Evaluation of age-adjusted Charlson comorbidity index on prognosis and application timing of Shenfu injection in elderly patients with septic shock / 中华急诊医学杂志

Objective:To evaluate the value of age-adjusted Charlson comorbidity index (aCCI) in the clinical prognosis of sepsis and septic shock in the elderly, and to further explore the role of aCCI in evaluating the timing of Shenfu injection in elderly patients with septic shock.Methods:Clinical data of elderly patients with sepsis and septic shock in Dongzhimen Hospital of Beijing University of Chinese Medicine from January 1, 2019 to January 1, 2022 were retrospectively analyzed. With the median aCCI score of all samples as the cutoff value, the patients were divided into the low aCCI score group and high aCCI score group. The prognosis of elderly patients with septic shock and the application timing of Shenfu injection with aCCI score and sequential organ failure assessment (SOFA) were compared.Results:A total of 61 patients were included, including 31 patients in the high aCCI score group. The proportion of septic shock in elderly sepsis patients was lower in the low aCCI score group ( P < 0.05). The aCCI score (95% CI: 1.229-2.615; P< 0.01) was more valuable than SOFA score (95% CI: 1.035-1.607; P< 0.05) in predicting septic shock in elderly patients with sepsis. The 28-day survival rate in the low aCCI score group was higher than that in the high aCCI score group ( P < 0.05). Both the SOFA score (95% CI: 1.010-1.364) and the aCCI score (95% CI: 1.072-10.501) were independent factors affecting the 28-day survival rate. The use of Shenfu injection was associated with 28-day survival outcome in elderly patients with septic shock (95% CI: 0.012-0.788; P < 0.05). Conclusions:aCCI score is more effective than SOFA score in assessing the risk of shock in elderly patients with septic shock, and has a certain predictive value for the survival and prognosis of elderly patients with sepsis. Shenfu injection may be beneficial to the survival and prognosis of elderly patients with septic shock, but it needs to be further verified by large-scale prospective studies.

Therapeutic Effects of Shenfu Injection in Shock / 中国结合医学杂志

Shock is the clinical manifestation of acute circulatory failure, which results in inadequate utilization of cellular oxygen. It is a common condition with high mortality rates in intensive care units. The intravenous administration of Shenfu Injection (SFI) may attenuate inflammation, regulate hemodynamics and oxygen metabolism; inhibit ischemia-reperfusion responses; and have adaptogenic and antiapoptotic effects. In this review, we have discussed the clinical applications and antishock pharmacological effects of SFI. Further in-depth and large-scale multicenter clinical studies are warranted to determine the therapeutic effects of SFI on shock.

Efficacy and safety of Shenfu injection combined with chemical medicine in the treatment of coronary heart disease combined with heart failure：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of Shenfu injection combined with chemical medicine in the treatment of coronary heart disease combined with heart failure. METHODS Retrieved from CNKI， CBM， VIP， Wanfang， PubMed， Embase and the Cochrane Library， randomized controlled trials （RCTs） about Shenfu injection combined with chemical medicine （trial group） versus chemical medicine （control group） in the treatment of heart failure with coronary heart disease were collected during the inception to August 2022. After literature screening and data extraction， the qualities of included literature were evaluated and rated by using Cochrane manual and GRADE system. Meta-analysis and Egger’s were performed with RevMan 5.3 software， and TSA 0.9.5.10 Beta software was used for trial sequential analysis. RESULTS Seventeen studies were included， with a total sample of 1 355 patients. The quality grade evidence of GRADE was all low. Meta-analysis showed that cardiac function efficacy [RR＝1.23， 95%CI （1.16，1.30）， P＜0.000 01]， the decrease of brain natriuretic peptide [MD＝－96.06， 95%CI （－116.47， －75.64）， P＜0.000 01] and the increase of left ventricular ejection fraction [MD＝5.32， 95%CI （4.03，6.60）， P＜0.000 01] in trial group were significantly better than control group； there was no statistical significance in the incidence of ADR between 2 groups [RR＝0.52，95%CI（0.22，1.22），P＝0.13]. The results of sequential analysis showed that the sample size included in this study met the requirements of meta-analysis； the results of Egger’s test showed that the results were robust and publication bias had no significant effect on the results. CONCLUSIONS Shenfu injection combined with chemical medicine in the treatment of coronary heart disease combined with heart failure can further improve the clinical symptoms and related indicators， and no serious adverse reaction is observed.

