BNT12, a novel hybrid peptide of opioid and neurotensin pharmacophores, produces potent central antinociception with limited side effects.

The development of multitarget opioid drugs has emerged as an attractive approach for innovative pain management with reduced side effects. In the present study, a novel hybrid peptide BNT12 containing the opioid and neurotensin (NT)-like fragments was synthesized and pharmacologically characterized. In acute radiant heat paw withdrawal test, intracerebroventricular (i.c.v.) administration of BNT12 produced potent antinociception in mice. The central antinociceptive activity of BNT12 was mainly mediated by µ-, δ-opioid receptor, neurotensin receptor type 1 (NTSR1) and 2 (NTSR2), supporting a multifunctional agonism of BNT12 in the functional assays. BNT12 also exhibited significant antinociceptive effects in spared nerve injury (SNI)-neuropathic pain, complete Freund's adjuvant (CFA)-induced inflammatory pain, acetic acid-induced visceral and formalin-induced pain after i.c.v. administration. Furthermore, BNT12 exhibited substantial reduction of acute antinociceptive tolerance, shifted the dose-response curve to the right by only 1.3-fold. It is noteworthy that BNT12 showed insignificant chronic antinociceptive tolerance at the supraspinal level. In addition, BNT12 exhibited reduced or no opioid-like side effects on conditioned place preference (CPP) response, naloxone-precipitated withdrawal response, acute hyperlocomotion, motor coordination, gastrointestinal transit, and cardiovascular responses. The present investigation demonstrated that the novel hybrid peptide BNT12 might serve as a promising analgesic candidate with limited opioid-like side effects.

miR-196a Upregulation Contributes to Gefitinib Resistance through Inhibiting GLTP Expression.

Tyrosine kinase inhibitor (TKI) therapy has greatly improved lung cancer survival in patients with epidermal growth factor receptor (EGFR) mutations. However, the development of TKI-acquired resistance is the major problem to be overcome. In this study, we found that miR-196a expression was greatly induced in gefitinib-resistant lung cancer cells. To understand the role and mechanism of miR-196a in TKI resistance, we found that miR-196a-forced expression alone increased cell resistance to gefitinib treatment in vitro and in vivo by inducing cell proliferation and inhibiting cell apoptosis. We identified the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) bound to the promoter region of miR-196a and induced miR-196a expression at the transcriptional level. NRF2-forced expression also significantly increased expression levels of miR-196a, and was an upstream inducer of miR-196a to mediate gefitinib resistance. We also found that glycolipid transfer protein (GLTP) was a functional direct target of miR-196a, and downregulation of GLTP by miR-196a was responsible for gefitinib resistance. GLTP overexpression alone was sufficient to increase the sensitivity of lung cancer cells to gefitinib treatment. Our studies identified a new role and mechanism of NRF2/miR-196a/GLTP pathway in TKI resistance and lung tumor development, which may be used as a new biomarker (s) for TKI resistance or as a new therapeutic target in the future.

Label-free and sensitive detection of RNA demethylase FTO with primer generation rolling circle amplification.

We develop for the first time a label-free fluorescent method for sensitive detection of fat mass and obesity-associated protein (FTO) activity using MazF-mediated primer generation rolling circle amplification. This method is very simple with ultrahigh sensitivity and good specificity, and it can detect FTO activity at the single-cell level. Moreover, this method can be applied for the measurement of kinetic parameters and the screening of FTO inhibitors.

NOX4 Signaling Mediates Cancer Development and Therapeutic Resistance through HER3 in Ovarian Cancer Cells.

Development of resistance to therapy in ovarian cancer is a major hinderance for therapeutic efficacy; however, new mechanisms of the resistance remain to be elucidated. NADPH oxidase 4 (NOX4) is responsible for higher NADPH activity to increase reactive oxygen species (ROS) production. In this study, we showed that higher levels of NOX4 were detected in a large portion of human ovarian cancer samples. To understand the molecular mechanism of the NOX4 upregulation, we showed that NOX4 expression was induced by HIF-1α and growth factor such as IGF-1. Furthermore, our results indicated that NOX4 played a pivotal role in chemotherapy and radiotherapy resistance in ovarian cancer cells. We also demonstrated that NOX4 knockdown increased sensitivity of targeted therapy and radiotherapy through decreased expression of HER3 (ERBB3) and NF-κB p65. Taken together, we identified a new HIF-1α/NOX4 signal pathway which induced drug and radiation resistance in ovarian cancer. The finding may provide a new option to overcome the therapeutic resistance of ovarian cancer in the future.

