The present study is a prospective, randomized controlled trial that was performed in The First Hospital of Harbin (Harbin, China). The study protocol was approved by the Ethics Committee of The First Hospital of Harbin (approval no. 20150507TFHX1). A total of 1,032 eligible patients with gastric cancer who underwent gastrectomy were recruited between May 2015 and June 2017. All patients were diagnosed with gastric cancer using imaging and pathology assessments and met the indications for radical gastrectomy. The baseline clinicopathological characteristics, including hypoproteinemia, tumor size, tumor stage and American Society of Anesthesiologists grade (27) were analyzed and are shown in Table I. After gastrectomy, patients voluntarily chose to undergo postoperative treatment and all patients provided written informed consent. All the patients were randomly assigned into two groups: The TCM nursing intervention group (TCM group; n=520) and the routine nursing intervention group (control group; n=512). Patients were assigned into these two groups using a block randomization method based on the disease status of patients with cancer (28). No differences in treatment were applied between the two groups, with the exception of the Jianpi Yangzheng decoction. The TCM used in this study was Jianpi Yangzheng decoction, which is composed of 12 types of Chinese herbal medicine (15 g Dangshen, 10 g Baizhu, 10 g Fuling, 15 g Shengyiren, 10 g Danggui, 15 g Shanyao, 10 g Muxiang, 10 g Baishao, 6 g Chenpi, 10 g Baqia, 15 g Shijianchuan and 3 g Zhigancao) (26). The raw herbs for the Jianpi Yangzheng decoction were obtained from Heilongjiang Traditional Chinese Medicine Hospital (Harbin, China). All the herbs were mixed with 500 ml sterile water and boiled for 30 min, and then the patients drunk the leachate. One dose of Jianpi Yangzheng decoction was orally administrated to the TCM group every day after gastrectomy for at least 6 months. The study flowchart is shown in Fig. 1. The duration of the postoperative hospital stay for patients after gastrectomy was recorded.

The inclusion criteria for the study were as follows: i) Patients diagnosed with gastric cancer; ii) patients aged from 25 to 70 years old; iii) patients with a life expectancy of at least 6 months; iv) patients underwent a gastrectomy; v) after gastrectomy, patients provided written informed consent to participate in the study according to the Good Clinical Practice criteria (29); and vi) a Karnofsky Performance Status score of >60 (30). The exclusion criteria were as follows: i) Patients with other cancer types; ii) pregnant or lactating women; iii) patients who were unable to swallow TCM; iv) patients with symptomatic brain metastasis or mental disorders; and v) patients with severe cardiovascular disease, chronic liver disease, kidney disease or blood disease.

To assess physical capacity, the 6-min walk test (6-MWT) (31) was performed every 2 months in the patients of each group. The test was performed in a 50-meter corridor and all patients were instructed to walk as far as possible in 6 min.

After gastrectomy, the postoperative pain scores of the patients in the two groups were evaluated every 3 days during the hospital stay (on days 0, 3, 6, 9, 12 and 15) using the 0–10 Numeric Rating Scale, with 0 representing no pain and 10 representing the worst imaginable pain (32). POCs in the patients with gastric cancer after surgery were recorded and classified according to the Clavien-Dindo (C-D) classification grade (33).

Blood samples were collected from each patient every 3 days (on days 0, 3, 6, 9, 12 and 15) to measure serum inflammatory cytokine levels. Postoperative inflammation score was determined by inflammation score, as described previously (34). Postoperative serum levels of C-reactive protein (CRP) (cat. no. ab260058), IL-1β (cat. no. ab214025), IL-6 (cat. no. ab178013), IL-8 (cat. no. ab214030), IL-10 (cat. no. ab185986) and TNF-α (cat. no. ab181421) were measured using ELISA kits (all Abcam) according to the manufacturer's instructions. CD3⁺, CD4⁺, CD8⁺, CD16⁺, CD19⁺ and CD45⁺ expression levels in peripheral T lymphocytes were analyzed using a FACS Canto II flow cytometer and FACS Diva software (BD Biosciences).

The clinical outcomes were standard measures of gastrointestinal function and included the time from the operation to the first passage of flatus, the time from the operation to the passage of the first defecation, and the number of patients who were comfortable with the intake of a semi-fluid diet as measured every 3 days (on days 0, 3, 6, 9, 12 and 15 days) during the hospitalization. The abdominal pain of each patient from the two groups was evaluated using Prince Henry Pain Scale scoring (35) (0, no pain when coughing; 1, pain only when coughing; 2, no pain when quiet, but pain with deep breathing; 3, mild and bearable pain when resting; 4, severe and unbearable pain). Abdominal distension (36) was evaluated using the following scale: 0, no sense of abdominal distension; 1, mild distension; 2, moderate abdominal distention; and 3, severe abdominal distention.

Postoperative mental status was evaluated in patients every 2 months post-surgery by clinicians for a total of 12 months. Quality of life after surgery was evaluated using the 36-Item Short Form Health Survey (SF-36) questionnaire (37). Scores in the SF-36 range from 0 to 100 (0 representing the worst and 100 the best). The Beck Depression Inventory (38) was used to assess the depression level in the patients after surgery. The Beck Depression Inventory includes 21 clinical symptoms of depression and the scores range from 5 to 63 (5–9, normal; 10–18, mild-to-moderate depression; 19–29, moderate-to-severe depression; 30–63, severe depression). Anxiety in patients with gastric cancer after surgery was determined by the State-Trait Anxiety Inventory (STAI) (39). The STAI includes separate measures of state- and trait-anxiety, which are scored as a minimum of 20 to a maximum of 80 (20–29, without anxiety; 20–30, the presence of anxiety; 31–49, an intermediate level of anxiety; 50–80, a high degree of anxiety).

Patients were followed up every 3 months during the 60-month follow up period. The overall survival time of the patients with gastric cancer after surgery was recorded from the date of surgery to death or the last follow-up. Recurrence time was defined as the time from surgery to recurrence or the last follow-up.

The safety of the TCM used in this study was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (40).

Data are expressed as the mean ± standard deviation or n (%). Data were analyzed using SPSS version 21.0 (SPSS Inc.; IBM Corp.). Unpaired Student's t-test was used to compare the data between two groups. Qualitative data were calculated using the χ² test or Fisher's test. Overall survival and recurrence were analyzed using Kaplan-Meier analysis. P<0.05 was considered to indicate a statistically significant difference.

A total of 1,032 patients with gastric cancer who underwent a gastrectomy were recruited to the present study. Patients with a mean age of 57.5 years (range, 53.2–62.8 years) were assigned into two groups: The TCM group (n=520) and the control group (n=512). There were 560 male and 472 female patients with gastric cancer. The surgical outcomes of the patients are shown in Table I. All patients received the same anesthetic drugs during the operation and underwent a gastrectomy. There were no significant differences between the two groups (all P>0.05). The study follow-up time was 60 months.

To verify the efficacy of TCM nursing intervention, hospital stay, postoperative pain and frequency of postoperative symptoms in patients were evaluated between the two groups. Patients in the TCM nursing intervention group had a shorter hospital stay and lower postoperative pain scores compared with those in the control group (both P<0.05; Fig. 2). It was observed that TCM nursing intervention decreased the use rate of opioids compared with the control group (P<0.05; Table II). Compared with the control, TCM nursing intervention significantly decreased the frequency of postoperative dizziness, vomiting, nausea, distention, diarrhea and comfort of intake of a semi-fluid diet during the hospital stay (all P<0.05; Table II).

Postoperative gastrointestinal dysfunction can cause the accumulation of secretions and gas, which will result in postoperative symptoms of gastrointestinal discomfort after gastrectomy (41). Thus, the differences in postoperative gastrointestinal dysfunction were compared between the two groups of patients with gastric cancer who underwent gastrectomy (Table III). The data revealed that TCM nursing intervention significantly decreased the time to first postoperative flatus and defecation, and the fasting time (all P<0.05). Postoperative patients in the TCM group were more comfortable with the intake of a semi-fluid diet than patients in the control group at 15 days post-surgery. Compared with the control, TCM nursing intervention significantly decreased the occurrence of abdominal pain and abdominal distension in the patients after gastrectomy (all P<0.05; Table III).

The effects of TCM nursing intervention on postoperative inflammation index were analyzed in the patients with gastric cancer who underwent gastrectomy. As shown in Fig. 3A, the patients in the TCM group exhibited lower inflammation scores than those in the control group at 6 days post-surgery. TCM nursing intervention also decreased the inflammatory cytokines levels of CRP, IL-1β, IL-6, TNF-α, IL-8 and IL-10 after gastrectomy compared with the control group during the hospital stay (Fig. 3B-G).

POCs in each patient with gastric cancer were recorded, classified according to the C-D classification grade and compared between the two groups. The characteristics of the patients in each C-D grade in the propensity score-matched cohorts are shown in Table IV. Grade I complications were present in 403 (77.5%) and 368 (71.9%) patients in the TCM and control groups, respectively. Grade II complications were recorded in 67 (13.1%) and 42 (8.1%) patients in the TCM and control groups, respectively. It was also demonstrated that 14 (2.7%) and 25 (4.9%) patients experienced grade III complications in the TCM and control groups, respectively, while patients with grade IV–VIII complications accounted for 36 (6.9%) and 77 (15.0%) patients at 12 months after surgery in the TCM and control groups, respectively.

Physical capacity and metal status were evaluated at the time of hospitalization and discharge for the two groups of patients with gastric cancer who underwent gastrectomy. The results data showed that TCM nursing intervention significantly improved clinician-rated measures of depression and anxiety during hospitalization compared with the control (all P<0.05). The quality of life of the patients after gastrectomy also increased in the TCM nursing intervention group when compared with that of the control group (all P<0.05). After 12-month discharge, the patients in the TCM group experienced less depression and anxiety, and a higher quality of life than those in the control group (all P<0.05) (Fig. 4). TCM nursing intervention also improved the postoperative physical capacity, as determined by 6-MWT (Table V). TCM nursing intervention increased the physical capacity of gastric cancer patients at 2, 4 and 6 months compared with the control (Fig. 5). After 6 months of follow-up, no significant difference in postoperative physical capacity was observed between the two groups.

It is now known that altered immune cell expression may be responsible for the low survival and poor prognosis in patients with gastric cancer after surgery (42). Thus, the immune function in patients with gastric cancer who underwent gastrectomy was compared between the two treatment groups in the present study. As shown in Table VI, CD3⁺, CD4⁺, CD8⁺, CD16⁺, CD19⁺ and CD45⁺ expression levels were recorded in peripheral T lymphocytes, and were higher in patients in the TCM group compared with those in the control group (all P<0.05). Compared with that in the control group, a significant increase in the concentration of natural killer cells and T cells was observed in patients in the TCM group (both P<0.05) (Table VI).

The survival and recurrence times in the patients with gastric cancer were recorded and compared between the two groups. The data revealed that TCM nursing intervention prolonged the survival after gastrectomy compared with the control during the 60-month follow-up period (Fig. 6A). Furthermore, the mortality rate of gastric cancer was also decreased in the patients in the TCM nursing intervention group (Fig. 6B). During the 5-year follow-up period, 65 (12.7%) patients in the control group died and 142 (27.7%) patients experienced recurrence or tumor metastasis, while only 30 (5.8%) patients died in the TCM nursing intervention group, and 88 (16.9%) patients experienced recurrence or tumor metastasis (Table VII).

The treatment-related adverse events were recorded after gastrectomy in the TCM nursing intervention group. Most of the TCM treatment-related adverse events were grade 1 or 2 according to National Cancer Institute Common Terminology Criteria (Table VIII). The cancer treatment-related adverse events of TCM included vomiting, pruritus, gastrointestinal reaction, increased alanine transaminase (ALT)/aspartate transaminase (AST) levels, fatigue, hypertension and diarrhea. No toxin-induced death was observed in any patient in the TCM nursing intervention group. Of the 55 patients affected, 20 (3.8%) had grade 3 diarrhea, 12 (2.3%) had grade 3 hypertension and 33 (6.3%) had a gastrointestinal reaction, and these patients were forced to reduce the dose of TCM.