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Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disorder affecting the vulvar region. VLS predominantly affects women, and most cases occur after menopause. Common symptoms include itching, skin-whitening, pain, discomfort, fissures, and scarring. Treatment options include topical steroids, emollients, lifestyle modifications, regular follow-up, and surgical interventions. Carbon dioxide (CO2) laser treatment is a therapeutic option for managing lichen sclerosus. We report a case of VLS successfully treated with a fractional microablative CO2 laser. A 72-year-old female presented with a dry vagina and vulvar itching for 6 months. She visited a local medical clinic, and oral anti-itching medication and topical anti-itching ointment were administered. However, the condition did not improve, and she felt itching. She visited our outpatient department, and a pelvic examination showed bilateral labia minor, revealing a white skin color change and a hardening sensation. The patient was diagnosed with VLS. Microablative fractional CO2 laser therapy was subsequently administered. The treatment course comprised three laser therapy sessions (treatment day, 1 month, and 2 months after the first therapy). The vulvovaginal symptoms questionnaire-21 scores were 14, 6, and 2 for the first, second, and third courses of treatment, respectively. Vulvar itching improved significantly after laser treatment – no more steroid treatment needed. After 10 months of follow-up, the condition of the vulva was maintained well. Although the treatment protocol requires further exploration, CO2 laser treatment could be considered for VLS if topical steroids are ineffective.

OBJECTIVES: This study compared the surgical outcomes of anterior vaginal wall repair (A-repair) and paravaginal repair (PVR) for laparoscopic pelvic organ prolapse (POP) surgeries. MATERIALS AND METHODS: This retrospective case–control study recruited patients who underwent laparoscopic POP surgeries in our hospital from May 1, 2013, to May 31, 2022, using the health insurance surgical code payment system (laparoscopic colpopexy/hysteropexy/cervicopexy: 80025B) in Taiwan. The patients were divided into A-repair (group 1) and PVR (group 2). Patients aged

Objective: Endometrial cancer (EC) is the most common gynecological malignancy in high-income countries. In Taiwan, the incidence of EC increased from 1.69 in 1980 to 11.36 per 100,000 women/year in 2010. Therefore, we aimed to study the prognostic factors and survival of patients with EC in southern Taiwan. Materials and methods: This study included patients with EC who underwent hysterectomy-based surgery at our hospital between 2010 and 2020. The primary outcome was 5-year progression-free survival (PFS) and overall survival (OS) of patients diagnosed with EC. The secondary outcome was the prognostic factors associated with 5-year PFS and OS in patients with EC. We used the chi-square test to assess categorical variables and the independent t-test to assess continuous variables. The Kaplan–Meier method was used to estimate survival outcomes. Cox regression analysis was conducted to examine the factors associated with PFS and OS. Results: A total of 133 patients were enrolled in this study. The mean age of the patients was 56.5 ± 10.71 years. The mean body mass index was 26.4 ± 5.21 kg/m2. The 5-year PFS and OS were 90.3% and 94.53%, respectively. In terms of PFS, endometrioid histology was linked to more favorable outcomes (hazard ratio [HR] = 0.02, 95% confidence interval [CI]:0.001–0.59), while lymph-vascular space invasion (LVSI) was associated with adverse results (HR = 9.11, 95% CI: 1.07–77.44). Initial analyses revealed no significant correlations between OS and various factors, including age, BMI, parity, DM, hypertension, age at last birth, and tumor grade. However, univariate analysis found grade 3 tumor differentiation, LVSI, and lymph node invasion associated with poorer OS. Laparoscopy was associated with better OS. Nevertheless, subsequent multivariate analysis did not reveal any factor significantly associated with OS. Most patients with EC (76.69%) underwent laparoscopic surgery. Conclusion: In conclusion, endometrioid histology was linked to more favorable PFS, while LVSI was related to adverse PFS. Our study did not identify any factors associated with OS. Two-thirds of the patients underwent minimally invasive surgery.

Abstract Secretory cells in the fallopian tube fimbria epithelium (FTE) are regarded as the main cells of origin of ovarian high-grade serous carcinoma (HGSC). Ovulation is the main cause of FTE oncogenesis, which proceeds through a sequence of TP53 mutations, chromosomal instability due to Rb/cyclin E aberration, in situ carcinoma (STIC), and metastasis to the ovary and peritoneum (metastatic HGSC). Previously, we have identified multiple oncogenic activities of the ovulatory follicular fluid (FF), which exerts the full spectrum of transforming activity on FTE cells at different stages of transformation. After ovulation, the FF is transfused into the peritoneal fluid (PF), in which the FTE constantly bathes. We wondered whether PF exerts the same spectrum of oncogenic activities as done by FF and whether these activities are derived from FF. By using a panel of FTE cell lines with p53 mutation (FT282-V), p53/CCNE1 aberrations (FT282-CCNE1), and p53/Rb aberrations plus spontaneous transformation, and peritoneal metastasis (FEXT2), we analyzed the changes of different transformation phenotypes after treating with FF and PF collected before or after ovulation. Similar to effects exhibited by FF, we found that, to a lesser extent, PF promoted anchorage-independent growth (AIG), migration, anoikis resistance, and peritoneal attachment in transforming FTE cells. The more transformed cells were typically more affected. Among the transforming activities exhibited by PF treatment, AIG, Matrigel invasion, and peritoneal attachment growth were higher with luteal-phase PF treatment than with the proliferative-phase PF treatment, suggesting an ovulation source. In contrast, changes in anoikis resistance and migration activities were similar in response to treatment with PF collected before and after ovulation, suggesting an ovulation-independent source. The overall transforming activity of luteal-phase PF was verified in an i.p. co-injection xenograft mouse model. Co-injection of Luc-FEXT2 cells with either FF or luteal-phase PF supported early peritoneal implantation, whereas co-injection with follicular-phase PF did not. This study, for the first time, demonstrates that PF from ovulating women can promote different oncogenic phenotypes in FTE cells at different stages of malignant transformation. Most of these activities, other than anoikis resistance and cell migration, are sourced from ovulation.

Background: Preserving the integrity of the endometrial cavity is crucial, particularly for preserving fertility during laparoscopic myomectomy (LM). This study aimed to compare the uterine breaching rate and clinical outcomes of LM performed with and without a uterine manipulator. Methods: Data from women who underwent LM at our hospital between January 2020 and June 2023 were retrospectively analyzed. The primary outcomes included endometrial cavity breaching rate, conversion rate, abdominal port count, operative time, hospitalization duration, and blood loss. The secondary outcomes included adverse events such as postoperative anemia and emphysema. Results: We analyzed the data from 50 participants, comparing those with (n=30) and without (n=20) manipulators. No significant differences were observed in age, body mass index, surgical time, hospitalization, blood loss, or hemoglobin drop. However, the incidence of endometrial cavity breach was higher in the manipulator group (p=0.007). The manipulator group required fewer abdominal ports (p

