Lipopolysaccharide (LPS) can activate alveolar epithelial cells (AECs) and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in ...the activation of NF-κB. NF-κB is a key intercellular signaling event that mediates cell inflammatory responses. The aim of the study is to investigate in an in vitro model the inflammatory responses of AECs induced by LPS and the probable mechanism underlined the observed inflammatory responses. So cytokines of ICAM-1, TNF-α and IL-8 secreted by LPS-activated AECs were observed. And the initial signal molecule (the expression of TLR-4 mRNA) and the key intracellular steps (the activation of NF-κB) were studied in detail.
The study was performed on A549 cells (Human lung adenocarcinoma cell line). A549 cells were divided into two groups: control, and LPS interference group. Proinflammatory cytokines ICAM-1, TNF-α and IL-8 were detected by ELISA or radioimmunological methods. The expression of TLR-4 mRNA was detec
This study aimed to construct an m6A-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using data obtained from The ...Cancer Genome Atlas (TCGA) database.
The KIRC patient data were downloaded from TCGA database and m6A-related genes were obtained from published articles. Pearson correlation analysis was implemented to identify m6A-related lncRNAs. Univariate, Lasso, and multivariate Cox regression analyses were used to identifying prognostic risk-associated lncRNAs. Five lncRNAs were identified and used to construct a prognostic signature in training set. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were applied to evaluate reliability and sensitivity of the signature in testing set and overall set, respectively. A prognostic nomogram was established to predict the probable 1-, 3-, and 5-year overall survival of KIRC patients quantitatively. GSEA was performed to explore the potential biological processes and cellular pathways. Besides, the lncRNA/miRNA/mRNA ceRNA network and PPI network were constructed based on weighted gene co-expression network analysis (WGCNA). Functional Enrichment Analysis was used to identify the biological functions of m6A-related lncRNAs.
We constructed and verified an m6A-related lncRNAs prognostic signature of KIRC patients in TCGA database. We confirmed that the survival rates of KIRC patients with high-risk subgroup were significantly poorer than those with low-risk subgroup in the training set and testing set. ROC curves indicated that the prognostic signature had a reliable predictive capability in the training set (AUC = 0.802) and testing set (AUC = 0.725), respectively. Also, we established a prognostic nomogram with a high C-index and accomplished good prediction accuracy. The lncRNA/miRNA/mRNA ceRNA network and PPI network, as well as functional enrichment analysis provided us with new ways to search for potential biological functions.
We constructed an m6A-related lncRNAs prognostic signature which could accurately predict the prognosis of KIRC patients.
AIM：To compare the endomicroscopic image quality of integrated confocal laser endomicroscopy（iCLE）and sedation efficacy of propofolvs midazolam plus fentanyl（M/F）.METHODS：Consecutive outpatients ...undergoing iCLE were prospectively recruited and randomized to the propofol group（P group）or M/F group.The patient,performing endoscopist and endoscopic assistant were blinded to the randomization.The quality of endomicro-scopic images and anesthetic efficacy outcomes were blindly evaluated after iCLE examination.RESULTS：There were significantly more good quality endomicroscopic images in the propofol group than in the M/F group（72.75%vs 52.89%,P0.001）.The diagnostic accuracy for upper gastrointestinal mucosal lesions using confocal laser endomicroscopy favors the P group,although this did not reach statistical significance.Adverse events and patient assessment were not significantly different for M/F vs propofol except for more frequent intraprocedural recall with M/F.Procedure duration and sedation times were significantly longer in the M/F group,while the scores of endoscopist,anesthetist and assistant assessment were all significantly better in the P group.CONCLUSION：Sedation with propofol might increase the proportion of good quality endomicroscopic images,and may result in improved procedural efficacy and diagnostic accuracy during iCLE examination.
The study aimed to identify an autophagy-related molecular subtype and characterize a novel defined autophagy-immune related genes score (AI-score) signature and prognosis model in bladder cancer ...(BLCA) patients using public databases.
The transcriptome cohorts downloaded from TCGA and GEO database were carried out with genomic analysis and unsupervised methods to obtain autophagy-related molecular subtypes. The single-sample gene-set enrichment analysis (ssGSEA) was utilized to perform immune subtype clustering. We defined a novel autophagy subtype and evaluated the role in TME cell infiltration. Then, the principal-component analysis (PCA) was applied to construct an AI-score signature. Subsequently, two immunotherapeutic cohorts were used to evaluate the predictive value in immunotherapeutic benefits and immune response. Finally, univariate, Lasso and multivariate Cox regression algorithm were used to construct and evaluate an autophagy-immune-related genes prognosis model. Also, qRT-PCR and IHC was applied to validate the expression of the 6 genes in the model.
Three distinct autophagy clusters and immune-related clusters were identified, and a novel autophagy-related molecular subtypes were defined. Furthermore, the roles in TME cell infiltration and clinical traits for the autophagy subtypes were characterized. Meanwhile, we constructed an AI-score signature and demonstrated it could predict genetic mutation, clinicopathological traits, prognosis, and TME stromal activity. We found that it could accurately predict the clinicopathological characteristics and immune response of individual BLCA patients and provide guidance for selecting immunotherapy. Ultimately, we constructed and verified an autophagy-immune-related prognostic model of BLCA patients and established a prognostic nomogram with a good prediction accuracy.
We constructed AI-score signatures and prognosis risk model to characterize their role in clinical features and TME immune cell infiltration. It revealed that the AI-score signature and prognosis model could be a valid predictive tool, which could accurately predict the prognosis of BLCA patients and contribute to choosing effective personalized immunotherapy strategies.
Background： Atherosclerosis （AS） is an inflammatory disease. Inflammation was considered to play a role in the whole process of AS. This study aimed to analyze the relationships of inflammatory ...factors and risk factors with different target organ damages （TOD） in essential hypertension （EH） patients and to explore its clinical significance. Methods： A total of 294 EH patients were selected and divided into four groups according to their conditions of TOD. Forty-eight healthy subjects were selected as control. The clinical biochemical parameters, serum amyloid A, serum tryptase, and lipoprotein-associated phospholipase A2 （Lp-PLA2） in each group were detected, and the related risk factors were also statistically analyzed. Results： Fihrinogen （Fbg） was the most significant independent risk factor in acute coronary syndrome （ACS） group （odds ratio OR： 22.242, 95% confidence interval CI： 6.458-76.609, P 〈 0.001） with the largest absolute value of the standardized partial regression coefficient B＇ （b＇： 1.079）. Lp-PLA2 was the most significant independent risk factor in stroke group （OR： 13.699, 95% CI： 5.236-35.837, P 〈 0.001） with b＂ 0.708. Uric acid （UA） was the most significant independent risk factor in renal damage group （OR： 15.307, 95% CI：4.022 58.250, P〈0.001）with b＇= 1.026. Conclusions： Fbg, Lp-PLA2, and UA are the strongest independent risk factors toward the occurrence of ACS, ischemic stroke, and renal damage in EH patients, thus exhibiting the greatest impacts on the occurrence ofACS, ischemic stroke, and renal damage in EH patients, respectively.
Background The relationship between inflammatory markers and the characteristics of coronary atherosclerosis plaques is uncertain. The aim of the present study was to evaluate the relationship ...between the characteristics of coronary atherosclerosis plaques and inflammatory markers such as high sensitivity C-reactive proteins （Hs-CRP） and interleukin-6 （IL-6）. Methods All patients suspected of having coronary heart disease （CHD） underwent Siemens 64-slice CT angiography （64-SCTA） to distinguish the quality of plaque of coronary artery lesions. Blood samples were taken to measure levels of serum Hs-CRP and IL-6 in different plaque groups and the control group and compared with the value of 64-SCTA for detection of coronary artery plaque. Results The sensitivity of detecting coronary artery plaque by 64-SCTA was 87.4%, the specificity was 87.1%, the positive predictive value was 82.2%, and the negative predictive value was 91.0%. Comparing the levels of serum Hs-CRP and IL-6 among plaque groups, the mean levels of serum Hs-CRP and IL-6 in three plaque groups were significantly higher than those in the control group （P 〈0.01）. The mean levels of serum Hs-CRP and IL-6 in the soft plaque group and mixed plaque group were significantly higher than those in hard plaque group （P〈0.01）. Plaque burden in the soft plaque group and mixed plaque group was significantly higher than in the hard plaque group （P 〈0.01）, but there was no statistical difference between the soft plaque group and mixed plaque group （P=-0.246）. There was a negative correlation between the CT scale and Hs-CRP and IL-6 levels in the soft plaque group （r= -0.621, P〈0.01, and r= -0.593, P 〈0.01 respectively）. There was a positive correlation between the plaque burden and Hs-CRP and IL-6 levels in the soft plaque group （r=0.579, P〈0.05 and r=0.429, P〈0.05 respectively）. Conclusions 64-SCTA is an effective way to distinguish the different quality of coronary atherosclerosis plaque. Serum Hs-CRP and IL-6 levels can be considered as the indexes to judge the degree of CHD and may reflect the activity of plaque in CHD patients. Thus it is important for clinical diagnosis and risk evaluation of acute coronary syndrome （ACS） patients.
