Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review.

Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.

miR-539-5p targets BMP2 to regulate Treg activation in B-cell acute lymphoblastic leukemia through TGF-ß/Smads/MAPK.

MicroRNAs (mRNAs) were believed to play an important role in cancers, and this study aimed to explore the mechanism of miRNA regulating Treg in B-cell acute lymphoblastic leukemia (B-ALL). Firstly, the differentially expressed miRNAs and target genes significantly associated with Tregs were screened out by high-throughput sequencing, and their enrichment pathways were analyzed. The binding relationship between miRNA and target genes was further verified, and the effects of miRNA on the proliferation and apoptosis of B-ALL Nalm-6 cells and Treg activation were analyzed. Results showed that differentially expressed miR-539-5p was significantly under-expressed, and its target gene BMP2 was significantly over-expressed in B-ALL, and significantly enriched in the TGF-ß1 pathway. In addition, both miR-539-5p and BMP2 were significantly correlated with Treg activity in B-ALL. In vitro experiments further confirmed that miR-539-5p could directly target BMP2. The low expression of miR-539-5p in B-ALL significantly promoted BMP2 expression to promote the proliferation and inhibit apoptosis of Nalm-6 cells. Furthermore, the high expression of BMP2 in B-ALL could cooperate with TGF-ß1 to promote the activation of human CD4+CD25-T cells to Treg, and significantly activate the TGF-ß/Smads/MAPK pathway. In vivo experiments also confirmed that overexpression of miR-539-5p significantly inhibited BMP2 to suppress Treg activation and Smad1 and Smad2 phosphorylation, and finally inhibit the B-ALL process. In conclusion, miR-539-5p was significantly under-expressed in B-ALL and could target BMP2 to promote its expression, and the overexpressed BMP2 further promoted Treg activation in B-ALL by regulating TGF-ß/Smads/MAPK pathway.

Confusion in the monitoring of coagulation function in pregnant and neonate patients with severe disease: A case reports and brief literature review.

RATIONALE: Different populations have their own unique physiological and pathological characteristics. However, in specialized maternal and child hospitals, there is currently a lack of standardized methods for assessing coagulation dysfunction, both domestically and internationally. PATIENT CONCERNS: A 19-day-old neonate was transferred to neonatal intensive care unit with cyanosis, nasal bleeding for 6 hours, and a consciousness disorder for 5 hours. A 33-year-old woman presented with hydramnios and a 39 + 3week intrauterine pregnancy. All indicators before delivery were normal, but postpartum hemorrhage occurred after delivery. DIAGNOSES: We retrospectively analyzed 1 neonate with pulmonary hemorrhage accompanied by thrombocytopenia and 1 pregnant patient with amniotic fluid embolism. INTERVENTIONS: The new coagulation indicators, such as thrombin-antithrombin complex, plasmin-alpha 2 antiplasmin complex, thrombomodulin, and tissue plasminogen activator-plasminogen activator inhibitor-1 complex, have been indicated to be valuable. In neonates, it is necessary to continuously monitor special items combined with specific therapeutic agents, such as tranexamic acid. In cases where postpartum hemorrhage occurs with low fibrinogen levels, it is essential to effectively identify patients with severe amniotic fluid embolism from a high incidence of specimen clotting. OUTCOMES: The neonate's oxygen saturation stabilized, and after 5 days of treatment with low molecular weight heparin, thrombin-antithrombin complex and plasmin-alpha 2 antiplasmin complex returned to normal levels. The pregnant began to remove the remaining thrombus, the patient's condition recovered, and she had a good prognosis. LESSONS: For pregnant and neonatal critical illnesses, it is necessary to develop personalized coagulation monitoring programs that provide realistic and reasonable treatment recommendations. Such programs should consider the unique physiological and pathological characteristics of different populations to ensure effective management of critically ill patients.

Effects of Hemolysis on Routine Coagulation Tests when Tested on an Optical Coagulation Analyzer.

