Interleukin-33 ameliorates perioperative neurocognitive disorders by modulating microglial state.

Perioperative neurocognitive disorders (PND) are cognitive dysfunctions that usually occur in elderly patients after anesthesia and surgery. Microglial overactivation is a key underlying mechanism. Interleukin-33 (IL-33) is a member of the IL-1 family that orchestrates microglial function. In the present study, we explored how IL-33, which regulates microglia, contributes to cognitive improvement in a male mouse model of PND. An exploratory laparotomy was performed to establish a PND model. The expression levels of IL-33 and its receptor ST2 were evaluated using Western blot. IL-33/ST2 secretion, microglial density, morphology, phagocytosis of synapse, and proliferation, and dystrophic microglia were assessed using immunofluorescence. Synaptic plasticity was measured using Golgi staining and long-term potentiation. The Morris water maze and open field test were used to evaluate cognitive function and anxiety. Hippocampal expression of IL-33 and ST2 were elevated on postoperative day 3. We confirmed that IL-33 was secreted by astrocytes and neurons, whereas ST2 mainly colocalized with microglia. IL-33 treatment induced microgliosis after anesthesia and surgery. These microglia had larger soma sizes and shorter and fragmented branches. Compared to the Surgery group, IL-33 treatment reduced the synaptic phagocytosis of microglia and increased microglial proliferation and dystrophic microglia. IL-33 treatment also reversed the impaired synaptic plasticity and cognitive function caused by anesthesia and surgery. In conclusion, these results indicate that IL-33 plays a key role in regulating microglial state and synaptic phagocytosis in a PND mouse model. IL-33 treatment has a therapeutic potential for improving cognitive dysfunction in PND.

Effect of continuous measurement and adjustment of endotracheal tube cuff pressure on postoperative sore throat in patients undergoing gynecological laparoscopic surgery: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complication following endotracheal tube removal, and effective preventive strategies remain elusive. This trial aimed to determine whether actively regulating intraoperative cuff pressure below the tracheal capillary perfusion pressure threshold could effectively reduce POST incidence in patients undergoing gynecological laparoscopic procedures. METHODS: This single-center, randomized controlled superiority trial allocated 60 patients scheduled for elective gynecological laparoscopic procedures into two groups: one designated for cuff pressure measurement and adjustment (CPMA) group, and a control group where only cuff pressure measurement was conducted without any subsequent adjustments. The primary outcome was POST incidence at rest within 24 h post-extubation. Secondary outcomes included cough, hoarseness, postoperative nausea and vomiting (PONV) incidence, and post-extubation pain severity. RESULTS: The incidence of sore throat at rest within 24 h after extubation in the CPMA group was lower than in the control group, meeting the criteria for statistically significant superiority based on a one-sided test (3.3% vs. 26.7%, P < 0.025). No statistically significant differences were observed in cough, hoarseness, or pain scores within 24 h post-extubation between the two groups. However, the CPMA group had a higher incidence of PONV compared to the control group. Additionally, the control group reported higher sore throat severity scores within 24 h post-extubation. CONCLUSIONS: Continuous monitoring and maintenance of tracheal tube cuff pressure at 18 mmHg were superior to merely monitoring without adjustment, effectively reducing the incidence of POST during quiet within 24 h after tracheal tube removal in gynecological laparoscopic surgery patients. TRIAL REGISTRATION: The study was registered at www.chictr.org.cn (ChiCTR2200064792) on 18/10/2022.

The predictive and prognostic value of risk factors in patients receiving hybrid coronary revascularization with postoperative pulmonary complications.

