[A case-control study on the relationship between the ratio of neutrophils to lymphocytes in malignant tumors and ventilator-associated pneumonia].

OBJECTIVE: To explore the relationship between ventilator-associated pneumonia (VAP) and neutrophil/lymphocyte ratio (NLR) before mechanical ventilation in patients with malignant tumors. METHODS: A retrospective nested case-control study was conducted. Patients with malignant tumor treated by mechanical ventilation admitted to the Third Affiliated Hospital of Guizhou Medical University from February 2015 to February 2020 were enrolled. The patients with VAP were selected as the case group, and the matched non-VAP cases were selected according to 1:2 as the control group. The clinical data were collected, and the differences of each index between the two groups were compared. The influencing factors of VAP in patients with malignant tumor were analyzed by multivariate Logistic regression. RESULTS: During the study period, 1 271 patients with malignant tumors were treated with mechanical ventilation, of which 241 cases had VAP, and the incidence of VAP was 18.96%. There were 232 VAP patients in the case group matched 464 non-VAP patients in the control group. The clinical data of age, gender, hospitalization diagnosis, primary tumor, regional lymph node and distant metastasis (TNM) stage, acute physiology and chronic health evaluation II (APACHE II), complications, duration of mechanical ventilation, hemoglobin (Hb) and serum albumin (Alb) levels were balanced and comparable between the two groups, and the cluster nursing measures were consistent. Compared with the control group, although there was no significant difference in neutrophil count (NEU) and lymphocyte count (LYM) in the case group [NEU (×109/L): 3.81±1.07 vs. 3.64±1.05, LYM (×109/L): 2.06±0.59 vs. 2.15±0.62, both P > 0.05], NLR was significantly increased (2.07±1.05 vs. 1.89±0.96, P < 0.05), and the hospital stay was significantly longer (days: 24.84±3.81 vs. 13.19±3.98, P < 0.01). NLR, gender, age, APACHE II score, TNM stage, Hb, serum Alb and duration of mechanical ventilation were included in multivariate Logistic regression analysis. The results showed that patients with elevated NLR had higher risk of VAP [odds ratio (OR) = 1.187, 95% confidence interval (95%CI) was 1.015-1.387, P = 0.032]. In patients with VAP, NLR was negatively correlated with the time of mechanical ventilation before VAP (r = -0.327, P = 0.000), and positively correlated with the time of treatment with antibiotics after VAP (r = 0.559, P = 0.000). CONCLUSIONS: Elevated NLR in patients with malignant tumors who were on mechanical ventilation can significantly increase the risk of VAP and increase the difficulty of treatment.

Mono-2-ethylhexyl phthalate induces the expression of genes involved in fatty acid synthesis in HepG2 cells.

Mono-2-ethylhexyl phthalate (MEHP) is a major bioactive metabolite in the widely used industrial plasticizer diethylhexyl phthalate (DEHP) that has been found to be toxic to the liver. The aim of this study is to determine whether MEHP exposure can change the expression of fatty acid metabolism-related genes in HepG2 cells, which might be related to non-alcoholic fatty liver disease (NAFLD). The results revealed that exposure to MEHP promoted lipid accumulation in HepG2 cells. The levels of intracellular triglycerides in the hepatocytes increased after exposure to 0.8-100 µM MEHP for 24 h and 48 h. The genetic expressions of SREBP-1c, ChREBP, ACC1, FASN, and SCD significantly increased at 6 h after exposure to MEHP. At 24 h, the expression of the SREBP-1c and ChREBP genes remained increased, while the expression of the FASN and SCD genes decreased. At 48 h, the expression of SREBP-1c, ChREBP, ACC1, FASN, and SCD decreased. Furthermore, the levels of proteins including ACC1, FASN, SCD, and ChREBP (except SREBP-1c) increased at 24 h. These findings suggest that MEHP exposure can promote fatty acid synthesis in hepatocytes by regulating the expression of relevant genes and proteins, contributing to NAFLD.

