AIM:To investigate the role of extracellular signal-regulated kinase 5(ERK5) in platelet aggrega-tion in vitro and arterial thrombosis in vivo. METHODS:The expression and phosphorylation levels of ERK5 in human platelet were detected by Western blot. The effects of ERK5 selective inhibitor XMD8-92 on platelet aggregation and dense granule secretion were detected by Chrono-Log aggregometer. The effect of ERK5 on in vivo thrombosis was analyzed using an FeCl3artery thrombosis model. The effects of XMD8-92 on protein kinase B (PKB/Akt) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) phosphorylation levels were determined by Western blot. RESULTS:ERK5 was stably expressed in human platelets and its phosphorylation level increased significantly after platelet activation (P<0.05). XMD8-92,a selective inhibitor of ERK5,inhibited platelet aggregation and dense granule secretion in response to several platelet stimulators (P<0.05). The results of Western blot showed that XMD8-92 inhibited Akt phosphorylation level by down-regulating PTEN Ser370 phosphorylation and enhancing PTEN activity. The pathway was further confirmed u-sing platelet specific PTEN deficiency mice. The first occlusion time was obviously extended in the mice intravenously given XMD8-92 in the FeCl3-induced carotid artery injury model. CONCLUSION:ERK5 plays a role in platelet activation and arterial thrombosis by influencing PTEN and Akt phosphorylation.

OBJECTIVETo compare the efficacy difference in the treatment of shoulder pain in post-stroke shoulder-hand syndrome among floating acupuncture, oral administration of western medicine and local fumigation of Chinese herbs.

METHODSNinety cases of post-stroke shoulder-hand syndrome (stage I) were randomized into a floating acupuncture group, a western medicine group and a local Chinese herbs fumigation group, 30 cases in each one. In the floating acupuncture group, two obvious tender points were detected on the shoulder and the site 80-100 mm inferior to each tender point was taken as the inserting point and stimulated with floating needling technique. In the western medicine group, mobic 7.5 mg was prescribed for oral administration. In the local Chinese herbs fumigation group, the formula for activating blood circulation and relaxing tendon was used for local fumigation. All the patients in three groups received rehabilitation training. The floating acupuncture, oral administration of western medicine, local Chinese herbs fumigation and rehabilitation training were given once a day respectively in corresponding group and the cases were observed for 1 month. The visual analogue scale (VAS) and Takagishi shoulder joint function assessment were adopted to evaluate the dynamic change of the patients with shoulder pain before and after treatment in three groups. The modified Barthel index was used to evaluate the dynamic change of daily life activity of the patients in three groups.

RESULTSWith floating acupuncture, shoulder pain was relieved and the daily life activity was improved in the patients with post-stroke shoulder-hand syndrome, which was superior to the oral administration of western medicine and local Chinese herbs fumigation (P < 0.01). With local Chinese herbs fumigation, the improvement of shoulder pain was superior to the oral administration of western medicine. The difference in the improvement of daily life activity was not significant statistically between the local Chinese herbs fumigation and oral administration of western medicine, the efficacy was similar between these two therapies (P > 0.05).

CONCLUSIONThe floating acupuncture relieves shoulder pain of the patients with post-stroke shoulder-hand syndrome promptly and effectively, and the effects on shoulder pain and the improvements of daily life activity are superior to that of the oral administration of western medicine and local Chinese herbs fumigation.

Acupuncture Therapy ; Aged ; Female ; Humans ; Male ; Middle Aged ; Reflex Sympathetic Dystrophy ; etiology ; rehabilitation ; therapy ; Shoulder Pain ; etiology ; rehabilitation ; therapy ; Stroke ; complications ; Treatment Outcome

OBJECTIVETo investigate the relationship between polymorphism of Ghrelin gene and serum levels of lipoprotein in Han Chinese with or without coronary heart disease (CHD) risk factors.

METHODSPCR restriction fragment length polymorphism assay was used to detect the distribution of genotypes of Ghrelin gene in 225 Han Chinese (40 to 69 years-old) with CHD risk factors, 78 subjects without CHD risk factors served as normal controls. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein (VLDL) were measured to analyze the relationship with the polymorphism of Ghrelin gene.

