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People as third-party observers, without direct self-interest, may punish norm violators to maintain social norms. However, third-party judgment and the follow-up punishment might be susceptible to the way we frame (i.e., verbally describe) a norm violation. We conducted a behavioral and a neuroimaging experiment to investigate the above phenomenon, which we call the “third-party framing effect”. In these experiments, participants observed an anonymous perpetrator deciding whether to keep her/his economic benefit while exposing a victim to a risk of physical pain (described as “harming others” in one condition and “not helping others” in the other condition), then they had a chance to punish that perpetrator at their own cost. Our results showed that the participants were more willing to execute third-party punishment under the harm frame compared to the help frame, manifesting a framing effect. Self-reported anger toward perpetrators mediated the relationship between empathy toward victims and the framing effect. Meanwhile, activation of the insula mediated the relationship between mid-cingulate cortex activation and the framing effect; the functional connectivity between these regions significantly predicted the size of the framing effect. These findings shed light on the psychological and neural mechanisms of the third-party framing effect.

Guozhong Ma,1 Liuqing Sun,2 Zhiwei Qie,3 Jinzhao He,1 Fang Cui2 1Department of Neurology, Heyuan People’s Hospital, Heyuan, Guangdong Province, 517000, People’s Republic of China; 2Department of Neurology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Sanya, Hainan Province, 572013, People’s Republic of China; 3Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of ChinaCorrespondence: Guozhong MaDepartment of Neurology, Heyuan People’s Hospital, No. 733 Wenxiang Road, Yuancheng District, Heyuan, Guangdong Province, 517000, People’s Republic of ChinaTel/Fax +86-0762-3185571Email guozhong-ma@hotmail.comFang CuiDepartment of Neurology, Hainan Hospital of Chinese People’s Liberation Army General Hospital, Haitang District, Sanya, Hainan Province, 572013, People’s Republic of ChinaTel/Fax +86- 0898-37330625Email cuifanghaitang@hotmail.comPurpose: To investigate the prevalence of short- and long-term benzodiazepine and z-drugs (BZD) for the treatment of post-stroke subjective sleep disturbance (SSD) and to evaluate the risk factors associated with prolonged BZD treatment in this patient body.Patients and Methods: Between 1st January 2018 and 1st December 2018, we identified 542 inpatients suffering from acute stroke in Heyuan People’s Hospital. Of these, 290 inpatients were included in our final analysis. These patients were divided into three groups according to the treatment they received: non/occasional BZD (non-BZD), short-term BZD (short-term) and prolonged-term BZD (prolonged-term) treatment. We investigated the prevalence of each BZD treatment term and identified differences between the groups. Univariate logistic regression analysis was used to identify potential predictors for the prolonged use of BZD. Multinomial logistic regression analysis was used to assess the correlation between the prolonged use of BZD and potential predictors.Results: The prevalence of cases receiving short and prolonged BZD treatments were 40.35% and 31.72%, respectively; none of the patients received polysomnography (PSG) screening from obstructive sleep apnoea (OSP). Treatment strategies were limited to BZD and traditional Chinese medicine; none of the patients received cognitive-behavioral treatment (CBT) or other forms of treatment. Logistic regression analysis showed that the short-term use was associated with z-drugs (odds ratio [OR]: 2.189, 95% confidence interval [CI]: 1.419– 3.378), non-communication barriers (OR =0.535, 95% CI: 0.325– 0.880) and posterior circulation infarct (POCI) (OR =2.199, 95% CI: 1.112– 4.349). The prolonged-term use was associated with z-drugs (OR =3.012, 95% CI: 1.637– 5.542), non-communication barriers (OR =0.530, 95% CI: 0.307– 0.916), partial anterior circulation infarct (PACI) (OR =0.455, 95% CI: 0.250– 0.827), and non pain after stroke (OR =0.315, 95% CI: 0.207– 0.480).Conclusion: The status of BZD abuse for post-stroke SSD is worrying. Additional research attention and treatment options are needed for the treatment of post-stroke SSD. In particular, the potential combination of stroke and OSP appears to be underestimated and neglected. Post-stroke SSD patients should receive more comprehensive assessment and rigid follow-up to avoid the prolonged use of BZD. Additional and effective therapeutic strategies (such as positive pressure ventilation treatment or CBT) are urgently needed for cause-specific intervention.Keywords: benzodiazepine and z-drugs, BZD, prolonged-use, post-stroke, subjective sleep disturbance, SSD, risk factors, obstructive sleep apnea, OSP, China

Sex differences in various aspects of behaviour and cognition have been widely observed. Few studies, however, have explored potential sex differences in maintaining a balanced time perspective or their underlying neural correlates. To address these questions, two studies were conducted. In Study 1, time perspective was assessed in 1913 college students (796 males and 1117 females), revealing that females had a significantly more balanced time perspective relative to males. In Study 2, 58 males and 47 females underwent an assessment of time perspective and structural brain imaging. Voxel-based morphometry analysis and cortical thickness analysis were conducted to explore associations between the structural imaging data and balanced time perspective. Compared with males, females demonstrated a more balanced time perspective in the context of lower grey matter volume in the bilateral precuneus, right cerebellum, right putamen and left supplementary motor area. Analysis of cortical thickness failed to reveal any significant sex differences. Furthermore, lower grey matter volume of bilateral precuneus was associated with more balanced time perspective among all participants. Our findings point to a critical role for the precuneus in modulating a balanced time perspective, and extend our understanding of sex differences in human cognition. Future studies are required to determine whether sex differences in balanced time perspective are predictive of functional outcomes in daily life.

Patients with schizophrenia (SCZ) consistently show prospective memory (PM) impairments, and the technique of implementation intentions has been shown to improve PM performance in these patients. PM is considered to have prospective and retrospective components. However, it remains unclear which component of PM is impaired in patients with SCZ and which component(s) is facilitated by implementation intentions (II). The present study aimed to examine these two issues. Forty-two patients with SCZ and 42 matched healthy controls were randomly assigned to an II group or a typical instruction group. All participants were administered a color-matching PM task. Results showed that, using a multinomial-modeling approach, patients with SCZ exhibited impairment in the retrospective component of PM. In addition, while II improved the prospective PM component in healthy controls, both prospective and retrospective PM components in patients with SCZ were improved. Together, our results shed light on the mechanism of PM impairment in SCZ patients and the mechanism of II in improving PM performance.

Rationale: Malignant ascites caused by cancer cells results in poor prognosis and short average survival time. No effective treatment is currently available for malignant ascites. In this study, the effects of lentinan (LNT)-functionalized selenium nanoparticles (Selene) on malignant ascites were evaluated. Furthermore, the mechanism of Selene targeting mitochondria of tumor cells were also investigated. Methods: Selene were synthesized and characterized by TEM, AFM and particle size analysis. The OVCAR-3 and EAC cells induced ascites models were used to evaluate the effects of Selene on malignant ascites. Proteomic analysis, immunofluorescence, TEM and ICP-MS were used to determine the location of Selene in tumor cells. Mitochondrial membrane potential, ROS, ATP content, and caspase-1/3 activity were detected to evaluate the effect of Selene on mitochondrial function and cell apoptosis. Immunofluorescence, Co-IP, pull-down, duolink, Western blot, and FPLC were used to investigate the pathway of Selene targeting mitochondria. Results: Selene could effectively inhibit ascites induced by OVCAR-3 and EAC cells. Selene was mainly located in the mitochondria of tumor cells and induced apoptosis of tumor cells. The LNT in Selene was involved in caveolae-mediated endocytosis through the interaction between toll-like receptor-4 (TLR4) and caveolin 1 (CAV1). Furthermore, the Selene in the endocytic vesicles could enter the mitochondria via the mitochondrial membrane fusion pathway, which was mediated by TLR4/TNF receptor associated factor 3 (TRAF3)/mitofusin-1 (MFN1) protein complex. Conclusion: Selene is a candidate anticancer drug for the treatment of malignant ascites. And TLR4/TRAF3/MFN1 may be a specific nano-drug delivery pathway that could target the mitochondria.

Background A previous study by our team reported the prevalence of primary headache disorders and factors associated with headache among nurses in three hospitals in North China. The aim of this cross-sectional survey was to learn more about how medical nurses in South China were affected by headache. Additionally, we determined the prevalence of headache and measured the impact of headache among doctors in mainland China for the first time. Methods Stratified random cluster sampling was used to select 280 physicians and 365 nurses from various departments in four hospitals in Sanya, which is one of southernmost cities in China. Information was collected on demographic data, occupational factors and headache characteristics by using a structured questionnaire. Results Among 645 medical staff, 548 (85%) responded (doctors = 240, nurses = 308). Among the medical staff, the 1-year prevalence of primary headache disorders was 50%, with 25.9% experiencing migraine and 24.1% experiencing tension-type headache (TTH). The prevalence of migraine in female doctors was higher than that in female nurses, although this difference was not significant (32.4% vs. 29.8%, P = 0.628). Multivariate analysis showed that being female and working in other specialties (Emergency Department & Radiology Department) remained independent risk factors for migraine in doctors (OR 2.314 and 3.223). In nurses, being married was a risk factor for migraine (OR 3.728), and job titles remained an independent risk factor for migraine and TTH (OR 2.294 and 4.695). Working more than 6 night-shifts per month was associated with an increased prevalence of migraine and TTH in doctors; the same was true in nurses for migraine, but not for TTH. Conclusion The prevalence of primary headache disorders in both nurses and doctors is higher than that in the general population in South China. Our study shows that occupation, geography and sex may play an important role. Further, female doctors are more susceptible than female nurses to migraine. The risk factors relevant to headache that were found in this study should provide an important reference for promoting occupational health in medical staff, especially female doctors in China.

Involuntary mental time travel (MTT) refers to the phenomenon of mentally reliving past experiences or pre-living possible future events in an involuntary form. Few studies have explored involuntary MTT in individuals with schizotypal personality features. The present study aimed to first explore the psychometric properties of the Involuntary Autobiographic Memory Inventory (IAMI) in a Chinese sample (Study 1), and then to explore whether individuals with schizotypal personality features experience involuntary MTT more frequently than individuals without schizotypal features. Moreover, the study explored whether the aberrant frequency of involuntary MTT is correlated with positive schizotypal features (Study 2). The results showed that the IAMI had good structural validity and reliability in a Chinese sample. Individuals with schizotypal traits reported a significantly higher frequency, less positive emotion, and stronger emotional intensity for both involuntary memories and future thoughts compared with individuals without schizotypal features. Further analyses in individuals with schizotypal personality features showed that the frequencies of both involuntary memories and future thoughts were significantly correlated with positive schizotypal traits. These results have potential theoretical and clinical implications for a comprehensive understanding of involuntary MTT among individuals with schizotypal personality features.

Cystic echinococcosis (CE), a zoonotic disease caused by Echinococcus granulosus at the larval stage, predominantly develops in the liver and lungs of intermediate hosts and eventually results in organ malfunction or even death. The interaction between E. granulosus and human body is incompletely understood. Exosomes are nanosized particles ubiquitously present in human body fluids. Exosomes carry biomolecules that facilitate communication between cells. To the best of our knowledge, the role of exosomes in patients with CE is not reported. Here, we isolated exosomes from the sera of patients with CE (CE-exo) and healthy donors and subjected them to liquid chromatography-tandem mass spectrometry analysis. Proteomic analysis identified 49 proteins specifically expressed in CE-exo, including 4 proteins of parasitic origin. The most valuable parasitic proteins included tubulin alpha-1C chain and histone H4. And 8 proteins were differentially regulated in CE-exo (fold changegt;1.5), as analyzed with bioinformatic methods such as annotation and functional enrichment analyses. These findings may improve our understanding about the interaction between E. granulosus and human body, and may contribute to the diagnosis and prevention of CE.

Previous behavioral studies have shown that sharing painful experiences can strengthen social bonds and promote mutual prosociality, yet the neural mechanisms underlying this phenomenon remain unclear. We hypothesized that sharing a painful experience induces brain-to-brain synchronization and mutual empathy for each other's pain between pain-takers and pain-observers, which then leads to enhanced social bonding. To test this hypothesis, we adopted an electroencephalographic (EEG) hyper-scanning technique to assess neuronal and behavioral activity during a Pain-Sharing task in which high- or low-intensity pain stimulation was randomly delivered to one participant of a dyad on different experimental trials. Single-brain analysis showed that sensorimotor α-oscillation power was suppressed more when expecting high-intensity pain than when expecting low-intensity pain similarly for self-directed or partner-directed pain. Dual-brain analysis revealed that expecting high-intensity pain induced greater brain-to-brain synchronization of sensorimotor α-oscillation phases between pain-takers and pain-observers than did expecting low-intensity pain. Mediation analysis further revealed that brain-to-brain synchronization of sensorimotor α-oscillations mediated the effects of pain-stimulation intensity on mutual affective sharing for partner-directed pain. This mutual affective empathy during the task predicted the social bonding, as indexed by prosocial inclinations measured after the task. These results support the hypothesis that sharing a painful experience triggers emotional resonance between pairs of individuals through brain-to-brain synchronization of neuronal α-oscillations recorded over the sensorimotor cortex, and this emotional resonance further strengthens social bonds and motivates prosocial behavior within pairs of individuals.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Spreading pattern and time interval of spreading are getting more and more attention. The aim of present study was to investigate spreading pattern in bulbar onset ALS patients and to explore the relationship between time interval of spreading and survival.ALS patients with bulbar onset diagnosed at Chinese PLA General Hospital from January 2015 to December 2018 were recruited. Clinical features including gender, onset age, diagnostic delay, the second involved region (SIR), time of symptoms beyond the bulbar region, forced vital capacity (FVC), ALSFRS-R score, electromyography results, and survival time were retrospectively collected.A total of 96 bulbar onset ALS patients were collected. Overall patients showed female predominance. Median age at onset was 56 years. Median diagnostic delay was 8.5 months. Median time of symptoms beyond the bulbar region (TBBR) was 7 months. Median ALSFRS-R score at baseline was 40. Fifty-six (58.3%) patients' SIR were upper limb, 6 (6.3%) patients' SIR were lower limb, 3 (3.1%) patients' SIR were upper and lower limbs, and 5 (5.2%) patients' SIR were thoracic region. Twenty-six (27.1%) patients did not report SIR. The median survival time of patients with TBBR ≥ 7 months was significantly longer than that with TBBR 7 month. Multivariate Cox regression showed that onset age and TBBR were prognostic factors.In bulbar onset ALS patients, cervical region is the second most common SIR. TBBR is an independent prognostic factor.

Schizotypy, a subclinical group at risk for schizophrenia, has been found to show impairments in response inhibition. However, it remains unclear whether this impairment is accompanied by outright stopping (reactive inhibition) or preparation for stopping (proactive inhibition). We recruited 20 schizotypy and 24 non-schizotypy individuals to perform a modified stop-signal task with electroencephalographic (EEG) data recorded. This task consists of three conditions based on the probability of stop signal: 0% (no stop trials, only go trials), 17% (17% stop trials), and 33% (33% stop trials), the conditions were indicated by the colour of go stimuli. For proactive inhibition (go trials), individuals with schizotypy exhibited significantly lesser increase in go response time (RT) as the stop signal probability increasing compared to non-schizotypy individuals. Individuals with schizotypy also exhibited significantly increased N1 amplitude on all levels of stop signal probability and increased P3 amplitude in the 17% stop condition compared with non-schizotypy individuals. For reactive inhibition (stop trials), individuals with schizotypy exhibited significantly longer stop signal reaction time (SSRT) in both 17% and 33% stop conditions and smaller N2 amplitude on stop trials in the 17% stop condition than non-schizotypy individuals. These findings suggest that individuals with schizotypy were impaired in both proactive and reactive response inhibition at behavioural and neural levels.

