Publications by authors named "Haijuan Wang"

58 Publications

Screening maize (Zea mays L.) varieties with low accumulation of cadmium, arsenic, and lead in edible parts but high accumulation in other parts: a field plot experiment.

Environ Sci Pollut Res Int 2021 Feb 28. Epub 2021 Feb 28.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.

To find maize varieties with both safe production and soil remediation, 11 maize varieties were planted in field soil which was combinedly polluted by cadmium (Cd), arsenic (As), and lead (Pb). The plant growth, accumulation, phytochemical forms, and translocation of Cd, As, and Pb in different tissues were examined. Furthermore, maize varieties with low metal accumulation in their edible parts but high accumulation in other parts were selected as remediation candidates and pollution-safe varieties. The results showed that the growth of varieties Yayu69, Longhuang2502, and Shennongyu10 were the least affected by heavy metals. The concentrations of Cd, As, and Pb in all of the tested maize grains met the national feed hygiene standards, and the grain concentrations of the three metals in Yayu69, Shengnongyu10, and Yunrui62 all met the national food safety standards. According to the extraction efficiency of Cd, As, and Pb and heavy metal concentrations in grains, four types of maize were classified as follows: (1) the first category was suitable for both soil remediation and safe production, including the varieties Yayu69 (Cd, Pb), Jinyi418 (As, Cd), and Shengnongyu10 (Pb); (2) the second category had a high concentration of metals in edible part but did not exceed the limiting value in national feed hygiene standards, and the metal extraction efficiency was also high, including Beiyu1521 (Cd) and Longhuang2502 (Cd, As, Pb); (3) the third category included heavy metal exclusion varieties with low metals accumulation, such as Yayu749 (Cd), Yunrui62 (As, Pb), and Yunrui8 (As); and (4) the fourth type covered risk maize varieties with food safety risks and unsuitable cultivation at sites polluted with toxic metals, including Chuangui1586 (Pb) and Enyu69 (As). The variety Yayu69 (a Cd/Pb low accumulator in grain) contained a low percentage of inorganic (F) and water-soluble (F) Cd (4%) and Pb (6%) in roots, respectively, but the percentage of F and F Cd and Pb in the variety Beiyu1521 (a Cd/Pb high accumulator in grain) was up to 29% and 13%. Our results provided a new perspective in applying maize varieties with different metal-accumulating ability in their different parts to achieve the remediation of metal-polluted soil and the sustainable development of agricultural production.
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http://dx.doi.org/10.1007/s11356-021-12958-yDOI Listing
February 2021

CDK12 inhibition enhances sensitivity of HER2+ breast cancers to HER2-tyrosine kinase inhibitor via suppressing PI3K/AKT.

Eur J Cancer 2021 Mar 9;145:92-108. Epub 2021 Jan 9.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

Background: Alhtough anti-HER2 tyrosine kinase inhibitors (TKIs) have radically prolonged survival and improved prognosis in HER2-positive breast cancer patients, resistance to these therapies is a constant obstacle leading to TKIs treatment failure and tumour progression.

Methods: To develop new strategies to enhance TKIs efficiency by combining synergistic gene targets, we performed panel library screening using the CRISPR/Cas9 knockout technique based on data mining across TCGA data sets and verified the candidate target in preclinical models and breast cancer high-throughput sequencing data sets.

Results: We identified that CDK12, co-amplified with HER2 in a high frequency, is powerful to sensitise or resensitise HER2-positive breast cancer to anti-HER2 TKIs lapatinib, evidenced by patient-derived organoids in vitro and cell-derived xenograft or patient-derived xenograft in vivo. Exploring mechanisms, we found that inhibition of CDK12 attenuated PI3K/AKT signal, which usually serves as an oncogenic driver and is reactivated when HER2-positive breast cancers develop resistance to lapatinib. Combining CDK12 inhibition exerted additional suppression on p-AKT activation induced by anti-HER2 TKIs lapatinib treatment. Clinically, via DNA sequencing data for tumour tissue and peripheral blood ctDNA, we found that HER2-positive breast cancer patients with CDK12 amplification responded more insensitively to anti-HER2 treatment than those without accompanying CDK12 amplification by harbouring a markedly shortened progression-free survival (PFS) (median PFS: 4.3 months versus 6.9 months; hazards ratio [HR] = 2.26 [95% confidence interval [CI] = 1.32-3.86]; P = 0.0028).

Conclusions: Dual inhibition of HER2/CDK12 will prominently benefit the outcomes of patients with HER2-positive breast cancer by sensitising or resensitising the tumours to anti-HER2 TKIs treatment.
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http://dx.doi.org/10.1016/j.ejca.2020.11.045DOI Listing
March 2021

Diterpenoids from the Whole Plants of Ajuga nipponensis and Their Inhibition of RANKL-Induced Osteoclastogenesis.

Chem Biodivers 2021 Jan 16;18(1):e2000780. Epub 2020 Dec 16.

d Guangdong Provincial Cosmetics Engineering and Technology Research Center, School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, 528458, P. R. China.

Two new diterpenoids, ajudecunoid A (1) and ajudecunoid B (14), along with thirteen known diterpenoids, were isolated from the whole plants of Ajuga nipponensis Makino. Their structures were elucidated by the extensive spectroscopic analysis (UV, IR, MS, and NMR). The absolute configurations of ajudecunoid A (1) and ajudecunoid B (14) were defined through analysis of X-ray crystallography. Fifteen compounds were evaluated for inhibition of the formation of osteoclasts in bone marrow-derived macrophages (BMM) cells. Two neo-clerodane diterpenoids ajuganipponin B (5) and (12S)-6α,19-diacetoxy-18-chloro-4α-hydroxy-12-tigloyloxy-neo-clerod-13-en-15,16-olide (12) showed significant inhibition of osteoclastogenesis with IC values of 0.88 and 0.79 μM, respectively. Here we firstly reported diterpenoids with anti-osteoclastogenesis activity from A. nipponensis.
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http://dx.doi.org/10.1002/cbdv.202000780DOI Listing
January 2021

Chromatin modifier MTA1 regulates mitotic transition and tumorigenesis by orchestrating mitotic mRNA processing.

