[This corrects the article DOI: 10.3389/fnmol.2026.1798469.].

Electroacupuncture (EA) has been identified as an effective intervention for mitigating postoperative cognitive dysfunction in the elderly; however, its underlying mechanisms remain inadequately understood. This study aimed to elucidate the neuroprotective effects of EA on anesthesia/surgery-induced cognitive impairment in aged rats through a combination of behavioral testing, RNA sequencing analysis, Golgi-Cox staining, dendritic spine analysis, Sholl analysis, immunofluorescence assays, and western blot analysis. The findings demonstrated that EA ameliorates anesthesia/surgery-induced cognitive decline by inhibiting hippocampal synaptic dysfunction, with a notable enrichment in the downregulation of IL-17A signaling and upregulation of ERK signaling. Furthermore, the study confirmed that an exogenous increase in IL-17A expression can induce hippocampal synaptic dysfunction and partially negate the neuroprotective effects of EA by inhibiting the expression of the ERK/CREB signaling pathway. In conclusion, EA attenuates anesthesia/surgery-induced cognitive impairment in aged rats by inhibiting IL-17A-mediated hippocampal synaptic dysfunction via the ERK/CREB signaling pathway.

Sarcopenia (operationally defined as low skeletal muscle mass) and visceral obesity are both metabolic disorders associated with cognitive decline. Understanding the outcomes of these combined conditions is crucial. This study aimed to investigate how sarcopenia, measured by skeletal muscle index (SMI), and visceral obesity influence the occurrence of postoperative delirium (POD) in older adults. This was a prospective cohort study. A total of 270 patients undergoing total hip arthroplasty (THA) were enrolled. Sarcopenia was operationally defined as low skeletal muscle mass quantified by CT-based SMI, rather than the full EWGSOP2 definition. Visceral obesity was assessed by waist circumference (WC). POD was identified through the confusion assessment method (CAM). Receiver operating characteristic (ROC) curve analysis and the Youden index were used to calculate SMI thresholds for predicting POD. Participants were classified as follows: Group A: sarcopenia alone; Group B: visceral obesity alone; Group C: both sarcopenia and visceral obesity; and Group D: normal. We employed multivariate logistic regression model to estimate the correlation between sarcopenia, visceral obesity, and POD. A total of 270 patients were included. ROC analysis and the Youden index identified sex-specific SMI thresholds: < 29.55 cm2/m2 for males and < 23.62 cm2/m2 for females, optimizing SMI’s predictive accuracy for POD. The prevalence of POD was 64.70

BACKGROUND:Ultrasound-guided external oblique intercostal plane block (EOIPB) is a modified block technique used in the past few years for anterolateral upper abdominal wall analgesia. This study observed the efficacy of EOIPB in laparoscopic common bile duct exploration (LCBDE). OBJECTIVES:To evaluate the efficacy of EOIPB in patients undergoing LCBDE. METHODS:Sixty patients undergoing elective LCBDE were randomly assigned to two groups, an EOIPB group and a control group. In the EOIPB group, the patients received ultrasound-guided right EOIPB with a total of 20 mL of 0.5% ropivacaine before anesthesia induction. In the control group, the patients received no intervention before anesthesia induction. The primary outcomes were visual analog scale (VAS) scores within 24 h postoperatively and the number of patient-controlled analgesia (PCA) uses 24 h postoperatively. The secondary outcomes were dermatomal coverage of EOIPB, intraoperative vital signs, the intraoperative dose of remifentanil, and the 24-h postoperative quality of recovery-40 (QoR-40) score of the two groups. RESULTS:In the EOI group, VAS scores at rest and movement were significantly lower than in the control group at 30 min, 6 h, and 12 h postoperation (p < 0.05), with no significant difference at 24 h (p > 0.05). The number of PCA uses within 24 h was significantly lower in the EOIPB group (1.60 ± 0.89) compared to the control group (2.50 ± 1.11, p < 0.05). Dermatomal coverage in the EOIPB group achieved 100% T6-T10 at the anterior median and midclavicular lines, 100% T6-T9 at the anterior axillary line, and 93.3% T7-T8 at the posterior axillary line. Mean arterial pressure (MAP) was significantly lower in the EOIPB group at skin incision (T2), 10 min postoperative (T3), and 30 min after extubation (T5) (p < 0.05), and heart rate (HR) was significantly lower at T2 (p < 0.05). The intraoperative remifentanil dose was significantly reduced in the EOIPB group (0.84 ± 0.13 mg) compared to the control group (0.94 ± 0.14 mg, p < 0.05). The EOIPB group had a shorter bedridden time (23.33 ± 2.81 h vs. 25.23 ± 3.64 h, p < 0.05) and a higher QoR-40 score (170.6 ± 5.2 vs. 165.5 ± 6.3, p < 0.05), indicating improved recovery. CONCLUSION:The use of EOIPB in LCBDE can reduce VAS scores and the number of PCA uses 24 h postoperatively. EOIPB also steadied the intraoperative vital signs, reduced the dose of remifentanil, and improved the quality of recovery. EOIPB can be safely and effectively used in LCBDE.

