AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

Objective : To investigate the expression and biological function of circular RNA(circRNA) hsa＿circ＿0002938 in gastric cancer. Methods : 45 pairs of tumor tissues and para-cancerous tissues from gastric cancer patients who underwent tumor reduction surgery at the hospital were collected. Human gastric cancer cells SGC-7901, BGC-823, HGC-27, MGC-803 and immortalized gastric mucosal epithelial cells GES-1 were routinely cultured. RT-qPCR was utilized to detect the expression of hsa＿circ＿0002938 in gastric cancer tissues and cells. Chi-square test was used to analyze its association with the clinicopathological characteristics of patients, and the Kaplan-Meier method was employed to assess the relationship between hsa＿circ＿0002938 expression levels and patient prognosis. The effects of hsa＿circ＿0002938 on the proliferation, migration and invasion abilities of gastric cancer cells were detected by CCK-8, scratch wound healing and Transwell assays. Bioinformatics was used to predict the miRNA and its downstream target genes that hsa＿circ＿0002938 might bind to. The competitive endogenous RNA regulatory network was constructed and the functions of the target genes were enriched. Results : The expression of hsa＿circ＿0002938 in gastric cancer tissues and cells was much higher than that in para-cancerous tissues and GES-1 cells(P<0.05). By contrast, patients in the high hsa＿circ＿0002938 expression group had significantly shorter 2-year progression-free survival than that in the low expression group after surgery(P<0.01). Moreover, knocking down the expression of hsa＿circ＿0002938 reduced the proliferative, migratory, and invasive abilities of gastric cancer cells(P<0.05). Bioinformatics predictive analysis showed that hsa＿circ＿0002938 could bind to hsa-miR-342-3p and hsa-miR-503-5p. The downstream target genes of miRNA were involved in several cancer-related pathways, like mitogen-activated protein kinase(MAPK), hippo and Wnt signaling pathway. Conclusion Hsa＿circ＿0002938, which is highly expressed in gastric cancer tissues and cells, is closely associated with poor patient prognosis. Knockdown of hsa＿circ＿0002938 inhibits the proliferation, migration, and invasion abilities of gastric cancer cells. The study reveals the potential role of hsa＿circ＿0002938 in the progression of gastric cancer, offering new insights into its prevention and treatment.

Objective To explore the effect of repetitive transcranial magnetic stimulation(rTMS)on the sleep disorder and examination results of recruits.Methods At a training base,the Pittsburgh Sleep Quality Index(PSQI)was used to screen the recruits with sleep disorders(total score of PSQI>7).The recruits were randomly assigned to rTMS group or sham rTMS group.Both groups received cognitive and behavioral intervention therapy,including sleep health education and relaxation training.Moreover,the rTMS group was treated with rTMS at the right posterior parietal lobe by continuous theta burst stimulation(cTBS)twice a day at an interval of at least 50 min for 5 consecutive days as a course of treatment with an interval of 2 days for a total of 2 courses of treatment.The coil position and stimulus intensity of sham rTMS group were consistent with the rTMS group,but the head of subjects was perpendicular to the coil plane and there was no effective stimulation.Before and after treatment,PSQI,self-rating depression scale,generalized anxiety disorder-7 and health questionnaire-15 were used to evaluate the sleep,mood and physical state of the recruits.The training result was assessed one month after treatment.The total effective rate of PSQI improvement and examination results were compared between the two groups.The independent influencing factors of excellent examination result were analyzed.Results Among 351 recruits,83 with sleep disorders completed treatment and follow-up.There were 40 patients in the rTMS group and 43 patients in the sham rTMS group.There was no significant difference between the two groups at baseline.After treatment,the total effective rate of PSQI improvement in the rTMS group was higher than that in the sham rTMS group(77.50%vs 53.49%,P=0.022).The average examination score and excellent rate of the rTMS group were higher than those of the sham rTMS group(91.58±3.19 vs 89.47±4.67,P=0.020;85%vs 65.12%,P=0.037).Logistic regression analysis showed that the treatment mode(rTMS group)was the independent influencing factor of excellent examination results(P=0.032).Conclusion rTMS can effectively and safely improve the sleep disorders and examination results of recruits.rTMS may play a positive role in improving the learning and training effect of recruits,which needs to be further proved.

