Objective To explore the role of ferroptosis-related genes in regulating ferroptosis of esophageal squamous cell carcinoma(ESCC).Methods ESCC datasets GSE161533 and GSE20347 were downloaded from the Gene Expression Omnibus(GEO)to identify the differentially expressed genes(DEGs)using R software.ESCC ferroptosis-related genes obtained by intersecting the DEGs with ferroptosis-related genes from FerrDb were analyzed using GO and KEGG analyses,protein-protein interaction(PPI)network analysis,and core gene identification through Cytoscape.The identified ferroptosis suppressor genes were validated using TCGA database,and their expression levels were detected using RT-qPCR in cultured normal esophageal cells and ESCC cells.Six ferroptosis suppressor genes(RRM2,GCLC,TFRC,TXN,SLC7A11,and EZH2)were downregulated with siRNA in ESCC cells,and the changes in cell proliferation and apoptosis were assessed with CCK8 assay and flow cytometry;Western blotting was performed to examine the changes in ferroptosis progression of the cells.Results We identified a total of 58 ESCC ferroptosis-related genes,which involved such biological processes as glutathione transmembrane transport,iron ion transport,and apoptosis and the ferroptosis,glutathione metabolism,and antifolate resistance pathways.The PPI network included 54 nodes and 74 edges with a clustering coefficient of 0.522 and PPI enrichment P<0.001.Cytoscape identified 6 core ferroptosis suppressor genes(RRM2,TFRC,TXN,EZH2,SLC7A11,and GCLC),which were highly expressed in ESCC tissues in the TCGA dataset and in ESCC cell lines.Downregulating these genes in ESCC TE1 cells significantly inhibited cell proliferation,promoted cell apoptosis,reduced the expression levels of ferroptosis markers GPX4 and FIH1,and increased the expression of ACSL4.Conclusion High expression of ferroptosis suppressor genes in ESCC may cause arrest of ferroptosis progression to facilitate tumor development,and inhibiting these genes can restore ferroptosis and promote cell apoptosis,suggesting their value as potential therapeutic targets for ESCC.

Objective:To analyze gene expression data of esophageal adenocarcinoma(EAC)in the Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)databases and clarify the relationship between the potential core genes and tumor lymphocyte infiltration in the EAC,and to provide the molecular targets for the diagnosis and treatment of EAC.Methods:The high-throughput chip datasets GSE13898,GSE26886,GSE74553,and GSE92396,including EAC and normal esophageal tissues,were downloaded from the GEO database by searching for"esophageal adenocarcinoma".The limma package of R software was used to screen the differentially expressed genes(DEGs)in EAC tissue and esophageal normal tissue,and the common DEGs were obtained through Venn diagram.After the DEGs were analyzed by STRING database,the results were imported into Cytoscape software to screen the core genes and construct the protein-protein interaction(PPI)network.The Gene Expression Profiling Interactive Analysis(GEPIA)database was used to verify the expression levels of core genes.The UALCAN and Kaplan-Meier Plotter databases were used to analyze the correlations between the core genes and prognosis and clinical data of the EAC patients.The Tumor Immune Estimation Resource(TIMER)database was used to analyze the relationship between core genes and tumor immune infiltration.Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed to analyze the positively correlated genes of core genes obtained from the LinkedOmics database.Results:A total of 340 DEGs were obtained from the intersection of DEGs from the four GEO datasets,including 127 upregulated genes and 213 downregulated genes.After screening with the STRING database and Cytoscape software,the key core genes with the highest scores were secreted phosphoprotein 1(SPP1)and transforming growth factor beta 1(TGFB1).The GEPIA database analysis results showed that compared with esophageal normal tissue,the expression levels of SPP1 and TGFB1 mRNA in cancer tissue were significantly increased(P＜0.01).The 1-year,3-year,and 5-year overall survival of the EAC patients in SPP1 low expression group was higher than those in SPP1 high expression group(HR=10.1,P＜0.05;HR=3.09,P＜0.05;HR=2.32,P＜0.05),and the 5-year overall survival of the EAC patients in TGFB1 low expression group was higher than that in TGFB1 high expression group(HR=2.36,P＜0.05).The UALCAN database analysis results showed that compared with esophageal normal tissue,the expression levels of SPP1 and TGFB1 mRNA in cancer tissue of the EAC patients with stage Ⅱ-Ⅲ and N1-N2 lymph node metastasis were significantly increased(P＜0.01).The TIMER analysis results showed that the expression levels of SPP1 and TGFB1 mRNA in cancer tissue of the EAC patients were positively correlated with the infiltration of macrophages(r=0.353,P＜0.01;r=0.187,P＜0.05)and dendritic cells(r=0.236,P＜0.01;r=0.221,P＜0.01).The GO and KEGG pathway enrichment analysis results showed that SPP1,TGFB1,and their top 50 positively correlated genes mainly participated in the biological processes such as cell migration,cell activity,and angiogenesis,and signaling pathways such as tumor proteoglycans,extracellular matrix(ECM)-receptor interaction,and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT).Conclusion:SPP1 and TGFB1 are closely associated with clinical staging,lymph node metastasis,and overall survival of the EAC patients.High expressions of SPP1 and TGFB1 may lead to the infiltration of the macrophages and dendritic cells,and change the tumor microenvironment.SPP1 and TGFB1 may become new targets for the diagnosis and treatment of EAC.