Background: The mortality rate of coronary artery disease ranks first in developed countries, and coronary revascularization therapy is an important cornerstone of its treatment. The postoperative pulmonary complications (PPCs) in patients receiving one-stop hybrid coronary revascularization (HCR) aggravate the dysfunction of multiple organs such as the heart and lungs, therefore increasing mortality. However, the risk factors are still unclear. The objective of this study was to explore the risk factors of PPCs after HCR surgery. Methods: In this study, the perioperative data of 311 patients undergoing HCR surgery were reviewed. All patients were divided into two groups according to whether the PPCs occurred. The baseline information and surgery-related indicators in preoperative laboratory examination, intraoperative fluid management, and anesthesia management were compared between the two groups. Results: Advanced age [odds ratio (OR): 1.065, 95% confidence interval (CI): 1.030-1.101, P<0.001], high body mass index (BMI; OR: 1.113, 95% CI: 1.011-1.225, P=0.02), history of percutaneous coronary intervention (PCI) surgery (OR: 2.831, 95% CI: 1.388-5.775, P=0.004), one-lung volume ventilation (OR: 3.804, 95% CI: 1.923-7.526, P<0.001), inhalation of high concentration oxygen (OR: 3.666, 95% CI: 1.719-7.815, P=0.001), the application of positive end-expiratory pressure (PEEP; OR: 2.567, 95% CI: 1.338-4.926, P=0.005), and long one-lung ventilation time (OR: 1.015, 95% CI: 1.006-1.023, P=0.001) may be risk factors for postoperative PPCs in patients undergoing one-stop coronary revascularization surgery. Using the above seven factors to jointly predict the risk of PPCs in patients undergoing one-stop coronary revascularization surgery, the receiver operating characteristic (ROC) curve showed an area under the curve (AUC) =0.873, 95% CI: 0.835-0.911, sensitivity: 84.81%, and specificity: 75.82%; the predictive model was shown to be effective. Conclusions: Patients undergoing HCR surgery with advanced age, high BMI, a history of PCI surgery, one-lung volume ventilation, inhalation of high concentration oxygen, use of PEEP, and prolonged single lung ventilation are more prone to PPCs.

Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial.

BACKGROUND: Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. METHODS: This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b-3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 µg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. DISCUSSION: This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Effects of opioid-free anaesthesia on postoperative nausea and vomiting in patients undergoing video-assisted thoracoscopic surgery (OFA-PONV trial): study protocol for a randomised controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication after general anaesthesia and is associated with morbidity and prolonged length of stay. Growing evidence suggest that opioid-free general anaesthesia (OFA) may reduce PONV in various surgical settings. We aim to evaluate the efficacy of OFA on the incidence of PONV compared with opioid-based anaesthesia among adults undergoing thoracoscopic surgery. METHODS: This is a prospective, single-centre, randomised controlled trial comparing OFA and opioid-based anaesthesia for thoracoscopic surgery. A total of 168 adults will be randomised with a 1:1 ratio to receive either opioid-free anaesthesia or opioid-based anaesthesia. The primary outcome will be the incidence of PONV within 24 h after operation. The secondary outcomes will include the severity of PONV, quality of recovery, pain at rest, 6-min walking test, and health-related quality of life after operation. DISCUSSION: The benefit-risk of OFA for patients after operation is contradictory in previous studies, so further study is required. This trial will focus on the effect of OFA on the incidence of PONV in patients undergoing thoracoscopic surgery. This trial adopts uniformed PONV and perioperative pain management, standardised randomised and blind, clear-cut inclusion and exclusion criteria, and standardised scales to assess the severity of PONV after surgery, the quality of postoperative recovery, and the health status at 6 months. The findings of this study will help to provide references to promote early recovery of patients after lung surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05411159. Registered on 9 June 2022.

Airway management for a patient with tracheobronchomegaly undergoing lobectomy: a case report.

BACKGROUND: Tracheobronchomegaly (TBM) is a rare disorder mainly characterized by dilatation and malacia of the trachea and major bronchi with diverticularization. This will be a great challenge for airway management, especially in thoracic surgery requiring one-lung ventilation. Using a laryngeal mask airway and a modified double-lumen Foley catheter (DFC) as a "blocker" may achieve one-lung ventilation. This is the first report introducing this method in a patient with TBM. CASE PRESENTATION: We present a 64-year-old man with TBM receiving left lower lobectomy. Preoperative chest computed tomography demonstrated a prominent tracheobronchial dilation and deformation with multiple diverticularization. The most commonly used double-lumen tube or bronchial blocker could not match the distorted airways. After general anesthesia induction, a 4# laryngeal mask was inserted, through which the modified DFC was positioned in the left main bronchus with the guidance of a fiberoptic bronchoscope. The DFC balloon was inflated with 10 ml air and lung isolation was achieved without any significant air leak during one-lung or two-lung ventilation. However, the collapse of the non-dependent lung was delayed and finally achieved by low-pressure artificial pneumothorax. The surgery was successful and the patient was extubated soon after the surgery. CONCLUSIONS: Using a laryngeal mask airway with a modified double-lumen Foley catheter acted as a bronchial blocker could be an alternative method to achieve lung isolation.

