Publications by authors named "Deguang Kong"

30 Publications

  • Page 1 of 1

VEGF-C mediates tumor growth and metastasis through promoting EMT-epithelial breast cancer cell crosstalk.

Oncogene 2021 Feb 9;40(5):964-979. Epub 2020 Dec 9.

Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

It is well established that a subset of cells within primary breast cancers can undergo an epithelial-to-mesenchymal transition (EMT), although the role of EMT in metastasis remains controversial. We previously demonstrated that breast cancer cells that had undergone an oncogenic EMT could increase metastasis of neighboring cancer cells via non-canonical paracrine-mediated activation of GLI activity that is dependent on SIX1 expression in the EMT cancer cells. However, the mechanism by which these SIX1-expressing EMT cells activate GLI signaling remained unclear. In this study, we demonstrate a novel mechanism for activation of GLI-mediated signaling in epithelial breast tumor cells via EMT cell-induced production and secretion of VEGF-C. We show that VEGF-C, secreted by breast cancer cells that have undergone an EMT, promotes paracrine-mediated increases in proliferation, migration, and invasion of epithelial breast cancer cells, via non-canonical activation of GLI-signaling. We further show that the aggressive phenotypes, including metastasis, imparted by EMT cells on adjacent epithelial cancer cells can be disrupted by either inhibiting VEGF-C in EMT cells or by knocking down NRP2, a receptor which interacts with VEGF-C, in neighboring epithelial cancer cells. Interrogation of TCGA and GEO public datasets supports the relevance of this pathway in human breast cancer, demonstrating that VEGF-C strongly correlates with activation of Hedgehog signaling and EMT in the human disease. Our study suggests that the VEGF-C/NRP2/GLI axis is a novel and conserved paracrine means by which EMT cells enhance metastasis, and provides potential targets for therapeutic intervention in this heterogeneous disease.
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http://dx.doi.org/10.1038/s41388-020-01539-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867573PMC
February 2021

Co-transplantation with adipose-derived cells to improve parathyroid transplantation in a mice model.

Stem Cell Res Ther 2020 05 26;11(1):200. Epub 2020 May 26.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China.

Background: Accidentally removed parathyroid glands are still challenging in neck surgery, leading to hypoparathyroidism characterized with abnormally low levels of parathyroid hormone. Parathyroid auto-transplantation is usually applied in compensation. To improve the efficiency of parathyroid transplantation, we introduced a method by co-transplanting with adipose-derived cells, including stromal vascular fractions (SVFs) and adipose-derived stem cells (ADSCs), and investigated the underlying molecular mechanisms involved in parathyroid transplantation survival.

Methods: Rat and human parathyroid tissues were transplanted into nude mice as parathyroid transplantation model to examine the effects of SVFs and ADSCs on grafts angiogenesis and survival rates, including blood vessel assembly and parathyroid hormone levels. Several angiogenic factors, such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF) 2, were assessed in parathyroid grafts. The effects of hypoxia were investigated on ADSCs. The modulatory roles of the eyes absent homolog 1 (EYA1), which is vital in parathyroid development, was also investigated on angiogenic factor production and secretion by ADSCs. All experimental data were statistically processed. Student's t test was used to assess significant differences between 2 groups. For multiple comparisons with additional interventions, two-way ANOVA followed by Tukey's post hoc test was performed. P < 0.05 was considered as significant.

Results: SVFs improve rat parathyroid transplantation survival and blood vessel assembly, as well as FGF2 and VEGF-A expression levels in parathyroid transplantation mice. Functional human parathyroid grafts have higher microvessel density and increased VEGF-A expression. The supernatant of ADSCs induced tubule formation and migration of human endothelial cells in vitro. Hypoxia had no effect on proliferation and apoptosis of human ADSCs but induced higher angiogenic factor levels of VEGF-A and FGF2, modulated by EYA1, which was confirmed by parathyroid glands transplantation in mice.

Conclusions: Adipose-derived cells, including ADSCs and SVFs, improve parathyroid transplantation survival via promoting angiogenesis through EYA1-regulating angiogenetic factors in vitro and in vivo. Our studies proved an effective method to improve the parathyroid autotransplantation, which is promising for clinical patients with hypoparathyroidism when parathyroid glands were accidentally injured, removed, or devascularized.
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http://dx.doi.org/10.1186/s13287-020-01733-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249357PMC
May 2020

Cellular Plasticity in Breast Cancer Progression and Therapy.

Front Mol Biosci 2020 24;7:72. Epub 2020 Apr 24.

Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

With the exception of non-melanoma skin cancer, breast cancer is the most frequently diagnosed malignant disease among women, with the majority of mortality being attributable to metastatic disease. Thus, even with improved early screening and more targeted treatments which may enable better detection and control of early disease progression, metastatic disease remains a significant problem. While targeted therapies exist for breast cancer patients with particular subtypes of the disease (Her2+ and ER/PR+), even in these subtypes the therapies are often not efficacious once the patient's tumor metastasizes. Increases in stemness or epithelial-to-mesenchymal transition (EMT) in primary breast cancer cells lead to enhanced plasticity, enabling tumor progression, therapeutic resistance, and distant metastatic spread. Numerous signaling pathways, including MAPK, PI3K, STAT3, Wnt, Hedgehog, and Notch, amongst others, play a critical role in maintaining cell plasticity in breast cancer. Understanding the cellular and molecular mechanisms that regulate breast cancer cell plasticity is essential for understanding the biology of breast cancer progression and for developing novel and more effective therapeutic strategies for targeting metastatic disease. In this review we summarize relevant literature on mechanisms associated with breast cancer plasticity, tumor progression, and drug resistance.
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http://dx.doi.org/10.3389/fmolb.2020.00072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194153PMC
April 2020

Identification of a Small-Molecule Inhibitor That Disrupts the SIX1/EYA2 Complex, EMT, and Metastasis.

Cancer Res 2020 06 27;80(12):2689-2702. Epub 2020 Apr 27.

Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Metastasis is the major cause of mortality for patients with cancer, and dysregulation of developmental signaling pathways can significantly contribute to the metastatic process. The Sine oculis homeobox homolog 1 (SIX1)/eyes absent (EYA) transcriptional complex plays a critical role in the development of multiple organs and is typically downregulated after development is complete. In breast cancer, aberrant expression of SIX1 has been demonstrated to stimulate metastasis through activation of TGFβ signaling and subsequent induction of epithelial-mesenchymal transition (EMT). In addition, SIX1 can induce metastasis via non-cell autonomous means, including activation of GLI-signaling in neighboring tumor cells and activation of VEGFC-induced lymphangiogenesis. Thus, targeting SIX1 would be expected to inhibit metastasis while conferring limited side effects. However, transcription factors are notoriously difficult to target, and thus novel approaches to inhibit their action must be taken. Here we identified a novel small molecule compound, NCGC00378430 (abbreviated as 8430), that reduces the SIX1/EYA2 interaction. 8430 partially reversed transcriptional and metabolic profiles mediated by SIX1 overexpression and reversed SIX1-induced TGFβ signaling and EMT. 8430 was well tolerated when delivered to mice and significantly suppressed breast cancer-associated metastasis without significantly altering primary tumor growth. Thus, we have demonstrated for the first time that pharmacologic inhibition of the SIX1/EYA2 complex and associated phenotypes is sufficient to suppress breast cancer metastasis. SIGNIFICANCE: These findings identify and characterize a novel inhibitor of the SIX1/EYA2 complex that reverses EMT phenotypes suppressing breast cancer metastasis.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-0435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510951PMC
June 2020

Two Sides of the Same Coin: The Role of Developmental pathways and pluripotency factors in normal mammary stem cells and breast cancer metastasis.

J Mammary Gland Biol Neoplasia 2020 06 22;25(2):85-102. Epub 2020 Apr 22.

Integrated Physiology Program, University of Colorado Anschutz Medical Campus, RC1-North, P18-6115, 12800 East 19th Ave, Aurora, CO, 80045, USA.

Breast cancer initiation and progression are often observed as the result of dysregulation of normal developmental processes and pathways. Studies focused on normal mammary stem/progenitor cell activity have led to an understanding of how breast cancer cells acquire stemness-associated properties including tumor initiation, survival and multi-lineage differentiation into heterogeneous tumors that become difficult to target therapeutically. Importantly, more recent investigations have provided valuable insight into how key developmental regulators can impact multiple phases of metastasis, where they are repurposed to not only promote metastatic phenotypes such as migration, invasion and EMT at the primary site, but also to regulate the survival, initiation and maintenance of metastatic lesions at secondary organs. Herein, we discuss findings that have led to a better understanding of how embryonic and pluripotency factors contribute not only to normal mammary development, but also to metastatic progression. We further examine the therapeutic potential of targeting these developmental pathways, and discuss how a better understanding of compensatory mechanisms, crosstalk between pathways, and novel experimental models could provide critical insight into how we might exploit embryonic and pluripotency regulators to inhibit tumor progression and metastasis.
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http://dx.doi.org/10.1007/s10911-020-09449-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395869PMC
June 2020

SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1.

Front Oncol 2019 20;9:1450. Epub 2019 Dec 20.

Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.

As a critical member of the Retinal Determination Gene Network (RDGN), SIX1 has been regarded as a tumor promoter in various types of cancer. However, its role in papillary thyroid carcinoma (PTC) has never been investigated. In this study, thyroid carcinoma tissue microarray staining was employed to identify the expression patterns of SIX1 and its co-activator EYA1. Papillary thyroid cancer cell lines, BCPAP, and TPC-1 cells were used to investigate the potential mechanism of SIX1 and . Flow cytometry analysis, MTT assay, the growth curve assay, colony formation assay, EdU incorporation and xenograft assay were performed to demonstrate the role of SIX1 in the malignant change of PTC cells. Western blot and Real-time PCR were used to detect the interaction among the SIX1, EYA1, and STAT3 signaling. In comparison with normal tissue, high expressions of SIX1 and EYA1 were associated with a malignant tumor. Importantly, SIX1 strongly correlated with EYA1 in thyroid carcinoma tissue microarray. Functional assays indicated SIX1 increased EYA1 expression by stabilizing EYA1 at the post-transcriptional level. Besides, SIX1 promoted the proliferation and invasion of thyroid carcinoma via activation of STAT3 signaling and its downstream targets in an EYA1-dependent manner. SIX1 can integrate with EYA1 to contribute to PTC development via activation of the classical STAT3 signaling. These data suggested targeting the abnormal activation of the SIX1/EYA1 complex may represent a novel therapeutic strategy for advanced PTC patients.
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http://dx.doi.org/10.3389/fonc.2019.01450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933607PMC
December 2019

A prognostic eight-gene expression signature for patients with breast cancer receiving adjuvant chemotherapy.

J Cell Biochem 2019 Nov 6. Epub 2019 Nov 6.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Breast cancer is a popularly diagnosed malignant tumor. Genomic profiling studies suggest that breast cancer is a disease with heterogeneity. Chemotherapy is one of the chief means to treat breast cancer, while its responses and clinical outcomes vary largely due to the conventional clinicopathological factors and inherent chemosensitivity of breast cancer. Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, our study established a multi-mRNA-based signature model and constructed a relative nomogram in predicting distant-recurrence-free survival for patients receiving surgery and following chemotherapy. We constructed a signature of eight mRNAs (IPCEF1, SYNDIG1, TIGIT, SPESP1, C2CD4A, CLCA2, RLN2, and CCL19) with the LASSO model, which was employed to separate subjects into groups with high- and low-risk scores. Obvious differences of distant-recurrence-free survival were found between these two groups. This eight-mRNA-based signature was independently associated with the prognosis and had better prognostic value than classical clinicopathologic factors according to multivariate Cox regression results. Receiver operating characteristic results demonstrated excellent performance in diagnosing 3-year distant-recurrence by the eight-mRNA signature. A nomogram that combined both the eight-mRNA-based signature and clinicopathological risk factors was constructed. Comparing with an ideal model, the nomograms worked well both in the training and validation sets. Through the results that the eight-mRNA signature effectively classified patients into low- and high-risk of distant recurrence, we concluded that this eight-mRNA-based signature played a promising predictive role in prognosis and could be clinically applied in breast cancer patients receiving adjuvant chemotherapy.
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http://dx.doi.org/10.1002/jcb.29550DOI Listing
November 2019

A prognostic eight-lncRNA expression signature in predicting recurrence of ER-positive breast cancer receiving endocrine therapy.

