Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β 1/Smad Pathway Regulation / 中国结合医学杂志

OBJECTIVE@#To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis.@*METHODS@#Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis.@*RESULTS@#After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor β 1 (TGF- β 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- β 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05).@*CONCLUSION@#Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β 1/Smad signaling pathway.

Cardiovascular Protective Effect of Shenmai Injection： A Review / 中国实验方剂学杂志

With the improvement of people's living standards and the increasing aging population， the incidence of cardiovascular diseases has sharply risen， making it the leading cause of death and a major "killer" for humans. The prevention and treatment of cardiovascular diseases still face severe challenges. Shenmai injection （SMI）， a Chinese medicinal preparation， is widely used in the prevention and treatment of cardiovascular diseases because of its individualized advantages in syndrome differentiation and definite efficacy. Meanwhile， its pharmacological effects and related mechanism are becoming increasingly clear. Modern research shows that SMI can exert cardioprotective effects by reducing myocardial inflammatory response， alleviating oxidative stress， inhibiting myocardial cell apoptosis， improving microcirculatory dysfunction after myocardial ischemia-reperfusion， protecting mitochondrial structure and function， inhibiting ventricular remodeling， reducing drug-induced cardiotoxicity， and possessing antiviral properties. Additionally， it can produce cardiovascular protection by relaxing blood vessels， protecting endothelial cells， and promoting angiogenesis. Furthermore， SMI can lower blood viscosity and lipid levels， thus improving blood rheology. In the future， more clinical trials and basic research are needed to clarify its therapeutic efficacy and target mechanism to further confirm the effectiveness and safety of its clinical application.

~1H-qNMR quantification of total ginsenosides in Shenmai Injection / 中国中药杂志

A content determination method based on ~1H-qNMR was developed for the determination of total ginsenosides in Shenmai Injection. The parameters were optimized with CD_3OD as the solvent, dimethyl terephthalate as the internal standard, the peak at δ 8.11 as the internal standard peak, and the peaks at δ 1.68 and δ 0.79 as quantitative peaks of total ginsenosides. The developed ~1H-qNMR-based method was validated methodologically. The results showed that the method could achieve accurate measurement of total ginsenosides in Shenmai Injection in the range of 0.167 6-3.091 1 mmol·L~(-1). The developed ~1H-qNMR-based method for total ginsenosides is simple in operation, short in analysis time, strong in specificity, independent of accompanying standard curve, and small in sample volume, which can serve as a reliable mean for the quality control of Shenmai Injection. This study is expected to provide new ideas for the development of quantification methods of total ginsenosides.

Fingerprint of Shenmai Injection based on ~1H-NMR technique / 中国中药杂志

Shenmai Injection is a Chinese medicinal injection prepared from Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix, which is widely used in clinical practice for the treatment and adjuvant therapy of cardiovascular diseases with significant pharmacological effects. Proton nuclear magnetic resonance spectroscopy(~1H-NMR) has the advantages of simple and nondestructive sample pretreatment, fast analysis, abundant chemical information, quantification and no need to follow the standard curve. It is widely used in the analysis and research of complex mixtures of traditional Chinese medicine, clinical blood and urine samples. In this study, the ~1H-NMR fingerprint of Shenmai Injection was established. Thirty-two chemical components were identified, including seven amino acids, eight small molecular organic acids, one alkaloid, four sugars, two nucleosides, seven saponins, and three other components. Pearson's correlation coefficient and multivariate analysis of variance(principal component analysis combined with hierarchical cluster analysis) were applied based on the ~1H-NMR fingerprint to evaluate the quality consistency. The results showed high-quality consistency of 82 batches of Shenmai Injection. This study confirms that the ~1H-NMR fingerprint has great potential in the application of quality control of Chinese medicinal injection.

