An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: a nonrandomized controlled trial
- Shengjing Hospital of China Medical University, China
- Dalian University of Technology, China
- China Resources Sanjiu Medical and Pharmaceutical Co, Ltd, China
- Peking University, China
- Shanghai BeautMed Corporation, China
- University of Copenhagen, Denmark
Abstract
Background: Plasma cell mastitis (PCM) is a nonbacterial breast inflammation with severe and intense clinical manifestation yet treatment methods for PCM are still rather limited. Although the mechanism of PCM remains unclear, mounting evidences suggest that the dysregulation of immune system is closely associated with the pathogenesis of PCM. Drug combinations or combination therapy could exert improved efficacy and reduced toxicity through hitting multiple discrete cellular targets.
Methods: We have developed a knowledge graph architecture towards immunotherapy and systematic immunity that consists of herbal drug-target interactions with a novel scoring system to select drug combinations based on target-hitting rates and phenotype relativeness. To this end, we employed this knowledge graph to identify an herbal drug combination for PCM and we subsequently evaluated the efficacy of the herbal drug combination in clinical trial.
Results: Our clinical data suggests that the herbal drug combination could significantly reduce the serum level of various inflammatory cytokines, downregulate serum IgA and IgG level, reduce the recurrence rate and reverse the clinical symptoms of PCM patients with improvements of general health status.
Conclusions: In summary, we reported that an herbal drug combination identified by knowledge graph can alleviate the clinical symptoms of plasma cell mastitis patients. We demonstrated that the herbal drug combination holds great promise as an effective remedy for PCM, acting through the regulation of immunoinflammatory pathways and improvement of systematic immune level. In particular, the herbal drug combination could significantly reduce the recurrence rate of PCM, a major obstacle for PCM treatment. Our data suggests that the herbal drug combination is expected to feature prominently in future PCM treatment.
Funding: Liu's lab was supported by grants from the Public Health Science and Technology Project of Shenyang (Grant: 22-321-32-18), Y. Yang's laboratory was supported by the National Natural Science Foundation of China (Grant: 81874301); the Fundamental Research Funds for Central University (Grant: DUT22YG122) and the Key Research project of 'be Recruited and be in Command' in Liaoning Province (2021JH1/10400050).
Clinical trial number: ClinicalTrials.gov: NCT05530226.
Data availability
Figure 1-3 are computational study and therefore no data have been generated for the manuscript. In addition, Figure 4 - Source Data, Figure 5 - Source Data, Figure 6 - Source Data 1, Figure 6 - Source Data 2 and Figure 6 - Source Data 3 contain the numerical data used to generate the figures have been included in the manuscript.
Article and author information
Author details
Funding
National Natural Science Foundation of China (81874301)
- Yongliang Yang
National Natural Science Foundation of China (81572609)
- Caigang Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The protocol was approved by the Institutional Review Board (IRB) of the China Medical University (approval number: 2021PS024T). This study was registered with ClinicalTrials.gov: NCT05530226. All patients provided written informed consent.
Copyright
© 2023, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: a nonrandomized controlled trial
eLife 12:e84414.
https://doi.org/10.7554/eLife.84414
Further reading
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- Microbiology and Infectious Disease
Background:
Under which conditions antibiotic combination therapy decelerates rather than accelerates resistance evolution is not well understood. We examined the effect of combining antibiotics on within-patient resistance development across various bacterial pathogens and antibiotics.
Methods:
We searched CENTRAL, EMBASE, and PubMed for (quasi)-randomised controlled trials (RCTs) published from database inception to 24 November 2022. Trials comparing antibiotic treatments with different numbers of antibiotics were included. Patients were considered to have acquired resistance if, at the follow-up culture, a resistant bacterium (as defined by the study authors) was detected that had not been present in the baseline culture. We combined results using a random effects model and performed meta-regression and stratified analyses. The trials’ risk of bias was assessed with the Cochrane tool.
Results:
42 trials were eligible and 29, including 5054 patients, qualified for statistical analysis. In most trials, resistance development was not the primary outcome and studies lacked power. The combined odds ratio for the acquisition of resistance comparing the group with the higher number of antibiotics with the comparison group was 1.23 (95% CI 0.68–2.25), with substantial between-study heterogeneity (I2=77%). We identified tentative evidence for potential beneficial or detrimental effects of antibiotic combination therapy for specific pathogens or medical conditions.
Conclusions:
The evidence for combining a higher number of antibiotics compared to fewer from RCTs is scarce and overall compatible with both benefit or harm. Trials powered to detect differences in resistance development or well-designed observational studies are required to clarify the impact of combination therapy on resistance.
Funding:
Support from the Swiss National Science Foundation (grant 310030B_176401 (SB, BS, CW), grant 32FP30-174281 (ME), grant 324730_207957 (RDK)) and from the National Institute of Allergy and Infectious Diseases (NIAID, cooperative agreement AI069924 (ME)) is gratefully acknowledged.
