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BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.
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Broncoscopia , Fenômenos Eletromagnéticos , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Valor Preditivo dos Testes , Humanos , Broncoscopia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Nódulos Pulmonares Múltiplos/patologia , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/cirurgia , Estudos Retrospectivos , Carga Tumoral , Adulto , Nódulo Pulmonar Solitário/patologia , Nódulo Pulmonar Solitário/diagnóstico , Nódulo Pulmonar Solitário/cirurgia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Reprodutibilidade dos Testes , Idoso de 80 Anos ou mais , Biópsia Guiada por Imagem/métodosRESUMO
Background: Drug resistance is a major contributing factor to chemotherapy failure in hepatocellular carcinoma (HCC) patients. However, the exact mechanism underlying the chemoresistance of HCC remains unknown. Methods: HepG2 cells were incubated with different concentrations of 5-fluorouracil (5-FU), and the Cell Counting Kit-8 assay was used to test the cell survival rate. The expression level of structural maintenance of chromosome 4 (SMC4) in drug-resistant cells was analyzed by real-time quantitative polymerase chain reaction (PCR) and western blotting. To assess autophagy, immunofluorescence was applied to detect the light chain 3 beta (LC3B) level in HepG2/5-FU cells. To further study the upstream regulation of miR (microRNA)-219/SMC4, a gene chip assay was performed. A luciferase reporter assay was used to determine whether long non-coding RNA-XIST (lncRNA-XIST) functions as a competitive endogenous RNA (ceRNA) for miR-219. Cellular proliferation was evaluated using MTT [3-(4,5)-dimethylthiahiazo (-z-y1)-2,5-di-phenytetrazoliumromide] and colony formation assays, wound healing and invasion assays were performed to study the invasion and migration ability of the cells, and flow cytometry assays were carried out to evaluate cell apoptosis. Results: In the present study, we established a drug-resistant hepatoma cell line named HepG2/5-FU. We confirmed that SMC4 may play an important role in hepatoma cell autophagy and could promote autophagy to increase the drug resistance of hepatoma cells. We also demonstrated that lncRNA-XIST may competitively bind to miR-219 by acting as a miRNA sponge, thereby preventing miR-219 from effectively reducing the expression of SMC4 and further affecting the autophagy and drug resistance of hepatoma cells via the adenosine 5'-monophosphate (AMP)-activated protein kinase/mechanistic target of rapamycin (AMPK/mTOR) pathway. Conclusions: Our study suggests that SMC4 may be a potential marker of a poor HCC response to chemotherapy and a novel therapeutic target for HCC chemotherapy.
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Atrial fibrillation (AF) is the most common cardiovascular disease (CVD), and most existing algorithms are usually designed for the diagnosis (i.e., feature classification) or prediction of AF. Artificial intelligence (AI) algorithms integrate the diagnosis of AF electrocardiogram (ECG) and predict the possibility that AF will occur in the future. In this paper, we utilized the MIT-BIH AF Database (AFDB), which is composed of data from normal people and patients with AF and onset characteristics, and the AFPDB database (i.e., PAF Prediction Challenge Database), which consists of data from patients with Paroxysmal AF (PAF; the records contain the ECG preceding an episode of PAF), and subjects who do not have documented AF. We extracted the respective characteristics of the databases and used them in modeling diagnosis and prediction. In the aspect of model construction, we regarded diagnosis and prediction as two classification problems, adopted the traditional support vector machine (SVM) algorithm, and combined them. The improved quantum particle swarm optimization support vector machine (IQPSO-SVM) algorithm was used to speed the training time. During the verification process, the clinical FZU-FPH database created by Fuzhou University and Fujian Provincial Hospital was used for hybrid model testing. The data were obtained from the Holter monitor of the hospital and encrypted. We proposed an algorithm for transforming the PDF ECG waveform images of hospital examination reports into digital data. For the diagnosis model and prediction model trained using the training set of the AFDB and AFPDB databases, the sensitivity, specificity, and accuracy measures were 99.2% and 99.2%, 99.2% and 93.3%, and 91.7% and 92.5% for the test set of the AFDB and AFPDB databases, respectively. Moreover, the sensitivity, specificity, and accuracy were 94.2%, 79.7%, and 87.0%, respectively, when tested using the FZU-FPH database with 138 samples of the ECG composed of two labels. The composite classification and prediction model using a new water-fall ensemble method had a total accuracy of approximately 91% for the test set of the FZU-FPH database with 80 samples with 120 segments of ECG with three labels.
