Establishing the relationship between subjective perception and neural responses: Insights from Correlation Analysis and Representational Similarity Analysis.

Exploring the relationship between sensory perception and brain responses holds important theoretical and clinical implications. However, commonly used methodologies like correlation analysis performed either intra- or inter- individually often yield inconsistent results across studies, limiting their generalizability. Representational similarity analysis (RSA), a method that assesses the perception-response relationship by calculating the correlation between behavioral and neural patterns, may offer a fresh perspective to reveal novel findings. Here, we delivered a series of graded sensory stimuli of four modalities (i.e., nociceptive somatosensory, non-nociceptive somatosensory, visual, and auditory) to 107 healthy subjects and collected their single-trial perceptual ratings and electroencephalographic (EEG) responses. We examined the relationship between sensory perception and brain responses using within- and between-subject correlation analysis and RSA, and assessed their stability across different numbers of subjects and trials. We found that within-subject and between-subject correlations yielded distinct results: within-subject correlation revealed strong and reliable correlations between perceptual ratings and most brain responses, while between-subject correlation showed weak correlations that were vulnerable to the change of subject number. In addition to verifying the correlation results, RSA revealed some novel findings, i.e., correlations between behavioral and neural patterns were observed in some additional neural responses, such as "γ-ERS" in the visual modality. RSA results were sensitive to the trial number, but not to the subject number, suggesting that consistent results could be obtained for studies with relatively small sample sizes. In conclusion, our study provides a novel perspective on establishing the relationship between behavior and brain activity, emphasizing that RSA holds great promise as a method for exploring this pattern relationship in future research.

Efficacy of Endoscopic Tissue Adhesive in Patients with Gastrointestinal Tumor Bleeding.

BACKGROUND: Gastrointestinal tumors bleeding remains a significantly clinical challenge due to its resistance to conventional endoscopic hemostasis methods. While the efficacy of endoscopic tissue adhesives (ETA) in variceal bleeding has been established, its role in gastrointestinal tumor bleeding (GITB) remains ambiguous. AIMS: This study aims to assess the feasibility and effectiveness of ETA in the treatment of GITB. METHODS: The study enrolled 30 patients with GITB who underwent hemostasis through Histoacryl® tissue glue injection. Hemostasis success rates, ETA-related adverse events, and re-bleeding rates were evaluated. RESULTS: ETA application achieved successful hemostasis at all tumor bleeding sites, with immediate hemostasis observed in all 30 (100.0%) patients. Among the initially hemostasis cases, 5 patients (17.0%) experienced re-bleeding within 30 days, and the 60 day re-bleeding rate was 20.0% (6/30). Expect for one case of vascular embolism, no adverse events related with ETA application were reported. The 6 month survival was 93%. CONCLUSION: ETA demonstrated excellent immediate hemostasis success rate in GITB cases and showed promising outcomes in prevention re-bleeding.

Circ-EIF3I Promotes Hepatocellular Carcinoma Progression Through Modulating miR-361-3p/DUSP2 Axis.

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers globally. Circular RNAs (circRNAs) have been implicated in the development of HCC. Previous studies have confirmed that circ-EIF3I plays an important role in the progress of lung cancer. Nevertheless, the biological functions of circ-EIF3I and the underlying mechanisms by which they regulate HCC progression remain unclear. In this study, the regulatory mechanism and targets were studied with bioinformatics analysis, luciferase reporting analysis, transwell migration, Cell Counting Kit-8, and 5-Ethynyl-2'-deoxyuridine analysis. In addition, in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circ-EIF3I in HCC. The result shows that the circ-EIF3I expression was increased in HCC cell line, which means that circ-EIF3I plays a role in the progression of HCC. Downregulation of circ-EIF3I suppressed HCC cells' proliferation and migration in both in vivo and in vitro experiments. Bioinformatics and luciferase report analysis confirmed that both miR-361-3p and Dual-specificity phosphatase 2 (DUSP2) were the downstream target of circ-EIF3I. The overexpression of DUSP2 or inhibition of miR-361-3p restored HCC cells' proliferation and migration ability after silence circ-EIF3I. Taken together, our study found that downregulation of circ-EIF3I suppressed the progression of HCC through miR-361-3p/DUSP2 Axis.

