Analgesic Effect of Oliceridine Combined with Thoracic Paravertebral Nerve Block in Elderly Patients Undergoing Lung Cancer Resection and Its Impact on Neuroinflammation and Cognitive Function

Analgesic Effect of Oliceridine Combined with Thoracic Paravertebral Nerve Block in Elderly Patients Undergoing Lung Cancer Resection and Its Impact on Neuroinflammation and Cognitive Function | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Analgesic Effect of Oliceridine Combined with Thoracic Paravertebral Nerve Block in Elderly Patients Undergoing Lung Cancer Resection and Its Impact on Neuroinflammation and Cognitive Function Li Yang, Jin Zhang, Beiping Li, Ningning Ji This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8500085/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract [ Objective ]: To investigate the analgesic effect of Oliceridine combined with thoracic paravertebral block (TPVB) in radical surgery for lung cancer in elderly patients and its impact on neuroinflammation and postoperative cognitive function, aiming to provide new therapeutic strategies for postoperative pain management and cognitive function protection in elderly lung cancer patients. [ Methods ]: Eighty elderly patients who underwent thoracotomy for radical lung cancer surgery at Xuzhou First People's Hospital between October 2024 and August 2025 were selected and randomly divided into a control group and an experimental group, with 40 patients in each group. The control group received TPVB combined with conventional intravenous patient-controlled analgesia, while the experimental group received Oliceridine in addition to TPVB for intravenous patient-controlled analgesia. Postoperative pain was assessed using the Visual Analog Scale (VAS), and the levels of inflammatory mediators such as matrix metalloproteinase-9 (MMP-9), lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α) in plasma were measured at different time points postoperatively. Cognitive function was evaluated using the Montreal Cognitive Assessment (Moca), and the occurrence of adverse reactions was recorded in both groups. The VAS scores of the experimental group at 6 hours, 12 hours, 24 hours, and 48 hours postoperatively were significantly lower than those of the control group (P<0.05), indicating that the combined regimen has a good analgesic effect. At all postoperative time points, the plasma levels of MMP-9, Lp-PLA2, IL-6, and TNF-α in the experimental group were significantly lower than those in the control group (P<0.05), indicating that this regimen can effectively inhibit postoperative neuroinflammatory responses. On the 7th day post-surgery, the Moca score of the experimental group was significantly higher than that of the control group (P<0.05), suggesting that this combined regimen has a protective effect on postoperative cognitive function. Additionally, the incidence of adverse reactions in the experimental group was significantly lower than that in the control group (P<0.05). [ Conclusion ]: Oliceridine combined with TPVB demonstrates significant analgesic efficacy in radical surgery for elderly lung cancer patients, effectively inhibits postoperative neuroinflammatory responses, provides protective effects on postoperative cognitive function, and exhibits good safety, indicating its clinical value for promotion. Oliceridine Thoracic Paravertebral Block Analgesia Neuroinflammation Postoperative Cognitive Dysfunction Introduction As one of the most prevalent malignancies globally, the primary treatment for early-stage lung cancer primarily relies on radical surgery[1]. Postoperative pain is a widespread clinical issue that significantly impacts patient recovery outcomes; it may also lead to persistent pain, increase the risk of analgesic dependence, and exacerbate economic burdens[2]. Therefore, enhancing postoperative pain management protocols holds considerable clinical value. In the realm of analgesia for radical lung cancer surgery, despite the availability of various treatment options, the use of traditional opioids is limited due to their significant side effects[3-5]. In this context, multimodal analgesia strategies have gradually evolved, among which thoracic paravertebral block (TPVB), a regional anesthesia technique, has been shown to significantly enhance postoperative analgesia while modulating perioperative stress and inflammatory levels[6-8]. Notably, the novel G protein-biased μ-opioid receptor agonist oliceridine (OLI), approved in 2023, demonstrates favorable safety characteristics owing to its rapid onset, short half-life, and lower incidence of adverse reactions[9-10]. However, research on the combined application of TPVB and OLI for postoperative pain control, neuroinflammatory responses, and cognitive function remains relatively limited. Moreover, in the elderly patient population, postoperative cognitive dysfunction (POCD) is a common surgical complication that may involve mechanisms related to microglial activation induced by surgical trauma. This process promotes the release of inflammatory factors, disrupts the integrity of the blood-brain barrier, and ultimately leads to neuronal damage[11]. The prevention of postoperative cognitive dysfunction (POCD) has become a significant objective in clinical treatment [12]. This study represents the first attempt to integrate thoracic paravertebral block (TPVB) with the novel analgesic OLI in elderly patients undergoing radical lung cancer surgery. It emphasizes the comprehensive effects of this combined regimen on postoperative analgesia, neuroinflammatory responses, and cognitive function. This innovative treatment approach not only offers a superior option for postoperative pain management but also has the potential to prevent the onset of POCD by inhibiting neuroinflammatory responses, thereby paving the way for new therapeutic avenues in the postoperative recovery of elderly lung cancer patients. Research Methods and Subjects 1. Clinical Data: This study involved 160 elderly patients who underwent thoracotomy for radical lung cancer surgery at Xuzhou First People's Hospital between October 2024 and August 2025. The inclusion criteria were as follows: ASA classification of II-III, age between 65 and 80 years, and signed informed consent from the patients or their legal representatives. The exclusion criteria included: cardiac function classified as grade III or higher, severe malnutrition, abnormal preoperative liver and kidney function, psychiatric disorders or significant systemic diseases, recent usage of sedatives or psychotropic medications, a Montreal Cognitive Assessment (Moca) score below 24, auditory, visual, or language dysfunction, and a history of alcohol abuse or drug dependence. This study was conducted in accordance with the Declaration of Helsinki and received approval from the Ethics Committee of Xuzhou First People's Hospital (Approval No.: XYY11[2024]029). The ChiCTR registration number is ChiCTR2400090498（Registration date: 2024-10-06）. Informed consent procedures were completed by all participants and their family members. 2. Determination of Sample Size：In determining the sample size for this study, a comprehensive evaluation was conducted regarding the differences in postoperative pain assessment, specifically the Visual Analog Scale (VAS) score, as well as the incidence of Postoperative Cognitive Dysfunction (POCD). Based on prior research data, the anticipated mean difference in postoperative pain scores between the two groups was calculated to be 1.5 points, with a standard deviation of 1.2 points. Furthermore, considering the differences in POCD incidence reported in the relevant literature, the significance level (α) was established at 0.05, and the test power (1-β) was set at 0.80. Utilizing the appropriate sample size estimation method, it was initially determined that a minimum of 16 patients would be necessary per group. However, accounting for potential sample attrition, the final decision was made to include 40 patients in each group.Grouping Scheme: Subjects were equally allocated to the control group and the experimental group using a random number table method. The control group received TPVB combined with conventional intravenous patient-controlled analgesia, while the experimental group received OLI in addition to TPVB for intravenous patient-controlled analgesia. The study employed a double-blind design, and the required sample size was calculated by R software based on effect size, statistical power, and significance level. 