Amyloid Neuropathies, Familial ; genetics ; Cardiomyopathies ; Humans ; Mutation

Objective To observe the effects oftelmisartan (TEL) on learning and memory functions of animal models of Alzheimer's disease combined with hypertension.Methods Seventy male spontaneously hypertensive rats were randomly assigned into 7 groups:control group,sham-operated group,model group,low TEL group (1 mg/[kg· d]),high TEL group (10 mg/[kg· d]),low TEL+GW9662 group (Tel 1 mg/[kg·d]+GW 1 mg/[kg·d]),and high TEL+GW9662 group (Tel 10 mg/[kg·d],GW 10 mg/[kg·d],n=10);the lateral cerebral ventricle of rats in the later 5 groups were injected with beta-amyloid peptide 1-42 (Aβ1-42);rats in the sham-operated group were given the same volume of normal saline,and those in the control group did not give any treatment.The learning and memory abilities of these rats were detected by Morris Maze test;microglia level and casepase-3 expression were assessed by immunohistochemical stainning.Results Constant-bearing navigation indicated that as compared with the model group,the high TEL+GW9662 group,control group and sham-operated group had significantly shorten escape latency on the 3rd d of experiment (P＜0.05),and as compared with the model group,the low TEL group,high TEL group and high TEL+GW9662 group had significantly shorten latency (P＜0.05).Spatial probe test showed that the times of crossing the platform,target quadrant residence time in the low TEL group,high TEL group and high TEL+GW9662 group were significantly larger/longer than those in the model group (P＜0.05).The casepase-3 expression and microglia level in the CA1 area of model group were significantly higher than those in the control group (P＜0.05);The Ibal and caspase-3 expressions in the low TEL group,high TEL group and high TEL+GW9662 group were significantly weaker than those in the model group (P＜0.05).Conclusion TEL has preventive effect on cognitive decline in rat models of Alzheimer's disease complicated with hypertension,and can be restrained by GW9662,which suggests that these benefits might be partly resulted from PPAR-γ activation and intracranial infection inhibitation.

OBJECTIVETo detect pathogenic mutations in Marfan syndrome (MFS) using an Ion Torrent Personal Genome Machine (PGM) and to validate the result of targeted next-generation semiconductor sequencing for the diagnosis of genetic disorders.

METHODSPeripheral blood samples were collected from three MFS patients and a normal control with informed consent. Genomic DNA was isolated by standard method and then subjected to targeted sequencing using an Ion Ampliseq(TM) Inherited Disease Panel. Three multiplex PCR reactions were carried out to amplify the coding exons of 328 genes including FBN1, TGFBR1 and TGFBR2. DNA fragments from different samples were ligated with barcoded sequencing adaptors. Template preparation and emulsion PCR, and Ion Sphere Particles enrichment were carried out using an Ion One Touch system. The ion sphere particles were sequenced on a 318 chip using the PGM platform. Data from the PGM runs were processed using an Ion Torrent Suite 3.2 software to generate sequence reads. After sequence alignment and extraction of SNPs and indels, all the variants were filtered against dbSNP137. DNA sequences were visualized with an Integrated Genomics Viewer. The most likely disease-causing variants were analyzed by Sanger sequencing.

RESULTSThe PGM sequencing has yielded an output of 855.80 Mb, with a > 100 × median sequencing depth and a coverage of > 98% for the targeted regions in all the four samples. After data analysis and database filtering, one known missense mutation (p.E1811K) and two novel premature termination mutations (p.E2264X and p.L871FfsX23) in the FBN1 gene were identified in the three MFS patients. All mutations were verified by conventional Sanger sequencing.

CONCLUSIONPathogenic FBN1 mutations have been identified in all patients with MFS, indicating that the targeted next-generation sequencing on the PGM sequencers can be applied for accurate and high-throughput testing of genetic disorders.

Base Sequence ; Computational Biology ; Fibrillin-1 ; Fibrillins ; Genomics ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Marfan Syndrome ; diagnosis ; genetics ; Microfilament Proteins ; genetics ; Mutation ; Semiconductors

OBJECTIVES: To investigate the clinical characteristics of patients with listeriosis and to provide a basis for diagnosis, treatment, prevention and control of hospital infection. METHODS: A total of 10 inpatients, who suffered from the listeriosis in Xiangya Hospital, Central South University from January 2013 to June 2019, were retrospectively collected for this study. The characteristics of the patients' age, gander, basic information, case type, clinical manifestations, first consultation department, days of diagnosis, infection indicator, specimen type, results of drug sensitivity, treatment plan, hospital infection or not, outcome, follow-up data were analyzed. RESULTS: Two cases were pregnant women and other were non-pregnant adults among 10 patients with listeriosis. Among them, there were 3 cases with hospital acquired infection. The age of patient onset was 27-71 years old, and the time from onset to diagnosis was 5-36 days. Five cases had fever, and other 5 cases had not fever. There were headache, fatigue, local pain, and other specialized symptoms in the 10 patients.The white blood cell count,the neutrophil ratio, the inflammatory index C-reactive protein, the procalcitonin were all increased, and the erythrocyte sedimentation was accelerated in the 10 patients.All the patients were sensitive to ampicillin, penicillin G, meropenem, and compound sinomine. CONCLUSIONS Listeriosis often affects the patients with low immunity, which often leads to misdiagnosis or missed diagnosis in clinic.So early prevention, early diagnosis, and early treatment can reduce mortality; it is important for departments of nosocomial infection management to manage patients' diet for avoiding outbreaks of listeriosis in hospital.
Adult ; Aged ; Female ; Humans ; Listeria monocytogenes ; Listeriosis/epidemiology* ; Meropenem ; Middle Aged ; Pregnancy ; Pregnancy Complications, Infectious ; Retrospective Studies