Research Article

Efficacy of Modified Peanut Skin Decoction for Lung Cancer Myelosuppression

DOI:

10.3791/68880

⸱

September 16th, 2025

 ,  ,  ,  ,  , 
1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Hebei North University, 2Department of Cardiothoracic Surgery, The First Affiliated Hospital of Hebei North University, 3Department of Stomatology, The First Affiliated Hospital of Hebei North University, 4College of Traditional Chinese Medicine, Hebei North University, 5Department of Geriatrics, The First Affiliated Hospital of Hebei North University

Corresponding Authors: Zhan-Lin Li <lizhanlin_2023@126.com>

In This Article

Summary

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This study evaluates the efficacy of modified Peanut Skin Decoction (PSD) in alleviating myelosuppression in patients with advanced lung squamous carcinoma receiving chemoimmunotherapy. Clinical outcomes and network pharmacology reveal PSD's mechanisms via phosphoinositide 3-kinase-protein kinase B/hypoxia-inducible factor-1 pathways.

Abstract

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This study conducted a randomized controlled trial to assess the efficacy and safety of modified Peanut Skin Decoction (PSD) for preventing myelosuppression in 60 patients with advanced squamous cell lung carcinoma receiving chemotherapy plus immunotherapy. Patients were randomised 1:1 to receive either standard supportive care granulocyte colony-stimulating factor (5 µg/kg) or supplemented by modified PSD as needed. Primary endpoints included white blood cell count, neutrophil count, haemoglobin level, platelet count, and World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire scores measured on days 4, 8, 12, and 20. Secondary endpoints were onset time, duration, and recovery of grade III-IV myelosuppression, cumulative blood transfusion volumes, and adverse event rates. The results showed that PSD significantly delayed the onset of grade III-IV myelosuppression (5.63 ± 1.10 vs. 4.10 ± 1.24 days; p < 0.001) and shortened its duration (7.07 ± 1.72 vs. 9.97 ± 1.16 days; p < 0.001), while improving WHOQOL-BREF scores without increasing adverse event rates. Network pharmacology revealed that key active components target interleukin-6, tumour necrosis factor, and vascular endothelial growth factor A via the phosphoinositide 3-kinase-protein kinase B and hypoxia-inducible factor-1 signalling pathways, underpinning PSD's protective effects against myelosuppression. Overall, PSD effectively mitigates chemotherapy-induced myelosuppression and enhances patient quality of life.

Introduction

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Lung cancer ranks as the malignancy with the highest incidence and mortality rates in China. Projections suggest that by 2025, the number of patients with lung cancer in China is projected to exceed one million, positioning the nation as the global epicentre of lung cancer burden. Non-small cell lung cancer (NSCLC) constitutes 80%-85% of all lung cancer cases1, with squamous cell carcinoma of the lung accounting for 20%-30% of these instances2. In recent years, the advent of immune checkpoint inhibitors (ICIs) has significantly altered the treatment landscape for advanced squamous cell lung carcinoma, significantly altering clinical practice. The KEYNOTE-024 study was the first to reveal the potent efficacy of ICIs in advanced NSCLC with high programmed death-ligand 1 (PD-L1) expression (PD-L1 ≥50%), although only 18.4% of participants had squamous histology3. The EXPRESS II study established that among patients with advanced NSCLC in the real-world setting in China, just 21.5% of patients with advanced NSCLC exhibited PD-L1 ≥50%4.

Chemotherapy can synergise with ICIs by releasing tumour-associated antigens, remodelling the immune microenvironment, and modulating T-cell function. As a result, ICI-chemotherapy combinations are now the first-line standard for advanced squamous cell lung carcinoma. Although overall haematologic toxicity is lower with ICIs alone than with chemotherapy, myelosuppression remains a common chemotherapy-related adverse effect, disrupting bone marrow cell proliferation and maturation. In severe cases, this can lead to complications, such as infections, anaemia, and bleeding, necessitating dose reductions or impacting the treatment schedule, adversely affecting patient prognosis and even endangering lives5. Granulocyte colony-stimulating factor (G-CSF), commonly used to treat neutropenia, acts quickly but has a short duration of effect, and some patients may experience adverse reactions, such as fever, bone pain, and fatigue6. Severe anaemia or secondary thrombocytopenia necessitates the transfusion of costly and scarce blood products.

Traditional Chinese medicine (TCM) lacks a specific classification for myelosuppression; however, based on clinical manifestations, such as dizziness, fatigue, weakness in the lumbar and knees, palpitations, shortness of breath, bleeding, susceptibility to infections and fever, it can be classified under TCM syndromes such as 'blood deficiency', 'blood syndrome' or 'internal injury fever'7. Chemotherapy drugs, due to their noxious properties, tend to generate 'toxic heat', damaging organ functions and ultimately leading to bone marrow damage. The main pathological mechanisms are identified as spleen and kidney deficiency and insufficient Qi and blood8,9. Clinically, TCM treatment focuses on strengthening the spleen and kidneys and nourishing Qi and blood. As TCM's efficacy in alleviating chemotherapy-induced myelosuppression gains recognition, its role is increasingly valued. Peanut Skin Decoction (PSD), a formula derived from the hospital team's clinical experience in treating myelosuppression, contains peanut skin, Astragalus membranaceus, Herba Agrimoniae, Spatholobus suberectus, Codonopsis pilosula, Colla Corii Asini, Atractylodes macrocephala, Poria, Glycyrrhiza uralensis, Angelica sinensis, Forsythia suspensa, Psoralea corylifolia, Ligustrum lucidum, Eclipta prostrata, and Chinese dates. The peanut skin polyphenolic extract KK4-PSE, when combined with chemotherapy, can not only achieve greater tumour inhibition but also significantly mitigate hepatotoxicity induced by both cisplatin and 5-FU10, aligning with TCM theory and modern pharmacological research findings11. Ingredients such as Colla Corii Asini, peanut skin, Astragalus membranaceus, and Poria fortify the spleen, boost Qi, nourish blood, and consolidate the body's foundation, regulating immunity12. Ligustrum lucidum, Eclipta prostrata, and Chinese dates strengthen the kidney, replenish deficiency, and promote haematopoiesis. Current interventions rely on short-acting G-CSF injections and blood transfusions, which frequently cause medullary bone pain (reported in 20%-38% of patients) and may necessitate treatment delays or hospital admissions13,14. Bronze flavonoid-rich peanut skin polyphenols exhibit potent antioxidant and anti-inflammatory properties, suggesting that modified PSD may offer sustained haematopoietic support with fewer side effects and reduced healthcare burden11.

Therefore, this protocol focuses on stage IV squamous non-small cell lung carcinoma patients aged 18-75 years with Qi-blood deficiency undergoing four cycles of standard chemotherapy plus immunotherapy. Modified PSD (30 g peanut skin decocted in 500 mL water at 100 °C for 30 min, filtered through a 200-mesh sieve, administered warm in two divided doses 30 min post-meal) is assessed for its efficacy in mitigating chemotherapy-induced myelosuppression. Network pharmacology and molecular docking analyses are used to elucidate the formula's key active components and core molecular targets, providing mechanistic insight and clinical application guidance.

