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Yang Z.,Shanghai University | Lin F.,Taizhou First Peoples Hospital | Qin B.,Shanghai University | Yan L.,Shanghai University | Renqian Z.,Shanghai University
Journal of Rheumatology | Year: 2015

Objective. To investigate the association between polymyositis (PM)/dermatomyositis (DM) and risks of malignancy. Methods. We searched Pubmed for articles dated before August 16, 2013. Studies were included if they met the following criteria: (1) a cohort or observational study; (2) PM or DM as one of the exposures of interest; (3) cancer as an outcome of interest; and (4) the rate ratio (RR) or standardized incidence ratio (SIR) were available with their 95% CI. We used random-effects or fixed-effects models to calculate the pooled RR according to the heterogeneity test. Results. Twenty publications were included. Compared with the general population, the pooled RR for patients with PM, DM, and PM/DM were 1.62 (95% CI 1.19-2.04), 5.50 (4.31-6.70), and 4.07 (3.02-5.12), respectively. The increased risks were more significant in patients within the first year of myositis diagnosis, male patients, and population-based studies (for DM). A significant association was also found between PM or DM and most site-specific malignancies. However, both PM and DM were not associated with stomach and prostate cancers. Significant heterogeneity was found between studies on association between PM/DM and overall malignancy, but not between PM/DM and the majority of site-specific malignancies, suggesting that that inherent malignancy difference may be a major source of heterogeneity. Conclusion. The present metaanalysis indicates that PM and DM are significantly associated with increased risks of overall malignancy and most site-specific malignancies. The number of studies on association between PM or DM and some malignancies is too small to draw a firm conclusion. Accordingly, more research is needed for these malignancies. Copyright © 2015. All rights reserved.


PubMed | Taizhou First Peoples Hospital and Shanghai University
Type: Journal Article | Journal: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica | Year: 2016

It is necessary and useful to explore prevalence of various systemic autoimmune rheumatic diseases (SARDs) in patients with suspicion of having SARDs and to characterize antinuclear antibodies (ANA) profile for identifying different populations (SARDs and non-SARDs). A total of 5024 consecutive patients with available medical records were investigated, whose sera had been tested for ANA profile, including ANA, anti-dsDNA and anti-extractable nuclear antigen (ENA) antibodies, between 31 January 2012 and 26 March 2014. Only 594 (11.8%) patients were diagnosed with SARDs of those suspected with SARDs. The prevalence of systemic lupus erythematosus (SLE) was highest (3.2%), followed by rheumatoid arthritis (RA) (2.5%), primary Sjgrens syndrome (pSS) (1.7%), ankylosing spondylitis (AS) (1.5%), etc. Of females, SLE also showed the highest prevalence (6%), while of males, AS showed the highest prevalence (1.9%). The prevalence of most SARDs was closely associated with age, except mixed connective tissue disease (MCTD), and the variation characteristics among different age groups were different among various SARDs. The prevalence of ANA was significantly increased in most SARD patients [especially in SLE, systemic sclerosis (SSc) and MCTD]. For anti-ENA antibodies, in contrast to some autoantibodies associated with multiple SARDs (e.g. anti-SSA, SSB, nRNP), others were relatively specific for certain diseases, such as anti-dsDNA, Sm, histone, nucleosome and Rib-P for SLE, anti-SCL-70 for SSc and anti-Jo-1 for polymyositis/dermatomyositis (PM/DM). Of note, ANA profile appeared to be of little significance for AS, ANCA-associated vasculitis (AAV), polymyalgia rheumatic (PMR), adult-onset Stills disease (ASD) and Behcets disease (BD). The younger were more likely to have the presence of anti-dsDNA, Sm, histone or Rib-P for SLE, and anti-SSA for RA or MCTD. No significant differences for frequencies of ANA and anti-ENA autoantibodies were found between sexes in most SARDs, with the exception of RA and AS. The present study suggests that, of patients with SARDs-like clinical manifestations, the proportion of those with true SARDS is small, for most of whom tests for autoantibodies are necessary and useful to help make a prompt and precise diagnosis.


