LncRNA FEZF1-AS1 facilitates cisplatin resistance in non-small cell lung cancer through modulating the miR-32-5p-glutaminase axis.

Non-small cell lung cancer (NSCLC) is one of the prevalent malignancies. Cisplatin (CDDP) is a conventional chemotherapeutic agent against NSCLC. However, inherent and acquired chemoresistance limited the effectiveness of cisplatin in treatment of NSCLC. This study aimed to investigate the roles and underlying mechanisms of lncRNA-FEZF1-AS1 in mediating cisplatin sensitivity in NSCLC. We found that FEZF1-AS1 levels were significantly higher in lung cancer patients and cell lines. Blocking FEZF1-AS1 sensitized lung cancer cells to cisplatin. Additionally, both glutamine metabolism and FEZF1-AS1 were significantly elevated in cisplatin resistant NSCLC cell lines, A549/CDDP R and SK-MES-1 CDDP/R. Analysis using bioinformatics, RNA pull-down assay and luciferase assay demonstrated that FEZF1-AS1 sponged miR-32-5p, which acted as a tumor suppressor in NSCLC. Glutaminase (GLS), a key enzyme in the glutamine metabolism, was predicted and validated as the direct target of miR-32-5p in NSCLC cells. Inhibiting glutamine metabolism or reducing glutamine supply effectively resensitized cisplatin-resistant cells. Furthermore, restoring miR-32-5p in FEZF1-AS1-overexpressing cisplatin resistant cells successfully overcame FEZF1-AS1-mediated cisplatin resistance by targeting GLS. These findings were further supported by in vivo xenograft mice experiments. This study uncovered the roles and molecular mechanisms of lncRNA FEZF1-AS1 in mediating cisplatin resistance in NSCLC, specifically through modulating the miR-32-5p-GLS axis, providing support for the development of new therapeutic approaches against chemoresistant lung cancer.

Change of Left Ventricular Geometric Pattern in Patients with Preserved Ejection Fraction Undergoing Coronary Artery Bypass Grafting.

Left ventricular (LV) remodeling and geometric patterns are associated with variations in prognosis. Two hundred twenty-eight patients who underwent selective isolated coronary artery bypass grafting (CABG) were included, divided into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy at baseline. More than half participants with normal geometry at baseline remained in that category, and similar ratio of concentric remodeling reverted to normal geometry on follow-up. The concentric hypertrophy at baseline tended to progress to eccentric geometry rather than normal geometry, while changes from eccentric to concentric hypertrophy was uncommon. iLVEDD had a significant association with an increased risk of developing an abnormal geometric pattern from a normal or concentric remodeling pattern, and iLVESD and LAScd involved in the regression from an abnormal geometric pattern. Thus, dynamic changes in LV geometric pattern are common on 1-year follow-up after CABG and LA strain has an incremental role for early detection in this process.

Changes and predictors of secondary mild mitral regurgitation after coronary artery bypass grafting.

BACKGROUND: Secondary mitral regurgitation (SMR) has been related to left ventricular (LV) remodeling and geometric deformation of the mitral apparatus after myocardial infarction (MI), and proved to be associated with adverse cardiac events. We assessed the proportion of mild SMR before and after isolated coronary artery bypass grafting (CABG) surgery, and further study to evaluate dynamic changes of MR and the determinants of such process on 1 year follow-up. METHODS: From 2019 to 2021, cohort study of 171 consecutive hospitalized patients who underwent selective isolated CABG surgery were included and divided into the control group and mild MR group according to whether mild MR occurred at baseline. Univariate analysis and multivariate logistic regression analysis were used to test the associations of changes in MR after CABG, and p < 0.05 was considered significant. RESULTS: The mean age of the cohort was 61.31 ± 8.71 years and 78.95% were male at baseline, divided into the control group (74.85%) and mild MR group (25.15%), respectively. The LV volumetric and size parameters were higher in the mild MR group, with decline in LV and left atrial (LA) strain measurements. About half participants with mild MR at baseline persisted in that category and the rest reverted to none MR on follow-up, while preoperative left main coronary artery occlusion may impede the improvement (p < 0.05). The control group at baseline tended to maintain none MR and one-eighth progressed to mild MR on follow-up, moreover older age and lower LVEF emerged as key correlation of this development. LA volume index (LAVi) was associated with an increased risk of developing mild MR (p < 0.05). CONCLUSIONS: Patients with secondary mild MR had LA dysfunction and CABG surgery promoted regression of MR. LAV has an incremental role for early detection of change in MR over time after surgery.

Strengthening effects of bone marrow mononuclear cells with intensive atorvastatin in acute myocardial infarction.

