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.

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.

Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans ; Parkinson Disease/microbiology* ; Gastrointestinal Microbiome/physiology* ; Dysbiosis/microbiology*

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Hippo signaling is a highly conserved pathway central to diverse cellular processes. Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers. Recent studies have uncovered that, in addition to the classical signaling cascade regulation, biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling. In this review, we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation, with a particular focus on transcriptional activation mediated by Yes-associated protein (YAP)/transcriptional coactivator with post-synaptic density-95, disks-large, and zonula occludens-1 (PDZ)-binding domain (TAZ) condensates. Furthermore, we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma (FUS) in modulating the biophysical properties of TAZ condensates, which in turn influence their transcriptional activity and pro-tumorigenic functions. These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.
Humans ; Signal Transduction ; Hippo Signaling Pathway ; Protein Serine-Threonine Kinases/physiology* ; Animals ; Biomolecular Condensates/metabolism* ; Transcription Factors/metabolism* ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/metabolism* ; Neoplasms ; Transcriptional Activation ; Intracellular Signaling Peptides and Proteins/metabolism*

Objective To analyze the influencing factors of clinical pregnancy and live birth rates in patients undergoing frozen-thawed embryo transfer(FET)for the first time.Methods The clinical data of 1 458 patients who underwent FET cycle-assisted pregnancy for the first time were retrospectively analyzed and divided into four groups according to clinical pregnancy and live bith outcomes.The clini-cal data were compared to analyze the factors affecting clinical pregnancy and live birth rates in FET cycles that were included in multiple logistic regression analysis.Results Of the 1458 cycles,the clinical pregnancy and live birth rates were 44.0% and 34.0%,respectively.The mean age of the clinical pregnancy and live birth groups was lower than that in non-clinical pregnancy and stillbirth groups(P<0.05).The clinical pregnancy and live birth rates of patients aged<35 years were higher than those aged≥35 years(P<0.05).The clinical preg-nancy and live birth rates of patients with≥8 mm endometrial thickness were higher than those with<8 mm endometrial thickness(P<0.05).The clinical pregnancy rate of natural cycles of endometrial preparation regimen was higher than that of HRT cycles(P<0.05).The clinical pregnancy and live birth rates of double-embryo transfers were higher than that of single-embryo transfers(P<0.05).The clinical pregnancy and live birth rates of blastocyst transfers were higher than those of cleavage stage(P<0.05).Conclusion Age,endometrial thickness,number of transplanted embryos,and embryo morphology were the independent factors influencing clinical pregnancy and live birth outcomes during FET cycle transplantation.

Objective:To explore the benefits of transradial diagnostic cerebral angiography in elderly patients and its correlation with morphometric parameters of the aortic arch.Methods:Clinical data and aortic arch CTA imaging parameters of patients who underwent cerebral angiography at the Department of Neurosurgery, Beijing Hospital, between May 2022 and April 2023 were retrospectively analyzed.The study aimed to compare the time taken for angiography via radial artery access in elderly patients versus younger patients, as well as via femoral artery access, and to evaluate the associated aortic arch morphology parameters.Results:A total of 101 patients' data were analyzed, with 67 males(66.3%)and an average age of 63.4±12.0 years.Among them, 69 patients(68.3%)were aged 60 and above.The arterial approach for 44 patients(43.6%)was radial, while 57 cases(56.4%)used the femoral artery approach.In the elderly group, 14 cases(20.6%), 31 cases(45.6%), and 23 cases(33.8%)had type Ⅲ aortic arch, respectively.For younger patients, 17 cases(53.1%), 12 cases(37.5%), and 3 cases(9.4%)fell into these categories.The distribution difference was statistically significant( χ2=12.765, P=0.002).Elderly patients had a larger aortic arch width angle compared to younger patients(106°±12°and 100°±12°, t=2.334, P=0.022).The time for whole-brain angiography via radial artery was shorter for elderly patients than via femoral artery(39.8±29.5 minutes and 52.2±28.4 minutes, respectively, t=1.845, P=0.070).In young patients, there was no significant time difference between the two approaches(42.3±30.4 minutes for radial artery and 34.6±11.2 minutes for femoral artery, t=1.026, P=0.313).In the type Ⅱ aortic arch group, the average times for transradial and transfemoral approaches were 38.1±21.7 minutes and 46.7±32.2 minutes, respectively( t=1.020, P=0.314).The average times for the type Ⅲ aortic arch group were 41.9±37.3 minutes and 48.9±20.7 minutes, respectively.Correlation analysis revealed a significant negative correlation between the duration of radial artery access and the distance from the origin of the innominate artery to the left subclavian artery(Pearson correlation coefficien( r=-0.372, P=0.014). Conclusions:In elderly patients, particularly those with type Ⅱ or Ⅲ aortic arch or a wide aortic arch, diagnostic cerebral angiography using transradial access is preferable to femoral access.The distance between the innominate artery and the left subclavian artery origin could impact the duration of the procedure.