Overweight or Obesity among Chinese Han People with Schizophrenia: Demographic, Clinical and Cognitive Correlations.

People with schizophrenia are more likely to be afflicted by obesity or overweight compared to the general population. This study aimed to explore the incidence of overweight and obesity, clinical features and cognitive performance of Chinese Han patients with chronic schizophrenia who had overweight or obesity. We obtained data from 985 schizophrenia inpatients about overweight and obesity through body mass index (BMI). All patients were evaluated with the positive and negative syndrome scale, the Mini-mental State Examination (MMSE) and the repeated battery for evaluation of the neuropsychological status (RBANS) scale. We collected demographic and clinical data using self-reported questionnaires. We divided patients into normal weight (BMI < 24 kg/m2), overweight (24 ≤ BMI < 28 kg/m2) and obese (≥28 kg/m2) groups according to the Working Group on Obesity in China (WGOC) criteria. We compared the clinical data between the three groups and then conducted binary logistic regression and linear regression to assess variables that were significantly associated with overweight and obesity and higher BMI. Of the sample, 324 (32.9%) and 191 (19.4%) patients had overweight and obesity, respectively. Patients who had overweight and obesity were younger, had less education, had higher waist and hip circumferences, higher rates of diabetes and a higher sumPANSP score (compared with patients in the normal group, p < 0.05). There were more female patients with obesity (compared with patients in the normal and overweight groups, p < 0.05). Logistic regression analysis indicated that overweight and obesity were associated with sumPANSP (OR = 1.03, 95%CI = 1-1.061, p = 0.049) and diabetes (OR = 1.891, 95%CI = 1.255-2.849, p = 0.002). Further linear regression showed that age (B = -0.004, t = -2.83, p = 0.005), educational level (B = -0.037, t = -2.261, p = 0.024), diabetes (B = 0.133, t = 2.721, p = 0.007) and sumPANSP (B = 0.008, t = 2.552, p = 0.011) were risk factors for higher BMI. We did not find cognitive performance differences between patients with or without overweight and obesity. Overweight and obesity were associated with some demographic and clinical factors in patients with persistent schizophrenia.

Gender differences in the prevalence and clinical correlates of thyroid dysfunction in patients with first-episode and drug-naïve major depressive disorder with comorbid suicide attempts: a large cross-sectional study.

BACKGROUND: Gender differences in patients with major depressive disorder (MDD) are commonly reported; however, gender differences in first-episode and drug-naïve (FEDN) MDD patients with comorbid suicide attempts have not been reported. This study aimed to examine potential gender differences in the prevalence and clinical correlates of comorbid abnormal thyroid function (ATF) in FEDN MDD patients with comorbid suicide attempts. METHODS: A cross-sectional study of 1718 FEDN MDD patients was conducted. The demographic and clinical data were collected. The Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) were used to assess depression, anxiety and psychotic symptoms, respectively. Thyroid function parameters and blood glucose levels were measured. RESULTS: There was no gender difference in the prevalence of ATF between male (78.6%, 88/112) and female MDD patients (74.8%, 175/234) with comorbid suicide attempts. In the male and female subgroups, duration of disease, HAMD score, HAMA score, anti-thyroglobulin (TgAb), thyroid peroxidases antibody (TPOAb), diastolic blood pressure (DBP), systolic blood pressure (SBP), glucose level and the rate of psychotic symptoms were higher in patients with ATF than those without ATF in MDD with comorbid suicide attempt (all P < 0.05). There was a gender main effect only on SBP (F = 7.35, P = 0.007). Furthermore, binary logistic regression analysis showed that HAMD score, DBP and glucose levels were independently with ATF in both male and female MDD patients with comorbid suicide attempts. However, anxiety symptoms, psychotic symptoms and TPOAb levels were significantly associated with ATF only in female MDD patients with comorbid suicide attempts. CONCLUSION: Our study showed no gender differences in the prevalence of ATF in FEDN MDD patients with comorbid suicide attempts. Depression, DBP and glucose levels were associated with ATF in both male and female MDD patients with comorbid suicide attempts, whereas anxiety, psychotic symptoms and TPOAb level were correlated with ATF only in female MDD patients with suicide attempts.

