Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Derris eriocarpa, a traditional Chinese medicine belonging to the family of Leguminosae, is widely distributed mainly over Yunnan, Guangxi and Guizhou of China. Modern pharmacological researches on this herb showed that it had extensive bioactivities, such as promoting urination, removing dampness and cough and reducing inspissated mucus and other biological activities. The extensive studies on the chemical constituents of this plant have resulted in the isolation of triterpenoids, steroids, fatty acid and others, but the flavone compounds haven't reported before. In our further research on the ethyl acetate of this plant, nine flavone compounds were obtained by column chromatography on silica gel, Sephadex LH-20, semi-prep HPLC, polyamide column chromatography and recrystallization for separation and purification. The structures were determined on the basis of extensive spectroscopic analysis, including MS, NMR experiments and comparison with spectroscopic data in the literature, respectively, as diosmetin (1), 3, 3'-di-O-methylquercetin (2), afromosin (3), 6, 3'-dihydroxy-7, 4'-dimethoxyisoflavone (4), odoratin (5), 7, 3'-dihydroxy-8, 4'-dimethoxyisoflavone (6), 6, 4'-dihydroxy-7, 3'-dimethoxyisoflavone (7), 5, 7, 4'-trihydroxy-3, 3', 5'-trimethoxyflavone (8), and alpinumisoflavone (9). All these compounds were isolated from Derris eriocarpa How for the first time. And the in vitro assays showed that compound 2 possessed moderate inhibitory activity against human cancer cells K562 and HEL.
Derris ; chemistry ; Flavonoids ; chemistry ; isolation & purification ; pharmacology ; Humans ; K562 Cells

Objective To explore the possible mechanisms of Galectin - 1(Gal - 1)protein in promoting the invasion and migration of gastric cancer cells. Methods After treated with different concentrations(0,1,5 μg/ mL)of Gal - 1 protein, the Trans - well model was used to analyze the invasion and migration ability of gastric cancer. WB and gelatin zymography method were used to detect the MMP - 9 expression and active form change in gastric cancer cells after Gal - 1 stimulate, in order to explore the possible molecular mechanisms of Gal - 1 protein in promoting the invasion and migration of gastric cancer cells. Results In cell migration assay,the number of gastric cancer cells BGC - 823 treated with 1and 5 μg/ mL Gal - 1 stimulate were 117 ± 8. 19 and 167 ± 7. 55,higher than that treated with 0 μg/ mL(P < 0. 05). The number of gastric cancer cells 7 901 treated with 1and 5 μg/ mL Gal - 1 stimulate were 151 ± 5. 13 and 190. 3 ± 6. 8,higher than that treated with 0 μg/ mL(P < 0. 05). In cell invasion assay,the number of gastric cancer cells BGC - 823 treated with 1and 5μg/ mL Gal - 1 stimulate were 51 ± 3. 6 and 76. 7 ± 9. 07,higher than that treated with 0 μg/ mL(P < 0. 05). The number of gastric cancer cells 7 901 treated with 1and 5 μg/ mL Gal - 1 stimulate were 74. 0 ± 7. 21 and 105. 3 ± 11. 37,higher than that treated with 0 μg/ mL(P < 0. 05). The migration and invasion level were significantly increased in gastric cancer cells after Gal - 1 stimulate. The MMP - 9 expression level and active form change in gastric cancer cells were also increased after Gal - 1 stimulate. Conclusion Gal - 1cound significantly promote gastric cancer cell migration and invasion by up - regulated the MMP - 9 expression and active its enzyme activity.

OBJECTIVE: To explore the distribution of inflammatory cells and positive expression of P-se- lectin glycoprotein ligand-1 (PSGL-1) in infant brainstem tissue from hand-foot-mouth disease related fatal brainstem encephalitis. METHODS: Twenty brainstem samples from infants suffered from brainstem en- cephalitis were collected as the experimental group. Ten brainstem samples from infants died of non- brain diseases and injuries were collected as the control group. The distribution of inflammatory cells and the expression of PSGL-1 in the two groups were examined by immunohistochemical method. The characteristics of the positive cells were observed. RESULTS: In brainstem tissue of the experimental group, there were sleeve infiltrations of inflammatory cells around the vessels and in the glial nodule. Microglia was the most and following was neutrophils around the vessels and in the glial nodule. There was a significant statistical difference among microglias, neutrophils and lymphocytes (P < 0.05). There was no sleeve infiltration in the control group. PSGL-1 protein was expressed widely in inflammatory cells in the experimental group, especially in the inflammatory cells around the vessels and in the glial nodule. But PSGL-1 positive staining could be observed significantly less in the control group comparing with the experimental group (P < 0.05). CONCLUSION Microglia is the main type of inflammatory cells involved in the progress of the fatal disease. Moreover, PSGL-1 could participate in the pathogenesis of hand-foot-mouth disease related fatal brainstem encephalitis.
Brain Stem/pathology* ; Encephalitis/pathology* ; Hand, Foot and Mouth Disease/pathology* ; Humans ; Infant ; Membrane Glycoproteins/metabolism* ; Microglia/pathology* ; Neutrophils/pathology*

OBJECTIVETo evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction (AMI).

