P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy.

Sepsis is defined as a dysregulated host response to infection resulting in life-threatening organ dysfunction. Sepsis-associated encephalopathy (SAE) is the main manifestation of sepsis. Inflammation, peroxidation stress injury, and apoptosis are the main factors involved in the pathogenesis of SAE. A growing body of evidence has proved that P2X7 receptor (P2X7R), a cationic channel receptor that is widely distributed in the body, plays a major role in the occurrence and development of inflammatory injury. Therefore, this review mainly describes the activation of P2X7R in sepsis, which leads to the recruitment of inflammatory cells to the cerebral vasculature, the destruction of the blood-brain barrier, the activation of microglial cells in the brain, the apoptosis of brain cells, and other damage processes. This review also illustrates the potential therapeutic value of P2X7R inhibition in SAE.

The influence of Life's Essential 8 on the link between socioeconomic status and depression in adults: a mediation analysis.

BACKGROUND: Individuals with low socioeconomic status (SES) are at a higher risk of developing depression. However, evidence on the role of cardiovascular health (CVH) in this chain is sparse and limited. The purpose of this research was to assess the mediating role of Life's Essential 8 (LE8), a recently updated measurement of CVH, in the association between SES and depression according to a nationally representative sample of adults. METHODS: Data was drawn from the National Health and Nutrition Examination Survey (NHANES) in 2013-2018. Multivariate logistic regression analysis was applied to analyze the association of SES (measured via the ratio of family income to poverty (FIPR), occupation, educational level, and health insurance) and LE8 with clinically relevant depression (CRD) (evaluated using the Patient Health Questionnaire (PHQ-9)). Multiple linear regression analysis was performed to analyze the correlation between SES and LE8. Mediation analysis was carried out to explore the mediating effect of LE8 on the association between SES and CRD. Moreover, these associations were still analyzed by sex, age, and race. RESULTS: A total of 4745 participants with complete PHQ-9 surveys and values to calculated LE8 and SES were included. In the fully adjusted model, individuals with high SES had a significantly higher risk of CRD (odds ratio = 0.21; 95% confidence interval: 0.136 to 0.325, P < 0.01) compared with those with low SES. Moreover, LE8 was estimated to mediate 22.13% of the total association between SES and CRD, and the mediating effect of LE8 varied in different sex and age groups. However, the mediating effect of LE8 in this chain was significant in different sex, age, and racial subgroups except for Mexican American (MA) individuals. CONCLUSION: The results of our study suggest that LE8 could mediate the association between SES and CRD. Additionally, the mediating effect of LE8 in this chain could be influenced by the race of participants.

Regional ventilation distribution before and after laparoscopic lung parenchymal resection.

Objective.The aim of the present study was to evaluate the influence of one-sided pulmonary nodule and tumour on ventilation distribution pre- and post- partial lung resection.Approach.A total of 40 consecutive patients scheduled for laparoscopic lung parenchymal resection were included. Ventilation distribution was measured with electrical impedance tomography (EIT) in supine and surgery lateral positions 72 h before surgery (T1) and 48 h after extubation (T2). Left lung to global ventilation ratio (Fl), the global inhomogeneity index (GI), standard deviation of regional ventilation delay (RVDSD) and pendelluft amplitude (Apendelluft) were calculated to assess the spatial and temporal ventilation distribution.Main results.After surgery (T2), ventilation at the operated chest sides generally deteriorated compared to T1 as expected. For right-side resection, the differences were significant at both supine and left lateral positions (p< 0.001). The change of RVDSDwas in general more heterogeneous. For left-side resection, RVDSDwas worse at T2 compared to T1 at left lateral position (p= 0.002). The other EIT-based parameters showed no significant differences between the two time points. No significant differences were observed between supine and lateral positions for the same time points respectively.Significance.In the present study, we found that the surgery side influenced the ventilation distribution. When the resection was performed on the right lung, the postoperative ipsilateral ventilation was reduced and the right lung ratio fell significantly. When the resection was on the left lung, the ventilation delay was significantly increased.

