Abstract：
Diabetic foot ulcers (DFUs) often develop into hard-to-heal wounds due to complex factors. Several biomarkers capable of identifying those at risk of delayed wound healing have been reported. Controlling or targeting these biomarkers could prevent the progression of DFUs into hard-to-heal wounds. This scoping review aimed to identify the key biomarkers that can predict hard-to-heal DFUs. Studies that reported biomarkers related to hard-to-heal DFUs, from 1980 to 2023, were mapped. Studies were collected from the following databases: MEDLINE, CINAHL, EMBASE, and ICHUSHI (Japana Centra Revuo Medicina), search terms included \"diabetic,\" \"ulcer,\" \"non-healing,\" and \"biomarker.\" A total of 808 articles were mapped, and 14 (10 human and 4 animal studies) were included in this review. The ulcer characteristics in the clinical studies varied. Most studies focused on either infected wounds or neuropathic wounds, and patients with ischemia were usually excluded. Among the reported biomarkers for the prediction of hard-to-heal DFUs, the pro-inflammatory cytokine CXCL-6 in wound fluid from non-infected and non-ischemic wounds had the highest prediction accuracy (area under the curve: 0.965; sensitivity: 87.27%; specificity: 95.56%). CXCL-6 levels could be a useful predictive biomarker for hard-to-heal DFUs. However, CXCL6, a chemoattractant for neutrophilic granulocytes, elicits its chemotactic effects by combining with the chemokine receptors CXCR1 and CXCR2, and is involved in several diseases. Therefore, it\'s difficult to use CXCL6 as a prevention or treatment target. Targetable specific biomarkers for hard-to-heal DFUs need to be determined.
摘要：
由于复杂的因素，糖尿病足溃疡（DFU）通常会发展为难以愈合的伤口。已经报道了几种能够鉴定有延迟伤口愈合风险的生物标志物。控制或靶向这些生物标志物可以防止DFU进展为难以愈合的伤口。这项范围审查旨在确定可以预测难以治愈的DFU的关键生物标志物。研究报告了与难以治愈的DFU相关的生物标志物，从1980年到2023年，都是地图。研究来自以下数据库：MEDLINE，CINAHL,EMBASE,和ICHUSHI(JapanaCentraRevuoMedicina)，搜索词包括“糖尿病，\"\"溃疡,\"\"不愈合,\"和\"生物标记。“总共绘制了808篇文章，14项(10项人类研究和4项动物研究)纳入本综述。临床研究中的溃疡特征各不相同。大多数研究集中在感染伤口或神经性伤口上，缺血患者通常被排除在外。在报道的用于预测难以治愈的DFU的生物标志物中，来自未感染和非缺血性伤口的伤口液中的促炎细胞因子CXCL-6具有最高的预测准确性(曲线下面积:0.965;敏感性:87.27%;特异性:95.56%).CXCL-6水平可能是难以治愈的DFU的有用预测生物标志物。然而,CXCL6，一种嗜中性粒细胞的化学引诱物，通过与趋化因子受体CXCR1和CXCR2结合引起其趋化作用,并且涉及多种疾病。因此,很难将CXCL6作为预防或治疗靶点。需要确定难以治愈的DFU的可靶向特异性生物标志物。
