Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment.

Background: The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI). Methods: From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index). Results: The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI. Conclusion: ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.

The atypical chemokine receptor 2 reduces T cell expansion and tertiary lymphoid tissue but does not limit autoimmune organ injury in lupus-prone B6lpr mice.

Introduction: The atypical chemokine receptor 2 (ACKR2) is a chemokine scavenger receptor, which limits inflammation and organ damage in several experimental disease models including kidney diseases. However, potential roles of ACKR2 in reducing inflammation and tissue injury in autoimmune disorders like systemic lupus erythematosus (SLE) and lupus nephritis are unknown, as well as its effects on systemic autoimmunity. Methods: To characterize functional roles of ACKR2 in SLE, genetic Ackr2 deficiency was introduced into lupus-prone C57BL/6lpr (Ackr2-/- B6lpr) mice. Results: Upon inflammatory stimulation in vitro, secreted chemokine levels increased in Ackr2 deficient tubulointerstitial tissue but not glomeruli. Moreover, Ackr2 expression was induced in kidneys and lungs of female C57BL/6lpr mice developing SLE. However, female Ackr2-/- B6lpr mice at 28 weeks of age showed similar renal functional parameters as wildtype (WT)-B6lpr mice. Consistently, assessment of activity and chronicity indices for lupus nephritis revealed comparable renal injury. Interestingly, Ackr2-/- B6lpr mice showed significantly increased renal infiltrates of CD3+ T and B cells, but not neutrophils, macrophages or dendritic cells, with T cells predominantly accumulating in the tubulointerstitial compartment of Ackr2-/- B6lpr mice. In addition, histology demonstrated significantly increased peribronchial lung infiltrates of CD3+ T cells in Ackr2-/- B6lpr mice. Despite this, protein levels of pro-inflammatory chemokines and mRNA expression of inflammatory mediators were not different in kidneys and lungs of WT- and Ackr2-/- B6lpr mice. This data suggests compensatory mechanisms for sufficient chemokine clearance in Ackr2-deficient B6lpr mice in vivo. Analysis of systemic autoimmune responses revealed comparable levels of circulating lupus-associated autoantibodies and glomerular immunoglobulin deposition in the two genotypes. Interestingly, similar to kidney and lung CD4+ T cell numbers and activation were significantly increased in spleens of Ackr2-deficient B6lpr mice. In lymph nodes of Ackr2-/- B6lpr mice abundance of activated dendritic cells decreased, but CD4+ T cell numbers were comparable to WT. Moreover, increased plasma levels of CCL2 were present in Ackr2-/- B6lpr mice, which may facilitate T cell mobilization into spleens and peripheral organs. Discussion: In summary, we show that ACKR2 prevents expansion of T cells and formation of tertiary lymphoid tissue, but is not essential to limit autoimmune tissue injury in lupus-prone B6lpr mice.

Albumin-to-alkaline phosphatase ratio as a novel prognostic indicator in patients undergoing peritoneal dialysis: a propensity score matching analysis.

Background: Though the albumin-to-alkaline phosphatase ratio (AAPR) is used as a biomarker in various diseases, little is known about its effect on outcomes after peritoneal dialysis (PD). Methods: This multicenter retrospective study comprised 357 incident PD patients stratified according to the AAPR. Propensity score matching (PSM) was performed to identify 85 patients for a well-matched comparison of all-cause and cardiovascular mortality. Using Cox regression, we performed univariate and multivariate analyses to investigate the prognostic value of the AAPR and established a Kaplan-Meier curve-predicted nomogram to estimate expected overall survival (OS). We assessed the predictive accuracy using the concordance index (c-index). Results: We found that the optimal cut-off of the AAPR to predict mortality was 0.36. In the present cohort of patients undergoing PD, a low AAPR strongly correlated with worse OS. In the multivariate analysis, the AAPR was shown to be an independent marker predicting reduced OS both before [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.08-2.60, P = 0.020] and after PSM (HR 1.96, 95% CI 1.06-3.62, P = 0.020). We also observed significant differences in OS in several subgroups, but not the group of patients with comorbidities. A nomogram was established to predict overall survival, with a c-index for prediction accuracy was 0.71 after PSM. Conclusion: AAPR has potential as an independent prognostic biomarker in patients undergoing PD.

