Objectives The purpose of this study was to investigate the treatment effect and molecular mechanism of tetrahedral framework nucleic acids (tFNAs), novel self‐assembled nucleic acid nanomaterials, in diffuse BMEC injury after SAH. Materials and Methods tFNAs were synthesized from four ssDNAs. The effects of tFNAs on SAH‐induced diffuse BMEC injury were explored by a cytotoxicity model induced by hemin, a breakdown product of hemoglobin, in vitro and a mouse model of SAH via internal carotid artery puncture in vivo. Cell viability assays, wound healing assays, transwell assays, and tube formation assays were performed to explore cellular function like angiogenesis. Results In vitro cellular function assays demonstrated that tFNAs could alleviate hemin‐induced injury, promote angiogenesis, and inhibit apoptosis in hemin cytotoxicity model. In vivo study using H&E and TEM results jointly indicated that the tFNAs attenuate the damage caused by SAH in situ, showing restored number of BMECs in the endothelium layer and more tight intercellular connectivity. Histological examination of SAH model animals confirmed the results of the in vitro study, as tFNAs exhibited treatment effects against diffuse BMEC injury in the cerebral microvascular bed. Conclusions Our study suggests the potential of tFNAs in ameliorating diffuse injury to BMECs after SAH, which laid theoretical foundation for the further study and use of these nucleic acid nanomaterials for tissue engineering vascularization.

The studies were carried out on nude mice bearing human colorectal carcinoma SW480 cell line xenografts to evaluate the chemotherapeutic potential of selenium containing compounds such as sodium selenite (SSe) and selenomethionine (SeMet). Three doses of anticancer drugs were used, including 0.1 mg/kg/day SSe (LSSe), 2 mg/kg/day SSe (HSSe), and 2 mg/kg/day SeMet. We explored the anticancer effect of SSe and SeMet administered by IP injection for 21 days. We observed the pathologic changes and the cell apoptosis in tumor tissue by HE staining and TUNNEL assay after HSSe and SeMet treatment. GSH level and antioxidant enzyme GPX activity in tumor tissues were assessed. In addition, Western blotting was used to detect the expression of apoptosis-related proteins. The results suggested that HSSe and SeMet had significantly inhibited tumor growth in vivo. We also observed the pathologic changes and cell apoptosis in tumor tissues after HSSe and SeMet treatment. GSH level was a bit increased but the GPX activity was reduced. Moreover, SSe and SeMet treatment downregulated the expression of the protein Bcl-xL, increased the expression of Bax, Bad, and Bim, and activated caspase-9. SSe and SeMet may be the selective, low-toxic anticancer agents to treat human colorectal carcinoma cancer.

PurposeTo evaluate midazolam sequential with dexmedetomidine for agitated patients undergoing weaning to implement light sedation in ICU.MethodsThis randomized, prospective study was conducted in Tianjin Third Central Hospital, China. Using a sealed-envelope method, the patients were randomly divided into 2 groups (40 patients per group). Each patient of group A received an initial loading dose of midazolam at 0.3–3 mg/kg·h 24 h before extubation, followed by an infusion of dexmedetomidine at a rate of 0.2–1 μg/kg·h until extubation. Each patient of group B received midazolam at a dose of 0.3–3 mg/kg·h until extubation. The dose of sedation was regulated according to RASS sedative scores maintaining in the range of -2-1. All patients were continuously monitored for 60 min after extubation. During the course, heart rate (HR), mean artery pressure (MAP), extubation time, adverse reactions, ICU stay, and hospital stay were observed and recorded continuously at the following time points: 24 h before extubation (T1), 12 h before extubation (T2), extubation (T3), 30 min after extubation (T4), 60 min after extubation (T5).ResultsBoth groups reached the goal of sedation needed for ICU patients. Dexmedetomidine was associated with a significant increase in extubation quality compared with midazolam, reflected in the prevalence of delirium after extubation (20% (8/40) vs 45% (18/40)), respectively (p = 0.017). There were no clinically significant decreases in HR and MAP after infusing dexmedetomidine or midazolam. In the group A, HR was not significantly increased after extubation; however, in the group B, HR was significantly increased compared with the preextubation values (p < 0.05). HR was significantly higher in the group B compared with the group A at 30 and 60 min after extubation (both, p < 0.05). Compared with preextubation values, MAP was significantly increased at extubation in the group B (p < 0.05) and MAP was significantly higher at T3, T4, T5 in the group B than group A (p < 0.05). There was a significant difference in extubation time ((3.0 ± 1.5) d vs (4.3 ± 2.2) d, p < 0.05), ICU stay ((5.4 ± 2.1) d vs (8.0 ± 1.4) d, p < 0.05), hospital stay ((10.1 ± 3.0) d vs (15.3 ± 2.6) d, p < 0.05) between group A and B.ConclusionMidazolam sequential with dexmedetomidine can reach the goal of sedation for ICU agitated patients, meanwhile it can maintain the respiratory and circulation parameters and reduce adverse reactions.

