Chronic Neuropathic Pain and Comorbid Depression Syndrome: From Neural Circuit Mechanisms to Treatment.

Chronic neuropathic pain and comorbid depression syndrome (CDS) is a major worldwide health problem that affects the quality of life of patients and imposes a tremendous socioeconomic burden. More than half of patients with chronic neuropathic pain also suffer from moderate or severe depression. Due to the complex pathogenesis of CDS, there are no effective therapeutic drugs available. The lack of research on the neural circuit mechanisms of CDS limits the development of treatments. The purpose of this article is to provide an overview of the various circuits involved in CDS. Notably, activating some neural circuits can alleviate pain and/or depression, while activating other circuits can exacerbate these conditions. Moreover, we discuss current and emerging pharmacotherapies for CDS, such as ketamine. Understanding the circuit mechanisms of CDS may provide clues for the development of novel drug treatments for improved CDS management.

Evaluating the efficacy and safety of perianal injection of liposomal ropivacaine HR18034 for postoperative analgesia following hemorrhoidectomy: A multicenter, randomized, double-blind, controlled phase II clinical trial.

STUDY OBJECTIVE: HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free ropivacaine, has performed well in animal experiments and phase I clinical trials. This trial was to investigate the efficacy, safety, pharmacokinetic profile and the minimum effective dose of HR18034 for postoperative analgesia after hemorrhoidectomy compared with ropivacaine. DESIGN: A multicenter, randomized, double-blind trial. SETTING: 19 medical centers in China. PATIENTS: 85 patients undergoing hemorrhoidectomy between October 2022 to November 2022. INTERVENTIONS: Patients were randomly divided into HR 18034 190 mg group, 285 mg group, 380 mg group and ropivacaine 75 mg group, receiving single local anesthetic perianal injection for postoperative analgesia. MEASUREMENTS: The primary outcome was the area under the resting state NRS score -time curve within 72 h after injection. The second outcomes included the proportion of patients without pain, the proportion of patients not requiring rescue analgesia, cumulative morphine consumption for rescue analgesia, etc. Safety was evaluated by adverse events incidence and plasma ropivacaine concentrations were measured to explore the pharmacokinetic characteristics of HR18034. MAIN RESULTS: The areas under the NRS score (at rest and moving states)-time curve were significantly lower in HR 18034 380 mg group than ropivacaine 75 mg at 24 h, 48 h, and 72 h after administration. However, this superiority was not observed in HR18034 190 mg group and 285 mg group. There was no difference in cumulative morphine consumption for rescue analgesia between HR 18034 groups and ropivacaine group. CONCLUSIONS: HR 18034 380 mg showed superior analgesic efficacy and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose.

Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice.

BACKGROUND: Psilocybin offers new hope for treating mood disorders due to its rapid and sustained antidepressant effects, as standard medications require weeks or months to exert their effects. However, the mechanisms underlying this action of psilocybin have not been identified. AIMS: To investigate whether psilocybin has rapid and sustained antidepressant-like effects in mice and investigate whether its potential mechanisms of action are related to promoted neuroplasticity. METHODS: We first examined the antidepressant-like effects of psilocybin in normal mice by the forced swimming test and in chronic corticosterone (CORT)-exposed mice by the sucrose preference test and novelty-suppressed feeding test. Furthermore, to explore the role of neuroplasticity in mediating the antidepressant-like effects of psilocybin, we measured structural neuroplasticity and neuroplasticity-associated protein levels in the prefrontal cortex (PFC) and hippocampus. RESULTS: We observed that a single dose of psilocybin had rapid and sustained antidepressant-like effects in both healthy mice and chronic CORT-exposed mice. Moreover, psilocybin ameliorated chronic CORT exposure-induced inhibition of neuroplasticity in the PFC and hippocampus, including by increasing neuroplasticity (total number of dendritic branches and dendritic spine density), synaptic protein (p-GluA1, PSD95 and synapsin-1) levels, BDNF-mTOR signalling pathway activation (BDNF, TrkB and mTOR levels), and promoting neurogenesis (number of DCX-positive cells). CONCLUSIONS: Our results demonstrate that psilocybin elicits robust, rapid and sustained antidepressant-like effects which is accompanied by the promotion of neuroplasticity in the PFC and hippocampus.

