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An increasing number of experimental and clinical observation suggest that the use of anaesthetics is closely associated with postoperative central nervous system (CNS) complications, such as delirium and cognitive dysfunction. Brain energy rescue is an emerging therapeutic strategy for central nervous system disease (CNSDs). However, the effect of anaesthetics on nerve cell energy utilisation, especially microglia, and its potential effects on cell function still unclear. Elucidating the effects of anaesthetics on lipid droplets, which are specific lipid storage organs, and phagocytosis of microglia is crucial to discover a new therapeutic concept for postoperative CNS complications. Here, we studied the effects of the commonly used anaesthetic midazolam on lipid droplets and phagocytosis in immortalised microglial BV2 cells. Lipid droplets were assessed by flow cytometry and triglyceride quantification. The phagocytosis of BV2 cells was evaluated by detecting their phagocytosis by latex beads. Additionally, the autophagy of BV2 cells was evaluated by western blot and observation under microscopy. Our results showed that midazolam caused lipid droplet accumulation and reduced phagocytosis in BV2 cells, and inhibition of lipid droplet accumulation partially restored phagocytosis. Furthermore, midazolam blocks autophagic degradation by increasing phosphorylated TFEB in BV2 cells, inhibition of midazolam-increased phosphorylated TFEB might contribute to the improvement of autophagic flux by rapamycin. Moreover, promoting autophagy reverse the lipid droplet accumulation and phagocytosis decrease. This study suggests autophagy is a target for attenuating lipid droplet accumulation, normal degradation of lipid droplets is important for maintaining microglia phagocytosis and attenuating the side effects of midazolam on the CNS.
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Gotículas Lipídicas , Midazolam , Midazolam/farmacologia , Fagocitose , Autofagia , Microglia/metabolismoRESUMO
PURPOSE: Vitamin D insufficiency and obesity are recognized as worldwide concerns and have been linked with each other. New anthropometric indices reflect visceral obesity better than traditional anthropometric indices. Our aim was to identify the specific correlations of novel and traditional anthropometric indices with 25-hydroxyvitamin D (25(OH)D) concentrations by sex and age. METHODS: Cross-sectional data on sociodemographic characteristics, lifestyle factors, clinical characteristics and biochemical measurements were collected for 12,617 Chinese adults. Four traditional anthropometric indices, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), and two novel anthropometric indices, body roundness index (BRI) and body shape index (ABSI), were calculated. RESULTS: In both sexes, the mean values of BMI, WC, WHtR and BRI tended to increase with 25(OH)D insufficiency, regardless of adjustment (all P < 0.05). Males with insufficient 25(OH)D had increased odds of obesity (assessed by BMI, WC, WHtR, BRI and ABSI) compared to the odds of males with sufficient 25(OH)D. Females with insufficient 25(OH)D had a higher chance of general obesity (assessed by BMI). Low 25(OH)D status was associated with indicators of obesity only in participants aged 45-64 years in both sexes. CONCLUSION: A inverse association between obesity and lower vitamin D levels was found. Moreover, in addition to BMI, novel indicators of visceral adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations in males. The effects of optimizing vitamin D levels in obese Chinese adults need further examination, particularly in middle-aged males. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.
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Vitamina D , Adulto , Antropometria , Índice de Massa Corporal , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
BACKGROUND: This study aimed to investigate the effect of the Phellinus linteus (Mesima) decoction on podocyte injury in a rat model of focal and segmental glomerulosclerosis (FSGS) and evaluate the potential mechanisms. METHODS: FSGS resembling primary FSGS in humans was established in rats by uninephrectomy and the repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, low-dose group of P. linteus decoction (PLD-LD), medium-dose group of P. linteus decoction (PLD-MD), and high-dose group of P. linteus decoction (PLD-HD). Blood and urine analysis were performed after 12 weeks and the molecular indicators of renal function and the renal pathological changes were examined. RESULTS: FSGS developed within 12 weeks in the test group and showed progressive proteinuria and segmental glomerular scarring. Urinary protein, serum creatinine, urea nitrogen, triglycerides and cholesterol were significantly reduced following the 12-week intervention with P.linteus decoction, especially in the PLD-LD group. Renal nephrin and podocin were markedly increased. Moreover, the pathological damage in the renal tissue was alleviated by the PLD-LD intervention. CONCLUSION: The P. linteus decoction alleviated the podocyte injury in the FSGS rat model, thus minimizing the progression of glomerular sclerosis and improving renal function.
