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1.
Sci Rep ; 14(1): 6198, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486013

RESUMO

Accurately identification of the seizure onset zone (SOZ) is pivotal for successful surgery in patients with medically refractory epilepsy. The purpose of this study is to improve the performance of model predicting the epilepsy surgery outcomes using genetic neural network (GNN) model based on a hybrid intracranial electroencephalography (iEEG) marker. We extracted 21 SOZ related markers based on iEEG data from 79 epilepsy patients. The least absolute shrinkage and selection operator (LASSO) regression was employed to integrated seven markers, selected after testing in pairs with all 21 biomarkers and 7 machine learning models, into a hybrid marker. Based on the hybrid marker, we devised a GNN model and compared its predictive performance for surgical outcomes with six other mainstream machine-learning models. Compared to the mainstream models, underpinning the GNN with the hybrid iEEG marker resulted in a better prediction of surgical outcomes, showing a significant increase of the prediction accuracy from approximately 87% to 94.3% (P = 0.0412). This study suggests that the hybrid iEEG marker can improve the performance of model predicting the epilepsy surgical outcomes, and validates the effectiveness of the GNN in characterizing and analyzing complex relationships between clinical data variables.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Eletrocorticografia/métodos , Epilepsia/genética , Epilepsia/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Aprendizado de Máquina , Resultado do Tratamento , Eletroencefalografia/métodos
2.
Seizure ; 117: 126-132, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417211

RESUMO

PURPOSE: Focal cortical dysplasia (FCD) is a common etiology of drug-resistant focal epilepsy. Visual identification of FCD is usually time-consuming and depends on personal experience. Herein, we propose an automated type II FCD detection approach utilizing multi-modal data and 3D convolutional neural network (CNN). METHODS: MRI and positron emission tomography (PET) data of 82 patients with FCD were collected, including 55 (67.1%) histopathologically, and 27 (32.9%) radiologically diagnosed patients. Three types of morphometric feature maps and three types of tissue maps were extracted from the T1-weighted images. These maps, T1, and PET images formed the inputs for CNN. Five-fold cross-validations were carried out on the training set containing 62 patients, and the model behaving best was chosen to detect FCD on the test set of 20 patients. Furthermore, ablation experiments were performed to estimate the value of PET data and CNN. RESULTS: On the validation set, FCD was detected in 90.3% of the cases, with an average of 1.7 possible lesions per patient. The sensitivity on the test set was 90.0%, with 1.85 possible lesions per patient. Without the PET data, the sensitivity decreased to 80.0%, and the average lesion number increased to 2.05 on the test set. If an artificial neural network replaced the CNN, the sensitivity decreased to 85.0%, and the average lesion number increased to 4.65. SIGNIFICANCE: Automated detection of FCD with high sensitivity and few false-positive findings is feasible based on multi-modal data. PET data and CNN could improve the performance of automated detection.


Assuntos
Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Displasia Cortical Focal , Imageamento por Ressonância Magnética/métodos , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Redes Neurais de Computação , Tomografia por Emissão de Pósitrons/métodos
3.
Oncogene ; 43(10): 703-713, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218898

RESUMO

Aberrant activation of the epithelial-mesenchymal transition (EMT) pathway drives the development of solid tumors, which is precisely regulated by core EMT-related transcription factors, including Twist1. However, the expression pattern and regulatory mechanism of Twist1 in the progression of bladder cancer is still unclear. In this study, we explore the role of Twist1 in the progression of bladder cancer. We discovered that the EMT regulon Twist1 protein, but not Twist1 mRNA, is overexpressed in bladder cancer samples using RT-qPCR, western blot and immunohistochemistry (IHC). Mechanistically, co-immunoprecipitation (Co-IP) coupled with liquid chromatography and tandem mass spectrometry identified USP5 as a binding partner of Twist1, and the binding of Twist1 to ubiquitin-specific protease 5 (USP5) stabilizes Twist through its deubiquitinase activity to activate the EMT. Further studies found that USP5 depletion reduces cell proliferation, invasion and the EMT in bladder cancer cells, and ectopic expression of Twist1 rescues the adverse effects of USP5 loss on cell invasion and the EMT. A xenograft tumor model was used to reconfirmed the inhibitor effect of silencing USP5 expression on tumorigenesis in vivo. In addition, USP5 protein levels are significantly elevated and positively associated with Twist1 levels in clinical bladder cancer samples. Collectively, our study revealed that USP5-Twist1 axis is a novel regulatory mechanism driving bladder cancer progression and that approaches targeting USP5 may become a promising cancer treatment strategy.


