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 effect of mitochondrial calcium uniporter （MCU） on the cytoskeleton of pancreatic ductal epithelial cells in a mouse model of acute pancreatitis （AP） induced by caerulein （CAE）， to analyze the role of MCU in the development of AP， and to provide a theoretical basis for clinical treatment. MethodsIn the in vivo experiment， wild-type male C57BL6/J mice， aged 4 weeks， were randomly divided into control group and AP group， with 6 mice in each group. The mice in the AP group were given intraperitoneal injection of CAE to establish a model of AP， and those in the control group were given intraperitoneal injection of an equal volume of normal saline. Serum and pancreatic tissue samples were collected after 24 hours of modeling. HE staining was used to observe pancreatic histopathological changes； Western Blot was used to measure the expression levels of MCU， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long chain family member 4 （ASCL4）； kits were used to measure the serum level of amylase. In the in vitro experiment， the human pancreatic ductal epithelial cell line HPDE6-C7 was co-cultured with CAE for 24 hours to establish an in vitro AP model， and the cells were divided into control group， CAE group， RR （an MCU activity inhibitor） group， CAE+RR group， Fer-1 （an ferroptosis inhibitor） group， CAE+Fer-1 group， Erastin （an ferroptosis inducer） group， and CAE+Erastin group. CCK-8 assay was used to observe the influence of different agents on cell viability； Western Blot was used to measure the expression levels of MCU， GPX4， and ASCL4； immunofluorescence assay was used to measure reactive oxygen species （ROS）， actin cytoskeleton， and monolayer permeability； kits were used to measure the concentrations of malondialdehyde （MDA）， glutathione （GSH）， Fe²⁺， and total iron. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for comparison between two groups. ResultsIn the in vivo experiment， compared with the control group， the AP group had significant increases in pancreatic histopathological score， the serum level of amylase， and the expression levels of MCU and ASCL4， as well as a significant reduction in the expression of GPX4 （all P<0.05）. In the in vitro experiment， compared with the control group， the CAE group had significant increases in the expression levels of MCU and ASCL4， a significant reduction in the expression of GPX4， and significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability， as well as a significant reduction in the concentration of GSH （all P<0.05）， with the presence of actin cytoskeleton disruption. Compared with the CAE group， the CAE+RR group had a significant increase in the expression level of GPX4， a significant reduction in the expression level of ASCL4， and significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Fer-1 group had significant reductions in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant increase in the concentration of GSH （all P<0.05）， with alleviation of actin cytoskeleton disruption. Compared with the CAE group， the CAE+Erastin group had significant increases in the concentrations of Fe²⁺， total iron， and MDA， the green fluorescence intensity of ROS， and monolayer permeability and a significant reduction in the concentration of GSH （all P<0.05）， with aggravation of actin cytoskeleton disruption. ConclusionDuring the onset of AP， MCU mediates oxidative stress-induced ferroptosis and leads to the disruption of the pancreatic ductal epithelial barrier， which may be one of the possible pathogeneses of AP.

Artificial intelligence （AI） and population pharmacokinetics （PPK） technologies have demonstrated significant potential in the personalized medication of immunosuppressants after organ transplantation, enabling precise prediction of drug dosages. This article provides a comprehensive review of the application status of AI and PPK in the individualized administration of immunosuppressants after organ transplantation， focuses on monitoring blood drug concentration， predicting efficacy/adverse reactions， and establishing individualized dosing models for organ transplant recipients after immunosuppressant administration， and analyzes and compares the application characteristics of different methods in different organ transplant patients as well as the integration and future development of AI and PPK technologies. AI and PPK technologies can not only significantly reduce the dependence on human resources， but also greatly improve the level of individualized treatment of immunosuppressants after organ transplantation， and reduce the discomfort and burden caused by frequent blood concentration monitoring to patients.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.

Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

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.

Objective To explore the prognostic value of plasma sST2 in the population of coronary heart disease(CHD)complicated with chronic kidney disease(CKD).Methods A total of 326 elderly patients with CHD or CKD undergoing physical examination in the Second Medical Center of Chinese PLA General Hospital from April 2021 to July 2022 were continuously enrolled,and according to whether having CHD or CKD,they were divided into a CHD-CKD comorbidity group(n=117),a CHD group(n=124),and a CKD group(n=85).Their baseline data were compared,and the plasma concentration of sST2 was detected using chemiluminescence assay.Multiple linear regression analysis was used to identify the relevant factors of sST2.Kaplan-Meier survival curve and Cox proportional hazards regression analyses were applied to determine the impact of plasma sST2 on all-cause mortality and major adverse cardiovascular events(MACE).Results There were significant differences among the three groups in terms of age,sST2 and NT-proBNP levels,Log(NT-proBNP),eGFR,ratios of hyperuricemia,cerebral infarction,tumors,and using anti-platelet drugs and statins,PR interval,LVEF,and TC,TG,HDL-C and Hb levels(P＜0.05,P＜0.01).Multiple linear regression analysis showed that the sST2 level was positively correlated with logNT-proBNP and negatively with Hb level in the comorbidity group(t=2.266,P=0.025;t=-2.235,P=0.021).Kaplan-Meier survival curve analysis indicated that during a median fol-low-up of 31.5(22.0,32.2)months,the comorbidity group had a lower survival rate than the two single-disease groups(P＜0.05,P＜0.01),and higher incidence of MACEs than the CKD group(P＜0.01).ROC curve analysis suggests that the AUC value of sST2 in predicting all-cause mor-tality in the comorbid group was 0.692.Cox proportional hazards regression model revealed that after adjustment for cofounders,sST2 was still an independent risk factor for all-cause mortality in the comorbid patients(HR=4.461,95％CI:1.640-8.399,P=0.024),although this prognos-tic value may be influenced by NT-proBNP.Conclusion sST2 can independently predict the risk of mortality in elderly patients with CHD-CKD comorbidity.