Objective:To investigate the role of hepatitis B virus X protein (HBx) in glomerular podocyte immune disorder and its regulatory mechanism.Methods:Fourteen 6-week-old male hepatitis B virus (HBV) transgenic (HBV-Tg) mice were selected, and age-matched wild type (WT) mice were as controls. They were fed to different weeks, and 24 h urinary protein, blood biochemistry, renal pathology and podocyte changes under electron microscope were detected. The expression of HBx and the infiltration of immune cells in kidney tissue of HBV-Tg mice were observed by immunohistochemistry. Human podocyte cell line was transfected with pcDNA3.1/myc-HBx plasmid, and the localization of HBx and Nephrin in podocytes was detected by immunofluorescence. The expression of major histocompatibility complex Ⅱ (MHC-Ⅱ) and co- stimulatory molecule CD40 on the cell surface was detected by flow cytometry. The contents of multiple cytokines in cell culture supernatants were determined by enzyme-linked immunosorbent assay. Transcriptome sequencing (RNA-seq) was used to screen the downstream related genes regulated by HBx, and real-time quantitative PCR was used to verify their expressions. After overexpression or silencing of Notch1 gene with overexpressed plasmids or short hairpin RNA (shRNA) in podocytes, the effects on the expression of immune molecules and cytokines secretion was observed. The Notch receptor inhibitor N-[N-(3, 5-difluorophenyl-l- alanyl)]-(s)-phenylglycine tert-butyl ester (DAPT) was used to block Notch1 signaling pathway in HBV-Tg mice, and then blood biochemistry, renal pathological changes and infiltration of immune cells in kidney tissue were observed. Results:Twenty-four-hour urine protein, serum creatinine and urea nitrogen levels were markedly increased (all P<0.05) and renal pathological injury was significantly aggravated in HBV-Tg mice than those in WT mice. Also, HBx was up-regulated and immune cells infiltrated in the glomerulus of HBV-Tg mice. After transfection with HBx in podocytes, the expression of MHC-Ⅱ and CD40 on the cellular surface was up-regulated (all P<0.05), the contents of monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor -α (TNF-α) and interleukin (IL)-1β in the supernatants were increased (all P<0.05), and the secretion of IL-4 and interferon γ (IFN-γ) was unbalanced. RNA-seq screened downstream genes of HBx, such as Notch1, PLA2R, TLR4, etc; and further confirmed that HBx could promote the up-regulation of Notch1 mRNA and protein (all P<0.05). After over-expression of Notch1 gene, HBx-induced expression of MHC-Ⅱ and CD40 on the cellular surface was significantly up-regulated (all P<0.05), and the contents of MCP-1, TNF-α and IL-1β in the supernatants were obviously increased (all P<0.05), and the imbalance of IL-4/IFN-γ was further aggravated. After Notch1 gene silencing, the above results showed the opposite changes. In vivo, the results indicated that serum creatinine levels were obviously decreased (all P<0.05), renal pathological injury and immune cell infiltration were significantly alleviated in HBV-Tg+DAPT group than those in HBV-Tg+DMSO group. Conclusions:HBx protein can promote the up-regulation of Notch1 signaling pathway in podocytes. And Notch1 signaling pathway promotes the expression of immune molecules on the surface of podocytes and regulates the imbalance of cytokines, then causes glomerular injury and dysfunction of immune microenvironment.