This clinical trial was registered with the Chinese Clinical Trial Registry (ITMCTR2025001993) and was conducted in strict accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use—Good Clinical Practice (ICH-GCP) guidelines, all applicable local and national regulations, the 2013 revision of the Declaration of Helsinki, and the Consolidated Standards of Reporting Trials (CONSORT) statement for randomized controlled trials. The study protocol was approved by the Ethics Committee of Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine (approval No. 2022-046). All participants provided written informed consent in accordance with the ethical principles of the 2013 revised Declaration of Helsinki.

Eighty patients with Wagner grade 2–4 diabetic foot ulcers (DFUs) were recruited from the inpatient wards of the Hand and Foot Surgery and Endocrinology Departments of our hospital between 1 March 2023 and 29 February 2024.

The inclusion criteria were: (1) age ≥ 18 years, fulfilment of the 1999 WHO diagnostic criteria for diabetes mellitus, and Wagner grade 2–4 DFU12; (2) clear consciousness and good treatment compliance; (3) adequate cognitive ability; and (4) provision of written informed consent.

Exclusion criteria were: (1) gestational diabetes mellitus; (2) severe cardiovascular, cerebrovascular, hepatic or renal disease; (3) inability to evaluate therapeutic efficacy or incomplete data; (4) conditions likely to influence efficacy assessment; (5) diabetic gangrene with black eschar and a high risk of skin breakdown; and (6) concomitant use of medications or interventions that conflicted with the study protocol during the treatment period.

The required sample size was estimated from previous studies and preliminary data. Assuming a clinically important 25 % difference in ulcer-area reduction between the SH + red/blue light group and the control group, with 80 % power and α = 0.05, 20 participants per arm were required (G*Power 3.1).

The CONSORT flow diagram (Figure 1A) shows screening, randomisation and analysis. Of 102 patients screened, 22 were excluded (10 did not meet the inclusion criteria, eight declined to participate, and four were receiving conflicting therapies); the remaining 80 patients were randomised equally into four groups. No participants withdrew, and all 80 were included in the final analysis.

Using a random-number table, 80 patients were assigned to four groups: control, SH, red/blue, and SH+red/blue. Allocation concealment was ensured using the sealed-envelope method: random numbers were generated by an independent statistician, sealed in opaque envelopes, and opened by nursing staff only after participant eligibility had been confirmed. All groups received the following interventions:

Additional management measures included:

Control group: Following standard nursing procedures, the ulcer surface was topically treated with human recombinant basic fibroblast growth factor gel (Nanhai Langtide Pharmaceutical Co., Ltd.; approval No. S20040053), after which it was covered with sterile gauze and secured with a bandage. The dosage was approximately 300 IU cm^-2, administered once daily for 2 weeks. If the ulcer healed earlier, the treatment was discontinued.

Red/blue-light group: In addition to routine nursing care, patients received alternating red and blue light irradiation, after which the wound was dressed with sterile gauze and a bandage. The Relami YR-580A integrated LED device emitted red light at 630–650 nm (70 mW cm^-2) and blue light at 450–470 nm (40 mW cm^-2) with a 100 % duty cycle; the irradiation field was 260 cm². The procedure comprised: (1) positioning the light source 15–20 cm above the wound while maintaining an ambient temperature of 18–22 °C and relative humidity of 50–60 %; (2) adjusting the height to ensure complete coverage of diabetic foot ulcers and wearing a protective mask; (3) exposing the wound to blue light for 10 min, followed by red light for 10 min, twice daily at ≥4-h intervals; and (4) defining one 20-min session as a treatment day, with seven consecutive sessions constituting one course, and two courses being administered.

SH-liquid group: In addition to routine nursing care, patients underwent SH-liquid fumigation. After fumigation, the wound was covered with sterile gauze and secured with a bandage. SH liquid was prepared from granules of raw Rehmannia root (25 g), safflower (25 g), Coptis chinensis (20 g), rhubarb (20 g), Imperata cylindrica (20 g), gardenia (20 g) and licorice (15 g). Each component was authenticated by TLC in accordance with the Chinese Pharmacopoeia (2020), and batch-to-batch consistency was confirmed by HPLC fingerprinting (similarity > 95 %). The granules were dissolved in 5 000 mL of hot water, cooled to 38–40 °C, and the affected foot was immersed in the solution. Patients were encouraged to drink additional warm water. Each fumigation lasted 15–20 min and was performed once daily for 14 days.

