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BACKGROUND: Patients with severe stroke often rely on surrogate decision-makers for life-sustaining treatment decisions. We investigated ethnic differences between Mexican Americans (MAs) and non-Hispanic White (NHW) individuals in surrogate reports of physician quality of communication and shared decision-making from the OASIS study (Outcomes Among Surrogate Decision Makers in Stroke) project. METHODS: Patients had ischemic stroke or intracerebral hemorrhage in Nueces County, TX. Surrogates self-identified as being involved in decisions about do-not-resuscitate orders, brain surgery, ventilator, feeding tube, or hospice/comfort care. Surrogate reports of physician quality of communication (scale score, range from 0 to 10) and shared decision-making (CollaboRATE scale score, binary score 1 versus 0) were compared by ethnicity with linear or logistic regression using generalized estimating equations, adjusted for prespecified demographics, clinical factors, and confounders. RESULTS: Between April 2016 and September 2020, 320 surrogates for 257 patients with stroke enrolled (MA, 158; NHW, 85; and other, 14). Overall quality of communication score was better among surrogates of MA patients than NHW individuals after adjustment for demographics, stroke severity, and patient survival though the ethnic difference was attenuated (ß, 0.47 [95% CI, -0.17 to 1.12]; P=0.15) after adjustment for trust in the medical profession and frequency of personal prayer. High CollaboRATE scale scores were more common among surrogates of MA patients than NHW individuals (unadjusted odds ratio, 1.75 [95% CI, 1.04-2.95]). This association persisted after adjustment for demographic and clinical factors though there was an interaction between patient age and ethnicity (P=0.04), suggesting that this difference was primarily in older patients. CONCLUSIONS: Surrogate decision-makers of MA patients generally reported better outcomes on validated measures of quality of communication and shared decision-making than NHW individuals. Further study of outcomes among diverse populations of stroke surrogate decision-makers may help to identify sources of strength and resiliency that may be broadly applicable.
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Tomada de Decisões , Acidente Vascular Cerebral , Humanos , Idoso , Acidente Vascular Cerebral/terapia , Hemorragia Cerebral , Ordens quanto à Conduta (Ética Médica) , TexasRESUMO
The methods for the cross-coupling of aryl(trialkyl)silanes are long-standing challenges due to the extreme inertness of C-Si(R3) bond, though the reaction is environmentally friendly and highly regioselective to synthesize biaryls. Herein, we report a copper-catalyzed cross-coupling of aryl(trialkyl)silanes and aryl via a radical mechanism. The reaction proceeds efficiently with aryl sulfonium salts as limiting reagents, exhibits broad substrate scope, and provides an important synthetic strategy to acquire biaryls, exemplified by unsymmetrical fluorescence probes and late-stage functionalization of drugs. Of note, the experimental and theoretical mechanistic studies revealed a radical mechanism where the copper catalyst and CsF play critical roles on the radical generation and desilylation process.
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BACKGROUND: Adults with type 1 or type 2 diabetes often face financial challenges and other unmet social needs to effective diabetes self-management. OBJECTIVE: Whether a digital intervention focused on addressing socioeconomic determinants of health improves diabetes clinical outcomes more than usual care. DESIGN: Randomized trial from 2019 to 2023. PARTICIPANTS: A total of 600 adults with diabetes, HbA1c ≥ 7.5%, and self-reported unmet social needs or financial burden from a health system and randomized to the intervention or standard care. INTERVENTION: CareAvenue is an automated, e-health intervention with eight videos that address unmet social needs contributing to poor outcomes. MEASURES: Primary outcome was HbA1c, measured at baseline, and 6 and 12 months after randomization. Secondary outcomes included systolic blood pressure and reported met social needs, cost-related non-adherence (CRN), and financial burden. We examined main effects and variation in effects across predefined subgroups. RESULTS: Seventy-eight percent of CareAvenue participants completed one or more modules of the website. At 12-month follow-up, there were no significant differences in HbA1c changes between CareAvenue and control group (p = 0.24). There were also no significant between-group differences in systolic blood pressure (p = 0.29), met social needs (p = 0.25), CRN (p = 0.18), and perceived financial burden (p = 0.31). In subgroup analyses, participants with household incomes 100-400% FPL (1.93 (SE = 0.76), p < 0.01), 201-400% FPL (1.30 (SE = 0.62), p < 0.04), and > 400% FPL (1.27 (SE = 0.64), p < 0.05) had significantly less A1c decreases compared to the control group. CONCLUSIONS: On average, CareAvenue participants did not achieve better A1c lowering, met needs, CRN, or perceived financial burden compared to control participants. CareAvenue participants with higher incomes achieved significantly less A1c reductions than control. Further research is needed on social needs interventions that consider tailored approaches to population subgroups. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov ID NCT03950973, May 2019.
