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Objective: To evaluate potential improvements in the diagnosis of thyroid nodules when conventional ultrasound (US) is combined with contrast-enhanced US (CEUS). Methods: We recruited 515 participants with 323 malignant and 192 benign nodules, who underwent both US and CEUS examinations at 8 different medical centers in China between October 2020 and October 2021. We assessed the malignancy of thyroid nodules in US using the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TIRADS). Diagnostic criteria for US and US + CEUS were developed by investigators based on evaluations of sonographic features. Using multivariate logistic regression and receiver operating characteristic (ROC) analysis, we compared diagnostic performance between the 2 methods based on criteria identified by investigators and via statistical models. Results: On the basis of diagnostic criteria identified by investigators, we measured statistically significant differences in area under the curve (AUC) values between ACR TIRADS (0.83) and CEUS TIRADS (0.87; P < .001). On the basis of diagnostic regression models, we found statistically significant differences in AUC values between US (0.76) and US + CEUS (0.84; P = .001). Models based on US + CEUS outperformed those based on US alone (Akaike information criterion of 347.7 and significant improvement in integrated discrimination). These results were confirmed by similar analyses applied to a validation cohort. Conclusion: The accuracy of conventional US for differentiating between benign and malignant thyroid nodules can be improved by combining this approach with CEUS.
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Background Current guidelines recommend the use of conventional US for risk stratification and management of thyroid nodules. However, fine-needle aspiration (FNA) is often recommended in benign nodules. Purpose To compare the diagnostic performance of multimodality US (including conventional US, strain elastography, and contrast-enhanced US [CEUS]) with the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) in the recommendation of FNA for thyroid nodules to reduce unnecessary biopsies. Materials and Methods In this prospective study, 445 consecutive participants with thyroid nodules from nine tertiary referral hospitals were recruited between October 2020 and May 2021. With univariable and multivariable logistic regression, the prediction models incorporating sonographic features, evaluated with interobserver agreement, were constructed and internally validated with bootstrap resampling technique. In addition, discrimination, calibration, and decision curve analysis were performed. Results A total of 434 thyroid nodules confirmed at pathologic analysis (259 malignant thyroid nodules) in 434 participants (mean age, 45 years ± 12 [SD]; 307 female participants) were included. Four multivariable models incorporated participant age, nodule features at US (proportion of cystic components, echogenicity, margin, shape, punctate echogenic foci), elastography features (stiffness), and CEUS features (blood volume). In recommending FNA in thyroid nodules, the highest area under the receiver operating characteristic curve (AUC) was 0.85 (95% CI: 0.81, 0.89) for the multimodality US model, and the lowest AUC was 0.63 (95% CI: 0.59, 0.68) for TI-RADS (P < .001). At the 50% risk threshold, 31% (95% CI: 26, 38) of FNA procedures could be avoided with multimodality US compared with 15% (95% CI: 12, 19) with TI-RADS (P < .001). Conclusion Multimodality US had better performance in recommending FNA to avoid unnecessary biopsies than the TI-RADS. Clinical trial registration no. NCT04574258 © RSNA, 2023 Supplemental material is available for this article.
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Nódulo da Glândula Tireoide , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Biópsia por Agulha Fina , Imagem Multimodal , Estudos Prospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassonografia/métodosRESUMO
ABSTRACT Background Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis. Materials and Methods PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software. Results A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results. Conclusions The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.
