Accumulating evidence indicates that abnormal deposition of amyloid-b (Ab) peptide in the brain is responsible for endothelial cell damage and consequently leads to bloodbrain barrier (BBB) leakage. However, the mechanisms underlying BBB disruption are not well described. We employed an monolayer BBB model comprising bEnd.3 cell and found that BBB leakage was induced by treatment with Ab 1-42, and the levels of tight junction (TJ) scaffold proteins (ZO-1, Claudin-5, and Occludin) were decreased. Through comparisons of the effects of the different components of Ab 1-42 , including monomer (Ab 1-42 -Mono), oligomer (Ab 1-42 -Oligo), and fibril (Ab 1-42 -Fibril), our data confirmed that Ab 1-42 -Oligo is likely to be the most important damage factor that results in TJ damage and BBB leakage in Alzheimer's disease. We found that the incubation of bEnd.3 cells with Ab 1-42 significantly up-regulated the level of receptor for advanced glycation end-products (RAGE). Co-incubation of a polyclonal antibody to RAGE and Ab 1-42 -Oligo in bEnd.3 cells blocked RAGE suppression of Ab 1-42 -Oligo-induced alterations in TJ scaffold proteins and reversed Ab 1-42 -Oligoinduced up-regulation of RAGE, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, we found that these effects induced by Ab 1-42 -Oligo treatment were effectively suppressed by knockdown of RAGE using small interfering RNA (siRNA) transfection. We also found that GM 6001, a broad-spectrum MMP inhibitor, partially reversed the Ab 1-42 -Oligo-induced inhibitor effects in bEnd.3 cells. Thus, these

Background: To perform a systematic review and meta-analysis evaluating the perioperative, functional, and oncological outcomes and cost of robot-assisted radical prostatectomy (RARP), or laparoscopic radical prostatectomy (LRP) comparing with open radical prostatectomy (ORP) in men with clinically localized prostate cancer through all prospective comparative studies. Methods: A comprehensive literature search was performed in August 2018 using the Pubmed, Medline, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) and prospective studies including patients with clinically localized prostate cancer were eligible for study inclusion. Cumulative analysis was conducted using Review Manager v. 5.3 software. Results: Two RCTs and 9 prospective studies were included in this systematic review. There were no significant differences between RARP/LRP and ORP in overall complication rate, major complication rate, overall positive surgical margin (PSM) rate, ≤pT2 tumor PSM rate, ≥pT3 tumor PSM rate. Moreover, RARP/LRP and ORP showed similarity in biochemical recurrence (BCR) rate at 3, 12, 24 months postoperatively. Urinary continence and erectile function at 12 months postoperatively between RARP and ORP are also comparable. RARP/LRP were associated with significantly lower estimated blood loss [mean difference (MD) −749.67, 95% CI −1038.52 to −460.82, P = .001], lower transfusion rate (OR 0.17, 95% CI 0.10 to 0.30, P < .001) and less hospitalization duration (MD −1.18, 95% CI −2.18 to −0.19, P = .02). And RARP/LRP required more operative time (MD 50.02, 95% CI 6.50 to 93.55, P = .02) and cost. Conclusion: RARP/LRP is associated with lower blood loss, transfusion rate and less hospitalization duration. The available data were insufficient to prove the superiority of any surgical approach in terms of postoperative complications, functional and oncologic outcomes.

Purpose Epidermal growth factor receptor (EGFR) mutation-positive (EGFRmut+) non-small cell lung cancer (NSCLC) may be a unique orphan disease. Previous studies suggested that the telomerase reverse transcriptase (TERT) gene polymorphism is associated with demographic and clinical features strongly associated with EGFR mutations, e.g. adenocarcinoma histology, never-smoking history and female gender. We aim to test the association between TERT polymorphism and EGFRmut+ NSCLC. Experimental Design We conducted a genetic association study in Chinese NSCLC patients (n=714) and healthy controls (n=2,520), between the rs2736100 polymorphism and EGFRmut+ NSCLC. We further tested the association between the EGFR mutation status and mean leukocyte telomere length (LTL). The potential function of rs2736100 in lung epithelial cells was also explored. Results The rs2736100-C allele was significantly associated with EGFRmut+ NSCLC (OR=1.52, 95%CI=1.28–1.80, p=1.6×10−6) but not EGFRmut− NSCLC (OR=1.07, 95%CI=0.92–1.24, p=0.4). While NSCLC patients as a whole have significantly longer LTL compared to healthy controls (p≤10−13), the EGFRmut+ patients have even longer LTL compared to EGFRmut-patients (p=0.008). Meanwhile, rs2736100 was significantly associated with TERT mRNA expression in both normal and tumor lung tissues. All results remained significant after controlling for age, gender, smoking status and histology (p<0.05 for all tests). Moreover, the rs2736100 DNA sequence has an allele-specific affinity to nuclear proteins extracted from lung epithelial cells, which led to an altered enhancer activity of the sequence in vitro. Conclusion Our study suggests that telomerase and telomere function may be essential for carcinogenesis of EGFRmut+ NSCLC. Further investigation for the underlying mechanism is warranted.

