Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (G_s) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca²⁺]_i of GCs through the IP₃-sensitive pathway and was blocked in Ca²⁺-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct G_s/cAMP-PKA/IP₃/Ca²⁺/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.

OBJECTIVETo study the effect of aqueous extract of several kinds of herbs on human platelet aggregation and expression of P-selectin in vitro.

METHODSBlood was collected from volunteers. Effects of the prepared water extracts of herbs on platelet aggregation were monitored on a Packs-4 aggregometer. The fluorescence intensity of water extracts of Caulis Spatholobi, Flos Carthami and Rhizoma Curcumae on the expression of P-selectin in human platelets of healthy persons was measured with flow cytometry.

RESULTSOut of several herbs investigated, Flos Carthami and Rhizoma Curcumae potently inhibited platelet aggregation after incubation with platelet-rich plasma (PRP) for 15 min. Caulis Spatholobi Flos Carthami and Rhizoma Curcumae inhibited adenosine-5'-diphosphate (ADP) or platelet activating factor (PAF)-induced platelet aggregation in PRP in a dose-dependent manner. In contrast to Flos Carthami and Rhizoma Curcumae, Caulis Spatholobi could not inhibit thrombin-induced platelet aggregation. Despite its inability to inhibit thrombin-induced platelet aggregation in PRP, Caulis Spatholobi had a greater anti-aggregating activity in PRP induced by ADP or PAF. Caulis Spatholobi and Flos Carthami showed significant inhibitory effects on the expression of P-selectin.

CONCLUSIONSCaulis Spatholobi, Flos Carthami and Rhizoma Curcumae have potent anti-platelet properties, and their inhibitory actions are mediated via different mechanisms. Caulis Spatholobi inhibited ADP-induced platelet aggregation but not by thrombin, indicating that its mechanism of action might be independent of the thromboxane pathway. The effect of Caulis Spatholobi and Flos Carthami were associated with suppressing the expression of P-selectin.

Adult ; Blood Platelets ; drug effects ; metabolism ; Curcuma ; chemistry ; Fabaceae ; chemistry ; Humans ; P-Selectin ; metabolism ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Function Tests ; Water ; chemistry ; Young Adult

OBJECTIVETo investigate the effect of RNA interference (RNAi)-mediated silencing of the SREBP2 on inflammatory cytokine-induced cholesterol accumulation in HepG2 cells.

METHODSShort-hairpin (sh)RNA targeting SREBP2 or negative control (NC) shRNA were transfected into HepG2 cells by a liposomal method. G418-selective culturing was used to obtain the SREBP2 shRNA HepG2 and NC shRNA HepG2 cell lines. The two cell lines were cultured in serum-free medium and left untreated (control) or treated with TNF-a (20 ng/ml), low-density lipoprotein (LDL) loading (100 mug/ml), or a combination LDL plus TNF-a treatment. Lipid accumulation was evaluated by oil red O (ORO) staining. Intracellular cholesterol level was measured by enzymatic assay. The mRNA and protein levels of SREBP2 and its downstream target genes, LDL receptor (LDLr), and HMGCoA reductase, were measured by real-time PCR and Western blotting, respectively.

RESULTSSREBP2 shRNA HepG2 and NC shRNA HepG2 stable cell lines were successfully established. ORO staining and cholesterol quantitative analysis showed that LDL loading significantly increased intracellular cholesterol and that expression of SREBP2 further exacerbated the inflammatory cytokine-induced lipid accumulation, as seen in NC shRNA HepG2 cells. LDL loading of NC shRNA HepG2 decreased the gene and protein expressions of SREBP2, LDLr, and HMGCoA reductase, but the suppressive effect was overridden by inflammatory cytokine. SREBP2 shRNA HepG2 cells showed lower levels of cholesterol accumulation under LDL loading and inflammatory stress conditions. Moreover, the mRNA and protein levels of SREBP2, LDLr, and HMGCoA reductase were much lower than in NC shRNA HepG2 cells under the same conditions.

CONCLUSIONInflammatory cytokine exacerbated cholesterol accumulation in HepG2 via disrupting SREBP2. RNAi-mediated inhibition of SREBP2 expression significantly ameliorated the cholesterol accumulation induced by inflammatory cytokine.

Cholesterol ; metabolism ; Hep G2 Cells ; Humans ; Inflammation ; RNA Interference ; RNA, Small Interfering ; Sterol Regulatory Element Binding Protein 2 ; genetics ; Tumor Necrosis Factor-alpha ; pharmacology

Objective This study investigated the impact of metabolic syndrome on the development of cardio-cerebral vascular (CVD) events in a pre-hypertensive population.Methods The data used in this prospective study was derived from the Kailuan study cohort ( n =101 510).Prehypertension was diagnosed in 29 968 (mean age:50 ±9 years and 23 744 males) individuals by the JNC Ⅶ criteria and these subjects were further classified into metabolic syndrome positive ( MS +,n =3447) and MS negative ( MS -,n =26521 ) groups according to the modified 2004 Chinese Diabetes Society criteria.Subjects were followed up for 38- 53 (mean 47 ± 5 ) months and first-ever CVD events were recorded.Baseline anthropometric and laboratory features were obtained by physical examination from June 2006 to October 2007 and the last follow-up day was December 31,2010.Multivariable Cox proportional hazards regression models were used to analyze the risk factors of first-ever CVD events.Results There were 354 CVD events during follow up.The incidences of CVD events ( 1.80％ vs. 1.28％ ) and cerebral infarction ( 1.10％ vs.0.57％ ) were significantly higher in the MS + group than in the MS - group ( all P ＜ 0.05 ).After adjustment for other established CVD risk factors,the hazards ratio was 1.45 (95％CI:1.10 -1.92) for total CVD events and 1.84 ( 95％ CI:1.27 - 2.67 ) for cerebral infarction events in MS + group.Conclusions In this cohort,metabolic syndrome is linked with increased risk for CVD events.

Objective To compare the clinical features of severe hand foot and mouth disease between enterovirus(EV)71 and other EV to find specific diagnosis index of EV71 severe hand foot and mouth disease.Methods Case definition were adopted from national guideline of hand foot and mouth disease diagnose(Version 2010).Clinical data of severe hand foot and mouth disease came from case history and contents of questionnaire would include the ones between the time of onset and diagnoses being made.EV and EV71,Cox A16 nucleic acid tested were by RT-PCR in stopl samples.Clinical features of severe hand foot and mouth disease between EV71 and other EV were compare.Results There appeared statistical differences between neurologic symptoms such as tremor,myoclonic jerk,listlessness,convulsion and white blood cell counts in CSF(P<0.05).Results from the step Fisher discriminant analysis showed only tremor and white blood cell had an increase in CSF,with statistically significant differences.The discriminant equation of EV71 was Y=3.059X1+3.83X5-2.742 and the equation of other EV was Y=1.634X1+1.623X5-1.693.The specificity of EV71 was 91% and the specificity of other EV Was 40%.Conclusion The increase of clinical features of tremor and white blood cell in CSF could be used as diagnosis index of severe EV71.

OBJECTIVETo investigate the association between the morphological features of biopsy-diagnosed high grade intraepithelial neoplasia in the gastric mucosa and the postoperative pathology.

METHODSFifty-one patients with biopsy-diagnosed high grade intraepithelial neoplasia in the gastric mucosa were retrospectively analyzed. Thirty-three patients underwent surgery. The morphology of lesions under endoscopy and histopathological findings of the surgical specimens were investigated.

RESULTSOf the 51 patients, 43 had superficial lesions similar to early gastric cancer under endoscopy, 8 were similar to advanced carcinoma. In the 33 surgical cases, high grade intraepithelial neoplasia of gastric mucosa was confirmed on postoperative pathological examination in 13 (39.4%) patients, adenocarcinoma was identified in the remaining 20 patients (60.6%), including 14 early gastric cancers and 6 advanced carcinomas. Thirteen cases with high grade intraepithelial neoplasia confirmed postoperatively were superficial elevated or flat lesions less than 20 mm.

CONCLUSIONSPatients with biopsy-diagnosed high grade intraepithelial neoplasia in the gastric mucosa have a high risk of cancer. Thus aggressive follow-up and appropriate surgical interventions are recommended to avoid misdiagnosis.

Adult ; Aged ; Aged, 80 and over ; Biopsy ; Female ; Gastric Mucosa ; pathology ; Gastroscopy ; Humans ; Male ; Middle Aged ; Prostatic Intraepithelial Neoplasia ; pathology ; Stomach Neoplasms ; pathology

BACKGROUND AND OBJECTIVELittle is known about the incidence of hepatitis B virus (HBV) infection in Hodgkin's lymphoma patients. This study was to evaluate the impact of HBV infection on the survival of Hodgkin's lymphoma patient.

METHODSClinical data of 120 Hodgkin's lymphoma patients treated at the Sun Yat-sen University Cancer Center between January 2004 and October 2007 were collected. The impact of prognostic factors including HBV infection on survival was examined by univariate and multivariate analyses. A log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used for multivariate analysis.

RESULTSOf the 120 patients, 18 (15.0%) were hepatitis B virus surface antigen HBsAg-positive. The HBsAg-positive patients had lower 5-year survival rate than did the HBsAg-negative ones (66.9% vs. 91.3%, P = 0.006). When the patients were divided into early-stage (I + II) and advanced-stage (III + IV) groups, the 5-year survival rate was significantly different between the HBsAg-positive and -negative patients in early-stage group (64.8% vs. 96.0%, P < 0.001), while not significantly different in advanced-stage group (75.0% vs. 84.8%, P = 0.667). Both univariate and multivariate analyses showed that radiotherapy and HBV infection were independent prognosis factors for the patients with early-stage Hodgkin's lymphoma (P = 0.006 and 0.014, respectively).

CONCLUSIONSThe incidence of HBV infection is similar between Hodgkin's lymphoma patients and normal population. HBV infection is an independent prognosis factor for survival in the patients with early-stage Hodgkin's lymphoma.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Disease-Free Survival ; Female ; Hepatitis B ; blood ; Hepatitis B Surface Antigens ; blood ; Hodgkin Disease ; drug therapy ; radiotherapy ; virology ; Humans ; Male ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate

Background and Objective:Little is known about the incidence of hepatitis B virus(HBV)infection in Hodgkin's lymphoma patients.This study was to evaluate the impact of HBV infection on the survival of Hodgkin's lymphoma patient.Methods:Clinical data of 120 Hodgkin's lymphoma patients treated at the Sun Yat-sen University Cancer Center between January 2004 and October 2007 were collected.The impact of prognostic factors including HBV infection on survival was examined by univadate and multivariate analyses.A log-rank test was used for univadate analysis and the Cox proportional hazards regression model was used for multivadate analysis.Results:Of the 120 patients,18(15.0%)were hepatitis B virus surface antigen(HBsAg)-positive.The HBsAg-positive patients had lower 5-year survival rate than did the HBsAg-negative ones(66.9% vs.91.3%,P=0.006).When the patients were divided into early-stage(Ⅰ+Ⅱ)and advanced-stage(Ⅲ+Ⅳ)groups,the 5-year survival rate was significantly different between the HBsAg-positive and-negative patients in early-stage group(64.8% vs.96.0%,P＜0.001),while not significantly different in advanced-stage group(75.0% vs.64.8%,P=0.667).Both univariate and multivariate analyses showed that radiotherapy and HBV infection were independent prognosis factors for the patients with early-stage Hodgkin's lymphoma (P=0.006 and 0.014,respectively).Conclusions:The incidence of HBV infection is similar between Hodgkin's lymphoma patients and normal population.HBV infection is an independent prognosis factor for survival in the patients with early-stage Hodgkin's lymphoma.

