Microglia-mediated neuroinflammation is increasingly recognized as a contributor to neurodegenerative disease progression. However, how microglia contribute to neuroinflammation-induced cognitive dysfunction remains unclear. Galectin-3 (Gal-3) is a microglia-enriched lectin that regulates inflammatory signaling and phagocytosis, a plausible mediator linking neuroinflammation to cognitive dysfunction. In a lipopolysaccharide (LPS)-induced mouse model of neuroinflammation (0.5 mg/kg for 7 consecutive days), cognitive function was evaluated using the open field, Y-maze, and novel object recognition tests. In vivo CA1 extracellular electrophysiological recordings were used to analyze local field potentials (LFPs) and single-unit spiking activity. Dendritic morphology was evaluated by Golgi staining, and synaptic markers were quantified by immunofluorescence. In hippocampal CA1, microglia exhibited increased Gal-3 expression, enhanced phagocytic activity, and selectively increased engulfment of excitatory synapses. Systemic pharmacologic inhibition with TD139 and microglia-targeted Lgals3 knockdown (AAV-shLgals3 in Cx3cr1-CreERT2 mice) preserved excitatory synapses, restored CA1 gamma power, and improved cognitive performance in the neuroinflammation model. These results identify Gal-3-dependent microglial phagocytosis as a key mechanism linking neuroinflammation to cognitive dysfunction.

Background:Perioperative pain poses a significant challenge for surgical patients, with regional anesthesia commonly employed for postoperative pain relief. However, the utility of regional anesthesia is limited by the lack of real-time visualization during drug delivery and the rapid diffusion of anesthetics, which result in imprecise targeting and short duration of analgesia. Methods:An innovative ultrasound-guided drug sustained-release capsules were fabricated by bioinspired adhesive polylactic-co-glycolic acid (PLGA) loaded with ropivacaine microbubbles (APRMs). Ropivacaine release and ultrasonographic experiments of APRMs were conducted in vitro. For in vivo evaluation, a total of 127 adult male Sprague-Dawley rats (200-250 g) were used. Then, incision surgery and SNI-induced neuropathic pain were conducted for adult male rats to verify the ropivacaine release of APRMs in vivo. Ultrasound imaging was performed to confirm the ultrasonic visualization of APRMs. The in vivo fluorescence imaging experiment was conducted for the adhesion property of APRMs. Finally, systemic toxicity and tissue reaction were histologically evaluated. Results:APRMs achieved real-time visualization during drug delivery and significantly prolonged antinociceptive effects, maintaining mechanical analgesia for 9 days and thermal analgesia for up to 15 days, whereas free ropivacaine produced only transient effects (mechanical: approximately 24 h; thermal: approximately 4 h). Histological assessments revealed no toxicity or adverse tissue reactions, underscoring the safety of APRMs. Conclusion:APRMs represent a novel and promising strategy for pain management by integrating sustained anesthetic release, bioinspired adhesive properties for prolonged retention, and contrast-enhanced ultrasonography (CEUS) for real-time visualization. While these findings are encouraging, further in vivo validation and extended preclinical studies will be essential to confirm safety and efficacy before considering translation into clinical practice.

Background:Postoperative delirium (POD) is a prevalent and devastating complication in elderly patients undergoing major surgery, marked by substantial increases in morbidity, mortality, and long-term cognitive decline. However, treatment and prevention methods are limited. Accumulating evidence suggests that vagus nerve stimulation effectively enhances cognitive function. Objective:To evaluate the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) on POD in elderly patients undergoing major non-cardiac surgery. Methods:Patients aged ≥65 years scheduled for major non-cardiac surgery were randomly assigned to either the active taVNS group or the sham taVNS group, with stimulation targeting the cymba conchae or earlobe, respectively. In both groups, stimulation was initiated 5 minutes prior to anesthesia induction and continued until the end of surgery. The only difference between the two groups was the stimulation site. The primary outcome was the incidence of POD during the first 3 postoperative days. Results:A total of 150 patients (median age, 73 years; 96 women [64%]) completed this trial. The incident POD risk was 12% (n = 9) vs 25.3% (n = 19) in active-taVNS and sham-taVNS groups, respectively (relative risk, 0.47; 95% CI, 0.23-0.98; P = 0.036). The mediation analysis revealed that postoperative sleep quality played a significant mediating role in the effect of taVNS on POD (z = -2.30, P = 0.02). Conclusion:In this study, taVNS reduces the incidence of POD in elderly patients undergoing major non-cardiac surgery, possibly by improving postoperative sleep quality. We suggest that this non-invasive neuromodulation technique could be considered as a potential preventive strategy for POD. Further validation in future large-scale randomized controlled trials is warranted.

