剖宫产术中娩出胎儿前膀胱下推法在凶险性前置胎盘手术中的应用效果

目的评价剖宫产手术时娩出胎儿前膀胱下推法在凶险性前置胎盘手术中的应用效果。方法选择2016年1月至2017年12月安徽医科大学第一附属医院产科收治凶险性前置胎盘孕产妇89例,根据剖宫产时下推膀胱的时机不同,分为A组(47例)与B组(42例),A组为娩出胎儿前膀胱下推组,B组为娩出胎儿后下推膀胱组。比较两组孕产妇一般情况(年龄、孕次、产次、孕周、胎盘植入率)、平均手术出血量、平均输血量、手术时间、术后住院时间、产褥病率、子宫切除、膀胱损伤和新生儿窒息方面的差异。结果 A、B组孕产妇术中出血量分别为(1 927. 76±356. 31) mL、(2 859. 55±477. 80) mL,输血量分别为(861. 72±91. 58) mL、(1 285. 73±162. 69) mL,手术时间分别为(1. 83±0. 87) h、(2. 71±0. 94) h,术后住院时间分别为(5. 37±1. 72) d、(6. 83±1. 56) d,产褥病率分别为10. 64%、28. 57%,子宫切除率分别为14. 89%、35. 71%,新生儿窒息发生率分别为4. 26%、19. 05%,两组差异有统计学意义(P <0. 05)。结论凶险性前置胎盘娩出胎儿前膀胱下推法疗效满意,值得临床推广应用。     

Buformin suppresses proliferation and invasion via AMPK/S6 pathway in cervical cancer and synergizes with paclitaxel

Buformin is an old anti-diabetic agent and manifests potent anti-tumor activities in several malignancies. In the present study, we aimed to explore the functions of buformin in human cervical cancer. As our data shown, buformin exhibited significant anti-proliferative effects in a dose-dependent manner in 4 cervical cancer cell lines. Compared to the control, buformin notably suppressed colony formation and increased ROS production in C33A, Hcc94 and SiHa cells. Flow cytometric analysis showed that buformin induced marked cell cycle arrest but only resulted in mild apoptosis. The invasion of C33A and SiHa cells sharply declined with buformin treatment. Consistently, western blotting showed that buformin activated AMPK and suppressed S6, cyclin D1, CDK4, and MMP9. Moreover, we found that buformin enhanced glucose uptake and LDH activity, increased lactate level, while decreased ATP production in cervical cancer cells. In addition, low doses of buformin synergized with routine chemotherapeutic drugs (such as paclitaxel, cisplatin, and 5-FU) to achieve more significant anti-tumor effects. In vivo, a single use of buformin exerted moderate anti-tumor effects, and the combination with buformin and paclitaxel exhibited even greater suppressive effects. Buformin also consistently showed synergistic effects with paclitaxel in treating primary cultures of cervical cancer cells. Take together, we are the first to demonstrate that buformin suppresses cellular proliferation and invasion through the AMPK/S6 signaling pathway, which arrests cell cycle and inhibits cellular invasion. Buformin also could synergize with routine chemotherapies, producing much more powerful anti-tumor effects. With these findings, we strongly support buformin as a potent choice for treating cervical cancer, especially in combination with routine chemotherapy.     

Poly I:C primes the suppressive function of human palatine tonsil-derived MSCs against Th17 differentiation by increasing PD-L1 expression

It has been established that mesenchymal stem cells (MSCs) can have a suppressive effect on T cells, yet much remains unknown about the underlying mechanisms that support this effect. The T cell co-stimulatory pathway involving the programmed death-1 (PD-1) receptor and its ligand PD-L1 regulates T cell activation, tolerance, and subsequent immune-mediated tissue damage. In this study, human palatine tonsil-derived MSCs (T-MSCs) constitutively expressed PD-L1 and exhibited a suppressive activity that specifically targeted murine Th17 differentiation. Additionally, polyinosinic–polycytidylic acid (poly I:C), a Toll-like receptor 3 (TLR3) ligand, increased PD-L1 expression on T-MSCs. The elevated PD-L1 levels enhanced the suppressive functions of T-MSCs on Th17 differentiation. Therefore, pre-stimulation of T-MSCs with poly I:C may serve as an effective therapeutic priming step for modulating Th17-dominant immune responses.     

Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells

Circulating tumor cells (CTCs), which are captured from blood with anti-epithelial cell adhesion molecule (EpCAM) antibodies, have established prognostic value in specific epithelial cancers, but less is known about their utility for assessing patient response to molecularly targeted agents via measurement of pharmacodynamic (PD) endpoints. We discuss the use of CellSearch (Janssen Diagnostics, LLC, Raritan, NJ) CTC isolation technology for monitoring PD response in early phase trials. We present representative data from three clinical trials with the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) suggesting that CTCs can be used to measure PD effects. However, while often leading to hypothesis-generating information, our experience points to the difficulty in obtaining sufficient EpCAM-expressing CTCs from patients with advanced disease to reach statistically significant conclusions about PD effects from each trial. Overall, the level of phenotypic heterogeneity observed in specimens from patients with advanced carcinomas suggests caution in the use of cell-surface differentiation marker-based methods for isolating CTCs.     

Air pollution and pregnancy outcomes based on exposure evaluation using a land use regression model: A systematic review

This review systematically assessed those studies investigating the association between air pollution and birth outcomes using land use regression (LUR) models for exposure assessment. Fifty-four studies were identified which were published between 2007 and 2019. Most of these were conducted in America, Spain and Canada, while only five were conducted in China. One hundred and ninety-seven LUR models were developed for different pollutants. The main pollutants that these studies assessed were NO₂ and PM_2.5, and the main pregnancy outcomes investigated were preterm birth (PTB), small for gestational age (SGA) and birth weight. Studies consistently found that NO₂ exposure during pregnancy was associated with reduced fetal growth and development. The effect of NO₂ on other adverse pregnancy outcomes is unclear. In addition, it was found that increased PM_2.5 (aerodynamic equivalent diameter ≤ 2.5 um) exposure during pregnancy reduced birth weight. The effect of PM_2.5 on other adverse pregnancy outcomes is also unclear. The relationship between other pollutants and adverse pregnancy outcomes is uncertain based on the existing research. Exposure assessment with LUR modeling has been widely used in Europe and North America, but used less in China. Future studies are recommended to use LUR modeling for individual exposure evaluation in China to better characterize the relationship between air pollution and adverse pregnancy outcomes. In addition, further research is required given that a lot of the associations looked at in the review were inconclusive.