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Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Podócitos/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Masculino , Proteínas de Membrana/metabolismo , Phellinus , Podócitos/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the most common glomerular etiology of end-stage kidney disease (ESKD). Increasing evidence has indicated the reparative potential of mesenchymal stem cells (MSCs) in damaged diseased kidneys. However, the effect of bone marrow mesenchymal stem cells (BMSCs) on the FSGS progression remains unclear. This study aimed to investigate the protective effects of BMSCs on FSGS progression. METHODS: A rat model of FSGS was generated via unilateral nephrectomy plus adriamycin injection. Rat BMSCs were isolated and characterized on the basis of their differentiative potential towards adipocytes and osteoblasts and via flow cytometry analysis. Thereafter, rat BMSCs were transplanted into FSGS recipients through the caudal vein. After 8 weeks, 24-h proteinuria, serum creatinine, and urea nitrogen levels were determined. Renal morphology was assessed using a light and transmission electron microscope. MMP9 and TIMP-1 positive cells were detected via immunohistochemical analysis. Expression levels of proinflammatory cytokines IL-6 and TNF-α were examined via RT-PCR. RESULTS: The isolated adherent cells from the bone marrow of rats were phenotypically and functionally equivalent to typical MSCs. Clinical examination revealed that BMSC transplantation reduced the 24-h urinary protein excretion, and serum creatinine and urea nitrogen levels. Renal morphology was ameliorated in BMSCs-transplanted rats. Mechanistically, BMSC transplantation significantly downregulated TIMP-1 and upregulated MMP9, thereby increasing the renal MMP9/TIMP-1 ratio. Moreover, BMSC transplantation also downregulated IL-6 and TNF-α. CONCLUSIONS: BMSC transplantation can attenuate FSGS progression in a rat model of FSGS, thereby providing a theoretical foundation for the application of autologous BMSCs in clinical FSGS therapy.
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Modelos Animais de Doenças , Progressão da Doença , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Doxorrubicina/efeitos adversos , Glomerulosclerose Segmentar e Focal/etiologia , Masculino , Células-Tronco Mesenquimais/fisiologia , Nefrectomia/efeitos adversos , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVES: This study aims to determine the effectiveness of a messaging app (WeChat) in improving patients' compliance and reducing the duration of orthodontic treatment (DOT). MATERIALS AND METHODS: A randomized controlled trial was performed in a dental hospital and a clinic from August 2012 to May 2015. Orthodontic patients were included at the beginning of treatment. Patients with multiphase treatment or braceless technique were excluded. Participants were randomized to WeChat group (received regular reminders and educational messages) or control group (received conventional management) and were followed up until the treatment was completed. Primary outcome measure was DOT. Others were late and failed attendance, bracket bond failure, and oral hygiene condition. RESULTS: One hundred twelve patients in each group participated and completed the trial. DOT in WeChat group were 7.3 weeks shorter (P = 0.007). There were less failed attendance (3.1 vs. 10.9 %, P < 0.001), late attendance (20.1 vs. 29.9 %, P < 0.001), and bracket bond failure (11.8 vs. 16.1 %, P < 0.001) in WeChat group than control. There was no difference in orthodontic plaque index nor modified gingivitis index between the two groups before and after treatment. Number of failed attendances was identified as an independent factor affecting DOT (P = 0.004; HR = 0.89, 95 % CI 0.84 to 0.95). CONCLUSIONS: The intervention with WeChat is effective in reducing the treatment duration and bracket bond failure, and improving the attendance in orthodontic patients. CLINICAL RELEVANCE: DOT can be reduced by improving patient's compliance. The messaging app is useful for outpatient education and management.
