Nutritional Status and Post-Cardiac Surgery Outcomes: An Updated Review with Emphasis on Cognitive Function.

Background/Objectives: Nutritional status significantly influences cardiac surgery outcomes, with malnutrition contributing to poorer results and increased complications. This study addresses the critical gap in understanding by exploring the relationship between pre-operative nutritional status and post-operative cognitive dysfunction (POCD) in adult cardiac patients. Methods: A comprehensive search across key databases investigates the prevalence of malnutrition in pre-operative cardiac surgery patients, its effects, and its association with POCD. Factors exacerbating malnutrition, such as chronic illnesses and reduced functionality, are considered. The study also examines the incidence of POCD, its primary association with CABG procedures, and the impact of malnutrition on complications like inflammation, pulmonary and cardiac failure, and renal injury. Discussions: Findings reveal that 46.4% of pre-operative cardiac surgery patients experience malnutrition, linked to chronic illnesses and reduced functionality. Malnutrition significantly contributes to inflammation and complications, including POCD, with an incidence ranging from 15 to 50%. CABG procedures are particularly associated with POCD, and malnutrition prolongs intensive care stays while increasing vulnerability to surgical stress. Conclusions: The review underscores the crucial role of nutrition in recovery and advocates for a universally recognized nutrition assessment tool tailored to diverse cardiac surgery patients. Emphasizing pre-operative enhanced nutrition as a potential strategy to mitigate inflammation and improve cognitive function, the review highlights the need for integrating nutrition screening into clinical practice to optimize outcomes for high-risk cardiac surgery patients. However, to date, most data came from observational studies; hence, there is a need for future interventional studies to test the hypothesis that pre-operative enhanced nutrition can mitigate inflammation and improve cognitive function in this patient population.

C8-ceramide modulates microglia BDNF expression to alleviate postoperative cognition dysfunction via PKCδ/NF-κB signaling pathway.

Postoperative cognitive dysfunction (POCD) is a kind of serious postoperative complication in surgery with general anesthesia and it may affect patients' normal lives. Activated microglia are thought to be one of the key factors in the regulation of POCD process. Once activated, resident microglia change their phenotype and secrete kinds of cytokines to regulate inflammatory response in tissues. Among these secretory factors, brain-derived neurotrophic factor (BDNF) is considered to be able to inhibit inflammation response and protect nervous system. Therefore, the enhancement of BDNF expression derived from resident microglia is suggested to be potential treatment for POCD. In our study, we focused on the role of C8-ceramide (a kind of interventional drug) and assessed its regulatory effect on improving the expression of BDNF secreted from microglia to treat POCD. According to the results of our study, we observed that C8-ceramide stimulated primary microglia to up-regulate the expression of BDNF mRNA after being treated with lipopolysaccharide (LPS) in vitro. We proved that C8-ceramide had ability to effectively improve POCD of mice after being accepted carotid artery exposure and their abnormal behavior recovered better than that of mice from the surgery group. Furthermore, we also demonstrated that C8-ceramide enhanced the cognitive function of mice via the PKCδ/NF-κB signaling pathway. In general, our study has confirmed a potential molecular mechanism that led to the occurrence of POCD caused by surgery and provided a new clinical strategy to treat POCD.

Long-term cognitive outcomes after surgery and anesthesia: what we find depends on where we look.

Purpose of review: To review how anecdote and narrative medicine, primary cohort studies, epidemiological studies, and the dementia literature can be bridged to understand long-term postoperative cognitive decline. Recent findings: Primary cohort studies have measured recoverable declines in memory and executive function after major surgery, but less-appreciated sources also offer critical insights. Anecdote reveals that functionally-impactful cognitive decline may persist after physical recovery in some patients despite modern medications and monitoring, and that physicians are unprepared to address patients' cognitive concerns. However, epidemiological studies reproducibly demonstrate that elective surgery has no, or a negligible, average impact on cognition in older patients. Cognitively provocative factors - like medical hospital admissions or health factors like diabetes and smoking - are common in late life, and surgery likely contributes minimally to long-term cognitive change for most patients. Summary: Patients should be reassured that, while anecdotes of durable cognitive change after surgery are easily accessible, most patients experience cognitive recovery after major surgery. However, those who do not recover deserve characterization of their symptoms and investigation of modifiable causes to facilitate cognitive recovery.

