RESUMO
Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with potential cardiovascular benefits, partly attributed to their bioactive metabolites. However, the underlying mechanisms responsible for these advantages are not fully understood. We previously reported that metabolites of the cytochrome P450 pathway derived from eicosapentaenoic acid (EPA) mediated the atheroprotective effect of ω-3 PUFAs. Here, we show that 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and its receptor, sphingosine-1-phosphate receptor 1 (S1PR1), in endothelial cells (ECs) can inhibit oscillatory shear stress- or tumor necrosis factor-α-induced endothelial activation in cultured human ECs. Notably, the atheroprotective effect of 17,18-EEQ and purified EPA is circumvented in male mice with endothelial S1PR1 deficiency. Mechanistically, the anti-inflammatory effect of 17,18-EEQ relies on calcium release-mediated endothelial nitric oxide synthase (eNOS) activation, which is abolished upon inhibition of S1PR1 or Gq signaling. Furthermore, 17,18-EEQ allosterically regulates the conformation of S1PR1 through a polar interaction with Lys34Nter. Finally, we show that Vascepa, a prescription drug containing highly purified and stable EPA ethyl ester, exerts its cardiovascular protective effect through the 17,18-EEQ-S1PR1 pathway in male and female mice. Collectively, our findings indicate that the anti-inflammatory effect of 17,18-EEQ involves the activation of the S1PR1-Gq-Ca2+-eNOS axis in ECs, offering a potential therapeutic target against atherosclerosis.
RESUMO
Depression is a significant factor contributing to postoperative occurrences, and patients diagnosed with depression have a higher risk for postoperative complications. Studies on cardiovascular surgery extensively addresses this concern. Several studies report that people who undergo coronary artery bypass graft surgery have a 20% chance of developing postoperative depression. A retrospective analysis of medical records spanning 21 years, involving 817 patients, revealed that approximately 40% of individuals undergoing coronary artery bypass grafting (CABG) were at risk of perioperative depression. Patients endure prolonged suffering from illness because each attempt with standard antidepressants requires several weeks to be effective. In addition, multi-drug combination adjuvants or combination medication therapy may alleviate symptoms for some individuals, but they also increase the risk of side effects. Conventional antidepressants primarily modulate the monoamine system, whereas different therapies target the serotonin, norepinephrine, and dopamine systems. Esketamine is a fast-acting antidepressant with high efficacy. Esketamine is the S-enantiomer of ketamine, a derivative of phencyclidine developed in 1956. Esketamine exerts its effect by targeting the glutaminergic system the glutaminergic system. In this paper, we discuss the current depression treatment strategies with a focus on the pharmacology and mechanism of action of esketamine. In addition, studies reporting use of esketamine to treat perioperative depressive symptoms are reviwed, and the potential future applications of the drug are presented.
Assuntos
Antidepressivos , Ketamina , Ketamina/uso terapêutico , Ketamina/administração & dosagem , Ketamina/farmacologia , Humanos , Antidepressivos/uso terapêutico , Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Animais , Período Perioperatório , Resultado do TratamentoRESUMO
Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1,2. TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications3. Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and Gi1 proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery.
Assuntos
Ácidos Aristolóquicos , Colesterol , Ácido Flufenâmico , Receptores Acoplados a Proteínas G , Paladar , Humanos , Ácidos Aristolóquicos/metabolismo , Ácidos Aristolóquicos/química , Ácidos Aristolóquicos/farmacologia , Sítios de Ligação/efeitos dos fármacos , Colesterol/química , Colesterol/metabolismo , Colesterol/farmacologia , Microscopia Crioeletrônica , Ácido Flufenâmico/química , Ácido Flufenâmico/metabolismo , Ácido Flufenâmico/farmacologia , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/química , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Ligantes , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutação , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/ultraestrutura , Paladar/efeitos dos fármacos , Paladar/fisiologia , Transducina/química , Transducina/metabolismoRESUMO
PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).