OBJECTIVE: To test whether intensive atorvastatin (ATV) increases the efficacy of transplantation with autologous bone marrow mononuclear cells (MNCs) in patients suffering from anterior ST-elevated myocardial infarction (STEMI). METHODS: This clinical trial was under a 2×2 factorial design, enrolling 100 STEMI patients, randomly into four groups of regular (RA) or intensive ATV (IA) with MNCs or placebo. The primary endpoint was the change of left ventricular ejection fraction (LVEF) at 1-year follow-up from baseline, primarily assessed by MRI. The secondary endpoints included other parameters of cardiac function, remodelling and regeneration determined by MRI, echocardiography, positron emission tomography (PET) and biomarkers. RESULTS: All the STEMI patients with transplantation of MNCs showed significantly increased LVEF change values than those with placebo (p=0.01) with only in the IA+MNCs patients group demonstrating significantly elevation of LVEF than in the IA+placebo group (+12.6% (95%CI 10.4 to 19.3) vs +5.0% (95%CI 4.0 to 10.0), p=0.001), pointing to a better synergy between ATV and MNCs (p=0.019). PET analysis revealed significantly increased viable areas of myocardium (p=0.015), while the scar sizes (p=0.026) and blood aminoterminal pro-B-type natriuretic peptide (p<0.034) reduced. All these above benefits of MNCs were also attributed to IA+MNCs instead of RA+MNCs group of patients with STEMI. CONCLUSIONS: Intensive ATV treatment augments the therapeutic efficacy of MNCs in patients with anterior STEMI at the convalescent stage. The treatment with the protocol of intensive ATV and MNC combination offers a clinically essential approach for myocardial infarction. TRIAL REGISTRATION NUMBER: NCT00979758.

Transplantation efficacy of autologous bone marrow mesenchymal stem cells combined with atorvastatin for acute myocardial infarction (TEAM-AMI): rationale and design of a randomized, double-blind, placebo-controlled, multi-center, Phase II TEAM-AMI trial.

Aim: To determine the efficacy and safety of intracoronary infusion of autologous bone marrow mesenchymal stem cells (MSCINJ) in combination with intensive atorvastatin (ATV) treatment for patients with anterior ST-segment elevation myocardial infarction-elevation myocardial infarction. Patients & methods: The trial enrolls a total of 100 patients with anterior ST-elevation myocardial infarction. The subjects are randomly assigned (1:1:1:1) to receive routine ATV (20 mg/d) with placebo or MSCsINJ and intensive ATV (80 mg/d) with placebo or MSCsINJ. The primary end point is the absolute change of left ventricular ejection fraction within 12 months. The secondary end points include parameters in cardiac function, remodeling and regeneration, quality of life, biomarkers and clinical outcomes. Results & conclusion: The trial will implicate the essential of cardiac micro-environment improvement ('fertilizing') for cell-based therapy. Clinical Trial Registration: NCT03047772.

Two-dimensional speckle tracking echocardiography assessed right ventricular function and exercise capacity in pre-capillary pulmonary hypertension.

Resting two-dimensional speckle tracking echocardiography (2D-STE) identified right ventricular (RV) systolic function were reported to predict exercise capacity in pulmonary hypertension (PH) patients, but little attention had been payed to 2D-STE detected RV diastolic function. Therefore, we aim to elucidate and compare the relations between 2D-STE identified RV diastolic/systolic functions and peak oxygen consumption (PVO2) determined by cardiopulmonary exercise testing (CPET) in pre-capillary PH. 2D-STE was performed in 66 pre-capillary PH patients and 28 healthy controls. Linear correlation and multivariate regression analyses were performed to evaluate and compare the relations between RV 2D-STE parameters and PVO2. Receiver operating characteristic curves were used to compare the predictive value of 2D-STE parameters in predicting the cut-off-PVO2 < 11 ml/min/kg. There were significant differences of all the 2D-STE parameters between PH patients and healthy controls. In patients, RV-peak global longitudinal strain (GLS, rs = - 0.498, P < 0.001), RV- peak systolic strain rate (GSRs, rs = - 0.537, P < 0.001) and RV- peak early diastolic strain rate (GSRe, rs = 0.527, P < 0.001) significantly correlated with PVO2, but no significant correlation was observed between RV- peak late diastolic strain rate (GSRa, rs = 0.208, P = 0.093) and PVO2. The first multivariate regression analysis of clinical data without echocardiographic parameters identified WHO functional class, NT-proBNP and BMI as independent predictors of PVO2 (Model-1, adjusted r2 = 0.421, P < 0.001); Then we added conventional echocardiographic parameters and 2D-STE parameters to the clinical data, identified S,(Model-2,adjusted r2 = 0.502, P < 0.001), RV-GLS (Model-3, adjusted r2 = 0.491, P < 0.001), RV-GSRe (Model-4, adjusted r2 = 0.500, P < 0.001) and RV-GSRs (Model-5, adjusted r2 = 0.519, P < 0.001) as independent predictors of PVO2, respectively. The predictive power was increased, and Model-5 including RV-GSRs showed the highest predictive capability. ROC curves found RV-GSRs expressed the strongest predictive value (AUC = 0.88, P < 0.001), and RV-GSRs > - 0.65/s had a 88.2% sensibility and 82.2% specificity to predict PVO2 < 11 ml/min/kg. 2D-STE assessed RV function improves the prediction of exercise capacity represented by PVO2 in pre-capillary PH.