Dysregulation of the Gut Microbiota Contributes to Sevoflurane-Induced Cognitive Dysfunction in Aged Mice by Activating the NLRP3 Inflammasome.

Postoperative cognitive dysfunction (POCD), a common complication in elderly patients after surgery, seriously affects patients' quality of life. Long-term or repeated inhalation of sevoflurane can cause neuroinflammation, which is a risk factor for POCD. However, the underlying mechanism needs to be further explored. Recent research had revealed a correlation between neurological disorders and changes in the gut microbiota. Dysfunction of the gut microbiota is involved in the occurrence and development of central nervous system diseases. Here, we found that cognitive dysfunction in aged mice induced by sevoflurane exposure (3%, 2 hours daily, for 3 days) was related to gut microbiota dysbiosis, while probiotics improved cognitive function by alleviating dysbiosis. Sevoflurane caused a significant decrease in the abundance of Akkermansia (P<0.05), while probiotics restored the abundance of Akkermansia. Compared to those in the control group, sevoflurane significantly increased the expression of NLRP3 inflammasome-associated proteins in the gut and brain in the sevoflurane-exposed group, thus causing neuroinflammation and synaptic damage, which probiotics can mitigate (con vs. sev, P < 0.01; p+sev vs. sev, P < 0.05). In conclusion, for the first time, our study revealed that dysbiosis of the gut microbiota caused by sevoflurane anesthesia contributes to the NLRP3 inflammasome-mediated neuroinflammation and cognitive dysfunction from the perspective of the gut-brain axis. Perhaps postoperative cognitive impairment in elderly patients can be alleviated or even prevented by regulating the gut microbiota. This study provides new insights and methods for the prevention and treatment of cognitive impairment induced by sevoflurane.

Preoperative recovery sleep ameliorates postoperative cognitive dysfunction aggravated by sleep fragmentation in aged mice by enhancing EEG delta-wave activity and LFP theta oscillation in hippocampal CA1.

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

Comparison of metabolic rates of ropivacaine in cerebrospinal fluid as inferred from plasma concentrations between elderly patients and young patients.

BACKGROUND: With the aging of human society, more and more elderly patients have to undergo surgery and anesthesia. Clinical observations have indicated from time to time that spinal anesthesia in the elderly appears to last longer than in young people, although there is limited research in this area and the mechanism is unclear at present time. This research work is expected to help understand the decline of local anesthetic metabolism in cerebrospinal fluid of elderly patients so as to help them with precise anesthesia and rapid rehabilitation. METHODS: Twenty patients with spinal anesthesia in orthopedic lower limb surgery were selected to study the rate of drug metabolism in cerebrospinal fluid in two age groups, i.e.,18-30 years old and 75-90 years old. Ropivacaine in peripheral blood is used as a probe to reflect the speed of drug metabolism in cerebrospinal fluid. The contents of total Aß protein and hyaluronic acid in the cerebrospinal fluid were investigated as well. RESULTS: The equivalent dose of ropivacaine anesthetizes the elderly group for a longer time. The metabolism rate of ropivacaine in an elderly patient was slower than that of a young patient. No significant difference in total Aß protein between the two groups was observed while hyaluronic acid in the elderly group was significantly higher than that in the young group. CONCLUSIONS: This study shows that the dose of ropivacaine should be reduced when used for anesthesia in elderly patients. The cumulation of ropivacaine and HA appears to imitate the degeneration of central lymphatic circulation metabolism in elderly people.

