Efficacy and safety of Qi and Blood Tonic Chinese Medicines in the treatment of COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease in 2019 (COVID-19) is a sudden public event affecting all human beings, with the rapid transmission, extensive groups affected, many complications, and high mortality. Traditional Chinese Medicine has a long history of preventing and treating infectious diseases, and numerous studies have shown that Traditional Chinese Medicine, especially herbal medicine, has a positive effect on the prevention, treatment, and post-healing recovery of this COVID-19, and herbal medicines to supplement qi and blood often occupy a certain proportion of it. However, there is no relevant meta-analysis to date. Therefore, this study aims to evaluate the efficacy and safety of qi and blood tonic herbal medicines in the treatment of COVID-19 through Systematic Review and meta-analysis to provide a reference basis for widespread clinical application. METHODS: We will search from the following databases for the period from the time of database construction to March 1st, 2023. The English databases include: PubMed, MEDLINE, EMBASE, Cochrane library, WOS, Google Scholar, and CENTRAL; The Chinese databases include: China National Knowledge Infrastructure, China Biomedical Literature Database, Technology Journal Database, and Wanfang. Randomized controlled trials in English or Chinese that include Chinese herbal medicines for tonifying Qi and Blood in the treatment of patients with COVID-19 will be included. Data were independently screened and collected by 2 investigators. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.3 software was used for the meta-analysis of the data. Primary outcome indicators included cure, mortality, and exacerbation rates (change in disease severity category, patient admission to ICU, etc.). Secondary outcome indicators included recovery rate or duration of major symptoms (e.g., fever, cough, fatigue, and weakness, etc.), rate or duration of nucleic acid conversion for severe acute respiratory syndrome coronavirus-2, improvement or recovery of chest CT performance, length of hospital stay, and other adverse events. RESULTS: This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-P guidelines to ensure clarity and completeness of reporting in all phases of the systematic review. CONCLUSION: This study will provide evidence regarding the efficacy and safety of Qi and Blood Tonic Chinese Medicines for the treatment of COVID-19. PROSPERO REGISTRATION NUMBER: CRD42022361822 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361822).

Mechanism of Datura metel on sinus bradycardia based on network pharmacology and molecular docking.

OBJECTIVE: To investigate the mechanism of action of Datura metel in the treatment of sinus bradycardia based on network pharmacology and molecular docking. METHODS: The active ingredients and targets of Datura metel were collected by TCMSP database, and the Cytoscape software was used to map to show the interrelationship. Use 5 databases: GeneCards, PharmGKB, OMIM, DisGeNET, and Drugbank to obtain targets related to sinus bradycardia; establish a protein-to-protein interaction network with the help of the STRING platform; GO and Kyoto Encyclopedia of Genes and Genomes analysis of the selected core targets using the Metascape platform; Finally, the AutoDock platform was used for molecular docking and the results were displayed through Pymol. RESULTS: 27 kinds of active ingredients of the drug were screened, including 10 kinds of main ingredients; 198 drug targets and 1059 disease targets. There are 54 targets of action in the treatment of sinus bradycardia, of which 19 targets such as AKT1, IL6, TNF, and VEGFA are the core targets of Datura metel in the treatment of sinus bradycardia. Kyoto Encyclopedia of Genes and Genomes obtained 18 results suggesting that AGE-RAGE, hepatitis C, relaxin, and JAK-STAT may be key signaling pathways. Molecular docking shows that most components of the drug have good docking ability with the core target, indicating that the prediction results have certain reliability. CONCLUSION: This study preliminarily explores the potential active ingredients and possible mechanisms of action of Datura metel in the treatment of sinus bradycardia and provides a basis for in-depth investigation of its medicinal material basis and mechanism of action.

[Effect of Xinling Wan in treatment of stable angina pectoris: a randomized, double-blinded, placebo parallel-controlled, multicenter trial].

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.

Sodium Hydroxide Pinpoint Pressing Permeation Method for the Animal Modeling of Sick Sinus Syndrome.

Sodium hydroxide pinpoint pressing permeation (SHPPP) was investigated in order to build a rat model of sick sinus syndrome (SSS), which is easy to operate and control the degree of damage, with fewer complications and applicable for large and small animals.Thirty healthy Wistar rats (15 males and 15 females, weighing 250-350 g) were randomly divided into 3 groups, namely a formaldehyde thoracotomy wet compressing group (FTWC), formaldehyde pinpoint pressing permeation group (FPPP) group, and SHPPP group. The number of surviving rats, heart rate (HR), sinoatrial node recovery time (SNRT), corrected SNRT (CSNRT), and sinoatrial conduction time (SACT) were recorded 3 days, one week, and two weeks after modeling.The achievement ratio of modeling was 10% in the FTWC group, 40% in the FPPP group, and 70% in the SHPPP group, and the differences were statistically significant (χ(2) = 7.250, P = 0.007). Meanwhile, the HR was reduced by about 37% in these 3 groups 3 days after modeling, while the reduction was maintained only in SHPPP (P > 0.05) and the HR was re-elevated in the FTWC and FPPP groups 2 weeks after modeling (P < 0.05). Additionally, the SNRT, cS-NRT, and SACT were significantly prolonged compared with pre-modeling in all 3 groups (P < 0.01).SHPPP was the best method with which to build an SSS model with stable and lasting low HR and high success rate of modeling, which might be helpful for further studies on the SSS mechanisms and drugs.

Metabolomic profiling for identification of potential biomarkers in the protective effects of modified Sinisan against liver injury in dimethylnitrosamine treated rats.

Metabolomics is a new platform based on the comprehensive analysis of low molecular weight metabolites and provides a powerful approach to discover biomarkers in biological systems. Modified Sinisan (MSNS), a traditional Chinese medicine formula, displayed bright prospects in the prevention and therapy of liver injury. However, its molecular mechanism of hepatoprotective effects remains unclear. This paper was designed to explore the effects and potential mechanisms of MSNS against dimethylnitrosamine-induced liver injury. Global metabolic profiling was performed by ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-Q-TOF-MS) in conjunction with multivariate data analysis and pathway analysis. Eleven serum biomarkers were identified and pathway analysis results showed that phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, tryptophan metabolism, retinol metabolism, tyrosine metabolism were perturbed by liver injury. More importantly, MSNS has showed satisfactory pharmacological effect on liver injury through partially regulating the perturbed pathways, correlates well to the biochemical and histopathological detection results. The present study proved that the robust metabolomics approach is promising for unraveling hepatoprotective effects of MSNS and these findings provide new insights into mechanisms of the liver injury, and its pathophysiologic processes.