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1.
Ann Vasc Surg ; 74: 220-228, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33508451

RESUMO

BACKGROUND: Stanford type-B aortic dissection (TBAD) is commonly treated by thoracic endovascular aortic repair (TEVAR). Usually, the implanted stent-grafts will not cover the entire dissection-affected region for those patients with dissection extending beyond the thoracic aorta, thus the fate of the uncovered aortic segment is uncertain. This study used 3-dimensional measurement of aortic morphological changes to classify the different remodeling effects of TBAD patients after TEVAR, and hypothesized that not only initial morphological features, but also their change over time at follow-up are associated with the remodeling. METHODS: Forty-one TBAD patients underwent TEVAR and CT-angiography before and after the intervention (twice or more follow-ups) were included in this study. According to the false-lumen volume variations post-TEVAR, patients who had abdominal aortic expansion at the second follow-up were classified into the Enlarged (n =12, 29%) and remaining into the Stable group (n = 29, 71%). 3D morphological parameters were extracted on precise reconstruction of imaging datasets. Statistical differences in 3D morphological parameters over time between the 2 groups and the relationship among these parameters were analyzed. RESULTS: In the Enlarged group, the number of all tears before TEVAR was significantly higher (P = 0.022), and the size of all tears at the first and second follow-up post-TEVAR were significantly higher than that in the Stable group (P = 0.008 and P = 0.007). The location of the primary tear was significantly higher (P = 0.031) in the Stable group. The cross-sectional analysis of several slices below the primary tear before TEVAR shows different shape features of the false lumen in the Stable (cone-like) and Enlarged (hourglass-like) groups. The number of tears before TEVAR has a positive correlation with the post-TEVAR development of dissection (r = 0.683, P = 0.00). CONCLUSION: The results in this study indicated that the TBAD patients with larger tear areas, more re-entry tears and with the primary tear proximal to the arch would face a higher risk of negative remodeling after TEVAR.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Aortografia , Implante de Prótese Vascular , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares , Imageamento Tridimensional , Adulto , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/fisiopatologia , Aorta Abdominal/fisiopatologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Dilatação Patológica , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Remodelação Vascular
2.
Cell Physiol Biochem ; 51(6): 2843-2857, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30562762

RESUMO

BACKGROUND/AIMS: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. METHODS: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. RESULTS: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. CONCLUSION: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation.


Assuntos
Cílios/fisiologia , Dineínas/metabolismo , Microtúbulos/metabolismo , Animais , Cílios/ultraestrutura , Simulação por Computador , Dineínas/ultraestrutura , Módulo de Elasticidade , Desenvolvimento Embrionário , Camundongos Endogâmicos ICR , Microtúbulos/ultraestrutura , Modelos Biológicos , Movimento
3.
Ann Vasc Surg ; 45: 117-126, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28689953

RESUMO

BACKGROUND: The aim of this study is to assess the significance of the angle between superior mesenteric artery (SMA) and distal aorta in spontaneous isolated superior mesenteric artery dissection (SISMAD) by clinical and biomechanical analyses. METHODS: Thirty-seven patients with SISMAD (1 asymptomatic) and 148 controls (1:4 matched for age [mean 50.2 years], gender [92% male], and body mass index, and being ruled out for arterial disease) underwent aortic computed tomography angiography. SMA-distal aorta angle, measured on sagittal plane, was compared along with baseline characteristics (body mass index, smoking history, and comorbidities) between groups, and assessed as tool to evaluate SISMAD risk after stratification into 4 angle-interval categories. Flow analysis and fluid-structure interaction study were conducted based on patient-specific models with ultrasound-measured boundary conditions to further reveal the flow pattern and loading distribution in the 4 angle-interval categories. RESULTS: SISMAD patients versus controls had larger mean SMA-distal aorta angle (73 ± 19.8° vs. 50 ± 18.81°, P < 0.001), and more frequently smoking history (62% vs. 40%, P = 0.02) and hypertension (59% vs. 34%, P < 0.001), all multivariate predictors of no SISMAD (odds ratio 0.946 [95% confidence interval 0.927-0.966]; 0.415 [0.198-0.87]; and 0.252 [0.117-0.544], respectively). Odds ratio for SISMAD increased with increasing SMA-distal aorta angle (1, 10, 57, and 73 for <50°, 50-69°, 70-90°, and >90°, respectively; P < 0.05 for >70°). In silico study confirmed that larger angle is associated with higher stress in the arterial wall and higher oscillatory shear index in the vessel lumen at the SMA superior convex, where dissection commonly occurs. CONCLUSIONS: Besides smoking history and hypertension, SISMAD was positively associated with a morphological parameter, the SMA-distal aorta angle. This might be due to the greater wall stress and oscillatory stress index in the arterial convex with a larger angle.