Liraglutide improves sevoflurane-induced postoperative cognitive dysfunction via activating autophagy and inhibiting apoptosis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. Liraglutide (LRG) has high homology (97%) with natural glucagon like peptide-1, and it has been proved to be effective in some nervous system diseases. Whether LRG could regulate POCD has not been reported. METHODS: Sevoflurane (Sev) was used to simulate postoperative cognitive dysfunction (POCD) model. Morris water maze test was performed to evaluate the memory ability and neurological function of rats. Escape latency, swim distance, crossing platform times, average velocity, and targeting quadrant time were analyzed. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively. RESULTS: LRG significantly improved the memory ability and neurological function of Sev-treated rats, but 3-MA reversed the effects of LRG. LRG remarkably inhibited apoptosis but up-regulated autophagy related proteins both in vivo and in vitro levels. However, knocking down AMPK could markedly reverse the influence of LRG on apoptosis, autophagy, and cell apoptosis. CONCLUSIONS: LRG induced autophagy activation can maintain cell homeostasis and promote cell survival by blocking the apoptotic pathway. LRG could improve Sev-induced POCD via activating autophagy, inhibiting apoptosis, and regulating AMPK/mTOR signaling pathway. This study provides a novel therapeutic strategy for the prevention and treatment of POCD.

SS-31 inhibits mtDNA-cGAS-STING signaling to improve POCD by activating mitophagy in aged mice.

BACKGROUND: Neuroinflammation is crucial in the development of postoperative cognitive dysfunction (POCD), and microglial activation is an active participant in this process. SS-31, a mitochondrion-targeted antioxidant, is widely regarded as a potential drug for neurodegenerative diseases and inflammatory diseases. In this study, we sought to explore whether SS-31 plays a neuroprotective role and the underlying mechanism. METHODS: Internal fixation of tibial fracture was performed in 18-month-old mice to induce surgery-associated neurocognitive dysfunction. LPS was administrated to BV2 cells to induce neuroinflammation. Neurobehavioral deficits, hippocampal injury, protein expression, mitophagy level and cell state were evaluated after treatment with SS-31, PHB2 siRNA and an STING agonist. RESULTS: Our study revealed that SS-31 interacted with PHB2 to activate mitophagy and improve neural damage in surgically aged mice, which was attributed to the reduced cGAS-STING pathway and M1 microglial polarization by decreased release of mitochondrial DNA (mtDNA) but not nuclear DNA (nDNA). In vitro, knockdown of PHB2 and an STING agonist abolished the protective effect of SS-31. CONCLUSIONS: SS-31 conferred neuroprotection against POCD by promoting PHB2-mediated mitophagy activation to inhibit mtDNA release, which in turn suppressed the cGAS-STING pathway and M1 microglial polarization.

Postoperative cognitive dysfunction-current research progress.

Postoperative cognitive dysfunction (POCD) commonly occurs after surgery, particularly in elderly individuals. It is characterized by a notable decline in cognitive performance, encompassing memory, attention, coordination, orientation, verbal fluency, and executive function. This reduction in cognitive abilities contributes to extended hospital stays and heightened mortality. The prevalence of POCD can reach 40% within 1 week following cardiovascular surgery and remains as high as 17% 3 months post-surgery. Furthermore, POCD exacerbates the long-term risk of Alzheimer's disease (AD). As a result, numerous studies have been conducted to investigate the molecular mechanisms underlying POCD and potential preventive strategies. This article provides a review of the research progress on POCD.

Early postoperative neurocognitive complications in elderly patients: comparing those with and without preexisting mild cognitive impairment- a prospective study.

