Tubulin beta eight class VIII (TUBB8) is a subtype of β-tubulin that only exists in primates. Mutations in the TUBB8 gene have been proven to cause oocyte maturation arrest. The aim of this study was to identify the new types of mutations in TUBB8. Six women (families) with oocyte maturation arrest and 100 healthy controls were recruited. The sequence of the TUBB8 gene was amplified and analyzed by Sanger sequencing, which revealed a de novo heterozygous variant c.292G > A (p.G98R) of TUBB8 in one affected individual. This TUBB8 variant was absent in the 100 fertile females and was predicted to be highly damaging to the function of the TUBB8 protein by SIFT and PolyPhen-2. This novel variant extends the spectrum of TUBB8 mutations and the presence of a TUBB8 mutation is being considered to be indicative of a poor prognosis for the success of assisted reproductive treatment.

Overexpression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is commonly observed in various types of tumors. However, the potential mechanism responsible for this molecular event is poorly understood. In the present study, we found that the mRNA levels of WHSC1 were significantly increased in cervical cancer cells, and that CpG sites were almost fully methylated in HaCaT cells, but partially methylated in HeLa and C33A cells. Clinically, the results of quantitative methylation-specific PCR (QMSP) and quantitative real-time PCR (qRT-PCR), showed that methylation levels of the WHSC1 gene were significantly decreased in cervical cancer tumors and inversely correlated with its mRNA expression levels. Both decreased methylation of WHSC1 and increased mRNA were associated with cancer progression and poor prognosis. In addition, overexpression of WHSC1 contributed to cell proliferation, migration and invasion, while cells with WHSC1 knockdown exhibited the opposite effects. AKT/metalloproteinase-2 (MMP-2) signaling was activated and inactivated upon overexpression and silencing of WHSC1, respectively. Silencing of WHSC1 also suppressed tumor growth in a xenograft model. In conclusion, WHSC1 is hypomethylated in cervical cancer, and consequent overexpression of WHSC1 mRNA may promote cervical carcinogenesis by activating the AKT/MMP-2 signaling pathway.

Background/Aim: To summarize the published evidence of prophylactic cefazolin for cesarean delivery given before the procedure versus at cord clamping. Methods: We systematically searched the databases of PubMed, Embase, and CENTRAL in the Cochrane Library for randomized controlled trials that compared prophylactic antibiotics with cefazolin for cesarean delivery given before the procedure versus at cord clamping. Results: Six randomized controlled trials with high quality were included in this meta-analysis. Preoperative administration significantly reduced the risk of postpartum endometritis (RR: 0.57, 95% CI: 0.36-0.90, p = 0.02). Preoperative administration of cefazolin was not associated with a significant reduction in the risk of wound infection (RR: 0.70, 95% CI: 0.43-1.12) and urinary tract infection (RR: 1.19, 95% CI: 0.53-2.63). Furthermore, preoperative administration of cefazolin did not significantly affect proven neonatal sepsis (RR: 0.82, 95% CI: 0.47-1.42), suspected neonatal sepsis that requires a workup (RR: 0.94, 95% CI: 0.72-1.22), or neonatal intensive care unit admissions (RR: 0.90, 95% CI: 0.62-1.28). Conclusion: Pooled results demonstrated that antibiotic prophylaxis with cefazolin for cesarean delivery that is given before skin incision can significantly decrease the incidence of postpartum endometritis.

Our results with maintenance tocolysis with progesterone may be useful for patients who had an episode of threatened preterm labor successfully treated with acute tocolytic therapy.

Metabolism-mediated drug adverse effects (e.g., drug-drug interaction, bioactivation, etc.) strongly limit the utilization of clinical drugs. The present study aims to predict the metabolic capability of cytochrome P450 (CYP) 3A4 toward pazopanib which is an excellent drug exhibiting therapeutic role toward various cancers especially for ovarian cancer. Pazopanib can be well docked into the activity cavity of CYP3A4, and the interaction structure in pazopanib was methyl group located besides nitrogen in the five-membered ring. The distance between the hydrogen atom in methyl group and active center is 3.64 Å. The interaction amino acid is Glu374. Furthermore, both pazopanib and ketoconazole were docked into the activity cavity of CYP3A4 to compare their binding potential. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between pazopanib and activity center of CYP3A4, indicating the easy influence of CYP3A4 inhibitor toward the metabolism of pazopanib. All these data were helpful for the clinical application of pazopanib, and R&D of other tinib drug candidates as new anti-tumor drugs.