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Background: Chronic inflammation is known to be associated with both rotator cuff tears (RCTs) and depression. However, no epidemiological studies with a longitudinal follow-up have been performed to prove this association. We aimed to investigate whether depressed patients had an elevated risk of RCT and subsequent repair surgery compared with those without depression. Methods: This retrospective cohort study comprised of patients diagnosed with depression between 2000 and 2010 (depression cohort) and patients without depression (non-depression cohort, 1:2 age and sex matched). The risk of RCT and rotator cuff repair surgery were determined during a 13-year follow-up (2000–2013) between these two cohorts. Results: This study included 26,868 patients with depression and 53,736 patients without depression. The incidence of RCT was 648 and 438 per 100,000 person-years in the depression and non-depression cohorts, respectively. The adjusted hazard ratio (HR) was 1.46 (95% confidence interval [CI], 1.36–1.57) for depressed patients. The incidence of rotator cuff repair surgery was 28 and 18 per 100,000 person-years in the depression and non-depression cohorts, respectively. Depressed patients also had a significantly increased risk of subsequent rotator cuff repair surgery (adjusted HR = 1.46; 95% CI, 1.04–2.06). Conclusion: The present study showed that depression was associated with an i ncreased risk of rotator cuff tear and rotator cuff repair surgery. [ABSTRACT FROM AUTHOR]

The human erythrocyte contains an abundance of the thiol-dependant peroxidase Peroxiredoxin-2 (Prx2), which protects the cell from the pro-oxidant environment it encounters during its 120 days of life in the blood stream. In malarial infections, the Plasmodium parasite invades red cells and imports Prx2 during intraerythrocytic development, presumably to supplement in its own degradation of peroxides generated during cell metabolism, especially hemoglobin (Hb) digestion. Here we demonstrate that an irreversible Prx2 inhibitor, Conoidin A (2,3-bis(bromomethyl)-1,4-dioxide-quinoxaline; BBMQ), has potent cytocidal activity against cultured P. falciparum. Parasite growth was also inhibited in red cells that were treated with BBMQ and then washed prior to parasite infection. These cells remained susceptible to merozoite invasion, but failed to support normal intraerythrocytic development. In addition the potency of chloroquine (CQ), an antimalarial drug that prevents the detoxification of Hb-derived heme, was significantly enhanced in the presence of BBMQ. CQ IC50 values decreased an order of magnitude when parasites were either co-incubated with BBMQ, or introduced into BBMQ-pretreated cells; these effects were equivalent for both drug-resistant and drug-sensitive parasite lines. Together these results indicate that treatment of red cells with BBMQ renders them incapable of supporting parasite growth and increases parasite sensitivity to CQ. We also propose that molecules such as BBMQ that target host cell proteins may constitute a novel host-directed therapeutic approach for treating malaria. [ABSTRACT FROM AUTHOR]

Current anti-fibrotic effect of antioxidants in vivo is disappointing due probably to the fact that once liver fibrogenesis is established it is too advanced to be reversed by anti-oxidation mechanism. We consider antioxidant may only act on the early phase of fibrogenesis. Thus, we had previously established an early liver fibrosis animal model using an inducible expression vector (pPK9a), which contains TGF-β gene and was hydro-dynamically transferred into mice to induce a transient liver fibrosis. TGF-β1 has been well documented to up-regulate the expression of α2(1) collagen (Col 1A2) gene in the liver via the reactive oxygen species (ROS); the process triggers inflammation, leading to hepatic stellate cells (HSC) activation and liver fibrogenesis. Using our animal model and ROS, cyclooxygenase-2 (Cox-2) and Col 1A2 promoter assays as screening targets, we report here that a maleic acid derivative isolated from the Antrodia camphorata mycelium strongly decreases ROS production, promoter activity of Cox-2 and Col 1A2, intracellular calcium, expression of alpha-smooth muscle actin (α-SMA), Smad4-p-Smad2/3 co-localization in cell nucleus and the DNA binding activity of Sp1. Our results suggest that the maleic acid derivative prevents liver fibrosis at an early phase both in vitro and in vivo through the inhibition of ROS, inflammation and the activation of HSC. [ABSTRACT FROM AUTHOR]

