The relationship between innate/adaptive immunity and gastrointestinal cancer : a multi-omics Mendelian randomization study.

BACKGROUND: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. CONCLUSION: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.

Circadian misalignment leads to changes in cortisol rhythms, blood biochemical variables and serum miRNA profiles.

The circadian clock plays a critical role in synchronizing the inner molecular, metabolic and physiological processes to environmental cues that cycle with a period of 24 h. Non-24 h and shift schedules are commonly used in maritime operations, and both of which can disturb circadian rhythms. In this study, we first conducted an experiment in which the volunteers followed a 3-d rotary schedule with consecutive shift in sleep time (rotatory schedule), and analyzed the changes in salivary cortisol rhythms and blood variables. Next we conducted another experiment in which the volunteers followed an 8 h-on and 4-h off schedule (non-24-h schedule) to compare the changes in blood/serum variables. The rotatory schedule led to elevated levels of serum cortisol during the early stage, and the phase became delayed during the early and late stages. Interestingly, both of the schedules caused comprehensive changes in blood/serum biochemical variables and increased phosphate levels. Furthermore, transcriptomic analysis of the plasma miRNAs from the volunteers following the rotatory schedule identified a subset of serum miRNAs targeting genes involved in circadian rhythms, sleep homeostasis, phosphate transport and multiple important physiological processes. Overexpression of miRNAs targeting the phosphate transport associated genes, SLC20A1 and SLC20A2, showed altered expression due to rotary schedule resulted in attenuated cellular levels of phosphate, which might account for the changed levels in serum phosphate. These findings would further our understanding of the deleterious effects of shift schedules and help to optimize and enhance the performances and welfare of personnel working on similar schedules.

Sleep deprivation and a non-24-h working schedule lead to extensive alterations in physiology and behavior.

Most organisms on Earth possess circadian rhythms in their physiology and behaviors that allow them to resonate with the cycling environment over a 24-h period. However, in human society, a substantial quantity of jobs requires non-24-h working and rest or shift schedules, which causes more or less misalignment in circadian rhythms and disorders as a consequence. In this work, we conducted a sleep deprivation (SD) and non-24-h working and rest schedule (8 h on and 4 h off) experiment over 10 d in total and measured the changes in a series of physiologic and cognitive parameters. The results show that although the subjects could sleep during the schedule, their sleepiness increased significantly. Actigraphy data suggest that a 12-h schedule might result in chronic SD. Along with the increased sleepiness revealed by the Karolinska Sleepiness Scale questionnaire, the neurobehavioral psychomotor vigilance test data reveal that, compared with the control period, the reaction time of the subjects was significantly delayed. The saliva insulin levels were significantly changed in the morning in SD and non-24-h cycles. Salivary biochemical parameters were also altered, including aspartate aminotransferase and K+. 16S rRNA-based analysis of the salivary microbiota showed differentially changed patterns in bacteria composition and concentration. Together, these data demonstrate that an abnormal working and rest schedule might produce comprehensive interference with circadian rhythms, metabolism, and cognition.-Ma, H., Li, Y., Liang, H., Chen, S., Pan, S., Chang, L., Li, S., Zhang, Y., Liu, X., Xu, Y., Shao, Y., Yang, Y., Guo, J. Sleep deprivation and a non-24-h working schedule lead to extensive alterations in physiology and behavior.

Enhanced high-frequency precuneus-cortical effective connectivity is associated with decreased sensory gating following total sleep deprivation.

Sleep deprivation decreases an individual's cognitive function. When cognitive impairment reaches a certain level, human errors occur and may even result in accidents. Previous research has shown that sensory gating is a basic mechanism in cognitive function, but only limited studies have so far reported how it is affected by sleep deprivation. This study aimed to analyze the effects of sleep deprivation on sensory gating and its cognitive and neural mechanisms. Thirty-six healthy subjects participated in our study. The resting-state, auditory P50-task electroencephalography (EEG) recordings and the psychomotor vigilance task (PVT) were performed at resting wakefulness (RW) and after 36 h of total sleep deprivation (TSD). Changes in P50 suppression before and after sleep deprivation were recorded, and the isolated effective coherence (iCoh) was employed for analyzing effective connectivity based on EEG data during the resting-state and P50 tasks. Subjects demonstrated reduced P50 suppression and prolonged PVT reaction time after TSD compared with RW. Effective connectivity analysis of resting-state EEG data showed that sleep deprivation decreased the connectivity from the right middle occipital gyrus (RMOG)/Rcuneus to left inferior/middle temporal gyrus (LITG/LMTG) and left parahippocampal/fusiform gyrus (LPH/LFG). EEG data analysis during the P50 task showed that, in addition to the aforementioned connectivity changes, the directed high-frequency effective connectivity from the left precuneus to the left superior/middle frontal gyrus (LSFG/LMFG), LITG/LMTG, LPH/LFG, and left middle occipital gyrus (LMOG)/Lcuneus increased. P50 suppression in Cz positively correlated with PVT reaction time. This study reveals that the precuneus is a key brain region in neural network correlates of sensory gating, and that changes in its effective connectivity with other regions (including LSFG/LMFG, LPH/LFG, LMOG/LCuneus, and LITG/LMTG) are important for decreasing sensory gating after TSD.

