Stratification of Lung Adenocarcinoma Patients Based on In Silico and Immunohistochemistry Analyses of Oxidative Stress-Related Genes.

Background: Lung adenocarcinoma (LUAD) remains heterogeneous in the prognosis of patients; oxidative stress (OS) has been widely linked to cancer progression. Therefore, it is necessary to explore the prognostic value of the OS-associated genes in LUAD. Methods: An OS-associated prognostic signature was developed using the Cox regression and random forest model in The Cancer Genome Atlas-LUAD dataset. Kaplan-Meier (K-M) survival curve and time-dependent receiver operating characteristic (tROC) curves were applied to evaluate and validate the predictive accuracy of this signature among the training and testing cohorts. A nomogram was constructed and also verified by the concordance index (C-index), calibration curves, and tROC curves, respectively. ESTIMATE algorithm and CIBERSORT algorithms were conducted to explore the signature's immune characteristics. Core target genes of the prognostic signature were identified in the protein-protein interaction network. Results: A six OS-associated prognostic gene signature (CDC25C, ERO1A, GRIA1, TERT, CAV1, BDNF) was developed. The tROC and K-M survival curves in the training and testing cohorts revealed that the signature had good and robust predictive capability to predict the overall survival of LUAD patients. Meanwhile, the risk score was an independent prognostic factor influencing patients' overall survival. The results of the C-index (0.714), calibration curves, and the 1-, 2-, and 3-year tROC curves (area under the curve = 0.703, 0.737, and 0.723, respectively) suggested that the nomogram had good predictive efficacy and prognostic value for LUAD. Then, the authors found that the high-risk group may be depletion or loss of antitumor function of immune cells. Finally, 10 core genes of the signature were predicted. Conclusion: Their study may provide a novel understanding for the identification of prognostic stratification in LUAD patients, as well as the regulation of OS-associated genes in LUAD progression.

Cystic Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies.

A common life-threatening hereditary disease, Cystic Fibrosis (CF), affects primarily Caucasian infants. High sweat-salt levels are observed as a result of a single autosomal mutation in chromosome 7 that affects the critical function of the cystic fibrosis transmembrane regulator (CFTR). For establishing tailored treatment strategies, it is important to understand the broad range of CFTR mutations and their impacts on disease pathophysiology. This study thoroughly investigates the six main classes of classification of CFTR mutations based on their functional effects. Each class is distinguished by distinct molecular flaws, such as poor protein synthesis, misfolding, gating defects, conduction defects, and decreased CFTR expression at the apical membrane. Furthermore, this paper focuses on the emerging field of CFTR modulators, which intend to restore CFTR function or mitigate its consequences. These modulators, which are characterized by the mode of action and targeted mutation class, have the potential to provide personalized therapy regimens in CF patients. This review provides valuable insights into the genetic basis of CF pathology, and highlights the potential for precision medicine methods in CF therapy by thoroughly investigating CFTR mutation classification and related modulators.

Serum metabolite profiling reveals metabolic characteristics of sepsis patients using LC/MS-based metabolic profiles: a cross-sectional study.

BACKGROUND: Individuals with sepsis exhibited a higher likelihood of benefiting from early initiation of specialized treatment to enhance the prognosis of the condition. The objective of this study is to identify potential biomarkers of sepsis by means of serum metabolomics. MATERIALS AND METHODS: The screening of putative biomarkers of sepsis was conducted using serum samples from patients with sepsis and a control group of healthy individuals. The pathogenesis of sepsis was determined through the utilization of liquid chromatography-mass spectrometry-based metabolic profiles and bioinformatic techniques, which in turn provided a foundation for timely diagnosis and intervention. RESULTS: Individuals with sepsis had significantly different metabolic characteristics compared to those with normal health. The concentrations of phosphatidylcholines (PCs), phosphatidylserine (PS), lysophosphatidylethanolamine (LysoPEs), and lysophosphatidylcholine (LysoPCs) exhibited a decrease, while the levels of creatinine, C17-Sphinganine, and PS(22:0/22:1(11Z)) demonstrated an increase in the serum of sepsis patients when compared to the control group. Additionally, ROC curves were generated to assess the discriminatory ability of the differentially expressed metabolites. The area under the ROC curve for PS (22:0/22:1(11Z)) and C17-Sphinganine were determined to be 0.976 and 0.913, respectively. These metabolites may potentially serve as diagnostic markers for sepsis. Additionally, the pathogenesis of sepsis is associated with mTOR signaling, NF-κB signaling pathway, calcium signaling, calcium transport, and tRNA charging pathway. CONCLUSION: The identification of differential expression of these metabolites in sepsis serum samples could aid in the timely diagnosis and intervention of sepsis, as well as enhance our understanding of its pathogenesis.

