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Salvianolic acid A (SAA), a water-soluble phenolic acid isolated from the root of Dan Shen, displays distinct antioxidant activity and effectiveness in protection against cerebral ischemia/reperfusion (I/R) damage. However, whether SAA can enter the central nervous system and exert its protective effects by directly targeting brain tissue remains unclear. In this study, we evaluated the cerebral protection of SAA in rats subjected to transient middle cerebral artery occlusion (tMCAO) followed by reperfusion. The rats were treated with SAA (5, 10 mg/kg, iv) when the reperfusion was performed. SAA administration significantly decreased cerebral infarct area and the brain water content, attenuated the neurological deficit and pathology, and enhanced the anti-inflammatory and antioxidant capacity in tMCAO rats. The concentration of SAA in the plasma and brain was detected using LC-MS/MS. A pharmacokinetic study revealed that the circulatory system exposure to SAA was equivalent in the sham controls and I/R rats, but the brain exposure to SAA was significantly higher in the I/R rats than in the sham controls (fold change of 9.17), suggesting that the enhanced exposure to SAA contributed to its cerebral protective effect. Using a GC/MS-based metabolomic platform, metabolites in the serum and brain tissue were extracted and profiled. According to the metabolomic pattern of the tissue data, SAA administration significantly modulated the I/R-caused perturbation of metabolism in the brain to a greater extent than that in the serum, demonstrating that SAA worked at the brain tissue level rather than the whole circulation system. In conclusion, a larger amount of SAA enters the central nervous system in ischemia/reperfusion rats to facilitate its protective and regulatory effects on the perturbed metabolism.

To investigate the relationship between free triiodothyronine (FT3) and the international normalized ratio (the ratio of the prothrombin time of a patient to the normal sample, INR) in Chinese euthyroid subjects with acute ST-segment elevation myocardial infarction (STEMI).A total of 231 consecutive patients (177 males, 54 females) with STEMI were enrolled. Anthropometric and laboratory measurements, including heart rate, respiratory rate, blood pressure, body temperature, platelet count, INR, prothrombin time, activated partial thromboplastin time, FT3, free thyroxine (FT4), and thyroid-stimulating hormone, were collected from all the patients. The levels of FT3 and FT4 were measured with a full-automatic immune analyzer. The INR was determined using a coagulation analyzer.Patients were classified into 4 groups according to their quartile FT3 and FT4 levels: 0.40-3.09 (n=52), 3.10-3.69 (n=56), 3.70-4.29 (n=64) and 4.30-7.10 (n=59) for FT3; 4.9-14.8 (n=57), 14.9-16.8 (n=58), 16.9-18.7 (n=57) and 18.8-29.0 (n=59) for FT4. Subjects with a high FT3 level had significantly lower values of INR than those with a low FT3 level (P=0.01). Multiple linear regression analysis revealed decreased serum FT3 as an independent risk factor for elevated INR values (β=-0.139, P=0.025). The value of INR was similar among the 4 groups according to the quartile FT4 levels (P=0.36).Free triiodothyronine was negatively associated with INR in the patients with acute STEMI and normal thyroid function.

To investigate the SLCO1B1 388AG and 521TC polymorphisms in hyperlipidemia patients and evaluate the effect of the two polymorphisms on the lipid-lowering efficacy of pitavastatin.The functional polymorphisms of SLCO1B1 (388AG and 521TC) were genotyped in 140 Chinese patients with essential hyperlipidemia using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and one-step tetra-primers ARMS-PCR. Eighty-five patients were enrolled in the clinical trial and given 2 mg of pitavastatin daily for 8 weeks. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) serum levels were measured at baseline, after 4 weeks and after 8 weeks of treatment.The allele frequencies of SLCO1B1 388AG and 521TC in essential hyperlipidemia patients were 71.1% and 11.1%, respectively. The 4- and 8-week treatment with pitavastatin significantly reduced TC, TG, and LDL levels, but there was no statistical difference among patients with wild type, SLCO1B1 388AG or SLCO1B1 521TC in the lipid-lowering efficacy of pitavastatin.The present study found that the allele frequencies of SLCO1B1 388AG and 521TC in Chinese patients with essential hyperlipidemia are comparable to those in healthy Chinese population. SLCO1B1 388AG and 521TC do not affect the lipid-lowering efficacy of pitavastatin.

The aim of this study was to test the hypothesis that lower serum sodium may be associated with increased cardiovascular events and all-cause mortality by means of long-term follow-up of subjects with coronary atherosclerosis in a prospective, hospital-based epidemiological study in China. A prospective, hospital-based epidemiological design was used. The study population consisted of 1069 consecutive patients who were scheduled to undergo coronary angiography for suspected or known coronary atherosclerosis. The severity of coronary atherosclerosis was defined using Gensini's score system. Age, sex-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the quartiles of serum sodium concentration were estimated with Cox proportional hazard models, using quartile 1 as the reference. Cox proportional hazard models were also constructed to estimate the hazard ratios and 95% confidence intervals for all-cause mortality and final end-point events by serum sodium quartile and to adjust for potentially confounding variables. Multivariate models were adjusted for the following variables: age, sex, smoking status, alcohol consumption, body mass index, blood pressure, potassium, chloride, total cholesterol, triglycerides, fasting blood glucose, urea, creatinine, uric acid, and Gensini's score. During the median 2.86 years (3011.66 person-years) of follow-up, 176 final end-point events were documented. These events included 79 deaths and 97 readmissions for coronary heart disease. There was a statistically significant inverse association of serum sodium with all-cause mortality (P

Aim: To explore the relationship between serum sodium concentration and coronary atherosclerosis. Methods: The study population consisted of 896 consecutive patients (684 males and 212 females) who underwent coronary angiography for suspected or known coronary atherosclerosis. Smoking and drinking were investigated. The anthropometric measurements, including body mass index, systolic blood pressure and diastolic blood pressure, and the serum measurements, including sodium, potassium, chlorine, lipids, blood glucose, urea, creatinine, and uric acid for every patient were conducted. The severity of coronary atherosclerosis was defined by the Gensini score system. The statistical methods, including one-way ANOVA, Kruskal-Wallis test, Spearman correlation analysis, partial correlation analysis, multivariate stepwise linear regression analysis, and multinomial logistic regression analysis were employed to explore the relationship between serum sodium concentration and the Gensini score. Results: The analysis of the Kruskal-Wallis test indicated that the distribution of the Gensini score ( P =0.000) differed among the groups according to serum sodium concentration, quartile values of which were used as cut-off points. The Spearman correlation and partial correlation analysis controlling for gender, smoking status, and drinking status indicated that the Gensini score significantly correlated with the sodium concentration ( r =-0.241, P =0.000 for the Spearman correlation, r =-0.114, P =0.000 for the partial correlation). The results from the multivariate stepwise linear regression analysis showed that the left ventricular ejection fraction (β=-0.228, P =0.000), age (β=0.137, P =0.010), glucose level (β=0.129, P =0.000), and sodium level (β=-0.106, P = 0.004) were significantly and independently associated with the Gensini score. The results of the multinomial logistic regression analysis suggested that the hyponatremia was the risk factor for the higher Gensini score. Conclusion: The serum sodium concentration was significantly and negatively associated with the Gensini score; and the actual mechanism underlying the association needs further study.

To study the effect of adenovirus5-mediated human hepatocyte growth factor (Ad5-HGF) transfer on post-infarct heart failure in a swine model. Twelve young Suzhong swine were randomly divided into 2 groups: the Ad5-HGF group (n=6) and the null-Ad5 group (n=6). Four weeks after left anterior descending coronary artery (LAD) ligation, Ad5-HGF was transferred into the myocardium via the right coronary artery. Coronary angiography and gated cardiac perfusion imaging were performed at the end of 4 and 7 weeks after LAD ligation, respectively, to evaluate collateral artery growth and cardiac perfusion. Then all animals were killed, the expression of HGF and α-smooth muscle actin (α-SMA) were evaluated by enzyme-linked immunosorbent assay and immunohistochemistry. Compared with the null-Ad5 group, higher expression of human HGF was observed in the myocardium in the Ad5-HGF group (109.3±7.8 vs 6.2±2.6, t=30.685, P

Aim: Genetic polymorphisms causing Ser49Gly and Gly389Arg mutants of β 1 - adrenoceptor may result in significant changes in the function of this receptor. The aim of the present study was to investigate the frequencies of the Ser49Gly and Gly389Arg mutant alleles in healthy Chinese populations and to investigate the differences between 2 Chinese ethnic groups (Han and Dai populations) with respect to the frequencies of these alleles. Methods: A total of 225 Han Chinese and 175 Dai Chinese unrelated healthy volunteers were recruited for this study. Genomic DNA was extracted from peripheral blood leukocytes by using a standard manual chloroform-phenol extraction. Fragments spanning the 2 polymorphisms were amplified by using polymerase chain reaction with template genomic DNA and relevant primers. The DNA products including the polymorphic loci were subjected to restriction endonuclease digestion with Eco 0109I and Bcg I. Digested fragments were detected with an ultraviolet detector after electrophoresis (100 V for approximately 1.5 h). Results: The frequencies of the Gly49 and Arg389 alleles were, respectively, 16.2% and 76.4% in the Han population and 14.6% and 75.7% in the Dai population. Conclusion: The polymorphisms causing the Ser49Gly and Gly389Arg mutations of the β 1 -adrenoceptor existed in both healthy Han and Dai Chinese populations. The frequencies of the Ser49Gly and Gly389Arg mutant alleles were not significantly different in the Han and Dai populations. However, the frequency of the Gly389 variant seems to be significantly lower in these 2 populations than in an African-American population.

Aim: To explore the relationship between differential leucocyte count and coronary atherosclerosis. Methods: The study population consisted of 507 consecutive patients (376 male and 131 female) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' smoking and drinking habits were investigated, and anthropometric measurements, serum measurements, and hematological measurements were conducted for every patient. The severity of coronary atherosclerosis was defined by using Gensini's score system. One-way ANOVA, Spearman's correlation analysis, and multivariate stepwise linear regression analysis were employed to explore the relationship between differential leucocyte count and coronary atherosclerosis. Results: Oneway ANOVA indicated that the diastolic blood pressure, glucose, urea, creatinine, leukocyte count, neutrophil count, monocyte count, hemoglobin, and platelet count differed among the groups according to Gensini's score, the tertile values of which were used as cutoff points. Spearman's correlation analysis suggested that Gensini's score was significantly correlated with age, diastolic blood pressure, glucose, urea, creatinine, leukocyte count, neutrophil count, monocyte count, hemoglobin, and erythrocyte count, respectively. Multivariate stepwise linear regression analysis show that neutrophil count (beta=0.247, P =0.000), age (beta=0.141, P =0.001), glucose (beta=0.173, P =0.000), creatinine (beta=0.088, P =0.063), hemoglobin (beta=-0.168, P =0.013) and sex (men were coded as 1 and women were coded as 2; beta=-0.121, P =0.012) were significantly independently associated with the Gensini's score. Conclusion: The independent association of neutrophil count with the angiographical characteristics of coronary atherosclerosis, as estimated by Gensini's score, strongly suggests that granulocytosis may play a role in the development of coronary atherosclerosis.

Aim: To explore the potential interactions between Yin Zhi Huang (YZH) and omeprazole, a substrate of CYP3A4 and CYP2C19. Methods: Eighteen healthy volunteers, including 6 CYP2C19*1 /* 1 , 6 CYP2C19*1 /* 2 or * 3 and 6 CYP2C19*2 /* 2 were enrolled in a 2-phase, randomized, crossover clinical trial. In each phase, the volunteers received either placebo or 10 mL YZH oral liquid, 3 times daily for 14 d. Then all the patients took a 20 mg omeprazole capsule orally. Blood samples were collected up to 12 h after omeprazole administration. Plasma concentrations of omeprazole and its metabolites were quantified by HPLC with UV detection. Results: After 14 d of treatment of YZH, plasma omeprazole significantly decreased and those of omeprazole sulfone and 5-hydroxyomeprazole significantly increased. The ratios of the area under the plasma concentration-time curves from time 0 to infinity (AUC (0-infinity) of omeprazole to 5-hydroxyomprazole and those of omeprazole to omeprazole sulfone decreased by 64.80%plusminus12.51% ( P =0.001) and 63.31%plusminus18.45% ( P =0.004) in CYP2C19*1/*1, 57.98%plusminus14.80% ( P =0.002) and 54.87%plusminus18.42% (P =0.003) in CYP2C19*1/*2 or *3 , and 37.74%plusminus16.07% ( P =0.004) and 45.16%plusminus15.54% ( P =0.003) in CYP2C19*2/*2 , respectively. The decrease of the AUC (0-infinity) ratio of omeprazole to 5-hydroxyomprazole in CYP2C19*1/*1 and CYP2C19*1/*2 or *3 was greater than those in CYP2C19*2/*2 ( P =0.047 and P =0.009). Conclusion: YZH induces both CYP3A4-catalyzed sulfoxidation and CYP2C19-dependent hydroxylation of omeprazole leading to decreases in plasma omeprazole concentrations.

To explore the relationship between differential leucocyte count and coronary atherosclerosis.The study population consisted of 507 consecutive patients (376 male and 131 female) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' smoking and drinking habits were investigated, and anthropometric measurements, serum measurements, and hematological measurements were conducted for every patient. The severity of coronary atherosclerosis was defined by using Gensini's score system. One-way ANOVA, Spearman's correlation analysis, and multivariate stepwise linear regression analysis were employed to explore the relationship between differential leucocyte count and coronary atherosclerosis.One-way ANOVA indicated that the diastolic blood pressure, glucose, urea, creatinine, leukocyte count, neutrophil count, monocyte count, hemoglobin, and platelet count differed among the groups according to Gensini's score, the tertile values of which were used as cutoff points. Spearman's correlation analysis suggested that Gensini's score was significantly correlated with age, diastolic blood pressure, glucose, urea, creatinine, leukocyte count, neutrophil count, monocyte count, hemoglobin, and erythrocyte count, respectively. Multivariate stepwise linear regression analysis show that neutrophil count (beta=0.247, P=0.000), age (beta=0.141, P=0.001), glucose (beta=0.173, P=0.000), creatinine (beta=0.088, P=0.063), hemoglobin (beta=-0.168, P=0.013) and sex (men were coded as 1 and women were coded as 2; beta=-0.121, P=0.012) were significantly independently associated with the Gensini's score.The independent association of neutrophil count with the angiographical characteristics of coronary atherosclerosis, as estimated by Gensini's score, strongly suggests that granulocytosis may play a role in the development of coronary atherosclerosis.