ObjectiveTo explore whether fluoroethylnormemantine （FENM）， an NMDA receptor antagonist， could improve compulsive-like behaviors and to investigate its underlying mechanisms in the RU24969-induced obsessive-compulsive disorder （OCD） mouse model. MethodsThirty-two mice were randomly assigned to four groups： Saline （n=8）， RU24969 （n=8）， RU+FENM （n=8）， and FENM （n=8）. Mice received FENM or an equivalent volume of saline for pre-treatment， followed by RU24969 or saline for model induction 30 minutes later. Behavioral tests were performed 1 hour after modeling， and serum samples were collected to measure the level of brain-derived neurotrophic factor （BDNF）. Evans Blue dye was intravenously injected to assess dye content in brain tissue， thereby evaluating potential blood-brain barrier damage. ResultsFENM treatment significantly improved repetitive stereotyped circling behavior （F=39.850， P＜0.001） and alleviated persistent motor activity （F=50.200， P＜0.001） in RU24969 model mice. Additionally， FENM treatment significantly increased serum BDNF level in RU24969-induced OCD mice （F=18.930， P＜0.001）. ConclusionsFENM ， an NMDA receptor antagonist， may alleviate compulsive behaviors in OCD mice by modulating BDNF levels ， thereby exerting anti-compulsive effects. Neither the RU24969 model nor FENM treatment significantly affectes blood-brain barrier integrity.

Oral squamous cell carcinoma (OSCC) is mostly diagnosed at an advanced stage, with local and/or distal metastasis. Thus, locoregional and/or local control of the primary tumor is crucial for a better prognosis in patients with OSCC. Platelets have long been considered major players in cancer metastasis. Traditional antiplatelet agents, such as aspirin, are thought to be potential chemotherapeutics, but they need to be used with caution because of the increased bleeding risk. Podoplanin (PDPN)-expressing cancer cells can activate platelets and promote OSCC metastasis. However, the reciprocal effect of platelets on PDPN expression in OSCC has not been investigated. In this study, we found that direct contact with platelets upregulated PDPN and integrin β1 at the protein level and promoted invasiveness of human OSCC Ca9.22 cells that express low levels of PDPN. In another human OSCC HSC3 cell line that express PDPN at an abundant level, silencing of the PDPN gene reduced cell invasiveness. Analysis of the public database further supported the co-expression of PDPN and integrin β1 and their increased expression in metastatic tissues compared to normal and tumor tissues of the oral cavity. Taken together, these data suggest that PDPN is a potential target to regulate platelet-tumor interaction and metastasis for OSCC treatment, which can overcome the limitations of traditional antiplatelet drugs.

Objective: To investigate the effect of early multi-dimensional cardiac rehabilitation (CR) nursing mode on patients after percutaneous coronary intervention (PCI). Methods: From August 2017 to July 2018, 100 patients with coronary heart disease (CHD) underwent PCI in the Department of Cardiology, the Third Affiliated Hospital of Sun Yat-sen University were selected as subjects. According to the random number table, the patients were divided into control group and observation group, 50 in each group. The control group received routine CR nursing intervention, and the observation group was given early multi-dimensional CR nursing mode for intervention. All patients were followed up for 6 months. The incidence of major cardiovascular adverse events (MACE) was observed 1 month and 6 months of follow-up. Patients with somatization were evaluated on the 2nd day after PCI and in the first month of follow-up using the Somatic Self-rating Scale (SSS). In the first month and the 6th month of follow-up, patient compliance was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8). Results: During the study period, 3 patients were detached from each group, and there were 47 patients in both groups who completed the study. The incidence of MACE in the control group in 1 month and 6 months was 8.51% (4/47) and 4.26% (2/47), respectively. The incidence of MACE in the observation group was 10.64% (5/47) and 4.26%, (2/47) respectively. There was no significant difference in the incidence of MACE between the two groups (χ² value was 0.123, 0.000, P>0.05). In the first month of follow-up, the SSS scores of the control group (34.32±6.59) and the observation group (31.04±7.04) were lower than those of the second day after surgery (37.21±6.19, 37.43±7.29), and the difference was statistically significant (t value was 4.633, 2.660, P<0.05). The SSS scores of the observation group were lower than those of the control group, and the difference was statistically significant (t value was 2.330, P<0.05). In the first month of follow-up, there was no significant difference in MMAS-8 score between the two groups (P>0.05). In the 6th month of follow-up, the MMAS-8 score (5.72±0.62) in the control group was lower than the first month of follow-up (6.93±0.54), and the difference was statistically significant (t value was 10.028, P<0.05). The MMAS-8 score of the control group was lower than that of the observation group (6.89±0.58), and the difference was statistically significant (t value was 9.490, P<0.05). There was no significant difference in MMAS-8 score between the observation group in the first month of follow-up and the sixth month of follow-up (P>0.05). Conclusion Early multi-dimensional CR nursing mode has a limited effect on improving the incidence of MACE in patients after PCI, but it can effectively reduce the somatization symptoms of patients and maintain good medication compliance.

Objective: To investigate the association between gene polymorphism of vesicular monoamine transporter type 2(VMAT2) and schizophrenia in Han Chinese population. Methods: 430 patients with schizophrenia and 470 age-sex matched controls were recruited from four mental health centers. All patients were diagnosed by two psychiatrists based on the Structured Clinical Interview for DSM Disorders (SCID). The ligase detection reactions (LDR) method was used to assess the polymorphism of the two SNPs (rs363371 and rs363324) of VMAT2. Results: No associations of two SNPs with schizophrenia was found. When we stratified males and females for the analysis, we found that that in the recessive model of rs363371, there was an obvious significant association between rs363371 and schizophrenia in males (OR=0.564, 95% CI=0.357–0.892, p=0.014) but not females. For the association between rs363324 and schizophrenia, no association was found in either males or females. No association was found when stratifying early-onset schizophrenia and late-onset schizophrenia. Conclusion Our findings indicate that both rs363371 and rs363324 were not associated with schizophrenia, while it seemed that the AA genotype of rs363371 plays a protective effect in male Chinese in developing schizophrenia.

PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. MATERIALS AND METHODS: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.
Biomarkers ; Capecitabine ; Chemotherapy, Adjuvant ; Disease-Free Survival ; DNA Repair ; Humans ; Immunohistochemistry ; Prognosis ; Prospective Studies ; Recurrence ; Stomach Neoplasms ; Thymidylate Synthase

Objective To investigate the role of dexmedetomidine (DEX) in lipopolysaccharide (LPS)-induced release of cell cytokines from monocyte macrophage RAW264.7 and nuclear transcription factor (NF)-κB signal pathway. Methods RAW264.7 cell lines were seeded in 6-well plates with a density of 1×106/mL (2 mL/hole) and randomly divided into control group (PBS), DEX group (10 ng/mL), LPS group (1 μg/mL) and LPS (1 μg/mL)+DEX (10 ng/mL) group. After incubation of 3, 6, 12 and 24 h, ELISA was employed to detect the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1βand high mobility group box (HMGB)-1 in the supernatants of 6 wells in each group. Then, 6 wells in each group were chosen at incubation of 12 h for determination of NF-κB signal pathway related proteins phosphorylated (p)-P65 and p-P50 expressions by Western blotting. Results As compared with those in the control group, the concentrations of TNF-α, IL-1β and HMGB-1 in the supernatant of LPS group were significantly increased (P<0.05), and the expressions of p-P65 and p-P50 were significantly increased in the LPS group (P<0.05). As compared with those in the LPS group, the levels of TNF-α, IL-1β and HMGB-1 were statistically decreased, and the expressions of P65 and P50 were significantly down-regulated in the DEX group (P<0.05). Conclusion DEX could inhibit the release of cells cytokines from RAW264.7 and decrease the levels of NF-κB signal pathway related protein expressions.

After communication with professional course teachers, clinical experts and graduates by investigation, informal discussion and expert interviews, the course and teaching of rehabilitation therapy was reformed to make the students not only meet the skill requirement,but also acquire basic theory and sustainable develop in their career.

OBJECTIVE: To establish an in vitro method to culture mesenchymal stem cells(MSCs) derived from human nasal mucosa, and explore their stemness and differentiation potential. METHOD: Based on the observation of distribution of MSCs in human nasal mucosa, we cultured and proliferated MSCs in vitro and identified the expression of stem cell markers on them including Nestin, CD133, Vimentin and Sa114 with immunofluorescence. The MSCs were induced to differentiate to osteoblasts with medium containing dexamethasone, ascorbic acid and beta sodium glycerophosphate, and to neurons with Neurobasal medium containing B27, ATRA and TSA. Histochemistry and immunofluorescence were applied to evaluate the differentiation. RESULT: The nestin and vimentin immunofluorescence-positive MSCs existed extensively in human nasal mucosa. While the MSCs were cultured in the osteogenic-inducing medium, activities of alkaline phosphatase were increased significantly, and bone nodules were found on the surface of the osteoblasts by alizarin red staining. After the induction by neural-inducing medium, the MSCs adopted neuron like appearance with many slim protrusions interconnected as a network. The induced cells expressed neural markers NF-200 and BM88 strongly. CONCLUSION The MSCs derived from human nasal mucosa are multipotent stem cells and can be utilized as seed cells to repair bone or neural injury.
Alkaline Phosphatase ; metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Humans ; Mesenchymal Stem Cells ; cytology ; metabolism ; Multipotent Stem Cells ; Nasal Mucosa ; cytology ; Neurons ; Osteoblasts ; cytology

