USP5 facilitates bladder cancer progression by stabilizing the c-Jun protein.

BACKGROUND: Bladder cancer is the second most common genitourinary malignancy worldwide. The death rate of bladder cancer has increased every year. However, the molecular mechanism of bladder cancer is not sufficiently studied. Deubiquitinating enzymes (DUBs) play an important role in carcinogenesis. Several studies have demonstrated that USP5 associated with malignancy and pathological progression in hepatocellular carcinoma, colorectal and non-small cell lung cancer. However, the role of USP5 in bladder cancer need to be explored. METHODS: The USP5 expression was analysed using the web server GEPIA. To explore USP5 function in bladder cancer, we constructed USP5-knockout cell lines in T24 cells. A FLAG-USP5 (WT USP5) plasmid and a plasmid FLAG-USP5 C335A (catalytic-inactive mutant) used to overexpress USP5 in EJ cells. CCK8, colony formation, transwell and scratch assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP5 and c-Jun. Cycloheximide (CHX) chase assays were performed to establish the effect of USP5 on c-Jun stability. Xenograft mouse model was used to study the role of USP5 in bladder cancer. RESULTS: USP5 expression is increased in bladder cancer patients. Genetic ablation of USP5 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. RNA-seq and luciferase pathway screening showed that USP5 activated JNK signalling, and we identified the interaction between USP5 and c-Jun. USP5 was found to activate c-Jun by inhibiting its ubiquitination. CONCLUSIONS: Our results show that high USP5 expression promotes bladder cancer progression by stabilizing c-Jun and that USP5 is a potential therapeutic target in bladder cancer.

Incidence of postoperative sore throat after using a new technique of insertion of a second generation Laryngeal Mask Airway: A randomised controlled trial.

BACKGROUND: Sore throat is a common complication after Laryngeal Mask Airway Supreme (SLMA) insertion. OBJECTIVE: The aim of this study was to determine whether a new SLMA insertion technique (not removing the pilot tube blocker before insertion) lowers the incidence of sore throat in the postanaesthesia care unit (PACU). DESIGN: A prospective, single-centre, parallel randomised controlled trial. SETTING: Operating room and PACU at a hospital in China from June to September 2019. PATIENTS: Four hundred and eight patients aged 18 to 65 years with American Society of Anaesthesiologists physical status class I or II who were scheduled for elective surgery requiring anaesthesia and SLMA insertion. INTERVENTIONS: Leaving the blocker at the end of the pilot tube in situ (this blocker keeps the valve open and the balloon remains partially inflated but will deflate with pressure) or removing the blocker and actively deflating the cuff before SLMA insertion. MAIN OUTCOME MEASURES: The primary outcome was the incidence of postoperative sore throat in the PACU. The secondary outcomes included sore throat severity (Prince Henry Hospital Pain Score), first-attempt success rate, ease of insertion, time to successful SLMA insertion, oropharyngeal leak pressure, grade of view on fibreoptic bronchoscopy (indicating the accuracy of SLMA positioning) and adverse events. RESULTS: The incidence of sore throat was 33/204 (16.2%) in the nonremoval group, and 65/204 (31.9%) in the removal group (P < 0.001). The first-attempt success rate was 174/204 (85.3%) in the nonremoval group and 150/204 (73.76%) in the removal group (P = 0.003; relative risk 1.160, 95% CI 1.049 to 1.282). The Kaplan--Meier curves showed that the insertion time in the nonremoval group was shorter (log-rank P = 0.01). CONCLUSION: The new insertion technique, leaving the blocker attached to the end of the pilot balloon, resulted in a reduced incidence and severity of postoperative sore throat in the PACU, and an improved first-attempt success rate and the accuracy of SLMA positioning. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR1900023022.

Application of Intravenous Lidocaine in Obese Patients Undergoing Painless Colonoscopy: A Prospective, Randomized, Double-Blind, Controlled Study.

OBJECTIVE: Propofol for procedural sedation and analgesia (PSA) for colonoscopy can result in a high prevalence of severe respiratory depression. Studies have shown that intravenous (IV) infusion of lidocaine can reduce propofol requirements significantly and increase the ventilatory response to carbon dioxide in humans. We tested the hypothesis that IV lidocaine could improve propofol-induced respiratory depression in obese patients during colonoscopy. METHODS: Ninety obese patients scheduled for painless colonoscopy were randomized to receive lidocaine (1.5 mg/kg, then 2 mg/kg/h, IV) or the same volume of 0.9% saline. Intraoperative sedation was provided by propofol. The primary outcome was the number of oxygen-desaturation episodes. Secondary outcomes were: the number of apnea episodes; total propofol consumption; time to the first hypoxia episode; time to consciousness loss; intraoperative hemodynamic parameters; awakening time; adverse events; duration of post-anesthesia care unit (PACU) stay; satisfaction of endoscopists and patients. RESULTS: Demographic characteristics between the two groups were comparable. The number of oxygen-desaturation episodes in group L (1.49±1.12) decreased by 0.622 (P=0.018) compared with that in group N (2.11±1.32), and the number of apnea episodes in group L decreased by 0.533 (P<0.001). Kaplan-Meier curves showed that the median time to the first hypoxia episode was longer in group L (86.78 s) than that in group N (63.83 s) (Log rank P=0.0008). The total propofol consumption, awakening time, and duration of PACU stay were reduced in group L. There was no significant difference in the prevalence of adverse events (P>0.05 for all). Satisfaction scores for endoscopists and patients in group L were higher than that in group N (P<0.001). CONCLUSION: Intravenous infusion of lidocaine could significantly reduce the number of oxygen-desaturation and apnea episodes in obese patients during painless colonoscopy. This method is worthy of clinical promotion. CLINICAL TRIALS REGISTRATION: ChiCTR2000028937.