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Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The "gut-heart" axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5mg kg-1⋅d-1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating cometabolism and regulating the TMAO-inflammation axis. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion. Method: This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization. Results: A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days–6.0 days vs. median=5.0 days, IQR: 3.0 days–8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3–2.0 mmol/L vs. median=0.0 mmol/L, IQR: −0.2 to 0.8 mmol/L, respectively; P

To explore the anti-inflammatory effect and potential mechanism of Shenfu injection (SFI) on lipopolysaccharides(LPS) induced RAW264. 7 cells. Inflammatory cell model in wild type RAW264. 7 cells were induced by using LPS. Pro-inflammatory factors (including iNOS, IL-1β and TNF-α) were tested by using RT-qPCR, WB and ELISA to evaluate the anti-inflammatory effect of SFI. HMGB1+ (over-expressing HMGB1)-RAW264. 7 cells and HMGB1m(mutation of nuclear localization sites to prevent the extra-nuclear migration)-RAW264. 7 cells were constructed to explore the potential mechanism. After stimulating by LPS, the level of HMGB1, TNF-α, IL-1β and iNOS were tested by RT-qPCR and WB, and the translocation of HMGB1 were tested by immunofluorescence in wild type, HMGB1+ and HMGB1m-RAW264. 7 cells. Then mammalian two-hybrid approach and co-immunoprecipitation method were carried out to detect the binding rates among HMGB1, P65 and P50. The results indicate that the expression of iNOS, IL-1β, and TNF-α in LPS induced RAW264. 7 cells were inhibited by SFI (P <0. 01). The extracellular migration of HMGB1 was inhibited also by SFI, then resulting in the high expression of HMGB1 in the nucleus. the tolerance of RAW264. 7 cells to LPS was increased by the high expression of HMGB1 in the nucleus. The TNF-α and IL-1β of HMGB1+ - RAW264. 7 cells induced by LPS (1 μg/ mL) were both increased, which was reversed by SFI. The TNF-α and IL-1β of HMGB1m-RAW264. 7 cells had no difference with control group. SFI increased the binding rate of HMGB1 to P65 and HMGB1 to P50 in the nucleus (P <0. 01), and reduced the binding rate of P50 to P65. The results show that the above results suggested that the inflammatory response of LPS induced RAW264. 7 cell was inhibited by SFI. Its pathway of action may be through inhibiting the translocation of HMGB1, competitively binding to P65 and P50, as well as reducing the formation of P65-P50 dimers. [ABSTRACT FROM AUTHOR]

Background: Shenfu Injection (SFI) has emerged as a prevalent therapeutic intervention in clinical practice for the management of acute pancreatitis (AP). The purpose of this research was to investigate and validate the potential mechanisms of SFI in the treatment of AP through network pharmacology. Methods: Network pharmacology was adopted to investigate the potential targets and mechanisms of SFI in the treatment of AP. Molecular docking was employed to evaluate the binding affinity between active components and targets. Single-cell transcriptome analysis was conducted to explore the cell types associated with SFI treatment in AP. In vitro and in vivo models of AP were induced by caerulein. The histopathological changes were observed by HE staining. Cell apoptosis was detected using flow cytometry and Tunel staining. Cell viability was assessed using CCK-8 assay. Western blot and ELISA were used to detect the protein expression and inflammatory cytokines, respectively. Results: A total of 104 SFI active components were obtained, of which 29 targeted 76 genes. After intersecting with 3370 AP-related genes, 42 SFI treatment AP potential targets were identified. Enrichment analysis revealed that these targets were associated with cell apoptosis, necroptosis, and multiple signal transduction pathways, such as p53, IL-17 and TNF signal pathways, etc. Molecular docking demonstrated that the active components of SFI had good binding affinity with the corresponding targets and the binding ability of NGF and aromadendrene was the strongest. Bioinformatics analysis revealed that SFI treatment in AP is associated with various cell types, including acinar cells, endothelial cells, T cells, dendritic cells, ductal cells, and mesenchymal cells. Furthermore, in vitro experiments demonstrated that SFI induces acinar cell apoptosis in a dose-dependent manner, accompanied by increased expression of cleaved-caspase3/caspase3 and cleaved-caspase8/caspase8 proteins, and inhibition of inflammatory cytokine (TNF-ɑ, IL-1β, and PTGS2) expression. In vivo experiments demonstrated that SFI improved histopathological alterations, reduces inflammation, and promotes apoptosis and the expression of cleaved-casp3 and cleaved-casp8 in AP rats. Conclusions: This study elucidated the multi-component, multi-target, and multi-cellular characteristics of SFI in the treatment of AP, and confirmed its mechanism of promoting acinar cell apoptosis.

Shenfu injection (SFI), composed of ginseng and aconite, is a Chinese patent developed from the classic traditional prescription Shenfu Decoction created more than 700 years ago. SFI has been widely used in China for over 30 years for treating cardiovascular diseases. The main components in it include ginsenosides and aconitum alkaloids. In recent years, the role of SFI in the treatment of cardiovascular diseases has attracted much attention. The pharmacological effects and therapeutic applications of SFI in cardiovascular diseases are summarized here, highlighting pharmacological features and potential mechanisms developments, confirming that SFI can play a role in multiple ways and is a promising drug for treating cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Shenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the therapeutic potential of the SF injection in gut ischemia-reperfusion (I/R) injury after severe hemorrhagic shock (SHS) and resuscitation. Furthermore, we also investigated the optimal adm？ inistration timing. Methods: Twenty-four male SD rats were randomly divided into four groups: Sham group (sham, n = 6), Control group (n = 6), SF injection group (SF, n = 6), and Delayed Shenfu injection administration group (SF-delay, n = 6). In SHS and resuscitation model, rats were induced by blood draw to a mean arterial pressure (MAP) of 40 ± 5 mmHg within 1 h and then maintained for 40 min; HR, MAP ‘were recorded, microcirculation index [De Backer score, perfused small vessel density (PSVD), total vessel density (TVD), microcirculation flow index score (MFI), flow heterogeneity index (HI)] were analyzed. The blood gas index was detected, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), malondialdehyde (MDA) were measured by ELISA; ZO-1, and claudin-1 were measured by Western blotting. In addition, hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining pathological sections of the intestinal mucosal tissues were also performed. Results: SF injection increased the MAP, relieved the metabolic acidosis degree associated with the hypoperfusion, and improved the intestinal microcirculatory density and perfusion quality after I/R injury. The expression of DAO, MDA in intestinal tissue, and plasma IL-6, TNF-α significantly decreased in the SF injection group compared to the control group. The concentration of ZO-1 and claudin-1 is also higher in the SF injection group. In addition, the HE and PAS staining results also showed that SF injection could decrease mucosal damage and maintain the structure. In the SF-delay group, the degree of intestinal tissue damage was intermediate between that of the control group and SF injection group. Conclusions: SF injection protect the intestine from I/R injury induced by SHS and resuscitation, the mechanism of which might be through improving intestinal microcirculation, reducing the excessive release of inflammatory factors and increasing intestinal mucosal permeability. Furthermore, the protection effect is more pronounced if administration during the initial resuscitation phase.

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. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect and mechanism of Shenfu Injection on heart failure rats based on the PI3K-AKT-mTOR signaling pathway. Methods: Sixty SD rats were randomly divided into a normal control group (n=20）, a heart failure model group (n=20）, and a Shenfu injection treatment group (n=20）. The normal control group did not receive any treatment, while the other two groups were treated with abdominal aortic constriction to construct a heart failure model. The heart failure model group was given sodium chloride solution, and the Shenfu injection treatment group was given Shenfu injection. Compare the cardiac function, oxidative stress, inflammatory factors, and P13K Akt m TOR expression of rats in each group. Results: Compared to the normal control group, the levels of left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) in the Shenfu injection treatment group and heart failure model group increased sequentially, while the levels of left ventricular ejection fraction (LVEF) decreased sequentially (P＜0.05）. Compared to the normal control group, the level of serum malondialdehyde (MDA) in the Shenfu injection treatment group and the heart failure model group increased in turn, and the level of serum superoxide dismutase (SOD) decreased in turn (P＜0.05）. Compared to the normal control group, the Shenfu Injection treatment group and the heart failure model group had serum interleukin-6 (IL-6) and interleukin-1 levels β (IL-1 β）, Tumor Necrosis Factor-α (TNF-α) The levels increased sequentially (P＜0.05）. Compared to the normal control group, the expression of P13K-Akt-mTOR in the Shenfu Injection treatment group and heart failure model group decreased sequentially (P＜0.05）. Conclusion: Shenfu Injection can protect the cardiac function of heart failure rats, alleviate oxidative stress response, and inhibit the expression of inflammatory factors. Its mechanism of action may be related to the activation of the P13K-Akt-mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Shenfu Injection (SFI) derived from Shenfu decoction, has been widely used for treating heart failure in China. This meta-analysis aimed to assess the effect of SFI as an adjuvant therapy on quality of life in patients with chronic heart failure (CHF). Methods: A systematic literature search was conducted in CKNI, VIP, Wanfang, Sinomed, Cochrane Library, PubMed, and Embase database until March 16, 2023. Randomized controlled trials (RCTs) evaluating the effect of SFI plus conventional therapy versus conventional therapy alone for treating CHF were included. Outcome measures were quality of life defineded by the Minnesota Living with Heart Failure questionnaire (MLHFQ), left ventricular ejection fraction (LVEF), 6-min walking distance, and blood brain natriuretic peptide (BNP)/N-terminal pro-brain natriuretic peptide (NT-proBNP) level. Results: Thirteen RCTs enrolling 1042 CHF patients were included. SFI plus conventional therapy significantly reduced the total MLHFQ score (mean difference [MD] −8.69 points; 95% confidence intervals [CI] −13.46 to −3.91) compared with the conventional therapy alone. Moreover, adjuvant treatment with SFI significantly improved the 6-min walking distance (MD 65.42 m; 95% CI 44.23 to 86.62), LVEF (MD 3.89; 95% CI 1.03 to 6.75), and blood level of BNP/NT-proBNP (SMD -1.73; 95% CI -2.43 to −1.03). Conclusions: Adjuvant treatment with SFI can achieve additional benefits in improving quality of life and exercise tolerance in patients with CHF. These beneficial effects of SFI may correlate with its improving cardiac function. However, our findings should be interpreted with presence of significant heterogeneity and suboptimal quality of the analyzed trials.

