Objective:To evaluate the early diagnostic value of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) in acute kidney injury induced by sepsis.Methods:A total of 85 sepsis patients admitted to the EICU and GICU in Shanghai East Hospital from September 2017 to June 2019 were divided into theAKI group ( n=37) and the non-AKI group ( n=48) according to KIDGO diagnostic criteria, and 20 healthy volunteers were served as the control group. The clinical data were recorded and samples of urine were collected at 0 h, 6 h, 12 h, 1 d, 3 d and 7 d post sepsis. The levels of TIMP-2 and IGFBP-7 in the urine were analyzed with ELISA at different time points. Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC), the early diagnostic value of urinary TIMP-2 and IGFBP-7 in sepsis-induced AKI patients was determined. Results:Compared with the control group, the levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher at the above time points ( P<0.05), while those of the non-AKI group showed no significant differences. The levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher than the those of the non-AKI group ( P<0.05). ROC analysis showed that when the AUC of urine TIMP-2 peaked at 1 d, the sensitivity and specificity reached 97.5% and 81.2%, separately with the cutoff value of 151.23 ng/mL. Furthermore, when the AUC of urine IGFBP-7 peaked at 12 h, the sensitivity and specificity reached 100% and 72.8%, separately with the cutoff value of 14.91 ng/mL. Interestingly, when the AUC of combined TIMP-2×IGFBP-7 peaked at 12 h, the sensitivity reached 98.0% and specificity reached 91.5% with the cutoff value of 2.09 [(ng/mL) 2/1 000]. There was no significant correlation between the levels of TIMP-2 and IGFBP-7 with SOFA and APACHEⅡ score at 1 d, 3 d and 7 d post sepsis in the AKI group ( P>0.05). Conclusions:Urine TIMP-2 and IGFBP-7 have early diagnostic value in sepsis-induced AKI. Besides, the combination of the two biomarkers have superior predictive value than each single of them.

Objective To explore the expression of prohibitin(PHB)in tumor tissues and analyze its effect on the prognosis of patients with digestive system malignant tumor(DT)and its mechanism.Methods ①The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)database were used to compare the expression of PHB in tumor tissues and normal tissues.②Five pairs of gastric cancer and adjacent tissues and 5 pairs of colon cancer and adjacent tissues were collected,and RT-qPCR was used to verify the mRNA expression levels.③ RT-qPCR and Western blotting were used to verify the differential expression of PHB in normal gastric mucosa cells(GES-1),gastric cancer cells(AGS,MKN45 and HGC27),normal colon cells NCM-460 and human colon cancer cell line SW480.④R language was used to analyze the effect of PHB on the prognosis,tumor microenvironment,tumor mutation burden and microsatellite instability of DT patients.⑤CIBERSORT algorithm was used to study the correlation between PHB expression in tumor tissues and tumor immune cell infiltration.Gene Set Enrichment Analysis(GSEA)was used to explore the biological function of PHB.⑥R language was used to analyze the relationship between PHB and drug sensitivity.Results ①PHB was highly expressed in colon cancer,cholangiocarcinoma,esophageal cancer,liver cancer,rectal cancer and gastric cancer(P＜0.01).②RT-qPCR and Western blotting showed that PHB was highly expressed in the tissues and cell lines of gastric cancer(P＜0.01)and colon cancer(P＜0.01).③The differential expression of PHB was associated with poor prognosis of hepatocellular carcinoma(P=0.002).In cholangiocarcinoma,gastric cancer,pancreatic cancer,liver cancer and esophageal cancer,PHB was positively correlated with tumor mutation burden and microsatellite instability(P＜0.05).④PHB was positively correlated with M2 macrophages in colon cancer(P=0.03).In cholangiocarcinoma,it was positively correlated with activated CD4+memory T cells(P＜0.05).In esophageal carcinoma,it was positively correlated with activated hypertrophy(P=0.03).It was positively correlated with M0 and M2 macrophages and monocytes in hepatocellular carcinoma(P＜0.05).It was positively correlated with resting dendritic cells,eosinophils and activated CD4+memory T cells in rectal cancer(P＜0.05).It was positively correlated with M0 macrophages,activated mast cells,neutrophils,resting natural killer cells,activated CD4+memory T cells and follicular helper T cells in gastric cancer(P＜0.05).⑤PHB was mainly enriched in class I receptors,PPAR and calcium signaling pathways(P＜0.05).⑥ The expression of PHB was positively correlated with the sensitivity of 13 drugs,including ammonafide,prasinolide and abiraterone(P＜0.05).Conclusion The expression of PHB is significantly related to the infiltration of various immune cells in DT and poor prognosis in DT patients,which may become a new biomarker and potential immunomodulatory target of DT.