Nat Commun 2020 09 8;11(1):4455. Epub 2020 Sep 8.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Dysregulated alternative splicing (AS) driving carcinogenetic mitosis remains poorly understood. Here, we demonstrate that cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, broadly interacts and co-expresses with RBPs across cancers, contributing to cancerous mitosis-related AS. Using developed fCLIP-seq technology, we show that MTA1 binds abundant transcripts, preferentially at splicing-responsible motifs, influencing the abundance and AS pattern of target transcripts. MTA1 regulates the mRNA level and guides the AS of a series of mitosis regulators. MTA1 deletion abrogated the dynamic AS switches of variants for ATRX and MYBL2 at mitotic stage, which are relevant to mitosis-related tumorigenesis. MTA1 dysfunction causes defective mitotic arrest, leads to aberrant chromosome segregation, and results in chromosomal instability (CIN), eventually contributing to tumorigenesis. Currently, little is known about the RNA splicing during mitosis; here, we uncover that MTA1 binds transcripts and orchestrates dynamic splicing of mitosis regulators in tumorigenesis.
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http://dx.doi.org/10.1038/s41467-020-18259-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479136PMC
September 2020

Corrigendum to 'ad-PUMA sensitizes drug-resistant choriocarcinoma cells to chemotherapeutic agents' [Gynecologic Oncology 107 (2007) 505-512].

Gynecol Oncol 2020 Nov 20;159(2):597. Epub 2020 Aug 20.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, China. Electronic address:

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http://dx.doi.org/10.1016/j.ygyno.2020.08.007DOI Listing
November 2020

Cancer metastasis-associated protein 1 localizes to the nucleolus and regulates pre-rRNA synthesis in cancer cells.

J Cell Biochem 2021 Feb 12;122(2):180-188. Epub 2020 Aug 12.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Metastasis-associated protein 1 (MTA1) is a critical component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA1 has several biological functions, and it is closely associated with the malignant properties of human cancers; however, the mechanisms and subcellular localization of MTA1 in cells remain unclear. Some initial studies indicated that MTA1 was absent from the nucleolus; however, several NuRD components were recently found to be present in the nucleolus, where they regulate preribosomal RNA (pre-rRNA) transcription. In this study, we demonstrated that MTA1 is definitely localized to the nucleolus and regulates pre-rRNA transcription, which is consistent with the recent reports on NuRD. To determine if MTA1 was present in the nucleolus, we utilized the following complementary molecular approaches: immunofluorescence, GFP-tag tracking, immunoelectron microscopy, and immunoprecipitation (IP). To examine the role of MTA1 in rRNA synthesis, we performed quantitative polymerase chain reaction analysis. We revealed that both endogenous and exogenous MTA1 showed apparent granule-like nucleolar subcellular localization. MTA1 interacts with two major resident nucleolar proteins, nucleolin and nucleophosmin. Immunofluorescent colocalization analyses showed that MTA1 localizes to the fibrillarin-deficient regions of the nucleolus, and Co-IP experiments indicated that there was no interaction between MTA1 and fibrillarin; further, fibrillarin was not identified in the MTA1 interactome. Loss- and gain-of-function studies indicated that MTA1 promotes pre-rRNA transcription in cancer cells. Collectively, our data identify MTA1 as a novel nucleolar protein, and activation of pre-rRNA transcription in cancer cells may be an alternative mechanism by which MTA1 promotes malignancies.
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http://dx.doi.org/10.1002/jcb.29837DOI Listing
February 2021

Effect of soil washing on heavy metal removal and soil quality: A two-sided coin.

Ecotoxicol Environ Saf 2020 Oct 15;203:110981. Epub 2020 Jul 15.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China; Yunnan Key Lab of Soil Carbon Sequestration and Pollution Control, Kunming, 650500, China. Electronic address:

Heavy metal contamination in soil due to human activities is a global environmental problem. To find a washing solution that can significantly decontaminate heavy metals and minimize damage to soil quality, six washing solutions (HPO, KCO, CHCOOK, KHPO, HNO and KNO) were used at different concentrations to treat contaminated soil collected from the field. Furthermore, changes in soil physicochemical properties and heavy metal speciation among prewashed, postwashed and neutralized samples were tested. Additionally, soil enzyme activities and soil microbial diversities in contaminated soil among the prewashed, postwashed and neutralized samples were also measured. Finally, a pot experiment was conducted with Mentha haplocalyx to test the efficiency of soil washing. The results revealed that the optimum washing solution was 1% HNO and that the removal rates of Cd and Pb were 75.7% and 60.6%, respectively, under treatment conditions of 35 °C, 90 min and a solid-liquid ratio of 1:10. The pH, total phosphorous, available potassium, soil enzyme activities and soil microbial diversity decreased significantly after washing. However, after the neutralization of washed soil with Ca(OH), the available phosphorous, total nitrogen and some microorganisms increased significantly compared with those of the soil before washing. After treatment with 1% HNO, the chemical forms of Cd and Pb in soil mainly existed as F (exchangeable) fractions, but the main forms of the two metals changed to F (residual) and F (bound to Fe-Mn oxides) fractions after neutralization with Ca(OH). In addition, the plant height, root length, and fresh and dry weight of M. haplocalyx were not significantly affected by soil neutralization, while the Pb, Cu and As concentrations in the aboveground parts significantly decreased. Therefore, although soil washing could effectively remove Pb and Cd in soil, it also resulted in a significant decline in soil quality, but soil neutralization could effectively alleviate the negative effects during soil washing.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110981DOI Listing
October 2020

Chance to rein in a cancer--Spontaneous regression of lung carcinoma (1988-2018): a 30-year perspective.

Int J Clin Exp Pathol 2020 1;13(5):1190-1196. Epub 2020 May 1.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021, China.

Background: Spontaneous regression of tumor is an extremely rare phenomenon in the oncology field and even rarer for lung cancer. However, the underlying mechanism is poorly understood. Summarizing the available clinical information and the supposed mechanism shed new light on lung cancer therapy strategies in the new era of immunotherapy.

