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Background: Heart failure with reduced ejection fraction (HFrEF) is a complex, chronic disease and is among the top causes of morbidity and mortality. Angiotensin receptor-neprilysin inhibitor drugs represented by sacubitril/valsartan are the key drugs for the treatment of HFrEF in western medicine, and Qili Qiangxin Capsule (QQC) is a vital drug for the treatment of HFrEF in Chinese medicine. In recent years, there have been many relevant clinical studies on the combination of the two in the treatment of HFrEF. There are no systematic reviews or meta-analyses specific to sacubitril/valsartan combined with QQC for the treatment of HFrEF, so there is an urgent need to evaluate the effectiveness and safety of these two drugs. Objective: To systematically assess the safety and effectiveness of QQC combined with sacubitril/valsartan in the treatment of HFrEF through a meta-analysis. Methods: Searching studies on the combination of QQC and sacubitril/valsartan in the treatment of HFrEF, from databases such as PubMed, Cochrane Library, Web of Science, Wanfang Databases, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure, prior to 31 October 2021. Two reviewers regulated research selection, data extraction, and risk of bias assessment. Review Manager Software 5.4 was used for meta-analysis. Results: There were 26 studies with 2,427 patients included in total. The meta-analysis showed the combination therapy has significant advantages in improving the clinical efficacy, 6-MWT (RR = 1.18, 95% CI: 1.11–1.26, MD = 70.65, 95% CI: 23.92–117.39), superior in ameliorating LVEF, LVEDD, LVESD, and SV (LVEF: MD = 5.41, 95% CI: 4.74–6.08; LVEDD: MD = −4.41, 95% CI: −6.19 to −2.64; LVESD: MD = −3.56, 95% CI: −4.58 to −2.54; and SV: MD = 5.04, 95% CI: 3.67–6.40), and in improving BNP, NT-proBNP, AngII, and ALD (BNP: MD = −97.55, 95% CI: −112.79 to −82.31; NT-proBNP: MD = −277.22, 95% CI: −348.44 to −206.01; AngII: MD = −11.48, 95% CI: −15.21 to −7.76; and ALD: MD = −26.03, 95% CI: −38.91 to −13.15), and all the differences have statistical advantages (p < 0.05). There are no advantages in improving CO and adverse events (MD = 0.66, 95% CI: −0.12 to 1.43 and RR = 0.62, 95% CI: 0.37–1.04, respectively), and the differences have no statistical advantages. Conclusion: Compared with the control group, QQC combined with sacubitril/valsartan may be effective in the treatment of HFrEF. However, the conclusion of this study must be interpreted carefully due to the high risk and ambiguity of bias in the included trials. [ABSTRACT FROM AUTHOR]

Psycho-cardiological disease refers to the presence of somatic cardiovascular symptoms associated with negative emotions, with or without cardiovascular disease. Cogntion is the whole process of the brains receiving and processing of external information, from which cognitive psychology is developed and has become an important component of modern psychology research ; its core content is to emphasize the negative mood plays a key role in the development of emotional disorders, and provides a new perspective for the understanding of psycho-cardiological disease. The theory of Traditional Chinese medicine holds that the heart is closely related to the cognitive process. The epistemic process is highly summarized in the 8th chapter of Basic state of Spirit (benshen) in Miraculous Pivot (Lingshu) as "perception, memory, mind, volition, thinking, consideration and wisdom". As the heart is the chief of all the organs, it not only controls the blood vessels and consciousness, but also dominate other organs. The heart leads the sensory organs to perform the function of "perception", completes the process of "memory, mind, volition, thinking and consideration" by regulating the kidney, spleen and liver, and finally integrates all the information to determine the result of "wisdom", which makes a systematic connection between the heart, cognition and emotion. Based on this, we put forward the principle of calming the mind as the main treatment, supplemented by invigorating qi and promoting blood circulation, strengtliening spleen and reducing phlegm, regulating liver and qi, communicating heart and kidney. This paper adds to the scientific connotation of psycho-cardiological disease and simultaneous heart-brain tretment. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effectiveness and safety of Chinese herbal medicine (CHM) for the treatment of aspirin resistance (AR). Methods: A comprehensive research of seven electronic databases was performed for comparative studies evaluating CHM for AR. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data wasere synthesized by using RevMan 5.3 software. (PROSPERO Registration #CRD42015020182) Results: 18 randomized controlled trials (RCTs) involving 1,460 patients were included. 15 RCTs reported significant difference in the reduction of platelet aggregation rate (PAR) induced by adenosine diphosphate (ADP) (P<0.05), and 11 reported significant effect of CHM plus aspirin to reduce PAR induced by arachidonic acid (AA) (P<0.05) compared with aspirin 100mg/d treatment. The pooling data of 3 RCTs showed the thromboxane B2 (TXB2) in patients with CHM plus aspirin versus aspirin were significantly reduced (Random Effect model (RE), Standard Deviation (SD) = -95.93, 95% Confidential Interval (CI)[-118.25,-73.61], P<0.00001). Subgroup analysis showed that TXB2 (Fixed Effect model (FE), SD = -89.23, 95%CI[-121.96,-56.49], P<0.00001) had significant difference in Tongxinluo capsule plus aspirin versus aspirin. 2 RCTs reported the clinical effective rate, and the meta-analysis result showed a significant difference in intervention and control group (FE, Relative Risk (RR) = 1.67, 95%CI[1.15, 2.42], P = 0.007<0.05). In 4 trials, CHM plus aspirin had better effects of reducing the reoccurrence of cerebral infarction than aspirin (FE, RR = 0.24, 95%CI [0.11, 0.49], P<0.0001). And one trial showed that CHM plus aspirin could decrease the National Institutes of Health Stroke Scale (NHISS) score (P<0.05) and increase the Barthel Index (BI) score (P<0.05). 4 trials stated that there were no adverse effects occurred in intervention group, and analysis showed significant difference of CHM or CHM plus aspirin in reducing the occurrence of adverse events (FE, RR = 0.22, 95%CI[0.13, 0.39], P<0.00001). 5 trials claimed that the CHM monotherapy and CHM adjunctive therapy for AR did not add the risk of bleeding (FE, RR = 0.50, 95%CI[0.20, 1.22], P = 0.13>0.05). Conclusions: CHM may be effective and safe as an alternative and collaborative therapy for AR. However, the current evidence and potential promising findings should be interpreted with caution due to poor and varying methodological quality of included studies and the heterogeneity of interventions. Thus, further exploration of this strategy with adequately powered RCTs is warranted. [ABSTRACT FROM AUTHOR]

Jiawei Yanghe Decoction (JWYHD) is a widely used traditional Chinese medicine prescription in the clinical setting for the treatment of autoimmune diseases. Many studies showed that JWYHD has anti-tumor activities in cell and animal models. However, the anti-breast cancer effects of JWYHD and the underlying mechanisms of action remain unknown. This study aimed to determine the anti-breast cancer effect and reveal the underlying mechanisms of action i n vivo, in vitro and in silico. Orthotopic xenograft breast cancer mouse model and inflammatory zebrafish model were used to observe the anti-tumor effect and immune cell regulation of JWYHD. Moreover, the anti-inflammatory effect of JWYHD were evaluated by the expression of RAW 264.7 cells. JWYHD active ingredients were obtained by UPLC-MS/MS and potential targets were screened by network pharmacology. The therapeutic targets and signaling pathways predicted by computer were assessed by Western blot, real-time PCR (RT-PCR), immunohistochemistry (IHC) staining, and Enzyme-linked immunosorbent assays (ELISA) to explore the therapeutic mechanism of JWYHD against breast cancer. At last, Colivelin and Stattic were used to explore the effect of JWYHD on JAK2/STAT3 pathway. JWYHD significantly decreased the tumor growth in a dose-dependent manner in the orthotopic xenograft breast cancer mouse model. Flow cytometry and IHC results indicated that JWYHD decreased the expressions of M2 macrophages and Treg while increasing M1 macrophages. Meanwhile, ELISA and Western blot results showed a decrease in IL-1β, IL-6, TNFα, PTGS2 and VEGFα in tumor tissue of JWYHD groups. The results were also verified in LPS-induced RAW264.7 cells and zebrafish inflammatory models. TUNEL assay and IHC results showed that JWYHD significantly induced apoptosis. Seventy-two major compounds in JWYHD were identified by UPLC-MS/MS and Network pharmacology. It was found that the significant binding affinity of JWYHD to TNFα, PTGS2, EGFR, STAT3, VEGFα and their expressions were inhibited by JWYHD. IHC and Western blot analysis showed that JWYHD could decrease the expression of JAK2/STAT3 pathway. Furthermore, Colivelin could reverse the decrease effect of JWYHD in vitro. JWYHD exerts a significant anti-tumor effect mainly by inhibiting inflammation, activating immune responses and inducing apoptosis via the JAK2/STAT3 signaling pathway. Our findings provide strong pharmacological evidence for the clinical application of JWYHD in the management of breast cancer. JWYHD inhibited the release of inflammatory cytokines such as IL-1β, IL-6, TNFα, and PTGS2, promoted immune cell activation, and impaired tumor microenvironment in orthotopic xenograft breast cancer mouse model. JWYHD reduced the inflammatory responses and induced breast cancer cells apoptosis by inhibiting the activation of JAK2/STAT3 signaling pathway. [Display omitted] • Jiaweiyanghe Decoction (JWYHD) achieves significant anti-tumor activity in the orthotopic xenograft breast cancer mouse model. • JWYHD does not affect breast cancer cell proliferation in vitro. • JWYHD display a strong anti-inflammation effect both in vivo, in vitro and in silico. • Orthotopic xenograft mouse model and inflammatory zebrafish model were used in this experiment. • High-throughput and molecular docking are used to screen active components and immune-related potential targets in JWYHD. [ABSTRACT FROM AUTHOR]

Tanshinone IIA (TSA), the main lipo-soluble component from the dried rhizome of Salvia miltiorrhiza , has been shown to induce vasodilation. However, the underlying mechanisms remains unclear. This study aimed to investigate the effect of TSA on the vasodilation of small resistant arteries ex vivo. Vascular myography revealed that endothelial denudation reduced significantly the vasodilatory effect of TSA. Blocking transient receptor potential vanilloid 4 (TRPV4) channels prevented TSA-induced vasodilation. Whole-cell patch-clamp analysis revealed that the current passing through TRPV4 channels increased after TSA treatment in endothelial cells (ECs). This was attributed to reduced TRPV4 protein degradation along with its increased expression. The TRPV4 inhibitor HC-067047 lowed nitric oxide (NO) production and TSA-induced expression of endothelial nitric oxide synthase (eNOS). Moreover, it increased the production of cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG). The present results indicate that TSA induces endothelium-dependent vasodilation, which is mediated by the TRPV4-NO-PKG signaling pathway. These findings highlight the potential of TSA, a compound known in traditional Chinese medicine as Danshen (Salvia miltiorrhiza), for future cardiovascular therapeutic strategies. • Tanshinone IIA (TSA) shows potent vasodilatory effects on small resistant arteries, crucial for cardiovascular health. • Endothelial denudation significantly attenuates TSA-induced vasodilation, highlighting the pivotal role of endothelial cells. • TSA activates TRPV4 channels, increasing nitric oxide (NO) production via eNOS, which leads to vasodilation. • Blocking TRPV4 channels stops TSA-induced vasodilation, highlighting the TRPV4-NO-PKG signaling pathway's role. [ABSTRACT FROM AUTHOR]