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RATIONALE AND OBJECTIVES: With the advantage of minimizing damage and preserving more functional lung tissue, limited surgery is considered depend on the lymph node (LN) involvement situation. However, occult lymph node metastasis (OLM) may be ignored by limited surgery and become a risk factor for local recurrence after surgical resection. The aim of this study was to assess the risk factors for OLM based on computed tomography enhanced image in patients with clinical lung adenocarcinoma (ADC). MATERIALS AND METHODS: From January 2016 to July 2022, 707 patients with clinical stage IA-IIA ADC underwent lobectomy with systematic LN dissection and were divided into training and validation group based on different institution. Univariate analysis followed by multivariable logistic regression were performed to estimate different risk factors of OLM. A predictive model was established with visual nomogram and external validation, and evaluated in terms of accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: Fifty-nine patients were diagnosed with OLM (11.9%), and four independent predictors of LN involvement were identified: larger consolidation diameter (odds ratio [OR], 2.35, 95% confidence interval [CI]: 1.06, 5.22, p = 0.013), bronchovascular bundle thickening (OR, 1.99, 95% CI: 1.00, 3.95, p = 0.049), lobulation (OR, 2.92, 95% CI: 1.22, 6.99, p = 0.016) and obstructive change (OR, 1.69, 95% CI: 1.17, 6.16, p = 0.020). The model showed good calibration (Hosmer-Lemeshow goodness-of-fit, p = 0.816) with an AUC of 0.821 (95% CI: 0.775, 0.853). For the validation group, the AUC was 0.788 (95% CI: 0.732, 0.806). CONCLUSION: Our predictive model can non-invasively assess the risk of OLM in patients with clinical stage IA-IIA ADC, enable surgeons perform an individualized prediction preoperatively, and assist the clinical decision-making procedure.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Several studies have explored the impact of BMI on size and composition of urinary stones. Because there were controversies, a meta-analysis was necessary to be carried out to provide some evidence of the relationship of BMI and urolithiasis. MATERIALS AND METHODS: PubMed, Medline, Embase, Web of Science databases, and the Cochrane Library were searched up to August 12th 2022 for eligible studies. The urolithiasis patients were summarized into two groups: BMI < 25 and ≥ 25 kg/m2. Summary weighted mean difference (WMD), relative risk (RR) and 95% confidence intervals (CI) were calculated through random effects models in RevMan 5.4 software. RESULTS: A total of fifteen studies involving 13,233 patients were enrolled in this meta-analysis. There was no significant correlation of BMI and size of urinary stone (WMD -0.13mm, 95% CI [-0.98, 0.73], p = 0.77). Overweight and obesity increased the risk of uric acid stones in both genders and in different regions (RR=0.87, [95% CI] = 0.83, 0.91, p<0.00001). There was a higher risk of calcium oxalate stones formation in overweight and obesity group in total patients (RR=0.95, [95% CI] = 0.91, 0.98, p = 0.006). The relationship of BMI and calcium phosphate was not observed in this meta-analysis (RR=1.12, [95% CI] = 0.98, 1.26, p = 0.09). Sensitivity analysis was performed and indicated similar results. CONCLUSIONS: The current evidence suggests a positive association between BMI and uric acid and calcium oxalate stones. It would be of great guiding significance to consider losing weight when treating and preventing urinary stones.
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Cálculos Urinários , Urolitíase , Humanos , Feminino , Masculino , Índice de Massa Corporal , Sobrepeso/complicações , Oxalato de Cálcio , Ácido Úrico , Urolitíase/etiologia , Obesidade/complicaçõesRESUMO
Left atrial appendage (LAA) is a finger-like muscular extension of the left atrium, and it is the most prominent site for cardiac thrombus in patients with atrial fibrillation. Congenital absence of LAA could be incidentally detected in patient with ischemic stroke and atrial fibrillation. Although it is considered to be an extremely rare cardiac anomaly, its clinical significance remains unknown and there is no clear consensus in the management strategy in those patients. Therefore, we report a case of an incidentally noted congenital absence of LAA in a 68-year-old woman being planned for LAA closure.
