Progression on Multifunctional Nanoparticles Interfering with Cell Membrane Transporters-associated Drug Resistance / 中国医学科学院学报

Multi-drug resistance(MDR)refers to the loss of sensitivity of tumor cells to traditional chemotherapeutics agents under the mediation of various mechanisms,resulting in the reduction of chemotherapy efficacy.Current studies suggest that a variety of factors,including cell membrane transporter-mediated efflux of anti-tumor drugs,special microenvironment in tumor tissue,DNA self-repair and anti-apoptotic process,and epithelial-mesenchymal cell transformation,may contribute to the formation of MDR.Cell membrane transporter-mediated drug efflux refers to an increase in the amount of anti-tumor drug pumped out of the cell through the up-regulation of the ATP-binding cassette transporter on tumor cell membrane,which reduces the concentration of the drug in the cell,thus forming MDR.An effective method to inhibit the efflux pump caused by overexpression of membrane transporters plays an important role in overcoming MDR.As a promising drug delivery system,multifunctional nanoparticles have demonstrated many advantages in antitumor therapy.Meanwhile,nanoparticles with tailored design are capable of overcoming MDR when combined with a variety of strategies.This paper described in detail the studies relevant to the use of multifunctional nano-sized drug delivery system combined with different strategies,such as co-delivery of agents,external responsiveness or target modification for intervention with efflux pump in order to reverse MDR.This paper provides reference for the development of nano-sized drug delivery system and the formulation of reversal strategy in the future.

Influence of amlodipine combined valsartan on autonomic nervous function and Rho‐associated protein kinase1 in hypertensive patients with renal injury／ / 心血管康复医学杂志

Objective :To study influence of amlodipine combined valsartan on autonomic nervous function and serum level of Rho‐associated protein kinase 1 (ROCK1) in hypertensive patients with renal injury .Methods :A total of 94 hypertensive patients with renal injury treated in our hospital were selected ,randomly and equally divided into amlo‐dipine group and combined treatment group (received amlodipine combined valsartan ) ,both groups were treated for one month .Serum ROCK1 level and autonomic nervous function indexes before and after treatment ,therapeutic effect and incidence of adverse reactions were analyzed and compared between two groups .Results :After treat‐ment ,total effective rate of combined treatment group was significantly higher than that of amlodipine group (95. 74% vs.82.97%,P＝0. 045).Compared with before treatment ,after treatment ,there were significant reduc‐tions in serum ROCK1 level [amlodipine group : (3. 25 ± 0.32 ) ng／ml vs.(1.24 ± 0. 45 ) ng／ml ,combined treat‐ment group :(3. 34 ± 0. 35) ng／ml vs.(0.22 ± 0.15 ) ng／ml] ,24hSBP standard deviation (24hSSD) ,24h DBP SD (24hDSD) ,daytime SBP SD (dSSD) ,nighttime SBP SD (nSSD) and nDSD in two groups ( P＝0.001 all) ,and a‐bove indexes of combined treatment group were significantly lower than those of amlodipine group , P＜ 0. 01 all. Compared with amlodipine group after treatment ,there were significant reductions in incidence rates of lower limb edema (27. 66% vs.10.63%) ,nausea and vomiting (27. 66% vs.8.51%) and dizziness and weakness (23. 40% vs. 8.51%) in combined treatment group ,P＜0. 05 all.Conclusion :Amlodipine combined valsartan possesses significant therapeutic effect on hypertensive patients with renal injury .It can significantly reduce serum ROCK1 level and im‐prove autonomic nervous function and prognosis in these patients .

Therapeutic angiogenesis induced by hepatocyte growth factor directed by ultrasound-targeted microbubble destruction / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the feasibility of therapeutic angiogenesis in myocardial infarction induced by hepatocyte growth factor (HGF) mediated by ultrasound-targeted microbubble destruction.</p><p><b>METHODS</b>Forty Wistar rats were divided into 4 groups after the models of myocardial infarction were established: HGF + ultrasound + microbubble (HGF + US/MB) groups, HGF and ultrasound (HGF + US) group, HGF and microbubble (HGF + MB) group, and surgery alone (SA) group. Ultrasound-targeted destruction microbubble loaded with HGF gene with ECG trigger was performed in HGF + US group. Microbubble loaded with HGF gene was infused intravenously in HGF + MB group, and normal saline were infused in SA group. All rats were killed 14 days after transfection. The CD34 expression was detected by immunohistochemistry (IHC), and microvessel density (MVD) was counted in high power field. The HGF expression on myocardium was detected by ELISA, and the correlation between the contents of HGF and MVD in myocardium was analyzed.</p><p><b>RESULTS</b>IHC results showed that CD34 expressions, shown as brown granules, were located on the membrane and endochylema of vascular endothelial cells. The MVD in HGF + US/MB group [ (266.9 +/- 39.8) /HPF] were highest among all the groups. The contents of HGF in myocardium were highest in HGF + US/MB group [(5.54 +/- 0.81) ng/g], and the contents of HGF in anterior wall were significantly higher than those in posterior wall (P < 0.05); the difference was also significant when compared with others groups (P < 0.01). The correlation analysis showed the contents of HGF was positively correlated with MVD in myocardium.</p><p><b>CONCLUSION</b>Ultrasound-targeted microbubble destruction can effectively deliver HGF into the infracted myocardium and facilitate angiogenesis, which provides a novel way in the gene therapy of myocardial infarction.</p>