Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study.

BACKGROUND: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. METHODS: Prospectively collected data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analyzed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×10 3  U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. RESULTS: The normal group ( n =179 patients) and the normalization group ( n =73 patients) had better OS and RFS than the non-normalization group ( n =65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P <0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P =0.255; RFS, P =0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P =0.025; RFS, P =0.003). CONCLUSIONS: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Computational Exploration of Dirhodium Complex-Catalyzed Selective Intermolecular Amination of Tertiary vs. Benzylic C-H Bonds.

The mechanism and origins of site-selectivity of Rh2(S-tfpttl)4-catalyzed C(sp3)-H bond aminations were studied using density functional theory (DFT) calculations. The synergistic combination of the dirhodium complex Rh2(S-tfpttl)4 with tert-butylphenol sulfamate TBPhsNH2 composes a pocket that can access both tertiary and benzylic C-H bonds. The nonactivated tertiary C-H bond was selectively aminated in the presence of an electronically activated benzylic C-H bond. Both singlet and triplet energy surfaces were investigated in this study. The computational results suggest that the triplet stepwise pathway is more favorable than the singlet concerted pathway. In the hydrogen atom abstraction by Rh-nitrene species, which is the rate- and site-selectivity-determining step, there is an attractive π-π stacking interaction between the phenyl group of the substrate and the phthalimido group of the ligand in the tertiary C-H activation transition structure. By contrast, such attractive interaction is absent in the benzylic C-H amination transition structure. Therefore, the DFT computational results clearly demonstrate how the synergistic combination of the dirhodium complex with sulfamate overrides the intrinsic preference for benzylic C-H amination to achieve the amination of the nonactivated tertiary C-H bond.

A novel dressing seeded with embryonic artery CD133+ cells and loaded with the Sirt1 agonist SRT1720 accelerates the healing of diabetic ischemic ulcers.

Refractory ischemic ulcers that occur in patients with diabetes present a major clinical challenge. Embryonic artery cluster of differentiation 133+ cells (EACCs) may promote the healing of diabetic ulcers; however, the high glucose environment in the diabetic ulcers decreases the survival rate of transplanted EACCs and inhibit their biological function. Furthermore, microcirculation in diabetic ischemic ulcers is impaired, which inhibits the beneficial effect of EACCs. In the current study, the Sirt1 agonist SRT1720 was selected as a therapeutic drug and loaded into a dressing composed of PLGA, collagen and silk (PCSS) formed using electrospinning technology. EACCs were seeded onto the PCSS dressing and this was used to treat diabetic ulcers. The results indicated that SRT1720 promotes the proliferation of EACCs, enhances the secretion of vascular endothelial growth factor A, interluekin 8 and basic fibroblast growth factor, and inhibits the secretion of tumor necrosis factor α. Furthermore, SRT1720 promoted the paracrine function of EACCs and promoted the proliferation and migration of human umbilical vein endothelial cells. PCSS induced the steady release of SRT1720 over a 15-day period and PCSS seeded with EACCs (PCSS-EACCs) were transplanted into the diabetic ischemic ulcers of mice with diabetes. The results of these experiments indicated that angiogenesis and the healing of diabetic ischemic ulcers was significantly improved following the transplantation of PCSS-EACCs. Therefore, PCSS-EACCs may be a novel and effective treatment for diabetic ischemic ulcers.