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Objective: In the present study, we attempted to identify the effects of fenofibrate on human cervical cancer cells. Methods: The cytotoxicity of fenofibrate in cervical cancer cells was determined by Cell Counting Kit-8. Immunoblotting assay was used to determine the protein expression of caspase-3, poly ADP-ribose polymerase cleavage, B-cell lymphoma 2 family protein expression, microtubule-associated protein 1A/1B-light chain 3 (LC3), as well as cyclins and cyclin-dependent kinases. Immunofluorescence imaging was used to determine the expression of cleaved caspase-3 and LC3. Flow cytometry was used to determine cell cycle and apoptosis. Results: We first showed that fenofibrate treatment reduced cell viability in HeLa cervical cancer cells in a dose-dependent manner at 24 h and 48 h. Importantly, fenofibrate-induced cell death was mediated through cell cycle arrest in the G0–G1 phase and caspase-dependent apoptosis. Moreover, fenofibrate also induced autophagy activation in a dose-dependent manner and pharmacological inhibition of autophagy led to increase of sub-G1 phase and caspase-dependent cell death in HeLa cells. Conclusion: In conclusion, these data demonstrated that fenofibrate initially induced cell cycle arrest, followed by caspase-3-dependent cell death in cervical cancer HeLa cells. However, fenofibrate also induced autophagy activation, which is closely related to the survival of diverse cancer cells, thus reducing the anticancer effects of fenofibrate. Therefore, the combination of an autophagy inhibitor and fenofibrate might have the potential to become a new therapeutic strategy for cervical cancer.

The COVID 19 pandemic is far from over, and vaccines remain important tool for fighting the disease. As the preventive effects of the COVID-19 vaccine emerges, it is likely that the perception of importance and safety of vaccines have a positive effect on the acceptance of other vaccines. However, it is still unclear how COVID-19 pandemic has affected the general vaccination perception and acceptance. Therefore, the objective of this study was to investigate the impact of the COVID-19 pandemic on the perception of HPV vaccination. This study involved an offline survey of 161 women aged between 20 and 49 years who visited the gynecologic clinic at Chung-nam National University Sejong Hospital from January 2021 to June 2021. The questionnaire consists of items related to experience and knowledge of COVID-19 and HPV viruses, as well as attitudes toward HPV vaccination. Knowledge about COVID-19 virus and HPV correlated positively with their experiences (P = .011 and P = .045, respectively). Positive attitude was increased, and negative attitude was reduced toward HPV vaccination in the COVID-19 pandemic era. Participants stated that accurate information and cost reduction about HPV vaccine was needed to increase the HPV vaccination rate. During the COVID-19 pandemic era, positive attitudes towards HPV vaccination have tended to increase. To increase the HPV vaccination rate, public efforts are needed for further information and cost reduction.

This study evaluated the efficacy and feasibility of long-term use of levonorgestrel releasing intrauterine system (LNG-IUS) in endometriosis patients after using LNG-IUS for5 years as their postoperative maintenance therapy.Data were obtained retrospectively from patients who maintained medical therapy for5 years after surgical treatment of endometriosis from January 2008 to April 2015. Patients were divided into study group and control group according to the type of medication; the study group consisted of patients who received LNG-IUS as maintenance therapy, and patients in the control group received combined oral contraceptives (ethinyl estradiol 20 μg and drospirenone 3 mg) or dienogest 2 mg.A total of 263 patients (94 patients in the study group, 169 in the control group) were included in the study. 91.5% (86/94) of the patients in the study group maintained the treatment for5 years, whereas only 21.9% (37/169) of patients in the control group maintained the treatment for5 years.LNG-IUS significantly decreased the pain score for non-cyclic pelvic/back pain (from 4.0 ± 1.6 to 0.6 ± 1.3, P .001), dysmenorrhea (from 6.5 ± 1.7 to 6.5 ± 1.7, P .001), and dyspareunia/dyschezia (from 6.5 ± 1.7 to 1.3 ± 1.4, P = .006) after 1 year, and the effect was persistent for 10 years (P .01). When compared with control group, the effect on pain reduction was comparable to the oral contraceptives or dienogest, with less systemic side effects such as mood change or nausea.LNG-IUS for5 years as a postoperative maintenance therapy for endometriosis patients is an effective and feasible treatment that shows significant effect on pain reduction with less systemic side effect compared with other types of treatment. Therefore, LNG-IUS can be recommended as a long-term postoperative therapy for endometriosis patients who do not plan to become pregnant for several years.

To evaluate the effect of pretreatment with combined oral contraceptives (COC) on outcomes in women with polycystic ovary syndrome (PCOS) who underwent assisted reproductive technology for subfertility. Two authors independently searched MEDLINE, EMBASE, and the Cochran Library to identify and review articles published from October 1995 until December 2018 according to selection criteria. Outcomes are expressed as mean difference and odds ratio (OR) in a meta-analysis model. A total of seven studies were included in this meta-analysis: one randomized controlled study and two prospective and four retrospective cohort studies. Meta-analysis showed that the COC pretreatment did not affect rate of clinical pregnancy (OR = 0.93, 95% confidence interval CI 0.65–1.34, I2 = 76%) or ovarian hyperstimulation syndrome (OR = 0.90, 95% CI 0.57–1.44, I2 = 0%). However, the rate of miscarriage in the COC group was significantly higher (OR = 1.33, 95% CI 1.02–1.72, I2 = 9%) and the rate of cumulative live birth was significantly lower compared with the control group (OR = 0.72, 95% CI 0.54–0.98, I2 = 55%). Subgroup analysis showed higher rates of miscarriage and lower rates of cumulative live birth in studies with a gonadotropin-releasing hormone (GnRH) antagonist protocol (OR = 1.69, 95% CI 1.17–2.44, I2 = 0% and OR = 0.38, 95% CI 0.29–0.50, respectively). Pretreatment with COC in women with PCOS before assisted reproductive technology may have an adverse effect on clinical outcomes, especially with a GnRH antagonist protocol.

To evaluate the efficacy and safety of a gonadotropin-releasing hormone (GnRH) agonist for treating large-sized submucosal leiomyoma before hysteroscopic myomectomy. The data were retrospectively collected from patients who underwent a hysteroscopic myomectomy for a submucosal leiomyoma3.5 cm in size from January 2009 to December 2018. The patients were divided into the GnRH group and the control group according to whether they were pretreated before surgery. A total of 61 patients were included in the study, 31 in the GnRH agonist group and 30 in the control group. At diagnosis, the maximum leiomyoma diameter was similar between the 2 groups (4.67 ± 0.6 cm in the GnRH agonist group vs 3.82 ± 0.6 cm in the control group, P = .061). After pretreatment with the GnRH agonist, the maximum diameter was significantly smaller in the GnRH agonist group compared to the control group (3.82 ± 0.6 vs 4.33 ± 0.8 cm, respectively, P = .004). The leiomyoma volume in the GnRH agonist group decreased by 55.6%, from 41.68 ± 15.7 to 23.19 ± 10.4 cm3, which led to significant differences in leiomyoma volume between the 2 groups (23.19 ± 10.4 cm3 in the GnRH agonist group vs 33.22 ± 24.7 cm3 in the control group, P = .042). The GnRH agonist group showed a shorter operation time (37.7 vs 43.9 minutes, P = .040) and less uterine distention media was used (6800 vs 9373.3 mL, P = .037) compared to the control group. Postoperative complications such as estimated blood loss, remnant leiomyoma, and recurrence were similar between the 2 groups. Treatment with a GnRH agonist before hysteroscopic myomectomy for large submucosal leiomyoma might decrease the volume of the leiomyoma, reduce operation time, and the amount of uterine-distension media used without surgical complications.

