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Objective:To prepare a phase-change lipid nanoparticle modified by tumor homing membrane-penetrating peptide (tLyP-1) and carrying paclitaxel (PTX) engineered by metal polyphenol network (TA-Fe 3+ ), and evaluate the therapeutic effects of tumor targeting, ultrasound/photoacoustic imaging and photothermal combined chemotherapy in vitro. Methods:Phase-change lipid nanoparticles (t-P@TFP) with TA-Fe 3+ engineered PTX mediated by tLyP-1 were prepared by solvent replacement method, thin film hydration method and double emulsification method. Its detection and characterization, in vitro targeting ability, photothermal conversion ability, in vitro photoacoustic and ultrasonic imaging ability, CCK-8 method, cell live and death double staining method and flow cytometry method were used to detect the safety of nanoparticles and the killing effects of different nanoparticles on 4T1 cells. Results:t-P@TFP nanoparticles were successfully prepared. Transmission electron microscopy showed that the nanoparticles were spherical with uniform shape and size, with a particle size of (209.8±1.56)nm and a potential of (-25.9±1.36)mV. Laser confocal scanning microscopy showed that t-P@TFP nanoparticles could gather around 4T1 cells in a targeted manner. It had an efficient photothermal conversion effect, and nanoparticles could quickly become microbubbles after being irradiated by near-infrared laser, which enhanced the in vitro ultrasonic imaging effect; The photoacoustic signal of nanoparticles increased with the increase of concentration. CCK-8 method, double staining of living and dead cells and flow cytometry showed that t-P@TFP combined photothermal chemotherapy had the best anti-tumor effect. Conclusions:t-P@TFP nanoparticles are successfully prepared. The nanoparticles have good targeting ability for photoacoustic and ultrasonic imaging and have good photothermal effect, killing breast cancer cells, which is expected to realize the integration of diagnosis and treatment.
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The traditional classification, diagnosis, and treatment of intracranial aneurysms are based on the characteristics of their vascular lumen. However, in the past few years, some advances in MRI technology with high-resolution imaging can assess the pathology of intracranial vascular walls. Compared with traditional methods of computed tomography angiography, magnetic resonance angiograhpy, and digital subtraction angiography, high resolution magnetic resonance imaging technology can help us to newly understand the disease by directly evaluating the characteristics of vascular wall, such as aneurysm wall thickness, inflammation, enhancement, permeability and hemodynamics. At present, high-resolution magnetic resonance imaging is increasingly used in clinic to assess the rupture risk of intracranial aneurysms, which is of great significance for guiding the diagnosis and treatment of intracranial aneurysms.
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Humanos , Aneurisma Roto/diagnóstico por imagen , Angiografía Cerebral , Aneurisma Intracraneal/diagnóstico por imagen , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Medición de Riesgo , TecnologíaRESUMEN
The subarachnoid hemorrhage (SAH) caused by ruptured intracranial aneurysms (IAs) is always a lethality. Increasing evidence suggests a familiar aggregation of IA occurrence, which may relate to genetics and there might be an increasing number of IAs in IA families when mutation of disease genes is aggregating. With the progress in the study of familiar intracranial aneurysms (FIAs), a large number of chromosome fragments are found to be related with IAs, such as 1p36, 5q31, 7q11, 14q22, 17cen, 19q13, Xp22. Further studies indicated that mutation of several genes could be the cause of FIAs, including TNFRSF13B, ANRIL, SOX17, ADAMTS15, RNF213 and LOXL2. The independent genetic epidemiologic study on aneurysm families can be used to discover the related genes more effectively, and to explore the mechanism of occurrence of IAs. It's also the precondition for the prevention of disease.
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Humanos , Adenosina Trifosfatasas , Aminoácido Oxidorreductasas , Investigación Genética , Aneurisma Intracraneal , Genética , Factores de Riesgo , Ubiquitina-Proteína LigasasRESUMEN
<p><b>OBJECTIVE</b>To identify factors that predictive of quality of life after microsurgical removal of petroclival meningiomas.</p><p><b>METHODS</b>A consecutive series of 71 cases of petroclival meningiomas received microsurgical removal between July 1991 and April 2010 were analyzed retrospectively. Quality of life was measured using Karnofsky performance scale (KPS). Complete pre-operative, post-operative and follow-up data were obtained from all 71 patients including 18 male and 53 female patients with the mean age of (47 ± 11) years (aging from 15 to 68 years). The duration between onset of symptoms and diagnosis ranged from 1 week to 180 months with the mean duration of (32 ± 30) months. And the tumor size was 15-72 mm with the average of (44 ± 11) mm. Main presentations included headache, unsteady gait, hemiparesis, dysphagia, hoarseness, facial numbness or pain, Bell's palsy, hearing impairment etc. The preoperative KPS was 40-100 with the average of 69 ± 11. The retrosigmoid (-transtentorial) approach was performed in most cases (91.5%). Intergroup χ² test and logistic regression analysis were conducted for prognostic factor characterization.</p><p><b>RESULTS</b>The gross total resection (all were Simpson gradeII) reached in 48 cases (67.6%) and 1 case died postoperatively. The main new neurological dysfunctions were cranial nerve paralysis and hemiplegia with the postoperative KPS of 20-100 with the average of 73 ± 16.Sixty-four cases were followed for 4-132 months with the average of (61 ± 48) months. Seven patients died during follow-up, tumor recurrence and progression were identified in 6 and 8 cases, respectively. The KPS at the last visit ranged from 50 to 100 with the average of 83 ± 13. The extent of tumor resection (OR = 0.280, 95% CI: 0.081-0.967, P = 0.044), preoperative brainstem edema (OR = 0.100, 95% CI: 0.027-0.372, P = 0.001), relationships between tumor and neurovascular structures (OR = 0.288, 95% CI: 0.084-0.985, P = 0.047) and depth of invasion into cavernous sinus (OR = 0.254, 95% CI: 0.061-1.057, P = 0.048) had significant correlations with the prognostic quality of life.</p><p><b>CONCLUSIONS</b>With regard of the choice of surgical approaches, the extent of tumor resection, the protection of neurovascular structures surrounding the tumor and the management of perioperative period, the therapeutic strategies for each patient should be customized to achieve better prognosis.</p>
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Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Estudios de Seguimiento , Neoplasias Meníngeas , Diagnóstico , Cirugía General , Microcirugia , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE@#To investigate the protective effect of combined ischemic preconditioning and postconditioning against cerebral ischemia/reperfusion (I/R) injury and the potential mechanism.@*METHODS@#Sixty SD rats were randomized into a sham operation group, a brain I/R group (model group), a brain I/R plus preconditioning group (preconditioning group), a brain I/R plus postconditioning group (postconditioning group), and a brain I/R plus preconditioning and postconditioning group (combined intervention group). The rat brain I/R injury model was created by suture emboli method. Preconditioning was induced by 3 cycles of 15 s occlusion followed by 30 s recanalization of the middle cerebral artery twice respectively at 24 h and 1 h before model creation, and postconditioning was elicited by 3 cycles of 30 s reperfusion followed by 15 s ischemia before long time reperfusion. The rats were sacrificed at 48 h after the reperfusion. The cerebral infarct volume and oxidative stress parameters as well as p-Akt and p-ERK1/2 protein expressions in the brain tissues were determined.@*RESULTS@#The cerebral infarct volumes showed no significant difference between the preconditioning group and the postconditioning group (P>0.05), but both were smaller than that in the model group and larger than that in the combined intervention group (all P values0.05), but p-Akt expression was slightly upregulated and p-ERK1/2 was remarkably down-regulated (P<0.05 and P<0.01) In the postconditioning group, the level of oxidative stress was significantly decreased, and p-Akt expression was dramatically increased with a mild down-regulation of p-ERK1/2 expression (P<0.01 and P<0.05). In the combined intervention group, the oxidative stress decrease the p-Akt expression rise and p-ERK1/2 expression inhibition were significantly greater than those in either the preconditioning group or the postconditioning group (all P values<0.01).@*CONCLUSION@#Combined treatment of preconditioning and postconditioning exerts stronger protective effect against cerebral I/R injury than either preconditioning or postconditioning alone. The mechanism is possibly due to the different but complementary protection of preconditioning and postconditioning against I/R injury.
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Animales , Ratas , Isquemia Encefálica , Patología , Cerebro , Patología , Regulación hacia Abajo , Poscondicionamiento Isquémico , Precondicionamiento Isquémico , Estrés Oxidativo , Ratas Sprague-Dawley , Daño por Reperfusión , Terapéutica , Regulación hacia ArribaRESUMEN
Objective:To study the effect of microsurgery for parasellar menningiomas and to analyze the impact factors of recurrence. Methods:Clinical and follow-up data in a consecutive series of 134 patients with parasellar meningiomas were retrospectively analyzed. Results:A total of 109 patients (81.3%) had radical removal (Simpson grade I and II), and 116 patients were followed up for an average period of 81.6 months. The mean quality of life score (KPS) was 91.9, 90 patients regained full daily activity and 16 patients were able to take care of themselves. Oculomotor paralysis occurred in 7 patients, epilepsy in 8, and another 9 patients suffered hemispheral paralysis. Tumor recurred atfer the radical removal in 12 out of the 96 follow-up patients (12.5%). Tumor progressed atfer subtotal removal in 12 out of the 20 follow-up patients (60%). Tumor with cavernous sinus (CS) invasion had significantly higher risk of recurrence campared with non-CS invasion (P=0.043). The recurrence rate increased with the pathological grade (P<0.01). Conclusion:Patients with parasellar meningiomas undergoing microsurgical resection may have a good long-term function outcome. For most patients, total removal by microsurgery is the ifrst choice. Careful follow-up is needed if tumor invaded the CS and radiosurgery is proposed for WHO grade 1 and 2.