Elevated fibrinogen to pre-albumin ratio predicts mortality in peritoneal dialysis patients.

BACKGROUND: Fibrinogen to pre-albumin ratio (FPR) is a promising predictor of mortality in various cancers. The aim of this study was to explore the prognostic value of FPR to predict mortality in peritoneal dialysis (PD) patients. METHODS: We retrospectively analyzed 324 incident PD patients form January 2011 to December 2020. Patients were stratified based on the optimal thresholds for FPR at baseline to predict overall and cardiovascular mortality during follow-up. The association of FPR and all-cause and cardiovascular mortality was evaluated by Kaplan-Meier curve and Cox regression analysis. RESULTS: All patients were divided into three groups based on the optimal cutoff value of FPR. Higher FPR levels were strongly correlated with worse overall and cardiovascular mortality in PD patients. Compared with patients in the lowest FPR tertile (<14.3), those in the highest terile (≥18.8) had multivariable-adjusted hazard ratios (95% CI confidence interval) of 3.37 (1.76-6.49) and 2.86 (1.31-6.23) for all-cause and cardiovascular mortality, respectively. Significant differences in overall survival were observed across nearly all subgroups after stratification. CONCLUSIONS: Patients with a high FPR had increased all-cause and cardiovascular mortality. FPR is a potential prognostic indicator in PD patients.

The accelerated organ senescence and proteotoxicity in thyrotoxicosis mice.

The mechanism of aging has always been the focus of research, because aging is related to disease susceptibility and seriously affects people's quality of life. The diseases also accelerate the aging process, especially the pathological changes of substantive organs, such as cardiac hypertrophy, severely shortened lifespan. So, lesions in organs are both a consequence and a cause of aging. However, the disease in a given organ is not in isolation but is a systemic problem. Our previous study found that thyrotoxicosis mice model has aging characteristics including immunosenescence, lipotoxicity, malnutrition. But all these characteristics will lead to organ senescence, therefore, this study continued to study the aging changes of important organs such as heart, liver, and kidney in thyrotoxicosis mice using tandem mass tags (TMT) proteomics method. The results showed that the excess thyroxine led to cardiac hypertrophy. In the liver, the ability to synthesize functional proteins, detoxify, and metabolism were declined. The effect on the kidney was the decreased ability of detoxify and metabolism. The main finding of the present study was that the acceleration of organ senescence by excess thyroxine was due to proteotoxicity. The shared cause of proteotoxicity in the three organs included the intensify of oxidative phosphorylation, the redundancy production of ribosomes, and the lack of splicing and ubiquitin proteasome system function. Totally, proteotoxicity was another parallel between thyrotoxicosis and aging in addition to lipotoxicity. Our research provided a convenient and appropriate animal model for exploring aging mechanism and antiaging drugs.

Predictive value of glycemic gap and stress glycemia ratio among critically ill patients with acute kidney injury: a retrospective analysis of the MIMIC-III database.

BACKGROUND AND AIMS: Acute hyperglycemia has been identified as a risk factor for acute kidney injury occurrence and mortality in various diseases. The aim of the current study was to investigate the relationship between stress-induced hyperglycemia and adverse outcomes in critically ill patients with AKI. METHODS: We extracted clinical data from Multiparameter Intelligent Monitoring in Intensive Care III version 1.4. Blood glucose and glycosylated hemoglobin during the first 24 h of ICU admission were used to calculate glycemic gap and stress hyperglycemia ratio (SHR). The outcomes included ICU mortality and need for renal replacement therapy. The association of the glycemic gap and SHR with outcomes were determined via logistic regression model and receiver-operating curves. The subgroup analysis of patients with and without diabetes was performed separately. RESULTS: Higher glycemic gap and SHR were observed in patients who had increased need of RRT, higher mortality rates and longer ICU stay. Multivariate analysis demonstrated that higher glycemic gap (OR 1.01, 95%CI 1.00-1.02, P = 0.015), as well as SHR (OR 1.32; 95%CI 1.07-1.64, P = 0.009), were independently associated with ICU mortality after adjusting for potential covariates. In subgroup analysis, the association of glycemic gap and SHR were only significant in the non-diabetic population as for the outcome of ICU mortality (OR 2.25, 95%CI 1.64-3.08, P < 0.001 and OR 1.99; 95%CI 1.46-2.72, P < 0.001, respectively). CONCLUSIONS: The glycemic gap and SHR might serve as a potential prognostic indicator of ICU mortality in critically ill patients with AKI, especially in the non-diabetic population.

