3,7-Bis(2-hydroxyethyl)icaritin, a potent inhibitor of phosphodiesterase-5, prevents monocrotaline-induced pulmonary arterial hypertension via NO/cGMP activation in rats.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH.

[Effects of nitrogen fertilizer application rate on nitrogen use efficiency and grain yield and quality of different rice varieties]. / æ°®è‚¥æ°´å¹³å¯¹ä¸åŒåŸºå› åž‹æ°´ç¨»æ°®ç´ åˆ©ç”¨çŽ‡ã€äº§é‡å’Œå“è´¨çš„å½±å“.

To provide scientific basis for reasonable application of nitrogen and create varieties with high N use-efficiency, an experiment was carried out to study the effects of nitrogen fertilizer application rate on grain yield, N use rate and quality of different rice varieties. Four different genotypic rice varieties, Nipponbare, N70, N178 and OM052 were used as tested material and three levels of nitrogen application rate (0, 120, 270 kg·hm-2) were conducted. Urea as nitrogen source was applied as basal (70%) and panicle (30%) fertilizer. The results showed that nitrogen fertilizer could raise yield mainly because of the increased effective panicles and filled grains per panicle. When the N application rate was 120 and 270 kg·hm-2, OM052 had the largest grain yield among four varieties, being 41.1% and 76.8% higher, respectively compared with control. Difference in grain yield among four varieties was due to the difference of nitrogen use efficiency. Under 120 and 270 kg·hm-2 nitrogen levels, Nipponbare had the lowest grain yield and N agronomic efficiency (NAE, 40.90 g·g-1 and 18.56 g·g-1), which was a variety with low N use-efficiency. On the contrary, OM052 had the highest grain yield and NAE (145.9 g·g-1 and 81.24 g·g-1), was a variety with high N use-efficiency. N fertilizer application increased the amylose content and protein content, lengthened gel consistency, reduced chalky kernel, chalkiness, and alkali digestion value. With the increase of N fertilizer application, hot paste viscosity, peak viscosity, consistence viscosity and breakdown viscosity were decreased gradually, and setback viscosity was increased. Correlation analysis showed that the yield and yield components had more significant correlations with appearance quality, cooking and eating quality under low N level. This study confirmed that OM052 was a double high variety with extremely high N agronomic efficiency and yield. Reasonable application of nitrogen fertilizer could significantly increase effective panicles and filled grains per panicle, improve rice quality, and ensure high yield and superior quality simultaneously.

A multicentre randomized clinical trial on efficacy and safety of huxin formula in patients undergoing percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) is widely used in clinical treatment of coronary artery disease. However, the effects of PCI on preventing restenosis after revascularization and improving the quality of life were not satisfying. Huxin Formula is formulated by modifying an experienced Chinese medicine formula and has been widely used in clinical practice due to its marked effects on coronary heart disease. A multicentre double-blind randomized controlled clinical trial was designed to evaluate the effects and safety of Huxin Formula in patients undergoing PCI. Our results showed that there was no significant difference between the two groups in main outcomes. For patients with ejection fraction (EF) >50%, score of the quality of life scale was higher in treatment group compared with control group. For patients with unstable angina, score of the quality of life scale in 360 days was significantly higher in treatment group compared with control group (P < 0.05). No obvious adverse reaction was found in the use of Huxin Formula. In conclusion, Huxin Formula, believed to be a safe treatment for patients after PCI, has benefits in improving the quality of life in patients with unstable angina though it failed to show superiority in primary and secondary outcomes.

Efficacy and safety of Huxin formula in patients after CABG: a multicenter, double-blind, randomized clinical trial.

BACKGROUND: Coronary artery bypass grafting (CABG) is widely used in the treatment of coronary artery disease. A multicenter, double-blind, randomized, controlled clinical trial was designed to evaluate the efficacy and safety of Huxin Formula post CABG. PATIENTS AND METHODS: 270 inpatients with coronary heart disease participated in this study. CABG patients in the control group were treated with placebo, while patients in the experimental group were treated with Huxin Formula 1 week after the surgery. All patients were treated for 6 months and followed up for another 6 months. The main outcomes (death, nonfatal myocardial infarction, repeat revascularization, and readmission) were assessed 360 days after treatment, and secondary outcomes (frequency and scores of angina pectoris, etc.) were assessed 0, 90, 180, 270, and 360 days after treatment. RESULTS: Our results showed no significant difference between the 2 groups for the primary endpoints. In patients with cardiac function class II (New York Heart Association), the score of angina pectoris was significantly lower (3.88 ± 3.86 vs. 5.45 ± 3.59) and the frequency of angina pectoris attacks was less (0.96 ± 1.01 vs. 1.36 ± 0.94) after 90 days of treatment with Huxin Formula compared to placebo (p < 0.05). In patients with 3 coronary vessel lesions, the cardiac function class (1.14 ± 0.35 vs. 1.05 ± 0.21) after 360 days was significantly higher in the control group compared to the treatment group (p < 0.05). There were no obvious adverse reactions. CONCLUSION: Huxin Formula may improve cardiac function of patients with 3 coronary vessel lesions and relieve symptoms of patients with cardiac function class II but failed to show superiority in primary outcomes.

Effect of Huxin Formula on reverse cholesterol transport in ApoE-gene knockout mice.

OBJECTIVE: To observe the effect of Huxin Formula on expressions of the chief reverse cholesterol transport (RCT) associated genes, caveolin-1 and scavenger receptor-BI (SR-BI) in ApoE-gene knockout [ApoE (-/-)] mice. METHODS: Thirty ApoE (-/-) mice of 4-6 weeks old were randomly divided into three groups (A-C). After being fed with high-fat diet for 16 weeks, they were treated with HXF (1 mL/100 g), pravachol (0.3 mg/100 g), and saline in equal volume respectively for 16 weeks successively; in addition, a blank group was set up with 10 C57BL/6J mice of 6-week old received 16-week high-fat feeding and saline treatment. Animals were sacrificed at the termination of the experiment, their paraffin sections of aortic tissue were used to measure the size of plaque, expressions of cavolin-1 and SR-BI were detected by immunological histochemical method. RESULTS: As compared with the blank group, levels of caveolin-1 and SR-BI were increased in Groups A and B (P<0.01); but the increase in Group A was more significant than that in Group B (P<0.05). The plaque/aorta area ratio decreased significantly in Groups A and B, but showed insignificant difference between the two groups. CONCLUSION: HXF could obviously increase the expressions of RCT associated genes, caveolin-1 and SR-BI, promote the RCT process, so as to reduce the formation of aorta atherosclerotic plaque in ApoE (-/-) mice.

Impact of C-reactive protein on in-stent restenosis: a meta-analysis.

We sought to evaluate the impact of C-reactive protein (CRP) levels on in-stent restenosis after percutaneous coronary intervention.The plasma level of CRP is considered a risk predictor for cardiovascular diseases. However, the relationship between CRP and in-stent restenosis has been a matter of controversy. Meta-analysis reduces variability and better evaluates the correlation.We performed a systemic search for literature published in March 2008 and earlier, using MEDLINE(R), the Cochrane clinical trials database, and EMBASE(R). We also scanned relevant reference lists and hand-searched all review articles or abstracts from conference reports on this topic. Of the 245 studies that we initially searched, we chose 9 prospective observational studies (1,062 patients).Overall, CRP concentration was higher in patients who experienced in-stent restenosis. The weighted mean difference in CRP levels between the patients with in-stent restenosis and those without was 1.67, and the Z-score for overall effect was 2.12 (P=0.03). Our subgroup analysis that compared patients with stable and unstable angina showed a weighted mean difference in the CRP levels of 2.22 between the patients with and without in-stent restenosis, and the Z-score for overall effect was 2.23 (P=0.03) in 5 studies of unstable-angina patients. There was no significance in 4 studies of stable-angina patients.In spite of significant heterogeneity across the studies, our meta-analysis suggests that preprocedurally elevated levels of CRP are associated with greater in-stent restenosis after stenting and that this impact appears more prominent in unstable-angina patients.

Prolonged hypercholesterolemia-induced tissue factor expression in rabbit vein grafts: a potential mechanism for graft failure.

OBJECTIVES: To evaluate tissue factor (TF) expression in vein grafts interposed in the arterial circulation of hypercholesterolemic rabbits. Veins implanted in the arterial circulation of normocholesterolemic rabbits respond by inflammation and infiltration by monocytes with transient TF expression. In a hypercholesterolemic milieu these monocytes may differentiate into macrophages capable of enhanced TF synthesis, which may facilitate hyperplasia and thrombosis. METHODS: Autologous jugular veins interposed in the carotid artery of hypercholesterolemic rabbits were harvested at 1, 2, 4, 6, and 8 weeks after surgery and examined for presence and localization of rabbit TF antigen. Protein extracted from vein segments was evaluated for procoagulant activity by bioassay and for TF protein content by western blotting. RESULTS: Rabbit TF antigen was observed mostly in the subendothelium of vein grafts. Peak TF procoagulant activity observed at 1-2 weeks postsurgery (2.3+/-1.8 pg/mg, P<0.006) declined to 0.9+/-0.5, 0.2+/-0.1, and 0.15+/-0.06 pg/mg at 4, 6, and 8 weeks, respectively (P<0.03). Western blotting showed a time-dependent pattern for rabbit TF protein with prolonged expression peaking at 6 weeks. CONCLUSION: Prolonged expression of biologically active rabbit TF and TF protein were shown within jugular vein grafts of hypercholesterolemic rabbits. This response, reported for the first time and attributed to increased cholesterol levels, may possibly contribute to enhanced hyperplasia. These results suggest that TF expression could serve as another mechanism underlying vein graft failure and that hypercholesterolemia in bypass patients should be treated aggressively beginning within the weeks after surgery.

[Study on the inclusion of volatile oil extracted from Herba Pogostemonis and Exocarpium citri by beta-cyclodextrin].

OBJECTIVE: To investigate the inclusion technology conditions of volatile oil extracted from Herba Pogostemonis and Exocarpium citri in Huxin Fang granules by beta-cyclodextrin. METHODS: The orthogonal design was used. The percent conversion of the oil in inclusion and the yield of inclusion complex were the indices to determine the factors containing the ratio of the oil to beta-cyclodextrin, the ratio of beta-cyclodextrin to water and the grinding time of the mixture of the oil, beta-cyclodextrin and water. RESULTS: The optimum conditions for the inclusion were as follows: the ratio of the oil to beta-cyclodextrin was 1:10, the ratio of beta-cyclodextrin to water was 1:3, and the grinding time was 40 min. CONCLUSION: The optimum conditions for the inclusion were steady and feasible.

[Systematic review of randomized controlled trials on preventing and treating restenosis after percutaneous coronary intervention with Chinese medicine].

OBJECTIVE: To evaluate the randomized controlled trials on preventing and treating restenosis after percutaneous coronary intervention (PCI) with Chinese medicine adopting the principle of evidence-based medicine (EBM). METHODS: Pertinent literatures were retrieved roundly, and scored depending on Jadad Quality Scale. Meta-analysis was applied on the total effect of outcomes reported using RevMan 4. 2 software. Moreover, the sensitivity was analyzed, the publication bias was identified with funnel-plot and the adverse reaction of medicine was reported. RESULTS: Among the 17 literatures met the inclusion criteria, only two double-blinded trials were appraised as high quality. The analysis on the recurrence rates of restenosis post-PCI and angina pectoris in patients treated with Chinese medicine illustrated that the rates in the treatment group were all lower than those in the control group with statistical significance (P < 0.01). Sensitivity analysis revealed a relatively stable result of the evaluation. Funnel-plot displayed an asymmetrical figure, indicating the possible existence of publication bias. CONCLUSION: TCM has definite therapeutic effect on preventing and treating restenosis after PCI and reducing the recurrence rate of angina pectoris in patients.

[Progress of study on applying traditional Chinese medicine and drugs in cardiac surgery].

Application of traditional Chinese medicine and drugs in cardiac surgery have won great progress in recent 10 years, mainly presented in aspects of the treatment of coronary heart disease, myocardium protection, cardiopulmonary bypass and pulmonary hypertension.

[Effect of abdominal needling in treating post-cardiosurgical operational gastrointestinal dysfunction].

