Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina.

Treatment with a tyrosine kinase inhibitor (TKI) targeting BCR-ABL1 is currently the standard of care for patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP). In this study, we present results of the ENESTchina (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-China) that was conducted to investigate nilotinib 300 mg twice daily vs imatinib 400 mg once daily in a Chinese population. ENESTchina met its primary end point with a statistically significant higher rate of major molecular response (MMR; BCR-ABL1 ≤0.

Effect of minichromosome maintenance protein 2 deficiency on the locations of DNA replication origins.

Minichromosome maintenance (MCM) proteins are loaded onto chromatin during G1-phase and define potential locations of DNA replication initiation. MCM protein deficiency results in genome instability and high rates of cancer in mouse models. Here we develop a method of nascent strand capture and release and show that MCM2 deficiency reduces DNA replication initiation in gene-rich regions of the genome.

Lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed or refractory multiple myeloma and renal impairment.

Lower starting doses of lenalidomide (LEN) are recommended for patients with renal impairment (RI). In the present study, we conducted a subgroup analysis of the MM-021 registration trial to investigate the efficacy and safety of LEN plus low-dose dexamethasone (LoDEX) in Chinese patients with advanced relapsed or refractory multiple myeloma (RRMM) based on levels of RI. Patients received LEN+LoDEX until disease progression or discontinuation.

Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia.

Purpose: This prospective phase II, open label, study was designed to assess the efficacy and safety of D-CAG induction treatment for elderly patients with newly diagnosed AML.

Experimental Design: All patients in this study were treated with decitabine of 15 mg/m2 for 5 days and G-CSF for priming, in combination with cytarabine of 10-mg/m2 q12h for 7 days and aclarubicin of 10 mg/day for 4 days (D-CAG).

Results: Among 85 evaluable patients, overall response rate (ORR) and complete remission (CR) were 82.

The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.

Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.

[Acute promyelocytic leukaemia with translocations of t(15;17)(q22;q21) and rob(13;21): a case report and literatures review].

Objective: To report an acute promyelocytic leukaemia (APL) case with translocation of rob (13;21) t(15;17) (q22;q21) and review its clinical and laboratory characteristics.

Methods: Based on routine karyotype analysis and bone marrow morphology, we further used double color double fluorescent in situ hybridization (DCDF-FISH) and reverse transcriptase PCR (RT-PCR) to examine the patient's abnormities on cytogenetic and molecular biology, and reveal the clinical characteristics of this rare translocation also from the related literatures.

Results: The clinical manifestation and bone marrow morphology examination of this patient were in accordance with pathologic feature of APL.

Pneumococcal wall teichoic acid is required for the pathogenesis of Streptococcus pneumoniae in murine models.

Pneumococcal asymptomatic colonization of the respiratory tracts is a major risk for invasive pneumococcal disease. We have previously shown that pneumococcal wall teichoic acid (WTA) was involved in pneumococcal infection of sepsis and adherence to epithelial and endothelial cells. In this study, we investigated the contribution of pneumococcal WTA to bacterial colonization and dissemination in murine models.

Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer.

Progression of aggressive prostate cancers (PCa) with androgen receptor splice variants or neuroendrocrine features is currently untreatable in the clinic. Therefore novel therapies are urgently required. We conducted RNA-seq using tumors from a unique murine transplant mouse model which spontaneously progresses to metastatic disease.

Characterization of TAZ domains important for the induction of breast cancer stem cell properties and tumorigenesis.

The Hippo pathway is an evolutionarily conserved regulator of tissue growth and cell fate during development and regeneration. Conversely, deregulation of the Hippo pathway has been reported in several malignancies. Here, we used integrative functional genomics approaches to identify TAZ, a transcription co-activator and key downstream effector of the Hippo pathway, as an essential driver for the propagation of TNBC malignant phenotype.

Copy number variation analysis based on AluScan sequences.

