ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.

Objective:To develop and validate a prediction model for medication adherence among patients receiving allergen sublingual immunotherapy (SLIT).Methods:A prospective cross-sectional study was conducted, and a total of 288 patients who received SLIT treatment at an allergy center in the First Affiliated Hospital with Nanjing Medical University (Jiangsu Province Hospital) from December 2023 to July 2024 were assigned to the modeling group. Additionally, 122 patients from August to October 2024 were assigned to the validation group. Data of patients′ general information, medication beliefs, anxiety levels, social support, disease perception, and medication adherence were collected. Single-factor analysis and LASSO regression were utilized to identify potential predictors, and a prediction model for medication adherence was constructed using multifactorial logistic regression. A nomogram was then developed based on the model. The model′s discriminatory ability was evaluated using receiver operating characteristic curve (ROC), the area under curve (AUC), sensitivity, and specificity. The model was then validated in the validation cohort.Results:Single-factor analysis and LASSO regression identified a total of nine predictive factors. Logistic regression revealed that medical belief tendency [ OR (95% CI) =2.420 (1.116-5.248), P=0.025], the somatic control dimension in self-rating anxiety scales [ OR (95% CI)=1.404 (1.241-1.589), P<0.001], the subjective support dimension in social support assessment [ OR (95% CI)=0.784 (0.725-0.847), P<0.001], and the cognitive dimension in illness perception [ OR (95% CI)=0.725 (0.647-0.813), P<0.001] were independent predictors of medication adherence in patients undergoing SLIT. The AUC value of the model was 0.899 (95% CI=0.863-0.934) in the modeling group and 0.882 (95% CI=0.820-0.944) in the validation group, indicating good discriminatory ability. The optimal cutoff value of the model was 0.493, with a sensitivity of 81.1% and specificity of 85.7% in the modeling group, and a sensitivity of 87.3% and specificity of 82.5% in the validation group. Conclusion:The medication adherence prediction model developed in this study for patients undergoing SLIT exhibits good predictive performance and provides valuable guidance for early intervention by clinical healthcare professionals.

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

Objective: To review the current development of artificial intelligence (AI) technology in the field of transfusion medicine. Methods: A systematic search was conducted in the Clarivate Web of Science Database from inception to December 2024 for literature related to AI and transfusion. A total of 4 775 publications were identified. Based on inclusion and exclusion criteria, 133 original studies were ultimately included and analyzed using a narrative synthesis approach. Results: Research on AI in transfusion has surged since 2020 (accounting for 77% of all publications), with China ranking second globally in publication volume. Among the included studies, 69.2% focused on predicting individual transfusion needs, followed by inventory management (8.3%), diagnosis and prediction of adverse transfusion reactions (6.0%), factors influencing transfusion outcomes (5.3%), blood group identification (5.3%), blood quality testing (4.5%), and precise blood volume measurement (1.5%). Additionally, 4.5% of the studies were published in journals with an impact factor greater than 10; 19.5% developed software or applications; 31.5% were multi-center studies; 48.1% utilized decision tree methods, while 31.5% employed neural network approaches; and 14.2% conducted external validation of the algorithms. Conclusion: AI demonstrates significant potential in transfusion risk prediction, decision support, and blood management. However, challenges remain, including limited model generalizability, insufficient algorithm interpretability, and barriers to clinical translation. The deep integration of AI with transfusion medicine will accelerate the advent of precision transfusion era, maximizing blood resource utilization, reducing waste, and ensuring transfusion safety.

This study was aimed at investigating the immunoregulatory function of Mycobacterium tuberculosis Rv3641c gene in modulating host type Ⅰ interferon responses.The shuttle plasmid pMV261 was used to construct Rv3641c overexpression recombinant Mycobacterium smegmatis,and the biological characteristics of the recombinant bacteria were analyzed to explore the effect of Rv3641c on the growth curve,colony morphology and stress resistance of Mycobacterium.Subsequently,RAW264.7 cells were infected with Rv3641c overexpressing Mycobacterium smegmatis,and the transcriptional expression of genes related to the inhibition of type I inter-feron pathway was determined by RT-PCR.The expression level of IFN-βprotein was determined by ELISA,and the intracellular sur-vival level was determined.As a result,the recombinant rMS::pMV261-Rv3641c was successfully constructed.The results of biologi-cal characteristics analysis showed that Rv3641c did not affect the growth of mycobacteria,but significantly changed the colony mor-phology of mycobacteria and improved its resistance to H2O2.The results of recombinant bacteria infection experiments showed that Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1β in host cells,and Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1βin host cells.The results of intracellular colonization experiments showed that the intracellular mycobacte-ria in the overexpression recombinant bacteria infection group were significantly higher than those in the empty vector group,indicat-ing that Rv3641c could promote the intracellular surviv al of mycobacteria.In summary,the Rv3641c gene of M.tuberculosis can inhibit the host type I interferon response and promote the intracellular survival of M.tuberculosis,which provides a new idea for further explor-ing the immune escape function of M.tuberculosis and the discovery of new targets for anti-tuberculosis drugs.

Objective To explore the mechanism of action of mitochondrial DNA(mtDNA)of alveolar epithelial type Ⅱ cells(AECⅡ)in silicotic fibrosis.Methods This study was divided into the animal experiment and cell experiment.Animal experiment:twenty-eight C57BL/6 mice were randomly divided into the saline group(n=14)and the silicosis model group(n=14),which were given 50 μL of sterile saline and 50 μL of 50 mg/mL of SiO2 suspension by tracheal perfusion respectively.HE staining and Masson staining were performed to observe the histopathological changes of mouse lung tissues after sampling with the exposure of 28 days and 56 days,and Western blot was used to detect the expression levels of functional proteins of pulmonary surfactant protein-D(SP-D),and Krebs von den Lungen-6(KL-6),and fibrotic protein of transforming growth factor-β1(TGF-β1)in mouse lung tissues.Cell experiment:AECⅡ cell line of A549 was exposed to different concentrations of SiO2 suspension.CCK-8 was used to detect cell viability,DAPI staining was used to observe cell apoptosis,Western blot was used to detect related protein expression,JC-1 was used to detect the changes of mitochondrial membrane potential,and RT-qPCR was used to detect mtDNA levels in whole cells,mitochondria,cytoplasm and supernatant.The expression levels of related proteins in AECⅡ were detected by Western blot after cleared mtDNA by DnaseⅠ.Results Histopathological examination of lung tissues showed that SiO2 exposure led to damage in mice lung tissues,with infiltration of inflammatory cell,silica nodules,and a significant increase of collagen fibers.After SiO2 exposure,the protein expressions of SP-D,KL-6 and TGF-β1 in lung tissues were up-regulated(P<0.05).DAPI staining and CCK-8 results showed a reduced activity and impaired apoptosis of AECⅡ after treated with 400 and 800 μg/mL SiO2.JC-1 assay results demonstrated that exposure to 800 μg/mL SiO2 caused a decrease of mitochondrial membrane potential in AECⅡ(P<0.05).RT-qPCR results showed that 800 μg/mL SiO2 exposure led to increased mtDNA levels in the cytoplasm and supernatant of AECⅡ(P<0.05).Western blot results showed that 800 μg/mL SiO2 exposure caused an increase in the levels of SP-D,KL-6,and TGF-β1 proteins,while which were ameliorated by Dnase Ⅰ treatment.Conclusion SiO2 exposure results in the escape and release of AECⅡ mtDNA and dysfunction of AECⅡ,thereby leading to the development of pulmonary fibrosis.

Virtual avatar possesses unique advantages such as high degree of realism,immersion and visualization,and the research on applying it to the assessment and treatment of anorexia nervosa is increasing year by year.In terms of assessment,there are mainly avatar versions of the figure rating scales,yes-no tasks and its variations,method of adjustment,and the use of virtual cylinder technique.In terms of treatment,there are mainly intervention methods based on virtual avatar exposure therapy,body swapping illusions,perceptual/attention training and self-empowerment,as well as some new potential interventions.Overall,the current research around anorexia nervosa using virtual avatar techniques is still in its early stages and there is still a lot of room for further exploration.