Effect of Reduning Injection， Shenfu Injection Combined with Gefitinib on Proliferation， Stemness Characteristics and Metabolism of Non-small Cell Lung Cancer Cells / 中国实验方剂学杂志

ObjectiveTo compare and observe the effect of Reduning injection （mainly clearing heat）， Shenfu injection （mainly warming Yang） combined with gefitinib on the proliferation， apoptosis， stemness characteristics and metabolism of lung cancer cells. MethodDifferent non-small cell lung cancer （NSCLC） cell lines were selected and intervened with gefitinib （5， 10， 20 μmol·L-1）， Reduning injection （0.6%， 0.9%）， Shenfu injection （0.6%， 0.9%）， gefitinib combined with Reduning injection， and gefitinib combined with Shenfu injection. Cell proliferation in each group was detected by cell counting kit-8 （CCK-8） assay， and cell apoptosis was detected by flow cytometry. The mRNA and protein expressions of lung cancer stem cell markers sex determining region Y-box 2 （Sox2） and aldehyde dehydrogenase family 1 member A1 （ALDH1A1） were determind by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The redox ratio of lung cancer cells was observed by femtosecond label-free imaging （FLI） and energy metabolism instrument was used to determine the glycolysis level in cells. ResultCompared with the blank group， Reduning injection reduced the survival rate of lung cancer cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， and up-regulated the redox ratio of cells （P<0.05）， while Shenfu injection exerted no remarkable effect on the above indexes. In addition， compared with gefitinib alone， Reduning injection combined with gefitinib inhibited the survival rate of lung cancer cells （P<0.05）， promoted the cell apoptosis （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， up-regulated the redox ratio of cells （P<0.05）， and lowered the proton efflux rate of glycolysis （P<0.05）， while Shenfu injection combined with gefitinib failed to affect these indexes of lung cancer cells significantly. ConclusionReduning injection may inhibit stemness characteristics of tumor cells by regulating their metabolism to enhance the proliferation-inhibiting and pro-apoptotic effects of gefitinib on lung cancer cells， while Shenfu injection had no significant enhancing effect on gefitinib. This indicates that epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） should be used in combination with heat-clearing Chinese medicines.

Shenfu Injection alleviates sepsis-associated lung injury by regulating HIF-1α / 中国中药杂志

Shenfu Injection(SFI) is praised for the high efficacy in the treatment of septic shock. However, the precise role of SFI in the treatment of sepsis-associated lung injury is not fully understood. This study investigated the protective effect of SFI on sepsis-associated lung injury by a clinical trial and an animal experiment focusing on the hypoxia-inducing factor-1α(HIF-1α)-mediated mitochondrial autophagy. For the clinical trial, 70 patients with sepsis-associated lung injury treated in the emergency intensive care unit of the First Affiliated Hospital of Zhengzhou University were included. The levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α were measured on days 1 and 5 for every patient. Real-time quantitative polymerase chain reaction(RT-qPCR) was performed to determine the mRNA level of hypoxia inducible factor-1α(HIF-1α) in the peripheral blood mononuclear cells(PBMCs). For the animal experiment, 32 SPF-grade male C57BL/6J mice(5-6 weeks old) were randomized into 4 groups: sham group(n=6), SFI+sham group(n=10), SFI+cecal ligation and puncture(CLP) group(n=10), and CLP group(n=6). The body weight, body temperature, wet/dry weight(W/D) ratio of the lung tissue, and the pathological injury score of the lung tissue were recorded for each mouse. RT-qPCR and Western blot were conducted to determine the expression of HIF-1α, mitochondrial DNA(mt-DNA), and autophagy-related proteins in the lung tissue. The results of the clinical trial revealed that the SFI group had lowered levels of inflammatory markers in the blood and alveolar lavage fluid and elevated level of HIF-1α in the PBMCs. The mice in the SFI group showed recovered body temperature and body weight. lowered TNF-α level in the serum, and decreased W/D ratio of the lung tissue. SFI reduced the inflammatory exudation and improved the alveolar integrity in the lung tissue. Moreover, SFI down-regulated the mtDNA expression and up-regulated the protein levels of mitochondrial transcription factor A(mt-TFA), cytochrome c oxidase Ⅳ(COXⅣ), HIF-1α, and autophagy-related proteins in the lung tissue of the model mice. The findings confirmed that SFI could promote mitophagy to improve mitochondrial function by regulating the expression of HIF-1α.

Shenfu Injection improves chronic heart failure by regulating pyroptosis based on NLRP3/caspase-1 pathway / 中国中药杂志

This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1β, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1β, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1β and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.

