Publications by authors named "Yuchen Jiang"

34 Publications

The novel RET inhibitor SYHA1815 inhibits RET-driven cancers and overcomes gatekeeper mutations by inducing G1 cell cycle arrest through c-Myc downregulation.

Mol Cancer Ther 2021 Sep 13. Epub 2021 Sep 13.

Anti-tumor Pharmacology, Shanghai Institute of Material Medica

Rearranged during transfection, an oncogenic driver, has been found in multiple tumor types and is thus a promising anticancer therapeutic target. Novel selective RET inhibitors (RETis) that can overcome V804 gatekeeper mutations, endowing resistance to multikinase inhibitors (MKIs) and, in particular, achieving KDR selectivity, are needed. In addition, the mechanisms underlying RET inhibition-induced antiproliferative effects in the context of RET addiction are incompletely understood. This study describes a novel, selective RETi, SYHA1815, which inhibited the kinase activity of RET wildtype and V804 mutant with a IC50 in the subnanomolar to nanomolar range. Notably, SYHA1815 exhibited approximately 20-fold selectivity for RET over KDR, almost equivalent to that of the launched selective inhibitor pralsetinib. SYHA1815 had only a marginal inhibitory effect on cellular KDR signaling at a high (200 nM) concentration, confirming the selectivity over KDR. In addition, SYHA1815 exhibited a favorable selectivity profile, with greater than 100-fold selectivity for RET over 347 other kinases. It exhibited potent antitumor efficacy and overcame V804 mutations in vitro and in vivo by targeting RET. Then, using SYHA1815 as a probe, we found that RET inhibition suppressed RET-driven cell proliferation via G1 cell cycle arrest through downregulating Myc. Furthermore, disruption of c-Myc upon Brd4 inhibitor treatment led to G1 cell cycle arrest and overrode RET-driven cell proliferation. Moreover, consistent with the marked in vivo efficacy of RET inhibition, the intratumoral c-Myc level was significantly decreased. In summary, SYHA1815 is a promising RETi for RET-aberrant cancer treatment that is currently in a phase I trial.
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http://dx.doi.org/10.1158/1535-7163.MCT-21-0127DOI Listing
September 2021

Industrial applications of digital twins.

Philos Trans A Math Phys Eng Sci 2021 Oct 16;379(2207):20200360. Epub 2021 Aug 16.

Department of Electrical and Electronics Engineering, Bogazici University, 34342 Istanbul, Turkey.

A digital twin (DT) is classically defined as the virtual replica of a real-world product, system, being, communities, even cities that are continuously updated with data from its physical counterpart, as well as its environment. It bridges the virtual cyberspace with the physical entities and, as such, is considered to be the pillar of Industry 4.0 and the innovation backbone of the future. A DT is created and used throughout the whole life cycle of the entity it replicates, from cradle to grave, so to speak. This article focuses on the present state of the art of DTs, concentrating on the use of DTs in industry in the context of smart manufacturing, especially from the point of view of plantwide optimization. The main capabilities of DTs (mirroring, shadowing and threading) are discussed in this context. The article concludes with a perspective on the future. This article is part of the theme issue 'Towards symbiotic autonomous systems'.
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http://dx.doi.org/10.1098/rsta.2020.0360DOI Listing
October 2021

In-situ ZnO template preparation of coal tar pitch-based porous carbon-sheet microsphere for supercapacitor.

J Colloid Interface Sci 2021 Nov 9;602:721-731. Epub 2021 Jun 9.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education of China, Key Laboratory of Chemical Engineering Processes & Technology for High-efficiency Conversion (College of Heilongjiang Province), School of Chemistry and Material Science, Heilongjiang University, Harbin 150080, China. Electronic address:

Three-dimension (3D) porous carbon-sheet microspheres (PCSMs) are prepared through coating coal tar pitch on basic zinc carbonate microspheres followed by in situ ZnO template carbonization and KOH activation. The as-prepared PCSMs show microsphere morphology composed of petal-like carbon nanosheets, which have large specific area (1359.88-2059.43 m g) and multiscale pores (mainly micropores and mesopores). As the supercapacitor electrodes, the 3D PCSMs present a good electrochemical performance with a large specific capacitance of 313 F g at 1 A g and high rate capability of 81.9% capacitance retention when increasing the current density up to 50 A g in a three-electrode system. In addition, the energy density can reach up to 18.79 Wh kg at a high power density of 878.4 W kg for PCSMs-0.2a symmetrical supercapcitor in 1 M NaSO electrolyte.
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http://dx.doi.org/10.1016/j.jcis.2021.06.037DOI Listing
November 2021

Environmental Efficiency Assessment of Heavy Pollution Industry by Data Envelopment Analysis and Malmquist Index Analysis: Empirical Evidence from China.

Int J Environ Res Public Health 2021 05 27;18(11). Epub 2021 May 27.

School of Business, Jiangsu Normal University, Xuzhou 221116, China.

Industrial waste discharged by heavy pollution industry is one of the main causes of global environmental degradation. Research on the environmental efficiency of high-polluting industry is necessary to tackle the problem of global environmental pollution. Using panel data of 19 sub-industries in China's heavy pollution industry from 2001 to 2015, this article employs Data Envelopment Analysis (DEA) and Malmquist index (MI) to measure the environmental efficiency of heavy pollution industry from both the dynamic and static perspectives. The results show that the environmental efficiency of China's heavy pollution industry maintains an upward trend but did not reach the optimal level. The general trend shows a phased trend of increasing first and then decreasing. Besides, there are inter-industry differences in the environmental efficiency across the examined sub-industries. Based on the research findings, this article proposes a set of corresponding countermeasures to solve the global pollution problem, such as reducing energy inputs and minimizing the volumes of the main categories of emissions in high-polluting industry, as well as improving the production management in the group of high environmental efficiency and strengthening technical capabilities in the group of low environmental efficiency.
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http://dx.doi.org/10.3390/ijerph18115761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198010PMC
May 2021

Multiresponsive Cellulose Nanocrystal Cross-Linked Copolymer Hydrogels for the Controlled Release of Dyes and Drugs.