Summary: We conducted a PubMed search using the retrieval tactics ("Lung Neoplasms" [Mesh]) AND "Neoplasm Regression, Spontaneous" [Mesh] for reports from 1988 to January 2018, and all references in the relevant literature were subsequently investigated for relevance. Using the criteria of Everson and Cole, 14 cases were finally defined as spontaneous regression and were reviewed in the research. Key messages: The information regarding patient characteristics, treatments, and follow-up has been summarized. In this review, we found that spontaneous lung cancer regression cases fall into two categories including: (1) neurologic disorders in 6 cases, half of whom suffered with paraneoplastic neurological syndromes (PNS) and (2) immunological reactions in 7 cases. Getting data on more spontaneous regression cases and more detailed information will definitely help us understand the mechanism for the body's surveillance system-cancer balance, creating a big chance to increase cancer immunotherapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270659PMC
May 2020

Re-investigation of cadmium accumulation in Mirabilis jalapa L.: evidences from field and laboratory.

Environ Sci Pollut Res Int 2020 Apr 25;27(11):12065-12079. Epub 2020 Jan 25.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, Yunnan, China.

Mirabilis jalapa L. was identified as a cadmium (Cd) hyperaccumulator, but data were mainly from laboratory conditions. The main aim of the present study was to confirm whether M. jalapa is a Cd hyperaccumulator by field survey and laboratory experiment. The field survey was conducted at 3 sites and 66 samples were collected, and the results showed that although M. jalapa did not exhibit any visible damage when growing on soil containing 139 mg Cd kg, a low concentration of Cd (11.85 ± 3.45 mg kg) in its leaves was observed. Although the translocation factor (TF) was up to 3.24 ± 0.42, the bioconcentration factor (BCF) was only 0.13 ± 0.07. The Cd accumulation in leaves of Lanping (LP, contaminated site) and Kunming (KM, clean site) populations reached 93.88 and 81.76 mg kg when artificially spiked soil Cd was 175 mg kg, respectively. The BCFs of LP and KM populations were 0.55 and 0.48, and the TFs of the two populations were 3.98 and 4.15, respectively. Under hydroponic condition, the Cd concentration in young leaves of LP and KM populations was 78.5 ± 0.8 and 46.3 ± 1.2 mg kg at 5 mg L Cd treatment, respectively. Furthermore, a significantly positive correlation between tissue Cd concentration and total Cd, CaCl-extractable Cd, and TCLP-Cd (toxicity characteristic leaching procedure) in soil was established. Therefore, M. jalapa had constitutional characteristics for Cd tolerance and accumulation, but it was not a Cd hyperaccumulator.
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http://dx.doi.org/10.1007/s11356-020-07785-6DOI Listing
April 2020

Indole-3-acetic acid promotes cadmium (Cd) accumulation in a Cd hyperaccumulator and a non-hyperaccumulator by different physiological responses.

Ecotoxicol Environ Saf 2020 Mar 21;191:110213. Epub 2020 Jan 21.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China; Yunnan Key Lab of Soil Carbon Sequestration and Pollution Control, Kunming, 650500, China. Electronic address:

To study the effects of indole-3-acetic acid (IAA) on cadmium (Cd) accumulation and the physiological responses of the Cd hyperaccumulator Solanum nigrum and non-hyperaccumulator Solanum melongena, a pot experiment was conducted in soil containing 2 mg kg Cd in which different concentrations of IAA (0, 10, 20, or 40 mg L) were sprayed on plant leaves. The results showed that Cd accumulation in shoots of S. nigrum was significantly increased by 30% after the addition of 10 mg L IAA under 2 mg kg Cd stress compared to that in the control, but shoot Cd accumulation showed no significant change in S. melongena after this IAA treatment. Additionally, the growth and the proline content in the two species were significantly increased by 20 mg L IAA. The activities of peroxidase and catalase in leaves of S. nigrum and the activity of superoxide dismutase (SOD) in S. melongena were significantly increased and their malondialdehyde content was significantly decreased compared to those in the control. The root activity of S. nigrum was significantly improved after 10 and 20 mg L IAA treatments, but no significant difference was observed in S. melongena. The correlation analysis results showed that the Cd concentration in leaves of S. nigrum was significantly and positively correlated with the carotenoid and proline contents, and there was also a significant positive correlation between the Cd concentration and SOD activity in leaves of S. melongena. Therefore, S. nigrum is an ideal plant for the phytoextraction of Cd-contaminated soil assisted by IAA. IAA promotes Cd accumulation in plant shoots by enhancing the accumulation of carotenoids and proline in S. nigrum and maintaining a high leaf SOD activity in S. melongena.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110213DOI Listing
March 2020

LncRNA PTCSC3 Inhibits Tumor Growth and Cancer Cell Stemness in Gastric Cancer by Interacting with lncRNA Linc-pint.

Cancer Manag Res 2019 11;11:10393-10399. Epub 2019 Dec 11.

Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, People's Republic of China.

Background: The tumor suppressor role of lncRNA PTCSC3 has been reported in papillary thyroid carcinoma, our study aimed to investigate its involvement in gastric cancer.

Methods: Tumor tissues and adjacent healthy tissues were collected from gastric cancer patients. Expression of PTCSC3 and lncRNA Linc-pint in these tissues was analyzed by RT-qPCR. The interaction between PTCSC3 and Linc-pint was analyzed by overexpression experiments. Cell proliferation and stemness were analyzed by CCK-8 assay and cell stemness assay, respectively.

Results: PTCSC3 and lncRNA Linc-pint were both downregulated in tumor tissues than in adjacent healthy tissues of gastric cancer patients. Low levels of PTCSC3 and Linc-pint were closely correlated with poor survival. PTCSC3 and Linc-pint overexpression inhibited tumor growth and cancer cell stemness, while Linc-pint knockdown played an opposite role an attenuated the effects of PTCSC3 overexpression. Expression levels of PTCSC3 and Linc-pint were significantly correlated in tumor tissues but not in adjacent healthy tissues. Overexpression of PTCSC3 and Linc-pint upregulated the expression of each other.

Conclusion: PTCSC3 inhibits tumor growth and cancer cell stemness in gastric cancer by interacting with lncRNA Linc-pint.
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http://dx.doi.org/10.2147/CMAR.S231369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911807PMC
December 2019

A TGF-β-MTA1-SOX4-EZH2 signaling axis drives epithelial-mesenchymal transition in tumor metastasis.

Oncogene 2020 03 6;39(10):2125-2139. Epub 2019 Dec 6.

Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.

