Background: Ventilation management during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is challenging because of shared airway use and the risks of hypoxaemia and hypercapnia. This study compared the safety and efficacy of superimposed high-frequency jet ventilation (SHFJV) and pressure-controlled ventilation (PCV) using a supraglottic airway (SGA) under general anaesthesia. Methods: Patients undergoing EBUS-TBNA were randomly assigned to receive either SHFJV or PCV. The primary outcomes was perioperative changes in oxygenation index (OI). Secondary outcomes included intraoperative hypoxaemia and hypercapnia, perioperative changes pressure of carbon dioxide (PaCO2), haemodynamic stability, intraoperative and postoperative adverse events (AEs), and SGA ventilation quality. Results: All 88 patients (28.4 % female; median age, 62 years) were analysed. Overall, 44 participants were randomised to SHFJV, and 44 participants were randomised to PCV. Post-hoc analysis showed that the SHFJV group had significantly greater improvement in OI at the end of surgery (mean difference (MD) = 78.52, 95 % confidence interval (CI), 30.35 to 126.68), P = 0.039) and a significant decrease in PaCO2 after 19 min (MD =-8.23, 95 % CI =-12.68 to-3.77, P = 0.001). Intraoperative and postoperative adverse events were similar between the groups, and no significant differences were observed in intraoperative hypoxaemia or hypercapnia. The SHFJV group had fewer cases of poor SGA ventilation quality (4.5 %) than the PCV group (20 %), demonstrating superior SGA ventilation quality (P = 0.024). Conclusions: SHFJV significantly improved OI compared with PCV while maintaining comparable safety profiles during EBUS-TBNA. These findings underscore the SHFJV as a promising ventilation strategy, particularly for patients requiring improved oxygenation during complex airway interventions. Registration: Chinese Clinical Trial Registry; Registration number: ChiCTR2300071799; URL: https://www.ch ictr.org.cn/showproj.html?proj=197551.
Maladaptive changes in gene expression at transcriptional level in dorsal root ganglia (DRGs) after nerve injury are critical for neuropathic pain genesis. Emerging evidence reveals the important role of non-coding RNAs (ncRNAs) in regulating gene transcription. Recent studies also have showed the contribution of ncRNAs to neuropathic pain. However, the expression profile of ncRNAs in the DRGs and potential regulatory mechanism in peripheral nerve injury-induced neuropathic pain are not fully clear. We used bCCI neuropathic pain model induced by chronic constriction injury of bilateral sciatic nerves to study the expression profile and potential functional mechanism of micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and messenger RNA (mRNA) in the DRGs by RNA sequencing and bioinformatics analysis. A total of 47 miRNAs, 337 lncRNAs, 32 circRNAs, and 2269 mRNAs were differentially expressed (DE) in the DRGs of CCI mice 14 days after surgery. KEGG analysis demonstrated nociception-related signaling pathways were significantly enriched for DEncRNAs, including Rap1, Ras, and Hippo signaling pathway. GO analysis showed neuron related biological process, membrane related cell components, and binding related molecular functions were significantly enriched. The competing endogenous RNA (ceRNA) regulatory network of DEmiRNA-DEmRNA, DElncRNA-DEmRNA, and DEcircRNA-DEmiRNA existed in the DRGs of mice with neuropathic pain induced by peripheral nerve injury. In addition, 81 pain-related DE genes had protein–protein interactions (PPI) with each other. Our findings indicated that ncRNAs are involved in the development of peripheral nerve injury-induced neuropathic pain. DEncRNAs may provide us with a new perspective in chronic neuropathic pain research and may become a potential target for pain treatment.
