Modified Pingwei Baohe decoction improves postoperative recovery in gastric cancer patients.

INTRODUCTION
Gastric cancer is a common malignant tumor of the digestive tract, with its incidence and mortality rates ranking among the highest globally, particularly in East Asia. According to 2020 statistics from the International Agency for Research on Cancer, gastric cancer accounts for 5.6% of global cancer incidence and up to 7.7% of cancer-related deaths[1], posing a severe threat to patients' lives and health. Radical gastrectomy is currently the primary treatment for gastric cancer; however, stomach removal reduces the body's storage capacity and disrupts the digestive tract structure[2]. A meta-analysis revealed that up to 68.8% of post-gastrectomy patients experience malnutrition[3], and analysis of surgical patient data showed that the incidence of postoperative incision-related infectious complications can reach 30%[4]. This indicates that surgical trauma and stress responses suppress immune function, increasing infection risks and resulting in a five-year survival rate of only 38%[5,6]. Therefore, effectively improving postoperative immune and nutritional status has become a critical focus of clinical research. Current Western medicine primarily employs nutritional supplements and immunomodulators to enhance postoperative recovery, but the adherence rate to nutritional supplements among post-gastrectomy patients is only 26.2%, with suboptimal therapeutic outcomes[7]. Traditional Chinese medicine (TCM) offers unique advantages in regulating gastrointestinal function and boosting immunity. TCM theory posits that post-gastrectomy patients exhibit a syndrome of "external excess and internal deficiency"[8]. Multiple studies have confirmed that TCM significantly reduces the risk of postoperative recurrence and metastasis in gastric cancer patients while markedly improving gastrointestinal dysfunction, shortening the time to resume normal diet from 11.84-8.88 days[9,10]. This demonstrates that TCM can effectively promote early recovery of gastrointestinal function in postoperative gastric cancer patients. Modified Pingwei Baohe decoction (MPBD) is composed of ingredients such as Atractylodes macrocephala (A. macrocephala), Magnolia officinalis (M. officinalis), dried tangerine peel, and Pinellia ternate (P. ternata). It has the effects of strengthening the spleen and stomach, aiding digestion, and clearing heat and drying dampness[11]. However, there is a lack of clinical research supporting the impact of modified MPBD on postoperative immune and nutritional status in gastric cancer patients. Thus, this study aims to explore the effects of MPBD on postoperative immune and nutritional status in gastric cancer patients, providing a new perspective for clinical intervention.

MATERIALS AND METHODS

General information
Fifty-five patients with gastric cancer who underwent radical proximal gastrectomy and were admitted to Hebei Provincial People's Hospital and The Fourth Hospital of Hebei Medical University from June 2023 to June 2025 were selected as the research subjects. The enrolled patients were numbered sequentially (01-55) and randomly divided into an observation group (n = 28) and a control group (n = 27) at a 1:1 ratio using computer-generated random numbers. The observation group consisted of 16 males and 12 females, aged 42-68 years (51.32 ± 6.11 years), with a body mass index (BMI) of 21-25 kg/m2 (22.43 ± 1.02 kg/m2), disease duration of 3-20 months (6.82 ± 3.14 months), and TCM syndrome differentiation including 11 cases of external pathogen invasion, 10 cases of food stagnation, and 7 cases of liver qi attacking the spleen. The control group comprised 14 males and 13 females, aged 44-68 years (51.61 ± 6.18 years), with a BMI of 21-24 kg/m2 (22.20 ± 1.05 kg/m2), disease duration of 4-20 months (6.74 ± 3.11 months), and TCM syndrome differentiation including 12 cases of external pathogen invasion, 9 cases of food stagnation, and 6 cases of liver qi attacking the spleen. No statistically significant differences were observed in baseline characteristics between the two groups (P > 0.05), indicating comparability.
The diagnostic criteria for gastric cancer[12] include: (1) Endoscopic confirmation of space-occupying lesions; and (2) Histological classification consistent with the World Health Organization classification of gastric cancer. In addition to meeting all the above conditions, at least one of the following criteria must be satisfied: (1) Endoscopic visualization of malignant ulcers, masses, or mucosal abnormalities; (2) Computed tomography/magnetic resonance imaging showing irregular gastric wall thickening > 1 cm with abnormal enhancement; and (3) Endoscopic ultrasound confirmation of tumor invasion beyond the muscularis mucosa (T1b or higher).