Assuntos
Aorta/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Artéria Mesentérica Superior/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Pontos de Referência Anatômicos , Dissecção Aórtica/etiologia , Dissecção Aórtica/fisiopatologia , Aorta/fisiopatologia , Fenômenos Biomecânicos , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Modelos Logísticos , Masculino , Artéria Mesentérica Superior/fisiopatologia , Pessoa de Meia-Idade , Modelos Cardiovasculares , Análise Multivariada , Razão de Chances , Modelagem Computacional Específica para o Paciente , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Fatores de Risco , Fumar/efeitos adversos , Estresse Mecânico
4.
Breast Cancer Res ; 16(4): 408, 2014 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-25056574

RESUMO

INTRODUCTION: We investigated Nestin expression in triple-negative breast cancer and examined how the modulation of Nestin expression affects cell cycle progression, survival, invasion and regulatory signaling in breast cancer stem cells (CSC) in vitro. METHODS: Nestin expression in 150 triple-negative breast cancer specimens were examined by immunohistochemistry. The role of Nestin expression in tumorigenesis was examined by assaying naturally occurring Nestinhigh/Nestinlow CSC from 12 breast cancer tissues, as well as CSC from 26 clinical specimens, where Nestin overexpression and silencing was achieved by genetic manipulation, for their ability to form mammospheres and induce solid tumors. Cell cycle progression, spontaneous apoptosis and invasiveness of Nestin-silenced breast CSC were investigated by flow cytometry and transwell assays. The relative levels of expression of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathway-related molecules were determined by western blotting. RESULTS: Nestin expression was significantly associated with poor survival in patients with triple-negative breast cancer (P = 0.01). Nestinhigh breast CSC rapidly formed typical mammospheres in vitro. Nestinhigh, but not Nestinlow CSC, efficiently formed solid tumors in vivo. Nestin silencing induced cell cycle arrest at G2/M (52.03% versus 19.99% in controls) and promoted apoptosis (36.45% versus 8.29% in controls). Nestin silencing also inhibited breast CSC invasiveness, and was associated with significantly upregulated E-cadherin, while N-cadherin, vimentin, a-smooth muscle actin (a-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression was downregulated (P <0.05 for all). Nestin silencing also upregulated Axin, glycogen synthase kinase-3 beta (GSK-3ß), adenomatous polyposis coli (APC), and peroxisome proliferator-activated receptor alpha (PPARa), and downregulated ß-catenin, c-Myc, cyclin D and MMP-7 expression in CSC. Inhibition of the Wnt/ß-catenin pathway mitigated mammosphere formation in Nestinhigh CSC, while inhibition of GSK-3ß promoted the mammosphere formation in Nestinlow CSC (P <0.05 for all). CONCLUSIONS: Our data indicates that Nestin positively regulates the proliferation, survival and invasiveness of breast CSC by enhancing Wnt/ß-catenin activation.


Assuntos
Neoplasias da Mama/metabolismo , Células-Tronco Neoplásicas/metabolismo , Nestina/metabolismo , Via de Sinalização Wnt , Animais , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Sobrevivência Celular/genética , Transformação Celular Neoplásica/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/genética , Feminino , Inativação Gênica , Xenoenxertos , Humanos , Nestina/genética , Prognóstico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
5.
Tumour Biol ; 35(3): 1827-31, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24363083

RESUMO

The objective of this study was to investigate the expression and significance of the GRHL3 protein in breast cancer diagnosis and prognosis. Overall, 111 patients with histologically confirmed breast cancer who had undergone radical surgery were enrolled in this study. The GRHL3 protein expression status in the breast cancers was evaluated by immunohistochemistry. The relationship between GRHL3 protein expression status and clinicopathological factors and the breast cancer prognoses was also determined. In total, 71 (63.96%) out of 111 cases were found to express GRHL3 protein. GRHL3 expression was higher in breast cancers, compared to other pathologic cancer types (χ (2) = 5.68, P < 0.05). Moreover, GRHL3 protein was also observed to correlate with breast cancer clinical stage and histological grade (χ (2) = 7.99, P < 0.05 and χ (2) = 7.907, P < 0.05, respectively). Interestingly, triple-negative breast cancers had lower expression rates than other breast cancers (41.18 vs. 71.28%, P < 0.05). GRHL3 was shown to be an independent prognostic factor of breast cancer in Cox regression analysis. Altogether, our results indicate predominant GRHL3 expression in breast cancers, especially non-triple-negative cancers and early stage cancers. GRHL3 expression appeared to decrease with tumor progression. Survival analysis demonstrated the inhibitory effect of GRHL3 in breast cancer. These results strongly suggest the possible involvement of GRHL3 in tumor suppression.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Proteínas de Ligação a DNA/biossíntese , Fatores de Transcrição/biossíntese , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Proteínas de Ligação a DNA/análise , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Transcrição/análise
6.
Tumour Biol ; 35(3): 1751-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24443256

RESUMO

The purpose of this study is to investigate the relationship between nestin expression and clinicopathological characteristics, immunohistochemical markers and to determine the prognostic impact of nestin expression in breast cancer so as to lay a foundation for the treatment of breast cancer. A total of 109 patients who were histologically diagnosed with breast cancer and underwent radical operations from January 2006 to September 2007 in China Medical University were enrolled in the study. Nestin protein expression was evaluated by immunohistochemistry. The relationship between nestin and other parameters was analyzed by using chi-square test and Fisher's exact test. Nestin expression was observed in 37.6% (41/109) of cases. There were no significant differences between the age of >40 and ≤40 years group in terms of nestin expression (39.8 vs 18.2%; P = 0.161). The rate of nestin expression between those with and without lymph node metastasis was not significantly different (X (2) = 0.086; P = 0.769). The 5-year survival rates of the patients with nestin expression and those without were 34.1% (14/41) and 55.9% (38/68), respectively (P = 0.028). Overall, triple-negative breast cancers had higher expression rates than other cancers (54.1 vs 29.2%; P = 0.011). Nestin expression rate in ER- and PR-negative tumors was found to be significantly higher than cases that were ER- and PR-positive (P = 0.011 and P = 0.036, respectively). However, it was not found that HER2 expression was related to nestin expression (P = 0.120). These results suggest that the expression of nestin might play an important role in the prognosis of breast carcinoma, especially in the triple-negative subgroups.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidade , Nestina/biossíntese , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Nestina/análise , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia
7.
World J Surg Oncol ; 12: 193, 2014 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-24969079

RESUMO

BACKGROUND: Curative resection is the treatment of choice for gastric cancer, but it is unclear whether gastrectomy should also include splenectomy. We retrospectively analyzed long-term survival in patients in our hospital who underwent gastrectomy plus splenectomy (G+S) or gastrectomy alone (G-A) for gastric cancer. METHODS: We identified 214 patients who underwent surgery with curative intent between 1980 and 2003. Of these, 100 underwent G+S, and 114 underwent G-A. The primary endpoint was 5-year overall survival (OS). RESULTS: Median follow-up was 18 months in patients who underwent G+S, and 26.5 months in patients who underwent G-A. The 5-year OS rate was significantly higher in patients who underwent G-A (33.8%; 95% CI 24.2 to 43.4%) than in those who underwent G+S (28.8%; 95% CI 19.6 to 38.0%) (log-rank test, P=0.013). CONCLUSIONS: Splenectomy does not benefit patients undergoing gastrectomy for gastric cancer. Routine splenectomy should be abandoned in patients undergoing radical resections for gastric cancer.


