LncRNA TRPM2-AS promotes endometrial carcinoma progression and angiogenesis via targeting miR-497-5p/SPP1 axis.

BACKGROUND: Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear. METHODS: We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS's function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC. RESULTS: We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes. CONCLUSION: The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS's role in regulating angiogenesis and provides a novel target for EC treatment.

Biomaterial Fg/P(LLA-CL) regulates macrophage polarization and recruitment of mesenchymal stem cells after endometrial injury.

The process of endometrial repair after injury involves the synergistic action of various cells including immune cells and stem cells. In this study, after combing Fibrinogen(Fg) with poly(L-lacticacid)-co-poly(ε-caprolactone)(P(LLA-CL)) by electrospinning, we placed Fg/P(LLA-CL) into the uterine cavity of endometrium-injured rats, and bioinformatic analysis revealed that Fg/P(LLA-CL) may affect inflammatory response and stem cell biological behavior. Therefore, we verified that Fg/P(LLA-CL) could inhibit the lipopolysaccharide (LPS)-stimulated macrophages from switching to the pro-inflammatory M1 phenotype in vitro. Moreover, in the rat model of endometrial injury, Fg/P(LLA-CL) effectively promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype and enhanced the presence of mesenchymal stem cells at the injury site. Overall, Fg/P(LLA-CL) exhibits significant influence on macrophage polarization and stem cell behavior in endometrial injury, justifying further exploration for potential therapeutic applications in endometrial and other tissue injuries.

Nano-biomaterial Fibrinogen/P(LLA-CL) for prevention of intrauterine adhesion and restoration of fertility.

Endometrial damage resulting from surgical procedures is a significant cause of intrauterine adhesion, thin endometrium, and subsequent miscarriage and infertility. Unfortunately, there is currently no effective clinical solution to promote endometrial regeneration after severe injury. In this study, we combined fibrinogen (Fg) and P(LLA-CL) by electrostatic spinning to form a stable nano-biomaterial Fg/P(LLA-CL), which can promote endometrial regeneration. After inducing physical injury to rat endometrium, we found that Fg/P(LLA-CL) membranes placed in the uterine cavities increased endometrial thickness and the number of glands after injury, while reducing the area of endometrial fibrosis. In addition, Fg/P(LLA-CL) increased neovascularization and decreased COL1A1 deposition. The expression of TGF-ß1, a cytokine that promotes fibrosis, was down-regulated in the early stage of injury. Finally, fertility assays confirmed that Fg/P(LLA-CL) improved the pregnancy rate in rats with endometrial injury, and its safety was verified by blood tests and pathological examination of heart, liver, spleen, lung, and kidney. Therefore, Fg/P(LLA-CL) shows great potential as a safe and nontoxic biomaterial for endometrial regeneration, ultimately improving pregnancy outcomes in patients with intrauterine adhesion.

Impact of peritoneal vaginoplasty combined with radical hysterectomy on the quality of sexual life for patients with early-stage cervical cancer: trial protocol for a multi-center superiority randomized controlled trial.

BACKGROUND: Radical hysterectomy (RH) is commonly used to treat early-stage cervical cancer in women of childbearing age and sexual dysfunction due to postoperative vaginal shortening is a major concern. The impact of intraoperative vaginoplasty on prognosis and quality of sexual life in patients with early-stage cervical cancer remains controversial and lacks high-level evidence. However, there are few reports on vaginoplasty after RH to lengthen vagina in patients. This prospective, multi-center, randomized controlled trial aims to explore the impact of peritoneal vaginoplasty with or without ovarian transposition after laparoscopic RH on sexual dysfunction in patients with early-stage cervical cancer. METHODS: Eligible patients will be randomly assigned (1:1) to receive peritoneal vaginoplasty or not. The primary evaluation indicators are female sexual function index (FSFI) and male sexual satisfaction scale. The secondary evaluation indicators include EORTC QLQ-CX24, 2-year overall survival (OS), 5-year OS, 2-year progression-free survival (PFS), 5-year PFS and surgery-related complications. The trial will enroll 368 patients from 6 hospitals in China over a 3-year period and follow up for 5 years. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2000040610.

