing between groups. Reverse transcription-polymerase chain reaction validated 9 previously unreported alternative splicing events. Furthermore, we demonstrated that splicing of 4 key sarcomere genes, cardiac troponin T (TNNT2), cardiac troponin I (TNNI3), myosin heavy chain 7 (MYH7), and filamin C, gamma (FLNC), was significantly altered in ischemic cardiomyopathy and in dilated cardiomyopathy and aortic stenosis. In aortic stenosis samples, these differences preceded the onset of heart failure. Remarkably, the ratio of minor to major splice variants of TNNT2, MYH7, and FLNC classified independent test samples as control or disease with >98% accuracy. CONCLUSIONS: Our data indicate that mRNA splicing is broadly altered in human heart disease and that patterns of aberrant RNA splicing accurately assign samples to control or disease classes.
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Insuficiência Cardíaca/genética , Proteínas dos Microfilamentos/genética , Splicing de RNA , Sarcômeros/genética , Estenose da Valva Aórtica/genética , Cardiomiopatia Dilatada/genética , Biologia Computacional , Proteínas Contráteis/genética , Éxons , Filaminas , Ventrículos do Coração/metabolismo , Humanos , Isquemia Miocárdica/genética , Cadeias Pesadas de Miosina/genética , Troponina I/genética , Troponina T/genéticaRESUMO
Polybrominated diphenyl ethers (PBDEs) are widely used as flame-retardant additives. But the application of PBDEs has been challenged due to their toxicity, especially neurotoxicity. In this study, we investigated the effects of decabrominated diphenyl ether (PBDE 209), the major PBDEs product, on voltage-gated sodium channels (VGSCs) in primary cultured rat hippocampal neurons. Employing the whole-cell patch-clamp technique, we found that PBDE 209 could irreversibly decrease voltage-gated sodium channel currents (I(Na)) in a very low dose and in a concentration-dependent manner. We had systematically explored the effects of PBDE 209 on I(Na) and found that PBDE 209 could shift the activation and inactivation of I(Na) toward hyperpolarizing direction, slow down the recovery from inactivation of I(Na), and decrease the fraction of activated sodium channels. These results suggested that PBDE 209 could affect VGSCs, which may lead to changes in electrical activities and contribute to neurotoxicological damages. We also showed that ascorbic acid, as an antioxidant, was able to mitigate the inhibitory effects of PBDE 209 on VGSCs, which suggested that PBDE 209 might inhibit I(Na) through peroxidation. Our findings provide new insights into the mechanism for the neurological symptoms caused by PBDE 209.
Assuntos
Éteres Difenil Halogenados/toxicidade , Hipocampo/efeitos dos fármacos , Ativação do Canal Iônico , Neurônios/efeitos dos fármacos , Canais de Sódio/efeitos dos fármacos , Animais , Hipocampo/citologia , Hipocampo/metabolismo , Neurônios/metabolismo , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Canais de Sódio/metabolismo , Técnicas de Cultura de TecidosRESUMO
OBJECTIVES: The study aim was to evaluate the safety and feasibility of radiofrequency ablation for the surgical treatment of permanent atrial fibrillation in patients with degenerative mitral valve disease. DESIGN: From August 2000 to August 2003, 40 consecutive patients (mean age 69.0 +/- 9.3 years) with permanent atrial fibrillation and degenerative mitral valve disease underwent surgical radiofrequency ablation in conjunction with 22 mitral valve repairs and 18 mitral valve replacements. The mean duration of chronic AF was 5.1 +/- 3.4 years. The completeness of follow-up was 100%. The mean follow-up time was 4.6 +/- 2.0 years (range 0 to 7.8 years). RESULTS: Thirty-day mortality was 2.5% (1 patient), the cause of death was cardiac failure. Cardiac failure and temporary A-V block were the most common postoperative complications. Both occurred in 10% (4 patients). No complication was related to the ablation procedure. At discharge, 65% (26/40) of the patients were in sinus rhythm. Overall incidence of sinus rhythm at the end of the follow-up was 56.4% (22/39).The 1-, 3- and 5-year survival was 97.5%, 91.8% and 85.9%, respectively. CONCLUSION: Mitral valve surgery combined with radiofrequency ablation is a safe and effective procedure in patients with permanent atrial fibrillation and degenerative mitral valve disease. The result is encouraging in restoring sinus rhythm, and an excellent postoperative survival rate can be achieved.