Objective:Postoperative cognitive dysfunction (POCD), characterized by cognitive and memory decline following anesthesia and surgery, is a common complication in elderly patients. Nuclear factor erythroid-derived 2-like 2 (NRF2), a key regulator of cellular redox balance, has been implicated in cognitive processes in various neurological disorders. Electroacupuncture (EA), with its controllable stimulation parameters, has shown preventive effects against cognitive dysfunction. This study aimed to investigate whether NRF2 mediates the beneficial effects of EA on cognitive function in POCD. Methods:A POCD model was established in 20-month-old male Sprague-Dawley rats undergoing tibial fracture surgery. Beginning on postoperative day 24, EA was administered at the Hegu (LI4), Neiguan (PC6), and Zusanli (ST36) acupoints once daily for five consecutive days. The specific NRF2 antagonist ML385 (30 mg/kg) was intraperitoneally administered 2 hours before each EA session over the same period. Behavioral tests, including the T-maze test, fear conditioning (FC), and novel object recognition (NOR), were conducted on postoperative day 30. Immunofluorescence staining was used to assess neuronal count, apoptosis, microglial activation, and the percentage of NRF2-positive microglia. Electrophysiological recordings of brain activity were also performed. Results:EA treatment significantly improved cognitive and memory performance in POCD rats. Immunofluorescence analysis revealed reduced neuronal apoptosis, increased synaptic density, suppressed microglial activation, and enhanced nuclear translocation of NRF2, indicating attenuated neuroinflammation and oxidative stress. Furthermore, EA strengthened the phase-amplitude coupling between theta and gamma oscillations. Notably, all these neuroprotective and cognitive-enhancing effects of EA were abolished by ML385. Conclusion:In a POCD rat model, our findings demonstrate that EA ameliorates cognitive impairment, and this effect is potentially mediated through NRF2 pathway activation.

We developed and externally validated an interpretable machine-learning model for observed continuous renal replacement therapy (CRRT) initiation in sepsis-associated acute kidney injury (SA-AKI) using a strict 24-hour landmark framework. This multicenter retrospective study used MIMIC-IV and eICU-CRD data. Predictors were restricted to the period from sepsis diagnosis to 24 h, and the outcome was first observed CRRT initiation after the landmark and within 7 days. Patients who died, initiated CRRT, or were no longer under observation by 24 h were excluded. Eight algorithms were evaluated, and a seven-predictor Gradient Boosting model was selected. Discrimination, calibration, incremental value, SHAP-based interpretation, and exploratory prediction-subgroup outcomes were assessed. The final MIMIC-IV cohort included 5,238 patients, with 239 CRRT events; 3,666 were assigned to training and 1,572 to internal validation. The eICU-CRD cohort included 4,683 patients and 157 events. The model retained serum creatinine, AKI stage, SOFA score, urine output, lactate, red blood cell distribution width, and peripheral oxygen saturation. AUCs were 0.905 internally and 0.816 externally, with an external calibration slope of 0.567. In an exploratory age- and sex-matched eICU analysis, the high predicted-risk/no observed CRRT subgroup had higher ICU, 7-day, and 28-day mortality than the true-negative subgroup. The model provided interpretable risk estimates for observed CRRT initiation, but external calibration and incremental value were limited. Findings should not be interpreted as evidence of CRRT indication, undertreatment, or treatment benefit. Prospective validation and local recalibration are required.

