Publications by authors named "Meiling Zhao"

30 Publications

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Natural population re-sequencing detects the genetic basis of local adaptation to low temperature in a woody plant.

Plant Mol Biol 2021 Mar 2. Epub 2021 Mar 2.

Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing, 100093, China.

Key Message: Total of 14 SNPs associated with overwintering-related traits and 75 selective regions were detected. Important candidate genes were identified and a possible network of cold-stress responses in woody plants was proposed. Local adaptation to low temperature is essential for woody plants to against changeable climate and safely survive the winter. To uncover the specific molecular mechanism of low temperature adaptation in woody plants, we sequenced 134 core individuals selected from 494 paper mulberry (Broussonetia papyrifera), which naturally distributed in different climate zones and latitudes. The population structure analysis, PCA analysis and neighbor-joining tree analysis indicated that the individuals were classified into three clusters, which showed forceful geographic distribution patterns because of the adaptation to local climate. Using two overwintering phenotypic data collected at high latitudes of 40°N and one bioclimatic variable, genome-phenotype and genome-environment associations, and genome-wide scans were performed. We detected 75 selective regions which possibly undergone temperature selection and identified 14 trait-associated SNPs that corresponded to 16 candidate genes (including LRR-RLK, PP2A, BCS1, etc.). Meanwhile, low temperature adaptation was also supported by other three trait-associated SNPs which exhibiting significant differences in overwintering traits between alleles within three geographic groups. To sum up, a possible network of cold signal perception and responses in woody plants were proposed, including important genes that have been confirmed in previous studies while others could be key potential candidates of woody plants. Overall, our results highlighted the specific and complex molecular mechanism of low temperature adaptation and overwintering of woody plants.
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http://dx.doi.org/10.1007/s11103-020-01111-xDOI Listing
March 2021

Causal role for sleep-dependent reactivation of learning-activated sensory ensembles for fear memory consolidation.

Nat Commun 2021 02 22;12(1):1200. Epub 2021 Feb 22.

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.

Learning-activated engram neurons play a critical role in memory recall. An untested hypothesis is that these same neurons play an instructive role in offline memory consolidation. Here we show that a visually-cued fear memory is consolidated during post-conditioning sleep in mice. We then use TRAP (targeted recombination in active populations) to genetically label or optogenetically manipulate primary visual cortex (V1) neurons responsive to the visual cue. Following fear conditioning, mice respond to activation of this visual engram population in a manner similar to visual presentation of fear cues. Cue-responsive neurons are selectively reactivated in V1 during post-conditioning sleep. Mimicking visual engram reactivation optogenetically leads to increased representation of the visual cue in V1. Optogenetic inhibition of the engram population during post-conditioning sleep disrupts consolidation of fear memory. We conclude that selective sleep-associated reactivation of learning-activated sensory populations serves as a necessary instructive mechanism for memory consolidation.
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http://dx.doi.org/10.1038/s41467-021-21471-2DOI Listing
February 2021

Oncogenic N-Ras mitigates oxidative stress-induced apoptosis of hematopoietic stem cells.

Cancer Res 2021 Jan 13. Epub 2021 Jan 13.

Medicine, University of Michigan–Ann Arbor

Leukemic relapse is believed to be driven by transformed hematopoietic stem cells that harbor oncogenic mutations or have lost tumor suppressor function. Recent comprehensive sequencing studies have shown that mutations predicted to activate Ras signaling are highly prevalent in hematologic malignancies and, notably, in refractory and relapsed cases. To better understand what drives this clinical phenomenon, we expressed oncogenic NrasG12D within the hematopoietic system in mice and interrogated its effects on hematopoietic stem cell (HSC) survival. N-RasG12D conferred a survival benefit to HSC and progenitors following metabolic and genotoxic stress. This effect was limited to HSC and early progenitors and was independent of autophagy and cell proliferation. N-RasG12D-mediated HSC survival was not affected by inhibition of the canonical Ras effectors such as MEK and PI3K. However, inhibition of the non-canonical Ras effector pathway protein kinase C (PKC) ameliorated the protective effects of N-RasG12D. Mechanistically, N-RasG12D lowered levels of reactive oxygen species (ROS), which correlated with reduced mitochondrial membrane potential and ATP levels. Inhibition of PKC restored the levels of ROS to that of control HSC and abrogated the protective effects granted by N-RasG12D. Thus, N-RasG12D activation within HSC promote cell survival through the mitigation of ROS, and targeting this mechanism may represent a viable strategy to induce apoptosis during malignant transformation of HSC.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-0118DOI Listing
January 2021

Effects of reduced platelet count on the prognosis for patients with non-small cell lung cancer treated with EGFR-TKI: a retrospective study.

BMC Cancer 2020 Nov 26;20(1):1152. Epub 2020 Nov 26.

Department of Geriatric Respiratory and Critical Care, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China.

Background: Progressive lung cancer is associated with abnormal coagulation. Platelets play a vital part in evading immune surveillance and angiogenesis in the case of tumor metastasis. The study aimed to analyze the predictive and prognostic effects of platelet count on non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).

Methods: This study retrospectively analyzed the prognostic effects of platelets on 52 NSCLC patients with epidermal growth factor receptor (EGFR) mutant following EGFR-TKI treatment. Related data, together with the progression-free survival (PFS) and overall survival (OS) were collected before and after 2 cycles of treatments (60 days).

Results: The anti-EGFR treatment markedly reduced the platelet count in 33 (63.5%) patients after 2 cycles of treatment. Multivariate Cox analysis revealed that, the decreased platelet count was closely correlated with the longer OS (HR = 0.293; 95%CI: 0.107-0.799; p = 0.017). Besides, the median OS was 326 days in the decreased platelet count group and 241 days in the increased platelet count group (HR = 0.311; 95%CI: 0.118-0.818; P = 0.018), as obtained from the independent baseline platelet levels and other clinical features.

