Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 132
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
Eur J Pharmacol ; 861: 172612, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31421088

RESUMO

Denervation caused by sciatic nerve injury has brought great harm to the patients, especially denervation-induced muscle atrophy. The body stress produces a large number of Schwann cells when the sciatic nerve is injured, and the cells secrete some cytokines including ciliary neurotrophic factor (CNTF) that not only play a role in promoting the repair of sciatic nerve, but also maintain the normal physiological function of the muscles surrounding the damaged nerves. CNTF upregulates janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) signals in myoblasts, and consequently accelerates the proliferation and differentiation of myoblasts. This effect on myoblasts is the most effective way to relieve muscle atrophy. Therefore, increasing CNTF is a promising direction to improve muscle atrophy. In the present study, an oleanolic acid derivative, HA-19, increased the proliferation of Schwann cells, and elevated CNTF production of the cells. HA-19 up-regulated the phosphorylation of JAK2 and STAT3 not only by directly acting on myoblasts, but also by increasing the secretion of CNTF of Schwann cells; and consequently, promoted the proliferation and differentiation of myoblasts. In denervation-induced muscle atrophy mice model, treatment with HA-19 significantly increased the weights of tibialis anterior (TA), gastrocnemius (Gastroc.), extensor digitorum longus (EDL), soleus and quadriceps (Quad.) under atrophied state. And, very interestingly, these muscles under normal condition were also strengthened by HA-19. Our finding demonstrated that HA-19 has a great potential as a lead compound for the drug discovery of anti-denervation-induced muscle atrophy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31430213

RESUMO

Purpose: To determine whether covered or uncovered stent insertion achieved better clinical efficacy when used to treat malignant superior vena cava (SVC) obstruction (SVCO). Material and methods: A total of 64 patients with malignant SVCO underwent stent insertion between January 2011 and March 2018 at our center. Of these, 34 were treated via uncovered stent insertion while 30 were treated via covered stent insertion. We compared the clinical effectiveness, patency of the stent, and overall survival between these two groups. Results: Both treatments achieved a 100% technical and clinical success rate, without any incidence of complications relating to the procedure. Stent dysfunction was found in one and six patients in the covered and uncovered groups during the follow-up period (1/30 vs. 6/34, p = .153), respectively. The covered stent patency period was significantly longer in the group treated with covered stents (374 vs. 317 days, p = .049), while median survival following stent insertion was 175 and 159 days, respectively, for the covered and uncovered groups (p = .784). Conclusion: Uncovered and covered stent insertion are both safe means of effectively treating patients with malignant SVCO, but covered stents achieve better patency for long-term periods than uncovered stents.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1053-1057, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418356

RESUMO

OBJECTIVE: To investigate the relationship of PTEN/PI3K/AKT signaling pathway protein expression with apoptosis and drug-resistance of children's ALL primary cells treated with daunorubicin (DNR). METHODS: The bone marrow mononuclear cells in newly diagnosed and untreated B-ALL children were collected and cultured. After the treatment of primary-cultured cells with DNR of final concentration 0.5 mg/L for 24 h, the cell apoptosis rate was detected by using cell apoptosis assay kit; the samples were collected at the on test of culture and after drug treatment, then expression levels of PTEN, PI3K and AKT proteins were detected by Western blot, moreover the interindex correlation was analyzed. RESULTS: After DNR treatment, the apoptosis rate in PTEN low expression group was lower than that in PTEN high expression group (P<0.05), showing high positive correlation of the cell apoptosis rate with the expression of PTEN before DNR treatment; the cell apoptosis rate in PI3K and AKT low expression group was higher than that in PI3K and AKT high expression group (P<0.01); however, the expression of PI3K and AKT proteins was down-regulated after treatment with DNR (P<0.01). CONCLUSION: The difference of PTEN expression is present in primary cells of B-ALL children, however the change of PTEN expression is not significant after DNR treatment, suggesting that the PTEN expression correlates with DNR-resistance. The DNR can induce the apoptosis of childrens B-ALL primary cells by down-regulating the expression of PI3K and AKT signaling pathway proteins.


Assuntos
Transdução de Sinais , Apoptose , Criança , Daunorrubicina , Humanos , PTEN Fosfo-Hidrolase , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
4.
Toxicol Appl Pharmacol ; 378: 114625, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31201822

RESUMO

Muscle atrophy refers to a decrease in the size of muscles in the body, occurs in certain muscles with inactivity in many diseases and lacks effective therapies up to date. Natural products still play an important role in drug discovery. In the present study, derivatives of a natural product, oleanolic acid, were screened with myoblast differentiation and myotube atrophy assays, respectively. Results revealed that one of the derivatives, HA-19 showed the most potent anti-muscle atrophy activity, and was used for further studies. We demonstrated that HA-19 led to the increase of the protein synthesis by activating mechanistic target of rapamycin complex 1 (mTORC1)/p70 S6K pathways, and also enhanced myoblast proliferation and terminal differentiation via up-regulating of the myogenic transcription factors Pax7, MyoD and Myogenin. The interesting thing was that HA-19 also suppressed protein degradation to prevent myotube atrophy by down-regulating negative growth factors, FoxO1, MuRF1 and Atrogin-1. The results were also supported by puromycin labelling and protein ubiquitination assays. These data revealed that HA-19 possessed a "dual effect" on inhibition of muscle atrophy. In disuse-induced muscle atrophy mice model, HA-19 treatment significantly increased the weights of bilateral tibialis anterior (TA), gastrocnemius (Gastroc.), quadriceps (Quad.), suggesting the effectiveness of HA-19 to remit disuse-induced muscle atrophy. Our finding demonstrated that HA-19 has a great potential as an inhibitor or lead compound for the anti-muscle atrophy drug discovery.

5.
PLoS One ; 14(4): e0214460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30939170

RESUMO

OBJECTIVE: To design and evaluate the accuracy of a novel navigation template suitable for posterior cervical screw placement surgery by using 3D printing technology to improve the existing guiding template design. METHODS: The researchers (including spine surgeons and technicians) used CT to perform thin-slice scanning on 12 cases of normal upper cervical vertebral specimens and defined the screw channels that were completely located in the pedicle without penetrating the cortex as ideal screw channels, then designed the ideal channel of the upper cervical vertebral (atlantoaxial) pedicle screw by computer software which was regarded as the preset values, and recorded the screw entrance point, transverse angle and sagittal angle of the ideal channel. Then, researchers designed the novel navigation templates for placement pedicle screw according to the ideal screw channel preset values and manufactured them with one for every single vertebra by 3D printer. A senior spine surgeon performed the posterior surgery to implant pedicle screw on the specimens by the novel navigation templates, then performed CT thin-slice scanning on the specimens again after removing the screws, and reconstructed the actual screws channel by computer software, recorded the screw entrance point, transverse angle and sagittal angle of the actual channels which were defined as the actual values and evaluated them according to Kawaguchi's pedicle screw evaluation standard finally. The differences between the preoperative preset values of ideal screw channel and the postoperative actual values of actual screw channel were compared by a nonparametric paired rank test. RESULTS: 48 screws were placed on 12 cases of upper cervical vertebral specimens in total. It showed that the grade 0, I, II, III channels in this study were 47, 1, 0, 0, respectively. The grade 0 channels accounted for 97.92% of the total number of channels. There was no significant difference with regard to the screw entrance point, the transverse angle, and the sagittal angle between the preoperative preset values of ideal screw channels and the postoperative actual values of actual screw channels. CONCLUSION: To implant pedicle screw assisted with the novel individually navigation template designed by 3D printed in the posterior cervical surgery can improve accuracy of pedicle screw placement and safety of the surgery.

6.
Eur J Med Chem ; 170: 28-44, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30878830

RESUMO

Pancreatic cancer is one of the most deadly neoplasm with a 5-year survival rate of less than 6% owing to its remarkable tolerance to nutrient starvation, and new drugs and treatment strategies are urgently needed. During a project aiming at discovery of anticancer agents, we performed a structure modification on polycyclic polyprenylated acylphloroglucinols (PPAPs) skeleton, and discovered that PPAP rearranged to a tetrahydroquinolin-2(1H)-one feature. Here, series of tetrahydroquinolin-2(1H)-one derivatives were designed, synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (PANC-1), and the structure-activity relationship was also discussed. Among them, derivative 11k showed the most potent inhibitory activity with an IC50 value of 4.9 µM under nutrient-deprived condition. In contrast, all these derivatives exhibited low cytotoxicity against PANC-1 cells under normal nutrient condition, suggesting that the derivatives appeared to allow alternative tumor cell death mechanisms, and led to less toxicity. Further evaluations demonstrated that 11k decreased colony formation and induced the apoptosis of PANC-1 under nutrient-deprived condition in a concentration dependent manner. In in vivo study, 11k significantly suppressed the tumor development and weight in nude mice. Preliminary mechanism research revealed that 11k clearly downregulated LC3-II expression and increased the level of p62, two key autophagy markers and critical signals for pancreatic tumor growth and progression. Our current findings demonstrated that 11k might be a promising candidate for the new chemotherapeutic molecule of pancreatic cancer, and deserve further study.


Assuntos
Antineoplásicos/química , Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Quinolinas/química , Quinolinas/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos Nus , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Quinolinas/síntese química , Quinolinas/farmacologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-30421857

RESUMO

OBJECTIVES: To evaluate the effect of prior stroke on long-term outcomes in patients undergoing percutaneous coronary interventions (PCI). BACKGROUND: Patients with coronary heart disease (CHD) and prior stroke history have more serious clinical and angiographic conditions, which make the choice of treatment strategy complex. METHODS: A total of 10,724 consecutive patients who underwent PCI from January 2013 to December 2013 were enrolled. 2-Year clinical outcomes between patients with prior stroke (n = 1150) and those with no prior stroke (n =9574) were compared. RESULTS: The proportion of patients with prior stroke was 10.72%. These patients had higher clinical risks (age, sex, and cardiovascular risk factors) and more extensive coronary disease (higher pre-PCI and residual SYNTAX scores). During the 2-year follow-up, patients with prior stroke had a higher incidence of major adverse cardiac and cerebrovascular events (MACCE), all-cause death, stent thrombosis and stroke than those without prior stroke (14.3% vs. 11.8%, p = 0.02; 2.3% vs. 1.1%, p < 0.01; 1.6% vs. 0.8%, p < 0.01; 3.3% vs. 1.1%, p < 0.01, respectively). Multivariable regression analyses identified a positive association between prior stroke and risk of stroke (HR = 2.07, 95%CI: 1.35-3.19, p < 0.01). Propensity score matched analyses (962 pairs) indicated that the only primary end point that differed in incidence between the groups was stroke and prior stroke was the only independent predictor of stroke (HR = 2.31, 95%CI: 1.20-4.45, p = 0.01). CONCLUSIONS: Prior stroke history was the only predictor of risk of post-PCI stroke. The noncerebrovascular adverse events were not increased after adjusted analyses of baseline characteristics and propensity analyses.

8.
Chin Med J (Engl) ; 131(22): 2699-2704, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30425196

RESUMO

Background: The patterns of nonadherence to antiplatelet regimen in stented patients (PARIS) thrombotic risk score are a novel score for predicting the risk of coronary thrombotic events (CTEs) after percutaneous coronary intervention (PCI) with drug-eluting stents. However, the prognostic value of this score has not been fully evaluated in non-Euro-American PCI populations. Methods: We performed a prospective, observational study of 10,724 patients who underwent PCI in Fuwai hospital, China and evaluated the PARIS thrombotic risk score's predictive value of CTEs in the PCI population. The area under the receiver operating characteristic curve (AUROC) was used to assess the predictive value of the PARIS score for CTE. Results: Among 9782 patients without in-hospital events, a total of 95 CTEs occurred during the 2-year follow-up. The PARIS score was significantly higher in patients with CTEs (3.38 ± 2.04) compared with patients without events (2.53 ± 1.70, P < 0.001). According to the risk stratification of the PARIS thrombotic score, the risk of CTEs in the high-risk group was 3.14 times higher than that in the low-risk group (hazard ratio [HR], 3.14; 95% confidence interval [CI], 1.92-5.13; P < 0.001). However, the risk of CTEs in the intermediate-risk and low-risk groups was not significant (HR, 1.39; 95% CI, [0.86-2.24]; P = 0.184). The PARIS score showed prognostic value in evaluating CTEs in the overall population (AUROC, 0.621; 95% CI, 0.561-0.681), the acute coronary syndrome (ACS) population (AUROC, 0.617; 95% CI, 0.534-0.700; P = 0.003), and the non-ACS population (AUROC, 0.647; 95% CI, 0.558-0.736; P = 0.001). Conclusions: In a real-world Chinese population, the PARIS thrombotic risk score shows a modest prognostic value for CTEs in patients after PCI. This score also has a predictive value for CTEs in the ACS and non-ACS subgroup populations.

9.
J Phys Condens Matter ; 30(38): 385602, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30113017

RESUMO

The magnetic properties of 4d and 5d transition-metal insulating compounds with the honeycomb structure are believed to be described by the Heisenberg-Kitaev model, which contains both the isotropic Heisenberg interaction J and anisotropic Kitaev interaction K. In this paper, we study the single-hole propagation of the t-J-K model in various magnetically ordered phases by the self-consistent Born approximation. We find that there are low-energy coherent quasiparticle (QP) excitations in all of these phases which appear firstly around the K point in the first Brillouin zone (BZ), but the bandwidths of these QPs are very small due to the hole-magnon coupling. Interestingly, in the zigzag phase relevant to recent experiments, though the QP weights are largely suppressed in the physical spectra in the first BZ, we find that they recover in the extended BZs. Moreover, our results reveal that the low-energy QP spectra are reduced with the increase of K.

10.
Nat Commun ; 9(1): 2591, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29968725

RESUMO

Topological magnons are emergent quantum spin excitations featured by magnon bands crossing linearly at the points dubbed nodes, analogous to fermions in topological electronic systems. Experimental realisation of topological magnons in three dimensions has not been reported so far. Here, by measuring spin excitations (magnons) of a three-dimensional antiferromagnet Cu3TeO6 with inelastic neutron scattering, we provide direct spectroscopic evidence for the coexistence of symmetry-protected Dirac and triply degenerate nodes, the latter involving three-component magnons beyond the Dirac-Weyl framework. Our theoretical calculations show that the observed topological magnon band structure can be well described by the linear-spin-wave theory based on a Hamiltonian dominated by the nearest-neighbour exchange interaction J1. As such, we showcase Cu3TeO6 as an example system where Dirac and triply degenerate magnonic nodal excitations coexist, demonstrate an exotic topological state of matter, and provide a fresh ground to explore the topological properties in quantum materials.

11.
Front Pharmacol ; 9: 631, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29962949

RESUMO

Background: Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain and abnormalities in defecation associated with psychiatric disorders such as depression and anxiety due to the dysfunction of brain-gut axis. This study aims to determine whether trans-Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction. Methods: ICR male mice were exposed to the CACS for 3 weeks. trans-Resveratrol were administrated daily (2.5, 5, and 10 mg/kg, i.g.) 30 min before CACS. Behavioral tests were performed to evaluate the treatment effects of trans-Resveratrol on IBS. Hippocampus tissues were collected and processed Golgi staining and immuno-blot analysis. Ileum and colon tissues were collected and processed Hematoxylin and Eosin staining and immuno-blot analysis. Results: Administration with trans-Resveratrol before CACS for 3 weeks significantly reversed CACS-induced depression- and anxiety-like behaviors and intestinal dysfunction in mice, which implied a crucial role of trans-Resveratrol in treatment of IBS-like disorder. Furthermore, trans-Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that trans-Resveratrol normalized phosphodiesterases 4A (PDE4A) expression and CREB-BDNF signaling that were disturbed by CACS. The increased pCREB and BDNF expression in the hippocampus were found, while decreased pCREB and BDNF levels were observed after treatment with trans-Resveratrol. Conclusions: The dual effects of trans-Resveratrol on stress-induced psychiatric and intestinal dysfunction may be related to normalization of PDE4A expression and subsequent pCREB-BDNF signaling in the hippocampus, ileum and colon.

12.
Chin Med J (Engl) ; 131(12): 1390-1396, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29893355

RESUMO

Background: Residual SYNTAX score (rSS) and its derived indexes including SYNTAX revascularization index (SRI) and clinical rSS had been developed to quantify and describe the extent of incomplete revascularization. This study was conducted to explore the utility of the three scores among real-world patients after percutaneous coronary intervention (PCI). Methods: From January 2013 to December 2013, patients underwent PCI treatment at Fuwai Hospital were included. The primary endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events. The secondary endpoints were myocardial infarction, revascularization, stroke, and stent thrombosis. Kaplan-Meier methodology was used to determine the outcomes. Cox multivariable regression was to test the associations between scores and all-cause mortality. Results: A total of 10,344 patients were finally analyzed in this study. Kaplan-Meier survival analysis indicated that greater residual coronary lesions quantified by rSS and its derived indexes were associated with increased risk of adverse cardiovascular events. However, after multivariate analysis, only clinical rSS was an independent predictor of 2-year all-cause death (hazard ratio: 1.02, 95% confidence interval: 1.01-1.03, P < 0.01). By receiver operating characteristic (ROC) curve analysis, clinical rSS had superior predictability of 2-year all-cause death than rSS and SRI (area under ROC curve [AUC]: 0.59 vs. 0.56 vs. 0.56, all P < 0.01), whereas rSS was superior in predicting repeat revascularization than clinical rSS and SRI (AUC: 0.62 vs. 0.61 vs. 0.61; all P < 0.01). When comparing the predictive capability of rSS ≥8 with SRI <70%, their predictabilities were not significantly different. Conclusions: This study indicates that all three indexes (rSS, clinical rSS, and SRI) are able to risk-stratify patients and predict 2-year outcomes after PCI. However, their prognostic capabilities are different.


Assuntos
Intervenção Coronária Percutânea/métodos , Idoso , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Modelos de Riscos Proporcionais , Medição de Risco , Resultado do Tratamento
13.
Chin Med J (Engl) ; 131(12): 1406-1411, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29595186

RESUMO

Background: The Patterns of Non-Adherence to Anti-Platelet Regimens in Stented Patients (PARIS) bleeding score is a novel score for predicting the out-of-hospital bleeding risk after percutaneous coronary intervention (PCI). However, whether this score has the same value in non-European and American populations is unclear. This study aimed to assess the PARIS bleeding score's predictive value of bleeding in patients after PCI in the Chinese population. Methods: We performed a prospective, observational study of 10,724 patients who underwent PCI from January to December 2013, in Fuwai Hospital, China. We defined the primary end point as major bleeding (MB) according to Bleeding Academic Research Consortium definition criteria including Type 2, 3, or 5. The predictive value of the PARIS bleeding score was assessed with the area under the receiver operating characteristic (AUROC) curve. Results: Of 9782 patients, 245 (2.50%) MB events occurred during the 2 years of follow-up. The PARIS bleeding score was significantly higher in the MB group than that of non-MB group (4.00 [3.00, 5.00] vs. 3.00 [2.00, 5.00], Z = 3.71, P < 0.001). According to risk stratification of the PARIS bleeding score, the bleeding risk in the intermediate- and high-risk groups was 1.50 times (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.160-1.950; P = 0.002) and 2.27 times higher (HR: 2.27; 95% CI: 1.320-3.900; P = 0.003) than that in the low-risk group. The PARIS bleeding score showed a moderate predictive value for MB in the overall population (AUROC: 0.568, 95% CI: 0.532-0.605; P < 0.001) and acute coronary syndrome (ACS) subgroup (AUROC: 0.578, 95% CI: 0.530-0.626; P = 0.001) and tended to be predictive in the non-ACS subgroup (AUROC: 0.556, 95% CI: 0.501-0.611; P = 0.054). Conclusion: The PARIS bleeding score shows good clinical value for risk stratification and has a significant, but relatively limited, prognostic value for out-of-hospital bleeding in the Chinese population after PCI.