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Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05-0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.
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Twisted-fiber artificial muscles, a new type of soft actuator, exhibit significant potential for use in applications related to lightweight smart devices and soft robotics. Fiber twisting generates internal torque and a spiral architecture, exhibiting rotation, contraction, or elongation as a result of fiber volume change. Untethering a twisted fiber often results in fiber untwisting and loss of stored torque energy. Preserving the torque in twisted fibers during actuation is necessary to realize a reversible and stable artificial muscle performance; this is a key issue that has not yet been systematically discussed and reviewed. This review summarizes the mechanisms for preserving the torque within twisted fibers and the potential applications of such systems. The potential challenges and future directions of research related to twisted-fiber artificial muscles are also discussed.
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Transcranial magnetic stimulation (TMS), a widely used neuroregulatory technique, has been proven to be effective in treating neurological and psychiatric disorders. The therapeutic effect is closely related to the intracranial electric field caused by TMS, thus accurate measurement of the intracranial electric field generated by TMS is of great significance. However, direct intracranial measurement in human brain faces various technical, safety, ethical and other limitations. Therefore, we have constructed a brain phantom that can simulate the electrical conductivity and anatomical structure of the real brain, in order to replace the clinical trial to achieve intracranial electric field measurement. We selected and prepared suitable conductive materials based on the electrical conductivity of various layers of the real brain tissue, and performed image segmentation, three-dimensional reconstruction and three-dimensional printing processes on each layer of tissue based on magnetic resonance images. The production of each layer of tissue in the brain phantom was completed, and each layer of tissue was combined to form a complete brain phantom. The induced electric field generated by the TMS coil applied to the brain phantom was measured to further verify the conductivity of the brain phantom. Our study provides an effective experimental tool for studying the distribution of intracranial electric fields caused by TMS.
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Encéfalo , Estimulação Magnética Transcraniana , Humanos , Encéfalo/fisiologia , Estimulação Magnética Transcraniana/métodos , Cabeça , Mapeamento Encefálico/métodos , Condutividade Elétrica , Campos EletromagnéticosRESUMO
BACKGROUND: The aim of this study was to characterize change in sleep-disordered breathing severity in the year following stroke, overall, and by ethnicity, within the population-based Brain Attack Surveillance in Corpus Christi Project. METHODS: First-ever ischemic strokes (n=414) were ascertained by active and passive surveillance and validated by stroke-trained physicians. Patients with stroke were invited to participate in portable sleep apnea testing (ApneaLink Plus) at baseline and 3, 6, and 12 months poststroke. Sleep-disordered breathing severity was assessed by the respiratory event index (apneas and hypopneas/hour of recording). The component obstructive apnea index and central apnea index were also assessed. Time and ethnicity effects on outcomes, as well as ethnic differences in time effects, were analyzed using generalized estimating equations with multivariable adjustment for confounding factors. RESULTS: Mean age (n=414) was 63.9 years (SD=10.9); 68.4% were Mexican American. Baseline mean respiratory event index, obstructive apnea index, and central apnea index were 21.3 (SD=16.6), 8.6 (SD=11.5), and 1.5 (SD=3.2), respectively. There was no time effect on respiratory event index (P=0.35) but obstructive apnea index increased over time (P<0.01). Averaged over follow-up, respiratory event index and obstructive apnea index were significantly higher in Mexican American than non-Hispanic White persons. No ethnic difference in the time effect was found for either outcome. For central apnea index, there was an ethnicity-time interaction (P=0.01) such that central apnea index increased in non-Hispanic White but did not change in Mexican American persons. CONCLUSIONS: Sleep-disordered breathing severity was significant and stable for most individuals in the year after stroke. These results do not confirm previous reports of diminishing sleep-disordered breathing severity over time after stroke and would support early assessment and treatment where indicated.
