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Discovering new drugs is an expensive and time-consuming process, including target identification, bioavailability, pharmacokinetic (PK) tests, pharmacodynamic (PD) tests, toxicity profiles, recommended dosage test, and observation of the side effects, etc. Repurposed drugs could bypass some steps, starting from phase II trials, and shorten the processes. Statins, also known as HMG-CoA inhibitors (HMGCR), are commonly used to manage and prevent various cardiovascular diseases and have been shown to improve the morbidity and mortality of patients. In addition to the inhibitory effects on the production of cholesterol, the beneficial effects of statins on the prognosis and risk of various cancers are also shown. Statins not only inhibited cell proliferation, metastasis, and chemoresistance but affected the tumor microenvironment (TME). Thus, statins have great potential to be repurposed in oncology. Hence, we review the meta-analysis, cohort, and case-control studies of statins in gynecological cancers, and elucidate how statins regulate cell proliferation, apoptosis, tumor growth, and metastasis. Although the results in gynecological cancers remain controversial and the effects of different statins in different histotypes of gynecological cancers and TME are needed to elucidate further, statins are excellent candidates and worthy of being repurposed drugs in treating gynecological cancers.

Ovarian cancer is one of the most lethal gynecological cancers, and 80% are high-grade serous carcinomas (HGSOC). Despite advances in chemotherapy and the development of targeted therapies, the survival rate of HGSOC has only moderately improved. Therefore, a cell model that reflects the pathogenesis and clinical characteristics of this disease is urgently needed. We previously developed a human fallopian tube epithelial cell line (FE25) with p53 and Rb deficiencies. After long-term culture in vitro, cells at high-passage numbers showed spontaneous transformation (FE25L). This study aimed to compare FE25 cells cultured in vitro for low (passage 16–31) and high passages (passage 116–139) to determine whether these cells can serve as an ideal cell model of HGSOC. Compared to the cells at low passage, FE25L cells showed increased cell proliferation, clonogenicity, polyploidy, aneuploidy, cell migration, and invasion. They also showed more resistance to chemotherapy and the ability to grow tumors in xenografts. RNA-seq data also showed upregulation of hypoxia, epithelial-mesenchymal transition (EMT), and the NF-κB pathway in FE25L compared to FE25 cells. qRT-PCR confirmed the upregulation of EMT, cytokines, NF-κB, c-Myc, and the Wnt/β-catenin pathway. Cross-platform comparability found that FE25L cells could be grouped with the other most likely HGSOC lines, such as TYKNU and COV362. In conclusion, FE25L cells showed more aggressive malignant behavior than FE25 cells and hence might serve as a more suitable model for HGSOC research.

Opportunistic salpingectomies (OSs) are concurrently performed with hysterectomies to prevent epithelial ovarian cancer. This study aimed to investigate the correlation between OS and early menopause in females who have undergone hysterectomies. This was a retrospective cohort study involving 79 females who had undergone a hysterectomy, with or without an OS, between January 2007 and December 2015. Their ages at surgery, at menopause, and the lengths of time from surgery to menopause were compared. An OS had been performed in 54 and not performed in 25 of the enrolled patients, comprising the OS and non-OS groups. Body mass index was significantly higher in the OS group (OS: 25.27 ± 4.17 vs. non-OS: 22.97 ± 3.27, p = 0.01). Additionally, menopausal sleep problems were more prevalent in the OS group than in the non-OS group (41% vs. 12%, p = 0.01). Notably, the time from surgery to menopause was significantly shorter in the OS group than in the non-OS group (OS: 1.84 ± 1.85 vs. non-OS: 2.93 ± 2.43, p = 0.031). After adjusting the covariates, the OS group was associated with a significantly shorter period between surgery and menopause (p = 0.029). In conclusion, these results showed that a hysterectomy plus an OS might cause earlier menopause than a hysterectomy only. An OS should be preoperatively discussed with patients regarding the possibility of early menopause. The findings of this study require further large-scale investigations to reinforce the results.

Background: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. Methods: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylation status of two genes (BHLHE22, CDO1) and combined with two other clinical variables (age, BMI). The cutoff threshold of the MPap value was established in stage 1 and validated in stage 2. A total of 592 women with abnormal uterine bleeding were enrolled from five medical centers throughout Taiwan. Results: In stage 1, the sensitivity, specificity, and positive and negative predictive values of the MPap test for detecting endometrial cancer were 92.9%, 71.5%, 39.8%, and 98.0%, respectively. These values were validated in stage 2, being 92.5%, 73.8%, 40.2%, and 98.1%. Moreover, MPap outperformed transvaginal ultrasound in sensitivity and negative predictive values for detecting endometrial cancer. When we applied the algorithm for triage of endometrial cancer detection by MPap in the Taiwan National Health Insurance dataset, we found that it may reduce invasive procedures by 69~73%. Conclusions: MPap may provide a feasible alternative for endometrial cancer detection and can be considered as a triage test to reduce unnecessary invasive procedures.

