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Objective:To explore the effects of early-life maternal deprivation on depressive-like behavior and neurogenesis in the granular layer of hippocampus in adolescent rats (6-7 weeks old).Methods:Neonatal rats were randomly divided into maternal deprivation group and control group, with 3 litters in each group.Rats in the maternal deprivation group were given maternal deprivation from 1 to 14 days after birth and rats in the control group were caged with the mother rats and raised normally.The body weight of rats at 5-6 weeks old was recorded and the increased body weight was calculated.When the rats were 6 weeks old, the sucrose preference test was carried out.Then the rats were killed and immunofluorescence histochemistry was applied to compare the expression of Ki67 and Nestin positive cells in the dentate gyrus of hippocampus.SPSS 22.0 software was used for statistical analysis.The data of the two groups were tested to conform to the normal distribution, and then t-test was carried out. Results:There was significant difference in body weight growth between the two groups at the age of 5-6 weeks.Compared with the control group, rats in the maternal deprivation group had lower body weight growth ((20.57±2.19) g, (30.57±1.25) g, t=3.96, P<0.01)) and lower sucrose preference rate((58.38±53.14)%, (73.88±3.67)%, t=3.21, P<0.01). The results of immunofluorescence showed that the number of Ki67 positive cells in the granular layer of hippocampus in the maternal deprivation group was less than that in the control group ((5.13±0.31), (7.60±0.38), t=5.09, P<0.01), and the number of Nestin immunofluorescence positive cells was more than that in the control group ((16.65±0.79), (7.64±0.70), t=8.51, P<0.01). The Nestin immunofluorescence positive cells in the maternal deprivation group had more protrusions and branches, and the morphology was similar to astrocytes, while the immunofluorescence positive cells in the control group had fewer protrusions, and the cell body was oval. Conclusions:Early-life maternal deprivation leads to depressive-like behavior in adolescent rats, which may be associated with the decrease of neurogenesis and activation of astrocytes in the dentate gyrus of the hippocampus.
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Objective To conduct an in-depth analysis on the correlation of miRNA and Alzheimer disease (AD) pathogenesis and provide an experimental basis for AD potential biomarkers by analysis of serum miRNA expression profiles in AD patients. Methods The miRNA expression profiles were exmined in 7 severe AD patients and 5 normal controls using high-throughput sequencing and bioinformatic analysis. Results Compared with the normal controls, there were serum differential expression of 112 miRNAs (DEmiRNAs) including 57 being up-regulated and 55 being down-regulated in patients with severe AD (P<0.05). GO-term function enrichment analysis showed that DEmiRNAs participated in the protein binding, ion binding, transcription metal binding, and biological metabolism and regulation process of organelle and cell membrane, etc. KEGG pathway enrichment analysis found that PI3K-Akt signal pathway was an important pathway of target genes. Conclusion The differential expression of serum miRNAs may be potential biomarkers of AD and the target genes of DEmiRNAs are related to the pathological changes of AD.
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Objective In order to evaluate that whether Pluronic P85 coated poly(butylcyanoacrylate) nanoparti-cles was able to deliver antiepileptic drug phenytoin into the brain va bypassing mesial temporal lobe epilepsy (MTLE)-induced Pgp in a rat model of MTLE. Methods The rat model of MTLE, induced by li-pilocarpine, was divided in-to two groups (6 for nanoparticle drug group and 7 for PHT drug group). Immunohistochemistry assay was performed to detect Pgp expression at the hippocampus. Nanoparticles were prepared by interfacial polymerization method. Dialysate samples of brain were collected at 30, 60, 120, 180, 240 and 300 min after drug administration by microdialysis tech-nology. Samples were analyzed by high performance liquid chromatography (HPLC). Results The area under the curve (AUC) ratio of brain/plasma in Nanoparticle drug group was 0.370.10 which was significantly higher compared with 0.190.06 in conventional PHT drug group (P<0.05). The Pgp immunopositive area, as assessed by analysis of labeled surface area, was higher in the DG, CA3 and CA1 sector in the hippocampus of MTLE rats when compared to the normal rats. Conclusions Pluronic P85 coated PBCA nanoparticles can significantly deliver PHT into brain via bypassing MTLE-induced Pgp in a rat model of MTLE.