The aim of the study was to use a previously proposed mask region–based convolutional neural network (Mask R-CNN) for automatic abnormal liver density detection and segmentation based on hepatocellular carcinoma (HCC) computed tomography (CT) datasets from a radiological perspective. Training and testing datasets were acquired retrospectively from two hospitals of Taiwan. The training dataset contained 10,130 images of liver tumor densities of 11,258 regions of interest (ROIs). The positive testing dataset contained 1,833 images of liver tumor densities with 1,874 ROIs, and negative testing data comprised 20,283 images without abnormal densities in liver parenchyma. The Mask R-CNN was used to generate a medical model, and areas under the curve, true positive rates, false positive rates, and Dice coefficients were evaluated. For abnormal liver CT density detection, in each image, we identified the mean area under the curve, true positive rate, and false positive rate, which were 0.9490, 91.99%, and 13.68%, respectively. For segmentation ability, the highest mean Dice coefficient obtained was 0.8041. This study trained a Mask R-CNN on various HCC images to construct a medical model that serves as an auxiliary tool for alerting radiologists to abnormal CT density in liver scans; this model can simultaneously detect liver lesions and perform automatic instance segmentation. [ABSTRACT FROM AUTHOR]

Purpose: Pterygium is an ocular surface disorder mainly caused by ultraviolet (UV) light exposure. This study explored the relationships between six cataract types with pterygium and UV exposure. Methods: We have previously studied cataracts in residents of three regions in China and Taiwan with different UV intensities. From that study, we identified 1,547 subjects with information on the presence or absence of pterygium. Pterygium severity was graded by corneal progress rate. Cataracts were graded by classification systems as three main types (cortical, nuclear, posterior subcapsular) and three subtypes (retrodots, waterclefts, fiber folds) with high prevalence in middle-aged and elderly people. We calculated the cumulative ocular UV exposure (COUV) based on subject data and National Aeronautics and Space Administration data on UV intensities and used logistic regression to calculate odds ratios for the associations of COUV, cataract, and pterygium. Results: We found an overall pterygium prevalence of 23.3%, with significant variation among the three regions. Four cataract types (cortical, nuclear, posterior subcapsular, and retrodots) were significantly associated with the presence of pterygium. Conclusions: There was a significant association between COUV and pterygium, indicating that COUV is associated with the risk of pterygium development and that pterygium is useful as an index of UV exposure. Furthermore, the type of cataract in eyes with pterygium may indicate the level of UV exposure. [ABSTRACT FROM AUTHOR]

Treatment with hydrogen peroxide (H2O2) raises the hatching rate through the development and diapause termination of Artemia cysts. To comprehend the upstream genetic regulation of diapause termination activated by exterior H2O2 elements, an Illumina RNA-seq analysis was performed to recognize and assess comparative transcript amounts to explore the genetic regulation of H2O2 in starting the diapause termination of cysts in Artemia salina. We examined three groupings treated with no H2O2 (control), 180 μM H2O2 (low) and 1800 μM H2O2 (high). The results showed a total of 114,057 unigenes were identified, 41.22% of which were functionally annotated in at least one particular database. When compared to control group, 34 and 98 differentially expressed genes (DEGs) were upregulated in 180 μM and 1800 μM H2O2 treatments, respectively. On the other hand, 162 and 30 DEGs were downregulated in the 180 μM and 1800 μM H2O2 treatments, respectively. Cluster analysis of DEGs demonstrated significant patterns among these types of 3 groups. GO and KEGG enrichment analysis showed the DEGs involved in the regulation of blood coagulation (GO: 0030193; GO: 0050818), regulation of wound healing (GO:0061041), regulation of hemostasis (GO: 1900046), antigen processing and presentation (KO04612), the Hippo signaling pathway (KO04391), as well as the MAPK signaling pathway (KO04010). This research helped to define the diapause-related transcriptomes of Artemia cysts using RNA-seq technology, which might fill up a gap in the prevailing body of knowledge. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin (Hb) levels are regarded as an important determinant of outcome in a number of cancers treated with radiotherapy. However, for patients treated with intensity modulated radiotherapy (IMRT), information regarding the prognostic value of hemoglobin level is scarce. Patients and Methods: A total of 650 patients with nasopharyngeal carcinoma (NPC), enrolled between May, 2005, and November, 2012, were included in this study. The prognostic significance of hemoglobin level (anemia or no-anemia) at three different time points was investigated, including before treatment, during treatment and at the last week of treatment. Univariate and multivariate analyses were conducted using the log–rank test and the Cox proportional hazards model, respectively. Results: The 5-year OS (overall survival) rate of patients who were anemia and no-anemia before treatment were 89.1%, and 80.7% (P = 0.01), respectively. The 5-year DMFS (distant metastasis-free survival) rate of patients who were anemia and no-anemia before treatment were 88.9%, and 78.2% (P = 0.01), respectively. The 5-year OS rate of patients who were anemia and no-anemia during treatment were 91.7% and 83.3% (P = 0.004). According to multivariate analysis, the pre-treatment Hb level predicted a decreased DMFS (P = 0.007, HR = 2.555, 95% CI1.294–5.046). Besides, the mid-treatment Hb level predicted a decreased OS (P = 0.013, HR = 2.333, 95% CI1.199–4.541). Conclusions: Hemoglobin level is a useful prognostic factor in NPC patients receiving IMRT. It is important to control the level of hemoglobin both before and during chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Hepatitis B virus reactivation is an important medical issue in cancer patients who undergo systemic chemotherapy. Up to half of CHB carriers receiving chemotherapy develop hepatitis and among these cases a notable proportion are associated with HBV reactivation. However, the molecular mechanism(s) through which various chemotherapeutic agents induce HBV reactivation is not yet fully understood. In this study, we investigated the role of the cell cycle regulator p21 (Waf1/Cip1) in the modulation of HBV replication when a common chemotherapeutic agent, doxorubicin, is present. We showed that p21 expression was increased by doxorubicin treatment. This elevation in p21 expression enhanced the expression of CCAAT/enhancer-binding protein α (C/EBPα); such an increase is likely to promote the binding of C/EBPα to the HBV promoter, which will contribute to the activation of HBV replication. Our current study thus reveals the mechanism underlying doxorubicin modulation of HBV replication and provides an increased understanding of HBV reactivation in CHB patients who are receiving systemic chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Intracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC. Methodology/Principal Findings: Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005–2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001) and stage II (90.5% VS 61.4%, P = 0.001) than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy), P = 0.67) and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11) was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01). Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87), progression-free survival rate (92.4% VS 86.5%, P = 0.41) and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64). Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57) and regional (95.0% VS 97.2%, P = 0.34) control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups. Conclusions/Significance: IMBT boost radiation may be a promising therapeutic selection for deep-seated residual NPC. [ABSTRACT FROM AUTHOR]