A controlled T7 transcription-driven symmetric amplification cascade machinery for single-molecule detection of multiple repair glycosylases.

Genomic oxidation and alkylation are two of the most important forms of cytotoxic damage that may induce mutagenesis, carcinogenicity, and teratogenicity. Human 8-oxoguanine (hOGG1) and alkyladenine DNA glycosylases (hAAG) are responsible for two major forms of oxidative and alkylative damage repair, and their aberrant activities may cause repair deficiencies that are associated with a variety of human diseases, including cancers. Due to their complicated catalytic pathways and hydrolysis mechanisms, simultaneous and accurate detection of multiple repair glycosylases has remained a great challenge. Herein, by taking advantage of unique features of T7-based transcription and the intrinsic superiorities of single-molecule imaging techniques, we demonstrate for the first time the development of a controlled T7 transcription-driven symmetric amplification cascade machinery for single-molecule detection of hOGG1 and hAAG. The presence of hOGG1 and hAAG can remove damaged 8-oxoG and deoxyinosine, respectively, from the dumbbell substrate, resulting in breaking of the dumbbell substrate, unfolding of two loops, and exposure of two T7 promoters simultaneously. The T7 promoters can activate symmetric transcription amplifications with the unfolded loops as the templates, inducing efficient transcription to produce two different single-stranded RNA transcripts (i.e., reporter probes 1 and 2). Reporter probes 1 and 2 hybridize with signal probes 1 and 2, respectively, to initiate duplex-specific nuclease-directed cyclic digestion of the signal probes, liberating large amounts of Cy3 and Cy5 fluorescent molecules. The released Cy3 and Cy5 molecules can be simply measured by total internal reflection fluorescence-based single-molecule detection, with the Cy3 signal indicating the presence of hOGG1 and the Cy5 signal indicating the presence of hAAG. This method exhibits good specificity and high sensitivity with a detection limit of 3.52 × 10-8 U µL-1 for hOGG1 and 3.55 × 10-7 U µL-1 for hAAG, and it can even quantify repair glycosylases at the single-cell level. Moreover, it can be applied for the measurement of kinetic parameters, the screening of potential inhibitors, and the detection of repair glycosylases in human serum, providing a new paradigm for repair enzyme-related biomedical research, drug discovery, and clinical diagnosis.

Deacetylation-activated construction of single quantum dot-based nanosensor for sirtuin 1 assay.

Sirtuin 1 (SIRT1) is an important histone deacetylase that regulates biological functions ranging from DNA repair to metabolism. The alteration of SIRT1 is associated with a variety of diseases including diabetes, inflammation, aging-related diseases, and cancers. Consequently, the detection of SIRT1 activity is of great therapeutic importance. Herein, we demonstrate for the first time the deacetylation-activated construction of single quantum dot (QD)-based nanosensor for sensitive SIRT1 assay. This nanosensor is composed of a Cy5-labeled peptide substrate and a streptavidin-coated QD. The peptide with one lysine acetyl group acts as both the Cy5 fluorophore carrier and the substrate for sensing SIRT1. In the presence of SIRT1, it removes the acetyl group in the acetylated peptide, and the resultant deacetylated peptide can react with the NHS-activated biotin reagent (sulfo-NHS-biotin) to form the biotinylated peptide. The multiple biotinylated peptides can assemble on single QD surface via biotin-streptavidin interaction, inducing efficient fluorescence resonance energy transfer (FRET) from the QD to Cy5, generating distinct Cy5 signal which can be simply quantified by total internal reflection fluorescence-based single-molecule detection. This single QD-based nanosensor can sensitively detect SIRT1 with a detection limit of as low as 3.91 pM, and it can be applied for the measurement of enzyme kinetic parameters and the screening of SIRT1 inhibitors. Moreover, this nanosensor can be used to detect the SIRT1 activity in cancer cells, providing a powerful platform for epigenetic research and SIRT1-targeted drug discovery.

Study of the Characterization of Side Population Cells in Endometrial Cancer Cell Lines: Chemoresistance, Progestin Resistance, and Radioresistance.

