Study on the Mechanism of Huanglian Jiedu Decoction in Treating Dyslipidemia Based on Network Pharmacology.

Objective: This study aimed to determine the active ingredients of Huanglian Jiedu decoction (HLJDD) and the targets for treating dyslipidemia through network pharmacology to facilitate further application of HJJDD in the treatment of dyslipidemia. Methods: Potential drug targets for dyslipidemia were identified with a protein-protein interaction network. Gene ontology (GO) enrichment analysis and KEGG pathway analysis were performed to elucidate the biological function and major pathways involved in the HLJDD-mediated treatment of dyslipidemia. Results: This approach revealed 22 components, 234 targets of HLJDD, and 221 targets of dyslipidemia. There were 14 components and 31 common targets between HLJDD and dyslipidemia treatment. GO enrichment analysis showed that these targets were mainly associated with the response to DNA-binding transcription factor activity, lipid localization and storage, reactive oxygen species metabolic process, and inflammatory response. The results of KEGG analysis indicated that the AGE-RAGE, NF-κB, HIF-1, IL-17, TNF, FoxO, and PPAR signalling pathways were enriched in the antidyslipidemic action of HLJDD. Conclusion: This study expounded the pharmacological actions and molecular mechanisms of HLJDD in treating dyslipidemia from a holistic perspective, which may provide a scientific basis for the clinical application of HLJDD.

Efficacy and safety of sitagliptin and insulin for latent autoimmune diabetes in adults: A systematic review and meta-analysis.

AIMS/INTRODUCTION: The optimal therapy for latent autoimmune diabetes in adults (LADA) remains undefined. Increasing evidence has shown that sitagliptin and insulin treatment can benefit patients with LADA, but the efficacy still lacks systematic evaluation. We carried out this systematic review and meta-analysis to summarize the current data on the efficacy and safety of sitagliptin combined with insulin on LADA, providing a reliable reference for the effective therapeutic treatment of LADA patients. MATERIALS AND METHODS: We retrieved the literature in PubMed, Cochrane Library, Embase, Web of Science and CNKI from inception to August 2021. Randomized controlled trials comparing the effects of sitagliptin plus insulin with insulin alone in LADA patients were identified. The outcome measures included parameters of glycemic control, ß-cell function, body mass index and adverse events. The Review Manager 5.2 and Stata 14.0 were utilized for data analysis. RESULTS: Eight randomized controlled trials involving 295 participants were identified. Sitagliptin and insulin treatment lowered hemoglobin A1c (weighted mean difference -0.36, 95% confidence interval -0.61 to -0.10, I2 = 91.6%), increased fasting C-peptide (weighted mean difference 0.08, 95% confidence interval -0.02 to 0.17, I2 = 88.8%) and had fewer adverse events compared with insulin alone. The inter-study heterogeneity, potential publication bias and other factors might interpret asymmetrical presentation of funnel plots. There was no significant association between sitagliptin plus insulin treatment and levels of hemoglobin A1c or fasting C-peptide, regardless of the duration of intervention and sample size. CONCLUSIONS: Sitagliptin combined with insulin can achieve better glycemic control and improve islet ß-cell function with lower incidence of hypoglycemia compared with insulin alone, which provides an effective and tolerated therapeutic regimen for LADA patients. However, further well-designed and rigorous randomized controlled trials are required to validate this benefit due to the limited methodology quality of included trials.

Effect of Shenfu Injection on Differentiation of Bone Marrow Mesenchymal Stem Cells into Pacemaker-Like Cells and Improvement of Pacing Function of Sinoatrial Node.