A new psychological intervention: "512 Psychological Intervention Model" used for military rescuers in Wenchuan Earthquake in China.

OBJECTIVE: We sought to compare the efficacy of the "512 Psychological Intervention Model" (that is, "512 PIM", a new psychological intervention) with debriefing on symptoms of post-traumatic stress disorder (PTSD), anxiety and depression of Chinese military rescuers in relation to a control group that had no intervention. METHOD: We conducted a randomized controlled trial with 2,368 military rescuers 1 month after this event and then at follow-up 1, 2 and 4 months later to evaluate changes in symptoms of PTSD, anxiety and depression based on DSM-IV criteria, respectively. RESULTS: Baseline analysis suggested no significant differences between the study groups. Severity of PTSD, anxiety and depression decreased over time in all three groups, with significant differences between the groups in symptoms of PTSD (P < 0.01). Compared with the debriefing and control group, significant lower scores of PTSD and positive efficacy in improving symptoms of re-experiencing, avoidance and hyperarousal were found in the "512 PIM" group. CONCLUSION: "512 PIM" was an effective psychological intervention for military rescuers in reducing symptoms of PTSD, anxiety and depression after a crisis.

Comprehensive detrimental effects of a simulated frequently shifting schedule on diurnal rhythms and vigilance.

Accumulating data have demonstrated that shift work causes a disturbance in circadian rhythms, which is detrimental to physiology and performance. However, the detailed effects of shift work and especially the underlying mechanisms remain to be further investigated. Frequently shifting schedules are widely used in industries, e.g., maritime tasks, oil mining, and aviation. In this work, we investigated the physiological changes and vigilance of 12 subjects who lived on a 30-day frequent shift working schedule in a confined environment, which mimics the common maritime schedules. Elevated and decreased cortisol levels were observed at different stages during the shift, suggesting the occurrence of stress and fatigue. The results of the Karolinska Sleepiness Scale (KSS) indicate increased sleepiness and a changed pattern of the rhythmicity of sleepiness during the shift. The tests of the Psychomotor Vigilance Task (PVT) reveal that the shift led to a continuously decreasing alertness as the shift working schedule progressed, which is prevalently due to the increasingly slower reaction speed. The PVT time-out errors were significantly increased in the early period but decreased in the late period. In addition, we found recoupling of the correlations between multiple physiological and cognitive variables. For instance, heartbeat rate (HR) and breath rate (BR) showed moderate correlations in the control and early periods but little in the late period. Together, these results reveal substantial alterations in diurnal rhythms, affected vigilance and changed coupling of the correlations of diurnal rhythms, physiology and cognition caused by a shift schedule. Our findings may help in the recognition of the detrimental effects of such working schedules and provide clues for the development of potential mitigations.

[Effect of 36h total sleep deprivation on the object working memory: an ERP study].

Objective: To investigate the effects of 36 h total sleep deprivation (TSD) on object working memory by event related potential(ERP). Methods: We used a pre-post-design, sixteen healthy college students (age range: 21-28 years, mean age: 23 years) received object working memory tasks while awake and after 36 hours of TSD and simultaneously recording electroencephalograph (EEG) data while completing 2-back object working memory tasks. ERP data were statistically analyzed using repeated measurements analysis of variance to observe the changes in the working memory-related P2, N2 and P3 components. Results: After 36 h TSD, the latency of N2 waves related to object working memory significantly was prolonged (P＜0.05), and the amplitude was decreased, but difference did not reach statistical significance (P＞0.05). The latency of P2 was significantly prolonged after TSD (P＜0.05). There was no significant difference in the change of latency and amplitude of P3 waves (P＞0.05). Conclusion: 36 h of total sleep deprivation affected working memory-related components and impaired object working memory capacity.

Alterations in Cerebellar Functional Connectivity Are Correlated With Decreased Psychomotor Vigilance Following Total Sleep Deprivation.