BACKGROUND: The Clinical and Laboratory Standards Institute recommends rejecting hemolyzed samples for coagulation tests. Sysmex CS5100 analyzer using an optical method is commonly used in laboratories. The influence of hemolysis on coagulation test has rarely been studied when tested on Sysmex CS5100. Determining this influence is necessary. METHODS: Freshly collected samples were artificially hemolyzed to simulate the hemolysis processes. Coagulation tests were conducted on a Sysmex CS5100 coagulation analyzer. Detection values before and after hemolysis were compared. RESULTS: The results showed that after hemolysis detection, the prothrombin time (PT) statistically decreased, while the partial thromboplastin time (APTT) statistically increased. There were no significant differences in fibrinogen (Fg), thrombin time (TT), D-dimer (DD) or fibrinogen degradation products (FDPs). Antithrombin activity was elevated in hemolyzed samples. CONCLUSIONS: Although differences in PT and APTT were statistically significant, there was no need for rejection of hemolyzed samples due to insufficient clinical effects when tested on Sysmex CS5100 analyzer. Falsely elevated AT result may lead to misdiagnosis in patients with severe diseases, which should be carefully considered.

The possibility of automatic capillary blood testing in routine blood tests: an evaluation of the automatic mode of the Mindray BC-7500 CRP Auto Hematology Analyzer for capillary blood testing.

Background: Capillary blood is a common specimen type used for infant blood routine tests. Until now, this specimen type could only be tested with the manual mode in hematology analyzers. Manual sample mixing and loading increases the amount labor force and can be more easily affected by human factors. This study was designed to investigate the proficiency of the automatic mode of the Mindray BC-7500 CRP Auto Hematology Analyzer for capillary blood testing. Methods: The complete blood count (CBC) results for capillary blood were compared between the automatic and manual modes. Special types of samples, including samples with high or low volume, thalassemia red cells, high fibrinogen, high hematocrit (HCT), or high triglyceride levels, were compared and evaluated. The intraclass correlation coefficient (ICC) was used to define the agreement between the 2 modes. The industry standard Analytical Quality Specifications for Routine Tests in Clinical Hematology (WS/T 406-2012), published by the National Health Commission of China, was used to evaluate the correlation between the results from the 2 modes. Results: There was good correlation between the automatic and manual modes for every type of sample, and the ICCs were all higher than 0.9. Except for high HCT or high triglyceride samples, there were no differences found between the 2 modes based on the WS/T 406-2012 standard. Conclusions: This new automatic mode utilized in the Mindray BC-7500 CRP Auto Hematology Analyzer for capillary blood yielded the same results as the manual mode except in the case of samples with high HCT or triglycerides. Capillary blood might be routinely tested automatically with hematology analyzers in the near future, which might reduce the labor required and improve standardization.

Cytokine network imbalance in children with B-cell acute lymphoblastic leukemia at diagnosis.

Immune imbalance has been proved to be involved in the pathogenesis of hematologic neoplasm. However, little research has been reported altered cytokine network in childhood B-cell acute lymphoblastic leukemia (B-ALL) at diagnosis. Our study aimed to evaluate the cytokine network in peripheral blood of newly diagnosed pediatric patients with B-ALL. Serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon (IFN)-γ, and IL-17A in 45 children with B-ALL and 37 healthy control children were measured by cytometric bead array, while the level of transforming growth factor-ß1 (TGF-ß1) in the serum was measured by enzyme-linked immunosorbent assay. Patients showed a significant increase in IL-6 (p < 0.001), IL-10 (p < 0.001), IFN-γ (p = 0.023) and a significant reduction in TGF-ß1 (p = 0.001). The levels of IL-2, IL-4, TNF and IL-17A were similar in the two groups. Higher concentrations of pro-inflammatory cytokines were associated with febrile in patients without apparent infection by using unsupervised machine learning algorithms. In conclusion, our results indicated a critical role for aberrant cytokine expression profiles in the progression of childhood B-ALL. Distinct cytokine subgroups with different clinical features and immune response have been identified in patients with B-ALL at the time of diagnosis.

Establishment of Review Criteria Coordinating With the Automated Digital Cell Morphology Identification System in a Specialized Women's and Children's Hospital.

OBJECTIVE: We aimed to establish appropriate review criteria for blood cell analysis in a specialized women's and children's hospital. Also, the CellaVision DI-60, was developed as one of the automated digital cell morphology analyzer, we evaluated if it was shown to be most effective under the certain review criteria. METHODS: A total of 2890 blood samples were detected to optimize the previously established review criteria for women and children with the Sysmex XE-2100. A total of 623 samples were used to validate the criteria. RESULTS: The microscopic-review rate based on the initial review criteria was 51.0%. After optimization, it was reduced to 17.3% and the false-negative rate was 3.85%. There was > 80% consistency between manual review results and CellaVision DI-60 preclassification when samples triggered the platelet- or red cell-related rules. The sensitivity for abnormalities (immature granulocytes, nucleated red blood cells) of reclassification was 90% to 100% and the false-negative rate was < 5%. However, direct microscopic review was required when the "Blasts/AbnLympho?" and "Atypical Lympho?" flags were triggered. CONCLUSION: Specialized review criteria are needed for women and children. An automated morphology identification system might help to improve the review criteria.

