Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic-assisted total gastrectomy: a randomized controlled trial.

BACKGROUND: Low immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. METHODS: Fifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h- 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue. RESULTS: Compared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group. CONCLUSION: Laparoscopic total gastrectomy patients can benefit from 0.05 ug/kg- 1. h- 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).

Comparison Effects of Propofol-Dexmedetomidine versus Propofol-Remifentanil for Endoscopic Ultrasonography: A Prospective Randomized Comparative Trial.

Objective: To compare the effects of propofol-dexmedetomidine versus propofol-remifentanil for endoscopic ultrasonography (EUS). Design, Setting, and Participants. A single-center, randomized trial from August 20, 2020 to August 20, 2021, in patients undergoing EUS. Interventions. Propofol-dexmedetomidine (PD) versus propofol-remifentanil (PR). Outcome Measures. The primary outcome was the endoscopist satisfaction level. The secondary outcomes included patient satisfaction, the incidence of adverse events, induction time, and time to achieve postanesthesia discharge score (PADS) ≥9. Methods: Total of 200 patients were enrolled and randomized into PD and PR groups. A bolus dose of 0.5 µg/kg dexmedetomidine was injected intravenously for 5 min. Subsequently, a continuous infusion of 0.5 µg/kg/h for the PD group. Remifentanil was continuously infused at 1.5 µg/kg/h for the PR group. A bolus dose of 1 mg/kg propofol was administered to both groups and then continuously infused. Results: The endoscopist satisfaction level was higher in the PR group than in the PD group (P = 0.009). Patient satisfaction was not significantly different between the groups (P = 0.738). No patients required mask ventilation or tracheal intubation in both groups. All patients were relatively hemodynamically stable. The incidence of body movements during the procedure in the PD group was higher than in the PR group (P = 0.035). The induction time and time taken to achieve PADS ≥9 in the PD group were longer than in the PR group (P < 0.05). Conclusions: PR sedation can increase the satisfaction level of the endoscopist by providing faster induction time and lower body movement and that of the patient by achieving faster PADS than PD sedation. Trial registration number: http://www.chictr.org.cn (ChiCTR2000034987).

Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer.

Previous studies have shown that some anesthesia drugs can inhibit tumor growth and metastasis. As a clinical anesthetic drug, dezocine has been reported to play an important role in immune function. However, the effects of dezocine on ovarian cancer cell growth and metastasis are not fully understood. In this study, we found that dezocine dose-dependently inhibited the viability of ES-2 and SKOV3 cells. Dezocine suppressed the migration and invasion abilities of ovarian cancer cells, and promoted apoptosis. Moreover, the Akt/mTOR signaling pathway was also inhibited by dezocine. Furthermore, mechanism study showed that dezocine could significantly inhibit the expression of CRABP2, and CRABP2 overexpression reversed the inhibitory effects of dezocine on ovarian cancer cell proliferation and migration. In conclusion, dezocine has significant anti-tumor effects on the growth and metastatic potential of ovarian cancer cells, and CRABP2 functions as a downstream effector of dezocine.

Genistein Attenuates Isoflurane-Induced Neuroinflammation by Inhibiting TLR4-Mediated Microglial-Polarization in vivo and in vitro.

BACKGROUND: Isoflurane, a widely used anesthetic in surgery, has been found to induce neurotoxicity. In parallel, genistein is thought to attenuate isoflurane-induced neurotoxicity, although underlying molecular mechanisms are still unclear. In this study, we studied the protective effects of genistein on isoflurane-induced neuroinflammation in rats and BV2 cells. METHODS: Sprague-Dawley rat pups were exposed to 0.75% isoflurane for 6 hours at postnatal day 7 (P7), and genistein (20, 40, or 80 mg/kg/day) or saline administered from P3 to P15. Hippocampal single-cell suspensions were prepared and apoptosis analyzed by flow cytometry. mRNA expression was determined by RT-qPCR, while protein expression was assessed using Western blot, immunochemistry and immunofluorescence. TLR4 was knocked-out in BV2 cells through CRISPR-Cas9. RESULTS: Genistein treatment reduced isoflurane-induced apoptosis and inflammation in rat hippocampus. Importantly, genistein promoted M2 and suppressed M1 microglia polarization in rat hippocampus after stimulation with isoflurane. In addition, genistein reduced isoflurane-induced protein expression levels of TLR4, MyD88, TRAF6, p-TAK1, p-p38, p-ERK, p-IκBα and p-NF-κB in rat hippocampus. In BV2 cells exposed to isoflurane, genistein treatment decreased IL-1ß, TNF-α, IL-6 and IL-8 mRNA expressions, promoted M2 and suppressed M1 microglia polarization. Similarly, genistein also decreased TLR4 protein levels in isoflurane-induced BV2 cells. However, genistein did not affect CD16, iNOS, CD206 and Arg1 protein levels in TLR4-KO BV2 cells exposed to isoflurane. CONCLUSION: Genistein attenuates isoflurane-induced neurotoxicity by inhibiting TLR4-mediated microglial inflammation in vivo and in vitro.