Daping Hospital

Sepsis is characterized as a life-threatening organ dysfunction resulting from a dysregulated host response to infection, representing a critical clinical syndrome. Uncontrolled infection and inflammation are two main characteristics of sepsis. Neutrophil extracellular traps (NETs) is a major mechanism by which neutrophils resist pathogens invasion, but the mechanism of the NETs formation remain completely unclear. This study aims to elucidate the role of Histone Deacetylase 2 (HDAC2) in NETs formation and its impact on antimicrobial and anti-inflammatory activities in sepsis. We employed flow cytometry, immunofluorescence and western blotting to assess NETs formation. The effects of HDAC2 on NETs and sepsis outcomes were investigated using an HDAC2 inhibitor and HDAC2 knockout mice in CLP-induced and LPS-induced sepsis models. Histone modifications in neutrophils were also analyzed to explore HDAC2's regulatory mechanism. HDAC2 was found to be highly expressed in patients and mice with sepsis. While HDAC2 knockout or inhibition reduced inflammation and improved organ function in non-infectious sepsis, it decreased survival in infectious sepsis. In addition, knockout or inhibition of HDAC2 significantly reduced the NETs formation, and impaired the antimicrobial activities against E. coli infection in mice. Mechanistically, HDAC2 indirectly promoted H3R17 citrullination to induce the NETs formation through down-regulating H3K18 acetylation and interactively inhibiting CARM1-mediated H3R17 methylation in neutrophils. Furthermore, a dual inhibition strategy targeting HDAC2 and CARM1 not only suppressed inflammation, prevented from multiple organ dysfunction, but also enhanced the antimicrobial activities, which finally improved survival rate of mice with sepsis induced by cecal ligation and puncture (CLP). Our findings reveal a novel role for HDAC2 in modulating anti-infectious immunity through NETs formation during sepsis. This study provides a potential therapeutic strategy for sepsis by enhancing both antimicrobial and anti-inflammatory responses, offering a promising approach to preserve organ function and improve survival.

ObjectiveKeloid, a unique human ailment, poses challenges in scar treatment due to variable efficacy and lengthy therapy and follow-up periods. Therefore, there is a need for a novel approach to address all forms of abnormal scarring. Photodynamic therapy (PDT), although slow-acting, shows promise, particularly when combined with surgery. This study aims to assess the efficacy and potential mechanism of PDT in conjunction with surgery for keloid treatment.MethodsKeloid patients were identified through pathological examination, and the expression of YAP and Engrailed-1 in keloid tissue was determined via immunohistochemistry. Initially, all keloids underwent treatment with 20% ALA-PDT as the initial therapeutic step (the preoperative photodynamic therapy margin extends 0.5 cm beyond the visible lesion edge to ensure full target tissue coverage), using red LED light with specific parameters. Subsequently, keloids were surgically excised 24 hours post-PDT, followed by another PDT session.ResultsImmunohistochemistry assays revealed a significant reduction in YAP and Engrailed-1 levels in keloid tissues post-PDT. Over a minimum 6-month follow-up period, no infections, scar exacerbations, or recurrences were observed, except for postoperative hyperpigmentation.ConclusionThe combination of PDT and surgical therapy demonstrates promising results for keloid treatment. The suppression of YAP leading to reduced Engrailed-1 expression may represent a mechanism underlying the successful treatment of keloids with PDT.

Cancer pain, a complex sensation influenced by psychological and social factors, negatively impacts patients' quality of life and prognosis. Current treatments are often unsatisfactory, partly because key psychosocial factors remain unidentified, creating a barrier to effective care. Further research is needed. This study uses bibliometric analysis and latent Dirichlet allocation (LDA) topic modeling to examine the current research landscape, identify conceptual associations, and uncover unexplored links. A comprehensive literature search on cancer pain and psychosocial factors was conducted in the Web of Science database. Bibliometric visualization analysis was performed on the published studies using Citespace, VOSviewer, the bibliometrix package in R, and KH Coder software. Research on cancer pain and psychosocial factors has shown phased growth, intersecting medicine, biology, psychology, and other fields. Most studies have focused on pain management, quality of life, and psychological impact, with the USA leading global research with 184 publications. Institutions such as Duke University and influential authors such as Breitbart and Bruera have propelled development in this field. The Journal of Pain and Symptom Management-an academic pillar among journals publishing research on cancer pain-is the most cited. Research hotspots have shifted from early "prevalence" and "management" to "quality of life" and "depression." LDA topic modeling identified four major research directions: quality of life and treatment outcomes, pain management and treatment of cancer pain, cancer pain in special populations and contexts, and the multidimensional aspects of cancer pain and its coping strategies. Cancer pain and psychosocial research is a valuable, US-led field with strong international collaboration. The focus has moved from pain management to mental health and quality of life. Future priorities include strengthening multidisciplinary cooperation, exploring molecular mechanisms, and using psychological interventions to achieve personalized, standardized management.