The Effect of Central Sensitization on Postoperative Neurocognitive Dysfunction in Hospitalized Elderly Patients: A Prospective Cohort Clinical Trial.

OBJECTIVE: To investigate whether central sensitization (CS) in elderly patients was a predictive risk factor for postoperative neurocognitive dysfunction (PNCD). METHODS: One hundred and thirty-three aged patients undergoing total knee arthroplasty (TKA) who received femoral nerve block and general anesthesia were recruited in this research and prospectively assigned into two groups according to the Central Sensitization Inventory (CSI) score: group C (n = 106, CSI score less than 40) and group CS (n = 27, CSI score higher than 40). Scores of Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Confusion Assessment Method (CAM), Numerical Rating Scale (NRS) and Quality of recovery-40 (QoR-40) questionnaires were assessed. Basic information and clinical records of all participants were also collected. RESULTS: PNCD occurred in 24 (22.6%) of patients in group C and 16 (59.3%) in group CS (p < .05). Multivariate logistic regression analysis revealed that patients with CSI score ≥40 before surgery exhibited higher risk of PNCD after adjustment for other risk factors (p < .05). Compared to group C, the pre- and post-operative NRS scores, pain duration, the WOMAC score, and propofol consumptions for anesthesia induction were significantly increased in group CS (p < .05). CONCLUSION: Hospitalized elderly patients with clinical symptoms of CS scores may have increased risk of PNCD following TKA.

taVNS Alleviates Sevoflurane-Induced Cognitive Dysfunction in Aged Rats Via Activating Basal Forebrain Cholinergic Neurons.

Postoperative cognitive dysfunction (POCD) is a common complication of central nervous system after anesthesia or surgery. Sevoflurane, an inhalation anesthetic, may inhibit cholinergic pathway that induce neuronal death and neuroinflammation, ultimately leading to POCD. Transauricular vagus nerve stimulation (taVNS) has neuroprotective effects in POCD rats, but the mechanisms related to cholinergic system have not been revealed. Sprague-Dawley rats were anesthetized with sevoflurane to construct the POCD model. The immunotoxin 192-IgG-saporin (192-sap) selectively lesioned cholinergic neurons in the basal forebrain, which is the major source of cholinergic projections to hippocampus. After lesion, rats received 5 days of taVNS treatment (30 min per day) starting 24 h before anesthesia. Open field test and Morris water maze were used to test the cognitive function. In this study, rats exposed to sevoflurane exhibited cognitive impairment that was attenuated by taVNS. In addition, taVNS treatment activated cholinergic system in the basal forebrain and hippocampus, and downregulated the expression of apoptosis- and necroptosis-related proteins, such as cleaved Caspase-3 and p-MLKL, in the hippocampus. Meanwhile, the activation of Iba1+ microglial by sevoflurane was reduced by taVNS. 192-sap blocked the cholinergic system activation in the basal forebrain and hippocampus and inhibited taVNS-mediated neuroprotection and anti-inflammation effects in the hippocampus. Generally, our study indicated that taVNS might alleviate sevoflurane-induced hippocampal neuronal apoptosis, necroptosis and microglial activation though activating cholinergic system in the basal forebrain.

Necrostatin-1 Against Sevoflurane-Induced Cognitive Dysfunction Involves Activation of BDNF/TrkB Pathway and Inhibition of Necroptosis in Aged Rats.

Postoperative cognitive dysfunction (POCD) induced by anesthesia or surgery has become a common complication in the aged population. Sevoflurane, a clinical inhalation anesthetic, could stimulate calcium overload and necroptosis to POCD. In addition, necroptosis inhibitor necrostatin-1 (Nec-1) alleviated cognitive impairment caused by multiple causes, including postoperative cognitive impairment. However, whether Nec-1 exerts a neuroprotective effect on POCD via calcium and necroptosis remains unclear. We anesthetized Sprague-Dawley rats with sevoflurane to construct the POCD model and to explore the mechanism underlying neuroprotective effects of Nec-1 in POCD. Rats were treated with Nec-1 (6.25 mg/kg) 1 h prior to anesthesia. Open field test and Morris water maze were employed to detect the cognitive function. In this study, rats exposed to sevoflurane displayed cognitive dysfunction without changes in spontaneous activity; however, the sevoflurane-induced POCD could be relieved by Nec-1 pretreatment. Nec-1 decreased sevoflurane-induced calcium overload and calpain activity in the hippocampus. In addition, Nec-1 alleviated the expression of p-RIPK1, RIPK1, p-RIPK3, RIPK3, p-MLKL and MLKL. Furthermore, Nec-1 remarkably increased BDNF and p-TrkB/TrkB expression in the hippocampus of aged rats. Ultimately, our research manifests evidence that Nec-1 may play a neuroprotective role against sevoflurane-induced cognitive impairment via the increase of BDNF/TrkB and suppression of necroptosis-related pathway.