Protocol

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This protocol was approved by the Ethics Committee of the First Affiliated Hospital of Hebei North University (No. W2021018) and adheres to the Declaration of Helsinki. All participants were informed and provided signed consent forms. The reagents, equipment, software, and database URLs used are listed in the Table of Materials.

1. Clinical study

  1. Study participants
    Using a convenience sampling approach, data were collected from 60 patients treated at the Traditional Chinese Medicine Oncology Department of the First Affiliated Hospital of Hebei North University between January 2021 and October 2022. These patients had completed four cycles of first-line treatment for advanced squamous cell carcinoma of the lung, consisting of sintilimab (200 mg on day 1), gemcitabine (1,000 mg/m2 on days 1 and 8), and cisplatin (75 mg/m2 on days 1 and 2). The patients were randomly divided into an observation group and a control group, with 30 patients in each group.
    The inclusion criteria were as follows: (1) Western medicine diagnosis based on the New Guidelines for the Diagnosis and Treatment of Common Malignant Tumors15, meeting the diagnostic criteria for primary lung cancer, with histological or cytological confirmation of squamous cell carcinoma of the lung, assessed as stage IV by imaging; (2) a TCM diagnosis in line with the Clinical Guiding Principles for New Traditional Chinese Medicine Drugs16, consistent with Qi and blood deficiency differentiation; (3) aged 18-75 years; (4) an estimated survival period >3 months; (5) voluntary participation in the study with signed informed consent; (6) Grade III-IV myelosuppression, defined according to the Common Terminology Criteria for Adverse Events v5.0 criteria as white blood cell (WBC) count < 2.0 × 109/L or ANC count < 1.0 × 109/L for grade III and WBC count <1.0 × 109/L or ANC <0.5 × 109/L for grade IV; and (7) last chemotherapy session completed within 3 days prior to enrolment.
    The exclusion criteria were as follows: (1) patients with mental disorders unable to cooperate with researchers or those with primary tumours at other sites; (2) allergies to any Chinese medicine ingredients used in this study; (3) uncontrollable infections or bleeding; or (4) severe cardiovascular or other organ dysfunctions.
  2. Preparation of decoction
    The ingredients of the modified PSD comprised peanut skin (30 g), Astragalus membranaceus (30 g), Herba Agrimoniae (30 g), Spatholobus suberectus (30 g), Codonopsis pilosula (24 g), Colla Corii Asini (10 g), Atractylodes macrocephala (15 g), Poria (15 g), Glycyrrhiza uralensis (10 g), Angelica sinensis (6 g), Forsythia suspensa (15 g), Psoralea corylifolia (10 g), Ligustrum lucidum (15 g), Eclipta prostrata (15 g) and Chinese dates (10 pieces).
    The preparation process began by soaking herbs in a ceramic decoction pot with 500 mL purified water for 30 min. This was heated to a rolling boil (100 °C) and maintained for 30 min, stirring every 10 min. The mixture was filtered through a 200-mesh sieve into a sterile container, and the residue was discarded.
  3. Study groups and treatment procedure
    Control group: received symptomatic supportive care. If fever was present, sensitive antibiotics were administered. If haemoglobin (Hb) was <60 g/L, suspended red blood cells were transfused. If the platelet (PLT) count was <30 × 109/L and there was a risk of spontaneous bleeding, PLT transfusions were given, continuing for 2 weeks.
    Observation group: all control-group treatments plus modified PSD (see step 1.2.1, Preparation of decoction'). The decoction was administered warm (≈40 °C) in two divided doses (250 mL each), 30 min after breakfast and dinner, with the patient seated upright. Patients were instructed to record each dose in an adherence log.
  4. Data collection
    For data collection, the following steps were followed: (1) General data: gender, age, and duration of illness; (2) Collection of post-treatment WBC count, NEU count, Hb level, and PLT count on days 4, 8, 12, and 20; (3) Documentation of the occurrence, duration, and recovery times of grade III-IV bone marrow suppression (defined by any of the following criteria: WBC count <2 × 109/L, NEU count < 1.0 × 109/L, Hb level <80 g/L, PLT count <50 × 109/L); (4) Collection of quality of life scores before treatment and at weeks 1 and 2 post-treatment. The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) questionnaire was utilised to assess the quality of life scores of two groups of patients with advanced lung squamous carcinoma before and after the fourth cycle of chemotherapy combined with immunotherapy. This questionnaire comprises 26 items, 2 general items and 24 items across four domains (physical health, psychological health, social relationships, and environment), each scored on a 5-point Likert scale (total score range: 26-130). Higher scores indicate better quality of life17; (5) Collection of liver function indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) and renal function indicators (serum creatinine [CREA], Na+, K+ levels) before treatment and on day 8 post-treatment; (6) Adverse reactions during treatment, including liver function impairment (elevated ALT and/or AST), renal function impairment (elevated CREA), electrolyte disturbances (abnormal serum sodium, potassium, chloride levels) and electrocardiogram abnormalities (arrhythmias or new-onset myocardial ischaemia).
  5. Safety and waste disposal
    Adverse reactions were monitored at each visit, and decoction residues were disposed of as per hospital biohazard procedures.
  6. Statistical analysis
    All data were statistically analysed using the SPSS software. Normality testing was conducted using the Kolmogorov-Smirnov test. For measurement data conforming to a normal distribution, mean ± standard deviation was used for presentation, and independent sample t-tests were applied. Repeated measurement data were analysed using repeated measures analysis of variance (ANOVA). Enumeration data were expressed as frequency (n) or percentage (%) and analysed using the χ2 test. A two-tailed p-value of <0.05 was considered a statistically significant difference.

2. Network pharmacology

  1. Acquisition, screening, and target prediction of main active components
    The chemical components of modified PSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Encyclopedia of Traditional Chinese Medicine (ETCM)18,19 database. Active components were screened based on their pharmacokinetic parameters. The two-dimensional structures and canonical SMILES of the active components were obtained from PubChem20, and potential targets were predicted using SwissTargetPrediction21. All predicted targets were validated against UniProt22.
  2. Disease target and drug-disease target prediction
    Disease targets related to 'myelosuppression' or 'bone marrow suppression' were identified via the GeneCards23 and Online Mendelian Inheritance in Man (OMIM)24databases, then validated using UniProt22. After deduplication, the disease targets related to myelosuppression/bone marrow suppression were obtained, and the intersection of these disease targets with the drug active component targets was identified as the potential therapeutic targets of modified PSD for treating bone marrow suppression.
  3. Construction of a drug component-target network
    The intersection targets of bone marrow suppression-related genes and the active components of modified PSD were analysed using the Venny 2.1 platform to identify potential therapeutic targets. The 'drug component-disease target' relationship network was visualised using Cytoscape 3.8.2 software.
  4. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis
    Potential therapeutic targets were subjected to gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Targets were imported into the DAVID database, with the species and background set to 'Homo sapiens'. The top 10 cellular components (CCs), biological processes (BPs), and molecular functions (MFs), and the top 20 key signalling pathways, ranked by p-value, were selected.
  5. Protein-protein interaction network construction
    To further elucidate the synergistic mechanisms of modified PSD targets and disease targets at the protein level, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database25 was used to predict the protein interaction relationships of core targets. Intersection target data were imported into the STRING database, setting the research species to 'Homo sapiens', the minimum required interaction score to 'highest confidence' (0.900), and discrete nodes were hidden to construct the protein-protein interaction (PPI) network diagram, identifying the core targets of modified PSD in treating bone marrow suppression.
  6. Molecular docking
    Molecular docking was performed between top-ranked drug components in the drug component-target network and top-ranked target proteins in the PPI network. Molecular structures of drug components were obtained in mol2 format from the TCMSP database, and three-dimensional molecular structures of target proteins in Protein Data Bank (PDB) format were obtained from the PDB database. The component and target gene structure files were processed using AutoDockTools and AutoDock Vina software for molecular docking.