The person-centered account of moral judgments is important since immoral behaviors are diagnostic of an individual’s character. The present study explored how the professional stereotypes associated with the agents shaped the way people perceiving moral/immoral behaviors. The behavioral ratings and neural responses (i.e., P200, N2, LPC event-related potentials (ERPs)) to moral/immoral behaviors done by agents with respectable or ordinary professional roles were recorded and compared. Behaviorally, we found that participants rated the agent with a respectable professional role behaving immorally as more dislikable comparing to the agent with an ordinary professional role. For ERPs, we found that: 1) the agents with respectable professional roles elicited larger P200 than agents with ordinary professional roles did; 2) immoral behavior elicited larger LPC than moral behaviors did; 3) for agents with respectable professional roles, the immoral behaviors elicited significantly more positive N2 than the moral behaviors did whereas this difference was not significant for the agents with ordinary professional roles. The immoral behaviors done by agents with respectable professional roles elicited more positive N2 than the immoral behavior done by agents with ordinary professional roles. Moreover, this effect was correlated with the participants’ subjective rating of the professional roles’ respectable level. These results suggest that 1) the more the agents with respectable professional roles are respected, the more dislikable they became when behaving immorally; 2) the moral stereotype associated with professional roles can influence the early processing stage reflected in N2 but not the later evaluative process reflected in LPC.

An individual's economic valuation of a given object is biased by the moral status of the persons to whom the object is attached. The neural basis for how such "moral bias" occurs, especially how it is maintained in the resting state, are largely unknown. In the current study, we explored this question by correlating the functional connectivity with participants' behavioral performance measured in a novel task which captured how the economic valuation was influenced by given moral information. Seed-based FC analysis showed that the functional connectivity between the mPFC and the orbital mPFC (omPFC), the mPFC and the precuneus, the mPFC and the left anterior cingulum, were significantly associated with the behavioral index of morality effect on economic valuation. Multivariate machine learning-based regression analysis showed that connections in the mPFC network, as well as in the putamen network could well predict the behavior performance, indicating that this mPFC network and the putamen network were crucial for this moral bias. Our results further revealed that the individuals' personal trait of moral sensitivity served as a mediator between the rsFC of mPFC network and the behavioral index of morality effect on economic valuation.

Predictability has been suggested to modulate both the anticipation and perception of self-pain. Considering the overlapping neural circuits between self-pain and other-pain perceptions, the present study investigated how the predictability of forthcoming pain modulates the anticipation and perception of self-pain and other-pain. We used a balanced, within-participant experimental design in which a visual cue indicating the recipient, intensity and predictability of an upcoming painful electrical stimulation was presented before its delivery. Subjective ratings and electroencephalography activities to the anticipation and perception of self-pain and other-pain were recorded and compared between certain and uncertain conditions. Results showed that predictability affected the perception of self-pain and other-pain in a similar manner such that the differences in behavioral ratings and event-related potentials to high-intensity and low-intensity pain were significantly reduced when the intensity was uncertain. The strengths of predictability-induced modulation of self-pain and other-pain perceptions were positively correlated with each other. Furthermore, predictability also modulated the anticipation of both self-pain and other-pain such that pre-stimulus high-frequency α-oscillation power at sensorimotor electrodes contralateral to the stimulation side was maximally suppressed when anticipating certain high-intensity pain. These findings demonstrate that predictability-induced modulation on pain anticipation and perception was similarly applied to both self-pain and other-pain.

Background: It is important to determine prognostic factors for the outcome of amyotrophic lateral sclerosis (ALS) at an early stage. The time taken for symptoms to spread from spinal or bulbar regions to both (time to generalization; TTG) is considered a strong predictor of survival; however, this has rarely been studied in Asian populations. The aim of this retrospective study was to evaluate potential factors affecting prognosis in Chinese patients with sporadic ALS, with a focus on the association between TTG and overall survival. Methods: Seventy-one patients with sporadic ALS who were hospitalized at Chinese PLA General Hospital from 2009 to 2016 were followed up until December 2017. Survival analysis was performed using univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards models. The clinical data of the patients were recorded and analyzed. Variables studied were age at symptom onset, sex, site of symptom onset, diagnostic latency, TTG, diagnostic category, ALS Functional Rating Scale-revised score, percent predicted forced vital capacity (FVC%), and disease progression rate (DPR) at diagnosis. Results: The mean age at onset was 54 (SD = 10.2) years, and the median survival time from symptom onset was 41 months (95% confidence interval: 34–47). By univariate analysis, factors independently affecting survival were age at symptom onset (Log rank = 15.652, P < 0.0001), TTG (Log rank = 14.728, P < 0.0001), diagnostic latency (Log rank = 11.997, P = 0.001), and DPR (Log rank = 6.50, P = 0.011). In the Cox multivariate model, TTG had the strongest impact on survival time (hazard ratio = 0.926, P = 0.01). Conclusions: TTG can be used as an effective indicator of prognosis in patients with sporadic ALS. Key words: Amyotrophic lateral sclerosis; Time to generalisation (TTG); Prognosis; Survival

The beneficial effect of implementation intentions (II) on prospective memory (PM) deficits in patients with schizophrenia has been reported. However, these studies were limited to brief interventions such that the transfer and long-term effects of II training remains unclear. This study examined whether a 10-session II programme could improve PM performance, social functioning and functional capacity in patients with schizophrenia immediately after training and at 3-month follow-up. Patients with schizophrenia (n = 42) recruited from the community were randomly assigned to II training (n = 21) or treatment as usual (TAU) (n = 21). Participants in the II group learned the verbal and imagery component of II and were encouraged to apply these strategies in their daily lives. We found that the II group performed better than the TAU group on computer-based PM tasks and a daily life PM task (telephone call at specified date and time) at post-treatment and at 3-month follow-up. The II group also exhibited better working ability than the TAU group at post-treatment. Our results suggest that the II intervention programme may have lasting beneficial effects in PM performance and significant transfer effects to functional capacity in schizophrenia patients.

Objective: The objective of this study was to compare iron metabolic variables in the serum and cerebrospinal fluid (CSF) of patients with sporadic amyotrophic lateral sclerosis (sALS) with those o...

Moral contagion is a phenomenon in which individuals or objects take on the moral essence of the people who are associated with them. Previous studies have found that individuals value objects associated with moral and likable people more than those associated with immoral and dislikable people. However, the neural mechanisms underlying this "moral contagion effect" have not yet been explored. In the present study, we combined a novel "Second-hand Goods Pricing" paradigm with functional magnetic resonance imaging to (a) confirm the existence of the moral contagion effect on the hypothetical economic valuation of objects and (b) determine the neural substrates underlying it. Participants were shown second-hand goods, information regarding the moral valence of the previous owner, and an initial price assigned to the object by computer. The participants were then asked to adjust the initial price to one they deemed most reasonable. Behaviorally, we found a significant devaluation effect for immoral owners and a weaker reverse effect for moral owners. Imaging data showed that the devaluation effect was primarily driven by neural responses in the dorsal striatum (mainly the caudate nucleus) that were triggered by high initial prices assigned to the "contaminated" objects. Dynamic causal modeling revealed that the high initial price assigned to "contaminated" objects led to increased effective connectivity from the caudate nucleus to the ventromedial prefrontal cortex-the brain area that integrates values during decision making.

Mutations in the SH3TC2 gene cause Charcot-Marie-Tooth disease type 4C (CMT4C), characterized by inherited demyelinating peripheral neuropathy. CMT4C is a common form of CMT4/autosomal recessive (AR) CMT1. This study examined the SH3TC2 variants, investigated genotype-phenotype correlations and explored the frequency of CMT4C in Chinese patients. A total of 206 unrelated patients of Chinese Han descent clinically diagnosed with CMT were recruited. All patients underwent detailed history-taking, neurological examination, laboratory workups, and electrophysiological studies. Genetic analysis was performed via high-throughput target sequencing (NGS). Three patients, one male and two females, were found to carry five SH3TC2 mutations: patient 1 (c.3154C T, p.R1054X; c.929G A, p.G310E); Patient 2 (c.2872_2872del, p.S958fs; c.3710C T, p.A1237V) and Patient 3 (c.2782C T, p.Q928X; c.929G A, p.G310E). The c.2872_2872del, c.3710C T and c.2782C T variants were not reported before. CMT4C caused by SH3TC2 mutation is a very common type of CMT4/AR CMT1. Three novel mutations, c.2872_2872del, c.3710C T and c.2782C T, were found in this study. Combination of clinical phenotype, nerve conduction studies, genetic analysis and bioinformatics analysis are of vital importance in patients suspected as CMT.

As an important cognitive bias, the framing effect shows that our decision preferences are sensitive to the verbal description (i.e., frame) of options. This study focuses on the neural underpinnings of the social framing effect, which is based on decision-making regarding other people. A novel paradigm was used in which participants made a trade-off between economic benefits and the feelings of others. This decision was described as either a “harm” to, or “not helping,” other persons in two conditions (Harm frame vs Help frame). Both human males and females were recruited. Participants behaved more prosocially for Harm frame compared with Help frame, resulting in a significant social framing effect. Using functional magnetic resonance imaging, Experiment 1 showed that the social framing effect was associated with stronger activation in the temporoparietal junction (TPJ), especially its right part. The functional connectivity between the right TPJ (rTPJ) and medial prefrontal cortex predicted the social framing effect on the group level. In Experiment 2, we used transcranial direct current stimulation to modulate the activity of the rTPJ and found that the social framing effect became more prominent under anodal (excitatory) stimulation, while the nonsocial framing effect elicited by the economic gain/loss gambling frame remained unaffected. The rTPJ results might be associated with moral conflicts modulated by the social consequences of an action or different levels of mentalizing with others under different frame conditions, but alternative interpretations are also worth noting. These findings could help elucidate the psychological mechanisms of the social framing effect.SIGNIFICANCE STATEMENTPrevious studies have suggested that the framing effect is generated from an interaction between the amygdala and anterior cingulate cortex. This opinion, however, is based on findings from nonsocial framing tasks. Recent research has highlighted the importance of distinguishing between the social and nonsocial framing effects. The current study focuses on the social framing effect and finds out that the temporoparietal junction and its functional connectivity with the medial prefrontal cortex play a significant role. Additionally, modulating the activity of this region leads to changes in social (but not nonsocial) framing effect. Broadly speaking, these findings help understand the difference in neural mechanisms between social and nonsocial decision-making. Meanwhile, they might be illuminating to promote helping behavior in society.

The present study investigates how agents and the moral valence of the acts affect moral judgments when two consecutively behaviors are perceived, with each describing morally salient behaviors done by the same or different agent(s). Participants had to rate the likableness/pleasantness of the agents/behaviors. Behavioral results indicated that rating the likableness of the agent was mainly depended on the morally diagnostic character of the agent while rating the pleasantness of the behaviors was mainly depended on the moral valence of the behaviors per se. ERP results showed: 1) larger N1 was found in response to the agent consistently acting immorally, indicating an early detection of social threatening information. 2) Compared with agents who consistently act morally which provided no norm- or expectation-violation information, other conditions induced larger N400, indicating greater cognitive effort was recruited when the present moral information violated the participants' prior knowledge to the agent. 3) Increased LPP was found in response to the agent consistently acting morally (vs. moral behaviors acted by different agents), representing that people may allocate more attention to positive information during this stage. We suggest that this three-stage scheme is a common model when people encounter consecutive moral events.

Background: Whether occupation has an impact on contact heat evoked potential (CHEP) results has not been investigated. In this study, we investigated the difference of CHEP parameters between knowledge workers and unskilled labors. Methods: A total of 137 healthy participants were recruited between November 20, 2014 and December 31, 2016. All participants underwent neurologic examination, laboratory examination, and nerve conduction studies. CHEP was performed on four body sites: the upper border of the distal third of the volar forearm, the upper border of the distal third of the lateral leg, the spinous process of seventh cervical vertebrae (C7), and the spinous process of 12th thoracic vertebrae (T12). Independent t test and nonparametric test were performed using SPSS software to compare the difference of the CHEP parameters between knowledge workers and unskilled labors. Results: The "N2 latency/height" (Z = -2.290, P = 0.022) and "P2 latency/height" (Z = -2.020, P = 0.043) on the volar forearm of unskilled labors significantly increased than those of knowledge workers. The "N2 latency/height" (F = 6.348, P = 0.016) and "P2 latency/height" (F = 5.920, P = 0.018) in the distal leg of unskilled labors significantly prolonged than those of knowledge workers. The N2-P2 amplitude (F = 5.797, P = 0.020) in the distal leg of unskilled labors significantly decreased than those of knowledge workers. Conclusions: Our study found that significantly prolonged N2 latency and P2 latency and significantly decreased N2-P2 amplitude in the distal leg and the volar forearm in unskilled labors as to knowledge workers. Key words: Contact heat evoked potential; Occupation; Nerve conduction studies

Spinal cord injury (SCI) often results in permanent functional loss due to a series of degenerative events including cell death, axonal damage, and the upregulation of inhibitory proteins that impede regeneration. Repulsive Guidance Molecule A (RGMa) is a potent inhibitor of axonal growth that is rapidly upregulated following injury in both the rodent and human central nervous system (CNS). Previously, we showed that monoclonal antibodies that specifically block inhibitory RGMa signaling promote neuroprotective and regenerative effects when administered acutely in a clinically relevant rat model of thoracic SCI. However, it is unknown whether systemic administration of RGMa blocking antibodies are effective for SCI after delayed administration. Here, we administered elezanumab, a human monoclonal antibody targeting RGMa, intravenously either acutely or at 3 h or 24 h following thoracic clip impact-compression SCI. Rats treated with elezanumab acutely and at 3 h post-injury showed improvements in overground locomotion and fine motor function and gait. Rats treated 24 h post-SCI trended towards better recovery demonstrating significantly greater stride length and swing speed. Treated rats also showed greater tissue preservation with reduced lesion areas. As seen with acute treatment, delayed administration of elezanumab at 3 h post-SCI also increased perilesional neuronal sparing and serotonergic and corticospinal axonal plasticity. In addition, all elezanumab treated rats showed earlier spontaneous voiding ability and less post-trauma bladder wall hypertrophy. Together, our data demonstrate the therapeutic efficacy of delayed systemic administration of elezanumab in a rat model of SCI, and uncovers a new role for RGMa inhibition in bladder recovery following SCI.