OBJECTIVE: To evaluate the clinic effect of abdominal needling (AN) on post-cardiosurgical operational gastrointestinal dysfunction. METHODS: Sixty patients were equally assigned to two groups, the AN group and the control group. AN applied on the AN group was conducted by needling at Xiawan (Ren 10), Qihai (Ren 6), Qipang, Guanyuan (Ren 4), Qixue, Shuifen (Ren 9), Tianshu (St. 25) and Daju (St. 27), starting from the first day after operation, once every day with the needle retained time of 20 min, 5 days as one therapeutic course. The control group was treated with the conventional post-operational measurement with intravenous injection of 20 mg Omeprazole once a day, for 3 successive days. The score on symptoms as anorexia, weakness, abdominal distension, constipation, laziness to speak, nausea and vomiting, weakened borborygmus, pale-yellow complexion and edema, etc. , were observed. RESULTS: The symptom scores in the aspects of anorexia, weakness, abdominal distension, constipation, weakened borborygmus, nausea and vomiting in the AN group were significant difference when compared with before treatment and the control group (P <0.01). After treatment the improvement in the control group only showed in weakness and pale-yellow complexion (P <0.01). Observation on gastric emptying showed that 24 h gastric paresis occurred in 17 patients (56.7%) of the AN group, and 22 (73.3%) of the control group; the 24 h and 72 h barium residue (strip) in the AN group was 10.60 +/- 4.61 and 8.53 +/- 4.08 respectively, while in the control group 17.07 +/- 3.99 and 15.83 +/- 4.19; the 24 h, 72 h gastric emptying rate in the former was (47.00 +/- 23.07) % and (57.33 +/- 20.37) %, and in the latter (14.67 +/- 19.95) % and (20.83 +/- 20.97) %, all showed significant difference between them (P <0.05 or P <0.01). Levels of motilin in the two groups after operation were decreased showing significant difference in comparison with before operation (P < 0.01), and AN group was raised after teratment, also showing significant difference between groups (P <0.01). CONCLUSION: AN can strengthen gastrointestinal peristalsis, promote gastrointestinal emptying, recover quickly gastrointestinal hormone to the normal range. Besides, it is safe and effective, with no pain or only slight pain, easy in locating the acupoint accurately, standard prescription, high compliance of patients, and convenient for clinical operating, therefore, it is worthy of spreading in clinical practice.

[Cluster analysis on TCM syndromes in 319 coronary artery disease patients for establishment of syndrome diagnostic figure].

OBJECTIVE: To explore the diagnostic figures for TCM syndrome typing in coronary heart disease (CHD) patients. METHODS: A retrospective investigation was carried out in 319 CHD patients hospitalized from Jan. 2004 to Dec. 2004 in authors' hospital. Through cluster analysis, descriptive statistics and frequency normalization in combination of clinical observation, the diagnostic figures of TCM syndromes were obtained. RESULTS: The figures for qi deficiency syndrome were: primary symptoms: chest pain and stuffiness, secondary symptoms: tiredness, short breath, poor appetite, light colored tongue, deep and thready pulse; for qi deficiency with phlegm and blood stasis syndrome: primary symptoms: chest stuffiness and pain, secondary symptoms: tiredness, insomnia, palpitation, obesity, dark red tongue, string and slippery pulse; for turbid-phlegm blocking collateral syndrome: primary symptoms: chest stuffiness, secondary symptoms: cough, expectoration with much white sputum, tiredness, short breath and poor appetite, light colored tongue with white greasy coating, slippery pulse. CONCLUSION: Research on diagnostic criteria for TCM syndrome typing could be established upon clinical epidemiologic survey and statistic analysis in combining with specialists' suggestions to primarily set the referrence figures.

[Analysis on TCM syndrome distribution laws in 319 patients with coronary heart disease].

