Publications by authors named "Yanying Chen"

12 Publications

  • Page 1 of 1

Progressive changes in the major salivary gland after radioiodine therapy for differentiated thyroid cancer: a single-center retrospective ultrasound cohort study.

Ultrasound Med Biol 2021 Jun 16. Epub 2021 Jun 16.

Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China 510282. Electronic address:

This study aimed to determine the prevalence of radioiodine-induced salivary gland damage by evaluating progressive changes in salivary glands using ultrasound. Four hundred forty-six patients with differentiated thyroid carcinoma who underwent total or near-total thyroidectomy and postoperative radioiodine therapy were retrospectively reviewed. From the first to the fifth follow-up visits, the positive rate of major salivary gland changes on ultrasound gradually increased from 2.0% to 33.0% (P<0.001) and possibly stabilized at the fifth visit (approximately 36 months). The first positive result was detected at an average of 20.78±8.72 months. Only 21 of the 161 positive cases eventually achieved negative ultrasound results (Fisher's test, P<0.001), and the 21 cases simply showed a coarse echotexure. In conclusion, ultrasound changes appeared late, and most of these changes were not reversed.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.05.013DOI Listing
June 2021

ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation.

Nat Commun 2021 04 20;12(1):2346. Epub 2021 Apr 20.

Department of Biochemistry and Research Center of Clinical Pharmacy of The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.

Cancer expression of PD-L1 suppresses anti-tumor immunity. PD-L1 has emerged as a remarkable therapeutic target. However, the regulation of PD-L1 degradation is not understood. Here, we identify several compounds as inducers of PD-L1 degradation using a high-throughput drug screen. We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. Overexpression of ARIH1 suppresses tumor growth and promotes cytotoxic T cell activation in wild-type, but not in immunocompromised mice, highlighting the role of ARIH1 in anti-tumor immunity. Moreover, combining EGFR inhibitor ES-072 with anti-CTLA4 immunotherapy results in an additive effect on both tumor growth and cytotoxic T cell activation. Our results delineate a mechanism of PD-L1 degradation and cancer escape from immunity via EGFR-GSK3α-ARIH1 signaling and suggest GSK3α and ARIH1 might be potential drug targets to boost anti-tumor immunity and enhance immunotherapies.
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http://dx.doi.org/10.1038/s41467-021-22467-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058344PMC
April 2021

Pharmacological targeting of MCL-1 promotes mitophagy and improves disease pathologies in an Alzheimer's disease mouse model.

Nat Commun 2020 11 12;11(1):5731. Epub 2020 Nov 12.

Department of Biochemistry & Molecular Medical Center, Zhejiang University School of Medicine, Hangzhou, 310058, China.

There is increasing evidence that inducing neuronal mitophagy can be used as a therapeutic intervention for Alzheimer's disease. Here, we screen a library of 2024 FDA-approved drugs or drug candidates, revealing UMI-77 as an unexpected mitophagy activator. UMI-77 is an established BH3-mimetic for MCL-1 and was developed to induce apoptosis in cancer cells. We found that at sub-lethal doses, UMI-77 potently induces mitophagy, independent of apoptosis. Our mechanistic studies discovered that MCL-1 is a mitophagy receptor and directly binds to LC3A. Finally, we found that UMI-77 can induce mitophagy in vivo and that it effectively reverses molecular and behavioral phenotypes in the APP/PS1 mouse model of Alzheimer's disease. Our findings shed light on the mechanisms of mitophagy, reveal that MCL-1 is a mitophagy receptor that can be targeted to induce mitophagy, and identify MCL-1 as a drug target for therapeutic intervention in Alzheimer's disease.
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http://dx.doi.org/10.1038/s41467-020-19547-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665171PMC
November 2020

BRAF V600E and lymph node metastases in papillary thyroid cancer.

Endocr Connect 2020 Oct;9(10):999-1008

Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, China.

Objective: To evaluate the relationship between the BRAF V600E mutation in lymph node metastasis (LNM) and its invasive characteristics in papillary thyroid cancer (PTC).

Material And Methods: A total of 373 PTC patients were enrolled in this study conducted at Zhujiang Hospital of Southern Medical University between January 2017 and December 2018. PTCs with cervical lymph node metastases were verified pathohistologically, and primary tumors and LNM were examined for the BRAF V600E mutation. Patients were excluded from the study if the BRAF V600E mutation was examined only in primary tumors or only in LNM.

Results: Of the 373 patients examined, BRAF V600E mutation frequency in primary tumors was slightly higher than in LNM (81.5% vs 78.0%, P = 0.000), the intra-class correlation coefficient (ICC) was 0.865 (95% CI 0.835-0.890). The BRAF V600E mutation in both primary tumor and LNM negatively correlated with the size of the largest metastatic focus of LNM (Odds ratio, OR = 0.297, 95% CI 0.143-0.616, P = 0.001; OR = 0.242, 95% CI 0.119-0.492, P = 0.000, respectively). There was no relationship between BRAF V600E mutation in LNM and the number, extranodal extension or stage of LNM (P > 0.05).

