Lipid metabolism-related gene prognostic index (LMRGPI) reveals distinct prognosis and treatment patterns for patients with early-stage pulmonary adenocarcinoma.

Background: Lipid metabolism plays a pivotal role in cancer progression and metastasis. This study aimed to investigate the prognostic value of lipid metabolism-related genes (LMRGs) in early-stage lung adenocarcinoma (LUAD) and develop a lipid metabolism-related gene prognostic index (LMRGPI) to predict their overall survival (OS) and treatment response. Methods: A total of 774 early-stage LUAD patients were identified from The Cancer Genome Atlas (TCGA, 403 patients) database and Gene Expression Omnibus (GEO, 371 patients) database. The non-negative Matrix Factorization (NMF) algorithm was used to identify different population subtypes based on LMRGs. The Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate Cox regression analyses were used to develop the LMRGPI, with receiver operating characteristic (ROC) curves and concordance index being used to evaluate its performance. The characteristics of mutation landscape, enriched pathways, tumor microenvironment (TME), and treatment response between different LMRGPI groups were also investigated. Results: We identified two population subtypes based on LMRGs in the TCGA-LUAD cohort, with distinct prognosis, TME, and immune status being observed. LMRGPI was developed based on the expression levels of six LMRGs, including ANGPTL4, NPAS2, SLCO1B3, ACOXL, ALOX15, and B3GALNT1. Higher LMRGPI was correlated with poor OS both in TCGA and GSE68465 cohorts. Two nomograms were established to predict the survival probability of early-stage LUAD, with higher consistencies being observed between the predicted and actual OS. Higher LMRGPI was significantly correlated with more frequent TP53 mutation, higher tumor mutation burden (TMB), and up-regulation of CD274. Besides, patients with higher LMRGPI presented unremarkable responses for gefitinib, erlotinib, cisplatin, and vinorelbine, while they tend to have a favorable response for immune checkpoint inhibitors (ICIs). The opposite results were observed in the low-LMRGPI group. Conclusions: We comprehensively investigated the prognostic value of LMRGs in early-stage LUAD. Given its good prognostic ability, LMRGPI could serve as a promising biomarker to predict the OS and treatment response of these patients.

Integration of Single-Cell RNA Sequencing and Bulk RNA Sequencing Data to Establish and Validate a Prognostic Model for Patients With Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) remains a lethal disease worldwide, with numerous studies exploring its potential prognostic markers using traditional RNA sequencing (RNA-seq) data. However, it cannot detect the exact cellular and molecular changes in tumor cells. This study aimed to construct a prognostic model for LUAD using single-cell RNA-seq (scRNA-seq) and traditional RNA-seq data. Methods: Bulk RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) database. LUAD scRNA-seq data were acquired from Gene Expression Omnibus (GEO) database. The uniform manifold approximation and projection (UMAP) was used for dimensionality reduction and cluster identification. Weighted Gene Correlation Network Analysis (WGCNA) was utilized to identify key modules and differentially expressed genes (DEGs). The non-negative Matrix Factorization (NMF) algorithm was used to identify different subtypes based on DEGs. The Cox regression analysis was used to develop the prognostic model. The characteristics of mutation landscape, immune status, and immune checkpoint inhibitors (ICIs) related genes between different risk groups were also investigated. Results: scRNA-seq data of four samples were integrated to identify 13 clusters and 9cell types. After applying differential analysis, NK cells, bladder epithelial cells, and bronchial epithelial cells were identified as significant cell types. Overall, 329 DEGs were selected for prognostic model construction through differential analysis and WGCNA. Besides, NMF identified two clusters based on DEGs in the TCGA cohort, with distinct prognosis and immune characteristics being observed. We developed a prognostic model based on the expression levels of six DEGs. A higher risk score was significantly correlated with poor survival outcomes but was associated with a more frequent TP53 mutation rate, higher tumor mutation burden (TMB), and up-regulation of PD-L1. Two independent external validation cohorts were also adopted to verify our results, with consistent results observed in them. Conclusion: This study constructed and validated a prognostic model for LUAD by integrating 10× scRNA-seq and bulk RNA-seq data. Besides, we observed two distinct subtypes in this population, with different prognosis and immune characteristics.

Clinical outcomes and prognostic factors in bloodstream infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae among patients with malignancy: a meta-analysis.