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Papillary thyroid carcinoma (PTC) has a relatively good prognosis, yet there are some invasive PTC cases with worse clinicopathological features and poor outcome. Cancer-associated fibroblasts (CAFs) play an important role in cancer invasion and metastasis. This study aimed to investigate the expression of marker proteins of CAFs in PTC and their correlations with clinicopathological features through immunohistochemistry. The medical records of 125 PTC patients were reviewed in this study, whose specimens were retrieved for immunohistochemistry. Four CAFs marker proteins, FAP fibroblast activated protein (FAP), α-smooth muscle actin (α-SMA), Vimentin and platelet-derived growth factor receptor-α(PDGFR-α), were stained and scored. Then, statistical analyses were performed. The immunoreactivity scores of FAP and α-SMA correlated with tumor size, BRAF mutation, extrathyroidal, invasion, pathological subtype, lymph node metastasis and ATA risk stratification. Moreover, binary logistic regression analysis and receiver operating characteristic curves showed that high FAP and α-SMA immunoreactivity scores were risk factors for extrathyroidal invasion, BRAF mutation, multi-focality and lymph node metastasis (especially N1b) with good sensitivity and accuracy in prediction. A better performance was found in FAP than α-SMA. Strong expressions of CAFs were risk factors for worse thyroid cancer clinicopathological features. FAP was the better CAFs marker for PTC.
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Fibroblastos Associados a Câncer , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Metástase Linfática , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
Carbon nanomaterials (CNMs) are ubiquitous in our daily lives because of the outstanding physicochemical properties. CNMs play curial parts in industrial and medical fields, however, the risks of CNMs exposure to human health are still not fully understood. In view of, it is becoming extremely difficult to ignore the existence of the toxicity of CNMs. With the increasing exploitation of CNMs, it's necessary to evaluate the potential impact of these materials on human health. In recent years, more and more researches have shown that CNMs are contributed to the cancer formation and metastasis after long-term exposure through epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) which is associated with cancer progression and invasion. This review discusses CNMs properties and applications in industrial and medical fields, adverse effects on human health, especially the induction of tumor initiation and metastasis through EMT and CSCs procedure.
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Nanoestruturas , Neoplasias , Humanos , Carbono/química , Transição Epitelial-Mesenquimal , Neoplasias/induzido quimicamente , Nanoestruturas/toxicidade , Células-Tronco Neoplásicas/patologiaRESUMO
Infection is the most common complications of percutaneous nephrolithotomy (PCNL) in treating urinary calculi. However, the risk factors for developing infectious complications after surgery have not been clarified, and the predictive value of some factors is controversial. This study aimed to assess the risk factors for postoperative infectious complications of PCNL. We performed a systematic search of PubMed, Web of Science, Cochrane Library, and EMBASE to obtain studies reporting risk factors for postoperative infection complications after PCNL. In this review, demographic factors, laboratory test factors, and perioperative factors were evaluated. The odds ratio (OR) or mean difference (MD) with a 95% confidence interval (CI) was calculated to assess the risk factors. A total of 18 studies were included, with a total of 7161 study patients with a mean age of 46.4 to 55.5 years and an incidence of infectious complications after PCNL ranging from 2.4% to 40.4%. Twelve factors were identified as independent risk factors for post-PCNL infection complications (P < 0.05), female (OR = 1.60, 95% CI 1.23-2.07), positive urine culture (UC) (OR = 3.16, 95% CI 2.11-4.74), positive renal pelvis urine culture (RPUC) (OR = 5.81, 95% CI 1.75-19.32), positive stone culture (SC) (OR = 5.11, 95% CI 1.46-17.89), positive urine leukocyte (OR = 3.61, 95% CI 2.45-5.34), infected stones (OR = 7.00, 95% CI 1.27-38.55), elevated blood leukocyte (MD = 0.71, 95% CI 0.31-1.10), elevated neutrophil-to-lymphocyte ratio (NLR) (MD = 0.55, 95% CI 0.43-0.66), preoperative stenting (OR = 1.55, 95% CI 1.10-2.20), multiple puncture access (OR = 2.58, 95% CI 1.75-3.82), prolonged operative time (MD = 10 20, 95% CI 4.80-15.60), and postoperative residual stone (OR = 1.56, 95% CI 1.24-1.98). Female, UC positivity, RPUC positivity, SC positivity, urine leukocyte positivity, infected stones, elevated peripheral blood leukocytes, elevated NLR, preoperative stent implantation, multiple puncture channels, prolonged operation time, and postoperative residual stones were identified as independent risk factors for infection complications after PCNL.
