四川大学学报(医学版)最新文献

Objective: To investigate the protective effects and mechanisms of electroacupuncture on the P2X7 purinergic receptor/NLRP3 signaling pathway in sepsis-associated acute kidney injury (SA-AKI).

Methods: Healthy male C57BL/6J mice, 6-8 weeks old, were randomly assigned to the following groups: control, model, electroacupuncture, P2RX7 antagonist + model, and P2RX7 antagonist + model + electroacupuncture. The SA-AKI model was established by intraperitoneal injection of lipopolysaccharide (LPS). The P2RX7 antagonist A438079 was administered intraperitoneally 1 hour before LPS injection. Electroacupuncture (10 Hz, 0.5 mA, 30 min) was performed 1.5 hours after LPS injection. Mouse survival rates were assessed within 24 hours after modeling. Serum creatinine (Scr) levels were measured by blood biochemistry, IL-1β and IL-18 levels in serum and kidney tissues were measured with ELISA. Renal histopathological changes were observed by HE staining. Real-time fluorescent PCR and immunofluorescence assays were used to assess renal P2RX7 and NLRP3 expression levels.

Results: The 24-hour survival rate in the electroacupuncture group was 45%, a 15% improvement over the model group. Electroacupuncture treatment reduced renal histopathological damage, lowered Scr levels in SA-AKI (P < 0.05), and decreased serum inflammatory mediators IL-1β and IL-18 (both P < 0.0001). Electroacupuncture also reduced renal tissue expression levels of IL-1β (P < 0.0001), IL-18 (P < 0.001), P2RX7, and NLRP3 (both P < 0.05).

Conclusion: The mechanism by which electroacupuncture ameliorates SA-AKI may involve inhibition of the P2RX7/NLRP3 signaling pathway and attenuation of systemic inflammatory responses.

Oral malodor, a common oral symptom, is primarily caused by the metabolic activities of oral microorganisms. The characteristic odors mainly originate from volatile sulfur compounds produced and released by oral bacteria (such as Fusobacterium nucleatum and Porphyromonas gingivalis) through specific enzymatic systems that break down sulfur-containing amino acids in saliva, gingival crevicular fluid, and food debris. Research indicates that various factors, including periodontitis, fungal infections, smoking, and obesity, can worsen oral malodor by altering the oral microenvironment. For prevention and treatment, novel interventions such as plant extracts, antimicrobial peptides, and probiotics demonstrate superior microbiological safety compared to traditional antimicrobial drugs. These approaches specifically inhibit pathogenic bacteria, disrupt biofilm structures, and regulate oral microbial balance. This review summarizes relevant research advances to provide new theoretical foundations and practical directions for the precise prevention and treatment of oral malodor.

Objective: To investigate the characteristics of salivary and supragingival plaque viromes in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), and provide new insights for noninvasive oral screening and ecological intervention for MAFLD.

Methods: This study included 21 MAFLD patients and 20 healthy controls. Saliva and supragingival plaque samples were collected, and metagenomic sequencing was used to analyze the characteristics of the oral virome.

Results: The α-diversity and β-diversity of the salivary virome did not differ significantly between MAFLD patients and healthy individuals (P > 0.05). However, compared with healthy individuals, the α-diversity (Shannon index) and β-diversity (Bray-Curtis distance) of the supragingival plaque virome showed significant differences (P = 0.0303, P = 0.001). For species with a relative abundance greater than 0.1%, 14 viral species in saliva and 5 in supragingival plaque differed significantly in relative abundance between the two groups (P < 0.05), with multiple Streptococcus phages enriched in the saliva of MAFLD patients. LEfSe and random forest analyses identified potential biomarkers in saliva and supragingival plaque. Receiver operating characteristic (ROC) curve analysis showed strong diagnostic performance for these biomarkers in both saliva (area under the curve [AUC] = 0.9548, 95% CI: 0.8898-1.0000) and supragingival plaque (AUC = 0.8952, 95% CI: 0.7774-1.0000). Spearman correlation analysis revealed associations between viral species in saliva or supragingival plaque and various disease indicators (P < 0.05). Compared with healthy individuals, MAFLD patients showed higher node counts, significant relationship numbers, and average node degrees in the co-occurrence networks of salivary and supragingival plaque viromes.

Conclusion: Differences in the species composition and structure of the oral virome between MAFLD patients and healthy individuals suggest that oral viral species could serve as potential biomarkers for diagnosing MAFLD.

Objective: To evaluate the clinical diagnostic value of serological markers, including the 1, 3-β-D-glucan test (G-test), Candida mannan (Mn) antigen, Candida mannan IgG antibody (Mn-IgG), and quantitative real-time PCR(qPCR) in patients with invasive candidiasis (IC).

Methods: This study included 79 patients with culture-proven IC (IC group) and 83 patients without IC (non-IC group) at West China Hospital, Sichuan University between December 2022 and December 2024. Serum samples were tested for the G test (chemiluminescence), Mn antigen (ELISA), Mn-IgG (chemiluminescence), and qPCR. The diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of individual and combined tests were calculated. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis.

