Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is transmissible through iatrogenic routes due to abundant infectious prions [misfolded forms of the prion protein (PrPSc)] in the central nervous system (CNS). Some epidemiological studies have associated sCJD risk with non-CNS surgeries. We explored the potential prion seeding activity and infectivity of skin from sCJD patients. Autopsy or biopsy skin samples from 38 patients [21 sCJD, 2 variant CJD (vCJD), and 15 non-CJD] were analyzed by Western blotting and real-time quaking-induced conversion (RT-QuIC) for PrPSc. Skin samples from two patients were further examined for prion infectivity by bioassay using two lines of humanized transgenic mice. Western blotting revealed dermal PrPSc in one of five deceased sCJD patients and one of two vCJD patients. However, the more sensitive RT-QuIC assay detected prion seeding activity in skin from all 23 CJD decedents but not in skin from any non-CJD control individuals (with other neurological conditions or other diseases) during blinded testing. Although sCJD patient skin contained ~103- to 105-fold lower prion seeding activity than did sCJD patient brain tissue, all 12 mice from two transgenic mouse lines inoculated with sCJD skin homogenates from two sCJD patients succumbed to prion disease within 564 days after inoculation. Our study demonstrates that the skin of sCJD patients contains both prion seeding activity and infectivity, which raises concerns about the potential for iatrogenic sCJD transmission via skin.

Prions are infectious proteins that cause a group of fatal transmissible diseases in animals and humans. The scrapie isoform (PrPSc) of the cellular prion protein (PrPC) is the only known component of the prion. Several lines of evidence have suggested that the formation and molecular features of PrPSc are associated with an abnormal unfolding/refolding process. Quiescin-sulfhydryl oxidase (QSOX) plays a role in protein folding by introducing disulfides into unfolded reduced proteins. Here we report that QSOX inhibits human prion propagation in protein misfolding cyclic amplification reactions and murine prion propagation in scrapie-infected neuroblastoma cells. Moreover, QSOX preferentially binds PrPSc from prion-infected human or animal brains, but not PrPC from uninfected brains. Surface plasmon resonance of the recombinant mouse PrP (moPrP) demonstrates that the affinity of QSOX for monomer is significantly lower than that for octamer (312 nM vs 1.7 nM). QSOX exhibits much lower affinity for N-terminally truncated moPrP (PrP89-230) than for the full-length moPrP (PrP23-231) (312 nM vs 2 nM), suggesting that the N-terminal region of PrP is critical for the interaction of PrP with QSOX. Our study indicates that QSOX may play a role in prion formation, which may open new therapeutic avenues for treating prion diseases.

Purpose. Partial cystectomy was investigated as a method of bladder preservation with better disease outcomes than transurethral bladder tumor resection in T1 high-grade bladder cancer patients. Method and materials. The national Surveillance, Epidemiology, and End Results database (SEER) (2004–2015) were used to obtain patients diagnosed with T1 high-grade bladder cancer, and finally, 25263 patients were enrolled in our study. The Kaplan–Meier method with the log-rank test was performed to analyze the outcome of overall survival (OS) and cancer-specific survival (CSS) between patients undergoing partial cystectomy (PC), transurethral resection of bladder tumor (TURBT), or radical cystectomy (RC). Moreover, the propensity score matching (PSM) and multivariable Cox proportional hazard model were also utilized in the study. Results. Ultimately, 24635 patients were undergoing TURBT, while 190 and 438 patients were, respectively, assigned to the PC and RC groups. Compared with patients with TURBT, a tendency of a higher proportion of higher older and male patients was observed in the PC group. When matching with RC patients, patients in the PC group were commonly older and had bigger tumor sizes and single tumors (All P < 0.05 ). After 1 : 1 PSM, 190 patients with TURBT and 160 patients receiving PC were selected. In survival analysis, the patients in the PC group had a higher survival probability of both OS and CSS before and after PSM compared with those in the TURBT group. Meanwhile, no significant differences were observed between the RC and PC groups in OS and CSS analysis. Moreover, multivariable Cox regression showed that PC was a protective factor for overall mortality (ACM) and cancer-specific mortality (CSM) compared with TURBT in T1 high-grade patients (All P < 0.05 ). Conclusion. Patients undergoing partial cystectomy were shown to have a better outcome compared with those with transurethral bladder tumor resection in T1 high-grade bladder cancer patients. Partial cystectomy could be the more worthwhile choice for bladder preservation in T1 high-grade bladder cancer patients.