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1.
J Am Chem Soc ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39049158

RESUMO

The formation and preservation of the active phase of the catalysts at the triple-phase interface during CO2 capture and reduction is essential for improving the conversion efficiency of CO2 electroreduction toward value-added chemicals and fuels under operational conditions. Designing such ideal catalysts that can mitigate parasitic hydrogen generation and prevent active phase degradation during the CO2 reduction reaction (CO2RR), however, remains a significant challenge. Herein, we developed an interfacial engineering strategy to build a new SnOx catalyst by invoking multiscale approaches. This catalyst features a hierarchically nanoporous structure coated with an organic F-monolayer that modifies the triple-phase interface in aqueous electrolytes, substantially reducing competing hydrogen generation (less than 5%) and enhancing CO2RR selectivity (∼90%). This rationally designed triple-phase interface overcomes the issue of limited CO2 solubility in aqueous electrolytes via proactive CO2 capture and reduction. Concurrently, we utilized pulsed square-wave potentials to dynamically recover the active phase for the CO2RR to regulate the production of C1 products such as formate and carbon monoxide (CO). This protocol ensures profoundly enhanced CO2RR selectivity (∼90%) compared with constant potential (∼70%) applied at -0.8 V (V vs RHE). We further achieved a mechanistic understanding of the CO2 capture and reduction processes under pulsed square-wave potentials via in situ Raman spectroscopy, thereby observing the potential-dependent intensity of Raman vibrational modes of the active phase and CO2RR intermediates. This work will inspire material design strategies by leveraging triple-phase interface engineering for emerging electrochemical processes, as technology moves toward electrification and decarbonization.

2.
Cell Mol Neurobiol ; 44(1): 14, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38158515

RESUMO

The existence of lymphatic vessels or similar clearance systems in the central nervous system (CNS) that transport nutrients and remove cellular waste is a neuroscientific question of great significance. As the brain is the most metabolically active organ in the body, there is likely to be a potential correlation between its clearance system and the pathological state of the CNS. Until recently the successive discoveries of the glymphatic system and the meningeal lymphatics solved this puzzle. This article reviews the basic anatomy and physiology of the glymphatic system. Imaging techniques to visualize the function of the glymphatic system mainly including post-contrast imaging techniques, indirect lymphatic assessment by detecting increased perivascular space, and diffusion tensor image analysis along the perivascular space (DTI-ALPS) are discussed. The pathological link between glymphatic system dysfunction and neurological disorders is the key point, focusing on the enlarged perivascular space (EPVS) and the index of diffusivity along the perivascular space (ALPS index), which may represent the activity of the glymphatic system as possible clinical neuroimaging biomarkers of neurological disorders. The pathological link between glymphatic system dysfunction and neurological disorders is the key point, focusing on the enlarged perivascular space (EPVS) and the index for of diffusivity along the perivascular space (ALPS index), which may represent the activity of the glymphatic system as possible clinical neuroimaging biomarkers of neurological disorders.


Assuntos
Sistema Glinfático , Doenças do Sistema Nervoso , Humanos , Sistema Glinfático/diagnóstico por imagem , Doenças do Sistema Nervoso/diagnóstico por imagem , Neuroimagem , Sistema Nervoso Central , Biomarcadores
3.
Oral Dis ; 29(8): 3298-3305, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35821655

RESUMO

OBJECTIVES: The therapeutic regimen of submandibular gland carcinoma (SGC) has not reached consensus, especially for the neck treatment of patients with cN0. MATERIALS AND METHODS: Patients with SGC were identified from the medical database of Shanghai Ninth People's Hospital. Kaplan-Meier analysis, univariate and multivariate Cox regression were employed to evaluate the survival and independent prognostic factors. RESULTS: Two hundred and fifteen patients with SGC were retrospectively reviewed. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 71.5% and 77.8%, respectively. Multivariate analysis revealed that histological grade, cT classification, cN classification, and perineural invasion (PNI) were independent prognostic factors for DFS, while histological grade, cT classification, cN classification, and age were those for OS. The neck dissection showed no significant survival benefit for patients with cN0. Lung was the most common site of distant metastasis (16.7%). CONCLUSIONS: Histological grade, cT classification, cN classification, age, and PNI were independent prognostic factors of patient with SGC, which should be the main considerations for making therapeutic regimens. Our study also verifies the neck dissection of patient with cN0 is unnecessary, and postoperative radiotherapy (PORT) is vital for patients with pN+.