Objective: This systematic review and meta-analysis aimed to investigate the adjuvant effect and safety of Shenfu injection (SFI) on the treatment of post-acute myocardial infarction heart failure (PAMIHF). Methods: Seven databases were searched to identify randomized controlled trials (RCTs) associated with SFI and PAMIHF treatment from May 1990 to May 2022. Primary outcomes included NT-proBNP and left ventricular ejection fraction (LVEF), and secondary outcomes included total effective rate, BNP, heart rate (HR), cardiac output (CO), and adverse event (AE). The risk of bias evaluation was assessed by the ROB2 tool, meta-analysis, subgroup analysis, sensitivity analysis, and publication bias were conducted by RevMan5.3 software, and the Grade of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to evaluate the quality of evidence of meta results. Results: A total of 36 studies with 3231 PAMIHF patients were included. The meta results suggested that adjuvant SFI therapy was superior to conventional medical therapy alone. It improved the total effective rate [RR = 1.33; 95% CI (1.25.1.40); p < 0.00001], increased LVEF [SMD = 0.98; 95% CI (0.71, 1.24); p < 0.00001], and decreased HR [SMD = -1.14; 95% CI (-1.28, -0.99); p < 0.00001]. In addition, adjuvant SFI therapy (9.73%, 66/678) had a rate of AE lower than that of conventional medical therapy alone (21.7%, 147/677) when regarding safety [RR = 0.45; 95% CI (0.35, 0.57); p < 0.00001]. The quality of the evidence for the outcomes was rated from "very low" to "moderate." Conclusion: Adjuvant SFI therapy was safer to improve the total effective rate and the heart function of PAMIHF patients. However, well-designed RCTs were needed to confirm the efficacy and safety of adjuvant SFI therapy in PAMIHF treatment due to the low quality of the evidence for the outcomes caused by a small sample size and unclear risk of bias existed in included studies. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ display_record.php?RecordID=151856), identifier CRD42020151856. [ABSTRACT FROM AUTHOR]

Background: Septic shock has increasingly become a cause of death threatening human survival. Shenfu Injection (SFI), a patented Chinese medicine, has been widely used in the treatment of patients with sepsis and cardiovascular diseases domestically. We sought to examine whether combination therapy with SFI can improve clinical outcomes in critically ill patients undergoing mechanical ventilation (MV). Methods: This real-world, multicenter retrospective trial enrolled consecutive adult patients with sepsis requiring MV from four medical/surgical intensive care units (ICUs) in China between August 2016 and September 2021. Patients were identified from the medical information department database of each center and assigned to either of two groups (SFI or control) on the basis of the initial treatment received. The primary outcome was 28-day all-cause mortality, and the durations of vasopressor therapy and MV, the ICU length of stay, and costs were assessed as secondary outcomes. Subsequently, we performed a metaanalysis of randomized controlled trials (RCTs) on SFI published before July 2021 to verify our conclusions. Results: 2311 mechanically ventilated patients with septic shock (1128 patients in the SFI group and 1183 in the control group) were analyzed. The survival probability during the first 28 days after admission in the SFI group was greater than that in the control group [p < 0.01 by log-rank test; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.39-0.72]. Patients in the SFI group also experienced a significantly reduced duration of vasopressor therapy [7.28 (95% CI, 6.14-8.42) vs. 12.06 (95% CI, 10.71-13.41) days, p < 0.001], more ventilator-free days [6.49 (95% CI, 5.42-7.55) vs. 10.84 (95% CI, 9.59-12.09).ō. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the mechanism of Shenfu injection in the treatment of hemorrhagic shock based on network pharmacology and molecular docking technology. METHODS: The main components and action targets of Shenfu injection were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Hemorrhagic shock related targets were obtained by searching the databases of GeneCards, Online Mendelian Inheritance in Man, therapeutic target database and Drugbank. The drug targets and disease targets were intersected and Venn diagram was drawn. The intersection targets were uploaded to STRING for visualization to obtain the proteinprotein interaction ( PPI) network diagram. Cytoscape 3. 9. 1 was used to construct the “ drug-component-targetdisease” network diagram. Gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed by using R 4. 2. 1. Pymol 2. 4. 0 and AutoDock Tools 1. 5. 7 were used for molecular docking. RESULTS: The two components of Shenfu injection were ginseng and aconite extract, 25 active components were screened, and 30 common targets were obtained after intersected with drug targets and disease targets. The PPI diagram showed that the degree of TNF, CASP3, IL-1β, PTGS2, ESR1 and CASP8 were higher. The network diagram of Shenfu injection-active component-gene target-disease showed that Beta-sitosterol, Ginsenoside rh2, Deltoin, Karanjin and PTGS2, NCOA2, PTGS1, ADRB2 were of high biological importance. GO functional enrichment analysis mainly focused on the regulation of apoptosis and inflammatory factors. KEGG pathway enrichment analysis showed that influenza A and other pathways were associated with hemorrhagic shock. In molecular docking, the change of intermolecular binding energy of molecular docking confirmed that the effective components of Shenfu injection could bind stably to the target related to hemorrhagic shock. CONCLUSIONS: Shenfu injection has the characteristics of multi-components and multi-targets in the treatment of hemorrhagic shock, which may be related to its reduction of cell apoptosis and inhibition of inflammation. [ABSTRACT FROM AUTHOR]

Objective: To assess the effects of Shenfu Injection (参附注射液, SFI) on blood lactate, and secondarily its effect on the lactate clearance (LC) in patients with post cardiac arrest syndrome (PCAS). Methods: The present study is a post hoc study of a randomized, assessor-blinded, controlled trial. Patients experienced in-hospital cardiac arrest between 2012 and 2015 were included in the predefined post hoc analyses. Of 1,022 patients enrolled, a total of 978 patients were allocated to the control group (486 cases) and SFI (492 cases) group, receiving standardized post-resuscitation care bundle (PRCB) treatment or PRCB combined with SFI (100 mL/d), respectively. Patients' serum lactate was measured simultaneously with artery blood gas, lactate clearance (LC) was calculated on days 1, 3, and 7 after admission and compared between groups. Lactate and LC were also compared between the survivors and non-survivors according to the 28-d mortality, as well as the survivors and non-survivors subgroups both in the SFI and control groups. Results: In both groups, compared with pre-treatment levels, mean arterial pressure (MAP) and PaO2 were significantly improved on 1, 3, 7 d after treatment (P<0.05), while heart rate (HR) and blood glucose levels were significantly decreased on 1, 3 and 7 d after treatment (P<0.05). compared with control group, SFI treatment improved the values of MAP and PaO2 (P<0.05), and significantly decreased the levels of HR and the blood glucose level on 3 and 7 d after treatment (P<0.05). Compared with the control group, lactate levels decreased faster in the SFI group versus the control group on 3 and 7 d (P<0.05). From initiation of treatment and the following 3 and 7 d, SFI treatment greatly increased the LC compared with that in the control group (P<0.05). Compared with survivors, non-survivors had higher admission lactate levels (7.3 ±1.1 mmol/L vs. 5.5 ±2.3 mmol/L; P<0.01), higher lactate levels on days 1, 3 and 7 (P<0.05), and LC were decreased significantly on 3 and 7 d after treatment (P<0.05). Similar results were also found both in the SFI and control groups between survivors and non-survivors subgroups. Conclusion: SFI in combination with PRCB treatment is effective at lowering lactate level and resulted in increasing LC in a targeted population of PCAS patients. [ABSTRACT FROM AUTHOR]

Abstract Background Levosimendan can improve clinical symptoms and the cardiorenal rescue success rate, and stabilize hemodynamic parameters in individuals suffering from acute decompensated heart failure. In addition, Shenfu injection (SFI) has been shown to protect the ischemic heart and enhance myocardial contractility. Methods For this randomized control single-blind study, 101 patients with acute decompensated heart failure (ADHF) were enrolled and randomly assigned to control levosimendan (n = 51) and levosimendan + SFI injection (n = 50) groups. Attending physicians were not blinded for which arm the patients were allocated. Blood pressure, heart rate, the electrocardiogram, respiratory rate, fluid intake and urine output were all recorded 2 h and 24 h after drug infusions had commenced, and the cardiac index (CI) was monitored by ultrasonic cardiac output monitors. Results Median blood pressure was markedly increased in the levosimendan + SFI group after 2 h and 24 h from the initiation of infusions compared to levosimendan administration alone. Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P