Diabetes mellitus significantly impacts perioperative anesthetic management. Patients with diabetic neuropathy exhibit increased sensitivity to local anesthetics, yet the underlying mechanisms, particularly regarding the median effective dose (ED50) of ropivacaine and the role of voltage-gated sodium channels (Navs), remain incompletely elucidated. This study investigated the role of Navs in mediating the ED50 of ropivacaine in streptozotocin (STZ)-induced diabetic rats. Using the Dixon up-and-down method, the ED50 for sciatic nerve motor block was significantly lower in diabetic rats (0.100%) than in controls (0.142%), indicating heightened local anesthetic sensitivity. This pharmacodynamic shift was associated with underlying neuropathic changes, including reduced motor nerve conduction velocity (MNCV), decreased axon density, and downregulated expression of key Nav subtypes (Nav1.7, Nav1.8, Nav1.9) and the contactin-associated protein (CASPR) in the sciatic nerve and dorsal root ganglia (DRG). Crucially, administration of ropivacaine at the identified ED50 dose did not exacerbate neurophysiological dysfunction, histological damage, or alter Navs/CASPR expression in diabetic nerves compared with saline-treated diabetic group, demonstrating a favorable safety profile. These findings elucidate the mechanism underlying reduced local anesthetic requirements in diabetic neuropathy, which involves Navs downregulation and structural nerve alterations, and support the clinical use of lower, effective ropivacaine doses in diabetic patients to achieve successful analgesia without increasing neurotoxicity risk.

Patients undergoing total knee arthroplasty (TKA) may suffer from perioperative sleep disorders (PSD), and their management is challenging. The aim of this study was to assess the efficiency of digital cognitive behavioral therapy (dCBT) in the management of PSD after TKA. From December 2022 to August 2023, a total of 114 patients undergoing primary, unilateral TKA under general anaesthesia were included. The primary outcome was the Athens Insomnia Scale (AIS) score. Other outcome parameters included sleep quality, pain scores (NRS scores), mental disorders (hospital anxiety and depression scale scores and MMSE scores) and recovery quality (quality of recovery-40 questionnaire). There was no significant difference in AIS score, sleep quality, pain score or mental status between the two groups immediately after admission. The AIS scores of the dCBT group and control group were 3 (2) andvs. 3 (2.25) (P < 0.05) on the first postoperative day, 3 (1) vs. 3 (3) (P < 0.05) on the third postoperative day, and 1 (1) vs. 2 (2) (P < 0.05) on the 15th postoperative day, respectively. Compared with those in the control group, the sleep quality, anxiety scores and recovery quality in the early stage significantly improved in the dCBT group. However, the pain scores and cognitive function of the two groups were not significantly different. dCBT can decrease the severity of PSD and improve recovery quality in the early stage after TKA surgery. Furthermore, dCBT can relieve anxiety and thereby promote postoperative recovery.

