Purpose:This study aimed to compare the quality of postoperative recovery between esketamine-based opioid-free anesthesia (OFA) and opioid-based anesthesia (OBA) in patients undergoing laparoscopic transabdominal preperitoneal (TAPP) repair. Patients and Methods:In this prospective, randomized, double-blind, noninferiority trial, 126 adults scheduled for elective laparoscopic TAPP repair were randomized to OFA (n = 63) or OBA (n = 63) group. The OFA group received esketamine (0.5 mg·kg-1 induction, 0.4-0.5 mg·kg-1·h-1 maintenance), while the OBA group received sufentanil (0.4 μg·kg-1 induction) and remifentanil (0.1-0.2 μg·kg-1·min-1 maintenance). The primary outcome was the 15-item Quality of Recovery (QoR-15) score at 24 hours postoperatively, with a noninferiority margin of -8. Secondary outcomes included pain scores, rescue analgesia, sleep quality, safety outcomes. Results:The OFA group showed a higher QoR-15 score at 24 hours postoperatively than the OBA group (median difference: 2; median [IQR]: 129 [125 to 132] vs 127 [123 to 130]; 95% CI, 0 to 4; P=0.014). Pruritus incidence was lower (P=0.027), vasopressor use was reduced (P = 0.012), and hypotensive episodes tended to be fewer (P=0.106) in the OFA group. Pain scores on coughing at 24 and 48 hours postoperatively were also lower in the OFA group (P=0.002 and P< 0.001, respectively). Conclusion:Esketamine-based OFA provided a noninferior quality of postoperative recovery compared with OBA in patients undergoing laparoscopic TAPP repair, offering a safer alternative to OFA regimens that minimizes opioid-related complications while maintaining perioperative comfort and supporting enhanced recovery.

1. Propofol Hypersensitivity in Valvular Disease: Valvular heart disease (VD) patients exhibited 34

Purpose:Anesthesia management strategies in elderly patients undergoing total knee arthroplasty (TKA) are critical to the postoperative quality of recovery (QoR), and changes in electroencephalogram (EEG) associated with anesthesia drugs may play an important role in this process. This study aimed to determine the effects of different doses of dexmedetomidine on postoperative QoR in elderly TKA patients, and whether there is a correlation with specific EEG changes. Methods:In this randomized controlled trial, elderly patients (aged ≥ 60 years) undergoing elective TKA were randomly allocated in a 1:1:1 ratio to 0.6 μg/kg/h dexmedetomidine (Group D2), 0.3 μg/kg/h dexmedetomidine (Group D1) and saline (Group N). On postoperative days 1 and 3, the15-item Quality of Recovery (QoR-15) scale was used to evaluate the postoperative recovery of patients among the three groups. Perioperative EEG data were also recorded. Results:The difference of QoR-15 scores on postoperative day 1 was significant for Group D2 vs Group N (126 [123-129] points vs 120 [116-123] points; median difference, 6 points [95% CI, 4 to 8]; P < 0.001) and Group D2 vs Group D1 (126 [123-129] points vs 122 [118-126]; median difference, 4 points [95% CI, 2 to 5]; P = 0.001), but not for Group D1 vs Group N. However, no significant difference was observed in the global and dimensional QoR-15 scores on postoperative day 3 among the three groups. Intraoperative EEG power spectra analysis revealed a decrease in α oscillation peak power and an increase in slow oscillation peak power in Group D1 and Group D2, compared with Group N. In addition, the slow oscillation peak power exhibited weak positive correlations with QoR-15 scores on postoperative day 1 (r = 0.319, P < 0.001). Conclusion:A loading dose of dexmedetomidine (0.5 μg/kg) infused within 10 minutes before anesthesia induction, followed by a maintenance at 0.6 μg/kg/h, improved QoR-15 on postoperative day 1 in elderly TKA patients, which may be partly related to the fact that dexmedetomidine deepens anesthesia by increasing the slow oscillation peak power in the appropriate range.