Background:Multimorbidity is associated with adverse outcomes among older adult surgical patients, yet its role in postoperative delirium (POD) remains unclear. In the present study, we hypothesized that distinct pattern of multimorbidity is associated with increased incidence of POD. Methods:From January 2024 to December 2024, 819 older adult patients were recruited at the Second Affiliated Hospital of Nanjing Medical University. Latent class analysis was used to identify patient subgroups based on disease composition. Mediation effect analysis explored the relationship between subgroups, Edmonton frail scale (EFS), and cognitive performance. Multinomial logistic regression model was employed to predict the subgroup to which patients with different diseases belong. Results:Three clinically distinct multimorbidity subgroups were identified. Significant differences in EFS, mini-mental state examination (MMSE), and POD were observed among subgroups (p < 0.05). After adjustment for age and MMSE, we found that subgroup 2 mediated the occurrence of POD through frailty [Indirect effect = 0.043; (95%CI = 0.019 ~ 0.070)]. Multinomial logistic regression model demonstrated good predictive power for subgroups, with AUROC scores as follows: subgroup 1 = 0.993, subgroup 2 = 0.977, and subgroup 3 = 0.990. The AUPRC scores were also strong, with subgroup 1 = 0.995, subgroup 2 = 0.886, and subgroup 3 = 0.974. Conclusion:We identified a specific pattern of multimorbidities significantly associated with frailty, cognitive impairment, and POD risk. The high-risk subgroup's effect on POD was partially mediated by frailty. Multinomial logistic regression model accurately predicted subgroup membership, offering a potential tool for preoperative risk stratification.

Microglial pyroptosis-mediated neuroinflammation emerges as a critical pathogenic mechanism underlying sepsis-associated encephalopathy (SAE). Epigenetic modifications, especially histone acetylation states, exert fundamental regulatory effects on microglial pyroptosis. Among these, histone deacetylase 3 (HDAC3) has been identified as a central epigenetic regulator orchestrating these processes. This study investigates the functional role of HDAC3 in microglial pyroptosis and its underlying mechanisms contributing to SAE-related cognitive impairment. To explore this, male C57BL/6 mice subjected to cecal ligation and puncture (CLP) served as the SAE model. We employed RGFP966, a selective HDAC3 inhibitor, administered at 20 mg/kg/day via daily subcutaneous injections for 14 days starting 2 h prior to CLP surgery. To specifically examine HDAC3’s role in microglia, we bilaterally injected recombinant adeno-associated virus (rAAV)-expressing rEGFP under the control of a DIO promoter into the hippocampus of Cx3cr1-Cre mice to achieve selective overexpression. Our data demonstrate that HDAC3 in microglia activates pyroptosis through the STING/NLRP3 pathway, exacerbating oxidative stress responses and impairing neural activity, ultimately leading to cognitive deficits in SAE. Furthermore, HDAC3 overexpression in microglia recapitulates these pathological changes, underscoring its central role in driving disease progression. Conversely, RGFP966 treatment effectively attenuates these abnormalities by suppressing HDAC3 expression and downstream inflammatory pathways. These findings highlight the therapeutic potential of targeting microglial HDAC3 to mitigate neuroinflammation and cognitive dysfunction in SAE, offering a novel direction for future clinical applications.