Pain-preferential thalamocortical neural dynamics across species.

Searching for pain-preferential neural activity is essential for understanding and managing pain. Here, we investigated the preferential role of thalamocortical neural dynamics in encoding pain using human neuroimaging and rat electrophysiology across three studies. In study 1, we found that painful stimuli preferentially activated the medial-dorsal (MD) thalamic nucleus and its functional connectivity with the dorsal anterior cingulate cortex (dACC) and insula in two human functional magnetic resonance imaging (fMRI) datasets (n = 399 and n = 25). In study 2, human fMRI and electroencephalography fusion analyses (n = 220) revealed that pain-preferential MD responses were identified 89-295 ms after painful stimuli. In study 3, rat electrophysiology further showed that painful stimuli preferentially activated MD neurons and MD-ACC connectivity. These converging cross-species findings provided evidence for pain-preferential thalamocortical neural dynamics, which could guide future pain evaluation and management strategies.

Enhancing pain modulation: the efficacy of synchronous combination of virtual reality and transcutaneous electrical nerve stimulation.

Introduction: Virtual reality (VR) and transcutaneous electrical nerve stimulation (TENS) have emerged as effective interventions for pain reduction. However, their standalone applications often yield limited analgesic effects, particularly in certain painful conditions. Aims: Our hypothesis was that the combination of VR with TENS in a synchronous manner could produce the best analgesic effect among the four experimental conditions. Methods: To address this challenge, we proposed a novel pain modulation strategy that synchronously combines VR and TENS, aiming to capitalise on both techniques' complementary pain modulation mechanisms. Thirty-two healthy subjects participated in the study and underwent three types of interventions: VR alone, a combination of VR with conventional TENS, and a combination of VR with synchronous TENS. Additionally, a control condition with no intervention was included. Perceived pain intensity, pain unpleasantness, positive and negative affect scores, and electroencephalographic (EEG) data were collected before and after the interventions. To delve into the potential moderating role of pain intensity on the analgesic efficacy of VR combined with synchronous TENS, we incorporated two distinct levels of painful stimuli: one representing mild to moderate pain (ie, low pain) and the other representing moderate to severe pain (ie, high pain). Results: Our findings revealed that both combination interventions exhibited superior analgesic effects compared with the VR-alone intervention when exposed to low and high pain stimuli. Notably, the combination of VR with synchronous TENS demonstrated greater analgesic efficacy than the combination of VR with conventional TENS. EEG data further supported these results, indicating that both combination interventions elicited a greater reduction in event-related potential magnitude compared with the VR-alone intervention during exposure to low and high pain stimuli. Moreover, the synchronous combination intervention induced a more significant reduction in N2 amplitude than the VR-alone intervention during exposure to low pain stimuli. No significant differences in EEG response changes were detected between the two combination interventions. Both combination interventions resulted in a greater reduction in negative affect compared with the VR-alone intervention. Conclusions: Altogether, our study highlights the effectiveness of the synchronous combination of VR and TENS in enhancing pain modulation. These findings offer valuable insights for developing innovative pain treatments, emphasising the importance of tailored and multifaceted therapeutic approaches for various painful conditions.

Long-term post-traumatic stress symptoms in COVID-19 survivors and its risk factors: a two-year longitudinal cohort study.

The COVID-19 pandemic has led to widespread mental health problems, necessitating the investigation of longitudinal mental health changes, associated risk factors, and neural mechanisms in survivors. We recorded demographics, mental health, social support, and potential exposures in survivors at 3 months (n = 189), 6 months (n = 47), and 2 years (n = 69) post-discharge and collected brain imaging data at the second timepoint. Control groups included non-COVID-19 locals (3 months: n = 188, 6 months: n = 42, 2 years: n = 71). Results indicated that female survivors exhibited higher post-traumatic stress symptoms (PTSS) and depression levels than female controls for up to 2 years, along with higher anxiety level for up to 6 months. Male survivors had higher PTSS, depression, and anxiety levels than male controls at 2 months. Moreover, COVID-related trauma and low social support were risk factors for PTSS and negative emotions in survivors. Neuroimaging revealed increased amygdala activity in male survivors and correlations between hippocampus activity and depression symptoms as well as between right hippocampus activity and social support. Our study emphasized the importance of monitoring mental wellness in COVID-19 survivors and underscored the crucial role of social support in mitigating mental health problems.

