Efficacy and Safety of Medicinal Encircling Therapy for Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis

Abstract

Purpose

Diabetic foot ulcers represent a major clinical challenge due to delayed healing and high risk of complications. Medicinal encircling therapy, a traditional external treatment, has been widely used as an adjunctive intervention in clinical practice. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of medicinal encircling therapy combined with conventional treatment for diabetic foot ulcers.

Material and Methods

A comprehensive literature search was conducted across major English and Chinese databases from inception to November 1, 2025. Randomized controlled trials comparing medicinal encircling therapy plus conventional care versus conventional care alone were included. Primary and secondary outcomes related to ulcer healing, symptom improvement, inflammatory markers, pain, and adverse events were synthesized using risk ratios or mean differences with corresponding 95% confidence intervals. This systematic review was prospectively registered with PROSPERO (CRD420261299230).

Results

Fifteen randomized controlled trials were included, all of which were published in Chinese. The pooled results showed that adjunctive medicinal encircling therapy significantly improved complete ulcer healing rate compared with conventional treatment alone (RR = 1.78, 95% CI 1.39–2.28). Overall clinical response and several secondary outcomes generally favored the intervention, although heterogeneity was observed for some outcomes. No serious treatment-related adverse events were reported.

Conclusion

These findings suggest that medicinal encircling therapy may be a promising adjunctive treatment for diabetic foot ulcers; however, the certainty and generalizability of the evidence are limited by methodological shortcomings, incomplete safety reporting, and the inclusion of Chinese-language studies only. Further high-quality, multicenter randomized controlled trials are warranted.

Plain Language Summary

Diabetic foot ulcers are chronic wounds that heal slowly and may lead to infection, hospitalization, or even amputation if not properly managed. Standard treatment usually includes blood glucose control, wound cleaning, dressing changes, infection control, pressure off-loading, and improvement of blood circulation when needed. However, some ulcers still fail to heal well despite these treatments. Medicinal encircling therapy is a traditional Chinese external treatment in which herbal medicine is applied around the ulcer and surrounding skin, rather than directly into the open wound. This approach is intended to improve the local wound environment and support the healing process. In this systematic review and meta-analysis, we collected and analyzed randomized controlled trials that compared medicinal encircling therapy plus conventional treatment with conventional treatment alone in patients with diabetic foot ulcers. The results suggested that adding medicinal encircling therapy may increase the chance of complete ulcer healing and may improve some wound-related outcomes. The included studies did not report serious adverse events related to this therapy. These findings indicate that medicinal encircling therapy may be a useful adjunctive option for diabetic foot ulcer care. However, because many of the included trials had methodological limitations, small sample sizes, and incomplete safety reporting, the results should be interpreted with caution. More rigorous clinical trials are needed before firm conclusions can be made about its long-term effectiveness and safety.

Introduction

Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes mellitus and a major driver of lower-extremity amputation. It results from the combined effects of peripheral neuropathy, peripheral arterial disease, impaired host defense, and infection. Epidemiological data suggest that the lifetime risk of foot ulceration in people with diabetes may approach 25%, and DFU often represents the first step on the pathway to amputation, with substantial consequences for morbidity, mortality, and healthcare utilization.1–3 Beyond clinical outcomes, DFU imposes a considerable economic burden due to recurrent hospitalization, prolonged wound care, and high rates of recurrence and re-ulceration.4,5

Contemporary management of DFU emphasizes integrated care, including glycemic control, infection management, regular debridement and evidence-based wound care, pressure offloading, and revascularization when indicated.6,7 Despite these advances, delayed healing remains common in real-world practice. DFU healing is often impaired by persistent inflammation, bacterial burden, microvascular dysfunction, insufficient granulation tissue formation, delayed epithelialization, and an unstable periwound microenvironment. Many patients continue to experience recurrent infection, prolonged exudation, periwound edema, or poor granulation even under standardized care pathways. These challenges highlight the need for adjunctive interventions that can improve the local wound-healing environment without adding unacceptable risks or complexity to routine management.8

Traditional Chinese medicine (TCM) has long been used for chronic ulcer care, particularly through external therapies. Within the TCM framework, DFU is often categorized under conditions such as tuo ju (gangrene-like ulcerative disorders), and is commonly interpreted as a combination of underlying deficiency (eg, qi and yin) and local pathological excess (eg, blood stasis and “toxin”/damp-heat accumulation). Accordingly, treatment strategies typically aim to tonify deficiency, promote circulation, clear heat, and resolve toxin. Compared with systemic administration, external TCM therapies may achieve higher local exposure with limited systemic absorption, and have therefore attracted increasing clinical interest as adjuncts in DFU management.9–11

Medicinal encircling therapy (Guwei therapy, historically termed wei yao) is a representative external TCM approach. Different from direct wound-bed application, conventional topical dressings, or systemic pharmacological therapy, medicinal encircling therapy applies an herbal paste or plaster circumferentially around the ulcer margin and periwound skin. Clinically, it is intended to constrain the spread of local inflammation, reduce periwound edema and infiltration, improve microcirculation, and stabilize the periwound environment to support granulation and epithelialization.12,13 In recent years, multiple clinical trials have evaluated medicinal encircling therapy in addition to conventional DFU care, reporting potential benefits in wound healing outcomes. However, the available evidence remains inconsistent, partly due to variation in treatment duration, outcome definitions, and analytical approaches. In addition, prior reviews have often emphasized composite indicators such as “overall clinical response,” while clinically meaningful endpoints—particularly complete ulcer healing—have been less consistently prioritized, and several more recent randomized controlled trials have since become available.14

Therefore, we conducted an updated systematic review and meta-analysis to evaluate the effectiveness and safety of medicinal encircling therapy as an adjunct to conventional Western basic treatment for DFU. We prioritized complete ulcer healing as the primary endpoint and applied a transparent synthesis strategy for outcomes with substantial heterogeneity or non-normally distributed reporting.

