Neoadjuvant chemotherapy has become one of the initial treatment modalities for advanced ovarian cancer. Previous studies have indicated that preoperative neoadjuvant chemotherapy may reduce patients’ requirements for anesthetic agents. This study aims to investigate the effect of neoadjuvant chemotherapy on post-induction hypotension. This study enrolled a total of 532 patients, with 482 included in the primary analysis. Multivariable logistic regression and propensity score matching were used to analyze the association between Neoadjuvant chemotherapy and post-induction hypotension. Multiple sensitivity analyses were performed, including the use of alternative MAP thresholds, multiple imputation, inverse probability weighting, and E-value methods. This study enrolled a total of 532 patients, of whom 482 were included in the primary analysis. After propensity score matching, each group included 161 patients. The incidence of PIH were 29.19

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

ObjectiveTo develop and validate deep learning (DL) and machine learning (ML) models based on preoperative facial images and structured clinical data for predicting hypoxemia during adult painless gastrointestinal endoscopy, addressing the limitations of subjective and data-intensive prediction methods.MethodsA total of 424 patients aged 18-80 years from the East Campus of the First Affiliated Hospital of Zhengzhou University (training/validation set) and 60 patients from the West Campus (test set) between October 2022 and October 2023 were included. A ResNet-50 DL architecture and five ML algorithms (LightGBM, XGBoost, Random Forest, Logistic Regression, were Naive Bayes) were trained. K-fold cross-validation, data augmentation, and class weighting were applied to address class imbalance. Model performance was assessed using AUC, precision-recall curves, calibration curves, confusion matrices, class activation maps, and accuracy.ResultsResNet-50 achieved the highest AUC of 0.8967 (95% CI: 0.8598-0.9402) and accuracy of 0.8500 (95% CI: 0.7333-0.9167), outperforming all ML models. LightGBM was the best ML performer (AUC: 0.8304; accuracy: 0.8176).ConclusionsThe proposed ResNet-50 model enables accurate, objective, and noninvasive prediction of hypoxemia risk using only facial images, offering a rapid preoperative risk assessment tool. This approach may enhance patient safety and streamline anesthesia workflows in outpatient endoscopy. Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2400082682ConclusionsThe proposed ResNet-50 model enables accurate, objective, and noninvasive prediction of hypoxemia risk using only facial images, offering a rapid preoperative risk assessment tool. This approach may enhance patient safety and streamline anesthesia workflows in outpatient endoscopy. Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2400082682

Although the understanding of pain mechanism and management has made substantial progress, postoperative pain relief is still an important health care problem. Surgical patients also often report preoperative and postoperative sleep problems. Clinical and experimental studies show that chronic pain and sleep disorders influence each other. Pain disturbs sleep, and sleep deprivation or sleep disorders increase pain. However, there are still many problems about the direction of causality between them and the mechanism that may explain their relationship. In-depth subjective and objective evaluation of pain and sleep supports the view that sleep disorder is a more powerful and reliable predictor of pain, and pain is a predictor of sleep disorder. Recent progress in multimodal imaging, molecular biology, and neural circuit analysis has uncovered how sleep deprivation - especially in the perioperative setting - influences pain sensitivity, the transition to chronic pain, and brain function through mechanisms spanning peripheral nerves, the spinal cord, subcortical areas, and cortical structures.

Sepsis is an infection-induced syndrome characterized by systemic immune dysregulation and has traditionally been treated primarily with antibiotics. Although antibiotics remain essential for pathogen control, they rarely reverse immune dysfunction, barrier disruption, or microbial ecological imbalance in sepsis, suggesting that a purely anti-infective paradigm may be insufficient. In such phenotypes, microbiome-centered approaches may complement conventional anti-infective strategies by supporting microbial ecological restoration, host immune recalibration and disease tolerance. There is increasing evidence that the microbiome plays an important role in sepsis pathogenesis and immune modulation, both as a byproduct of immune perturbation and as a context-dependent mediator of immune maladaptation. Such insights underpin therapeutic strategies that integrate immune reprogramming with ecological restoration beyond infection control. Recent progress in single-cell omics, spatial transcriptomics and metabolomics is starting to uncover the complex interactions between microbial communities and the host immune system, providing new conceptual and translational pathways. Precise microbiome modulation combined with targeted immune recalibration may help shape future sepsis therapy, centered on restoring immune-microbial homeostasis rather than simply suppressing inflammation.