Electro-Acupuncture Pretreatment Ameliorates Anesthesia and Surgery-Induced Cognitive Dysfunction Via Inhibiting Mitochondrial Injury and nEuroapoptosis in Aged Rats.

Postoperative cognitive dysfunction (POCD) remains one of the most common complications following anesthesia and surgery (AS) in the elderly population. Calcium-mediated mitochondrial injury has been proved to induce cognitive impairment in a variety of neurologic diseases. In the current study we determined whether electro-acupuncture (EA) pretreatment ameliorated AS-induced POCD in aged rats, as well as the underlying mechanism. Eighty SD rats (18 months, male) were randomly assigned into four groups (n = 20): C, C + EA, POCD and EA + POCD. Rats in Group POCD and EA + POCD were subjected to exploratory laparotomy under sevoflurane anesthesia. Rats of Group C + EA and EA + POCD received a 5-day EA stimulation at Hegu, Neiguan and Zusanli acupoints before AS. At 3rd day after AS, open field test along with Morris water maze test were employed to examine the cognitive function of aged rats. Then hippocampal tissues were stripped and hippocampal neuronal amount, expression level of cleaved caspase-9 level, cytochrome c (Cyt C), cleaved caspase-3 level, Bcl-2, Bax, ROS expression level, apoptosis rate, mitochondrial membrane potential (MMP), cytosolic calcium concentration ([Ca2+]c), opening level of mitochondrial permeability transition pore (mPTP) and ultrastructure of hippocampal neurons were detected separately. EA pretreatment inhibited AS-induced cognitive dysfunction. Furthermore, EA pretreatment decreased level of [Ca2+]c, MMP, mPTP, ROS and hippocampal mitochondrial disruption and enhanced neuronal amount. In addition, EA pretreatment notably reduced the AS-induced increased level of cleaved caspase-9, cleaved caspase-3 and expression of Cyt c, Bax/Bcl-2 ratio, as well as neuronal apoptosis rate in aged rats. EA pretreatment ameliorates AS-induced POCD in aged rats, the potential mechanism may be associated with inhibiting calcium overload and ameliorating mitochondrial injury and neuroapoptosis in hippocampal neurons.

Effect of transcutaneous auricular vagus nerve stimulation on delayed neurocognitive recovery in elderly patients.

BACKGROUND: The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could decrease the incidence of delayed neurocognitive recovery (dNCR) in elderly adults after total joint arthroplasty (TJA). METHODS: A prospective, randomized, double-blind, sham-controlled trial was designed. In total, 124 elderly patients undergoing TJA were enrolled and randomly assigned to taVNS group (n = 62), who received taVNS at 1 h before anesthetic induction until the end of surgery, or sham stimulation (SS) group (n = 62), who received SS in the same manner. Neuropsychological batteries were performed before and at 1 week after surgery to assess the incidence of dNCR. Blood samples were collected before surgery and at 1 day after surgery to detect the activity of cholinesterase (AChE and BChE), as well as the levels of inflammatory factors (TNF-α, IL-1ß, IL-6, and HMGB1) and brain damage factor S100ß. RESULTS: Of 124 patients, 119 completed 1 week neuropsychological tests. The incidence of dNCR was significantly decreased in taVNS group [10% (6/60)] compared with the SS group [27.1% (16/59)] (P < 0.05). Patients who received taVNS had lower blood levels of AChE, BChE, IL-6, HMGB1, and S100ß after surgery (P < 0.05), as compared with those in the SS group. There was no difference in TNF-α between the two groups. CONCLUSION: The taVNS can decrease the incidence of dNCR after TJA in elderly patients, which may be related to the inhibition of inflammatory cytokine production and the reduction of cholinesterase activity.