TEM1 up-regulates MMP-2 and promotes ECM remodeling for facilitating invasion and migration of uterine sarcoma.

OBJECTIVES: To explore the correlation between tumor endothelial marker 1 (TEM1) and matrix metalloproteinase 2 (MMP-2) in uterine sarcoma and their roles in the progression of uterine sarcoma. METHODS: Uterine leiomyosarcoma (uLMS, n = 25) and uterine leiomyoma (n = 25) specimens were collected from a total of 50 patients. Immunohistochemistry assay was conducted to determine the expression of TEM1, MMP-2 and MMP-9. TEM1 over expression (hTEM1) and low expression (shRNA-TEM1) MES-SA cell lines were established as in vitro uterine sarcoma models. MMP-2 mRNA, protein expression and enzymatic activity were verified using qPCR, Western blot and gelatin zymography respectively. MMP-2 expression was downregulated using MMP-2 siRNA in hTEM1 MES-SA cells to better study the role of MMP-2. The invasive and migratory capacities of hTEM1, shRNA-TEM1, and hTEM1 treated with MMP-2 siRNA MES-SA cells were determined using transwell assays. Extracellular matrix (ECM) remodeling mediated by TEM1 was examined using cell-ECM adhesion and fluorescent gelatin-ECM degradation assays. The immunofluorescence of F-actin was examined to analyze the formation of invadopodia. Subcutaneous and intraperitoneal xenografts were established to validate the role of TEM1 in promoting uterine sarcoma metastasis. RESULTS: TEM1 and MMP-2 were expressed in 92% (n = 23) and 88% (n = 22) of uterine leiomyosarcoma specimens, respectively. Both TEM1 and MMP-2 were highly expressed in 100% (n = 17) of high stage (III-IV) uterine leiomyosarcoma specimens. In addition, TEM1 expression was positively correlated with MMP-2 expression in uterine leiomyosarcoma. The successful establishment of in vitro uterine sarcoma models was confirmed with qPCR and Western blotting tests. TEM1 promoted the invasion and metastasis of uterine sarcoma in vivo and in vitro. MMP-2 expression and activity were up-regulated in hTEM1 cells but down-regulated in shRNA-TEM1 cells. Importantly, MMP-2 knockdown impaired the invasive and migratory capacity of hTEM1 cells. TEM1 promoted ECM remodeling by increasing cell-ECM adhesion and ECM degradation. TEM1 overexpression also induced the formation of invadopodia. CONCLUSION: TEM1 was co-expressed and positively correlated with MMP-2 in uterine leiomyosarcoma specimens. In addition, both TEM1 and MMP-2 were associated with tumor development. TEM1 promoted uterine sarcoma progression by regulating MMP-2 activity and ECM remodeling.

Bioinformatically deciphering immune cell infiltration and signature genes in pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The study is aimed at bioinformatically deciphering immune cell infiltration, signature genes, and their correlations in POP. METHODS: Three microarray datasets were included. Matrixes representing the uterosacral ligament were merged as a test matrix and the others representing vaginal tissues were merged as a validation matrix. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was performed to evaluate immune cell infiltration. Correlations among differential immune cells were revealed by Spearman's rank correlation. Differentially expressed genes (DEGs) were screened by both "Batch correction" and "RobustRankAggreg" methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes were conducted for functional analysis. Hub genes were identified through cytoHubba of Cytoscape, and further validated by a validation matrix and clinical samples as signature genes. Correlations of differential immune cells with signature genes were analyzed by Spearman's rank correlation. RESULTS: Five differential immune cells (macrophages, monocytes, regulatory T cell [Treg], type 1 T cell [Th1], and natural killer T cells [NKT]) were identified and eight pairs of immune cells had significant correlations. Screened 230 DEGs were extracellular matrix (ECM) and immune related. Eleven hub genes were initially identified and five of them (LOX, IL-6, SDC1, ICAM1, and CD38) were validated as signature genes. Significant correlations of differential immune cells with signature genes were shown in twelve pairs, especially Th1-IL6, NKT-IL6, Th1-ICAM1, macrophage-IL6, and macrophage-LOX pairs. CONCLUSIONS: Pelvic organ prolapse could be considered immune related. Significantly infiltrated immune cells may contribute to the development of POP through close involvement with ECM- and immune-related signature genes.