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Fibrilação Atrial , Máquina de Vetores de Suporte , Algoritmos , Inteligência Artificial , Fibrilação Atrial/diagnóstico , Eletrocardiografia , HumanosRESUMO
BACKGROUND: Preoperative prognostic biomarkers to guide individualized therapy are still in demand in esophageal squamous cell cancer (ESCC). Some studies reported that radiomic analysis based on CT images has been successfully performed to predict individual survival in EC. The aim of this study was to assess whether combining radiomics features from primary tumor and regional lymph nodes predicts overall survival (OS) better than using single-region features only, and to investigate the incremental value of the dual-region radiomics signature. METHODS: In this retrospective study, three radiomics signatures were built from preoperative enhanced CT in a training cohort (n = 200) using LASSO Cox model. Associations between each signature and survival was assessed on a validation cohort (n = 107). Prediction accuracy for the three signatures was compared. By constructing a clinical nomogram and a radiomics-clinical nomogram, incremental prognostic value of the radiomics signature over clinicopathological factors in OS prediction was assessed in terms of discrimination, calibration, reclassification and clinical usefulness. RESULTS: The dual-region radiomic signature was an independent factor, significantly associated with OS (HR: 1.869, 95% CI: 1.347, 2.592, P = 1.82e-04), which achieved better OS (C-index: 0.611) prediction either than the single-region signature (C-index:0.594-0.604). The resulted dual-region radiomics-clinical nomogram achieved the best discriminative ability in OS prediction (C-index:0.700). Compared with the clinical nomogram, the radiomics-clinical nomogram improved the calibration and classification accuracy for OS prediction with a total net reclassification improvement (NRI) of 26.9% (P=0.008) and integrated discrimination improvement (IDI) of 6.8% (P<0.001). CONCLUSION: The dual-region radiomic signature is an independent prognostic marker and outperforms single-region signature in OS for ESCC patients. Integrating the dual-region radiomics signature and clinicopathological factors improves OS prediction.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Humanos , Linfonodos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is occasionally observed with synchronous multiple tumor lesions. Our study is aiming to define the clinical and prognostic features of this pathological subtype. METHODS: This study included a large cohort of 1126 ESCC patients received esophagectomy with systemic lymph-node dissection between 2003 and 2013 in Sun Yat-sen University Cancer Center. The characteristics and prognostic significance of ESCC with multiple lesions were analyzed. The propensity score matching was performed to balance the baseline clinical characteristics. RESULTS: A total of 103 patients (9.1%) with 216 synchronous multiple lesions were identified from postoperative gross samples. Among them, 94 patients had two lesions, and 8 patients had three lesions, while only one patient had four lesions. The consistency of pT stages and histological grade among tumor lesions from the same gross sample were 19.4% (20/103) and 37.9% (39/103), respectively. Additionally, the tumor sites, sizes, and even the pathological subtypes can be variant in one patient. The preoperative upper gastrointestinal endoscopy could only identified 80.1% of the multiple tumor lesions. The male gender (P = 0.012), positive personal cancer history (P < 0.001), and higher pN stages (P < 0.001) were independent risk factors for synchronous multiple lesions. Patients with multiple lesions showed significantly lower survival rate (P = 0.002), and the multiple-lesion was an independently adverse prognostic factor in operable ESCC (P = 0.002). CONCLUSION: ESCC with multiple lesions had unique clinical features and should not be simply treated as the one-lesion ESCC. Due to its worse prognostic impact, advanced multidisciplinary therapies should be considered for patients with multiple esophageal tumor lesions.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Masculino , Estadiamento de Neoplasias , PrognósticoRESUMO