Ultrasound-guided single popliteal sciatic nerve block is an effective postoperative analgesia strategy for calcaneal fracture: a randomized clinical trial.

OBJECTIVES: The aim of this study was to evaluate the postoperative analgesia effect of ultrasound-guided single popliteal sciatic nerve block for calcaneal fracture. METHODS: A total of 120 patients scheduled for unilateral open reduction and internal fixation of calcaneal fracture were enrolled in this prospective randomized study. Patients in group B received ultrasound-guided single popliteal sciatic nerve block after operation, but Patients in group A did not. All patients received patient-controlled intravenous analgesia (PCIA) after operation. The time to initiation of PCIA, the time of first pressing the analgesia pump, duration of analgesia pump use and the total number of times the patient pressed the analgesia pump were recorded. The time of rescue analgesia and the adverse reactions were recorded. Pain magnitude of the patients immediately after discharge from operating room (T1), and at 4th (T2), 8th (T3), 12th (T4), 16th (T5), 24th (T6) and 48th (T7) h after the operation were assessed with visual analog scale (VAS). In addition, patient, surgeon and nurse satisfaction were recorded. RESULTS: The VAS scores at T2 ~ T5, the time of rescue analgesia and the adverse reactions, the total number of times the patient pressed the analgesia pump were significantly declined in group B (p < 0.001). The time to initiation of PCIA, the time of first pressing the analgesia pump, duration of analgesia pump use were prolonged and patient surgeon and nurse satisfaction were improved in group B (p < 0.05). CONCLUSION: Ultrasound-guided single popliteal sciatic nerve block is an effective postoperative analgesia strategy for calcaneal fracture. TRIAL REGISTRATION: ChiCTR, ChiCTR2100042340. Registered 19 January 2021, URL of trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=66526 .

The Potential Role of Lung-Protective Ventilation in Preventing Postoperative Delirium in Elderly Patients Undergoing Prone Spinal Surgery: A Preliminary Study.

BACKGROUND Postoperative delirium (POD) is a frequent complication in elderly patients, usually occurring within a few days after surgery. This study investigated the effect of lung-protective ventilation (LPV) on POD in elderly patients undergoing spinal surgery and the mechanism by which LPV suppresses POD. MATERIAL AND METHODS Seventy-one patients aged ≥65 years were randomized to receive LPV or conventional mechanical ventilation (MV), consisting of intermittent positive pressure ventilation following induction of anesthesia. The tidal volume in patients who received MV was 8 ml/kg predicted body weight (PBW), and the ventilation frequency was 12 times/min. The tidal volume in patients who received LPV was 6 ml/kg PBW, the positive end-expiratory pressure was 5 cmH2O, and the ventilation frequency was 15 times/min, with a lung recruitment maneuver performed every 30 min. Blood samples were collected immediately before anesthesia induction (T0), 10 min (T1) and 60 min (T2) after turning over, immediately after the operation (T3), and 15 min after extubation (T4) for blood gas analysis. Simultaneous cerebral oxygen saturation (rSO2) and cerebral desaturation were recorded. Preoperative and postoperative serum concentrations of interleukin (IL)-6, IL-10 and glial fibrillary acidic protein (GFAP) were measured by ELISA. POD was assessed by nursing delirium screening score. RESULTS Compared with the MV group, pH was lower and PaCO2 higher in the LPV group at T2. In addition PaO2, SaO2, and PaO2/FiO2 were higher at T1, and T4, and rSO2 was higher at T3, and T4 in the LPV than in the MV group (P<0.05 each). Postoperative serum GFAP and IL-6 were lower and IL-10 higher in the LPV group. The incidences of cerebral desaturation and POD were significantly lower in the LPV group (P<0.05). CONCLUSIONS LPV may reduce POD in elderly patients undergoing spinal surgery by inhibiting inflammation and improving cerebral oxygen metabolism.

Pretreatment with nimodipine reduces incidence of POCD by decreasing calcineurin mediated hippocampal neuroapoptosis in aged rats.

