Open Medicine最新文献

Objectives: To investigate the surgical outcomes of coronal shear fractures of the capitellum and trochlea (CSFCT) guided by the Dubberley classification.

Methods: A retrospective analysis was conducted on patients with CSFCT between January 2015 and December 2023. Demographic information, surgical details, functional recovery outcomes, and postoperative complications were recorded and compared across fracture subgroup.

Results: 39 patients were included (mean age: 44.3 ± 15.5 years) with a mean follow-up of 38.2 ± 12.0 months. All patients underwent surgery via an extended lateral approach using various hardware. Postoperatively, the mean extension deficit was - 0.9°, mean flexion was 126.4°, and mean flexion-extension arc was 125.4°. The mean Mayo Elbow Performance Scores (MEPS) was 87.9 (66.7 % excellent, 30.8 % good, 2.5 % fair). Dubberley type 2 and A fractures had higher MEPS than type 3 and B, respectively (both p<0.01). Postoperative complications included two elbow stiffness, two implant prominence, and one avascular necrosis case.

Conclusions: Under the guidance of the Dubberley classification, surgical treatment for patients with CSFCT has achieved greater efficacy, favorable outcomes, and low complication rates.

Objectives: To determine the safety and effectiveness of the anticoagulation regimen nafamostat mesylate for continuous renal replacement therapy in patients with sepsis-associated AKI.

Methods: According to the inclusion and exclusion criteria, a total of 42 patients with sepsis and complicated renal function impairment who required CRRT were included. Among them, 2 patients were excluded because their admission time was less than 24 h. Finally, 40 patients were included. The Nafamostat mesylate anticoagulation method was selected for the experimental group and regional citrate anticoagulation was used in the control group.

Results: At admission (experimental group vs. control group), the following findings were obtained: sCr: 391.2 ± 1.94 vs. 389.7 ± 1.46 ummol/L, BUN: 12.97 ± 1.51 vs. 11.86 ± 1.75 mmol/L, APTT: 23.43 ± 1.27 vs. 24.12 ± 1.53 s, and Plt: 80.15 ± 12.27 vs. 83.15 ± 10.35 × 109/L. Four hours after CRRT treatment, the following findings were obtained: sCr: 280.85 ± 1.89 vs. 283.41 ± 1.46 ummol/L, BUN: 12.02 ± 1.55 vs. 11.86 ± 1.75 mmol/L, APTT of prefilter: 41 ± 3.89 vs. 25.31 ± 2.17 s, postfilter: 81.63 ± 3.76 s, Plt: 80.2 ± 13.04 vs. 83.15 ± 10.35 × 109/L, and pH 7.37 ± 0.03 vs. 7.41 ± 0.02. A comparison of sCr and APTT (prefilter) revealed that p<0.05 was statistically significant, but there was no significant difference in the other indicators. In the control group, citrate accumulation occurred in 2 patients; for a total calcium/arterial calcium ion concentration >2.5, there were no obvious adverse reactions. The lifespans of the first filter were 60.2 ± 10.09 and 59.07 ± 11.44 h, and the ICU lengths were 7.35 ± 1.35 and 7.21 ± 1.17 days, Nafamostat mesylate prolonged filter lifespan compared to RCA, however, ICU LOS was same.

Conclusions: The anticoagulation regimen of nafamostat mesylate may be safe and effective in patients with sepsis-associated AKI receiving CRRT.

Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major clinical and public health threat due to its high mortality in sepsis and the complexity of its resistance mechanisms, which greatly limit therapeutic effectiveness. Outer membrane vesicles (OMVs) secreted by Gram-negative bacteria harbor various virulence factors and resistance determinants, and may facilitate long-distance pathogenic communication. However, the OMV protein composition of CRKP isolated from sepsis patients remains poorly understood. This study aimed to characterize the protein cargo of OMVs derived from clinical CRKP isolates and to identify differential proteins and pathways associated with bacterial pathogenicity and carbapenem resistance.

Methods: Three CRKP and three carbapenem-sensitive K. pneumoniae (CSKP) were isolated from blood cultures of patients with sepsis, and then their OMVs were extracted. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and SDS-PAGE were used for characterization. Quantitative proteomic profiling was performed using LC-MS/MS, followed by differential expression analysis, Gene Ontology (GO), KEGG pathway enrichment, and protein-protein interaction (PPI) network analysis.

