Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction / 中国药理学与毒理学杂志

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. METHODS The patients with coronary heart dis?ease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months, and the changes of cardiac function were observed. 61 serum samples (including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group) were analyzed by non labeled proteomics. The disease group was used as the control group, and the protein with expression level difference of more than 1.2 folds (P<0.05) was screened. The molecular function, biologi?cal pathway and protein interaction of the different proteins were analyzed by bioinformatics, so as to identify the molecu?lar and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction, regulate blood glucose and blood lipid levels, prolong thrombin time, and improve heart function. The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group. Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1, alpha-2 and other proteins to act on HDL assembly, platelet degradation, PI3K Akt signaling pathway, and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome. CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syn?drome of coronary heart disease. It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins. This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

Analysis of Medication Rules of Coronary Heart Disease with Heart Failure of Qi Deficiency and Blood Stasis Syndrome Based on Literature Research / 中国实验方剂学杂志

Objective:To systematically sort out and summarize the medication rules of clinical prescriptions for coronary heart disease with heart failure of Qi deficiency and blood stasis syndrome，and to provide reference for selecting prescriptions and medications for the treatment of coronary heart disease （CHD） with traditional Chinese medicine （TCM）. Method:All relevant literature concerning the treatment of CHD with compound TCM prescriptions for Qi deficiency and blood statis syndrome from 2000 to 2020 were retrieved from the China National Knowledge Network （CNKI），WanFang database （WanFang），and VIP journal database （VIP），and the names of prescriptions and drug components were extracted，followed by the frequency of drug use and drug category. Association rules of high-frequency drugs were analyzed by SPSS 18.0，and systematic clustering analysis was conducted by SPSS 21.0. Result:Finally，41 qualified literature articles covering 35 prescriptons and 66 drugs were included in the study. The total frequency of the drugs was 433 times. Among them，there were a total of 25 traditional Chinese medicines with a frequency of ≥5 times. The top 3 frequently used Chinese medicines were Astragali Radix （8.8%），Salviae Miltiorrhizae Radix et Rhizoma （7.2%），Chuanxiong Rhizoma （5.8%）. A total of 15 types of drugs were involved，among which tonic drugs （31.4%），blood promoting and blood stasis drugs （28.2%），and hydration and dampening drugs （7.6%） were used most frequently. The association rule analysis of traditional Chinese medicines with frequency of ≥ 5 showed that there were 13 pairs of binomial associations in 25 traditional Chinese medicines，with Astragali Radix in combination with Salviae Miltiorrhizae Radix et Rhizoma，Chuanxiong Rhizoma，Carthami Flos，et al. There were 8 groups of three associations，with Astragali Radix，Salviae Miltiorrhizae Radix et Rhizoma，and Chuanxiong Rhizoma as the main combinations. A systematic clustering analysis showed that the clustering effect was best when the 25 traditional Chinese medicines were clustered into 5 categories. Conclusion:The treatment of coronary heart disease with heart failure of Qi deficiency and blood stasis syndrome is based on replenishing qi and activating blood circulation，supplemented by warming yang，diuresis，and phlegm-resolving drugs，which can enhance the clinical efficacy. Two basic prescriptions of Buyang Huanwutang and Si junzitang are extracted. Other combinations of prescriptions and drugs can provide references for the clinical treatment of coronary heart disease with heart failure.

Correlations Between Severity of Heart Failure Related to Coronary Heart Disease of Qi Deficiency and Blood Stasis Syndrome and Biological Indexes / 中国实验方剂学杂志