The protective effect of vitamin A palmitate eye gel on the ocular surface during general anaesthesia surgery: a randomized controlled trial.

PURPOSE: To investigate the change in tear production associated with general anesthesia and the protective effect of vitamin A palmitate eye gel on the ocular surface during general anesthesia. METHODS: This double-blind, randomized clinical trial included patients undergoing non-ophthalmic surgery under general anesthesia who randomly received vitamin A palmitate eye gel and taping for one eye (Group A, n = 60) or taping alone for the other eye (Group B, n = 60). Symptom assessment in dry eye (SANDE) score, tear film break-up time (TBUT), corneal fluorescein staining (CFS) score, and Schirmer tear test I (STT-1) were analyzed under a hand-held slit lamp before anesthesia (T0), 0.5 h postoperatively (T1), and 24 h postoperatively (T2). RESULTS: At 0.5 h postoperatively, an increase in CFS score was observed in both groups (P < 0.05 in Group A and P < 0.01 in Group B), and the participants in Group A had less corneal abrasions than those in Group B. STT-1 significantly increased in Group A (P < 0.05), while it significantly decreased in Group B (P < 0.001). The changes between the two groups were statistically significant (P < 0.001). At 24 h postoperatively, both CFS score and STT-1 almost returned to baseline levels in the two groups. In both groups, the SANDE score and TBUT showed little change at 0.5 h and 24 h postoperatively (all P > 0.05). CONCLUSION: Vitamin A palmitate eye gel effectively protected the ocular surface and aqueous supplementation during general anesthesia. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100052140) on 20/10/2021.

Intravenous injection of dexamethasone is non-inferior to perineural administration for popliteal sciatic nerve and saphenous nerve blocks: A randomized, controlled, triple-blind study.

Background: The aim of this study was to assess whether intravenous dexamethasone was noninferior to perineural dexamethasone as an adjuvant to ropivacaine for a combination of saphenous and sciatic nerve blocks in patients undergoing foot and ankle surgery. Methods: This was a prospective, blinded, randomized noninferiority study. Seventy-five patients, aged 18-75 years, with an American Society of Anesthesiologists (ASA) physical status I-III who underwent foot and ankle surgery were involved. Patients scheduled for ultrasound-guided popliteal sciatic nerve block and saphenous nerve block were randomized to receive 0.375% ropivacaine with 7.5 mg of dexamethasone perineurally (Dex-PN), 10 mg of dexamethasone intravenously (Dex-IV) or neither (Placebo). The primary outcome was the duration of analgesia. The major secondary outcomes were the composite pain intensity and opioid consumption score at 0-48 h intervals after anesthesia. Results: The mean analgesic duration was 26.2 h in the Dex-IV group and 27.9 h in the Dex-PN group (duration difference, -1.7; 95% CI, -3.8 to 0.43; P = 0.117), and both durations were significantly longer than that in the placebo group (17.6 h, P < 0.001). Conditions for establishing non-inferiority were met. Conclusions: Our findings indicate that a single 10-mg intravenous dose of dexamethasone was noninferior to the combined dose of ropivacaine plus deaxmethasone in terms of duration of analgesia for foot and ankle surgery.

Effect of Aggressive Warming versus Routine Thermal Management on the Incidence of Perioperative Hypothermia in Patients Undergoing Thyroid Surgery: A Prospective, Randomized, Double-Blind Controlled Trial.