Clinical risk factors of prediabetes in Taiwanese women without substance uses (tobacco, alcohol, or areca nut).

BACKGROUND/PURPOSE: Individuals with prediabetes (100-125 mg/dL) and diabetes mellitus (DM) increase the risk of all-cause and cardiovascular disease (CVD) mortality. Since personal substance use such as cigarette smoking, alcohol drinking, and areca nut chewing may confound the true effect of clinical biochemistries on the risk of prediabetes, this study aims to examine the relationship between clinical biochemical parameters and the risk of prediabetes among Taiwanese without the habits of consuming tobacco, alcohol drinking, or areca nut. METHODS: Women aged between 40 years and 64 years who came to one community teaching hospital between January 1, 2001 and December 31, 2008 for general health screening for the first time were studied. The general health screening is provided every 3 years gratis. The package of this health screening includes personal history, physical examination, and biochemical tests in serum and urine. RESULTS: In total, 8580 nonsmoking, nondrinking, and nonareca nut chewing women who did not have a history of DM were eligible for this study. Of these, 1861 (21.7%) out of 8580 women were prediabetic. Compared to women with normal fasting glucose (NFG), we found a dose-response relationship of the risk of prediabetes with age and body mass index (BMI) and total cholesterol, triglyceride, glutamic-pyruvic transaminase (GPT), and uric acid in serum. Women with hypertension or proteinuria (≥30 mg/dL) had also an increased risk to have prediabetes. CONCLUSION: Besides age, the factors of BMI, hypertension, dyslipidemia, GPT, hyperuricemia, and proteinuria are the main risk factors for prediabetes in Taiwanese women without substance uses. A follow-up study is necessary to clarify the causality of these important biochemical parameters and prediabetes.

Clinical analysis of acute lung injury after esophagectomy.

OBJECTIVE: Acute lung injury (ALI) is one of the most severe postoperative complications after esophagectomy for esophageal cancer patients. In order to clarify the mechanism of ALI, we, therefore, studied the operative course of a group of patients who underwent elective esophagectomy. MATERIALS AND METHODS: We retrospectively analyzed 75 patients underwent an esophagectomy and reconstruction for thoracic esophageal cancer. RESULTS: No statistically significant differences were observed between the two groups regarding their clinical backgrounds, such as their age, smoking index, preoperative pulmonary function, the location of the main tumor, and the tumor nodes metastasis stage. Operative time is thus considered to be a significant factor. The odds ratio (OR) of ALI in cases whose preoperative pulmonary function was 6.70 in comparison to the abnormal preoperative pulmonary functions. The OR for more intraoperative bleeding (>1000 g) was 0.83, compared with a lesser intraoperative bleeding although the difference was not statistically significant (P = 0.076). Anastomotic leakage occurred in four patients (44%) in Group I while it only occurred in two patient (6%) among the 33 Group II patients (P = 0.011). CONCLUSION: Greater surgical stress, such as a longer operative time, is thus considered to be associated with the first attack of ALI. The adverse events developing in the extrathoracic site, such as necrosis and local infection around anastomosis may, therefore, be the second attack. Furthermore, ALI may cause not only systemic inflammatory response syndrome but also other complications such as anastomotic leakage.

Bereaved females are more likely to suffer from mood problems even if they do not meet the criteria for prolonged grief.

PURPOSE: The goal of this study was to describe the gender difference of grief experience and mood distress among caregivers who cared for terminal cancer patients residing in a hospice ward. METHODS: This study recruited 432 caregivers who cared for terminal cancer patients in the hospice ward. Caregivers received telephone interviews 6 months after the patients had died. The Chinese versions of the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Inventory of Complicated Grief (ICG) developed in 1995 by Prigerson et al. were employed to assess the mood distress and grief status. RESULTS: Total scores of BDI, BAI, and ICG were significantly higher in females. Six out of twenty-one items of BDI, lack of satisfaction, crying spells, sleep disturbance, fatigability, somatic preoccupation, and loss of libido, showed significantly higher scores in females. According to BAI, inability to relax, dizziness, fear of dying, fright, flushed face, and hot/cold sweats were significantly higher in females. After adjustment for potential confounders, the results show that female gender is associated with higher BDI (regression coefficient 3.24, 95% CI: 1.48-4.99), BAI (3.8; 1.11-6.50), and ICG (4.25, 1.09-7.40). Dichotomizing the BDI, BAI, and ICG into severe and nonsevere cases, the results showed that gender only contributes to severe anxiety status (BAI ≥ 36), but not to severe depression (BDI ≥ 29) or to prolonged grief (ICG ≥ 25). CONCLUSIONS: Bereaved females had higher scores for depression and anxiety than males. Female gender is associated with severe anxiety; however, it is not associated with severe depression or prolonged grief.