Objective:To explore the correlations of the severity of heart failure related to coronary heart disease arising from Qi deficiency and blood stasis with cardiac function indexes， energy metabolism indexes， coagulation function indexes， and inflammatory factors， in order to provide a scientific basis for further research on the biological foundation of this disease. Method:Two hundred patients with heart failure related to coronary heart disease of Qi deficiency and blood stasis syndrome were collected and then classified into mild， moderate and severe groups according to their scores of Qi deficiency and blood stasis syndrome. Meanwhile， 40 healthy persons confirmed by physical examination during the same period were included into the control group. Such biological indexes as cardiac function indexes， energy metabolism indexes， coagulation function indexes， and inflammatory factors were determined in patients of each group for comparison. Then the Spearman rank correlation analysis was conducted to figure out the correlations between differential indexes and the severity of Qi deficiency and blood stasis syndrome， followed by the determination of risk factors for the severity of Qi deficiency and blood stasis syndrome by ordered logistic regression analysis. Result:The cardiac function indexes， energy metabolism indexes， coagulation function indexes， and inflammatory factors in patients with heart failure related to coronary heart disease arising from Qi deficiency and blood stasis varied significantly. There were significant statistical differences in the levels of N-terminal pro-B-type natriuretic peptide （NT-ProBNP）， 6-minute walk test （6MWT）， heart-type fatty acid-binging protein （H-FABP）， prothrombin time （PT）， activated partial thromboplastin time （APTT）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， and nitric oxide （NO） among the mild， moderate， and severe groups （<italic>P</italic><0.05）. The severity of Qi deficiency and blood stasis syndrome was positively correlated with NT-ProBNP （<italic>r</italic>=0.144）， PT （<italic>r</italic>=0.173）， and APTT （<italic>r</italic>=0.144）， but negatively with 6MWT （<italic>r</italic>=-0.287）. The 6MWT［odds ratio（OR）=0.995， 95% confidence interval（CI） 0.991-0.998），<italic>P</italic><0.01］ and APTT（OR=1.088，95%CI 1.021-1.157，<italic>P</italic><0.01） were independent risk factors affecting the severity of heart failure related to coronary heart disease arising from Qi deficiency and blood stasis. Conclusion:The severity of heart failure related to coronary heart disease of Qi deficiency and blood stasis syndrome is closely related to NT-ProBNP， 6MWT， H-FABP， PT， APTT， TNF-<italic>α</italic>， and NO. Moreover， 6MWT and APTT can be used as independent risk factors to evaluate the severity of patients with heart failure related to coronary heart disease due to Qi deficiency and blood stasis.

Key points of post-marketing evaluation of classic traditional Chinese medicine prescriptions based on combination of disease and syndrome / 中国中药杂志

Classic prescriptions, hospital preparations and famous traditional Chinese medicine(TCM) experience prescriptions are the main sources of new drug development and innovation. The multi-components and multi-targets treatment characteristics of TCM are advantages, but at the same time, broad indications, unclear clinical positioning and lack of evidence-based evidence support are the key problems affecting the play of TCM efficacy and restricting its promotion and application. The hot in recent research was to how to break through the bottleneck, precise clinical positioning, highlight the advantages of the classic TCM prescriptions, and complete the transformation from clinical practice, clinical research to clinical evidence, but at the same time, it is also the difficulty. The clinical research model of the combination of disease and syndrome can fully reflect the ancient medical case evidence of classic TCM prescriptions, the historical experience of human used and the characteristics of syndrome differentiation and treatment, and highlight the advantages of Chinese medicine. At the same time, under the modern disease classification system and research mode, is conducive to established the standardized clinical evidence report and evaluation system, is conducive to promote the integration of clinical research evidence, and avoids excessive attenuation of information. Based on the previous work of our team, the intention of this study was to make a comment about the key points of the post-marketing evaluation of the classic TCM prescriptions under the combination of disease and syndrome and includes key points:(1)With the syndrome as the carrier, connected with the classical prescription and clinical diseases, focused on the clinical positioning on macroscopically.(2)The combination of syndrome visualization, standardization and pharmacological molecular basis, focus on clinical precise positioning in microscopic.(3)Innovating therapeutic effect evaluation methods, reflecting the curative effect characteristics based on syndrome differentiation.(4)The combination of "randomized controlled evidence-based studies" and "real world evidence-based evaluation", focusing on clinical advantages, fully evidence-based evidence.(5)Make full use of clinical registration studies and pay attention to safety.

