The current study elucidated the role of a long non‐coding RNA (lncRNA), FOXD2‐AS1, in the pathogenesis of hepatocellular carcinoma (HCC) and the regulatory mechanism underlying FOXD2‐AS1/miR‐150‐5p/transmembrane protein 9 (TMEM9) signalling in HCC. Microarray analysis was used for preliminary screening of candidate lncRNAs in HCC tissues. qRT‐PCR and Western blot analyses were used to detect the expression of FOXD2‐AS1. Cell proliferation assays, luciferase assay and RNA immunoprecipitation were performed to examine the mechanism by which FOXD2‐AS1 mediates sorafenib resistance in HCC cells. FOXD2‐AS1 and TMEM9 were significantly decreased and miR‐150‐5p was increased in SR‐HepG2 and SR‐HUH7 cells compared with control parental cells. Overexpression of FOXD2‐AS1 increased TMEM9 expression and overcame the resistance of SR‐HepG2 and SR‐HUH7 cells. Conversely, knockdown of FOXD2‐AS1 decreased TMEM9 expression and increased the sensitivity of HepG2 and Huh7 cells to sorafenib. Our data also demonstrated that FOXD2‐AS1 functioned as a sponge for miR‐150‐5p to modulate TMEM9 expression. Taken together, our findings revealed that FOXD2‐AS1 is an important regulator of TMEM9 and contributed to sorafenib resistance. Thus, FOXD2‐AS1 may serve as a therapeutic target against sorafenib resistance in HCC.
Background: Nosocomial meningitis with multidrug-resistant (MDR) or extensively drug-resistant (XDR) Acinetobacter baumannii is a life-threatening complication in neurosurgery. Treatment of these infections is challenging because of poor penetration of the available antibiotics into the cerebrospinal fluid (CSF). Intrathecal (ITH) or intraventricular (IVT) administration of antibiotics is increasingly used as the last treatment option against MDR/XDR Gram-negative bacteria meningitis not responding to intravenous (IV) regimens. However, pertinent data in pediatric patients is scarce.Case Presentation: A 14-year-old male patient developed meningitis from an MDR strain of A. baumannii following endoscopic endonasal resection of craniopharyngioma. Despite a combination therapy involving IV tigecycline, we observed clinical and bacteriologic failure. The patient was then successfully treated with an ITH and IV polymyxin B-based combination. Quantification of tigecycline and polymyxin B in CSF was performed with two-dimensional high-performance liquid chromatography (2D-HPLC) and HDLC coupled with tandem mass spectrometry (HPLC-MS/MS), respectively. Adverse drug reactions (neurotoxicity and skin hyperpigmentation), probably induced by polymyxin B, were acceptable and reversible.Conclusions: The case illustrates ITH and IV Polymyxin B-based combination is an optimal therapeutic option against MDR A. baumannii meningitis in this pediatric patient. In the future, real-time PK/PD data obtained from patients during ITH/IVT polymyxin B therapy should be required to optimize polymyxin use with maximal efficacy and minimal adverse effects.
The estimated glucose disposal rate (eGDR), as a novel metric of insulin resistance (IR), has been demonstrated to correlate with hepatic steatosis in patients with diabetes. Although IR is considered as a factor affecting lipid metabolism, the correlation between eGDR and metabolic associated fatty liver disease (MAFLD) is still unclear. Data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) were employed in this cross-sectional study designed to examine the association between eGDR and MAFLD through the application of weighted multivariate logistic regression model. The nonlinear relationship was described utilizing restricted cubic spline (RCS). Subgroup analysis was performed to assess the consistency of the results and causal mediation analysis was employed to explore potential mediators. The study included 3,585 participants, 2,002 of whom diagnosed MAFLD, with a prevalence rate of 55.84%. After adjusting for all confounding factors, the risk of MAFLD decreased by 19% with each unit increase in the eGDR (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.76, 0.88, P < 0.0001). Analysis of eGDR in quartiles further supported this finding. The restricted cubic spline analysis revealed a significant nonlinear negative association between eGDR and MAFLD. Causal mediation analysis indicated that the relationship between eGDR and MAFLD was partially mediated by the atherogenic index of plasma (AIP), with a mediation ratio of 8.75%. Our results demonstrate that eGDR has a significant nonlinear negative association with the prevalence of MAFLD, in which AIP plays a mediating role, offering new insights into the prevention and management of MAFLD.
Objective. To develop and authenticate a risk stratification framework and nomogram for ascertaining cancer-specific survival (CSS) among the pediatric brainstem gliomas. Methods. For patients less than 12 years, according to Surveillance, Epidemiology, and End Results (SEER), information from 1998 to 2016 is found in their databases. The survival outcomes, treatments, and demographic clinicopathologic conditions are scrutinized per the database validation, and training cohorts are divided and validated using multivariate Cox regression analysis. A nomogram was designed, and predominantly, the risk stratification conceptualization engaged selected tenets according to the multivariate analysis. The model’s authenticity was substantiated through C-index measure and calibration curves. Results. There are 806 pediatric concerns of histologically concluded brainstem glioma in the research. According to multivariate analysis, age, grade, radiotherapy, and race (with value < 0.05) depicted independent prognostic variations of the pediatric gliomas. The nomogram’s C-index was approximately 0.75 and an accompanied predictive capability for CSS. Conclusion. The nomogram constructed in this glioma’s context is the primary predictor of using risk stratification. A combination of nomograms with the risk stratification mechanism assists clinicians in monitoring high-risk individuals and engage targeted accessory treatment.