OBJECTIVEThe present study investigated the effects of rapamycin on Aβ1-42-induced deficits in working memory and synaptic plasticity.

METHODSAfter bilateral hippocampal injection of Aβ1-42 and rapamycinin rats, spontaneous alternation in Y-maze and in vivo hippocampal long-term potentiation (LTP) of rats were recorded. All data were analized by two-way repeated measures analysis of variance (ANOVA).

RESULTS(Hippocampal injection of Aβ1-42 alone impaired working memory of rats; (2) Rapamycin did not affect working memory of rats, but alleviated Aβ1-42-induced working memory deficits, compared with Aβ1-42 alone group; (Aβ1-42 remarkably suppressed in vivo hippocampal LTP of fEPSPs in the CA1 region; (4) Pretreatment with rapamycin prevented Aβ1-42-induced suppression of LTP.

CONCLUSIONThese data indicates that rapamycin could protect against Aβ1-42-induced impairments in working memory and synaptic plasticity in rats.

Amyloid beta-Peptides ; adverse effects ; Animals ; Hippocampus ; drug effects ; Long-Term Potentiation ; Maze Learning ; Memory, Short-Term ; drug effects ; Neuronal Plasticity ; drug effects ; Peptide Fragments ; adverse effects ; Rats ; Sirolimus ; pharmacology

Health Personnel ; psychology ; Humans ; Logistic Models ; Multivariate Analysis ; Professional Competence ; statistics & numerical data ; Stress, Psychological ; epidemiology

The efficacy of conventional drug therapy for inflammatory bowel disease (IBD) is not satisfactory. As monoclonal antibody has been widely used and increasingly understood, biological agent therapy has been proved as ideal strategy in attaining mucosal healing, preventing complications, improving quality of life, and reducing hospitalization and surgical intervention. Furthermore, different randomized clinical trials assessed the efficacy in reducing the need for repeat surgery because of recurrence. Besides, biological agent therapy dose not increase most of postoperative side effects such as infection. However, adverse events of biological agents including serious infection, infusion reactions, delay type allergic reaction and myelosuppression should be paid attention to.
Biological Products ; adverse effects ; therapeutic use ; Humans ; Inflammatory Bowel Diseases ; drug therapy

Background Pupillary light reflex has been widely used in the diagnosis and evaluation of visual system and nervous system diseases.However,in animal experiments,functional evaluation of the visual system and nervous system needs more advanced technology and are affected by many factors.Objective This study was to explore the use of the dynamic pupillometer in evaluating pupillary light reflex and to discuss the influence of brightness of stimulate on relevant curve parameters in C57BL/6 mouse.Methods Ten healthy SPF male C57BL/6 mice were collected in this experiment.White light of five luminance levels (2,8,32,128,256 cd/m2) was used to stimulate the mice following a 2-hour dark adaptation.The stimulation was given at the 60-second intervals,for a duration of 100 ms at every stimulation.An infrared camera and video capture card were used to capture digital images during the measuring process in a scotopic environment,at a speed of 60 frames per second.Measuring outcome was saved in the*.AVI format.A software that was developed by our group was used to determine pupil diameter and output pupillary light reflex curve offline.Pupil initial diameter (R1),constriction amplitude (CA),constriction velocity (CV),latency (T1),time for maximum velocity (T2),time for maximum constriction (T3),time for maximun con-striction to 10.1％ R1 re-dilation (RT)and re-dilation velocity (RV)were assessed,and the correlations between luminosity and measuring parameters were analyzed using the Spearman rank correlation.The use of animals followed the Regulations for thd Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results R1 values showed no statistically significant difference among the 5 different luminosity groups(F=1.117,P=0.361).A positive linear correlation was found between stimulating luminosity and CA(r=0.508,P＜ 0.01),but negative correlations were seen between stimulating luminosity and CV or RV (r=-0.625,-0.609,P＜0.01).T1 and T2 values in the 5 different luminosity groups were not statistically significant (F =0.202,P =0.936 ; F =1.584,P =0.195).The different levels of stimulating luminosity showed positive linear correlations with T3 and RT values (r =0.791,0.609,P＜ 0.01).Conclusions The dynamic pupillometer can quantitatively measure the pupillary light reflex of C57BL/6 mice.The pupillary light reflex dynamic curve parameters of mouse were affected by stimulus luminosity levels.These outcomes offer a basis for the application of the dynamic pupillometer system for measuring pupillary light reflex in animal models.

Objective To report the experience of the arterial switch operation(ASO) for Taussig-Bing anomaly and late outcomes.Methods From January 2001 to December 2015,57 patients were underwent arterial switch operation for Taussig-Bing anomaly in Fudan university affiliated children's hospital cardiac center,Median age and weight at operation was 63(37.5-88.5)days, 4.1(3.4-5.0)kg, respectively.29 patients with Arch anomalies(50.9%), 23 patients with unusual coronaries(40.3%),according to have arch anomaly or not and surgery time, dividing the patients into two groups, group A(have, n=29)and group B(not have, n=28), earlier experience into group 1(2001-2008, n=27), later experience into group 2(2009-2015, n=30), respectively.Results The Mortality was12.3%, the mortality of group A and group B was 13.8%, 10.7%(P>0.05),group 1 and group 2 was 22.2%, 3.3%(P<0.05) respectively, follow up was complete in 47 patients with a mean follow-up of(6.2±3.5) years , three patients lost, there was no late mortality, the actual survival at 1, 5year was 87%, 87%, respectively.Reintervention was required in 10 patients(21.3%), the aorta-PA valve diameter ratio was a risk factor for reintervention(group A P=0.02, group B P=0.04) ,and 1,2,5year free of reintervention was 95.6%, 86.6%, 77.2%, respectively.Conclusion The ASO approach can be applied to Taussig-Bing anomaly with acceptable mortality , and it is the procedure of choice at our institution.One stage to repair TBA with aortic arch abnormalities did not influence outcomes.The aorta-PA valve diameter ratio<0.5 was a risk factor for reintervention.

