Utility of the triglyceride-glucose index for predicting restenosis following revascularization surgery for extracranial carotid artery stenosis: A retrospective cohort study.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are effective interventions for treating extracranial carotid artery stenosis (ECAS), but long-term prognosis is limited by postoperative restenosis. Carotid restenosis is defined as carotid stenosis >50% by various examination methods in patients after carotid revascularization. This retrospective cohort study examined the value of the triglyceride-glucose (TyG) index for predicting vascular restenosis after carotid revascularization. METHODS: A total of 830 patients receiving CEA (408 cases, 49.2%) or CAS (422 cases, 50.8%) were included in this study. Patients were stratified into three subgroups according to TyG index tertile (high, intermediate, and low), and predictive value for restenosis was evaluated by constructing multivariate Cox proportional hazard regression models. RESULTS: Incidence of postoperative restenosis was significantly greater among patients with a high TyG index according to univariate analysis. Kaplan-Meier survival curve analysis revealed a progressive increase in restenosis prevalence with rising TyG index. Multivariate Cox regression models also identified TyG index as an independent predictor of restenosis, while receiver operating characteristic (ROC) curve analysis showed that TyG index predicted restenosis with moderate sensitivity (57.24%) and specificity (67.99%) (AUC: 0.619, 95% CI 0.585-0.652, z-statistic=4.745, p<0.001). Addition of the TyG index to an established risk factor model incrementally improved restenosis prediction (AUC: 0.684 (0.651-0.715) vs 0.661 (0.628-0.694), z-statistic =2.027, p = 0.043) with statistical differences. CONCLUSION: The TyG index is positively correlated with vascular restenosis risk after revascularization, which can be used for incremental prediction and has certain predictive value.

A study of grief experience interviews with family members of patients with advanced malignant tumors based on noninvasive death index monitoring.

OBJECTIVE: To explore the grief experiences of family members of patients with advanced malignant tumors before and after death. METHODS: This study used both quantitative and qualitative research methods. A total of 10 people with family members with terminal malignant tumors were chosen and assessed five times according to a specific non-invasive mortality index and the Distress Thermometer scale. Additionally, the participants attended an in-depth interview. RESULTS: The grief experiences of the bereaved included their knowledge of and attitude towards death, the physical and mental conditions of the family members of patients in the terminal stage, the needs of family members, and the response to death and growth of those family members. CONCLUSIONS: The grief experience interviews of family members of patients with advanced malignant tumors are universal. It is suggested that the nursing staff should pay attention to the emotional experience of the bereaved after the death of the patient throughout the whole nursing process, including the continuous follow-up during the home period. It is hoped that the implementation of grief counseling methods in the later stage can help the bereaved to successfully go through the grieving period, prevent grief disorders, and help them return to society.

Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration and Invasion.

OBJECTIVES: Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC. MATERIALS AND METHODS: Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman's rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay. RESULTS: In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01)/clinical staging (r = -0.41, P<0.01)/tumor stage (r = -0.28, P = 0.02)/nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells. CONCLUSION: Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC.

Inhalation of glycopyrronium inhibits cigarette smoke-induced acute lung inflammation in a murine model of COPD.

Glycopyrronium bromide (GB) is a muscarinic receptor antagonist that has been used as a long-acting bronchodilator in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate the anti-inflammatory activity of inhaled GB in a cigarette smoke-induced acute lung inflammation mouse model. We found that aerosol pre-treatment with GB suppresses the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) in cigarette smoke (CS)-exposed mice. GB at doses of 300 and 600 µg/ml significantly inhibited the CS-induced increases in the mRNA and protein expression levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-ß1 in lung tissues and the BALF. Moreover, GB at a dose of 600 µg/ml significantly inhibited the CS-induced changes in glutathione (GSH) and myeloperoxidase (MPO) activities in the BALF, decreased the CS-induced expression of matrix metalloproteinases (MMP)-9, and increased the CS-induced expression of tissue inhibitor of metalloproteinases (TIMP)-1, as determined through the immunohistochemical staining of lung tissue. Our results demonstrate the beneficial effects of inhaled GB on the inflammatory reaction in COPD.