Chronic sleep deprivation (CSD) can induce cognitive impairment, but its molecular mechanism remains unclear. In this study, initial m⁶A RNA sequencing of the hippocampal CA3 region in CSD rats, coupled with differential gene expression analysis of the total RNA fraction, revealed downregulation of METTL3, which was consistent with impaired performance in the Morris Water Maze (MWM) and confirmed by qRT-PCR and Western blot. Further investigation showed that, in HT-22 cells, METTL3 knockdown exacerbated rapamycin-induced apoptosis. RNA sequencing of METTL3-knockdown cells identified gene modules and specific differentially expressed genes associated with METTL3 loss. Differential expression analysis revealed that CDKN1A was significantly upregulated following METTL3 knockdown. Methylated RNA immunoprecipitation followed by qPCR (MeRIP-qPCR) further showed that METTL3 knockdown reduced the m⁶A methylation level of CDKN1A mRNA. In vivo, METTL3 overexpression in CSD rats reduced CDKN1A levels, decreased neuronal apoptosis, improved spatial memory, and alleviated CA3 neuronal damage. In vitro, METTL3 knockdown upregulated CDKN1A and promoted apoptosis in HT-22 cells, while CDKN1A knockdown reversed this effect. Collectively, our results demonstrate that METTL3 downregulation promotes CSD-induced cognitive impairment by driving CDKN1A-dependent neuronal apoptosis, thereby identifying the METTL3/CDKN1A axis as a potential therapeutic target.

The relationship between peripheral and central biomarkers in mild cognitive impairment (MCI), and the potential role of blood-brain barrier (BBB) dysfunction in this process, remain unclear. MCI, an intermediate state between normal aging and dementia, is characterized by early neuroinflammation and neuronal injury, yet how systemic markers reflect central pathology is poorly understood. In this study, we enrolled 74 participants, including 37 MCI patients and 37 cognitively normal controls. Based on the CSF/serum albumin ratio, subjects were classified into four groups-NC (cognitively normal with intact BBB), NMCI (MCI with intact BBB), BC (cognitively normal with BBB disruption), and BMCI (MCI with BBB disruption)-and further grouped as BBB-intact or BBB-disrupted. Serum and cerebrospinal fluid (CSF) levels of interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP), and neurofilament light (Nf-L) were measured using enzyme-linked immunosorbent assay. Spearman correlation analysis was applied to examine peripheral-central associations. No significant correlations were observed in NC or NMCI groups. A moderate serum-CSF GFAP correlation was found in the BC group (r = 0.446, P = 0.033), which became markedly stronger in the BMCI group (r = 0.753, P < 0.001). In the BBB-disrupted group, significant correlations were detected for GFAP (r = 0.652, P < 0.001), IL-4 (r = 0.412, P = 0.003), IL-6 (r = 0.296, P = 0.035), and TNF-α (r = 0.352, P = 0.011), with GFAP showing the strongest association. In contrast, within the BBB-intact group, only serum-CSF IL-6 correlation reached significance (r = 0.469, P = 0.024). These findings suggest that BBB disruption markedly enhances peripheral-central biomarker associations, especially for GFAP, highlighting the regulatory role of BBB integrity in linking systemic inflammation, neuronal injury, and MCI pathophysiology.

Critical dynamics are thought to support optimal information processing in the brain. Although disrupted criticality has been implicated in various neuropsychiatric and neurodegenerative disorders, whether neuroinflammation impairs cognition by disrupting brain criticality remains unclear. Here, we investigated how neuroinflammation alters hippocampal CA1 network criticality and whether this disruption contributes to cognitive impairments. Using a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation, we combined in vivo electrophysiology, behavioral assays, morphological analysis, and molecular interventions to investigate the effects of neuroinflammation on hippocampal network dynamics and cognitive function. We found that LPS-induced neuroinflammation reduced the excitability of excitatory neurons and weakened functional connectivity, accompanied by enhanced microglial pruning of excitatory synapses, dendritic spine loss, and AMPA receptor endocytosis. These structural and cellular alterations were associated with a shift of CA1 network dynamics toward a subcritical state, as indicated by an increased deviation from the criticality coefficient, and this network disruption was accompanied by impairments in working and recognition memory. To determine whether these alterations contribute to disrupted criticality and cognitive impairments, we selectively manipulated neuronal excitability and inter-neuronal interactions. Chemogenetic activation of CaMKII-positive neurons restored neuronal excitability, rescued network criticality, and improved cognitive performance. Likewise, inhibition of AMPA receptor endocytosis with the TAT-GluA23Y peptide restored inter-neuronal connectivity, and rescued both network criticality and cognitive function. Together, these findings support that neuroinflammation-driven synaptic alterations impair cognition, at least in part, by disrupting hippocampal criticality.