Differences in the prevalence and clinical correlates of comorbid suicide attempts in patients with early- and late-onset major depressive disorder.

Objective: There are many studies on differences in the onset age of major depressive disorder (MDD) patients. However, study on differences in clinical correlates of suicide attempts between early- and late-onset MDD patients is limited. The aim of this study was to investigate the differences in the prevalence and clinical correlates of suicide attempts in patients with early- and late-onset MDD in China. Methods: A total of 1718 adult outpatients with MDD were recruited. Demographic and clinical data were collected. The 17-item Hamilton Rating Scale for Depression (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression-Severity (CGI-S) Scales were used to assess their depressive, anxiety, psychotic symptoms, and the severity of the clinical symptoms, respectively. Results: The prevalence of suicide attempts was higher in late-onset MDD patients (291/1369, 21.3%) than in early-onset MDD patients (55/349, 15.8%) (p = 0.023). However after Bonferroni correction no significant difference was found in the prevalence of suicide attempts in late-onset and late-onset MDD patients (p > 0.05). In both early- and late-onset groups, univariate analysis showed that the following characteristics were significantly associated with suicide attempts: HAMA, HAMD and PANSS positive subscale scores, thyroid stimulating hormone (TSH) levels, blood glucose levels, systolic blood pressure (SBP), and diastolic blood pressure (DBP). In both the early- and late-onset groups, the prevalence rates of severe anxiety disorder and psychotic symptoms were significantly higher in the suicide attempt group than in the non-suicide attempt group. In regression analysis, disease duration, TSH levels and HAMA score were independently associated with suicide attempts in the early-onset group, while TSH levels, HAMA and HAMD score were independently associated with suicide attempts in the late-onset group. Conclusion: This study suggests that suicide attempts are not frequent in early-onset outpatients with MDD compared with late-onset, and some clinical correlates are associated with suicide attempt in early- and late-onset MDD.

Transcutaneous electrical acupoint stimulation in adult patients receiving gastrectomy/colorectal resection: A randomized controlled trial.

BACKGROUND: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

Transforming Growth Factor ß1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders.

Perioperative neurocognitive disorder (PND) is a common complication of surgery and anesthesia, especially among older patients. Microglial activation plays a crucial role in the occurrence and development of PND and transforming growth factor beta 1 (TGF-ß1) can regulate microglial homeostasis. In the present study, abdominal surgery was performed on 12-14 months-old C57BL/6 mice to establish a PND model. The expression of TGF-ß1, TGF-ß receptor 1, TGF-ß receptor 2, and phosphor-smad2/smad3 (psmad2/smad3) was assessed after anesthesia and surgery. Additionally, we examined changes in microglial activation, morphology, and polarization, as well as neuroinflammation and dendritic spine density in the hippocampus. Behavioral tests, including the Morris water maze and open field tests, were used to examine cognitive function, exploratory locomotion, and emotions. We observed decreased TGF-ß1 expression after surgery and anesthesia. Intranasally administered exogenous TGF-ß1 increased psmad2/smad3 colocalization with microglia positive for ionized calcium-binding adaptor molecule 1. TGF-ß1 treatment attenuated microglial activation, reduced microglial phagocytosis, and reduced surgery- and anesthesia-induced changes in microglial morphology. Compared with the surgery group, TGF-ß1 treatment decreased M1 microglial polarization and increased M2 microglial polarization. Additionally, surgery- and anesthesia-induced increase in interleukin 1 beta and tumor necrosis factor-alpha levels was ameliorated by TGF-ß1 treatment at postoperative day 3. TGF-ß1 also ameliorated cognitive function after surgery and anesthesia as well as rescue dendritic spine loss. In conclusion, surgery and anesthesia induced decrease in TGF-ß1 levels in older mice, which may contribute to PND development; however, TGF-ß1 ameliorated microglial activation and cognitive dysfunction in PND mice.