J Cell Physiol 2020 05 29;235(5):4746-4755. Epub 2019 Oct 29.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Long noncoding RNAs (lncRNAs) have the main role in the tumorigenesis of breast cancer. In the present study, lncRNA expression profiling was collected to identify a lncRNA expression signature from the Gene Expression Omnibus database. An eight-lncRNA signature was established to predict the survival of patients with estrogen receptor (ER)-positive breast cancer receiving endocrine therapy. Patients were separated into a low-risk group and a high-risk group based on this signature. Patients in high-risk group have worse survival compared to those in low-risk group using Kaplan-Meier curve analysis with log-rank test. Receiver operating characteristic analysis suggested good diagnostic efficiency of the eight-lncRNA signature. When adjusting the clinical features, including age, grade, lymph node status, and tumor size, this signature was independently associated with the relapse-free survival. The prognostic value of the lncRNA prognostic model was then validated in validation sets. When validated in a cohort of patients treated with neoadjuvant chemotherapy and endocrine therapy, this signature demonstrated good performance as well. Besides, we have built a nomogram that integrated the conventional clinicopathological features and the eight-lncRNA-based signature. To sum up, our results indicated that the eight-lncRNA prognostic model was a reliable tool to group patients at high and low risk of disease relapse. This signature may have possible implication in prognostic evaluations of patients with ER-positive breast cancer receiving endocrine therapy.
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http://dx.doi.org/10.1002/jcp.29352DOI Listing
May 2020

A prognostic 10-lncRNA expression signature for predicting the risk of tumour recurrence in breast cancer patients.

J Cell Mol Med 2019 10 20;23(10):6775-6784. Epub 2019 Aug 20.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death among females. Multiple molecular alterations are observed in breast cancer. LncRNA transcripts were proved to play important roles in the biology of tumorigenesis. In this study, we aimed to identify lncRNA expression signature that can predict breast cancer patient survival. We developed a 10-lncRNA signature-based risk score which was used to separate patients into high-risk and low-risk groups. Patients in the low-risk group had significantly better survival than those in the high-risk group. Receiver operating characteristic analysis indicated that this signature exhibited excellent diagnostic efficiency for 1-, 3- and 5-year disease-relapse events. Moreover, multivariate Cox regression analysis demonstrated that this 10-lncRNA signature was an independent risk factor when adjusting for several clinical signatures such as age, tumour size and lymph node status. The prognostic value of risk scores was validated in the validation set. In addition, a nomogram was established and the calibration plots analysis indicated the good performance and clinical utility of the nomogram. In conclusion, our results demonstrated that this 10-lncRNA signature effectively grouped patients at low and high risk of disease recurrence.
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http://dx.doi.org/10.1111/jcmm.14556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787455PMC
October 2019

Weighted gene correlation network analysis identifies RSAD2, HERC5, and CCL8 as prognostic candidates for breast cancer.

J Cell Physiol 2020 01 21;235(1):394-407. Epub 2019 Jun 21.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

As the most commonly diagnosed malignant tumor in female population, the prognosis of breast cancer is affected by complex gene interaction networks. In this research weighted gene co-expression network analysis (WGCNA) would be utilized to build a gene co-expression network to identify potential biomarkers for prediction the prognosis of patients with breast cancer. We downloaded GSE25065 from Gene Expression Omnibus database as the test set. GSE25055 and GSE42568 were utilized to validate findings in the research. Seven modules were established in the GSE25065 by utilizing average link hierarchical clustering. Three hub genes, RSAD2, HERC5, and CCL8 were screened out from the significant module (R  = 0.44), which were considerably interrelated to worse prognosis. Within test dataset GSE25065, RSAD2, and CCL8 were correlated with tumor stage, grade, and lymph node metastases, whereas HERC5 was correlated with lymph node metastases and tumor grade. In the validation dataset GSE25055 and RSAD2 expression was correlated with tumor grade, stage, and size, whereas HERC5 was related to tumor stage and tumor grade, and CCL8 was associated with tumor size and tumor grade. Multivariable survival analysis demonstrated that RSAD2, HERC5, and CCL8 were independent risk factors. In conclusion, the WGCNA analysis conducted in this study screened out novel prognostic biomarkers of breast cancer. Meanwhile, further in vivo and in vitro studies are required to make the clear molecular mechanisms.
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http://dx.doi.org/10.1002/jcp.28980DOI Listing
January 2020

Overexpression of ASPM, CDC20, and TTK Confer a Poorer Prognosis in Breast Cancer Identified by Gene Co-expression Network Analysis.

Front Oncol 2019 24;9:310. Epub 2019 Apr 24.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Breast cancer is one of the most common malignancies among females, and its prognosis is affected by a complex network of gene interactions. In this study, we constructed free-scale gene co-expression networks using weighted gene co-expression network analysis (WGCNA). The gene expression profiles of GSE25055 were downloaded from the Gene Expression Omnibus (GEO) database to identify potential biomarkers associated with breast cancer progression. GSE42568 was downloaded for validation. A total of 9 modules were established via the average linkage hierarchical clustering. We identified 3 hub genes (ASPM, CDC20, and TTK) in the significant module ( = 0.52), which were significantly correlated with poor prognosis both in test and validation datasets. In the datasets GSE25055 and GSE42568, higher expression levels of ASPM, CDC20, and TTK correlated with advanced tumor grades. Immunohistochemistry data from the Human Protein Atlas also demonstrated that their protein levels were higher in tumor samples. According to gene set enrichment analysis, 4 commonly enriched pathways were identified: cell cycle pathway, DNA replication pathway, homologous recombination pathway, and P53 signaling pathway. In addition, strong correlations were found among their expression levels. In conclusion, our WGCNA analysis identified candidate prognostic biomarkers for further basic and clinical researches.
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http://dx.doi.org/10.3389/fonc.2019.00310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492458PMC
April 2019

EYA1 promotes cell migration and tumor metastasis in hepatocellular carcinoma.

Am J Transl Res 2019 15;11(4):2328-2338. Epub 2019 Apr 15.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University 169 Donghu Road, Wuhan 430071, P. R. China.