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Cálculos Renais , Nefrolitotomia Percutânea , Humanos , Feminino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/efeitos adversos , Cálculos Renais/terapia , Fatores de Risco , Pelve Renal , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Not required for Clinical Vignette.
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Neuroma , Neoplasias da Glândula Tireoide , Humanos , Esvaziamento Cervical/efeitos adversos , Neuroma/etiologia , Neuroma/cirurgia , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
Our study was aimed to evaluate the postoperative outcomes of Mini Percutaneous Nephrolithotomy (Mini-PCNL) and Standard Percutaneous Nephrolithotomy (Standard-PCNL) to determine the optimum option for patients with renal calculi. For publications published between January 2010 and April 2021, a comprehensive search of the PubMed, Cochrane Library, Web of Science, and EMBASE databases was done. The literatures were chosen based on the criteria for inclusion and exclusion. After the data were retrieved and the quality was assessed, the meta-analysis was performed using Review Manager Software (RevMan 5.4.1, Cochrane Collaboration, Oxford, UK). We selected 20 trials with a total of 4953 people out of 322 studies. There were 2567 patients treated with Mini-PCNL and 2386 patients treated with Standard-PCNL. Meta-analysis results showed no difference in stone-free rates (SFR, P = 0.93), fever (P = 0.83), and postoperative pain (VAS score) (P = 0.21) between Mini-PCNL and Standard-PCNL. Patients in the Mini-PCNL group experienced shorter hospital stay (P < 0.0001), less hemoglobin drop (P < 0.00001), less blood transfusion (P < 0.00001), higher postoperative tubeless (P = 0.0002), and fewer complications including bleeding (P = 0.01), perforation (P = 0.03), and leakage (P = 0.01). Compared with Standard-PCNL, operative time was longer in the Mini-PCNL group (P = 0.0005). Mini-PCNL had a shorter hospital stay, less hemoglobin drop, less blood transfusion, greater postoperative tubeless, fewer complications, and a longer operational time when compared to Standard-PCNL. SFR, fever, and postoperative pain were similar in both of them. Mini-PCNL may be a superior option for patients with proper size renal calculi.
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Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Febre , Hemoglobinas , Humanos , Cálculos Renais/cirurgia , Tempo de Internação , Nefrolitotomia Percutânea/efeitos adversos , Nefrolitotomia Percutânea/métodos , Nefrostomia Percutânea/efeitos adversos , Nefrostomia Percutânea/métodos , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Castleman's disease (CD) is a lymphatic proliferative disorder of unknown cause and is rarely seen clinically. It has been divided into unicentric and multicentric types. Unicentric CD (UCD) occurs as a solitary enlarged mass and mediastinal lymph nodes are the most common site. Surgical excision has proven to be curative for UCD. Multicentric CD (MCD) appears as a systemic disease with peripheral lymphadenopathy. MCD had a poor response to surgery and monoclonal antibodies with rituximab have become a research hotspot. CASE SUMMARY: A 44-year-old woman presented with a pancreatic mass during routine physical examination. She had no obvious symptoms, such as fever, abdominal pain, abdominal distension, or jaundice. Ultrasound examination indicated a hypoechoic mass between the body of the pancreas, left lobe of the liver and stomach. It had a clear boundary, irregular shape, uneven echo, and no obvious blood flow signals. To clarify the diagnosis, contrast-enhanced ultrasound examination was performed, which showed a benign pancreatic lesion. Neuroendocrine or solid pseudopapillary tumor was a possible diagnosis. The patient underwent further contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging, which were suggestive of solid pseudopapillary tumor or neuroendocrine tumor. All the examinations failed to give a definitive diagnosis, and the patient underwent surgery. The final pathological and immunohistochemical results showed that the mass was CD. CONCLUSION: This case highlights when lymphadenopathy is encountered clinically, CD should be considered and a biopsy should be performed.