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Aplicativos Móveis , Ortodontia Corretiva , Cooperação do Paciente , Adolescente , Adulto , China , Feminino , Humanos , Masculino , Fatores de TempoRESUMO
Modern industrial application and technologies require materials with superior mechanical and thermal properties. Kevlar fibers have been known as fibrous materials with good properties of high strength and high decomposition temperature which have become a hot research field in recent years. The properties of fibrous materials depend on their structures and compositions. Thermal decomposition processing of the materials is of great significance for their structures and thermal properties. As a new technique, thermogravimetric (TG) analysis coupled with Fourier transform infrared spectroscopy(FTIR), are able to analyze materials not only qualitatively but also quantitatively. This method has obvious advantages in researching the thermal decomposition of many materials. However, the thermal decomposition processing of Kevlar fibers is rarely reported in the literature, therefore, we firstly studied the pyrolysis behavior of Kevlar fibers with thermogravimetric analysis coupled with Fourier transform infrared spectroscopy at the temperature of 30~800 â. We not only obtained the processing of the Kevlar fibers' thermal decomposition with great details but also the products of every stage. Experimental results exhibited that the decomposition of Kevlar fibers has experienced three stagesï¼ 100~240, 240~420 and 420~800 â. The weight loss of Kevlar fibers was quite slow before 500 â. The third stage was the main stage of the decomposition, and the amount of residue finally reached to a mass percent of 56.21%. FTIR analysis illustrated that free water released from Kevlar fibers at the first stage, followed by the dehydration and depolymerization which made polymer chains short. Finally the fiber fragments further reacted and produced the gases of small molecular mass, and the main products were water, ammonia, carbon monoxide and carbon dioxide. Generation rate of water was increased; the emission of ammonia was at the same rate; carbon monoxide was only produced at the temperature of 515~630 â, then turned into carbon dioxide. The release of carbon dioxide was on rise because of the conversion process of carbon monoxide, and then dropped to a certain value.
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OBJECTIVE: C4 deficiency is the most commonly inherited immune disorder in human. The present study investigated the characteristics of the IgAN patients with low serum C4 levels. METHODS: We performed a prospective observational study. Clinical as well as histopathologic parameters were assessed. A Kaplan-Meier survival analysis was performed concerning the primary outcome defined as the serum creatinine increased 1.5-fold from baseline. The prognostic significances of clinical and histopathologic parameters were determined using Cox proportional hazards models. RESULTS: Five-hundred twelve biopsy proven IgAN cases were available for analysis with a median follow-up of 38.4 months. Ninety-nine cases (19.34%) presented with low C4 levels (LowC4 group) and the other 413 cases did not (NlowC4 group). At the time of renal biopsy, renal injury was lighter in the LowC4 group compared with the NlowC4 group. Renal C4 deposition was significantly decreased while IgM deposition was increased in the LowC4 group. A correlation analysis shows that lower C4 levels were associated with better renal presentations at biopsy. However, the risk of developing the primary outcome was significantly greater in those with low C4 levels. Specifically, during the follow-up period, the risk of developing primary outcome was nearly ten folds higher in those with low C4, compared to those without low C4. CONCLUSION: There is a high prevalence of low C4 levels in IgAN patients. These patients with low C4 levels exhibited better renal presentations at the time of renal biopsy, whereas might be associated with a poor prognosis.