Polymers (Basel) 2021 Apr 9;13(8). Epub 2021 Apr 9.

Key Laboratory of Fine Chemicals in Universities of Shandong, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.

Multiresponsive hydrogels have attracted tremendous interest due to their promising applications in tissue engineering, wearable devices, and flexible electronics. In this work, we report a multiresponsive upper critical solution temperature (UCST) composite hydrogel based on poly (acrylic acid-co-acrylamide), PAAc-co-PAAm, sequentially cross-linked by acid-hydrolysis cellulose nanocrystals (CNCs). Scanning electron microscopy (SEM) observations demonstrated that the hydrogels are formed by densely cross-linked porous structures. The PAAc/PAAm/CNC hybrid hydrogels exhibit swelling and shrinking properties that can be induced by multiple stimuli, including temperature, pH, and salt concentration. The driving force of the volume transition is the formation and dissociation of hydrogen bonds in the hydrogels. A certain content of CNCs can greatly enhance the shrinkage capability and mechanical strength of the hybrid hydrogels, but an excess addition may impair the contractility of the hydrogel. Furthermore, the hydrogels can be used as a matrix to adsorb dyes, such as methylene blue (MB), for water purification. MB may be partly discharged from hydrogels by saline solutions, especially by those with high ionic strength. Notably, through temperature-controlled hydrogel swelling and shrinking, doxorubicin hydrochloride (DOX-HCl) can be controllably adsorbed and released from the prepared hydrogels.
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http://dx.doi.org/10.3390/polym13081219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070268PMC
April 2021

Delayed Post-Operative Subcutaneous Emphysema.

Cureus 2021 Feb 1;13(2):e13051. Epub 2021 Feb 1.

Otolaryngology - Head and Neck Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, GBR.

The authors present the case of an 87-year-old woman who developed a delayed onset of subcutaneous emphysema post-operatively. We discuss the causative factors - in this case, presumed injury to her hypo-pharynx during a reportedly uneventful endotracheal intubation, the investigations and the management of this rare complication.
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http://dx.doi.org/10.7759/cureus.13051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925055PMC
February 2021

Anionic Biopolymer Assisted Preparation of [email protected] Heterostructure Nanoparticles with Oxygen Vacancies for Ambient Electrocatalytic Ammonia Synthesis.

Inorg Chem 2021 Mar 5;60(6):4116-4123. Epub 2021 Mar 5.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education of China. Key Laboratory of Chemical Engineering Processes & Technology for High- efficiency Conversion (College of Heilongjiang Province), School of Chemistry and Material Science. Heilongjiang University, Harbin 150080, China.

Recently, Mo-based metal catalysts are widely applied in the electrocatalytic nitrogen reduction reaction (NRR) due to the lower binding energy between the Mo atom and N atom. The design of a Mo-based [email protected] heterostructure and the introduction of anion vacancies are effective measures to improve their NRR performance. In this research, the cross-linked [email protected] (Vo means oxygen vacancies) heterostructure nanoparticles with rich oxygen vacancies are first synthesized via pectin assisted hydrothermal reaction followed by calcination and treating with NaBH solution. [email protected] exhibits good electrocatalytic NRR performance with an ammonia yield rate of 9.75 μg h mg at -0.5 V (RHE) and a Faraday efficiency (FE) of 3.24% at -0.3 V (RHE) under ambient conditions.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00218DOI Listing
March 2021

The functions of autophagy at the tumour-immune interface.

J Cell Mol Med 2021 03 18;25(5):2333-2341. Epub 2021 Feb 18.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Autophagy is frequently induced in the hypoxic tumour microenvironment. Accumulating evidence reveals important functions of autophagy at the tumour-immune interface. Herein, we propose an update on the roles of autophagy in modulating tumour immunity. Autophagy promotes adaptive resistance of established tumours to the cytotoxic effects of natural killer cells (NKs), macrophages and effector T cells. Increased autophagic flux in tumours dampen their immunogenicity and inhibits the expansion of cytotoxic T lymphocytes (CTLs) by suppressing the activation of STING type I interferon signalling (IFN-I) innate immune sensing pathway. Autophagy in suppressive tumour-infiltrating immune subsets maintains their survival through metabolic remodelling. On the other hand, autophagy is involved in the antigen processing and presentation process, which is essential for anti-tumour immune responses. Genetic deletion of autophagy induces spontaneous tumours in some models. Thus, the role of autophagy is context-dependent. In summary, our review has revealed the dichotomous roles of autophagy in modulating tumour immunity. Broad targeting of autophagy may not yield maximal benefits. The characterization of specific genes regulating tumour immunogenicity and innovation in targeted delivery of autophagy inhibitors into certain tumours are among the most urgent tasks to sensitize cold cancers to immunotherapy.
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http://dx.doi.org/10.1111/jcmm.16331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933948PMC
March 2021

Transcriptome comparison of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients.

J Cosmet Dermatol 2021 Aug 22;20(8):2619-2626. Epub 2020 Dec 22.

Department of Dermatovenereology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Background: Oral isotretinoin is the first-line treatment of severe nodular acne. However, patients presenting ineffective or poor effective to oral isotretinoin are still a clinical problem, and its molecular genetic mechanisms remain unclear.

Aims: To compare the transcriptome profiles of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients and analyze the potential physiological roles to better understand the mechanisms of isotretinoin efficacy differences.

Patients/methods: Peripheral blood of 43 patients with severe acne was collected before treatment. After 8-week isotretinoin, patients presented effective and ineffective to isotretinoin treatment were selected and their pretreatment peripheral blood was analyzed. High-throughput sequencing was used to detect gene expression profiles. Gene Ontology and KEGG were used to perform functional annotation and pathway enrichment analysis.

