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.

BACKGROUND:Studies have shown that lipid metabolism and related diseases can affect the development of osteoporosis.OBJECTIVE:Using bibliometric visualization analysis software to analyze and summarize the frontier content and research hotspots in the field of lipid metabolism affecting osteoporosis.METHODS:Using the Web of Science core collection database as the retrieval platform,relevant literature regarding the effect of lipid metabolism on osteoporosis from 2004 to 2024 was retrieved.VOSviewer and CiteSpace were used for bibliometric and visual analyses.RESULTS AND CONCLUSION:A total of 1 277 articles were included,and the number of articles on the effect of lipid metabolism on osteoporosis at home and abroad was increasing year by year.The number of articles published in China was 417,ranking first,and the United States was 243,ranking second.Shanghai Jiao Tong University ranked first with 30 articles.Professor Rosen Clifford J from Tufts University School of Medicine and Professor Recker Robert R from Clayton University were the most cited authors.The number of documents published in BONE in the Netherlands ranked first,and the JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM in England was the most cited journal.Bone mineral density,bone metabolism,menopause,and obesity were the core keywords,and they were also research hotspots in this field.The above results show that in the past 20 years,research in the field of lipid metabolism affecting osteoporosis has focused on the role of abnormal lipid metabolism in bone mineral density and bone metabolism,thereby regulating osteoporosis and post-menopause osteoporosis.Clarifying the pathway of this mechanism and"bone-lipid balance"is the future research idea and direction.

BACKGROUND:Studies have shown that lipid metabolism and related diseases can affect the development of osteoporosis.OBJECTIVE:Using bibliometric visualization analysis software to analyze and summarize the frontier content and research hotspots in the field of lipid metabolism affecting osteoporosis.METHODS:Using the Web of Science core collection database as the retrieval platform,relevant literature regarding the effect of lipid metabolism on osteoporosis from 2004 to 2024 was retrieved.VOSviewer and CiteSpace were used for bibliometric and visual analyses.RESULTS AND CONCLUSION:A total of 1 277 articles were included,and the number of articles on the effect of lipid metabolism on osteoporosis at home and abroad was increasing year by year.The number of articles published in China was 417,ranking first,and the United States was 243,ranking second.Shanghai Jiao Tong University ranked first with 30 articles.Professor Rosen Clifford J from Tufts University School of Medicine and Professor Recker Robert R from Clayton University were the most cited authors.The number of documents published in BONE in the Netherlands ranked first,and the JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM in England was the most cited journal.Bone mineral density,bone metabolism,menopause,and obesity were the core keywords,and they were also research hotspots in this field.The above results show that in the past 20 years,research in the field of lipid metabolism affecting osteoporosis has focused on the role of abnormal lipid metabolism in bone mineral density and bone metabolism,thereby regulating osteoporosis and post-menopause osteoporosis.Clarifying the pathway of this mechanism and"bone-lipid balance"is the future research idea and direction.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

AIM:To investigate the therapeutic effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-Exos)on diabetic retinopathy(DR)in rats, with a focus on their ability to modulate oxidative stress and inflammatory responses through the TLR4/NF-κB signaling pathway.METHODS:Streptozotocin(STZ)-induced diabetic Sprague-Dawley(SD)rats were randomly divided into four groups: Group 1 [normal+phosphate-buffered saline(PBS)], Group 2(normal+Exos), Group 3(DR+PBS), and Group 4(DR+Exos). At the 8th week after modeling, BMSC-Exos or PBS were injected intravitreally. Retinal tissues were collected at the 16th week for histological analysis [hematoxylin and eosin(HE)staining], apoptosis detection(TUNEL). Oxidative stress markers [8-OHdG, superoxide dismutase(SOD), and glutathione(GSH)] were assessed, and inflammatory cytokines [enzyme-linked immunosorbent assay(ELISA)for interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α)], and molecular profiling [quantitative polymerase chain reaction(qPCR)for TLR4, NF-κB, and VEGF] were measured.RESULTS:The BMSC-Exos treatment significantly suppressed the activation of the TLR4/NF-κB pathway in DR rats(P<0.01), which was accompanied by reduced retinal vascular leakage(Evans blue assay, P<0.001), decreased apoptosis(TUNEL, P<0.05), and attenuated oxidative stress(elevated SOD and GSH, reduced 8-OHdG, P<0.05). The levels of inflammatory cytokines(IL-6 and TNF-α)were markedly decreased(P<0.01).CONCLUSION:BMSC-Exos alleviate DR by suppressing the TLR4/NF-κB axis, thus reducing oxidative damage, inflammation, and microvascular dysfunction. This research offers a novel therapeutic approach for early-stage DR.