3. Anesthesia Protocol:During the procedure, the patient was continuously monitored for invasive blood pressure (BP), oxygen saturation (SpO2), electrocardiogram (ECG), and Narcotrend anesthesia depth. Right internal jugular vein catheterization was performed under local anesthesia. All study subjects received general anesthesia via double-lumen endotracheal intubation. Arterial blood pressure was continuously monitored through radial artery catheterization. The thoracic paravertebral block (TPVB) was precisely located using the Venue50 ultrasound system, with the block performed at the T4 level. Following the expulsion of blood and gas, 0.375% ropivacaine (2 mg/kg) was injected, followed by a 10-minute observation period to assess the block level. The anesthesia induction protocol was administered in the following sequence: intravenous injection of midazolam (0.05-0.1 mg/kg), etomidate (0.3 mg/kg), sufentanil (0.4 μg/kg), and rocuronium (0.6 mg/kg). During the operation, volume-controlled ventilation was employed with parameters set to a tidal volume of 6-8 ml/kg, a respiratory rate of 15 breaths per minute, and an inspiration-to-expiration ratio of 1:2, maintaining a PETCO2 of 30-35 mmHg. The Narcotrend index was maintained within the D2-E1 range, and body temperature was kept at 36-37°C. Postoperatively, the control group received a conventional patient-controlled intravenous analgesia regimen, while the study group was administered Oliceridine Fumarate Injection (OLI) (Jiangsu Nhwa Pharmaceutical Co., Ltd., National Medicine Approval No. H20233511, specification 30 mL: 30 mg) for analgesia, with an initial dose of 1.5 mg, followed by patient-controlled intravenous analgesia at 5 μg/kg after 10 minutes, a continuous infusion rate of 0.35 mg/h, and a lockout interval of 6 minutes. Both groups maintained analgesia for 48 hours postoperatively. 4. Primary Outcome Measure:The primary outcome measure of this study is the analgesic effect. The Visual Analog Scale (VAS) was utilized as the main assessment tool. This scoring system employs a 0-10 point scale, where 0 denotes no pain and 10 signifies severe pain, with higher scores indicating greater pain intensity. Assessment time points were established at 6 hours (T1), 12 hours (T2), 24 hours (T3), and 48 hours (T4) postoperatively, with a designated physician conducting standardized evaluations for both patient groups. 5. Secondary Endpoints:The secondary evaluation criteria of this study encompass two key aspects: 1) **Inflammatory Indicators**: Venous blood samples were collected at five time points: 24 hours preoperatively (T0), and 6 hours (T1), 12 hours (T2), 24 hours (T3), and 48 hours (T4) postoperatively. The concentrations of plasma matrix metalloproteinase-9 (MMP-9), lipoprotein-phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were quantified using enzyme-linked immunosorbent assay (ELISA) methodology. The MMP-9 and Lp-PLA2 detection kits were supplied by Jiangsu Enzyme Immunoassay Industrial Co., Ltd., while the IL-6 and TNF-α detection kits were procured from eBioscience, USA. All procedures were meticulously executed in accordance with the kit instructions. 2) **Postoperative Adverse Reactions**: Adverse reactions such as nausea, vomiting, drowsiness, and respiratory depression occurring postoperatively were recorded and statistically analyzed, with the incidence of these adverse reactions used to assess postoperative safety. 3) **Cognitive Function Assessment**: Cognitive function was evaluated using the Montreal Cognitive Assessment (Moca) scale one day prior to surgery and seven days postoperatively (or on the day of discharge if the patient was discharged earlier than the seventh day). This assessment included 12 items covering orientation, memory, attention and calculation ability, recall ability, and language ability [13]. The evaluation was conducted independently by two associate chief physicians. 6. Statistical analysis: Data processing was performed using SPSS version 26.0. Continuous variables were expressed as mean ± standard deviation (M ± SD), while categorical variables were presented as frequencies or percentages. For time-series data within the same group, repeated measures analysis of variance was utilized for assessment. Comparisons between different groups were conducted using one-way analysis of variance, and the significance of differences in categorical data was determined using the chi-square test. The statistical significance level was set at α = 0.05, with results considered statistically significant when the P-value fell below this threshold. Results 1. Analysis of the basic information of the two groups: statistical analysis of the basic information of the two groups indicated no statistically significant differences in gender composition, age distribution, body mass index, operation duration, preoperative Moca scores, intraoperative blood loss, American Society of Anesthesiologists (ASA) classification, education level, and medical history, including hypertension, diabetes, and coronary heart disease (P > 0.05). Detailed data can be found in Table 1. Additionally, in the plasma samples collected 24 hours prior to the operation, the concentrations of MMP-9, Lp-PLA2, IL-6, and TNF-α also did not show significant differences (P > 0.05). These findings strongly support the comparability of the baseline characteristics of the study subjects, as further detailed in Table 1. Table 1 Comparison of Preoperative General Conditions Between the Two Groups of Patients. Index Control Group (n=80) Experimental group(n=80) F/ χ² P Gender /(Male/Female) 46/34 45/35 0.025 0.873 Age / (Years) 71.39±4.96 70.85±5.34 1.983 0.80 BMI/（kg/m²） 27.41±2.31 26.85±2.52 1.981 0.212 Operation time/(min) 136.95±26.31 137.82±27.45 0.205 0.838 Intraoperative blood loss（ml） 244.89±45.56 238.47±39.76 1.981 0.416 ASA classification(Ⅱ/Ⅲ) 23/34 25/36 0.005 0.944 Hypertension case 31 30 0.320 0.802 Diabetes/case 16 14 0.407 0.523 Coronary heart disease/case 8 11 0.349 0.555 2. Analysis of Postoperative Pain Assessment Results: The VAS was used to measure patients in both groups. The results showed that during the postoperative observation period (T1-T4), the pain scores in the experimental group were significantly lower than those in the control group (P<0.05). Specific data are detailed in Table 2. Table 2 Comparison of VAS Scores at Different Time Points Between the Two Groups (x±s, points) Group . n T1 T2 T3 T4 Control Group 80 6.84±1.11 5.79±1.10 3.49±0.68 1.75±0.40 Experimental group 80 5.31±1.08* 4.42±1.03* 2.79±0.28* 1.39±0.34* *Compared with the control group, the differences at each time point were statistically significant (P<0.05). 