Hepatocellular carcinoma (HCC) patients are at high risk for both local recurrence and distant metastasis and tightly associated with poor prognosis. Exploring the molecular mechanism will provide a new opportunity in developing personal treatment for advanced HCC patients. As a critical member of the Retinal Determination Gene Network (RDGN), EYA1 has been identified as a tumor promoter in various cancers; however, its role in HCC has never been investigated. The present study was aimed to explore the role of EYA1 in HCC development. By analyzing public microarray datasets, we found that the mRNA level was enhanced in HCC, which was significantly correlated with an aggressive phenotype and poor prognosis. Besides, EYA1 was coordinated with the fibronectin type III domain containing 3B (FNDC3B) to promote the migration and invasion of HCC cells. Western blot assays indicated that EYA1 not only increased the abundance of FNDC3B but also contributed to Epithelial-Mesenchymal Transition (EMT)-like phenotype change, like increased N-cadherin and decreased E-cadherin expression. Collectively, this study suggested that EYA1 activated FNDC3B to promote the migration and invasion in HCC. The aberrant expressions of EYA1 and FNDC3B may become the poor predictors for HCC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511787PMC
April 2019

Sapylin (OK-432) alters inflammation and angiogenesis in vivo and vitro.

Biomed Pharmacother 2019 May 4;113:108706. Epub 2019 Mar 4.

Department of Thyroid and Breast Surgery, Wuhan University Zhongnan Hospital, 169 Donghu Road, Wuhan, 430071, PR China. Electronic address:

Background: The occurrence of seroma formation and long-term wound healing remain challenging complications after modified radical mastectomy. Sapylin is a drug used to reduce seroma formation and enhance wound closure, but these results remain controversial. We aimed to investigate the potential mechanism.

Methods: A prospective, consecutive cohort study included 120 patients diagnosed with breast cancer who underwent modified radical mastectomy was designed. Patients were randomized into two group, using or not using OK-432 (sixty patients per group) during surgeries. Patients' drainage fluids were collected for three days after surgery. Inflammatory cytokines and chemokines were measured with ELISA assays. The proliferative, migratory, and angiogenic capacity of HUVEC and HFL1 cells HUVEC and HFL1 cells were measured after being treated with drainage fluids.

Results: Our clinic data showed that there was no statistical significance between the two groups in patient characteristics before surgery. However, the outcomes of patients in experimental group were significantly better than those in control group. In vitro studies, the results of ELISA assays showed that several cytokines, including IL-1a, IL-6, TGF-β1, bFGF and VEGF were increased in the drainage fluids treated with Sapylin. The proliferative, migratory, and angiogenic capacity of HUVEC and HFL1 cells were significantly enhanced after being treated with Sapylin group drainage fluids.

Conclusion: Sapylin could stimulate the body to secrete a variety of cytokines to promote wound healing by promoting endothelial cell proliferation and migration, angiogenesis and by increasing fibroblast migration and collagen deposition.
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http://dx.doi.org/10.1016/j.biopha.2019.108706DOI Listing
May 2019

Parathyroid autotransplantation at a novel site for better evaluation of the grafted gland function: study protocol for a prospective, randomized controlled trial.

Trials 2019 Jan 31;20(1):96. Epub 2019 Jan 31.

Department of Thyroid and Breast Surgery, Zhongnan Hospital, Wuhan University, 169 Donghu Road, Wuhan, Hubei, 430071, China.

Background: Hypoparathyroidism is one of the most common complications encountered in thyroidectomy. In addition to parathyroid in-situ preservation, parathyroid autotransplantation (PA) is another important remedial method for patients whose parathyroid glands have been removed. However, an accurate evaluation method for the function of a transplanted parathyroid is lacking. Our preliminary study indicated that patients with PA at novel sites near antecubital veins had higher serum concentrations of parathyroid hormone (PTH). Therefore, the main hypothesis is that a grafted site closer to the cephalic vein is more useful for better evaluation of transplanted parathyroid function. This study aims to confirm the more efficient and accurate evaluation system through a prospective, randomized controlled trial.

Methods: In total, 280 patients will be enrolled in this study and randomly divided into two groups: 140 patients with transplanted parathyroid glands in the traditional sites (group A) and the other 140 transplanted in the novel sites (group B), close to the antecubital veins. The serum concentration of PTH and calcium ion from both forearms will be measured and monitored regularly for 12 months. The primary outcome of this trial will be the survival of grafted glands, defined as the ratio of PTH between the grafted vs. the non-grafted forearms being no less than 1.5. The secondary outcome is hypoparathyroidism, defined as the PTH level from the non-grafted forearms being less than 15 pg/ml (normal range 15-65 pg/ml).

Discussion: Our results from this study should provide a more accurate method to evaluate the function of transplanted parathyroid glands by comparing PTH concentrations in both the grafted and non-grafted forearms following PA at novel sites. A better PTH measurement is helpful not only for the management of postoperative patients, but also for further identification of factors affecting PA success.

Trial Registration: ClinicalTrials.gov, ID: NCT02906748 . Registered on 16 March 2016.
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http://dx.doi.org/10.1186/s13063-019-3195-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357396PMC
January 2019

Prognostic Genes of Breast Cancer Identified by Gene Co-expression Network Analysis.

Front Oncol 2018 11;8:374. Epub 2018 Sep 11.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Breast cancer is one of the most common malignancies. The molecular mechanisms of its pathogenesis are still to be investigated. The aim of this study was to identify the potential genes associated with the progression of breast cancer. Weighted gene co-expression network analysis (WGCNA) was used to construct free-scale gene co-expression networks to explore the associations between gene sets and clinical features, and to identify candidate biomarkers. The gene expression profiles of GSE1561 were selected from the Gene Expression Omnibus (GEO) database. RNA-seq data and clinical information of breast cancer from TCGA were used for validation. A total of 18 modules were identified via the average linkage hierarchical clustering. In the significant module ( = 0.48), 42 network hub genes were identified. Based on the Cancer Genome Atlas (TCGA) data, 5 hub genes (CCNB2, FBXO5, KIF4A, MCM10, and TPX2) were correlated with poor prognosis. Receiver operating characteristic (ROC) curve validated that the mRNA levels of these 5 genes exhibited excellent diagnostic efficiency for normal and tumor tissues. In addition, the protein levels of these 5 genes were also significantly higher in tumor tissues compared with normal tissues. Among them, CCNB2, KIF4A, and TPX2 were further upregulated in advanced tumor stage. In conclusion, 5 candidate biomarkers were identified for further basic and clinical research on breast cancer with co-expression network analysis.
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http://dx.doi.org/10.3389/fonc.2018.00374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141856PMC
September 2018

The analysis of GM (1, 1) grey model to predict the incidence trend of typhoid and paratyphoid fevers in Wuhan City, China.

Medicine (Baltimore) 2018 Aug;97(34):e11787

Wuhan Centers for Disease Prevention and Control Center for Translational Medicine, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, China.

