Frailty combined with nutritional risk score in predicting postoperative complications of elderly patients with gastrointestinal malignancies.

OBJECTIVE: Exploring the predictive power of frailty combined with nutritional risk on postoperative complications in elderly gastrointestinal malignancies patients. METHODS: Elderly patients who underwent gastrointestinal cancer surgery at Gastrointestinal Surgery Department of the Affiliated Hospital of Binzhou Medical University from August 2021 to June 2022 were selected as the research subjects. The patients' frailty and nutritional status were assessed using the Fried Frailty Scale and the NRS2002 Nutritional Risk Scale within 24 h of admission. Observing and recording the diagnosis and treatment of postoperative complications during the hospitalization. RESULTS: 202 patients were enrolled, including 119 patients (58.91%) with nutritional risk and 89 patients (44.06%) with frailty. Frailty was an independent risk factor for postoperative complications [OR = 5.904, 95%CI (3.103, 11.233)]. The AUC value of frailty assessment was 0.780, which was greater than the AUC value of NRS2002 score of 0.705 (P < 0.01). The AUC value of frailty assessment combined with NRS-2002 score was 0.844, which was significantly higher than that alone (P < 0.01). CONCLUSIONS: The ability of frailty to predict postoperative complications is better than the NRS-2002 score. Frailty combined with nutritional risk assessment can increase the predictive power of postoperative complications in elderly gastrointestinal malignancies patients.

Thermostability of a recombinant G protein-coupled receptor expressed at high level in mammalian cell culture.

Rational design of pharmaceutical drugs targeting integral membrane G protein-coupled receptors (GPCR) requires thorough understanding of ligand binding and mechanism of activation through high resolution structural studies of purified proteins. Due to inherent conformational flexibility of GPCR, stabilization of these proteins solubilized from cell membranes into detergents is a challenging task. Here, we take advantage of naturally occurring post-translational modifications for stabilization of purified GPCR in detergent micelles. The recombinant cannabinoid CB2 receptor was expressed at high yield in Expi293F mammalian cell cultures, solubilized and purified in Façade detergent. We report superior stability of the mammalian cell-expressed receptor compared to its E. coli-expressed counterpart, due to contributions from glycosylation of the N terminus and palmitoylation of the C terminus of CB2. Finally, we demonstrate that the mammalian Expi293F amino acid labelling kit is suitable for preparation of multi-milligram quantities of high quality, selectively stable isotope-labeled GPCR for studies by nuclear magnetic resonance.

Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes.

Exosomes are secreted organelles that have the same topology as the cell and bud outward (outward is defined as away from the cytoplasm) from endosome membranes or endosome-like domains of plasma membrane. Here we describe an exosomal protein-sorting pathway in Jurkat T cells that selects cargo proteins on the basis of both higher-order oligomerization (the oligomerization of oligomers) and plasma membrane association, acts on proteins seemingly without regard to their function, sequence, topology, or mechanism of membrane association, and appears to operate independently of class E vacuolar protein-sorting (VPS) function. We also show that higher-order oligomerization is sufficient to target plasma membrane proteins to HIV virus-like particles, that diverse Gag proteins possess exosomal-sorting information, and that higher-order oligomerization is a primary determinant of HIV Gag budding/exosomal sorting. In addition, we provide evidence that both the HIV late domain and class E VPS function promote HIV budding by unexpectedly complex, seemingly indirect mechanisms. These results support the hypothesis that HIV and other retroviruses are generated by a normal, nonviral pathway of exosome biogenesis.