By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation， this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine （TCM） phenomics， we proposed utilizing multi-modal data from literature research， cross-sectional studies， and cohort follow-ups， combined with artificial intelligence technology， to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally， by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system， we developed three major modules including information extraction， multi-modal phenotypic modeling， and information output， to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis， treatment evaluation， and research， while also offering insights and methods for intelligent TCM diagnosis.

The increasing prevalence of aging has led to a rising incidence of comorbidity of sarcopenia and obesity, posing significant burdens on socioeconomic and public health. Current research has systematically explored the pathogenesis of each condition; however, the mechanisms underlying their comorbidity remain unclear. This study reviews the current literature on sarcopenia and obesity in the aging population, focusing on their shared biological mechanisms, which include loss of autophagy, abnormal macrophage function, mitochondrial dysfunction, and reduced sex hormone secretion. It also identifies metabolic mechanisms such as insulin resistance, vitamin D metabolism abnormalities, dysregulation of iron metabolism, decreased levels of nicotinamide adenine dinucleotide, and gut microbiota imbalances. Additionally, this study also explores the important role of genetic factors, such as alleles and microRNAs, in the co-occurrence of sarcopenia and obesity. A better understanding of these mechanisms is vital for developing clinical interventions and preventive strategies.
Humans ; Sarcopenia/physiopathology* ; Obesity/physiopathology* ; Aging/physiology* ; Autophagy/physiology* ; Insulin Resistance ; Comorbidity ; Vitamin D/metabolism* ; Gonadal Steroid Hormones/metabolism* ; Gastrointestinal Microbiome ; Mitochondria ; MicroRNAs

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

Objective To investigate the independent risk factors affecting the prognosis of chronic active antibody-mediated rejection (caAMR) after kidney transplantation. Methods A retrospective analysis was conducted on 61 patients who underwent renal biopsy and were diagnosed with caAMR. The patients were divided into caAMR group (n=41) and caAMR+TCMR group (n=20) based on the presence or absence of concurrent acute T cell-mediated rejection (TCMR). The patients were followed up for 3 years. The value of 24-hour urinary protein and estimated glomerular filtration rate (eGFR) at the time of biopsy in predicting graft loss was assessed using receiver operating characteristic (ROC) curves. The independent risk factors affecting caAMR prognosis were analyzed using the LASSO-Cox regression model. The correlation between grouping, outcomes, and Banff scores was compared using Spearman rank correlation matrix analysis. Kaplan-Meier analysis was used to evaluate the renal allograft survival rates of each subgroup. Results The 3-year renal allograft survival rates for the caAMR group and the caAMR+TCMR group were 83% and 79%, respectively. The area under the ROC curve (AUC) for predicting 3-year renal allograft loss was 0.83 ［95% confidence interval (CI) 0.70-0.97］ for eGFR and 0.78 (95% CI 0.61-0.96) for 24-hour urinary protein at the time of biopsy. LASSO-Cox regression analysis and Kaplan-Meier analysis showed that eGFR≤25.23 mL/(min·1.73 m²) and the presence of donor-specific antibody (DSA) against human leukocyte antigen (HLA) class I might be independent risk factors affecting renal allograft prognosis, with hazard ratios of 7.67 (95% CI 2.18-27.02) and 5.13 (95% CI 1.33-19.80), respectively. A strong correlation was found between the Banff chronic lesion indicators of renal interstitial fibrosis and tubular atrophy (P<0.05). Conclusions The presence of HLA class I DSA and eGFR≤25.23 mL/(min·1.73 m²) at the time of biopsy may be independent risk factors affecting the prognosis of caAMR.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.