Objective To investigate the effects of the fibrin scaffold on the differentiation and the proliferation of neural stem cells and astrocytes. Methods Neural stem cells and the gliocytes derived from spinal cord were cultured in vitro respectively. The purified neural stem cells or gliocytes were seeded separately onto the fibrin scaffolds as experimental group and the glass slides modified with poly-L-lysine(PLL)as control group. At different time in culture the neural stem cells were immunofluorescence stained with antibodies against the marker of neurons I.e. Neurofilament(NF).The length of NF-positive neuritis was masured and the average value was calculated in the culture well (n=4). The gliocytes were immunofluorescence stained with antibodies against the marker of astrocytes I.e. Glial fibrillary acidic protein (GFAP ). The total number of the cells and the GFAP-positive cells were counted from 5 different fields of vision in the culture well (n=4), then the average ratio of GFAP-positive cells was calculated. The differentiation of neural stem cells, the extension of neurites and the proliferation of astrocytes on the fibrin scaffolds were compared with those on the slides. The protein of GFAP was detected by Western blotting to analyse the mature degree of astrocytes. All above experiments were repeated 3 times respectively. Results Immunofluorescence staining showed that the NF-positive neurites in the fibrin scaffold group were longer than those in the control group, whereas GFAP-positive cells were fewer than those in the control group. The expression of GFAP in the cells on the scaffold was lower than that in the control group.Conclusion The fibrin scaffold could promote differentiation of the neural stem cells to neurons and extension of the neurites. Meanwhile, the scaffold could inhibit proliferation and mature of the astrocytes.

Chronic and heavy alcohol consumption is one of the causes of heart diseases. However, the effects of ethanol on insulin sensitivity in myocardium has been unclear. To investigate the effects of ethanol on the expression of AMP-activated protein kinase (AMPK), myocyte enhancer factor 2 (MEF2) and glucose transporter 4 (GLUT4), all of which are involved in the regulation of insulin sensitivity, in the myocardium, we performed three parts of experiments in vivo and in vitro. I: Rats were injected with 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR, 0.8 mg.kg(-1)) for 2 h. II: Rats received different dose (0.5, 2.5 or 5 g.kg(-1).d(-1)) of ethanol for 22-week. III: Primary neonatal rat cardiomyocytes were isolated and treated with or without 100 mM ethanol or 1 mM AICAR for 4 h. The cardiac protein and mRNA expression of AMPKalpha subunits, MEF2 and GLUT4 were observed by western-blotting and RT-PCR, respectively. Serum TNFalpha levels were assessed by ELISA. The results showed chronic ethanol exposure induced insulin resistance. Ethanol decreased the mRNA levels of AMPKalpha1 and alpha2, the protein levels of total- and phospho-AMPKalpha in cardiomyocytes. Similarly, ethanol showed inhibitory effects on both the mRNA and protein levels of MEF2A and 2D, and GLUT4 in a dose-response-like fashion. Correlation analysis implied an association between phospho-AMPKalpha and MEF2A or MEF2D, and between the levels of MEF2 protein and GLUT4 transcription. In addition, ethanol elevated serum TNFalpha level. Taken together, chronic ethanol exposure decreases the expression of AMPKalpha and MEF2, and is associated with GLUT4 decline in rat myocardium.
AMP-Activated Protein Kinases/genetics/*metabolism ; Aminoimidazole Carboxamide/analogs & derivatives/pharmacology ; Animals ; Enzyme Activation/drug effects ; Ethanol/*administration & dosage/*pharmacology ; Feeding Behavior/*drug effects ; Gene Expression Regulation/drug effects ; Glucose Transporter Type 4/genetics/*metabolism ; Insulin/pharmacology ; Insulin Resistance ; Male ; Myocardium/*enzymology ; Myogenic Regulatory Factors/antagonists & inhibitors/genetics/*metabolism ; Protein Isoforms/antagonists & inhibitors/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Rats ; Rats, Wistar ; Ribonucleotides/pharmacology ; Time Factors ; Tumor Necrosis Factor-alpha/blood