Sepsis is a life-threatening organ dysfunction caused by an exaggerated response to infection. In the lungs, one of the most susceptible organs, this can manifest as acute respiratory distress syndrome (ARDS). Shenfu (SF) injection is a prominent traditional Chinese medicine used to treat sepsis. However, the exact mechanism of its action has rarely been reported in the literature. In the present study, we detected the protective effect of SF injection on sepsis-induced ARDS and explored its underlying mechanism. We investigated the potential targets and regulatory mechanisms of SF injections using a combination of network pharmacology and RNA sequencing. This study was conducted both in vivo and in vitro using a mouse model of ARDS and lipopolysaccharide (LPS)-stimulated MLE-12 cells, respectively. The results showed that SF injection could effectively inhibit inflammation, oxidative stress, and apoptosis to alleviate LPS-induced ARDS. SF inhibited the PI3K-AKT pathway, which controls autophagy and apoptosis. Subsequently, MLE-12 cells were treated with 3-methyladenine to assess its effects on autophagy and apoptosis. Additional experiments were conducted by adding rapamycin, an mTOR antagonist, or SC79, an AKT agonist, to investigate the effects of SF injection on autophagy, apoptosis, and the PI3K-AKT pathway. Overall, we found that SF administration could enhance autophagic activity, reduce apoptosis, suppress inflammatory responses and oxidative stress, and inhibit the PI3K-AKT pathway, thus ameliorating sepsis-induced ARDS. SF injection can activate autophagy, alleviate the inflammatory response, relieve oxidative stress, and reduce apoptosis by suppressing the PI3K/AKT pathway, making it a promising candidate for treating sepsis-induced ARDS. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of Shenfu injection in treating patients with acute internal watershed cerebral infarction. Methods Totally 154 patients with AIWCI admitted to the Department of Encephalopathy of Dongzhimen Hospital from October 2018 to October 2020 were divided into the experimental group (n=96)and the control group(n=58). All cases received a comprehensive treatment including anti-platelet aggregation, lowering blood lipid, regulating blood pressure, replenishing blood volume, improving microcirculation and protecting brain cells. Patients in the experimental group were additionally given Shenfu injection for 14 days as a course of treatment. Before and after treatment, the National Institutes of Health Stroke Scale (NIHSS) was used to score the neurological impairment, and transcranial doppler (TCD) was used to measure the blood flow velocity of the middle cerebral artery at the affected side. Results The blood flow velocity of middle cerebral artery in 2 groups was increased after treatment, and the experimental group had a better improvement in Peak systolic velocity (Vs) and end-diastolic flow velocity (Vd) compare with the control group(P

Objective: To investigate the effects of Shenfu Injection (参附注射液, SFI) on endothelial damage in a porcine model of hemorrhagic shock (HS). Methods: After being bled to a mean arterial pressure of 40±3 mm Hg and held for 60 min, 32 pigs were treated with a venous injection of either shed blood (transfusion group), shed blood and saline (saline group), shed blood and SFI (SFI group) or without resuscitation (sham group). Venous blood samples were collected and analyzed at baseline and 0, 1, 2, 4, and 6 h after HS. Tumor necrosis factor-α (TNF-α), serum interleuking (IL)-6, and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA); expressions of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM -1), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and Bcl-2, Bax, and caspase-3 proteins were determined by Western blot. Results: The serum level of TNF-α in the SFI group was significantly lower than in the other groups at 0, 1, and 2 h after HS, while the level of IL-6 was lower at 4 and 6 h compared with the saline group (P<0.01 or P<0.05). The concentration of serum IL-10 was significantly higher in the SFI group than in the other groups at 0, 1, 4, and 6 h after HS (P<0.01). Western blot and immunohistochemistry of vascular tissue showed that the expression of caspase-3 was downregulated, and that of Bcl-2 and Bax was upregulated in the SFI group compared to other groups (P<0.05). Conclusion: SFI attenuated endothelial injury in the porcine model of HS by inhibiting cell apoptosis, suppressing the formation of proinflammatory cytokines, and reducing endothelial activation. [ABSTRACT FROM AUTHOR]

Background: Although increasing clinical trials studying Shenfu injection (SFI) comprising panaxoside 0.8 mg/ml extracted from Panax ginseng C.A. Mey. and aconitine 0.1 mg/ml extracted from Aconitum carmichaeli Debeaux for elderly patients with severe pneumonia on biomarkers associated with COVID-19 progression are emerging, there is no evidence-based evaluation for the effect of SFI on elderly severe pneumonia. Objectives: To evaluate the effect of SFI on elderly patients with severe pneumonia providing hints for treating critical COVID-19, we conducted a systematic review and meta-analysis. Methods: Nine databases, namely, PubMed, EMBASE, Web of Science, Science Direct, Google Scholar, Wanfang, Chongqing VIP Database, CNKI, and SinoMed were used to search clinical trials reporting the effect of SFI as an adjuvant for elderly severe pneumonia on outcomes of interest. Primary outcomes were total effective rate, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mortality, and safety. Secondary outcomes were predictors associated with COVID-19 progression. Duplicated or irrelevant articles with unavailable data were excluded. Cochrane Collaboration’s tool was used to evaluate the risk of bias by two reviewers independently. All data were analyzed by Rev Man 5.4. Continuous variables were shown as weighted mean difference (WMD) or standard mean difference (SMD) with 95% confidence intervals (95% CI), whereas dichotomous data were calculated as the risk ratio (RR) with 95% CI. Results: We included 20 studies with 1, 909 participants, and the pooled data showed that compared with standard control, SFI could improve the total effective rate (RR = 1.25, 95% CI = 1.14–1.37, and n = 689), APACHE II score (WMD = −2.95, 95% CI = −3.35, −2.56, and n = 809), and predictors associated with COVID-19 progression (brain natriuretic peptide, creatine kinase, stroke volume, cardiac output, left ventricular ejection fraction, cardiac index, sE-selectin, von Willebrand factor, activated partial thromboplastin time, platelet counts, D-Dimer, procalcitonin, and WBC count). SFI may reduce mortality (RR = 0.52, 95% CI = 0.37–0.73, and n = 429) and safety concerns (RR = 0.29, 95% CI = 0.17–0.51, and n = 150) for elderly severe pneumonia. Conclusion: SFI as an adjuvant may improve the total effective rate, APACHE II score, gas exchange, and predictors associated with COVID-19 progression, reducing mortality and safety concerns for elderly patients with severe pneumonia. [ABSTRACT FROM AUTHOR]

Background: Shenfu Injection (SFI) has emerged as a prevalent therapeutic intervention in clinical practice for the management of acute pancreatitis (AP). The purpose of this research was to investigate and validate the potential mechanisms of SFI in the treatment of AP through network pharmacology., Methods: Network pharmacology was adopted to investigate the potential targets and mechanisms of SFI in the treatment of AP. Molecular docking was employed to evaluate the binding affinity between active components and targets. Single-cell transcriptome analysis was conducted to explore the cell types associated with SFI treatment in AP. In vitro and in vivo models of AP were induced by caerulein. The histopathological changes were observed by HE staining. Cell apoptosis was detected using flow cytometry and Tunel staining. Cell viability was assessed using CCK-8 assay. Western blot and ELISA were used to detect the protein expression and inflammatory cytokines, respectively., Results: A total of 104 SFI active components were obtained, of which 29 targeted 76 genes. After intersecting with 3370 AP-related genes, 42 SFI treatment AP potential targets were identified. Enrichment analysis revealed that these targets were associated with cell apoptosis, necroptosis, and multiple signal transduction pathways, such as p53, IL-17 and TNF signal pathways, etc. Molecular docking demonstrated that the active components of SFI had good binding affinity with the corresponding targets and the binding ability of NGF and aromadendrene was the strongest. Bioinformatics analysis revealed that SFI treatment in AP is associated with various cell types, including acinar cells, endothelial cells, T cells, dendritic cells, ductal cells, and mesenchymal cells. Furthermore, in vitro experiments demonstrated that SFI induces acinar cell apoptosis in a dose-dependent manner, accompanied by increased expression of cleaved-caspase3/caspase3 and cleaved-caspase8/caspase8 proteins, and inhibition of inflammatory cytokine (TNF-ɑ, IL-1β, and PTGS2) expression. In vivo experiments demonstrated that SFI improved histopathological alterations, reduces inflammation, and promotes apoptosis and the expression of cleaved-casp3 and cleaved-casp8 in AP rats., Conclusions: This study elucidated the multi-component, multi-target, and multi-cellular characteristics of SFI in the treatment of AP, and confirmed its mechanism of promoting acinar cell apoptosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

This study aimed to investigate the therapeutic effect of Shenfu Injection on mice with chronic heart failure(CHF) and its effect on macrophage polarization. C57BL/6J mice were randomly assigned to the normal and model groups. The CHF model was established by intraperitoneal injection of isoproterenol(ISO, 7.5 mg·kg~(-1), 28 d). The successful modeling was determined by asses-sing the cardiac function and N-terminal pro-brain natriuretic peptide(NT-proBNP). The modeled mice were randomly divided into the model group, Shenfu Injection group, and TAK-242 group, and were injected intraperitoneally with the corresponding drugs for 15 days. Cardiac function was evaluated using echocardiography. Hematoxylin-eosin(HE) staining was used to detect the pathomorphology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the values of serum NT-proBNP, interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), IL-10, and arginase 1(Arg-1). Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. Quantitative polymerase chain reaction(qPCR) and Western blot were used to detect the changes in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway-related mRNA and protein expressions. Compared with the normal group, mice in the model group had lower values of left ventricular ejection fraction(LVEF) and left ventricular fractional shorte-ning(LVFS), higher values of left ventricular internal diastolic end-diastolic(LVIDd), left ventricular internal diastolic end-systolic(LVIDs), NT-proBNP, TNF-α, and IL-6(P&lt;0.01); the number of macrophages increased in cardiac tissues(P&lt;0.05), and the values of M1-F4/80~+CD86~+ were increased(P&lt;0.01), while the values of M2-F4/80~+CD163~+ decreased(P&lt;0.05); the mRNA and protein expressions of TLR4, myeloid differentiation factor 88(MyD88), IκB kinase α(IKKα), and NF-κB p65 in myocardial tissues were significantly elevated(P&lt;0.05, P&lt;0.01). Compared with the model group, mice in the Shenfu Injection and TAK-242 groups showed elevated LVEF, LVFS, IL-10, and Arg-1 levels, and decreased LVIDd, LVIDs, NT-proBNP, TNF-α, and IL-6 levels(P&lt;0.05, P&lt;0.01); the cardiac F4/80~+CD11b~+(macrophage) and M1-F4/80~+ CD86~+ values were significantly down-regulated, while M2-F4/80~+CD163~+ values were increased(P&lt;0.05, P&lt;0.01); and the mRNA and protein expressions of TLR4, MyD88, IKKα, and NF-κB p65 in myocardial tissues were notably decreased(P&lt;0.05, P&lt;0.01). CHF mice have an imbalance of M1/M2 macrophage polarization, with M1-type macrophages predominating. Shenfu Injection promotes macrophage polarization towards M2, inhibits M1-type macrophage activation, and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.

OBJECTIVE: To probe into the effects of linazolamine combined with Shenfu injection intervention on serum tumor necrosis factor α (TNF-α), procalcitonin (PCT), hypersensitivity C-reactive protein (hs-CRP) levels and and acute physiological and chronic health evaluation Ⅱ (APACHE Ⅱ) score in patients with sepsis. METHODS: Totally 197 patients with sepsis admitted into Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine Hospital from Jan. 2019 in Jan. 2021 were selected for retrospectively analysis, which were divided into control group and observation group according to the admission time. The 98 patients in the control group were treated with linazolamine injection, while the 99 patients in the observation group was given linazolamine combined with Shenfu injection. Changes of TNF-α, PCT, hs-CRP levels and APACHE Ⅱ score before and after treatment were compared between two groups. RESULTS: The serum TNF-α, PCT, hs-CRP levels and APACHE Ⅱ score in the observation group were significantly lower than those of the control group,with statistically significant differences (P<0. 05). All the TNF-α, PCT, hs-CRP levels and APACHE Ⅱ score were independent risk factors affecting the prognosis of patients with sepsis (P<0. 05), the APACHE Ⅱ score was positively associated with TNF-α, PCT and hs-CRP expression (P <0. 05). CONCLUSIONS: All the TNF-α, PCT, hs-CRP expression and APACHE Ⅱ score were independent risk factors of patients with sepsis, and the treatment of linazolamine combined with Shenfu injection can improve the clinical efficacy. [ABSTRACT FROM AUTHOR]

Objective: To investigate and analyze the therapeutic effect of Shenfu injection combined with osimertinib in the treatment of patients with advanced EGFR-positive non-small cell lung cancer and its effect on the immune function of patients.Methods: A total of 96 EGFR mutation-positive advanced NSCLC patients admitted to our hospital from June 2018 to December 2020 were randomly divided into observation group of 50 cases and control group of 46 cases. The control group was given oral treatment with osimertinib, and the observation group Shenfu injection was given on the basis of the control group, and both groups were treated for 16 weeks. The clinical efficacy, immune function indicators and patient quality of life scores were compared between the two groups.Results: Before treatment, there was no significant difference in the levels of T lymphocyte subsets and EORCT-QLQ-C30 scores between the two groups（P>0.05）; After treatment, compared with the control group, the observation group patients’ treatment effectiveness, CD4+/CD8+ ratio, functional areas and overall health status scores were significantly increased, while the peripheral blood CD8+ level and symptom area scores were significantly reduced（P<0.05）. Conclusion: Shenfu injection combined with Ositinib in the treatment of patients with advanced EGFR-positive NSCLC can effectively improve the clinical treatment effect, improve the immune function of the patient and improve the quality of life of the patient, and it is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

Microcirculatory dysfunction is one of the main characteristics of sepsis. Shenfu Injection (SFI) as a traditional Chinese medicine is widely applied in clinical severe conditions. Recent studies have shown that SFI has the ability to ameliorate sepsis-induced inflammation and to improve microcirculation perfusion. This study aims to investigate the underlying mechanism of SFI for ameliorating sepsis-associated endothelial dysfunction and organ injury. Side-stream dark-field (SDF) imaging was used to monitor the sublingual microcirculation of septic patients treated with or without SFI. Septic mouse model was used to evaluate the effects of SFI in vivo. Metabolomics and transcriptomics were performed on endothelial cells to identify the underlying mechanism for SFI-related protective effect on endothelial cells. SFI effectively abolished the disturbance and loss of sublingual microcirculation in septic patients. Twenty septic shock patients with or without SFI administration were enrolled and the data showed that SFI significantly improved the levels of total vessel density (TVD), perfused vessel density (PVD), microvascular flow index (MFI), and the proportion of perfused vessels (PPV). The administration of SFI significantly decreased the elevated plasma levels of Angiopoietin-2 (Ang2) and Syndecan-1, which are biomarkers indicative of endothelial damage in sepsis patients. In the mouse septic model in vivo , SFI inhibited the upregulation of endothelial adhesion molecules and Ly6G + neutrophil infiltration while restored the expression of VE-Cadherin in the vasculature of the lung, kidney, and liver tissue. Additionally, SFI reduced the plasma levels of Ang2, Monocyte Chemoattractant Protein-1(MCP1), and Interleukin-6 (IL6), and alleviated liver and kidney injury in septic mice. Moreover, SFI significantly inhibited the inflammatory activation and increased permeability of endothelial cells induced by endotoxins in vitro. By performing metabolomics and transcriptomics, we identified the activation of PI3K/Akt-mediated glycolysis as the underlying mechanism for SFI-related protective effect on endothelial cells. Our findings revealed that SFI may improve microcirculation perfusion and endothelial function in sepsis via inhibiting PI3K/Akt-mediated glycolysis, providing theoretical evidence for the clinical application of SFI. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Levosimendan can improve clinical symptoms and the cardiorenal rescue success rate, and stabilize hemodynamic parameters in individuals suffering from acute decompensated heart failure. In addition, Shenfu injection (SFI) has been shown to protect the ischemic heart and enhance myocardial contractility.Methods: For this randomized control single-blind study, 101 patients with acute decompensated heart failure (ADHF) were enrolled and randomly assigned to control levosimendan (n = 51) and levosimendan + SFI injection (n = 50) groups. Attending physicians were not blinded for which arm the patients were allocated. Blood pressure, heart rate, the electrocardiogram, respiratory rate, fluid intake and urine output were all recorded 2 h and 24 h after drug infusions had commenced, and the cardiac index (CI) was monitored by ultrasonic cardiac output monitors.Results: Median blood pressure was markedly increased in the levosimendan + SFI group after 2 h and 24 h from the initiation of infusions compared to levosimendan administration alone. Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P < 0.001). Alterations in BNP concentrations were not different in the combination and control groups. No differences were found between the 2 groups in heart rate or severe hypotension, but blood pressure (systolic blood pressure, diastolic blood pressure) and hemodynamic parameters including CI, cardiac output and stroke volume index responded better in the levosimendan + SFI group compared to the monotherapy levosimendan group.Conclusions: Levosimendan + SFI was superior to treat ADHF patients compared to levosimendan monotherapy and produced significant improvements in hemodynamic parameters especially for ADHF patients with hypotension. Trail registration The study was prospectively registered at Chinese Clinical Trial Registry with registration number [ChiCTR2000039385] (10/25/2020). [ABSTRACT FROM AUTHOR]

Objective: Shenfu injection (SFI) has been reported to have a protection against myocardial ischemia-reperfusion (MI/R) injury. However, the changes of adenosine receptors in MI/R postconditioning when pretreated with SFI are unclear. Methods: Forty-five rats were randomly divided into sham group (sham), MI/R postconditioning group (MI/R-post), low-dose SFI group (1 mL/kg), middle-dose SFI group (2.5 mL/kg), and high-dose SFI group (5 mL/kg). In SFI groups, SFI was intravenously injected before reperfusion, and rats were treated with ischemic postconditioning after ischemia for 30 min. After 24 h of reperfusion, the levels of Ca2+ and cAMP in blood platelets were analyzed. Myocardial infarct volume and myocardial pathology were observed. The levels of adenosine receptor subtypes A1, A2b, and A3 in myocardium were analyzed using immunohistochemistry and Western blot. The oxidative stress–related indicators were also observed. Results: Compared with the MI/R-post group, SFI ameliorated the MI/R injury by decreasing the myocardial infarct area, oxidative stress, and concentration of Ca2+ and cAMP (p < 0.01). Pretreatment with SFI enhanced the expression of adenosine receptors A1 and A2b in a dose manner compared with the MI/R-post group. In contrast, the levels of adenosine receptor A3 were increased after MI/R postconditioning compared with the sham group, and its expression continued to increase with the increase of SFI. Furthermore, the oxidative stress reduced with the concentrations of SFI. Conclusion: These results demonstrated that pretreatment with SFI might regulate the expression of adenosine receptors to improve the MI/R postconditioning. [ABSTRACT FROM AUTHOR]

Background: Shenfu injection is a traditional Chinese medicine formulation that alleviates ischemia-reperfusion injury through multiple pharmacologic effects. However, no data are available regarding its efficacy in patients with myocardial infarction. We aimed to examine the effects of Shenfu injection on infarct size in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods: From April 2016 to February 2018, 40 patients with first-time anterior STEMI undergoing primary PCI within 6 h of symptom onset were randomized 1:1 to intravenous Shenfu injection (80 ml Shenfu injection + 70 ml 5% glucose injection) or placebo (150 ml 5% glucose injection) before reperfusion. Treatment started before PCI and maintained for 5 days after PCI. The primary end point was infarct size assessed by CK-MB area under the curve (AUC) over 72 h and cardiac magnetic resonance (CMR) imaging 4 ± 1 days after PCI.Results: Infarct size by area under the curve for CK-MB over 72 h did not differ between the Shenfu injection and placebo groups (5602.5 [3539.4–7526.4] vs. 6403.2 [2234.4–8340.6] ng·h/ml, P = 0.82). Among 32 patients who underwent CMR Imaging, a nominal reduction in infarct size was observed in the Shenfu injection group compared with the placebo group (23.9 [15.2–28.5] % vs. 27 [21.9–31.9] %, P = 0.42). After excluding patients with no or minimal infarct, there was a trend toward reduction in infarct size in the Shenfu injection group (24.1 [20.3–29.3] % vs. 29.1 [24.5–32] %, P = 0.18). Incidence of adverse events was similar between the groups.Conclusions: This pilot study showed that the use of Shenfu injection was safe but did not reduce infarct size by CMR Imaging and CK-MB release kinetics in reperfused patients with STEMI. Larger studies (confining to patients with extensive infarct size) to evaluate the efficacy of Shenfu injection on reperfusion injury are warranted.Clinical Trail Registration:clinicaltrials.gov, identifier: NCT02709798.

Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The "gut-heart" axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5 mg kg -1 ·d -1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating co-metabolism and regulating the TMAO-inflammation axis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Ye, Zhao, Hu, Liang, Ouyang and Hu.)

Background: Shenfu (SF) injection, a traditional Chinese medication, would improve microcirculation in cardiogenic shock and infectious shock. This study was aimed to explore the therapeutic potential of the SF injection in gut ischemia-reperfusion (I/R) injury after severe hemorrhagic shock (SHS) and resuscitation. Furthermore, we also investigated the optimal adm？ inistration timing., Methods: Twenty-four male SD rats were randomly divided into four groups: Sham group (sham, n = 6), Control group (n = 6), SF injection group (SF, n = 6), and Delayed Shenfu injection administration group (SF-delay, n = 6). In SHS and resuscitation model, rats were induced by blood draw to a mean arterial pressure (MAP) of 40 ± 5 mmHg within 1 h and then maintained for 40 min; HR, MAP 'were recorded, microcirculation index [De Backer score, perfused small vessel density (PSVD), total vessel density (TVD), microcirculation flow index score (MFI), flow heterogeneity index (HI)] were analyzed. The blood gas index was detected, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), diamine oxidase (DAO), malondialdehyde (MDA) were measured by ELISA; ZO-1, and claudin-1 were measured by Western blotting. In addition, hematoxylin-eosin (HE) and periodic acid schiff (PAS) staining pathological sections of the intestinal mucosal tissues were also performed., Results: SF injection increased the MAP, relieved the metabolic acidosis degree associated with the hypoperfusion, and improved the intestinal microcirculatory density and perfusion quality after I/R injury. The expression of DAO, MDA in intestinal tissue, and plasma IL-6, TNF-α significantly decreased in the SF injection group compared to the control group. The concentration of ZO-1 and claudin-1 is also higher in the SF injection group. In addition, the HE and PAS staining results also showed that SF injection could decrease mucosal damage and maintain the structure. In the SF-delay group, the degree of intestinal tissue damage was intermediate between that of the control group and SF injection group., Conclusions: SF injection protect the intestine from I/R injury induced by SHS and resuscitation, the mechanism of which might be through improving intestinal microcirculation, reducing the excessive release of inflammatory factors and increasing intestinal mucosal permeability. Furthermore, the protection effect is more pronounced if administration during the initial resuscitation phase., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Shenfu injection was derived from the classical Chinese medicine formula 'Shenfu decoction', which was widely used in the treatment of cardiovascular and cerebrovascular diseases in clinical practice., Objectives: Predict the main active ingredients, core targets, and related signaling pathways of Shenfu injection in the treatment of ischemic stroke., Methods: Databases were used to collect the active ingredients and target information of Shenfu injection; GO and KEGG pathway enrichment analyses were performed using the David database. The effects of Shenfu injection on core targets were verified using molecular docking and in vivo experiments., Results: The predicted results identified 44 active ingredients and 635 targets in Shenfu injection, among which 418 targets, including TNF, IL-6, MAPK1, and MAPK14, were potential targets for the treatment of ischemic stroke. Molecular docking revealed that the active ingredients had good binding to IL-6, MAPK1, and MAPK14. In vivo experiments demonstrated that Shenfu injection significantly improved the pathological damage due to ischemic stroke, promoted the expression of tight junction proteins, and inhibited MMP-2 and MMP-9 expressions, thereby reducing BBB permeability. Animal experiments revealed that Shenfu injection could inhibit p38、JNK and ERK phosphorylation., Conclusions: Mechanism of Shenfu injection in treating ischemic stroke may be via inhibition of the inflammatory factors levels and protecting the BBB, thereby warranting subsequent studies and highlighting its potential as a reference for new drug development., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion., Method: This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization., Results: A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P =0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days-6.0 days vs . median=5.0 days, IQR: 3.0 days-8.0 days, respectively; P =0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3-2.0 mmol/L vs . median=0.0 mmol/L, IQR: -0.2 to 0.8 mmol/L, respectively; P <0.001) and 24 h (median=1.4 mmol/L, IQR: 0.3-2.2 mmol/L vs . median=0.4 mmol/L, IQR: -0.4 to 1.6 mmol/L, respectively; P =0.001)., Conclusion: SFI plus standard therapy did not significantly decrease 28-day all-cause mortality for septic patients with hypoperfusion and TCM syndrome with Yang-Qi deficiency. Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR1800020435., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Medical Association.)

Background: Idiopathic pulmonary fibrosis (IPF) is disease with high mortality, and its effective treatment is limited. Shenfu injection is a traditional Chinese medicine which can improve circulation and protect cells. In this study, we aimed to investigate the feasibility and mechanism of Shenfu injection in the treatment of IPF. Methods: The components and targets of Shenfu injection were mainly retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The targets of Shenfu injection were standardized by UniProt database. The Genecards and OMIM databases was used to search for IPF-related genes. The Venn diagram of gene intersection was drawn using the OmicStudio tools, and the protein-protein interaction network was visualized using the Cytoscape 3.7.2 software. Moreover, the metascape online software was applied to explore the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the Cytoscape 3.7.2 software was used to construct the target-pathway network. Molecular docking was used to visualize the interactions between the main active compounds and targeted proteins. Animal experiments were performed to validate the effects and mechanisms of Shenfu injection. Results: We obtained 46 co-targets of Shenfu injection and IPF. Among the hub target genes, several genes with important functions were enriched, including TNF, IL-6, IL-1B, TP53, JUN, CASP3 and CASP8. The pathway enrichment analysis for the hub target genes identified pathways in infection/inflammation, apoptosis and cancer. Molecular docking results showed that the main active compound Ginsenoside Re had high affinity to the core target proteins. These results suggested that Shenfu injection may have a positive effect in the treatment of IPF. Consistent with this finding, animal experiments showed that Shenfu injection significantly reduced pulmonary fibrosis in a mouse model with inhibition of apoptosis and inflammation by downregulating IL-1β, caspase-3 and phosphorylated NF-κB. Conclusion: Our results demonstrated that Shenfu injection efficiently alleviate bleomycin-induced pulmonary fibrosis through multi-targets in inflammation-, apoptosis- and cancer-related pathways, which provided first evidence and reference to the feasibility of Shenfu injection in the treatment of IPF. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is disease with high mortality, and its effective treatment is limited. Shenfu injection is a traditional Chinese medicine which can improve circulation and protect cells. In this study, we aimed to investigate the feasibility and mechanism of Shenfu injection in the treatment of IPF.Methods: The components and targets of Shenfu injection were mainly retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The targets of Shenfu injection were standardized by UniProt database. The Genecards and OMIM databases was used to search for IPF-related genes. The Venn diagram of gene intersection was drawn using the OmicStudio tools, and the protein-protein interaction network was visualized using the Cytoscape 3.7.2 software. Moreover, the metascape online software was applied to explore the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and the Cytoscape 3.7.2 software was used to construct the target-pathway network. Molecular docking was used to visualize the interactions between the main active compounds and targeted proteins. Animal experiments were performed to validate the effects and mechanisms of Shenfu injection.Results: We obtained 46 co-targets of Shenfu injection and IPF. Among the hub target genes, several genes with important functions were enriched, including TNF, IL-6, IL-1B, TP53, JUN, CASP3 and CASP8. The pathway enrichment analysis for the hub target genes identified pathways in infection/inflammation, apoptosis and cancer. Molecular docking results showed that the main active compound Ginsenoside Re had high affinity to the core target proteins. These results suggested that Shenfu injection may have a positive effect in the treatment of IPF. Consistent with this finding, animal experiments showed that Shenfu injection significantly reduced pulmonary fibrosis in a mouse model with inhibition of apoptosis and inflammation by downregulating IL-1β, caspase-3 and phosphorylated NF-κB.Conclusion: Our results demonstrated that Shenfu injection efficiently alleviate bleomycin-induced pulmonary fibrosis through multi-targets in inflammation-, apoptosis- and cancer-related pathways, which provided first evidence and reference to the feasibility of Shenfu injection in the treatment of IPF.