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Complemento C4 , Glomerulonefrite por IGA , Glomérulos Renais/patologia , Adulto , Austrália/epidemiologia , Biópsia , Complemento C4/análise , Complemento C4/deficiência , Lectina de Ligação a Manose da Via do Complemento/imunologia , Creatinina/sangue , Feminino , Glomerulonefrite por IGA/epidemiologia , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Testes de Função Renal/métodos , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
The majority of cardiovascular events in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (PPCI) arise from the progression of nonculprit lesions (NCL) during the long-term follow-up period. However, the clinical and angiographic factors related to the progression of nonculprit lesions are unknown.The purpose of the study was to investigate the clinical and angiographic factors related to the progression of nonculprit lesions of patients with STEMI undergoing PPCI.A total of 492 patients with STEMI who underwent PPCI from January 2006 to December 2009 were enrolled. All patients underwent PPCI as a treatment for the culprit lesion. The clinical and angiographic follow-up was performed at 12 months. Primary endpoint: Clinically driven nonculprit lesion PCI. The levels of serum catecholamines [epinephrine (E), norepinephrine (NE)] and C-reactive protein (CRP) were assayed, and the clinical and angiographic features were also analyzed.The clinical and angiographic follow-up was performed in 492 patients, and 45 patients underwent clinically driven nonculprit lesions PCI (study group). A total of 447 patients were free of additional PCI (control group). There were significant differences in the level of catecholamines (E (621.48 ± 79.31) pg/mL versus (268.14 ± 73.26) pg/mL, P < 0.0001), NE (6212.43 ± 822.41) pg/mL versus (3218.34 ± 614.16) pg/mL, P < 0.0001), CRP (3.29 ± 1.31) mg/dL versus (2.51 ± 1.14) mg/dL, P < 0.0001, cTnI peak value (27.27 ± 4.02) ng/mL versus (16.12 ± 3.23) ng/mL, P < 0.0001), thrombotic lesion rate ((62.22% versus 23.04%), P < 0.0001), ≥ 2 vessel lesions rate (80.00% versus 46.09%), P < 0.0001), culprit lesion length ((33.2 ± 2.9 versus 28.1 ± 3.1), P = 0.013), and complex lesion rate ((57.78% versus 36.02%), P = 0.006) between the two groups. Correlation analysis between nonculprit lesion stenosis degree and serum E, serum NE, serum CRP, cTnI peak value, thrombotic lesion rate, ≥ 2 vessel lesions rate, culprit lesion length, and complex lesion rate showed that there were significant correlations between serum E, serum NE, serum CRP, cTnI peak value, thrombotic lesion rate, ≥ 2 vessel lesions rate, culprit lesion length, complex lesion rate, and nonculprit lesion stenosis degree. The correlation coefficients were 0.95, 0.97, 0.83, 0.90, 0.81, 0.84, 0.95, and 0.96, respectively, and P < 0.0001, P < 0.0001, P = 0.01, P = 0.01, P = 0.01, P = 0.01, P < 0.0001, and P < 0.0001, respectively.Recurrent PCI was mainly due to nonculprit lesion progression in patients with STEMI after primary PCI. Complex nonculprit lesions may be prone to for additional PCI. Chronic inflammation and sustained stress may be involved in the progression of nonculprit lesions in patients with STEMI.
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Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Recidiva , Reoperação/estatística & dados numéricosRESUMO
The deliberate pork adulteration with lymph nodes is a common adulteration phenomenon, and it poses a serious threat to public health and food safety. An untargeted metabolomics and lipidomics approach based on ultrahigh performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap high resolution mass spectrometry (MS) was used to distinguish lymph nodes from minced pork. The principal component analysis and orthogonal projection to latent structures discriminant analysis models were established with the good of fitness and predictivity. The results showed that there were significant differences in metabolites and lipids between lymph nodes and pork. A total of 16 significantly differentiated metabolites were identified, of which 1-palmitoylglycerophosphocholine, 12,13-dihydroxy-9-octadecenoic acid, and prostaglandin E2 (PGE2) were positively correlated with lymph node content and were identified as potential markers of lymph nodes. These three markers were combined to create a binary logistic regression model, and a combined-factor exceeding 0.75 was ultimately identified as a marker for pork adulteration with lymph nodes. The desorption electrospray ionization-MS images showed that PGE2 had a higher relative abundance in the lymph node region than in adjacent non-lymph node regions, indicating that PGE2 was a marker that contributed significantly for identifying lymph nodes adulteration into pork. Our results provide a theoretical basis for identifying lymph node adulteration, which will contribute to combating fraud in the meat industry.
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Carne de Porco , Carne Vermelha , Animais , Suínos , Cromatografia Líquida de Alta Pressão/métodos , Lipidômica , Cromatografia Líquida/métodos , Metabolômica/métodosRESUMO
Nano-TiO2 is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO2 on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO2 at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO2 on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO2 caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1ß and TNF-α in rat thyroid tissue. Nano-TiO2 also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO2 reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO2 damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO2 could be a potential risk factor for thyroid dysfunction.