RESULTSGhrelin genotype frequencies of AA, AG, GG (0.975, 0.025, 0.00 in control group and 0.956, 0.040, 0.004 in the high-risk group, all P > 0.05) as well as the allele frequencies of A, G (0.987, 0.013 in control group and 0.976, 0.024 in the high-risk group, all P > 0.05) were similar between the groups. HDL-C levels of the Arg/Gln carriers were significantly lower than those of Arg/Arg carriers in control group and in the high-risk group (all P < 0.05).

CONCLUSIONArg/Gln carriers were associated lower HDL-C levels in Han Chinese.

Adult ; Asian Continental Ancestry Group ; ethnology ; genetics ; Cholesterol, HDL ; blood ; Coronary Disease ; genetics ; Female ; Gene Frequency ; Genotype ; Ghrelin ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Risk Factors

OBJECTIVETo investigate the relationship between post-stenting coronary thrombolysis in myocardial infarction (TIMI) flow and plasma von Willebrand factor (vWF) and its cleaving protease (ADAMTS-13) levels in patients with ST segment elevation myocardial infarction (STEMI).

METHODSSTEMI patients who underwent primary percutaneous coronary intervention (PCI) and stenting between September, 2007 and December, 2009 were enrolled. According to the post-stenting TIMI flow, patients were divided to TIMI ≤ 2 group (n = 43) and TIMI 3 group (n = 43). Patients with chest pain or dyspnea and normal coronary angiographic results served as control group (n = 43). The levels of vWF and ADAMTS-13 were measured by ELISA at three time points: immediately after admission, beginning of PCI and 1 week after PCI.

RESULTSLevels of vWF in STEMI patients at all 3 time points were significantly higher than in control patients, and the level of vWF was significantly higher in TIMI ≤ 2 group than in TIMI 3 group [at admission: (6721.83 ± 1380.58) U/L vs. (4786.12 ± 2362.01) U/L, P < 0.05; at the beginning of PCI: (5744.65 ± 1240.71) U/L vs. (3011.33 ± 2270.40) U/L, P < 0.05 and at 1 week after PCI: (2001.48 ± 931.70) U/L vs. (1365.17 ± 724.12) U/L, P < 0.05]. ADAMTS-13 levels were similar among groups at admission and at beginning of PCI, however, the level of ADAMTS-13 at 1 week after PCI was significantly higher in TIMI ≤ 2 group than that in TIMI 3 group [(406.93 ± 101.44) mg/L vs. (270.34 ± 115.12) mg/L, P < 0.001]. Logistic regression analysis showed that both vWF at admission (OR = 1.917, P < 0.01) and vWF at the beginning of PCI (OR = 2.016, P < 0.01) were risk factors of TIMI ≤ 2.

CONCLUSIONIncreased vWF during peri-PCI periods was associated with post-stenting coronary TIMI ≤ 2 after primary PCI in STEMI patients, and the imbalance between vWF and ADAMTS-13 may thus play an important role in the development of slow flow post PCI.

ADAM Proteins ; blood ; ADAMTS13 Protein ; Aged ; Angioplasty, Balloon, Coronary ; Case-Control Studies ; Coronary Circulation ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; blood ; physiopathology ; therapy ; von Willebrand Factor ; metabolism

The aim of this study is to establish an HPLC method for simultaneous determinations of mifepristone and its metabolites, mono-demethylated mifepristone, di-demethylated mifepristone and C-hydroxylated mifepristone in plasma and to evaluate the pharmacokinetic characteristics of mifepristone tablet. Twenty healthy female Chinese subjects were recruited and a series of blood samples were collected before and after 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 12.0, 24.0, 48.0, 72.0 and 96.0 hours administration by a single oral dose of 75 mg mifepristone tablet. Mifepristone and its three metabolites were extracted from plasma using ethyl acetate and determined by high performance liquid chromatography. The main pharmacokinetic parameters of mifepristone and its metabolites, including Cmax, tmax, MRT, t(1/2), V, CL, AUC(0-96 h) and AUC(0-infinity), were calculated by Drug and Statistical Software Version 2.0. The simple, accurate and stable method allows the sensitive determinations of mifepristone and its metabolites in human plasma up to 4 days after oral administration of 75 mg mifepristone tablet and the clinical applications of their pharmacokinetic studies.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Biological Availability ; Chromatography, High Pressure Liquid ; methods ; Female ; Humans ; Mifepristone ; administration & dosage ; metabolism ; pharmacokinetics ; Tablets

