Prelimbic area to lateral hypothalamus circuit drives social aggression.

Controlling aggression is a vital skill in social species such as rodents and humans and has been associated with the medial prefrontal cortex (mPFC). In this study, we showed that during aggressive behavior, the activity of GABAergic neurons in the prelimbic area (PL) of the mPFC was significantly suppressed. Specific activation of GABAergic PL neurons significantly curbed male-to-male aggression and inhibited conditioned place preference (CPP) for aggression-paired contexts, whereas specific inhibition of GABAergic PL neurons brought about the opposite effect. Moreover, GABAergic projections from PL neurons to the lateral hypothalamus (LH) orexinergic neurons mediated aggressive behavior. Finally, directly modulated LH-orexinergic neurons influence aggressive behavior. These results suggest that GABAergic PL-orexinergic LH projection is an important control circuit for intermale aggressive behavior, both of which could be targets for curbing aggression.

Depletion of PIEZO1 expression is accompanied by upregulating p53 signaling in mice with perioperative neurocognitive disorder.

As the common complications observed in surgical elder patients, perioperative neurocognitive disorders (PND) cause a series of serious perioperative health problems. However, there are no effective treatments, and the exact mechanisms are still largely unknown. In this study, transcriptome sequencing was performed to investigate the differentially expressed genes (DEGs) in the hippocampus of C57BL/6J aged mice with or without PND. Compared with the Mock group, the expression of 352, 395, and 772 genes changed significantly in the PND group at days 1, 7, and 21 after surgery, respectively. Gene ontology (GO) and gene set enrichment analysis (GSEA) showed that DEGs were mainly associated with p53 signaling. Moreover, GSEA revealed potentially p53-related DEGs such as leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1), monooxygenase DBH-like 1 (MOXD1), and piezo type mechanosensitive ion channel component 1 (PIEZO1). Furthermore, we confirmed the decreased interaction of PIEZO1 with p53 in PND, and upregulation of PIEZO1 resulted in a decrease in p53 protein levels through increased ubiquitination of p53. In conclusion, this study contributes to the knowledge of global changes in gene expression and mechanisms during PND.

Consistency of the anesthesia consciousness index versus the bispectral index during laparoscopic gastrointestinal surgery with sevoflurane anesthesia: A prospective multi-center randomized controlled clinical study.

Background: This study aimed to compare the consistency of anesthesia consciousness index (Ai) with that of bispectral index (BIS) in monitoring the depth of anesthesia (DOA) during sevoflurane anesthesia, to reveal the optimal cutoff values in different states of consciousness, and explore the stability of DOA monitoring during intraoperative injurious stimulation. Methods: We enrolled 145 patients (97 men and 48 women) from 10 medical centers. General anesthesia was induced using intravenous anesthetics and maintained with sevoflurane. Ai and BIS values were recorded. Results: The mean difference between the Ai and BIS was-0.1747 (95% confidence interval, -0.6660 to 0.3166; p = 0.4857). The regression equation of Ai and BIS from the Deming regression analysis was y = 5.6387 + 0.9067x (y is BIS, x is Ai), and the slope and intercept were statistically significant. Meanwhile, the receiver operating characteristic curve analysis of anesthesia-induced unconsciousness, loss of consciousness, and recovery of consciousness revealed that the accuracy of Ai and BIS were similar. In addition, the optimal cutoff values of the different states of consciousness were not sensitive to age, and both Ai and BIS had no correlation with hemodynamics. Conclusion: We conclude that Ai and BIS show no systematic deviation in readings with high consistency, similar accuracy, and good stability; these insights provide more data for clinical application.

Analgesic outcomes of tramadol alone and in combination with Butorphanol or Flurbiprofen Axetil after cesarean section: a retrospective study with propensity score matching analysis.

BACKGROUND: The Society for Obstetric Anesthesia and Perinatology recommends a multimodal analgesia regimen for cesarean delivery analgesia. This study aimed to compare the analgesic effects of tramadol alone and combined with butorphanol or flurbiprofen axetil after a cesarean section. METHODS: We performed a retrospective analysis based on the electronic medical records of a teaching hospital in China from January 2018 to January 2020. We collected data on demographic characteristics, anesthesia, analgesia strategy, and pain intensity postoperatively during the first 48 hours. Inadequate postoperative analgesia during this period was defined as an NRS score ≥ 4. We also collected data regarding off-bed activity and intestinal function recovery. Participants were classified into three groups according to analgesia regimens. Groups T, TF, and TB received tramadol, a mixture of tramadol and flurbiprofen axetil, and a combination of tramadol and butorphanol, respectively. Analgesic outcomes were compared using propensity score matching analysis. RESULTS: Data from 2323 cases of caesarean section were included in the analysis, and 521 pairs were matched in each group according to their propensity score. Compared with group T, The inadequate analgesia on pain at rest and pain at movement was lower in group TF (RR: 0.42, 95% CI: 0.36-0.49, P = 0.001 and RR: 0.58, 95% CI: 0.48-0.69, P < 0.001, respectively),and the incidence of inadequate control of pain at movement was higher in group TB (RR: 1.38, 95% CI: 1.22-1.55, P < 0.001). Additionally, the percentage of off-bed activity at 2 days postoperatively was higher in group TB than in groups TF and T (78.7% vs. 68.5 and 78.7% vs. 64.9%, respectively, P < 0.001). The incidence of intestinal function recovery 2 days after cesarean delivery in group TB was higher than that in group TF (73.3% vs. 66.2%, P = 0.013). CONCLUSIONS: Combining tramadol and flurbiprofen axetil could enhance the analgesic effect and be safely used for analgesia after a cesarean section. However, combining tramadol and butorphanol may produce an antagonistic effect.