Typhoid and paratyphoid fevers (TPF), systemic emerging infectious diseases, is a serious health problem for society. If the incidence trend of TPF can be predicted, prevention and control measures can be taken in advance to reduce the harm to the people's health.Grey Model First Order One Variable [GM (1, 1)] was applied to predict the incidence trend of TPF with the incidence data of TPF in Wuhan City of China from 2004 to 2015. The original data were acquired from the national surveillance system.The GM (1, 1) model was established as ŷ (t + 1) = 0.88 e + 0.15. The goodness-of-fit test indicated that the precision (degree 2) was qualified (C = 0.40, P = .91). We further compared actual values with predicted values in 2016 and found that GM (1, 1) model we built has excellent performance in incidence trend prediction.Our prediction shows that the TPF incidences in Wuhan City will be slowly decreasing in the next 3 years. It is, however, still necessary to strengthen the comprehensive prevention and control to reduce the incidence level of TPF.
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http://dx.doi.org/10.1097/MD.0000000000011787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6112867PMC
August 2018

Impact of Gender and Age on the Prognosis of Differentiated Thyroid Carcinoma: a Retrospective Analysis Based on SEER.

Horm Cancer 2018 10 16;9(5):361-370. Epub 2018 Jul 16.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

The incidence of thyroid cancer in females is significantly higher than that in males; however, females are more likely to have more favorable outcomes. We aimed to determine the characteristics of differentiated thyroid carcinoma (DTC) subtypes in males and females, and to compare their clinical behavior and survival. A total of 68,337 cases were recruited from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. The disease-specific survival (DSS) of follicular variant papillary thyroid carcinoma (FVPTC) and follicular thyroid carcinoma (FTC) were similar to that of classical variant papillary thyroid carcinoma (CPTC) in male patients (FVPTC vs. CPTC, adjusted hazard ratio (aHR) = 0.947, P = 0.776; FTC vs. CPTC, aHR = 1.512, P = 0.104). In premenopausal female (< 55 years old), FVPTC had better DSS than CPTC (aHR = 0.321, P = 0.038) while FTC had worse DSS than CPTC (aHR = 3.272, P = 0.013); in postmenopausal female, FTC had poorer prognosis than CPTC (aHR = 2.145, P = 0.002), no statistical difference was found between CPTC and FVPTC (aHR = 0.724, P = 0.087). For patients younger than 55 years, women had significantly better DSS compared with men with CPTC (aHR = 0.376, P < 0.001) and FVPTC (aHR = 0.102, P < 0.001). However, no difference was observed in patients older than 55 years. Interestingly, outcomes of FTC were not affected by gender in patients of all ages. These results suggested that different clinical behaviors and outcomes of DTC subtypes should be considered in patients with different genders.
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http://dx.doi.org/10.1007/s12672-018-0340-yDOI Listing
October 2018

The role of radioactive iodine therapy in papillary thyroid cancer: an observational study based on SEER.

Onco Targets Ther 2018 19;11:3551-3560. Epub 2018 Jun 19.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Background: Papillary thyroid cancer (PTC) is a common endocrine malignancy with relatively good prognosis. Radioactive iodine (RAI) is considered effective for patients with total or nearly total thyroidectomy, but the beneficial effects of RAI are still controversial.

Materials And Methods: To determine whether RAI therapy could improve the survival rates of PTC patients, we conducted a retrospective analysis using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Disease-specific survival (DSS) was obtained using multivariate Cox proportional hazard regressions.

Results: DSS was improved by RAI ablation in patients with tumor >2 cm, age >45 years and gross extrathyroidal or lymph node metastasis. In a further analysis, RAI therapy did not improve the DSS in patients with tumor <2 cm except those with distant metastasis. For patients with tumor >2 cm, those involving gross extrathyroidal extension, age >45 years or disease in the lymph nodes, DSS was improved after RAI therapy. Patients with distant metastasis always benefited from RAI ablation.

Conclusion: RAI ablation should be recommended to patients with tumor <2 cm and distant metastasis or patients with tumor >2 cm and one of the following risk factors: gross extrathyroidal extension, age >45 years, lymph node and distant metastases.
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http://dx.doi.org/10.2147/OTT.S160752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016280PMC
June 2018

Bioinformatic analysis and identification of potential prognostic microRNAs and mRNAs in thyroid cancer.

PeerJ 2018 4;6:e4674. Epub 2018 May 4.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Thyroid cancer is one of the most common endocrine malignancies. Multiple evidences revealed that a large number of microRNAs and mRNAs were abnormally expressed in thyroid cancer tissues. These microRNAs and mRNAs play important roles in tumorigenesis. In the present study, we identified 72 microRNAs and 1,766 mRNAs differentially expressed between thyroid cancer tissues and normal thyroid tissues and evaluated their prognostic values using Kaplan-Meier survival curves by log-rank test. Seven microRNAs (miR-146b, miR-184, miR-767, miR-6730, miR-6860, miR-196a-2 and miR-509-3) were associated with the overall survival. Among them, three microRNAs were linked with six differentially expressed mRNAs (miR-767 was predicted to target COL10A1, PLAG1 and PPP1R1C; miR-146b was predicted to target MMP16; miR-196a-2 was predicted to target SYT9). To identify the key genes in the protein-protein interaction network , we screened out the top 10 hub genes (NPY, NMU, KNG1, LPAR5, CCR3, SST, PPY, GABBR2, ADCY8 and SAA1) with higher degrees. Only LPAR5 was associated with the overall survival. Multivariate analysis demonstrated that miR-184, miR-146b, miR-509-3 and LPAR5 were an independent risk factors for prognosis. Our results of the present study identified a series of prognostic microRNAs and mRNAs that have the potential to be the targets for treatment of thyroid cancer.
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http://dx.doi.org/10.7717/peerj.4674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937477PMC
May 2018

Racial disparities of differentiated thyroid carcinoma: clinical behavior, treatments, and long-term outcomes.

World J Surg Oncol 2018 Mar 5;16(1):45. Epub 2018 Mar 5.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei, 430071, China.

Background: The incidence of thyroid cancer in black Americans is significantly lower than that in white Americans, and the impact of race on the prognosis of thyroid cancer remains controversial. The purpose of this study was to determine the risk factors for survival in black and white patients and to compare the survival of differentiated thyroid carcinoma subtypes between these two races. We further investigated the association of lymph node and distant metastases with races.