INTRODUCTIONBased on the estimate results of the capacity and preparedness of Beijing hospitals to respond to pandemic influenza, using flu surge model to evaluate its applicable hypothesis and to provide government with sentient strategy in planning pandemic influenza. Through collection of medical resources information, we calculated the possible impaction on hospitals by Flu Surge model and explored the applicable hypothesis in model operation through a questionnaire, direct observation and group discussion in 3 hospitals in Beijing. Based on flu surge model estimation during a 6-week epidemic from a pandemic virus with 35% attack rate, Beijing would have had an estimation of 5 383 000 influenza illnesses, 2 691 500 influenza outpatients, 76 450 influenza hospitalizations and 14 508 excess deaths. For a 6-week period with 35% attack rate, there would be a peak demand for 8% of beds, 210% of ICU beds, and 128% of ventilators estimated. Outpatients in different level hospital were quite disproportionated with 1742/ hospital/day, 650/hospital/day, and 139/hospital/day respectively. The sampled health workers had a mastery of 63.4% of the total knowledge and skills of diagnosing and treating of influenza, 73.5% of them washed their hands and 63.5% used PPE correctly. The total beds capacity, medical beds capacity and respiratory medical beds capacity would increase 8%, 35% and 128% respectively.

CONCLUSIONThe estimation results could be referenced when planning the pandemic strategy, but the results should be treated objectively when considering the hypothesis and practical situation in this model being used.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Disease Outbreaks ; statistics & numerical data ; Female ; Hospital Bed Capacity ; Hospital Planning ; Hospitalization ; statistics & numerical data ; Humans ; Infant ; Infant, Newborn ; Influenza, Human ; epidemiology ; Male ; Middle Aged ; Models, Statistical ; Surge Capacity ; Young Adult

OBJECTIVETo investigate the mRNA expression of bFGF and MMP-9 in gastric carcinomas and to find their correlation with tumor microvascular density (MVD), invasion, metastasis and patients survival.

METHODSIn situ hybridization and immunohistochemistry technique were used to test the expression of bFGF mRNA and MMP-9 mRNA and protein of CD34 in 105 specimens of gastric carcinoma.

RESULTSIn situ hybridization revealed that the positive rates of bFGF mRNA and MMP-9 mRNA were 60.95 and 58.1%, respectively; The mean MVD (46.09 +/- 11.52, 43.75 +/- 13.41 piece/0.72 mm(2)) in tumors with bFGF mRNA and MMP-9 mRNA positive expression was significantly higher than that (29.41 +/- 12.47; 33.45 +/- 13.92 piece/0.72 mm(2)) in tumors with their negative expression, respectively; The positive expression rates of bFGF and MMP-9 mRNA were correlated to invasion depth (r(s) = 0.211, P = 0.031; r(s) = 0.335, P = 0.001, respectively), growing pattern (r(s) = 0.324, P = 0.001; r(s) = 0.267, P = 0.006, respectively), vessel invasion (r(s) = 0.579, P = 0.001; r(s) = 0.209, P = 0.032, respectively), lymph node metastasis (r(s) = 0.405, P = 0.001; r(s) = 0.343, P = 0.001, respectively) and distant metastasis (r(s) = 0.474, P = 0.001; r(s) = 0.468, P = 0.001, respectively), but not correlated to tumor type (r(s) = 0.134, P = 0.173; r(s) = 0.103, P = 0.145, respectively) and differentiation (r(s) = 0.096, P = 0.332; r(s) = 0.102, P = 0.298, respectively); And then, the mean MVD in tumors with infiltrating type, stage T(3)-T(4), vessel invasion, lymph node metastasis and distant metastasis was significantly higher than that in tumors with expanding type (t = 10.105, P = 0.001), stage T(1)-T(2) (t = 5.961, P = 0.001), non-vessel invasion (t = 7.394, P = 0.001), non-lymph node metastasis (t = 3.819, P = 0.01) and non-distant metastasis (r = 10.578, P = 0.001); There was a positive relationship between MVD and bFGF mRNA and MMP-9 mRNA (t = 3.207, P = 0.002; t = 7.035, P = 0.001), respectively; the mean survival time in cases with positive bFGF mRNA and MMP-9 mRNA and MVD value >/= 39.5 was significantly shorter than that in cases with their negative expression and MVD value < 39.5.

CONCLUSIONSbFGF and MMP-9 promote angiogenesis in gastric cancer. Test of the expression of bFGF and MMP-9 may act as an useful index to determine angiogenesis, invasion, metastasis and patients survival.

Adult ; Aged ; Biomarkers, Tumor ; biosynthesis ; genetics ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; genetics ; Humans ; In Situ Hybridization ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; RNA, Messenger ; biosynthesis ; Stomach Neoplasms ; metabolism ; mortality ; pathology ; Survival Rate