Postoperative analgesic effect of parecoxib sodium local anesthesia in patients with breast cancer through systematic review and meta-analysis.

BACKGROUND: Postoperative pain can seriously affect a patient's recovery, and parecoxib sodium has a good analgesic effect. However, there is a lack of clinically systematic analyses of the effects of parecoxib sodium on postoperative pain in breast cancer patients. The aim of the present study was to systematically evaluate the efficacy and safety of parecoxib sodium local anesthesia in the treatment of postoperative pain in breast cancer patients. METHODS: Literature published from January 2010 to December 2020 was searched in the China National Knowledge Infrastructure database, Wanfang database, PubMed, and Cochrane Library. Literature on randomized controlled trials of parecoxib sodium local anesthesia in patients with breast cancer was collected. Method of treatment was extracted and literature quality was assessed. Meta-analyses of included literature were performed using RevMan 5.3. RESULTS: A total of 17 randomized controlled trials were included, with a total of 1,032 breast cancer surgery patients. The experimental group was treated with parecoxib sodium anesthesia, and the control group was treated with other anesthesia methods. The meta-analysis results showed that there were obvious differences among visual analogue scale (VAS) score of the experimental group and control group 2 h after surgery [mean difference (MD): -0.79; 95% confidence interval (CI): -1.29 to -0.29; P=0.002], 4 h (MD =-0.77; 95% CI: =-1.51 to -0.03; P=0.04), 6 h (MD: -1.10; 95% CI: -1.41 to -0.80; P<0.00001), 8 h (MD: -0.66; 95% CI: -1.00 to -0.33; P=0.0001), 12 h (MD: -0.92; 95% CI: -1.24 to -0.60; P<0.00001), 24 h (MD: -0.86; 95% CI: -1.15 to -0.58; P<0.00001), and 48 h (MD: -0.90; 95% CI: -1.47 to -0.33; P=0.002). Moreover, visual analog scale score and the postoperative controlled analgesia frequency of patients in the experimental group (MD: -2.08; 95% CI: -2.88 to -1.27; P<0.00001) and the incidence of adverse reactions (odds ratio: 0.52; 95% CI: 0.34-0.80; P=0.002) were significantly reduced. DISCUSSION: Parecoxib sodium local anesthesia for breast cancer patients has good postoperative analgesia and treatment safety.

mTOR signaling pathway is inhibited downstream of the cyclophilin D-mediated mitochondrial permeability transition in honokiol-triggered regulated necrosis.

Honokiol (HNK) is a pharmacologically active small molecule that is isolated from the traditional Chinese medicinal herb, houpu. It may induce diversified types of regulated cell death, which are dependent on different cell types and varying concentrations of therapeutic agent. We previously reported that HNK triggers a cyclophilin D (CypD)-mediated regulated necrosis in various cell lines at certain concentrations (two­fold higher than its half maximal inhibitory concentration). Subsequent study revealed that HNK induced cell death transition from early apoptosis to regulated necrosis in parallel with the increase of HNK dose. In the current study, a lower concentration of HNK (30 µg/ml) than previously reported also induced simplex CypD­mediated mitochondrial permeability transition (MPT)­associated regulated necrosis in the HEK­293 human embryonic kidney cell line. HNK, at concentration of 30 µg/ml, induced necrotic cell death in HEK­293 cells, which was demonstrated by positive staining for propidium iodide. No DNA ladder patterns or apoptotic bodies were detected in cells that underwent this type of necrotic cell death. Caspase­8 and ­3 were not activated during the process of HNK­induced necrosis. In addition, pan­caspase inhibitor, z­VAD­fmk and receptor­interacting protein 1 inhibitor, necrostatin­1 did not inhibit HNK­induced necrosis. However, CypD inhibitor, cyclosporin A (CsA), blocked HNK­induced necrosis. These findings indicate that 30 µg/ml HNK induced simplex CypD-mediated MPT­associated regulated necrosis in HEK­293 cells. Furthermore, the findings demonstrated that during HNK-triggered regulated necrosis the mammalian target of rapamycin (mTOR) signaling pathway is also inhibited. Pretreatment with CsA, therefore, inhibits HNK­triggered regulated necrosis and reverses dephosphorylation of Akt, eIF4E­binding protein 1 and S6 kinase. This indicated that the mTOR signaling pathway is effective downstream of the CypD­mediated MPT and before the onset of plasma membrane breakdown during the regulated necrosis process. Therefore, it has been demonstrated for the first time, to the best of our knowledge, that the mTOR signaling pathway was inhibited downstream of the CypD-mediated MPT in the process of HNK-induced regulated necrosis.