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OBJECTIVE: The 'no-reflow' phenomenon after a primary percutaneous coronary intervention (pPCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) is a strong predictor of both short- and long-term mortality. We therefore developed and prospectively validated a risk score system in order to identify STEMI patients at high risk in terms of no-reflow after primary PCI. METHODS: The first part of our study used data from 1,615 STEMI patients who underwent primary PCI within 12 h from symptom onset. Using logistic regression, we derived a risk score to predict angiographic no-reflow using baseline clinical variables. From this score, we developed a simplified fast-track screen that can be used before reperfusion. In the second part of our study, we prospectively validated the score system using receiver-operating characteristic (ROC) curves with data from 692 STEMI patients. RESULTS: The model included six clinical items: age, neutrophil count, admission plasma glucose, ß-blocker treatment, time-to-hospital admission and Killip classes. The risk score system demonstrated a good risk prediction with a c-statistic of 0.757 (95% CI 0.732-0.781) based on ROC analysis. CONCLUSION: A simple risk score system based on clinical variables is useful to predict the risk of developing no-reflow after pPCI in patients with STEMI.
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Infarto do Miocárdio/terapia , Fenômeno de não Refluxo/diagnóstico , Intervenção Coronária Percutânea , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/métodos , Estudos Prospectivos , Curva ROC , Medição de RiscoRESUMO
OBJECTIVE: To explore the effect of resveratrol on transforming growth factor-beta1 (TGF-beta1) induced transdifferentiation of podocytes. METHODS: Mouse podocytes in vitro cultured under differentiating conditions for 10 days were divided into the normal group, the model group, the high dose resveratrol group, and the low dose resveratrol group. The podocytes in the high and low dose resveratrol groups were intervened with 5 micromol/L and 2 micromol/L resveratrol respectively for 30 min. Those in the model group and the two resveratrol treated groups were continually incubated with 5 ng/mL TGF-beta1 for 72 h. Those in the normal group were routinely cultured. The protein expression of podocyte phenotypic protein molecules such as E-cadherin, P-cadherin, zonula occludens-1 (ZO-1), NEPH1, and alpha-smooth muscle-actin (alpha-SMA) were detected by immunocytochemistry, flow cytometry (FCM), and Western blot. A simple albumin influx assay was used to evaluate the filtration barrier function of podocyte monolayer. RESULTS: Compared with the normal control group, E-cadherin (+) percentage rate, the protein expression of P-cadherin, ZO-1, and NEPH1 significantly decreased in the model group (P < 0.05), but the expression of alpha-SMA and albumin permeability across podocyte monolayers increased significantly (P < 0.05). Compared with the model group, E-cadherin (+) percentage rate significantly increased (P < 0.05) and albumin permeability across podocyte monolayers decreased significantly (P < 0.05) in the high and low dose resveratrol groups. In the low dose resveratrol group, the expression of P-cadherin and NEPH1 significantly increased (P < 0.05). In the high dose resveratrol group, the expression of P-cadherin, ZO-1, and NEPH1 increased significantly, and the expression of alpha-SMA decreased significantly (P < 0.05). The correlations between resveratrol concentrations and the expression of E-cadherin (+), P-cadherin, and NEPH1 were significantly positive (r(E-cadherin (+)) = 0.772, r(P-cadherin) = 0.756, r(NEPH1) = 0.809, P < 0.05). CONCLUSION: The role of resveratrol in inhibiting TGF-beta1 induced phenotype abnormality might be an important mechanism for preserving the integrality of glomerular filtration barrier and decreasing proteinuria.