Altered functional connectivity of the thalamus in patients with insomnia disorder after transcutaneous auricular vagus nerve stimulation therapy.

The pathogenesis of insomnia is related to the dysfunction of the thalamus. Transcutaneous auricular vagus nerve stimulation (taVNS) has proved to be effective in treating insomnia. However, whether taVNS alleviates insomnia through modulating thalamus-related functional connectivity remains unclear. To elucidate the instant modulating effects of taVNS on the resting state functional connectivity (RSFC) of the thalamus, 20 patients with insomnia disorder were recruited to receive taVNS treatment and their resting state functional magnetic resonance imaging (fMRI) data were collected immediately before and after stimulation. The fMRI data were compared with 20 age- and gender-matched healthy subjects who received no stimulation and had RSFC fMRI data collected once. RSFC analyses of the thalamus were performed in both groups. In addition to assessing the group differences between ID patients and healthy controls regarding the RSFC of the thalamus, we examined the taVNS-induced changes of RSFC of the thalamus in ID patients. Before taVNS treatment, the ID patients showed increased RSFC of the thalamus with the right insula and inferior frontal gyrus than healthy controls. After taVNS treatment, the RSFC between the thalamus and the right angular gyrus, left anterior cingulate gyrus, and precuneus were significantly decreased in patients. This study provides insights into the instant brain effects involving the thalamus-related functional connectivity of taVNS performed on insomnia disorder patients.

Effect of perioperative high-dose transdermal nicotine patch on pain sensitivity among male abstinent tobacco smokers undergoing abdominal surgery: A randomized controlled pilot study.

BACKGROUND AND AIMS: Previous studies have focused on the role of perioperative nicotine replacement therapy (NRT) in improving the success rate of long-term smoking cessation in tobacco smokers. This study aimed to measure the effectiveness of high-dose NRT in alleviating postoperative pain for male abstinent smokers receiving abdominal surgery. DESIGN: This was a parallel-group, randomized, double-blind and controlled pilot trial. SETTING AND PARTICIPANTS: In total, 101 male smoking-abstinent patients from the Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from 8 October 2018 to 10 December 2021. INTERVENTIONS: Patients started smoking cessation on admission to the hospital ward. Patients received 24-hour transdermal nicotine patches (n = 50) or placebo (n = 51) every day from admission until 48 hours after surgery. MEASUREMENTS: The primary outcomes were pre-surgery pain thresholds and total consumption of analgesics within the first 48 hours after surgery. Secondary outcomes included postoperative pain and sedation scores, nausea, vomiting and fever frequency within the treatment period. FINDINGS: Both pre-surgery electrical and mechanical pain thresholds in the NRT group were higher than those in the placebo group (P = 0.004 and P = 0.020, respectively). The 48-hour postoperative analgesic consumption was significantly lower for smoking-abstinent patients receiving NRT than those receiving placebo (standardized morphine equivalent requirement, median [interquartile range], 1.80 [1.47, 2.32] mg/kg vs 2.22 [1.62, 2.82] mg/kg, P = 0.011). Postoperative pain intensity was significantly lower in the NRT group than that in the placebo group at 1st hour and 24th hour post-surgery (P < 0.001 and P = 0.012, respectively). The incidence of treatment-related adverse events was not significantly different between groups. CONCLUSIONS: Perioperative high-dose nicotine replacement therapy may help to relieve postoperative pain among male smoking-abstinent patients undergoing abdominal surgery.

Neural processes responsible for the translation of sustained nociceptive inputs into subjective pain experience.