Protective effect of Shenfu Injection on regulation of autophagy in rats with chronic heart failure based on PI3K/Akt/mTOR pathway / 中国中药杂志

This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.

Pathogenesis of chronic heart failure in rats based on ferroptosis-mediated oxidative stress and intervention effect of Shenfu Injection / 中国中药杂志

This study aims to investigate the pathogenesis of chronic heart failure based on ferroptosis-mediated oxidative stress and predict the targets of Shenfu Injection in treating chronic heart failure. A rat model of chronic heart failure was established by the isoproterenol induction method. According to the random number table method, the modeled rats were assigned into three groups: a model group, a Shenfu Injection group, and a ferrostatin-1(ferroptosis inhibitor) group. In addition, a normal group was designed. After 15 days of intervention, the cardiac mass index and left ventricular mass index were determined. Echocardiography was employed to eva-luate the cardiac function. Hematoxylin-eosin staining and Masson staining were employed to reveal the pathological changes and fibrosis of the heart, and Prussian blue staining to detect the aggregation of iron ions in the myocardial tissue. Transmission electron microscopy was employed to observe the mitochondrion ultrastructure in the myocardial tissue. Colorimetry was adopted to measure the levels of iron metabolism, lipid peroxidation, and antioxidant indicators. Flow cytometry was employed to measure the content of lipid-reactive oxygen species(ROS) and the fluorescence intensity of ROS. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of ferroptosis-related factors in the myocardial tissue. The results showed that the rats in the model group had reduced cardiac function, elevated levels of total iron and Fe~(2+), lowered level of glutathione(GSH), increased malondialdehyde(MDA), decreased superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px), and rising levels of ROS and lipid-ROS. In addition, the model group showed fibrous tissue hyperplasia with inflammatory cell infiltration and myocardial fibrosis, iron ion aggregation, and characteristic mitochondrial changes specific for iron death. Moreover, the model group showcased upregulated protein and mRNA levels of p53 and COX2 and downregulated protein and mRNA levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. The intervention with Shenfu Injection significantly improved the cardiac function, recovered the iron metabolism, lipid peroxidation, and antioxidant indicators, decreased iron deposition, improved mitochondrial structure and function, and alleviated inflammatory cell infiltration and fibrosis. Furthermore, Shenfu Injection downregulated the mRNA and protein levels of p53 and COX2 and upregulated the mRNA and protein levels of GPX4, FTH1, SLC7A11, and Nrf2 in the myocardial tissue. Shenfu Injection can improve the cardiac function by regulating iron metabolism, inhibiting ferroptosis, and reducing oxidative stress injury.

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.

Identification of chemical constituents in Shenfu injection and study on anti-inflammatory activities of its poly- acetylene compounds / 中国药房

OBJECTIVE To study the chemical constituents in S henfu injection and the anti-inflammatory activities of its polyacetylene compounds. METHODS Shenfu injection was separated and purified by macroporous adsorption resin ，medium pressure liquid chromatography ，preparative thin layer chromatography and reversed-phase semi-preparative high-performance liquid chromatography，and the compound structure was identified according to the physicochemical properties and spectral data. RAW 264.7 cell inflammation model was used to evaluate the anti-inflammatory activities of polyacetylene compounds . The effects of active polyacetylene compounds on the expressions of cyclooxygenase- 2（COX-2）protein were evaluated by Western blot assay. RESULTS Twelves compounds were isolated and identified from Shenfu injection ，including 8 ginsenoside compounds ，i.e. ginsenoside Rg 1（1），ginsenoside Re （2），ginsenoside Rb 1（3），ginsenoside Rk 1（4），20（R）-ginsenoside Rh 1（5），20（S）-ginsenoside Rg3 （6），notoginsenoside R 1（7），panaxatriol（8）；4 polyacetylene compounds ，i.e.（3R，9R，10R）-panaxytriol（9），panaxydol（10）， heptadeca-1，8-dien-4，6-diyne-3，10-diol（11）and panaxynol （12）. Among 4 polyacetylene compounds ，only compound 10 had anti-inflammatory activity. Compound 10 was not toxic to normal RAW 264.7 cells；when the concentration of compound 10 ranged 12.5-50.0 μmol/L，it could significantly reverse the lipopolysaccharide-induced NO content increase in cell supernatant （P＜0.05 or P＜0.01）；when the concentration of co mpound 10 was 50.0 μmol/L，it could significantly reverse the lipopolysaccharide-induced protein expression increase of COX- 2 in cells （P＜0.05）. CONCLUSIONS Compounds 4，7，10-12 are identified and reported in Shenfu injection for the first time ，and panaxydol possesses a certain anti-inflammatory effect.

