Complement C3 From Astrocytes Plays Significant Roles in Sustained Activation of Microglia and Cognitive Dysfunctions Triggered by Systemic Inflammation After Laparotomy in Adult Male Mice.

Aberrant activation of complement cascades plays an important role in the progress of neurological disorders. Complement C3, the central complement component, has been implicated in synaptic loss and cognitive impairment. Recent study has shown that wound injury-induced systemic inflammation can trigger the increase of C3 in the brain. Our previous studies have demonstrated that laparotomy-triggered systemic inflammation could induce neuroinflammation and cognitive dysfunctions. Furthermore, sustained activation of microglia was observed even 14 days after laparotomy, while most of cytokines had returned to basal levels rapidly at the earlier time point. Although we have demonstrated that anti-inflammatory intervention successfully attenuated cognitive dysfunction by preventing increase of cytokines and activation of microglia, how sustained activation of microglia and cognitive dysfunction occur is still a mystery. In this study, we investigated the role of C3 in mediating activation of microglia and cognitive dysfunction by using laparotomy in adult male mouse only as the experimental model of systemic inflammation and AAV9-C3shRNA. Our data observed that laparotomy induced neurotoxic reactive astrocytes with an increase of C3 in the hippocampus. Furthermore, inhibition of C3 by AAV9-C3shRNA prevented synaptic engulfment by microglia and attenuated cognitive dysfunctions after laparotomy. Inhibition of C3 did not modulate activation of astrocytes and expression of various cytokines. Current findings demonstrated that C3 plays significant roles in sustained activation of microglia and cognitive dysfunctions, which suggests that C3 is the valuable molecule target to attenuate in neurological conditions characterised by neuroinflammation and cognitive dysfunction.

Downregulation of the glucose transporter GLUT 1 in the cerebral microvasculature contributes to postoperative neurocognitive disorders in aged mice.

INTRODUCTION: Glucose transporter 1 (GLUT1) is essential for glucose transport into the brain and is predominantly expressed in the cerebral microvasculature. Downregulation of GLUT1 precedes the development of cognitive impairment in neurodegenerative conditions. Surgical trauma induces blood-brain barrier (BBB) disruption, neuroinflammation, neuronal mitochondria dysfunction, and acute cognitive impairment. We hypothesized that surgery reduces the expression of GLUT1 in the BBB that in turn disrupts its integrity and contributes to metabolic dysregulation in the brain that culminates in postoperative cognitive impairment. METHODOLOGY: Using an abdominal surgery model in aged WT mice, we assessed the perioperative changes in cognitive performance, tight junction proteins expression, GLUT1 expression, and the associated metabolic effects in the hippocampus. Thereafter, we evaluated the effects of these parameters in aged mice with conditional overexpression of GLUT1, and then again in aged mice with conditional overexpression of GLUT1 with or without prior exposure to the GLUT1 inhibitor ST-31. RESULTS: We showed a significant decline in cognitive performance, along with GLUT1 reduction and diminished glucose metabolism, especially in the ATP level in the postoperative mice compared with controls. Overexpression of GLUT1 expression alleviated postoperative cognitive decline and improved metabolic profiles, especially in adenosine, but did not directly restore ATP generation to control levels. GLUT1 inhibition ameliorated the postoperative beneficial effects of GLUT1 overexpression. CONCLUSIONS: Surgery-induced GLUT1 reduction significantly contributes to postoperative cognitive deficits in aged mice by affecting glucose metabolism in the brain. It indicates the potential of targeting GLUT1 to ameliorate perioperative neurocognitive disorders.

ChatGPT versus human in generating medical graduate exam multiple choice questions-A multinational prospective study (Hong Kong S.A.R., Singapore, Ireland, and the United Kingdom).