Sepsis-associated encephalopathy (SAE), a devastating neurological complication of systemic inflammation, affects approximately 70

Background:Liposomal bupivacaine provides prolonged analgesia, but evidence for its efficacy in anterior quadratus lumborum block (QLB) for laparoscopic gynecological surgery remains limited. This study compared liposomal bupivacaine combined with bupivacaine (LB) versus bupivacaine combined with dexamethasone (BD). Methods:In this randomized controlled trial, 136 patients undergoing laparoscopic hysterectomy or myomectomy were randomized to receive anterior QLB with either LB or BD. The primary outcome was cumulative oxycodone consumption within 48 h postoperatively. Secondary outcomes included oxycodone use across predefined postoperative intervals, resting and cough numerical rating scale (NRS) pain scores, pain area under the curve (AUC), opioid-free proportion within 72 h, duration of analgesia, and postoperative adverse events. Results:67 LB and 69 BD patients completed the study. Cumulative 48-h oxycodone consumption was comparable between the two groups (1 mg [0-3] vs. 2 mg [0-6], P = 0.192; median difference 0 mg, 95% CI -2 to 0 mg). Oxycodone use across 0-12, 0-24, 0-48, 48-72, and 0-72 h did not differ significantly. Although the LB group showed statistically lower oxycodone use during the 12-24 and 24-48 h periods, median values were 0 mg in both groups. Resting and cough NRS scores and 72-h pain AUC were similar between the two groups. Approximately 45% of patients remained opioid-free during the first 72 h after surgery in both groups. The duration of analgesia was significantly longer in the BD group (1,553 vs. 561 minutes, P < 0.001). Adverse event rates were low and comparable. Conclusion:Liposomal bupivacaine combined with bupivacaine did not reduce opioid consumption or improve analgesic outcomes compared with bupivacaine-dexamethasone for anterior QLB in laparoscopic gynecological surgery. Both regimens provided effective and well-tolerated analgesia. Trial Registration:Chinese Clinical Trials Registry Platform (chictr.org.cn): ChiCTR2500096893.

Objective To investigate the correlation between perioperative dynamic change of C-reactive protein(ΔCRP)and postoperative delirium(POD),and to evaluate its predictive value for POD.Methods A total of 574 elderly patients undergoing elective general anesthesia at the Second Affiliated Hospital of Nanjing Medical University from February 2021 to July 2025 were enrolled and divided into a POD group(n=118)and a non-POD(N-POD)group(n=456)based on the occurrence of POD.Baseline data and laboratory test results were collected,and the CRP levels one day before surgery and the highest CRP value within three days after surgery were recorded to calculate ΔCRP.The correlation of ΔCRP level with POD was analyzed and the predictive value of ΔCRP level for POD was assessed.Results POD occurred in 118 patients.Compared with N-POD group,the proportion of urban residents,educational level,preoperative mini-mental state examination(MMSE)scores,the levels of red blood cells,hemoglobin,albumin,alanine aminotransferase,and creatine kinase were significantly lower,while American Society of Anesthesiologists(ASA)classification,intraoperative blood loss,total intraoperative fluid input,operation time,and the levels of prothrombin time,fibrinogen,D-dimer,preoperative CRP,postoperative CRP,and ΔCRP were significantly higher in POD group(P＜0.05).Multivariable logistic regression analysis showed significant association between ΔCRP and POD(increased by 1 mg/L:OR=1.013,95％CI:1.008-1.018;increased by 10 mg/L:OR=1.136,95％CI:1.079-1.196).The patients were divided into 4 groups according to quartile of ΔCRP,and the risk of POD in Q4 group was significantly increased(OR=5.078,95％CI:2.332-11.059).The AUC of ΔCRP for predicting POD was 0.788(95％CI:0.746-0.830).Conclusions Perioperative ΔCRP exhibits a significant dose-dependent positive correlation with the risk of POD and is an independent risk factor for POD occurrence.

