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Objective:To investigate the effect of rapamycin (Rapa) on apoptosis of acute myeloid leukemia THP-1 cells induced by idarubicin (IDA) and its molecular mechanism.Methods:The THP-1 cells were treated with 10, 20, 40 and 80 nmol/L Rapa for 1 h, and the cells without Rapa treatment were set up. Western blot was used to detect the conversion of autophagy marker LC3 protein in THP-1 cells (the ratio of LC3Ⅱ/LC3Ⅰ), flow cytometry was used to detect the apoptotic rate, and the pretreatment concentration of Rapa was determined. THP-1 cells were treated with different concentrations of IDA for 24 h, the cell proliferation inhibition rate of IDA for THP-1 cells was detected by CCK-8 method, and the half maximal inhibitory concentration ( IC50) was calculated. THP-1 cells with or without Rapa treatment were treated by IDA with the concentration of lower than IC50 for 24 h, CCK-8 method was used to detect cell proliferation inhibition rate, flow cytometry was used to detect cell apoptosis, real-time fluorescent quantitative polymerase chain reaction was used to detect the expression changes of autophagy-related genes Beclin-1, LC3 and p62, and Western blot was used to detect the conversion of autophagy marker LC3 protein. Results:The ratio of LC3Ⅱ/LC3Ⅰ in THP-1 cells treated by 20 nmol/L Rapa was higher than that in the untreated cells ( P=0.002 4). The apoptotic rate in THP-1 cells treated by 80 nmol/L Rapa was higher than that in the untreated cells ( P=0.007 3). According to the results of Western blot and flow cytometry, 20 nmol/L Rapa was selected as the pretreatment concentration. The IC50 of IDA for THP-1 cells treated with IDA for 24 h was 59.874 nmol/L. After treated with 50 nmol/L IDA for 24 h, the proliferation inhibitory [(69.67±5.03)% vs. (41.67±3.51)%] and apoptotic rates [(74.35±4.83)% vs. (41.25±5.24)%] in THP-1 cells pretreated by Rapa were higher than those in the unpretreated cells (both P<0.05); the Beclin-1 and LC3 mRNA expression levels and the ratio of LC3Ⅱ/LC3Ⅰ in THP-1 cells pretreated by Rapa were higher than those in the unpretreated cells, and the expression of p62 mRNA was lower than that in the unpretreated cells (all P<0.05). Conclusion:Rapa can enhance the apoptosis of THP-1 cells induced by a relative low dose of IDA, which may be achieved through inducing excessive autophagy in THP-1 cells.
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Objective:To explore the expression of Fbxw7 protein and its clinical significance in diffuse large B-cell lymphoma (DLBCL), and to provide a basis for prognostic judgement and searching the new therapeutic targets of DLBCL.Methods:A total of 72 patients with newly diagnosed DLBCL who received immunohistochemical detection of c-myc protein from January 2011 to September 2017 in Cancer Hospital Affilicoted to Zhengzhou University were enrolled. The paraffin-embedded specimens after lymph node biopsy and the clinical data of patients were also collected. At the same time, 22 samples of lymph node reactive hyperplasia were selected as the control group. Immunohistochemical method was used to detect the expression of Fbxw7 protein in DLBCL tissues and control tissues. The relationship between the expression of Fbxw7 protein and c-myc protein, the association of Fbxw7 protein expression with DLBCL patients' clinicopathological characteristics, efficacy and prognosis were analyzed.Results:The positive rate of Fbxw7 protein in DLBCL tissues was lower than that in control tissues, and the difference was statistically significant [63.89% (46/72) vs. 86.36% (19/22), χ 2 = 3.990, P = 0.046]. Among DLBCL patients, the positive rate of Fbxw7 protein in non-germinal center B cell (non-GCB) group was lower than that in germinal center B cell (GCB) group, and the difference was statistically significant [48.15% (13/27) vs. 73.33% (33/45), χ 2 = 4.639, P = 0.031]. There were no statistically significant differences in the positive rate of Fbxw7 protein among patients with different age, gender, neoplasm staging, international prognostic index (IPI) scores, B symptom, Eastern Cooperative Oncology Group (ECOG) score, lactate dehydrogenase (LDH) level, β 2 microglobulin level, and therapeutic efficacy after initial treatment (all P > 0.05). In DLBCL tissues, the expression of Fbxw7 and c-myc protein was negatively correlated ( r = -0.255, P = 0.031). The 3-year overall survival (OS) rate and 3-year progression-free survival (PFS) rate (88.3% and 82.0%) of the Fbxw7 positive group were higher than those of the Fbxw7 negative group (70.2% and 60.1%). Cox multivariate analysis showed that the down-regulation of Fbxw7 protein expression was an independent risk factor affecting OS and PFS in DLBCL patients ( HR = 3.656, 95% CI 1.055-12.674, P = 0.041; HR = 2.897, 95% CI 1.092-7.688, P = 0.033). Conclusions:The expression of Fbxw7 protein and c-myc protein in DLBCL patients is negatively correlated. Fbxw7 protein is down-regulated in DLBCL, and it is more obvious in non-GCB subtype. The down-regulated expression of Fbxw7 protein is related to the poor prognosis of DLBCL, and Fbxw7 may become a new therapeutic target of DLBCL.