3. Dynamic Monitoring of Inflammatory Levels:At 24 hours preoperatively (T0), no significant differences were observed in plasma levels of MMP-9, Lp-PLA2, IL-6, and TNF-α between the two groups (all P-values > 0.05). In comparison to T0, plasma levels of MMP-9, Lp-PLA2, IL-6, and TNF-α in both groups exhibited significant increases at various postoperative time points (all P-values < 0.05). Throughout the monitoring period from T1 to T4 postoperatively, the aforementioned inflammatory indicators were significantly lower in the experimental group compared to the control group, with all differences reaching statistical significance (all P < 0.01).Specific data are detailed in Table 3. Table 3 Plasma concentrations of MMP-9, Lp-PLA2, IL-6, and TNF-α in two groups Index Time point Control Group Experimental group t/ χ² P MMP-9 (μg/L) T0 472.34±84.37 473.81±85.74 0.109 0.913 T1 871.80±106.31* 801.58±104.65*# 4.210 0.000 T2 933.43±104.56* 885.71±107.89*# 2.841 0.005 T3 975.67±101.21* 878.48±99.62*# 6.121 0.000 T4 833.64±116.43* 783.76±112.51*# 2.756 0.007 Lp-PLA2 (μg/L) T0 27.53±4.87 26.59±4.67 1.23 0.223 T1 51.34±10.71* 44.13±9.41*# 4.523 0.000 T2 56.72±9.58* 43.77±8.93*# 8.844 0.000 T3 62.41±11.72* 57.64±10.56*# 2.704 0.008 T4 61.75±10.32* 54.34±9.79*# 4.659 0.000 IL-6 (pg/mL) T0 4.41±0.79 4.47±0.80 0.06 0.954 T1 9.92±1.69* 7.89±1.63*# 3.77 0.001 T2 9.72±1.49* 8.73±1.16*# 4.689 0.000 T3 8.99±1.01* 7.82±0.91*# 7.689 0.000 T4 9.01±1.57* 8.25±1.12*# 2.49 0.017 TNF-α (pg/mL) T0 1.33±0.55 1.28±0.46 0.14 0.890 T1 4.37±0.55* 3.25±0.60*# 12.308 0.000 T2 4.41±0.55* 3.61±0.61*# 8.712 0.000 T3 4.39±0.45* 3.91±0.35*# 7.531 0.000 T4 4.38±0.82* 3.85±0.59*# 4.693 0.000 Note: *Compared with T0, the difference was statistically significant (P<0.05);. #compared to the control group,the difference was statistically significant (P 0.05). On the seventh day post-surgery, the Moca scores in the control group were significantly lower than their preoperative scores (P > 0.05). In contrast, the experimental group exhibited significantly higher Moca scores on the seventh day post-surgery compared to the control group (P < 0.0001).Specific data are detailed in Table 4. Table 4 Changes in Moca Scores Pre- and Post-Surgery in Both Groups. Time point Control Group Experimental group t P 1 day before surgery 25.48±2.32 25.02±2.38 1.265 0.208 7 days post-operation 22.06±2.24* 24.01±2.08# 0.279 0.000 *Compared with 1 day before surgery, the difference was statistically significant (P<0.05); # Compared with the control group, the difference was statistically significant (P<0.05) 5. Comparison of Adverse Reactions: In the control group, a total of 18 cases of nausea and vomiting, 3 cases of respiratory depression, and 10 cases of dizziness were observed, resulting in an overall adverse reaction rate of 38.75%. In contrast, the experimental group recorded only 12 cases of nausea and vomiting, 6 cases of dizziness, and 1 case of respiratory depression, which reduced the adverse reaction rate to 23.75%. Analysis using the χ² test (χ²=4.189, P=0.041) indicated that the adverse reaction rate in the experimental group was significantly lower than that in the control group, with the difference being statistically significant. Specific data are detailed in Table 5. Table 5 Comparison of Adverse Reactions Between the Two Groups. Group/Adverse Reaction Respiratory depression Dizziness Nausea and vomiting Total Control Group （n=80） 3 10 18 31 Experimental group （n=80） 1 6 12 19* Note: *Compared with the control group, P<0.05. Discussion Elderly patients undergoing radical surgery for lung cancer often encounter significant challenges in pain management, particularly in relation to concurrent postoperative cognitive dysfunction (POCD). While traditional opioid analgesics are effective in providing analgesia, their administration in high doses is associated with a range of side effects, including respiratory depression, dizziness, drowsiness, and nausea and vomiting, which may limit their clinical applicability. In contrast, Oliceridine (OLI), a G protein-biased μ-opioid receptor agonist, offers notable safety advantages due to its rapid onset, short half-life, and a lower incidence of respiratory depression and gastrointestinal side effects. Thoracic paravertebral block (TPVB), a regional anesthesia technique, effectively obstructs nerve conduction on the surgical side by delivering anesthetic agents through the thoracic paravertebral space, thereby reducing intraoperative nerve injury. Research indicates that this nerve block not only alleviates postoperative pain but also indirectly protects cognitive function by mitigating pain-related inflammatory responses, while concurrently decreasing the reliance on systemic opioids and their associated adverse effects. Our study demonstrated that the treatment regimen combining TPVB with OLI resulted in significantly lower Visual Analog Scale (VAS) scores at 6, 12, 24, and 48 hours postoperatively compared to the control group, thereby confirming the sustained analgesic effect of this regimen within 48 hours following surgery. Furthermore, the incidence of adverse reactions in the experimental group was significantly lower than that in the control group, suggesting that this combined approach effectively enhances postoperative comfort and minimizes the risk of adverse reactions while maintaining analgesic efficacy. Postoperative cognitive dysfunction (POCD) is a prevalent complication among elderly surgical patients, with its pathogenesis closely linked to neuroinflammatory responses [18]. Surgical stimulation can activate microglia, resulting in the excessive release of various inflammatory mediators, including matrix metalloproteinase-9 (MMP-9), lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). These bioactive substances may exert neurotoxic effects by inducing blood-brain barrier dysfunction and promoting the aggregation of pro-inflammatory factors, ultimately leading to cognitive decline [19]. Research data indicate that, compared to the control group, the experimental group receiving thoracic paravertebral block (TPVB) combined with opioid-lidocaine infusion (OLI) exhibited a significant reduction in the aforementioned inflammatory markers at various postoperative time points, demonstrating that this combined regimen effectively inhibits surgery-induced neuroinflammatory responses. To ensure the accuracy of cognitive function assessments, the research team conducted cognitive function tests 24 hours preoperatively and on the 7th postoperative day, by which time the anesthetic drugs had largely been metabolized, thereby minimizing the interference of drug residues on the evaluation results. On the 7th postoperative day, the Montreal Cognitive Assessment (Moca) scores of the experimental group showed a statistically significant improvement compared to the control group, validating the unique advantages of the combined TPVB and OLI strategy in inhibiting neuroinflammation and preserving cognitive function. From the perspective of the mechanism of action, the neuroprotective effects of the TPVB-OLI combination therapy may arise from several pathways. Firstly, TPVB selectively blocks nerve conduction in the surgical area, effectively minimizing the risk of mechanical damage to neural tissues during the operation. Secondly, TPVB may significantly inhibit the production and release of inflammatory mediators by modulating key upstream signaling pathways involved in neuroinflammatory responses. Lastly, as a novel opioid, OLI not only exhibits a rapid onset and a short metabolic half-life but also enhances the safety of clinical application due to its lower incidence of respiratory depression and gastrointestinal adverse reactions. The synergistic effects of these two treatment modalities may operate through multiple mechanisms, significantly alleviating postoperative pain symptoms and thereby reducing the negative impact of pain-related stress responses on cognitive functions. This study confirms that, compared to TPVB combined with conventional patient-controlled intravenous analgesia, the combination of TPVB and OLI demonstrates superior analgesic efficacy in elderly patients undergoing radical lung cancer surgery. Furthermore, it effectively suppresses postoperative neuroinflammation and positively impacts cognitive function. The incidence of adverse reactions associated with this combined regimen is low, and its safety profile is favorable, indicating its potential as a