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1.
Zhongguo Zhong Yao Za Zhi ; 45(14): 3459-3466, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726062

RESUMO

The present study was performed to establish the UPLC fingerprints of Bolbostemmatis Rhizoma and determine the contents of three saponins by quantitative analysis of multi-components by single marker(QAMS), and provide basis for quality evaluation of Bolbostemmatis Rhizoma. The analysis was carried out on an analytical column of Waters Cortecs T3(2.1 mm×100 mm,1.6 µm)with gradient elution by acetonitrile-0.1% phosphoric acid solution, at a flow rate of 0.3 mL·min~(-1). The detection wavelength was 203 nm, the column temperature was 30 ℃ and the injection volume was 1 µL. The UPLC fingerprints of Bolbostemmatis Rhizoma were established and evaluated by similarity calculation, cluster analysis and principal component analysis. The relative calibration factors of toberoside B and toberoside C were determined with toberoside A as internal reference. The content was calculated by relative calibration factors to develop a method of QAMS. Comparing the results of QAMS with those of ESM, the accuracy and feasibility of one-eva-luation and multi-evaluation can be determined. RESULTS:: showed that the fingerprints of 19 batches of Bolbostemmatis Rhizoma have four common peaks with similarities ranging from 0.754 to 1.000. Cluster analysis and principal component analysis classified 19 batches of Bolbostemmatis Rhizoma into three categories, which was consistent with the similarity evaluation results. The relative deviation between the content of tubeicosides B and C in 19 batches of Bolbostemmatis Rhizoma determined by QAMS and ESM is less than 5.0%, indicating that there was no significant difference between the two methods. Therefore, the UPLC fingerprints combined with QAMS and similarity evaluation can be effectively used to evaluate the quality of Bolbostemmatis Rhizoma.

2.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(7): 696-700, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32669163

RESUMO

OBJECTIVE: To study the reference ranges of platelet and related parameters within 24 hours after birth in preterm infants with different gestational ages. METHODS: According to the inclusion and exclusion criteria, a retrospective analysis was performed for the chart review data of 1 070 preterm infants with a gestational age of 23-36+6 weeks who were admitted to the neonatal intensive care unit from January to December in 2018. The reference ranges of platelet parameters were calculated for the preterm infants within 24 hours after birth. RESULTS: There were no significant differences in platelet count (PLT) and plateletcrit (PCT) among the preterm infants with different gestational ages (P>0.05). The late preterm infants (34-36+6 weeks; n=667) had significantly lower mean platelet volume (MPV) and platelet distribution width (PDW) than the extremely preterm infants (23-27+6 weeks; n=36) and the early preterm infants (28-33+6 weeks; n=367) (P<0.05). There were no significant differences in these platelet parameters between the preterm infants with different sexes (P>0.05). The reference ranges of platelet parameters in preterm infants were calculated based on gestational age. The reference ranges of PLT and PCT were (92-376)×109/L and 0.1%-0.394% respectively, for the preterm infants with a gestational age of 23-36+6 weeks. The reference ranges of MPV and PDW were 9.208-12.172 fl and 8.390%-16.407% respectively, for the preterm infants with a gestational age of 23-36+6 weeks; the reference ranges of MPV and PDW were 9.19-11.95 fl and 9.046%-15.116% respectively, for the preterm infants with a gestational age of 34-36+6 weeks. CONCLUSIONS: The MPV and PDW of preterm infants with different gestational age are different within 24 hours after birth, and it is more helpful for clinical practice to formulate the reference range of MPV and PDW according to gestational age.


Assuntos
Idade Gestacional , Volume Plaquetário Médio , Plaquetas , Humanos , Recém-Nascido , Valores de Referência , Estudos Retrospectivos
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 748-752, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552931

RESUMO

OBJECTIVE: To study the expression of multiple negative costimulatory molecules on peripheral blood T cells in patients with acute myeloid leukemia (AML) and its affection on prognosis. METHODS: The peripheral blood samples from patients with newly diagnosed AML, complete remission (CR), and no-remission (NR) were collected, the expression levels PD-1、VISTA and TIM-3 in CD4+ and CD8+ T cells were detected by flow cytometry , and the clinical data of patients were analyzed. RESULTS: The expression levels of PD-1、VISTA and TIM-3 of CD4+ and CD8+ T cells in the newly diagnosed AML patients were significantly higher than those in control group (P<0.05). The expression levels of PD-1、TIM-3 and VISTA of CD4+ and CD8+ T cells in the CR group were significantly lower than those in newly diagnosed and the NR group (P<0.05). The TIM-3 expression level positively correlated with VISTA expression level of CD4+ and CD8+ T cells in newly diagnosed AML patients (r=0.85 and 0.73). The VISTA and PD-1 expression level of CD4+ T cells in newly diagnosed AML, NR after first induction chemotherapy and high risk patients significantly increased (P<0.05), the TIM-3 expression level of CD8+ T cells in high risk group significantly increased (P<0.05), and the VISTA expression level of CD8+ T cells in CBFß-MYH11 mutation-positive group significantly decreased (P<0.05). CONCLUSION: The expression of PD-1、TIM-3 and VISTA in AML peripheral blood T cells may be involved in the immune escape of AML and can be the targets of treatment for acute myeloid leukemia patients.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 855-860, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552947

