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High Q (Hf1−xSnx)O2 ceramics were prepared via a standard solid‐state reaction route, and the microwave dielectric characteristics were investigated systematically together with the structure evolution. With increasing x, the structure changed from HfO2 (monoclinic in space group P21/c, x = 0 and 0.03) to Hf0.77Sn0.23O2 (orthorhombic in space group Pbcn, x = 0.23), while the two‐phase structure: HfO2 major phase and Hf0.77Sn0.23O2 secondary phase, was determined for x = 0.05–0.21, and Hf0.77Sn0.23O2 major phase combined with SnO2 tetragonal secondary phase in space group P42/mnm was confirmed for x = 0.30–0.40. The Qf value was significantly increased from 24,500 to 167,650 GHz by Sn‐substitution, and the best combination of microwave dielectric characteristics was obtained in Hf0.77Sn0.23O2 ceramics: εr = 17.2, Qf = 167 650 GHz at 9.6 GHz and 230 710 GHz at 26.1 GHz, and τf = −52.6 ppm/°C. The dielectric loss was deeply linked with the structure stability and lattice‐distortion. Also, the phase composition, the bond strength, as well as the degree of covalency, had a tight connection with dielectric loss. The present ceramics were expected to be the promising candidates as low‐εr microwave dielectric ceramics. [ABSTRACT FROM AUTHOR]

Ba[(Ca0.2Mg0.2Zn0.2Co0.2Ni0.2)1/3Nb2/3]O3 and Ba[(Mg0.25Zn0.25Co0.25Ni0.25)1/3Nb2/3]O3 perovskite single‐phase ceramics were synthesized by a solid‐state reaction method, and they were annealed at different temperatures in order to investigate the effect of B′‐site configurational entropy on phase stability, ordered domain structure and microwave dielectric characteristics. By comparing the B′‐site high‐entropy composition with B′‐site medium‐entropy and low‐entropy compositions, the entropy‐dominated phase‐stabilization effect and sluggish diffusion effect were observed in Ba[(Ca0.2Mg0.2Zn0.2Co0.2Ni0.2)1/3Nb2/3]O3. These effects enhanced the temperature stability of the B‐site 1:2 ordered structure. Ba[(Ca0.2Mg0.2Zn0.2Co0.2Ni0.2)1/3Nb2/3]O3 even reached a higher Qf value after annealing above the order‐disorder transition temperature (To‐d). This research extends the entropy regulation to ordered complex perovskite and provides a promising way to modify the performances of complex perovskite dielectric ceramics. [ABSTRACT FROM AUTHOR]

(Hf0.25Zr0.25Sn0.25Ti0.25)O2 high‐entropy ceramics were designed and prepared, and their microwave dielectric characteristics were investigated together with the microstructures. The single‐phase structure in space group Pbcn was determined, and the excellent microwave dielectric characteristics were achieved in the present ceramics: εr = 25.6, Qf = 74 600 GHz at 6.5 GHz and τf = −47 ppm/°C. The significant improvement of Qf value was achieved with a prolonged sintering, where the dielectric constant increased slightly while the negative τf decreased in the absolute value at first and then turned to increase. The variation tendency of microwave dielectric characteristics was deeply linked with the microstructure homogeneity, and the introduction of Hf and Sn elements to create the high‐entropy ceramics resulted in the disordered state, and finally led to the improved Qf value. The present work provided an effective approach to achieve enhanced Qf value in microwave dielectric ceramics. [ABSTRACT FROM AUTHOR]

Hf1‐xTixO2 dense ceramics were prepared by a standard solid‐state reaction process, and the microwave dielectric properties in a wide frequency range were determined together with structure evolution. With increasing x, the structure gradually changed from HfO2‐based solid solution (monoclinic in space group P21/c, x ≤ 0.05) to HfTiO4 (orthorhombic in space group Pbcn, x = 0.5), and the two phase regions were determined for 0.1 ≤x < 0.5 and x = 0.55. The microwave dielectric properties of HfO2 ceramics at 10 GHz were determined as εr = 14, Qf = 24 500 GHz, τf = –50 ppm/℃. With Ti‐substitution, the microwave dielectric characteristics, especially the Qf value, could be significantly improved, and the best combination of microwave dielectric characteristics was achieved at x = 0.05: εr = 17, Qf = 84 020 GHz (at 7.8 GHz) and 151 260 GHz (at 27.9 GHz), and τf = –47 ppm/℃. The smallest temperature coefficient of resonance frequency (τf = –4.8 ppm/℃) was obtained for x = 0.55 together with a Qf value of 52 370 GHz at 5.0 GHz and 60 390 GHz at 17.9 GHz, where the dielectric constant was 40. Moreover, Hf1‐xTixO2 microwave dielectric ceramics might be very competitive in the future of mobile communication technology due to their excellent compatibility with Si. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of micro-transplantation in acute myeloid leukemia (AML)., Methods: The clinical data of 13 adult AML patients who received micro-transplantation as consolidation therapy from July 2014 to October 2019 was retrospectively analyzed, and the adverse reactions and efficacy of micro-transplantation were followed up., Results: Eight patients received micro-transpantation were still in complete remission, 5 patients relapsed after micro-transplantation, 1 of them received umbilical cord blood micro-transplantation after remission by reinduction, and all of the 13 patients have survived till now. The median overall survival time was 13 months, and the median relapse-free survival time was 12 months. All 13 patients developed grade 2-4 hematological adverse reactions. The median recovery time of neutrophils and platesets was 13 (11-15) and 15 (13-17) days, respectively. None of the 13 patients developed acute or chronic graft versus host disease. Twelve patients suffered from different infections, however, there were no serious organ function injury complications happened., Conclusion: The micro-transplomtation of HLA-incompatible stem cells derived from peripheral blood or umbilical and blood is an effective regimen for the consolidation therapy of AML, especially for the patients suffered from low and moderate risk of AML or the aged AML patients.

Objective: To investigate the clinical significance of the targeted next-generation sequencing assay for patients with suspected myeloid malignancies., Methods: A total of 39 hematopenia patients with suspected myeloid malignamies in Department of Hematology of The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from January 2018 to April 2019 were treated, 20 hot spot genes of myelodysplastic syndrome (MDS) were detected., Results: Regarding the diagnostic type, there were 7 cases of idiopathic cytopenia of undetermined significance (ICUS), 8 cases of clonal cytopenias of undetermined significance (CCUS) and 24 cases of myeloid myeloid malignancies which included 18 cases of MDS, 4 cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and 2 cases of acute myeloid leukemia. Positive mutation was detected in 70.8% (17/24) of myeloid malignancy patients , and 72.7% (16/22) in MDS and MDS/MPN patients. The main mutation types were ASXL1, TET2 and RUNX1. Compared with gene negative group, there were no significant differences in sex, age (＜60 years old or ≥60 years old), proportion of bone marrow blast cells (＜5% or≥5%) and cytogenetics (good, medium and poor) (P＞0.05). Furthermore, all 8 CCUS patients showed positive mutation, and the incidence of double or multiple mutation in CCUS group was significantly lower than that of the MDS and MDS/MPN group (37.5% vs 54.5%) (P=0.002). The mutation types between the two groups were similar, and there was no significant difference in variant allele frequency (P＞0.05)., Conclusion: Our results suggest that there are high rates of double or multiple mutations in myeloid malignancies, especially in patients with MDS and MDS/MPN. Targeted sequencing assay can improve the diagnosis of myeloid malignancies, and guide clinical treatment.

