An herbal drug combination identified by knowledge graph alleviates the clinical symptoms of plasma cell mastitis patients: A nonrandomized controlled trial
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eLife assessment
This study presents a useful identification of an herbal drug combination for the treatment of plasma cell mastitis (PCM), a breast inflammation with severe and intense clinical symptoms. The data were collected and analyzed using a solid and in clinical trial of 160 patients (NCT05530226) and can be used as a starting point for understanding how herbal drug combinations could be helpful in the management of PCM patients.
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Abstract
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 evidence suggests 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 by hitting multiple discrete cellular targets.
Methods:
We have developed a knowledge graph architecture toward 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 in general health status.
Conclusions:
In summary, we reported that an herbal drug combination identified by knowledge graph can alleviate the clinical symptoms of PCM 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 to PCM treatment. Our data suggests that the herbal drug combination is expected to feature prominently in future PCM treatment.
Funding:
C. 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:
NCT05530226 .
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Author Response
Reviewer #1 (Public Review):
This manuscript describes a relatively novel approach to discovering combinations of herbal medications that may help modulate immune responses, and in turn help treat diseases such as cancer. The authors use breast plasma call mastitis as a disease in which they present results from a non-blinded clinical trial with modest results. The main shortcomings are a lack of rigor around standardizing the control group given steroids versus the treatment group given the combinations of herbal medications. There needs to be a detailed statistical analysis of the comparison in tumor size, stage, invasiveness, etc. as well as consideration of confounding disease states (autoimmune disease, prior cancers, diabetes, etc.). While the results are interesting in that the use of herbal medications is …
Author Response
Reviewer #1 (Public Review):
This manuscript describes a relatively novel approach to discovering combinations of herbal medications that may help modulate immune responses, and in turn help treat diseases such as cancer. The authors use breast plasma call mastitis as a disease in which they present results from a non-blinded clinical trial with modest results. The main shortcomings are a lack of rigor around standardizing the control group given steroids versus the treatment group given the combinations of herbal medications. There needs to be a detailed statistical analysis of the comparison in tumor size, stage, invasiveness, etc. as well as consideration of confounding disease states (autoimmune disease, prior cancers, diabetes, etc.). While the results are interesting in that the use of herbal medications is often overlooked in Western medicine, the manuscript needs great detail in the clinical comparison in order to provide convincing evidence for an effect.
Many thanks for your very kind words about our work. We are excited to hear that you think our manuscript is relatively novel with considerable translational impact to the field of herbal medications. We are grateful for your valuable time and efforts you have spent to provide your very insightful comments, which are of great help for our revision.
Reviewer #2 (Public Review):
The work is rather interesting and novel because for the first time, the authors employed knowledge graph, a cutting-edge technique in the domain of artificial intelligence, to identify a novel herbal drug combination for the treatment of PCM. The results of the clinical trial study clearly demonstrated that the drug combination is effective to ameliorate the symptoms of PCM patients and improve the general health status of the patients. Overall, the strategy of this manuscript may provide a paradigm for the design of drug combination towards many other human disorders.
We are truly grateful for your very kind words about our work. It is very encouraging to know that you think our work is novel and of significance for the field. We sincerely appreciate the valuable time and kind efforts that you have spent on the thorough review of our manuscript.
Reviewer #3 (Public Review):
The major merit of the manuscript is that the authors introduced the concept of knowledge graph into the domain of herbal drugs or TCM. Namely, the authors designed a knowledge graph towards systematic immunity or immunotherapy based on massive data mining techniques. The authors successfully identified an herbal drug combination for PCM with the help of a scoring system. Moreover, the authors conducted a clinical trial study and the clinical data showed that the herbal drug combination holds great promise as an effective treatment for PCM. The weakness of the manuscript is that some details for the herbal drug combination and the clinical trial study are missing.
Many thanks for your very kind words about our work. We are excited to hear that you think our work is relatively novel and holds great promise as an effective remedy for PCM. We are truly thankful for your valuable time and efforts you have spent to provide your very insightful comments, which are of great help for our revision.
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eLife assessment
This study presents a useful identification of an herbal drug combination for the treatment of plasma cell mastitis (PCM), a breast inflammation with severe and intense clinical symptoms. The data were collected and analyzed using a solid and in clinical trial of 160 patients (NCT05530226) and can be used as a starting point for understanding how herbal drug combinations could be helpful in the management of PCM patients.
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Reviewer #1 (Public Review):
This manuscript describes a relatively novel approach to discovering combinations of herbal medications that may help modulate immune responses, and in turn help treat diseases such as cancer. The authors use breast plasma call mastitis as a disease in which they present results from a non-blinded clinical trial with modest results.
The main shortcomings are a lack of rigor around standardizing the control group given steroids versus the treatment group given the combinations of herbal medications. There needs to be a detailed statistical analysis of the comparison in tumor size, stage, invasiveness, etc. as well as consideration of confounding disease states (autoimmune disease, prior cancers, diabetes, etc.). While the results are interesting in that the use of herbal medications is often overlooked in …
Reviewer #1 (Public Review):
This manuscript describes a relatively novel approach to discovering combinations of herbal medications that may help modulate immune responses, and in turn help treat diseases such as cancer. The authors use breast plasma call mastitis as a disease in which they present results from a non-blinded clinical trial with modest results.
The main shortcomings are a lack of rigor around standardizing the control group given steroids versus the treatment group given the combinations of herbal medications. There needs to be a detailed statistical analysis of the comparison in tumor size, stage, invasiveness, etc. as well as consideration of confounding disease states (autoimmune disease, prior cancers, diabetes, etc.). While the results are interesting in that the use of herbal medications is often overlooked in Western medicine, the manuscript needs great detail in the clinical comparison in order to provide convincing evidence for an effect.
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Reviewer #2 (Public Review):
The work is rather interesting and novel because for the first time, the authors employed knowledge graph, a cutting-edge technique in the domain of artificial intelligence, to identify a novel herbal drug combination for the treatment of PCM. The results of the clinical trial study clearly demonstrated that the drug combination is effective to ameliorate the symptoms of PCM patients and improve the general health status of the patients. Overall, the strategy of this manuscript may provide a paradigm for the design of drug combination towards many other human disorders.
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Reviewer #3 (Public Review):
The manuscript presented the identification of an herbal drug combination via the approach of knowledge graph for the treatment of plasma cell mastitis (PCM), a breast inflammation with severe and intense clinical symptoms. The authors evaluated the efficacy of the herbal drug combination in clinical trial, which recruited 160 patients thus far (Trial number: NCT05530226). The clinical trial results showed that the herbal drug combination could significantly reduce the recurrence rate and reverse the clinical symptoms of PCM patients.
The manuscript provides strong evidence for the following,
1. The authors showed that, for the first time, knowledge graph is a useful approach for the identification of herbal drug combination towards plasma cell mastitis. This is novel because in the past, the design of …Reviewer #3 (Public Review):
The manuscript presented the identification of an herbal drug combination via the approach of knowledge graph for the treatment of plasma cell mastitis (PCM), a breast inflammation with severe and intense clinical symptoms. The authors evaluated the efficacy of the herbal drug combination in clinical trial, which recruited 160 patients thus far (Trial number: NCT05530226). The clinical trial results showed that the herbal drug combination could significantly reduce the recurrence rate and reverse the clinical symptoms of PCM patients.
The manuscript provides strong evidence for the following,
1. The authors showed that, for the first time, knowledge graph is a useful approach for the identification of herbal drug combination towards plasma cell mastitis. This is novel because in the past, the design of formulae in TCM is solely based on the principle of 'syndrome differentiation'.
2. The herbal drug combination identified by knowledge graph can markedly suppress various inflammatory cytokines in serum and restore clinical symptoms of PCM patients.
3. The herbal drug combination could reduce the recurrence rate of PCM, a major obstacle for PCM treatment.The major merit of the manuscript is that the authors introduced the concept of knowledge graph into the domain of herbal drugs or TCM. Namely, the authors designed a knowledge graph towards systematic immunity or immunotherapy based on massive data mining techniques. The authors successfully identified an herbal drug combination for PCM with the help of a scoring system. Moreover, the authors conducted a clinical trial study and the clinical data showed that the herbal drug combination holds great promise as an effective treatment for PCM. The weakness of the manuscript is that some details for the herbal drug combination and the clinical trial study are missing.
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