INTRODUCTION: Large language models, in particular ChatGPT, have showcased remarkable language processing capabilities. Given the substantial workload of university medical staff, this study aims to assess the quality of multiple-choice questions (MCQs) produced by ChatGPT for use in graduate medical examinations, compared to questions written by university professoriate staffs based on standard medical textbooks. METHODS: 50 MCQs were generated by ChatGPT with reference to two standard undergraduate medical textbooks (Harrison's, and Bailey & Love's). Another 50 MCQs were drafted by two university professoriate staff using the same medical textbooks. All 100 MCQ were individually numbered, randomized and sent to five independent international assessors for MCQ quality assessment using a standardized assessment score on five assessment domains, namely, appropriateness of the question, clarity and specificity, relevance, discriminative power of alternatives, and suitability for medical graduate examination. RESULTS: The total time required for ChatGPT to create the 50 questions was 20 minutes 25 seconds, while it took two human examiners a total of 211 minutes 33 seconds to draft the 50 questions. When a comparison of the mean score was made between the questions constructed by A.I. with those drafted by humans, only in the relevance domain that the A.I. was inferior to humans (A.I.: 7.56 +/- 0.94 vs human: 7.88 +/- 0.52; p = 0.04). There was no significant difference in question quality between questions drafted by A.I. versus humans, in the total assessment score as well as in other domains. Questions generated by A.I. yielded a wider range of scores, while those created by humans were consistent and within a narrower range. CONCLUSION: ChatGPT has the potential to generate comparable-quality MCQs for medical graduate examinations within a significantly shorter time.

ST36 acupoint injection with anisodamine for postoperative nausea and vomiting in female patients after bariatric surgery: a prospective, randomized controlled trial.

BACKGROUND: The use of multimodal pharmacological prophylactic regimes has decreased postoperative nausea and vomiting (PONV) in general but it still occurs in over 60% of female patients after bariatric surgery. This study aimed to evaluate the efficacy of ST36 acupoint injection with anisodamine in prevention of PONV among female patients after bariatric surgery. METHODS: Ninety patients undergoing laparoscopic sleeve gastrectomy were randomly allocated to anisodamine or control group at the ratio of 2:1. Anisodamine or normal saline was injected into Zusanli (ST36) bilaterally after induction of general anesthesia. The incidence and severity of PONV were assessed during the first 3 postoperative days and at 3 months. The quality of early recovery of anesthesia, gastrointestinal function, sleep quality, anxiety, depression, and complications were also evaluated. RESULTS: Baseline and perioperative characteristics were comparable between two groups. In the anisodamine group, 25 patients (42.4%) experienced vomiting within postoperative 24 h compared with 21 (72.4%) in the control group (relative risk 0.59; 95% confidence interval 0.40-0.85). Time to first rescue antiemetic was 6.5 h in anisodamine group, and 1.7 h in the control group (P = 0.011). Less rescue antiemetic was required during the first 24 h in the anisodamine group (P = 0.024). There were no differences in either postoperative nausea or other recovery characteristics. CONCLUSIONS: The addition of ST36 acupoint injection with anisodamine significantly reduced postoperative vomiting without affecting nausea in female patients with obesity undergoing laparoscopic sleeve gastrectomy.

The role of PKC/PKR in aging, Alzheimer's disease, and perioperative neurocognitive disorders.

Background: The incidence of perioperative neurocognitive disorders (PNDs) is reportedly higher in older patients. Mitochondrial and synaptic dysfunctions have consistently been demonstrated in models of aging and neurodegenerative diseases; nonetheless, their role in PND is not well understood. Methods: The Morris water maze and elevated plus maze tests were used to assess the learning and memory abilities of both C57BL/6 and 3×Tg-AD mice of different ages (8 and 18 months). PND was induced by laparotomy in C57BL/6 mice and 3×Tg-AD mice (8 months old). Markers associated with neuroinflammation, mitochondrial function, synaptic function, and autophagy were assessed postoperatively. The roles of protein kinase C (PKC) and double-stranded RNA-dependent protein kinase (PKR) were further demonstrated by using PKC-sensitive inhibitor bisindolylmaleimide X (BIMX) or PKR-/- mice. Results: Significant cognitive impairment was accompanied by mitochondrial dysfunction and autophagy inactivation in both aged C57BL/6 and 3×Tg-AD mice. Laparotomy induced a significant neuroinflammatory response and synaptic protein loss in the hippocampus. Cognitive and neuropathological changes induced by aging or laparotomy were further exacerbated in 3×Tg-AD mice. Deficits in postoperative cognition, hippocampal mitochondria, autophagy, and synapse were significantly attenuated after pharmacological inhibition of PKC or genetic deletion of PKR. Conclusions: Our findings suggest similar pathogenic features in aging, Alzheimer's disease, and PND, including altered mitochondrial homeostasis and autophagy dysregulation. In addition, laparotomy may exacerbate cognitive deficits associated with distinct neuronal inflammation, mitochondrial dysfunction, and neuronal loss independent of genetic background. The dysregulation of PKC/PKR activity may participate in the pathogenesis of these neurodegenerative diseases.

