Thoracic paravertebral block for perioperative lung preservation during VATS pulmonary surgery: study protocol of a randomized clinical trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) extend the length of stay of patients and increase the perioperative mortality rate after video-assisted thoracoscopic (VATS) pulmonary surgery. Thoracic paravertebral block (TPVB) provides effective analgesia after VATS surgery; however, little is known about the effect of TPVB on the incidence of PPCs. The aim of this study is to determine whether TPVB combined with GA causes fewer PPCs and provides better perioperative lung protection in patients undergoing VATS pulmonary surgery than simple general anaesthesia. METHODS: A total of 302 patients undergoing VATS pulmonary surgery will be randomly divided into two groups: the paravertebral block group (PV group) and the control group (C group). Patients in the PV group will receive TPVB: 15 ml of 0.5% ropivacaine will be administered to the T4 and T7 thoracic paravertebral spaces before general anaesthesia induction. Patients in the C group will not undergo the intervention. Both groups of patients will be subjected to a protective ventilation strategy during the operation. Perioperative protective mechanical ventilation and standard fluid management will be applied in both groups. Patient-controlled intravenous analgesia is used for postoperative analgesia. The primary endpoint is a composite outcome of PPCs within 7 days after surgery. Secondary endpoints include blood gas analysis, postoperative lung ultrasound score, NRS score, QoR-15 score, hospitalization-related indicators and long-term prognosis indicators. DISCUSSION: This study will better evaluate the impact of TPVB on the incidence of PPCs and the long-term prognosis in patients undergoing VATS lobectomy/segmentectomy. The results may provide clinical evidence for optimizing perioperative lung protection strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT05922449 . Registered on June 25, 2023.

High glucose and bupivacaine­induced cytotoxicity is mediated by enhanced apoptosis and impaired autophagy via the PERK­ATF4­CHOP and IRE1­TRAF2 signaling pathways.

Bupivacaine has previously been reported to induce neurotoxicity, which is further enhanced by high glucose levels. In the present study, the underlying molecular mechanisms via which bupivacaine induces cytotoxicity under high glucose conditions were investigated in cultured human SH­SY5Y cells. In order to identify the optimal concentrations of glucose and bupivacaine that induced cytotoxicity, SH­SY5Y cells were treated with 30­100 mM glucose and 0.5­1.0 mM bupivacaine. Based on the dose response experiments, 50 mM glucose and 0.5 mM bupivacaine was used in the present study. The effects that 3­MA (autophagy inhibitor) and rapamycin (RAPA; autophagy inducer) exerted on cell apoptosis, autophagy and the expression of protein kinase R­like endoplasmic reticulum kinase (PERK)­activating transcription factor 4 (ATF4)­C/EBP­homologous protein (CHOP) and inositol­requiring enzyme 1 (IRE1)­tumor necrosis factor receptor associated factor 2 (TRAF2) signaling proteins were measured in high glucose and bupivacaine­treated cells. Cell viability was measured using a Cell Counting Kit­8 assay, cell apoptosis was assessed using flow cytometry, and protein expression was determined using western blot analyses. Compared with the control group, high glucose and bupivacaine significantly increased ATF4, CHOP and caspase­12 expression, increased apoptosis, and decreased p­IRE1, TRAF2, LC3­II/LC3­I and Beclin1 expression. Promoting autophagy with RAPA partly reversed the high glucose and bupivacaine­induced changes in p­PERK, CHOP, TRAF2, Beclin1, caspase­12 and apoptosis, while inhibiting autophagy with 3­MA further enhanced the changes in ATF4, CHOP, p­IRE1, TRAF2 and apoptosis. High glucose and bupivacaine induced cytotoxicity in SH­SY5Y cells, at least in part, through enhancing cell apoptosis and inhibiting autophagy via the PERK­ATF4­CHOP and IRE1­TRAF2 signaling pathways.

MicroRNA Profiling of Exosomes Derived from Red Blood Cell Units: Implications in Transfusion-Related Immunomodulation.

PURPOSE: To elucidate the microRNAs existent in exosomes derived from stored red blood cell (RBC) unit and their potential function. MATERIALS AND METHODS: Exosomes were isolated from the supernatant derived from stored RBC units by sequential centrifugation. Isolated exosomes were characterized by TEM (transmission electron microscopy), western blotting, and DLS (dynamic light scattering). MicroRNA (miRNA) microarray was performed to detect the expression of miRNAs in 3 exosome samples. Results revealed miRNAs that were simultaneously expressed in the 3 exosome samples and were previously reported to exist in mature RBCs. Functions and potential pathways of some detected miRNAs were illustrated by bioinformatic analysis. Validation of the top 3 abundant miRNAs was carried out by qRT-PCR (quantitative reverse transcription-polymerase chain reaction). RESULTS: TEM and DLS revealed the mean size of the exosomes (RBC-derived) as 64.08 nm. These exosomes exhibited higher abundance of short RNA than the long RNA. 78 miRNAs were simultaneously detected in 3 exosome samples and mature RBCs. Several biological processes might be impacted by these miRNAs, through their target gene(s) enriched in a particular signalling pathway. The top 3 (abundant) miRNAs detected were as follows: miR-125b-5p, miR-4454, and miR-451a. qRT-PCR revealed higher abundance of miR-451a than others. Only miR-4454 and miR-451a abundance tended to increase with increasing storage time. CONCLUSION: Exosomes derived from stored RBC units possessed multiple miRNAs and, hence, could serve various functions. The function of exosomes (RBC-derived) might be implemented partly by the predominantly enriched miR-451a.