Neuropathic pain (NP) is frequently comorbid with anxiety and depression, yet the underlying molecular mechanisms in the brain remain poorly understood, hindering the development of targeted therapies. This study aimed to identify key transcriptional networks and regulatory pathways in the anterior cingulate cortex (ACC) associated with NP-induced anxiodepression. We analyzed transcriptomic data (GSE92718) from the ACC of a mouse model of chronic NP. By comparing differentially expressed genes at a time point manifesting anxiodepressive-like behavior (8-week post-injury) against those with pain alone (2-week), we constructed a weighted gene co-expression network (WGCNA). A key module (blue module) significantly correlated with the anxiodepressive phenotype was enriched for synaptic signaling (glutamatergic/GABAergic), neuroplasticity, and key pathways like MAPK and Ras. Within this module, we identified 7 pivotal lncRNAs and 5 hub mRNAs (Flt1, Slc38a2, Bmpr1b, Pdgfra, Gng2) via integrated lncRNA-mRNA-pathway and protein-protein interaction network analyses. Furthermore, we established a competing endogenous RNA (ceRNA) network, revealing a core regulatory axis comprising 3 hub lncRNAs, 5 hub mRNAs, and 40 miRNAs. The aberrant expression of the five hub mRNAs in the ACC was specifically validated in mice with anxiodepressive phenotypes using RT-PCR. Our findings unveil a critical ceRNA network and implicate dysregulated synaptic genes in the ACC as key drivers of NP-induced anxiodepression, providing novel insights into its molecular basis and highlighting potential diagnostic biomarkers and therapeutic targets.

Sleep is crucial for sustaining normal physiological functions, and sleep deprivation has been associated with increased pain sensitivity. The histone deacetylases (HDACs) are known to significantly regulate in regulating neuropathic pain, but their involvement in nociceptive hypersensitivity during sleep deprivation is still not fully understood. Utilizing a modified multi-platform water environment technique to establish a sleep deprivation model. We measured the expression levels of HDAC1/2 in the medial prefrontal cortex (mPFC) through immunoblotting and real-time quantitative PCR. The presence of pyroptosis was determined using a TUNEL assay. Suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor employed clinically, was injected into the peritoneal cavity to inhibit HDAC2 expression. Animal pain behaviors were evaluated by measuring paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs). Our findings indicate that sleep deprivation leads to increased nociceptive hypersensitivity, an upregulation of HDAC2 expression in the mPFC, a downregulation of the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and changes in markers of oxidative stress in rats. SAHA, the HDAC inhibitor, enhanced NRF2 expression by inhibiting HDAC2, which consequently ameliorated oxidative stress and mitigated nociceptive hypersensitivity in rats. The incidence of apoptosis was found to be higher in the mPFC tissues of sleep deprivation rats, and the intraperitoneal administration of SAHA decreased this apoptosis. The co-injection of SAHA and the NRF2 inhibitor ML385 into sleep deprivation rats negated the beneficial effects of SAHA. In conclusion, HDAC2 is implicated in the induction of oxidative stress and apoptosis by suppressing NRF2 levels, thereby exacerbating nociceptive hypersensitivity in sleep deprivation rats.

Hippocampal sclerosis (HS) is a pathological condition characterized by significant loss of hippocampal neurons and gliosis. This condition represents the most common neuropathological change observed in patients with temporal lobe epilepsy (TLE) and is also found in aging individuals. TLE related to HS is the most prevalent type of drug-resistant epilepsy in adults, and its underlying mechanisms are not yet fully understood. Therefore, developing improved methods for predicting and treating drug-resistant patients with TLE-HS is crucial. Patients with TLE-HS often experience cognitive impairment and psychological comorbidities, significantly affecting their quality of life. Consequently, a thorough review of the current research status of TLE-HS is essential, focusing on its prediction, diagnosis, treatment, and underlying mechanisms. The hippocampus plays a pivotal role in memory and cognition. HS of aging (HS-Aging), a condition linked to dementia in the ultra-elderly, is marked by severe CA1 (cornu ammonis) neuronal loss and frequent transactive response DNA-binding protein of 43 kDa (TDP-43) proteinopathy, often misdiagnosed as Alzheimer's disease (AD). Nonetheless, clinical characteristics and patterns of hippocampal atrophy can help differentiate between the two disorders. This review aims to provide a comprehensive overview of the pathological features of HS, the relevant mechanisms underlying TLE-HS and HS-Aging, current imaging diagnostic techniques, including machine learning, and available treatment modalities. It also explores the prognosis and comorbidities related to these conditions. Future research directions include establishing animal models to clarify the poorly understood mechanisms underlying HS, particularly those related to emotional processing. Investigating post-HS behavioral and cognitive changes in these models will lay the foundation for further advancements in this field. This review is a cornerstone for future investigations and suggests additional research endeavors.