Effects of Shenfu Injection () on Inflammatory Response during Post-Resuscitation Myocardial Dysfunction after Cardiac Arrest in Swine / 中国结合医学杂志

OBJECTIVE@#To investigate whether Shenfu Injection (SFI, ) can alleviate post-resuscitation myocardial dysfunction by inhibiting the inflammatory response.@*METHODS@#After 8 min of ventricular fibrillation and 2 min of basic life support, 24 pigs were randomly divided into 3 groups (n=8), which were given intravenous bolus injections of SFI (1.0 mL/kg), epinephrine (EP, 0.02 mg/kg) and normal saline (SA), respectively. The animals were sacrificed at 24 h after restoration of spontaneous circulation (ROSC), and serum interleuking-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) mRNAs and proteins were determined by RT-PCR and Western blot, respectively.@*RESULTS@#Compared with the EP and the SA groups, the ultrastructure of myocardial cells were slightly damaged and the systolic function of the left ventricle was markedly improved in the SFI group at 24 h after ROSC (P<0.05). In addition, compared with the EP and SA groups, the SFI group also showed significantly reduced levels of serum IL-6 and TNF-α, protein and mRNA levels of myocardial NF- κB and TLR4 (P<0.05).@*CONCLUSIONS@#Activation of TLR4/NF-κB signaling pathway may be involved in the pathological mechanisms of post-resuscitation myocardial dysfunction. SFI may block NF-κB-mediated inflammatory response by reducing the activity of NF- κB and the level of TNF-α, thus playing a protective role in post-resuscitation myocardial dysfunction.

Intervention Effect of Shenfu Injection on the Nuclear Translocation of HMGB 1 in LPS-induced RAW 264.7 Cells / 中国药房

OBJECTIVE：To investigate the intervention effect of Shenfu i njection（SFI）on the nuclear translocation of high mobility group box 1（HMGB1） in lipopolysaccharide （LPS）-induced RAW 264.7 cells. METHODS ： Using LPS-induced RAW264.7 cells as objects ，the histone deacetylase inhibitor RGFP 966 as positive control ，CCK-8 assay was used to screen drug dosage，and the effects of low ，medium and high doses （3，6，12 μL/mL）of SFI on HMGB 1 nuclear translocation in RAW 264.7 cells were observed by immunofluorescence method ；mRNA expression of HMGB 1 in RAW 264.7 cells were detected by real time fluorescent PCR. Western blotting assay was used to determine protein expression of HMGB 1 and Toll-like receptor 4（TLR4）；the expression of HMGB 1 were compared between nucleus and cytoplasm. The levels of HMGB 1，IL-1β and TNF-α in supernatant of cells were detected by ELISA. RESULTS ：In blank control group ，HMGB1 was mainly located in the nucleus ；after LPS induction， HMGB1 migrated from nucleus to cytoplasm. Compared with blank control group ， mRNA and protein （No.81760738） expression of HMGB 1， protein expression of TLR 4 in RAW264.7 cells as well as the levels of HMGB 1，IL-1β and TNF-α in supernatant of cells were increased significantly in LPS group （P＜0.01）. The protein expression of HMGB 1 was decreased significantly in nucleus while was in creased significantly in cytoplasm （P＜0.01）. After SFI treatment ，the nuclear translocation and secretion of HMGB 1 were inhibited in different degrees ；compared with LPS group ，mRNA and protein expression of HMGB 1 in administration groups ，protein expression of TLR 4 in RAW 264.7 cells of positive control group ，SFI medium- and high-dose groups as well as the levels of HMGB 1，IL-1β and TNF-α in supernatant of cells in administration groups were decreased significantly （P＜0.01）. In positive control group ，SFI medium- and high-dose groups ，the protein expressions of HMGB1 in nucleus were increased significantly ，while protein expressions of HMGB 1 in cytoplasm were decreased significantly （P＜0.01）. CONCLUSIONS ：SFI may inhibit the nuclear translocation and secretion of HMGB 1 in RAW 264.7 cells，thus avoiding the activation of inflammatory pathways and the production of inflammatory factors ，so as to reduce the inflammatory response induced by LPS.