Conclusions: The platelet count may predict the prognosis for EGFR-TKI treatment without additional costs. Besides, changes in platelet count may serve as a meaningful parameter to establish the prognostic model for NSCLC patients receiving anti-EGFR targeted therapy.
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http://dx.doi.org/10.1186/s12885-020-07650-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690006PMC
November 2020

ER-associated degradation preserves hematopoietic stem cell quiescence and self-renewal by restricting mTOR activity.

Blood 2020 Dec;136(26):2975-2986

Department of Internal Medicine.

Hematopoietic stem cells (HSC) self-renew to sustain stem cell pools and differentiate to generate all types of blood cells. HSCs remain in quiescence to sustain their long-term self-renewal potential. It remains unclear whether protein quality control is required for stem cells in quiescence when RNA content, protein synthesis, and metabolic activities are profoundly reduced. Here, we report that protein quality control via endoplasmic reticulum-associated degradation (ERAD) governs the function of quiescent HSCs. The Sel1L/Hrd1 ERAD genes are enriched in the quiescent and inactive HSCs, and conditional knockout of Sel1L in hematopoietic tissues drives HSCs to hyperproliferation, which leads to complete loss of HSC self-renewal and HSC depletion. Mechanistically, ERAD deficiency via Sel1L knockout leads to activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, we identify Ras homolog enriched in brain (Rheb), an activator of mTOR, as a novel protein substrate of Sel1L/Hrd1 ERAD, which accumulates upon Sel1L deletion and HSC activation. Importantly, inhibition of mTOR, or Rheb, rescues HSC defects in Sel1L knockout mice. Protein quality control via ERAD is, therefore, a critical checkpoint that governs HSC quiescence and self-renewal by Rheb-mediated restriction of mTOR activity.
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http://dx.doi.org/10.1182/blood.2020007975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770563PMC
December 2020

Genome-Wide Identification of the Gene Family in and Functional Analysis of , and in Shoot Branching.

Plants (Basel) 2020 Oct 1;9(10). Epub 2020 Oct 1.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.

The plant-specific TCP family proteins play an important role in the processes of plant growth and development. is a versatile perennial deciduous tree, and its genome data have been published. However, no comprehensive analysis of the gene family in has been undertaken. In this study, 20 genes () were identified in the genome. Phylogenetic analysis divided into three subclades, the PCF subclade, the CIN subclade and the CYC/TB1 subclade. Gene structure analysis displayed that all except contained one coding region. Conserved motif analysis showed that BpTCP proteins in the same subclade possessed similar motif structures. Segmental duplication was the primary driving force for the expansion of . Expression patterns showed that may play diverse biological functions in organ or tissue development. Transcriptional activation activity analysis of BpTCP8, BpTCP14 and BpTCP19 showed that they possessed transcriptional activation ability. The ectopic expression analysis in wild-type and ortholog mutant showed that , and could prevent rosette branch outgrowth. Collectively, our study not only established the first genome-wide analysis of the gene family, but also provided valuable information for understanding the function of in shoot branching.
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http://dx.doi.org/10.3390/plants9101301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650637PMC
October 2020

Cooperation between and Its Symbiotic Fungal Community To Improve Local Adaptation of the Host.

Appl Environ Microbiol 2020 09 1;86(18). Epub 2020 Sep 1.

Key Laboratory of Plant Resources, Institute of Botany, Chinese Academy of Sciences, Beijing, China

The genetic basis of plant local adaptation has been extensively studied, yet the interplay between local adaptation, plant genetic divergence, and the microbial community remains unclear. Our study used the restriction-site associated DNA sequencing (RAD-seq) approach to explore genetic divergence in and used internal transcribed spacers (ITS) to characterize fungal community. RAD-seq results show that individuals could be divided into three genotypes; this genotyping result was consistent with the classification of climate type at the sample site. Most of the 101 highly differentiated genes were related to stress resistance and the microbiome. Moreover, β-diversity results indicated that genetic divergence had a significant effect on fungal community across all compartments (0.01). At genus and operational taxonomic unit (OTU) level, , , OTU81578 (), and OTU1665209 () were found to be the major OTUs that contribute to differences in fungal community. The properties of cooccurrence networks vary greatly among three genotypes. The results of redundancy analysis (RDA) indicated that -associated fungal community was significantly related to its local adaptability. Our findings suggest that genetic divergence of is closely related to local adaptation, with significant effects on the associated fungal community, which in turn would enhance host local adaptability. This improves present understanding about the coevolution of microbial communities and the host plant. The coevolution of plants with the associated fungal community and its effect on plant adaptability are not clear, especially for native trees. This study focuses on the genetic basis of local adaptation in plants and the effect of genetic divergence of on the associated fungal community. We identified genes related to the microbiome that are important for local adaptation of the host. Our results show that genetic divergence in significantly affects the fungal community, which has a close connection with local adaptation. This helps us to understand the relationship between local adaptation, genetic divergence, and associated fungal communities. This study highlights the effect of plant genetic divergence on associated fungal community for native trees and establishes a close connection between this effect and local adaptability in the host. In addition, these observations lay a foundation for the research of coevolution of plants and their symbiotic microbiome through genome-wide association study (GWAS).
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http://dx.doi.org/10.1128/AEM.00464-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480386PMC
September 2020

Characteristics of Different Types of Basic Oxygen Furnace Slag Filler and its Influence on Properties of Asphalt Mastic.

Materials (Basel) 2019 Dec 4;12(24). Epub 2019 Dec 4.

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan 430070, China.