Wang Y.,Capital Medical University | Zhao X.,Capital Medical University | Liu L.,Capital Medical University | Wang D.,Illinois College | And 12 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone. METHODS: In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect. RESULTS: Stroke occurred in 8.2% of patients in the clopidogrel-aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (P = 0.73); the rate of hemorrhagic stroke was 0.3% in each group. CONCLUSIONS: Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. Copyright © 2013 Massachusetts Medical Society.


Hu C.,Wenzhou University | Lin F.,Taizhou First Peoples Hospital | Zhu G.,Wenzhou University | Xue X.,Wenzhou University | And 4 more authors.
International Journal of Oncology | Year: 2013

CXCL14, a new member of the CXC subfamily of chemokines, is differentially expressed in several types of tumors. The expression of CXCL14 and its clinical significance in gastric cancer are unclear to date. In this study, the expression of CXCL14 was detected by quantitative PCR and immunohistochemistry assay. DNA methylation was analyzed by bisulfite sequencing PCR. Student's t-test and Kruskal-Wallis H test were used to evaluate the differences of the CXCL14 expression between the groups. Kaplan-Meier survival curve and Cox regression model were used to evaluate the clinical significance of CXCL14 expression in gastric cancer. Data indicated that the levels of CXCL14 mRNA declined (P<0.001) in gastric carcinoma tissues compared to the paired normal tissues. Immunohistochemical analysis also showed the decrease of CXCL14 protein in the tumor tissue (P<0.001). Analysis of CpG islands methylation in CXCL14 promoter region and first exon area indicated that the abnormal hypermethylation of promoter region in tumor tissue is one of the mechanisms causing the reduction. When gastric cancer cells were demethylated with 5-Aza-2'-deoxycytidine, CXCL14 expression was restored. Downregulation of CXCL14 was associated with the depth of penetration (P<0.001) and positively correlated with prognosis in stage III/IV (P=0.046). In conclusion, it is possible that CXCL14 is involved in the development and progression of gastric cancer. Hypermethylation in the promoter is one of the reasons that CXCL14 has lower expression in gastric adenocarcinoma tissues. The level of CXCL14 expression may be a valuable adjuvant parameter in predicting the prognosis of gastric cancer patients and, thus, a potential therapeutic target.


Li X.-J.,Wenzhou Medical College | Li X.-J.,Taizhou First Peoples Hospital | Zhang X.,Wenzhou Medical College | Lin A.,Wenzhou Medical College | And 2 more authors.
Human Immunology | Year: 2012

The immunotolerant human leukocyte antigen (HLA)-G has direct inhibitory effects on natural killer cells, dendritic cells, T cells and can indirectly induce tolerant regulatory cells. The significance of the aberrant HLA-G expression in malignant contexts has been intensively investigated. In the current study, HLA-G expression in 22 normal cervical tissues, 14 cervical intraepithelial neoplasia (CIN) patients and 129 patients with squamous cell cervical cancer were examined using immunohistochemistry. The association of HLA-G expression with disease progression was calculated with the Pearson Chi-square test. It was found that HLA-G expression was absent in normal cervical tissues, and that HLA-G expression was increased from patients with CIN III (35.7%, 4/14) to patients with cervical cancer (62.8%, 81/129). Among the cervical cancer patients, HLA-G expression in FIGO stage I, II, and stage III+IV was 53.6% (45/84), 76.3% (29/38), and 100.0% (7/7), respectively. Taken together, our findings indicated that HLA-G expression was associated with the disease progression in patients with cervical cancer. © 2012 American Society for Histocompatibility and Immunogenetics.