RESUMO

OBJECTIVE: To explore the expression and clinical significance of EZH2 in DLBCL patients accompanied by HBV infection. METHODS: The clinicopathological data of 59 patients with DLBCL accompanied by HBV infection in our hospital from February 2015 to October 2017 were analyzed retrospectively. The patients were divided into HBV negative and HBV positive groups by serological testing before surgery. The expression of EZH2 was detected by immumohistochemical staining, and the clinicopathological characteristics and survival were analyzed and compared between these two groups. RESULTS: There were 30 patients (50.8%) in the HBV negative group and 29 patients (49.2%)in the HBV positive group. The differences of age, LDH level and IPI score between two groups were statistically significant (P<0.05). The expression of EZH2 in HBV- positive group was significantly higher than that in the HBV- negative group (P<0.05), where the expression of EZH2 correlated with the expression of the BCL-6 (r=0.282, P<0.05), especially in the GCB-DLBCL (r=0.549, P<0.05). PFS was not significantly different between two groups of HBV (P>0.05), while the PFS in the R-CHOP regimen group was higher than that in the CHOP regimen group (P<0.05). COX multivariate analysis showed that both the chemotherapy regimen without R and the increased level of LDH were the risk factors affecting the prognosis of DLBCL patients (P<0.05). CONCLUSION: EZH2 highly expresses in HBV positive group, suggesting that the significance of EZH2 in DLBCL with HBV infection is worth further explore.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 484-487, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319383

RESUMO

OBJECTIVE: To investigate the prognostic influencing factors of primary central nervous system lymphoma (PCNSL) patients with diffuse large B-cell immunophenotype. METHODS: 42 PCNSL patients with diffuse large B-cell lymphoma treated in our hospital from March 2011 to October 2017 were enrolled. The effects of different treatments on overall survival of patients were analyzied. RESULTS: The analysis for 42 PCNSL patients with diffuse large B-cell immunophenotype showed that there was no affect of their clinical characteristics,such as sex, age, CSF protein content, treatment with and without temozolomide and rituximab on overall survival of the patients(P>0.05). And it was found that active treatment and the application of conventional intrathecal injection and methotrexate in the treatment could effectively prolong the overall survival time of patients. CONCLUSION: Early diagnosis of PCNSL and active standardized treatment can significantly prolong the survival time of patients, and it is further emphasized that the necessity of conventional intrathecal injection to prolong the survival of patients.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Linfócitos B , Humanos , Prognóstico
6.
Biochem Pharmacol ; 175: 113918, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32194056

RESUMO

BACKGROUND: Dexamethasone is widely used in the treatment of joint diseases due to its anti-inflammatory properties. However, it can cause serious adverse effects. The anterior cruciate ligament (ACL) is an important stabilizer of the knee joint. However, the effect of dexamethasone treatment on the ACL is unclear. OBJECTIVE: This study aims to explore the effects of dexamethasone on ACL tissues and cells through in vitro and in vivo experiments. RESULTS: In vitro, we found that after treatment with dexamethasone, human ACL cell apoptosis was increased, type I collagen (COL1A1) content was decreased, mineralization related genes (ENPP1 and ANKH) and calcified nodules were increased, and endoplasmic reticulum stress (ERS) was enhanced. However, ERS inhibitors could significantly inhibit the increase in calcification and the decrease in COL1A1 induced by dexamethasone. In vivo, Wistar rats received the infra-articular injection with dexamethasone (0.5 mg/kg) for 8 weeks. We found that dexamethasone treatment decreased the COL1A1 content and increased the COL2A1 content in the ACL tissues of rats and that chondroid differentiation and mineralization occurred. Meanwhile, the expression of ERS-related proteins was increased. CONCLUSION: Dexamethasone increased the calcification of ACL cells and caused ACL degeneration through ERS, suggesting that long-term treatment with dexamethasone may cause adverse effects on ACL tissue and increase the risk of long-term rupture.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 218-224, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027280

RESUMO

OBJECTIVE: To study the level and clinical value of Th17 cell subset in the peripheral blood of the patients with aplastic anemia (AA). METHODS: Eighty-five patients with aplastic anemia in our hospital from May 2017 to February 2018 were selected. Among them, 51 patients with poor curative effect were enrolled in group A. and the 34 patients with good curative effect were enrolled in group B, the 35 healthy persons were selected as controls. The levels of serum IL-17, IL-6, IL-4 and IFN-ß were analyzed by ELISA; the levels of peripheral blood Th17 cell subset were analyzed by flow cytometry; the expression levels of RORγt and STAT3 mRNA in lymphocytes were analyzed by RT-PCR; the expression levels of RORγt and STAT3 protein in lymphocytes were analyzed by Western blot. RESULTS: There was no significant difference in sex, age, WBC count and complications between group A and group B (P>0.05). Non-severe aplastic anemia (NSAA) in group B accounted for 23 cases, and the NSAA ratio (23/34) was significantly higher than that in group A (20/51) (P<0.05). The Hb level (86.25±7.9 g/L) and Plt count (54.7 ± 6.3×109/L) in group B were significantly higher than those in group A (P<0.05). ELISA showed that the levels of IL-17 and IL-6 in group A were significantly higher than those in control group (P<0.05); the levels of IL-17 and IL-6 in group B were significantly lower than those in group A (P<0.05); the levels of IL-4 and IFN-ß in group A were significantly lower than those in control group (P<0.05); the levels of IL-4 and IFN-ßin group B were significantly higher than those in group A (P<0.05). Flow cytometry showed that the proportion of Th17 cells in peripheral blood of group A was higher than that of group B (P<0.05). RT-PCR showed that the levels of RORγt and STAT3 mRNA in group A were significantly higher than those in control group (P<0.05), and the mRNA levels of RORγt and STAT3 in group B were significantly lower than those in group A (P<0.05). Western blot showed that the protein levels of RORγt and STAT3 in group A were significantly higher than those in control group (P<0.05), and the protein levels of RORγt and STAT3 in group B were significantly lower than those in group A (P<0.05). CONCLUSION: The Th17 cells in peripheral blood of AA patients increase, and the inflammatory reaction in the patients are enhanced. It may be related with the rise of RORγt and STAT3 gene expression, which provides a research direction for clinical treatment of AA.


Assuntos
Anemia Aplástica , Células Th17 , Citometria de Fluxo , Humanos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , RNA Mensageiro
8.
Ecotoxicol Environ Saf ; 189: 110045, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31816499

RESUMO

Phytotoxicity of cadmium (Cd) and its trophic transfer along a terrestrial food chain have been extensively investigated. However, few studies focused on the role of amendments on the trophic transfer of Cd and related mineral nutrients. In a 60-day pot experiment, soil Cd availability, accumulation of Cd, mineral nutrients (Ca and Si) in lettuce, and subsequent trophic transfer along the lettuce-snail system were investigated with or without 3% (w/w) soil amendment (biochar or micro-hydroxyapatite, µHAP). Soil CaCl2 extractable Cd (CdCaCl2) contents decreased by both amendments. µHAP amended soil increased the Freundlich sorption capacity of Cd2+ to a greater extent (15.9 mmol/kg) than biochar (12.6 mmol/kg). Cd, Ca and Si accumulation in lettuce tissues (roots and shoots) varied with amendment species and soil Cd levels. Linear regression analysis showed that root Cd contents are negatively correlated with root Ca and Si contents (r2 = 0.96, p < 0.05). But no significant correlation between shoot Cd and lettuce Ca and Si contents was found (p > 0.05). After 15 days snail feeding, nearly 90% content of Cd was found in snail viscera, while nearly 95% content of Ca was found in snail shells. Contents of Si distributed equally in snail tissues. Biomagnification of Cd, Ca and Si (TF > 1) was found in lettuce shoot - snail viscera system. Opposite tendency of TF variation between Cd and nutrient elements (Ca and Si) from shoots to snail tissues indicated that µHAP, rather than biochar, amendment is applicable to remediate soil Cd contamination in our study.


Assuntos
Cádmio/análise , Carvão Vegetal/química , Alface/efeitos dos fármacos , Minerais/metabolismo , Poluentes do Solo/análise , Solo/química , Animais , Bioacumulação , Cádmio/metabolismo , Cálcio/metabolismo , Cadeia Alimentar , Alface/metabolismo , Silício/metabolismo , Caramujos/efeitos dos fármacos , Caramujos/metabolismo , Poluentes do Solo/metabolismo
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1602-1606, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607319

