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关键词： 弥漫大B细胞淋巴瘤   主要组织相容性复合体   MHC I类分子   MHCⅡ类分子   临床病理特征  

摘要： 目的：本研究旨在探讨弥漫大B细胞淋巴瘤（diffuse Large B cell lymphoma， DLBCL）中主要组织相容性（major histocompatibility，MHC）复合体I、II表达及其与临床病理特征及预后的相关性。方法：收集新疆医科大学第一附属医院病理科DLBCL 130例，采用免疫组化EnVision法检测MHC-I、MHC-II蛋白表达情况，分析二者相关性及其与DLBCL临床病理特征和预后的关系。结果：（1）免疫组化染色结果显示，DLBCL肿瘤细胞中MHC-I、MHC-II低表达率分别为57.6%（68/118）和40.3%（48/119）。（2）MHC-I低表达与Ann-Arbor分期、PS评分、发生部位相关（P＜0.05），MHC-II低表达与年龄、结外受累病灶相关（P＜0.05），MHC-I/MHC-II共高表达与骨髓不易受累相关（P＜0.05）。（3）Kaplan—Meier单因素生存结果显示MHC-II低表达组预后差（P＜0.05），MHC-I对生存无显著影响（P＞0.05），多因素COX回归分析显示LDH、PS评分、IPI评分是影响DLBCL患者的独立危险因素。结论：MHC-I和MHC-II在DLBCL中低表达，与Ann-Arbor分期、PS评分、发生部位、年龄、结外受累病灶相关。MHC-II低表达的DLBCL患者预后较差。

摘要： Crystallization-induced asymmetric transformations can dramatically alter the product ratio from a reaction with inherently poor or undesired selectivity. Reported herein is a rare example of a dynamic crystallization-induced diastereoselective Strecker reaction which overrides the inherent substrate bias in the preparation of aryl-substituted tetrahydrofuran-derived non-natural amino acids. Discovery of a new non-hydrogenative auxiliary cleavage method enables application of the Strecker reaction to the large-scale syntheses of small molecule inhibitors of IL-17A.

关键词： chemokine   flagellin   lipopolysaccharide   rumen epithelium   short-chain fatty acids  

摘要： Objective:This study aimed to elucidate interleukin-1 beta (IL-1β) gene expression regulation and its function of defense mechanism in rumen epithelial cells of calves. Methods:Rumen tissues from six Holstein male calves were sampled at pre- (5 weeks of age, n = 3) and post-weaning (9 weeks of age, n = 3). IL-1β localization was analyzed using immunohistochemistry (IHC). Primary bovine rumen epithelial cells (BRECs) were treated with short-chain fatty acids (SCFAs), beta-hydroxybutyrate (BHBA), lactic acid, lipopolysaccharide (LPS), and flagellin, and IL-1β gene expression was analyzed by qRT-PCR. Additionally, bovine IL-1β-treated BRECs were assessed for cell proliferation, tight junction (TJ) protein expression, and chemokine mRNA expression. Results:IHC revealed IL-1β expression across all rumen epithelial layers. SCFAs, LPS, and flagellin significantly increased IL-1β mRNA expression (P < 0.05). Regarding the gene expression of rumen TJ proteins, CLDN4 and OCLN in suckling and weaned calves, as well as ZO-1 in weaned calves, showed significant decreases (P < 0.05), while CLDN1 in weaned calves showed a significant increase (P < 0.05) in IL-1β-treated BRECs. Regarding the gene expression of chemokines, the CCL2 expression significantly decreased (P < 0.05), while the CCL5 expression significantly increased (P < 0.05) in both suckling and weaned IL-1β treated BRECs. IL-1β treatment enhanced cell proliferation (P < 0.05). Conclusion:These results suggest that IL-1β induction by SCFAs, LPS, and flagellin, which increase in the rumen due to environmental changes, promotes cell proliferation in damaged rumen epithelium and contributes to its defense mechanism by upregulating CCL5 expression.

关键词： Acute exacerbation of bronchial asthma   Diagnostic value   ECP   FeNO   IL-4   Lung function   Periostin  

摘要： OBJECTIVE:This study aimed to analyze the diagnostic value of fractional exhaled nitric oxide (FeNO), periostin, interleukin (IL)-4, and eosinophil cationic protein (ECP) in patients with acute exacerbation of bronchial asthma (AEBA) and their relationship with lung function. METHODS:Ninety-six bronchial asthma patients admitted to our hospital from January 2020 to January 2021 were collected and divided into two groups: acute exacerbation group (n = 55) and non-acute-exacerbation group (n = 41). Pulmonary function indices and serum levels of FeNO, IL-4, periostin, ECP, and EOS% were determined. Pearson correlation analysis was used to analyze the relationships between these biomarkers and pulmonary function indices. A receiver operating characteristic (ROC) curve was applied to assess the diagnostic value of these biomarkers for AEBA. RESULTS:The acute-exacerbation group showed lower percentage of predicted values of peak expiratory flow (PEF%pred), forced expiratory volume in 1 second (FEV1%pred), and forced vital capacity (FVC%pred) while higher levels of FeNO, IL-4, periostin, ECP, and EOS compared to the non-acute-exacerbation group. Pearson correlation analysis indicated that FeNO, IL-4, periostin, and ECP levels were negatively correlated with PEF%pred, FEV1%pred, and FVC%pred, and positively correlated with EOS%. ROC curve analysis revealed that these biomarkers had high predictive value for AEBA. CONCLUSION:FeNO, IL-4, periostin, and ECP levels are negatively correlated with pulmonary function indices (PEF%pred, FEV1%pred, and FVC%pred) and positively correlated with EOS%. These biomarkers have high predictive value for AEBA.

关键词： disitamab vedotin   RC48   bladder cancer   TNF signaling pathway   NF-kappa B signaling pathway  

摘要： Disitamab Vedotin has shown good therapeutic efficacy against bladder cancer. Although its mechanism is clear, the regulation of gene expression in bladder cancer cells by Disitamab Vedotin is not fully understood. We searched the GEO database and identified the GSE237789 dataset, in which researchers treated the bladder cancer cell line SW780 with Disitamab Vedotin and performed high-throughput transcriptome sequencing. Compared with the control SW780 cells, the expression levels of the vast majority of genes (16,223/16,390, 98.98%) in Disitamab Vedotin-treated SW780 cells remained unchanged. Only one hundred fifty-nine genes (0.97%) were upregulated, and eight genes (0.05%) were downregulated. Enrichment analysis results showed that the related differentially expressed genes (DEGs) were mainly enriched in the TNF signaling pathway, NF-kappa B signaling pathway, and other pathways. Protein-protein interaction analysis revealed that 10 genes, TNF, IL1B, IL1A, CXCL8, CXCL1, CCL2, MMP9, ICAM1, CXCL10, and CCL20, had the highest connectivity, and all of these genes belong to the TNF signaling pathway. These results suggest that the TNF signaling pathway is the key pathway regulated by Disitamab Vedotin in bladder cancer cells, which may represent a stress response of bladder cancer cells to Disitamab Vedotin.

关键词： 4-dimensional computed tomography   heterogeneity   interleukin-6   mechanical ventilation   X-ray velocimetry  

摘要： This study aimed to characterize how peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) influence regional lung volume heterogeneity as a result of mechanical ventilation and the influence of this heterogeneity on markers of inflammation within the lungs. Four groups of BALB/C mice (n = 7 or 8 per group) were mechanically ventilated for 2 h using low or high (12 cmH(2)O or 20 cmH(2)O) peak inspiratory pressure (PIP) with or without 2 cmH(2)O positive end-expiratory pressure (PEEP). Four-dimensional computed tomography (4-DCT) images were acquired using synchrotron-based radiation source at baseline and after 2 h. Regional tidal volumes were obtained by 4-D cross-correlational X-ray velocimetry, whereas end-expiratory volume was quantified by Hounsfield units. Tissue was harvested from 10 lung regions, and expression of IL-6 and monocyte chemo-attractant protein 1 (MCP-1) was quantified using qPCR. We found a significant reduction in specific end-expiratory volume (sEEV) in mice ventilated with low PIP and no PEEP and a reduction in tidal volume in groups without PEEP. End-expiratory volume heterogeneity decreased in the low PIP and no PEEP group, whereas tidal volume heterogeneity decreased in the equivalent high PIP group, potentially due to regional redistribution of lung volumes. We found associations between IL-6 expression and tidal volume heterogeneity. In this study, we have demonstrated that changes in PIP and PEEP impact atelectasis, overdistension, and heterogeneity, and that increases in tidal volume heterogeneity may be driving IL-6-mediated biotrauma. These findings highlight the importance of considering the spatial distribution of tidal volumes as a driver of lung injury during mechanical ventilation. NEW & NOTEWORTHY The combination of low inspiratory and expiratory pressure promotes atelectasis but is not associated with markers of injury in the healthy lung during short-term ventilation. High inspiratory pressures promote t

关键词： Fluoxetine   Treatment-resistance   IL-17   JAK1-STAT6 signaling pathway  

摘要： Aims: This study aims to investigate the role of IL-17 in fluoxetine resistance in depression. Methods: The Weighted Gene Coexpression Network Analysis (WGCNA) was utilized to analyze differentially expressed genes between response to antidepressant (GRA) group and the resistance to antidepressant (AR) group. Furthermore, a treatment resistance model of depression was established in Chronic unpredictable mild stress (CUMS) mice administrated with fluoxetine (widely used clinical medication for the treatment of depression) according to sucrose preference rate. Depression-like behaviors in mice were detected in Control group, CUMS group, GRA group, AR group, and SR1001 (Th17 differentiation inhibitor) group. Subsequently, HT22 cells were exposed to IL-17 secreted by Th17 differentiation. Transcriptome sequencing from the Control and IL-17 group was used to screen differential genes. HT22 cells were then transfected with si-JAK1 or si-STAT6. Th17 differentiation, the integrity of the blood-brain barrier (BBB), JAK1-STAT6 signaling pathway related proteins were detected by western blot, immunocytochemistry, flow cytometric analysis, ELISA experiments, immunofluorescence, and PCR. Result: The WGCNA showed that Th17 differentiation played an important role in the treatment resistance of depression. The results of the following animal experiments showed that fluoxetine resistance resulted in a reduction in total distance and average speed in the Open Field Test (OFT), an increase in immobility time during the Forced Swim Test (FST) and Tail Suspension Test (TST). It also regulated the expression of the SERT protein, Th17 differentiation, IL-17 secretion, and compromised the integrity of BBB, yielding similar outcomes in CUMS mice. However, these results could be reversed by SR1001. Moreover, IL-17 effectively elevated the SERT protein level and activated the JAK1-STAT6 signaling pathway in vivo and in vitro.