The cutaneous lymphatic system regulates tissue inflammation, fluid balance and immunological responses. Lymphangiogenesis or lymphatic dysfunction may lead to lymphedema, immune deficiency, chronic inflammation etc. Tissue regeneration and healing depend on angiogenesis and lymphangiogenesis during wound healing. Tissue oedema and chronic inflammation can slow wound healing due to impaired lymphangiogenesis or lymphatic dysfunction. For example, impaired lymphangiogenesis or lymphatic dysfunction has been detected in nonhealing wounds such as diabetic ulcers, venous ulcers and bedsores. This review summarizes the structure and function of the cutaneous lymphatic vessel system and lymphangiogenesis in wounds. Furthermore, we review wound lymphangiogenesis processes and remodelling, especially the influence of the inflammatory phase. Finally, we outline how to control lymphangiogenesis to promote wound healing, assess the possibility of targeting lymphangiogenesis as a novel treatment strategy for chronic wounds and provide an analysis of the possible problems that need to be addressed.

Objective: This study evaluated the efficacy of various local management strategies for diabetic foot ulcers (DFUs). Background: Several surgical and nonsurgical local interventional approaches are available for the treatment of DFUs. The comparative effectiveness of different treatments is unknown, and it remains unclear which approach is the optimal choice for DFU treatment due to limited direct comparisons. Methods: We did a systematic review and meta-analysis to select the optimal approach to DFU's local management. We searched Medline, Embase, Web of Science, and ClinicalTrials.gov from inception to September 1, 2023, to identify relevant randomized controlled trials. We analyzed data by pairwise meta-analyses with a random-effects model. A network meta-analysis using the surface under the cumulative ranking curve was performed to evaluate the comparative efficacy of different interventional approaches in the early (within 12 wk) and late stages (over 12 wk). Results: In all, 141 randomized controlled trials involving 14076 patients and exploring 14 interventional strategies were eligible for inclusion. Most studies (102/141) had at least 1 risk-of-bias dimension. Good consistency was observed during the analysis. Local pairwise comparisons demonstrated obvious differences in the early-stage healing rate and early-stage and late-stage healing times, while no significant difference in the late-stage healing rate or adverse events were noted. surface under the cumulative ranking curves identified the standard of care (SOC) + decellularized dressing (DD), off-loading (OL), and autogenous graft (AG) as the 3 most effective interventions within 12 weeks for both healing rate (97%, mean rank: 1.4; 90%, mean rank: 2.3; 80.8%, mean rank: 3.5, respectively) and healing time (96.7%, mean rank: 1.4; 83.0%, mean rank: 3.0; 76.8%, mean rank: 3.8, respectively). After 12 weeks, local drug therapy (LDT) (89.5%, mean rank: 2.4) and OL (82.4%, mean rank: 3.3) ranked the highest for healing rate, and OL (100.0%, mean rank: 1.0) for healing time. With respect to adverse events, moderate and high risks were detected in the SOC + DD (53.7%, mean rank: 7.0) and OL (24.4%, mean rank: 10.8) groups, respectively. Conclusion: The findings suggest that OL provided considerable benefits for DFU healing in both the early and late stages, but the high risk of adverse events warrants caution. SOC+DD may be the preferred option in the early stages, with an acceptable risk of adverse events.

IL-17, a pleiotropic cytokine, activates downstream signaling pathways through the IL-17 receptor (IL-17R), influencing the expression and regulation of inflammatory mediators, growth factors, and matrix metalloproteinases, thereby modulating various biological processes. Recent studies have shown that IL-17 exhibits dynamic biphasic effects during tissue repair: in the acute phase, it accelerates tissue repair by promoting epithelial regeneration, angiogenesis, and the recruitment of reparative immune cells, whereas in the chronic phase, excessive activation leads to uncontrolled inflammation and fibrosis progression. This “double-edged sword” effect shows significant heterogeneity across different tissues, including the skin, lungs, and intestines. Despite the widely recognized dual roles of IL-17, the field still lacks a holistic perspective that systematically explains how this duality is regulated across different tissue environments. This review outlines recent advances in IL-17’s functional dichotomy and identifies cellular origin, injury phase, and local microenvironment as critical regulatory determinants. We aim to elucidate under what circumstances and why IL-17 promotes tissue repair rather than exacerbates fibrosis, and discuss the implications of these insights for developing therapeutic strategies tailored to distinct clinical scenarios.

Objective: There is no consensus on the efficacy and safety of nerve decompressive surgery of lower limbs (NDSLL) for diabetic peripheral neuropathy (DPN). This systematic review aims to evaluate the efficacy and safety of NDSLL compared with no surgery in DPN by analyzing relevant evidence from randomized controlled trials (RCTs). Methods: Using PubMed, Embase, Cochrane Library, ClinicalTrials.org and Chictr.org.cn, a systemic literature review was performed in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement (CRD42021295459). Results: Screening filtered 793 studies to 7 trials containing 207 patients. Only two of the eight registered RCTs have been published (25% publication rate), indicating substantial publication bias. Risk of bias was high across most trials, with particular concerns regarding: lack of participant and personnel blinding; absence of sham surgery controls in 6/7 trials; incomplete outcome data; and selective reporting. These methodological flaws likely contribute to overestimation of treatment effects. Compared to no surgery, NDSLL was associated with VAS reduction at postoperative month (POM) 6 (WMD: −2.77, 95% CI: −3.84 to −1.69) and POM 12 (WMD: −2.41, 95% CI: −4.52 to −0.29). However, wide confidence intervals—particularly at 12 months—and high bias risk limit confidence in these estimates. No RCT evidence supported improvement in quality of life, nerve conduction velocity, balance, ulcer healing, or sensation. Among 113 NDSLL patients, 27 (23.9%) experienced wound-related complications (infection, dehiscence, edema, hematoma); no complications were reported in no-surgery groups. Conclusions: NDSLL may offer pain relief in selected DPN patients, but the current evidence is derived from a small number of high-bias RCTs with substantial publication bias, considerable methodological heterogeneity, and a notable complication rate. The true treatment effect may be substantially smaller than pooled estimates suggest. The absence of demonstrable benefit on quality of life, nerve function, balance, ulcer healing, or sensation constrains clinical utility. NDSLL should remain an investigational procedure pending adequately powered, sham-controlled, multicenter RCTs with standardized outcome measures. More high-quality research is urgently needed before NDSLL can be recommended as standard treatment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42021295459 , PROSPERO CRD42021295459.