Preliminary study on mesenchymal stem cells in repairing nerve injury in pelvic floor denervation

Introduction: Nerve injury is considered one of the causes of pelvic floor dysfunction. Mesenchymal stem cells (MSCs) transplantation provides new possibilities for refractory degenerative diseases. This study aimed to explore the possibility and strategy of mesenchymal stem cells in treating pelvic floor dysfunction nerve injury.Methods: MSCs were isolated from human adipose tissue and cultured. A MSCs suspension (40 µL at 5 × 107/mL) was loaded on a gelatin scaffold. A rat model of anterior vaginal wall nerve injury was established by bilateral pudendal nerve denervation. The nerve tissue repair effect of mesenchymal stem cells transplanted into the anterior vaginal wall of a rat model was explored and compared in the following three groups: blank gelatin scaffold group (GS group), mesenchymal stem cell injection group (MSC group), and mesenchymal stem cells loaded on the gelatin scaffold group (MSC-GS group). Nerve fiber counting under a microscope and mRNA expression of neural markers were tested. Moreover, mesenchymal stem cells were induced into neural stem cells in vitro, and their therapeutic effect was explored.Results: Rat models of anterior vaginal wall nerve injury induced by bilateral pudendal nerve denervation showed a decreased number of nerve fibers in the anterior vaginal wall. qRT-PCR revealed that the content of neurons and nerve fibers in the rat model began to decrease 1 week after the operation and this could continue for 3 months. In vivo experiments showed that MSC transplantation improved the nerve content, and MSCs loaded on the gelatin scaffold had an even better effect. mRNA expression analysis demonstrated that MSCs loaded on gelatin scaffolds induced a higher and earlier gene expression of neuron-related markers. Induced neural stem cell transplantation was superior in improving the nerve content and upregulating the mRNA expression of neuron-related markers in the early stage.Conclusion: MSCs transplantation showed a promising repair capacity for nerve damage in the pelvic floor. The supporting role of gelatin scaffolds might promote and strengthen the nerve repair ability at an early stage. Preinduction schemes could provide an improved regenerative medicine strategy for innervation recovery and functional restoration in pelvic floor disorders in the future

Multicentre, prospective, randomised controlled trial to evaluate hexaminolevulinate photodynamic therapy (Cevira) as a novel treatment in patients with high-grade squamous intraepithelial lesion: APRICITY phase 3 study protocol

INTRODUCTION: High-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high-grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality. APRICITY is a multicentre, prospective, double-blind, randomised controlled phase 3 study further evaluating the efficacy and safety of Cevira, an integrated drug-delivery and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive outpatient therapy for women with HSIL. METHODS AND ANALYSIS: Patients with biopsy-confirmed HSIL histology are invited to participate in the study planned to be conducted at 47 sites in China and 25 sites in Ukraine, Russia and the European Union. The aim is to include at least 384 patients, which will be randomised to either Cevira or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low-grade squamous intraepithelial lesion. Primary endpoint is the proportion of the responders 6 months after first treatment. Secondary efficacy and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints of the Cevira device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira group will be enrolled in an open, long-term extension study for 6 months to collect additional efficacy and safety data (study extension endpoints). ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04484415; clinicaltrials.gov

Protective effect of gonadotropin-releasing hormone analog on the ovarian reserve in rats receiving cyclophosphamide treatment

OBJECTIVE: The aim of the study reported here was to investigate the protective effect of gonadotropin-releasing hormone analog (GnRHa) against cyclophosphamide (CTX)-induced gonadotoxicity. METHODS: Eighty Fischer 344 rats were divided randomly into four groups (20 per group). One group received normal saline, one GnRHa, one CTX, and one GnRHa+CTX. Several parameters were used to observe the ovarian reserve, including ovary weight, follicle number and diameter, concentrations of estradiol (E(2)) and follicle-stimulating hormone (FSH), and expressions of sex hormone receptors. RESULTS: When treatment was finished, the number of small follicles in the GnRHa+CTX group was significantly higher than in the CTX-alone group. Thirty days after treatment, the ovary weight, percentage of small follicles, mean follicular diameter, and serum concentrations of E(2) and FSH in the GnRHa+CTX group all recovered, approaching normal levels. Sex hormone receptors did not show significant differences between the four groups. CONCLUSION: Combination treatment with GnRHa could prevent CTX-induced damage to ovarian reserve

Management and prognosis of patients with ovarian sex cord tumor with annular tubules: a retrospective study