Sick sinus syndrome (SSS), a complex type of cardiac arrhythmia, is a major health threat to humans. Shenfu injection (SFI), a formula of traditional Chinese medicine (TCM), is effective in improving bradyarrhythmia. However, the underlying mechanism of SFI's therapeutic effect is subject to few systematic investigations. The purpose of the present research is to examine whether SFI can boost the differentiation effectiveness of bone marrow mesenchymal stem cells (BMSCs) into pacemaker-like cells and whether the transplantation of these cells can improve the pacing function of the sinoatrial node (SAN) in a rabbit model of SSS. BMSCs from New Zealand rabbits were extracted, followed by incubation in vitro. The flow cytometry was utilized to identify the expression of CD29, CD44, CD90, and CD105 surface markers. The isolated BMSCs were treated with SFI, and the whole-cell patch-clamp method was performed to detect hyperpolarization-the activated cyclic nucleotide-gated potassium channel 4 (HCN4) channel current activation curve. The SSS rabbit model was established using the formaldehyde wet dressing method, and BMSCs treated with SFI were transplanted into the SAN of the SSS rabbit model. We detected changes in the body-surface electrocardiogram and recorded dynamic heart rate measurements. Furthermore, transplanted SFI-treated BMSCs were subjected to HE staining, TUNEL staining, qPCR, western blotting, immunofluorescence, immunohistochemistry, and enzyme-linked immunosorbent assay to study their characteristics. Our results indicate that the transplantation of SFI-treated BMSCs into the SAN of SSS rabbits improved the pacing function of the SAN. In vitro data showed that SFI induced the proliferation of BMSCs, promoted their differentiation capacity into pacemaker-like cells, and increased the HCN4 expression in BMSCs. In vivo, the transplantation of SFI treated-BMSCs preserved the function of SAN in SSS rabbits, improved the expression of the HCN4 gene and gap junction proteins (Cx43 and Cx45), and significantly upregulated the expression of cAMP in the SAN, compared to the SSS model group. In summary, the present research demonstrated that SFI might enhance the differentiation capacity of BMSCs into pacemaker-like cells, hence offering a novel approach for the development of biological pacemakers. Additionally, we confirmed the effectiveness and safety of pacemaker-like cells differentiated from BMSCs in improving the pacing function of the SAN.

Effects of Home-Based Baduanjin Exercise on Left Ventricular Remodeling in Patients With Acute Anterior ST-Segment Elevation Myocardial Infarction: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) is a major pathological basis associated with heart failure and increased mortality. Exercise-based cardiac rehabilitation has been verified to significantly improve prognosis and quality of life. As a traditional Chinese Qigong, Baduanjin exercise has effectively alleviated adverse LV remodeling in STEMI patients. Despite this, participation in exercise rehabilitation remains low, and home-based exercise rehabilitation may be an alternative approach. Besides, anterior STEMI is reported to have higher risk of adverse LV remodeling. However, the efficiency regarding home-based Baduanjin exercise on LV remodeling in anterior STEMI patients remains uncertain currently. METHODS/DESIGN: A single-blind, randomized controlled clinical trial was conducted to explore the efficacy and safety of home-based Baduanjin exercise in anterior STEMI patients compared with moderate intensity aerobic walking. A total of 114 participants were assigned randomly to the Baduanjin group or walking control group at a 1:1 ratio. Eligible participants practiced Baduanjin or walking exercise (5 times a week) for 12 weeks, and then followed up for another 12 weeks. The primary outcome is a relative change in the LV end-diastolic volume. The secondary outcomes include the plasma levels of hypersensitive C-reactive protein and interleukin 6, health-related quality of life measured by EQ-5D-5L, LV ejection fraction, patient health questionnaire-9, generalized anxiety disorder screener-7, short physical performance battery score, and clinical endpoint events. The proportion of circulating regulatory T-cells were also assessed. Adverse events were recorded throughout the trial for safety evaluation. Data were be analyzed by researchers blinded to the treatment allocation. DISCUSSION: This study provided powerful evidence for the use of home-based Baduanjin exercise in anterior STEMI patients in alleviating LV remodeling and improving clinical outcomes. TRIAL REGISTRATION: The Research Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine has approved this study (ZYYECK[2020]045). Written informed consent of patients were required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2100047298). DISSEMINATION: Our results will be published in peer-reviewed journals and disseminated through academic conferences and the Internet.