Objective: To explore the the effects of ubiquitin-proteasome system (UPS) on BCL6 protein level，proliferation and apoptosis of cell imatinib（IM）-resistant K562/G01 cells., Methods: Western blot was used to detect the expression of BCL6 in K562/G01 cells before and after treatment with protease inhibitor MG-132.The RT-PCR and Western blot respectively were used to detect the mRNA and protein expression levels of BCL6 and USP2 in K562/G01 cells treated with or without ML364 (a ubiquitin-specific protease USP2 inhibitor). The effects of IM alone or in combination with ML364 on proliferation and apoptosis of K562/G01 were analysed by CCK-8 method and flow cytometry., Results: After treatment with protease inhibitor MG132, the BCL6 protein level of K562/G01 significantly increased (P<0.05). The mRNA and protein expression level of ubiquitin-specific protease USP2 in K562/G01 cell line was higher than that in K562 cell line (P<0.05). After treatment of K562/G01 with USP2 protease inhibitor ML364, the expression levels of USP2 and BCL6 proteins were down-regulated simultaneously (P<0.05) . After combination of ML364 and IM, both the proliferation inhibitory rate and the apoptosis rate of K562/G01 cells significantly increased(P<0.05)., Conclusion: ML364 decreases the BCL6 protein stability in K562/G01 by inhibiting the USP2-mediated deubiquitination, and down-regulate the BCL6 protein experssion, thereby increases the sensitivity of drug-resistant cells to IM.

Objective: To investigate the effect of homoharringtonine (HHT) on proliferation and apoptosis of CML cell line K562 cells and to explore its possible mechanism through mTOR pathway., Methods: K562 cells were cultured with different concentrations of HHT or in its combination with mTOR inhibitor rapamycin (RAPA) for 24 hours. The cell viability was analyzed by CCK-8 assay, the cell apoptosis was detected by flow cytometry, the expressions of BCL-6, Caspase-3 and mTOR signal pathway related proteins was assayed by Western blot, the expression of BCL-6 mRNA was determined by RT-PCR., Results: The HHT inhibited proliferation and induced apoptosis of K562 cells in a concentration-dependent manner(r=0.970). With the increasing of HHT concentration, the expression level mTOR signal pathway related proteins increased(r=0.908), while the mRNA and protein expression levels of BCL-6 decreased(r mRNA =-0.961, r protein =-0.981), as compared with the HHT alone, the combination of HHT with RAPA could down-regulate the expression of mTOR signal pathway related protein and caspase-3, and up-regulated expression of BCL-6., Conclusion: HHT induces apoptosis of K562 cells by inhibiting BCL-6 expression through mTOR signal pathway.

Objective: To study the effect of homoharringtonine (HHT) alone or combined with 3-methyladenine (3-MA) , an autophagy inhibitor, on the apoptosis and autophagy of K562 cells., Methods: K562 cells were treated with HHT(10 ng/ml) or HHT(10 ng/ml) combined with 3-MA (1.5 mmol/L) for 1 to 8 days. The apoptosis of treated cells was tested by means of flow cytometry(FCM), and the autophagy levels were tested with RT-PCR, Western blot and electron microscopy., Results: In the early stage of HHT-treated group, the apoptosis rate increased and decreased later. Beclin1 mRNA expression level and the LC3II/I ratio were declined firstly and increased later in HHT group. While combining with autophagy inhibitor 3-MA, both the Beclin1 mRNA expression level and the LC3II/I ratio were declined continually during the treated period. The activated caspase-3 protein expression level was also raised sustainability during both HHT and 3-MA cultured period., Conclusions: HHT can induce apoptosis of K562 cells, but the sustaining effect of HHT can induc autophagy of K562 cells, the combination of HHT with 3-MA may enhance the cytotoxicitic effect of HHT on K562 cells.

Tyrosine kinase inhibitors (TKI) have made a dramatic improvement in the clinical efficacy of chronic myelogenous leukemia, but the occurrence of TKL resistance and intolerance does not enable some patients to acquire the satisfactory efficacy. Screening the proper TKL for patients with high risk before the treatment and conversing drug timely based on early detection of TKL resistance are helpful to accurately use TKI and enhance therapeutic efficacy. In this article, the function of some indicators, such as baseline clinical, biochemical and molecular biological characteristics and influence of early treatment response law of imatinib on long-term prognosis of newly diagnosed patients are summarized.

Objective: To explore the effect of homoharringtonine(HHT) combined with imatinib(IM) on proliferation and apoptosis of K562/G01 cells and its potential mechanism., Methods: K562/G01 cells were cultured with HHT and/or IM. CCK-8 assay was used to detect cell proliferation. Cell apoptosis and phosphorylated tyrosine levels were analyzed by flow cytometry. The expression levels of p210, PI3K, p-Akt and Akt protein were determined by Western blot., Results: Compared with HHT or IM alone, drug combination significantly inhibited cell proliferation and induced apoptosis of K562/G01 cells (both P< 0.05). HHT combined with IM could inhibit the levels of phosphorylated tyrosine and phosphorylated Crkl and downregulate the expressions of p210, PI3K and p-Akt in K562/G01 cells., Conclusion: HHT combined with IM can synergistically inhibit proliferation and induce apoptosis of K562/G01 cells by suppressing the p210 expression and its kinase activity.

Objective: To explore the effects of homoharringtonine (HHT) alone or combined with imatinib (IM) on K562 cell proliferation and apoptosis, as well as the mRNA and protein expression of BCL6., Methods: The CCK-8 was used to detect the inhibitory effect of drugs on cell growth, the flow cytometry was used to detect the cell apoptosis. The expression of BCL6 protein was assayed by Western blot, and BCL6 mRNA expression was detected by RT-PCR., Results: HHT alone displayed a proliferation inhibition effect with dose- dependent manner, and induced apotosis; after combination of HHT and IM drugs, both the inhibitory rate and the apoptosis rate were significantly increased compared with the drug alone(P<0.05). Western blot showed that the expression of BCL6 protein was down-regulated after being treated with HHT, however, the BCL6 protein was up-regulated after being treated with IM . The effect of drug combination showed that BCL6 protein significantly down-regulated(P<0.05 ). The expression of BCL6 mRNA was decreased both in the treatment of HHT or IM alone when compared with control. And the effect of drug combination showed that BCL6 mRNA expression was more significantly down-regulated(P<0.05 )., Conclusion: HHT can inhibit the K562 cell proliferation and induce apoptosis of K562 cells. Combination of IM with HHT shows a significant synergistic effect, the mechanism may be associated with down-regulation of BCL6.

Trichinella spiralis and its derivative antigens stimulate T cell activation by inducing dendritic cell semimaturation, thereby regulating the Th1/Th2 type immune response and alleviating or inhibiting allergy and autoimmune diseases. The regulatory T cell and anti-inflammatory factors play important roles in this immunomodulatory process. This article reviews the modulatory effects and their mechanisms of Trichinella spiralis and its derivatives in autoimmune disorders.