Previously, we have documented that isolated autophagosomes from tumor cells could efficiently cross-prime tumor-reactive naïve T cells and mediate tumor regression in preclinical mouse models. However, the effect of tumor-derived autophagosomes, here we refer as to DRibbles, on B cells has not been studied so far. At present study, we found that DRibbles generated from a murine hepatoma cell line Hep1-6, induced B-cell activation after intravenous injection into mice. B-cell populations were significantly expanded and the production of Hep1-6 tumor-specific antibodies was successfully induced. Moreover, in vitro studies showed that DRibbles could induce more efficient B-cell proliferation and activation, antibody production, and cytokine secretion than whole tumor cell lysates. Notably, we found that B-cell activation required proteins but not DNA in the DRibbles. We further showed that B cells could capture DRibbles and present antigens in the DRibbles to directly induce T cell activation. Furthermore, we found that B-cell activation, antibody production, cytokine secretion and antigen cross-presentation were TLR2-MyD88 pathway dependent. Taken together, the present studies demonstrated that tumor-derived autophagosomes (DRibbles) efficiently induced B cells activation, antibody production, cytokine secretion and antigen cross-presentation mainly depending on their protein component via TLR2/MyD88 dependent manner. [ABSTRACT FROM AUTHOR]

Background and Objectives: Studies investigating the association between glutathione S-transferase M1 (GSTM1) gene polymorphism and laryngeal cancer risk have reported conflicting results. The aim of the present study was to conduct a meta-analysis assessing the possible associations of GSTM1 gene polymorphism with laryngeal cancer risk. Methods: The relevant studies were identified through a search of PubMed, Embase, ISI Web of Knowledge and Chinese National Knowledge Infrastructure until May 2011 and selected on the basis of the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize association of GSTM1 polymorphism with laryngeal cancer susceptibility. Results: Seventeen studies were included instudies showed that GSTM1 null genotype was associated with increased laryngeal cancer risk (OR= 1.17, 95% CI = 1.04~1.31). When stratifying for race, GSTM1 null genotype exhibited increased laryngeal cancer risk in Caucasians (OR=1.15, 95% CI = 1.01~1.31), while no significant association was detected in Asians (OR=1.25, 95% CI = 0.80~1.96). In the subgroup analysis based on source of controls, significant associations were observed in the population-based studies (OR=1.15, 95% CI = 1.01~1.31) yet not in the hospital-based studies (OR = 1.25, 95% CI = 0.93~1.67). Furthermore, in the subgroup analysis based on sample size, significant associations were also found in studies with at least 50 cases and 50 controls (OR = 1.15, 95% CI = 1.02~1.30) but not in studies with fewer than 50 cases or 50 controls (OR = 1.46, 95% CI = 0.87~2.46). Conclusions: This meta-analysis supported that the GSTM1 gene polymorphism was associated with laryngeal cancer, particularly in Caucasians, and these associations varied in different subgroup, which indicated that population-based study with larger sample size was more appropriate in design of future study. [ABSTRACT FROM AUTHOR]