Previous studies have reported significant changes in functional connectivity among various brain networks following sleep restriction. The cerebellum plays an important role in information processing for motor control and provides this information to higher-order networks. However, little is known regarding how sleep deprivation influences functional connectivity between the cerebellum and the cerebral cortex in humans. The present study aimed to investigate the changes in cerebellar functional connectivity induced by sleep deprivation, and their relationship with psychomotor vigilance. A total of 52 healthy men underwent resting-state functional magnetic resonance imaging before and after 36 h of total sleep deprivation. Functional connectivity was evaluated using region of interest (ROI)-to-ROI analyses, using 26 cerebellar ROIs as seed regions. Psychomotor vigilance was assessed using the psychomotor vigilance test (PVT). Decreased functional connectivity was observed between cerebellar seed regions and the bilateral postcentral, left inferior frontal, left superior medial frontal, and right middle temporal gyri. In contrast, increased functional connectivity was observed between the cerebellum and the bilateral caudate. Furthermore, decrease in functional connectivity between the cerebellum and the postcentral gyrus was negatively correlated with increase in PVT reaction times, while increase in functional connectivity between the cerebellum and the bilateral caudate was positively correlated with increase in PVT reaction times. These results imply that altered cerebellar functional connectivity is associated with impairment in psychomotor vigilance induced by sleep deprivation.

Bifactor item response theory model of acute stress response.

BACKGROUND: Better understanding of acute stress responses is important for revision of DSM-5. However, the latent structure and relationship between different aspects of acute stress responses haven't been clarified comprehensively. Bifactor item response model may help resolve this problem. OBJECTIVE: The purpose of this study is to develop a statistical model of acute stress responses, based on data from earthquake rescuers using Acute Stress Response Scale (ASRS). Through this model, we could better understand acute stress responses comprehensively, and provide preliminary information for computerized adaptive testing of stress responses. METHODS: Acute stress responses of earthquake rescuers were evaluated using ASRS, and state/trait anxiety were assessed using State-trait Anxiety Inventory (STAI). A hierarchical item response model (bifactor model) was used to analyze the data. Additionally, we tested this hierarchical model with model fit comparisons with one-dimensional and five-dimensional models. The correlations among acute stress responses and state/trait anxiety were compared, based on both the five-dimensional and bifactor models. RESULTS: Model fit comparisons showed bifactor model fit the data best. Item loadings on general and specific factors varied greatly between different aspects of stress responses. Many symptoms (40%) of physiological responses had positive loadings on general factor, and negative loadings on specific factor of physiological responses, while other stress responses had positive loadings on both general and specific factors. After extracting general factor of stress responses using bifactor analysis, significant positive correlations between physiological responses and state/trait anxiety (r = 0.185/0.112, p<0.01) changed into negative ones (r = -0.177/-0.38, p<0.01). CONCLUSION: Our results demonstrated bifactor structure of acute stress responses, and positive and negative correlations between physiological responses and stress responses suggested physiological responses could have negative feedback on severity of stress responses. This finding has not been convincingly demonstrated in previous research.

Positive and negative relationship between anxiety and depression of patients in pain: a bifactor model analysis.

BACKGROUND: The relationship between anxiety and depression in pain patients has not been clarified comprehensively. Previous research has identified a common factor in anxiety and depression, which may explain why depression and anxiety are strongly correlated. However, the specific clinical features of anxiety and depression seem to pull in opposite directions. OBJECTIVE: The purpose of this study is to develop a statistical model of depression and anxiety, based on data from pain patients using Hospital Anxiety and Depression Scale (HADS). This model should account for the positive correlation between depression and anxiety in terms of a general factor and also demonstrate a latent negative correlation between the specific factors underlying depression and anxiety. METHODS: The anxiety and depression symptoms of pain patients were evaluated using the HADS and the severity of their pain was assessed with the visual analogue scale (VAS). We developed a hierarchical model of the data using an IRT method called bifactor analysis. In addition, we tested this hierarchical model with model fit comparisons with unidimensional, bidimensional, and tridimensional models. The correlations among anxiety, depression, and pain severity were compared, based on both the bidimensional model and our hierarchical model. RESULTS: The bidimensional model analysis found that there was a large positive correlation between anxiety and depression (r = 0.638), and both scores were significantly positively correlated with pain severity. After extracting general factor of distress using bifactor analysis, the specific factors underlying anxiety and depression were weakly but significantly negatively correlated (r = -0.245) and only the general factor was significantly correlated with pain severity. Compared with the three first-order models, the bifactor hierarchical model had the best model fit. CONCLUSION: Our results support the hypothesis that apart from distress, anxiety and depression are inversely correlated. This finding has not been convincingly demonstrated in previous research.