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Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Acidente Vascular Cerebral , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/etiologia , EtnicidadeRESUMO
High actuation performance of a moisture actuator highly depends on the presence of a large property difference between the two layers, which may cause interfacial delamination. Improving interfacial adhesion strength while increasing the difference between the layers is a challenge. In this study, a moisture-driven tri-layer actuator with a Yin-Yang-interface (YYI) design is investigated in which a moisture-responsive polyacrylamide (PAM) hydrogel layer (Yang) is combined with a moisture-inert polyethylene terephthalate (PET) layer (Yin) using an interfacial poly(2-ethylhexyl acrylate) (PEA) adhesion layer. Fast and large reversible bending, oscillation, and programmable morphing motions in response to moisture are realized. The response time, bending curvature, and response speed normalized by thickness are among the best compared with those of previously reported moisture-driven actuators. The excellent actuation performance of the actuator has potential multifunctional applications in moisture-controlled switches, mechanical grippers, and crawling and jumping motions. The Yin-Yang-interface design proposed in this work provides a new design strategy for high-performance intelligent materials and devices.
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p-Hydroxyacetophenone (p-HAP) and its glucoside picein are plant-derived natural products that have been extensively used in chemical, pharmaceutical and cosmetic industries owing to their antioxidant, antibacterial and antiseptic activities. However, the natural biosynthetic pathways for p-HAP and picein have yet been resolved so far, limiting their biosynthesis in microorganisms. In this study, we design and construct a biosynthetic pathway for de novo production of p-HAP and picein from glucose in E. coli. First, screening and characterizing pathway enzymes enable us to successfully establish functional biosynthetic pathway for p-HAP production. Then, the rate-limiting step in the pathway caused by a reversible alcohol dehydrogenase is completely eliminated by modulating intracellular redox cofactors. Subsequent host strain engineering via systematic increase of precursor supplies enables production enhancement of p-HAP with a titer of 1445.3 mg/L under fed-batch conditions. Finally, a novel p-HAP glucosyltransferase capable of generating picein from p-HAP is identified and characterized from a series of glycosyltransferases. On this basis, de novo biosynthesis of picein from glucose is achieved with a titer of 210.7 mg/L under fed-batch conditions. This work not only demonstrates a microbial platform for p-HAP and picein synthesis, but also represents a generalizable pathway design strategy to produce value-added compounds.
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Vias Biossintéticas , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Vias Biossintéticas/genética , Glucosídeos/genética , Glucose/genética , Glucose/metabolismo , Engenharia MetabólicaRESUMO
Backgroundï¼Brain arteriovenous malformation (bAVM) is an abnormal vascular mass with disordered arteriovenous connection. Endothelial KRAS mutation is common in bAVM. In vivo studies have demonstrated that mutations of KRAS in somatic cells can induce bAVM-like angiogenesis, suggesting that KRAS gene may play a key role in the development and progression of bAVM. Summaryï¼In this article, we will provide a comprehensive review of action mechanisms of KRAS mutations in the development of bAVM and summarize potential targeting drugs for KRAS mutations in bAVM somatic cells. Key Message: KRAS mutation in human brain endothelial cells is a key driver in the pathogenesis of sporadic cerebral arteriovenous malformations. It is of great clinical importance to explore and summarize the changes in the signaling pathway induced by KRAS mutation, which may provide additional targets for the treatment of sporadic bAVM development.
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In transcranial magnetic stimulation (TMS), the conductivity of brain tissue is obtained by using diffusion tensor imaging (DTI) data processing. However, the specific impact of different processing methods on the induced electric field in the tissue has not been thoroughly studied. In this paper, we first used magnetic resonance image (MRI) data to create a three-dimensional head model, and then estimated the conductivity of gray matter (GM) and white matter (WM) using four conductivity models, namely scalar (SC), direct mapping (DM), volume normalization (VN) and average conductivity (MC), respectively. Isotropic empirical conductivity values were used for the conductivity of other tissues such as the scalp, skull, and cerebrospinal fluid (CSF), and then the TMS simulations were performed when the coil was parallel and perpendicular to the gyrus of the target. When the coil was perpendicular to the gyrus where the target was located, it was easy to get the maximum electric field in the head model. The maximum electric field in the DM model was 45.66% higher than that in the SC model. The results showed that the conductivity component along the electric field direction of which conductivity model was smaller in TMS, the induced electric field in the corresponding domain corresponding to the conductivity model was larger. This study has guiding significance for TMS precise stimulation.