BACKGROUND: As societies age, increasing numbers of older adults undergo surgeries with anesthesia. Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) frequently occur in older surgical patients. Most of these patients already have preoperative mild cognitive impairment (MCI). However, the correlation between MCI and POD remains unclear. This study aimed to determine the incidence of POD in elderly patients with and without preexisting MCI. METHODS: A prospective study enrolled patients aged 60 years and above scheduled for major surgeries between December 2017 and April 2022. Preoperative MCI was determined by a Montreal Cognitive Assessment (MoCA) score between 18 and 24. POD was diagnosed using criteria from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). POCD was characterized by a MoCA score reduction of 2 or more points from the preoperative score. The primary outcome was the incidence of POD within the first 72 h postoperatively. Secondary outcomes encompassed other postoperative complications, including POCD. RESULTS: The study comprised 223 elderly patients with MCI and 56 without MCI. The incidence of POD was 16.6% in the MCI group and 14.3% in the non-MCI group (P = 0.839). POCD occurred in 24.3% of MCI patients and 50% of non-MCI patients (P = 0.001). There were no significant differences in other postoperative complications between the groups. Postoperatively, the MCI group notably declined in visuospatial, attention, and orientation domains, while the non-MCI group declined in all domains except delayed recall. CONCLUSIONS: The incidence of POD was similar in the MCI and non-MCI groups. However, the non-MCI group demonstrated a higher incidence of POCD than the MCI group. This was identified by a reduction in postoperative MoCA scores for the visuospatial, naming, attention, language, abstraction, and orientation domains. These findings underscore the importance of postoperative cognitive assessments for both elderly patients with preexisting MCI and those with previously intact cognitive functions. TRIAL REGISTRATION: This trial was retrospectively registered in the Thai Clinical Trials Registry on 15/01/2019 (registration number: TCTR20190115001).

Peripheral cholinesterase activity is not correlated with postoperative delirium in urological surgery.

The value of biomarkers, such as acetylcholinesterase and butyrylcholinesterase, for guiding perioperative patients suffering from postoperative delirium and/or (possibly related) postoperative cognitive dysfunction is unclear. Only recently have different biomarkers are being explored to assess postoperative delirium's occurrence and/or course. The aim of this work is to investigate whether acetylcholinesterase and butyrylcholinesterase can help detect increased risks of the development and course of postoperative delirium in urological patients undergoing surgery. In total, 45 urology patients were screened. During five perioperative time points (meaning preoperative and postoperative), acetylcholinesterase or butyrylcholinesterase concentrations from serum were correlated with three perioperative postoperative delirium and two perioperative postoperative cognitive dysfunction investigations. Results showed neither a significant decline of either acetylcholinesterase or butyrylcholinesterase concentration before and after surgery, nor a significant correlation with postoperative delirium. Furthermore, significant postoperative cognitive dysfunction could not be detected in this perioperative urological collective.

Rutin prevents pyroptosis and M1 microglia via Nrf2/Mac-1/caspase-1-mediated inflammasome axis to improve POCD.

BACKGROUND: Neuroinflammation following peripheral surgery plays a key role in postoperative cognitive dysfunction (POCD) development and there is no effective therapy to inflammation-mediated cognitive impairment. Recent studies showed that rutin, a natural flavonoid compound, conferred neuroprotection. However, the effects and mechanisms of rutin on cognition of surgical and aged mice and LPS-induced BV2 need deeper exploration. METHODS: The effect of rutin in vivo and vitro were evaluated by Morris water maze test, HE stainin, Golgi-Cox staining, IF, IHC, RT-PCR, Flow Cytometer and Western blotting. In vivo, aged mice were treated with rutin and surgery. In vitro, rutin, Nrf2 knockdown, MAC-1 overexpression and VX765, a caspase-1 inhibitor, were administration on BV2 microglial cells. RESULTS: Surgery led to compensatory increase in nuclear Nrf2 and rutin could further increase it. Neural damage was accompanied with high level in MAC-1, caspase-1-mediated pyroptosis and M1 microglia, while rutin recovered the process. Nrf2 inhibition abolished the effect of rutin with the increase of MAC-1, caspase-1-mediated pyroptosis and M1 microglia. Activation of MAC-1 abrogated protection of rutin by increase in pyroptosis and M1 microglia. Finally, we found that treatment with VX765 improved injury and increased M2 microglia against overexpression of MAC-1. CONCLUSIONS: Our study indicated that rutin may be a potential therapy in POCD and exerted neural protection via Nrf2/ Mac-1/ caspase-1-mediated inflammasome axis to regulate pyroptosis and microglial polarization.

Akkermansia muciniphila-derived small extracellular vesicles attenuate intestinal ischemia-reperfusion-induced postoperative cognitive dysfunction by suppressing microglia activation via the TLR2/4 signaling.

Akkermansia muciniphila (AKK) bacteria improve the functions of theere intestinal and blood-brain barriers (BBB) via their extracellular vesicles (AmEvs). However, their role in postoperative cognitive dysfunction (POCD) and its underlying mechanisms remain unclear. To investigate, we used C57BL/6 J mice divided into five groups: Sham, POCD, POCD+Akk, POCD+Evs, and POCD+Evs + PLX5622. POCD was induced through intestinal ischemia-reperfusion (I/R). The mice's cognitive function was assessed using behavioral tests, and possible mechanisms were explored by examining gut and BBB permeability, inflammation, and microglial function. Toll-like receptor (TLR) 2/4 pathway-related proteins were also investigated both in vitro and in vivo. PLX5622 chow was employed to eliminate microglial cells. Our findings revealed a negative correlation between AKK abundance and POCD symptoms. Supplementation with either AKK or AmEvs improved cognitive function, improved the performance of the intestinal barrier and BBB, and decreased inflammation and microglial activation in POCD mice compared to controls. Moreover, AmEvs treatment inhibited TLR2/4 signaling in the brains of POCD mice and LPS-treated microglial cells. In microglial-ablated POCD mice, however, AmEvs failed to protect BBB integrity. Overall, AmEvs is a potential therapeutic strategy for managing POCD by enhancing gut and BBB integrity and inhibiting microglial-mediated TLR2/4 signaling.

MMP-9 inhibition alleviates postoperative cognitive dysfunction by improving glymphatic function via regulating AQP4 polarity.

Postoperative cognitive dysfunction (POCD) is a common complication after surgery, characterized by deficits in memory, attention and cognitive flexibility. However, the underlying mechanisms of POCD remain unclear. Neuroinflammation and blood-brain barrier disruption have been implicated as potential pathological processes. This study explores the neuroprotective effects and mechanisms of the matrix metalloproteinase（MMP-9）inhibitor GM6001 against POCD. We hypothesize GM6001 may reduce neuroinflammation and preserve blood-brain barrier integrity through direct inhibition of MMP-9. Moreover, GM6001 may stabilize aquaporin-4 polarity and glymphatic clearance function by modulating MMP-9-mediated cleavage of dystroglycan, a key protein for aquaporin-4 anchoring. Our results demonstrate GM6001 alleviates postoperative cognitive deficits and neuroinflammation. GM6001 also preserves blood-brain barrier integrity and rescues aquaporin-4 mislocalization after surgery. This study reveals a novel dual role for MMP-9 inhibition in cognitive protection through direct anti-neuroinflammatory effects and regulating aquaporin-4 membrane distribution. Targeting MMP-9 may represent a promising strategy to prevent postoperative cognitive dysfunction by integrating multiple protective mechanisms.

J147 affects cognition and anxiety after surgery in Zucker rats.