OBJECTIVES: The ligation of thoracic duct interrupts the normal lymphatic circulation. Whether the ligation of thoracic duct would affect tumor recurrence and patient survival is unclear. METHODS: The correlations between prophylactic thoracic duct ligation (PLG) and prognosis were examined in patients with esophageal squamous cell carcinoma. Patients who received Ivor Lewis or McKeown esophagectomy with systemic lymph node dissection and R0 resection between 2003 and 2013 in Sun Yat-sen University Cancer Center were included in the study. RESULTS: A total number of 473 and 462 were included in the PLG group and non-prophylactic thoracic duct ligation (NPLG) group, respectively. The PLG group had a lower 5-year survival rate (48.2% vs 61.6%, P < .001). After a 1:1 propensity score matching, 874 cases (437 pairs) were included and the survival analysis showed that PLG was associated with worse 5-year cumulative survival of 48.6% vs 61.6% in those patients without ligation (P < .001). The multivariate analysis revealed that PLG was an independent factor for poor prognosis after esophagectomy (hazard ratio, HR = 1.56; 95% confidence interval, 95% CI, 1.26-1.93, P < .001). Additionally, PLG was associated with regional lymph node relapse (P = .015). CONCLUSIONS: PLG should not be performed routinely if no sign of thoracic duct rupture or tumor invasion were identified.
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Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Recidiva Local de Neoplasia/patologia , Ducto Torácico/cirurgia , Quilotórax/epidemiologia , Quilotórax/etiologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagectomia/métodos , Esofagectomia/estatística & dados numéricos , Feminino , Humanos , Ligadura/métodos , Ligadura/estatística & dados numéricos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/estatística & dados numéricos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Cervical cancer pathogenesis is regulated by numerous factors, including microRNAs. MicroRNA 1246 (miR-1246) has been shown to serve a role in cervical cancer tumorigenesis. However, the mechanisms through which miR-1246 exerts its oncogenic effects are largely unknown. The aim of the current study was to evaluate the effects of lentivirus-mediated miR-1246 knockdown on the biological characteristics and behavior of cervical cancer cells, and to identify the downstream signaling pathways affected by miR-1246 knockdown. Short hairpins inhibiting miR-1246 were synthesized and cloned into a recombinant lentiviral vector (LV-miR-1246-Inh), which was then used to infect SiHa cervical cancer cells. The effects of LV-miR-1246-Inh infection on cell invasion, proliferation and apoptosis were evaluated by Transwell assay, Cell Counting Kit-8 assay and flow cytometry, respectively. Thrombospondin-2 (THBS2), matrix metalloproteinase 2 (MMP2), MMP9 and extracellular matrix (ECM) component expression levels were evaluated, and the growth of xenograft tumors formed following injection of SiHa cells with knockdown of miR-1246 was assessed. miR-1246 downregulation in SiHa cells decreased proliferation, induced apoptosis and upregulated THBS2 expression. Furthermore, MMP2 and MMP9 levels were downregulated, whereas components of the ECM were upregulated subsequent to miR-1246 knockdown, indicating that this miRNA regulates cervical cancer cell pathogenesis via the THBS2/MMP/ECM pathway. Notably, SiHa cells with miR-1246 downregulation had a markedly decreased ability to form tumors in vivo. These results suggest that miR-1246 functions during cervical cancer pathogenesis and tumor formation via the THBS2/MMP/ECM signaling pathway. These findings support the future use of miR-1246 suppression in the treatment of cervical cancer.