BACKGROUND:Cough reflex during extubation can lead to complications such as increased bleeding and hemodynamic instability, especially in thyroidectomy, therefore, effective suppression of cough reflex is clinically important. The aim of the study was to investigate the inhibitory effect of dexmedetomidine combined with lidocaine on the cough reflex during extubation in thyroidectomy. METHODS:A total of 180 female patients, aged 18 to 65 years, undergoing elective thyroidectomy under general anesthesia, were randomized into 3 groups: dexmedetomidine combined with lidocaine (Dex-Lido group, n = 60), lidocaine alone (Lido group, n = 60), or normal saline (Control group, n = 60). Before tracheal intubation, patients in the Dex-Lido group received dexmedetomidine combined with 2% lidocaine spray, those in the Lido group received 2% lidocaine spray, and those in the Control group received 0.9% normal saline spray, applied to the supraglottic, glottic, and subglottic areas. The primary outcome was the incidence of cough reflex at extubation. Secondary outcomes included cough severity, postoperative sore throat, hoarseness, nausea, and vomiting, as well as the need for analgesics and antiemetics, pain levels, sedation scores, and length of hospital stay. RESULTS:The incidence of cough reflex during extubation was significantly lower in both the Dex-Lido and Lido groups compared to the Control group (23% vs 70%; odds ratio [OR], 0.13; 95% confidence interval [CI], 0.06-0.29; P < .001 for Dex-Lido; 47% vs 70%; OR, 0.38; 95% CI, 0.18-0.79]; P = .010 for Lido), with a statistically significant difference between the Dex-Lido and Lido groups (23% vs 47%; OR, 0.35; 95% CI, 0.16-0.76; P = .007). Additionally, the severity of the cough reflex was markedly lower in the Dex-Lido group compared to the Control group (8/60 vs 26/60; OR, 0.20; 95% CI, 0.08-0.50; P < .001). CONCLUSIONS:The combination of dexmedetomidine and lidocaine laryngopharynx spray effectively suppresses the cough reflex during extubation, reduces postoperative sore throat, and stabilizes hemodynamics in female patients undergoing thyroid surgery.

Nanomaterials exhibit significant potential in tumor diagnosis and treatment due to their unique physicochemical properties, for example, retention and permeability, environment-responsiveness, and so on. Particularly, the development of photothermal nanomaterials has brought new opportunities for biomedical, especially in the fields of tumor diagnosis and therapy. However, the application of nanomaterials in biomedicine often encounters considerable challenges in terms of biocompatibility, which hinders their clinical translation. However, carriers constructed from biocompatible nanomaterials hold promising prospects. Moreover, the limitations of single-agent tumor therapy highlight the importance of synergy therapy in clinical practice. Among various nanomaterials, polydopamine (PDA), a synthetic analog of natural melanin, not only possesses widespread sources and excellent biocompatibility, but also features biodegradability, easily modifiable surfaces, and superior photothermal conversion performance. Furthermore, the aromatic ring structure on the surface of PDA, containing functional groups such as catechol, amine, and imine, endows PDA with strong adhesive properties, which enables the loading of drug molecules via π-π interactions and achieves photothermal-based tumor synergy therapy. These characteristics give PDA a unique advantage in tumor synergy therapy. Therefore, this review summarizes and reviews various multifunctional drug carriers prepared based on PDA and their applications in tumor photothermal synergy therapy, thus providing insights for the future design of more diverse and intelligent drug delivery systems based on PDA.