Objective This multicentre study aimed to develop and validate a machine learning (ML) model to predict postoperative nausea and vomiting (PONV) in patients undergoing sedated gastrointestinal endoscopy. We compared multiple algorithms, applied SHAP for feature interpretability, and translated the optimized model into a web-based tool. Methods A total of 745 patients were prospectively enrolled from four tertiary hospitals in China, including a development cohort of 428 patients from the First Affiliated Hospital of Zhengzhou University (July-December 2023) and an external validation cohort of 317 patients from three institutions (June-August 2024). Eligible patients were aged 18-80 years with ASA I-III. Exclusions included severe cardiopulmonary comorbidities, >30% missing data, complications or withdrawal. Eleven ML algorithms were trained using demographic, clinical and procedural variables. Model performance was assessed via AUC, accuracy, precision, recall, F1-score, specificity and Cohen's kappa score. Calibration and SHAP analysis were conducted, and the final model was deployed as a Streamlit-based tool. Results This study enrolled 745 patients (428 in internal training and 317 in external validation cohorts). While the incidence of PONV showed no significant inter-cohort difference (29.0% vs. 29.6%, p = .85), notable disparities existed in weight, opioid use, examination type, anaesthesia duration, smoking history and diastolic blood pressure parameters (p < .05). Among 11 ML models evaluated, linear discriminant analysis (LDA) demonstrated superior generalizability in external validation (AUC: 0.834 [95%CI, 0.761-0.927]), outperforming logistic regression and support vector machines that achieved AUC > 0.800 in internal testing. The optimally calibrated LDA model facilitated development of a real-time risk prediction (https://p9xjczqdwwf7obxf6u7jeo.streamlit.app/), with SHAP interpretability analysis identifying prior PONV history, height, examination type and opioid usage as primary predictive determinants. Conclusions LDA demonstrated superior generalizability and was implemented as a web-based risk prediction tool, enabling real-time PONV assessment and supporting individualized perioperative management.

Macroautophagy/autophagy plays a crucial role in maintaining nervous system homeostasis but its role in chronic postoperative pain (CPOP) remains poorly understood. Here, we identify impaired autophagy and the accumulation of synaptic proteins in the anterior cingulate cortex (ACC) during the maintenance of CPOP after skin/muscle incision and retraction (SMIR). Lysosomal hydrolase levels are reduced upon SMIR, accompanied by a deficiency of the lysosomal trafficking protein transmembrane protein 251 (TMEM251, also named LYSET). TMEM251 overexpression alleviates impaired autophagy, accumulation of synaptic proteins within autophagy substrates, and maintenance of CPOP in SMIR mice. Conversely, TMEM251 knockdown induces autophagy impairment, accumulation of synaptic proteins, and chronic pain phenotypes in naive mice. Autophagy dysfunction is most pronounced in CaMKIIα-positive neurons in the ACC post-surgery, resulting in their activation, which is mitigated by TMEM251 overexpression. Chemogenetic activation of CaMKIIα neurons exacerbates autophagy impairment and CPOP, while their inhibition rescues SMIR-induced autophagy and pain phenotypes. Taken together, our study highlights the close relationship between impaired autophagy and neuronal activation in the promotion of chronic postoperative pain.

Purpose:The effect of esketamine on perioperative inflammatory factors and postoperative analgesic outcomes in patients with Obstructive sleep apnea syndrome (OSAS) remains unclear. This trial assesses whether 0.25 mg · kg- esketamine during general anesthesia can reduce the inflammatory level and relieve postoperative pain in OSAS patients. Patients and Methods:96 adult patients with OSAS underwent palatopharyngoplasty under general anesthesia was included in our research. Following anesthetic introduction, subjects were randomized to either 0.25 mg · kg- esketamine (in 20mL solution; esketamine group) or an equivalent volume of saline (Control group). The primary result was the level of IL-6 and TNF-α before the infusion of esketamine, 40min, 4h, and 24h after the esketamine infusion. Secondary outcomes was NRS scores immediately after tracheal extubation, 4h after the infusion, postoperative day 1 (POD1), postoperative day 2 (POD 2) and postoperative day 7 (POD 7). Results:The esketamine group demonstrated significantly reduced IL-6 and TNF-α levels at 40 minutes post-infusion (P<0.001) and showed lower the numerical rating scale(NRS)scores with less rescue analgesia immediately after extubation (P<0.001) compared to the control group, despite prolonged extubation and post-anesthesia care unit (PACU) stay (P<0.001). Across POD1-2, the esketamine group maintained reduced NRS scores (P<0.001) and analgesic doses (P=0.021), higher quality of recovery-15 (QoR-15) scores and patient satisfaction scores (P<0.001) relative to control group. It is important to note that the significant differences in inflammatory markers and pain scores between groups were not sustained at the 24-hour assessment and on postoperative day 7, respectively, indicating transient effects. Conclusion:Intraoperative infusion of 0.25 mg·kg- esketamine provided transient suppression of inflammatory responses and reduced early postoperative pain in OSAS patients. However, these benefits were exploratory and time-limited, and must be weighed against prolonged extubation and PACU stay.

