[Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the expression of Exosome Component 4（EXOSC4） in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance. METHODS: The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance. RESULTS: The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05). CONCLUSION: High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.

Recombinant human thrombopoietin therapy for primary immune thrombocytopenia in pregnancy: a retrospective comparative cohort study.

BACKGROUND: Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients. AIMS: To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response. METHODS: From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count < 30 × 109/L who did not respond to steroids and/or intravenous immunoglobulin were retrospectively analysed. Of these patients, 33 received rhTPO treatment (rhTPO group) while 48 did not (control group). Baseline characteristics, haematological disease outcomes before delivery, obstetric outcomes, and adverse events were compared between groups. In the rhTPO group, a generalised estimating equation (GEE) was used to investigate the factors influencing the response to rhTPO treatment. RESULTS: The baseline characteristics were comparable between both groups (P > 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5-67.5] vs. 25 [19-29] × 109/L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P < 0.001). Gestational weeks of delivery (37.6 [37-38.4] vs 37.1 [37-37.2] weeks, P = 0.001) were longer in the rhTPO group than in the control group. The rates of caesarean section, postpartum haemorrhage, foetal or neonatal complications, and complication types in both groups were similar (all P > 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment. CONCLUSION: rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.

Anterior Talofibular Ligament All-Inside Arthroscopic Reconstruction with InternalBrace™ for Chronic Lateral Ankle Instability.

BACKGROUND Anterior talofibular ligament (ATFL) is the most easily injured or even broken of ankle sprain. Patients who fail to receive conservative treatment, resulting in persistent ankle swelling, painful and functional decline that it is so-called chronic lateral ankle instability (CLAI). It makes sense to investigate all-inside arthroscopic reconstruction of ATFL with InternalBrace™ for CLAI. MATERIAL AND METHODS We included 108 patients who underwent all-inside arthroscopic ATFL reconstruction with InternalBrace™ for CLAI from January 2018 to April 2020 through a retrospective study. Patients age ranged from 19 to 58 years (mean 35.6±8.7 years). Several elements are used to evaluate the clinical consequences of ankle function, including the American Orthopedic Foot and Ankle Society (AOFAS), Japanese Society for Surgery of the Foot Ankle-Hindfoot (JSSF), Kofoed, Tegner scores and complications, and the tilt angle of talus (TT) and the anterior displacement of talus (ADT) with stressing radiographs were taken to measure in follow-ups. RESULTS All 108 patients had all-inside arthroscopic procedures performed smoothly without serious complications. During the follow-up period (26.7±2.6 months on average), no recurrence of ankle instability and other serious complications happened. The AOFAS, JSSF, Kofoed, and Tegner scores significantly increased as time went by postoperatively, which proved statistically significant (P<0.01). Regarding stress-radiographic measurements, TT significantly decreased from (9.5±1.1)° preoperatively to (2.6±0.6)° at the latest follow-up (P<0.01), while ADT significantly decreased from (9.5±1.0) mm preoperatively to (2.6±0.6) mm at the latest examination (P<0.01). CONCLUSIONS All-inside arthroscopic ATFL reconstruction with the InternalBrace™ for CLAI is beneficial for ankle stability, allowing earlier return to activities.

[Release of Exosomes Derived from Leukocyte-Depleted Red Cell Suspension and Its Regulation on Hematological Tumor Cells].

OBJECTIVE: To investigate the release of exosome (Exo) from leukocyte-depleted red cell suspension (LDRCS) at different storage time and its regulation on proliferation of hematological tumor cells and possible mechanism. METHODS: The Exo (RBC-Exo) in LDRCS at different storage time was obtained by ultracentrifugation, and the morphology and immunological marker of RBC-Exo were detected by transmission electron microscopy and Western blot, respectively. The particle size distribution of RBC-Exo in LDRCS at different storage time was detected by Dynamic Light Scattering. CCK-8 assay was used to explore the effect of RBC-Exo on hematological tumor cell proliferation. Western blot was used to detect the expression of proliferation-related proteins in hematological tumor cells after co-culture with RBC-Exo. RESULTS: RBC-Exo was isolated, which was characterized by cup-like shape, particle size distribution ranged from 20 to 200 nm, CD63/TSG101 enriched, Calnexin negative, CD235a positive and CD41 negative. The particle size distribution of RBC-Exo from LDRCS between middle was not significantly different and late stored stage. But the particle size distribution of RBC-Exo at middle-late stored stage(>14 d) was larger than that at early stored stage (≤14 days). Compared with the control group, RBC-Exo could significantly promote the proliferation of HBL1, U2932 and Jurkat cells. Compared with the control group, the cycle-related protein P21 was significantly down-regulated in HBL1, U2932 and Jurkat cells after co-culture with RBC-Exo for 3 days, while the anti-apoptotic protein BCL-2 was not changed significantly. CONCLUSION: The morphology of RBC-Exo from LDRCS at middle-late stored stage was different from that at early stored stage. RBC-Exo could promote the proliferation of hematological tumor cells, possibly by regulating the expression of cycle-associated protein P21.

Plasma Extracellular Vesicle Long RNAs Have Potential as Biomarkers in Early Detection of Colorectal Cancer.

Background: Early detection of colorectal cancer (CRC) is crucial to the treatment and prognosis of patients. Traditional screening methods have disadvantages. Methods: 231 blood samples were collected from 86 CRC, 56 colorectal adenoma (CRA), and 89 healthy individuals, from which extracellular vesicle long RNAs (exLRs) were isolated and sequenced. An CRC diagnostic signature (d-signature) was established, and prognosis-associated cell components were evaluated. Results: The exLR d-signature for CRC was established based on 17 of the differentially expressed exLRs. The d-signature showed high diagnostic efficiency of CRC and control (CRA and healthy) samples with an area under the curve (AUC) of 0.938 in the training cohort, 0.943 in the validation cohort, and 0.947 in an independent cohort. The d-signature could effectively differentiate early-stage (stage I-II) CRC from healthy individuals (AUC 0.990), as well as differentiating CEA-negative CRC from healthy individuals (AUC 0.988). A CRA d-signature was also generated and could differentiate CRA from healthy individuals both in the training (AUC 0.993) and validation (AUC 0.978) cohorts. The enrichment of class-switched memory B-cells, B-cells, naive B-cells, and mast cells showed increasing trends between CRC, CRA, and healthy cohorts. Class-switched memory B-cells, mast cells, and basophils were positively associated with CRC prognosis while natural killer T-cells, naive B-cells, immature dendritic cells, and lymphatic endothelial cells were negatively associated with prognosis. Conclusions: Our study identified that the exLR d-signature could differentiate CRC from CRA and healthy individuals with high efficiency and exLR profiling also has potential in CRA screening and CRC prognosis prediction.

[Research Advances on Abnormal Secretion and Function Abnormality of Exosomes Derived from Lymphoma Cells Caused by Latent EB Virus--Review].

Abstract　　The Latent infection cansed by Epstein-Barr virus (EBV) closely relates with the occurrence and development of several kinds of lymphoma. Exosome (EXO) is functional bilayer membrane structural corpuscles which are secreted by cells contain proteins, lipids and nucleic acids. In recent years, researches showed that EXO play an important role in the occurrence and development of tumors. Therefore, the resenrches which compare the differences in quantity and contents of EXO secreted by cells between EBV negative lymphoma and EBV positive lymphoma and the clarify the influence of EXO on biological behaviors of lymphoma cells and immune cells have the important, significance for understanding the mechanisms related with effect of latent EBV on the occurrence and development of lymphoma by exosome pathway. This review focuses on research progress about the effect of latent EBV on amounts, contents and functions of EXO secreted by lymphoma cells.

[Arginase Level in Apheresis Leukocyte-Reduced Platelets Stored for Different Time].