This study aimed to explore the role of ovarian cancer patient-derived organoids (PDOs) in their replicating genetic characteristics and testing drug responsiveness. Ovarian cancer PDOs were cultured in Matrigel with a specialized medium. The successful rate and proliferation rate were calculated. Morphology, histology, and immunohistochemistry (IHC) (PAX8, P53, and WT1) were used to identify the tumor characteristics. Gene sequencing, variant allele frequency (VAF), and copy number variation were used to explore the mutation profile. The sensitivity to chemodrugs (carboplatin, paclitaxel, gemcitabine, doxorubicin, and olaparib) was conducted. Successful generation of organoids occurred in 54% (7/13) of attempts, encompassing 4 high-grade serous carcinomas (HGSC), 1 mucinous carcinoma (MC), 1 clear cell carcinoma (CCC), and 1 carcinosarcoma. The experiments used six organoids (3 HGSC, 1 CCC, 1 MC, and 1 carcinosarcoma). The derived organoids exhibited spherical-like morphology, and the diameter ranged from 100 to 500 μm. The histology and IHC exhibited the same between organoids and primary tumors. After cryopreservation, the organoid’s growth rate was slower than the primary culture (14 days vs 10 days, P < 0.01). Targeted sequencing revealed shared DNA variants, including mutations in key genes, such as BRCA1 , PIK3CA, ARID1A , and TP53 . VAF was similar between primary tumors and organoids. The organoids maintained inherited most copy number alterations. Drug sensitivity testing revealed varying responses, with carcinosarcoma organoids showing higher sensitivity to paclitaxel and gemcitabine than HGSC organoids. Our preliminary results showed that ovarian cancer PDOs could be successfully derived and histology, mutations, and diverse copy numbers of genotypes could be faithfully captured. Drug testing could reveal the individual PDO’s responsiveness to drugs. PDOs might be as valuable resources for investigating genomic biomarkers for personalized treatment.

Endometrial atypical hyperplasia (EAH) is a premalignant condition with a substantial risk of progression to endometrial cancer (EC), with the endometrioid subtype being the most common. EAH is characterized by abnormal endometrial gland proliferation and cellular atypia, often resulting from prolonged unopposed estrogen exposure. This review aims to explore the clinical significance of EAH, its risk of progression to EC, and the current approaches to management. The risk of EAH progressing to EC ranges from 20 to 50%, influenced by factors such as histopathology and genetic mutations including PTEN and KRAS. Key risk factors include obesity, polycystic ovary syndrome, and postmenopausal status. Abnormal uterine bleeding is a hallmark symptom of EAH and early-stage EC, necessitating diagnostic evaluation through endometrial biopsy and transvaginal ultrasonography. Therapeutic management strategies depend on patient risk and fertility considerations. Hormonal therapy, particularly progestins, is the mainstay for fertility preservation, while hysterectomy is preferred for higher-risk patients. Regular monitoring with biopsies is essential for those undergoing conservative treatment. Recent advancements in the management of EAH and EC have shifted towards incorporation of molecular diagnostics and targeted therapies, enabling better risk stratification and individualized care. Biomarkers and minimally invasive surgical techniques are emerging as promising approaches in improving outcomes for women with EAH. This review underscores the importance of early diagnosis and personalized management in preventing the progression of EAH to EC, highlighting current clinical practices and potential future developments in this field.

Pelvic organ prolapse, particularly in the anterior compartment, is a prevalent condition that significantly impacts women’s quality of life. Two common surgical approaches for managing anterior vaginal wall prolapse are anterior colporrhaphy and paravaginal repair. Anterior colporrhaphy, a traditional technique, involves the plication of weakened fascial tissues to restore support to the bladder and anterior vaginal wall. Paravaginal repair addresses lateral detachment of the anterior vaginal wall by reattaching it to its supportive structures. This review aimed to compare the indications, techniques, and outcomes between these surgical methods, discussing their efficacy, recurrence rates, and complications. Although anterior colporrhaphy is widely used, paravaginal repair may offer superior results in specific cases, particularly those involving lateral defects. The review also explored the evolution of these techniques, the role of grafts and mesh, and the potential benefits of minimally invasive approaches such as laparoscopy and robotic surgery. The goal is to provide clinicians with comprehensive insights into choosing the appropriate surgical option based on individual patient anatomy and clinical presentation, thus optimizing outcomes and minimizing recurrence.

Summary: Postoperative adhesions show a higher occurrence in females aged 16–60, especially after pelvic surgeries. This study explores the role of ovulation in adhesion formation in mice. Ovarian surgery in mice with normal- or super-ovulation led to pronounced adhesions, whereas ovulation-defective Pgr-KO mice showed minimal adhesions. Specifically, exposure to ovulatory follicular fluid (FF) markedly increased the adhesion. The hazardous exposure time window was one day before to 2.5 days after the surgery. Mechanistically, early FF exposure triggered adhesions via the blood coagulation cascade, while later exposure relied on the HGF/cMET signaling pathway. Prophylactic administration of a thrombin inhibitor pre-operatively or a cMET inhibitor postoperatively effectively mitigated FF-induced adhesions, while COX inhibitor treatment exhibited no discernible effect. These findings underscore ovulation as a pivotal factor in the development of pelvic wound adhesions and advocate for targeted preventive strategies such as c-MET inhibition, scheduling surgeries outside the ovulatory period, or employing oral contraceptive measures.

Olfactory-ensheathing cells (OECs) are known for their role in neuronal regeneration and potential to promote tissue repair. Adipose-derived stem cells (ADSCs), characterized by mesenchymal stem cell (MSC) traits, display a fibroblast-like morphology and express MSC surface markers, making them suitable for regenerative therapies for osteoarthritis (OA). In this study, OECs and ADSCs were derived from tissues and characterized for their morphology, surface marker expression, and differentiation capabilities. Collagenase-induced OA was created in 10-week-old C57BL/6 mice, followed by intra-articular injections of ADSCs (1 × 105), OECs (1 × 105), or a higher dose of OECs (5 × 105). Therapeutic efficacy was evaluated using rotarod performance tests, MRI, histology, and immunohistochemistry. Both cell types exhibited typical MSC characteristics and successfully differentiated into adipocytes, osteoblasts, and chondrocytes, confirmed by gene expression and staining. Transplantation significantly improved rotarod performance and preserved cartilage integrity, as seen in MRI and histology, with reduced cartilage destruction and increased chondrocytes. Immunohistochemistry showed elevated type II collagen and aggrecan in treated joints, indicating hyaline cartilage formation, and reduced MMP13 and IL-1β expression, suggesting decreased inflammation and catabolic activity. These findings highlight the regenerative potential of OECs and ADSCs in treating OA by preserving cartilage, promoting chondrocyte proliferation, and reducing inflammation. Further research is needed to optimize delivery methods and evaluate long-term clinical outcomes.