A recent genome-wide association study has identified an association between leukocyte telomere length (LTL) and a locus at 3q26 that includes TERC. In order to evaluate the effects of the SNPs rs12696304 and rs16847897 near TERC in the population of mainland China, we conducted an association study of LTL focusing on these two candidate SNPs in a sample of 4016 Chinese Han individuals. Multiple linear regression analyses were performed to evaluate the association of LTL with each SNP adjusted for age, gender and diabetes status. In the study, we confirmed the association of SNP rs12696304 and rs16847897 near TERC with LTL in the Chinese Han population (PB4.5Â10 À3 and 9.5Â10 À5 , respectively). Each copy of the major allele of rs12696304 and rs16847897 was associated with a shorter mean telomere length of 0.024 and 0.031 T/S respectively, which is equivalent to about 3 and 4 years of average age-related telomere attrition. Our short report confirmed the effects of SNPs near TERC on LTL in the Chinese Han population for the first time. Keywords: Chinese population; TERC; leukocyte telomere length INTRODUCTIONTelomeres are structures at the ends of eukaryotic chromosomes, which are made up of a repetitive sequence and which has a major role in genomic stability. Telomere dysregulation can lead to cell death, cell senescence, or abnormal cell proliferation. 1 In humans, leukocyte telomere length (LTL) is getting shorter progressively with age, and is frequently reported to be relatively shorter in aging-related diseases: such as Alzheimer's disease 2 and vascular dementia. 3 Telomere length varies between individuals of the same age, and is found to be inheritable in quantitative-trait linkage analyses of sib pairs. 4,5 Quantitative trait locus studies have mapped putative loci for telomere length to human chromosomes 3p26.1, 10q26.13, 12q12.22 and 14q23.2. [5][6][7] Telomerase is a large, mainly uncharacterized, RNA-protein complex that is responsible for the de novo synthesis and maintenance of telomere ends. TERC is a main component of telomerase, which serves as a template for addition of multiple 6 bp (TTAGGG) telomere repeats. A recent genome-wide association study (GWAS) identified association of common variants near TERC (on 3q26) with telomere length in two large European cohorts of 2917 individuals, followed by replication in three further European cohorts of 9492 individuals. 8 The strongest associations with LTL were observed for SNP rs12696304 and rs16847897 near TERC on 3q26, and the association signals across the 3q26 locus between rs12696304 and rs16847897 are located toward opposite ends of an B87 kb region showing significant

Our findings suggest that BDNF levels may serve as a potential differential diagnostic biomarker for bipolar disorder in a patient's first depressive episode.

Our research demonstrates association between shorter LTL and T2D in a population from mainland China. Our study suggests that shorter LTL might be associated with T2D in a manner independent of smoking and drinking habits or the time of T2D onset time.

To compare the efficacy and safety of augmenting paroxetine with risperidone, buspirone, valproate, trazodone, or thyroid hormone in patients with treatment-resistant depression (TRD), 225 patients with retrospectively and/or prospectively identified stage II TRD were randomly assigned to receive an 8-week treatment of paroxetine 20 mg/d augmented with risperidone 2 mg/d (n = 45), sodium valproate 600 mg/d (n = 39), buspirone 30 mg/d (n = 46), trazodone 100 mg/d (n = 47), or thyroid hormone 80 mg/d (n = 48). The primary outcome was the remission rate defined as the 17-item Hamilton Rating Scale for Depression score of 7 or less at the end of study. Secondary outcomes included remission rate based on the Self-rating Depression Scale score of 50 or less at the end of study, response rate based on 17-item Hamilton Rating Scale for Depression total score of 50% improvement or greater from baseline, and the change in scores of Clinical Global Impression-Improvement scale, the Short Form 36 Health Survey, and the Life Satisfaction Rating Scale. The remission rates were 26.7% for risperidone, 48.7% for valproate, 32.6% for buspirone, 42.6% for trazodone, and 37.5% for thyroid hormone. There was no statistical significance among treatment arms in remission rates, secondary outcome measures, and adverse events. Risperidone, valproate, buspirone, trazodone, or thyroid hormone augmentation to paroxetine 20 mg/d was effective and well tolerated in Chinese patients with TRD. Large-sample studies are warranted to support or refute these findings.

Leukocyte telomere length (LTL) is a predictor of aging and a number of age-related diseases. We performed genome-wide association studies of mean LTL in 2632 individuals,with a two-stage replication in 3917 individuals from Chinese populations. To further validate our findings, we get the results of 696 samples from a cohort of European ancestry. We identified two loci associated with LTL that map in telomerase reverse transcriptase (TERT; rs2736100, P = 1.93×10−5) on chromosome 5p15.33 and near keratin 80 (KRT80; rs17653722, P = 6.96×10−6) on 12q13.13. In Chinese population each C allele of rs2736100 and T allele of rs17653722 was associated with a longer mean telomere length of 0.026 and 0.059 T/S, respectively, equivalent to about 3 and 7 years of average age-related telomere attrition. Our findings provide new insights into telomere regulatory mechanism and even pathogenesis of age-related diseases.