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Oxidative stress (OS) is mediated by reactive oxygen species (ROS), which in cardiovascular and other disease states, damage DNA, lipids, proteins, other cellular and extra-cellular components. OS is both initiated by, and triggers inflammation, cardiomyocyte apoptosis, matrix remodeling, myocardial fibrosis, and neurohumoral activation. These have been linked to the development of heart failure (HF). Circulating biomarkers generated by OS offer potential utility in patient management and therapeutic targeting. Novel OS-related biomarkers such as NADPH oxidases (sNox2-dp, Nrf2), advanced glycation end-products (AGE), and myeloperoxidase (MPO), are signaling molecules reflecting pathobiological changes in HF. This review aims to evaluate current OS-related biomarkers and their associations with clinical outcomes and to highlight those with greatest promise in diagnosis, risk stratification and therapeutic targeting in HF.
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Background: Ursodeoxycholic acid (UDCA) is currently used for the treatment of primary biliary cholangitis (PBC), but some people do not respond well to UDCA. It reported that the combination of fenofibrate and UDCA can improve the clinical indices in these patients. However, more high-quality evidence is needed to improve guideline recommendations. Methods: Through an updated meta-analysis, studies included were valued by the Cochrane Evaluation Manual and Robins-I. Biochemical and clinical indicator changes in UDCA-refractory PBC patients receiving combination therapy were analyzed by Revman 5.42. Then, we explored the influence of fenofibrate dose and the effectiveness and safety of long-term application by retrospective cohort study. Results: Our meta-analysis included nine publications with a total of 389 patients, including 216 treated with UDCA alone and 173 who received combination therapy. The meta-analysis showed that combination therapy was more effective than UDCA monotherapy in decreasing biochemical parameters, such as ALP, GGT, IgM, and TG. However, the occurrence of pruritus and adverse events was slightly higher with combination therapy than with UDCA monotherapy. A total of 156 patients were included in our cohort study: 68 patients underwent UDCA monotherapy, and 88 patients underwent combination therapy. Among UDCA-refractory patients, fenofibrate add-on therapy significantly improved the ALP normalization rate. Conclusion: The combination of fenofibrate and UDCA can decrease biochemical parameters, of UDCA-refractory PBC patient. Furthermore, the efficacy and safety of long-term combination therapy were also confirmed in our cohort study.
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Objective To investigate the survival benefits of simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) in the treatment of esophageal squamous cell carcinoma ( ESCC ) . Methods From July 2003 to March 2014,1748 patients with ESCC received 3DCRT or IMRT in a single institution were enrolled in this retrospective study. Among them, 809 patients received conventional fractionated radiotherapy with the standard prescription dose and 110 patients received SIB-IMRT ( SIB-IMRT group).Survival analysis was performed and propensity score matching (PSM 1vs1) was conducted to evaluate and compare the survival benefits between SIB-IMRT and conventional fractionated radiotherapy. Results The baseline characteristics significantly differed between two groups. In the SIB group,the age was significantly younger ( 64 years vs. 66 years, P=0. 001 ) , the percentage of patients with cervical/upper thoracic tumors was considerably higher (53. 6％ vs. 31. 0％,P=0. 000) and the proportion of N2 patients was significantly higher ( 21. 8％ vs. 13. 7％,P=0. 027) compared with those in the other group. Accordingto the PSM of 1:1, 218 patients were successfully matched. After matching, the clinical data did not significantly differ between two groups. Prior to matching,the median survival time in the standard dose and SIB-IMRT groups were 23 and 21 months (P=0. 638).After matching,the median survival time in the SIB-IMRT group was 22 months,significantly longer than 18 months in the standard dose group (P=0. 000). Subgroup analysis demonstrated that patients with large tumors ( GTV volume>40 cm3 ) and middle/lower thoracic tumors obtained more survival benefits from SIB-IMRT. The median survival time of patients in the standard dose group was 14 months, significantly shorter than 21 months in the SIB-IMRT group ( P=0. 001).The median survival time of patients with middle/lower thoracic tumors in the SIB-IMRT group was 17 months,significantly longer than 9 months in the standard dose group (P=0. 000).Multivariate analysis using Cox regression model indicated that age, tumor site and radiotherapy modality were the independent prognostic factors. The HR of SIB-IMRT was 0. 551(P=0. 000),which was a factor for survival benefits. Conclusions SIB-IMRT possesses potential survival benefits for ESCC compared with conventional fractionated radiotherapy. Patients with large tumors and middle/lower thoracic tumors are more prone to obtaining benefits from SIB-IMRT than their counterparts.
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Objective To determine the efficacy of primary tumor of esophageal cancer,according to the result of magnetic resonance imaging before and after chemoradiotherapy of esophageal cancer,combined with clinical efficacy evaluation,and to verify the reliable evaluation of the short-term curative effect of magnetic resonance on esophageal cancer,combined with the original CT and esophagogram evaluation criteria.Methods From May 2010 to March 2014,totally 83 patients with esophageal carcinoma treated with 3D-CRT or IMRT were enrolled.The prescribed doses were ranged from 50-64 Gy with median dose of 60 Gy and 1.8-2.0 Gy per fraction,of which 34 of the patients received concurrent chemotherapy of FP or TP.All the patients performed the examinations of DWI,CT scan and esophagogram before and after radiotherapy.The treatment efficacy was evaluated by short-term therapeutic effect evaluation criterion of versions 1989 and 2013 and the hyperintense expression on DWI sequence.Results According to the short-term therapeutic effect evaluation criterion of versions 1989 and 2013 based on the examination of esophagogram and CT scan,45 patients achieved complete remission (CR) after treatment(54.2％) and 38 achieved partly remission(PR) (45.8％) version 1989,while 35 patients achieved CR (42.2％) and 48 achieved PR (57.8％) version vesion 2013.In the two differentcriterions,the local control rate and survival rate of the complete remission group in 1 to 5 years were better than those in the partial remission group.According to the examination of DWI,48 patients' hyperintense disappeared completely at the end of treatment (which was defined to CR),25 patients had a slightly hyperintense expression and 10 patients still had hyperintense expression on DWI sequence (which two defined to PR),the local control and survival rates of the former group were superior to the latter groups (x2 =6.125,11.652,P ＜0.05).The TE results evaluated by DWI and TE evaluation criterion of version 2013 were compared according to Kappa test,as a result,the Kappa coefficient 0.478.According to the examination of esophagogram,CT scan and DW1,25 patients achieved CR and 58 achieved PR in all exams,and the local control and survival rates of the former group were superior to the latter group (x2 =5.559,10.014,P ＜0.05).Conclusions The esophagogram and CT based TE evaluation criterion could well indicate local control status of esophageal cancer,and the examination of DWI could afford visualized and quantifying reference information about the TE of esophageal cancer.The expression of hyperintense at the end of treatment may indicate a high risk of recurrence and metastasis.The therapeutic effect evaluated by esophagogram,CT scan and DWI maybe more objective and more accurate.