To evaluate the efficacy and feasibility of levonorgestrel-releasing intrauterine device (LNG-IUD) use longer than 5 years in women with adenomyosis.Data were retrospectively collected from patients who were treated with LNG-IUD longer than 5 years at the Chungnam National University hospital for adenomyosis diagnosed with ultrasonography from January 2006 to November 2013.A total of 131 patients who were diagnosed with adenomyosis had treated with LNG-IUD longer than 5 years. The mean duration of keeping 1 device without replacement was 58.35 ± 15.98 months, and total duration of LNG-IUD treatment was 83.86 ± 23.88 months. A total of 51 patients stopped using LNG-IUD after 5 years and the mean age at the time of LNG-IUD removal was 52.46 ± 6.9. LNG-IUD treatment had a significant effect on both menorrhagia and dysmenorrhea starting from the first month of insertion (P < .01), which persisted until 6 years when the effect started to plateau. The decrease in uterine volume was not consistent during the treatment period. The uterine volume decreased significantly only in the first and second year of LNG-IUD treatment and then from eighth to tenth year of LNG-IUD treatment (P < .05). Adverse events after insertion of LNG-IUD decreased significantly after 5 years.LNG-IUD treatment longer than 5 years is an effective and feasible method for patients diagnosed with adenomyosis.

Objective To compare the efficacy of levonorgestrel releasing intrauterine system (LNG-IUS) with other treatments as a postoperative maintenance therapy for endometriosis in terms of pain reduction, recurrence prevention, side effects and patients’ satisfaction. Study design We searched MEDLINE, EMBASE, and the Cochrane Library from January 1986 until February 2018. Two evaluators independently extracted and reviewed prospective and retrospective articles based on pre-determined selection criteria. Outcomes were expressed as mean difference (MD), risk ratios (RR) or odds ratios (OR) in a meta-analysis model, using Revman software. Results Among the 962 studies, 7 studies were selected: 7 studies included 4 randomized controlled trials with 212 patients, 1 prospective cohort study with 88 patients, and 2 retrospective studies with 191 patients. A meta-analysis showed that LNG-IUS was significantly effective in reducing pain after surgery (MD = 12.97, 95% confidence interval (CI): 5.55–20.39), with a comparable effect to gonadotropin-releasing hormone analogues (MD = −0.16, 95% CI: −2.02 to 1.70). LNG-IUS was also effective in decreasing the recurrence rate (RR = 0.40, 95% CI: 0.26–0.64), with an effect comparable to OC (OR = 1.00, 95% CI: 0.25–4.02) and danazol (RR = 0.30, 95% CI: 0.03–2.81). Furthermore, patients’ satisfaction with LNG-IUS was significantly higher than that with OC (OR = 8.60, 95% CI: 1.03–71.86). However, vaginal bleeding was significantly higher in the LNG-IUS group than in the gonadotropin-releasing hormone analogue group (RR = 27.0, 95% CI: 1.71–425.36). Conclusion Our meta-analysis found a positive effect of LNG-IUS as a postoperative maintenance therapy for endometriosis on pain relief, prevention of dysmenorrhea recurrence, and patients’ satisfaction.

To evaluate differences in microscopic findings and glucose transporter 3 (GLUT3) expression in terminal chorionic villi (TV) among birth weight-discordant twin (BWDT) placentas compared with the birth weight-concordant twin (BWCT) placentas.We retrospectively studied a cohort of 26 BWDT, 10 BWCT, 10 pre-eclampsia singleton and 10 normal singleton pregnancies. Placentas were scored for the percentage of TV, the percentage of TV with syncytial knots, the presence of capillary branching patterns of TV, the capillary to terminal villous ratios, the membranous expression of GLUT3 and the nuclear expression of HIF-1α in trophoblasts and capillary endothelial cells of TV using immunohistochemistry. The clinical characteristics and microscopic findings were analyzed and compared.BWDT placentas exhibited differential percentages of TV, percentages of TV with syncytial knots, capillary to terminal villous ratios, expression of HIF-1α in capillary endothelial cells and expression of GLUT3 in trophoblasts and capillary endothelial cells of TV among each twin pair compared with BWCT placentas (P=0.003, P=0.022, P=0.037, P=0.007, P=0.046 and P=0.002, respectively). Pre-eclampsia singleton placentas exhibited higher GLUT3 expression in trophoblasts, higher HIF-1α expression in capillary endothelial cells of TV and high capillary to terminal villous ratios compared with normal singleton placentas (P=0.001, P0.001 and P=0.001, respectively).We observed a strong relationship between characteristics of adaptive change to hypoxia (GLUT3 expression, TV and syncytial knotting and higher capillary to terminal villous ratios) and BWDT pregnancy but not BWCT pregnancy.