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Background: This study aimed to investigate the effects of adjuvant beam radiation therapy (ABRT) on overall survival (OS) in patients with primary single intracranial atypical meningioma (AM), with a focus on age-related outcomes. Methods: We conducted a retrospective study using data from SEER database. Our cohort consisted of patients diagnosed with a primary single intracranial AM tumor and had undergone surgery. The primary endpoint was OS. For survival analysis, univariable and multivariable Cox regression analysis were performed. A multivariable additive Cox model was used to assess the functional relationship between age and OS in patients with or without ABRT. Results: Of the 2,759 patients included, 1,650 underwent gross total resection and 833 received ABRT. Multivariable Cox analysis indicated that ABRT did not significantly influence OS across the entire cohort. According to the multivariable generalized additive Cox model, the relative risk of all-cause mortality increased with advancing age in both ABRT-yes and ABRT-no group. ABRT-yes had a lower relative risk than ABRT-no when age ≤ 55 years old while a higher relative risk when age > 55 years old. Subsequent multivariable Cox analysis showed that ABRT was associated with a significant lower risk for all-cause mortality in patients with age ≤ 55 years old while a significant higher risk in patients with age > 55 years old. Conclusion: Our study found that ABRT enhanced OS in younger primary single intracranial AM patients. But we also revealed a negative correlation between OS and ABRT in older patients.
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Ultrathin MXene composite films, with their flexibility, metal-level conductivity, and multifunction compatibility, are an ideal choice for electromagnetic interference (EMI) shielding materials in future developments. Nonetheless, the dilemma between electrical conductivity and robustness in these composite films remains a challenge. Herein, an ammonium polyphosphate (APP) assisted interfacial multiple cross-linking strategy, achieved via simple solution blending and filtration, was employed to reinforce and toughen the "brick-mortar" layered MXene/bacterial cellulose (MBCA) films without compromising their conductivity and EMI shielding ability. The introduction of a small amount of APP leads to multiple interfacial interactions between MXene and bacterial cellulose, resulting in significant enhancements in mechanical strength (360.8 MPa), Young's modulus (2.8 GPa), fracture strain (17.3%), and toughness (34.1 MJ/m3). Concurrently, the MBCA film displayed satisfactory conductivity values of 306.7 S/cm and an EMI SE value of 41 dB upon optimizing the MXene content. Additionally, the MBCA film demonstrated a consistent, rapid-response photothermal conversion capability, achieving a photothermal conversion temperature of 97 °C under a light intensity of 200 mW/m2. Consequently, this tough and multifunctional EMI shielding film holds substantial promise for protecting electronic equipment.
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Objectives: To understand the different characteristics and growth corridors of knosp grade 4 pituitary adenomas (Knosp4PA) with cavernous sinus (CS) compartments penetration and intracranial extension, aiming to improve the safety, effectiveness, and total resection rate of surgery. Methods: A case series of 120 Knosp4PA patients with 187 invaded compartments were retrospectively reviewed. A novel surgery-relevant grading system was proposed according to the CS penetrating features. The details of approach drafting, risk prediction, and complication avoidance were analyzed and integrated through illustrated cases. Results: All enrolled tumor was Knosp4PA which was derived from Knosp subgrades 3A(62.5%) and 3B(37.5%). Based on the tumor growth pathway and its relevant features, five subclassifications of intracranial extension(n=98,81.7%) were classified, which derived from the superior (Dolenc's and Oculomotor subtype, 5% and 24.2%), lateral (Parkinson's subtype,18.3%), and posterior (cerebral peduncle and Dorello's subtype, 5.8% and 1.7%) CS compartment penetration. The size of intracranial extension is assessed by Lou's scale proposed here based on preoperative MRI characteristics. Under Lou's scale, the gross total rate (GTR) decreased (82%, 53%, 22%, and 19%) with grades increased (grade 0,1,2,3, respectively), and presents significant difference between the four groups (p=0.000), as well as between single and multiple compartments involved (p=0.001). Preoperative cranial nerve deficits included the optic nerve (53%), oculomotor nerve (24.2%), and abducent nerve (4.2%), with an overall rate of visual function improvement in 68.1%. Postoperative complications of transient diabetes insipidus, cerebrospinal fluid (CSF) leakage, and cranial nerve deficits were 6.7%, 0.8%, and 0%. No new cranial nerve deficits occurred. The mortality rate was 0.8%. Conclusion: The concept of "penetration" refines the extracavernous growth pattern, and the five intracranial subclassifications help to understand the potential extension corridors, enhancing adequate exposure and targeted resection of Knosp4PA. This grading system may benefit from its predictive and prognostic value, from which a higher GTR rate can be achieved.
