Background Pulmonary arterial hypertension (PAH) is a rare disease in children, with significant mortality. Because of the limited research on pediatric PAH, first, systematic review of related drugs is conducted, and then economic evaluation of PAH drug treatment programs is conducted, which to provide a reference for the choice of more cost‐effective treatment options. Methods The search includes electronic databases such as Pubmed, ScienceDirect, and Embase. Through inclusion and exclusion criteria, screen high‐quality randomized controlled trials. We used TreeAge Pro 2011 software to construct the markov model, that to simulate the total medical cost and quality‐adjusted life years (QALYs), and to calculate the incremental cost‐effectiveness ratio. Sensitivity analysis of transfer probability, utility, and cost was carried out. Results Incorporate two studies that meet the criteria, one compared the therapeutic effects of bosentan and placebo on pediatric PAH, the other compared therapeutic effects of sildenafil and placebo on pediatric PAH, both articles were of good quality. Compared with the sildenafil group (3.38QALYs and $161,120.14), the QALY of the bosentan treatment group (3.33QALYs and $257,411.29) was reduced by 0.05, and the cost increased by $96,291.15. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for sildenafil over bosentan. This dominant result persisted probabilistic analyses. Conclusions Based on this model, a more cost‐effective treatment drug for PAH in children is sildenafil.

Differentiation therapy using small molecules is a promising strategy for improving the prognosis of glioblastoma (GBM). Histone acetylation plays an important role in cell fate determination. Nevertheless, whether histone acetylation in specific sites determines GBM cells fate remains to be explored. Through screening from a 349 small molecule-library, we identified that histone deacetylase inhibitor (HDACi) MS-275 synergized with 8-CPT-cAMP was able to transdifferentiate U87MG GBM cells into neuron-like cells, which were characterized by cell cycle arrest, rich neuron biomarkers, and typical neuron electrophysiology. Intriguingly, acetylation tags of histone 3 at lysine 9 (H3K9ac) were decreased in the promoter of multiple oncogenes and cell cycle genes, while ones of H3K9ac and histone 3 at lysine 14 (H3K14ac) were increased in the promoter of neuron-specific genes. We then compiled a list of genes controlled by H3K9ac and H3K14ac, and proved that it is a good predictive power for pathologic grading and survival prediction. Moreover, cAMP agonist combined with HDACi also induced glioma stem cells (GSCs) to differentiate into neuron-like cells through the regulation of H3K9ac/K14ac, indicating that combined induction has the potential for recurrence-preventive application. Furthermore, the combination of cAMP activator plus HDACi significantly repressed the tumor growth in a subcutaneous GSC-derived tumor model, and temozolomide cooperated with the differentiation-inducing combination to prolong the survival in an orthotopic GSC-derived tumor model. These findings highlight epigenetic reprogramming through H3K9ac and H3K14ac as a novel approach for driving neuron-fate-induction of GBM cells.

This review aimed to assess the quality of available evidence on the economic evaluations of immune checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC) and provide evidence to improve the efficiency of healthcare resources. Materials and Methods: Literature search was performed using some electronic databases (PubMed, Embase and Cochrane Central Register of Controlled Trials). Final search was performed in December 2019. Study characteristics and results were recorded and compared. The quality of the studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklists. We did not elaborate the restrictions on the target population. We included patients with squamous or non-squamous NSCLC and metastatic or advanced cancer. Results: Of 98 papers considered, 21 were chosen for this review. Most of them are costeffectiveness analysis. Comparative regimens consisted of either immune checkpoint inhibitor monotherapy, immune checkpoint inhibitor plus chemotherapy, or chemotherapy alone. Fourteen, four, and three studies were about pembrolizumab, nivolumab, and atezolizumab, respectively. The methods mostly used in these studies were modeling and sensitivity analysis. All studies used quality-adjusted life year (QALY) and life years (LY) as outcomes. Most studies were conducted in high-income countries. Based on the willingness to pay threshold, atezolizumab, and pembrolizumab were found to be cost-effective in one and 10 studies, respectively. None of the studies concluded that nivolumab was cost-effective. For quality assessment, all studies fulfilled more than 50% of the CHEERS checklist. Conclusion: The included studies indicated that pembrolizumab regimens are cost-effective as first-line treatment for patients with NSCLC in developed countries. Nivolumab and atezolizumab are likely to be cost-effective as second-line treatment but not as first-line treatment.

Crack width is the main manifestation of concrete material deterioration. To measure the crack information quickly and conveniently, a non-contact measurement method of concrete planar structure crack based on binocular vision is proposed. Firstly, an improved DeeplabV3+ semantic segmentation model is proposed, which uses L-MobileNetV2 as the backbone feature extraction network, adopts IDAM structure to extract high-level semantic information, introduces ECA attention mechanism, and optimizes the loss function of the model to achieve high-precision segmentation of crack areas. Secondly, the plane space coordinate equation of the concrete structure was constructed based on the principle of binocular vision and SIFT feature point matching, and the crack width was calculated by combining the segmented image. Finally, to verify the performance of the above method, a measurement test platform was built. The experimental results show that the RMSE of the crack measurement by using the algorithm is less than 0.2 mm, and the error rate is less than 4%, which has stable accuracy in different measurement angles. It solves the problem of fast and convenient measurement of the crack width of concrete planar structures in an outdoor environment.

To date, several different types of synthetic genetic switches, including riboregulators, riboswitches, and toehold switches, have been developed to construct AND, OR, NOT, NAND, NOR, and NOT IMPLICATION (NIMP) gates. The logic gate can integrate multiple input signals following a set of algorithms and generate a response only if strictly defined conditions are met. However, there are still some logic gates that have not been implemented but are necessary to build complex genetic circuits. Here, based on the toehold switches and three-way-junction (3WJ) repressors, we designed two novel biological Boolean logic gates of IMPLICATION (IMP) and XOR. Subsequently, the outputs of these two logic gates were characterized by fluorescence analysis, indicating that they can achieve the truth tables of logical gates. Furthermore, the fluorescence intensity under the logical TRUE condition was significantly higher than under the logical FALSE condition, suggesting the high dynamic range of the ON/OFF ratios. Because of the programmability of synthetic RNA switches, the constructed RNA logic gates could serve as elementary units to build a versatile and powerful platform for translational regulation and RNA-based biological computation.