BACKGROUND: The colonization of Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) in bloodstream infections (BSIs) has been increased dramatically worldwide, and it was associated with worse clinical outcomes in patients with malignancy. We performed the meta-analysis to investigate the prognosis and risk factors in BSIs caused by ESBL-PE in oncological patients. METHODS: PubMed, EMBASE, and Cochrane Library were searched for related studies. All-cause mortality was considered as the primary outcome. Subgroup analyses, meta-regression analyses, and sensitivity analysis were used to investigate heterogeneity and reliability in results. RESULTS: 6,729 patients from 25 studies were eligible. Six studies enrolled oncological patients with BSIs caused by ESBL-PE only, while 19 studies both enrolled ESBL-PE and non-ESBL-PE infections. The results showed that BSIs caused by ESBL-PE in patients with malignancy was associated with higher mortality than non-ESBL-PE infections (RR = 2.21, 95% CI: 1.60-3.06, P < 0.001), with a significant between-study heterogeneity (I2 =78.3%, P < 0.001). Subgroup analyses showed that children (RR = 2.80, 95% CI: 2.29-3.43, P < 0.001) and hematological malignancy (RR = 3.20, 95% CI: 2.54-4.03, P < 0.001) were associated with a higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality. CONCLUSIONS: Our study identified that BSIs caused by ESBL-PE in patients with malignancy were associated with worse clinical outcomes compared with non-ESBL-PE infections. Furthermore, children and hematological malignancy were associated with higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality.

The Effect of Thymoquinone on the Characteristics of the Brain Extracellular Space in Transient Middle Cerebral Artery Occlusion Rats.

The extracellular space (ECS) is the space between the neurons and the capillaries in the brain. The volume fraction (α) and the tortuosity (λ) are the main parameters used to describe its characteristics. Thymoquinone has been proved to possess anti-oxidant and anti-inflammatory activity. In this study, we used a gadolinium-diethylenetriaminepentacetate (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) system to determine the effects of thymoquinone on ECS parameters in transient middle cerebral artery occlusion rats (tMCAO) to prove the neuroprotective effect of thymoquinone on brain tissue damage caused by ischemic stroke. Neurological examinations, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining and assaying of ECS parameters using MRI were performed 24 h after surgery. We found that thymoquinone could improve the behavioural performance by neurological examinations. TTC staining indicated that thymoquinone significantly decreased the percentage of hemi-cerebral infarction. Also, H&E staining showed that thymoquinone could inhibit the neuron necrosis in the hippocampal CA1 region. We found that thymoquinone treatment could inhibit the changes in ECS diffusion parameters, which might prove that thymoquinone might protect brain tissue damage caused by ischemic stroke. Thymoquinone can protect the brain against cerebral ischemia-reperfusion injury, effectively ameliorate abnormalities in characteristics of ECS and decrease cerebral infarction in tMCAO rats.

Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI.

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism.

Effects of Dl-3-n-butylphthalide on Cerebral Ischemia Infarction in Rat Model by Mass Spectrometry Imaging.

Dl-3-n-butylphthalide (NBP) is a drug that is used in the treatment of ischaemic stroke. However, to the best of our knowledge, there are no systematic studies investigating the effects of dl-3-n-butylphtalide on the brain metabolism of small molecules. In this study, we first investigated the effects of dl-3-n-butylphthalide on the spatial distribution of small molecules in the brains of rats with permanent middle cerebral artery occlusion (pMCAO) using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) imaging. After pMCAO modelling or a sham operation, rats were given four mg/kg of dl-3-n-butylphthalide through the caudal vein or saline once a day for nine days. The degree of neurological deficit in rats was evaluated using the modified neurological severity score (mNSS). MALDI-TOF-MS imaging was used to observe the content and distribution of small molecules related to metabolism during focal cerebral ischaemia. Multiple reaction monitoring (MRM) mode with liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to verify the results obtained from MALDI-TOF-MS imaging. These small molecules were found to be involved in glucose metabolism, ATP metabolism, the glutamate-glutamine cycle, malate aspartate shuttle, oxidative stress, and inorganic ion homeostasis. Of the 13 metabolites identified by MALDI-TOF-MS imaging, seven compounds, ATP, ADP, AMP, GMP, N-acetylaspartic acid, ascorbic acid and glutathione, were further validated by LC-MS/MS. Taken together, these results indicate that dl-3-n-butylphthalide significantly improved ATP metabolism, level of antioxidants, and sodium-potassium ion balance in a rat model of pMCAO.