Leukocyte invasion of the brain after peripheral trauma in zebrafish (Danio rerio).

Despite well-known systemic immune reactions in peripheral trauma, little is known about their roles in posttraumatic neurological disorders, such as anxiety, sickness, and cognitive impairment. Leukocyte invasion of the brain, a common denominator of systemic inflammation, is involved in neurological disorders that occur in peripheral inflammatory diseases, whereas the influences of peripheral leukocytes on the brain after peripheral trauma remain largely unclear. In this study, we found that leukocytes, largely macrophages, transiently invaded the brain of zebrafish larvae after peripheral trauma through vasculature-independent migration, which was a part of the systemic inflammation and was mediated by interleukin-1b (il1b). Notably, myeloid cells in the brain that consist of microglia and invading macrophages were implicated in posttraumatic anxiety-like behaviors, such as hyperactivity (restlessness) and thigmotaxis (avoidance), while a reduction in systemic inflammation or myeloid cells can rescue these behaviors. In addition, invading leukocytes together with microglia were found to be responsible for the clearance of apoptotic cells in the brain; however, they also removed the nonapoptotic cells, which suggested that phagocytes have dual roles in the brain after peripheral trauma. More importantly, a category of conserved proteins between zebrafish and humans or rodents that has been featured in systemic inflammation and neurological disorders was determined in the zebrafish brain after peripheral trauma, which supported that zebrafish is a translational model of posttraumatic neurological disorders. These findings depicted leukocyte invasion of the brain during systemic inflammation after peripheral trauma and its influences on the brain through il1b-dependent mechanisms.

Prehabilitative resistance exercise reduces neuroinflammation and improves mitochondrial health in aged mice with perioperative neurocognitive disorders.

BACKGROUND: Postoperative neurocognitive dysfunction remains a significant problem in vulnerable groups such as the elderly. While experimental data regarding its possible pathogenic mechanisms accumulate, therapeutic options for this disorder are limited. In this study, we evaluated the neuroprotective effect of a period of preconditioning resistant training on aged mice undergoing abdominal surgery. Further, we examined the underlying mechanisms from the perspective of neuroinflammatory state and synaptic plasticity in the hippocampus. METHODS: 18-month-old C57BL/6N mice were trained for 5 weeks using a ladder-climbing protocol with progressively increasing weight loading. Preoperative baseline body parameters, cognitive performance and neuroinflammatory states were assessed and compared between sedentary and trained groups of 9-month-old and 18-month-old mice. To access the neuroprotective effect of resistance training on postoperative aged mice, both sedentary and trained mice were subjected to a laparotomy under 3% sevoflurane anesthesia. Cognitive performance on postoperative day 14, hippocampal neuroinflammation, mitochondrial dysfunction and synaptic plasticity were examined and compared during groups. RESULTS: 18-month-old mice have increased body weight, higher peripheral and central inflammatory status, reduction in muscle strength and cognitive performance compared with middle-aged 9-month-old mice, which were improved by resistance exercise. In the laparotomy group, prehabilitative resistant exercise improved cognitive performance and synaptic plasticity, reduced inflammatory factors and glial cells activation after surgery. Furthermore, resistance exercise activated hippocampal PGC-1α/BDNF/Akt/GSK-3ß signaling and improved mitochondrial biogenesis, as well as ameliorated mitochondrial dynamics in postoperative-aged mice. CONCLUSIONS: Resistance exercise reduced risk factors for perioperative neurocognitive disorders such as increased body weight, elevated inflammatory markers, and pre-existing cognitive impairment. Accordantly, preoperative resistance exercise improved surgery-induced adverse effects including cognitive impairment, synaptic deficit and neuroinflammation, possibly by facilitate mitochondrial health through the PGC1-a/BDNF pathway.

