BACKGROUND:Related studies have showed that poly D,L-lactide-co-glycolide can effectively package antisense oligonucleotides, smal interfering RNA, microRNA. Poly D,L-lactide-co-glycolide can better protect them against the destruction of the enzymes in vivo and have slow the drug release. Therefore, the number of drug administration can be reduced to achieve a long-term and effective therapeutic effect. ＜br> OBJECTIVE:To prepare poly D,L-lactide-co-glycolide-CXCR4-miRNA-nano-particles and to research the characteristics of the prepared nanoparticles. ＜br> METHODS:Poly D,L-lactide-co-glycolide-CXCR4-miRNA nanoparticles were prepared by double emulsion-evaporation process. Ultraviolet spectrophotometry was utilized for measurement of encapsulation efficiency and drug-loading rate, observing the shape of nanoparticles by transmission electron microscope, and measuring the size and distribution of nanoparticles by laser particle size analyzer. Sustained-release characteristics of nanoparticle suspension were observed in phosphate buffer. ＜br> RESULTS AND CONCLUSION:The prepared nanoparticles were spherical-shaped, smooth, evently distributed and inadhesive. The particle size was mainly distributed within 143-502 nm, with an average diameter of 280 nm. The average drug loading was (0.515±0.023)%, the average encapsulation ratio was 50.2%and difference between batches was smal . The nanoparticles could slowly release in vitro and the process initial y experienced the fast-release stage, and then reached a basical y stable platform stage at day 14. These finding indicate that the process to prepare poly D,L-lactide-co-glycolide CXCR4-miRNA-nanoparticles by double emulsion-evaporation is simple. The prepared nanoparticles are wel targeted and exhibit sustained-release effects.

Animal models of pulmonary artery hypertension (PAH),aiming to simulate human characteristics of the disease,have contributed extensively to understanding the pathophysiology of PAH and the investigation of experimental treatments.The classical models include monocrotaline models,chronic hypoxia model and so on,more new models were investigated in recent years.These animal models were not able to perfectly mimic human pathological characteristics of PAH because of the defect in different aspects.In this review,both typical and novel methods of PAH modeling were summarized and evaluated to provide a suitable guidance for the settlement of animal models which can meet human characteristics comprehensively.

65 years old) with in-stent restenosis were randomly divided into two groups: cutting balloon(38 cases) and conventional balloon angioplasty(31 cases) group. Quantitative coronary angiography(QCA) and intravascular ultrasound(IVUS) were underwent before and immediately after the balloon inflation. Within 6-months clinical and angiographic follow-up, clinical improvements and QCA results were recorded. himary end points included myocardial infarction, coronary artery bypass graft(CABG) and revascularization. Results The procedural success rate was 100% in both groups. One patient in cutting balloon experienced dissection in the site distal to stent. Average follow-up time was (6.7?0.3) months. The angiographic stenosis rates at the 3- and 6-month in cutting balloon group were markedly lower than that in conventional balloon group(15% and 38% vs 18% and 43%, respectivelly, P

Objective To access the expression and clinical significance of CD19+CD5+B cells and interleukin (IL)-10 in patients with systemic lupus erythematosus (SLE). Methods Forty-six SLE patients and ten healthy controls were recruited in the Second Affiliated Hospital of Shanxi Medical University. CD19+CD5+B cells subsets were detected with flow cytometry. IL-10 level in serum were detected with enzyme linked immunosorbent assay (ELISA). The correlation between the expression of CD19+CD5+B cells and serum level of IL-10 with ESR, systemic lupus erythematosus disease activity index (SLEDAI) score and complement was analyzed. Pair-wise comparison of means of groups was conducted with one-way ANOVA. Comparison between the two groups was conducted by LSD-t test. Correlations between variables were carried out using Spearman's rank correlation test. Results The percentage of CD19+CD5+B cells in peripheral blood of SLE patients [(5.7±2.1)%] was significantly lower than those in healthy control group [(19.1±2.9)%](t=2.431, P=0.005), and it had a negative correlation with SLEDAI score (r=-0.292, P=0.049). The IL-10 serum level of SLE patients [(18.8±13.5) pg/ml] was significantly higher than the healthy control group [(8.3±2.9) pg/ml] (t=3.021, P=0.003), and it had a positive correlation with SLEDAI score (r=0.322, P=0.029). Conclusion CD19+CD5+B cells and IL-10 may participate in the occurrence and development of SLE. The changes of CD19+CD5+B cells and IL-10 in the peripheral blood might contribute to the pathogenesis and correlate with the disease activity of SLE.

Objective To measure the number of lymphocytes, B lymphocytes, CD5+B lymphocytes and level of IL-10 in peripheral blood of patients with systemic lupus erythematosus (SLE), and analyze their effects in the disease. Methods In this study, 84 cases of patients with SLE were randomly selected and evaluated according to the activity index (SLEDAI). These cases were divided into low activity group (SLEDAI<9) and high activity group (SLEDAI≥9). Ten healthy individuals were selected as the control group at the same time. The number of peripheral blood lymphocytes, B lymphocytes, CD5 + B lymphocytes, erythrocyte sedimentation rate (ESR), C3, C4 and interleukin (IL)-10 levels in serum were measured respectively and the correlation between the above indexes and SLEDAI and complement levels were analyzed. Pair-wise comparison of means of groups was conducted with one-way ANOVA. Comparison between the two groups was conducted by LSD-t test. Correlations between variables were carried out using Spearman's rank correlation test. Results The total number of lymphocytes in SLE group was lower than that in normal control group ( F=7.216, P<0.001); The number of CD19+ B lymphocytes in SLE group was higher than that in normal control group (F=3.589, P=0.036). The number of CD5+B lymphocytes of peripheral blood [(2.5±0.6)%] in patients with systemic lupus erythematosus was significantly lower than that in the normal control group [(3.2 ±0.8)%], but the difference was not statistically significant (t=3.412, P=0.698). The number of CD5+B lymphocytes in the high activity group was significantly lower than that in the low activity group (t=7.365, P=0.027)and the normal control group (t=5.649, P=0.002). The number of CD5+ B lymphocytes was negatively correlated with SLEDAI score (r=-0.692, P=0.001) and positively associated with the level of complement 3 (r=0.305, P=0.038), but not with complement 4 and ESR (P>0.05). In addition, the level of serum IL-10 in whether the low activity group (t=1.935, P=0.031) or the high activity group (t=3.048, P=0.012) was all higher than the normal control group. The level of serum IL-10 in patients with systemic lupus erythematosus was positively associated with SLEDAI score (r=0.425, P=0.024) and ESR (r=0.479, P=0.008), but was negatively correlated with complement 4 (r=-0.359, P=0.031). Conclusion The total number of lymphocytes in patients with SLE decreases significantly, while B lymphocytes increases significantly. The number of CD5+ B lymphocytes and the serum IL-10 level are also changed. It maybe related to the patient's inflammatory environment, and the number of CD5+B lymphocytes and the serum IL-10 level may be associated with disease activity.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.