Results: A total of 1,193 OMV proteins were identified, with CRKP-OMVs containing substantially more unique proteins (140 vs. 5 in CSKP-OMVs) and significantly increased overall protein abundance. Among the 199 differential proteins, 180 were upregulated in CRKP-OMVs. Most differential proteins were localized to the membrane or cytoplasm, and were enriched in enzymatic functions and pathways including β-alanine metabolism, O-antigen nucleotide sugar biosynthesis, Lipopolysaccharide biosynthesis, and β-lactam resistance. Key proteins such as adhE, NDK, treA, and ackA were markedly elevated, while galE and Ter family proteins were uniquely present in CRKP-OMVs, indicating potential roles in resistance and pathogenicity.

Conclusions: CRKP-derived OMVs from sepsis patients exhibit distinct protein enrichment patterns associated with membrane functions, metabolic remodeling, and antibiotic resistance. These findings provide insights into CRKP pathogenesis and highlight candidate OMV-associated proteins that may serve as targets for antimicrobial strategies or vaccine development.

Objective: Gasdermin D (GSDMD), a key pyroptosis effector, is implicated in systemic inflammation during sepsis. However, its role in skeletal muscle metabolism remains largely unexplored.

Methods: GSDMD-knockout (GSDMD-KO) and wild-type (WT) mice were used to establish a septic model. Skeletal muscle samples were collected and subjected to non-targeted metabolomic analysis via UHPLC-QE-MS. Multivariate statistical analysis and KEGG pathway enrichment were performed to identify differential metabolites and explore the underlying metabolic alterations.

Results: GSDMD knockout resulted in significant changes in skeletal muscle metabolism, notably in pathways related to taurine and hypotaurine metabolism, amino acid biosynthesis, bile acid biosynthesis, oxidative stress response, and nucleotide metabolism. These alterations suggest that GSDMD regulates energy, amino acid, lipid, and redox metabolism during sepsis. A panel of potential biomarkers was identified, which may contribute to muscle injury and repair.

Conclusions: GSDMD deficiency profoundly alters skeletal muscle metabolic profiles in sepsis. Identified metabolites may serve as diagnostic markers and therapeutic targets for sepsis-associated myopathy, offering insights into GSDMD's role in muscle metabolism and potential intervention strategies.

Objectives: This study aimed to investigate the expression of programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) on CD4⁺ and CD8⁺ T cells in children with asthma and their relationship with Th2-associated inflammatory cytokines (IL-4, IL-5, and IL-13). The goal was to elucidate the potential roles of these immune checkpoint molecules in asthma pathogenesis and severity.

Methods: A prospective observational study was conducted involving 112 asthmatic children aged 5-15 years and 100 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to analyze the frequencies of PD-1⁺ and LAG-3⁺ T cells. Serum levels of IL-4, IL-5, and IL-13 were measured using ELISA. Asthma severity was classified according to the Global Initiative for Asthma (GINA) guidelines, and demographic, clinical, and lung function data were collected. Statistical analyses included Pearson correlation, ROC curve analysis, and logistic regression to assess the diagnostic and prognostic value of PD-1 and LAG-3 expression.

Results: Asthmatic children, particularly those with moderate-to-severe disease, exhibited significantly higher frequencies of PD-1⁺ and LAG-3⁺ T cells compared to healthy controls. Serum levels of IL-4, IL-5, and IL-13 were also elevated in asthmatic children, with the highest levels observed in moderate-to-severe cases. The frequencies of PD-1⁺LAG-3⁺ T cells were positively correlated with IL-13 levels and negatively correlated with lung function parameters, including FVC%, FEV1%, and PEF%. ROC curve analysis demonstrated that CD4⁺PD-1⁺LAG-3⁺ T cells had superior diagnostic performance for moderate-to-severe asthma. Logistic regression identified CD4⁺LAG-3⁺PD-1⁺, and IL-13 as independent risk factors for moderate-to-severe asthma.

