Chronic overload of concentration-dependent iron exerts different effects on ovarian function in C57BL/6J mice†.

Overloaded iron can deposit in the reproductive system and impair ovarian function. But few studies have identified the exact effect of overloaded iron on the endocrine function and fertility capacity in female mice. Here, we established iron-overloaded mouse models by intraperitoneal injection of iron dextran to adult female C57BL/6J mice at 0.1 g/kg (LF group), 0.5 g/kg (MF group), and 1.0 g/kg (HF group) concentrations once a week for eight consecutive weeks. We found that overloaded iron resulted in smaller ovaries, as well as accumulated oxidative damages. The endocrine function and follicle development were also impeded in the MF and HF groups. The 10-month breeding trial indicated that (1) Low concentration of iron (0.1 g/kg) wasn't detrimental to the ovary; (2) Middle concentration of iron (0.5 g/kg) impeded the childbearing process, though it could be recovered following the iron excretion; and (3) High concentration of iron (1.0 g/kg) damaged the fertility, even gave rise to sterility. Yet for those fertile mice, litter number and litter size were smaller and the ovarian reserve of their offspring was impaired. Transcriptome profiling results indicated that overloaded iron could compromise ovarian function by disrupting ovarian steroidogenesis, interfering with ovarian microenvironment, and inhibiting Wnt signaling. Taken together, we have demonstrated the effect that chronic concentration-dependent iron overload exerted on mouse ovarian function, which may act as a preliminary basis for further mechanism and intervention investigations.

Endothelin-1-induced expression of α-smooth muscle actin in human myometrial fibroblasts.

AIM: We aimed to investigate the potential role of endothelin-1 (ET-1) in the regulation of the expression of α-smooth muscle actin (α-SMA) in human myometrial fibroblasts. METHODS: Primary myometrial fibroblasts were obtained from myometrium and were identified by immunocytochemical staining. Then, 1 × 107 cells were treated with ET-1 at a concentration of 0.1, 1.0, 10.0, or 100.0 nM for 24 h. To investigate the time course effects of ET-1 on the growth of fibroblasts, 1 × 107 cells were treated with 10.0 nM ET-1 for 6, 12, 24, and 48 h. Real-time quantitative PCR (qPCR) and Western blot analysis were used to determine the expression of α-SMA mRNA and protein, respectively. RESULTS: Human myometrial fibroblasts were identified by immunohistochemistry. Compared with the control group, the expression levels of α-SMA mRNA and protein were identified in cells treated with ET-1 at a concentration of 0.1, 1.0, 10.0, or 100.0 nM for 24 h (P < 0.05). ET-1 treatment affected the expression of α-SMA mRNA and protein in a dose-dependent manner (P < 0.05). The induction of α-SMA mRNA and protein expression increased from 6 to 48 h. CONCLUSION: The results show that ET-1 induces the expression of α-SMA in human myometrium in vitro.

Silencing nc886, a Non-Coding RNA, Induces Apoptosis of Human Endometrial Cancer Cells-1A In Vitro.

BACKGROUND The role that nc886, a non-coding microRNA, plays in human endometrial cancer is unknown. The present study aimed to describe the functional role of nc886 in human endometrial cancer-1A (HEC-1A) cell line, which may provide another target for human endometrial cancer treatment. MATERIAL AND METHODS The expression levels of nv886 in normal human endometrial tissue and the early phase and late phase of human endometrial cancer tissues were determined and compared by fluorescence in situ hybridization (FISH). Small interference RNA (siRNA) was used to inhibit nc886, and cell proliferation was evaluated with the MTT test. mRNA levels of PKR, NF-κB, vascular endothelial growth factor (VEGF), and caspase-3 were determined against glyceraldehyde 3-phosphate dehydrogenase (GAPDH between the HEC-1A control group and the silenced group (nc886 silenced with siRNA) by real-time reverse transcription polymerase chain reaction (RT-PCR). The protein levels of PKR (total and phosphorylated form), NF-κB, VEGF, and caspase-3 were determined against GAPDH by Western blotting, and cell apoptosis was determined by flow cytometry. RESULTS Our results indicated that a higher level of nc886 was expressed in the late phase of human endometrial cancer tissue, less than in the early phase but still higher than in normal human endometrial tissue. After nc886 was silenced, protein levels of p-PKR (phosphorylated PKR) and caspase-3 were increased, whereas NF-κB and VEGF were decreased. CONCLUSIONS The rate of apoptosis in the silenced group was increased and the rate of cell proliferation was slower in comparison to the control.

Aberrant promoter hypermethylation of p16 gene in endometrial carcinoma.

Previous studies demonstrated that the loss of function of the p16INK4A gene is mainly caused by the hypermethylation of p16 gene promoter; however, whether or not it is associated with the incidence of endometrial carcinoma (EC) remains unclear. In the current study, we conducted a meta-analysis to investigate the effects of p16 gene promoter hypermethylation on the incidence of EC. Detailed research publications were searched from Embase, PubMed, and ISI Web of Knowledge for composition in English or Chinese. The pooled data were collected and analyzed by Review Manager 5.2. Odds ratios (ORs) were calculated and summarized respectively. Six eligible studies, including 261 patients were selected and analyzed. The pooled OR was 0.42, test for overall effect, Z = 10.19, P < 0.0001, indicating that p16 gene promoter hypermethylation was significantly correlated with the EC patients. The results of our study strongly suggest that p16 gene promoter hypermethylation is correlated with an increased risk of EC. P16 gene promoter hypermethylation plays a critical role in endometrial carcinogenesis.

Clinicopathological significance of steroidogenic factor-1 expression in ovarian cancer versus ovarian sex cord stromal tumor.

The significance of steroidogenic factor-1 (SF-1) in human ovarian tumor has not been fully investigated. The purposes of this study are to provide a meta-analysis for SF-1 and to determine whether SF-1 is associated with ovarian tumor progression and clinicopathological characteristics. A detailed literature search was made for related research publications written in English. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, and odds ratio (OR) and corresponding confidence intervals (CIs) were calculated and summarized respectively. Final analysis from seven eligible studies was performed. Aberrant SF-1 expression was significantly lower in ovarian cancer compared to that of normal ovarian tissue (OR = 0.02, 95% CI = 0.00-0.16, p = 0.0002). However, SF-1 protein expression was not significantly different between benign and malignant ovarian tumors (p = 0.35). Interestingly, aberrant SF-1 expression was significantly higher in ovarian sex cord stromal tumors than that of ovarian cancer (OR = 0.00, 95% CI = 0.00-0.01, p < 0.00001). The results of this meta-analysis suggest that SF-1 may play an important role in ovarian cancer initiation and progression. Moreover, SF-1 expression may serve as a marker in the differential diagnosis between ovarian sex cord stromal tumors and ovarian cancer.

Ultrasound-guided high-intensity focused ultrasound vs laparoscopic myomectomy for symptomatic uterine myomas.

STUDY OBJECTIVE: To assess the quality of life (QoL) of women at 1 and 12 months after ultrasound-guided high-intensity focused ultrasound (USgHIFU) treatment as compared with laparoscopic myomectomy for treatment of symptomatic uterine myomas. DESIGN: Nonrandomized prospective clinical trial (Canadian Task Force classification II-2). SETTING: Urban university-based hospital in China. INTERVENTIONS: One hundred thirty premenopausal women underwent USgHIFU (n = 89) or laparoscopic myomectomy (n = 41) for treatment of symptomatic uterine myomas. MEASUREMENTS AND MAIN RESULTS: Eighty-three patients in the HIFU group and 39 in the surgical group were followed up at 1 and 12 months. QoL was assessed using the Medical Outcomes Study 36-Item Short-Form General Health Survey, which showed no significant differences between groups in any of the 8 subscales at the 12-month follow-up visit. Symptom score, willingness to recommend the treatment to a friend, hospital stay, and recovery period were compared between the 2 groups. In the HIFU group, hospital stay was shorter (mean [SD] 2.9 [1.5] days vs 6.2 [2.7] days; p <.001) and patients resumed normal activities sooner (4.5 [1.5] days vs 10.9 [3.8] days; p <.001). Significant clinical complications and adverse events after each treatment were documented and compared, and HIFU yielded significantly better results. CONCLUSIONS: Compared with laparoscopic myomectomy, HIFU treatment of symptomatic uterine myomas leads to comparable QoL and symptom improvement, fewer significant clinical complications and adverse events, shorter hospital stay, and faster recovery. Randomized studies with long-term follow-up are needed to reach definitive conclusions insofar as HIFU treatment of uterine myomas.

Clinical responses to focused ultrasound applied to women with vulval intraepithelial neoplasia.

OBJECTIVES: Focused ultrasound waves penetrate superficial tissues and are aimed toward the target tissues at specific depths to exert their biological effects. Focused ultrasound has been applied for a number of clinical indications, including vulval dystrophies and low-grade vulval disease. This study aimed to assess the efficacy and safety of focused ultrasound treatment of high-grade vulval intraepithelial neoplasia (VIN). METHODS: Eighteen women with high-grade VIN were recruited and treated with focused ultrasound. During each posttreatment follow-up, the safety of, side effects of, and clinical responses to focused ultrasound were evaluated by a standardized protocol, including symptoms, clinical appearance, and histologic findings. RESULTS: All patients completed the designed follow-ups. In most cases, superficial mild to moderate swelling and blisters were seen in the focused ultrasound-treated skin but not in adjacent normal skin. Of the 18 patients, 16 showed complete histologic regression and resolution of symptoms 6 months after treatment. Of the other 2 patients, 1 showed complete regression after a second focused ultrasound treatment. The other patient did not respond to the focused ultrasound treatment and underwent a partial vulvectomy 6 months after treatment. None of the patients developed invasive carcinoma of the vulva during the follow-up period. One patient had local pruritus that was not alleviated by anti-inflammatory medication and local care. CONCLUSIONS: The complete responses observed in women with high-grade VIN treated by focused ultrasound, together with the preservation of adjacent normal tissue, suggest that focused ultrasound may be considered for treatment of high-grade VIN.

Construction and Validation of a Nomogram to Predict the Postoperative Venous Thromboembolism Risk in Patients with HGSOC.

Venous thromboembolism (VTE) is a common complication in patients with high-grade serous ovarian cancer (HGSOC) after surgery. This study aims to establish a comprehensive risk assessment model to better identify the potential risk of postoperative VTE in HGSOC. Clinical data from 587 HGSOC patients who underwent surgical treatment were retrospectively collected. Univariate and multivariate logistic regression analyses were performed to identify independent factors influencing the occurrence of postoperative VTE in HGSOC. A nomogram model was constructed in the training set and further validated in the verification set. Logistic regression identified age (odds ratio [OR] = 1.063, P = .002), tumor size (OR = 3.815, P < .001), postoperative transfusion (OR = 5.646, P = .001), and postoperative D-dimer (OR = 1.246, P = .003) as independent risk factors for postoperative VTE in HGSOC patients. A nomogram was constructed using these factors. The receiver operating characteristic curve showed an area under the curve (AUC) of 0.840 (95% confidence interval [CI]: 0.782, 0.898) in the training set and 0.793 (95% CI: 0.704, 0.882) in the validation set. The calibration curve demonstrated a good consistency between model predictions and actual results. The decision curve analysis indicated the model benefits at a threshold probability of less than 70%. A nomogram predicting postoperative VTE in HGSOC was established and validated. This model will assist clinicians in the early identification of high-risk patients, enabling the implementation of appropriate preventive measures.

WAVE1 gene silencing via RNA interference reduces ovarian cancer cell invasion, migration and proliferation.

OBJECTIVE: Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) has been implicated in cancer cell migration and invasion. We have previously shown that the overexpression of WAVE1 in epithelial ovarian cancer (EOC) tissues is associated with a poor prognosis. However, the mechanism of WAVE1 regulating the malignant behaviors in EOC remains unclear. METHODS: In the present study, we knocked down WAVE1 expression in SKOV3 and OVCAR-3 cells through RNA interference to detect the cell biology and molecular biology changes. Moreover, western-blot was used to investigate the underlying mechanism of WAVE1 regulating the proliferative and invasive malignant behaviors in ovarian cancer cells. RESULTS: The down-regulation of WAVE1 had a significant effect on cell morphological changes. WAVE1 silencing decreased cell migration, cell invasion, cell adhesion, colony formation and cell proliferation in vitro. In addition, we found that down-regulation of WAVE1 inhibited malignant behaviors in vivo. Furthermore, our study also indicated that the PI3K/AKT and p38MAPK signaling pathways might contribute to WAVE1 promotion of ovarian cancer cell proliferation, migration, and invasion. CONCLUSIONS: WAVE1 might promote the proliferative and invasive malignant behaviors through the activation of the PI3K/AKT and p38MAPK signaling pathways in EOC.