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OBJECTIVE: To examine the prognostic value of HRV measurements during anesthesia for postoperative clinical outcomes prediction using machine learning models. DATA SOURCES: VitalDB, a comprehensive database of 6388 surgical patients admitted to Seoul National University Hospital. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Cases with ECG lead II recording duration of less than one hour were excluded. Cases with more than 20% of missing HRV measurements were also excluded. A total of 5641 cases were eligible for the analyses. METHODS: Six machine learning models including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Trees (GBT), Extreme Gradient Boosting (XGB), and an ensemble of the five baseline models were developed to predict postoperative clinical outcomes. The prediction models were trained using only clinical information, and using both clinical information and HRV features, respectively. Feature importance based on the SHAP method was used to assess the contribution of the HRV measurements to the outcome predictions. Subgroup analysis was also performed to evaluate the risk association between postoperative ICU stay and various HRV measurements such as heart rate, low-frequency power (LFP), and short-term fluctuation DFA [Formula: see text]. RESULT: The final cohort included 5641 unique cases, among whom 4678 (83.0%) cases had ages over 40, 2877 (51.0%) were male, 1073 (19.0%) stayed in ICU after surgery, 52 (0.9%) suffered in-hospital death, and 3167(56.1%) had a total length of hospital stay longer than 7 days. In the final test set, the highest AUROC performance with only clinical information was 0.79 for postoperative ICU stay, 0.58 for in-hospital mortality, and 0.76 for the total length of hospital stay prediction. Importantly, using both clinical information and HRV features, the AUROC performance was 0.83, 0.70, and 0.76 for the three clinical outcome predictions, respectively. Subgroup analysis found that patients with an average heart rate higher than 70, low-frequency power (LFP) < 33, and short-term fluctuation DFA [Formula: see text] < 0.95 during anesthesia, had a significantly higher risk of entering the ICU after surgery. CONCLUSION: This study suggested that HRV measurements during anesthesia are feasible and effective for predicting postoperative clinical outcomes.
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Anestesia , Anestesiologia , Humanos , Frequência Cardíaca , Mortalidade Hospitalar , PrognósticoRESUMO
BACKGROUND: The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined. METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan-Meier curves, and subgroup analyses were conducted. RESULTS: The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk of major adverse cardiac events (MACE) (0.51% vs. 1.43%, P = 0.007), and all-cause death (0.36% vs. 0.99%, P = 0.028), the risks of myocardial infarction and major bleeding were not significantly different between patients with and without reloading. In survival analysis, a lower cumulative risk of MACE could be identified (Log-rank test, P = 0.007) in reloading group. In the unadjusted Cox model, reloading P2Y12 receptor inhibitors was associated with a decreased risk of MACE [HR, 0.35; 95% CI 0.16-0.78; (P = 0.010)] and all-cause death [HR, 0.37; 95% CI 0.14-0.94; (P = 0.036)]. Reloading of P2Y12 receptor inhibitors was associated with a decreased risk of MACE in most of the subgroups. CONCLUSIONS: In NSTEACS patients already taking P2Y12 receptor inhibitors, we observed a decreased risk of in-hospital MACEs and all-cause mortality and did not observe an increased risk of major bleeding, with reloading. The differential profile in the two groups might influence this association and further studies are warranted. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov (Unique identifier: NCT02306616, date of first registration: 03/12/2014).