METHODSTwenty-two male Chinese mini swines were randomized into 3 groups: sham-operation group (n=6), control group (n=8), and garlicin group (n=8). The distal part of left anterior descending coronary artery (LAD) in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography (CAG) and electrocardiograph (ECG), which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography (MCE) and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area (NRA) and risk area (RA).

RESULTSLeft ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group P<0.05) and 2 h after AMI (P<0.05). MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group (P <0.05). In double staining, NRA/RA in the garlicin group was 18.78%, significantly lower than that of the control group (49.84%, P<0.01).

CONCLUSIONSGarlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

Allyl Compounds ; pharmacology ; therapeutic use ; Animals ; Cardiotonic Agents ; pharmacology ; therapeutic use ; Contrast Media ; Disease Models, Animal ; Disulfides ; pharmacology ; therapeutic use ; Hemodynamics ; drug effects ; Male ; Myocardial Infarction ; complications ; diagnostic imaging ; drug therapy ; pathology ; Myocardial Reperfusion ; No-Reflow Phenomenon ; complications ; diagnostic imaging ; drug therapy ; pathology ; Swine ; Swine, Miniature ; Thiazoles ; metabolism ; Ultrasonography

BACKGROUNDAndrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers. The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.

METHODSCell proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay, and morphologic structure with transmission electron microscopy. Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2, Bax, and caspase-3 expressions.

RESULTSAndrographolide showed a time- and concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to controls, the number of cells in the G0-G1-phase increased significantly, S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and both early and late apoptotic rates increased significantly compared to the controls, all in a concentration-dependent manner. Bax and caspase-3 expressions were markedly increased, and Bcl-2 expression was decreased.

CONCLUSIONSAndrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression. Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.

Apoptosis ; drug effects ; Caspase 3 ; analysis ; genetics ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Stomach Neoplasms ; drug therapy ; pathology ; bcl-2-Associated X Protein ; analysis ; genetics

The paper is to report the development of a method of quantitative analysis of multi-components by high performance liquid chromatography (HPLC) for simultaneously determining paeoniflorin sulfonate (PS), paeoniflorin (PF) and albiflorin (AF) in sulfated Paeoniae Radix Alba. Moreover, the cytotoxicity of paeoniflorin sulfonate by MTT-assay and the acute toxicity of mice by administration of paeoniflorin sulfonate were evaluated. Chromatographic separation of paeoniflorin sulfonate, PF and AF were performed on a SHISEIDO CAPCELL PAK C18 column (250 mm x 4.6 mm, 5 microm) for HPLC and a mixture of acetonitrile and 0.02% phosphoric acid solution (15 : 85) as the mobile phase. As detector a spectrophotometer set at 230 nm; column temperature 30 degrees C; flow rate 1.0 mL x min(-1). The toxicity of paeoniflorin sulfonate was evaluated by in vitro cytotoxicity carried out on mouse and human primary hepatocytes, and by acute oral toxicity test carried out on mice. The calibration curve of paeoniflorin sulfonate, PF and AF revealed linearity in the range of 0.041 8 - 1.045 0, 0.023 5 - 0.587 5, and 0.039 8 - 0.995 0 mg x mL(-1), respectively (r > 0.999 8). The average recovery was ranged from 99.11% to 101.71%, RSD < 2%. Paeoniflorin sulfonate does not have any cytotoxicity to cells at all the tested concentrations (< or = 300 micromol x L(-1)) in the in vitro cytotoxicity assay. The maximum tolerance dose of paeoniflorin sulfonate solution and extraction of Paeoniae Radix Alba to mouse is 5 g x kg(-1) and 80 g x kg(-1) respectively. The contents of these three components in the samples were determined with the developed method. It is a rapid, convenient and accurate method to determine multi-components. The content of PF in sulfated Paeoniae Radix Alba is significantly lower, and there is negative correlationship between the content of paeoniflorin sulfonate and PF. The in vitro cytotoxicity assay and in vivo mouse acute toxicity test showed that there is no obvious toxicity of paeoniflorin sulfonate and water-soluble extract of sulfated Paeoniae Radix Alba.
Animals ; Benzoates ; analysis ; isolation & purification ; toxicity ; Bridged-Ring Compounds ; analysis ; isolation & purification ; toxicity ; Chromatography, High Pressure Liquid ; Glucosides ; analysis ; isolation & purification ; toxicity ; Hepatocytes ; drug effects ; Humans ; Mice ; Mice, Inbred ICR ; Monoterpenes ; Paeonia ; chemistry ; drug effects ; Plant Roots ; chemistry ; drug effects ; Plants, Medicinal ; chemistry ; drug effects ; Sulfur ; pharmacology ; Volatilization

BACKGROUNDAssessment of lymph node metastasis (LNM) is important in early gastric cancer (EGC) and affects treatment decisions. However, the relationship between clinicopathological characteristics and LNM in EGC remains unclear. This study therefore explored favorable predictors of LNM in EGC.