Objective To explore the role of ferroptosis-related genes in regulating ferroptosis of esophageal squamous cell carcinoma(ESCC).Methods ESCC datasets GSE161533 and GSE20347 were downloaded from the Gene Expression Omnibus(GEO)to identify the differentially expressed genes(DEGs)using R software.ESCC ferroptosis-related genes obtained by intersecting the DEGs with ferroptosis-related genes from FerrDb were analyzed using GO and KEGG analyses,protein-protein interaction(PPI)network analysis,and core gene identification through Cytoscape.The identified ferroptosis suppressor genes were validated using TCGA database,and their expression levels were detected using RT-qPCR in cultured normal esophageal cells and ESCC cells.Six ferroptosis suppressor genes(RRM2,GCLC,TFRC,TXN,SLC7A11,and EZH2)were downregulated with siRNA in ESCC cells,and the changes in cell proliferation and apoptosis were assessed with CCK8 assay and flow cytometry;Western blotting was performed to examine the changes in ferroptosis progression of the cells.Results We identified a total of 58 ESCC ferroptosis-related genes,which involved such biological processes as glutathione transmembrane transport,iron ion transport,and apoptosis and the ferroptosis,glutathione metabolism,and antifolate resistance pathways.The PPI network included 54 nodes and 74 edges with a clustering coefficient of 0.522 and PPI enrichment P<0.001.Cytoscape identified 6 core ferroptosis suppressor genes(RRM2,TFRC,TXN,EZH2,SLC7A11,and GCLC),which were highly expressed in ESCC tissues in the TCGA dataset and in ESCC cell lines.Downregulating these genes in ESCC TE1 cells significantly inhibited cell proliferation,promoted cell apoptosis,reduced the expression levels of ferroptosis markers GPX4 and FIH1,and increased the expression of ACSL4.Conclusion High expression of ferroptosis suppressor genes in ESCC may cause arrest of ferroptosis progression to facilitate tumor development,and inhibiting these genes can restore ferroptosis and promote cell apoptosis,suggesting their value as potential therapeutic targets for ESCC.

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

Objective To investigate the expression of Aire,Foxp3,AchR and other immune factors in human thymoma tissue and plasma and explore their role in myasthenia gravis with thymoma.Methods T lymphocyte subsets,immunoglobulin and other immune factors in plasma were compared,and the Expression of Aire,Foxp3 and AchR were examined in thymoma by reverse transcriptional polymerase chain reaction and immunohistochemical staining,and the results were analyzed by SPSS statistics software.Results The ratio of CD4 + to CD8 + T lymphocyte was much higher in plasma,while the expressions of Aire,Foxp3 and AchR at mRNA and protein level were much lower in thymoma patients with myasthenia gravis,and related to Ossermann subtype,WHO subgroup and Masaoka stage.The differences were statistically significant (P ＜ 0.05).Conclusion The ratio of CD4 + to CD8 + T lymphocyte and the abnormal expressions of Aire and Foxp3could used as an indicator of immune state in thymoma patient with myasthenia gravis and play an important role in the development of thymoma with myasthenia gravis,but the mechanism is indefinite.

Objective To evaluate the treatment of gastroentero-pancreatic neuroendcorine neoplasms with liver metastasis.Methods Two gastroentero-pancreatic neuroendcorine neoplasms with liver metastases treated at Anhui Provincial Hospital Affliated of Anhui Medical University were analyzed retrospectively.Results In first patient liver metastases from duodenal papilla neuroendocrine neoplasm was treated by four courses of TACE until the liver metastases completely disappeared.The patient then underwent pancreaticoduodenectomy to eradicate the primary tumor.The patient was followed up for 2 years and was doing well.In second patient, liver metastasis, noted four years after distal pancreatectomy for a neuroendocrine tumor, was initially managed by high dosage of octreotide and sunitinib.After these attempts failed, the patient received a liver transplantation four years ago and was followed up until March 1, 2015 without tumor recurrence.Conclusion Liver metastasis of gastroenteropancreatic neuroendcorine neoplasms responds positively to liver transplant with pretty good prognosis.

Objective To investigate the effect of the multimodal analgesia on postoperative pain after renal transplantation and the cytokines .Methods 40 cases of allogaft renal transplantation due to chronic renal failure were randomly divided into two groups (n=20) .The group D received the multimodal analgesia :preemptive analgesia plus patient controlled epidural analgesia(PCEA) and the group C(control) received analgesic drugs by intermittent intramuscular injection .The visual analogue scale(VAS) scores , the Ramsay sedation scores ,HR ,MAP and SPO2 at postoperative 2 ,6 ,12 ,24 ,48 h were recorded .Blood interleukin-2(IL-2) ,in-terleukin-6(IL-6) and interleukin-10(IL-10) levels were measured before anesthesia ,at the end of operation and postoperative 6 , 24 ,48 h .Results Postoperative MAP and SPO2 had no obvious change in the two groups ,no statistical differences in the various time points existed between the two groups (P>0 .05) .HR was significantly increased at 6 ,24 h after operation in the group C , which had statistical difference compared with that at the same time points in the group D (P<0 .05) .The VAS scores at postoper-ative 6 ,12 ,24 h in the group D were significantly lower than those in the group C ,the difference showed statistical significance (P<0 .05) .The sedation scores at various time points had no statistical difference between the two groups (P>0 .05) .The levels of IL-2 and IL-10 at postoperative 6 ,24 ,48 h in the two groups were significantly higher than those before anesthesia and at the end of operation (P<0 .05) .The levels of IL-2 and IL-6 at postoperative 6 ,24 ,48 h in the group D were significantly lower than those in the group C(P<0 .05) .Conclusion Multimodal analgesia can reach the effective analgesic effect ,down-regulate the pro-inflam-matory cytokines and up-regulate anti-inflammatory cytokines for maintaining postaperative serum cytokines balance .

