Objective To explore the differential gene expression profile and small molecule drugs for chronic atrophic gastritis(CAG)by bioinformatics technology.Methods Two gene expression samples of CAG chips(GSE27411,GSE116312)were obtained through the Gene Expression Synthesis(GEO)database,screen the differentially expressed genes(DEGs)of CAG by R language,and CAG immune-related genes were obtained for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Protein-protein interaction(PPI)network was constructed using STRING database to screen out core genes,further study on immune invasion of core genes based on GSE27411 dataset,small molecular compounds interacting with core genes were predicted,molecular docking was carried out by MOE2022,and survival analysis was carried out by GEPIA2 website.Results A total of 517 DEGs were screened out based on GEO database.GO function enrichment analysis found that it mainly involved in granulocyte chemotaxis、leukocyte chemotaxis and neutrophil chemotaxis biological processes.KEGG pathway enrichment analysis showed that it mainly involved in cytokine-cytokine receptor interaction、nuclear factor kappa B signaling pathway、interleukin-17 signaling pathway.Six key genes of NR1H4、CCK、CCL20、CXCL1、LCN2、SAA1 were obtained by PPI network,through relevant verification,NR1H4 was regarded as the core gene.Immune cell infiltration analysis showed that central memory CD8 T cell、effector memeory CD4 T cell、gamma delta T cell、natural killer T cell、neutrophil and other immune cells may be involved in the development of CAG,and the neutrophil was positively correlated with NR1H4.It was predicted that six small molecular drugs,corilagin,stigmasterol,geniposide,tangeretin,chenodeoxycholic acid and epigallocatechin 3-gallate,have good binding force with NR1H4.Conclusion The potential mechanism of CAG is preliminarily explored in this study,the key gene of NR1H4 and neutrophil may play an important role in the"inflammatory cancer transformation"process of CAG,which can provide a certain reference for the study of the"inflammatory cancer transformation"mechanism of CAG.

The development, progression, and curative efficacy of head and neck squamous cell carcinoma (HNSCC) are influenced by complex interactions between epithelial and immune cells. Nevertheless, the specific changes in the nature of these interactions and their underlying molecular mechanisms in HNSCC are not yet fully understood. Cuproptosis, a form of programmed cell death that is dependent on copper, has been implicated in cancer pathogenesis. However, the understanding of cuproptosis in the context of HNSCC remains limited. In this study, we have discovered that cuproptosis-related long non-coding RNAs (CRLs) known as JPX play a role in promoting the expression of the oncogene urokinase-type plasminogen activator (PLAU) by competitively binding to miR-193b-3p in HNSCC. The increased activity of the JPX/miR-193b-3p/PLAU axis in malignant epithelial cells leads to enhanced cell proliferation, migration, and invasion in HNSCC. Moreover, the overexpression of PLAU in tumor epithelial cells facilitates its interaction with the receptor PLAUR, predominantly expressed on macrophages, thereby influencing the abnormal epithelial-immune interactome in HNSCC. Notably, the JPX inhibitor Axitinib and the PLAU inhibitor Palbociclib may not only exert their effects on the JPX/miR-193b-3p/PLAU axis that impacts the malignant tumor behaviors and the epithelial-immune cell interactions but also exhibit synergistic effects in terms of suppressing tumor cell growth and arresting cell cycle by targeting epidermal growth factor receptor (EGFR) and cyclin-dependent kinase (CDK4/6) for the treatment of HNSCC.
Humans ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Head and Neck Neoplasms/metabolism* ; Cell Proliferation ; Squamous Cell Carcinoma of Head and Neck/genetics* ; Urokinase-Type Plasminogen Activator/genetics* ; Cell Movement ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Carcinoma, Squamous Cell/genetics* ; Neoplasm Invasiveness

Objective: To investigate the effect and mechanism of renal fibrosis after macrophage depletion in C3-deficient unilateral ureteral obstruction mice. Methods: Renal interstitial fibrosis model was established by unilateral ureteral obstruction (UUO) in male C3-deficient mice and age-matched C57BL/6 WT mice (8-12 weeks of age). Mice were randomly divided into 4 groups, including sham operation in wild type group (WT/sham) (n=18), UUO operation in wild type group (WT/UUO) (n=18), sham operation in C3-deficient group (C3KO/sham) (n=18), and UUO operation in C3-deficient group (C3KO/UUO) (n=18). The expression of complement C3 was detected by immunohistochemical staining and renal interstitial macrophages were assessed by immunofluorescence staining. Tubulointerstitial fibrosis was observed by both HE staining and Masson staining after 14 days of UUO. Collagen accumulation and score of tubulointerstitial injury were obtained. Wild type and C3-deficient UUO mice were treated by liposome clodronate in early or late stage respectively and then interstitially infiltrated macrophages and renal fibrosis were analysed. Mice were sacrificed randomly at 3,7,14 days after UUO and obstructed kidneys were collected. Macrophage phenotype was detected by double-labeling immunofluorescence with F4/80 and iNOS for the M1, F4/80 and CD206 for the M2 macrophage subpopulation. iNOS, Arg-1 and CD206 were also detected by western blot. Results: C3 deficient mice exhibited attenuated renal fibrosis, reduced collagen accumulation and tubulointerstitial injury score compared with WT mice (P<0.01). Meanwhile, macrophage depletion in early or late stage of UUO reduced renal fibrosis in WT mice, but had no effect on C3-deficient UUO mice. Decreased accumulation of M1 macrophages and expression of iNOS, increased accumulation of M2 macrophages and expression of Arg-1, CD206 were found in C3 deficient mice compared with WT mice in early stage of UUO (P<0.01). Conclusion Renal fibrosis is not reduced after depletion of macrophages in C3 deficient UUO mice due to the altered macrophage polarization.

