Objective: To understand the impact of childhood trauma on psychological distress among upper grade elemetary school students, and to explore the mediating role of leisure activities in the relationship, so as to provide a basis for developing mental health intervention strategies. Methods: From August to November 2024, a combination of convenience sampling and stratified cluster random sampling was employed to recruit 1 373 fourth to sixth grade students from four primary schools in Harbin. The Childhood Trauma Questionnaire(CTQ), a self designed leisure activity scale (including active and passive leisure activities), and the Kessler Psychological Distress Scale (K10) were used to assess childhood trauma experiences, leisure activities, and levels of psychological distress. Spearman correlation analysis and linear regression analysis were conducted to explore the relationships among childhood trauma, leisure types, leisure time, and psychological distress. Based on the mediation analysis framework proposed by Hayes (Model 4), the mediating role of leisure types in the relationship between childhood trauma and psychological distress was examined. Results: Totally 19.1% of the upper elemetary school students exhibited psychological distress, while 30.2% had experienced childhood trauma. During school days, 64.6% of the students were reported of having leisure time concentrated between 1 and 5 hours per day, whereas 67.4% reported leisure time exceeding 5 hours per day on weekends. After controlling for potential demographic confounders such as gender, grade, ethnicity, household registration, being an only child, parents educational level, co residence, and whether parents are first time married,linear regression analysis showed that childhood trauma experience had positive predictive effect on psychological distress in upper primary school students( β =0.20, P <0.01). Leisure time showed no statistically significant association with psychological distress, both on school days ( β =-0.58 to -0.56) and weekends ( β =0.26- 0.98 )(all P >0.05). Active leisure activities were negatively associated with psychological distress ( β =-0.20), while passive leisure activities were positively associated with psychological distress ( β =0.29)(both P <0.01). Leisure type partially mediated the relationship between childhood trauma and psychological distress, accounting for 11.7% of the indirect effect. Conclusion Childhood trauma experiences positively predict psychological distress in upper elementary school students, and affect psychological distress through active leisure and passive leisure.

ObjectiveTo investigate the therapeutic effect of wall-broken ganoderma lucidum spore powder （GLS） on a mouse model of hepatocellular carcinoma and to explore its underlying mechanism. MethodsFifty 2-week-old C57BL/6J mice were divided into a control group， a model group and low， medium and high-dose GLS groups（0.25， 0.5， 1.0 g/kg ）， with 10 mice in each group. A DEN/CCL₄ mouse hepatocellular carcinoma model was established， and GLS was administered by gavage starting from the 8th week， once a day for 14 weeks. At the end of the final administration， the number of liver nodules was observed ， and the serum alpha-fetoprotein （AFP） was detected using enzyme-linked immunosorbent assay. The content of catalase （CAT） in serum and liver tissue was determined by ammonium molybdate method. The content of reduced glutathione （GSH） in serum and liver tissue was measured by microplate assay. The content of glutathione peroxidase （GSH-PX） in serum and liver tissue was detected by colorimetric method. Immunohistochemistry （IHC-P） was employed to detect the protein expression of proliferating cell nuclear antigen （PCNA）. R eal-time fluorescence quantitative polymerase chain reaction was utilized to detect the relative expression of nuclear factor E2-related factor 2 （Nrf2）， Kelch-like epichlorohydrin-associated protein 1 （Keap1）， NAD（P）H quinone oxidoreductase 1 （Nqo1）， heme oxygenase-1 （Ho-1） and glutamate cysteine ligase catalytic subunit （Gclc） mRNA. ResultsCompared with the control group， the content of serum AFP were significantly higher in the model group （P<0.01）， while the contents of CAT， GSH and GSH-PX in liver and serum were significantly lower in the model group （P<0.01）. The relative expression of Keap1 and Nqo1 mRNA was significantly higher （P<0.01）， the relative expression of Nrf2， Ho-1， Gclc mRNA relative expression was significantly lower （P<0.01）， and the positive expression rate of PCNA was significantly higher （P<0.01）. Compared with the model group， the total number of liver nodules and content of serum AFP in the administered group were significantly lower （P<0.01）， and the contents of CAT， GSH， and GSH-PX in the liver and serum of mice significantly increased （P<0.05 or P<0.01）. The expression of Keap1 and Nqo1 mRNA significantly decreased （P<0.05）. The expression of Nrf2， Ho-1 and Gclc mRNA significantly increased （P<0.05）， and positive expression rate of PCNA significantly decreased （P<0.01）. ConclusionGLS has a significant protective effect on DEN/CCL4 -induced mouse hepatocellular carcinoma model， and the mechanism of action is related to the regulation of oxidative stress in mouse liver.