Objectives: Pelvic floor disorders (PFDs) such as stress urinary incontinence (SUI) and pelvic organ prolapse (POP) can be managed through conservative treatments, such as conservative management involving biofeedback (BF) and electrostimulation. This study aimed to investigate the therapeutic effects of conservative treatments on PFDs. Materials and Methods: A retrospective cohort study was conducted. Women with PFD who underwent 1–3 months of BF and electrostimulation between January 1, 2020, and January 31, 2021, were included in the study. BF treatment was administered using three sensors to monitor pelvic floor muscle activity, providing patients with immediate feedback and guidance on muscle exercises. One session lasted for 5–10 min. Electrostimulation treatment utilized a specially made pelvic belt with electrode sheets to stimulate and contract pelvic floor muscles passively. One session lasted for 15 min. Six therapies in 1 month were prescribed. Pre- and post-treatment Pelvic Floor Distress Inventory (PFDI-20) scores, including POP distress inventory 6 (POPDI-6), colorectal-anal distress inventory (CRAD-8), and urinary distress inventory 6 (UDI-6) scores, were compared. Subgroup analysis by age, menopause, body mass index (BMI), and child delivery mode was performed. Results: The study included 51 women with PFDs (SUI, POP, frequency or urgency or nocturia, and pain) treated with BF and electrostimulation, with a mean age of 49.94 ± 13.63 years. Sixteen patients (37.1%) were menopausal, with a mean menopause age of 50 ± 5.20 years. Twenty-six patients (68.4%) had a history of normal vaginal delivery. The mean PFDI-20 scores before and after treatment were 32.67 (standard deviation [SD] 10.05) and 25.99 (SD 9.61), respectively (P < 0.001). This decrease in scores reflected an improvement in subjective perceptions of symptoms and quality of life. The POPDI-6, CRAD-8, and UDI-6 scores significantly decreased after treatment. Subgroup analysis of scores change regarding age, menopause, BMI, and child delivery mode was not statistically significant. Conclusion: The study demonstrated the effectiveness of BF and electrostimulation for treating women with PFDs. The findings contributed to the understanding of treatment duration, patient characteristics, and the potential benefits of a multimodal approach. Moreover, the study’s diverse participant population and the use of validated outcome measures enhance the generalizability and scientific rigor of the findings.

The incidence of urinary incontinence (UI) is approximately 10%–40% in women, affecting one to two hundred million women worldwide. Stress UI (SUI) is characterized by involuntary urination due to increased abdominal stress and urine leakage without bladder contraction. Surgical treatments include midurethral slings, bulking agents, and Burch colposuspension to restore urethral continence. Nevertheless, an optimal treatment for all types of incontinence has not yet been established. Stem-cell therapy has emerged as a novel treatment for many diseases. Stem cells can self-renew and can differentiate into other cell types. Adult stem cells are suitable for clinical applications because they can be easily obtained noninvasively or minimal invasively. Stem-cell therapy for SUI has been studied preclinically and clinically. Muscle-derived progenitors have been used to treat SUI by promoting the regeneration of rhabdomyosphincters. The human trial used transurethral injection of autologous muscle-derived stem cells to improve sphincter contractility and function. Other sources of stem cells have also been studied in SUI treatment, such as umbilical cord blood, amniotic fluid, bone marrow, urine, and adipose tissue. The success rate of stem-cell therapy for SUI ranges from 13% to 100%. This review aimed to summarize the current status of stem-cell treatments for SUI, with respect to clinical trials, cell types, transplantation routes, and dosage volume and frequency.

Objectives: This study retrospectively evaluated the effectiveness of percutaneous pulley release by our newly designed needle knife in terms of cure, relapse, and complication rates. Materials and Methods: Two hundred and fifty-seven patients were allocated into male and female groups between October 2014 and September 2021. We included patients >15 years of age with a trigger finger (TF) (types II–VI). The primary outcome was the absence of a TF and pain-free movement. In contrast, the secondary outcome included second-time surgery and the number of complications such as infection and admission for antibiotics. Results: One hundred patients were male, and 157 patients were female. Males and females had mean ages of 62.45 ± 11.76 and 61.50 ± 8.57 years, respectively. The operative time was significantly longer in males than in females (7.88 ± 6.02 vs. 6.52 ± 3.74 min in males and females, respectively, P = 0.027). However, the percentages of diabetes mellitus and gout were the same in both groups. For the percutaneous methods with our needle knife, remission of the trigger was achieved in all cases. In addition, seven patients received revision and three patients with complications. After needle surgery, topical and joint pain scores were improved in both groups (from 5.09 ± 1.31 to 0.80 ± 1.56). Conclusion: The percutaneous methods with our needle knife displayed effectiveness. The cure rate was high, and the relapse rate was low. Further large-scale clinical trials comparing percutaneous needle to open surgery for releasing the TF will be needed to confirm our results.

Mesenchymal stem cells (MSCs) were applied to the therapy for degenerative diseases, immune, and inflammation. In tumor microenvironments (TME), different sources of MSCs showed that tumor-promoting and -inhibiting effects were mediated by different signaling pathways. Cancer-associated MSCs (CaMSCs) could be recruited from bone marrow or local tissues and mainly showed tumor-promoting and immunosuppressive effects. The transformed CaMSCs preserve the characteristics of stem cells, but the properties of regulating TME are different. Hence, we specifically focus on CaMSCs and discuss the detailed mechanisms of regulating the development of cancer cells and immune cells. CaMSCs could be a potential therapeutic target in various types of cancer. However, the detailed mechanisms of CaMSCs in the TME are relatively less known and need further study.

Exosomes are phospholipid bilayer vesicles that are released by all types of cells, containing proteins, lipids, and nucleic acids such as DNAs and RNAs. Exosomes can be transferred between cells and play a variety of physiological and pathological regulatory functions. Noncoding RNAs, including micro RNAs, long noncoding RNAs, and circular RNAs, are the most studied biomolecules from exosomes and more and more studies found that noncoding RNAs play an important role in the diagnosis, prognosis, and treatment of diseases, including various types of cancer. Gynecological malignancies such as ovarian, endometrial, and cervical cancer seriously threaten women’s life. Therefore, this article reviews the roles and applications of exosomes in gynecological malignancies, including the promotion or inhibition of tumor progression and regulation of tumor microenvironments, and as potential therapeutic targets for treating gynecological cancers.

Abstract The objective of this study was to conduct a 2-year follow-up of individuals having unsatisfactory reports of Pap smears and to analyze the contributing factors. This was a retrospective study at a medical center that performed about 5000–6000 Pap smears annually in Eastern Taiwan. Women who had unsatisfactory results due to scant cellularity between January 1, 2015–December 31, 2016, were included in this study. The control group comprised age-matched women with normal Pap smears at a 1:4 ratio, during the same period. The clinical characteristics and the 2-year outcomes were followed. Patients who were unavailable for follow-up assessments or who had insufficient clinical information were excluded. Student’s t-test and chi-square test were used for continuous and categorical variables, respectively. Statistical significance was defined as a p-value 0.05]). The percentage of menopause and vaginal discharge were significantly different between the two groups. Multivariate analysis revealed that premenopausal status, increased discharge were associated with the risk of unsatisfactory Pap tests. Of the 67 women with unsatisfactory Pap tests, all tested negative for any malignancies at a 2-year follow-up assessment. Women with increased vaginal discharge and without menopause were at an increased risk of having an unsatisfactory Pap test. Our results indicate that an unsatisfactory Pap smear due to scant cellularity might not increase the risk of intraepithelial neoplasia or cancer after 2 years. Further, large-scale studies with longer follow-up periods are required.

Objective: To present a rare case of xanthogranulomatous inflammation (XI) mimicking a uterine sarcoma and invading the ureter and colon. Case report: A 66-year-old woman presented with lower abdominal pain. Pelvic examination showed tenderness over the lower abdominal region without cervical discharge. Per-rectal examination showed a hard tumor on the posterior uterine wall, while ultrasonography showed a tumor-like mass extending from the posterior uterine wall to the rectum. Magnetic resonance imaging showed signs of endometrial cancer invading the rectum. However, the tumor markers carbohydrate antigen (CA) 125, CA199, and carcinoembryonic antigen were in the normal range. Cystoscopy, panendoscopy, and colonoscopy showed no significant findings. On performing exploratory laparotomy, we observed pus and severe adhesion on the posterior uterine wall and rectum. Hysterectomy, bilateral adnexectomy, colectomy, and partial left ureter resection were performed. The final pathology showed XI. The pus culture revealed Klebsiella pneumonia and PCR revealed nocardiosis. The patient received 2 weeks of antibiotic treatment and was discharged thereafter. Conclusion: XI in elderly women is rare, and hence, differential diagnoses should be carefully considered.