Six-year follow-up outcomes of the P(LLA-CL)/Fg bio-patch for anterior vaginal wall prolapse treatment.

INTRODUCTION AND HYPOTHESIS: There were few data about the long-term outcomes of bio-compatible patches for pelvic organ prolapse (POP). The efficacy of poly (L-lactide-co-caprolactone) blended with fibrinogen [P(LLA-CL)/Fg] bio-patches were investigated for anterior vaginal wall prolapse treatment in a 6-year follow-up. METHODS: The P(LLA-CL)/Fg bio-patch was fabricated through electrospinning. Nineteen patients with symptomatic anterior prolapse (Pelvic Organ Prolapse Quantification [POP-Q] stage ≥ 2) were treated with anterior pelvic reconstruction surgery using a P(LLA-CL)/Fg bio-patch and were followed up at 1, 2, 3, 6 months, and 6 years. The primary outcome was objective anatomical cure (anterior POP-Q stage ≤ 1). Secondary outcomes included complications, MRI evaluation, and scores of the Pelvic Floor Impact Questionnaire-7 (PFIQ-7) and the Pelvic Floor Distress Inventory-20 (PFDI-20). RESULTS: The micro-morphology of the bio-patch resembled the extracellular matrix, which was suitable for the growth of fibroblasts. Sixteen (84.2%) patients were finally assessed, with a mean follow-up of 6.08 ± 0.18 years. The cure rate without anterior prolapse recurrence was 93.8% at 6 years. Compared with baseline, the POP-Q measurements of Aa, Ba, and C points and scores of PFIQ-7 and PFDI-20 manifested significant differences at all times (all p < 0.05). One (5.26%) case of bio-patch-related infection, 1 (5.26%) case of urinary retention, and no exposures and erosion occurred. MRI evaluation showed that the bio-patch gradually degraded to fragments at 1 month and was completely absorbed at 3 months. CONCLUSIONS: Among long-term follow-ups, anterior pelvic reconstruction surgery with a P(LLA-CL)/Fg bio-patch demonstrated significant improvements in anatomical correction of anterior pelvic prolapse and pelvic function without severe morbidity.

Efficacy and safety of olaparib in advanced ovarian cancer: a meta-analysis.

This study aimed to evaluate the efficacy and safety of olaparib for the treatment of advanced ovarian cancer. All studies that assessed the efficacy and safety of olaparib in advanced ovarian cancer were searched in PubMed, Embase, and Web of Science from their inception to 20 September 2022. The analysis included six studies and 2016 patients. Olaparib could significantly prolong the progression-free survival (PFS) of patients compared to that of the control group (HR = 0.49, 95% CI = 0.36 - 0.68). However, no statistically significant differences were detected in overall survival (OS) and objective response rate (ORR) between the olaparib and control groups. Olaparib treatment increased the number of grade ≥3 adverse events (AEs) in patients with advanced ovarian cancer compared with that in the control group. Olaparib significantly prolonged PFS in patients with advanced ovarian cancer; however, no statistically significant differences were detected in OS and ORR. In terms of safety, olaparib has manageable adverse effects.

Tannic acid-loaded hydrogel coating endues polypropylene mesh with hemostatic and anti-inflammatory capacity for facilitating pelvic floor repair.

