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The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This investigation seeks to elucidate the correlation between the material composition and structural attributes of these polymer brushes in preventing protein adhesion. To achieve this goal, we modeled three different zwitterionic brushes, namely, carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl)-phosphorylcholine (MPC). The simulations revealed that elevating the grafting density enhances the structural stability, hydration strength, and resistance to protein adhesion exhibited by the polymer brushes. PCBMA manifests a more robust hydration layer, while PMPC demonstrates the slightest interaction with proteins. In a comprehensive evaluation, PSBMA polymer brushes emerged as the best choice with superior stability, enhanced protein repulsion, and minimally induced protein deformation, resulting in effective resistance to nonspecific adhesion. The high-density SBMA polymer brushes significantly reduce the level of protein adhesion in AFM testing. In addition, we have pioneered the quantitative characterization of hydration repulsion in polymer brushes by analyzing the hydration repulsion characteristics at different materials and graft densities. In summary, our study provides a nuanced understanding of the material and structural determinants influencing the capacity of zwitterionic polymer brushes to thwart protein adhesion. Additionally, it presents a quantitative elucidation of hydration repulsion, contributing to the advancement and application of antifouling polymer brushes.
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Polímeros , Proteínas , Polímeros/química , Fenómenos Físicos , Adsorción , Metacrilatos/químicaRESUMEN
High-performance catheters are essential for interventional surgeries, requiring reliable anti-adhesive and lubricated surfaces. This article develops a strategy for constructing high-density sulfobetaine zwitterionic polymer brushes on the surface of catheters, utilizing dopamine and sodium alginate as the primary intermediate layers, where dopamine provides mussel-protein-like adhesion to anchor the polymer brushes to the catheter surface. Hydroxyl-rich sodium alginate increases the number of grafting sites and improves the grafting mass by more than 4 times. The developed high-density zwitterionic polymer brushes achieve long-lasting and effective lubricity (µ<0.0078) and are implanted in rabbits for four hours without bio-adhesion and thrombosis in the absence of anticoagulants such as heparin. Experiments and molecular dynamics simulations demonstrate that graft mass plays a decisive role in the lubricity and anti-adhesion of polymer brushes, and it is proposed to predict the anti-adhesion of polymer brushes by their lubricity to avoid costly and time-consuming bioassays during the development of amphoteric polymer brushes. A quantitative influence of hydration in the anti-adhesion properties of amphiphilic polymer brushes is also revealed. Thus, this study provides a new approach to safe, long-lasting lubrication and anticoagulant surface modification for medical devices in contact with blood. STATEMENT OF SIGNIFICANCE: High friction and bioadhesion on medical device surfaces can pose a significant risk to patients. In response, we have developed a safer, simpler, and more application-specific surface modification strategy that addresses both the lubrication and anti-bioadhesion needs of medical device surfaces. We used dopamine and sodium alginate as intermediate layers to drastically increase the grafting density of the zwitterionic brushes and enabled the modified surfaces to have an extremely low coefficient of friction (µ = 0.0078) and to remain non-bioadhesive for 4 hours in vivo. Furthermore, we used molecular dynamics simulations to gain insight into the mechanisms behind the superior anti-adhesion properties of the high-density polymer brushes. Our work contributes to the development and application of surface-modified coatings.
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Fibrinolíticos , Polímeros , Animales , Humanos , Conejos , Polímeros/farmacología , Dopamina , Lubrificación , Propiedades de Superficie , Alginatos/farmacologíaRESUMEN
Thrombosis of extracorporeal circuits causes significant morbidity and mortality worldwide. In this study, plasma treatment technology and chemical grafting method were used to construct heparinized surfaces on the PVC substrate, which could not only reduce thrombosis but also decrease the side effects of the direct injection of anticoagulants. The PVC substrate was modified by plasma treatment technology firstly to obtain the active surface with the hydroxyl groups used for grafting. Then, heparin was grafted onto the modified PVC surface using different grafting strategies to prepare different heparinized surfaces. The experimental results indicated that the sodium alginate (SA) and carboxymethyl chitosan (CCS) used as interlayers could significantly increase the graft density of heparin to improve the anticoagulant effects and hemocompatibility of heparinized surfaces. In addition, the modification of heparin can further improve the anticoagulant effects. The CCS/low-molecular-weight heparin (LWMH) surface has the best anticoagulant properties, which can prolong the activated partial thromboplastin time (APTT) values of human plasma for about 35 s, reduce the hemolysis rates to <0.3 %, and perform well in the in-vitro blood circulation test. The heparinized surfaces prepared in this work have great application potential in anticoagulant treatment for medical devices.