Assuntos
Proteína 1 Relacionada a Twist , Neoplasias da Bexiga Urinária , Humanos , Animais , Proteína 1 Relacionada a Twist/genética , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária , Transformação Celular Neoplásica , Modelos Animais de Doenças , Proteases Específicas de Ubiquitina
4.
J Biomater Sci Polym Ed ; 35(3): 330-344, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38032009

RESUMO

In this study, the PEG-Glu-Lys-Glu copolymer drug delivery system (GO/PEG-Glu-Lys-Glu) is prepared using glutamate-lysine-glutamate (Glu-Lys-Glu) modified polyethylene glycol (PEG) and connected graphene oxide nanosheets (GO). The multiple carboxyl groups of Glu-Lys-Glu and π-π interactions of GO can increase drug loading rate, and the fluorescence characteristics of GO could monitor the distribution of drug-loading systems in cells and the uptake of cells without the need for external dyes. Paclitaxel (PTX) is loaded via reduction-responsive disulfide bonds as a model medicine to examine the drug delivery potential of GO/PEG-Glu-Lys-Glu. The results showed that the drug loading content of PEG-Glu-Lys-Glu and GO/PEG-Glu-Lys-Glu to PTX is 7.11% and 8.97%, and the loading efficiency is 71.05% and 89.68%, respectively. It's speculated that the π-π interaction between GO and PTX improved the drug-loading capacity and efficiency of GO/PEG-Glu-Lys-Glu. In vitro, in a simulated drug release test, at 48 h, the release of PTX was 85.51% at pH 5.0, 65.12% and 38.32% at pH 6.5 and 7.4, respectively. The cytotoxicity assay results showed that GO/PEG-Glu-Lys-Glu cell inhibition rate to MCF-7 cells was 7.36% at 72 h. The cell inhibition rate of GO/PEG-Glu-Lys-Glu/PTX system at 72 h was 92%, equivalent to free PTX. Therefore, the GO/PEG-Glu-Lys-Glu drug delivery system has the characteristics of good biocompatibility and sustainable release of PTX, which is expected to be applied in the field of tumor therapy.


Assuntos
Dipeptídeos , Grafite , Lisina , Polietilenoglicóis , Humanos , Polietilenoglicóis/química , Liberação Controlada de Fármacos , Preparações Farmacêuticas , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Polímeros , Paclitaxel , Glutamatos , Portadores de Fármacos/química
5.
Eur Heart J ; 45(4): 287-305, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-37992083

RESUMO

BACKGROUND AND AIMS: Stanford type A aortic dissection (AD) is a degenerative aortic remodelling disease marked by an exceedingly high mortality without effective pharmacologic therapies. Smooth muscle cells (SMCs) lining tunica media adopt a range of states, and their transformation from contractile to synthetic phenotypes fundamentally triggers AD. However, the underlying pathomechanisms governing this population shift and subsequent AD, particularly at distinct disease temporal stages, remain elusive. METHODS: Ascending aortas from nine patients undergoing ascending aorta replacement and five individuals undergoing heart transplantation were subjected to single-cell RNA sequencing. The pathogenic targets governing the phenotypic switch of SMCs were identified by trajectory inference, functional scoring, single-cell regulatory network inference and clustering, regulon, and interactome analyses and confirmed using human ascending aortas, primary SMCs, and a ß-aminopropionitrile monofumarate-induced AD model. RESULTS: The transcriptional profiles of 93 397 cells revealed a dynamic temporal-specific phenotypic transition and marked elevation of the activator protein-1 (AP-1) complex, actively enabling synthetic SMC expansion. Mechanistically, tumour necrosis factor signalling enhanced AP-1 transcriptional activity by dampening mitochondrial oxidative phosphorylation (OXPHOS). Targeting this axis with the OXPHOS enhancer coenzyme Q10 or AP-1-specific inhibitor T-5224 impedes phenotypic transition and aortic degeneration while improving survival by 42.88% (58.3%-83.3% for coenzyme Q10 treatment), 150.15% (33.3%-83.3% for 2-week T-5224), and 175.38% (33.3%-91.7% for 3-week T-5224) in the ß-aminopropionitrile monofumarate-induced AD model. CONCLUSIONS: This cross-sectional compendium of cellular atlas of human ascending aortas during AD progression provides previously unappreciated insights into a transcriptional programme permitting aortic degeneration, highlighting a translational proof of concept for an anti-remodelling intervention as an attractive strategy to manage temporal-specific AD by modulating the tumour necrosis factor-OXPHOS-AP-1 axis.