Sevoflurane Induces Neurotoxicity in the Animal Model with Alzheimer's Disease Neuropathology via Modulating Glutamate Transporter and Neuronal Apoptosis.

Perioperative neurocognitive disorders are frequently observed in postoperative patients and previous reports have shown that pre-existing mild cognitive impairment with accumulated neuropathology may be a risk factor. Sevoflurane is a general anesthetic agent which is commonly used in clinical practice. However, the effects of sevoflurane in postoperative subjects are still controversial, as both neurotoxic or neuroprotective effects were reported. The purpose of this study is to investigate the effects of sevoflurane in 3 × Tg mice, a specific animal model with pre-existing Alzheimer's disease neuropathology. 3 × Tg mice and wild-type mice were exposed to 2 h of sevoflurane respectively. Cognitive function, glutamate transporter expression, MAPK kinase pathways, and neuronal apoptosis were accessed on day 7 post-exposure. Our findings indicate that sevoflurane-induced cognitive deterioration in 3 × Tg mice, which was accompanied with the modulation of glutamate transporter, MAPK signaling, and neuronal apoptosis in the cortical and hippocampal regions. Meanwhile, no significant impact was observed in wild-type mice. Our results demonstrated that prolonged inhaled sevoflurane results in the exacerbation of neuronal and cognitive dysfunction which depends on the neuropathology background.

Sigesbeckia orientalis L. Derived Active Fraction Ameliorates Perioperative Neurocognitive Disorders Through Alleviating Hippocampal Neuroinflammation.

Neuroinflammation is closely related to the pathogenesis of perioperative neurocognitive disorders (PNDs), which is characterized by the activation of microglia, inflammatory pathways and the release of inflammatory mediators. Sigesbeckia orientalis L. (SO) is a traditional Chinese medicine which demonstrates anti-inflammatory activities in different models. In this study, we aim to isolate the active fraction from the extract of SO with higher anti-inflammatory potential and confirm if the selected fraction exerts neuroprotection against the development of PND in an animal model. Moreover, the components in the selected fraction would be determined by UPLC-PDA analysis. Three fractions were prepared by column chromatography packed with three different macroporous resins. Anti-inflammatory activities of prepared fractions were accessed in microglial BV2 cultures by nitric oxide release, gene expression of inflammatory cytokines and activation of inflammatory JNK and NF-kB pathway molecules. Our results demonstrated that the fraction prepared from D101 macroporous resin (D101 fraction) exhibited a more potent anti-neuroinflammatory effect. The neuroprotective effect of D101 fraction was further examined in postoperative mice. Our results showed that surgery-induced cognitive dysfunction was attenuated by the D101 fraction treatment. This fraction also reduced microglial activation, inflammatory cytokines and inhibiting JNK and NF-kB pathway molecules in the hippocampus. In addition, surgery induced dendritic spine loss while D101 fraction ameliorated the spine loss in the hippocampus. For safety concerns, anti-thrombotic effect was examined by tail bleeding assay and no significant change of the bleeding pattern was found. UPLC-PDA analysis indicated that flavonoids (rutin, isochlorogenic acid A, isochlorogenic acid C) and terpenoid (darutoside) were the most important components in the D101 fraction. Our results support a therapeutic, as well as the translational potential for D101 fraction in ameliorating postoperative neuroinflammation and subsequent PND in the clinical setting without increasing bleeding tendencies.

Identifying and articulating the student experience in the Intercalated Enrichment Year.