Effect of Shenmai Injection on Long-Term Prognosis of Patients with Chronic Heart Failure: A Multicenter, Large Sample Capacity, Long-Term Follow-Up Retrospective Cohort Study / 中国结合医学杂志

OBJECTIVE@#To explore the effect of Shenmai Injection (SMI) on the long-term prognosis of patients with chronic heart failure (CHF).@*METHODS@#The Hospital Information System was used to extract data of CHF patients, and the retrospective cohort study was conducted for analysis. In non-exposed group, standardized Western medicine treatment and Chinese patent medicine or decoction were applied without combination of SMI while in the exposed group, SMI were applied for more than 7 days. Evaluation indicators are followed with New York Heart Association functional classification (NYHA classification), left ventricular ejection fraction (LVEF), N-terminal brain natriuretic peptide precursor (NT-ProBNP), cardiogenic death and heart failure (HF) readmission. Statistical analysis includes Kaplan-Meier analysis and Cox regression which are used to explore the relationship between SMI and outcome events.@*RESULTS@#A total of 1,211 eligible CHF patients were involved and finally 1,047 patients were followed up successfully. After treatment, the cases of NYHA classification decline in the exposed and non-exposed groups accounted for 64.30% and 43.45%, respectively; the improvement values of LVEF were 8.89% and 7.91%, respectively; the improvement values of NT-ProBNP were 909 pg/mL and 735 pg/mL, respectively. After exposure on SMI, the rates of cardiogenic death and HF readmission reduced from 15.43% to 10.18% and 38.93% to 32.37%. According to Kaplan-Meier analysis, the log-rank P value of SMI and cardiogenic death was 0.014, while the counterpart of SMI and HF readmission was 0.025. Cox regression analysis indicated that for cardiogenic death, age, cardiomyopathy, diabetes, and NYHA classification were risk factors while β-blockers, aldosterone receptor antagonists, Chinese patent medicine/decoction and SMI were protective factors. Likewise, for HF readmission, age, cardiomyopathy, and NYHA classification were risk factors while SMI was a protective factor.@*CONCLUSION@#Combination with SMI on the standardized Western medicine treatment can effectively reduce cardiogenic mortality and readmission rate in CHF patients, and thereby improve the long-term prognosis.

Network meta-analysis of efficacy of Chinese medicine injection in treatment of heart failure after acute myocardial infarction / 中国医师杂志

Objective:This study aimed to systematically evaluate the efficacy of Chinese medicine injection (CMI) in the treatment of heart failure (HF) after acute myocardial infarction (AMI).Methods:China National Knowledge Infrastructure (CNKI), WanFang Data, VIP, The Cochrane Library, PubMed, and EMbase databases were electronically searched from inception to October 2021 to identify randomized controlled trials (RCTs) on CMI for treating HF after AMI. Two reviewers independently screened literature, extracted data, and evaluated the bias risk of included studies. Network meta-analysis was then performed by ADDIS1.16.6 software and Stata 16.0 software.Results:A total of 55 studies were included involving 4 760 patients with HF after AMI and 3 types of CMIs, including Shenmai, Shenfu, Xinmailong injections. The results of network meta-analysis showed that Xinmailong injection was superior to Shenmai injection and Shenfu injection in improving the total effective rate and reducing left ventricular end diastolic diameter (LVEDD); Shenmai injection was superior to Xinmailong injection and Shenfu injection in reducing B-type natriuretic peptide (BNP); Shenfu injection was superior to Shenmai injection and Xinmailong injection in increasing left ventricular ejection fraction (LVEF) and reducing heart rate (HR).Conclusions:The combined 3 types of CMIs for treating HF after AMI can improve the clinical efficacy when compared with conventional Western medicine treatment. Among them, Xinmailong injection is better in improving the total effective rate and reducing LVEDD, Shenmai injection is more advantageous in reducing BNP, and Shenfu injection has the best efficacy in improving LVEF and reducing HR.