RESUMO

OBJECTIVE: To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant. METHODS: Seventy-ninth ITP patients enrolled in this study included the glucocorticoid-ineffective patients (19 cases) and glucocorticoid-dependent patients (60 cases). All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab (dexal-methasone 40 mg/d for 4 days per os, ritaximab 100 mg by intravenous infusion at D7, 14, 21 and 28 respectively). The patients after treatment were followed-up for 12 month, and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed. The changes of Treg cell ratio and BAFF, IL-2 and sCD40L levels before and after treatment were detected by flow cytometry and ELISA respectively. RESULTS: The overall response rate (ORR) of patients treated with above- mentioned regemen at 1, 3, 6 and 12 months after treatment was 79.7% (63/79), 69.6% (55/79), 63.3% (50/79) and 60.8% (48/79) respectivcly, out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1, 3, 6 and 12 months after treatment was 47.4% (9/19) vs 90.0% (54/60), 36.8% (7/19) vs 80.0% (48/60), 21.1% (4/19) vs 76.7% (46/60), 21.1% (4/19) vs 73.3% (44/60), and the difference between 2 groups was statistically significant. The detection of T reg cell showed that the T reg cell ratio in glucocorticoid- ineffective and dependent patients at 1, 3, 6 and 12 months after treatment was (1.70±0.43)% vs (3.47±0.72)%, (1.66±0.33)% vs (4.29±0.91)%, (1.71±0.37)% vs (4.44±0.97)%, (3.36±0.54)% vs (4.29±1.04)%, respectively. The detection of cytokines showed that the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased (P<0.05), the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment, but there was no statistical difference as compared with glucocosticoid-depenment patients. CONCLUSION: The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective. The regulatory effect of rituximab on the T-reg cells, BAFF, IL-2 and sCD40L may be one of its mechanisms.


Assuntos
Púrpura Trombocitopênica Idiopática , Rituximab/uso terapêutico , Dexametasona , Glucocorticoides , Humanos , Inosina Trifosfato , Púrpura Trombocitopênica Idiopática/tratamento farmacológico
11.
EJNMMI Res ; 9(1): 89, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511990

RESUMO

BACKGROUND: The aim of this study was to evaluate the prognostic value of positron emission tomography (PET) parameters and the PET texture features of fluorine 18-fluorodeoxyglucose ([18F]FDG) uptake on pretreatment PET/computed tomography (CT) in patients with locally advanced salivary gland carcinoma treated with interstitial brachytherapy. METHODS: Forty-three patients with locally advanced salivary gland carcinoma of the head and neck were treated with 125I interstitial brachytherapy as the sole modality and underwent [18F]FDG PET/CT scanning before treatment. Tumor segmentation and texture analysis were performed using the 3D slicer software. In total, 54 features were extracted and categorized as first-order statistics, morphology and shape, gray-level co-occurrence matrix, and gray-level run length matrix. Up to November 2018, the follow-up time ranged from 6 to 120 months (median 18 months). Cumulative survival was calculated by the Kaplan-Meier method. Factors between groups were compared by the log-rank test. Multivariate Cox regression analysis with a backward conditional method was used to predict progression-free survival (PFS). RESULTS: The 3- and 5-year locoregional control (LC) rates were 55.4% and 37.0%, respectively. The 3- and 5-year PFS rates were 51.2% and 34.1%, respectively. The 3- and 5-year overall survival (OS) rates were 77.0% and 77.0%, respectively. Univariate analysis revealed that minimum intensity, mean intensity, median intensity, root mean square, and long run emphasis (LRE) were significant predictors of PFS, whereas clinicopathological factors, conventional PET parameters, and PET texture features failed to show significance. Multivariate Cox regression analysis showed that minimum intensity and LRE were significant predictors of PFS. CONCLUSIONS: The texture analysis of pretreatment [18F]FDG PET/CT provided more information than conventional PET parameters for predicting patient prognosis of locally advanced salivary gland carcinoma treated with interstitial brachytherapy. The minimum intensity was a risk factor for PFS, and LRE was a favorable factor in prognostic prediction according to the primary results.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1190-1195, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418378

