Braunarsenault1372

We developed a STAT3 silencing siRNA to both tumor cells and M2 macrophages. The dual-targeting system prepared by electronic self-assembly was composed of folic acid-conjugated carboxymethyl chitosan for targeting and cationic chitosan derivatives for siRNA package. The effects of siRNA delivery was investigated in M2 macrophages and Lewis lung cancer cells (LLC). Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibited a higher efficacy compared with non-targeting nanoparticles, resulting in a dramatically reduction of STAT3 expression in both cells, and a successful shift from M2 phenotypes (pro-tumor) to M1 phenotypes (anti-tumor) for macrophages. Additionally, the influence of the nanoparticles on LLC cells co-cultured with M2 macrophages was also investigated. The increased apoptosis and inhibition of proliferation of LLC cells were observed. In vivo therapeutic effect was also evaluated in s.c. tumor models, tumor growth was effectively inhibited and the level of M2 macrophages in tumor tissues was dramatically reduced. BACKGROUND Sporadic studies suggest hydroxychloroquine (HCQ) may be effective for thrombosis prevention in patients with primary antiphospholipid syndrome (PAPS) and may lead to antiphospholipid antibody (aPL) titer reduction but data from randomized studies are lacking. METHODS We conducted a pilot open-label randomized prospective study aiming to evaluate the safety and efficacy of HCQ for thrombosis prevention in 50 patients with PAPS allocated 11 to HCQ plus standard care (systemic anticoagulation and/or antiplatelet therapy) vs. standard care alone, as well as the effect of HCQ on aPL titers of 50 PAPS patients and 15 asymptomatic aPL carriers. RESULTS HCQ use plus standard care was associated with lower incidence rate of thrombosis than standard care alone (0.001 vs. 0.007, log-rank p =0.048) over an average 2.6-year follow-up, and a multivariate hazard ratio of 0.09 (95% CI = 0.01-1.26, p = 0.074) after adjusting for the effect of age, sex, traditional cardiovascular risk factors, triple aPL positivity, history of recurrent thrombotic events at baseline, and poor anticoagulation quality (INR levels within therapeutic range for ≤80% of follow-up). No significant difference in safety outcomes was observed between the two groups. Long-term HCQ use was associated with a decrease in aPL titers except for IgM anticardiolipin antibodies, which tended to decrease overtime regardless of treatment allocation. CONCLUSIONS HCQ may represent an effective adjuvant treatment for thrombosis prevention in patients with PAPS, which may be mediated via a reduction in aPL titers. Larger randomized trials are needed in order to corroborate this finding and investigate the thromboprotective role of HCQ in asymptomatic aPL carriers. OBJECTIVE To describe the incidence and progression of radiographic and symptomatic hand osteoarthritis (rHOA and sxHOA) in a large community-based cohort. DESIGN Data were from the Johnston County OA Project (1999-2015, 12 ± 1.2 years follow-up, age 45+). check details Participants had bilateral hand radiographs each visit, read for Kellgren-Lawrence grade (KLG) at 30 joints. We defined rHOA as KLG ≥2 in ≥1 joint. SxHOA was defined in a hand/joint with rHOA and self-reported symptoms or tenderness on exam. Incidence was assessed in those without, while progression was assessed in those with, baseline rHOA. Proportions or medians are reported; differences by sex and race were assessed using models appropriate for dichotomous or continuous definitions, additionally adjusted for age, education, body mass index (BMI), and weight change. RESULTS Of 800 participants (68% women, 32% African American, mean age 60 years), 327 had baseline rHOA and were older, more often white and female, than those without rHOA (n = 473). The incidence of HOA was high, for rHOA (60%) and for sxHOA (13%). Women were more likely than men to have incident HOA, particularly for distal interphalangeal joint radiographic osteoarthritis (DIP rOA) (adjusted odds ratios (aOR) 1.60 95% confidence intervals (95% CI) [1.03, 2.49]) and sxHOA (aOR 2.98 [1.50, 5.91]). Progressive HOA was more similar by sex, although thumb base rOA progressed more frequently in women than in men (aOR 2.56 [1.44, 4.55]). Particularly HOA incidence, but also progression, was more frequent among whites compared with African Americans. CONCLUSION This study provides much needed information about the natural history of HOA, a common and frequently debilitating condition, in the general population. STUDY OBJECTIVE To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). DESIGN A retrospective cohort study SETTING Asan Medical Center, Seoul, Korea PATIENTS Patients with International Federation of Obstetrics and Gynecology (FIGO) (2009) stage IB1-IIA HG NECC INTERVENTIONS All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. MEASUREMENTS AND MAIN RESULTS Between 1993 and 2017, 47 patients with FIGO stage IB1-IIA1 HG NECC were initially treated with RH. Clinicopathological variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1-42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH via MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph-node (LN) metastasis and resection margin (RM) involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018-4.871; P=0.045, and HR, 6.494; 95% CI, 1.415-29.809; P=0.016, respectively) and OS (HR, 3.236; 95% CI, 1.188-8.815; P=0.022, and HR, 12.710; 95% CI, 1.128-143.152; P=0.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs. 72.4% log-rank P=0.196, 38.9% vs. 37.9% P=0.975). CONCLUSION LN metastasis and RM involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.