Surgery Versus Endovascular Treatment for Proximal Anterior Cerebral Artery Aneurysms: A Meta-Analysis.

BACKGROUND: Proximal anterior cerebral artery (PACA) aneurysms account for less than 1% of all intracranial aneurysms. These aneurysms possess a challenge to surgeons due to their small size, wide base, fragile wall, and accompanying vascular anomalies. Surgery and endovascular treatment are both effective treatment options for PACA aneurysms but there is currently no consensus on which is the method of choice. OBJECTIVE: A systematic review and meta-analysis was conducted to investigate treatment strategies for aneurysms at proximal anterior cerebral artery. MATERIAL AND METHODS: The Cochrane Library, EMBASE, PubMed, and Web of Science databases were systematically searched for studies published between January 01, 2000 and December 01, 2020 that investigated surgery and/or endovascular treatment for patients with PACA. RESULTS AND CONCLUSIONS: Nineteen retrospective studies involving 358 patients met the inclusion criteria. Among these patients, 150 were treated surgically and 208 were treated using an endovascular technique. Preoperative morbidity was significantly greater in the surgical patients compared with the endovascular treated patients but there was no difference between groups in procedural related morbidity. The rates of favorable clinical outcome at time of discharge and at follow-up were statistically significantly greater in the endovascular group compared with the surgical group. Procedural related mortality was 8.7% for the surgical group and 1% in the endovascular group. In summary, our meta-analysis emphasized the safety and efficiency of endovascular treatment, and concluded that it was superior to surgery in acquiring favorable clinical outcome and reducing the perioperative complications. However, surgery was still the preferred treatment strategy for ruptured PACA aneurysms. Preoperative evaluation seems to be of great vital.

Hexokinase 2 nonmetabolic function-mediated phosphorylation of IκBα enhances pancreatic ductal adenocarcinoma progression.

Aberrant signaling in tumor cells induces nonmetabolic functions of some metabolic enzymes in many cellular activities. As a key glycolytic enzyme, the nonmetabolic function of hexokinase 2 (HK2) plays a role in tumor immune evasion. However, whether HK2, dependent of its nonmetabolic activity, plays a role in human pancreatic ductal adenocarcinoma (PDAC) tumorigenesis remains unclear. Here, we demonstrated that HK2 acts as a protein kinase and phosphorylates IκBα at T291 in PDAC cells, activating NF-κB, which enters the nucleus and promotes the expression of downstream targets under hypoxia. HK2 nonmetabolic activity-promoted activation of NF-κB promotes the proliferation, migration, and invasion of PDAC cells. These findings provide new insights into the multifaceted roles of HK2 in tumor development and underscore the potential of targeting HK2 protein kinase activity for PDAC treatment.

High-Risk Hepatocellular Carcinoma: Hepatic Arterial Infusion Chemotherapy versus Transarterial Chemoembolization.

Objective: To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with transarterial chemoembolization (TACE) for the treatment of high-risk hepatocellular carcinoma (hHCC) patients. Methods: Between January 2014 and August 2022, a total of 1765 consecutive patients with hHCC who underwent initial intra-arterial therapies were reviewed and divided into a TACE group (n, 507) and a HAIC group (n, 426). The study used propensity score matching (PSM) to reduce selectivity bias. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan‒Meier curves with the Log rank test. The objective response rate (ORR), conversion surgery rate (CSR) adverse event (AE) comparison and subgroup analysis were performed between the two groups. Results: After PSM 1:1, 444 patients were divided into two groups. The patients with hHCC who received HAIC had higher median PFS (6.1 vs 3.3 months, P < 0.001) and OS (10.3 vs 8.2 months, P=0.303) than TACE. Higher ORR (24.8% vs 11.7%) and CSR (15.5% vs 8.9%) were found in the HAIC group than in the TACE group (both P < 0.05). The incidence of grade 3/4 AE was 23.9% and 8.1% in the TACE and HAIC groups, respectively. The subgroup analysis suggest that HAIC appeared to particularly benefit patients with tumor diameter of more than 10 centimeters (hazard ratio [HR], 0.6; 95% CI, 0.47-0.77; p, 0.00) and PVTT Vp4 (HR, 0.56; 95% CI, 0.39-0.8; P, 0.01) for PFS outperforming TACE. Conclusion: HAIC can provide better disease control for hHCC than cTACE, with a comparable long-term OS and safety.

