Both PK-TURBT and HoL-TURBT might prove to be preferable alternatives to CM-TURBT management of non-muscle invasive bladder cancer. PK-TURBT and HoL-TURBT, however, did not demonstrate an obvious advantage over CM-TURBT in tumor recurrence rate.
Clinical work and research on diabetic wound repair remain challenging globally. Although various conventional wound dressings have been continuously developed, the efficacy is unsatisfactory. The effect of drug delivery is limited by the depth of penetration. The sustained release of biomolecules from biological wound dressings is a promising treatment approach to wound healing. An assortment of cell-derived exosomes (exos) have been proved to be instrumental in tissue regeneration, and researchers are dedicated to developing biomolecules carriers with unique properties. Herein, we reported a methacrylate gelatin (GelMA) microneedles (MNs) patch to achieve transdermal and controlled release of exos and tazarotene. Our MNs patch comprising GelMA/PEGDA hydrogel has distinctive biological features that maintain the biological activity of exos and drugs in vitro. Additionally, its unique physical structure prevents it from being tightly attached to the skin of the wound, it promotes cell migration, angiogenesis by slowly releasing exos and tazarotene in the deep layer of the skin. The full-thickness cutaneous wound on a diabetic mouse model was carried out to demonstrate the therapeutic effects of GelMA/PEGDA@T + exos MNs patch. As a result, our GelMA/PEGDA@T + exos MNs patch presents a potentially valuable method for repairing diabetic wound in clinical applications.
Graphic Abstract
Injectable and degradable PEG hydrogel was prepared via Michael-type addition between cross-linking monomer 4-arm-PEG-MAL and two cross-linkers of hydrolysis degradable PEG-diester-dithiol and non-degradable PEG-dithiol, and it had a porous structure with the uniform pore size. The biocompatibility assays in vitro indicated that PEG hydrogel had excellent biocompatibility and can be degraded naturally without leading to any negative impact on cells. The results of antibacterial experiments showed that PEG hydrogel can inhibit the growth of bacteria. Furthermore, the Cell Counting Kit-8 (CCK-8) assay, LIVE/DEAD cell staining, and scratch healing experiments proved that PEG hydrogel can promote cell proliferation and migration, which had been further confirmed in in vivo experiments on the rat wound models. All experimental results demonstrated that PEG hydrogel is an injectable antibacterial dressing, which can promote the process of wound healing and has great potential in the field of wound healing.
The prognostic role of programmed death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) has been widely studied but the results are controversial. In this comprehensive meta-analysis, we elucidated the clinical value of PD-L1 in HCC. Relevant studies were systematically searched in the Cochrane Library, EMBASE, and PubMed until June 27, 2019. Eligible studies were validated for the prognostic effect of PD-L1 on the overall survival (OS), disease-free survival (DFS), and relapse-free survival (RFS) in HCC using a hazard ratio (HR) and its 95% confidence interval (95% CI). Twenty-three studies with 3529 patients were involved in this meta-analysis. The pooled results revealed that high membrane-bound PD-L1 (mPD-L1) expression was associated with poor OS (HR: 1.42; 95% CI: 1.12–1.80; P = 0.004) and had no significant correlation with RFS (HR: 1.14; 95% CI: 0.85–1.54; P = 0.39), and DFS (HR: 1.36; 95% CI: 0.81–2.28; P = 0.25). The results also indicated that high soluble PD-L1 (sPD-L1) levels were associated with worse OS (HR: 2.93; 95% CI: 2.20–3.91; P < 0.00001). In addition, high mPD-L1 expression was associated with high alpha-fetoprotein levels (AFP; OR = 1.46; 95% CI: 1.16–1.84; P = 0.001), hepatitis (OR = 0.72; 95% CI: 0.54–0.98; P = 0.03), poor tumor differentiation (OR = 0.68; 95% CI: 0.55–0.84; P = 0.03), and tumor-infiltrating lymphocytes (OR = 3.39; 95% CI: 1.06–10.91; P = 0.04). The mPD-L1 expression had no significant correlation with age, number of tumors, gender, tumor size, liver cirrhosis, vascular invasion, tumor encapsulation, or TNM stage. The study revealed that high mPD-L1 expression in the tumor tissue and high sPD-L1 levels were associated with shorter OS in HCC. Moreover, overexpression of mPD-L1 was significantly associated with poor tumor differentiation, hepatitis, AFP elevation, and tumor-infiltrating lymphocytes.
BackgroundObesity is a growing problem worldwide and can often result in a variety of negative health outcomes. In this study we aim to apply partial least squares (PLS) methodology to estimate the separate effects of age, period and cohort on the trends in obesity as measured by body mass index (BMI).MethodsUsing PLS we will obtain gender specific linear effects of age, period and cohort on obesity. We also explore and model nonlinear relationships of BMI with age, period and cohort. We analysed the results from 7,796 men and 10,220 women collected through the SLAN (Surveys of Lifestyle, attitudes and Nutrition) in Ireland in the years 1998, 2002 and 2007.ResultsPLS analysis revealed a positive period effect over the years. Additionally, men born later tended to have lower BMI (−0.026 kg·m-2 yr-1, 95% CI: -0.030 to −0.024) and older men had in general higher BMI (0.029 kg·m-2 yr-1, 95% CI: 0.026 to 0.033). Similarly for women, those born later had lower BMI (−0.025 kg·m-2 yr-1, 95% CI: -0.029 to −0.022) and older women in general had higher BMI (0.029 kg·m-2 yr-1, 95% CI: 0.025 to 0.033). Nonlinear analyses revealed that BMI has a substantial curvilinear relationship with age, though less so with birth cohort.ConclusionWe notice a generally positive age and period effect but a slightly negative cohort effect. Knowing this, we have a better understanding of the different risk groups which allows for effective public intervention measures to be designed and targeted for these specific population subgroups.
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