High-grade serous ovarian cancer (HGSOC) constitutes 80% of ovarian cancer. Cancer stem cells (CSCs) are responsible for most of the tumor metastasis and chemoresistance. n-Butylidenephthalide (BP) is a potential anti-tumor agent for treating a variety of cancers. The aim of this study was to evaluate the effect of BP on CSCs of HGSOC. CSCs were isolated using the CSC marker (ALDH; aldehyde dehydrogenase) from KURAMOCHI and OVSAHO cells (HGSOC cell lines). The cell proliferation, IC50 (the half-maximal inhibitory concentration), cell migration and invasion, TUNEL (terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling) assay, western blot of ovarian CSC were evaluated. The animal xenograft studies were evaluated on an immunodeficient mouse model. The results showed the proliferation of ALDH+ cells was greater than that of ALDH- cells. The dosage of IC50 of BP was higher in ALDH+ cells than in mixed cancer cells (317.2 vs. 206.5 μg/ml) in KURAMOCHI cells, but not in OVSAHO cells (61.1 vs. 48.5 μg/ml). BP could inhibit the migration and invasion of both cancer stem cells. BP treatment could activate apoptosis signaling, as indicated by the TUNEL assay and the increased expression of cleaved caspase-3, -7, and -9 but not cleaved caspase-8. A low dose of BP (20 and 25 μg/mL) treatment could increase the toxicity of taxol and cisplatin. In the animal model, BP (200 mg/kg) treatment also decreased the KURAMOCHI and OVSAHO tumor growth rate and induced tumor apoptosis. In conclusion, BP could kill ALDH+ CSCs of HGSOC in vitro and in vivo by inducing apoptosis. BP may provide a new therapeutic approach for HGSOC.

Two to five percent of infants and children experience febrile seizures (FS). Breastfeeding is beneficial to the health of mothers and children. Nevertheless, the benefits of breastfeeding in reducing FS remain unclear; thus, the present study aimed to evaluate this association. The case group was selected from 2010 to 2019, and the selected population was children younger than 5 years (i.e., children born from 2005–2019). The control group was selected from newborn infants at our hospital born between 2005 and 2019. Finally, 55 children with FS and 110 children in the control group were recruited. The results show longer breastfeeding duration is associated with an increased risk of FS (adjusted odds ratio: 1.06, 95% confidence interval: 1.01–1.11, p = 0.028). When comparing cases of FS with the control group, the percentage of inclusive breastfeeding over 12 months (32.7% vs. 9.1%, p = 0.017) and longer duration of exclusive breastfeeding were higher (10.86 ± 11.82 vs. 5.40 ± 7.17 months, p < 0.001). However, the comparison of the prevalence of FS between the different breastfeeding duration groups did not reach statistical significance. In conclusion, our study showed that a longer breastfeeding duration was associated with a higher risk of FS. Future large-scale studies evaluating the association between breastfeeding duration and febrile seizures are needed.

Objective To present a case of vulvar myoma and the factors differentiating this tumor from Bartholin's cyst. Case report A 50-year-old woman presented with a nodule over the left labia majora. Pelvic examination showed swelling and redness of the left labia majora. A 2-cm nodule with firm consistency was found near the vaginal opening. There was no inguinal lymphadenopathy. Bartholin's cyst was suggested, and oral cephalexin was prescribed for 1 week, but no improvement was seen. Therefore, she underwent excision of the nodule. Pathology revealed it to be a benign vulvar myoma. The patient recovered well, and no recurrence was noted after 2 months of follow-up. Conclusion Vulvar myoma is rare. Sexual history, nodule consistency, and imaging are helpful, but the final diagnosis of vulvar myoma is usually made following surgical excision and histopathological analysis.

Objective The aim of the study was to propose a method using saline lubrication and two glass slides to reduce the proportion of inadequate Pap smears. Materials and methods This was a retrospective study of patients at a medical center in eastern Taiwan that performs 5000–6000 Pap smears annually. The extracted data only detailed the number and percentage of inadequate Pap smears. We applied two modifications to the conventional Pap smear technique. The first modification was lubricating the speculum with normal saline instead of jelly. The second modification was performing the smear on two glass slides instead of just one. We used the modified technique beginning in January 2017. Therefore, we collected data from 2016 (before the modified technique was employed) and 2018 (after the modified technique was employed). The categorical data are presented as numbers (percentages). The differences in the number and percentage of inadequate smears resulting from both techniques were assessed using the Chi-square test. Results During 2016 and 2018, 28 and 2 women received inadequate Pap smears among the total of 594 and 613 women who received Pap smears, respectively. The proportion of inadequate Pap smears was 4.71% and 0.33% in 2016 and 2018, respectively (P Conclusions The use of this modified technique effectively reduced the percentage of inadequate Pap smears.

This study aimed to evaluate fetal adverse outcomes of laparoscopy and laparotomy in pregnant women to determine the safety of these surgical approaches. This was a retrospective nationwide case–control study of women who became pregnant for the first time between 2000 and 2012 in Taiwan. The case (with adverse fetal outcomes) and control groups comprised 208,604 and 417,124 participants, respectively. Participants who underwent appendectomy, cholecystectomy, ovarian cystectomy, or myomectomy were treated with either laparoscopy or laparotomy. A conditional logistic regression model was used to calculate the odds ratios (ORs) for adverse fetal outcomes. The laparotomy and laparoscopy groups comprised 632 and 536 patients, respectively. Women who underwent laparoscopy had a significantly higher risk of adverse fetal outcomes (adjusted OR [AOR] = 2.33; 95% CI 1.66–2.99) than those who underwent laparotomy. Adverse fetal outcomes were found to be significantly associated with laparoscopy among women aged 20–39 years (AOR = 2.30; 95% CI 1.70–3.31). Regarding surgical indication, unlike laparotomy, laparoscopic cholecystectomy and appendectomy were not associated with adverse fetal outcomes. However, laparoscopic myomectomy and ovarian surgeries were associated with a higher incidence of adverse fetal outcomes than the laparotomy group (AOR = 2.29 [95% CI 1.57–3.35, p