Chronic postoperative pain (CPOP) remains a significant clinical challenge, with central sensitization being an important mechanism. However, the neuronal circuit-mediated mechanisms associated with this disorder are poorly understood. Here, we identified the nucleus accumbens core (AcbC) received excitatory projections from calcium/calmodulin-dependent protein kinase II (CaMKII)-positive neurons in the anterior cingulate cortex (ACC), playing an important role in the development of CPOP. We demonstrated that the AcbC neurons displayed the enhanced responses to both non-nociceptive and nociceptive stimuli following skin/muscle incision and retraction. Furthermore, fiber photometry and electrophysiological recordings confirmed that the activity of the ACCCaMKII-AcbC pathway was also elevated after surgery. Inhibition of AcbC neurons or the ACCCaMKII-AcbC pathway alleviated pain hypersensitivity in CPOP mice, whereas their activation induced pain phenotypes in naive mice. These findings reveal critical roles for the AcbC neurons and ACCCaMKII-AcbC pathway in CPOP pathogenesis, offering potential therapeutic targets for postoperative pain management.

ObjectiveWhile the pain threshold index (PTI) holds potential as a tool for monitoring analgesia-pain equilibrium, its precision in forecasting postoperative pain in children remains unconfirmed. This study's primary aim was to assess the PTI's predictive precision for postoperative pain.MethodsChildren (aged 2–16 years) undergoing general surgery under general anesthesia were included. Within 5 min prior to the patient's emergence from surgery, data including PTI, wavelet index (WLI), heart rates (HR) and mean arterial pressure (MAP) were collected. Subsequently, a 15-min pain assessment was conducted following the patient's awakening. The accuracy of these indicators in discerning between mild and moderate to severe postoperative pain was evaluated through receiver operating characteristic (ROC) analysis.ResultsThe analysis encompassed data from 90 children. ROC analysis showed that PTI was slightly better than HR, MAP and WLI in predicting postoperative pain, but its predictive value was limited. The area under the curve (AUC) was 0.659 [0.537∼0.780] and the optimal threshold was 65[64–67]. Sensitivity and specificity were determined at 0.90 and 0.50, respectively. In a multivariable logistic regression model, a higher predictive accuracy was found for a multivariable predictor combining PTI values with gender, BMI, HR and MAP (AUC, 0.768; 95%CI, 0.669–0.866). Upon further scrutinizing the age groups, PTI's AUC was 0.796 for children aged 9–16, 0.656 for those aged 4–8, and 0.601 for younger individuals.ConclusionsPTI, when used alone, lacks acceptable accuracy in predicting postoperative pain in children aged 2 to 16 years. However, when combined with other factors, it shows improved predictive accuracy. Notably, PTI appears to be more accurate in older children.

The primary aim of this research was to explore the functions of Wtap and Ythdf1 in regulating neuronal Lipocalin-2 (Lcn2) through m6A modification in traumatic brain injury (TBI). By employing transcriptome sequencing and enrichment analysis, we identified the Wtap/Ythdf1-mediated Lcn2 m6A modification pathway as crucial in TBI. In our in vitro experiments using primary cortical neurons, knockout of Wtap and Ythdf1 led to the inhibition of Lcn2 m6A modification, resulting in reduced neuronal death and inflammation. Furthermore, overexpression of Lcn2 in cortical neurons induced the activation of reactive astrocytes and M1-like microglial cells, causing neuronal apoptosis. In vivo experiments confirmed the activation of reactive astrocytes and microglial cells in TBI and importantly demonstrated that Wtap knockdown improved neuroinflammation and functional impairment. These findings underscore the significance of Wtap/Ythdf1-mediated Lcn2 regulation in TBI secondary injury and suggest potential therapeutic implications for combating TBI-induced neuroinflammation and neuronal damage.

Purpose:Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Patients and Methods:A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction. Results:Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction. Conclusion:A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Clinical Trial Registration:ChiCTR2400080363.

Background Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. Methods Pediatric patients ( n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. Results In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group ( P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively ( P = 0.021). Conclusions The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. Trial registration Chinese Clinical Trial Registry - ChiCTR2300073879 (24/07/2023).

