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This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (

Introduction Elderly patients are at a high risk of postoperative delirium (POD), leading to increased postoperative morbidity and mortality. The use of dexmedetomidine and depth of anaesthesia may influence POD. This study aims to determine the effects of dexmedetomidine infusion versus normal saline placebo during light versus deep anaesthesia on POD among elderly patients undergoing major non-cardiac surgery.Methods and analysis This prospective, multicentre, randomised, controlled, factorial trial will be conducted at three tertiary hospitals in Jiangsu, China. We will recruit a total of 420 patients who are at least 60 years old and undergoing major non-cardiac surgery (thoracic, abdominal, urology, orthopaedic and spine surgery) under general anaesthesia. Patients will be randomised (1:1:1:1) to receive one of four anaesthesia regimens: (1) dexmedetomidine and light anaesthesia, (2) dexmedetomidine and deep anaesthesia, (3) placebo and light anaesthesia or (4) placebo and deep anaesthesia. Dexmedetomidine will be infused at 0.5 µg/kg/h throughout surgery, and intraoperative bispectral index target will be 55 for light anaesthesia and 40 for deep anaesthesia. The primary outcome is the occurrence of POD during the first 7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method two times per day. The secondary outcomes include days with POD, type of POD, pain scores at rest and on movement at 24 and 48 hours postoperatively, patient-controlled intravenous fentanyl consumption during 0–24 and 24–48 hours postoperatively, hypotension, bradycardia, postoperative nausea and vomiting, non-delirium complications, length of postoperative hospital stay, 30-day cognitive function and 30-day mortality. Data will be analysed on a modified intention-to-treat basis.Ethics and dissemination This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and each participating centre. The trial results will be published in a peer-reviewed journal.Trial registration Chinese Clinical Trial Registry (ChiCTR2300073271)

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery. Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0–24 h and 24–48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay. Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery. Trial registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766).

Abstract Background Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed to assess the role of microglia and complement C1q in sevoflurane-induced neurotoxicity and explore the underlying mechanisms. Methods Neonatal mice were treated with sevoflurane on postnatal days 6, 8, and 10, and the Morris water maze was performed to assess cognitive functions. For mechanistic explorations, mice were treated with minocycline, C1q-antibody ANX005, and sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before sevoflurane exposures. Western blotting, RT-qPCR, Golgi staining, 3D reconstruction and engulfment analysis, immunofluorescence, and microglial morphology analysis were performed. In vitro experiments were conducted in microglial cell line BV2 cells. Results Repeated neonatal sevoflurane exposures resulted in deficiencies in learning and cognition of young mice, accompanied by microglial activation and synapse loss. Sevoflurane enhanced microglia-mediated synapse elimination through C1q binding to synapses. Inhibition of microglial activation and phagocytosis with minocycline significantly reduced the loss of synapses. We further revealed the involvement of neuronal sialic acids in this process. The enhanced activity of sialidase by sevoflurane led to the loss of sialic acids, which facilitated C1q binding to synapses. Inhibition of C1q with ANX005 or inhibition of sialidase with NADNA significantly rescued microglia-mediated synapse loss and improved neurocognitive function. Sevoflurane enhanced the engulfment of BV2 cells, which was reversed by ANX005. Conclusions Our findings demonstrated that C1q-mediated microglial synaptic elimination by enhancing desialylation contributed to sevoflurane-induced developmental neurotoxicity. Inhibition of C1q or sialidase may be a potential therapeutic strategy for this neurotoxicity.

Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery. Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 μg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0–7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0–7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis. Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery. Ethics and dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300073163).

Background: Labor epidural analgesia (LEA) may influence gut microbiota. We explored the association between LEA and gut microbiota for both mothers and their newborns. Methods: In this prospective cohort study, parturients aged 25–35 years with a gestational age of 37–42 weeks and planned vaginal delivery were recruited. Twenty-one parturients received LEA (the LEA group), and 24 did not (the control group). Maternal and neonatal fecal samples were collected, and the gut microbiota profiles were analyzed using the 16S rRNA gene sequencing. The impact of LEA on gut microbiota was assessed using the general liner models. Results: We showcased the gut microbiota profile from the phyla to species levels based on data on 45 mother-newborn dyads. The results of α- and β-diversity suggested significant changes in gut microbiota between the LEA and control groups. After adjusting for baseline confounders, the administration of LEA had positive correlations with R. ilealis (β = 91.87, adjusted P = 0.007) in mothers; LEA also had negative correlations with A. pittii (β = −449.36, adjusted P = 0.015), P. aeruginosa (β = −192.55, adjusted P = 0.008), or S. maltophilia (β = −142.62, adjusted P = 0.001) in mothers, and with Muribaculaceae (β = −2702.77, adjusted P = 0.003) in neonates. Conclusion: LEA was associated with changes in maternal and neonatal gut microbiota, and future studies are still required to assess their impact on clinical outcomes and explore the mechanisms.