Dopaminergic System in Promoting Recovery from General Anesthesia.

Dopamine is an important neurotransmitter that plays a biological role by binding to dopamine receptors. The dopaminergic system regulates neural activities, such as reward and punishment, memory, motor control, emotion, and sleep-wake. Numerous studies have confirmed that the dopaminergic system has the function of maintaining wakefulness in the body. In recent years, there has been increasing evidence that the sleep-wake cycle in the brain has similar neurobrain network mechanisms to those associated with the loss and recovery of consciousness induced by general anesthesia. With the continuous development and innovation of neurobiological techniques, the dopaminergic system has now been proved to be involved in the emergence from general anesthesia through the modulation of neuronal activity. This article is an overview of the dopaminergic system and the research progress into its role in wakefulness and general anesthesia recovery. It provides a theoretical basis for interpreting the mechanisms regulating consciousness during general anesthesia.

Effect of continuous measurement and adjustment of endotracheal tube cuff pressure on postoperative sore throat in patients undergoing gynecological laparoscopic surgery: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common postoperative complication after endotracheal tube removal. There are still no effective preventive methods for POST. The aim of this trial is to confirm whether maintaining intraoperative cuff pressure below the tracheal capillary perfusion pressure could effectively reduce the incidence of POST among patients undergoing gynecological laparoscopic surgery. METHODS: This study is a single-center, randomized, parallel-controlled, superiority trial with a 1:1 allocation ratio. Sixty patients whose age is between 18 and 65 years and scheduled for gynecological laparoscopic surgery will be randomized to the cuff pressure measurement and adjustment (CPMA) group and the only cuff pressure measurement without adjustment group (control group). The primary endpoint is the incidence of sore throat at rest within 24 h after extubation. The secondary endpoints include the incidence of cough, the incidence of hoarseness, the incidence of postoperative nausea and vomiting (PONV), POST, and pain intensity within 24 h after extubation. Blocked randomization will be conducted with a computer-generated central randomization online service. The blind method will be applied to subjects, data collectors, outcome evaluators, and statisticians. Outcome assessments will be performed at 0 h and 24 h post-extubation. DISCUSSION: This randomized controlled study hypothesizes that cuff pressure is the primary influencing factor of POST. By continuous monitoring of endotracheal tube cuff pressure and maintaining it within the range of 18-22 mmHg compared with only continuous measurement without adjustment, it aims to prove that continuous measurement and adjustment of endotracheal tube cuff pressure could be effective in reducing the incidence of POST in gynecological laparoscopic surgery patients. The result of this study could be used as a reference for future multicenter studies to confirm the effect of cuff pressure on POST and provides a scientific theoretical basis for preventing POST to further support comfort medicine. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200064792. Registered on 18 October 2022. This protocol (version 1.0, 16 March 2022) was approved by the Ethics Committee of Beijing Chaoyang Hospital.

Prevalence and clinical profile of abnormal glucose in first-episode and drug-naïve patients with major depressive disorder with comorbid abnormal thyroid function: a large-scale cross-sectional study.