Fallopian tube epithelial cells (FTECs) play a significant role in the development of high-grade serous ovarian cancer (HGSOC), but their utilization in in vitro experiments presents challenges. To address these limitations, induced pluripotent stem cells (iPSCs) have been employed as a potential solution, driven by the hypothesis that orthologous iPSCs may offer superior differentiation capabilities compared with their non-orthologous counterparts. Our objective was to generate iPSCs from FTECs, referred to as FTEC-iPSCs, and compare their differentiation potential with iPSCs derived from skin keratinocytes (NHEK). By introducing a four-factor Sendai virus transduction system, we successfully derived iPSCs from FTECs. To assess the differentiation capacity of iPSCs, we utilized embryoid body formation, revealing positive immunohistochemical staining for markers representing the three germ layers. In vivo tumorigenesis evaluation further validated the pluripotency of iPSCs, as evidenced by the formation of tumors in immunodeficient mice, with histological analysis confirming the presence of tissues from all three germ layers. Quantitative polymerase chain reaction (qPCR) analysis illuminated a sequential shift in gene expression, encompassing pluripotent, mesodermal, and intermediate mesoderm-related genes, during the iPSC differentiation process into FTECs. Notably, the introduction of WNT3A following intermediate mesoderm differentiation steered the cells toward a FTEC phenotype, supported by the expression of FTEC-related markers and the formation of tubule-like structures. In specific culture conditions, the expression of FTEC-related genes was comparable in FTECs derived from FTEC-iPSCs compared with those derived from NHEK-iPSCs. To conclude, our study successfully generated iPSCs from FTECs, demonstrating their capacity for FTEC differentiation. Furthermore, iPSCs originating from orthologous cell sources exhibited comparable differentiation capabilities. These findings hold promise for using iPSCs in modeling and investigating diseases associated with these specific cell types.

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 in vivo system, enabling studies on the heterogeneity of ovarian cancer.

Fallopian tube epithelial cells (FTEC) are thought to be the cell of origin of high-grade serous ovarian carcinoma. FTEC organoids can be used as research models for the disease. Nevertheless, culturing organoids requires a medium supplemented with several expensive growth factors. We proposed that a combined conditioned medium based on the composition of the fallopian tubes, including epithelial, stromal, and endothelial cells could enhance FTEC organoid formation. We derived two primary culture cell lines from the fimbria portion of the fallopian tubes. The organoids were split into conventional or combined medium groups based on what medium they were grown in and compared. The number and size of the organoids were evaluated. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to evaluate gene and protein expression (PAX8, FOXJ1, beta-catenin, and stemness genes). Enzyme-linked immunosorbent assay was used to measure Wnt3a and RSPO1 in both mediums. DKK1 and LiCl were added to the mediums to evaluate their influence on beta-catenin signaling. The growth factor in the combined medium was evaluated by the growth factor array. We found that the conventional medium was better for organoids regarding proliferation (number and size). In addition, WNT3A and RSPO1 concentrations were too low in the combined medium and needed to be added making the cost equivalent to the conventional medium. However, the organoid formation rate was 100% in both groups. Furthermore, the combined medium group had higher PAX8 and stemness gene expression (OLFM4, SSEA4, LGR5, B3GALT5) when compared with the conventional medium group. Wnt signaling was evident in the organoids grown in the conventional medium but not in the combined medium. PLGF, IGFBP6, VEGF, bFGF, and SCFR were found to be enriched in the combined medium. In conclusion, the combined medium could successfully culture organoids and enhance PAX8 and stemness gene expression. However, the conventional medium was a better medium for organoid proliferation. The expense of both mediums was comparable. The benefit of using a combined medium requires further exploration.

Objective: The study aimed to assess the efficacy of abdominal compression and pulmonary recruitment maneuver (CPRM) after transvaginal natural orifice transluminal endoscopic surgery (vNOTES) to alleviate post-laparoscopic shoulder pain (PLSP). Materials and methods: In this retrospective cross-sectional study conducted in a tertiary referral medical center, women who underwent vNOTES between January 2018 and May 2019 were classified into control group and CPRM group with CO2 force expelled. Data on the demographic characteristics, indications for surgery, and surgical history were collected. Postoperative pain was assessed 24 and 48 h postoperatively using the visual analog scale (VAS, 0–10). Chest radiography was used to determine the residual air volume 24 h after surgery. Results: Of 10 patients, 6 and 4 underwent vNOTES adnexal surgeries and vNOTES hysterectomy, respectively. The median volumes of residual pneumoperitoneum were 9.02 mL and 28.11 mL in the CPRM and control groups, respectively (p = 0.001). The intensity of PLSP in the CPRM and control groups were 0 ± 0 vs. 3.4 ± 3.4 and 0.4 ± 0.8 vs. 2.2 ± 2.2 24 and 48 h after surgery, respectively (p = 0.005 for 24 h and p = 0.04 for 48 h). Conclusion: CPRM might facilitate decrease in residual gas volume and PLSP after vNOTES. CPRM might be considered using in vNOTES to decrease PLSP.

Abstract This study aimed to evaluate the risk of ischemic stroke (IS) in hormone therapy (HT) with oral conjugated equine estrogen (CEE) and estradiol (E2) in postmenopausal women in Taiwan. A retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database, a population-based healthcare claims dataset. Eligible women, aged 40–65 years, who received HT with E2 and CEE orally were enrolled. The primary outcome was IS. Propensity score matching with menopausal age and comorbidities was used. Cox proportional hazard regression models were used to calculate the incidence and hazard ratios (HRs) for IS. The mean menopausal ages of the E2 and CEE groups were 50.31 ± 4.99 and 50.45 ± 5.31 years, respectively. After adjusting for age and comorbidities, the incidence of IS was 1.17-fold higher in the women treated with CEE than in those treated with E2 (4.24 vs. 3.61/1000 person-years), with an adjusted HR (aHR) of 1.23 (95% confidence interval [CI] 1.05–1.44). Moreover, HT with CEE initiated within 5 years of menopause had a higher HR than E2 (aHR = 1.20; 95% CI 1.02–1.42). In conclusion, HT with oral CEE might be associated with a higher risk of IS than E2 in postmenopausal Taiwanese women. The use of HT with CEE should be cautioned with the risk of IS.

Abstract 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.

Objective: The workload of obstetric and gynecologic (OB-GYN) physicians has been an unprecedented increase because of the decrease in the number of such physicians. This study aimed to demonstrate that the hospitalist mode was the best mode for the work-life balance of OB-GYN physicians. Materials and Methods: This was a retrospective study in a tertiary academic hospital. Patients were admitted to the labor ward for delivery. The number of deliveries performed by each OB-GYN physician in different working modes was measured. We reviewed the medical charts of women admitted for delivery as well as the shift schedule of OB-GYN physicians from January 1, 2018, to June 30, 2018. We classified deliveries into three modes: the traditional mode (patient designation), on-call mode, and the hospitalist mode. Traditional mode was the work mode currently. On-call mode and the hospitalist mode were simulated conditions. The number of deliveries and the total OB-GYN physician worked time for their shift were recorded. The differences between the three modes and between OB-GYN physicians were assessed using analysis of variance. Results: In total, 237 deliveries were recorded over 6 months (3 deliveries were excluded from our data); these deliveries were performed by four OB-GYN physicians named A to D. Significant differences in workload were noted between OB-GYN physicians working in the traditional mode and those in the on-call mode, but no significant differences were noted among those working in the hospitalist mode. All OB-GYN physicians worked an average of seven shifts, and no significant differences among them were noted. Conclusion: The hospitalist mode might be the optimal mode for OB-GYN physicians to achieve a favorable work-life balance if their original main jobs are obstetric practice.

In both normal and tumor tissues, receptor tyrosine kinases (RTKs) may be pleiotropically expressed. The RTKs not only regulate ordinary cellular processes, including proliferation, survival, adhesion, and migration, but also have a critical role in the development of many types of cancer. The Tyro3, Axl, and MerTK (TAM) family of RTKs (Tyro3, Axl, and MerTK) plays a pleiotropic role in phagocytosis, inflammation, and normal cellular processes. In this article, we highlight the cellular activities of TAM receptors and discuss their roles in cancer and immune cells. We also discuss cancer therapies that target TAM receptors. Further research is needed to elucidate the function of TAM receptors in immune cells toward the development of new targeted immunotherapies for cancer.

Endometrial cancer is the most common gynecologic cancer with high heterogeneity. However, there are limited treatment options for advanced endometrial carcinoma. In recent years, immunotherapy has broadly been used for the treatment of various cancers. However, the efficacy of immunotherapy against endometrial cancer is limited. The tumor microenvironment, including mesenchymal stem cells (MSCs), may contribute to tumor progression through cancer cells themselves and through cells of the immune system. We successfully isolated endometrial cancer–derived MSCs (EmCaMSCs) from patients and found that the population of MSCs in tumor tissues was approximately 1%–5%. The population of MSCs correlated with the stage of the disease. EmCaMSCs expressed MSC markers and exhibited trilineage differentiation ability. The programmed death ligands PD-L1 and PD-L2 were highly expressed in EmCaMSCs; their expression could be further enhanced by tumor necrosis factor-α and interferon-γ. When cocultured with peripheral blood mononuclear cells (PBMCs), anti-CD3, and anti-CD28, EmCaMSCs inhibited the proliferation of PBMCs, which were partially rescued by treatment with anti-PD-L1 antibodies. From the profile of conditioned medium of EmCaMSCs, we discovered that interleukin (IL)-8 and insulin-like growth factor–binding protein 6 could also rescue the proliferation of PBMCs. Furthermore, EmCaMSCs cocultured with IL-2-induced PBMCs exhibited decreased expression of CD56, CD4, and CD8 and showed decreased cytotoxicity toward K562 cells and endometrial cancer cells. Overall, EmCaMSCs were isolated successfully from endometrial cancer tissues and exhibited immunosuppressive effects and may be targeted for the treatment of endometrial cancer by anti-cytokine and immune checkpoint inhibitors. The percentage of MSCs in tumor stroma might predict the prognosis of endometrial cancer.

Abstract. Ectopic pregnancy is the most common cause of maternal mortality in the first trimester of pregnancy. The aim of this study was to find risk factors and clinical characteristics associated with ruptured ectopic pregnancies at a medical center in eastern Taiwan in a 19-year period. This was a retrospective observational study that included patients diagnosed with ectopic pregnancy between August 1999 and December 2018. Data about the demographic variables, initial presentation, pre-treatment beta-human chorionic gonadotropin levels, treatment routes (laparoscopy or laparotomy), surgical methods (salpingostomy or salpingectomy), operation time, blood loss amount, the status of ectopic pregnancy (ruptured or unruptured), the requirement for transfusion, and duration of hospital stay were collected. The categorical and continuous variables were analyzed using the correlation coefficients. This study included 225 women who were diagnosed as having an ectopic pregnancy. There were 49 and 176 women with unruptured and ruptured ectopic pregnancies, respectively. The beta-human chorionic gonadotropin levels, history of previous ectopic pregnancy, pelvic inflammatory disease, tubal surgery, abdominal history, and vaginal bleeding were not significantly different between the 2 groups. The ratio of women with abdominal pain was significantly higher in the ruptured ectopic pregnancy group than in the unruptured group (89.1% vs. 63.8%, respectively, P

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: We present a rare case of well-differentiated papillary mesothelioma (WDPM) found incidentally in a 59-year-old woman with endometrial cancer. Case report: A 59-year-old nulliparous obese woman with a past history of hypertension and diabetes mellitus presented with postmenopausal bleeding for 11 months. Two months prior to this admission, an episode of massive vaginal bleeding lasting for a day was noticed by the patient. Hysteroscopy was performed after her visit to our outpatient department. Papillary tumors with active bleeding were found in the uterine cavity. Endometrial biopsy showed adenocarcinoma, endometrioid type characterized by papillary architecture lined by columnar cells with mild nuclear pleomorphism. The patient proceeded to magnetic resonance imaging (MRI), which demonstrated a 6.4 × 5.5 × 4.9 cm intrauterine mass. Her tumor marker levels were elevated (CA 125 87.8 IU/ml, CA19-9160.54 IU/ml). The patient then underwent a staging surgery and final pathology revealed stage IA endometrial cancer. During surgery, multiple nodules were found in the peritoneum, initially considered as tumor metastasis and eventually proved to be WDPM. Conclusion: In conclusion, the simultaneous occurrence of WDPM with endometrial cancer is a rare entity. Although no standardized treatment has been established, WDPMs have a relatively favorable prognosis compared to malignant mesotheliomas.

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

Abstract Background Cell lines are extremely useful for both basic and clinical research. Thus, establishing endometrial cancer cell lines with malignant histology is important. This study aimed to extensively characterize an endometrial clear cell carcinoma cell line. Methods This cell line, named 150,057, was derived from the endometrial clear cell cancer of a 63-year-old woman. The morphology, chromosomes, chemosensitivity, tumor markers, xenotransplantation characteristics, and cancer-related genes of the cell line were characterized. Results This cell line exhibited adequate growth, being passaged more than 70 times. The morphology of the cells was polygonal with a cobblestone-like appearance. Karyotyping of the cell line revealed a hypodiploid chromosomal number. 150057 cells expressed CA19–9 and CA125. The cell line was sensitive to doxorubicin, paclitaxel, carboplatin, and cisplatin. After the cells were transplanted into the subcutaneous region of non-obese diabetic-severe combined immunodeficiency mice, they generated xenograft tumors with similar histology as the original tumor. A total of 59 somatic nucleotide mutations were identified in 25 of the 53 examined tumor suppressor genes and oncogenes. Two novel mutations were found in FGFR3 and ARID1A. Conclusion We established and characterized an endometrial clear cell carcinoma cell line that may be useful in carcinogenesis and treatment research for endometrial cancer.

Abstract 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.