Chen Z.-Y.,Fudan University | Wang H.,Taizhou First Peoples Hospital | Xu W.,Taizhou First Peoples Hospital | Xu H.,Taizhou First Peoples Hospital | Fu X.,Taizhou First Peoples Hospital
Journal of International Medical Research | Year: 2014

Objective: To measure the plasma concentrations of three endogenous opioid peptides and the levels of preproenkephalin (PPE) and preprodynorphin (PPD) mRNA in peripheral blood lymphocytes of patients during scheduled surgery performed under intravenous general anaesthesia combined with an epidural block. Methods: Patients were anaesthetized and arterial blood was collected at 0 (baseline), 20, 40, 60, and 80 min during surgery. The plasma concentrations of β-endorphin, leucine-enkephalin and dynorphin A were measured using radioimmunoassay. Reverse transcription-polymerase chain reaction was used to measure the levels of PPD and PPE mRNA in peripheral blood lymphocytes collected during surgery. Results: Fifteen patients participated in this prospective study. The plasma concentrations of β-endorphin were significantly lower at all time-points compared with the baseline value. The plasma concentrations of leucine-enkephalin and dynorphin A were significantly lower at 40, 60, and 80 min compared with baseline. The PPD/β-actin ratio was significantly lower at 80 min compared with baseline, while the PPE/β-actin ratio showed no significant change. Conclusion: The level of mRNA from two pre-endogenous opioid peptide genes either decreased or remained unchanged during surgery under intravenous general anaesthesia with epidural block, suggesting that patients remained pain free during surgery. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.


PubMed | Fudan University and Taizhou First Peoples Hospital
Type: Journal Article | Journal: The international journal of biochemistry & cell biology | Year: 2016

Prolyl hydroxylase 2 is a key regulator of hypoxia-inducible factor 1 alpha protein, and has previously been implicated as a tumor suppressor in various cancers. However, the function of prolyl hydroxylase 2 in liver cancer has yet to be elucidated. Characterization of prolyl hydroxylase 2 function and related mechanisms in liver cancer may enable the development of targeted therapy. Here we found that prolyl hydroxylase 2 overexpression in human hepatocellular carcinoma cancer cell lines inhibited cell proliferation, while prolyl hydroxylase 2 knockdown enhanced cell proliferation. Further analyses revealed that the prolyl hydroxylase 2-mediated inhibition of cell proliferation was due to a cell cycle arrest at the G1/S transition. Moreover, the block in cell cycle was facilitated by negative regulation of cyclin D1, a process dependent on the hydroxylase activity of prolyl hydroxylase 2. Using an in vivo xenograft mouse model, we found that the overexpression of prolyl hydroxylase 2 led to a reduction in tumor size. Evaluation of paired human liver cancer patient samples revealed that prolyl hydroxylase 2 protein levels were significantly reduced in 6 of the 10 cancer tissues as compared to their respective normal tissue controls. Furthermore, elevated expression of prolyl hydroxylase 2 was associated with significantly prolonged survival in patients with liver cancer. These results suggest that prolyl hydroxylase 2 plays an important tumor suppressive role in liver cancer and may prove to be of prognostic and therapeutic value.


Lin F.,Taizhou First Peoples Hospital | Ding R.,Taizhou First Peoples Hospital | Zheng S.,Taizhou First Peoples Hospital | Xing D.,Taizhou First Peoples Hospital | And 3 more authors.
Cancer Cell International | Year: 2014