Conclusion: The BRAF V600E mutation in LNM may not be related to the invasive characteristics of LNM in PTC.
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http://dx.doi.org/10.1530/EC-20-0420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576641PMC
October 2020

Generation of cortical neurons through large-scale expanding neuroepithelial stem cell from human pluripotent stem cells.

Stem Cell Res Ther 2020 10 2;11(1):431. Epub 2020 Oct 2.

Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China.

Background: Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into cortical neurons for disease modeling and regenerative medicine. However, these procedures are hard to provide sufficient cells for their applications. Using a combination of small-molecules and growth factors, we previously identified one condition which can rapidly induce hPSCs into neuroepithelial stem cells (NESCs). Here, we developed a scalable suspension culture system, which largely yields high-quality NESC-spheres and subsequent cortical neurons.

Methods: The NESC medium was first optimized, and the suspension culture system was then enlarged from plates to stirred bioreactors for large-scale production of NESC-spheres by a stirring speed of 60 rpm. During the expansion, the quality of NESC-spheres was evaluated. The differentiation potential of NESC-spheres into cortical neurons was demonstrated by removing bFGF and two pathway inhibitors from the NESC medium. Cellular immunofluorescence staining, global transcriptome, and single-cell RNA sequencing analysis were used to identify the characteristics, identities, purities, or homogeneities of NESC-spheres or their differentiated cells, respectively.

Results: The optimized culture system is more conducive to large-scale suspension production of NESCs. These largely expanded NESC-spheres maintain unlimited self-renewal ability and NESC state by retaining their uniform sizes, high cell vitalities, and robust expansion abilities. After long-term expansion, NESC-spheres preserve high purity, homogeneity, and normal diploid karyotype. These expanded NESC-spheres on a large scale have strong differentiation potential and effectively produce mature cortical neurons.

Conclusions: We developed a serum-free, defined, and low-cost culture system for large-scale expansion of NESCs in stirred suspension bioreactors. The stable and controllable 3D system supports long-term expansion of high-quality and homogeneous NESC-spheres. These NESC-spheres can be used to efficiently give rise to cortical neurons for cell therapy, disease modeling, and drug screening in future.
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http://dx.doi.org/10.1186/s13287-020-01939-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532602PMC
October 2020

Postoperative thyroid remnants for differentiated thyroid cancer may not affect the outcome of high-dose radioiodine therapy.

Oral Oncol 2020 05 3;104:104610. Epub 2020 Mar 3.

Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, 253 Gongye Road, Guangzhou, Guangdong Province 510282, China. Electronic address:

Objectives: This study aims to provide a way to estimate the volume of the thyroid remnant and determine its relationship with the outcome of radioiodine (RAI) therapy in depth.

Materials And Methods: A retrospective analysis was performed on patients who underwent initial RAI therapy between January 2010 and January 2016. The patients were divided into five groups based on the thyroid remnant estimated by post-therapy whole-body scan(post-Rx WBS), thyroid scintigraphy and ultrasonography. The relationship between the volume of thyroid remnant and the outcome of RAI therapy were evaluated by univariate analysis and multivariate analysis.

Results: Of 703 patients, the majority could be found different size of thyroid remnants using the three imaging methods, and only few patients(2.1%) could reach no thyroid remnant. There was no association between the volume of thyroid remnant and the outcome of RAI therapy in univariate analysis (χ = 1.633, P = 0.652) and multivariate analysis (P > 0.05). In the subgroup of patients with high-risk factors, there was still no significant difference (intermediate risk subgroup: P = 0.338 vs high risk subgroup: P = 0.263).

Conclusion: Different sizes of thyroid remnants were left after surgery. However, in high radioiodine activity, the volume of thyroid remnants may not affect the outcome of RAI therapy even in patients with some high-risk factors, so the high radioiodine activities may resolve the the problem caused by thyroid remnants in some cases.
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http://dx.doi.org/10.1016/j.oraloncology.2020.104610DOI Listing
May 2020

[Congenital insensitivity to pain with anhidrosis: A case report and literature review].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2019 Oct;44(10):1203-1208

Emergency Center, Children's Hospital of Hunan Province, Changsha 410007, China.