RESUMO
BACKGROUND AND PURPOSE: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic ß cells activates the CRF2 receptor (CRF2R) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis. EXPERIMENTAL APPROACH: Here, we used Arrb1-/-, Arrb2-/-, Gsfl/fl and Gqfl/fl knockout mice, the G11-shRNA-GFPfl/fl lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of Gs, G11 and ß-arrestin1 to CRF2R contributed to UCN3-induced SST secretion in pancreatic δ cells. KEY RESULTS: Our study showed that CRF2R coupled to a panel of G protein and arrestin subtypes in response to UCN3 engagement. While RyR3 phosphorylation by PKA at the S156, S2706 and S4697 sites may underlie the Gs-mediated UCN3- CRF2R axis for SST secretion, the interaction of SYT1 with ß-arrestin1 is also essential for efficient SST secretion downstream of CRF2R. The specific expression of the transcription factor Stat6 may contribute to G11 expression in pancreatic δ cells. Furthermore, we found that different UCN3 concentrations may have distinct effects on glucose homeostasis, and these effects may depend on different CRF2R downstream effectors. CONCLUSIONS AND IMPLICATIONS: Collectively, our results provide a landscape view of signalling mediated by different G protein or arrestin subtypes downstream of paracrine UCN3- CRF2R signalling in pancreatic ß-δ-cell circuits, which may facilitate the understanding of fine-tuned glucose homeostasis networks.
Assuntos
Receptores de Hormônio Liberador da Corticotropina , Transdução de Sinais , Somatostatina , Urocortinas , Animais , Masculino , Camundongos , Proteínas de Ligação ao GTP/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Somatostatina/metabolismo , Células Secretoras de Somatostatina/metabolismo , Urocortinas/metabolismoRESUMO
Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts.
Assuntos
Antígenos CD , Receptores Acoplados a Proteínas G , Transdução de Sinais , Humanos , Adesão Celular , Microscopia Crioeletrônica , Complexo Glicoproteico GPIb-IX de Plaquetas , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Antígenos CD/química , Antígenos CD/metabolismoRESUMO
BACKGROUND: For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. METHODS: In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. DISCUSSION: Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. TRIAL REGISTRATION: chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.
Assuntos
Doença da Artéria Coronariana , Inibidores da Agregação Plaquetária , Adulto , Humanos , Tirofibana/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Heparina/efeitos adversos , Resultado do Tratamento , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Endarterectomia , Fibrinolíticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Background: Tumor abnormal protein (TAP), the sugar chain protein released by tumor cells during metabolism, allows the development of a technique that exploits aggregated tumor-associated abnormal sugar chain signals in diagnosing malignancies. Clinically, we have found that TAP detection can well predict some malignancies, but several physicians have not paid attention, and related studies have been minimal. Methods: We evaluated TAP's ability to distinguish between malignancies and benign diseases by receiver operating characteristic (ROC) curve analysis and studied the possibility of monitoring malignancy progression by evaluating TAP levels in follow-up. We used Kaplan-Meier survival curves and Cox proportional hazard regression models to investigate the relationship between TAP and prognosis. Results: TAP levels were higher in whole solid malignancies and every type of solid malignancy than in benign patients. ROC curve analysis showed that TAP levels aid in distinguishing between malignancies and benign diseases. TAP levels decreased in patients with complete remission (CR) after treatment and increased in patients with relapse from CR. Patients with metastases had higher TAP levels than non-CR patients without metastases. There was no difference in overall survival among patients with different TAP levels, and multivariate analysis suggested that TAP was not an independent risk factor for solid malignancies. Conclusion: TAP is an effective screening biomarker for many solid malignancies that can be used to monitor the progression of malignancies but not to prognosticate.
RESUMO
Background: The benefits of selective coronary vein bypass grafting (SCVBG) for patients with severe diffuse lesions of the right coronary artery (RCA) who are unsuitable for coronary endarterectomy (CE) are unclear. Methods: We recruited patients with diffuse lesions of the RCA undergoing coronary artery bypass surgery between January 2015 and December 2018 and matched SCVBG and CE patients on propensity score (PS). We evaluated the degree of single-stenosis in the RCA, incidence of perioperative myocardial infarction (MI) and major adverse cardiovascular and cerebrovascular events (MACCE), influencing factors of perioperative MACCE, long-term survival rate, and long-term MACCE incidence. Results: Overall, 430 patients were enrolled: 344 (80%) underwent CE and 86 (20%) underwent SCVBG (n=78 and n=64, respectively, after PS matching). The incidence of perioperative MI and MACCE were significantly lower in the SCVBG group (5.1% vs. 1.5%, P<0.05; and 10.2% vs. 4.7%, P<0.05). When the vascular flow rate of the graft anastomosed to RCA in the SCVBG group was above 100 mL/min, the incidence of perioperative MACCE significantly increased [odds ratio (OR): 1.94, 95% confidence interval (CI): 1.42-2.03]. Choosing the bilateral internal mammary artery for SCVBG reduced the incidence of perioperative MACCE (OR: 0.82, 95% CI: 0.68-0.92). There was no significant difference in the rates of long-term survival or MACCE between the two groups before or after PS matching (P>0.05). Conclusions: SCVBG is an acceptable surgical intervention for patients with severe diffuse RCA lesions.