Transplantation of chondrogenic stem cells is a promising strategy for cartilage repair, but requires improvements in cell sourcing, maintenance, and chondrogenic differentiation efficiency. We examined whether gelatin honeycomb scaffolds can enhance the proliferation, viability, and chondrogenic capability of human umbilical cord mesenchymal stem cells (HUCMSCs) compared to standard plate cultures. In addition, the survival and phenotypic stability of HUCMSC-derived chondrocytes in a scaffold were evaluated in mice over 6 weeks post-transplantation. Survival and proliferation rates of HUCMSCs were comparable between scaffold and plate culture. Scaffold culture in a chondrogenic differentiation medium induced more stable expression of the key hyaline cartilage genes COL2A1 and ACAN and the production of the respective proteins Type II collagen and aggrecan as well as glycosaminoglycan. These HUCMSC-differentiated chondrocytes also stably expressed cartilage genes and proteins in the scaffold 6 weeks after transplantation into nonobese diabetic/severe combined immunodeficient mice. These findings indicate that honeycomb-like gelatin scaffolds can promote the survival and chondrogenic differentiation of HUCMSCs to form hyaline-like cartilage.

Ovarian diffuse large B-cell lymphoma (DLBCL) is rare. DLBCL is a complex type of lymphoma. The ovarian DLBCL usually harbor a favorable prognosis. We report a case of ovarian DLBCL that presented as an ovarian mass with lower abdominal pain and was managed using laparoscopic staging surgery. A 29-year-old female (gravida 2, para 0, abortion 2) with a history of polycystic ovarian syndrome with irregular medication control visited our clinic due to lower abdominal pain. Transvaginal ultrasound revealed a heterogeneous, septated mass over the left adnexa with a diameter of approximately 6 cm × 8 cm. The tumor marker CA 19-9 was elevated (65.77 IU/mL); CA125 and carcinoembryonic antigen were not elevated. Laparoscopic surgery with left salpingo-oophorectomy was first performed. Frozen section indicated dysgerminoma. Then, we continued staging surgery through bilateral pelvic lymph node dissection, para-aortic lymph node dissection, omentectomy, right ovary and peritoneum biopsy, and washing cytology. Ovarian tumor and para-aortic lymph nodes were positive for lymphoma. The tumor cells were positive staining for CD20, CD5, ki67, BCL-6, and MUM-1, which was associated with DLBCL. The patient was then consulted for oocyte preservation and referred to hematology for further chemotherapy. In conclusion, an ovarian lymphoma is a rare event. The presence of an enlarged ovarian tumor should raise the suspicion of ovarian lymphoma. To differentiate ovarian lymphoma from dysgerminoma, immunohistochemistry is useful. Fertility preservation should be considered before chemotherapy. Ovarian tissue or oocyte preservation or gonadotropin-releasing hormone agonist injection before chemotherapy can be performed for fertility preservation.

We aim to evaluate breast cancer risk relating to PPIs usage in women with peptic ulcer. From 2000 to 2013, incidence rates of breast cancer were compared between the two cohorts (with or without PPIs). Each study cohort consisted of 4838 women. The incidence density rate of breast cancer in the PPI cohort was 0.29 that in the comparison cohort (10.0 vs 31.6 per 10 000 person-years), with an adjusted HR (hazard ratio) of 0.32 (95% CI = 0.20-0.49) for the PPI cohort. In conclusion, the medication of PPIs is associated with reduced breast cancer risk for women with gastric ulcer.

Background Fallopian tube epithelial cells (FTEC) were thought to be the origin of high-grade serous ovarian carcinoma (HGSOC). Knowledge of the stemness or initiating characteristics of FTEC is insufficient. Previously, we have characterized the stemness cell marker of FTEC, this study aims to further characterize the clonogenicity and spheroid features of FTEC. Methods We successfully derived FTECs from the epithelial layer of the human fallopian tubes. We examined the morphology, proliferation rate, doubling time, and clonal growth of them. At passage 3, the sphere formations on gelatin-coated culture, suspension culture, and matrigel culture were observed, and the expression of LGR5, SSEA3, SSEA4, and other stemness markers was examined. Furthermore, tissue-reconstituted organoids from coculture of FTEC, fallopian stromal cells (FTMSC) and endothelial cells (HUVEC) were examined. Results FTEC exhibited cuboidal cell morphology and maintained at a constant proliferation rate for up to nine passages (P9). FTEC could proliferate from a single cell with a clonogenic efficiency of 4%. Flow cytometry revealed expressions of normal stem cell markers (SSEA3, SSEA4, and LGR5) and cancer stem cell markers (CD24, CD44, CD117, ROR1, and CD133). FTEC formed spheres and colonies when cultured on low attach dish. In the presence of Matrigel, the stemness and colony formation activity were much enhanced. In co-culturing with FTMSC and HUVEC, FTEC could form organoids that could be blocked by Wnt inhibitor DKK1. Expressions of LGR5 and FOXJ1 expression were also decreased by adding DKK1. Conclusion We demonstrated abundantly presence of stem cells in human FTECs which are efficient in forming colonies, spheres and organoids, relying on Wnt signaling. We also reported for the first time the generation of organoid from reconstitutied cell lineages in the tissue. This may provide a new model for studying the regneration and malignant transformation of the tubal epithelium.