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Transdiferenciação Celular/efeitos dos fármacos , Podócitos/citologia , Podócitos/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Células Cultivadas , Túbulos Renais/citologia , Túbulos Renais/efeitos dos fármacos , Camundongos , Resveratrol , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Papillary thyroid carcinoma is the most common thyroid malignant tumor and usually has a fine prognosis. The most common metastatic site is the cervical lymph node, and distant metastasis is rare. This report describes a female patient with papillary thyroid carcinoma who presented with multiple metastases in the cervical lymph nodes, breast, and spine. The patient's disease course lasted 11 years, and eventually metastatic cancer led to the patient's death. We also analyzed the survival rate and median survival time of papillary thyroid carcinoma with multiple organ metastases using data in the literature.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Feminino , Câncer Papilífero da Tireoide/patologia , Carcinoma Papilar/patologia , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/patologia , Linfonodos/patologiaRESUMO
PURPOSE: To investigate the effects of α2A-adrenoreceptor blockade on acute lung injury (ALI) and high mobility group box-1 protein (HMGB1) expression in a rat model of sepsis. METHODS: Sepsis was induced in male rats by cecal ligation and puncture (CLP). Thirty adult male Sprague-Dawley rats were equally randomized to the Sham group, the CLP group, and the CLP+maleate group. Five hours after CLP, rats received an intraperitoneal injection of BRL-44408 maleate or the same volume of vehicle. Serum levels of TNF-α, IL-6, IL-10, HMGB1, and norepinephrine were measured at baseline, 6, 18, and 24h after CLP. Lung TNF-α, IL-6, IL-10, immunohistochemical and western blotting analysis of HMGB1, nuclear factor (NF)-κB activation, myeloperoxidase (MPO) activity, histological scores, and wet-to-dry weight ratio were determined 24h after CLP. In additional CLP and CLP+maleate groups, the 7 day survival rate was evaluated. RESULTS: Compared with the CLP group, serum TNF-α at 6h, HMGB1 at 18 and 24h, and norepinephrine at 6 and 18 h after CLP decreased in the CLP+maleate group. Lung TNF-α, IL-6, and HMGB1 expressions decreased at 24h after CLP. NF-κB activation, MPO activity, histological scores, and wet-to-dry weight ratio were lower in the CLP+maleate group than the CLP group. There was no significant difference in 7 day survival rate between the CLP and CLP+maleate groups. CONCLUSIONS: The α2A-adrenoreceptor blockade by a specific antagonist maleate improves sepsis-induced acute lung injury accompanied with depressed HMGB1 expression in rats. The mechanism seemed to be mediated partly through downregulation of the signal transductions of the NF-κB pathway.
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Lesão Pulmonar Aguda/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Proteína HMGB1/sangue , Imidazóis/farmacologia , Isoindóis/farmacologia , Receptores Adrenérgicos alfa 2/metabolismo , Sepse/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/microbiologia , Animais , Ceco/microbiologia , Ceco/cirurgia , Regulação para Baixo , Ativação Enzimática , Proteína HMGB1/metabolismo , Interleucina-10/sangue , Interleucina-6/sangue , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , NF-kappa B/metabolismo , Norepinefrina/sangue , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Sepse/complicações , Transdução de Sinais , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: To explore the association of the uric acid levels and coronary blood flow in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 276 STEMI patients undergoing primary PCI were enrolled and divided into 2 groups based upon the Thrombolysis in Myocardial Infarction (TIMI) flow grade. No-reflow was defined as TIMI Grade 0, 1 and 2 flows. The association of uric acid levels on admission with TIMI flow grade after PCI was assessed by multivariate Logistic regression. Major adverse cardiac events (MACE) were defined as death, non-fatal myocardial infarction and need for repeat percutaneous revascularization or coronary artery bypass grafting. RESULTS: The uric acid level was significantly higher in the no-reflow group (n = 57) than that of the normal-flow group (n = 219, 372 ± 111 vs 303 ± 102, P < 0.01). In-hospital MACEs were significantly higher in the patients with no reflow (8.8% vs 1.8%, P = 0.016). A uric acid level ≥ 345 mmol/L measured on admission had a 61.2% sensitivity and 77.5% specificity in predicting no-reflow at ROC curve analysis. At multivariate analyses, high plasma uric acid (OR 1.01, 95%CI 1.01 - 1.01, P < 0.01), neutrophil count (OR 1.02, 95%CI 1.00 - 1.06, P < 0.01), admission plasma glucose (OR 1.14, 95%CI 1.08 - 1.21, P < 0.01), time from pain to PCI (OR 1.67, 95%CI 0.46 - 5.97, P = 0.012), pre PCI thrombus score ≥ 4 (OR 2.67, 95%CI 1.29 - 5.13, P = 0.008), collateral circulation grade ≤ 1 (OR 1.86, 95%CI 1.27 - 2.73, P = 0.008), and Killip classes (OR 2.01, 95%CI 1.01 - 3.94, P = 0.042) were independent predictors of no-reflow post primary PCI. CONCLUSIONS: The plasma level of uric acid on admission is a strong and independent predictor of poor coronary blood flow following at post-primary PCI among STEMI patients. Uric acid levels may be a useful biomarker of risk stratification.