RESUMO
Chronic inflammation due to islet-residing macrophages plays key roles in the development of type 2 diabetes mellitus. By systematically profiling intra-islet lipid-transmembrane receptor signalling in islet-resident macrophages, we identified endogenous 9(S)-hydroxy-10,12-octadecadienoic acid-G-protein-coupled receptor 132 (GPR132)-Gi signalling as a significant contributor to islet macrophage reprogramming and found that GPR132 deficiency in macrophages reversed metabolic disorders in mice fed a high-fat diet. The cryo-electron microscopy structures of GPR132 bound with two endogenous agonists, N-palmitoylglycine and 9(S)-hydroxy-10,12-octadecadienoic acid, enabled us to rationally design both GPR132 agonists and antagonists with high potency and selectivity through stepwise translational approaches. We ultimately identified a selective GPR132 antagonist, NOX-6-18, that modulates macrophage reprogramming within pancreatic islets, decreases weight gain and enhances glucose metabolism in mice fed a high-fat diet. Our study not only illustrates that intra-islet lipid signalling contributes to islet macrophage reprogramming but also provides a broadly applicable strategy for the identification of important G-protein-coupled receptor targets in pathophysiological processes, followed by the rational design of therapeutic leads for refractory diseases such as diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Ilhotas Pancreáticas , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Microscopia Crioeletrônica , Ilhotas Pancreáticas/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: We visually assessed the research hotspots of familial hypercholesterolemia (FH) using bibliometrics and knowledge mapping in light of the research state and development trend of FH. METHODS: We employed bibliometric tools, such as CiteSpace and the alluvial generator, to illustrate the scientific accomplishments on FH by extracting pertinent literature on FH from the Web of Science Core Collection database from January 1, 2002, to December 31, 2022. RESULTS: A total of 4402 papers in total were selected for study; 29.2% of all articles globally were from the USA, followed by the Netherlands and England. The University of Amsterdam, University of Oslo, and University of Western Australia are the 3 institutions with the most publications in this area. Gerald F. Watts, Raul D. Santos, and John J. P. Kastelein wrote the majority of the pieces that were published. The New England Journal of Medicine, Circulation, and Atherosclerosis were the journals with the greatest number of papers in this field. Prevalence and genetic analysis of FH, proprotein convertase subtilisin/kexin 9 inhibitors, and inclisiran are current research hotspots for the condition. Future research in this area will be focused on gene therapy. CONCLUSIONS: FH research has shown shows a trend of ascending followed by leveling off. The prevalence and diagnosis of FH, proprotein convertase subtilisin/kexin 9 inhibitors, inclisiran, and gene therapy are current research hotspots. This report may serve as a reference for current research trends.
Assuntos
Aterosclerose , Hiperlipoproteinemia Tipo II , Humanos , Austrália , Bibliometria , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/terapia , Pró-Proteína ConvertasesRESUMO
Background and aims: The risk factors of perioperative and long-term cardiovascular events in patients undergoing coronary artery bypass grafting (CABG) with adjunctive coronary endarterectomy (CE) are not well determined. This study evaluated the clinical value of coronary plaque burden, coronary anatomic stenosis, and serum biomarkers for predicting perioperative cardiovascular events after off-pump CABG + CE. Methods: This retrospective cohort single-center study enrolled 125 patients undergoing off-pump CABG + CE between February 2018 and September 2021 in China. Coronary plaque burden was reflected by the length of plaque removed by CE. Plaque length-max, which represents the plaque length in patients undergoing single-vessel CE and the maximum plaque length in patients undergoing multivessel CE, was calculated. The primary endpoint was perioperative myocardial infraction (PMI). Results: Plaque length-max was significantly higher in patients with PMI than in those without PMI (2.4 ± 1.5 vs. 1.6 ± 0.9, p = .001). A threshold plaque length-max of 1.15â cm was an independent predictor of PMI (area under the curve: 0.67; sensitivity 87.9%; specificity 59.8%; p = .005). Patients with plaque length-max ≥1.15 had a > 5-fold increase in PMI after adjusting for confounding factors (odds ratio = 5.89; p = .002). Furthermore, interleukin-6 (Beta = .32: p = .028), CD68 (Beta = .34; p = .045), and osteopontin (Beta = .43; p = .008) were significantly correlated with plaque length-max. Conclusions: Plaque length-max was superior to clinical cardiovascular risk factors in predicting PMI occurrence after off-pump CABG + CE, which might be associated with systemic and plaque inflammation state.
RESUMO
OBJECTIVE: To verify the administration of a new nano delivery system coated with Tirofiban on preventing early thrombosis in vein graft. METHODS: Forty New Zealand white rabbits were randomly divided into five groups with eight rabbits in each group. The rabbits of all groups underwent jugular vein transplantation, except group I with only neck opening and closing operation. Vein grafts of group II were preprocessed by intravenous injection of normal saline; group III were preprocessed by tirofiban alone; group IV were preprocessed by unloaded nanoparticles of PLGA-PEG; group V were preprocessed by PLGA-PEG coated with tirofiban. Coagulation and platelet function of peripheral and vein graft blood were detected at 1, 2, 4, 12 h and 1, 3, 7, 10, 14 days after operation. Patency rate of vein graft and blood flow index were measured by vascular ultrasound at third, seventh, 10th, and 14th days after operation; two rabbits in each group were randomly sacrificed at the corresponding time of detection. Pathological differences of vein grafts were observed by HE stainin. RESULTS: The patency rate of vein grafts in group V was significantly higher than that in group II to IV. The platelet and platelet aggregation rate in group V were inhibited in vein graft blood significantly. The post-operative PT and APTT in vein graft blood in group V were increased obviously while the FBG, D-dimer and FDP were significantly inhibited. Except group I, the lumen loss rate of vein grafts in group V was significantly lower than that in other groups, and vein graft blood in group V had a significant lower expression of platelet P-selectin and GP IIb/IIIa receptor than that in other groups. CONCLUSION: This study proves that PEG-PLGA coated with tirofiban can effectively prevent early vein graft stenosis from thrombosis by inhibition of platelet function, coagulation function.
RESUMO
Continuous and efficient energy capture represents a long-sought dream of mankind. The brain is a major energy-consuming organ; an adult brain accounts for about 2% of the body weight but consumes about 20% of the body's energy. However, it is still unclear how the brain achieves efficient use of energy. Here, using nerve cells as test subjects, we found that THz photons with a specific frequency can effectively restore the reduced frequency of action potentials caused by inadequate ATP supply, which has been demonstrated as a novel mode of energy supply, present photons emission at a particular frequency from the breaking of the ATP phosphate bond. This energy supply mechanism may play a key biophysical basis for explaining how the body efficiently obtains energy, because the quantized chemical reactions could have a high energy efficiency and ultrahigh selectivity compared with the traditional thermochemistry and photochemistry.
RESUMO
The sixth generation (6G) communication will use the terahertz (THz) frequency band, which requires flexible regulation of THz waves. For the conventional metallic metasurface, its electromagnetic properties are hard to be changed once after being fabricated. To enrich the modulation of THz waves, we report an all-optically controlled reconfigurable electromagnetically induced transparency (EIT) effect in the hybrid metasurface integrated with a 10-nm thick MoTe2 film. The experimental results demonstrate that under the excitation of the 800 nm femtosecond laser pulse with pump fluence of 3200 µJ/cm2, the modulation depth of THz transmission amplitude at the EIT window can reach 77%. Moreover, a group delay variation up to 4.6 ps is observed to indicate an actively tunable slow light behavior. The suppression and recovery of the EIT resonance can be accomplished within sub-nanoseconds, enabling an ultrafast THz photo-switching and providing a promising candidate for the on-chip devices of the upcoming 6G communication.
