Mercaptopyrimidine-templated gold nanoclusters for antithrombotic therapy.

Here we report for the first time that mercaptopyrimidine-templated gold nanoclusters (DAMP-AuNCs) can be used as a novel anticoagulant candidate for the design of antithrombotic drugs. Anticoagulant mechanisms revealed that DAMP-AuNCs significantly inhibited thrombus formation by interacting with fibrinogen. Carrageenan-induced mice tail thrombosis model experiments showed that DAMP-AuNCs had antithrombotic efficacy comparable to heparin in vivo. More importantly, these ultrasmall AuNCs possess excellent blood compatibility and only induce negligible bleeding side effects. Our study is a successful attempt at developing novel antithrombotic agents with high biosafety.

A consensus on the management of allergy in kindergartens and primary schools / 中国学校卫生

Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Thermoelectric Material SnPb2Bi2S6: The 4,4L Member of Lillianite Homologous Series with Low Lattice Thermal Conductivity.

Although the binary sulfides Bi2S3, PbS, and SnS have attracted extensive interest as thermoelectric materials, no quaternary sulfides containing Sn/Pb/Bi/S elements have been reported. Herein, we report the synthesis of a new quaternary sulfide, SnPb2Bi2S6, which crystallizes in the orthorhombic space group Pnma with unit cell parameters of a = 20.5458(12) Å, b = 4.0925(4) Å, c = 13.3219(10) Å. SnPb2Bi2S6 has a lillianite-type crystal structure consisting of two alternately aligned NaCl-type structural motifs separated by a mirror plane of PbS7 monocapped trigonal prisms. In the lillianite homologous series, SnPb2Bi2S6 can be classified as 4,4L, where the superscripted numbers indicate the maximum numbers of edge-sharing octahedra in the two adjacent NaCl-shaped slabs along the diagonal direction. The obtained SnPb2Bi2S6 phase exhibited good thermal stability up to 1000 K and n-type degenerate semiconducting behavior, with a power factor of 3.7 µW cm-1 K-2 at 773 K. Notably, this compound exhibited a very low lattice thermal conductivity of 0.69-0.92 W m-1 K-1 at 300-1000 K. Theoretical calculations revealed that the low thermal conductivity is caused by the complex crystal structure and the related elastic properties of a low Debye temperature, low phonon velocity, and large Grüneisen parameters. A reasonable figure of merit (ZT) of ∼0.3 was obtained at 770 K.

Analysis of allogeneic hematopoietic stem cell transplantation with high-dose cyclophosphamide-induced immune tolerance for severe aplastic anemia.

The study was aimed to explore the efficacy and safety of allo-HSCT with high-dose cyclophosphamide-induced immune tolerance for SAA. In the present study, 20 cases (12 male, 8 female; average age = 17.8 years) received reduced-intensity conditioning allo-HSCT from August 2012 to August 2014 in the Beijing Military Region General Hospital. All were HLA mismatched and received CSA; 11 received ATG-intensive immune therapy. Donors underwent mobilization with cell colony-stimulating factor. The modified preconditioning regimen included reduced-strength fludarabine combined with Busulfex and cytarabine, cyclophosphamide. Cyclophosphamide (50 mg/kg/d) induced immune tolerance 3 days after transplantation and was combined with immunosuppressive agents, including CSA, MTX, and FK506, for GVHD prophylaxis and the management of observed toxicity, GVHD and DFS. Hematopoietic reconstitution was achieved in 17 cases and engraftment after a second transplantation in an additional three cases. The average times to engraftment were 17.4 and 21.3 days, respectively, with neutrophils ≥0.5 × 109/L and platelets ≥20 × 109/L. Engraftment was confirmed by the evidence of 100 % donor hematopoiesis; T lymphocyte subset counts also increased significantly after transplantation. During follow-up monitoring to April 2015 (median duration = 17.7 months), three patients died of complications, while the other 17 showed disease-free survival (DFS rate = 85 %; longest DFS period = 32 months). Reduced-intensity allo-HSCT with high-dose cyclophosphamide-induced immune tolerance treatment is effective for SAA and can be the key technology extensively used in clinic, but its efficacy needs to be confirmed further with prospective randomized study with increased sample size.

Effect of overexpression of hypoxia-inducible factor-1α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate.

