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1.
Circ Cardiovasc Interv ; 17(5): e013579, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38629273

RESUMO

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post-LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post-LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787-1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17-8.83]; P=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06-1.17]; P=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29-10.42]; P=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71-8.07]; P=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28-10.09]; P=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post-LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03788941.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Cateterismo Cardíaco , Angiografia por Tomografia Computadorizada , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Apêndice Atrial/fisiopatologia , Apêndice Atrial/diagnóstico por imagem , Masculino , Feminino , Idoso , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/mortalidade , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Fibrilação Atrial/diagnóstico por imagem , Estudos Prospectivos , Fatores de Risco , Ataque Isquêmico Transitório/etiologia , Fatores de Tempo , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Medição de Risco , Hemorragia , Desenho de Prótese
2.
BMC Health Serv Res ; 24(1): 67, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216934

RESUMO

BACKGROUND: The growing demand for electrophysiology (EP) treatment in China presents a challenge for current EP care delivery systems. This study constructed a discrete event simulation (DES) model of an inpatient EP care delivery process, simulating a generalized inpatient journey of EP patients from admission to discharge in the cardiology department of a tertiary hospital in China. The model shows how many more patients the system can serve under different resource constraints by optimizing various phases of the care delivery process. METHODS: Model inputs were based on and validated using real-world data, simulating the scheduling of limited resources among competing demands from different patient types. The patient stay consists of three stages, namely: the pre-operative stay, the EP procedure, and the post-operative stay. The model outcome was the total number of discharges during the simulation period. The scenario analysis presented in this paper covers two capacity-limiting scenarios (CLS): (1) fully occupied ward beds and (2) fully occupied electrophysiology laboratories (EP labs). Within each CLS, we investigated potential throughput when the length of stay or operative time was reduced by 10%, 20%, and 30%. The reductions were applied to patients with atrial fibrillation, the most common indication accounting for almost 30% of patients. RESULTS: Model validation showed simulation results approximated actual data (137.2 discharges calculated vs. 137 observed). With fully occupied wards, reducing pre- and/or post-operative stay time resulted in a 1-7% increased throughput. With fully occupied EP labs, reduced operative time increased throughput by 3-12%. CONCLUSIONS: Model validation and scenario analyses demonstrated that the DES model reliably reflects the EP care delivery process. Simulations identified which phases of the process should be optimized under different resource constraints, and the expected increases in patients served.


Assuntos
Fibrilação Atrial , Humanos , Simulação por Computador , Centros de Atenção Terciária , Eletrofisiologia , China
3.
Int J Cardiol ; 397: 131640, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38065326

RESUMO

BACKGROUND: The residual device patency (RDP) after left atrial appendage closure (LAAC) with the LACbes device has not been specifically explored in atrial fibrillation (AF) patients. This study aims to explore the incidence, impact and predictors of RDP detected by cardiac computed tomography angiography (CCTA) post LAAC. METHODS: AF patients implanted with the LACbes device were prospectively enrolled. CCTA device surveillance was performed at 3 months post-procedure. Major adverse events (MAEs), including stroke/transient ischemic attack, major bleeding and all-cause death, were evaluated. RESULTS: Among 141 patients with CCTA surveillance, 56 (39.7%) showed no visible leak and 85 (60.3%) showed RDP. During the median follow-up of 443 [232, 706] days, the presence of RDP was not associated with an increased risk of MAEs (adjusted hazard ratio [HR]: 4.07, 95% confidence interval [CI]: 0.49-34.24, p = 0.196), while peri-device leak (PDL) at the lobe was associated with heightened risks of MAEs (adjusted HR: 6.85, 95% CI: 1.62-28.89, p = 0.009). In patients with PDL at the lobe, antiplatelet after 6 months (HR: 0.20, 95% CI: 0.05-0.91, p = 0.038) was independent protective predictor of MAEs. Besides, current smoking (odds ratio [OR]: 7.52, 95% CI: 2.68-21.08, p < 0.001) and maximum diameter of LAA orifice (OR: 1.16, 95% CI: 1.00-1.34, p = 0.048) were independent predictors of PDL at the lobe. CONCLUSIONS: Presence of PDL at the device lobe detected by CCTA at 3-month post LAAC with LACbes is associated with unfavorable prognosis in AF patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03788941.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Cateterismo Cardíaco , Ecocardiografia Transesofagiana , Incidência , Oclusão do Apêndice Atrial Esquerdo , Próteses e Implantes/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento
4.
Am J Cardiol ; 204: 312-319, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37567023

RESUMO

Left atrial appendage closure (LAAC) proved to be noninferior to oral anticoagulation (OAC) in nonablated patients with atrial fibrillation (AF). This study aimed to compare the efficacy and safety of LAAC with those of OAC therapy in patients after AF ablation. This study included patients who underwent catheter ablation (CA) of AF between January 2016 and December 2020. The cohort was divided into CA + LAAC and CA + OAC, where propensity score matching was used to select controls, and each group contained 682 subjects. The enrolled patients' mean age was 70.34 ± 8.32 years, and 47.3% were female; their CHA2DS2-VASc score was 3.48 ± 1.17. Baseline characteristics were similar between groups. After a 3-year mean follow-up, the incidence of thromboembolic events was 1.25 and 1.10 and that of major bleeding events was 0.65 and 1.72 per 100 patient-years in the CA + LAAC, and CA + OAC groups, respectively. The rate of thromboembolisms and major adverse cardiovascular events was similar between the 2 groups (hazard ratio [HR] 1.162, 95% confidence interval [CI] 0.665 to 2.030, p = 0.598, HR 0.711, 95% CI 0.502 to 1.005, p = 0.053); however, that of major bleeding and all-cause death was significantly reduced with LAAC (HR 0.401, 95% CI 0.216 to 0.746, p = 0.004, HR 0.528, 95% CI 0.281 to 0.989, p = 0.046). There was no significant difference in periprocedural complications (p >0.05) and the rate of AF recurrence (OAC vs LAAC: 39.44% vs 40.62%, p = 0.658). LAAC is a reasonable and safer alternative to OAC therapy in high-risk patients after AF ablation.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Acidente Vascular Cerebral , Tromboembolia , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Apêndice Atrial/cirurgia , Hemorragia/induzido quimicamente , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Anticoagulantes/uso terapêutico , Ablação por Cateter/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
5.
Cardiovasc J Afr ; 34(4): 256-259, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36044199

RESUMO

Kounis syndrome is defined as an acute coronary syndrome (ACS) secondary to allergic or hypersensitivity reactions. It can be further categorised into subtypes such as coronary vasospasms, acute myocardial infarction or stent thrombosis based on the pathogenesis. Kounis syndrome is most likely an underdiagnosed condition in China, given the many triggers reported in the literature. Herein, we report a case of Kounis syndrome, possibly triggered by a bee sting. The patient had late onset of angina symptoms with delayed diagnosis due to unfamiliarity with this condition. In patients with clinical signs of ACS that are superimposed on a hypersensitivity reaction, especially those with pre-existing cardiovascular risk factors, Kounis syndrome should be considered, so that appropriate assessment and treatment can be initiated. Prompt management of both the allergic reaction and the ACS is vital for Kounis syndrome.


Assuntos
Síndrome Coronariana Aguda , Hipersensibilidade , Mordeduras e Picadas de Insetos , Síndrome de Kounis , Infarto do Miocárdio , Animais , Humanos , Abelhas , Síndrome de Kounis/diagnóstico , Síndrome de Kounis/etiologia , Síndrome de Kounis/terapia , Mordeduras e Picadas de Insetos/complicações , Mordeduras e Picadas de Insetos/diagnóstico , Hipersensibilidade/etiologia , Infarto do Miocárdio/complicações , Angina Pectoris , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/etiologia
6.
Oncogene ; 40(36): 5468-5481, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34290402

RESUMO

The ARID1A gene, which encodes a subunit of the SWI/SNF chromatin remodeling complex, has been found to be frequently mutated in many human cancer types. However, the function and mechanism of ARID1A in cancer metastasis are still unclear. Here, we show that knockdown of ARID1A increases the ability of breast cancer cells to proliferate, migrate, invade, and metastasize in vivo. The ARID1A-related SWI/SNF complex binds to the second exon of CDH1 and negatively modulates the expression of E-cadherin/CDH1 by recruiting the transcriptional repressor ZEB2 to the CDH1 promoter and excluding the presence of RNA polymerase II. The silencing of CDH1 attenuated the migration, invasion, and metastasis of breast cancer cells in which ARID1A was silenced. ARID1A depletion increased the intracellular enzymatic processing of E-cadherin and the production of C-terminal fragment 2 (CTF2) of E-cadherin, which stabilized ß-catenin by competing for binding to the phosphorylation and degradation complex of ß-catenin. The matrix metalloproteinase inhibitor GM6001 inhibited the production of CTF2. In zebrafish and nude mice, ARID1A silencing or CTF2 overexpression activated ß-catenin signaling and promoted migration/invasion and metastasis of cancer cells in vivo. The inhibitors GM6001, BB94, and ICG-001 suppressed the migration and invasion of cancer cells with ARID1A-deficiency. Our findings provide novel insights into the mechanism of ARID1A metastasis and offer a scientific basis for targeted therapy of ARID1A-deficient cancer cells.


Assuntos
Antígenos CD , Caderinas , Animais , Humanos , Camundongos
7.
Nanotechnology ; 29(14): 145603, 2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29384131

RESUMO

Herein we report the successful doping of tellurium (Te) into molybdenum disulfide (MoS2) monolayers to form MoS2x Te2(1-x) alloy with variable compositions via a hydrogen-assisted post-growth chemical vapor deposition process. It is confirmed that H2 plays an indispensable role in the Te substitution into as-grown MoS2 monolayers. Atomic-resolution transmission electron microscopy allows us to determine the lattice sites and the concentration of introduced Te atoms. At a relatively low concentration, tellurium is only substituted in the sulfur sublattice to form monolayer MoS2(1-x)Te2x alloy, while with increasing Te concentration (up to ∼27.6% achieved in this study), local regions with enriched tellurium, large structural distortions, and obvious sulfur deficiency are observed. Statistical analysis of the Te distribution indicates the random substitution. Density functional theory calculations are used to investigate the stability of the alloy structures and their electronic properties. Comparison with experimental results indicate that the samples are unstrained and the Te atoms are predominantly substituted in the top S sublattice. Importantly, such ultimately thin Janus structure of MoS2(1-x)Te2x exhibits properties that are distinct from their constituents. We believe our results will inspire further exploration of the versatile properties of asymmetric 2D TMD alloys.

8.
Journal of Experimental Hematology ; (6): 1657-1662, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-773040

RESUMO

OBJECTIVE@#To investigate the relationship of T lymphocyte subsets, B lymphocytes and NK cells with the genesis, progression and prognosis of B cell lymphoma.@*METHODS@#The levels of T lymphocyte subsets, B lymphocytes and NK cells in peripheral blood of healthy control group and B cell lymphoma group were detected by flow cytometry (FCM). The clinical data were collected, and the relationship of these immune indexes with the general conditions, laboratory indexes, curative effect and prognosis were analyzed.@*RESULTS@#Forty-four patients entolled in this study including 24 male and 20 females with the median age of 57 years old (17-82 years), all the patients were the first visit to our hospital and diagnosed. The total counts of lymphocytes, T, B and NK cells in the peripheral blood of patients with the first treatment of B-cell lymphoma were significantly lower than those in healthy controls, and the ratio of CD3HLA-DR activated T cells was significantly higher than that of healthy controls ( 61.5 /μl was higher than that in patients with low level of NK cells.@*CONCLUSION@#The level of total lymphocytes, total T cells, total B cells, NK cells and advanced activated T cells in the patients with B cell lymphoma were significantly different from those in normal subjects. Total count of lymphocytes, T cells, B cells, CD4 cells and NK cells in peripheral blood are important prognostic indicators for BCL. The ECOG score and β2-microglobulin level are independent risk factors for prognosis. The NK cell level and FAC-1 are independent protective factors for the prognosis of B cell lymphoma.


Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Células Matadoras Naturais , Contagem de Linfócitos , Linfoma de Células B , Prognóstico , Subpopulações de Linfócitos T
9.
Journal of Experimental Hematology ; (6): 1336-1342, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-689934

RESUMO

<p><b>OBJECTIVE</b>To analyse the clinical characteristics and therapeutic efticacy of patients with mantle cell lymphoma(MCL).</p><p><b>METHODS</b>The clinical data including cliniced parameters and laboratorial test results of 54 patients with MCL were collected and restrospectively analyzed to clarity the clinical characteristics of MCL and to evaluate the survival and factors affecting prgnosis of patients.</p><p><b>RESULTS</b>The incidence of MCL accounted for 4.0% of NHL in our center. The median age of MCL patients was 63 years old, the male and female ratio was 1.4∶1. The MCL patients inⅢ-Ⅳ stage accounted for 96.3%; the extranodal organ involvement existed in 98.1% patients, the most common extranodal involvement sites were bone marrow(72.2%), spleen(51.9%), gastrointestinal tract(25.9%). The overall response rate(ORR) was 66.7%, among which the complete remisson (CR) rate was 37.1%, 3 year and 5 year-progression free survival rate was 52.7% and 34.7% respectively, 3 year and 5 year overall survival rate was 60.4% and 49.6% respectively. The therapeutic efficacy in chemotherapy combined with cytarabine group was suprior to that in chemotherapy group without cyteratine, the chemotherapy comtined with auto-HSCT could further improve the prognosis of patients. The unvariatc analysis showed that the KI67 level, B sgmptom, liver function, LDH and C-RP levels, initial therapeutic efficacy, high dose cytarabine regimen, auto-HSCT and relapse-refractroy status were prognosis-related factors; the multi-variate analysis showed that the initial therapeutic efficacy and relapse rcfractory stasus were independent prognostic risk factors. Analysis showed that the surival of patients stratified according to MIPI and MIPI-c indexes was significantly different from that stratified by IPI index.</p><p><b>CONCLUSION</b>The MCL patients commonly complicated by extranodal involvement and have poor prognoss. Using the chenotherapy regimen combined with high doge of cytarabine as induction therapy and auto-HSCT as consotidatory therapy shows the significont efficacy for survival of young patients with MCL. The MIPI and MIPIc indexe are more much suitable for prognosis evaluation of MCL patients.The initial therapeuntic efficacy and relapse-refractrong status are the independant prognosis-related factors.</p>

10.
Chinese Pharmacological Bulletin ; (12): 959-963, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-705159

RESUMO

Aim To observe the expression of FN and TGF-β1 in the glomerular mesangial cells induced by high-glucose after the intervention of resveratrol, and further discuss its influence on SphK1/AP-1 signaling pathway. Methods The rat glomerular mesangial cells induced by high glucose were used to observe the effects of resveratrol on cell proliferation after interven-tion. The survival vitality and proliferation of glomeru-lar mesangial cells were determined by MTT, and then FN, TGF-β1 and SphK1 protein expression were deter-mined by Western blot. Also, AP-1 activity was deter- mined by EMSA assay. Results Resveratrol could obviously inhibit the proliferation of high glucose-in-duced glomerular mesangial cells, lower SphK1 expres-sion, inhibit AP-1 activity and thus inhibit the expres-sion of FN, TGF-β1. Conclusions Resveratrol inhib-its the proliferation of high glucose-induced glomerular mesangial cells, which may be closely related to the in-hibition of SphK1/AP-1 signaling pathway.

11.
Zhongguo Zhong Yao Za Zhi ; 42(7): 1390-1394, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29052404

RESUMO

To discuss the effects of total glucosides from white paeony on preventing and treating radioactive liver damage, and explore its possible mechanisms. Thirty-six patients with primary hepatic carcinoma from 105th Hospital of Chinese PLA were treated with 3-dimensional conformal radiotherapy and randomly divided into simple irradiation group, total glucosides from white paeony group, and control group. The levels of AST, ALT, HA, LN, PCⅢ, CIV and TGF-ß1 in serum of various groups were determined by using ELISA method. As compared with the simple irradiation group and control group, total glucosides from white paeony could obviously decrease the levels of AST, ALT, HA, LN, PCⅢ, CIV and TGF-ß1(P<0.05, P<0.01). The results showed that the total glucosides from white paeony could effectively prevent and treat radioactive liver damage, and its mechanism might be associated with decreasing the levels of TGF-ß1, and inhibiting the synthesis of collagen synthesis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glucosídeos/farmacologia , Fígado/efeitos da radiação , Paeonia/química , Lesões por Radiação/tratamento farmacológico , Humanos , Fígado/efeitos dos fármacos , Fator de Crescimento Transformador beta1/sangue , Resultado do Tratamento
12.
Small ; 13(12)2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28112865

RESUMO

2D black phosphorus (BP) and rhenium dichalcogenides (ReX2 , X = S, Se) possess intrinsic in-plane anisotropic physical properties arising from their low crystal lattice symmetry, which has inspired their novel applications in electronics, photonics, and optoelectronics. Different from BP with poor environmental stability, ReX2 has low-symmetry distorted 1T structures with excellent stability. In ReX2 , the electronic structure is weakly dependent on layer numbers, which restricts their property tunability and device applications. Here, the properties are tuned, such as optical bandgap, Raman anisotropy, and electrical transport, by alloying 2D ReS2 and ReSe2 . Photoluminescence emission energy of ReS2(1-x) Se2x monolayers (x from 0 to 1 with a step of 0.1) can be continuously tuned ranging from 1.62 to 1.31 eV. Polarization behavior of Raman modes, such as ReS2 -like peak at 212 cm-1 , shifts as the composition changes. Anisotropic electrical property is maintained in ReS2(1-x) Se2x with high electron mobility along b-axis for all compositions of ReS2(1-x) Se2x .

13.
Small ; 12(14): 1866-74, 2016 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-26915628

RESUMO

The high-yield and scalable production of single-layer ternary transition metal dichalcogenide nanosheets with ≈66% of metallic 1T phase, including MoS(2x)Se2(1-x) and Mo(x)W(1-x)S2 is achieved via electrochemical Li-intercalation and the exfoliation method. Thin film MoS(2x)Se2(1- x) nanosheets drop-cast on a fluorine-doped tin oxide substrate are used as an efficient electrocatalyst on the counter electrode for the tri-iodide reduction in a dye-sensitized solar cell.

14.
Int Neurourol J ; 20(4): 288-295, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28043115

RESUMO

PURPOSE: Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional-an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other's expression. METHODS: This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6-72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH. RESULTS: It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats. CONCLUSIONS: Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction.

15.
Oncotarget ; 6(11): 8606-20, 2015 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-25825982

RESUMO

Cancer-associated isocitrate dehydrogenase (IDH) 1 and 2 mutations gain a new activity of reducing α-KG to produce D-2-hydroxyglutarate (D-2-HG), which is proposed to function as an oncometabolite by inhibiting α-KG dependent dioxygenases. We investigated the function of D-2-HG in tumorigenesis using IDH1 and IDH2 mutant cancer cell lines. Inhibition of D-2-HG production either by specific deletion of the mutant IDH1-R132C allele or overexpression of D-2-hydroxyglutarate dehydrogenase (D2HGDH) increases α-KG and related metabolites, restores the activity of some α-KG-dependent dioxygenases, and selectively alters gene expression. Ablation of D-2-HG production has no significant effect on cell proliferation and migration, but strongly inhibits anchorage independent growth in vitro and tumor growth in xenografted mouse models. Our study identifies a new activity of oncometabolite D-2-HG in promoting tumorigenesis.


Assuntos
Glutaratos/metabolismo , Isocitrato Desidrogenase/fisiologia , Proteínas de Neoplasias/fisiologia , Sarcoma/patologia , Animais , Adesão Celular , Divisão Celular , Linhagem Celular Tumoral , Movimento Celular , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Isocitrato Desidrogenase/deficiência , Isocitrato Desidrogenase/genética , Ácidos Cetoglutáricos/antagonistas & inibidores , Masculino , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo , Oxigenases de Função Mista/metabolismo , Mutação de Sentido Incorreto , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/genética , Proteínas Recombinantes de Fusão/metabolismo , Sarcoma/genética , Sarcoma/metabolismo , Transfecção
16.
Int J Clin Exp Med ; 8(1): 1494-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25785162

RESUMO

Endoscopic band ligation for variceal bleeding in cirrhosis has been proved its safety and efficacy. We tried to treat submucosal tumors the gastrointestinal (GI) tract by endoscopic band ligation. The aim of this study was to evaluate the efficacy and safety of endoscopic band ligation in the treatment of submucosal tumors of the GI tract. There are 29 patients (15 men, 14 women, age range: 25-67 years old) with 30 submucosal lesions of the GI tract, including 15 lesions in the esophagus, 14 lesions in the of stomach and 1 lesion in the duodenal bulb. The average maximum diameter of the lesions was 7.78 mm (range: 2.4-23.6 mm). All submucosal lesions were successfully removed by band ligation. There is no bleeding and perforation in all patients. No recurrence was observed for the one month following-up. Endoscopic band ligation promises could be considered as a safe and effective for the treatment submucosal tumors of the GI tract, especially for the diameter of tumor < 25 mm.

17.
J Med Imaging Radiat Oncol ; 59(1): 109-14, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25088249

RESUMO

INTRODUCTION: We investigated the therapeutic effects of three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolisation (TACE) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT). METHODS: Sixty-three HCC patients with PVTT were divided into two groups. Group A (30 patients) was treated with three-dimensional conformal radiotherapy followed by 2-3 series of TACE, while group B (33 patients) was only treated with TACE. RESULTS: The 1- and 2-year survival rates of group A were 62.40% and 20.81%, respectively, with a mean survival time of 13.0 months. The 1- and 2-year survival rates of group B were 56.49% and 18.83%, respectively, with a mean survival time of 9.0 months. There were significant differences between the two groups (log-rank chi-square value = 3.950, P = 0.047). CONCLUSION: Three-dimensional conformal radiotherapy combined with TACE can significantly improve clinical outcomes in patients with HCC and PVTT compared with TACE alone.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/mortalidade , Neoplasias Hepáticas/terapia , Radioterapia de Intensidade Modulada/mortalidade , Trombose Venosa/terapia , Causalidade , China/epidemiologia , Terapia Combinada/mortalidade , Comorbidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Veia Porta , Prevalência , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Trombose Venosa/mortalidade
18.
Huan Jing Ke Xue ; 35(6): 2294-9, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25158509

RESUMO

The generation and release of algal toxin Microcystin-LR (MCLR), as well as the intracellular organic chemicals were studied during the inhibition processes of Microcystis aeruginosa using hydroquinone as the inhibitor. According to the dose-effect relationship, the corresponding dosages of EC20, EC50, EC70, EC90, EC99 were added to the algae suspension. The TOC was determined by the total organic carbon analyzer, and the three-dimensional fluorescence spectrum was obtained by the fluorescence spectrophotometer. The results showed that the generation of MCLR was inhibited at EC20 and the total MCLR was 72.4%-83.0% of the control samples. Whereas the cells were stimulated to produce higher amount of MCLR, and the total MCLR was 1.77-3.13 times as high as that of the control samples at EC50-EC99. The intracellular MCLR was largely released to the water at EC70-EC99. The release of other intracellular organic chemicals mainly referred to humic-like and fulvic-like substances, which were unstable and had an obvious degradation and transformation after 6 days of cultivation.