RESUMO
BACKGROUND: 18F-sodium fluoride (18F-NaF) positron emission tomography (PET)/computed tomography (CT) is a promising new approach for assessing microcalcification in vascular plaque. OBJECTIVES: This prospective study aimed to evaluate the associations between in vivo coronary 18F-NaF PET/CT activity and ex vivo histological characteristics, to determine whether coronary 18F-NaF activity is a novel biomarker of plaque pathological vulnerability, and to explore the underlying physiological environment of 18F-NaF adsorption to vascular microcalcification. METHODS: Patients with coronary artery disease (CAD) underwent coronary computed tomography angiography (CTA) and 18F-NaF PET/CT. Histological vulnerability and immunohistochemical characteristics were evaluated in coronary endarterectomy (CE) specimens from patients who underwent coronary artery bypass grafting with adjunctive CE. Correlations between in-vivo coronary 18F-NaF activity with coronary CTA adverse plaque features and with ex vivo CE specimen morphological features, CD68 expression, inflammatory cytokines expression (tumor necrosis factor-α, interleukin-1ß), osteogenic differentiation cytokines expression (osteopontin, runt-related transcription factor 2, osteocalcin) were evaluated. High- and low- to medium-risk plaques were defined by standard pathological classification. RESULTS: A total of 55 specimens were obtained from 42 CAD patients. Coronary 18F-NaF activity of high-risk specimens was significantly higher than low- to medium-risk specimens (median [25th-75th percentile]: 1.88 [1.41-2.54] vs 1.12 [0.91-1.54]; P < 0.001). Coronary 18F-NaF activity showed high discriminatory accuracy in identifying high-risk plaque (AUC: 0.80). Coronary CTA adverse plaque features (positive remodeling, low-attenuation plaque, remodeling index), histologically vulnerable features (large necrotic core, thin-fibro cap, microcalcification), CD68 expression, tumor necrosis factor-α expression, and interleukin-1ß expression correlated with coronary 18F-NaF activity (all P < 0.05). No significant association between coronary 18F-NaF activity and osteogenic differentiation cytokines was found (all P > 0.05). CONCLUSIONS: Coronary 18F-NaF activity was associated with histological vulnerability, CD68 expression, inflammatory cytokines expression, but not with osteogenic differentiation cytokines expression. 18F-NaF PET/CT imaging may provide a powerful tool for detecting high-risk coronary plaque and could improve the risk stratification of CAD patients.
Assuntos
Calcinose , Doença da Artéria Coronariana , Placa Aterosclerótica , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluoreto de Sódio , Interleucina-1beta , Estudos Prospectivos , Osteogênese , Fator de Necrose Tumoral alfa , Compostos Radiofarmacêuticos/metabolismo , Fatores de Risco , Valor Preditivo dos Testes , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons/métodosRESUMO
PURPOSE: To investigate the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients undergoing off-pump coronary artery bypass grafting (OPCABG) and analyze the effects of OSAHS on the incidence of post-OPCABG complications, length of stay in intensive care unit (ICU) and hospitalization, and hospital expense. MATERIALS AND METHODS: This prospective study included patients undergoing OPCABG at Beijing An Zhen hospital from January 2018 to December 2018. OSAHS was diagnosed by using a portable sleep monitor before surgery. RESULTS: Among 74 patients, the prevalence of OSAHS and moderate to severe OSAHS (apnea hypopnea index (AHI) ≥ 15) was 70% and 53%, respectively. Compared with the no to mild OSAHS group (AHI < 15), the moderate to severe OSAHS group presented a lower ejection fraction (P = 0.013). Between these two groups, the incidence of post-OPCABG complications; the duration of intubation, ICU stay, and hospitalization; and the hospital expense did not differ. Notably, the ejection fraction was significantly negatively correlated with the duration of ICU stay and hospital expense. CONCLUSIONS: Patients undergoing OPCABG with severe OSAHS are likely to exhibit a low ejection fraction and poor heart function, which may require a longer ICU stay and incur higher hospital expenses.
Assuntos
Apneia Obstrutiva do Sono , Humanos , Polissonografia , Estudos Prospectivos , Apneia Obstrutiva do Sono/diagnóstico , Complicações Pós-Operatórias/etiologia , Síndrome , Ponte de Artéria CoronáriaRESUMO
Background: This study sought to compare and evaluate the clinical efficacy and safety of Y-type coronary artery bypass grafting (CABG) and sequential CABG. However, the prognosis and complication rate of the two treatments are different. Therefore, we need to systematically compare the efficacy and safety of the two surgical schemes. Methods: A total of 112 patients who underwent Y-type CABG and 113 patients who underwent sequential CABG were selected from January 2020 to December 2020. The patients undergoing Y-type CABG of the great saphenous vein (SV) were classified as the experimental group, and those undergoing sequential anastomosis were classified as the control group. The intraoperative blood flow at each anastomotic site of the venous sequential CABG, left ventricular ejection fraction (LVEF), and left ventricular diastolic diameter (LVEDD) at the end of 3 months, 6 months, and 1 year after surgery, the incidence rate of major adverse cardiovascular events, and coronary angiography (CAG) after readmissions due to similar symptoms were compared between the 2 groups. The bridging vascular blockage rate was also determined. Results: There was no significant difference in cardiac function between the 2 groups in the short term, and the incidence of major adverse cardiovascular events in the 2 groups mainly occurred in the middle-postoperative period (1 year after surgery) or later. There was no statistical difference in the intraoperative real-time blood flow measurements at each anastomosis of the venous bridge between the 2 groups. Compared to the control group, the LVEF of the experimental group was significantly increased at the 1-year follow-up point (51.6±5.1 vs. 67.6±5.6, P=0.001). During the operation of Y-type coronary artery bypass grafting, the incidence of major adverse cardiovascular events, vascular bridge, and anastomotic blockage were significantly decreased (16 vs. 39, P=0.023). Conclusions: Large SV Y-type CABG can improve postoperative left heart function and reduce the incidence of postoperative adverse events, which may be of great significance for improving the postoperative mid-term survival rate of patients.
RESUMO
BACKGROUND: 18F-NaF PET/CT is a novel approach to detect and quantify microcalcification in atherosclerosis. We aimed to explore the underlying systematic vascular osteogenesis in the coronary artery and aorta in patients with multivessel coronary artery disease (CAD). METHODS: Patients with multivessel CAD prospectively underwent 18F-NaF PET/CT. The coronary microcalcification activity (CMA) and aortic microcalcification activity (AMA) were calculated based on both the volume and intensity of 18F-NaF PET activity. Peri-coronary adipose tissue (PCAT) density was measured in adipose tissue surrounding the coronary arteries and the 18F-NaF tissue-to-blood ratio (TBR) was measured in the coronary arteries. RESULTS: 100 patients with multivessel CAD were prospectively recruited. The CMA was significantly associated with the AMA (r = 0.70; P < .001). After multivariable adjustment, the CMA was associated with the AMA (Beta = 0.445 per SD increase; P < .001). The coronary TBR was also significantly associated with the PCAT density (r = 0.56; P < .001). The PCAT density was independently associated with the coronary TBR after adjusting confounding factors. CONCLUSIONS: Coronary 18F-NaF uptake was significantly associated with the PCAT density. There was a significant relationship between the coronary and the aortic 18F-NaF uptake. It might indicate an underlying systematic vascular osteogenesis in patients with multivessel CAD.
Assuntos
Aterosclerose , Calcinose , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluoreto de Sódio , Aterosclerose/diagnóstico por imagem , Aorta , Radioisótopos de FlúorRESUMO
A discrimination-experiment method is developed to investigate the transient heat transfer of air jet impingement by discretizing the solid domain into mutually adiabatic test cylinders. This method can not only reduce the influence of the transverse heat transfer of a solid domain on the heat transfer characteristics of the jet but can also simplify the two-dimensional or three-dimensional heat conduction problem into a one-dimensional problem. Moreover, the discrimination-experiment method eliminates the embedment of thermocouples into the solid domains, further improving the accuracy and reliability of the proposed method. The transient heat transfer characteristics of a supersonic air jet impinging on a high-temperature target (860°C) and the effects of thermo physical parameters, such as the density, specific heat capacity, thermal conductivity and nozzle-to-target distance (H/D = 3, 4, and 5) are analyzed in detail using the discrimination-experiment method. The results provide important guidance for the thermal design of supersonic air jet impingement.