四川大学学报(医学版)最新文献

Objectives: To summarize and analyze the clinical manifestations of acute pancreatitis associated with childhood systemic lupus erythematosus (cSLE) and to evaluate the therapeutic efficacy of plasma exchange combined with glucocorticoids.

Methods: This retrospective study analyzed clinical data from cSLE patients diagnosed and treated at West China Second University Hospital from January 2018 to December 2020. Patients were divided into a pancreatitis group (diagnosed with cSLE-associated acute pancreatitis) and a non-pancreatitis group (without this diagnosis), and differences between groups were compared.

Results: Among 170 cSLE patients enrolled, 9 were in the pancreatitis group and 161 were in the non-pancreatitis group. The median SLEDAI score was 24.0 (P25-P75: 20.5-29.0) in the pancreatitis group and 18.0 (P25-P75: 14.0-20.0) in the non-pancreatitis group, with a statistically significant difference (P < 0.05). The incidence rates of abdominal pain, vomiting, abdominal distension, diarrhea, acute pericarditis, and macrophage activation syndrome were higher in the pancreatitis group than in the non-pancreatitis group, with statistically significant differences (P < 0.05). Differences in C-reactive protein, hemoglobin, blood urea nitrogen, serum albumin, serum amylase, serum lipase, and lipid levels between the two groups were also statistically significant (P < 0.05). Multivariate logistic regression analysis indicated that each 1-point increase in SLEDAI score was associated with a 37.5% higher risk of developing pancreatitis (OR 1.375, 95% CI 1.121-1.686, P =0.002). All children in the pancreatitis group received high-dose glucocorticoids combined with multiple plasma exchanges, followed by immunosuppressive therapy. Nine patients achieved remission from acute pancreatitis within two weeks of treatment. Two patients died within 30 days, but the cause of death was unrelated to acute pancreatitis.

Conclusion: Acute pancreatitis is a rare but severe complication of cSLE, with higher SLEDAI scores correlating with increased risk of pancreatitis. Early diagnosis and aggressive treatment with glucocorticoids combined with plasma exchange may be associated with improved short-term outcomes.

Objective: To investigate the association between serum sodium and potassium levels and the risk of depressive symptoms during the second trimester of pregnancy.

Methods: This study was based on a prospective birth cohort of pregnant women who registered at Chongqing Maternal and Child Health Hospital, China, between 2018 and 2020. Depressive symptoms were assessed during the second trimester using the Edinburgh Postnatal Depression Scale (EPDS). Serum sodium and potassium levels were extracted from electronic health records. Logistic regression models were used to analyze the association between serum sodium and potassium levels and the risk of depressive symptoms.

Results: Among the 1429 participants, the prevalence of depressive symptoms was 52.76%. A significant negative association was observed for serum potassium, while no significant association was found between serum sodium levels and the risk of depressive symptoms. In the fully adjusted model, the highest quartile (Q4) of serum potassium was associated with a lower risk of depressive symptoms compared to the lowest quartile (Q1) (odds ratio [OR] = 0.715, 95% CI: 0.531 to 0.963).

Conclusion: Within the normal physiological range, serum potassium levels were associated with the risk of depressive symptoms during the second trimester of pregnancy, whereas no significant association was found for serum sodium levels.

Objective: To investigate how neutrophil-derived microvesicles (NDMV) promote LINE1 gene hypermethylation in fibroblast-like synoviocytes (FLS) by regulating DNA methyltransferases (DNMT).

Methods: Neutrophils were isolated from the peripheral blood of healthy volunteers and stimulated with tumor necrosis factor α (TNFα) to produce NDMV. Primary FLS were cultured to the fourth passage for use. MTT assays determined the optimal NDMV treatment ratios and durations for FLS. Experiments groups included control, TNFα, NDMV, and TNFα + NDMV. Combined bisulfite restriction analysis (COBRA) assessed global LINE1 methylation levels and methylation at two specific sites. RT-qPCR and Western blot analyzed phosphorylated and non-phosphorylated DNA methyltransferase 1 (DNMT1) expression in each group.