BACKGROUND: Shenfu injection (SFI) is a traditional Chinese herbal medicine which has been clinically used for treatment of septic shock and cardiac shock. The aim of this study was to clarify effects of SFI on cerebral microcirculation and brain injury after hemorrhagic shock (HS). METHODS: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n = 8), saline group (SA, n = 8) or sham operation group (SO, n = 5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40±3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin-6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured. RESULTS: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin-6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group. CONCLUSIONS: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether Shenfu Injection (SFI, 参附注射液) 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. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Based on the rapid health technology assessment(HTA),to evaluate the efficacy,safety and economical efficiency of Shenfu injection in the treatment of cardiac failure, so as to provide evidence-based evidence for clinical rational drug application. METHODS: HTA reports, systematic reviews/ Meta-analyses and pharmacoeconomic studies on Shenfu injection in the treatment of cardiac failure were involved by overall retrieving CNKI,Wanfang database,CBM,EMBase,PubMed and the Cochrane Library,qualitative description was adopted to conduct analysis and summary on the involved studies,and quality evaluation on the literature and its methodology were performed. RESULTS: Totally 14 studies were involved,13 of which were systematic reviews/ Meta-analyses,1 was pharmacoeconomic study,no HTA report was retrieved. The analysis result indicated that the combination of Shenfu injection and western conventional therapy in the treatment of cardiac failure had obvious advantages in promoting clinical effective rate, improving TCM syndrome score, reducing brain natriuretic peptide level, improving left ventricular ejection fraction, increasing cardiac output, improving heart pump function, reduce N-terminal B-type pronatriuretic peptide level, promoting 6-min walking distance, improving left ventricular shortening fraction and reducing readmission rate of patients with cardiac failure; however, the research conclusions on reducing the left ventricular end diastolic diameter and mortality were inconsistent; meanwhile, no obvious adverse drug reactions [ABSTRACT FROM AUTHOR]

Shenfu injection(SFI), as a famous classical Chinese patent medicine injection for the treatment of sepsis, has achieved good curative effects in clinical practice. However, its specific ingredients and molecular mechanisms is still unclear. To analyze the effective ingredients and molecular mechanisms of SFI in the treatment of sepsis via network pharmacology technology and experimental validation. A total of 198 mice were used in this experiment. Septic mice model was performed by cecal ligation and puncture (CLP). First, Survival rates were calculted to screen the dosage and the treatment time window of SFI. Cardiac function was evaluated by echocardiography. The potential targets and pathways of SFI in the treatment of sepsis were predicted by network pharmacology. Myocardial tissue samples were harvest from different groups after CLP surgery. Hematoxylin-eosin (H&E) and TUNEL staining were used to examine the injury of heart. Western-blot analysis was performed to determine the protein expression of apoptosis. Meanwhile, the structural changes and mitochondrial membrane potential in the mitochondria of cardiomyocytes were also observed by transmission electron microscopy. The Kaplan-Meier survival analysis showed that SFI significantly improved the 7-day survival rate as compared with that of CLP mice (P < 0.05). Echocardiography analysis found that LVEF and FS were significantly reduced in CLP mice compared with Sham mice, while SFI significantly increased LVEF (P < 001). Network pharmacology analysis indicated that the potential targets with higher degrees include IL2, BCL2, BAX, CASP7, BID, CASP8. Pathways with higher degrees include apoptosis, TNF signaling pathway, mitochondrial pathway apoptosis, PI3K-AKT signaling pathway. SFI treatment markedly attenuated the quantity of apoptotic cells as compared with the CLP group (P < 0.01). Western blot analysis indicated that CLP surgery decreased the expression of Bcl-2 (anti-apoptotic) but improved the protein expression of Bid, t-Bid, Cyc (pro-apoptotic) as compared with the Sham group (P < 0.01). While, SFI treatment markedly prevent the expression of Bid, t-Bid, Cyc and Caspase-9. The myocardial mitochondrial membrane potential of CLP group decreased after CLP surgery, while the mitochondrial membrane potential of SFI group increased significantly. Compared with the CLP group, in SFI group, the Z-line of the sarcomere was clear and distinguishable, and swollen mitochondria were significantly improved. The present study demonstrated that SFI improved survival rate and cardiac function of septic mice mainly by suppressing inflammation and apoptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Objectives This study aims to determine the protection provided by Shenfu injection (a traditional Chinese medicine) against development of organ dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19). Trial design This study is a multicenter, randomized, controlled, open-label, two-arm ratio 1:1, parallel group clinical trial. Participants The patients, who are aged from 18 to 75 years old, with a confirmed or suspected diagnosis of severe or critical COVID-19, will be consecutively recruited in the study, according to the guideline on diagnosis and treatment of COVID-19 (the 7th version) issued by National Health Commission of the People’s Republic of China. Exclusion criteria include pregnant and breastfeeding women, atopy or allergies to Shenfu Injection (SFI), severe underlying disease (malignant tumor with multiple metastases, uncontrolled hemopathy, cachexia, severe malnutrition, HIV), active bleeding, obstructive pneumonia caused by lung tumor, severe pulmonary interstitial fibrosis, alveolar proteinosis and allergic alveolitis, continuous use of immunosuppressive drugs in last 6 months, organ transplantation, expected death within 48 hours, the patients considered unsuitable for this study by researchers. The study is conducted in 11 ICUs of designated hospitals for COVID-19, located in 5 cities of China. Intervention and comparator The enrolled patients will randomly receive 100 ml SFI (study group) or identical volume of saline (control group) twice a day for seven consecutive days. Patients in the both groups will be given usual care and the necessary supportive therapies as recommended by the latest edition of the management guidelines for COVID-19 (the 7th version so far). Main outcomes The primary endpoint is a composite of newly developed or exacerbated organ dysfunction. This is defined as an increase in the sequential organ failure assessment (SOFA) score of two or more, indicating sepsis and involvement of at least one organ. The SOFA score will be measured for the 14 days after enrolment from the baseline (the score at randomization). The secondary endpoints are shown below: • SOFA score in total • Pneumonia severity index score • Dosage of vasoactive drugs • Ventilation free days within 28 days • Length of stay in intensive care unit • Total hospital costs to treat the patient • 28-day mortality • The incidence of adverse drug events related to SFI Randomisation The block randomization codes were generated by SAS V.9.1 for allocation of participants in this study. The ratio of random distribution is 1:1. The sealed envelope method is used for allocation concealment. Blinding (masking) The patients and statistical personnel analyzing study data are both blinded. The blinding of group assignment is not adopted for the medical staff. Numbers to be randomised (sample size) This study is expected to recruit 300 patients with COVID-19, (150 in each group). Trial Status Protocol version 2.0, February 15, 2020. Patient recruitment started on February 25, and will end on August 31, 2020. Trial registration Chinese Clinical Trial Registry: ChiCTR2000030043. Registered February 21, 2020, http://www.chictr.org.cn/showprojen.aspx?proj=49866 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Shenfu injection (SFI), composed of ginseng and aconite, is a Chinese patent developed from the classic traditional prescription Shenfu Decoction created more than 700 years ago. SFI has been widely used in China for over 30 years for treating cardiovascular diseases. The main components in it include ginsenosides and aconitum alkaloids. In recent years, the role of SFI in the treatment of cardiovascular diseases has attracted much attention. The pharmacological effects and therapeutic applications of SFI in cardiovascular diseases are summarized here, highlighting pharmacological features and potential mechanisms developments, confirming that SFI can play a role in multiple ways and is a promising drug for treating cardiovascular diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Xie, Hu, Tong and Peng.)