Objective:To evaluate the prevalence of hepatitis C virus (HCV) infection among patients attending a comprehensive tertiary hospital in Beijing and to pinpoint the key demographics for anti-HCV screening.Methods:A comprehensive retrospective analysis was undertaken, examining data from 631 424 patients who underwent anti-HCV testing between 2017 and 2023. Testing for anti-HCV was conducted using the Abbott i2000 fully automated chemiluminescent immunoassay analyzer. HCV nucleic acid testing was performed with the Roche Cobas AmpliPrep/Cobas TaqMan 96 fluorescent quantitative PCR system, while HCV genotyping was achieved through sequencing.Results:The positive rate of HCV antibodies demonstrated a gradual decline over the years, decreasing from 1.62% in 2017 to 1.01% in 2023. The overall positive rate stood at 1.36% (8 574/631 424), with a nucleic acid testing rate of 59.24% (5 079/8 574) and a nucleic acid positive rate of 34.28% (1 741/5 079). The majority of anti-HCV positive patients came from the department of hepatology (12.17%), followed by hepatobiliary surgery (3.03%), emergency medicine (1.68%), cardiovascular medicine (1.24%) and ophthalmology clinic (1.23%). Notably, the anti-HCV positive rate was significantly elevated in the ≥40 years old group compared to the <40 years old group, with statistical significance ( χ2=1 892.577, P=0.000). The highest anti-HCV positive rates were observed within the 60-69- and 80-99-years old brackets (both at 1.85%), while the peak HCV RNA positive rate was recorded in the 50-59 years old group (27.08%). Females exhibited a significantly higher positive rate (18.53%) than males (15.75%) ( χ2=8.066, P<0.01). When anti-HCV levels surpassed 9 S/CO, the HCV RNA positive rate was notably high, exceeding 38.97%. Intriguingly, at antibody levels ranging from 15 to 16 S/CO, the HCV RNA positive rate climbed to a maximum of 56.17%. Conclusions:This study has successfully identified the key populations for anti-HCV screening: Patients aged over 40, particularly female patients within the 50-69 age bracket; Patients in hepatology, hepatobiliary surgery, emergency medicine, cardiovascular medicine and ophthalmology departments.