Tracking and predicting the temporal structure of nociceptive inputs is crucial to promote survival, as proper and immediate reactions are necessary to avoid actual or potential bodily injury. Neural activities elicited by nociceptive stimuli with different temporal structures have been described, but the neural processes responsible for translating nociception into pain perception are not fully elucidated. To tap into this issue, we recorded electroencephalographic signals from 48 healthy participants receiving thermo-nociceptive stimuli with 3 different durations and 2 different intensities. We observed that pain perception and several brain responses are modulated by stimulus duration and intensity. Crucially, we identified 2 sustained brain responses that were related to the emergence of painful percepts: a low-frequency component (LFC, < 1 Hz) originated from the insula and anterior cingulate cortex, and an alpha-band event-related desynchronization (α-ERD, 8-13 Hz) generated from the sensorimotor cortex. These 2 sustained brain responses were highly coupled, with the α-oscillation amplitude that fluctuated with the LFC phase. Furthermore, the translation of stimulus duration into pain perception was serially mediated by α-ERD and LFC. The present study reveals how brain responses elicited by nociceptive stimulation reflect the complex processes occurring during the translation of nociceptive information into pain perception.

Sex difference in trait empathy is encoded in the human anterior insula.

Females are considered the more empathic sex. This conventional view, however, has been challenged in the past few decades with mixed findings. These heterogeneous findings could be caused by the fact that empathy is a complex and multifaceted construct. To clarify whether sex differences exist in certain dimensions of empathy and whether they are associated with specific neural bases, this study measured trait empathy using the interpersonal reactivity index (IRI) and collected brain structural and functional magnetic resonance imaging data in a large sample of healthy participants (206 males vs. 302 females). We found that females scored higher in the personal distress (PD) subscale than males, but they were comparable to males in other IRI subscales. Sex difference in PD was encoded by brain structural (e.g. gray matter volume in left anterior insula [AI]) and functional (e.g. resting-state functional connectivity between left AI and temporoparietal junction/inferior frontal gyrus) characteristics. Notably, the relationship between sex and PD was indirect-only and serially mediated by AI-associated structural and functional characteristics. Altogether, our results suggested that sex difference existed in self-oriented affective empathy (i.e. PD) and highlighted the importance of the AI, both structurally and functionally, in mediating the sex difference in trait empathy.

Transcutaneous Auricular Vagus Nerve Stimulation Modulates the Prefrontal Cortex in Chronic Insomnia Patients: fMRI Study in the First Session.

Objectives: Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear. Methods: Total twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes. Results: The scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment. Conclusions: It manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.

The Effect of Tramadol Versus Sufentanil on Controlling Postoperative Pain for Men Who Smoke and Do Not Smoke: A Randomized Clinical Trial.

BACKGROUND: Smoking behavior alters the analgesic threshold, which challenges postoperative pain management for patients who smoke. OBJECTIVES: We aimed to assess the analgesic efficacy of tramadol versus sufentanil in relieving postoperative pain for patients who do and do not smoke who underwent a partial hepatectomy. STUDY DESIGN: Double-blinded randomized controlled trial. SETTING: Eastern Hepatobiliary Surgery Hospital, Shanghai, China. METHODS: All patients in this study were men. A total of 66 patients who smoke were randomly assigned to receive tramadol or sufentanil (n = 33 each). In addition, a total of 66 patients who do not smoke were randomly assigned to receive tramadol or sufentanil (n = 33 each). The primary outcome was the consumption of additional analgesics within the first 48 hours to control postoperative pain. Secondary outcomes included the postoperative pain level, the frequency of postoperative nausea and vomiting, the sedation score, and the frequency of fever within 48 hours postsurgery. RESULTS: A significant interaction between "analgesic strategy" and "smoking history" was detected on the consumption of additional analgesics. In those who smoke, the requests for additional doses of analgesics were significantly less in those receiving tramadol than those receiving sufentanil; such a difference was not observed in those who do not smoke. The postoperative pain level was not significantly different between the tramadol group and the sufentanil group within patients who smoke within 48 hours postsurgery. The incidence of treatment-related adverse events was not significantly different between the tramadol group and the sufentanil group within both those who do and do not smoke. LIMITATIONS: Only men patients were included. Also, the superior analgesic effect and the incidence of adverse events of tramadol in patients who smoke were only assessed within the first 48 hours postsurgery. CONCLUSIONS: Our data suggest that tramadol has a better analgesic effect than sufentanil in relieving postoperative pain in patients who smoke.

[Central neural mechanism of increased pain sensitivity induced by nicotine abstinence].

Nicotine is the main addictive component in cigarettes that motivates dependence on tobacco use for smokers and makes it difficult to quit through regulating a variety of neurotransmitter release and receptor activations in the brain. Even though nicotine has an analgesic effect, clinical studies demonstrated that nicotine abstinence reduces pain threshold and increases pain sensitivity in smoking individuals. The demand for opioid analgesics in nicotine abstinent patients undergoing surgery has greatly increased, which results in many side effects, such as nausea, vomiting, and respiratory depression, etc. In addition, these side effects would hinder patients' physical and psychological recovery. Therefore, identifying the neural mechanism of the increase of pain sensitivity induced by nicotine abstinence and deriving a way to cope with the increased demand for postoperative analgesics would have enormous basic and clinical implications. In this review, we first discussed different experimental pain stimuli (e.g., cold, heat, and mechanical pain)-induced pain sensitivity changes after a period of nicotine dependence/abstinence from both animal and human studies. Then, we summarized the effects of the brain neurotransmitter release (e.g., serotonin, norepinephrine, endogenous opioids, dopamine, and γ-aminobutyric acid) and their corresponding receptor activation changes after nicotine abstinence on pain sensitivity. Finally, we discussed the limits in recent studies. We proposed that more attention should be paid to human studies, especially studies among chronic pain patients, and functional magnetic resonance imaging might be a useful tool to reveal the mechanisms of abstinence-induced pain sensitivity changes. Besides, considering the influence of duration of nicotine dependence/abstinence and gender on pain sensitivity, we proposed that the effects of nicotine abstinence and individual differences (e.g., duration of abstinence from smoking, chronic/acute abstinence, and gender) on abstinence-induced pain sensitivity should be fully considered in formulating pain treatment protocols. In summary, this paper could deepen our understanding of nicotine abstinence-induced pain sensitivity changes and its underlying neural mechanism, and could also provide effective scientific theories to guide clinical pain diagnosis and treatment, which has important clinical significance.

The role of negative emotions in sex differences in pain sensitivity.

Pain perception varies widely among individuals due to the varying degrees of biological, psychological, and social factors. Notably, sex differences in pain sensitivity have been consistently observed in various experimental and clinical investigations. However, the neuropsychological mechanism underlying sex differences in pain sensitivity remains unclear. To address this issue, we quantified pain sensitivity (i.e., pain threshold and tolerance) using the cold pressure test and negative emotions (i.e., pain-related fear, pain-related anxiety, trait anxiety, and depression) using well-established questionnaires and collected magnetic resonance imaging (MRI) data (i.e., high-resolution T1 structural images and resting-state functional images) from 450 healthy subjects. We observed that, as compared to males, females exhibited lower pain threshold and tolerance. Notably, sex differences in pain sensitivity were mediated by pain-related fear and anxiety. Specifically, pain-related fear and anxiety were the complementary mediators of the relationship between sex and pain threshold, and they were the indirect-only mediators of the relationship between sex and pain tolerance. Besides, structural MRI data revealed that the amygdala subnuclei (i.e., the lateral and basal nuclei in the left hemisphere) volumes were the complementary mediators of the relationship between sex and pain-related fear, which further influenced pain sensitivity. Altogether, our results provided a comprehensive picture of how negative emotions (especially pain-related negative emotions) and related brain structures (especially the amygdala) contribute to sex differences in pain sensitivity. These results deepen our understanding of the neuropsychological underpinnings of sex differences in pain sensitivity, which is important to tailor a personalized method for treating pain according to sex and the level of pain-related negative emotions for patients with painful conditions.

Cyclin-dependent kinase like 3 promotes triple-negative breast cancer progression via inhibiting the p53 signaling pathway.