Systematic evaluation and trail sequential analysis of efficacy and safety of Yangxue Qingnao Granules in treatment of essential hypertension and its accompanying symptoms / 中国中药杂志

To systematically evaluate the efficacy and safety of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms. PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, and China biomedical database(CBD) were searched to screen out from the establishment of the database to April 2020 about the clinical randomized controlled trials of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and accompanying symptoms. The articles were selected according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. TSA 0.9.5.10 Beta software was used for sequential analysis, and GRADE 3.6 was used for evidence quality evaluation. A total of 4 532 patients were included in 34 randomized controlled trials. Meta-analysis results showed that: Yangxue Qingnao Granules combined with conventional anti-hypertensive agents reduced systolic blood pressure(MD=-10.56, 95%CI[-13.63,-7.50], P<0.000 01) and diastolic blood pressure(MD=-8.21, 95%CI[-10.84,-5.59], P<0.000 01), improved total effective rate(RR=1.21, 95%CI[1.14, 1.29], P<0.000 01), improved patients dizziness(RR=1.29, 95%CI[1.21, 1.37], P<0.000 01), insomnia(RR=1.66, 95%CI[1.44, 1.91], P<0.000 01), headache(RR=1.32, 95%CI[1.21, 1.43], P<0.000 01), chest distress(RR=1.26, 95%CI[1.12, 1.42], P=0.000 1), memory loss(RR=1.24, 95%CI[1.10, 1.40], P=0.000 4), palpitation(RR=1.28, 95%CI[1.17, 1.41], P<0.000 01), and improved traditional Chinese medicine symptom scores(MD=-4.24, 95%CI[-5.25,-3.23], P<0.000 01) and headache symptom improvement scores(MD=-2.02, 95%CI[-2.51,-1.53], P<0.000 01) as compared with Western medicine group alone. Subgroup analysis results showed that Yang-xue Qingnao Granules combined with ACEI drug had more obvious effects in lowering systolic blood pressure and diastolic blood pressure. There was no statistically significant difference in the incidence of adverse reactions, and no abnormal liver and kidney function was observed in each study. Trial sequential analysis showed that the total effective rate was cumulative across the traditional and TSA thresholds, further confirming its clinical efficacy. The evidence level was mostly low or extremely low in GRADE evaluation. The clinical application of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms is clear and safe, so it is recommended for clinical application.

Meta-analysis of efficacy and safety of Xinmailong Injection in treatment of heart failure after acute myocardial infarction / 中国中药杂志

To systematically evaluate the clinical efficacy and safety of Xinmailong Injection in the treatment of heart failure after acute myocardial infarction. Seven Chinese and English databases, namely CNKI, VIP, Wanfang, SinoMed and PubMed, EMbase, Cochrane Library, were retrieved from the establishment of the database to March 2020. Randomized controlled trials for Xinmailong Injection in the treatment of heart failure after acute myocardial infarction were screened out. Cochrane collaboration network bias risk assessment tool was used to evaluate the literature quality of the studies included, and RevMan 5.3 software was used for Meta-analysis. A total of 926 relevant literatures were retrieved, and 12 studies were finally included, involving 972 patients, including 486 patients in the treatment group and 486 patients in the control group. The quality of the literatures included was generally low. The results of Meta-analysis showed that Xinmailong Injection combined with Western medicine could decrease the levels of BNP(SMD=-5.90, 95%CI[-8.45,-3.36], P<0.000 01) and NT-proBNP(SMD=-2.28, 95%CI[-3.13,-1.43], P<0.000 01) and decrease the levels of cTnI(SMD=-2.91, 95%CI[-4.21,-1.60], P<0.000 1), increase LVEF(MD=4.67, 95%CI[4.19, 5.16], P<0.000 01), increased 6 MWT(MD=73.90, 95%CI[67.51, 80.28], P<0.000 01], decreased LVEDD(MD=-5.46, 95%CI[-9.66,-1.25], P=0.01), reduce the level of serum inflammatory factor(hs-CRP, CRP, IL-6). In terms of safety, less adverse reactions occurred in the study, with no impact on the treatment. The results showed that clinical use of Xinmailong Injection combined with Western medicine in the treatment of heart failure after acute myocardial infarction can further alleviate clinical symptoms and relevant indexes, with less adverse reactions. However, due to the limitations in quantity and quality of the clinical studies included, the positive results can only be used as a hint and reference for clinical diagnosis and treatment, and more high-quality studies are needed to further confirm its efficacy.

