Combined hysteroscopic Bigatti shaver (IBS) and resectoscope removal of a heterotopic cesarean scar pregnancy in the first trimester.

OBJECTIVE: To report a case of heterotopic cesarean scar pregnancy reduction using a combined hysteroscopic integrated Bigatti shaver (IBS) and resectoscope with the preservation of a normal gestational sac in the uterine cavity under simultaneous transabdominal ultrasound guidance. DESIGN: Video article. SETTING: University-affiliated hospital. PATIENT: A 30-year-old woman, G5P2A2L2, with two previous cesarean deliveries and a history of fertility problems, was admitted with a heterotopic cesarean scar pregnancy at 7+2 gestational weeks. Ultrasound examination showed a dichorionic diamniotic pregnancy. The first gestational sac (1.7 × 1.7 × 0.6 cm) was located in the previous hysterotomy scars, with a thin layer of myometrium measuring 0.2 cm in thickness and a rich blood supply. The second chorionic sac (2.8 × 2.4 × 1.8 cm) was observed at the uterine fundus. Normal cardiac activity and yolk sacs were observed in both gestational sacs. The couple strongly desired to preserve the intrauterine pregnancy. INTERVENTION(S): After Institutional Review Board approval was obtained, a hysteroscopic IBS combined with a bipolar resectoscope was used to remove the heterotopic cesarean scar pregnancy while preserving the intrauterine gestational sac under simultaneous transabdominal ultrasound guidance. MAIN OUTCOME MEASURE(S): The heterotopic cesarean scar pregnancy was completely resected using hysteroscopy, and the gestational sac in the uterine cavity was successfully preserved. RESULT(S): Trophoblastic tissue was confirmed using histopathological examination. The patient had an unremarkable postoperative recovery. Subsequent serial ultrasonography confirmed a single ongoing pregnancy with normal growth parameters and a normal placental site. CONCLUSION(S): The inability of an IBS to perform coagulation can be offset by its combination with the bipolar resectoscope. Hysteroscopic IBS combined with resectoscope to remove a heterotopic cesarean scar pregnancy offers a short operation time and minimum blood loss. It could be an optimized approach for the management of heterotopic cesarean scar pregnancy in the first trimester when an intrauterine pregnancy needs to be preserved.

Introducing oxygen vacancies to NiFe LDH through electrochemical reduction to promote the oxygen evolution reaction.

The transition metal hydroxide NiFe LDH is a promising oxygen evolution reaction (OER) catalyst. Surface engineering, such as the introduction of oxygen vacancies into NiFe LDH, has been reported to further improve the OER performance; however, searching a facile approach remains an issue. In this work, we report a novel and efficient electrochemical reduction method for in situ introduction of oxygen vacancies into NiFe LDH laminates by applying a constant negative voltage. The results show that the reduced NiFe LDH (denoted as r-NiFe LDH) exhibits enhanced OER performance versus its counterpart NiFe due to the increase of oxygen vacancy density, the electrochemically active surface area, wetting ability, and the significant electron transfer rate. In 1 M KOH, the r-NiFe LDH shows a high current density of 110 mA cm-2 at 1.60 V (vs. RHE), which is 2.8 times the current density of NiFe LDH (40 mA cm-2), as well as the long-term stability of 100 h. This electroreduction method is also applicable to other LDH materials loaded by different current substrates or synthesized by various methods, demonstrating its universality for the enhancement of the OER activity of LDH electrocatalysts.

Aging accelerates while multiparity delays tumorigenesis in mouse models of high-grade serous carcinoma.