BACKGROUND: Owing to the rarity of sex cord tumor with annular tubules (SCTAT), it is difficult to recognize SCTAT clinically and there is no standard treatment. The aim of our study was to investigate the treatment outcomes and prognosis of patients with ovarian SCTAT. METHODS: A cohort of 13 patients with SCTAT diagnosed and treated in Peking Union Medical College Hospital was studied. Data on clinicopathological characteristics, treatment, and prognosis were retrospectively reviewed and analyzed. RESULTS: SCTAT accounted for 1.4% of ovarian sex cord stromal tumors, with an average onset age of 22.6 years. All patients presented with menstrual disturbances or isosexual precocity at disease onset. Initial surgery was unilateral salpingo-oophorectomy in 11 cases. Recurrence rate was 46.2%, and 38.5% of patients experienced multiple recurrences. The disease free interval gradually shortened with increasing numbers of recurrences. Recurrent tumors were mostly ipsilateral to the primary tumor and located in retroperitoneum. Surgery remained the main treatment for recurrent cases. Serum estradiol and progesterone levels usually elevated at disease onset, decreased dramatically after operation, and they elevated again with the development of recurrence. The median progression-free survival (PFS) was 97.8 months, and the 1-year and 5-year PFS were 92% and 67%, respectively. Five-year overall survival (OS) was 100%. CONCLUSIONS: Unilateral salpingo-oophorectomy is a feasible treatment for primary SCTAT cases with intact capsules and without PJS. Complete tumor resection is suggested for recurrent cases and long-term follow-up is strongly recommended. Despite the high risk of recurrence, SCTAT prognosis is relatively favorable

Comparison of the oncological outcomes between robot-assisted and abdominal radical hysterectomy for cervical cancer based on the new FIGO 2018 staging system: a multicentre retrospective study

Objective: To compare the 3-year oncological outcomes of robot-assisted radical hysterectomy (RRH) and abdominal radical hysterectomy (ARH) for cervical cancer. Methods: Based on the clinical diagnosis and treatment for cervical cancer in the China database, patients with FIGO 2018 stage IA with lymphovascular space invasion (LVSI)-IB2 cervical cancer disease who underwent RRH and ARH from 2004 to 2018 were included. Kaplan–Meier survival analysis was used to compare the 3-year overall survival (OS) and disease-free survival (DFS) rate between patients receiving RRH and those receiving ARH. The Cox proportional hazards model and propensity score matching were used to estimate the surgical approach-specific survival. Results: A total of 1,137 patients with cervical cancer were enrolled in this study, including the RRH group (n = 468) and the ARH group (n = 669). The median follow-up time was 45 months (RRH group vs. ARH group: 24 vs. 60 months). Among the overall study population, there was no significant difference in 3-year OS and DFS between the RRH group and the ARH group (OS: 95.8% vs. 97.6% p = 0.244). The Cox proportional hazards analysis showed that RRH was not an independent risk factor for 3-year OS (HR: 1.394, 95% CI: 0.552–3.523, p = 0.482). However, RRH was an independent risk factor for 3-year DFS (HR: 1.985, 95% CI: 1.078–3.655 p = 0.028). After 1:1 propensity score matching, there was no significant difference in 3-year OS between the RRH group and the ARH group (96.6% vs. 98.0%, p = 0.470); however, the 3-year DFS of the RRH group was lower than that of the ARH group (91.0% vs. 96.1%, p = 0.025). The Cox proportional hazards analysis revealed that RRH was not an independent risk factor for 3-year OS (HR: 1.622, 95% CI: 0.449–5.860 p = 0.461), but RRH was an independent risk factor for 3-year DFS (HR: 2.498, 95% CI: 1.123–5.557 p = 0.025). Conclusion: Among patients with stage I A1 (LVSI +)-I B2 cervical cancer based on the FIGO 2018 staging system, RRH has a lower 3-year DFS than ARH, suggesting that RRH may not be suitable for early cervical cancer patients

The prognostic and clinical value of neutrophil-to-lymphocyte ratio (NLR) in ovarian cancer: A systematic review and meta-analysis

Background: Ovarian cancer (OC) is a major gynecological malignancy with varying prognosis. The Neutrophil-toLymphocyte Ratio (NLR) has been proposed as a potential prognostic biomarker. This study aimed to evaluate the prognostic and clinical value of NLR in OC. Methods: A systematic review and meta-analysis were performed following PRISMA guidelines, including studies that evaluated the association between NLR and survival outcomes in OC patients. Search was performed in PubMed, Embase, Web of Science, and Cochrane Library databases. Quality assessment was done using Newcastle-Ottawa Scale (NOS). Heterogeneity was assessed, and pooled hazard ratios (HRs) were calculated using fixed or random-effects models as appropriate. Results: Twenty studies involving various ethnicities, ages, and sample sizes were included. A high NLR was found to be inversely correlated with overall survival (OS) (HR= 1.21, 95% CI 1.09-1.34, P<0.001) and progression-free survival (PFS) (HR=1.20, 95% CI 1.03-1.38, P<0.001). Stratified analyses showed a stronger association in Asian patients, studies with smaller sample sizes, younger patients, and higher NLR cutoff values. Conclusion: The meta-analysis suggests a significant inverse association between NLR and survival outcomes in OC patients, emphasizing NLR's potential as a simple, cost-effective prognostic biomarker. However, substantial heterogeneity and influence of confounding factors underscore the need for further investigation