Objectives Interleukin-37 (IL-37) has been identified as a potent inhibitor of the immune response. This study aimed to examine IL-37 expression in patients with chronic active hepatitis B (CAHB), and explore its possible regulatory role during inflammation. Methods Peripheral blood mononuclear cells (PBMCs) were collected from control (n = 20) and CAHB patients (n = 30) before and after treatment with entecavir (EVT) for 24 weeks. The PBMCs were cultured with lipopolysaccharide and IL-37 expression was determined by real-time polymerase chain reaction and flow cytometry. The mRNA and protein concentrations of IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in PBMCs were also measured. Results Levels of IL-37, IL-1β, IL-6, and TNF-α were significantly increased in the supernatant of PBMCs from patients with CAHB. IL-37 significantly reduced the expression of IL-1β, IL-6, and TNF-α. EVT resulted in regression of intraocular inflammation in patients with CAHB, associated with decreased production of IL-37. Conclusion These results suggest that increased expression of IL-37 was associated with the suppression of the inflammatory response in patients with CAHB. Furthermore, EVT treatment of CAHB was also correlated with downregulation of IL-37, indicating that EVT may partially alleviate the immune response by modulating IL-37 production.

The effect of leptin on ulcerative colitis (UC) has been controversial. The present study aimed to investigate the role of leptin and its receptor ob‑R in UC and the underlying mechanism of this role. The level of serum leptin and the protein expression of the leptin receptor ob‑R in the colonic mucosa were determined in patients with UC. Experimental colitis was induced through intrarectal administration of 2,4,6‑trinitrobenzene sulfonic acid (TNBS) in leptin receptor‑deficient Zucker rats (LR‑D). The body weight, disease activity index, colon length, and macroscopic and histopathological appearance were evaluated. Furthermore, the myeloperoxidase (MPO) enzyme activity and cytokine levels in colon tissues were also determined. The expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 (p‑STAT3), nuclear factor (NF)‑κB‑p65, and Ras homolog gene family member A (RhoA) proteins in colon tissues was assessed. The results revealed that the expression of the leptin receptor ob‑R was increased in the colonic mucosa but the serum leptin level was not altered in patients with UC compared with healthy volunteers. The severity of experimental colitis, represented by body weight loss, disease activity index, colon length, and macroscopic and histological changes, was ameliorated in LR‑D rats compared with the wild‑type (WT) rats. Moreover, the MPO activity; levels of cytokines including interleukin (IL)‑1β, IL‑6, and tumor necrosis factor‑α; and expression of p‑STAT3, NF‑κB, and RhoA proteins were reduced in colon tissues of LR‑D rats compared with WT rats. In conclusion, activation of the leptin receptor ob‑R is an important pathogenic mechanism of UC, and leptin receptor deficiency may provide resistance against TNBS‑induced colitis by inhibiting the NF‑κB and RhoA signaling pathways.

Mental Time Travel (MTT) is the ability of individuals to project themselves to the past or to the future. Studies have shown that schizophrenia (SZ) patients are impaired in MTT. The present study aimed to examine whether MTT in patients with SZ can be improved through Life Review Therapy. Fifty patients with SZ were randomly assigned to the training (SZ-training) or control (SZ-control) group. Whereas the SZ-training group received four-week Life Review Therapy in addition to conventional treatment, the SZ-control group only received conventional treatment. MTT, emotional status, life satisfaction and cognitive functions were assessed before and after the training. We also recruited 25 matched healthy controls to complete all the assessments at baseline. After training, the SZ-training group showed higher specificity and more field perspective than the SZ-control group. No significant difference was found between the SZ-training group post-training assessment and the healthy controls. The SZ-training group also showed significant improvements in emotional expression, semantic memory and verbal fluency, but the SZ-control group did not show such improvements. These results indicated that Life Review Therapy is effective in improving MTT of SZ patients.

People tell lies not only for their own self-interests but sometimes also to help others. Little is known about the ways in which different types of goals modulate behaviors and neural responses in deception. The present study investigated the neural processes associated with spontaneous deception that occurs with altruistic reasons (i.e. the money would be donated to charity), self-serving reasons (i.e. the participant receives all of the money) and mixed goals (i.e. the money would be equally split between the participant and the charity). Altruistic motivation for deception reduced the intensity of moral conflict and the subsequent mental cost of resolving this conflict, reflected by a smaller N2–P3 effect in the purely altruistic condition. When making decisions about whether to lie, self-interest was a stronger motivator than others’ interests, and the participants tended to lie more for themselves than for others. When the lie could be mutually beneficial for both of the self and others, the participants tended to lie even when they knew that they could be easily caught, but they actually lied for their own self-interest rather than for altruistic reasons. These findings shed light on the neural basis of ‘good lies’ and decision-making in mutually beneficial situations.

Purpose: To investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal (HPA) axis hormones in acute stress reaction in rats with wound and combined local radiation injury. Methods: Sixty female Wistar rats (weighting 200 ± 20 g) were randomly divided into normal control group, wound group and combined wound-local radiation (CWR) group (25 Gy local radiation post wound), 20 rats in each group. Contents of IL-1β, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone (ACTH) and glucocorticoid (GC) in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation. Results: (1) The level of IFN-γ, one of the Th1 cell cytokines increased significantly at 14 d post CWR, which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1β and IL-6, one of the Th2 cell cytokines, did not show obvious change. (2) Ratio of Th1/Th2 (IFN-γ/IL-4) in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Th1/Th2 balance drifted to Th1 immune response. The ratio of Th1/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Th1/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. (3) Level of serous ACTH and GC in CWR group increased at 3 d post wound and radiation, and among them, level of GC showed statistically significant increase, which was much higher than that in control and wound groups. Conclusion: Level of serous neurohormone GC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes disturbance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR. Keywords: Radiation, Combined wound, Stress, Hypothalamo-pituitary-adrenal axis, Cytokines

Traumatic spinal cord injury (SCI) causes a cascade of degenerative events including cell death, axonal damage, and the upregulation of inhibitory molecules which prevent regeneration and limit recovery. Repulsive guidance molecule A (RGMa) is a potent neurite growth inhibitor in the central nervous system, exerting its repulsive activity by binding the Neogenin receptor. Here, we show for the first time that inhibitory RGMa is markedly upregulated in multiple cell types after clinically relevant impact-compression SCI in rats, and importantly, also in the injured human spinal cord. To neutralize inhibitory RGMa, clinically relevant human monoclonal antibodies were systemically administered after acute SCI, and were detected in serum, cerebrospinal fluid, and in the injured tissue. Rats treated with RGMa blocking antibodies showed significantly improved recovery of motor function and gait. Furthermore, RGMa blocking antibodies promoted neuronal survival, and enhanced the plasticity of descending serotonergic pathways and corticospinal tract axonal regeneration. RGMa antibody also attenuated neuropathic pain responses, which was associated with fewer activated microglia and reduced CGRP expression in the dorsal horn caudal to the lesion. These results show the therapeutic potential of the first human RGMa antibody for SCI and uncovers a new role for the RGMa/Neogenin pathway on neuropathic pain.