BACKGROUND: Benefits of intercalation during an undergraduate medical degree are well-recognized. The University of Hong Kong implemented a compulsory Enrichment Year (EY) in its Bachelor of Medicine and Bachelor of Surgery degree programme (MBBS) in 2016. In their third year of study, students could work on an area of interest in any of three programme categories (i) intercalation/ university exchange (IC); (ii) research (RA); (iii) service/ humanitarian work (SH). This study aimed to explore the barriers, enablers, and overall student learning experiences from the first cohort of EY students in order to inform future development of the EY. METHODS: An exploratory sequential mixed-method study in 2019-20. Twenty students were purposively selected to attend three semi-structured focus group interviews. Conventional thematic analysis was employed and results assisted the design of a cross-sectional questionnaire. Sixty-three students completed the questionnaire. ANOVA or chi-square test was used to compare the difference in student's characteristics, barriers, enablers and perspectives on EY between programme categories. Adjusting student's characteristics, logistic regressions were conducted to identify the effect of programme categories on the EY experience. RESULTS: Most students (95% in the questionnaire) agreed that EY was worthwhile and more rewarding than expected. EY was positively regarded for enhancing personal growth and interpersonal relationships. The main barriers were financial difficulties, scholarship issues and insufficient information beforehand. A few students had practical (i.e. accommodation, cultural adaptation) problems. Potential enablers included better financial support, more efficient information exchange and fewer assignments and preparation tasks. Similar barriers were encountered by students across all three categories of EY activities. CONCLUSIONS: Personal growth was the most important benefit of the EY. Barriers were consistent with those identified in the literature except for cultural adaptation, which could be related to Hong Kong's unique historical context. Financial limitation was the most concerning barrier, as it could result in unequal access to educational opportunities. Better and timely access to scholarships and other funding sources need to be considered. TRIAL REGISTRATION: Ethics approval was obtained from the local Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 19-585 ).

Cerebral Glutamate Regulation and Receptor Changes in Perioperative Neuroinflammation and Cognitive Dysfunction.

Glutamate is the major excitatory neurotransmitter in the central nervous system and is intricately linked to learning and memory. Its activity depends on the expression of AMPA and NMDA receptors and excitatory amino transporters on neurons and glial cells. Glutamate transporters prevent the excess accumulation of glutamate in synapses, which can lead to aberrant synaptic signaling, excitotoxicity, or cell death. Neuroinflammation can occur acutely after surgical trauma and contributes to the development of perioperative neurocognitive disorders, which are characterized by impairment in multiple cognitive domains. In this review, we aim to examine how glutamate handling and glutamatergic function are affected by neuroinflammation and their contribution to cognitive impairment. We will first summarize the current data regarding glutamate in neurotransmission, its receptors, and their regulation and trafficking. We will then examine the impact of inflammation on glutamate handling and neurotransmission, focusing on changes in glial cells and the effect of cytokines. Finally, we will discuss these changes in the context of perioperative neuroinflammation and the implications they have for perioperative neurocognitive disorders.

The Complement System in the Central Nervous System: From Neurodevelopment to Neurodegeneration.

The functions of the complement system to both innate and adaptive immunity through opsonization, cell lysis, and inflammatory activities are well known. In contrast, the role of complement in the central nervous system (CNS) which extends beyond immunity, is only beginning to be recognized as important to neurodevelopment and neurodegeneration. In addition to protecting the brain against invasive pathogens, appropriate activation of the complement system is pivotal to the maintenance of normal brain function. Moreover, overactivation or dysregulation may cause synaptic dysfunction and promote excessive pro-inflammatory responses. Recent studies have provided insights into the various responses of complement components in different neurological diseases and the regulatory mechanisms involved in their pathophysiology, as well as a glimpse into targeting complement factors as a potential therapeutic modality. However, there remain significant knowledge gaps in the relationship between the complement system and different brain disorders. This review summarizes recent key findings regarding the role of different components of the complement system in health and pathology of the CNS and discusses the therapeutic potential of anti-complement strategies for the treatment of neurodegenerative conditions.

A flipped classroom, same-level peer-assisted learning approach to clinical skill teaching for medical students.

BACKGROUND: Clinical procedural skills are vital components of medical education. Increased student intake and limited capacity of medical schools necessitate more efficient ways to deliver clinical skill teaching. This study employed a flipped classroom, peer-assisted learning approach to deliver clinical skill teaching. It aimed to determine the influence of pre-class demonstration video watching and in-class student-student interactions on clinical skill acquisition. METHODS: In 2017, a cohort of 205 medical students in their penultimate year of undergraduate medical study were recruited, and they learned bag mask ventilation and intravenous cannulation during this study. The participants watched a demonstration video before class, and then underwent self-directed practice as triads. Afterwards, each participant video-recorded their skill performance and completed post-class questionnaires. The videos were evaluated by two blinded assessors. RESULTS: A hundred and thirty-one participants (63.9%) completed the questionnaire. For bag mask ventilation, participants who claimed to have watched the corresponding demonstration video before class achieved higher performance scores (those who watched before class: 7.8 ± 1.0; those who did not: 6.3 ± 1.7; p < 0.01). For intravenous cannulation, while there is no significant difference in performance scores (those who watched before class: 14.3 ± 1.3; those who did not: 14.1 ± 1.4; p = 0.295), those who watched the video before class received less interventions from their peers during triad practice (those who watched before class: 2.9 ± 1.8; those who did not: 4.3 ± 2.9; p < 0.05). The questionnaire results showed that most participants preferred the new approach of clinical skill teaching and perceived it to be useful for skill acquisition. CONCLUSION: The flipped classroom, same-level peer-assisted learning model is potentially an effective way to address the current challenges and improve the efficiency of clinical procedural skill teaching in medical schools.