Results

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Clinical study section
General information
The results indicated that the observation group consisted of 30 patients, comprising 16 men and 14 women, averaging 59.10 ± 6.56 years of age; the control group also consisted of 30 patients, with 17 men and 13 women, averaging 58.97 ± 6.22 years of age. No statistically significant differences were observed between the two groups in terms of gender, age or duration of illness (p > 0.05), as shown in Table 1.

Comparison of white blood cell, neutrophil, haemoglobin, and platelet levels post-treatment
Univariate repeated measures ANOVA was employed to explore the impact of different treatment methods on WBC, NEU, Hb, and PLT levels within 20 days. The Shapiro-Wilk test indicated that the data in each group followed an approximately normal distribution (p > 0.05). Mauchly's test of sphericity confirmed that the variance-covariance matrices of each group were equal (p > 0.05). Data were presented as x̄ ± s, as shown in Table 2. The results are summarised below.

The interaction effects of time × treatment on Hb and PLT levels were significant (FHb interaction = 13.572, FPLT interaction = 11.985, both p < 0.0001), indicating that the effects of different treatment methods on Hb and PLT levels at four time points varied. Additionally, WBC, NEU, Hb, and PLT levels in both groups changed over time (FWBC time = 46.612, FNEU time =3.398, FHb time =8.764, FPLT time = 30.168, all p < 0.0001). Finally, different treatment methods had varying impacts on WBC, NEU, Hb, and PLT levels (FWBC treatment = 12.416, FHb treatment = 92.43, FPLT treatment =57.672, all p < 0.0001). Further comparison of WBC, NEU, Hb, and PLT levels at 4, 8, 12, and 20 days post-treatment revealed that the observation group had higher WBC and Hb levels at 12 and 20 days, higher NEU levels at 12 days, and higher PLT levels at 8 and 12 days than the control group (p < 0.05).

Comparison of post-treatment data
The findings revealed that the onset of grade III-IV myelosuppression in the observation group occurred later than in the control group (5.63 ± 1.10 vs. 4.10 ± 1.24 days), with a shorter duration (7.07 ± 1.72 vs. 9.97 ± 1.16 days) and a faster recovery time (12.17 ± 0.20 vs. 15.17±1.12 days), all with p < 0.05 (Table 3).

Comparison of quality-of-life brief version scores between groups
Similarly, using one-way repeated measures ANOVA, the impact of different treatment modalities on patients' WHOQOL-BREF scores within 2 weeks was explored. The Shapiro-Wilk test confirmed that the data for each group approximated a normal distribution (p > 0.05); Mauchly's test of sphericity indicated homogeneity of variance-covariance matrices across groups (p > 0.05). Data were expressed as x ± s, as shown in Supplementary Table 1. The results are summarised below.

The interaction between time and treatment on WHOQOL-BREF scores was significant (FQOL-BREF interaction = 137.262, p < 0.0001), indicating that the magnitude of the effect of different treatments on WHOQOL-BREF scores varied across three time points. Moreover, WHOQOL-BREF scores in both groups changed over time (FQOL-BREF time = 32.848, p < 0.0001). Finally, the impact of different treatment modalities on WHOQOL-BREF scores varied (FQOL-BREF treatment =91.908, p < 0.0001). Further comparison of WHOQOL-BREF scores at weeks 1 and 2 showed that the observation group had higher scores than the control group at both time points (p < 0.05).

Comparison of liver and kidney function indicators post-treatment
Post-treatment comparison of ALT, AST, CREA, Na+, and K+ levels between the two groups showed no statistically significant differences (all p > 0.05), indicating no differential impact of treatment modalities on liver and kidney function indicators between the groups, as shown in Supplementary Table 2.

Comparison of adverse reactions post-treatment
The observation group experienced four cases of liver function impairment, two cases of kidney function impairment, and five cases of electrolyte imbalance, with an adverse reaction rate of 36.7%. The control group experienced six cases of liver function impairment, one case of kidney function impairment, seven cases of electrolyte imbalance, and one case of electrocardiograph abnormalities, with an adverse reaction rate of 50.0%. The difference in adverse reaction rates between the two groups was not statistically significant (χ2 = 1.086, p = 0.297), as shown in Supplementary Table 3.

Network pharmacology section

Acquisition and screening of compound components
A total of 400 compound components of PSD were retrieved from the TCMSP and ETCM databases. Following a screening process using criteria of oral bioavailability ≥30% and drug likeness ≥0.18, key effective components were identified. The Swiss Target Prediction platform was then utilized to predict the targets of the potential chemical components of each herb, selecting 'Homo sapiens' as the species. Using the median probability value of 0.105 as a threshold, the targets for the potential active ingredients were screened. The final quantities of potential active ingredients obtained for each herb were as follows: 10 for peanut skin, 15 for Astragalus mongholicus, 5 for Hairyvein Agrimony, 12 for Spatholobus suberectus, 6 for Codonopsis pilosula, 8 for Donkey-hide gelatin, 6 for Atractylodes macrocephala, 4 for Poria, 6 for prepared liquorice root, 6 for Angelica sinensis, 11 for Forsythia suspensa, 47 for Malaytea Scurfpea Fruit, 11 for Ligustrum, 10 for Eclipta, and 9 for Jujube.

Prediction of compound targets and disease-related targets
After consolidation and deduplication of the potential active ingredients, a total of 113 compound-related targets were obtained from the TCMSP and Swiss databases. In the GeneCards and OMIM databases, 7,649 disease-related targets were retrieved, and 2,946 disease targets were filtered using a 'score ≥4.0' criterion. Based on the obtained targets, to study the interactions, BPs, and pathways of the targets, an intersection of 113 compound targets and 2,946 myelosuppression-related targets was identified, 62 intersecting targets, as illustrated in Figure 1A.

Construction of active ingredient-target network
Utilising the aforementioned analysis, active ingredients and potential targets were imported into Cytoscape 3.8.2 software to construct an active ingredient-target network, as shown in Figure 1B. The network comprised 131 nodes and 248 edges. Arrows denote the active ingredients of PSD, ellipses represent potential targets, and the lines between nodes represent their corresponding relationships. Each active ingredient can act on multiple potential targets, reflecting the multi-component, multi-target effects of PSD.