Introduction: Radiotherapy, combined regimens as platinum-paclitaxel chemotherapy and/or endocrine therapy is an important adjuvant treatment after surgery for endometrial cancer (EC). While, the resistance to them remain unclear. In our study, to separate the characteristics of side population (SP) cells from EC cell lines, study the mechanism of Taxol-resistance, progestin resistance and radioresistanc, and provide the basic for EC. Methods: SP cells from EC cell lines HEC-1A, Ishikawa and RL95-2 were separated by Hoechst 33342 staining and flow cytometry analysis. The expression of breast cancer resistance protein (BCRP) in SP cells and non-SP cells from HEC-1A was examined by immunocytochemistry, and the radiation-resistant and Taxol-resistant characteristics of SP cells and non-SP cells were compared by MTS. Ishikawa, Ishikawa-SP, and Ishikawa-non-SP cells incubated with MPA were selected for cell apoptosis assays by using flow cytometry. The expression of caspase-3 was examined by immunocytochemistry, and autophagy was detected by MDC staining. Results: Small proportions of SP cells, namely, 1.44 ± 0.93%, 2.86 ± 3.09%, and 2.87 ± 1.29%, were detected in HEC-1A, Ishikawa and RL95-2, respectively. There was a stronger clone formation efficiency for the SP cells than for non-SP cells in HEC-1A [(6.02 ± 1.17) vs. (0.53±0.20)%, P = 0.001], and there was a significant difference in the rate of tumourigenicity between the SP cells and non-SP cells in HEC-1A (87.5 vs. 12.5%). There were higher levels of BCRP expression (P = 0.001) and resistance to Taxol and radiation (P < 0.05) in the SP cells than in non-SP cells. After MPA treatment, the apoptosis rates were significantly different among the Ishikawa, Ishikawa-SP and Ishikawa-non-SP groups [(4.64 ± 0.18)%, (4.01 ± 0.43)%, and (9.3 ± 0.67)%; (P = 0.05)], and the expression of Caspase-3 in the Ishikawa group was higher than that in Ishikawa-SP group. The autophagic activity of the Ishikawa-SP cells was the strongest, while the autophagic activity of Ishikawa-non-SP was the weakest. Conclusions: There is a significant enrichment in SP cells among different EC cell lines, and these SP cells be more resistant to Taxol, MPA and radiation therapy. The overexpression of BCRP among SP cells may be the cause of resistance to Taxol, progestin and radiotherapy, which may be related to apoptosis and autophagic activity.

SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response.

The TET2 DNA dioxygenase regulates gene expression by catalyzing demethylation of 5-methylcytosine, thus epigenetically modulating the genome. TET2 does not contain a sequence-specific DNA-binding domain, and how it is recruited to specific genomic sites is not fully understood. Here we carried out a mammalian two-hybrid screen and identified multiple transcriptional regulators potentially interacting with TET2. The SMAD nuclear interacting protein 1 (SNIP1) physically interacts with TET2 and bridges TET2 to bind several transcription factors, including c-MYC. SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. TET2 protects cells from DNA damage-induced apoptosis dependending on SNIP1. Our observations uncover a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and many sequence-specific DNA-binding factors. This study also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability.

Simultaneous analysis of 23 illegal adulterated aphrodisiac chemical ingredients in health foods and Chinese traditional patent medicines by ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

This paper presents an application of ultra high-performance liquid-chromatography-quadrupole-TOF high resolution mass spectrometry (UHPLC-Q-TOF HRMS) for simultaneous analysis of 23 illegal adulterated aphrodisiac type chemical ingredients in health foods and Chinese Traditional Patent Medicines (CTPMs). The mass spectrometer was operated in Information Dependent Acquisition (IDA) mode, which provides crucial information for the elemental composition analysis, structure elucidation and quantitative analysis simultaneously. Quantitative analysis was performed using the peak areas of the precursor ions in the XICs. The method validation included assessment of selectivity, sensitivity, calibration curve, accuracy, precision, recovery, matrix effect and stability. The results show good linear relationship with the concentrations of the analytes over wide concentration ranges (e.g., 0.05-10 µg/g for sildenafil) as all the fitting coefficients of determination r2 are >0.9984. The detection limits (LODs) were in the range of 0.002-0.1 µg/g. The recoveries were able to reach 82.5-103.6%, while the matrix effects ranged from 87.7 to 109.3%. The intra- and inter-day accuracies were in the range of 82.3-113.8%, while the intra- and inter-day precision ranged from 0.4 to 13.6%. Among 40 batches of health foods and 32 batches of CTPMs (including 28 capsules, 32 tablets, 10 liquid and 2 pills) samples, 28 batches of heath foods were positive. The detected chemical ingredients involved sildenafil, tadalafil, aildenafil and sulfoaildenafil. This method can be used for the screening, identification and quantification of illegal adulterated aphrodisiac chemical ingredients in health foods and CTPMs. Moreover, the LC-Q-TOF MS is very useful to structural elucidation of unknown compound.