Purpose: Despite the implementation of various insulation measures, the incidence of hypothermia during thyroid surgery remains high. This randomized controlled study aimed to evaluate the effects of aggressive thermal management combined with resistive heating mattresses to prevent perioperative hypothermia in patients undergoing thyroid surgery. Patients and Methods: 142 consecutive patients scheduled for elective thyroid surgery were enrolled in the study. They were randomly and equally allocated to the aggressive warming or routine care groups (n = 71). The patients' body temperature was monitored before the induction of anesthesia until they returned to the ward. The primary outcome was the incidence of perioperative hypothermia. Secondary outcomes included postoperative complications, such as mortality, cardiovascular complications, wound infection, shivering, postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, fever, headache and hospital length of stay (LOS). Results: In our study, the results showed that a significantly higher rate of hypothermia was observed in the routine care group compared with the aggressive warming group. The incidence of perioperative hypothermia was 19.72% (14/71) in the aggressive warming group and 35.21% (25/71) in the routine care group (P < 0.05). The incidence of shivering in the aggressive warming group (1.41%) was significantly lower than that in the routine care group (11.27%) (P < 0.05), and a one-day reduction in hospital length of stay was observed in the aggressive warming group (P < 0.05). There was no significant difference in mortality or other postoperative complications, such as cardiovascular complications, wound infection, PONV, pain, fever or headache, between the two groups (P > 0.05). Conclusion: Our results suggest that aggressive thermal management combined with resistive heating mattresses provided improved perioperative body temperature and reduced the incidence of perioperative hypothermia and shivering compared to routine thermal management.

●The incidence of perioperative hypothermia during thyroid surgery was high. ●The use of resistive heating mattresses during thyroid surgery can effectively reduce the occurrence of perioperative hypothermia. ●It is recommended to take aggressive thermal protection during the operation of minor and medium surgeries, and to continuously monitor the temperature.

Comparison of diffusion ranges at different local anesthetic volumes during superior laryngeal nerve block.

OBJECTIVES: Ultrasound-guided superior laryngeal nerve (SLN) block is a practical and painless approach to avoid the hemodynamic stress response during endotracheal intubation and relieve sore throat after laryngeal surgery. The main purpose of this study was to establish an optimal dosage of local anesthetic when performing SLN block to help anesthetists balance analgesia and side effects. METHODS: Twenty fresh larynx specimens were obtained immediately after resection and then injected with 2-, 3-, 4-, or 5- mL of a lidocaine-blue dye mixture at bilateral SLN puncture sites. Superficial areas of deposited blue dye were measured. Dye leakage and surrounding dyed tissue were recorded. Another 40 patients were included in the ultrasound investigation. Distances between the internal branch of the SLN (iSLN) and adjacent structures were calculated. RESULTS: The dye spread area was greater with the administration of larger doses, especially to the visceral space. A 2- or 3-mL injection of local anesthetic was sufficient to infiltrate the SLN gap. A higher incidence of dye leaking out of the thyrohyoid membrane and anterior epiglottis space was observed; furthermore, there was substantially more dyed hyoid/thyroid cartilage with 4 and 5 mL of injected dye mixture than 2 mL. There was no significant difference between the specimen and ultrasound measurements of for length of iSLN-adjacent structures. CONCLUSIONS: In the Chinese population, 2- or 3- mL of local anesthetic is a safe dose during SLN block. A larger volume could overflow from the cavity to cause complications. The thyrohyoid membrane combined with the superior laryngeal artery is a reliable target for positioning the iSLN during ultrasound-guided regional anesthesia.

The Use of Preoperative Video Distraction on Emergence Delirium in Preschool Children Undergoing Strabismus Surgery Under Anesthesia with Sevoflurane: A Randomized Controlled Trial.

Purpose: The aim of this study was to determine whether preoperative video distraction reduces the incidence of emergence delirium in preschool children under general anesthesia with sevoflurane. Patients and Methods: In this prospective randomized controlled study, children aged 3-6 years were randomized to receive either video distraction (Group V) or common clinical practice (Group C) from arrival at the holding area to induction of anesthesia. The primary outcome was the incidence of emergence delirium. Preoperative anxiety scores, assessed by the simple modified Yale Perioperative Anxiety Scale, were also collected. Results: A total of 160 patients were included in our study. The children in Group V (n=80) exhibited a significantly lower incidence of emergence delirium than did those in Group C (n=80) (12.5% vs 35.0%; RR 0.36, 95% CI 0.19, 0.69; P =0.0008). The maximum Pediatric Anesthesia Emergence Delirium score in Group V was significantly lower than that in Group C (3.0 vs 5.0; mean difference -2.64, 95% CI: -4.12, -1.16; P=0.0003). The simple modified Yale Perioperative Anxiety Scale scores at separation from parents and the onset of inhalation induction in Group V were significantly lower than those in Group C (36.4 ± 9.9 vs 48.2 ± 16.7; mean difference 11.92, 95% CI 7.25, 16.59; P<0.0001 and 41.5 ± 15.9 vs 59.7 ± 21.5; mean difference 18.11, 95% CI 11.76, 24.47; P<0.0001). Conclusion: Preoperative video distraction reduces the incidence of emergence delirium in preschool children who undergo strabismus surgery under general anesthesia with sevoflurane.