The application of polypropylene mesh (PPM) in pelvic organ prolapse (POP) treatment was severely limited by the complications associated with PPM, such as mesh exposure, chronic inflammatory reactions and postoperative hematoma. This study applied a method of fabricating a hydrogel-mesh complex (PPM + TA@GelMA) to cross-link tannic acid (TA) directly with Methacrylate Gelatin (GelMA) hydrogel and thus to form a coating for PPM. This one-step coating modification improved the hydrophilicity and cyto-compatibility of PPM. The hemostatic effect of PPM+TA@GelMA was confirmed through tail amputation test. Through the defect tissue repair experiments in vivo, it was proved that PPM+TA@GelMA had effects of anti-inflammation and promoting tissue repair and regulated the M2 subtype macrophages polarization for tissue repair. The TA-loaded hydrogel coating endued PPM with multiple functions. It is believed that the novel hydrogel-mesh complex and its fabrication method will have great significance in basic research and clinical application.

Assessment of Two Formulations of Triptorelin in Chinese Patients with Endometriosis: A Phase 3, Randomized Controlled Trial.

INTRODUCTION: This phase 3, randomized, open-label, active-controlled, multicenter study investigated the efficacy of triptorelin pamoate prolonged-release (PR) 3-month in Chinese patients with endometriosis by demonstrating the noninferiority of the 3-month formulation to the standard of care, triptorelin acetate PR 1-month. METHODS: The trial was conducted in 24 clinical centers in China, and included 300 Chinese women (18-45 years) with endometriosis and regular menstrual cycles who required treatment with a gonadotropin-releasing hormone agonist for 6 months. One group of patients (n = 150) was treated with triptorelin pamoate PR 3-month (15 mg per injection, once every 12 weeks), and the other (n = 150) with triptorelin acetate PR 1-month (3.75 mg per injection, once every 4 weeks). The primary outcome measure was the proportion of patients with estradiol (E2) concentrations suppressed to castration levels (≤ 184 pmol/L, or 50 pg/mL) after 12 weeks of treatment. RESULTS: Triptorelin pamoate PR 3-month was noninferior to triptorelin acetate PR 1-month for the treatment of endometriosis: over 98% of patients in both groups were chemically castrated at week 12. Both formulations were also equally efficacious in reducing endometriosis-associated pelvic pain, and reducing serum concentrations of E2, luteinizing hormone, and follicle-stimulating hormone over time. No new safety concerns were identified. CONCLUSION: Triptorelin pamoate PR 3-month is a valid alternative to triptorelin acetate PR 1-month for the treatment of Chinese women with endometriosis, with fewer injections and a potentially lower burden of care. TRIAL REGISTRATION: NCT03232281.

Comparative evaluation of enema alone and in combination with oral polyethylene glycol for bowel preparation before transvaginal pelvic floor reconstruction in elderly patients: a retrospective cohort study.

The aim of this retrospective study was to assess the value of using an enema alone for mechanical bowel preparation (MBP) before transvaginal pelvic floor reconstruction (TPFR) in patients ≥65 years old. In total, 190 patients were included [81 in the enema group vs. 109 in the enema + polyethylene glycol (PEG) group]. The levels of serum potassium (p = .004) and calcium (p = .005) were higher in the enema group after surgery. The decrease in serum calcium was more significant in the enema + PEG group (p = .027). More patients in the enema + PEG group developed hypokalaemia (p = .035) or hypocalcaemia (p = .008) after surgery. The incidence of thrombus and surgical site infection was similar and earlier bowel movement was evident in the enema group (p = .000). Overall, the enema group used more laxatives (p = .026). Using enema alone before TPFR reduces the incidence of electrolyte disturbances with no increase in surgical complications in elderly patients.IMPACT STATEMENTWhat is already known on this subject? TPFR is an effective treatment for pelvic organ prolapse (POP) in elderly women. Bowel preparation performed before gynecological surgery can reduce surgical site infection, but increase discomfort and electrolyte disturbance.What do the results of this study add? The levels of serum potassium and calcium were lower in the enema + PEG group than in the enema group after surgery and more patients developed hypokalaemia or hypocalcaemia in the enema + PEG group. The incidence of thrombus and surgical site infection was similar between the two groups. Bowel movement was earlier in the enema group.What are the implications of these findings for clinical practice and/or future research? Using enema alone before TPFR reduces the incidence of electrolyte disturbance and does not increase surgical complications. This conclusion needs to be confirmed by random controlled trial studies in the future.