The incidence of coronary heart disease (CHD) complicated with anxiety or depression is increasing year by year. However, many anti-anxiety drugs or antidepressants have a certain degree of adverse reactions and are not easily accepted by patients. Xinkeshu (XKS), as a proprietary Chinese patent medicine with "psycho-cardiology" effect, is one of the commonly used drugs in the treatment of CHD complicated with anxiety or depression in China. To systematically evaluate the efficacy and safety of XKS for CHD complicated with anxiety or depression. Nine different electronic databases were independently searched to include randomized controlled trials (RCTs) of XKS for CHD complicated with anxiety or depression published from inception to February 2022, and the methodological quality was evaluated using the bias risk assessment tool from Cochrane Handbook 5.0 and the modified Jadad scale. Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. The GRADE Profiler 3.6.1 and TSA 0.9.5.10 beta were adopted to evaluate the certainty and conclusiveness of the evidence. A total of 18 RCTs involving 1907 subjects were included. There were 956 subjects in the XKS group and 951 subjects in the control group. Baseline conditions were consistent and comparable between the groups. Compared with single-use western medicine (WM), XKS combined with WM significantly reduced scores of Hamilton Anxiety Scale (HAMA) [Mean difference (MD) = −7.60, 95% confidence interval (95% CI) (−10.37, −4.83), P < 0.000 01], Zung Self-rating Anxiety Scale (SAS) [MD = −10.05, 95% CI (−12.70, −7.41), P < 0.000 01], Hamilton Depression Scale (HAMD) [MD = −6.74, 95% CI (−11.58, −1.90), P = 0.006], and Zung Self-rating Depression Scale (SDS) [MD = −10.75, 95% CI (−17.05,-4.45), P = 0.000 8], as well as improved clinical effective rate [odds ratio (OR) = 4.24, 95% CI (2.47, 7.27), P < 0.000 01]. In terms of safety, 4 studies reported the adverse reactions in detail. The severity was mild and symptoms disappeared after treatment. Current evidence indicates that XKS may be effective and safe in the treatment of patients with CHD complicated with anxiety or depression. Since the quality of the literature included in this study was generally low, there is an urgent need for more RCTs with high quality, low bias risk and sufficient sample size to validate our conclusions. [Display omitted] [ABSTRACT FROM AUTHOR]

Zhenwu Decoction (ZWD) is a traditional Chinese medicine (TCM) formula which has wide scope of indications related to Yang deficiency and dampness retention in TCM syndrome. Cardiac hypertrophy can induce similar symptoms and signs to the clinical features of Yang deficiency and dampness retention syndrome. ZWD can increase the left ventricular ejection fraction, reduce cardiac hypertrophy of patients with chronic heart failure. However, its underlying pharmacological mechanism remains unclear. The study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms. The potential targets and pathways of ZWD in cardiac hypertrophy were highlighted by network pharmacology and validated by mechanistic and functional studies. Our network pharmacology analysis suggests that the protective effects of ZWD on cardiac hypertrophy are related to cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. Subsequent animal studies showed that ZWD significantly ameliorated cardiac function decline, cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. To explore the underlying mechanisms of action, we performed Western blotting, immunohistochemical analysis, and detection of inflammatory response and oxidative stress. Our results showed that ZWD activated the soluble guanylate cyclase (sGC) - cGMP - PKG signaling pathway. The sGC inhibitor ODQ that blocks the sGC-cGMP-PKG signaling pathway in zebrafish abolished the protective effects of ZWD, suggesting sGC-cGMP-PKG is the main signaling pathway mediates the protective effect of ZWD in cardiac hypertrophy. In addition, three major ingredients from ZWD, poricoic acid C, hederagenin and dehydrotumulosic acid, showed a high binding energy with prototype sGC. ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway. [Display omitted] • Zhenwu Decoction (ZWD) exhibited significant therapeutic effects on cardiac hypertrophy. • ZWD restored the sGC-cGMP-PKG signaling pathway suppressed by cardiac hypertrophy. • Inhibition of the sGC-cGMP-PKG signaling pathway abolished the protective effect of ZWD on cardiac hypertrophy. [ABSTRACT FROM AUTHOR]