Assuntos
Carcinoma de Células Escamosas , Neoplasias das Glândulas Salivares , Humanos , Prognóstico , Carcinoma de Células Escamosas/patologia , Estudos Retrospectivos , Glândula Submandibular/patologia , China , Neoplasias das Glândulas Salivares/patologia , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia
4.
Oral Dis ; 29(4): 1602-1612, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35199423

RESUMO

OBJECTIVES: To evaluate the prognostic and locoregional metastatic features of carcinoma ex pleomorphic adenoma of submandibular gland (SMG-CXPA) and improve the understanding of this uncommon condition. PATIENTS AND METHODS: We retrospectively reviewed patients who were diagnosed with SMG-CXPA. The survival data of SMG-CXPA patients were statistically analyzed using Cox regression and Kaplan-Meier method. The associations between cervical metastasis and clinicopathological parameters were evaluated using chi-squared test. Additionally, two different histological categories (histological grade and invasiveness) and their combination were evaluated with the Kaplan-Meier method and receiver operating characteristic curves. RESULTS: In total, 86 patients were diagnosed: 38 clinically node-negative, 31 pathologically node-negative, and 17 node-positive patients. Clinical tumor stage and histological grade were two independent prognostic factors for SMG-CXPA. There were significant correlations between sex, tumor size, clinical tumor stage, clinical lymph node stage, histological grade, invasiveness, malignant components, perineural invasion, and no specific criteria exist for the clinical outcome. CONCLUSION: SMG-CXPA is a high-grade malignancy with an unfavorable prognosis. Elective neck dissection should be performed in SMG-CXPA patients with a risk of locoregional metastasis. Histological grade seems to be a more valuable predictor of lymph node involvement than invasiveness.


Assuntos
Adenoma Pleomorfo , Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Adenoma Pleomorfo/cirurgia , Adenoma Pleomorfo/patologia , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias das Glândulas Salivares/patologia , Glândula Submandibular/patologia , Carcinoma/patologia
5.
Oral Dis ; 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36794916

RESUMO

OBJECTIVES: To analyze and summarize the clinicopathological features, risk factors for cervical nodal metastasis, and prognostic factors of malignant sublingual gland tumors (MSLGT). METHODS: Patients diagnosed with MSLGT were retrospectively reviewed from January 2005 to December 2017 at Shanghai Ninth Hospital. The clinicopathological features were summarized, and the correlations between clinicopathological parameters, cervical nodal metastasis, and local-regional recurrence were evaluated using the Chi-square test. Kaplan-Meier method and Cox regression analysis were performed to assess the survival and independent prognostic factors. RESULTS: Seventy-nine patients were included, and the 5-year overall survival and disease-free survival rates was 85.7% and 71.7%, respectively. Gender and clinical tumor stage were risk factors for cervical nodal metastasis. Tumor size and pathological lymph node (LN) stage were independent prognostic factors for adenoid cystic carcinoma (ACC) of the sublingual gland; while age, pathological LN stage, and distant metastasis were prognostic factors for patients with non-ACC of the sublingual gland. Patients with higher clinical stage were more likely to undergo tumor recurrence. CONCLUSIONS: Malignant sublingual gland tumors are rare, and neck dissection should be performed in male MSLGT patients with higher clinical stage. Among patients with both ACC and non-ACC MSLGT patients, pN+ indicate a poor prognosis.

