Objective:To explore the value of the classifier model based on CT radiomic characteristics in predicting the activity of pulmonary cystic echinococcosis (CE).Methods:The study was designed as cross-sectional. A retrospective analysis was performed on 81 patients diagnosed with pulmonary CE in the First Affiliated Hospital of Xinjiang Medical University from January 2010 to October 2020. The Python function divided 17 cases into an internal verification group and 64 cases into a training group with a ratio of 2∶8. In addition, 16 patients diagnosed with pulmonary CE from the Fourth Affiliated Hospital of Xinjiang Medical University from October 2020 to 2024 were included in the external validation group. All patients underwent CT examination, and radiomics features were extracted using Radcloud platform of Huimedi Huiying. The intraclass correlation coefficient was performed on the features, then feature screening was performed using the SelectKBest method, variance thresholding method, and least absolute shrinkage and selection operator. Finally, three classifiers (including support vector machine (SVM), K-neighborhood (KNN), and logistic regression (LR)) were used to build the models. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the model′s efficiency.Results:Among 81 patients with lung CE, 58 were male, and 23 were female. twenty-eight lesions were active and 53 were inactive. A total of 11 optimal features were selected. Based on the selected features, the SVM classifier model, KNN classifier model, and LR classifier model were established. The KNN classifier model in the training group had the highest AUC value (0.93) and the highest specificity (0.98) in predicting lung CE activity. In the internal validation group, the SVM classifier model had the highest AUC value (0.92) and the highest specificity (0.91) in predicting lung CE activity. The LR classifier model performed best with the highest AUC of 0.85 for predicting lung CE activity in the external validation group, and the specificity of the three models was 0.92.Conclusion:The classifier model established based on CT radiomic features has a certain value in predicting lung CE activity, and may be helpful in clinical decision-making.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

OBJECTIVE：To study the effects of different amounts of Euphorbiae Semen fatty oil in self-assembly micelles on intestinal absorption of 4 kinds of euphorbia （euphorbia L 1，L2，L3，L8）in rats. METHODS ：The self-assembled micelle solution containing 4 kinds of euphorbia was prepared by adding 4 kinds of euphorbia （40 mg/L）in excess ，using the fatty oil of Euphorbia Semen（0.2，0.4，1，4 g/L）and sodium deoxycholate as carriers. Totally 60 rats were collected to establish in-situ one-way intestinal perfusion model. Different intestinal segments （duodenum，jejunum，ileum，colon）were perfused with drug-containing intestinal perfusion fluid according to different dosage of Euphorbiae Semen fatty oil. HPLC method was adopted to determine the contents of 4 kinds of euphorbia in the intestinal perfusate before and after perfusion. The absorption rate constant （Ka）and apparent absorption coefficient （Peff）of 4 kinds of euphorbia in different intestinal segments were calculated. The ileum segment with better absorption was selected as the object to investigate and calculate the ac cumulative absorption of 4 kinds of euphorbia. RESULTS：The self-assembled micelles formed by different concentrations of fatty oil of Euphorbiae Semen could significantly increase the absorption of 4 kinds of euphorbia in different intestinal segments to different extents. When the dosage of Euphorbiae Semen fatty oil was 0.4 g/L，the intestinal absorption effect of 4 kinds of euphorbia were all the best ；the Peff was significantly increased，compared with no fat oil group （P＜0.05 or P＜ . According to the order of Ka and Peff of each intestinal ： segment in different fatty oil dosage groups ，the absorption 0531-89628590。E-mail：1310394709@qq.com effect of 4 kinds of euphorbia in each intestinal segment was the best in jejunum and the worst in colon. Compared with no fatty oil group ，when the amount of Euphorbiae Semen fatty oil w as 0.2-4 g/L，accumulative amount of 4 kinds of euphorbia in the ileum of rats increased significantly （P＜0.05 or P＜0.01）， and the highest in 0.4 g/L Euphorbiae Semen fatty oil group. CONCLUSIONS ：The self-assembly micelle s composed of Euphorbiae Semen fatty oil and deoxycholate can increase the absorption of euphorbia L 1，L2，L3，L8 in each intestinal segment to different extent，and the jejunum is the main absorption segment.

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8 T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.
Adult ; Antigens, CD19 ; metabolism ; Bone Marrow ; metabolism ; CD8-Positive T-Lymphocytes ; immunology ; Female ; Gene Expression Regulation, Leukemic ; Gene Regulatory Networks ; Humans ; Immunotherapy, Adoptive ; Male ; MicroRNAs ; genetics ; metabolism ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; therapy ; RNA, Long Noncoding ; genetics ; metabolism ; Receptors, Antigen, T-Cell ; Transcription Factors ; metabolism ; Transcriptome ; genetics

Objective To investigate the effect and mechanism of astragalusⅣ (AS-Ⅳ) on the expression of CCL18in U937macrophages.Methods The expression of CCL18mRNA was detected by real time PCR.The expression of CCL18protein was assessed by Elisa.The expression of IL-4receptor was measured by flow cytometry.The STAT 6phosphorylation was measured by Elisa.The activity of JAK kinase was detected by Z″-LYTETMkinase assay.Results AS-Ⅳsignificantly down-regulated the expression of CCL18in U937macrophages stimulated by IL-4with a dose-dependent manner.However, AS-Ⅳhad no significant effect on IL-4receptor subunit expression.The STAT6phosphorylation was inhibited by AS-Ⅳ, but the effect was less than AS1517499;the activity of JAK1, JAK3and TYK2kinase were inhibited by AS-Ⅳ.Conclusion AS-Ⅳcould inhibit the expression of CCL18in U937macrophages stimulated by IL-4.One of the suggested mechanisms was due to inhibition of JAK kinase activity, which caused STAT6transcriptional activity down and inhibited CCL18gene expression.