Objectives: The objective of this study is to compare the outcomes of laparoscopic hysteropexy (LHP) and laparoscopic supracervical hysterectomy plus cervicopexy (LSHCP) for the treatment of pelvic organ prolapse (POP). Materials and Methods: We retrospectively included patients who had undergone laparoscopic sacral hysteropexy or hysterectomy plus cervicopexy between January 2015 and May 2019 at Hualien Tzu Chi Hospital, Taiwan. Age at surgery, body mass index (BMI) at admission, the initial stage of genital prolapse, operative and postoperative data, and anatomical results were recorded. Cure for uterine prolapse was evaluated objectively through vaginal examinations using the POP quantification scale. Visual analog scale (VAS) scores were recorded at 24 h postoperatively. The Mann–Whitney U-test was used to compare continuous variables. Results: A total of 23 women were included in the study; 12 had received LHP (n = 12) and 11 had received LSHCP (n = 11). No differences existed in age, parity, BMI, blood loss, or hospital stay between groups. The difference in mean surgical times between the LHP and LSHCP groups was nonsignificant (154 and 176 min, respectively;P = 0.2). VAS scores were significantly lower in the LSHCP group than in the LHP group (0.1 vs. 1.75; P = 0.004). Furthermore, mean hospital stay was significantly longer in the LSHCP group than in the LHP group (4.0 vs. 3.1 days; P = 0.016). The procedure was successful in 100% of patients (23 of 23), with no objective evidence of uterine prolapse on examination at follow-up at 6 months. Conclusion: LHP had a significantly shorter hospital stay and a higher VAS score than LSHCP. LHP and LSHCP are both feasible and effective procedures for correcting uterine prolapse.

There is an increasing interest in generating retinal pigment epithelial (RPE) cells from stem cells for treating degenerative eye diseases. However, whether human umbilical cord mesenchymal stem cells (HUCMSCs) can differentiate into RPE-like cells in a co-culture system has not been fully understood. In this study, induction of HUCMSC differentiation into RPE-like cells was performed by co-culturing HUCMSCs and a human RPE-like cell line (ARPE19) in a transwell system and then analyzed for biomarkers using quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining technique. Moreover, the functional characterization of induced cells was carried out by examining their phagocytic and neurotrophic factor–secreting activities. Our results showed that mRNA expressions of RPE-specific markers—MITF, OTX2, RPE65, PEDF, PME17, and CRALBP—and protein markers—RPE65, CRALBP, and ZO-1—were significantly increased in HUCMSC-derived RPE-like cells. Functional characteristic studies showed that these induced cells were capable of engulfing photoreceptor outer segments and secreting brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF), which are typical functions of RPE-like cells. Overall, the study findings indicate that the morphology and proliferation of HUCMSCs can be maintained in a serum-free medium, and differentiation into RPE-like cells can be induced by simply co-culturing HUCMSCs with ARPE19 cells. Thus, the study provides fundamental information regarding the clinical-scale generation of RPE-like cells from HUCMSCs.

Leiomyoma is the most common benign neoplasm of the reproductive organs in women. Retroperitoneal hydropic leiomyoma is rare type of myoma. Herein, we present the case of a 46-year-old (gravida 0) woman with retroperitoneal hydropic leiomyoma that was preoperatively diagnosed as an ovarian cyst. Transvaginal sonography and abdominal computed tomography revealed a mass, measuring 8.1×3.8 cm, with solid and cystic components in the right pelvic cavity. The patient underwent laparoendoscopic single-site surgery for the tumor excision. During the surgery, a retroperitoneal cystic tumor was resected from the right retroperitoneal cavity. Histopathologic and microscopic examinations revealed a hydropic leiomyoma with infarction. This case is impressive because of the rare location and hydropic degeneration of the leiomyoma. Furthermore, it mimicked an ovarian cyst at its initial presentation making accurate diagnosis difficult. By warning of this case, surgeons can recognize the disease entities and provide the necessary treatment.

This retrospective cohort study aimed to evaluate the factors related to endometrial cancer (EC) prognosis and survival in eastern Taiwan. The study involved 48 patients diagnosed with EC who underwent hysterectomy-based surgery at Hualien Tzu Chi hospital between January 2011 and June 2021. The patients’ medical history and laboratory examination results were reviewed. Progression-free survival and overall survival were determined. Categorical variables were analyzed using the chi-square test, and continuous variables were analyzed using the independent t-test. The receiver operating characteristic curve was used to predict diagnostic value. Factors associated with cancer mortality were identified via Cox regression analysis (p < 0.05). Patients were divided into the death (n = 7) and survival (n = 41) groups. The median age of the patients was 56 years (range: 31–71 years). The median observation period was 33.29 months. Diabetes mellitus (DM) and monocyte/lymphocyte ratio (MLR) > 0.23886 were significantly associated with cancer mortality (p = 0.024 and p = 0.028, respectively). MLR-low and MLR-high groups exhibited 5-year overall survival rates of 96% and 60%, respectively, and 5-year progression-free survival rates of 96% and 41%, respectively. DM and MLR of >0.2386 were suggested to be associated with cancer death, poor overall survival, and progression-free survival.

Osteoarthritis (OA) is characterized by the loss of articular cartilage and is also an age-related disease. Recently, stem cell therapy for cartilage repair has emerged. The stem cells need to be cultured with a fetal bovine serum (FBS)-supplemented medium. The effect of FBS-containing exosomes on the differentiation of human umbilical cord mesenchymal stem cells (HUCMSCs) is unknown. The morphology, proliferation, surface marker expressions, and trilineage differentiation ability of two groups of HUCMSCs, cultured with conventional (FBS) and exosome-depleted FBS (Exo(-)FBS), were evaluated. In a mouse OA model after two groups of HUCMSCs transplantation, the rotarod activity, histology, and immunohistochemistry (type II collagen, aggrecan, IL-1β, and MMP13) of the cartilage were evaluated. The Exo(-)FBS-cultured HUCMSCs, like FBS-cultured HUCMSCs, displayed classic MSC characteristics, including spindle-shaped morphology, surface marker expression (positive for CD44, CD73, CD90, CD105, and HLA-ABC and negative for CD34, CD45, and HLA-DR), and trilineage differentiation (chondrogenesis, osteogenesis, and adipogenesis). The Exo(-)FBS-cultured HUCMSCs proliferated significantly slower than those of the FBS-cultured HUCMSCs (p < 0.01). The trilineage gene expression of PPAR-γ, FABP4, APAL, type II collagen, aggrecan, and SOX9 was significantly increased in the Exo(-)FBS-cultured HUCMSCs than in the FBS-cultured HUCMSCs and undifferentiated controls. The Exo(-)FBS- and FBS-cultured HUCMSCs-transplanted mice showed a better rotarod activity than in the control OA mice (n = 3 in each group). A significant histological improvement in hyaline cartilage destruction after the transplantation of both types of FBS-cultured HUCMSCs was noted when compared with the OA knees. The Exo(-)FBS-cultured HUCMSCs-transplanted knees showed a higher International Cartilage Repair Society histological score (p < 0.05), staining intensity of type II collagen (p < 0.01), and aggrecan (p < 0.01) than in the control knees. Moreover, both types of the FBS-cultured HUCMSCs-transplanted knees significantly decreased the expression of MMP13 and IL-1β compared to that in the OA knees (p < 0.01). The Exo(-)FBS-cultured HUCMSCs harbor chondrogenic potential and attenuated cartilage destruction in a mouse OA model. Our study provides a basis for future clinical trials using Exo(-)FBS-cultured stem cells to treat OA.