Active components and action mechanism of Shenmai Injection in treatment of atrial fibrillation based on network pharmacology and molecular docking / 中国中药杂志

This study aims to explore the active components and molecular mechanism of Shenmai Injection in the treatment of atrial fibrillation(AF) based on the application of network pharmacology and molecular docking technology. The chemical components of single herbs of Shenmai Injection were collected from TCMSP and TCMID, with the standard chemical name and PubChem CID(referred to as CID) obtained from PubChem database. The active components were screened using SwissADME, and their targets were predicted using SwissTargetPrediction. Targets related to AF treatment were identified using GeneCards, OMIM, and other databases. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. The single herb-active component-potential target network was constructed using Cytoscape, and the clusterProfiler R function package was used to perform the gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment. The protein-protein interaction(PPI) network of intersection targets was generated based on the STRING database. The hub target protein was identified by visualization using Cytoscape, and then docked to its reverse-selected active components. The analysis showed that there were 65 active components with 681 corresponding targets in Shenmai Injection, 2 798 targets related to AF treatment, and 235 intersection targets involving 2 549 GO functions and 153 KEGG pathways. Finally, hub target proteins, including RAC-alpha serine/threonine-protein kinase(AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA), and estrogen receptor 1(ESR1), were screened out by PPI network visualization. The molecular docking was performed for 39 active components screened out in reverse, among which 30 active components de-monstrated high affinity. Among them, homoisoflavanoids CID 10871974, CID 5319742, and CID 10361149 had stronger affinity docking with AKT1. This study preliminarily indicates that Shenmai Injection treats AF through multiple components, multiple targets, and multiple pathways. Homoisoflavonoids of Ophiopogon japonicus are its important active components, which target AKT1 to regulate metabolism, inflammation, and apoptosis in AF treatment.

Overview of systematic reviews on Shenmai Injection in prevention and treatment of diseases / 中国中药杂志

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.

Analysis of chemical constituents in Shenmai Injection by LC-Q-TOF-MS and LC-IT-MS / 中国中药杂志

The chemical constituents in Shenmai Injection(SMI) were qualitatively analyzed by using liquid chromatography/quadrupole time-of-flight mass spectrometry(LC-Q-TOF-MS) and liquid chromatography-ion trap-mass spectrometry(LC-IT-MS). The analysis was performed on an Agilent Zorbax SB-C_(18)(4.6 mm×250 mm, 5 μm) and gradient elution was carried out with 0.05% formic acid solution-acetonitrile as mobile phase at a flow rate of 0.6 mL·min~(-1) and a column temperature of 30 ℃. Mass spectrometry data of the components in SMI were collected in negative ion mode. The structures of components were speculated and identified by analyzing mass spectrometry data, comparing with standards, and referring to related literature. A total of 64 components in SMI were estimated, and the structures were confirmed in 16 of them by comparison with standards. Fifty-six compounds derived from Ginseng Radix et Rhizoma Rubra included 34 protopanaxadiol ginsenosides, 19 protopanaxatriol ginsenosides, 1 oleanane ginsenosides and 2 other glycosides. Eight compounds derived from Ophiopogonis Radix included 7 steroidal saponins, and 1 monoterpene glycoside. The results of this study would provide an important theoretical basis for the improvement of the quality control standards and the discovery of effective constituents in SMI.

Multi-index optimization of alcohol extraction and water precipitation processes of Shenmai Injection based on quality by design concept / 中草药

Objective: The alcohol extraction and water precipitation processes of Shenmai Injection were optimized based on quality by design (QbD) concept and satisfaction algorithm. Methods: Hazard and operational analysis method was applied to conduct risk assessment of various process parameters in alcohol extraction and water precipitation processes of Shenmai Injection. Ethanol concentration, extraction time and alcohol-material ratio were selected as the critical process parameters of alcohol extraction, and the material pH, temperature and time were selected as the critical process parameters of water precipitation. A multiple linear regression model of critical process parameters and critical quality attributes were established by using Box-Behnken design. A design space was delineated according to the level of each index. Finally, the optimum operating condition was determined by the multi-index optimization algorithm. Results: Within the scope of the design space, when the alcohol concentration was 89.0%, the extraction time was 110 min, the alcohol-material ratio was 2.99, the desirability function of alcohol extraction of 0.722 was the best. When the material pH was about 4, the time was 40 h, the temperature was 2.0 ℃, the desirability function of water precipitation of 0.995 was the best. When the material pH was about 5, the time was 35 h, the temperature was 2.0 ℃, the desirability function of water precipitation of 0.999 was the best. Conclusion: The optimal conditions were determined based on QbD and satisfaction algorithm were conducive to ensuring the product quality and reducing the cost of production. This study has reference value for the guidance of pharmaceutical process research and actual industrial production.

