Objective: To explore the impact of adverse childhood experiences (ACEs) on health risk behaviors (HRBs) among college students and the mediating role of psychological symptoms, so as to provide a basis for developing intervention strategies. Methods: From March to April 2023, a convenience cluster sample of 1 801 students from 12 universities in Nanning, Liuzhou, Guilin, Wuzhou of Guangxi completed an online survey. A self designed questionnaire, Adverse Childhood Experiences-International Questionnaire (ACE-IQ) and Symptom Checklist-90 (SCL-90) were used for evaluation tools. Binary Logistic regression, structural equation modeling (SEM) and Bootstrap methods were used to analyze the associations and mediating effects. Results: Overall, 71.2% of college students experienced at least one type of ACE, with emotional neglect (40.3%) and emotional abuse ( 25.2 %) having the highest detection rates. The top three HRBs were unhealthy diet (77.8%), physical inactivity (54.1%), and smoking/alcohol use (18.5%). Logistic regression showed that poor family functioning, abuse, and extra familial violence were each associated with an increased risk of smoking/alcohol use ( OR =1.14, 1.11, 1.18) and deliberate self harm ( OR =1.26, 1.19,1.30) (all P <0.05). Experience of abuse increased the risk of high risk sexual behavior and family dysfunction increaded the risk of physical inactivity, respectively ( OR = 1.07 , 1.04, both P <0.05). Mediation analysis revealed that anxiety ( β =0.20) and depression ( β = 0.09 ) partially mediated the pathway from poor family functioning to deliberate self harm; paranoia ( β =0.02) partially mediated the pathway from abuse to high risk sexual behavior; and obsessive-compulsive symptoms ( β =0.26) and depression ( β =0.10) partially mediated the pathway from extra familial violence to deliberate self harm (all P <0.05). Conclusion Psychological symptoms play a mediating role in the association between ACEs and HRBs, and mental health interventions may reduce the risk of HRBs among college students.

Functional constipation （FC） is a clinically common functional bowel disorder characterized by a protracted course and associations with various chronic disorders and psychological abnormalities. Although not life-threatening， FC significantly impairs patients' quality of life. FC subtypes include slow-transit constipation （STC）， defecatory disorder （DD）， and normal-transit constipation （NTC）. The pathological mechanisms underlying FC have not been fully elucidated， and overall clinical efficacy remains unsatisfactory. Animal models of FC serve as essential tools for the study of disease mechanisms and the development of novel therapeutics. This article systematically reviews the current state of research on the animal models of FC and identifies that rodents， particularly rats and mice， are the most commonly used species. Dogs and pigs are also employed in complex intervention studies due to their physiological similarities to humans， though their use is limited by housing challenges and ethical considerations. Induction methods vary across different FC subtypes. STC models are primarily established with chemical agents such as loperamide or compound diphenoxylate. DD modeling often involves low-fiber diets combined with methylene blue injection or rectal narrowing. NTC modeling mainly relies on low-fiber dietary interventions. In addition， disease-syndrome combination models based on traditional Chinese medicine （TCM） theory have been developed， encompassing excess patterns such as heat accumulation， cold accumulation， and Qi stagnation， as well as deficiency patterns including Qi deficiency， blood deficiency， Yin deficiency， and Yang deficiency. These are achieved through an approach of disease model + syndrome induction， enabling the integration of mechanisms from both Western and TCM perspectives. Models are evaluated from two aspects： disease and syndrome manifestations （e.g.， colonic transit， secretory function， and TCM syndrome indicators such as mental state and body weight） and disease mechanisms （e.g.， enteric nervous system， interstitial cells of Cajal， smooth muscle cells， gut microbiota， and metabolites）. However， current research still faces challenges such as poor consistency in some models， non-specific interference in mechanism interpretation， insufficient studies on NTC， and lack of TCM tongue and pulse diagnosis in evaluation. Future efforts should focus on optimizing model stability and specificity to provide a more reliable experimental basis for investigating the pathological mechanisms of FC and developing therapeutic agents.