RESUMO

OBJECTIVE: To investigate the relationship of cytogenetic features, clinical characteristics and prognosis in patients with myelodysplastic syndrome. METHODS: The clinical characteristics and prognosis of 236 patients with MDS admitted to the Affiliated Hospital of Xuzhou Medical University from January 2013 to September 2017 were analyzed retrospectively, the follow-up observation and correlation analysis were performed. RESULTS: There were 33 cases of refractory cytopenia with unilateral dysplasia (RCUD), 8 cases of refractory anemia with ring-shaped iron granulocytes (RARS), 70 cases of refractory cytopenia with multiple dysplasia (RCMD), 23 cases of refractory anemia (RA), 46 cases of refractory anemia with excessive blasts (RAEB-1), 48 cases of (RAEB-2), MDS-U 2 cases, simple del(5q) 6 cases. The detection analysis showed that the chromosome abnormality rate and complex chromosome abnormality rate in RAEB group (RAEB-1 + RAEB-2) and in non-RAEB group (RARS+RCMD+RCUD+RA) were 48.94% vs 43.94%, and 18.09% vs 12.69%, respectively, which were no statistically different. The grouping according to IPSS-R and IPSS showed that the chromosome abnormality rate gradually increased along with enhancement of risk stratifi-cation (P<0.05). The cytogenetic characteristics analysis showed that a total of 108 cases had chromosomal abnormalities, the detection rate was 45.76%, Out of 108 cases, 36 cases had complicated karyotypes, accounted for 15.25% of all patients. The types of chromosomal abnormalities mainly include numbers, structural abnormalities and mixed abnormalities. The chromosome abnormality with the highest detection rate was +8, accounted for 30.56% (33/100) of patients with chromosome abnormalities; followed by -7/7q-, del(5q), del(20q), etc. -7/7q-chromosome abnormalities accounted for 29.63% of all karyotypic abnormalities (including -7/7q-chromosome abnormalities alone and other chromosome abnormalities). The median age of the patients with MDS was 61 (13-88) years old, and the male-female ratio was 1.36∶1. Analysis of blood cell characteristics showed that the three lines were reduced or increased to varying degrees. The median WBC count was 2.8 (0.3-267.1)×109/L, the median Hb level was 69 (20-156) g/L, and the median Plt count was 55 (2-1733)×109/L. The 1 year OS rate in 32 cases of chromosome 7 abnormality and 128 cases of normal chromosome was 25% and 44.53%, respectively, the difference was statistically significant (χ2=4.05, P<0.05) . CONCLUSION: Chromosome karyotype is an independent factor affecting the prognosis of patients with MDS. It is important for the diagnosis, treatment and prognosis evalnation of patients with MDS. The overall prognosis of patients with abnormal chromosome 7 is poor. .


Assuntos
Síndromes Mielodisplásicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Citogenética , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
13.
Int J Mol Sci ; 20(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31408956

RESUMO

This paper first reports on the selective separation of volatile fatty acids (VFAs) (acetic and hexanoic acids) using polymer inclusion membranes (PIMs) containing quaternary ammonium and phosphonium ionic liquids (ILs) as the carrier. The affecting parameters such as IL content, VFA concentration, and the initial pH of the feed solution as well as the type and concentration of the stripping solution were investigated. PIMs performed a much higher selective separation performance toward hexanoic acid. The optimal PIM composed of 60 wt% quaternary ammonium IL with the permeability coefficients for acetic and hexanoic acid of 0.72 and 4.38 µm s-1, respectively, was determined. The purity of hexanoic acid obtained in the stripping solution increased with an increase in the VFA concentration of the feed solution and decreasing HCl concentration of the stripping solution. The use of Na2CO3 as the stripping solution and the involvement of the electrodialysis process could dramatically enhance the transport efficiency of both VFAs, but the separation efficiency decreased sharply. Furthermore, a coordinating mechanism containing hydrogen bonding and ion exchange for VFA transport was demonstrated. The highest purity of hexanoic acid (89.3%) in the stripping solution demonstrated that this PIM technology has good prospects for the separation and recovery of VFAs from aqueous solutions.


Assuntos
Ácido Acético/isolamento & purificação , Caproatos/isolamento & purificação , Líquidos Iônicos/química , Membranas Artificiais , Polímeros/química , Ácidos Graxos Voláteis/isolamento & purificação , Modelos Moleculares , Permeabilidade , Compostos de Amônio Quaternário/química
14.
J Thorac Dis ; 11(5): 1799-1808, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31285872

RESUMO

Background: Patients with unprotected left main coronary artery disease (uLMCAD) have high mortality rate due to sudden heart failure and acute myocardial infarction, for which reliable diagnostic biomarkers to detect this disease at an early stage are in urgent need. Circulating microRNAs (miRNAs) have emerged as a class of novel biomarkers for cardiovascular diseases. The purpose of this study was to investigate utility of miRNAs as biomarkers for early detection of uLMCAD. Methods: High-throughput sequencing (NGS) was initially employed to compare circulating miRNA expression profiles in uLMCAD patients to that in patients without coronary artery disease (CAD) to identify candidate miRNA biomarkers. We further validated the expression of candidate miRNAs by quantitative polymerase chain reaction (qPCR) in a larger cohort. Receiver operating characteristic (ROC) analysis with multivariate logistic regression was used to evaluate the diagnostic power of candidate miRNAs individually and combined. Results: MiR-182-5p, miR-199a-5p and miR-5187-5p were found significantly differentially expressed through NGS (fold changes =1.35, 1.65, 0.5, P values =0.018, 0.046, 0.030, respectively, n=5 for both uLMCAD group and non-CAD control group). In a larger cohort (n=27 for uLMCAD patient and n=38 for non-CAD controls), qPCR confirmed that expression of miR-182-5p was up-regulated (2.57-fold, P=0.011) and expression of miR-5187-5p was down-regulated (0.47-fold, P=0.018) in the plasma of uLMCAD patients. ROC analysis with multivariate logistic regression show that miR-182 and miR-5187 have an AUC score of 0.97 and 0.94 respectively, indicating high diagnostic power as biomarkers for uLMCAD. Interestingly, correlation analysis suggests that the expression of two miRNAs were independent to each other. Conclusions: These results suggested that circulating miR-182-5p and miR-5187-5p were suitable diagnostic biomarkers for uLMCAD, both potentially providing diagnostic information for discriminating uLMCAD patients from non-CAD population prior to invasive diagnostic coronary angiography (CAG).

15.
Brain Behav Immun ; 81: 111-121, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31176001

RESUMO

PURPOSE: Elevated catecholamines in the tumor microenvironment often correlate with tumor development. However, the mechanisms by which catecholamines modulate lung cancer growth are still poorly understood. This study is aimed at examining the functions and mechanisms of catecholamine-induced macrophage polarization in angiogenesis and tumor development. EXPERIMENTAL DESIGN: We established in vitro and in vivo models to investigate the relationship between catecholamines and macrophages in lung cancer. Flow cytometry, cytokine detection, tube formation assay, immunofluorescence, and western blot analysis were performed, and animal models were also used to explore the underlying mechanism of catecholamine-induced macrophage polarization and host immunological response. RESULTS: Catecholamines were shown to be secreted into tumor under the control of the sympathetic nerve system to maintain the pro-tumoral microenvironment. In vivo, the chemical depletion of the natural catecholamine stock with 6OHDA could reduce the release of catecholamines within tumor tissues, restrain the function of alternatively activated M2 macrophage, attenuate tumor neovascularization, and inhibit tumor growth. In vitro, catecholamine treatment triggered the M2 polarization of macrophages, enhanced the expression of VEGF, promoted tumor angiogenesis, and these catecholamine-stimulated effects could be reversed by the adrenergic receptor antagonist propranolol. In addition to regulating tumor-associated macrophages (TAM) recruitment, decreasing catecholamine levels could also shift the immunosuppressive microenvironment by decreasing myeloid-derived suppressor cells' (MDSCs) recruitment and facilitating dendritic cells' (DCs) activation, potentially resulting in a positive antitumor immune response. CONCLUSION: Our study demonstrates the potential of adrenergic stress and catecholamine-driven adrenergic signaling of TAMs to regulate the immune status of a tumor microenvironment and provides promising targets for anticancer therapies.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 702-707, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204919

RESUMO

OBJECTIVE: To investigate the predictive value of CD45dimCD117+ phenotype-abnormal cells (hereinafter referred to as "abnormal cells") for relapse and prognosis in adult patients with acute myeloid leukemia (AML) within 2 weeks after the first complete remission (CR1). METHODS: The clinical data of patients with newly diagnosed AML (non-acute promyelocytic leukemia) admitted in our department from July 1, 2014 to June 30, 2017 were analyzed retrospectively, and the relationship between clinical features at the initial diagnosis and the abnormal phenotype cells of CD45dimCD117+ within 2 weeks after CR1 with the prognosis were analyzed. RESULTS: A total of 91 patients with CD45dimCD117+ abnormal cells were detected. The median age was 51 years old, the median WBC count was 11.60×109/L, and the median ratio of bone marrow blast cells was 0.35 at initial diagnosis. According to the FAB classification, 1 (1.1%), 7 (7.7%), 38 (41.7%), 20 (22.0%), 21 (23.1%) and 4 (4.4%) patients were classifice as M0, M1, M2, M4, M5, and M6, respectively. According to the NCCN risk stratification, 30 (33.0%), 51 (56.0%), and 10 (11.0%) patients were determined as good, moderate, and poor prognosis, respectively. The median ratio of abnormal cells within 2 weeks after CR1 was 1.8500 (0.0236-8.0000)%. The median time from initiation of induction therapy to the acquisition of CR was 46 days, median recurrence-free survival time was 319 days, and median overall survival time was 352 days. A total of 45 patients relapsed, of which 14 died; 46 patients did not relapse, of which 3 died. The cutoff of abnormal cells by receiver operating characteristic curve (ROC) analysis was 2.055% (Se=0.733,Sp=0.761). The abnormal cell ratio was>2.055% in 44 patients, the median ratio of abnormal cells was 3.075%, among which 33 patients relapsed and 12 patients died; the abnormal cell ratio was <2.055% in 47 patients, the median ratio of abnormal cells was 1.150%, 12 patients relapsed and 5 patients died. Regression analysis showed that WBC count>50×109/L and abnormal cell ratio>2.055% were independent risk factors for recurrence. The abnormal cell ratio>2.055% group had a 2-year RFS rate of 54.3% and a 2-year OS rate of 52.8%. The abnormal cell ratio<2.055% group had a 2-year RFS rate of 86.6% (P=0.018), and a 2-year OS rate of 85.3% (P<0.05). CONCLUSION: For adult AML patients, CD45dimCD117+ phenotypical abnormal cells ratio>2.055% within 2 weeks after CR1 is an independent risk factor for recurrence, which also is an dverse factor for RFS and OS.


Assuntos
Leucemia Mieloide Aguda , Humanos , Antígenos Comuns de Leucócito , Contagem de Leucócitos , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-kit , Indução de Remissão , Estudos Retrospectivos
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 708-716, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204920

RESUMO

OBJECTIVE: To investigate the effect of stably down-regulating the FMI expression of K562 cells on the sensitivity of K562 cells to Imatinib (IM) and its possible mechanism. METHODS: Western-blot was used to detect the expression of FMI protein in K562 cells and peripheral blood mononuclear cells from the patients with chronic myelogenous leukemia, chronic myeloid blast crisis and healthy volunteers. The specific interference sequences targeting at the human FMI gene were designed and ligated into the lentiviral vector LV3; the three plasmid system-packaged lentivirus particles were used to transfect K562 cells to screen K562 cells that stably down-regulated FMI. CCK-8 assay and flow cytometry were used to determine effect of IM on cell proliferation and apoptosis. The transcription level of FMI and Fz8 in leukemia cells was detected by fluorescent quantitative PCR. The protein expression levels of FMI, Fz8, NFAT1, BCR-ABL and ß-catenin in leukemia cells were detected by Western-blot. RESULTS: The expression of FMI protein could be detected in peripheral blood mononuclear cells of the patients with CML-BC and K562 cells, the FMI expression could not be detected in all the patients with CML-CP and healthy volunteers. The recombinant lentiviral vector LV3/FMI had been successfully constructed the lentivirus was packaged, and the K562 cells stably down-regulating the FMI protein were screened. After stable down-regulation of FMI expression in K562 cells, the proliferation rate of leukemia cells decreased and the apoptosis rate was increased under the same drug concentration. Both the transcription and protein expression levels of Fz8 decreased. The NFAT1 total protein level increased, as well as the nuclear translocation of protein was enhanced. There was no significant change in the expression level of BCR-ABL fusion protein. The expression level of ß-catenin protein decreased. CONCLUSION: After the stable down-regulation of FMI expression, the sensitivity of K562 cells to IM and apoptosis of cells increase, which are performed possibly by inhibiting the FMI-Fz8 signaling pathway and activating the Ca2+-NFAT and Wnt/ß-catenin signaling pathway.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucócitos Mononucleares , Apoptose , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl , Humanos , Mesilato de Imatinib , Células K562
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 717-722, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204921

RESUMO

OBJECTIVE: To explore the role of Ca2+-NFAT signaling pathway in Ph+-ALL drug resistance mediated by bone marrow stromal cells. METHODS: The transcription level of NFAT mRNA in Sup-B15 cells and Ph+ ALL primary cells was detected by polymerase chain reaction. The expression of P-glycoprotein in Sup-B15 cells was detected by flow cytometry. The change of NFAT protein in Sup-B15 cells was detected by Western blot. AnnexinV/7-AAD was used to label cells. Flow cytometry was used to detect cell apoptosis; Fluo 3-AM dye was used to label cells, and flow cytometry used to detect changes of Ca2+ concentration in leukemia cells. RESULTS: NFAT expression could be detected in both Sup-B15 and Ph+ ALL primary cells; P-glycoprotein could not be detected by flow cytometry; CAS could significantly inhibit NFAT protein expression in clinically applied drug concentrations (2.5, 5 µmol/L); Clinically applied concentration of CAS (2.5, 5 µmol / L) has no significant effect on the apoptosis of Sup-B15 cells, while higher concentration of CAS (10 µmol / L) could induce apoptosis of Sup-B15 cells. Bone marrow stromal cells OP9 could, decrease the sensitivity of Sup-B15 cells and Ph+ ALL primary cells to imatinib (IM); After co-culture with bone were marrow stromal cells, the Ca2+ concentration in Sup-B15 cells was enhanced, the levels of NFAT protein and nullear protein in sup-B15 cells also were enhanced. The addition of CAS in co-culture system could inlibit the Ca2+-NFAT signaling pathway, reduce the protective effect of OP9 on Sup-B15 cells.Conclution:The Ca2+-NFAT sigualing pathway, contributes to the survival of Ph+ ALL cells. Bone marrow stromal cells can mediate the resistance of Ph+ ALL cells to IM by activating Ca2+-NFAT signaling pathway.


Assuntos
Células-Tronco Mesenquimais , Leucemia-Linfoma Linfoblástico de Células Precursoras , Células da Medula Óssea , Linhagem Celular Tumoral , Humanos , Mesilato de Imatinib , Fatores de Transcrição NFATC , Transdução de Sinais
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 976-982, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204964

RESUMO

OBJECTIVE: To analyze the incidence of hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation and the factors affecting HC, so as to provide clinical evidence for further treatment of HC. METHODS: The HC of 113 patients after allogeneic hematopoietic stem cell transplantation in Affiliated Hospital of Xuzhou Medical University between the years 2014-2016 was analyzed respectively. All cases of HC were divided into HC group and non-HC(control) group. The follow-up time: from preeonditionig day to 180 d after transplantation. The 10 clinical parameters were selected for univariate analysis with COX regression analysis: sex, age (<25 years and 25 years), primary disease, conditioning regimen with anti-thymoglobulin(ATG), sex-mismatch in recipients, haploidential HSCT, cytomegalovirus (CMV) viremia, EB viremia, graft-versus-host disease (GVHD), and primary disease relapse, the factors significant at the 0.1 level in univariate analysis should be further evaluated by multivariate analysis using a COX regression analysis. The difference was significant at P<0.05 in multivariate analysis. RESULTS: The HC occured in 31 of 113 patients (27.4%), with 5 cases of grade I (5.5%), 19 of grade II (16.8%), 5 of grade III (4.4%), and 2 of grade IV (1.8%). The median time of HC onset was 37 days (26-70 d) after transplantation. The median duration of HC was 14 days (5-55d). Univariate analysis showed that conditioning with anti-thymoglobulin (ATG) (RR=6.170, 95%CI: 1.875-20.306, P<0.01), CMV viremia (RR=7.633, 95%CI:2.318-25.133) (P<0.01), haploidentical HSCT (RR=0.307, 95%CI:0.137-0.686, P<0.01), GVHD (RR=1.891, 95%CI:0.918-3.898, P>0.05) were the risk factors for recovery from HC. The multivatiate analysis of above-mentioned risk factors with statistical significance showed that only CMV viremia (RR=4.770, 95%CI: 1.394-16.326, P<0.05) was the indentified risk factor affecting the recovery from HC. CONCLUSION: Monitoring CMV viremia and antivirotic treatment are effective measurs to prevent the occurrence of HC and promote the recovery from HC.


Assuntos
Cistite , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco
20.
Int J Biol Macromol ; 136: 209-219, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199972

RESUMO

Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, constitutively active somatic JAK2 mutations were important for the leukemogenesis of acute leukemia (AL). The JAK2 R867Q somatic mutation is detected in a subset of AL patients. However, roles of JAK2 R867Q mutation in the pathogenesis of AL remain unclear. In this study, homology modeling analysis showed that loss of interaction between R867 and Y613 disrupted the JAK2 JH1/JH2 domain's interactions was responsible for its activation. JAK2 R867Q and mutations (R867A and R867G) abolished this interaction caused JAK2 constitutive activation. While, mutations (R867K, Y613E, R867K/Y613E) repairing this interaction reduced JAK2 R867Q mutation's activity. Furthermore, our studies showed that abolished R867 and Y613 interaction disrupted JH1/JH2 domains' interactions and led to JAK2 constitutive activation. More importantly, mutations (R867Q, R867A and R867G) disrupted this interaction enhanced the activity of JAK2-STAT5 pathway and the proliferation of Ba/F3 and MV4-11 cells. Further study showed that JAK2 R867Q mutation promoted the expression of proliferation marker and inhibited the differentiation marker of Ba/F3 and MV4-11 cells. Thus our studies provide clues in understanding the pathogenesis of JAK2 R867Q mutation in AL.


Assuntos
Janus Quinase 2/química , Janus Quinase 2/metabolismo , Leucemia/genética , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Mutação , Doença Aguda , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Humanos , Interleucina-3/farmacologia , Janus Quinase 2/genética , Leucemia/patologia , Modelos Moleculares , Proteínas Mutantes/genética , Redobramento de Proteína , Estrutura Secundária de Proteína/genética , Estrutura Terciária de Proteína/genética
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