Clinical assessment of prophylactic chemotherapy in treating with hydatidiform mole: A protocol for systematic review and meta-analysis.

BACKGROUND: Hydatidiform mole (HM) is more common as molar pregnancy. It is a disease classified under the category of gestational trophoblastic diseases, which could metastasize after originating in the placenta. A majority of females suffering from molar pregnancies are curable by evacuating retained products of conception and the patient's fertility is preserved. In some cases, the growth perseveres and leads to gestational trophoblastic neoplasia, which is an extremely malicious condition that needs chemo-based treatment. There is a possibility to lessen the risk of gestational trophoblastic disease in females with HM through the administration of prophylactic chemo. Yet, there is controversy regarding prophylactic chemotherapy administered pre-or-post removal of HM to curtail the malignant sequelae. Therefore, we will conduct this research to assess both the efficacy as well as security of using prophylactic chemotherapy to treat HM. METHODS: In the preliminary review, the authors will search for randomized controlled trials involving prophylactic chemotherapy to treat HM. The literature search is carried out in the following electronic databases from their inception to May 2021: Chinese National Knowledge Infrastructure, Chinese BioMedical Literature, and WanFang database are the three Chinese language databases. Web of Science, PubMed, Cochrane Library, and EMBASE are the four English language databases. The authors will also perform a manual search through the bibliographies in related literature to find extra articles and ongoing studies. Two independent authors will assess the literature according to an inclusion criteria, use a specialized data collection table to extract data, and use the Cochrane 'Risk of bias' tool for evaluating any possible bias risk in the selected articles. Data synthesis and statistical operations are completed with the RevMan software (v. 5.3). RESULTS: The present systematic analysis provides a rationalized synthesis of existing evidence related to the use of prophylactic chemotherapy in the treatment of HM. CONCLUSION: Our findings will summarize the current evidences for prophylactic chemotherapy in the treatment of HM. ETHICS AND DISSEMINATION: An ethics approval is nonrequired because pre published results will be used. REGISTRATION NUMBER: DOI 10.17605/OSF.IO/6QV52 (https://osf.io/6qv52/).

G-5555 synergized miR-485-5p to alleviate cisplatin resistance in ovarian cancer cells via Pi3k/Akt signaling pathway.

The present study was meant for the discovery of the underlying functions of miR-485-5p in ovarian cancer concerning cisplatin resistance in vitro. RT-qPCR assessed the miR-485-5p expression in ovarian cancer cell lines, normal cells and cisplatin-resistant Cell line OVCA433-CR. After OVCA433-CR treated with 0,3,5umol/L cisplatin, miR-485-5p expressions were determined. MTT observed the cell cytotoxicity in OVCA433-CR after regulation of miR-485-5p. Targets can predicted the putative binding between miR-485-5p and PAK1 and Luciferase Assay verified this. RT-qPCR decided the inhibitory effect in between. MTT tested the cytotoxicity in different combinations of miR-485-5p and PAK1. Western Blot tested the phosphorylation of Pi3k and Akt in response to miR-485-5p and PAK1 interplay. We evaluated the role of Pi3k/Akt signaling in regulation of miR-485-5p and cisplatin resistance with Wortmannin. miR-485-5p was lower expressed in ovarian cancer cells than normal ones and even lower in OVCA433-CR than OVCA433. As the cisplatin concerntration increased, miR-485-5p decreased. miR-485-5p mimics induced lower cisplatin resistance while miR-485-5p inhibitor caused higher resistance. PAK1 targeted miR-485-5p and inhibited miR-485-5p. PAK1 inhibitor helped to lower the resistance to cisplatin caused by miR-485-5p upregulation. miR-485-5p mimics silenced Pi3k/Akt signaling and PAK1 inhibitor aggravated the silencing. Inhibition of Pi3k/Akt signaling increased miR-485-5p, thereby decreasing the cisplatin-resistance in OVCA433-CR. miR-485-5p decreased cisplatin resistance in ovarian cancer cells via Pi3k/Akt signaling, suggesting that miR-485-5p upregulation might alleviate the cisplatin resistance in ovarian patients.

Pnma5 is essential to the progression of meiosis in mouse oocytes through a chain of phosphorylation.

PNMA (paraneoplastic antigen MA) family includes Pnma1-6. Although other members have been found to be involved in paraneoplastic neurological disorders, death receptor-dependent apoptosis, and tumorigenesis, Pnma5 was thought to be a female fertility factor, as indicated by one genome-wide study. But until now there have not been any further functional studies about Pnma5 in female meiosis. Our preliminary study indicated that Pnma5 might play important roles in meiosis. To further address this, Pnma5 was knocked down in in-vitro maturated (IVM) mouse oocytes, which are common models for mammalian female meiosis, by specific siRNA, and results showed that the loss of Pnma5 significantly delayed the progression of meiosis I and increased chromosome segregation errors during anaphase I. In in-vitro fertilization (IVF), Pnma5 knockdown caused significantly lower fertilization. To assess how it affects meiosis, Pnma5 knockdown was found to significantly decrease the stability of spindle microtubules and altered F-actin organization within actin cap regions, cause significantly abnormal mitochondria aggregation and lower ATP concentration. Next we have found that phosphorylation at Thr533 re-located Pnma5 strongly to spindles & cortex and was required for the phosphorylation of Akt and Gsk3ß, while Src and Erk1/2 phosphorylation was required for the phosphorylation of Pnma5, indicating that phosphorylated Pnma5 is the active form and subsequently activates Akt and Gsk3ß. Collectively this study suggests that Pnma5 is important for meiosis and is the pivot of Src→Erk1/2→Pnma5→Akt→Gsk3ß pathway.

Glycemic variability in normal glucose tolerance women with the previous gestational diabetes mellitus.

BACKGROUND: Women with previous gestational diabetes mellitus (pGDM) and postpartum normal glucose tolerance (NGT) may carry impaired islet ß cell secretion, insulin resistance and subsequent altered glucose homeostasis. And certain normoglycemic groups at risks of diabetes were presented with elevated glycemic variability. The aim of study was to investigate the glycemic variability in NGT women with pGDM. METHODS: Total 48 NGT women with pGDM (pGDM group) and 48 age- and BMI-matched NGT women without pGDM (control group) were recruited in the study. Integrated ß cell function was assessed with the Insulin Secretion-Sensitivity Index-2 (ISSI-2) derived from oral glucose tolerance test. All subjects were monitored using the continuous glucose monitoring system for consecutive 72 h. The multiple parameters of glycemic variability included the mean blood glucose (MBG), standard deviation of blood glucose (SDBG), mean of daily differences (MODD), mean amplitude of glycemic excursions (MAGE) and the incremental areas above preprandial glucose values (AUCpp). RESULTS: The pGDM group had a higher MBG (6.5 ± 0.9 vs. 5.9 ± 0.8 mmol/L, p < 0.05), SDBG (1.3 ± 0.3 vs. 0.9 ± 0.2 mmol/L, p < 0.05), MODD (1.4 ± 0.3 vs. 1.1 ± 0.2 mmol/L, p < 0.05), MAGE (2.7 ± 0.4 vs. 1.8 ± 0.5 mmol/L, p < 0.05), and AUCpp (26.8 ± 3.4 vs. 19.2 ± 3.2 mmol/L·h, p < 0.05), when compared to the control group, and the differences remained significant after adjusting for anthropometric indices and metabolic risk factors. Islet ß cell function index ISSI-2 in the pGDM group was lower than in the control group (p < 0.05). MBG, SDBG, MODD, MAGE and AUCpp were all negatively associated with ISSI-2 in the pGDM group (r = -0.31, -0.30, -0.34, -0.48 and -0.54, respectively, p < 0.05), and the correlations remained significant after adjusting for anthropometric indices and metabolic risk factors. CONCLUSIONS: Normal glucose tolerance women with pGDM were presented with elevated glycemic variability, which may be associated with impaired islet ß cell function.