The Potential of Glycyrrhizinate in the Management of COVID-19: A Systematic Review of the Efficacy and Safety of Glycyrrhizin Preparations in the Treatment of SARS and MERS.

The SARS-CoV-2 outbreak in 2019 highlighted the fact that no specific medications providing effective treatment have been identified and approved. We explored the possibilities for COVID-19 by systematically reviewing evidence on the efficacy and safety of glycyrrhizin preparations for SARS and MERS. Electronic databases were systematically searched from inception to February 2020 for eligible studies that evaluated the efficacy and safety of glycyrrhizin preparations for SARS and MERS. A quantitative analysis or descriptive analysis was applied. Five retrospective cohort studies were included, and NOS scores ranged from 5-7 points. The clinical symptoms of dry cough, chest distress and dyspnoea improved quickly, and elevated serum levels of aminotransferase decreased after compound glycyrrhizin treatment. The SARS-CoV antibody appeared earlier in the treated group than in the control group ([Formula: see text][Formula: see text]d). Compared to that with conventional medications, the average period from peak to 50% improvement of lesions, in terms of X-ray manifestations, was shorter with compound glycyrrhizin treatment ([Formula: see text]2.1[Formula: see text]d), and treatment reduced the dosage ([Formula: see text][Formula: see text]mg/d) and duration of the corticosteroids used, without other serious adverse reactions. Based on the available evidence regarding glycyrrhizin preparations for treating SARS and MERS, we infer that compound glycyrrhizin could be an optional therapeutic strategy for SARS-CoV-2 infections, especially those complicated with liver damage. Further research using well-designed randomized clinical trials (RCTs) is warranted to determine the dosage and duration of use of compound glycyrrhizin and to monitor its specific adverse effects.

An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone.

Kurarinone is a major component found in the dried roots of Sophora flavescens Ait. that participates in vital pharmacological activities. Recombinant CYP450 supersomes and liver microsomes were used to study the metabolic profiles of kurarinone and its inhibitory actions against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes. 100 µM of kurarinone strongly inhibited more than 90% of UGT1A1, UGT1A6, CYP1A2, and CYP2C9. CYP1A2 and CYP2D6 played important roles in catalyzing the biotransformation of kurarinone. Moreover, metabolism of kurarinone considerably differs among species, and metabolic characteristics were similar between monkey and human. Kurarinone demonstrated moderate permeability at values of pH 4.0 and 7.4. Our findings offer a clearer idea to understand the pharmacological and toxicological mechanisms of kurarinone.

Association between the AUC0-24/MIC Ratio of Vancomycin and Its Clinical Effectiveness: A Systematic Review and Meta-Analysis.

BACKGROUND: A target AUC0-24/MIC ratio of 400 has been associated with its clinical success when treating Staphylococcus aureus infections but is not currently supported by state-of-the-art evidence-based research. OBJECTIVE: This current systematic review aimed to evaluate the available evidence for the association between the AUC0-24/MIC ratio of vancomycin and its clinical effectiveness on hospitalized patients and to confirm the existing target value of 400. METHODS: PubMed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were systematically searched. Manual searching was also applied. Both RCTs and observational studies comparing the clinical outcomes of high AUC0-24/MIC groups versus low AUC0-24/MIC groups were eligible. Two reviewers independently extracted the data. The primary outcomes were mortality and infection treatment failure. Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated. RESULTS: No RCTs were retrieved. Nine cohort studies were included in the meta-analysis. Mortality rates were significantly lower in high AUC0-24/MIC groups (RR = 0.47, 95%CI = 0.31-0.70, p<0.001). The rates of infection treatment failure were also significantly lower in high AUC/MIC groups and were consistent after correcting for heterogeneity (RR = 0.39, 95%CI = 0.28-0.55, p = 0.001). Subgroup analyses showed that results were consistent whether MIC values were determined by broth microdilution (BMD) method or Etest method. In studies using the BMD method, breakpoints of AUC0-24/MIC all fell within 85% to 115% of 400. CONCLUSIONS: This meta-analysis demonstrated that achieving a high AUC0-24/MIC of vancomycin could significantly decrease mortality rates by 53% and rates of infection treatment failure by 61%, with 400 being a reasonable target.

Comparative study between original and traditional method in establishing a chronic sinus node damage model in rabbit.

Sick Sinus Syndrome is a common and refractory arrhythmia, needing further study in which setting up a credible sinus node damage model is important. To explore the feasibility and superiority of an original formaldehyde pinpoint pressing permeation (FPPP) method for building a chronic sinus node damage (CSND) model, 5 rabbits were chosen from 35 as a sham-operation group, and the remaining were randomly divided into two groups: the formaldehyde wet compressing (FWC) group, in which models were established by applying a cotton bud dipped in 20% formaldehyde onto the sinus node (SN) area, and the FPPP group, in which models were established by injecting formaldehyde into the SN area through a self-made pinpointing and injecting electrode. We found that in both groups, the HR at 2 h, 24 h, 1 wk, and 2 wk after modeling decreased compared with premodeling; sinoatrial conduction time, sinus node recovery time, and corrected sinus node recovery time were prolonged compared with premodeling. The indexes mentioned shortened by 2 wk after modeling compared with 2 h in the FWC group, whereas they were stable after modeling in the FPPP group. The modeling achievement ratio in the FPPP group was higher and the death rate was lower. Under light microscope, paraffin sections of the SN tissue and cells showed severe injury in both groups. The results indicate that the CSND models in rabbits can be successfully established by the FPPP method, with higher achievement ratio, lower death rate, better stabilization effect, and less damaging comparing with the traditional method.

[Effect of kangxin fulu recipe on electrophysiological functions of the sinoatrial node in rabbits with sick sinus syndrome].

OBJECTIVE: To study the effect of Kangxin Fulu Recipe (KFR) on electrophysiological functions of the sinoatrial node in rabbits with sick sinus syndrome (SSS). METHODS: Sixty big ears white rabbits were randomly divided into six groups, i.e., the normal group, the model group, the atropine group, the high dose KFR group, the middle dose KFR group, and the low dose KFR group, ten in each group. SSS model was established by injecting formaldehyde to the sinoatrial node except those in the normal group. Changes in AA interval, the sinoatrial conduction time (SACT), the sinus node recovery time (SNRT), and the corrected sinus node recovery time (CSNRT) were measured before and after modeling, seven days before and after gastrogavage. RESULTS: (1) The AA interval and SACT could be significantly shortened in the high dose KFR group, the middle-dose KFR group, and the atropine group (P<0.05, P<0.01). Better effects were obtained in the former two groups (P<0.05). (2) SNRT and CSNRT could be shortened in the high dose KFR group and the atropine group, with no statistical difference between the two groups (P>0.05). CONCLUSION: The electrophysiological mechanism of KFR might possibly be correlated with accelerating the recovery of sinus node autorhythmicity and conduction functions.