Archives of Medical Science最新文献

Introduction: Osteoarthritis of the hip or knee has been reported to be linked to an increased risk of frailty. However, a definitive conclusion about whether hip or knee osteoarthritis increases susceptibility to frailty remains elusive.

Material and methods: The instrumental variables (IVs) used in this analysis were sourced from publicly available genome-wide association study (GWAS) datasets. We used a two-sample Mendelian randomization analysis to evaluate the plausible causal nexus between hip or knee osteoarthritis and frailty.

Results: We included a total of 25 single-nucleotide polymorphisms (SNPs) as instrumental variables through rigorous and comprehensive screening. The results of this analysis suggested that hip or knee osteoarthritis is associated with an elevated risk of frailty. These results remained robust and consistent across multiple calculation methods, including inverse variance weighted (OR = 1.082, 95% CI: 1.0532-1.1125, p = 1.36 × 10^-8), MR-Egger regression (OR = 1.175, 95% CI: 1.0162-1.3604, p = 0.040), weighted median estimation (OR = 1.078, 95% CI: 1.0365-1.1219, p = 1.831 × 10^-4), weighted mode analysis (OR = 1.089, 95% CI: 1.0078-1.1771, p = 0.041) and simple mode analysis (OR = 1.093, 95% CI: 1.0112-1.1830, p = 0.034). Cochran's Q test showed no evidence of heterogeneity among the IV estimates derived from individual variants, and the MR-Egger regression analysis indicated that the presence of horizontal pleiotropy was unlikely to introduce bias into the results (intercept: -0.0044, p = 0.549).

Conclusions: Two-sample Mendelian randomization analysis effectively identified hip or knee osteoarthritis as a contributing risk factor for frailty.

Introduction: NOD-like receptor protein 3 (NLRP3) is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Here, we explored the role of NLRP3 in cigarette smoke (CS)-induced airway inflammation in COPD.

Material and methods: NLRP3 expression level was assessed with the microarray data in GEO datasets and validated in serum by ELISA from a case-control cohort. Male C57BL/6J mice were randomly divided into: saline, CS, MCC950 (a specific NLRP3 inhibitor, 10 mg/kg) and CS + MCC950 (5 mg/kg and 10 mg/kg) groups (n = 5 per group). All mice were exposed to CS or air for 4 weeks. Then, broncho-alveolar lavage (BAL) fluid and lung tissues were collected for cell counting, ELISA, HE staining and RNA sequencing with validation by real-time qPCR.

Results: Compared to non-smokers, NLRP3 expression was significantly elevated in the lung tissues and sera of COPD smokers. CS remarkably induced airway inflammation in mice, characterized by an increase of inflammatory cells and proinflammatory cytokines in BAL fluid and HE inflammatory score, which were ameliorated by MCC950 treatment dose-dependently. Subsequently, 84 candidate genes were selected following RNA sequencing, and five hub genes (Mmp9, IL-1α, Cxcr2, Cxcl10, Ccr1) were then identified by PPI and MCODE analyses, which were confirmed by real-time qPCR. GO and KEGG analysis suggested that the five genes were enriched in a complicated network of inflammatory processes and signaling pathways.

Conclusions: NLRP3 expression is elevated in lungs and sera of COPD smokers. Inhibition of NLRP3 significantly attenuates CS-induced airway inflammation in mice via inactivation of multiple hub genes and their related inflammatory processes and signaling pathways.

Introduction: We undertook an in-depth investigation of the data pertaining to pancreatic adenocarcinoma (PAAD) to identify potential targets for the development of precision therapies.

Material and methods: The construction of a protein-protein interaction (PPI) network was based on overlapping differentially expressed genes (DEGs) identified in the GSE16515, GSE32676, and GSE125158 datasets. A subsequent bioinformatic analysis was performed on the interconnected genes within the PPI network, leading to the identification of the central gene, CENPN. In vitro experimentation such as CCK8 and Transwell experiments was employed to elucidate the impact of CENPN expression patterns on PAAD cell proliferation, migration, and invasion. Furthermore, the investigation revealed through comprehensive enrichment analysis that the pivotal signaling pathway associated with CENPN is the p53 signaling pathway.

Results: Following a comprehensive bioinformatic analysis of 161 concordant differentially expressed genes (DEGs) across three microarray datasets, CENPN emerged as the central gene under investigation. Overexpression of CENPN in pancreatic adenocarcinoma (PAAD) was associated with unfavorable patient outcomes and heightened sensitivity to four PAAD therapies: gemcitabine, docetaxel, paclitaxel, and sunitinib. Reduced CENPN expression impeded PAAD cell proliferation, migration, and invasion; however, these effects were counteracted upon upregulation of CENPN expression. Additionally, CENPN interacted with MDM2, promoting PAAD progression by targeting the p53 signaling pathway.

Conclusions: The findings of our study substantiate that CENPN is associated with the pathogenesis of PAAD. Consequently, CENPN appears to be a promising candidate for targeted precision therapy in clinical applications.