Inclusion criteria: (1) Diagnosis of early gastric cancer confirmed by gastroscopy and biopsy[12], meeting stage I-II criteria according to the UICC TNM staging system[13]; (2) Undergoing radical proximal gastrectomy; (3) Expected survival time ≥ 6 months; (4) Normal organ function confirmed by clinical evaluation; (5) No preoperative neoadjuvant chemotherapy or radiotherapy; and (6) Signed informed consent obtained from patients and their families. This study has been reviewed and approved by our hospital's medical ethics committee.

Exclusion criteria: (1) Presence of distant metastasis or locally advanced unresectable cases; (2) Patients with other concurrent malignancies; (3) BMI < 16 kg/m2 or serum albumin (ALB) < 25 g/L; (4) History of allergic reactions to any component of the investigational medication; (5) Women who are pregnant or breastfeeding; and (6) Patients with poor compliance.

Treatment methods
Patients in the control group received standard intravenous chemotherapy: On the first day after gastric cancer surgery, they were administered oxaliplatin (Jiangsu Hengrui Medicine Co., LTD., National Drug Approval Number: H20213313, Specification: 20 mL: 100 mg) via intravenous infusion at a dose of 130 mg/m2, along with oral capecitabine (Qilu Pharmaceutical Co., LTD., National Drug Approval No. H20133361, Specification: 500 mg/tablet) twice daily at 1500 mg per dose. This 7-day regimen constituted one complete treatment cycle, with a total of 4 cycles administered.
The observation group, based on the control group, took MPBD as the basic formula and modified it according to the specific symptoms of gastric cancer patients. The components of the basic formula include: 10 g of A. macrocephala, 10 g of M. officinalis, 10 g of dried tangerine peel, 10 g of P. ternata, 10 g of Poria cocos (P. cocos), 10 g of Forsythia, 10 g of wood fragrance, 10 g of roasted malt, 10 g of charred hawthorn, 10 g of roasted Six Shenqu, and 6 g of raw licorice. Adjust the prescription according to the patient's clinical symptoms: If the patient has severe chest pain and the pain spreads to both sides of the costal region, neem seeds and Corydalis yanhusuo can be added. If acid reflux symptoms occur, cuttlefish bones and Zhejiang Fritillaria can be added. If the patient has symptoms such as belching, nausea and vomiting, Perilla stems, Cyperi rhizoma, stir-fried white peony root and bamboo mushrooms can be added; If you feel chest tightness, you can add Allium victorialis, cinnamon twig and Trichosanthes kirilowii. If hematochezia occurs, the leaves of Platycladus orientalis (P. orientalis) and P. orientalis can be added. If the patient suffers from constipation, Huangshi and Zhishi can be enlarged. If the patient has a sallow complexion and feels weak, Codonopsis pilosula and Astragalus membranaceus can be added. Take one dose daily. Boil it in water to extract 300 mL of juice. Take it warm in two divided doses, 30 minutes before breakfast and dinner. Start from the first day of chemotherapy and take it continuously for 28 days.

Observation indicators and evaluation criteria

Laboratory indicator testing: Peripheral venous blood samples 2-3 mL were collected from all patients after overnight fasting using EDTA anticoagulant vacuum tubes before intervention and after 28 days of treatment. Samples were centrifuged at 3000 rpm for 5 minutes, and the supernatant was immediately transferred to -80 °C ultra-low temperature freezers for long-term storage. Serum levels of cytokines (IL-6, IL-4, IL-2, IL-17A, IFN-γ, TNF-α, and IL-10) were measured using BDTM CBA Human Th1/Th2/Th17 cytokine kits according to the manufacturer's protocol, with subsequent calculation of TNF-α/IL-4, TNF-α/IL-10, and IFN-γ/IL-4 ratios. Biochemical parameters were analyzed using an automated biochemistry analyzer: ALB was determined by bromocresol green method, total cholesterol (TC) by biuret method, while prealbumin (PA) was measured by immunoturbidimetric assay.