BACKGROUND: The associated factors of abnormal glucose in patients with major depressive disorder (MDD) with comorbid abnormal thyroid function (ATF) remain unclear. To the best of our knowledge, this is the first study with a large sample size that examines the risk factors of abnormal glucose in first-episode drug-naïve (FEDN) MDD patients comorbid with ATF and includes clinical correlates and thyroid hormone levels. METHODS: A total of 1718 FEDN MDD patients were recruited. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were used to evaluate the symptoms of patients. Fasting blood glucose concentration and thyroid hormone levels were measured. RESULTS: The prevalence of abnormal glucose in MDD patients with comorbid ATF was 47.3%, which was 4.25 times higher than that in MDD patients without ATF (17.4%). Compared to those ATF patients without abnormal glucose, ATF patients with abnormal glucose scored higher on HAMD, HAMA and PANSS positive subscale, had a higher rate of suicide attempts, severe anxiety and psychotic symptoms, and had higher levels of thyroid-stimulating hormone (TSH), and thyroid peroxidases antibody (TPOAb) which were also correlated with abnormal glucose in MDD patients comorbid ATF (all P < 0.05). The combination of HAMD score and TSH could differentiate abnormal glucose from ATF. Further, TSH was independence-related with the concentration of fasting blood glucose in MDD patients with comorbid ATF. CONCLUSION: Our results demonstrate a high prevalence of abnormal glucose in MDD patients with comorbid ATF. Some clinical and thyroid function-related variables may be associated with abnormal glucose in MDD patients with comorbid ATF.

Luteoloside Prevents Sevoflurane-induced Cognitive Dysfunction in Aged Rats via Maintaining Mitochondrial Function and Dynamics in Hippocampal Neurons.

Postoperative cognitive dysfunction (POCD) is characterized by impaired cognitive function, such as decreased learning and memory after anesthesia and surgery. This study aimed to explore the effect of luteoloside, a flavonoid extracted from natural herbs, on sevoflurane-induced cognitive dysfunction. Aged Sprague-Dawley male rats (20 months old) were treated with luteoloside for 7 days prior to sevoflurane exposure. After evaluation using an open field, novel object recognition, and Y-maze tests, it was determined that luteoloside effectively prevented sevoflurane-induced cognitive dysfunction. Sevoflurane exposure led to hippocampal neuron apoptosis in vivo (n = 6) and in vitro (n = 3), while this injury was prevented by luteoloside in a dose-dependent manner. Mechanistically, luteoloside maintained mitochondrial function and dynamics, as evidenced by the restored adenosine triphosphate (ATP) production and mitochondrial membrane potential as well as the upregulated levels of mitochondrial fission (optic atrophy protein 1 (Opa1) and mitofusin1 (Mfn1)) and downregulated mitochondrial fusion (mitochondrial fission 1 (Fisl) and dynamin-related protein 1 (Drp1)) factors. Notably, silencing Opa1 blocked the protective effect of luteoloside on hippocampal neurons and mitochondrial function. In summary, luteoloside prevented sevoflurane-induced cognitive dysfunction in aged rats, which may be achieved by regulating mitochondrial dynamics. Our study reveals the potential of luteoloside in preventing POCD in aged patients.

Impact of Spinal/Epidural Anesthesia Versus General Anesthesia on Perioperative Outcomes in Patients Undergoing Lumbar Spine Surgery: An Updated Systematic Review and Meta-analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: To compare impact of different anesthesia techniques on perioperative outcomes in patients undergoing lumbar spine surgery. SUMMARY OF BACKGROUND DATA: Both general anesthesia and spinal anesthesia/epidural anesthesia can be used for lumbar spine surgery. There is still much controversy that which anesthesia technique is much more suitable for lumbar spine surgery with less complications, general anesthesia or regional anesthesia. METHODS: A comprehensive search of the literature was conducted using Excerpta Medica database (EMBASE), PubMed, and Cochrane library for randomized controlled trials and independent reviewers assessed eligibility for included studies. Primary outcomes included incidences of intraoperative hypertension, hypotension, tachycardia, and bradycardia. Secondary outcomes included postoperative analgesic requirement, postoperative nausea and vomiting (PONV), headache, urinary retention, blood loss, and length of hospital stay. RESULTS: Ten randomized controlled trials consisting of 733 adult patients undergoing lumbar spine surgery were included. Spinal anesthesia/epidural anesthesia group had significant lower incidences of intraoperative hypertension [odds ratio (OR), 0.18; 95% confidence interval (CI), 0.08-0.38; P <0.00001; I2 =0.0%] and tachycardia (OR, 0.45; 95% CI, 0.26-0.79; P =0.006; I2 =0.0%), analgesic requirement in postanesthesia care unit (OR, 0.13; 95% CI, 0.08-0.22; P <0.00001; I2 =0.0%), PONV within 24 hours after surgery (OR, 0.27; 95% CI, 0.16-0.46; P <0.00001; I2 =6.0%), and shorter length of postoperative hospital stay (mean difference, -0.28; 95% CI, -0.37 to -0.18; P <0.00001; I2 =32.0%). There were no significant differences in incidences of intraoperative hypotension and bradycardia, PONV in postanesthesia care unit, analgesic requirement, urinary retention, and headache within 24 hours after surgery. CONCLUSIONS: Low to moderate quality of evidence revealed that patient undergoing lumbar spine surgery might benefit from spinal or epidural anesthesia.