Several studies have shown that menopausal hormone therapy (MHT) reduces the risk of hemorrhagic stroke (HS), but there are no studies comparing the effect of different estrogen types (conjugated equine estrogen [CEE] and estradiol [E2]).This retrospective cohort study included menopausal women aged 40-65 years diagnosed between 2000 and 2016 who received MHT with oral CEE or E2 and were registered in Taiwan's National Health Insurance Research Database. The primary outcome was HS. Propensity score matching with menopausal age and comorbidities was performed. Cox proportional hazard regression models were used to calculate the incidence and hazard ratios (HRs) of HS.A total of 14,586 pairs of women were included. The mean menopausal ages of the CEE and E2 groups were 50.45 ± 5.31 and 50.31 ± 4.99 years, respectively. After adjusting for age and comorbidities, the incidence of HS was 1.23-fold higher in women treated with CEE than in those treated with E2 (8.04 vs. 6.49/10,000 person-years), with an adjusted HR of 1.50 (95 % confidence interval [CI] 1.04-2.17). MHT with CEE initiated within 5 years of menopause was associated with a higher risk of HS than MHT with E2 (HR = 1.47, 95 % CI: 1.01-2.14).In postmenopausal Taiwanese women, MHT with CEE was associated with an increased risk of HS compared to MHT with E2, a risk that women using CEE should discuss with their clinicians. Further large-scale investigations of this population are warranted.

This study aimed to determine whether transvaginal sonographic measurement of cervical length before labor induction can predict successful induction. This retrospective study recruited 138 pregnant women who underwent labor induction at 37–41 weeks of gestation. Cervical length was measured using transvaginal ultrasonography before labor induction. Labor was induced according to the hospital protocol. Age, gestational age (GA), parity, body mass index (BMI), Bishop score, hemoglobin level, maternal disease, and epidural anesthesia were also recorded. Labor induction outcomes, including cesarean section for failed induction, time of induction, and the three labor stages, were assessed. From December 2018 to December 2021, 138 women were recruited for our study, including 120 and 18 women with successful and failed labor induction, respectively. Shorter cervical length (≤3.415 cm, OR = 6.22, 95% CI = 1.75–22.15) and multiparity (OR = 17.69, 95% CI = 2.94–106.51) were associated with successful induction. Higher BMI was associated with failed induction (OR = 0.87, 95% CI = 0.75–0.99). Age, GA, Bishop score, and fetal birth weight were not associated with successful labor induction. The ROC curve showed a cervical length cutoff value of 3.415 cm, revealing 76.8% of the area under the curve. In conclusion, a shorter cervical length (≤3.415 cm) was associated with a higher chance of successful labor induction (76.8%). This parameter might be used to predict the chance of successful labor induction. This information could help better inform clinician discussions with pregnant women concerning the chance of successful labor induction and consequent decision-making. Nevertheless, further large-scale clinical trials are warranted.

To show the technique of reduced sutures in 3D laparoscopic tubal reanastomosis.Step-by-step demonstration of the procedure using video.Laparoscopic tubal sterilization reversal demands high precision and requires both skill and experience. Conventionally, 4 to 6 interrupted patterns using 6-0 to 8-0 absorbable sutures are used for laparoscopic tubal reanastomosis. We used fewer and larger sutures under a magnified 3D view to perform the procedure.We presented a case of a 42-year-old woman, gravida 3, para 3, who underwent tubal sterilization during Cesarean section 10 years ago. Preoperative hysterosalpingography (HSG) showed bilateral distal tubal occlusion. The procedure started with the subserosal injection of diluted vasopressin in both proximal and distal ends and in the mesosalpinx to facilitate dissection and hemostasis. After transection of tubal stump and removal of scar tissue, we used a 3 Fr ureteral catheter as the stent to facilitate suturing. Three interrupted 4-0 monocryl sutures were used for suturing both tubal mucosal and muscular layers at 6, 2, and 10 o'clock sites. We performed bilateral ampullo-ampullary reanastomosis. The tubes were successfully reanastomosed, and patency was confirmed by chromotubation performed at the end of the procedure (Figure 1). The operation lasted for 71 minutes. The operative blood loss was less than 50 ml. Patent right fallopian tube was confirmed on postoperative HSG 1 month later. The patient had a successful pregnancy 8 months after the operation.Our experience shows the feasibility of 3D laparoscopy for tubal reanastomosis using reduced sutures. The technique alleviates the damage to the fallopian tube. The operative time, hospital stay, and postoperative adhesions were significantly lower than the conventional method with a comparable success rate.