ObjectiveTo explore the effects of serine hydroxymethyltransferase 1 （SHMT1） rs1979277 polymorphisms on pharmacokinetic characteristics and clinical prognosis of methotrexate （MTX） in children with acute lymphoblastic leukemia （ALL）. MethodsMatrix-assisted laser desorption/ionization time of flight mass spectrometry was used for SHMT1 rs1979277 genotyping in children with ALL . Clinical data including serum MTX concentrations， incidences of adverse events， and ALL relapse after chemotherapy with MTX were collected. The associations of SHMT1 rs1979277 G>A genotypes with dose-adjusted serum concentrations （C/D ratios）， adverse events of MTX， and relapse were analyzed. The associations between rs1979277 genotypes and SHMT1 expression were explored based on Bioinformatics methods. ResultsAmong the 146 children with ALL included， the rs1979277 GG homozygous genotype accounted for 85.62% （125/146）， while the GA heterozygous genotype accounted for 14.38% （21/146）. The frequency of the G allele was 92.81% （271/292）， while the A allele was only 7.19% （21/292）. Children with the GG homozygous genotype had higher median C/D ratios of MTX in 24 h ［12.06 （μmol·m²）/（L·g）］ and higher relapse rates （12.80%） than those in GA heterozygous genotype carriers ［10.96 （μmol·m²）/（L·g）， and 9.52%， respectively］. However， none of the above differences were statistically significant （all P>0.05）. The incidences of respiratory （19.05%） and liver disorders （33.33%） in children with the GA heterozygous genotype were significantly higher than those in GG homozygous genotype carriers （4.00% and 12.00%， respectively， P<0.05）. There were no statistically significant differences in the incidences of other adverse events. Bioinformatics analysis showed that the rs1979277 A allele was significantly associated with higher SHMT1 expression in multiple tissues， such as the tibial artery， pancreas， and adrenal gland （P<0.05）. ConclusionSHMT1 rs1979277 GA genotype may be a risk factor for respiratory and liver disorders in ALL children treated with MTX.

ObjectiveTo investigate the effect of neuromuscular electrical stimulation (NMES) on quadriceps muscle strength and walking for patients after anterior cruciate ligament reconstruction (ACLR). MethodsThirty-four patients after ACLR were selected at Beijing Rehabilitation Hospital of Capital Medical University from July, 2022 to October, 2023, and randomly divided into control group (n = 17) and experimental group (n = 17). Both groups received routine rehabilitation and functional training, and the experimental group received NMES during the functional training, while the control group received sham NMES, for eight weeks. Quadriceps peak torque-to-weight ratio, single-leg support phase and plantar impulses during walking were measured before and after intervention. ResultsTwo cases in the control group and three in the experimental group dropped down. Quadriceps peak torque-to-weight ratio improved in both groups after intervention (|t| > 17.578, P < 0.001), and improved more in the experimental group than in the control group (t = 4.714, P < 0.001); while the affected single-leg support phase and the affected/unaffected single-leg support phase ratio improved in both groups (|t| > 16.882, P < 0.001), and improved more in the experimental group than in the control group (t > 3.234, P < 0.01); and plantar impulses of all zones optimized in both groups (t > 9.221, P < 0.001), and were better in the experimental group than in the control group(|t| > 2.852, P < 0.01). ConclusionNMES may further improve quadriceps muscle strength, plantar pressure distribution during walking and single-leg support in patients after ACLR.