Conclusions: The elevated frequencies of PD-1 and LAG-3 on T cells in asthmatic children, particularly in those with moderate-to-severe disease, suggested that these immune checkpoint molecules play a critical role in asthma pathogenesis and severity. These findings highlighted the potential of PD-1 and LAG-3 as biomarkers for asthma severity and therapeutic targets, offering new avenues for immune modulation in pediatric asthma management.

Objectives: To investigate the effects of swimming on bone loss and the OPG/RANKL/RANK pathway in ovariectomized (OVX) osteoporotic rats.

Methods: Twenty female SD rats were randomly divided into a sham-operated group, a ovariectomized osteoporosis group, a short-duration exercise group, and a long-duration exercise group. Bone volume fraction (BV/TV), trabecular thickness (Tb.Th), bone mineral density (BMD), trabecular separation (Tb.Sp), and trabecular number (Tb.N) of bone tissue were measured by Micro-CT. The expression of human C-terminal peptide collagen type I (CTX-Ⅰ), tartrate-resistant acid phosphatase 5b (TRAP-5b), bone-specific alkaline phosphatase (BALP) and serum bone glycoprotein (BGP) were measured by ELISA. The mRNA and protein expression of OPG, RANKL, and RANK in bone tissue were detected by qRT-PCR and Western bolt, respectively.

Results: After swimming treatment, compared with the ovariectomized osteoporosis group, BV/TV, BMD, Tb.Th, and Tb.N increased, while Tb.Sp decreased; CTX-Ⅰ, TRAP-5b, BGP, and BALP levels decreased. OPG mRNA and protein expression increased, while RANKL and RANK decreased.

Conclusions: Swimming training alleviated ovariectomy-induced bone loss and was accompanied by a shift of the OPG/RANKL/RANK axis toward an anti-resorptive profile, suggesting that modulation of this pathway may contribute to the bone-protective effects of swimming. Further functional studies are warranted to test causality.

Objectives: Serum lactate and albumin levels upon admission are independent risk factors for poor prognosis in patients with cardiogenic shock (CS). The association between the serum lactate/albumin ratio (LAR) and mortality in patients with cardiogenic shock remains unclear. This study aims to explore the relationship between LAR at admission and the 90-day mortality of patients with CS.

Methods: We performed a secondary analysis of previously published data on cardiogenic shock patients. Based on the curve, an LAR of >0.094 indicated a harmful threshold. The outcomes of cardiogenic shock Patients dichotomized according to the LAR cut-off value. Univariate logistic regression models, the receiver operating characteristic (ROC) curve in the multivariate analysis, a restricted cubic spline plot derived from multivariate logistic regression, Decision curve analysis and subgroup analyses were employed to investigate the association between LAR and mortality of cardiogenic shock.

Results: A total of 176 patients were included. Univariate logistic analyses revealed a positive association between LAR and 90-day mortality of cardiogenic shock patients (HR 4.50, 95 % CI=2.64-7.66, p<0.001). The Area Under the Curve (AUC) value for LAR was 0.781 (95 % CI: 0.713-0.848), which was higher than that for initial lactate (AUC=0.768) and albumin (AUC=0.652) alone. It was not inferior even when compared to IABP-SHOCK II score (AUC=0.719). The restricted cubic spline analysis demonstrated a linear relationship between baseline LAR and the mortality of patients with cardiogenic shock. The Kaplan-Meier curves indicate lower survival rates in patients with LAR values >0.094. Decision curve analysis shows that LAR model has the best utility in intermediate-risk clinical decisions (30-75 % threshold). The final subgroup analysis showed no significant interaction of LAR with each subgroup (P for interaction: 0.057-0.948).

Conclusions: The baseline Lactic/albumin Ratio (LAR) in patients experiencing cardiogenic shock shows a positive correlation with mortality associated with this condition. The findings indicate a significant increase in the mortality rate when the LAR exceeds a certain threshold. Furthermore, the LAR serves as an independent risk factor for poor prognosis in patients suffering from cardiogenic shock, with superior prognostic performance than initial lactate or serum albumin alone. Clinicians use LAR for personalized risk assessment when they encounter a medium probability scenario for 90-day mortality.

Objectives: This study aimed to explore the mechanism by which exogenous macrophage migration inhibitory factor (MIF) reduces apoptosis of mouse bone marrow mesenchymal stem cells (BMSCs) induced by irradiation under high oxidative stress.