BACKGROUND:Multimodal analgesia provides sufficient analgesia in renal recipients and appears to be associated with the recovery of renal function after transplantation. OBJECTIVE:To investigate the effect of multimodal analgesia with dezocine on postoperative immunity after renal transplantation, and discuss the appropriate analgesic drugs and methods for patients with renal transplantation. METHODS:Forty patients undergoing renal transplantation were randomly divided into two groups. They al received general anesthesia combined with epidural blockage. Control group received intramuscular injection of analgesic drugs when needed, while dezocine group received multimodal analgesia:preemptive anaIgesia with dezocine+patient-control ed epidural analgesia. The heart rate, mean arterial pressure, and saturation of blood oxygen were detected before anesthesia, 12, 24, 48 hours after transplantation. T lymphocyte subsets, interleukin-2, interleukin-6 and interleukin-10 levels in venous blood were measured before anesthesia, 12, 24, 48 hours after transplantation. RESULTS AND CONCLUSION:Compared with before anesthesia, the CD4+, CD8+cellsubset counts, CD4+/CD8+ratio, the levels of interleukin-2 and interleukin-6 were decreased significantly (P<0.05), and the levels of interleukin were significantly increased after transplantation in the control group (P<0.05). The postoperative CD4+cellsubset counts, the levels of interleukin-2 and interleukin-6 were significantly lower at 12 hours after transplantation than that before anesthesia (P<0.05), then recovered to normal levels at 24 hours in dezocine group. The postoperative CD8+cellsubset counts, CD8+and CD4+/CD8+ratio were not changed before and after transplantation in the dezocine group. The levels of interleukin-10 in the dezocine group were significantly increased at 48 hours after transplantation compared with before anesthesia (P<0.05), which was stil lower than that in control group (P<0.05). Multimodal analgesia with dezocine can effectively protect the immune system, promote short-term turnover of renal function, and prolong graft survival for patients with renal transplantation.

Objective To explore the effects and safety of endoscopic parallel placement of double metal stents on unresectable hilar malignant obstruction.Methods The clinical data of 11 patients with malignant hilar obstructive jaundice due to advanced carcinoma who were treated with parallel placement of double biliary stents from January 2011 to September 2012 were retrospectively analyzed.Results Out of 11 patients,10(90.9％) were successfully embedded with double biliary stents and 4 were dead during the follow-up.There was no sign of stent occlusion during the follow-up period.The survival time ranges from 128 to 185 days.One case was lost during the follow-up and 5 others are still alive.Conclusion The endoscopic parallel placement of double biliary stents is effective and safe for patients with unresectable malignant hilar obstruction.

ObjectiveTo explore the histopathological changes of bile duct,liver and local tissue for injurious biliary stricture(IBS). MethodTo observe the morphological and pathological changes of bile duct, local tissue and liver in different periods with dogs as the established animal model for IBS. ResultBile duct obstruction due to injury can expand the proximal bile duct up to 18.91 ±1.85 mm as the pressure goes up. Damage to local tissue triggers acute inflammation. In early injury phase (within 10 d), inflammatory cell infiltration and proliferation appears on the wall of the duct with increased mucosal edema as well as thickening of the biliary ductile wall. In the late injury phase (15 d), the degree of infiltration of inflammatory cells, edema and mucosal thickness were reduced whereas fibroblast and collagen tissue were proliferated extensively. The wall of biliary duct also becomes fibrotic and thickens. Quantitative analysis of the inflammatory edema shows the most severe outcome on the 5th day (HE staining WBC count of 54.2±5.8 unit) and its severity progressively subsides on the 15th day. (HE staining WBC count of 41.7±7.2 vs 54.2±5.8 a, P＜0.0,5). In the early obstruction (5 d and 10 d), the liver cells showed mild to moderate swelling and its degeneration is often associated with steatosis and sinusoidal expansion and congestion. As the obstruction time increases in the 20 d and 30 d group, liver cells starts to show extensive vacuolation and sinusoidal occlusion. ConclusionsEarly phase (5 days) of acute bile duct obstruction due to injury shows rapid expansion of the bile duct, edema in the bile duct itself as well as its surrounding tissue and liver damage. After 15 days, the local inflammatory edema is greatly reduced and is replaced by hyperplasia of fibers and collagen. Liver damage appears to be irreversible after 20 days. Considering local environmental and systemic conditions, the optimal time frame to repair obstruction of bile duct surgically is between 10-20 days.