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ObjectiveTo investigate the efficacy of intensity-modulated radiotherapy (IMRT) in treating large primary hepatocellular carcinoma (LHCC) which is unsuitable for surgery or has poor response to radiofrequency ablation, interventional therapy, and other local treatments, and to identify the prognostic factors for survival. MethodsWe retrospectively analyzed the clinical data of 29 LHCC patients who received IMRT from April 2008 to August 2011. There were five fractions per week and the dose for each fraction was 2 to 6 Gy; the total dose was 50 to 70 Gy. The short-term efficacy and prognosis were observed and analyzed. The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis. Multivariate analysis was performed using the Cox regression model. ResultsThe complete remission, partial remission, stable disease, and disease progression rates were 3.57%, 32.14%, 53.57%, and 10.72%, respectively. The overall median progression-free survival (PFS) time was 6.43 months, and the median overall survival (OS) time was 11.43 months. The 1- and 2-year survival rates were 46.79% and 25.23%, respectively. Univariate analysis showed tumor response rate was an independent prognostic factor for PFS. The Cox proportional hazard model suggested the tumor response rate and prescribed dose were the independent prognostic factors for PFS. In addition, the independent prognostic factors for OS included tumor response rate, tumor diameter, and tumor volume. The common acute radiotherapy toxicities included gastrointestinal discomfort, radiation-induced liver damage, and myelosuppression. ConclusionIMRT is a safe and effective option for the LHCC patients who are unsuitable for surgery or in the cases that other local therapies fail.
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With the development of radiotherapy techniques,the efficacy of radiotherapy for liver tumors has been improved,and radiothera-py can be considered as an alternative treatment for patients who are not suitable for surgery.The progress in liver tumor radiotherapy repor-ted in the 55th annual meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO)in 2013,particularly the efficacy and safety of stereotactic body radiation therapy for liver tumors,is reviewed.In the future,radiotherapy may be increasingly used as an ef-fective method in the treatment of liver tumors.The main studies reported at the meeting are sorted as follows in this article.
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To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.
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Objective To investigate the reproductive endocrine status of women with epilepsy at childbearing age and to systematically analyze the clinical features of reproductive endocrine disorders,especially polycystic ovarian syndrome (PCOS),to facilitate early detection and timely intervention.Methods In this study,scoring of anthropometry and physical signs,menstrul assessment,examination of sex hormone and pelvic ultrasound in women with epilepsy at childbearing age were performed,and the data such as overweight,central obesity,oligo/amenorrhea,luteinizing hormone (LH)/follicule-stimulating hormone (FSH),hyperandrogenism and polycystic ovary (PCO) were collected. The characteristics of their reproductive endocrine hormone disorders were analyzed statistically. Results The age of these patients was (22. 5 ± 7.0 ) years,and women younger than 30 years old and at their peak fertility accounted for 84. 89%. The prevalence rate of PCOS in women with epilepsy at childbearing age (12. 75% ) was significantly higher than that of ordinary women at childbearing age (7.2%) in China.Highly specific indicators for PCOS were hyperandrogenism (100%),LH/FSH ＞ 2 (93%) and oligo/amenorrhea (90%),whilst the highly sensitive indicators for PCOS were PCO (92%), oligo/amenorrhea (85%) and hyperandrogenism (54%). This study revealed statistically significant difference in LH,LH/FSH and testosterone (T) between PCOS group (LH: (10.24 ± 6.92) IU/L; LH/FSH;(2.20 ± 1.16);T: ( 1.07 ± 0. 35) ng/ml) and non-PCOS group ( LH: (4. 16 ± 2.62 ) IU/L; LH/FSH:( 0. 87 ± 0. 56 );T: (0. 46 ±0. 25) ng/ml,t = -3. 899,-4. 240 and -4. 918 respectively,all P ＜0. 01 ). Conclusions Hormone indices are objective indicators for the diagnosis of PCOS. In clinical practice,attention should be paid to height,weight,abodominal circumference,menstrul history and ultrasound examination of the ovary in women with epilepsy.When reproductive endocrine hormone disorders are suspected from clinical features,the sex hormones (T,LH,and FSH ) should be checked to allow timely detection and early interventions.
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[Objective]This study was designed to identify the risk factors related with reproductive endocrinology disorder in Chinese women of child-bearing age with epilepsy.[Methods]The clinical data of 102 women with epilepsy were collected.The patient were grouped according to seven aspects(seizure onset age,seizure type,seizure frequency,duration of epilepsy,AED type,age of start AED therapy and duration of therapy)and the contribution of these factors in development of PCOS and its components were analyzed.[Results]The incidence of hyperandrogenemia in the patients with an early onset age(≤14 years old)was higher than the ones with an onset age＞14 years old.Onset age≤14 was the risk factor of hyperandrogenemia in logistic regression analysis.The incidence of a/oligomenorrhea,polycystic ovaries,hyperandrogenemia and PCOS in the valproate-treated women were 40.63%,50.00%,15.65%,and 34.38%,respectively,which were higher than the no-therapy group and nonvalproate treated group.Valproate therapy was the risk factor of PCOS and its components.[Conclusion]Valproate therapy was the risk factor of PCOS and its components in Chinese women of child-bearing age with epilepsy.Onset age≤14 was the risk factor of hyperandrogenemia.