Effect of Shenfu injection on prognosis and quality of life of patients with vasovagal syncope / 国际中医中药杂志

Objective@#To observe the effect of different doses of Shenfu injection on prognosis and quality of life for patients with vasovagal syncope (VVS).@*Methods@#A total of 126 patients were randomly divided into 3 groups. The control group (n=38) were treated by western medicine comprehensive therapy with tilting training. The low and high dose Shenfu injection groups were treated by Shenfu injection 40 ml/d (n=44) and 120 ml/d (n=44) on the treatment basis of control group. All the groups were treated for 14 days. The patients were followed up for 1 year after discharge. The relapse rate of syncope, quality of life social support rating scale (SSRS), effective rate of treatment, time of stable blood pressure, time of stable heart rate, recovery time of autonomic nervous disorder and adverse reactions were observed in each groups.@*Results@#The total effective rate was 47.4% (18/38) in the control group, 72.7% (32/44) in the low dose group, and 90.9% (40/44) in the high dose group. The difference between the three groups was statistically significant (χ2=18.997, P<0.01), and the total effective rate of Shenfu injection high-dose group was significantly higher than that of low-dose group (P<0.05). After treatment, there were significant differences in the recovery time of blood pressure, heart rate and autonomic nervous disorder among the three groups (F=19.165, 158.428, 33.405, P<0.01). The above indicators in the high dose group of Shenfu injection were significantly higher than the low dose group (t=-4.020, -5.180, -5.307, P<0.05). After 1 year of follow-up, the recurrence rate of the control group was 61.1% (11/18), the low-dose group was 18.8% (6/32), and the high-dose group was 5% (2/40), where there was significant difference among all the groups (χ2=20.886, P<0.01). The quality of life scores were compared for 1 year among the 3 groups, and the difference was statistically significant (F=23.025, P<0.01).@*Conclusions@#The Shenfu injection combined with Western medicine comprehensive therapy can improve the prognosis and quality of life of patients with VVS, and the improvement of each indicator of daily dosage of 120 ml is better than the daily dosage of 40 ml Shenfu injection.

Improvement and Anti-inflammation Mechanism of Shenfu Injection on Lung Tissue in Endotoxin Shock Model Rats / 中国药房

OBJECTIVE： To study the improvement and anti-inflammation mechanism of Shenfu injection on lung tissue of endotoxin shock model rats. METHODS： Totally 48 rats were randomized into control group，model group，dexamethasone group （positive control，1 mg/kg） and Shenfu injection low-dose，medium-dose and high-dose groups （5，10，15 mL/kg），with 8 rats in each group. Except for normal group， other groups were given intraperitoneal injection of lipopolysaccharide （LPS） to induce endotoxin shock model. After modeling， each group was given relevant medicine once intraperitoneally. 24 h after medication， HE staining was used to observe pathological changes of lung tissue in rats and pathological scoring was conducted. RT-PCR was used to determine mRNA levels of P65 and P50 proteins related to NF-κB signaling pathway. Western blot assay was used to determine the expression levels of P65 and P50 proteins in lung tissue， and the expression levels of P65 protein in nucleus and cytoplasm of lung tissue were also determined. The level of TNF-α in plasma in rats were determined by ELISA. RESULTS： Compared with control group， alveolar septum became thicker， obvious vascular engorgement was found， and a large number of neutrophils infiltrated the interstitium in model group. Histopathological score， mRNA and protein expression levels of P65 and P50 in lung tissues were increased significantly （P＜0.01 or P＜0.001）； the protein expression of levels P65 in nucleus and cytoplasm and level of TNF-α in plasma were increased significantly （P＜0.001）. Compared with model group， alveolar structure of rats in dexamethasone group and Shenfu injection medium-dose and high-dose groups was complete， no obvious bleeding was observed， and the degree of inflammatory cell infiltration was improved significantly. Histopathological score， mRNA and protein expression levels of P65 and P50 in lung tissue and level of TNF-α in plasma were decreased significantly （P＜0.05 or P＜0.01 or P＜0.001）. The protein expression level of P65 in nucleus and cytoplasm of lung tissue were decreased significantly in dexamethasone group and Shenfu injection low-dose and medium-dose groups were decreased significantly （P＜0.05 or P＜0.01 or P＜0.001）. CONCLUSIONS： Shenfu injection can decrease mRNA and protein expression levels of P65 and P50 in lung tissue， level of TNF-α in plasma， and protect lung tissue of endotoxin shock rats.