Immune function: Immunological assessment: Before intervention and after 28 days of treatment, 2 mL fasting peripheral venous blood samples were collected from all patients using EDTA anticoagulant vacuum tubes. T cell subsets (CD3+, CD4+, and CD8+) were analyzed by flow cytometry, with subsequent calculation of CD4+/CD8+ ratio. Detection of peripheral blood absolute lymphocyte count (ALC), lymphocyte percentage (LYM%), and neutrophil levels using a fully automated blood cell analyzer, with calculation of neutrophil-to-lymphocyte ratio (NLR) = neutrophils/ALC.

Nutritional status: Nutritional status was comprehensively evaluated using the CONUT scoring system[14] before intervention and after 28 days of treatment, calculated based on ALB, TC, and ALC parameters. The specific scoring criteria were: ALB concentration ≥ 35.0 g/L scored 0 points, 30.0-34.9 g/L scored 2 points, 25.0-29.9 g/L scored 4 points, and < 25.0 g/L scored 6 points; TC concentration ≥ 4.68 mmol/L scored 0 points, 3.64-4.67 mmol/L scored 1 point, 2.60-3.63 mmol/L scored 2 points, and < 2.60 mmol/L scored 3 points; ALC value ≥ 1.60 × 109/L scored 0 points, 1.20 × 10/L to 1.59 × 109/L scored 1 point, 0.80 × 10/L to 1.19 × 109/L scored 2 points, and < 0.80 × 109/L scored 3 points. The cumulative score from these three assessment dimensions ranged from 0-12 points. Based on the score ranges, patients' nutritional status was classified as: 0-1 indicating good nutrition, 2-4 suggesting mild malnutrition risk, 5-8 indicating moderate nutritional deficiency risk, and 9-12 representing severe nutritional deficiency.

Gastrointestinal function recovery: Record the time of the first bowel movement, defecation, and bowel sounds recovery for both groups of patients after 28 days of intervention.

Statistical analysis
The data analysis was conducted using SPSS 27.0 software. For continuous variables, mean ± SD is used for representation, independent sample t-test is used for inter group comparison, rate (%) is used for categorical variables, and χ2 test is used for comparison. The difference is statistically significant with P < 0.05.

RESULTS

Comparison of laboratory indicators between two groups

Comparison between groups: Before the intervention, there were no statistically significant differences (P > 0.05) in the serum cytokine levels (IL-6, IL-4, IL-2, IL-17A, IFN-γ, TNF-α, IL-10) between the observation group and the control group, indicating balanced baseline characteristics. After 28 days of intervention, the levels of all the aforementioned cytokines in the observation group were significantly lower than those in the control group (P < 0.05, Table 1). This indicates that MPBD combined with chemotherapy is superior to chemotherapy alone in suppressing the systemic inflammatory response.

Intra-group comparison: After 28 days of intervention, all cytokine levels within the observation group showed a significant decrease compared to pre-intervention levels (P < 0.001). Within the control group, while most cytokine levels also decreased significantly compared to pre-intervention levels (P < 0.05, Table 2), the IL-6 level showed no significant change (P = 0.206). This indicates that both intervention measures can modulate the inflammatory response, but the anti-inflammatory effect of the observation group is more comprehensive and consistent.

Comparison of immune function between two groups of patients

Comparison between groups: After the intervention, the observation group showed significantly higher levels of CD3+ and CD4+ T cells, CD4+/CD8+ ratio, ALC, LYM%, and TNF-α/IL-4 ratio compared to the control group, while the NLR was significantly lower (P < 0.05, Figure 1A-G). In addition, the TNF-α/IL-10 and IFN-γ/IL-4 ratios in the observation group were also significantly higher than those in the control group (P < 0.05, Figure 1H and I).

Intra-group comparison: After the intervention, both groups of patients showed significant increases in CD3+, CD4+, CD4+/CD8+ ratio, ALC, LYM%, and TNF-α/IL-4 ratio, along with a significant decrease in NLR compared to their pre-intervention levels (P < 0.05).

Comparison of nutritional status between two groups of patients

Comparison between groups: Before the intervention, there was no significant difference in the CONUT score or PA levels between the two groups (P > 0.05). After the intervention, the proportion of patients with a CONUT score > 2 in the observation group (10.71% vs 66.67%) was significantly lower than that in the control group, and the PA level (141.56 ± 37.38 mg/L vs 260.97 ± 61.84 mg/L) was also significantly lower than that in the control group (P < 0.001, Table 3).

