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Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, is extensively used for clinical therapy in KRAS wild-type colorectal cancer (CRC) patients. However, some patients still cannot get benefit from the therapy, because metastasis and resistance occur frequently after cetuximab treatment. New adjunctive therapy is urgently needed to suppress metastasis of cetuximab-treated CRC cells. In this study, we used two KRAS wild-type CRC cells, HT29 and CaCo2, to investigate whether platycodin D, a triterpenoid saponin isolated from Chinese medicinal herb Platycodon grandifloras, is able to suppress the metastasis of cetuximab-treated CRC. Label-free quantitative proteomics analyses showed that platycodin D but not cetuximab significantly inhibited expression of β-catenin in both CRC cells, and suggested that platycodin D counteracted the inhibition effect of cetuximab on cell adherence and functioned in repressing cell migration and invasion. Western blot results showed that single platycodin D treatment or combined platycodin D and cetuximab enhanced inhibition effects on expressions of key genes in Wnt/β-catenin signaling pathway, including β-catenin, c-Myc, Cyclin D1 and MMP-7, compared to single cetuximab treatment. Scratch wound-healing and transwell assays showed that platycodin D combined with cetuximab suppressed migration and invasion of CRC cells, respectively. Pulmonary metastasis model of HT29 and CaCo2 in nu/nu nude mice consistently showed that combined treatment using platycodin D and cetuximab inhibited metastasis significantly in vivo. Our findings provide a potential strategy to inhibit CRC metastasis during cetuximab therapy by addition of platycodin D. [ABSTRACT FROM AUTHOR]

The hierarchical structure is an ideal nanostructure for conversion-type anodes with drastic volume expansion. Here, we demonstrate a tin-doping strategy for constructing Fe2O3 brushes, in which nanowires with exposed (001) facets are stacked into the hierarchical structure. Thanks to the tin-doping, the conductivity of the Sn-doped Fe2O3 has been improved greatly. Moreover, the volume changes of the Sn-doped Fe2O3 anodes can be limited to ~4% vertical expansion and ~13% horizontal expansion, thus resulting in high-rate performance and long-life stability due to the exposed (001) facet and the unique hierarchical structure. As a result, it delivers a high reversible lithium storage capacity of 580 mAh/g at a current density of 0.2C (0.2 A/g), and excellent rate performance of above 400 mAh/g even at a high current density of 2C (2 A/g) over 500 cycles, which is much higher than most of the reported transition metal oxide anodes. This doping strategy and the unique hierarchical structures bring inspiration for nanostructure design of functional materials in energy storage. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common cancers and is associated with high incidence and mortality rates worldwide. CRC has caused a tremendous loss of human health and wealth. The incidence and mortality of colorectal carcinoma are increasing in young adults. Early cancer detection and prevention are made possible through screening. At present, the faecal immunochemical test (FIT) is a noninvasive method that can be used for the large-scale clinical screening of CRC status. Therefore, this study, based on CRC screening results in Tianjin from 2012 to 2020, was conducted to analyse the major differences in diagnostic performance parameters according to sex and age. Methods: This study was based on 39,991 colonoscopies performed for individuals in the Tianjin CRC screening program from 2012 to 2020. Of these individuals, they had complete FIT and colonoscopy results. The differences in FIT results were analysed by sex and age. Results: According to this study, males were generally more likely to develop advanced neoplasms (ANs) than females, and the prevalence increased with age. Males with negative FIT results were more likely to have advanced neoplasms than females with positive results. The accuracy of the FIT in detecting ANs in each age group was 54.9%, 45.5%, 48.6% and 49.5% in the 40–49, 50–59, 60–69, and ≥ 70 age groups, respectively. Conclusions: The FIT detected ANs with highest accuracy in the 40–49 age group. Our research can provide guidance to formulate CRC screening strategies. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is one of the most common and refractory neurological disorders globally. Ganaxolone, a neuroactive steroid that enhances GABAergic inhibition, has been tested in many trials for the resolution of refractory epilepsy. Based on these, our study implemented a meta‐analysis to evaluate the general benefit of ganaxolone for refractory epilepsy. Methods: EMBASE, Medline, Scopus, Cochrane Library, and Clinicaltrials.gov were searched for relevant randomized controlled trials (RCTs) up to June 20, 2022. The risk ratio (RR) and standard mean difference (SMD) were analyzed using dichotomous and continuous outcomes, respectively with a random effect model. Trial sequential analysis (TSA) was also performed to judge the reliability of results. Results: We totally collected 659 patients from four RCTs to evaluate the efficacy and safety of ganaxolone. As results showed, ≥50% reduction in mean seizure frequency has improved significantly compared with placebo (RR = 1.60, 95%CI: 1.02–2.49, p = 0.04, I2 = 30%), which is supported by TSA. However, the percentage of seizure‐free days shows no statistical significance (p = 0.36). For safety outcomes, adverse events (AEs), serious adverse events, and AE leading to study drug discontinuation all revealed no obvious difference between ganaxolone and placebo (p > 0.05). Significance: Based on our research, we have observed that ganaxolone is safe and has potential efficacy in the treatment of refractory epilepsy, waiting for further studies. [ABSTRACT FROM AUTHOR]

Cold rolling and heat treatment experiments of GH4169 alloy with different deformation were carried out. Effect of different cold rolling deformation and heat treatment state on microstructure and hardness of plate was analyzed. Cold rolling experimental results show that dislocation density is increased, dislocations are cross slipped, deformation texture are enhanced, twins boundaries are decreased and hardness is improved with the increasing of deformation. Different heat treatment experimental results show that when the cold rolling deformation within 0%-20%, after 980 ° C x 10 min solution treatment, the recrystallization is incepted, grains are refined, deformed grains and dislocation are remained in the plate. When the deformation within 0%-20%, deformed grains are remained and recrystallized grain size is refined with the increasing of deformation, thus the hardness of solution treated plate is increased with the increasing of deformation. The recrystallization finished and work hardening is eliminated,thus the hardness of solution treated plate decline to undeformed level and remains unchanged when the deformation larger than 25%. The γ' and γ'' phases are precipitated in the plate after aging heat treatment, and the hardness of the plate is significantly higher than that of the cold rolled and solid solution treatment states, and the hardness is basically not affected by the deformation amount of cold rolling. The threshold value of cold rolling deformation for recrystallization inception of GH4169 alloy is within 5%-10% during 980 ° C solution treatment. And the cold rolling deformation threshold value of complete recrystallization is about 25%. According to actual production condition, the optimal cold rolling deformation is larger than 25%, and the matched solution treatment is 980 ° C x 10 min. [ABSTRACT FROM AUTHOR]