Background: In small fiber neuropathy (SFN), thinly myelinated Aδ and unmyelinated C fibers are primarily affected, resulting in sensory and/or autonomic symptoms. Various etiologies have been shown to be associated with SFN. This study was aimed to analyze a variety of features in peripheral neuropathy (PN) with small fiber involvement, and to compare disease severity among patients with idiopathic PN, PN associated with impaired glucose tolerance (IGT), and metabolic syndrome (MS) PN. Methods: Thirty-eight PN patients with small fiber involvement were enrolled from December 20, 2013 to May 31, 2016. Patients were divided into idiopathic PN, IGT-related PN, and MS-related PN groups. Detailed medical history and small fiber neuropathy were investigated, and symptom inventory questionnaire was conducted, as well as the visual analog scale. Nerve conduction studies and skin biopsies were also performed. The differences among the groups were analyzed using analysis of variance and Kruskal-Wallis test. Results: Eight patients were diagnosed with pure SFN. Intraepidermal nerve fiber density (IENFD) weakly correlated with motor conduction velocity (MCV) ( r = 0.372, P = 0.025), and proximal ( r = 0.383, P = 0.021) and distal ( r = 0.358, P = 0.032) compound muscle action potential (CMAP) of the tibial nerve. IENFD also weakly correlated with MCV of the peroneal nerve ( r = 0.399, P = 0.016). IENFD was shown to be significantly different among all groups ( χ 2 = 9.901, P = 0.007). IENFD was significantly decreased ( χ 2 = 23.000, P = 0.003) in the MS-related PN group compared to the idiopathic PN group. The MCV of the tibial nerve was significantly different among all groups ( χ 2 = 8.172, P F = 4.336, P = 0.021) and distal ( F = 3.262, P = 0.049) CMAP of the tibial nerve was also significantly different among all groups. Conclusions: IENFD of patients included in the present study weakly correlated with various electrophysiological parameters. Small and large fibers are more involved in patients with MS-related PN than in patients with idiopathic PN.

Two hypotheses have been proposed regarding the response that is triggered by observing others' pain: the "empathizing hypothesis" and the "threat value of pain hypothesis." The former suggests that observing others' pain triggers an empathic response. The latter suggests that it activates the threat-detection system. In the present study, participants were instructed to observe pictures that showed an anonymous hand or foot in a painful or non-painful situation in a threatening or friendly social context. Event-related potentials were recorded when the participants passively observed these pictures in different contexts. We observed an interaction between context and picture in the early automatic N1 component, in which the painful pictures elicited a larger amplitude than the non-painful pictures only in the threatening context and not in the friendly context. We also observed an interaction between context and picture in the late P3 component, in which the painful pictures elicited a larger amplitude than the non-painful pictures only in the friendly context and not in the threatening context. These results indicate that specific social contexts can modulate the neural responses to observing others' pain. The "empathic hypothesis" and "threat value of pain hypothesis" are not mutually exclusive and do not contradict each other but rather work in different temporal stages.

Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict the prognosis and treatment response. This study investigated whether circulating tumor cells (CTCs) detectable could reminder high risk of distant metastasis, provide prognostic information, and early indicate the response to the conventional therapy in patients with advanced NSCLC. In this single-center prospective study, blood samples for CTC analysis were obtained from 59 patients with previously untreated, stage III or IV NSCLC both before and after administration of two cycles of chemotherapy. CTCs took in peripheral blood were measured by Cell Search detect technique. Carcino-embryonic antigen and count of metastatic sites were positively related to CTC count analyzed by multiple linear regression (P

The present study investigated the time course of processing other's pain under different conditions of working memory (WM) load. Event-related potentials (ERPs) were recorded while the participants held two digits (low WM load) or six digits (high WM load) in WM and viewed pictures that showed others who were in painful or non-painful situations. Robust WM-load×Picture interactions were found for the N2 and LPP components. In the high WM-load condition, painful pictures elicited significantly larger amplitudes than non-painful pictures. In the low WM load condition, the difference between the painful and non-painful pictures was not significant. These ERP results indicate that WM load can influence both the early automatic N2 component and late cognitive LPP component. Compared with high WM load, low WM load reduced affective arousal and emotional sharing in response to other's pain and weakened the cognitive evaluation of task irrelevant stimuli. These findings are explained from the load theory perspective.

Cystic echinococcosis (CE) is a worldwide hazardous zoonotic parasitosis caused by Echinococcus granulosus. CE development involves complex immunological mechanisms, including participation of multiple immune cells and effector molecules. Myeloid-derived suppressor cells (MDSCs) are known to be involved in chronic and acute inflammatory conditions. In this study, we aimed to characterize the immune function of MDSCs in CE to improve the understanding, prevention and treatment of CE. Our results indicated that MDSCs overexpressing Ly6C and Ly6G inhibit the formation and activity of T helper 2 cells in a NO-dependent manner during E. granulosus infection.

Mind wandering has consistently been associated with impairments in cognition, emotion and daily performance. However, few experimental studies on mind wandering have been conducted in individuals with schizophrenia. The present study aimed to examine mind wandering in schizophrenia patients with a thought-sampling experiment embedded in a rapid go/no-go task and the relationship between the frequency of mind wandering and psychotic symptoms. Fifty-eight schizophrenia patients and 56 matched healthy controls were recruited and engaged in a task that assessed mind wandering. The results showed that schizophrenia patients (1.4%) reported less frequent mind wandering than healthy controls (5.8%). Moreover, there was no significant correlation between the frequency of mind wandering and psychotic symptoms in schizophrenia patients. Further studies in different stages of schizophrenia and in patients with more severe psychotic symptoms are needed to demonstrate a more comprehensive picture of mind wandering in schizophrenia.

Third-party punishment refers to the punishment imposed by a party whose benefit is not directly affected by any norm violations. The present study using a modified Dictator Game explored how social statuses of the involved parties modulate punishment decisions of a third-party. Systematic manipulation of the dictators’ and recipients’ status revealed that: higher recipient status correlated with more severe punishment, but no effect of the dictator’s. We further focused on the neural underlying of this effect using ERPs. An interaction of recipient's status × fairness was observed on MFN such that only for a high-status recipient, larger amplitude was triggered by unfair offers comparing to fair offers. On LPC, the largest amplitude was observed when the offer was fair and the recipient had medium-status. These findings suggested: participants consider unfair offers proposed to high-status recipients as more norm-violating and they may evaluate the offers from the perspective of the recipient.

Objective. To research the clinical characteristics and risk factors of lung cancer-associated acute ischemic stroke (LCA-AIS). Methods. Patients diagnosed with LCA-AIS, simple lung cancer, and simple AIS were enrolled. The primary information, laboratory results, tumor histopathology, neurological deficits, and survival time of the patients were collected and analyzed. Results. (1) In the LCA-AIS group, the pathology of 69.56% patients were adenocarcinoma, and the proportion of poorly differentiated patients was significantly more than that in moderately differentiated or highly differentiated. The number of stage IV lung cancer patients in the LCA-AIS group was significantly more common than in other stages. (2) 56.52% of patients with lung cancer were diagnosed before AIS, and the peak of AIS attack was 1–6 months after the diagnosis of lung cancer. (3) The independent risk factors of LCA-AIS were CYFRA-211 (OR 1.070; 95% confidence interval 1.005, 1.139; p=0.035), TT (OR 1.275; 95% confidence interval 1.089, 1.493; p=0.003), and Hct (OR 0.878; 95% confidence interval 0.779, 0.990; p=0.034), making ROC curve, suggesting the area under the curve is 0.871. (4) The neurological deficit of patients in the LCA-AIS group was similar to the simple AIS group and could not be identified by the severity of neurological deficits. (5) The median survival time of LCA-AIS group patients was five months (95% confidence interval 3.796, 6.204). There were statistical differences in survival time between LCA-AIS group and simple AIS group patients (p<0.001).Conclusions. The interaction between lung cancer and AIS may shorten patients’ life expectancy and worsen their quality of life.

This study explored specificity and visual perspective of mental time travel in schizophrenia. Fifteen patients with schizophrenia and 18 controls were recruited. Participants were asked to recall or imagine specific events according to cue words. Results showed that schizophrenia patients generated fewer specific events than controls, the recalled events were more specific than imagined events. Schizophrenia adopted less field perspective and more observer perspective than controls. These results suggested that patients with schizophrenia were impaired in mental time travel both in specificity and visual perspective. Further studies are needed to identify the underlying mechanisms.