To analyze the clinical manifestations and gene mutations in children with congenital insensitivity to pain with anhidrosis (CIPA), and review related literature. An infant diagnosed with congenital insensitivity to pain with anhidrosis was reported. The main clinical manifestations of the infant were painless, no sweat, and repeated fever. Peripheral blood of the infant and his parents was collected, and candidate variants were confirmed by Sanger sequencing. The results of molecular genetic analysis showed that there were compound heterozygous mutations (c.36G>A, c.851-33T>A) of neurotrophic tyrosine kinase receptor type 1 (NTRK1) in the infant. c.36G>A and c.851-33T>A were inherited from his father and mother, respectively. c.851-33T>A is a previously reported mutation, c.36G>A is an unreported mutation, which can lead to the tryptophan changing into a stop codon. According to the American College of Medical Genetics and Genomics (ACMG) variant interpretation guidelines, the mutation is interpreted as pathogenic, and the biological hazard is potentially harmful. Congenital insensitivity to pain with anhidrosis is a rare inherited disorder. Genetic molecular genetic analysis is helpful to diagnose and discover new gene mutations.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2019.190390DOI Listing
October 2019

Clinical significance of the BRAFV600E mutation in PTC and its effect on radioiodine therapy.

Endocr Connect 2019 Jun;8(6):754-763

Department of Nuclear Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, China.

The goal of this study was to explore the relationship of the BRAFV600E mutation with clinicopathologic factors and evaluate the effect of radioactive iodine (RAI) therapy in a large group of intermediate- and high-risk papillary thyroid cancer (PTC) patients with the BRAFV600E mutation and without distant metastases. We collected data for PTC patients who underwent total or near-total thyroidectomy and RAI treatment in our hospital from January 2014-December 2017. There were 1220 PTC patients who met the criteria, and the BRAFV600E mutation was observed in 979 of them (80.2%). Multivariate analysis identified that the BRAFV600E mutation remained independently associated with age at diagnosis, and bilaterality (OR = 1.023, 95% CI = 1.012-1.039, P < 0.001; OR = 1.685, 95% CI = 1.213-2.341, P = 0.002, respectively). In addition, the patients with bilateral PTCs had a higher prevalence of extrathyroid invasion, capsular invasion and fusion of metastatic lymph nodes than the unilateral PTC patients. The response to RAI therapy was evaluated in both the entire series and the patients with a high recurrence risk; no significant difference was discerned between the BRAFV600E mutation and the wild-type groups (P = 0.237 and P = 0.498, respectively). To summarize, our results confirmed that PTC patients with the BRAFV600E mutation exhibit more aggressive characteristics. In addition, the patients with bilateral PTC have a higher incidence of extrathyroid invasion. Moreover, BRAFV600E mutation PTC patients did not show a poorer clinical response after postsurgical RAI therapy, suggesting that RAI therapy may improve the general clinical outcome of these patients.
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http://dx.doi.org/10.1530/EC-19-0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547306PMC
June 2019

Novel B7-H4-mediated crosstalk between human non-Hodgkin lymphoma cells and tumor-associated macrophages leads to immune evasion via secretion of IL-6 and IL-10.

Cancer Immunol Immunother 2017 Jun 28;66(6):717-729. Epub 2017 Feb 28.

Department of Hematology, Linyi People's Hospital, Shandong University, No. 27 Jiefang Road, Lanshan District, Linyi, Shandong, China.

Non-Hodgkin lymphoma (NHL) is an incurable lymphoproliferative cancer, and patients with NHL have a poor prognosis. The present study explored the regulatory mechanism of expression and possible roles of the immunosuppressive B7-H4 molecule in human NHL. For functional studies, NHL-reactive T cell lines were generated via the isolation of allogeneic CD3 T cells from healthy donors and repeated in vitro stimulation with irradiated NHL cells isolated from patients. B7-H4 was found to be distributed in NHL cells and tissues, and its surface protein expression levels were further upregulated by the incubation of NHL cells with interleukin (IL)-6, IL-10, or interferon-γ. Additionally, the supernatants of tumor-associated macrophages (tMφs) upregulated B7-H4 surface expression by producing IL-6 and IL-10. B7-H4 expressed in NHL cells inhibited the cytotoxic activity of NHL-reactive T cells. Conversely, the inhibition of B7-H4 in NHL cells promoted T cell immunity and sensitized NHL cells to cytolysis. Furthermore, tMφs induced B7-H4 promoted NHL cell evasion of the T cell immune response. In conclusion, this study shows that NHL-expressed B7-H4 is an important immunosuppressive factor that inhibits host anti-tumor immunity to NHL. Targeting tumor-expressed B7-H4 may thus provide a new treatment strategy for NHL patients.
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http://dx.doi.org/10.1007/s00262-017-1961-7DOI Listing
June 2017

Effects of cardiopulmonary bypass on lung nuclear factor-kappa B activity, cytokine release, and pulmonary function in dogs.

Iran J Basic Med Sci 2015 Dec;18(12):1233-9

Department of Extracorporeal Circulation, the Affiliated Zhongshan Hospital of Fudan University, Shanghai 200032, China.

Objectives: To study the effect of cardiopulmonary bypass (CPB) on nuclear factor-kappa B (NF-κB) and cytokine expression and pulmonary function in dogs.

Materials And Methods: Twelve male mongrel dogs were divided into a methylprednisolone group (group M) and a control group (group C). All animals underwent aortic and right atrial catheterization under general anesthesia. Changes in pulmonary function and hemodynamics were monitored and the injured site was histologically evaluated.

Results: The activity of NF-κB and myeloperoxidase (MPO), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8, and the wet/dry (W/D) weight ratio were significantly higher after CPB than before CPB in both groups (P<0.01), with the lower values in group M than in group C, at different time points (P<0.01). Histological evaluation revealed neutrophilic infiltration and thickening of the alveolar interstitium in both groups; however, the degree of pathological changes was significantly lower in group M than in group C. The alveolar-arterial O2 tension difference (PA-aDO2) was significantly higher after CPB than before CBP (P<0.01), and lower in group M than in group C (P<0.01). The pulmonary compliance after removal of the aortic clamp obviously decreased in group C (P<0.05), with no significant change in group M.

Conclusion: CPB can significantly enhance the activation of NF-κB in lung tissues and increase the expression of inflammatory cytokines, thus inducing lung injury. Methylprednisolone can inhibit the NF-κB activation, thus inhibiting the release of cytokines and protecting the lung function.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744364PMC
December 2015

[Small hairpin RNA targeting inhibition of NF-κB gene in endometriosis therapy of Macaca fascicularis].

Zhonghua Fu Chan Ke Za Zhi 2015 Jan;50(1):48-53

Department of Obstetrics and Gynecology, Zhujiang Hospital of Southern Medical University, Guangzhou 510282, China.

Objective: To observe the therapeutic effect of NF-κB gene short hairpin RNA (shRNA) on endometriosis and identify the function of NF-κB on the maintenance and development of endometriosis in Macaca fascicularis.

Methods: The Macaca fascicularis model of endometriosis was developed, which divided into experimental group, negative control group and simple model group. The high specificity adenovirus vector mediated shRNA targeting NF-κB gene and negative control shRNA adenovirus with no-load NF-κB gene were synthesised. The experimental group injected the adenovirus which carried the NF-κB shRNA into the endometriosis lesions under laparoscopy surgery, the negative control group with no-load shRNA adenovirus and the simple models group injected with normal saline. Four weeks later after the injection, an observed operation was performed through laparoscopy and some lesions were collected. The CD34 immunohistochemistry of these lesions were done to detect the microvessel density, then the variation of the microvessel density among each group were observed. The expression of the NF-κB and proliferating cell nuclear antigen (PCNA) were detected through western blot.

Results: First, the Macaca fascicularis model of endometriosis was successful developed, and the experimental group has an evident atrophy in ectopic lesions compared with the previous. The lesions' microvessel density in experimental group decreased evidently compared with the negative control group and simple model group (0.002 0±0.000 3 versus 0.021 9±0.002 6 versus 0.024 5±0.003 3), and the differences was statistically significant (P < 0.01). The expression of PCNA (0.37±0.17 versus 0.57±0.26 versus 0.57±0.28) and NF-κB (0.338±0.174 versus 0.678±0.021 versus 0.645±0.098) in experiment group was lower than the negative control group and simple model group, the differences were statistically significant (all P < 0.01).

Conclusion: Through targeting suppressed the NF-κB gene expression by NF-κB shRNA, we can inhibit the development of endometriosis through reducing the ability of angiogenesis and cell proliferation of ectopic endometrial cells.
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January 2015

[Adenovirus vector-mediated short hairpin RNA targeting nuclear factor-κB suppresses proliferation of endometrial cells of Macaca fascicularis in vitro].

Nan Fang Yi Ke Da Xue Xue Bao 2015 Mar;35(3):390-6

Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.E-mail:

Objective: To assess the effect of a high specific adenovirus vector-mediated shRNA targeting nuclear factor-κB (NF-κB) on cell proliferation of the endometrium of Macaca fascicularis.

Methods: The adenoviral vector NF-κB-p65-shRNA and the empty vector were separately trasnfected in cultured endometrial cells of Macaca fascicularis. The changes in the expression of the target gene protein and apoptotic proteins, cell proliferation, and cell cycle distribution were observed after the transfection.

Results: Compared with the control cells, infection of the endometrial cells with the NF-κB-p65-shRNA adenovirus significantly increased the expression levels of apoptotic proteins, promoted apoptosis of the endometrial cells, and reduced the cells in division?stage.

Conclusions: NF-κB-p65 shRNA adenovirus can effectively promote apoptosis of endometrial cells and inhibit the proliferation of endometrial cells of Macaca fascicularis.
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March 2015
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