Triptolide Alleviates Neuropathic Pain by Inhibiting the Activation of Microglial Toll-Like Receptor 3.

BACKGROUND: Current data indicates the incidence of neuropathic pain after surgical nerve injury is as high as 50%, thus representing a major problem for patients and for the medical system. Triptolide, a traditional Chinese herb, has anti-inflammatory effects on various neurodegenerative and neuroinflammatory diseases. This agent also reduces peripheral nerve injury-induced neuropathic pain, although the mechanism underlying this effect is still unknown. MATERIALS AND METHODS: The effects of triptolide on spinal nerve ligation (SNL) injury-induced neuropathic pain was studied in an animal model using behavioral, morphological and molecular biological methods. RESULTS: Repeated administration of intrathecal triptolide was found to alleviate SNL- or Poly(I:C) (toll-like receptor 3 agonist) injection-induced mechanical allodynia without any motor impairment. The mechanism by which triptolide reduces SNL- and Poly(I:C) injection-induced microglial activation appears to be via the inhibition of OX42 expression, which is a microglial-specific marker. Intrathecal triptolide also suppressed SNL- and Poly(I:C) injection-induced expression of spinal TRIF. TRIF transmits signals from activated TLR3 and is the downstream adaptor of TLR3 in microglia. In addition, intrathecal triptolide inhibited the expression of spinal pro-inflammatory IL-1 ß following SNL or Poly(I:C) injection. CONCLUSIONS: Intrathecal triptolide can suppress the TLR3/TRIF/IL-1 ß pathway in spinal microglia following SNL. This could be the underlying mechanism by which triptolide alleviate neuropathic pain induced by peripheral nerve injury.

Hippocampal and Retrosplenial Goal Distance Coding After Long-term Consolidation of a Real-World Environment.

Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (>2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the distance to the goal in the newly learned campus, as well as in familiar environments when the future route contained many turns. By contrast retrosplenial cortex only tracked the distance to the goal in the familiar campus. All of these responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and underscore the notion that the hippocampus continues to play a role in navigation when detailed processing of the environment is needed for navigation.

The combined use of serum Raman spectroscopy and D dimer testing for the early diagnosis of acute aortic dissection.

Objectives: Acute aortic dissection (AAD) is an extremely life-threatening medical emergency, often misdiagnosed in its early stages, resulting in prolonged wait times for rescue. This study aims to identify potential serum biomarkers that can assist in the accurate diagnosis of AAD and effectively differentiate it from other conditions causing severe chest pain. Methods: A total of 122 patients with AAD and 129 patients with other severe chest pain disorders were included in the study. Serum samples were analyzed by measuring the peak intensities of Raman spectra. For each measurement, the Raman spectrum was accumulated by two accumulations (3 s per acquisition). Logistic regression and nomogram models were developed using these peak intensities as well as D-dimer levels to predict the occurrence of AAD. The clinical utilities of these models were assessed through receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) in both training and internal test cohorts. Results: The D-dimer levels of AAD patients were significantly increased, as well as higher intensities at specific Raman peaks, including 505 cm-1, 842 cm-1, 947 cm-1, 1254 cm-1, 1448 cm-1, and 1655 cm-1 when compared to non-AAD patients. Conversely, decreased intensities were observed at Raman peaks such as 750 cm-1, 1004 cm-1, 1153 cm-1, 1208 cm-1, and 1514 cm-1 in AAD patients. Least absolute shrinkage and selection operator regression analysis on the training cohort identified eight potential predictors: D-dimer along with intensity measurements at peaks such as 505 cm-1, 750 cm-1, 1153 cm-1, 1208 cm-1, 1254 cm-1, 1448 cm-1, and 1655 cm-1. The combination of these eight potential predictors demonstrated a good discriminatory performance, with an area under the curve (AUC) value of 0.928 in the training cohort and an AUC of 0.936 in the internal test cohort, outperforming the use of D-dimer alone. Furthermore, DCA curve analysis revealed that leveraging this combination of eight potential predictors would provide substantial net benefits for clinical application. Moreover, this combination significantly augmented discrimination power, as evidenced by a continuous NRI of 39.8 % and IDI of 9.95 % in the training cohort, as well as a continuous NRI of 27.1 % and IDI of 9.95 % in the internal test cohort. Conclusions: The employment of this combination of eight potential predictors effectively rules out AAD to a greater extent. This study presents a promising diagnostic strategy for early detection using optical diagnostic techniques such as Raman spectroscopy.

Olanzapine for the prevention of postoperative nausea and vomiting after gynecologic laparoscopic surgery: a randomized controlled trial.

Purpose: This study was designed to investigate the prophylactic effect of oral olanzapine in postoperative nausea and vomiting after gynecologic laparoscopic surgery. Methods: ASA I-II, aged 18-75 years, planned to undergo gynecologic laparoscopic surgery with general anesthesia in adult female patients. Using the randomized numbers table, the patients were placed in two groups. Oral olanzapine 5 mg or placebo was given 1 h before anesthesia. All patients received standard antiemetic prophylaxis with dexamethasone and granisetron. The primary outcome was nausea and/or vomiting in the 24 h after the postoperative. Results: A total of 250 patients were randomized, and 241 were analyzed. The primary outcome occurred in 10 of 120 patients (8.3%) in the olanzapine group and 23 of 121 patients (19.2%) in the placebo group (p = 0.014). According to Kaplan-Meier analysis, the probabilities of nausea and/or vomiting in the 24 h after the postoperative in the olanzapine group were lower than in the placebo group (log-rank p = 0.014). In a multivariate Cox analysis, the variables of use of olanzapine [hazard ratio (HR): 0.35, 95% confidence interval (CI): 0.16-0.79; p = 0.012] and use of vasoactive drugs (HR: 2.48, 95% CI: 1.07-5.75; p = 0.034) were independently associated with nausea and/or vomiting in the 24 h after the postoperative. Conclusion: Our data suggest that olanzapine relative to placebo decreased the risk of nausea and/or vomiting in the 24 h after gynecologic laparoscopic surgery. Trial registration: The trial was registered prior to patient enrollment at The Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj=166900, link to registry page, Principal investigator: Nanjin Chen, Date of registration: 25 April 2022).

Preventing nausea and vomiting after laparoscopic gynecological surgery: the benefits of using olanzapine Why was this study done? Despite the use of antiemetics, postoperative nausea and vomiting remain prevalent. Furthermore, patients who undergo gynecological laparoscopic surgery are at an increased risk. Therefore, this study investigated whether oral Olanzapine could reduce the incidence of nausea and vomiting after gynaecological Laparoscopy? What did the researchers do? The research team examined patients who underwent gynecological laparoscopic surgery under general anesthesia. They observed the occurrence of nausea and vomiting within 24 hours after surgery in patients who either received or did not receive Olanzapine treatment. The goal was to assess the effectiveness of Olanzapine in reducing postoperative nausea and vomiting. What did the researchers find? The addition of Olanzapine, when combined with granisetron and dexamethasone, resulted in a decreased risk of nausea and/or vomiting within the 24 hours following gynecologic laparoscopic surgery, as compared to the placebo. Administering oral Olanzapine at a dosage of 5 mg reduced the incidence of nausea and vomiting after gynecological laparoscopy from 19.2% to 8.3%. What do the findings mean? This study has identified a safe and effective medication for preventing postoperative nausea and vomiting. Implementing Olanzapine as a preventive measure can significantly reduce the incidence of nausea and vomiting following surgery, thereby enhancing the overall medical experience for patients.