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1.
Quant Imaging Med Surg ; 14(4): 2788-2799, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617180

RESUMO

Background: Color Doppler ultrasonography (CDUS) is feasible to detect arteriovenous fistula (AVF) dysfunction in hemodialysis patients but is not sufficient to map the structure of fistula required for interventions. This study is designed to evaluate the diagnostic accuracy of three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) at 3.0T versus CDUS for AVF dysfunction, by using digital subtraction angiography (DSA) as reference. Methods: This prospective study enrolled 68 consecutive patients with dysfunctional AVF who underwent both CDUS and TOF-MRA at Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The analysis of the dysfunctional AVFs was divided into three regions: the feeding artery, fistula and draining veins. In the whole- and per-regional-based analyses, two observers who were blinded to the clinical and DSA results independently analyzed all CDUS and TOF-MRA datasets. The image quality and stenosis severity of the lesions on TOF-MRA were evaluated. A receiver operating characteristic curve was applied to analyze the detection of AVF dysfunction with TOF-MRA. Results: A total of 204 vessel regions were evaluated. The whole-region-based image quality of TOF-MRA was poorer in patients with a total occlusion (1.8±0.8) than in those with stenosis (2.7±0.6, P<0.001). In the whole-region analyses, TOF-MRA had higher sensitivity [99.1% (94.6-100.0%) vs. 82.9% (74.6-89.0%), P<0.001] and similar specificity [93.1% (85.0-97.1%) vs. 94.3% (86.5-97.9%), P=0.755] than CDUS. The per-region-based analyses showed that TOF-MRA yielded higher sensitivity [fistula region, 98.1% (88.4-99.9%) vs. 80.8% (67.0-89.9%); P=0.004; draining vein region, 100.0% (92.5-100.0%) vs. 85.0% (72.9-2.5%); P=0.003] and similar specificity [fistula region, 88.2% (62.3-97.8%) vs. 88.2% (62.3-97.9%); P>0.99; draining vein region, 100.0% (59.8-100.0%) vs. 87.5% (46.7-99.3%); P>0.99] than CDUS. Sensitivity and specificity of TOF-MRA were comparable to those of CDUS in feeding artery region. Conclusions: TOF-MRA is a feasible and accurate method to display AVF dysfunction in hemodialysis patients, and this method might fulfill the endovascular treatment planning requirements.

2.
Adv Healthc Mater ; 13(13): e2303027, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38323853

RESUMO

Effective neuroprotective agents are required to prevent neurological damage caused by reactive oxygen species (ROS) generated by cerebral ischemia-reperfusion injury (CIRI) following an acute ischemic stroke. Herein, it is aimed to develop the neuroprotective agents of cerium oxide loaded with platinum clusters engineered modifications (Ptn-CeO2). The density functional theory calculations show that Ptn-CeO2 could effectively scavenge ROS, including hydroxyl radicals (·OH) and superoxide anions (·O2 -). In addition, Ptn-CeO2 exhibits the superoxide dismutase- and catalase-like enzyme activities, which is capable of scavenging hydrogen peroxide (H2O2). The in vitro studies show that Ptn-CeO2 could adjust the restoration of the mitochondrial metabolism to ROS homeostasis, rebalance cytokines, and feature high biocompatibility. The studies in mice CIRI demonstrate that Ptn-CeO2 could also restore cytokine levels, reduce cysteine aspartate-specific protease (cleaved Caspase 3) levels, and induce the polarization of microglia to M2-type macrophages, thus inhibiting the inflammatory responses. As a result, Ptn-CeO2 inhibits the reperfusion-induced neuronal apoptosis, relieves the infarct volume, reduces the neurological severity score, and improves cognitive function. Overall, these findings suggest that the prominent neuroprotective effect of the engineered Ptn-CeO2 has a significant neuroprotective effect and provides a potential therapeutic alternative for CIRI.