The fillers of ordinary and pyrolytic basic oxygen furnace (BOF) slag were selected to investigate the properties of their asphalt mastic. XRF (X-Ray Fluorescence) was used to analyze chemical composition of fillers. Meanwhile, SEM (Scanning Electron Microscope) and AIMS (Aggregate Image Measurement System) were utilized to explore meso-morphology, angularity and sphericity. Penetration, softening point and viscosity of asphalt mastic were discussed, while the rheological properties of asphalt mastic were studied by means of DSR (dynamic shear rheometer) and BBR (bending beam rheometer) tests. The experimental results show that chemical composition of different types of BOF slag is similar. The grinding energy consumption of pyrolytic BOF slag is higher than that of limestone and ordinary BOF slag. It is not recommended that pyrolytic BOF slag filler is produced by grinding process. The micro-texture structure of ordinary BOF slag filler is more abundant and their angularity index is about 15% higher than that of limestone filler. The stiffness modulus and rutting factor of asphalt mastic with ordinary BOF slag filler is higher than that of limestone filler. Meanwhile the incorporation of BOF slag filler will further reduce the low-temperature flow performance of asphalt mastic. The effect of pyrolytic BOF slag filler on the performance of asphalt mastic is less than that of ordinary BOF slag. Ordinary BOF slag filler can effectively improve high temperature anti-rutting stability of asphalt mixture. Ordinary BOF slag has a useful application prospect as filler in asphalt mixture.
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http://dx.doi.org/10.3390/ma12244034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947196PMC
December 2019

Prevalence and association of medication nonadherence with major adverse cardiovascular events in patients with myocardial infarction.

Medicine (Baltimore) 2019 Nov;98(44):e17826

Intensive Care Unit, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong.

Current study was to evaluate the prevalence of guideline recommended medications adherence in myocardial infarction (MI) patients postpercutaneous coronary intervention (PCI) and the association of medication nonadherence and major adverse cardiovascular events (MACEs).MI patients who underwent PCI in the last 12 months were enrolled. Demographic and clinical characteristics were collected and guideline recommended medications were evaluated. Patients were divided into with and without MACEs groups.Compared to patients without MACEs, those with MACEs were older (54.8 ± 16.4 vs 51.1 ± 15.2 years), more likely to be smoker (40.2% vs 31.9%), have higher body mass index (BMI; 25.0 ± 6.1 vs 23.8 ± 5.7 kg/m), diabetes (47.5% vs 37.8%), ischemic stroke (34.4% vs 25.6%), and estimated lower glomerular filtration rate (85.4 ± 9.6 vs 92.6 ± 10.7 mL/minute/1.73 m). Patients with MACEs were also more likely to present with ST-elevation MI (STEMI; 54.1% vs 48.4%) and to undergo urgent PCI (62.3% vs 56.3%). Furthermore, patients with MACEs were less likely to adhere to dual antiplatelet therapy (77.9% vs 85.9%), renin-angiotensin system inhibitor (62.3% vs 69.7%), and beta-blocker (69.7% vs 72.8%) treatment. In unadjusted model, medication nonadherence was associated with 2-fold higher odds of MACEs. After adjustment for demographics, risk factors, comorbidities, and peri-PCI characteristics, medications nonadherence remained independently associated with MACEs, with odds ratio of 1.40 (95% confidence interval: 1.29-1.87).Medications adherence rate among MI patients post-PCI is suboptimal in China, which is independently associated with MACEs.
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http://dx.doi.org/10.1097/MD.0000000000017826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946490PMC
November 2019

Geometric Characteristics of BOF Slag Coarse Aggregate and its Influence on Asphalt Concrete.

Materials (Basel) 2019 Mar 4;12(5). Epub 2019 Mar 4.

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan 430070, China.

In order to examine the geometric characteristics of BOF (blast oxygen furnace) slag coarse aggregate, the aggregate image measurement system (AIMS) was used to analyze the sphericity, gradient angularity and micro texture. Both volumetric and mechanical properties were studied to evaluate the influence of geometric characteristics of BOF slag coarse aggregate on asphalt concrete. The experimental results show that the BOF slag coarse aggregate has the characteristics of high sphericity, good angular performance and rough surface texture. The geometric characteristics of BOF slag has obvious influence on the volume performance of asphalt concrete. the higher sphericity of BOF slag causes an increase of the air voids of asphalt mixture. BOF slag coarse aggregate can effectively improve the road performances of asphalt concrete. BOF slag's higher sphericity and angularity improve the moisture damage resistance and rutting resistance of asphalt concrete. Results indicate that better angularity can slightly enhance the moisture resistance property of asphalt concrete, but excessively high angularity of BOF slag coarse aggregates reduces the anti-rutting properties of asphalt mixture.
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http://dx.doi.org/10.3390/ma12050741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427252PMC
March 2019

A Chromosome-Scale Genome Assembly of Paper Mulberry (Broussonetia papyrifera) Provides New Insights into Its Forage and Papermaking Usage.

Mol Plant 2019 05 26;12(5):661-677. Epub 2019 Feb 26.

Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing 100093, China; ChuangGou Science & Technology Co. Ltd., Beijing 100049, China. Electronic address:

Paper mulberry (Broussonetia papyrifera) is a well-known woody tree historically used for Cai Lun papermaking, one of the four great inventions of ancient China. More recently, Paper mulberry has also been used as forage to address the shortage of feedstuff because of its digestible crude fiber and high protein contents. In this study, we obtained a chromosome-scale genome assembly for Paper mulberry using integrated approaches, including Illumina and PacBio sequencing platform as well as Hi-C, optical, and genetic maps. The assembled Paper mulberry genome consists of 386.83 Mb, which is close to the estimated size, and 99.25% (383.93 Mb) of the assembly was assigned to 13 pseudochromosomes. Comparative genomic analysis revealed the expansion and contraction in the flavonoid and lignin biosynthetic gene families, respectively, accounting for the enhanced flavonoid and decreased lignin biosynthesis in Paper mulberry. Moreover, the increased ratio of syringyl-lignin to guaiacyl-lignin in Paper mulberry underscores its suitability for use in medicine, forage, papermaking, and barkcloth making. We also identified the root-associated microbiota of Paper mulberry and found that Pseudomonas and Rhizobia were enriched in its roots and may provide the source of nitrogen for its stems and leaves via symbiotic nitrogen fixation. Collectively, these results suggest that Paper mulberry might have undergone adaptive evolution and recruited nitrogen-fixing microbes to promote growth by enhancing flavonoid production and altering lignin monomer composition. Our study provides significant insights into genetic basis of the usefulness of Paper mulberry in papermaking and barkcloth making, and as forage. These insights will facilitate further domestication and selection as well as industrial utilization of Paper mulberry worldwide.
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http://dx.doi.org/10.1016/j.molp.2019.01.021DOI Listing
May 2019

Adaptive endoplasmic reticulum stress signalling via IRE1α-XBP1 preserves self-renewal of haematopoietic and pre-leukaemic stem cells.

Nat Cell Biol 2019 03 18;21(3):328-337. Epub 2019 Feb 18.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.

Over their lifetime, long-term haematopoietic stem cells (HSC) are exposed to a variety of stress conditions that they must endure. Many stresses, such as infection/inflammation, reactive oxygen species, nutritional deprivation and hypoxia, activate unfolded protein response signalling, which induces either adaptive changes to resolve the stress or apoptosis to clear the damaged cell. Whether unfolded-protein-response signalling plays any role in HSC regulation remains to be established. Here, we report that the adaptive signalling of the unfolded protein response, IRE1α-XBP1, protects HSCs from endoplasmic reticulum stress-induced apoptosis. IRE1α knockout leads to reduced reconstitution of HSCs. Furthermore, we show that oncogenic N-Ras activates IRE1α-XBP1, through MEK-GSK3β, to promote HSC survival under endoplasmic reticulum stress. Inhibiting IRE1α-XBP1 abolished N-Ras-mediated survival under endoplasmic reticulum stress and diminished the competitive advantage of Nras HSCs in transplant recipients. Our studies illuminate how the adaptive endoplasmic reticulum stress response is advantageous in sustaining self-renewal of HSCs and promoting pre-leukaemic clonal dominance.
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http://dx.doi.org/10.1038/s41556-019-0285-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745703PMC
March 2019

WDR74 functions as a novel coactivator in TGF-β signaling.

J Genet Genomics 2018 12 27;45(12):639-650. Epub 2018 Nov 27.

MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China; Department of Molecular & Cellular Biology and Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:

Smads are critical intracellular signal transducers for transforming growth factor-β (TGF-β) in mammalian cells. In this study, we have identified WD repeat-containing protein 74 (WDR74) as a novel transcriptional coactivator for Smads in the canonical TGF-β signaling pathway. Through direct interactions with Smad proteins, WDR74 enhances TGF-β-mediated phosphorylation and nuclear accumulation of Smad2 and Smad3. Consequently, WDR74 enables stronger transcriptional responses and more robust TGF-β-induced physiological responses. Our findings have elucidated a critical role of WDR74 in regulating TGF-β signaling.
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http://dx.doi.org/10.1016/j.jgg.2018.08.005DOI Listing
December 2018

Oncogenic N-Ras and Tet2 haploinsufficiency collaborate to dysregulate hematopoietic stem and progenitor cells.

Blood Adv 2018 06;2(11):1259-1271

Department of Internal Medicine and.

Concurrent genetic lesions exist in a majority of patients with hematologic malignancies. Among these, somatic mutations that activate oncogenes and inactivate the epigenetic modifier ten-eleven translocation 2 () frequently co-occur in human chronic myelomonocytic leukemias (CMMLs) and acute myeloid leukemias, suggesting a cooperativity in malignant transformation. To test this, we applied a conditional murine model that endogenously expressed oncogenic and monoallelic loss of and explored the collaborative role specifically within hematopoietic stem and progenitor cells (HSPCs) at disease initiation. We demonstrate that the 2 mutations collaborated to accelerate a transplantable CMML-like disease in vivo, with an overall shortened survival and increased disease penetrance compared with single mutants. At preleukemic stage, N-Ras and Tet2 haploinsufficiency together induced balanced hematopoietic stem cell (HSC) proliferation and enhanced competitiveness. / HSCs displayed increased self-renewal in primary and secondary transplantations, with significantly higher reconstitution than single mutants. Strikingly, the 2 mutations together conferred long-term reconstitution and self-renewal potential to multipotent progenitors, a pool of cells that usually have limited self-renewal compared with HSCs. Moreover, HSPCs from / mice displayed increased cytokine sensitivity in response to thrombopoietin. Therefore, our studies establish a novel tractable CMML model and provide insights into how dysregulated signaling pathways and epigenetic modifiers collaborate to modulate HSPC function and promote leukemogenesis.
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http://dx.doi.org/10.1182/bloodadvances.2018017400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998937PMC
June 2018

Identification and Functional Divergence Analysis of WOX Gene Family in Paper Mulberry.

Int J Mol Sci 2017 Aug 16;18(8). Epub 2017 Aug 16.

Key Laboratory of Plant Resources, Institute of Botany, The Chinese Academy of Sciences, Beijing 100093, China.

The WOX (WUSCHEL-related homeobox) is a plant-specific transcription factor involved in plant development and stress response. However, few studies have been reported on the WOX gene in woody plants. In this study, 10 genes were isolated from paper mulberry by RACE-PCR and categorized into three clades through phylogenetic analysis, ancient, intermediate and WUS clade. Among them, five members had the transcriptional activity detected by yeast one-hybrid and seven were uniquely localized to the nucleus through green fluorescent protein (GFP) observation. The expression patterns of genes in different tissues and under diverse treatments were quantified by the qRT-PCR method. Results showed that was expressed in the apical bud, stem and root, and functioned only in the root tip, and three regulated leaf development redundantly. and were induced by indole-3-acetic acid (IAA) or jasmonic acid (JA), while was repressed by five phytohormones. Interestingly, most BpWOX genes were responsive to the abiotic stress stimuli of drought, salt, cold, and cadmium (CdCl₂). Together, our study revealed that BpWOXs were functionally divergent during paper mulberry development and environmental adaptation, which might be related to their evolutionary relationships. Our work will benefit the systematic understanding of the precise function of WOX in plant development and environmental stress responses.
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http://dx.doi.org/10.3390/ijms18081782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578171PMC
August 2017

[Effect of global end diastolic volume index guidance fluid resuscitation in elderly patients with septic shock].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017 Jun;29(6):486-490

Department of Critical Care Medicine, Zibo Central Hospital, Zibo 255036, Shandong, China. Corresponding author: Zhang Rumin, Email:

Objective: To evaluate the effect of global end diastolic volume index (GEDVI) on fluid resuscitation in elderly patients with septic shock.