Effect of traditional Chinese medicine syndrome differentiation and standard bundle therapy in patients with septic shock / 中华危重病急救医学

Objective To evaluate an effective and feasible quantitative evaluation table of traditional Chinese medicine (TCM) syndrome differentiation, and to observe the effect of combination of TCM syndrome differentiation and standard bundle therapy in patients with septic shock. Methods A prospective randomized controlled trial was conducted. The septic shock patients with acute deficiency syndrome admitted to department of critical care medicine of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 1st, 2016 to December 31st, 2017 were enrolled. The patients were randomly divided into control group and Shenfu group. The patients in both groups received early application of standardized bundle therapy; those in Shenfu group received 60 mL Shenfu injection infusion in addition for 7 days. The TCM syndrome score was evaluated by classification and scoring method of TCM symptoms. The circulation and tissue perfusion, severity of disease, organ function, inflammation response, adjuvant treatment and 28-day mortality were compared between the two groups. Results A total of 50 patients with septic shock were enrolled in the analysis, 25 in control group and 25 in Shenfu group. The markedly effective rate of TCM symptoms score in Shenfu group was significantly higher than that in control group [60.0% (15/25) vs. 16.0% (4/25), P < 0.01]. There was no significant difference in all parameters before treatment between the two groups. After treatment, the observation indexes of both groups were improved. Compared with control group, the mean arterial pressure (MAP) in Shenfu group increased more significantly [mmHg (1 mmHg = 0.133 kPa): 13.0 (2.5, 28.5) vs. 6.0 (0, 13.5)], the lactate (Lac) and procalcitonin (PCT) decreased more significantly [Lac (mmol/L): 0.8 (0.1, 3.7) vs. 0.5 (-0.6, 1.7), PCT (μg/L): 2.0 (0.7, 32.3) vs. 0 (-1.8, 3.8)], activated partial thromboplastin time (APTT) was shortened more significantly [s: 8.5 (0, 12.9) vs. 0 (-7.2, 10.0)], and interleukins (IL-2 receptor and IL-6) levels decreased more significantly [IL-2 receptor (ng/L):1 031.0 (533.0, 1 840.0) vs. 525.5 (186.0, 1 166.8), IL-6 (ng/L): 153.1 (21.4, 406.8) vs. 35.1 (16.3, 110.1)] with significant differences (all P < 0.05). There was no significant difference in the use time of vasoactive drugs, duration of mechanical ventilation, severity of the disease or 28-day mortality between the two groups. However, the use time of vasoactive drugs in Shenfu group was shorter than that in control group (days: 5.48±4.81 vs. 8.28±7.83), and the 28-day mortality was decreased [8.0% (2/25) vs. 20.0% (5/25)]. Conclusions TCM syndrome score is helpful to evaluate the effect of TCM syndrome differentiation and treatment, and it is effective and feasible in clinical application. Septic shock patients treated with TCM syndrome differentiation and treatment combined with standard bundle therapy were significantly improved in circulation, tissue perfusion, coagulation function and inflammation reaction.

Effect of Shenfu injection on prognosis and quality of life of patients with vasovagal syncope / 国际中医中药杂志

Objective To observe the effect of different doses of Shenfu injection on prognosis and quality of life for patients with vasovagal syncope (VVS). Methods A total of 126 patients were randomly divided into 3 groups. The control group (n=38) were treated by western medicine comprehensive therapy with tilting training. The low and high dose Shenfu injection groups were treated by Shenfu injection 40 ml/d (n=44) and 120 ml/d (n=44) on the treatment basis of control group. All the groups were treated for 14 days. The patients were followed up for 1 year after discharge. The relapse rate of syncope, quality of life social support rating scale (SSRS), effective rate of treatment, time of stable blood pressure, time of stable heart rate, recovery time of autonomic nervous disorder and adverse reactions were observed in each groups. Results The total effective rate was 47.4% (18/38) in the control group, 72.7% (32/44) in the low dose group, and 90.9% (40/44) in the high dose group. The difference between the three groups was statistically significant (χ2=18.997, P<0.01), and the total effective rate of Shenfu injection high-dose group was significantly higher than that of low-dose group (P<0.05). After treatment, there were significant differences in the recovery time of blood pressure, heart rate and autonomic nervous disorder among the three groups (F=19.165, 158.428, 33.405, P<0.01). The above indicators in the high dose group of Shenfu injection were significantly higher than the low dose group (t=-4.020, -5.180, -5.307, P<0.05). After 1 year of follow-up, the recurrence rate of the control group was 61.1% (11/18), the low-dose group was 18.8% (6/32), and the high-dose group was 5% (2/40), where there was significant difference among all the groups (χ2=20.886, P<0.01). The quality of life scores were compared for 1 year among the 3 groups, and the difference was statistically significant (F=23.025, P<0.01). Conclusions The Shenfu injection combined with Western medicine comprehensive therapy can improve the prognosis and quality of life of patients with VVS, and the improvement of each indicator of daily dosage of 120 ml is better than the daily dosage of 40 ml Shenfu injection.