Serum levels of miRNA in patients with hepatitis B virus-associated acute-on-chronic liver failure.

BACKGROUND: Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition and its exact pathophysiology and progression remain unclear. The present study aimed to assess the role of serum miRNAs in the evaluation of HBV-ACLF and to develop a model to predict the outcomes for ACLF. METHODS: Serum was collected from 41 chronic hepatitis B and 55 HBV-ACLF patients in addition to 30 chronic asymptomatic HBV carriers as controls. The miRNAs expressions were measured by real-time quantitative PCR (q-PCR). Statistical analyses were conducted to assess the ability of differentially expressed miRNAs and other prognostic factors in identifying ACLF prognosis and to develop a new predictive model. RESULTS: Real-time q-PCR indicated that serum miR-146a-5p, miR-122-3p and miR-328-3p levels were significantly upregulated in ACLF patients compared to chronic hepatitis B and chronic asymptomatic HBV carriers patients. In addition, multivariate regression analyses indicated that Na+, INR, gastrointestinal bleeding and miR-122-3p are all independent factors that are reliable and sensitive to the prognosis of HBV-ACLF. Therefore, we developed a new model for the prediction of HBV-ACLF disease state: Y = 0.402 × Na+ - 1.72 × INR - 4.963 × gastrointestinal bleeding (Yes = 0; No = 1)-0.278 × (miR-122-3p) + 50.449. The predictive accuracy of the model was 95.3% and the area under the receiver operating characteristic curve (AUROC) was 0.847. CONCLUSIONS: Expression levels of these miRNAs (miR-146a-5p, miR-122-3p and miR-328-3p) positively correlate with the severity of liver inflammation in patients with ACLF and may be useful to predict HBV-ACLF severity.

[Analysis of the Temporal and Spatial Variation of PM2.5 in China Based on the LUR Model].

The land use regression (LUR) model is one of the most important systematic methods to simulate the temporal and spatial differentiation of the atmospheric pollutant concentration. To explore the adaptability of the LUR model to the simulation of air pollutants at the national scale in China and the temporal and spatial variation characteristics of fine air particulate matter (PM2.5) in China in 2015 and its correlation with different geographical elements, we built a LUR model. The LUR model is based on a geographically weighted algorithm using PM2.5 data acquired from the national control monitoring site in 2015 as the dependent variable and applying factors such as the type of land use, altitude, population, road traffic, and meteorological elements as independent variables. Based on model regression mapping, we obtained the distributions of monthly and annual PM2.5 concentrations nationwide in 2015 and analyzed the temporal and spatial variation characteristics of PM2.5 concentrations using the Hu line as a reference line. The results indicate that introducing the geographically weighted algorithm can significantly reduce the residual Moran's Ⅰ of the LUR model, weaken the spatial autocorrelation of residuals, and improve the coefficient of determination R2, which is better to reveal the complex relationship between the spatial distribution and impact factors of PM2.5. Cropland, forest, grass and urban industrial and residential land, and meteorological elements and major roads noticeably impact the PM2.5 concentration. Different spatial distributions of different geographical elements have distinct effects on PM2.5. The PM2.5 shows distinct temporal and spatial differences on both sides of the Hu line. The PM2.5 concentration is relatively high in developed cities with a large population and high industrialization levels. The concentration of PM2.5 is higher in winter and gradually decreases in autumn, spring, and summer.

Preclinical Pharmacokinetics, Tissue Distribution, and Plasma Protein Binding of Sodium (±)-5-Bromo-2-(α-Hydroxypentyl) Benzoate (BZP), an Innovative Potent Anti-ischemic Stroke Agent.

Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (BZP) is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated. For the purpose of investigating the pharmacokinetic profiles, tissue distribution, and plasma protein binding of BZP and Br-NBP, a rapid, sensitive, and specific method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS) has been developed for determination of BZP and Br-NBP in biological samples. The results indicated that BZP and Br-NBP showed a short elimination half-life, and pharmacokinetic profile in rats (3, 6, and 12 mg/kg; i.v.) and beagle dogs (1, 2, and 4 mg/kg; i.v.gtt) were obtained after single dosing of BZP. After multiple dosing of BZP, there was no significant accumulation of BZP and Br-NBP in the plasma of rats and beagle dogs. Following i.v. single dose (6 mg/kg) of BZP to rats, BZP and Br-NBP were distributed rapidly into all tissues examined, with the highest concentrations of BZP and Br-NBP in lung and kidney, respectively. The brain distribution of Br-NBP in middle cerebral artery occlusion (MCAO) rats was more than in normal rats (P < 0.05). The plasma protein binding degree of BZP at three concentrations (8000, 20,000, and 80,000 ng/mL) from rat, beagle dog, and human plasma were 98.1-98.7, 88.9-92.7, and 74.8-83.7% respectively. In conclusion, both BZP and Br-NBP showed short half-life, good dose-linear pharmacokinetic profile, wide tissue distribution, and different degree protein binding to various species plasma. This was the first preclinical pharmacokinetic investigation of BZP and Br-NBP in both rats and beagle dogs, which provided vital guidance for further preclinical research and the subsequent clinical trials.

Oxaliplatin-based combination chemotherapy is still effective for the treatment of recurrent and platinum-resistant epithelial ovarian cancer: results from a single center.

BACKGROUND: Combination paclitaxel and carboplatin is currently a first-line regimen for ovarian cancer. However, many patients develop tumor recurrence or drug resistance to this regimen. The study aims to investigate the effectiveness and safety of an oxaliplatin + epirubicin + ifosfamide regimen for the treatment of recurrent and drug-resistant epithelial ovarian cancer. METHODS: A retrospective analysis of 73 patients with recurrent and drug-resistant ovarian cancer was performed; 38 cases of them received oxaliplatin + epirubicin + ifosfamide regimens (IAP group), 35 patients received non-oxaliplatinbased chemotherapy regimens (control group). The therapeutic effects and side effects of the oxaliplatin + epirubicin + ifosfamide regimen were analyzed and summarized. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare progression-free and overall survival between the two groups. RESULTS: Of the 38 patients in the IAP group, 14 patients (36.84%) achieved complete remission, 12 (31.58%) achieved partial remission, 2 (5.26%) achieved stable disease and 10 (26.32%) developed progressive disease. The overall effective rate (complete or partial remission) of the IAP regime was 68.42%. While, of the 35 patients in the control group, 12 patients (34.29%) achieved complete remission, 3 (8.57%) achieved partial remission, 5 (14.29%) achieved stable disease and 15 (42.86%) developed progressive disease. The overall effective rate was 42.86%, which was lower than that in the IAP group (P = 0.035, χ(2) = 4.836). Progression-free survival was 9.5 months (0-64 months) in the IAP group vs. 3 months (0-74 months) in the non-oxaliplatin group (P = 0.014 by Kaplan-Meier survival curves; HR = 2.260; 95%CI 1.117-4.573; P = 0.023 by Cox proportional hazards regression). Median overall survival was 46 months (9-124 months) in the IAP group vs. 35 months (9-108 months) in non-oxaliplatin group (P = 0.018 by Kaplan-Meier survival curves; HR = 2.272; 95%CI 1.123-4.598; P = 0.022 by Cox proportional hazards regression). In IAP group, 15.79% (6/38) of the patients suffered grade III-IV bone marrow arrest. The main non-hematological side effects of the IAP regimen included nausea and vomiting (21.05%, 8/38), peripheral neurotoxicity (15.79%, 6/38) and hepatic or renal lesions (2.63%, 1/38). The main side effects of the two chemotherapy regimens showed no statistical difference. CONCLUSION: The oxaliplatin-based IAP regimen is potentially effective for salvage chemotherapy in patients with recurrent and drug-resistant ovarian cancer, with a better therapeutic effect and tolerable side effects.

[Study of mechanism of medroxyprogesterone 17-acetate on the cancer stem cell-like properties of human endometrial cancer].

