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.

The Golgi body, a core organelle in eukaryotic cells, plays a critical role in protein modification, sorting, vesicular transport, and serves as a key site for lipid synthesis and glycosylation. Glucose and lipid metabolism are central processes for cellular energy maintenance and biosynthesis, and are closely linked to Golgi function. Recent studies have revealed the extensive involvement of the Golgi body in regulating glucose and lipid metabolism, where maintaining its structural and functional homeostasis is crucial for normal physiological activity. Under various stress conditions such as acidosis, hypoxia, and nutrient deficiency, the Golgi body undergoes structural and functional disruption, leading to Golgi stress. This in turn activates specific signaling pathways, such as those mediated by the cAMP-responsive element binding protein 3 (CREB3) and proteoglycans, to alleviate Golgi stress and enhance Golgi function. Golgi stress contributes to glucose and lipid metabolic disorders by affecting the activity of insulin receptors, glucose transporters, and lipid metabolism-related enzymes. For example, Golgi stress triggers the cleavage and release of the active fragment of CREB3, which enters the nucleus and upregulates the transcription of ADP-ribosylation factor 4 (ARF4) and key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). ARF4 promotes vesicle retrograde transport between the Golgi and endoplasmic reticulum, maintains secretory capacity, and enhances hepatic glucose output. This pathway is particularly active under high-fat or lipotoxic stress, leading to fasting hyperglycemia. When damaged Golgi components accumulate beyond a tolerable threshold, the cell initiates an autophagic response, selectively encapsulating the damaged Golgi into autophagosomes, which then fuse with lysosomes to form autolysosomes, leading to Golgiphagy. This process results in the degradation and clearance of damaged Golgi, thereby regulating Golgi quantity, quality, and function. Golgiphagy also plays a significant role in regulating glucose and lipid metabolism. For instance, under high-glucose conditions, autophagic flux may be suppressed, impairing the timely clearance and renewal of damaged Golgi, compromising its normal function, and further exacerbating glucose metabolism disorders. Additionally, Golgiphagy may participate in lipid degradation and influence lipid synthesis and transport. Research indicates that Golgi stress and Golgiphagy play important roles in glucose and lipid metabolism-related diseases. For example, the leucine zipper protein (LZIP) under Golgi stress conditions can promote hepatic steatosis. In mouse primary cells and human tissues, LZIP induces the expression of apolipoprotein A-IV (APOA4), which increases peripheral free fatty acid uptake, resulting in lipid accumulation in the liver and contributing to the development of fatty liver disease. This review systematically outlines the structure and function of the Golgi apparatus, the molecular regulatory mechanisms of Golgi stress and Golgiphagy, and their synergistic roles. It further elaborates on how Golgi stress and Golgiphagy participate in the regulation of glucose and lipid metabolism, discusses their clinical significance in related diseases such as diabetes, fatty liver disease, and obesity, and highlights potential novel therapeutic strategies from the perspective of Golgi-targeted medicine. Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.

The Golgi body, a core organelle in eukaryotic cells, plays a critical role in protein modification, sorting, vesicular transport, and serves as a key site for lipid synthesis and glycosylation. Glucose and lipid metabolism are central processes for cellular energy maintenance and biosynthesis, and are closely linked to Golgi function. Recent studies have revealed the extensive involvement of the Golgi body in regulating glucose and lipid metabolism, where maintaining its structural and functional homeostasis is crucial for normal physiological activity. Under various stress conditions such as acidosis, hypoxia, and nutrient deficiency, the Golgi body undergoes structural and functional disruption, leading to Golgi stress. This in turn activates specific signaling pathways, such as those mediated by the cAMP-responsive element binding protein 3 (CREB3) and proteoglycans, to alleviate Golgi stress and enhance Golgi function. Golgi stress contributes to glucose and lipid metabolic disorders by affecting the activity of insulin receptors, glucose transporters, and lipid metabolism-related enzymes. For example, Golgi stress triggers the cleavage and release of the active fragment of CREB3, which enters the nucleus and upregulates the transcription of ADP-ribosylation factor 4 (ARF4) and key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). ARF4 promotes vesicle retrograde transport between the Golgi and endoplasmic reticulum, maintains secretory capacity, and enhances hepatic glucose output. This pathway is particularly active under high-fat or lipotoxic stress, leading to fasting hyperglycemia. When damaged Golgi components accumulate beyond a tolerable threshold, the cell initiates an autophagic response, selectively encapsulating the damaged Golgi into autophagosomes, which then fuse with lysosomes to form autolysosomes, leading to Golgiphagy. This process results in the degradation and clearance of damaged Golgi, thereby regulating Golgi quantity, quality, and function. Golgiphagy also plays a significant role in regulating glucose and lipid metabolism. For instance, under high-glucose conditions, autophagic flux may be suppressed, impairing the timely clearance and renewal of damaged Golgi, compromising its normal function, and further exacerbating glucose metabolism disorders. Additionally, Golgiphagy may participate in lipid degradation and influence lipid synthesis and transport. Research indicates that Golgi stress and Golgiphagy play important roles in glucose and lipid metabolism-related diseases. For example, the leucine zipper protein (LZIP) under Golgi stress conditions can promote hepatic steatosis. In mouse primary cells and human tissues, LZIP induces the expression of apolipoprotein A-IV (APOA4), which increases peripheral free fatty acid uptake, resulting in lipid accumulation in the liver and contributing to the development of fatty liver disease. This review systematically outlines the structure and function of the Golgi apparatus, the molecular regulatory mechanisms of Golgi stress and Golgiphagy, and their synergistic roles. It further elaborates on how Golgi stress and Golgiphagy participate in the regulation of glucose and lipid metabolism, discusses their clinical significance in related diseases such as diabetes, fatty liver disease, and obesity, and highlights potential novel therapeutic strategies from the perspective of Golgi-targeted medicine. Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.

[摘 要] 目的：探讨月见草素B调控磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/核因子-κB（NF-κB）通路对卵巢癌SKOV3细胞恶性生物学行为的影响。方法：CCK-8法测定月见草素B对SKOV3细胞的半数抑制浓度（IC50），参考IC₅₀值及相关文献确定后续实验剂量。SKOV3细胞分为对照组，月见草素B低（6.25 μmol/L）、中（12.5 μmol/L）、高（25 μmol/L）剂量组，PI3K抑制剂（LY294002）组，月见草素B高剂量 + PI3K激活剂（740Y-P）组。CCK-8法、5-乙炔基-2'-脱氧尿苷（EdU）染色法检测各组细胞增殖能力；Transwell侵袭实验、划痕实验、流式细胞术分别检测各组细胞侵袭、迁移能力与凋亡情况；RT-qPCR检测各组细胞中增殖相关基因细胞周期蛋白D1（Cyclin D1）、迁移相关基因迁移侵袭增强子1（MIEN1）及凋亡相关基因p53 mRNA表达情况；Western blotting检测各组细胞中PI3K/AKT/NF-κB通路相关蛋白p-PI3K、p-AKT、NF-κB p65的表达。结果：月见草素B处理SKOV3细胞24 h的IC₅₀值为28.70 μmol/L。与对照组相比，月见草素B低、中、高剂量组及LY294002组SKOV3细胞增殖能力、侵袭细胞数及划痕愈合率均降低（均P < 0.05），Cyclin D1、MIEN1 mRNA及p-PI3K、p-AKT、NF-κB p65蛋白表达下调（均P < 0.05），而细胞凋亡率与p53 mRNA表达则升高（均P < 0.05）；与LY294002组相比，高剂量月见草素B对SKOV3细胞增殖能力、侵袭细胞数及划痕愈合率的抑制作用更显著（均P < 0.05），对Cyclin D1、MIEN1 mRNA及p-PI3K、p-AKT、NF-κB p65蛋白的下调及对细胞凋亡率与p53 mRNA表达的上调均更明显（均P < 0.05）。与月见草素B高剂量组相比，月见草素B高剂量+740Y-P组SKOV3细胞增殖能力、侵袭细胞数及划痕愈合率升高（均P < 0.05），Cyclin D1、MIEN1 mRNA及p-PI3K、p-AKT、NF-κB p65蛋白表达上调（均P < 0.05），细胞凋亡率与p53 mRNA表达降低（P < 0.05）。结论：月见草素B可能通过抑制PI3K/AKT/NF-κB通路，抑制卵巢癌SKOV3细胞增殖、侵袭与迁移，并诱导细胞凋亡。

ObjectiveTo investigate the effect of honokiol on proliferation， apoptosis， migration， and invasion of gastric cancer cells and its underlying mechanistic. MethodsHuman gastric cancer cell lines HGC-27 and AGS were treated with Honokiol at concentrations of 0， 15， and 25 μmol/L. CCK-8 assays were conducted to determine the half maximal inhibitory concentration （IC₅₀） for both cell lines. Cell viability， proliferation， migration， and invasion capabilities were assessed using CCK-8， colony formation， wound healing， Transwell migration and Transwell invasion assays. Apoptosis rates were measured via flow cytometry. Western blot analysis examined proteins related to proliferation， apoptosis， migration， invasion， and the endoplasmic reticulum stress pathway ATF4-CHOP-TRIB3. ResultsCompared with the control group， treatment with 15 and 25 μmol/L Honokiol significantly reduced the proliferation， colony formation， migration， and invasion capabilities of the two gastric cancer cell lines， while significantly increasing the apoptosis rate （P<0.05）. Additionally， compared to the control group， the protein expression levels of neural cadherin（N-cadherin）， Vimentin， proliferating cell nuclear antigen（PCNA）， and B-cell lymphoma/leukemia-2 protein（Bcl-2）decreased in the two gastric cancer cell lines after treatment with 15 and 25 μmol/L Honokiol， while the protein expression levels of epithelial cadherin（E-cadherin）， Bcl-2-associated X protein（Bax）， activating transcription factor 4（ATF4）， endoplasmic reticulum stress-related protein（CHOP）， and tribbles homolog 3（TRIB3）increased（P<0.05）. ConclusionHonokiol promotes apoptosis and inhibits proliferation， migration， and invasion of gastric cancer HGC-27 and AGS cells by regulating the ERS signaling pathway ATF4/CHOP/TRIB3.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients' quality of life. Zhengqing Fengtongning (ZF) is a traditional Chinese medicine preparation used to treat RA. ZF may cause liver injury. In this study, we aimed to develop a prediction model for abnormal liver function caused by ZF. METHODS: This retrospective study collected data from multiple centers from January 2018 to April 2023. Abnormal liver function was set as the target variable according to the alanine transaminase (ALT) level. Features were screened through univariate analysis and sequential forward selection for modeling. Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data. RESULTS: This study included 1,913 eligible patients. The LightGBM model exhibited the best performance (accuracy = 0.96) out of the 10 learning models. The predictive metrics of the LightGBM model were as follows: precision = 0.99, recall rate = 0.97, F1_score = 0.98, area under the curve (AUC) = 0.98, sensitivity = 0.97 and specificity = 0.85 for predicting ALT < 40 U/L; precision = 0.60, recall rate = 0.83, F1_score = 0.70, AUC = 0.98, sensitivity = 0.83 and specificity = 0.97 for predicting 40 ≤ ALT < 80 U/L; and precision = 0.83, recall rate = 0.63, F1_score = 0.71, AUC = 0.97, sensitivity = 0.63 and specificity = 1.00 for predicting ALT ≥ 80 U/L. ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels, the combination of TNF-α inhibitors, JAK inhibitors, methotrexate + nonsteroidal anti-inflammatory drugs, leflunomide, smoking, older age, and females in middle-age (45-65 years old). CONCLUSION This study developed a model for predicting ZF-induced abnormal liver function, which may help improve the safety of integrated administration of ZF and Western medicine. Please cite this article as: Yu Z, Kou F, Gao Y, Lyu CM, Gao F, Wei H. A machine learning model for predicting abnormal liver function induced by a Chinese herbal medicine preparation (Zhengqing Fengtongning) in patients with rheumatoid arthritis based on real-world study. J Integr Med. 2025; 23(1): 25-35.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Middle Aged ; Male ; Retrospective Studies ; Machine Learning ; Adult ; Aged ; Liver/physiopathology* ; Alanine Transaminase/blood*

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*