The Efficacy of Chaihu-Guizhi-Ganjiang Decoction on Chronic Non-Atrophic Gastritis with Gallbladder Heat and Spleen Cold Syndrome and Its Metabolomic Analysis: An Observational Controlled Before-After Clinical Trial [Letter]

Dear editor

We found that the study by Wen et al1 had high clinical research value. The authors utilized numerous biological samples and a visualization scale featuring Chinese medicine characteristics to demonstrate the benefits of Chinese medicine for chronic non-atrophic gastritis (CNAG), specifically through evidence of gallbladder-heat and spleen-cold syndromes. However, we recommend that the authors focus more on the clinical trial design details.

There are concerns regarding the validity of the conclusions drawn from the study design. First, clinical observations and cohort studies2 indicate that smoking, alcohol consumption, dietary habits, and disease duration are more critical and significantly associated with disease outcome and progression but were not included in this study. Furthermore, certain GNAG cases are self-resolving, and patients exhibiting milder symptoms than those with more severe manifestations may experience spontaneous resolution of gastric discomfort after briefly modifying detrimental habits, avoiding stressful environments, or alleviating stress. We considered that patients in this study might not have excluded the aforementioned factors during treatment, or that their influence might have been underestimated, potentially affecting the outcome. Additionally, we suggest that short-term (28 days) regulation of environmental and lifestyle factors may enhance treatment efficacy, potentially synergizing with the drug and offering psychological comfort. Therefore, combining placebo with long-term observation is crucial to effectively demonstrate that CNAG improvement is due to traditional Chinese medicine treatment.

Second, we believe that the plasma BCAA index is significantly related to exercise and lifestyle.3 Plasma samples were collected during fasting to minimize external influences on the BCAA levels. However, it is unclear whether the participants exercised before meals, which could have biased the results. Thus, the link between altered plasma BCAA levels and the gastric environment and motility requires further controlled studies. Additionally, the correlation between GNAG and inflammatory factors is crucial because differential levels before and after treatment indicate a reduction in inflammation. We believe that it would be better to include COX-2, TNF-α, and IL-10 levels4 in the study.

Furthermore, during the administration of Chinese medicines, significant attention has been paid to potential adverse reactions or side effects in patients, such as nausea, vomiting, and diarrhea. The Chaihu-Guizhi-Ganjiang Decoction (CGGD) formula includes herbs such as Scutellaria baicalensis, Juniperus communis root, and dried ginger, which may cause pyrexia, diaphoresis, or mild diarrhea. It is imperative to evaluate the safety profile of CGGD and its potential adverse effects.

This observational study confirmed the efficacy of CGGD by comparing patients pre- and post-treatment with healthy controls. However, the low patient shedding rate and small sample size limited the generalizability of the results. We expect the authors to validate CGGD’s long-term efficacy and mechanism of CGGD with a larger sample size and a more rigorous experimental design. Additionally, we suggest incorporating multi-omics data (eg, transcriptomics and proteomics) for more comprehensive biological insights.

Disclosure

The authors report no conflicts of interest in this communication.