Effect of Intraoperative Dexmedetomidine on Recovery of Gastrointestinal Function After Abdominal Surgery in Older Adults: A Randomized Clinical Trial.

Importance: Postoperative ileus is common after abdominal surgery, and small clinical studies have reported that intraoperative administration of dexmedetomidine may be associated with improvements in postoperative gastrointestinal function. However, findings have been inconsistent and study samples have been small. Further examination of the effects of intraoperative dexmedetomidine on postoperative gastrointestinal function is needed. Objective: To evaluate the effects of intraoperative intravenous dexmedetomidine vs placebo on postoperative gastrointestinal function among older patients undergoing abdominal surgery. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at the First Affiliated Hospital of Anhui Medical University in Hefei, China (lead site), and 12 other tertiary hospitals in Anhui Province, China. A total of 808 participants aged 60 years or older who were scheduled to receive abdominal surgery with an expected surgical duration of 1 to 6 hours were enrolled. The study was conducted from August 21, 2018, to December 9, 2019. Interventions: Dexmedetomidine infusion (a loading dose of 0.5 µg/kg over 15 minutes followed by a maintenance dose of 0.2 µg/kg per hour) or placebo infusion (normal saline) during surgery. Main Outcomes and Measures: The primary outcome was time to first flatus. Secondary outcomes were postoperative gastrointestinal function measured by the I-FEED (intake, feeling nauseated, emesis, physical examination, and duration of symptoms) scoring system, time to first feces, time to first oral feeding, incidence of delirium, pain scores, sleep quality, postoperative nausea and vomiting, hospital costs, and hospital length of stay. Results: Among 808 patients enrolled, 404 were randomized to receive intraoperative dexmedetomidine, and 404 were randomized to receive placebo. In total, 133 patients (60 in the dexmedetomidine group and 73 in the placebo group) were excluded because of protocol deviations, and 675 patients (344 in the dexmedetomidine group and 331 in the placebo group; mean [SD] age, 70.2 [6.1] years; 445 men [65.9%]) were included in the per-protocol analysis. The dexmedetomidine group had a significantly shorter time to first flatus (median, 65 hours [IQR, 48-78 hours] vs 78 hours [62-93 hours], respectively; P < .001), time to first feces (median, 85 hours [IQR, 68-115 hours] vs 98 hours [IQR, 74-121 hours]; P = .001), and hospital length of stay (median, 13 days [IQR, 10-17 days] vs 15 days [IQR, 11-18 days]; P = .005) than the control group. Postoperative gastrointestinal function (as measured by the I-FEED score) and delirium incidence were similar in the dexmedetomidine and control groups (eg, 248 patients [72.1%] vs 254 patients [76.7%], respectively, had I-FEED scores indicating normal postoperative gastrointestinal function; 18 patients [5.2%] vs 12 patients [3.6%] had delirium on postoperative day 3). Conclusions and Relevance: In this randomized clinical trial, the administration of intraoperative dexmedetomidine reduced the time to first flatus, time to first feces, and length of stay after abdominal surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative recovery of gastrointestinal function among older adults. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800017232.

Is exercise a senolytic medicine? A systematic review.

