Molecular Simulation Studies on the Interactions of Bilirubin at Different States with a Lipid Bilayer.

The unconjugated bilirubin (BR) may penetrate through the cell membrane and cause a severe cytotoxicity. However, the molecular mechanism underlying the penetration of BR into the cell membrane is still largely unknown. In this work, we systematically investigate the interaction of BR and a lipid bilayer under different conditions by using all-atom molecular dynamics simulations. It is found that BR at the Z,Z conformation can easily enter into the interior of the lipid bilayer due to its hydrophobicity. However, when BR transforms from the Z,Z conformation to the E,E conformation (after the blue-light emission), its penetration ability is greatly reduced (especially at its ionized state). This study may offer useful physical insights into the effect of phototherapy on the penetration behavior and the cytotoxicity of the unconjugated BR.

Mutational signatures and the genomic landscape of betel quid chewing-associated tongue carcinoma.

Our study presents the genetic landscape betel quid chewing-associated tongue carcinomas (BQ-TCs). We compared the genetic landscape and mutational signatures of 15 BQ-TCs, five nonbetel quid chewing-associated tongue carcinomas (nBQ-TCs), and 82 tongue carcinomas in general population from the TCGA (TCGA-TCs) project. The highlights of this research mainly include: (a) The genetic landscape of BQ-TC was characterized with frequent mutations in RASA1 gene and in CpG islands throughout the genome. (b) The BQ-TC had a distinct mutational signature from that of nBQ-TC and tongue carcinomas in the general population, and this signature was associated with the mutations in RASA1 and in CpG islands. (c) Our study indicates that betel quid (BQ) chewing classifies a distinct group of tongue carcinoma. The BQ chewing might not contribute to the tumorigenesis of tongue carcinomas as a mutagen.

Long-term outcome of thyroid lobectomy for unilateral multifocal papillary carcinoma.

The National Comprehensive Cancer Network (NCCN) guidelines recommend completion thyroidectomy for patients with multifocal papillary thyroid carcinoma (PTC) diagnosed by paraffin pathology after lobectomy. However, studies for the influence of surgical range on prognosis of unilateral multifocal carcinoma are scarce. We analyzed the clinicopathological characteristics and long-term outcomes of patients with unilateral multifocal PTC to identify risk factors for recurrence and disease-related death.The clinical and pathological data of 123 cases with multifocal lesions in the unilateral thyroid lobe were retrospectively collected, including sex, age, stage, surgical range, histopathology characteristics, and follow-up data. The prognostic factors were analyzed by means of the Kaplan-Meier method.The recurrence in the contralateral residual thyroid was observed in 6 cases. The 10-year cumulative recurrence rate of the remnant thyroid was 7.0%. Extrathyroidal extension (ETE) was a significant prognostic factor, with χ equal to 4.043 and a P value of .044. One patient died from progression of pulmonary metastasis during the follow-up. The 10-year disease-specific survival rate was 96% and 14 cases experienced recurrences and underwent a second surgery (11.4%), and thus the 10-year recurrence-free survival rate was 83.2%. Multivariate analysis showed that the pathologic tumor (pT) stage was an independent prognostic factor for the recurrence-free survival rate (P <.0001, hazard ratio 2.871, 95% confidence interval 1.783-4.624).ETE is a significant prognostic factor for the recurrence of the remnant thyroid and pT stage is an independent prognostic factor for tumor recurrence-free survival. Lobectomy (with isthmectomy) is effective for most patients with unilateral multifocal PTC.