Objective To investigate the epidemiological status and the anticoagulation treatment of atrial fibrillation (AF) patients,and to provide evidence for improving anticoagulation therapeutic effect in AF patients.Methods We performed a cross-sectional epidemiological investigation of 1 000 patients and out-patients with AF in Huashan Hospital.The clinical data including clinical feature,coexistent diseases,auxiliary examination,and treatment regimen of these patients were collected.The clinical features and anticoagulation status of AF patients were analyzed based on the stroke history,stroke risk evaluation and CHA2DS2-VASc score stratification.Results The mean age of these AF patients was (72.1 ± 11.1) years old.The most common coexistent diseases were hypertension (65％),coronary heart disease (32％) and diabetes (27％).About 6％ of the AF patients were diagosed with non-valvularatrial fibrillation (NVAF),and 22％ had stroke history.Patients were divided into two groups according to their stroke history.Compared with the non-stroke group,the stroke group was found to be older,with longer course of AF and poorer hypertension control.The overall anticoagulation rate was 32 ％ and antiplatelet rate was 46 ％.The anticoagulation rate of stroke group was 44％,higher than the non-stroke group (P＜0.001) but 78％ of these patients began anticoagulation therapy after the occurrence of stroke.When CHA2 DS2-VASc scores of NVAF patients were 2 to 5,the anticoagulation proportion increased gradually.When the scores were 2 to 6,the antiplatelet ratio increased gradually.But when the scores were 7-8 points,both anticoagulation and antiplatelet rates were in decline.Conclusions The anticoagulation rate in AF patients was still low at present,while relatively higher in patients with stroke.Anticoagulation could prevent stroke,AF patients still could benefit from anticoagulation after stroke,but anticoagulation before stroke could get more benefits.

To evaluate the therapeutic effect of Potentilla discolor on 2,4,6-trinitrobenzensulfonic acid(TNBS)-induced experimental ulcerative colitis(UC) in rats and to determine its therapeutic mechanism through mitochondrial autophagy, immune cells, and cytokines. A rat model of UC was established by TNBS-ethanol enema. Rats were divided into six groups: control, UC model, sulfasalazine(positive drug), and high-dose, moderate-dose, and low-dose ethanol extract groups. After 14-day continuous administration of the corresponding drugs, the disease activity index(DAI) and hematoxylin and eosin(HE) were evaluated. The morphological structure of mitochondria was observed by using transmission electron microscope(TEM), mitophagy-related mRNA expression was detected by using Real-time quantitative polymerase chain reaction(qRT-PCR), immune cell differentiation in rat serum was detected by using flow cytometry(FCM), and cytokine expression in colon tissues of rats was detected by protein microarray. The results showed that compared with the model group, each dose group of P. discolor could significantly reduce the DAI of UC model rats, and decrease the degree of inflammatory cells infiltration in the colon tissue of UC model rats. Meanwhile the expressions of T cells and Th cells in the serum increased significantly, the expression of Tc cells in the serum decreased significantly. Transmission electron microscope found that there was fusion of mitochondria and lysosomes in the colon tissue of the administration group. The expressions of mitochondrial autophagy related genes NF-κB, p62 and parkin were significantly increased in colon tissues. The results of protein chip showed that compared with the model group, the high dose group of P. discolor could significantly regulate the expression of cytokines. In conclusion, these results suggested that P. discolor improved TNBS-induced acute ulcerative colitis in rats by regulating the mitochondrial autophagy and the inflammatory factor expression.
Animals ; Autophagy ; Colitis, Ulcerative/genetics* ; Colon ; Mitochondria ; Potentilla/genetics* ; Rats