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Background/Aim: The purpose of this study was to investigate whether bone morphogenetic protein (BMP)-4 expression differs according to the presence of calcification in papillary thyroid carcinoma and to investigate if calcification and BMP-4 expression are associated with metastasis of papillary carcinoma.Methods: We performed the study using paraffin-embedded tissues of 55 patients who underwent thyroidectomy in Kosin University Gospel Hospital. Of those 55 cases, 36 were papillary thyroid carcinomas, and 19 were benign tumors. Immunohistochemical staining with BMP4 antibody was performed on the paraffin-embedded tissues.Results: Among the 36 papillary thyroid carcinomas, 20 (55.6%) of extrathyroidal invasion and 21 (58.3%) of lymph node metastasis were observed. The presence of calcification was significantly different according to incidence of extranodal invasion (p = 0.02), lymphovascular invasion (p < 0.001), and lymph node metastasis (p = 0.04). BMP-4 expression was weakly positive in benign tumors and strongly positive in papillary thyroid carcinoma (p < 0.001). BMP-4 expression was significantly different by TNM stage (p < 0.001).Conclusion: In the present study, the presence of calcification in thyroid papillary carcinoma was associated with tumor metastasis. BMP-4 was strongly expressed in papillary thyroid carcinoma and was associated with the stage of papillary thyroid carcinoma.

Subacute thyroiditis is an inflammatory thyroid disease caused by viral infection. Graves’ disease is an autoimmune thyroid disease caused by thyrotropin (TSH) receptor antibody (TRAb). Graves’ disease following subacute thyroiditis is rare, and only a few cases have been reported. A 58-year-old woman presented with anterior neck pain and swallowing difficulty. Laboratory tests showed elevated FT4, low TSH, normal TRAb, and elevated erythrocyte sedimentation rate. Thyroid ultrasonography (US) revealed focal, ill-defined hypoechoic areas in both thyroid lobes. The patient was treated with corticosteroid, and symptoms subsided after 1 month. Three months later, she complained of tremor and palpitation. Thyroid function testing showed hyperthyroidism with the positive conversion of TRAb, indicating Graves’ disease. Doppler US showed increased vascular flow in both thyroid lobes. She started treatment for hyperthyroidism with methimazole.

Background This case report presents a case of Vulvar Crohn’s disease (VCD) in an adolescent, that is an uncommon manifestation of Crohn’s disease (CD) without gastrointestinal symptoms. Before treating CD itself with proper medication, vulvar abscess continued to recur without improvement. Case presentation We report the case of an 18-year-old woman with VCD. After treatment with azathioprine 50 mg daily and mesalazine 1 g three times daily, vulvar lesions resolved after 6 weeks. We collected electronic medical data on patient characteristics, and evaluated findings of physical examinations, pelvic MRI, and biopsy specimen obtained from gastroduodenoscopy/colonoscopy. Conclusions VCD is a rare manifestation of CD that may be misdiagnosed in the absence of gastrointestinal symptoms leading to delayed treatment. If a patient has an unexplained vulvar inflammatory lesion and with repeated failed surgical treatment, gynecologists should consider the possibility of a VCD.

Objectives It is well known that type 2 diabetes (T2DM) is dramatically improved after bariatric surgery, although the mechanisms have not been clearly identified. The skill required for gastric surgery for gastric cancer is very similar to that needed in bariatric surgery. In this study, we evaluated the immediate improvement of T2DM after gastrectomy for gastric cancer. Methods A total of nine patients who were diagnosed with early gastric cancer (EGC) and already had T2DM underwent a 75 g oral glucose tolerance test (OGTT) before surgery and within two weeks after gastrectomy. Glucose, insulin, and c-peptide were measured before, and 30 and 60 minutes after ingesting 75 g of glucose. From these trials, we calculated the HOMA-IR, insulinogenic index, Matsuda index, and area under the curve (AUC). Results The mean age of participants was 57.23 ± 11.08 years and eight of them were men. HOMA-IR (4.2 vs. 2.3, P = 0.012) levels were decreased after surgery. There were no significant differences of insulinogenic index, fasting blood sugar before and after surgery. The Matsuda index (3.3 vs. 8.3, P = 0.002) was significantly increased and AUC (512.9 vs. 388.7 mg-hr/dL, P > 0.001) upon 75 g OGTT was significantly decreased after surgery. Conclusions Insulin sensitivity was immediately improved after gastrectomy for early gastric cancer in patients with T2DM.