Coordination of LMO7 with FAK Signaling Sustains Epithelial Integrity in Renal Epithelia Exposed to Osmotic Pressure.

The kidney epithelial barrier has multifaceted functions in body fluids, electrolyte homeostasis, and urine production. The renal epithelial barrier (REB) frequently faces and challenges osmotic dynamics, which gives rise to osmotic pressure (a physical force). Osmotic pressure overloading can crack epithelial integrity and damage the REB. The endurance of REB to osmotic pressure forces remains obscure. LMO7 (LIM domain only 7) is a protein associated with the cell-cell junctional complex and cortical F-actin. Its upregulation was observed in cells cultured under hypertonic conditions. LMO7 is predominantly distributed in renal tubule epithelial cells. Hypertonic stimulation leads to LMO7 and F-actin assembly in the cortical stress fibers of renal epithelial cells. Hypertonic-isotonic alternation, as a pressure force pushing the plasma membrane inward/outward, was set as osmotic disturbance and was applied to test FAK signaling and LMO7 functioning in maintaining junctional integrity. LMO7 depletion in cells resulted in junctional integrity loss in the epithelial sheet-cultured hypertonic medium or hypertonic-isotonic alternation. Conversely, FAK inhibition by PF-573228 led to failure in robust cortical F-actin assembly and LMO7 association with cortical F-actin in epithelial cells responding to hypertonic stress. Epithelial integrity against osmotic stress and LMO7 and FAK signaling are involved in assembling robust cortical F-actin and maintaining junctional integrity. LMO7 elaborately manages FAK activation in renal epithelial cells, which was demonstrated excessive FAK activation present in LMO7 depleted NRK-52E cells and epithelial integrity loss when cells with LMO7 depletion were exposed to a hypertonic environment. Our data suggests that LMO7 regulates FAK activation and is responsible for maintaining REB under osmotic disturbance.

[Prognostic Value of Average Daily Platelet Increase in Childhood B-cell Acute Lymphoblastic Leukemia Patients].

OBJECTIVE: To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen. METHODS: 106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children. RESULTS: The trend of negative correlation existed between PPC and TPR (rs=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×109/L group was 95.7%, which was significantly higher than those in Ap≤5.4×109/L group(79.5%) (χ2=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×109/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×109/L as candidate variables, Ap≤5.4×109/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×109/L (χ2=4.318, P=0.038) could explain the phenomenon. CONCLUSION: Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.

[Prognostic Value of Average Daily Platelet Increase in Childhood B-cell Acute Lymphoblastic Leukemia Patients].

OBJECTIVE: To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen. METHODS: 106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children. RESULTS: The trend of negative correlation existed between PPC and TPR (rs=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×109/L group was 95.7%, which was significantly higher than those in Ap≤5.4×109/L group(79.5%) (χ2=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×109/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×109/L as candidate variables, Ap≤5.4×109/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×109/L (χ2=4.318, P=0.038) could explain the phenomenon. CONCLUSION: Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.

Numerical Study of Contact Behavior and Temperature Characterization in Ultrasonic Welding of CF/PA66.

Ultrasonic plastic welding (UPW) is a promising method for joining carbon fiber reinforced thermoplastic (CFRTP). The interface temperature determines weld quality to a large extent. This paper numerically analyzes the contact behavior and temperature characterization during welding using harmonic balance method (HBM). The simulation and experimental results show that amplitude and welding time are important factors determining the interface temperature. Increasing amplitude and welding time can significantly increase the interface temperature. Plunging speed and trigger force have little effect on the interface temperature. For nonlinear contact and heat generation, the results show that there is a certain separation between workpieces and the heat source is mainly friction heat generation in the early stage of welding. With the progress of welding, there is no separation between the workpieces and viscoelastic heat generation begins to dominate.

Prognostic Relevance of Structural Maintenance of Chromosomes 4 Overexpression in Pediatric Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Abnormal expression of structural maintenance of chromosomes (SMC) 4 has been observed in multiple tumors and plays a vital role in cancer development. However, the association between SMC4 expression and clinical characteristics in Chinese childhood patients with ALL is unknown. Thus, this study aimed to investigate the relationship between SMC4 expression and clinical features and prognosis in these patients. METHODS: Real-time quantitative polymerase chain reaction (PCR) was performed to detect the expression of SMC4 in Chinese pediatric ALL patients and in patients achieving complete remission (CR). Then, the relationships between SMC4 expression and clinical features, such as gender, age, white blood cell (WBC) count, French-American-British (FAB) classification, immunophenotype, fusion gene, prednisone response, and minimal residual disease (MRD) were determined. Furthermore, survival and prognostic factor analyses were carried out to examine the prognostic value of SMC4 expression. RESULTS: The expression level of SMC4 was significantly higher in bone morrow cells of newly diagnosed pediatric ALL patients than in those of healthy controls (p = 0.006), especially in B-cell precursor ALL (BCP ALL). Moreover, SMC4 expression was correlated with different clinical parameters. Furthermore, a decrease of SMC4 expression was detected in BCP ALL patients achieving CR. The high SMC4 expression group had both worse event-free survival rate and poorer overall survival rate. However, multivariate analysis showed that SMC4 expression was not an independently predictive factor of BCP ALL outcome. CONCLUSIONS: These results revealed that SMC4 expression in BM was associated with various clinical outcomes in pediatric patients with ALL, although it was not an independent outcome factor.

Longer Time Intervals From Symptom Onset to Diagnosis Affect the Overall Survival in Children With Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Early diagnosis and timely treatment are essential for effective cancer control and have been widely analyzed in childhood cancer. However, few studies have described the time to diagnosis and treatment in children with ALL. This study investigated delays in diagnosis and treatment initiation and their impact on survival. METHODS: This retrospective cohort study included 419 patients 0 to 14 years old at a tertiary hospital between 2011 and 2015. The optimal cutoff values for delays were determined by X-tile software. The Kaplan-Meier method and Cox regression models were used to evaluate the impact of delays on survival. RESULTS: The median diagnosis, treatment, and total delays were 21 (interquartile range [IQR]: 11-35), 4 (IQR: 2-7), and 26 (IQR: 16-43) days, respectively. The results of multivariate analyses showed that diagnosis delay, risk stratification, and minimal residual disease level were independent predictors for treatment outcome in childhood ALL. CONCLUSIONS: These findings suggested that a longer time to diagnosis negatively affected the clinical outcome of childhood ALL. Reducing the time to diagnosis could help to improve survival in these patients.

How to Achieve Standardization? Diluted Russell Viper Venom Test for Lupus Anticoagulant Detection in a Chinese Female Population.

On an international scale, guidelines and proposals for lupus anticoagulant detection have been published over the last 20 years, but until now, standardization has not been completely realized. The aim of this study was to evaluate the different ways of interpreting the results of lupus anticoagulant detection for standardization. A retrospective review of 15 447 instances of lupus anticoagulant detection by the diluted Russell Viper Venom test for female patients presenting with problems relating to the areas of reproduction, gynecology and obstetrics was performed. Lupus anticoagulant data were compared between different departments, months, reagent lots and cutoffs. Significant differences were found in patient data between different reagent lots, especially between lots of screening reagents (monthly average: highest 37.96 s vs lowest 33.88 s) and in the positive rates of lupus anticoagulant by different detection cutoffs (47.58% by using LA1/LA2 > 1.20 without normalization as a cutoff in Lot 1 vs 1.52% by using LA1 > 44 s as a cutoff in Lot 3). Compared with the cutoff using the value above the 99th percentile of LA1 for the healthy donors per lot, the cutoff using integrated tests with normalization had the smaller deviation of positive rate between different reagent lots. Pregnant women had higher LA1/LA2 levels than nonpregnant women. Based on the results, normalization is needed because there are significant lot-to-lot variations. Integrated tests with normalization might be a better standard by which to confirm lupus anticoagulant. Pregnant women should have population-specific cutoffs because they have higher LA1/LA2 levels.

Effect of Cyclical Microwave Modification on the Apparent Permeability of Anthracite: A Case Study of Methane Extraction in Sihe Mine, China.

The application of cyclical microwave modification for accelerating the extraction of coalbed methane (CBM) from anthracite is limited. In this study, the apparent permeability of anthracite samples before and after each microwave treatment (three in total) for 120 s was measured by a self-built permeability-testing platform. Microcomputed tomography (micro-CT) technology and image-processing technology were employed to analyze the 3D micron-scale pore structures, especially the quantitative characterization of connected pores and throats. After modification, the average apparent permeability increased from 0.6 to 5.8 × 10-3 µm2. The generation, expansion, and connection of micron-scale pores and fractures became more obvious with each treatment. The total porosity increased from 3.5 to 6.2%, the connected porosity increased from 0.9 to 4.8%, and the porosity of isolated pores decreased from 2.5 to 1.4% after three cycles. The number, volume, and surface area of the connected pores as well as the number, radius, and surface area of the throats were significantly increased. In addition, the release of alkyl side chains from the anthracite surface reduced the capacity of the anthracite to adsorb CH4 and the decomposition of minerals promoted the development and connectivity of pores. As a result, the gas seepage channels have been greatly improved. This work provides a basis for micron-scale pore characterization after cyclical microwave modification and contributes to CBM extraction.

Combined use of peripheral blood blast count and platelet count during and after induction therapy to predict prognosis in children with acute lymphoblastic leukemia.

ABSTRACT: Several studies have reported an association between the rapidity of reduction in peripheral blood blast count or recovery of normal hematopoiesis and treatment outcome during therapy in children with acute lymphoblastic leukemia (ALL). However, little is known about the impact of both of these aspects on prognosis in pediatric ALL. Accordingly, the purpose of this study was to evaluate whether the combined use of blood blast count and platelet count could predict event-free survival (EFS) and overall survival (OS) when minimal residual disease (MRD) detection was not available.A total of 419 patients aged 0 to 14 years diagnosed and treated for ALL between 2011 and 2015 were enrolled.Patients with a blast count ≥0.1 × 109/L on day 8 exhibited significantly lower survival rates than that in those with blast counts <0.1 × 109/L. The EFS and OS in patients with platelet count ≥100 × 109/L on day 33 were significantly higher than those with platelet counts <100 × 109/L. In univariate and multivariate analyses, patients with low blast count on day 8 and high platelet count on day 33 were significantly associated with better EFS and OS. The combination of blast cell count on day 8 and platelet count on day 33 demonstrated a strong association with MRD-based risk stratification.Complete blood count is an inexpensive, easy to perform, and reliable measurement in children with ALL. The combination of blast count and platelet count during and after induction chemotherapy was a significant and independent prognostic factor for treatment outcome in pediatric ALL.

Clinical features and outcome of pediatric acute lymphoblastic leukemia with low peripheral blood blast cell count at diagnosis.

ABSTRACT: Peripheral blood (PB) blast cell count on day 8 of prednisone therapy has been considered one of the strongest predictors of outcome in children with acute lymphoblastic leukemia (ALL). However, little is known about the clinical features and prognostic impact of PB blast cell count at diagnosis in these patients. The aim of this study was to evaluate the relationship between initial PB blast cell count and clinical prognosis of pediatric ALL.The study comprised 367 patients with ALL, aged 0 to 14 years, enrolled and treated using the Chinese Children's Leukemia Group-ALL 2008 protocol between 2011 and 2015. The majority (91.6%) of patients were B-cell precursor ALL (BCP ALL), and 8.4% were T-cell ALL (T-ALL).Patients with BCP ALL in the low PB blast cell count group (<1 × 109/L) had significantly superior survival rates to those in the high count group (≥30 × 109/L). In T-ALL, the low count group showed significantly inferior survival rates compared to both the intermediate count group (1-29.9 × 109/L) and high count group. Multivariate analysis revealed that the initial white blood cell count and minimal residual disease at the end of induction therapy were independently predictive of BCP ALL outcome, while risk stratification was shown to be an independent prognostic factor for T-ALL outcome.These results indicated that low blast cell count in PB at diagnosis was associated with different clinical outcomes in patients with BCP ALL and T-ALL, although it was not an independent outcome predictor by multivariate analysis.

Targeting Thyroid Receptor Interacting Protein 6 by MicroRNA-589-5p Inhibits Cell Proliferation, Migration, and Invasion in Endometrial Carcinoma.

