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1.
Bioinformatics ; 39(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36571479

RESUMO

MOTIVATION: Precise reconstruction of neuronal arbors is important for circuitry mapping. Many auto-tracing algorithms have been developed toward full reconstruction. However, it is still challenging to trace the weak signals of neurite fibers that often correspond to axons. RESULTS: We proposed a method, named the NeuMiner, for tracing weak fibers by combining two strategies: an online sample mining strategy and a modified gamma transformation. NeuMiner improved the recall of weak signals (voxel values <20) by a large margin, from 5.1 to 27.8%. This is prominent for axons, which increased by 6.4 times, compared to 2.0 times for dendrites. Both strategies were shown to be beneficial for weak fiber recognition, and they reduced the average axonal spatial distances to gold standards by 46 and 13%, respectively. The improvement was observed on two prevalent automatic tracing algorithms and can be applied to any other tracers and image types. AVAILABILITY AND IMPLEMENTATION: Source codes of NeuMiner are freely available on GitHub (https://github.com/crazylyf/neuronet/tree/semantic_fnm). Image visualization, preprocessing and tracing are conducted on the Vaa3D platform, which is accessible at the Vaa3D GitHub repository (https://github.com/Vaa3D). All training and testing images are cropped from high-resolution fMOST mouse brains downloaded from the Brain Image Library (https://www.brainimagelibrary.org/), and the corresponding gold standards are available at https://doi.brainimagelibrary.org/doi/10.35077/g.25. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Software , Animais , Camundongos , Neurônios , Neuritos , Encéfalo
2.
Bioorg Chem ; 150: 107550, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38878756

RESUMO

Cyclin-dependent kinase 9 (CDK9) plays a role in transcriptional regulation, which had become an attractive target for discovery of antitumor agent. In this work, beyond traditional CDK9 inhibitor with bidentate ligands in ATP binding domain, a series of novel CDK9 inhibitor with tridentate ligand were designed and synthesized. Surprisingly, this unique tridentate ligand structure endows better CDK9 inhibition selectivity compared to other CDK subtypes, and the lead candidate compound Z4-7a showed effective proliferation inhibition in HCT116 cells with acceptable pharmacokinetic properties. Research on the mechanism indicated that Z4-7a could induce apoptosis in the HCT116 cell line by inhibiting phosphorylation of RNA polymerase II at Ser2, which resulted in the inhibition of apoptosis-related genes and proteins expression. In brief, introduction of tridentate ligand might work as a promising strategy for the development of novel selective CDK9 inhibitor.

3.
Int J Mol Sci ; 25(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38396931

RESUMO

A series of novel echinatin derivatives with 1,3,4-oxadiazole moieties were designed and synthesized. Most of the newly synthesized compounds exhibited moderate antiproliferative activity against the four cancer cell lines. Notably, Compound T4 demonstrated the most potent activity, with IC50 values ranging from 1.71 µM to 8.60 µM against the four cancer cell lines. Cell colony formation and wound healing assays demonstrated that T4 significantly inhibited cell proliferation and inhibited migration. We discovered that T4 exhibited moderate binding affinity with the c-KIT protein through reverse docking. The results were effectively validated through subsequent molecular docking and c-KIT enzyme activity assays. In addition, Western blot analysis revealed that T4 inhibits the phosphorylation of downstream proteins of c-KIT. The results provide valuable inspiration for exploring novel insights into the design of echinatin-related hybrids as well as their potential application as c-KIT inhibitors to enhance the efficacy of candidates.


Assuntos
Antineoplásicos , Chalconas , Neoplasias , Oxidiazóis , Humanos , Relação Estrutura-Atividade , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Proliferação de Células , Estrutura Molecular , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga
4.
Brief Bioinform ; 22(6)2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33940596

RESUMO

The poly (ADP-ribose) polymerase-1 (PARP1) has been regarded as a vital target in recent years and PARP1 inhibitors can be used for ovarian and breast cancer therapies. However, it has been realized that most of PARP1 inhibitors have disadvantages of low solubility and permeability. Therefore, by discovering more molecules with novel frameworks, it would have greater opportunities to apply it into broader clinical fields and have a more profound significance. In the present study, multiple virtual screening (VS) methods had been employed to evaluate the screening efficiency of ligand-based, structure-based and data fusion methods on PARP1 target. The VS methods include 2D similarity screening, structure-activity relationship (SAR) models, docking and complex-based pharmacophore screening. Moreover, the sum rank, sum score and reciprocal rank were also adopted for data fusion methods. The evaluation results show that the similarity searching based on Torsion fingerprint, six SAR models, Glide docking and pharmacophore screening using Phase have excellent screening performance. The best data fusion method is the reciprocal rank, but the sum score also performs well in framework enrichment. In general, the ligand-based VS methods show better performance on PARP1 inhibitor screening. These findings confirmed that adding ligand-based methods to the early screening stage will greatly improve the screening efficiency, and be able to enrich more highly active PARP1 inhibitors with diverse structures.


Assuntos
Bases de Dados de Compostos Químicos , Simulação de Acoplamento Molecular , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/química , Avaliação Pré-Clínica de Medicamentos , Humanos , Poli(ADP-Ribose) Polimerase-1/química , Relação Estrutura-Atividade
5.
Catheter Cardiovasc Interv ; 101(6): 980-994, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37002950

RESUMO

BACKGROUND: COVID-19 has disrupted the care of all patients, and little is known about its impact on the utilization and short-term mortality of percutaneous coronary intervention (PCI) patients, particularly nonemergency patients. METHODS: New York State's PCI registry was used to study the utilization of PCI and the presence of COVID-19 in four patient subgroups ranging in severity from ST-elevation myocardial infarction (STEMI) to elective patients before (December 01, 2018-February 29, 2020) and during the COVID-19 era (March 01, 2020-May 31, 2021), as well as to examine the impact of different COVID severity levels on the mortality of different types of PCI patients. RESULTS: Decreases in the mean quarterly PCI volume from the prepandemic period to the first quarter of the pandemic ranged from 20% for STEMI patients to 61% for elective patients, with the other two subgroups having decreases in between these values. PCI quarterly volume rebounds from the prepandemic period to the second quarter of 2021 were in excess of 90% for all patient subgroups, and 99.7% for elective patients. Existing COVID-19 was rare among PCI patients, ranging from 1.74% for STEMI patients to 3.66% for elective patients. PCI patients with COVID-19 and acute respiratory distress syndrome (ARDS) who were not intubated, and PCI patients with COVID-19 and ARDS who were either intubated or were not intubated because of Do Not Resuscitate//Do Not Intubate status had higher risk-adjusted mortality ([adjusted ORs = 10.81 [4.39, 26.63] and 24.53 [12.06, 49.88], respectively]) than patients who never had COVID-19. CONCLUSIONS: There were large decreases in the utilization of PCI during COVID-19, with the percentage of decrease being highly sensitive to patient acuity. By the second quarter of 2021, prepandemic volumes were nearly restored for all patient subgroups. Very few PCI patients had current COVID-19 throughout the pandemic period, but the number of PCI patients with a COVID-19 history increased steadily during the pandemic. PCI patients with COVID-19 accompanied by ARDS were at much higher risk of short-term mortality than patients who never had COVID-19. COVID-19 without ARDS and history of COVID-19 were not associated with higher mortality for PCI patients as of the second quarter of 2021.


Assuntos
COVID-19 , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , New York/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento
6.
Bioorg Chem ; 139: 106752, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37499529

RESUMO

A series of novel ziyuglycoside II derivatives were synthesized based on the classical 1,2,3-triazole moiety. Among the tested derivatives (Z-1 - Z-15), the compound Z-15 demonstrated the most potent antiproliferative effect on K562, MCF-7 and MV411 cell lines. Moreover, Z-15 did not show obvious cytotoxicity on MCF-10A cell, a human normal mammary epithelial cell. The cell colony formation assay showed that, compared to ziyuglycoside II and 5-fluorouracil, Z-15 could inhibit cell proliferation more robustly. Wound healing assays indicated that Z-15 could significantly inhibit MCF-7 cell migration. Further mechanistic research revealed that Z-15 induced mitochondrial-mediated apoptosis and autophagy in MCF-7 cell line in a dose-dependent manner.

7.
Skin Res Technol ; 29(12): e13539, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38115632

RESUMO

BACKGROUND: Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure. MATERIALS AND METHODS: The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio. RESULTS: SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness. CONCLUSION: Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.


Assuntos
Antioxidantes , Células HaCaT , Humanos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/química , Estresse Oxidativo , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Raios Ultravioleta/efeitos adversos , Queratinócitos/metabolismo
8.
Sensors (Basel) ; 23(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36679646

RESUMO

Some recent studies use a convolutional neural network (CNN) or long short-term memory (LSTM) to extract gait features, but the methods based on the CNN and LSTM have a high loss rate of time-series and spatial information, respectively. Since gait has obvious time-series characteristics, while CNN only collects waveform characteristics, and only uses CNN for gait recognition, this leads to a certain lack of time-series characteristics. LSTM can collect time-series characteristics, but LSTM results in performance degradation when processing long sequences. However, using CNN can compress the length of feature vectors. In this paper, a sequential convolution LSTM network for gait recognition using multimodal wearable inertial sensors is proposed, which is called SConvLSTM. Based on 1D-CNN and a bidirectional LSTM network, the method can automatically extract features from the raw acceleration and gyroscope signals without a manual feature design. 1D-CNN is first used to extract the high-dimensional features of the inertial sensor signals. While retaining the time-series features of the data, the dimension of the features is expanded, and the length of the feature vectors is compressed. Then, the bidirectional LSTM network is used to extract the time-series features of the data. The proposed method uses fixed-length data frames as the input and does not require gait cycle detection, which avoids the impact of cycle detection errors on the recognition accuracy. We performed experiments on three public benchmark datasets: UCI-HAR, HuGaDB, and WISDM. The results show that SConvLSTM performs better than most of those reporting the best performance methods, at present, on the three datasets.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Marcha , Aceleração , Memória de Longo Prazo
9.
Inorg Chem ; 61(37): 14864-14870, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36074725

RESUMO

A bimetallic MOF, CoNi(EIM)2(DCA)2 (1), containing an energetic 1-ethylimidazole (EIM) ligand and a hypergolic linker, dicyandiamide (DCA), was synthesized via a facile method. A fascinating three-dimensional reticular architecture was observed by single-crystal X-ray diffraction in this bimetallic MOF, whereas the corresponding monometallic compounds Co(EIM)4(DCA)2 (2) and Ni(EIM)4(DCA)2 (3) were in the mononuclear coordination mode. Uniformly distributed Co and Ni were observed in the bimetallic MOF crystals by SEM-EDS elemental mapping. Bimetallic MOF 1 was thermally stable and insensitive to mechanical stimuli and possessed an excellent energetic density (22.37 kJ·g-1). Using 1 as a hypergolic promoter, the ignition delay time of 1-butyl-3-methylimidazolium dicyanamide (BMIM DCA) was reduced from 53 to 37 ms, better than that of 2 and 3 as promoters, due to the synergistic catalysis of the bimetal. Furthermore, the thermal decomposition mechanisms of BMIM DCA with 1, 2, and 3 were studied by differential scanning calorimetry (DSC). 1 had the best catalytic performance in BMIM DCA thermolysis with a decrease in the decomposition temperature from 314.5 to 308.0 °C and a decrease in the activation energy by 16.3%. All results shed light on the better catalytic effect of the bimetallic MOF on ionic liquid hypergolic ignition than monometallic coordination compounds.

10.
Sensors (Basel) ; 22(13)2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35808530

RESUMO

As an advanced technology, simultaneous wireless information and power transfer (SWIPT), combined with the internet of things (IoT) devices, can effectively extend the online cycle of the terminal. To cope with the fluctuation of energy harvesting by the hybrid access points (H-AP), the energy cooperation base station is introduced to realize the sharing of renewable energy. In this paper, we study the SWIPT-enabled IoT networks with cooperation. Our goal is to maximize the energy efficiency of the system, and at the same time, we need to meet the energy harvesting constraints, user quality of service (QoS) constraints and transmission power constraints. We jointly solve the power allocation, time switching and energy cooperation problems. Because this problem is a nonlinear programming problem, it is difficult to solve directly, so we use the alternating variable method, the iterative algorithm is used to solve the power allocation and time switching problem, and the matching algorithm is used to solve the energy cooperation problem. Simulation results show that the proposed algorithm has obvious advantages in energy efficiency performance compared with the comparison algorithm. At the same time, it is also proved that the introduction of energy cooperation technology can effectively reduce system energy consumption and improve system energy efficiency.

11.
Int J Mol Sci ; 23(24)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36555409

RESUMO

A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC50 values ranging from 4.07 µM to 9.71 µM against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism studies reveal that A8 induces apoptosis and ferroptosis in MCF-7 cells in a dose-dependent manner, and CYPs inhibition assays reveal that A8 has a moderate inhibitory effect on CYP1A2 and CYP3A4 in the human body at 10 µM. The present work indicates that hybrid A8 may merit further investigation as a potential therapeutic agent.


Assuntos
Antineoplásicos , Artemisininas , Ferroptose , Humanos , Células MCF-7 , Estrutura Molecular , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Apoptose , Artemisininas/farmacologia , Proliferação de Células , Relação Estrutura-Atividade , Linhagem Celular Tumoral
12.
Inorg Chem ; 60(7): 5100-5106, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760591

RESUMO

In this study, a hypergolic linker (dicyanamide, DCA) and a high-energy nitrogen-rich ligand (1,5-diaminotetrazole, DAT) were applied to construct high-energy metal-organic frameworks (HEMOFs) with hypergolic property. Three novel metal-organic frameworks (MOFs) were synthesized via a mild method with fascinating 2D polymeric architectures, and they could ignite spontaneously upon contact with white fuming nitric acid (WFNA). The gravimetric energy densities of the three HEMOFs all exceeded 26.2 kJ·g-1. The cupric MOF exhibits the highest gravimetric and volumetric energy density of 27.5 kJ·g-1 and 51.3 kJ·cm-3, respectively. By adjusting the metal cations, high-energy ligands and hypergolic linkers can improve the performance of hypergolic MOFs. This work provides a strategy for manufacturing MOFs as potential high-energy hypergolic fuels.

13.
Int J Mol Sci ; 22(24)2021 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-34948406

RESUMO

Based on the strategy of the "tail approach", 15 novel saccharide-modified sulfonamides were designed and synthesised. The novel compounds were evaluated as inhibitors of three human carbonic anhydrase (CA) isoforms, namely cytoplasmic CA II, transmembrane CA IX, and XII. Most of these compounds showed good activity against CAs and high topological polar surface area (TPSA) values, which had a positive effect on the selective inhibition of transmembrane isoforms CA IX and XII. In the in vitro activity studies, compounds 16a, 16b, and 16e reduced the viability of HT-29 and MDA-MB-231 cells with a high expression of CA IX under hypoxia. The inhibitory activity of compound 16e on the human osteosarcoma cell line MG-63 with a high expression of CA IX and XII was better than that of AZM. Moreover, high concentrations of compounds 16a and 16b reversed the acidification of the tumour microenvironment. In addition, compound 16a had a certain inhibitory effect on the migration of MDA-MB-231 cells. All the above results indicate that the saccharide-modified sulfonamide has further research value for the development of CA IX inhibitors.


Assuntos
Anidrase Carbônica IX/antagonistas & inibidores , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Sulfonamidas/química , Sulfonamidas/farmacologia , Antígenos de Neoplasias/metabolismo , Anidrase Carbônica IX/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Linhagem Celular Tumoral , Células HT29 , Humanos , Simulação de Acoplamento Molecular , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Sulfonamidas/síntese química
14.
Int J Mol Sci ; 22(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067452

RESUMO

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the "tail approach" and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.