Objective: To explore the impact of sleep quality, experience of childhood maltreatment, and their interaction on depressive symptoms among middle school students, so as to provide the reference for early intervention of depressive symptoms among middle school students. Methods: From September to December 2023, a questionnaire survey was conducted among 1 231 students from two secondary schools in Harbin, Heilongjiang Province by a convenient sampling method. The survey included general demographic information, Childhood Trauma Questionnaire Short Form, Pittsburgh Sleep Quality Index and Short Version of Center for Epidemiological Studies Depression Scale. The Chi square test was used to analyze the differences in depressive symptom, sleep quality and childhood maltreatment among students with different demographic characteristics. Correlation analysis was conducted using Logistic regression, and interaction analysis was performed by both additive and multiplicative interaction models. Results: The detection rate of depressive symptoms among middle school students was 22.7%, and the rate for high school students (35.2%) was significantly higher than that for middle school students (17.0%) ( χ 2=50.35, P <0.01). The detection rates of depressive symptoms among middle school students with a history of childhood maltreatment and poor sleep quality were 45.8% and 44.0%, respectively. Multivariate Logistic regression analysis showed that compared to students without a history of childhood maltreatment, students with a history of childhood maltreatment had a higher risk of depressive symptoms ( OR =4.49，95% CI =3.31~ 6.09 , P <0.01);students with poor sleep quality had a higher risk of depressive symptoms than students with good sleep quality ( OR = 5.99，95% CI =4.37~8.22, P <0.01).The interaction results showed that the presence of childhood maltreatment and poor sleep quality had an additive interaction on the occurrence of depression in middle school students. Compared with students without childhood maltreatment and having good sleep quality, students with childhood maltreatment and poor sleep quality had a 22.49 times higher risk of developing depression ( OR =22.49，95% CI =14.22~35.59, P <0.01). Conclusion Depressive symptoms among middle school students are associated with childhood maltreatment and poor sleep quality, and there is an additive interaction between childhood maltreatment and poor sleep quality on the impact of depressive symptoms.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

Immune checkpoint inhibitors(ICIs)represent the most widely used immunotherapeutic approach for antitumor treatment,yet the understanding of their associated hepatotoxicity remains incomplete.This article delves into and analyzes the similarities and differences among the management guidelines on ICI-related hepatotoxicity issued by the Chinese Society of Clinical Oncology(CSCO),the National Comprehensive Cancer Network(NCCN)of the United States,and the American Society of Clinical Oncology(ASCO),aiming to provide a more comprehensive management strategy for clinical practice.By reviewing and analyzing the latest guidelines,this study compares the differences and similarities in the diagnosis,assessment,grading criteria,and treatment strategies for ICI-related liver toxicity among these guidelines.The definitions and diagnostic criteria for ICI-related liver toxicity are generally consistent across different guidelines,primarily relying on the elevated levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),bilirubin,and alkaline phosphatase(ALP)for grading.Notably,the ASCO guidelines place a stronger emphasis on the assessment of symptoms of hepatic dysfunction.In terms of treatment strategies,all guidelines recommend using corticosteroids or immunosuppressants based on the toxicity grade.However,there are discrepancies in management strategies among the guidelines.Clinicians should tailor management strategies by considering the specific conditions of patients and integrating the recommendations from various guidelines.Additionally,given the current inadequate understanding of ICI-induced hepatotoxicity primarily manifested as cirrhosis in the existing guidelines,it is imperative to continuously update and refine these management guidelines as research progresses and clinical experience accumulates.

Objective:To investigate the sex difference and symptom correlation of pituitary-thyroid axis and pituitary-adrenal axis function in patients with remitted schizophrenia.Methods:Using cross-sectional study method,243 patients with remitted schizophrenia at Changning District Mental Health Center of Shanghai from January 2019 to September 2021(schizophrenia group)were selected,and healthy individuals who underwent physical examinations during the same period(healthy control group)were also selected.The demographic data and HPT axis,HPA axis neuroendocrine indicators[serum thyroid stimulating hormone(TSH),free triiodothyronine(FT3),free thyroid hormone(FT4),triiodothyronine(TT3),thyroid hormone(TT4),adrenocorticotropic hormone(ACTH),and cortisol(COR)]between healthy control group and schizophrenia group were compared.Gender differences in HPT axis and HPA axis in schizophrenia patients were compared.The correlation between neuroendocrine indicators and gender,disease duration,positive and negative symptom scale(PANSS)scores in patients with schizophrenia were analyzed by linear regression method.Using stratified multiple linear regression,laboratory measured variables and age were included as predictive factors in the model to construct a regression prediction model for hormone levels between schizophrenia and healthy control group,as well as subgroups of schizophrenia gender.Generate receiver operating characteristic(ROC)curves based on the probability values of predictive factors,and determine the predictive value of the logistic regression model using the area under the curve(AUC).Results:TT3,TSH,TT4 in schizophrenia group were lower than those in the healthy control group(P＜0.05),while ACTH and COR were higher than those in the healthy control group(P＜0.05).There was a statistically significant difference in the negative symptom scores,TSH,TT3,FT3,ACTH,and COR levels between the female schizophrenia group and male schizophrenia group(P＜0.05).PANSS,total score of general psychopathology score were positively correlated with COR level,negative symptom score was negatively correlated with FT3 levels(all P＜0.05),but there was no linear relationship among the three(absolute value of r＜0.3).ROC curve results showed that,the schizophrenia hormone level model had good discrimination accuracy,with AUC=0.872(95％confidence interval 0.841-0.904),the optimal threshold(Yoden index)=0.651.ROC curve shows that the male and female subgroups of schizophrenia models also have good discrimination accuracy,with AUC=0.794(95％confidence interval 0.737-0.850)and the optimal cutoff value(Yoden index)=0.495.Conclusion:The changes of active T4 in schizophrenia patients may be one of the possible causes of the chronic pathological changes of schizophrenia.The level of high-functioning T3 hormone is significantly lower in female patients than that in male patients.The hierarchical regression model provides good identification accuracy for remitted schizophrenia and gender subgroups.