Effect of transcutaneous electrical acupoint stimulation on postoperative cognitive function in older patients with lung cancer: A randomized, double-blind, placebo-controlled trial.

Objective: This trial was to examine the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive function in older patients who underwent thoracoscopic pulmonary resection. Methods: This was a prospective, randomized, double-blind, placebo-controlled study. 128 patients scheduled for surgery were randomly assigned to the TEAS group and sham-TEAS group. A standardized intervention of TEAS or sham-TEAS on the acupoints of Baihui (DU20) and bilateral Neiguan (PC6), Hegu (LI4), and Zusanli (ST36) from 30 min before anesthesia induction until the end of the surgery, combined with a general anesthetic protocol performed in the two groups respectively. The primary outcome was the incidence of postoperative cognitive dysfunction (POCD) assessed via the Montreal Cognitive Assessment (MoCA) scale at each time point. The secondary outcomes included the results of the Mini-Mental State Examination (MMSE) score, the Numerical Rating Scale (NRS) on pain and sleep, the European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30), and a chronic pain questionnaire at relative time points. Results: Participants who completed the 12-month trial of the two groups were well-matched in baseline demographic and clinical parameters. At postoperative day 1, day 7, and day 30 time points, the incidence of POCD in the sham-TEAS group was always significantly higher than in the TEAS group (65.4% vs 20%, 43.6% vs 7.3%, 40% vs 3.6%, all P < 0.001). Also, the TEAS group showed better scores of MMSE, sleep, and pain compared with the sham-TEAS group (all P < 0.001). At 6 and 12 months points, the global health scores of the TEAS group were still significantly higher than the sham-TEAS group, and the prevalence of chronic pain was significantly lower than the sham-TEAS group (all P < 0.05). Conclusion: TEAS could effectively improve the postoperative cognitive function and long-term life quality of geriatric patients with lung cancer.

Alterations of the gut microbial community structure modulates the Th17 cells response in a rat model of asphyxial cardiac arrest.

Th17 cells triggered inflammation is a critical element in cerebral ischemic injury, and the gut microbiota intricately impacts T lymphocytes. Nevertheless, it remains unclear whether the gut microbiota involves in cardiac arrest/cardiopulmonary resuscitation (CA/CPR) induced-brain injury through Th17 cells. The present study investigated the interaction between gut microbiota and Th17 cells in a rat model. We observed that CA/CPR induced the alterations of the gut microbial community structure, and elevated the level of IL-17 in the serum, and a slight infiltration of Th17 cells into the brain. The Th17 cells were increased significantly in the peripheral blood, 28.33 ± 6.18% of these Th17 cells were derived from the Peyer's patches of small intestine. Furthermore, fecal microbiota transplantation (FMT) from rats with CA/CPR induced Th17 cell response, promoting hippocampal cell apoptosis and declining learning ability and memory in recipient rats. Taken together, CA/CPR-induced alterations of the gut microbial community structure stimulated Th17 cell response which aggravated brain injury.

Dexmedetomidine Improves Anxiety-like Behaviors in Sleep-Deprived Mice by Inhibiting the p38/MSK1/NFκB Pathway and Reducing Inflammation and Oxidative Stress.

(1) Background: Sleep deprivation (SD) triggers a range of neuroinflammatory responses. Dexmedetomidine can improve sleep deprivation-induced anxiety by reducing neuroinflammatory response but the mechanism is unclear; (2) Methods: The sleep deprivation model was established by using an interference rod device. An open field test and an elevated plus maze test were used to detect the emotional behavior of mice. Mouse cortical tissues were subjected to RNA sequence (RNA-seq) analysis. Western blotting and immunofluorescence were used to detect the expression of p38/p-p38, MSK1/p-MSK1, and NFκBp65/p- NFκBp65. Inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA); (3) Results: SD triggered anxiety-like behaviors in mice and was closely associated with inflammatory responses and the MAPK pathway (as demonstrated by transcriptome analysis). SD led to increased expression levels of p-p38, p-MSK1, and p-NFκB. P38 inhibitor SB203580 was used to confirm the important role of the p38/MSK1/NFκB pathway in SD-induced neuroinflammation. Dexmedetomidine (Dex) effectively improves emotional behavior in sleep-deprived mice by attenuating SD-induced inflammatory responses and oxidative stress in the cerebral cortex, mainly by inhibiting the activation of the p38/MSK1/NFκB pathway; (4) Conclusions: Dex inhibits the activation of the p38/MSK1/NFκB pathway, thus attenuating SD-induced inflammatory responses and oxidative stress in the cerebral cortex of mice.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Transcutaneous Electrical Acupoint Stimulation for Preventing Postoperative Delirium: A Meta-Analysis.

Objective: This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for postoperative delirium (POD) in surgical patients. Methods: Based on database searches of the Wanfang, China National Knowledge Infrastructure (CNKI), VIP, Chinese Biology Medicine (CBM), PubMed, Cochrane Library, and Web of Science, relevant RCTs published before December 30, 2022, were extracted. Outcome indicators included the incidence of POD, changes in Confusion Assessment Method (CAM) scores, Visual Analogue Scale (VAS) scores, and the intraoperative consumption of anesthetics. Data were pooled and analyzed by Review Manager 5.3, and publication bias detection was conducted using Stata 17.0. Results: A meta-analysis containing 715 experimental and 717 control participants from 12 RCTs was performed. The overall results showed that TEAS had obvious superiority with a lower incidence of POD on any day during the postoperative 1 week. In subgroup analyses, the CAM scores on the third postoperative day were significantly lower in the TEAS group than in the control group (MD = -0.52, 95% CI: -1.02 to -0.03, P = 0.04), the VAS scores on the first postoperative day were significantly lower in the TEAS group than in the control group (MD = -0.19, 95% CI: -0.36 to -0.02, P = 0.03), the consumption of propofol and remifentanil were both significantly lower in the TEAS group compared with the control group (MD = -23.1, 95% CI: -37.27 to -8.94, P = 0.001; MD = -105.69, 95% CI: -174.20 to -37.19, P = 0.002). No serious adverse events of TEAS were reported in any of the referenced studies. Conclusion: TEAS has an obvious curative effect in preventing POD and pain in the earlier stage of surgical patients. It could be a promising assisted anesthesia technique in the future.

Tibial fracture surgery in elderly mice caused postoperative neurocognitive disorder via SOX2OT lncRNA in the hippocampus.

Increasing evidence indicates the major role of mitochondrial function in neurodegenerative disease. However, it is unclear whether mitochondrial dynamics directly affect postoperative neurocognitive disorder (PND). This study aimed to analyze the underlying mechanisms of mitochondrial dynamics in the pathogenesis of PND. Tibial fracture surgery was performed in elderly mice to generate a PND model in vivo. Cognitive behavior was evaluated 3 days post-surgery using novel object recognition and fear conditioning. A gradual increase in the SOX2OT mRNA level and decrease in the SOX2 mRNA level were noted, with impaired cognitive function, in the mice 3 days after tibial surgery compared with mice in the sham group. To evaluate the role of SOX2OT in PND, SOX2OT knockdown was performed in vitro and in vivo using lentivirus transfection in HT22 cells and via brain stereotactic injection of lentivirus, respectively. SOX2OT knockdown reduced apoptosis, inhibited oxidative stress, suppressed mitochondrial hyperdivision, attenuated surgery-induced cognitive dysfunction, and promoted downstream SOX2 expression in elderly mice. Furthermore, Sox2 alleviated mitochondrial functional damage by inhibiting the transcription of mitochondrial division protein Drp1. Our study findings indicate that SOX2OT knockout alleviates surgery-induced mitochondrial fission and cognitive function defects by upregulating the expression of Sox2 in mice, resulting in the inhibition of drp1 transcription. Therefore, regulation of the SOX2/Drp1 pathway may be a potential mechanism for the treatment of patients with PND.