The anti-aging effects of Renshen Guben on thyrotoxicosis mice: Improving immunosenescence, hypoproteinemia, lipotoxicity, and intestinal flora.

With the rapid aging of the population, the control of age-related disease susceptibility and prognosis faces greater challenges. There is an urgent need for a strategy to maintain the vitality of elderly people. In this study, the effect of Renshen Guben (RSGB) oral liquid was investigated on an accelerated aging mice model of thyrotoxicosis by conventional detection methods combined with multiomics technology. The results showed that RSGB increased the number of neutrophils and lymphocytes, enhanced the function of lymphocytes, and increased the levels of complement and antimicrobial peptides, which indicated that RSGB improved the immunity of thyrotoxicosis mice at the cellular and molecular levels. RSGB corrected malnutrition in thyrotoxicosis mice by improving anemia, hypoalbuminemia, ion transporters, and vitamin-binding proteins. RSGB significantly reduced the lipotoxicity by reducing the level of fatty acids, triglyceride, sphingolipids, and glucocorticoids, thus increasing the level of docosapentaenoic acid (DPA) and bile acids, which contributed to improve immunosenescence. The intestinal defense ability of thyrotoxicosis mice was enhanced with the increase of bile acids and lactic acid bacteria by the RSGB treatment. The plant metabolomics analysis showed that there were various active components in RSGB oral liquid and medicated serum, including terpenoids, phenolic acids, flavonoids, tannin, alkaloids, organic acids, phenolamines, amino acids, and others. They have antioxidant, immune regulation, and anti-aging effects, which was the material basis of RSGB. Totally, RSGB protected the thyrotoxicosis mice against aging by improving immunosenescence, hypoproteinemia, lipotoxicity, and the intestinal flora. It will be beneficial for improving the disease susceptibility and prognosis of the elderly.

The Aging Features of Thyrotoxicosis Mice: Malnutrition, Immunosenescence and Lipotoxicity.

The problem of aging is mainly the increase of age-related diseases, and elderly patients have longer hospitalization and worse prognosis. Poorer nutritional status and immunosenescence may be predisposing and severe factors. The mechanism of the high incidence of diseases and poor prognosis behind aging is complex. Finding suitable aging models is of great significance to find strategies to prevent aging related events. In this study, the relationship between thyrotoxicosis and aging was investigated in mice. The results of routine blood tests and flow cytometry showed that immunosenescence occurred in thyrotoxicosis mice, which was characterized by a significant decrease in neutrophils, lymphocytes, CD4+/CD8+ and CD4+IFN-γ+ lymphocytes. Biochemical examination results showed that there were hypocholesterolemia, hypolipoproteinemia, and hyperlipidemia in thyrotoxicosis mice. Serum proteomics analysis showed that the downregulation of complement and coagulation proteins was another manifestation of declined immunity. Moreover, proteomics analysis showed that many downregulated proteins were related to homeostasis, mainly transport proteins. Their downregulation led to the disturbance of osmotic pressure, ion homeostasis, vitamin utilization, lipid transport, hyaluronic acid processing, and pH maintenance. Serum metabolomics analysis provided more detailed evidence of homeostasis disturbance, especially lipid metabolism disorder, including the downregulation of cholesterol, vitamin D, bile acids, docosanoids, and the upregulation of glucocorticoids, triglycerides, sphingolipids, and free fatty acids. The upregulated lipid metabolites were related to lipotoxicity, which might be one cause of immunosenescence and many aging related syndromes. This study provides evidence for the aging model of thyrotoxicosis mice, which can be used for exploring anti-aging drugs and strategies.

The Impact of Zinc Supplementation on Critically Ill Patients With Acute Kidney Injury: A Propensity Score Matching Analysis.