Background: AluScan combines inter-Alu PCR using multiple Alu-based primers with opposite orientations and next-generation sequencing to capture a huge number of Alu-proximal genomic sequences for investigation. Its requirement of only sub-microgram quantities of DNA facilitates the examination of large numbers of samples. However, the special features of AluScan data rendered difficult the calling of copy number variation (CNV) directly using the calling algorithms designed for whole genome sequencing (WGS) or exome sequencing.

Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS2 score ⩾ 2.

Background: The nonvitamin K antagonist oral anticoagulants pivotal clinical trials for stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient characteristics.

Objective: We sought to evaluate the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants in the management of stroke prevention in atrial fibrillation by adjusting for differences in baseline stroke risk and the length of follow-up among the four phase 3 randomized controlled trials.

Methods: We conducted a systematic literature review of randomized controlled trials evaluating the nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation and performed a network meta-analysis using data from ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and ARISTOTLE, with warfarin as a common comparator.

Isolation and sequencing of active origins of DNA replication by nascent strand capture and release (NSCR).

Nascent strand capture and release (NSCR) is a method for isolation of short nascent strands to identify origins of DNA replication. The protocol provided involves isolation of total DNA, denaturation, size fractionation on a sucrose gradient, 5'-biotinylation of the appropriate size nucleic acids, binding to a streptavidin coated magnetic beads, intensive washing, and specific release of only the RNA-containing chimeric nascent strand DNA using ribonuclease I (RNase I). The method has been applied to mammalian cells derived from proliferative tissues and cell culture but could be used for any system where DNA replication is primed by a small RNA resulting in chimeric RNA-DNA molecules.

[A comparable analysis of IPSS and IPSS-R for evaluating prognosis of myelodysplastic syndrome].

Objective: To investigate the patients' characteristics and efficacy of prognosis evaluation by International Prognosis Scoring System (IPSS) and Revised International Prognosis Scoring System (IPSS-R) in patients with myelodysplastic syndrome (MDS).

Methods: Prognostic value of IPSS and IPSS-R was evaluated on clinical data from 159 MDS patients, according to WHO classification.

Results: With a median age of 44 years (range:15-80 years), MDS patients had the frequency of 38.

[1:2 matched case-control study on the risk factors related to congenital heart disease during the peri-conceptional period].

Objective: To explore the possible risk factors during the periconceptional period relevant on the occurrence of congenital heart diseases (CHD) in the offspring.

Methods: A 1:2 matched case-control study was designed. From January 2012 to January 2014 in a district from Wuhan city, HuBei province, children were proved by MCH institutions through the "free screening for congenital heart disease" program.

Head circumference growth reference charts of children younger than 7 years in Chinese rural areas.

Background: The head circumference growth reference charts for children in China are presently based on urban children. However, the references may not apply to rural children because of the differences between urban and rural areas, such as economy, culture, and dietary habits. Our objective was to provide a reliable continuous set of head circumference growth reference charts for male and female children less than 7 years of age in Chinese rural areas.

Randomized controlled trials in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis.

This systematic literature review with meta-analysis was conducted on the clinical efficacy and safety of interventions used in the treatment of chronic lymphocytic leukemia (CLL). We systematically searched databases (PubMed, Cochrane Library, and Embase; 1997 to August 2, 2012), conference abstracts, bibliographic reference lists, recent reviews, and Clinicaltrials.gov.

KGFR promotes Na+ channel expression in a rat acute lung injury model.

Background: Binding of keratinocyte growth factor (KGF) to the KGF receptor (KGFR) plays an important role in the recovery of alveolar epithelial cells from acute lung injury (ALI).

Objectives: To evaluate the effect of gene therapy via adenovirus gene transfer of KGFR on the treatment of ALI.

Methods: Sprague-Dawley rats were divided into four groups: normal controls, injury controls, normal adenovirus transduced group and injury adenovirus transduced group.