Huang-Lian-Jie-Du Decoction Attenuates Atherosclerosis and Increases Plaque Stability in High-Fat Diet-Induced ApoE-/- Mice by Inhibiting M1 Macrophage Polarization and Promoting M2 Macrophage Polarization.

Macrophage polarization plays a vital impact in triggering atherosclerosis (AS) progression and regression. Huang-Lian-Jie-Du Decoction (HLJDD), a famous traditional Chinese decoction, displays notable anti-inflammatory and lipid-lowering effects in different animal models. However, its effects and mechanisms on AS have not been clearly defined. We determined whether HLJDD attenuated atherosclerosis and plaques vulnerability by regulating macrophage polarization in ApoE-/- mice induced by high-fat diet (HFD). Furthermore, we investigated the effects of HLJDD on macrophage polarization in oxidized low-density lipoprotein (ox-LDL) induced RAW264.7 cells. For in vivo assay, compared with the model group, HLJDD ameliorated lipid metabolism, with significantly decreased levels of serum triglyceride, total cholesterol (CHOL), and lipid density lipoprotein. HLJDD suppressed serum tumor necrosis factor α (TNF-α) and IL-1ß levels with increased serum IL-10 level, and inhibited mRNA level of NLRP3 inflammasome in carotid tissues. HLJDD enhanced carotid lesion stability by decreasing macrophage infiltration together with increased expression of collagen fibers and α-SMA. Moreover, HLJDD inhibited M1 macrophage polarization, which decreased the expression and mRNA levels of M1 markers [inducible nitric oxide synthase (iNOS) and CD86]. HLJDD enhanced alternatively activated macrophage (M2) activation, which increased the expression and mRNA levels of M2 markers (Arg-1 and CD163). For in vitro assay, HLJDD inhibited foam cell formation in RAW264.7 macrophages disturbed by ox-LDL. Besides, groups with ox-LDL plus HLJDD drug had a lower expression of CD86 and mRNA levels of iNOS, CD86, and IL-1ß, but higher expression of CD163 and mRNA levels of Arg-1, CD163, and IL-10 than ox-LDL group. Collectively, our results revealed that HLJDD alleviated atherosclerosis and promoted plaque stability by suppressing M1 polarization and enhancing M2 polarization.

Shen fu injection for patients with septic shock: Protocol for an updated systematic review.

BACKGROUND: Septic shock is a serious disease with high morbidity, which will lead to organ dysfunction. Shen fu injection (SFI) has been widely used for septic shock as a treatment in China. Many clinical trials have been reported that it could assess the efficacy and safety of SFI to cure septic shock and accelerate resuscitation. Reassessing the efficacy and safety of SFI as a treatment of patients with septic shock is the objective of this updated systematic review. METHODS: The following electronic databases major in English and Chinese will be conducted a systematic search until September 2018: PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Chinese BioMedical Literature Database, and Wan-fang Database. Randomized controlled trials of SFI will be included. Review Manager 5.2 software will be used for assessment of risk of bias, data synthesis, and subgroup analysis. We will conduct the GRADE system to assess the quality of evidence, if possible. RESULTS: This study will provide a rational synthesis of current evidences for SFI on septic shock. CONCLUSION: We hope our research results will provide an objective and reliable evidence to patients, clinicians and healthcare policymakers who are concerning the treatment options of SFI in septic shock. REGISTRATION: PROSPERO CRD42016049332.

Yixinshu capsule combined with conventional treatment for chronic heart failure: Protocol for a systematic review and trial sequential analysis.