Formaldehyde alters triglyceride synthesis and very low-density lipoprotein secretion in a time-dependent manner.

Formaldehyde is a common indoor air pollutant that is toxic to the liver. This study aimed to investigate the effects of formaldehyde on triglyceride metabolism in human hepatocellular carcinoma cells (HepG2). Cell viability was detected using a MTT (3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide) assay. Following treatment with different concentrations of formaldehyde for 24 and 48h, the intra and extra-hepatocellular triglyceride (TG) content was determined using a chemical-enzymatic method; Western blotting was used to detect the levels of fatty acid synthesis and VLDL-related proteins. Our results showed that cell viability significantly decreased after formaldehyde treatment (0.5-12.5mM, 24/48h). Extracellular TG levels in the hepatocytes increased after formaldehyde treatment at 0.004mM-0.1mM for 24h. SREBP-1c, ACC, FASN, and MTP, CES3 and DGAT1 proteins increased significantly after 24h of formaldehyde treatment. Intracellular TG levels decreased for 48h treatment of formaldehyde. AMPKα increased significantly in all tested groups and p-AMPK increased significantly after 0.1mM formaldehyde treatment for 48h. Our results indicated that short-term formaldehyde exposure balances triglyceride metabolism by promoting hepatocellular TG synthesis and VLDL secretion; Long-term formaldehyde disturbs the TG metabolism balance in the hepatocytes.

Potential role of microRNA: identification and functional analysis of microRNA in corticospinal tract after unilateral lesions of the medullary pyramid.

Corticospinal tract is mainly descending tracts by dominating voluntary movement of the limbs and fine movement of distal limb, especially in mammals. Distal axonal degeneration is called anterograde degeneration. Proximal end is connected to the neuron cell body, whereas retrograde degeneration is very slight with the possibility of regeneration. MicroRNAs (miRNAs) are a short non-coding RNAs that regulate gene expression at the post-transcriptional level by binding with the 3' untranslated region of target mRNAs. In order to understand the mechanism of underlying gene alteration in the rostral and caudal, respectively, after the corticospinal tract injury, we analyzed rostral and caudal mRNA and miRNA, respectively, using microRNA and mRNA profiles. We combined the predicted targets of miRNA with differentially expressed mRNA for selecting intersection gene. To predict the function miRNAs, GO and KEGG enrichment analysis were performed to find genes associated with change of rostral and caudal, respectively. The bioinformatics analysis indicated that changes in miRNA and target mRNA expression affected rostral regeneration, including negative regulation of apoptosis, positive regulation of cell proliferation, cell adhesion, oligodendrocyte development etc. It also affected caudal degeneration, including induction of apoptosis, down-regulating nervous system development, immune response etc. The current results illustrated that corticospinal tract injury produces a wide range changes of miRNAs, whereas mRNA also showed significantly change which affects key biological processes after injury in rostral and caudal.

Biotinylated dextran amine anterograde tracing of the canine corticospinal tract.

In this study, biotinylated dextran amine (BDA) was microinjected into the left cortical motor area of the canine brain. Fluorescence microscopy results showed that a large amount of BDA-labeled pyramidal cells were visible in the left cortical motor area after injection. In the left medulla oblongata, the BDA-labeled corticospinal tract was evenly distributed, with green fluorescence that had a clear boundary with the surrounding tissue. The BDA-positive corticospinal tract entered into the right lateral funiculus of the spinal cord and descended into the posterior part of the right lateral funiculus, close to the posterior horn, from cervical to sacral segments. There was a small amount of green fluorescence in the sacral segment. The distribution of BDA labeling in the canine central nervous system was consistent with the course of the corticospinal tract. Fluorescence labeling for BDA gradually diminished with time after injection. Our findings indicate that the BDA anterograde tracing technique can be used to visualize the localization and trajectory of the corticospinal tract in the canine central nervous system.