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OBJECTIVES: To evaluate the efficacy and cost effectiveness of two-stage percutaneous nephrolithotomy (PCNL) in complex renal calculus disease. METHODS: The clinical data of 106 patients who underwent two-stage PCNL at the Second Affiliated Hospital of Kunming Medical University from January 2017 to May 2022 were analyzed. In order to select more accurate timing and strategies to reduce costs and surgery risk in two-stage PCNL patients, different parameters were measured-including the preoperative urinary tract infection, intraoperative bleeding, operative time, postoperative stone clearance and treatment costs. Patients were divided into group A and group B according to different timings of two-stage PCNL operation. Group A included patients who underwent two-stage PCNL during their period of hospitalization 5 to 9 days after the one-stage PCNL. Group B comprised patients who were re-hospitalized for two-stage PCNL 29 to 35 days after the one-stage PCNL. RESULTS: There were statistically significant differences in the influence of stone diameter and operation time in intraoperative blood loss of PCNL in 106 patients (p < 0.001). Compared with one-stage PCNL, the intraoperative hemoglobin loss and hematocrit loss means of patients with two-stage PCNL were decreased, the stone diameter mean of was smaller, and the mean operative time was diminished (p < 0.001). There were no significant differences in the hemoglobin loss, hematocrit loss and stone clearance rate means between group A and group B (p > 0.05). The urinary tract infection rate in group A was lower than the one in group B, and the average treatment cost was lower than the one in group B (p = 0.006, p < 0.001, respectively). CONCLUSIONS: Intraoperative bleeding in PCNL is influenced by stone diameter and operative time. Two-stage PCNL displays smaller calculi, shorter operation time and lower intraoperative blood loss than one-stage PCNL. Patients who had no surgical contraindication could undergo two-stage PCNL during the same hospitalization 5 to 9 days after one-stage PCNL to avoid rehospitalization. This approach could reduce the risk of urinary tract infection of indwelling nephrostomy tube and decrease the economic burden of patients.
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Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Humanos , Perda Sanguínea Cirúrgica , Resultado do Tratamento , Estudos Retrospectivos , Cálculos Renais/cirurgiaRESUMO
OBJECTIVES: To retrospectively investigate whether radiological and clinicopathological characteristics were associated with the presence of stage IA-IIA lung adenocarcinoma in patients at high risk for a postoperative recurrence. MATERIALS AND METHODS: Three hundred twelve patients with biopsy-proven node-negative early-stage (IA-IIA) lung adenocarcinoma met the inclusion criteria for this study. Demographics data and histopathological findings were collected from medical records. Computed tomography (CT) performed approximately 1 month before surgery was manually scored using 23 CT descriptors. Univariate analyses were applied to demonstrate an association between clinicopathological and radiological features and 2-/5-year recurrences. Multivariate logistic regression was performed to assess the ability of radiological and clinicopathological features to discriminate low and high-risk factors for recurrence. A ROC curve was used to evaluate prediction performance. RESULTS: Univariate analysis revealed that the 2-year recurrence was associated with six radiological features and two clinicopathological features, while 5-year recurrence was associated with five radiological features and two clinicopathological features. A multivariate logistic regression model of combined clinicopathological and radiological features showed that stage IIA (OR = 2.87), solid texture (solid part > 50 %: OR = 4.81; solid part = 100 %: OR = 3.61), pleural attachment (OR = 3.97) and bronchovascular bundle thickening (OR = 2.16) were associated with the independent predictors of 2-year recurrence, and stage IIA (OR = 3.52), solid texture (solid part > 50 %: OR = 3.56; solid part = 100 %: OR = 2.44) and pleural attachment (OR = 4.57) were associated with 5-year recurrence. Combined radiological and clinicopathological features could be significant indicators of 2- and 5-year recurrences (AUC = 0.784 and AUC = 0.815, respectively). CONCLUSIONS: The combination of radiological and clinicopathological features has the potential to help predict postoperative recurrence in patients with stage IA-IIA lung adenocarcinomas and guide oncologists and patients whether to undergo additional treatment after surgery.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Icariin is the main active compound extracted from epimedium Flavonoids (EFs) and involved in regulation of cell behaviors (proliferation, apoptosis, and autophagy etc.) for many cell types, but the effect of Icariin on airway smooth muscle cells (ASMCs) is still unknown. The aim of the present study is to examine the role of Icariin on rat ASMCs proliferation, apoptosis and autophagy. CKK8 assay showed that Icariin inhibited rat ASMCs growth in dose-time-dependent manner, and the flow cytometry assay showed that the Icariin interfered with ASMCs cell cycle, when treated with Icariin, S phase shortened while G2 phase extended, cyclin E1 and cyclinA1 gene and protein expression decreased. Next apoptosis was detected, Flow cytometry and TdTmediated dUTP Nick-End Labeling (TUNEL) assay showed that Icariin promoted ASMCs apoptosis, and enhanced apoptosis protein cleaved-caspase-3 expression. Finally, it was found Icariin induced rat ASMCs autophagy, with enhancement expression of autophagy marker LC3 II. In conclusion, Icariin inhibited ASMCs proliferation while promoted apoptosis and autophagy, revealing its potential role in treatment of airway remodeling in asthma.
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The proliferation of cardiac fibroblasts (CFs) and excessive deposition of extracellular matrix are the predominant pathological characteristics of cardiac fibrosis. As the largest member of the nucleotidebinding domain and leucinerich repeat (NLR) family, NLRC5 has been shown to be pivotal in the development of hepatic fibrosis. However, whether NLRC5 is involved in the pathogenesis of cardiac fibrosis remains to be elucidated. The present study aimed to investigate the role of NLRC5 and its mechanisms in regulating cardiac fibrosis. CFs were stimulated with transforming growth factor (TGF)ß1 for various times and the mRNA and protein expression of NLRC5 was assessed using reverse transcriptionquantitative polymerase chain reaction and western blot analysis, respectively. In addition, CFs were transfected with small interfering (si)RNA targeting NLRC5 or scramble siRNA for 24 h and then stimulated with TGFß1 for 24 h. Subsequently, cell proliferation was measured using an MTT assay, whereas cell migration was evaluated using a Transwell migration assay. The protein expression levels of αsmooth muscle actin, collagen I, connective tissue growth factor, phosphorylatedSmad3 and Smad3 were measured using western blot analysis. The results demonstrated that NLRC5 was upregulated in TGFß1induced CFs. The knockdown of NLRC5 significantly inhibited cell proliferation and migration, and suppressed myofibroblast differentiation and the expression of profibrotic molecules in TGFß1treated CFs. Furthermore, the knockdown of NLRC5 attenuated TGFß1induced phosphorylation of small mothers against decapentaplegic (Smad)3 in the CFs. The results of the present study indicated that NLRC5 acted as a key regulator of pathological cardiac fibrosis, and NLRC5 silencing ameliorated cardiac fibrosis by inhibiting the TGFß1/Smad3 signaling pathway. These results suggested that NLRC5 may be a novel target for attenuating cardiac fibrosis.