Objective: To investigate the killing effect of hypericin on tachyzoites of Toxoplasma gondii RH strain in vitro., Methods: Normal saline （group A） and different concentrations of hypericin (5 μg/ml, group B; 50 μg/ml, group C; 500 μg/ml, group D） were added to T. gondii tachyzoites in 24-well plate（1×10(6)/well）. The tachyzoites were harvested after 2, 4 and 6 h, and underwent the following treatment: trypan blue staining to calculate the dyeing rate, Giemsa staining to observe the morphological and structural alterations of tachyzoites, and transmission electron microscopy to observe the ultrastructure of tachyzoites. In addition, flow cytometry was performed to calculate the survival rate of YFP-carrying Toxoplasma with the same treatment., Results: The trypan blue dyeing rate at 2 h after treatment in groups B, C and D was（11.0±3.6）%, （25.0±6.3）% and（40.0±2.7）% respectively, with a significant difference of group D versus B and C （P<0.01）, and groups C and D versus group A ［（6.0±3.0）%）］. The dyeing rate at 4 h and 6 h in group D was（97.0±2.0）% and （98.0±1.7）%, respectively, both significantly higher than that of groups C ［（30.0±7.2）%, （42.7±5.5）%］, B ［（20.0±3.0）%, （34.0±6.6）%］ and A ［（10.0±1.0）%, （19.3±4.9）%］（P<0.01）. Giemsa staining showed gradual end swelling and necrosis of tachyzoites with increased treatment duration and dosage. Transmission electron microscopy showed swelling of worm body, gap between cell membrane and matrix, increase and enlargement of vacuoles inside worm body, disruption of cell membrane, and dissolving of inner structures, with increased treatment duration. Flow cytometry showed significant difference of tachyzoite survival rate at 2, 4 and 6 h after hypericin treatment with that of the control group（P<0.01）. The survival rate of group C at 2 h after hypericin treatment was（7.9±1.9）%, significantly lower than that of groups B ［（38.1±5.5）%］ and A ［（81.8±6.0）%］ （P<0.01）. No tachyzoite was found to survive in group D at 2 h and in group C at 4 h. The survival rate of group B at 4 and 6 h after hypericin treatment was（14.3±7.9）% and （1.4±1.8）%, respectively, both significantly lower than that of group A［（73.8±11.3）% and（64.1±14.4）%, respectively］ （P<0.01）., Conclusion: Hypericin has a remarkable killing effect on T. gondii tachyzoites, and the efficacy positively correlates with the dose and treatment duration.

Objective: To investigate the effects of AMPK agonist Acadesine (AICAR) on growth inhibition of K562 cells and their sensitivity to imatinib (IM)., Methods: K562 cells were cultured with different concentrations of AICAR alone or its combination with IM for 48 hours, the CCK-8 assay was used to detect cell proliferation, the cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression levels of Cyclin D1, Cyclin E1 and Caspase 3 protein were determined by Western blot., Results: AICAR inhibited the proliferation of K562 cells in dose-dependent manner, and their IC50 value was 0.45 mmol/L at 48 hours. AICAR could induce arrest of K562 cells in G1 phase and down-regulated the protein expression levels of Cyclin D1 and Cyclin E1; whereas it didn't influence the cell apoptosis. Additionally, the growth inhibition of cells induced by IM was enhanced by AICAR., Conclusion: AICAR can inhibit the proliferation of K562 cells by arresting the cell cycle and enhancing the sensitivity of K562 cells to IM.

Parasitic worms (helminth) or their derivates can inhibit allergy and autoimmune diseases by inducing the activation of immune cells and thus the release of regulatory factors. A large number of animal experiments have shown that adoptive transfer of lymphocytes can protect against immune deregulation and have potential clinical applications. In this review, we discuss the research progress on the role of adoptive transfer of immune cells in worm-induced regulation of allergy and autoimmune diseases.

Objective: This study was purposed to investigate the effect of YM155, a survivin inhibitor, on the apoptosis and autophagy of K562 cells., Methods: K562 cells were treated with YM155 at different concentration. Cell survival was analyzed by CCK-8 assay, the cell apoptosis was detected by flow cytometry. Survivin, BCL-2 and beclin1 mRNA expressions were determined by RT-PCR. Survivin, BCL-2, caspase-3, PARP and LC-3 protein expressions were assayed by Western blot., Results: YM155 inhibited the proliferation of K562 cells in a time- and dose-dependent manners. With the increasing of YM155 concentration and prolonging of action time, the expression levels of mRNA and protein of survivin and BCL-2 decreased, while the expression levels of caspase-3, PARP, beclin1 and LC-3 increased. Compared with the YM155 group, the protein levels of LC-3 and caspase-3 were lower in YM155 combined with 3-MA group., Conclusion: YM155 can inhibit K562 cell proliferation by inducing apoptosis and autophagy, while autophagy induction effect can enhance its cytotoxic effect.