STUDY OBJECTIVE:Postoperative pulmonary complications (PPCs), the predominant complications following lung surgery, are closely associated with intraoperative fluid therapy. This study investigates whether continuous low-dose norepinephrine infusion combined with goal-directed fluid therapy (GDFT) reduced the risk of PPCs after lung surgery relative to either GDFT alone or standard fluid treatment. DESIGN:A prospective, randomized controlled trial. SETTING:The First Affiliated Hospital of Anhui Medical University, Anhui, China. PATIENTS:The study included 184 patients undergoing elective thoracoscopic lung resection surgery. INTERVENTIONS:Patients were randomized into three groups based on different fluid treatment regimens: Group C received standard fluid treatment, Group G received GDFT, and Group N received continuous low-dose norepinephrine infusion combined with GDFT. MEASUREMENTS:The primary outcome was the incidence of PPCs, including respiratory infection, atelectasis, pneumothorax, pleural empyema, respiratory failure, pulmonary embolism and bronchopleural fistula, during the postoperative hospital stay. Secondary outcomes were hemodynamic variables and arterial blood gases. Additional recorded parameters included other postoperative complications such as bleeding, postoperative re-intubation, re-hospitalization within 30 days, and the length of hospital stay. MAIN RESULTS:Group N showed a significantly lower PPCs incidence during hospitalization compared to Group C (11.5 % vs 27.9 %; odds ratio, 2.98; 95 % confidence interval, 1.17-8.31; P = 0.023). No significant difference in PPCs was found between Group N and Group G (11.5 % vs 14.5 %; odds ratio, 1.31; 95 % confidence interval, 0.46-3.91; P = 0.616). Additionally, there were no significant differences among the three groups in the components of PPCs. Group N showed higher mean arterial pressure and stroke volume index intraoperatively compared to Group C. CONCLUSIONS:Continuous low-dose norepinephrine infusion combined with GDFT reduced PPCs incidence in elective lung surgery patients compared with standard fluid management, but showed no difference compared to GDFT alone. CLINICAL TRIAL REGISTRATION:ChiCTR2200064081.

Background:Myoclonus is a common problem during induction of anesthesia with etomidate. A variety of agents, including opioids and lidocaine, reduced the incidence of myoclonus. However, there is no reported literature evaluating the effect of esketamine pretreatment on etomidate-induced myoclonus. We investigated the influence of pretreatment with esketamine on the incidence of etomidate-induced myoclonus. Methods:This is a prospective, double-blind, and randomized controlled trial. One hundred patients aged 18-65 scheduled for elective surgery under general anesthesia (including urology surgery, gynaecology surgery, general surgery, and thoracic surgery) were randomly allocated into two groups, each consisting of 50 patients. Esketamine was pretreated with 0.1 mg/kg 60 s before the initiation of etomidate in Group ESK, while normal saline was administered as the placebo (Group C). During the first 1 minute after etomidate administration, myoclonus incidence and severity were assessed. In addition, we measured the hemodynamic changes and side effects of esketamine before administering etomidate. Results:In group ESK, 14 patients (28%) had myoclonus (degrees of myoclonus: mild 2, moderate 7, severe 5), and 32 patients (64%) in group C (mild 6, moderate 5, severe 21) (P< 0.001). In group ESK, myoclonus incidence and severity were significantly lower than in group C (P< 0.001). Conclusion:Esketamine 0.1mg/kg IV pretreatment significantly reduce the incidence and the severity of severe myoclonus of etomidate-induced myoclonus without significant adverse effects.

Background Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. Methods Gut microbiota, cytokines, and five dementia types, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson’s disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. Results There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. Conclusions Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.

Hearing impairment is a global health problem. Stem cell therapy has become a cutting-edge approach to tissue regeneration. In this review, the recent advances in stem cell therapy for hearing loss have been discussed. Nanomaterials can modulate the stem cell microenvironment to augment the therapeutic effects further. The potential of combining nanomaterials with stem cells for repairing and regenerating damaged inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) has also been discussed. Stem cell-derived exosomes can contribute to the repair and regeneration of damaged tissue, and the research progress on exosome-based hearing loss treatment has been summarized as well. Despite stem cell therapy's technical and practical limitations, the findings reported so far are promising and warrant further investigation for eventual clinical translation.