Bone destruction and abnormal immunity always occur in patients with multiple myeloma (MM), which manifested by impaired osteoblasts and immune system. In this study, we investigated the quantity and function of osteoblasts by co-culture, the status of cellular immunity by flow cytometry, and the relationship between them in MM patients. The results showed that the numbers and function of osteoblasts in MM patients were lower than those in normal controls. Bortezomib could increase the numbers, calcium depositions and the expression of Bone morphogenetic protein–2 (BMP-2) mRNA of osteoblasts from MM patients in vitro. The status of cellular immunity in MM patients was abnormal, including decreased ratio of CD4+/CD8+, DC1/DC2 and Th1/Th2, and increased ratio of regulatory T cells. The ratio of CD4+/CD8+(r = 0.685) and CD4+CD25+/CD3+T(r = 0.568) were positively correlated with the quantity of osteoblasts (both P < 0.05). The serum interleukin-7(IL-7) level of MM patients was higher than that of normal controls (2.07 ± 0.71 vs. 1.62 ± 0.15 ng/L, P < 0.05), and was negatively correlated with the quantity of osteoblasts (r = -0.682, P < 0.01). Our data indicated that the proliferation and osteogenic potential of osteoblasts in MM patients were decreased which could be recovered by bortezomib in vitro. The down-regulation of cellular immunity was correlated with the quantity of osteoblasts.

Abstract. Thymoma is a type of benign or low-grade malignant tumor, occurring on the thymic epithelium. Patients with thymoma may also suffer from myasthenia gravis (MG), presenting MG-associated thymoma. T cell immunoglobulin and mucin domain-3 (Tim-3), a subtype of the Tim protein family, may be an important immune regulatory and pivotal molecule associated with tumor development. In order to understand the etiology and pathogenesis of MG-associated thymoma in the Han population of North China, the present study investigated the association between a polymorphism on the -574 locus in the promoter of Tim-3 and the risk of MG-associated thymoma in the Han Chinese population. In total, 116 patients with thymoma and MG were enrolled into the MG-associated thymoma group, while 124 patients with thymoma, but without MG, were enrolled into the non-MG-associated thymoma group. Examinations were conducted to reach a definite diagnosis of thymoma and MG and rule out other autoimmune diseases. Allele-specific polymerase chain reaction (AS-PCR) was performed to determine the polymorphism on the -574 locus of Tim-3 in all the subjects. PCR products were randomly selected for sequencing. Statistically significant differences were detected between the distribution frequencies of the GT+TT genotype and T allele on the -574 locus of the MG-associated thymoma group (31.03 vs. 12.90%, respectively; χ 2 =11.609, P=0.001) and the non-MG-associated thymoma group (15.52 vs. 6.45%, respectively; χ 2 =10.198, P=0.001). In conclusion, the present study indicated that an association may exist between the polymorphism of the -574 locus in the Tim-3 promoter and MG-associated thymoma. IntroductionThymoma is a type of benign or low-grade malignant tumor, developed on the thymic epithelium, and the most frequent anterior mediastinal neoplasm in adults; however, its overall incidence is only 0.13 per 100,000 individuals/year according to data from the Surveillance, Epidemiology and End Results database (1-3). Due to the low incidence of this neoplasm, its etiology and pathogenesis remain unknown. In addition, epidemiological data have revealed that 20-25% of patients with thymomas also suffer from myasthenia gravis (MG; hereafter referred to as MG-associated thymoma), whereas 10-20% of myasthenic patients suffer from thymomas (4). MG, is an autoimmune disease of unclear etiology, results in even more complex etiology and pathogenesis of MG-associated thymoma. The ratio of patients with thymoma and MG is higher than that of any ofther autoimmune disease. Pivotal markers and cross-linked molecules of thymoma and MG have been the aim of several previous studies (5,6).Thymus is a primary organ and the initial site for the development of the T cell immunological function (7). The development of thymoma is frequently accompanied by a rich infiltrate of T cells (3). When released into the circulation, these abnormally conditioned T cells are hypothesized to be responsible for the autoimmune conditions that often accompany thymoma, particularly MG (...