Protection of Ndrg2 deficiency on renal ischemia-reperfusion injury via activating PINK1/Parkin-mediated mitophagy.

BACKGROUND: Renal ischemia-reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N-myc downstream-regulated gene 2 (Ndrg2) in R-I/R injury. METHODS: We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient (Ndrg2-/-) mice and wild type (Ndrg2+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion injury (OGD-R) in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2+/+ and Ndrg2-/- mice after R-I/R injury or HK-2 cells in OGD-R injury. RESULTS: We found that Ndrg2 was primarily expressed in renal proximal tubules and significantly decreased its expression 24 h after R-I/R injury. Ndrg2-/- mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway. CONCLUSION: Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.

Effect of maternal oxygen supplementation for parturient undergoing elective cesarean section by high-flow nasal oxygen compared with room air on fetal acidemia: study protocol for a randomized controlled trial.

BACKGROUND: Maternal oxygen supplementation is usually used as an intrauterine resuscitation technique to prevent fetal hypoxia and acidemia during delivery. However, there has been a great deal of controversy regarding the effects of prophylactic maternal oxygen during cesarean section, during which the incidence of fetal acidemia seems to be higher compared with that during labor. High-flow nasal oxygen (HFNO) can improve oxygenation better in patients with high-flow oxygen airflow. The purpose of this study is to determine whether maternal oxygen supplementation with HFNO has a positive effect on fetal acidemia during cesarean section through umbilical arterial blood gas analysis. METHOD: This prospective, single-center, randomized, double-blinded trial will enroll 120 patients undergoing cesarean section. Participants will be randomly assigned to the HFNO group or air group at a 1:1 ratio. For parturients in the HFNO group, the flow rate is 40L/min, and the oxygen is heated to 37℃ with humidity 100% oxygen concentration through the Optiflow high-flow nasal oxygen system. And for the air group, the flow rate is 2 L/min with an air pattern through the same device. The primary outcome was umbilical artery (UA) lactate. Secondary outcomes include UA pH, PO2, PCO2, BE, the incidence of pH < 7.20 and pH < 7.10, Apgar scores at 1 and 5 min, and neonatal adverse outcomes. DISCUSSION: Our study is the first trial investigating whether maternal oxygen supplementation with HFNO can reduce the umbilical artery lactate levels and the incidence of fetal acidemia in cesarean section under combined spinal-epidural anesthesia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05921955. Registered on 27 June 2023.

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

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

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation.

Sepsis is an unusual systemic reaction with high mortality and secondary septic liver injury is proposed to be the major cause of mortality. Extracorporeal membrane oxygenation (ECMO) can enhance terminal organ perfusion by elevating circulatory support which is used in severe sepsis patients. However, the interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response. Besides, inflammation and apoptosis are the main mediators in the pathophysiology of septic liver injury. Therefore, we investigated the protective effect of Deoxyribonuclease I (DNase I) against septic liver injury supported by ECMO in rats. Sepsis was induced by lipopolysaccharide (LPS) and 24 hours after the administration, the rats were treated with ECMO. Then blood samples and liver tissues were collected. DNase I significantly attenuated the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and significantly decreased hepatic levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, myeloperoxidase (MPO), downstream inflammatory factor interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), and improved neutrophil infiltration. Additionally, DNase I significantly reduced the expression of apoptosis key protein and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-labeled apoptotic hepatocytes. In summary, our findings demonstrated that DNase I alleviates liver injury in ECMO-supported septic rats by reducing the inflammatory and apoptotic responses.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange Augments Oxygenation in Children With Juvenile Onset Recurrent Respiratory Papillomatosis During Surgery: A Prospective Randomized Crossover Controlled Trial.