Results: Ten acne patients (3 male and 7 female, age 31 ± 9.2) presented effectiveness by oral isotretinoin and 10 acne patients (4 male and 6 female, age 28 ± 7.7) presented ineffectiveness were included. Comparison of gene profiles of isotretinoin-effective and isotretinoin-ineffective patients revealed 2779 differentially expressed genes: 2723 upregulated and 56 downregulated. Differentially expressed genes were enriched in RNA degradation pathway, autophagy pathway, protein ubiquitination pathway, protein processing in endoplasmic reticulum pathway, T-cell receptor signaling pathway, spliceosome pathway, mRNA surveillance pathway, cell cycle pathway, long-term potentiation pathway, and FoxO signaling pathway.

Conclusion: Transcriptome expression differences not only participated in the acne pathogenesis, but also influenced the isotretinoin therapeutic effects. These findings might provide some evidence for exploring individualized therapy for acne patients.
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http://dx.doi.org/10.1111/jocd.13898DOI Listing
August 2021

Generation and molecular characteristics of a highly attenuated GPV strain through adaptation in GEF cells.

BMC Vet Res 2020 Nov 23;16(1):456. Epub 2020 Nov 23.

Key Laboratory of Jiangsu Preventive Veterinary Medicine, Key Laboratory for Avian Preventive Medicine, Ministry of Education, College of Veterinary Medicine, Yangzhou University, No.12 East Wenhui Road, Yangzhou, 225009, Jiangsu, China.

Background: Goose parvoviruses (GPVs) spread globally and cause a huge economic loss to the poultry industry. Although the attenuated GPV vaccines play a key role in preventing the disease caused by GPV, the molecular basis for the attenuation of GPV is barely known.

Results: A highly attenuated GPV strain, GPV-CZM-142, was generated through blindly passaging of the highly pathogenic strain, GPV-CZM, in goose embryonic fibroblasts (GEF) for 142 generations. The GEF-adapted GPV strain's virulence was 10,000 times weaker than its wild type counterpart, GPV-CZM, based on the ELD (50% Embryo Lethal Dose). By comparing with the wild type strain, genome sequencing analysis identified adapted mutations either in ITR or in NS and VP1 of GPV-CZM-142.

Conclusions: The highly attenuated GPV strain, GPV-CZM-142, provides a GPV vaccine candidate, and the identified virulence-related mutations give a novel insight into the molecular determinants of GPV virulence.
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http://dx.doi.org/10.1186/s12917-020-02673-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685651PMC
November 2020

Altered Gene Expression in Acne Vulgaris Patients Treated by Oral Isotretinoin: A Preliminary Study.

Pharmgenomics Pers Med 2020 15;13:385-395. Epub 2020 Sep 15.

Department of Dermato-Venereology, Third Affiliated Hospital of Sun-Yat sen University, Guangzhou, Guangdong, People's Republic of China.

Background/objective: The role of gene expression changes in acne patients treated by oral isotretinoin (ISO) and in influencing the ISO therapeutic effects is still unclear. In this study, we investigated the gene profiles of patients with severe acne who responded variously to ISO therapy.

Methods: The peripheral blood of 113 acne vulgaris patients (Pillsbury IV grade) was collected before treatment. After 8 weeks of oral ISO, nine acne patients were selected and divided into the following groups. A: effectively treated by ISO, group B: ineffectively treated by ISO, group C: ISO-induced acne flare-up, and 3 healthy subjects were included as control group D. The peripheral blood of patients pre- and post-treatment was subjected to high-throughput RNA sequencing technology and bioinformatics analysis of the separate groups (n = 3). The candidate genes were validated by qRT-PCR.

Results: Comparing pre- and post-oral ISO treatment, gene expression was changed as 39 genes in ISO-effective group, 345 genes in ISO-ineffective group, and 57 genes in ISO-induced acne flare-up group. Comparing the ISO-induced acne flare-up group with healthy control subjects revealed 34 upregulated genes and 23 downregulated genes, while comparing the ISO-induced acne flare-up group with ISO-ineffective patients identified 1835 changed genes. Expression of (2.73 fold, P=0.024512), (35.87 folds, P=0.038073), and (2.48 folds, P=0.004681) increased in the ISO-induced acne flare-up patients. Meanwhile, the expression of (0.18 fold, P=0.041934), (0.14 fold, P=0.030767), (0.41 fold, P=0.013383), and (0.00018 fold, P=0.000986) decreased when compared with ISO-ineffective patients.

Conclusion: Oral ISO treatment could temporarily alter gene expression in acne patients. ISO therapeutic mechanisms were involved, not only in regulating the inflammatory reaction but also in the process of DNA repair. , and might be susceptible to genes that could participate in the ISO-induced aggravation of acne.
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http://dx.doi.org/10.2147/PGPM.S250969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509477PMC
September 2020

The imidazopyridine derivative X22 prevents diabetic kidney dysfunction through inactivating NF-κB signaling.

Biochem Biophys Res Commun 2020 05 11;525(4):877-882. Epub 2020 Mar 11.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address:

Diabetic kidney disease (DKD) is considered a chronic inflammatory renal disease induced by hyperglycemia. Therefore, even meticulous control of blood glucose levels cannot prevent the progression of DKD efficiently. Management of the inflammatory response could be one of the most promising strategies for treatment. We previously validated an imidazopyridine derivative (X22) as an active compound in suppressing lipopolysaccharide-induced inflammation. However, its potential for protection against DKD has not been exanimated. In the present study, streptozotocin-induced type 1 diabetic mice were used to study the effect of X22 on DKD associated inflammation and fibrosis by Q-PCR and immunoblotting assays. The results showed that X22 significantly inhibited the production of inflammatory cytokines (IL-6, TNF-α) and fibrosis biomarkers. At the same time, kidney function was dramatically improved. To elucidate the mechanism of action of X22, we examined its effects on the NRK-52E cell line. Strikingly, X22 restored the protein level of IKB-α and blocked the nuclear translocation of P65. Collectively, the data indicate that X22 can attenuate diabetic kidney dysfunction and inflammatory injury and may represent a potential agent for the treatment of DKD. It could be a potential agent for use in the treatment of DKD.
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http://dx.doi.org/10.1016/j.bbrc.2020.03.016DOI Listing
May 2020

ARNS: Adaptive Relay-Node Selection Method for Message Broadcasting in the Internet of Vehicles.

