Yan Liu

Full‐thickness skin defects involving tendon or bone exposure present significant clinical challenges owing to inadequate vascularity, which renders spontaneous wound healing unlikely. Conventional treatments using autologous flap transplantation may incur donor‐site morbidity. Dermal substitutes are employed to enhance wound bed construction and improve skin graft survival by promoting vascularization and extracellular matrix (ECM) deposition. However, currently available substitutes are predominantly composed of purified bovine‐ or porcine‐derived type I collagen and lack the bioactive components. Urinary bladder matrix (UBM), a naturally derived scaffold, contains a rich repertoire of ECM constituents that effectively promote the healing process, offering a potential novel approach for dermal regeneration. Nevertheless, human histological evidence on UBM in tendon/bone‐exposed wounds remains limited. In this study, we compared the efficacy of UBM wound matrix (ExceFil Biological Wound Matrix, ZhuoRuan Medical Technology) with that of artificial dermal substitute (Pelnac, GUNZE Medical Division) in treating extremity wounds with tendon/bone exposure in a series of six clinical cases. Clinically, both products successfully promoted wound vascularization and graft survival. Histological analysis revealed that the UBM group exhibited superior regenerative features, including enhanced fibroblast migration, collagen deposition, neovascularization, and immunomodulatory properties, with a higher rate of M2 macrophage polarization at 15 ± 2 days post‐implantation. Furthermore, RNA sequencing demonstrated that the UBM matrix significantly upregulated pathways related to cytokine‐cytokine receptor interaction and chemokine signaling, both of which modulate immune and regenerative processes within the wound microenvironment. These findings suggest that UBM biological matrix represents a promising dermal substitute for promoting regenerative healing in tendon/bone‐exposed wounds.

The intestinal barrier serves as a crucial defense in the body, and a compromised integrity can lead to systemic health issues. Intestinal macrophages, as key components of the intestinal immune system, have a profound influence on intestinal homeostasis. However, the complex mechanisms underlying interactions between the intestinal barrier and intestinal macrophages remain incompletely elucidated. This review systematically summarizes the bidirectional regulatory relationship between them. It specifically focuses on how the intestinal barrier impacts the phenotype, function, and heterogeneity of macrophages while concurrently analyzing the pivotal role of macrophages in maintaining and repairing intestinal barrier function. Furthermore, this review provides an in-depth analysis of the critical influence of this interaction on the pathogenesis and progression of various intestinal disorders and systemic diseases. By synthesizing and summarizing current research advances, this review aims to enhance the understanding of the regulatory mechanisms underlying intestinal immune homeostasis and to lay a theoretical foundation for developing novel strategies for the prevention and treatment of related diseases.

Non-healing chronic wounds with high susceptibility to infection represent a critical challenge in modern healthcare. While growth factors play a pivotal role in regulating chronic wound repair, their therapeutic efficacy is compromised in infected microenvironments. Current wound dressings inadequately address the dual demands of sustained bioactive molecule delivery and robust antimicrobial activity. In this study, we developed a sodium alginate hydrogel (termed P-SA/Ins), which incorporated polyhexamethylene biguanide (PHMB) grafting and long-acting glargine insulin loading. P-SA/Ins exhibited the favorable physicochemical performance, biocompatibility and antibacterial efficacy against both Gram-negative and Gram-positive pathogens through inhibition of bacterial proliferation and biofilm formation. Glargine insulin was applied to prolonged insulin delivery. P-SA/Ins treatment attenuated S. aureus induced pro-inflammatory cytokine cascades in macrophages. The evaluation in vivo using a rat model with S. aureus infected wound demonstrated that P-SA/Ins significantly enhanced wound healing and optimized skin barrier through antimicrobial-mediated modulation of macrophage polarization and subsequent inflammatory cytokine profiling. Our findings demonstrate that P-SA/Ins promotes wound healing and restores epidermal barrier integrity, indicating its potential as a therapeutic dressing for chronic wound healing, particularly in cases with infection risk.

Background: Huhuang (HH) decoction, a composition of seven traditional Chinese medicines, has demonstrated clinical efficacy in wound healing. However, its pharmacological foundation and potential mechanisms remain unclear. This study aimed to elucidate the mechanisms of action of HH decoction in the treatment of diabetic wounds.

Diabetic foot (DF) is a prevalent and significant complication of diabetes mellitus. The primary factors that contribute to amputation and mortality in DF patients are multifaceted and include foot deformities, ulcers, ischemia, and potential concurrent infections. To further standardize DF prevention and treatment in China, improve consistency in DF diagnosis and treatment, and promote the development of a specialized tiered care system, the Chinese Burn Association, the Yangtze River Delta Integrated Diabetic Foot Alliance, and the Editorial Committee of the Chinese Journal of Burns and Wound Repair established a multidisciplinary expert team. The team identified clinical issues concerning the diagnosis, treatment, and prevention of DF via the population, interventions, comparisons, outcomes framework, assessed the quality of relevant evidence using the Grading of Recommendations Assessment, Development and Evaluation system, and ultimately formulated a consensus titled “Practical Guidelines for the Prevention and Management of Diabetic Foot Disease in China.” The guidelines include 46 recommendations that address comprehensive medical assessment; internal medical treatments, including treatments related to blood glucose, blood pressure, and blood lipid control; antithrombotic and anti-infection therapy; perioperative risk assessment and management; surgical interventions, such as debridement, vascular reconstruction, and tissue repair; foot disease prevention; multidisciplinary collaboration; and the establishment of a hierarchical diagnosis and treatment system, with the objective of guiding clinical practice for managing DF in China.

Background: Sepsis-induced myocardial injury (SIMI) is recognized as a severe complication of sepsis which characterized by a high mortality rate. Notably, the pathophysiology of SIMI involves complex mechanisms, including dysregulation of autophagy. Exosomes contribute to crucial biological processes during sepsis， modulating autophagy processes and facilitating communication between cells. PIWI-interacting RNAs (piRNAs) are highly expressed in myocardial tissue and exert cardiovascular regulation properties. Therefore, we investigated the role of macrophage-derived exosome piRNAs, specifically piR-50971, in SIMI and their impact on autophagy through N6-Methyladenosine (m6A) modification of mTOR. Methods: A cecal ligation and puncture model was established to mimic the pathophysiological features of SIMI. Plasma exosomes were isolated and sequenced to characterize the expression of sepsis-related piRNAs. Bioinformatics analysis was employed to predict the potential regulatory mechanisms involving piR-50971. To investigate the direct interaction between piR-50971 and mTOR, a dual-luciferase reporter assay was conducted. Moreover, a methylated RNA immunoprecipitation assay was conducted to verify the involvement of piR-50971 in the m6A methylation modification of mTOR transcripts. Additionally, the m6A methylation level was assessed using dot blotting. Left ventricular ejection fraction and left ventricular fractional shortening of rats were detected by animal echocardiography. Transmission electron microscopy was used to detect autophagy flux in the myocardial tissue of rats in vivo. Cardiac enzymes were detected using a biochemical analyzer. Results: piR-50971 was identified as a key piRNA upregulated in plasma exosomes during SIMI, which was correlated with the inhibition of autophagy. Increased macrophage infiltration was observed in the myocardium of rats with SIMI. Additionally, cardiomyocytes treated with macrophage-derived exosomes exhibited impaired autophagy. RNA binding protein immunoprecipitation assay demonstrated an interaction between Wilms’ tumor 1-associated protein (WTAP) protein and mTOR mRNA. piR-50971 interacted with mTOR, leading to increased m6A modification through the regulation of WTAP and subsequent suppression of autophagy. Notably, this regulation upregulated mTOR translation, thereby inhibiting autophagy and exacerbating myocardial injury under septic conditions. In vivo experiments demonstrated that piR-50971 inhibition ameliorated myocardial injury and improved autophagy in rats with SIMI. Conclusions: Our findings reveal a novel mechanism by which macrophage-derived exosome piR-50971 contributes to SIMI by suppressing autophagy via m6A modification of mTOR. Overall, our results implicate piR-50971 as a potential target for therapeutic intervention in sepsis-related myocardial dysfunction.

The epidermis is the outermost layer of the skin and acts as the primary barrier to protect the body. Dendritic epidermal T cells (DETCs), which are specifically distributed in epidermal tissues, play a crucial role in skin immune surveillance and wound healing. DETCs are one of the most important components of the epidermis and exert a steady-state monitoring function, facilitating wound healing and tissue regeneration after skin injury. Skin wounds are often linked to other pathological conditions such as ageing, ultraviolet radiation, and metabolic diseases such as diabetes mellitus and obesity. Therefore, it is crucial to investigate how DETCs regulate themselves and the external environment during these pathological states. DETCs interact closely with keratinocytes in the epidermis, and this intercellular interaction may be essential for maintaining health and integrity. In this review, we focus on the characteristics and underlying mechanisms of DETCs in maintaining epidermal homeostasis and re-epithelialization in different pathological states.