Abstract Objective Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients. Method This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models. Results Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p < 0.001). Logistic regression analysis showed that CatB, S100-A9, VCAM-1, prosaposin, and NGAL could be used for preoperative diagnosis and postoperative prediction of organ dysfunction. CatB and S100-A9 were possible predictive factors for preoperative diagnosis of renal failure in septic patients. Internal validation was assessed using the bootstrapping validation. The preoperative diagnosis of renal failure model displayed good discrimination with a C-index of 0.898 (95% confidence interval 0.843–0.954) and good calibration. Conclusion Serum CatB, S100-A9, VCAM-1, prosaposin, and NGAL may be novel markers for preoperative diagnosis and postoperative prediction of organ dysfunction. Specifically, S100-A9 and CatB were indicators of preoperative renal dysfunction in septic patients. Combining these two biomarkers may improve the accuracy of predicting preoperative septic renal dysfunction. Trial registration The study was registered at the Chinese Clinical Trials Registry (ChiCTR2200060418) on June 1, 2022.
Introduction Surgeries conducted at night can impact patients’ prognosis, and the mechanism may be related to circadian rhythm, which influence normal physiological functions and pathophysiological changes. Melatonin is primarily a circadian hormone with hypnotic and chronobiotic effects, thereby affecting disease outcomes through influencing the expression of inflammatory factors and biochemical metabolism. This study aims to observe the effects of circadian rhythms on emergence agitation and early postoperative delirium of older individuals undergoing thoracoscopic lung cancer surgery and explore the possible regulatory role of melatonin. Methods This prospective, observational, cohort study will involve 240 patients. Patients will be routinely divided into three groups based on the time of the surgery: T1 (8:00–14:00), T2 (14:00–20:00) and T3 group (20:00–08:00). The primary outcome will be the incidence of emergence agitation assessed via the Richmond Agitation and Sedation Scale (RASS) in the post-anesthesia care unit (PACU). Secondary outcomes will include the incidence of early postoperative delirium assessed via the Confusion Assessment Method (CAM) on postoperative day 1, pain status assessed via the numerical rating scale (NRS) in the PACU, sleep quality on postoperative day 1 and changes in perioperative plasma melatonin, clock genes and inflammatory factor levels. Postoperative surgical complications, intensive care unit admission and hospital length of stay will also be evaluated. Discussion This paper describes a protocol for investigating the effects of circadian rhythms on emergence agitation and early postoperative delirium of older individuals undergoing thoracoscopic lung cancer surgery, as well as exploring the potential regulatory role of melatonin. By elucidating the mechanism by which circadian rhythms impact postoperative recovery, we aim to develop a new approach for achieving rapid recovery during perioperative period. Trial registration The study was registered at the Chinese Clinical Trials Registry (ChiCTR2000040252) on November 26, 2020, and refreshed on September 4, 2022.
Background: The authors aim to investigate the effect of music on hemodynamic fluctuations during induction of general anesthesia and reducing preoperative anxiety for women who underwent elective non-cardiac surgery. Methods: It is a multicenter, double-blind, randomized, parallel-group clinical trial. Patients were randomized 1:1 to either a Music Intervention group (MI) or a Control group (Control). The MI participants listened to their preferred music for more than 30 minutes in the waiting area. The State-Trait Anxiety Inventory (STAI) was used to measure anxiety levels in the groups, and hemodynamic parameters (Heart Rate [HR], Mean Arterial Pressure [MAP]) were continuously recorded before induction (T0), at loss of consciousness (T1), immediately before intubation (T2), and after intubation (T3). Intubation-related adverse events were also recorded. The primary outcome was the incidence of MAP changes more than 20 % above baseline during T0-T2. Results: A total of 164 patients were included in the final analyses. The incidence of MAP instability during T0-T2 was lower in the MI, and the 95 % Confidence Interval for the rate difference demonstrated the superiority of MI. HR instability was less frequent in MI participants both in T0-T2 and T2-T3. The overall incidence of preoperative anxiety was 53.7% (88/164). After the music intervention, the mean score of STAI was significantly lower in the MI than in the Control, with a between-group difference of 8.01. Conclusions: Preoperative music intervention effectively prevented hemodynamic instability during anesthesia induction and significantly reduced preoperative anxiety in women undergoing elective non-cardiac surgery.
