Cataract surgery is the most common intraocular procedure. To decrease postsurgical inflammation, prevent infection and reduce the incidence of secondary cataract, we built a temperature-sensitive drug delivery system carrying dexamethasone, moxifloxacin and genistein nanostructured lipid carrier (GenNLC) modified by mPEG-PLA based on F127/F68 as hydrogel. Characterizations and release profiles of the drug delivery system were studied. In vitro functions were detected by CCK-8 test, immunofluorescence, wound-healing assay, real time-PCR and western blotting. The size of GenNLCs was 39.47 ± 0.69 nm in average with surface charges of − 4.32 ± 0.84 mV. The hydrogel gelation temperature and time were 32 °C, 20 s with a viscosity, hardness, adhesiveness and stringiness of 6.135 Pa.s, 54.0 g, 22.0 g, and 3.24 mm, respectively. Transmittance of the gel-release medium was above 90% (93.44 ± 0.33% to 100%) at range of 430 nm to 800 nm. Moxifloxacin released completely within 10 days. Fifty percent of dexamethasone released at a constant rate in the first week, and then released sustainably with a tapering down rate until day 30. Genistein released slowly but persistently with a cumulative release of 63% at day 40. The thermoresponsive hydrogel inhibited the proliferation, migration and epithelial-mesenchymal transition of SRA 01/04 cells, which were confirmed by testing CCK-8, wound-healing assay, western blot, real time-PCR (RT-PCR) and immunofluorescence. These results support this intracameral thermoresponsive in situ multi-drug delivery system with programmed release amounts and release profiles to cut down the need of eye drops for preventing inflammation or infection and to reduce posterior capsular opacification following cataract surgery.
Background: Neoadjuvant radiotherapy has been shown to improve marginal negative resection and local control of Pancreatic Ductal Adenocarcinoma (PDAC). However, whether it improves overall survival (OS) in patients with non-metastatic PDAC remains controversial. Therefore, the purpose of this study was to analyze the benefits of only surgery, neoadjuvant radiotherapy, adjuvant radiotherapy, and surgery plus chemotherapy for OS in patients with non-metastatic PDAC. Methods: PDAC diagnosed by surgical histopathology in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016 was selected. Kaplan-Meier analysis was used to compare the prognosis of patients with different treatments. Cox proportional risk model was used to analyze independent predictors of OS. Propensity score matching (PSM) was used to analyze the tumor prognosis of different treatment methods. Results: Before PSM analysis, the OS of surgery plus chemotherapy (HRs = 0.896, 95%CIs, 0.827-0.970; P = 0.007) were significantly better than the other three treatments for stage T1-3N0M0 PDAC patients. For stage T1-3N + M0 patients, adjuvant radiotherapy (HRs = 0.613, 95% CIs, 0.579-0.649; P < 0.001) had significantly better OS than surgery plus chemotherapy and neoadjuvant radiotherapy. For stage T4N0M0 patients, neoadjuvant radiotherapy (HRs = 0.482, 95% CIs, 0.347-0.670; P < 0.001) had significantly better OS than surgery plus chemotherapy and adjuvant radiotherapy. For stage T4N + M0 patients, neoadjuvant radiotherapy (HRs = 0.338, 95% CIs, 0.215-0.532; P < 0.001) had significantly longer OS than adjuvant radiotherapy and surgery plus chemotherapy. Even after PSM, Chemotherapy plus surgery was still the best treatment for T1-3N0M0 patients. Postoperative adjuvant radiotherapy had the best prognosis among T1-3N + M0 patients, and neoadjuvant radiotherapy was the best treatment for T4 patients.
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