BACKGROUND: Calcineurin (CaN) having a high expression in hippocampal neurons is closely related to apoptosis. Pretreatment with nimodipine can lower the apoptosis rate of hippocampal neuron to reduce the incidence of postoperative cognitive dysfunction (POCD). However, the relationship between cerebral protective effect of pretreatment with nimodipine and CaN is controversial in the literature. The aim of this study is to evaluate the relationship between neuroprotective effect of nimodipine and CaN on POCD in aged rats. METHODS: Ninety-six 18-month-old male Sprague-Dawley rats were randomly assigned into 4 groups (n = 24 each): control group (Group C), nimodipine group (Group N), surgery group (Group S) and nimodipine + surgery group (Group N + S). In Group N and Group N + S, nimodipine 1 mg/kg was intraperitoneally injected, while the equal volume of normal saline was given instead in Group S. 30 min later, Group N and Group C inhaled pure oxygen for 2 h, and Group S and N + S inhaled 3% sevoflurane for 2 h when exploratory laparotomy was performed. Morris water maze test was performed on 1 day before operation and 1, 3 and 7 days after operation. After the end of Morris water maze test at 1 day before operation and 1 and 7 days after operation, 8 rats were sacrificed, brains were removed and hippocampal tissues were obtained for detection of apoptosis in hippocampal neurons, cytoplasmic calcium ([Ca2+]i), and hippocampal CaN and caspase-3 expression. RESULTS: Compared with the 1st day before operation, the escape latency, apoptosis rate, [Ca2+]i, expression of CaN and caspase-3 increased significantly, but the frequency of crossing the original platform decreased dramatically in Group S and N + S(P<0.05). In addition, the escape latency, apoptosis rate, [Ca2+]i, and expression of CaN and caspase-3 decreased markedly, but the frequency of crossing the original platform increased significantly in Group N + S as compared with Group S (P<0.05). CONCLUSIONS: Pretreatment with nimodipine reduces the incidence of POCD by decreasing CaN mediated hippocampal neuroapoptosis in aged rats.

Decreased Endogenous Hydrogen Sulfide Generation in Penile Tissues of Diabetic Rats with Erectile Dysfunction.

INTRODUCTION: Hydrogen sulfide (H2S) is an endogenous gasotransmitter. The levels of H2S-generating enzyme expression and endogenous H2S production in diabetic rats with erectile dysfunction (ED) remain unknown. The aim of this study was to investigate the expression of the H2S-generating enzymes and endogenous production of H2S in penile tissues of diabetic ED rats. METHODS: Experimental rats were randomly divided into normal control group, apomorphine (APO)-positive group and APO-negative group. Primary rat corpus cavernosum smooth muscle cells (CCSMCs) and aortic endothelial cells (AECs) were isolated and cultured in vitro under 3 different conditions: normal glucose (NG) condition, high glucose (HG) condition, and osmotic control (OC) condition. MAIN OUTCOME MEASURES: Erectile function; H2S concentrations in plasma or penile tissues; expression of H2S-generating enzymes and endogenous H2S production in penile tissues, CCSMCs, and AECs. RESULTS: Erectile function was significantly decreasedin the APO-negative group. In addition to significantly decreased expression of cysteine aminotransferase (CAT), d-amino acid oxidase (DAO), and 3-mercaptopyruvate sulfurtransferase (3-MST), the H2S concentrations in plasma and penile tissues and endogenous H2S production were significantly decreased in the APO-negative group. Endogenous H2S production by cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) decreased to the same levels in the APO-negative and APO-positive groups as that in the normal control group. However, CBS and CSE expression remained unchanged in the 3 groups. Under HG conditions, H2S-generating enzyme expression in AECs did not change, while CAT, DAO, and 3-MST expression in CCSMCs was significantly decreased. In both cell types, H2S production by these enzymes was decreased in the HG group. CONCLUSION: Endogenous H2S production was significantly decreased in the diabetic ED rats' penile tissues due to downregulated expression of the CAT/3-MST and DAO/3-MST pathways and low activities of CBS and CSE.

Chaephilones A and B, Two New Azaphilone Derivatives Isolated from Chaetomium globosum.

