Objective. This study explores the effect and mechanism of propofol for thyroid tumor. Methods. Culture human normal thyroid cells Nthy-ori 3-1 and thyroid cancer cell line TPC-1. TPC-1 cells were divided into the propofol group (treated with propofol), miR-141-3p group (transfected with the miR-141-3p mimic), negative control group (transfected with miR-NC), miR-141-3p + pcDNA-BRD4 group (transfected with the miR-141-3p mimic and pcDNA-BRD4), miR-141-3p + pcDNA group (transfected with the miR-141-3p mimic and pcDNA), siBRD4 group (transfected with siBRD4), and si-control group (transfected with si-control). The detection of miR-141-3p and BRD4 expression in cells was done by RT-qPCR, and the dual-luciferase reporter gene method and western blotting were used to verify the targeting relationship between miR-141-3p and BRD4. MTT method was used to test cell proliferation, transwell method was used to test cell migration and invasion, and western blotting was used to test SHH, GLI1, p-PI3K, and p-AKT protein expression. Results. Compared with Nthy-ori 3-1 cells, the expression of miR-141-3p in TPC-1 cells was markedly decreased. Propofol treatment and excessive expression of miR-141-3p could influence the phenotype of TPC-1 cells. BRD4 is one of the target genes of miR-141-3p, and its expression is negatively regulated by miR-141-3p. Overexpression of BRD4 can partially reverse the restraining effect of miR-141-3p on the TPC-1 cell phenotype. Both miR-141-3p and BRD4 can regulate the activity of SHH and PI3K/AKT signaling pathways. Conclusion. Propofol can inhibit the activity of SHH and PI3K/AKT pathways by targeting downregulating BRD4 through miR-141-3p, thereby inhibiting the phenotype of TPC-1 cells.

Background Cervical conization is a brief but painful procedure that can be performed under deep sedation with propofol and opioids. However, this sedation approach comes with a high risk of sedation-related adverse events (SRAEs). Esketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has the property of less cardiorespiratory depression than opioids. The aim of this study was to assess the efficacy and safety of adding a low-dose esketamine to propofol and sufentanil sedation as an opioid-reduced regimen. Methods 122 consecutive patients with ASA Ⅰ-Ⅲ, body mass index < 30, STOP-BANG score < 3 who underwent cervical conization were enrolled and randomly divided into group S and group ES. Using a closed-loop target-controlled infusion (TCI) pump with target bispectral index (BIS) value of 60 ± 5, patients in group S were sedated with 0.2µg/kg sufentanil and propofol, while patients in group ES were sedated with 0.15mg/kg esketamine, 0.1µg/kg sufentanil and propofol. The primary endpoint was the composite incidence of SRAEs, while the second endpoints included effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, and patient and gynecologist satisfaction. Results Data of 120 patients were analyzed. The incidence of composite SRAEs was significantly higher in group S compared to group ES (85.0% vs 56.7%, P < 0.05). Furthermore, the severity of SRAEs was higher in group S compared to group ES (P < 0.001). There were no significant differences in the success of sedation, awakening time, psychotomimetic side effects, postoperative nausea and vomiting, postoperative pain, and patient and gynecologist satisfaction between the two groups. Conclusion Adding a low-dose esketamine to propofol and sufentanil sedation reduces the incidence and severity of SRAEs in patients undergoing cervical conization, with equal sedation efficacy, recovery quality, and no additional psychomimetic side effects. Trial registration ChiCTR2000040457, 28/11/2020

women of the Asian region. Irinotecan is used as a first-and second-line regimen for metastatic colorectal, small cell lung and some other cancer types. The objective of this study was to develop Irinotecan nanoparticles (NPs) using folate-chitosan conjugate (FCC) for more effective delivery of Irinotecan on breast cancer cells. Methods: In this study, we synthesized the FCC system using carbodiimide synthesis. Irinotecan loaded FCC NPs were synthesized by ionic cross-linking with sodium tripolyphosphate. The effect of several variables on the NPs' characteristics was assessed, including the amount of drug and FCC ratio. The entrapment efficiency and the particle size distribution of irinotecan were optimized by changing these variables. The cytotoxicity of the particles was evaluated by cell viability assay (MTT assay) using breast cancer cell line (MCF-7). Results: NPs were spherical with a comparatively mono-dispersed size distribution (average size 93 nm) and negative zeta potential. Selected optimized formulation (F9) showed a suitable size distribution (105 nm) with relatively high drug entrapment (>75%). MTT assay showed a stronger cytotoxicity of F9 against MCF-7 cancer cells than control NPs and irinotecan free drug. Since breast cancer cells express folate receptors on their surface, these irinotecan loaded folic acid-Chitosan conjugated NPs could be used for targeted delivery against metastatic breast cancer with some modifications. Conclusions: Our study findings demonstrated that the designed NPs show suitable characteristic and also great potential for further in vivo cancer evaluation.Legal entity responsible for the study: N/A Funding: None Disclosure: All authors have declared no conflicts of interest.