Objective: To explore the therapeutic mechanism of puerarin in treating rheumatoid arthritis (RA) rats based on the serine/tyrosine protein kinase B (AKT)-phosphorylated forkhead box protein O1 (FOXO1)-interleukin-9 (AKT-FOXO1-IL-9) signaling pathway. Methods : 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . 36 rats were randomly divided into a blank group , a model group , a positive control group , and low , medium , and high dose groups of puerarin. Except for the blank group , the other groups were induced with type Ⅱ collagen to establish a RA rat model. After successful modeling , different doses of puerarin and methotrexate were given to treat the rats. The body mass and toe thickness of the rats were measured , and biochemical indicators of rat blood rheology were detected. X-ray was used to observe changes in rat joint morphology. Safranin green staining were used to observe the pathology of rat joint tissue. ELISA was used to detect the levels of IL-9 and rheumatoid factors in rat serum , and Western blot was used to detect changes in levels of AKT and FOXO1 . Results: Compared with the blank group , the model group had the lowest toe thickness , and X-ray images showed more obvious segmental stenosis and more severe marginal bone invasion ; scaly like changes appeared at the edges of joints stained with safranin green , accompanied by the exudation of inflammatory cells and increased proliferation and secretion of chondrocytes ; the expression levels of inflammatory factors IL-9 and rheumatoid factors were the highest , and the expression levels of AKT and FOXO1 proteins were the highest (P < 0. 05) . Compared with the model group , the toe thickness of rats treated with different doses of puerarin decreased ; X-ray images showed that the puerarin treatment group of rats showed improvement in plantar joint stenosis and marginal bone invasion ; the results of safranin green staining showed that after treatment with different doses of puerarin , the infiltration of inflammatory cells decreased , and the expression levels of inflammatory factor IL-9 , rheumatoid factors , AKT , and FOXO1 proteins decreased significantly ( P < 0. 05 ) , with the high-dose puerarin group showing the most significant difference. Compared with the high-dose puerarin group , the positive control group showed a significant decrease in the above results and statistical differences (P < 0. 05) . Conclusion Puerarin has a good therapeutic effect on rats with RA by inhibiting the AKT-FOXO1-IL-9 pathway. The high-dose puerarin group (60 mg/kg) has the best therapeutic effect and the results show a dose-response relationship.

Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade (ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified; some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration (FDA) for clinical treatment. However, limited responses and immune-related adverse events (irAEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasms/drug therapy* ; Immunotherapy/methods* ; Animals

Objective To explore the risk factors for portal vein thrombosis(PVT)in patients with cirrhosis in the decompensated stage and construct a risk prediction model for PVT so as to improve the early diagnosis rate of decompensated liver cirrhosis PVT.Methods The clinical data of patients with cirrhosis in the decompensated stage admitted to Department of Gastroenterology,The First Affiliated Hospital of Xi'an Jiaotong University between June 2018 and June 2023 were collected and divided into cirrhosis PVT group(n=135)and cirrhosis non-PVT group(n=225)according to whether or not portal vein thrombosis was formed.We made a univariate analysis of the general data,laboratory indexes,liver function scores and imaging findings of the patients in the two groups,and indexes with statistically significant differences were included in binary Logistic regression for multifactorial analysis to screen out independent risk factors.A predictive model of binary Logistic regression was established based on the independent risk factors.The clinical data of the validation set were incorporated into the model,the accuracy of the prediction model was evaluated by receiver operating curve(ROC),and the practicability of the model was evaluated by consistency curve to complete the validation and evaluation of the constructed prediction model.Internal stability of the model was verified with Bootstrap method.Finally,R software(4.3.1)was used to draw a nomogram of the prediction model to visualize the model.Results Univariate analysis revealed statistically significant differences between patients in the PVT and non-PVT groups in the following five aspects:history of splenectomy,history of endoscopic varicose vein treatment,portal vein diameter,and neutrophil-to-lymphocyte ratio(P＜0.05).Binary Logistics regression analysis showed that a history of splenectomy(P=0.002,OR=3.012,95％CI:1.500-6.047),a history of endoscopic varicose vein treatment(P=0.001,OR=2.276,95％CI:1.400-3.698),widening of portal vein diameter(P=0.007,OR=1.942,95％CI:1.202-3.136),increased neutrophil-to-lymphocyte ratio(P=0.009,OR=1.886,95％CI:1.170-3.041),and elevated D-dimer(P＜0.001,OR=3.725,95％CI:2.149-6.485)were independent risk factors for the formation of portal vein thrombosis in patients with cirrhosis in the decompensated stage of cirrhosis chemically presented(P＜0.05).The area under the ROC curve of the predictive model and the model after internal validation was 0.760 and 0.7494,respectively.The model still had good prediction ability and accuracy in the verification set.Conclusion A history of splenectomy,history of endoscopic varicose vein treatment,widening of portal vein diameter,increased neutrophil-to-lymphocyte ratio,and elevated D-dimer concentration are independent risk factors for the formation of portal vein thrombosis in patients with decompensated cirrhosis.The Logistic prediction model and visual nomogram constructed based on the above independent risk factors have a good ability to predict the occurrence of PVT in patients with decompensated cirrhosis and have important clinical guiding significance for early screening patients with PVT in decompensated cirrhosis.

Objective:To investigate the role of telomere length in the causal effects of immune-mediated diseases on liver fibrosis.Methods:Genome-wide association study (GWAS) data were extracted from open GWAS (https: //gwas.mrcieu.ac.uk) for a two-sample Mendelian randomization (MR) analysis. Five immune-mediated autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, primary biliary cholangitis, and Crohn′s disease) individually and collectively were included as exposure factors, telomere length as a mediator, and liver fibrosis as the outcome. The Wald ratio and inverse variance weighted (IVW) methods were performed to assess causal effects. The MR-Egger intercept test was adopted to evaluate the level of horizontal pleiotropy. Multivariable MR was employed to quantify the proportion of the effect of immune-mediated diseases on liver fibrosis mediated by telomere length. And sensitivity analyses were performed to assess the robustness of the results.Results:The results of IVW analysis revealed that the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, primary biliary cholangitis, and Crohn′s disease were causally related to the high risk of liver fibrosis, and the OR were 1.63 (95% confidence intervals (95% CI): 1.33 to 2.10), 1.28 (95% CI: 1.14 to 1.43), 1.34 (95% CI: 1.02 to 1.74), 1.36 (95% CI: 1.27 to 1.47), 1.37 (95% CI: 1.23 to 1.52), and 1.52 (95% CI: 1.15 to 2.01), respectively ( P<0.001, <0.001, =0.032, <0.001, <0.001, =0.003). Horizontal pleiotropy was detected in the association between Crohn′s disease and liver fibrosis (MR-Egger intercept test, P=0.025).The results of multivariable MR indicated that telomere length acted as a mediating factor in the causal relationship between liver fibrosis and the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cholangitis ( OR=2.24, 95% CI: 1.41 to 3.56; OR=1.78, 95% CI: 1.03 to 3.06; OR=2.11, 95% CI: 1.31 to 3.40; OR=2.01, 95% CI: 1.06 to 3.80; P<0.001, =0.038, =0.002, =0.032, respectively ). Conclusion:The causal effects of the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, and primary biliary cholangitis on liver fibrosis are mediated by telomere length.