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Objective To analyze the risk factors of early acute kidney injury (AKI) after liver transplantation from donation after cardiac death(DCD) donor liver. Methods Clinical data of 184 donors and recipients undergoing liver transplantation from DCD donor liver were retrospectively analyzed. According to the incidence of early AKI, all participants were divided into the AKI and non-AKI groups. The patients in the AKI group were subject to AKI staging. Baseline data, preoperative, intraoperative and postoperative related parameters were statistically compared between two groups. The cumulative survival rate and clinical prognosis of patients in non-AKI group and AKI group with different staging were statistically analyzed by Kaplan-Meier curve analysis. Results Among 184 patients, 68 cases (37.0%) presented with early AKI after liver transplantation including 31 stage 1 AKI, 26 stage 2 AKI and 11 stage 3 AKI, mainly occurring within postoperative 3 d. Univariate analysis revealed that preoperative levels of albumin <35 g/L, preoperative levels of serum sodium ≤137 mmol/L, operation time>7.5 h, intraoperative hemorrhage volume>3 000 mL, intraoperative red cell infusion volume>15 U and intraoperative urine amount ≤100 mL/h were the risk factors of early AKI after liver transplantation (all P<0.05). Multi-variate Logistic regression analysis demonstrated that intraoperative red cell infusion >15 U was an independent risk factor of early AKI after liver transplantation [odds ratio(OR) 1.061, 95% confidence interval(CI)1.008-1.118,P=0.024].Result of Kaplan-Meier survival curve suggested that the cumulative survival rate was gradually reduced along with the aggravation of AKI with statistical significance (all P<0.05). Conclusions The incidence of early AKI following liver transplantation is relatively high. The severity of early AKI is intimately correlated with the short- and long-term prognosis of the recipients. A large quantity of intraoperative red blood cell infusion is an independent risk factor of AKI.
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Objective@#To explore the clinical and laboratory features of chronic myeloid leukemia(CML) patients with blast phase as initial presentation.@*Methods@#The clinical manifestation, laboratory bindings and treatment of 3 CML patients with blast phase as the initial presentation from January 2015 to November 2016 in Luoyang Central Hospital Affiliated to Zhengzhou University were analyzed. The first symptoms of 3 patients were similar to acute leukemia.@*Results@#The patients were presented with splenomegaly, obvious rise of white blood cell count in peripheral blood, increasing number of initial cells in the bone marrow, Philadelphia chromosome-positive (Ph+), fluorescence in situ hybridization of bcr-abl1 with fusion signals in segmented granulocytes, fusion gene with p210 positive and without the typical chronic phase of CML.@*Conclusions@#Due to the increased number of marrow blasts and the similarity of clinical manifestations to acute leukemia in CML patients with blast phase as the initial presentation, it is easy to misdiagnose as Ph+ acute leukemia in the initial phase. While some differences in genetics, clinical manifestations and genomics between them may help in differential diagnosis.