Extracellular vesicle-mediated delivery of miR-127-3p inhibits the proliferation and invasion of choriocarcinoma cells by targeting ITGA6.

BACKGROUND: Choriocarcinoma (CC) is a highly aggressive malignant tumor that mostly occurs in women of childbearing age. Chemotherapy is the main treatment for CC, but it has side effects and causes drug resistance, which can lead to treatment failure. Extracellular vesicles (EVs) that deliver microRNAs (miRNAs) have emerged as a novel and promising therapeutic tool for inhibiting tumor progression and metastasis. This research aimed to study the effects of miR-127-3p-enriched EVs (EV-miR-127-3p) on CC and underlying mechanisms. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to determine the miR-127-3p and integrin subunit alpha-6 (ITGA6) expression levels. The interaction between miR-127-3p and ITGA6 was confirmed by a dual-luciferase reporter assay. Human umbilical cord mesenchymal stem cells (hUCMSCs) were identified using flow cytometry and multilineage differentiation. Uptake of labeled EVs was demonstrated using immunofluorescence staining and flow cytometry assays. EV-miR-127-3p were isolated from the culture medium of hUCMSCs and co-cultured with JEG-3 or JAR cells to evaluate their effects on cell proliferation, invasion, migration, and apoptosis, using the cell counting kit-8, Transwell, and flow cytometry assays. Epithelial-mesenchymal transition (EMT) and the transforming growth factor (TGF)-ß1/Smad pathway were investigated using qRT-PCR and western blotting. RESULTS: The expression of miR-127-3p was downregulated, while that of ITGA6 was upregulated in CC cell lines. ITGA6 was identified as a target gene of miR-127-3p. EV-miR-127-3p could inhibit the proliferation, invasion, migration, and promote the apoptosis of CC cells. We observed that EV-miR-127-3p suppressed EMT of CC cells by targeting ITGA6. In addition, the knockdown of ITGA6 inhibited the TGF-ß1/Smad pathway and reversed the EMT-promoting effect. CONCLUSION: These results indicate that EV-miR-127-3p from hUCMSCs exhibits anti-tumor effects by targeting ITGA6, which may be used as a novel therapeutic strategy for CC treatment.

TPPP3 inhibits the proliferation, invasion and migration of endometrial carcinoma targeted with miR-1827.

OBJECTIVE AND DESIGN: Database screening indicated that tubulin polymerization-promoting protein 3 (TPPP3) was involved in pathogenesis of multiple cancer types. miR-1827 has a potential role in a variety of human cancers. However, the role of TPPP3 and its underlying molecular mechanism in endometrial cancer (EC) has not been investigated. Herein, we aimed to reveal the role of TPPP3/miR-1827 in EC progression. METHODS: Tumour tissue and whole blood samples were collected for the detection of TPPP3 expression. TPPP3 shRNAs and pcDNA-TPPP3 were applied to knockdown or upregulate the TPPP3 expression, and miR-1827 mimic was used to upregulate miR-1827 level. CCK-8 and colony assays were applied to estimate the cell proliferation. Wound healing and Transwell assays were conducted to assess the cell migration and invasion abilities. The dual-luciferase reporter assay was conducted to validate the putative binding site between TPPP3 and miR-1827. Expression of TPPP3, miR-1827 and related proteins in cell lines, tissue and whole blood sample were detected using western blot, RT-qPCR and immunofluorescence. RESULTS: TPPP3 was observed markedly elevated in EC patients and cells. TPPP3 knockdown displayed evident suppression in cell proliferation, migration and invasion in vitro and in vivo. Moreover, we identified TPPP3 as a direct and functional target gene of miR-1827 in EC cells. The miR-1827 induced regulatory effects on EC cells were partially reversed by TPPP3. Additionally, in vivo study confirmed the findings discovered in vitro. CONCLUSION: TPPP3 exerted oncogenic roles in EC progression by sponging miR-1827. This finding might provide potential targets for EC therapy.