Assuntos
Gastrectomia , Esplenectomia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Resultado do Tratamento
8.
Aging (Albany NY) ; 16(6): 5545-5566, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38517376

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC), with discouraging morbidity and mortality, ranks as one of the most prevalent tumors worldwide. Pyrimidine metabolism is a critical process that regulates DNA and RNA synthesis in cells. It is imperative to investigate the significance of pyrimidine metabolism in liver cancer. METHODS: Transcriptome and clinical data were downloaded from the TCGA database and the GEO database. The genes related to pyrimidine metabolism were sourced from the MSigDB. The pyrimidine metabolism-related signature (PMRS) was constructed through Cox regression and Lasso regression and then verified in the external validation set from the ICGC database. Functional enrichment, immune infiltration analysis, drug sensitivity, and Immunophenoscore (IPS) were further implemented to predict the response to immunotherapy. The role of PMRS in the malignant phenotype of hepatocellular carcinoma was explored by conducting a series of in vitro experiments. RESULTS: Our study developed a four-genes PMRS which demonstrates a substantial correlation with the prognosis of HCC patients, serving as an independent predictor in clinical practice. The result of risk-stratified analysis yielded evidence that low-risk patients experienced more favorable clinical outcomes. The nomogram exhibited remarkable prognostic predictive value. The subsequent results revealed that low-risk patients manifested a more promising response to immunotherapy. Moreover, the results of cell experiments demonstrated that the downregulation of DCK markedly inhibited the malignant phenotype of hepatocellular carcinoma. CONCLUSIONS: Our pyrimidine metabolism-centered prognostic signature accurately predicts overall survival, immune status, and treatment response in hepatocellular carcinoma (HCC) patients, offering innovative insights for precise diagnosis, personalized treatment, and improved prognosis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Prognóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Imunoterapia , Pirimidinas/uso terapêutico
9.
Cells ; 13(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38891124

RESUMO

Canine oral melanoma is the most prevalent malignant tumor in dogs and has a poor prognosis due to its high aggressiveness and high metastasis and recurrence rates. More research is needed into its treatment and to understand its pathogenic factors. In this study, we isolated a canine oral mucosal melanoma (COMM) cell line designated as COMM6605, which has now been stably passaged for more than 100 generations, with a successful monoclonal assay and a cell multiplication time of 22.2 h. G-banded karyotype analysis of the COMM6605 cell line revealed an abnormal chromosome count ranging from 45 to 74, with the identification of a double-armed chromosome as the characteristic marker chromosome of this cell line. The oral intralingual and dorsal subcutaneous implantation models of BALB/c-nu mice were successfully established; Melan-A (MLANA), S100 beta protein (S100ß), PNL2, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2) were stably expressed positively in the canine oral tumor sections, tumor cell lines, and tumor sections of tumor-bearing mice. Sublines COMM6605-Luc-EGFP and COMM6605-Cherry were established through lentiviral transfection, with COMM6605-Luc-EGFP co-expressing firefly luciferase (Luc) and enhanced green fluorescent protein (EGFP) and COMM6605-Cherry expressing the Cherry fluorescent protein gene. The COMM6605-Luc-EGFP fluorescent cell subline was injected via the tail vein and caused lung and lymph node metastasis, as detected by mouse live imaging, which can be used as an animal model to simulate the latter steps of hematogenous spread during tumor metastasis. The canine oral melanoma cell line COMM6605 and two sublines isolated and characterized in this study can offer a valuable model for studying mucosal melanoma.


Assuntos
Melanoma , Mucosa Bucal , Neoplasias Bucais , Animais , Cães , Melanoma/patologia , Melanoma/genética , Melanoma/veterinária , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/veterinária , Linhagem Celular Tumoral , Mucosa Bucal/patologia , Mucosa Bucal/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças , Camundongos Nus
10.
Aging (Albany NY) ; 15(24): 14845-14863, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38112634