Results: No significant cytotoxicity was observed at NDMV∶FLS ratios ≤ 100∶1 (P > 0.05). NDMV treatment for 24 hours had no significant effect on FLS cell viability (P > 0.05). The overall methylation level of the LINE1 gene in the TNFα group was (37.62 ± 2.38)%, which differed significantly from the control group (58.97 ± 1.50)%, NDMV group (59.59 ± 1.15)%, and TNFα + NDMV group (59.11 ± 0.85)%, P < 0.001. Compared with the TNFα group, methylation levels at LINE1 sites 1 and 2 in the control, NDMV, and TNFα + NDMV groups also showed statistically significant differences (P < 0.01). The relative expression levels of phosphorylated DNMT1 protein in the control group, TNFα group, NDMV group, and TNFα + NDMV group were 1.00 ± 0.01, 0.40 ± 0.01, 2.18 ± 0.02, and 1.58 ± 0.05, respectively (P < 0.001).

Conclusion: NDMV enhances LINE1 gene methylation by regulating phosphorylated DNMT1 expression in FLS.

The oral cavity is a complex microecosystem that provides a suitable habitat for diverse microorganisms, including bacteria, archaea, fungi, viruses, and protozoa. The microbial communities in the oral cavity form a stable microecology through complex interactions and environmental adaptation. In a healthy oral microenvironment, various microorganisms maintain microecological balance through signal communication, material exchange, competition and cooperation for resources and environmental conditions, quorum sensing, and environmental adaptation. In contrast, an imbalanced oral microecology can lead to oral diseases such as endodontic and periodontal diseases, and may even affect systemic health. Natural products have attracted significant attention for maintaining oral microecological balance due to their potential antibacterial, anti-inflammatory, biofilm-inhibiting, and microecology-regulating properties. This article systematically reviews the characteristics of natural products, their mechanisms for regulating oral microecological balance, and their application prospects and limitations in oral disease prevention and treatment, providing a reference for the use of natural products in maintaining oral microecological balance.

Objective: To investigate the mechanism by which chlorhexidine and Polident, commonly used denture cleansers, induce the formation of persistence in Candida albicans (C.a.), which is the causative agent of denture stomatitis.

Methods: C.a. biofilms were formed and treated with 0-40000 μg/mL chlorhexidine and Polident. Surviving colonies were counted, and dose- and time-dependent curves were plotted. The distribution of persisters was observed via vital staining, and retention was verified by isolating surviving colonies. Transcriptomic analysis was performed on strains treated with chlorhexidine for 2 and 6 hours to explore the mechanisms of persister formation. Metabolic changes in persisters were assessed using the MTT assay. Exogenous glucose was added to validate the role of denture cleansers in regulating persister metabolism.

Results: After treating C.a. biofilms with chlorhexidine and Polident, the dose- and time-response curves of viable cells both exhibited a biphasic bactericidal pattern, indicating the formation of C.a. persisters. The biofilm structure was disrupted, and persisters were mostly distributed in the middle and upper layers. Transcriptomic analysis showed marked downregulation of the TCA cycle and aerobic respiration, but upregulation of glycolysis. The MTT assay verified that chlorhexidine and Polident suppressed persister metabolism, while the addition of glucose reduced the persister populations; there was a statistically significant difference compared to the control group (P < 0.05).

Conclusion: High concentrations of chlorhexidine and Polident can induce the formation of C.a. persisters, which are mainly distributed in the upper and middle layers of biofilms. The persisters can resuscitate after drug removal, increasing the risk of recurrent infections. C.a. shifts from the tricarboxylic acid cycle and aerobic respiration to glycolysis to maintain a low metabolic level. Exogenous glucose can activate their metabolism and decrease the number of persisters.