Objective To investigate mortality risk factors and characterize pathogen distribution and antimicrobial resistance patterns in intensive care unit(ICU)patients with suspected infection following surgery.Methods A total of 65 hospitals in 16 provinces in China from July 1,2021,to December 31,2022.Clinical data were collected for surgical patients transferred to the ICU with suspected infection.Data included demographics[sex,age,underlying conditions(hypertension,diabetes,cardiovascular/cerebrovascular disease,hematologic disease)],surgical site,infection site,microbiological results with susceptibility testing,drug resistance and acute physiology and chronic health evaluationⅡ(APACHEⅡ)scores and the length of hospital stays.Patients were stratified by prognosis into death group and survial group,by drug resistance status into resistant and non-resistant groups.Univariate and multivariate Logistic regression identified risk factors for mortality and antimicrobial resistance.Draw the receiver operator characteristic curve(ROC curve)to evaluate the predictive value of each risk factor for patient prognosis and drug resistance occurrence.Results A total of 677 patients with suspected postoperative infection in the ICU were enrolled.There were 96 deaths and 591 survivors.① Analysis of risk factors affecting prognosis:univariate analysis showed that compared with the survival group,the patients in the had a higher APACHEⅡscore,the proportion of patients with previous cerebrovascular disease,surgery sites in the abdomen,chest,brain,pelvis,limbs,other areas,as well as those with pulmonary infection,bloodstream infection,urinary tract infection,Gram-positive bacterial infection(Candida),fungal infection,multi-drug resistant bacterial infection was higher,and the length of hospital stay was shorter(all P<0.05).Multivariate Logistic regression analysis identified higher APACHEⅡscore[odds ratio(OR)=1.15,95%confidence interval(95%CI)was 1.11-1.20],pulmonary infection(OR=4.07,95%CI was 2.05-8.11),bloodstream infection(OR=2.61,95%CI was 1.52-4.51),and urinary tract infection(OR=2.20,95%CI was 1.01-4.42)were independent risk factors for prognosis(all P<0.05).The ROC curve analysis showed that the death risk prediction model established based on the above independent risk factors had certain predictive value for the prognosis of ICU postoperative patients with suspected infection,area under the curve(AUC)=0.820,95%CI was 0.770-0.860,P<0.05.②Regarding antimicrobial resistance:250 patients developed resistance and 427 did not.Univariate analysis showed compared with the non-resistant group,the APACHEⅡscore,the proportion of patients with cerebrovascular diseases,hematological diseases,surgeries at chest,brain,limbs,other sites,as well as those with pulmonary infection,bloodstream infection,urinary tract infection,intracranial infection,Gram-negative bacillus infection,and Gram-positive cocci infection(Staphylococcus epidermidis,Staphylococcus aureus,Enterococcus faecalis),and the mortality rate in the resistant group were significantly higher,the proportion of patients with surgeries at abdominal cavity,pelvic cavity and abdominal cavity infection were significantly lower,and the length of hospital stay was significantly longer(all P<0.05).Multivariate Logistic regression analysis bloodstream infection(OR=4.00,95%CI was 2.22-7.19),urinary tract infection(OR=3.25,95%CI was 1.47-7.17),Klebsiella pneumoniae infection(OR=2.23,95%CI was 11.22-44.02),Acinetobacter baumannii infection(OR=48.12,95%CI was 20.10-115.17),Pseudomonas aeruginosa infection(OR=34.06,95%CI was 13.00-89.25),Escherichia coli infection(OR=24.97,95%CI was 10.55-59.13),Stenotrophomonas maltophilia infection(OR=19.04,95%CI was 3.30-109.96),and Staphylococcus aureus infection(OR=13.48,95%CI was 4.57-39.78)were independent risk factors for resistance(all P<0.01).The ROC curve analysis showed that the predictive model for drug resistance established based on the above independent risk factors had certain predictive value for drug resistance in adult patients with suspected infections after surgery in the ICU.The AUC=0.920,95%CI was 0.890-0.940,P<0.05.Conclusion Higher APACHEⅡscores and the presence of pulmonary,bloodstream,or urinary tract infections were associated with increased mortality in ICU patients with suspected postoperative infection.Patients with bloodstream or urinary tract infections,or infections caused by Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,Escherichia coli,Stenotrophomonas maltophilia,or Staphylococcus aureus,had significantly higher odds of developing antimicrobial resistance.

Objective:To analyze the application effects of ultrasound-guided superior laryngeal nerve block combined with cricothyroid membrane puncture on anesthesia for older adult patients with obesity.Methods:A case-control study was conducted on the clinical data of 85 older adult patients with difficult airways who underwent surgical treatment at Marine Police Corps Hospital of Chinese People's Armed Police Force from March 2021 to June 2023. Based on the different methods of anesthesia for tracheal intubation, the patients were divided into a control group ( n = 40) and an observation group ( n = 45). The control group received conventional superior laryngeal nerve block combined with cricothyroid membrane puncture, while the observation group received ultrasound-guided superior laryngeal nerve block combined with cricothyroid membrane puncture. The success rate of tracheal intubation, time taken for tracheal intubation, hemodynamic indicators, stress indicators, and the incidence of adverse reactions related to anesthesia were compared between the two groups. Results:In the observation group, the first-attempt tracheal intubation success rate was 87% (39/45), and the overall success rate for tracheal intubation was 98% (44/45), both of which were significantly higher than those in the control group [68% (27/40), 95% (38/40); χ2 = 4.48, 4.58, both P<0.05]. The time taken for tracheal intubation in the observation group was significantly shorter than that in the control group [(36.41 ± 5.23) minutes vs. (39.50 ± 4.42) minutes; t = 2.98, P<0.05]. During tracheal intubation and at the start of surgery, the observation group exhibited lower heart rates and higher mean arterial pressures compared with the control group ( t = 4.58, 4.65, -1.90, -2.14, all P<0.05). The cortisol and norepinephrine concentrations in the observation group were (23.12 ± 1.63) ng/L and (1 436.13 ± 225.60) pmol/L, respectively, both of which were significantly lower than those in the control group [(28.33 ± 2.29) ng/L, (1 784.50 ± 217.79) pmol/L; t = 12.59, 7.39, both P<0.05]. The incidence of anesthesia-related adverse reactions in the observation group was significantly lower than that in the control group [7% (3/45) vs. 25% (10/40); χ2 = 4.17, P<0.05]. Conclusions:Ultrasound-guided superior laryngeal nerve block combined with cricothyroid membrane puncture can enhance the success rate of tracheal intubation prior to general anesthesia in older adult patients with obesity. This approach helps maintain hemodynamic stability, reduces stress responses, and demonstrates a high level of safety.