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Circulação Coronária , Infarto do Miocárdio/sangue , Fenômeno de não Refluxo/diagnóstico , Ácido Úrico/sangue , Idoso , Angioplastia Coronária com Balão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Prognóstico , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Brain natriuretic peptide (BNP) levels are elevated in patients with atrial fibrillation (AF). The aim of this study is to investigate the relation between the pre-procedural BNP level and the incidence of recurrence AF after circumferential pulmonary vein ablation (CPVA). METHODS: Plasma BNP level was measured before CPVA in 69 consecutive symptomatic paroxysmal AF (PAF) patients without heart failure symptom. Atrial thrombus was detected by transesophageal echocardiography in 15 patients and CPVA was not performed in these patients. CPVA was successful in the remaining 54 patients and followed up for 3 months. All patients were asked to keep a log of the duration and frequency of their symptoms and underwent 24 h ECG monitoring at least once per month after the ablation. RESULTS: At the end of follow up, 39 patients were free of AF recurrence (successful group) and 15 patients experienced AF recurrence (failure group). BNP concentration was below the heart failure range (< 500 ng/L) in 69.6% patients, but exceeded the normal range (0 - 144 ng/L) in 59.4% patients. Median baseline BNP level was significantly higher in failure group than in successful group (371.6 ng/L vs. 97.4 ng/L, P = 0.001). Left atrial (LA) dimension was also larger in failure group than in successful group [(53.3 ± 15.1) mm vs. (45.2 ± 11.2) mm, P = 0.036]. Moreover, BNP level was positively correlated with LA dimension (r = 0.574, P < 0.01). CONCLUSION: The pre-procedural BNP level and LA dimension are predictive of successful CPVA for PAF patients.
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Fibrilação Atrial/cirurgia , Ablação por Cateter , Peptídeo Natriurético Encefálico/sangue , Adulto , Idoso , Fibrilação Atrial/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Background: Talaromyces marneffei (T. marneffei) is an opportunistic fungal pathogen commonly found in human immunodeficiency virus (HIV) patients that often infects lymph nodes. Knowledge about the computed tomography (CT) characteristics of T. marneffei lymphadenopathy in HIV patients is limited. The aim of this study was to investigate the clinical and CT characteristics of T. marneffei lymphadenopathy to improve its diagnosis and promote recognition of this type of infection in radiology. Methods: Between February 2019 and June 2021, we retrospectively reviewed the clinical features and CT characteristics of T. marneffei lymphadenopathy in 21 HIV patients. Results: The clinical symptoms of T. marneffei infection are non-specific. Anemia (100%), fever (85.7%) and cough and sputum production (76.2%) were the most frequent symptoms. Multiple lymphadenopathies, mainly in the mediastinum (76.2%) and mesentery (82.4%), can be fused (14.3%) and necrotic (52.4%), with slight (41.7%) and moderate enhancement (58.3%) that is heterogeneous. In addition to involving the lymph nodes, the lesions involved the lungs (81.0%), liver and spleen (42.9%), and small intestine (14.3%). Conclusions: T. marneffei is prone to affecting lymph nodes and extranodal organs in HIV patients. Although the clinical manifestations of T. marneffei infection are not specific, the possibility of T. marneffei infection should be considered if CT findings indicate multiple lesion sites.
