Artificial tumor microenvironment regulated by first hemorrhage for enhanced tumor targeting and then occlusion for synergistic bioactivation of hypoxia-sensitive platesomes

The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely "platesomes", which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.

The reproducibility of anterior, middle and posterior diaphragm motion assessments with ultrasound / 中华物理医学与康复杂志

Objective:To explore the reproducibility of ultrasound measurements of children′s anterior, middle and posterior diaphragm motions.Methods:Thirty children admitted to a pediatric intensive care unit were positioned supine and a 5MHz ultrasound probe was placed over the intersection of their right midclavicular line with the costal margin. M-mode ultrasound was used to record the excursion and contraction velocity of the anterior, middle and posterior diaphragm during respiration. The observations were duplicated so the repeatability of the measurements could be evaluated using intra-group correlation coefficients calculated for the diaphragm excursions and the contraction velocities. Analysis of variance was used to explore the differences in excursion and contraction velocity among different parts of the diaphragm.Results:The intra-group correlation coefficients calculated for the anterior, middle and posterior diaphragm were 0.89, 0.95 and 0.90 respectively. The corresponding values for the contraction velocities were 0.90, 0.94 and 0.95 respectively. Both variables measured by ultrasound showed high repeatability. The average anterior, middle and posterior diaphragm excursion values (in mm) were 8.1±3.1, 7.4±3.0 and 5.5±2.3, and the corresponding average contraction velocities (in mm/s) were 12.5±4.8, 11.5±6.3 and 8.9±4.0.Conclusions:Measurements of children′s diaphragm motions using ultrasound show high repeatability. The excursions and contraction velocities of the anterior, middle and posterior diaphragm differ in children. The motion of one part of the diaphragm cannot represent the functioning of the entire diaphragm.

The effects of extracorporeal shock wave treatment combined with expanding bone marrow autografts in the treatment of nonunion of femoral shaft fractures with interlocking intramedullary nails / 中华物理医学与康复杂志

Objective To investigate the effect of extracorporeal shock waves (ESWs) combined with expanding bone marrow autografts in treating nonunion of femoral shaft fractures with interlocking intramedullary nails.Methods Thirty patients with femoral shaft fractures which had not united were divided into an ESW group,an expanding bone marrow group,and a combined treatment group using a table of random numbers.Each group had 10 cases.In the ESW group,no expanding bone marrow was employed in fixing the intramedullary nails and ESW therapy was begun at day 14 after the operation.In the expanding bone marrow group,bone marrow was grafted around the broken ends of fractured bones.In the combined treatment group patients underwent both treatments.The conditions of the callus and the fracture lines in the 3 groups were separately evaluated using X-rays at the 4th,8th,12th and 16th week after the operation.Results At week 4,the average callus and fracture line scores in the combined treatment and expanding bone marrow groups were significantly better than those in the ESW group.At the 8th week after the operation,the average callus and fracture line scores in the combined treatment group were significantly higher than in the ESW group and expanding bone marrow groups.Later,the callus and fracture scores in all 3 groups continued to rise significantly.At the 12th and 16th week the scores in the combined treatment group were significantly better than those in the ESW group and the expanding bone marrow group,while the scores in the ESW group were significantly better than those in the expanding bone marrow group.The cure rates in the ESW,bone marrow and combined treatment groups were 60％,50％ and 100％ respectively at week 16.Conclusions The combined treatment was significantly more effective than either treatment alone.There was no significant difference in effectiveness between the ESW and expanding bone marrow treatments.ESW combined with expanding bone marrow autograft is an effective way to promote bone knitting in the treatment of nonunion of femoral shaft fractures with interlocking intramedullary nails.

Study on pharmacokinetics of HCPT nanosuspensions with ability of inhibiting P-gp in rats after oral administration / 中国中药杂志

