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PBX3 (Pre-B-cell leukemia homeobox 3) had been considered to be a multifunctional oncogene which involved in tumor growth, invasion, and metastasis in leukemia and some solid tumors. However, the contribution of PBX3 to papillary thyroid carcinoma (PTC) remains unclear. In this study, we found that PBX3 expression was significantly upregulated in PTC tissues compared to adjacent normal tissues, and high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis of PTC patients. Overexpression of PBX3 in PTC cell lines promoted cell proliferation. Consistently, knockdown of PBX3 by shRNA induced cell cycle arrest at G0/G1 phase, and inhibited angiogenesis and tumor growth in vitro and in vivo. Furthermore, PBX3 promoted PTC cell proliferation and angiogenesis through activation of AT1R/VEGFR2 pathway while overexpression of AT1R and treatment with VEGFA reversed PBX3-shRNA-induced decreased phosphorylation of VEGFR2 and its downstream (ERK1/2, AKT and Src). It demonstrated that PBX3 could be used as a potential prognostic biomarker and therapeutic target for PTC.

Papillary thyroid carcinoma (PTC) is the most common subtype of differentiated thyroid cancers in Asian coastal cities, where the patients have increased risk of potentially high or excessive iodine intake. Given the high metastasis and recurrence of patients with BRAFV600E mutation, the mortality rate of thyroid cancer has recently shown an upward trend. A variety of therapies, including surgery, radiotherapy, and chemotherapy, have been used to treat thyroid cancer, but these therapies still have limitations, including postoperative complications, drug resistance, poor efficacy, or serious side effects. Recent studies have shown the potential of active ingredients derived from herbal medicine in inhibiting PTC via various cell signaling pathways. Some plant-derived compounds, such as apigenin, genistein, and curcumin, are also known to prevent and treat PTC. This article summarizes the recent advances in the structure-functional impact of anti-PTC active ingredients and their effects on PTC cells and tumor microenvironments with an emphasis on their challenges from basic research to clinical practice.

The platelet-derived growth factor (PDFG) signaling pathway exerts persistent activation in response to a variety of stimuli and facilitates the progression of hepatic fibrosis. Since this pathway modulates a broad spectrum of cellular processes, including cell growth, differentiation, inflammation and carcinogenesis, it has emerged as a therapeutic target for hepatic fibrosis and liver-associated disorders. The present review exhibits the current knowledge of the role of the PDGF signaling pathway and its pathological profiles in hepatic fibrosis, and assesses the potential of inhibitors which have been investigated in the experimental hepatic fibrosis model, in addition to the clinical challenges associated with these inhibitors.

We aimed to determine the relationship between lower extremity peripheral arterial disease (PAD), 10-year coronary heart disease (CHD), and stroke risks in patients with type 2 diabetes (T2DM) using the UKPDS risk engine. We enrolled 1178 hospitalized T2DM patients. The patients were divided into a lower extremity PAD group (ankle-brachial index≤0.9 or >1.4; 88 patients, 7.5%) and a non-PAD group (ankle-brachial index>0.9 and ≤1.4; 1090 patients, 92.5%). Age; duration of diabetes; systolic blood pressure; the hypertension rate; the use of hypertension drugs, ACEI /ARB, and statins; CHD risk; fatal CHD risk; stroke risk; and fatal stroke risk were significantly higher in the PAD group than in the non-PAD group (P<0.05 for all). Logistic stepwise regression analysis indicated that ABI was an independent predictor of 10-year CHD and stroke risks in T2DM patients. Compared with those in the T2DM non-PAD group, the odds ratios (ORs) for CHD and stroke risk were 3.6 (95% confidence interval (CI), 2.2–6.0; P<0.001) and 6.9 (95% CI, 4.0–11.8; P<0.001) in those with lower extremity PAD, respectively. In conclusion, lower extremity PAD increased coronary heart disease and stroke risks in T2DM.

Background: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD). However, the association between CKD and CVD risk in patients with type 2 diabetes mellitus (T2DM) in China has not yet been well investigated. This study aimed to determine the association of CKD with the risks of coronary heart disease (CHD) and stroke in a Chinese population with T2DM. Methods: A total of 1401 inpatients with T2DM at the Second Affiliated Hospital of Zhejiang University School of Medicine between April 2008 and November 2013 were included in this study. The CKD-Epidemiology Collaboration equation for Asians was used to classify CKD. The UK Prospective Diabetes Study risk engine was used to estimate the risks of CHD and stroke. Results: CHD risk was significantly increased with CKD stage (20.1%, 24.8%, and 34.3% in T2DM patients with no CKD, CKD Stage 1–2, and Stage 3–5, respectively; P < 0.001 for all). The stroke risk was also increased with CKD stage (8.6%, 12.7%, and 25.4% in T2DM patients with no CKD, CKD Stage 1–2, and Stage 3–5, respectively; P < 0.001 for all). Compared with no-CKD group, the odds ratios (ORs) for high CHD risk were 1.7 (P < 0.001) in the CKD Stage 1–2 group and 3.5 (P < 0.001) in the CKD Stage 3–5 group. The corresponding ORs for high stroke risk were 1.9 (P < 0.001) and 8.2 (P < 0.001), respectively. Conclusion: In patients with T2DM, advanced CKD stage was associated with the increased risks of CHD and stroke. Key words: Chronic Kidney Disease; Coronary Disease; Stroke; Diabetes Mellitus