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Síndrome Coronariana Aguda , Doenças Cardiovasculares , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Doenças Cardiovasculares/etiologia , Síndrome Coronariana Aguda/tratamento farmacológico , Melhoria de Qualidade , Fatores de Risco , Resultado do Tratamento , Hemorragia/etiologia , Hospitais , Intervenção Coronária Percutânea/efeitos adversosRESUMO
Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is characterized by rapid development of neuron apoptosis and dysregulated inflammatory response. Microglia efferocytosis plays a critical role in the clearance of apoptotic cells, attenuation of inflammation, and minimizing brain injury in various pathological conditions. Here, using a mouse SAH model, we aim to investigate whether microglia efferocytosis is involved in post-SAH inflammation and to determine the underlying signaling pathway. We hypothesized that TAM receptors and their ligands regulate this process. To prove our hypothesis, the expression and cellular location of TAM (Tyro3, Axl, and Mertk) receptors and their ligands growth arrest-specific 6 (Gas6) and Protein S (ProS1) were examined by PCR, western blots, and fluorescence immunostaining. Thirty minutes after SAH, mice received an intraventricular injection of recombinant Gas6 (rGas6) or recombinant ProS1 (rPros1) and underwent evaluations of inflammatory mediator expression, neurological deficits, and blood-brain barrier integrity at 24 h. Microglia efferocytosis of apoptotic neurons was analyzed in vivo and in vitro. The potential mechanism was determined by inhibiting or knocking down TAM receptors and Rac1 by specific inhibitors or siRNA. SAH induced upregulation of Axl and its ligand Gas6. The administration of rGas6 but not rPros1 promoted microglia efferocytosis, alleviated inflammation, and ameliorated SAH-induced BBB breakdown and neurological deficits. The beneficial effects of rGas6 were arrogated by inhibiting or knocking down Axl and Rac1. We concluded that rGas6 attenuated the development of early brain injury in mice after SAH by facilitating microglia efferocytosis and preventing inflammatory response, which is partly dependent on activation of Axl and Rac1.
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Lesões Encefálicas , Hemorragia Subaracnóidea , Animais , Microglia/patologia , Hemorragia Subaracnóidea/patologia , Transdução de Sinais , Inflamação/metabolismo , Modelos Animais de DoençasRESUMO
It is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.
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Proteínas de Ciclo Celular/biossíntese , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , Animais , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Masculino , RNA Longo não Codificante/antagonistas & inibidores , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The inflammatory status of epicardial adipose tissue (EAT) is one of the factors leading to the development of related diseases such as coronary artery disease (CAD). The thickness of CAD EAT increases and is accompanied with increased macrophage infiltration and heightened inflammatory responses. However, microRNAs (miRNAs) regulating the inflammatory responses of macrophages in CAD EAT remain unclear. METHOD: miRNA expression profiles of CAD EATs and non-CAD EATs were determined by miRNA microarrays. Quantitative real-time reverse transcription-polymerase chain reaction, Western blotting, immunohistochemical assay, and fluorescence in-situ hybridization were adopted to detect miR-3614 expression and function in EATs and macrophages. The interaction between miR-3614 and tumor necrosis factor receptor-associated factor 6 (TRAF6) was identified using an online website combined with a dual-luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the expression of inflammatory cytokines. RESULTS: The decreased expression of miR-3614 was identified in CAD EAT. The level of miR-3614 was down-regulated by lipopolysaccharide (LPS) in macrophages, whereas LPS-induced inflammatory injury can be reduced by miR-3614 overexpression. TRAF6 was predicted and verified to be a target of miR-3614. The phosphorylated levels of kinases in the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways were inhibited by miR-3614 overexpression. Importantly, the knockdown of TRAF6 inhibited the LPS-induced inflammatory cytokine expressions in cells. CONCLUSION: A novel negative feedback loop by miR-3614 possibly contribute to the regulation of inflammatory processes via targeting the TRAF6/MAPK/NF-κB pathway in EATs and prevents an overwhelming inflammatory response.
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Tecido Adiposo , Doença da Artéria Coronariana , MicroRNAs , Fator 6 Associado a Receptor de TNF , Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/genética , Humanos , Inflamação/genética , Peptídeos e Proteínas de Sinalização Intracelular , Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , NF-kappa B/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismoRESUMO
As the impairment of myocardial microenvironments due to coronary microembolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME. Low- (2 × 105) and high- (2 × 106) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood-clots into the left ventricle. Echocardiograph was examined before and 1, 7, and 28 days after EPC transplantation; serum cardiac troponin I (cTNI), von Willebrand factor (vWF), and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and vascular endothelial growth factor (VEGF), vWF, and basic fibroblast growth factor (bFGF) expression were examined one day after EPC transplantation. After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by left ventricular ejection fraction significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a proangiogenic, antifibroblast, antifibrosis, and antinecrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.
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Doença da Artéria Coronariana/terapia , Vasos Coronários/metabolismo , Embolia/terapia , Células Progenitoras Endoteliais/citologia , Infarto do Miocárdio/terapia , Miocárdio/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Ratos Wistar , Transplante de Células-Tronco/métodos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
OBJECTIVE: Recently, the function of microRNAs (miRNAs) has been clarified in human diseases, we aimed to identify the role of miR-185 in myocardial infarction (MI). METHODS: Bone marrow mesenchymal stem cells (BMSCs) were cultured, from which the exosomes were extracted. MI mice models were established by coronary artery ligation and injected with transfected BMSCs. The echocardiographic and ventricle indicators, and hemodynamics of mice were measured. Moreover, the ultrastructure and apoptosis of cardiomyocytes were determined, and expression of miR-185, suppressor of cytokine signaling 2 (SOCS2), collagens, and apoptotic proteins in myocardial tissues were evaluated. RESULTS: MiR-185 was poorly expressed in myocardial tissues of MI mice. BMSCs-Exo could shuttle miR-185 to promote cardiac function and attenuate myocardial injury of myocardial tissues in MI mice, and also could protect cardiomyocytes from apoptosis in MI mice by reducing the expression of SOCS2. SOCS2 was determined to be the direct target gene of miR-185. Overexpressed SOCS2 could block the cardioprotective effect of BMSCs-derived exosomal miR-185 in MI mice. CONCLUSION: We have found in this study that BMSCs-derived exosomal miR-185 could repress ventricular remolding of MI mice by inhibiting SOCS2. This study may provide new method for MI treatment.
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Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Remodelação Ventricular/genética , Animais , Apoptose/genética , Apoptose/imunologia , Linhagem Celular , Modelos Animais de Doenças , Ecocardiografia , Exossomos/metabolismo , Exossomos/transplante , Ventrículos do Coração/citologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/imunologia , Ventrículos do Coração/patologia , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Camundongos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/terapia , Miócitos Cardíacos , Remodelação Ventricular/imunologiaRESUMO
BACKGROUND: Low concentration C-reactive protein (CRP) has favorable prognostic significance in patients with cardiovascular risks. METHODS: We compared the wr-CRP method with the hs-CRP method both on Roche Cobas c702 analyzer for the determination of low CRP concentration (<20 mg/L) including 200 patients treated in Cardiology Department in Beijing Tsinghua Changgung Hospital (Beijing, China) from December 2018 to March 2019. RESULTS: The two methods were highly correlated (Spearman's rho = 0.995). Deming regression was used to fit the regression analysis model, giving a slope of 1.058 with an intercept of 0.008. The median method difference (wr-CRP - hr-CRP) was 0.120 mg/L (95% CI, 0.086-0.200 mg/L), and the median percent differences were 7.34% (95% CI, 4.27%-8.47%). The percent bias between both methods at the given cutoff CRP values of 1, 3, and 10 mg/L evaluated by Deming regression was 6.60%, 6.07%, and 5.88%, respectively, all of which were less than the acceptable standard (12.50%). The percentage of sample results concordant by both methods for the risk stratification was 96.0% (kappa = 0.937, P < 0.001). CONCLUSIONS: Roche wr-CRP and hs-CRP assays are highly concordant in determining low concentration CRP. Wr-CRP may be used as an alternative to hs-CRP assay on Roche Cobas c702 analyzer to assess the cardiovascular risk, considering its convenience and lower costs.
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Biomarcadores/sangue , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Testes Diagnósticos de Rotina/métodos , Programas de Rastreamento/métodos , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Testes Diagnósticos de Rotina/classificação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de RiscoRESUMO
The cytotropic heterogeneous molecular lipid (CHML) is a mixture of lipids isolated from natural products. CHML is an effective therapy for various kinds of cancers; however, the effect of CHML on glioma cells was seldom reported. Here, we aim to explore the cytotoxicity of CHML on glioma cells, and analyze the possible mechanisms. U251 glioma cells were cultured with CHML at different concentration, and the growth inhibition was measured by CCK-8 assay. Induced apoptosis were detected by flow cytometry, and the induced autophagies were observed by a transmission electron microscope. The key molecules involved in apoptosis and autophagy were detected by quantitative PCR and western-blot. CHML might inhibit the growth of U251 cells and promote apoptosis by up-regulating the expressions of Caspase-8 and Caspase-3; CHML also induced autophagy of U251 cells by promoting the expressions of MAP LC-3 and Beclin-1. CHML can inhibit proliferation of U251 cells by promoting cell apoptosis and inducing autophagy.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ácidos Graxos Insaturados/farmacocinética , Glioma/tratamento farmacológico , Western Blotting , Caspase 3/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Microscopia Eletrônica de Transmissão , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND AND STUDY AIMS: Computed tomography (CT) and magnetic resonance image (MRI) data have been widely used to for navigation in various neurosurgical operations. However, delicate intracranial structures cannot be displayed using only one imaging method. Navigation with multimodality imaging was developed to better visualize these structures in glioma removal, but whether it is useful in endoscopic transsphenoidal surgery is unknown. We describe our clinical experience using multimodality imaging for navigation in endoscopic transsphenoidal surgeries. MATERIAL AND METHODS: A total of 134 patients underwent endoscopic transsphenoidal surgery with navigation using multimodality imaging. CT and MR images were fused and processed to optimally visualize anatomical structures of the sphenoidal sinus and tumor. RESULTS: Navigation with multimodality imaging offers a precise display of anatomical structures in the sphenoid sinus as compared with navigation based on either CT or MRI. CONCLUSION: Navigation with multimodality imaging is capable of providing optimized guidance during endoscopic transsphenoidal surgeries. The fused images allow precise visualization of sphenoidal sinus structures, lesions and tumors. This is valuable for increasing safety in cases of anatomical variations and potentially decreasing the rate of tumor recurrence.
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Neoplasias Encefálicas/cirurgia , Endoscopia/métodos , Imagem Multimodal/métodos , Procedimentos Neurocirúrgicos/métodos , Seio Esfenoidal/cirurgia , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Glioma/diagnóstico por imagem , Glioma/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Seio Esfenoidal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
Temozolomide (TMZ) is commonly used in glioblastoma (GBM) chemotherapy. However, a great challenge for TMZ treatment is the rapid development of resistance and subsequent tumor recurrence and poor outcome. In the present study we established TMZ-resistant GBM cells (U87-TR and U251-TR) and found that the expression of PomGnT1 was significantly upregulated in TMZ-resistant GBM cells compared with the TMZ-sensitive counterparts. Furthermore, overexpression of PomGnT1 in U87-MG and U251-MG cells led to increased IC50 values for TMZ and reduced apoptosis of cells. Knockdown of PomGnT1 in both U87-TR and U251-TR cells led to decreased IC50 values for TMZ and enhanced apoptosis. Biochemical analysis revealed that PomGnT1 regulates the expression of factors in epithelial-mesenchymal transition signaling including TCF8, vimentin, ß-catenin and Slug in GBM cells. These findings demonstrate that PomGnT1 might be a new focus of GBM research for treatment of recurrent TMZ-resistant GBM.