The present study investigated how pain appraisals from other individuals modulated self-pain anticipation and perception. Appraisals of pain intensity from 10 other individuals were presented before the participants received identical electrical pain stimulation themselves. In reality, the presented other's pain appraisals, with either low or high in mean and variance, were generated by the experimenter, and were randomly paired with the subsequent electrical stimulation at either low or high intensity. Specifically, the mean and variance of others' pain appraisals were manipulated to induce participants' expectation and certainty to the upcoming pain. Subjective ratings of pain intensity and electroencephalographic (EEG) responses to the electrical stimulation, as well as anticipatory EEG activities measured prior to the onset of electrical stimulation, were compared. Results showed that the mean and variance of others' pain appraisal modulated the subjective pain ratings and the affective-motivational P2 responses elicited by the electrical stimulation, as well as anticipatory sensorimotor α-oscillation measured before the onset of pain stimulation. When the mean of others' pain appraisal was low, higher variance suppressed the sensorimotor α-oscillations and enhanced subsequent pain perception. In contrast, when the mean was high, the higher variance enhanced sensorimotor α-oscillations and suppressed subsequent pain perception. These results demonstrated that others' pain appraisals can modulate both of the anticipation and perception of first-hand pain. It also suggested that the top-down modulation of others' pain appraisals on pain perception could be partially driven by the different brain states during the anticipation stage, as captured by the prestimulus sensorimotor α-oscillations.

Hereditary spastic paraplegias are heterogeneous disorders with diversified clinical manifestations, and genetic testing is important for the diagnosis and typing of hereditary spastic paraplegias. Gene panel sequencing containing 55 hereditary spastic paraplegias-related genes was performed to screen the pathogenic genes for hereditary spastic paraplegias. Sanger sequencing was adopted to validate if the family member carried the same pathogenic gene as the proband. Fifteen out of 53 patients carried mutation(s) in the screened hereditary spastic paraplegias-related genes. Among the 23 identified mutations, only one mutation had been previously reported as a pathogenic mutation. In the pedigree of case 6, the proband, his mother and uncle all carried the same novel deletion mutation (c.1459delA) at SPAST gene. Based on the pedigree, the disease was inherited in an AD pattern. In the pedigree of case 53, the family disease may be in an X-linked recessive inheritance pattern. The proband (case 53) carried two novel mutations in ALT1 gene and L1CAM gene (c.2511C>A), respectively. The L1CAM gene is the causative gene for the SPG1 X-linked recessive—hereditary spastic paraplegias. Our data confirm the genetic heterogeneity of hereditary spastic paraplegias, and SPG4/SPAST were the most frequent forms. The pathogenicity of the novel mutations is worth to be further investigated.

Background S100A9 protein, which is recently classified as a novel damage associated molecular pattern, is released from stressed cells undergoing necrosis or secreted by living cells undergoing a stress that act as endogenous danger signal associated with infection, tissue damage and cancer. Here, we evaluated the relationship of serum S100A9 with viral replication and liver necroinflammation in patients with chronic hepatitis B (CHB) infection. Methods A total of one hundred and eighty-three recruited patients with CHB infection underwent liver biopsy for grading of necroinflammation (G) and staging of fibrosis (S). Forty-nine healthy individuals were included as healthy controls (HCs). Serum S100A9 levels were determined by enzyme-linked immunosorbent assay. Correlations of serum S100A9 with viral replication and liver necroinflammation were analyzed. The receiver operating characteristic curve was used to assess the discriminating power of serum S100A9 to grade liver necroinflammation (G). Liver normal L02 cells were transfected with a HBV plasmid, and S100A9 levels were determined. Results Serum S100A9 levels were increased in CHB patients compared to HCs. Intrahepatic immunoreactivity for S100A9 was enhanced in liver sample from CHB patients. Infection of HBV also resulted in an elevated S100A9 expression in L02 cells. Serum S100A9 was correlated with the serum HBV DNA levels. CHB patients with moderate-to-severe liver necroinflammation (G ≥ 2) showed significantly higher serum S100A9 levels than those without or with mild necroinflammation (G

Tamoxifen, a selective estrogen receptor (ER) modulator, is the most widely used endocrine therapy for patients with ER‑positive breast cancer. However, ~30% of tamoxifen‑treated breast cancers do not initially respond to tamoxifen, and neither do they eventually develop tamoxifen resistance. Bcl‑2‑associated athanogene 1 (BAG‑1) is a multifunctional protein that interacts with a wide range of molecules to protect cells from apoptosis otherwise induced by cytotoxic drugs, growth factor withdrawal, radiation and stress. The aim of the present study was to investigate the function of BAG‑1 in tamoxifen resistance. Immunohistochemistry techniques were used to determine BAG‑1 expression in 119 stage I‑III primary breast cancer tissues and it was identified that BAG‑1 was significantly overexpressed in ER‑positive breast cancer (P=0.001). Knockdown of BAG‑1 by short interfering RNA was revealed to downregulate ER, and upregulate phospho (p)‑protein kinase B (Akt) and p‑mammalian target of rapamycin (mTOR) levels. Furthermore, significantly decreased tamoxifen‑induced apoptosis (41.70±1.93 vs. 55.03±2.39%; P=0.012) was observed in T47D cells following the silencing of BAG‑1. In contrast, overexpression of BAG‑1 long enhanced apoptosis (65.10±2.35 vs. 55.03±2.39%; P=0.039) in T47D cells treated with tamoxifen. Combination treatment of tamoxifen and an mTOR inhibitor restored the inhibitory effects of tamoxifen in T47D cells exhibiting low BAG‑1 expression levels (66.87±2.27 vs. 57.07±2.46%; P=0.037). In conclusion, there results of the present study indicated that suppression of BAG‑1 expression may activate the phosphoinositide 3‑kinase/Akt/mTOR pathway and protect ER‑positive breast cancer cells from tamoxifen‑induced inhibition of proliferation. ER‑positive breast cancer cells exhibiting low BAG‑1 expression appeared to be more sensitive to treatment with the mTOR inhibitor rapamycin. Furthermore, the results indicated that combination treatment targeting ER with tamoxifen and targeting mTOR with rapamycin may significantly potentiate the inhibitory effect in BAG‑1‑silenced cells.

To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS. Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner’s corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition. Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P

Introduction: Prospective memory (PM) refers to remembering to execute a planned intention in the future. It can be divided into event- and time-based, according to the nature of the PM cue. Event-based PM cues can be classified as focal or non-focal. Patients with schizophrenia (SCZ) have been found to be impaired in both event- and time-based PM. PM has been found to be improved by implementation intentions, which is an encoding strategy in the format of “if X then Y”. This study examined the effect of implementation intentions on a non-focal event-based and a time-based PM task in patients with SCZ.Methods: Forty-two patients with SCZ and 42 healthy controls were allocated to either an implementation intention or a control PM instruction condition and were asked to complete two PM tasks. Results: Implementation intentions was found to improve performance in both the non-focal event-based and time-based PM tasks in patients with SCZ and healthy controls, with no costs to the ongoing task. The improvement in time-based PM performance in the implementation intentions condition was partially mediated by the frequency of clock checking behaviour. Conclusions: Implementation intentions can facilitate PM performance in patients with SCZ and has the potential to be used as a clinical intervention tool.