Integrative Analysis of PAIP2B to Identify a Novel Biomarker for Pancreatic Ductal Adenocarcinoma.

The aim of the study was to evaluate the potential diagnostic and prognostic value of gene, Poly A-Binding Protein Interacting Protein 2B ( PAIP2B ) in pancreatic cancer. We used the gene expression data and clinical information of pancreatic adenocarcinoma patients from The Cancer Genome Atlas database and Gene Expression Omnibus database to analyze the expression of PAIP2B in pancreatic cancer samples, and validated the expression of PAIP2B in tumor tissue, using bioinformatics technology to explore the prognostic value of PAIP2B and its possible biological function. A significantly lower level of PAIP2B was observed in pancreatic cancer patients than in controls, and validated by immunohistochemistry. PAIP2B reduced the proliferation and invasion of cancer cells and had a significantly high expression in early stage. Patients with lower levels of PAIP2B had a significantly shorter median survival time than those with higher levels. DNA demethylation played an important role in PAIP2B expression. In addition, PAIP2B expression was significantly associated with the tumor-infiltrating immune cells, especially T cells CD8, T cells CD4 memory resting, macrophages M0, and dendritic cells resting. Our study also found that PAIP2B regulated miRNA function leading to disease progression in pancreatic cancer patients. Our study explored the potential value of PAIP2B as a biological link between prognosis and pancreatic cancer, and provided reference for the follow-up study on the role of PAIP2B in pancreatic cancer.

Identification of host gene-microbiome associations in colorectal cancer patients using mendelian randomization.

BACKGROUND: There are many studies indicating that alterations in the abundance of certain gut microbiota are associated with colorectal cancer (CRC). However, a causal relationship has not been identified due to confounding factors such as lifestyle, environmental, and possible reverse causal associations between the two. Furthermore, certain host gene mutations can also contribute to the development of CRC. However, the association between genes and gut microbes in patients with CRC has not been extensively studied. METHODS: We conducted a two-sample Mendelian randomization (MR) study to reveal the causal relationship between gut microbiota and CRC. We obtained SNPs associated with gut microbiome abundance as instrumental variables (IVs) from a large-scale, multi-ethnic GWAS study, and extracted CRC-related datasets from an East Asian Population genetic consortia GWAS (AGWAS) study and FinnGen consortium, respectively. We analyzed a total of 166 bacterial features at four taxonomic levels, including order, family, genus, and species. The inverse-variance-weighted (IVW), weighted median, MR-Egger, and simple median methods were applied to the MR analysis, and the robustness of the results were tested using a series of sensitivity analyses. We extracted IVs of gut microbiota with direct causal association with CRC for SNP annotation to identify the genes in which these genetic variants were located to reveal the possible host gene-microbiome associations in CRC patients. RESULTS: The findings from our MR analysis based on CRC-associated GWAS datasets from AGWAS revealed causal relationships between 6 bacterial taxa and CRC at a locus-wide significance level (P < 1 × 10-5). The IVW method found that family Porphyromonadaceae, genera Anaerotruncus, Intestinibacter, Slackia, and Ruminococcaceae UCG004, and species Eubacterium coprostanoligenes group were positively associated with CRC risk, which was generally consistent with the results of other complementary analyses. The results of a meta-analysis of the MR estimates from the AGWAS and the FinnGen datasets showed that family Porphyromonadaceae and genera Slackia, Anaerotruncus, and Intestinibacter replicated the same causal association. Sensitivity analysis of all causal associations did not indicate significant heterogeneity, horizontal pleiotropy, or reverse causal associations. We annotated the SNPs at a locus-wide significance level of the above intestinal flora and identified 24 host genes that may be related to pathogenic intestinal microflora in CRC patients. CONCLUSION: This study supported the causal relationship of gut microbiota on CRC and revealed a possible correlation between genes and pathogenic microbiota in CRC. These findings suggested that the study of the gut microbiome and its further multi-omics analysis was important for the prevention and treatment of CRC.