The Association Between Long-Term Spicy-Food Consumption and the Incidence of Chronic Postsurgical Pain After Cesarean Delivery: An Observational Study.

Background: Our previous study found that a long-term diet incorporating spicy foods can reduce the human basal pain threshold. Capsaicin is the pungent ingredient in chili peppers. Transient receptor potential vanilloid type1 is the capsaicin receptor expressed in the oral cavity and is the primary sensory neuron of the "pain" pathway. Few studies have examined the association between long-term spicy diet and chronic postsurgical pain (CPSP). Women who underwent elective cesarean section (eCS) have consistent characteristics of CPSP. This study aimed to investigate the relationship between a long-term spicy diet and the incidence of CPSP after eCS. Methods: Participants were divided into a low frequency group (LF, numerical rating scale (NRS)<5) for spicy food consumption and a high frequency group (HF, NRS≥5) by receiver operator characteristic analysis. The primary outcome was the incidence of CPSP three months after eCS. Propensity score matching (PSM) analysis was performed between the two frequency groups. Stepwise logistic regression analysis was then performed. Results: Of the 1029 enrolled patients, data from 982 were analyzed 3 months after eCS. After PSM, the incidence of CPSP in the HF group (30.1% [108/359]) was higher than that in the LF group (19.8% [71/359]; P = 0.001). Compared with the LF group, the risk of CPSP in the HF group increased 1.61 times by 3 months (95% CI 1.18-2.20, P = 0.003). PSM results found that 1 year, the incidence of CPSP in the HF group (15.2% [56/369]) was higher than that in the LF group (8.1% [30/369], P = 0.003). Conclusion: With an NRS≥5 as a boundary, women who consumed spicy food ≥ 2 days/week were more likely to have CPSP than those who consumed spicy food < 2 days/week.

A Patient-Controlled Intravenous Analgesia With Tramadol Ameliorates Postpartum Depression in High-Risk Woman After Cesarean Section: A Randomized Controlled Trial.

Background: Postpartum depression (PPD) is a severe psychiatric disorder. Its risk is associated with the cesarean section (CS). Currently, there are few early intervention strategies for these women with PPD who underwent CS. Methods: This was a parallel-group randomized controlled trial of singleton pregnant women who underwent elective CS in a tertiary referral hospital in China from October, 2017 to September, 2019. After operation, patients received randomly tramadol patient-controlled intravenous analgesia (PCIA; 4 mg/ml; TRA group), hydromorphone PCIA (0.04 mg/ml; HYD group), or ropivacaine patient-controlled epidural analgesia (PCEA; 1.5 mg/ml; ROP group) for 48 h in a 1:1:1 ratio. Total blinding during hospitalization was not feasible due to differences between the PCEA and PCIA treatments. All investigators who performed the follow-up were blinded to the group assignment. Outcomes: A total of 1,230 patients were enrolled for eligibility. Intention-to-treat analysis showed reduced incidence of PPD in the TRA group (n = 27 [6.6%]) than that in the HYD (10.2%, OR 1.62, 95% CI 0.98~2.68; p = 0.059) and ROP groups (10.5%, OR 1.66, 95% CI 1.01~2.75; p = 0.046) at 4 weeks post-operation, however, the difference was not statistically significant (Bonferroni corrected p = 0.118, p = 0.098, respectively). Subgroup analysis in high-risk women (preoperative Edinburgh Postpartum Depression Scale [EPDS] ≥10) showed a significantly lower incidence of PPD in the TRA group (16.5%) than in the HYD (32.6%) and ROP groups (30.9%) (Bonferroni corrected p = 0.022 and p = 0.038, respectively). The per-protocol analysis yielded similar results. Reported adverse events (AEs) were mostly mild. None of the women or infant discontinued treatment due to AEs. Conclusions: Tramadol PCIA after CS in high-risk women can help to reduce the risk of PPD at 4 weeks after elective CS. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03309163?term=ETPPD&draw=2&rank=1; ClinicalTrials.gov (NCT03309163).