Assuntos
Carboidratos/farmacologia , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Tiadiazóis/síntese química , Tiadiazóis/farmacologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células HT29 , Humanos , Simulação de Acoplamento Molecular , Microambiente Tumoral/efeitos dos fármacos
15.
Catheter Cardiovasc Interv ; 96(4): 731-740, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31642597

RESUMO

BACKGROUND: Target lesion percutaneous coronary intervention (TLPCI) within 1 year of PCI has been proposed by critics of public reporting of short-term mortality as an alternative measure for PCI reporting. METHODS: New York's PCI registry was used to identify 1-year repeat TLPCI and 1-year repeat TLPCI/mortality for patients discharged between December 1, 2013 and November 30, 2014. Significant independent predictors of the outcomes were identified. Hospital and cardiologist risk-adjusted outcomes were calculated, and outlier status and correlations of risk-adjusted rates were examined for the three outcomes. RESULTS: The adverse outcome rates were 1.30, 4.21, and 8.97% for in-hospital/30-day mortality, 1-year repeat TLPCI, and 1-year repeat TLPCI/mortality. There were many commonalities but also many differences in significant predictors of the outcomes. Hospital and cardiologist risk-adjusted 1-year repeat TLPCI rates and repeat TLPCI/mortality rates were poorly correlated with risk-adjusted in-hospital/30-day mortality rates (eg, Spearman R = -.16 [p = .23] and .27 [p = .04], respectively, for hospital 1-year repeat TLPCI vs. in-hospital/30-day mortality). Many more providers were found to have significantly higher and lower rates for repeat TLPCI than for short-term mortality. CONCLUSIONS: Hospital and cardiologist quality assessments are very different for TLPCI and repeat TLPCI/mortality than they are for short-term mortality. Repeat TLPCI/mortality rates are highly correlated with repeat TLPCI rates, but outlier providers differ. More study of repeat TLPCI and all the patient, cardiologist, and hospital factors associated with it may be required before using it as a supplement to, or in lieu of, short-term mortality in public reporting of PCI outcomes.


Assuntos
Doença da Artéria Coronariana/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde/normas , Intervenção Coronária Percutânea/normas , Registros Públicos de Dados de Cuidados de Saúde , Garantia da Qualidade dos Cuidados de Saúde/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Idoso , Idoso de 80 Anos ou mais , Cardiologistas/normas , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Hospitais/normas , Humanos , Masculino , Pessoa de Meia-Idade , New York , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Sistema de Registros , Retratamento/normas , Fatores de Tempo , Resultado do Tratamento
16.
Biochem Biophys Res Commun ; 517(3): 407-412, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31376931

RESUMO

Periprosthetic asepteic loosening, caused by wear debris, is one of the most severe complications, generally resulting in implant failure. Extensive osteoclast formation and activation are considered as the cause for periprosthetic osteolysis. However, few approaches have been approved to be used for preventing early-stage periprosthetic osteolysis. In this study, we investigated the preventive effects of CEP on titanium particles-induced osteolysis in a murine calvaria model. This inhibitory effect was confirmed to be realized by attenuating osteoclastogenesis in vivo. In addition, CEP markedly reduced wear particles-induced elevation of receptor activator of nuclear factor kappa B ligand (RANKL)/Osteoprotegerin (OPG) ratio in vivo. In conclusion, these data concluded that CEP demonstrated a preventive effect of CEP on titanium particles induced osteolysis, suggesting that CEP might be a novel therapeutic for periprosthesis loosening.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Benzilisoquinolinas/farmacologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteólise/prevenção & controle , Osteoprotegerina/genética , Ligante RANK/genética , Titânio/efeitos adversos , Animais , Prótese Ancorada no Osso , Interface Osso-Implante/cirurgia , Catepsina D/genética , Catepsina D/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Masculino , Camundongos , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese/genética , Osteólise/induzido quimicamente , Osteólise/genética , Osteólise/patologia , Osteoprotegerina/antagonistas & inibidores , Osteoprotegerina/metabolismo , Falha de Prótese/efeitos dos fármacos , Ligante RANK/antagonistas & inibidores , Ligante RANK/metabolismo , Crânio/efeitos dos fármacos , Crânio/cirurgia , Fosfatase Ácida Resistente a Tartarato/genética , Fosfatase Ácida Resistente a Tartarato/metabolismo
17.
BMC Infect Dis ; 19(1): 1082, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881849

RESUMO

BACKGROUND: To investigate the clinical features of septic pulmonary embolism (SPE) cases and prognostic factors for in-hospital mortality in China. METHODS: A retrospective analysis was conducted of SPE patients hospitalized between January 2007 and June 2018 in the Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University. RESULTS: A total of 98 patients with SPE were identified. All patients had bilateral multiple peripheral nodules on chest computed tomography. The most common pathogen found in blood culture was Staphylococcus aureus (10/33, 30.3%). Transthoracic echocardiography was performed in 39 patients and 20 showed vegetations. Bronchoscopy was performed in 24 patients. Bronchoalveolar lavage fluid (BALF) was obtained from 15 patients (62.5%) and showed predominantly polymorphonuclear cell infiltration (52%, range of 48%~ 63%). Four patients received transbronchial lung biopsy, and histopathological examinations revealed suppurative pneumonia and organizing pneumonia. The in-hospital mortality rate was 19.4%. Age (odds ratio [OR] 1.100; 95% confidence interval [CI] 1.035-1.169), hypotension (OR 7.260; 95% CI 1.126-46.804) and ineffective or delay of empirical antimicrobial therapy (OR 7.341; 95% CI 1.145-47.045) were found to be independent risk factors for in-hospital mortality, whereas drainage treatment was found to be a protective factor (OR 0.33; 95% CI 0.002-0.677). CONCLUSIONS: SPE cases presented with nonspecific clinical manifestations and radiologic features. Blood cultures and bronchoscopy are important measures for early diagnosis and differential diagnosis. There is relationship between primary infection sites and the type of pathogen. Maintaining normal blood pressure and providing timely and appropriate initial antimicrobial therapy for effective control of the infection could improve prognosis.


Assuntos
Mortalidade Hospitalar , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Choque Séptico/diagnóstico , Choque Séptico/mortalidade , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , China , Cuidados Críticos , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Prognóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/microbiologia , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico , Choque Séptico/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
18.
Catheter Cardiovasc Interv ; 91(1): 9-16, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28303630

RESUMO

OBJECTIVES: To evaluate long-term outcomes in patients undergoing either paclitaxel-eluting stents (PES) or endeavor zotarolimus-eluting stents (E-ZES) placement and to assess comparative effectiveness of PES vs. E-ZES in different "off-label" and "high-risk" patient subgroups. BACKGROUND: PES and E-ZES are frequently used in percutaneous coronary interventions (PCIs). However, the long-term comparative effectiveness of PES vs. E-ZES in real practice is unknown. METHODS: We created a longitudinal database by linking the New York State (NYS) cardiac registries, the NYS hospital discharge file, the National Death Index, and the U.S. Census file for patients undergoing either PES or E-ZES placement from July 2008 through December 2009. All-cause mortality, acute myocardial infarction (AMI), target lesion PCI (TLPCI), and target vessel coronary artery bypass graft (TVCABG) surgery were compared for 9,264 propensity score matched patients for a 5-year follow-up period using the Kaplan-Meier method with further adjustment using Cox proportional hazards regression. RESULTS: We did not detect significant differences between E-ZES and PES (reference) in 5-year mortality (adjusted hazard ratio : 1.02, 95% confidence interval : 0.91-1.14), AMI (AHR: 1.05, 95% CI: 0.90-1.22), TLPCI (AHR: 0.99, 95% CI: 0.86-1.13), and TVCABG (AHR, 1.07, 95% CI: 0.84-1.36). For six "off-label" and two "high-risk" subpopulations, we had similar findings for the two stent groups. CONCLUSION: NYS observational data suggest that 5-year outcomes are comparable in patients receiving either PES or E-ZES placement, mirroring the findings of recent clinical trials. © 2017 Wiley Periodicals, Inc.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos , Infarto do Miocárdio/cirurgia , Paclitaxel/administração & dosagem , Intervenção Coronária Percutânea/instrumentação , Sirolimo/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/efeitos adversos , Pesquisa Comparativa da Efetividade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , New York , Paclitaxel/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Desenho de Prótese , Sistema de Registros , Fatores de Risco , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
19.
Catheter Cardiovasc Interv ; 91(3): 417-424, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28557275

RESUMO

OBJECTIVES: To study four-year outcomes for patients receiving either bare-metal stents (BMS) or everolimus-eluting stents (EES) and to evaluate the comparative effectiveness of BMS versus EES in six "off-label" and two "high-risk" patient subgroups. BACKGROUND: BMS and EES (a second generation of drug-eluting stent) are used in contemporary practice to treat coronary artery disease. However, little is known about long-term comparative effectiveness between BMS and EES. METHODS: Using the New York State (NYS) cardiac registries, statewide hospital discharge data, the National Death Index, and the U.S. Census file, we assessed four-year outcomes of BMS versus EES in patients receiving either BMS or EES from July 2008 through December 2009. The outcomes included all-cause mortality, acute myocardial infarction (AMI), target-lesion PCI (TLPCI), and target-vessel coronary artery bypass graft (TVCABG) surgery for a follow-up period of four years (median follow-up of 3.6 years). We compared 9,290 propensity score matched pairs with further adjustment using Cox proportional hazards regression. RESULTS: Compared with patients receiving BMS, patients receiving EES had a lower rate of four-year mortality (adjusted hazard ratio : 0.58, 95% confidence interval : 0.54-0.63), AMI (AHR: 0.68, 95% CI: 0.61-0.76), TLPCI (AHR: 0.67, 95% CI: 0.60-0.75), and TVCABG (AHR, 0.53, 95% CI: 0.43-0.65). For "off-label" and "high-risk" subgroups, EES was associated with decreased mortality and generally better AMI, TLPCI, and TVCABG outcomes relative to BMS. CONCLUSIONS: Compared with BMS use, EES use was associated with better four-year outcomes.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos , Everolimo/administração & dosagem , Metais , Intervenção Coronária Percutânea/instrumentação , Stents , Idoso , Idoso de 80 Anos ou mais , Pesquisa Comparativa da Efetividade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Desenho de Prótese , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
J Vasc Interv Radiol ; 29(12): 1639-1644, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30414719

RESUMO

PURPOSE: To evaluate the effects of endovascular denervation (EDN) on abdominal cancer pain relief. MATERIALS AND METHODS: From April 2017 to February 2018, 7 cancer patients (2 males and 5 females) were enrolled in this study. The diagnoses of the patients included 3 pancreatic cancer, 2 cervical carcinoma, 1 cholangiocarcinoma, and 1 esophageal cancer with retroperitoneum lymph nodes invasion. Denervation was carried out at the abdominal aorta close to the origin of celiac artery and superior mesenteric artery with the use of a multielectrode radiofrequency ablation catheter with settings of time 120 seconds and temperature 60°C. The primary end point was improvement in pain scores. The secondary end points included change in quality of life, intake of narcotics, and the safety of EDN. RESULTS: All of the patients experienced pain relief. The pain scores as measured by means of visual analog scores at 1, 2, 4, 8, and 12 weeks after the procedure were significantly lower than before the operation (P < .001). A > 4 score reduction was observed in all cases. A significant reduction in narcotics use within 3 months after the operation was also seen. The quality of life scores of the patients improved significantly (P < .005) with better sleep. No severe treatment-related adverse events or major complications were observed. CONCLUSIONS: EDN is a safe and effective means to alleviate pain caused by cancer and may serve as a new approach for cancer pain relief and palliative care.


Assuntos
Neoplasias Abdominais/terapia , Dor Abdominal/prevenção & controle , Denervação Autônoma/métodos , Ablação por Cateter , Plexo Celíaco/cirurgia , Procedimentos Endovasculares/métodos , Neoplasias Abdominais/complicações , Neoplasias Abdominais/diagnóstico , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Adulto , Idoso , Angiografia Digital , Aortografia/métodos , Denervação Autônoma/efeitos adversos , Ablação por Cateter/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Entorpecentes/uso terapêutico , Medição da Dor , Cuidados Paliativos , Projetos Piloto , Dados Preliminares , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento
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