SH + red/blue-light group: After SH-liquid fumigation as described above, the wound was exposed to alternating red and blue light irradiation according to the red/blue-light protocol and then covered with sterile gauze and secured with a bandage.

The therapeutic efficacy of ulcer treatment was assessed according to the diagnostic and therapeutic guidelines of the State Administration of Traditional Chinese Medicine (TCM).

Healing time was defined as the interval between treatment initiation and the attainment of complete or partial healing as defined above. For Wagner grade 4 ulcers, healing time was calculated up to partial healing because complete epithelialization generally requires >2 weeks.

Potential adverse events (infection spread, burns, allergic reactions) were recorded daily in a dedicated case-report form. Severity was graded as mild (no intervention required), moderate (local treatment required), or severe (systemic treatment required).

Data entry was performed using Epidata 3.1 software, and statistical analysis was conducted using SPSS 23.0 software. Normality testing was performed via the Shapiro-Wilk test. Data conforming to a normal distribution were expressed as mean ± standard deviation (x±s); intra-group comparisons used the t-test, and inter-group comparisons used one-way analysis of variance followed by Tukey’s post-hoc test. Data with non-normal distribution were expressed as median (M) and interquartile range (IQR) comparisons used the Kruskal-Wallis H test. The chi-square test was used to compare categorical data between groups. Multiplicity adjustment was performed using the Bonferroni method to reduce type-I error risk. Statistical significance was defined as p < 0.05.

A CONSORT flow diagram (Figure 1A) elucidates the processes of participant screening, randomization, and analysis. A total of 80 Wagner grade 2–4 diabetic foot ulcers (DFUs) were randomly assigned to four study groups (n = 20 per group). Table 1 presents the baseline characteristics—age, sex, diabetes duration, ulcer duration, infection grade, and Wagner classification. No significant differences were detected among groups (p > 0.05), confirming their comparability. No severe adverse events were recorded. Specifically, the control group experienced three cases of mild infection spread (15 %), the red/blue group reported two cases of mild burns (10 %), the SH group had one case of mild allergic reaction (5 %), and the SH + red/blue group also recorded one mild allergic reaction (5 %). All events resolved with local treatment.

Notably, the SH + red/blue group achieved a significantly higher clinical success rate than the other groups (p = 0.002 vs control; p = 0.018 vs red/blue; p = 0.043 vs SH), as shown in Figures 1B and 1C, underscoring the potential efficacy of this treatment modality.

Prior to treatment, no significant differences were observed in ulcer scores among the four groups. After the intervention, scores decreased progressively in all groups, with the SH + red/blue group showing the lowest values at week 4 (Figure 2A). This group also demonstrated a significantly higher area-reduction rate (Figure 2B). For pain, the SH + red/blue group differed significantly from control (p = 0.019) but not from the red/blue (p = 0.352) or SH group (p = 0.881; Figure 2C). In addition, the SH + red/blue group exhibited a shorter healing time (Figure 2D) and, at week 2, the lowest bacterial load expressed as CFU·g^-1 of tissue (Figure 2E; Table 2).

Before intervention, VEGF and IL-1 levels did not differ significantly between groups. Time-course analysis revealed that VEGF concentrations increased in the SH + red/blue group at week 2 (p < 0.001 vs control; p < 0.001 vs red/blue; p < 0.001 vs SH; Figure 3A), whereas IL-1 concentrations decreased (p < 0.001 vs control; p < 0.001 vs red/blue; p = 0.002 vs SH; Figure 3B). These changes paralleled the reduction in ulcer area, suggesting a mechanistic link between VEGF up-regulation, IL-1 down-regulation, and wound healing (Table 3).