<p><b>OBJECTIVE</b>To study on pharmacokinetics of hydroxycamptothecine (HCPT) nanosuspensions in rats after oral administration.</p><p><b>METHOD</b>The plasma concentrations of HCPT were determined by HPLC-FD. The analysis was performed on a diamonsil C18 column (4.6 mm x 200 mm, 5 microm) with 0.3% acetic acid-triethylamine buffer (pH 5.0) and methanol (57: 43) as mobile phase. The flow rate was 1.0 mL x min(-1); the excitation wave was set at 363 nm, and emission wave was set at 550 nm; the temperature was 35 degrees C. All data of concentration-time of HCPT were treated with pharmacokinetics program DAS 2.0.</p><p><b>RESULT</b>The concentration-peak area of this assay had a good linear relation in the range from 1 to 50 microg x L(-1), and the minimum limit of quantitation was 1 microg x L(-1). The inter- and intra-day precisions of HCPT were smaller than 4.3%, and the accuracy were between -5.59% and 5.59%. The recoveries of HCPT in three plasma concentrations including high, medial, low concentration were 98.94%, 95.88% and 102.69%, respectively, which was in line with the request of biopharmaceutical analysis. The plasma concentration time profiles of HCPT fitted in two-compartment models well, and the main pharmacokinetic parameters found for HCPT after oral administration were as follows: Cmax 13.10 microg x L(-1), Tmax 0.75 h, t(1/2alpha) 8.242 h, t(1/2beta) 136.122 h, AUC(0-t) 116.77 microg x h x L(-1), AUC(0-infinity) 161.93 microg x h x L(-1).</p><p><b>CONCLUSION</b>The HPLC-FD method was simple, with good specificity, reproducibility, and could be used to investigate the pharmacokinetics and determinate the concentration of hydroxycamptothecin. The nanosuspension in this study could accelerate the oral absorption rate of HCPT, and make improving bioavailability of HCPT possible.</p>

Double-bundle posterior cruciate ligament reconstruction using bone-semitendinosns and gracilis tendons under arthroscope / 中国医师进修杂志

Objective To evaluate the method and effect of double-bundle posterior cruciate ligament (PCL) reconstruction using bone-semitendinosus and gracilis tendons under arthroscope.Methods The data of 16 patients was reviewed,who had underwent arthroscopic PCL reconstruction using the bone-semitendinosus and gracilis tendons from March 2004 to March 2007.A special technique using trephine was allowed for the cylindrical bone plugs attached to the semitendinosus and gracilis tendons.The femoral double-tunnel and the tibial tunnel were prepared,and the adequate press-fit fixations of tendon grafts were ensured within them.Results All patients were followed up.Before operation,the mean Lysholm score was 57 points (43-65 points).While 12 months later after operation,the mean Lysholm score was 86 points (68-92 points).The excellent and good results were obtained in 87.5%.Conclusions Arthroscopic PCL reconstruction using bone-semitendinosns and gracilis tendons can effectively improve the stability of the knee joint.The key to achieve a good treatment is that precise positions of femoral and tibial tunnels in operation and systematic rehabilitation trainings after operation were performed.

Effect of vascular endothelial growth factor on vascular regeneration of reconstructed posterior cruciate ligament allograft transplantation in rabbits / 中国组织工程研究

BACKGROUND: Currently,the research of posterior cruciate ligament (PCL) construction mainly focuses on the surgical technique or graft selection. However,studies on vascular regeneration after construction are few,especially those on allograft construction. OBJECTIVE: To observe the effect of vascular endothelial growth factor (VEGF) on vascular regeneration of reconstructed PCL with femur-anterior cruciate ligament (ACL)-tibia allograft in rabbits. DESIGN,TIME AND SETTING: The factorial design experiment was performed at the Orthopedics Laboratory of the Third Affiliated Hospital of Weifang Medical College from March 2006 to September 2007. MATERIALS: Sixty-eight adult female Japanese white rabbits,weighing (3.3?0.1) kg,were adopted. Twenty-three of them were used to excide the femur-ACL-tibia complexes to establish the animal model of PCL reconstruction with allograft. METHODS: Forty-five rabbits were randomly divided into 3 groups,15 rabbits in each group. In the control group,no additional treatments were applied. In the phosphate-buffered saline (PBS) group,0.2 mL of PBS was injected into the knee joint. In the VEGF group,30 ?g VEGF mixed with 0.2 mL PBS was injected into the knee joint. MAIN OUTCOME MEASURES: The immunological rejection of allograft was observed after reconstruction. Five rabbits were randomly selected in each group at 3,6,12 weeks,respectively,for immunohistochemistry staining; and the microvessel density of the medio-one-third ligament part of allograft was evaluated with the Chalkley scoring method. RESULTS: Forty-five rabbits were involved in the result analysis. There were no hydrops articuli or aneretic cartilage when every rabbit’s knee joint was opened. The gross morphology of the grafts was similar to normal posterior cruciate ligament. Immunological rejection,such as degeneration,necrosis,dilapsus or defluxion was not appeared. Plenty of good vascular tissue in the arthrosis could be seen in the VEGF group,but could not be found in the control group or in the PBS group. The microvessel density score of the allograft in the VEGF group was higher than that in the control group and PBS group (P