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Long noncoding RNA (lncRNA) cardiac mesoderm enhancer-associated noncoding RNA ( CARMN) is a newly discovered tumor-suppressor lncRNA in cancers. However, its role in cervical cancer (CC) remains elusive. This study was conducted to analyze the molecular mechanism of CARMN in CC cell growth and provide a novel theoretical basis for CC treatment. RT-qPCR and clinical analysis revealed that CARMN and B-cell translocation gene 2 ( BTG2) were downregulated, whereas miR-92a-3p was upregulated in CC tissues and cells and their expressions were correlated with clinicopathological characteristics and prognosis. MTT assay, flow cytometry, and Transwell assays revealed that CARMN overexpression reduced proliferation, migration, and invasion and increased apoptosis rate in CC cells. Mechanically, CARMN repressed miR-92a-3p to promote BTG2 transcription. Functional rescue assays revealed that miR-92a-3p overexpression or BTG2 downregulation reversed the inhibitory role of CARMN overexpression in CC cell growth. Western blot analysis elicited that Wnt3a and β-catenin were elevated in CC cells and CARMN blocked the Wnt/β-catenin signaling pathway via the miR-92a-3p/BTG2 axis. Overall, our findings demonstrated that CARMN repressed miR-92a-3p to upregulate BTG2 transcription and then blocked the Wnt/β-catenin signaling pathway, thereby suppressing CC cell growth.

Objective This study aimed to explore the optimal treatment strategy for International Federation of Gynecology and Obstetrics 2018 stage ⅡB cervical adenocarcinoma patients. Methods cervical adenocarcinoma patients who underwent radical hysterectomy and radical radio-chemotherapy were screened from the clinical diagnosis and treatment for cervical cancer in China database. The 5-year overall survival (OS) and disease-free survival (DFS) were compared using the overall population study and propensity score matching. Results 68 FIGO2018 stage Ⅱ B cervical adenocarcinoma patients were eligible for inclusion. In the overall population study, there was no statistical difference in 5-year OS between the surgery group (n = 41) and the radical radio-chemotherapy group (n = 27), but their DFS was better than that of the radical radio-chemotherapy group (OS: 85.7%vs.62.8%, P = 0.058; DFS: 83.7%vs.59.2%, P = 0.035), the difference was statistically significant. Cox multivariate analysis showed that patients with FIGO2018 stage Ⅱ B cervical adenocarcinoma had worse 5-year OS (HR = 2.036, 95%CI: 0.451–9.21, P = 0.355) and DFS (HR = 1.296, 95%CI: 0.344–5.030, P = 0.708). After 1:1PSM, there were no significant differences in OS and DFS between the surgery group (n = 16) and the radical radio-chemotherapy group (n = 16)(OS: 79.8%vs.92.3%, P = 0.292; DFS: 85.6%vs.68.8%, P = 0.228). Cox multivariate analysis showed that treatment was not an independent risk factor for worse 5-year OS (HR = 0.346, 95%CI: 0.035–3.441, P = 0.365) or DFS (HR = 0.399, 95%CI: 0.075–2.216, P = 0.282). In terms of recurrence after treatment in patients with FIGO2018 stage Ⅱ B cervical adenocarcinoma, the results were consistent before and after matching, and there was no statistical difference between the two groups in terms of recurrence, recurrence time, recurrence site after recurrence. Conclusion For patients with FIGO 2018 stage Ⅱ B cervical adenocarcinoma, radical chemoradiotherapy did not result in better oncology outcome.

The function of root canal sealer was to achieve an appropriate three-dimensional filling effect by filling the root canal and some irregular lumen, thereby inhibiting the residual bacteria. There were many types of sealers, but research to find the most suitable ones was still ongoing. In recent years, researchers had continuously improved the performance of sealers by developing new sealers or adding active ingredients to the sealers. However, most sealers exhibit varying degrees of cytotoxicity and tissue responses, which affect clinical therapy efficacy. This review describes different technical approaches, and recent research progress in the biocompatibility evaluation of root canal sealers and provides brief insights into this field by summarising the performance studies of different root canal sealers.

Cervical cancer with different mutations is associated with specific genomic differences. We developed a new mutation prediction model of the ARHGAP4 gene for cervical cancer.We conducted a panoramic analysis of CESC mutations based on The Cancer Genome Atlas-Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC) database. We made copy number variation analysis and correlation analysis of somatic mutations and tumor mutation load fraction. Then we established a prediction model of ARHGAP4 mutation, screened related genes based on the risk scores, calculated the correlation between the risk score and immune microenvironment, and analyzed drug sensitivity.The prediction model of ARHGAP4 mutation based on mRNA expression is closely related to the survival rate of cervical cancer patients and to the effect of immunotherapy. The prediction model is also related to the infiltration of immune cells and human leukocyte antigen family expression in the immune microenvironment. After computational analysis, three drugs (cytarabine, docetaxel, imatinib) were identified as potential agents for the ARHGAP4 mutation high-risk group, and two drugs (erlotinib, methotrexate) were shown to have therapeutic significance for patients in the low-risk group. The expression of ARHGAP4 was higher in cervical cancer tissues. The proliferation ability of HeLa and SiHa cells decreased after ARHGAP4 knockdown.This study provides not only a new approach for the prediction of the response of the cervical cancer patients to targeted drug therapy but also a new strategy for combining risk stratification with precision treatment.