Risk prediction of second primary malignancies after gynecological malignant neoplasms resection with and without radiation therapy: a population-based surveillance, epidemiology, and end results (SEER) analysis.

PURPOSE: The association between post-resection radiotherapy for primary gynecological malignant neoplasms (GMNs) and the development of secondary primary malignancies (SPMs) remains a subject of debate. This study represents the first population-based analysis employing a multivariate competitive risk model to assess risk factors for this relationship and to develop a comprehensive competing-risk nomogram for quantitatively predicting SPM probabilities. MATERIALS AND METHODS: In our study, data on patients with primary GMNs were retrospectively collected from the Epidemiology, Surveillance and End Results (SEER) database from 1973 to 2015. The incidence of secondary malignant tumors diagnosed at least six months after GMN diagnosis was compared to determine potential risk factors for SPMs in GMN patients using the Fine and Gray proportional sub-distribution hazard model. A competing-risk nomogram was constructed to quantify SPM probabilities. RESULTS: A total of 109,537 patients with GMNs were included in the study, with 76,675 and 32,862 GMN patients in the training and verification sets, respectively. The competing-risk model analysis identified age, primary tumor location, tumor grade, disease stage, chemotherapy, and radiation as risk factors for SPMs in GMN patients. Calibration curves and ROC curves in both training and verification cohorts demonstrated the predictive accuracy of the established nomogram, which exhibited a good ability to predict SPM occurrence. CONCLUSIONS: This study presents the nomogram developed for quantitatively predicting SPM probabilities in GMN patients for the first time. The constructed nomogram can assist clinicians in designing personalized treatment strategies and facilitate clinical decision-making processes.

Comparison of the efficacy and safety of third-line treatments for advanced gastric cancer: A systematic review and network meta-analysis.

Background: Many options for third-line treatment of advanced gastric cancer (GC) or gastroesophageal junction carcinoma (GEJC) have been developed. Therapies including immunotherapy (nivolumab), chemotherapy (irinotecan, FTD/TPI), targeted therapy (apatinib), and antibody drug conjugates (ADC) have shown to increase the survival rates in patients, but few studies have compared the relative efficacy of these treatments. Here, we compared the efficacies of these regimens using network meta-analysis (NMA) to provide guides in selecting the best regimen and formulating a precise individualized treatment plan. Methods: The published RCTs of phase II/III in PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched. The median overall survival (mOS) was the primary outcome of NMA, and the other outcomes were median progression-free survival (mPFS), disease control rate (DCR) (proportion of patients with confirmed CR, PR, or stable disease (SD)) and incidence of grade 3 or above adverse events (≥3AEs). Results: Five phase II/III RCTs involving 1674 patients and 7 treatment regimens were analyzed. It showed that Trastuzumab Deruxtecan (DS-8201) prolonged the OS of patients significantly comparing with chemotherapy (HR: 0.59; 95% CI: 0.39-0.89) for the overall population. DS-8201 (HR: 0.27; 95% CI: 0.17-0.42) and chemotherapy (HR: 0.57; 95% CI: 0.47-0.7) improved the PFS significantly over nivolumab. Apatinib (RR: 3.04; 95% CI: 1.65-5.95) and DS-8201 (RR: 2.67; 95% CI: 1.51-4.83) were more effective than nivolumab in improving DCR. DS-8201 achieved greater OS benefits compared to chemotherapy (HR: 0.59; 95% CI: 0.39-0.88) for patients who were HER2-positive. We ranked the Bayesian surface under the cumulative ranking curve according to OS benefit, and showed that ADC ranked first for the general patient population and for patients with a HER2-positive diagnosis, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. For patients with GEJC, nivolumab ranked first. Conclusions: Nivolumab, apatinib, chemotherapy, and ADC all improved the OS of GC/GEJC patients significantly. ADC may be the best option for the overall population of GC, as well as for patients with HER2-overexpression, intestinal histopathology, previous gastrectomy history, gastric origination cancer, ages over 65 and ECOG PS=0/1, followed by nivolumab and apatinib. Nivolumab may be the first treatment option for GEJC patients. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022364714.

Posterior division of ipsilateral C7 transfer to C5 for shoulder abduction limitation.

Background: Reparation of C5 by proximal selective ipsilateral C7 transfer has been reported for the treatment of neurogenic shoulder abduction limitation as an alternative to the reparation of the suprascapular nerve (SSN) and the axillary nerve (AXN) by distal nerve transfers. However, there is a lack of evidence to support either strategy leading to better outcomes based on long-term follow-up. Objective: The purpose of the study was to investigate the safety and long-term outcomes of the posterior division of ipsilateral C7 (PDIC7) transfer to C5 in treating neurogenic shoulder abduction limitation. Methods: A total of 27 cases with limited shoulder abduction caused by C5 injury (24 cases of trauma, 2 cases of neuritis, and 1 case of iatrogenic injury) underwent PDIC7 transfer to the C5 root. A total of 12 cases (11 cases of trauma and 1 case of neuritis) of C5 injury underwent spinal accessory nerve (SAN) transfer to SSN plus the triceps muscular branch of the radial nerve (TMBRN) transfer to AXN. The patients were followed up for at least 12 months for muscle strength and shoulder abduction range of motion (ROM). Results: In cases that underwent PDIC7 transfer, the average shoulder abduction was 105.9° at the 12-month follow-up. In total, 26 of 27 patients recovered at least M3 (13 reached M4) (Medical Research Council Grading) of the deltoid. In cases that underwent SAN transfer to SSN plus TMBRN to AXN, the average shoulder abduction was 84.6° at the 12-month follow-up. In total, 11 of 12 patients recovered at least M3 (4 reached M4) of the deltoid. Conclusion: Posterior division of ipsilateral C7 transfer is a one-stage, safe, and effective surgical procedure for patients with neurogenic shoulder abduction limitation.

Ablation of NLRP3 inflammasome attenuates muscle atrophy via inhibiting pyroptosis, proteolysis and apoptosis following denervation.

Rationale: The inflammasome has been widely reported to be involved in various myopathies, but little is known about its role in denervated muscle. Here, we explored the role of NLRP3 inflammasome activation in experimental models of denervation in vitro and in vivo. Methods: Employing muscular NLRP3 specific knock-out (NLRP3 cKO) mice, we evaluated the effects of the NLRP3 inflammasome on muscle atrophy in vivo in muscle-specific NLRP3 conditional knockout (cKO) mice subjected to sciatic nerve transection and in vitro in cells incubated with NLRP3 inflammasome activator (NIA). To evaluate the underlying mechanisms, samples were collected at different time points for RNA-sequencing (RNA-seq), and the interacting molecules were comprehensively analysed. Results : In the experimental model, NLRP3 inflammasome activation after denervation led to pyroptosis and upregulation of MuRF1 and Atrogin-1 expression, facilitating ubiquitin-proteasome system (UPS) activation, which was responsible for muscle proteolysis. Conversely, genetic knockout of NLRP3 in muscle inhibited pyroptosis-associated protein expression and significantly ameliorated muscle atrophy. Furthermore, cotreatment with shRNA-NLRP3 markedly attenuated NIA-induced C2C12 myotube pyroptosis and atrophy. Intriguingly, inhibition of NLRP3 inflammasome activation significantly suppressed apoptosis. Conclusions: These in vivo and in vitro findings demonstrate that during denervation, the NLRP3 inflammasome is activated and stimulates muscle atrophy via pyroptosis, proteolysis and apoptosis, suggesting that it may contribute to the pathogenesis of neuromuscular diseases.

EID3 Promotes Glioma Cell Proliferation and Survival by Inactivating AMPKα1.

OBJECTIVE: EID3 (EP300-interacting inhibitor of differentiation) was identified as a novel member of EID family and plays a pivotal role in colorectal cancer development. However, its role in glioma remained elusive. In current study, we identified EID3 as a novel oncogenic molecule in human glioma and is critical for glioma cell survival, proliferation and invasion. METHODS: A total of five patients with glioma were recruited in present study and fresh glioma samples were removed from patients. Four weeks old male non-obese diabetic severe combined immune deficiency (NOD/SCID) mice were used as transplant recipient models. The subcutaneous tumor size was calculated and recorded every week with vernier caliper. EID3 and AMP-activated protein kinase α1 (AMPKα1) expression levels were confirmed by real-time polymerase chain reaction and Western blot assays. Colony formation assays were performed to evaluate cell proliferation. Methyl thiazolyl tetrazolium (MTT) assays were performed for cell viability assessment. Trypan blue staining approach was applied for cell death assessment. Cell Apoptosis DNA ELISA Detection Kit was used for apoptosis assessment. RESULTS: EID3 was preferentially expressed in glioma tissues/cells, while undetectable in astrocytes, neuronal cells, or normal brain tissues. EID3 knocking down significantly hindered glioma cell proliferation and invasion, as well as induced reduction of cell viability, apoptosis and cell death. EID3 knocking down also greatly inhibited tumor growth in SCID mice. Knocking down of AMPKα1 could effectively rescue glioma cells from apoptosis and cell death caused by EID3 absence, indicating that AMPKα1 acted as a key downstream regulator of EID3 and mediated suppression effects caused by EID3 knocking down inhibition. These findings were confirmed in glioma cells generated patient-derived xenograft models. AMPKα1 protein levels were affected by MG132 treatment in glioma, which suggested EID3 might down regulate AMPKα1 through protein degradation. CONCLUSION: Collectively, our study demonstrated that EID3 promoted glioma cell proliferation and survival by inhibiting AMPKα1 expression. Targeting EID3 might represent a promising strategy for treating glioma.

Molecular feature of neutrophils in immune microenvironment of muscle atrophy.

Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as ageing, disuse and denervation, tip the balance and induce skeletal muscle atrophy. Skeletal muscle atrophy, which involves complex physiological and biochemical changes, is accompanied by adverse outcomes and even increased mortality. Multiple studies have investigated the role of neutrophils in atrophied skeletal muscles; however, neutrophil intrusion in muscle is still a polemical knot. As technical obstacles have been overcome, people have gradually discovered new functions of neutrophils. The classical view of neutrophils is no longer applicable to their biological characteristics. To date, no clear association between the hidden injurious effect of neutrophil intrusion and muscle atrophy has been convincingly proven. Throughout this review, we have discussed the neutrophil activities that mediate muscle atrophy for distinct disease occurrences. Hopefully, this review will help both clinicians and researchers of skeletal muscle atrophy with relevant targets to further explore efficient medical interventions and treatments.

ROS-activated CXCR2+ neutrophils recruited by CXCL1 delay denervated skeletal muscle atrophy and undergo P53-mediated apoptosis.

Neutrophils are the earliest master inflammatory regulator cells recruited to target tissues after direct infection or injury. Although inflammatory factors are present in muscle that has been indirectly disturbed by peripheral nerve injury, whether neutrophils are present and play a role in the associated inflammatory process remains unclear. Here, intravital imaging analysis using spinning-disk confocal intravital microscopy was employed to dynamically identify neutrophils in denervated muscle. Slice digital scanning and 3D-view reconstruction analyses demonstrated that neutrophils escape from vessels and migrate into denervated muscle tissue. Analyses using reactive oxygen species (ROS) inhibitors and flow cytometry demonstrated that enhanced ROS activate neutrophils after denervation. Transcriptome analysis revealed that the vast majority of neutrophils in denervated muscle were of the CXCR2 subtype and were recruited by CXCL1. Most of these cells gradually disappeared within 1 week via P53-mediated apoptosis. Experiments using specific blockers confirmed that neutrophils slow the process of denervated muscle atrophy. Collectively, these results indicate that activated neutrophils are recruited via chemotaxis to muscle tissue that has been indirectly damaged by denervation, where they function in delaying atrophy.

Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin-p53 interaction.

BACKGROUND: Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a state of cell growth arrest owing to such stimuli as oxidation, can be caused by progerin. However, evidence for whether SIPS-induced progerin accumulation is connected to denervation-induced muscle atrophy is not sufficient. METHODS: Flow cytometry and a reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) inhibitors were used to assess the effect of oxidation on protein (p53), progerin, and nuclear progerin-p53 interaction in the denervated muscles of models of mice suffering from sciatic injury. Loss-of-function approach with the targeted deletion of p53 was used to assess connection among SIPS, denervated muscle atrophy, and fibrogenesis. RESULTS: The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. The abnormal accumulation of progerin in the nuclear membrane as well as the activation of nuclear progerin-p53 interaction triggered premature senescence in the denervated muscle cells of mice. The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis. CONCLUSION: Oxidative stress-triggered premature senescence via nuclear progerin-p53 interaction that promotes denervated skeletal muscular atrophy and fibrogenesis.

Research progress in immune microenvironment regulation of muscle atrophy induced by peripheral nerve injury.

Denervated skeletal muscular atrophy is primarily characterized by loss of muscle strength and mass and an unideal functional recovery of the muscle after extended denervation. This review emphasizes the interaction between the immune system and the denervated skeletal muscle. Immune cells such as neutrophils, macrophages and T-cells are activated and migrate to denervated muscle, where they release a high concentration of cytokines and chemokines. The migration of these immune cells, the transformation of different functional immune cell subtypes, and the cytokine network in the immune microenvironment may be involved in the regulatory process of muscle atrophy or repair. However, the exact mechanisms of the interaction between these immune cells and immune molecules in skeletal muscles are unclear. In this paper, the immune microenvironment regulation of muscle atrophy induced by peripheral nerve injury is reviewed.

Ficus carica L. Attenuates Denervated Skeletal Muscle Atrophy via PPARα/NF-κB Pathway.

Treatment options for denervated skeletal muscle atrophy are limited, in part because the underlying molecular mechanisms are not well understood. Unlike previous transcriptomics studies conducted in rodent models of peripheral nerve injury, in the present study, we performed high-throughput sequencing with denervated atrophic biceps muscle and normal (non-denervated) sternocleidomastoid muscle samples obtained from four brachial plexus injury (BPI) patients. We also investigated whether Ficus carica L. (FCL.) extract can suppress denervated muscle atrophy in a mouse model, along with the mechanism of action. We identified 1471 genes that were differentially expressed between clinical specimens of atrophic and normal muscle, including 771 that were downregulated and 700 that were upregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed genes were mainly enriched in the GO terms "structural constituent of muscle," "Z disc," "M band," and "striated muscle contraction," as well as "Cell adhesion molecules," "Glycolysis/Gluconeogenesis," "Peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway," and "P53 signaling pathway." In experiments using mice, the reduction in wet weight and myofiber diameter in denervated muscle was improved by FCL. extract compared to saline administration, which was accompanied by downregulation of the proinflammatory cytokines interleukin (IL)-1ß and IL-6. Moreover, although both denervated groups showed increased nuclear factor (NF)-κB activation and PPARα expression, the degree of NF-κB activation was lower while PPARα and inhibitor of NF-κB IκBα expression was higher in FCL. extract-treated mice. Thus, FCL. extract suppresses denervation-induced inflammation and attenuates muscle atrophy by enhancing PPARα expression and inhibiting NF-κB activation. These findings suggest that FCL. extract has therapeutic potential for preventing denervation-induced muscle atrophy caused by peripheral nerve injury or disease.

Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism.

Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes) 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-α and interleukin-6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor-α and interleukin-6 expression.