Objective To investigate the diagnosis value of the tissue strain imaging in myocardial dysfunction in systemic lupus erythematosus (SLE). Methods Sixty-two patients and sixty controls underwent conventional and tissue Doppler echocardiography. Peak strain and strain rate value during systolic and diastolic phases as well as E/A, left ventricular fraction shortening (LVFS), left ventricular ejection fraction(LVEF) were measured in both SLE and the control groups. Results ①E/A,LVFS and LVEF did not differ between SLE patients and controls( P ＞0.05). The systolic peak strain and strain rate of SLE patients were lower than those of controls but without significant differences( P ＞0.05). ②The diastolic peak strain and strain rate of SLE patients were significantly lower than those of controls (P ＜0.01). ③ The diastolic peak strain and strain rate of antiheart antibody (AHA) positive patients were significantly lower than those of negative ones( P ＜0.05). Conclusions Strain and strain rate combining with AHA can sensitively detect myocardial dysfunction of SLE.

Hepatic encephalopathy is a common metabolic neuropsychiatric syndrome in the development of end-stage liver disease. Since the concept of intestinal-liver-brain axis was proposed, the relationship between the pathogenesis of hepatic encephalopathy and the gut microbiota has been a hot research topic. In recent years, studies have confirmed that gut microbiota is involved in and affects various pathological processes of hepatic encephalopathy. This article combines the latest research progress at home and abroad to elaborate on the research status of regulating gut microbiota and thus interfering with the pathological process of hepatic encephalopathy, hoping to provide new ideas and methods for the intervention of hepatic encephalopathy based on the regulation of gut microbiota.

OBJECTIVETo study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.

METHODSTM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.

RESULTSCFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.

CONCLUSIONThe CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.

Actins ; metabolism ; Animals ; Benzoates ; pharmacology ; Chloride Channels ; physiology ; Cystic Fibrosis Transmembrane Conductance Regulator ; antagonists & inhibitors ; Cytoskeleton ; drug effects ; Male ; Mice ; Sertoli Cells ; drug effects ; metabolism ; Spermatogenesis ; Thiazolidines ; pharmacology ; Time Factors

BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator (rt-PA) on the onset of acute cerebral infarction (ACI) at different time points of the first 6 hours.METHODS:A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI.RESULTS:National Institute of Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P>0.05) at 24 hours and 7 days after ACI. There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups (P>0.05).CONCLUSIONS:The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rt-PA within 4.5 hours after the onset of this disease. Therefore, intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.

OBJECTIVETo compare the expression differences of breast cancer resistance protein(BCRP/ABCG2) and P-glycoprotein(P-gp) in breast cancer tissue before chemotherapy and in residual breast cancer tissue, and to explore its correlation with breast cancer stem cells.

METHODSImmunohistochemistry was used to detect the expression of ABCG2, P-gp, and breast cancer stem cells(BCSCs) markers(CD44 and CD24) in breast cancer tissue before chemotherapy and residual breast cancer tissue after chemotherapy. Immunofluorescence was applied for determination of the CD44 and CD24 protein expressions of BCSCs microspheres cells. The monoclone-forming ability of BCSCs microspheres cells was detected by limited dilution assay. The expressions of ABCG2, P-gp, CD44, and CD24 proteins were detected by Western blot.

RESULTSCompared with those in breast cancer tissue before chemotherapy, the expression levels of ABCG2 and P-gp were positively correlated with the expression level of CD44 protein(Χ(2)=41.34, r=0.83;Χ(2)=22.81, r=0.61) in residual breast cancer tissue after chemotherapy;meanwhile, they were negatively correlated with the expression of CD24 protein(Χ(2)=-21.25, r=0.72;Χ(2)=-17.26, r=0.65) (all P<0.05) .The diameter of BCSCs microspheres were increased significantly after chemotherapy.The content of BCSCs increased by about 2.5 times after chemotherapy.The expressions of ABCG2, P-gp and CD44 proteins significantly increased and that of CD24 protein significantly declined(P<0.05) .

CONCLUSIONChemotherapy endows residual breast cancer tissue with cancer stem cells-like features, leading to multidrug resistance of breast cancer.

ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Breast Neoplasms ; drug therapy ; metabolism ; CD24 Antigen ; metabolism ; Cell Culture Techniques ; Drug Resistance, Neoplasm ; Female ; Humans ; Hyaluronan Receptors ; metabolism ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasm, Residual ; Neoplastic Stem Cells ; cytology ; metabolism