6.
Oral Dis ; 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36564993

RESUMO

OBJECTIVES: To analyze the clinicopathological features, locoregional or distant metastasis, and prognosis of adenoid cystic carcinoma of submandibular gland (SMG-AdCC). METHODS: The clinicopathological data of 80 patients with SMG-AdCC from January 2005 to December 2017 were analyzed retrospectively, and the relationships between different parameters of SMG-AdCC and its locoregional or distant metastasis or prognosis were analyzed. RESULTS: As of December 2019, 41 patients (51.25%) were tumor-free, while 20 patients were found to be living with tumors. The locoregional metastasis rate of grade II-III SMG-AdCC were found to be significantly higher than that of grade I. The five-year DFS and OS rates were 70.8% and 87.1%, respectively. Univariate analysis showed that clinical size, extraglandular extension, pathological grade, pathological node (pN) status, and perineural invasion were correlated with DFS. Multivariate Cox regression analysis showed that pathological grade and extraglandular extension were independent prognostic factors for DFS; pN status and extraglandular extension were independent prognostic factors impacting OS. CONCLUSION: The pathological grade is a risk factor for locoregional metastasis of SMG-AdCC. Pathological grade, pN status, and status of extraglandular extension are independent prognostic factors for DFS/OS in SMG-AdCC patients.

7.
Eur J Neurosci ; 53(4): 1350-1361, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33052619

RESUMO

To explore the clinical characteristics and prognosis of COVID-19 patients with cerebral stroke. A total of 2,474 COVID-19 patients from February 10th to March 24th, 2020 were admitted and treated in two branches (Optic Valley and Sino-French New City branch) of the Tongji Hospital. Data on the clinical characteristics, laboratory parameters and prognosis of COVID-19 patients with or without cerebral stroke were collected and comparatively analysed. Of the 2,474 COVID-19 patients, 113 (4.7%) patients had cerebral stroke and 25 (1.0%) patients had new-onset stroke. Eighty-eight (77.9%) patients in the previous-stroke group had cerebral ischaemia, while 25 (22.1%) patients in the new-onset stroke group had cerebral ischaemia. Most COVID-19 patients with stroke were elderly with more comorbidities such as hypertension, diabetes and heart diseases than patients without stroke. Laboratory examinations showed hypercoagulation and elevated serum parameters such as IL-6, cTnI, NT pro-BNP and BUN. Consciousness disorders, a long disease course and poor prognosis were also more commonly observed in stroke patients. The mortality rate of stroke patients was almost double (12.4% vs. 6.9%) that of patients without stroke. In addition, age, male sex and hypertension were independent predictors for new cerebral stroke in COVID-19 patients. In conclusion, the high risk of new-onset stroke must be taken into consideration when treating COVID-19 patients with an elderly age combined with a history of hypertension. These patients are more vulnerable to multiorgan dysfunction and an overactivated inflammatory response, in turn leading to an unfavourable outcome and higher mortality rate.


Assuntos
COVID-19/complicações , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , Comorbidade , Feminino , Humanos , Hipertensão/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Acidente Vascular Cerebral/complicações
8.
Chem Soc Rev ; 49(11): 3484-3524, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32342064

RESUMO

The urgent need to address the high-cost issue of proton-exchange membrane fuel cell (PEMFC) technologies, particularly for transportation applications, drives the development of simultaneously highly active and durable platinum group metal-free (PGM-free) catalysts and electrodes. The past decade has witnessed remarkable progress in exploring PGM-free cathode catalysts for the oxygen reduction reaction (ORR) to overcome sluggish kinetics and catalyst instability in acids. Among others, scientists have identified the newly emerging atomically dispersed transition metal (M: Fe, Co, or/and Mn) and nitrogen co-doped carbon (M-N-C) catalysts as the most promising alternative to PGM catalysts. Here, we provide a comprehensive review of significant breakthroughs, remaining challenges, and perspectives regarding the M-N-C catalysts in terms of catalyst activity, stability, and membrane electrode assembly (MEA) performance. A variety of novel synthetic strategies demonstrated effectiveness in improving intrinsic activity, increasing active site density, and attaining optimal porous structures of catalysts. Rationally designing and engineering the coordination environment of single metal MNx sites and their local structures are crucial for enhancing intrinsic activity. Increasing the site density relies on the innovative strategies of restricting the migration and agglomeration of single metal sites into metallic clusters. Relevant understandings provide the correlations among the nature of active sites, nanostructures, and catalytic activity of M-N-C catalysts at the atomic scale through a combination of experimentation and theory. Current knowledge of the transferring catalytic properties of M-N-C catalysts to MEA performance is limited. Rationally designing morphologic features of M-N-C catalysts play a vital role in boosting electrode performance through exposing more accessible active sites, realizing uniform ionomer distribution, and facilitating mass/proton transports. We outline future research directions concerning the comprehensive evaluation of M-N-C catalysts in MEAs. The most considerable challenge of current M-N-C catalysts is the unsatisfied stability and rapid performance degradation in MEAs. Therefore, we further discuss practical methods and strategies to mitigate catalyst and electrode degradation, which is fundamentally essential to make M-N-C catalysts viable in PEMFC technologies.