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Successful seed germination depends on the rapid repair of cell membrane damaged by dry storage. However, little is known about the reorganization of lipids during this process. In this study, the changes of intracellular redox environment, cell membrane integrity, lipid composition, and expression of genes related to phospholipid metabolism were assessed during imbibition of Brassica napus seeds. A total number of 443 lipids belonging to 7 categories were detected by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). In the 24 h-imbibed seeds, the relative content of triacylglycerol was lower than in dry seeds, while the relative content of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), especially PC (36:2, number of carbons in the acyl chains: number of double bonds), PC (36:3), and PE (36:3) were higher than those in dry seeds. Meanwhile, the content and unsaturation levels of phospholipids increased, indicating membrane lipids remodeling during seed imbibition. The plasma membrane integrity, which was measured by the relative electrolyte leakage (REL) of the membrane and FM4-64 fluorescent dye, was improved upon imbibition, confirming that cell membrane was repaired after 24â¯h-imbibition. The reduction of H2O2 content, redox potential, and malondialdehyde (MDA) content indicated that the degree of membrane lipid peroxidation was significantly decreased upon imbibition. Gene expression analysis showed that the differential expression of genes for key enzymes occurred in the plateau phase of the imbibition curve, i.e. after 8â¯h-to 24â¯h-imbibition. Moreover, the differential expression of genes such as those encoding phospholipase C (PLC), phospholipase D (PLD), triacylglycerol lipase (TAG lipase), choline/ethanolamine phosphotransferase (CEPT), and phosphatidylserine synthase (PTDSS2) during imbibition indicated that membrane lipid remodeling was related to complex metabolic pathways, among which the degradation of triacylglycerol and the synthesis of phospholipids using diacylglycerol might play an important role during membrane remodeling.
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Brassica napus/metabolismo , Lipídeos de Membrana/metabolismo , Fosfolipídeos/metabolismo , Brassica napus/genética , Brassica napus/crescimento & desenvolvimento , Membrana Celular/metabolismo , Corantes Fluorescentes , Genes de Plantas , Germinação/genética , Germinação/fisiologia , Lipídeos de Membrana/química , Fosfolipídeos/química , Compostos de Piridínio , Compostos de Amônio Quaternário , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , TranscriptomaRESUMO
PURPOSE: The use of oncoplastic reconstruction for breast-conserving surgery (BCS) extends benefits beyond merely minimizing poor cosmetic results. However, the feasibility and oncological safety of oncoplastic surgery (OPS) are controversial. METHODS: This meta-analysis aimed to compare the short-term and long-term oncological outcomes of BCS alone and BCS plus OPS. Relevant studies published before July 2017 in the Embase, the Cochrane Library, PubMed, and Web of Science databases were screened and collected. The meta-analysis was performed using STATA software (Stata Corp.). RESULTS: A total of 3,789 patients from 11 studies were included, with 2,691 patients in the BCS-alone group and 1,098 patients in the BCS plus OPS group. The demographics were similar between both groups, and no significant difference was observed in pathological T and N stages between the two groups. Re-excision was less common (relative risk [RR], 0.66; p=0.009) and the positive-margin rate was lower, but not significantly (RR, 0.83; p=0.191), in the BCS plus OPS group than in the BCS-alone group. The local and distal recurrence rates were similar in both groups. Both disease-free survival (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.96-1.49; p=0.112) and overall survival (HR, 1.14; 95% CI, 0.76-1.69; p=0.527) did not differ between the two groups. CONCLUSION: A combination of BCS and OPS is preferred over BCS alone for decreasing re-excisions and provides similar long-term survival as BCS alone in patients with breast cancer.
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Our previous studies have shown that recombinant human phospholipase D2 (rhPLD2) plays a modulator role on NF-κB and PKC signaling pathways. It also inhibits IL-5-induced inflammatory response in chronic asthmatic guinea pigs. Additionally, increasing evidence also has revealed that the adoptive transfer of induced regulatory T cells (Tregs) may be a therapeutic solution to airway allergic diseases. To investigate the epigenetic, transcriptomic and phenotypic variability of Treg population in an ovalbumin (OVA)-induced airway inflammation model derived from the induction of rhPLD2, OVA-induced asthmatic murine model is used in this study. The lung inflammation, eosinophil infiltration, the differentiation and proliferation of T helper cells and the amplification of Tregs were examined in this mouse model with and without rhPLD2 induction. Our data showed that rhPLD2 administration in asthmatic mice significantly increases CD4+CD25+ Foxp3+ Treg cell numbers and alleviates lung inflammation. The addition of rhPLD2 in vitro enhanced the demethylation of Treg-specificdemethylated region (TSDR) in iTregs, suggesting that rhPLD2 protein may be involved in improving the quality and quantity of Treg cells that eventually significantly reduces lung inflammation in asthmatic murine model. These results suggest that rhPLD2 could have a clinical impact treating patients with allergic airway inflammation via promoting and stabilizing iTreg differentiation and function.