RESUMO

BACKGROUND: Kinesin family member C1 (KIFC1) is an essential member of the motor protein family, which is critically involved in various cellular events, such as mitosis, meiosis, and macromolecular transport, but also in carcinogenesis, malignant progression, and tumor recurrence. METHODS: The analysis determined the relationship between KIFC1 expression, prognosis significance, immune characteristics landscape, and genetic alterations in pan-cancer with the data extracted from web-based platforms and databases, including but not limited to UCSC, NCBI, GEPIA2, HPA, cBioPortal, SangerBox, UALCAN, GEO and TCGA. Additionally, the expression of KIFC1 in pancreatic cancer tumor tissues and adjacent normal tissues was evaluated through immunohistochemistry. In vitro Edu, colony formation, wound healing, and Transwell assay were done to elucidate the biological functions of KIFC1 in pancreatic cancer cells. RESULTS: The analysis revealed that KIFC1 is upregulated in most cancers, and its increased expression is significantly associated with reduced overall survival and disease-free survival in multiple cancer types. Additionally, strong correlations between KIFC1 expression and tumor immunotherapy were observed across various malignancies. Through univariate and multivariate Cox regression analyses using TCGA data, KIFC1 was identified as an independent predictor of prognosis in pancreatic cancer cases. Furthermore, cellular experiments demonstrated that knockdown of KIFC1 resulted in the suppression of cell proliferation, migration, and invasive ability. CONCLUSIONS: Our study indicated that KIFC1 harbors the potential to be a prognostic and immunotherapeutic biomarker of tumors, and it can have an impact on the metastasis and the cell cycle of pancreatic cancer cells.


Assuntos
Cinesinas , Neoplasias Pancreáticas , Humanos , Mitose , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Fenótipo , Prognóstico , Cinesinas/genética , Cinesinas/imunologia , Cinesinas/metabolismo
11.
Braz J Cardiovasc Surg ; 37(4): 439-446, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35976203

RESUMO

INTRODUCTION: A weak venous wall is one of the major reasons contributing to vein graft failure after coronary artery bypass grafting (CABG). We investigated whether adventitial collagen cross-linking by glutaraldehyde reinforces venous wall, preserving the endothelium of veins during high-pressure distention. METHODS: Human saphenous veins (SVs) were collected from 40 patients undergoing CABG, and adventitia cross-linking was performed with 0.3% glutaraldehyde for five minutes. The cross-linked SVs were accessed by biodegradation assay, immunofluorescent staining, and tensile test. Native SVs and cross-linked SVs from another 20 patients received the 200 mmHg pressure distention for two minutes. Pressure-induced injury of SVs were accessed by immunohistochemistry and electron microscopy. RESULTS: Time to digestion was 97±13 minutes for native SVs and 720±0 minutes for cross-linked SVs (P<0.05). After adventitial cross-linking, the collagen I fibres of the vein remarkably presented with compact and nonporous arrangement. In the high-stretch region (stretch ratio 1.4-1.8), the Young's elastic modulus of stress-stretch ratio curve in cross-linked SVs was larger than that in native SVs (13.88 vs. 5.83, P<0.05). The cross-linked SVs had a lower extent of endothelial denudation without fibre fracture during high-pressure distension than native SVs. Comparing with the non-cross-linked SVs, the percentage of endothelial nitric oxide synthase staining length on the endothelium of cross-linked SVs was significantly preserved after high-pressure distension (85.2% vs. 64.7%, P<0.05). CONCLUSION: Adventitial collagen cross-linking by glutaraldehyde reinforced venous wall by increasing stiffness and decreasing extensibility of SVs and mitigated the endothelial damage under high-pressure distension.


Assuntos
Túnica Adventícia , Veia Safena , Colágeno/metabolismo , Ponte de Artéria Coronária , Dilatação Patológica , Endotélio Vascular , Glutaral/farmacologia , Humanos , Veia Safena/transplante
12.
Front Bioeng Biotechnol ; 10: 831903, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433660

RESUMO

Thoracic endovascular aortic repair (TEVAR) is a common treatment for Stanford type B aortic dissection (TBAD). However, re-entry tears might be found distal to the stented region which transports blood between the true and false lumens. Sealing the re-entry tears, especially for the thoracic tears, could further reduce blood perfusion to the false lumen; however, it might also bring risks by re-intervention or surgery. Wise determination of the necessity to seal the re-entry tears is needed. In this study, patient-specific models of TBAD were reconstructed, and the modified models were established by virtually excluding the thoracic re-entries. Computational hemodynamics was investigated, and the variation of the functional index and first balance position (FBP) of the luminal pressure difference, due to the sealing of the re-entries, was reported. The results showed that the direction of the net flow through the unstented thoracic re-entries varied among cases. Excluding the re-entries with the net flow toward the false lumen may induce the FBP moving distally and the relative particle residence time increasing in the false lumen. This study preliminarily demonstrated that the hemodynamic status of the re-entry tears might serve as an indicator to the necessity of sealing. By quantifying the through-tear flow exchange and shift of FBP, one can predict the hemodynamic benefit by sealing the thoracic re-entries and thus wisely determine the necessity of further interventional management.

13.
Biomed Res Int ; 2022: 9868022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35132379

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is widely acknowledged as a malignant tumor with rapid progression, high recurrence rate, and poor prognosis. At present, there is a paucity of reliable biomarkers at the clinical level to guide the management of HCC and improve patient outcomes. Our research is aimed at assessing the prognostic value of MAD2L1 in HCC. METHODS: Four datasets, GSE121248, GSE101685, GSE85598, and GSE62232, were selected from the GEO database to analyze differentially expressed genes (DEGs) between HCC and normal liver tissues. After functional analysis, we constructed a protein-protein interaction network (PPI) for DEGs and identified core genes in this network with high connectivity with other genes. We assessed the relationship between core genes and the pathogenesis and prognosis of HCC. Finally, we explored the gene regulatory signaling mechanisms involved in HCC pathogenesis. RESULTS: 145 DEGs were screened from the intersection of the four GEO datasets. MAD2L1 was associated with most genes according to the PPI network and was selected as a candidate gene for further study. Survival analysis suggested that high MAD2L1 expression in HCC correlated with a worse prognosis. In addition, real-time quantitative PCR (RT-qPCR), western blot (WB), and immunohistochemistry (IHC) findings suggested that the expression of MAD2L1 was abnormally increased in HCC tissues and cells compared to paraneoplastic tissues and normal hepatocytes. CONCLUSION: We found that high MAD2L1 expression in HCC was significantly associated with overall patient survival and clinical features. We also explored the potential biological properties of this gene.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas Mad2/genética , Mapas de Interação de Proteínas/genética , Biomarcadores Tumorais/genética , Biologia Computacional , Bases de Dados Genéticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais , Análise de Sobrevida
14.
Comput Methods Biomech Biomed Engin ; 24(11): 1251-1262, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33522843

RESUMO

Computational hemodynamics quantifying the flow environment is an important tool in understanding aortic dissection. In this study, various inflow boundaries were applied on a patient-specific model and compared to the individualized velocimetry. The results indicated that the computations generally overestimated the flow volume and underestimated the wall shear stress. By quantifying the accuracy of the simulation results, two inflow settings were suggested. One was individualized, the PCMRI-extracted 4D flow information, and the other was averaged by healthy data, the ultrasound-extracted averaged flow waveform with parabolic velocity profile. This study might contribute to improving the precise computation of aortic dissection hemodynamics.


Assuntos
Dissecção Aórtica , Dissecção Aórtica/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Hemodinâmica , Humanos , Modelos Cardiovasculares , Ultrassonografia , Ultrassonografia Doppler
15.
J Thorac Cardiovasc Surg ; 162(2): e165-e176, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32217023

RESUMO

OBJECTIVE: In this study we aimed to propose a new computed tomography-based hemodynamic indicator to quantify the functional significance of aortic dissection and predict post intervention luminal remodeling. METHODS: Computational hemodynamics and 3D structural analyses were conducted in 51 patients with type B aortic dissection, at initial presentation and at approximately 1 month, 3 months, and 1 year post intervention. A functional index was proposed on the basis of luminal pressure difference. Statistical relationships between the proposed indicator and longitudinal luminal development were analyzed. RESULTS: The computed luminal pressure difference (true lumen pressure minus false lumen pressure) varied overall from positive to negative along the aorta. The first balance position at which the pressure difference equals 0 was proposed as the functional indicator. A more distally located first balance position indicated better functional status. Implantation of stent graft distally shifted this balance position. Patients with the balance position shifted out of the dissected region (43%) presented the highest functional improvement after intervention; whereas those with the balance position shifted to the abdominal region (25%) showed unsatisfactory results. The magnitude of distal shifting of the first balance position at 3 months post intervention was statistically related to the subsequent true lumen expansion and false lumen reduction. CONCLUSIONS: The first balance position of luminal pressure difference quantified the hemodynamic status of the dissected aorta. The magnitude of distal shifting of the balance position after intervention was associated with functional improvement and might be used predict longitudinal aortic remodeling.


