ObjectiveTo investigate the correlation of hippocampal synaptic plasticity with spatial learning and memory under normal and pathological condition,and provide experimental evidence for the coincidence of hippocampal late-phase long-term potentiation (L-LTP) and behavioral experiments.Methods 38 SD rats were randomly divided into two groups,control and AD model.First,Morris water maze was used to test the ability of spatial learning and memory of rats.The escape latencies for rats to search for an underwater platform in 5 days of navigation tests and the swimming time percentage in target qtuadrant on the 6th day after withdrawing the platform in probe trails were recorded.Then,in vivo hippocampus L-LTP of field excitatory postsynaptic potential (fEPSP)in CA1 region was recorded after delivering high frequency stimulation (HFS).ResultsBilateral intrahippocampal injection of 4 nmol amyloid β peptide ( Aβ 25-35 ) significantly impaired spatial learning and memory of rats in water maze tests,as well as in vivo hippocampal L-LTP.In control group,there was a significant negative correlation between the amplitude of fEPSP and the escape latency ( r =-0.8306,P ＜ 0.01 ) and a significant positive correlation between the amplitude of fEPSP and the swimming time percentage in target quadrant ( r=0.7709,P＜0.01 ).In AD model group,similar correlations were found,with a correlation coefficient of r =-0.7675 (P ＜0.01 ) and r =0.8049 (P ＜ 0.01 ),respectively.When putting all data from the two groups together,the hippocampal L-LTP was more correlated with escape latency ( r =-0.9124,P ＜ 0.01 ) and swimming time percentage ( r=0.9745,P＜0.01).ConclusionThere is very close correlation between the hippocampal L-LTP and the spatial learning and memory behavior in rats,suggesting that the hippocampal L-LTP may be involved in the electrophysiological mechanism of spatial learning and memory in rats,and the impairment of L-LTP could partly represent the deficits in cognitive function of animals.

OBJECTIVETo evaluate the correlation of liver hardness testing

RESULTSobtained by FibroTouch and FibroScan and the liver pathological stage.

METHODSSeventy-five patients with chronic hepatitis B who presented to our clinic between January 2011 and April 2013 were examined with FibroTouch and FibroScan to evaluate the degree of liver fibrosis. Forty-six of those patients also underwent liver biopsy examination.

THE RESULTSfrom technology-based testing and histopathological evaluation of the biopsy were compared by statistical analysis to determine the consistency of FibroTouch and FibroScan in regard to histological stage.

RESULTSAnalysis by paired t-test showed that the

RESULTSfrom FibroTouch and FibroScan were not significantly different (t = -0.17, P =0.8616), and the correlation coefficient from Pearson's correlation analysis was 0.9949 (P less than 0.05), suggesting that the two technologies'

RESULTSare correlated. Based on the histopathology

RESULTSfor liver fibrosis stage, the FibroTouch diagnosis of liver fibrosis more than or equal to S 1 had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.889, diagnosis of liver fibrosis more than or equal to S2 had a ROC AUC of 0.941, diagnosis of liver fibrosis more than or equal to S3 had a ROC AUC of 0.908, and diagnosis of liver fibrosis more than or equal to S4 had a ROC AUC of 0.911.

CONCLUSIONCompared to FibroScan, FibroTouch has a better ability for detecting liver fibrosis and a better consistency with liver pathological stage determined by histopathological analysis.

Adult ; Aged ; Area Under Curve ; Biopsy ; Case-Control Studies ; Elasticity Imaging Techniques ; instrumentation ; Female ; Hepatitis B, Chronic ; pathology ; Humans ; Liver ; pathology ; Male ; Middle Aged ; Prospective Studies ; Young Adult

Objective:The present study was aimed to evaluate the nutritional risk using nutritional risk screening 2002 (NRS2002) score and to investigate the impact of nutrition support on clinical outcome in hospitalized patients.Methods:Six hundred and ninety four hospitalized patients were recruited.NRS 2002 was applied to evaluate the nutritional risk of patients.Meanwhile,the effect of nutrition support on complication rate was evaluated between different types of patients.Results:14.0％ of patients had malnutrition and the incidence of nutritional risk was 27.5％.Patients with nutritional risk had a higher complication rate (P ＜0.01).Totally,22.0％ (153/694) patients received nutrition support,including 81.7％ patients with nutritional risk and 18.3％ patients without nutritional risk.Patients with nutritional risk benefited from nutrition support,as shown by lower complication rate and shorter length of hospital stay.In patients with nutritional risk,complication rate was lower in enteral fed patients compared to parenteral fed patients.Conclusion:With nutritional risk screening,patients' nutritional status can be evaluated and appropriate nutrition support can be performed.Compared to those without nutritional risk,patients with nutritional risk will benefit more from nutrition support,as indicated by lower complication rate and reduced length of hospital stay.