Two new azaphilone derivatives, chaephilones A (1) and B (2), were isolated from the fungus Chaetomium globosum, together with four structurally related analogs 3 - 6. The structures of 1 and 2 were elucidated by comprehensive spectroscopic analyses including HR-ESI-MS and NMR. The known compounds were identified as chaetomugilin Q (3), chaetomugilin D (4), 11-epichaetomugilin A (5), and chaetomugilin S (6) by comparing their NMR data and optical rotation values with those reported. Compound 2 represents the first example of azaphilone with an open furan ring. Compounds 1 and 2 were evaluated for cytotoxic activities against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) by the MTS method.

[Effects of electroacupuncture pretreatment on long-term postoperative cognitive dysfunction and neuron-inflammation in aged rats].

OBJECTIVE: To observe the effects of electroacupuncture pretreatment on postoperative cognitive dysfunction (POCD), neuronal apoptosis and neuron-inflammation in aged rats. METHODS: Thirty-six male SD rats aged 20 months were randomly divided into sham operation group, model group and electroacupuncture (EA) group, with 12 rats in each group. The POCD rats model was prepared by internal fixation of left tibial fracture. Five days before modeling, EA stimulation (2 Hz/15 Hz, 1 mA, 30 min) was applied to "Zusanli" (ST36), "Hegu" (LI4) and "Neiguan" (PC6) on the unaffected side of rats in the EA group, once a day for consecutive 5 d. The learning and memory abilities of rats were evaluated by water maze test 31-35 days after operation. The apoptosis of hippocampal neurons was observed by Tunel/NeuN double staining. The expressions of high mobility group protein B1 (HMGB1) and phosphorylated (p)-nuclear factor (NF)-κB in microglia cells in hippocampal dentate gyrus were detected by immunofluorescence staining. The expression levels of interleukin (IL)-6 and IL-1ß in the hippocampus were detected by Western blot. RESULTS: Compared with the sham operation group, the escape latency was prolonged (P<0.05); the frequency of crossing the original platform, ratio of the swimming distance and the time in the target quadrant of the Morris water maze were significantly decreased (P<0.05); the apoptosis rate of hippocampal neurons was significantly increased (P<0.05); the expressions of HMGB1 and p-NF-κB in microglia cells in the dentate gyrus and the expression levels of IL-6 and IL-1ß in hippocampus were increased (P<0.05) in the model group. Compared with the model group, the results of the above indexes were all opposite (P<0.05) in the EA group. CONCLUSION: EA preconditioning can regulate hippocampal inflammatory response, alleviate neuronal apoptosis rate and long-term cognitive dysfunction in aged rats with POCD, the mechanisms may be related to the inhibition of microglia HMGB1/NF-κB pathway in hippocampal dentate gyrus.

Combined femoral artery block and femoral nerve block reduces thigh tourniquet-induced hypertension.

STUDY OBJECTIVE: Tourniquet hypertension (TH) is thought to be caused by sympathetically mediated C-fibers in the femoral epicardium following prolonged intraoperative inflation of the tourniquet, and we hypothesized that blocking the femoral artery at the same time as a conventional femoral nerve block would reduce the incidence of TH. DESIGN: A prospective, double-blind, randomized, controlled trial. SETTING: Operating room and hospital ward in the Third Hospital of Hebei Medical University. PATIENTS: A total of 72 patients receiving high tibial osteotomy under general anesthesia were recruited from June 2022 to September 2022. INTERVENTIONS: Patients were randomly assigned to receive either a classical femoral nerve block (CFNB) or a modified femoral nerve block (MFNB). Patients in the CFNB group received a 30 mL of 0.5% ropivacaine femoral nerve block and patients in the MFNB group received a 20 mL of 0.5% ropivacaine femoral nerve block combined with a 10 mL of 0.5% ropivacaine femoral artery block. MEASUREMENTS: The primary outcome assessed was the incidence of TH. Data on intraoperative esmolol dosage, analgesic effect, complications and hemodynamics during surgery were also recorded. MAIN RESULTS: Incidence of TH was significantly higher in the CFNB group compared with the MFNB group (71.88% vs 31.25%, P = 0.002). The systolic blood pressure in the CFNB group was significantly higher than that in the MFNB group at 45, 60, 75 and 90 min after tourniquet inflation (P = 0.029, P = 0.020, P = 0.009, P = 0.007). There was also a significant increase in intraoperative esmolol dosage in the CFNB group (65.63 ± 44.15 vs 22.19 ± 33.74, P < 0.001). Postoperative pain scores and patient satisfaction were not statistically significant between the two groups. CONCLUSIONS: The present study demonstrated that modified femoral nerve block reduced intraoperative esmolol dosage and the incidence of TH.

[Spermicidal effect of alcohol extracts from different ratios of Sophora flavescens Ait/Chinese Bulbul in vitro].

OBJECTIVE: To observe the spermicidal effect of alcohol extracts from different ratios of Sophora flavescens Ait/Chinese Bulbul in vitro. METHODS: Semen samples aseptically obtained by masturbation and prepared by density gradient centrifugation from 15 healthy men were incubated in the alcohol extracts from 9 different ratios of Sophora flavescens Ait/Chinese Bulbul for 20 seconds, 2 minutes and 4 minutes. Then the motility and movement parameters of the sperm were detected by computer-assisted semen analysis, and the minimal effective concentrations of the instant spermicidal effect of the extracts were determined. RESULTS: At the ratio of 3:1, the extract at 0.5 mg/ml significantly inhibited the sperm motility and other sperm movement parameters VCL, VSL, VAP, ALH, WOB and MAD, as compared with the control group. The minimal effective concentration of the instant spermicidal effect of the extracts was 3.5 mg/ml at 3:1. CONCLUSION: The alcohol extracts from Sophora flavescens Ait and Chinese Bulbul at the ratio of 3:1 have the best spermicidal effect in vitro.

TLR3 deletion inhibits programmed necrosis of brain cells in neonatal mice with sevoflurane-induced cognitive dysfunction.

This research aimed to explore the influence of TLR deletion on sevoflurane-induced postoperative cognitive dysfunction in neonatal mice. Herein, WT and TLR3 KO neonatal mice, each with 24, were randomly divided into control group, sevoflurane group, and TLR3-/-+sevoflurane group. The hippocampal neurons of WT, TLR3 KO and RIP3 KO neonatal mice in C group, SEV group, TLR3-/-+SEV group and RIP3-/-+SEV group were extracted for in vitro experiments. The results revealed the degeneration and necrosis of nerve cells in SEV group. Microscopic findings indicated that nerve cells showed shrinkage and nuclear hyperchromatism, along with lessening or even disappearance of nuclei and enlargement of cell spaces, and apoptotic cells in the brain tissues were evidently increased. Compared with SEV group, TLR3-/-+SEV group displayed reductions in these phenomena. Additionally, SEV group showed the reduced SHP2 expression and the increased expressions of proteins associated with TLR signaling pathway and apoptosis. Furthermore, there were no obvious differences in the expressions of such proteins in hippocampal neurons between RIP3-/-+SEV and TLR3-/-+SEV groups. The results confirmed that inhibiting RIP3 phosphorylation and suppressing TLR3 expressions exerted the same influence on the expressions of these proteins in the hippocampus of neonatal mice with sevoflurane-induced cognitive dysfunction. Based on these, it is speculated that TLR3 influences neonatal mice with sevoflurane-induced cognitive dysfunction probably by regulating RIP3 phosphorylation.

Effect of Transauricular Vagus Nerve Stimulation on Rebound Pain After Ropivacaine Single Injection Femoral Nerve Block for Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial.

Purpose: The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could reduce the incidence of rebound pain in patients undergoing anterior cruciate ligament reconstruction (ACLR) under general anesthesia combined with preoperative femoral nerve block. Methods: In total, 78 patients were enrolled in this prospective, randomized, double-blind, and sham-controlled study. Patients were randomly assigned to 2 groups (n=39): Group taVNS received taVNS (1h /1time, 6times) within the first 12 h after surgery; Group SS received sham stimulation (SS) in the same manner. Pain scores at 0, 4, 8, 12, 24, 48 h after surgery were assessed with Numeric Pain Rating Scale (NRS). The incidence, duration and onset of rebound pain were recorded. In addition, additional analgesic requirements and side effects in the first 48 h postoperatively, as well as sleep disturbance on the night of surgery, were examined. Results: The incidence and duration of rebound pain were lower in the taVNS group than in the SS group (P=0.025 and P=0.015, respectively). Pain scores at 8 h and 12 h postoperatively were significantly lower in the taVNS group compared with the SS group (P<0.05). The number of times to press the patient-controlled analgesia (PCA) pump and the number of patients requiring additional analgesic were significantly lower in the taVNS group than in the SS group until 12 h after surgery (P=0.021 and P=0.004, respectively). The number of patients with sleep disturbance in the taVNS group was lower than that in the SS group (P=0.030). Conclusion: The taVNS exerts beneficial effect on rebound pain after femoral nerve block in patients undergoing ACLR, which reduces the incidence and duration of rebound pain, the need for postoperative additional analgesic, and the number of complications.

Young plasma reverses anesthesia and surgery-induced cognitive impairment in aged rats by modulating hippocampal synaptic plasticity.

We investigated the protective effect of young plasma on anesthesia- and surgery-induced cognitive impairment and the potential underlying mechanism using bioinformatics, functional enrichment analysis, gene set enrichment analysis, Golgi-Cox staining, dendritic spine analysis, immunofluorescence assay, western blot analysis, and transmission electron microscopy. Furthermore, we performed behavioral assessments using the open field test, the novel object recognition test, and the Morris water maze test. We identified 1969 differentially expressed genes induced by young plasma treatment, including 800 upregulated genes and 1169 downregulated genes, highlighting several enriched biological processes (signal release from synapse, postsynaptic density and neuron to neuron synapse). Anesthesia- and surgery-induced cognitive impairment in aged rats was comparatively less severe following young plasma preinfusion. In addition, the decreased levels of synapse-related and tyrosine kinase B/extracellular signal-regulated protein kinase/cyclic adenosine monophosphate response element-binding protein (TrkB/ERK/CREB) signaling pathway-related proteins, dendritic and spine deficits, and ultrastructural changes were ameliorated in aged mice following young plasma preinfusion. Together, these findings suggest that young plasma reverses anesthesia- and surgery-induced cognitive impairment in aged rats and that the mechanism is associated with the activation of the TrkB/ERK/CREB signaling pathway and improvement in hippocampal synaptic plasticity.

Sevoflurane exposure causes neuronal apoptosis and cognitive dysfunction by inducing ER stress via activation of the inositol 1, 4, 5-trisphosphate receptor.

The role of the inositol 1, 4, 5-trisphosphate receptor (IP3R) in hippocampal neuronal apoptosis and cognitive dysfunction induced by sevoflurane is currently unclear. Therefore, in this study, we investigated the role of the IP3R in endoplasmic reticulum (ER) stress and hippocampal neuronal apoptosis induced by sevoflurane in aged rats and isolated hippocampal neurons using both in vivo and in vitro experiments, including bioinformatics, functional enrichment analysis, gene set enrichment analysis, hematoxylin, and eosin staining, TUNEL assay, flow cytometry, western blot analysis and transmission electron microscopy. Furthermore, behavioral assessment was performed with the Morris water maze test. We identified 232 differentially expressed genes induced by sevoflurane exposure, including 126 upregulated genes and 106 downregulated genes. Sevoflurane exposure caused cognitive impairment and neuronal injury, and increased p-IP3R levels and ER stress. An IP3R inhibitor, 2-APB, suppressed these changes, while an IP3R agonist, FK-506, aggravated these changes. Together, these findings suggest that sevoflurane exposure causes marked cognitive dysfunction in aged rats and neuronal injury in isolated hippocampal neurons by activating the IP3R and inducing cytoplasmic calcium overload, thereby resulting in ER stress and hippocampal neuronal apoptosis. GRAPHICAL ABSTRACT.

Activation of astrocyte Gq pathway in hippocampal CA1 region attenuates anesthesia/surgery induced cognitive dysfunction in aged mice.

The elderly are particularly vulnerable to brain dysfunction after fracture surgery, but the mechanism underlying the cognitive decline due to anesthesia/surgery is not well understood. In this study, we observed hippocampus-dependent cognitive impairment in aged mice undergoing anesthesia and tibial fracture surgery, a common model of postoperative cognitive dysfunction in aged mice. We used Golgi staining and neuroelectrophysiological techniques to detect structurally and functionally impaired synaptic plasticity in hippocampal CA1 region of Postoperative cognitive dysfunction aged mice, respectively. Based on the 'third party synapse' hypothesis of astrocytes, we used glial fibrillary acidic protein to label astrocytes and found an increase in abnormal activation of astrocytes in the CA1 region of hippocampus. We hypothesize that abnormal astrocyte function is the driving force for impaired synaptic plasticity. So we used chemogenetic methods to intervene astrocytes. Injection of adeno-associated virus into the CA1 region of the hippocampus bilateral to aged mice resulted in the specific expression of the Gq receptor, a receptor specially designed to be activated only by certain drugs, within astrocytes. The results of novel object recognition and conditioned fear experiments showed that CNO activation of astrocyte Gq pathway could improve the learning and memory ability and the synaptic plasticity of Postoperative cognitive dysfunction aged mice was also improved. The results of this study suggest that activation of the Gq pathway in astrocytes alleviates Postoperative cognitive dysfunction induced by anesthesia and surgery in aged mice.

IL-17A deletion reduces sevoflurane-induced neurocognitive impairment in neonatal mice by inhibiting NF-κB signaling pathway.

We investigated the role of IL-17A in sevoflurane-inducedneurocognitive impairment in neonatal mice. Seventy-two wild-type (WT) and 42 IL-17A knockout (KO) neonatal mice were randomly divided into WT (n = 36), IL-17A-/- (n = 6), sevoflurane (Sev, n = 36), and IL-17A-/- + sevoflurane (IL-17A-/- + Sev, n = 36) groups. The latter two groups were given 3% sevoflurane for 2 h per day on postnatal days (P) 6-8. Behavioral experiments were performed on P30-36. At P37, RNA sequencing and qRT-PCR of the hippocampus was performed, neurons were detected by Nissl staining, and neuropathological changes were evaluated by HE staining. NF-κB pathway-related proteins were evaluated by western blot and immunofluorescence analyses, IL-1ß and IL-6 levels were assessed by ELISA. RNA sequencing identified 131 differentially expressed genes, highlighting several enriched biological processes (chemokine activity, immune response, extracellular region, extracellular space, inflammatory response) and signaling pathways (IL-17 signaling pathway, chemokine signaling pathway, cytokine-cytokine receptor interaction, ECM-receptor interaction and influenza A). Repeated sevoflurane exposures induced long-term cognitive impairment in WT mice. The cognitive impairment was comparatively less severe in IL-17A KO mice. In addition, the increased levels of NF-κB p65, iNOS, COX-2, IL-17A, IL-6 and IL-1ß, reduced neuronal numbers and neuropathological changes were ameliorated in neonatal mice in the IL-17A-/- + Sev group compared with neonatal mice in Sev group. IL-17A deletion protects against long-term cognitive impairment induced by repeated sevoflurane exposure in neonatal mice. The underlying mechanism may relate to inhibiting NF-κB signaling pathway as well as the reducing neuroinflammation.

Median Effective Concentration of Ropivacaine for Femoral Nerve Block Maintaining Motor Function During Knee Arthroscopy in Two Age Groups.

Background: Femoral nerve block combined with general anesthesia is commonly used for patients undergoing knee arthroscopy in ambulatory care centers. An ideal analgesic agent would selectively (differentially) block sensory fibers, with little or no effect on motor nerves. Ropivacaine is considered to cause less motor block than others. This study investigated the median effective concentration (EC50) of ropivacaine for differential femoral nerve block in adults either younger or older than 60 years. Methods: Patients with American Society of Anesthesiologists physical status I-III and scheduled for knee arthroscopy were categorized as 18- to 60-years-old (Group 1), or older than 60 years (Group 2). Surgeries were performed under general anesthesia combined with femoral nerve block via 22 mL ropivacaine. The EC50 of ropivacaine for differential femoral nerve block was determined using the up-and-down method and probit regression. The primary outcome was the EC50 (95% confidence interval [CI]) of the 2 groups. Data on the sensory block, analgesic effect, complications, and hemodynamics during surgery were also recorded. Results: The EC50 of 22 mL ropivacaine for differential femoral nerve block of Group 1 (0.124%, 95% CI 0.097-0.143%) was significantly higher than that of Group 2 (0.088%, 95% CI 0.076-0.103%). The sensory block and hemodynamic data of the 2 groups were comparable. None of the patients experienced neurological complications. Conclusion: The EC50 of ropivacaine administered for differential femoral nerve block during knee arthroscopy was lower in patients older than 60 years, relative to younger adults.