Systematic evaluation of efficacy and safety of Songling Xuemaikang Capsules in treatment of essential hypertension / 中国中药杂志

To evaluate the efficacy and safety of Songling Xuemaikang Capsules combined with conventional Western medicine in the treatment of essential hypertension. PubMed, VIP, CNKI, Wanfang and other databases were retrieved from the establishment of the database to February 2020 for clinical randomized controlled trial(RCT) about Songling Xuemaikang Capsules combined with conventional Western medicine in the treatment of essential hypertension. The literatures were screened out according to the inclusion criteria, and RevMan 5.3 software was used for Meta-analysis. A total of 3 100 patients in 27 RCTs were enrolled. According to Meta-analysis, Songling Xuemaikang Capsules combined with conventional Western medicine could effectively reduce systolic blood pressure(MD=-7.88,95%CI[-9.68,-6.08],P<0.000 01) and diastolic blood pressure(MD=-7.85, 95%CI[-9.07,-6.62], P<0.000 01), triglyceride(MD=-0.46, 95%CI[-0.66,-0.26], P<0.000 01) and total cholesterol(MD=-0.92, 95%CI[-1.49,-0.35], P=0.001), but increase HDL cholesterol(MD=0.51, 95%CI[0.28, 0.73], P<0.000 01), with a better effect than the Western medicine group alone. The results of LDL-C analysis showed that there was no significant difference between the two groups(MD=-0.91, 95%CI[-1.82, 0.01], P=0.05). The subgroup analysis suggested that reduced systolic blood pressure may be related to the use of ARB. There was a close correlation between CCB drugs and the decrease of diastolic blood pressure. In addition, there was no significant difference in the compliance and the incidence of adverse reactions. Clinical application of Songling Xuemaikang Capsules combined with Western medicine in the treatment of patients with essential hypertension has clear efficacy and certain safety. More clinical randomized controlled trials are needed for verification in the future.

[Systematic review of efficacy and safety of Xinmailong Injection in treatment of coronary heart disease complicated with heart failure].

To systematically evaluate the efficacy and safety of Xinmailong Injection in the treatment of coronary heart disease complicated with heart failure. Seven databases,namely CNKI, VIP,WanFang,SinoMed,PubMed,EMbase,Cochrane Library, were retrieved by computer for collecting the randomized controlled trials about Xinmailong Injection in the treatment of coronary heart disease complicated with heart failure. The literatures were screened out, data was extracted, and the methodological quality evaluation was conducted by 2 researchers independently according to inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis and corresponding description analysis. A total of 19 studies involving 1 922 patients were included, including 967 cases in the trial group and 955 cases in the control group. All the clinical studies showed a low quality. Meta-analysis results showed that Xinmailong Injection combined with conventional treatment could better reduce the BNP level(SMD=-3.34, 95%CI[-4.06,-2.63]) in patients of coronary heart disease complicated with heart failure or NT-proBNP level, improve the cardiac function(RR=1.23,95%CI[1.18,1.29]) and LVEF(MD=6.85,95%CI[4.93,8.76]),increase 6 MWT(MD=24.34, 95%CI[16.05, 32.64]) and VEGF(MD=26.39,95%CI[24.30,28.49]),and decreased LVEDD(MD=-4.06, 95%CI[-6.33,-1.80]). And subgroup analysis suggested that the course of treatment may be related to the increase of LVEF. This study found that Xinmailong Injection for coronary heart disease complicated with heart failure can further alleviate clinical symptoms and relevant indicators, with no serious adverse reaction. However, it still needs the support of well-designed multicenter, double-blind and high-quality clinical trials.

Protective effects of Jiashen Prescription () on myocardial infarction in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effects of Jiashen Prescription (, JSP) on myocardial infarction (MI) size and cardiac function at the early stage of MI in rats.</p><p><b>METHODS</b>One hundred male Sprague-Dawley rats were subjected to sham-operation or MI induced by ligating the left anterior descending coronary artery. The rats with MI were treated with vehicle, JSP 3 and 6 g/(kg·d), or losartan 10 mg/(kg·d) for 1 week.</p><p><b>RESULTS</b>Compared with the vehicle-treated MI rats, 6 g/(kg·d) JSP reduced MI size 3 days after MI (P<0.05), and attenuated the MI-induced increases in left ventricular end-diastolic and end-systolic dimension and decreases in fractional shortening and ejection fraction 1 week after MI (P<0.05). In addition, 6 g/(kg·d) JSP and losartan were equally effective in reducing MI size and enhancing cardiac functional recovery.</p><p><b>CONCLUSION</b>JSP reduces MI size and improves cardiac function after MI, suggesting that JSP has potential as a therapy for MI.</p>