preferred option for postoperative pain management and its clinical promotion value. However, limitations such as a small sample size and short follow-up duration necessitate subsequent research to conduct larger-scale, multicenter, long-term follow-up clinical trials to validate these findings and explore its application prospects in other surgical fields. Additionally, a deeper understanding of the mechanisms by which this regimen alleviates neuroinflammation and protects cognitive function will provide a more robust theoretical basis for clinical practice. Declarations Ethics Approval and Consent to Participate This study was approved by the Ethics Committee of Xuzhou First People's Hospital (Approval No: XYY11[2024]029) and registered as a clinical trial with the registration number ChiCTR2400090498. All participants provided written informed consent before any study-related procedures. Funding This study was supported by the following grants: - Xuzhou Municipal Medical and Health General Project (2023) (KC23160) - Xuzhou Medical University Affiliated Hospital Development Fund Project (XYFM202236) Competing Interests The authors declare no competing interests. Author Contribution Y.L. (Yang Li): conception and design of the study, acquisition of funding, drafting the manuscript, final approval.J.N.N. (Ji Ningning): patient recruitment, randomization, peri-operative data collection, critical revision of the manuscript.Z.J. (Zhang Jin): ultrasound-guided TPVB performance, anesthesia management, statistical analysis, preparation of tables and figures.L.B.P. (Li Beiping): neuro-cognitive assessments, biomarker measurements, interpretation of inflammatory data, revision of the discussion. 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The neuroprotective effects of spray-dried porcine plasma supplementation involve the microbiota-gut-brain axis[J].Nutrients,2022,14(11):2211. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 19 Jan, 2026 Reviewers agreed at journal 18 Jan, 2026 Reviewers invited by journal 13 Jan, 2026 Editor assigned by journal 04 Jan, 2026 Submission checks completed at journal 04 Jan, 2026 First submitted to journal 02 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8500085","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":573727266,"identity":"22e07da8-6b48-4f91-8033-637c1474a1b6","order_by":0,"name":"Li Yang","email":"","orcid":"","institution":"The First People's Hospital of Xuzhou","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Yang","suffix":""},{"id":573727267,"identity":"46c7da06-6eed-49ad-a014-45de251bd9cd","order_by":1,"name":"Jin Zhang","email":"","orcid":"","institution":"The First People's Hospital of 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Hospital of Xuzhou","correspondingAuthor":true,"prefix":"","firstName":"Ningning","middleName":"","lastName":"Ji","suffix":""}],"badges":[],"createdAt":"2026-01-02 10:38:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8500085/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8500085/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100249201,"identity":"acaed97c-b3dd-4b80-9d1c-39abb8e280df","added_by":"auto","created_at":"2026-01-14 14:45:18","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":33963,"visible":true,"origin":"","legend":"","description":"","filename":"AnalgesicEffectofOliceridineCombinedwithThor.docx","url":"https://assets-eu.researchsquare.com/files/rs-8500085/v1/248eca1d16d31401ed8aa2cf.docx"},{"id":100249200,"identity":"85aec335-514d-48e2-b19f-88d22678dae1","added_by":"auto","created_at":"2026-01-14 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10:47:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":604503,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8500085/v1/8f5cd22b-f463-4ecf-80bb-53370e77762c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analgesic Effect of Oliceridine Combined with Thoracic Paravertebral Nerve Block in Elderly Patients Undergoing Lung Cancer Resection and Its Impact on Neuroinflammation and Cognitive Function","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAs one of the most prevalent malignancies globally, the primary treatment for early-stage lung cancer primarily relies on radical surgery[1]. Postoperative pain is a widespread clinical issue that significantly impacts patient recovery outcomes; it may also lead to persistent pain, increase the risk of analgesic dependence, and exacerbate economic burdens[2]. Therefore, enhancing postoperative pain management protocols holds considerable clinical value. In the realm of analgesia for radical lung cancer surgery, despite the availability of various treatment options, the use of traditional opioids is limited due to their significant side effects[3-5]. In this context, multimodal analgesia strategies have gradually evolved, among which thoracic paravertebral block (TPVB), a regional anesthesia technique, has been shown to significantly enhance postoperative analgesia while modulating perioperative stress and inflammatory levels[6-8]. Notably, the novel G protein-biased \u0026mu;-opioid receptor agonist oliceridine (OLI), approved in 2023, demonstrates favorable safety characteristics owing to its rapid onset, short half-life, and lower incidence of adverse reactions[9-10]. However, research on the combined application of TPVB and OLI for postoperative pain control, neuroinflammatory responses, and cognitive function remains relatively limited. Moreover, in the elderly patient population, postoperative cognitive dysfunction (POCD) is a common surgical complication that may involve mechanisms related to microglial activation induced by surgical trauma. This process promotes the release of inflammatory factors, disrupts the integrity of the blood-brain barrier, and ultimately leads to neuronal damage[11]. The prevention of postoperative cognitive dysfunction (POCD) has become a significant objective in clinical treatment [12]. This study represents the first attempt to integrate thoracic paravertebral block (TPVB) with the novel analgesic OLI in elderly patients undergoing radical lung cancer surgery. It emphasizes the comprehensive effects of this combined regimen on postoperative analgesia, neuroinflammatory responses, and cognitive function. This innovative treatment approach not only offers a superior option for postoperative pain management but also has the potential to prevent the onset of POCD by inhibiting neuroinflammatory responses, thereby paving the way for new therapeutic avenues in the postoperative recovery of elderly lung cancer patients.\u003c/p\u003e"},{"header":"Research Methods and Subjects","content":"\u003cp\u003e1.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Clinical Data: This study involved 160 elderly patients who underwent thoracotomy for radical lung cancer surgery at Xuzhou First People\u0026apos;s Hospital between October 2024 and August 2025. The inclusion criteria were as follows: ASA classification of II-III, age between 65 and 80 years, and signed informed consent from the patients or their legal representatives. The exclusion criteria included: cardiac function classified as grade III or higher, severe malnutrition, abnormal preoperative liver and kidney function, psychiatric disorders or significant systemic diseases, recent usage of sedatives or psychotropic medications, a Montreal Cognitive Assessment (Moca) score below 24, auditory, visual, or language dysfunction, and a history of alcohol abuse or drug dependence. This study was conducted in accordance with the Declaration of Helsinki and received approval from the Ethics Committee of Xuzhou First People\u0026apos;s Hospital (Approval No.: XYY11[2024]029). The ChiCTR registration number is ChiCTR2400090498（Registration date: 2024-10-06）. Informed consent procedures were completed by all participants and their family members.