Purpose: To unravel the role of interleukin (IL)-6 and insulinlike growth factor (IGF)-I receptor (IGFIR) in expressing stemnessrelated properties and to evaluate the prognostic values of pluripotent transcription factor OCT4/NANOG, and IGFIR in hepatocellular carcinoma (HCC).Experimental Design: Serum levels of IL6 were detected using ELISA assays (n ¼ 120). The effects of IL6/IGFI on stemness expression in HCC were examined using OCT4/ NANOG promoter luciferase reporter, RNA interference, secondary sphere formation, side population, and xenograft animal models. The OCT4/NANOG protein and phospho-IGFI receptor (p-IGFIR) in tissues were detected by Western blotting (n ¼ 8) and immunohistochemical staining (n ¼ 85). OCT4, NANOG, and IGFIR expression levels in tissues (n ¼ 191) were analyzed by real-time qRT-PCR and was correlated with early tumor recurrence using the Kaplan-Meier survival analysis.Results: A high positive correlation between the expression levels of OCT4/NANOG and IGFIR/p-IGFIR in human HCC tissues was observed. The concurrent expression of OCT4/ NANOG/IGFIR was mostly confined to hepatitis B virus (HBV)-related HCC (HBV-HCC) and was significantly correlated with early tumor recurrence. High serum levels of IL6 were significantly correlated with high OCT4/NANOG expression. IL6 stimulated an autocrine IGFI/IGFIR expression STAT3 dependently, which stimulated stemness-related properties in both the cell lines and the xenografted mouse tumors. The inhibition of IGFIR activation by either RNA interference or by treatment with the inhibitor picropodophyllin (PPP) significantly suppressed the IL6-induced stemness-related properties both in vitro and in vivo.Conclusions: The expression of pluripotency-related genes is associated with early tumor recurrence and is regulated by IL6-induced IGF/IGFIR activation, particularly in HBV-HCC.

BackgroundDiabetes mellitus (DM) correlates with accelerated aging and earlier appearance of geriatric phenotypes, including frailty. However, whether pre-frailty or frailty predicts greater healthcare utilization in diabetes patients is unclear.MethodsFrom the Longitudinal Cohort of Diabetes Patients in Taiwan (n = 840,000) between 2004 and 2010, we identified 560,795 patients with incident type 2 DM, categorized into patients without frailty, or with 1, 2 (pre-frail) and ≥ 3 frailty components, based on FRAIL scale (Fatigue, Resistance, Ambulation, Illness, and body weight Loss). We examined their long-term mortality, cardiovascular risk, all-cause hospitalization, and intensive care unit (ICU) admission.ResultsAmong all participants (56.4 ± 13.8 year-old, 46.1% female, and 84.8% community-dwelling), 77.8% (n = 436,521), 19.2% (n = 107,757), 2.7% (n = 15,101), and 0.3% (n = 1416) patients did not have or had 1, 2 (pre-frail), and ≥ 3 frailty components (frail), respectively, with Fatigue and Illness being the most common components. After 3.14 years of follow-up, 7.8% patients died, whereas 36.6% and 9.1% experienced hospitalization and ICU stay, respectively. Cox proportional hazard modeling discovered that patients with 1, 2 (pre-frail), and ≥ 3 frailty components (frail) had an increased risk of mortality (for 1, 2, and ≥ 3 components, hazard ratio [HR] 1.05, 1.13, and 1.25; 95% confidence interval [CI] 1.02–1.07, 1.08–1.17, and 1.15–1.36, respectively), cardiovascular events (HR 1.05, 1.15, and 1.13; 95% CI 1.02–1.07, 1.1–1.2, and 1.01–1.25, respectively), hospitalization (HR 1.06, 1.16, and 1.25; 95% CI 1.05–1.07, 1.14–1.19, and 1.18–1.33, respectively), and ICU admission (HR 1.05, 1.13, and 1.17; 95% CI 1.03–1.07, 1.08–1.14, and 1.06–1.28, respectively) compared to non-frail ones. Approximately 6–7% risk elevation in mortality and healthcare utilization was noted for every frailty component increase.ConclusionPre-frailty and frailty increased the risk of mortality and cardiovascular events, and entailed greater healthcare utilization in patients with type 2 DM.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0772-2) contains supplementary material, which is available to authorized users.