Objective:To explore the relationship between Metabolic Score of Visceral Fat(METS-VF)and new-onset stroke in Chinese middle-aged and elderly individuals aged ≥45 years.Methods:This study is a prospective cohort study that included 3 311 participants from the China Health and Retirement Longitudinal Study(CHARLS)database, with new-onset stroke as the primary endpoint.The association between METS-VF and new-onset stroke was evaluated by Cox proportional hazards model, subgroup analysis and restricted cubic spline(RCS)analysis.Additionally, mediation analysis was used to assess the mediating effect of remnant cholesterol(RC)on the association between METS-VF and stroke.Results:During the 9-year follow-up period, 138(4.2%)middle-aged and elderly individuals experienced stroke.Compared with the lowest quartile group of METS-VF, the fully adjusted HR and 95% CI of new-onset stroke in the second, third and fourth quartiles were 1.78(1.03-3.08), 1.96(1.12-3.44)and 2.19(1.17-4.10), respectively with a statistically significant trend( P for trend<0.05). Mediation analysis indicated that the indirect effect mediated by RC accounted for 13.51% of the association between METS-VF and new-onset stroke( P=0.03), and RCS analysis revealed a linear dose-response relationship between METS-VF and stroke( P for overall=0.022, P for non-linearity=0.198); The results of the subgroup analyses were consistent with the main analyses( P interaction>0.05). Conclusions:METS-VF may serve as a potential biomarker in risk stratification of stroke, with RC partially mediating this association.

Objective:To analyze the epidemiological characteristics and influencing factors of single-cigarette use and dual cigarette-cigar use in China.Methods:This study was a cross-sectional study that selected 85 638 urban and rural residents who met the inclusion criteria from the 2018 China Health Literacy Survey as research subjects. An analysis was conducted on 21 849 users of cigarettes and cigars among them. Due to the small number of individuals who exclusively used cigars (247 cases), the research subjects were divided into two categories: exclusive cigarette users and dual users of cigarettes and cigars. The groups were categorized by age (18-34 years, 35-54 years, ≥55 years), gender (male, female), education level (primary school and below, junior high school and high school, university and above) and annual household income (<20 000 yuan, 20 000-<80 000 yuan, ≥80 000 yuan) to compare the tobacco usage rate and conduct subgroup analyses for each subgroup. Multivariate logistic regression analysis was employed, incorporating general demographic characteristic information to explore the influencing factors of exclusive cigarette use and dual use of cigarettes and cigars, respectively.Results:The rate of exclusive cigarette use in our country was 24.3%, while the dual use rate of cigarettes and cigars was 0.9%. The exclusive cigarette use rate and the dual use rate of cigarettes and cigars among males were significantly higher than those among females (48.25% vs 2.48%, and 1.84% vs 0.06%) (both P<0.001). For males, the high-risk factors for exclusive cigarette use included living in urban areas ( OR: 1.37, 95% CI: 1.23-1.54), being Han ethnicity ( OR: 1.73, 95% CI: 1.51-1.98), and having an annual household income ≥20 000 yuan ( OR: 1.54, 95% CI: 1.38-1.82) while having a junior high school education or higher was a protective factor ( OR: 0.68, 95% CI: 0.52-0.90). Age≥35 years ( OR: 3.36, 95% CI: 2.62-4.32) and having a junior high school education or higher ( OR: 1.30, 95% CI: 1.02-1.67) were risk factors for dual use of cigarettes and cigars in males. Among females, living in urban areas ( OR: 1.53, 95% CI: 1.19-1.97) and being Han ethnicity ( OR: 5.96, 95% CI: 4.47-7.96) were risk factors for exclusive cigarette use, while having a university education or higher was a protective factor ( OR: 0.28, 95% CI: 0.18-0.42). However, for female dual use of cigarettes and cigars, no significant effects were observed for any demographic characteristics. Conclusions:The use rate of cigarettes alone in China is significantly higher than that of cigarette-cigar dual use, and the rates of cigarette use alone and cigarette-cigar dual use in men are significantly higher than those in women. Tobacco use is being affected by sociodemographic factors, among which place of residence, ethnicity and education level are the main influencing factors of cigarette use alone, and gender, age and education level are the main influencing factors of cigarette-cigar dual use.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