Ovaries are the primary physiological source of female sex hormones, which play a crucial role in maintaining ovarian cycle, determining secondary sexual characteristics and preparing the endometrium for implantation. In vitro follicle engineering has been used to investigate follicle development, including ovarian hormone production and gamete maturation. To engineer functional follicles, culture and expansion of the primary ovarian cells are essential. However, the phenotypic and functional characteristics of primary ovarian cells are often lost during culture. The objective of this study is to develop an optimized culture system for maintaining ovarian cell growth and functionality. Granulosa cells (GCs) and theca cells (TCs) were isolated from female rats. The addition of follicle-stimulating hormone (FSH) or luteinizing hormone (LH) to the basal culture media significantly enhanced the secretion of estradiol from GCs and androstenedione from TCs. Serum concentrations of 5% and 10% had a similar role in promoting ovarian cell expansion and secretion of estradiol and androstenedione hormones from both types of cells. Growth differentiation factor 9 (GDF9), bone morphogenic protein 15 (BMP15), BMP7 and basic fibroblast growth factor (bFGF) enhanced GC proliferation and estradiol production, respectively. Among them, the effect of bFGF was most significant. bFGF also enhanced TC proliferation. When GCs and TCs were cultured in 5% serum, gonadotropin and bFGF-containing medium, they proliferated exponentially throughout the culture period of up to 40 days while maintaining their functional characteristics. Taken together, these results indicate that our medium formula is optimal for maximizing proliferation of functionally differentiated ovarian cells.

Advances in anticancer treatments have resulted in increasing survival rates among cancer patients. Accordingly, the quality of life after treatment, particularly the preservation of fertility, has gradually emerged as an essential consideration. Cryopreservation of embryos or unfertilized oocytes has been considered as the standard method of fertility preservation among young women facing gonadotoxic chemotherapy. Other methods, including ovarian suppression and ovarian tissue cryopreservation, have been considered experimental. Recent large-scale randomized controlled trials have demonstrated that temporary ovarian suppression using gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy is beneficial for preventing chemotherapy-induced premature ovarian insufficiency in breast cancer patients. It should also be emphasized that GnRHa use during chemotherapy does not replace established fertility preservation methods. All young women facing gonadotoxic chemotherapy should be counseled about and offered various options for fertility preservation, including both GnRHa use and cryopreservation of embryos, oocytes, and/or ovarian tissue.

Although menopausal hormone therapy (MHT) is the most effective approach to managing the loss of ovarian activity, serious side effects have been reported. Cell-based therapy is a promising alternative for MHT. This study constructed engineered ovarian cell spheroids and investigated their endocrine function. Theca and granulosa cells were isolated from ovaries of 10-week-old rats. Two types of engineered ovarian cell spheroids were fabricated through forced aggregation in microwells, multilayered spheroids with centralized granulosa aggregates surrounded by an outer layer of theca cells and mixed ovarian spheroids lacking spatial rearrangement. The ovarian cell spheroids were encapsulated into a collagen gel. Non-aggregated ovarian cells served as controls. The endocrine function of the engineered ovarian spheroids was assessed over 30 days. The structure of the spheroids was well maintained during culture. The secretion of 17β-estradiol from both types of engineered ovarian cell spheroids was higher than in the control group and increased continuously in a time-dependent manner. Secretion of 17β-estradiol in the multi-layered ovarian cell spheroids was higher than in the non-layered constructs. Increased secretion of progesterone was detected in the multi-layered ovarian cell spheroids at day 5 of culture and was sustained during the culture period. The initial secretion level of progesterone in the non-layered ovarian cell spheroids was similar to those from the controls and increased significantly from days 21 to 30. An in vitro rat model of engineered ovarian cell spheroids was developed that was capable of secreting sex steroid hormones, indicating that the hormone secreting function of ovaries can be recapitulated ex vivo and potentially adapted for MHT.

Objectives The microRNAs (miRNAs) are known to be commonly expressed in papillary thyroid carcinoma. The BRAFV600E mutation is the most common genetic mutation in thyroid cancer. The main aim of this study was to determine the possible association between expression of the three miRNAs and that of BRAFV600E mutation and the clinicopathological features in papillary thyroid carcinoma. Methods This study was conducted on 51 paraffin-embedded tissues (42 thyroid cancer, 9 benign tumor) obtained from patients undergoing thyroidectomy at the Endocrine Center of OOO University Hospital. Results miRNAs expression was significantly high in patients with cervical lymph node metastasis and advanced TNM stage. In addition, miR-146b expression levels were significantly higher in papillary thyroid carcinoma patients with BRAFV600E mutation. The relative quantification (2-ΔΔCt) of miR-146b was also high among the miRNAs. Individually, the AUCs for miRNA-146b was 0.923 (cutoff value −1.97, sensitivity 88.9%, specificity 85.7%). Conclusions Especially, expression of miR-146b increased higher in PTC patients with BRAFV600E mutation. These findings showed a role of miR-146b as potential biomarkers in differentiating PTC from benign tumor and as a prognostic indicator of PTCs. Further investigation will need for the roles of miRNAs in the pathogenesis of papillary thyroid carcinomas.