Methods: BMSCs were cultured and exposed to irradiation using a linear accelerator to establish a radiation damage model. Cell viability was detected by the CCK-8 assay. Apoptosis rate and intracellular reactive oxygen species (ROS) production were measured by flow cytometry and fluorescence microscopy. The expression levels of Long non-coding RNA (lncRNA) MEG3, NOX4, and apoptosis-related genes were detected by western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence.

Results: The CCK-8 assay, western blot, and flow cytometry confirmed that irradiation effectively induced BMSCs apoptosis and upregulated the expression of lncRNA MEG3, which was positively correlated with NOX4 expression. Western blot, immunofluorescence, and RT-qPCR results demonstrated that MIF protected BMSCs from irradiation-induced apoptosis and downregulated the expression of MEG3 and NOX4. Furthermore, MEG3 siRNA was shown to reduce irradiation-induced apoptosis. Western blot and flow cytometry analyses revealed that overexpression of either NOX4 or MEG3 could reverse the protective effect of MIF.

Conclusions: LncRNA MEG3 is an important regulatory factor in irradiation-induced apoptosis. The mechanism by which MIF protects BMSCs from irradiation-induced apoptosis is likely mediated through the regulation of the LncRNA MEG3/NOX4 signaling pathway.

Objectives: The research on idiopathic recurrent pregnancy loss (RPL) mainly focuses on women, but recently researchers began to explore the potential contribution of male partners. Growing evidence suggests that male tuberculosis may contribute to adverse pregnancy outcomes. We studied whether men's previous tuberculosis may contribute to idiopathic RPL in early pregnancy.

Methods: A retrospective study on 182 couples with idiopathic RPL in early pregnancy (study group) and 260 couples with fertility (control group) who visited the Fourth Hospital of Hebei Medical University from January 1, 2021 to December 31, 2022 was conducted. Logistic regression analysis was performed to nvestigate the correlation between male partner's previous pulmonary tuberculosis and idiopathic RPL.

Results: Male partners accounted for 37.91 % of previous pulmonary tuberculosis in the study group, and the sperm DNA fragmentation index (DFI) in the study group was higher than that in the control group (17.52 ± 7.87 vs. 7.79 ± 4.49, p=0.000). After adjusting for factors, Logistic regression analysis showed that male partners with previous tuberculosis history were prone to RPL (p=0.000), and male partners with untreated tuberculosis history were more prone to idiopathic PRL [treated tuberculosis history vs. untreated tuberculosis (OR 29.557, 95 % CI 6.437-135.708, p=0.000), no tuberculosis history vs. untreated tuberculosis history (OR 73.856, 95 % CI 13.139-415.150, p=0.000)]. Spearman correlation showed that the prevalence of tuberculosis in male partners was positively correlated with DFI (R=0.492, p=0.000) and negatively correlated with testosterone (R=-0.120, p=0.012).

Conclusions: Among the couples with idiopathic PRL, male partners with a history of pulmonary tuberculosis (especially untreated pulmonary tuberculosis) are more prone to PRL, which maybe caused by high DFI and low testosterone.

Objectives: Patients with long-term ulcerative colitis (UC) have a significantly increased risk of colon cancer compared to normal individuals. By analyzing the pathways of ulcerative colitis and colon cancer, we identified a common risk pathway - Vascular Endothelial Growth Factor (VEGF).

Methods: Based on the Gene Set Variation Analysis (GSVA) scores of the VEGF pathway in colon cancer patients, we divided them into three groups: high, medium, and low. We performed clinical characteristic and immune-related analyses on these three groups, conducted differential gene analysis, performed univariate and multivariate Cox analyses on the differential genes to screen out gene signatures. A risk model was constructed and validated in the UC cohort. Colon cancer patients were classified into high-and low-risk groups based on risk scores, clinical characteristics, immune microenvironment, immunotherapy, and drug sensitivity were analyzed for both groups.

Results: The high expression group had higher clinical staging and pathologic staging, higher immune microenvironment scores, and greater immune cell content. The risk model we constructed demonstrated good prognostic predictive ability not only for colon cancer but also for UC. The high-risk group had a lower survival rate, while the low-risk group had a better response to immunotherapy.

Conclusions: These findings provide new insights into the treatment of colon cancer.