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In this answer, we provide our arguments in support of the possibility to observe the single file-organization of red blood cells in microvessels and the resulting unexpectedly weak increase of blood viscosity with increasing hematocrit, the physiological relevance of which was questioned in the comment. The key element is that the equivalent diameter in 3D for the maximal hematocrit corresponding to a single file of red blood cells is about 10 µm and not 20 µm, as in 2D. In addition, the viscosity contrast (ratio between the cell internal and external viscosities) value must be chosen in our 2D simulation in a such a way that the effective viscosity (a linear combination of the internal, external and membrane viscosities) be close to that of a real RBC. Taking these two facts into account, we find a reasonable agreement between our 2D viscosity simulations data and experimental data, despite the crude 2D assumption.
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Eritrócitos , Reologia , Eritrócitos/citologia , Viscosidade Sanguínea , Humanos , Viscosidade , HematócritoRESUMO
BACKGROUND: The prognostic significance of tumor-infiltrating immune cells in endometrial cancer is a subject of ongoing debate. Recent evidence increasingly suggests that these immune cells and cytokines, abundant in endometrial cancer tissues, play a pivotal role in stimulating the body inherent anti-tumor immune responses. METHODS: Leveraging publicly accessible genetic data, we conducted an exhaustive 2-sample Mendelian randomization (MR) study. This study aimed to explore the causal links between 731 immunophenotypes and the risk of endometrial cancer. We thoroughly assessed the robustness, heterogeneity, and potential horizontal pleiotropy of our findings through extensive sensitivity analyses. RESULTS: Our study identified 36 immunophenotypes associated with endometrial cancer risk. Specific immunophenotypes, such as the percentage of Naive-mature B-cells in lymphocytes (ORâ =â 0.917, 95% CIâ =â 0.863-0.974, Pâ =â .005), and HLA DR expression on CD14-CD16â +â monocytes (ORâ =â 0.952, 95% CIâ =â 0.911-0.996, Pâ =â .032), exhibited a negative correlation with endometrial cancer. Conversely, CD127 expression on CD45RAâ +â CD4â +â in Treg cells (ORâ =â 1.042, 95% CIâ =â 1.000-1.085, Pâ =â .049), and CM CD4+%T in T cell maturation stages (ORâ =â 1.074, 95% CIâ =â 1.012-1.140, Pâ =â .018) showed a positive correlation. Reverse MR analysis linked endometrial cancer to 4 immunophenotypes, including a positive correlation with CD127-CD8br %T cell of Treg (ORâ =â 1.172, 95% CIâ =â 1.080-1.270, Pâ =â .0001), and negative correlations with 3 others, including CM CD4+%T cell (ORâ =â 0.905, 95% CIâ =â 0.832-0.984, Pâ =â .019). CONCLUSION SUBSECTIONS: Our findings underscore a significant causal relationship between immunophenotypes and endometrial cancer in bidirectional MR analyses. Notably, the CM CD4+%T immunophenotype emerged as potentially crucial in endometrial cancer development.
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Neoplasias do Endométrio , Análise da Randomização Mendeliana , Feminino , Humanos , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/imunologia , Imunofenotipagem , Linfócitos do Interstício Tumoral/imunologiaRESUMO
AIM: To analyze the global scientific output concerning myopic traction maculopathy (MTM) and to summarize the research frontiers and hot topics of MTM related researches. METHODS: Data were collected for bibliometric and visualization analyses from Web of Science (WOS) Core Collection. Exported records were analyzed for titles, publication years, research institutions, journal names, authors, keywords, and abstracts using CiteSpace software version 6.1. RESULTS: A total of 839 related studies were analyzed, the publication volume increased annually, with Asia the most active region of MTM research. Optical coherence tomography angiography, optical coherence tomography, macular hole, high myopia, macular buckling were identified as the focus of the current research. Progression, association, classification and shape were identified as the major research frontiers. CONCLUSION: MTM is a major cause of visual loss in pathological myopic eyes. During the preceding 17y, the number of annual publications in MTM research increased gradually. Studies on the progression nature of MTM, genome-wide association study and proper classification of MTM might still be the frontiers of MTM researches.
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The rheological behavior and dynamics of a vesicle suspension, serving as a simplified model for red blood cells, are explored within a Poiseuille flow under the Stokes limit. Investigating vesicle response has led to the identification of novel solutions that complement previously documented forms like the parachute and slipper shapes. This study has brought to light the existence of alternative configurations, including a fully off-centered form and a multilobe structure. The study unveils the presence of two distinct branches associated with the slipper shape. One branch arises as a consequence of a supercritical bifurcation from the symmetric parachute shape, while the other emerges from a saddle-node bifurcation. Notably, the findings are represented through diagrams that display data collapsing harmoniously based on a combination of independent dimensionless parameters. Delving into the rheological implications, a remarkable observation emerges: the normalized viscosity (i.e. similar to intrinsic viscosity) exhibits a non-monotonic trend as a function of vesicle concentration. Initially, the normalized viscosity diminishes as the concentration increases, followed by a subsequent rise at higher concentrations. Noteworthy is the presence of a minimum value in the normalized viscosity at lower concentrations, aligning well with the concentrations observed in microcirculation scenarios. The intricate behavior of the normalized viscosity can be attributed to a delicate spatial arrangement within the suspension. Importantly, this trend echoes the observations made in a linear shear flow scenario, thereby underscoring the universality of the rheological behavior for confined suspensions.
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ATP is not only an energy carrier but also serves as an important signalling molecule in many physiological processes. Abnormal ATP level in blood vessel is known to be related to several pathologies, such as inflammation, hypoxia and atherosclerosis. Using advanced numerical methods, we analysed ATP released by red blood cells (RBCs) and its degradation by endothelial cells (ECs) in a cat mesentery-inspired vascular network, accounting for RBC mutual interaction and interactions with vascular walls. Our analysis revealed a heterogeneous ATP distribution in the network, with higher concentrations in the cell-free layer, concentration peaks around bifurcations and heterogeneity among vessels of the same level. These patterns arise from the spatio-temporal organization of RBCs induced by the network geometry. It is further shown that an alteration of hematocrit and flow strength significantly affects ATP level as well as heterogeneity in the network. These findings constitute a first building block to elucidate the intricate nature of ATP patterns in vascular networks and the far reaching consequences for other biochemical signalling, such as calcium, by ECs.
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Células Endoteliais , Eritrócitos , Células Endoteliais/metabolismo , Velocidade do Fluxo Sanguíneo/fisiologia , Eritrócitos/metabolismo , Microvasos/metabolismo , Trifosfato de Adenosina/metabolismoRESUMO
PURPOSE: The treatment of refractory macular holes is controversial, with human amniotic membrane grafts emerging recently as an attractive option. We performed a meta-analysis and systematic review in this paper to assess the results of human amniotic membrane (hAM) in the treatment of refractory macular hole (MH). METHODS: We searched the Cochrane Database of Systematic Reviews, Web of Science, PubMed, Embase, China National Knowledge Infrastructure databases, VIP database, Wanfang Data Knowledge Service Platform, Sinomed, Chinese Clinical Trial Registry, and Clinical Trials.gov. Studies reporting hAM for the treatment of refractory MH were included. The outcomes are MH closure rate, visual acuity (VA) improvement rate, and graft dislocation/contracture rate. RESULTS: A total of 8 studies on 103 eyes were included, all of which had undergone failed vitrectomy and internal limiting membrane (ILM) peeling. In all studies, the VA improvement rate was 66% (95%CI: 45 to 84%), the MH closure rate was 94% (95%CI: 84 to 100%) and the hAM graft dislocation/contracture rate was 6% (95%CI: 0 to 15%). In the studies using cryopreserved hAM grafts, the MH closure rate was 99% (95%CI: 94 to 100%) and the hAM graft dislocation/contracture rate was 3% (0%, 10%). The VA improvement rates were 94% (95%CI: 79 to 100%) in the retinal detachment subgroup, 37% (95%CI: 20 to 56%) in the pathologic myopia subgroup, and 62% (95%CI: 14 to 100%) in the idiopathic MH subgroup. CONCLUSION: Human amniotic membrane in the treatment of refractory MH results in visual improvement. It has a high macular hole closure rate and low dislocation/contracture rate. Cryopreserved hAM grafts might have better outcomes than dehydrated grafts.
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Descolamento Retiniano , Perfurações Retinianas , Humanos , Âmnio , Membrana Basal/patologia , Membrana Basal/cirurgia , Retina/patologia , Descolamento Retiniano/cirurgia , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Perfurações Retinianas/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Vitrectomia/métodosRESUMO
Transport of deformable particles in a honeycomb network is studied numerically. It is shown that the particle deformability has a strong impact on their distribution in the network. For sufficiently soft particles, we observe a short memory behavior from one bifurcation to the next, and the overall behavior consists in a random partition of particles, exhibiting a diffusionlike transport. On the contrary, stiff enough particles undergo a biased distribution whereby they follow a deterministic partition at bifurcations, due to long memory. This leads to a lateral ballistic drift in the network at small concentration and anomalous superdiffusion at larger concentration, even though the network is ordered. A further increase of concentration enhances particle-particle interactions which shorten the memory effect, turning the particle anomalous diffusion into a classical diffusion. We expect the drifting and diffusive regime transition to be generic for deformable particles.
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Difusão , Transporte BiológicoRESUMO
PURPOSE: To make a propensity-score matching analysis on the clinical application of gastric-jejunum pouch anastomosis (GJPA) and continuous jejunal pouch and residual stomach anastomosis combined with jejunal lateral anastomosis (Contin-L). METHODS: The clinic data of 287 patients who received distal gastrectomy from January 2015 to January 2019 were collected retrospectively. The enrolled patients were divided into the GJPA group and the Contin-L group according to the reconstruction method used. Clinical data and operation complications were analyzed. RESULTS: Compared with Contin-L group, the duration of digestive tract reconstruction in the GJPA group was shorter, and the overall cost in the GJPA group was lower. No obvious intergroup differences were found in other intraoperative data, early surgical outcomes, incidence rates of reflux gastritis, anastomotic ulcer, postoperative nutritional and hematological indicators. The postoperative subjective feelings in the GJPA group were similar with those in the Contin-L groups. CONCLUSION: Addition of jejunal lateral anastomosis is not necessary for GJPA following distal gastrectomy.
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Jejuno , Neoplasias Gástricas , Anastomose em-Y de Roux/métodos , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Jejuno/cirurgia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgiaRESUMO
ATP release by red blood cells (RBCs) under shear stress (SS) plays a pivotal role in endothelial biochemical signaling cascades. The aim of this study is to investigate through numerical simulation how RBC spatiotemporal organization depends on flow and geometrical conditions to generate ATP patterns. Numerical simulations were conducted in a straight channel by considering both plasma and explicit presence of RBCs, their shape deformation and cell-cell interaction, and ATP release by RBCs. Two ATP release pathways through cell membrane are taken into account: pannexin 1 channel, sensitive to SS, and cystic fibrosis transmembrane conductance regulator, which responds to cell deformation. Several flow and hematocrit conditions are explored. The problem is solved by the lattice Boltzmann method. Application of SS to the RBC suspension triggers a nontrivial spatial RBC organization and ATP patterns. ATP localizes preferentially in the vicinity of the cell-free layer close to channel wall. Conditions for maximal ATP release per cell are identified, which depend on vessel size and hematocrit Ht. Increasing further Ht beyond optimum enhances the total ATP release but should degrade oxygen transport capacity, a compromise between an efficient ATP release and minimal blood dissipation. Moreover, ATP is boosted in capillaries, suggesting a vasomotor activity coordination throughout the resistance network.
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Trifosfato de Adenosina , Eritrócitos , Simulação por Computador , Hematócrito , Estresse MecânicoRESUMO
The effect of red blood cells and the undulation of the endothelium on the shear stress in the microvasculature is studied numerically using the lattice Boltzmann-immersed boundary method. The results demonstrate a significant effect of both the undulation of the endothelium and red blood cells on wall shear stress. Our results also reveal that morphological alterations of red blood cells, as occur in certain pathologies, can significantly affect the values of wall shear stress. The resulting fluctuations in wall shear stress greatly exceed the nominal values, emphasizing the importance of the particulate nature of blood as well as a more realistic description of vessel wall geometry in the study of hemodynamic forces. We find that within the channel widths investigated, which correspond to those found in the microvasculature, the inverse minimum distance normalized to the channel width between the red blood cell and the wall is predictive of the maximum wall shear stress observed in straight channels with a flowing red blood cell. We find that the maximum wall shear stress varies several factors more over a range of capillary numbers (dimensionless number relating strength of flow to membrane elasticity) and reduced areas (measure of deflation of the red blood cell) than the minimum wall shear stress. We see that waviness reduces variation in minimum and maximum shear stresses among different capillary and reduced areas.
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Forma Celular , Endotélio Vascular/fisiologia , Eritrócitos/citologia , Microvasos , Estresse MecânicoRESUMO
Transporting water and oil microdroplets is important for applications ranging from water harvesting to biomedical analysis but remains a great challenge. This is due to the amplified contact angle hysteresis and insufficient driving force in the micrometer scale, especially for low-surface energy oil droplets. Coalescence of neighboring droplets, which releases vast additional surface energy, was often required, but its relatively uncontrollable nature brings uncertainties to the droplet motion, and the methodology is not applicable to single droplets. Here we introduce a strategy based on slippery surface with immobilized lubricant menisci to directionally transport microdroplets. By simply mounting hydrogel dots on slippery surface, the raised menisci remotely pump microdroplets via capillary force with high efficiency, regardless of droplet size or surface energy. By proof-of-concept experiments, we demonstrate that our method allows for highly efficient water droplet collection and highly sensitive biomedical analyte detection.
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Óleos , Água , Dimetilpolisiloxanos/química , Hidrogéis , Estudo de Prova de Conceito , Propriedades de SuperfícieRESUMO
ATP is a major player as a signaling molecule in blood microcirculation. It is released by red blood cells (RBCs) when they are subjected to shear stresses large enough to induce a sufficient shape deformation. This prominent feature of chemical response to shear stress and RBC deformation constitutes an important link between vessel geometry, flow conditions, and the mechanical properties of RBCs, which are all contributing factors affecting the chemical signals in the process of vasomotor modulation of the precapillary vessel networks. Several in vitro experiments have reported on ATP release by RBCs due to mechanical stress. These studies have considered both intact RBCs as well as cells within which suspected pathways of ATP release have been inhibited. This has provided profound insights to help elucidate the basic governing key elements, yet how the ATP release process takes place in the (intermediate) microcirculation zone is not well understood. We propose here an analytical model of ATP release. The ATP concentration is coupled in a consistent way to RBC dynamics. The release of ATP, or the lack thereof, is assumed to depend on both the local shear stress and the shape change of the membrane. The full chemo-mechanical coupling problem is written in a lattice-Boltzmann formulation and solved numerically in different geometries (straight channels and bifurcations mimicking vessel networks) and under two kinds of imposed flows (shear and Poiseuille flows). Our model remarkably reproduces existing experimental results. It also pinpoints the major contribution of ATP release when cells traverse network bifurcations. This study may aid in further identifying the interplay between mechanical properties and chemical signaling processes involved in blood microcirculation.
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Trifosfato de Adenosina/metabolismo , Simulação por Computador , Membrana Eritrocítica/fisiologia , Eritrócitos/fisiologia , Modelos Cardiovasculares , Estresse Mecânico , Velocidade do Fluxo Sanguíneo , Eritrócitos/metabolismo , HumanosRESUMO
Here, we describe a simple method to prepare oil-repellent surfaces with inherent reactivity. Liquid-like copolymers with pendant reactive groups are covalently immobilized onto substrates via a sequential layer-by-layer method. The stable and transparent nanocoatings showed oil repellency to a broad range of organic liquids even in the presence of reactive sites. Functional molecules could be covalently immobilized onto the oil-repellent surfaces. Moreover, the liquid repellency can be maintained or finely tailored after post-chemical modification via synergically tailoring the film thickness, selection of capping molecules, and labeling degree of the capping molecules. Oil-repellent surfaces that are capable of post-functionalization would have technical implications in surface coatings, membrane separation, and biomedical and analytical technologies.
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Biofouling caused by the adhesion of respiratory microdroplets generated in sneezing and coughing plays an important role in the spread of many infectious diseases. Although water-repellent surfaces are widely used for the long-term repellency of aqueous solutions, their repellency to pathogen-containing microdroplets is elusive. In this work, microdroplets from picoliter to nanoliter were successfully generated in a controlled manner to mimic the exhaled microdroplets in sneezing and coughing, which allowed us to evaluate the adhesion of microdroplets on both superhydrophobic and lubricant-infused "slippery" surfaces for the first time. The impact and retention of water microdroplets on the two water-repellent surfaces are compared and investigated. Microdroplet-mediated surface biofouling and pathogen transmission were also demonstrated. Our results suggested that the adhesion of microdroplets should be duly considered in the design and application of water-repellent surfaces on biofouling prevention.
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Água/química , Incrustação Biológica , Lubrificantes , Propriedades de SuperfícieRESUMO
BACKGROUND: We explore and compare the advantages and disadvantages of different operating methods for a peripheral iridectomy (PI) for phakic posterior chamber implantable contact lens (ICL) implantation in patients with dark-brown irides. METHODS: Forty-six patients completed this prospective comparative study. Neodymium: yttrium-aluminum-garnet (Nd:YAG) PI was performed in 15 patients (30 eyes) 2 weeks prior to surgery (YAG PI group). Surgical PI was performed in 17 patients (34 eyes) 2 weeks prior to the ICL implantation (preoperative PI group), and intraoperative PI was performed during ICL implantation in 14 patients (28 eyes) (intraoperative PI group). The postoperative recovery of visual acuity, intraoperative complications, operation duration, and patients' visual disturbances were compared. RESULTS: Compared with the preoperative BCVA, the uncorrected visual acuity (UCVA) at 1 week was markedly restored in the preoperative PI group (P = 0.004). UCVA in the three groups of patients had all recovered well at 1 and 3 months after ICL implantation and were significantly better than the preoperative BCVA (all P < 0.01). In the YAG PI group, iris bleeding occurred in nine eyes (30.0 %) and 14 eyes (46.7 %) had pigment dispersion; these values were significantly higher than those in the preoperative PI group (5.9 and 14.7 %, respectively, both P = 0.01). In the intraoperative PI group, elevated high intraocular pressure occurred in four eyes (14.3 %), and eight eyes (28.6 %) had varying degrees of pigment dispersion after ICL implantation. CONCLUSIONS: For patients with dark-brown irides, surgical PI performed 2 weeks prior to the implantation facilitated better postoperative recovery of visual acuity. TRIAL REGISTRATION: Current Controlled Trials ISRCTN35178162 . Retrospectively registered March 4th, 2013.
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Cor de Olho , Iridectomia/métodos , Iris/cirurgia , Implante de Lente Intraocular/métodos , Miopia Degenerativa/cirurgia , Lentes Intraoculares Fácicas , Adulto , Alumínio , Análise de Variância , Feminino , Humanos , Masculino , Estudos Prospectivos , Acuidade Visual , Adulto Jovem , ÍtrioRESUMO
The human hand is considered to be the terminus of the nervous system. It contains numerous capillary vessels, and it plays an important role in the regulation of the autonomic nervous system. We have used infrared thermography and ultrasound Doppler flowmetry to investigate characteristics of the temperature variation of the hand and the blood flow after cold stimuli. We have also developed an image processing algorithm to measure temperature of various parts of the hand via sequential thermal images. Measured results show that local cold stimuli will induce oscillation of temperature, which may be due to neuroregulation during rewarming. Finally, in order to explain the mechanism of autonomic nervous system (ANS) regulation we have developed an ANS regulation model on the basis of the knowledge of the physiology and bioheat transfer. The results computed using our model are in good agreement with the experimental results.