Endometriosis is a common gynecologic disorder characterized by chronic pelvic pain, dysmenorrhea, and infertility. Although this condition places significant financial burden on the healthcare system and negatively affects patient's quality of life, the pathophysiology of the disease remains unclear, and noninvasive diagnostic methods are insufficient. The object of this study was to identify potential biomarkers for endometriosis from peripheral blood. We hypothesized that serum biomarkers modified in endometriosis patients would be detected by multiplex cytokine panel, and identification of a combination of these biomarkers would improve diagnostic power. A total of 141 women, aged 15-52 years with regular menstruation, participated in this study. Twenty-one serum cytokines were detected using the commercially available MILLIPLEX MAP Human Cytokine/Chemokine Kit Panel IV. Among these cytokines, breast- and kidney-expressed chemokine (BRAK)/chemokine (C-X-C motif) ligand 14 (CXCL14) was significantly decreased, and proliferation-inducing ligand (APRIL)/tumor necrosis factor ligand superfamily member 13 (TNFSF13) was significantly increased in endometriosis group. APRIL/TNFSF13 and BRAK/CXCL14 alone or in combination, however, failed to show adequate sensitivity or specificity for the diagnosis of endometriosis. Combination of APRIL/TNFSF13 and BRAK/CXCL14 with serum CA-125 levels yielded significantly higher sensitivity (71.2%) for detecting endometriosis without compromising specificity (80.8%) than CA-125 alone in a logistic regression model (P = 0.050). In conclusion, we identified a biomarker combination that detects endometriosis better than CA125 alone. Therefore, we conclude that multiplex cytokine panel is an efficient method for detecting endometriosis, and analysis of additional cytokine panels may lead to identification of a novel biomarker combination with superior diagnostic power.

Objective The aim of this study was to present experiences in localization and removal of non-palpable subdermal contraceptive implants with ultrasonography. Methods Medical records from January 1, 2016, to April 30, 2018, were retrospectively reviewed for 21 patients who were referred to a single institution and had an impalpable implant despite following the removal instruction. In all the cases, more than one attempt was made to remove the implant before referral. The rod was detected using radiography and ultrasonography. In all the cases, localization of the single implant was achieved with ultrasonography. The distal depth of the rod was measured, and skin marking was made following the echogenicity. The implants were subsequently removed under anesthesia. Results In 18 cases, the rods were localized using ultrasonography and successfully removed under local anesthesia. In the other three cases, removal with local anesthesia failed. Although the rod was detected successful with ultrasonography, the implants were removed under general anesthesia in the operating room. The depth from skin to rod, measured with ultrasonography, was >12.0 mm in all the cases and located deep in the muscular layer in the failure cases. The depth of the implants positively correlated with the time spent for removal (r=0.525; P=0.015). Conclusion High frequency ultrasonography is a highly accurate tool for localization and measurement of the skin-to-rod depth. It is also useful for removing non-palpable implants. If the depth of the implant is >12.0 mm, removal of the implant in the operating room under general anesthesia is recommended.

Background Despite the good prognosis in patients with transplant organs, limited evidence is available on how immunosuppressants affect pregnancy. The aim of this study was to determine whether immunosuppressant use affects the pregnancy outcome and to identify whether there is any need to change the immunosuppressant before the patient tries to conceive. Methods This retrospective cohort study included women with previous kidney transplantation history who visited the Department of Obstetrics and Gynecology for either infertility or antenatal care between January 2005 and May 2016. A total of 40 cases (36 women) met the inclusion criteria. Statistical analyses were performed using SAS version 9.4. Results There were no differences in the immunosuppressant regimen between the pregnant and non-pregnant groups (never-pregnant+miscarriage) (P = 0.73). Individual immunosuppressant use was significantly different in terms of pregnancy outcome among the never-pregnant, miscarriage, and clinical pregnancy groups (azathioprine, P = 0.01; deflazacort, P

Background This study aimed to evaluate the compatibility of robotic single-site (RSS) myomectomy in comparison with the conventional robotic multi-port (RMP) myomectomy to achieve successful surgical outcomes with reliability and reproducibility. Methods This retrospective case–control study was performed on 236 robotic myomectomies at a university medical center. After 1:1 propensity score matching for the total myoma number, total myoma diameter, and patient age, 90 patients in each group (RSS: n = 90; RMP: n = 90) were evaluated. Patient demographics, preoperative parameters, intraoperative characteristics, and postoperative outcome measures were analyzed. Results The body mass index, parity, preoperative hemoglobin levels, mean maximal myoma diameter, and anatomical type of myoma showed no mean differences between RSS and RMP myomectomies. The RSS group was younger, had lesser number of myomas removed, and had a smaller sum of the maximal diameter of total myomas removed than the RMP group. After propensity score matching, the total operative time (RSS: 150.9 ± 57.1 min vs. RMP: 170 ± 74.5 min, p = 0.0296) was significantly shorter in the RSS group. The RSS group tended to have a longer docking time (RSS: 9.8 ± 6.5 min vs. RMP: 8 ± 6.2 min, p = 0.0527), shorter console time (RSS: 111.1 ± 52.3 min vs. RMP: 125.8 ± 65.1 min, p = 0.0665), and shorter time required for in-bag morcellation (RSS: 30.1 ± 17.2 min vs. RMP: 36.2 ± 25.7 min, p = 0.0684). The visual analog scale pain score 1 day postoperatively was significantly lower in the RSS group (RSS: 2.4 ± 0.8 days vs. RMP: 2.7 ± 0.8 days, p = 0.0149), with similar consumption of analgesic drugs. The rate of transfusion, estimated blood loss during the operation, and length of hospital stay were not different between the two modalities. No other noticeable complications were observed in either group. Conclusions Da Vinci RSS myomectomy is a compatible option with regard to reproducibility and safety, without significantly compromising the number and sum of the maximal diameter of myomas removed. The advantage of shorter total operative time and less pain with the same amount of analgesic drugs in RSS myomectomy will contribute to improving patient satisfaction.

