Comments on “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells”

We read with interest the article by Xiaoqiang Wang et al. [1] titled “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells” published in JOR Spine on December 11, 2024. The study presents compelling findings on the role of puerarin in mitigating intervertebral disc degeneration (IDD). However, we would like to raise two critical points regarding the data analysis and interpretation that may affect the validity of the conclusions.

First, in Figure 1E, the intersection size of four different datasets is presented. However, the results appear counterintuitive: the intersection size increases as more datasets are included, while it decreases with fewer datasets. This observation contradicts mathematical principles, as the intersection of multiple datasets typically diminishes with the addition of more datasets due to increased variability and reduced common elements. We suggest that the authors revisit the methodology used to calculate these intersections and verify the data processing steps to ensure accuracy. Clarification on how the intersection sizes were derived would greatly enhance the reliability of this analysis.

Second, the authors did not explicitly state the log2FoldChange threshold used in their differential analysis. Based on Figure 2A, the absolute values appear to range between 0.2 and 0.3. Such a low threshold may result in an overly broad range of differentially expressed genes, potentially reducing the biological significance of the findings [2, 3]. We recommend that the authors justify their choice of threshold and consider applying a more stringent cutoff to improve the robustness of their results. Additionally, exploring the biological relevance of the identified genes through functional enrichment analysis could strengthen the study's conclusions [4].

We believe that addressing these issues would significantly enhance the clarity and impact of the study. We appreciate the authors' contributions to the field and hope that our comments will encourage further refinement of this important work. Thank you for considering our comments. We look forward to the authors' response and any potential follow-up studies.