Vulnerable patients are at risk for neuroinflammation-mediated post-operative complications, including depression (POD) and cognitive dysfunction (POCD). Zucker rats, expressing multiple risk factors for post-operative complications in humans, may provide a clinically relevant model to study pathophysiology and explore potential interventions. J147, a newly developed anti-dementia drug, was shown to prevent POCD in young healthy rats, and improved early post-surgical recovery in Zucker rats. Aim of the present study was to investigate POCD and the therapeutic potential of J147 in male Zucker rats. Risk factors in the Zucker rat strain were evaluated by comparison with lean littermates. Zucker rats were subjected to major abdominal surgery. Acute J147 treatment was provided by a single iv injection (10 mg/kg) at the start of surgery, while chronic J147 treatment was provided in the food (aimed at 30 mg/kg/day), starting one week before surgery and up to end of protocol. Effects on behavior were assessed, and plasma, urine and brain tissue were collected and processed for immunohistochemistry and molecular analyses. Indeed, Zucker rats displayed increased risk factors for POCD, including obesity, high plasma triglycerides, low grade systemic inflammation, impaired spatial learning and decreased neurogenesis. Surgery in Zucker rats reduced exploration and increased anxiety in the Open Field test, impaired short-term spatial memory, induced a shift in circadian rhythm and increased plasma neutrophil gelatinase-associated lipocalin (NGAL), microglia activity in the CA1 and blood brain barrier leakage. Chronic, but not acute J147 treatment reduced anxiety in the Open Field test and protected against the spatial memory decline. Moreover, chronic J147 increased glucose sensitivity. Acute J147 treatment improved long-term spatial memory and reversed the circadian rhythm shift. No anti-inflammatory effects were seen for J147. Although Zucker rats displayed risk factors, surgery did not induce extensive POCD. However, increased anxiety may indicate POD. Treatment with J147 showed positive effects on behavioral and metabolic parameters, but did not affect (neuro)inflammation. The mixed effect of acute and chronic treatment may suggest a combination for optimal treatment.

Association between anaesthesia-related factors and postoperative neurocognitive disorder: a post-hoc analysis.

BACKGROUND: Postoperative neurocognitive disorder (pNCD) is common after surgery. Exposure to anaesthetic drugs has been implicated as a potential cause of pNCD. Although several studies have investigated risk factors for the development of cognitive impairment in the early postoperative phase, risk factors for pNCD at 3 months have been less well studied. The aim of this study was to identify potential anaesthesia-related risk factors for pNCD at 3 months after surgery. METHODS: We analysed data obtained for a prospective observational study in patients aged ≥ 65 years who underwent surgery for excision of a solid tumour. Cognitive function was assessed preoperatively and at 3 months postoperatively using 5 neuropsychological tests. Postoperative NCD was defined as a postoperative decline of ≥ 25% relative to baseline in ≥ 2 tests. The association between anaesthesia-related factors (type of anaesthesia, duration of anaesthesia, agents used for induction and maintenance of anaesthesia and analgesia, the use of additional vasoactive medication, depth of anaesthesia [bispectral index] and mean arterial pressure) and pNCD was analysed using logistic regression analyses. Furthermore, the relation between anaesthesia-related factors and change in cognitive test scores expressed as a continuous variable was analysed using a z-score. RESULTS: Of the 196 included patients, 23 (12%) fulfilled the criteria for pNCD at 3 months postoperatively. A low preoperative score on Mini-Mental State Examination (OR, 8.9 [95% CI, (2.8-27.9)], p < 0.001) and a longer duration of anaesthesia (OR, 1.003 [95% CI, (1.001-1.005)], p = 0.013) were identified as risk factors for pNCD. On average, patients scored higher on postoperative tests (mean z-score 2.35[± 3.13]). CONCLUSION: In this cohort, duration of anaesthesia, which is probably an expression of the complexity of the surgery, was the only anaesthesia-related predictor of pNCD. On average, patients' scores on cognitive tests improved postoperatively.

