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BaTiO3, BiFeO3 and BiFeO3/BaTiO3 polycrystalline films were prepared by the radio frequency magnetron sputtering on the Pt/Ti/SiO2/Si substrate. The phase structure, converse piezoelectric coefficient and domain structure of BaTiO3, BiFeO3 and BiFeO3/BaTiO3 thin films are characterized by XRD and PFM, respectively. The converse piezoelectric coefficient d33 of BiFeO3/BaTiO3 thin films is 119.5 pm V−1, which is comparable to that of lead-based piezoelectric films. The large piezoelectric response of BiFeO3/BaTiO3 thin films is ascribed to the low-symmetry T-like phase BiFeO3, because the spontaneous polarization vector of T-like phase (with monoclinic symmetry) BiFeO3 can rotate easily under external field. In addition, the reduced leakage current and major domains with upward polarization are also attributed to the large piezoelectricity. [ABSTRACT FROM AUTHOR]

Polymer based composites with high dielectric constant were successfully fabricated using BaTiO3 nanowires with high aspect ratio as inorganic filler and PVDF-HFP as polymer matrix. PVDF-HFP/BaTiO3 nanoparticles composites were also prepared as a contrast. The BaTiO3 nanowires were synthesized via one-step hydrothermal method. The BaTiO3 nanowires and its two types of composites were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. For the composites, breakdown strength measurements, tensile tests and broadband dielectric spectroscopy analyses were also carried out. The results show that the two types of fillers are homogeneously dispersed in the matrix. The dielectric constant of composites filled by BaTiO3 nanowires is larger than that filled by BaTiO3 nanoparticles at the same content. Stronger interfacial polarization was found in PVDF-HFP/BaTiO3 nanowire composites. Two theoretical models were employed to predict the dielectric constants of composites, and the experimental data were consistent with the estimated trend. The enhanced dielectric properties of PVDF-HFP/BaTiO3 nanowire composites are attributed to the superior interfacial polarization and high aspect ratio of BaTiO3 nanowires. [ABSTRACT FROM AUTHOR]

Background: Infantile haemangiomas (IHs) involving the lip are of special concern because of the susceptibility of complications, including ulceration, obstruction and disfigurement. The available data for the relationship between their clinical characteristics and ulcerations are limited., Objectives: To describe the clinical characteristics of lip IHs and to evaluate the main risk factors for ulceration., Methods: A retrospective study was designed that included infants with lip IHs during an 8-year period, the clinical data of participants were collected, and univariable and multivariable logistic models were used to determine the relationships between the clinical characteristics of lip IHs and ulcerations. Location, size and type were investigated as potential independent factors influencing the development of ulceration., Results: A total of 69 lip IHs were identified including 40 girls and 29 boys. Ulcerations were found in 37 (53.6%) lip IHs. Lip haemangiomas experiencing ulceration had a mean size (SD) of 3.49 (2.82) cm 2 compared with 1.08 (0.96) cm 2 for those without ulceration. Twenty-eight (52.8%) of the 53 localized haemangiomas and 9 (56.3%) of the 16 segmental haemangiomas experienced ulcerations. Univariable analyses of all investigated factors revealed significant associations of location and size with increased risk of ulceration, and these significant associations remained after adjusting for sex and age [OR 8.61 (95% CI, 2.24-33.13) and 2.62 (95% CI, 1.46-4.72), respectively]. The duration before ulceration was between 4 and 70 days after the occurrence of lip IHs, with a median of 28 (19.41) days. Most ulcers occurred within 45 days of IH occurrence., Conclusions: Ulceration is a common complication of lip IHs at an earlier stage. A swollen with pale or bright crimson appearance of the lip IH surface could be an important signal of subsequent ulceration. Location of the IH on the lower lip and lip IH size are risk factors for the occurrence of ulceration., (© 2020 European Academy of Dermatology and Venereology.)