Objective To explore the effects of sigma-1 receptor(Sig-1R)on brain function in rats after cardiopulmo-nary resuscitation and its protective role in brain injury.Methods Rats were randomly assigned to four groups with 20 in each:sham-operated control(sham group),6-hour post-resuscitation(PR 6 h group),12-hour post-resuscitation(PR 12 h group)and 24-hour post-resuscitation(PR 24 h group).In the latter three groups,cardiac arrest was induced by as-phyxiation,and cardiopulmonary resuscitation was performed 6 minutes after cardiac arrest.The rats were scored for neu-rological deficits at 6,12 and 24 hrs after resuscitation,respectively;after that,the rats were executed,and the expres-sion of Sig-1R protein,mitochondrial function index,and endoplasmic reticulum stress index apoptosis index were detec-ted by Western blot and immunohistochemistry.The correlation between Sig-1R and mitochondrial,endoplasmic reticulum stress and apoptosis indexes was evaluated.Results Compared with the sham-operated group,the rats in test group showed a gradual decrease in neurological deficit scores,Sig-1R protein expression,brain tissue adenosine triphos-phate(ATP)concentration and mitochondrial membrane potential(MMP)levels at 6,12,and 24 hrs of PR(P＜0.05);CHOP protein,activated cleaved caspase-12 and cleaved caspase-3 protein expression were consistently elevated(P＜0.05).In addition,Sig-1R was negatively correlated with brain tissue endoplasmic reticulum stress and apoptosis(P＜0.05)but positively correlated with mitochondrial membrane potential level(P＜0.05).Conclusions Sig-1R ex-pression in rat brain tissue correlates with brain injury after cardiopulmonary resuscitation and potential mechanism seems to be neuronal protection through modulating mitochondrial function and endoplasmic reticulum stress.

Mental disorders pose a significant challenge to global public health,profoundly affecting the quality of life of a vast number of individuals and imposing a heavy health burden on society.Nonetheless,there remains a substantial gap between the current societal capacity to provide prevention,diagnosis,and treatment for mental disorders and the existing demand for such services.In recent years,the development and application of artificial intelligence(AI)technologies have provided unprecedented opportunities to enhance mental healthcare services.As one of the fastest-growing fields of AI,generative AI has played a pivotal role in analyzing diverse forms of data,including medical image processing,protein structure prediction,clinical document generation,auxiliary diagnostic discrimination,and clinical decision support.These advancements have significantly strengthened capabilities in clinical diagnosis,data reconstruction,and adjunctive therapeutic interventions.This review highlights the potential applications of generative AI in advancing fundamental psychiatric research,identifying early risk factors for mental disorders,and assisting clinicians in diagnosis and treatment.Additionally,it addresses the challenges and limitations currently facing the application of generative AI to mental healthcare,including biases,privacy breaches,and insufficient interpretability.Finally,the review summarizes strategies to enhance AI's capacity to deliver mental health services,aiming to leverage new technologies to reduce the global burden of mental disorders and improve the quality of life of affected individuals.

Mental disorders pose a significant challenge to global public health,profoundly affecting the quality of life of a vast number of individuals and imposing a heavy health burden on society.Nonetheless,there remains a substantial gap between the current societal capacity to provide prevention,diagnosis,and treatment for mental disorders and the existing demand for such services.In recent years,the development and application of artificial intelligence(AI)technologies have provided unprecedented opportunities to enhance mental healthcare services.As one of the fastest-growing fields of AI,generative AI has played a pivotal role in analyzing diverse forms of data,including medical image processing,protein structure prediction,clinical document generation,auxiliary diagnostic discrimination,and clinical decision support.These advancements have significantly strengthened capabilities in clinical diagnosis,data reconstruction,and adjunctive therapeutic interventions.This review highlights the potential applications of generative AI in advancing fundamental psychiatric research,identifying early risk factors for mental disorders,and assisting clinicians in diagnosis and treatment.Additionally,it addresses the challenges and limitations currently facing the application of generative AI to mental healthcare,including biases,privacy breaches,and insufficient interpretability.Finally,the review summarizes strategies to enhance AI's capacity to deliver mental health services,aiming to leverage new technologies to reduce the global burden of mental disorders and improve the quality of life of affected individuals.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

Since the proposal of the concept of the gut-liver axis,a large number of studies have focused on exploring the connection between gut microbiota and liver disease;however,the idea of using pyroptosis as a hub to explore the intrinsic mechanism of gut-liver crosstalk is still in its infancy.This article mainly describes the process by which gut microbiota dysbiosis affects the integrity of mucosal barrier and bile acid metabolism,induces pyroptosis,and thereby affects the development and progression of liver diseases,and it also concludes that gut microbiota dysbiosis affects liver diseases by inducing NLRP3/AIM2/Caspase-1-dependent,Caspase-4/11/GSDMD-dependent,and Caspase-3/GSDME-dependent pyroptosis.In summary,this study aims to provide new ideas and targets for the future diagnosis and treatment of liver diseases by establishing the connection between pyroptosis and intestinal-liver immune crosstalk.

