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With the wide application of tyrosine kinase inhibitor (TKI), to obtain treatment-free remission (TFR) has gradually become the long-term goal for patients with chronic myelogenous leukemia (CML). Self-renewing leukemia stem cells during disease progression are related with the recurrence, and surveillance of residual leukemic cells is hypothesized to be one of the critical factors in successful TFR. On the way to obtain TFR, many breakthroughs have been made in innate and adaptive immunity of CML cells. This paper reviews the immune function of CML patients, the role of the immune markers in maintaining TFR, and the exploration of TKI combined with new immunomodulator therapy to achieve a greater degree of TFR.
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Objective:To investigate the dynamic expression of histone methyltransferase (enhance of zeste homolog 2, EZH2) in peripheral blood B lymphocytes (CD19 +B) and memory B lymphocytes (CD19 +CD27 +B) of septic patients and its value in predicting prognosis in sepsis. Methods:From June 2018 to January 2020, 48 septic patients in the Intensive Care Unit of Shanghai East Hospital were enrolled, and 40 healthy adult volunteers were recruited as healthy controls. Septic patients were divided into the non-survivors (18 cases) and the survivors (30 cases) according to whether the patients survived at 28 days. Blood samples were collected at day 1, 3 and 7, blood routine, IL-6 and blood gas analysis were collected, and SOFA and APACHE Ⅱ scores were counted. Flow cytometry was used to detect the positive rate and the mean fluorescence intensity of EZH2 on CD19 +B lymphocytes, and the positive rate of EZH2 on CD19 +CD27 +B lymphocytes at different time points. In the healthy controls, fasting was taken only once in the morning. ROC curve was drawn and the area under the curve (AUC) was calculated to evaluate the value of expression of EZH2 on CD19 +B lymphocytes and CD19 +CD27 +B lymphocytes in predicting the prognosis of septic patients. Results:(1) Compared with the healthy controls, the positive rate and average fluorescence intensity of EZH2 on CD19 +B lymphocytes and the positive rate of EZH2 expression on CD19 +CD27 +B lymphocytes were significantly increased at day 1, 2 and 3 in septic patients ( P<0.05). Over time, the expression of EZH2 in CD19 +B lymphocytes and CD19 +CD27 +B lymphocytes increased gradually ( P<0.05). (2) Compared with the survivors, the positive rate of EZH2 on CD19 +B lymphocytes of the non-survivors was increased at day 1, but the positive rate of EZH2 on CD19 +CD27 +B lymphocytes of the non-survivors was decreased at day 3 and 7 ( P<0.05). (3) The positive rate of EZH2 on CD19 +B lymphocytes, APACHE Ⅱ score, SOFA score and IL-6 level in septic patients at day 1 were independently associated with 28-day mortality. (4) The AUC of APACHEⅡ score was 0.907 (95% CI: 0.825-0.990), and the sensitivity and the specificity were 88.89% and 76.67%. The AUC of SOFA score was 0.831 (95% CI: 0.706-0.955), and the sensitivity and the specificity was 66.67% and 86.67%; The AUC of EZH2 positive rate on CD19 +B lymphocytes were 0.799 (95% CI: 0.657-0.941), and the sensitivity and specificity were 88.89% and 80.77%, respectively, the sensitivity was better than SOFA score, and the specificity was higher than APACHEⅡ score. Conclusions:The high expression of EZH2 on B lymphocytes in septic patients is associated with poor prognosis. Dynamic monitoring of EZH2 expression on B lymphocytes has certain predictive value for sepsis.
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Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by heterotopic Ph chromosome. Tyrosine kinase inhibitor (TKI) has significantly improved the prognosis of patients with CML. Cytogenetic and molecular monitoring for assessing the therapeutic efficacy of TKI to guide disease management has become an important component of CML therapy. However, the expanded genomic analysis of the disease diagnosis, transformation and drug resistance has not been fully explored in CML research. The paper reviews the frequency and type of gene mutations at initial diagnosis and the time of treatment failure and transformation, and investigates the relationship between genetic mutations and the prognosis of CML patients in the diagnosis and treatment.
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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.
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Objective To compare the effect of different enteral nutritional support methods in elderly patients with severe pneumonia.Methods Elderly patients (average age over 65 years) with severe pneumonia admitted to our hospital from June 2015 to June 2018 were selected as the study subjects,and 86 patients finally completed the study.The patients were randomly divided into the control group and observation group with 43 patients in each group,and nasojejunal tubes were placed for patients in both groups.Patients in the observation group were fed with enteral nutrition emulsion through continuously-heated nutritional pump,while patients in the control group was meal served with enteral nutrition emulsion.Changes in blood biochemical parameters,immune indexes,inflammation indexes,oxygenation indexes,the GIDF and SOFA scores as well as curative effect (mechanical ventilation time and effective rate of treatment) were monitored and compared before and after 10 days of nutritional support treatment.SPSS 20.0 statistical software package was used for data analysis,and self paired t-test was used for comparison before and after intervention in the same group,x2 test was used in comparison between different groups,and the counting data was expressed as the rate (n,％).Results There was no significant difference in baseline data between patients in the two groups (P＞0.05).After ten days of intervention,compared with the control group,the levels of serum albumin and prealbumin in the observation group were higher [(31.22±2.36) g/L and (0.29±0.24) g/L,P=0.015 and P=0.023],the immune indexes were higher [IgG (13.24±0.70) g/L,P=0.020;IgM (1.43±0.19) g/L,P=0.011;CD4+/CD8+ 1.55±0.49,P=0.043],the inflammation indexes were lower [IL-6 (312.54±42.53) pg/mL,P=0.031;PCT (1.56±0.81) ng/mL,P=0.017],the oxygenation indexes were better [PaO2/FiO2 (315.58±20.37) mmHg,P=0.019],and the GIDF and SOFA scores were significantly lower[(10.6±l.2) and (8.5±1.7),P=0.041 and P=0.038].The clinical outcome showed that the mechanical ventilation time in the observation group was significantly shorter [(6.01±1.48) d vs (8.12 ± 1.17)d,P=0.039],and the total effective rate of treatment was better than the control group (67.44％ vs 41.86％,P=0.027).Conclusions Enteral nutrition support through continuously-heated nutritional pump can improve the nutritional status of elderly patients with severe pneumonia,reduce the incidence of gastrointestinal dysfunction,maintain stable organ fuction,thus resulting in better prognosis in elderly patients with severe pneumonia.
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AIM To investigate the influences of Astragalus and Hurido effective components on apoptosis of rat glomerular mesangial cells.METHODS The proliferation of rat mesangial cells was induced by LPS and then intervened with Astragalus (astragalus polysaccharide,astragaloside Ⅳ,calycosin) and Hurido (hirudin).The cells were collected after 24 h.4',6-Diamidino-2-phenylindole (DAPI) staining was used to observe cell nuclear changes.Quantitative and qualitative expressions of Bcl-2 were detected by streptavidin-biotin complex (SABC).RESULTS Astragalus and Hurido effective components could induce the apoptosis of rat glomerular mesangial cells,and decrease the expression of Bcl-2.CONCLUSION Astragalus and Hurido effective components can induce the mesangial cell apoptosis by down-regulating Bcl-2 expression,which can be used for the treatment of mesangial proliferative glomerulonephritis.
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Objective To explore the time course of response inhibition function in juvenile delin-quents with antisocial personality characteristics.Methods The healthy control group ( n=21),juvenile delinquents with antisocial personality characteristics ( CD +AP ) ( n=18) and juvenile delinquents ( CD) ( n=18) were selected in current study by recording the event-related potentials in a Go/Nogo task.N2 and P3 components of event-related potentials were analyzed.Results Behavioral results showed that Nogo cor-rection rate of control group ((93.13±2.71)%) were significantly higher than CD group ((87.51±2.82)%, P<0.01) and CD +AP group((85.63±2.45)%, P<0.01).In CD+AP group,the amplitude of the N2nogo ( (-1.82±1.64)μV) was significantly lower than control group ( (-6.36±2.93)μV, P<0.01) ,and the am-plitude of the P3nogo ((5.52±2.79)μV) was significantly decreased than healthy control ((11.26±4.92)μV, P<0.01).In CD group,the amplitude of P3nogo ((5.20±3.17)μV) was significantly reduced than healthy control ((11.26±4.92)μV, P<0.01).Conclusion N2nogo and N2d are associated with the early phases of response inhibition and reflected response conflict.P3nogo and P3d are associated with the late phases of response inhibition and monitored inhibitory control.These data suggest that CD+AP participants exhibited im-paired response conflict and inhibitory control.This may be associated with persistent antisocial behavior.