The role of periodontitis in the link between alpha-tocopherol intake and cognitive performance: A mediation analysis in older adults.

Background: Epidemiological evidence on alpha (α)-tocopherol intake and cognitive performance in older individuals is controversial and the effect of periodontitis in this chain is sparse and limited. The goal of this study was to characterize the association between α-tocopherol intake and cognitive performance and the mediating role of periodontitis in a nationally representative sample of older adults. Methods: Data from the National Health and Nutrition Examination Survey (NHANES), 2011-2014, were used. Multivariate logistic regression analysis was performed to explore the association of α-tocopherol intake, periodontal measures (mean attachment loss [AL] and mean probing depth [PD]), and clinical periodontitis defined by the European Workshop in Periodontology with poor cognitive performance evaluated by Consortium to Establish a Registry for Alzheimer's disease (CERAD); the animal fluency test (AFT); and the Digit Symbol Substitution test (DSST) and the correlation between α-tocopherol intake and clinical periodontitis. Multiple linear regression analysis was used to explore the relationship between α-tocopherol intake and periodontal measures. Mediation analysis was used to test the effects of periodontal measures on the association between α-tocopherol intake and cognitive measures. Results: A total of 1,749 older participants (≥60 years of age) with complete periodontal diagnosis, dietary retrospective survey, and cognitive tests were included. In the fully adjusted model, the odds ratio (OR) with 95% confidence interval (CI) of CERAD score, AFT score and DSST score were 0.214 (0.137-0.327), 0.378 (0.241-0.585) and 0.298 (0.169-0.512) for the highest versus lowest tertile of α-tocopherol intake, respectively. And participants with clinical periodontitis were more likely to exhibit lower DSST score (OR = 1.689; 95 CI%: 1.018-2.771) than those without periodontitis. Mean AL (OR = 1.296; 95 CI%: 1.102-1.524) and PD (OR = 1.667; 95 CI%: 1.18-2.363) were negatively correlated with DSST, and were estimated to mediate 9.1 and 8.2% of the total association between α-tocopherol intake and cognitive performance, respectively. Conclusion: Finding of the present study suggested that participants with low α-tocopherol intake were at higher risk for developing cognitive decline. Moreover, periodontitis mediated the association between α-tocopherol intake and cognitive performance.

Psychological Distress Was Still Serious Among Anesthesiologists Under the Post COVID-19 Era.

Purpose: This study aims to evaluate the psychological status and the attitudes toward the novel coronavirus disease 2019 (COVID-19) vaccine among anesthesiologists. We expected to analyze related factors and offer them some strategies to prevent and manage psychological issues under the post COVID-19 era. Methods: Based on the Checklist for Reporting Results of Internet E-Surveys (CHERRIES), an online survey was designed and conducted among anesthesiologists in Shaanxi, China. Participants were asked to complete a validated questionnaire voluntarily. The following tests were performed: Depression, Anxiety and Stress Scale (DASS-21), Primary Care Post-traumatic Stress Disorder Screen (PC-PTSD), and the attitudes toward COVID-19 vaccine. Results: A total of 795 anesthesiologists completed the survey, the majority of them were female, young and middle-aged, well educated, and married. The prevalence of depression, anxiety, and stress in this sample were 26.5%, 35.5%, and 19.9%, respectively. Longer daily working time, concomitant basic chronic disease, and COVID-19 exposure were extracted as risk factors for the psychological symptoms, while vaccination, elder age, and married status were negatively associated with them. An unsatisfied vaccination rate (71.9%) which might be linked with inadequate awareness and perception of the COVID-19 vaccine was also detected in this study. Conclusion: Anesthesiologists are still under rising pressure of psychological symptoms in the post COVID-19 era. It is imperative to afford continuous psychological support to them and ensure their mental health and professional performance.