Objective To explore airway remodeling and air trapping in asthmatic patients with low dose CT scanning and quantitative analysis. Methods 52 stable asthmatic patients in which 29 were severe and 23 were slight,and 20 healthy control cases were underwent low dose dual phase CT scanning. The LA/BSA, WA/BSA, TA/BSA, WA%and Pi10WA were analyzed as airway remolding indexes. The MLD of expiratory, VI-850 (%) of expiratory, MLD E/I, VI-850E-I (%) and VI-850/-950E-I (%) were analyzed as air-trapping indexes. One-Way ANOVA or H Kruskal-Wallis was used to analyze the above indicators. Results Airway remodeling indexes and LA/BSA were (9.6 ± 2.6), (11.0 ± 3.4) and (12.6 ± 3.0)mm2/m2 in severe asthmatics group, non-severe asthmatics group and healthy control group respectively, and there was significant difference between the three groups (F=5.60, P=0.006). WA%of each group was (65.1 ± 2.5)%, (63.3 ± 4.4)%and (62.0 ± 3.0)%, and there was significant difference between the three groups (F=5.53,P=0.006). The Pi10WA was (18.4±2.6), (17.7±3.1) and (16.4±1.4) mm2 respectively with significant difference between the three groups (F=3.59 ,P=0.033). Air-trapping indexes, MLD of expiratory of each group was-(771 ± 59),-(724 ± 43) and-(676 ± 60) HU respectively with significant difference (F=5.60, P=0.006). VI-850(%) of expiratory of each group was 30.79(30.45)%, 13.53(12.09)%and 2.85(6.87)%respectively with significant difference (H=17.20,P<0.001). Conclusions Low dose of CT scan and quantitative analysis can provide an objective and quantitative information for patients with airway disease of asthma, and both WA% and Pi10WA were objective indexes. The severe asthmatic patients were associated with obvious airway remodeling and air trapping compared with non-severe asthmatic patients.

Objective To evaluate the application value with low-dose CT scan and quantitative analysis in airway disease of chronic obstructive pulmonary disease(COPD).Methods All subjects(34 control cases,88 cases of stable COPD patients)underwent low-dose CT chest scans,and 88 COPD patients underwent pulmonary function tests.Measuring the airway dimensions of 3th generation in apical bronchus of the right upper lobe,the posterior basal bronchus of the right lower lobe and left lower lobe.Results COPD patients with moderate to extremely severe airflow limitation demonstrated higher WA% and Pi10 in comparison with normal volunteers(all P<0.05),meanwhile patients with extremely severe airflow limitation demonstrated higher WA % and Pi10 in comparison with patients with mild airflow limitation(both P <0.05).COPD patients with severe airflow limitation demonstrated higher T/BSA and WA/BSA in comparison with normal volunteers and patients with moderate airflow limitation (all P<0.05).The WA % and Pi10 of COPD patients group were negatively correlated with ventilation indices and small airway indices(all P <0.01).Pi10 were positively correlated with lung volume indices (all P < 0.05 ).Conclusion Low-dose CT scan and quantitative analysis can provide an objective and quantitative method to evaluate the information about airway disease of COPD,inwich both WA % and Pi10 are objective indices.With the increase of air flow limitation,the bronchial wall thickness gradually increased.

Objective To explore the influence of different testing methods on detecting value of to-tal cell volume. Methods 60 reusable dialyzers(low-flux dialyzer and high-flux dialyzer were 30 respec-tively) were enrolled. They were divided into the traditional testing group, the modified testing group and the automatic dialyzer reuse group with 20 dialyzers in each group according to different detecting methods, the results underwent analysis. Results The basic total cell volume of the traditional testing group, the modified testing group and the automatic dialyzer reuse group were (100.10±0.25) ml, (100.13±0.50) ml and (102.00±1.41) ml in 6LR dialyzer, while in 17R dialyzer, they were (113.67±1.30) ml, (118.67±1.30) ml and (119.93±1.77)ml respectively. The total cell volume of the dialyzer reuse in the traditional testing group, the modified testing group and the automatic dialyzer reuse group were (95.20±7.76) ml, (96.20± 7.22) ml and (102.80±4.26) ml in 6LR dialyzer, while in 17R dialyzer, they were (100.00±11.48) ml, (114.35±3.31 ) ml and (117.07±2.96) ml respectively. There was significant difference between the tradi-tional and the modified testing groups in high-flux dialyzers reuse. Conclusions The modified testing method can improve the accuracy of the testing of total cell volume in high-flux dialyzer reuse.