Effect of ticagrelor on the serum level of hs-CRP, ESM-1 and short-term prognosis of patients with acute STEMI.

The aim of the present study was to observe and investigate the changes in the serum level of high-sensitivity C-reactive protein (hs-CRP), the endothelial cell-specific molecule-1 (ESM-1) and short-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated by ticagrelor. We enrolled 107 patients with acute STEMI who were admitted in the Department of Cardiology for the first time with occurrence of symptoms, and we successfully performed emergency operation of percutaneous coronary intervention. The patients were divided into two groups, 54 patients in the ticagrelor group (treatment group) and 53 patients in the clopidogrel group (control group), according to the administration of ticagrelor or clopidogrel in dual anti-platelet therapy. Then, we observed the changes at the time of admission, at 24 h, and 4th and 7th day after administration and investigated the correlations between them and the effect of ticagrelor on the short-term prognosis of acute STEMI patients. Significant increases of the serum levels of hs-CRP and ESM-1 were seen in patients of the two groups 24 h after administration of drugs with statistically significant differences between the groups (P<0.05), and on the 4th and 7th day we found a downward trend with statistically significant differences (P<0.05). The level of ESM-1 enhanced the increase of hs-CRP, indicating there was a positive correlation between ESM-1 and hs-CRP (r=0.535, P<0.001). A comparison of the occurrence rates of ischemic outcome event, bleeding and overall adverse events between the two groups yielded no statistically significant difference (P>0.05). In conclusion, the present study demonstrates that ticagrelor can reduce the prevalence of inflammatory reactions rapidly and stabilize the functions of vascular endothelium to improve the stability of atherosclerosis plaque and decrease the occurrence rate of thrombosis as well as ischemic outcome event without any obvious increase in the risk of bleeding. Thus, ticagrelor should be recommended in clinical practices for the treatment of patients with STEMI.

Analysis of Serum Endothelial Cell-Specific Molecule 1 (Endocan) Level in Type 2 Diabetes Mellitus With Acute ST-Segment Elevation Myocardial Infarction and its Correlation: A Pilot Study.

Endothelial cell-specific molecule 1 (ESM-1; endocan) is expressed by endothelial cells, and it can be overexpressed in diabetic patients. However, little is known concerning diabetic patients with acute ST-segment elevation myocardial infarction (STEMI). Therefore, we assessed serum ESM-1 level in patients having type 2 diabetes mellitus (T2DM) STEMI; 72 patients with DM (38 with and 34 without vascular disease) and 33 individuals as a control group were included. There was a significant difference in serum ESM-1 level between the T2DM group and the control group (P = .03). There was also a significant difference in serum ESM-1 level between the T2DM with STEMI group and newly diagnosed T2DM group without vascular disease (P = .01). In patients with T2DM, serum ESM-1 levels correlated positively with high-sensitivity C-reactive protein levels and the neutrophil to lymphocyte ratio (r = .321, P = .006 and r = .320, P = .006). Our findings suggest that serum ESM-1 level may be a novel endothelial dysfunction biomarker and it may be related to vascular disease in T2DM.

Serum Endothelial Cell-Specific Molecule 1 (Endocan) Levels in Patients With Acute Myocardial Infarction and Its Clinical Significance.