The aim of this study was to determine predictive factors for pregnancy and assess the cumulative pregnancy rate (CPR) and live birth rate (CLBR) in subfertile couples undergoing timed intercourse (TI) using ultrasound. This retrospective cohort study included 285 women (854 cycles) who started TI with ultrasound between January 2017 and October 2019. The overall clinical pregnancy rate was 28.1% (80/285) per couple and 9.4% (80/854) per cycle. Pregnant women had a higher body mass index (BMI), higher percentage of irregular menstrual cycles, a shorter duration of subfertility, lower serum follicle-stimulating hormone levels, and higher anti-Müllerian hormone levels than non-pregnant women. A longer duration of subfertility (≥24 months vs. vs. ovulatory factors; odds ratio: 0.282; 95% confidence interval: 0.106-0.746) as causes of subfertility were unfavorable factors that independently affected clinical pregnancy. In subgroup analysis, old age ≥ 35 years [vs. < 35 years; odds ratio: 0.279; 95% confidence interval: 0.083-0.938), a longer duration of infertility ≥24 months (vs. 2(vs. >25 kg/m2; odds ratio: 3.202; 95% confidence interval: 1.020-10.046) in couples with ovulatory factor and a longer duration of infertility ≥24 months (vs.

Purpose This study aimed to elucidate whether microRNA-139-5p is involved in the pathogenesis of uterine leiomyoma. Materials and methods Human leiomyoma and matched human smooth muscle samples were obtained from 10 women who underwent hysterectomy for uterine leiomyoma. MicroRNA (miRNA) expression was analyzed by quantitative real-time polymerase chain reaction. To assess the effects of miR-139-5p on cultured leiomyoma cells, cell migration, collagen gel contraction, wound healing, and the expression levels of hallmark proteins were evaluated in cells transfected with a miR-139-5p mimic. Results The expression of miR-139-5p was significantly lower in leiomyoma tissues than in matched smooth muscle tissues. Restored miR-139-5p expression in miR-139-5p mimic-transfected human leiomyoma cells resulted in decreased contractility of the ECM and cell migration. In addition, upregulation of miR-139-5p decreased the protein expression of collagen type 1 and phosphorylated p38 MAPK. Conclusion Expression of miR-139-5p is downregulated in leiomyoma cells and modulation of miR-139-5p may be involved inthe pathogenesis of leiomyomas through the regulation of collagen type 1 and phosphorylated p38 MAPK. Therefore, miR-139-5p is a potential therapeutic target for leiomyoma.

To evaluate risk factors leading to non-alcoholic fatty liver disease (NAFLD) occurrence in polycystic ovarian syndrome (PCOS) women. A retrospective cohort study of a total of 586 women diagnosed with PCOS aged 13–35 years at the gynecology department at a university hospital was done to evaluate PCOS phenotype, metabolic syndrome (MetS) diagnosis, body composition, insulin sensitivity, sex hormones, lipid profile, liver function, and transient elastography (TE). In PCOS women with NAFLD compared to those without, MetS diagnosis (Hazard ratio [HR] 5.6, 95% Confidence interval [CI] 2.2–14.4, p p = 0.01) were risk factors significantly associated with subsequent NAFLD occurrence, whereas 2-h insulin level in 75 g glucose tolerance test (GTT) (HR 1.2, 95% CI 0.5–2.5, p = 0.70) and body mass index (BMI) > 25 kg/m2 (HR 2.2, 95% CI 0.6–8.0, p = 0.24) was not. Among NAFLD patients who underwent TE, a higher number of MetS components indicated a worse degree of fibrosis and steatosis. MetS diagnosis and HA at PCOS diagnosis were risk factors associated with NAFLD, while 2-h insulin level in 75 g GTT and obesity were not. Although elevated aspartate aminotransferase levels were significant for NAFLD risk, liver enzyme elevations may not be present until late liver damage. Further prospective studies of PCOS women with MetS or HA are warranted to determine whether patients without liver enzyme elevations should undergo preemptive liver examinations.

Cytokine support of embryonic development includes promotion of implantation and protection of blastomeres from cell stress and apoptosis. Correlations between embryo quality and concentrations of specific cytokines in culture media of human embryos have been investigated for many years. The aim of this study was to assess the concentrations of cytokines in preimplantation embryo culture media and to investigate their relationships with embryo quality and in vitro fertilization (IVF) outcomes. Seventy-two samples were obtained from 39 infertile couples undergoing IVF or intracytoplasmic sperm injection treatment between October 2018 and May 2019. Each embryo was cultured separately, and the embryo culture medium was collected 72 h after fertilization. Before embryo transfer on day 3, a morphological evaluation of each embryo was performed. Cytokine concentrations of each culture medium were analyzed for 23 selected cytokines using the Multiplex Cytokine/Chemokine Panel II Assay (Merck Millipore®). The results were categorized into two groups (top-quality and non-top-quality embryos). The median age of the 39 patients was 34 years. Nine of 23 cytokines were quantified and compared between the top-quality embryo group and non-top-quality embryo group. Among the nine cytokines, CCL15, CCL27, and CXCL-12 were significantly elevated in the top-quality embryo group. These results suggested that specific cytokines measured in human embryo culture media can be used to predict embryo quality and IVF outcomes.