Acute promyelocytic leukemia (APL) is an interesting model in cancer research, because it can respond to the differentiation/apoptosis induction therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)). Over the past 5 years, it has been well demonstrated that As(2)O(3) induces a high complete remission (CR) rate in both primary and relapsed APL patients (around 85 to 90%). The side effects are mild to moderate in relapsed patients, while severe hepatic lesions have been found in some primary cases. After CR obtained in relapsed patients, chemotherapy in combination with As(2)O(3) as post-remission therapy has given better survival than those treated with As(2)O(3) alone. The effect of As(2)O(3) has been shown to be related to the expression of APL-specific PML-RARalpha oncoprotein, and there is a synergistic effect between As(2)O(3) and ATRA in an APL mouse model. Cell biology studies have revealed that As(2)O(3) exerts dose-dependent dual effects on APL cells. Apoptosis is evident when cells are treated with 0.5 approximately 2.0 microM of As(2)O(3) while partial differentiation is observed using low concentrations (0.1 approximately 0.5 microM) of the drug. The apoptosis-inducing effect is associated with the collapse of mitochondrial transmembrane potentials in a thiol-dependent manner, whereas the mechanisms underlying APL cell differentiation induced by low dose arsenic remain to be explored. Interestingly, As(2)O(3) over a wide range of concentration (0.1 approximately 2.0 microM) induces degradation of a key leukemogenic protein, PML-RARalpha, as well as the wild-type PML, thus setting up a good example of targeting therapy for human cancers.

Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, in contrast to the mild liver dysfunction in one third of the relapsed patients. Forty of forty-seven (85.1%) relapsed patients achieved CR. Two of three nonresponders showed clonal evolution at relapse, with disappearance of t(15;17) and PML-RARalpha fusion gene in 1 and shift to a dominant AML-1-ETO population in another, suggesting a correlation between PML-RARalpha expression and therapeutic response. In a follow-up of 33 relapsed cases over 7 to 48 months, the estimated disease-free survival (DFS) rates for 1 and 2 years were 63.6% and 41.6%, respectively, and the actual median DFS was 17 months. Patients with white blood cell (WBC) count below 10 x 10(9)/L at relapse had better survival than those with WBC count over 10 x 10(9)/L (P =.038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patients treated with As2O3 combined with chemotherapy, compared with 12 of 18 relapses with As2O3 alone (P =.01). Reverse transcription polymerase chain reaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showed long-term use of As2O3 could lead to a molecular remission in some patients. We thus recommend that ATRA be used as first choice for remission induction in newly diagnosed APL cases, whereas As2O3 can be either used as a rescue for relapsed cases or included into multidrug consolidation/maintenance clinical trials.

Background: Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia via induction of differentiation and programmed cell death (apoptosis). We investigated the effects of As2O3 on a panel of malignant lymphocytes to determine whether growth-inhibitory and apoptotic effects of As2O3 can be observed in these cells at clinically achievable concentrations., Methods: Eight malignant lymphocytic cell lines and primary cultures of lymphocytic leukemia and lymphoma cells were treated with As2O3, with or without dithiothreitol (DTT) or buthionine sulfoximine (BSO) (an inhibitor of glutathione synthesis). Apoptosis was assessed by cell morphology, flow cytometry, annexin V protein level, and terminal deoxynucleotidyl transferase labeling of DNA fragments. Cellular proliferation was determined by 5-bromo-2'-deoxyuridine incorporation into DNA and flow cytometry and by use of a mitotic arrest assay. Mitochondrial transmembrane potential (delta psi(m)) was measured by means of rhodamine 123 staining and flow cytometry. Protein expression was assessed by western blot analysis or immunofluorescence., Results: Therapeutic concentrations of As2O3 (1-2 microM) had dual effects on malignant lymphocytes: 1) inhibition of growth through adenosine triphosphate (ATP) depletion and prolongation of cell cycle time and 2) induction of apoptosis. As2O3-induced apoptosis was preceded by delta psi(m) collapse. DTT antagonized and BSO enhanced As2O3-induced ATP depletion, delta psi(m) collapse, and apoptosis. Caspase-3 activation, usually resulting from delta psi(m) collapse, was not always associated with As2O3-induced apoptosis. As2O3 induced PML (promyelocytic leukemia) protein degradation but did not modulate expression of cell cycle-related proteins, including c-myc, retinoblastoma protein, cyclin-dependent kinase 4, cyclin D1, and p53, or expression of differentiation-related antigens., Conclusions: Substantial growth inhibition and apoptosis without evidence of differentiation were induced in most malignant lymphocytic cells treated with 1-2 microM As2O3. As2O3 may prove useful in the treatment of malignant lymphoproliferative disorders.

The therapeutic effect of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at relapse after all-trans retinoic acid (ATRA) induced and chemotherapy maintained complete remission (CR). As2O3 was administered intravenously at the dose of 10 mg/d. Clinical CR was achieved in nine of 10 (90%) patients treated with As2O3 alone and in the remaining five patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA. During the treatment with As2O3, there was no bone marrow depression and only limited side effects were encountered. Pharmacokinetic studies, which were performed in eight patients, showed that after a peak level of 5.54 micromol/L to 7.30 micromol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors. In addition, increased amounts of arsenic appeared in the urine, with a daily excretion accounting for approximately 1% to 8% of the total daily dose administered. Arsenic contents in hair and nail were increased, and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at CR. On the other hand, a decline of the arsenic content in hair and nail was observed after withdrawal of the drug. We conclude that As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy.