Objective To investigate the expression of FBXO43in various cancers and its relationship with immune cell infiltration and prognosis using bioinformatics.Methods Gene expression data for 33 cancers were obtained from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases to analyze FBXO43expression.Clinical and survival data were sourced from the TCGA database.Gene Expression Profiling Interactive Analysis(GEPIA)was used to assess the correlation between FBXO43expression and the clinical stage.Kaplan-Meier survival analysis was used to evaluate the relationship between FBXO43expression and prognosis.R lan-guage was used to analyze the associations between FBXO43expression and clinical stages,immune cell infiltration,immune checkpoint genes,tumor mutation burden(TMB),microsatellite instability(MSI),and mismatch repair(MMR)genes.The potential biological mech-anisms of FBXO43were explored using gene set enrichment analysis(GSEA).Moreover,qRT-PCR was performed to measure FBXO43 expression in normal gastric mucosal cells(GES-1),gastric cancer cells(HGC-27,MGC-803,and MKN-45),normal liver cells(LO-2),and liver cancer cells(SMMC-7721,HEPG2,HuH7,and MHCC97-H).Results Combined TCGA and GTEx database statistics revealed higher FBXO43expression in 26 types of cancer tissues,including adrenocortical carcinoma(ACC),bladder urothelial carcinoma,breast invasive carcinoma,cervical squamous cell carcinoma and endocervical adenocarcinoma,cholangiocarcinoma,colon adenocarcinoma,and diffuse large B-cell lymphoma,than in normal tissues(P<0.05).However,FBXO43expression was lower in three types of cancer tissues:kidney chromophobe(KICH),testicular germ cell tumor(TGCT),and thyroid carcinoma(P<0.05).GEPIA data analysis showed that FBXO43expression positively correlated with the clinical stages of ACC,KICH,kidney renal clear cell carcinoma(KIRC),and kidney renal papillary cell carcinoma(KIRP)and negatively correlated with the clinical stages of ovarian serous cystadenocarcinoma(OV)and TGCT(P<0.05).Kaplan-Meier survival analysis indicated that abnormal FBXO43expression was associated with the prognosis of various cancers(P<0.05).Specifically,high FBXO43expression was a risk factor for ACC,KICH,KIRC,KIRP,low-grade glioma,liver hepato-cellular carcinoma,mesothelioma,and sarcoma,but protective in thymoma(THYM).The XCELL algorithm found that FBXO43expres-sion was negatively correlated with immune scores in nine types of cancer tissues,including glioblastoma multiforme,KIRP,acute myeloid leukemia,lung squamous cell carcinoma,and OV,and closely related to immune cell infiltration levels in 24 types of cancer tissues,espe-cially showing a significant negative correlation with most immune cells in SARC(P<0.01).Correlation analysis revealed a significant association between FBXO43and TMB,MSI,and MMR in all cancers.GSEA analysis indicated that FBXO43is involved in the cell cycle and immune-related functions in various tumors.qRT-PCR results showed that FBXO43expression was upregulated in liver cancer cells and downregulated in gastric cancer cells(all P<0.05).Conclusion Abnormal FBXO43expression is closely associated with the occur-rence and progression of multiple cancers.Thus,FBXO43may serve as a novel marker of immune cell infiltration and prognosis,thereby offering new directions for targeted cancer therapy.