Materials and Methods

Literature Search Strategy

This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 statement. A comprehensive literature search was performed in both Chinese and international databases from inception to November 1, 2025. The databases searched included CNKI, WanFang, VIP, and SinoMed, as well as PubMed, the Cochrane Library, Web of Science, and Embase.

Search strategies were developed based on the PICO framework, focusing on diabetic foot ulcer (population), medicinal encircling therapy (TCM) external therapies (intervention), conventional Western basic treatment (comparison), and ulcer healing–related outcomes (outcomes). Controlled vocabulary terms (eg, MeSH in PubMed and Emtree in Embase) were combined with free-text terms to maximize sensitivity. Boolean operators (AND, OR, NOT), truncation symbols, and field restrictions (title/abstract/keywords) were applied as appropriate for each database. The full search strategies are provided in Supplementary Appendix 1.

To minimize omission of relevant studies, reference lists of included articles and related reviews were manually screened. All records were imported into reference management software for deduplication. Literature searches and cross-checking were independently conducted by two trained reviewers.

Eligibility Criteria

Studies were included if they met the following criteria:

• 1)randomized controlled trials (RCTs) published in Chinese or English;
• 2)participants clinically diagnosed with diabetic foot ulcers (DFU), without restrictions on sex, age, ethnicity, geographic region, or disease duration;
• 3)the intervention group received medicinal encircling therapy in addition to conventional Western basic treatment (eg, glycemic control, wound debridement and care, infection control, off-loading, and vascular management), while the control group received the same conventional Western basic treatment alone, with or without guideline-recommended adjunctive local treatments, provided that medicinal encircling therapy was the only additional intervention in the experimental group;
• 4)at least one predefined clinical, inflammatory, or safety outcome was reported;
• 5)full texts were available with extractable data suitable for qualitative or quantitative synthesis.

Studies were excluded if they met the following criteria:

• 1)had obvious methodological flaws, such as inappropriate randomization or uncorrectable statistical errors;
• 2)reported incomplete or missing key outcome data that could not be extracted from the full text and could not be obtained after attempts to contact the original authors;
• 3)were duplicate publications or had overlapping datasets (eg, the same study population reported in different journals or at different times), in which case only the most complete or largest study was retained.

Given that medicinal encircling therapy is a regionally characteristic TCM external treatment and that much of the clinical evidence has been published in Chinese academic contexts, eligible postgraduate theses and conference papers were included if they met the above criteria. This approach was adopted to comprehensively capture available evidence and reduce potential publication bias.

Study Selection and Data Extraction

Two reviewers independently screened the titles and abstracts of all retrieved records according to the predefined eligibility criteria, followed by independent full-text assessment. Disagreements at any stage were resolved through discussion or consultation with a third reviewer. To reduce potential selection bias, duplicate publications and studies with potentially overlapping populations were carefully identified by comparing authorship, institution, sample size, intervention details, recruitment period, and outcome data. When multiple reports appeared to be derived from the same study population, only the most complete report or the report with the largest sample size was retained. Postgraduate theses and conference papers were also considered eligible when they met the predefined criteria, in order to reduce the risk of excluding relevant non-journal evidence.

Data were extracted independently by two reviewers using a standardized extraction form. The extracted information included authorship, publication year, study design, sample size, baseline characteristics, intervention and control details, treatment duration, outcome measures, follow-up period, and adverse events. Any discrepancies in data extraction were checked against the original articles and resolved by consensus or consultation with a third reviewer when necessary.

Risk of Bias Assessment

Risk of bias was assessed using the Cochrane Collaboration Risk of Bias tool (RoB 1),15,16 evaluating random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases.

Outcomes

The primary outcome was the complete ulcer healing rate, defined as complete epithelialization without drainage within the study-defined follow-up period. This outcome was selected as the primary endpoint because complete wound closure is a clinically meaningful and objective indicator of final ulcer repair in patients with DFU.

Secondary outcomes were selected to reflect different dimensions of ulcer healing, symptom improvement, inflammatory status, and safety. Ulcer-related secondary outcomes included overall clinical response rate, change in ulcer area, ulcer area reduction rate, and ulcer healing time. These outcomes were used to describe the wound-healing process and the speed or extent of ulcer improvement. TCM-related outcomes included local TCM syndrome response rate and TCM syndrome scores, which were included because medicinal encircling therapy is a TCM external treatment and several included trials evaluated local symptoms from a TCM perspective. Inflammatory markers, including IL-6, CRP/hs-CRP, and ESR, were considered supportive biological outcomes reflecting inflammatory burden. Pain intensity assessed by the visual analogue scale (VAS) was included as a patient-reported symptom outcome. Adverse events were extracted to evaluate the tolerability and safety of medicinal encircling therapy.

