Esophageal cancer related gene 4 (ECRG4) serves as a tumor suppressor gene through interacting with NF-κB and p53 pathways.Multiple studies have demonstrated that the down-regulated expression of ECRG4 occurs in a variety of cancer types,indicating a potential application of ECRG4 as a molecular diagnostic marker as well as a therapeutic target

Objective To examine the inhibition effect of zoledronic acid (ZOL) on malignant metastasis of human esophagus squamous cell carcinoma (ESCC) cells and to analyze its molecular mechanisms.Methods EC9706 and EC109 cells were treated with ZOL,and then MTT assay,adhesion and invasion assay were performed to observe the inhibitory effect of As2O3 on proliferation and metastasis of esophagus carcinoma cells.The expression of metastasis-related proteins was detected by Western blotting.Results Exposure to ZOL significantly presented suppressive functions on growth and metastasis of both kinds of cancer cells,in a dose-dependent manner(P＜ 0.05).Additionally,the expression level of occludin was increased after ZOL treatment by suppressing transcriptional factor Slug.Transfection of Slug could reverse anti-metastasis of ZOL.Conclusion ZOL possesses a significant anti-metastasis function on ESCC cells,mainly through repressing Slug to restore occludin expression.

Cyclin-dependent kinase 10 (CDK10) function as a tumor suppressor gene through regulating cell cycle interacting with transcription factor Ets2.Studies demonstrate that the downregulation of CDK10 expression occurs in multiple cancer types,indicating a potential application of CDK10 as a molecular diagnostic marker as well as therapeutic target.

Objective:To discuss the level changes and significance of IL-2,IFN-γ,TNF-α in patients with bladder cancer.Methods:66 patients with bladder cancer who were treated in our hospital from February 2015 to December 2016 were enrolled in this study,which was denoted by bladder cancer group,65 patients with cystitis glandularis who were treated in our hospital during the same period were selected as cystitis group,another 65 healthy persons who were examined in our hospital during the same period were selected as control group,and compared the levels of IL-2,IFN-γ and TNF-α in each group,and the levels of IL-2,IFN-γand TNF-α in patients with bladder cancer of different types and clinical stages.The correlation of IL-2,IFN-γ and TNF-α levels with pathological types and clinical stages were analyzed.Results:The levels ofIL-2 and INF-γ in bladder cancer group were significantly lower than those in cystitis group and control group,the level of TNF-α was significantly higher than that of cystitis group and control group,the difference was statistically significant (P＜0.05).There was no significant difference in IL-2,IFN-γ and TNF-α levels in different types of bladder cancer patients (both P＞0.05).IL-2,IFN-γ levels in T2 to T4 bladder cancer patients were significantly lower than Tis to T1,TNF-α level was significantly higher than Tis to T1,the difference was statistically significant (both P＜0.05).According to Spearman method evaluation correlation founded that IL-2,IFN-γlevels in patients with bladder cancer were negatively correlated with clinical stage,TNF-α level was positively correlated with clinical stage.However,there was no correlation between IL-2,IFN-γ and TNF-α levels in patients with pathological type.Conclusion:IL-2,IFN-γ expression in bladder cancer patients are decreased significantly,while TNF-α expression is increased significantly,and the above three indexes of patients are related to clinical stage,but not related to pathological type.

Objective To investigate the molecular mechanism of As 2 O3 in suppressing metastasis of esophagus carcinoma cells.Methods The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, adhesion and invasion assay were performed to observe the inhibitory effect of As 2 O3 on proliferation and metastasis of esophagus carcinoma cells .The expressions of matrix metalloproteinases ( MMP)2, MMP9, E-cadherin, and protein tyrosine phosphatase receptor-type O ( PTPRO) were analyzed with Western blot .Results Exposure to As 2 O3 significantly presented suppressive functions on growth and metastasis of esophagus carcinoma cells in a dose-dependent manner ( P <0.01 ) .Additionally , MMP2 and MMP9 expressions were increased after treatment with casticin ( P <0.01 ) , whereas E-cadherin and PTPRO expressions were down-regulated ( P <0.01 ) .Conclusions As2 O3 had a significant function to inhibit proliferation and metastasis of esophagus carcinoma cells .

ObjectiveTo examine the expressions of amplified in breast cancer 1(AIB1) and epithelial cadherin (E-cadherin) in ovarian carcinoma (OC) tissues,and determine the correlation between the expression and clinical pathological features.MethodsThe expression of AIB 1,E-cadherin,estrogen receptor (ER),progesterone receptor (PR) and Ki-67 in tissues of 50OCs and 13 normal ovarians tissues were detected by immunohistochemistry(IHC) EnVision two step process analysis.ResultsPositive expression of AIB1 in OC tissues[68％(34/50) ] was obviously higher than that in normal ovarian tissues [8％ (1/13)] (P ＜0.01).Down-regulation of E-cadherin expression was 60％ (30/50).The positive expression of AIB1 was significantly higher in stage Ⅲ and Ⅳ than in stage Ⅰand Ⅱ according to International Federation of Gynecology and Obstetrics (FIGO) stage (P =0.036),in lymph node metastasis group than in none lymph node metastasis group ( P =0.027 ),in stage G3 than in stage G1 and G2 according to Silverberg stage (P =0.003),and in serous adenocarcinoma group than in non-serous adenocarcinoma group (P=0.049);positive rates of ER and Ki-67 were higher than negative rates of ER(P=0.000) and Ki-67 (P =0.009) respectively.Down-regulation of E-cadherin expression was higher in FIGO stage Ⅲ and Ⅳ than in stage Ⅰ and Ⅱ (P =0.044),in serous adenocarcinoma group than in non- serous adenocarcinoma group ( P =0.022) ; positive rates of ER and Ki-67 were higher than negative rates of ER ( P =0.02 1 ) and Ki-67 (P=0.035) respectively.The expression of AIB1 was negatively correlated with E-cadherin expressioh (P =0.026).ConclusionsThe expressions of AIB1 and E-cadherin in OC tissues is closely related to clinical stage.Therefore,AIB1 and E-cadherin may be important moleculars involved in the progression of OC.

Background Clinical work found that triamcinolone acetonide (TA)bleeding during vitrectomy in proliferative diabetic retinopathy (PDR),but its mechanism is not clear.Objective This study was to explore the anastalsis of TA in vitrectomy for PDR.Methods A prospective study was performed.Twelve eyes of 12 patients who received vitrectomy combined with the intraocular use of TA for PDR were in cluded in Tianjin Medical University General Hospital from 2011 to 2014 and served as TA group.Thirty-two eyes of 32 patients who underwent vitrectomy for epimacular membrane or macular hole were enrolled as control group.The vitreous specimens of 0.6 ～0.8 ml was collected during the surgery.The concentrations of urokinase plasminogen activator (u-PA),tissue plasminogen activator (t-PA) and plasminogen activator inhibitors 1 (PAI-1) in vatreous were measured by ELISA.Results The mean contents u-PA,t-PA and PAI-1 in the vatreous were 25.45,127.44 and 0.42 ng/ml respectively in the TA group,and those the mean contents in the control group were 22.94,142.37 and 0.27 ng/ml respectively,shouwing a significant difference between the TA group and the control group (Z=-2.268,P＜0.05).NO significant difference was found in vitreous t-PA and PAI-1 between TA and control groups (Z =-0.092,-1.847,both at P＞0.05).Conclusions Vitreous u-PA content is increased in PDR eyes,which is more likely to lead bleeding.Anastalsis of TA during vitrectomy for PDR may be relatived to decreasing vitreous t-PA and u-PA contents as well as increasing PAI-1 contents.

Objective:To investigate the mechanism of programmed death 1(PD-1)/ programmed death ligand 1(PD-L1) signaling pathway and its feasibility as a potential therapeutic target and prognostic predictor by detecting the expressions, of PD-1 and PD-L1 in bone marrow mononuclear cells of children with acute lymphoblastic leukemia (ALL), and to provide new ideas for the diagnosis and treatment of ALL as well.Methods:Bone marrow samples were collected from 59 children with ALL in the First Affiliated Hospital of Zhengzhou University from September 2018 to July 2019.Flow cytometry was applied to detect the expression of PD-1 and PD-L1 in bone marrow mononuclear cells in 59 ALL patients, including 47 newly-diagnosed ALL patients and 12 relapsed ALL patients, respectively, at initial diagnosis, after induction therapy and early intensive treatment.Their relevant clinical data were collected and compared with the bone marrow specimens of 12 children suffering from non-malignant blood diseases as the control group of the same hospital during the same period.Results:There was no significant difference in the expression of PD-1 in the bone marrow mononuclear cells of the primary diagnosis group, recurrence group and control group ( H=2.402, P>0.05). The expression of PD-L1 in the relapsed and refractory group [(7.32±3.60)%] and the newly diagnosed group [(3.18±2.37)%] was higher than that in the control group [(0.84±0.39)%], and the differences were statistically significant ( H= 28.048, P<0.05). In the initial treatment group, the expression of PD-L1 in the bone marrow mononuclear cells was the strongest expression before treatment ( B=1.293), followed by after induction treatment ( B=0.036) and after early intensive treatment ( B=0.000), suggesting that there was a downward trend as the continued treatment.The expression of PD-L1 was the weakest expression in the low-risk group ( B=-3.912) than in the medium-risk group ( B=-3.595) and high-risk group ( B=0.000), revealing that the expression of PD-L1 is related to the risk grades of ALL.The higher the risk rating is, the higher the PD-L1 protein expression is. Conclusions:The high expression of PD-L1 may be involved in the pathogenesis and be used as an adverse predictor of ALL childhood and an evaluation index of chemotherapy efficacy.PD-1 / PD-L1 signaling pathway may be a potential therapeutic target of ALL childhood.

Objective:To explore the clinical efficacy and safety of Ruxolitinib, a Janus kinase inhibitor, in combination with Methylprednisolone as a bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for relapsed/refractory Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) in pediatric patients.Methods:The clinical data of 4 patients with relapsed/refractory EBV-AHS treated with Ruxolitinib in combination with Methylprednisolone as a bridge to allo-HSCT at the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from August 2018 to February 2020 were retrospectively analyzed, and the disease characteristics, diagnosis and treatment process, clinical experience and related research progress were analyzed and summarized.Results:Among 4 patients with relapsed/refractory EBV-AHS, 2 patients were treated with low-dose Ruxolitinb in combination with Methylprednisolone for 6-10 weeks after partial remission.The disease did not progress, and they survived after being bridged to allo-HSCT.One patient was treated with large-dose Ruxolitinib in combination with Methylprednisolone due to the intolerance to chemotherapy, with the biochemical indicators of hemophagocytic syndrome significantly improved, and then the bridging to allo-HSCT was performed 2 months ago and this patient survived.One patient with EBV-AHS relapsed was relieved by chemotherapy again, then was given maintenance therapy with Ruxolitinib and Methylprednisolone, but the condition still progressed and the treatment was ineffective.This patient underwent allo-HSCT for salvage treatment more than 1 year ago and survived.Except that 1 patient developed mild anemia, the other 3 patients had no significant Ruxolitinib-related toxicities.Conclusions:Ruxolitinib in combination with Methylprednisolone can be safely employed as a salvage treatment for pediatric patients with relapsed/refractory EBV-AHS and a bridge to allo-HSCT, which has favorable safety, efficacy and tolerance in clinical practice.

Objective:To investigate the clinical value of the expression levels of biological protein markers regenerating islet-derived protein 3-alpha(REG3α), soluble tumor suppressor factor 2(sST2) and tumor necrosis factor receptor 1(TNFR1) in peripheral blood in the diagnosis and efficacy evaluation of intestinal acute graft-versus-host disease (aGVHD) in children after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Retrospective analysis of 50 children who underwent allo-HSCT, in the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from January 2020 to February 2021 were enrolled, including 39 males and 11 females [median age: 8.5 (1-13) years]. The expression levels of above 3 biological proteins were detected before transplantation, 1 week, 2 weeks, 3 weeks, 5 weeks, 7 weeks, 9 weeks, 11 weeks and 13 weeks after transplantation, when intestinal aGVHD occured, and after treatment.Children with intestinal aGVHD were taken as the observation group, and children without intestinal aGVHD were taken as the control group.Whether differences in the expression levels of the 3 biological proteins in the peripheral blood of the 2 groups of children were statistically significant was analyzed.The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of the above three biological proteins for intestinal aGVHD, and independent sample t test was performed to compare the expression levels of the 3 biological proteins before and after treatment in children with intestinal aGVHD. Results:(1) The concentrations of REG3α, sST2, and TNFR1 in the peripheral blood of the observation group were (33 985.42±24 631.33) ng/L, (139 899.66±115 825.65) ng/L, (3 041.65±2 418.72) ng/L, respectively, which were higher than the control group of (7 457.39±4 547.49) ng/L, (32 059.57±23 452.85) ng/L, (1 944.51±1 170.35) ng/L, the difference was statistically significant ( t=6.04, 5.19, 2.17, all P<0.05). (2) The area under ROC curve (AUC) of REG3α combined with sST2 in the diagnosis of intestinal aGVHD was 0.952 (95% CI: 0.851-0.992, P<0.001), the maximum Youden index was 0.894, the corresponding sensitivity was 83%, and the specificity was 99%.Its diagnostic value was better than REG3α, sST2 and TNFR1 ( Z=1.763, 1.332, 3.001, all P<0.05). (3) The concentrations of REG3α, sST2, and TNFR1 before treatment in the peripheral blood of children having received effective treatment were (31 343.01±25 364.71) ng/L, (146 629.52±110 501.04) ng/L and (2 489.00±859.70) ng/L, respectively, which were (12 104.37±11 704.60) ng/L, (93 539.55±81 920.93) ng/L and (2 048.15±813.47) ng/L after treatment, lower than those before treatment.The expression levels of REG3α and sST2 were significantly reduced ( t=-3.23, -2.10, all P<0.05), while the difference of the expression level of TNFR1 before and after treatment was not statistically significant ( P>0.05). Conclusions:REG3α and sST2 can be used as important reference indicators for clinical auxiliary diagnosis of intestinal aGVHD, and have good auxiliary diagnostic value.REG3α and sST2 can be used as objective indicators to evaluate the efficacy of clinical treatment of intestinal aGVHD.