This article systematically reviews the associations and mechanisms between the oral microbiome and inflammatory bowel disease (IBD). Relevant literature was retrieved from the PubMed database from January 2000 to October 2025, and 77 articles meeting the criteria for inductive analysis were selected. The results confirm a bidirectional causal relationship between oral dysbiosis and IBD: patients with IBD exhibit reduced oral microbial diversity, increased abundance of pathogenic bacteria (such as Fusobacterium nucleatum and Porphyromonas gingivalis), and a more active oral immune environment. Oral pathogens can migrate to the gut via the oral-gut axis, directly disrupting the intestinal barrier and microbial homeostasis or activating systemic and intestinal immune responses through pathways such as miRNAs carried by exosomes and immune cell migration, thereby exacerbating IBD. However, current studies have several limitations, including small sample sizes, high heterogeneity in conclusions, lack of longitudinal data, and insufficient technical compatibility. Future research should expand investigations into the roles of oral fungi and viruses and integrate multiomics technologies to advance the clinical translation of oral microbiota in IBD diagnosis and treatment.

Objective: To analyze the oral and gut microbial composition in preschool children during the deciduous and mixed dentition stages, and to investigate the characteristics of microbiota across different dentition stages.

Methods: Using 16S rRNA gene-based third-generation sequencing, this study analyzed saliva and fecal samples collected from 10 children with deciduous dentition and 10 with mixed dentition. The composition and differences in oral and gut microbiota between the two groups were compared.

Results: The differences in microbial richness (Chao1 index) and evenness (Shannon index) between the oral cavity and intestine were statistically significant (P = 0.001). Firmicutes, Proteobacteria, and Bacteroidetes were the three dominant phyla at both sites. At the genus level, Neisseria and Streptococcus were abundant in the oral cavity, while Bacteroides and Faecalibacterium predominated in the gut. o_Lactobacillus (LDA = 5.04, P < 0.001) was identified as a marker genus in the oral cavity during the deciduous dentition period, while g_Neisseria (LDA = 5.15, P < 0.001) served as an oral marker genus in children with mixed dentition. In the gut, marker genera during the deciduous dentition period included o_Bacteroides (LDA = 5.17, P < 0.001) and f_Lachnospiraceae (LDA = 5.16, P < 0.001), whereas f_Ruminococcus (LDA = 5.09, P < 0.001) and g_Faecalibacterium (LDA = 5.03, P < 0.001) were marker genera during the mixed dentition period. Upregulation of pathways including lactose degradation and nitrate reduction was observed in the oral microbiota, in contrast to the gut microbiota, where enhanced activity of the methanogenesis from acetate pathway was noted.

Conclusion: The composition of oral and gut microbiota varies among children at different dentition stages. As dentition changes, the structural diversity and metabolic functions of both oral and gut microbiota also change.

Objective: To investigate the relationship between very long chain saturated fatty acids (VLCSFAs) levels in the serum of American adults and chronic kidney disease (CKD), thereby providing new insights for the prevention and treatment of CKD.

Methods: Using data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES), individuals under 20 years of age and those lacking serum creatinine, blood urea nitrogen, urine albumin-to-creatinine ratio (uACR), or other covariate data were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI (2009) equation. The independent relationship between VLCSFAs and CKD was examined using weighted multivariate logistic regression, the XGBoost machine learning model, and subgroup analyses. Restricted cubic splines (RCS) were used to test for nonlinear associations.

Results: A total of 4164 participants were analyzed. Serum VLCSFAs levels differed significantly between the CKD and non-CKD groups (P < 0.05). In fully adjusted models, weighted multivariate logistic regression revealed a decreasing trend in CKD risk with increasing serum VLCSFAs levels, particularly for docosanoic acid, tricosanoic acid, and lignoceric acid, which significantly reduced CKD risk (docosanoic acid: odds ratio [OR] = 0.17, 95% CI: 0.06-0.43, P < 0.001; tricosanoic acid: OR = 0.02, 95% CI: 0.002-0.15, P < 0.001; lignoceric acid: OR = 0.13, 95% CI: 0.04-0.40, P < 0.001). RCS analysis showed no nonlinear association between VLCSFAs and CKD. The XGBoost machine learning model identified triacontanoic acid as the most important factor for CKD risk. Subgroup analysis indicated that docosanoic acid, tricosanoic acid, and lignoceric acid exerted protective effects only in CKD participants with concomitant hypertension, while showing no impact on those with diabetes, coronary heart disease, or stroke.

Conclusion: Elevated circulating VLCSFAs levels in US adults are associated with reduced CKD risk. Further large-scale prospective studies are needed to validate these findings.