Assuntos
Aneurisma Aórtico/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Aortografia , Angiografia por Tomografia Computadorizada , Hemodinâmica , Adulto , Idoso , Dissecção Aórtica/fisiopatologia , Dissecção Aórtica/cirurgia , Aneurisma Aórtico/fisiopatologia , Aneurisma Aórtico/cirurgia , Pressão Arterial , Implante de Prótese Vascular , Procedimentos Endovasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento
16.
Med Image Anal ; 69: 101931, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33618153

RESUMO

Aortic dissection (AD) is a life-threatening cardiovascular disease with a high mortality rate. The accurate and generalized 3-D reconstruction of AD from CT-angiography can effectively assist clinical procedures and surgery plans, however, is clinically unavaliable due to the lacking of efficient tools. In this study, we presented a novel multi-stage segmentation framework for type B AD to extract true lumen (TL), false lumen (FL) and all branches (BR) as different classes. Two cascaded neural networks were used to segment the aortic trunk and branches and to separate the dual lumen, respectively. An aortic straightening method was designed based on the prior vascular anatomy of AD, simplifying the curved aortic shape before the second network. The straightening-based method achieved the mean Dice scores of 0.96, 0.95 and 0.89 for TL, FL, and BR on a multi-center dataset involving 120 patients, outperforming the end-to-end multi-class methods and the multi-stage methods without straightening on the dual-lumen segmentation, even using different network architectures. Both the global volumetric features of the aorta and the local characteristics of the primary tear could be better identified and quantified based on the straightening. Comparing to previous deep learning methods dealing with AD segmentations, the proposed framework presented advantages in segmentation accuracy.


Assuntos
Dissecção Aórtica , Dissecção Aórtica/diagnóstico por imagem , Aorta , Angiografia por Tomografia Computadorizada , Humanos , Redes Neurais de Computação , Estudos Retrospectivos
17.
Int J Numer Method Biomed Eng ; 36(11): e3394, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32790046

RESUMO

PURPOSE: Pararenal abdominal aortic aneurysms (PRAAAs) are a life-threatening disease, and hemodynamic analysis may provide greater insight into the effectiveness and long-term outcomes of endovascular aneurysm repair (EVAR). However, the lack of patient-specific boundary conditions on the periphery compromises the accuracy. Windkessel (WK) boundary conditions coupled to hemodynamic follow-up models of a PRAAA patient, aims to provide insights into the link between hemodynamics and poor prognosis. METHOD: One PRAAA patient underwent EVAR and reintervention after one branch of stent-graft (SG) had migrated. Totally five computational follow-up models were studied. Patient-specific flow data acquired via ultrasound were used to define the boundary conditions in the ascending aorta and the following three branches. Coupled zero-dimensional WK models representing the distal vasculature were used to define the outlet boundary conditions under the abdomen. RESULTS: Flow divisions of the main SG branches were 40.7% and 24.7%, respectively. Time-averaged wall shear stress and oscillatory shear index (OSI) increased at the junction connected the SG branch and the stent leading to the right common iliac artery (RCIA) where the stent migrated. The OSI and relative residence time (RRT) value in superior mesenteric artery increased notably after the migration, the RRT continuously increased following the reintervention. CONCLUSION: Unbalanced flow, resulting in locally high-speed flow, high WSS and OSI might significantly affect stent stability. Results suggest that diameters and interconnection design of stents in complex cases should take the flow division into consideration and computational simulations might be considered as a tool for intervention protocol design.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma da Aorta Abdominal/cirurgia , Prótese Vascular , Hemodinâmica , Humanos , Desenho de Prótese , Stents , Resultado do Tratamento
18.
Int J Numer Method Biomed Eng ; 35(6): e3197, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30838798