Introduction: Mobile social media is a new type of online media that is participatory, open, and communicative, among other characteristics. Due to the increasing popularity of social media, this technology has become an indispensable part of people's social lives. This study aims to examine the relationship between childhood psychological maltreatment and social media addiction among university students as well as the mediating role of fear of missing out and the moderating effect of left-behind experience in this context.

Material and methods: A voluntary anonymous online survey of 1694 university students was conducted using the Childhood Psychological Maltreatment Scale, the Fear of Missing Out Scale, and the Social Media Addiction Scale.

Results: First, significant positive correlations were observed between childhood psychological maltreatment and both fear of missing out and social media addiction among university students. Fear of missing out partially mediated the relationship between childhood psychological maltreatment and social media addiction. Second, left-behind experience was found to moderate the direct path from childhood psychological maltreatment to social media addiction as well as the first half of the mediating effect of missed anxiety.

Conclusions: Childhood psychological maltreatment can predict social media addiction among university students not only directly but also indirectly through the mediating role of missed anxiety. The direct effect of childhood psychological maltreatment on social media addiction is moderated by left-behind experience. The first half of the mediating role of missed anxiety is also moderated by left-behind experience.

Introduction: There is insufficient evidence in statin on the treatment of Staphylococcus aureus (SA) infection, we observe and analyze the clinical outcomes and antibiotic resistance of SA bloodstream infections in patients who received statins.

Methods: A retrospective study was carried out in SA bloodstream infection of hospitalized patients from January 2018 to August 2023. The 30-day attributable mortality, 30-day all-cause mortality and clinical data of patients who received statins and non-statins were compared.

Results: A total of 74 patients with SA bloodstream infection were included, 32 (43.2%) patients received treatment with statins and 42 (56.8%) with non-statins. The incidence of methicillin-resistant SA (MRSA) was significantly lower in the statins group (15.6% vs. 38.1%, p = 0.034), however, no significant differences were observed in the mortality rate (p = 0.410).

Conclusions: This study revealed the superiority of statins in reducing incidence of MRSA among SA bloodstream infection patients, but statins do not improve the 30-day mortality rate.

Introduction: Fluid resuscitation of patients with sepsis is crucial. This study explored the role of fluid balance in the early resuscitation of sepsis patients in the intensive care unit (ICU).

Material and methods: A retrospective study of patients with sepsis using the Peking Union Medical College Hospital Intensive Care Medical Information System and Database from January 2014 to June 2020 was performed. Based on the survival status on day 28, the training cohort was divided into an alive group (n = 1,803) and a deceased group (n = 429). Univariate and multivariate analyses were used to identify risk factors, and the integrated learning XGBoost algorithm was used to construct a model for predicting outcomes. ROC and Kaplan-Meier survival curves were used to evaluate the effectiveness of the model. A verification cohort (n = 433) was used to verify the model.

Results: Univariate analysis showed that fluid balance is an important covariate. Based on the scatterplot distribution, a significant difference in mortality was determined between groups stratified with a balance of 1000 ml. There were associations in the multivariate analysis between poor outcomes and sex, PO₂/FiO₂, serum creatinine, FiO₂, platelets, respiratory rate, SPO₂, temperature, and total fluid volume (1000 ml). Among these variables, total fluid balance (1000 ml) had an OR of 1.98 (CI: 1.41-2.77, p < 0.001). Therefore, the model was built with these nine factors using XGBoost. Cross validation was used to verify generalizability. This model performed better than the SOFA and APACHE II models. The result was well verified in the verification cohort. A causal forest model suggested that patients with hypoxemia may suffer from positive fluid balance.

Conclusions: Sepsis fluid resuscitation in the ICU should be a targeted and goal-oriented treatment. A new prognostic prediction model was constructed and indicated that a 6-hour positive fluid balance after ICU initial admission is a risk factor for poor outcomes in sepsis patients. A 6-hour fluid balance above 1000 ml should be performed with caution.

Introduction: The study aimed to measure telomeres length (TL) and telomerase expression in normal endometrium and endometrial hyperplasia and cancer.

Methods: Total RNA and DNA were isolated from endometrium samples of 117 patients. The RT-PCR method was used to determine telomerase expression and relative telomere length.

Results: The control group had the longest telomeres in comparison to the hyperplasia and endometrial cancer groups. Only in the endometrial cancer group was telomerase expressed and positively correlated with telomere length.

Conclusions: Telomere extension in endometrial cancer is mediated by telomerase, but telomere length may not be an indicator of endometrioid cancer development.

Introduction: This study aimed to evaluate the anti-cancer effects of gedunin, a natural compound, in a rat model of gastric carcinogenesis induced by MNNG.

Methods: Fifty-four rats were randomly assigned to six groups for a 60-day study on the effects of MNNG and gedunin. Groups 1-4 received 200 mg/kg MNNG (1, 10, or 100 mg/kg), and group 5 had only 100 mg/kg gedunin.

Results: Gedunin at low doses exhibited anti-cancer and protective properties against MNNG-induced damage, including reduced inflammation, and apoptosis.

Conclusions: Gedunin demonstrates a U-shaped dose-response, with low doses offering protection and high doses promoting tumor growth.