Background: The fallopian tube fimbria is regarded as the main tissue of origin and incessant ovulation as the main risk factor of ovarian high-grade serous carcinoma. Previously, we discovered the tumorigenesis activity of human ovulatory follicular fluid (FF) upon injection to the mammary fat pad of Trp53-null mice. We also found a mutagenesis activity of FF-ROS and a apoptosis-rescuing activity of Hb from retrograde menstruation. However, neither of them can explain the tumorigenesis activities of FF. Methods: From two cohorts of ovulatory FF retrieved from IVF patients, the main growth factor responsible for the transformation of human fimbrial epithelial cells was identified. Mechanism of activation, ways of signal transduction of the growth factor, as well as the cellular and genetic phenotypes of the malignant transformation was characterized. Findings: In this study, we showed that insulin-like growth factor (IGF)-axis proteins, including IGFBP-bound IGF2 as well as the IGFBP-lytic enzyme PAPP-A, are abundantly present in FF. Upon engaging with glycosaminoglycans on the membrane of fimbrial epithelial cells, PAPP-A cleaves IGFBPs and releases IGF2 to bind with IGF-1R. Through the IGF-1R/AKT/mTOR and IGF-1R/AKT/NANOG pathways, FF-IGF leads to stemness and survival, and in the case of TP53/Rb or TP53/CCNE1 loss, to clonal expansion and malignant transformation of fimbrial epithelial cells. By depleting each IGF axis component from FF, we proved that IGF2, IGFBP2/6, and PAPP-A are all essential and confer the majority of the transformation and regeneration activities. Interpretation: This study revealed that the FF–IGF axis functions to regenerate tissue damage after ovulation and promote the transformation of fimbrial epithelial cells that have been initiated by p53- and Rb-pathway disruptions. Fund: The study was supported by grants of the Ministry of Science and Technology, Taiwan (MOST 106-2314-B-303-001-MY2; MOST 105-2314-B-303-017-MY2; MOST 107-2314-B-303-013-MY3), and Buddhist Tzu Chi General Hospital, Taiwan (TCMMP104-04-01). Keywords: Ovarian high-grade serous carcinoma, Follicular fluid, Fallopian tube fimbriae, IGF axis, Stemness

Objectives: Osteoarthritis (OA) is a chronic disease of degenerative joints. Mesenchymal stem cells (MSCs) have been used for cartilage regeneration in OA. We investigated the therapeutic potential of human umbilical cord-derived MSCs (HUCMSCs) with hyaluronic acid (HA) hydrogel transplanted into a porcine OA preclinical model. Materials and Methods: The HUCMSCs were characterized with respect to morphology, surface markers, and differentiation capabilities. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to examine gene expressions in a HUCMSC–HA coculture. Two healthy female minipigs weighing 30–40 kg and aged approximately 4 months were used in this large animal study. A full-thickness chondral injury was created in the trochlear groove of each of the pig's rear knees. After 3 weeks, a second osteochondral defect was created. Then, 1.5 mL of a HUCMSC (5 × 106 cells) and HA composite (4%) was transplanted into the chondral-injured area in the right knee of each pig. Using the same surgical process, an osteochondral defect (untreated) was created in the left knee as a control. The pigs were sacrificed 12 weeks after transplantation. Macroscopic and microscopic histologies, qRT-PCR, and immunostaining evaluated the degree of chondral degradation. Results: The HUCMSCs exhibited typical MSC characteristics, including spindle morphology, expression of surface markers (positive for CD29, CD4, CD73, CD90, and human leukocyte antigen [HLA]-ABC; negative for CD34, CD45, and HLA-DR), and multipotent differentiation (adipogenesis, osteogenesis, and chondrogenesis). More extensive proliferation of HUCMSCs was noted with 4% and 25% of HA than without HA. Expression of COL2A1 and aggrecan in the HUCMSC-derived chondrocytes was increased when HA was included. The treated knees showed significant gross and histological improvements in hyaline cartilage regeneration when compared to the control knees. The International Cartilage Repair Society histological score was higher for the treated knees than the control knees. Conclusion: Our findings suggest that cartilage regeneration using a mixture of HUCMSCs and HA in a large animal model may be an effective treatment for OA, and this study is a stepping stone toward the future clinical trials.

Vitamin D deficiency is common globally with a higher prevalence in women, especially during pregnancy. Among the pregnant women, Vitamin D deficiency was reported up to 80% in the Asian group. Vitamin D deficiency was related to a higher risk of maternal complications including preeclampsia, impaired glucose tolerance, and cesarean section rate, and neonatal complications including low birthweight, neonatal hypocalcemia seizure, and impaired skeletal, lung and immune development. There were no data supporting Vitamin D deficiency screening routinely in pregnancy regarding cost-effectiveness or health benefits. The measurement of Vitamin D in the high-risk group of women is necessary. Subsequent supplement with Vitamin D with and without calcium supplement during pregnancy had been statistically significantly reported to decrease the risk of preeclampsia, preterm birth, and low birth body weight. However, due to a lack of studies, the strategies of dietary and nutritional supplement for fetal growth restriction prevention are not statistically effective and are not yet recommended. The present review is to provide an overview of the clinical and the experimental evidence of Vitamin D deficiency-related complication and review of available options for the prevention and management of these complications.

AimLower urinary tract symptoms (LUTS) result in morbidities; however, their association with the occurrence of hip fracture is relatively unknown in the context of Asian studies. The purpose of the study was to investigate this link with the hip fracture risk in Taiwanese men and women aged 50 years and above.Materials and methodsFrom 2000 through 2012, a population-based retrospective cohort study was conducted; claims data of 18,976 patients diagnosed with LUTS (dysuria, urinary retention, incontinence, and increased urinary frequency and urgency) were retrieved from Taiwan's National Health Insurance Research Database. The patients were compared with 1:2 age, sex, and index year-matched controls (comparison group, n = 37,952). The incidence and hazard ratios of the hip fracture risk were calculated by the Cox proportional hazard regression models.ResultsThe mean age was 66.2 ± 9.7 years, and the proportion of men was 58.1% in both study groups. Fractures occurred in 772 patients and 1,156 control subjects. The corresponding incidences were 7.0 and 5.0/1000 person-years. Compared to the control subjects, the patients with LUTS had an increased hip fracture risk [adjusted hazard ratio (aHR) = 1.29; 95% confidence interval (CI): 1.17-1.42]. LUTS was independently associated with an increased hip fracture risk in both men (aHR = 1.24; 95% CI: 1.08-1.42) and women (aHR = 1.34; 95% CI: 1.18-1.53) (p for interaction = 0.557). Similarly, the subgroup effect of age on hip fracture risks was not found (p for interaction = 0.665).ConclusionThe study found LUTS was associated with an increased risk of hip fracture. Large-scale prospective studies in diverse populations are required to investigate causalities.

ObjectivesMost research into the management of pelvic inflammatory disease (PID) is in younger women and focuses on sexually transmitted pathogens such as N. gonorrhoeae or C. trachomatis. Non-sexually transmitted bacterial pathogens and PID in older women are rarely examined. The objective of this study is to explore cervical culture pathogens in women of different age groups in a medical center in eastern Taiwan.MethodsWe enrolled patients whose medical records were diagnosed with PID (ICD-9-CM 614.0 [N70.01-03], 614.1[N70.11-13], 614.9 [N73.5, N73.9]) at our hospital from October 2014 to March 2020. Patients were divided into three groups according to age: the age ResultsA total of 96 patients were included in the study. There were 31 patients in the age ≥ 45 years group, 52 patients in the age 25-44 years group, and 13 patients in the age ConclusionsThis may be due to different pathogeneses of PID in the age ≥ 45 years patients. Our study can be used as a reference for antibiotic choice of non-sexually transmitted PID and to prevent long-term sequelae of PID.