BACKGROUND:Surgical procedures are essential interventions for treating disease and saving lives. However, their relationship with biological age remains unclear. METHODS:This cross-sectional analysis included up to 472,279 UK Biobank participants. Surgical exposure was defined as surgical procedures occurring within 1, 3, and 5 years before baseline. Biological aging was assessed using PhenoAge acceleration, defined as the residual from regressing PhenoAge derived from multiple clinical biomarkers on chronological age, and leukocyte telomere length (LTL), measured using a validated qPCR method. Multivariable linear regression models were used to assess the associations between the number of surgeries and biological aging markers. Subgroup analyses assessed effect modification by age, frailty, comorbidity burden, and depression. RESULTS:After full adjustment, each additional surgery within 1, 3, and 5 years was associated, on average, with 0.46 (95% CI, 0.43-0.49), 0.26 (95% CI, 0.24-0.27), and 0.20 (95% CI, 0.19-0.21) years higher PhenoAge acceleration, respectively (all P < 0.001). For LTL, the corresponding fully adjusted β (95%CI) were - 0.002(-0.009 to 0.006), -0.003(-0.007 to 0.001), and - 0.002(-0.005 to 0.001) SD, respectively. Surgical exposure was more strongly associated with PhenoAge acceleration among individuals undergoing moderate to high stress surgeries (P for heterogeneity <0.001) and among those with frailty or greater comorbidity burden (P for interaction <0.001). CONCLUSION:Cumulative surgical exposure was associated with modest but detectable differences in PhenoAge acceleration, with associations varying according to surgical burden, surgical timing, and baseline physiological reserve.

Background Postoperative pulmonary complications (PPCs) significantly impair patient recovery, yet reliable predictors remain scarce. T cell and mitochondrial phenotypic marker abnormalities are recognized as key mechanisms underlying immune dysregulation. Accordingly, we hypothesized that quantifying these T cell characteristics could serve as a novel predictive strategy for PPCs. Methods Patients who underwent elective thoracic surgery under general anesthesia were enrolled in this study. Preoperative venous blood samples were collected to measure T cell subsets and their mitochondrial function indicators. Results The occurrence of PPCs was evaluated postoperatively. Among the 176 enrolled patients, 44 (25.0%) developed PPCs. Compared with the non-PPCs group, patients in the PPCs group were older, had longer operative time, and exhibited significantly higher preoperative levels of C-reactive protein, neutrophils, white blood cells, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, D-dimer, and international normalized ratio, while the preoperative lymphocyte percentage was significantly lower (P < 0.05). Regarding T cell related parameters, the PPCs group showed a significantly lower absolute count of CD3+CD4+ T cells, significantly higher percentage and absolute count of CD3+CD4+PD-1+ T cells, and a significantly lower percentage of CD3+CD8+MMP T cells (P < 0.05). Multivariable logistic regression analysis identified the percentage of CD3+CD4+PD-1+ T cells, absolute count of CD3+CD4+PD-1+ T cells, and operative time as independent risk factors for PPCs, while lymphocyte percentage emerged as an independent protective factor. After adjustment using different models, the multivariable model (Model 3) demonstrated that both the percentage and absolute count of CD3+CD4+PD-1+ T cells had good predictive performance for PPCs (P < 0.001). Conclusions Thus, preoperative measurement of T cell subsets indicators may aid in early identification and risk stratification of PPCs after thoracic surgery.

Sepsis-associated encephalopathy (SAE) is a frequent and devastating central nervous system complication of sepsis and portends a poor prognosis. Accumulating data implicate C-type lectin domain family 7 member A (Clec7a) in neuroinflammation and cognitive impairment, however, its specific role in SAE-linked cognitive impairment remains to be defined. Adult male mice received a single intraperitoneal injection of lipopolysaccharide (LPS, 5 mg·kg⁻¹ i.p.) to induce SAE. Four hours later, animals were treated with the Clec7a antagonist laminarin (250 mg·kg⁻¹ i.p.) once daily for three days. Cognitive performance was assessed on days 6–9 post-LPS using the open field, novel object recognition, and Y-maze tests. Hippocampal Clec7a expression was evaluated by Western blotting; microglial number and morphology, myelin integrity, and neuronal activity were assessed by immunofluorescence, Whole-Cell Recordings and transmission electron microscopy. SAE was characterized by marked upregulation of Clec7a and robust microglial activation in the CA1 region of the hippocampus. The LPS challenge increased Clec7a and CD68 expression, triggered excessive microglial phagocytosis of myelin, provoked axonal degeneration and nodal elongation, and reduced neuronal activity - as electrophysiologically demonstrated by hyperpolarized resting membrane potential(RMP), a trend toward an elevated rheobase current, and a decrease in the number of action potentials - along with decreased c-Fos⁺ cell numbers, ultimately leading to cognitive impairment. Laminarin treatment substantially attenuated microglial activation, preserved myelin architecture, restored neuronal activity (evidenced by normalized electrophysiological parameters), increased c-Fos⁺ cell numbers, and rescued cognitive impairment. Clec7a drives microglial activation, leading to aberrant myelin phagocytosis, neuronal hypoactivity, and cognitive impairment in SAE. Pharmacological inhibition of Clec7a reverses these alterations, highlighting Clec7a as a potential therapeutic target for SAE.

Post-intensive care syndrome (PICS) encompasses new or worsening impairments in physical, cognitive, or mental health that manifest and persist after critical illness, yet the burden of PICS in this population remains under-characterized. We sought to quantify the incidence of PICS in sepsis survivors and to identify its independent predictors. We conducted a prospective observational study of adult sepsis patients discharged from the medical ICU of Jinling Hospital, Nanjing University School of Medicine, between October 2024 and February 2025. Comprehensive baseline data—including demographics, clinical characteristics, and ICU interventions—were collected. Standardized telephone and in-person assessments were performed at 1, 3, and 6 months post-discharge to diagnose PICS across physical, cognitive, and mental health domains. Multivariate logistic regression was used to determine risk factors associated with incident PICS. Of 238 eligible patients, 150 met all inclusion criteria and completed follow-up assessment. The incidence of PICS was 72

Neuroinflammation is one of crucial pathogenic mechanisms underlying Alzheimer's disease, sepsis-associated encephalopathy, and postoperative cognitive dysfunction. These diseases or conditions are often accompanied by typical clinical manifestations of cognitive impairments, including impaired learning and memory but underlying mechanisms are unknown. Hence, effective treatments are not available. In the current study, mice received intraperitoneal administrations of LPS (0.5 mg/kg, daily, Escherichia coliO55:B5) for seven consecutive days and after which, different cohorts were used for behavioral assessments with open field, Y maze, and novel object recognition test or for electrophysiology recordings of mEPSC, mIPSC or LTP in ex vivo preparations. Their hippocampi were harvested for immunostaining or Western blotting of PSD95, vGLUT1, vGAT, gephyrin, PV, and SST. In vivo optical fiber calcium recording was used to evaluate the neuronal excitability. During the early stage of neuroinflammation induced by LPS, there was a decrease of excitatory afferent synapses and transmission in the CA1. During the later stage of neuroinflammation, there was an increase of inhibitory afferent synapses and transmission in the CA1, resulting in excessive inhibition on excitatory neurons. Both of them contributed to the decreased hippocampal neuronal excitability and impaired LTP, ultimately leading to cognitive impairments. Overexpression of CREB in the early stage or inactivation of PV-positive interneurons in the later stage in the CA1 both improved cognitive impairments. Our work suggests that negating decreased excitatory and increased inhibitory afferent in the hippocampus may improve cognitive impairments relate to neuroinflammation associated with neurological diseases.

The autonomic nervous system (ANS) is essential for maintaining physiological homeostasis. Autonomic nervous system imbalance, characterised by sympathetic hyperactivation and low parasympathetic tone, can occur during the perioperative period. These changes drive systemic stress responses, cardiovascular instability, impaired tissue repair, and immunosuppression, which in turn increase infection risk, neurocognitive decline, and multiorgan dysfunction. Surgical trauma, anaesthesia, pain, hypothermia, and psychological stressors all contribute to this dysregulation, and consequently low parasympathetic tone results in the cholinergic anti-inflammatory pathway being less effective. High sympathetic nervous system activity promotes catecholamine surges and pro-inflammatory cytokine release. Pharmacological interventions, including dexmedetomidine and β-blockers, together with nonpharmacological strategies, such as electroacupuncture and temperature management, are measures that have potential to restore ANS balance. This systematic review covers ANS-mediated organ regulation, pathophysiological consequences of perioperative dysautonomia, and evidence-based therapeutic strategies. By integrating findings from multiple basic and clinical studies, the pivotal roles of ANS modulation in mitigating postoperative complications, including neurocognitive disorders, immunosuppression, and cancer recurrence, are discussed. Maintaining balance of the sympathetic and parasympathetic nervous systems is an important prospect in perioperative medicine that could benefit surgical patients' short- or long-term recovery.