Gene ontology analysis
Gene ontology analysis primarily includes BPs, CCs, and MFs, with BPs being the most critical. To investigate the BPs of PSD in treating myelosuppression, 62 potential targets were imported into the DAVID database for GO analysis. A total of 503 GO terms were obtained, including 267 BP terms, 45 CC terms, and 84 MF terms. Using −Log10p as the screening standard, the top 10 BP, CC, and MF GO terms were selected and analysed, as depicted in Figure 2A. The length of the bar represents the number of genes enriched in the GO term, and the colour represents the −Log10p value. The top five predicted BP terms were 'positive regulation of ERK1 and ERK2 cascade', 'positive regulation of transcription from RNA polymerase II promoter', 'positive regulation of nitric oxide biosynthetic process', 'negative regulation of apoptotic process' and 'positive regulation of cell proliferation'. The top five CCs were 'plasma membrane', 'perinuclear region of cytoplasm', 'cytoplasm', 'cell surface' and 'extracellular region'. The top five MFs were 'enzyme binding', 'protein binding', 'RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding', 'nitric-oxide synthase regulator activity' and 'glycoprotein binding'.

Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis
The 62 potential targets were imported into the DAVID database for KEGG pathway enrichment analysis related to the treatment of myelosuppression with PSD. A total of 111 significantly enriched KEGG pathways were obtained. Using the p-value as the criterion, the top 20 signalling pathways were selected and analysed, as illustrated in Figure 2B. The horizontal axis represents the ratio of enriched genes to all genes in the pathway, the colour of the circles represents the −Log10p value, and the size of the circles represents the number of enriched genes. Pathways related to myelosuppression were mainly enriched in the phosphoinositide 3-kinase-protein kinase B (PI3K-Akt) signalling pathway, hypoxia-inducible factor (HIF)-1 signalling pathway, vascular endothelial growth factor (VEGF) signalling pathway, and oestrogen pathway.

Protein-protein interaction network construction
To predict inter-target relationships and identify core targets, 62 potential targets were imported into the STRING database to construct a PPI network, which was then visualised as shown in Figure 3A. This PPI network comprises 58 nodes (with 4 target proteins not participating) and 374 interaction lines. Nodes correspond to the proteins associated with potential targets, with the size of a node indicating the degree value of that target protein - the larger the node is, the greater its degree value within the network. Lines between nodes signify potential interaction relationships between target proteins. The network underwent cluster analysis using the MCODE plugin in Cytoscape 3.8.2, resulting in the identification of a core subnetwork with the highest score, as depicted in Figure 3B. This subnetwork, scoring 15.29, involves 18 proteins deemed to have significant roles within the PPI. Further analysis using the Cytohubba plugin led to the selection of hub proteins, with the interaction diagram presented in Figure 3C. Darker-coloured proteins indicate stronger interactions, whereas lighter-coloured ones suggest weaker interactions. The intersection of proteins with higher scores from six algorithms identified tumour necrosis factor (TNF), interleukin (IL)-6, VEGF-A, steroid receptor coactivator (SRC), Harvey rat sarcoma viral oncogene homolog (HRAS), and signal transducer and activator of transcription 3 (STAT3) as the hub proteins.

Molecular docking
The IGEMDock v2.1 software package was utilised for molecular docking between the six hub proteins (IL-6, TNF, SRC, VEGF-A, STAT3, HRAS) selected through network pharmacology and 28 active components involved in the network pharmacology construction. Four compounds, Campneoside II, Darendoside B, Leucosceptoside A, and Purpureaside C, demonstrated stable binding with all six hub proteins, as indicated in Supplementary Table 4. This suggests their potential as pharmacologically active components in modified PSD for treating myelosuppression.

DATA AVAILABILITY:
The raw data is provided in Supplementary File 1.

Venn diagram of constituent vs. disease targets, target interaction network analysis graph.
Figure 1: Network pharmacology analysis of modified peanut skin decoction. (A) Venn diagram of component-related targets and disease-related targets. (B) Network diagram of active ingredients and myelosuppression targets (HSYD: Modified peanut skin decoction). Please click here to view a larger version of this figure.

Cancer pathway analysis graph with gene ratio, count, and p-value in dot plot and bar charts.
Figure 2: Functional enrichment analysis of modified peanut skin decoction. (A) Gene oncology analysis diagram of modified peanut coat decoction for treating myelosuppression. (B) Kyoto encyclopedia of genes and genomes pathway enrichment analysis diagram of modified peanut skin decoction for treating myelosuppression. Please click here to view a larger version of this figure.

Network analysis diagram of gene interactions; includes connectivity, node metrics; research data.
Figure 3: Protein-protein interaction network of key targets. (A) Protein-protein interaction diagram of potential action targets. (B) Core subnetwork with the strongest interactions among potential action targets. (C) Protein-protein interaction diagram of hub proteins selected by six algorithms. Please click here to view a larger version of this figure.

Table 1: Comparison of general data. Please click here to download this Table.

Table 2: Comparison of whiteblood cell, neutrophil, haemoglobin, and platelet levels between the two groups post-treatment. Please click here to download this Table.

Table 3: Comparison of post-treatment data. Please click here to download this Table.

Supplementary Table 1: Comparison of World Health Organization Quality of Life Brief Version scores between groups. Please click here to download this File.

Supplementary Table 2: Comparison of liver and kidney function-related indexes post-treatment. Please click here to download this File.

Supplementary Table 3: Comparison of adverse reactions post-treatment between groups (cases [%]). Please click here to download this File.

Supplementary Table 4: Molecular docking results. Please click here to download this File.

Discussion

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In this randomised study of 60 patients with advanced-stage squamous lung carcinoma (stage IV), modified PSD demonstrated significant protective effects against severe haematological toxicity. Specifically, PSD administration prolonged the latency to grade III-IV myelosuppression onset and shortened its duration compared with standard supportive care. Concomitantly, patients receiving PSD exhibited clinically meaningful improvements in quality-of-life metrics (WHOQOL-BREF scores increased at Week 2), and elevated WBC, NEU, Hb, and PLT levels, without increasing adverse event incidence. Integrated network pharmacology and molecular docking revealed that bioactive constituents - particularly Campneoside II and Leucosceptoside A - engage pivotal targets (IL-6, TNF, VEGF-A) via modulation of PI3K-Akt and HIF-1 signalling cascades, providing a molecular rationale for the observed clinical benefits.

The clinical manifestations of myelosuppression, triggered by the combined application of ICIs combined with chemotherapy, resonate with the TCM paradigm of 'deficiency fatigue', predominantly characterised by Qi-blood deficiency and spleen-kidney impairment. The modified PSD formula integrates peanut inner skin, drawing inspiration from Danggui Buxue Decoction combined with Sijunzi Decoction and Erzhi Pill. As delineated in the 'Compendium of Materia Medica', Astragalus mongholicus is considered the 'chief of Qi tonics, capable of treating all Qi deficiency and blood decline syndromes'. The tangible blood is generated from intangible Qi, and Astragalus mongholicus replenishes the Qi of the lungs and spleen to nourish the source of transformation26. Beyond fortifying the spleen, replenishing Qi, and enriching blood, PSD also tonifies the kidneys and fosters marrow production. Erzhi Pill, comprising wine-processed Ligustri Lucidi Fructus from Ligustrum lucidum and Ecliptae Herba from Eclipta prostrata in a 1:1 ratio27, nourishes the liver and kidneys and enriches yin and blood, and Psoralea corylifolia warms the kidneys and assists yang, facilitating the recovery of haematopoietic function. Agrimonia Pilosa (praised by Gan Zuwang as the 'hormone of Chinese medicine') and Forsythia suspensa are paired clinically to tonify deficiency, cool blood and arrest bleeding, while Spatholobus suberectus promotes circulation and has been shown to elevate leukocyte counts and correct anaemia28. Previous meta-analyses have demonstrated that Astragalus (HuangQi) injection reduced the incidence of chemotherapy-induced leukopenia by approximately 25%29, aligning with our utilisation of Astragalus mongholicus as a key Qi-tonifying component. Similarly, although complex TCM injections, such as Aidi, have shown promise in improving clinical efficacy and reducing overall chemotherapy toxicity in advanced NSCLC when combined with platinum-based regimens30, PSD's specific breakthrough lies in mitigating severe myelosuppression timing and duration.

Analysis of the 62 potential targets in modified PSD revealed that IL-6, TNF-α, SRC, VEGF-A, HRAS and STAT3 are the core targets for treating myelosuppression. Crucially, molecular docking confirmed Campneoside II, Darendoside B, Leucosceptoside A, and Purpureaside C as key bioactive components that exhibited stable binding to all six hub proteins, providing a structural basis for PSD's multi-target effects. Interleukin-6 from bone marrow stroma drives haematopoietic stem cell (HSC) proliferation and differentiation, expanding erythroid/granulocyte lineages to increase peripheral NEUs, erythrocytes, and PLTs31. It synergises with IL-3 to activate early progenitor cell cycling32. Vascular endothelial growth factor A maintains HSC survival and function within the bone marrow niche33,34. Its knockout impairs stem cell viability and colony formation, whereas agonism enhances proliferation, establishing its critical regulatory role35. Tumour necrosis factor-α activates nuclear factor kappa B/ extracellular signal-regulated kinases (ERKs) to induce NO synthase and cytotoxic NO, triggering HSC apoptosis, and downregulates GATA-1/FOG-1 (while upregulating GATA-2) to inhibit erythropoietin (EPO) signalling and erythropoiesis36,37,38. Steroid receptor coactivator 3 sustains long-term HSC function by modulating GCN5-PGC-1α-mediated mitochondrial metabolism39; it transduces cytokine signals through janus kinase (JAK)-STAT, with JAK2-STAT3 activation providing radioprotection to haematopoietic cells40. Studies isolating proanthocyanidin A1 from peanut skin demonstrated its direct binding to JAK2, activating the JAK2-STAT3 pathway to promote megakaryocyte proliferation/differentiation and effectively treat chemotherapy-induced thrombocytopenia41. This finding provides direct experimental validation for our network pharmacology prediction and highlights PSD's four key components (e.g. Campneoside II or Purpureaside C) as likely contributors to this STAT3-mediated pro-haematopoietic activity. Furthermore, PSD's multi-target approach fundamentally differs from single-target biological agents, such as the anti-IL-6 monoclonal antibody tocilizumab42. Although tocilizumab effectively blocks one specific cytokine signal (IL-6), it cannot address the concurrent dysregulation of other critical targets identified here (TNF-α, SRC, VEGF-A, HRAS). Molecular docking confirms that PSD achieves its integrated effect through the high-affinity binding of multiple key bioactive components (e.g., Campneoside II to IL-6/TNF-α/STAT3, Purpureaside C to VEGF-A/HIF-1α) to these diverse core targets simultaneously, exemplifying a superior multi-target synergistic strategy.

Further elaboration of the network pharmacology findings reveals that these 62 intersecting targets are highly enriched in BPs that directly support haematopoietic recovery. The gene ontology analysis results highlighted the negative regulation of apoptotic processes and the positive regulation of cell proliferation as predominant mechanisms, with additional enrichment in ERK1/2 cascade modulation, all aligning with the observed peripheral blood count improvements. Notably, the PPI network decomposition demonstrated functional clustering: TNF/IL-6/STAT3 governing apoptosis inhibition (GO:0043066) and VEGF-A/SRC/HRAS orchestrating cell proliferation (GO:0008284), with STAT3-HRAS serving as critical communication nodes between clusters.

Transitioning to pathway-level insights, KEGG enrichment analysis indicates that the pathways implicated in the intervention of myelosuppression by the augmented decoction predominantly include the PI3K-Akt pathway (38% targets, p <0.001), HIF-1 pathway (32%, p = <0.001), oestrogen pathway (24%, p = <0.001) and VEGF pathway (29%, p = <0.001). Specifically, the PI3K-Akt signalling (enriched by 21 PSD compounds) serves as the central coordinator, playing a pivotal role in the maintenance of homeostasis and directed differentiation of HSCs. Aberrant activation of this pathway leads to a reduction in HSC self-renewal, disrupting the maintenance of HSC homeostasis and resulting in HSC exhaustion; conversely, aberrant inactivation of this pathway results in severe impairment of haematopoietic differentiation capabilities43. The PI3K-Akt pathway is also a crucial regulator of EPO/EPOR, governing processes such as the proliferation, apoptosis, and autophagy of erythrocytes, which are vital for erythropoiesis. Hypoxia-inducible factors are key mediators in the HSC hypoxic response pathway, with HIF-1 and HIF-2 jointly regulating HSC survival, quiescence, and differentiation; HIF-1α controls HSC metabolism, glycolysis, respiration, and oxidative stress, thereby governing self-renewal and differentiation44, and HIF-2α primarily supports erythropoiesis through EPO induction and iron metabolism maintenance, acting via stromal mediators45. As HIF's downstream effector46, VEGF reinforces the vascular niche for HSCs, and oestrogen signalling (directly or via the niche) promotes HSC S-phase entry and skews self-renewal toward megakaryocyte-erythroid progenitors47,48,49. Collectively, these multi-component, multi-target interactions demonstrate that PSD restores haematopoietic homeostasis through three synergistic mechanisms: (1) Campneoside II-mediated PI3K-Akt activation enhances EPO receptor expression and erythroid survival; (2) HIF-1/VEGF axis modulation (particularly by Purpureaside C) reinforces vascular niche support under hypoxic stress; (3) Oestrogen-HRAS signalling coordination promotes HSC self-renewal and megakaryocyte-erythroid commitment - mechanistic insights that integrate our PPI network and molecular docking findings with clinical outcomes.

During decoction preparation, maintaining a stable 100 °C rolling boil for 30 min is essential for consistent extraction of active constituents; if uneven heating or temperature drop is observed, the boil should be extended by an additional 5 min while stirring every 10 min. After decoction, the decoction should be filtered through a 200-mesh sieve to remove insoluble residues; if particles persist, the filtrate should be returned to the pot, stirred gently for 1 min, and re-filtered. To ensure patient adherence, the dosing logs should be reviewed at each visit; if a patient misses two consecutive doses, a telephone reminder system should be implemented. Additionally, any decoction residues should be collected and disposed of following hospital biohazard protocols to maintain safety and hygiene.