The methodological quality assessment of systematic review/meta-analysis of Shenfu injection in treating heart failure based on AMSTAR 2 / 国际中医中药杂志

Objective To evaluate the methodological quality of the systematic evaluation literature of Shenfu injection in the treatment of heart failure with AMSTAR 2 statement.Methods Searching includes Chongqing VIP Database,China Knowledge Network Database,China Biomedical Literature Database.Wanfang Database,PubMed Database,Cochrane library database,search time limit from database construction to Dec 31 st,2017.Two evaluators independently screened the literature based on inclusion and exclusion criteria,and applied the AMSTAR 2 statement list to evaluate all the systematic review literatures included.Results A total of 9 articles were included in the study,and the average reporting rate is 43.75％.The low-reporting domains focused on the review protocols prior to the research,the types of the included studies,the list of excluded documents,the evaluation and causes of bias of risks and heterogeneity,and reports on funds and conflicts of interest.Conclusions The average reporting rate is low overall,indicating that the current reports of the systematic review has defects,which affects the credibility of the systematic review and the use of evidence.For the determination of clinical decision-making,it is recommended that researchers should follow the AMSTAR 2 statement to improve the methodological or reporting quality.

The clinical efficacy and mechanism of Shenfu injection combined with azithromycin on infantile mycoplasma pneumonia / 西安交通大学学报(医学版)

Objective: To evaluate the clinical efficacy and molecular mechanism of Shenfu combined with azithromycin on infantile mycoplasma pneumonia. Methods: Totally 80 children with mycoplasma pneumonia treated in Children's Hospital Affiliated to Soochow University from June 2016 to June 2017 were selected and randomly divided into two groups with 40 in each. Azithromycin was provided in both groups. Shenfu was administered in the observation group. The clinical efficacy, immunological functions and miR-181a level, and related molecular markers of all the subjects were observed. Lentivirus was used to transfer miR-181a into human T lymphocytes to observe its effects on lymphocyte proliferation, cytokine secretion level and related signaling pathways. Results: Compared with the normal group after treatment, the clinical efficacy, T lymphocyte subset proportion and inflammation cytokines were significantly increased (P<0.05), and the time of clinical symptoms remission was significantly decreased in the observation group after treatment (P<0.05). In addition, the content of miR-181a (9.3±5.3) in lymphocytes of the observation group after treatment was significantly lower than that (12.2±4.5) of the control group after treatment (P<0.05). In vitro assay revealed that miR-181a was significantly decreased lymphocyte proliferation and the ability of secretory cytokine. Luciferase reporter assay demonstrated that miR-181a could inhibit KRAS, NRAS and MAPK1 expressions, thus down-regulating P-AKT and P-MEK phosphorylation. Conclusion: Shenfu combined with azithromycin can effectively improve immunity functions and its mechanism might be related to the level of miR-181a in lymphocytes.

Effect of Shenfu Injection on acute kidney injury in children with congenital heart disease after operation / 中国中西医结合急救杂志