Effects of Baihe Gujin Decoction Combined with Shenmai Injection on Therapeutic Efficacy and Related Indexes in Elderly Patients with Ventilator-associated Pneumonia / 中国药房

OBJECTIVE：To investigate t he effects of Baihe gujin decoction combined with Shenmai injection on therapeutic efficacy and related indexes in elderly patients with ventilator-associated pneumonia. METHODS ：A total of 75 elderly patients with ventilator-associated pneumonia who were admitted to the Intensive Care Unit （ICU）of Zhuji Hospital of TCM from Apr. 2018 to Oct. 2019 were included. They were randomly divided into control group ，Shenmai group ，Baihe gujin decoction+Shenmai group ， with 25 cases in each group. Control group was given conventional treatments as Piperacillin sodium tazobactam sodium injection 4.5 g，ivgtt，q8 h for anti-infective treatment+ Ambroxol hydrochloride injection 4 mL，iv，bid for expectorant+ Doxofylline injection 20 mL，qd for relieving spasm and asthma+maintaining water ，electrolyte and acid-base balance. Shenmai group was given Shenmai injection 100 mL，ivgtt，qd，on the basis of control group. Baihe gujin decoction+Shenmai group was given Baihe A101） gujin decoction 200 mL nasally ， morning and evening ，on m the basis of Shenmai group. Each group took 7 days as a course of treatment ，and the treatment was continued for 2 courses. Acute physiology and chronic health status （APACHE）Ⅱ score，C-reactive protein （CRP）in peripheral blood ，procalcitonin（PCT），bronchial CD 68 count were observed in 3 groups before and after treatment while the mechanical ventilation time ，hospitalization time in the ICU and ADR recorded. RESULTS：Before treatment ，there was no statistically significant difference in APACHE Ⅱ score，the levels of CRP and PCT ， bronchial CD 68 count among 3 groups（P＞0.05）. After 14 days of treatment ，APACHE Ⅱ score，CRP and PCT levels of all 3 groups were significantly lower than before treatment ；bronchial CD 68 count was significantly higher before treatment ，the order of bronchial CD 68 cell count was Baihe gujin decoction+Shenmai group ＞Shenmai group ＞control group （P＜0.05 or P＜0.01）；after 7 days of treatment ，the order of CRP and PCT levels was Baihe gujin decoction+Shenmai group ＜Shenmai group ＜control group （P＜0.05）；after 14 days of treatment ，there was no staistically significant difference in APACHE Ⅱ score，CRP and PCT levels among 3 groups（P＞0.05）. After treatment ，the order of mechanical ventilation time and ICU hospitalization time was Baihe gujin decoction + Shenmai group ＜Shenmai group ＜control group （P＜0.05 or P＜0.01）. There was no significant difference in the incidence of ADR among 3 groups（P＞0.05）. CONCLUSIONS ：Based on routine treatment ，Baihe gujin decoction combined with Shenmai injection can improve the immune function of lung macrophages in the elderly patients with ventilator-associated pneumonia，inhibite pulmonary inflammation progress ，reduce mechanical ventilation time ，shorten the length of hospital stay with good safety.