This study has several limitations. First, the relatively small sample size and the single-centre design may introduce random errors. Future studies will include a larger number of cases to fully validate the findings. Second, this study primarily focuses on short-term therapeutic effects, with an absence of observations on long-term survival rates and adverse reactions. Long-term follow-ups are recommended to comprehensively assess the therapeutic efficacy of the augmented Peanut Coat Decoction. Lastly, this study was confined to network pharmacology analysis for an initial exploration of potential pharmacological mechanisms, necessitating further corroboration through animal experiments.

Modified PSD is efficacious in mitigating myelosuppression and enhancing the quality of life in patients undergoing chemotherapy combined with immunotherapy for advanced squamous cell lung carcinoma. Adverse event rates were comparable between the PSD and control groups, indicating that PSD does not increase treatment-related toxicity. Network pharmacology results indicate that active components of the decoction, such as Campneoside II, Darendoside B, Leucosceptoside A, and Purpureaside C, target key molecules, including IL-6, VEGF-A, TNF, STAT3, HRAS, and SRC. Through pathways such as the PI3K-Akt signalling pathway, HIF-1 signalling pathway, VEGF signalling pathway, and oestrogen pathway, these components exert therapeutic effects on myelosuppression.

Disclosures

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

The authors have no conflicts of interest to declare.

Acknowledgements

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,

This work was supported by the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine (2022423).

Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Angelica sinensisXiangxue Pharmaceutical Co., Ltd.
XSQ-AS-2021-10		-Dried, 6 g per dose
Astragalus membranaceusXiangxue Pharmaceutical Co., Ltd.
XSQ-AM-2021-02		-Dried, 30 g per dose
Atractylodes macrocephalaXiangxue Pharmaceutical Co., Ltd.
XSQ-AMa-2021-07		-Dried, 15 g per dose
AutoDock ToolsScripps Research Institutehttp://autodock.scripps.eduv1.5.6
AutoDock VinaScripps Research Institutehttp://vina.scripps.eduv1.1.2
Chinese datesXiangxue Pharmaceutical Co., Ltd.
XSQ-CZ-2021-15		-10 pieces per dose
Codonopsis pilosulaXiangxue Pharmaceutical Co., Ltd.
XSQ-CP-2021-05		-Dried, 24 g per dose
Colla Corii AsiniXiangxue Pharmaceutical Co., Ltd.
XSQ-CA-2021-06		-10 g per dose
CytoscapeCytoscape Consortiumhttps://cytoscape.orgv3.6.0
DAVIDNIAIDhttps://david.ncifcrf.gov-
Decoction apparatusCeramic pot-Capacity ≥1 L, used for herbal decoction
Eclipta prostrataXiangxue Pharmaceutical Co., Ltd.
XSQ-EP-2021-14		-Dried, 15 g per dose
ETCMTCMIPhttp://www.tcmip.cn/ETCM-
Forsythia suspensaXiangxue Pharmaceutical Co., Ltd.
XSQ-FS-2021-11		-Dried, 15 g per dose
GeneCardsWeizmann Institutehttps://www.genecards.org-
Glycyrrhiza uralensisXiangxue Pharmaceutical Co., Ltd.
XSQ-GU-2021-09		-Dried, 10 g per dose
Herba AgrimoniaeXiangxue Pharmaceutical Co., Ltd.
XSQ-HA-2021-03		-Dried, 30 g per dose
Ligustrum lucidumXiangxue Pharmaceutical Co., Ltd.
XSQ-LL-2021-13		-Dried, 15 g per dose
OMIMJohns Hopkins Universityhttps://omim.org-
PDBRCSBhttps://www.rcsb.org-
Peanut skinXiangxue Pharmaceutical Co., Ltd.
XSQ-PS-2021-01		-Dried, 30 g per dose
Platelet concentrateGeneric--
PoriaXiangxue Pharmaceutical Co., Ltd.
XSQ-P-2021-08		-Dried, 15 g per dose
Psoralea corylifoliaXiangxue Pharmaceutical Co., Ltd.
XSQ-PC-2021-12		-Dried, 10 g per dose
PubChemNCBIhttps://pubchem.ncbi.nlm.nih.gov-
Recombinant human G-CSFGeneric-5 μg/kg, subcutaneous injection
Sensitive antibioticsGeneric--
Spatholobus suberectusXiangxue Pharmaceutical Co.,
Ltd. XSQ-SS-2021-04		-Dried, 30 g per dose
SPSSIBMv26.0
STRINGELIXIRhttps://string-db.org-
Suspended red blood cellsGeneric--
Swiss Target PredictionSIBhttp://www.swisstargetprediction.ch-
TCMSPNWUhttp://lsp.nwu.edu.cn/tcmsp.php-
UniProtEMBL-EBIhttps://www.uniprot.org-
VennyBioInfoGPhttps://bioinfogp.cnb.csic.es/tools/venny/v2.1
WHOQOL-BREFWHOhttps://www.who.int/tools/whoqol-

References

$$\rightleftharpoonup{xx}$$ $$\longleftharp{xx}$$, $$\longrightharp{xx}$$,
  1. Research progress in the efficacy and safety of alk inhibitors in the treatment of NSCLC brain metastasis. Zhongguo Fei Ai Za Zhi. 26 (5), 400-406 (2023).">Chen, Y., Han, H., Wei, J., Du, Q., Wang, X. Research progress in the efficacy and safety of alk inhibitors in the treatment of NSCLC brain metastasis. Zhongguo Fei Ai Za Zhi. 26 (5), 400-406 (2023).
  2. Linc00626 promotes the proliferation, invasion and metastasis of lung squamous cell carcinoma via the Jak1/stat3 signaling pathway. Guangdong Medical J. 44 (7), 793-802 (2023).">Hui-Fang, C., Lin-Lin, F., Hui-Qin, S., Li, L., Hai-Tao, W. Linc00626 promotes the proliferation, invasion and metastasis of lung squamous cell carcinoma via the Jak1/stat3 signaling pathway. Guangdong Medical J. 44 (7), 793-802 (2023).
  3. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 375 (19), 1823-1833 (2016).">Reck, M., et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 375 (19), 1823-1833 (2016).
  4. Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: The global, multicenter express study. Lung Cancer. 134, 174-179 (2019).">Dietel, M., et al. Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non-small-cell lung cancer: The global, multicenter express study. Lung Cancer. 134, 174-179 (2019).
  5. Correlations between bone marrow radiation dose and hematologic toxicity in locally advanced cervical cancer patients receiving chemoradiation with cisplatin: A systematic review. Radiother Oncol. 164, 128-137 (2021).">Corbeau, A., et al. Correlations between bone marrow radiation dose and hematologic toxicity in locally advanced cervical cancer patients receiving chemoradiation with cisplatin: A systematic review. Radiother Oncol. 164, 128-137 (2021).
  6. Large-vessel vasculitis induced by granulocyte colony-stimulating factor administration after chemotherapy. Mod Rheumatol Case Rep. 5 (2), 322-326 (2021).">Yamamoto, K., et al. Large-vessel vasculitis induced by granulocyte colony-stimulating factor administration after chemotherapy. Mod Rheumatol Case Rep. 5 (2), 322-326 (2021).
  7. Discussion on Chinese medicine theory and treatment ideas of myelosuppression after chemotherapy. Clin J Chinese Med. 11 (05), 23-25 (2019).">Yi'nan, Y., Yali, Z. Discussion on Chinese medicine theory and treatment ideas of myelosuppression after chemotherapy. Clin J Chinese Med. 11 (05), 23-25 (2019).
  8. Research progress on Chinese materia medica in treatment of chemotherapy-induced leukopenia. Chinese Tradit Herb Drugs. 20, 5088-5095 (2019).">Xt, Q., et al. Research progress on Chinese materia medica in treatment of chemotherapy-induced leukopenia. Chinese Tradit Herb Drugs. 20, 5088-5095 (2019).
  9. Discussion on Chinese medicine treatment ideas of myelosuppression after tumor chemotherapy. Journal of Medical Research. 05, 183-184 (2017).">Ln, W., Wj, W. Discussion on Chinese medicine treatment ideas of myelosuppression after tumor chemotherapy. Journal of Medical Research. 05, 183-184 (2017).
  10. Anticancer potential of Valencia peanut (Arachis hypogaea l.) skin extract against cervical cancer cells in vitro and in nude mouse xenograft models. Foods. 13 (15), 2354(2024).">Jeeunngoi, J., et al. Anticancer potential of Valencia peanut (Arachis hypogaea l.) skin extract against cervical cancer cells in vitro and in nude mouse xenograft models. Foods. 13 (15), 2354(2024).
  11. Extracts of peanut skins as a source of bioactive compounds: Methodology and applications. Appl. Sci. 10 (23), 8546(2020).">Dean, L. L. Extracts of peanut skins as a source of bioactive compounds: Methodology and applications. Appl. Sci. 10 (23), 8546(2020).
  12. Identification of five gelatins based on marker peptides from type I collagen by mass spectrum in multiple reaction monitoring mode. J Agric Food Chem. 71 (14), 5851-5860 (2023).">Yang, P., et al. Identification of five gelatins based on marker peptides from type I collagen by mass spectrum in multiple reaction monitoring mode. J Agric Food Chem. 71 (14), 5851-5860 (2023).
  13. The five "ws" for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs). Crit Rev Oncol Hematol. 89 (1), 112-128 (2014).">Lambertini, M., Del Mastro, L., Bellodi, A., Pronzato, P. The five "ws" for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs). Crit Rev Oncol Hematol. 89 (1), 112-128 (2014).
  14. Oral loratadine in the management of G-CSF-induced bone pain: A pilot study. Br J Nurs. 28 (4), S4-S11 (2019).">Duggan, C., et al. Oral loratadine in the management of G-CSF-induced bone pain: A pilot study. Br J Nurs. 28 (4), S4-S11 (2019).
  15. Clinical effects investigation of fuzheng shengxue decoction in the treatment of myelosuppression after chemotherapy. Clin J Tradit Chinese Med. 33 (03), 511-514 (2021).">H, L., Xw, H., Xl, Y., M, Y., Zw, Z. Clinical effects investigation of fuzheng shengxue decoction in the treatment of myelosuppression after chemotherapy. Clin J Tradit Chinese Med. 33 (03), 511-514 (2021).
  16. Analysis of Professor Zheng Yuling's medication rule for ovarian cancer. Mod Tradit Chinese Med. 42 (06), 73-81 (2022).">L, C., Yl, Z. Analysis of Professor Zheng Yuling's medication rule for ovarian cancer. Mod Tradit Chinese Med. 42 (06), 73-81 (2022).
  17. Evaluation of individual quality of life (QOL) among patients with tracheostomy using WHO-QOL BREF questionnaire. Indian J Otolaryngol Head Neck Surg. 74 (Suppl 3), 5207-5216 (2022).">Kumar, V., Malhotra, V., Sinha, V. Evaluation of individual quality of life (QOL) among patients with tracheostomy using WHO-QOL BREF questionnaire. Indian J Otolaryngol Head Neck Surg. 74 (Suppl 3), 5207-5216 (2022).
  18. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 6 (13), (2014).">Ru, J., et al. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 6 (13), (2014).
  19. Etcm: An encyclopaedia of traditional Chinese medicine. Nucleic Acids Res. 47 (D1), D976-D982 (2019).">Xu, H. Y., et al. Etcm: An encyclopaedia of traditional Chinese medicine. Nucleic Acids Res. 47 (D1), D976-D982 (2019).
  20. Pubchem 2019 update: Improved access to chemical data. Nucleic Acids Res. 47 (D1), D1102-D1109 (2019).">Kim, S., et al. Pubchem 2019 update: Improved access to chemical data. Nucleic Acids Res. 47 (D1), D1102-D1109 (2019).
  21. Swisstargetprediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 47 (W1), W357-W364 (2019).">Daina, A., Michielin, O., Zoete, V. Swisstargetprediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res. 47 (W1), W357-W364 (2019).
  22. Nucleic Acids Res. 46 (5), 2699(2018).">The Uniprot Consortium. Uniprot: The universal protein knowledgebase. Nucleic Acids Res. 46 (5), 2699(2018).
  23. The GeneCards Suite: From gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics. 54, 31.30.33-1.30.31 (2016).">Stelzer, G., et al. The GeneCards Suite: From gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics. 54, 31.30.33-1.30.31 (2016).
  24. Searching online Mendelian Inheritance in Man (OMIM): A knowledgebase of human genes and genetic phenotypes. Curr Protoc Bioinformatics. 58, 1.2.1-1.2.12 (2017).">Amberger, J. S., Hamosh, A. Searching online Mendelian Inheritance in Man (OMIM): A knowledgebase of human genes and genetic phenotypes. Curr Protoc Bioinformatics. 58, 1.2.1-1.2.12 (2017).
  25. The string database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45 (D1), D362-D368 (2017).">Szklarczyk, D., et al. The string database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45 (D1), D362-D368 (2017).
