BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However， the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder， and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently， 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory （BDI） and Beck Anxiety Inventory （BAI） were used for assessment， and decision-making behavior was evaluated using Probabilistic Reversal Learning （PRL） task. Indicators assessed included the number of trials to criterion， perseverative errors， win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group （t=3.684， P<0.01）. There were no statistically significant differences between two groups in trials to criterion， perseverative errors and win-stay rate （t=0.329， 0.132， 0.609， P>0.05）. In depression group， BDI and BAI scores were positively correlated with the win-stay rate（r=0.450， 0.398， P<0.01）. ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore， the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. ［Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University （number， 2019LZXNYDJ39］

Background Metacognition,the capacity to monitor and control one's cognitive processes,has been identified as a crucial component of effective decision-making and behavioral adaptation.Previous research has revealed cognitive deficits in patients with major depressive disorder(MDD),while findings about metacognitive capacities in patients with MDD have been inconsistent across studies,and the exact relationship between metacognitive capacities and clinical symptoms in MDD patients remains uncertain.Objective To examine the metacognitive capacities of adolescent hospitalized patients with MDD and to explore its relationship with depressive and anxiety symptoms,thus providing an unprecedented insight into the prevention of MDD.Methods A coherent 56 adolescent hospitalized patients with MDD in the Psychiatry Department at the Affiliated Hospital of Southwest Medical University from March 2022 to June 2023 and met the diagnostic criteria for depression as defined by the Diagnostic and Statistical Manual of Mental Disorders,fourth edition(DSM-IV)were enrolled as MDD group.At the same time,62 healthy individuals matched with the age and sex of the MDD group residing in Luzhou were concurrently selected as control group.The metacognitive ability of the two groups was evaluated by perceptual decision-making task and confidence rating task,and the indicators included confidence deviation,reaction time of confidence evaluation and metacognitive efficiency.Additionally,the severity of depressive and anxiety symptoms was measured with Beck Depression Inventory(BDI)and Beck Anxiety Inventory(BAI).Pearson correlation analysis was utilized to examine the relationship between metacognitive capacities and clinical symptoms.Results MDD group scored higher on BDI and BAI when compared with control group(t=-13.722,-9.674,P<0.01).In terms of decision-making performance,no statistically significant difference was noted in accuracy and response time between two groups(t=-0.655,0.975,P>0.05).In terms of metacognitive performance,MDD group reported a reduction in overall confidence,confidence in correct decisions,confidence in incorrect decisions and metacognitive efficiency compared with control group(t=3.044,2.769,2.836,3.667,P<0.01).MDD group demonstrated significantly longer confidence evaluation response time than that of control group(t=-2.561,P<0.05).Correlation analysis revealed that among the MDD patients,overall confidence,confidence in correct decisions and confidence in incorrect decisions were negatively correlated with BDI score(r=-0.310,-0.307,-0.298,P<0.05),and the overall confidence and confidence in correct decisions were negatively correlated with BAI score(r=-0.284,-0.280,P<0.05),while no statistical significance existed in the correlation between confidence in incorrect decisions and BAI score(r=-0.229,P>0.05).Furthermore,metacognitive efficiency in MDD patients exhibited negative correlation with both BDI and BAI scores(r=-0.269,-0.290,P<0.05).Conclusion Hospitalized adolescent patients with MDD have impaired metacognition,and metacognitive capacity is found to be associated with severity of depressive and anxiety symptoms.