Apple polyphenol protects against cigarette smoke-induced acute lung injury.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease involving oxidative stress as well as a wide variety of cells activated from smoking cigarettes. There have been disappointingly few therapeutic advances in drug therapy for COPD. Plant polyphenols have been the topic of much research regarding their antioxidant activities and antiinflammatory and immunomodulatory effects. In the present study, we ask whether apple polyphenol provides protection against cigarette smoke (CS)-induced acute lung injury. METHODS: ICR mice were exposed to CS for 4 d with increasing exposure time for up to 6 h per day to elicit epithelial cells injury. One hour before smoke exposure, mice were treated with apple polyphenol (APP) by gavage; all examinations were performed 18 h after the last CS exposure. RESULTS: APP at 30, 100, or 300 mg not only significantly dose-dependently reduced the CS-induced accumulation of inflammatory cells and gene/protein expression of proinflammatory factors both in the lung and in bronchoalveolar lavage fluid, but also significantly reversed oxidative stress in the lungs. Additionally, treatment with APP also significantly regulated the CS-induced imbalance of matrix metalloproteinases-9/tissue inhibitor of metalloproteinase-1 expression in the lungs. To investigate further the possible signaling pathway of APP effects, we examined protein expression of p-P38 MAPK by immunohistochemistry that found treatment with APP significantly decreased the CS-induced increases of p-P38 expression in the lungs. CONCLUSION: Taken together, APP may be a potential dietary nutrient supplement agent to improve quality of life of COPD patients by inhibiting CS-exposed acute lung injury via P38 MAPK signaling pathway.

RNAi-mediated inhibition of presenilin 2 inhibits glioma cell growth and invasion and is involved in the regulation of Nrg1/ErbB signaling.

Gliomas are the leading cause of death among adults with primary brain malignancies. Treatment for malignant gliomas remains limited, and targeted therapies have been incompletely explored. In this study, we found that the protein expression of presenilin 2 (PS2) was significantly increased in glioma tissues, at least partially because of promoter demethylation. We further evaluated the biological functions of PS2 in U251 glioma cell proliferation, migration, invasion, and tumor growth in vivo by specific inhibition of PS2 using short hairpin RNA (shRNA). We found that PS2 depletion inhibited glioma cell growth as the result of inhibited proliferation and induced apoptosis. PS2 depletion also decreased the invasive capability of glioma cells and anchorage-independent colony formation in soft agar. Moreover, suppression of PS2 expression significantly impaired the growth of glioma xenografts in nude mice. Finally, the decrease in glioma cell growth caused by PS2 depletion seems to involve Nrg1/ErbB signaling. In summary, our data highlight the use of RNA interference (RNAi) as a tool to better understand the molecular basis of PS2 in glioma progression and to uncover new targets for the treatment of glioma.

Nuclear translocation of MRP1 contributes to multidrug resistance of mucoepidermoid carcinoma.

Multidrug resistance-related protein 1 (MRP1 or ABCC1), a membrane-bound energy-dependent efflux transporter, is overexpressed in several kinds of multidrug-resistant cell lines and related to multidrug-resistance (MDR) of various cancers. In this study, we investigated whether MRP1 was involved in the chemoresistance of mucoepidermoid carcinoma (MEC). We demonstrated that down-regulation of MRP1 in MC3/5FU, a drug-resistant MEC cell line, by RNA interference increased the drug sensitivity of the cells to 5-fluorouracil, doxorubicin, pharmorubicin, bleomycin-A5, cis-platinum and taxol. However, no significant quantitative difference of MRP1 mRNA and protein expression was found between MC3/5FU cells and its parental cell line (MC3) as determined by RT-PCR and Western blot. Interestingly, MRP1 was translocated from the cytoplasmic membrane of the MC3 cells to the nuclei of MC3/5FU cells as revealed by indirect immunofluorescence staining. Furthermore, MRP1 down-regulation mainly decreased the nuclear expression of MRP1 rather than the cytoplasmic membrane expression. Our results suggested that MRP1 was involved in the chemoresistance of MEC and MRP1 may confer drug-resistance by a mechanism associated with its nuclear translocation.