BACKGROUND: Yixinshu Capsule is widely utilized in Asia for the treatment of chronic heart failure (CHF) as a conventional drug, but a comprehensive conclusion is lacking. Here, we will provide a protocol to perform a meta-analysis and trial sequential analysis to evaluate the efficacy of Yixinshu Capsule combined with conventional treatment for chronic heart failure. METHODS: We will conduct a thorough search in six databases, PubMed, EMBASE, Cochrane Library Database, Chinese National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and Chinese Biomedical and Medical Database (CBM). Inclusion criteria will be randomized control trials (RCTs) with one group receiving Yixinshu Capsule based on conventional treatment and another group receiving conventional treatment alone. Modified Jadad scale and Cochrane's risk of bias assessment will be used to assess methodological quality. Only studies with modified Jadad scale score ≥3 will be included in meta-analysis for efficacy, which will be defined as moderate methodological quality. The total effective rate will be considered as the primary outcome and the secondary outcome will include mortality, rehospitalized rate, left ventricular ejection fraction (LVEF), 6-minute walking distance, E/A, left ventricular end-diastolic diameter (LVEDD), BNP, and NT-proBNP. We will conduct trial sequential analysis to evaluate the reliability of the primary outcome. RESULTS: This study will provide a rational synthesis of current evidences for Yixinshu Capsule on chronic heart failure. CONCLUSION: The conclusion of this study will provide evidence for judging the efficacy of Yixinshu Capsule on chronic heart failure. REGISTRATION: PROS-PERO CRD42019119612.

Nuanxin capsule for heart failure: A systematic review of randomized controlled trials.

OBJECTIVE: To assess the efficacy and safety of Nuanxin capsule for patients with heart failure (HF). METHODS: A systematic literature search was performed in 6 databases: PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Wan-fang Data Information Site, Chinese BioMedical Database (CBM), VIP Chinese Science and Technique Journals Database from the date of its inception up to November 2016. Review Manager 5.2 software was used for assessment of risk of bias, data synthesis and subgroup analysis. Begg and Egger tests were used for assessing symmetries of funnel plot by software Stata 12.0. We conducted the GRADE system to assess the quality of evidence. RESULTS: 12 trials involving 1418 participants were eligible. Compared with western medicine (WM) alone, Nuanxin capsule plus WM showed statistical significance in total effective rate (RR 1.18, 95% condidence interval [CI] 1.13-1.25). According to subgroup analysis, the 6-months group and the 12-months group have better effect than the 3-month group. As for 6-minute walking distance (6MWT), Nuanxin capsule plus WM compared with WM has significantly increased walking distance (weighted mean difference [WMD] 42.56, 95% CI 34.27-50.85). Nuanxin capsule plus WM has significantly decreased in mortality (RR 0.29, 95% CI 0.18-0.46) and re-admission rate (RR 0.48, 95% CI 0.39-0.60) compared with WM. Nuanxin capsule plus WM was beneficial for B-type natriuretic peptide (-240.47, 95% CI -332.45-148.49). gger's and Begg's test showed that there was no publication bias exist (P = .937). Influence analysis showed that no single study affected the overall result. The GRADE quality of the evidence was very low to Moderate across the different outcomes. CONCLUSIONS: Despite of the apparently positive findings, we cannot draw a sound conclusion that Nuanxin capsule has positive effect in patients with HF, because of the insufficient evidence.

Baduanjin Exercise for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To investigate the effects of Baduanjin exercise for type 2 diabetes mellitus. METHODS: Literature retrieval was performed in several databases, including PubMed, EMBASE, Cochrane Library, CNKI, Wanfang Data Information Site, CBM, and VIP from inception to April 2017. Randomized controlled trials on evaluating the effects of Baduanjin exercise were identified. The primary outcomes were glycosylated hemoglobin, fasting blood-glucose, and postprandial plasma glucose. Review Manager 5.2 (RevMan 5.2) and Stata V.13.0 software were conducted for data analysis. RESULTS: The results of the meta-analysis indicated that the effects of type 2 diabetes mellitus were favoring Baduanjin plus conventional therapy, when compared with the routine treatment. Baduanjin plus conventional therapy lowered the level of glycosylated hemoglobin, fasting blood-glucose, postprandial plasma glucose, TC, TG, and LDL-C and improved HDL-C. Adverse events were not mentioned in all included studies. No publication bias was detected by Begg's and Egger's test and no single study affected the overall result by influence analysis. CONCLUSIONS: Evidence from meta-analysis suggested that Baduanjin exercise plus conventional therapy has a positive effect on type 2 diabetes mellitus. However, more rigorously designed and large sample RCTs are required to confirm the efficacy and safety in further studies.