Objective:To investigate the correlations of myasthenia gravis (MG) susceptibility with STAT3 (rs744166 and rs1053005) and STAT4 (rs7574865) gene polymorphisms. Methods:A total of 149 MG patients admitted to Department of Neurology, Second Affiliated Hospital of Harbin Medical University from September 2019 to June 2022 were selected as MG group, and 148 subjects accepted physical examination in our hospital at the same period were selected as control group. Peripheral venous blood of all subjects was collected. Improved multiplex ligation detection reaction (imLDR) assay was used to detect the STAT3 (rs744166 and rs1053005) and STAT4 (rs7574865) gene polymorphisms. Differences in polymorphisms of various gene loci were compared between the MG group and control group, among subjects with different gender or age, between MG patients with and without thymoma, between AChR-Ab positive and AChR-Ab negative MG patients, and between patients with eye muscle MG and systemic MG. Results:(1) Compared with the control group, the MG group had significantly increased GT and TT genotype and T allele frequencies (37.2% vs. 57.0%; 10.1% vs. 11.4%; 28.7% vs. 39.9%), and decreased GG genotype and G allele frequencies (52.7% vs. 31.5%; 71.3% vs. 60.1%) at rs7574865 locus in STAT4 gene ( P<0.05). (2) Compared with male subjects in the control group, the male patients in MG group had significantly increased GT and TT genotype and T allele frequencies, and decreased GG genotype and G allele frequencies at rs7574865 locus in STAT4 gene ( P<0.05); compared with female subjects in the control group, the female patients in MG group had significantly increased GT and TT genotype frequencies and decreased GG genotype frequency at rs7574865 locus in STAT4 gene ( P<0.05). Compared with subjects≤50 years old in the control group, patients≤50 years old in the MG group had significantly increased GT and TT genotype and T allele frequencies, and decreased GG genotype and G allele frequencies at rs7574865 locus in STAT4 gene ( P<0.05); compared with subjects>50 years old in the control group, patients>50 years old in the MG group had significantly increased GT genotype frequency and decreased GG and TT genotype frequencies at rs7574865 locus in STAT4 gene ( P<0.05). (3) No significant differences in genotype and allele frequencies were noted between MG patients with and without thymoma, between AChR-Ab positive and AChR-Ab negative MG patients, or between patients with eye muscle MG and systemic MG ( P>0.05). Conclusion:MG susceptibility is associated with rs7574865 polymorphism of STAT4 gene; the male subjects or subjects≤50 years old with GT/TT genotype or T allele are susceptible to MG.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective To predict the intervention targets of empagliflozin(EMPA),a specific inhibitor of sodium-glucose cotransporter 2(SGLT2),in gastric adenocarcinoma through comprehensive network pharmacology,and to validate the effects and the molecular mechanisms of EMPA through cellular and molecular biology experiments.Methods Bioinformatics analysis of gastric adenocarcinoma was conducted to assess the correlation between gastric adenocarcinoma prognosis and SGLT2 expression.Network pharmacology was utilized to identify shared targets of EMPA and gastric adenocarcinoma.AGS cells,a human gastric adenocarcinoma cells line,were incubated with EMPA at different concentrations for 24 h and,then,cell proliferation was assessed using the CCK8 assay.After AGS cells were incubated with EMPA at the doses of 0,3,and 6 mmol/L,real-time cell analysis(RTCA)and 5-ethynyl-2-deoxyuridine(EdU)incorporation were used to evaluate EMPA's inhibitory effects on the proliferation of the AGS cells.In addition,wound healing and Transwell assays were performed to assess the inhibitory effect of EMPA on the migration and invasion of the APC cells and Western blot analysis was conducted to examine the expression of mammalian target of rapamycin(mTOR)and phosphorylated mTOR(p-mTOR).BALB/c(nu/nu)nude mice were implanted with 5x106 AGS cells in the axilla.The mice were divided into three groups,a control group,a low-dose group,and a high-dose group,each consisting of 7 mice.After one week,the control group received daily intraperitoneal injections of normal saline,while the low-dose group and high-dose group received daily intraperitoneal injections of EMPA at the doses of 3 mg/kg and 5 mg/kg,respectively.The tumor volume was measured one week after the drug intervention started.Results Gastric adenocarcinoma patients with low expression of SGLT2 exhibited longer survival time and higher survival rate than those with high expression of SGLT2 did.A total of 104 EMPA-related potential targets and 2028 targets associated with gastric adenocarcinoma were identified.Among these,45 targets associated with gastric adenocarcinoma overlapped with potential targets of EMPA.Further analysis revealed 10 relevant pathways and 4 core genes.The core genes were cyclin-dependent kinase 4(CDK4),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),mTOR,and cyclin El(CCNE1).CCK-8 assay revealed that EMPA at concentrations ranging from 0.39 to 50 mmol/L effectively inhibited the proliferation of AGS cells.RTCA results indicated a downward shift in the cell growth curve.In comparison to the findings for the control group,EdU assay demonstrated that EMPA at the concentrations of 3 mmol/L and 6 mmol/L significantly inhibited AGS cell proliferation(P＜0.05).Results from wound healing and Transwell assays indicated a decrease in the levels of cell migration and invasion(P＜0.05)and,notably,there was a significant difference between the high and low-dose EMPA groups(P＜0.05).Western blot showed no statistically significant difference in the expression of total mTOR protein between the groups.However,the expression of p-mTOR in the 3 mmol/L and 6 mmol/L EMPA groups decreased compared to that of the control group(P＜0.05),with the 6 mmol/L EMPA group exhibiting a more pronounced reduction(P＜0.05).Nude mice xenograft tumor experiment demonstrated that,compared to that of the control group,the tumor volumes in the EMPA-treatment groups were significantly reduced(P＜0.05),with the high-dose group showing a more pronounced reduction(P＜0.05).Conclusion EMPA inhibits the abnormal proliferation and migration of gastric adenocarcinoma cells,potentially through the modulation of mTOR protein activation.This study provides new potential medication and intervention targets for gastric adenocarcinoma treatment.