Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.

Objective: To understand relationship of positive and negative peer events with mental health problems among college students, so as to provide a scientific basis for improving mental health level of college students. Methods: A total of 1 640 freshmen to juniors were randomly selected from two universities in Anhui Province from October to November 2023 by a combination of convenience sampling and cluster random sampling method. The positive and negative peer events, self perceived loneliness and stress levels, anxiety and depression symptoms of students were investigated by using the questionnaire star online. Group comparisons were conducted by using analysis of variance and Chi square test, and multivariate binary Logistic regression and linear regression were used to analyze relationship of positive and negative peer events with mental health problems among college students. Results: About 35.4% of college students reported that they experienced at least one type of negative peer events, and 91.3% reported that they experienced at least one type of positive peer events. After controlling for covariates,multivariate regression analysis found that experiencing 1, ≥2 types of negative peer events were positively correlated with loneliness scores of college students ( β = 1.36,4.04), as well as an increased risk of anxiety symptoms ( OR =2.24,4.33) and depression symptoms ( OR =2.19,4.01); and experiencing ≥2 types of negative peer events was positively correlated with stress scores of college students ( β =1.12)( P <0.05). Experiencing 5-6 and 7 types of positive peer events were negatively correlated with loneliness scores of college students ( β = -1.79, -2.44) and stress ( β =-0.75, -1.12); and experiencing 7 types of positive peer events were associated with a lower risk of anxiety symptoms ( OR =0.74) and depressive symptoms ( OR =0.80) ( P <0.05). The number of negative peer events was positively correlated with loneliness scores ( β =0.80) and stress scores( β =0.24), as well as the risk of anxiety symptoms ( OR =1.30) and depressive symptoms ( OR =1.27) among college students ( P <0.05). The number of positive peer events involved was negatively correlated with loneliness scores( β =-0.39) and stress scores( β =-0.19), as well as the risk of anxiety ( OR =0.92) and depressive symptoms ( OR =0.93) among college students ( P <0.05). The analysis of the moderating effect found that in different groups of positive peer events, reporting 1, ≥2 negative peer events were positively correlated with loneliness scores of college students ( β=1.08- 4.96), as well as an increased risk of anxiety symptoms ( OR =1.79-6.20) and depression symptoms ( OR =1.78-6.77) ( P <0.05); and β and OR coefficients were highest in the group reporting 0-4 types of positive peer events, followed by the group reporting 5-6 types of positive peer events, with lowest coefficients in the group reporting 7 types of positive peer events. Conclusions Negative peer events are positively correlated with psychological problems in college students, and positive peer events are negatively correlated with mental health problems. Positive peer events could alleviate the impact of negative peer events on mental health problems.

Objective: Traumatic brain injury (TBI) patients often experience massive bleeding and require blood transfusion. However, the storage duration of the transfused blood may affect the prognosis of these patients. This study explored the influence of exosomes derived from fresh and aged blood on the prognosis of rats with TBI, so as to provide theoretical support for the blood transfusion management of TBI patients. Methods: Exosomes were isolated from red blood cell (RBC) suspensions stored for 1 week and 5 weeks using ultracentrifugation method. The size, morphology and surface markers of the exosomes were identified by nanoparticle flow cytometry, transmission electron microscopy and Western blotting, respectively. A rat model of TBI was constructed using a mechanical impactor for brain injury. After the successful establishment of the model, exosomes from RBC suspensions stored for 1 week and 5 weeks were injected into the extracellular space of rat brain cells using a stereotactic syringe. Cerebral edema at day 1, 3, 7 and 14 were recorded through cranial magnetic resonance imaging (MRI) scans. Magnetic tracing technology (the tracer was Gd-DTPA solution) was used to evaluate the drug metabolism level in the extracellular space of brain cells of TBI rats. The cranial magnetic resonance imaging was scanned every 15 or 30 minutes, and the recording lasted for a total of 240 minutes. The magnetic images were imported into the 3D-Slicer software in Dicom data format for analysis. Mass spectrometry technology was used to analyze the differential proteins of exosomes from RBC suspensions stored for 1 week and 5 weeks, and functional prediction was carried out to explore the possible mechanisms by which exosomes affect the prognosis of TBI. Results: After injection of exosomes into TBI rats, the areas of cerebral edema on the day 1, 3, 7, and 14 were all significantly higher in the rats treated with exosomes from 5-week-stored RBC suspensions, with peak cerebral edema occurring at day 3. The diffusion volume of the tracer was significantly higher in TBI rats than in normal rats, which implied there was a disorder in the structure of the traumatic brain tissue in TBI rats. Compared with the rats injected with exosomes from 1-week-stored RBC suspensions, those treated with exosomes from 5-week-stored RBC suspensions showed increased tracer diffusion volume within 120 minutes. Mass spectrometry analysis identified 81 differentially expressed proteins between exosomes from RBC suspensions stored for 5 weeks vs 1 week. Among them, 93.83% (76/81) proteins had increased expression levels. The neurodegeneration-related pathways were among the most enriched pathways for upregulated proteins. Conclusion: The exosomes from aged RBC suspensions can lead to exacerbated cerebral edema, disrupted extracellular space, and suppressed metabolic rate in TBI rats, suggesting that transfusion of aged RBC suspensions may have adverse effects on TBI patients.