Abstract Background Postoperative nausea and vomiting (PONV) are common after general anesthesia and surgery. This study aims to compare the effects of total intravenous opioid-free anesthesia (OFA) with conventional opioid-based anesthesia (OBA) on PONV in patients following treatments for wounds of lower extremities. Methods This randomized, double-blind, crossover trial will include a total of 72 adult patients scheduled for at least two separate surgical treatments of lower extremity wounds under general anesthesia. Patients will be randomized to 1 of 2 anesthesia sequences of OFA and OBA. Patients in sequence 1 will receive OFA in the first treatment procedure and OBA in the second procedure, while patients in sequence 2 will receive the two anesthesia regimens in the reverse order. The washout period is at least 5 days. OFA will be delivered with intravenous esketamine, lidocaine, dexmedetomidine, and propofol. OBA will be delivered with intravenous sufentanil and propofol. The primary endpoint is the incidence of PONV within the first 48 h postoperatively. The secondary endpoints are the severity of PONV, antiemetic rescue therapy, postoperative pain scores, the worst pain, need for rescue analgesia, postoperative sedation, hypotension, bradycardia, hypertension, tachycardia, hypoxemia, psychotomimetic or dissociative effects, time to extubation, and length of postanesthesia care unit stay. Patients who complete two surgical procedures with designated anesthesia regimens will be included in the final analyses. Discussion This crossover trial will determine whether total intravenous OFA reduces PONV in patients following treatments for lower extremity wounds. The results of this trial will also represent an important step to understand the benefits and possible risks of OFA in surgical patients. Trial registration Chinese Clinical Trial Registry (ChiCTR2200061511).

Background: Postoperative delirium (POD) is a common complication following cardiac surgery and increases postoperative morbidity and mortality. Intraoperative electroencephalogram (EEG) burst suppression suggests excessively deep anesthesia and predicts POD. Use of remimazolam provides a stable hemodynamic status and an appropriate depth of anesthesia. We aim to assess remimazolam administered for anesthesia and sedation in elderly patients having cardiac surgery. Methods: This is a randomized controlled clinical trial with noninferiority design. A total of 260 elderly patients aged equal to or greater than 60 years undergoing cardiac surgery will be randomly allocated to receive remimazolam or propofol (1:1) for general anesthesia and postoperative sedation until extubation. The primary outcome is the cumulative time with EEG burst suppression which is obtained from the SedLine system. The noninferiority margin is 2.0 min. The secondary outcomes include the POD occurrence within the first 5 days postoperatively and the duration of perioperative hypotension. Discussion: This noninferiority trial is the first to evaluate the effect of perioperative remimazolam administration on EEG burst suppression, POD occurrence, and duration of hypotension in elderly patients who undergo cardiac surgery. Trial registration: Chinese Clinical Trial Registry (ChiCTR2200056353).

Introduction: Bacterial pneumonia poses a significant global public health challenge, where unaddressed pathogens and inflammation can exacerbate acute lung injury and prompt cytokine storms, increasing mortality rates. Alveolar macrophages are pivotal in preserving lung equilibrium. Excessive inflammation can trigger necrosis in these cells, disrupting the delicate interplay between inflammation and tissue repair.Methods: We obtained extracellular vesicle from aloe and tested the biosafety by cell viability and hemolysis assays. Confocal microscopy and flow cytometry were used to detect the uptake and internalization of extracellular vesicle by macrophages and the ability of extracellular vesicle to affect the phenotypic reprogramming of macrophages in vitro. Finally, we conducted a clinical feasibility study employing clinical bronchoalveolar lavage fluid as a representative model to assess the effective repolarization of macrophages influenced by extracellular vesicle.Results: In our study, we discovered the potential of extracellular vesicle nanovesicles derived from aloe in reprograming macrophage phenotypes. Pro-inflammatory macrophages undergo a transition toward an anti-inflammatory immune phenotype through phagocytosing and internalizing these aloe vera-derived extracellular vesicle nanovesicles. This transition results in the release of anti-inflammatory IL-10, effectively curbing inflammation and fostering lung tissue repair.Discussion: These findings firmly establish the immunomodulatory impact of aloe-derived extracellular vesicle nanovesicles on macrophages, proposing their potential as a therapeutic strategy to modulate macrophage immunity in bacterial pneumonia.

Abstract Background Adequate sedation is essential for pediatric patients undergoing 3Tesla (T) magnetic resonance imaging (MRI). Using propofol alone is associated with patient arousing and adverse airway events. This study aimed to assess esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3 T MRI. Methods In this randomized, double-blind, controlled trial, 114 pediatric patients aged between 6 months and 8 years were randomly assigned, in a 1:1 ratio, to the esketamine–propofol group or the dexmedetomidine–propofol group. Sedation was provided with esketamine or dexmedetomidine in combination with propofol titration. The primary outcome was the total dose of propofol. Secondary outcomes included propofol infusion dose, adverse events, time to emergence from sedation, and time to discharge from recovery room. Results A total of 111 patients completed this study (56 in the esketamine–propofol group and 55 in the dexmedetomidine–propofol group). All MRI procedures were successfully performed under sedation. The total median (IQR) dose of propofol was significantly lower in the esketamine–propofol group (159.8 [121.7, 245.2] μg/kg/min) than that in the dexmedetomidine–propofol group (219.3 [188.6, 314.8] μg/kg/min) (difference in medians [95% CI] = − 66.9 [− 87.8 to − 43.0] μg/kg/min, P

Introduction Post-induction hypotension (PIH) is a common event in elderly surgical patients and is associated with increased postoperative morbidity and mortality. This study aims to develop and validate a PIH prediction model for elderly patients undergoing elective non-cardiac surgery to identify potential PIH in advance and help to take preventive measures.Methods and analysis A total of 938 elderly surgical patients (n=657 for development and internal validation, n=281 for temporal validation) will be continuously recruited at The First Affiliated Hospital of Soochow University in Suzhou, China. The main outcome is PIH during the first 15 min after anaesthesia induction or before skin incision (whichever occurs first). We select candidate predictors based on published literature, professional knowledge and clinical expertise. For model development, we will use the least absolute shrinkage and selection operator regression analysis and multivariable logistic regression. For internal validation, we will apply the bootstrapping technique. After model development and internal validation, temporal validation will be conducted in patients recruited in another time period. We will use the discrimination, calibration and max-rescaled Brier score in the temporal validation cohort. Furthermore, the clinical utility of the prediction model will be assessed using the decision curve analysis, and the results will be presented in a nomogram and a web-based risk calculator.Ethics and dissemination Ethical approval was obtained from the Ethics Committee of the First Affiliated Hospital of Soochow University (Approval No. 2023-012). This PIH risk prediction model will be published in a peer-reviewed journal.Trial registration number ChiCTR2200066201.

BackgroundDepressive symptoms are common among patients with lung cancer. We aimed to assess the effects of esketamine on postoperative depressive symptoms after thoracoscopic lung cancer surgery.MethodsIn this randomized, double-blind, placebo-controlled trial, 156 patients undergoing thoracoscopic lung cancer surgery were randomly allocated in a 1:1 ratio to receive intravenous esketamine (intraoperatively and in patient-controlled analgesia until 48 h postoperatively) or normal saline placebo. The primary outcome was the proportion of patients with depressive symptoms at 1 month postoperatively, assessed using the Beck Depression Inventory-II (BDI-II). Secondary outcomes included depressive symptoms at 48 h postoperatively, hospital discharge and 3 months postoperatively, BDI-II scores, anxious symptoms, Beck Anxiety Inventory scores, Quality of Recovery-15 (QoR-15) scores, and 1- and 3-month mortality.Main resultsA total of 151 patients (75 in the esketamine group and 76 in the normal saline group) completed the 1-month follow-up. The esketamine group had a significantly lower incidence of depressive symptoms at 1 month compared to the normal saline group (1.3% vs. 11.8%; risk difference = −10.5, 95%CI = −19.6% to −0.49%; p = 0.018). After excluding patients without lung cancer diagnosis, the incidence of depressive symptoms was also lower in the esketamine group (1.4% vs. 12.2%; risk difference = −10.8, 95%CI = −20.2% to −0.52%; p = 0.018). The secondary outcomes were similar between groups, except that the esketamine group had higher QoR-15 scores at 1 month postoperatively (median difference = 2; 95%CI = 0 to 5; p = 0.048). The independent risk factors for depressive symptoms were hypertension (odds ratio = 6.75, 95%CI = 1.13 to 40.31; p = 0.036) and preoperative anxious symptoms (odds ratio = 23.83, 95%CI = 3.41 to 166.33; p = 0.001).ConclusionPerioperative administration of esketamine reduced the incidence of depressive symptoms at 1 month after thoracoscopic lung cancer surgery. History of hypertension and preoperative anxious symptoms were independent risk factors for depressive symptoms.Clinical trial registration: Chinese Clinical Trial Registry http://www.chictr.org.cn, Identifier (ChiCTR2100046194).

Introduction Opioid-free anaesthesia (OFA) may reduce opioid-related side effects such as postoperative nausea and vomiting (PONV) and hyperalgesia. This study aims to investigate the effects of balanced OFA on PONV and pain outcomes in patients undergoing video-assisted thoracoscopic surgery (VATS).Methods and analysis This randomised controlled trial will be conducted at the First Affiliated Hospital of Soochow University in Suzhou, China. A total of 120 adults scheduled for VATS lung resection will be randomly assigned with a 1:1 ratio to either an OFA group or a control group, stratified by sex (n=60 in each group). Patients will receive balanced anaesthesia with esketamine, dexmedetomidine and sevoflurane (the OFA group), or sufentanil and sevoflurane (the control group). All patients will receive PONV prophylaxis with intraoperative dexamethasone and ondansetron. Multimodal analgesia consists of intraoperative flurbiprofen axetil, ropivacaine infiltration at the end of surgery and postoperative patient-controlled sufentanil. The primary outcome is the incidence of PONV within 48 hours after surgery. Secondary outcomes are nausea, vomiting, need for antiemetic therapy, pain scores at rest and while coughing, postoperative sufentanil consumption, need for rescue analgesia, length of post-anaesthesia care unit stay, length of postoperative hospital stay, and 30-day and 90-day post-surgical pain and mortality. Safety outcomes are hypotension, bradycardia, hypertension, tachycardia, interventions for haemodynamic events, level of sedation, headache, dizziness, nightmare and hallucination. All analyses will be performed in the modified intention-to-treat population.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of the First Affiliated Hospital of Soochow University (2022-042). All patients will provide written informed consent. The results of this study will be published in a peer-reviewed journal.Trial registration number Chinese Clinical Trial Registry (ChiCTR2200059710).

Background: The mechanisms underlying myocardial ischemia/reperfusion (I/R) injury are not fully understood. This study aims to explore key candidate genes and potential therapeutic targets for treatment of myocardial I/R injury.Methods: The transcriptional profiles of ventricular myocardium during cardiac arrest, ischemia, and reperfusion were obtained from the Gene Expression Omnibus database. Based on the transcriptional data of GSE6381, functional pathway and process enrichment analyses, protein–protein interaction network, and gene set enrichment analyses were conducted. In the animal experiments, we established the myocardial I/R injury model in mice. We validated the mRNA and protein expression of the key genes using the qPCR and western blots. We further assessed the expression and localization of CCL21 and its receptors using immunofluorescence staining experiments.Results: The microarray analyses identified five key genes (CCL21, XCR1, CXCL13, EDN1, and CASR). Myocardial I/R process in mice resulted in significant myocardial infraction, histological damage, and myocardial apoptosis. The results of qPCR and western blots showed that the expression of CCL21 and CXCL13 were increased following myocardial I/R injury in mice. Furthermore, the immunofluorescence staining results revealed that the expression of GPR174/CCR7 (CCL21 receptors), but not CXCR5 (CXCL13 receptor), was elevated following myocardial I/R injury. Moreover, the activated CCL21-GPR174/CCR7 signaling was located on the cardiac fibroblasts of the myocardium with I/R injury.Conclusion: This study revealed several key factors underlying myocardial I/R injury. Of these, the activation of CCL21-GPR174/CCR7 signaling on cardiac fibroblasts was highlighted, which provides potential therapeutic targets for cardioprotection.

BackgroundOpioid-free anesthesia (OFA) may improve postoperative outcomes by reducing opioid-related adverse effects. This study aims to evaluate the effects of OFA on postoperative nausea and vomiting (PONV), postoperative pain, and 30-day outcomes after thyroid and parathyroid surgery.MethodsThis two-center, randomized, double-blind, controlled trial will include 400 adult patients scheduled for thyroid and parathyroid surgery. Patients will be randomly assigned, 1:1 and stratified by sex and site, to an OFA group (esketamine, lidocaine, and dexmedetomidine) or a control group (opioid-based anesthesia with sufentanil). All patients will receive propofol-based total intravenous anesthesia and PONV prophylaxis with dexamethasone and ondansetron. The primary outcome is the incidence of PONV (defined as experiencing any event of nausea, retching, or vomiting) during the first 48 h postoperatively. The secondary outcomes include the severity of PONV, antiemetic rescue therapy, pain scores at rest and while coughing, need for rescue analgesia, perioperative adverse effects related to anesthetics or analgesics (hypotension, bradycardia, hypertension, tachycardia, desaturation, dizziness, headache, hallucination, and nightmare), time to extubation, length of post-anesthesia care unit stay, length of postoperative hospital stay, patient satisfaction, and a composite of 30-day major adverse events (myocardial infarction, cardiac arrest, cerebrovascular accident, coma, acute renal failure, pulmonary embolism, sepsis, septic shock, deep neck space infection, reintubation, reoperation, blood transfusion, failure to wean off ventilator, and death). Analyses will be performed in the modified intention-to-treat population.DiscussionWe hypothesize that our OFA regimen reduces PONV after thyroid and parathyroid surgery. We will also investigate whether OFA leads to improvements in postoperative pain and major adverse events. Our results will offer evidence for optimizing anesthesia regimens in patients who undergo thyroid and parathyroid surgical procedures.Clinical trial registrationhttp://www.chictr.org.cn, identifier: ChiCTR2200059656.

Ischemia-reperfusion (I/R) injury is a serious clinical pathology associated with acute kidney injury (AKI). Ferroptosis is non-apoptotic cell death that is known to contribute to renal I/R injury. Dexmedetomidine (Dex) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate the detailed molecular mechanism of Dex protects kidneys against I/R injury through inhibiting ferroptosis. We established the I/R-induced renal injury model in mice, and OGD/R induced HEK293T cells damage in vitro. RNA-seq analysis was performed for identifying the potential therapeutic targets. RNA-seq analysis for differentially expressed genes (DEGs) reported Acyl-CoA synthetase long-chain family member 4 (ACSL4) related to ferroptosis and inflammation in I/R mice renal, which was validated in rodent renal. Liproxstatin-1, the specific small-molecule inhibitor of ferroptosis, significantly attenuated ferroptosis-mediated renal I/R injury with decreased LPO, MDA, and LDH levels, and increased GSH level. Inhibiting the activity of ACSL4 by the Rosiglitazone (ROSI) resulted in the decreased ferroptosis and inflammation, as well as reduced renal tissue damage, with decreasing LPO, MDA and LDH level, increasing GSH level, reducing COX2 and increasing GPx4 protein expression, and suppressing the TNF-α mRNA and IL-6 mRNA levels. Dex as a α2-adrenergic receptor (α2-AR) agonist performed renal protective effects against I/R-induced injury. Our results also revealed that Dex administration mitigated tissue damage, inhibited ferroptosis, and downregulated inflammation response following renal I/R injury, which were associated with the suppression of ACSL4. In addition, ACSL4 overexpression abolishes Dex-mediated protective effects on OGD/R induced ferroptosis and inflammation in HEK293T cells, and promotion of ACSL4 expression by α2-AR inhibitor significantly reversed the effects on the protective role of Dex. This present study indicated that the Dex attenuates ferroptosis-mediated renal I/R injury and inflammation by inhibiting ACSL4 via α2-AR.

Abstract Background The Surgical Pleth Index (SPI) is a monitoring method that reflects painful stimuli during general anesthesia, and dexmedetomidine is an analgesic adjuvant with an opioid-sparing effect. But up to now, it is still unclear whether dexmedetomidine has any influence on SPI. To investigate whether dexmedetomidine has an effect on SPI during video-assisted thoracoscopic surgery. Methods We enrolled 94 patients who underwent video-assisted thoracoscopic lung lobectomy. Patients were randomly assigned to a dexmedetomidine group (dexmedetomidine: 0.8 μg/kg administered for 10 min before anesthesia) or normal saline group (equal volume of normal saline). SPI and vital signs were recorded. The number rating scale (NRS) pain score was also evaluated. Results SPI values were significantly lower in the dexmedetomidine group than in the normal saline group at intubation and at discharge from the postanesthesia care unit. Compared with the normal saline group, mean arterial pressure and heart rate were both significantly lower in the dexmedetomidine group at intubation. Heart rate was lower at skin incision in the dexmedetomidine group. The NRS score in the normal saline group was noticeably higher vs. the dexmedetomidine group at discharge from the postanesthesia care unit. Conclusions Dexmedetomidine decreased intraoperative SPI and NRS scores. Our results showed that dexmedetomidine attenuated noxious stimuli. Trial registration Chinese Clinical Trial Registry (ChiCTR): ChiCTR-OOC-16009450 , Registered 16 October, 2016.

BackgroundVideo-assisted thoracoscopic surgery (VATS) has been widely performed for patients with lung cancer. Splenic rupture after VATS lung procedures is a very rare and serious event.Case PresentationWe reported a case with hemodynamic instability after left lower VATS lobectomy. There was no evidence of diaphragmatic injury during the surgery. Computed tomography (CT) showed spleen injury and large amount of fluid in the abdominal cavity. Emergent laparotomy was performed, and splenic rupture was diagnosed. The patient underwent splenectomy, with two lacerations at the diaphragmatic surface of the spleen. The patient did well postoperatively and was discharged from the hospital on postoperative day 5.ConclusionThere are few similar cases reported in the literature. Persistent hemodynamic instability due to the rupture of spleen is life-threatening. In the situation of unexplained hypotension during VATS procedures (especially left-sided approaches), the possibility of splenic injury and rupture should be considered. Abdominal ultrasonography and/or CT examinations should be carried out for prompt diagnosis and treatment of such rare complication.

Background: Same-day esophagogastroduodenoscopy and colonoscopy procedures under sedation have been increasingly performed. This study aims to assess the effects of esketamine combined with ciprofol (a novel anesthetic/sedative agent) or propofol on respiratory and hemodynamic adverse events in patients undergoing same-day bidirectional endoscopy.Methods: This is a prospective, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. A total of 180 adult patients scheduled for same-day bidirectional endoscopy under sedation will be randomized, in a 1:1:1:1 ratio, to receive 1 of 4 sedation regimens: 1) ciprofol and esketamine, 2) propofol and esketamine, 3) ciprofol and normal saline placebo, or 4) propofol and normal saline placebo. The primary outcome is a composite of desaturation [peripheral oxygen saturation (SpO2) < 95%] and hypotension [mean blood pressure (MBP) < 65 mmHg or decrease in MBP ≥20% of baseline] during the sedation and in the recovery room. Secondary outcomes include episodes of desaturation, severe desaturation (SpO2 < 90%), hypotension, severe hypotension (decrease in MBP ≥30% of baseline), bradycardia, postoperative nausea and vomiting, dizziness or headache, hallucination or nightmare, injection pain, pain scores and fatigue scores, endoscopist satisfaction, and patient satisfaction. Data will be analyzed on the modified intention-to-treat basis.Discussion: We hypothesize that esketamine as an adjuvant to ciprofol or propofol sedation would improve cardiorespiratory stability. In addition, the potential interactions between interventions will be explored using the factorial design. The results of this trial will provide evidence for daily practice of sedation regimens for same-day bidirectional endoscopy.Clinical Trial Registration: Chinese Clinical Trials Registry, Identifier ChiCTR2100052523.

Background: NLRP3 inflammasome contributes a lot to sterile inflammatory response and pyroptosis in ischemia/reperfusion (I/R) injury. Cardiac fibroblasts (CFs) are regarded as semi-professional inflammatory cells and they exert an immunomodulatory role in heart. Iguratimod provides a protective role in several human diseases through exerting a powerful anti-inflammatory effect. However, it is still unclear whether iguratimod could alleviate myocardial I/R injury and whether inflammation triggered by NLRP3-related pyroptosis of CFs is involved in this process.Methods: Transcriptomics analysis for GSE160516 dataset was conducted to explore the biological function of differentially expressed genes during myocardial I/R. In vivo, mice underwent ligation of left anterior descending coronary artery for 30 min followed by 24 h reperfusion. In vitro, primary CFs were subjected to hypoxia for 1 h followed by reoxygenation for 3 h (H/R). Iguratimod was used prior to I/R or H/R. Myocardial infarct area, serum level of cardiac troponin I (cTnI), pathology of myocardial tissue, cell viability, lactate dehydrogenase (LDH) release, and the expression levels of mRNA and protein for pyroptosis-related molecules were measured. Immunofluorescence was applied to determine the cellular localization of NLRP3 protein in cardiac tissue.Results: During myocardial I/R, inflammatory response was found to be the most significantly enriched biological process, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling was a crucial pathway in mediating cardiac inflammation. In our experiments, pretreatment with iguratimod significantly ameliorated I/R-induced myocardial injury and H/R-induced pyroptosis of CFs, as evidenced by reduced myocardial infarct area, serum cTnI level, and LDH release in supernatants, as well as improved pathology of cardiac tissue and cell viability. Immunofluorescence analysis showed that NLRP3 was mainly localized in CFs. Moreover, iguratimod inhibited the expression of pro-inflammatory cytokines and pyroptosis-related molecules, including NLRP3, cleaved caspase-1, and GSDMD-N.Conclusion: Our results suggested that inflammatory response mediated by NOD-like receptor signaling is of vital importance in myocardial I/R injury. Iguratimod protected cardiomyocytes through reducing the cascade of inflammation in heart by inhibiting cardiac fibroblast pyroptosis via the COX2/NLRP3 signaling pathway.

Background: Older hypertensive adults are at increased risk for postoperative morbidity and mortality. As first line antihypertensive drug therapy, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have many beneficial effects. However, the use of ACEIs/ARBs in the perioperative period remains controversial. This study aims to determine the effects of withholding vs. continuing ACEIs/ARBs before non-cardiac surgery on perioperative hypotension and postoperative outcomes in older patients.Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, a total of 2036 patients aged 60–80 years undergoing non-cardiac surgical procedures will be randomly assigned, in a 1:1 ratio, to receive oral ACEIs/ARBs (the ACEIs/ARBs continued group) or inactive placebos (the ACEIs/ARBs withheld group) on the morning of surgery. For both groups, the ACEIs/ARBs will be continued from the first postoperative day. The primary outcome measure is the incidence of perioperative hypotensive events, defined as mean blood pressure (MBP) < 65 mmHg or ≥30% reduction in MBP from baseline during surgery and in a post-anesthesia care unit. The secondary outcomes include duration of perioperative hypotension, intraoperative use of fluids and vasopressors, hypotensive events within postoperative 3 days, and perioperative neurocognitive disorders, major adverse cardiocerebral events (a composite outcome of stroke, coma, myocardial infarction, heart block, and cardiac arrest), and mortality within 30 days after surgery.Discussion: The results of this trial will offer an evidence-based perioperative ACEIs/ARBs therapy for older hypertensive adults undergoing non-cardiac surgery.Study Registration: This study is approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University (Approval No. 2020-077-1) and by the institutional ethics review board of each participating center. This protocol is registered at the Chinese Clinical Trials Registry (ChiCTR2000039376).

Premedication is important in pediatric anesthesia. This meta-analysis aimed to investigate the role of dexmedetomidine as a premedicant for pediatric patients. A systematic literature search was conducted to identify randomized controlled trials comparing dexmedetomidine premedication with midazolam or ketamine premedication or placebo in children. Two reviewers independently performed the study selection, quality assessment and data extraction. The original data were pooled for the meta-analysis with Review Manager 5. The main parameters investigated included satisfactory separation from parents, satisfactory mask induction, postoperative rescue analgesia, emergence agitation and postoperative nausea and vomiting. Thirteen randomized controlled trials involving 1190 patients were included. When compared with midazolam, premedication with dexmedetomidine resulted in an increase in satisfactory separation from parents (RD = 0.18, 95% CI: 0.06 to 0.30, p = 0.003) and a decrease in the use of postoperative rescue analgesia (RD = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003). Children treated with dexmedetomidine had a lower heart rate before induction. The incidence of satisfactory mask induction, emergence agitation and PONV did not differ between the groups. Dexmedetomidine was superior in providing satisfactory intravenous cannulation compared to placebo. This meta-analysis suggests that dexmedetomidine is superior to midazolam premedication because it resulted in enhanced preoperative sedation and decreased postoperative pain. Additional studies are needed to evaluate the dosing schemes and long-term outcomes of dexmedetomidine premedication in pediatric anesthesia.

Background: Sedation of pediatric patients undergoing cerebral angiography is challenging. Although dexmedetomidine is used for sedation in various procedures, it has not been reported for pediatric patients undergoing cerebral angiography. This study compared the safety and efficacy of dexmedetomidine with that of propofol for cerebral angiography in pediatric patients. Materials and Methods: Sixty-two patients (6-15 years) scheduled for elective cerebral angiography were apportioned randomly and equally to receive either propofol or dexmedetomidine sedation. Patients in the propofol group received an initial bolus of intravenous propofol (1 mg/kg) and a maintenance infusion of 100 μg/kg/min. Patients in the dexmedetomidine group received an initial bolus of intravenous dexmedetomidine (1 μg/kg over 10 min) and a maintenance infusion of 1 μg/kg/h. An additional bolus of propofol 0.5 mg/kg or dexmedetomidine 0.25 μg/kg was repeated if needed. Procedure time, time to recovery and adverse events associated with sedation were recorded. Results: All cerebral angiographies were completed successfully under sedation with dexmedetomidine or propofol. Mean cerebral angiography time was 36 ± 10 min in the propofol group and 31 ± 7 min in the dexmedetomidine group (P = 0.047). The percentage of airway events and total adverse events were significantly higher in the propofol group (P < 0.05). Heart rate decreased in the dexmedetomidine group and mean arterial pressure decreased in the propofol group (P < 0.05, each). Conclusion: Although cerebral angiography can be performed successfully under sedation with either propofol or dexmedetomidine, dexmedetomidine may be a better alternative because of fewer respiratory adverse events.

AIMS:To investigate whether dexmedetomidine (DEX) preconditioning could alleviate the inflammation caused by myocardial ischemia/reperfusion (I/R) injury by reducing HMGB1-TLR4-MyD88-NF-кB signaling. METHODS:Seventy rats were randomly assigned into five groups: sham group, myocardial I/R group (I/R), DEX+I/R group (DEX), DEX+yohimbine+I/R group (DEX/YOH), and yohimbine+I/R group (YOH). Animals were subjected to 30 min of ischemia induced by occluding the left anterior descending artery followed by 120 min of reperfusion. Myocardial infarct size and histological scores were evaluated. The levels of IL-6 and TNF-α in serum and myocardium were quantified by enzyme-linked immunosorbent assay, and expression of HMGB1, TLR4, MyD88, IκB and NF-κB in the myocardial I/R area were determined with Western blot and immunocytochemistry. RESULTS:Myocardial infarct sizes, histological scores, levels of circulating and myocardial IL-6 and TNF-α, the expression of HMGB1, TLR4, MyD88 and NF-κB, and the degradation of IκB were significantly increased in the I/R group compared with the sham group (P

Coronary artery bypass graft (CABG) is associated with a high risk of mortality and morbidity; thus, assessment of surgery quality is necessary. In this perspective, we will focus on the structure, process, and outcomes measured as quality assessment. A set of 21 evidence-based structure, process, and outcome measures were selected as National Quality Forum. Of these, the Society of Thoracic Surgeons ultimately chose 11 individual quality measures grouped them into four domains used to assess the quality of CABGs. These four domains consisted of perioperative medical care, operative care, risk-adjusted operative mortality and postoperative risk-adjusted major morbidity. These measures have been useful as quality improvement tools in assessing the quality of CABG surgery. [ABSTRACT FROM AUTHOR]