Objective To investigate the effect of α7nAchR gene 713T>C mutation on the cognitive function and Aβ expression in Alzheimer′s disease(AD)mice.Methods Twenty APPSwe transgenic APPa7KO mice(6 months old,α7nAchR gene knockout)were divided into the mutation type group and wild type group according to the random number table method,10 cases in each group.The mutation type and wild type of AVV-α7nAchR cDNA were respectively injected by lateral ventricle,once per month,for 6 times.The change of cognitive function in mice was examined by Morris water maze.The ELISA method was used to detect Aβ 40 and Aβ 42 expression levels.The Aβ plaque deposit situation was detected by the immunochemical method.Results Compared with the mice in the wild type group,the escape latency and the time of first time to find the platform of the mice in the mutation type group were significantly extended,while Hippocampal Aβ40 and Aβ42 expression levels were significantly increased,the difference was statistically significant(P＜0.05).Conclusion α7nAchR gene 713T>C mutation aggravates the cognitive function impairments in AD mice and hippocampal neuron Aβ expression level.

Bacterial Proteins ; metabolism ; Carbon-Sulfur Lyases ; metabolism ; Mouth ; microbiology ; Quorum Sensing ; Signal Transduction

This study investigated a nano drug delivery system built by one sort of modified trimethyl chitosan (TMC). The TMC was modified by cRGDyk, ligand of integrin receptor avβ3. Single factor screening was used to optimize the prescription in which the particle sizes of TMC nanoparticle (TMC NPs) and cRGDyk modified TMC nanoparticle (C-TMC NPs) were (240.3 ± 4.2) nm and (259.5 ± 3.3) nm. Electric potential of those two nanoparticles were (33.5 ± 0.8) mV and (25.7 ± 1.6) mV. Encapsulation efficiencies were (76.0 ± 2.2) % and (74.4 ± 2.0) %. Drug loading efficacies were (50.1 ± 2.1) % and (26.1 ± 1.0) %. Then the cellular uptake, uptake mechanism and transport efficacy of TMC NPs and C-TMC NPs were investigated using Caco-2 cell line. The uptake rate and accumulating drug transit dose of C-TMC NPs were 1.98 and 2.84 times higher than TMC NPs, separately. Mechanism investigations revealed that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis were involved in the intercellular uptake of both TMC NPs and C-TMC NPs. What is more, free cRGDyk could remarkably inhibit the uptake of C-TMC NPs.
Biological Transport ; Caco-2 Cells ; Caveolae ; Chitosan ; chemistry ; Clathrin ; Endocytosis ; Humans ; Integrin alphaVbeta3 ; chemistry ; Nanoparticles ; Particle Size ; Pinocytosis

ObjectiveTo investigate the characteristic parameters and variation of acoustic startle reflex (ASR) and conditioning response (CR)during the acquisition of delay-trace eyeblink conditioning.Methods15healthy Kunming mice were randomly divided into 3 groups:single-task DEBC group ( n =5 ) ; single-task TEBC group ( n =5) ; dual delay/trace group ( n =5).Three groups received paired training of tone conditioned stimulus(CS)in different audio frequency (TEBC groups:2KHz; DEBC group:1KHz) and a 100 ms comeal oxygenpuff unconditioned stimulus(US).Then observed the characteristic parameters of ASR and CR.ResultsAfter pairing training for 10 days,ASR rate( ASR％ ) of single-task groups ( 10th day (38.00 ± 8.64) ％ and (38.55 ±12.41 ) ％ respectively,time effect:F =4.574,P =0.008 ; group effect:F =2.021,P =0.193 ) and dual delaytrace group ( 10th day (47.95 ± 14.23 ) ％ and (62.01 ± 9.03 ) ％ respectively,time effect:F =5,547 P =0.013 ;group effect:F =0.738,P =0.415) changed significantly with the following training but between single-task groups or dual delay-trace group.CR rate ( CR％ ) of single-task groups ( 10th day were (45.4 ± 5.39) ％ and (65.6 ± 6.77) ％ respectively,time effect:F =9.558,P =0.000 ; group effect:F =5.117,P =0.054 ) and dual delay/trace group ( 10th day (57.66 ± 4.34) ％ and (77.35 ± 7.36) ％ respectively,time effect:F =7.750,P =0.002 ;group effect:F=1.449,P=0.263 ) showed obvious change with the following training but between singletask groups or dual delay-trace group.Peak amplitude of single-task DEBC group ( time effect F =2.679,P =0.017 ) and dual delay-trace group ( F=3.452,P=0.034 ) had increased significantly with the following training.Peak latency showed no obvious change.ConclusionDual delay-trace conditioning procedure of classical eyeblink conditioning and single-task can be successfully established in Kunming mice.Although there are some variations,those can be controled and be weaken effect of them by taking targeted measures.