Methods: This is a retrospective analysis using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A total of 70,346 cases were included in our study. Patients' demographics and cancer- and treatment-related characteristics were compared between the black and white Americans using chi-square and Fisher's exact tests. For multivariate analysis, Cox proportional hazards regression were used to assess the association between potential risk factors and the survival in black and white patients.

Result: Black Americans had a worse overall survival than white Americans (HR = 1.127, P = 0.002). While disease-specific survival (DSS) was comparable, the risk factors for DSS were different between white and black Americans. Black Americans had less lymph node metastasis of classical variant papillary thyroid carcinoma (CPTC, OR = 0.476, P < 0.001) and follicular variant papillary thyroid carcinoma (FVPTC, OR = 0.522, P < 0.001), but not follicular thyroid carcinoma (FTC). However, black Americans with FVPTC, but not CPTC or FTC, had a higher potential of distant metastasis (OR = 1.715, P = 0.026). Furthermore, only white patients with tumor > 2 cm and lymph node metastasis benefited from radioactive iodine.

Conclusions: The risk factors for DSS were significantly different in white and black patients. The impact of race should be considered in treatment strategy for thyroid cancer.
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http://dx.doi.org/10.1186/s12957-018-1340-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836433PMC
March 2018

Dachshund 1 is Differentially Expressed Between Male and Female Breast Cancer: A Matched Case-Control Study of Clinical Characteristics and Prognosis.

Clin Breast Cancer 2018 10 2;18(5):e875-e882. Epub 2018 Feb 2.

Department of Thyroid and Breast Surgery, Zhongnan Hospital, Wuhan University, Wuhan, P.R. China. Electronic address:

Introduction: Male breast cancer (MBC) is rare and little is known about its biological behavior. In this study we described clinical characteristics and prognosis of MBC and evaluated roles of different factors between MBC and female breast cancer (FBC).

Patients And Methods: We retrospectively reviewed 42 MBC patients matched with 84 consecutive FBC patients with similar year, age, tumor, node, metastases (TNM) stage, and estrogen receptor (ER) expression from 2003 to 2016. Their clinical characteristics, treatments, and prognosis were analyzed, and immunohistochemistry for androgen receptor (AR), dachshund 1 (DACH1), sine oculis 1 (SIX1), eyes absent 1, B-cell lymphoma-2, and p53 were performed on paraffin sections.

Results: MBC constituted 0.56% (42 of 7561) of consecutive breast cancer and had a median age of 55 years. The 14 paraffin samples from men and 28 from women expressed all the assessed proteins, and DACH1 was significantly higher in women (P = .043). Body mass index (P = .023) and DACH1 (P = .034) were correlated with MBC prognosis, whereas the expression of AR (P = .049), SIX1 (P = .048), surgery (P < .001), and chemotherapy (P = .001) were important for FBC in addition to already known factors: tumor size and location, TNM stage (lymph nodes and organ metastasis), radiotherapy, and ER and human epidermalgrowth factor receptor-2 (HER2) expression. No distinct difference in recurrence was observed between MBC and FBC (P = .667).

Conclusion: In this study we found that DACH1 was expressed less in MBC and HER2 was expressed more in FBC. They were respectively correlated with MBC and FBC prognosis. Although no significant differences were observed between MBC and FBC prognosis, DACH1, SIX1, and AR expression requires greater attention to develop treatment strategies for MBC and FBC.
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http://dx.doi.org/10.1016/j.clbc.2018.01.011DOI Listing
October 2018

Surgical management for follicular variant of papillary thyroid carcinoma.

Oncotarget 2017 Oct 16;8(45):79507-79516. Epub 2017 Jun 16.

Department of Breast and Thyroid Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, P.R. China.

Background And Aims: For most patients with follicular variant of papillary thyroid carcinoma (FVPTC), surgery is required, while the surgical management remains controversial. We aim to further understanding of treatment of FVPTC and to determine whether specific features could be identified for the decision of surgical strategy.

Materials And Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program database during 2003 and 2013. 26700 patients were eligible and stratified by tumor size or extension. Survival rates were compared using multivariate Cox proportional hazard regressions.

Results: Of the total death of 1041, 136 patients died from thyroid cancer. Most patients (79.1%) underwent total thyroidectomy while only a little part of patients (8.2%) underwent lobectomy. Patients receiving radioisotopes had significantly better overall survival (OS) (HR = 0.659, < 0.001), but showed no differences on disease-specific survival (DSS). No statistical difference was found between total thyroidectomy and lobectomy in multivariate analysis when controlling for tumor size. While for tumor > 2 cm with extrathyroidal extension, lobectomy had significantly worse OS (aHR = 3.364, = 0.010) and DSS (aHR = 5.494, = 0.032) compared to total thyroidectomy. Multivariate analysis demonstrated that advanced age, male, higher grade, extrathyroidal extension, lymph nodes metastases and distant metastases had negative effects on OS and DSS controlling for the remaining variables (each < 0.05).

Conclusions: The results of our study revealed total thyroidectomy could benefit the survival for patients whose tumors > 2 cm with extrathyroidal extension, total thyroidectomy should be recommended for those patients. Lots of factors should be taken into consideration on the decision of surgical treatment.
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http://dx.doi.org/10.18632/oncotarget.18525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668063PMC
October 2017

Sapylin promotes wound healing in mouse skin flaps.

Am J Transl Res 2017 15;9(6):3017-3026. Epub 2017 Jun 15.

Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University169 Dong Hu Road, Wuhan 430071, P. R. China.

Seroma formation is one of the most common complications after modified radical mastectomy. Sapylin is an agent used to reduce seroma formation following breast cancer surgery. In this article, we aimed to identify the potential mechanism by which Sapylin reduced seroma formation. Thirty-six female C57 mice were randomly divided into three groups. All mice were anaesthetized and a skin flap was generated on their abdomens. Each group was treated with normal saline, 0.5 KE/ml of Sapylin, or 50% hypertonic glucose, respectively. On day 3 and day 7 after the surgery, six mice in each group were sacrificed. Skin flap samples were collected and markers of angiogenesis, collagen synthesis, fibroplasia and matrix remodeling were detected. The skin flaps from the Sapylin- or hypertonic glucose-treated mice closed faster than the skin flaps from the mice treated with normal saline. The neovessel density was higher in the skin flaps from the mice in the Sapylin group than those in the other two groups. Increased mRNA and protein expression of angiogenesis markers (VEGF-A and HIF-1α) and collagen synthesis markers (FGF2 and TGF-β1) were observed in the mice in the Sapylin group compared with the saline- or hypertonic glucose-treated mice. The extracellular matrix remodeling marker MMP2 was induced by Sapylin only in the early phase (day 3). In conclusion, Sapylin accelerated wound closure, and promoted angiogenesis, collagen synthesis and the remodeling process, which improved wound healing. Considering the close relationship between wound healing and seroma formation, Sapylin may reduce seroma formation after modified radical mastectomy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489901PMC
June 2017

The Identification, Preservation and Classification of the External Branch of the Superior Laryngeal Nerve in Thyroidectomy.