Statistical Analysis

Meta-analyses were performed using Review Manager (RevMan) version 5.4.1.17 For dichotomous outcomes, the number of events and the total number of participants in each group were extracted, and effect sizes were calculated as risk ratios (RRs) with 95% confidence intervals (CIs). The RR was calculated as the event proportion in the intervention group divided by the event proportion in the control group. For continuous outcomes reported as mean ± standard deviation (SD), effect sizes were calculated as mean differences (MDs) with 95% CIs. The MD was calculated as the mean value in the intervention group minus the mean value in the control group at the same assessment point or for the same change-from-baseline outcome. For outcomes where lower values indicated better improvement, such as ulcer area or pain intensity, a negative MD favored the intervention group.

Dichotomous outcomes were pooled using the Mantel–Haenszel method, and continuous outcomes were pooled using the inverse-variance method. Statistical heterogeneity was assessed using the chi-square test and the I² statistic. A fixed-effect model was applied when I² ≤ 50%; otherwise, a random-effects model was used. When data were reported as median with interquartile range or when outcome definitions and reporting formats were incompatible, quantitative pooling was not performed, and the findings were summarized qualitatively. Funnel plots were constructed to assess publication bias when at least ten studies were available for a given outcome.

Registration

This systematic review and meta-analysis was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420261299230.

Results

Study Selection

A total of 2,188 records were identified through database searching, including 1,345 from WanFang Database, 242 from VIP Database, 470 from the China Biology Medicine Database (SinoMed), 109 from China National Knowledge Infrastructure (CNKI), 12 from PubMed, 4 from the Cochrane Library, 4 from Web of Science, and 2 from Embase. No additional records were identified through other sources such as reference list screening or manual searches. After removing duplicates using EndNote software, 1,501 records remained for title and abstract screening.

During the title and abstract screening phase, 1,251 records were excluded due to inappropriate population (n = 312), interventions not meeting the inclusion criteria (n = 486), failure to report prespecified outcomes (n = 231), or inappropriate study design (eg, reviews, case reports, or animal studies) (n = 222). Consequently, 250 full-text articles were assessed for eligibility.

Following full-text review, 235 studies were further excluded due to non-randomized controlled trial design (n = 82), interventions not meeting the inclusion criteria (n = 67), outcomes not reported or data unavailable for extraction (n = 54), duplicate publication or overlapping data (n = 18), or other reasons (n = 14). The “other reasons” category included studies with serious methodological concerns, insufficient intervention details, insufficient treatment-duration or follow-up information, or inadequately reported data that could not support reliable extraction or synthesis.

Ultimately, 15 randomized controlled trials were included in the systematic review and were subjected to qualitative and quantitative synthesis. The study selection process is shown in the PRISMA flow diagram (Figure 1).18

Figure 1.

Flow diagram of study selection according to the PRISMA 2020 statement.18

Note: n indicates the number of records or studies at each stage.

Characteristics of Included Studies

All 15 included randomized controlled trials were published in Chinese between 2010 and 2023. A total of 921 patients with diabetic foot ulcers were enrolled, including 466 patients in the intervention groups and 455 patients in the control groups. The sample size of individual studies ranged from 48 to 86 participants.

In all studies, the intervention group received medicinal encircling therapy in addition to conventional Western basic treatment. Medicinal encircling therapy was applied externally in the form of herbal pastes or plasters circumferentially covering the ulcer margin and surrounding periwound skin. The control groups received conventional Western basic treatment, such as routine debridement, dressing changes, or wet dressings; some studies allowed additional standard local treatments, but none applied encircling therapy in the control arm. Treatment duration varied across studies, ranging from 7 to 60 days. Detailed information on sample size, intervention characteristics, treatment duration, and reported outcomes is summarized in Table 1.

Table 1.

Characteristics of the Included Randomized Controlled Trials

Author (Year)	Study Design	Sample Size (I/C)	Intervention	Control	Treatment Duration	Outcomes
He (2010)19	RCT	30/30	He’s black plaster (external application)	Routine surgical debridement and dressing change	30 days	①②
Cui (2011)20	RCT	25/23	Jinhuang powder (external application)	Rivanol, gentamicin, and insulin wet dressing	42 days	①②③
Zhang (2011)21	RCT	48/38	Eleven-herb medicinal wine (external application)	Rivanol wet dressing	7–60 days	①②
Gao (2012)22	RCT	30/30	Huofu ointment (external application)	Routine dressing change	30 days	①②
Meng (2015)23	RCT	30/30	Gypsum, rhubarb, frankincense ultrafine powder	Routine surgical dressing change	28 days	①②③
Zhang (2018)24	RCT	32/32	Eight-herb encircling plaster	Routine surgical dressing change	20 days	①②③④⑦
Li (2016)25	RCT	24/24	Oil-based herbal plaster	Routine care + gentamicin and insulin wet dressing	21 days	①②⑦
Liang (2016)26	RCT	30/30	Qingxiao encircling powder	Routine surgical dressing change	10 days	①②⑦
Zhan (2018)27	RCT	43/43	MEBO + Jinhuang powder	Routine care + MEBO	30 days	①②④
Chen (2020)28	RCT	30/30	Qingjinju powder encircling + APG	Autologous platelet gel (APG)	12 weeks or until healing	③⑦
Zhang (2020)29	RCT	29/30	Eight-herb encircling plaster	Routine surgical dressing change	21 days	①②③④⑦
Hu (2022)30	RCT	29/29	Sanhuang-Xuejie herbal plaster	Basic care + ethacridine lactate dressing	28 days	②③④⑤⑦
Qiu (2022)31	RCT	30/30	Qingju powder + APG	Routine care + APG spray	12 weeks or until healing	③
Zhao (2022)32	RCT	30/30	Erwei Baidu plaster	Routine care + recombinant bovine bFGF gel	28 days	②④⑦
Wang (2023)33	RCT	26/26	Alginate silver dressing on wound + encircling plaster	Routine care + alginate silver dressing	7 days	③④⑤⑥⑦

Note: ① Complete ulcer healing rate; ② Overall clinical response rate; ③ Other ulcer healing–related outcomes, including change in ulcer area, ulcer area reduction rate, or ulcer healing time; ④ TCM syndrome–related outcomes, including local TCM syndrome response rate and TCM syndrome score; ⑤ Inflammatory markers, including IL-6, CRP or hs-CRP, and ESR; ⑥ Pain intensity assessed using the visual analogue scale (VAS); ⑦ Adverse events.

Abbreviations: APG, autologous platelet gel; bFGF, basic fibroblast growth factor; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; hs-CRP, high-sensitivity C-reactive protein; I/C, intervention group/control group; IL-6, interleukin-6; MEBO, moist exposed burn ointment; RCT, randomized controlled trial; TCM, traditional Chinese medicine; VAS, visual analogue scale.

Risk of Bias Assessment

Based on the risk-of-bias assessment, the overall methodological quality of the included trials was rated as moderate to low. Most studies demonstrated low risk with respect to outcome data completeness and reporting transparency. However, important methodological limitations were identified in several key domains.

Approximately half of the studies did not clearly describe the method used for random sequence generation or were judged to be at high risk of bias in this domain. More than 75% of the studies did not implement or report allocation concealment, indicating a substantial risk of selection bias. Owing to the nature of the intervention, blinding of participants and personnel was not feasible in nearly all studies, and most trials also failed to report blinding of outcome assessors, increasing the risk of performance and detection bias. These limitations may have led to overestimation of treatment effects and may reduce the certainty of the evidence. Therefore, the findings of this review should be interpreted with caution (Figure 2 and 3).

Figure 2.

Risk of bias graph of the included studies.

Note: Green indicates low risk of bias, yellow indicates unclear risk of bias, and red indicates high risk of bias. Risk-of-bias domains included random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias.

Figure 3.

Risk of bias summary of the included studies.

Note: “+” indicates low risk of bias, “?” indicates unclear risk of bias, and “−” indicates high risk of bias.

Meta-Analysis Outcomes

Complete Ulcer Healing Rate (RR, Fixed-Effect Model)

Ten trials reported complete ulcer healing rate. Meta-analysis using the Mantel–Haenszel fixed-effect model demonstrated that the complete healing rate was significantly higher in the intervention group than in the control group (RR = 1.78, 95% CI 1.39–2.28, P < 0.00001). Statistical heterogeneity was minimal (χ² = 6.74, df = 9, P = 0.66; I² = 0%), indicating a high level of consistency across studies (Figure 4).

Figure 4.

Forest plot of complete ulcer healing rate.

Note: Squares indicate individual study estimates, horizontal lines indicate 95% confidence intervals, and the diamond indicates the pooled effect estimate.

Abbreviations: RR, risk ratio; CI, confidence interval; M-H, Mantel–Haenszel.

Overall Clinical Response Rate (RR, Random-Effects Model)

Twelve trials reported overall clinical response rate. Random-effects meta-analysis showed that the intervention group achieved a significantly higher overall clinical response rate compared with the control group (RR = 1.22, 95% CI 1.09–1.37, P = 0.0008). Substantial heterogeneity was observed among studies (I² = 77%) (Figure 5).

Figure 5.

Forest plot of overall clinical response rate.

Note: Squares indicate individual study estimates, horizontal lines indicate 95% confidence intervals, and the diamond indicates the pooled effect estimate.

Abbreviations: RR, risk ratio; CI, confidence interval; M-H, Mantel–Haenszel.

To explore potential sources of heterogeneity, a subgroup analysis was conducted based on treatment duration. In studies with a treatment duration of less than 28 days, no statistically significant difference was observed between groups (RR = 1.15, 95% CI 0.94–1.41, P = 0.16), and heterogeneity remained high (I² = 85%). In contrast, among studies with a treatment duration of 28 days or longer, the intervention group demonstrated a significantly higher overall clinical response rate than the control group (RR = 1.26, 95% CI 1.16–1.38, P < 0.00001), with no detectable heterogeneity (I² = 0%) (Figure 6).

Figure 6.

Subgroup analysis of overall clinical response rate according to treatment duration.

Note: Squares indicate individual study estimates, horizontal lines indicate 95% confidence intervals, and diamonds indicate subgroup or overall pooled effect estimates.

Abbreviations: RR, risk ratio; CI, confidence interval; M-H, Mantel–Haenszel.

Other Ulcer-Healing Related Outcomes

Change in Ulcer Area (MD, Random-Effects Model)

Seven studies reported outcomes related to changes in ulcer area. Of these, five studies presented continuous data as mean ± standard deviation (SD) and were eligible for quantitative synthesis, whereas two studies reported results as median with interquartile range (IQR) and were therefore summarized qualitatively.

Random-effects meta-analysis of the five studies reporting mean ± SD showed that the reduction in ulcer area was significantly greater in the intervention group than in the control group (MD = −3.89, 95% CI −7.24 to −0.54, P = 0.02). However, heterogeneity across studies was extremely high (I² = 96%), indicating substantial inconsistency among the pooled results (Figure 7).

Figure 7.

Forest plot of change in ulcer area.

Note: Squares indicate individual study estimates, horizontal lines indicate 95% confidence intervals, and the diamond indicates the pooled effect estimate.

Abbreviations: MD, mean difference; CI, confidence interval; IV, inverse variance.

The remaining two studies (Hu Meiyu, 2022; Wang Xuewan, 2023) reported ulcer area outcomes using median and interquartile range, suggesting skewed data distributions and the use of nonparametric statistical analyses. Because conversion of these data to mean ± SD would require additional assumptions and could introduce avoidable bias, these studies were not transformed or pooled. Qualitative synthesis indicated that both trials reported significant reductions in ulcer area following treatment in the intervention group, with statistically significant between-group differences favoring medicinal encircling therapy in the original analyses.

Ulcer Area Reduction Rate (%) (Descriptive Analysis)

Three studies reported the ulcer area reduction rate, defined as (baseline ulcer area − post-treatment ulcer area)/baseline ulcer area × 100%, which represents a continuous outcome reflecting the relative reduction in ulcer size. All three trials demonstrated statistically significant between-group differences favoring the intervention group.

Specifically, Chen Deqing (2020) reported an ulcer area reduction rate of 98.00 ± 1.40% in the intervention group compared with 86.00 ± 2.30% in the control group (P < 0.05). Hu Meiyu (2022) presented data as median (interquartile range), reporting values of 76.67% (72.65, 84.38%) in the intervention group versus 68.75% (60.43, 75.00%) in the control group (P < 0.05). Qiu Zijin (2022) reported mean ± SD values of 97.00 ± 1.40% in the intervention group and 83.00 ± 1.30% in the control group (P < 0.05).

Because of incompatible data reporting formats (mean ± SD versus median with interquartile range), these results were not pooled in a meta-analysis and are therefore presented as a descriptive synthesis.

Ulcer Healing Time (Qualitative Synthesis)

Three studies reported ulcer healing time. All three studies indicated a shorter healing duration in the intervention group compared with the control group; however, the magnitude of reduction varied substantially across studies. Given the small number of available studies and the presence of considerable heterogeneity (I² = 93%), quantitative pooling was not performed.

Specifically, Cui Xiaobin (2011) reported that ulcer healing time in the intervention group was approximately 8 days shorter than that in the control group. In contrast, Chen Deqing (2020) and Qiu Zijin (2022) each reported a reduction of approximately 20 days in the intervention group. Variations in baseline ulcer severity, definitions of healing, and follow-up duration across studies may have contributed to the observed inconsistency.

TCM Syndrome–Related Outcomes

Local TCM Syndrome Response Rate (RR, Random-Effects Model)

Five randomized controlled trials reported the local TCM syndrome response rate. Random-effects meta-analysis indicated a higher response rate in the intervention group than in the control group; however, the difference did not reach statistical significance (RR = 1.20, 95% CI 0.94–1.54, P = 0.14). Substantial heterogeneity was observed among studies (I² = 89%) (Figure 8).

Figure 8.

Forest plot of local TCM syndrome response rate.

Note: Squares indicate individual study estimates, horizontal lines indicate 95% confidence intervals, and the diamond indicates the pooled effect estimate.

Abbreviations: RR, risk ratio; CI, confidence interval; M-H, Mantel–Haenszel; TCM, traditional Chinese medicine.

Exploratory leave-one-out sensitivity analyses showed that the pooled effect estimate changed to some extent after exclusion of individual studies, suggesting that the overall result was sensitive to specific trials.

TCM Syndrome Score (Qualitative Synthesis)

Three studies reported changes in TCM syndrome scores. All studies showed significant improvements in both the intervention and control groups after treatment, as demonstrated by within-group comparisons (P < 0.05).

In the study by Hu Meiyu (2022), TCM syndrome scores were reported as median (interquartile range) and decreased from 14 (10, 17) to 4 (0, 6) in the intervention group, and from 14 (9, 16) to 6 (3, 10) in the control group. A statistically significant between-group difference was observed after treatment (P < 0.05). Zhao Ming (2022) reported post-treatment scores of 9.80 ± 6.99 in the intervention group and 14.77 ± 6.45 in the control group, with a significant between-group difference (P < 0.05). In contrast, Wang Xuewan (2023) reported significant reductions in TCM syndrome scores within both groups after treatment, but no statistically significant between-group difference was observed following treatment (P > 0.05).

Because different TCM syndrome assessment scales and data reporting formats were used across studies, quantitative pooling was not performed and the results were synthesized qualitatively.

Inflammatory Markers (Qualitative Synthesis)

Two studies reported changes in inflammatory markers, including interleukin-6 (IL-6), C-reactive protein (CRP or hs-CRP), and erythrocyte sedimentation rate (ESR). Due to differences in marker selection, measurement units, baseline levels, and data reporting formats, quantitative synthesis was not performed and the results were summarized qualitatively.

In the study by Hu Meiyu (2022), both the intervention and control groups showed significant within-group reductions in hs-CRP and ESR after treatment (P < 0.05). Post-treatment comparisons demonstrated significantly lower hs-CRP and ESR levels in the intervention group than in the control group (hs-CRP: P = 0.008; ESR: P = 0.042). Similarly, IL-6 levels decreased significantly after treatment in both groups, with a greater reduction observed in the intervention group. In the study by Wang Xuewan (2023), the intervention group showed significant post-treatment reductions in CRP and ESR (P < 0.01 and P = 0.001, respectively), whereas no statistically significant changes were observed in the control group. This study did not report standardized post-treatment between-group comparison statistics for inflammatory markers.

Overall, the available evidence suggests a trend toward greater reduction of inflammatory markers in patients receiving medicinal encircling therapy in addition to conventional treatment; however, heterogeneity in reporting and incomplete between-group comparisons limited quantitative synthesis.

Pain Intensity (VAS) (Qualitative Synthesis)

Only one randomized controlled trial (Wang Xuewan, 2023) reported pain intensity assessed using the visual analogue scale (VAS). Baseline VAS scores were comparable between the intervention and control groups (6.31 ± 2.20 vs 6.08 ± 2.37, respectively; P = 0.717).

After treatment, VAS scores decreased in both groups, with post-treatment values of 4.73 ± 2.13 in the intervention group and 5.00 ± 2.19 in the control group. No statistically significant between-group difference was observed after treatment (P = 0.655). However, within-group comparisons demonstrated significant reductions in pain intensity in both groups compared with baseline (both P < 0.01).

Because pain intensity was reported in only one study, quantitative synthesis was not performed and the results were summarized qualitatively.

Adverse Events

Eight studies reported information related to adverse events or safety. No serious treatment-related adverse events were reported in the included trials. Overall, medicinal encircling therapy was well tolerated. Only one study reported a mild local adverse event, consisting of one case of periwound blister formation in the intervention group, which resolved after discontinuation of medicinal encircling therapy. Several studies explicitly stated that no treatment-related adverse events occurred, whereas others provided only brief qualitative statements or did not describe safety monitoring procedures in detail.

Given the external application characteristics of medicinal encircling therapy, potential adverse events may include local skin irritation, erythema, itching, blistering, contact dermatitis, increased exudation, or discomfort around the wound. However, these events were not systematically monitored or consistently reported in most included studies. Therefore, although the available evidence did not identify serious safety concerns, the current data are insufficient to draw firm conclusions regarding the safety profile of medicinal encircling therapy. Future trials should include predefined adverse-event definitions, structured safety monitoring, and detailed reporting of local and systemic reactions.

Publication Bias

Publication bias was assessed for the complete ulcer healing rate because this outcome included ten studies and was therefore suitable for visual inspection using a funnel plot. The funnel plot showed an approximately symmetrical distribution, suggesting no obvious publication bias for this primary outcome (Figure 9). However, this result should be interpreted cautiously. Visual inspection of funnel plots is inherently subjective, and funnel plot assessment was not performed for other outcomes because fewer than ten studies were available for each of these outcomes. In addition, most included trials had relatively small sample sizes, and all were published in Chinese, which may increase the possibility of language bias or small-study effects. Therefore, although no marked publication bias was detected for the primary outcome, the potential influence of publication bias on the pooled estimates, especially for secondary outcomes, cannot be fully excluded.

Figure 9.

Funnel plot for assessment of publication bias in complete ulcer healing rate.

Note: Each circle represents an individual study. The x-axis represents the risk ratio, and the y-axis represents the standard error of the logarithm of the risk ratio [SE(log(RR))]. The vertical dashed line indicates the pooled effect estimate, and the diagonal dashed lines indicate the approximate 95% confidence limits.

Discussion

Interpretation of Core Outcomes and Sources of Heterogeneity

Based on pooled evidence from 15 randomized controlled trials, this systematic review and meta-analysis demonstrated that medicinal encircling therapy, when combined with conventional Western basic treatment—including glycemic control, wound debridement and dressing changes, infection management, and vascular optimization when indicated—significantly improves the complete healing rate of diabetic foot ulcers. Notably, heterogeneity for this primary outcome was minimal, indicating a high degree of consistency across studies. As complete ulcer healing represents a definitive and clinically meaningful “hard endpoint” reflecting final wound repair, this finding provides relatively stable and clinically interpretable evidence suggesting a potential therapeutic effect of medicinal encircling therapy, with greater clinical interpretability than surrogate outcomes such as symptom improvement or reduction in ulcer area.

For the overall clinical response rate, pooled analysis also favored the intervention; however, substantial heterogeneity was observed. This heterogeneity is clinically understandable because “overall clinical response” was a composite outcome defined differently across trials and was often based on varying combinations of ulcer area reduction, granulation tissue formation, exudation, local symptoms, and clinician judgment. In addition, treatment duration differed substantially among the included studies. The subgroup analysis based on treatment duration showed that studies with treatment courses of 28 days or longer demonstrated a more stable benefit with no detectable heterogeneity, whereas studies with shorter treatment courses showed inconsistent effects and high heterogeneity. This finding suggests that treatment duration may be an important contributor to heterogeneity and that short-term treatment may be insufficient to produce consistent wound-healing responses. Therefore, although the pooled result supports the potential benefit of medicinal encircling therapy, the clinical response rate should be interpreted with greater caution than the complete ulcer healing rate.

Interpretation of Additional Outcomes and Sources of Heterogeneity

Ulcer Healing–Related Outcomes

Beyond complete healing, this review assessed several complementary indicators of the healing process, including change in ulcer area, ulcer area reduction rate, and ulcer healing time. Across studies, these outcomes generally favored medicinal encircling therapy, suggesting a potential benefit in promoting wound contraction and accelerating repair. However, the comparability and stability of evidence for these outcomes were limited by substantial between-study heterogeneity.

The heterogeneity observed in ulcer area–related outcomes may have been driven by several clinical and methodological factors. First, baseline ulcer size and severity were not fully comparable across studies, and some trials included patients with different Wagner grades, infection status, ulcer depth, or vascular complications. These severity-related differences may have influenced complete healing, ulcer area reduction, and healing time, because more severe ulcers generally require longer treatment and more intensive wound management. Second, the timing of outcome assessment varied, ranging from short treatment periods to longer observation windows, which may have affected the magnitude of ulcer area reduction. Third, wound area measurement methods were not consistently reported, and differences in measurement tools or calculation methods may have contributed to variability. In addition, conventional basic treatment was not completely uniform across studies, including differences in debridement, dressing protocols, infection control, off-loading, and vascular management. Finally, although all studies used medicinal encircling therapy, the herbal formulations, dosage forms, application thickness, dressing frequency, and duration of treatment varied across trials. These factors may have influenced the pooled estimates and explain why area-based outcomes were less stable than the primary endpoint of complete ulcer healing.

TCM Syndrome–Related Outcomes

TCM syndrome–related outcomes were a key feature of this review, including the local TCM syndrome response rate and TCM syndrome score. Meta-analysis suggested a trend toward improvement in the local TCM syndrome response rate with adjunctive medicinal encircling therapy; however, heterogeneity was substantial, indicating limited consistency. Differences in syndrome criteria, response thresholds, and timing of assessment across studies likely contributed to this variability.

For TCM syndrome scores, only a small number of trials were available, and the scoring instruments and ranges varied markedly across studies; therefore, results were synthesized qualitatively. Although one study did not demonstrate a clear between-group advantage, the overall pattern suggested that adjunctive therapy may improve TCM symptom complexes relevant to DFU (eg, periwound redness and swelling, pain, and exudation). These findings highlight the potential clinical value of TCM syndrome outcomes in capturing symptom improvement, but also underscore the need for standardized and validated assessment systems to strengthen the interpretability and synthesis of evidence.

Inflammatory Markers and Pain as Supportive Evidence

Inflammatory markers (eg, IL-6, CRP/hs-CRP, and ESR) and pain intensity (VAS) were treated as auxiliary outcomes reflecting inflammatory burden and patient-reported symptoms. The included studies generally reported reductions in these indicators after treatment, particularly in the intervention group. However, evidence was limited by the small number of studies, heterogeneity in marker selection and reporting formats, and incomplete reporting of standardized between-group comparisons; consequently, quantitative synthesis was not feasible.

Accordingly, these outcomes primarily serve as supportive evidence that may help contextualize potential mechanisms—such as attenuation of local inflammation and alleviation of pain—through which medicinal encircling therapy could facilitate wound healing. Future trials should standardize outcome selection, measurement procedures, and statistical reporting to improve the feasibility of quantitative synthesis and strengthen mechanistic inference.

Innovation and Incremental Contribution of the Evidence

Compared with earlier systematic reviews of medicinal encircling therapy or broader TCM external treatments for DFU, the present study offers an updated synthesis by incorporating more recent randomized controlled trials and by prioritizing complete ulcer healing as the primary endpoint.34 Previous reviews frequently relied on composite measures such as overall clinical response rate and often combined heterogeneous external therapies, limiting clinical interpretability. By focusing on RCTs, this review aimed to synthesize comparative interventional evidence with relatively stronger methodological control than observational studies. In addition, the comparison between medicinal encircling therapy plus conventional Western basic treatment and conventional treatment alone was intended to clarify the adjunctive value of medicinal encircling therapy, rather than the overall effect of mixed external TCM interventions. This design helps distinguish the potential additional contribution of medicinal encircling therapy within an integrated DFU management strategy.

By emphasizing complete ulcer healing—a clinically meaningful and objectively defined outcome with low heterogeneity—and by explicitly separating outcomes unsuitable for quantitative pooling (such as skewed ulcer area data reported as median [IQR]), this review improves methodological transparency and reduces the risk of misleading aggregation. In addition, subgroup analyses based on treatment duration suggest that adequate exposure (≥28 days) may be important for achieving consistent benefit. TCM-featured outcomes were integrated as supportive evidence within a hierarchical framework that prioritizes hard clinical endpoints.

Emerging literature on topical and herbal approaches in wound care further underscores growing interest in localized therapies for DFU. Against this background, the present review contributes a focused synthesis on a distinctive encircling application strategy, which differs conceptually and practically from direct wound-bed application and may exert specific effects on periwound inflammation and microcirculation.

Limitations

Several limitations should be acknowledged. First, this review was based on published aggregate data and was therefore limited by the design, methodological quality, reporting completeness, and outcome definitions of the original trials. It could not address deficiencies in primary studies or individual patient-level modifiers. Second, the included trials were generally of moderate to low quality, with inadequate reporting of randomization, allocation concealment, and blinding, which may have introduced bias and overestimated treatment effects. Important clinical factors, including ulcer severity, infection status, glycemic control, vascular complications, off-loading, and concomitant treatments, were not consistently reported or controlled. Third, most studies were small, single-center trials, limiting generalizability. Substantial heterogeneity in interventions, co-interventions, treatment duration, and outcome definitions further limited interpretation, especially for continuous and TCM-specific outcomes. Fourth, all studies were published in Chinese, and some unpublished, ongoing, or poorly indexed studies may have been missed; therefore, language and publication bias cannot be excluded. Finally, safety and long-term outcomes were incompletely reported. Recurrence, amputation, quality of life, and delayed adverse events were rarely assessed. Thus, long-term efficacy and safety remain uncertain.

Implications for Clinical Practice and Future Research

From a clinical perspective, medicinal encircling therapy may be considered as an adjunctive option within an integrated DFU management strategy, rather than as a replacement for standard care. Its use should be based on conventional treatment, including glycemic control, wound debridement and dressing changes, infection management, pressure off-loading, and vascular assessment or intervention when indicated.1,6,7,35 Interdisciplinary collaboration among endocrinologists, wound-care specialists, vascular surgeons, nurses, rehabilitation professionals, and TCM practitioners may help optimize standard DFU care and support the standardized application of medicinal encircling therapy. The present findings suggest that adding medicinal encircling therapy may improve complete ulcer healing and some wound-related outcomes, particularly when treatment is applied for an adequate duration. However, because the certainty of evidence remains limited, clinical application should be cautious and individualized. Standardized application procedures, appropriate treatment duration, monitoring for local skin reactions, and patient adherence should be emphasized in practice. Because medicinal encircling therapy requires repeated external application and coordinated wound care, adherence to dressing changes, off-loading, glycemic control, and scheduled follow-up may influence the healing process and real-world effectiveness.

Future research should prioritize multicenter, adequately powered randomized controlled trials with rigorous randomization and allocation concealment, standardized outcome definitions (including complete healing, healing time, and area-based measures), harmonized TCM assessment instruments, and comprehensive safety evaluation. Recent studies further suggest that DFU research should extend beyond wound closure and incorporate patient-centered and technology-supported perspectives, including quality of life, functional capacity, digital wound monitoring, antimicrobial strategies, targeted delivery, and tissue repair.36,37 Psychological distress, such as anxiety or depression, may influence wound-healing outcomes indirectly by affecting pain perception, self-care behavior, adherence to off-loading and dressing changes, and follow-up participation.38,39 Because the included trials mainly assessed outcomes during treatment or shortly after treatment, the long-term effects of medicinal encircling therapy remain uncertain. Future studies should include adequate post-treatment follow-up to determine whether short-term improvements in ulcer healing translate into sustained clinical benefits. Long-term outcomes, including ulcer recurrence, re-ulceration, infection control, amputation, quality of life, functional recovery, and delayed adverse events, should be systematically assessed to clarify the real-world value and durability of medicinal encircling therapy in DFU care.

Conclusion

Current randomized controlled trial evidence suggests that medicinal encircling therapy, when added to conventional Western basic treatment, may improve the complete healing rate of diabetic foot ulcers, with relatively consistent findings for this primary outcome. Overall clinical response may also be improved, particularly when treatment is administered for at least 28 days. However, these findings should be interpreted cautiously because the included trials had methodological shortcomings, small sample sizes, mostly single-center designs, and incomplete safety reporting. Substantial heterogeneity and limited comparability were also observed for several secondary outcomes, which should therefore be regarded as supportive rather than definitive evidence. Larger, multicenter, rigorously designed randomized controlled trials with standardized outcome measures, longer follow-up, and comprehensive safety monitoring are needed to confirm these findings and clarify the role of medicinal encircling therapy in the comprehensive management of diabetic foot ulcers.

Funding Statement

This work was supported by the Clinical Research and Achievement Transformation Capacity Enhancement Pilot Project (Grant No. DZMG-ZLZX-25011).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no competing interests in this work.