Background: Cardiovascular surgeries often require deep hypothermic circulatory arrest and cardiopulmonary bypass (CPB), which can disrupt blood clotting and lead to excessive bleeding. Traditional treatments involve transfusing blood and blood products, which can have adverse effects and place significant strain on the global blood supply. Research suggests that autologous platelet-rich plasmapheresis (aPRP) may reduce the need for transfusions by preserving blood components. However, the impact of aPRP on postoperative blood loss and clinical outcomes in cardiovascular surgery remains controversial. This study aimed to examine the effects of aPRP on postoperative blood loss and recovery in patients undergoing heart valve surgery. Methods: A total of 183 patients were divided into either aPRP or control groups. The aPRP group received aPRP before CPB, whereas the control group did not. The primary endpoint was postoperative bleeding between the groups. The secondary endpoints were postoperative bleeding risk factors and clinical outcome assessment. Logistic regression analysis with covariate adjustment was used to calculate these risk factors. Results: A total of 76 patients (41.5%) in the aPRP group and 107 patients (58.5%) in the control group were included in the analysis. No significant difference was found in the occurrence of postoperative bleeding [odds ratio (OR) =0.53, 95% confidence interval (CI): 0.28-1.00, P=0.05], and the aPRP group had fewer complications than the controls (OR =0.28, 95% CI: 0.10-0.68, P=0.009). However, after adjusting for the New York Heart Association (NYHA) classification, diabetes, arrhythmology, mean activated clotting time (ACT mean ), CPB, bleeding, thoracotomy, and body mass index (BMI), there was a significant difference in postoperative bleeding (adjusted OR =0.47, 95% CI: 0.22-0.98, P=0.04) and complications (adjusted OR =0.23, 95% CI: 0.07-0.64, P=0.008) between the two groups. Conclusions: Preoperative aPRP can improve postoperative outcomes and reduce complications in patients undergoing heart valve surgery.
BACKGROUND:Remimazolam tosilate (RT) is a novel short-acting GABA (A) receptor agonist that has a rapid recovery from procedural sedation and can be fully reversed by flumazenil. To date, there have been relatively few articles comparing RT and propofol for general anesthesia. This study aimed to assess the efficacy and safety of RT with or without flumazenil compared with propofol in general anesthesia for day surgery. METHODS:115 patients scheduled for day surgery were randomized into three groups: RT (n = 39), RT + flumazenil (n = 38) and propofol (n = 38). The primary endpoints were anesthesia induction time and time until fully alert. Anesthesia success rate, bispectral index (BIS) values, injection pain, opioid and vasopressor dosages, postoperative recovery profiles and perioperative inflammatory and cognitive changes were assessed. Any adverse events were recorded. RESULTS:Induction times were similar among the three groups (P = 0.437), but the median time until fully alert in patients treated with RT was longer than that of the propofol or RT + flumazenil groups (17.6 min vs. 12.3 min vs. 12.3 min, P < 0.001). The three groups had comparable postoperative recovery quality and inflammatory and cognitive state changes (P > 0.05). Smaller percentages of patients who received RT (26.3%) and RT + flumazenil (31.6%) developed hypotension during anesthesia maintenance compared with propofol (68.4%), and consequently less ephedrine (P < 0.001) and phenylephrine (P = 0.015) were needed in the RT group. Furthermore, serum triglyceride levels were lower (P < 0.001) and injection pain was much less frequent in the RT with or without flumazenil groups compared with the propofol group (5.3% vs. 0% vs. 18.4%). CONCLUSION:RT permits rapid induction and comparable recovery profile compared with propofol in general anesthesia for day surgery, but has a prolonged recovery time without flumazenil. The safety profile of RT was superior to propofol in terms of hypotension and injection pain. TRIAL REGISTRATION:The study was registered at Chinese Clinical Trial Registry http://www.chictr.org.cn/ (Registration date: 19/7/2021; Trial ID: ChiCTR2100048904).
Background The pathogenesis of neuropathic pain (NP) has not been fully elucidated. Gene changes in dorsal root ganglia (DRG) may contribute to the development of NP. Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that form covalently closed loop structures and are crucial for genetic and epigenetic regulation. However, little is known about circRNA changes in DRG neurons after peripheral nerve injury. Methods A sciatic nerve chronic constriction injury (CCI) model was established to induce neuropathic pain. We performed genome-wide circRNA analysis of four paired dorsal root ganglion (DRG) samples (L4-L5) from CCI and negative control (NC) rats using next-generation sequencing technology. The differentially expressed circRNAs (DEcircRNAs) were identified by differential expression analysis, and the expression profile of circRNAs was validated by quantitative PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of DEcircRNAs. Results A total of 374 DEcircRNAs were identified between CCI and NC rats using circRNA high-throughput sequencing. Among them, 290 were upregulated and 84 were downregulated in the CCI group. The expression levels of nine DEcircRNAs were validated by qPCR. Functional annotation analysis showed that the DEcircRNAs were mainly enriched in pathways and functions, including 'dopaminergic synapse,' 'renin secretion,' 'mitogen-activated protein kinase signaling pathway,' and 'neurogenesis.' Competing endogenous RNA analysis showed that the top 50 circRNAs exhibited interactions with four pain-related microRNAs (miRNAs). Circ:chr2:33950934-33955969 was the largest node in the circRNA-miRNA interaction network. Conclusions Peripheral nerve injury-induced neuropathic pain led to changes in the comprehensive expression profile of circRNAs in the DRG of rats. DEcircRNAs may advance our understanding of the molecular mechanisms underlying neuropathic pain.
Objective:To explore the mechanism of autophagy in sevoflurane-induced neuronal apoptosis in the hippocampus of aged mice.Methods:According to the random number table method, sixteen 18-month-old BL/C57 mice were divided into two groups ( n=8): a sevoflurane group and a control group. The sevoflurane group inhaled 47.5% air+2.5% sevoflurane+50% oxygen for 3 h, while the control group inhaled 50% air+50% oxygen for 3 h. Then, 24 h after modeling, the novel object recognition experiment was performed, and the brains were removed to collect the hippocampus. Nissl staining was performed to detect the apoptosis of neurons in the hippocampus, and Western blot was used to detect the levels of autophagy-related proteins in neurons [microtubule-associated protein (LC3)Ⅱ/LC3Ⅰ, Becline-1, and p62]. Furthermore, according to the random number table method, eighteen 18-month-old BL/C57 mice were divided into three groups ( n=6): a sevoflurane+3-methyladenie group (group M, intraperitoneal injection of 3-methyladenine 2 h before inhaling anesthesia), a sevoflurane+rapamycin group (group R, intraperitoneal injection of rapamycin 24 h and 2 h before inhaling anesthesia), and a sevoflurane+normal saline group (group N, intraperitoneal injection of 100 μl normal saline 2 h before inhaling anesthesia). After intraperitoneal injection and sevoflurane treatment, Nissl staining was used to detect the apoptosis of hippocampal neurons, and Western blot was used to detect the level of autophagy related proteins (LC3Ⅱ/LC3Ⅰ, Becline-1, p62) in hippocampal neurons. Results:Compared with the control group, the sevoflurane group showed significant decreases in the recognition rate and resolution coefficient of novel objects ( P<0.05), increases in hippocampal neuronal apoptosis ( P<0.05), increases in the levels of LC3Ⅱ/LC3Ⅰ and Becline-1 ( P<0.05), and decreases in the amounts of p62 protein ( P<0.05). Compared with group N, group M presented decreases in the levels of LC3Ⅱ/LC3Ⅰ and Becline-1 ( P<0.05), increases in the amounts of p62 ( P<0.05), and increases in neuronal apoptosis in the hippocampus ( P<0.05); group R presented increases in the levels of LC3Ⅱ/LC3Ⅰ and Becline-1 ( P<0.05), decreases in the amounts of p62 ( P<0.05), and decreases in neuronal apoptosis in the hippocampus ( P<0.05). Conclusions:After sevoflurane inhalation, aged mice show decreases in the recognition rate and resolution coefficient of new objects, and increases in neuronal apoptosis in the hippocampus, with activation of autophagy at the same time, which negatively inhibits neuronal apoptosis and exerts a neuroprotective effect.