Effect of clinical pathways based on integrative medicine for patients with chronic heart failure: a multi-center research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To assess a multi-center study effectiveness of clinical pathways based on integrative medicine (IM) for chronic heart failure (CHF) patients.</p><p><b>METHODS</b>A combined method of historical control study and clinical study on concurrent control was used. After the standard management for clinical pathways was carried out in four hospitals at home, the effects on hospitalization days, medical expenses, clinical efficacy, patient satisfaction, and quality of life were assessed.</p><p><b>RESULTS</b>Results of non-concurrent historical control study showed that: the hospital stay was significantly shorter in the pathways group than in the retrospective group (12.59 days vs 18.44 days), and the total cost of hospitalization was significantly reduced in the pathways group (yen 9 051.90 vs yen 11 978.40), showing statistical difference (P < 0.01). Moreover, the effect on the heart function was better in the pathways group than in the retrospective group (the markedly effective rate: 45.60% vs 21.90%; the total effective rate: 96.80% vs 86.10%), showing statistical difference (P < 0.01). Results of clinical study on concurrent control showed that the hospital stay was significantly shorter in the pathways group than in the control group (11.19 days vs 13.21 days), showing statistical difference (P < 0.05). The average total cost of hospitalization was significantly lower in the pathways group than in the control group (yen 8 656.80 vs yen 11 609.70), showing statistical difference (P < 0.01). As for clinical efficacy of Chinese medical syndrome, the total effective rate was higher in the pathways group than in the control group (97.10% vs 93.62%), showing statistical difference (P < 0.05). The markedly effective rate of heart function was better in the pathways group than in the control group, showing statistical difference (49.30% vs 38.30%, P < 0.05). The overall satisfaction was higher in the pathways group than in the conventional group (P < 0.01). There was no statistical difference in the mortality within 3 months after discharge from hospital, and the readmission rate due to heart failure between the two groups (P > 0.05). But there was statistical difference in the quality of life (P < 0.05).</p><p><b>CONCLUSION</b>The pathway could shorten the hospitalization time, decrease the cost of hospitalization, improve the clinical efficacy, improve patients' quality of life and satisfaction, therefore, it could be spread nationwide.</p>

Effects of Xinjining extract on inward rectifier potassium current in ventricular myocytes of guinea pig / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect of Xinjining extract (, XJN) on inward rectifier potassium current (I(K1)) in ventricular myocyte (VMC) of guinea pigs and its anti-arrhythmic mechanism on ion channel level.</p><p><b>METHODS</b>Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the I(k1) in VMC irrigated with XJN of different concentrations (1.25, 2.50, 5.00 g/L; six samples for each). The stable current and conductance of the inward component of I(K1) as well as the outward component of peak I(K1) and conductance of it accordingly was recorded when the test voltage was set on -110 mV.</p><p><b>RESULTS</b>The suppressive rate of XJN on the inward component of I(K1) was 9.54% + or - 5.81%, 34.82% + or - 15.03%, and 59.52% + or - 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak I(K1) was 23.94% + or - 7.45%, 52.98% + or - 19.62%, and 71.42% + or - 23.01%, respectively (all P<0.05). Moreover, different concentrations of XJN also showed effects for reducing I(K1) conductance.</p><p><b>CONCLUSION</b>XJN has inhibitory effect on I(K1) in guinea pig's VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.</p>

Thinking on the efficacy evaluation of TCM for treatment of heart failure / 中国中西医结合杂志

Through dissertating the current status and trend in efficacy evaluation of traditional and Western medicine for treatment of heart failure, aiming at the difference between TCM and Western medicine in efficacy evaluation and existent problems for diagnosis and treatment of heart failure. The authors proposed to establish a method for evaluating TCM clinical studies, a systematic method and thinking of indexes rating, depending upon the guidance of clinical methodologies of systematology, clinical epidemiology and evidence-based medicine, to make the efficacy evaluation founded upon the superiority of TCM and meeting to the international requisition, thus to facilitate the goingahead of TCM to the world.