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Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , N-Acetilglucosaminiltransferases/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dacarbazina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Lentivirus/genética , Camundongos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Transdução de Sinais/efeitos dos fármacos , Temozolomida , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genéticaRESUMO
Glioma is the most common and malignant brain tumor with extremely poor prognosis. It is crucial to understand the molecular characteristics of glioma and find out more effective therapeutic targets for the treatment of glioma. USP17 is a novel deubiquitinating enzyme that is differentially expressed in certain types of solid tumor. Our present study investigated the pathological functions and clinical significance of USP17 in glioma for the first time. We found that USP17 was down-regulated in glioma tissue compared with normal tissues. Overexpression of USP17 in glioma cells reduced their tumorigenesis and proliferation ability through reducing Ras and Myc protein levels. Subsequent in vivo experiments showed that overexpression of USP17 suppressed tumor progression in an orthotopic glioma models. Further, study of a cohort of 104 patients with stage I-IV glioma showed that USP17 expression was negatively associated with the WHO grade (p<0.001). USP17 was more highly expressed in low grade (I+II) glioma than high-grade (III+IV) glioma (p<0.001). Taken together, our results indicate that USP17 might play important functions in glioma through suppressing glioma tumorigenesis and proliferation.
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Neoplasias Encefálicas/enzimologia , Endopeptidases/metabolismo , Glioma/enzimologia , Animais , Neoplasias Encefálicas/patologia , Proliferação de Células , Regulação para Baixo , Endopeptidases/genética , Feminino , Glioma/patologia , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Transplante de NeoplasiasRESUMO
OBJECTIVE: To analyze the safety and efficacy of surgical removal of recurrent or regrowing pituitary adenomas by endoscopic endonasal transsphenoidal approach. METHODS: The clinical data were retrospectively reviewed for 28 patients undergoing endoscopic endonasal transsphenoidal surgery for recurrent or regrowing pituitary adenomas between April 2010 and December 2013. There were 9 males and 19 females with a mean age of 44. 2 (11 - 73) years. The maximal tumor diameter ranged from 2. 1 to 6.9 cm. The Knosp grades were 1 -2 (n = 11), 3 (n =8) and 4 (n =9). Fifteen tumors were endocrinically functional and the remainder endocrinically nonfunctional. All operations were performed with an assistance of intraoperative neuronavigation. Neuro-ophthalmological, neuroimaging and endocrinological results were followed up postoperatively. And surgical outcomes and risk factors were analyzed for incomplete tumor resection in previous operations. RESULTS: The mean follow-up period was 19. 1 (3 - 45) months. Gross total resection(n = 18, 64. 3%), subtotal resection(n = 6, 21. 4%) and partial resection(n = 4, 14. 3%) were achieved. Postoperatively, visual acuity improved in 11 patients (73. 3%) and 6 patients (40. 0%) showed endocrine remission. Qne patient had short-term postoperative leakage of cerebrospinal fluid (CSF). CONCLUSION: Endoscopic endonasal transsphenoidal surgery is both safe and effective for recurrent or regrowing pituitary adenomas.
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Adenoma , Neoplasias Hipofisárias , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Laringoscopia , Masculino , Pessoa de Meia-Idade , Neuroimagem , Neuronavegação , Nariz , Complicações Pós-Operatórias , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Glioma is the most common form of primary brain tumor. Increasing evidence show that IDH1 gene mutation is implicated in glioma. However, the mechanism involved in the progression of glioma remains unclear until now. In the study reported here, we used gene chip to identifying the genes regulated with IDH mutanted at R132. The results showed that IDH1-mutant leads to 1255 up-regulated genes and 1862 down-regulated genes in U87 cell lines. Meanwhile, GO and gene-network was performed and shown IDH1-mutant mainly affect small molecule metabolic process, mitotic cell cycle and apoptosis. This result will lay a foundation for further study of IDH1 gene function in the future.
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Previous studies evaluating the association between the XPG Asp1104His polymorphism and melanoma susceptibility remained controversial. To draw a more precise estimation of the relationship, a total of eight published case-control studies containing 5,212 cases and 7,045 controls were included for meta-analysis. Overall, a significant association was found between the XPG Asp1104His polymorphism and melanoma susceptibility for the dominant model (OR = 2.42, 95 % CI = 2.26-2.60). In subgroup analysis by source of control, there was an obvious association was found among Population-based subgroup for the dominant model CC+GC vs GG (OR 2.51, 95 % CI 2.28-2.77), among the Hospital-based subgroup, an obvious association was also found for the dominant model CC+GC vs GG (OR 2.34, 95 % CI 2.12-2.58). This meta-analysis suggested that the XPG Asp1104His polymorphism was a risk factor for melanoma susceptibility.