No abstract

Emerging evidence demonstrates that dysregulation of circular RNA is linked to tumorigenesis and aggressive progression. However, its role in oral squamous cell carcinoma remains largely uncharacterized. In this study, we identified a novel metastasis-associated circular RNA, circular matrix metalloproteinase 9 (hsa_circ_0001162, a circular RNA derived from matrix metalloproteinase 9), which was remarkably upregulated in oral squamous cell carcinoma and positively correlated with matrix metalloproteinase 9 expression. Patients with high circular matrix metalloproteinase 9 expression were prone to lymph node metastasis and an advanced TNM stage. Importantly, circular matrix metalloproteinase 9 was identified as an efficacious diagnostic and prognostic biomarker for oral squamous cell carcinoma patients. Functional experiments showed that depletion of circular matrix metalloproteinase 9 weakened the migratory and invasive capabilities of oral squamous cell carcinoma cells in vitro as well as inhibited lung metastasis in vivo. Regarding the mechanism, circular matrix metalloproteinase 9 could simultaneously interact with AUF1 and miR-149 to block the inhibitory effect of AUF1 and miR-149 on matrix metalloproteinase 9 3′-untranslated region, resulting in enhanced matrix metalloproteinase 9 messenger RNA stability, thereby facilitating oral squamous cell carcinoma metastasis. Collectively, our data indicate that circular matrix metalloproteinase 9 acts as a metastasis-promoting gene in oral squamous cell carcinoma through regulating the messenger RNA stability of its parental gene. Therapeutic targeting of circular matrix metalloproteinase 9 may be a promising treatment intervention for metastatic oral squamous cell carcinoma patients.

Purpose Elevated platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with poor outcomes in various diseases. The objectives of this study were to explore the utility of PLR and NLR in predicting all-cause mortality in patients with diabetic foot ulcers (DFU) undergoing amputations. Patients and Methods A retrospective observational study was performed that included a total of 348 DFU patients undergoing amputations. The primary end-point was all-cause death. According to the PLR and NLR cut-off values, patients were divided into two groups and Kaplan–Meier survival curves were constructed. Multivariable Cox regression was conducted to test the independent predictors of mortality in the study cohort. Results All-cause mortality was significantly higher in patients with a high PLR/NLR compared to those with a low PLR/NLR. In the low NLR group, the overall survival (OS) rates at 1, 3, and 5 years after amputation were 96.8%, 84% and 80.1%, respectively ( p =0.001). In the high NLR group the corresponding OS rates at 1, 3, and 5 years were 85.2%, 58.6% and 23.9% ( p <0.001). According to the multivariate analysis, age (HR 1.074, 95% CI 1.045–1.104, p<0.001), Wagner classification (HR 2.274, 95% CI 1.351–3.828, p=0.002), PLR (HR 1.794, 95% CI 1.014–3.174, p=0.045), NLR (HR 2.029, 95% CI 1.177–3.499, p=0.011), creatinine (HR 1.003, 95% CI 1.001–1.004, p<0.001) and direct bilirubin (HR 1.154, 95% CI 1.081–1.232, p<0.001) were independent predictors of mortality following amputation. Conclusion Postoperative PLR and NLR values may be reliable predictive biomarkers of mortality in patients following amputation for DFU. Considering the high mortality in those patients, the patients with elevated PLR/NLR should be given more intensive in clinical practice.

The aim of this study was to investigate 2 quantification criteria to evaluate the developmental condition of follicles cohort and clarify their impacts upon the determining of human chorionic gonadotropin trigger timing and the reproductive outcome: the proportion of mature follicles in growing follicles cohort on the day of human chorionic gonadotropin trigger and the peak estradiol level per oocyte on the day of human chorionic gonadotropin administration.Of the patients who underwent in vitro fertilization/ intracytoplasmic sperm injection-embryo transfer from 2011 to 2013, 492 controlled ovarian hyperstimulation cycles using gonadotropin-releasing hormone antagonists reaching the ovum pick-up and fresh embryo-transfer stage were included. Patients were divided into 3 groups according to their ≥17 mm/≥10 mm follicles ratio on the day of human chorionic gonadotropin administration (Low proportion: ≤30%, Middle proportion: 30%–60%, High proportion: ≥60%). Patients were divided into 5 groups according to their peak estradiol level/oocyte (Group A: <100 pg/mL per oocyte, Group B: 100–199 pg/mL per oocyte, Group C: 200–299 pg/mL per oocyte, Group D: 300–399 pg/mL per oocyte, Group E ≥400 pg/mL per oocyte) as well. Comparison among groups was made regarding ovarian stimulation characteristics, fertilization rate, good quality embryo rate, implantation, pregnancy, and live birth rates.On the basis of ≥17 mm/≥10 mm follicles ratio, the number of oocyte retrieved in low proportion group is more than other 2 groups. Implantation rate, clinical pregnancy, and live birth rate in high proportion group were 25.8%, 42.7%, and 31.1%, respectively, which is highest in 3 groups, and statistical significance existed between high and middle proportion groups. When the division is based on peak estradiol level/oocyte, the number of oocyte retrieved of ≥400 pg/mL per oocyte Group was significantly lowest compared with the other 4 groups. Matured ovum rate, fertilization rate, and good quality embryos rate exhibited an increasing trend as the peak estradiol level/oocyte increased. While pregnancy rate, implantation rate, and live birth rate were found to be lower whenever estradiol/oocyte ratio exceeded 400 pg/mL per oocyte or less than 100 pg/mL per oocyte, and there is statistical difference.Patients with the proportion of mature follicle reaching 60% on the day of human chorionic gonadotropin trigger and peak estradiol/oocyte level within 100∼399 pg/mL range can get a better pregnancy and implantation rate.