Methods: A prospective randomized controlled trial (RCT) was conducted. Septic shock patients over 65 years admitted to intensive care unit (ICU) of Shandong Province, Zibo Central Hospital from January 2013 to December 2015 were enrolled. The patients were randomly divided into control group and observation group, 20 cases in each group. In accordance with the guidelines for the treatment of septic shock, early goal-directed therapy (EGDT), rehydration in the control group was treated with the guide of central venous pressure (CVP); observation group was received pulse indicator continuous cardiac output (PiCCO) monitoring, and rehydration was treated according to the GEDVI and extravascular lung water index (EVLWI), i.e. GEDVI was maintained in 650-800 mL/m, EVLWI was not obviously increased compared with the basic value and without the emphasis of CVP. Initial acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure score (SOFA), procalcitonin (PCT), mean arterial pressure (MAP), lactic acid (Lac) and oxygenation index (PaO/FiO); serial Lac, central venous to arterial carbon dioxide pressure (Pcv-aCO), fluid balance, the amount of noradrenaline accumulation, PaO/FiO after 6, 24 and 48 hours resuscitation; mechanical ventilation time, incidence of acute heart failure, ICU hospitalization time and 28-day mortality were recorded.

Results: There was no significant difference in gender, age, APACHE II score, SOFA score, primary disease, infection site and basal PCT, MAP, Lac, PaO/FiO between the two groups. Compared with the control group, 6 hours Lac, Pcv-aCO recovery, positive fluid balance, noradrenaline accumulation and PaO/FiO of the observation group showed no significant difference; positive fluid balance 24 hours in the recovery was significantly reduced (mL: 2 919.80±986.44 vs. 3 991.40±933.53), Pcv-aCO significantly decreased [mmHg (1 mmHg = 0.133 kPa): 5.55±1.43 vs. 7.10±2.38], PaO/FiO significantly improved (mmHg: 194.80±28.57 vs. 177.65±23.46), and noradrenaline accumulation was increased significantly (mg: 40.99±20.69 vs. 27.31±19.34) with statistically significant difference (all P < 0.05); the blood level of Lac 48 hours in the recovery was significantly decreased (mmol/L: 1.16±0.89 vs. 1.85±1.01), Pcv-aCO (mmHg: 5.35±1.18 vs. 6.70±2.34), and PaO/FiO (mmHg: 215.75±33.84 vs. 190.60±32.89) were further improved, the positive fluid balance was significantly reduced (mL: 3 141.55±1 245.69 vs. 4 533.85±1 416.67, all P < 0.05). Compared with the control group, mechanical ventilation time (days: 3.65±1.31 vs. 4.50±1.19), ICU hospitalization time (days: 5.80±1.67 vs. 7.15±2.30) was significantly shorter in the observation group (both P < 0.05), acute heart failure rate was decreased significantly (5.0% vs. 30.0%, P < 0.05), but the 28-day mortality showed no statistical significance (25.0% vs. 40.0%, P = 0.311).

Conclusions: Compared to the conventional EGDT methods, fluid resuscitation under the guidance of GEDVI in elderly patients with septic shock with less liquid loading, can achieve better oxygenation and reduce heart failure, shorten the duration of mechanical ventilation and ICU stay, and play an important significant guidance for elderly patients' fluid resuscitation with septic shock.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2017.06.002DOI Listing
June 2017

Function evaluation of asphalt mixture with industrially produced BOF slag aggregate.

J Appl Biomater Funct Mater 2016 Jul 4;14 Suppl 1:e7-e10. Epub 2016 Jul 4.

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan - China.

Background: Laboratory research suggested that basic oxygen furnace (BOF) slag-based asphalt mixture was a functional material. However, the BOF slag aggregate's quality was difficult to control when it was heavily used in entity engineering.

Aims: The primary objective of this research was to evaluate the functional performances of asphalt mixture containing BOF slag coarse aggregate (BSCA), which was from an industrialized production line.

Methods: Limestone mixture was a control group. The Marshall method was first adopted to design asphalt mixtures. The performances of limestone asphalt mixture and BOF slag asphalt mixture including fatigue failure resistance and moisture stability were then evaluated and compared.

Results: Results showed that the asphalt mixture containing BSCA possessed better durability, which meant the quality of BSCA from industrialized production lines was well controlled and this BSCA can be heavily used in entity engineering.
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http://dx.doi.org/10.5301/jabfm.5000297DOI Listing
July 2016

Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-β responses.

Oncogene 2017 01 6;36(3):362-372. Epub 2016 Jun 6.

Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang 310058, China.

Smad proteins are central mediators in the canonical transforming growth factor-β (TGF-β) signaling pathway in mammalian cells. We report here that bromodomain-containing protein 7 (BRD7) functions as a novel transcription coactivator for Smads in TGF-β signaling. BRD7 forms a TGF-β inducible complex with Smad3/4 through its N-terminal Smad-binding domain. BRD7 simultaneously binds to acetylated histones to promote Smad-chromatin association, and associates with histone acetyltransferase p300 to enhance Smad transcriptional activity. Ectopic expression of BRD7, but not its mutants defective in Smad binding, enhances TGF-β transcriptional, tumor-suppressing and epithelial-mesenchymal transition responses. Conversely, depletion of BRD7 inhibits TGF-β responses. Thus, our study provides compelling evidence for a new function of BRD7 in fine-tuning TGF-β physiological responses.
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http://dx.doi.org/10.1038/onc.2016.204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5140778PMC
January 2017

Surgical treatment for primary pulmonary lymphoepithelioma-like carcinoma.