METHODSA total of 716 specimens from gastric cancer patients who underwent curative gastrectomy between 1996 and 2003 at Zhejiang Provincial People's Hospital were reviewed. Forty-five cases were EGC, and clinicopathological characteristics such as gender, age, tumor size, location, gross type, differentiation, invasion depth, and vessel involvement were assessed to identify predictive factors for LNM and survival time.

RESULTSThe overall cumulative 5-year survival rate of EGC patients was 88.92%. Among these, 22.4% developed LNM, which was associated with a poor 5-year survival rate of only 72.7%. Patients with tumors larger than 2 cm in diameters, with depth of tumor invasion to the submucosa, and with positive lymphatic or nerve involvement were also inclined to have poorer survival performances. EGC limited to the mucosa but poorly differentiated also had a high risk for LNM. Multivariate analysis identified lymphatic invasion and tumor size as independent prognosis factors related to survival in EGC patients.

CONCLUSIONSCareful planning is required in EGC patients at high risk of lymph node metastases. Endoscopic mucosal resection or endoscopic submucosal dissection and laparoscopic partial gastrectomy should be cautiously used in EGC, and curative gastrectomy including lymphatic dissection and postoperative adjuvant therapy might be considered to improve the prognosis.

Adult ; Aged ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Stomach Neoplasms ; mortality ; surgery ; Treatment Outcome

BACKGROUNDGastric cancer (GC) is the second leading cause of cancer mortality worldwide, and surgical resection is currently the only possible curative approach. Duodenal stump leakage is the most serious complication after radical gastrectomy, and optimal treatment is still lacking.

METHODSWe retrospectively reviewed 2034 cases of total or subtotal gastrectomy for GC from January 1995 to December 2009, including 465 cases of duodenal stump closure using purse-string suture (group A), 835 cases of duodenal stump treated with linear cutting stapler and seromuscular layer suture (group B), and 734 cases of duodenal stump closure using full-thickness and seromuscular layer suture (group C). We evaluated the surgical cost, operative time for duodenal stump closure, short-term postoperative complications, perioperative blood loss, and postoperative recovery.

RESULTSThere was no perioperative mortality in any group. Ninety-four postoperative (within 1 month) complications occurred: 18 abdominal bleeding, 14 anastomotic leakage, 15 abdominal infection, 36 wound infection, and 11 duodenal stump leakage. There was no significant difference among the groups in intra-abdominal hemorrhage, anastomotic leakage, abdominal infection and wound infection. No postoperative duodenal stump leakage occurred in group A, which had a significant difference compared with groups B and C (6 cases in group B and 5 cases in group C suffered duodenal stump leakage. P < 0.01). The surgical cost in groups A and C was significantly lower than in group B (P < 0.01), with no significant difference between groups A and C. The processing time for duodenal stump closure in groups A and B was significantly shorter than in group C (P < 0.01), with no significant difference between groups A and B. There was no significant difference in blood loss and postoperative recovery among the groups.

CONCLUSIONSDuodenal stump closure using purse-string suture seems to be a promising approach with shorter operative time, and lower cost and incidence of duodenal stump leakage in radical gastrectomy.

Aged ; Female ; Gastrectomy ; adverse effects ; methods ; Gastric Stump ; surgery ; Humans ; Male ; Middle Aged ; Postoperative Complications ; surgery ; Retrospective Studies ; Sutures

Objective To investigate the efficacy, safety and tolerance of bosentan, a dual endothelin receptor antagonist, in Chinese patients with idiopathic pulmonary arterial hypertension (IPAH).Methods Totally 79 IPAH patients (hemodynamic criteria confirmed by right heart catheterization) were included in this open-label, prospective multicenter study. Patients received 62. 5 mg of bosentan twice daily for the first 4 weeks, and then up-titrated to 125 mg twice daily for another 12 weeks. The primary end point was the change in exercise capacity showed by six-minute walk distance (6MWD) from baseline to 16 weeks. Secondary end points included the change in World Health Organization (WHO) functional class,Borg dyspnoea scale and systolic pulmonary artery pressure measured by echocardiography. Results The 6MWD increased from (343. 7 ± 93.7) meters at baseline to (397.5 ± 104. 4) meters after 16 weeks ( P ＜0. 01 ), WHO functional class and Borg dyspnoea scale were also significantly improved after 16 weeks therapy compared to baseline levels (all P ＜0. 01 ). Furthermore, the systolic pulmonary artery pressure was significantly decreased from (97.8±25.2) mm Hg (1 mm Hg=0. 133 kPa) to (92.8 ±29.5) mm Hg (P ＜0. 05) after 16 weeks bosentan treatment. There was no patient withdrawal from this study for safety consideration. Conclusion Bosentan therapy is well tolerated and can improve the exercise capacity and WHO functional class in Chinese IPAH patients.