Objective To investigate the effect of Shenfu Injection on acute renal injury (AKI) in children with congenital heart disease after operation. Methods Sixty-two children with atrial or ventricular septal defect, treated in Affiliated Hospital of Southwest Medical University from August 2016 to December 2018, were divided into two groups according to different treatment methods, such as conventional Western medicine treatment group and Shenfu Injection group, with 31 cases in each group. The children in Shenfu Injection group were given 20 mL Shenfu Injection from the beginning of anesthesia induction to the end of cardiopulmonary bypass, the children in Western medicine conventional treatment group were pumped with the same volume of normal saline. The anesthesia time, total operation time, cardiopalmonary bypass time, aortic clamping time, and the use of milrinone, dopamine, epinephrine, sodium nitroprusside and other drugs in the two groups were observed. The serum creatinine (SCr) level was measured by chemiluminescence method before operation (T0), at the beginning of operation (T1), at the beginning of cardiopulmonary bypass (T2), at the end of cardiopulmonary bypass (T3) and at the end of operation (T4), and the glomerular filtration rate (eGFR) was calculated. The mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), adrenaline (E) and noradrenaline (NE) in two groups were recorded at each time point. Results There was no significant difference in anesthesia time, total operation time, cardiopalmonary bypass time, aortic clamping time and the use of milrinone, dopamine, E and sodium nitroprusside between the Shenfu Injection group and Western medicine conventional treatment group (all P > 0.05). There was no significant difference in HR and CVP between the two groups at T0-T4 (all P > 0.05). There was no significant difference in MAP level between the two groups at T0 and T1( both P > 0.05), with the time prolonging, the MAP level of Western medicine conventional treatment group was significantly lower than that of T0, while MAP level of Shenfu Injection group was significantly higher than that of T0. At T2, the MAP level of Shenfu Injection group was significantly higher than that of the Western medicine conventional treatment group [mmHg (1 mmHg = 0.133 kPa): 66.6±6.5 vs. 53.1±6.7, P < 0.05]. There was no significant difference in E and NE between the two groups at T0 and T1 (P > 0.05), with the time prolonging, both E and NE decreased compared with those at T0 (both P < 0.05), but there was no significant difference at the same time point (all P > 0.05). At T0, there was no significant difference in SCr and eGFRs between the two groups (both P > 0.05), at T1, the SCr levels of two groups were significantly higher than those at T0, but the SCr level of Shenfu Injection group was significantly lower than that of Western medicine conventional treatment group (μmol/L: 42.43±15.91 vs. 56.58±16.80, all P < 0.05). From T2, the SCr levels of two groups began to gradually reduce, but it was still significantly higher than those at T0, the two groups reached the lowest level at T4, and the level of SCr in Shenfu Injection group was significantly lower than that of Western medicine conventional treatment group (μmol/L: 36.24±9.72 vs. 46.85±15.91, P < 0.05). Compared with T0, the eGFRs levels of the two groups were significantly lower at T1-T4, but gradually increased with time, reached the highest level at T4, and the eGFRs level of Shenfu Injection group was significantly higher than that of Western medicine conventional treatment group (mL·min-1·1.73 m-2: 113.7±12.1 vs. 79.6±12.5, P < 0.05). The incidence of AKI in Shenfu Injection group was significantly lower than that in Western medicine conventional treatment group [22.58% (7/31) vs. 64.52% (20/31), P < 0.05]. Conclusion Shenfu Injection can reduce the incidence of AKI in children with congenital heart disease after operation.

Study on protection of a Shenfu injection against myocardial ischemia-reperfusion arrhythmias in aged mice / 中华老年医学杂志

Objective@#To investigate the protective effects of pretreatment with a Shenfu(SF)injection on arrhythmias induced by myocardial ischemia-reperfusion(IR)injury in aged mice.@*Methods@#Thirty 18-month-old C57BL/6J mice were randomly divided into 3 groups(n=10, each group): the sham treatment group(receiving sham operation without thoracotomy), the IR group(undergoing the ligation of the left anterior descending coronary artery with ischemia for 30 min and reperfusion for 2 h)and the SF group(receiving SF intraperitoneal injection of 10 ml/kg 30 min before thoracotomy and the same treatment as the IR group). Arrhythmias were monitored, and serum levels of creatine kinase-isoenzyme(CK-MB), troponin(cTnI)and tumor necrosis factor α(TNFα), and the ratio of myocardial connexin 43(Cx43)phosphorylation(ser368)to total protein(p-Cx43/t-Cx43)were detected in the three groups.@*Results@#Ventricular arrhythmias occurred in the IR and SF groups.Compared with the IR group, ventricular arrhythmias in the SF group were alleviated, the frequency of ventricular premature systolic episodes was reduced(36.6±13.5 times vs. 48.4±22.1 times), the frequency of ventricular tachycardia/fibrillation decreased(3.4±1.8 times vs. 7.6±3.5 times), and the total duration of ventricular tachycardia/fibrillation episodes was shortened(8.9±4.5 times vs. 17.7±5.1 times)in the SF group(P<0.05), but there was no significant difference in arrhythmia scores(1.8±1.2 points vs. 1.9±1.7 points, P>0.05)between the two groups.Compared with the sham treatment group, serum levels of CK-MB, cTnI and myocardial TNF(increased in the IR and SF groups(P<0.05), and their levels were lower in the SF group than in the IR group(P<0.05). Compared with the sham treatment group, the ratio of Cx43 ser368/total protein was lower in the IR and SF groups, but was higher in the SF group than in the IR group(P<0.05).@*Conclusions@#SF pretreatment can significantly reduce IR-induced arrhythmias in aged mice possibly by reducing TNF(and up-regulating the phosphorylation activity of Cx43.