Background: Repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) and transcutaneous electrical nerve stimulation (TENS) have both been demonstrated as effective at alleviating neuropathic pain (NP). However, the comparative efficacy of these two neuromodulation techniques and the specific neural mechanisms underlying their effects remain unclear.Objective: This study aims to compare the efficacy of rTMS in the PFC and TENS in mitigating peripheral NP and to investigate the impact of rTMS on neuroinflammation.Methods: Eighteen adult male Sprague-Dawley rats were randomly divided into three groups: NP (chronic constriction injury [CCI] group, n = 6), rTMS (n = 6), and TENS (n = 6). rTMS was applied to the PFC, while TENS was applied to the right hind limb of the rats 1 week postoperatively. This treatment regimen was administered once daily, 5 days a week, for 4 consecutive weeks. The paw withdrawal mechanical threshold (PWMT) was measured to assess the pain-alleviating effects of rTMS and TENS. We further conducted enzyme-linked immunosorbent assays (ELISAs) to measure the levels of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) in the PFC and L4-L6 spinal cord to evaluate their impact on neuroinflammation. Additionally, we examined transient receptor potential vanilloid type 1 (TRPV1) expression in the PFC and the L4-L6 spinal cord using western blotting and real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to explore the potential mechanisms involved. Hematoxylin and eosin (H&E) staining of the sciatic nerve was further performed to observe pathological changes.Results: Compared to the CCI group, both the rTMS and TENS groups exhibited a significant increase in PWMT, with the rTMS group demonstrating a notably greater PWMT than the TENS group. Furthermore, rTMS treatment triggered a significant decrease in IL-1 beta, IL-6, and TNF-alpha levels in the PFC and spinal cord, while TENS only decreased IL-1 beta expression in these regions. In both treatment groups, TRPV1 expression was significantly lower in the spinal cord, while H&E staining indicated improved pathological manifestations in the sciatic nerve.Conclusion: Both rTMS and TENS effectively ameliorated CCI-induced NP, with rTMS of the PFC showing superior performance. Both treatments reduced TRPV1 expression and suppressed neuroinflammation in the spinal cord, indicating that this may be one of the mechanisms through which they exert their therapeutic effects.

STUDY OBJECTIVES:We conducted a non-inferiority study to assess the postoperative quality of recovery (QoR) in elderly patients receiving ciprofol or propofol total intravenous anesthersia(TIVA)after elective laparoscopic major abdominal surgery, with QoR-15 scores as the main measure. DESIGN:A prospective, double-blind, randomized non-inferiority trial was conducted in the theater, post-anesthesia care unit (PACU), and the ward. PARTICIPANTS:144 elderly patients (age ≥ 65 years) were randomly assigned to either the ciprofol group or the propofol group. INTERVENTIONS:The ciprofol group received continuous infusion of ciprofol with remifentanil, and the propofol group received infusion of propofol with remifentanil. OUTCOME MEASURES:The primary outcome was the QoR-15 on the first postoperative day (POD1), assessed in both intention-to-treat and per-protocol populations, with the mean difference between groups compared to a non-inferiority threshold of -8. Additional assessments included QoR-15 scores on POD2, 3, and 5 for both analysis sets. Other evaluated perioperative value factors included hemodynamic parameters and injection discomfort in the intention-to-treat analysis. A linear mixed model was utilized to examine the impact of group-time interactions on hemodynamic data and QoR-15. MAIN RESULTS:The QoR-15 scores on POD1 in the ciprofol group were non-inferior to those in the propofol group both in intention-to-treat set (mean [95 %CI], 95.9[93.7-98.2] vs. 95.6 [93.3-97.8]; mean difference [95 % CI], 0.4 [-2.8-3.5]; P<0.001 for noninferiority) and per-protocol set (mean [95 %CI], 96.7 [94.4-99.0] vs. 95.7 [93.4-98.0]; mean difference [95 % CI], 1.0 [-2.2-4.3]; P<0.001 for noninferiority). Comparable outcomes were noted on postoperative days 2, 3, and 5 following the procedure in both analysis sets. Additionally: compared with propofol group, the occurrence of injection pain was lower (2.8 % vs. 27.8 %, P < 0.001); the hypotension was less frequent (33.3 % vs. 54.2 %, P = 0.012); the bradycardia was more common (38.9 % vs. 23.6 %, P = 0.048). CONCLUSIONS:Ciprofol is not inferior to propofol in QoR. Ciprofol can be suitably administered to elderly patients undergoing elective laparoscopic major abdominal surgery.

Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD. Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1. Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1β in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1β and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus. Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD.