The First People's Hospital of Zhaoqing

Ferroptosis constitutes a pivotal pathological event following spinal cord injury and presents substantial challenges to the restoration of neurological function. Cystine-glutamate transporter SLC7A11 is essential for maintaining cellular redox homeostasis and resisting ferroptosis. However, the mechanisms underlying neuronal ferroptosis caused by SLC7A11 downregulation following spinal cord injury remain unclear. Herein, we provide evidence that tumor protein 53, a negative regulator of SLC7A11, was significantly upregulated post-spinal cord injury. Transcriptomic analysis indicated that tumor protein 53 was associated with injury severity. We subsequently confirmed that tumor protein 53 inhibition restored the expressions of SLC7A11 and glutathione peroxidase 4, alleviated neuronal ferroptosis, and improved neurological function in a contusion spinal cord injury rat model. The regulatory effects of tumor protein 53 on the transcription and ubiquitination of SLC7A11 were further elucidated using chromatin immunoprecipitation polymerase chain reaction and cleavage under targets and tagmentation techniques. Additionally, Kelch-like protein 4, an E3 ubiquitin ligase adaptor, was demonstrated to play an important role in the tumor protein 53-mediated ubiquitination of SLC7A11. In summary, the present study elucidated the possible mechanisms of tumor protein 53-mediated neuronal ferroptosis in spinal cord injury, thereby providing potential targets and insights for clinical translation.

Recent research indicates that insulin resistance (IR) plays a role in the progression of cardiovascular diseases (CVD), with the estimated glucose disposal rate (eGDR) recognized as a dependable proxy for measuring IR. Nonetheless, there is a scarcity of studies concentrating on overweight and obese populations. Consequently, this study aims to explore the correlation between eGDR and the risk of developing CVD among individuals who are overweight or obese. In the cohort study, participants were selected from the China Health and Retirement Longitudinal Study (CHARLS), encompassing those without a history of heart disease and possessing complete baseline data on the estimated glucose disposal rate (eGDR). Participants were stratified into three groups based on the tertiles (T) of eGDR values. Cox proportional hazards models were used to evaluate the association between eGDR and the incidence of heart disease. Furthermore, a multivariate adjusted restricted cubic spline (RCS) model was utilized to assess the linearity of the association. Robustness of the results was examined through subgroup and sensitivity analyses. A cohort of 2,217 participants were enrolled, with a mean age of 56.9 ± 8.0 years, including 839 males (37.8%). Throughout a follow-up duration of up to 9 years, 600 participants (27.1%) developed heart disease events. After controlling for all covariates (Model 4), the association between eGDR and incidence heart disease persisted as significant (adjusted HR: 0.90; 95% CI: 0.86–0.94; P < 0.001). When analyzed as a categorical variable, eGDR tertiles 2 and 3 demonstrated a significant reduction in the risk of heart disease compared to tertile 1, with adjusted HRs of 0.76 (95% CI: 0.62–0.92) and 0.56 (95% CI: 0.44–0.71), respectively, in Model 4. RCS analysis indicated an inverse linear relationship was observed between eGDR and the occurrence of heart disease. Subgroups and sensitivity analysis both verify the robustness of the findings. eGDR is a practical and informative marker for identifying individuals with overweight or obesity who are at higher risk of heart disease. Incorporating eGDR into routine risk assessment may help improve early prevention strategies. Further validation in external cohorts is warranted.

High rates of migration and invasiveness are crucial factors contributing to the elevated mortality associated with liver cancer. Peptidyl-prolyl isomerase A (PPIA) has emerged as a key player in the progression of various human cancers, although its specific role in the advancement of liver cancer has not been fully elucidated. Previous research revealed that PPIA dictated nuclear factor E2-related factor 2 (Nrf2) stability to promote cancer progression. To clarify this by exploring the biological effects of PPIA and Nrf2 in liver cancer. First, PPIA and Nrf2 expression in normal hepatocyte cells and human hepatoma cells were quantitatively analyzed using RT-qPCR and western blot. Then, to assess effects of PPIA on migration and invasion of hepatoma cells, the study employed the scratch assay and the transwell invasion assay. Further, PPIA and Nrf2 were knock-downed, and ferroptotic cell death was assessed in erastin-treated hepatoma cells to clarify effect mechanism of PPIA in liver cancer progression. The interaction between PPIA and Nrf2 by conducting Co-IP experiments. The findings of our research indicate that PPIA is overexpressed, and promotes proliferation, migration and invasion in human hepatoma cells. The knockdown of PPIA and Nrf2 significantly enhances ferroptosis, which subsequently leads to a marked decrease in both migration and invasion of human hepatoma cells. Furthermore, our investigation revealed that PPIA interacts with Nrf2 in hepatoma cells, suggesting a complex relationship between these two proteins in the progression of liver cancer. This study highlights the potential role of PPIA as a critical oncogenic driver in liver cancer, suggesting that targeting PPIA could offer therapeutic advantages in the treatment of this malignancy.