World J Surg 2017 10;41(10):2521-2529

Department of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China.

Background: Avoiding injury to the external branch of the superior laryngeal nerve is one of the major challenges during thyroid operation. The aim of this study was to propose a practical classification of the external branch of the superior laryngeal nerve.

Methods: A retrospective study of total thyroidectomy was performed. Totally 240 patients were included, with 480 external branches of the superior laryngeal nerves explored by intraoperative neuromonitoring. The classification of the external branch of the superior laryngeal nerve was determined by the distance between the upper edge of the superior thyroid pole and the lowest point of the nerve when the thyroid lobe was retracted in the lateral and inferior direction. Multinomial logistic regression analysis was run to predict the type of the nerve from several variables.

Results: The identification rate of the external branch of the superior laryngeal nerve was 98.54% (473 of 480 nerves). Higher ratio of longitudinal size of the thyroid lobe to ipsilateral neck length increased the likelihood of that both the type 2 and 3 nerve with respect to type 1 nerve, with OR 2.72, 95% CI = 1.21-6.12 and OR 5.30, 95% CI = 2.09-13.44, respectively. (1a) The nerve whose lowest point (entry into the muscle) was located more than 1 cm above the horizontal plane passing the upper border of superior thyroid pole. (1b) The nerve whose lowest point (the point right above the superior thyroid pole) was located more than 1 cm above the plane. (2a) The nerve whose lowest point (entry into the muscle) was located within 1 cm above the plane. (2b) The nerve whose lowest point (the point right above the superior thyroid pole) was located within 1 cm above the plane. (3a) The nerve whose lowest point (entry into the muscle) was located below the plane. (3b) The nerve whose lowest point (the point right below the superior thyroid pole) was located anterior to the gland. (3c) The nerve whose lowest point (the point right below the superior thyroid pole) was located posterior to the gland.

Conclusions: Identification rate of the external branch of the superior laryngeal nerve by intraoperative neuromonitoring was significantly high. Understanding the new practical classification of the nerve allows for better identification and function preservation of this nerve during thyroidectomy.
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http://dx.doi.org/10.1007/s00268-017-4046-zDOI Listing
October 2017

A prospective cohort study of novel functional types of parathyroid glands in thyroidectomy: In situ preservation or auto-transplantation?

Medicine (Baltimore) 2016 Dec;95(52):e5810

Department of Thyroid and Breast Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, P.R. China.

The best method of preventing hypoparathyroidism after thyroidectomy is to keep parathyroid glands in situ. However, hypoparathyroidism still regularly occurs with the existing parathyroid classification system, and the incidence of permanent hypoparathyroidism has not been reduced. We created a novel system for classifying parathyroid glands that can guide parathyroid preservation in thyroidectomy.We prospectively observed parathyroid glands using the new system in 218 neck surgeries, compared with 132 under the traditional system from January 2014 to September 2015 at a single clinic center. Briefly, we classified parathyroid glands as follows: Type A, no dependency on the thyroid; B1, partial blood supply from the thyroid but retains adequate blood supply after removal of the thyroid; B2, partial blood supply from the thyroid and becomes devascularized after the removal of the thyroid; B3, blood supply mostly from the thyroid; and C, blood supply completely dependent on the thyroid. The classifications were used to decide between in situ preservation or auto-transplantation.The most common type of parathyroid gland was type B1 (53.77%), followed by type A (20.89%), which are the perfect categories for in situ preservation. Type B2 (17.52%) and type B3 (1.21%) have a chance to be kept in situ. For type C (6.61%), in situ preservation is impossible. When in-situ preservation is ruled out, parathyroid auto-transplantation is an alternative, with partial or total gland tissue, depending on the classification and the surgeon's discretion. Among the patients who were classified under the new system, 43.6% presented with transient hypoparathyroidism (symptoms lasting ≤6 months) after surgery, versus 42.4% in the old system, which was not a significant difference. However, permanent hypothyroidism (symptoms lasting >6 months) was not detected in the applied group, but in 3.0% of patients in the nonapplied group (P = 0.01).Our novel functional nomenclature system for parathyroid glands can provide a guide for preserving parathyroid function. For certain types, such as type B2 and C, instead of being kept in situ, auto-transplantation of partial or total parathyroid tissue is a prudent choice to ensure continued function.
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http://dx.doi.org/10.1097/MD.0000000000005810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207601PMC
December 2016

OK-432 (Sapylin) Reduces Seroma Formation After Axillary Lymphadenectomy in Breast Cancer.

J Invest Surg 2017 Feb 18;30(1):1-5. Epub 2016 Jul 18.

a Department of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College , Huazhong University of Science and Technology , Wuhan , P. R. China.

Purpose/aim: Modified radical mastectomy is the standard surgery for breast cancer in developing countries. However, seroma formation regarded as the most frequent postoperative complication limits the therapeutic benefit of mastectomy and axillary surgery. The purpose of this study was to evaluate the efficacy of OK-432 in reducing seroma formation after axillary dissection.

Methods: This prospective cohort study included 80 patients with advanced breast cancer who underwent modified radical mastectomy. Patients were randomized into two groups, which differed with the OK-432 administration. N = 40 patients per group were treated with either OK-432 plus closed suction drainage or drainage-only.

Result: In comparison with the drainage-only group, we found that patients in the OK-432 group had a lower drainage volume (p = .030) and a shorter duration of axillary drainage (p < .01). Besides, the use of OK-432 could reduce the incidence of seroma formation (p < .01) and the volume of seroma (p = .040). There were also significant differences in reducing the chance of evacuative punctures (p = .036) and the healing time (p < .01) between control and OK-432 group.