OBJECTIVE: To explore the effect of storage time on arginase level and possible source of arginase in apheresis leukocyte-reduced platelets(ALR-Plt). METHODS: The arginase level and myeloperoxidase(MPO) levels in ALR-Plt and control plasma were detected by ELISA. The relationship between arginase level and MPO level in ALR-Plt was analyzed by correlation analysis. RESULTS: There was no significant difference of arginase level between ALR-Plt stored less than 3 days and control plasma. However, arginase level in ALR-Plt stored over 3 days was significantly higher than that in ALR-Plt stored less than 3 days and control plasma(P<0.05). There was no significant difference of MPO level in ALR-Plt stored for different times, but the MPO level in ALR-Plt stored for different time was lower than that in control plasma. Correlation analysis showed that arginase level positively correlated with MPO level in ALR-Plt of different storage time (r=0.58). CONCLUSION: The arginase level in ALR-Plt stored over 3 days increase significantly. The main possible source of arginase in ALR-Plt is the residual white blood cells, especially neutrophils.

miR-203 inhibits cell growth and regulates G1/S transition by targeting Bmi-1 in myeloma cells.

The oncogene B-cell-specific Moloney murine leukemia virus insertion site­1 (Bmi­1) is overexpressed in multiple myeloma (MM). Our previous study demonstrated that Bmi­1 silencing sensitized MM cells to bortezomib. Translational regulation has emerged as a prominent underlying mechanism of Bmi­1 regulation, particularly via microRNA targeting. The present study determined that Bmi­1 may be directly targeted by miR­203 using a luciferase assay. In addition, enforced expression of miR-203 led to significant downregulation of Bmi­1 protein and mRNA expression levels. Furthermore, restoration of miR-203 significantly inhibited cell growth and G1/S transition in MM cells. miR­203 was downregulated in MM patients, and a negative correlation between the expression of miR­203 and Bmi­1 was observed. The results of the present study indicated that miR­203 exerts growth­inhibiting effects in MM through the suppression of Bmi­1 expression. In conclusion, the present study demonstrated that Bmi­1 is a direct functional target of miR-203 in MM.

miR-299-5p promotes cell growth and regulates G1/S transition by targeting p21Cip1/Waf1 in acute promyelocytic leukemia.

MicroRNAs (miRs) are often located in genomic breakpoint regions and are hypothesized to be important regulators involved in the regulation of critical cell processes, including cell apoptosis, proliferation and differentiation. miR-299 has been reported to be upregulated in acute promyelocytic leukemia (APL); however, the function and mechanistic role of miR-299 in APL remains unknown. The present study demonstrated mir-299 significantly induced cell growth and cell cycle progression at the G1/S transition in APL cells. Notably, the present study revealed that miR-299-5p induces these effects, whereas miR-299-3p does not. Additional studies demonstrated that in APL cells the tumor suppressor p21Cip1/Waf1 is a downstream target of miR-299; miR-299 binds directly to the 3' untranslated region of p21Cip1/Waf1, and reduces protein, but not mRNA, levels of p21Cip1/Waf1. The present findings demonstrate that miR-299 exerts growth-promoting effects in APL cells through the suppression of p21Cip1/Waf1. Overall, the present study demonstrates that p21Cip1/Waf1 is a direct functional target of miR-299 in APL.

[Arginase Level in Suspended Red Blood Cells Storaged for Different Time].

OBJECTIVE: To explore the effect of storage time on arginase level, and the possible source of arginase in suspended red blood cells (RBC). METHODS: The arginase and myeloperoxidase (MPO) levels in suspended RBC and control plasma were detected by ELISA. The free hemoglobin level in suspended RBC and control plasma were detected by colorimetric method. The relationship between arginase level, MPO level and free hemoglobin level in suspended RBC was analyzed by the related methods. RESULTS: The arginase and free hemoglobin levels in suspended RBC were higher than those in control plasma. Otherwise, MPO level was not significantly different between suspended RBC and control plasma. All of them did not increase along with prolonging of storage time. There was not a significant correlation between arginase level and free hemoglobin level in suspended RBC of different storage time (r = 0.03), but arginase level positively correlated with MPO level in the suspended RBC of different storage time (r = 0.76). CONCLUSION: The arginase level in suspended RBC storaged for different time increases significantly, but not along with prolonging of storage time. The main possible source of arginase in the suspended RBC is the residual white blood cell, especially neutrophils.

[Expression and Clinical Significance of Bmi-1 and P14 in Extranodal NK/T-cell Lymphoma].

OBJECTIVE: This study was aimed to investigate the expression and clinical significance of Bmi-1 and P14 in extranodal NK/T-cell lymphoma (ENKTCL) tissue. METHODS: Maxvision immunohistochemistry technique was used to detect the expression level of Bmi-1 and P14 in the tissues of 21 patients with ENKTCL and 11 normal lymph nodes. The correlation of Bmi-1 or P14 expression with the clinical features and the correlation between Bmi-1 and P14 expression were analyzed. RESULTS: The expression of Bmi-1 protein was higher in tissues of ENKTCL than that in tissues of lymph nodes, and the Bmi-1 expression levels did not correlate with patients' sex, age, lactate dehydrogenase (LDH), International Prognostic Index (IPI) scores and B symptoms (P > 0.05), except for clinical stage (P < 0.05). The P14 protein expression level was lower in ENKTCL tissues than in normal lymph node tissues, which did not correlate with age, sex, LDH, IPI scores, clinical stage and B symptoms. Correlation test showed a negative correlation between Bmi-1 and P14 (r = -0.472, P = 0.031). CONCLUSION: Bmi-1 protein over-expresses in ENKTCL tissues that may display a negative-regulation effect on P14 in the genesis and progress of ENKTCL.

[Growth Inhibition of Multiple Myeloma Cells Caused by MicroRNA-15a and Its Mechanisms].

OBJECTIVE: To explore the effect and possible mechanisms of miR-15a on growth of multiple myeloma(MM) cells. METHODS: MM cell lines (U266 and RPMI8226) were transfected by lentiviral particles. MM stable cell lines were selected and collected by flow cytometry (FCM). Proliferation of MM cells before and after miR-15a high expression was detected by CCK-8 method. Apoptosis of MM cells before and after miR-15a high expression was detected by AO/EB dying, Hoechst 33258 dying and FCM, respectively. Cell cycle of MM cells before and after miR-15a high expression was detected by FCM. The expressions of miR-15a, BMI-1 and BCL-2 mRNA of MM cells before and after miR-15a high expression were detected by real-time PCR. The expressions of BMI-1 protein of MM cells before and after miR-15a high expression were detected by Western blot. RESULTS: MM stable cell lines with miR-15a high expression was acquired. CCK-8 result showed that high expression of miR-15a could inhibit growth of MM cells (U266 and RPMI8226). AO/EB dying, Hoechst 33258 dying and FCM testing results showed that high expression of miR-15a could significantly induce apoptosis of MM cells (U266 and RPMI8226). The apoptosis rates of U266 and RPMI8226 cells in high expression group and control group were 90.52% vs 37.08% and 59.40% vs 44.17%, respectively. Meanwhile, FCM testing results showed that high expression of miR-15a could induce G1 arrest of MM cells (U266 and RPMI8226), which proportion of G1 phase were 41.50%±0.64%, 45.31%±0.77%, respectively. Real-time PCR results showed that during the growth inhibition process of MM cells caused by miR-15a high expression, the expression of BCL-2 mRNA decreased, but there was no significant changes in the expression of BMI-1 mRNA, while the expression of BMI-1 protein decreased significantly. CONCLUSION: High expression of miR-15a can induce cell cycle arrest and apoptosis of MM cells, then inhibit their growth. The mechanisms may be related with the negative regulation of BMI-1 and BCL-2 genes in post-transcription level caused by miR-15a.

[Analysis of the efficiency and influence factors of PBSC collection with AutoPBSC and MNC procedure of cell separator].

This study was aimed to analyze the efficiency and influence factors of PBSC collection by an automatic (AutoPBSC procedure) and a semiautomatic apheresis procedure ( MNC procedure) of COBE Spectra cell separators. According to the different objects, A total of 109 apheresis cases were divided into autologous cohort (patient) and allogeneic cohort (donor). The quantity and quality of the collections and the characteristics of apheresis procedure were compared, the yields and influence factors of two cohorts with two kinds of procedures were analyzed respectively. The results showed that the collections of two procedure in patients and donors which processed the similar blood volumes were insignificantly different in MNC%, CD34⁺ %, CD34⁺ cell counts and Hb concentration (P > 0.05) ; the collections by AutoPBSC procedure had got fewer platelets, less product volumes whereas more ACD-A used, longer apheresis time in comparison with MNC procedure (P < 0.05). Correlation analysis indicated that MNC (r = 0.314,P = 0.015) , CD34⁺ cell counts (r = 0.922, P = 0.000) in collections were positively correlated with preahperesis in the autologus cohort by two procedures, CD34⁺ cell counts were correlated with WBC (r = 0.369, P = 0.004) and MNC (r = 0.495,P = 0.000) in collections; MNC (r = 0.896, P = 0.000) was positive correlated with preahperesis by AutoPBSC procedures and CD34⁺ cell counts also (r = 0.666,P = 0.000) by MNC procedure in the allogeneic cohort. Male had got more MNC and CD34⁺ cell counts than female (P < 0.05), age ≤ 40 had got more MNC and CD34⁺ cell counts than age>40 (P < 0.05) in patients by AutoPBSC procedure; age > 40 had got more CD34⁺ cell counts than age ≤ 40 by MNC procedure(P < 0.05). Only male had got more MNC and CD34⁺ cell counts than female (P < 0.05) by MNC procedure in donors. It is concluded that with same amount of blood processing, the PBSC collections from autologous patients and allogeneic donors had got a high degree of uniformly in purity of MNC and purity and concentration of CD34(+) cell counts by two procedure, whereas sex and age imposed more influence on PBSC collection in autologous.

[Temporal-spatial distribution of agricultural diffuse nitrogen pollution and relationship with soil respiration and nitrification].

The soil respiration, nitrification and denitrification processes play an important role on soil nitrogen transformation and diffuse nitrogen loading. These processes are also the chains for soil circle. In this study, the Zhegao watershed located north of Chaohu Lake was selected to explore the interactions of these processes with diffuse nitrogen pollution. The BaPS (Barometric Process Separation) was applied to analyze the soil respiration, nitrification and denitrification processes in farmland and forest. The SWAT (Soil and Water Assessment Tool) simulated the temporal and spatial pattern of diffuse nitrogen loading. As the expanding of farmland and higher level of fertilization, the yearly mean loading of diffuse nitrogen increased sustainably from 1980-1995 to 1996-2012. The monthly loading in 1996-2012 was also higher than that in the period of 1980-1995, which closely related to the precipitation. The statistical analysis indicated that there was a significant difference between two periods. The yearly averaged loading of the whole watershed in 1996-2012 was 10.40 kg x hm(-2), which was 8.10 kg x hm(-2) in 1980-1995. The variance analysis demonstrated that there was also a big difference between the spatial distributions of two periods. The forest soil had much higher soil respiration than the farmland soil. But the farmland had higher nitrification and denitrification rates. The more intensive nitrogen transformation in the farmland contributed to the less diffuse nitrogen loading. As the nitrification rate of farmland was higher than denitrification rate, agricultural diffuse nitrate nitrogen loading would increase and organic nitrogen loading would reduce. The analysis of soil respiration, nitrification and denitrification is helpful for the study of soil nitrogen circle form the aspect of soil biology, which also benefits the control of agricultural diffuse nitrogen pollution.

ShRNA-mediated Bmi-1 silencing sensitizes multiple myeloma cells to bortezomib.

The introduction of bortezomib has resulted in a paradigm shift in the treatment of multiple myeloma (MM) and has contributed to the improved survival of patients with MM. Inevitably, resistance to therapy develops, and thus the clinical efficacy of bortezomib is hampered by drug resistance. The oncogene B-cell­specific Moloney murine leukemia virus insertion site­1 (Bmi-1) has been implicated in the pathogenesis of various human malignancies. Furthermore, RNA interference (RNAi)­mediated Bmi-1 silencing has been shown to sensitize tumor cells to chemotherapy and radiation. The role of Bmi-1 in influencing the response to bortezomib therapy has not been investigated to date. In the present study, Bmi-1 was silenced in two MM cell lines (U266 and RPMI8226) using short hairpin RNA (shRNA) targeting Bmi-1 (shBmi-1). A cell counting kit-8 (CCK-8) assay was performed to analyze cell proliferation and evaluate the 50% inhibitory concentration (IC50) values of bortezomib. Cell cycle progression and apoptosis were analyzed by flow cytometry (FCM), and the mRNA and protein expression of associated genes (Bmi-1, p14, p21, Bcl-2 and Bax) was quantified by RT-qPCR and western blot analysis, respectively. The IC50 values significantly decreased in the cells transfected with shBmi-1 (p<0.05). The depletion of Bmi-1 sensitized the MM cells to bortezomib, which increased the G1 phase duration and enhanced bortezomib­induced apoptosis (p<0.05). The expression of p21 and Bax (apoptosis inducer) was upregulated, whereas that of the anti-apoptotic protein, Bcl-2, was downregulated in the Bmi-1­silenced cells (p<0.05). The depletion of Bmi-1 enhanced the sensitivity of MM cells to bortezomib by inhibiting cell proliferation and inducing cell cycle arrest and apoptosis. Our data suggest that Bmi-1 may serve as an important novel therapeutic target in MM.

Comparison of stroke volume variation with pulse pressure variation as a diagnostic indicator of fluid responsiveness in mechanically ventilated critically ill patients.

OBJECTIVE: To compare the diagnostic accuracy of stroke volume variation (SVV) and pulse pressure variation (PPV) in studies that examined both parameters in the same patient population. METHODS: Literature search was conducted in PubMed, EMBASE, CINAHL, and Google Scholar. Receiver operator characteristic (ROC) curves were examined, and summary ROC curves were plotted. RESULTS: The study was conducted from January to July 2013 in The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China. The meta-analysis of 19 studies published during the years 2005 and 2013 revealed a high degree of diagnostic accuracy of both SVV and PPV in predicting fluid responsiveness. The sensitivity and specificity of both the parameters were observed above 80% in a heterogeneous group of over 850 patients of which 55% responded to fluid challenge. The following values along with 95% confidence interval were noticed: SVV - sensitivity 82 (59-93%) and specificity 84 (62-95%), PPV - sensitivity 84 (62-95%) and specificity 83 (58-94%). Area under the curve values obtained in the pooled analysis were 0.84 (0.79-0.89) for SVV, and 0.88 (0.84-0.92) for PPV. CONCLUSION: Both SVV and PPV exhibit a high degree of diagnostic accuracy in predicting the success or failure of a fluid challenge in hemodynamically unstable critically ill patients under controlled mechanical ventilation.

[MicroRNA-193b expression in newly diagnosed leukemia patients and its significance].

This study was aimed to quantitatively detect the levels of microRNA-193b (miR-193b) in leukemia patients and explore its significance. Real time fluorescent quantitative PCR was used to detect the relative expression level of miR-193b. The expression changes of miR-193b in various types of leukemia were analyzed. Then the relationship among miR-193b expression, parts of laboratory index and the response to chemotherapy was analyzed as well. The results showed that miR-193b expression level in acute promyelocytic leukemia (APL) and chronic myeloid leukemia (CML) patients was not lower than that in normal group (P > 0.05). Except for APL, miR-193b expression level in acute myeloid leukemia (AML) patients was lower than that in normal group (P < 0.05). In AML (except for APL) patients, there was no correlation between white blood cell count (P > 0.05), the expression of CD34 (P > 0.05) and miR-193b expression level, but there was negative correlation between chemotherapy response and miR-193b expression level (P < 0.05). It is concluded that miR-193b expression level may be correlated with susceptibility of cells to chemotherapy in AML (except for APL) patients. miR-193b maybe become a new target in AML (except for APL) therapy.

[Expression of MCL-1 and microRNA-29a in extranodal NK/T-cell lymphoma tissue].

This study was aimed to explore the expression level and correlation of MCL-1 and miR-29a in extranodal NK/T-cell lymphoma (ENKTCL) tissue. Maxvision immunohistochemistry technique and real time fluorescent quantitative PCR were used to detect the expression level of MCL-1 and miR-29a in tissue of 20 patients with ENKTCL and 10 patients with proliferative lymphadenitis, respectively. The results showed that the expression of MCL-1 protein were higher in patients with ENKTCL than that in patients with proliferative lymphadenitis, but there were no significant correlation between MCL-1 overexpression and age, sex, Ann Arbor stage and International Prognostic Index (IPI), respectively. Correlation analysis indicated that there was significant negative correlation between miR-29a expression and MCL-1 expression (r = -0.59, P = 0.016). It is concluded that miR-29a may target MCL-1 gene, regulate its expression, then participate in tumorigenesis and development of ENKTCL.

[Mechanism associated to enhancing the sensitivity of myeloma cells U266 to bortezomib by 2-methoxyestradiol].

This study was aimed to explore the synergistic effect of 2-methoxyestradiol (2-ME2) and bortezomib (Bor) on the proliferative inhibition and apoptosis of U266 cell line and its possible mechanism. The cells were treated with 2-ME2, Bor alone and 2-ME2 combined with Bor, respectively. The cell viability and proliferative curve were detected by CCK8, the cell apoptosis was detected by caspase 3/7 activity test, cell cycle status was analyzed by flow cytometry, and real-time PCR was used to detect the mRNA expression of P21, BAX and BCL-2. The results showed that compared with cells treated with 2-ME2 or Bor alone, the proliferative potential of cells in combination group was significantly inhibited (p < 0.05), and apoptosis rate markedly increased (p < 0.05), cell cycle was arrested at G(1)-S phase, the mRNA expressive level of P21 and BAX increased, while the expression of BCL-2 decreased. It is concluded that 2-ME2 combined with Bor synergistically inhibits cell proliferation and induces apoptosis in U266 cell line. The possible mechanism may be associated with its effect of up-regulating P21 and BAX expressions.

[april mRNA expression in newly diagnosed leukemia patients].

This study was aimed to quantitatively detect the levels of april mRNA expression in leukemia patients so as to provide theoretical basis for the target therapy directing at april in leukemia. Real time fluorescent quantitative PCR was used to detect the relative expression level of april mRNA in newly diagnosed leukemia patients and to analyze the changes of its expression level in various type of leukemia. The results showed that the april mRNA expression level in acute leukemia (AL) patients was significantly higher than that in normal controls, there was statistical difference between them (p < 0.05); april mRNA expression level in acute myeloid leukemia (AML) patients was significantly higher than that in normal controls (p < 0.05) and positively correlated with white blood cell count ≥ 20.0 × 10(9)/L (p < 0.05), but not related with extramedullary infiltration and the expression of CD34. Except for acute promyelocytic leukemia (APL), april mRNA expression level was negatively correlated with sensitivity of patients to chemotherapy. april mRNA expression levels in acute lymphoid leukemia (ALL) and chronic myeloid leukemia (CML) patients were not higher than that in normal controls, there was no statistical difference between them (p > 0.05). It is concluded that april gene overexpression exits in AML patients. APRIL protein produced by AML cells probably plays an important role in abnormal proliferation and drug-resistance of AML cells.