Activation of the CD200/CD200R1 axis attenuates neuroinflammation and improves postoperative cognitive dysfunction via the PI3K/Akt/NF-κB signaling pathway in aged mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a neurological complication occurring after anesthesia and surgery. Neuroinflammation plays a critical role in the pathogenesis of POCD, and the activation of the cluster of differentiation 200 (CD200)/CD200R1 axis improves neurological recovery in various neurological disorders by modulating inflammation. The aim of this study was to investigate the impact and underlying mechanism of CD200/CD200R1 axis on POCD in aged mice. METHODS: The model of POCD was established in aged mice. To assess the learning and memory abilities of model mice, the Morris water maze test was implemented. CD200Fc (CD200 fusion protein), CD200R1 Ab (anti-CD200R1 antibody), and 740Y-P (a specific PI3K activator) were used to evaluate the effects of the CD200/CD200R1/PI3K/Akt/NF-κB signaling pathway on hippocampal microglial polarization, neuroinflammation, synaptic activity, and cognition in mice. RESULTS: It was observed that anesthesia/surgery induced cognitive decline in aged mice, increased the levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1 ß and decreased the levels of postsynaptic density protein 95 (PSD-95), synaptophysin (SYN) in the hippocampus. Moreover, CD200Fc and 740Y-P attenuated neuroinflammation and synaptic deficits and reversed cognitive impairment via the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt)/nuclear factor-kappa B (NF-κB) signaling pathway, whereas CD200R1 Ab administration exerted the opposite effects. Our results further show that the CD200/CD200R1 axis modulates M1/M2 polarization in hippocampal microglia via the PI3K/Akt/NF-κB signaling pathway. CONCLUSIONS: Our findings indicate that the activation of the CD200/CD200R1 axis reduces neuroinflammation, synaptic deficits, and cognitive impairment in the hippocampus of aged mice by regulating microglial M1/M2 polarization via the PI3K/Akt/NF-κB signaling pathway.

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.

Cognitive outcomes in patients treated with neuromuscular electrical stimulation after coronary artery bypass grafting.

Objective: Mechanisms of neurocognitive injury as post-operative sequelae of coronary artery bypass grafting (CABG) are not understood. The systemic inflammatory response to surgical stress causes skeletal muscle impairment, and this is also worsened by immobility. Since evidence supports a link between muscle vitality and neuroprotection, there is a need to understand the mechanisms by which promotion of muscle activity counteracts the deleterious effects of surgery on long-term cognition. Methods: We performed a clinical trial to test the hypothesis that adding neuromuscular electrical stimulation (NMES) to standard rehabilitation care in post-CABG patients promotes the maintenance of skeletal muscle strength and the expression of circulating neuroprotective myokines. Results: We did not find higher serum levels of neuroprotective myokines, except for interleukin-6, nor better long-term cognitive performance in our intervention group. However, a greater increase in functional connectivity at brain magnetic resonance was seen between seed regions within the default mode, frontoparietal, salience, and sensorimotor networks in the NMES group. Regardless of the treatment protocol, patients with a Klotho increase 3 months after hospital discharge compared to baseline Klotho values showed better scores in delayed memory tests. Significance: We confirm the potential neuroprotective effect of Klotho in a clinical setting and for the first time post-CABG.

Recent advances in nanobiosensors for sustainable healthcare applications: A systematic literature review.

The need for novel healthcare treatments and drugs has increased due to the expanding human population, detection of newer diseases, and looming pandemics. The development of nanotechnology offers a platform for cutting-edge in vivo non-invasive monitoring and point-of-care-testing (POCT) for rehabilitative disease detection and management. The advancement and uses of nanobiosensors are currently becoming more common in a variety of scientific fields, such as environmental monitoring, food safety, biomedical, clinical, and sustainable healthcare sciences, since the advent of nanotechnology. The identification and detection of biological patterns connected to any type of disease (communicable or not) have been made possible in recent years by several sensing techniques utilizing nanotechnology concerning biosensors and nanobiosensors. In this work, 2218 articles are drawn and screened from six digital databases out of which 17 were shortlisted for this review by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) technique. As a result, this study uses a systematic methodology to review some recently developed extremely sensitive nanobiosensors, along with their biomedical, point-of-care diagnostics (POCD), or healthcare applications and their capabilities, particularly for the prediction of some fatal diseases based on a few of the most recent publications. The potential of nanobiosensors for medicinal, therapeutic, or other sustainable healthcare applications, notably for ailments diagnostics, is also recognized as a way forward in the manifestation of future trends.