  26. Effect of a total extract and saponins from Astragalus glycyphyllos l. On human coronavirus replication in vitro. Int J Mol Sci. 24 (22), 16525(2023).">Hinkov, A., et al. Effect of a total extract and saponins from Astragalus glycyphyllos l. On human coronavirus replication in vitro. Int J Mol Sci. 24 (22), 16525(2023).
  27. Integrative pharmacology reveals the mechanisms of erzhi pill, a traditional chinese formulation, against diabetic cardiomyopathy. J Ethnopharmacol. 296, 115474(2022).">Peng, M., et al. Integrative pharmacology reveals the mechanisms of erzhi pill, a traditional chinese formulation, against diabetic cardiomyopathy. J Ethnopharmacol. 296, 115474(2022).
  28. Spatholobi caulis: A systematic review of its traditional uses, chemical constituents, biological activities, and clinical applications. J Ethnopharmacol. 317, 116854(2023).">Pan, Y., Luo, X., Gong, P. Spatholobi caulis: A systematic review of its traditional uses, chemical constituents, biological activities, and clinical applications. J Ethnopharmacol. 317, 116854(2023).
  29. The clinical value of huangqi injection in the treatment of leucopenia: A meta-analysis of clinical controlled trials. PLoS One. 8 (12), e83123(2013).">Zhang, C., et al. The clinical value of huangqi injection in the treatment of leucopenia: A meta-analysis of clinical controlled trials. PLoS One. 8 (12), e83123(2013).
  30. Aidi injection plus platinum-based chemotherapy for stage IIIB/IV non-small cell lung cancer: A meta-analysis of 42 RCTs following the PRISMA guidelines. J Ethnopharmacol. 221, 137-150 (2018).">Wang, J., et al. Aidi injection plus platinum-based chemotherapy for stage IIIB/IV non-small cell lung cancer: A meta-analysis of 42 RCTs following the PRISMA guidelines. J Ethnopharmacol. 221, 137-150 (2018).
  31. Cytokines and growth factors. Adv Biochem Eng Biotechnol. 171, 87-113 (2020).">Silva, A. C., Lobo, J. M. S. Cytokines and growth factors. Adv Biochem Eng Biotechnol. 171, 87-113 (2020).
  32. Tumor necrosis factor-alpha and interleukin-6 regulate secretion of brain-derived neurotrophic factor in human monocytes. J Neuroimmunol. 160 (1-2), 204-209 (2005).">Schulte-Herbrüggen, O., et al. Tumor necrosis factor-alpha and interleukin-6 regulate secretion of brain-derived neurotrophic factor in human monocytes. J Neuroimmunol. 160 (1-2), 204-209 (2005).
  33. Alternative splicing of Vegfa is regulated by RBM10 in endometrial cancer. Kaohsiung J Med Sci. 36 (1), 13-19 (2020).">Dou, X. Q., et al. Alternative splicing of Vegfa is regulated by RBM10 in endometrial cancer. Kaohsiung J Med Sci. 36 (1), 13-19 (2020).
  34. Etv6 activates Vegfa expression through positive and negative transcriptional regulatory networks in Xenopus embryos. Nat Commun. 10 (1), 1083(2019).">Li, L., Rispoli, R., Patient, R., Ciau-Uitz, A., Porcher, C. Etv6 activates Vegfa expression through positive and negative transcriptional regulatory networks in Xenopus embryos. Nat Commun. 10 (1), 1083(2019).
  35. Vegf regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature. 417 (6892), 954-958 (2002).">Gerber, H. P., et al. Vegf regulates haematopoietic stem cell survival by an internal autocrine loop mechanism. Nature. 417 (6892), 954-958 (2002).
  36. Adaptation of endothelial cells to physiologically-modeled, variable shear stress. PLoS One. 8 (2), e57004(2013).">Uzarski, J. S., Scott, E. W., Mcfetridge, P. S. Adaptation of endothelial cells to physiologically-modeled, variable shear stress. PLoS One. 8 (2), e57004(2013).
  37. Direct inhibition of tnf-α promoter activity by Fanconi anemia protein FANCD2. PLoS One. 6 (8), e23324(2011).">Matsushita, N., et al. Direct inhibition of tnf-α promoter activity by Fanconi anemia protein FANCD2. PLoS One. 6 (8), e23324(2011).
  38. Based on hematopoietic regulatory network and data mining to explore the synergistic mechanism of carica papaya leaf in the treatment of anemia. , Guangdong Pharmaceutical University. Guangzhou. (2021).">Lh, J. Based on hematopoietic regulatory network and data mining to explore the synergistic mechanism of carica papaya leaf in the treatment of anemia. , Guangdong Pharmaceutical University. Guangzhou. (2021).
  39. Src-3 is involved in maintaining hematopoietic stem cell quiescence by regulation of mitochondrial metabolism in mice. Blood. 132 (9), 911-923 (2018).">Hu, M., et al. Src-3 is involved in maintaining hematopoietic stem cell quiescence by regulation of mitochondrial metabolism in mice. Blood. 132 (9), 911-923 (2018).
  40. Resveratrol antagonizes bone marrow suppression in ionizing radiation mice via Jak2/Stat3 pathway. , Nanhua University. Hengyang. (2020).">R, W. Resveratrol antagonizes bone marrow suppression in ionizing radiation mice via Jak2/Stat3 pathway. , Nanhua University. Hengyang. (2020).
  41. Proanthocyanidin a1 promotes the production of platelets to ameliorate chemotherapy-induced thrombocytopenia through activating the Jak2/STAT3 pathway. Phytomedicine. 95, 153880(2022).">Wang, R., et al. Proanthocyanidin a1 promotes the production of platelets to ameliorate chemotherapy-induced thrombocytopenia through activating the Jak2/STAT3 pathway. Phytomedicine. 95, 153880(2022).
  42. Interleukin (il-6) immunotherapy. Cold Spring Harb Perspect Biol. 10 (8), a028456(2018).">Tanaka, T., Narazaki, M., Kishimoto, T. Interleukin (il-6) immunotherapy. Cold Spring Harb Perspect Biol. 10 (8), a028456(2018).
  43. Recent studies on PI3K/AKT/mTOR signaling pathway in hematopoietic stem cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 21 (01), 245-249 (2013).">Yc, Z., T, C., Wp, Y. Recent studies on PI3K/AKT/mTOR signaling pathway in hematopoietic stem cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 21 (01), 245-249 (2013).
  44. Hypoxia regulates the hematopoietic stem cell niche. Pflugers Arch. 468 (1), 13-22 (2016).">Morikawa, T., Takubo, K. Hypoxia regulates the hematopoietic stem cell niche. Pflugers Arch. 468 (1), 13-22 (2016).
  45. Regulation of hypoxia-inducible gene expression after HIF activation. Exp Cell Res. 356 (2), 182-186 (2017).">Suzuki, N., Gradin, K., Poellinger, L., Yamamoto, M. Regulation of hypoxia-inducible gene expression after HIF activation. Exp Cell Res. 356 (2), 182-186 (2017).
  46. Erythrocytosis: The hif pathway in control. Blood. 122 (7), 1122-1128 (2013).">Franke, K., Gassmann, M., Wielockx, B. Erythrocytosis: The hif pathway in control. Blood. 122 (7), 1122-1128 (2013).
  47. Th17/treg-cell balance in the peripheral blood of pregnant females with a history of recurrent spontaneous abortion receiving progesterone or cyclosporine a. Exp Ther Med. 21 (1), 37(2021).">Wang, S., et al. Th17/treg-cell balance in the peripheral blood of pregnant females with a history of recurrent spontaneous abortion receiving progesterone or cyclosporine a. Exp Ther Med. 21 (1), 37(2021).
  48. Cell cycle and differentiation of sca-1(+) and sca-1(-) hematopoietic stem and progenitor cells. Cell Cycle. 17 (16), 1979-1991 (2018).">Páral, P., et al. Cell cycle and differentiation of sca-1(+) and sca-1(-) hematopoietic stem and progenitor cells. Cell Cycle. 17 (16), 1979-1991 (2018).
  49. marrow-derived stem cell populations are differentially regulated by thyroid or/and ovarian hormone loss. Int J Mol Sci. 18 (10), 2139(2017).">Mogharbel, B. F., et al. marrow-derived stem cell populations are differentially regulated by thyroid or/and ovarian hormone loss. Int J Mol Sci. 18 (10), 2139(2017).

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Peanut Skin DecoctionLung CancerMyelosuppression PreventionChemotherapy ImmunotherapySquamous Cell CarcinomaGranulocyte Colony Stimulating FactorWhite Blood Cell CountQuality Of LifeNetwork PharmacologySignaling Pathways
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