Cellular senescence, a state of irreversible growth arrest triggered by various stressors, engages in a category of pathological processes, whereby senescent cells accumulate in mitotic tissues. Senolytics as novel medicine against aging and various diseases through the elimination of senescent cells has emerged rapidly in recent years. Exercise is a potent anti-aging and anti-chronic disease medicine, which has shown the capacity to lower the markers of cellular senescence over the past decade. However, whether exercise is a senolytic medicine for aging and various diseases remains unclear. Here, we have conducted a systematic review of the published literature studying the senolytic effects of exercise or physical activity on senescent cells under various states in both human and animal models. Exercise can reduce the markers of senescent cells in healthy humans, while it lowered the markers of senescent cells in obese but not healthy animals. The discrepancy between human and animal studies may be due to the relatively small volume of research and the variations in markers of senescent cells, types of cells/tissues, and health conditions. These findings suggest that exercise has senolytic properties under certain conditions, which warrant further investigations.

Effects of Epidural Anesthesia on Quality of Life in Elderly Patients Undergoing Esophagectomy.

Continuous epidural analgesia during surgery can effectively inhibit surgically induced stress and inflammatory response. It also spares opioid use and reduces postoperative pain. This study explored the effects of intraoperative epidural anesthesia on quality of life and central nervous system injury in elderly patients after esophagectomy. Elderly patients who were scheduled for thoracoscopic-laparoscopic esophagectomy were eligible for this randomized controlled study. The patients in the experimental group received general anesthesia combined with epidural anesthesia, while the patients in the control group received only general anesthesia. At the end of surgery, all patients received the same epidural analgesia program before extubation. Health-related quality of life (HRQoL) was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaires (QLQ)-C30 and QLQ-OES18 questionnaires. Two HRQoL questionnaires were filled out before surgery, on day 7 and after the third month postoperatively. The Montreal Cognitive Assessment and serum S100ß level were also evaluated at baseline and on postoperative day 7. Compared with the group without intraoperative epidural anesthesia, the epidural anesthesia group had better quality of life scores particularly in the social, emotional, and global health domains. The symptoms of nausea, constipation, sleep disorders, dysphagia, reflux, pain, and cough difficulty were less severe. In addition, the S100ß content of peripheral blood was also lower on postoperative day 7 (1199.8 pg/mL vs 1341.2 pg/mL, P < 0.001). There was no significant difference in Montreal Cognitive Assessment scores between the 2 groups. Intraoperative epidural anesthesia may improve the quality of life after esophagectomy in elderly patients, and reduce the neuroinflammatory response, compared with the patients receiving general anesthesia only.

Comparison of gastric insufflation using LMA-supreme and I-gel versus tracheal intubation in laparoscopic gynecological surgery by ultrasound: a randomized observational trial.

BACKGROUND: The application of bedside ultrasound to evaluate gastric content and volume can assist in determining aspiration risk. Applying positive pressure ventilation via supraglottic airway devices (SAD) can result in a degree of gastric insufflation. This study assessed and compared the antral cross-sectional area (CSA) in patients undergoing laparoscopic gynecological surgery when managed with different SAD. METHODS: One hundred American Society of Anesthesiologists I or II female patients were assessed for inclusion in this study and divided into three groups of different ventilation devices. Patients were randomly allocated into three groups to receive LMA-Supreme (Group S), I-gel (Group I) or tracheal tube (Group T). The primary outcome was the antral cross-sectional area and secondary outcomes included haemodynamic parameters and postoperative morbidity such as sore throat, hoarseness, dry throat, nausea and vomiting. RESULTS: The antral CSA was not significantly different among three groups before induction (P = 0.451), after induction (P = 0.456) and at the end of surgery (P = 0.195). The haemodynamic variables were significantly higher in the tracheal tube group than in the LMA-Supreme and I-gel groups after insertion (P < 0.0001) and after removal (P < 0.01). Sore throat was detected in none in the I-gel group compare to two patients (6.7%) in the LMA-Supreme group and fifteen patients (50%) in the tracheal tube group. Hoareness was detected in one (3.3%) in the I-gel group compare to two patients (6.7%) in the LMA-Supreme group and eleven patients (36.7%) in the tracheal tube group. CONCLUSIONS: The SADs do not cause obvious gastric insufflation. Thus, LMA-Supreme and I-gel can be widely used as alternative to endotracheal intubation for the short laparoscopic gynecological surgery. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry (ChiCTR1800018212, data of registration, September 2018).

Application of Acupuncture to Attenuate Immune Responses and Oxidative Stress in Postoperative Cognitive Dysfunction: What Do We Know So Far?