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Objective To analyze the clinicopathological characteristics and the prognostic survival factors of young patients who have undergone hepatectomy for primary hepatic carcinoma.Methods Clinicopathological da-ta and treatment outcomes in 79 young (≤40 years old)and 67 elderly (≥65 years old)patients who underwent hep-atectomy for primary hepatic carcinoma between 2008 and 2012 were retrospectively collected and compared using various parameters.Then the survival rate and prognostic factors of the younger patients were analyzed using Kap-lan-Meier and COX multivariate proportional hazards model.Results The positive rate of HBs-antigen and alpha-fetoprotein level were significantly higher in the younger patients than in the elderly patients (P0.05).The overall survival rate was similar between the two groups.COX multivariate proportional hazards model analysis showed that the independent prognostic factors of overall survival were pre-operative albumin level <3 5 g/L and maximum tumor diameter ≥5 cm.Conclusion Hepatectomy is a safe and feasible treatment for young and elderly patients with primary hepatic carcinoma.The independent prognostic factors of survival for young patients are pre-operative albumin level <3 5 g/L and the maximum tumor diameter ≥5 cm.
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Objective To determine the perioperative risks of partial hepatectomy by determining the preoperative liver functional reserve in patients with hepatocellular carcinoma (HCC),and to compare the model for end-stage liver disease (MELD) score with the Child-Pugh classification in predicting prognosis.Methods We reviewed the clinical data of 202 patients with HCC who underwent partial hepatectomy.The MELD score and the Child-Pugh classification were determined preoperatively.Results The incidence of postoperative liver dysfunction happened in 44.0％ of Child A patients,50％ in Child B patients,41.6％in patients with a MELD score below 14,and 91.7％ in patients with a MELD score of ＞ 14.The difference between the rates of postoperative liver dysfunction in patients with a preoperative MELD score above 14 and below 14 was significant (P ＜ 0.05),while that between patients with Child-Pugh A and B was insignificant (P ＞ 0.05).The incidences of postoperative liver dysfunction in patient with a MELD ＜ 8,8 ≤ MELD ≤ 14,MELD ＞ 14 were 38.2％,57.6％ and 91.7％,respectively,indicating that there was a positive co-relationship between the MELD score and the incidences of liver dysfunction.The Spearman rank correlation test showed the MELD score was significant correlated with the Child-Pugh score (r =0.404 ; P ＜ 0.05).The areas under the ROC curves of the MELD score and the Child-Pugh score were 0.703 and 0.587 (P ＜ 0.05).Conclusions The MELD score predicted postoperative liver dysfunction more accurately than the Child-Pugh classification.HCC patients undergoing partial hepatectomy with a preoperative MELD score ＞ 14 had a high perioperative risk.To ensure the safety of partial hepatectomy,HCC patients with a preoperative MELD score ＞ 14 requires active preoperative preparation,bringing the score near to or less than 14.
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Objective To study the significance of the expression of β-catenin(β-cat) in Barrett esophagus and esophageal adenocarcinoma (EAC) and the relationship between its expression and clinicopathological factom.Methods By using SP immunohistochemistry technique,β-cat wag detected in the normal esophageal mucosa group (20 cases),Barrett esophagus with dysplasia group (26 cages) and EAC group (50 cases).Results The membranous expression of β-cat appeared in all of nomal esophageal mucosa.The rate of cytoplasmic and/or nuclear expression of β-cat in the Barrett esophagus with dysplasia group and the EAC group was 38.5% (10/26) and 60.0% (30/50) respectively,and compared with the normal esophageal mucosa group,the difference was signfficant (P＜0.01).The rate of cytoplasmic and/or nuclear expression of β-cat in the EAC group with lymphatic metastasis and the EAC group exceeding deep smooth muscle was 90.0% (18/20) and 72.2%(26/36) respectively,and compared with that in the nonlymphatic metastasis and the non-exceeding deep smooth muscle patients [43-3%(13/30) and 28.6% (4/14)],the difference was significant (P＜0.01).Conclusion Cytoplasmic and/or nuclear expression of β-cat might play a role in the carcinogenesis and progression of EAC and might be a predictor indicating the metastatic potential of EAC.