\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Determination of Sample Size：In determining the sample size for this study, a comprehensive evaluation was conducted regarding the differences in postoperative pain assessment, specifically the Visual Analog Scale (VAS) score, as well as the incidence of Postoperative Cognitive Dysfunction (POCD). Based on prior research data, the anticipated mean difference in postoperative pain scores between the two groups was calculated to be 1.5 points, with a standard deviation of 1.2 points. Furthermore, considering the differences in POCD incidence reported in the relevant literature, the significance level (\u0026alpha;) was established at 0.05, and the test power (1-\u0026beta;) was set at 0.80. Utilizing the appropriate sample size estimation method, it was initially determined that a minimum of 16 patients would be necessary per group. However, accounting for potential sample attrition, the final decision was made to include 40 patients in each group.Grouping Scheme: Subjects were equally allocated to the control group and the experimental group using a random number table method. \u0026nbsp;The control group received TPVB combined with conventional intravenous patient-controlled analgesia, while the experimental group received OLI in addition to TPVB for intravenous patient-controlled analgesia. \u0026nbsp;The study employed a double-blind design, and the required sample size was calculated by R software based on effect size, statistical power, and significance level.\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Anesthesia Protocol:During the procedure, the patient was continuously monitored for invasive blood pressure (BP), oxygen saturation (SpO2), electrocardiogram (ECG), and Narcotrend anesthesia depth. Right internal jugular vein catheterization was performed under local anesthesia. All study subjects received general anesthesia via double-lumen endotracheal intubation. Arterial blood pressure was continuously monitored through radial artery catheterization. The thoracic paravertebral block (TPVB) was precisely located using the Venue50 ultrasound system, with the block performed at the T4 level. Following the expulsion of blood and gas, 0.375% ropivacaine (2 mg/kg) was injected, followed by a 10-minute observation period to assess the block level. The anesthesia induction protocol was administered in the following sequence: intravenous injection of midazolam (0.05-0.1 mg/kg), etomidate (0.3 mg/kg), sufentanil (0.4 \u0026mu;g/kg), and rocuronium (0.6 mg/kg). During the operation, volume-controlled ventilation was employed with parameters set to a tidal volume of 6-8 ml/kg, a respiratory rate of 15 breaths per minute, and an inspiration-to-expiration ratio of 1:2, maintaining a PETCO2 of 30-35 mmHg. The Narcotrend index was maintained within the D2-E1 range, and body temperature was kept at 36-37\u0026deg;C. Postoperatively, the control group received a conventional patient-controlled intravenous analgesia regimen, while the study group was administered Oliceridine Fumarate Injection (OLI) (Jiangsu Nhwa Pharmaceutical Co., Ltd., National Medicine Approval No. H20233511, specification 30 mL: 30 mg) for analgesia, with an initial dose of 1.5 mg, followed by patient-controlled intravenous analgesia at 5 \u0026mu;g/kg after 10 minutes, a continuous infusion rate of 0.35 mg/h, and a lockout interval of 6 minutes. Both groups maintained analgesia for 48 hours postoperatively.\u003c/p\u003e\n\u003cp\u003e4.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Primary Outcome Measure:The primary outcome measure of this study is the analgesic effect. The Visual Analog Scale (VAS) was utilized as the main assessment tool. This scoring system employs a 0-10 point scale, where 0 denotes no pain and 10 signifies severe pain, with higher scores indicating greater pain intensity. Assessment time points were established at 6 hours (T1), 12 hours (T2), 24 hours (T3), and 48 hours (T4) postoperatively, with a designated physician conducting standardized evaluations for both patient groups.\u003c/p\u003e\n\u003cp\u003e5.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Secondary Endpoints:The secondary evaluation criteria of this study encompass two key aspects: 1) **Inflammatory Indicators**: Venous blood samples were collected at five time points: 24 hours preoperatively (T0), and 6 hours (T1), 12 hours (T2), 24 hours (T3), and 48 hours (T4) postoperatively. The concentrations of plasma matrix metalloproteinase-9 (MMP-9), lipoprotein-phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), and tumor necrosis factor-\u0026alpha; (TNF-\u0026alpha;) were quantified using enzyme-linked immunosorbent assay (ELISA) methodology. The MMP-9 and Lp-PLA2 detection kits were supplied by Jiangsu Enzyme Immunoassay Industrial Co., Ltd., while the IL-6 and TNF-\u0026alpha; detection kits were procured from eBioscience, USA. All procedures were meticulously executed in accordance with the kit instructions. 2) **Postoperative Adverse Reactions**: Adverse reactions such as nausea, vomiting, drowsiness, and respiratory depression occurring postoperatively were recorded and statistically analyzed, with the incidence of these adverse reactions used to assess postoperative safety. 3) **Cognitive Function Assessment**: Cognitive function was evaluated using the Montreal Cognitive Assessment (Moca) scale one day prior to surgery and seven days postoperatively (or on the day of discharge if the patient was discharged earlier than the seventh day). This assessment included 12 items covering orientation, memory, attention and calculation ability, recall ability, and language ability [13]. The evaluation was conducted independently by two associate chief physicians.\u003c/p\u003e\n\u003cp\u003e6. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Statistical analysis: Data processing was performed using SPSS version 26.0. Continuous variables were expressed as mean \u0026plusmn; standard deviation (M \u0026plusmn; SD), while categorical variables were presented as frequencies or percentages. For time-series data within the same group, repeated measures analysis of variance was utilized for assessment. Comparisons between different groups were conducted using one-way analysis of variance, and the significance of differences in categorical data was determined using the chi-square test. The statistical significance level was set at \u0026alpha; = 0.05, with results considered statistically significant when the P-value fell below this threshold.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e1.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Analysis of the basic information of the two groups: statistical analysis of the basic information of the two groups indicated no statistically significant differences in gender composition, age distribution, body mass index, operation duration, preoperative Moca scores, intraoperative blood loss, American Society of Anesthesiologists (ASA) classification, education level, and medical history, including hypertension, diabetes, and coronary heart disease (P \u0026gt; 0.05). Detailed data can be found in Table 1. Additionally, in the plasma samples collected 24 hours prior to the operation, the concentrations of MMP-9, Lp-PLA2, IL-6, and TNF-\u0026alpha; also did not show significant differences (P \u0026gt; 0.05). These findings strongly support the comparability of the baseline characteristics of the study subjects, as further detailed in Table 1.\u003c/p\u003e\n\u003cp\u003eTable 1 Comparison of Preoperative General Conditions Between the Two Groups of Patients.