Recent clinical studies in China showed that As2O3 is an effective and relatively safe drug in the treatment of acute promyelocytic leukemia (APL). We found previously that As2O3 can trigger apoptosis of APL cell line NB4 cells, which is associated with downregulation of bcl-2 gene expression and modulation of PML-RAR alpha chimeric protein. To further understand the mechanisms of this alternative therapy for APL, we investigated in this report the effects of a wide range of concentrations of As2O2 on cultured primary APL cells, all-trans retinoic acid (ATRA)-susceptible (NB4 cells) and ATRA-resistant (MR2 subclone) APL cell lines. The results indicated that As2O3 had dose-dependent dual effects on APL cells: inducing preferentially apoptosis at relatively high concentrations (0.5 to 2 micromol/L) and inducing partial differentiation at low concentrations (0.1 to 0.5 micromol/L). The rapid modulation and degradation of PML-RAR alpha proteins, which was induced by As2O3 at 0.1 to 2 micromol/L, could contribute to these two effects. Bone marrow and peripheral blood examination showed that myelocyte-like cells, probably as a result of partial in vivo differentiation, and degenerative cells increased after 2 to 3 weeks of continuous in vivo As2O3 treatment when leukemic promyelocytes decreased. In conclusion, combination of induction of apoptosis and partial differention could be the main cellular mechanisms of As2O3 in the treatment of APL, and PML-RAR alpha could play an important role in determining the specific effects of As2O3 on APL cells.

It has been shown recently in China that arsenic trioxide (As2O3) is a very effective treatment for acute promyelocytic leukemia (APL). APL patients resistant to all-trans retinoic acid (ATRA) and conventional chemotherapy can still respond to AS2O3. In this study, we addressed the possible cellular and molecular mechanisms of this treatment by using NB4 cells as a model. The results show that: (1) As2O3 triggers relatively specific NB4 cell apoptosis at micromolar concentration, as proved by morphology, histogramic related nuclear DNA contents, and DNA gel eletrophoresis. (2) As2O3 does not influence bax, bcl-x, c-myc, and p53 gene expression, but downregulates bcl-2 gene expression at both mRNA and protein levels. (3) As2O3 induces a significant modulation of the PML staining pattern in NB4 cells and HL-60 cells. The micropunctates characteristic of PML-RAR alpha in NB4 cells dissappear after treatment with As2O3, whereas a diffuse PML staining occurs in the perinuclear cytoplasmic region. In addition, a low percentage of untreated NB4 cells exhibits an accumulation of PML positive particles in a compartment of cytoplasm. The percentage of these cells can be significantly increased after As2O3 treatment. A similar PML staining pattern is observed in apoptotic cells. (4) ATRA pretreatment does not influence As2O3-induced apoptosis. These results suggest that induction of cell apoptosis can be one of the mechanisms of the therapeutic effect of As2O3. Moreover, this apoptosis induction occurs independently of the retinoid pathway and may be mediated, at least partly, through the modulation of bcl-2, as well as PML-RAR alpha and/ or PML proteins.

Twenty-seven patients with malignant lymphoma (14 Hodgkin's disease, 9 histiocytosarcoma, 2 plasmacytoma, 2 lympholeucosarcoma) were treated by Ailin-injection plus Chinese herbal medicine. The latter's composition and dose varied depending on the clinical manifestations. All the patients had stage III and IV lesions. The total remission rate was 70.37% (complete remission 13 patients, partial remission 6 patients, no remission 8 patients). In addition, we also studied the suppressive effect of Ailin on transplanted tumor in vivo (S-180). The suppression rates were 36.09%, 48.80%, 32.67% by three repetitions with an average of 39.18% (P less than 0.002). They were 37.25%, 35.29% on S37 with an average of 36.27% (P less than 0.005). They were 46.53%, 44.56%, 51.35%, 45.95% on Ehrlich ascites tumor cells with an average of 47.09% (P less than 0.001). The clinical and experimental studies suggest that Ailin-1 has no serious side effects and is well tolerated by patients with malignant lymphoma at moderate or advanced stages. No toxic reactions were observed at the clinical dose. In the above combination therapy, the Chinese herbal medicine has obvious supplementary effect in the treatment of the patients' cachexia and immuno-suppression.