Spatial memory requires hypocretins to elevate medial entorhinal gamma oscillations.

The hypocretin (Hcrt) (also known as orexin) neuropeptidic wakefulness-promoting system is implicated in the regulation of spatial memory, but its specific role and mechanisms remain poorly understood. In this study, we revealed the innervation of the medial entorhinal cortex (MEC) by Hcrt neurons in mice. Using the genetically encoded G-protein-coupled receptor activation-based Hcrt sensor, we observed a significant increase in Hcrt levels in the MEC during novel object-place exploration. We identified the function of Hcrt at presynaptic glutamatergic terminals, where it recruits fast-spiking parvalbumin-positive neurons and promotes gamma oscillations. Bidirectional manipulations of Hcrt neurons' projections from the lateral hypothalamus (LHHcrt) to MEC revealed the essential role of this pathway in regulating object-place memory encoding, but not recall, through the modulation of gamma oscillations. Our findings highlight the significance of the LHHcrt-MEC circuitry in supporting spatial memory and reveal a unique neural basis for the hypothalamic regulation of spatial memory.

A paraventricular thalamus to central amygdala neural circuit modulates acute stress-induced heightened wakefulness.

Heightened wakefulness in response to stressors is essential for survival but can also lead to sleep disorders like insomnia. The paraventricular thalamus (PVT) is both a critical thalamic area for wakefulness and a stress-sensitive brain region. However, whether the PVT and its neural circuitries are involved in controlling wakefulness in stress conditions remains unknown. Here, we find that PVT neurons projecting to the central amygdala (CeA) are activated by different stressors. These neurons are wakefulness-active and increase their activities upon sleep to wakefulness transitions. Optogenetic activation of the PVT-CeA circuit evokes transitions from sleep to wakefulness, whereas selectively silencing the activity of this circuit decreases time spent in wakefulness. Specifically, chemogenetic inhibition of CeA-projecting PVT neurons not only alleviates stress responses but also attenuates the acute stress-induced increase of wakefulness. Thus, our results demonstrate that the PVT-CeA circuit controls physiological wakefulness and modulates acute stress-induced heightened wakefulness.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined with Surgery: A 12-Year Meta-Analysis of this Promising Treatment Strategy for Advanced Gastric Cancer at Different Stages.

BACKGROUND: This meta-analysis was designed to systematically assess the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with surgery for different stages of advanced gastric cancer (AGC) during the last 12 years. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched online, and papers were retrieved from other sources. Next, randomized controlled trials (RCTs) and high-quality nonrandomized controlled trials (NRCTs) were selected for this analysis. The meta-analysis was conducted with RevMan5.4 software. RESULT: The 10 RCTs and 13 NRCTs selected for the study included 1892 patients. The overall survival rates were higher in the HIPEC group at 1 year (risk ratio [RR], 0.52; P = 0.004) and 3 years (RR, 0.63; P < 0.00001) than in the control group for the patients without peritoneal cancer, and the HIPEC group had a significant reduction in the recurrence rate (RR, 0.60; p < 0.00001). Among the patients with peritoneal carcinomatosis (PC), the HIPEC group had significantly higher overall survival rates at 1 year (RR, 0.62; P = 0.00001), 2 years (RR, 0.85; P = 0.002), and 3 years (RR, 0.87; P = 0.0001), with an increase in the overall median survival time of 4.67 months. The two groups showed no statistically significant difference in terms of complications for patients with PC (RR, 1.03; P = 0.93) or without PC (RR, 1.15; P = 0.51). CONCLUSION: For local AGC without PC, standard surgery combined with prophylactic HIPEC could prolong survival and reduce the recurrence rate without more complications. The prognosis of this treatment strategy for patients with PC is closely related to patient selection. Complete cytoreduction combined with therapeutic HIPEC could prolong survival.

The Factorial Structure of Trait Anxiety and Its Mediating Effect Between Mindfulness and Depression.

Background: Increasing studies have found that high trait anxiety is a key susceptibility phenotype that causes depression. Mindfulness-based interventions can target on dealing with depressogenic vulnerability effectively. Evidence indicates that trait anxiety could affect the trajectory of anti-depressive psychotherapy, and play an important role in the relationship between mindfulness and depression. Furthermore, related studies have found that trait anxiety could involve factors beyond anxiety and be a two-factor construct instead of one-dimensional concept. This viewpoint provides a new prospective for exploring the pathways of the two factors of trait anxiety in the complex relationship and further understand the potential mechanism of vulnerable personality mediated the link of mindfulness and depression. Methods: A cross-sectional survey and a preliminary intervention study were conducted. Thousand two hundred and sixty-two subjects completed a set of self-reported questionnaires that evaluated trait anxiety, mindfulness, and depressive symptoms. Twenty-Three eligible participants with depression were recruited to attend mindfulness-based cognitive training for eight weeks. The same questionnaires were completed 1 week before the training and 6 months after the training. Factor analysis was performed on the 1262-subject sample to explore and confirm the factorial structure of trait anxiety. In addition, mediating effect analysis was conducted in the two studies to test whether two factors of trait anxiety were mediators of the relationship between mindfulness and depression. Results: The exploratory factor analysis extracted two dimensions of trait anxiety, namely, trait anxiety-present factor (TA-P) and trait anxiety-absent factor (TA-A). And confirmatory factor analysis showed that the fit of the two-factor model was acceptable. Both TA-P and TA-A were significantly negatively correlated with mindfulness and positively correlated with depression, and they played a mediating role between mindfulness and depression. The two factors of trait anxiety had multiple mediating effects on the relationship between mindfulness and depression, and the mediating effect of the TA-P factor was stronger than that of the TA-A factor. Conclusion: Our results demonstrated a two-factor model of trait anxiety in the Chinese population. TA-P and TA-A played a multiple mediating role in the relationship between mindfulness and depression. The findings provide new perspectives for psychological interventions to treat depression for people with susceptible personalities. Aiming to reduce negative emotional tendencies (TA-P factor) and enhance positive cognition (TA-A factor) may achieve the early prevention and efficient treatment of depression.