BackgroundIt is well-known that the treatment and monitoring methods are limited for advanced stage of endometrial carcinoma. Biological molecules with expression changes during tumor progression become potential therapeutic targets for advanced stage endometrial carcinoma. Annexin A2 (ANXA2) has been reported to be overexpressed in recurrent endometrial carcinoma, and the expression of human epididymis protein 4 (HE4) is upregulated in endometrial carcinoma. What’s more, ANXA2 and HE4 interacted in ovarian cancer and promoted the malignant biological behavior. We speculated that their interaction may exist in endometrial carcinoma as well. We evaluated the expression and the correlation relationship of ANXA2 and HE4 in endometrial carcinoma.MethodsThe expression of ANXA2 and HE4 protein in 84 endometrial carcinoma, 30 endometrial atypical hyperplasia, and 18 normal endometrial tissue samples were then measured using an immunohistochemical assay in paraffin embedded endometrial tissues. The structural relationship between ANXA2 and HE4 was explored by immunoprecipitation and double immunofluorescent staining.ResultsANXA2 and HE4 co-localized in both endometrial tissues and endometrial carcinoma cells. ANXA2 and HE4 were expressed in 95.2 % and 85.7 % of the the endometrial carcinoma, respectively, which were significantly higher than normal endometrium (55.6 % and 16.7 %, both p < 0.05). The expression of ANXA2 and HE4 was significantly correlated with FIGO stage, degree of differentiation, myometrial invasion, and lymph node metastasis. ANXA2 was an independent risk factor for the prognosis of endometrial carcinoma (p < 0.05, hazard ratio [HR] = 8.004). The expression of ANXA2 and HE4 was positively correlated (Spearman correlation coefficient = 0.228, p < 0.05). HE4 was an independent factor for ANXA2 in multivariate linear regression model (p < 0.05).ConclusionWe revealed the co-localization of ANXA2 and HE4 in endometrial carcinoma. Expression levels of ANXA2 and HE4 were closely related to the malignant biological behavior of endometrial carcinoma, and ANXA2 was an independent risk factor for poor prognosis. The expression of ANXA2 and HE4 can affect each other.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0208-8) contains supplementary material, which is available to authorized users.

The main aims of this study were to determine the expression of human epididymis protein 4 (HE4) in endometrial cancer and to explore the relationships between HE4 expression, clinicopathological parameters, and prognosis. Immunohistochemistry was used to detect HE4 expression in 102 cases of endometrial cancer, 30 cases of endometrial atypical hyperplasia, and 20 cases of normal endometrium. The positive expression rate of HE4 in endometrial carcinoma was 84.62%, significantly higher than 66.67% in atypical hyperplasia (P < 0.05) and 15.00% in normal endometrium (P < 0.0.01). With the exception of stage II, HE4 expression in endometrial cancer showed an increasing tendency with increased clinical stage (P < 0.05). The positive expression rate of HE4 increased with a decrease in the degree of differentiation. A statistically significant difference was observed between the highly differentiated group and the poorly differentiated group (P < 0.05). Mortality in endometrial cancer patients with high HE4 expression was significantly higher than that in patients with low HE4 expression (P < 0.05). Endometrial cancer patients with high HE4 expression have a poor prognosis.

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IntroductionInfective endocarditis (IE) presents with increasing incidence and mortality in some regions and countries, as well as serious socioeconomic burden. The current study aims to compare and interpret the IE burden and temporal trends globally and in different regions from 1990 to 2019.MethodsData on the incidence, deaths and disability-adjusted life years (DALYs) caused by IE were extracted and analyzed from the Global Burden of Disease Study 2019. Estimated annual percentage changes (EAPC) were adopted to quantify the change trends of age-standardized rates (ASRs). Besides, potential contributors of serious IE burden were also evaluated including age, gender, social-demographic index (SDI), and age-standardized incident rate (ASIR) in 1990.ResultsGlobally, the number of IE cases and deaths has increased sharply during the past 30 years from 478,000 in 1990 to 1,090,530 in 2019 and from 28,750 in 1990 to 66,320 in 2019, and both presented an upward temporal trend annually (EAPC:1.2 for incidence and 0.71 for death). However, the EAPC of age-standardized DALYs demonstrated a negative temporal trend despite increasing DALYs from 1,118,120 in 1990 to 1,723,590 in 2019. Moreover, older patients and men were more severely affected. Meanwhile, different SDI regions had different disease burdens, and correlation analyses indicated that SDI presented a positive association with ASIR (R = 0.58, P &lt; 0.0001), no association with age-standardized death rate (R = −0.06, P = 0.10), and a negative association with age-standardized DALYs (R = −0.40, P &lt; 0.0001). In addition, the incidence of IE increased in most countries during the past 30 years (190 out of 204 countries). However, the change trends of deaths and DALYs were heterogeneous across regions and countries. Finally, we discovered positive associations of the EAPC of ASRs with the SDI in 2019 among 204 countries and territories but few associations with the ASIR in 1990.ConclusionGenerally, the global burden of IE is increasing, and there is substantial heterogeneity in different genders, ages and regions, which may help policy-makers and medical staff respond to IE and formulate cost-effective interventional measures.

PurposeCisplatin plus gemcitabine (GEM) is a standard regimen for the first-line treatment of advanced non-small cell lung cancer. The aim of this study was to prepare biocompatible and biodegradable polymeric prodrugs and construct nanoparticles (NPs) with layer-by-layer (LbL) technique.MethodsPlatinum (Pt) (IV) complex with a carboxyl group was conjugated to the amino group of chitosan (CH), resulting in a CH-Pt conjugation with positive charge. GEM with amino group was conjugated to the carboxyl group of hyaluronic acid (HA), resulting in a HA-GEM conjugation with negative charge. Novel LbL NPs consisting of the CH-Pt core and the HA-GEM layer, named as HA-GEM/CH-Pt NPs, were constructed. The physicochemical properties of the HA-GEM/CH-Pt NPs were investigated. In vitro cytotoxicity against human non-small lung cancer cells (NCl-H460 cells) was investigated, and in vivo antitumor efficiency was evaluated on mice bearing NCl-H460 cells xenografts.ResultsHA-GEM/CH-Pt NPs have a size of about 187 nm, a zeta potential value of −21 mV and high drug encapsulation efficiency of 90%. The drug release of HA-GEM/CH-Pt NPs exhibited a sustained behavior. HA-GEM/CH-Pt NPs could significantly enhance in vitro cytotoxicity and in vivo antitumor effect against lung cancer animal model compared to the single-drug-loaded NPs and free drug solutions.ConclusionThe results demonstrated that the HA-GEM/CH-Pt NPs might be a promising system for the synergetic treatment of lung carcinoma.

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Background: Coronavirus disease 2019 can result in myocardial injury in the acute phase. However, information on the late cardiac consequences of coronavirus disease 2019 (COVID-19) is limited.Methods: We conducted a prospective observational cohort study to investigate the late cardiac consequences of COVID-19. Standard echocardiography and myocardial strain assessment were performed, and cardiac blood biomarkers were tested in 86 COVID-19 survivors 327 days (IQR 318–337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients.Results: There were no significant differences in all echocardiographic structural and functional parameters, including left ventricular (LV) global longitudinal strain, right ventricular (RV) longitudinal strain, LV end-diastolic volume, RV dimension, and the ratio of peak early velocity in mitral inflow to peak early diastolic velocity in the septal mitral annulus (E/e') among COVID-19 survivors, healthy controls and risk factor-matched controls. Even 26 patients with myocardial injury at admission did not have any echocardiographic structural and functional abnormalities. There were no significant differences among the three groups with respect to serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI).Conclusion: This study showed that COVID-19 survivors, including those with myocardial injury at admission and those with severe and critical types of illness, do not have any echocardiographic evidence of cardiac structural and functional abnormalities 327 days after diagnosis.

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