Purpose:This retrospective study aimed to explore the effect of erector spinae plane block (ESPB) on the gastrointestinal function in patients after traumatic lumbar fracture surgery and the effects of different levels of block approach. Patients and Methods:Clinical data were retrospectively analyzed from electronic medical records of patients who underwent traumatic lumbar spine fracture surgery (September 2022-June 2023). Eligible patients were divided into three groups: group L (bilateral ESPB at L3 level), group T (bilateral ESPB at T12 level) and group C (no block). The primary outcomes were the incidence and the time of occurrence postoperative bloating. We also recorded the time of the first flatus and bowel movement, postoperative nausea and vomiting (PONV), gastrointestinal medications, enema, intraoperative opioid dosage, number of rescue analgesia within 48 h postoperatively, visual analogue scale (VAS) scores at 24 h and 48 h postoperatively, inflammatory mediators, complications and hospital length of stay (LOS). Results:145 patients were included, including 32 in group L, 33 in group T and 80 in group C. Patients in group L and T experienced less bloating compared to group C (P < 0.05). Patients in group T presented bloating significantly later than group L (log rank P < 0.0167). Patients in group L and group T had a significantly shorter time to first flatus and bowel movement, lower incidence of PONV, gastrointestinal medications and enema, and a lower dose of opioid and VAS scores at 24 h postoperatively compared to group C (all P < 0.05), the difference between group L and T was not statistically significant. Conclusion:Bilateral ESPB improved postoperative gastrointestinal function in patients with traumatic lumbar spine fracture, where the T12 level of ESPB was more favorable than the L3 level.

Postoperative cognitive dysfunction (POCD) occurs in elderly surgical patients as a common complication and manifests as cognitive decline. It is associated with neuroinflammation, microglial activation, and impaired metabolic waste clearance-key mechanisms underlying POCD. Meningeal lymphatic vessels (MLVs) facilitate the drainage of cerebrospinal fluid (CSF) and interstitial fluid (IF), regulating brain immune responses and clearing metabolic waste, immune cells, and antigens, thus modulating neuroinflammation. This study investigates whether enhancing meningeal lymphatic drainage mitigates POCD in aged mice. A POCD mouse model was established via tibial fracture surgery under general anesthesia. Meningeal lymphatic drainage was assessed using immunofluorescence, followed by intra-cisterna magna injection of adeno-associated virus (AAV)-vascular endothelial growth factor-c (AAV-VEGF-C) or AAV-mCherry. Cognitive performance, microglial activation, and pro-inflammatory cytokines were evaluated through behavioral tests, western blotting, and immunofluorescence. Anesthesia and surgery impair the function and morphology of MLVs, leading to reduced lymphatic drainage. These changes were associated with elevated hippocampal expression of microglial activation markers ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation 68 (CD68), as well as increased levels of Interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), which collectively contributed to cognitive impairment. In contrast, AAV-VEGF-C enhanced meningeal lymphatic drainage by promoting lymphangiogenesis and improving function, reduced microglial activation and neuroinflammation, and improved cognitive outcomes. These findings demonstrate that dysfunction of MLVs exacerbates POCD by amplifying neuroinflammation, while enhancing the function of MLVs mitigates these effects. MLVs represent a promising therapeutic target for managing POCD among the aged.

Perioperative neurocognitive disorders (PND), characterized by persistent cognitive impairment lasting from days to years, present substantial clinical challenges in elderly surgical populations, profoundly compromising functional independence, quality of life, and long-term prognosis. We aimed to investigate the effects of short-chain fatty acids (SCFAs) treatment on PND via mediating Brain-derived neurotrophic factor (BDNF)/Phosphatidylinositol3-kinase (PI3K)/Protein kinase B (Akt) pathway. Using 16S rDNA sequencing targeting the V3–V4 hypervariable regions, we first demonstrated significant gut microbiota dysbiosis in PND model rats, accompanied by altered SCFAs profiles. Subsequent fecal microbiota transplantation (FMT) experiments established causal relationships between PND-associated microbial alterations and spatial cognitive deficits. Mechanistically, SCFAs supplementation attenuated neuronal damage and restored synaptic plasticity, as evidenced by Nissl staining quantification (reduced chromatolysis), TUNEL assay (decreased apoptosis rate), and immunohistochemical analysis (upregulated NeuN expression). Molecular investigations revealed that SCFAs-mediated cognitive improvement involved BDNF upregulation and subsequent PI3K/Akt pathway activation, ultimately enhancing neuronal survival and synaptic integrity. Notably, PND animals exhibited characteristic neuropathological features including synaptic density reduction (PSD-95 downregulation), neuroinflammation amplification (IL-6 elevation), and apoptosis activation—all significantly reversed by SCFA intervention. Our findings establish a novel gut-brain axis mechanism wherein microbiota-derived SCFAs may exert neuroprotection through BDNF-dependent PI3K/Akt signaling, and offer potential therapeutic strategies for PND management. Anesthesia and surgery-induced neuronal damage, accompanied by reduced dendritic spine density and PSD-95 levels, are key contributors to PND. Furthermore, SCFAs appear to alleviate these pathophysiological changes through the BDNF/PI3K/Akt pathway, thereby improving cognitive performance.