OBJECTIVE:This study aimed to compare the ability of three frailty assessments to predict adverse outcomes after elective gastrointestinal surgery and analyze how frailty assessments impact the American Society of Anesthesiologists (ASA) risk prediction model.METHODS:Frailty was measured using the FRAIL scale, Fried Phenotype (FP), and Clinical Frailty Scale (CFS), alongside ASA assessments before surgery. Univariate and logistic regression analyses were used to determine the predictive value of each method. The predictive abilities of the tools were assessed by the area under the receiver operating characteristic curves (AUCs) and their 95% confidence intervals (CIs).RESULTS:After adjusting for age and other risk factors, logistic regression analysis revealed significant positive associations between preoperative frailty and postoperative total adverse systemic complications (odds ratios [ORs] [95% CIs]: FRAIL, 1.297 [0.943-1.785]; FP, 1.317 [0.965-1.798]; CFS, 2.046 [1.413-3.015]; P < 0.001). The CFS was the best predictor of any adverse systemic complications (AUC, 0.696; 95% CI, 0.640-0.748). The predictive abilities of the FRAIL scale (AUC, 0.613; 95% CI, 0.555-0.669) and FP (AUC, 0.615; 95% CI, 0.557-0.671) were similar. The CFS and ASA assessment combined (AUC, 0.697; 95% CI, 0.641-0.749) had a statistically improved AUC compared to the ASA assessment alone (AUC, 0.636; 95% CI, 0.578-0.691), illustrating their value for predicting any adverse systemic complications.CONCLUSION:Frailty instruments enhance the accuracy of predicting postoperative outcome in older adults. Clinicians should add frailty assessments before preoperative ASA, particularly the CFS, given its ease of use and clinical feasibility.

Ethnopharmacological relevance: Verbenalin is a major compound in Verbena officinalis L. Verbena officinalis L was first recorded in the 'Supplementary Records of Famous Physicians.' Verbenalin (VE) is its active constituent and has been found to have many biological effects, including anti-obesity, anti-inflammatory, and antioxidant activities, removing jaundice, and treating malaria. It could treat lump accumulation, dysmenorrhea, throat obstruction, edema, jaundice, and malaria. Palmitic acid (PA), oleic acid (OA), ethanol, and acetaminophen liver injuries have been proven to benefit from verbenalin.Aim of the study: To study the effects of verbenalin on the prevention of alcoholic steatohepatitis (ASH) through the regulation of oxidative stress and mitochondrial dysfunction by regulating MDMX (Murine double minute X)/ PPAR alpha (Peroxisome proliferator-activated receptor alpha)-mediated ferroptosis. Material and methods: C57BL/6 mice treated with alcohol followed by the Gao-Binge protocol were administered verbenalin by gavage simultaneously. The mitochondrial mass and morphology were visualized using TEM. AML-12 cells were stimulated with ethanol to mimic ASH in vitro. Western blotting, co-immunoprecipitation, and kit determination were simultaneously performed. The target protein of verbenalin was identified by molecular docking, and cellular thermal shift assay (CETSA) further confirmed its interactions. Results: Verbenalin alleviates oxidative stress and ferroptosis in alcohol-associated steatohepatitis. To elucidate the molecular mechanism by which verbenalin inhibits abnormal mitochondrial dysfunction, molecular docking was performed, and MDMX was identified as the target protein of verbenalin. CETSA assays revealed a specific interaction between MDMX and verbenalin. Co-immunoprecipitation demonstrated that PPAR alpha played a critical role in promoting the ability of MDMX to affect ferroptosis. Verbenalin regulates MDMX/PPAR alpha-mediated ferroptosis in AML-12 cells.Conclusion: Verbenalin regulates ferroptosis and highlights the therapeutic potential of verbenalin and ferroptosis inhibition in reducing alcoholic steatohepatitis.

EEG monitoring techniques are receiving increasing clinical attention as a common method of reflecting the depth of sedation in the perioperative period. The influence of depth of sedation indices such as the bispectral index (BIS) generated by the processed electroencephalogram (pEEG) machine to guide the management of anesthetic depth of sedation on postoperative outcome remains controversial. This research was designed to decide whether an anesthetic agent exposure determined by raw electroencephalogram (rEEG) can influence anesthetic management and cause different EEG patterns and affect various patient outcomes. A total of 141 participants aged ≥ 60 years undergoing abdominal major surgery were randomized to rEEG-guided anesthesia or routine care group. The rEEG-guided anesthesia group had propofol titrated to keep the rEEG waveform at the C-D sedation depth during surgery, while in the routine care group the anesthetist was masked to the patient’s rEEG waveform and guided the anesthetic management only through clinical experience. The primary outcome was the presence of postoperative complications, the secondary outcomes included intraoperative anesthetic management and different EEG patterns. There were no statistically significant differences in the occurrence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. Further EEG analysis revealed that lower frontal alpha power was significantly associated with a higher incidence of POD, and that rEEG-guidance not only reduced the duration of deeper anesthesia in patients with lower frontal alpha power, but also allowed patients with higher frontal alpha power to receive deeper and more appropriate depths of anesthesia than in the routine care group. In elderly patients undergoing major abdominal surgery, rEEG-guided anesthesia did not reduce the incidence of postoperative respiratory, circulatory, neurological and gastrointestinal complications. rEEG-guided anesthesia management reduced the duration of intraoperative BS in patients and the duration of over-deep sedation in patients with lower frontal alpha waves under anesthesia, and there was a strong association between lower frontal alpha power under anesthesia and the development of POD. rEEG-guided anesthesia may improve the prognosis of patients with vulnerable brains by improving the early identification of frail elderly patients and providing them with a more effective individualized anesthetic managements.

Background: Hastatoside is an iridoid glycoside extracted from the herb, Verbena officinalis, that exerts various pharmacological effects, including anti-inflammatory, sleep-promoting, and analgesic effects. However, only a few studies have reported the efficacy of hastatoside in liver fibrosis. Liver fibrosis is a pathophysiological process, and its persistence can seriously affect the quality of life and well-being of the patients. Hypothesis/purpose: This study aimed to investigate the role of hastatoside on liver fibrosis and its possible underlying mechanisms. Methods: C57BL/6 J mice with carbon tetrachloride (CCl4)-induced hepatic fibrosis were used as the in vivo models. Histological features of the liver were observed using Masson's trichrome and hematoxylin-eosin staining. Alanine aminotransferase and aspartate aminotransferase levels and the hepatic fibrosis indices (type 3 procollagen, laminin, and hyaluronic acid) were measured using corresponding assay kits. LX-2 human hepatic stellate cells (HSCs) stimulated with the transforming growth factor beta 1 were used as the vitro models. Transfection of the glycogen synthase kinase (GSK)- 3 beta small interfering RNA (siRNA) and beta-catenin plasmids was also performed in vitro. Protein levels of GSK-3 beta, phospho-GSK-3 beta (Ser 9), alpha-smooth muscle actin, collagen type I alpha 1, c-Myc, cyclin D1, and beta-catenin were determined via western blotting. Moreover, the p-GSK-3 beta:GSK-3 beta ratio was calculated to determine the GSK-3 beta activity. Results: Hastatoside prevented CCl4-induced liver injury and histological damage. It inhibited the upregulation of alpha-SMA and Col1 alpha 1 levels in a CCl4-induced mouse hepatic fibrosis model. In vitro, hastatoside inhibited the proliferation and activation of HSCs by decreasing the expression levels of cyclin D1 and c-Myc and the pro-portion of LX-2 cells activated in the G0/G1 phase. Molecular docking results showed that hastatoside bound to GSK-3 beta. Hastatoside significantly increased the GSK-3 beta activity and inhibited the downstream effector expression of beta-catenin. Conclusion: These findings suggest that hastatoside can bind to GSK-3 beta and promote its activity, while inhibiting the GSK-3 beta downstream effector expression of beta-catenin, thereby inhibiting the activation and proliferation of HSCs, which further prevents the development of liver fibrosis. These results provide innovative insights into the underlying liver fibrosis. Moreover, hastatoside is a potential anti-fibrosis monomer that can potentially be used for the treatment of liver fibrosis.