ObjectiveTo investigate the association of nonalcoholic fatty liver disease (NAFLD) with insulin resistance and dyslipidemia in patients with type 2 diabetes mellitus,and to analyze the risk factors.Methods A total of 200 patients with type 2 diabetes mellitus including 99 with NAFLD and 101 without NAFLD were recruited.Height,weight,waist circumference,hip circumference,liver enzymes,blood lipids,fasting and postprandial blood glucose,insulin,C-peptide,and HbA1C levels were detected.Body mass index ( BMI),waist-hip ratio( WHR),and improved insulin and C-peptide index(HOMA-C-peptide) were calculated and compared between two groups.ResultsCompared with non-NAFLD group,weight,BMI,waist circumference,hip circumference,alanine aminotransferase ( ALT),aspartate aminotransferase,triglyceride ( TG ),total cholesterol ( TC ),low density lipoprotein-cholesterol(LDL-C) were significantly higher in NAFLD group( all P＜0.01 ),while age,duration,and high density lipoprotein-cholesterol were lower( all P＜0.05 ).The incidence of combined hyperlipidemia,especially hypertriglyceridemia,was significantly higher in NAFLD group( P＜0.01 ).Fasting and postprandial 1 h blood glucose [ ( 2.07 ±0.36 vs 1.83 ±0.43 ) mmol/L,( 14.04 ± 3.96 vs 12.59 ± 3.90 ) mmol/L ],fasting and postprandial 1 h Cpeptide [ (2.79± 1.15 vs 2.08±1.29 ) ng/ml,( 1.33 ±0.45 vs 1.12±0.54) ng/ml ],HbA1C [ (2.09±0.33 vs 1.96±0.28) ％ ],and HOMA-C-peptide index were significantly increased in NAFLD group ( P ＜ 0.05 or P ＜ 0.01 ).Logistic analysis showed that TG,BMI,and ALT were the major risk factors of NAFLD in type 2 diabetes mellitus( P＜0.05 or P＜0.01 ).ConclusionTriglyceridemia,obesity,and raised ALT level were significantly associated with an increased risk of NAFLD in patients with type 2 diabetes mellitus.

Air Pollutants, Occupational ; chemistry ; Indium ; analysis ; Mass Spectrometry ; methods ; Occupational Exposure ; Spectrum Analysis ; methods ; Workplace