The aim of this study is to investigate the neural mechanism of country-of-origin image (COI) stereotype in product evaluation. A watch purchasing experiment was conducted and electroencephalogram (EEG) was recorded while participants making purchasing decisions. Switzerland was chosen as COI stereotype-congruent country; Belgium, France and Denmark were chosen as COI stereotype-incongruent countries of watches. Event-related potential (ERP) data showed remarkable augmented P200 amplitudes and attenuated N270 in stereotype-congruent group than that in stereotype-incongruent group. P200 is associated with unconscious implicit emotional priming of stereotype. N270 not only reflects cognitive monitoring but also connects with behavioral control in stereotype-based decision making. In contrast to previous neuropsychological findings on racial stereotype and gender stereotype, our data suggest stereotype in product judgement may share the same automatic stereotype activation process on P200 with person judgement. But the cognitive monitoring mechanism of stereotype may be more sensitive in product evaluation (reflecting on N270) than in person evaluation (reflecting on N400 in previous research).

Here we examine whether brain responses to dynamic facial expressions of pain are influenced by our responsibility for the observed pain. Participants played a flanker task with a confederate. Whenever either erred, the confederate was seen to receive a noxious shock. Using functional magnetic resonance imaging, we found that regions of the functionally localized pain-matrix of the participants (the anterior insula in particular) were activated most strongly when seeing the confederate receive a noxious shock when only the participant had erred (and hence had full responsibility). When both or only the confederate had erred (i.e. participant's shared or no responsibility), significantly weaker vicarious pain-matrix activations were measured., Graphical abstract Summary figure: (A) Participants believed to perform a flanker task in the scanner, while FC, supposedly another participant, was doing the same task, at the same time, in another room. For each trial, the performances of FC and participant were shown to both. Whenever either or both erred, FC received a noxious shock, and the participant saw her reaction through a CCTV feed (B top). If both performed correctly, an innoxious shock was delivered (B bottom). Brain activation measured in the participant while watching the painful CCTV feed was stronger when only the participant had erred, and therefore had full responsibility for the shock compared to conditions in which both had erred, and responsibility was shared (C). A pain localizer in which the participant received electroshocks and evaluated how unpleasant they were revealed regions involved in experiencing the unpleasantness of pain (D). Importantly, some of the regions in which responsibility influenced brain activity to the video overlapped with the pain localizer (yellow in E, including ACC and Insula), supporting that affective other-pain processing is reduced if responsibility for that pain is shared., Highlights • Responsibility modulates empathy related brain responses. • Being fully responsible for another's pain increases activity in the witness' pain-matrix. • Sharing responsibility or not being responsible reduces pain-matrix activity.

S100A9 belongs to the S100 family of calcium-binding proteins and is over-expressed in many human tumors including hepatocellular carcinoma (HCC). Recent study demonstrated that S100A9 is significantly elevated and is associated with tumor differentiation and vascular invasion in HCC. The functional role of S100A9 is, however, poorly understood. Here, we demonstrated that S100A9 treatment increased viability, invasiveness and clone formation in three HCC cell lines (HepG2, SMMC-7721 and Huh7). S100A9 also promoted tumor growth in vivo by a xenograft mouse model. In addition, we observed a co-localization of S100A9 with receptor for advanced glycation end products (RAGE) in human HCC intratumoral tissues and an interaction of S100A9 with RAGE in vitro. Treatment with RAGE blocking antibody blocked the enhanced viability, invasion, clone formation and tumor growth in vivo resulted by S100A9, suggesting that these effects were mediated via RAGE ligation. In order to investigate the signaling pathways, mitogen-activated protein kinase (MAPK) phosphorylation was characterized. S100A9 caused a significant increase in p-p38 and p-ERK1/2 levels, and inhibition of which blocked enhanced invasion and viability resulted by S100A9, respectively. Furthermore, treatment with RAGE blocking antibodies also abrogated the S100A9-induced p38 and ERK1/2 activation, suggesting that S100A9-induced MAPK activation is mediated via RAGE ligation. Our data demonstrate that S100A9 binds to RAGE and stimulates RAGE-dependent MAPK signaling cascades, promoting cell growth and invasion in HCC.

Summary Repulsive guidance molecule A (RGMa) is a potent inhibitor of neuronal regeneration and a regulator of cell death, and it plays a role in multiple sclerosis (MS). In autopsy material from progressive MS patients, RGMa was found in active and chronic lesions, as well as in normal-appearing gray and white matter, and was expressed by cellular meningeal infiltrates. Levels of soluble RGMa in the cerebrospinal fluid were decreased in progressive MS patients successfully treated with intrathecal corticosteroid triamcinolone acetonide (TCA), showing functional improvements. In vitro, RGMa monoclonal antibodies (mAbs) reversed RGMa-mediated neurite outgrowth inhibition and chemorepulsion. In animal models of CNS damage and MS, RGMa antibody stimulated regeneration and remyelination of damaged nerve fibers, accelerated functional recovery, and protected the retinal nerve fiber layer as measured by clinically relevant optic coherence tomography. These data suggest that targeting RGMa is a promising strategy to improve functional recovery in MS patients.

Myasthenia gravis (MG) is an autoimmune disease commonly treated with immunosuppressants. We evaluated the novel immunosuppressant, rapamycin (RAPA), in a rat model of experimental autoimmune MG (EAMG). Mortality rates in the RAPA (12%) were significantly down compared with the EAMG (88%) or cyclophosphamide (CTX) (68%) intervention groups. Muscular weakness decreased after both RAPA and CTX treatment. However, Lennon scores were lower (1.74 ± 0.49, 3.39 ± 0.21, and 3.81 ± 0.22 in RAPA, CTX, and EAMG groups, respectively), and body weights (203.12 ± 4.13 g, 179.23 ± 2.13 g, and 180.13 ± 5.13 g in RAPA, CTX, and EAMG groups, respectively) were significantly higher, only in the RAPA group. The proportion of regulatory T cells (Treg) significantly increased, while that of Th17 cells significantly decreased in the RAPA group compared with the EAMG group. In comparison, CTX intervention resulted in increased Th17 but significantly decreased Tregs. Hence, RAPA can be more effectively used in comparison with CTX to treat MG, with an efficacy higher than that of CTX. In addition, our results suggest RAPA’s efficacy in alleviating symptoms of MG stems from its ability to correct the Treg/Th17 imbalance observed in MG.

Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery, which leads to severe disabilities in motor functions or pain. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration. In the present study, we describe the cloning, functional expression in Escherichia coli cells and purification of a recombinant αL1 Fab fragment that binds to L1 with comparable activity as the function-triggering monoclonal antibody 557.B6 and induces neurite outgrowth and neuronal survival in cultured neurons, despite its monovalent function. Infusion of αL1 Fab into the lesioned spinal cord of mice enhanced functional recovery after thoracic spinal cord compression injury. αL1 Fab treatment resulted in reduced scar volume, enhanced number of tyrosine hydroxylase-positive axons and increased linear density of VGLUT1 (vesicular glutamate transporter 1) on motoneurons. Furthermore, the number and soma size of ChAT (choline acetyltransferase)-positive motoneurons and the linear density of ChAT-positive boutons on motoneurons as well as parvalbumin-positive interneurons in the lumbar spinal cord were elevated. Stimulation of endogenous L1 by application of the αL1 Fab opens new avenues for recombinant antibody technology, offering prospects for therapeutic applications after traumatic nervous system lesions. Abbreviations: BBB, Basso, Beattie, Bresnahan; ChAT, choline acetyltransferase; CNS, central nervous system; FNIII, fibronectin-type III; GABA, γ-aminobutyric acid; GFAP, glial fibrillary acidic protein; HRP, horseradish peroxidase; IMAC, immobilized metal-ion-affinity chromatography; mAb, monoclonal antibody; MBP, myelin basic protein; NCAM, neural cell adhesion molecule; Nogo, neurite outgrowth inhibitor; PLL, poly-L-lysine; PV, parvalbumin; SEC, size-exclusion chromatography; TEV, tobacco etch virus; TH, tyrosine hydroxylase; VGAT, vesicular GABA; VGLUT1, vesicular glutamate transporter 1