Objective: To explore the correlation of non-coding RNA and the tumor-associated antigen midkine (MK) in SKOV3cells and the clinical significance for diagnosis of ovarian cancer. Methods: The Agilent′s gene chips (miRNAs chip and lncRNAs chip) were used to analyze the differential expression of miRNAs and lncRNAs in both MK-overexpressing SKOV3-MK cells and the control SKOV3-Con cells to screen the potential biomarkers in ovarian cancer. The clinical significance of midkine in the serum and tissues samples was analyzed for the patients with ovarian cancer by quantitative PCR combined with clinical data. Results: Compared with control SKOV3-con cells, MK overexpression significantly promoted the expressions of 11 miRNAs and 7 lncRNAs in SKOV3 cells (P＜0.01, ratio＞3 fold), reduced the expressions of 8 miRNAs and 13 lncRNAs (P＜0.01, ratio＜0.3). Results of qPCR showed that the expression level of miR489 was significantly lower in ovarian cancer tissues than that of the contralateral normal ovarian tissues, while HOTAIR was significantly elevated (P＜0.05). The expression level of HOTAIR in the serum of ovarian cancer patients was significantly higher than that in healthy controls group with same age (0.036±0.024 vs 0.019±0.020, P=0.002). ROC curve analysis of HOTAIR showed that the specificity was 66.7%, the sensitivity was 75.6% and the AUC value was 0.749 as a marker for serum detection of ovarian cancer when the cutoff value was 0.017 6. Conclusion Long-chain non-coding RNA HOTAIR may be served as a potential biomarker in serum of ovarian cancer patients.

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.

Objective:To observe the synaptic plasticity and characteristics of transmembrane calcium flux in the hippocampus of 3xTg-AD mice.Methods:According to different genotypes, 6-month-old mice were divided into two groups: APP/PS1/tau triple transgenic AD (3xTg-AD) model mice and wild type (WT) mice, with 13 mice in each group.Six mice were randomly selected from each group to do in vivo electrophysiological recording.Field excitatory postsynaptic potential (fEPSP) was evoked by test stimulation, paired-pulse facilitation (PPF) was induced by two stimuli, and long-term potentiation (LTP) was induced by high frequency stimulation (HFS) in the hippocampal CA1 region of mice.The remaining seven mice in each group were used to detect the transmembrane calcium influx and efflux in the slices of hippocampal CA1 region by using non-invasive micro-test technology (NMT). In the electrophysiological and NMT experiments, one mouse fell off respectively.Finally, five mice were enrolled in the electrophysiological experiment and six in the NMT experiment.SPSS 18.0 was used for statistical analysis of all data, and two independent sample t-test was used for comparison between the two groups. Results:(1) In the in vivo electrophysiological experiments, the fEPSP slopes of 3xTg-AD mice and WT mice evoked by test stimulation were stable within 30 min, and the average fEPSP slopes were ((97.8±2.3)%) and ((92.6±12.6)%), respectively.There was no statistical difference of the average fEPSP slopes between the two groups ( t=0.91, P>0.05). After paired-pulse stimulation, the PPF values of 3xTg-AD mice and WT mice were (1.58±0.69) and (1.74±0.17) respectively, and there was no statistical difference between the two groups ( t=0.50, P>0.05). At 30 min and 60 min post-HFS, the LTP values in 3xTg-AD mice were ((104.9±10.9)%) and ((98.0±10.8)%) respectively, which were significantly lower than those in WT mice((156.5±21.3)%, t=4.43, P<0.01; (162.5 ±19.7)%, t=5.92, P<0.01). (2) In NMT experiments, the standardized mean and peak velocities of glutamate-induced Ca 2+ influx in hippocampal CA1 region of 3xTg-AD mice were ((-2 166.0±425.0)%) and ((-3 539.6±1 270.9)%) respectively, which were significantly higher than those in WT mice((-735.3±262.9)%, t=6.81, P<0.01; (-917.3±271.7)%, t=4.89, P<0.01). The standardized average and peak velocities of low Ca 2+ solution-induced Ca 2+ efflux in 3xTg-AD mice were ((1 451.6±297.1)%) and ((1 968.7±227.3)%) respectively, which were significantly lower than those in WT mice((2 579.3±810.9)%, t=2.92, P<0.05; (3 420.4±954.8)%, t=3.31, P<0.01). Conclusion:The hippocampal synaptic plasticity impairment observed in 6-month-old 3xTg-AD may be closely related with the intracellular Ca 2+ overload caused by increased calcium influx and decreased calcium efflux.