To develop and validate a deep learning-based pathological risk score (RS) with an aim of predicting patients' prognosis to investigate the potential association between the information within the whole slide image (WSI) and cervical cancer prognosis.A total of 251 patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IA1-IIA2 cervical cancer who underwent surgery without any preoperative treatment were enrolled in this study. Both the clinical characteristics and WSI of each patient were collected. To construct a prognosis-associate RS, high-dimensional pathological features were extracted using a convolutional neural network with an autoencoder. With the score threshold selected by X-tile, Kaplan-Meier survival analysis was applied to verify the prediction performance of RS in overall survival (OS) and disease-free survival (DFS) in both the training and testing datasets, as well as different clinical subgroups.For the OS and DFS prediction in the testing cohort, RS showed a Harrell's concordance index of higher than 0.700, while the areas under the curve (AUC) achieved up to 0.800 in the same cohort. Furthermore, Kaplan-Meier survival analysis demonstrated that RS was a potential prognostic factor, even in different datasets or subgroups. It could further distinguish the survival differences after clinicopathological risk stratification.In the present study, we developed an effective signature in cervical cancer for prognosis prediction and patients' stratification in OS and DFS.

To analyze clinical phenotype and genetic variants in a Chinese pedigree of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome.Whole exome sequencing was carried out for the proband from the pedigree. Suspected FH gene variants were validated by Sanger sequencing. Clinical manifestation and histopathological examination were used to analyze the pedigree comprehensively.The pedigree met the clinical diagnostic criteria for HLRCC syndrome. The whole exome sequencing showed that the FH gene of the proband had a heterozygous missense variant of c.1490TC (p.F497S), which was consistent with the Sanger sequencing. The mother, daughter and son of the proband all had the heterozygous missense variant of c.1490TC (p.F497S). According to the American Society of Medical Genetics and Genomics Classification Standards and Guidelines for Genetic Variations, c.1490TC (p.F497S) (PM2+PP1-M+PP3+PP4) was a possible pathogenic variant. Based on our literature search, this variant was a new variant that had not been reported.The FH gene missense variant of c.1490TC (p.F497S) may be the cause of the HLRCC syndrome pedigree, which provides a basis for the genetic diagnosis and genetic counseling of the HLRCC syndrome.

Processing technology has a significant effect on the functional quality of vegetable oil, but the exact mechanism is not yet very well known so far. The purpose of this study was to investigate the effects of extract methods on the composition and nutrition of peanut oil. Peanut oil was prepared by cold pressing, hot pressing, and enzyme-assisted aqueous extraction, and their trace components were determined by liquid chromatography-mass spectrometry (LC-MS). Serum and liver samples from Sprague-Dawley (SD) rats fed with different extract oils were profiled by gas chromatography-mass spectrometry (GC-MS) and LC-MS. The component analysis showed that different process technologies cause differentiation of trace active ingredients. Metabolomics analysis revealed that a high-fat diet causes serum and hepatic metabolic disorders, which can be ameliorated by hot-pressed and hydroenzymatic peanut oil, including downregulation of partial amino acids, fatty acids, phospholipids, and carbohydrates in cold-pressed peanut oil as well as the upregulation of palmitic acid, uric acid, and pyrimidine in enzyme-assisted aqueous oils. Canonical correspondence analysis (CCA) uncovered strong associations between specific metabolic alterations and peanut oil trace components. The data obtained in this study offers a new insight on the roles of oil processing.

Objective Adenomyosis (AM) is a common gynecological disorder that can cause pelvic pain. The regulatory role of long noncoding RNAs (lncRNAs) in AM progression has been widely reported. This study investigated the effect and mechanism of lncRNA taurine-upregulated gene 1 (TUG1) on endometrial epithelial cells (EECs) in AM. Methods Endometrial tissues of AM patients and controls were collected. A murine model of AM was established by tamoxifen induction. TUG1 expression in endometrial tissues of AM patients and mice was determined. In vivo, the effect of TUG1 on AM mice was measured through H&E staining, Masson’s staining, uterine weight, and estradiol concentration. EECs isolated from AM patients were transfected with sh-TUG1. In vitro, the effect of TUG1 on the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and angiogenesis of EECs was evaluated by CCK8, colony formation, immunofluorescence, wound healing, and Transwell assays. The binding relationship among TUG1, E2F4, and KLF5 was confirmed using RNA immunoprecipitation and RNA pull-down assays. A function rescue experiment was designed to verify the effect of KLF5 on EECs. Results TUG1 expression was elevated in AM mice and patients. Downregulation of TUG1 promoted the recovery of AM mice. Downregulation of TUG1 suppressed proliferation, migration, invasion, EMT, and angiogenesis of EECs. Mechanically, TUG1 suppressed KLF5 transcription by binding to E2F4. Downregulation of KLF5 reversed the inhibitory effect of TUG1 silencing on the functions of EECs. Conclusion TUG1 expression was elevated in AM, and TUG1 facilitated proliferation, migration, invasion, EMT, and angiogenesis of EECs via E2F4/KLF5, thereby aggravating AM.

