Objective To investigate the frequency of NPM1 mutation and its clinical significance in patients with cytogenetically normal acute myeloid leukemia (CN-AML). Methods The data of 190 patients with CN-AML were collected from Department of Hematology, Tongji Hospital between January 2008 and June 2015, and the discrepancies in clinical features and efficacy between CN-AML patients with NPM1 mutation and those without NPM1 mutation were also analyzed. Results Among the 190 CN-AML patients, NPM1 mutation was found in 44 patients (23.16 %). The proportion of bone marrow blast cells and the count of peripheral white blood cells in patients with NPM1 mutation were higher than those in patients without NPM1 mutation (75.82 % vs. 63.87 % , P <0.05; 75.7 ×109/L vs. 60.0 ×109/L, P <0.05). The rate of response (complete remission + partial remission) in patients with NPM1 mutation was also higher than that in patients without NPM1 mutation [70.09 %(22/31) vs. 56.91 %(45/79), P<0.05) ]. Conclusion NPM1 mutation is associated with higher tumor burden and higher remission rate in CN-AML patients.

Objective To analyze clinical and genetic risk factors of refractory or relapsed acute myeloid leukemia (AML) patients,and evaluate the efficacy of reinduction of chemotherapy.Methods 296 newly diagnosed AML patients,including 89 refractory or relapsed cases,were observed with clinical characteristics.And the efficiency of different reinduction chemotherapy regimens were compared.Results Compared with the non-refractory or relapsed AML,age,complex karyotype and Fms like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) gene mutations were risk factors of relapsed or refractory AML (P ＜ 0.05).Seventy-eight refractory and relapsed AML patients received reinduction therapy.The overall response rate (the complete response rate and the partial response rate) was 44.90 ％ (30/78).All reinduction regimens were divided into three categories:using the initial induction scheme or using new induction scheme including some chemotherapeutics without cross-resistance (regimen A),using the induction regimen containing medium-or high-dose cytarabine (regimen B),and using priming regimen containing of G-CSF,cytarabine,aclacinomycin or homoharringtonine (regimen C).Their overall response rate were 35.12 ％ (13/37),61.90 ％ (13/21) and 45.00 ％ (9/20),respectively,in which the overall response rate of regimen B was statistically higher than regimen A (P ＜ 0.05).Conclusions Age,complex karyotype and FLT3-ITD mutation were important causes of relapsed or refractory AML.The overall response rates were different among three different reinduction regimens.It is helpful to improve the overall response rate of reinduction therapy to use the regimen containing medium-or high-dose cytarabine,which was more suitable for young patients.For patients with poor tolerance,the priming regimen suit was more helpful to improve the overall response rate.

Abstract: To develop novel live attenuated influenza vaccine, we explored the feasibility to attenuate influenza virus by codon deoptimization of NS1. According to the codon usage bias in influenza A virus, we designed and synthesized a condon-deoptimized NS gene by substituting codons of 110 amino acids in the NS1 gene of A/Puerto Rico/8/34(H1N1) with unpreferred synonymous codons. The influenza A virus with the codon deoptimized NS1 gene (deoNS virus) was rescued by reverse genetics. Plaque forming assay and virus growth curve showed that the growth of deoNS virus was reduced about 1000 times in MDCK cells compared to that of the wild-type virus. Intranasal inoculation with deoNS virus did not cause death or evident disease in infected BALB/c mice. Furthermore, the virus titer in the lungs of mice infected with deoNS virus was significantly lower (i.e. 100-1000 times) than that of wild-type virus. Our results indicated that influenza virus could be effectively attenuated by synonymous codon deoptimization of NS1 gene. This strategy will be useful to develop new attenuated candidates for the production of live attenuated influenza vaccines.
Animals ; Base Sequence ; Chick Embryo ; Codon ; genetics ; Influenza A virus ; genetics ; pathogenicity ; Influenza Vaccines ; immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Orthomyxoviridae Infections ; immunology ; prevention & control ; Recombination, Genetic ; Vaccines, Attenuated ; immunology ; Viral Nonstructural Proteins ; genetics ; Virulence ; genetics

Objective To investigate the value of real-time virtual navigation system (RVS) combined with CEUS in guiding radiofrequency ablation (RFA) therapy of neonatal or recurrent lesions of hepatocellular carcinoma (HCC).Methods Totally 111 patients with neonatal or recurrent lesions of HCC after RFA therapy were enrolled.Seventy-eight patients with 86 lesions (77 neonatal lesions and 9 recurrent lesions) underwent RFA guided by RVS combined with CEUS (RVS combined with CEUS group),and 33 patients with 38 lesions (26 neonatal lesions and 12 recurrent lesions) underwent RFA guided by CEUS alone (control group).The precise localization,inactivation rate and local recurrence rate between the two groups were compared.Results Eighty-four lesions (84/86,97.67％) in RVS combined with CEUS group and 25 lesions (25/38,65.79％) in control group were clearly showed and localized (P＜0.001).One month after RFA therapy,the tumor inactivation rate in RVS combined with CEUS group and control group was 95.35 ％ (82/86) and 76.31％ (29/38),respectively (P=0.003).The local recurrence rate in RVS combined with CEUS group was 8.14％ (7/86),while was 36.84％ (14/38) in control group (x2 =15.434,P＜0.001).Conclusion RVS combined with CEUS guidance can improve the accurate position rate and early inactivation rate of RFA therapy for neonatal or recurrent lesions of HCC.

Objective To investigate the value of ultrasonic two‐dimensional speckle tracking imaging ( 2D‐ST I) layer‐specific strain and transmural gradient in evaluating the changes of hypertensive patients′left ventricular three layers myocardial function . Methods Thirty‐five hypertensive patients without renal insufficiency were selected as group A ,and 25 hypertensive patients with renal insufficiency as group B .For comparison ,40 healthy volunteers were gathered as control group . T hen ,the systolic peak longitudinal strain of the left ventricle( LPS) ,endocardium( LPS Endo ) ,mid‐cardium ( LPSMid ) and epicardium ( LPSEpi ) were collected .After that ,features of transmural gradient ( ΔLS ) and its percentage ( ΔLS% ) were analyzed . Results For each group ,gradient features exist in each layer of left ventricular myocardium :LPS Endo ＞LPSMid＞LPSEpi . For each group ,the differences between LPSEndo and LPSMid ,and that between LPSEndo and LPSEpi were both statistically significant( P ＜0 .05) . When it came to the differences between LPS Mid and LPSEpi ,those of group A and control group were both statistically significant ( P ＜0 .05 ) . Compared with control group ,the LPSEndo of group A ,and LPSEndo ,LPSMid and LPSEpi of group B declined ,all the differences were statistically significant ( P ＜0 .05 ) . Compared with group A ,LPS Endo ,LPSMid and LPSEpi of group B declined ,the differences were statistically significant ( all P ＜0 .05) . For ΔLS′s differences among all three groups ,there was no statistical significance( P ＞0 .05) . Compared with control group ,the ΔLS% Endo‐Mid of group A rised , and the ΔLS% Endo‐Mid , ΔLS% Mid‐Epi of group B rised , the differences were statistically siginificant ( all P ＜ 0 .05 ) . Compared with group A ,the ΔLS% Endo‐Mid ,ΔLS% Mid‐Epi of group B rised ,the differences were statistically siginificant( all P ＜0 .05) . Conclusions T he layer‐specific strain technique can quantitatively evaluate the changes of systolic function of the left ventricular myocardium in hypertensive patients . ΔLS% may have better sensitivity than ΔLS in dection of systolic function damage of the left ventricular myocardium and can provide more reference for the evaluation of left ventricular systolic function .

Polygona-polysaccharose is an important indicator to measure the quality of Polygonati Rhizoma. The polygona-polysaccharose has the effect of lowering blood sugar, regulating blood lipid, anti-fatigue, improving learning and memory ability. The Polygonati Rhizoma, as a Chinese herbal medicine with homology of medicine and food, has a good prospect and application value in the development of food and health products.

OBJECTIVE：To estab lish the fingerprint ，analyze the monosaccharide composition and content ，investigate the inhibitory effects of the polysaccharide from Desmodium styracifolium on α-glucosidase in vitro . METHODS ：Polysaccharide from D. styracifolium was prepared by water extraction and ethanol precipitation. After hydrolyzed by TFA and derived by PMP ，HPLC method was adopted to establish the fingerprint （using glucose peak as reference ），and analyze the constituent and content of monosaccharide. The content determination was performed on Phenomenex Luna C 18 column with mobile phase consisted of acetonitrile-0.05 mol/L potassium phosphate （pH adjusted to 6.8 with sodium hydroxide ）in gradient elution at the flow rate of 0.8 mL/min. The detection wavelength was set at 250 nm，and column temperature was set at 30 ℃. The sample size was 10 μL. Using acarbose as control ，PNPG assay was used to investigate the α-glucosidase inhibitory activity of polysaccharide from D. styracifolium. RESULTS ：There were 9 common peaks in HPLC fingerprints of 18 batches of samples ，and the similarity of 15 batches of samples was higher than 0.90. Totally 7 peaks were identified as mannose ，rhamnose，galacturonic acid ，glucose， galactose，xylose and arabinose. The contents of rhamnose ，galacturonic acid ，glucose，galactose and arabinose were 0.471-2.092， 1.379-8.919，2.560-35.679，1.194-6.905，0.566-4.158 mg/g，respectively. Based on rhamnose ，the molar ratios of the other four monosaccharides were 1.58-4.07，2.26-19.95，2.20-4.21 and 1.31-2.86，respectively. The inhibitory activity of polysaccharide from D. styracifolium on α-glucosidase increased with the increase of dose ，and the half inhibitory concentrations of it was 0.70 mg/mL， lower than 7.76 mg/mL of acarbose （positive control ）. CONCLUSIONS ：Glucose is the main component of D. styracifolium polysaccharide in different batches ，and the contents of monosaccharides are different. The polysaccharide from D. styracifolium have significant inhibitory activity on α-glucosidase，which is better than that of acarbose.

OBJECTIVETo summarize the clinical characteristics of peripheral blood, immune phenotypes, fusion genes and cytogenetics of patients with t(8;21) acute myeloid leukemia(AML) through the retrospective analysis of 586 patients with t(8;21) AML from 15 blood disease research centers in Northern area of China.

METHODSThe factors affecting prognosis of patients with t(8;21) AML were investigated by using univariate and multivariate COX regression.

RESULTSThe immune type of t(8;21) AML patients was mainly with HLA-DR, CD117, CD34, MPO, CD38, CD13and CD33(>95%), part of them with CD19and CD56; the most common accompanied mutation of t(8;21) AML patients was C-KIT mutation (37.8%); in addition to t(8;21) ectopic, the most common chromosomal abnormality was sex chromosome deletions (38.9%). The univariate analysis revealed a significant survival superiority of OS and PFS in t(8;21) AML patients of WBC≤3.5×10/L without C-KIT mutation, the newly diagnosed ones achieved HSCT(P<0.05), only survival superiority on OS in t(8;21) AML patients with extramedullary infiltration and CD19 positive; the results of multivariate analysis showed a significant survival superiority on OS and PFS in t(8;21) AML patients with WBC≤3.5×10/L(P<0.05).

CONCLUSIONThe clinical features of t(8;21) AML patients in China are similar to those in other countries, WBC≤3.5×10/L is a good prognostic factor while the C-KIT mutation is a poor one in t(8;21) AML patients.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.