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Background and Purpose: We have previously reported a cardioprotective effect with Xin-Ji-Er-Kang (XJEK) treatment in mice with myocardial infarction (MI)-induced heart failure, but no report about its potential functions in myocardial ischemia-reperfusion (MIR) injury. Here we studied the therapeutic effects of XJEK on MIR injury and investigated the mechanisms involved. Experimental Approach: MIR model of Balb/c mice induced by left anterior descending coronary artery ligation for half an hour, followed by reperfusion, was utilized to study the potential therapeutic effects of XJEK on MIR-induced cardiac injury. Ultra-performance liquid chromatography tandem Orbitrap mass spectrometry platform was used for studying serum lipid metabolic signatures. Key Results: MIR caused cardiac dysfunctions, cardiac injury, myocardial fibrosis, and increased inflammation, and all the observed abnormalities caused by MIR were largely corrected by XJEK treatment. Mechanistically, XJEK exerts its cardioprotective effect in the context of MIR injury by suppressing MIR-induced inflammation and dysregulation of serum lipid metabolism. Conclusion and Implications: We have demonstrated for the first time that XJEK protects heart from MIR injury by restoring dysregulated lipidomics. Our data provide new evidence to support a therapeutic effect for XIEK on MIR-induced cardiac injury, and pave the way for exploring the therapeutic potential of XJEK in large animal study and early clinical trial.
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OBJECTIVE: To investigate the alteration of plasma C-reactive protein(CRP) count in patients with non-valvula atrial fibrillation combining thrombosis. METHODS: A total of 154 patients with non-valvula atrial fibrillation were divided into thrombus group (n = 46) and non-thrombus group (n = 108) in accordance with transesophageal echocardiography (TEE) results. The concentration of CRP by scattering turbidimetry, D-dimer by immunoturbidmetry, left atrium diameter (LAd), fraction shortening (FS) and left ventricular ejection fraction (LVEF) by TEE or echocardiography were detected. Logistic multi-factors regression analysis was performed. RESULTS: There were significant differences in CRP [(5.77 ± 6.37) mg/L vs (1.73 ± 2.39) mg/L, P = 0.003], LAd [(59.86 ± 10.70) mm vs (47.97 ± 13.19) mm, P < 0.001] and LVEF [(58.75 ± 8.28)% vs (64.10 ± 6.75)%, P < 0.001] between thrombus group and non-thrombus group. The results of logistic regression analysis found CRP ≥ 1.33 mg/L (OR 2.856, 95%CI 1.235 - 6.600, P = 0.014) and LAd ≥ 54.5 mm (OR 4.236, 95%CI 1.877 - 9.562, P = 0.001) were independent risk factors of patients with non-valvula atrial fibrillation combining with thrombosis. CONCLUSIONS: CRP and LAd are independent risk factors for patients with non-valvula atrial fibrillation combining with thrombosis. Inflammation may involve with the formation of thrombosis.
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Fibrilação Atrial/metabolismo , Proteína C-Reativa/metabolismo , Trombose/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , UltrassonografiaRESUMO
Chronic obstructive pulmonary disease (COPD) often tends to respond poorly to glucocorticoid (GC) therapy. Reduced Histone deacetylase-2 (HDAC-2) activity is an important mechanism behind this GC insensitivity. In this study, we investigated the effects of three phosphodiesterase inhibitors (PDEIs), with an anti-inflammatory propensity, on cigarette smoke (CS)-induced pulmonary inflammation and HDAC-2 activity. Male C57BL/6 mice were exposed to cigarette smoke (CS) over the course of 30 weeks. Administration of the PDEIs commenced from the 29th week and followed a schedule of once daily treatments, 5 days a week, for 2 weeks. Roflumilast (ROF) was administered intragastrically (5 mg·kg-1 ), while pentoxifylline (PTX) (10 mg·kg-1 ) and theophylline (THEO) (10 mg·kg-1 ) were administered intraperitoneally, either alone or in combination with a GC (triamcinolone acetonide or TRI, 5 mg·kg-1 , i.m., single injection). Lung morphometry, as well as the activity of HDAC-2, pro-inflammatory cytokines and reactive oxygen species (ROS) were assessed at the end of the 30-week course. CS exposure was associated with a reduction in HDAC-2 activity and the up-regulation of ROS expression. PTX, ROF, and THEO administration led to the partial restoration of HDAC-2 activity, which was favorably associated with the reduction of ROS expression. However, combining TRI to any of these PDEIs did not synergistically augment HDAC-2 activity. Inactivation of HDAC-2 due to long-term CS exposure is closely related to exaggerated oxidative stress, and this reduced HDAC-2 activity could partially be restored through the use of PDEIs. This finding provides a potential novel approach for further clinical research.