BACKGROUND: Evidence is lacking regarding the efficacy of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) in tubeless anesthesia, especially in pediatric patients. This study aimed to evaluate the use of THRIVE for juvenile onset recurrent respiratory papillomatosis (JORRP) patients. METHODS: Twenty-eight children aged 2 to 12 years with JORRP, abnormal airways, and ASA physical status II-III that presented for surgical treatment under general anesthesia were included in this study. Each patient received 2 interventions in random order, with a 5-minute washout period between treatments: apnea without oxygen supplementation and apnea with THRIVE intervention. The primary outcome apnea time was defined as the duration from withdrawal of intubation to reintubation and resumption of controlled ventilation. The secondary outcomes were the mean transcutaneous carbon dioxide (tc co2 ) increase rate, the minimum pulse oxygen saturation (Sp o2 ) during apnea, and the occurrence of unexpected adverse effects. RESULTS: The median apnea time in the THRIVE period was significantly longer than that in the control period (8.9 [8.6-9.4] vs 3.8 [3.4-4.3] minutes; mean difference [95% confidence interval (CI)], 5.0 [4.4-5.6]; P < .001) for all patients. The rate of CO 2 change in the control period was higher than that in the THRIVE period both for patients aged 2 to 5 years old (6.29 [5.19-7.4] vs 3.22 [2.92-3.76] mm Hg min -1 ; mean difference [95% CI], 3.09 [2.27-3.67]; P < .001) and for patients aged 6 to 12 years old (4.76 [3.7-6.2] vs 3.38 [2.64-4.0] mm Hg min -1 ; mean difference [95% CI], 1.63 [0.75-2.56]; P < .001). The minimum Sp o2 was significantly higher in the THRIVE period than in the control period (mean difference [95% CI], 19.7 [14.8-22.6]; P < .001). CONCLUSIONS: Our findings demonstrate that THRIVE safely increased the apnea time among children with JORRP undergoing surgery and decreased the rate of carbon dioxide increase. THRIVE is clinically recommended as an airway management technique for tubeless anesthesia in apneic children.

Prognostic Nutritional Index (PNI) as a potential predictor and intervention target for perioperative ischemic stroke: a retrospective cohort study.

BACKGROUND: The prognostic nutritional index (PNI) is a nutritional indicator and predictor of various diseases. However it is unclear whether PNI can be a predictor of perioperative ischemic stroke. This study aims to evaluate the association of the preoperative PNI and ischemic stroke in patients undergoing non-cardiac surgery. METHODS: The retrospective cohort study included patients who underwent noncardiac surgery between January 2008 and August 2019. The patients were divided into PNI ≥ 38.8 and PNI < 38.8 groups according to the cut-off value of PNI. Univariate and multivariate logistic regression analyses were performed to explore the association between PNI and perioperative ischemic stroke. Subsequently, propensity score matching (PSM) analysis was performed to eliminate the confounding factors of covariates and further validate the results. Subgroup analyses were completed to assess the predictive utility of PNI for perioperative ischemic stroke in different groups. RESULTS: Amongst 221,542 hospitalized patients enrolled, 485 (0.22%) experienced an ischemic stroke within 30 days of the surgery, 22.1% of patients were malnourished according to PNI < 38.8, and the occurrence of perioperative ischemic stroke was 0.34% (169/49055) in the PNI < 38.8 group. PNI < 38.8 was significantly associated with an increased incidence of perioperative ischemic stroke whether in univariate logistic regression analysis (OR = 1.884, 95% CI: 1.559-2.267, P < 0.001) or multivariate logistic regression analysis (OR = 1.306, 95% CI: 1.061-1.602, P = 0.011). After PSM analysis, the ORs of PNI < 38.8 group were 1.250 (95% CI: 1.000-1.556, P = 0.050) and 1.357 (95% CI: 1.077-1.704, P = 0.009) in univariate logistic regression analysis and multivariate logistic regression analysis respectively. The subgroup analysis indicated that reduced PNI was significantly associated to an increased risk of perioperative ischemic stroke in patients over 65 years old, ASA II, not taking aspirin before surgery, without a history of stroke, who had neurosurgery, non-emergency surgery, and were admitted to ICU after surgery. CONCLUSIONS: Our study indicates that low preoperative PNI is significantly associated with a higher incidence of ischemic stroke in patients undergoing non-cardiac surgery. Preoperative PNI, as a preoperative nutritional status evaluation index, is an independent risk factor useful to predict perioperative ischemic stroke risk, which could be used as an intervenable preoperative clinical biochemical index to reduce the incidence of perioperative ischemic stroke.

A Prospective Randomized Study for the Placement of Flexible Laryngeal Airway Mask with Two-Step of Jaw-Thrust Technique by Both Hands for Adults.

To investigate the effect of two-step of jaw-thrust technique on the placement of flexible laryngeal mask with both hands. 157 patients scheduled for functional endoscopic sinus surgery were divided into two groups using a random number table method: control group (group C, n = 78) and test group (group T, n = 79). After induction of general anesthesia, the traditional method was applied to insert the flexible laryngeal airway mask in group C, and the two-step of jaw-thrust technique with both hands by the nurse was applied to help place the laryngeal mask in group T. The success rate, alignment status, oropharyngeal leak pressure (OLP) of the laryngeal mask, soft tissue injury of the oropharyngeal cavity and postoperative sore throat, and the incidence of adverse airway event were recorded in both groups. Results: The success rate of the first placement of flexible laryngeal masks in group C and group T were 73.8% and 97.5%, and the final success rates were 97.5% and 98.7%, respectively. Compared with group C, the success rate of first placement in group T was higher, and the difference was statistically significant (P < 0.01). There was no significant difference in the final success rate between the two groups (P = 0.56). The alignment score showed that the placement of group T was better than that of group C, and the difference was statistically significant (P < 0.01). The OLP of group C was 22.1 ± 2.6 cmH2O, and the OLP of group T was 25.4 ± 3.8 cmH2O. The OLP of group T was significantly higher than that of group C (P < 0.01). The incidence of mucosal injury and postoperative sore throat in group T were 2.5% and 5.0%, which were significantly lower than that of 23.0% and 16.7% in group C (both P < 0.01). There was no adverse airway event in each group. Conclusion: The two-step of jaw-thrust technique with both hands can improve the success rate of the first placement of the flexible laryngeal mask and the positioning of the laryngeal mask, increase the sealing pressure of the laryngeal mask, and reduce the incidence of oropharyngeal soft tissue injury and postoperative pharyngeal pain.

Psilocybin facilitates fear extinction in mice by promoting hippocampal neuroplasticity.

BACKGROUND: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. METHODS: First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. RESULTS: A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. CONCLUSIONS: A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.

Inhalational Anesthesia is Noninferior to Total Intravenous Anesthesia in Terms of Surgical Field Visibility in Endoscopic Sinus Surgery: A Randomized, Double-Blind Study.

Purpose: Regarding the quality of surgical field visibility, previous studies and meta-analyses comparing total intravenous anesthesia (TIVA) and inhalational anesthesia (IA) in endoscopic sinus surgery (ESS) have presented inconsistent findings. Considering that IA has some advantages over TIVA, we aimed to test the hypothesis that IA with sevoflurane-remifentanil is noninferior to TIVA with propofol-remifentanil in terms of surgical field visibility quality during ESS. Patients and Methods: In this randomized, double-blind, noninferiority clinical trial, 110 adult patients were recruited and randomly assigned to the IA (n = 55) or TIVA (n = 55) group. The primary outcome was the quality of surgical field visibility, as measured by the intraoperative mean Boezaart score (BS). Additionally, post hoc analysis was performed for patients with Lund-Mackay scores of ≤ 12 or > 12. Other secondary outcomes included total blood loss, bleeding rate, total fluid, mean arterial pressure, heart rate, dose of remifentanil for anesthesia maintenance, end-tidal CO2, length of stay in the post anesthesia care unit, postoperative hypoxemia, sore throat, and nausea. Results: The intraoperative mean BS of the IA group was noninferior to that of the TIVA group [medians with interquartile ranges (IQRs), 2.0 (1.7-2.2) vs 2.0 (1.8-2.1), P = 0.923]. Moreover, post hoc analysis confirmed no difference between IA and TIVA for patients with Lund-Mackay scores ≤ 12 (P = 0.403) or > 12 (P = 0.226). No differences in total blood loss, bleeding rate, or other intraoperative indicators or complications were observed between groups. Conclusion: Regarding surgical field visibility during ESS, IA with sevoflurane-remifentanil is noninferior to TIVA with propofol-remifentanil anesthesia maintenance.

Thoracic Paravertebral Block Decreased Body Temperature in Thoracoscopic Lobectomy Patients: A Randomized Controlled Trial.

Purpose: Thoracic paravertebral block (TPVB) may be highly beneficial for thoracoscopic lobectomy patients, but it may increase the risk of hypothermia. Apart from its anesthetic-reducing effects, this randomized controlled trial aimed to investigate the hypothermic effect of TPVB, and thus optimize its clinical use. Patients and methods: Adult patients were randomly allocated to two groups: TPVB + general anesthesia (GA) group or GA group. In the TPVB+GA group, the block was performed after GA induction by an experienced but unrelated anesthesiologist. Both the lower esophageal and axillary temperature were recorded at the beginning of surgery (T0) and every 15 min thereafter (T1-T8), and the end of surgery (Tp). The primary outcome was the lower esophageal temperature at Tp. The secondary outcomes included lower esophageal temperature from T0-T8 and axillary temperature from T0-Tp. The total propofol, analgesics, and norepinephrine consumption and the incidence of adverse events were also recorded. Results: Forty-eight patients were randomly allocated to the TPVB+GA (n=24) and GA (n=24) groups. The core temperature at the end of the surgery was lower in the TPVB+GA group than the GA group (35.90±0.30°C vs 36.35±0.33°C, P<0.001), with a significant difference from 45 min after the surgery began until the end of the surgery (P<0.05). In contrast, the peripheral temperature showed a significant difference at 60 min after the surgery began till the end (P<0.05). TPVB+GA exhibited excellent analgesic and sedative-sparing effects compared to GA alone (P<0.001), though it increased norepinephrine consumption due to hypotension (P<0.001). Conclusion: Although thorough warming strategies were used, TPVB combined with GA remarkably reduced the body temperature, which is an easily neglected side effect. Further studies on the most effective precautions are needed to optimize the clinical use of TPVB.

Auts2 regulated autism-like behavior, glucose metabolism and oxidative stress in mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by abnormal social behavior and communication. The autism susceptibility candidate 2 (AUTS2) gene has been associated with multiple neurological diseases, including ASD. Glucose metabolism plays an important role in social behaviors associated with ASD, but the potential role of AUTS2 in glucose metabolism has not been studied. Here, we generated Auts2flox/flox; Emx1Cre+ conditional knockout mice with Auts2 deletion specifically in Exm1-positive neurons in the brain (Auts2-cKO mice) to evaluate the effects of Auts2 knockdown on social behaviors and metabolic pathways. Auts2-cKO mice exhibited ASD-like behaviors, including impaired social interactions and repetitive grooming behaviors. At the molecular level, we found that Auts2 knockdown reduced brain glucose uptake and inhibited the pentose phosphate pathway. Auts2 knockdown also resulted in signs of oxidative stress, and we documented increased levels of reactive oxygen species and malondialdehyde as well as decreased levels of antioxidant molecules, including glutathione and superoxide dismutases in Auts2-cKO mouse brains compared to controls. Finally, Auts2 knockdown significantly disrupted mitochondrial homeostasis and inhibited activity of the SIRT1-SIRT3 axis. Taken together, our findings indicate that loss of AUTS2 expression in Emx1-expressing cells induces multiple changes in metabolic pathways that have been linked to the pathology of ASD. Further characterization of the role of AUTS2 in Emx1-expressing cells in regulating the metabolism of brain neurons may identify opportunities to treat ASD and AUTS2-deficiency disorders with metabolism-targeted therapies.