9.
Cardiology ; 145(4): 203-214, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069453

RESUMO

BACKGROUND: The clinical condition of hypertrophic obstructive cardiomyopathy (HOCM) and concomitant systemic hypertension is growing more and more prevalent, and it brings about a challenging diagnostic and therapeutic dilemma. However, whether systemic hypertension has an impact on HOCM, and whether sex-related differences exist in this impact, remains unclear. METHODS: A total of 453 HOCM patients (age 48.7 ± 12.8 years, 252 [55.6%] males) were recruited in this study. There were 150 patients (33.1%, 81 males and 69 females) with a history of controlled systemic hypertension. Cardiac magnetic resonance (CMR) imaging was performed in all patients. Left ventricular (LV) remodeling index (LVRI) was determined by CMR. LVRI >1.3 g/mL was defined as pathological LV remodeling. RESULTS: Men had significantly greater LVRI (1.40 ± 0.54 vs. 1.15 ± 0.38 g/mL, p < 0.001) and LVRI >1.3 g/mL (p = 0.002), compared with women. The incidence of syncope and 5-year sudden cardiac death risk score were significantly lower in HOCM with hypertension than those without hypertension. LVRI (p = 0.003) and LVRI >1.3 g/mL (p = 0.007) were significantly smaller in males with hypertension, but not in females with hypertension. However, log cardiac troponin I and log N-terminal pro-B-type natriuretic peptide were positively correlated with LVRI in men and women. On multivariable logistic analysis, hypertension (OR 0.172, 95% CI 0.056-0.528, p = 0.002) remained an independent determinant of pathological LV remodeling in males, whereas not in females. CONCLUSIONS: There were significant sex differences in the impact of systemic hypertension on LV remodeling in patients with HOCM. Controlled systemic hypertension may contribute to improving LV remodeling in male patients with HOCM, but not in females.


Assuntos
Cardiomiopatia Hipertrófica , Hipertensão , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Remodelação Ventricular
10.
BMC Cardiovasc Disord ; 20(1): 136, 2020 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32169036

RESUMO

BACKGROUND: Coronary artery fistula (CAF) is an abnormal connection between a coronary artery and either a cardiac chamber or the great vessels. Although most patients are asymptomatic, potential complications such as heart failure, angina pectoris or acute myocardial infarction can be fatal. CASE PRESENTATION: We present here a 62-year-old man diagnosed with giant coronary artery fistula complicated with gross coronary artery aneurysm and acute myocardial infarction. He underwent intravenous thrombolysis treatment at a local hospital, coronary angiography at a regional hospital and complex surgery at a national centre for cardiovascular disease. The patient had no major adverse cardiac events during the 3-year follow-up. CONCLUSION: Early diagnosis of CAF patients and an appropriate treatment plan are the key factors for avoiding serious complications. Because of the rare incidence of this disease, it is necessary to discover and discuss management strategies, including medical management, percutaneous interventions or surgical treatment, for a successful outcome.


Assuntos
Aneurisma Coronário/etiologia , Anomalias dos Vasos Coronários/complicações , Infarto do Miocárdio/etiologia , Fístula Vascular/complicações , Procedimentos Cirúrgicos Cardíacos , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/cirurgia , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/cirurgia
11.
Heart Vessels ; 35(6): 876-885, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31907598

RESUMO

As highly sensitive and specific markers of myocardial damage, cardiac troponins were demonstrated to correlate with clinical parameters of patients with hypertrophic cardiomyopathy. However, the relationship between cardiac troponins and presence of non-sustained ventricular tachycardia (NSVT) in hypertrophic cardiomyopathy remains unclear. The aim of our study was to explore the association between serum cardiac troponin I (cTNI) and presence of NSVT in patients with hypertrophic obstructive cardiomyopathy (HOCM). A total of 309 HOCM patients were enrolled in our study. All participants underwent clinical evaluations, including collections of medical history, blood tests, 24-h Holter monitoring, echocardiography, and cardiac magnetic resonance imaging. There were 53 (17.2%) patients with NSVT and 256 patients without it. Compared to patients without NSVT, serum cTNI (P < 0.001) and plasma NT-proBNP (P = 0.042) were significantly higher in patients with NSVT. Moreover, cTNI and NT-proBNP were positively correlated with left atrial diameter, maximum wall thickness (MWT), left ventricular volume index and left ventricular mass index. In multivariable logistic analysis, log cTNI [odds ratio (OR) = 2.408, 95% confidence interval (CI) 1.108-5.325, P = 0.027], left ventricular end-diastole diameter (OR = 0.922, 95%CI 0.856-0.994, P = 0.034), MWT (OR = 1.131, 95%CI 1.035-1.235, P = 0.006) and left ventricular end-systole volume index (OR = 1.060, 95%CI 1.025-1.096, P = 0.001) were independent determinants of NSVT occurrence after adjustment for potential cofounders. Serum cTNI level was elevated in patients with NSVT. And it was independently associated with NSVT in patients with HOCM. Our results suggest that it may be more reasonable for HOCM patients with elevated serum cTNI to extend the time of Holter monitoring.


Assuntos
Cardiomiopatia Hipertrófica/sangue , Taquicardia Ventricular/sangue , Troponina I/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologia , Regulação para Cima
12.
Heart Vessels ; 35(1): 78-85, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31250132

RESUMO

Lymphatic microvessel density (LMVD) contributes to fibrosis in patients with myocardial infarction. However, the role of LMVD in the process of myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) patients is unclear. We studied LMVD in ventricular septal (VS) samples from 52 individuals (42 was HOCM patients who underwent a transaortic extended septal myectomy, and 10 traffic accident victims), and examined the relationships between the LMVD stained immunohistochemically with lymphatic vessel endothelial hyaluronan receptor (LYVE-1) antibodies, collagen volume fraction (CVF), and clinical characteristics. Compared with traffic accident victims, LMVD was significantly increased in VS of HOCM patients (132.0 ± 49.0 VS 57.8 ± 48.8/mm2, p = 0.000). HOCM patients with syncope had higher level of LMVD than without syncope [166.7 (131.0-201.1) VS 116.4 (80.7-152.1)/mm2, p = 0.017], and LMVD were positively correlated with Log (CVF) (r = 0.431, p = 0.004). On multiple variables regression analysis, LMVD was independently associated with Log (CVF) (r = 0.379, p = 0.009) and syncope (r = 0.335, p = 0.020). In conclusions, the LYVE-1-positive lymphatics have close associations with VS fibrosis in HOCM patients.


Assuntos
Cardiomiopatia Hipertrófica/metabolismo , Linfangiogênese , Vasos Linfáticos/química , Septo Interventricular/química , Proteínas de Transporte Vesicular/análise , Adulto , Biomarcadores/análise , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Estudos de Casos e Controles , Feminino , Fibrose , Humanos , Vasos Linfáticos/patologia , Vasos Linfáticos/fisiopatologia , Masculino , Pessoa de Meia-Idade , Síncope/etiologia , Regulação para Cima , Septo Interventricular/patologia , Septo Interventricular/fisiopatologia
13.
Angew Chem Int Ed Engl ; 59(48): 21698-21705, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-32820860

RESUMO

Atomically dispersed and nitrogen coordinated single metal sites (M-N-C, M=Fe, Co, Ni, Mn) are the popular platinum group-metal (PGM)-free catalysts for many electrochemical reactions. Traditional wet-chemistry catalyst synthesis often requires complex procedures with unsatisfied reproducibility and scalability. Here, we report a facile chemical vapor deposition (CVD) strategy to synthesize the promising M-N-C catalysts. The deposition of gaseous 2-methylimidazole onto M-doped ZnO substrates, followed by an in situ thermal activation, effectively generated single metal sites well dispersed into porous carbon. In particular, an optimal CVD-derived Fe-N-C catalyst exclusively contains atomically dispersed FeN4 sites with increased Fe loading relative to other catalysts from wet-chemistry synthesis. The catalyst exhibited outstanding oxygen-reduction activity in acidic electrolytes, which was further studied in proton-exchange membrane fuel cells with encouraging performance.

14.
Biochem Biophys Res Commun ; 508(1): 66-71, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30471855

RESUMO

Mucoepidermoid carcinoma (MEC) of salivary gland is a disease characterized by high rate of diatant metastasis, and associated with poor outcomes. However, the molecular mechanisms underlying the MEC remain poorly understand. Here, we simultaneously detected, for the first time, the expression profiles of mRNAs, lncRNAs, and circRNAs in four pairs of MEC and matched non-carcinoma tissues by microarrays. A total of 3612 mRNA, 3091 lncRNAs, and 284 circRNAs were altered during the pathogenesis of MEC. The functions of these differentially expressed RNAs were predicted by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Co-expression networks of lncRNA-mRNA and circRNA-miRNA were conducted to uncovered the hidden ceRNA mechanisms. Moreover, NONHSAT154433.1 that associated with ADAM12 and hsa_circ_0012342 were further screened and confirmed using qRT-PCR analysis. In conclusion, this study provides a systematic perspective on the potential function of non-coding RNAs (ncRNAs) in the molecular mechanisms of MEC. Among these, NONHSAT154433.1 and hsa_circ_0012342 might be served as potential prognostic biomarkers and therapeutic target of MEC.


Assuntos
Carcinoma Mucoepidermoide/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA/genética , Neoplasias das Glândulas Salivares/genética , Sequência de Bases , Sítios de Ligação/genética , Carcinoma Mucoepidermoide/metabolismo , Biologia Computacional , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Marcadores Genéticos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , RNA/metabolismo , RNA Circular , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Neoplasias das Glândulas Salivares/metabolismo
15.
PLoS Genet ; 12(3): e1005910, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27010727

RESUMO

Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10(-8)), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.


Assuntos
Citocromo P-450 CYP2B6/genética , Proteínas da Matriz Extracelular/genética , Dependência de Heroína/genética , Metadona/administração & dosagem , Adulto , Androstanos/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Haplótipos/genética , Heroína/metabolismo , Heroína/toxicidade , Dependência de Heroína/metabolismo , Dependência de Heroína/patologia , Humanos , Masculino , Metadona/metabolismo , Pessoa de Meia-Idade , Tratamento de Substituição de Opiáceos , Farmacogenética , Polimorfismo de Nucleotídeo Único , Estereoisomerismo
16.
Cell Physiol Biochem ; 50(1): 317-331, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30282066

RESUMO

BACKGROUND/AIMS: Protein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase that mediates cell cycle regulation and metabolism. Mounting evidence has indicated that PP2A inhibition exhibits considerable anticancer potency in multiple types of human cancers. However, the efficacy of PP2A inhibition remains unexplored in mucoepidermoid carcinoma (MEC), especially in locally advanced and metastatic cases with limited systemic treatment. In this study, we demonstrated the therapeutic potency of LB100 in mucoepidermoid carcinoma. METHODS: In this study, the expression of PP2A was evaluated using immunohistochemical (IHC) staining. The effects associated with LB100 alone and in combination with cisplatin for the treatment of mucoepidermoid carcinoma were investigated both in vitro, regarding metabolism, proliferation, and migration, and in vivo in a mucoepidermoid carcinoma xenograft model. In addition, with LB100 treatment and in response to an insulin stimulus, the expression levels and phosphorylation levels of targets in the PI3K-AKT pathway were determined using western blot analysis and immunoblotting. RESULTS: The expression of protein phosphatase 2A was significantly upregulated in the clinical specimens of high-grade MECs compared with those of low-/medium-grade MECs and normal controls. In this article, we report that a small molecule PP2A inhibitor, LB100, decreased cellular viability and glycolytic activity and induced G2/M cell cycle arrest. Importantly, LB100 enhanced the efficacy of cisplatin in mucoepidermoid carcinoma cells both in vitro and in vivo. PP2A inhibition by LB100 increased the phosphorylation of insulin receptor substrate 1(IRS-1) on serine residues, downregulated the expression of phosphatidylinositol 3-kinase (PI3K) p110 alpha subunit and dephosphorylated AKT at Ser473 and Thr308 in mucoepidermoid carcinoma cells in response to insulin stimulus. CONCLUSION: These results highlight the translational potential of PP2A inhibition to synergize with cisplatin in mucoepidermoid carcinoma treatment.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Carcinoma Mucoepidermoide/patologia , Insulina/metabolismo , Piperazinas/farmacologia , Proteína Fosfatase 2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adulto , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Mucoepidermoide/tratamento farmacológico , Carcinoma Mucoepidermoide/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Feminino , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Fosfatase 2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo
17.
Cardiology ; 141(4): 202-211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30820009

RESUMO

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is a myocardial disease characterized by fibrosis and microvascular ischemia. Microvessels play a critical role in myocardial fibrosis in HOCM. However, it remains unclear whether or not myocardial fibrosis is associated with microvascular density (MVD) changes. OBJECTIVE: The aim of the present study was to investigate whether a reduction in MVD is related to myocardial fibrosis in HOCM cardiac samples. METHODS: We analyzed MVD and fibrosis in myectomy left ventricular (LV) septal wall specimens from 53 HOCM patients. Control myocardium from the LV septal wall was collected at autopsy of 9 individuals who died of noncardiac causes. RESULTS: The fibrosis ratio (% area) in HOCM was higher and the MVD was lower than that in control subjects (i.e., 12.7 ± 10.0 vs. 4.0 ± 1.4%, p = 0.012, and 480.9 ± 206.7 vs. 1,425 ± 221/mm2, p < 0.001). Patients with mild fibrosis had a higher MVD than patients with moderate fibrosis (i.e., 568.2 ± 214.8 vs. 403.2 ± 167.8/mm2, p = 0.006) and patients with severe fibrosis (i.e., 568.2 ± 214.8 vs. 378.6 ± 154.0/mm2, p = 0.024). Furthermore, a significant negative correlation was found between myocardial fibrosis and MVD in HOCM patients (r = -0.40, p = 0.003), which was also found in mild fibrosis (r = -0.40, p = 0.043), moderate fibrosis (r = -0.50, p = 0.024), and severe fibrosis (r = -0.24, p = 0.61), although no significant differences were observed in severe fibrosis. Additionally, we demonstrated that late gadolinium enhancement was negatively correlated with MVD (r = -0.37, p = 0.03) and positively correlated with fibrosis (r = 0.44, p = 0.01). CONCLUSION: HOCM patients had a higher myocardial fibrosis ratio and a lower MVD. The severity of myocardial fibrosis was negatively correlated with MVD in HOCM. These findings showed that a reduced MVD may contribute to myocardial fibrosis in HOCM.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Septos Cardíacos/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Rarefação Microvascular/diagnóstico por imagem , Miocárdio/patologia , Adulto , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/patologia , Meios de Contraste , Ecocardiografia , Feminino , Fibrose , Gadolínio DTPA , Septos Cardíacos/patologia , Humanos , Masculino , Rarefação Microvascular/etiologia , Rarefação Microvascular/patologia , Pessoa de Meia-Idade , Contração Miocárdica
18.
BMC Cardiovasc Disord ; 18(1): 207, 2018 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390664

