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Retinoblastoma (RB) is the most common type of malignant intraocular cancer in teenagers. One of the proteins abnormally expressed during oncogenesis of RB is sonic hedgehog (SHH), which possesses the capability to selectively activate transcription factors of different genes. However, the detailed function of SHH in RB remains unknown. Thus, the present study sought to investigate the role of SHH in the development of RB. The human RB WERI-Rb-1 cell line was used as an in vitro model for the knockdown of SHH by a specific short hairpin RNA (shRNA). To assess the effect of SHH inhibition on cell growth and apoptosis, cell viability, colony formation and flow cytometry assays were conducted. WERI-Rb-1 cells transfected with an shRNA targeting SHH were treated with the phosphoinositide-3 kinase (PI3K)/Akt agonist insulin-like growth factor 1 (IGF-1) to investigate the possible mechanism by which SHH promotes RB. The present results revealed that the silencing of SHH induced G1 cell-cycle arrest and apoptosis in WERI-Rb-1 cells and led to a decrease in cell viability, indicating that SHH has a critical role in the determination of RB cell survival. Moreover, according to the results of the IGF-1 assays, suppression of PI3K/Akt was a prerequisite for SHH inhibition, illuminating its potential role in the treatment of RB. The findings outlined in the present study elucidate a clear link between SHH and the PI3K/Akt pathway in RB cell survival, which could provide valuable inspiration for the advancement of therapies against RB. [ABSTRACT FROM AUTHOR]

Although blood plasma has been used to diagnose diseases and to evaluate physiological conditions, it is not easy to establish a global normal concentration range for the targeting components in the plasma due to the inherent metabolic diversity. We show here that NMR spectroscopy coupled with principal component analysis (PCA) may provide a useful method for quantitatively characterizing the metabolic diversity of human blood plasma. We analyzed 70 human blood plasma samples with and without addition of ibuprofen. By defining the PC score values as diversity index (Idiv) and the drug-induced PC score value change as interaction index (Idist), we find that the two indexes are highly correlated (P < 0.0001). Triglycerides, choline-containing phospholipids, lactate, and pyruvate are associated with both indexes (P < 0.0001), respectively. In addition, a significant amount of lactate and pyruvate are in the NMR "invisible" bound forms and can be replaced by ibuprofen. The diffusion and transverse relaxation time weighted NMR approaches gave rise to a better characterization of the diversity and the interaction than that of the one acquired using NOESYPR1D with 100 ms mixing time. These results might be useful for understanding the blood plasma-drug interaction and personalized therapy. [ABSTRACT FROM AUTHOR]

Background: Upper eyelid retraction is a challenging complication of cosmetic upper eyelid blepharoplasty. To avoid extra trauma, we developed a new technique for correcting iatrogenic upper eyelid retraction by postmigrating a compound flap of the orbicularis muscle and fascia (OFC) on the anterior surface of the tarsal plate. This method extends the aponeurosis of the levator palpebrae superioris muscle (LPS), which can achieve a good correction for post-blepharoplasty retraction. Methods: We collected data from 15 patients with mild to moderate iatrogenic upper eyelid retraction who were treated at our hospital between February 2017 and December 2019. The OFC was used to replace the missing part of the LPS, and post-migration of the LPS and fixation of the OFC to the tarsal margin were conducted. Postoperative outcome measurements included postoperative binocular symmetry, double eyelid smoothness, eyelid fullness, margin reflex distance (MRD1), degree of eyelid closure, and exposure keratitis. The patients were followed-up at seven days, one month, and six months postoperatively. Results: One patient with moderate eyelid retraction showed undercorrection 6 months postoperatively, with the upper eyelid margin located at the upper edge of the pupil. The remaining patients had the upper eyelid margin stabilized at 1.0--2.0 mm below the upper corneal margin. Other observational indicators were satisfactory, including binocular symmetry, double eyelid fluency, and eyelid fullness. During the follow-up, no exposure keratitis was identified. The MRD1 indexes after the operation were significantly different (P<0.001) from those before the procedure. Conclusions: Extension and post-migration of the LPS using the orbicularis muscle and OFC structure can effectively correct mild iatrogenic eyelid retraction after ptosis with less damage and good postoperative eyelid morphology and closure function. [ABSTRACT FROM AUTHOR]

A new strategy for determining the Hg isotopes in low Hg concentration samples is proposed, utilizing the flow injection plasma electrochemical vapor generation (FI-PEVG) sampling technique coupled with MC-ICPMS. Our study reveals that PEVG technology not only offers superior sensitivity compared to that achieved by conventional cold vapor generation (CVG), but also reduces potential interferences/contaminations arising from reagents as it avoids the use of SnCl2, thus greatly facilitating the analysis of low content samples. By integrating with the FI technique, we can decrease the required sample volume to 0.15 mL (1.5 ng) and shorten the analysis time to just 150 s, resulting in significant reductions in sample consumption and analysis time. Different parameters affecting Hg isotope measurements were optimized, and the linear regression slope method was selected to process the transient Hg isotope signals. Under the optimized conditions, the δ202Hg and Δ199Hg values achieved a precision of 0.05‰ and 0.04‰ (SD, n = 33), respectively. The efficacy of our strategy is demonstrated by analyzing spiked natural water samples and two reference materials (GBW 08617 and GBW(E) 080124). Although a small number of low Hg concentration samples have been analyzed in this study, it is believed that the proposed method provides a promising rapid and sensitive approach for accurate Hg isotope analysis of low-content samples. [ABSTRACT FROM AUTHOR]

Infrared radiation count (IRC) is considered as an indicator for damage evolution of rocks. This new indicator links damage intensity and corresponding infrared radiation temperature. As demonstrated exemplary for sandstone, the sudden change of IRC can be considered as a damage indicator for rocks under loading. All samples showed IRC sudden changes around the peak stress, and 75% of the samples showed sudden changes before reaching the peak stress. Therefore—considering that infrared camera covers only about 25% of sample surface—IRC can be used as an early warning signal for rock failure. IRC variations are mainly related to energy release during the energy transformation process from elastic strain energy into fracture energy, heat and seismic energy. IRC is randomly distributed over the whole sample surface with very low values in the quasi-elastic deformation stage, but with the onset of local cracking, sudden and significant changes occur. The use of IRC as a nondestructive failure precursor in laboratory tests is recommended. [ABSTRACT FROM AUTHOR]