Sertraline Hydrochloride Overdose Resulting in Diabetes Insipidus: A Case Report.

Sertraline hydrochloride belongs to the selective serotonin reuptake inhibitor class of antidepressants, which can cause respiratory depression, hypotension, malignant vomiting, liver function impairment, and other symptoms when taken in excess. To our knowledge, reports of sertraline hydrochloride overdose causing diabetes insipidus in patients are rare. This report describes a unique case of a 17-year-old female patient who developed diabetes insipidus after a one-time oral intake of 20 sertraline hydrochloride tablets (50 mg/tablet) during the later course of treatment. Her symptoms were effectively relieved after treatment with pituitrin.

Lixisenatide ameliorated lipopolysaccharide (LPS)-induced expression of mucin and inflammation in bronchial epithelial cells.

Chronic obstructive pulmonary disease (COPD) induces serious social and economic burdens due to its high disability and mortality, the pathogenesis of which is highly involved with inflammation, oxidative stress (OS), and mechanism of mucin 5AC (MUC5AC) secretion. Lixisenatide is a selective glucagon-like peptide 1 receptor agonist recently reported to have anti-inflammatory properties. Our study will focus on the potential impact of lixisenatide on lipopolysaccharide (LPS)-induced mucin secretion and inflammation in 16 human bronchial epithelial (16HBE) cells to check its potential function in COPD. 16HBE cells were treated with LPS, with or without lixisenatide (10 and 20 nM) for 1 day. Remarkably declined cell viability, enhanced lactate dehydrogenase release, activated OS, and elevated release of inflammatory cytokines were observed in LPS-treated 16HBE cells, accompanied by the activation of nuclear factor-κB signaling, all of which were signally reversed by lixisenatide. Moreover, elevated expression and release of MUC5AC were observed in LPS-treated 16HBE cells but were markedly repressed by lixisenatide. Furthermore, the repressed nuclear factor erythroid 2-related factor 2 (Nrf2) level in LPS-treated 16HBE cells was notably rescued by lixisenatide. Lastly, following the knockdown of Nrf2, the protective function of lixisenatide on LPS-triggered MUC5AC release in 16HBE cells was significantly abrogated. Collectively, lixisenatide ameliorated LPS-induced expression of mucin and inflammation in bronchial epithelial cells by regulating Nrf2.

Single-cell combined bioinformatics analysis: construction of immune cluster and risk prognostic model in kidney renal clear cells based on CD8+ T cell-associated genes.

BACKGROUND: Kidney cancer is an immunogenic solid tumor, characterized by high tumor burden and infiltration of CD8+ T cells. Although immunotherapy targeting the PD1/CTLA-4 axis has demonstrated excellent clinical efficacy, clinical outcomes in most patients are poor. METHODS: We used the RNA sequencing data from the GEO database for KIRC GSE121636 and normal kidney tissue GSE131685, and performed single-cell analysis for cluster identification, pathway enrichment, and CD8+ T cell-associated gene identification. Subsequently, the significance of different CD8+ T-cell associated gene subtypes was elucidated by consensus clustering, pathway analysis, mutated gene analysis, and KIRC immune microenvironment analysis in the TCGA-KIRC disease cohort. Single gene analysis identified LAG3 as the most critical CD8+ T-cell-associated gene and its function was verified by cell phenotype and immunohistochemistry in KIRC. RESULTS: In the present study, CD8+ T-cell associated genes in KIRC were screened, including GZMK, CD27, CCL4L2, FXYD2, LAG3, RGS1, CST7, DUSP4, CD8A, and TRBV20-1 and an immunological risk prognostic model was constructed (risk score = - 0.291858656434841*GZMK - 0.192758342489394*FXYD2 + 0.625023643446193*LAG3 + 0.161324477181591*RGS1 - 0.380169045328895*DUSP4 - 0.107221347575037*TRBV20-1). LAG3 was identified and proved as the most critical CD8+ T cell-associated gene in KIRC. CONCLUSION: We proposed and constructed an immunological risk prognostic model for CD8+ T cell-associated genes and identified LAG3 as a pivotal gene for KIRC progression and CD8+ T-cell infiltration. The model comprehensively explained the immune microenvironment and provided novel immune-related therapeutic targets and biomarkers in KIRC.