SIRT1 activation attenuates microglia-mediated synaptic engulfment in postoperative cognitive dysfunction.

Background: Postoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current research has focused mainly on microglial activation, but less is known about the resultant neuronal synaptic changes. Recent studies have suggested that Sirtuin-1 (SIRT1) plays a critical role in several different neurological disorders via its involvement in microglial activation. In this study, we evaluate the effects of SIRT1 activation in a POCD mouse model. Materials and methods: Exploratory laparotomy was performed in mice aged 12-14 months under sevoflurane anesthesia to establish our animal POCD model. Transcriptional changes in the hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression was verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, presence of dystrophic neurites, and dendritic spine density were evaluated. Cognitive performance was evaluated using the Y maze and Morris water maze (MWM). Results: Sirtuin-1 expression levels were downregulated in POCD. Exposure to anesthesia and surgery lead to alteration in microglia morphology, increased synaptic engulfment, dendritic spine loss, and cognitive deficits. These effects were alleviated by SRT1720 administration. Conclusion: This study suggests an important neuroprotective role for SIRT1 in POCD pathogenesis. Increasing SIRT1 function represents a promising therapeutic strategy for prevention and treatment of POCD.

Gene Signatures Associated with Temporal Rhythm as Diagnostic Markers of Major Depressive Disorder and Their Role in Immune Infiltration.

Temporal rhythm (TR) is involved in the pathophysiology and treatment response of major depressive disorder (MDD). However, there have been few systematic studies on the relationship between TR-related genes (TRRGs) and MDD. This study aimed to develop a novel prognostic gene signature based on the TRRGs in MDD. We extracted expression information from the Gene Expression Omnibus (GEO) database and retrieved TRRGs from GeneCards. Expressed genes (TRRDEGs) were identified differentially, and their potential biological functions were analyzed. Subsequently, association analysis and receiver operating characteristic (ROC) curves were adopted for the TRRDEGs. Further, upstream transcription factor (TF)/miRNA and potential drugs targeting MDD were predicted. Finally, the CIBERSORT algorithm was used to estimate the proportions of immune cell subsets. We identified six TRRDEGs that were primarily involved in malaria, cardiac muscle contraction, and the calcium-signaling pathway. Four genes (CHGA, CCDC47, ACKR1, and FKBP11) with an AUC of >0.70 were considered TRRDEGs hub genes for ROC curve analysis. Outcomes showed that there were a higher ratio of T cells, gamma-delta T cells, monocytes, and neutrophils, and lower degrees of CD8+ T cells, and memory resting CD4+ T cells in TRRDEGs. Four new TRRDEG signatures with excellent diagnostic performance and a relationship with the immune microenvironment were identified.

Comparison of the Effects of Esketamine/Propofol and Sufentanil/Propofol on the Incidence of Intraoperative Hypoxemia during Bronchoscopy: Protocol for a Randomized, Prospective, Parallel-Group Trial.