BACKGROUND: Circadian syndrome (CircS) may be closely linked to lifestyle, psychological, and occupational factors, but evidence is lacking. This study aimed to explore complex associations between lifestyle, psychological and occupational factors and CircS among employed people in southwestern China. METHODS: In this study, network analysis was used to identify complex associations between lifestyle, psychological and occupational factors and CircS in employed people from the Chinese Cohort of Working Adults (CCWA). The centrality of each variable was estimated by strength centrality index, which was calculated by the sum of edge weights connected to the variable. Bridge in the network was identified as the variables in the top 80 th percentile of overall bridge strength, which was defined as the most strongly connected variables across lifestyle, psychological and occupational factors and CircS. The differences were assessed in network structures between subgroups divided by the median score of the variable with the strongest bridge strengthen. RESULTS: Among 31,105 participants from CCWA, 5213 (16.76%) had CircS. In the constructed network, anxiety (edge weights: 0.28), smoking (edge weights: 0.15), drinking (edge weights: 0.10), perceived noise at work (edge weights: 0.08), and implicit health attitude (edge weights: -0.02) were directly related to CircS, with 83.31% of the variance for CircS explained by these neighboring factors. Anxiety was the most central variable (strength centrality: 1.20) in the network and the strongest bridge (bridge strength: 0.84) connecting all domains of variables. A stronger association between anxiety and CircS was observed in the network of participants with more severe anxiety (edge weight: 0.23) than those with less severe anxiety (edge weight: 0.03). CONCLUSION Anxiety had the strongest association with CircS and was the central factor with the highest strength centrality, also the bridge with the highest bridge strength in the network.
Humans ; Male ; Female ; Adult ; China ; Middle Aged ; Life Style ; Chronobiology Disorders/epidemiology*

Objective To establish a human intestinal organ-on-a-chip model using a multi-array chip array to simulate the microphysiological structure of the human intestine and to investigate the impact of ionizing radiation on radiation-induced damage to human intestinal cells.Methods Caco-2 and human umbilical vein endothelial cells(HUVECs)were co-cultured in an organ chip.The cells were subjected to fluid shear stress via a precision shaker.After 7 days of dynamic culture,the morphological structure of intestinal epithelial cells and venous endothelial cells within the intestinal organ chip was examined using phase contrast microscopy,immunofluorescence staining,and confocal microscopy for three-dimensional(3D)imaging.γ-H2AX and TUNEL immunofluorescence staining were employed to assess DNA damage and apoptosis in intestinal epithelial cells two days post-irradiation.Villin immunofluorescence staining was used to evaluate villus height three days post-irradiation.EdU incorporation assay and Ki67 immunofluorescence staining were conducted to observe the effects of ionizing radiation on the proliferation of intestinal epithelial cells.Results After 7 days of dynamic culture,phase contrast microscopy and immunofluorescence staining combined with confocal 3D imaging revealed that the upper intestinal epithelial cells in the middle compartment of the chip formed a 3D intestinal villus structure,while the vascular endothelial cells in the lower compartment developed a vascular network structure.The chip was subsequently irradiated by 10 Gy X-ray.Immunofluorescence staining results indicated that the mean fluorescence intensity of γ-H2AX and TUNEL in the irradiated group was significantly higher than in the non-irradiated group 2 days after irradiation(P＜0.01),and that the proportion of EDU+and Ki67+cells in the irradiated group was significantly lower than in the non-irradiated group three days after irradiation(P＜0.05).Conclusion Caco-2 cells and HUVECs co-culture on an organ chip can generate the biomimetic structure of human intestinal villus.Ionizing radiation has been found to shorten intestinal villus,increase DNA damage and apoptosis in intestinal epithelial cells,and inhibit the proliferation of these cells.