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Inativação Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Miocárdio/metabolismo , Miocárdio/patologia , Proteínas NLR/genética , Transdução de Sinais , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Movimento Celular , Proliferação de Células , Feminino , Fibroblastos/metabolismo , Fibrose , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas NLR/metabolismo , Fosforilação , Ratos Sprague-Dawley , Regulação para CimaRESUMO
The proliferation of cardiac fibroblasts (CFs) and deposition of extracellular matrix (ECM) proteins are pivotal in the development of cardiac fibrosis. Recent studies have indicated that diosgenin may inhibit high glucoseinduced renal tubular fibrosis; however, to the best of our knowledge, no studies have focused on the effects of diosgenin on cardiac fibrosis. Therefore, the present study aimed to explore the effects of diosgenin on angiotensin II (Ang II)induced ECM remodeling, and its possible mechanism in rat CFs. CFs were preincubated with diosgenin (1, 5 and 10 µM) for 24 h and were then stimulated with Ang II (100 nM) for 24 h. Cell proliferation was estimated using the MTS assay. The expression levels of αSMA, fibronectin, collagen I, TGFß1, in addition to phosphorylation of Smad3 were detected by western blotting. The results demonstrated that diosgenin inhibited Ang IIinduced CF proliferation and the differentiation of CFs to myofibroblasts. In addition, diosgenin was able to inhibit Ang IIinduced ECM expression in rat CFs. Furthermore, diosgenin inhibited Ang IIinduced expression of transforming growth factorß1 (TGFß1) and Smad3 phosphorylation in CFs. Taken together, these results suggest that diosgenin may inhibit Ang IIinduced ECM remodeling by suppressing the TGFß1/Smad3 signaling pathway in rat CFs. Therefore, diosgenin may possess therapeutic potential for the treatment of cardiac fibrosis.
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Angiotensina II/toxicidade , Diosgenina/farmacologia , Matriz Extracelular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Actinas/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibronectinas/metabolismo , Miocárdio/citologia , Fosforilação/efeitos dos fármacos , Ratos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Cardiac arrest (CA), if untreated for more than 5 min, can induce severe brain damage, the underlying mechanism of which is still unclear. Previous studies have indicated that high-mobility group box 1 (HMGB1), a nuclear protein implicated in several inflammatory disorders, is involved in the inflammatory processes following brain ischemia. However, the role of HMGB1 in brain dysfunction after CA is yet to be determined. In a rat CA model, HMGB1 protein expression was higher at 1, 3, and 7 days post-CA, compared to that in naïve and sham-treated rats. Following injection of HMGB1 antibody (anti-HMGB1) into the cerebral ventricles, neurological deficit scores were significantly decreased in the CA group as compared to that in the naïve and sham group. Nissl staining showed significant neuronal loss in the hippocampal CA1 region following CA, which was significantly attenuated by anti-HMGB1-treatment (10 and 50 µg) in comparison with the vehicle-injected control. CA induced a significant increase in the levels of the cytokine interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α) in the hippocampus as revealed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Treatment with anti-HMGB1 significantly inhibited IL-1ß and TNF-α expression. Our study suggests that HMGB1 contributes significantly to CA-induced brain dysfunction and that inhibiting HMGB1 function and expression may be an effective therapeutic approach to CA-induced ischemic brain injury.
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Lesões Encefálicas/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Citocinas/metabolismo , Proteína HMGB1/fisiologia , Animais , Anticorpos/administração & dosagem , Anticorpos/farmacologia , Isquemia Encefálica/metabolismo , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/imunologia , Parada Cardíaca/complicações , Interleucina-1beta/antagonistas & inibidores , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Ratos , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Coronary artery aneurysm or ectasia was reported in approximately 15% to 25% of the affected children, particularly in the proximal end of the main blood vessel and the left anterior descending part. Rare patients have been reported with aneurysm in the distal end of the right coronary artery. In this case report, we present a rare case with aneurysm in the distal end of the right coronary artery. Multi-slice computed tomography was performed for the coronary angiography. Aspirin (10 mg/kg body weight per day) and gamma globulin (2 kg/kg body weight) was administrated via intravenous injection. The patient is currently in a healthy status with a 12-month follow up.