Case report: Post-thoracoscopy pendelluft monitoring.

Asynchronous alveolar ventilation is called pendelluft, which may induce lung injury in spontaneously breathing patients. We report a case that electrical impedance tomography (EIT) was used to assess the pendelluft in a post-thoracoscopy patient. The pendelluft amplitude was as high as 77.5% of the tidal variation. The average regional time shift was 0.5 s. The patient was instructed to adjust the breathing method, symptomatic treatment was performed, and the symptoms were improved. This is the first case reporting pendelluft in a post-thoracoscopy patient. Our case demonstrated that (1) pendelluft may occur in post-thoracoscopy patients and it effects lung function, and (2) early identification of affected patients and implementation of corresponding treatments could improve patient outcomes.

Intraoperative use of low-dose dexmedetomidine for the prevention of emergence agitation following general anaesthesia in elderly patients: a randomized controlled trial.

OBJECTIVE: To clarify the effect of an intraoperative low-dose dexmedetomidine infusion on emergence agitation following general anaesthesia in elderly patients. METHODS: Eighty elderly patients (> 64-years-old) following elective general anaesthesia for radical cancer surgeries were randomly allocated into two groups (n = 40 each): the dexmedetomidine group (Group D) and the normal saline group (Group C). Anaesthesia was maintained with continuous intravenous infusion of dexmedetomidine at - 0.2 µg kg-1 h-1 in Group D, and an equal volume of normal saline (0.5 ml kg-1 h-1) was given in Group C. All patients were observed for 30 min in the post-anaesthesia care unit (PACU), AFPS and NRS were recorded every 2 min, and the total doses of nalbuphine and fentanyl were calculated in the PACU. MAP and HR were recorded at the time of 10 min (T1), 20 min (T2), 30 min (T3) after dexmedetomidine or saline pumping, and before extubation (T4), immediately after extubation (T5), and 5 min after extubation (T6). We also documented some durations, including anaesthesia duration (D1), surgery duration (D2), duration from the end of surgery to extubation (D3), and emergence agitation duration (D4). RESULTS: The MAP in Group C was significantly higher than that in Group D (P < 0.05), and there were no significant changes between the two groups in HR and MAP within each time point and D1, D2, D3, and D4. The incidence of agitation, NRS score and total dose of nalbuphine and fentanyl were all lower in Group D than in Group C (P < 0.05). CONCLUSION: An intraoperative low-dose dexmedetomidine continuous infusion can reduce emergence agitation following general anaesthesia in elderly patients (> 64-years-old), remain stable in terms of haemodynamics, and not lead to delays in anaesthesia recovery time and extubation time.

LMA® protector™ in patients undergoing laparoscopic surgeries: a multicenter prospective observational study.

BACKGROUND: Laryngeal masks airway (LMA) has been increasingly used in surgical patients. However, the use of LMA in laparoscopic surgeries remains controversial. The major concerns include the potential risk of esophageal regurgitation, aspiration, and difficulties to achieve effective ventilation. The aim of this study was to evaluate the safety and effectiveness of the LMA® Protector™ in patients undergoing laparoscopic surgery. METHODS: Patients aged 18 to 70 years, scheduled for laparoscopic surgeries were included. The insertion time, successful insertion rate, and oropharyngeal leak pressure were measured. Airway complications and airway manipulations during the procedure were documented. Effective ventilation rate was calculated. Visible bloodstains and reflux content in the drainage channel were documented after the removal of LMA® Protector™. RESULTS: Three hundred patients were enrolled. The insertion of LMA® Protector™ failed in seven patients resulting with a successful insertion rate of 97.7%. During the maintenance of anesthesia, airway manipulation was required in 19 patients (19/293, 6.48%), in three of whom the LMA was replaced with endotracheal intubation resulting with an effective ventilation rate of 96.7% (290/300). The oropharyngeal leak pressure was 30.18 ± 5.88 cmH2O. Seventy-five patients (25.86%) reported mild sore throat on the first day after surgery. Bloodstains on study devices were noticed in 58 patients (20%). Seventy-five patients (25.86%) reported mild sore throat on the first day after surgery. Gastric reflux was noticed in the drainage tube in 5 patients (1.72%) with no signs of aspiration in any of those patients. CONCLUSIONS: The LMA® Protector™ was shown to be safe and effective in patients undergoing laparoscopic surgeries. Although minor complications that require no further treatment, no clinically diagnosed aspiration was noticed in our study. Gastric reflux was noticed in the drainage tube in five patients undergoing laparoscopic gynecology surgery. Further research is needed to verify whether LMA® Protector™ is suitable for procedures in Trendelenburg position or other situations that a high risk of gastroesophageal reflux exists. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry ( ChiCTR1800018300 , date of registration: September 2018).

Transcutaneous electrical acupoint stimulation before surgery reduces chronic pain after mastectomy: A randomized clinical trial.

STUDY OBJECTIVE: Despite multiple interventions, the incidence of chronic pain after mastectomy could be as high as 50% after surgery. This study aimed to determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) before anesthesia induction in reducing chronic pain and to compare the effect of combined acupoint TEAS with that of single acupoint TEAS. DESIGN: A multicenter randomized clinical trial. SETTING: The study was conducted at six medical centers in China from May 2016 to April 2018. Final follow-up was on October 26, 2018. PARTICIPANTS: Eligible patients were women scheduled for radical mastectomy under general anesthesia. INTERVENTIONS: Patients were randomly and equally grouped into sham control (n = 188), single acupoint (PC6, n = 198), or combined acupoints (PC6 and CV17, n = 190) TEAS groups using a centralized computer-generated randomization system. TEAS was applied for 30 min before anesthesia induction. The sham-operated control group received electrode attachment but without stimulation. Anesthesiologists, surgeons, and outcome assessors were blinded to the interventions. MEASURES: The primary endpoint was the incidence of chronic pain 6 months after surgery. Incidences were compared among the groups using the unadjusted χ2 test. RESULTS: Of the 576 randomized patients, 568 completed the trial. In the intention-to-treat analysis, post-mastectomy pain at 6 months was reported in 42 of 190 patients (22.1%) in the combined acupoints group, 65 of 188 patients (34.6%) in the sham-operated group (P = 0.007; relative risk [RR], 95% confidence interval [CI]: 0.68, 0.52-0.89), and 72 of 198 patients (36.4%) in the single acupoint group (P = 0.002; RR, 95% CI: 0.72, 0.55-0.93). Remifentanil consumption during surgery and postoperative nausea and vomiting at 24 h after surgery were lower in the combined acupoint group than that in the sham-operated group. CONCLUSION: TEAS at combined acupoints before surgery was associated with reduced chronic pain 6 months after surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02741726. Registered on April 13, 2016.

Isoflurane preconditioning effects on brain damage induced by electromagnetic pulse radiation through epigenetic modification of BDNF gene transcription.

BACKGROUND: The effects of electromagnetic pulse (EMP) radiation on cognitive impairment have attracted much attention, but the mechanism is still unclear. Regulation of brain-derived neurotrophic factor (BDNF) gene expression has been found to promote memory formation and neuronal survival. Isoflurane preconditioning (IP) was reported to have a neuroprotective effect. In this study, we verified the protective effect of IP against brain injury induced by EMP exposure and examined the relation of this effect with BDNF gene regulation. METHODS: Twenty-four hours before EMP exposure, rats were pretreated with 2% inhaled isoflurane for 30 minutes. At 24 hours after EMP injury, the Morris water maze test was carried out. Meanwhile, the other rats were executed and their brain tissues were used for Nissl staining, qRT-PCR, western blot and chromatin immunoprecipitation. RESULTS: The Morris water maze results showed that 2% IP improved the spatial learning and memory ability of the rats. The Nissl staining results showed 2% of IP alleviated neuronal damage. Also, we detected the mRNA and protein expression of BDNF, and 2% IP significantly increased the expression of BDNF. We also found the expression level of histone deacetylase 2 (HDAC2) was increased and that EMP exposure significantly decreased H3 acetylation, while 2% IP reversed these phenomena, individually, BDNF transcription was activated, and neurogenesis after EMP exposure was alleviated. CONCLUSIONS: Our results suggested that 2% of IP alleviates cognitive impairment induced by EMP exposure in rats. Also, the sustained elevated level of BDNF gene transcription may be an essential mechanism for stimulating neurogenesis because of the increased level of HDAC2-dependent H3 acetylation.

The efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy: a multicentered, randomized, positive-controlled, phase III clinical trial.

This study aimed to evaluate the efficacy and safety of remimazolam tosylate versus propofol in patients undergoing colonoscopy. In this multicentered, blinded, randomized, active-controlled, non-inferior phase III trial, 384 eligible patients who were about to undergo colonoscopy were randomized as a ratio of 1:1 into remimazolam and propofol group. Procedure success was assessed and defined as the completion of colonoscopy without administration of rescue sedative agent or more than 5 top-ups of trial drug in any 15 minute-period after initial administration of trial drug. Sedation quality was evaluated by Modified Observer's Assessment of Alertness/Sedation score. Treatment-emergent adverse events were recorded. Procedure success rate was 96.91% (188/194) in remimazolam group and 100% (190/190) in propofol group, and the difference in rate was -3.09% with 95% confidence interval (CI) of -5.53%~-0.66%. Since the lower limit of 95% CI was greater than the non-inferiority margin of -8.00%, the efficacy of remimazolam tosylate was non-inferior to propofol. Besides, induction time of sedation was increased (P<0.001), while hypotension and respiratory depression was decreased in remimazolam group compared to propofol group; however, time to fully alert (P>0.05) or time to discharge (P>0.05) were unchanged. For safety assessment, total treatment-emergent adverse events were decreased in remimazolam group compared to propofol group (P<0.001); specifically, administration site pain (P<0.001), increased bilirubin (P=0.019), decreased respiratory rate (P<0.001) and decreased SpO2 (P<0.001) were less frequent in remimazolam group compared with propofol group. In conclusion, remimazolam tosylate is non-inferior in sedation efficacy while safer than propofol in patients undergoing colonoscopy.

Irisin Protects Brain against Ischemia/Reperfusion Injury through Suppressing TLR4/MyD88 Pathway.

BACKGROUND: Inflammatory response exerts an important role in ischemia/reperfusion (I/R) injury. TLR4 and myeloid differentiation factor 88 (MyD88) are key components in inflammation and are involved in the cerebral I/R injury. Irisin is a skeletal muscle-derived myokine produced after exercise, which was found to suppress inflammation. In this study, we investigated whether irisin could protect the brain from I/R injury through the TLR4/MyD88 pathway. METHODS: Male Sprague Dawley rats (20 months, 190 ∼ 240 g) were pretreated with irisin at 10, 50, or 100 mg/kg for consecutive 3 days and then subjected to surgery of middle cerebral artery occlusion or sham operation. Infarct size and neuron loss were measured to evaluate brain damage. The mRNA and protein levels of TLR4 and MyD88 were measured by in situ hybridization and immunohistochemistry, respectively. NF-κB activation was assessed by electrophoretic mobility shift assay. Neurological function was evaluated by neurobehavior score test and passive avoidance test. RESULTS: Irisin could reduce neuronal damage and neurofunctional impairment after I/R injury. This effect was mediated by downregulating the TLR4/MyD88 and inhibiting NF-κB activation. CONCLUSION: Irisin plays a beneficial effect in I/R injury through regulating the TLR4/MyD88 pathway.