Assuntos
Doenças da Aorta , Dissecção Aórtica , Benzofenonas , Isoxazóis , Doenças Vasculares , Humanos , Fator de Transcrição AP-1 , Aminopropionitrilo , Estudos Transversais , Dissecção Aórtica/genética , Doenças da Aorta/patologia , Doenças Vasculares/patologia , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/fisiologia , Fatores de Necrose Tumoral
6.
Front Neurol ; 14: 1237394, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869141

RESUMO

Introduction: Laser interstitial thermal therapy (LITT) at 1064 nm is widely used to treat epilepsy and brain tumors; however, no numerical model exists that can predict the ablation region with careful in vivo validation. Methods: In this study, we proposed a model with a system of finite element methods simulating heat transfer inside the brain tissue, radiative transfer from the applicator into the brain tissue, and a model for tissue damage. Results: To speed up the computation for practical applications, we also validated P1-approximation as an efficient and fast method for calculating radiative transfer by comparing it with Monte Carlo simulation. Finally, we validated the proposed numerical model in vivo on six healthy canines and eight human patients with epilepsy and found strong agreement between the predicted temperature profile and ablation area and the magnetic resonance imaging-measured results. Discussion: Our results demonstrate the feasibility and reliability of the model in predicting the ablation area of 1,064 nm LITT, which is important for presurgical planning when using LITT.

7.
Eur J Cardiothorac Surg ; 64(6)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37758246

RESUMO

OBJECTIVES: The aim of this study was to investigate the early and long-term outcomes after total arch replacement (TAR) and frozen elephant trunk (FET) implantation in adult patients ≤30 years with acute type A aortic dissection (ATAAD). METHODS: All young adult patients (≤30 years) with ATAAD who underwent TAR and FET between 2009 and 2017 were enrolled. The end points were major organ morbidity and mortality, aortic-related events and reoperation. RESULTS: The mean age of all 83 patients was 25.9 (standard deviation, 3.3) years. The in-hospital mortality was 9.64% (8/83), and 9 (10.8%) patients required re-exploration for bleeding. The aortic-related events risk was 42.7% (32/75) and the aortic reoperation risk was 17.3% (13/75). Overall survival was 85.5% [95% confidence interval (CI), 75.9-91.5%] at 5 years and 75.9% (95% CI, 63.3-84.7%) at 10 years. The cumulative incidence of aortic-related events was 35% (95% CI, 24-47%) at 5 years and 58% (95% CI, 36-75%) at 10 years; the cumulative reoperation rate was 15% (95% CI, 7.9-24%) at 5 years and 17% (95% CI, 9.2-27%) at 10 years. Marfan syndrome significantly increased the aortic-related events (P = 0.036) and reoperation (P = 0.041) risks. CONCLUSIONS: Despite extensive repair in young ATAAD patients, the late aortic dilatation and reoperation risk remain high. The TAR and FET procedures achieved satisfactory early outcomes and reduced late aortic dilatation and reoperation in young patients compared with other records. Close follow-up and aggressive early reintervention are essential for patients with aortic-related risk factors early in life.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Adulto Jovem , Pré-Escolar , Adulto , Implante de Prótese Vascular/métodos , Resultado do Tratamento , Estudos Retrospectivos , Fatores de Tempo , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Aorta Torácica/cirurgia
8.
J Cancer Res Ther ; 19(4): 1024-1030, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37675732