Circulating exosomal microRNAs (exomiR) have been demonstrated to be novel diagnostic biomarkers for various cancers. In this study, we found that circulating exomiR-1229 levels were significantly increased in the serum exosomes of patients with colorectal cancer (CRC) and significantly associated with tumor size, lymphatic metastasis, TNM stage and poor survival. Treatment with siRNA-Drosha, siRNA-ALIX and GW4869 repressed the expression of exomiR-1229 secreted from CRC cells. Both CRC-derived exosomes and exomiR-1229 mimic promoted the tubulogenesis of HUVECs, but transfection with exomiR-1229 inhibitor anta-miR-1229 significantly suppressed tube formation. Subsequently, HIPK2 was identified as a target of exomiR-1229 and responsible for the effect of exomiR-1229 on angiogenesis of HUVECs. ExomiR-1229 inhibited the protein expression of HIPK2, thereby activating VEGF pathway. Finally, anta-miR-1229 effectively inhibited tumor growth and angiogenesis in the nude mouse xenograft model. These results highlighted a novel mechanism of CRC angiogenesis and the biological roles of exomiR-1229.

Coronary heart disease (CHD) and stroke are common complications of type 2 diabetes mellitus (T2DM). We aimed to explore the differences in the risks of CHD and stroke between Chinese women and men with T2DM and their association with metabolic syndrome (MS). This study included 1514 patients with T2DM. The Asian Guidelines of ATPIII (2005) were used for MS diagnosis, and the UKPDS risk engine was used to evaluate the 10-year CHD and stroke risks. Women had lower CHD risk (15.3% versus 26.3%), fatal CHD risk (11.8% versus 19.0%), stroke risk (8.4% versus 10.3%), and fatal stroke risk (1.4% versus 1.6%) compared with men with T2DM (p<0.05–0.001). The CHD risk (28.4% versus 22.6%, p<0.001) was significantly higher in men with MS than in those without MS. The CHD (16.2% versus 11.0%, p<0.001) and stroke risks (8.9% versus 5.8%, p<0.001) were higher in women with MS than in those without MS. In conclusion, our findings indicated that Chinese women with T2DM are less susceptible to CHD and stroke than men. Further, MS increases the risk of both these events, highlighting the need for comprehensive metabolic control in T2DM.

Astragalus, a commonly used traditional Chinese medicine, has exhibited antitumor actions in patients. In this study, in vitro and in vivo antitumor effects of astragalus and synergistic antitumor efficacy in combination with pterostilbene were investigated. Melanoma cells were treated with pterostilbene (Pt), graduated doses of astragalus injection (AI), or these in combination. Cell viability was measured using a MTT assay. Released nucleosomes and caspase activity were measured using enzyme-linked immunosorbent assay. Growth inhibition in vitro and in vivo was also assessed. Analysis of variance and t tests were used for statistical analysis. Significant reduction (p

Objective. The association between thyroid nodule (TN) prevalence and metabolic syndrome (MetS) has only rarely been examined in iodine-adequate areas and needs further clarification. We investigated correlations between MetS and TN prevalence in the iodine-adequate area of Hangzhou, China.Material and Method. A cross-sectional study that screened and recruited individuals for cohort research 3 years later. The 13522 subjects (8926 men, 4596 women) were screened in 2009 for all MetS components, thyroid ultrasound (US), and thyroid function. Cohort research recruited 1610 subjects who were screened in both 2009 and 2012, of whom 1061 underwent follow-up research.Results. The prevalence of TN was higher in the MetS (+) group than in the MetS (−) group (χ2= 69.63,P< 0.001) and higher in women than in men (χ2= 11.65,P= 0.001). Waist circumference (WC) was positively related to the prevalence of TN (OR = 1.022,P< 0.001). Individuals with greater WC in 2009 were more likely to suffer from TN in 2012 (RR = 1.434,P= 0.024). Elevated triglyceride level was a risk factor for developing new TN (RR = 1.001,P= 0.035).Conclusion. Both greater WC and elevated triglycerides are risk factors for new TN in this iodine-adequate area in China.

A major polysaccharide fraction (PMPP) was obtained by purifying the crude polysaccharides extracted from Polygoni Multiflori Radix Praeparata . Preliminary structural characterization was conducted by physicochemical property and Fourier transform infrared spectroscopy. Monosaccharide component analysis indicated that PMPP was composed of rhamnose, arabinose, xylose and glucose in a molar ratio of 1.64:1.00:1.34:6.06. Intraperitoneal administration of PMPP could increase levels of serum IL-2 and hematological parameters (red blood cells, white blood cells and platelet counts), enhance antioxidant profiles, and promote hematopoiesis of splenocytes though up-regulating expressions of EPOR and GATA-1 proteins in cyclophosphamide (Cy) induced anemic mice. These findings indicate that PMPP played an important role in the protection against myelosuppression and immunosuppression in Cy-treated mice and may warrant further evaluation as a potential immunomodulatory agent.

Summary Objective Because of rapid alterations in lifestyle and the incidence of metabolic syndrome (MetS), the prevalence of carotid atherosclerosis (CA) and carotid plaque (CP) may increase in China. We aimed to evaluate the prevalence of CA and CP as well as its relation to MetS in an East Chinese population. Methods The study included 6142 subjects who underwent general health screening including carotid ultrasonography in 2009. Diagnoses of MetS were made according to the revised Adult Treatment Panel III criteria. Results The prevalence of CA and CP increased gradually with age. These conditions were more prevalent in men than in women (CA: 22·1%vs 12·0%, P

Carotid atherosclerosis (CA) and carotid plaque (CP) are highly correlated with cardiovascular disease. We aimed to determine the prevalence of CA and CP and their relationship with 10-year risks of stroke and coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM). We studied 1584 T2DM patients aged 20 years and older. CA and CP were detected using ultrasonography. Ten-year stroke and CHD risk were determined using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. The prevalence of CA and CP increased gradually with age. Men had a higher prevalence of CA than women (CA: 58.18% vs 51.54%, P

Because of rapid alterations in lifestyle and the incidence of metabolic syndrome (MetS), the prevalence of carotid atherosclerosis (CA) and carotid plaque (CP) may increase in China. We aimed to evaluate the prevalence of CA and CP as well as its relation to MetS in an East Chinese population.The study included 6142 subjects who underwent general health screening including carotid ultrasonography in 2009. Diagnoses of MetS were made according to the revised Adult Treatment Panel III criteria.The prevalence of CA and CP increased gradually with age. These conditions were more prevalent in men than in women (CA: 22.1%vs 12.0%, P0.001; CP: 12.6%vs 7.2%, P0.001). Multivariate logistic regression analysis showed that male gender, age, blood pressure, fasting blood glucose (FBG) and low-density lipoprotein cholesterol were risk factors for CA and CP, while high-density lipoprotein cholesterol was protective for CA. Age ≥ 50 years has the largest impact on CA and CP, followed by elevated blood pressure and elevated blood glucose. Individuals with MetS had a higher prevalence of CA (27.7%vs 20.0% in men, 24.0%vs 10.3% in women; P0.001 in both) and CP (16.6%vs 11.2% in men, P0.001; 11.8%vs 6.5% in women, P0.005) than those without MetS. The prevalence and odds ratios of CA and CP aggregated with an increasing number of MetS components, even in individuals exhibiting only one component.These results indicate that CA and CP have become a major public health problem in China. MetS and its components were associated with an increased prevalence of CA and CP.

To investigate the value of metalloproteinase-3 (MMP-3) levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis (AS).The serum and synovial fluid levels of MMP-3 were measured by enzyme linked immunosorbent assay (ELISA) in 48 patients with AS in week 0, 6 and 12; and also measured in 30 serum samples and 10 synovial fluid samples from healthy controls.The serum levels of MMP-3 in AS patients were significantly higher than those in controls. In AS patients, the MMP-3 levels in synovial fluid were significantly higher than those in serum levels. The serum MMP-3 levels in AS patients with peripheral arthritis were higher than those with exclusively axial involvement; while C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) did not differ between these 2 groups of AS. At week 6 and week 12 of etanercept treatment, the serum MMP-3 levels were significantly decreased (p0.01) with the declining trend of ESR, CRP, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) (all p0.01). Before the etanercept treatment (week 0), serum levels of MMP-3 were correlated with ESR, CRP, BASDAI and BASFI (p0.05). ESR was also correlated with CRP and BASFI, but not with BASDAI (r=0.361, P=0.071). At weeks 12, serum MMP-3 levels were still correlated with ESR, CRP and BASDAI (P0.05), but not with BASFI (P=0.339); ESR was correlated with CRP, but not with BASDAI and BASFI. There was a significant correlation between BASDAI and BASFI (r=0.818,P=0.001).Serum MMP-3 levels are closely related to disease activity and may serve as an useful indicator for efficacy of etanercept treatment in AS patients.

Background Platelet-monocyte aggregates (PMA) and C-reactive protein (CRP) are increased in unstable coronary disease. The interrelation of PMA with platelet activation, systemic inflammation, and their association with markers of myocardial injury has not been studied extensively. Hypothesis The study was undertaken to evaluate the association of CRP, PMA, and cardiac troponin I (cTnI) in patients admitted with non-ST elevation acute coronary syndromes (NSTE-ACS). Methods In all, 69 consecutive patients with NSTE-ACS, 58 patients with stable angina pectoris (SAP), and 46 control patients without coronary artery disease were selected; PMA, sP-selectin, sCD40L inter leukin, (IL)-6, CRP, and cTnI concentrations were measured in these patients at the time of admission. Patients with NSTE-ACS were classified into two groups: those with troponin normal (cTnI < 0.06 ng/ml) and those with troponin elevation (cTnI ≥ 0.06 ng/ml). Their risk for clinical in-hospital cardiac events (death and nonfatal myocardial infarction) was analyzed. Results Compared with SAP and control, patients with NSTE-ACS exhibited higher levels of PMA, sP-selectin, sCD40L, IL-6, and CRP. All these parameters were found to be higher (p < 0.001 ) in patients with troponin elevation than in those with normal troponin. There was a significant relationship between PMA and CRP (r =0.628, p < 0.001) and cTnI (r = 0.557, p < 0.001) in patients with NSTE-ACS. Logistic analysis further demonstrated that the presence of elevated PMA, CRP, and cTnI levels each confers and increases risk of future cardiac events. Conclusions Levels of PMA and CRP were significantly increased in patients with NSTE-ACS, especially in those with troponin elevation. This increase is strongly related to the risk of in-hospital cardiac events. A panel of PMA, CRP, and cTnI may provide important information additional to current laboratory data for the treatment of NSTE-ACS. Copyright © 2007 Wiley Periodicals, Inc.

To construct the eukaryotic expression plasmid containing mouse vasoactive intestinal peptide(VIP) gene with biological activities.VIP cDNA including the sequences of signal peptide was cloned from mouse thymus by RT-PCR, and then inserted into the mammalian expression vector pcDNA3.1 between Hind III and EcoR I restriction sites. COS-7 cells were transfected with pcDNA3. 1-VIP using liposome, the expression of VIP was identified by Western blot and ELISA. Supernatant of transfected cell culture was added to LPS-stimulated macrophages and the TNF-alpha production in cell medium was observed by ELISA.The cloned VIP cDNA was confirmed by enzyme digestion and DNA sequencing. The expression of VIP was detected in the pcDNA3. 1-VIP transfected COS-7 cells by Western blot and ELISA. The VIP in culture supernatant potently inhibited TNF-alpha production by LPS-induced Macrophages in vitro.The eukaryotic expression plasmid that expresses biological active murine VIP has been constructed successfully.

To explore the relationship between risk factors for coronary heart disease (CHD) and coronary artery lesions.Potential risk factors were studied in 341 patients underwent coronary angiography.(1) Coronary angiography showed coronary artery lesions in 214 patients (lesion group), and no lesion in 127 patients (non-lesion group). There was significant difference in age, past history of diabetes, family history of CHD, smoking history, high-density lipoprotein cholesterol (HDL-C), lower-density lipoprotein cholesterol (LDL-C), ratio of total cholesterol to HDL-C (TC/HDL-C), lipoprotein(a) [Lp(a)], fibrinogen (Fbg) and high-sensitivity C-reactive protein (hs-CRP) between two groups (P0.05). (2) There was significant correlation between severity of coronary artery lesions and hs-CRP, Lp(a), TC/HDL-C, Fbg, hyperlipidemia, TC, LDL-C and TG (with coefficients of correlation of 0.338, 0.250, 0.241, 0.207, 0.167, 0.147, 0.140 and 0.139; respectively, P0.05). (3) Analysis of receiver operating characteristics (ROC) curve for patients with coronary angiography and risk factors for CHD showed that the areas under ROC curve were 0.810, 0.669, 0.626, 0.625, 0.619 and 0.618 for hs-CRP, TC/HDL-C, Lp(a), Fbg, LDL-C and past history of hyperlipidemia, respectively.Past history of hyperlipidemia was a predictor for occurrence of CHD. Ratio of TC/HDL-C and blood level of Lp(a) could be used as predictors in screening for high blood lipid, which were much stronger than others. It is suggested that hs-CRP had an excellent predictive value in current coronary inflammatory lesions.