ObjectiveTo compare the 5-year overall survival (OS) and disease-free survival (DFS) of patients with cervical cancer who received neoadjuvant chemotherapy followed by surgery (NACT) with those who received abdominal radical hysterectomy alone (ARH).MethodsWe retrospectively compared the oncological outcomes of 1410 patients with stage IB3 cervical cancer who received NACT (n=583) or ARH (n=827). The patients in the NACT group were divided into an NACT-sensitive group and an NACT-insensitive group according to their response to chemotherapy.ResultsThe 5-year oncological outcomes were significantly better in the NACT group than in the ARH group (OS: 96.2% vs. 91.2%, respectively, p=0.002; DFS: 92.2% vs. 87.5%, respectively, p=0.016). Cox multivariate analysis suggested that NACT was independently associated with a better 5-year OS (HR=0.496; 95% CI, 0.281-0.875; p=0.015), but it was not an independent factor for 5-year DFS (HR=0.760; 95% CI, 0.505-1.145; p=0.189). After matching, the 5-year oncological outcomes of the NACT group were better than those of the ARH group. Cox multivariate analysis suggested that NACT was still an independent protective factor for 5-year OS (HR=0.503; 95% CI, 0.275-0.918; p=0.025). The proportion of patients in the NACT group who received postoperative radiotherapy was significantly lower than that in the ARH group (pConclusionAmong patients with stage IB3 cervical cancer, NACT improved 5-year OS and was associated with a reduction in the proportion of patients receiving postoperative radiotherapy. These findings suggest that patients with stage IB3 cervical cancer, especially those who are sensitive to chemotherapy, might consider NACT followed by surgery.

Purpose To evaluate the survival outcomes of abdominal Q-M type B and type C2 radical hysterectomy (RH) for early-stage (IA1 (lymphovascular invasion)-IIA2) cervical cancer. Patients and methods Based on this multicenter, retrospective cohort study on the clinical diagnosis and treatment for cervical cancer in China (Four C), the survival outcomes of abdominal type B and type C2 RH for early-stage cervical cancer were compared under real-world and matched cohort study conditions. Results In total, 46,313 cases were included in the Four C database, among whom 20,018 underwent abdominal type B or type C2 RH. In the real-world study, no differences were found in the 5-year overall survival (OS) between the type B group (n=15,471) and type C2 group (n=4547), but the 5-year disease-free survival (DFS) was lower in the type C2 group (82.1 vs 84.8%, hazard ratio: 1.144). Based on the inclusion criteria, 9135 cases were included and the type C2 group (n=1818) was found to have a lower 5-year OS and DFS (OS: 89.5 vs 92.0%, hazard ratio: 1.393; DFS: 84.3 vs 87.4%, hazard ratio: 1.342). Subsequently, 1799 cases from each group were matched and the type C2 group had a lower 5-year DFS (84.6 vs 88.4%, hazard ratio: 1.332). Upon further analysis of the subgroups, the type C2 group had a lower 5-year OS and DFS (OS: 90.3 vs 93.8%, hazard ratio: 1.522; DFS: 85.2 vs 89.4%, hazard ratio: 1.439). Conclusion Q-M type B RH could be used for the treatment of stage IA1 (lymphovascular invasion)-IIA2 cervical cancer.

The human cervical cancer (CC) has been identified as one of the most common tumors in women, and the molecular regulation in CC still remains unclear. The dysregulation of periostin has been found in a variety of cancers, but whether it is involved in the regulation of CC is unknown. The present study aimed to investigate the biological roles of periostin in CC and to explore the potential molecular regulation mechanisms. Here we found that the expression of periostin was overexpressed in CC tissues and CC cell lines (HeLa and SiHa). Knockdown of periostin in HeLa or SiHa cells significantly decreased cell viability, cell migration and invasion, and reduced epithelial-mesenchymal transition (EMT). Moreover, periostin knockdown suppressed the activation of Akt/the mammalian target of rapamycin (mTOR) signaling pathway, which is crucial for periostin to regulate the above biological activities in CC cells. Furthermore, we found that the periostin expression was positively correlated with the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and negatively correlated with the expression of microRNA (miR)-202-3p in CC tissues. We confirmed that MALAT1 positively regulated the expression of periostin by negatively modulating miR-202-3p. In addition, the MALAT1/miR-202-3p/periostin axis was deeply associated with the regulation of the cell viability, cell migration and invasion, and EMT in CC cells. Taken together, these findings suggest that periostin, which can be regulated by the MALAT1-miR-202-3p axis, plays an important role in regulating cell viability, cell migration and invasion, and EMT of CC cells via activating Akt/mTOR signaling.