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Quitosano , Trombosis , Humanos , Heparina/farmacología , Heparina/química , Cloruro de Polivinilo , Quitosano/química , Alginatos , Anticoagulantes/farmacología , Anticoagulantes/química , Tiempo de Tromboplastina ParcialRESUMEN
The lubrication modification of biomedical devices significantly enhances the functionality of implanted interventional medical devices, thereby providing additional benefits for patients. Polymer brush coating provides a convenient and efficient method for surface modification while ensuring the preservation of the substrate's original properties. The current research has focused on a "trial and error" method to finding polymer brushes with superior lubricity qualities, which is time-consuming and expensive, as obtaining effective and long-lasting lubricity properties for polymer brushes is difficult. This review summarizes recent research advances in the biomedical field in the design, material selection, preparation, and characterization of lubricating and antifouling polymer brushes, which follow the polymer brush development process. This review begins by examining various approaches to polymer brush design, including molecular dynamics simulation and machine learning, from the fundamentals of polymer brush lubrication. Recent advancements in polymer brush design are then synthesized and potential avenues for future research are explored. Emphasis is placed on the burgeoning field of zwitterionic polymer brushes, and highlighting the broad prospects of supramolecular polymer brushes based on host-guest interactions in the field of self-repairing polymer brush applications. The review culminates by providing a summary of methodologies for characterizing the structural and functional attributes of polymer brushes. It is believed that a development approach for polymer brushes based on "design-material selection-preparation-characterization" can be created, easing the challenge of creating polymer brushes with high-performance lubricating qualities and enabling the on-demand creation of coatings. STATEMENT OF SIGNIFICANCE: Biomedical devices have severe lubrication modification needs, and surface lubrication modification by polymer brush coating is currently the most promising means. However, the design and preparation of polymer brushes often involves "iterative testing" to find polymer brushes with excellent lubrication properties, which is both time-consuming and expensive. This review proposes a polymer brush development process based on the "design-material selection-preparation-characterization" strategy and summarizes recent research advances and trends in the design, material selection, preparation, and characterization of polymer brushes. This review will help polymer brush researchers by alleviating the challenges of creating polymer brushes with high-performance lubricity and promises to enable the on-demand construction of polymer brush lubrication coatings.
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Simulación de Dinámica Molecular , Polímeros , Humanos , Polímeros/química , Prótesis e ImplantesRESUMEN
Acute pulmonary embolism (APE) with ST-segment elevation and an upward T-wave is rare, and only a few cases have been reported to date. We herein present a case involving a man in his early 70s with an 8-hour history of dyspnea. Serial electrocardiography (ECG) demonstrated ST-segment elevation in leads V1 to V3 with an upward T-wave, laboratory tests revealed a high serum concentration of high-sensitivity cardiac troponin I, and signs of acute myocardial infarction were present. However, emergency coronary angiography revealed normal coronary arteries. A subsequent computed tomography scan of the pulmonary arteries showed findings consistent with APE. The patient's chest tightness was relieved after catheter-directed thrombolysis. Postoperative ECG showed that the ST-segment in leads V1 to V3 had fallen back and that the T-wave was inverted. The patient was discharged on rivaroxaban therapy. Clinically, the ECG findings of ST-segment elevation and an upward T-wave in APE can be easily misdiagnosed as acute myocardial infarction. Physicians should maintain clinical suspicion through risk stratification to identify APE.
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Hominidae , Infarto del Miocardio , Embolia Pulmonar , Infarto del Miocardio con Elevación del ST , Masculino , Humanos , Animales , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio/diagnóstico , Electrocardiografía , Enfermedad Aguda , Embolia Pulmonar/diagnóstico por imagen , BiomarcadoresRESUMEN
OBJECTIVE: Previous studies showed that the combination of bevacizumab and erlotinib (combination therapy) significantly prolonged progression-free survival (PFS) but no overall survival (OS) compared to erlotinib alone (monotherapy) for advanced EGFR-mutant non-small cell lung cancer (NSCLC). Two phase III randomized controlled trials (RCTs) had reported the OS results in 2021. This meta-analysis aimed to include the results of the two RCTs to make a decision. MATERIALS AND METHODS: We systematically searched relevant databases for RCTs on the use of bevacizumab plus erlotinib in advanced EGFR-mutant NSCLC. The main outcomes of interest were PFS, OS, and the reported hazard ratio (HR). Fixed-effect model was used to estimate pooled HR. RESULTS: Total 5 RCTs with 935 patients were eligible for this meta-analysis. All studies reached their primary study endpoints including PFS and OS. Compared to monotherapy, combination therapy remarkably prolonged PFS (HR = 0.60, 95% confidence interval CI 0.51-0.70; p < 0.00001); however, OS was similar between the two groups (HR = 0.90, 95% CI 0.76-1.08; p = 0.26). Subgroup analysis demonstrated that in deletion within exon 19 (19del) mutation subgroup, the combination therapy could only prolong PFS (HR = 0.60, 95% CI 0.47-0.76; p < 0.0001) but not OS (HR = 1.00, 95% CI 0.73-1.37; p = 1.00), and also in leucine-to-arginine substitution in exon 21 (L858R) mutation subgroup (HR = 0.59, p < 0.0001 and HR = 0.80, p = 0.18, respectively). For patients with brain metastasis at baseline, the combination therapy achieved a significant better PFS than the monotherapy (HR = 0.60, 95% CI 0.39-0.90; p = 0.01), and a better OS with the difference marginally significant (HR = 0.69, 95% CI 0.46-1.02; p = 0.06). CONCLUSIONS: Combination of bevacizumab and erlotinib can prolong progression-free survival but not overall survival compared to erlotinib alone in advanced EGFR-mutant non-small cell lung cancer patients. The combination therapy not only can prolong progression-free survival but also has a tendency to prolong overall survival for patients with brain metastasis at baseline.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Bevacizumab/uso terapéutico , Clorhidrato de Erlotinib/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genéticaRESUMEN
INTRODUCTION: Allergic rhinitis is a global health problem that can potentially be managed through acupressure. Our clinical observations have identified Allergic Rhinitis Acupressure Therapeutic (ARAT) as a novel acupressure treatment acting on specific acupoints, which may enhance the effectiveness of acupressure. Therefore, we propose a three-arm randomized controlled trial will be conducted to investigate the efficacy and safety of ARAT for perennial allergic rhinitis (PAR). METHODS/DESIGN: In this trial, eligible 111 participants diagnosed with PAR will be randomly assigned to one of three groups: the ARAT group, the non-specific acupoints group, or the blank control group. The primary outcome will be the change in the total nasal symptom score, and the secondary outcomes will include: 1) changes in the scores of the standard version of Rhinoconjunctivitis Quality of Life Questionnaire (RQLQs); 2) acoustic rhinometry and anterior rhinomanometry; 3) changes in the scores of relief medication usage; 4) incidence of adverse events. Additionally, we will measure and compare the changes in cytokine levels (IL-5, IL-13, IFN-γ, and TSLP) in nasal secretions. The RQLQs and primary outcomes will be assessed at the beginning, middle, and end stages of the treatment period, with monthly follow-ups conducted over a total of three months. The secondary outcomes and biomarkers in nasal secretions will be measured at the beginning and end of the treatment period. Any adverse events or need for rescue medication will be carefully noted and recorded. DISCUSSION: This study may produce a new acupressure treatment prescription that is easy to learn, more targeted, and adaptable. This trial represents the first clinical investigation comparing ARAT treatment for PAR with the non-specific acupoints group and blank control group. Our data is expected to provide evidence demonstrating the safety and efficacy of ARAT for PAR patients, while also exploring the functional mechanism underlying ARAT treatment, moreover, the results offer valuable insights for healthcare professionals in managing PAR symptoms. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2300072292. Registered on June 08, 2023.
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Acupresión , Rinitis Alérgica , Humanos , Calidad de Vida , Mucosa Nasal , Rinitis Alérgica/terapia , Puntos de Acupuntura , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
We designed a versatile optical edge detection setup with two cascaded Pancharatnam-Berry lenses (PBLs) placed at the Fourier plane of a 4f system. When the two PBLs are parallel and close to each other, owing to the moiré-like effect, one-dimensional edge detection with adjustable resolution is achieved by introducing a transverse displacement of one PBL. Furthermore, two-dimensional edge detection with adjustable resolution can also be realized by tuning the longitudinal distance between the PBLs, and the transverse displacement is exploited to adjust the edge resolution in specified directions. The proposed scheme is verified by a proof-of-principle experiment in which the resolution-adjustable edges of different targets and cells were clearly observed, showing its flexibility and potential application in image processing and high-contrast microscopy.
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Cristalino , Lentes , Procesamiento de Imagen Asistido por Computador , MicroscopíaRESUMEN
Inflammation and dyslipidemia underlie the pathological basis of atherosclerosis (AS). Clinical studies have confirmed that there is still residual risk of atherosclerotic cardiovascular diseases (ASCVD) even after intense reduction of LDL. Some of this residual risk can be explained by inflammation as anti-inflammatory therapy is effective in improving outcomes in subjects treated with LDL-lowering agents. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation is closely related to early-stage inflammation in AS. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme of toxic aldehyde metabolism located in mitochondria and works in the metabolism of toxic aldehydes such as 4-HNE and MDA. Despite studies confirming that ALDH2 can negatively regulate NLRP3 inflammasome and delay the development of atherosclerosis, the mechanisms involved are still poorly understood. Reactive Oxygen Species (ROS) is a common downstream pathway activated for NLRP3 inflammasome. ALDH2 can reduce the multiple sources of ROS, such as oxidative stress, inflammation, and mitochondrial damage, thereby reducing the activation of NLRP3 inflammasome. Further, according to the downstream of ALDH2 and the upstream of NLRP3, the molecules and related mechanisms of ALDH2 on NLRP3 inflammasome are comprehensively expounded as possible. The potential mechanism may provide potential inroads for treating ASCVD.
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BACKGROUND: Double blood supply to the anterior descending artery is a rare finding of coronary angiography. However, infective endocarditis (IE) combined with anomalous double blood supply to the anterior descending artery has not been reported. CASE PRESENTATION: A 58-year-old male previously diagnosed with IE came to the emergency department with complaints of chest tightness and dyspnea. Further examination confirmed severe aortic valve regurgitation combined with IE and anomalous double blood supply to the anterior descending artery. The cardiopulmonary bypass surgery was performed by direct perfusion through the normal left and right coronary openings. After surgery, the heart started beating again normally without any cardiogenic ischemic events. CONCLUSION: Cardiopulmonary bypass by direct perfusion was safe in the patient with anomalous double blood supply to the anterior descending artery.
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Endocarditis Bacteriana , Endocarditis , Masculino , Humanos , Persona de Mediana Edad , Arterias , Corazón , Angiografía CoronariaRESUMEN
BACKGROUND: Patients in disaster areas require the most urgent assistance. In recent large-scale natural disasters, intensive care nurses have served as an important reserve component of disaster response teams. In disaster nursing, ability and attitude directly affect the quality and effectiveness of disaster rescues. However, few studies have examined the disaster nursing competency of intensive care nurses in China. PURPOSE: This study was designed to describe the current status of disaster nursing competency among intensive care nurses, analyze the related factors affecting the disaster response effectiveness, and evaluate the values of disaster nursing continuing education and training in cultivating professional personnel with disaster emergency rescue competence. METHODS: This cross-sectional study was conducted at six tertiary general government hospitals in Jinan, Shandong Province, China. A convenience sampling method was adopted, and the Wenjuanxing website was used to compile the network questionnaire, which participants completed via a WeChat group. Descriptive, correlation, and regression analyses were performed using SPSS software. RESULTS: The participants in this study included 285 registered intensive care nurses employed at six hospitals in Jinan. Most were female (77.9%), and the mean age was 29.9 years. The mean total disaster nursing ability score was 122.98 (SD = 31.70), and the average scores for each item ranged from 2.78 to 3.70. The incident command system item earned the highest mean score (3.70, SD = 1.22), followed by triage (3.24, SD = 0.93). The biological preparedness item earned the lowest mean score (2.78, SD = 1.04). Being male, being < 30 years old, having an understanding of disaster nursing, having previously participated in disaster emergency simulation drills or training, and having a higher self-evaluation of rescue competence were all associated with higher disaster-nursing knowledge scores. Multiple linear regression analyses indicated that understanding of disaster nursing and experience participating in disaster emergency rescue drills or training had the most significant influence on the disaster nursing emergency knowledge score, followed by positive self-evaluation of disaster nursing ability and demand for training. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings of this study indicate that the participants had a moderate disaster-nursing competency and that this competency may be improved through disaster-related continuing education and training. The cognitive attitude of disaster nursing was found to correlate positively with self-efficacy. Simulated emergency drills may effectively improve the disaster nursing competency of critical care nurses. The findings emphasize that experiences other than direct clinical practice such as specialized simulated emergency drills and training as well as willingness for such training are stronger factors for identifying and developing overall disaster nursing competency.
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Desastres , Enfermeras y Enfermeros , Adulto , China , Competencia Clínica , Cuidados Críticos , Estudios Transversales , Femenino , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
Introduction: Objectives: this study aimed to evaluate the relationship of Nutritional Risk Screening 2002 (NRS2002) and in-hospital major adverse cardiac events (MACE) in patients with severe heart failure. Methods: an observational study was conducted at the emergency intensive care units (EICU) of Shandong University Qilu Hospital from January 2017 to December 2019. Nutritional screening and assessment were performed at the time of admission to hospital with the NRS2002. Results: of the 209 patients included, 16 cases (7.66 %) were not at nutritional risk, and 193 cases (92.34 %) were at risk. Among them, 12 cases (5.74 %) were malnourished, 38 cases (18.18 %) were at high nutritional risk, and 115 cases (55.02 %) were overweight and obese. The differences in prealbumin (PA) and N-terminal B-type natriuretic peptide precursor (NT-proBNP) between the 2 groups were statistically significant (p < 0.05). A total of 134 cases (64.12 %) received nutrition treatment support, of which 39 cases (29.10 %) received enteral nutrition (EN), 77 cases (57.46 %) parenteral nutrition, and 18 cases (13.43 %) enteral nutrition combined with parenteral nutrition (EN + SPN) support treatment. In all, 31 cases (54.39 %) reached 100 % of the target dose. Patients in the EN and EN + SPN groups had 37 MACE (64.91 %) and 31 enteral nutrition complications (54.39 %), with differences between the 3 groups being statistically significant (p < 0.05). Conclusion: the nutritional risk of patients with severe heart failure is high, and age and heart function are positively correlated with nutritional risk. The complications rate of patients with high nutritional risk is significantly higher than in those with low risk; the higher the nutritional risk, the higher the hospital mortality rate - that is, nutritional risk affects disease outcome.
Introducción: Objetivos: este estudio tuvo como objetivo evaluar la relación del Nutritional Risk Screening 2002 (NRS2002) con los eventos cardiacos adversos mayores intrahospitalarios (MACE) en pacientes con insuficiencia cardiaca grave. Métodos: se realizó un estudio observacional en las unidades de cuidados intensivos de emergencia (UCIE) del Hospital Qilu de la Universidad de Shandong desde enero de 2017 a diciembre de 2019. Se realizaron un cribado y una evaluación nutricional en el momento del ingreso hospitalario con el NRS2002. Resultados: de los 209 pacientes incluidos, 16 casos (7,66 %) no tenían riesgo nutricional y 193 casos (92,34 %) sí lo tenían. Entre ellos, 12 casos (5,74 %) estaban desnutridos, 38 casos (18,18 %) tenían un alto riesgo nutricional y 115 casos (55,02 %) tenían sobrepeso u obesidad. Las diferencias de prealbúmina (PA) y precursor del péptido natriurético de tipo B N-terminal (NT-proBNP) entre los 2 grupos fueron estadísticamente significativas (p < 0,05). En total, 134 casos (64,12 %) recibieron soporte de tratamiento nutricional, de los que 39 casos (29,10 %) recibieron nutrición enteral (NE), 77 casos (57,46 %) nutrición parenteral y 18 casos (13,43 %) nutrición enteral combinada con nutrición parenteral (NE + SPN) como tratamiento de apoyo. Treinta y un casos (54,39 %) alcanzaron la dosis objetivo al 100 %. Los pacientes de los grupos EN y EN + SPN tuvieron 37 MACE (64,91 %) y 31 complicaciones de la nutrición enteral (54,39 %), siendo la diferencia entre los 3 grupos estadísticamente significativa (p < 0,05). Conclusiones: el riesgo nutricional de los pacientes con insuficiencia cardíaca grave es alto; la edad y la función cardiaca se correlacionan positivamente con el riesgo nutricional. La complicación de los pacientes con alto riesgo nutricional es significativamente mayor que la de los de bajo riesgo; cuanto mayor es el riesgo nutricional, mayor es la tasa de mortalidad hospitalaria, es decir, el riesgo nutricional afecta el resultado de la enfermedad.
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Insuficiencia Cardíaca , Estado Nutricional , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Hospitales , Humanos , Evaluación Nutricional , Estudios ProspectivosRESUMEN
The optical vortex has already found lots of applications in various domains. Among such applications, the precise and quantitative mode analysis of optical vortices is of great significance. In this work, we experimentally validate a simple method to analyze the mode of an already known optical field with collinear holography based on the phase-shifting technology. Further, we propose a ring interference strategy to improve the accuracy of mode analysis. In the proof-of-concept experiment, the complex amplitude is characterized, and the mode purity is well analyzed. This method has excellent accuracy and rapidity, which can be implemented in micro-manipulation, optical communication, and rotation speed measurement based on the rotating Doppler effect.
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Background Ischemia/reperfusion (I/R) injury causes overproduction of reactive oxygen species, which are the major culprits of oxidative stress that leads to inflammation, apoptosis, myocardial damage, and dysfunction. Bilirubin acts as a potent endogenous antioxidant that is capable of scavenging various reactive oxygen species. We have previously generated bilirubin nanoparticles (BRNPs) consisting of polyethylene glycol-conjugated bilirubin. In this study, we examined the therapeutic effects of BRNPs on myocardial I/R injury in mice. Methods and Results In vivo imaging using fluorophore encapsulated BRNPs showed BRNPs preferentially targeted to the site of I/R injury in the heart. Cardiac I/R surgery was performed by first ligating the left anterior descending coronary artery. After 45 minutes, reperfusion was achieved by releasing the ligation. BRNPs were administered intraperitoneally at 5 minutes before and 24 hours after reperfusion. Mice that received BRNPs showed significant improvements in their cardiac output, assessed by echocardiogram and pressure volume loop measurements, compared with the ones that received vehicle treatment. BRNPs treatment also significantly reduced the myocardial infarct size in mice that underwent cardiac I/R, compared with the vehicle-treatment group. In addition, BRNPs effectively suppressed reactive oxygen species and proinflammatory factor levels, as well as the amount of cardiac apoptosis. Conclusions Taken together, BRNPs could exert their therapeutic effects on cardiac I/R injury through attenuation of oxidative stress, apoptosis, and inflammation, providing a novel therapeutic modality for myocardial I/R injury.
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Infarto del Miocardio , Daño por Reperfusión Miocárdica , Nanopartículas , Animales , Apoptosis , Bilirrubina , Inflamación , Ratones , Daño por Reperfusión Miocárdica/prevención & control , Estrés Oxidativo , Especies Reactivas de OxígenoRESUMEN
Mortality and morbidity after cardiac arrest remain high due to ischemia/reperfusion (I/R) injury causing multi-organ damages, even after successful return of spontaneous circulation. We previously generated H2O2-activatable antioxidant nanoparticles formulated with copolyoxalate containing vanillyl alcohol (PVAX) to prevent I/R injury. In this study, we examined whether PVAX could effectively reduce organ damages in a rat model of whole-body ischemia/reperfusion injury (WBIR). To induce a cardiac arrest, 70µl/100 g body weight of 1 mmol/l potassium chloride was administered via the jugular venous catheter. The animals in both the vehicle and PVAX-treated groups had similar baseline blood pressure. After 5.5 minutes of cardiac arrest, animals were resuscitated via intravenous epinephrine followed by chest compressions. PVAX or vehicle was injected after the spontaneous recovery of blood pressure was noted, followed by the same dose of second injection 10 minutes later. After 24 hours, multiple organs were harvested for pathological, biochemical, molecular analyses. No significant difference on the restoration of spontaneous circulation was observed between vehicle and PVAX groups. Analysis of organs harvested 24 hours post procedure showed that whole body I/R significantly increased reactive oxygen species (ROS) generation, inflammatory markers, and apoptosis in multiple organs (heart, brain, and kidney). PVAX treatment effectively blocked ROS generation, reduced the elevation of pro-inflammatory cytokines, and decreased apoptosis in these organs. Taken together, our results suggest that PVAX has potent protective effect against WBIR induced multi-organ injury, possibly by blocking ROS-mediated cell damage.
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Antioxidantes/farmacología , Peróxido de Hidrógeno/farmacología , Nanopartículas/química , Daño por Reperfusión/prevención & control , Animales , Antioxidantes/administración & dosificación , Alcoholes Bencílicos/química , Modelos Animales de Enfermedad , Femenino , Peróxido de Hidrógeno/administración & dosificación , Mediadores de Inflamación , Masculino , Insuficiencia Multiorgánica/prevención & control , Nanopartículas/administración & dosificación , Polímeros/química , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/antagonistas & inhibidoresRESUMEN
Oxidized low-density lipoprotein (ox-LDL)-mediated NLRP3 inflammasome activation is crucial in atherosclerosis (AS) initiation and progression. Aldehyde dehydrogenase 2 (ALDH2) has been reported to display protective effects during AS development; however, the underlying mechanisms are largely unknown. Here we investigate the role of ALDH2 in ox-LDL-induced NLRP3 inflammasome priming and activation. We treated RAW264.7 murine macrophages with ox-LDL with or without ALDH2 activator Alda-1 and measured NLRP3 inflammasome priming and activation, ALDH2 protein expression and enzyme activity, IL-1ß release, and DNA damage. It was found that ox-LDL impaired ALDH2 activity and induced NLRP3 inflammasome priming and activation. Alda-1 inhibited both of the priming and activation steps of NLRP3 inflammasome as well as subsequent cell pyroptosis and attenuated ROS and 4-HNE levels in ox-LDL-treated macrophages. Taken together, ALDH2 activation inhibits priming and activation of NLRP3 inflammasome via reducing oxidative stress, which suggests that ALDH2 may be a potential target for anti-inflammatory therapies in AS treatment.
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Aldehído Deshidrogenasa Mitocondrial/genética , Antiinflamatorios/farmacología , Benzamidas/farmacología , Benzodioxoles/farmacología , Inflamasomas/efectos de los fármacos , Lipoproteínas LDL/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Aldehído Deshidrogenasa Mitocondrial/metabolismo , Aldehídos/antagonistas & inhibidores , Aldehídos/metabolismo , Animales , Caspasa 1/genética , Caspasa 1/metabolismo , Daño del ADN , Regulación de la Expresión Génica , Humanos , Inflamasomas/metabolismo , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipoproteínas LDL/farmacología , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Estrés Oxidativo/efectos de los fármacos , Piroptosis/efectos de los fármacos , Piroptosis/genética , Células RAW 264.7 , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
Using camera sensors for ground robot Simultaneous Localization and Mapping (SLAM) has many benefits over laser-based approaches, such as the low cost and higher robustness. RGBD sensors promise the best of both worlds: dense data from cameras with depth information. This paper proposes to fuse RGBD and IMU data for a visual SLAM system, called VINS-RGBD, that is built upon the open source VINS-Mono software. The paper analyses the VINS approach and highlights the observability problems. Then, we extend the VINS-Mono system to make use of the depth data during the initialization process as well as during the VIO (Visual Inertial Odometry) phase. Furthermore, we integrate a mapping system based on subsampled depth data and octree filtering to achieve real-time mapping, including loop closing. We provide the software as well as datasets for evaluation. Our extensive experiments are performed with hand-held, wheeled and tracked robots in different environments. We show that ORB-SLAM2 fails for our application and see that our VINS-RGBD approach is superior to VINS-Mono.
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BACKGROUND: The incidence of recurrent cardiovascular events from the progression of nontarget lesions (NTLs) is high for percutaneous coronary intervention-treated patients. However, the underlying mechanisms have not been thoroughly elucidated. METHODS: In this study, ten atherosclerotic rabbits with multiple plaques in the upper and lower segments of abdominal aorta (group A) were randomly divided into two subgroups: group A1 underwent intravascular ultrasound examination and stent implantation in the lower segments of the abdominal aorta (n=5), whereas group A2 was without stenting (n=5). Group B was a control group without balloon injury. The serum levels of high-sensitivity CRP, interleukin-6 (IL-6), oxidized low-density lipoprotein, and CD36 were assessed via ELISA at five time points between the 10th and 18th weeks. The upper abdominal aorta was examined via the immunohistochemical stain and Western blotting of matrix metallopeptidase 9 (MMP-9), CD36, IL-6, and tumor necrosis factor α. RESULTS: As a result, we found that stent implantation aggravated serum levels of CD36, oxidative stress, and inflammatory cytokines. Meanwhile, the upper abdominal arterial plaque burden significantly increased after stenting by intravascular ultrasound. Immunohistochemistry and Western blotting showed that the local NTLs' matrix metallopeptidase 9, CD36, IL-6, and tumor necrosis factor α expressions in group A1 were significantly higher than those in groups A2 and B (P<0.05-0.01). More importantly, a strong correlation was identified between CD36 expression and NTLs' plaque burden before the rabbits were killed. CONCLUSION: Taken together, stent implantation accelerated inflammation, induced oxidative stress, and increased the NTLs' progression, which were associated with the upregulated CD36 expression.
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OBJECTIVE: Intracoronary (IC) glycoprotein IIb/IIIa inhibitors (GPIs) after thrombus aspiration (TA) for patients with ST-segment elevation myocardial infarction (STEMI), as compared with percutaneous coronary interventions (PCI) alone, is still on debate. To address this issue, we performed a meta-analysis of results from prospective or randomized controlled trials on the topic. METHODS: We searched electronic and printed sources (up to June 20, 2016) according to the selection criteria. Data were abstraction and meta-analysis was performed using RevMan 5.3 software. RESULTS: The cohorts involved 14 articles describing 1,918 participants were included. The incidence of the short-term major adverse cardiac events (MACE) was significantly reduced with intracoronary GPIs after TA (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.13 to 0.65, p=0.003). Benefits were noted for short-term mortality (OR: 0.31; 95% CI: 0.17 to 0.57, p=0.0002) and reinfarction (OR: 0.28; 95% CI: 0.10 to 0.78, p=0.01) in subjects who received intracoronary GPIs after TA. Moreover, the Thrombolysis in Myocardial Infarction (TIMI) trial grade 3 postprocedure (OR: 2.29; 95% CI: 1.72 to 3.04, P<0.00001) and complete ST-segment resolution (STR) rate (OR: 2.68; 95% CI: 1.85 to 3.87, P<0.00001) were both improved with intracoronary GPIs after TA. As a result, left ventricular ejection fraction (LVEF) at short-term follow-up showed a significant difference (OR: 7.33; 95% CI: 5.60 to 9.06, p<0.0001) in favor of the TA and intracoronary GPIs administration. CONCLUSIONS: Our study demonstrates that intracoronary GPIs may have a synergistic effect with thrombus aspiration on short-term mortality, reinfarction, and cardiac functional recovery.
RESUMEN
BACKGROUND: Worldwide propagation of minimally invasive surgeries (MIS) is hindered by their drawback of indirect observation and manipulation, while monitoring of surgical instruments moving in the operated body required by surgeons is a challenging problem. Tracking of surgical instruments by vision-based methods is quite lucrative, due to its flexible implementation via software-based control with no need to modify instruments or surgical workflow. METHODS: A MIS instrument is conventionally split into a shaft and end-effector portions, while a 2D/3D tracking-by-detection framework is proposed, which performs the shaft tracking followed by the end-effector one. The former portion is described by line features via the RANSAC scheme, while the latter is depicted by special image features based on deep learning through a well-trained convolutional neural network. RESULTS: The method verification in 2D and 3D formulation is performed through the experiments on ex-vivo video sequences, while qualitative validation on in-vivo video sequences is obtained. CONCLUSION: The proposed method provides robust and accurate tracking, which is confirmed by the experimental results: its 3D performance in ex-vivo video sequences exceeds those of the available state-of -the-art methods. Moreover, the experiments on in-vivo sequences demonstrate that the proposed method can tackle the difficult condition of tracking with unknown camera parameters. Further refinements of the method will refer to the occlusion and multi-instrumental MIS applications.