Effects of Shenmai injection combined with enteral nutrition on immune function of patients with severe cardiac insufficiency / 中国中西医结合急救杂志

Objective To observe the effect of Shenmai injection combined with enteral nutrition (EN) on immune function in patients with severe cardiac insufficiency. Methods Fifty-seven patients with severe cardiac insufficiency admitted to the Department of Critical Care Medicine of Taizhou Hospital of Zhejiang Province from June 2015 to June 2018 were divided into an EN group (31 cases) and an EN group combined with Shenmai injection group (26 cases). The EN group was given EN on the basis of routine western medicine treatment, while in the EN combined with Shenmai injection group was treated additionally by intravenous drip of Shenmai injection 100 mL/d on the basis of above EN group treatment. The efficacies of the two groups were evaluated after consecutive 7-day treatment in the two groups. The changes in levels of subsets of T-lymphocytes (CD3+, CD4+, CD8+, CD4+/CD8+) and immunosuppressive cells CD14+ monocyte human leukocyte antigen DR (HLA-DR) were observed before and after treatment. Results After treatment, the levels of T-cell subsets CD3+, CD4+, CD4+/CD8+ and CD14+ monocytes HLA-DR in the peripheral blood of the two groups were significantly higher than those before treatment [CD3+: EN group was 0.539±0.126 vs. 0.379±0.093,Shenmai injection group was 0.652±0.185 vs. 0.393±0.091; CD4+: EN group was 0.402±0.121 vs. 0.275±0.066,Shenmai injection group was 0.524±0.168 vs. 0.281±0.077; CD4+/CD8+:EN group was 1.83±0.70 vs. 1.11±0.70,Shenmai injection group was 2.81±0.91 vs. 1.19±0.58; CD14+HLA-DR:EN group was (43.3±7.1)% vs. (35.4±5.7)%,Shenmai injection group was (54.9±6.2)% vs. (36.1±8.3)%]; After treatment, CD8+ in EN group decreased (0.223±0.052 vs. 0.253±0.081), while CD8+ in shenmai injection group increased (0.288±0.051 vs. 0.259±0.078), and the increase degrees of the above-mentioned indexes in EN combined with Shenmai injection group were more obvious than those in the EN group after treatment [CD3+: 0.652±0.185 vs. 0.539±0.126, CD4+: 0.524±0.168 vs. 0.402±0.121, CD8+: 0.288±0.051 vs. 0.223±0.052, CD4+/CD8+: 2.81±0.91 vs. 1.83±0.70, CD14+HLA-DR: (54.9±6.2)%, (43.3±7.1)%, all P < 0.05]. Conclusion The combined use of Shenmai injection and early EN can improve the immune function of T-lymphocytes in patients with severe cardiac insufficiency. The mechanism may be related to the enhancement of the activation of T lymphocytes and promotion of the CD14+ monocytes increase and immune function.

Effect of of Shenmai injection on hemodynamics and serum inflammatory factors in patients with septic shock / 中国中西医结合急救杂志

Objective To observe the effect of Shenmai injection on hemodynamics and serum inflammatory factors in patients with septic shock. Methods One hundred and fifty patients with septic shock admitted to Tianjin Fourth Center Hospital from August 2015 to March 2017 were enrolled and they were divided into a western medicine routine treatment group and an integrated traditional Chinese and western medicine treatment group according to the random number table method, 75 patients in each group. Both groups were given symptomatic treatment of basic western medicine, and the integrated traditional Chinese and western medicine treatment group was additionally given intravenous infusion (IV) of 30 mL Shenmai injection on the basis of conventional treatment, both groups were treated for consecutive 14 days. The changes in hemodynamic parameters, serum inflammatory factors: tumor necrosis factor-α (TNF-α) and interleukin (IL-6, IL-1β) were observed before and after treatment in the two groups, and the clinical efficacies of the two groups were evaluated 14 days after treatment. Results After treatment in both groups, hemodynamic indexes were improved, heart rate (HR) was decreased, and mean arterial pressure (MAP), central venous pressure (CVP), cardiac output index (CI) and peripheral vascular resistance index (SVRI) were increased; after 14 days of treatment, HR in the integrated traditional Chinese and western medicine treatment group was significantly lower than that in the western medicine routine treatment group (bpm: 101.8±3.1 vs. 104.9±9.3), while MAP [mmHg (1 mmHg = 0.133 kPa): 71.2±4.3 vs. 67.3±3.5], CI (mL·s-1·m-2: 3.6±0.4 vs. 3.4±0.6) and SVRI (kPa·s·L-1·m-2:190.37±24.91 vs. 180.23±20.13) were significantly higher than those in the western medicine routine treatment group (all P < 0.05). TNF-α, IL-6 and IL-1β were decreased in both groups after treatment; after 14 days of treatment, the above indexes in the integrated traditional Chinese and western medicine treatment group were significantly lower than those in the western medicine routine treatment group [TNF-α (ng/L): 226.3±42.8 vs. 273.7±29.4, IL-6 (ng/L):223.7±31.2 vs. 259.3±51.3, and IL-1β (ng/L): 95.1±20.7 vs. 132.4±47.5]. The total clinical effective rate in the integrated traditional Chinese and western medicine treatment group was significantly higher than that in the western medicine routine treatment group [93.3% (70/75) vs. 54.7% (41/75), P < 0.05]. Conclusion Shenmai injection can improve hemodynamics and regulate inflammatory factors; the therapeutic effect for treatment of septic shock is significant.