Objective : To investigate the expression and biological function of circular RNA(circRNA) hsa＿circ＿0002938 in gastric cancer. Methods : 45 pairs of tumor tissues and para-cancerous tissues from gastric cancer patients who underwent tumor reduction surgery at the hospital were collected. Human gastric cancer cells SGC-7901, BGC-823, HGC-27, MGC-803 and immortalized gastric mucosal epithelial cells GES-1 were routinely cultured. RT-qPCR was utilized to detect the expression of hsa＿circ＿0002938 in gastric cancer tissues and cells. Chi-square test was used to analyze its association with the clinicopathological characteristics of patients, and the Kaplan-Meier method was employed to assess the relationship between hsa＿circ＿0002938 expression levels and patient prognosis. The effects of hsa＿circ＿0002938 on the proliferation, migration and invasion abilities of gastric cancer cells were detected by CCK-8, scratch wound healing and Transwell assays. Bioinformatics was used to predict the miRNA and its downstream target genes that hsa＿circ＿0002938 might bind to. The competitive endogenous RNA regulatory network was constructed and the functions of the target genes were enriched. Results : The expression of hsa＿circ＿0002938 in gastric cancer tissues and cells was much higher than that in para-cancerous tissues and GES-1 cells(P<0.05). By contrast, patients in the high hsa＿circ＿0002938 expression group had significantly shorter 2-year progression-free survival than that in the low expression group after surgery(P<0.01). Moreover, knocking down the expression of hsa＿circ＿0002938 reduced the proliferative, migratory, and invasive abilities of gastric cancer cells(P<0.05). Bioinformatics predictive analysis showed that hsa＿circ＿0002938 could bind to hsa-miR-342-3p and hsa-miR-503-5p. The downstream target genes of miRNA were involved in several cancer-related pathways, like mitogen-activated protein kinase(MAPK), hippo and Wnt signaling pathway. Conclusion Hsa＿circ＿0002938, which is highly expressed in gastric cancer tissues and cells, is closely associated with poor patient prognosis. Knockdown of hsa＿circ＿0002938 inhibits the proliferation, migration, and invasion abilities of gastric cancer cells. The study reveals the potential role of hsa＿circ＿0002938 in the progression of gastric cancer, offering new insights into its prevention and treatment.

Objective:To explore the factors influencing the success rate of culturing patient-derived gastric and colorectal cancer organoids.Methods:From Feb 2022 to Oct 2023, 398 tumor tissue specimens from patients who underwent gastric cancer and colorectal cancer resection at the Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, were used for organoid culture. The clinicopathological factors affecting the success rate of organoid culture were analyzed.Results:The overall success rate of organoid culture in this group was 75.1% (299/398), with the success rate of gastric cancer organoid culture being 79.8%(154/193) and that of colorectal cancer being 70.7% (145/205). Different clinicopathological T stage ( χ2=4.765, P<0.05),histological type ( χ2=11.248, P<0.05), and tumor regression grade (TRG) grade after neoadjuvant chemotherapy ( χ2=7.797, P<0.05) were related to the success rate of organoid culture . Multivariate analysis showed that the TRG grade was an independent influencing factor( P=0.040). For colorectal cancer, different pathological T stage ( χ2=5.108, P<0.05), histological type ( χ2=11.270, P<0.05), and TRG grade after neoadjuvant chemotherapy ( χ2=6.797, P<0.05) were related to the success rate of organoidculture . Different from gastric cancer, the results of multivariate analysis of colorectal cancer showed that the histological type was an independent influencing factor ( P=0.018). Conclusions:The pathologic T stage, histological type of tumors, and TRG of cancer patients all have a significant impact on the success rate of establishing tumor organoids. Among them, the TRG grade is an independent influencing factor for the culture of gastric cancer organoids, and the histological type is an independent influencing factor for colorectal cancer organoids.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Dysregulation of immune response is currently recognized as one of the important pathological factors in ulcerative colitis (UC). Based on the confirmation that the Sini San (SNS) can significantly improve the colon inflammation induced by dextran sulfate sodium sulfate (DSS) in mice, the present work systematically studied the xenobiotics in the colon and mesenteric lymph nodes, spleen, and thymus of UC mice after administration of SNS by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry (HPLC-IT-TOF-MS). The results showed that, in addition to the colon, some components and their metabolites in SNS could be distributed in immune tissues, and it was found that the quality of relatively low-abundance and weakly responsive components such as saikosaponin a, paeoniflorin, and glycyrrhizic acid had the characteristics of efficient transmission to the colon and lymphoid organs. These components were very likely to be the source of pharmacodynamic substances of SNS. The findings of this study lay a foundation for the study of the efficacy and molecular mechanism of the components against ulcerative colitis, and also provide a scientific basis for the rational clinical application of SNS, which is expected to promote the secondary development of its preparations.