Objective: To investigate the risk factors for secondary pulmonary infarction (PI) in elderly patients with acute pulmonary embolism (PE) and to construct a risk prediction model based on these factors.

Methods: This study enrolled 147 elderly PE patients hospitalized at our institution from July 2018 to September 2022. Patients were divided into a secondary PI group (n = 44) and a non-secondary PI group (n = 103) based on the occurrence of secondary PI. Stepwise regression analysis was used to identify risk factors for secondary PI, and a risk prediction model was constructed using R software. The model was validated with 63 elderly PE patients admitted between September 2022 and December 2023. Results Stepwise regression analysis identified alcohol consumption (odds ratio [OR] = 8.586, 95% CI: 2.430-30.361), chronic bronchitis (OR = 9.831, 95% CI: 2.701-35.782), emphysema (OR = 6.990, 95% CI: 1.987-24.582), coronary heart disease (OR = 15.603, 95% CI: 3.470-41.144), diabetes (OR = 11.955, 95% CI: 1.097-130.860), and D-dimer (OR = 1.021, 95% CI: 1.002-1.037) as independent risk factors for secondary PI in elderly PE patients (P < 0.05). Receiver operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.936 (95% CI: 0.901-0.976) for the modeling group and 0.917 (95% CI: 0.852-0.990) for the validation group. Calibration curve results indicated that the model demonstrated high accuracy in both the modeling and validation cohorts. Clinical decision curve analysis showed the model has high clinical utility.

Conclusion: Elderly PE patients with alcohol consumption, chronic bronchitis, coronary heart disease, emphysema, diabetes, or elevated D-dimer levels have a higher risk of secondary PI. The predictive model demonstrates high discriminatory power and accuracy, aiding clinical assessment of secondary PI in PE patients.

Objective: To analyze the differential expression of nucleotide-binding oligomerization domain 1 (NOD1) in maternal-fetal interface cells during early and late pregnancy, and to investigate its molecular mechanisms in mediating inflammatory responses.

Methods: Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect NOD1 mRNA and protein expression in normal first-trimester villi tissues (n = 30), normal early pregnancy decidua tissues (n = 30), and normal full-term placental tissues (n = 30). Human chorionic trophoblast HTR8/SVneo cells were stimulated with tumor necrosis factor-alpha (TNFα) at various concentrations (0, 0.01, 0.1, 1, 10, and 100 ng/mL) and exposure times (24, 48, and 72 h). Real-time quantitative PCR (qRT-PCR) and western blot analysis were performed to detect differential expression of NOD1, receptor-interacting protein (RIP)-like interacting CLARP kinase (RICK), and p65. ELISA was used to analyze the secretion levels of inflammatory cytokines IL-6 and IL-8. Electrophoretic mobility shift assay (EMSA) was conducted to assess the DNA-binding activity of nuclear factor-kappa B (NF-κB) and to investigate the regulatory mechanisms of NOD1 signaling pathways in trophoblasts.

Results: NOD1 was expressed in normal first-trimester villi, decidua, and full-term placental tissues, primarily localized in the cytoplasm of trophoblasts, vascular endothelial cells, and decidual cells. The difference in NOD1 expression between full-term placental tissues and first-trimester villi and decidua was statistically significant (P < 0.05), with higher NOD1 expression observed in full-term placental tissues than in first-trimester villi and decidua. TNFα upregulated NOD1 expression in HTR8/SVneo cells in a dose- and time-dependent manner. IL-6 secretion levels positively correlated with TNFα concentration, while IL-6 and IL-8 release exhibited time-dependent responses to TNFα stimulation. Furthermore, TNFα stimulation enhanced RICK and p65 expression and increased NF-κB DNA-binding activity.

Conclusion: NOD1 is constitutively expressed in trophoblasts and decidual cells at the maternal-fetal interface during normal pregnancy, participating in the regulation of the gestational process. Changes in NOD1 expression correlate with TNFα-induced inflammatory responses. TNFα may trigger inflammatory cytokine release via the NOD1-RICK-NF-κB signaling axis, mediating inflammatory cascades in trophoblasts. These findings provide novel insights into immune regulatory mechanisms during pregnancy.