Introduction Enhanced Recovery After Surgery (ERAS) protocols have been proven to promote postoperative recovery. However, limited evidence is available on ERAS protocols in patients undergoing peroral endoscopic myotomy (POEM). Aim To study the safety and effectiveness of an ERAS protocol in terms of the standard postoperative length of stay (LOS) and QoR-15 (Quality of Recovery) score of patients undergoing POEM. Material and methods Eighty patients were randomly divided into the ERAS or conventional group. The ERAS group received ERAS management, while the conventional group received normal management. The ERAS protocol included sufficient preoperative education, shortening time of preoperative fasting, maintaining intraoperative normothermia, intraoperative fluid management, and improving analgesia. We compared the results between the two groups in term of standard postoperative LOS and cost, QoR-15 score, postoperative pain and complications. Results Patients showed an improvement in the ERAS group in terms of earlier readiness for hospital discharge (40.21 ±8.42 h vs. 48.63 ±10.42 h; p < 0.001), earlier resumption of oral feeding (31.80 ±8.7 h vs. 42.35 ±10.80 h; p < 0.001), lower VAS, and higher QoR-15 score (139.29 ±2.21 vs. 137.03 ±3.77; p = 0.002) on postoperative day 2. For post-operative complications, there was no significant difference between the two groups. Conclusions The ERAS protocol is feasible and safe for POEM, and may decrease standard postoperative LOS, shorten recovery of gastrointestinal function, and improve postoperative patient satisfaction.
Background Hepatocellular carcinoma (HCC) is characterized by the neo-angiogenesis induced by tumor and adjacent cells. It is a leading cancer-related cause of death. Morphine has effects on angiogenesis with pro-angiogenic or anti-angiogenic phonotypes. This study explores the function of morphine on cancer cell growth, angiogenesis and the underlying mechanism in HCC. Methods Morphine was used to treat BEL-7402 or HCC-LM3 cells and human umbilical vein endothelial cells (HUVECs) were subsequently incubated in the conditioned media (CM) of HCC cells. The potential effects of cell proliferation, migration and tube formation of CM-treated HUVECs were investigated. Furthermore, the angiogenesis regulated factors of VEGFA, PIGF, ANG-1, ANG-2, FGF-1 and FGF-2 were assessed. siRNA and LY294002 were further used to explore the mechanism mediating the effects of morphine on the angiogenesis pathway. The neovascularization effect by morphine was confirmed through the use of human HCC cancer heterotopic mouse model in vivo. Results A significantly increased cell proliferation, migration, and tube formation effect of HUVECs induced by the CM from HCC cell lines treated with morphine was observed. More VEGFA secretion in CM from LM3 or BEL-7402 cell lines was found than the controls (P=0.03 and P=0.027, respectively). VEGFA knock-down could significantly reverse cell proliferation, migration and tube formation induced by the CM from HCC cell lines with morphine treatment. Further molecular experiments indicated that VEGFA secretion was activated by morphine potentially through the PI3K/Akt/HIF-1α pathway. Morphine-induced neovascularization was also observed by the IHC of CD31 and VEGFA. Conclusions Morphine promotes angiogenesis in hepatocellular carcinoma possibly through the activation of the PI3K/Akt/HIF-1α pathway and VEGFA stimulation.
Background : Circular RNAs (circRNAs) comprise a class of endogenous species of RNA consisting of a covalently closed loop structure that is crucial for genetic and epigenetic regulation. The significance of circRNA in neuropathic pain remains to be investigated. Methods : The sciatic nerve chronic constriction injury (CCI) model was established to induce neuropathic pain. We performed genome-wide circRNA analysis of 4 paired DRG sample from CCI and NC rats via next generation sequencing technology. The differentially expressed circRNAs (DEcircRNAs) were identified by differential expression analysis and the expression profile of circRNAs was validated by quantitative real-time PCR (qPCR). Functional annotation analysis was performed to predict the function of DEcircRNAs. Results : A total of 374 DEcirRNAs were identified between CCI and NC rats using circRNA High-throughput sequencing (HTS). Expression levels of 9 DEcircRNAs were validated by qPCR. Functional annotation analysis showed that DEcircRNAs were mainly enriched in pathways and functions such as ‘dopaminergic synapse’, ‘renin secretion’, ‘MAPK signaling pathway’ and ‘neurogenesis’. Competing endogenous RNAs analysis showed that top 50 circRNAs exhibited interactions with four pain related miRNAs. Circ:chr2:33950934-33955969 is the largest node in the circRNA-miRNA interaction network. Conclusion : DEcircRNAs may advance our understanding of the molecular mechanisms underlying neuropathic pain. Key words : neuropathic pain, circRNA, CCI, differential expression analysis
目的探讨七氟醚联合N2O吸入麻醉对老年大鼠短期及长期学习与记忆能力的影响。 方法将40只18月龄SD大鼠随机分配入麻醉组和对照组。麻醉组给予1.3%七氟醚+50% N2O吸入4 h,对照组给予50% O2吸入4 h。两组均于麻醉48 h后进行连续6 d的定航训练,并分别于第7、14天进行空间探索实验。水迷宫实验结束后,大鼠断头取脑,分别采用Western印迹法和免疫组化检测海马细胞凋亡情况。 结果麻醉组大鼠在第1次空间探索实验时,认知功能较对照组减退(P 结论七氟醚联合N2O吸入麻醉致老年大鼠认知功能障碍呈可逆性。
Hyperglycemia-mediated endothelial inflammation participates in the pathogenesis of cardiovascular complications in subjects with diabetes. Previous studies reported that phosphatase and tensin homolog deleted on chromosome ten (PTEN) and SET8 participate in high glucose-mediated endothelial inflammation. In this study, we hypothesize that SET8 regulates PTEN expression, thus contributing to high glucose-mediated vascular endothelial inflammation. Our data indicated that plasma soluble intercellular adhesion molecule-1 (sICAM-1) and endothelial selectin (e-selectin) were increased in patients with diabetes and diabetic rats. PTEN expression was augmented in the peripheral blood mononuclear cells of patients with diabetes and in the aortic tissues of diabetic rats. Our in vitro study indicated that high glucose increased monocyte/endothelial adhesion, endothelial adhesion molecule expression and p65 phosphorylation in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose led to endothelial inflammation via upregulation of PTEN. Furthermore, high glucose inhibited SET8 expression and histone H4 lysine 20 methylation (H4K20me1), a downstream target of SET8. SET8 overexpression reversed the effects of high-glucose treatment. shSET8-mediated endothelial inflammation was counteracted by siPTEN. Furthermore, SET8 was found to interact with FOXO1. siFOXO1 attenuated high glucose-mediated endothelial inflammation. FOXO1 overexpression-mediated endothelial inflammation was counteracted by siPTEN. H4K20me1 and FOXO1 were enriched in the PTEN promoter region. shSET8 increased PTEN promoter activity and augmented the positive effect of FOXO1 overexpression on PTEN promoter activity. Our in vivo study indicated that SET8 was downregulated and FOXO1 was upregulated in the peripheral blood mononuclear cells of patients with diabetes and the aortic tissues of diabetic rats. In conclusion, SET8 interacted with FOXO1 to modulate PTEN expression in vascular endothelial cells, thus contributing to hyperglycemia-mediated endothelial inflammation.
目的:探讨抗衰老酶1(sirtuin 1,SIRT1)在七氟醚(sevoflurane,Sev)联合一氧化二氮(N2O)吸入麻醉导致的原代海马神经元细胞凋亡中的作用.方法:原代海马神经元予以1.3%Sev联合50%N2 O吸入麻醉(对照组给予50%O2)处理2 h,或吸入麻醉前分别予以SIRT1拮抗剂sirtinol(50μmol/L)、salermide(50μmol/L)或激动剂resveratrol(100μmol/L)处理24 h.24 h后收集细胞,采用蛋白质印迹法检测Bax、剪切型半胱氨酸蛋白酶3(cleaved caspase-3,c-caspase-3)、剪切型聚腺苷酸二磷酸核糖转移酶[cleaved poly(ADP-ribose)polymerase,c-PARP]、磷酸化组蛋白H2A家族成员X(phosphorylated H2A histone family member X,γ-H2AX)、SIRT1和乙酰化p53[acetylated p53(lysine 381),acetyl-p53]蛋白水平,采用免疫荧光染色法检测c-caspase-3、SIRT1和acetyl-p53蛋白的分布及表达情况.结果:Sev联合N2 O吸入麻醉显著上调原代海马神经元中促凋亡蛋白Bax、c-caspase-3、c-PARP及DNA损伤相关指标γ-H2AX的表达水平(P<0.05);同时麻醉组SIRT1蛋白表达水平也显著升高,而acetyl-p53表达水平显著降低(P<0.05).吸入麻醉处理前给予SIRT1拮抗剂sirtinol或salermide预处理可抑制吸入麻醉引起的SIRT1蛋白表达上调,但增加了促凋亡蛋白Bax、c-caspase-3、c-PARP及DNA损伤指标γ-H2AX的表达(P<0.05);SIRT1激动剂预处理则呈现相反的结果(P<0.05).结论:Sev联合N2O吸入麻醉引起的SIRT1-p53信号通路激活可抑制其所致的原代海马神经元细胞凋亡.
Background: Catheterization of the axillary vein in the infraclavicular area has important advantages in patients with long-term, indwelling central venous catheters. The two most commonly used ultrasound-guided approaches for catheterization of the axillary vein include the long-axis/in-plane approach and the short-axis/out-of-plane approach, but there are certain drawbacks to both approaches. We have modified a new approach for axillary vein catheterization: the oblique-axis/in-plane approach. Methods: This observational study retrospectively collected data from patients who underwent ultrasound-guided placement of an axillary vein infusion port in the infraclavicular area at the Central Venous Access Clinics of Zhongshan Hospital at Fudan University between March 2014 and May 2017. The patients’ demographic data, success rate of catheterization, venous catheterization site, and immediate complications associated with catheterization were recorded. Results: Between March 2014 and May 2017, a total of 858 patients underwent placement of an axillary vein infusion port in the infraclavicular area at our center. The ultrasound-guided oblique-axis/in-plane approach was used for all patients, and the venipuncture success rate was 100%. Two cases of accidental arterial puncture and one case of local hematoma formation were reported, and no other complications, such as pneumothorax or nerve damage, were reported. Conclusion: The ultrasound-guided oblique-axis/in-plane approach is a safe and reliable alternative to the routine ultrasound-guided approach for axillary venous catheterization.
BACKGROUND:Postoperative cognitive dysfunction (POCD) seriously reduces quality of life and is associated with increased morbidity and mortality. The causes and neuropathogenesis of POCD remain largely unknown. Resveratrol, a sirtuin 1 (Sirt1) activator, is a polyphenol compound found in red wine that has protective functions in neuropathology paradigms. Endoplasmic reticulum stress (ERS) is a primary cellular response that activates the unfolded protein response (UPR). ERS and UPR mediate molecular and biochemical mechanisms related to neurodegeneration; however, the roles of ERS and Sirt1 in POCD remain unclear. The properties of resveratrol might be useful in the setting of POCD.METHODS:In the present study, we investigated learning and memory function and ERS pathways in aged mice after surgery under local anesthesia, and we evaluated the effects of resveratrol pretreatment.RESULTS:We found that resveratrol attenuated postoperative learning and memory impairment in aged mice postoperatively but did not alter locomotor activity. Resveratrol significantly decreased postoperative expression of ERS pathway UPR-related proteins and inflammatory mediators including nuclear factor-κB (NF-κB) in the hippocampus. This was accompanied by higher Sirt1 protein expression levels. Pretreatment with resveratrol did not affect the number of hippocampal neurons in aged mice after surgery.CONCLUSION:Overall, resveratrol pretreatment attenuated short-term learning and memory impairment and the ERS pathway UPR in aged mice after surgery under local anesthesia.
The aim of this study was to evaluate the effects of resveratrol on learning and memory impairment in aged rats after general anesthesia with sevoflurane and nitrous oxide (N2O), and explore the potential mechanism. 18-month-old Sprague-Dawley rats were randomly divided into anesthesia group (receiving 1.3% sevoflurane and 50% N2O for 4 hours) and control group. 48 hours after anesthesia, spatial learning and memory were tested by the Morris Water Maze experiment. The neurotoxicity and expression of silent information regulator 1 (SIRT1) in the hippocampus were measured. Moreover, the effect of resveratrol on spatial learning and memory after anesthesia in aged rats was also investigated. The results showed that general anesthesia triggered neuronal apoptosis and, subsequently, induced impairment of learning and memory ability. Neuronal apoptosis induced by anesthetics triggered endogenous SIRT1 expression. Moreover, the SIRT1 expression and p53 deacetylation was increased in rats pre-treated with resveratrol, which subsequently inhibited neuronal apoptosis and improved behavioral performance. In conclusion, our results demonstrated that general anesthesia with sevoflurane plus 50% N2O impaired learning and memory ability in aged rats, induced neuronal apoptosis and increased SIRT1 expression. Pretreatment with resveratrol improved the ability of learning and memory, inhibited neuronal apoptosis by increasing the expression of SIRT1 in aged rats after general anesthesia.
Neurocognitive deficits arising from anesthetic exposure have recently been debated, while studies have shown that the phosphorylation of cyclic AMP response element-binding protein (CREB) in the hippocampus is critical for long-term memory. To better understand the neural effects of inhalational anesthetics, we studied the behavioral and biochemical changes in aged rats that were exposed to sevoflurane (Sev) and nitrous oxide (N2O) for 4 h. Eighteen-month-old rats were randomly assigned to receive 1.3% sevoflurane and 50% nitrous oxide/50% oxygen or 50% oxygen for 4 h. Spatial learning and memory were tested with the Morris water maze 48 h after exposure, and the results showed that sevoflurane-nitrous oxide exposure induced a significant deficit in spatial learning acquisition and memory retention. Experiments revealed that the cAMP and pCREB levels in the dorsal hippocampus were decreased in rats with anesthetic exposure in comparison with control rats 48 h after anesthesia as well as 15 min after the probe trial, but there were no significant differences in CREB expression. Besides these, the current study also found the DG neurogenesis significantly decreased as well as neuronal loss and neuronal apoptosis increased in the hippocampus of rats exposed to Sev+N2O. The current study demonstrated that down-regulation of cAMP/CREB signaling, decrease of CREB-dependent neurogenesis and neuronal survival in the hippocampus contributed to the neurotoxicity and cognitive dysfunction induced by general anesthesia with sevoflurane-nitrous oxide.
Background: Postoperative shivering is a frequent complication of surgery in developing countries and there is no satisfying method to treat it, let alone to cure it. We studied whether intravenous amino acid (AA) infusion can cure postoperative shivering in the postanesthesia care unit.Methods: Sixty postanesthesia care unit patients with shivering grade 2 or higher and tympanic temperature <36 degrees C received randomly either infusion of Novamin 18 AAs (2 mL/kg/h), pethidine (0.5 mg/kg), or tramadol (1 mg/kg). Tympanic temperature, shivering grade, and thermal comfort were assessed every 5 min for 60 min. Blood glucose and lactic acid concentrations were measured before and after treatment. Postoperative nausea and vomiting were also recorded.Results: Shivering stopped within 5 min in the pethidine and tramadol groups versus 90% stopped within 15 min in AA group. There were five cases of reshivering in the tramadol group versus none in the AA or pethidine groups. Tympanic temperature increased slowly in all patients but increased significantly faster in the AA group. Thermal comfort improved significantly faster in the AA group versus the other two groups, thermal comfort was significantly higher in the tramadol versus the pethidine group >= 35 min. Blood glucose concentration in AA group increased to 135.18 +/- 9.18 mg/dL. There were some cases of nausea and vomiting in pethidine and tramadol groups but none in the AA group.Conclusion: Novamin infusion can stop postoperative shivering and alleviates hypothermia and improves thermal comfort more effectively than tramadol and pethidine with less nausea and vomiting and causes a clinically acceptable blood glucose increase with no reshivering episodes. (C) 2014 Elsevier Inc. All rights reserved.