OBJECTIVES: The "incessant ovulation" hypothesis links increased risk for tubo-ovarian high-grade serous carcinoma (HGSC) due to more ovulations and reduced risk conferred by pre-menopausal exposures like oral contraceptive use, multiparity, and breastfeeding. However, most women diagnosed with HGSC are postmenopausal, implying age is a major risk factor for HGSC. Our mouse model for HGSC, based on tamoxifen (TAM)-induced somatic inactivation of the Brca1, Trp53, Rb1, and Nf1 (BPRN) tumor suppressor genes in oviductal epithelium, recapitulates key genetic, histopathologic, and biological features of human HGSCs. We aimed to credential the model for future efforts to define biological and risk modification factors in HGSC pathogenesis. METHODS: BPRN mice were treated with TAM to induce tumors at defined ages and parity status. RESULTS: BPRN mice aged 9-months prior to tumor induction had markedly shorter survival than 6-8 week old mice induced to form tumors (median 46.5 weeks versus 61.5 weeks, log-rank test P = 0.0006). No significant differences in cancer phenotypes were observed between multiparous versus nulliparous BPRN mice. However, using a modified tumor model with one wild-type Nf1 allele (BPRNfl/+), nulliparous mice had more advanced tumors than multiparous mice (Mantel-Haenszel Chi-square test of association, P = 0.01). CONCLUSIONS: Our findings show aging is associated with significantly shortened survival post tumor induction in the BRPN model and multiparity delays development and/or progression of HGSC in certain genetic contexts. The findings support relevance of our mouse model to gain mechanistic insights into how known factors exert their protective effects and to test novel approaches for HGSC prevention.

Different expression and localization of aquaporin 7 and aquaporin 9 in granulosa cells, oocytes, and embryos of patients with polycystic ovary syndrome and the negatively correlated relationship with insulin regulation.

OBJECTIVE: To investigate the expression of aquaporin 7 (AQP7) and aquaporin 9 (AQP9) in the granulosa cells of patients with polycystic ovary syndrome (PCOS) and healthy women and detect their localization in oocytes at the germinal vesicle (GV), metaphase I (MI), MII, embryo, and blastocyst stages and the in vitro response to insulin stimulation. DESIGN: Randomized, assessor-blinded study. SETTING: Reproductive medical center. PATIENT(S): A total of 40 women (aged 20-38 years) comprising 29 cases of primary infertility and 11 cases of secondary infertility, of whom 17 had an initial diagnosis of PCOS and three received a PCOS diagnosis after an infertility examination. INTERVENTION(S): Controlling different concentrations of insulin and different treatment times in cultures of normal human granulosa cells in vitro. MAIN OUTCOME MEASURE(S): Expression of AQP7 and AQP9 genes and proteins in granulosa cells detected by real-time quantitative polymerase chain reaction, and localization in oocytes at the GV, MI, MII, embryo, and blastocyst stages by Western blot, immunohistochemical, and immunofluorescence assays, and concentrations of insulin in follicular fluid by enzyme-linked immunosorbent assay. RESULT(S): The expression levels of the AQP7 mRNA and protein in the granulosa cells of patients with PCOS were higher than found in healthy controls. We found AQP7 protein expressed in human oocytes at GV, MI, MII, embryo, and blastocyst stages; it was mainly located in the nucleoplasm. In the PCOS group, the expression level of AQP9 mRNA and protein in granulosa cells was lower, and AQP9 protein was expressed in oocytes at the GV, MI, MII, embryo, and blastocyst stages; it was localized on the nuclear membrane. Compared with healthy women, the insulin expression in patients with PCOS was higher. In cultures of normal human granulosa cells in vitro, the expression of AQP7 and AQP9 mRNA and protein decreased with the increase in insulin concentration; expression statistically significantly decreased when the insulin concentration was 100 nmol/L, and after 6 to 24 hours of exposure the lowest expression levels were found at 12 hours. CONCLUSION(S): The different localization and expression of AQP7 and AQP9 between the two groups suggests that they might be involved in oocyte maturation and embryonic development through different regulatory pathways. The expression levels of AQP7 and AQP9 were negatively correlated with insulin regulation, suggesting that insulin might affect the maturation of PCOS follicles by changing AQP7 and AQP9 expression.