OBJECTIVE: To study effect of overexpression of hypoxia-inducible factor-1α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate. METHODS: The prostate cancer LNCaP cells were inoculated in the abdomen of mice. All the mice were randomly placed in the gas chamber with different oxygen content. The groups were divided as follows: twelve mice in hypoxia group, sixteen mice in normoxia group, ten mice in hyperoxia group. After 28 d of treatment, the mice were weighed, the blood samples were taken from the left ventricle, and the tumor was isolated and weighed. Tumor growth, angiogenesis and vascularization, HIF-1α expression and intracellular signal transduction molecules expression in each group of xenografts were detected and analyzed by using Western blotting and immunofluorescence and determination of hemoglobin. RESULTS: Comparison of the growth of xenografts in each group showed that, the xenografts growth of hypoxia group was more quickly than that of normoxia group. The difference was statistically significant (P = 0.004). The difference in xenografts growth between hyperoxia group compared and normoxia group was not statistically significant (P > 0.05). The expressions of HIF-1α, VEGF and VEGF-R of xenografts in hyperoxia group were significantly higher than those of normoxia group (P < 0.05). The expression of HIF-1α of xenografts in hypoxia group and normoxia group were similar. The blood growth rate of xenografts in hypoxia group (170%) was significantly higher than that of normoxia group (40%) (P < 0.05). The expression of Nrf2 of xenografts in hyperoxia group was significantly higher than that of normoxia group (P < 0.05). CONCLUSIONS: When hyperoxia induces the overexpression of HIF-1α in LNCaP tumor, it will not affect tumor growth. It provides a new ideas and theoretical basis for the clinical treatment of prostate cancer.

Intensive insulin therapy increases sex hormone-binding globulin in newly diagnosed type 2 diabetic patients.

OBJECTIVE: Many studies have shown that low sex hormone-binding globulin (SHBG) is associated with insulin resistance, but only few studies have examined how serum SHBG is regulated by insulin in humans. This interventional study aimed to investigate the effect of insulin therapy (IT) on serum SHBG levels in newly diagnosed type 2 diabetic patients. METHODS: A total of 80 newly diagnosed type 2 diabetic subjects were enrolled and randomly grouped into a 2-week intensive IT with/without metformin. Serum SHBG, total testosterone, glucose, liver enzymes, lipids, insulin, and C-peptide levels were measured before and after IT. RESULTS: Before IT, serum SHBG levels were negatively correlated with BMI, waist circumference (WC), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), triglyceride (TG), fasting insulin, and C-peptide, and homeostatic model assessment of insulin resistance (HOMA-IR), and positively with HDL-C (all P for trend <0.05), after adjustment for age and sex. IT increased serum SHBG levels from 26.5±14.5 to 33.2±15.0 nmol/l (P<0.001), increased by 25.2% (95% CI, 20.3 to 30.9%, P<0.001). In a multiple linear regression model adjusting for age, sex, BMI, and WC, the decreases in ΔALT (standardized regression coefficient ß=-0.374, P=0.012) and ΔTG (ß=-0.380, P=0.020) were independent contributors to the increase in ΔSHBG. CONCLUSIONS: IT increases serum SHBG likely through improving insulin resistance and liver function.

Low serum sex hormone-binding globulin is associated with nonalcoholic fatty liver disease in type 2 diabetic patients.

INTRODUCTION: Studies have indicated that low serum sex hormone-binding globulin (SHBG) and testosterone levels are associated with nonalcoholic fatty liver disease (NAFLD). However, it remains unclear whether an association exists between SHBG and NAFLD independent of testosterone. OBJECTIVE: This study was aimed to investigate the relationship between SHBG and both total and free testosterone levels with NAFLD. SUBJECTS AND MEASURES: One hundred and twenty patients with NAFLD and 120 age-, sex- and BMI-matched patients with non-NAFLD were enrolled into a case-control study. Serums SHBG, total testosterone (TT), liver enzymes, lipids, insulin, C-peptide and plasma glucose were measured. Free testosterone (FT) and fatty liver index were calculated. RESULTS: Serum SHBG levels were significantly lower in NAFLD group than in non-NAFLD group (24·5 ± 11·0 vs 37·6 ± 14·4 nm, P < 0·001). After adjustment for age, smoking status, alcohol use, duration of diabetes, BMI and fasting C-peptide, serum SHBG levels in men and women were inversely associated with NAFLD, with odds ratio (OR) and 95% confidence interval (CI) in the forth quartile as 0·05 (0·01-0·30) and 0·25 (0·08-0·77) compared with the first quartile (OR = 1·00). Additional adjustment for TT in men and FT in women did not materially alter the association. The relationship between serum TT (for men) and FT (for women) with NAFLD was attenuated and even diminished after multivariable adjustment for known risk factors and SHBG. CONCLUSION: Low serum SHBG levels, but not TT or FT, are associated with NAFLD in type 2 diabetic patients.