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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.
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Algoritmos , Programas Informáticos , Animales , Ratones , Neuronas , Neuritas , EncéfaloRESUMEN
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.
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Antineoplásicos , Apoptosis , Proliferación Celular , Quinasa 9 Dependiente de la Ciclina , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Inhibidores de Proteínas Quinasas , Quinasa 9 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 9 Dependiente de la Ciclina/metabolismo , Humanos , Ligandos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Estructura Molecular , Apoptosis/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Descubrimiento de Drogas , Animales , Células HCT116RESUMEN
OBJECTIVE: To evaluate the clinical effectiveness of antibiotic bone cement combined with the lobulated perforator flap based on the descending branch of the lateral circumflex femoral artery (d-LCFA) in the treatment of infected traumatic tissue defects in the foot, in accordance with the Enhanced Recovery after Surgery (ERAS) concept. METHODS: From December 2019 to November 2022, 10 patients with infected traumatic tissue defects of the foot were treated with antibiotic bone cement combined with the d-LCFA lobulated perforator flap. The cohort comprised 6 males and 4 females, aged 21 to 67 years. Initial infection control was achieved through debridement and coverage with antibiotic bone cement, requiring one debridement in nine cases and two debridements in one case. Following infection control, the tissue defects were reconstructed utilizing the d-LCFA lobulated perforator flap, with the donor site closed primarily. The flap area ranged from 12 cm×6 cm to 31 cm×7 cm. Postoperative follow-up included evaluation of flap survival, donor site healing, and ambulatory function of the foot. RESULTS: The follow-up period ranged from 7 to 24 months, averaging 14 months. Infection control was achieved successfully in all cases. The flaps exhibited excellent survival rates and the donor site healed by first intention. Based on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, pain and function were evaluated as excellent in 3 cases, good in 5 cases, and moderate in 2 cases. CONCLUSION: The application of antibiotic bone cement combined with the d-LCFA lobulated perforator flap is an effective treatment for infected traumatic tissue defects of the foot with the advantages of simplicity, high repeatability, and precise curative effects. The application of the d-LCFA lobulated perforator flap in wound repair causes minimal damage to the donor site, shortens hospital stays, lowers medical expenses, and accelerates patient rehabilitation, aligning with the ERAS concept. Therefore, it is a practice worth promoting in clinical use.
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Antibacterianos , Cementos para Huesos , Desbridamiento , Arteria Femoral , Traumatismos de los Pies , Colgajo Perforante , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Colgajo Perforante/irrigación sanguínea , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Traumatismos de los Pies/cirugía , Cementos para Huesos/uso terapéutico , Arteria Femoral/cirugía , Desbridamiento/métodos , Adulto Joven , Procedimientos de Cirugía Plástica/métodos , Resultado del Tratamiento , Traumatismos de los Tejidos Blandos/cirugía , Estudios Retrospectivos , Cicatrización de HeridasRESUMEN
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.
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Antineoplásicos , Chalconas , Neoplasias , Oxadiazoles , Humanos , Relación Estructura-Actividad , Antineoplásicos/química , Ensayos de Selección de Medicamentos Antitumorales , Simulación del Acoplamiento Molecular , Proliferación Celular , Estructura Molecular , Línea Celular Tumoral , Relación Dosis-Respuesta a DrogaRESUMEN
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.
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Bases de Datos de Compuestos Químicos , Simulación del Acoplamiento Molecular , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Inhibidores de Poli(ADP-Ribosa) Polimerasas/química , Evaluación Preclínica de Medicamentos , Humanos , Poli(ADP-Ribosa) Polimerasa-1/química , Relación Estructura-ActividadRESUMEN
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.
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COVID-19 , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/etiología , New York/epidemiología , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
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.
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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.
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Antioxidantes , Células HaCaT , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/química , Estrés Oxidativo , Especies Reactivas de Oxígeno , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/farmacología , Rayos Ultravioleta/efectos adversos , Queratinocitos/metabolismoRESUMEN
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.
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Aprendizaje Profundo , Redes Neurales de la Computación , Marcha , Aceleración , Memoria a Largo PlazoRESUMEN
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.
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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.
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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.
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Antineoplásicos , Artemisininas , Ferroptosis , Humanos , Células MCF-7 , Estructura Molecular , Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Apoptosis , Artemisininas/farmacología , Proliferación Celular , Relación Estructura-Actividad , Línea Celular TumoralRESUMEN
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.
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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.
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Anhidrasa Carbónica IX/antagonistas & inhibidores , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/farmacología , Sulfonamidas/química , Sulfonamidas/farmacología , Antígenos de Neoplasias/metabolismo , Anhidrasa Carbónica IX/metabolismo , Inhibidores de Anhidrasa Carbónica/síntesis química , Línea Celular Tumoral , Células HT29 , Humanos , Simulación del Acoplamiento Molecular , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/metabolismo , Sulfonamidas/síntesis químicaRESUMEN
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.
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Carbohidratos/farmacología , Sulfonamidas/síntesis química , Sulfonamidas/farmacología , Tiadiazoles/síntesis química , Tiadiazoles/farmacología , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Anhidrasas Carbónicas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células HT29 , Humanos , Simulación del Acoplamiento Molecular , Microambiente Tumoral/efectos de los fármacosRESUMEN
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.
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Enfermedad de la Arteria Coronaria/terapia , Evaluación de Procesos y Resultados en Atención de Salud/normas , Intervención Coronaria Percutánea/normas , Reportes Públicos de Datos en Atención de Salud , Garantía de la Calidad de Atención de Salud/normas , Indicadores de Calidad de la Atención de Salud/normas , Anciano , Anciano de 80 o más Años , Cardiólogos/normas , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Bases de Datos Factuales , Femenino , Mortalidad Hospitalaria , Hospitales/normas , Humanos , Masculino , Persona de Mediana Edad , New York , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Sistema de Registros , Retratamiento/normas , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
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Antiinflamatorios no Esteroideos/farmacología , Bencilisoquinolinas/farmacología , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteólisis/prevención & control , Osteoprotegerina/genética , Ligando RANK/genética , Titanio/efectos adversos , Animales , Prótesis Anclada al Hueso , Interfase Hueso-Implante/cirugía , Catepsina D/genética , Catepsina D/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Masculino , Ratones , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patología , Osteogénesis/genética , Osteólisis/inducido químicamente , Osteólisis/genética , Osteólisis/patología , Osteoprotegerina/antagonistas & inhibidores , Osteoprotegerina/metabolismo , Falla de Prótesis/efectos de los fármacos , Ligando RANK/antagonistas & inhibidores , Ligando RANK/metabolismo , Cráneo/efectos de los fármacos , Cráneo/cirugía , Fosfatasa Ácida Tartratorresistente/genética , Fosfatasa Ácida Tartratorresistente/metabolismoRESUMEN
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.
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Mortalidad Hospitalaria , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidad , Choque Séptico/diagnóstico , Choque Séptico/mortalidad , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/mortalidad , Staphylococcus aureus/aislamiento & purificación , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Líquido del Lavado Bronquioalveolar/microbiología , Broncoscopía , China , Cuidados Críticos , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/diagnóstico por imagen , Neumonía/tratamiento farmacológico , Pronóstico , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/microbiología , Estudios Retrospectivos , Choque Séptico/tratamiento farmacológico , Choque Séptico/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
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
Asunto(s)
Fármacos Cardiovasculares/administración & dosificación , Enfermedad de la Arteria Coronaria/cirugía , Stents Liberadores de Fármacos , Infarto del Miocardio/cirugía , Paclitaxel/administración & dosificación , Intervención Coronaria Percutánea/instrumentación , Sirolimus/análogos & derivados , Anciano , Anciano de 80 o más Años , Fármacos Cardiovasculares/efectos adversos , Investigación sobre la Eficacia Comparativa , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , New York , Paclitaxel/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Diseño de Prótesis , Sistema de Registros , Factores de Riesgo , Sirolimus/administración & dosificación , Sirolimus/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
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