Assuntos
Hemorragia/diagnóstico , Intervenção Coronária Percutânea/métodos , Síndrome Coronariana Aguda/patologia , Síndrome Coronariana Aguda/cirurgia , Idoso , Plaquetas/fisiologia , China , Feminino , Hemorragia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
14.
Phys Rev Lett ; 120(8): 087201, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29543015

RESUMO

We report on comprehensive results identifying the ground state of a triangular-lattice structured YbZnGaO_{4} as a spin glass, including no long-range magnetic order, prominent broad excitation continua, and the absence of magnetic thermal conductivity. More crucially, from the ultralow-temperature ac susceptibility measurements, we unambiguously observe frequency-dependent peaks around 0.1 K, indicating the spin-glass ground state. We suggest this conclusion holds also for its sister compound YbMgGaO_{4}, which is confirmed by the observation of spin freezing at low temperatures. We consider disorder and frustration to be the main driving force for the spin-glass phase.

15.
Chin Med J (Engl) ; 131(3): 262-267, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29363639

RESUMO

BACKGROUND: There is scanty evidence concerning the ability of Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) and Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (ACUITY-HORIZONS) scores to predict out-of-hospital bleeding risk after percutaneous coronary interventions (PCIs) with drug-eluting stents (DES) in patients receiving dual antiplatelet therapy. We aimed to assess and compare the long-term prognostic value of these scores regarding out-of-hospital bleeding risk in such patients. METHODS: We performed a prospective observational study of 10,724 patients undergoing PCI between January and December 2013 in Fuwai Hospital, China. All patients were followed up for 2 years and evaluated through the Fuwai Hospital Follow-up Center. Major bleeding was defined as Types 2, 3, and 5 according to Bleeding Academic Research Consortium Definition criteria. RESULTS: During a 2-year follow-up, 245 of 9782 patients (2.5%) had major bleeding (MB). CRUSADE (21.00 [12.00, 29.75] vs. 18.00 [11.00, 26.00], P < 0.001) and ACUITY-HORIZONS (9.00 [3.00, 14.00] vs. 6.00 [3.00, 12.00], P < 0.001) risk scores were both significantly higher in the MB than non-MB groups. Both scores showed a moderate predictive value for MB in the whole study cohort (area under the receiver-operating characteristics curve [AUROC], 0.565; 95% confidence interval [CI], 0.529-0.601, P = 0.001; AUROC, 0.566; 95% CI, 0.529-0.603, P < 0.001, respectively) and in the acute coronary syndrome (ACS) subgroup (AUROC: 0.579, 95% CI: 0.531-0.627, P = 0.001; AUROC, 0.591; 95% CI, 0.544-0.638, P < 0.001, respectively). However, neither score was a significant predictor in the non-ACS subgroup (P > 0.05). The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup. CONCLUSIONS: CRUSADE and ACUITY-HORIZONS scores showed statistically significant but relatively limited long-term prognostic value for out-of-hospital MB after PCI with DES in a cohort of Chinese patients. The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup.