Assuntos
Cério , Fármacos Neuroprotetores , Platina , Traumatismo por Reperfusão , Cério/química , Cério/farmacologia , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Camundongos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Platina/química , Platina/farmacologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Homeostase/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Apoptose/efeitos dos fármacos
3.
Quant Imaging Med Surg ; 14(2): 1791-1802, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415115

RESUMO

Background: Carotid blowout syndrome (CBS) frequently occurs at the distal internal carotid artery (distal-ICA) in patients with nasopharyngeal carcinoma (NPC), and remedial treatments run a high risk for neurologic complications. A case-control study was conducted to evaluate the safety and efficacy of protective stent insertion at the distal-ICA to prevent CBS in NPC patients, with a comparison to endovascular coil occlusion. Methods: A total of 28 consecutive NPC patients at high risk of CBS from June 2019 to December 2021 in Shanghai Sixth People's Hospital (a tertiary institution) were retrospectively included and divided into a stent protection group and occlusion group. Technique feasibility, treatment outcomes and neurological deficiency were compared between the two groups by two-sample test. Kaplan-Meier analysis compared patients' survival rates at mid-term follow-up. Results: Stent insertion was performed in 15 patients and ICA occlusion in 13 patients. The technical success rate was 100% in both groups. Procedure-related ischemic stroke was identified in 2 patients (15.4%) in the occlusion group, compared with none in the stent protection group. Bleeding was encountered in one patient in the stent protection group and one patient in the occlusion group, each. During a median follow-up of 10.5 (range, 2-31) months, 3 patients (20%) showed asymptomatic in-stent occlusion in the stent protection group. Notably, the median survival time was significantly longer in the stent protection group than in the occlusion group (23.3 vs. 15.8 months, P=0.04). Conclusions: Protective stenting the distal-ICA was similarly effective in preventing CBS in NPC patients but was safer than endovascular occlusion of ICA.

4.
Expert Opin Drug Deliv ; 20(7): 1015-1031, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37452715

RESUMO

OBJECTIVES: Metastasis is still one of the main obstacles in the treatment of breast cancer. This study aimed to develop disulfiram (DSF) and doxorubicin (DOX) co-loaded nanoparticles (DSF-DOX NPs) with enzyme/pH dual stimuli-responsive characteristics to inhibit breast cancer metastasis. METHODS: DSF-DOX NPs were prepared using the amphiphilic poly(ε-caprolactone)-b-poly(L-glutamic acid)-g-methoxy poly(ethylene glycol) (PCL-b-PGlu-g-mPEG) copolymer by a classical dialysis method. In vitro release tests, in vitro cytotoxicity assay, and anti-metastasis studies were conducted to evaluate pH/enzyme sensitivity and therapeutic effect of DSF-DOX NPs. RESULTS: The specific pH and enzyme stimuli-responsiveness of DSF-DO NPs can be attributed to the transformation of secondary structure and the degradation of amide bonds in the PGlu segment, respectively. This accelerated drug release significantly increased the cytotoxicity to 4T1 cells. Compared with the control group, the DSF-DOX NPs showed a strong inhibition of in vitro metastasis with a wound healing rate of 36.50% and a migration rate of 18.39%. Impressively, in vivo anti-metastasis results indicated that the metastasis of 4T1 cells was almost completely suppressed by DSF-DOX NPs. CONCLUSION: DSF-DOX NPs with controllable tumor site delivery of DOX and DSF were a prospectively potential strategy for metastatic breast cancer treatment.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Nanopartículas , Humanos , Feminino , Dissulfiram/farmacologia , Dissulfiram/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Polietilenoglicóis/química , Concentração de Íons de Hidrogênio , Nanopartículas/química , Portadores de Fármacos/química , Linhagem Celular Tumoral
5.
Ann Med ; 55(1): 2200257, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37074291

RESUMO

Aim: To investigate the treatment of intractable epistaxis after radiotherapy for nasopharyngeal carcinoma (NPC).Methods: This review focuses on the anatomy and pathophysiology, mechanism, and clinical treatments of epistaxis after NPC radiotherapy.Results: For treating NPC, radiation therapy is the primary therapeutic modality. However, radiotherapy can lead to varied degrees of harm to the neighboring tissues and is correlated with numerous complications. Among these complications, epistaxis is a common occurrence after NPC radiotherapy, owing to damage to the surrounding tissues caused by radiotherapy. Unfortunately, epistaxis, particularly carotid blowout, can have a dangerous course and a high mortality rate. Accurate understanding of epistaxis following radiotherapy, prompt bleeding cessation, and reduction of bleeding volume are key considerations. Nasal tamponade is a crucial rescue treatment, while tracheotomy is an active and effective method. Intravascular balloon embolization is a reliable and effective treatment method for ICA hemorrhage, and vascular embolization is the primary approach for treating external carotid artery maxillary bleeding. Implantation of a covered stent can achieve hemostasis without altering hemodynamics.Conclusion: A comprehensive approach utilizing these methods can improve the success rate of treating nosebleeds following NPC radiotherapy.HighlightsThe mortality rate for carotid blowout following radiotherapy for NPC is high.Radiation therapy and tumor condition are correlated with epistaxis in NPC.Treatment methods for NPC-related epistaxis include posterior nostril tamponade, endoscopic hemostasis, DSA, selective vascular embolization, and stent implantation.The use of a covered stent for NPC-related carotid blowout achieves hemostasis without altering blood perfusion.Effective and timely application of various hemostasis methods is key to improving the success rate of rescue, considering the characteristics of NPC-related epistaxis.


Assuntos
Embolização Terapêutica , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/complicações , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/complicações , Neoplasias Nasofaríngeas/radioterapia , Epistaxe/terapia , Epistaxe/complicações , Artérias Carótidas , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos
6.
J Neurointerv Surg ; 16(1): 31-37, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36898828

RESUMO

BACKGROUND: We hypothesized that left ventricular systolic dysfunction (LVSD) would lead to an ischemic core overestimation in patients with acute ischemic stroke (AIS), and impaired collateral status might partly mediate this effect. OBJECTIVE: A pixel-based analysis of CT perfusion (CTP) and follow-up CT was undertaken to investigate the optimum CTP thresholds for the ischemic core if overestimation was found. METHODS: A total of 208 consecutive patients with AIS with large vessel occlusion in the anterior circulation, who received initial CTP evaluation and successful reperfusion, were retrospectively analyzed and divided into an LVSD (left ventricular ejection fraction (LVEF) ratio <50%; n=40) and a normal cardiac function (LVEF≥50%; n=168) group. Ischemic core overestimation was considered when the CTP-derived core was larger than the final infarct volume. We investigated the relationship between cardiac function, probability for core overestimation, and collateral scores using mediation analysis. A pixel-based analysis was undertaken to define the optimum CTP thresholds for ischemic core. RESULTS: LVSD was independently associated with impaired collaterals (aOR=4.28, 95% CI 2.01 to 9.80, P<0.001) and core overestimation (aOR=2.52, 95% CI 1.07 to 5.72, P=0.030). In mediation analysis, the total effect on core overestimation is composed of the direct effect of LVSD (+17%, P=0.034) and the mediated indirect effect of collateral status (+6%, P=0.020). Collaterals explained 26% of the effect of LVSD on core overestimation. Compared with relative cerebral blood flow (rCBF) thresholds of <35%, <30%, and <20%, a rCBF <25% cut-off point had the highest correlation (r=0.91) and best agreement (mean difference 3.2±7.3 mL) with the final infarct volume to determine the CTP-derived ischemic core in patients with LVSD. CONCLUSIONS: LVSD increased the possibility of ischemic core overestimation on baseline CTP, partly due to impaired collateral status, and a stricter rCBF threshold should be considered.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico por imagem , Estudos Retrospectivos , Volume Sistólico , Tomografia Computadorizada por Raios X , Imagem de Perfusão , Função Ventricular Esquerda , Acidente Vascular Cerebral/diagnóstico por imagem , Reperfusão , Infarto
7.
J Neurointerv Surg ; 15(4): 380-386, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35396332

RESUMO

OBJECTIVE: Accurate prediction of cerebral aneurysm (CA) rupture is of great significance. We intended to evaluate the accuracy of the point cloud neural network (PC-NN) in predicting CA rupture using MR angiography (MRA) and CT angiography (CTA) data. METHODS: 418 CAs in 411 consecutive patients confirmed by CTA (n=180) or MRA (n=238) in a single hospital were retrospectively analyzed. A PC-NN aneurysm model with/without parent artery involvement was used for CA rupture prediction and compared with ridge regression, support vector machine (SVM) and neural network (NN) models based on radiomics features. Furthermore, the performance of the trained PC-NN and radiomics-based models was prospectively evaluated in 258 CAs of 254 patients from five external centers. RESULTS: In the internal test data, the area under the curve (AUC) of the PC-NN model trained with parent artery (AUC=0.913) was significantly higher than that of the PC-NN model trained without parent artery (AUC=0.851; p=0.041) and of the ridge regression (AUC=0.803; p=0.019), SVM (AUC=0.788; p=0.013) and NN (AUC=0.805; p=0.023) radiomics-based models. Additionally, the PC-NN model trained with MRA source data achieved a higher prediction accuracy (AUC=0.936) than that trained with CTA source data (AUC=0.824; p=0.043). In external data of prospective cohort patients, the AUC of PC-NN was 0.835, significantly higher than ridge regression (0.692; p<0.001), SVM (0.701; p<0.001) and NN (0.681; p<0.001) models. CONCLUSION: PC-NNs can achieve more accurate CA rupture prediction than traditional radiomics-based models. Furthermore, the performance of the PC-NN model trained with MRA data was superior to that trained with CTA data.


Assuntos
Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Estudos Retrospectivos , Estudos Prospectivos , Angiografia , Redes Neurais de Computação
8.
J Neurointerv Surg ; 15(2): 146-152, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35110399

RESUMO

BACKGROUND: The thrombus enhancement sign (TES) is thought to be associated with the source of the stroke and thrombus composition. We investigated whether this imaging sign along with other thrombus characteristics could be used to predict the successful first pass effect (FPE) of mechanical thrombectomy. METHODS: 246 consecutive patients with acute ischemic stroke in the anterior circulation with large vessel occlusion who underwent thrombectomy with a stent retriever and clot collection were included. Patients were divided into FPE (modified Thrombolysis in Cerebral Infarction (mTICI) grade 2c or 3)/non-FPE (mTICI 0-2b) and modified FPE (mFPE) (mTICI 2b-3)/non-mFPE (mTICI 0-2a) groups based on flow restoration after the first pass. TES presence, thrombus density, thrombus length, clot burden score, and thrombus composition were compared. The association between FPE and imaging biomarkers, along with clinical and interventional parameters, was investigated by univariate and multivariate analysis. RESULTS: FPE was achieved in 85 (34.6%) patients. TES presence was significantly lower in the FPE group (64.7% vs 80.7% in the non-FPE group, p=0.008) and mFPE group (69.1% vs 81.0% in the non-mFPE group, p=0.039). Histopathological examination revealed that TES (+) thrombi contained a higher fibrin/platelet proportion (50.9% vs 46.9% in TES (-) thrombi, p=0.029) and fewer erythrocytes (43.3% vs 47.3% in TES (-) thrombi, p=0.030). Thrombus characteristics, namely shorter thrombus length (p=0.032), higher erythrocyte proportions (p=0.026), and less fibrin/platelets (p=0.014), were confirmed in patients with FPE. In multivariable analysis, TES was the only independent predictor of FPE failure (OR 0.51, 95% CI 0.28 to 0.94; p=0.031). CONCLUSIONS: TES was independently associated with first pass angiographic failure in patients treated with a stent retriever.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , Isquemia Encefálica/terapia , Angiografia por Tomografia Computadorizada , Resultado do Tratamento , Trombose/diagnóstico por imagem , Trombose/cirurgia , Infarto Cerebral , Trombectomia/métodos , Stents , Angiografia Cerebral , Fibrina , Estudos Retrospectivos
9.
Adv Mater ; 34(42): e2200464, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36047924

RESUMO

Endothelialization of vascular implants plays a vital role in maintaining the long-term vascular patency. In situ endothelialization and re-endothelialization is generally achieved by selectively promoting endothelial cell (EC) adhesion and, meanwhile, suppressing smooth muscle cell (SMC) adhesion. Currently, such EC versus SMC selectivity is achieved and extensively used in vascular-related biomaterials utilizing extracellular-matrix-derived EC-selective peptides, dominantly REDV and YIGSR. Nevertheless, the application of EC-selective peptides is limited due to their easy proteolysis, time-consuming synthesis, and expensiveness. To address these limitations, a polymeric strategy in designing and finding EC-selective biomaterials using amphiphilic ß-peptide polymers by tuning serum protein adsorption is reported. The optimal ß-peptide polymer displays EC versus SMC selectivity even superior to EC-selective REDV peptide regarding cell adhesion, proliferation, and migration of ECs versus SMCs. Study of the mechanism indicates that surface adsorption of bovine serum albumin, an abundant and anti-adhesive serum protein, plays a critical role in the ECs versus SMCs selectivity of ß-peptide polymer. In addition, surface modification of the optimal ß-peptide polymer effectively promotes the endothelialization of vascular implants and inhibits intimal hyperplasia. This study provides an alternative strategy in designing and finding EC-selective biomaterials, implying great potential in the vascular-related biomaterial study and application.


Assuntos
Peptídeos , Soroalbumina Bovina , Polímeros , Adesão Celular , Materiais Biocompatíveis/farmacologia , Matriz Extracelular , Poder Psicológico
10.
Quant Imaging Med Surg ; 12(2): 1163-1171, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35111613

RESUMO

BACKGROUND: This study aimed to exam the effects of thin-slab maximum intensity projection (TS-MIP) of computed tomography angiography (CTA) for collateral score (CS) and clot burden score (CBS) evaluation in patients with large-vessel-occlusion (LVO) stroke in the anterior circulation. METHODS: Of 241 consecutive patients with LVO stroke admitted to our center between August 2015 and June 2020, 187 patients were enrolled. CS and CBS were evaluated on conventional CTA and TS-MIP separately. Outcome at 90 days was classified as good if modified Rankin scale (mRS) was ≤2 and as poor if mRS was >2. The correlations between CS and CBS and clinical outcomes were assessed. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic values of CS and CBS. Multivariate logistic regression analysis was performed to identify the independent predictors of 90-day good clinical outcomes. RESULTS: The correlation coefficient for clinical outcomes was significantly better for CS based on TS-MIP than that based on conventional CTA (-0.444 vs. -0.285, P=0.039); no significant difference was found in the CBS evaluation (TS-MIP: -0.356 vs. conventional CTA: -0.320, P=0.348). For predicting good clinical outcomes, TS-MIP-based CS was associated with larger area under the curve (AUC) (0.709 vs. 0.609, P=0.004) and higher sensitivity (69.1% vs. 42.0%, P=0.001) than CS based on CTA. In multivariable logistic regression analysis, the factors independently associated with good outcomes were National Institutes of Health Stroke Scale (NIHSS) score at admission (OR =1.147; P<0.001), TS-MIP-based CS (OR =0.326; P<0.001), final modified treatment in cerebral infarction (mTICI) score of 2b/3 (OR =0.098; P<0.001), and hemorrhagic transformation (OR =3.662; P<0.001). CONCLUSIONS: TS-MIP-CTA is superior to conventional CTA for evaluation CS and CBS, and TS-MIP-based CS may be a useful predictor of clinical outcome.

11.
Quant Imaging Med Surg ; 11(6): 2837-2860, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34079746

RESUMO

Recent progress in immunotherapy provides hope of a complete cure to cancer patients. However, recent studies have reported that only a limited number of cancer patients with a specific immune status, known as "cold tumor", can benefit from a single immune agent. Although the combination of immune agents with different mechanisms can partially increase the low response rate and improve efficacy, it can also result in more side effects. Therefore, discovering therapies that can improve tumors' response rate to immunotherapy without increasing toxicity for patients is urgently needed. Tumor interventional therapy is promising. It mainly includes transcatheter arterial chemoembolization, ablation, radioactive particle internal irradiation, and photodynamic interventional therapy based on a luminal stent. Interventional therapy can directly kill tumor cells by targeted drug delivery in situ, thus reducing drug dosage and systemic toxicity like cytokine release syndrome. More importantly, interventional therapy can regulate the immune system through numerous mechanisms, making it a suitable choice for immunotherapy to combine with. In this review, we provide a brief description of immunotherapies (and their side effects) on tumors of different immune types and preliminarily elaborate on interventional therapy mechanisms to improve immune efficacy. We also discuss the progress and challenges of the combination of interventional therapy and immunotherapy.

12.
Cell Rep ; 35(8): 109131, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34038723

RESUMO

Communication between biological components is critical for homeostasis maintenance among the convergence of complicated bio-signals. For therapeutic nanoparticles (NPs), the general lack of effective communication mechanisms with the external cellular environment causes loss of homeostasis, resulting in deprived autonomy, severe macrophage-mediated clearance, and limited tumor accumulation. Here, we develop a multistage signal-interactive system on porous silicon particles through integrating the Self-peptide and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide into a hierarchical chimeric signaling interface with "don't eat me" and "eat me" signals. This biochemical transceiver can act as both the signal receiver for amantadine to achieve NP transformation and signal conversion as well as the signal source to present different signals sequentially by reversible self-mimicking. Compared with the non-interactive controls, these signal-interactive NPs loaded with AS1411 and tanespimycin (17-AAG) as anticancer drugs improve tumor targeting 2.8-fold and tumor suppression 6.5-fold and showed only 51% accumulation in the liver with restricted hepatic injury.


Assuntos
Comunicação Celular/imunologia , Nanopartículas/metabolismo , Neoplasias/imunologia , Humanos , Modelos Moleculares , Estadiamento de Neoplasias , Transdução de Sinais
13.
J Neurol Sci ; 424: 117294, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33799211

RESUMO

Aneurysmal subarachnoid hemorrhage is caused by intracranial aneurysm (IA) rupture and results in high rates of mortality and morbidity. Factors contributing to IA generation, growth and rupture can involve genetics, injury, hemodynamics, environmental factors, and inflammation, in which inflammatory factors are believed to play central roles in the whole natural history. Inflammatory reactions that contribute to IA development may involve synthesis of many functional proteins and expression of genes induced by changes of blood flow, external stimuli such as smoking, internal balance such as hormonal status changes, and blood pressure. Meanwhile, inflammatory reactions itself can evoke inflammatory cytokines release and aggregation such as MMPs, MCP-1, TNF-α and ZO-1, directly or indirectly promoting aneurysm growth and rupture. However, the details of these inflammatory reactions and their action on inflammatory chemokines are still unknown. Moreover, some agents with the function of anti-inflammation, lipid-lowering, antihypertension or inflammatory factor inhibition may have the potential benefit to reduce the risk of aneurysm development or rupture in a group of population despite the underlying mechanism remains unclear. Consequently, we reviewed the potential inflammatory responses and their mechanisms contributing to aneurysm development and rupture and sought intervention targets that may prevent IA rupture or generation.


Assuntos
Aneurisma Roto , Aneurisma Intracraniano , Hemorragia Subaracnóidea , Aneurisma Roto/complicações , Humanos , Inflamação , Aneurisma Intracraniano/complicações , Fatores de Risco , Fator de Necrose Tumoral alfa
14.
J Nanobiotechnology ; 19(1): 17, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422073

RESUMO

BACKGROUND: Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. RESULTS: The particle size of the micelles was 42 nm, the zeta potential increased from - 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. CONCLUSIONS: This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Terapia Genética/métodos , Micelas , Neoplasias da Próstata/tratamento farmacológico , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular , Docetaxel/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Poliésteres , Neoplasias da Próstata/patologia , RNA Interferente Pequeno/farmacologia
15.
J Neurointerv Surg ; 13(6): 563-567, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32859747

RESUMO

BACKGROUND: Acute ischemic stroke can be caused by in situ stenotic vessel occlusion. In the present study, we compared the extent of arterial wall damage and miRNA expression following stent retriever use under normal and stenotic conditions. METHODS: The stent retriever procedure was simulated in three dogs by the creation of four stenoses on each side of the common carotid artery (CCA) to allow five stent passages. Device safety was also assessed in normal control models by five passages through both CCAs. Device manipulation-related damage to the arterial walls was evaluated and compared between groups by angiography and pathological analysis. Real-time PCR was used to evaluate the differences in the expression of miRNAs between the two groups. RESULTS: Twenty-four stenoses were created in three model dogs, and the mean stenosis rate was 65.58%±18.95%. Angiography revealed greater vasospasm in the stenotic group than in the non-stenotic group (1.17±0.17 vs 0.5±0.23; P=0.04). Pathological examination revealed that SR passage through the stenotic lumen caused higher injury scores (1.63±0.19 vs 0.25±0.09 for the non-stenotic lumen; P<0.001), more endothelial denudation (1.79±0.13 vs 0.58±0.13 for the non-stenotic lumen; P<0.001), and increased thrombus deposition (0.71±0.14 vs 0±0 for the non-stenotic lumen; P<0.001). miR21-3p, miR29-3p, and miR26a were upregulated in stenotic vessels compared with non-stenotic vessels after SR thrombectomy (P<0.001). CONCLUSION: In our model dogs, SR thrombectomy resulted in more severe tissue damage to the arterial wall under stenotic conditions than under non-stenotic conditions. The damage may have resulted from upregulation of miR21-3p, miR29-3p, and miR26a expression.


Assuntos
Lesões das Artérias Carótidas/metabolismo , Estenose das Carótidas/metabolismo , Endotélio Vascular/lesões , Endotélio Vascular/metabolismo , MicroRNAs/biossíntese , Trombectomia/efeitos adversos , Angiografia/métodos , Animais , Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/genética , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/cirurgia , Estenose das Carótidas/genética , Estenose das Carótidas/cirurgia , Modelos Animais de Doenças , Cães , MicroRNAs/genética , Stents , Trombectomia/tendências , Resultado do Tratamento
16.
Br J Neurosurg ; : 1-5, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32988230

RESUMO

OBJECTIVE: The aim of this study was to identify independent anatomic, morphologic and hemodynamic features of the ACoA (anterior communicating artery) complex that serve as risk factors for the occurrence of ACoA aneurysms. METHODS: Fifteen consecutive patients with 15 ACoA aneurysms were included. Computational fluid dynamics (CFD) simulations based on patient-specific models were carried out using 3D time-of-flight magnetic resonance angiography (3D-TOF-MRA) images. A reverse reconstruction technique was used to generate a pre-aneurysm vessel anatomy. Geometric parameters and hemodynamic changes were compared and evaluated. RESULTS: The overall prevalence of symmetric, dysplastic, and absent A1 segments were 53.3%, 26.7%, and 20%. The mean wall shear stress (WSS) of the absent group (AG) was significantly higher than that of the symmetric group (SG) and dysplastic group (DG). The absolute mean A1 artery flow rate (410.2 ± 88 versus 439.4 ± 101 mL/min; p = .45) of the aneurysm side was similar between the SG and DG but significantly higher in the AG (528.1 ± 77 mL/min; p < .05). The A1-A2 angles of the aneurysm side showed no significant differences among the 3 groups (p = .32). However, the mean A1-A2 angle on the aneurysm side was smaller than the contralateral A1-A2 angle (101.9 ± 9.1˚ versus 120.3 ± 7.7˚; p <.05). A regression analysis demonstrated that high WSS was significantly associated with a large A1-A2 ratio (R2=0.52; p <.05). CONCLUSIONS: ACoA aneurysms are a high-WSS pathology. Severe flow impingement and the anatomic vasculature structures play a role in triggering the occurrence of ACoA aneurysms.

17.
Quant Imaging Med Surg ; 10(5): 1045-1057, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32489928

RESUMO

The COVID-19 pandemic seriously threatens the lives of the general public and poses momentous challenges to all medical workers, including those engaged in interventional radiology, who play an important role in the diagnosis and treatment of various diseases. To further standardize the prevention and control of nosocomial infections and ensure the safety of doctors and patients, the Chinese Society of Interventional Radiology (CSIR) organized multidisciplinary experts in the field of interventional radiology in China to prepare an "Expert Consensus" elaborating and summarizing the protective strategies and suggestions for medical workers in the field of interventional radiology when they engage in interventional diagnosis and treatment activities against the background of novel coronavirus infection control. The aim is to provide a reference for interventional procedures in hospitals and other medical institutions at all levels in China and worldwide. The key points include the following: (I) non-emergency interventional diagnosis and treatment should be suspended while work is ongoing to prevent and control the spread of COVID-19; (II) protective measures should be taken according to the appropriate level designated for COVID-19 infection prevention and control; (III) patients should take measures to protect themselves when they want to see a doctor, including accessing outpatient services online and other relevant channels of consultation.

18.
Small ; 15(49): e1904979, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31659867

RESUMO

Drug-eluting stents (DESs) are promising candidates for treating human oesophageal cancer. However, the use of DESs to assist photodynamic therapy (PDT) of orthotopic oesophageal tumors is not yet demonstrated to the best of current knowledge. Herein, through an electrospinning technology it is shown that oxygen-producing manganese dioxide nanoparticles are embedded into elelctrospun fibers, which are subsequently covered onto stents. Upon implantation, the nanoparticles are gradually released from the fibers and then diffuse into the nearby tumor tissue. Then, the hypoxic microenvironment can be effectively alleviated by reaction of MnO2 with the endogenous H2 O2 within the tumor. After demonstrating the excellent PDT efficacy of the stents in a conventional subcutaneous mouse tumor model, such stents are further used for PDT treatment in a rabbit orthotopic oesophageal cancer model by inserting an optical fiber into the tumor site. Greatly prolonged survival of rabbits is observed after such intraluminal PDT treatment. Taken together, this work shows that the fiber-covered stent as a nanoparticle delivery platform can enable effective PDT as a noninvasive treatment method for patients with advanced-stage oesophageal cancer.


Assuntos
Neoplasias Esofágicas/terapia , Fotoquimioterapia/métodos , Animais , Stents Farmacológicos , Peróxido de Hidrogênio/química , Compostos de Manganês/química , Nanopartículas/química , Óxidos/química , Oxigênio/química , Coelhos
19.
Quant Imaging Med Surg ; 9(6): 960-967, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31367550

RESUMO

BACKGROUND: Diabetes mellitus (DM) is associated with increased prevalence and severity of atherosclerosis. This study aimed to assess the prevalence and location of atherosclerosis in intracranial and extracranial vessels in diabetic patients and to investigate their association with ischemic stroke subtype. METHODS: Diabetes patients (n=128) and nondiabetic patients (n=195) were enrolled. Brain MRI, MR angiography, and digital subtraction angiography (DSA) imaging findings in the two groups were retrospectively compared. The characteristics of atherosclerosis (prevalence, location, severity) and collateral flow in diabetic and nondiabetic patients and their association with stroke subtype were analyzed. RESULTS: Atherosclerosis in extracranial vessels was more common in diabetes patients than in nondiabetic patients (43.8% vs. 23.1%; P<0.001). Symptomatic stenoses were commonly in the proximal internal carotid artery (ICA) and proximal vertebral artery (pVA). Diabetes patients were more likely to have lacunar infarction (49.2% vs. 32.3%; P=0.002) and less likely to have large artery infarct (36.7% vs. 48.2%; P=0.042). DM (OR, 2.03; 95% CI, 1.96-4.30; P=0.006) and age >65 years (OR, 2.55; 95% CI, 1.24-5.22; P=0.011) were independent risk factors for lacunar infarct. Diabetes patients with symptomatic extracranial stenosis or occlusion, combined with good collateral circulation, had significantly higher risk of lacunar infarction than nondiabetic patients (47.8% vs. 30.5%; P=0.045). CONCLUSIONS: DM aggravates the severity of extracranial atherosclerosis. Lacunar stroke is relatively common in diabetic patients and could even be due to large artery disease (LAD).

20.
Acta Biomater ; 94: 295-305, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31195144

RESUMO

Aneurysmal subarachnoid hemorrhage (SAH) causes high rates of mortality and morbidity. A covered stent is an effective endovascular treatment for complicated aneurysms intractable to endovascular coiling and surgical clipping. However, in-stent restenosis and delayed endothelialization are the main challenges contributing to its safety. In this study, we designed a biofunctional stent covered with dual drug-loaded electrospun fibers to achieve programmed vascular endothelial growth factor (VEGF) and paclitaxel (PTX) release for the early promotion of stent endothelialization and long-term inhibition of stenosis caused by smooth muscle hyperplasia. By encapsulating PTX-loaded mesoporous silica nanoparticles (MSNs) within electrospun polylactic acid (PLA) fibers, the release period of PTX was effectively extended. Furthermore, VEGF was conjugated onto the surface of the membrane by reacting with polydopamine (PDA) for quick release. The in vitro drug release profile revealed the sustained release of PTX, which persisted for 63 days without early burst release, while up to 87.05% of VEGF was rapidly released within 3 days. After 6 days of incubation, cell experiments demonstrated that the dual drug-loaded scaffold effectively prompted endothelial cell proliferation (488% vs. 386% in the control group, P = 0.001) and inhibited the proliferation of smooth muscle cells (SMCs) using the 21-day extracts (155% vs. 303% in the control group, P = 0.039). Animal studies showed that compared to bare stents, the drug-loaded covered stents improved the immediate- and mid-term complete aneurysm occlusion rates (P < 0.05). The drug-loaded covered stents also showed earlier endothelialization promotion and better lumen restenosis than normal covered stents (0% vs. 25%, P = 0.29) for 12 weeks. Overall, a programmed dual drug-loaded scaffold that effectively occluded the aneurysm sac was developed in this study, and the discrete release of VEGF and PTX promoted endothelialization and prevented in-stent stenosis. This study provided a new method to improve the biosafety of implanted covered stents for the treatment of intracranial aneurysms. STATEMENT OF SIGNIFICANCE: Aneurysmal subarachnoid hemorrhage (SAH) is one of the most common hemorrhage stroke resulted in a nearly 40% mortality and 33% morbidity due to sudden rupture of an intracranial aneurysm. Endovascular coil embolism is a popular treatment for aneurysm but this technique run high risk of bleeding, mass effect, low complete occlusion rate and higher recanalization rate due to its operation conducted within aneurysm sac. A bio-functional membrane knitted by dual-drug loaded electrospun fibers covered on a stent was designed to realize programed vascular endothelial growth factor and paclitaxel release for the early promotion of vascular endothelium and long-term inhibition of stenosis caused by smooth muscle hyperplasia. This study provides new method to improve the biosafety of covered stent insertion for the treatment of intracranial aneurysms.


Assuntos
Materiais Revestidos Biocompatíveis/química , Constrição Patológica/prevenção & controle , Stents Farmacológicos , Nanofibras/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Prótese Vascular , Sobrevivência Celular , Materiais Revestidos Biocompatíveis/metabolismo , Cães , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Indóis/química , Aneurisma Intracraniano/tratamento farmacológico , Masculino , Nanopartículas/química , Paclitaxel/química , Paclitaxel/farmacologia , Poliésteres/química , Polímeros/química , Porosidade , Próteses e Implantes , Dióxido de Silício/química , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/química , Fator A de Crescimento do Endotélio Vascular/farmacologia
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