This study was performed to evaluate the long-term cardiovascular safety of gemigliptin in patients with type 2 diabetes mellitus (T2DM). After screening, eligible patients with T2DM were enrolled, received gemigliptin, and were followed up for a median of 2.50 years. The primary outcome was a composite of confirmed cardiovascular death, nonfatal myocardial infarction, or nonfatal ischemic stroke (3-point major adverse cardiovascular event [MACE]). The key secondary outcomes were incidence of all-cause mortality and any other cardiovascular events. A total of 5179 patients were included in the study and 5113 were treated with gemigliptin. Overall, the primary outcome occurred in 26 patients within 12 months (estimated incidence by Cox proportional hazard model 0.49%, 95% CI 0.29–0.69%) and in 54 patients within 54 months (estimated incidence from Cox proportional hazard model 1.35%, 95% CI 0.92–1.77%). During the study period, the incidence rates of each component of the primary composite outcome were 0.04% (0.2 events per 1000 person-years) for cardiovascular death, 0.51% (2.2 events per 1000 person-years) for nonfatal myocardial infarction, and 0.61% (2.5 events per 1000 person-years) for nonfatal ischemic stroke. The incidence of all-cause mortality was 0.82% (3.2 events per 1000 person-years) and the incidences of other cardiovascular events were all less than 0.3%. In conclusion, T2DM patients who received gemigliptin exhibited a low incidence of the primary composite MACE and all-cause mortality. Therefore, the use of gemigliptin is expected to be safe without an increase in cardiovascular risk.Trial registration: The study was registered at ClinicalTrials.gov (identifier: NCT02290301).

Objective: To evaluate the effect of female sex hormones on the clinical outcomes of coronavirus disease 2019 patients using national claims data. Methods: This retrospective cohort study used the Health Insurance Review and Assessment data of 5,061 adult patients with laboratory-confirmed coronavirus disease 2019 in South Korea from January 20 to April 8, 2020. To evaluate the effect of hormone therapy on clinical outcomes among women, subgroup analyses using age-matched case-control data were performed. Results: Coronavirus disease 2019 was most prevalent in women in the 20-39 years age group (1,250 [44.14%]). Men were more likely to receive oxygen therapy (144 [6.46%] vs 131 [4.63%], P = 0.004), be admitted to the intensive care unit (60 [2.69%] vs 53 [1.87%], P = 0.049), and have a longer length of stay after admission to the intensive care unit (19.70 ± 11.80 vs 14.75 ± 9.23, P = 0.016). However, there was no significant difference in the mortality rate (men vs women: 42 [1.88%] vs 42 [1.48%], P = 0.267). In the multivariable Cox analysis, older age and underlying comorbidities, but not sex, were independent risk factors for mortality. Hormone therapy was not significantly associated with clinical outcomes. Conclusions: This study, using nationwide data, suggests that female sex hormones are not associated with the morbidity and clinical outcomes of coronavirus disease 2019 in South Korea.

Cell membrane ion channels have important roles in cell migration during cancer development and metastasis. Although endometriosis is a benign gynecological disease, some migration and invasion characteristics of endometriosis are similar to those of cancer. However, only a few studies have examined cell membrane ion channels and their associations with endometriosis. This study aimed to investigate the effects of these ion channels on development of endometriosis. A total of 39 women who underwent laparoscopic ovarian cyst enucleation were included in the study population. Eutopic endometrium or ectopic endometrium tissues were obtained from each patient based on allocation to an endometriosis group (n=21) or a control group (n=18). Quantitative real-time PCR (qRT-PCR) and western blot analyses were performed to quantify NKCC1, NKCC2, and CLCN3 mRNA expression and protein concentrations. SiRNA transfection and migration assays of the endometrial stromal cells were performed to test the effects of the ion channels on the migration ability. The qRT-PCR and western blot analyses revealed significantly elevated mRNA expression and protein expression of NKCC1, NKCC2, and CLCN3 in the ectopic endometrial tissue from the patients with endometriosis (p < 0.05). Migration assay of siRNA transfected cells suggested a decreased migratory potential of the endometrial stromal cells (p < 0.001). The magnitudes of expression of NKCC1, NKCC2, and CLCN3 were positively correlated with endometrioma size. The increased expression of NKCC1, NKCC2, and CLCN3 in endometriosis offers opportunities to understand mechanisms of endometriosis and develop novel therapeutic approaches.