Intra-group comparison: In the observation group, the proportion of patients at nutritional risk (CONUT score > 2) significantly decreased from 53.57% to 10.71% after the intervention (P < 0.001), and the PA level significantly decreased from 265.28 ± 52.31 mg/L to 141.56 ± 37.38 mg/L (P < 0.001). In the control group, there were no significant changes in either the nutritional risk proportion (77.78% vs 66.67%) or the PA level (265.74 ± 52.86 mg/L vs 260.97 ± 61.84 mg/L) before and after the intervention (P > 0.05, Table 4). This indicates that only the treatment regimen combined with MPBD effectively improved nutritional status.

Comparison of gastrointestinal function recovery
Patients in the observation group exhibited significantly shorter times to first flatus, bowel sound recovery, and abdominal distension relief compared to those in the control group (P < 0.05). Specific data are presented in Table 5.

DISCUSSION
Gastric cancer remains one of the leading global causes of cancer-related mortality, with China accounting for 44.21% of worldwide cases[15]. Despite surgical intervention, the 5-year survival rate for gastric cancer patients remains disappointingly low at only 20%, indicating suboptimal treatment outcomes[16]. This underscores the urgent need for comprehensive therapeutic approaches incorporating dietary modifications, pharmacological interventions, and long-term management strategies to improve patient prognosis. TCM attributes gastric cancer pathogenesis to spleen-stomach yin deficiency and gastric qi stagnation. MPBD, a classical Chinese herbal formula, is specifically indicated for food accumulation syndrome caused by improper or excessive dietary intake, demonstrating therapeutic effects in fortifying the spleen, promoting digestion, harmonizing the stomach, and regulating spleen-stomach qi dynamics[17,18]. This study therefore investigates the impact of MPBD on postoperative immune function and nutritional status in gastric cancer patients. This randomized controlled trial evaluated the effects of MPBD on immune function, inflammatory response, nutritional status, and gastrointestinal function recovery in gastric cancer patients after surgery. The results demonstrated that, compared to chemotherapy alone, MPBD combined with chemotherapy significantly improved all the aforementioned outcome measures.
Postoperative gastric cancer patients frequently experience issues such as immunosuppression, excessive inflammatory responses, and malnutrition, which severely hinder their recovery progress and long-term prognosis. In MPBD, A. macrocephala is the principal ingredient, and M. officinalis, dried tangerine peel and P. cocos are combined to achieve the effect of strengthening the spleen and harmonizing the stomach. P. ternata is used to tonify qi and benefit qi, calm upward movement and stop vomiting, while Forsythia is used to reduce swelling and disperse nodules, clear heat and detoxify. The combination of multiple prescriptions to a certain extent has the effect of clearing heat, unblocking the fu organs, detoxifying and eliminating pathogenic factors[19]. Previous studies have shown that Atractylodes can reduce the level of the inflammatory factor TNF-α in mice with lung injury caused by PM2.5 by 60.59%[20]. Moreover, in a mouse experiment[21], it was found that P. cocos could significantly reduce the TNF-α level in mice with skin lesions induced by ultraviolet B from 13.2 ng/mL to 7.25 ng/mL, indicating that the components such as Atractylodes and P. cocos in MPBD can alleviate the inflammatory response in patients with gastric cancer. The results of this study show that the levels of inflammatory factors such as IL-6, IFN-γ, and TNF-α in the observation group were significantly lower than those in the control group, indicating that Baohe decoction has a more significant effect in regulating gastrointestinal mucosal inflammation. The reason for the analysis is that the main ingredient in the modified MPBD is A. macrocephala, among which A. macrocephala is one of its main bioactive components. A. macrocephala can inhibit the phosphorylation and degradation of IκBα, thereby suppressing the NF-κB signaling pathway and reducing the synthesis and release of inflammatory factors in the body, resulting in a decrease in the levels of IL-6 and TNF-α in the body[22]. At the same time, Atractylodes extract can also alleviate mitochondrial dysfunction in cells and relieve the damage of oxidative stress to intestinal mucosa by eliminating reactive oxygen species and enhancing the activities of superoxide dismutase and GSH-Px in the body[23]; The main active component of M. officinalis, magnolol, can inhibit the NLRP3 inflammasome, block the oligomerization of ASC and the activation of caspase-1, reduce the maturation and release of IL-1β and IL-18, thereby activating the expression of STAT3 and RORγt, and enhancing the differentiation of naive CD4+ T cells into Th17. This further regulates the Th1/Th17 immune response, prevents excessive production of IFN-γ, and alleviates Th1-dominated intestinal inflammation[24]. The synergistic action of these mechanisms may form a crucial foundation for MPBD's efficacy in alleviating systemic inflammatory responses following surgery.