It has been reported that cyclin-dependent kinase like 3 (CDKL3) plays a crucial role in cell proliferation and migration in several cancers. However, the function of CDKL3 in triple-negative breast cancer (TNBC) is still unclear. In the present study, immunohistochemistry (IHC) was conducted to detect the CDKL3 expression. CCK-8, flow cytometry, Transwell assays, and mice xenograft models, were performed to explore the roles of CDKL3 on the proliferation and migration of TNBC in vitro and in vivo. Besides, protein chip analysis was used to screen the potential pathways, which was further confirmed by promoter activity assay, western blotting, and CCK-8 assay. Our findings reveal a high expression of CDKL3 in TNBC tissues, which is closely related to a poor prognosis of patients with TNBC. In TNBC cells, CDKL3 knockdown inhibits cell proliferation and migration, whereas CDKL3 overexpression has exactly the opposite effect. Consistently, CDKL3 knockdown induces cell apoptosis in vitro but suppresses tumor growth in vivo. Furthermore, CDKL3 knockdown increases p53 expression and reduces cell viability, and these effects are significantly weakened by the p53 inhibitor, PFT-α. In conclusion, the current study highlights that CDKL3 promotes TNBC progressions via regulating the p53 signaling pathway, suggesting that CDKL3 is a novel therapeutic target for TNBC treatment.

Serum IL-5 and IFN-γ Are Novel Predictive Biomarkers for Anti-PD-1 Treatment in NSCLC and GC Patients.

BACKGROUND: Because responses of patients with cancer to immunotherapy can vary in success, effective biomarkers are urgently needed for predicting clinical response with anti-PD-1 treatment. We aimed to evaluate the IL-5 and IFN-γ level with the response of anti-PD-1 blockade in non-small-cell lung cancer (NSCLC) and gastric cancer (GC). METHODS: Metastatic NSCLC and GC patients treated with anti-PD-1 monoclonal antibody were studied. Blood samples were taken before PD-1 McAb treatment, after the first cycle treatment, and during efficacy evaluation. The association between IL-5 and IFN-γ levels and clinical response were analyzed by the nonparametric Wilcoxon matched-pairs ranked tests. The progression-free survival (PFS) time was obtained by imaging evaluation and telephone follow-up of all the patients. Kaplan-Meier and the log rank test were used to plot the survival curve. RESULTS: IL-5 and IFN-γ levels were detected in the peripheral blood of 40 NSCLC and 35 GC patients who have received anti-PD-1 treatment. In effective group, IL-5 and IFN-γ levels at best response points significantly decreased (P < 0.001) compared with pretherapeutic levels in NSCLC and GC patients with lymph node or distant metastasis. Compared with pretherapeutic levels, IL-5 and IFN-γ levels largely increased as the tumor progresses (P < 0.01). Higher IL-5 and IFN-γ levels before treatment indicated shorter progression-free survival in patients with NSCLC metastasis (P = 0.007, P = 0.0111). Moreover, their levels also accurately reflected the pseudoprogression of two NSCLC patients to anti-PD-1 treatment. CONCLUSIONS: Our results suggested that serum IL-5 and IFN-γ levels could be an effective indicator for predicting clinical efficacy and survival with anti-PD-1 blockade in NSCLC and GC patients.

Cholinesterase is Associated With Prognosis and Response to Chemotherapy in Advanced Gastric Cancer.

Background: Cholinesterase (CHE) is a routine serum biomarker in gastric cancer (GC). However, little research has been done on its clinical value in advanced GC. In addition, it is not clear whether it can be used as biomarker for the response and prognosis of advanced GC patients. Methods: Between Jan. 2013 and Dec. 2016, a total of 150 patients with advanced GC treated with first-line chemotherapy were admitted to Changzhou Tumor Hospital Affiliated to Soochow University. We retrospectively identified serum CHE level on the day before chemotherapy and at the end of chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between serum CHE levels and progression-free survival (PFS) and overall survival (OS). Results: A total of 150 advanced GC patients were included and divided into serum level ≥5,000 IU/L and serum level <5,000 IU/L. CHE level lower than 5,000 IU/L was associated with poorer PFS (HR, 1.60; 95% CI, 1.141-2.243; p = 0.006), poorer OS (HR, 1.76; 95% CI, 1.228-2.515; p = 0.002) and trend of poorer response (HR, 0.56; 95% CI, 0.272-1.129; p = 0.104). In univariate and multivariate logistic regression analysis, only liver metastasis and PS score were significantly associated with objective response (p < 0.05). The medium PFS was 8.0 months in patients with post-treatment CHE increased vs. 3.8 months in patients with CHE decreased after chemotherapy (HR, 1.82; 95% CI 1.28-2.57; p = 0.0002). The medium OS was 13.1 months in patients with increased post-treatment CHE vs. 8.1 months in patients with decreased post-treatment CHE (HR, 1.87; 95% CI 1.29-2.71; p = 0.0002). Conclusion: Advanced GC with CHE levels below 5,000 IU/L was significantly associated with poor PFS and OS. The results suggested that CHE analysis before chemotherapy was a promising prognostic marker for advanced GC.