Engineered ovary mimetics enable hormone autocrination and restore ovarian functions with reduction of menopause risks., The regeneration potential of implantable organ model hydrogels is applied to treat a loss of ovarian endocrine function in women experiencing menopause and/or cancer therapy. A rat ovariectomy model is used to harvest autologous ovary cells while subsequently producing a layer-by-layer form of follicle spheroids. Implantation of a microchannel network hydrogel with cell spheroids [vascularized hydrogel with ovarian spheroids (VHOS)] into an ischemic hindlimb of ovariectomized rats significantly aids the recovery of endocrine function with hormone release, leading to full endometrium regeneration. The VHOS implantation effectively suppresses the side effects observed with synthetic hormone treatment (i.e., tissue overgrowth, hyperplasia, cancer progression, deep vein thrombosis) to the normal levels, while effectively preventing the representative aftereffects of menopause (i.e., gaining fatty weight, inducing osteoporosis). These results highlight the unprecedented therapeutic potential of an implantable VHOS against menopause and suggest that it may be used as an alternative approach to standard hormone therapy.

It is controversial as to whether papillary thyroid microcarcinoma (PTMC) has some genomic and transcriptomic characteristics that differentiate between an early-stage lesion that would eventually evolve into the larger papillary thyroid cancer (PTC), and an occult indolent cancer in itself. To investigate this, we comprehensively elucidated the genomic and transcriptomic landscapes of PTMCs of different sizes, using a large-scaled database. This study included 3435 PTCs, 1985 of which were PTMCs. We performed targeted next-generation sequencing for 221 PTCs and integrated these data with the data including The Cancer Genome Atlas (TCGA) project. The frequency of v-raf murine sarcoma viral oncogene homolog B (BRAF)V600E mutation was higher in PTMCs &gt, 0.5 cm than that in very small PTMCs (&le, 0.5 cm) and decreased again in PTCs &gt, 2 cm. Among PTMCs, the prevalence of mutations in rat sarcoma (RAS) and telomerase reverse transcriptase (TERT) promoter was not significantly different according to their size, but lower than in large PTCs. There was no change in the tumor mutational burden, the number of driver mutations, and transcriptomic profiles with tumor size, among PTMCs and all PTCs. Although a few genes with differential expression and TERT promoter mutations were found in a few PTMCs, our findings showed that there were no useful genomic or transcriptomic characteristics for the prediction of the future progression of PTMC.

Objectives Iodine deficiency causes multiple health problems. Previously we reported that 96% of high school students in Tuguegarao, Philippines had adequate iodine levels. However, iodine deficiency-associated problems remain among adults in the Philippines. Therefore, we evaluated iodine nutritional status and goiter prevalence among adults, including pregnant women, in Tuguegarao, Philippines. Methods A total of 245 adults, including 31 pregnant women, provided samples for urinary iodine analysis, and all pregnant women completed a questionnaire about iodine deficiency. Results The median urinary iodine level was 164.0 ± 138.4 g/L; 38.4% of the participants were iodine deficient, according to the International Council for Control of Iodine Deficiency Disorders (ICCIDD) criteria. No severe iodine deficiency was observed. Among the 31 pregnant women, 24 (77.5%) fell into the iodine deficient category defined by a stricter World Health Organization (WHO) guideline, in which iodine deficiency is considered when urinary iodine levels are below 150 g/L. Almost half (42%) of the pregnant women were unaware of the harmful effects of iodine deficiency on the human body and their fetus. Conclusions Although iodine nutritional status in the Philippines has improved, iodine deficiency still exists among adults, especially among pregnant women. Therefore, our study strongly suggests that a better strategy should be established to monitor iodine nutritional status among adults continually, and to focus on populations susceptible to iodine deficiency, including pregnant women and women of reproductive age, to achieve the total elimination of iodine deficiency.

Objectives Ultrasound-guided fine-needle aspiration (FNA) is routinely used in the evaluation of thyroid nodules. However, it has several pitfalls, as has been noted in nondiagnostic and indeterminate cases. This study aims to investigate the value of BRAF V600E mutation co-testing in FNA cytology. Method A total of 310 patients underwent BRAF V600E mutation co-testing in FNA cytology on thyroid nodules between June 2013 and June 2014. Of the 310 patients, 69 patients who had undergone a surgery for thyroid nodules were included in this study. The presence of the BRAF V600E mutation was determined by allele-specific polymerase chain reaction amplification of exon 15 of the BRAF gene. Results Of 69 cases, 33 (47.8%) were BRAF V600E mutation positive. The BRAF V600E mutation was not significantly associated with high-risk features such as tumor size, lymph node metastasis, and pathological stage. The respective diagnostic performance of FNA ( P = 0.02), BRAF V600E mutation ( P = 0.03), and ultrasonographic ( P = 0.00) findings was statistically significant. The sensitivity, specificity and positive predictive value of FNA was 64.9%, 83.3%, and 94.8%. The sensitivity, specificity and positive predictive value of BRAF V600E mutation was 56.1%, 91.7%, and 96.9% and the US features was 91.2%, 91.7%, and 98.1% respectively. However, sensitivity of FNA with BRAF V600E mutation (77.2%) was lower than FNA with US (92.9%) and combination all together (92.9%). Conclusion In this study, we found that US features were the most useful in preoperative differential diagnosis of thyroid nodules. BRAF V600E mutation co-testing in FNA cytology was also useful for diagnosis of thyroid tumors.