Clinical Observation of Cefoperazone Sodium and Sulbactam Sodium Combined with Shenmai Injection in the Treatment of Elderly Stroke Associated Pneumonia / 中国药房

OBJECTIVE:To observe therapeutic efficacy and safety of cefoperazone sodium and sulbactam sodium combined with Shenmai injection in the treatment of elderly stroke associated pneumonia(SAP). METHODS:A total of 84 SAP patients in Dazhou Municipal Central Hospital during Mar. 2016-Mar. 2017 were divided into control group(42 cases)and observation group (42 cases)according to random number table. Based on routine treatment,control group was additionally given Cefoperazone sodium and sulbactam sodium for injection 3 g added into 5% Glucose injection 100 mL,intravenously,twice a day;suitable antibiotics were selected according to the results of pathogenic examination and drug sensitivity test. Observation group was additionally given Shenmai injection 100 mL added into 5% Glucose injection 250 mL intravenously,once a day,on the basis of control group. Both groups were treated for consecutive 2 weeks. Clinical efficacies of 2 groups were observed,and the levels of T-lymphocyte subsets(CD4+,CD8+,CD4+/CD8+)and inflammatory markers(TNF-α,hs-CRP,PCT),length of hospital stay before and after treatment. The ADR was recorded. RESULTS:The total response rate(95.24%)and marked response rate (47.62%)of observation group were significantly higher than those of control group(83.33%,23.81%);length of hospital stay in observation group [(15.24±3.53)d] was significantly shorter than control group [(18.43±4.21)d],with statistical significance (P<0.05).After treatment,the levels of CD4+and CD4+/CD8+in 2 groups were significantly higher than before treatment,and the observation group was significantly higher than the control group;the levels of CD8 +,TNF-α,hs-CRP and PCT in 2 groups were significantly lower than before treatment;the observation group was significantly lower than the control group,with statistical significance(P<0.05);there was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Based on routine treatment,cefoperazone sodium and sulbactam sodium combined with Shenmai injection treat SAP significantly,can effectively improve immune function, reduce inflammation level and shorten the length of hospital stay without increasing the occurrence of ADR.

Systematic Evaluation of Shenmai Injection for Prevention and Treatment of Cardiotoxicity Induced by Chemotherapy of Malignant Tumor / 中国中医药信息杂志

Objective To systematically evaluate the clinical efficacy of Shenmai Injection for the prevention and treatment of cardiotoxicity induced by chemotherapy of malignant tumor. Methods Literature about RCTs of Shenmai Injection for the prevention and treatment of cardiotoxicity induced by chemotherapy of malignant tumor in CNKI, Wanfang Database, CBM, VIP, Pub Med, Cochrane Library, Embase, and Web of Science was retrieved by computer from the establishment of database to March 2017. Two investigators independently conducted literature screening, data extraction, and literature quality evaluation. Rev Man 5.3 software was used for Meta-analysis. Results 14 articles were included in the study, involving 1105 patients. The results of Meta-analysis showed that the incidence of abnormal electrocardiogram in Shenmai Injection group was significantly lower than that in control group [RR=0.36, 95％CI (0.29, 0.44), P＜0.000 01]. CK-MB elevation value [SMD=-0.29, 95％CI (-0.58, 0.00), P=0.05]and c Tn T elevation value [SMD=-1.28, 95％CI (-2.48, -0.09), P=0.04]in Shenmai Injection group were less than control group, with statistical significance. Conclusion Shenmai Injection is beneficial to the prevention and treatment of early acute cardiac toxicity and myocardial injury induced by chemotherapy of malignant tumor. However, more large-scale, multi-center, and high-quality clinical RCTs are needed for further verification

Efficacy of Shenmai injection on the myocardial ischemia-reperfusion injury in patients underwent thoracoscopic cardiac surgery / 中国内镜杂志

Objective To study the protective effect of Shenmai injection on myocardial ischemia reperfusion injury in patients underwent thoracoscopic cardiac surgery during cardiopulmonary bypass (CPB). Methods 18 patients with congenital heart disease with CPB thoracoscopic cardiac surgery were randomly divided into two groups (9 cases in each group): controlled group and experimental group. The controlled group did not give any intervened drugs, and the experimental group gave the injection of Shenmai that were added into heart cold cardioplegia (2 ml/kg). The levels of the following indexes in the serum were respectively measured just after the time of induction of anesthesia (T1) and heart resuscitation (T2): Troponin T (cTnT), Creatine kinase isoenzyme (CK-MB) quality, myoglobin (Mb). And at the same time, the left ventricular ejection fraction (EF) was measured. Results The concentrations of cTnT, CK-MB and mb in the serum of both groups just after the time of heart resuscitation (T2) were significantly increased more than just after the time of induction of anesthesia (T1) (P < 0.05). But the concentrations of cTnT, CK-MB and Mb in the experimental group were significantly lower than that in the controlled group just after the time of cardiac resuscitation. And EF was significantly higher than the controlled group (P < 0.05). Conclusion Shenmai injection can protect the myocardium from ischemia-reperfusion injury in patients underwent thoracoscopic cardiac surgery during cardiopulmonary bypass (CPB).

Pharmacokinetics of Shengmai Injection and Shenmai Injection in Angina Pectoris Patients / 世界科学技术-中医药现代化

This study was aimed to compare the pharmacokinetics (PK) of Shengmai injection and Shenmai injection with a single injection administration using a constant speed in subjects with stable angina pectoris.A total of 20 subjects with stable angina pectoris were divided into two groups.Each group was administered with Shengmai and Shenmai injection.The liquid chromatography-mass spectrometry (LC/MS) was adopted to determine concentrations of ginsenosides in plasma at different time points.PK parameters were calculated for comparison.The results showed that after a single intravenous infusion of Shengmai and Shenmai injection,the Cm.of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in Shenmai group were higher than those of the Shengmai group with statistical significance (P ≤0.05).There were differences on the T1/2 of ginsenoside Rg1,AUC0-144h and CL of ginsenoside Rc,as well as Tmax of ginsenoside Rd (P ≤ 0.05).However,there was no significant difference shown on other PK parameters.It was concluded that after a single Shengmai or Shenmai injection,there were PK differences of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and ginsenoside Rc in the human body.The clinical medication selection should be based on syndrome differentiation and treatment of patients.

Effect of Shenmai injection on cytokines and ESAT-6/CFP-10 levels in patients with COPD with pulmonary tuberculosis / 中国生化药物杂志

Objective To investigate the effect of Shenmai injection on cytokines and ESAT-6/CFP-10 levels in patients with Chronic obstructive pulmonary disease(COPD)with pulmonary tuberculosis.Methods158 patients with COPD with pulmonary tuberculosis from the Department of Respiratory in our hospital were selected and divided into 2 groups, 79 cases in the control group treated with routine treatment, 79 cases in the experiment group treated with Shenmai injection on the basis of the control group, levels of neurotransmitters in the brain, serum ESAT-6 protein, CFP-10 protein, IFN-γ levels, cytokine levels, peripheral blood immune cell levels, and the clinical effect and the focus absorption efficiency were compared after the treatment.ResultsThe clinical total effective rate in the control group(84.81%)was lower than that in the experiment group(94.94%), with significant difference (P<0.05);the focus absorption efficiency in the control group(87.33%)was lower than that in the experiment group(96.21%), with significant difference (P<0.05);compared with the control group, serum ESAT-6 protein、 CFP-10 protein、IFN-γ levels were lower after treatment in the experiment group, the serum levels of TNF-α、IL-6、sIL-2R were lower, peripheral blood levels of NK cells, CD4+T lymphocytes and CD4+/CD8+ were higher, peripheral blood level of CD8+T lymphocytes was lower, with significant difference (P<0.05).ConclusionShenmai injection can significantly reduce the serum levels of TNF-α、IL-6、sIL-2R and ESAT-6/CFP-10 in patients with COPD with pulmonary tuberculosis, improve cellular immune function, promote the absorption of lesions effectively,and improve clinical efficacy.

Efficacy and Safety of Shenmai Injection in Adjuvant Therapy of Angina Pectoris:A Systematic Review / 中国药房

OBJECTIVE:To evaluate the therapeutic efficacy and safety of Shenmai injection in adjuvant therapy of angina pectoris,and to provide evidence-based reference in clinic.METHODS:Retrieved from CJFD,Wanfang database,VIP and PubMed,randomized control trials (RCTs) about Shenmai injection combined with routine plan (trial group) vs.routine plan sole (control group) in the treatment of angina pectoris were collected.Meta-analysis was conducted by using Rev Man 5.3 statistical software after data extraction and quality evaluation with Cochrane systematic evaluator manual 5.1.0.RESULTS:A total of 25 studies were included,involving 2 093 patients.Meta-analysis showed that clinical efficacy rate [RR=I.31,95％ CI(1.25,1.37),P＜0.001] and ECG total response rate [RR=1.42,95％CI(1.31,1.54),P＜0.001] of trial group were significantly higher than those of control group,with statistical significance.Results of subgroup analysis showed that among high-dose subgroup(＞40 mL/d) and low-dose subgroup(≤40 mL/d),clinical efficacy rate [high dose:RR=1.26,95％ CI (1.19,1.34),P＜0.001;low dose:RR=1.36,95％ CI (1.27,1.45),P＜0.001] and ECG total response rate [high dose:RR=1.39,95％CI(1.22,1.60),P＜0.001;low dose:RR=1.43,95％ CI (1.30,1.58),P＜0.001] of trial group were significantly higher than those of control group,with statistical significance.There was no statistical significance in the incidence of ADR between 2 groups [RR=0.66,95％CI(0.32,1.40),P=0.28].CONCLUSIONS:Shenmai injection in adjuvant therapy of angina pectoris shows good therapeutic efficacy and safety in the treatment of angina pectoris.It is suggested to its clinical application start from the low dose.

Analysis of the rational use of Shenmai injection of 400 cases / 中国生化药物杂志

Objective To analyse the clinical usage of Shenmai injection, promote the rational use of Shenmai injection. Methods 400 hospital medical records that used Shenmai injection in 2015 were collected and reviewed from hospital information system (HIS) by retrospective analysis method, aggregated and evaluated data by EXCEL. Results In 400 cases, 11 clinical departments used the Shenmai injection, mainly in cardiology of 347 cases(86.75%).The percentage of the non-standard clinical application of Shenmai injection was 84 cases (21.00%). The non-standardized rates of solvent dispensing was 287 cases (71.75%), and the specification incompatibility accounted for 105 cases (26.25%). There was no adverse drug reaction of Shenmai injection. Conclusion The clinical use of Shenmai injection is not yet standardized, which suggests that drugs should be strictly used in accordance with the instruction, in order to avoid risks of off-label use.