Objective:To analyze the association between the types of response to head-up tilt test (HUTT) and levels of various vitamins in children and adolescents with orthostatic intolerance.Methods:Sixty-five cases of children and adolescents 35 males and 30 females aged 5-14 (10.5±2.0) years old who complained orthostatic intolerance symptoms, including syncope, dizziness, headache, and chest tightness, in Children′s Medical Center, the Se-cond Xiangya Hospital, Central South University between November 2018 and April 2019, were enrolled.By comprehensive history, physical examination, and necessary laboratory testing, heart, cerebrovascular and other system diseases were excluded.According to HUTT result, these patients were divided into 2 groups, namely negative HUTT group and positive HUTT group.The serum levels of vitamin A 1, B 1, B 2, B 6, B 9, B 12, C, and E were compared between the 2 groups.Continuous data were analyzed by conducting t-test and categorical data were analyzed by performing χ2 test. Results:(1) There were 32 cases (18 males and 14 females) in negative HUTT group and 33 cases (17 males and 16 females) in positive HUTT groups, with 28 cases of vaso vagal syncope and 5 cases of postural tachycardia syndrome.There were no significant differences in age, gender ratio, and body mass index between the negative HUTT group and positive HUTT group.(2) The serum level of vitamin B 1 of positive HUTT group was lower than that of negative HUTT group [(77.43±16.70) nmol/L vs.(88.56±18.98) nmol/L, t=-2.513, P<0.05], while the levels of vitamin A 1, B 2, B 6, B 9, B 12, C, and E had no significant differences between the two groups (all P>0.05). Conclusions:Patients with positive responses to HUTT relatively lacked vitamin B 1, suggesting the role of vitamin B 1 in the pathophysiological process of neurally mediated syncope.

Background A multitude of studies reported statins prevent the myocardial hypertrophy induced by pressure overload,but the mechanism is unclear.Objective To study the protective effect of atorvastatin on the myocardial hypertrophy caused by pressure overload and it's anti-inflammation effect.Methods Forty Wistar rats were randomized to untreated group(n=10),atorvastatin group(2 mg/kg?d,by gavage,n=10),sham op- eration group(n=10)and control group(n=10).Ventricular hypertrophy model was achieved by surgical con- stricting the abdominal aorta.All rats were sacrificed 8 weeks after the operation and the heart weight to body ratio,left ventricular weight to body ratio,and the size of cardiomyocyte were determined.The expressions of interleukin 18(IL-18)and cardiotrophin 1(CT-1)in the cadiocyte were assessed by reverse transcription polymer- ase chain reaction(RT-PCR).Results Compared with control group,SBP in myocardial hypertrophy group was significantly increased(174?9 vs control 112?15 mmHg,P

Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; DNA Mutational Analysis ; Humans ; Lung Neoplasms ; genetics ; metabolism ; Mutation ; Polymerase Chain Reaction ; methods ; Receptor, Epidermal Growth Factor ; genetics

Based on the outpatient interview and literature review,the initial framework of the outpatient experience of human caring scale was formed with 9 dimensions of outpatient process.The research aim was to improve the scale by Delphi method.Sixteen experts in medical management,human caring or medical education were invited to evaluate the importance of the dimensions and items of the scale and provided some expertise via filling out the Delphi consultation questionnaires twice in the consulting round.In the first round,the recovery rate showing the experts' positivity was 80％;the coefficient of reliability (Cr) ascertaining the authority of the evaluation was 0.92;the mean and full mark ratios responding the concentration of the evaluation were 2.88-4.94 and 6.25％-93.75％ respectively;the coefficients of variation (CV) and the Kendall's W determining the concordance of the evaluation were 5.06％-52.15％ and 0.21-0.24 respectively.In the second round,the recovery rate was 93.75％;the Cr was 0.93;the mean was 3.93-4.93;the full mark ratios were 26.67％-93.33％;the Kendall's W was 0.14-0.31,the CV was 5.25％-23.61％.Via the two-round Delphi study,the scale that included 10 dimensions and 61 items has been improved.Ten dimensions are pre-hospital medical service,guidance,registration,waiting,diagnosis & treatment,paying,inspection & assay,medicine receiving,therapy/injection/transfusion and global evaluation.It was concluded that Chinese scholars have paid high attention to human caring and outpatient experience.The experts have given high agreements about the dimensions which were established with Chinese outpatient process.The dimensions are different from the similar researches about outpatient experience study.In the future,it is necessary to survey the outpatients to test the construct validity,internal consistency reliability and others of the scale to improve the scale.