There are approximately 240 million patients with chronic hepatitis B virus(HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or ...chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the "gold standard" for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBVinfected patients, owing to its high applicability, interlaboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBVinfected patients for clinicians.
Background Toll-like receptor-4 （TLR-4） is integrally involved in lipopolysaccharide （LPS） signaling and has a requisite role in the activation of nuclear factor-κB （NF-κB）. The exact mechanisms that ...lend perfluorocarbon （PFC） liquids a cytoprotective effect have yet to be elucidated. Therefore we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated alveolar epithelial cellls （AECs）. Methods AECs （A549 cells, human lung adenocarcinoma cell line） were divided into four groups： control, PFC, LPS and LPS ＋ PFC （coculture group） groups. Intercellular adhesion molecule-1 （ICAM-1） was detected by ELISA, tumor necrosis factor-g （TNF-a） and interleukin-8 （IL-8） were detected by radioimmunological methods. The expression of TLR-4 mRNA and protein was detected by real time PCR and Western blotting, respectively. The activation of NF-κB was detected by Western blotting （proteins of I-κBa and NF-κB p65）. Results ICAM-1, TNF-a and IL-8 were significantly increased in LPS-stimulated AECs groups. The expression of TLR-4 mRNA and protein in LPS-stimulated groups was markedly increased. Meanwhile, NF-κB was activated as indicated by the significant degradation of IKB-a and the significant release of NF-κB P65 and its subsequent translocation into the nucleus. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-a and IL-8, the expression of TLR-4 rn~NA and the activity of NF-κB. Conclusions Taken together, our results demonstrate that LPS can induce AEC-related inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect AECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway, which is indicated by the significant decrease of TLR-4 expression and NF-κB activation.
Life course epidemiology should practically illustrate how risk exposures and their dynamic changes influence the occurrence,development and prognosis of chronic diseases from early life to the ...elderly.This paper develops the lifespan risk exposure measurement instrument（LREMI）in the
Background The mortality of stroke patients is strongly affected by medical complications. However, there are limited data investigating the effect of in-hospital medical complications on the ...dependency of stroke patients worldwide. We prospectively and systematically investigated the effect of medical complications on dependency of patients at 3, 6 and 12 months after stroke using the China National Stroke Registry （CNSR）. Methods This prospective cohort study collected data of patients age 〉18 years with acute ischemic stroke in 132 clinical centers distributed across 32 provinces and four municipalities （including Hong Kong region） of China, from September 2007 to August 2008. Data on medical complications, dependency and other information were obtained from paper-based registry forms. Medical complications associated with stroke outcomes were assessed using multivariable Logistic regression. Results Of 11 560 patients with acute ischemic stroke, 1826 （15.80%） presented with in-hospital medical complications. In-hospital medical complications were independent risk factors for dependency of patients at 3 months （adjusted odds ratio （OR） 2.367, 95% confidence interval （CI） 2.021-2.771）, 6 months （adjusted OR 2.257, 95% CI 1.922-2.650）, and 12 months （adjusted OR 1.820, 95% CI 1.538-2.154） after acute ischemic stroke. Conclusion The results demonstrated that the short-term and long-term dependency of acute ischemic stroke patients is significantly associated with in-hospital medical complications in China.
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