Regular physical activity has been shown to ameliorate cognitive decline associated with aging, and to improve autonomic nervous function. However, the effect of active housework, a form of light to moderate physical activity, on postoperative cognitive function in the elderly remain unknown. The aim of this study is to investigate whether active housework exerts a protective effect against delayed neurocognitive recovery (dNCR), and to explore the role of vagal activity in this relationship. This is a prospective nested case-control study that enrolled 152 elderly patients scheduled for elective knee replacement surgery. The neuropsychological assessments were conducted to evaluate dNCR both preoperatively and one week postoperatively. Physical activity levels were quantified based on the Physical Activity Scale for the Elderly and categorized into active housework and sedentary behavior groups using hierarchical clustering. High-frequency spectral analysis of heart rate variability was used to assess vagal activity. Multivariable logistic regression analysis was employed to examine the association between active housework, vagal activity, and dNCR. Additionally, mediation analysis was performed to explore the possible mediating effect of vagal activity. dNCR occurred in 33/141 (23.4

Purpose: Patients undergoing arthroscopic hip surgery (AHS) require good analgesia and early rehabilitation after surgery, and there is no consensus on the optimal nerve block. We aimed to compare the efficacy of the pericapsular nerve group (PENG) block with lateral femoral cutaneous nerve (LFCN) block compared to fascia iliaca compartment block (FICB) in patients with AHS. Patients and Methods: A total of 80 patients receiving AHS under general anesthesia were randomized to receive either FICB (group F) or PENG block in combination with LFCN block (group P). The primary outcomes were the rate of quadriceps weakness after block on the afflicted side, as well as muscle strength grading and pain score after block, and the quality of recovery on the second postoperative day. Results: Compared with group F, group P had a lower incidence of quadriceps weakness 48 h after block (76.9% vs 28.2%, P < 0.001), and had less impact on muscle strength grade and lower static pain score at 6, 12, 18, 24, 36, and 48 h after block (P < 0.001), and a lower dynamic pain score at 6 and 12 h after block in group P ( p < 0.05). The quality of recovery on the second postoperative day improved ( p < 0.05). Conclusion: In comparison to FICB, PENG block in combination with LFCN block can affect less quadriceps muscle strength and reduce the use of postoperative analgesics, which is beneficial for the postoperative recovery of AHS patients.

Cognitive impairment is a major complication of cerebral ischemia–reperfusion (CIR) injury and has an important impact on the quality of life of patients. However, the precise mechanisms underlying cognitive impairment after CIR injury remain elusive. In the current study, we investigated the role of interleukin 17 A (IL-17A) on CIR injury-induced cognitive impairment in wild-type and IL-17A knockout mice using RNA sequencing analysis, neurological assessments, Golgi–Cox staining, dendritic spine analysis, immunofluorescence assay, and western blot analysis. RNA sequencing identified 195 CIR-induced differentially expressed genes (83 upregulated and 112 downregulated), highlighting several enriched biological processes (negative regulation of phosphorylation, transcription regulator complex, and receptor ligand activity) and signaling pathways (mitogen-activated protein kinase [MAPK], tumor necrosis factor, and IL-17 signaling pathways). We also injected adeno-associated virus into the bilateral hippocampal CA1 regions of CIR mice to upregulate or downregulate cyclic AMP response element-binding protein. IL-17A knockout activated the extracellular signal-regulated kinase (ERK)/MAPK signaling pathway and further improved synaptic plasticity, structure, and function in CIR mice. Together, our findings suggest that IL-17A deficiency alleviates CIR injury by activating the ERK/MAPK signaling pathway and enhancing hippocampal synaptic plasticity.

ABSTRACT Purpose This study aims to explore the neuroprotective effect of propofol in improving traumatic brain injury (TBI) by inhibiting ferroptosis through the modulation of the endothelial nitric oxide (NO) synthase (eNOS)/NO signaling pathway. Methods The GSE173975 dataset was used to analyze the differentially expressed genes between TBI and sham surgery control groups in the short and long term. A TBI model was established in 2‐month‐old male SPF C57BL/6 mice by impact exposure of the exposed dura mater. After the establishment of the TBI model, propofol (30 mg/kg) or saline was administered via intraperitoneal injection for intervention. Nissl staining and Perls staining were employed to assess neuronal function and iron deposition, respectively. Western blot technology was employed to detect the expression of proteins related to ferroptosis. Immunofluorescence staining of astrocytes and microglia was utilized to assess the neuroinflammatory response induced by TBI. The Morris water maze (MWM) and novel object recognition (NOR) tests were employed to assess cognitive dysfunction induced by TBI. Findings Bioinformatics analysis revealed aberrant gene expression associated with iron transport, neuronal death, and inflammatory response in the initial stages of TBI. Long‐term abnormalities were predominantly linked to genes involved in inflammatory response. Perls staining and protein expression analysis confirmed the occurrence of iron deposition and ferroptosis following TBI. Propofol treatment significantly reduced iron deposition and ferroptosis induced by TBI. Nissl staining demonstrated enhanced neuronal function, while TUNEL staining indicated reduced neuronal apoptosis. Immunofluorescence analysis demonstrated that propofol significantly reduced the proliferation of astrocytes and activation of microglia induced by TBI in the long term. The results of MWM and NOR tests indicated that propofol significantly improved the long‐term cognitive dysfunction induced by TBI. Propofol exerts neuroprotective effects by increasing the expression of eNOS protein and the content of NO. The neuroprotective effects of propofol can be reversed by the eNOS inhibitor L‐NAME. Conclusion Propofol significantly improves the prognosis of TBI by inhibiting ferroptosis through the modulation of the eNOS/NO signaling pathway. The study results provide a scientific basis for the clinical use of propofol as a neuroprotective agent and offer a new direction for the development of new treatment strategies for TBI.

Alzheimer's disease (AD) is a severe neurological illness that causes memory loss and is a global problem. The calcium hypothesis recently steadily evolved in AD. The prospective targets for calcium homeostasis therapy, however, are limited, and gene expression-level research connected to calcium homeostasis in AD remains hazy. In this study, we analyzed the microarray dataset (GSE132903) taken from the Gene Expression Omnibus (GEO) database to investigate calcium homeostasis-related genes for AD. Using immunoblot analysis, we examined the association of ITPKB with inflammation in AD. Additionally, the immunofluorescence technique was employed to assess the impact of pharmacological inhibition of ITPKB on the amyloid-β (Aβ) plaque deposition in APP/PS1 mice. This article's further exploration of calcium homeostasis-related genes has propelled the validation of the calcium homeostasis theory in AD.