Assuntos
Hidroquinonas/química , Microcistinas/metabolismo , Microcystis/metabolismo , Toxinas Marinhas , Microcystis/efeitos dos fármacos , Compostos Orgânicos/metabolismo
19.
Gastroenterology ; 146(5): 1397-407, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24503127

RESUMO

BACKGROUND & AIMS: The pathogenesis of intrahepatic cholangiocarcinoma (ICC), the second most common hepatic cancer, is poorly understood, and the incidence of ICC is increasing worldwide. We searched for mutations in human ICC tumor samples and investigated how they affect ICC cell function. METHODS: We performed whole exome sequencing of 7 pairs of ICC tumors and their surrounding nontumor tissues to detect somatic alterations. We then screened 124 pairs of ICC and nontumor samples for these mutations, including 7 exomes. We compared mutations in PTPN3 with tumor recurrence in 124 patients and PTPN3 expression levels with recurrence in 322 patients (the combination of both in 86 patients). The functional effects of PTPN3 variations were determined by RNA interference and transgenic expression in cholangiocarcinoma cell lines (RBE, HCCC-9810, and Huh28). RESULTS: Based on exome sequencing, pathways that regulate protein phosphorylation were among the most frequently altered in ICC samples and genes encoding protein tyrosine phosphatases (PTPs) were among the most frequently mutated. We identified mutations in 9 genes encoding PTPs in 4 of 7 ICC exomes. In the prevalence screen of 124 paired samples, 51.6% of ICCs contained somatic mutations in at least 1 of 9 PTP genes; 41.1% had mutations in PTPN3. Transgenic expression of PTPN3 in cell lines increased cell proliferation, colony formation, and migration. PTPN3(L232R) and PTPN3(L384H), which were frequently detected in ICC samples, were found to be gain-of-function mutations; their expression in cell lines further increased cell proliferation, colony formation, and migration. ICC-associated variants of PTPN3 altered phosphatase activity. Patients whose tumors contained activating mutations or higher levels of PTPN3 protein than nontumor tissues had higher rates of disease recurrence than patients whose tumors did not have these characteristics. CONCLUSIONS: Using whole exome sequencing of ICC samples from patients, we found that more than 40% contain somatic mutations in PTPN3. Activating mutations in and high expression levels of PTPN3 were associated with tumor recurrence.


Assuntos
Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/enzimologia , Movimento Celular , Proliferação de Células , Colangiocarcinoma/genética , Neoplasias Hepáticas/genética , Mutação , Recidiva Local de Neoplasia , Proteína Tirosina Fosfatase não Receptora Tipo 3/genética , Neoplasias dos Ductos Biliares/enzimologia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/enzimologia , Colangiocarcinoma/patologia , Análise Mutacional de DNA , Ativação Enzimática , Exossomos , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Invasividade Neoplásica , Fenótipo , Proteína Tirosina Fosfatase não Receptora Tipo 3/metabolismo , Interferência de RNA , Fatores de Tempo , Transfecção
20.
PLoS One ; 6(9): e24901, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21961047

RESUMO

Tetraspanin CD151 has been implicated in metastasis through forming complexes with different molecular partners. In this study, we mapped tetraspanin web proteins centered on CD151, in order to explore the role of CD151 complexes in the progression of hepatocellular carcinoma (HCC). Immunoprecipitation was used to isolate tetraspanin complexes from HCCLM3 cells using a CD151 antibody, and associated proteins were identified by mass spectrometry. The interaction of CD151 and its molecular partners, and their roles in invasiveness and metastasis of HCC cells were assayed through disruption of the CD151 network. Finally, the clinical implication of CD151 complexes in HCC patients was also examined. In this study, we identified 58 proteins, characterized the tetraspanin CD151 web, and chose integrin ß1 as a main partner to further investigate. When the CD151/integrin ß1 complex in HCC cells was disrupted, migration, invasiveness, secretion of matrix metalloproteinase 9, and metastasis were markedly influenced. However, both CD151 and integrin ß1 expression were untouched. HCC patients with high expression of CD151/integrin ß1 complex had the poorest prognosis of the whole cohort of patients. Together, our data show that CD151 acts as an important player in the progression of HCC in an integrin ß1-dependent manner.


Assuntos
Carcinoma Hepatocelular/metabolismo , Integrina beta1/metabolismo , Neoplasias Hepáticas/metabolismo , Tetraspanina 24/metabolismo , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Estudos de Coortes , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Células Hep G2 , Humanos , Imuno-Histoquímica , Integrina beta1/genética , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Prognóstico , Ligação Proteica , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetraspanina 24/genética , Análise Serial de Tecidos
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