Background: MicroRNA-589-5p (miR-589-5p) has been recently reported to be aberrantly regulated in hepatocellular carcinoma, but its functional role and molecular mechanisms still remains unknown in the endometrial carcinoma (EC) as one of the most common female malignancies. Methods: EC tissues and adjacent tissues were collected to determine the expression of miR-589-5p and thyroid receptor interacting protein 6 (TRIP6) using quantitative real time-PCR. Subsequently, two EC cell lines HEC-1B and AN3CA were transfected with miR-589-5p to achieve miR-589-5p overexpression. Using Cell Counting Kit-8 (CCK-8), a wound healing assay and the Transwell assay, we analyzed cell proliferation, migration and invasion. Dual-luciferase reporter assay confirmed that thyroid receptor interacting protein 6 (TRIP6) was a direct target of miR-589-5p. Results: We first observed that miR-589-5p was down-regulated in EC tissues compared with normal endometrial tissues. MiR-589-5p overexpression significantly suppressed EC cell proliferation, migration and invasion. Thyroid receptor interacting protein 6 (TRIP6) was a direct target of miR-589-5p. Besides, TRIP6 knockdown presented similar effects on cell proliferation, migration and invasion to miR-589-5p overexpression. Furthermore, TRIP6 knockdown efficiently enhanced the effects of miR-589-5p on the above cellular function. Moreover, miR-589-5p up-regulated E-cadherin expression, but down-regulated N-cadherin and Vimentin by targeting TRIP6. Conclusions: In summary, miR-589-5p might function as a tumor suppressor by targeting TRIP6, which will provide new insights into the molecular mechanism underlying the development of EC.

Clinical value of the quantitation of average daily platelet increase during the recovery period in childhood acute lymphoblastic leukaemia.

The time to platelet recovery (TPR) is becoming a predicting factor during the treatment of childhood acute leukaemia. However, the initial pre-treatment platelet count (PPC) could interfere with TPR. Here, we integrated both TPR and PPC as the average daily platelet amount increase (Ap) to predict the prognosis in childhood B-ALL during the recovery period.148 patients were enrolled. The relationship between the Ap and MRD was evaluated, and Multivariate analysis was performed to evaluate whether Ap was independently associated with a better EFS. The PPC was inversely correlated with TPR (rs = -0.519, P = 0.021). Patients in Ap >3.9 × 109/L group had better EFS (x2 = 3.109, P = 0.028) than TPR ≤ 16d. Multivariate analysis indicated that Ap > 3.9 × 109/L was independently associated with a longer EFS (RR = 3.468; 95%CI: 1.037-11.597, P = 0.043). However, when introducing both MRD and Ap > 3.9 × 109/L as candidate variables, the Ap > 3.9 × 109/L lost its independent effect (P = 0.081). The strong association between MRD on treatment day 33 and Ap > 3.9 × 109/L (x2 = 148.00, P = 0.000) was responsible for this phenomenon. Ap could be a valuable prognostic indicator in childhood B-ALL.

[Relationship between Immune Differentiation Antigen and Minimal Residual Disease in Childhood B-ALL].

OBJECTIVE: To determine whether immune differentiation antigen is related with clinical features and minimal residual disease (MRD) in childhood B-cell precursor acute lymphoblastic leukemia (B-ALL), who were treated with CCCG-ALL-2015 protocol. METHODS: A retrospective analysis was conducted in 132 B-ALL children, Multiparametric flow cytometry was used to analyze the immunophenotypes. The children were divided into 2 groups by MRD>0.1% on d 19 and / or d 46 after chemotherapy. The Wilcoxon rank-sum test and χ2 test were used for the comparison between groups, and P<0.05 was considered statistically significant. RESULTS: CD19 (100%), CD22 (99.3%) and cCD79a (97.9%) were specific markers for patients with B-ALL, the CD13 and CD33 were mainly cross myeloid antigen. The significant differences were found between CD45- and CD45+ in WBC counts when being firstly diagnosed (Z=6.845, P<0.01), risk stratification (χ2=8.260, P<0.05) and prednisone poor responder (χ2=18.420, P<0.01). Significant differences were found between CD10- and CD10+ in age (Z=6.253, P<0.05), risk stratification (χ2=6.699, P<0.05) and MRD (χ2=4.951, P<0.05). CONCLUSION: In CCCG-ALL-2015 protocol, the CD10 relates with the early MRD, suggesting a better prognosis, and reducing the adverse effects of CD20 and cross myeloid antigen on prognosis.