LMNTD2-AS1 regulates immune cell infiltration and promotes prostate cancer progression by targeting FUS to regulate NRF2 signal pathway.

Numerous studies have demonstrated that long non-coding RNAs (lncRNAs) play crucial roles in tumor progression. This study aimed to identify lncRNAs associated with overall survival (OS) and progression-free interval (PFI) in prostate cancer (PCa) patients and to elucidate the driving mechanisms and functions of these lncRNAs. We utilized the TCGA database to screen for lncRNAs linked with OS and PFI. KM survival analysis, ROC curve analysis, and Cox survival analysis were employed to assess the prognostic significance of lncRNAs in PCa patients. We conducted a loss-of-function assay to explore the role of lncRNAs in PCa. Correlation analysis was performed to study the relationship between lncRNAs and immune cell infiltration. Lasso regression analysis was performed to screen proteins which might interact with lncRNAs, while rescue experiments verified the integrity of the signaling pathway. LMNTD2-AS1 was found to be the only lncRNA in PCa patients associated with both OS and PFI with significantly elevated levels in PCa. Elevated LMNTD2-AS1 expression was significantly linked to advanced stage, grade, primary treatment outcomes, residual tumors, and Gleason scores in PCa patients. Moreover, multivariate Cox regression analysis revealed that high LMNTD2-AS1 expression independently predicted PFI in PCa patients. The AUC of LMNTD2-AS1 for predicting 3-year OS and 5-year OS in PCa patients was 0.877 and 0.807, respectively, while for 3-year PFI and 5-year PFI it was 0.751 and 0.727, respectively. Overexpression of LMNTD2-AS1 correlated with infiltration of neutrophils, macrophages, pDC, NK CD56bright cells, and other immune cells. Furthermore, FUS and NRF2 are both potential binding proteins and related signaling pathways downstream of LMNTD2-AS1. Functional experiments demonstrated that LMNTD2-AS1 knockdown significantly inhibited migration, invasion, and proliferation of PCa cells while overexpression of FUS was found to rescue the functional inhibition caused by LMNTD2-AS1 knockdown. LMNTD2-AS1 functions as an oncogene in PCa, influencing patient prognosis and the immune microenvironment; it may regulate immune cell infiltration and promote PCa progression by interacting with the NRF2 signaling pathway via FUS binding.

Risk factors for surgical compliance and impact on the survival of patients with glioma: a population-based propensity score-matched study.

PURPOSE: To comprehensively analyze the impact of surgical compliance on the survival of patients with glioma and to explore the factors that influence surgical compliance. METHODS: Clinical data of patients with glioma between 2004 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier curves and Cox regression were used to analyze the effect of surgical compliance on overall survival (OS) and disease-specific survival (DSS). Multivariate Cox regression was used to select the prediction variables and construct the nomograms. The predictive power of these models was assessed using Harell's consistency index (C-index), decision curve analysis (DCA), receiver operating characteristic (ROC) curves, and calibration curves. Multivariate logistic regression was performed to analyze the related variables of surgical compliance, and 1:1 propensity score matching (PSM) was applied to evaluate the validity of the results of patients with favorable and poor surgical compliance. RESULTS: Among the 47,573 eligible glioma patients recommended for surgery, 46,380 (97.5%) were in the surgical compliance group, while 1193 (2.5%) were in the noncompliance group. Surgical compliance was an independent prognostic factor for glioma patients, as indicated by multivariate Cox regression analysis that patients with surgical compliance had worse OS (hazard ratio [HR] 1.924; 95% confidence interval [CI] 1.800-2.056, p < 0.001) and DSS (HR 1.718; 95% CI 1.592-1.853, p < 0.001) in comparison to those without surgical compliance. A nomogram was developed and internally validated to be able to predict glioma prognosis. The nomogram can well predict patients' OS (C-index: 0.745) and DSS (C-index: 0.744). ROC curve, DCA curve, and calibration curve were applied to further assess the accuracy of the nomogram. Poor surgical compliance was found to be related to older age, female gender, tumor diameter, grade II or higher, poor grading, tumor location in the cerebellum and brainstem, and low household income. CONCLUSION: Surgical compliance is an independent prognostic factor for predicting the OS and DSS of patients with glioma, and good surgical compliance was significantly related to good survival.