Sensors (Basel) 2020 Feb 29;20(5). Epub 2020 Feb 29.

Department of Computer Science and Engineering, University of Texas at Arlington, Arlington, TX 76019, USA.

The proper utilization of road information can improve the performance of relay-node selection methods. However, the existing schemes are only applicable to a specific road structure, and this limits their application in real-world scenarios where mostly more than one road structure exists in the Region of Interest (RoI), even in the communication range of a sender. In this paper, we propose an adaptive relay-node selection (ARNS) method based on the exponential partition to implement message broadcasting in complex scenarios. First, we improved a relay-node selection method in the curved road scenarios through the re-definition of the optimal position considering the distribution of the obstacles. Then, we proposed a criterion of classifying road structures based on their broadcast characteristics. Finally, ARNS is designed to adaptively apply the appropriate relay-node selection method based on the exponential partition in realistic scenarios. Simulation results on a real-world map show that the end-to-end broadcast delay of ARNS is reduced by at least 13.8% compared to the beacon-based relay-node selection method, and at least 14.0% compared to the trinary partitioned black-burst-based broadcast protocol (3P3B)-based relay-node selection method. The broadcast coverage is increased by 3.6-7% in curved road scenarios, with obstacles benefitting from the consideration of the distribution of obstacles. Moreover, ARNS achieves a higher and more stable packet delivery ratio (PDR) than existing methods profiting from the adaptive selection mechanism.
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http://dx.doi.org/10.3390/s20051338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085589PMC
February 2020

Enhanced cardiomyocyte reactive oxygen species signaling promotes ibrutinib-induced atrial fibrillation.

Redox Biol 2020 02 20;30:101432. Epub 2020 Jan 20.

Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. Electronic address:

Atrial fibrillation (AF) occurs in up to 11% of cancer patients treated with ibrutinib. The pathophysiology of ibrutinib promoted AF is complicated, as there are multiple interactions involved; the detailed molecular mechanisms underlying this are still unclear. Here, we aimed to determine the electrophysiological and molecular mechanisms of burst-pacing-induced AF in ibrutinib-treated mice. The results indicated differentially expressed proteins in ibrutinib-treated mice, identified through proteomic analysis, were found to play a role in oxidative stress-related pathways. Finally, treatment with an inhibitor of NADPH oxidase (NOX) prevented and reversed AF development in ibrutinib-treated mice. It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-β protein expression. It was interesting that ibrutinib group also significantly increased the expression of ox-CaMKII, p-CaMKII (Thr-286) and p-RyR2 (Ser2814), causing enhanced abnormal sarcoplasmic reticulum (SR) Ca release and mitochondrial structures, as well as atrial fibrosis and atrial hypertrophy in ibrutinib-treated mice, and apocynin reduced the expression of these proteins. Ibrutinib-treated mice were also more likely to develop AF, and AF occurred over longer periods. In conclusion, our study has established a pathophysiological role for ROS signaling in atrial cardiomyocytes, and it may be that ox-CaMKII and p-CaMKII (Thr-286) are activated by ROS to increase AF susceptibility following ibrutinib treatment. We have also identified the inhibition of NOX as a potential novel AF therapy approach.
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http://dx.doi.org/10.1016/j.redox.2020.101432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994714PMC
February 2020

Preclinical evaluation of 3D185, a novel potent inhibitor of FGFR1/2/3 and CSF-1R, in FGFR-dependent and macrophage-dominant cancer models.

J Exp Clin Cancer Res 2019 Aug 22;38(1):372. Epub 2019 Aug 22.

Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Chinese Academy of Sciences, Shanghai Institute of Materia Medica, No. 555 Zuchongzhi Road, Pudong New District, Shanghai, 201203, People's Republic of China.

Background: The interaction between tumor cells and their immunosuppressive microenvironment promotes tumor progression and drug resistance. Thus, simultaneously targeting tumor cells and stromal cells is expected to have synergistic antitumor effects. Herein, we present for the first time a preclinical antitumor investigation of 3D185, a novel dual inhibitor targeting FGFRs, which are oncogenic drivers, and CSF-1R, which is the major survival factor for protumor macrophages.

Methods: The antitumor characteristics of 3D185 were assessed by a range of assays, including kinase profiling, cell viability, cell migration, immunoblotting, CD8 T cell suppression, and in vivo antitumor efficacy, followed by flow cytometric and immunohistochemical analyses of tumor-infiltrating immune cells and endothelial cells in nude mice and immune-competent mice.

Results: 3D185 significantly inhibited the kinase activity of FGFR1/2/3 and CSF-1R, with equal potency and high selectivity over other kinases. 3D185 suppressed FGFR signaling and tumor cell growth in FGFR-driven models both in vitro and in vivo. In addition, 3D185 could inhibit the survival and M2-like polarization of macrophages, reversing the immunosuppressive effect of macrophages on CD8 T cells as well as CSF1-differentiated macrophage induced-FGFR3-aberrant cancer cell migration. Furthermore, 3D185 inhibited tumor growth via remodeling the tumor microenvironment in TAM-dominated tumor models.

Conclusions: 3D185 is a promising antitumor candidate drug that simultaneously targets tumor cells and their immunosuppressive microenvironment and has therapeutic potential due to synergistic effects. Our study provides a solid foundation for the investigation of 3D185 in cancer patients, particularly in patients with aberrant FGFR and abundant macrophages, who respond poorly to classic pan-FGFRi treatment.
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http://dx.doi.org/10.1186/s13046-019-1357-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704710PMC
August 2019

Kaempferol reduces K63-linked polyubiquitination to inhibit nuclear factor-κB and inflammatory responses in acute lung injury in mice.