BACKGROUND: Propofol, ketamine, and sufentanil are the most commonly used anesthetics during bronchoscopy, alone or in combination, for sedation. Esketamine is an s-enantiomer of ketamine racemate and has both sedative and analgesic effects. Esketamine does not inhibit respiration and maintains hemodynamic stability. This study aims to compare the clinical efficacy of esketamine/propofol with sufentanil/propofol for patients during bronchoscopy. METHODS: Patients undergoing bronchoscopy will be randomly assigned to receive either sufentanil/propofol (sufentanil group; n = 33; sufentanil: 0.2 µg/kg) or esketamine/propofol (esketamine group; n = 33; esketamine: 0.2 mg/kg) for sedation and analgesia. Intraoperative clinical information, general anesthetic drug dosage, the incidence of intraoperative hypoxemia, total time of hypoxemia, awakening time, delirium, nausea and vomiting, adverse reactions, and patient satisfaction will be collected. DISCUSSION: Hypoxia has detrimental effects on patients with respiratory disease. Ameliorating hypoxemia in patients undergoing bronchoscopy is critical. Our results will provide effective sedation with esketamine in patients undergoing bronchoscopy. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR2200058990.

Effect of Etomidate vs Propofol for Total Intravenous Anesthesia on Major Postoperative Complications in Older Patients: A Randomized Clinical Trial.

Importance: Older patients may benefit from the hemodynamic stability of etomidate for general anesthesia. However, it remains uncertain whether the potential for adrenocortical suppression with etomidate may increase morbidity. Objective: To test the primary hypothesis that etomidate vs propofol for anesthesia does not increase in-hospital morbidity after abdominal surgery in older patients. Design, Setting, and Participants: This multicenter, parallel-group, noninferiority randomized clinical trial (Etomidate vs Propofol for In-hospital Complications [EPIC]) was conducted between August 15, 2017, and November 20, 2020, at 22 tertiary hospitals in China. Participants were aged 65 to 80 years and were scheduled for elective abdominal surgery. Patients and outcome assessors were blinded to group allocation. Data analysis followed a modified intention-to-treat principle. Interventions: Patients were randomized 1:1 to receive either etomidate or propofol for general anesthesia by target-controlled infusion. Main Outcomes and Measures: Primary outcome was a composite of major in-hospital postoperative complications (with a noninferiority margin of 3%). Secondary outcomes included intraoperative hemodynamic measurements; postoperative adrenocortical hormone levels; self-reported postoperative pain, nausea, and vomiting; and mortality at postoperative months 6 and 12. Results: A total of 1944 participants were randomized, of whom 1917 (98.6%) completed the trial. Patients were randomized to the etomidate group (n = 967; mean [SD] age, 70.3 [4.0] years; 578 men [59.8%]) or propofol group (n = 950; mean [SD] age, 70.6 [4.2] years; 533 men [56.1%]). The primary end point occurred in 90 of 967 patients (9.3%) in the etomidate group and 83 of 950 patients (8.7%) in the propofol group, which met the noninferiority criterion (risk difference [RD], 0.6%; 95% CI, -1.6% to 2.7%; P = .66). In the etomidate group, mean (SD) cortisol levels were lower at the end of surgery (4.8 [2.7] µg/dL vs 6.1 [3.4] µg/dL; P < .001), and mean (SD) aldosterone levels were lower at the end of surgery (0.13 [0.05] ng/dL vs 0.15 [0.07] ng/dL; P = .02) and on postoperative day 1 (0.14 [0.04] ng/dL vs 0.16 [0.06] ng/dL; P = .001) compared with the propofol group. No difference in mortality was observed between the etomidate and propofol groups at postoperative month 6 (2.2% vs 3.0%; RD, -0.8%; 95% CI, -2.2% to 0.7%) and 12 (3.3% vs 3.9%; RD, -0.6%; 95% CI, -2.3% to 1.0%). More patients had pneumonia in the etomidate group than in the propofol group (2.0% vs 0.3%; RD, 1.7%; 95% CI, 0.7% to 2.8%; P = .001). Results were consistent in the per-protocol population. Conclusions and Relevance: Results of this trial showed that, compared with propofol, etomidate anesthesia did not increase overall major in-hospital morbidity after abdominal surgery in older patients, although it induced transient adrenocortical suppression. Trial Registration: ClinicalTrials.gov Identifier: NCT02910206.