OBJECTIVE: To explore the mechanism resistance of medroxyprogesterone 17-acetate(MPA) on the endometrial cancer side-population(SP) cells. METHODS: (1) Ishikawa-SP cells from endometrial cancer cell lines Ishikawa were be separated by Hoechst 33342 dyeing method and flow cytometry analysis. The clone formation efficiency between Ishikawa-SP cells and Ishikawa-non-SP cells were performed by clone formation assay. Breast cancer resistance protein (BCRP) was examined by immunocytochemistry method. (2) Ishikawa, Ishikawa-SP, Ishikawa-non-SP cells were treated with various concentrations of MPA at 5, 10, 15, 20 µmol/L. After cultured for 24, 48, and 72 hours, cells growth were measured by methanethiosulfomate (MTS) assay. (3) The groups of Ishikawa, Ishikawa-SP, Ishikawa-non-SP cells incubated with MPA at the half maximal inhibitory concentration (IC50) were selected for cell apoptosis assay by using flow cytometry. After MPA treatment, the expression of caspase-3 was examined by immunocytochemistry method. RESULTS: (1) There were few proportion of Ishikawa-SP cells in Ishikawa endometrial carcinoma, which were 2.7%. There were stronger clone formation efficiency for Ishikawa-SP cells than that for Ishikawa-non-SP cells in Ishikawa [(6.02 ± 1.17)% vs.(0.53 ± 0.20)%, P = 0.001]. And there were higher level expression of BCRP (P = 0.001) and also more resistant Taxol and radiation between Ishikawa-SP cells and Ishikawa-non-SP cells. (2) The inhibitory effect of MPA was concentration-dependent and time-dependent. (3)After MPA treatment, the apoptosis rates of Ishikawa-SP, Ishikawa-non-SP,Ishikawa were (4.01 ± 0.43) %, (9.30 ± 0.67) %, and (4.64 ± 0.18) %, respectively(P < 0.05). The level expression of caspase-3 in Ishikawa group after MPA treated were higher than that in Ishikawa-SP group. CONCLUSION: MPA may be inhibit the growth of endometrial cancer, Ishikawa-SP and Ishikawa-non-SP cells, while Ishikawa-SP may be more resistant to MPA than Ishikawa-non-SP, which mechanism of resistance on MPA may be related to the properties of cancer stem-like cells and cell apoptosis.

[Analysis of cardiotoxicity of chemotherapy in 30 cases with gynecological cancer].

OBJECTIVE: To investigate the occurrence of cardiotoxicity of chemotherapeutic drugs in gynecological cancer patients without heart disease, and patients with coronary heart disease or congenital heart disease for providing a basis for the clinical prevention of heart side effects during chemotherapy. METHODS: Thirty cases with gynecological cancer complication with or without coronary heart disease or congenital heart disease before or during chemotherapy admitted from Jan.2004 to Dec.2010 were retrospectively analyzed. RESULTS: For all 30 patients, there were heart failures in 3 cases (10%, 3/30), myocardial infarction in 3 cases (10%, 3/30), angina pectoris in 1 cases (3%, 1/30), ST-T or T-wave changes in 9 cases (30%, 9/30), and arrhythmia in 8 cases (27%, 8/30). CONCLUSIONS: Cancer chemotherapy drugs to the heart may produce an immediate or long-term toxicity, in which could significantly effects on the survival and prognosis of patients. It is very important to prevent the occurrence of cardiotoxicity of chemotherapeutic drugs in gynecological cancer patients with heart diseases during chemotherapy.

[Effects of Zn2+ doping on the structural and luminescent properties of GdTaO4 : Eu3+ phosphors].

GdTaO4 : Eu0.1 phosphors with different concentrations of Zn2+ dopant were synthesized by the solid-state reaction at high temperature. The present paper mainly focused on the effects of Zn2+ on the crystallization behavior, morphology and photoluminescence (PL) properties of GdTaO4 : Eu3+. The synthesized materials were characterized by X-ray diffraction (XRD), scanning electronic microscopy (SEM), PL excitation and emission spectra, decay time curves, etc. Results suggested that the co-doping of Zn2+ could remarkably improve the PL intensity of GdTaO4 : Eu0.1, and there were two maxima in the curve of Eu3+ PL intensity at 611 nm vs Zn2+ doping concentration x. When x = 0. 01 the intensity was improved up to 2.7 times that of pure GdTaO4 : Eu3+, which could be attributed to the creation of oxygen vacancies for the charge neutrality and the alternation of the local environment of activator Eu3+ ions resulting from the incorporation of Zn2+ ions; the other was enhanced up to 3.2 times at x = 0.13 which was due to the flux effect of Zn2+ ions. But ZnO and GdTa7O19 were observed in an excessive Zn2+ doping range (x > 0.13), which resulted in the decrease in the PL brightness and lengthening of decay time. Meanwhile, primary results indicated that the PL intensity of GdTaO4 : Eu0.1, Zn0.13 could be further strengthened by the co-doping of Li+ and K+ ions.