The post-coronavirus disease 2019 (COVID-19) pulmonary sequelae have garnered public concern. We conducted a multicenter cross-sectional study in outpatient and health exam populations from 23 clinical centers (including university-affiliated/provincial general hospitals, municipal general hospitals, county hospitals, and specialized hospitals) in China (2019-2023), to assess temporal trends and potential influencing factors in the detection of CT-diagnosed pulmonary nodules, pleural effusion, pneumonia, and suspected lung tumors, cancer and viral pneumonia, clarifying pandemic impacts on lung health. Dynamic comparisons across key phases including initial outbreak, vaccine rollout, population-wide vaccination, and major adjustment of pandemic control policies, were performed. This study analyzed 1,616,750 clinical samples (1,102,605 outpatient, 514,145 health examination; 885,945 males, 730,805 females). Pulmonary nodule detection rose progressively, with surges in 2020-2021 and 2023, plateauing in 2021-2022. Outpatients and males showed steeper increases. University-affiliated/provincial hospitals had sharpest increases vs. municipal and county tiers. Specialized hospitals matched general hospital rates. AI boosted detection rates. CT-suspected lung tumors/cancer remained low and stable, unrelated to nodule trends. These results underscore 2019-2023 pulmonary nodule detection surges linked to SARS-CoV-2 infections and AI adoption. COVID-19 vaccination did not accelerate detection but may have slowed it short-term. Long-term studies on infection, vaccine impacts and pandemic-detected nodules' outcomes are urgently needed.

This study aims to assess the impact of general anesthesia versus epidural anesthesia on clinical outcomes in elderly orthopedic patients undergoing lower limb surgeries. This retrospective study included patients aged ≥ 75 years who underwent hip, knee, and femoral shaft surgeries at the Third Affiliated Hospital of Sun Yat-sen University. Patients were divided into two groups based on the anesthetic technique: general anesthesia group and epidural anesthesia group. Patient demographic information, intraoperative clinical parameters, and postoperative complications were collected through the medical record system, and logistic regression analysis was used to explore the impact of anesthesia type on postoperative complications. Patients in the epidural anesthesia group had better postoperative recovery compared to the general anesthesia group, as evidenced by shorter stay times in the post-anesthesia care unit (PACU) and lower intensive care unit (ICU) admission rates. The incidence of postoperative pulmonary infection (5.8% vs. 14.5%) and complications (7.3% vs. 16.4%) was significantly lower in the epidural anesthesia group compared to the general anesthesia group. Additionally, logistic regression analysis showed that the risk of postoperative pulmonary infection was significantly higher in the general anesthesia group (OR = 2.208, 95% CI: 1.050-5.135), and the risk of pulmonary complications was also increased (OR = 1.793, 95% CI: 1.080-3.982). In contrast, no significant differences were observed between the two groups in postoperative pain management or cardiovascular-related complications. For orthopedic patients aged 75 years and older, epidural anesthesia provides significant advantages in terms of postoperative recovery, particularly in reducing postoperative pulmonary infections and complications. General anesthesia was associated with a higher risk of these adverse outcomes. Therefore, epidural anesthesia may be a safer option for high-risk elderly patients undergoing lower limb orthopedic surgery.

Plasma fibrinogen is essential in thrombosis and fibrinolysis, yet its dynamic changes pre- and post-intravenous thrombolysis (IVT) for predicting brain injury severity and prognosis in acute ischemic stroke (AIS) patients remain unclear. This study examined how fibrinogen trends before and after IVT correlate with brain injury severity and clinical outcomes in IVT-treated patients. This multicenter study prospectively enrolled AIS patients treated with IVT at 16 hospitals and recorded their fibrinogen trends before and after thrombolysis. Levels of brain injury markers were measured to represent the extent of brain injury, including glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1), S100β, and neuron-specific enolase (NSE). Prognostic indicators included early neurological deterioration (END), hemorrhagic transformation, infarct volume, National Institutes of Health Stroke Scale (NIHSS) score at 7 days, 3-month poor outcome (modified Rankin Scale [mRS] score > 1), and mortality. A total of 827 patients were enrolled, with 207 exhibiting elevated fibrinogen levels 24 h after IVT. Patients with elevated fibrinogen levels exhibited significantly higher levels of brain injury markers (GFAP, UCH-L1, S100β), larger infarct volumes, higher NIHSS scores at 7 days, and a higher incidence of END and poor outcomes compared to those with non-elevated fibrinogen levels. Both univariate and multivariate analyses identified elevated fibrinogen levels after IVT as an independent predictor of severe brain injury, larger infarct volume, higher NIHSS score, occurrence of END, and poor outcomes. Elevated fibrinogen levels 24 h after IVT are independently associated with more severe brain injury and worse clinical outcomes in AIS patients.

This research aimed to develop and validate a novel nomogram for predicting overall survival (OS) in Dedifferentiated liposarcoma (DDLPS) patients. A retrospective cohort of 1,155 DDLPS cases diagnosed from 2004 to 2015 was identified throughthe Surveillance, Epidemiology, and End Results (SEER) registry.The prognostic model was subsequently developed by incorporatingcovariates independently associated with survival outcomes,as determined through multivariate analysis.To assess the model's predictive performance and clinical utility, we employeda suite of validation metrics. Cox regression revealed age, tumor size, laterality, AJCC stage, combined summary stage, radiation, chemotherapy, and surgery as independent predictive variables for DDLPS. The C-index of the nomogram in the training and validation cohorts was 0.708 and 0.704, which was higher than that of the AJCC system. All AUC values、NRI (> 50%), IDI (> 10%), calibration and DCA curves showed that the new model had an excellent ability to predict OS. Our study represents the initial effort to develop a nomogram for predicting OS in DDLPS patients based on the SEER database. Significantly, the nomogram showed a greater potential for accurately predicting survival as opposed to the AJCC system.

BACKGROUNDDiabetic kidney disease (DKD) has become the leading cause of end-stage renal disease. The disease characteristics, morbidity, and renal function progression rate of patients with DKD are all related to sex. This suggests that sex hormones may play an important role in changing renal function in patients with diabetes. There have been only a few studies on the correlation between sex hormones and DKD, which have contradictory conclusions.AIMTo investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus (T2DM).METHODSThis retrospective cross-sectional study included 356 patients with T2DM. Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices. By adjusting for age, body mass index, systolic blood pressure, diastolic blood pressure, duration of diabetes, use of sodium-glucose cotrasporter-2 inhibitor, use of glucagon-like peptide-1 receptor agonist, hypertension, use of angiotensin-converting enzyme inhibitor/ angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, diabetic retinopathy, diabetic peripheral vascular disease, triglyceride, uric acid, and hemoglobin A1c, multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio (UACR) and DKD.RESULTSIn men, dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors [regression coefficient (β) = -0.691, 95% confidence interval (CI): -1.241 to -0.141 for quartile 4 vs quartile 1; P = 0.006 for trend]. Elevated levels of estradiol were positively associated with DKD [odds ratio (OR) = 3.097, 95%CI: 1.083-8.856 for quartile 4 vs quartile 1; P = 0.041 for trend], and higher luteinizing hormone (LH) levels were similarly associated with DKD (OR = 4.164, 95%CI: 1.30-13.330 for quartile 4 vs quartile 1; P = 0.048 for trend). In postmenopausal women, LH levels were positively correlated with log-transformed UACR and DKD (β = 1.039, 95%CI: 0.284-1.794 for quartile 4 vs quartile 1; P = 0.006 for trend and OR = 15.117, 95%CI: 2.191-104.326 for quartile 4 vs quartile 1; P = 0.004 for trend). Follicle-stimulating hormone (FSH) levels were also positively associated with DKD (OR = 9.588, 95%CI: 1.680-54.709 for quartile 4 vs quartile 1; P = 0.014 for trend).CONCLUSIONIn men with T2DM, elevated levels of estradiol and LH levels were positively associated with increased risk of DKD. In postmenopausal women with T2DM, high FSH and LH levels were positively associated with increased risk of DKD.