MTA1, SOX4, EZH2, and TGF-β are all potent inducers of epithelial-mesenchymal transition (EMT) in cancer; however, the signaling relationship among these molecules in EMT is poorly understood. Here, we investigated the function of MTA1 in cancer cells and demonstrated that MTA1 overexpression efficiently activates EMT. This activation resulted in a significant increase in the migratory and invasive properties of three different cancer cell lines through a common mechanism involving SOX4 activation, screened from a gene expression profiling analysis. We showed that both SOX4 and MTA1 are induced by TGF-β and both are indispensable for TGF-β-mediated EMT. Further investigation identified that MTA1 acts upstream of SOX4 in the TGF-β pathway, emphasizing a TGF-β-MTA1-SOX4 signaling axis in EMT induction. The histone methyltransferase EZH2, a component of the polycomb (PcG) repressive complex 2 (PRC2), was identified as a critical responsive gene of the TGF-β-MTA1-SOX4 signaling in three different epithelial cancer cell lines, suggesting that this signaling acts broadly in cancer cells in vitro. The MTA1-SOX4-EZH2 signaling cascade was further verified in TCGA pan-cancer patient samples and in a colon cancer cDNA microarray, and activation of genes in this signaling pathway predicted an unfavorable prognosis in colon cancer patients. Collectively, our data uncover a SOX4-dependent EMT-inducing mechanism underlying MTA1-driven cancer metastasis and suggest a widespread TGF-β-MTA1-SOX4-EZH2 signaling axis that drives EMT in various cancers. We propose that this signaling may be used as a common therapeutic target to control epithelial cancer metastasis.
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http://dx.doi.org/10.1038/s41388-019-1132-8DOI Listing
March 2020

MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway.

Carcinogenesis 2020 Sep;41(9):1263-1272

National Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Metastasis-associated protein 1 (MTA1) is upregulated in multiple malignancies and promotes cancer proliferation and metastasis, but whether and how MTA1 promotes esophageal squamous cell carcinoma (ESCC) tumorigenesis remain unanswered. Here, we established an ESCC model in MTA1 transgenic mice induced by the chemical carcinogen 4-nitroquinoline 1-oxide (4-NQO) and found that MTA1 promotes ESCC tumorigenesis in mice. MTA1 overexpression was observed in ESCC cells and clinical ESCC samples. Overexpressed MTA1 increased colony formation and the invasiveness and migration of ESCC cells, whereas knock down of MTA1 in ESCC cells significantly decreased colony formation, invasion and migration in vitro and inhibited the growth of xenograft tumors in vivo. RNA sequencing (RNA-seq) analysis combined with western blot assays revealed that MTA1 promotes carcinogenesis by enhancing MEK/ERK/p90RSK signaling. The phosphorylation of MEK, ERK and their downstream target p90RSK was significantly decreased after MTA1 knockdown in ESCC cells and was increased in MTA1-overexpressing cells. Moreover, colony formation, invasion and migration potential were dramatically suppressed when cells overexpressing MTA1 were treated with MEK (PD0325901) or ERK (SCH772948) inhibitors. In conclusion, MTA1 plays a pivotal oncogenic role in ESCC tumorigenesis and development through activating the MEK/ERK/p90RSK pathway.
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http://dx.doi.org/10.1093/carcin/bgz200DOI Listing
September 2020

Linc‑pint overexpression inhibits the growth of gastric tumors by downregulating HIF‑1α.

Mol Med Rep 2019 Sep 25;20(3):2875-2881. Epub 2019 Jul 25.

Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050019, P.R. China.

Long intergenic non‑protein coding RNA, p53 induced transcript (Linc‑pint) has been reported to be downregulated in various cancer cell lines; however, its expression profile and role in gastric cancer remains unknown. The present study aimed to investigate the involvement of Linc‑pint in gastric cancer. Through quantitative polymerase chain reaction, western blotting and viability assays, it was observed that Linc‑pint expression was significantly downregulated in gastric biopsies from patients with gastric cancer, compared with healthy controls. Conversely, the expression of hypoxia‑inducible factor‑1α (HIF‑1α) mRNA was significantly upregulated in patients with gastric cancer compared with in healthy controls. Using a variety of statistical inference tests, including receiver operating characteristic curve and correlation analyses, it was determined that the expression levels of Linc‑pint and HIF‑1α exhibited a significantly negative correlation in patients with gastric cancer but not in healthy controls. Linc‑pint expression was significantly and inversely associated with tumor size but not tumor metastasis. Linc‑pint overexpression inhibited the proliferation of gastric cancer cells, whereas treatment with exogenous HIF‑1α promoted proliferation. Linc‑pint overexpression downregulated the expression of HIF‑1α, whereas exogenous HIF‑1α did not significantly alter Linc‑pint expression. Furthermore, treatment with exogenous HIF‑1α suppressed the inhibitory effects of Linc‑pint overexpression on the proliferation of gastric cancer cells. In conclusion, overexpression of Linc‑pint may inhibit the growth of gastric tumors via downregulation of HIF‑1α.
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http://dx.doi.org/10.3892/mmr.2019.10531DOI Listing
September 2019

Heavy metal pollution and potential health risks of commercially available Chinese herbal medicines.

Sci Total Environ 2019 Feb 30;653:748-757. Epub 2018 Oct 30.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.

A survey was conducted to investigate the pollution and health risks of copper (Cu), cadmium (Cd), lead (Pb), arsenic (As), mercury (Hg) and zinc (Zn) in 60 Chinese herbal medicines (CHMs) collected from a market in Kunming City, Yunnan Province, China. Furthermore, eight CHMs (Cyathulae radix, Drynariae rhizoma, Peucedani radix, Homalomenae rhizoma, Dryopteris setosa, Polygonati rhizoma, Lilii bulbus, and Linderae radix) containing high Cd concentrations were selected to further analyse their Cd chemical forms. Additionally, the dissolution rates of six heavy metals in decoction liquid were also analysed for four CHMs (Typhonii rhizoma, Linderae radix, Homalomenae rhizoma, and Cyathulae radix), and the health risks of heavy metals in CHMs were evaluated. The results showed that the Cd, Hg and Cu concentrations in the 60 CHMs exceeded the limiting values of the "Green Trade Standards of Importing & Exporting Medicinal Plants & Preparations" (WM2-2001), with exceedance ratios of 38.8%, 8.3% and 1.7%, respectively. The majority of Cd was integrated with pectates and protein in CHMs, and the other five Cd chemical forms followed the order of water-soluble > insoluble heavy metal phosphates > oxalate > residual > inorganic form, indicating that Cd had relatively low bioactivity and toxicity. The average dissolution rates of Zn, Cu, Cd, Hg, As and Pb in the four CHMs were 47.4%, 33.8%, 20.5%, 6.1%, 5.4% and 4.8%, respectively. The calculation results of hazard quotients (HQs) for Cd and Hg showed that the CHMs did not pose a threat to human health.
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http://dx.doi.org/10.1016/j.scitotenv.2018.10.388DOI Listing
February 2019

Effect of arsenate on endogenous levels of cytokinins with different existing forms in two Pteris species.

Plant Physiol Biochem 2018 Nov 10;132:652-659. Epub 2018 Oct 10.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, China.

Our previous results showed that content of trans-zeatin (tZ) increases in leaves of heavy metal hyperaccumulators but decreases in non-hyperaccumulators growing in multiple heavy metal polluted soils. However, the relationship between arsenic (As) accumulation and endogenous forms of cytokinins (CTKs) in As hyperaccumulators remains unknown. Here a hydroponic experiment was conducted to compare the CTK forms in the As hyperaccumulator Pteris cretica var. nervosa and non-hyperaccumulator Pteris ensiformis under arsenate stress (0, 2, 5, and 10 mg L). A simple and cost-effective procedure for the determination of CTK forms in plants was established, and a stepwise regression analysis was used to study the relationship among total As contents and different forms of endogenous CTKs in fronds of two plants. The results showed that the optimized chromatographic parameters were Zobax SB-C18 column (5 μm × 4.6 mm × 250 mm), UV detection detector at 269 nm, a flow rate of 0.6 mL min, constant temperature of 45 °C and gradient elution with methanol-acetonitrile-1% acetic acid. Contents of chlorophylls in the fronds of P. ensiformis were significantly decreased with addition of As compared to P. cretica var. nervosa. Furthermore, the total As content in fronds of P. cretica var. nervosa was positively correlated to the contents of N6-(2-isopentenyl) adenine-7-β-D-glucoside (iP7G) and N6-(2-isopentenyl) adenosine (iPR). However, the total As content in fronds of P. ensiformis was negatively correlated to its trans-zeatin riboside (ZR) content. Therefore, iP7G and iPR could positively improve As accumulation by P. cretica var. nervosa.
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http://dx.doi.org/10.1016/j.plaphy.2018.10.009DOI Listing
November 2018

Inhibitory effect of chidamide on the growth of human adenoid cystic carcinoma cells.

Biomed Pharmacother 2018 Mar 20;99:608-614. Epub 2018 Feb 20.

Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. Electronic address:

Adenoid cystic carcinoma (ACC) is a malignant epithelial neoplasm that limitedly responses to chemotherapy at the cost of significant toxicity. There is no single targeted drug approved by Food and Drug Administration (FDA) for ACC. Genomic landscape studies have revealed that frequently mutated pathways in ACC often involve in chromatin remodeling, which interfere multiple histone related proteins. Chidamide is a novel histone deacetylase inhibitor (HDACi) approved in clinical practice that was designed to increase the acetylation level of histone H3. It demonstrated anticancer effects in various cancers in preclinical study, but not in ACC. In this study, we aimed to investigate the anticancer effects of chidamide alone or in combination with cisplatin (cDDP) on ACC in vitro and in vivo. The results showed that chidamide alone or in combination with cDDP effectively inhibited the growth and proliferation of ACC cells in a dose- and time-dependent manner. Chidamide arrested cell cycle in G2/M phase by up-regulating the acetylation of histone H3 and interfering phosphorylation of AKT protein. Chidamide alone or in combination with cDDP did not induce distinct apoptosis in ACC cells. In vivo experiments showed that chidamide combining cDDP exerted significant inhibitory effects on ACC. These suggest that chidamide may be a promising candidate drug for the treatment of patients with ACC.
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http://dx.doi.org/10.1016/j.biopha.2018.01.110DOI Listing
March 2018

Effects of kinetin on plant growth and chloroplast ultrastructure of two Pteris species under arsenate stress.

Ecotoxicol Environ Saf 2018 Aug 12;158:37-43. Epub 2018 Apr 12.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, Yunnan, China.

Cytokinins (CTKs) are effective in alleviating abiotic stresses on plants, but little information is available regarding the effects of CTKs on arsenic (As) accumulation and changes of chloroplast ultrastructure in plants with different As-accumulating ability. Here a hydroponic experiment was designed to evaluate the effects of different concentration of kinetin (KT, 0-40 mg/L) on growth and chloroplast ultrastructure of As hyperaccumulator Pteris cretica var. nervosa and non-hyperaccumulator Pteris ensiformis treated by 5 mg/L arsenate for 14 days. The growth parameters, As accumulation, contents of photosynthetic pigments and chloroplast ultrastructure were examined. The results showed that KT promoted the growth of two plants, and significantly increased As accumulation and translocation in P. cretica var. nervosa and P. ensiformis at 5 and 20 mg/L, respectively. Additionally, the contents of chlorophyll a and carotenoid in two plants showed no significant difference at 20 mg/L KT compared to the control. Chloroplast ultrastructure of P. cretica var. nervosa was integral with KT application. Comparatively, the swollen chloroplasts were increased, plasmolysis appeared, and chloroplast grana slice layers and stroma lamellas were clearly separated or distorted at 5 mg/L KT in P. ensiformis. The length and width of chloroplasts in P. cretica var. nervosa were significantly increased with KT addition compared to the control. However, the length of chloroplasts in P. ensiformis was significantly decreased but their width showed no significant change. Furthermore, the deterioration of chloroplast ultrastructure in P. ensiformis was ameliorated by 40 mg/L KT. These results suggested that KT increased As accumulation and was beneficial to maintain the photosynthetic pigments for a good growth of plants. Therefore, KT could maintain and reorganize the ultrastructure integrality of As-stressed chloroplasts to some extent for the two plants, especially at high concentration.
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http://dx.doi.org/10.1016/j.ecoenv.2018.04.009DOI Listing
August 2018

Comprehensive evaluation on effective leaching of critical metals from spent lithium-ion batteries.

Waste Manag 2018 May 17;75:477-485. Epub 2018 Feb 17.

Beijing Engineering Research Centre of Process Pollution Control, Division of Environment Technology and Engineering, National Engineering Laboratory for Hydrometallurgical Cleaner Production Technology, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Recovery of metals from spent lithium-ion batteries (LIBs) has attracted worldwide attention because of issues from both environmental impacts and resource supply. Leaching, for instance using an acidic solution, is a critical step for effective recovery of metals from spent LIBs. To achieve both high leaching efficiency and selectivity of the targeted metals, improved understanding on the interactive features of the materials and leaching solutions is highly required. However, such understanding is still limited at least caused by the variation on physiochemical properties of different leaching solutions. In this research, a comprehensive investigation and evaluation on the leaching process using acidic solutions to recycle spent LIBs is carried out. Through analyzing two important parameters, i.e. leaching speed and recovery rate of the corresponding metals, the effects of hydrogen ion concentration, acid species and concentration on these two parameters were evaluated. It was found that a leachant with organic acids may leach Co and Li from the cathode scrap and leave Al foil as metallic form with high leaching selectivity, while that with inorganic acids typically leach all metals into the solution. Inconsistency between the leaching selectivity and efficiency during spent LIBs recycling is frequently noticed. In order to achieve an optimal status with both high leaching selectivity and efficiency (especially at high solid-to-liquid ratios), it is important to manipulate the average leaching speed and recovery rate of metals to optimize the leaching conditions. Subsequently, it is found that the leaching speed is significantly dependent on the hydrogen ion concentration and the capability of releasing hydrogen ions of the acidic leachant during leaching. With this research, it is expected to improve understanding on controlling the physiochemical properties of a leaching solution and to potentially design processes for spent LIBs recycling with high industrial viability.
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http://dx.doi.org/10.1016/j.wasman.2018.02.023DOI Listing
May 2018

A Case of a Newborn With Blocked RhD Antigen and HDFN.

Lab Med 2017 Nov;48(4):381-383

Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.

A group O RhD-negative pregnant patient with anti-D antibody at titer 1:2048 delivered a baby boy by cesarean section at 38 + 6 weeks gestational age. The neonate typed as group O, but D antigen was at first uncertain. DAT and antibody screen of newborn were both positive. Various assays were used for D antigen determination. Ultimately, D antigen blocked by high-titer maternal anti-D antibody was confirmed. Total bilirubin of the newborn was 52.7 umol/L, and hemoglobin was 1.46 mg/dL. O RhD-negative red cells were used for an exchange transfusion.
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http://dx.doi.org/10.1093/labmed/lmx061DOI Listing
November 2017

Aldehyde dehydrogenase 1 (ALDH1) expression is an independent prognostic factor in triple negative breast cancer (TNBC).

Medicine (Baltimore) 2017 Apr;96(14):e6561

Department of Medical Oncology, National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College Department of Medical Oncology, Shandong Cancer Hospital/Institute, Jinan, Shandong Department of Medical Oncology, Beijing Ditan Hospital, Capital Medical University State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Triple negative breast cancer (TNBC) is a subset of breast cancer that is highly aggressive and has a poor prognosis. Meanwhile, cancer stem cells (CSCs) are also characterized by a strong tumorigenic potential, which might be partly responsible for the aggressive behavior of TNBC. We previously showed that CSCs are enriched in TNBC cell lines and tissues. Further experiments in animal models revealed higher tumorigenicity of CSCs sorted from TNBC cell lines. In this study, we aimed to determine the clinical relationship between CSCs and TNBC by exploring the expression of aldehyde dehydrogenase 1 (ALDH1), which is a putative marker of breast CSCs, in TNBC tissues.ALDH1 levels in paraffin-embedded tumor tissues from 158 TNBC patients were evaluated by immunohistochemistry staining using an ALDH1A1 primary antibody. Staining evaluation was performed independently by two pathologists, and the expression level of ALDH1 was evaluated in terms of the percentage and intensity of positive cells. The association of immunohistochemistry staining of ALDH1 expression with clinical parameters was also analyzed.ALDH1 expression in tumor cells was observed in 88 out of 158 cases (55.7%). Analysis of clinicopathological parameters showed that the immunohistochemistry staining of ALDH1 was significantly correlated with tumor size (P = 0.02) and stage (P = 0.04). Survival analysis in patients with ALDH1 expression demonstrated shorter relapse-free survival (RFS) and overall survival (OS) times (P = 0.01; P = 0.001). Moreover, Cox multivariate analysis revealed that ALDH1 expression was an independent prognostic indicator of RFS and OS (P = 0.04; P = 0.04).Immunohistochemistry staining of ALDH1 in tumor cells is an independent prognostic indicator of RFS and OS in TNBC patients.
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http://dx.doi.org/10.1097/MD.0000000000006561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411217PMC
April 2017

A significant positive correlation between endogenous trans-zeatin content and total arsenic in arsenic hyperaccumulator Pteris cretica var. nervosa.

Ecotoxicol Environ Saf 2017 Apr 4;138:199-205. Epub 2017 Jan 4.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan Province 650500, China.

A pot experiment was conducted to compare the content of endogenous trans-zeatin (Z), plant arsenic (As) uptake and physiological indices in the fronds of As-hyperaccumulator (Pteris cretica var. nervosa) and non-hyperaccumulator (Pteris ensiformis). Furthermore, a stepwise regression method was used to study the relationship among determined indices, and the time-course effect of main indices was also investigated under 100mg/kg As stress with time extension. In the 100-200mg/kg As treatments, plant height showed no significant difference and endogenous Z content significantly increased in P. cretica var. nervosa compared to the control, but a significant decrease of height and endogenous Z was observed in P. ensiformis. The concentrations of As (III) and As (V) increased significantly in the fronds of two plants, but this increase was much higher in P. cretica var. nervosa. Compared to the control, the contents of chlorophyll and soluble protein were significantly increased in P. cretica var. nervosa but decreased in P. ensiformis in the 200mg/kg As treatment, respectively. A significant positive correlation was found between the contents of endogenous Z and total As in P. cretica var. nervosa, but such a correlation was not found in P. ensiformis. Additionally, in the time-course effect experiment, a peak value of each index was appeared in the 43rd day in two plants, except for chlorophyll in P. ensiformis, but this value was significantly higher in P. cretica var. nervosa than that in P. ensiformis. In conclusion, a higher endogenous Z content contributed to As accumulation of P. cretica var. nervosa under As stress.
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http://dx.doi.org/10.1016/j.ecoenv.2016.12.031DOI Listing
April 2017

Endogenous trans-zeatin content in plants with different metal-accumulating ability: a field survey.

Environ Sci Pollut Res Int 2016 Dec 9;23(23):23422-23435. Epub 2016 Sep 9.

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, 650500, People's Republic of China.

A field survey was conducted to evaluate soil metal pollution and endogenous trans-zeatin content in the leaves of plants growing at six sites in a metal-polluted area located in Gejiu, Yunnan, China. Five plant species were collected, and the physicochemical properties and concentrations of five metals in the soil were analyzed. The trans-zeatin content in plant leaves was measured by high-performance liquid chromatography. Based on the Nemerow pollution index, the six sites were classified into four levels of pollution (i.e., low, medium, high, and severely high). The degree of soil metal pollution was cadmium (Cd) > arsenic (As) > lead (Pb) > zinc (Zn) > copper (Cu). The leaf trans-zeatin content in Pteris vittata (an arsenic hyperaccumulator) increased significantly by 98.6 % in soil with a severely high level of pollution compared with soil at a low level of pollution. However, in non-hyperaccumulators Bidens pilosa var. radiata and Ageratina adenophora, a significant decrease in leaf trans-zeatin content of 35.6 and 87.6 %, respectively, was observed. The leaf trans-zeatin content in Artemisia argyi also decreased significantly by 73.6 % in high metal-polluted soil compared with that in medium metal-polluted soil. Furthermore, significant correlations were observed between leaf trans-zeatin content in Pteris vittata and As, Pb, and Cd concentrations in the soil; however, either no correlation or a negative one was observed in the other plant species. Therefore, a high content of trans-zeatin in the leaves of Pteris vittata may play an important role in its normal growth and tolerance to metals.
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http://dx.doi.org/10.1007/s11356-016-7544-xDOI Listing
December 2016

Spheres from cervical cancer cells display stemness and cancer drug resistance.

Oncol Lett 2016 Sep 20;12(3):2184-2188. Epub 2016 Jul 20.

State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.

Cervical cancer is one of the most common gynecological malignant tumors and is the cause of a serious health problem worldwide. An increasing amount of evidence has shown that cancer stem cells (CSCs) are present in tumors, and that these CSCs may be responsible for tumor metastasis and relapse. The present study aimed to identify and characterize a CSC population from the CaSki cell line. First, a stem cell culture medium was used to selectively expand the cancer stem-like cell spheres, and the putative stemness markers, Oct4 and Sox2, were identified. These markers were all highly expressed in the CaSki sphere-forming cells. Next, target region amplified polymorphism-polymerase chain reaction was performed and the CaSki sphere-forming cells were found to exhibit higher telomerase activity than the CaSki control cells cultured in non-stem cell medium. Using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, it was found that the CaSki sphere-forming cells were more resistant to chemotherapeutic drugs than the control CaSki cells. Using the tumor invasive assay, it was shown that the CaSki sphere-forming cells were more invasive than the control CaSki cells. These characteristics all suggested that the tumor sphere-forming cells mirrored the acknowledged CSC phenotypes. Overall, the use of a suspended sphere culture of CaSki cells may be an easy and feasible approach for enriching cancer stem-like cells in cervical cancer research.
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http://dx.doi.org/10.3892/ol.2016.4893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998566PMC
September 2016

Effects of indole-3-acetic acid on arsenic uptake and antioxidative enzymes in Pteris cretica var. nervosa and Pteris ensiformis.

Int J Phytoremediation 2017 Mar;19(3):231-238

a Faculty of Environmental Science and Engineering, Kunming University of Science and Technology , Kunming , China.

A hydroponic experiment was conducted to investigate the effects of indole-3-acetic acid (IAA) on arsenic (As) uptake and antioxidative enzymes in fronds of Pteris cretica var. nervosa (As hyperaccumulator) and Pteris ensiformis (non-hyperaccumulator). Plants were exposed to 2 mg L As(III), As(V) or dimethylarsinic acid (DMA) and IAA concentrations for 14 d. The biomass and total As in the plants significantly increased at 30 mg L IAA. Superoxide dismutase (SOD) activities significantly increased with IAA addition. Catalase (CAT) activities showed a significant increase in P. ensiformis exposed to three As species at 30 or 50 mg L IAA but varied in P. cretica var. nervosa. Peroxidase (POD) activities were unchanged in P. ensiformis except for a significant decrease at 50 mg L IAA under As(III) treatment. However, a significant increase was observed in P. cretica var. nervosa at 10 mg L IAA under As(III) or DMA treatment and at 50 mg L IAA under As(V) treatment. Under DMA stress, malondialdehyde contents in fronds of P. cretica var. nervosa showed a significant decrease at 10 mg L IAA but remained unchanged in P. ensiformis. Therefore, IAA enhanced As uptake and frond POD activity in P. cretica var. nervosa under As stress.
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http://dx.doi.org/10.1080/15226514.2016.1207609DOI Listing
March 2017

Inflammation and Inflammatory Cells in Myocardial Infarction and Reperfusion Injury: A Double-Edged Sword.

Clin Med Insights Cardiol 2016 1;10:79-84. Epub 2016 Jun 1.

Department of Physiology, The Fourth Military Medical University, Xi'an, Shaanxi, China.

Myocardial infarction (MI) is the most common cause of cardiac injury, and subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Therefore, inflammation and inflammatory cell infiltration are the hallmarks of MI and reperfusion injury. Ischemic cardiac injury activates the innate immune response via toll-like receptors and upregulates chemokine and cytokine expressions in the infarcted heart. The recruitment of inflammatory cells is a dynamic and superbly orchestrated process. Sequential infiltration of the injured myocardium with neutrophils, monocytes and their descendant macrophages, dendritic cells, and lymphocytes contributes to the initiation and resolution of inflammation, infarct healing, angiogenesis, and ventricular remodeling. Both detrimental effects and a beneficial role in the pathophysiology of MI and reperfusion injury may be attributed to the subset heterogeneity and functional diversity of these inflammatory cells.
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http://dx.doi.org/10.4137/CMC.S33164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892199PMC
June 2016

Bioinformatic exploration of MTA1-regulated gene networks in colon cancer.

Front Med 2016 Jun 6;10(2):178-82. Epub 2016 Apr 6.

Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, State Key Laboratory of Molecular Oncology, Beijing, 100021, China.

Metastasis-associated gene 1 (MTA1) controls a series of biological processes in tumor progression. Tumor progression is a complex process regulated by a gene network. The global cancer gene regulatory network must be analyzed to determine the position of MTA1 in the molecular network and its cooperative genes by further exploring the biological functions of this gene. We used TCGA data sets and GeneCards database to screen MTA1-related genes. GO and KEGG pathway analyses were conducted with DAVID and gene network analysis via STRING and Cytoscape. Results showed that in the development of colon cancer, MTA1 is linked to certain signal pathways, such as Wnt/Notch/nucleotide excision repair pathways. The findings also suggested that MTA1 demonstrates the closest relationship in a coregulation process with the key molecules AKT1, EP300, CREBBP, SMARCA4, RHOA, and CAD. These results lead MTA1 exploration to an in-depth investigation in different directions, such as Wnt, Notch, and DNA repair.
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http://dx.doi.org/10.1007/s11684-016-0442-2DOI Listing
June 2016

The Efficacy and Safety of Programmed Cell Death 1 and Programmed Cell Death 1 Ligand Inhibitors for Advanced Melanoma: A Meta-Analysis of Clinical Trials Following the PRISMA Guidelines.

Medicine (Baltimore) 2016 Mar;95(11):e3134

From the Department of Medical Oncology (XG, FM, ZY, BX), and State Key Laboratory of Molecular Oncology (HW, HQ), Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The purpose of this study was to investigate the efficacy and safety of programmed cell death 1 (PD-1) and programmed cell death 1 ligand (PD-L1) inhibitors using a meta-analysis of present trials for advanced melanoma. A fully recursive literature search of the primary electronic databases for available trials was performed. The objective response rate (ORR) and the median progression-free survival (PFS) of clinical responses were considered the main endpoints to evaluate the efficacy, whereas Grade 3-4 adverse effects (AEs) were analyzed to evaluate safety. The ORR of PD-1 and PD-L1 inhibitors was 30% (95% CI: 25-35%). No significant difference in the ORR was observed after the comparisons of low-dose, median-dose, and high-dose cohorts. In addition, the rate of Grade 3-4 AEs was 9% (95% CI: 6-12%). According to the 3 randomized controlled trials that compared PD-1 inhibitors with chemotherapy, the difference between these 2 groups was found to be statistically significant with respect to the ORR, PFS and the incidence of Grade 3-4 AEs; that is, the relative risk (RR) of the ORR was 3.42 (95% CI: 2.49-4.69, P < 0.001), the hazard ratio (HR) of the PFS was 0.50 (95% CI: 0.44-0.58, P < 0.001), and the RR of Grade 3-4 AEs was 0.45 (95% CI: 0.31-0.65, P < 0.001). According to a meta-analysis of limited concurrent studies, PD-1 and PD-L1 inhibitors appear to be associated with improved response rates, superior response durability and tolerable toxicity in patients with advanced melanoma.
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http://dx.doi.org/10.1097/MD.0000000000003134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839950PMC
March 2016

The Clinical Characteristics of Neonatal Sepsis Infection in Southwest China.

Intern Med 2016 15;55(6):597-603. Epub 2016 Mar 15.

Microbiology Teaching and Research Section, West China School of Preclinical and Forensic Medicine, Sichuan University, China.

Objective: To identify the pathogens responsible for neonatal sepsis in a high-volume women and children's hospital in Southwest China.

Methods: We retrospectively studied 133 neonates who were admitted to the West China Women and Children's Hospital between 2008 and 2012 for sepsis. The clinical characteristics of the patients were recorded, and the antibiotic sensitivities of the isolated bacteria were determined.

Results: All of the included patients had clinical symptoms of sepsis, and subsequent blood cultures confirmed the infection. Almost 80% of patients were infected with coagulase-negative staphylococci (52.8%), Escherichia coli (23.6%), Klebsiella pneumoniae (16.0%) or Staphylococcus aureus (7.5%). Neonates who were infected with gram-negative bacteria, particularly K. pneumoniae, had lower birth weights and were admitted to hospital within 24 hours of birth. Additionally, 87.5% of the isolated K. pneumoniae strains were resistant to third generation cephalosporins.

Conclusion: Coagulase-negative staphylococci were the most common pathogens found in neonatal sepsis. Moreover, neonatal sepsis caused by gram-negative bacteria was more often observed in newborns of low birth weight. The isolated strains of gram-negative bacteria were highly resistant to cephalosporins. This observation highlights the issue of antibiotic-resistant pathogens in the clinical setting, which poses an added risk to infants presenting with sepsis.
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http://dx.doi.org/10.2169/internalmedicine.55.3930DOI Listing
September 2016

Adoptive immunotherapy combined chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.

Anticancer Drugs 2016 Jun;27(5):433-8

aState Key Laboratory of Molecular Oncology, Cancer Hospital bDepartment of Medical Oncology, Cancer Institute/Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

The aim of this study was to compare the efficacies between adoptive immunotherapy combined chemoradiotherapy and chemoradiotherapy alone in patients with non-small-cell lung cancer (NSCLC). The databases PubMed, EMBASE, and Cochrane database were searched to identify eligible clinical trials. Data analyses were carried out using a comprehensive meta-analysis program, version 2 software. A total of seven articles were finally included in the analysis. Meta-analyses showed that compared with chemoradiotherapy alone, adoptive immunotherapy combined with chemoradiotherapy could improve the 2-year overall survival [odds ratio (OR)=2.45, 95% confidence interval (CI): 1.60-3.75, P<0.001], but not 2-year progression-free survival (OR=1.81, 95% CI: 0.61-5.36, P=0.284). Specifically, early (OR=3.32, 95% CI: 1.38-7.95, P<0.01) but not advanced (OR=3.75, 95% CI: 0.96-14.68, P=0.057) NSCLC patients were likely to gain a large benefit from the adoptive immunotherapy. Most of the adoptive immunotherapy-induced adverse effects were self-limited, mainly including fever, shiver, nausea, fatigue, etc. and severe toxicities were not observed. Adoptive immunotherapy combined with chemoradiotherapy can delay the recurrence of NSCLC and improve survival in patients, where the benefits are even more significant in patients with early-stage NSCLC.
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http://dx.doi.org/10.1097/CAD.0000000000000346DOI Listing
June 2016