Results: The sensitivity, specificity, PPV, and NPV of the three serological markers for IC diagnosis when used individually were as follows: G test, 62.03%, 94.87%, 92.45%, and 71.15%; Mn antigen, 65.63%, 86.59%, 79.25%, and 76.34%; Mn-IgG antibody, 31.65%, 87.95%, 71.43%, and 57.48%. Combined detection of the G test, Mn antigen, and Mn-IgG increased sensitivity to 73.44%. Based on ROC curve analysis, the AUCs for diagnosing IC using each serological marker were: G test, 0.862 (95% CI: 0.803-0.922); Mn test, 0.853 (95% CI: 0.790-0.915); Mn-IgG, 0.603 (95% CI: 0.514-0.692). The combined AUCs for G test + Mn test, G test + Mn-IgG, and G test + Mn test + Mn-IgG were 0.875 (95% CI: 0.809-0.925), 0.869 (95% CI: 0.805-0.917), and 0.875 (95% CI: 0.809-0.924), respectively, demonstrating superiority over individual tests. The sensitivity, specificity, PPV, and NPV of qPCR for IC diagnosis were 100.00%, 98.80%, 98.75%, and 100.00%, respectively. Using culture strain identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as the gold standard, qPCR demonstrated diagnostic concordance rates of 100.00% for Candida albicans, 100.00% for Candida tropicalis, 94.40% for Candida glabrata, and 90.00% for Candida parapsilosis.

Conclusion: The combined use of the G test, Mn antigen, and Mn-IgG antibody increases diagnostic sensitivity and facilitates early diagnosis of IC. qPCR demonstrates excellent diagnostic performance for IC, enabling species-level identification of common Candida species associated with IC and detection of other Candida species. It also shows consistency with clinical culture methods.

mRNA-targeted tumor drugs, featuring various types and distinct antitumor mechanisms of action, have demonstrated significant potential in tumor immunotherapy. Currently, nearly one hundred registered clinical trials initiated by pharmaceutical companies or sponsors are being conducted worldwide, and these trials have shown impressive efficacy. In China, multiple registered clinical trials have been conducted in the past two years, reflecting rapid development. Although mRNA tumor drugs still face certain challenges, the advantages of mRNA technology are clear, promoting the integrated development of immunotherapy, gene therapy, and cell therapy. With ongoing technological innovation and optimization, the demand for "mRNA therapy" for tumor prevention and treatment is expected to be met. This review discusses the distinct mechanisms of action, progress in basic research, clinical advancements, challenges, and future perspectives of both prophylactic and therapeutic mRNA cancer vaccines. It aims to enhance understanding of research progress in mRNA technology for oncological drug applications and to provide insights for future research and product development of mRNA-based interventions in oncology.

Objective: To investigate the in vitro inhibitory and bactericidal activities of the trans-2-decenal compound against Helicobacter pylori (H. pylori) and explore its potential mechanism.

Methods: The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of trans-2-decenal against H. pylori clinical isolates and the standard strain ATCC43504 were determined using the broth microdilution method. Changes in MIC values were monitored to assess drug resistance in H. pylori induced by continuous treatment with trans-2-decenal. The synergistic antibacterial effect of combining trans-2-decenal with antibiotics such as metronidazole (MTZ), clarithromycin (CLA), amoxicillin (AMX), and levofloxacin (LEV) was evaluated using the fractional inhibitory concentration index (FICI). After treating standard H. pylori strains with trans-2-decenal, scanning electron microscopy, transmission electron microscopy, crystal violet staining, the semi-solid puncture method, and the Berthelot method were used to assess the effects of trans-2-decenal on the morphology, cell structure, migration, and urease activity of H. pylori.

Results: The MIC range for clinically resistant H. pylori strains C907, C101, R1, R2, R4, R10, R16, R24, R36, and R40 was 8-16 μg/mL, with an MBC range of 16-32 μg/mL. The MIC for the H. pylori standard strain ATCC43504 was 16 μg/mL, with an MBC of 16 μg/mL.Trans-2-decenal inhibits H. pylori at low concentrations for short durations and does not easily induce H. pylori resistance. Trans-2-decenal reduces the required dosage of antibiotics (metronidazole and levofloxacin), showing an additive effect. Trans-2-decenal alters the shape of H. pylori and promotes bacterial rupture. Furthermore, Trans-2-decenal exerts its effects by altering H. pylori morphology, inducing bacterial rupture, inhibiting biofilm formation, reducing the number of mature biofilms, and decreasing urease activity and H. pylori migration ability.

Conclusion: Trans-2-decenal may inhibit H. pylori in vitro through multiple mechanisms and is unlikely to promote the development of H. pylori resistance.

Periodontitis and metabolic dysfunction-associated fatty liver disease (MAFLD) are both highly prevalent chronic diseases that impose a significant global burden. Recent studies have revealed a close association between them. This article systematically reviews the epidemiological link between periodontitis and MAFLD, as well as their potential underlying mechanisms. Regarding the investigation of underlying mechanisms, the article focuses on two primary pathways. Firstly, the classical hematogenous transmission pathway, in which periodontal pathogens and their mediated inflammatory responses affect the liver through the systemic circulation; secondly, the recently proposed "oral-gut-liver axis" pathway, in which periodontitis alters the oral microbiota, subsequently disrupting gut microbiota and intestinal barrier function, ultimately leading to hepatic metabolic dysregulation. These studies offer new perspectives for understanding the complex relationship between these diseases and provide potential novel strategies for the prevention and treatment of MAFLD.

Protein phosphorylation is a key mechanism regulating cell wall synthesis in Streptococcus. Serine/threonine kinases (STKs) and the two-component system dynamically regulate peptidoglycan synthesis and assembly through phosphorylation, profoundly influencing bacterial shape maintenance, division, and drug resistance. Studies indicate that serine/threonine kinases form a core network regulating cell wall stability by phosphorylating key scaffold proteins such as DivIVA and GpsB, making them important potential targets for novel antimicrobial agents. Despite significant research progress, the spatiotemporal dynamics of this phosphorylation network and its interactions with other modification systems, such as acetylation and ubiquitination, remain to be thoroughly elucidated. Future research should integrate frontier technologies such as high-throughput proteomics and AI-based structural prediction to comprehensively elucidate this complex regulatory system, thereby providing novel strategies to address antimicrobial resistance challenges.