Downregulation of hsa_circ_0026123 suppresses ovarian cancer cell metastasis and proliferation through the miR­124­3p/EZH2 signaling pathway.

Circular RNAs (circRNAs) play a role in various types of cancer. The present study suggested that hsa_circ_0026123 expression was upregulated in ovarian cancer (OVA), which was associated with its role in OVA. However, the role of hsa_circ_0026123 in OVA cell invasion and proliferation remains unclear. In the present study, OVA tissues and cell lines were used to investigate the functions of hsa_circ_0026123. The associations between hsa_circ_0026123, miR­124­3p and enhancer of zeste homolog 2 (EZH2) were examined using a luciferase reporter assay. RT­qPCR and western blot analysis were used for gene and protein expression analysis, respectively. Tumor growth was detected using nude mouse tumor xenografts derived from SKOV3 cells, with or without hsa_circ_0026123 downregulation. The results confirmed that hsa_circ_0026123 expression was upregulated in OVA tissues and cell lines, while hsa_circ_0026123 silencing suppressed cell proliferation and migration; it also suppressed the expression of cancer stem cell (CSC) differentiation­related markers in either in vivo or in vitro experiments. The data revealed that hsa_circ_0026123 downregulation suppressed EZH2 expression by miR­124­3p 'sponging', which was confirmed by rescue experiments and luciferase reporter assays. The results revealed that hsa_circ_0026123 silencing suppressed ovarian cancer cell progression via the miR­124­3p/EZH2 signaling pathway. Overall, the findings demonstrated that hsa_circ_0026123 knockdown inhibited OVA cell progression by regulating the miR­124­3p/EZH2 axis. This methodology may thus be used for the targeted therapy of OVA, as well as a candidate biomarker for the diagnosis and treatment of OVA.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse.

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER: NCT03620565, https://register.clinicaltrials.gov.

Periostin Secreted by Carcinoma-Associated Fibroblasts Promotes Ovarian Cancer Cell Platinum Resistance Through the PI3K/Akt Signaling Pathway.

Periostin (POSTN) is a protein secreted by mesenchymal cells. Periostin is upregulated in several cancer types and overexpression is associated with poor prognosis. However, the functional role and molecular underpinnings of periostin in epithelial ovarian cancer (EOC) is unknown. In the present study, periostin was found to be significantly upregulated in EOC stroma. Functional studies revealed that periostin could decrease cisplatin (DDP)-induced apoptosis in EOC. Periostin led to DDP resistance in EOC cells, potentially through the PI3K/Akt signaling pathway. We generated periostin-overexpressing fibroblasts and found that EOC cells were resistant to DDP when co-cultured with periostin-overexpressing fibroblasts. The findings of the present study indicated that periostin secreted by cancer-associated stromal cells may be a potential therapeutic target for EOC.

Safety and efficacy of a self-developed Chinese pelvic repair system and Avaulta repair system for the treatment of pelvic organ prolapse in women: A multicenter, prospective, randomized, parallel-group study.

The pelvic organ prolapse (POP) repair systems used in China are imported and expensive. Our aim was to compare the efficacy and safety of a self-developed pelvic floor repair system versus the Avaulta system.This was a multicenter, randomized, parallel-group, noninferiority trial of 132 patients with POP stage ≥II from the Tongji Hospital Affiliated to Tongji University and the General Hospital of Ningxia Medical University enrolled from 02/2014 to 03/2015. The patients were randomized 1:1 to POP repair using the self-developed system or the Avaulta system. Perioperative conditions, POP quantification, pelvic floor impact questionnaire-7, and prolapse quality of life questionnaires, gynecological ultrasound, and postoperative complications were compared. Patients were followed at 1.5, 3, and 6 months.According to the POP quantification scores obtained at 6 months after surgery, the cure rates of the self-developed and Avaulta groups were 98.3% and 100.0%, respectively (P > .999). At 6 months follow-up, the pelvic floor impact questionnaire-7 scores of the self-developed and Avaulta groups were both improved (P < .001 vs baseline), with no between-group difference observed (P = .488). There were no differences between the 2 groups for subjective symptoms of POP (all P > .05). There were no significant differences between the 2 groups regarding complications (all P > .05).The self-developed pelvic reconstruction system is safe and effective for the treatment of POP and improves the patients' quality of life, without difference compared to the Avaulta system.

Effectiveness and Adverse Events of Early Laparoscopic Therapy versus Conservative Treatment for Tubo-Ovarian or Pelvic Abscess: A Single-Center Retrospective Cohort Study.

BACKGROUND/AIM: We aimed to assess the value of early laparoscopic therapy in management of tubo-ovarian abscess (TOA) or pelvic abscess. METHODS: This was a retrospective study of all consecutive patients who were initially diagnosed with TOA or pelvic abscess at the local hospital between January 2010 and December 2014. The risks of operation and recurrence were analyzed using logistic analyses. RESULTS: The durations of body temperature > 38.0°C (p = 0.001) and hospitalization (p < 0.001) were longer in the conventional group versus the early laparoscopy group. In the conventional group, 15 (50%) patients finally underwent laparoscopic exploration. The abscess size in the late laparoscopic group was significantly larger than the successful antibiotic treatment group (6.3 ± 1.5 vs. 4.9 ± 1.2 cm, p = 0.010). Abscess > 5.5 cm was independently associated with antibiotic failure (OR 4.571; 95% CI 1.612-12.962). Compared with late laparoscopy, early laparoscopy was associated with a shorter operation time (p = 0.037), less blood loss (p = 0.035), and shorter durations of body temperature > 38.0°C (p < 0.001) and hospitalization (p < 0.001). The cost was the lowest in the patients successfully treated conservatively. CONCLUSION: Early laparoscopic treatment is associated with shorter time of fever resolution, shorter hospitalization, and less blood loss compared with conventional treatment for TOA or pelvic abscess.

Extensive profiling of circular RNAs and the potential regulatory role of circRNA-000284 in cell proliferation and invasion of cervical cancer via sponging miR-506.

Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in cervical cancer tumorigenesis is not well understood. The present study aims to investigate the expression profiles and potential modulation of circRNA on cervical cancer carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in cervical cancer cells and circRNA-000284 was identified as one circRNA significantly upregulated in cervical cancer cells. Subsequent mechanistic investigations suggested that knockdown of circRNA-000284 suppressed cell proliferation and invasion, and caused G0/G1 phase cell cycle arrest. By performing anti-AGO2 RNA precipitation and luciferase reporter assay, we identified miR-506 as the circRNA-000284-associated miRNA. Furthermore, Snail-2 was identified as a direct target of miR-506, and circRNA-000284 could positively regulate the expression of Snail-2. Finally, the tumor promoting effect of circRNA-000284 was abolished by co-expression of miR-506 mimics or Snail-2 silencing vector. In conclusion, circRNA-000284 promotes cell proliferation and invasion in cervical cancer, and may serve as a promising therapeutic target for cervical cancer patients. Therefore, silence of circRNA-000284 could be a future direction to develop a novel treatment strategy.

Proportion of Uterine Malignant Tumors in Patients with Laparoscopic Myomectomy: A National Multicenter Study in China.

BACKGROUND: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. METHODS: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. RESULTS: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. CONCLUSIONS: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.