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndex\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl Group (n=80)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental group(n=80)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/\u003c/strong\u003e\u003cstrong\u003e\u0026chi;\u0026sup2;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eGender /(Male/Female)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e46/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e45/35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.025\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.873\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eAge / (Years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e71.39\u0026plusmn;4.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e70.85\u0026plusmn;5.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e1.983\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eBMI/（kg/m\u0026sup2;）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e27.41\u0026plusmn;2.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e26.85\u0026plusmn;2.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e1.981\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eOperation time/(min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e136.95\u0026plusmn;26.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e137.82\u0026plusmn;27.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.838\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eIntraoperative blood loss（ml）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e244.89\u0026plusmn;45.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e238.47\u0026plusmn;39.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e1.981\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.416\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eASA classification(Ⅱ/Ⅲ)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e23/34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e25/36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.005\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.944\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eHypertension case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.320\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.802\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eDiabetes/case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.407\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.523\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 179px;\"\u003e\n \u003cp\u003eCoronary heart disease/case\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.349\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.555\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Analysis of Postoperative Pain Assessment Results: The VAS was used to measure patients in both groups. \u0026nbsp;The results showed that during the postoperative observation period (T1-T4), the pain scores in the experimental group were significantly lower than those in the control group (P\u0026lt;0.05). \u0026nbsp;Specific data are detailed in Table 2.\u003c/p\u003e\n\u003cp\u003eTable 2 Comparison of VAS Scores at Different Time Points Between the Two Groups (x\u0026plusmn;s, points)\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl Group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e6.84\u0026plusmn;1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e5.79\u0026plusmn;1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e3.49\u0026plusmn;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e1.75\u0026plusmn;0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e5.31\u0026plusmn;1.08*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e4.42\u0026plusmn;1.03*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e2.79\u0026plusmn;0.28*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e1.39\u0026plusmn;0.34*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*Compared with the control group, the differences at each time point were statistically significant (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e3.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Dynamic Monitoring of Inflammatory Levels:At 24 hours preoperatively (T0), no significant differences were observed in plasma levels of MMP-9, Lp-PLA2, IL-6, and TNF-\u0026alpha; between the two groups (all P-values \u0026gt; 0.05). In comparison to T0, plasma levels of MMP-9, Lp-PLA2, IL-6, and TNF-\u0026alpha; in both groups exhibited significant increases at various postoperative time points (all P-values \u0026lt; 0.05). Throughout the monitoring period from T1 to T4 postoperatively, the aforementioned inflammatory indicators were significantly lower in the experimental group compared to the control group, with all differences reaching statistical significance (all P \u0026lt; 0.01).Specific data are detailed in Table 3.\u003c/p\u003e\n\u003cp\u003eTable 3 Plasma concentrations of MMP-9, Lp-PLA2, IL-6, and TNF-\u0026alpha; in two groups\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime point\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl Group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et/\u003c/strong\u003e\u003cstrong\u003e\u0026chi;\u0026sup2;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 121px;\"\u003e\n \u003cp\u003eMMP-9 (\u0026mu;g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e472.34\u0026plusmn;84.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e473.81\u0026plusmn;85.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.913\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e871.80\u0026plusmn;106.31*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e801.58\u0026plusmn;104.65*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e4.210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e933.43\u0026plusmn;104.56*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e885.71\u0026plusmn;107.89*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e2.841\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e975.67\u0026plusmn;101.21*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e878.48\u0026plusmn;99.62*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e6.121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e833.64\u0026plusmn;116.43*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e783.76\u0026plusmn;112.51*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e2.756\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 121px;\"\u003e\n \u003cp\u003eLp-PLA2 (\u0026mu;g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e27.53\u0026plusmn;4.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e26.59\u0026plusmn;4.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e1.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.223\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e51.34\u0026plusmn;10.71*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e44.13\u0026plusmn;9.41*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e4.523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e56.72\u0026plusmn;9.58*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e43.77\u0026plusmn;8.93*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e8.844\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e62.41\u0026plusmn;11.72*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e57.64\u0026plusmn;10.56*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e2.704\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e61.75\u0026plusmn;10.32*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e54.34\u0026plusmn;9.79*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e4.659\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 121px;\"\u003e\n \u003cp\u003eIL-6 (pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e4.41\u0026plusmn;0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e4.47\u0026plusmn;0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.954\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e9.92\u0026plusmn;1.69*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e7.89\u0026plusmn;1.63*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e3.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e9.72\u0026plusmn;1.49*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e8.73\u0026plusmn;1.16*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e4.689\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e8.99\u0026plusmn;1.01*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e7.82\u0026plusmn;0.91*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e7.689\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e9.01\u0026plusmn;1.57*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e8.25\u0026plusmn;1.12*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e2.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 121px;\"\u003e\n \u003cp\u003eTNF-\u0026alpha; (pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e1.33\u0026plusmn;0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e1.28\u0026plusmn;0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.890\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e4.37\u0026plusmn;0.55*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e3.25\u0026plusmn;0.60*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e12.308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e4.41\u0026plusmn;0.55*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e3.61\u0026plusmn;0.61*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e8.712\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e4.39\u0026plusmn;0.45*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e3.91\u0026plusmn;0.35*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e7.531\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e4.38\u0026plusmn;0.82*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e3.85\u0026plusmn;0.59*#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e4.693\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNote: *Compared with T0, the difference was statistically significant (P\u0026lt;0.05);.\u003c/p\u003e\n\u003cp\u003e#compared to the control group,the difference was statistically significant (P\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e4.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Changes in Moca Scores:There was no statistically significant difference in Moca scores between the two patient groups one day prior to surgery (P \u0026gt; 0.05). On the seventh day post-surgery, the Moca scores in the control group were significantly lower than their preoperative scores (P \u0026gt; 0.05). In contrast, the experimental group exhibited significantly higher Moca scores on the seventh day post-surgery compared to the control group (P \u0026lt; 0.0001).Specific data are detailed in Table 4.\u003c/p\u003e\n\u003cp\u003eTable 4 Changes in Moca Scores Pre- and Post-Surgery in Both Groups.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime point\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl Group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e1 day before surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e25.48\u0026plusmn;2.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e25.02\u0026plusmn;2.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e1.265\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.208\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 186px;\"\u003e\n \u003cp\u003e7 days post-operation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 116px;\"\u003e\n \u003cp\u003e22.06\u0026plusmn;2.24*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e24.01\u0026plusmn;2.08#\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 62px;\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e*Compared with 1 day before surgery, the difference was statistically significant (P\u0026lt;0.05);\u003c/p\u003e\n\u003cp\u003e# Compared with the control group, the difference was statistically significant (P\u0026lt;0.05)\u003c/p\u003e\n\u003cp\u003e5.\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Comparison of Adverse Reactions: In the control group, a total of 18 cases of nausea and vomiting, 3 cases of respiratory depression, and 10 cases of dizziness were observed, resulting in an overall adverse reaction rate of 38.75%. In contrast, the experimental group recorded only 12 cases of nausea and vomiting, 6 cases of dizziness, and 1 case of respiratory depression, which reduced the adverse reaction rate to 23.75%. Analysis using the \u0026chi;\u0026sup2; test (\u0026chi;\u0026sup2;=4.189, P=0.041) indicated that the adverse reaction rate in the experimental group was significantly lower than that in the control group, with the difference being statistically significant. Specific data are detailed in Table 5.\u003c/p\u003e\n\u003cp\u003eTable 5 Comparison of Adverse Reactions Between the Two Groups.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"568\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup/Adverse Reaction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRespiratory depression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDizziness\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNausea and vomiting\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl Group\u003c/strong\u003e（n=80）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental group\u003c/strong\u003e（n=80）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 132px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e19*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNote: *Compared with the control group, P\u0026lt;0.05.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eElderly patients undergoing radical surgery for lung cancer often encounter significant challenges in pain management, particularly in relation to concurrent postoperative cognitive dysfunction (POCD). While traditional opioid analgesics are effective in providing analgesia, their administration in high doses is associated with a range of side effects, including respiratory depression, dizziness, drowsiness, and nausea and vomiting, which may limit their clinical applicability. In contrast, Oliceridine (OLI), a G protein-biased \u0026mu;-opioid receptor agonist, offers notable safety advantages due to its rapid onset, short half-life, and a lower incidence of respiratory depression and gastrointestinal side effects. Thoracic paravertebral block (TPVB), a regional anesthesia technique, effectively obstructs nerve conduction on the surgical side by delivering anesthetic agents through the thoracic paravertebral space, thereby reducing intraoperative nerve injury. Research indicates that this nerve block not only alleviates postoperative pain but also indirectly protects cognitive function by mitigating pain-related inflammatory responses, while concurrently decreasing the reliance on systemic opioids and their associated adverse effects. Our study demonstrated that the treatment regimen combining TPVB with OLI resulted in significantly lower Visual Analog Scale (VAS) scores at 6, 12, 24, and 48 hours postoperatively compared to the control group, thereby confirming the sustained analgesic effect of this regimen within 48 hours following surgery. Furthermore, the incidence of adverse reactions in the experimental group was significantly lower than that in the control group, suggesting that this combined approach effectively enhances postoperative comfort and minimizes the risk of adverse reactions while maintaining analgesic efficacy.\u003c/p\u003e\n\u003cp\u003ePostoperative cognitive dysfunction (POCD) is a prevalent complication among elderly surgical patients, with its pathogenesis closely linked to neuroinflammatory responses [18]. Surgical stimulation can activate microglia, resulting in the excessive release of various inflammatory mediators, including matrix metalloproteinase-9 (MMP-9), lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-\u0026alpha;). These bioactive substances may exert neurotoxic effects by inducing blood-brain barrier dysfunction and promoting the aggregation of pro-inflammatory factors, ultimately leading to cognitive decline [19]. Research data indicate that, compared to the control group, the experimental group receiving thoracic paravertebral block (TPVB) combined with opioid-lidocaine infusion (OLI) exhibited a significant reduction in the aforementioned inflammatory markers at various postoperative time points, demonstrating that this combined regimen effectively inhibits surgery-induced neuroinflammatory responses. To ensure the accuracy of cognitive function assessments, the research team conducted cognitive function tests 24 hours preoperatively and on the 7th postoperative day, by which time the anesthetic drugs had largely been metabolized, thereby minimizing the interference of drug residues on the evaluation results. On the 7th postoperative day, the Montreal Cognitive Assessment (Moca) scores of the experimental group showed a statistically significant improvement compared to the control group, validating the unique advantages of the combined TPVB and OLI strategy in inhibiting neuroinflammation and preserving cognitive function. From the perspective of the mechanism of action, the neuroprotective effects of the TPVB-OLI combination therapy may arise from several pathways. Firstly, TPVB selectively blocks nerve conduction in the surgical area, effectively minimizing the risk of mechanical damage to neural tissues during the operation. Secondly, TPVB may significantly inhibit the production and release of inflammatory mediators by modulating key upstream signaling pathways involved in neuroinflammatory responses. Lastly, as a novel opioid, OLI not only exhibits a rapid onset and a short metabolic half-life but also enhances the safety of clinical application due to its lower incidence of respiratory depression and gastrointestinal adverse reactions. The synergistic effects of these two treatment modalities may operate through multiple mechanisms, significantly alleviating postoperative pain symptoms and thereby reducing the negative impact of pain-related stress responses on cognitive functions.\u003c/p\u003e\n\u003cp\u003eThis study confirms that, compared to TPVB combined with conventional patient-controlled intravenous analgesia, the combination of TPVB and OLI demonstrates superior analgesic efficacy in elderly patients undergoing radical lung cancer surgery. Furthermore, it effectively suppresses postoperative neuroinflammation and positively impacts cognitive function. The incidence of adverse reactions associated with this combined regimen is low, and its safety profile is favorable, indicating its potential as a preferred option for postoperative pain management and its clinical promotion value. However, limitations such as a small sample size and short follow-up duration necessitate subsequent research to conduct larger-scale, multicenter, long-term follow-up clinical trials to validate these findings and explore its application prospects in other surgical fields. Additionally, a deeper understanding of the mechanisms by which this regimen alleviates neuroinflammation and protects cognitive function will provide a more robust theoretical basis for clinical practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Xuzhou First People\u0026apos;s Hospital (Approval No: XYY11[2024]029) and registered as a clinical trial with the registration number ChiCTR2400090498. All participants provided written informed consent before any study-related procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the following grants:\u003c/p\u003e\n\u003cp\u003e- Xuzhou Municipal Medical and Health General Project (2023) (KC23160)\u003c/p\u003e\n\u003cp\u003e- Xuzhou Medical University Affiliated Hospital Development Fund Project (XYFM202236)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eY.L. (Yang Li): conception and design of the study, acquisition of funding, drafting the manuscript, final approval.J.N.N. (Ji Ningning): patient recruitment, randomization, peri-operative data collection, critical revision of the manuscript.Z.J. (Zhang Jin): ultrasound-guided TPVB performance, anesthesia management, statistical analysis, preparation of tables and figures.L.B.P. (Li Beiping): neuro-cognitive assessments, biomarker measurements, interpretation of inflammatory data, revision of the discussion. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhao Ruolin L, Lili W, Dongmei, et al. Effect of perioperative low-dose esketamine on postoperative analgesia in patients undergoing radical resection of lung cancer by thoracoscopy [J]. Chin J Practical Diagnosis Therapy. 2023;37(3):269\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Yanfeng C, Minwei H. Wei. 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The control group received TPVB combined with conventional intravenous patient-controlled analgesia, while the experimental group received Oliceridine in addition to TPVB for intravenous patient-controlled analgesia. Postoperative pain was assessed using the Visual Analog Scale (VAS), and the levels of inflammatory mediators such as matrix metalloproteinase-9 (MMP-9), lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α) in plasma were measured at different time points postoperatively. Cognitive function was evaluated using the Montreal Cognitive Assessment (Moca), and the occurrence of adverse reactions was recorded in both groups. The VAS scores of the experimental group at 6 hours, 12 hours, 24 hours, and 48 hours postoperatively were significantly lower than those of the control group (P\u0026lt;0.05), indicating that the combined regimen has a good analgesic effect. At all postoperative time points, the plasma levels of MMP-9, Lp-PLA2, IL-6, and TNF-α in the experimental group were significantly lower than those in the control group (P\u0026lt;0.05), indicating that this regimen can effectively inhibit postoperative neuroinflammatory responses. On the 7th day post-surgery, the Moca score of the experimental group was significantly higher than that of the control group (P\u0026lt;0.05), suggesting that this combined regimen has a protective effect on postoperative cognitive function. Additionally, the incidence of adverse reactions in the experimental group was significantly lower than that in the control group (P\u0026lt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e[\u003cstrong\u003eConclusion\u003c/strong\u003e]: Oliceridine combined with TPVB demonstrates significant analgesic efficacy in radical surgery for elderly lung cancer patients, effectively inhibits postoperative neuroinflammatory responses, provides protective effects on postoperative cognitive function, and exhibits good safety, indicating its clinical value for promotion.\u003c/p\u003e","manuscriptTitle":"Analgesic Effect of Oliceridine Combined with Thoracic Paravertebral Nerve Block in Elderly Patients Undergoing Lung Cancer Resection and Its Impact on Neuroinflammation and Cognitive Function","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-14 14:45:14","doi":"10.21203/rs.3.rs-8500085/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-01-19T14:13:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160034138128034920849315511369748571632","date":"2026-01-18T13:28:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-13T07:24:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-05T02:20:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-05T02:20:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Geriatrics","date":"2026-01-02T10:25:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fa77a4d6-62b2-446c-afa7-e8ccd20e1f18","owner":[],"postedDate":"January 14th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-14T14:45:14+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-14 14:45:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8500085","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8500085","identity":"rs-8500085","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}