Pelvic incidence: A study of a spinopelvic parameter in MRI evaluation of pelvic organ prolapse.

PURPOSE: This study aims to compare pelvic incidence (PI), a skeletal angle formed by the first sacral vertebrae and femoral heads, in women with and without pelvic organ prolapse (POP) and to explore the correlation of PI with the progression of POP, through 3D reconstruction of MRI scans. METHOD: The case-control study enrolled 48 prolapse patients and 48 paired subjects by collecting and screening clinical information including age, BMI, vaginal deliveries, and levator ani defect scores. PI values were measured in 3D reconstruction models based on MRI scans, and the mean and standard deviation values of PI in both groups were calculated. Receiver operating characteristic (ROC) analysis and logistic regression were used to quantify relationships between PI and prolapse. Additionally, by performing a cross-section study of 69 patients with POP, correlations between PI values and descending vaginal locations were assessed by multivariate linear regression models. RESULTS: Compared with the control group, the patient group has a significantly larger average PI (48.68 ±â€¯10.77˚ vs 42.20 ±â€¯8.55˚, P=0.002). ROC analysis for the classification of prolapse based on PI has an area under the curve of 70.1 % (P < 0.001). Logistic regression identified a larger PI value as a risk factor of prolapse with an odds ratio of 2.90 (95 %CI: 1.46-5.74, P = 0.002) for PI per increasing 10˚. Point Ba and Bp represent the most distal positions of any part of the upper anterior and posterior vaginal walls, respectively. In the patient group, internally, Ba and Bp would descend 0.62 (95 %CI: 0.24-1.00, P=0.002) cm and 0.74 (95 %CI 0.22-1.26, P=0.006) cm for every 10° increase in PI, respectively. The coefficients of the partial correlation of PI for Ba and Bp are 0.381 (P = 0.002) and 0.336 (P = 0.006). CONCLUSIONS: PI is significantly related to morbidity and progression of POP, especially for the anterior and posterior pelvic compartments. As an individual constant value of the spinopelvic skeletal shape, a larger PI value is a risk factor and should be evaluated carefully in medical imaging of POP.

Gene signature characteristic of elevated stromal infiltration and activation is associated with increased risk of hematogenous and lymphatic metastasis in serous ovarian cancer.

BACKGROUND: The clinical significance of hematogenous and lymphatic metastasis in ovarian cancer has been increasingly addressed, as it plays an imperative role in the formation of both intraperitoneal and distant metastases. Our objective is to identify the key molecules and biological processes potentially related to this relatively novel metastatic route in serous ovarian cancer. METHODS: Since lymphovascular space invasion (LVSI) is considered as the first step of hematogenous and lymphatic dissemination, we developed a gene signature mainly based on the transcriptome profiles with available information on LVSI status in the Cancer Genome Atlas (TCGA) dataset. We then explored the underlying biological rationale and prognostic value of the identified gene signature using multiple public databases. RESULTS: We observe that primary tumors with increased risk of hematogenous and lymphatic metastasis highly express a panel of genes, namely POSTN, LUM, THBS2, COL3A1, COL5A1, COL5A2, FAP1 and FBN1. The identified geneset is characterized by enhanced deposition of extracellular matrix and extensive stromal activation. Mechanistically, both the recruitment and the activation of stromal cells, especially fibroblasts, are closely associated with lymphovascular metastasis. Survival analysis further reveals that the elevated expression of the identified genes correlates to cancer progression and poor prognosis in patients with serous ovarian cancer. CONCLUSIONS: Our findings indicate that tumor stroma supports the hematogenous and lymphatic spread of ovarian cancer, increasing tumor invasiveness and ultimately resulting in worse survival. Thus stroma-targeted therapies may improve the clinical outcomes in combination with cytoreductive surgery and chemotherapy.

The Drug Combination of SB202190 and SP600125 Significantly Inhibit the Growth and Metastasis of Olaparib-resistant Ovarian Cancer Cell.