16.
Acta Pharmacol Sin ; 39(2): 230-242, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28816232

RESUMO

Osteoporotic treatments have largely depended on antiresorptive or anabolic drugs; but the former also suppresses new bone formation, and the latter only includes human parathyroid hormone. There is no drug that has a dual effect to inhibit bone resorption and to stimulate bone formation simultaneously. Here, we report a small molecule, a quinoxaline derivative of oleanolic acid (QOA-8a) that plays such dual roles in osteoblasts and osteoclasts in the treatment of osteoporosis. Osteoclast differentiation was induced by incubation of primary mouse bone marrow-derived macrophages in the presence of RANKL and M-CSF, treatment with QOA-8a dose-dependently inhibited the osteoclast formation with an IC50 value of 0.098 µmol/L. QOA-8a also directly acted on osteoblasts, and stimulated new bone formation in murine calvarial bones in vitro and in vivo. In an OVX rat model, administration of QOA-8a (1, 5 mg·kg-1·d-1, po) for 16 weeks effectively prevented OVX-induced bone loss, accompanied by decreased serum levels of the bone resorption marker CTX-1 and increased serum levels of osteoblast marker N-MID-OT. Meaningfully, our preliminary study revealed that QOA-8a down-regulated the ERK1/2 signal in osteoclasts and up-regulated the signal in osteoblasts. QOA-8a showed dual functions in both animal and human osteoclastogenesis and osteoblastogenesis. Our results demonstrate that QOA-8a might serve as a lead compound with a dual function of bone anabolic and anti-resorptive effects in the development of anti-osteoporosis agents.


Assuntos
Reabsorção Óssea/prevenção & controle , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/uso terapêutico , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Quinoxalinas/uso terapêutico , Animais , Feminino , Humanos , Fator Estimulador de Colônias de Macrófagos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Substâncias Protetoras/uso terapêutico , Ligante RANK/farmacologia , Células RAW 264.7 , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
17.
Biomed Environ Sci ; 31(12): 859-866, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30636655

RESUMO

OBJECTIVE: The predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable coronary artery disease (SCAD) in the drug-eluting stent era is not yet clear. We aimed to evaluate the prognostic value of NT-proBNP in SCAD patients after percutaneous coronary intervention (PCI). METHODS: We examined 4,293 consecutive SCAD patients who underwent PCI between January 2013 and December 2013 in Fuwai Hospital, China. The primary endpoint was all-cause death. NT-proBNP levels were measured before PCI using Elisa kits (Biomedica, Austria). The indication for PCI was based on the degree of coronary stenosis and evidence of ischemia. RESULTS: Among 3,187 SCAD patients with NT-proBNP data, after a 2-year follow-up, NT-proBNP levels were predictive for all-cause death in the SCAD population [area under the receiver operating characteristic curve, 0.768; 95% confidence interval (CI), 0.687-0.849; P < 0.001]. At the optimum cutoff point of 732 pg/mL, the sensitivity and specificity of death was 75.0% and 72.3%, respectively. In a multivariable Cox regression model, the death hazard ratio was 6.43 (95% CI, 2.99-13.82; P < 0.001) for patients with NT-proBNP levels ⪖ 732 pg/mL, compared with < 732 pg/mL. CONCLUSION: NT-proBNP is a strong predictor of 2-year death with SCAD after PCI in the drug-eluting stent era.


Assuntos
Doença da Artéria Coronariana/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Intervenção Coronária Percutânea , Idoso , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Doença da Artéria Coronariana/mortalidade , Stents Farmacológicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC
18.
Thromb Res ; 159: 5-12, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28942357

RESUMO

INTRODUCTION: Stent thrombosis (ST) is a rare but catastrophic complication of percutaneous coronary intervention, leading to poor prognosis. Endothelin-1 (ET-1) plays an important role in endothelial dysfunction and thrombogenesis. However, the impact of big ET-1 level on ST in patients with coronary stenting is unknown. We aimed to evaluate big ET-1 level as a potential predictor of ST in patients undergoing percutaneous coronary intervention. MATERIALS AND METHODS: From January 2013 to December 2013, 8106 consecutive patients underwent successful coronary stent implantation and were prospectively enrolled in this study. Patients were stratified into three groups based on plasma big ET-1 level at admission. RESULTS: The incidence of definite and probable ST at 2years postoperatively was 0.84%; ST incidence was lowest in the low big ET-1 group (0.56%), highest in the high big ET-1 group (1.48%), and intermediate in the medium big ET-1 group (0.74%, log-rank p=0.001). Compared with the low big ET-1 group, the multivariate-adjusted hazard ratio (HR) for ST in the high big ET-1 group was 2.06 (95% confidence interval (CI) 1.14-3.73, p=0.017). In subgroup analyses, high big ET-1 level was independently associated with ST in patients with acute coronary syndrome (HR 2.29, 95% CI 1.03-5.06, p=0.041), but not in those with stable coronary artery disease (p=0.331), and tended to be associated with older age. CONCLUSIONS: Plasma big ET-1 level is a valuable independent predictor of ST in patients with coronary stents, especially in the acute coronary syndrome population.


