Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice / 中华医学杂志(英文版)

<p><b>Background</b>Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models.</p><p><b>Methods</b>We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group.</p><p><b>Results</b>We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 10/L at the 28 day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] μmol/L) at the 28 day, particularly those injected with 1.5 mg/kg NaYbF:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney.</p><p><b>Conclusion</b>The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.</p>

Rare-earth Nanoparticle-induced Cytotoxicity on Spatial Cognition Memory of Mouse Brain / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure.</p><p><b>METHODS</b>Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice.</p><p><b>RESULTS</b>Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain.</p><p><b>CONCLUSIONS</b>This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.</p>

Association between N-terminal proB-type Natriuretic Peptide and Depressive Symptoms in Patients with Acute Myocardial Infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>While depression and certain cardiac biomarkers are associated with acute myocardial infarction (AMI), the relationship between them remains largely unexplored. We examined the association between depressive symptoms and biomarkers in patients with AMI.</p><p><b>METHODS</b>We performed a cross-sectional study using data from 103 patients with AMI between March 2013 and September 2014. The levels of depression, N-terminal proB-type natriuretic peptide (NT-proBNP), and troponin I (TnI) were measured at baseline. The patients were divided into two groups: those with depressive symptoms and those without depressive symptoms according to Zung Self-rating Depression Scale (SDS) score. Baseline comparisons between two groups were made using Student's t-test for continuous variables, Chi-square or Fisher's exact test for categorical variables, and Wilcoxon test for variables in skewed distribution. Binomial logistic regression and multivariate linear regression were performed to assess the association between depressive symptoms and biomarkers while adjusting for demographic and clinical variables.</p><p><b>RESULTS</b>Patients with depressive symptoms had significantly higher NT-proBNP levels as compared to patients without depressive symptoms (1135.0 [131.5, 2474.0] vs. 384.0 [133.0, 990.0], Z = -2.470, P = 0.013). Depressive symptoms were associated with higher NT-proBNP levels (odds ratio [OR] = 2.348, 95% CI: 1.344 to 4.103, P = 0.003) and higher body mass index (OR = 1.169, 95% confidence interval [CI]: 1.016 to 1.345, P = 0.029). The total SDS score was associated with the NT-proBNP level (β= 0.327, 95% CI: 1.674 to 6.119, P = 0.001) after multivariable adjustment. In particular, NT-proBNP was associated with three of the depressive dimensions, including core depression (β = 0.299, 95% CI: 0.551 to 2.428, P = 0.002), cognitive depression (β = 0.320, 95% CI: 0.476 to 1.811, P = 0.001), and somatic depression (β = 0.333, 95% CI: 0.240 to 0.847, P = 0.001). Neither the overall depressive symptomatology nor the individual depressive dimensions were associated with TnI levels.</p><p><b>CONCLUSIONS</b>Depressive symptoms, especially core depression, cognitive depression, and somatic depression, were related to high NT-proBNP levels in patients with AMI.</p>

Analysis of relapse factors and risk assessment of adult acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the risk factors of acute lymphoblastic leukemia (ALL) recurrence in adult patients and establish a prognosis index (PI) calculation model in order to improve the prevention strategy of ALL in adults.</p><p><b>METHODS</b>104 adult ALL patients from Blood Diseases Hospital & Chinese Academy of Medical Sciences between August 2008 and November 2011 were enrolled. COX proportional hazards regression stratified by Dummy variable was used to set up the prediction model; Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. After calculated individual PI value, patients' expected survival should be estimated by groups.</p><p><b>RESULTS</b>The overall median survival of adult ALL patients was 22.00 months (95% CI 17.00-27.00). COX regression analysis showed that chemotherapy group patients had a higher risk of recurrence than of ASCT group while setting treatment as the dummy variable (RR=2.052, 95%CI 0.877-4.799, P=0.007). Stratified Analysis showed that the risk factors of B-ALL recurrence in adult patients included HGB <100 g/L (RR=0.186, 95% CI 0.068-0.512, P=0.001), CNSL (RR=7.767,95% CI 2.951- 20.433, P=0.001), number of consolidation chemotherapy<3 (RR=0.445, 95% CI 0.211-0.940, P=0.034) and Ph chromosome positive (RR=2.771, 95% CI 1.353-5.674, P=0.005). Grouped by the PI value, the expected survival of each individual patient could be estimated as PI=0.58 base.</p><p><b>CONCLUSION</b>HGB, CNSL, number of consolidation chemotherapy and Ph chromosome were independent risk factors of B-ALL recurrence in adult patients. PI value could predict the survival of adult ALL patients and provide reference for individual therapy and prognostic evaluation.</p>

Comparative analysis of Brucellosis epidemic between Shanxi province and the country / 中国地方病学杂志

Objective To analyze the Brucellosis incidence and to predict the trends of the disease in Shanxi province and the national in recent years,which could provide the reference for surveillance,prevention and control of the disease.Methods Brucellosis data which was reported monthly during January 2006 and December 2010 in Shanxi province and the data released by Chinese Center for Disease Control and Prevention during January 2005 and December 2010 were collected.Several indexes,such as the annual increasing number,the development rate,growth rate and other indicators were applied to compare Shanxi province with the national Brucellosis epidemic in recent years.What's more,the seasonal autoregressive integrated moving average model (ARIMA) was fitted respectively with the data of Brucellosis incident number reported monthly,so as to predict the prevalence status in the coming two years by verifying the fitting effect.Results Brucellosis prevalence of Shanxi province reached the peak in 2008,and the incidence number was 5397,which was 900 more than 2007.From the onset of decline after 2008,the prevalence decreased by 17.67％ (906/5128) in 2010.However,national incidence of Brucellosis kept increasing before 2009 and the prevalence increased rapidly from 2007 to 2008,and the growth rate reached 39.16％ (8442/21 560).Although the number of Brucellosis fell by 2041 cases in 2010 than in 2009,the rate of decline was only 5.14％(2041/37 734).The fastigium of Brucellosis was from May to July yearly whether Shanxi province or the country.The ARIMA models of Shanxi province and the nation were ARIMA [(1,0,1)(1,1,0)12] and ARIMA[(1,0,1)(0,1,1)12],respectively,according to the incidence numbers reported monthly.The fitting effect of models showed that the predicted values of the two models were both consistent with the actual situation and all predicted values fell within the 95％ confidence limits,which depicted that they both fitted well.The predicted values depict that the incidence of Brucellosis overall trend was basically stable in Shanxi province,while the numbers in the nation would increase in a small extent in 2011 and 2012.The fastigium of Brucellosis was still from May to July yearly.Conclusions Brucellosis control measures are effective in Shanxi province,incidence of Brucellosis declining.The ARIMA model could predict the number of Brucellosis well,which can provide a valuable reference for the predication and evaluation of Brucellosis epidemic in the future.