soriasis is a chronic inflammatory dermatosis that affects 0.1% to 3% of the adult population worldwide and results in a heavy economic burden. [1][2][3][4][5][6] Psoriasis has been associated with various comorbidities, including cardiovascular disease, stroke, diabetes mellitus, renal diseases, and arthritis. 7,8 Various studies reported that 6% to 42% of participants with psoriasis had concomitant psoriatic arthritis, while the percentage was lower among Asian people. 9 Psoriatic arthritis is an inflammatory joint disease that may lead to joint destruction and disability. 9 Uveitis is characterized by inflammation involving the uveal tract and associated ocular structures including the iris, ciliary body, and choroid tissue. 10 When affecting the anterior chamber, uveitis may present with pain and redness of the eye. When affecting the posterior chamber, eye pain and redness may not appear, but compromised visual acuity may occur. 11 Uveitis has been associated with psoriatic arthritis 12 and was more frequent and severe in the presence of human leukocyte antigen B27. 13 By contrast, the relationship between uveitis and psoriasis is still under investigation. 11 There have been a few studies examining the association between uveitis and psoriasis without psoriatic arthritis. A US case series reported that 9 patients with psoriasis without psoriatic arthritis had uveitis. 14 A cross-sectional study of 100 Singaporean patients with psoriasis found that the severity of psoriasis assessed by the Global Assessment score of the Lattice System Physician appeared to be higher among patients with uveitis than those without uveitis, although the difference did not reach statistical significance. 15 However, the Singaporean study did not find an association between uveitis and psoriatic arthritis. 15 A Turkish case-control study among 100 patients IMPORTANCE Uveitis has been associated with psoriatic arthritis, but to our knowledge, the relationship between uveitis and psoriasis is unsettled among researchers. OBJECTIVE To evaluate the risk of incident uveitis among people with psoriasis. DESIGN, SETTING, AND PARTICIPANTS This nationwide, retrospective cohort study conducted in Taiwan from January 1, 2000, to December 31, 2012 included 147 954 people with psoriasis (including 10 107 with concomitant psoriatic arthritis and 137 847 without psoriatic arthritis) and 147 954 nonpsoriatic controls. EXPOSURE Psoriasis. MAIN OUTCOMES AND MEASURES Risk of incident uveitis. RESULTSThe mean (SD) age of the 295 908 study participants was 44.4 (19.8) years, and 41.2% (n = 121 878) were women. We found that the group with severe psoriasis with psoriatic arthritis had the greatest risk of incident uveitis compared with the nonpsoriatic controls (adjusted hazard ratio, 2.40; 95% CI, 1.90-3.02). The group with severe psoriasis without psoriatic arthritis and the group with mild psoriasis with psoriatic arthritis also had an increased risk of incident uveitis (adjusted hazard ratio, 1.42; 95% CI, 1.23-1.64; and 1.42; 95% CI, 1.03-1.96; r...

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To examine the effect of frailty on diabetic kidney disease patients' risk of progression to end-stage renal disease (ESRD), mortality, and adverse episodes, as whether frailty modifies their risk of developing ESRD and other adverse outcomes remains unclear. We identified 165,461 DKD patients from the Longitudinal Cohort of Diabetes Patients in Taiwan (n=840,000) between 2004 and 2010, classifying them into those without frailty or with 1, 2 and ≥3 frailty components based on a modified version of FRAIL scale. Using Cox proportional hazard regression analysis, we examined the long-term risk of developing ESRD along with their risk of mortality, supplemented by a competing risk analysis against mortality. Among all participants, 66.2% (n=109,586), 27.2% (n=44,986), 5.9% (n=9,799), and 0.7% (n=1090) patients did not have or had 1, 2, and ≥3 frailty components, respectively. After a 4.1-year follow-up, 4.2% patients developed ESRD and 18.5% died. Cox proportional hazard modeling revealed that patients with 1, 2, and ≥3 frailty components had increased risks of developing ESRD (for 1, 2, and ≥3 components, hazard ratio [HR] 1.13, 1.18, and 1.2, respectively) and mortality (HR 1.25, 1.41, and 1.34, respectively), with. 9% and 16% risk elevations for ESRD and mortality per component increase. Competing risk analysis showed that frailty-induced ESRD risk was attenuated partially by mortality in those with moderate frailty. The receipt of palliative care did not attenuate this risk. Frailty increased the risk of ESRD based on a dose-response relationship among DKD patients with risk competition by mortality.

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ObjectivesDipeptidyl peptidase 4 inhibitor (DPP4i) use potentially slows the progression of diabetic kidney disease, but its effects on the risk of acute kidney injury (AKI) are unclear. We aimed to assess the association between DPP4i use and incident AKI episodes from a nationally representative cohort in Taiwan.Materials and MethodsAll patients newly diagnosed with diabetes mellitus (DM) between 2008, when DPP4i use was first approved in Taiwan, and mid-2013 were enrolled. Propensity score-matched diabetic DPP4i users, who received DPP4i for at least 90 days, and nonusers were selected. The primary and secondary outcomes were incident AKI and dialysis-requiring AKI during follow-up. Cox proportional hazard analyses were performed to examine the effect of DPP4i on the risk of AKI.ResultsWe enrolled 923,936 diabetic patients; of these, 83,638 DPP4i users (75.7% sitagliptin, 14.6% vildagliptin, and 9.7% saxagliptin) were propensity score-matched to 83,638 non-users. After an average 3.6-year follow-up, 1.56% and 0.35% of DPP4i users and 2.53% and 0.56% of non-users developed incident AKI and dialysis-requiring AKI, respectively. DPP4i use was significantly associated with lower risk of incident AKI (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.53–0.61) and risk of dialysis-requiring AKI (HR 0.57, 95% CI 0.49–0.66). The risk reduction was consistent regardless of DPP4i type, the presence of chronic kidney disease, the previous acute kidney injury, and age.ConclusionsDPP4i use is associated with reduced risk of mild and severe forms of AKI among patients with incident DM. DPP4i may be an important class of anti-glycaemic agent with reno-protective effects.

IntroductionWe compared the predictive ability of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to diagnose dementia in a community-based study.MethodsA total of 276 people aged 60 years or older were enrolled. All of the participants were administered face-to-face interview questionnaires and MoCA and MMSE examinations. The receiver operating characteristic curve method and area under curve were performed to assess the predictive ability for diagnosing dementia.ResultsThe 276 participants had a mean age of 67.9 ± 6.1 years and mean education duration of 11.4 ± 4.0 years. In general, the MoCA yielded higher AUCs (0.891) with favorable sensitivity (78 %) and excellent specificity (94 %) compared with the MMSE in differentiating the participants with and without dementia in either the total sample or all subgroups.ConclusionOur study determined a higher predictive ability in the MoCA than in the MMSE for diagnosing dementia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria in a community-based sample with a broader range of education level.