Interact Cardiovasc Thorac Surg 2016 07 18;23(1):41-6. Epub 2016 Mar 18.

Southern Medical University, Guangzhou, China Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare but unique subtype of non-small-cell lung cancer (NSCLC). Our study aimed to evaluate clinicopathological characteristics and the value of surgical treatment for LELC and explore the relevant prognostic factors in a relatively large cohort.

Methods: We retrospectively reviewed the medical records of 39 lung LELC patients who underwent pulmonary resection with curative intent between January 2009 and December 2013. The clinical and pathological characteristics, survival data and relevant prognostic factors were analysed.

Results: The median age of lung LELC patients was 47 years (36-81), and 32 of 39 patients were non-smokers (82.1%). Positive expression of P63 and CK5/6 was shown in all the tested LELC specimens. In situ hybridization of Epstein-Bar virus-encoded RNA (EBER) was performed in 36 patients and all of them were positive. However, epidermal growth factor receptor (EGFR) mutational analysis was done in 19 patients and all of them were wild-type. The median follow-up time was 26.0 months in our cohort, and 6-, 12-, 24- and 36-month recurrence-free survival (RFS) rates were 92, 82, 73 and 73%, respectively. Patients with positive lymph nodes experienced significantly worse postoperative RFS than those with negative ones (P = 0.002). Multivariate survival analysis confirmed that only lymph node involvement [RR 0.051; 95% confidence interval, 0.003-0.991, P = 0.049] was an independent prognostic factor.

Conclusions: Primary lung LELC is closely associated with Epstein-Bar virus infection but not involved in EGFR mutation pathway. Radical surgery could achieve a good outcome for resectable pulmonary LELC, and regional lymph node status is a vital prognostic factor.
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http://dx.doi.org/10.1093/icvts/ivw064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986741PMC
July 2016

High-throughput deep screening and identification of four peripheral leucocyte microRNAs as novel potential combination biomarkers for preeclampsia.

J Perinatol 2016 Apr 17;36(4):263-7. Epub 2015 Dec 17.

The Second Hospital of Shanxi Medical University, TaiYuan, Shanxi Province, China.

Objective: To identify the specific microRNA (miRNA) biomarkers of preeclampsia (PE), the miRNA profiles analysis were performed.

Study Design: The blood samples were obtained from five PE patients and five normal healthy pregnant women. The small RNA profiles were analyzed to identify miRNA expression levels and find out miRNAs that may associate with PE. The quantitative reverse transcriptase-PCR (qRT-PCR) assay was used to validate differentially expressed peripheral leucocyte miRNAs in a new cohort.

Result: The data analysis showed that 10 peripheral leucocyte miRNAs were significantly differently expressed in severe PE patients. Four differently expressed miRNAs were successfully validated using qRT-PCR method.

Conclusion: We successfully constructed a model with high accuracy to predict PE. A combination of four peripheral leucocyte miRNAs has great potential to serve as diagnostic biomarkers of PE.
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http://dx.doi.org/10.1038/jp.2015.192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819758PMC
April 2016

The cold responsive mechanism of the paper mulberry: decreased photosynthesis capacity and increased starch accumulation.

BMC Genomics 2015 Nov 5;16:898. Epub 2015 Nov 5.

Key Laboratory of Plant Resources, Institute of Botany, the Chinese Academy of Sciences, Beijing, 100093, China.

Background: Most studies on the paper mulberry are mainly focused on the medicated and pharmacology, fiber quality, leaves feed development, little is known about its mechanism of adaptability to abiotic stress. Physiological measurement, transcriptomics and proteomic analysis were employed to understand its response to cold stress in this study.

Methods: The second to fourth fully expanded leaves from up to down were harvested at different stress time points forthe transmission electron microscope (TEM) observation. Physiological characteristics measurement included the relative electrolyte leakage (REL), SOD activity assay, soluble sugar content, and Chlorophyll fluorescence parameter measurement. For screening of differentially expressed genes, the expression level of every transcript in each sample was calculated by quantifying the number of Illumina reads. To identify the differentially expressed protein, leaves of plants under 0, 6, 12, 24, 48 and 72 h cold stress wereharvested for proteomic analysis. Finally, real time PCR was used to verify the DEG results of the RNA-seq and the proteomics data.

Results: Results showed that at the beginning of cold stress, respiratory metabolism was decreased and the transportation and hydrolysis of photosynthetic products was inhibited, leading to an accumulation of starch in the chloroplasts. Total of 5800 unigenes and 38 proteins were affected, including the repressed expression of photosynthesis and the enhanced expression in signal transduction, stress defense pathway as well as secondary metabolism. Although the transcriptional level of a large number of genes has been restored after 12 h, sustained cold stress brought more serious injury to the leaf cells, including the sharp rise of the relative electrolyte leakage, the declined Fv/Fm value, swelled chloroplast and the disintegrated membrane system.

Conclusion: The starch accumulation and the photoinhibition might be the main adaptive mechanism of the paper mulberry responded to cold stress. Most of important, enhancing the transport and hydrolysis of photosynthetic products could be the potential targets for improving the cold tolerance of the paper mulberry.
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http://dx.doi.org/10.1186/s12864-015-2047-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634900PMC
November 2015

Prognostic value of ERCC1 mRNA expression in non-small cell lung cancer, breast cancer, and gastric cancer in patients from Southern China.

Int J Clin Exp Pathol 2014 1;7(12):8312-21. Epub 2014 Dec 1.

Ningbo University School of Medicine Ningbo, China.

Background: Excision repair cross complementation group 1 (ERCC1) is a nucleotide excision repair pathway gene which provides protection against platinum-based chemotherapy-induced DNA damage.

Methods: ERCC1 mRNA expression was quantified by quantitative real-time reverse-transcription PCR in paraffin-embedded non-small cell lung cancer (NSCLC; n = 357), gastric cancer (n = 106), and breast cancer (n = 363) tissues. Survival curves were generated by Kaplan-Meier analysis; Cox proportional multivariate regression analysis was applied.

Results: ERCC1 mRNA expression was significantly higher in breast cancer than gastric cancer or NSCLC (both P < 0.0001), but not significantly different in NSCLC and gastric cancer (P = 0.119). In NSCLC, the low ERCC1 group had significantly longer disease free survival (DFS) than the high ERCC1 group (29.1 vs. 21.0 months, P < 0.0001); in the surgery alone and postoperative platinum-containing chemotherapy subgroups, DFS was significantly longer for the low ERCC1 groups than high ERCC1 groups (30.2 vs. 25.1 months, P = 0.018; 27.0 vs. 19.4 months, P < 0.0001, respectively). In gastric cancer patients receiving surgery alone, the low ERCC1 group had significantly longer overall survival than the high ERCC1 group (47.54 vs. 27.47 months, P = 0.018).

Conclusions: High ERCC1 mRNA expression of the NSCLC tumor tissues was associated with poor disease-free survival (DFS), in both the surgery alone and postoperative platinum-containing chemotherapy subgroups. Meanwhile, low ERCC1 mRNA expression had significantly longer overall survival in gastric cancer patients receiving surgery alone. Therefore, ERCC1 expression was a prognostic factor and predictive marker in NSCLC, and gastric cancer after surgery alone, but was not a prognostic factor in breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314004PMC
October 2015

Synthesis and properties of a clean and sustainable deicing additive for asphalt mixture.

PLoS One 2015 27;10(1):e0115721. Epub 2015 Jan 27.

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan, 430070, PR China.

A clean and sustainable deicing additive was prepared via the adsorption of acetate anions (Ac-) by magnesium (Mg) and aluminum (Al) calcined layered double hydroxide (Mg/Al-CLDH). Fourier transform infrared spectroscopy spectrums proved that Ac- had intercalated into LDH structure. X-ray diffraction patterns, scanning electron microscopy and transmission electron microscopy images showed that the intercalation spacing and platelet thickness of Mg and Al layered double hydroxide containing Ac- anions (Mg/Al-Ac- LDH) had been enlarged due to substitution of divalent CO32- anions by a larger quantity of monovalent Ac- anions. Differential scanning calorimetry tests testified that the insoluble Mg2/Al-Ac- LDH evidently decreased the freeze point (FP) of water to -10.68°C. X-ray photoelectron spectroscopy analyses confirmed that the Ac- were strongly confined by the metal layers of LDHs. FP test of asphalt mixtures confirmed that Mg/Al-Ac- LDHs reduced FP to -5.5°C. Immersion test results indicated that Mg/Al-Ac- LDH had a good deicing durability and Ac- did not released from asphalt mixture. Snow melting observation was conducted further testified that Mg/Al-Ac- LDH melted snow or ice sustainably.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115721PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307978PMC
January 2016

Global transcriptomics identification and analysis of transcriptional factors in different tissues of the paper mulberry.

BMC Plant Biol 2014 Aug 20;14:194. Epub 2014 Aug 20.

Background: The paper mulberry (Broussonetia papyifera) is one of the multifunctional tree species in agroforestry system and is also commonly utilized in traditional medicine in China and other Asian countries. To identify the transcription factors (TFs) and comprehensively understand their regulatory roles in the growth of the paper mulberry, a global transcriptomics TF prediction and the differential expression analysis among root, shoot and leaf were performed by using RNA-seq.

Results: Results indicate that there is 1, 337 TFs encoded by the paper mulberry and they belong to the 55 well-characterized TF families. Based on the phylogenetic analysis, the TFs exist extensively in all organisms are more conservative than those exclusively exist in plant and the paper mulberry has the closest relationship with the mulberry. According to the results of differential expression analysis, there are 627 TFs which exhibit the differential expression profiles in root, shoot and leaf. ARR-Bs, ARFs, NACs and bHLHs together with other root-specific and highly expressed TFs might account for the developed lateral root and unconspicuous taproot in the paper mulberry. Meanwhile, five TCPs highly expressed in shoot of the paper mulberry might negatively regulate the expression of 12 LBDs in shoot. Besides, LBDs, which could directly or indirectly cooperate with ARFs, bHLHs and NACs, seem to be the center knot involving in the regulation of the shoot development in the paper mulberry.

Conclusions: Our study provides the comprehensive transcriptomics identification of TFs in the paper mulberry without genome reference. A large number of lateral organ growth regulation related TFs exhibiting the tissue differential expression may entitle the paper mulberry the developed lateral roots, more branches and rapid growth. It will increase our knowledge of the structure and composition of TFs in tree plant and it will substantially contribute to the improving of this tree.
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http://dx.doi.org/10.1186/s12870-014-0194-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205299PMC
August 2014

Sensitive detection of EGFR mutations in cerebrospinal fluid from lung adenocarcinoma patients with brain metastases.

J Mol Diagn 2014 Sep 30;16(5):558-563. Epub 2014 Jun 30.