Toxicol Lett 2019 May 12;306:53-60. Epub 2019 Feb 12.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China; The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China. Electronic address:

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), pose a major clinical challenge. The major driving force in this syndrome is pulmonary inflammation. Recent studies have shown that the naturally occurring flavonoid kaempferol (KPF) reduces endotoxin-induced inflammatory responses in mice. However, the mechanisms of these anti-inflammatory activities are not currently known. Here, we show that enhanced inflammatory cytokine production in response to lipopolysaccharide (LPS) is due to increased TGF-β-activated kinase-1 (TAK1) phosphorylation with subsequent activation of nuclear factor-κB (NF-κB). KPF attenuates LPS-mediated production of cytokines as well as activation of NF-κB. Furthermore, we identified that KPF prevents increased K63-linked polyubiquitination on TNF receptor associated factor-6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1). K63-linked polyubiquitination is a signal leading to enhanced activation of downstream pathways including TAK1. Our study shows that KPF is effective in reducing lung damage induced by LPS by modulating TRAF6 polyubiquitination. Furthermore, our findings may provide novel molecular targets to alleviate acute lung injury.
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http://dx.doi.org/10.1016/j.toxlet.2019.02.005DOI Listing
May 2019

Discovery and optimization of a series of 3-substituted indazole derivatives as multi-target kinase inhibitors for the treatment of lung squamous cell carcinoma.

Eur J Med Chem 2019 Feb 7;163:671-689. Epub 2018 Dec 7.

Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, NO.19A Yuquan Road, Beijing, 100049, China. Electronic address:

Although lung adenocarcinoma patients have benefited from the development of targeted therapy, patients with lung squamous cell carcinoma (SqCC) have no effective treatment due to the complexity and heterogeneity of the disease. Therefore, basing on the genetic analysis of mutations in lung squamous cell carcinoma to design multi-target inhibitors represents a potential strategy for the medical treatment. In this study, through screening an in-house focused library, we identified an interesting indazole scaffold. And following with binding analysis, we elaborated the structure-activity relationship of this hit compound by optimizing four parts guided by the DDR2 enzymatic assay, which resulted in a potent lead compound 10a. We conducted further optimization of dual enzymatic inhibitions towards FGFR1 and DDR2, two important kinases in lung squamous cell carcinoma. Finally, from the cellular antiproliferative activity tests and in vivo pharmacokinetic test, 3-substituted indazole derivative 11k was found to be a promising candidate and subjected to in vivo pharmacology study with the mouse xenograft models, demonstrating profound anti-tumor efficacy. Additional in vitro druglike assessment reinforced that compound 11k could be valuable for SqCC drug development.
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http://dx.doi.org/10.1016/j.ejmech.2018.12.015DOI Listing
February 2019

IL-25 promotes Th2-type reactions and correlates with disease severity in the pathogenesis of oral lichen planus.

Arch Oral Biol 2019 Feb 17;98:115-121. Epub 2018 Nov 17.

Department of Oral Medicine, School of Stomatology, Capital Medical University, Beijing, China. Electronic address:

Objective: The aim of the present study was to investigate the correlation between IL-25 expression and disease severity, and the potential immunoregulatory role of IL-25 expression in oral lichen planus (OLP).

Materials And Methods: The oral mucosal tissue samples obtained from OLP patients and healthy controls (HCs) were analyzed for IL-25 expression by real-time quantitative PCR (qPCR) and immunohistochemistry. Recombinant IL-25 was used to stimulate OLP patient-derived CD4 + T cells, and then IL-4 secretion and mRNA expression were evaluated by ELISA and qPCR, respectively. The efficiency of the siRNA-mediated knockdown of IL-25R expression in oral keratinocytes was determined by qPCR and Western blotting. Human oral keratinocyte cells were cultured with the recombinant human cytokines IL-25, IL-17 A and IL-17 F. The production of associated cytokines by keratinocytes was determined by qPCR. Statistical analyses of quantitative data were performed using SPSS software.

Results: The IL-25 and IL-4 mRNA levels were elevated and correlated significantly with each other in specific OLP subtype lesions compared to HCs, while the numbers of IL-25 positive cells were also increased in local OLP lesions as compared to HCs. In vitro culture with recombinant IL-25 could significantly promote CD4 + T cells from both subtypes of OLP to produce IL-4 mRNA and remarkably elevate supernatant IL-4 levels in reticular OLP CD4 + T cell cultures, which may be attributed to the elevated expression of IL-25R in local OLP lesions. Statistical analyses demonstrated that the simultaneously increased levels of IL-4, CXCL8 and CCL20 in keratinocytes were induced by IL-25 but not IL-17 A or IL-17 F. Decreasing IL-25R subunit expression by siRNA-mediated knockdown significantly blocked the expression of all cytokine-produced inflammatory mediators in oral keratinocytes.

Conclusions: In OLP lesions, IL-25 can function to mediate the Th2 response in specific disease subtypes, which may be an important cause of OLP disease chronicity and persistent inflammation.
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http://dx.doi.org/10.1016/j.archoralbio.2018.11.015DOI Listing
February 2019

Comparison between three-dimensional CT and conventional radiography in proximal tibia morphology.

Medicine (Baltimore) 2018 Jul;97(30):e11632

Department of Orthopaedic Trauma, East Hospital, Tongji University School of Medicine, Shanhai, China.

To provide morphological parameters of the normal tibial plateau by using three-dimensional (3D) CT and conventional radiography.We performed morphological measurements of tibial plateau on 157 consecutive adults using radiographic and 3D computed tomography (CT). Gender differences as well as differences in measurement techniques were statistically compared. Intraclass correlation coefficient (ICC) was used to evaluate intra- and interobserver reproducibility.The mediolateral dimensions, anteroposterior dimensions of tibial plateau showed significant differences according to gender, but no statistical differences were observed in coronal tibial slope as well as in posterior slope. There were significant differences in all parameters between 2 measurement techniques. 3D-CT measurements had a higher ICC in all parameters than that in the radiographs.This study confirmed that 3D morphological measurements of tibial plateau have more reproducibility than radiographs. Our data will be helpful for tibial component design and placement.
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http://dx.doi.org/10.1097/MD.0000000000011632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078714PMC
July 2018

Computational biomechanical analysis of postoperative inferior tibiofibular syndesmosis: a modified modeling method.

Comput Methods Biomech Biomed Engin 2018 Apr 16;21(5):427-435. Epub 2018 Jul 16.

a Department of Orthopedic Trauma , East Hospital, Tongji University School of Medicine , Shanghai , China.

To analyze the biomechanical effect of syndesmotic screw through three and four cortices, a total of 12 finite element models simulating healthy ankles, tibiofibular syndesmosis injured ankles, and post-operative ankles by screw fixations through three or four cortices were built. A set of biomechanical data were obtained to find that screw fixation methods for inferior tibiofibular syndesmosis can help recover most of the biomechanical relations of the ankle especially the tricortical fixation, while the screw of quadricortical fixation bear more stress than the tricortical fixation. The modeling method for finite element models was also modified for saving more time and realizing personalized modeling for clinical application.
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http://dx.doi.org/10.1080/10255842.2018.1472770DOI Listing
April 2018

Assessment of Screw Length of Proximal Humerus Internal Locking System (PHILOS) Plate for Proximal Humeral Fractures Using Three-Dimensional Computed Tomography Scan.

Med Sci Monit 2018 Feb 25;24:1158-1165. Epub 2018 Feb 25.

Department of Orthopedic Trauma, East Hospital, Tongji University School of Medicine, Shanghai, China (mainland).

BACKGROUND Screw perforation and varus collapse are common complications of treatment with a PHILOS (proximal humerus internal locking system) plate for proximal humerus fractures, which are associated with improper screw length selection and lack of medial column support. The purposes of this study were: (1) to measure the proper length of periarticular screws of the PHILOS plate in the humeral head, and (2) to determine what factors influence the screw length and implantation of the inferomedial support screw. MATERIAL AND METHODS Computed tomography (CT) images of the normal proximal humerus in 134 cases were retrospectively reviewed. The length of periarticular screws was measured using three-dimensional (3D) techniques. Intraobserver and interobserver reliability of measurement were evaluated using intraclass correlation coefficients (ICCs). Sex and body height influences on screw length and implantation of the inferomedial screw were analyzed. RESULTS All measurements had excellent agreement (ICC>0.75). The screw length and implantation rate of the inferomedial screw were greater in males than in females. Positive correlations were observed between body height and screw length and implantation of the inferomedial screw (all P<0.001). CONCLUSIONS The screws were longer and the implantation rate was higher for inferomedial screws in males than in females, and were positively correlated with body height. Our data can be used as a reference for surgeons to reduce the number of times screws are changed intraoperatively and to reduce operation duration and minimize use of intraoperative fluoroscopy for proximal humerus fractures treated with the PHILOS plate.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836538PMC
http://dx.doi.org/10.12659/msm.906355DOI Listing
February 2018

Long non-coding RNA implicated in the invasion and metastasis of head and neck cancer: possible function and mechanisms.

Mol Cancer 2018 01 24;17(1):14. Epub 2018 Jan 24.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral Medicine of West China Hospital of Stomatology, Sichuan University, No. 14, Sec.3, Renminnan Road, Chengdu, Sichuan, 610041, China.

Head and neck cancer (HNC) ranks as the 6th most common malignancy across the world. Metastasis is a hallmark of cancer, primarily contributing to the relapse and poor prognosis of HNC. Recently, long noncoding RNAs (lncRNAs), previously considered as non-functional, are increasingly appreciated by scholars to play crucial roles in mediating HNC metastasis. LncRNAs, which are located in the nucleus and cytoplasm, mainly exert their function via epigenetic modification, transcriptional control and translational regulation. As several lncRNAs are presently demonstrated to participate in HNC metastasis, we make a summary of the functions and mechanisms regarding these lncRNAs. As shown in the literature, most lncRNAs appear to promote the metastasis of HNC. Hence, we primarily discuss the lncRNAs involved in enhancing metastasis. Additionally, more studies are needed to understand those lncRNAs without clear mechanisms. Furthermore, we introduced the upstream regulator for the aberrant expression of lncRNAs in HNC. Finally, we concisely addressed future research prospects of lncRNAs, particularly the interplay between lncRNAs and tumor immunity as well as lncRNA-targeted therapeutic techniques, and we introduced clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possibly transformative tool to study lncRNAs. Although lncRNA research is still in the initial stage, it holds great promise to be applied as a prognosticator of HNC and a therapeutic target to inhibit HNC metastasis, which could significantly enhance the outcome of HNC patients.
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http://dx.doi.org/10.1186/s12943-018-0763-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784721PMC
January 2018

Detection of Intra-Articular Screw Penetration of Proximal Humerus Fractures: Is Postoperative Computed Tomography the Necessary Imaging Modality?

Acad Radiol 2019 02 18;26(2):257-263. Epub 2017 Dec 18.

Department of Orthopedic Trauma, East Hospital, Tongji University School of Medicine, 150 Jimo Rd, 200120 Shanghai, China.

Rationale And Objective: Screw penetration is the common complication of proximal humerus fractures treated with locking plates. This study compared postoperative plain radiography to computed tomography (CT) for their abilities in determining screw penetration, and was to evaluate whether advanced imaging modalities (two-dimensional [2D] CT; three-dimensional [3D] CT) could increase surgeons' level of confidence regarding their diagnoses.

Materials And Methods: Two observers reviewed radiological images of 134 patients who sustained proximal humerus fractures treated with locking plates. The observers were asked to answer two questions: (1) Is there screw penetrating into glenohumeral joint for this patient (Yes/No)? and (2) On a scale from 0 to 10, how confident are you about this diagnosis: (0-10) (0 = not at all confident; 10 = very confident)? Three evaluations were performed: (1) plain radiography alone, (2) radiography and 2D CT 4 weeks later, and (3) radiography in combination with 2D and 3D CT after that. This process was then repeated for intraobserver analysis.

Results: CT obtained almost perfect interobserver and intraobserver agreement (0.818-0.961), which was higher than radiography (0.377-0.655). For incidence of screw penetration, the significant difference was found between radiographs and CT images (P< .0125), but not between 2D and 3D CT images (P > .05). For confidence of diagnosis, the differences between imaging modalities were significant (all P< .001).

Conclusions: We suggest that postoperative CT scans (especially 3D CT images) should be used to evaluate the intra-articular screw penetration of proximal humerus fractures, especially when surgeons have not enough confidence in determining screw penetration using radiography alone.
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http://dx.doi.org/10.1016/j.acra.2017.10.021DOI Listing
February 2019

LRP6 is identified as a potential prognostic marker for oral squamous cell carcinoma via MALDI-IMS.

Cell Death Dis 2017 09 7;8(9):e3035. Epub 2017 Sep 7.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide, with 500 000 new cases each year. However, the mechanisms underlying OSCC development are relatively unknown. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was used to profile the differentially expressed peptides/proteins between OSCC tissues and their adjacent noncancerous tissues. Sixty-seven unique peptide peaks and five distinct proteins were identified with changed expression levels. Among them, LRP6 expression was found to be upregulated in OSCC tissues, and correlated with a cluster of clinicopathologic parameters, including smoking, drinking, tumor differentiation status, lymph node metastasis and survival time. Notably, knockdown of LRP6 inhibited the proliferation ability of OSCC cells. Furthermore, we demonstrated that the expression of LRP6 in OSCC cells is positively correlated with its downstream oncogene, FGF8. The present study suggests that LRP6 could be a potential biomarker for OSCC patients, and might further assist in the therapeutic decisions in OSCC treatment.
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http://dx.doi.org/10.1038/cddis.2017.433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636978PMC
September 2017

Post-operative radiological predictors of satisfying outcomes occurring after intra-articular calcaneal fractures: a three dimensional CT quantitative evaluation.

Int Orthop 2017 09 27;41(9):1945-1951. Epub 2017 Jul 27.

Department of Orthopaedic Trauma, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, China.

Purpose: No functional outcome related to 3-D CT evaluations for calcaneal fractures has been presented. The aims of this study are to analyze the post-operative morphological parameters of calcaneal fractures in 3-D space and to correlate the 3-D morphological parameters with functional outcomes.

Methods: Between 2009 and 2015, 156 patients operatively treated for displaced calcaneal fractures were retrospectively reviewed with an average follow-up time of 32.4 months. Böhler's angle, Gissane's angle, the length of calcaneal axis, the height of posterior facet, the length of posterior facet, and the subtalar joint congruity were evaluated post-operatively in accordance with 3-D CT. Each parameter was quantified, and then its association with the clinical outcomes assessed by the AOFAS score and Short Form-36 questionnaire was evaluated.

Results: The restoration of the length of calcaneal axis, the height of posterior facet, and the length of posterior facet had no significant correlation with the clinical outcomes (P > 0.05). The restoration of Böhler's angle and Gissane's angle had significant correlation with the better AOFAS score (P < 0.001), while no correlation was found with the SF-36 physical component summary score (P > 0.05). No significant association emerged between the clinical outcomes and reconstruction of the posterior facet congruity (P > 0.05).

Conclusion: The predictable functional outcome is related to the reconstruction of post-operative morphological characteristics of the calcaneus as evaluated on 3-D CT, especially the Böhler's angle and Gissane's angle. Despite post-operative step-off of the posterior facet exiting, the clinical outcomes appear to be not related to the posterior facet congruity.
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http://dx.doi.org/10.1007/s00264-017-3577-0DOI Listing
September 2017

Evaluation of computed tomography post-processing images in postoperative assessment of Lisfranc injuries compared with plain radiographs.

J Orthop Surg Res 2017 Jun 14;12(1):91. Epub 2017 Jun 14.

Department of Orthopaedic Trauma, East Hospital, Tongji University School of Medicine, 150 Jimo Road, 200120, Shanghai, China.

Background: The objective of this study is to evaluate the value of computed tomography (CT) post-processing images in postoperative assessment of Lisfranc injuries compared with plain radiographs.

Methods: A total of 79 cases with closed Lisfranc injuries that were treated with conventional open reduction and internal fixation from January 2010 to June 2016 were analyzed. Postoperative assessment was performed by two independent orthopedic surgeons with both plain radiographs and CT post-processing images. Inter- and intra-observer agreement were analyzed by kappa statistics while the differences between the two postoperative imaging assessments were assessed using the χ test (McNemar's test). Significance was assumed when p < 0.05.

Results: Inter- and intra-observer agreement of CT post-processing images was much higher than that of plain radiographs. Non-anatomic reduction was more easily identified in patients with injuries of Myerson classifications A, B1, B2, and C1 using CT post-processing images with overall groups (p < 0.05), and poor internal fixation was also more easily detected in patients with injuries of Myerson classifications A, B1, B2, and C2 using CT post-processing images with overall groups (p < 0.05).

Conclusions: CT post-processing images can be more reliable than plain radiographs in the postoperative assessment of reduction and implant placement for Lisfranc injuries.
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http://dx.doi.org/10.1186/s13018-017-0589-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471664PMC
June 2017

Preparation and antifouling properties of 2-(meth-acryloyloxy)ethyl cholinephosphate based polymers modified surface with different molecular architectures by ATRP.

Colloids Surf B Biointerfaces 2017 Aug 11;156:87-94. Epub 2017 May 11.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. Electronic address:

Choline phosphate (CP) containing polymers modified surfaces have been shown good resist to the adhesion of proteins while prompt the attaching of mammalian cells due to the dipole pairing between the CP groups of the polymer and the phosphorylcholine (PC) groups on the cell membrane. However, the antifouling activities of CP modified surface against microbes have not been investigated at present. In addition, CP containing polymers modified surface with different molecular architectures has not been prepared and studied. To this end, glass slides surface modified with two different 2-(meth-acryloyloxy)ethyl cholinephosphate (MCP) containing polymer (PMCP) structures, i.e. brush-like (Glass-PMCP) and bottle brush-like (Glass-PHEMA-g-PMCP) architectures, were prepared in this work by surface-initiated atom transfer radical polymerization (SI-ATRP). The surface physichemical and antifouling properties of the prepared surfaces were characterized and studied. The Glass-PMCP shows improved antifouling properties against proteins and bacteria as compared to pristine glass slides (Glass-OH) and glass slides grafted with poly(2-hydroxyethyl methacrylate) (Glass-PHEMA). Notably, a synergetic fouling resistant properties of PHEMA and PMCP is presented for Glass-PHEMA-g-PMCP, which shows superior antifouling activities over Glass-PHEMA and Glass-PMCP. Furthermore, glass slides containing PMCP, i.e. Glass-PMCP and Glas-PHEMA-g-PMCP, decrease platelet adhesion and prevent their activation significantly. Therefore, the combination of antifouling PHEMA and PMCP into one system holds potential for prevention of bacterial fouling and biomaterial-centered infections.
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http://dx.doi.org/10.1016/j.colsurfb.2017.05.030DOI Listing
August 2017

Morphometry of the Tibial Plateau at the Surface and Resected Levels.

J Arthroplasty 2017 08 8;32(8):2563-2567. Epub 2017 Mar 8.

Department of Orthopaedic Trauma, East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.

Background: We aim to make an anthropometric analysis of tibial plateau at the surface level and the resected level and analyze the correlation in lengths between 2 levels. We hypothesized that lengths at the surface level were longer than those at the resected level, which brought soft tissue tolerance for tibial component to overhang.

Methods: Anthropometric data were measured using three-dimensional structures reconstructed from tibial plateaus of 100 knees in 100 Chinese subjects (50 men and 50 women). Mediolateral, medial anteroposterior, and lateral anteroposterior lengths at the surface level and the resected level were measured, and the Pearson's correlation coefficients of these data were calculated.

Results: Mediolateral and medial anteroposterior lengths at the surface level were longer than those at the resected level by a mean 2.38 ± 1.29 and 1.99 ± 1.76 mm, respectively. Lateral anteroposterior length at the surface level was shorter than that at the resected level by a mean 1.54 ± 2.49 mm. All these differences between 2 levels had no gender difference.

Conclusion: Our findings suggest that tibial overhang could be better tolerated in the medial compared to the lateral compartment but this hypothesis has to be further investigated in a clinical study.
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http://dx.doi.org/10.1016/j.arth.2017.02.078DOI Listing
August 2017

MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell carcinoma arising from oral submucous fibrosis.

Oncotarget 2016 Sep;7(37):59987-60004

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.

Oral squamous cell carcinoma (OSCC) ranks among the most common cancer worldwide, and is associated with severe morbidity and high mortality. Oral submucous fibrosis (OSF), characterized by fibrosis of the mucosa of the upper digestive tract, is a pre-malignant lesion, but the molecular mechanisms underlying this malignant transformation remains to be elucidated. In this study, matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic strategy was employed to profile the differentially expressed peptides/proteins between OSCC tissues and the corresponding adjacent non-cancerous OSF tissues. Sixty-five unique peptide peaks and nine proteins were identified with altered expression levels. Of them, expression of NCOA7 was found to be up-regulated in OSCC tissues by immunohistochemistry staining and western blotting, and correlated with a pan of clinicopathologic parameters, including lesion site, tumor differentiation status and lymph node metastasis. Further, we show that overexpression of NCOA7 promotes OSCC cell proliferation in either in vitro or in vivo models. Mechanistic study demonstrates that NCOA7 induces OSCC cell proliferation probably by activating aryl hydrocarbon receptor (AHR). The present study suggests that NCOA7 is a potential biomarker for early diagnosis of OSF malignant transformation, and leads to a better understanding of the molecular mechanisms responsible for OSCC development.
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http://dx.doi.org/10.18632/oncotarget.11046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312364PMC
September 2016

Compared to X-ray, three-dimensional computed tomography measurement is a reproducible radiographic method for normal proximal humerus.

J Orthop Surg Res 2016 Jul 15;11(1):82. Epub 2016 Jul 15.

Department of Orthopaedic Trauma, East Hospital, Tongji University School of Medicine, 150 Jimo Road, 200120, Shanghai, China.

Background: Accurate comprehension of the normal humeral morphology is crucial for anatomical reconstruction in shoulder arthroplasty. However, traditional morphological measurements for humerus were mainly based on cadaver and radiography. The purpose of this study was to provide a series of precise and repeatable parameters of the normal proximal humerus for arthroplasty, based on the three-dimensional (3-D) measurements.

Methods: Radiographic and 3-D computed tomography (CT) measurements of the proximal humerus were performed in a sample of 120 consecutive adults. Sex differences, two image modalities differences, and correlations of the parameters were evaluated. Intra- and inter-observer reproducibility was evaluated using intraclass correlation coefficients (ICCs).

Results: In the male group, all parameters except the neck-shaft angle of humerus, based on 3-D CT images, were greater than those in the female group (P < 0.05). All variables were significantly different between two image modalities (P < 0.05). In 3-D CT measurement, all parameters expect neck-shaft angle had correlation with each other (P < 0.001), particularly between two diameters of the humeral head (r = 0.907). All parameters in the 3-D CT measurement had excellent reproducibility (ICC range, 0.878 to 0.936) that was higher than those in the radiographs (ICC range, 0.741 to 0.858).

Conclusions: The present study suggested that 3-D CT was more reproducible than plain radiography in the assessment of morphology of the normal proximal humerus. Therefore, this reproducible modality could be utilized in the preoperative planning. Our data could serve as an effective guideline for humeral component selection and improve the design of shoulder prosthesis.
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http://dx.doi.org/10.1186/s13018-016-0417-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947252PMC
July 2016
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