Conclusion: OK-432 not only shortened the suction drainage duration, but also significantly reduced seroma formation as well as the needs for aspiration punctures after modified radical mastectomy.
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http://dx.doi.org/10.1080/08941939.2016.1204386DOI Listing
February 2017

Left lower limb may be a forbidden region for indwelling needle during operation.

Thromb Res 2016 Aug 20;144:165-8. Epub 2016 Jun 20.

Department of Thyroid and Breast Surgery, Tongji Hospital, HuazhongUniversity of Science and Technology, 1095 Jiefang Avenue, Wuhan, PR China. Electronic address:

Introduction: Information about the incidence and risk factors of venous thromboembolism (VTE) after thyroid operation is limited. This study aimed to analyze the incidence and risk factors of postoperative VTE in patients who had undergone thyroid surgery.

Materials And Methods: A prospective, multi-center cohort study was performed from June 2013 to June 2015 in 3 hospitals throughout South Central China. We analyzed 5029 patients who had undergone thyroid operation and received no VTE prophylaxis postoperatively. For the diagnosis of deep vein thrombosis (DVT), bilateral whole-leg ultrasound was conducted in patients with a high pretest probability of DVT. Lung ventilation/perfusion scintigraphy, pulmonary angiography, or helical computed tomography was implemented in patients suspected to have pulmonary embolism (PE).

Results: DVT was diagnosed in 18 patients (0.36%). No patient was diagnosed with PE. Binomial logistic regression analysis revealed that age and left lower limb intraoperative venous access (IVA) were significant risk factors for DVT. The incidence of DVT increased as the number of risk factors increased.

Conclusions: VTE is uncommon in patients who have undergone thyroid surgery. The left lower limb was not an appropriate insertion site IVA. Pharmacologic thromboprophylaxis was not mandatory, particularly in those patients without risk factors.
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http://dx.doi.org/10.1016/j.thromres.2016.06.021DOI Listing
August 2016

The retinal determination gene network: from developmental regulator to cancer therapeutic target.

Oncotarget 2016 Aug;7(31):50755-50765

Department of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College, Huazhang University of Science and Technology, Wuhan, P.R. China.

Although originally identified for its function in Drosophila melanogaster eye specification, the Retinal Determination Gene Network (RDGN) is essential for the development of multiple organs in mammals. The RDGN regulates proliferation, differentiation and autocrine signaling, and interacts with other key signaling pathways. Aberrant expression of RDGN members such as DACH, EYA and SIX contributes to tumor initiation and progression; indeed, the levels of RDGN members are clinically prognostic factors in various cancer types. Stimulation or suppression of the activities of these crucial components can block cancer cell proliferation, prevent cancer stem cell expansion and even reverse the EMT process, thereby attenuating malignant phenotypes. Thus, cancer therapeutic interventions targeting RDGN members should be pursued in future studies.
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http://dx.doi.org/10.18632/oncotarget.9394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5226618PMC
August 2016

Interplay of retinal determination gene network with TGF-β signaling pathway in epithelial-mesenchymal transition.

Stem Cell Investig 2015 9;2:12. Epub 2015 Jun 9.

1 Department of Geriatrics, 2 Department of Thyroid and Breast Surgery, 3 Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.

As a fundamental event in the generation of tissues and organs during embryogenesis, the epithelial-mesenchymal transition (EMT) has also been implicated in cancer progression by its ability to alter the plasticity of epithelial cells to acquire invasive properties. Evidence is mounting that ectopic activation of transforming growth factors β (TGF-β)/bone morphogenetic protein (BMP) superfamily members to enhance tumorigenesis and metastasis. In this respect, the Retinal Determination Gene Network (RDGN), which was identified to govern the normal initiation of the morphogenetic furrow in Drosophila, has now been found to be de-regulated in various types of cancers, and the key members of this network, DACH, SIX, and EYA, have emerged as novel co-regulators of TGF- signaling during EMT. Understanding the molecular mechanism by which RDGN regulates TGF-β/BMP signaling to influence EMT may lead to novel strategies for targeted therapies.
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http://dx.doi.org/10.3978/j.issn.2306-9759.2015.05.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923650PMC
June 2016

The gap in injury mortality rates between urban and rural residents of Hubei Province, China.

BMC Public Health 2012 Mar 12;12:180. Epub 2012 Mar 12.

The State Key Laboratory of Virology(2004DA105204) and Department of Epidemiology and Health Statistics, School of Public Health, Wuhan University, 185# Donghu Rd., Wuhan 430071, China.

Background: Injury is a growing public health concern in China. Injury death rates are often higher in rural areas than in urban areas in general. The objective of this study is to compare the injury mortality rates in urban and rural residents in Hubei Province in central China by age, sex and mechanism of injury.

Methods: Using data from the Disease Surveillance Points (DSP) system maintained by the Hubei Province Centers for Disease Control and Prevention (CDC) from 2006 to 2008, injury deaths were classified according to the International Classification of Disease-10th Revision (ICD-10). Crude and age-adjusted annual mortality rates were calculated for rural and urban residents of Hubei Province.

Results: The crude and age-adjusted injury death rates were significantly higher for rural residents than for urban residents (crude rate ratio 1.9, 95% confidence interval 1.8-2.0; adjusted rate ratio 2.4, 95% confidence interval 2.3-2.4). The age-adjusted injury death rate for males was 81.6/100,000 in rural areas compared with 37.0/100,000 in urban areas; for females, the respective rates were 57.9/100,000 and 22.4/100,000. Death rates for suicide (32.4 per 100,000 vs 3.9 per 100,000), traffic-related injuries (15.8 per 100,000 vs 9.5 per 100,000), drowning (6.9 per 100,000 vs 2.3 per 100,000) and crushing injuries (2.0 per 100,000 vs 0.7 per 100,000) were significantly higher in rural areas. Overall injury death rates were much higher in persons over 65 years, with significantly higher rates in rural residents compared with urban residents for suicide (279.8 per 100,000 vs 10.7 per 100,000), traffic-related injuries, and drownings in this age group. Death rates for falls, poisoning, and suffocation were similar in the two geographic groups.

Conclusions: Rates of suicide, traffic-related injury deaths and drownings are demonstrably higher in rural compared with urban locations and should be targeted for injury prevention activity. There is a need for injury prevention policies targeted at elderly residents, especially with regard to suicide prevention in rural areas in Central China.
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http://dx.doi.org/10.1186/1471-2458-12-180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338362PMC
March 2012