Postoperative cognitive dysfunction (POCD) is a common sequela following surgery and hospitalization. The prevention and management of POCD are important during clinical practice. POCD more commonly affects elderly patients who have undergone major surgery and can result in major decline in quality of life for both patients and their families. Acupuncture has been suggested as an effective intervention for many neurological disorders. In recent years, there are increasing interest in the use of acupuncture to prevent and treat POCD. In this review, we summarized the clinical and preclinical evidence of acupuncture on POCD using a narrative approach and discussed the potential mechanisms involved. The experimental details and findings of studies were summarized in tables and analyzed. Most of the clinical studies suggested that acupuncture before surgery could reduce the incidence of POCD and reduce the levels of systematic inflammatory markers. However, their reliability is limited by methodological flaws. Animal studies showed that acupuncture reduced cognitive impairment and the associated pathology after various types of surgery. It is possible that acupuncture modulates inflammation, oxidative stress, synaptic changes, and other cellular events to mitigate POCD. In conclusion, acupuncture is a potential intervention for POCD. More clinical studies with good research design are required to confirm its effectiveness. At the same time, findings from animal studies will help reveal the protective mechanisms, in which systematic inflammation is likely to play a major role.

The timing of propofol administration affects the effectiveness of remote ischemic preconditioning induced cardioprotection in rats.

The cardioprotection of remote ischemic preconditioning (RIPC) is abolished under propofol maintained anesthesia. Transient receptor potential vanilloid 1 (TRPV1) channel is present in the heart, and its activation could induce cardioprotection. Therefore, we tested whether the anesthetic propofol administration phase interfered with the RIPC-induced cardioprotection, and RIPC-induced cardioprotection via the cardiac TRPV1 channel. Male Sprague-Dawley rats were subjected to myocardial 30 minutes of ischemia followed by 2 hours of reperfusion. RIPC consisted of three cycles of 5-minute ischemia/reperfusion applied to a hindlimb. Propofol infusion at 12 mg/kg/h was commenced either at 10 minutes before the start of RIPC in the P-pre + RIPC group, or immediately after myocardial ischemia at the onset of reperfusion (P-post + RIPC) while performing RIPC. These two propofol infusion regimes were applied to another two grou bs without RIPC (P-pre and P-post groups). Infarct size (IS) was assessed by triphenyltetrazolium staining. Heart TRPV1 expression was detected by Western blot and immunofluorescence. RIPC significantly reduced myocardial IS compared with the control group (36.7 ± 3% versus 57.2 ± 4%; P < .01). When propofol was started before RIPC, the IS sparing effect of RIPC was completely abolished. However, propofol infusion starting immediately after myocardial ischemia did not affect RIPC-induced cardioprotection. TRPV1 expression significant increase after RIPC, then propofol inhibited the TRPV1 activation of RIPC if given before RIPC but not after. Our results suggest that the timing of propofol administration is critical to preserve the cardioprotection of RIPC. Propofol might cancel RIPC-induced cardioprotection via the cardiac TRPV1 receptor.

Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer's disease mice.

BACKGROUND: Both human and animal studies have shown beneficial effects of physical exercise on brain health but most tend to be based on aerobic rather than resistance type regimes. Resistance exercise has the advantage of improving both muscular and cardiovascular function, both of which can benefit the frail and the elderly. However, the neuroprotective effects of resistance training in cognitive impairment are not well characterized. METHODS: We evaluated whether short-term resistant training could improve cognitive function and pathological changes in mice with pre-existing cognitive impairment. Nine-month-old 3xTg mouse underwent a resistance training protocol of climbing up a 1-m ladder with a progressively heavier weight loading. RESULTS: Compared with sedentary counterparts, resistance training improved cognitive performance and reduced neuropathological and neuroinflammatory changes in the frontal cortex and hippocampus of mice. In line with these results, inhibition of pro-inflammatory intracellular pathways was also demonstrated. CONCLUSIONS: Short-term resistance training improved cognitive function in 3xTg mice, and conferred beneficial effects on neuroinflammation, amyloid and tau pathology, as well as synaptic plasticity. Resistance training may represent an alternative exercise strategy for delaying disease progression in Alzheimer's disease.