Osteoarthritis (OA), the most common type of arthritis, causes pain in joints and disability. Due to the absence of ideal effective medication, stem cell transplantation emerges as a new hope for OA therapy. This study is aimed at evaluating the capability of human umbilical cord mesenchymal stromal cells (HUCMSCs) mixed with hyaluronan (HA) to treat osteoarthritis in a rabbit model. Differentiation capability of HUCMSCs, magnetic resonance image examination, and immunohistochemistry of the cartilage after transplantation of HUCMSCs mixed with HA in a rabbit OA model were explored. HUCMSCs exhibited typical mesenchymal stromal cell (MSC) characteristics, including spindle-shaped morphology, surface marker expressions (positive for human leukocyte antigen- (HLA-) ABC, CD44, CD73, CD90, and CD105; negative for HLA-DR, CD34, and CD45), and trilineage differentiation (chondrogenesis, adipogenesis, and osteogenesis). The gene expression of SOX9, type II collagen, and aggrecan in the HUCMSC-derived chondrocytes mixed with HA was increased after in vitro chondrogenesis compared with HUCMSCs. A gross and histological significant improvement in hyaline cartilage destruction after HUCMSCs mixed with HA was noted in the animal model compared to the OA knees. The International Cartilage Repair Society histological score and Safranin O staining were significantly higher for the treated knees than the control knees (p

AimThis study investigated the risk of osteoporosis or bone fractures (vertebrae, hip and others) in hysterectomized women in Taiwan.Materials and methodsThis is a retrospective population-based cohort study from 2000 to 2013. Women aged ≥30 years who underwent hysterectomy between 2000 and 2012 were included in this study. The comparison group was randomly selected from the database with a 1:4 matching with age and index year. Incidence rate and hazard ratios of osteoporosis and bone fracture between hysterectomized women and the comparison group were calculated. Cox proportional hazard regressions were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsWe identified 9,189 hysterectomized women and 33,942 age-matched women without a hysterectomy. All women were followed for a median time of about 7 years. The adjusted hazard ratio (aHR) of subsequent osteoporosis or bone fracture was higher in the hysterectomy women (2.26, 95% confidence interval [CI] = 2.09-2.44) than in the comparison group. In the subgroup analysis, oophorectomy and estrogen therapy increase the risk of osteoporosis or fracture in both groups. Regarding the fracture site, the aHR of vertebral fracture (4.92, 95% CI = 3.78-6.40) was higher in the hysterectomized women than in the comparison group. As follow-up time increasing, the aHR of vertebral fracture in hysterectomized women were 4.33 (95% CI = 2.99-6.28), 3.89 (95% CI = 2.60-5.82) and 5.42 (95% CI = 2.66-11.01) for ConclusionsIn conclusion, we found that hysterectomized women might be associated with increased risks of developing osteoporosis or bone fracture.

The aim of this study was to explore the therapeutic effect of iPSC-mesenchymal stem cell (MSC)-derived chondrocytes in a rabbit osteoarthritis (OA) model. The iPSCs were characterized by gene expressions, immunostaining of pluripotent markers, and in vivo teratoma formation. iPSC-differentiated MSCs were characterized by flow cytometry and trilineage differentiation. A rabbit OA model was established by the transection of the anterior cruciate ligament. The therapeutic effect of transplanted iPSC-MSC-chondrocytes on the OA was evaluated by the histology, immunostaining, and qPCR of defective cartilage. The results showed iPSC could express pluripotency markers such as OCT4, SOX2, and NANOG and form an embryoid body and a teratoma. After differentiation of iPSCs for 30 days, MSCs were established. The iPSC-MSC could express typical MSC markers such as CD29, CD44, CD90, CD105, and HLA-ABC. They could differentiate into adipocytes, osteocytes, and chondrocytes. In this model, iPSC-MSC-chondrocytes significantly improved the histology and ICRS (International Cartilage Repair Society) scores. The transplanted cartilage expressed less IL-1β, TNF-α, and MMP13 than control cartilage. In conclusion, the iPSCs we derived might represent an emerging source for differentiated MSC-chondrocyte and might rescue cartilage defects through its anti-inflammatory and anti-catabolic effects.

Objective: We describe the first case of a rare undifferentiated uterine sarcoma exhibiting both neuroectodermal differentiation and osteoclast-like giant cells, and elaborate its morphology. Case report: A 54-year-old woman presented with suprapubic pain, frequent urination, and perimenopausal abnormal vaginal bleeding. Computed tomography revealed a large heterogeneous uterine mass and multiple lung nodules. She received a staging surgery. The tumor pathology examination revealed an undifferentiated uterine sarcoma (UUS) with neuroectodermal differentiation and osteoclast-like giant cells (OGCs). The patient was managed with palliative hospice care; however, she died within 1.5 months of diagnosis. Conclusion: UUSs are rare high-grade tumors observed in elderly women. These women typically present with postmenopausal bleeding and extrauterine diseases and have a poor prognosis. Neuroectodermal differentiation in UUSs has a müllerian origin. The presence of OGCs may suggest a poor prognosis; however, further studies are necessary to determine the exact nature of such neoplasms.

Objective: The present study investigated the therapeutic potential and underlying mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) on joint cartilage destruction induced by monosodium iodoacetate (MIA) in mice. Materials and Methods: HUCMSCs were tested for mesenchymal stem cell (MSC) characteristics including surface markers by flow cytometry and mesoderm differentiation (adipogenesis, osteogenesis, and chondrogenesis). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Western blot assay were used to evaluate MIA-induced chondrocyte apoptosis. In the in vivo study, 18 mice were divided into three groups (n = 6 each); normal saline (control), MIA-treated, and MIA-treated/HUCMSC-transplantation. Rota-Rods tests were used to evaluate MIA-induced cartilage destruction behaviors in mice. Histological changes in the mice cartilage were examined by immunohistochemistry. Results: HUCMSCs had an immunophenotype similar to bone marrow-derived MSCs and were able to differentiate into adipocytes, osteocytes, and chondrocytes. Conditioned medium of the HUCMSCs exhibited an anti-apoptotic effect and inhibited expression of caspase 3 in MIA-treated chondrocytes. HUCMSC transplantation assisted in recovery from movement impairment (from 30% on day 7 to 115% on day 14) and in regeneration and repair of cartilage damaged by MIA. (International Cartilage Repair Society score: 3.8 in the MIA group vs. 10.2 in the HUCMSC-treated group); HUCMSC transplantation ameliorated cartilage apoptosis through the caspase 3 pathway in MIA-induced cartilage destruction in mice. Conclusion: Taken together, these observations suggest that HUCMSC transplantation appears to be effective in protecting cartilage from MIA damage.

Natural orifice transluminal endoscopic surgery (NOTES) had been used for many gynecologic surgeries without pelvic adhesions. We report a 30-year-old female with multiple abdominal adhesions underwent NOTES hysterectomy successfully. A 30-year-old female (para 2, gravida 3, abortus 1) presented with menorrhagia and dysmenorrhea. She had multiple abdominal surgical histories. Computed tomography scan revealed multiple adhesions between the abdominal wall and small intestine. On pelvic ultrasonography, an enlarged uterus 8.3 cm × 3.5 cm with adenomyosis was visualized. Because of the extensive intra-abdominal adhesions, we decided to use a transvaginal NOTES approach to perform hysterectomy. We performed the surgery successfully without complication. Pathological examination confirmed adenomyosis of uterus. NOTES hysterectomy may be feasibly and safely performed in gynecologic patients with extensive abdominal adhesions.

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