Respiratory Oncology Center, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Epidermal growth factor receptor (EGFR) mutations in cerebrospinal fluid (CSF) might be useful predictive markers for EGFR tyrosine kinase inhibitor treatment of intracranial metastatic tumors. In this retrospective study, amplification refractory mutation system (ARMS)-PCR assays were used to investigate the EGFR gene status in 30 lung adenocarcinoma patients with brain metastases. A total of 16 patients tested positive for EGFR-activating mutations in CSF or tumor tissues. These included L858R mutation in exon 21 in six CSF samples and exon 19 deletions in seven CSF samples. EGFR mutations were detected between CSF and primary tumor samples with a 75% positive predictive value (95% CI, 0.45-1.00), 75% negative predictive value (95% CI, 0.51-0.99), 67% sensitivity (95% CI, 0.36-0.97), and 82% specificity (95% CI, 0.59-1.00). Most of the patients who had EGFR mutations in CSF achieved good responses with EGFR-tyrosine kinase inhibitor treatment. In conclusion, ARMS-PCR could be a sensitive method of detecting EGFR mutations in the CSF of patients with lung adenocarcinoma with brain metastases. As such, ARMS-PCR could play an important role in guiding EGFR-tyrosine kinase inhibitor treatments of intracranial tumors and for diagnosing brain metastases in patients with lung adenocarcinoma.
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http://dx.doi.org/10.1016/j.jmoldx.2014.04.008DOI Listing
September 2014

Erlotinib in combination with pemetrexed/cisplatin for leptomeningeal metastases and cerebrospinal fluid drug concentrations in lung adenocarcinoma patients after gefitinib faliure.

Target Oncol 2015 Mar 2;10(1):135-40. Epub 2014 Jul 2.

Department of Respiratory Oncology, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital, Guangzhou Medical University, 510120, Guangzhou, China.

Limited treatment options are available for lung cancer with brain metastases. Recent reports indicated that erlotinib and pemetrexed had synergistic effects in lung adenocarcinoma. Thus, we speculated that erlotinib plus pemetrexed/cisplatin may be more effective for the treatment of refractory central nervous system metastases in patients after gefitinib failure. Six lung adenocarcinoma patients with leptomeningeal metastasis (LM) who showed initial good response to gefitinib and subsequent gefitinib resistance were enrolled in this retrospective study. Five of the six patients had an epidermal growth factor receptor (EGFR) mutation in the primary tumor tissues or plasma. One patient showed complete remission, two patients showed a partial response, and two patients had stable disease. Performance and symptoms improved in the six patients. The survival time after the combination therapy was from 8 to 15 months (median, 9 months). There was no significant difference in cerebrospinal fluid (CSF) penetration rates of erlotinib between the erlotinib-only and the combination groups (P = 0.44). Erlotinib combined with pemetrexed/cisplatin may be effective in the treatment of LM in EGFR mutation patients after gefitinib failure. Small but measurable penetration of erlotinib and pemetrexed into the CSF was observed.
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http://dx.doi.org/10.1007/s11523-014-0326-9DOI Listing
March 2015

Association between epidermal growth factor receptor gene copy number and ERCC1, BRCA1 protein expression in Chinese patients with non-small cell lung cancer.

Med Oncol 2014 Mar 23;31(3):803. Epub 2014 Jan 23.

Department of Cardiothoracic Surgery, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Mutation in epidermal growth factor receptor (EGFR) gene may predict response to chemotherapy in non-small cell lung cancer (NSCLC). However, the correlation between EGFR gene copy status and protein levels of drug-resistant genes, such as excision repair cross-complementing 1 (ERCC1) and breast cancer 1 (BRCA1), remains unclear. We retrospectively analyzed formalin-fixed, paraffin-embedded tumor tissues from 109 Chinese patients with NSCLC. EGFR gene copy number was evaluated by fluorescence in situ hybridization (FISH), and protein levels of platinum-resistance-associated genes, including ERCC1 and BRCA1, were determined by immunohistochemical staining. High EGFR gene copy (EGFR FISH-positive) was found in 21.1% of the patients (amplification in 7.3% and high polysomy in 13.8%, respectively). Immunohistochemical analysis revealed that ERCC1 protein expression was not associated with clinicopathological factors, whereas a significantly higher BRCA1 positive rate was found in poorly differentiated tumors (P=0.02). Further association studies demonstrated that EGFR gene copy number status was not correlated with protein levels of ERCC1 or BRCA1; however, expression of ERCC1 was significantly associated with that of BRCA1 in this set of Chinese patients with NSCLC (P<0.001, r=0.484). Our study demonstrated that EGFR gene copy number status was not correlated with ERCC1 or BRCA1 protein expression, but ERCC1 protein levels were significantly correlated to BRCA1 protein expression levels in tumor tissues from Chinese patients with NSCLC.
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http://dx.doi.org/10.1007/s12032-013-0803-5DOI Listing
March 2014

Bilateral pneumothorax after bevacizumab-containing chemotherapy in fibrosarcoma.

J Thorac Dis 2012 Apr;4(2):229-31

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, No. 151, Yanjiang Rd, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.3978/j.issn.2072-1439.2012.01.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378222PMC
April 2012

Successful treatment of gefitinib-induced acute interstitial pneumonitis with corticosteroid and non-invasive BIPAP-ventilation.

J Thorac Dis 2012 Jun;4(3):316-9

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, No. 151, Yanjiang Rd, Guangzhou, 510120, China.

This is the case of a 63 year-old male who was diagnosed adenocarcinoma in the left upper lung with ipsilateral malignant pleural effusion. At diagnosis it had already spread to left pulmonary HLN (hilar lymph node) and left supraclavicular lymph node and mediastinal lymph nodes. The patient received combined chemotherapy with bevacizumab and GP (gemcitabine and carboplatin) for 6 courses. Disease progression on chest CT scan was recognized, daily treatment with oral gefitinib (250 mg/day) was commenced. One week later, he was admitted under the impression of gefitinib-related interstitial pneumonitis, gefitinib was discontinued immediately and methylprednisolone with BIPAP assisted ventilation were used. The patient was followed up for 2 months after the start of treatment with corticosteroids and BIPAP assisted ventilation and remained well.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2012.03.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378190PMC
June 2012

[Gemcitabine in RRM1-negative advanced refractory non-small cell lung cancer (NSCLC): a case report].

Zhongguo Fei Ai Za Zhi 2011 Jun;14(6):550-3

Department of Cardiothoracic Surgery, Guangzhou Institution of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, China.

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http://dx.doi.org/10.3779/j.issn.1009-3419.2011.06.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999889PMC
June 2011