Background: Zinc is an essential trace element involved in multiple metabolic processes. Acute kidney injury (AKI) is associated with low plasma zinc, but outcomes with zinc supplementation in critically ill patients with AKI remain unknown. Our objective was to investigate the effectiveness of zinc supplementation in this patient population. Methods: Critically ill patients with AKI were identified from the Medical Informative Mart for Intensive Care IV database. Prosperity score matching (PSM) was applied to match patients receiving zinc treatment to those without zinc treatment. The association between zinc sulfate use and in-hospital mortality and 30-day mortality, need for renal replacement therapy (RRT), and length of stay was determined by logistic regression and Cox proportional hazards modeling. Results: A total of 9,811 AKI patients were included in the study. PSM yielded 222 pairs of patients who received zinc treatment and those who did not. Zinc supplementation was associated with reduced in-hospital mortality (HR = 0.48 (95% CI: 0.28, 0.83) P = 0.009) and 30-day mortality (HR = 0.51 (95% CI, 0.30, 0.86) P = 0.012). In the subgroup analysis, zinc use was associated with reduced in-hospital mortality in patients with stage 1 AKI and those with sepsis. Conclusions: Zinc supplementation was associated with improved survival in critically ill patients with AKI. The supplementation was especially effective in those with stage 1 AKI and sepsis. These results need to be verified in randomized controlled trials.

Prognostic Significance of the Albumin to Fibrinogen Ratio in Peritoneal Dialysis Patients.

Background: Albumin to fibrinogen ratio (AFR) is a demonstrated predictor of mortality in various diseases. The aim of this study was to evaluate the prognostic value of AFR to predict mortality in peritoneal dialysis (PD) patients. Methods: We retrospectively analyzed 212 incident PD patients from January 2010 to December 2017 and followed them until December 2019. We used receiver operating curve (ROC) analysis to determine the optimal cut-off point for AFR at baseline to predict overall and cardiovascular mortality during the follow-up period. Kaplan-Meier curve and Cox regression analysis were applied to evaluate the association between AFR and all-cause and cardiovascular mortality. Results: The optimal threshold for AFR to predict mortality was 8.48. A low AFR was strongly correlated with worse all-cause and cardiovascular mortality in PD patients. Multivariate analysis revealed that elevated AFR was an independent marker predicting reduced all-cause and cardiovascular mortality (HR 2.41, 95% CI 1.11-5.22, P = 0.026; and HR 2.18, 95% CI 1.21-3.95, P = 0.010, respectively). Conclusions: Patients with a high AFR had reduced all-cause and cardiovascular mortality. AFR is a potential prognostic biomarker in PD patients.

Prognostic significance of albumin to alkaline phosphatase ratio in critically ill patients with acute kidney injury.

OBJECTIVE: No epidemiological evidence has investigated the effect of albumin to alkaline phosphatase ratio (AAPR) on the prognosis among critically ill patients with acute kidney injury (AKI). We aimed to explore the prognostic value of AAPR in these patients. METHODS: We extracted all clinical data from MIMIC III. ROC curve analysis was used to evaluate the discrimination of AAPR for predicting in-hospital mortality. A generalized additive model was applied to identify a nonlinear association between AAPR and in-hospital mortality. The Cox proportional hazards models were used to determine the association between AAPR and in-hospital and 30-day mortality. RESULTS: A total of 6894 eligible subjects were enrolled in this study. The relationship between AAPR and in-hospital mortality was nonlinear. Multivariate analysis demonstrated that lower AAPR (AAPR < 0.35) was an independent predictor of in-hospital and 30-day mortality after adjusting for potential confounders (HR 1.74, 95% CI 1.72-2.20, P < 0.001; HR 1.89, 95% CI 1.66-2.14, P < 0.001, respectively). CONCLUSIONS: AAPR may serve as a potential prognostic biomarker in critically ill patients with AKI and lower AAPR was associated with increased risk of in-hospital and 30-day mortality among these patients.

Prognostic value of fibrinogen to albumin ratios among critically ill patients with acute kidney injury.

Fibrinogen to albumin ratios (FAR) have shown to be a promising prognostic factor for improving the predictive accuracy in various diseases. This study explores FAR's prognostic significance in critically ill patients with acute kidney injury (AKI). All clinical data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care Database III version 1.4. All patients were divided into four groups based on FAR quartiles. The primary endpoint was in-hospital mortality. A generalized additive model was applied to explore a nonlinear association between FAR and in-hospital mortality. The Cox proportional hazards models were used to determine the association between FAR and in-hospital mortality. A total of 5001 eligible subjects were enrolled. Multivariate analysis demonstrated that higher FAR was an independent predictor of in-hospital mortality after adjusting for potential confounders (HR, 95% CI 1.23, 1.03-1.48, P = 0.025). A nonlinear relationship between FAR and in-hospital mortality was observed. FAR may serve as a potential prognostic biomarker in critically patients with AKI and higher FAR was associated with increased risk of in-hospital mortality among these patients.

Prognostic value of the albumin-globulin ratio and albumin-globulin score in patients with multiple myeloma.

OBJECTIVE: The albumin-globulin ratio (AGR) has been identified as a promising prognostic predictor of mortality in patients with hematological malignancies. This study investigated the prognostic significance of AGR in patients with multiple myeloma. METHODS: Two hundred patients diagnosed with multiple myeloma from January 2010 to October 2018 were retrospectively analyzed and followed up until December 2019. Kaplan-Meier curves and multivariate Cox regression analysis were applied to detect the prognostic value of AGR. RESULTS: The median follow-up period was 36 months. The optimal cutoff of AGR was 1.16 according to receiver operating characteristic curve analysis. High AGR was significantly correlated with better overall survival (OS) and progression-free survival (PFS). Multivariate analysis revealed that low AGR was an independent prognostic factor for worse OS (hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.15-2.94) and PFS (HR = 1.53, 95% CI = 1.09-2.17). CONCLUSIONS: AGR may represent a potential prognostic biomarker in patients with multiple myeloma.Mini Abstract: We demonstrated that high AGR was associated with a favorable overall survival and progression-free survival in patients with multiple myeloma.

Etodolac improves collagen induced rheumatoid arthritis in rats by inhibiting synovial inflammation, fibrosis and hyperplasia.

Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibrogenic factors Lum, CIV, CXI and Tgfbi participated in the synovial inflammation, fibrosis and hyperplasia in CIA. Based on KOG function class analysis, the proteins involved in the events of the central dogma was explored. They might be hyperplasia related proteins for most of them are related to the proliferation of cancer. ETD significantly attenuated synovial inflammation, fibrosis and hyperplasia in CIA rats by downregulating these proteins. Several proteins have not been observed in RA so far, such as Tmsb4x, Pura, Nfic, Ruvbl1, Snrpd3, U2af2, Srrm2, Srsf7, Elavl1, Hnrnph1, Wars, Yars, Bzw2, Mcts1, Eif4b, Ctsh, Lamp1, Dpp7, Ptges3, Cdc37 and Septin9, they might be potentials targets for RA. Blood biochemistry tests showed the safety of 7 months use of ETD on rats. In conclusion, present study displayed a comprehensive mechanism of synovial hyperplasia in CIA rats, on this basis, the clinical value of ETD in the treatment of RA was well confirmed.

Elevated TG/HDL-C and non-HDL-C/HDL-C ratios predict mortality in peritoneal dialysis patients.

BACKGROUND AND AIMS: Dyslipidemia is common in patients with chronic kidney disease and particular prevalent in patients receiving peritoneal dialysis. However, whether markers of atherogenic dyslipidemia correlate with outcomes in dialysis patients as in the general population is uncertain. The aim of this study was to explore the prognostic value of the serum triglyceride/HDL cholesterol (TG/HDL-C) ratio and non-HDL-C/HDL-C ratio to predict mortality in peritoneal dialysis patients. METHODS: Two hundred fourteen peritoneal dialysis patients were retrospectively analyzed from January 2011 to December 2015, with a median follow-up of 59 months. We used receiver operating curves (ROC) to determine the optimal threshold for TG/HDL-C and non-HDL/HDL-C ratios at baseline to predict overall survival during follow-up. Prognostic values were accessed by univariate and multivariate COX regression analysis and Kaplan-Meier curve. A predictive nomogram was developed to predict prognosis for overall survival, and the predictive accuracy was evaluated by concordance index (c-index). RESULTS: The optimal cut-off values for TG/HDL-C ratio and non-HDL-C/HDL-C ratio to predict mortality were 1.94 and 2.86, respectively. A high TG/HDL-C ratio and a high non-HDL-C/HDL-C ratio strongly correlated with worse overall survival in peritoneal dialysis patients. Multivariate analysis demonstrated that elevated TG/HDL-C ratio (HR 3.57, 95% CI 1.99, 6.39, P < 0.000) as well as non-HDL/HDL-C ratio (HR 2.58, 95%CI 1.39-4.81, P = 0.003) were independent markers to predict reduced OS. A nomogram was constructed to predict overall survival, with a c-index for predictive accuracy of 0.795. CONCLUSION: TG/HDL-C ratio and non-HDL-C/HDL-C may serve as potential prognostic biomarkers in PD patients.