Background: MicroRNAs (miRNAs) are a large group of post-transcriptional gene regulators that potentially play a critical role in tumorigenesis. Increasing evidences indicate that miR-744 deregulated in numerous human cancers including hepatocellular carcinoma (HCC). However, its role in HCC carcinogenesis remains poorly defined. In this study, we investigated the roles of miR-744 in tumor growth of HCC.Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was conducted to detect the expression of miR-744 and Immunohistochemistry was performed to detect expression of c-Myc in HCC specimens and adjacent normal tissues. The biological functions of miR-744 were determined by cell proliferation and cell cycle assay. Furthermore, cell lines transfected with miR-744 mimics were analyzed in vitro. Luciferase reporter assays was performed to confirm whether miR-744 regulated the expression of c-Myc.Results: Our results showed that the expression of miR-744 was frequently down-regulated in both HCC tissues and cells. Furthermore, restoration of miR-744 in HCC cells was statistically correlated with decrease of cell growth and restored G1 accumulation. Luciferase assay and Western blot analysis revealed that c-Myc is a direct target of miR-744. Down-regulation of miR-744 and up-regulation of c-Myc were detected in HCC specimens compared with adjacent normal tissues. Moreover, restoration of miR-744 rescues c-Myc induced HCC proliferation.Conclusions: Our data suggest that miR-744 exerts its tumor suppressor function by targeting c-Myc, leading to the inhibition of HCC cell growth. miR-744 may serve as a potentially useful target for the miRNA-based therapies of HCC in the future. © 2014 Lin et al.; licensee BioMed Central Ltd.


Zhang X.,Taizhou First Peoples Hospital | Xie J.,Taizhou First Peoples Hospital | Yu C.,Taizhou First Peoples Hospital | Yan L.,Taizhou First Peoples Hospital | Yang Z.,Taizhou First Peoples Hospital
Experimental and Therapeutic Medicine | Year: 2014

To evaluate the clinical significance of mRNA expression of cytokeratin 19 (CK19), epidermal growth factor receptor (EGFR) and lung-specific X protein (LUNX), a total of 42 patients who were diagnosed with non-small cell lung cancer (NSCLC) by pathology were studied retrospectively. The messenger RNA (mRNA) expression levels of CK19, EGFR and LUNX in the peripheral blood were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). The expression of CK19 mRNA did not differ significantly according to the location, size, clinical stage or differentiation of the primary tumor (all P>0.05). However, there was a significant difference in the level of CK19 mRNA expression between squamous carcinoma and adenocarcinoma. The positive rates of EGFR mRNA in the patient and the healthy control groups were 69.0 and 12.5%, respectively, and were significantly different (P<0.05). The positive rates of LUNX mRNA in the two groups were 40.5 and 0%, respectively, and were significantly different (P<0.05). The results indicate that the mRNA expression of CK19, EGFR and LUNX in the peripheral blood is of significant clinical value for the diagnosis of micrometastasis and the prognosis of lung cancer.


PubMed | Taizhou First Peoples Hospital
Type: | Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | Year: 2016

Lung cancer is one of the most common malignancies in the world and the most threatening cancer to human health. Effective therapies based on non-cytotoxic induction in cell inflammation- and apoptosis-responsive pathways are thought to represent a novel advance in treating lung cancer. However, many studies are still required for effective pharmaceutical to induce cancer cell death. Hyperoside (Hyp) is the chief component of some Chinese herbs with anticancer effect. Here, we investigated the role of hyperoside on the lung cancer cell migration, invasion, inflammation and apoptosis in A549 cells in vitro and xenografts of nude mice in vivo. A549 cells were injected in nude mice for establishing tumors. Our results showed that hyperoside suppressed the proliferation, migration and invasion. Additionally, apoptosis was induced by hyperoside via Bcl-2/Bax-regulated Caspase3 activation, suggesting that hyperoside might inhibit lung cancer progression through apoptotic induction. And also, hyperoside could prevent progression and development of lung cancer through inactivating NF-B signaling pathway. Subsequently, inflammatory cytokines, including TNF-, IL-6, IL-1 and IL-18, were down-regulated significantly. And animal experiments also illustrated that the tumor volume and weight were reduced after hyperoside administration, which was also through apoptosis induction and prevention of inflammation response by Caspase3 activation and NF-B inactivation. To our knowledge, it was the first time to evaluate the effects of hyperoside on preventing progression and development of lung cancer in vivo and in vitro to assess the possible therapies of hyperoside as a future approach for preventing lung cancer progression and development.

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