Changes of mRNA N6-methyladenosine methylation in blood of patients with Alzheimer's disease / 中华行为医学与脑科学杂志

Objective:To explore the changes of mRNA N6-methyladenosine methylation level and methyltransferase-like 3 (METTL3) and demethylase fat mass and obesity-associated (FTO) in the blood of patients with Alzheimer's disease (AD) compared with normal controls.Methods:From January 2020 to June 2021, totally 40 AD patients treated in the outpatient and inpatient department of Neurology of the Affiliated Hospital of Jining Medical University were selected as the patient group, and 40 healthy volunteers as the control group. The blood samples were collected to extract plasma and peripheral blood mononuclear cells for enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real-time PCR (qPCR) and m6A methylation quantification experiments respectively to detect the methylation levels of METTL3, FTO and m6A. The data were analyzed by SPSS 23.0 statistical software for t-test. Results:The plasma concentrations of METTL3 and FTO protein in AD group were lower than those in control group (METTL3: (22.33±3.01)ng/mL, (25.63±1.70)ng/mL, t=6.055, P<0.01; FTO: (63.51±4.95)pg/mL, (69.60±4.60)pg/mL, ( t=5.704, P<0.01). The band gray values of METTL3 and FTO protein in blood cells in AD group were lower than those in control group (METTL3: 0.399 5±0.028 7, 0.676 6±0.053 3, t=7.935, P=0.001; FTO: 0.439 4±0.017 8, 0.782 6±0.087 6, t=6.652, P=0.003). The expression levels of METTL3 and FTO in blood cell RNA in AD group were lower than those in control group (METTL3: 0.387 8±0.020 3, 1.010 0±0.177 0, t=6.041, P=0.004; FTO: 0.442 8±0.037 1, 1.003 0±0.090 4, t=9.931, P=0.001). The levels of m6A in blood cell RNA in AD group were lower than those in control group((0.000 571±0.000 167)%, (0.002 514±0.001 284)%, t=6.041, P=0.004). Conclusion:The levels of METL3, FTO and m6A methylation are down-regulated in the plasma and peripheral blood mononuclear cells of patients with AD, indicating that there is a certain association between mRNA N6-methyladenosine methylation and AD.

A Chinese pedigree with early-onset familial Alzheimer′s disease caused by presenilin 1 p.G378E mutation / 中华神经科杂志

Objective To investigate the phenotypes and genetics of an early-onset familial Alzheimer′s disease ( EO-FAD ) family.Methods The clinical manifestations , brain MRI results and neuropathological findings of the proband and pedigree members of the EO -FAD family were evaluated. Autopsy was performed in the proband . Results Fifteen members of this family had a presenilin 1 (PSEN1) p.G378E mutation and nine of them had clinical manifestations or the MRI changes of EO -FAD. Neuropathological findings from autopsy of the proband disclosed moderate cortical atrophy throughout the brain, especially in frontal lobe and temporal lobe .Neuronal loss with gliosis was observed in the cortices of the frontal, temporal and occipital lobes , as well as in parahippocampal gyrus .Numerous senile plaques and neurofibrillary tangles were present in the cerebral cortex .The proband′s younger sister showed similar clinical presentations and MRI changes , and other members of this family demonstrated progressive memory loss.Conclusion A p.G378E mutation in the PSENl gene was identified in a Chinese EO-FAD pedigree.

Comparison of open thoracic drainage and conventional thoracic drainage tube applicated in patients after pneumonectomy / 中国基层医药

Objective To compare the clinical effects between open thoracic drainage and conventional thoracic drainage tube applicated in patients after pneumonectomy.Methods 120 cases after pneumonectomy were selected as research subjects,and they were randomly divided into two groups according to the digital table,60 cases in each group.The control group was given conventional thoracic drainage tube,while the observation group received open thoracic drainage,The clinical effects were compared between the two groups.Results The length of hospital stay,total drainage and retention time of drainage tube in the observation group were significantly higher than those inthe control group,the overall incidence rate of complications in the observation group was 13.33％,which was lower than 23.33％ in the control group,but there were no statistically significant differences (t =1.60,1.97,0.72,x2 =2.00,all P ＞ 0.05).Conclusion Open thoracic drainage has similar clinical effect with conventional thoracic drainage tube on patients after pneumonectomy,it is worthy to be promoted clinically.

Serum microRNA test in one Chinese early-onset familial Alzheimer's disease and preliminary analysis / 中华行为医学与脑科学杂志

Objective To determine the expression profile of serum microRNAs(miRNAs) in early-onset familial Alzheimer's disease (EO-FAD) patients. methods miRNA microarrays were performed to detect the expression profile of serum miRNAs in 2 cases of EO-FAD patients,2 cases of EO-FAD carriers and 2 cases of normal controls.Preliminary bioinformatic analysis was conducted. Result sIt was found that 21 miRNAs were up-regulated and 22 miRNAs were down-regulated in serum of EO-FAD patients,the differences were statistically significant(P<0.05).miR-5704(P=0.0002),miR-4639-3p(P=0.0195),miR-107(P=0.0204) were markedly up-regulated,miR-5572(P=0.0008),miR-204-3p(P=0.0014),miR-542-5p(P=0.0106) and miR-155-5p(P=0.0240) were markedly down-regulated.Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the dysregulated miRNAs may be involved in the mechanism of EO-FAD by affecting neurotrophin signaling pathway.Conclusion miR-5704,miR-4639-3p,miR-107,miR-5572,miR-204-3p,miR-542-5p and miR-155-5p may be used as potential biomarkers of EO-FAD,and involved in the mechanism of EO-FAD by affecting neurotrophin signaling pathway.