Objective:To adapt the English version of exteroceptive body awareness questionnaire (EBA-q) into Chinese, and evaluate its reliability and validity in college students.Methods:English version EBA-q was translated and culturally adapted into Chinese, and the tests were administered from October to December 2024, with valid data collected from 1 071 college students. Item analysis, exploratory factor analysis, confirmatory factor analysis, criterion-related validity analysis, and reliability analysis were conducted by SPSS 23.0 and Mplus 8.3 softwares.Results:(1) The Chinese version of EBA-q contained seventeen items across five factors: visual awareness, tactile awareness, body coordination, awareness of body changes and awareness of clothing fit. The five-factor measurement model fitted the data well ( χ2/ df=2.24, CFI=0.95, TLI=0.94, RMSEA=0.05, SRMR=0.06). (2) The EBA-q scores were positively correlated with the scores of noticing, body listening, public self-consciousness, and private self-consciousness ( r=0.46, 0.36, 0.09, 0.25, all P<0.01). (3)The Cronbach's α coefficient, split-half reliability and test-retest reliability of the Chinese version of EBA-q were 0.79, 0.85 and 0.77, respectively(all P<0.01). Conclusion:The Chinese version of the EBA-q has demonstrated good reliability in assessing external body awareness among college students, but its validity requires further verification.

Objective:To explore the relationship between life events, anxiety, depression, and behavior problems in adolescents.Methods:From September to October 2022, the cluster sampling method was used to select 5 341 adolescents from 4 middle schools in Xinxiang urban area.The subjects and their parents were investigated by the adolescent self-rating life events check list (ASLEC), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9), and child behavior checklist (CBCL). SPSS 27.0 software was used for Spearman correlation analysis, and AMOS 28.0 software was used to construct the structural equation model.Results:The scores of anxiety, depression, and behavioral problems were 1 (0, 4), 1 (0, 4), and 3 (0, 10). The total score of life events was 5 (1, 13), and the dimensions scored as follows: interpersonal conflict 1 (0, 4), academic pressure 2 (0, 5), punishment 0 (0, 2), loss 0 (0, 0), health and adaptation problem 0 (0, 1), and others 0 (0, 2). There were positive correlations between life events and its dimensions, depression, anxiety and behavioral problems ( r=0.28-0.69, all P<0.01). In the overall population, anxiety and depression played parallel mediating roles in the impact of life events on behavior problems. Life events could positively predict anxiety ( β=0.68, P<0.01), and anxiety could positively predict behavior problems ( β=0.04, P=0.02). Life events could positively predict depression ( β=0.77, P<0.01), and depression could positively predict behavior problems ( β=0.18, P<0.01). The standardized total effect size of the impact of life events on behavioral problems was 0.622 (95% CI=0.564-0.675). The standardized direct effect size and indirect effect size were 0.460 (95% CI=0.374-0.539) and 0.162 (95% CI=0.108-0.218), accounting for 74.0% and 26.0%of the total effect, respectively. After stratification by gender, the results for male adolescents were consistent with the overall population, while the mediating effect of anxiety was not significant in the female adolescents. Conclusion:Life events can lead to anxiety and depression in adolescents, thereby increasing the risk of behavior problems.

Objective:To adapt the English version of exteroceptive body awareness questionnaire (EBA-q) into Chinese, and evaluate its reliability and validity in college students.Methods:English version EBA-q was translated and culturally adapted into Chinese, and the tests were administered from October to December 2024, with valid data collected from 1 071 college students. Item analysis, exploratory factor analysis, confirmatory factor analysis, criterion-related validity analysis, and reliability analysis were conducted by SPSS 23.0 and Mplus 8.3 softwares.Results:(1) The Chinese version of EBA-q contained seventeen items across five factors: visual awareness, tactile awareness, body coordination, awareness of body changes and awareness of clothing fit. The five-factor measurement model fitted the data well ( χ2/ df=2.24, CFI=0.95, TLI=0.94, RMSEA=0.05, SRMR=0.06). (2) The EBA-q scores were positively correlated with the scores of noticing, body listening, public self-consciousness, and private self-consciousness ( r=0.46, 0.36, 0.09, 0.25, all P<0.01). (3)The Cronbach's α coefficient, split-half reliability and test-retest reliability of the Chinese version of EBA-q were 0.79, 0.85 and 0.77, respectively(all P<0.01). Conclusion:The Chinese version of the EBA-q has demonstrated good reliability in assessing external body awareness among college students, but its validity requires further verification.