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study.

Previous coronavirus pandemics were associated elevated post-traumatic stress symptoms (PTSS), but the self-report and neurological basis of PTSS in patients who survived coronavirus disease 2019 (COVID-19) are largely unknown. We conducted a two-session study to record PTSS in the COVID-19 survivors discharged from hospitals for a short (i.e., about 3 months, Session 1) to a medium period (i.e., about 6 months, Session 2), as well as brain imaging data in Session 2. The control groups were non-COVID-19 locals. Session 1 was completed for 126 COVID-19 survivors and 126 controls. Session 2 was completed for 47 COVID-19 survivors and 43 controls. The total score of post-traumatic stress disorder (PTSD) checklist for DSM-5 (PCL-5) score was significantly higher in COVID-19 survivors compared with controls in both sessions. The PCL-5 score in COVID-19 survivors was positively correlated with the duration after discharge (r = 0.27, p = 0.003 for Session 1), and increased by 20% from Session 1 to Session 2 for the survivors who participated both sessions. The increase was positively correlated with individual's test-retest duration (r = 0.46, p = 0.03). Brain structural volume and functional activity in bilateral hippocampus and amygdala were significantly larger in COVID-19 survivors compared with controls. However, the volumes of the left hippocampus and amygdala were negatively correlated with the PCL-5 score for the COVID-19 survivors. Our study suggests that COVID-19 survivors might face possible PTSS deteriorations, and highlights the importance of monitoring mental wellness of COVID-19 survivors.

A modality selective effect of functional laterality in pain detection sensitivity.

The ability to detect environmental changes is essential to determine the appropriate reaction when facing potential threats. Both detection and reaction functions are critical to survival, and the superior performance of motor reaction for the dominant hand is well recognized in humans. However, it is not clear whether there exists laterality in sensitivity to detect external changes and whether the possible laterality is associated with sensory modality and stimulus intensity. Here, we tested whether the perceptual sensitivity and electrophysiological responses elicited by graded sensory stimuli (i.e., nociceptive somatosensory, non-nociceptive somatosensory, auditory, and visual) that were delivered on/near the left and right hands would be different for right-handed individuals. We observed that perceived intensities and most brain responses were significantly larger when nociceptive stimuli were delivered to the left side (i.e., the non-dominant hand) than to the right side (i.e., the dominant hand). No significant difference was observed between the two sides for other modalities. The higher sensitivity to detect nociceptive stimuli for the non-dominant hand would be important to provide a prompt reaction to noxious events, thus compensating for its worse motor performance. This laterality phenomenon should be considered when designing experiments for pain laboratory studies and evaluating regional sensory abnormalities for pain patients.

Test-retest reliability of laser evoked pain perception and fMRI BOLD responses.

Pain perception is a subjective experience and highly variable across time. Brain responses evoked by nociceptive stimuli are highly associated with pain perception and also showed considerable variability. To date, the test-retest reliability of laser-evoked pain perception and its associated brain responses across sessions remain unclear. Here, an experiment with a within-subject repeated-measures design was performed in 22 healthy volunteers. Radiant-heat laser stimuli were delivered on subjects' left-hand dorsum in two sessions separated by 1-5 days. We observed that laser-evoked pain perception was significantly declined across sessions, coupled with decreased brain responses in the bilateral primary somatosensory cortex (S1), right primary motor cortex, supplementary motor area, and middle cingulate cortex. Intraclass correlation coefficients between the two sessions showed "fair" to "moderate" test-retest reliability for pain perception and brain responses. Additionally, we observed lower resting-state brain activity in the right S1 and lower resting-state functional connectivity between right S1 and dorsolateral prefrontal cortex in the second session than the first session. Altogether, being possibly influenced by changes of baseline mental state, laser-evoked pain perception and brain responses showed considerable across-session variability. This phenomenon should be considered when designing experiments for laboratory studies and evaluating pain abnormalities in clinical practice.