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Asma/tratamento farmacológico , Asma/imunologia , Fatores de Transcrição Forkhead/metabolismo , Inflamação/tratamento farmacológico , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Pulmão/patologia , Fosfolipase D/uso terapêutico , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Animais , Asma/patologia , Ilhas de CpG/genética , Metilação de DNA/genética , Modelos Animais de Doenças , Eosinófilos/patologia , Humanos , Camundongos Endogâmicos BALB C , Modelos Biológicos , Fosfolipase D/farmacologia , Estabilidade Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder characterized by inflammation, representing a significant leading cause of chronic morbidity and mortality. Reports have implicated hydrogen sulfide (H2S) in both the pathology and treatment of COPD. The present study aimed to explore the effects involved with exogenous H2S on endoplasmic reticulum stress (ERS) and pulmonary artery endothelial cells (PAECs) in a rat model of COPD. METHODS: Rat models of COPD were successfully established by means of passive smoke exposure and intratracheal injection with lipopolysaccharide (LPS). Pulmonary function tests were performed and histopathological changes were observed. The expression of ERS markers, glucose-regulated protein-78 (GRP78), and C/EBP homologous protein (CHOP) and caspase-12, associated with ERS-induced apoptosis, were determined by western blot and immunohistochemistry methods. TUNEL assay was applied to determine the apoptosis index (AI) in PAECs. RESULTS: Treatment with NaHS was followed by the exhibition of markedly increased forced expiratory volume over 0.3â¯s (FEV0.3)/forced vital capacity (FVC) and dynamic lung compliance as well as integral optical density (IOD), with decreased RI among COPD rats. Western blot analysis, immunohistochemistry and TUNEL assay results revealed there to be reduced expressions of GRP78, CHOP and caspase-12 in the lung tissues and AI of PAECs, post NaHS treatment. CONCLUSION: The key findings of the current study highlight ERS in COPD rats, as well as well as reduced apoptosis in PAECs in connection with exogenous H2S by suppressing ERS.
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Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Artéria Pulmonar/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Sulfetos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Masculino , Substâncias Protetoras/administração & dosagem , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Ratos Sprague-Dawley , Testes de Função Respiratória , Sulfetos/administração & dosagemRESUMO
BACKGROUND: Uterine leiomyoma is one of the most common benign tumors in women. It dramatically decreases the quality of life in the affected women. However, there is a lack of effective treatment paradigms. Micro-RNAs are small noncoding RNA molecules that are extensively expressed in organisms, and they are interrelated with the occurrence and development of the tumor. miR-139-5p was found to be downregulated in various cancers, but its function and mechanism in uterine leiomyoma remain unknown. The aim of this study was to investigate the role of miR-139-5p and its target gene in uterine leiomyoma. METHODS: By using a bioinformatic assay, it was found that TPD52 was a potential target gene of miR-139-5p. Then, expressions of miR-139-5p and TPD52 in uterine leiomyoma and adjacent myometrium tissues were evaluated by quantitative real-time polymerase chain reaction and Western blot. Proliferation, apoptosis, and cell cycle of uterine leiomyoma cells transfected by miR-139-5p mimics or TPD52 siRNA were determined. RESULTS: It was observed that the expression of miR-139-5p in uterine leiomyoma tissues was significantly lower (P<0.001) than that in the adjacent myometrium tissues. Overexpression of miR-139-5p inhibited the growth of uterine leiomyoma cells and induced apoptosis and G1 phase arrest. Dual-luciferase reporter assay and Western blot validated that TPD52 is the target gene of miR-139-5p. Furthermore, downregulation of TPD52 by siRNA in uterine leiomyoma cells inhibited cell proliferation and induced cell apoptosis and G1 phase arrest. CONCLUSION: Data suggested that miR-139-5p inhibited the proliferation of uterine leiomyoma cells and induced cell apoptosis and G1 phase arrest by targeting TPD52.
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The modification of cardiovascular stent surface for a better micro-environment has gradually changed to multi-molecule, multi-functional designation. In this study, heparin (Hep) and type IV collagen (IVCol) were used as the functional molecule to construct a bifunctional micro-environment of anticoagulation and promoting endothelialization on titanium (Ti). The surface characterization results (AFM, Alcian Blue 8GX Staining and fluorescence staining of IVCol) indicated that the bio-layer of Hep and IVCol were successfully fabricated on the Ti surface through electrostatic self-assembly. The APTT and platelet adhesion test demonstrated that the bionic layer possessed better blood compatibility compared with Ti surface. The adhesion, proliferation, migration and apoptosis tests of endothelial cells proved that the Hep/IVCol layer was able to enhance the endothelialization of the Ti surface. The in vivo animal implantation results manifested that the bionic surface could encourage new endothelialization. This work provides an important reference for the construction of multifunction micro-environment on the cardiovascular scaffold surface.
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Colágeno Tipo IV/fisiologia , Heparina/química , Titânio/química , Animais , Materiais Biocompatíveis , Colágeno Tipo IV/química , Cães , Células Endoteliais/fisiologia , Artéria Femoral , Heparina/fisiologia , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Propriedades de SuperfícieRESUMO
AIM: To investigate the influence of nodal status on response and clarify the optimal treatment for operable esophageal squamous cell carcinoma (OSCC). METHODS: We retrospectively analyzed 1490 OSCC patients who underwent transthoracic esophagectomy and lymphadenectomy between December 1996 and December 2009 at the Sun Yat-sen University Cancer Center. The surgical approach and the number of resected lymph nodes (LNs) were considered in the assessment of surgery. Patients were classified according to their nodal statuses (N0 vs N1 vs N2-3). Overall survival was defined as the time from the date of death or final follow-up. Survival analysis was performed using the Kaplan-Meier method and differences between curves were assessed by the log-rank test. Univariate and multivariate Cox regression analyses were used to identify factors associated with prognosis. Statistical significance was assumed at a P < 0.05. RESULTS: With a median time from surgery to the last censoring date for the entire cohort of 72.2 mo, a total of 631 patients were still alive at the last follow-up and the median survival time was 35.5 mo. The surgical approach (left transthoracic vs Ivor-Lewis/tri-incisional) was verified as independent prognostic significance in patients with N0 or N1 status, but not in those with N2-3 status. Similar results were also observed with the number of resected LNs (≤ 14 vs ≥ 15). Compared with surgery alone, combined therapy achieved better outcomes in patients with N1 or N2-3 status, but not in those with N0 status. For those with N2-3 status, neither the surgical approach nor the number of resected LNs reached significance by univariate analysis, with unadjusted HRs of 0.826 (95%CI: 0.644-1.058) and 0.849 (95%CI: 0.668-1.078), respectively, and aggressiveness of surgery did not influence the outcome; the longest survival was observed in those patients who received the combined therapy. CONCLUSION: Combined therapy has a positive role in OSCC with LN metastasis, and aggressive surgical resection does not improve survival in patients with N2-3 status.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Excisão de Linfonodo/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , China , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia/efeitos adversos , Esofagectomia/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The transcription factor forkhead box F2 (FOXF2) is an evolutionarily conserved DNA-binding protein involved in embryogenesis and metabolism. Although recent studies prove that FOXF2 is a tumor suppressor in various human cancers, the role of FOXF2 in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, samples were collected from 188 ESCC patients, including 33 pairs of tumor and non-tumor tissues, and FOXF2 mRNA expression was investigated by quantitative polymerase chain reaction. The results demonstrated that FOXF2 mRNA is downregulated in tumor tissues compared to paired non-tumor tissues (P=0.048). The receiver operating characteristic curve analysis indicated 1.2 as a cut-off point and, thus, 125 and 63 tumors were classified as low- and high-level FOXF2 mRNA expression, respectively. We observed that low-level FOXF2 mRNA expression in the tumors was associated with a higher frequency of lymph node metastasis (P=0.044), an effect further suggested by the multivariate logistic regression analysis (P=0.060). According to the univariate Cox analysis, patients harboring tumors with low-level FOXF2 mRNA expression had a significantly increased mortality risk compared to those with high-level expression (hazard ratio=1.700, 95% confidence interval, 1.077-2.681), with 5-year survival rates of 41.1 and 61.9%, respectively. This negative prognostic effect of low-level FOXF2 mRNA expression was further validated in the multivariate Cox analysis (P=0.021). The subgroup analysis demonstrated that the effect of FOX2 mRNA expression was limited to male patients and those with advanced-stage disease. Taken together, these findings suggest that FOXF2 may be an anti-oncogene for ESCC and decreased FOXF2 mRNA expression is associated with a poor prognosis in patients with ESCC.
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Driven by the complications occurring with bare metal stents and drug-eluting stents, concerns have been raised over strategies for long-term safety, with respect to preventing or inhibiting stent thrombosis, restenosis, and in-stent restenosis in particularly. Surface modification is very important in constructing a buffer layer at the interface of the organic and inorganic materials and in ultimately obtaining long-term biocompatibility. In this review, we summarize the developments in surface modification of implanted cardiovascular metal stents. This review focuses on the modification of metal stents via coating drugs or biomolecules to enhance antithrombosis, antirestenosis, and/or endothelialization. In addition, we indicate the probable future work involving the modification of the metallic blood-contacting surfaces of stents and other cardiovascular devices that are under development.
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Materiais Revestidos Biocompatíveis/química , Stents Farmacológicos , Oclusão de Enxerto Vascular/prevenção & controle , Trombose/prevenção & controle , Animais , Oclusão de Enxerto Vascular/metabolismo , Humanos , Trombose/metabolismoRESUMO
To select the adaptive strain of Dengue-III virus D9964 strain (China strain) in KMB17 cells, elucidate the biological characteristics and proliferation kinetics of adapted strain,and to lay the foundation for the development dengue inactivated vaccine and attenuated live vaccine. Dengue-III virus D9964 strain was firstly identified by amplification of the type-specific gene segment of dengue virus by RT-PCR, and the titer was determined. The virus was then subcultured in KMB17 cells with 4.0 MOI till completely adaptive to multiply in cell S. After subculturing in KMB17 cells for 10 consecutive passages, the adapted strain was screened, and purified through plaque. Virus titer of each passage was measured by microtitrimetry, and the antigenicity was detected by IFA. The purified virus RNA extraction of 3-8 day cultured from KMB17 cells, was performed to detect the proliferation kinetics of adapted strain. The results showed that after continuous subculture, dengue-III virus D9964 (China) strain could stably proliferate in KMB17 cells, a highly puried virus adapted strain was obtained through plaque purification. Purified strain maintained the good antigenicity with a highest replicating activity during the 5th-6th day.
Assuntos
Vírus da Dengue/crescimento & desenvolvimento , Dengue/virologia , Replicação Viral , Linhagem Celular , Vírus da Dengue/química , Vírus da Dengue/genética , Vírus da Dengue/fisiologia , Humanos , Cinética , Cultura de VírusRESUMO
To analyze the genomic sequence characteristics of a human Echovirus 9(ECHO-9) strain isolated from a child with Hand-foot-mouth disease (HFMD) in Kunming, Yunnan Province, in 2010. The complete genome sequence of a human echovirus 9 strain, MSH-KM812-2010 was determined. As other human enterovirus, its genome was 7,424 nucleotides (nts) in length and encoded for 2,203 amino acids (aas). In comparison to other human enteroviruses, MSH-KM812-2010 strain had the highest homology with other strains of human echovirus 9 in structural genomic regions and more homologous to other serotypes of B specie than to human echovirus 9 in non-structural genomic regions. Phylogenetic analysis based on complete VP1 gene revealed that the sequences of human echovirus 9 segregated into three distinct clades A, B and C with more than 15. 0% diversity between clades. All Chinese isolates belonged to the same clade. RDP3 and Blast revealed evident recombination in non-structural genomic regions. This report is the first to, describe the complete genome of the human echovirus 9 in China and provide an overview of the diversity of genetic characteristics of a circulating human echovirus 9.