Dexmedetomidine, as an α2-adrenoceptor agonist, plays anti-sympathetic, sedative and analgesic roles in perioperative period. Also, dexmedetomidine can reduce the minimal alveolar concentration (MAC) of sevoflurane and the risk of postoperative cognitive dysfunction (POCD) induced by sevoflurane anesthesia. But so far, the electroencephalogram (EEG) mechanism of dexmedetomidine deepening sevoflurane anesthesia is not clear. In this study, by analyzing the changes of the power spectrum and bicoherence spectrum of EEG before and after dexmedetomidine infusion, the EEG mechanism of dexmedetomidine deepening sevoflurane anesthesia was studied. We analyzed dexmedetomidine-induced changes in power spectrum and bicoherence spectrum in 23 patients under sevoflurane anesthesia. After anesthesia induction, the sevoflurane concentration was maintained at 0.8 MAC for 15 min, and then dexmedetomidine was administered at a loading dose of 0.8 μg/kg in 10 min, followed by a maintenance rate of 0.5 μg⋅kg–1⋅h–1. Frontal EEG data from 5 min before and 10 min after dexmedetomidine infusion were compared. After dexmedetomidine infusion, the mean α power peak decreased from 6.09 to 5.43 dB and shifted to a lower frequency, the mean θ bicoherence peak increased from 29.57 to 41.25% and shifted to a lower frequency, and the median α bicoherence peak increased from 41.49 to 46.36% and shifted to a lower frequency. These results demonstrate that dexmedetomidine deepens sevoflurane anesthesia, and enhances α and θ bicoherences while shifting peak values of these bands to lower frequencies through regulating thalamo-cortical reverberation networks probably.

PURPOSE:Pressure-controlled volume-guaranteed (PCV-VG) combines the characteristics of pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV). It has been reported that PCV-VG decreases airway pressure and improves oxygenation among the adult group. In this study, the respiratory dynamics of PCV-VG and VCV are compared in pediatric patients ventilated with laryngeal mask airway and underwent laparoscopic hernia of the sac ligation.PATIENTS AND METHODS:Sixty-four pediatric patients were included in this prospective, randomized clinical trial. Pediatric patients were randomly allocated to receive VCV and PCV-VG ventilation during the general anesthesia. The hemodynamic and respiratory variables were recorded at the time when laryngeal mask airway was placed, pneumoperitoneum began, 5 mins after pneumoperitoneum began, pneumoperitoneum ended, and the operation ended respectively. The respiratory adverse events were recorded after the operation and on the first day after the operation. In this study, respiratory adverse events are defined as cough, hoarseness, hypoxemia, laryngospasm, bronchospasm, and sore throat.RESULTS:There was no statistical difference in hemodynamic variables at all time points between the two groups. Compared to the VCV group, peak airway pressure (Ppeak) and plateau airway pressure in the PCV-VG group decreased significantly. Pulmonary dynamic compliance (Cydn) in the PCV-VG group was significantly higher than that in the VCV group. The respiratory adverse events appeared to have no statistical difference between VCV and PCV groups.CONCLUSION:PCV-VG provides a lower Ppeak and better Cydn in pediatric patients compared with the VCV group during laparoscopic surgery. The results suggested that PCV-VG may be a superior way of mechanical ventilation for pediatric patients who ventilated with laryngeal mask airway and experienced laparoscopic surgery.

Abstract Background Although dexmedetomidine (Dex) is known to reduce bispectral index (BIS) values and propofol dosage, there is little information regarding raw electroencephalography (EEG) changes related to Dex deepening of propofol general anesthesia (GA). This study investigated the Dex effects on propofol GA via analysis of EEG changes. Methods A study cohort of 21 surgical patients (age range, 20–60 years) categorized as American Society of Anesthesiologists (ASA) class I or II was enrolled. We used time-varying spectral and bicoherence methods to compare electroencephalogram signatures 5 min before versus 10 min after intravenous Dex injection under propofol GA. The means and medians are reported with 95% confidence intervals (CIs) and inter-quartile ranges (IQRs), respectively. Results Dex augmented the slow waves power and theta (θ) oscillation bicoherence peak from a mean (95% CI) of 22.1% (19.0, 25.2) to 25.2% (21.8, 28.6). Meanwhile, Dex reduced alpha (α) peak power and bicoherence from 3.5 dB (1.0, 6.0) and 41.5% (34.0, 49.0) to 1.7 dB (− 0.6, 4.0) and 35.4% (29.0, 41.8), respectively, while diminishing the median frequency of α oscillation peak values and the mean frequency of α peaks in bicoherence spectra from 12.0 Hz (IQR 11.2, 12.6) and 11.7 Hz (11.3, 12.2) to 11.1 Hz (IQR 10.3, 11.8) and 11.2 Hz (10.9, 11.6), respectively. Conclusions Profound EEG changes support the supposition that Dex enhances propofol-induced GA from a moderate to a deeper state. The present findings provide a theoretical basis and reference regarding protocols aimed at reducing anesthetic/sedative dosage while maintaining sufficient depth of GA. Clinical trial registration ChiCTR, ChiCTR1900026955 . Registered on 27 October 2019

The liver accounts for the largest proportion of macrophages in all solid organs of the human body. Liver macrophages are mainly composed of cytolytic cells inherent in the liver and mononuclear macrophages recruited from the blood. Monocytes recruitment occurs mainly in the context of liver injury and inflammation and can be recruited into the liver and achieve a KC-like phenotype. During the immune response of the liver, macrophages/KC cells release inflammatory cytokines and infiltrate into the liver, which are considered to be the common mechanism of various liver diseases in the early stage. Meanwhile, macrophages/KC cells form an interaction network with other liver cells, which can affect the occurrence and progression of liver diseases. From the perspective of liver disease treatment, knowing the full spectrum of macrophage activation, the underlying molecular mechanisms, and their implication in either promoting liver disease progression or repairing injured liver tissue is highly relevant from a therapeutic point of view. Kv1.3 is a subtype of the voltage-dependent potassium channel, whose function is closely related to the regulation of immune cell function. At present, there are few studies on the relationship between Kv1.3 and liver diseases, and the application of its blockers as a potential treatment for liver diseases has not been reported. This manuscript reviewed the physiological characteristics of Kv1.3, the relationship between Kv1.3 and cell proliferation and apoptosis, and the role of Kv1.3 in a variety of liver diseases, so as to provide new ideas and strategies for the prevention and treatment of liver diseases. In short, by understanding the role of Kv1.3 in regulating the functions of immune cells such as macrophages, selective blockers of Kv1.3 or compounds with similar functions can be applied to alleviate the progression of liver diseases and provide new ideas for the prevention and treatment of liver diseases.

