MMP-9 inhibition alleviates postoperative cognitive dysfunction by improving glymphatic function via regulating AQP4 polarity.

Postoperative cognitive dysfunction (POCD) is a common complication after surgery, characterized by deficits in memory, attention and cognitive flexibility. However, the underlying mechanisms of POCD remain unclear. Neuroinflammation and blood-brain barrier disruption have been implicated as potential pathological processes. This study explores the neuroprotective effects and mechanisms of the matrix metalloproteinase（MMP-9）inhibitor GM6001 against POCD. We hypothesize GM6001 may reduce neuroinflammation and preserve blood-brain barrier integrity through direct inhibition of MMP-9. Moreover, GM6001 may stabilize aquaporin-4 polarity and glymphatic clearance function by modulating MMP-9-mediated cleavage of dystroglycan, a key protein for aquaporin-4 anchoring. Our results demonstrate GM6001 alleviates postoperative cognitive deficits and neuroinflammation. GM6001 also preserves blood-brain barrier integrity and rescues aquaporin-4 mislocalization after surgery. This study reveals a novel dual role for MMP-9 inhibition in cognitive protection through direct anti-neuroinflammatory effects and regulating aquaporin-4 membrane distribution. Targeting MMP-9 may represent a promising strategy to prevent postoperative cognitive dysfunction by integrating multiple protective mechanisms.

AQP4 is an Emerging Regulator of Pathological Pain: A Narrative Review.

Pathological pain presents significant challenges in clinical practice and research. Aquaporin-4 (AQP4), which is primarily found in astrocytes, is being considered as a prospective modulator of pathological pain. This review examines the association between AQP4 and pain-related diseases, including cancer pain, neuropathic pain, and inflammatory pain. In cancer pain, upregulated AQP4 expression in tumor cells is linked to increased pain severity, potentially through tumor-induced inflammation and edema. Targeting AQP4 may offer therapeutic strategies for managing cancer pain. AQP4 has also been found to play a role in nerve damage. Changes in AQP4 expression have been detected in pain-related regions of the brain and spinal cord; thus, modulating AQP4 expression or function may provide new avenues for treating neuropathic pain. Of note, AQP4-deficient mice exhibit reduced chronic pain responses, suggesting potential involvement of AQP4 in chronic pain modulation, and AQP4 is involved in pain modulation during inflammation, so understanding AQP4-mediated pain modulation may lead to novel anti-inflammatory and analgesic therapies. Recent advancements in magnetic resonance imaging (MRI) techniques enable assessment of AQP4 expression and localization, contributing to our understanding of its involvement in brain edema and clearance pathways related to pathological pain. Furthermore, targeting AQP4 through gene therapies and small-molecule modulators shows promise as a potential therapeutic intervention. Future research should focus on utilizing advanced MRI techniques to observe glymphatic system changes and the exchange of cerebrospinal fluid and interstitial fluid. Additionally, investigating the regulation of AQP4 by non-coding RNAs and exploring novel small-molecule medicines are important directions for future research. This review shed light on AQP4-based innovative therapeutic strategies for the treatment of pathological pain. Dark blue cells represent astrocytes, green cells represent microglia, and red ones represent brain microvasculature.

Biophilic virtual reality on children's anxiety and pain during circumcision: A randomized controlled study.

INTRODUCTION: The aim of this study was to evaluate the effects of the biophilic virtual reality (BVR) method on children's pain and anxiety undergoing circumcision. MATERIALS AND METHODS: This randomized controlled study used a parallel trial design guided by the CONSORT checklist. A total of 106 children were included in the analysis. Intraoperative anxiety was assessed by using the simplified Chinese version of the modified Yale Preoperative Anxiety Scale (CmYPAS), Visual Analogue Scale (VAS), heart rate (HR), and Anxiety index (Ai). Intraoperative pain was assessed by using the Faces Pain Scale-Revised (FPS-R), and Pain index (Pi). The Pearson correlation analysis was used to analyze the relationship between Ai and the CmYPAS. The primary outcomes were CmYPAS, VAS, and FPS-R, which were analyzed using the Kruskal-Wallis test. RESULTS: Baseline variables were not significantly different between the BVR group (34 patients), the indoor virtual reality (IVR) group (36 patients), and the blank control group (36 patients). The CmYPAS scores during surgery were significantly lower in the BVR group and the IVR group versus the blank control group (25.0[22.9-29.2], 22.9[22.9-29.2], 33.3[33.3-38.5] respectively; P < 0.001). The VAS scores during surgery were significantly lower in the BVR group and the IVR group versus the blank control group (5.0[3.0-7.0], 3.0[2.0-5.0], 6.0[5.0-8.8] respectively; P < 0.001). The FPS-R scores during surgery were significantly lower in the BVR group and IVR group versus the blank control group (2.0[1.8-4.2], 3.0[2.0-4.8], 5.5[5.0-8.0], respectively; P < 0.001). At removal of the foreskin, Pi were significantly lower in the BVR group and IVR group versus the blank control group (6.9[4.1], 7.7[3.3], 9.8[6.2] respectively; P = 0.033). The Ai scores at each time point were significantly lower in the BVR group and IVR group versus the control (P = 0.015, P = 0.006 respectively). The correlation analysis of Ai (at removal of the foreskin) and CmYPAS scores in children showed that the Pearson correlation coefficient was 0.194 (P = 0.046). DISCUSSION: This is the first RCT to investigate the effects of BVR in children undergoing circumcision. This study demonstrates a reduction in pediatric intraoperative pain and anxiety with the use of virtual reality (VR). CONCLUSION: Intraoperative VR may be an effective noninvasive modality for reducing pain and anxiety during circumcision. Pi and Ai might be used to assess subjective pain and anxiety in patients.

Modified Frailty Index Combined with a Prognostic Nutritional Index for Predicting Postoperative Complications of Hip Fracture Surgery in Elderly.

Aim: There is currently no consensus on the best risk assessment technique for predicting complications after hip surgery in the elderly, which is hindering the accuracy of surgical risk assessment. The goal of this study was to build a risk assessment model and evaluate its predictive value using the modified frailty index (5-mFI) and the prognostic nutritional index (PNI).Methods: A retrospective investigation was undertaken on 150 patients (aged ≥60 years) who had hip fracture surgery. Using univariate and multivariate logistic regression models, the relationship between combined 5-mFI and PNI and the evaluation of postoperative unfavorable outcomes such as infection and unscheduled intensive care unit (ICU) admission was investigated. Finally, utilizing receiver operating characteristic (ROC) curve analysis, the model's predictive value for adverse outcomes following hip fracture surgery in elderly patients was assessed.Results: Univariate and multivariate logistic analyses revealed that preoperative PNI, 5-mFI, ASA, and gender acted as independent predictors of adverse outcomes after hip fracture surgery in the elderly. According to the ROC curve analysis, the predictive model demonstrated a high predictive value for total postoperative complications (AUC: 0.788; 95%CI: 0.715-0.860; p<0.01), infectious complications (AUC: 0.798; 95% CI: 0.727-0.868; P<0.001), and unplanned ICU admission (AUC: 0.783; 95% CI: 0.705-0.861; P<0.001).Conclusions: The multivariable evaluation model, which included 5-mFI and PNI, showed a high predictive value and can hence be applied to predict the adverse outcomes in elderly patients undergoing hip fracture surgery.