BACKGROUND & OBJECTIVE: Many targeted ovarian cancer patients are resistant to olaparib treatment. Here we seek to understand the underlying molecular events and search for potential combinational therapeutics to surmount the intrinsic olaparib resistance in human ovarian cancer. METHODS: The cytotoxicity was determined by the MTT assay and cell viability was measured using Cell Counting Kit-8 (CCK-8). Protein expressions of ERK, P38, JNK, ERK5, LC3, N-CADHERIN, α-SMA were determined by western blotting. The invasion capacity was evaluated by the transwell chamber. Autophagy flux was monitored by the LC3 puncta formation. The epithelial-mesenchymal transition (EMT) markers were profiled by immunoblotting detection. The in vivo tumor progression was determined by xenograft mice model. RESULTS: The olaparib-resistant cell lines were successfully generated in both SKOV3 and A2780 cells. The proliferative index was significantly higher in resistant cells in comparison with sensitive counterparts in the presence of olaparib. Both P38 and JNK were up-regulated in olaparib-resistant cells. The combinational treatment with P38-specific inhibitor SB202190 and JUN-specific inhibitor SP600125 significantly suppressed cell growth and migration, which was further attributed to the induction of autophagy flux and inhibition of EMT processing. We further consolidated the anti-tumor activities of SB202190 and SP600125 in xenograft mice. CONCLUSION: Our data suggested that aberrant over-expression of P38 and JNK is causally linked to the olaparib resistance in ovarian cancer. Combination of P38 and JUN inhibitors demonstrated significant anti-tumor activity both in vitro and in vivo. Our study highlighted the potential therapeutic value of Mitogen-Activated Protein Kinase (MAPK) inhibitors in olaparib-resistant human ovarian cancer.

miR-181a-5p suppresses invasion and migration of HTR-8/SVneo cells by directly targeting IGF2BP2.

Pre-eclampsia is a pregnancy-related disease that may cause maternal, neonatal and fetal morbidity and mortality and exists in 3-5% of pregnancies worldwide. The discovery of dysregulated microRNAs and their roles in placental development has provided a new avenue for elucidating the mechanism involved in this pregnancy-specific disorder. Here, the roles of human miR-181a-5p, a microRNA that is increased in both the plasma and placenta of severe pre-eclamptic patients, in invasion and migration of trophoblasts were investigated. Ectopic-expression of miR-181a-5p impaired the invasion and migration of HTR-8/SVneo cells, whereas miR-181a-5p inhibition had the opposite effects. IGF2BP2, which harbors a highly conserved miR-181a-5p-binding site within its 3'-UTR, was identified to be directly inhibited by miR-181a-5p. Moreover, siRNAs targeting IGF2BP2 imitated the effects of overexpressed miR-181a-5p on HTR-8/SVneo cell invasion and migration, whereas restoring IGF2BP2 expression by overexpressing a plasmid encoding IGF2BP2 partially reversed the studied inhibitory functions of miR-181a-5p. Thus, we demonstrated here that miR-181a-5p suppresses the invasion and migration of cytotrophoblasts, and its inhibitory effects were at least partially mediated by the suppression of IGF2BP2 expression, thus shedding new light on the roles of miR-181a-5p in the pathogenesis of severe pre-eclampsia.

PNIPAM-MAPOSS Hybrid Hydrogels with Excellent Swelling Behavior and Enhanced Mechanical Performance: Preparation and Drug Release of 5-Fluorouracil.

Poly(N-isopropylacrylamide) (PNIPAM) is a widely-studied polymers due to its excellent temperature sensitivity. PNIPAM-MAPOSS hybrid hydrogel, based on the introduction of acrylolsobutyl polyhedral oligomeric silsesquioxane (MAPOSS) into the PNIPAM matrix in the presence of polyethylene glycol, was prepared via radical polymerization. The modified hydrogels exhibited a thick, heterogeneous porous structure. PEG was used as a pore-forming agent to adjust the pore size. MAPOSS reduced the swelling ratios of gels, and decreased the LCST, causing the hydrogels to shrink at lower temperatures. However, its hydrophobicity helped to improve the temperature response rate. The incorporation of rigid MAPOSS into the polymer network greatly increased the compressive modulus of the hydrogel. It is worth noting that, by adjusting the amount of MAPOSS and PEG, the hydrogel could have both ideal mechanical properties and swelling behavior. In addition, hydrogel containing 8.33 wt % MAPOSS could achieve stable and sustained drug release. Thus, the prepared PNIPAM-MAPOSS hybrid hydrogel can serve as drug carrier for 5-fluorouracil and may have potential application in other biomedical fields.

Effects of PARP-1 inhibitor and ERK inhibitor on epithelial mesenchymal transitions of the ovarian cancer SKOV3 cells.

BACKGROUND: To assess the effects of the poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor PJ34 and ERK1/2 inhibitor U0126 on the proliferation and epithelial mesenchymal transitions (EMT) of cisplatin resistant ovarian cancer SKOV-3 cells. METHODS: Proliferation of SKOV-3 cells was evaluated using a 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide assay with PJ34 and U0126 treatment. Expression changes of E-cadherin and vimentin with PJ34 and U0126 treatment was examined using Western blot and quantitative PCR. In addition, invasion assay was performed in cells treated with PJ34 and U0126. RESULTS: PJ34 and U0126 inhibited proliferation of SKOV-3 cells in a time dependent manner. PJ34 and U0126 suppressed the expression of vimentin and enhanced the expression of E-cadherin. PJ34 and U0126 reduced cell invasion. The inhibitory effects of PJ34 and U0126 were stronger than PJ34 alone. PJ34 inhibited the proliferation and invasion of SKOV-3 cells which can be enhanced by ERK1/2 inhibitor U0126. CONCLUSIONS: These inhibitory effects are partially due to PARP-1 and ERK1/2 mediated attenuation of EMT activity.

shRNA-mediated AMBRA1 knockdown reduces the cisplatin-induced autophagy and sensitizes ovarian cancer cells to cisplatin.

Recent research has revealed a role for Ambra1, an autophagy-related gene-related (ATG) protein, in the autophagic pro-survival response, and Ambra1 has been shown to regulate Beclin1 and Beclin1-dependent autophagy in embryonic stem cells and cancer cells. However, whether Ambra1 plays an important role in the autophagy pathway in ovarian cancer cells is unknown. In this study, we hypothesized that Ambra1 is an important regulator of autophagy and apoptosis in ovarian cancer cells. We firstly confirmed autophagic activity in ovarian cancer OVCAR-3 cells which were treated with cisplatin by assessing endogenous microtubule-associated protein 1 light chain 3 (LC3) localization and the presence of autophagosomes and LC3 protein levels in OVCAR-3 cells. Cell apoptosis and viability were measured by annexin-V and PI staining and MTT assays. We then knocked down Ambra1 expression with transfection with the plasmid expressing the small hairpin RNA (shRNA) targeting AMBRA1, then re-evaluated autophagy in the OVCAR-3 cells subject to cisplatin treatment, and re-determined the sensitivity of OVCAR-3 cells to cisplatin. Results demonstrated that cisplatin treatment induced autophagy in OVCAR-3 cells in association with Ambra1 upregulation in the ovarian cancer cells. When Ambra1 expression was reduced by shRNA, the ovarian cancer cells were more sensitive to cisplatin. In conclusion, Ambra1 is a crucial regulator of autophagy and apoptosis in ovarian cancer cells subject to cisplatin to maintain the balance between autophagy and apoptosis. And the Ambra1-targeting inhibition might be an effective method to sensitize ovarian cancer cells to chemotherapy.