Background The staff in centers for disease control and prevention (CDC) were at a great risk for psychological distress when they were faced with outbreak-related prevention and control work and routine tasks during the COVID-19 period. Psychological resilience and burnout are two key influencing factors on psychological distress. Objective To explore the status and mechanisms of psychological resilience, burnout, and psychological distress among CDC staff. Methods From September to October 2022, a cross-sectional survey was conducted in all CDC staff in Beijing, and 2228 CDC staff from 17 units (including 1 municipality-level CDC and 16 district-level CDCs) participated the questionnaire survey. The basic information questionnaire, Connor-Davidson Resilience Scale (CD-RISC-10) Chinese version, Maslach Burnout Inventory-General Survey (MBI-GS) Chinese version, and the 10-item Kessler Psychological Distress Scale (Kessler10) Chinese version were selected in our study. Mann-Whitney U test or Kruskal-Wallis H test was used to analyze the differences in the scores of psychological resilience, burnout, and psychological distress by demographic and sociological characteristics. The correlations among the three elements were analyzed by Spearman correlation analysis. Potential influencing factors of psychological distress of the CDC staff were evaluated by multiple linear regression. A potential mediating effect of psychological resilience-burnout-psychological distress was analyzed by the mediation package of R 4.2.0, and validated by Bootstrap method. Results Of 2228 questionnaires distributed, 2022 valid questionnaires were collected, and the recovery rate was 90.75%. The median (P₂₅, P₇₅) psychological distress score of CDC staff was 13.00 (8.00, 24.00), and the number of participants with psychological distress levels of 1, 2, 3, and 4 was 358 (17.71%), 546 (27.00%), 362 (17.90%), and 756 (37.39%), respectively. The median (P₂₅, P₇₅) psychological resilience score was 24.00 (20.00, 30.00) and the median (P₂₅, P₇₅) burnout score was 38.00 (25.00, 50.00). The results of the multiple linear regression showed that psychological resilience, burnout, caring for the elderly, having a chronic disease, and monthly income had independent influences on psychological distress (P<0.05), and emotional exhaustion, cynicism, and reduced personal accomplishment (reversed) in the case of burnout had a great effect on psychological distress (P<0.05). After controlling general demographic characteristic variables, total burnout score exerted a partial mediation effect on the relationship between psychological resilience and psychological distress, with a mediation effect value of −0.439 (95%CI: −0.483, −0.397), and a total mediation effect contribution rate of 60.89%. The two dimensions of burnout (emotional exhaustion and cynicism) played a partial mediating role between psychological resilience and psychological distress, with mediating effect contribution rates of 42.44% and 41.41%, respectively. Conclusion Psychological distress among CDC staff in Beijing was prominent during COVID-19. Psychological resilience can act directly on psychological distress or indirectly on psychological distress through burnout. Both emotional exhaustion and cynicism dimensions of burnout have a partial mediating role between psychological resilience and psychological distress. Increasing psychological resilience and decreasing burnout may reduce the occurrence of psychological distress.

Objective To investigate the effects of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα protein in peripheral blood CD4+Th1 cells of healthy control subjects(HC)and patients with allergic rhi-nitis(AR),and on the expressions of IL-18,IL-18BPa and IL-18Rα mRNA in the peripheral blood CD4+T cells.Methods Blood samples were collected from patients with rhinitis for negative skin prick test(AR-),rhinitis for positive skin prick test(AR+)and HC.Flow cytometry was used to evaluate the effects of allergens on the expres-sions of IL-18,IL-18BPa and IL-18Rα protein in CD4+Th1 cells.The expressions of IL-18,IL-18BPa and IL-18Rα mRNA in CD4+T cells were determined by qPCR.Results Compared with HC,increased IL-18 while de-creased IL-18BPa expressions in Th1 cells of AR-and AR+patients were observed,increased IL-18Rα expression in Th1 cells of AR+patients was also found.Additionally,allergens induced elevated expression of IL-18Rα pro-tein in Th1 cells of HC,and induced elevated mRNA expressions of IL-18,IL-18BPa and IL-18Rα in isolated blood CD4+T cells of AR+patients and HC.Conclusion Allergens may be involved in the pathogenesis of AR by inducing the expressions of IL-18 and IL-18Rα in blood CD4+Th1 cells.