Objective:To investigate the effects of sevoflurane at different concentrations on epileptic discharge during general anesthesia induction in children.Methods:Sixty-six pediatric patients of both sexes, aged 3-12 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective tonsillectomy or (and) adenoidectomy under general anesthesia, were divided into 3 groups ( n=22 each) using a random number table method: 4% sevoflurane group (L group), 6% sevoflurane group (M group) and 8% sevoflurane group (H group). Combined intravenous-inhalational anesthesia was used during operation.The occurrence of epileptiform discharge during induction period and delirium during emergence was recorded.The correlation between epileptiform discharge and delirium during emergence was analyzed using χ2 test. Results:Compared with group L, the incidence of excitatory epileptiform discharge was significantly decreased in group H, and the incidence of epileptiform discharge was significantly reduced in group M and group H ( P<0.05). There was no significant difference in the incidence of excitatory epileptiform discharge and epileptiform discharge between group M and group H ( P>0.05). There was no significant difference in the incidence of inhibitory epileptiform discharge and delirium during emergence among the three groups ( P>0.05). The occurrence of epileptiform discharges and excitatory epileptiform discharges was correlated with the occurrence of delirium during emergence ( P<0.05), and the occurrence of inhibitory epileptiform discharges was not correlated with the occurrence of delirium during emergence ( P>0.05). Conclusion:Low concentration (4%) of sevoflurane can lead to an increase in excitatory epileptiform discharges during emergence from general anesthesia in children.

Objective:To evaluate the effect of sedation management based on visual analysis of electroencephalography (EEG) on postoperative delirium in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods:Eighty patients, aged ≥ 18 yr, of American Society of Anesthesiologists physical status Ⅲ or Ⅳ, with New York Heart Association Ⅱ-Ⅳ, scheduled for elective cardiac valve replacement with CPB, were randomly divided into visual analysis of EEG-guided sedation management group (group A, n=40) and BIS-guided sedation management group (group B, n=40). The target plasma concentration of propofol was adjusted to maintain the depth of anaesthesia at grade C or grade D in group A and BIS value at 40-60 in group B. Propofol consumption during CPB and total consumption of propofol during surgery, requirement for vasoactive agents during surgery, and parameters of intraoperative arterial blood gas analysis were recorded.Postoperative delirium was evaluated using Confusion Assessment Method for the Intensive Care Unit (ICU) at 1-7 days after surgery.Extubation time, length of ICU stay, length of postoperative hospital stay and intraoperative awareness were also recorded. Results:Compared with group B, the length of postoperative hospital stay was significantly shortened, the incidence of postoperative delirium was decreased, and no significant change was found in the parameters of arterial blood gas analysis, propofol consumption, requirement for vasoactive agents, extubation time, or length of postoperative ICU stay in group A ( P<0.05). No intraoperative awareness occurred in both groups. Conclusion:Sedation management based on visual analysis of EEG is helpful in decreasing the development of postoperative delirium in the patients undergoing cardiac valve replacement with CPB.

Autophagy allows cancer cells to respond changes in nutrient status by degrading and recycling non-essential intracellular contents. Inhibition of autophagy combined with nutrient deprivation is an effective strategy to treat cancer. Pain is a primary determinant of poor quality of life in advanced cancer patients, but there is currently no satisfactory treatment. In addition, effective treatment of cancer does not efficiently relieve cancer pain, but may increase pain in many cases. Hence, few studies focus on simultaneous cancer therapy and pain relief, and made this situation even worse. Method: Ropivacaine was loaded into tumor-active targeted liposomes. The cytotoxicity of ropivacaine-based combination therapy in B16 and HeLa cells were tested. Moreover, a mice model of cancer pain which was induced by inoculation of melanoma near the sciatic nerve was constructed to assess the cancer suppression and pain relief effects of ropivacaine-based combination therapy. Results: Ropivacaine and ropivacaine-loaded liposomes (Rop-DPRL) were novelly found to damage autophagic degradation. Replicated administration of Rop-DPRL and calorie restriction (CR) could efficiently repress the development of tumor. In addition, administration of Rop-DPRL could relieve cancer pain with its own analgestic ability in a short duration, while repeated administration of Rop-DPRL and CR resulted in continuous alleviation of cancer pain through reduction of VEGF-A levels in advanced cancer mice. Further, dual inhibition of phosphorylation of STAT3 at Tyr705 and Ser727 by Rop-DPRL and CR contribute to the reduction of VEGF-A. Conclusion: Combination therapy with Rop-DPRL and nutrient deprivation simultaneously suppresses cancer growth and relieves cancer pain.