Objective To analyze the core genes of lung ischemia-reperfusion injury and construct a competitive endogenous RNA (ceRNA) network. Methods Original data of GSE145989 were downloaded from the Gene Expression Omnibus (GEO) database as the training set, and the GSE172222 and GSE9634 datasets were used as the validation sets, and the differentially-expressed genes (DEG) were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed, and the core genes were screened, and the diagnostic values of these core genes and the immune infiltration levels of immune cells were evaluated. The ceRNA network was constructed and validated. The targeted drugs based on ceRNA network were assessed. Results A total of 179 DEG were identified, including 61 down-regulated and 118 up-regulated genes. GO analysis showed that DEGs were associated with multiple biological processes, such as cell migration, differentiation and regulation, etc. They were correlated with cell components, such as vesicle membrane, serosa and membrane raft, etc. They were also associated with multiple molecular functions, such as chemokine receptor, G protein-coupled receptor, immune receptor activity and antigen binding, etc. KEGG pathway enrichment analysis revealed that DEG were involved in tumor necrosis factor (TNF), Wnt, interleukin (IL)-17 and nuclear factor (NF)-κB signaling pathways, etc. PPI network suggested that CD8A, IL2RG, STAT1, CD3G and SYK were the core genes of lung ischemia-reperfusion injury. The ceRNA network prompted that miR-146a-3p, miR-28-5p and miR-593-3p were related to the expression level of CD3G. The miR-149-3p, miR-342-5p, miR-873-5p and miR-491-5p were correlated with the expression level of IL-2RG. The miR-194-3p, miR-512-3p, miR-377-3p and miR-590-3p were associated with the expression level of SYK. The miR-590-3p and miR-875-3p were related to the expression level of CD8A. The miR-143-5p, miR-1231, miR-590-3p and miR-875-3p were associated with the expression level of STAT1. There were 13 targeted drugs for CD3G, 4 targeted drugs for IL-2RG, 28 targeted drugs for SYK and 3 targeted drugs for lncRNA MUC2. No targeted drugs were identified for CD8A, STAT1 and other ceRNA network genes. Conclusions CD8A, IL2RG, STAT1, CD3G and SYK are the core genes of lung ischemia-reperfusion injury. The research and analysis of these core genes probably contribute to the diagnosis of lung ischemia-reperfusion injury and providing novel research ideas and therapeutic targets.

Digestive tract tumors are currently one of the most common types of cancer,including esophageal cancer,gastric cancer,hepatocellular carcinoma,pancreatic cancer,and colorectal cancer.Their prognoses are poor and the treatments require further improvement.Caveolin-1(CAV1)has a dual regulatory effect on digestive tract tumors as a tumor suppressor and cancer promoter.CAV 1 plays a major role in cell proliferation,invasion,metastasis,angiogenesis,and drug tolerance of digestive tract tumors.The regulation of CAV1 protein and its related signaling pathways may be a strategy for the treatment of digestive tract tumors.This review analyzes the relationship between CAV 1 and digestive tract tumors in terms of structure,function,expression regulation,regulation of epithelial-mesenchymal transition,and drug resistance in digestive tract tumors to provide new ideas for the diagnosis and treatment of digestive tract tumors.

Objective To screen long non-coding RNA(lncRNA)associated with disulfidptosis and investigate the immune landscape between lncRNA and pancreatic cancer,for effective guidance in clinical practice.Methods The normal and pancreatic cancer tissue samples were obtained from The Cancer Genome Atlas database,and the lncRNA associated with disulfidptosis was identified based on the Cox and LASSO regression analyses.A risk prognosis model was constructed,and its predictive performance was verified using comprehensive methods.An accurate nomogram was construted to predict the prognosis of patients with pancreatic cancer.The biological differences were analyzed via Gene Ontology,Gene Set Enrichment Analysis,and an immunoassay.The immunotherapy response was estimated using the tumor mutational burden(TMB)score.Results A total of 251 disulfidptosis-related lncRNAs were successfully identified,and three groups of lncRNAs were selected as the reference for the risk model.Pathway analysis showed that immune-related pathways were associated with disulfidptosis-related lncRNA risk models.The risk score was significantly correlated with immune cell infiltration and the ESTIMATE score.Patients with higher risk scores had elevated TMB,indicating that high-risk patients exhibited a better immune checkpoint blockade response.Conclusion The findings of this study contribute to a deeper understanding of disulfidpto-sis-related lncRNA and provide a potential therapeutic strategy for pancreatic cancer.

Objective To investigate the expression of CD276 in pan-cancer,its effect on patient prognosis,and its mechanism of action.Methods TCGA and GTEx databases were used to study the differential expression of CD276 in tumor and normal tissues;R language was used to analyze the effects of CD276 on the prognosis of patients with pan-cancer,the tumor microenvironment,the tumor mutation burden,and microsatellite instability;the correlation between the expression of CD276 in tumor tissues and the tumor immune cell infil-tration was further examined;the biological function of CD276 was analyzed using Gene Set Enrichment Analysis(GSEA);and finally,real-time PCR was used to validate the expression of CD276 in tumors in vitro.Results A statistical difference in CD276 expression was detected between tumor and normal tissues(P<0.05).CD276 affects tumor prognosis and is strongly associated with the tumor microenvi-ronment,tumor mutational burden,microsatellite instability,and tumor immune cell infiltration.Conclusion Comprehensive pan-cancer analysis identified CD276 as a biomarker for immune infiltration and poor cancer prognosis,which can be used as a novel immunomodula-tory target for the development of immunotherapeutically-targeted drugs,providing new ideas for tumor therapy.