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Imagem de Tensor de Difusão , Estimulação Magnética Transcraniana , Condutividade Elétrica , Eletricidade , Couro CabeludoRESUMO
Transcranial electric stimulation (TES) is a non-invasive, economical, and well-tolerated neuromodulation technique. However, traditional TES is a whole-brain stimulation with a small current, which cannot satisfy the need for effectively focused stimulation of deep brain areas in clinical treatment. With the deepening of the clinical application of TES, researchers have constantly investigated new methods for deeper, more intense, and more focused stimulation, especially multi-electrode stimulation represented by high-precision TES and temporal interference stimulation. This paper reviews the stimulation optimization schemes of TES in recent years and further analyzes the characteristics and limitations of existing stimulation methods, aiming to provide a reference for related clinical applications and guide the following research on TES. In addition, this paper proposes the viewpoint of the development direction of TES, especially the direction of optimizing TES for deep brain stimulation, aiming to provide new ideas for subsequent research and application.
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Estimulação Encefálica Profunda , Estimulação Transcraniana por Corrente Contínua , Estimulação Transcraniana por Corrente Contínua/métodos , Encéfalo/fisiologia , Cabeça , Estimulação Elétrica/métodosRESUMO
Existing neuroregulatory techniques can achieve precise stimulation of the whole brain or cortex, but high-focus deep brain stimulation has been a technical bottleneck in this field. In this paper, based on the theory of negative permeability emerged in recent years, a simulation model of magnetic replicator is established to study the distribution of the induced electric field in the deep brain and explore the possibility of deep focusing, which is compared with the traditional magnetic stimulation method. Simulation results show that a single magnetic replicator realized remote magnetic source. Under the condition of the same position and compared with the traditional method of stimulating, the former generated smaller induced electric field which sharply reduced with distance. By superposition of the magnetic field replicator, the induced electric field intensity could be increased and the focus could be improved, reducing the number of peripheral wires while guaranteeing good focus. The magnetic replicator model established in this paper provides a new idea for precise deep brain stimulation, which can be combined with neuroregulatory techniques in the future to lay a foundation for clinical application.
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Encéfalo , Córtex Cerebral , Simulação por Computador , Eletricidade , Campos MagnéticosRESUMO
PURPOSE: Posterior cerebral artery (PCA) aneurysms are rare. This study is to evaluate the preliminary experience of braided stents applied in PCA aneurysms treatment. METHODS: Angiographic and clinical data of 28 PCA patients treated with braided stents from July 2016 and September 2020 were retrospectively analyzed. RESULTS: A total of 28 PCA aneurysms were enrolled. 22 (78.6%) aneurysms were dissecting aneurysms, while 6 (21.4%) aneurysms were saccular aneurysms. Thirty-five braided stents were implanted with dual stents implanted in 7 cases. Immediate angiographic results show that Raymond class I was obtained in 13 patients (46.4%), Raymond class II was obtained in 4 patients (14.3%), and Raymond class III was obtained in 11 patients (39.3%). Perioperative hemorrhagic events occurred in 1 patient (3.6%). Twenty-four patients (85.7%) received angiographic follow-up, and the mean follow-up time was 11.2 ± 4.9 months. Two patients (8.3%) were confirmed with IA neck recurrence, and 3 patients (12.5%) were confirmed asymptomatic parent artery occlusion (PAO). The other 19 patients were confirmed promoted occlusion with 18 Raymond class I (75%) and 1 Raymond class II (4.2%). Twenty-seven patients (96.4%) received clinical follow-up, and the mean follow-up time was 32.2 ± 13.5 months. One patient (3.7%) confirmed the death event 2 weeks after discharge. The other 27 patients (96.3%) got favorable clinical outcomes with an mRS score of 0-2. CONCLUSIONS: Braided stent-assisted coiling with a high occlusion rate and relatively low complication rate provides an alternative strategy in treating PCA aneurysms. Long-term outcomes need further randomized study with larger case numbers.
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Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Angiografia Cerebral/métodos , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
Electric field stimulation (EFS) can effectively inhibit local Ca 2+ influx and secondary injury after spinal cord injury (SCI). However, after the EFS, the Ca 2+ in the injured spinal cord restarts and subsequent biochemical reactions are stimulated, which affect the long-term effect of EFS. Polyethylene glycol (PEG) is a hydrophilic polymer material that can promote cell membrane fusion and repair damaged cell membranes. This article aims to study the combined effects of EFS and PEG on the treatment of SCI. Sprague-Dawley (SD) rats were subjected to SCI and then divided into control group (no treatment, n = 10), EFS group (EFS for 30 min, n = 10), PEG group (covered with 50% PEG gelatin sponge for 5 min, n = 10) and combination group (combined treatment of EFS and PEG, n = 10). The measurement of motor evoked potential (MEP), the motor behavior score and spinal cord section fast blue staining were performed at different times after SCI. Eight weeks after the operation, the results showed that the latency difference of MEP, the amplitude difference of MEP and the ratio of cavity area of spinal cords in the combination group were significantly lower than those of the control group, EFS group and PEG group. The motor function score and the ratio of residual nerve tissue area in the spinal cords of the combination group were significantly higher than those in the control group, EFS group and PEG group. The results suggest that the combined treatment can reduce the pathological damage and promote the recovery of motor function in rats after SCI, and the therapeutic effects are significantly better than those of EFS and PEG alone.
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Polietilenoglicóis , Traumatismos da Medula Espinal , Animais , Estimulação Elétrica , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/fisiologia , Medula Espinal , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapiaRESUMO
The application of electric field stimulation (EFS) can reduce the cation influx after spinal cord injury. However, regenerated cation influx and reestablished injury potential are observed after EFS. Polyethylene glycol (PEG) is popular as an effective cell membrane fusion agent. This study aims to determine the effects of the combination therapy of EFS and PEG in the ex vivo spinal cord after compression. The ex vivo spinal cords of female rats with compression injury were incubated in a double sucrose gap recording chamber (DSGRC) and randomly divided into the following four groups: (1) compression group: compression only, (2) EFS group: EFS for 15 min, (3) PEG group: PEG treatment for 4 min, and (4) EFS + PEG group: EFS for 15 min and PEG treatment for 4 min. The hematoxylin-eosin staining was performed to measure the necrotic area of the spinal cords. The gap potential was detected, and the area under the curve of the gap potential was calculated. The intracellular cation concentration, membrane permeability, and compound action potential were measured and quantified. Results revealed no significant difference in the necrotic areas among different groups, and the compression model of the ex vivo spinal cord in the DSGRC had high consistency and stability. The combination therapy could attenuate cation inflow, promote cell membrane restoration, and promote the functional recovery of the spinal cord conduction after compression in ex vivo spinal cords.
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Estimulação Elétrica/métodos , Polietilenoglicóis/farmacologia , Compressão da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Animais , Terapia Combinada/métodos , Feminino , Condução Nervosa/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacosRESUMO
Spinal cord stimulation (SCS) for pain is usually implanted as an open loop system using unchanged parameters. To avoid the under and over stimulation caused by lead migration, evoked compound action potentials (ECAP) is used as feedback signal to change the stimulating parameters. This study established a simulation model of ECAP recording to investigate the relationship between ECAP component and dorsal column (DC) fiber recruitment. Finite element model of SCS and multi-compartment model of sensory fiber were coupled to calculate the single fiber action potential (SFAP) caused by single fiber in different spinal cord regions. The synthetized ECAP, superimposition of SFAP, could be considered as an index of DC fiber excitation degree, because the position of crests and amplitude of ECAP corresponds to different fiber diameters. When 10% or less DC fibers were excited, the crests corresponded to fibers with large diameters. When 20% or more DC fibers were excited, ECAP showed a slow conduction crest, which corresponded to fibers with small diameters. The amplitude of this slow conduction crest increased as the stimulating intensity increased while the amplitude of the fast conduction crest almost remained unchanged. Therefore, the simulated ECAP signal in this paper could be used to evaluate the degree of excitation of DC fibers. This SCS-ECAP model may provide theoretical basis for future clinical application of close loop SCS base on ECAP.
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Estimulação da Medula Espinal , Potenciais de Ação , Simulação por Computador , Estimulação Elétrica , Potenciais Evocados , Medula EspinalRESUMO
BACKGROUND: On the basis of some significant clinical parameters, we had an intent to establish nomograms for estimating the prognosis of patients with squamous cell carcinoma of the urinary bladder (SCCB), including overall survival (OS) and cancer-specific survival (CSS). METHODS: The data of 1210 patients diagnosed with SCCB between 2004 and 2014,were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The Cox proportional hazards regression model was applied to evaluate the association between variables and survival. Nomograms were constructed to predict the OS and CSS of an individual patient based on the Cox model. In the end, the performance of nomograms was internally validated by using calibration curves, concordance index (C-index), and k-fold cross-validation. RESULTS: Several common indicators were taken into the two nomograms (OS and CSS), including age at diagnosis, marital status, sex, TNM stage, surgical approach, tumor size, and lymph node ratio while the OS nomogram additionally contained race, grade, and chemotherapy. They had an excellent predictive accuracy on 1- and 3- year OS and CSS with C-index of 0.733 (95% confidence interval [CI], 0.717-0.749) for OS and 0.724 (95% CI, 0.707-0.741) for CSS. All calibration curves showed great consistency between actual survival and predictive survival. CONCLUSIONS: The nomograms with improved accuracy and applicability on predicting the survival outcome of patients with SCCB would provide a reliable tool to help clinicians to evaluate the risk of patients and make individual treatment strategies.
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Carcinoma de Células Escamosas/diagnóstico , Nomogramas , Neoplasias da Bexiga Urinária/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Programa de SEER/estatística & dados numéricos , Análise de Sobrevida , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Adulto JovemRESUMO
Intermittent hypoxia (IH) induced by obstructive sleep apnea (OSA) is the key factor in oxidative stress and the concomitant inflammation of endothelial cells (ECs). In recent years, the lipid sphingosine-1-phosphate (S1P) has been reported to probably play a central role in inflammatory diseases. However, its role in IH-induced endothelial injury remains uncertain. In this study, we investigated the IH-induced ECs inflammation and apoptosis, as well as the role of S1P in both. First, human umbilical vein endothelial cells (HUVECs) were treated with IH to explore the mechanism of S1P and S1P microbubbles (S1P-MBs) in HUVECs with altered function. The intracellular reactive oxygen species (ROS) significantly increased after IH treatment, which further resulted in the increased efficiency of cell apoptosis. Following the S1P and S1P-MBs treatments, the lower Bax protein and Cyt c protein levels in HUVECs indicated the protective effects of S1P for CIH-induced ECs injury. The reason may be that the enhanced expression levels of Gα(i) and S1P receptor 1 in S1P and S1P-MBs treatment groups could actively increase intracellular p-Akt and p-eNOS protein levels, which counteract the increased ROS secondary to inflammation from IH. Therefore, the Akt/eNOS signaling pathway induced by S1P may be important in protecting IH-induced ECs injury. Furthermore, the S1P-MBs may be designed as a novel S1P dosage formulation to protect the body from the ECs injuries in the future.
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Células Endoteliais da Veia Umbilical Humana/patologia , Hipóxia/patologia , Apoptose , Citocromos c/metabolismo , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Lisofosfolipídeos , Espécies Reativas de Oxigênio/metabolismo , Esfingosina/análogos & derivados , Proteína X Associada a bcl-2/metabolismoRESUMO
Bioartificial liver support system (BALSS) provides a new way to treat liver failure and leaves more time for patients who are waiting for liver transplantation. It has detoxification function as well as the human liver, at the same time it can provide nutrition and improve the internal environment inside human body. Bioreactors and hepatocytes with good biological activity are the cores of BALSS which determine the treatment effect. However, in the course of prolonged treatment, the function and activity of hepatocytes might be greatly changed which could influence the efficacy. Therefore, it is very important to detect the status of the hepatocytes in BALSS. This paper presents some common indicators of cell activity, detoxification and synthetic functions, and also introduces the commonly detection methods corresponding to each indicator. Finally, we summarize the application of detection methods of the hepatocyte status in BALSS and discuss its development trend.