Endothelial dysfunction is involved in the process of acute myocardial infarction (AMI), that is, the endothelial cell-specific molecule 1 (ESM-1; endocan) is a novel endothelial dysfunction marker. However, the relationship between patients with AMI and serum ESM-1 levels is not very clear. Patients with AMI (n = 216) and a control group (n = 60) without AMI were included in the study. High-sensitivity C-reactive protein (hsCRP) was measured, and the severity of AMI was assessed by a modified Gensini stenosis scoring system. Serum ESM-1 levels were significantly higher in the AMI group ( P < .05). High-sensitivity C-reactive protein levels were also significantly higher in the AMI group ( P < .05). In patients with AMI, serum ESM-1 levels were not significantly correlated with hsCRP levels. There was no significant correlation between serum ESM-1 level and Gensini score. Our findings suggest that serum ESM-1 levels may be a novel biomarker of endothelial dysfunction in patients with AMI.

Efficacy of Laparoscopic Primary Repair in the Treatment of Colonic Perforation After Colonoscopy: A Review of 40,127 Patients.

BACKGROUND: In recent years, increasing colonoscopy use increases the incidence of colonic perforation. Colonic perforation during colonoscopy is a rare but extremely serious complication. Traditionally, the management of colonic perforation is explorative laparotomy with bowel resection. Treatment using laparoscopic approach is a novel approach, and has been reported in some recent literatures. Nowadays, the using of laparoscopic primary repair in treatment of colonoscopic perforations has not been confirmed. This study retrospectively reviewed our experiences in treating colonoscopic perforations by laparoscopic primary repair. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the laparoscopic primary repair in the treatment of colonic perforations during colonoscopy. METHODS: Between January 2003 and December 2014, data were collected retrospectively on all patients who underwent colonoscopy and compared the recovery parameters and morbidity of patients who underwent laparoscopic primary repair versus those who had open surgery. RESULTS: A total of 40,127 colonoscopies were performed during the study period. There were 24 patients who underwent primary repair [13 underwent laparoscopic surgery (LS) and 8 underwent open surgery (OS)]. There were no demographic differences between the LS and OS groups (P>0.05). Compared with OS group, patients who underwent laparoscopic repair had a significantly shorter incision length (LS: 3.15±0.35 mm vs. OS: 12.60±2.87 mm, P=0.000), fewer blood loss (LS: 28.54±10.82 mL vs. OS: 159.25±46.90 mL, P=0.000), shorter postoperative hospital stay (LS: 8.31±1.93 d vs. OS: 12.38±1.41 d, P=0.000), and shorter postoperative fasting time (LS: 3.38±0.7 d vs. OS: 5.25±0.71 d, P=0.000). The operative time of LS group was a little longer than OS group, but there were no significant differences (LS: 86.31±22.22 min vs. OS: 75.125 ±14.24 min, P=NS). CONCLUSIONS: Laparoscopic primary repair is safe and effective in resolving colonic perforation due to colonoscopy, and it might offer benefits over the open approach.

Relationship of Endothelial Cell-Specific Molecule 1 Level in Stress Hyperglycemia Patients With Acute ST-Segment Elevation Myocardial Infarction: A Pilot Study.

Endothelial cell-specific molecule 1 ([ESM-1], endocan) is a new biomarker of endothelial dysfunction, which may be involved in the pathogenesis of atherosclerosis and stress hyperglycemia in patients with acute ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated serum ESM-1 levels in patients with stress hyperglycemia having STEMI; 105 patients with STEMI and 33 individuals as a control group were included in the study. The patients were followed up for 3 months and major adverse cardiac events (MACEs) were recorded. Serum ESM-1 level was significantly higher in patients with stress hyperglycemia patients having STEMI (P < .05). In these patients, serum ESM-1 levels correlated positively with glucose levels (r = .21, P < .05). Multiple factor logistic regression analysis showed that serum ESM-1 levels >1.01 ng/mL (odds ratio 3.01, 95% confidence interval 1.05-8.64, P < .05) were an independent predictor of MACEs. Our findings suggest that ESM-1 is a novel biomarker overexpressed in patients with stress hyperglycemia having STEMI, admission glucose levels are associated with ESM-1 levels, and ESM-1 is an independent predictor of MACEs. An ESM-1 level >1.01 ng/mL is likely to predict a greater risk of MACEs.