RESUMO

BACKGROUND: Atrial fibrillation (AF) is the most common complication in hypertrophic cardiomyopathy (HCM). The mechanisms of AF is associated with left atrial (LA) structural remodeling in HCM patients. However, the impact of left ventricular (LV) remodeling on the presence of AF in HCM patients has not been evaluated yet. We sought to investigate effect of LV remodeling on the presence of AF assessed by cardiovascular magnetic resonance (CMR) in HCM patients. METHODS: A total of 394 HCM patients were enrolled into this study, including HOCM patients (n = 293) and NOHCM patients (n = 101). Patients were divided into HCM with AF (50) and HCM without AF (n = 344). Data were collected from hospital records. RESULTS: LA diameter and LV remodeling index (LVRI) were significantly higher in HCM patients with AF than that of HCM patients without AF (46.6 ± 7.4 mm versus 39.9 ± 8.0 mm, p < 0.001, and 1.46 ± 0.6 versus 1.2 ± 0.4, p = 0.002, respectively). HCM patients with AF were older than HCM patients without AF (53.6 ± 11.7 years versus 47.7 ± 13.6 years, p = 0.002). Additionally, LVRI positively correlated to LA size (r = 0.12, p = 0.02). In a multivariable logistic regression analysis, when adjusting for age and LV end diastolic mass index, LVRI and LA size remained an independent determinant of AF in HCM patients (OR = 4.7, p = 0.001 and OR = 1.13, P < 0.001). CONCLUSION: HCM patients with AF showed significantly more LA diameter, LVRI and age than HCM patients without AF. LVRI and LA size were strong independent predictor of AF in HCM, suggesting LV remodeling may contribute to the occurrence of AF in HCM patients.


Assuntos
Fibrilação Atrial/etiologia , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo , Remodelamento Atrial , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Ecocardiografia Doppler em Cores , Eletrocardiografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
19.
J Oral Maxillofac Surg ; 76(10): 2241.e1-2241.e8, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29106891

RESUMO

Adult rhabdomyomas (ARMs) are rare solitary benign neoplasms of the head and neck, and multifocal ARMs are even rarer. Owing to the low incidence and scanty knowledge of this peculiar entity, several patients have been reported to be misdiagnosed or overtreated. This report describes a patient with multifocal ARMs with as many as 10 synchronous lesions. In addition, all published cases of this entity in PubMed, Embase, and Web of Science databases were reviewed up to March 1, 2017. Overall, 10 of 29 reported cases had more than 2 lesions, with a maximum of 10 synchronous masses in the present report. Multifocal ARMs usually present as slow-growing lumps in the parapharyngeal region, with a predilection for older men. Treatments of multifocal ARMs should be tailored and close follow-up is recommended for tiny lesions located in vital structures. In addition, multifocal ARMs should be differentially diagnosed from other multifocal lesions in the head and neck region to avoid aggressive excision and produce a favorable outcome for patients.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Rabdomioma/cirurgia , Idoso , Meios de Contraste , Diagnóstico Diferencial , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Rabdomioma/diagnóstico por imagem , Rabdomioma/patologia
20.
Jpn J Clin Oncol ; 47(6): 505-511, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28334798

RESUMO

OBJECTIVE: Postoperative delirium is common after extensive surgery. This study aimed to collate and synthesize published literature on risk factors for delirium in patients with head and neck cancer surgery. METHODS: Three databases were searched (MEDLINE, Embase, and Cochrane Library) between January 1987 and July 2016. The Newcastle Ottawa Scale (NOS) was adopted to evaluate the study quality. Pooled odds ratios or mean differences for individual risk factors were estimated using the Mantel-Haenszel and inverse-variance methods. RESULTS: They provided a total of 1940 patients (286 with delirium and 1654 without), and predominantly included patients undergoing head and neck cancer surgery. The incidence of postoperative delirium ranged from 11.50% to 36.11%. Ten statistically significant risk factors were identified in pooled analysis. Old age, age >70 years, male sex, duration of surgery, history of hypertension, blood transfusions, tracheotomy, American Society of Anesthesiologists physical status grade at least III, flap reconstruction and neck dissection were more likely to sustain delirium after head and neck cancer surgery. CONCLUSION: Delirium is common in patients undergoing major head neck cancer surgery. Several risk factors were consistently associated with postoperative delirium. These factors help to highlight patients at risk of developing delirium and are suitable for preventive action.


Assuntos
Delírio/epidemiologia , Delírio/etiologia , Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
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