ABSTRACTGenotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment. 相似文献
The stability and efficiency, especially the stability, are generally concerned
issues in Q compensated reverse time migration (Q-RTM). The instability occurs because of the exponentially boosted high frequency ambient noise during the forward
or backward seismic wavefield propagation. The regularization and low-pass filtering
methods are two effective strategies to control the instability of the wave propagation in Q-RTM. However, the regularization parameters are determined experimentally, and the wavefield cannot be recovered accurately. The low-pass filtering method
cannot balance the selection of cutoff frequency for varying Q values, and may damage
the effective signals, especially when the signal-to-noise ratio (SNR) of the seismic data
is low, the Q-RTM will be a highly unstable process. In order to achieve the purpose
of stability, the selection of cutoff frequency will be small enough, which can cause
great damage to the effective high frequency signals. In this paper, we present a stable Q-RTM algorithm based on the excitation amplitude imaging condition, which can
compensate both the amplitude attenuation and phase dispersion. Unlike the existing Q-RTM algorithms enlarging the amplitude, the exponentially attenuated seismic
wavefield will be used during both the forward and backward wavefield propagation
of Q-RTM. Therefore, the new Q-RTM algorithm is relative stable, even for the low
SNR seismic data. In order to show the accuracy and stability of our stable Q-RTM
algorithm clearly, an example based on Graben model will be illustrated. Then, a realistic BP gas chimney model further demonstrates that the proposed method enjoys
good stability and anti-noise performance compared with the traditional Q-RTM with
amplitude amplification. Compare the Q-RTM images of these two models to the reference images obtained by the acoustic RTM with acoustic seismic data, the new Q-RTM
results match the reference images quite well. The proposed method is also tested
using a field seismic data, the result shows the effectiveness of our proposed method. 相似文献
Objective: To report a case of labour induction during extracorporeal membrane oxygenation (ECMO) support in a patient with acute respiratory distress syndrome (ARDS) caused by influenza and review of the literature.
Methods: Case report and the literature search of all English articles on delivery while on ECMO in patients with ARDS caused by influenza.
Results: A 25-year-old pregnant woman was initiated with ECMO due to severe ARDS caused by influenza A (H1N1) virus. When the patient had symptoms of colporrhagia and uterine contractions, the medical team decided to start labour induction while on ECMO. There were in total five case reports identified. Maternal oxygenation was improved after delivery and ECMO was successfully discontinued.
Conclusions: Maternal oxygenation was improved after delivery, which may be beneficial to reduce the duration of ECMO. Caesarean section (CS) may be the most used mode and labour induction could be another option. The procedure should be performed by an experienced ECMO team, cooperating with the obstetrician, anaesthesiologist, and ICU doctors. 相似文献