Assuntos
Trombose Coronária/sangue , Trombose Coronária/etiologia , Endotelina-1/sangue , Intervenção Coronária Percutânea/efeitos adversos , Stents/efeitos adversos , China , Trombose Coronária/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
19.
J Cancer ; 8(10): 1786-1794, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28819375

RESUMO

Lymphangiogenesis plays an important role in cancer metastasis. Bone marrow-derived mesenchymal stem cells (BMMSCs) migrate to the site of tumorigenesis and in turn promote the metastasis. However, whether BMMSCs involve in the lymphangiogenesis of lung cancer is unclear. Jinfukang has clinically been used for the treatment of non small cell lung cancer (NSCLC) in China. In this study, to investigate the involvement of BMMSCs in lymphangiogenesis in lung cancer, and evaluate the inhibitory effect of Jinfukang on the lymphangiogenesis, chimeric mice were prepared by transplanting bone marrow from green fluorescent protein (GFP) transgenic mice (C57BL/6-EGFP) into irradiated C57BL/6 mice. Then, the chimeric mice were injected subcutaneously with freshly prepared Lewis lung carcinoma cell suspension to make lung tumor model, and the model mice were further orally administrated with Jinfukang once per day for 3 weeks. Four weeks after the bone marrow transplantation, GFP-positive cells primarily existed in bone marrow of acceptor mice, and three more weeks after, Lewis lung carcinoma cells formed a tumor mass in chimeric mice. Observation of GFP-positive cells revealed that BMMSCs transferred into the lung tumor. Immunofluorescent analyses of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), a lymphatic endothelium marker, demonstrated a part of lymphatic endothelial cells in lung cancer were derived from BMMSCs, and those lymphatic endothelial cells contributed to the lung tumor lymphangiogenesis. Furthermore, Jinfukang treatment resulted in a significant reduction of the average weight of the tumor mass in chimeric mice, and displayed a significant lower number of LYVE-1 positive cells. The present results suggest that BMMSCs transfer to tumor, differentiate into lymphatic endothelial cells, and involve in the lymphangiogenesis in lung cancer of mice. Jinfukang inhibits the lung tumor mass via suppression of the BMMSCs transformation and lung tumor lymphangiogenesis. Our findings might provide the potential for the cancer therapies.

20.
Perfusion ; 32(8): 670-674, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28699424

RESUMO

OBJECTIVE: To present our experience of the endovascular treatment of subclavian artery aneurysms (SAAs) and analyze the clinical manifestations, imaging findings and treatment outcomes. METHODS: In this retrospective study, nine patients with SAAs underwent endovascular stent placement in our center between July 2011 and June 2016. Clinical features, imaging findings, treatment outcomes and follow-up results of these SAA patients were retrospectively analyzed. RESULTS: Nine patients were diagnosed with SAAs by computer tomography angiography (CTA). Five patients underwent percutaneous endovascular stent placement in the subclavian artery. Three patients underwent endovascular repair of the SAAs with coil embolization and stent graft. One patient underwent stent graft implantation by the simultaneous kissing stent technique. Five patients had their symptoms relieved and thrombosis occurred in one case. The mean follow-up period was 17 months, ranging from 8 to 40 months. CONCLUSION: For patients with SAAs, endovascular treatment is a feasible choice, with a high success rate, few complications and good clinical outcomes.


Assuntos
Aneurisma/terapia , Procedimentos Endovasculares/métodos , Artéria Subclávia/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA