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To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db-/- mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db-/- mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db-/- mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db-/- group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db-/- mice (P < 0.05). NF-κB levels were obviously higher in the db/db-/- group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db-/- mice (P < 0.05). There was a trend of increased autophagosomes in db/db-/- mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db-/- mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db-/- mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.
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Envejecimiento/metabolismo , Beclina-1/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , FN-kappa B/metabolismo , Extractos Vegetales/uso terapéutico , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Animales , Beclina-1/agonistas , Disfunción Cognitiva/genética , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Relación Dosis-Respuesta a Droga , Ginkgo biloba , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/antagonistas & inhibidores , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
AIMS: To discuss the clinical characteristics and prognosis of chordoid meningioma (CM). METHODS AND RESULTS: Tumour samples of CM from 30 patients were re-examined. The postoperative outcomes were analyzed on the basis of clinical observations. The survival probabilities were calculated using the Kaplan-Meier method. Thirty-two operations were performed in 30 cases, including 27 operations for total removal and five operations for subtotal removal. The median follow-up period was 34.0 months. Tumour recurred in five patients, with a median recurrence time of 32.0 months. No systemic manifestations of Castleman's syndrome were found. The majority (80%) of tumours were found in the supratentorial compartments. The MIB-1 labelling index (MIB-1 LI) varied from 1% to 10%. In univariate analyses, the presence of aggressive factors (P = 0.001) and the extent of resection (P = 0.037) were related to progression-free survival (PFS). The MIB-1 LI (P = 0.50) and postoperative radiotherapy (P = 0.62) were not related to PFS. CONCLUSIONS: Chordoid meningioma is a rare subtype of meningioma, and is often found supratentorially. There is an absence of association with Castleman's syndrome. Aggressive factors and the extent of resection are helpful in predicting recurrence. It might be more pertinent to downgrade CM to grade I, unless it shows aggressive factors.
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Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Notocorda/patología , Neoplasias Supratentoriales/diagnóstico , Adolescente , Adulto , Anciano , Encéfalo/patología , China/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/cirugía , Meningioma/mortalidad , Meningioma/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Supratentoriales/mortalidad , Neoplasias Supratentoriales/cirugía , Tasa de Supervivencia , Adulto JovenRESUMEN
AIM: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6). METHODS: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected. RESULTS: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA1C, and TG of MIS group were all significantly elevated (all P<0.05), and HDL-C levels were considerably reduced (P<0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P<0.05). CONCLUSION: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS.
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OBJECTIVE: To describe the personal experiences of treating cavernous sinus hemangiomas (CSH) with gamma knife or cyberknife and evaluate the medium and long-term outcomes. METHODS: From June 1999 to December 2008, 20 CSH patients were treated by radiosurgery (gamma knife or cyberknife). Among them, 11 had residual tumor after surgery and 9 were diagnosed by neuroradiology. All cases on magnetic resonance imaging (MRI) showed well-defined and homogeneous hyperintensity on T2-weighted images. The mean maximum diameter of tumors was 38.7 ± 9.3 mm (range: 23.0 - 60.6). The volume of tumors ranged between 4.1 - 52.6 cm(3) with a mean of (18.7 ± 12.5) cm(3). The tumor margin dose irradiated by gamma knife ranged from 9 to 16 Gy (mean 12.3 ± 2.3 Gy). The tumor margin dose irradiated by cyberknife was 20 - 21 Gy in 3 fractions. The mean follow-up period was (60 ± 32) months (range: 12 - 120). RESULTS: Follow-up imaging showed tumor volume decreased over 90% (n = 5), tumor regressed over 50% in volume (n = 9) and no change in tumor volume (n = 1). One patient with large tumor (irradiated 10 Gy) was operated by open surgery at 5 months after gamma knife. Four giant tumors decreased over 50% in volume after cyberknife. Neurologically, none of these patients showed any deterioration. And 16 patients demonstrated an obvious improvement after radiosurgery. At the last follow-up, there were no complications related to radiosurgery. CONCLUSION: Radiosurgery (Gamma knife or cyberknife) is a safe and effective modality for small- and medium-sized CSH. Fractionated Cyberknife proves to be an effective treatment for large or giant CSH. Thus radiosurgery will be an alternative option to surgery.
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Hemangioma Cavernoso del Sistema Nervioso Central/cirugía , Radiocirugia , Adulto , Anciano , Seno Cavernoso/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine differential gene expression of hippocampus in rats following complete cerebral ischemia with treatment of profound hypothermia compared to normothermia. METHODS: Six rats got 5 minutes of complete cerebral ischemia with circulatory arrest and randomly divided into two groups: normothermia ischemia group (37 +/- 0.3 degrees C, n = 3) and profound hypothermia ischemia group (18 +/- 0.5 degrees C, n = 3). Affymetrix U34A rat arrays were applied to detect the difference of gene expression profile in hippocampus between the two groups. RESULTS: Expression profiles of a total of 75 transcripts in the profound hypothermia ischemia group were statistically different from those of the normothermia ischemia group, and 33 of them were significantly up-regulated and other 42 were significantly down-regulated (p < 0.07). CONCLUSIONS: Compared with normothermia, profound hypothermia had a significant effect on the gene expression profiles following complete cerebral ischemia, which may be involved in the mechanisms of cerebral protection by profound hypothermia.
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Isquemia Encefálica/patología , Isquemia Encefálica/terapia , Regulación de la Expresión Génica/fisiología , Genómica/métodos , Hipocampo/metabolismo , Hipotermia Inducida/métodos , Animales , Bases de Datos Genéticas/estadística & datos numéricos , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Distribución Aleatoria , RatasRESUMEN
Aim. In this study we examined the influence of tetrandrine (Tet) on the neuroprotective effects of glutathione (GSH) in the 6-hydroxydopamine- (6-OHDA-) lesioned rat model of Parkinson's disease (PD). Methods. Levels in the redox system, dopamine (DA) metabolism, dopaminergic neuronal survival, and apoptosis of the substantia nigra (SN) and striatum, as well as the rotational behavior of animals were examined after a 50-day administration of GSH + Tet (or GSH) and/or L-3,4-dihydroxyphenylalanine (L-dopa) to PD rats. Ethics Committee of Huashan Hospital, Fudan University approved the protocol (number SYXK2009-0082). Results. Administration of GSH or Tet alone did not show any significant effects on the factors evaluated in the PD rats. However, in the GSH + Tet group, we observed markedly decreased oxidative damage, inhibition of DA metabolism and enhanced DA synthesis, increased tyrosine hydroxylase- (TH-) immunopositive neuronal survival, and delayed apoptosis of dopaminergic neurons in the SN. Animal rotational behavior was improved in the GSH + Tet group. Additionally, coadministration of GSH + Tet appeared to offset the possible oxidative neurotoxicity induced by L-dopa. Conclusion. In this study, we demonstrated that tetrandrine allowed occurrence of the neuroprotective effect of glutathione probably due to inhibition of P-glycoprotein on 6-hydroxydopamine-lesioned rat models of Parkinson's disease, including rats undergoing long-term L-dopa treatment.
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BACKGROUND: Papillary meningioma (PM) is an uncommon meningioma subtype, and the clinical characteristics remain unclear. OBJECTIVE: To determine the clinical characteristics and prognosis of PM. METHODS: The clinical data of 30 PM patients were collected, the samples were reexamined, and the patients' prognoses were based on clinical observations and calculated according to the Kaplan-Meier method. RESULTS: The 30 patients included 16 males and 14 females (median: 34.0 years upon initial diagnosis). Of the 48 intracranial operations in the 30 patients, total removal was attained in 34 surgeries, and subtotal removal in 14 surgeries. Radiotherapy was provided in 20 patients. In 40 specimens with follow-up, 29 attained the positive aggressive factors. Six tumors showed positive progestogen receptor (PR) combined with negative Bcl-2. The median follow-up period was 39.0 months. Tumor recurrence occurred in 18 patients (median: 17.0 months); the recurrence rates following total removal and subtotal removal were 57.1% and 100%, respectively. Fourteen patients died of the recurrence. In the univariate analyses, positive aggressive factors (P = .021), positive PR combined with negative Bcl-2 immunoreactivity (P = .011), the extent of resection (P = .001), and radiotherapy (P = .002) were significantly related to progression-free survival. The MIB-1 labeling index was not significantly related to progression-free survival (P = .88). CONCLUSION: PM is a rare subtype of meningioma with a tendency of recurrence. The extent of resection is an important prognosis factor. The presence of positive histopathological index increases the recurrence risk. Positive PR combined with negative Bcl-2 immunoreaction might predict a good prognosis. Postoperative radiotherapy may play a vital role in prolonging the time to tumor recurrence.