This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20％to 0.91％,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100％compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.

OBJECTIVE: To analyze the distribution characteristics of glucose-6-phosphate-dehydrogenase (G6PD) mutations and their enzyme activity in newborns patients with G6PD deficiency in Guilin region. METHODS: From July 2022 to July 2024, umbilical cord blood samples from 4 554 newborns in Guilin were analyzed for G6PD mutations using fluorescence PCR melting curve analysis. Enzyme activity was detected in 4 467 cases using the rate assay. RESULTS: Among 4 467 newborns who underwent G6PD activity testing, 162 newborns (3.63%) were identified as G6PD-deficient, including 142 males (6.04%) and 20 females (0.94%), the prevalence of G6PD deficiency was significantly higher in males than in females (P < 0.001). Genetic analysis of 4 554 newborns detected G6PD mutations in 410 cases (9%), including 171 males (7.13%) and 239 females (11.09%), with a significantly higher mutation detection rate in females than in males (P < 0.001). A total of nine single mutations and four compound heterozygous mutations were identified. The most common mutations were c.1388G>A (33.66%), c.1376G>T (23.66%) and c.95A>G (16.34%). Among newborns who underwent both enzyme activity and genetic mutation testing, males with G6PD mutations had significantly lower enzyme activity than that of females with G6PD mutations(P < 0.001). Specifically, among newborns carrying the mutations c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T or c.871G>A, males consistently exhibited lower enzymatic activity than females with the same mutations (P < 0.001). Furthermore, in male G6PD-deficient newborns, the enzyme activity levels in those carrying c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T, or c.871G>A were lower than those in both the control group and the c.519C>T group (P < 0.05). CONCLUSION This study provides a comprehensive profile of G6PD deficiency incidence and mutation spectrum in the Guilin region. By analyzing enzyme activity and genetic mutation results, this study provides insights into potential intervention strategies and personalized management approaches for the prevention and treatment of neonatal G6PD deficiency in the region.
Humans ; Infant, Newborn ; Glucosephosphate Dehydrogenase Deficiency/epidemiology* ; Glucosephosphate Dehydrogenase/genetics* ; Female ; Male ; Mutation ; China/epidemiology*

BACKGROUND: It remains unclear whether sleep duration and physical activity (PA) trajectories in middle-aged and older adults are associated with different risks of cardiovascular diseases (CVDs). This study aimed to explore the trajectories of total sleep duration and PA among middle-aged and older Chinese adults and their impact on CVD risk. METHODS: This study was based on the China Health and Retirement Longitudinal Study. 12009 adults aged 45 years and older from five waves were included. CVD events were measured by self-reports of heart disease and stroke. We first used group-based trajectory modeling to identify total sleep duration and PA trajectories from 2011 to 2020, and then employed logistic regression models to analyze their risk for CVD. RESULTS: We identified three sleep duration and PA trajectories. The risk of heart disease increased by 33% (OR = 1.31, 95% CI: 1.12-1.53) for the short sleep duration trajectory (vs. moderate sleep duration trajectory), by 40% (OR = 1.40, 95% CI: 1.06-1.84) for the high decreasing PA trajectory, and by 20% (OR = 1.20, 95% CI: 1.01-1.42) for the low stable PA trajectory (vs. high stable PA trajectory), respectively. Similar results for stroke and CVD as the outcomes were also observed, but the higher risk of stroke in the high decreasing PA trajectory group was not statistically significant. The joint effects of sleep and PA showed lower risks of heart disease and stroke in trajectories with moderate or long sleep duration and high stable PA compared with short sleep duration and a low stable PA trajectory. CONCLUSIONS Short total sleep duration, high decreasing PA, and low stable PA trajectories could increase the risk of CVDs among middle-aged and older adults. Long-term moderate to long total sleep durations and high stable PA trajectories might be optimal for preventing CVDs.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies