Objective To investigate the synergistic therapy effects of B and T lymphocyte attenuator(BTLA) extracellular domain in combination with heat shock protein 70 (HSP70)-TC-1 antigen peptide complex on the mouse model of cervical cancer and the related immunological mechanisms. Methods(1)Detecting the BTLA and herpesvirus entry mediator (HVEM) gene expression in the tumor microenvironment after C57BL/6 mice were inoculated with TC-1 tumor cells by realtime PCR; BTLA,HVEM expression on tumor infiltrating lymphocytes cell surface were detected by flow cytometry (fluorescence intensity). (2) According to different treatments, tumor-bearing mice were divided into 5 groups, which was injected with pcDNA3. 1 (empty vector plasmid as control), psBTLA (vector plasmid which expresses BTLA extracellular domain), HSP70 (HSP70-TC-1 cell peptide complex), HSP70 +pcDNA3.1 or HSP70 + psBTLA, respectively. The weight of tumor was recorded. The expression of immunoregulatory genes in tumor microenvironment were detected. The change of lymphocyte amount and cytotoxicity were detected too; lymphocyte proliferation activity was measured by tritium thymidine incorporation assay; the concentration of interleukin (IL) 2 and interferon-γ(IFN-γ) in supernatants of spleen lymphocyte were measured by enzyme-linked immunosorbent assay (ELISA). Results (1) BTLA gene expression was gradually increased after tumor cells inoculation. The highest expression level was 2. 83 + 0. 35 at 14th day, which had statistical significance difference with the 7th day expression of 1.66±0. 25 (P < 0. 05). While HVEM mRNA expression did not change significantly (P > 0. 05). The 7th and 14th day after TC-1 cells inoculation, the average fluorescence intensity of BTLA expression on the surface of tumor infiltrating lymphocytes was 33.5 and 51.8, respectively, in which there was statistically significant difference (P <0. 05); while the difference of HVEM expression was not statistically significant (57. 2 vs 49. 3 ,P >0. 05). (2)The 28th day after inoculation, tumor inhibition rate of HSP70 + psBTLA group was 88%, which was significantly higher than other treatment groups (P <0. 05). The 28th day after TC-1 cells inoculation, combination therapy not only promoted IFN-γ and IL-2 gene (3. 12 + 0.71,3.20 + 0. 62)expression but also reduced transforming growth factor-β (TGF-β), Foxp3 and IL-10 expression (0. 25±0. 03,0. 19 +0. 03,0. 31 +0. 04;P <0. 05). It also promoted CD8+ T lymphocyte infiltration(52 +6)/high power field, cytotoxicity (65.5±2.4) %, proliferation (15.0 × 103 cpm) and cytokine IL-2 , IFN-γsecretion(824±51), (1096±112) pg/ml, which were all significantly higher than other groups (P <0. 05). Conclusion The effect of immunotherapy on tumor can be augmented by the combination of psBTLA which expresses extracellular domain of BTLA and HSP70-TC-1 tumor antigen peptide complex,which could improve the expression of the related immunoregulatory genes to establish a much better microenvironment in favor of anti-tumor immune response against the mice model of the cervix carcinoma.

Objective:To explore the situation of insomnia, fatigue, depression, anxiety and cognitive impairment in adolescents with different characteristics, and the chain mediating effect of fatigue, depression and anxiety on insomnia and cognitive impairment.Methods:The general demographic data of 6 014 adolescents were collected.Insomnia severity index (ISI), the multidimensional fatigue inventory (MFI-20), patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7) and perceived deficits questionnaire-depression(PDQ-D) were used to compare the insomnia, fatigue, depression, anxiety and cognitive impairment of adolescents with different characteristics.Spearman correlation analysis was conducted by SPSS 20.0 software.The significance of mediating effect was tested by deviation corrected nonparametric percentile Bootstrap method using SPSS macro program PROCESS.Results:The detection rates of insomnia, fatigue, depression, anxiety and cognitive impairment were different in adolescents with different genders, grades and academic achievements.Cognitive impairment was significantly positively correlated with insomnia ( r=0.654, P<0.01), fatigue ( r=0.476, P<0.01), depression ( r=0.677, P<0.01), anxiety ( r=0.655, P<0.01), which was suitable for mediating effect test.Fatigue, depression and anxiety in adolescents had a chain mediating effect between insomnia and cognitive impairment.Insomnia indirectly affects cognition by affecting fatigue and depressive symptoms.The intermediary effect value was 1.253, the effect amount was 55.60%, and the total effect was 2.254.Insomnia indirectly affects cognition by affecting fatigue and anxiety symptoms.The intermediary effect value was 1.161, the effect amount was 51.50%, and the total effect was 2.254. Conclusion:Insomnia can not only directly affect their cognitive impairment, but also indirectly affect their cognitive impairment through the chain mediation of fatigue, depression and anxiety of adolescents.

Objective To explore the mediating effect of self-hate between adverse childhood experiences and depression,anxiety,and suicide risk in adolescents.Methods In Juxian county,Rizhao,Shangdong Province,a cross-sectional survey was conducted in 5 junior high schools and high schools using questionnaires.A total of 6838 valid questionnaires were collected.The assessment included a self-designed general information questionnaire,patient health questionnaire-9(PHQ-9),generalized anxiety disorder-7(GAD-7),the mini-international neuropsychiatric interview 5.0 suicide module,revised adverse childhood experience questionnaire(ACEQ-R),and self-hate scale(SHS)to evaluate relevant content.Results The detection rates of depression,anxiety,and suicide risk were significantly higher in girls(P<0.001)and in senior high school students(P<0.001).Adolescents with depression,anxiety,and suicide risk exhibited higher scores for adverse childhood experiences and self-hate compared to those without these conditions(P<0.001).Adverse childhood experiences indirectly predicted depression through self-hate with an indirect effect size of 0.1488,accounting for 60.86% of the total effect(P<0.001).Similarly,adverse childhood experiences indirectly predicted anxiety through self-hate with an indirect effect size of 0.1524,accounting for 62.87% of the total effect(P<0.001).Furthermore,adverse childhood experiences indirectly predicted the risk of suicide through self-hate with an indirect effect size of 0.0485,accounting for 49.44% of the total effect(P<0.001).Conclusions Adverse childhood experiences have predictive effects on depression,anxiety and suicide risk in adolescents,and self-hate plays a mediating role on depression,anxiety and suicide risk in adolescents.

Objective:To construct an evaluation the index system of entrustable professional activities for resident training doctors in psychiatric department,and to provide reference for formulating training strategies and assessment standards.Entrustable professional activities refers to the ability of trainees to perform and complete spe-cific clinical tasks independently after they have been trusted.Methods:Through documental analysis and semi-structured interviews,the item database of entrustable professional activities for psychiatric resident training physi-cians was established.Delphi consultation was conducted among 63 experts in the field of psychiatry from 7 national resident training bases and 3 medical colleges in China.Indicators were comprehensively screened and sorted out,and indicators at all levels and their weights were determined by the analytic hierarchy process.Results:A hierarchi-cal evaluation index system of entrustable professional activities for psychiatric resident training doctors was con-structed,including 4 first-level indicators,17 second-level indicators and 68 third-level indicators.The weights of the first-level,second-level and third-level indicators were determined.Conclusion:The evaluation index system of en-trustable professional activities is comprehensive and systematic,which is suitable for clinical work and convenient for practical application.It could provide quantitative standards for the assessment of psychiatric residents and pro-mote the improvement of training quality.

Objective:To investigate the clinical characteristics of E. coli peritoneal dialysis-associated peritonitis (PDAP) and the risk factors for its occurrence and treatment failure.Methods:The clinical data of patients with episodes of PDAP in four general hospitals in Jilin Province from 2013 to 2019 were retrospectively reviewed. According to the pathogenic bacteria, the patients were divided into E. coli and non- E. coli groups. The incidence of E. coli PDAP in the last seven years was calculated and the clinical characteristics were compared between two PDAP groups. Logistic regression was used to analyze the risk factors for the occurrence and treatment failure of E. coli PDAP. Results:A total of 693 PDAP episodes/cases were enrolled in this study, including 100 episodes/cases in the E. coli group and 593 episodes/cases in the non- E. coli group. The incidence rate of E. coli PDAP in the four hospitals showed a decreasing trend during 2013 to 2019. Compared with the non-E.coli group, the proportion of diabetic patients and the average blood albumin levels in the E. coli group were lower ( χ2=5.006, Z=-2.992, P<0.05), while the proportion of refractory peritonitis was higher, and the duration of antibiotic therapy was longer ( χ2=6.350, Z=-2.779, P<0.05). Multivariate Logistic regression analysis showed that history of PDAP ( OR=1.577, 95% CI: 1.015-2.448) and low baseline serum albumin level ( OR=0.958, 95% CI: 0.923-0.995) were independent risk factors for the development of E. coli PDAP, while concomitant diabetes was an independent protective factor for E. coli PDAP ( OR=0.538, 95% CI: 0.330-0.876). Moreover, long-term dialysis was an independent risk factor for treatment failure of E. coli PDAP ( OR=1.047, 95% CI: 1.018-1.076). Conclusion:The incidence rate of E. coli PDAP in study institutions has declined in the past 7 years, but the rate of refractory PDAP is still high. The history of PDAP and low blood albumin level are independent risk factors for the occurrence of E. coli PDAP, while concomitant diabetes is an independent protective factor for the occurrence of E. coli PDAP. Long-term dialysis is an independent risk factor for treatment failure of E. coli PDAP.

Objective:To investigate the clinicopathological and molecular genetic characteristics of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) with myxoid-like morphology, and to distinguish them from myxofibrosarcoma (MFS) with similar morphology.Methods:Twenty-nine cases of myxoid-like liposarcoma and 5 cases of MFS were collected from Henan Provincial People′s Hospital, Zhengzhou, China and the First Medical Center of PLA General Hospital, Beijing, China from January 2015 to March 2023. Relevant markers were detected using immunohistochemistry and fluorescence in situ hybridization (FISH). The literature was also reviewed.Results:There were 24 males and 10 females, with ages ranging from 41 to 73 years. The tumor sites included retroperitoneum ( n=17), abdomen ( n=9), lower limbs ( n=5), scrotum ( n=1), upper limb ( n=1) and axilla ( n=1). WDLPS was commonly seen as lipomatoid type (12 cases), while the dedifferentiated components of DDLPS included low-grade (13 cases) and high-grade (2 cases) morphology, with low-high grade myxofibrosarcoma, dermatofibrosarcoma protuberans, and low-grade fibrosarcoma structures. Twenty-nine liposarcomas had various proportions of myxoid-like morphology, while 16 showed various degrees of tumor necrosis. The myxoid-like component showed myxoid pleomorphic liposarcoma (MLPS)-like morphology, lobulated growth, characteristic slender, ramified capillary network,"chicken claw-like"morphology, mucus-rich stroma and lung edema-like morphology. Tumor cells were spindle and oval, with many variable vacuolar lipoblasts. MDM2 gene amplification was detected using FISH and present in all tested cases (29/29). DDIT3 break-apart mutation was not detected, but its cluster amplification was present (24/29). Among the MFS cases, one showed cluster amplification (1/5), but no cases showed break-apart or amplification of MDM2 gene. Conclusions:WDLPS/DDLPS with myxoid-like morphology is most commonly seen in the retroperitoneum and abdominal cavity and mostly harbors DDIT3 break-apart probe amplification, while this amplification is not specific to liposarcoma. For core biopsy specimens or very rare tumors in the limbs, when histology has mucinous stroma and MLPS-like morphology, misdiagnosis of MLPS or other non-lipomatous neoplasms with myxoid morphology should be avoided.

Objective To evaluate the efficacy of Budesonide/formoterol to control asthma under real-life conditions.Methods A muhi-center, open label, non-interventional study was conducted.Asthma control after 12 week therapy with Budesonide/formoterol was assessed by Asthma Control Questionnaire (ACQ) and modified Asthma Control Questionnaire (ACQ5).Results A total of 360 asthma patients were recruited,including 228 adult patients and 132 child patients.After 12 weeks' therapy,all the patients' medium value of ACQ was decreased significantly from 2.03 (adults 2.20, children 1.74) at baseline to 0.60 (adults 0.78, children 0.29) (P < 0.0001), and the medium value of ACQ5 was also decreased significantly from 2.4 (adults 2.24, children 1.76) at baseline to 0.47 (adults 0.62, children 0.20) (P < 0.0001).Conclusion Budesonide/formoterol is effective in asthma treatment, by which most asthma patients obtain and maintain clineal control.