The aim of this study was to evaluate the effectiveness of postoperative levonorgestrel-releasing intrauterine system (LNG-IUS) insertion after gonadotropin-releasing hormone agonist (GnRH-a) treatment for preventing endometriotic cyst recurrence. The LNG-IUS was applied to 28 women who had undergone surgery for endometriosis followed by 6 cycles of GnRH-a treatment. Clinical characteristics, endometriosis recurrence, and adverse effects were analyzed. Student t test was performed for analysis. Before surgery, 20 (71.4%) patients had dysmenorrhea, and the mean pain score (visual analog scale [VAS]) was 4.26. The numbers of women diagnosed with stage III endometriosis and stage IV endometriosis were 15 (53.6%) and 13 (46.4%), respectively, according to the revised American Fertility Society scoring system. The mean cancer antigen 125 levels and VAS scores were significantly lower after treatment than before treatment (11.61 vs 75.66 U/mL, P

This research aimed to evaluate the potential therapeutic effects of Rg3 on endometriosis and identify target miRNAs. We designed an in vitro study using human endometrial stromal cells (HESCs) obtained from patients with endometriosis and an in vivo study using mouse models. HESCs were treated with Rg3-enhanced red ginseng extract (Rg3E); real-time PCR and microarray profiling, transfection, and western blot were performed. Mouse endometriosis models were developed and supplemented with Rg3E for 8 weeks. Gross lesion size and fibrotic character were analyzed in the mouse models. RNA levels of Ki-67, col-1, CTGF, fibronectin, TGF-β1, MMP2 and MMP9 significantly decreased in HESCs after Rg3E treatment. Microarray analysis revealed downregulation of miR-27b-3p, which is related to fibrosis modulation. Expression of miR-27b-3p was significantly higher in HESCs from patients with endometriosis than that of controls, and Rg3E treatment significantly decreased its expression; the contraction and migration assay revealed significant reductions in both fibrosis and migration potential in Rg3E-treated HESCs from endometriosis patients. A decrease in size and fibrotic character of endometrial lesions from the Rg3E groups was observed in vivo. In conclusion, Rg3 effectively altered fibrotic properties of HESCs from patients with endometriosis, which is likely associated with miR-27b-3p modulation.

Sarcopenia and insulin resistance are common co-morbidities in the elderly and are known to be associated with vitamin D deficiency. However, no previous studies have investigated interactions between all three of these factors. We aimed to investigate the relationship between 25-hydroxyvitamin D concentration, sarcopenia, and insulin resistance in postmenopausal Korean women.This study used data from the Korea National Health and Nutrition Examination Survey 2008-2011. Participants were 3744 postmenopausal Korean women. Sarcopenia was defined as appendicular skeletal muscle mass divided by body weight1 standard deviation below the mean for women aged 20-40 years. The serum 25-hydroxyvitamin D and fasting insulin levels were measured, and insulin resistance was calculated using the formula: fasting plasma glucose (mg/dl) × fasting insulin (mIU/l)/405.We found a strong inverse association between 25-hydroxyvitamin D concentration and sarcopenia in postmenopausal Korean women (p = 0.0009). There was also a significant association between sarcopenia and insulin resistance, independent of vitamin D and obesity status (p 0.0001). However, there was no significant association between 25-hydroxyvitamin D concentration and insulin resistance. In the subgroup analysis, insulin resistance was found to be determined by sarcopenic rather than vitamin D status.Sarcopenia was associated with both insulin resistance and 25-hydroxyvitamin D concentration in postmenopausal Korean women, regardless of obesity status. However, 25-hydroxyvitamin D concentration was not associated with insulin resistance. Sarcopenia is therefore of greater clinical importance due to its close relationship with insulin resistance.

s Background Although previous studies have established a close relationship between caloric intake and metabolic syndrome, there is limited research exploring the impact of meal frequency adjusted by caloric intake on metabolic syndrome (MetS). Objective To evaluate the association of meal frequency and MetS after adjusting for confounding factors including caloric intake in Korean men and women. Methods We analyzed the national representative data of a total 12,389 adults (5171 men, 7218 women) from the Korean National Health and Nutrition Examination Survey (KNHANES) 2010–2012. Subjects were categorized as eating 3 meals/day (MF3) or 2 or fewer meals/day (MF ≤ 2). Daily caloric intake was calculated using CAN-Pro 4.0 (The Korean Nutrition Society, Seoul, Korea). Results The prevalence of components of MetS differed significantly according to meal frequency in both men and women. In an unadjusted analysis, the prevalence of MetS in women was significantly higher in the MF3 group than the MF ≤ 2 group (27.5% vs. 17.8%, P

The aim of this study was to evaluate the differences in mortality among colon cancer patients with or without diabetes and to determine optimal glycemic target level for colon cancer patients with diabetes.A total of 741 patients with colon cancer between April 1999 and December 2010 were reviewed. The non-diabetes group had a fasting plasma glucose126mg/dL, and the diabetes group had a fasting plasma glucose ⩾126mg/dL. Patients with diabetes were further divided based on glycemic control into either the uncontrolled subgroup (HbA1c ⩾8%) or the well-controlled subgroup (HbA1c8%).Patients with diabetes had significantly shorter overall survival and median survival than non-diabetes patients. Uncontrolled diabetes patients had significantly shorter overall survival and median survival than well-controlled diabetes patients. The relative risk of mortality for diabetes patients was higher than non-diabetes patients (relative risk 1.17). The relative risk of mortality in uncontrolled diabetes patients was significantly higher than in well-controlled diabetes patients (relative risk 4.58). The area under the curve for mortality and HbA1c level was 0.73. The cut off HbA1c level was 7.75%.A optimal glycemic control level for colon cancer patients with diabetes should be recommended as an HbA1c of 7.8% or below.