Coronavirus disease-2019 (COVID-19) has affected more than 608 million people and has killed 6.5 million people in the world. A few studies showed traditional Chinese medicine can be beneficial for COVID-19 treatment. An herbal preparation Jin Si Herbal Tea (JS) was formulated with herbal extracts known for their potential to decrease spike protein and ACE2 interaction, 3CL, and TRPMSS2 protease activity, and thus aimed to evaluate the clinical course of JS co-treatment along with the usual treatment schedule given for severe COVID-19 patients.This retrospective cohort study included patients with severe COVID-19 admitted to Hualien Tzu Chi Hospital between June and July 2021. All the patients were co-treated with JS and the primary outcome was death. The secondary outcomes included laboratory exam, Ct value, clinical course, and hospital stays. There were 10 patients recruited in this study and divided into 70 years and ≧ 70 years groups (n = 5 in each group).Older patients (≧70 years) had a higher Charlson Comorbidity Index, VACO index, and lower hemoglobin levels than 70 years patients. The trend of lymphocyte count, LDH, D-dimer, and Ct value of non-survivors was not consistent with previous studies. The death rate was 20% and the recovery rate to mild illness in 14 days was 40%.In conclusion, this is the first clinical study of JS co-treatment in severe COVID-19 patients. JS co-treatment might reduce death rate and recovery time. Further large-scale clinical trials would be expected.

Endometriosis is a common systemic chronic inflammatory disease. Inflammation is the key mechanism responsible for the development of endothelial dysfunction and atherosclerosis. We aimed to investigate the risk of coronary artery disease (CAD) among Asian women with endometriosis. This retrospective population-based cohort study included patients with endometriosis diagnosed from 2000 to 2012 and registered in the Longitudinal Health Insurance Database, Taiwan. The comparison cohort (those without endometriosis) were selected (1:4) by matching the age frequency and the index year. We followed up the patients until the diagnosis of CAD (ICD-9-CM codes: 410–414, A270, and A279), withdrawal from the National Health Insurance system, death, or the end of the study. We used a multivariable-adjusted Cox proportional hazard model for evaluating the risk of CAD. We included 19,454 patients with endometriosis and 77,816 women as a comparison group. The mean age of the women at the diagnosis of endometriosis was 37.4 years. A total of 3245 women developed CAD in both groups during a median follow-up of 7 years. The incidence of CAD was higher in women with endometriosis than in those without (5.96 vs. 4.38 per 10,000 person-years, adjusted hazard ratio [95% confidence interval], 1.34 [1.22–1.47]). In conclusion, Asian women with endometriosis had a significantly higher risk of CAD. Further large-scale studies are needed to elucidate the cause-effect relationship between endometriosis and CAD.

Pelvic inflammatory disease (PID) affects 4.4% of women aged 18−44 in the United States, and may cause infertility if it is ineffectively treated. A combination of clindamycin and gentamicin is generally used for the treatment of PID. The benefit of adding metronidazole into the treatment combination still remains unclear, and this study was designed to evaluate its effectiveness. We retrospectively included 107 women who were diagnosed with PID from May 2013 to September 2020 in a single hospital. Based on their used antibiotic regimens, the patients were divided into three groups—those who were treated with clindamycin + gentamicin (group 1, n = 46), those who took regular antibiotics plus metronidazole (group 2, n = 27), and others (group 3, n = 34). Primary outcomes included the rates of taking surgery after failed antibiotics, occurrence/rupture of tubo-ovarian abscesses, and readmission within the following 6 months of first treatment. Secondary outcomes to assess were the length of stay (LOS) and expenditure for PID. There were no significant differences in the surgical rates, readmission rates, LOS and expenditure noted between the three groups. Subgroup analysis showed that visual analogue pain scores being 5 or more would increase the LOS by 3.83 days (p &lt, 0.001), and body temperature &gt, 38.3 °C or more would increase the treatment total expenditure (p &lt, 0.001). Our study results suggest that the combination of clindamycin + gentamicin is a convincible treatment protocol for PID.

Seprafilm becomes brittle and sticky after contact with water, rendering it difficult to use in laparoscopic surgery. Hence, Seprafilm is not used frequently in laparoscopic surgery. This prospective randomized controlled trial aimed to compare the feasibility of two methods of application of Seprafilm: wet and non-wet. Two groups comprised 30 patients, each with 180 pieces of Seprafilm. Symptomatic patients who underwent laparoscopic surgeries, including hysterectomy and adnexal surgeries, were recruited. Successful application of Seprafilm was defined as a smooth attachment to the site of application. Sticky and fractured Seprafilm sheets were defined as failed applications. Between March 2016 and December 2017, 60 patients underwent laparoscopic Seprafilm placement. The preparation time was 32.67 ± 16.63 and 79.50 ± 22.01 s in the non-wet and wet groups, respectively (p &lt, 0.00). The success rate of application was 95.4% in the non-wet group and 98.3% in the wet group (p = 0.09). Placement time was 599.50 ± 90.18 s and 592.53 ± 105.82 s in the non-wet and wet groups, respectively (p = 0.25). In conclusion, the wet and non-wet application methods of Seprafilm were feasible in laparoscopic surgeries. The preparation time was different between the two groups. However, the rate of successful application and placement time was not different between the two groups.

Fallopian tube epithelial cells (FTECs) are thought to be the origin of epithelial ovarian cancer. However, the effect of the hormones on FTECs is unknown, and therefore, this study explored this effect. We successfully derived FTECs from the fallopian tube epithelial layer and treated them with estradiol and progesterone. Reverse transcription polymerase chain reaction was used to evaluate the gene expression of the FTECs' hormone receptors. Confocal and electron microscopy were used to evaluate the morphology of the FTECs after they were treated with hormones. Finally, quantitative PCR was used to evaluate the gene expression of the hormone-treated FTECs. The results showed that the FTECs exhibited cuboidal cell morphology and could be maintained at a constant proliferation rate. Furthermore, flow cytometry revealed that the FTECs expressed stem cell markers, such as SSEA3, SSEA4, and Lgr5. Moreover, the FTECs could express both estrogen and progesterone receptors. In a culture treated with 400 nM estrogen, the FTECs differentiated toward ciliated cells, whereas in a culture treated with estradiol or progesterone, the FTECs increased their expression of certain stem cell markers (SSEA3, SSEA4, and Aldh1) and stemness genes [Wnt (AXIN2, LGR5, LGR6, and OLFM4) and Notch (Hes1) signaling]. In conclusion, hormones may alter the gene expressions of FTECs, and these cells may provide new insights into how FTECs regenerate in response to hormones.

BACKGROUND Hormonal fluctuations may trigger the onset of bipolar disorder. We designed a longitudinal follow-up study to evaluate the association between hysterectomies and bipolar disorder risk. METHODS We conducted a large retrospective cohort study using Taiwan's National Health Insurance Research Database. A total of 4,337 women aged 30 to 50 years who underwent the hysterectomy during 2000-2013 were selected and 17,348 patients without hysterectomy were selected for comparison (1:4 match). Poisson regression analysis was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI). RESULTS During the follow-up of 7.93 years, 20 participants with hysterectomy and 28 without hysterectomy developed bipolar disorder. Receiving hysterectomy was associated with the risk of developing bipolar disorder (adjusted IRR = 2.80; 95% CI = 2.54-3.09). Women with hysterectomy had a higher risk of bipolar disorder in follow-up durations of

The aim of this study was to compare the clinical outcomes of transvaginal mesh (TVM) surgery with and without midline fascial plication for anterior prolapse repair. This is a prospective randomized trial in a teaching hospital. This study compared patients with anterior vaginal wall prolapse (POP-Q Ba &gt, −1) who were randomly assigned to either transvaginal mesh (TVM, Avaulta SoloTM, CR Bard. Inc., Covington, GA, USA polypropylene mesh delivery system) (group A, n = 32) or TVM with concomitant midline fascial plication (group B, n = 32). The outcomes of anatomy correction and life quality were evaluated using a pelvic organ prolapse quantification system and questionnaires. Sixty-four patients were included from January 2011 through April 2014 in this study. Group A had a mean age of 63.7 years and a body mass index (BMI) of 25.4 kg/m2. Group B had a mean age of 62.9 years and a BMI of 25.4. The mean follow-up duration was 18.6 months (range 12–50). At the 12-month follow-up, anatomic recurrence was higher in Group A (5/31, 16.1%) than in Group B (1/30, 3.3%) but without statistical significance (p = 0.19). Improvements in symptoms and quality of life were not significantly different between the two groups. Mesh extrusion was detected in three of 61 patients (4.9%): two from group A (6.7%) and one from Group B (3.2%). TVM with concomitant midline fascia repair for anterior vaginal prolapse had a comparable anterior support and mesh exposure rate compared with TVM alone. Trial Registration: IRB-B09904021

BACKGROUND Hysteroscopy is a traditional diagnostic method, whereas vaginoscopy is a more recent but proven approach. However, most physicians are unfamiliar with vaginoscopy. We aimed to compare the feasibility and tolerability between the two techniques to increase clinical awareness. METHODS We retrospectively reviewed the data of 100 patients who underwent office hysteroscopy with either the standard approach or the vaginoscopic approach between May and July 2019. While the standard hysteroscopy group underwent speculum insertion and the cervix was grasped with forceps, the vaginoscopy group did not. The primary outcome was a successfully completed examination. Related outcomes were the pain score, complications, and absence of signs of infection at 1 week after completing the examination. RESULTS The success rates of vaginoscopy and standard hysteroscopy were comparable (95.5% vs 96.3%). The median time to complete a vaginoscopy (135 seconds) was significantly shorter than to complete a standard hysteroscopy (190 seconds, p = 0.02). The median pain score was 3 for vaginoscopy, which was significantly lower than that for standard hysteroscopy (5; p = 0.01). There were no differences in the surgical complication rate between vaginoscopy (n = 4) and standard hysteroscopy (n = 3) (relative risk = 0.81, 95% confidence interval = 0.11-6.00). CONCLUSION Vaginoscopy required a shorter time for the completion of the examination and involved lesser pain than the standard hysteroscopy. The success rates were comparable between the two techniques. Therefore, vaginoscopy is a good option for office hysteroscopic examinations.

Epithelial ovarian cancer (EOC) is a heterogeneous disease with a variety of distinct clinical and molecular characteristics. The currently available and common research models for EOC include tumor cell lines and patient-derived xenografts. However, these models have certain shortcomings: establishing a cell line is time-consuming, loss of genetic traits after long-term culture is a possibility, and investment is required in terms of animal care facilities. Therefore, better research models are required. Organoid technology was originally developed from colorectal cancer. Tumor organoid is a three-dimensional culture system and can help accurately recapture the tumor phenotype from the original tumor. Tumor organoid systems can overcome the above-mentioned shortcomings of the currently available research models. The organoid model can be used for culturing ovarian cancer subtypes, screening drugs, assessing genomes, and establishing biobanks. However, the currently available organoid models can only culture one type of cells, epithelial cells. Therefore, an organoid-on-a-chip device can be developed in the future to provide a microenvironment for cell-cell, cell-matrix, and cell-media interactions. Thus, organoid models can be used in ovarian cancer research and can generate a simulated

The association between bladder antimuscarinic use and dementia development is unclear. We used data from the Taiwan National Health Insurance Research Database to determine the association between the exposure dose and duration of bladder antimuscarinics and the subsequent dementia risk. We enrolled participants aged 55 years or more and defined a dementia cohort (International Classification of Diseases, Ninth Revision, Clinical Modification codes 290, 294.1, and 331.0). We used a propensity score matching method, and randomly enrolled two controls without dementia. We evaluated dementia risk with respect to the exposure dose and duration of treatment with seven bladder antimuscarinics (oxybutynin, propiverine, tolterodine, solifenacin, trospium, darifenacin, and fesoterodine) used for at least 1 year before the index date, after adjusting for age, sex, comorbidities, and medications. The dementia risk was 2.46-fold (95% confidence interval: 2.22–2.73) higher in Taiwanese patients who used bladder antimuscarinics for ≥ 1 year than in those who were not exposed to this treatment. The risk proportionally increased with increasing doses of antimuscarinics for less than 4 years. Taiwanese patients aged 55 years or more on bladder antimuscarinics exhibited a higher risk of dementia. Additional studies in other countries are required to determine whether this result is valid worldwide.

Mesenchymal stem cell (MSC) therapy has been investigated intensively for many years. However, there is a potential risk related to MSC applications in various cell niches. Methods: The safety of intravitreal MSC application and the efficacy of MSC-derived conditioned medium (MDCM) were evaluated in the normal eye and the diseased eye, respectively. For safety evaluation, the fundus morphology, visual function, retinal function, and histological changes of the retina were examined. For efficacy evaluation, the MDCM was intravitreally administrated in a rodent model of anterior ischemic optic neuropathy (rAION). The visual function, retinal ganglion cell (RGC) density, and neuroinflammation were evaluated at day 28 post-optic nerve (ON) infarct. Results: The fundus imaging showed that MSC transplantation induced retinal distortion and venous congestion. The visual function, retinal function, and RGC density were significantly decreased in MSC-treated eyes. MSC transplantation induced astrogliosis, microgliosis, and macrophage infiltration in the retina due to an increase in the HLA-DR-positive MSC proportion in vitreous. Treatment with the MDCM preserved the visual function and RGC density in rAION via inhibition of macrophage infiltration and RGC apoptosis. Conclusions: The vitreous induced the HLA-DR expression in the MSCs to cause retinal inflammation and retina injury. However, the MDCM provided the neuroprotective effects in rAION.

This retrospective study aimed to compare the safety and efficacy of Prostin E2 and Propess for the induction of labor (IOL) in nulliparous women between January 2018 and October 2021. The inclusion criteria were nulliparous, singleton, >37 weeks’ gestation, cephalic presentation with an unfavorable cervix (Bishop score ≤ 6), no signs of labor, and use of one form of dinoprostone (Prostin E2 or Propess) for IOL. The cesarean section (C/S) rate and induction-to-birth interval were the main outcome measures. In total, 120 women were recruited. Sixty (50%) patients received Propess and 60 (50%) received repeated doses of Prostin E2. The Prostin E2 and Propess groups had similar patient characteristics, but the Bishop score was significantly higher in the Propess group than in the Prostin E2 group; therefore, multivariate analysis was conducted, and the Bishop score was not associated with the induction-to-birth interval. The C/S rate was not significantly different between the two groups, but the Propess group achieved a shorter induction-to-birth interval, a higher rate of vaginal delivery in 24 h, and a lower number of vaginal examinations than the Prostin E2 group. Propess was effective and safe in IOL and could be an option for cervical ripening in nulliparous pregnancy.

Simple Summary Ovulation is regarded as the culprit of ovarian high-grade serous carcinoma (HGSC). Previously, we discovered IGF2 in the ovulatory follicular fluid (FF), which bathe fallopian tube epithelium (FTE) during ovulation, promotes malignant transformation through the IGF-1R/AKT pathway. Transformed FTE cells then exfoliate and metastasize to the ovary and peritoneum to grow overt HGSC. In this study, we utilized immortalized FTE cells and HGSC cells carrying accumulating severity of driver mutations to explore FF’s role in the development of HGSC. We found FF promotes (by order of magnitude) migration, anchorage-independent growth (AIG), invasion, peritoneum attachment, anoikis resistance, and proliferation of the full panel of tested cells. The AIG activity largely depends on IGF-1R/AKT signaling, and both AKT- and non-AKT-mediated signals are responsible for other phenotypes. The results demonstrated an extensive transformation activity of FF in the full journey of HGSC development from FTE. Abstract Background: High-grade serous carcinoma (HGSC) is mainly derived from the stepwise accumulation of driver mutations in the fallopian tube epithelium (FTE), and it subsequently metastasizes to the ovary and peritoneum that develops into a clinically evident ovarian carcinoma. The developmental process involves cell proliferation/clonal expansion, cell migration, anoikis resistance, anchorage-independent growth (AIG), peritoneum attachment, and cell invasion. Previously, we discovered FTE could be transformed by follicular fluid (FF) released from ovulation, the most crucial risk factor of ovarian cancer, and IGF axis proteins in FF confers stemness activation and clonal expansion via IGF-1R/AKT pathway. However, whether other phenotypes in advanced cancer development are involved is unknown. Methods: A panel of FTE and ovarian HGSC cell lines with different severity of transformation were treated with FF with or without IGF-1R and AKT inhibitors and analyzed for the transformation phenotypes in vitro, ex vivo, and in vivo. Results: FF largely promotes (by order of magnitude) cell migration, AIG, cell invasion, peritoneum attachment, anoikis resistance, and cell proliferation. Most of these activities worked in the full panel of cell lines. The AIG activity largely depends on IGF-1R/AKT phosphorylation, and the proliferation activity depends on an AKT phosphorylation not mediated by IGF-1R. In contrast, both AKT- and non-AKT-mediated signals are responsible for the other transformation activities. Conclusions: Our data demonstrate an extensive transformation activity of FF in the full journey of carcinogenesis, and endorsed ovulation-inhibition for the prevention and AKT-inhibition for the treatment of ovarian HGSC.

The effect of hysterectomy on vesicourethral functions remains controversial. The objective of this study was to examine the association between hysterectomy and de novo lower urinary tract symptoms (LUTSs). We identified 8514 patients who had undergone hysterectomy between January 1, 2000, and December 31, 2012, from Taiwan’s National Health Insurance (NHI) Research Database. A control cohort, comprising 34,056 age-matched patients who had not undergone hysterectomy, was created for comparison. All hysterectomy and control patients were followed up until diagnosis as having LUTSs (dysuria, urinary retention, incontinence, and increased urinary frequency and urgency), withdrawal from the NHI system, death, or December 31, 2013. Patients were excluded if LUTSs were diagnosed before or at the time of hysterectomy. The adjusted hazard ratio (aHR) of subsequent de novo LUTSs was higher in the hysterectomy patients [1.57, 95% confidence interval (CI) 1.46–1.70] than in the controls during the follow-up period. Compared with the controls, the highest risk of de novo LUTSs was noted in patients who had undergone vaginal hysterectomy (VH; aHR 1.89, 95% CI 1.57–2.28) followed by those who had undergone laparoscopy-assisted VH (LAVH; aHR 1.74, 95% CI 1.56–1.94). We found that undergoing hysterectomy was associated with increased risks of developing lower urinary tract symptoms in women. This association was more pronounced for women undergoing the vaginal or laparoscopically assisted hysterectomy. Further large-scale prospective studies or clinical trials are needed to explore whether causality exists.

// Dah-Ching Ding 1, 2 , I-Ju Tsai 3, 4 , Jen-Hung Wang 5 , Shinn-Zong Lin 6 and Fung-Chang Sung 3, 7 1 Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan 2 Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan 3 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan 4 College of Medicine, China Medical University, Taichung, Taiwan 5 Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan 6 Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan 7 Department of Health Services Administration, China Medical University, Taichung, Taiwan Correspondence to: Dah-Ching Ding, email: dah1003@yahoo.com.tw Fung-Chang Sung, email: fcsung1008@yahoo.com Keywords: cardiovascular disease; coronary artery disease; diabetes mellitus; hypertension; polycystic ovary syndrome Received: August 02, 2017 Accepted: November 16, 2017 Published: January 04, 2018 ABSTRACT Women with polycystic ovary syndrome are characterized by obesity, menstruation irregularity, hirsutism and infertility, and prevalent with cardiometabolic comorbidities, but population-based studies on the risk of developing coronary artery disease are limited. From claims data of the Taiwan National Health Insurance, we identified 8048 women with polycystic ovary syndrome aged 15-49 years newly diagnosed in 1998-2013, and 32192 women without the syndrome and CAD as controls, frequency matched by age and diagnosis date. By the end of 2013, after a mean follow-up period of 5.9 years, the overall incidence of coronary artery disease was 63% higher in women with polycystic ovary syndrome than in controls (2.25 vs. 1.38 per 1000 person-years). The adjusted hazard ratio [aHR] of coronary artery disease was 1.44 (95% confidence interval (CI) = 1.14–1.81) for women with polycystic ovary syndrome, compared with controls. Hazards of coronary artery disease were significant during follow-up periods of 3-4 years (aHR = 1.52, 95% CI = 1.00–2.30) and of 5–9 years (aHR = 1.58, 95% CI = 1.07–2.32). The incidence of coronary artery disease increased further in those with cardiometabolic comorbidities. Among women with polycystic ovary syndrome, those with comorbid diabetes had an incidence of 35.2 per 1000 person-years, 20-fold greater than those without cardiometabolic comorbidities. In conclusion, women with polycystic ovary syndrome are at an elevated risk of coronary artery disease. Preventive interventions should be provided to them, particularly for those with the comorbidity of metabolism symptom.

Primitive neuroectodermal tumors (PNETs) are rare malignant tumors and extremely rare in uterine corpus. We report a case of primary uterine PNET in Taiwan. A 68-year-old woman presented with vaginal bleeding and abdominal fullness for 2 weeks. Computed tomography revealed one 8.0 cm uterine corpus tumor with carcinomatosis peritonei and ascites. The cancer antigen 125 level was high (280.7 IU/ml). Pathology of endometrial biopsy diagnosed PNET according to the characteristic of small blue round cells with Homer-Wright rosettes and Friend leukemia integration 1 transcription factor (FLI-1) positive. She received dose-dense chemotherapy with paclitaxel and carboplatin, but the response was poor and the PENT metastasized to liver. PNETs belong to small blue round cell tumor group that is difficult to be diagnosed on histopathology. The immunohistochemistry for CD99 and FLI-1 provides high sensitivity and specificity for diagnosis, respectively. No optimal treatment is established due to rarity. The prognosis is poor, usually