Efficacy and safety of remimazolam tosylate in hysteroscopy: A randomized, single-blind, parallel controlled trial.

WHAT IS KNOWN AND OBJECTIVE: To compare the effectiveness and safety of remimazolam tosylate and propofol for hysteroscopy. METHODS: From November 2020 to June 2021, a total of 90 patients who underwent hysteroscopy were prospectively enrolled in this study. The patients were randomly assigned to three groups: propofol group (group A), low-dose remimazolam tosylate group (group B), and high-dose remimazolam tosylate group (group C), with 30 cases in each group. All cases received intravenous sufentanil 0.1ug/kg for analgesic preconditioning. Patients in group A were given 2 mg/kg propofol intravenously, and maintained at a rate of 5 mg/kg/h. Patients in groups B and C were given intravenous remimazolam tosylate 0.25 mg/kg. Group B was maintained with remimazolam tosylate at a rate of 0.48 mg/kg/h, while group C was at a rate of 0.6 mg/kg/h. The changes of heart rate (HR), mean arterial pressure (MAP) and saturation of peripheral oxygen (SpO2) were recorded after admission (T0), 1 min after anaesthesia (T1), dilation of the uterine cavity (T2), and the end of hysteroscopy (T3). In addition, Observer's Assessment of Alertness/Sedation Scale (OAA/S) at 1 min, 3 min, and 5 min after hysteroscopy, the incidence of adverse events, and the time from the end of the hysteroscopy to reach the discharge standard, were recorded. RESULTS AND DISCUSSION: The success rate of sedation in each group was 100%. After administration, the adverse event incidence in group A was significantly higher than that in groups B and C (p < 0.05, respectively). Compared with propofol, remimazolam tosylate did not cause injection pain, had less impact on haemodynamics and caused less respiratory depression. WHAT IS NEW AND CONCLUSION: Remimazolam tosylate and propofol have similar success rates for painless hysteroscopy, and both can provide safe and effective sedation. The safety of remimazolam tosylate for hysteroscopy appears to be better than that of propofol.

FSC231 alleviates paclitaxel-induced neuralgia by inhibiting the interactions between PICK1 and GluA2 and activates GSK-3ß and ERK1/2.

BACKGROUND: FSC231, a PSD-95/DLG/ZO-1 (PDZ) domain inhibitor of protein kinase Cα interacting protein 1 (PICK1), has analgesic effects, but the mechanism remains unclear. METHODS: The expression level of PICK1 in dorsal root ganglion (DRG) of rats was changed by vector plasmid, and the effect of PICK1 on paclitaxel (PTL)-induced neuralgia of rats was observed in collaboration with FSC231 treatment. The possible molecular mechanisms were explored by quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot and co-immunoprecipitation (Co-IP) techniques. RESULTS: PTL treatment can significantly reduce mechanical withdrawal threshold (MWT), shorten thermal withdrawal latency (TWL), promote DRG inflammation and release of substance P (SP), stimulate PICK1 expression, decrease α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor 2 (AMPAR, GluA2) level and increase glycogen synthase kinase-3ß (GSK-3ß) and extracellular regulated protein kinases1/2 (ERK1/2) phosphorylation in rats, while FSC231 treatment can alleviate the above effects induced by PTL. Overexpression of PICK1 can counteract reduced PICK1 level, increased GluA2 level and decreased GSK-3ß and ERK1/2 phosphorylation levels caused by FSC231 treatment. The results of Co-IP confirmed the interactions between PICK1 and GluA2. Both FSC231 treatment and silent PICK1 improved PTL-induced MWT reduction, TWL shortening, inflammation, SP release and related gene expression changes, with cumulative effect. CONCLUSION: FSC231 activates GSK-3ß/ERK1/2 by inhibiting the interaction between PICK1 and GluA2 and alleviates PTL-induced DRG neuralgia in rats.