RESUMO

Background: Accurate staging of prostate cancer (PCa) is the basis for the risk stratification to select targeted treatment. Therefore, this study aimed to compare the diagnostic accuracy rates of magnetic resonance imaging (MRI) and digital rectal examination (DRE) for preoperative T staging of potentially resectable PCa. Methods: From March 2021 to March 2022, patients with PCa with T staging by prostate biopsy were included. All examinations used postoperative histopathologic T staging as the reference standard. All patients underwent DRE and MRI before the puncture. Two blinded urologists and radiologists independently evaluated DRE and MRI, respectively. Before the examination, patients were then divided into early- (T1, T2) and late-(T3, T4) stage cancer. Analysis of a paired sample sign test was performed to determine differences between DRE and MRI. Results: A total of 136 study participants with PCa were evaluated histopathologically, of whom 71% (97/136) and 29% (39/136) were at the early- and late-stage cancer, respectively. MRI had a significantly higher accuracy (91.9% vs. 76.5%, P < 0.001) compared with DRE. Further, MRI showed a higher sensitivity than DRE to diagnose early PCa (92.8% vs. 74.2%; P < 0.001). However, the specificity was not significantly different between them (89.7% vs. 82.1%; P = 0.375). Area under the curve (receiver operating curve) values were calculated as 0.78 ± 0.038 (95% confidence interval [CI], 0.71-0.86), 0.91 ± 0.028 (95% CI, 0.86-0.97), and 0.872 ± 0.028 (95% CI, 0.80-0.92) for DRE-, MRI-, MRI + DRE-based PCa predictions, respectively. The prediction performance of MRI was better than that of DRE (DeLong test, z = 3.632, P = 0.0003) and MRI + DRE (DeLong test, z = 3.715, P = 0.0002). Conclusion: For resectable PCa, the diagnostic potential of MRI in assessing the T stage was higher than that of DRE. However, DRE is still valuable, especially for patients with locally advanced PCa.


Assuntos
Exame Retal Digital , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Biópsia , Imageamento por Ressonância Magnética , Punções
9.
Epilepsy Behav ; 145: 109344, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37459719

RESUMO

BACKGROUND AND PURPOSE: In light of the ongoing COVID-19 pandemic, vaccination has emerged as the primary and most effective solution. The aim of this study was to examine compliance rates of vaccination and explore the factors that predict vaccine uptake among patients with epilepsy (PWE) who have undergone resection surgery. METHOD: To examine the variations in vaccination coverage, safety concerns, and factors influencing vaccination hesitancy among PWE who have undergone resection surgery, this study recruited patients with at least one-year follow-up. We utilized questionnaires to gather clinical characteristics and obtain information regarding COVID-19 vaccines. RESULTS: Among the 303 patients included in the study, a majority of 229 (75.58%) achieved a seizure-free outcome (Engel Ia). Of these patients, 178 (58.75%) received at least one dose of COVID-19 vaccine, and the vaccination rate has remained relatively consistent over the past six months. Nearly 94.95% of those who received the vaccine completed the full vaccination regimen, with the majority (n = 174, 97.75%) opting for an inactivated vaccine. Only three patients reported side effects unrelated to epilepsy, and one patient experienced a worsening of typical aura seizures within one month after vaccination. Notably, significant positive associations were observed between COVID-19 vaccine acceptance and adulthood (age 18 years or older) (OR = 1.820, 95% CI = 1.018-3.252, p = 0.043) as well as achieving a seizure-free outcome (OR = 2.823, 95% CI = 1.619-4.921, p < 0.001). Regarding the unvaccinated patients, approximately one-fifth expressed willingness to receive a future COVID-19 vaccine, while the remainder were hesitant (41.60%) or unsure (39.20%) about vaccination. These reservations mainly stemmed from concerns about the potential worsening of seizures and vaccine safety. CONCLUSIONS: Inactivated vaccines can be considered safe for individuals with epilepsy who have undergone resection surgery. The likelihood of being vaccinated was found to be comparatively higher among the cohort with seizure-free status or adults. To promote COVID-19 vaccination among children, it is crucial to implement comprehensive education and public awareness campaigns that emphasize the safety of vaccines. These efforts will help encourage widespread acceptance of vaccination and ensure the well-being of individuals with epilepsy.


Assuntos
COVID-19 , Epilepsias Parciais , Adolescente , Adulto , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Pandemias , Prevalência , Convulsões , Vacinação/efeitos adversos
10.
Front Cardiovasc Med ; 10: 1186181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37448791

RESUMO

Objective: The aortic root is the most frequent segment involved in Marfan syndrome. However, Marfan syndrome is a systemic hereditary connective tissue disorder, and knowledge regarding the outcomes of the native distal aorta after prophylactic aortic root surgery is limited. Methods: From April 2010 to December 2020, 226 patients with Marfan syndrome and 1,200 patients without Marfan syndrome who underwent Bentall procedures were included in this study. By propensity score matching, 134 patients were assigned to each group. Clinical manifestations and follow-up data were acquired from hospital records and telephone contact. The cumulative incidence of aortic events was estimated in Marfan and non-Marfan patients with death as a competing risk. Results: Patients with and without Marfan syndrome had similar baseline characteristics after propensity score matching. Differences in the aortic root (62.25 ± 11.96 vs. 54.03 ± 13.76, P < .001) and ascending aorta (37.71 ± 9.86 vs. 48.16 ± 16.01, P < .001) remained after matching. No difference was observed in the frequency of aortic adverse events between the two groups (10.5% vs. 4.6%, P = 0.106). The cumulative incidence of aortic events was not different between Marfan and non-Marfan patients (15.03% ± 4.72% vs. 4.18% ± 2.06%, P = 0.147). Multivariate Cox regression indicated no significant impact of Marfan syndrome on distal aortic events (HR: 1.172, 95% CI: 0.263-5.230, P = 0.835). Descending and abdominal aortic diameter above normal at the initial procedure were associated with the risk of distal aortic events (HR: 20.735, P = .003, HR: 22.981, P = .002, respectively). Conclusions: New-onset events of the residual aorta in patients undergoing Bentall procedures between the Marfan and non-Marfan groups were not significantly different. Distal aortic diameter above normal at initial surgery was associated with a higher risk of adverse aortic events.

11.
BMJ Open ; 13(6): e067469, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286325

RESUMO

INTRODUCTION: Acute aortic syndrome (AAS) is a group of acute and critical conditions, including acute aortic dissection (AAD), acute intramural haematoma and penetrating aortic ulcer. High mortality and morbidity rates result in a poor patient prognosis. Prompt diagnoses and timely interventions are paramount for saving patients' lives. In recent years, risk models for AAD have been established worldwide; however, a risk evaluation system for AAS is still lacking in China. Therefore, this study aims to develop an early warning and risk scoring system in combination with the novel potential biomarker soluble ST2 (sST2) for AAS. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit patients diagnosed with AAS at three tertiary referral centres from 1 January 2020 to 31 December 2023. We will analyse the discrepancies in sST2 levels in patients with different AAS types and explore the accuracy of sST2 in distinguishing between them. We will also incorporate potential risk factors and sST2 into a logistic regression model to establish a logistic risk scoring system for predicting postoperative death and prolonged intensive care unit stay in patients with AAS. ETHICS AND DISSEMINATION: This study was registered on the Chinese Clinical Trial Registry website (http://www. chictr. org. cn/). Ethical approval was obtained from the human research ethics committees of Beijing Anzhen Hospital (KS2019016). The ethics review board of each participating hospital agreed to participate. The final risk prediction model will be published in an appropriate journal and disseminated as a mobile application for clinical use. Approval and anonymised data will be shared. TRIAL REGISTRATION NUMBER: ChiCTR1900027763.


Assuntos
Síndrome Aórtica Aguda , Dissecção Aórtica , Humanos , Estudos Prospectivos , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/cirurgia , Biomarcadores , China/epidemiologia , Estudos Observacionais como Assunto , Estudos Multicêntricos como Assunto
12.
Arterioscler Thromb Vasc Biol ; 43(6): e172-e189, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37128913

RESUMO

BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear. METHODS: Serum uric acid levels were detected in different TAAD mouse models and patients. The urate-lowering drug allopurinol was administered in the drinking water of TAAD mice. Adenine diet-induced mice were established to investigate the role of hyperuricemia in TAAD formation and RNA-sequencing of thoracic aortas from these mice was performed. RESULTS: We found serum uric acid levels were elevated in various mouse TAAD models, including mice fed a ß-aminopropionitrile diet, Marfan mice with fibrillin-1 haploinsufficiency (Fbn1C1041G/+), and ApoE-/- mice infused with Ang II (angiotensin II), as well as in patients with TAAD. Administration of urate-lowering drug allopurinol in the drinking water significantly alleviated TAAD formation in ß-aminopropionitrile-treated mice, Fbn1C1041G/+ mice, and Ang II-infused ApoE-/- mice. Moreover, an adenine diet was used to induce hyperuricemia in mice. Intriguingly, a 4-week adenine diet feeding directly induced TAAD formation characterized by increased maximal thoracic aortic diameters and severe elastin degradation, which were ameliorated by allopurinol. Unbiased RNA-sequencing in mouse thoracic aortas suggested that FcγR (Fc gamma receptor) was upregulated upon adenine diet, but reciprocally repressed by allopurinol. Mechanistically, hyperuricemia activated FcγR-mediated ERK1/2 (extracellular signal-regulated kinase 1/2) phosphorylation to induce macrophage inflammation and TAAD development, which was abrogated by allopurinol or FcγR deficiency. CONCLUSIONS: This study uncovered an important and previously unrecognized role of hyperuricemia in mediating the pathogenesis of TAAD, and uric acid-lowering drug may represent a promising therapeutic approach for TAAD.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Água Potável , Hiperuricemia , Camundongos , Animais , Ácido Úrico , Aminopropionitrilo/efeitos adversos , Alopurinol/efeitos adversos , Água Potável/efeitos adversos , Hiperuricemia/induzido quimicamente , Hiperuricemia/tratamento farmacológico , Receptores de IgG , Transdução de Sinais , Aneurisma da Aorta Torácica/induzido quimicamente , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/prevenção & controle , Dissecção Aórtica/induzido quimicamente , Dissecção Aórtica/genética , Dissecção Aórtica/prevenção & controle , RNA , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
13.
Front Cardiovasc Med ; 10: 1093024, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37008328

RESUMO

Background: Aortic regurgitation (AR) related to Behcet's disease (BD) is rare, but usually fatal. Perivalvular leakage (PVL) is high if AR related to BD treated with regular AVR. In this study, we report the surgical management of AR secondary to BD. Methods: Between September 2017 and April 2022, 38 patients with AR secondary to Behcet's disease had surgery in our center. 17 patients did not have a BD diagnosis before surgery, 2 of them were diagnosed during surgery and received Bentall procedure. The remaining 15 patients received conventional AVR. 21 patients were diagnosed as BD before surgery, all of them received modified Bentall procedures. All patients were followed up by regular outpatient visits, transthoracic echocardiogram and CT angiography were performed to evaluate the aorta and aortic valve. Results: Seventeen patients did not have a BD diagnosis at the time of surgery. Out of them, 15 patients received conventional AVR, and a total of 13 patients suffered PVL after surgery. Twenty-one patients had a BD diagnosis before surgery. They received modified Bentall procedures and IST and steroids were given both pre- and post-surgery. In this group treated with Bentall procedure no patient suffered PVL during follow up. Conclusions: PVL is a complex scenario after conventional AVR for AR in BD. Modified Bentall procedure seems superior to isolated AVR in these cases. The use of IST and steroids before and after surgery in combination with modified Bentall procedure could have a role in effectively reducing PVL.

14.
Interact J Med Res ; 12: e45898, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36951893

RESUMO

BACKGROUND: The presence of a high left ventricular end-diastolic diameter (LVEDD) has been linked to a less favorable outcome in patients undergoing coronary artery bypass grafting (CABG) procedures. However, by taking into consideration the reference of left ventricular size and volume measurements relative to the patient's body surface area (BSA), it has been suggested that the accuracy of the predicting outcomes may be improved. OBJECTIVE: We propose that BSA weighted LVEDD (bLVEDD) is a more accurate predictor of outcomes in patients undergoing CABG compared to simply using LVEDD alone. METHODS: This study was a comprehensive retrospective cohort study that was conducted across multiple medical centers. The inclusion criteria for this study were patients who were admitted for treatment between October 2016 and May 2021. Only elective surgery patients were included in the study, while those undergoing emergency surgery were not considered. All participants in the study received standard care, and their clinical data were collected through the institutional registry in accordance with the guidelines set forth by the Society of Thoracic Surgeons National Adult Cardiac Database. bLVEDD was defined as LVEDD divided by BSA. The primary outcome was in-hospital all-cause mortality (30 days), and the secondary outcomes were postoperative severe adverse events, including use of extracorporeal membrane oxygenation, multiorgan failure, use of intra-aortic balloon pump, postoperative stroke, and postoperative myocardial infarction. RESULTS: In total, 9474 patients from 5 centers under the Chinese Cardiac Surgery Registry were eligible for analysis. We found that a high LVEDD was a negative factor for male patients' mortality (odds ratio 1.44, P<.001) and secondary outcomes. For female patients, LVEDD was associated with secondary outcomes but did not reach statistical differences for morality. bLVEDD showed a strong association with postsurgery mortality (odds ratio 2.70, P<.001), and secondary outcomes changed in parallel with bLVEDD in male patients. However, bLVEDD did not reach statistical differences when fitting either mortality or severer outcomes in female patients. In male patients, the categorical bLVEDD showed high power to predict mortality (area under the curve [AUC] 0.71, P<.001) while BSA (AUC 0.62) and LVEDD (AUC 0.64) both contributed to the risk of mortality but were not as significant as bLVEDD (P<.001). CONCLUSIONS: bLVEDD is an important predictor for male mortality in CABG, removing the bias of BSA and showing a strong capability to accurately predict mortality outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02400125; https://clinicaltrials.gov/ct2/show/NCT02400125.

15.
J Clin Med ; 12(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36836115

RESUMO

There are relatively few articles on the relationship between serum albumin and acute kidney injury (AKI). Therefore, the objective of this research was to study the relationship between serum albumin and AKI in patients who were undergoing surgery for acute type A aortic dissection. METHODS: We retrospectively collected data from 624 patients attending a Chinese hospital between January 2015 and June 2017. The target independent variable was serum albumin measured before surgery after hospital admission, and the dependent variable was AKI, defined in accordance with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: The mean age of these 624 selected patients was 48.5 ± 11.1 years, and almost 73.7% were male. A nonlinear association was detected between serum albumin and AKI; the turning point was 32 g/L. The risk of AKI decreased gradually as the serum albumin level increased up to 32 g/L (adjusted OR = 0.87; 95% CI 0.82-0.92; p < 0.001). When the serum albumin level exceeded 32 g/L, the level of serum albumin was not associated with the risk of AKI (OR = 1.01, 95% CI 0.94-1.08; p = 0.769). CONCLUSIONS: The findings suggest that preoperative serum albumin below 32 g/L was an independent risk factor for AKI in patients undergoing surgery for acute type A aortic dissection. TRIAL REGISTRATION: A retrospective cohort study.

16.
Cell Biosci ; 13(1): 38, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36814338

RESUMO

OBJECTIVE: This study aimed to identify potential biomarkers for prostate cancer (PCa) progression and metastasis, and to discern their biological functions. METHODS: Bioinformatics methods were used to screen for hub genes. The expression level of key hub genes in PCa was determined and their prognostic significance was examined. A series of functional assays were performed to investigate the function of the highest-ranking hub gene. RESULTS: Actin related protein 2/3 complex subunit 1A (ARPC1A) was identified as the hub gene. ARPC1A was highly expressed in PCa tissues and cell lines, and was an independent prognostic factor for predicting biochemical recurrence after radical prostatectomy and overall survival of PCa patients. Knockdown of ARPC1A inhibited PCa cell migration, invasion and cytoskeleton formation, but had no impact on cell proliferation and cell cycle progression. In vivo, ARPC1A overexpression promoted lung metastasis of PCa, but had no efffect on tumor growth. Additionally, glutamine metabolism was identified as an upstream regulator of ARPC1A, and promoted migration, invasion and cytoskeletal changes of PCa cell through ARPC1A. CONCLUSION: These findings suggested that ARPC1A, which correlates with poor prognosis in PCa, functions downstream of glutamine metabolism to regulate cytoskeletal changes, cellular migration and cellular invasion in this disease.

17.
Clin Chim Acta ; 541: 117232, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36690242

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication after Type A aortic dissection (TAAD) surgery, and it is associated with poor outcomes. The nephrotoxic effect of myoglobin was established, but its correlation with AKI following TAAD repair still lacks sufficient evidence. We clarified the correlation between preoperative serum myoglobin (pre-sMyo) concentrations and AKI after TAAD surgery. METHOD: A retrospective analysis was performed on the perioperative data of 382 patients treated with TAAD surgery at Beijing Anzhen Hospital. AKI was defined and classified according to the criteria established by the Kidney Disease: Improving Global Outcomes Acute Kidney Injury Work Group. We attempted to determine the correlation between pre-sMyo concentrations and postoperative AKI. RESULTS: The incidences of Stage 1, 2, and 3 AKI were 37.3 % (57/153), 23.5 % (36/153), and 39.2 % (60/153), respectively. The pre-sMyo concentrations of the AKI group were significantly increased than the non-AKI group [43.1 (21.4, 107.5) vs 26.4 (18.0, 37.2), P < 0.001]. Pre-sMyo concentrations have a linear correlation with preoperative renal function-related indicators. The multivariable logistic regression analysis showed that Ln (pre-sMyo) was an independent risk factor for AKI. When the pre-sMyo concentration was at the fourth quartile [109.3 (64.8, 213.4) ng/ml], the risk of developing any-stage and severe AKI was significantly increased (OR = 4.333, 95 % CI: 2.364-7.943, P < 0.001; OR = 3.862, 95 %, CI: 2.011-7.419, P < 0.001). This difference persisted after adjustment (OR = 3.830, 95 % CI: 1.848-7.936, P < 0.001; OR = 2.330, 95 % CI: 1.045-5.199, P = 0.039). Furthermore, pre-sMyo concentrations were not affected by lower limb malperfusion, myocardial malperfusion, and cardiac tamponade. CONCLUSIONS: Increased pre-sMyo concentrations correlated with postoperative AKI in TAAD, which may increase the risk of developing any-stage AKI and severe AKI after TAAD surgery.


Assuntos
Injúria Renal Aguda , Dissecção Aórtica , Humanos , Estudos Retrospectivos , Mioglobina , Complicações Pós-Operatórias , Fatores de Risco , Injúria Renal Aguda/etiologia
18.
J Neurosurg ; 139(1): 238-247, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36681967

RESUMO

OBJECTIVE: The authors investigated alterations in functional connectivity (FC) and EEG power during ictal onset patterns of low-voltage fast activity (LVFA) in drug-resistant focal epilepsy. They hypothesized that such changes would be useful to classify epilepsy surgical outcomes. METHODS: In a cohort of 79 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation as well as resective surgery, FC changes during the peri-LVFA period were measured using nonlinear regression (h2) and power spectral properties within/between three regions: the seizure onset zone (SOZ), early propagation zone (PZ), and noninvolved zone (NIZ). Desynchronization and power desynchronization h2 indices were calculated to assess the degree of EEG desynchronization during LVFA. Multivariate logistic regression was employed to control for confounding factors. Finally, receiver operating characteristic curves were generated to evaluate the performance of desynchronization indices in predicting surgical outcome. RESULTS: Fifty-three patients showed ictal LVFA and distinct zones of the SOZ, PZ, and NIZ. Among them, 39 patients (73.6%) achieved seizure freedom by the final follow-up. EEG desynchronization, measured by h2 analysis, was found in the seizure-free group during LVFA: FC decreased within the SOZ and between regions compared with the pre-LVFA and post-LVFA periods. In contrast, the non-seizure-free group showed no prominent EEG desynchronization. The h2 desynchronization index, but not the power desynchronization index, enabled classification of seizure-free versus non-seizure-free patients after resective surgery. CONCLUSIONS: EEG desynchronization during the peri-LVFA period, measured by within-zone and between-zone h2 analysis, may be helpful for identifying patients with favorable postsurgical outcomes and also may potentially improve epileptogenic zone identification in the future.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Humanos , Eletroencefalografia , Epilepsias Parciais/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Resultado do Tratamento
20.
Int J Radiat Oncol Biol Phys ; 116(3): 666-675, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36586494

RESUMO

PURPOSE: The purpose of this study was to explore the semantic computed tomography (CT) features associated with BRCA1-associated protein 1 (BAP1) and/or tumor protein p53 (TP53) mutation in clear cell renal cell carcinoma (ccRCC). METHODS AND MATERIALS: Clinical characteristics and gene mutation information of 336 ccRCC patients were retrieved from The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma database (TCGA-KIRC). Kaplan-Meier analysis was performed to examine prognosis by gene mutation. The CT imaging data and gene mutation information of 156 ccRCC patients treated between January 2019 and January 2021 (the training cohort) were retrospectively analyzed. The CT imaging information and gene mutation data of 123 patients with ccRCC were downloaded from The Cancer Imaging Archive and The Cancer Genome Atlas database (the external validation cohort). Univariate Chi-square test and multivariate binary logistic regression analysis were performed to determine predictors of gene mutation; a nomogram was developed using these predictors. Receiver operating characteristic curve analysis and the Hosmer-Lemeshow test were performed to evaluate the performance of the nomogram. RESULTS: Kaplan-Meier analysis showed that BAP1 and/or TP53 mutation was significantly correlated with worse survival outcome. Multivariate binary logistic regression analysis indicated ill-defined margin (P = .001), spiculated margin (P = .018), renal vein invasion (P = .002), and renal pelvis invasion (P = .001) were independent predictors of BAP1 and/or TP53 mutation. A nomogram containing these 4 semantic CT features was constructed; the area under the receiver operating characteristic curves was 0.872 (95% CI, 0.809-0.920). The Hosmer-Lemeshow test showed acceptable goodness-of-fit for the nomogram (X2 = 1.194, P = .742). The nomogram was validated in the validation cohort; it showed good accuracy (area under the receiving operating characteristic curve = 0.819, 95% CI, 0.740-0.883) and was well calibrated (X2 = 3.934, P = .559). CONCLUSIONS: Semantic CT features are a potential and promising method for predicting BAP1 and/or TP53 mutation status in ccRCC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/genética , Estudos Retrospectivos , Genes p53 , Semântica , Tomografia Computadorizada por Raios X/métodos , Mutação , Proteína BRCA1/genética
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