Recent studies have highlighted that N6-methyladenosine (m6A) plays a significant role in tumorigenicity and progression. However, the mechanism of m6A modifications in the tumor microenvironment (TME) immune cell infiltration in cervical cancer (CC) remains unclear. Clinical and RNA sequencing data of 25 m6A RNA methylation regulators were acquired from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LASSO Cox regression analysis was used to generate a prognostic risk signature. m6A modification patterns were identified based on the expression of 25 m6A regulators, and their correlation with TME immune cell-infiltrating characterization was analyzed. Principal component analysis was used to construct an m6A-scoring signature (m6A score) to evaluate the m6A modification patterns of individual CC samples and guide the selection of more effective immunotherapeutic strategies. Genetic and expression alterations of 25 m6A regulators were highly heterogeneous between CC and normal tissues. METTL14 and IGF2BP1 were selected to conduct the prognostic risk signature. Three m6A modification patterns were identified in 659 CC samples, which were associated with distinct clinical outcomes and biological pathways. The TME immune cell-infiltrating characterization of the three m6A modification patterns was highly consistent with 3 tumor immune phenotypes, including immune-excluded, immune-inflamed, and immune-desert phenotypes. Due to the heterogeneity of m6A modification patterns, an m6A scoring signature was established to evaluate the m6A modification patterns of individual CC samples. Univariate and multivariate Cox regression analyses revealed that the m6A score is a robust and independent prognostic biomarker for assessing the prognosis of CC patients. A low m6A score, characterized by higher somatic mutation and higher expression of proliferation-related and DNA repair-related genes, indicated poor overall survival. Activation of immune infiltration was exhibited by the high m6A score, which was likely to have a good response and clinical benefits to antiPD-1/L1 immunotherapy. This study highlights the prognostic value of 25 m6A regulators in CC. The m6A modification is related to immune regulation and the formation of TME heterogeneity and complexity. An m6A scoring signature to clarify the individual m6A modification pattern could enhance our understanding of TME immune cell-infiltrating characterization and guide immunotherapy strategies.

Objective: Compare the outcomes associated with laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for cervical cancer. Design: Retrospective, multicenter observational analysis Setting: Select patients of LRH and ARH from cervical cancer database and compare their outcomes. Population: Patients with stage IA1 (Lymphovascular space invasion [LVSI]-positive) and stage IIA2 cervical cancer (N=6804) were enrolled, of whom 3003 underwent laparoscopy (LRH group), and 3801 underwent laparotomy (ARH group). Methods: Kaplan-Meier survival analysis,propensity score matching (PSM) and Cox regression. Main Outcome Measures: Five-year overall survival (OS) and 5-year disease-free survival (DFS) Results: Before PSM, there was no difference in outcomes between the groups (5-year OS: LRH 89.2% vs. ARH 90.6%, P=0.903.; 5-year DFS: LRH 84.5% vs. ARH 87.1%, P=0.155). Surgical approach did not affect 5-year OS; however, it did affect 5-year DFS (hazard ratio [HR]=0.827, 95% confidence interval [CI]: 0.711-0.962, P=0.014). After PSM, there was no difference in 5-year OS between the LRH (N=1828) and ARH (N=1828) groups (91.0% vs. 93.1%, P=0.220); but there was a significant difference in 5-year DFS between the LRG and ARH groups (86.2% vs. 90.6%, P=0.002). Cox regression revealed that the surgical approach did not affect 5-year OS; however, it did affect 5-year DFS (HR=0.701, 95% CI: 0.563-0.874, P=0.002). Conclusions: For IA1 (LVSI-positive) and IIA1 cervical cancers, the recurrence rate following laparoscopic surgery was higher than that following open surgery, regardless of the surgeon’s experience.

OBJECTIVE To assess the impact of neoadjuvant chemotherapy on postoperative pathology for stage IB2 and IIA2 cervical squamous cell carcinoma. METHODS Postoperative pathology was compared between patients who received neoadjuvant chemotherapy followed by radical hysterectomy (NACT group) and patients who received upfront radical hysterectomy (URH group). Then, patients in the NACT group were divided into a chemotherapy-sensitive group and a chemotherapy-insensitive group according to their response to chemotherapy. RESULTS After 1:1 propensity score matching (PSM), the positive rates of lymphovascular space invasion (LVSI) (7.9% vs 17.7%, P = 0.001) and cervical deep stromal invasion (60.4% vs 76.2%, P

Adhesion is a postoperative complication that has plagued gynecologists for many years, as 60–90% of gynecological patients develop adhesions after abdominopelvic surgeries. Abdominopelvic adhesions could lead to chronic pelvic pain, infertility, intestinal obstruction, and complicated reoperations. Adhesions might also increase the risk of postoperative chemoradiotherapy failure and endanger patients’ lives, especially after surgeries for gynecological malignant tumors. The aim of this consensus was to review the pathogenesis and clinical consequences of adhesions and to summarize various surgical procedures and preventive measures that can reduce the occurrence of adhesions after gynecological tumor surgeries based on a discussion among well-known domestic gynecology specialists.

Background: Recurrence of the leiomyoma is one of the major concerns of myomectomy in the long-term management, especially for the multiple leiomyomas. Gonadotropin-releasing hormone agonist (GnRHa) is currently one of the most effective medications to reduce the volume of the fibroids and the uterus. However, its role in preventing recurrence after conservative surgery remains unclear. At present, there is no evidence from randomized clinical trials comparing the efficacy between GnRHa and follow-up observation in the recurrence rate of multiple leiomyomas after myomectomy.Methods: We are conducting a randomized controlled trial in women aged 18-45 undergoing myomectomy for the multiple leiomyomas. After the surgery, women whose pathological result confirms multiple leiomyoma are randomized into two parallel groups: observation group and GnRHa group. The primary outcome is the recurrence of either clinical symptoms or imaging.Discussion: The results of this study will provide evidence for the efficacy of the gonadotropin-releasing hormone agonist in preventing the recurrence of high-risk leiomyoma after myomectomy.Trial registration: Chinese Clinical Trial Registry, ChiCTR-IPR-17012992 (http://www.chictr.org.cn/showproj.aspx?proj=21797 ). Registered on 15 Oct 2017.

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BACKGROUND: This study explored the rationality of the 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IIIC for cervical cancer to determine outcomes. METHODS: We conducted a retrospective study of cervical cancer patients who had received radical surgery or Radiotherapy. Multivariate analysis was used to compare 5-year overall survival (OS) and disease-free survival (DFS) for FIGO 2018 stages IIIA, IIIB, and IIIC cervical cancer patients. Based on tumor-node-metastasis (TNM) staging, IIIC cases were divided into 5 subgroups: T1a, T1b, T2a, T2b, and T3. The 5-year OS and DFS of the different IIIC subgroups were further compared using multivariate analysis. RESULTS: (I) The 5-year OS for FIGO 2018 IIIA (n=251), IIIB (n=1,824), and IIIC (n=3,137) were 73.7%, 69.0%, and 74.3%, respectively (P

IntroductionLeiomyoma recurrence is a major concern for long-term myomectomy management, especially for multiple leiomyomas. Gonadotropin-releasing hormone agonist (GnRHa) is one of the most effective medications to reduce the volume of fibroids and the uterus. However, its role in preventing recurrence after conservative surgery remains unclear. At present, there is no randomised clinical trial determining the efficacy of GnRHa treatment for preventing multiple leiomyomas recurrence after myomectomy.Methods and analysisWe are conducting a phase IV randomised controlled trial in women aged 18–45 undergoing myomectomy for multiple leiomyomas. After surgery, women whose pathological result confirms multiple leiomyomas are randomised in a 1:1 ratio into an observation or GnRHa group. The primary outcome is the recurrence of either clinical symptoms or fibroids on imaging. Patients will be assessed for adverse events during the follow-up.Ethics and disseminationThe study was approved by the Medical Ethics Committee of the Tongji Hospital Affiliated with the Tongji Medical College of Huazhong University of Science and Technology (TJ-IRB20180311) according to the submitted study protocol (V.1.0, 10 November 2017) and informed consent (V.1.0, 10 November 2017). The results will be presented at domestic and international conferences and published in peer-reviewed journals.Trial registration numberChiCTR-IPR-17012992.

Background The preservation of fertility and integrity of the reproductive organs has increasingly been of concern to most women with adenomyosis. Adenomyomectomy is conservative surgery that is now widely applied; however, relapse is a serious problem after the operation. Postoperative treatment, such as gonadotropin-releasing hormone agonist (GnRHa) has been suggested to result in reducing the rate of disease recurrence. However, there is still a lack of evidence from randomized clinical trials examining the efficacy of GnRHa in decreasing the postoperative recurrence rate. Method/design Relapse after conservative surgery combined with triptorelin acetate versus conservative surgery only in women with focal adenomyosis is a multicenter, prospective, randomized controlled trial. The primary outcome is relapse assessed using a visual analogue scale (VRS) and numeric rating scale (NRS), pictorial blood loss assessment chart (PBAC) score, and the size of the uterus and the lesion as measured by two/three-dimensional color doppler ultrasonography (2D/3D-CDUS) or magnetic resonance imaging (MRI). The secondary outcomes include quality of life, clinical pregnancy, ovarian reserve, adverse events, assessment by the Short Form (36) Health Survey and Female Sexual Function index, serum follicle-stimulating hormone, estradiol levels, and anti-Muellerian hormone and so on. All these indexes are measured at 3, 6, 12, 18, 24, 30, and 36 months after conservative surgery. Discussion The result of this large, multicenter randomized trial will provide evidence for one of the strategies of long-term management in focal adenomyosis after conservative operation. Trial registration Chinese Clinical Trial Registry: ChiCTR1800014340. Registered on 6 January 2018.

Background: Recurrence of the leiomyoma remains as one of the major concerns of myomectomy in the long-term management, especially for the multiple leiomyomas. Gonadotropin-releasing hormone agonist (GnRHa) is currently one of the most effective medications to reduce the volume of the fibroids and the uterus. However, its role in preventing recurrence after conservative surgery remains unclear. At present, there is no evidence from randomized clinical trials comparing the efficacy between GnRHa and follow-up observation in the recurrence rate of multiple leiomyomas after myomectomy. Methods/design: We are conducting a randomized controlled trial in women aged 18-45 undergoing myomectomy for the multiple leiomyomas. After the surgery, women whose pathological result confirms leiomyoma are randomized into two parallel groups: observation group and GnRHa group. The primary outcome is recurrence of either clinical symptoms or imaging. Discussion: The results of this study will provide evidence for the efficacy of the gonadotropin-releasing hormone agonist in preventing the recurrence of high-risk leiomyoma after myomectomy.

Background Tumor necrosis factor-α (TNF-α) immunotherapy controls the progression of human cervical cancer. Here, we explored the detailed molecular mechanisms played by melatonin in human cervical cancer (HeLa cells) death in the presence of TNF-α injury, with a particular attention to the mitochondrial homeostasis. Methods HeLa cells were incubated with TNFα and then cell death was determined via MTT assay, TUNEL staining, caspase ELISA assay and western blotting. Mitochondrial function was detected via analyzing mitochondrial membrane potential using JC-1 staining, mitochondrial oxidative stress using flow cytometry and mitochondrial apoptosis using western blotting. Results Our data exhibited that treatment with HeLa cells using melatonin in the presence of TNF-α further triggered cancer cell cellular death. Molecular investigation demonstrated that melatonin enhanced the caspase-9 mitochondrion death, repressed mitochondrial potential, increased ROS production, augmented mPTP opening rate and elevated cyt-c expression in the nucleus. Moreover, melatonin application further suppressed mitochondrial ATP generation via reducing the expression of mitochondrial respiratory complex. Mechanistically, melatonin augmented the response of HeLa cells to TNF-α-mediated cancer death via repressing mitophagy. TNF-α treatment activated mitophagy via elevating Parkin expression and excessive mitophagy blocked mitochondrial apoptosis, ultimately alleviating the lethal action of TNF-α on HeLa cell. However, melatonin supplementation could prevent TNF-α-mediated mitophagy activation via inhibiting Parkin in a CaMKII-dependent manner. Interestingly, reactivation of CaMKII abolished the melatonin-mediated mitophagy arrest and HeLa cell death. Conclusions Overall, our data highlight that melatonin enhances TNF-α-induced human cervical cancer HeLa cells mitochondrial apoptosis via inactivating the CaMKII/Parkin/mitophagy axis.

Brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), vascular endothelial growth factor (VEGF) and CD105 are highly expressed in several types of cancer. The present study aimed to determine whether BDNF, TrkB, VEGF and CD105 are associated with the prognosis and metastasis of patients with cervical squamous cell carcinoma (SCC) at the IB2 stage. A total of 79 patients with IB2-stage SCC were enrolled in the present study. The expression levels of BDNF, TrkB, VEGF and CD105 in IB2-stage cervical cancer tissue were detected by immunohistochemistry and their association with clinicopathological indexes or prognostic factors was statistically analyzed. Reverse transcription quantitative PCR was used to detect whether the expression of VEGF was affected in SiHa cells co-cultured with BDNF. In addition, BDNF-induced SiHa cell migration and invasion were examined. BDNF expression in the cervical cancer samples was significantly associated with positive lymphovascular space invasion (P

Background: The surgical experience of surgeons is often considered to affect the oncological outcomes of surgery for cervical cancer, but there is few studies to confirm it. This study aims to analyse the effect of surgical experience of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) before the first LRH on the efficacy of LRH for cervical cancer. Methods:We retrospectively analysed the oncological outcomes of 4024 patients with cervical cancer who received LRH performed by 177 surgeons, whose stages were IA1 with LVSI-IIA2. According to the surgical volume of LRH and ARH before the first LRH, patients treated by surgeons with different LRH experience were divided into six groups: 1-30, 31-60, 61-90, 91-120, 121-180, and ≥181; patients treated by surgeons with different ARH experience were divided into five groups: 0, 1-15, 16-30, 31-80, and ≥81. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate the effect of surgical experience on the oncological outcomes of patients. Findings: In different LRH surgical experience analysis, the 5-year OS fluctuated from 85.5% to 93.3%, and the 5-year DFS fluctuated from 80.9% to 90.1%. After adjusting for case mix with a multivariable analysis, LRH experience was not an independent risk factor for shorter OS or DFS (P = 0.268, P = 0.158). In different ARH surgical experience analysis, the 5-year OS and DFS in the 31-80 group were lower than those in other groups. Previously, 31-80 ARH experience was an independent risk factor for lower OS and DFS (P

The potential of stirring assisted dead-end ultrafiltration (UF) to recover polyphenols from purple sweet potato (PSP) juices was evaluated. For this purpose, the effects of rotation speed (200–600 rpm), transmembrane pressure (TMP) (0.2–0.4 MPa), and membrane molecular weight cut-off (30–100 kDa) were investigated with a lab-scale filtration module. The results showed that the highest protein removal (86%) and polyphenol selectivity (12.2) were both obtained under higher rotation speed (600 rpm). Moreover, filtration flux was more important at 600 rpm due to the anti-fouling effect of shear rate generated by the rotation. The results also revealed that under TMP of 0.4 MPa, the cake resistance was the dominating fouling resistance. In addition, it was shown that the results obtained after fitting the data obtained for the filtration with 100 kDa membranes under the different TMP could be modeled by an exponential model. The optimum UF conditions in this study were found under rotation speed of 600 rpm, using a 100 kDa membrane and at TMP of 0.3 MPa. Six main anthocyanins were identified by HPLC-DAD-ESI-MS2 analysis in the unfiltered PSP juice and the permeate obtained under UF at the optimum conditions, being the intensities of the peaks lower in the filtrate obtained using UF. This study opens the doors of rotation-assisted UF as a promising anti-fouling technique, thus avoiding subsequent purification steps.

MicroRNA-429 (miR-429) has been suggested to inhibit epithelial-mesenchymal transition (EMT), mainly due to targeting of ZEB1 and ZEB2, which are repressors of the cell to cell contact protein, E-cadherin. In this study, we indicated that regulation of miR-429 in cervical cancer cells modulates cell migration, elongation, as well as transforming growth factor β (TGF-β)-induced stress fiber formation through regulating the cytoskeleton reorganization which is likely independent of the zinc finger E-box binding homeobox (ZEB)/E-cadherin axis. ZEB1 and Crk-like adapter protein (CRKL), as novel targets of miR-429 and direct regulators of the actin cytoskeleton were identified. Remarkably, expression levels of ZEB1 and CRKL were inversely associated with the level of miR-429 in cervical cancer cell lines. In addition, individual knockdown and over-expression of these targeting genes phenocopied the roles of miR-429 over-expression and inhibition on cell elongation, migration, stress fiber formation, and invasion. Targeting of ZEB1 by miR-429 led to a decreased expression and transcriptional activity of CRB3, regulated by interference with the translocation of the CRB3. This finally led to decreasing of the expression of Crumbs 3 (CRB3), which is needed for the formation of stress fiber and contractility. Therefore, miR-429 affects cervical cancer by modulating some EMT-related processes. And in this study, evidences were provided to support a role for miR-429 as a novel target suppressing invasion and migration of human cervical cancer cells through modulation of its targeting genes ZEB1 and CRKL. Taken together, our data indicate that miR-429 plays a pivotal role in cervical cancer progression, which is a potential therapeutic target for patients.

Several reports have indicated a role for the members of the G12 family of heterotrimeric G proteins (Gα12 and Gα13) in oncogenesis and tumor cell growth. The aims of the present study were to evaluate the role of G12 signaling in cervical cancer. We demonstrated that expression of the G12 proteins was highly upregulated in cervical cancer cells. Additionally, expression of the activated forms of Gα12/Gα13 but not expression of activated Gαq induced cell invasion through the activation of the RhoA family of G proteins, but had no effect on cell proliferation in the cervical cancer cells. Inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) blocked thrombin-stimulated cell invasion, but did not inhibit cell proliferation in cervical cells, whereas the inhibition of Gαq (RGS2) had no effect. Furthermore, G12 signaling was able to activate Rho proteins, and this stimulation was inhibited by p115-RGS, and Gα12-induced invasion was blocked by an inhibitor of RhoA/B/C (C3 toxin). Pharmacological inhibition of JNK remarkably decreased G12-induced JNK activation. Both a JNK inhibitor (SP600125) and a ROCK inhibitor (Y27632) reduced G12-induced JNK and c-Jun activation, and markedly inhibited G12-induced cellular invasion. Collectively, these findings demonstrate that stimulation of G12 proteins is capable of promoting invasion through RhoA/ROCK-JNK activation.

The traditional inspection method of runoff simulation sequences is based on statistical parameters. While the method can reflect the coincidence of statistical parameters of runoff simulation series and observed data at different time intersections, it ignores the characteristics of runoff as time series (e.g., nonlinearity, dissipation and complexity) which might be required in hydrological engineering. By introducing the concept of sample entropy to quantify complexity, we proposed a new method based on sample entropy and statistical parameters for inspecting random simulation runoff sequences, which can supplement the previous test method. To test the new method, we used the monthly runoff simulation series of Luohe Hydrological Station in Huaihe River Basin, Tanghe Hydrological Station in Yangtze River Basin and Heishiguan Hydrological Station in Yellow River Basin as examples. Our evaluation revealed that this new inspection method can effectively find anomalies (ignored by statistical parameters) about flow value and distribution location of the monthly runoff; and estimate the error values of flow and distribution location in simulation sequences of three basins. Compared to the previous inspection method, this new method can screen out the simulation sequences of higher accuracy more effectively, which offers a new way to improve the accuracy of simulation sequences.

In this study, peanut oil was prepared by cold pressing (temperature under 60 °C), hot pressing (temperature above 105 °C), and enzyme-assisted aqueous extraction technology. Influences of an extraction technology on the oil fatty acid composition and the content of minor bioactive compounds, including tocopherols, polyphenols, and squalene, were investigated in detail. High-fat-diet Sprague-Dawley (SD) rat model was then established to probe the impact of cold-pressed peanut oil (CPO), hot-pressed peanut oil (HPO), and enzyme-assisted aqueous-extracted peanut oil (EAO) on lipid metabolism outcomes, to explore influences of different extraction technologies on lipid functional quality. Results showed that oleic acid was the predominate fatty acid in the EAO (52.57 ± 0.11%), which was also significantly higher (P < 0.05) than CPO and HPO. The HPO showed higher total tocopherol and polyphenol contents (206.84 ± 6.93 mg/kg and 47.87 ± 6.50 mg GA/kg, respectively) than CPO and EAO (P < 0.05). However, the squalene content in CPO was 475.47 ± 12.75 mg/kg, which was the highest among the three oils (P < 0.05). The animal experiment results revealed that EAO could be more prone to induce lipid accumulation in the liver, which may likely to cause nonalcoholic fatty liver disease. However, the serum lipid profiles indicated that the CPO was more beneficial than the EAO and HPO in lowering the serum low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate aminotransferase contents, and increasing the high-density lipoprotein cholesterol content. All of our efforts indicated that an extraction technology can affect the peanut oil lipid fatty acid composition, the bioactive compounds content, and, correspondingly, the lipid metabolism in SD rats.

Numerous studies have indicated that microRNAs (miRs), a group of small non-coding RNAs, are determining regulatory elements involved in the pathogenesis of various types of cancer, including cervical cancer (CC). Although miR-21-5p upregulation has been demonstrated to associate with tumorigenesis by controlling the expression of oncogenic and tumor suppressor genes, only a small number of studies have investigated the expression of miR-21-5p and its functional role in CC. The objective of the present study was to investigate the effect of miR-21-5p on the proliferation, apoptosis, migration and invasion of CC cells, and the potential underlying molecular mechanism of these effects. The measurement of miR-21-5p levels using quantitative polymerase chain reaction revealed that miR-21-5p was markedly increased in CC cell lines compared with normal cells. Upon silencing of miR-21-5p, a marked suppression of the proliferation, migration and invasion of CaSki cells was observed, with induction of cell apoptosis. These effects were reversed with miR-21-5p overexpression. A database search followed by a luciferase reporter assay ascertained that the 3'-untranslated region of the von Hippel-Lindau tumor suppressor (VHL) mRNA sequence was a direct target of miR-21-5p. Furthermore, silencing of VHL neutralized the effects of miR-21-5p inhibition. These observations suggested that miR-21-5p is an oncogene that is able to promote the metastatic phenotype of CC cells through downregulation of VHL expression, which may present a path to novel therapeutic stratagems for the CC therapy.

In the present study, differentially expressed microRNAs (miRNAs) in peritoneal exosomes that were isolated from 10 patients with epithelial ovarian cancer (EOC) with metastasis in the abdominal cavity and 10 participants without cancer (NC) were identified. These differentially expressed miRNAs that were revealed by next-generation sequencing were categorized by Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of their target genes. Notably, two miRNAs that were associated with EOC-miR-149-3p and miR-222-5p-were identified. There were significant differences in expression of miR-149-3p and miR-222-5p between EOC and NC samples, and the effect of the expression level of the two miRNAs on the patient survival was identified using publicly available data from The Cancer Genome Atlas. There is an association between these two miRNAs and EOC, that was further verified by reverse transcription-quantitative polymerase chain reaction in peritoneal exosomes from 10 patients with EOC and NC participants. These results indicated that miR-149-3p and miR-222-5p might be novel biomarkers for evaluating the prognosis of patients with EOC and that these two miRNAs might have potential therapeutic values.

Numerous studies have indicated that microRNAs (miRs), a group of small non-coding RNAs, are determining regulatory elements involved in the pathogenesis of various types of cancer, including cervical cancer (CC). Although miR-21-5p upregulation has been demonstrated to associate with tumorigenesis by controlling the expression of oncogenic and tumor suppressor genes, only a small number of studies have investigated the expression of miR-21-5p and its functional role in CC. The objective of the present study was to investigate the effect of miR-21-5p on the proliferation, apoptosis, migration and invasion of CC cells, and the potential underlying molecular mechanism of these effects. The measurement of miR-21-5p levels using quantitative polymerase chain reaction revealed that miR-21-5p was markedly increased in CC cell lines compared with normal cells. Upon silencing of miR-21-5p, a marked suppression of the proliferation, migration and invasion of CaSki cells was observed, with induction of cell apoptosis. These effects were reversed with miR-21-5p overexpression. A database search followed by a luciferase reporter assay ascertained that the 3′-untranslated region of the von Hippel-Lindau tumor suppressor (VHL) mRNA sequence was a direct target of miR-21-5p. Furthermore, silencing of VHL neutralized the effects of miR-21-5p inhibition. These observations suggested that miR-21-5p is an oncogene that is able to promote the metastatic phenotype of CC cells through downregulation of VHL expression, which may present a path to novel therapeutic stratagems for the CC therapy.

Cervical cancer is the third most commonly diagnosed cancer in women. The human wings apart-like (hWAPL) gene, which is 30,793 bp long and located on 10q23.2., is a human homologue of the WAPL gene in Drosophila melanogaster. hWAPL has the characteristics of an oncogene in uterine cervical cancer. The present study investigated the expression of the hWAPL gene in tissues, including 9 common cancers, consisting of cervical, gastric and lung cancers, liver, bladder, esophageal, endometrial, renal and rectal carcinomas, cervical intraepithelial neoplasia (CIN) and benign squamous epithelia. The immunohistochemical analysis was conducted using paraffin-embedded tissues obtained from 413 patients, consisting of 27 benign squamous epithelial tissue samples, and 47 cervical cancer, 30 cervical intraepithelial neoplasia (CIN)I, 33 CINII, 38 CINIII, 29 gastric cancer, 28 liver carcinoma, 26 bladder carcinoma, 35 esophageal carcinoma, 25 endometrial, 26 renal carcinoma, 36 rectal carcinoma and 33 lung cancer tissues. The expression of hWAPL mRNA was evaluated by reverse transcription-quantitative polymerase chain reaction in 8 benign squamous epithelia and 11 cervical cancer tissues. Compared to benign squamous epithelia and the 8 other cancers, hWAPL protein was significantly increased in cervical cancer (P