Objectives With the rapid increase in the prevalence of diabetes, the age groups of diabetic patients are becoming diversified. This study will examine the degree of obesity, insulin resistance, and insulin secretion ability among patients first diagnosed with diabetes according to age and gender. Methods The subjects of this study included 616 patients who were first diagnosed with diabetes during a routine physical examination. This sample was obtained from a total of 28,075 adults aged 19 years and older who received the examination among 33,829 participants in the Korea National Health & Nutrition Examination Survey (KNHANES) from 2007–2010. The subjects were categorized by age into young age (age: 19 – 39 years), middle age (age: 40 – 59 years), and old age (age: 60 years and older). The degree of obesity was categorized according to body mass index (BMI) into normal weight (BMI: 18.5 ∼ 22.9), overweight (BMI: 23 ∼ 24.9), and obesity (BMI: 25 or above). Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR). Results It was found that 14.1% (n = 87) of a total of 616 subjects (324 men, 292 women) were in the young age group, 43.8% (n = 270) were in the middle age group, and 42.1% (n = 259) were in the old age group. In addition, 83.3% of men that were overweight or obesity were in the young age group, while 79.2% and 60.5% were in the middle age and old age groups, respectively. A total of 82.2% of women that were overweight or obesity were in the young age group, while 79.5% and 77% were in the middle age and old age groups, respectively. For men, the more obesity they were in all age groups, the higher their HOMA-IR. For women, the more obesity they were in the young age and middle age groups, the higher their HOMA-IR; however, women in the old age group showed the highest HOMA-IR when they were of normal weight. Conclusion Among diabetic patients first diagnosed with the disease in Korea, the youth population had the highest obesity rate. Insulin resistance increases as an individual's weight increases among those patients who are first diagnosed with diabetes; the only exception noted is for elderly women.

hMSC source-specific behaviors in 3D NO gel represent EC-like differentiation of ADSCs and pericyte-like characteristics of BMSCs., Angiogenesis is stimulated by nitric oxide (NO) production in endothelial cells (ECs). Although proangiogenic actions of human mesenchymal stem cells (hMSCs) have been extensively studied, the mechanistic role of NO in this action remains obscure. Here, we used a gelatin hydrogel that releases NO upon crosslinking by a transglutaminase reaction (“NO gel”). Then, the source-specific behaviors of bone marrow versus adipose tissue-derived hMSCs (BMSCs versus ADSCs) were monitored in the NO gels. NO inhibition resulted in significant decreases in their angiogenic activities. The NO gel induced pericyte-like characteristics in BMSCs in contrast to EC differentiation in ADSCs, as evidenced by tube stabilization versus tube formation, 3D colocalization versus 2D coformation with EC tube networks, pericyte-like wound healing versus EC-like vasculogenesis in gel plugs, and pericyte versus EC marker production. These results provide previously unidentified insights into the effects of NO in regulating hMSC source-specific angiogenic mechanisms and their therapeutic applications.

Estrogen affects endometrial cellular proliferation by regulating the expression of the c-myc gene. B-cell translocation gene 1 (BTG1), a translocation partner of the c-myc, is a tumor suppressor gene that promotes apoptosis and negatively regulates cellular proliferation and cell-to-cell adhesion. The aim of this study was to determine the role of BTG1 in the pathogenesis of endometriosis. BTG1 mRNA and protein expression was evaluated in eutopic and ectopic endometrium of 30 patients with endometriosis (endometriosis group), and in eutopic endometrium of 22 patients without endometriosis (control group). The effect of BTG1 downregulation on cellular migration, proliferation, and apoptosis was evaluated using transfection of primarily cultured human endometrial stromal cells (HESCs) with BTG1 siRNA. BTG1 mRNA expression level of eutopic and ectopic endometrium of endometriosis group were significantly lower than that of the eutopic endometrium of the control group. Migration and wound healing assays revealed that BTG1 downregulation resulted in a significant increase in migration potential of HESCs, characterized by increased expression of matrix metalloproteinase 2 (MMP2) and MMP9. Downregulation of BTG1 in HESCs significantly reduced Caspase 3 expression, indicating a decrease in apoptotic potential. In conclusion, our data suggest that downregulation of BTG1 plays an important role in the pathogenesis of endometriosis.

Background: There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of piogli tazone or glimepiride when added to metformin plus alogliptin treatment for T2DM. Methods: This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investi gator’s judgement. Results: Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pio glitazone: -0.81%, P