Coxsackievirus B3 engineered to contain microRNA targets for muscle-specific microRNAs displays attenuated cardiotropic virulence in mice.

Unlabelled: Coxsackievirus B3 (CVB3) is trophic for cardiac tissue and is a major causative agent for viral myocarditis, where local viral replication in the heart may lead to heart failure or even death. Recent studies show that inserting microRNA target sequences into the genomes of certain viruses can eradicate these viruses within local host tissues that specifically express the cognate microRNA. Here, we demonstrated both in vitro and in vivo that incorporating target sequences for miRNA-133 and -206 into the 5' untranslated region of the CVB3 genome ameliorated CVB3 virulence in skeletal muscle and myocardial cells that specifically expressed the cognate cellular microRNAs.

[Comparative study on the efficacy of Hyper CVAD/MA regimen and CHOP or CHOP like regimen in the treatment of primary peripheral T cell lymphoma].

Objective: To evaluate the curative efficacy and safety of two regimens, Hyper CVAD/MA and CHOP/CHOP, in the treatment of primary peripheral T cell lymphoma (PTCL).

Methods: The clinical data of 80 primary PTCL patients were retrospectively analyzed, and the efficacy and safety of the two regimens, Hyper CVAD/MA and CHOP/CHOP, were evaluated.

Results: Of 80 patients with primary PTCL, 23 were treated with Hyper CVAD/MA regimen (HM group, experimental group) and 57 with CHOP or CHOP-like regimen (CC group, control group).

Mucosal immunization with the live attenuated vaccine SPY1 induces humoral and Th2-Th17-regulatory T cell cellular immunity and protects against pneumococcal infection.

Mucosal immunization with attenuated vaccine can protect against pneumococcal invasion infection, but the mechanism was unknown. Our study found that mucosal delivery with the live attenuated SPY1 vaccine strain can confer T cell- and B cell-dependent protection against pneumococcal colonization and invasive infection; yet it is still unclear which cell subsets contribute to the protection, and their roles in pneumococcal colonization and invasion remain elusive. Adoptive transfer of anti-SPY1 antibody conferred protection to naive μMT mice, and immune T cells were indispensable to protection examined in nude mice.

Mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: a systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I-IIIA non-small cell lung cancer (NSCLC) patients.

Methods: A systematic search of published literature was conducted using the main databases (MEDLINE, PubMed, EMBASE, and Cochrane databases) to identify relevant randomized controlled trials that compared MLND vs. MLNS in NSCLC patients.

Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China.

This stud y examined the epidemiology, risk factors, management, and outcome of invasive fungal infection (IFI) in patients receiving chemotherapy for hematological malignancy in China. IFI risk factors were analyzed using univariate analysis and multivariate logistic regression. In total, 4,192 patients receiving 4,889 chemotherapy courses were enrolled [mean age 40.

Inducible Costimulator Gene-Transduced Bone Marrow-Derived Mesenchymal Stem Cells Attenuate the Severity of Acute Graft-Versus-Host Disease in Mouse Models.

In murine allogeneic transplantation models, ICOS gene-transduced bone marrow-derived mesenchymal stem cells (MSCs(ICOS-EGFP)) were evaluated for their effects on GvHD severity and long-term survival. Lethally irradiated BALB/c or first filial generation of BALB/c and C57BL/6 (CB6F1) mice were transplanted with bone marrow cells and splenocytes from C57BL/6 mice to establish acute GvHD models. Recipient mice were injected with MSCs(ICOS-EGFP), MSCs, MSCs(EGFP), ICOS-Ig fusion protein, MSCs + ICOS-Ig, or PBS (control group).

A simple model clarifies the complicated relationships of complex networks.

Real-world networks such as the Internet and WWW have many common traits. Until now, hundreds of models were proposed to characterize these traits for understanding the networks. Because different models used very different mechanisms, it is widely believed that these traits origin from different causes.