The study by Dong et al[25] demonstrated that Poria polysaccharides could significantly upregulate CD8+ and CD4+ T cell expression in C57/BL6 mice by up to twofold, indicating the close relationship between P. cocos components in MPBD and immune function. The results of this study demonstrate that regarding immune function, MPBD treatment significantly increased CD3+ and CD4+ T cell levels as well as the CD4+/CD8+ ratio, while also improving ALC and LYM%. These findings indicate its positive regulatory effect on cellular immune function. It is hypothesized that pachymaran may play a key role in this process, potentially by activating the NF-κB/MAPK signaling pathway to promote T-cell proliferation, thereby increasing CD3+ and CD4+ T-cell counts[26]. Concurrently, it may modulate the Th1/Th2 and Th17/Treg immune balance axes, further ameliorating immune dysfunction in patients and reducing recurrence risk[27]. Additionally, P. ternata in the formulation may inhibit gastric cancer progression and metastasis by regulating the PI3K/AKT/STAT3 signaling pathway, upregulating E-cadherin, p53, and Bax expression, and reducing N-cadherin levels[28], providing deeper mechanistic insights into MPBD's immunomodulatory effects.
Improved nutritional status represents another significant benefit of MPBD treatment. This study found that the proportion of patients with CONUT scores > 2 decreased significantly in the observation group, demonstrating MPBD's effectiveness in reducing postoperative malnutrition risk. This effect may be attributed to the multifaceted regulatory actions of components such as Crataegus pinnatifida and Chenpi on digestion and metabolism.
Hawthorn extract modulates the AMPK pathway to maintain intestinal barrier function, triples PPARγ levels, and subsequently reduces oxidative stress. It also alleviates lipid metabolism disorders by stabilizing the gut-liver axis, further promoting plasma PA synthesis to provide nutritional support for post-gastric cancer surgery patients[29,30]. Chenpi upregulates mucus production and tight junction protein expression while inhibiting the TLR4/NF-κB signaling pathway to reduce TNF-α levels. This normalizes serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and TC levels in gastric cancer patients, thereby protecting liver function, promoting anabolic processes, and maintaining systemic nutritional reserves[31].
In terms of gastrointestinal function recovery, MPBD significantly shortened the time to first flatus, bowel sound recovery, and abdominal distension relief. β-glucans from P. cocos modulate the relative abundance of Lactobacillus and Desulfovibrio, increasing short-chain fatty acid production to enhance gut health and barrier function[32,33]. P. ternata elevates superoxide dismutase activity by 46% and regulates inflammatory responses via the IL-23/JAK2/STAT3 pathway, restoring gut microbiota balance and metabolic homeostasis[34,35]. The synergistic effects of these components collectively promote the repair and functional recovery of the gastrointestinal mucosa.

CONCLUSION
In conclusion, MPBD effectively improves postoperative immune function, reduces inflammatory responses, enhances nutritional status recovery, and accelerates gastrointestinal function restoration in gastric cancer patients, providing a novel integrated traditional Chinese and Western medicine therapeutic approach for postoperative rehabilitation. However, this study has limitations including a relatively small sample size and single-center design, which may introduce bias; future research should expand the sample size and adopt multicenter collaborative designs to enhance the generalizability of the findings.

ACKNOWLEDGEMENTS
The authors would like to express their sincere gratitude to all the patients who participated in this study. We also extend our thanks to the medical and nursing staff of the Department of Gastrointestinal Surgery at Hebei Provincial People's Hospital and The Fourth Hospital of Hebei Medical University for their invaluable assistance in patient recruitment, data collection, and clinical support. We are also grateful to our colleagues from the TCM Pharmacy for their expertise in preparing the herbal decoctions. Finally, we acknowledge the statistical guidance provided by the Clinical Research Center of Hebei Provincial People's Hospital.