Background High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker for cardiovascular disease (CVD) and can independently predict the risk of cardiovascular events. Although the association between per- and polyfluoroalkyl substances (PFAS) exposure and CVD risk has been widely reported, studies on the association between hs-CRP and PFAS remain limited. Objective To investigate the association between PFAS and hs-CRP levels, to provide a scientific basis for early identification and prevention of environment-related cardiovascular events. Methods This study utilized data from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018). Based on predefined inclusion and exclusion criteria, a total of 3219 participants were included for subsequent analysis. Five PFAS with detection rates exceeding 90% were selected as exposure factors and log-transformed (lnPFAS) for subsequent analysis, including perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA). After selecting potential confounders through a change-in-estimate approach, logistic regression was employed to examine the effects of individual PFAS on serum hs-CRP level. Additionally, quantile g-computation and Bayesian kernel machine regression (BKMR) were applied to assess the combined effects of PFAS mixtures on hs-CRP. Results The study included 3219 participants with a mean age of (50.4±17.6) years, of whom 1554 (48.28%) were male. The median concentrations of the five PFAS compounds were: 1.20 ng·mL⁻¹ (PFHxS), 0.50 ng·mL⁻¹ (PFNA), 1.50 ng·mL⁻¹ (PFOA), 5.20 ng·mL⁻¹ (PFOS), and 0.20 ng·mL⁻¹ (PFDA). The Wilcoxon rank-sum tests revealed statistically significant differences between the elevated serum hs-CRP (≥2 mg·L⁻¹) and normal (<2 mg·L⁻¹) groups for all five PFAS compounds (PFHxS: P=0.005; PFNA: P=0.009; PFOA: P<0.001; PFOS: P<0.001; PFDA: P<0.001). After adjusting for potential confounders, the analysis of individual PFAS exposure demonstrated significant negative associations between serum hs-CRP levels and both ln-PFOS (OR: 0.87; 95%CI: 0.79, 0.96; P=0.0036) and lnPFDA (OR: 0.78; 95%CI: 0.71, 0.86; P < 0.001). The joint effect analysis using quantile g-computation revealed an overall inverse association between PFAS mixtures and hs-CRP, with lnPFDA emerging as a primary contributor; an similar association was observed in males, but not significant in females. Further evaluation through BKMR showed that when PFAS mixture concentrations reached or exceeded P₇₀, their combined effect on hs-CRP became significantly lower than when all PFAS concentrations were at P₅₀, establishing a clear negative dose-response relationship. Conclusion The mixed exposure to PFAS showed a significant negative joint effect on serum hs-CRP levels, with PFDA being the key component contributing to this combined effect. Future prospective cohort studies are warranted to further validate these findings and elucidate the underlying mechanisms involved.