BackgroundGiven the severity of pulmonary heart disease and the wide utilization of Chinese herbal injections, this network meta-analysis was devised to assess the comparative efficacy of seven Chinese herbal injections (Ciwujia injection, Dazhuhongjingtan injection, Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, and Shenqi Fuzheng injection) that were combined with Western medicines in the treatment of pulmonary heart disease.MethodsA literature search was performed in PubMed, Cochrane Library, EMBASE, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang Database, and the Chinese Scientific Journal Database from their inception to July14, 2019. This network meta-analysis was conducted in accordance with a priori eligibility criteria and methodological quality recommendations. Data analysis was performed with WinBUGS 1.4.3 and Stata 13.0 software focusing on clinical effectiveness rate, arterial blood gas analysis, hemorheology and hemodynamic indexes and right ventricular dimensions. In addition to the odds ratio or mean difference in various outcomes, the ranking probability of interventions calculated by the surface under the cumulative ranking area curve was demonstrated. The surface under the cumulative ranking area was equal to the rank of the intervention and was aimed to assess the best intervention.ResultsUltimately, 118 randomized controlled trials including 10,085 patients were included. Integrating the outcome results, all eligible Chinese herbal injections plus Western medicines were superior to Western medicines alone, especially Shenfu injection+ Western medicines, Shenmai injection+ Western medicines, and Shenqi Fuzheng injection+ Western medicines. Regarding safety, the drip rate was an essential element for clinicians to consider during treatment.ConclusionsIn conclusion, Shenfu injection+ Western medicines, Shenmai injection+ Western medicines and Shenqi Fuzheng injection+ Western medicines may be potential optimal treatments for pulmonary heart disease. A larger sample size and high-quality randomized controlled trials are needed to confirm and support this network meta-analysis.

Vasomotor dysfunction is one of the key pathological aspects of shock and heart failure (HF). Shenfu injection (SFI) has been widely used for the treatment of shock and HF in China. Pharmacological studies have suggested that SFI can reduce peripheral circulation resistance and improve microcirculation. However, whether it has a regulatory effect on macrovascular has not been elucidated. In this study, we used thoracic aorta rings isolated from Wistar rats and the human umbilical vein cell line (EA.hy926) to explore the vasodilative activity of SFI and its potential mechanisms. The relaxation due to SFI was measured after pre-treatment with selective soluble guanylate cyclase (sGC) inhibitor or cyclooxygenase (COX) inhibitor and compared with the vasodilation effect of SFI only treated with norepinephrine (NE). The contents of NO, endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), COX-1, 6-K-PGF1α, and caveolin-1 were evaluated respectively. Additionally, the level of eNOS mRNA and total eNOS and its phosphorylation were studied to investigate the potential mechanisms involved. Experimental results showed that SFI markedly attenuated NE-induced vasoconstriction but that this effect was significantly eliminated after pre-incubation with the selective sGC inhibitor 1-H-[1, 2, 4] oxadiazolo [4, 3-α] quinoxaline-1-one (ODQ), instead of the COX inhibitor indomethacin (INDO). SFI significantly increased the eNOS content and up-regulated the eNOS mRNA expression, while it did not affect the content of COX-1 and 6-K-PGF1α. SFI also markedly increased NO content but significantly reduced the content of ET-1 and caveolin-1 in the cell supernatant. Furthermore, it promoted the expression of total eNOS and the phosphorylation of eNOS at serine (Ser) 1177 but inhibited the phosphorylation at threonine (Thr) 495, which was significantly reversed by PI3K-specific inhibitor LY294002. In conclusion, our study showed the vasodilation effect of SFI in thoracic aorta is mediated entirely by enhancing eNOS activity through the PI3K/Akt signaling pathway, providing novel knowledge on the effect of SFI on shock and HF for future clinical applications.

Objectives: We aimed to evaluate the effect of Shenfu injection in a rat model of ischemic heart failure and explore its mechanism.Methods: A rat model of ischemic heart failure after myocardial infarction was established by ligating the left anterior descending coronary artery. Forty-eight hours after surgery, the rats were intraperitoneally administered Shenfu injection for 7 weeks. Then, left ventricular fractional shortening and left ventricular ejection fraction were measured using transthoracic echocardiography, whereas heart rate and left ventricular end-diastolic pressure were measured using a MD3000 biosignal acquisition and processing system. The hearts and lungs of the rats were excised and weighed to measure the heart and lung weight indexes. In addition, cardiac histopathological changes were observed via hematoxylin–eosin and Masson’s trichrome staining, and serum cardiac troponin content was detected using a cardiac troponin ELISA kit. Furthermore, matrix-assisted laser desorption/ionization–mass spectrometry imaging was used to detect the levels and distribution of small molecules in the hearts of rats with ischemic heart failure.Results: We found that Shenfu injection can significantly increase left ventricular fractional shortening and left ventricular ejection fraction in rats with ischemic heart failure and significantly reduce the left ventricular end-diastolic pressure, heart and lung weight indexes, and cardiac troponin content; improve cardiac tissue morphology; and reduce infarct size. In addition, the matrix-assisted laser desorption/ionization–mass spectrometry imaging results demonstrated that 22:6 phospholipids were predominately distributed in the non-infarct zone, whereas 20:4 phospholipids tended to concentrate in the infarct zone. Shenfu injection significantly reduced taurine, glutathione, and phospholipids levels in the hearts of rats with ischemic heart failure and primarily changed the distribution of these molecules in the non-infarct zone.Conclusion: Shenfu injection induced obvious myocardial protective effects in rats with ischemic heart failure by stimulating antioxidation and changing the phospholipid levels and distribution.

Background: Given the severity of pulmonary heart disease and the wide utilization of Chinese herbal injections, this network meta-analysis was devised to assess the comparative efficacy of seven Chinese herbal injections (Ciwujia injection, Dazhuhongjingtan injection, Huangqi injection, Shenfu injection, Shengmai injection, Shenmai injection, and Shenqi Fuzheng injection) that were combined with Western medicines in the treatment of pulmonary heart disease. Methods: A literature search was performed in PubMed, Cochrane Library, EMBASE, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Wanfang Database, and the Chinese Scientific Journal Database from their inception to July14, 2019. This network meta-analysis was conducted in accordance with a priori eligibility criteria and methodological quality recommendations. Data analysis was performed with WinBUGS 1.4.3 and Stata 13.0 software focusing on clinical effectiveness rate, arterial blood gas analysis, hemorheology and hemodynamic indexes and right ventricular dimensions. In addition to the odds ratio or mean difference in various outcomes, the ranking probability of interventions calculated by the surface under the cumulative ranking area curve was demonstrated. The surface under the cumulative ranking area was equal to the rank of the intervention and was aimed to assess the best intervention. Results: Ultimately, 118 randomized controlled trials including 10,085 patients were included. Integrating the outcome results, all eligible Chinese herbal injections plus Western medicines were superior to Western medicines alone, especially Shenfu injection+ Western medicines, Shenmai injection+ Western medicines, and Shenqi Fuzheng injection+ Western medicines. Regarding safety, the drip rate was an essential element for clinicians to consider during treatment. Conclusions: In conclusion, Shenfu injection+ Western medicines, Shenmai injection+ Western medicines and Shenqi Fuzheng injection+ Western medicines may be potential optimal treatments for pulmonary heart disease. A larger sample size and high-quality randomized controlled trials are needed to confirm and support this network meta-analysis. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess the effects of Shenfu injection (SFI) in combination with epinephrine during cardiac arrest on survival and neurological outcome after out-of-hospital cardiac arrest (OHCA).Methods: In this randomised, assessor-blind controlled trial, Utstein-style data were collected from 1233 OHCA patients treated at the Beijing Emergency Medical Center between January 2013 and June 2016. The patients were randomised into either a treatment group that received a combination of SFI and standard treatment with epinephrine or a control group that received standard treatment with epinephrine alone. The primary outcome was survival to hospital admission. The secondary outcomes were return of spontaneous circulation (ROSC), survival to hospital discharge, favourable neurological outcome at discharge, survival to one year, and favourable neurological outcome at one-year survival.Results: In both groups, the survival to hospital admission, ROSC, survival to hospital discharge, and one-year survival rate after discharge from the hospital did not differ significantly. However, SFI achieved favourable neurological outcome at discharge in comparison with the standard treatment with an odds ratio (OR) of 2.72 at a 95% confidence interval (CI; 1.00-8.53). Meanwhile, unlike with epinephrine alone, the combination of SFI and epinephrine achieved a better cerebral performance category (CPC) score (1-2) after one-year survival (OR: 5.08, 95% CI: 1.07-47.80).Conclusion: The combination of SFI and epinephrine had favourable neurological outcomes after OHCA compared with those with epinephrine alone, whereas the survival to admission was not significantly altered. [ABSTRACT FROM AUTHOR]

Shenfu injection (SFI), a Chinese medicinal product, shows potent efficacy in treating sepsis. The aim of the present study was to clarify the protective effects of SFI against lipopolysaccharide (LPS)-induced myocardial inflammation and apoptosis. Experiments were carried out in Sprague-Dawley (SD) rats treated with LPS or LPS + SFI, and in H9C2 cardiomyocytes. The sepsis-associated myocardial inflammation and apoptosis was induced by the intraperitoneal injection of LPS (20 mg·kg−1). SFI attenuated the increased expression of tumor necrosis factor (TNF)- α and interleukin (IL)-1 β induced by LPS both in serum and heart. In LPS group, cell viability was reduced, and reversed after SFI administration. LPS treatment increased the expression levels of cleaved-caspase 3 and Bax, and those of Bcl2 and Bcl2/Bax. These two trends were reversed by SFI administration. The expression levels of phosphorylated mitogen-activated protein kinase kinase (p-MEK) and phosphorylated extracellular regulated protein kinases (p-ERK) were increased by LPS, and reversed by SFI. MEK inhibitor U0126 attenuated the apoptosis induced by LPS. These results indicate that SFI could treat LPS-induced cardiac dysfunction. In conclusion, SFI attenuates the inflammation and apoptosis induced by LPS via downregulating the MEK and ERK signaling pathways. [ABSTRACT FROM AUTHOR]

Vasomotor dysfunction is one of the key pathological aspects of shock and heart failure (HF). Shenfu injection (SFI) has been widely used for the treatment of shock and HF in China. Pharmacological studies have suggested that SFI can reduce peripheral circulation resistance and improve microcirculation. However, whether it has a regulatory effect on macrovascular has not been elucidated. In this study, we used thoracic aorta rings isolated from Wistar rats and the human umbilical vein cell line (EA.hy926) to explore the vasodilative activity of SFI and its potential mechanisms. The relaxation due to SFI was measured after pre-treatment with selective soluble guanylate cyclase (sGC) inhibitor or cyclooxygenase (COX) inhibitor and compared with the vasodilation effect of SFI only treated with norepinephrine (NE). The contents of NO, endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), COX-1, 6-K-PGF1α, and caveolin-1 were evaluated respectively. Additionally, the level of eNOS mRNA and total eNOS and its phosphorylation were studied to investigate the potential mechanisms involved. Experimental results showed that SFI markedly attenuated NE-induced vasoconstriction but that this effect was significantly eliminated after pre-incubation with the selective sGC inhibitor 1-H-[1, 2, 4] oxadiazolo [4, 3-α] quinoxaline-1-one (ODQ), instead of the COX inhibitor indomethacin (INDO). SFI significantly increased the eNOS content and up-regulated the eNOS mRNA expression, while it did not affect the content of COX-1 and 6-K-PGF1α. SFI also markedly increased NO content but significantly reduced the content of ET-1 and caveolin-1 in the cell supernatant. Furthermore, it promoted the expression of total eNOS and the phosphorylation of eNOS at serine (Ser) 1177 but inhibited the phosphorylation at threonine (Thr) 495, which was significantly reversed by PI3K-specific inhibitor LY294002. In conclusion, our study showed the vasodilation effect of SFI in thoracic aorta is mediated entirely by enhancing eNOS activity through the PI3K/Akt signaling pathway, providing novel knowledge on the effect of SFI on shock and HF for future clinical applications. [ABSTRACT FROM AUTHOR]

Objective: To observe the influence of warm moxibustion on acupoints with a moxibustion box to change ratio of yang-deficiency constitution conversion fraction and change of serum ACTH content in people of yang deficiency constitution. Methods: 90 patients met the inclusion criteria and were randomly divided into the treatment group, the control group one and the control group two with 30 cases in each group. Patients in the treatment group were treated with therapy of warm moxibustion on acupoints with a moxibustion box. Patients in the control group one were given therapy of acupoint injection with Shenfu injection. Patients in the control group two were give oral administration of Jīn Guì Shèn Qì Wán (Golden Cabinet's Kidney Qi Pill, ...) for treatment. After consecutive treatment of 8 courses (55 days), the data compared change rate of yang-deficiency constitution conversion fraction and change of serum ACTH content. Results: After the treatment, yang-deficiency constitution conversion fraction of the three groups decreased, and the difference was statistically significant (P < 0.05) compared with that before the treatment. Comparison of change rate of yang-deficiency constitution conversion fraction between the three groups indicated that the differences were statistically significant (P < 0.05). The total consistent rate of judgment resulted in aspects of change of serum ACTH content and yang-deficiency constitution conversion fraction in three groups before and after the treatment was 91.1%, and the difference was not statistically significant (P > 0.05). After the treatment, total effective rate of the treatment group was higher than that of control group one and group two, and the differences were statistically significant (P < 0.05). Conclusions: All of the therapies; of warm moxibustion on acupoints with moxibustion box, acupoint injection with Shenfu injection and oral administration of Jīn Guì Shèn Qì Wán (Golden Cabinet's Kidney Qi Pill, ...) could improve yang deficiency constitution. However, the curative effect of warm moxibustion on acupoint with a moxibustion box was the best, which could be one of the optimizations of projects to improve yang deficiency constitution. In addition, its functional mechanism still needs further elaboration. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of Shenfu injection (SFI) combined with standard therapy versus standard therapy for septic shock, three groups of patients with septic shock were analyzed based on the level of mean arterial lactate. They were mean arterial lactate level < 4.5 mmol/L, 4.5 mmol/L ≤ mean arterial lactate level < 7 mmol/L and mean arterial lactate level ≥ 7 mmol/L.Methods: Randomized controlled trials (RCT) from PubMed, Cochrane library, Embase, CENTRAL, SinoMed, Wanfang, CNKI, and Weipu (VIP) databases from the inception to September 2018 were searched. Relative risks (RR), weighted mean difference (WMD), along with 95% confidence interval (95%CI) were used to analyze the main outcomes. Statistical analysis was performed using Rev.Man 5.3. The qualities of the involved studies were accessed by the ROB according to the Cochrane handbook.Results: 19 randomized controlled trials with 1505 participants were included. Compared with standard therapy, SFI plus standard therapy cannot decrease the 28-day mortality for all of the three groups. Compared with the other two subgroups (mean arterial lactate level < 4.5 mmol/L and mean arterial lactate level ≥ 7 mmol/L), the 4.5 mmol/L ≤ mean arterial lactate level < 7 mmol/L group has a trend to decrease 28-day mortality (RR: 0.67; 95% CI: 0.38-1.19; P = 0.17). In addition, adding SFI could have further increased mean arterial pressure (MAP) at 6-hours (RR: 7.05; 95% CI: 4.14-9.97) and further normalized heart rate (HR) when compared with standard therapy (RR: -17.48; 95% CI: [-19.39-(-15.57)].Conclusion: For septic shock patients with 4.5 mmol/L ≤ mean arterial lactate level < 7 mmol/L, when the Traditional Chinese Medicine syndrome meet Yang-Qi deficiency, clinicians could choose SFI as a supplementary drug. But further high-quality and large-scale RCT should be performed to verify it.Prospero Registration Number: CRD42018090320. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the effect of Shenfu injection in a rat model of ischemic heart failure and explore its mechanism. Methods: A rat model of ischemic heart failure after myocardial infarction was established by ligating the left anterior descending coronary artery. Forty-eight hours after surgery, the rats were intraperitoneally administered Shenfu injection for 7 weeks. Then, left ventricular fractional shortening and left ventricular ejection fraction were measured using transthoracic echocardiography, whereas heart rate and left ventricular end-diastolic pressure were measured using a MD3000 biosignal acquisition and processing system. The hearts and lungs of the rats were excised and weighed to measure the heart and lung weight indexes. In addition, cardiac histopathological changes were observed via hematoxylin–eosin and Masson's trichrome staining, and serum cardiac troponin content was detected using a cardiac troponin ELISA kit. Furthermore, matrix-assisted laser desorption/ionization–mass spectrometry imaging was used to detect the levels and distribution of small molecules in the hearts of rats with ischemic heart failure. Results: We found that Shenfu injection can significantly increase left ventricular fractional shortening and left ventricular ejection fraction in rats with ischemic heart failure and significantly reduce the left ventricular end-diastolic pressure, heart and lung weight indexes, and cardiac troponin content; improve cardiac tissue morphology; and reduce infarct size. In addition, the matrix-assisted laser desorption/ionization–mass spectrometry imaging results demonstrated that 22:6 phospholipids were predominately distributed in the non-infarct zone, whereas 20:4 phospholipids tended to concentrate in the infarct zone. Shenfu injection significantly reduced taurine, glutathione, and phospholipids levels in the hearts of rats with ischemic heart failure and primarily changed the distribution of these molecules in the non-infarct zone. Conclusion: Shenfu injection induced obvious myocardial protective effects in rats with ischemic heart failure by stimulating antioxidation and changing the phospholipid levels and distribution. [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical effect and security of shenfu injection combined with docetaxel in the treatment of advanced non-small cell lung cancer. Methods: 60 patients with non-small cell lung cancer were selected from January 2016 to January 2019 in our hospital and divided into two groups according to the random number table method, 30 cases in each group. Patients in the control group were given docetaxel injection for chemotherapy, and those in the observation group were given shenfu injection on the basis of those in the control group. The clinical effect after treatment, changes in immuno-function related indicators, life quality score before and after treatment and adverse reactions were compared between the two groups. Results: After treatment, the disease control rate was 86.67% in the observation group and 60.00% in the control group, which was significantly higher than that in the control group (P<0.05). After treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in the control group were significantly decreased, and the levels of CD8+ were significantly increased. The levels of CD3+, CD4+ and CD4+/CD8+ in the observation group were significantly increased, and the levels of CD8+ were significantly decreased. The levels of CD3+, CD4+ and CD4+/CD8+ in the observation group were significantly higher than those in the control group, and the levels of CD8+ were significantly lower than those in the control group (P<0.05). The scores of appetite, pain, fatigue, dyspnea, bloody sputum and cough in the two groups after treatment were significantly lower than those before treatment, and the above indexes in the observation group were significantly lower than those in the control group (P<0.05). The incidence of neutropenia and constipation in the observation group was significantly lower than that in the control group (P<0.05), and there was no statistical difference in the incidence of thrombocytopenia, nausea and vomiting and neurotoxicity between the two groups (P>0.05). Conclusion: Shenfu injection combined with docetaxel can significantly improve the immune function and quality of life of patients with advanced non-small cell lung cancer, improve the clinical treatment effect, and have high safety. [ABSTRACT FROM AUTHOR]