Integrative proteomics and immunochemistry analysis of the factors in the necrosis and repair in acetaminophen-induced acute liver injury in mice.

Acetaminophen (APAP) overdose-induced acute liver injury (AILI) is a significant clinical problem worldwide, the hepatotoxicity mechanisms are well elucidated, but the factors involved in the necrosis and repair still remain to be investigated. APAP was injected intraperitoneally in male Institute of Cancer Research (ICR) mice. Quantitative proteome analysis of liver tissues was performed by 2-nitrobenzenesulfenyl tagging, two-dimensional-nano high-performance liquid chromatography separation, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry analysis. Diffrenetial proteins were verified by the immunochemistry method. 36 and 44 differentially expressed proteins were identified, respectively, at 24 hr after APAP (200 or 300 mg·kg -1 ) administration. The decrease in the mitochondrial protective proteins Prdx6, Prdx3, and Aldh2 accounted for the accumulation of excessive reactive oxygen species (ROS) and aldehydes, impairing mitochondria structure and function. The Gzmf combined with Bax and Apaf-1 jointly contributed to the necrosis. The blockage of Stat3 activation led to the overexpression of unphosphorylated Stat3 and the overproduction of Bax. The overexpression of unphosphorylated Stat3 represented necrosis; the alternation from Stat3 to p-Stat3 in necrotic regions represented hepatocytes from death to renewal. The high expressions of P4hα1, Ncam, α-SMA, and Cygb were involved in the liver repair, they were not only the markers of activated HSC but also represented an intermediate stage of hepatocytes from damage or necrosis to renewal. Our data provided a comprehensive report on the profile and dynamic changes of the liver proteins in AILI; the involvement of Gzmf and the role of Stat3 in necrosis were revealed; and the role of hepatocyte in liver self-repair was well clarified.

Identification of oncogenic long noncoding RNA SNHG12 and DUXAP8 in human bladder cancer through a comprehensive profiling analysis.

Bladder cancer is a common urological malignancies world-wide. Recently, a growing number of evidence have highlighted the importance of long noncoding RNAs (lncRNAs) in multiple cancers development and progression. However, the expression pattern of lncRNAs in bladder cancer and their underlying function remain poorly understood. To identify lncRNAs profile alterations and uncover valuable lncRNA candidates for bladder cancer diagnostic, we conducted a comprehensively lncRNAs profiling analyses and explored their clinical relevance using The Cancer Genome Atlas (TCGA) data and three independent microarray profiling data from the Gene Expression Omnibus (GEO). After annotation and analyses of these data, we found that lots of lncRNAs were dysregulated in bladder specimen when compared with normal control specimen. In addition, we found that differential expression of these lncRNAs is accompanied by genomic variations, including genome loci copy number deletion or amplification. Importantly, a part of these lncRNAs are related to bladder cancer patients outcome, such as SNHG10, SNHG12 and LINC00115. Finally, we validated two of these lncRNAs' (DUXAP8 and SNHG12) function in bladder cancer cells by down-regulating their expression with siRNAs, and found that down-regulation of DUXAP8 and SNHG12 could inhibit bladder cancer cells proliferation in vitro. In summary, this study demonstrated that a lot of lncRNAs are dysregulated in bladder cancer, and might provide useful lncRNAs resource for potential prognostic or diagnostic markers for this disease.

TAB3 promotes human esophageal squamous cell carcinoma proliferation and invasion via the NF­κB pathway.

Esophageal squamous cell carcinoma (ESCC) has become one of the most common causes of cancer­associated mortality worldwide. Transforming growth factor­activated kinase (TAK1)­binding protein 3 (TAB3) is essential for activation of the NF (NF)­κB pathway in response to TAK1 activation. The NF­κB pathway serves important roles in tumor cell proliferation and migration; however, the clinical relevance of TAB3 and its biological function in ESCC progression remain elusive. The present study investigated the expression and function of TAB3 in ESCC tissues, and its association with the clinical prognosis of patients. The results demonstrated that TAB3 expression was significantly increased in human ESCC cell lines and tissue samples, and the expression of TAB3 was associated with ESCC lymph node metastasis, T stage, pathological grade and Ki­67 expression in 80 ESCC samples, as determined by immunohistochemistry. Patients with ESCC and high TAB3 expression exhibited worse overall survival. Furthermore, knockdown of TAB3 by small interfering RNA inhibited the proliferation of ESCC cells, and reduced the migration and invasion of ESCC cells. In addition, knockdown of TAB3 decreased the expression of the NF­κB pathway in TE­1 cells. Taken together, these results demonstrated that TAB3 may be a promising therapeutic target for the treatment of ESCC.

Quantitative Proteomic Analysis Reveals That Arctigenin Alleviates Concanavalin A-Induced Hepatitis Through Suppressing Immune System and Regulating Autophagy.

Concanavalin A-induced autoimmune hepatitis is a well-established experimental model for immune-mediated liver injury. It has been widely used in the therapeutic studies of immune hepatitis. The in-depth analysis of dysregulated proteins from comparative proteomic results indicated that the activation of immune system resulted in the deregulation of autophagy. Follow-up studies validated that some immune related proteins, including Stat1, Pkr, Atg7, and Adrm1, were indeed upregulated. The accumulations of LC3B-II and p62 were confirmed by immunohistochemistry and Western blot analyses. Arctigenin pretreatment significantly alleviated the liver injury, as evidenced by biochemical and histopathological investigations, whose protective effects were comparable with Prednisone acetate and Cyclosporin A. Arctigenin pretreatment decreased the levels of IL-6 and IFN-γ, but increased the ones of IL-10. Next, the quantitative proteomic analysis demonstrated that ARC pretreatment suppressed the activation of immune system through the inhibition of IFN-γ signaling, when it downregulated the protein expressions of Stat1, P-Stat1, Pkr, P-Pkr, Bnip3, Beclin1, Atg7, LC3B, Adrm1, and p62. Meanwhile, Arctigenin pretreatment also reduced the gene expressions of Stat1, Pkr, and Atg7. These results suggested that Arctigenin alleviated autophagy as well as apoptosis through inhibiting IFN-γ/IL-6/Stat1 pathway and IL-6/Bnip3 pathway. In summary, the comparative proteomic analysis revealed that the activation of immune system led to Concanavalin A-induced hepatitis. Both autophagy and apoptosis had important clinical implications for the treatment of immune hepatitis. Arctigenin might exert great therapeutic potential in immune-mediated liver injury.

The relationship between coping styles and benefit finding of Chinese cancer patients: The mediating role of distress.

PURPOSE: To identify the relationship of medical coping styles and benefit finding in Chinese early-stage cancer patients by preliminary pilot study. METHOD: Three hundred and fifty one cancer patients were recruited from the Affiliated Jiangyin Hospital of Southeast University medical college and the Nantong Tumor Hospital in this study. Measurements were Chinese Benefit Finding Scale, Medical Coping Modes Questionnaire- Chinese version and Distress Thermometer. Regression analysis and pathway analysis were employed to identify the correlation of medical coping styles and benefit finding, and the mediating role of distress. RESULTS: Hierarchical regression analyses showed that confrontation coping style explained 24% of the variance in benefit finding, controlling for demographics and medical variables. While confrontation and resignation coping styles explained 10% and 6% of variance in distress separately. Pathway analyses implied that distress was found to mediate the effect of confrontation coping style on benefit finding in our study. CONCLUSIONS: Our study suggested an indirect association between medical coping styles and benefit finding, and a negative correlation of distress to medical coping styles and benefit finding. These results indicated that medical coping styles could influence benefit finding through distress.