Overexpression of c-Abl predicts unfavorable outcome in epithelial ovarian cancer.

OBJECTIVES: Abelson tyrosine kinase (c-Abl) has been shown to promote solid tumor invasion and metastasis. However, little is known regarding whether c-Abl contributes to the development or progression of epithelial ovarian cancer (EOC). The aims of this study are to determine the expression of c-Abl and investigate a possible relationship between c-Abl and prognosis in EOC. METHODS: c-Abl protein level was evaluated in 137 EOC specimens by immunohistochemical staining and 32 EOC specimens by Western blot analysis. Expression of c-Abl in ovarian cancer cell lines was measured by Western blot analysis and immunofluorescence. Survival analysis was performed to assess the correlation between c-Abl expression and survival. RESULTS: Immunohistochemical staining and Western blot analysis revealed that c-Abl was overexpressed in EOC compared with samples from a non-invasive ovarian tumor and normal ovaries (P<0.05). Furthermore, expression of c-Abl was significantly associated with advanced FIGO stage, poor grade, serum Ca-125 and residual tumor size (P<0.05). By Western blot analysis, c-Abl expression was examined in four ovarian cancer cell lines. Meanwhile, immunofluorescence was performed to show c-Abl expression in SKOV3 and 3AO cell lines. Survival analysis demonstrated that patients with low c-Abl staining had a significantly better survival compared to patients with high c-Abl staining (P<0.05). In multivariate analysis, c-Abl overexpression, poor grade, advanced stage and suboptimal surgical debulking were independent prognostic factors of poor survival. CONCLUSIONS: Our present study finds that c-Abl overexpression is associated with an unfavorable outcome. c-Abl may be a crucial predictor for EOC metastasis.

The effect of high-intensity focused ultrasound treatment on immune function in patients with uterine fibroids.

PURPOSE: The aim of this study was to investigate the effect of high-intensity focused ultrasound (HIFU) on immune function in patients with uterine fibroids, in a randomised comparison to conventional myomectomy. METHODS: The patients were assigned (1:1) to the HIFU group or the myomectomy (MY) group. Venous blood samples were collected 24 h before and 24 h and 72 h after operation. The percentages of CD4(+) and CD8(+) T cells and natural killer (NK) cells were quantified by flow cytometry (FCM). Serum levels of interleukin-2 (IL-2), IL-6 and IL-10 were determined using enzyme-linked immunosorbent assay. RESULTS: HIFU was associated with early ambulation, fewer post-operative complications, and shorter hospital stay (p < 0.001). The percentages of CD4(+) and CD8(+) T cells and NK cells in the HIFU group were not significantly altered after treatment compared with before treatment. In contrast, the numbers of these cells in the MY group decreased significantly 24 h after conventional myomectomy (p < 0.001). The CD4(+)/CD8(+) T cell ratios were also decreased significantly 24 h and 72 h after conventional myomectomy (p < 0.001). Serum levels of IL-6 and IL-10 increased after treatment in both groups. Peak IL-6 and IL-10 levels were significantly lower in the HIFU group than in the MY group (p < 0.001). In contrast, IL-2 level decreased significantly in the MY group compared to the HIFU group at 24 h post-operation (p < 0.001). CONCLUSIONS: Short-term post-operative immune function is better preserved after HIFU treatment. Better preserved immune function may reflect a reduction in tissue trauma after HIFU treatment and contribute to reduced post-operative complications.

T-cadherin expression in uterine leiomyoma.

OBJECTIVE: T-cadherin is a tumor-suppressor with low expression in many malignant tumors, but with high expression in endothelial cells and so on. In this study we investigated whether T-cadherin was expressed and if together with bFGF play a role in the occurrence and development of uterine leiomyoma. METHOD: Uterine leiomyoma, the adjacent normal myometrium, control normal myometrium without uterine leiomyoma and vascular features of myoma were collected. Immunohistochemistry, western blot and relative quantitative real time PCR were used to evaluate bFGF and T-cadherin on the three specimens. Data were statistically analysed. RESULTS: T-cadherin was observed on the leiomyoma cellular layers but not in the endochylema, extracellular matrix and leiomyoma vascular endothelial cell, bFGF in the leiomyoma endochylema but not observed in the extracellular matrix and leiomyoma vascular endothelial cell. The protein and mRNA expression of bFGF and T-cadherin in uterine leiomyoma were significantly with higher expression than that in adjacent normal myometrium and control normal myometrium. In addition, T-cadherin correlated well with bFGF. There was relationship between T-cadherin and color Doppler flow imaging (CDFI). CONCLUSION: bFGF and T-cadherin have high expressions in uterine leiomyoma, and T-cadherin is associated with CDFI, indicating that a cross talk between bFGF and T-cadherin plays an important role in the occurrence and development of uterine leiomyoma or even malignant tumors.

Effect of high-intensity focused ultrasound on sexual function in the treatment of uterine fibroids: comparison to conventional myomectomy.

BACKGROUND: Uterine fibroids are the most common benign tumors in women. As a new minimally invasive clinical technology, high-intensity focused ultrasound (HIFU) has been widely applied to the treatment of uterine fibroids, but no study using objective criteria has evaluated the effect of HIFU on sexual function. METHODS: A total of 100 premenopausal patients were enrolled in this randomized clinical trial (RCT). The brief index of sexual functioning (BISF-W) was used to evaluate changes in sexual function. Differences in the outcome were calculated for each individual before treatment and at 3 and 6 months after treatment, and changes were compared between the HIFU group (HIFUG) and the myomectomy group (MYG). RESULTS: Preoperative BISF-W scores were similar in both groups (P < 0.05). No significant differences were found between the two groups at 3 and 6 month after treatment. Within the groups, patients reported less arousal and less problems at 3 month compared to baseline. There was a trend toward improved sexual satisfaction and overall quality of sexual life in both groups 6 months after treatment compared with the baseline, although it failed to reach statistical significance except for the dimensions of relational satisfaction and problems affecting sexuality. CONCLUSIONS: Sexual function improved on average to some degree after both HIFU and conventional myomectomy.

Comparative Survival Outcomes of Hyperthermic Intraperitoneal Chemotherapy, Intraperitoneal Chemotherapy and Intravenous Chemotherapy for Primary Advanced Ovarian Cancer: A Network Meta-Analysis.

OBJECTIVE: We aimed to compare the survival outcomes and adverse events of hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP)and intravenous chemotherapy (IP)for primary advanced ovarian cancer. METHODS: PubMed, CENTRAL (Cochrane Central Registry of Controlled Trials), Embase, Web of Science and Scopus were searched using multiple terms for primary advanced ovarian cancer, including randomized controlled trials and comparative studies in both Chinese and English (up to date 15 August 2022). Outcomes include overall survival, progression-free survival and adverse events. The data were pooled and reported as hazard ratio (HRs) with 95% confidence intervals. The Newcastle-Ottawa Scales were used to assess the risk of bias in the included comparative study. The Cochrane Collaboration's Risk of Bias Tool was used for randomized controlled trials. RESULTS: In total, 32 studies, including 6347 patients and 8 different platinum-based chemotherapy regimens, were included in this network meta-analysis. Our analysis results showed that HIPEC2 (carboplatin with area under the curve 10) exhibited a statistically significant OS benefit compared to IV, weekly dose-dense chemotherapy and HIPEC1 (cisplatin with 75/100 mg/m2). Intraperitoneal plus intravenous chemotherapy was associated with a statistically significantly better likelihood of overall survival compared to IV. For progression-free survival, our statistical results only suggest a better progression-free survival in ovarian cancer patients treated with HIPEC1 compared with weekly dose-dense chemotherapy. No evidence of difference was observed between the other comparison groups. Compared with the non-HIPEC group, HIPEC may had a higher incidence of electrolyte disturbances (≥grade 3). CONCLUSION: Our statistical analysis suggests that the groups receiving HIPEC2 had a better OS than the groups receiving IV, weekly dose-dense chemotherapy and HIPEC1. For PFS, our analysis only showed HIPEC1 is better than IV. Moreover, HIPEC may lead to a higher incidence of electrolyte disturbances (≥grade 3). HIPEC therapy for advanced ovarian cancer is currently controversial.

High level of WAVE1 expression is associated with tumor aggressiveness and unfavorable prognosis of epithelial ovarian cancer.

OBJECTIVES: Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) has been shown to promote cancer invasion and metastasis. However, no evidence has been found to identify the role of WAVE1 in epithelial ovarian cancer (EOC). This study aims to determine the effect of WAVE1 expression and investigate a possible relationship between WAVE1 and prognosis in EOC. METHODS: WAVE1 protein level was measured in 223 EOC specimens by immunohistochemical staining and 46 EOC specimens by Western blot analysis. Expression of WAVE1 in ovarian cancer cell lines was evaluated by Western blot analysis and immunofluorescence. Survival analysis was performed to assess the correlation between WAVE1 expression and survival. RESULTS: Immunohistochemical staining and Western blot analysis showed that WAVE1 was overexpressed in EOC compared with samples from a non-invasive ovarian tumor and normal ovaries (P<0.05). Furthermore, expression of WAVE1 was significantly associated with advanced FIGO stage, poor grade, serum Ca-125 and residual tumor size (P<0.05). By Western blot analysis, WAVE1 expression was detected in four ovarian cancer cell lines. Immunofluorescence was performed to demonstrate WAVE1 expression in SKOV3 and 3AO cell lines. Survival analysis showed that patients with low WAVE1 staining had a significantly better survival compared to patients with high WAVE1 staining (P<0.05). In multivariate analysis, WAVE1 overexpression, advanced stage and suboptimal surgical debulking were independent prognostic factors of poor survival. CONCLUSIONS: Our present study finds that WAVE1 overexpression is associated with an unfavorable prognosis. WAVE1 is an independent prognostic factor for EOC, which suggests that it is a novel and crucial predictor for EOC metastasis.

Transmembrane estrogen receptor GPR30 is more frequently expressed in malignant than benign ovarian endometriotic cysts and correlates with MMP-9 expression.

OBJECTIVE: Molecular studies supporting the idea of malignant transformation of endometriosis are sparse and not well substantiated. The aims of this study were to detect expression levels of the novel estrogen-responsive receptor G protein-coupled estrogen receptor 1 GPER, also termed GPR30, and to determine its correlation with matrix metalloproteinase-9 (MMP-9) in benign and malignant ovarian endometriotic cysts and to explore the significance of GPR30. METHODS: Immunohistochemical staining with the streptavidin-peroxidase method was conducted to determine the expression of GPR30 and MMP-9 in 24 cases of endometriosis-associated ovarian carcinoma (EAOC) and 32 specimens of ovarian endometriosis without malignant transformation. Reverse transcriptase polymerase chain reaction was performed to determine messenger RNA expression of GPR30 and MMP-9 in benign and malignant ovarian endometriotic cysts. We also investigated their associations with known clinic pathological parameters and the interrelationship between the expressions of the 2 proteins. RESULTS: The positive staining ratio of GPR30 was 95.8% (23/24) in EAOC cases, and the HScore was 268; whereas the positive ratio was 25% (8/32) in benign endometriotic cysts, and the Hscore was 95. Matrix metalloproteinase-9 was expressed in all 24 EAOC cases and 87.5% (28/32) of the benign samples, and the Hscores were 280 and 260, respectively (P > 0.05). The receptor GPR30 was significantly higher in EAOCs than in benign endometriotic cysts (P < 0.05). The expression of GPR30 messenger RNA was also significantly higher in malignant ovarian endometriotic cysts than in the benign group. The receptor GPR30 was positively related to tumor size, tumor stage, and lymph node metastasis. A positive relationship between GPR30 and MMP-9 was found (P = 0.002). CONCLUSIONS: The results suggest that the abnormal expression of GPR30 may be involved in malignant transformation, invasion, and metastasis of EAOCs. Testing of GPR30 expression levels may present both diagnostic and therapeutic options for the treatment of ovarian malignancies.

[Doppler flow imaging characteristics of blood supply of uterine fibroids on the therapeutic dosage of ultrasound ablation].

OBJECTIVE: To explore the relationship between therapeutic dosage of ultrasound ablation in treatment of uterine fibroids and imaging characteristics of bloody supply of uterine fibroids by color Doppler ultrasound imaging. METHODS: One hundred and forty-two patients with 168 fibroids were treated by ultrasound ablation. Before treatment, bloody supply of fibroids were classified into grade 0 - 4 by ultrasonography. Three patients lost follow-up with contrast MRI exam within 1 month after treatment, so 165 fibroids were enrolled in this study. Bloody supplies were 9 fibroids in grade 0, 34 fibroids in grade 1, 35 fibroids in grade 2, 55 fibroids in grade 3 and 32 fibroids in grade 4. After 1 month treatment, the treated area without blood supply and ratio of ablation were measured by contrast MRI to evaluate the efficacy of thermal ablation and compare status of blood supple based different therapeutic dosage. According to International Reditherapy for Society (SIR) standard, adverse effect and score of pain were evaluated. RESULTS: (1) Ratio of ablation based: ratios of ablation were 79% in grade 0, 89% in grade 1, 92% in grade 2, 86% in grade 3, 71% in grade 4. It reached statistical difference when blood supply of grade 0 compared with those of grade 2 and 3 (P < 0.05) and blood supply of grade 4 compared with those of grade 1, 2, 3 (P < 0.05). (2) Factor of energy efficiency: factor of energy efficiency were 13.19 J/mm(3) in degree 0, 9.54 J/mm(3) in degree 1, 12.91 J/mm(3) in degree 2, 17.83 J/mm(3) in degree 3 and 28.10 J/mm(3) in degree 4. Factor of energy of ablation in degree 4 was significantly higher than those in degree 1, 2 and 3 blood supply (P < 0.05). It exhibit the positive relationship between blood supply and factor of energy of ablation (r = 0.354, P < 0.01). (3) Score of pain and adverse effect: nearly 85% (120/142) patients could tolerate this treatment very well. Those scores of pain were in range of 0 to 4. All patients did not extend their hospitalization and C to F of SIR standard was not recorded. CONCLUSION: blood supply of myoma measured by ultrasound could predict dosage of ultrasound ablation, it could help select indicated well patients.

Nine Pyroptosis-Related lncRNAs are Identified as Biomarkers for Predicting the Prognosis and Immunotherapy of Endometrial Carcinoma.

BACKGROUND: Endometrial carcinoma (EC) is one of the most common malignancies. Immunotherapy has shown promising effects in the treatment against specific subtypes of EC. METHODS: The RNA and clinical information of patients with EC were acquired from The Cancer Gene Atlas (TCGA) database. Firstly, the differentially expressed pyroptosis-related lncRNAs (PRLs) were screened between the tumor and normal control tissue. Secondly, the PRLs closely related to survival were identified by univariate and multivariate regression analysis, based on which, we evaluated the risk score for each EC patient to construct a risk signature. Moreover, we assessed the prognostic value, clinical relevance immunity, and immunotherapy based on this signature. RESULTS: We screened out 9 individual PRLs (AC087491.1, AL353622.1, AL035530.2, LINC02036, AL021578.1, AL390195.2, AC009097.2, AC004585.1, and AC244517.7) closely related to the prognosis of EC. Kaplan-Meier analyses showed a poorer prognosis for the patients in the high-risk FRLs signature (P < 0.001). The area under the curve (AUC) for 1 year, 2 years, 3 years was 0.693, 0.694, 0.750, respectively. Our risk model could be considered as an independent prognostic marker for EC (P < 0.001, HR:2.172, 95% CI:1.532-3.079). Moreover, immune functions and checkpoints were generally different in the 2 groups. Simulation analysis by termed immunophenoscores hinted that immunotherapy might bring optimal therapeutic effect in the low-risk group. CONCLUSION: We successfully developed a novel signature with 9 lncRNAs related to pyroptosis, which may be used as biomarkers to evaluate the prognosis and immune treatment of EC.

Antiparasitic mebendazole (MBZ) effectively overcomes cisplatin resistance in human ovarian cancer cells by inhibiting multiple cancer-associated signaling pathways.

Ovarian cancer is the third most common cancer and the second most common cause of gynecologic cancer death in women. Its routine clinical management includes surgical resection and systemic therapy with chemotherapeutics. While the first-line systemic therapy requires the combined use of platinum-based agents and paclitaxel, many ovarian cancer patients have recurrence and eventually succumb to chemoresistance. Thus, it is imperative to develop new strategies to overcome recurrence and chemoresistance of ovarian cancer. Repurposing previously-approved drugs is a cost-effective strategy for cancer drug discovery. The antiparasitic drug mebendazole (MBZ) is one of the most promising drugs with repurposing potential. Here, we investigate whether MBZ can overcome cisplatin resistance and sensitize chemoresistant ovarian cancer cells to cisplatin. We first established and characterized two stable and robust cisplatin-resistant (CR) human ovarian cancer lines and demonstrated that MBZ markedly inhibited cell proliferation, suppressed cell wounding healing/migration, and induced apoptosis in both parental and CR cells at low micromole range. Mechanistically, MBZ was revealed to inhibit multiple cancer-related signal pathways including ELK/SRF, NFKB, MYC/MAX, and E2F/DP1 in cisplatin-resistant ovarian cancer cells. We further showed that MBZ synergized with cisplatin to suppress cell proliferation, induce cell apoptosis, and blunt tumor growth in xenograft tumor model of human cisplatin-resistant ovarian cancer cells. Collectively, our findings suggest that MBZ may be repurposed as a synergistic sensitizer of cisplatin in treating chemoresistant human ovarian cancer, which warrants further clinical studies.

[Study on the efficacy and safety of ultrasound ablation in treatment of uterine fibroids].

OBJECTIVE: To investigate the safety and efficacy of ultrasound ablation in treatment of uterine fibroids. METHODS: Ninety-nine patients with 117 leiomyomas in total treated by Haifu JC focused ultrasound tumor therapeutic system were enrolled in prospective and non-randomized clinical trial in First Affiliated Hospital of Chongqing Medical University and Academy of Military Medical Sciences. Ultrasound ablation was performed guided by real-time ultrasonography under conscious sedation for single session. All patients were followed up at 6 months after treatment. On the day of treatment and after 1 month, patients were given by magnetic resonance imaging (MRI) exam to evaluate the effect of fibroids ablation. At 3 and 6 months after treatment, the ratio of ablated area and volume reduction of fibroids more than 50% were evaluated by MRI exam again. The symptoms improvements were evaluated by uterine fibroid symptom (UFS) and complications were analyzed by guideline of society of international radiation (SIR). RESULTS: The average ablated area ratio of the target fibroid was (76 ± 24)%. The average reduction in fibroid volume determined by MRI at 3 and 6 months after treatment was (45 ± 21)% and (59 ± 26)%. Which were significantly decreased than those before treatment (P < 0.05). At 6 months after treatment, 84.6% (99/117) of patients showed more than 50% volume reduction, the rate of improved symptom score was 92% (66/72). All patients could resume normal daily activities at 2 hours after treatment. The adverse reactions of SIR C-D included delayed hospitalization, repeat treatment and increased level of nursing. E-F included permanent sequelae and death. In this study, no adverse reactions of C-F were recorded. Common complications (SIR A-B, only observation or simple management without sequelae) were 35% (35/99). Four cases with adverse reactions B of SIR were found, including 2 cases with skin burning of degree II and 2 cases with febrile, they were administered by symptomatic therapy and changing dressing. The other adverse reaction A of SIR included sorness of buttock, vaginal discharge, dysuria and painful urination, they were only suggested by follow-up. CONCLUSION: It was efficacy and safe that ultrasound ablation as a single strategy were used in treatment of uterine fibroids.