The Second Affiliated Hospital of Xi'An Jiaotong University

Rosacea is a common chronic inflammatory skin disease. Mast cells are implicated in the pathogenesis of rosacea. However, the therapeutic potential of tranilast, a mast cell membrane stabilizer, remains unexplored. This study aims to evaluate the efficacy and safety of tranilast monotherapy and in combination with minocycline in patients with moderate-to-severe rosacea.

This study has been registered on ClinicalTrials.gov (Registration No. NCT06307223). All enrolled patients with rosacea were randomly assigned to receive tranilast, minocycline, or a combination of both. Tranilast (0.1 g, three times daily) and minocycline (50 mg, once daily) were administered for 12 weeks, with follow-up every two weeks.

Forty-five patients completed the study. At week 12, the combination group showed a significantly higher IGA success rate (93.33%) compared to the tranilast (53.33%) and minocycline (46.67%) groups (p < 0.05). The secondary endpoints, such as CEA success rate, erythema index, and erythema score, also favored the combination group over minocycline group (p = 0.021, 0.030, and 0.024, respectively).

In our study, patients with moderate to severe rosacea treated with tranilast showed a favorable clinical response and experienced no serious adverse events. The combination therapy yielded better outcomes than minocycline monotherapy, especially in improving facial erythema.

The World Health Organization has identified ST23 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) as a critical public health threat. Through China's national surveillance system (BRICS), we identified and characterized ST23 CR-hvKP bloodstream isolates from 2019-2023. Among 1069 CRKP bloodstream isolates, four ST23-K1 strains (0.37%) were detected across two hospitals, including a nosocomial transmission pair (differing by only 2 core SNPs). Clinical outcomes revealed that three of the four patients achieved recovery following appropriate antibiotic therapy, with one mortality case attributed to underlying comorbidities. All four ST23 isolates demonstrated resistance to multiple antibiotics, indicating a pattern of multidrug resistance. Genomic analysis uncovered diverse resistance mechanisms: the nosocomial transmission pair possessed conjugative IncFII_K2 NDM-1 plasmids, while the others harbored conjugative IncFII_K34 KPC-2 plasmids, which exhibited reduced carbapenem resistance attributed to the downregulation of bla_KPC-2 expression. Conjugation assays revealed high transferability (10^-5 for IncFII_K2 NDM-1; 10^-4 for IncFII_K34 KPC-2). Whole-plasmid comparative genomics analysis suggested that the IncFII_K2 NDM-1 plasmids shared > 99% identity with historical IncFII_K2 plasmid backbones from Chinese K. pneumoniae isolates (2014-2022), suggesting local evolution. Notably, only 4.4% (26/590) of global IncFII_K2 plasmids carried bla_NDM-1 and all IncFII_K2 NDM-1 plasmids maintain conjugative potential. All strains harbored conserved virulence plasmids and maintained hypervirulence, as indicated by a mouse infection model, with the exception of one strain that exhibited cps mutations. This study reports the first genomic evidence of a high-frequency conjugative IncFII_K2 NDM-1 plasmid in a hospital-transmitted ST23 CR-hvKP clone, highlighting the need for plasmid-focused surveillance to control this potential threat.

Exosomes derived from mesenchymal stem cells (MSCs) have been reported to improve the prognosis in septic mice. Additionally, we have confirmed that TGF-β1 plays a critical role in MSC-mediated protection against sepsis. In this study, we aimed to investigate whether exosomes derived from TGF-β1-overexpressing MSCs (TGF-β1-Exo) offer protective effects in sepsis.

MSCs were collected from mouse MSCs stably transfected with TGF-β1 using a lentiviral vector. Exosomes were isolated and purified from MSCs (Exo), GFP-MSCs (GFP-Exo), and TGF-β1-MSCs (TGF-β1-Exo). A sepsis model was induced in mice via cecal ligation and perforation (CLP). After 6 h, exosomes from different sources were intravenously administered into septic mice. Mice were euthanised 24 h later, and histopathological changes were assessed using hematoxylin and eosin (H&E) staining. Inflammatory cytokine levels were measured using ELISA and RT-PCR. Flow cytometry was employed to evaluate macrophage phenotypes in lung tissues and in vitro macrophages. Additionally, we co-cultured fluorescently labeled exosomes with macrophages in vitro.

TGF-β1-Exo significantly ameliorated histopathological damage and improved survival rates in septic mice. ELISA and RT-PCR analyses revealed that several pro-inflammatory cytokines were notably suppressed in the TGF-β1-Exo group. Furthermore, TGF-β1-Exo promoted the polarization of M1 macrophages to M2 macrophages both in vivo. In vitro, TGF-β1-Exo were internalized by LPS-pretreated macrophages, promoting the shift from the M1 to M2 phenotype, reducing the expression of pro-inflammatory cytokines, and enhancing the production of anti-inflammatory factors.

Our findings suggest that TGF-β1-Exo exert therapeutic effects in septic mice by modulating macrophage polarization and inhibiting macrophage-mediated inflammation.