OBJECTIVE:This study aimed to identify risk factors associated with hypotension in patients undergoing total knee arthroplasty (TKA) under spinal anesthesia. METHOD:A total of 200 patients (50-75 years of age) who underwent elective TKA under spinal anesthesia between October 2023 and January 2024 were enrolled. Patients were divided into two groups (hypotensive and nonhypotensive) depending on the occurrence of postspinal anesthesia hypotension (PSAH). Patient characteristics (age, sex, body mass index, and medical history), blood pressure, heart rate, and ultrasound data before anesthesia were documented. Multivariate logistic regression models were used to determine risk factors for hypotension after spinal anesthesia. Furthermore, a nomogram was constructed according to independent predictive factors. The area under the curve (AUC) and calibration curves were employed to assess the performance of the nomogram. RESULTS:In total, 175 patients were analyzed and 79 (45.1%) developed PSAH. Logistic regression analysis revealed that variability of the inferior vena cava (odds ratio, OR, 1.147; 95% confidence interval, CI: 1.090-1.207; p < 0.001) and systolic arterial blood pressure (SABP, OR 1.078; 95% CI: 1.043-1.115; p < 0.001) were independent risk factors for PSAH. Receiver operating characteristic (ROC) curve analysis showed that the AUC of the inferior vena cava collapsibility index (IVCCI) and SABP alone were 0.806 and 0.701, respectively, while the AUC of both combined was 0.841. Specifically, an IVCCI of > 37.5% and systolic arterial blood pressure of > 157 mm Hg were considered threshold values. Furthermore, we found that the combination had a better predictive value with higher AUC value, sensitivity, and specificity than the index alone. The nomogram model and calibration curves demonstrated the satisfactory predictive performance of the model. CONCLUSION:Elevated preoperative systolic arterial blood pressure and a higher IVCCI were identified as independent risk factors for hypotension in patients receiving spinal anesthesia, which may help guide personalized treatment.

Background: Alzheimer’s disease (AD) is the most common sort of neurodegenerative dementia, characterized by its challenging, diverse, and progressive nature. Despite significant progress in neuroscience, the current treatment strategies remain suboptimal. Objective: Identifying a more accurate molecular target for the involvement of microglia in the pathogenic process of AD and exploring potential mechanisms via which it could influence disease. Methods: We utilized single-cell RNA sequencing (scRNA-seq) analysis in conjunction with APP/PS1 mouse models to find out the molecular mechanism of AD. With the goal of investigating the cellular heterogeneity of AD, we downloaded the scRNA-seq data from the Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs). Additionally, we evaluated learning and memory capacity using the behavioral experiment. We also examined the expression of proteins associated with memory using western blotting. Immunofluorescence was employed to investigate alterations in amyloid plaques and microglia. Results: Our findings revealed an upregulation of ITGAX expression in APP/PS1 transgenic mice, which coincided with a downregulation of synaptic plasticity-related proteins, an increase in amyloid-β (Aβ) plaques, and an elevation in the number of M1 microglia. Interestingly, deletion of ITGAX resulted in increased Aβ plaque deposition, a rise in the M1 microglial phenotype, and decreased production of synaptic plasticity-related proteins, all of which contributed to a decline in learning and memory. Conclusions: This research suggested that ITGAX may have a beneficial impact on the APP/PS1 mice model, as its decreased expression could exacerbate the impairment of synaptic plasticity and worsen cognitive dysfunction.

Delayed neurocognitive recovery (dNCR) can result in unfavorable outcomes in elderly surgical patients. Physical activity (PA) has been shown to improve cognitive function, potentially by reducing systemic inflammatory responses. However, there is a lack of supportive data indicating whether PA has a protective effect against dNCR. To examine the correlation between dNCR and PA, and to further analyze if pro-inflammatory cytokines mediate this relationship. This study is a prospective nested case-control investigation of elderly patients who had knee replacement surgery. dNCR was defined as a decline in cognitive function compared with baseline by using a battery of neuropsychological tests. PA was assessed with the Physical Activity Scale for the Elderly (PASE). Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of IL-6, IL-1β, and TNF-α. Multivariable logistic regression analysis was conducted to assess the association between PA and dNCR. Mediation analysis was employed to evaluate whether pro-inflammatory cytokines mediate the relationship between them. A cohort of 152 patients was included, resulting in an incidence rate of dNCR of 23.68 www.http://chictr.org.cn , Registration No. ChiCTR2300070834, Registration date: April 24, 2023.