OBJECTIVE: To study TCM syndrome distribution laws in patients with coronary heart diseases (CHD) by epidemiological investigation. METHODS: A clinical survey was carried out in 319 inpatients with CHD, whose diagnosis was confirmed by coronary arteriography, in the authors' hospital from January 2004 to December 2004. The TCM syndrome distribution laws were analyzed, and the relationship of coronary arteriographic picture with TCM syndrome elements, common symptoms, pulse and tongue figures, as well as the correlation between syndrome typing and blood-lipid levels were analyzed, too. RESULTS: Qi deficiency was the most popular syndrome in patients with CHD (87.1%), blood stasis syndrome and phlegm retention syndrome took the second place, accounting for 79.9% and 78.7% respectively. No significant difference was shown in comparison of tongue and pulse figures with the affected branches of coronary artery, the dark-pale tongue with white greasy fur and taut-slippery pulse being the dominance in patients. The blood-lipid levels in patients with various TCM syndrome types were similar, showing insignificant difference. CONCLUSION: The TCM pathogenesis of CHD takes qi deficiency as the core, blood stasis and phlegm retention as the important pathologic products.

[Effects of shenfu injection on immune function in patients during perioperative cardiopulmonary bypass].

OBJECTIVE: To observe the effects of Shenfu Injection (SI) on immune function in patients during perioperative cardiopulmonary bypass (CPB). METHODS: Ninety patients scheduled for CPB were randomly divided into 3 groups, the group A treated with SI before CPB, the group B treated with SI after CPB and the group C (the control group), 30 cases in each group. Counts of leukocyte, neutrophil, lymphocyte and T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) and serum levels of IgG, IgA, IgM, C3 and C4 were investigated at different time-points, i.e. one day before CPB, immediately after anesthesia and finishing CPB, and the 1st, 3rd and 8th post-operational days. RESULTS: In all the three groups, counts of leukocyte and neutrophil rose immediately after CPB and the high level maintained on the 1st and 3rd post operational days, it somewhat lowered on the 8th day but still higher than that before operation, showing insignificant difference among the 3 groups. As for the other indexes, they declined obviously and immediately after CPB and began to restore on the 8th day to a certain extent, and the restoration were better in the group A and B, as the changes were milder. CONCLUSION: SI could improve the immune function and reduce the risk of post operational infection in patients during perioperative CPB.

[Clinical efficacy of treatment for regulating Pi and protecting Xin in treating patients after coronary artery bypass grafting and its effect on patients' quality of life].

OBJECTIVE: To evaluate the clinical efficacy of treatment for regulating Pi and protecting Xin (abbr. as CHM) and its effect on quality of life (QOL) in patients after coronary artery bypass grafting (CABG). METHODS: One hundred and six patients, who were planned to undergo CABG were assigned into two groups, the 51 patients in the control group were treated with conventional Western medicinal treatment (WM) and the 55 patients in the experimental group were treated by WM with additional medication of CHM constituted mainly by modified Huxin Recipe. The changes of symptoms and heart function were observed and the patients' QOL was evaluated by SF-36 Scale. RESULTS: After being treated for 3 months, the total scores of symptoms in the experimental group was significantly improved in comparing with that in the control group (P < 0.01), the clinical efficacy on symptoms of TCM and improvement of heart function were superior to those in the control group (P < 0.05) respectively. The scores in terms of pain, vitality, role of emotion, mental health, health transition of patients in the experimental group according to SF-36 scale were significantly higher than those in the control group (P < 0.05 or P < 0.01). CONCLUSION: Treatment for regulating Pi and protecting Xin by modified Huxin Recipe can improve the recovery process of patients after CABG, elevate patients' heart function, symptoms and QOL.

[Clinical observation on quality of life in coronary artery bypass grafting patients treated according to syndrome differentiation of TCM].

OBJECTIVE: To evaluate the clinical effect and quality of life (QOL) in coronary artery bypass grafting (CABG) patients treated according to syndrome differentiation of TCM. METHODS: Eighty-two CABG patients were allocated in the control group (n = 39) treated with conventional method of western medicine, and the TCM-treated group (n = 43) treated according to syndrome differentiation of TCM based on the conventional western medicine. The Seattle Angina Questionnaire (SAQ) was used to assess the clinical effect and quality of life. RESULTS: After 2 months treatment, the TCM syndrome score in TCM-treated group was better, and the score of SAQ was higher than that in the control group (all P < 0.01). In the aspects of anginal stability, anginal frequency, treatment satisfaction and disease perception, there was significant difference between the two groups (P < 0.05 or P < 0.01). CONCLUSION: TCM treatment could promote recovery, improve symptoms and elevate QOL of CABG patients.