Objective To observe the value of SS-3DUNet model based on spatially separable convolutions for automatically segmenting anal fistula in enhanced MR T1WI.Methods Totally 2 405 pelvic axial enhanced MR T1WI of 29 patients with anal fistula were retrospectively analyzed,and 1 537 images from 19 cases were randomly selected as training set,424 images from 5 cases were as validation set,444 images from 5 cases were as test set.A SS-3DUNet model was constructed based on spatially separable convolutions to automatically segment anal fistula in enhanced MR T1WI,and inter-layer feature enhancement module was incorporated to improve the location of fistula features.The model was trained in training set and the best one was selected based on validation set.Taking the results of manual labeling by clinicians,the efficacy of SS-3DUNet model for automatically segmenting anal fistulas was observed based on test set.Results The time of SS-3DUNet automatically segmenting anal fistula in a single image in test set was 0.59-0.61 s,and the coincidence of the boundary of fistula segmented by the model and manual label was high.The average Dice similarity coefficient,sensitivity and accuracy of SS-3DUNet for automatically segmenting anal fistula in test set was 0.746,70.04%and 82.93%,respectively.Conclusion SS-3DUNet model based on spatially separable convolutions could effectively automatically segmenting anal fistula in enhanced T1WI.

Objective To investigate the mechanism of Sanguisorbae Radix(SR)in the treatment of ulcerative colitis(UC).Methods Using the GSE92415 dataset from the Gene Expression Omnibus database,we analyzed differentially expressed genes and carried out weighted gene correlation network analysis and FerrDb analysis.Core genes were identified through protein-protein interaction(PPI)network and correlation analysis.UC mouse model induced by dextran sulfate sodium(DSS)was constructed and treated with SR via intragastric administration for 9 days.Disease activity index(DAI)and colon length were recorded.Pathological changes in colon tissue were observed using the HE staining.Levels of inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay(ELISA).Lipid peroxidantion factors such as malondialdehyde(MDA)and glutathione(GSH)were detected using biochemical test kits.Protein expression levels of zonula occludens protein-1(ZO-1)tight junction protein,peroxisome proliferator-activated receptor gamma(PPARG),solute carrier family 7 member 11(SCL7A11),and glutathione peroxidase 4(GPX4)were examined by Western blot or immunofluorescence labeling.Results Nine differentially expressed genes associated with ferroptosis were screened and PPARG was identified as a key gene.Correlation analysis showed a strong correlation between PPARG and ferroptosis.Subsequently,the potential mechanism of SR in improving UC in mice was discussed according to the bioinformatics screening results.The experimental results demonstrated that SR significantly reduced the DAI,prevented colon shortening and improved intestinal mucosal barrier function in the colon.SR decreased TNF-α and IL-6 levels,MDA content and GSH levels in colon tissues.SR also enhanced the expression of PPARG,SLC7A11 and GPX4,which reversed the effect of DSS in mice with colitis.Conclusions Ferroptosis is closely related to UC.SR can inhibit ferroptosis by regulating PPARG and SCL7A11/GPX4 expression,thereby improving colon epithelial injury and dysfunction in UC mice.This provides ideas and directions for UC treatment strategies.

Objective:To establish a mesenchymal stem cell(MSC)-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease(aGVHD).Methods:Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors,and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients.The recipient mouse received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1× 107/mouse)in 6-8 hours post irradiation to establish a bone marrow transplantation(BMT)mouse model(n=20).In addition,the recipient mice received a lethal dose(8.0 Gy,72.76 cGy/min)of total body γ irradiation,and injected with donor mouse derived bone marrow cells(1 × 107/mouse)and spleen lymphocytes(2 × 106/mouse)in 6-8 hours post irradiation to establish a mouse aGVHD model(n=20).On the day 7 after modeling,the recipient mice were anesthetized and the blood was harvested post eyeball enucleation.The serum was collected by centrifugation.Mouse MSCs were isolated and cultured with the addition of 2％,5％,and 10％recipient serum from BMT group or aGVHD group respectively.The colony-forming unit-fibroblast(CFU-F)experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC.The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining.In addition,the expression of self-renewal-related genes including Oct-4,Sox-2,and Nanog in MSC was detected by real-time fluorescence quantitative PCR(RT-qPCR).Results:We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD.CFU-F assay showed that,on day 7 after the culture,compared with the BMT group,MSC colony formation ability of aGVHD serum concentrations groups of 2％and 5％was significantly reduced(P＜0.05);after the culture,at day 14,compared with the BMT group,MSC colony formation ability in different aGVHD serum concentration was significantly reduced(P＜0.05).The immunofluorescence staining showed that,compared with the BMT group,the proportion of MSC surface molecules CD29+and CD 105+cells was significantly dereased in the aGVHD serum concentration group(P＜0.05),the most significant difference was at a serum concentration of 10％(P＜0.001,P＜0.01).The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4,Sox-2,and Nanog was decreased,the most significant difference was observed at an aGVHD serum concentration of 10％(P＜0.01,P＜0.001,P＜0.001).Conclusion:By co-culturing different concentrations of mouse aGVHD serum and mouse MSC,we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability,which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Objective To develop the assessment scale of proactive health behavior ability for the disabled elderly in nursing homes and to test its reliability and validity.Methods The first draft of the scale was formed by literature review,qualitative interviews and Delphi method.From December 2023 to March 2024,525 disabled elderly people from 9 nursing homes in Sichuan Province and Chongqing City were selected as the survey subjects,and item analysis and reliability and validity test were carried out on the scale.30 disabled elderly people were re-investigated after 2 weeks to calculate the retest reliability of the scale.Results The scale consisted of 4 dimensions and 27 items.Exploratory factor analysis extracted 4 common factors,with the cumulative vanance contribution rate of 65.992％,and confirmatory factor analysis showed that the modified model fitting index was within acceptable range.The content validity index at item level was 0.917-1.000,and that at scale level was 0.997.The Cronbach's α coefficient,test-retest reliability and split-half reliability of the total scale were 0.944,0.997 and 0.882,respectively.Conclusion The scale has good reliability and validity,and it can be used to evaluate the proactive health behavior ability of the disabled elderly in nursing homes.

Objective:To analyze the application value of serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9 and CA242 in screening colorectal cancer with a meta-analysis.Methods:A literature search was conducted in the databases of Pubmed, Embase, Cochrane, CNKI, Wanfang and VIP to identify studies on applying CEA, CA19-9 and CA242 for detection of colorectal cancer from the establishment of the databases to October 2023. The Quality Evaluation Tool of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of the literature. Stata17.0 statistical software was used for meta-analysis. Deeks funnel plot was used to analyze publication bias.Results:A total of 34 articles of case-control studies met the criteria. Meta-analysis revealed that the diagnostic accuracy and sensitivity of CEA, CA19-9 and CA242 were all low, the area under the curve (AUC) of summary receiver operating characteristic curve was 0.62, 0.63 and 0.73, the sensitivity was 0.42, 0.27 and 0.36, respectively. The combined detection of CEA+CA19-9+CA242 significantly improved the pooled diagnostic accuracy (AUC: 0.92(95% CI: 0.89-0.94) and sensitivity: 0.75(95% CI: 0.65-0.83)), the specificity was mildly reduced (dropped from above 0.95 to 0.90(95% CI 0.87-0.93)). The Deek′s test indicated no publication bias. Conclusions:Combined detection of CEA+CA19-9+CA242 can significantly improve the diagnostic accuracy and sensitivity in screening colorectal cancer with a compromised specificity. However, due to the lack of data, whether it can meet the demand for opportunistic screening in the physical examination population needs to be confirmed.

Objective:To explore the application of biomechanics principle in the repair of double eyelid disappearance after blepharoplasty.Methods:A retrospective analysis was performed on 47 patients (46 females and 1 male) with double eyelid disappearance after blepharoplasty in the Department of Plastic and Cosmetic Surgery, Friendship Plastic Surgical Hospital from July 2018 to December 2022. The patients aged from 19-42 (28±8) years. The repair surgery was performed by increasing the mechanical factors that promoted the double eyelid formation or weakening the mechanical factors that inhibited the double eyelid formation. The overall satisfaction with ocular appearance, and psychological well-being and social function were evaluated with the Face-Q qustionnaires before or after operation.Results:By following-up for 3-24 months, the morphology of upper eyelids in all 47 patients were remarkably improved. 2 patients complained about asymmetry and 1 patient had multiple creases, for whom satisfactory results achieved after re-operation. The remaining patients presented smooth natural double eyelid line, and concave groove deformity when eyes closed were not noticed. The operative effects were satisfactory. After surgery, the scores for ocular satisfaction with facial appearance, psychological well-being and social function were (69.5±10.3), (75.5±13.6) and (68.3±11.3) scores, which were significantly increased than those before operation [(38.7±9.3), (54.8±10.5) and (52.3±8.7) scores], respectively (all P<0.05). Conclusion:More effective and reliable operation results can be obtained in the repair strategies of double eyelid disappearance after blepharoplasty by utilizing the biomechanical mechanism.