MicroRNAs (miRNAs/miRs) are involved in post-transcriptional gene regulation and aberrant expression of miRNAs has been widely detected in various human diseases. The aim of the present study was to examine the serum levels of miR-133b in patients with Alzheimer's disease (AD), and to explore its diagnostic value and neuroprotective role in AD. Reverse transcription-quantitative PCR was applied to analyze the serum levels of miR-133b in 105 AD patients and 98 healthy controls. A cell model of AD was established by treating SH-SY5Y cells with amyloid β (Aβ)25-35, and the resulting effect on miR-133b expression was determined. Cell viability and apoptosis were also measured. A dual-luciferase assay was used to validate a target gene of miR-133b. Receiver operating characteristic (ROC) curve analysis was also applied to assess the specificity and sensitivity of miR-133b to diagnose AD. The results indicated that the serum levels of miR-133b were significantly downregulated in AD patients and SH-SY5Y cells treated with Aβ25-35 (all P<0.001). A positive correlation between the serum levels of miR-133b and the Mini-Mental State Examination score of AD patients was determined (r=0.8814, P<0.001). The area under the ROC curve for miR-133b regarding the diagnosis of AD was 0.907, with a sensitivity of 90.8% and specificity of 74.3% at the cutoff value of 1.70. Overexpression of miR-133b significantly attenuated the Aβ25-35-induced inhibition of cell viability (P<0.01) and induction of cell apoptosis (P<0.01). The luciferase reporter assay demonstrated that epidermal growth factor receptor (EGFR) is a target gene of miR-133b. In conclusion, miR-133b may serve as a novel diagnostic biomarker for AD and it may have a neuroprotective role in AD and targets EGFR.
Turner syndrome (TS), a disorder caused by the congenital absence of one of the 2 X chromosomes in female humans, provides a valuable human "knockout model" for studying the functions of the X chromosome. At present, it remains unknown whether and how the loss of the X chromosome influences intrinsic functional connectivity (FC), a fundamental phenotype of the human brain. To address this, we performed resting-state functional magnetic resonance imaging and specific cognitive assessments on 22 TS patients and 17 age-matched control girls. A novel data-driven approach was applied to identify the disrupted patterns of intrinsic FC in TS. The TS girls exhibited significantly reduced whole-brain FC strength within the bilateral postcentral gyrus/intraparietal sulcus, angular gyrus, and cuneus and the right cerebellum. Furthermore, a specific functional subnetwork was identified in which the intrinsic FC between nodes was mostly reduced in TS patients. Particularly, this subnetwork is composed of 3 functional modules, and the disruption of intrinsic FC within one of these modules was associated with the deficits of TS patients in math-related cognition. Taken together, these findings provide novel insight into how the X chromosome affects the human brain and cognition, and emphasize an important role of X-linked genes in intrinsic neural coupling.
Purpose This meta-analysis systematically evaluated the efficacy and safety of anti-PD-1/PD-L1 antibodies for pretreated advanced or metastatic nonsmall cell lung cancer (NSCLC) and investigated the correlation between PD-L1 expression levels and effectiveness of anti-PD-1/PD-L1 antibody. Methods The methodology was based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) and the Cochrane Collaboration guidelines. Results Our research included five randomized-controlled trials involving 3,025 patients. We compared anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, and atezolizumab) with docetaxel in pretreated patients with advanced or metastatic NSCLC. The pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was 0.69 (95%CI: 0.63-0.75, P<0.0001, and Ph=0.67) and 0.87 (95%CI: 0.81-0.94, P=0.0004, and Ph=0.11), respectively. Meanwhile, the pooled risk ratio (RR) for objective response rate (ORR) was 1.53 (95% CI: 1.16-2.01, P=0.003, and Ph=0.03) in all patients. Subgroup analyses showed that anti-PD-1/PD-L1 treatment significantly improved OS in patients with PD-L1 expression at any level, even in patients with PD-L1<1%. The RR for occurrence of grades 3 to 5 treatment-related adverse effects was 0.23 (95% CI: 0.15–0.36, and P<0.001). Conclusion OS, PFS, and ORR were significantly more improved for patients treated with anti-PD-1/PD-L1 antibodies than for those treated with docetaxel. Anti-PD-1/PD-L1 therapy resulted in longer OS than docetaxel, regardless of PD-L1 expression; however, higher PD-L1 levels were likely to correlate with better outcome. Anti-PD-1/PD-L1 antibodies also had a better safety profile than docetaxel.
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