Background: A diabetic foot ulcer (DFU) is a serious, long-term condition associated with a significant risk of disability and mortality. However, research on its biomarkers is still limited. This study utilizes bioinformatics and machine learning methods to identify immune-related biomarkers for DFU and validates them through external datasets and animal experiments. Methods: This study used bioinformatics and machine learning to analyze microarray data from the Gene Expression Omnibus (GEO) database to identify key genes associated with DFU. Animal experiments were conducted to validate these findings. This research employs the datasets GSE68183 and GSE80178 retrieved from the GEO database as the training dataset for building a gene machine learning model, and after conducting differential analysis on the data, this study used package glmnet and package e1071 to construct LASSO and SVM-RFE machine learning models, respectively. Subsequently, we validated the model using the training set and validation set (GSE134431). We conducted enrichment analysis, including GSEA and GSVA, on the model genes. We also performed immune functional analysis and immune-related analysis on the model genes. Finally, we conducted immunohistochemistry (IHC) validation on the model genes. Results: This study identifies GSTM5 as a potential immune-related key target in DFU using machine learning and bioinformatics methods. Subsequent validation through external datasets and IHC experiments also confirms GSTM5 as a critical biomarker for DFU. The gene may be associated with T cells regulatory (Tregs) and T cells follicular helper, and it influences the NF-κB, GnRH, and MAPK signaling pathway. Conclusion: This study identified and validated GSTM5 as a biomarker for DFU. This finding may potentially provide a target for immune therapy for DFU.

Doxorubicin (DOX)-induced cardiotoxicity (DIC) injury primarily contributes to anthracycline-associated end-stage cardiovascular mortality. Ligustrazine (LIG), a natural compound extracted from Ligusticum chuanxiong, a medicinal plant, has cardioprotective effects. However, therapeutic applications of LIG are limited owing to its poor water solubility, rapid degradation, and low bioavailability. These limitations can be overcome by encapsulating LIG into nanocarriers. We highlight the therapeutic potential of LIG drug delivery technology (LIG–Na) for DIC by integrating bioinformatics, single-cell sequencing, spatial transcriptomics, and transgenic animal models, and investigate the mechanisms underlying mitochondrial homeostasis (MQH). We used bioinformatics to predict DIC-related mechanisms and established DOX-induced models using SIRT5/DUSP1/PHB2CKO mice and DUSP1 transgenic mice (SIRT5/DUSP1/PHB2TG). The pathological mechanisms of LIG-Na-mediated alleviation of cardiac injury were examined using echocardiography, WB, TEM, and fluorescence staining. In addition, mitochondrial functional and morphological changes were evaluated using qPCR, ELISA, and confocal laser scanning microscopy following si/adRNA-mediated silencing of SIRT5/DUSP1/PHB2 in cardiomyocytes to further assess the targeted therapeutic effects of LIG–Na. DOX treatment induced severe mitochondrial dysfunction, which was effectively normalized by LIG–Na. Although these protective effects were completely abolished in SIRT5/DUSP1/PHB2CKO mice, these remained unaffected in SIRT5/DUSP1/PHB2TG mice. LIG-Na ameliorated DOX-mediated cardiac dysfunction and MQH dysregulation through the SIRT5/DUSP1-PHB2S91 phosphorylation axis, thereby effectively suppressing mitochondrial dysfunction and mitigating DIC in mice.

Objective. This meta-analysis aims to evaluate the effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) in treating post-operative pain. Methods. This meta-analysis was registered in PROSPERO (CRD42021286753). We searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials (RCTs) about TEAS in treating postoperative pain that were published before November 2021. The primary outcome was visual analogue scale (VAS) within 24h after surgery. The secondary outcomes included postoperative opioid analgesic drug consumption and the occurrence of adverse reactions within the postoperative 2472h. Adverse reactions included dizziness, nausea, and vomiting. Continuous variables were analyzed using mean difference (MDs) or standardized mean difference (SMDs) and 95 CIs. Relative risk (RR) and 95 CI were used for dichotomous data. The data were pooled and analyzed by RevMan 5.4 and STATA15.0 software. Results. Seventeen trials with 1375 participants were included. The current results suggested that application of TEAS showed obvious superiority in reducing VAS scores (SMD=1.51, 95 CI=2.200.82, I2=96). Subgroup analysis was performed according to open surgery and minimally invasive surgery. VAS scores were decreased after surgery at 24h (SMD=0.84, 95 CI=1.070.6, I2=96; SMD=0.88, 95 CI=1.020.75, I2=96). The incidence of postoperative dizziness and nausea and vomiting was significantly lower in the TEAS group within postoperative 2472h (RR=0.48, 95 CI=0.340.68, I2=0; RR=0.66, 95 CI=0.441.01, I2=69; and RR=0.49, 95 CI=0.241.00, I2=51). Postoperative opioid analgesics were also reduced in the TEAS group within 72h after surgery (SMD=2.10, 95 CI=3.370.82, I2=96). Conclusions. TEAS can reduce postoperative pain as well as the incidence of dizziness, nausea, and vomiting and the number of analgesics used after surgery. TEAS is a reasonable modality to incorporate into a multimodal management approach for postoperative pain.

Objectives. Diabetic foot ulcer (DFU) is one of the devastating complications of diabetes. It has high mortality and disability rates. The number of research articles on DFUs has increased. This study was designed to explore the global trends and research hotspots of DFUs to benefit researchers in shaping future research directions. Methods. Literatures relating to DFU from 2004 to 2020 were retrieved from the Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). The current status of DFU research (including publications, journals, the performances of relevant countries, institutions, and authors and the research trends and hotspots of DFU) was analyzed with the WoSCC. VOSviewer v1.6.10.0 was utilised for cocitation, coauthorship, cooccurrence analyses, and bibliographic coupling. Results. A total of 5869 publications on DFUs were retrieved. We performed a longitudinal review of publications over 17 years: 4500 articles and 865 review articles on DFUs published from 2004 to 2020 were analyzed. The total citation was 107,296. The USA ( ), England ( ), and China ( ) were the three largest contributors. The University of Washington had the greatest number of publications within this time period ( ), and it had the most cooperative units and was in the core position in all research institutions, followed by the University of Manchester ( ) and the University of Miami ( ). Armstrong DG (91/1.69%) and Lavery LA (55/1.19%) should be regarded as scholars who have made outstanding contributions. The top journal with the greatest total link strength was Diabetes Care. Analysis showed that the global research hotspots of DFU focused on lower limb amputation, diabetic foot infection, and treatment and management of DFU. Studies on osteomyelitis, wound therapy and management, multidisciplinary integration and mechanism of DFUs, and its related diseases are the research fronts that should be closely watched in the future. Conclusions. This study revealed the current research status and hotspots in the domain of DFU over the past 17 years, which can help researchers to further pinpoint potential perspectives on hot topics and research frontiers.

Electrical stimulation (ES) is considered a promising therapy for chronic wounds via conductive dressing. However, the lack of a clinically suitable conductive dressing is a serious challenge. In this study, a suitable conductive biomaterial with favorable biocompatibility and conductivity was screened by means of an inherent structure derived from the body based on electrical conduction in vivo. Ions condensed around the surface of the microtubules (MTs) derived from the cell’s cytoskeleton are allowed to flow in the presence of potential differences, effectively forming a network of biological electrical wires, which is essential to the bioelectrical communication of cells. We hypothesized that MT dressing could improve chronic wound healing via the conductivity of MTs applied by ES. We first developed an MT-MAA hydrogel by a double cross-linking method using UV and calcium chloride to improve chronic wound healing by ES. In vitro studies showed good conductivity, mechanical properties, biocompatibility, and biodegradability of the MT-MAA hydrogel, as well as an elevated secretion of growth factors with enhanced cell proliferation and migration ability in response to ES. The in vivo experimental results from a full-thickness diabetic wound model revealed rapid wound closure within 7d in C57BL/6J mice, and the wound bed dressed by the MT-MAA hydrogel was shown to have promoted re-epithelization, enhanced angiogenesis, accelerated nerve growth, limited inflammation phases, and improved antibacterial effect under the ES treatment. These preclinical findings suggest that the MT-MAA hydrogel may be an ideal conductive dressing for chronic wound healing. Furthermore, biomaterials based on MTs may be also promising for treating other diseases.