RESUMO

Endovascular repair with parallel stent-grafts (SG) is a challenging technique that reconstructs the luminal flow pathways by implanting parallel-placed SGs into the vessel. After treatment, occlusion and shifting of the parallel SGs are sometimes reported, which could be fatal and difficult to be re-operated. These issues are highly related to the local hemodynamic conditions in the stented region. In this study, a patient case treated by the octopus endograft technique (a head-SG with three limb-SGs) and experienced limb-SG occlusion is studied. 3-D models are established based on computed tomography (CT) angiography datasets pretreatment and posttreatment as well as during follow-ups. Hemodynamic quantities such as pressure drop, wall shear stress-related parameters, and flow division in limb-SGs and visceral arteries are quantitatively investigated. Optimizations on the length of the head-SG and diameter of the limb-SGs are analyzed based on various scenarios. The results indicate that when reconstructing the flow pathways via octopus stenting, it is important to ensure the flow distribution as physiologically required with this new morphology. Position (or length) of the head-SG and diameter of the limb-SGs play an important role in controlling flow division, and high time average wall shear stress (TAWSS) around the head-SG acts as a main factor for graft immigration. This study, by proposing optimization suggestions with hemodynamic analyses for a specific case, implicates that pretreatment SG scenarios may assist in wise selection and placement of the device and thus may improve long-term effectiveness of this kind of challenging endovascular repair techniques.


Assuntos
Procedimentos Endovasculares , Hemodinâmica/fisiologia , Aorta/cirurgia , Angiografia por Tomografia Computadorizada , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Pressão , Estresse Mecânico , Sístole/fisiologia
19.
Theranostics ; 8(20): 5758-5771, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555579

RESUMO

In aortic endovascular repair, the prediction of stented vessel remodeling informs treatment plans and risk evaluation; however, there are no highly accurate and efficient methods to quantitatively simulate stented vessels. This study developed a fast virtual stenting algorithm to simulate stent-induced aortic remodeling to assist in real-time thoracic endovascular aortic repair planning. Methods: The virtual stenting algorithm was established based on simplex deformable mesh and mechanical contact analysis. The key parameters of the mechanical contact analysis were derived from mechanical tests on aortic tissue (n=40) and commonly used stent-grafts (n=6). Genetic algorithm was applied to select weighting parameters. Testing and validation of the algorithm were performed using pre- and post-treatment computed tomography angiography datasets of type-B aortic dissection cases (n=66). Results: The algorithm was efficient in simulating stent-induced aortic deformation (mean computing time on a single processor: 13.78±2.80s) and accurate at the morphological (curvature difference: 1.57±0.57%; cross-sectional area difference: 4.11±0.85%) and hemodynamic (similarity of wall shear stress-derived parameters: 90.16-90.94%) levels. Stent-induced wall deformation was higher (p<0.05) in distal stent-induced new entry cases than in successfully treated cases, and this deformation did not differ significantly among the different stent groups. Additionally, the high stent-induced wall deformation regions and the new-entry sites overlapped, indicating the usefulness of wall deformation to evaluate the risks of device-induced complications. Conclusion: The novel algorithm provided fast real-time and accurate predictions of stent-graft deployment with luminal deformation tracking, thereby potentially informing individualized stenting planning and improving endovascular aortic repair outcomes. Large, multicenter studies are warranted to extend the algorithm validation and determine stress-induced wall deformation cutoff values for the risk stratification of particular complications.


Assuntos
Doenças da Aorta/cirurgia , Procedimentos Endovasculares/métodos , Fenômenos Mecânicos , Modelagem Computacional Específica para o Paciente , Stents , Procedimentos Cirúrgicos Torácicos/métodos , Adulto , Idoso , Algoritmos , Angiografia , Simulação por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
20.
J Vasc Surg Cases Innov Tech ; 3(2): 90-94, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29349386

RESUMO

Surgeon-modified retrograde branched extension limb assembling technique and bridged endografts were successfully used to exclude an asymptomatic pararenal abdominal aortic aneurysm and to reconstruct the superior mesenteric artery and bilateral renal arteries in a case with high-grade celiac artery stenosis, nondilated aorta above the superior mesenteric artery, and large lumen below the renal arteries. In patient-specific models for hemodynamics analysis, enhanced flow diversion to visceral arteries up to 6-month follow-up confirmed treatment feasibility; however, endograft configurations could be improved to avoid sharp corners at bifurcations, thereby ensuring smooth flow transport and possibly reducing risk for endograft narrowing or the development of thrombosis.

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