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Isoflurane is one of the most popular inhalation anesthetics in the clinical practice but presenting an increased risk of neuronal injury. Hsp90 has been indicated to present an important role for maintaining neuronal homeostasis under the stress. However, the effect of hsp90 during isoflurane exposure is poorly understood. Here in this study, we aimed to observe the protect effect of hsp90 inhibition, and investigate the potential regulatory mechanism after isoflurane exposure. We found that hsp90 inhibitor, 17AAG, showed a great protective effect in maintaining isoflurane-induced ferroptosis of mice hippocampus and cultured neuronal cells. We focus on the crucial protein GPX4 activity in ferroptosis, and found that the 17 AAG contributed its protect effect to preserve physiological level of GPX4 activity under isoflurane exposure, although 17AAG could restored the protein level of GPX4. Further, we observed CMA pathway was activated and then mediated GPX4 degradation under isoflurane exposure. And 17AAG could interfere the complex between hsp90 and lamp2a to inhibit CMA activity, followed by blocking GPX4 degradation, which further affected the isoflurane-induced ferroptosis. Based on these findings, we proposed that hsp90 inhibition as a protective mechanism against isoflurane-induced ferroptosis in neurons.

Background HSP90 has been shown to play an important role in maintaining neuronal homeostasis under stressful conditions. However, the effect of HSP90 during isoflurane exposure is unknown. This study aimed to investigate the protective effect of HSP 90 inhibition following isoflurane exposure and elucidate the potential regulatory mechanisms in vivo and in vitro. Methods Isoflurane-induced hippocampal neuron injury model was established in aged male C57BL/6 mice. After pretreatment with HSP90 inhibitor 17 AAG, the mice were administrated to isoflurane inhalation. Human neuroblastoma SH-SY5Y cells were pretreated with 17AAG and exposed to isoflurane. The hippocampal neuronal injury in mice were examined by HE staining and immunofluorescent staining. Cell viability in SH-SY5Y cells was examined by CCK8 assay and trypan blue staining. Ferroptosis biomarkers were investigated by transmission electron microscopy, flow cytometry, and western blot. We also detected the CMA signaling pathway to test the effect of HSP90 in isoflurane-induced neurotoxicity. Results The HSP90 inhibitor, 17 AAG, reduced isoflurane-induced ferroptosis in the mouse hippocampus and cultured neuronal cells. Isoflurane activated the CMA pathway, which then mediated GPX4 degradation. 17 AAG contributed to the preservation of GPX4 activity at physiological levels under isoflurane exposure. In addition, 17 AAG inhibits CMA activity and GPX4 degradation by preventing the formation of complexes between HSP90 and LAMP2A, thereby affecting isoflurane-induced ferroptosis. Conclusions HSP90 inhibition protects against isoflurane-induced neurotoxicity in vivo and vitro via inhibition of CMA pathway and GPX4 degradation, which induced ferroptosis and thus neuronal cell death.

BACKGROUND: Parathyroidectomy under nerve monitoring has been carried out for nearly ten years in the China-Japan Union Hospital of Jilin University. We retrospectively evaluated patients’ prognosis with secondary hyperparathyroidism (SH) under neuro- and non-neuro-monitored parathyroidectomy anesthesia. The purpose of this study is to summarize and introduce a new anesthesia scheme for parathyroidectomy under nerve monitoring. METHODS: From January 2000 to December 2019, 200 patients with SH in the China-Japan Union Hospital of Jilin University were retrospectively analyzed. Among them, 100 patients underwent parathyroidectomy under neurological monitoring (Group A), and 100 patients underwent parathyroidectomy without neurological monitoring (Group B). The dosage of muscle relaxant, parathyroid hormone (PTH), serum calcium, phosphorus, urea, creatinine, and alkaline phosphatase (ALP) was recorded before surgery (T0), after surgery (T1), at discharge (T2), during skin incision (Ta), at four parathyroidectomies (Tb), and 10 min after total removal. The levels of PTH were measured at four-time points (Tc) and 30 minutes (Td) after complete resection. RESULTS: After screening and propensity score match (PSM), the data of 92 patients were analyzed. Group A’s muscle relaxant dose was significantly less than Group B; the length of hospital stay in Group A was significantly lower than in Group B (P

Background: To investigate whether closed-loop systems under bispectral index anesthesia depth monitoring can reduce the intraoperative propofol dosage. Methods: All randomized controlled trials (RCTs) on reducing propofol dosage under closed-loop systems were collected, and the literature was screened out, the abstracts and full texts were carefully read, and the references were tracked, data extraction and quality evaluation were conducted on the included research, and the RevMan5.3 software was used for meta-analysis. The main results were propofol and the incidence of adverse reactions such as hypertensive hypotension and postoperative cognitive dysfunction. A total of 879 cases were included in 8 articles, including 450 occurrences in the closed-loop system group and 429 cases in the open-loop system group. Results: Compared with manual control, closed-loop systems under bispectral index anesthesia depth monitoring reduced the dose of propofol (MD: −0.62, 95% CI: −1.08–−0.16, P = .008), with heterogeneity (I2 = 80%). Closed-loop systems significantly reduced the incidence of abnormal blood pressure (MD: −0.02, 95%CI: −0.05–0.01, P = .15, I2 = 74%) and postoperative cognitive dysfunction (MD: −0.08, 95% CI: −0.14 −0.01, P = .02, I2 = 94%). Conclusion: Bispectral index monitoring of propofol closed-loop target-controlled infusion system can reduce the amount of propofol, reduce the incidence of adverse reactions such as hypertensive or hypotension and postoperative cognitive dysfunction.

Circulatory stability of patients with cerebrovascular malformations during the surgery is critical to their prognosis. Anesthesia-induced intubation, tumor separation, clamping and other operations may cause severe fluctuations in blood pressure and even result in aneurysm rupture. As a highly efficient and selective adrenergic α2 receptor agonists, dexmedetomidine hydrochloride is able to regulate the release of catecholamine by means of negative feedback so as to control blood pressure. This study aims to assess the effects of dexmedetomidine hydrochloride on hemodynamics and cerebral oxygen metabolism of intraoperative patients with cerebrovascular malformations.

Objective: To compare effects of desflurane and sevoflurane on cognitive function in elderly patients undergoing general anesthesia. Methods Eighty elderly patients undergoing general anesthesia under open surgery were enrolled in this study, ASA I ~ II, were divided into group A (desflurane group) and group B (sevoflurane group) randomly. Intravenous drugs included midazolam 0.03 mg / kg, sufentanil 0.5ug / kg, propofol 1-2mg / kg, vecuronium 0.1 mg / kg. All patients were treated with desflurane or sevoflurane to maintain anesthesia, with depth 1.2 ~ 1.4MAC. The mini-mental state examination (MMSE) scores were recorded before operation and 1h, 6h, 12h, 24h and 48h after operation. Results The MMSE scores of the two groups had no significant difference before operation but were significantly lower than those before operation (P

The traditional thermal response factor method for load calculation employs invariable time-step. To ensure accuracy with the less possible computing quantity, the method with variable time steps i...

Objective: To investigate the efficacy of a single intravenous injection of oxycodone hydrochloride in patients undergoing laparoscopic rectal tumor resection with acute postoperative pain and evaluate the quality of Anesthesia recovery period. Methods: 60 patients for laparoscopic rectal tumor resection, were randomly divided into two groups (n=30 each): oxycodone hydrochloride injection group (group I) and fentanil injection group (group II). oxycodone 0.05mg / kg (saline dilution of 1mg / ml) or fentanil 0.1ug / kg was injected intravenously at the end of surgery. Assessing the OAA / S sedation grade and Prince-Henry postoperative pain scores. Results: Demographic data and anesthesia characteristics were similar in the two groups. Group II’s Prince-Henry pain score was significantly higher than the group I’s (P

The insecticidal IE648 toxin is a truncated Cry1Ie protein with increased toxicity against Asian corn borer (ACB). Cry toxins are pore-forming toxins that disrupt insect midgut cells to kill the larvae. However, the peritrophic membrane (PM) is an important barrier that Cry toxins must cross before binding to midgut cells. Previously, it was shown that Cry toxins are able to bind and accumulate in the PM of several lepidopteran insects. Binding of IE648 toxin to PM of ACB was previously reported and the goal of the current work was the identification of the binding region between Cry1Ie and the PM of ACB. Homologous competition binding assays showed that this interaction was specific. Heterologous competition binding assays performed with different fragments corresponding to domain I, domain II and domain III allowed us to identify that domain III participates in the interaction of IE648 with the PM. Specifically, peptide D3-L8 (corresponding to Cry1Ie toxin residues 607 to 616), located in an exposed loop region of domain III is probably involved in this interaction. Ligand blot assays show that IE648 interact with chitin and PM proteins with sizes of 30, 32 and 80 kDa. The fact that domain III interacts with proteins of similar molecular masses supports that this region of the toxin might be involved in PM interaction. These data provide for the first time the identification of domain III as a putative binding region between PM and 3D-Cry toxin.