Engineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor.

Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1α (HIF-1α) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.

Percutaneous reduction and intramedullary fixation technique for displaced pediatric radial neck fractures.

This study investigated the outcome of displaced pediatric radial neck fractures treated by percutaneous leverage reduction and intramedullary fixation using Kirschner wires. Twenty-three patients with displaced radial neck fractures were treated following this technique. Adequate reduction was achieved in each patient. Twenty-one patients were followed up for 37 months on average. All fractures healed. Malunion occurred in three patients with an average residual angulation of 7.3°. According to the MEPI, excellent outcome was achieved in 15 patients and good outcome in six. Therefore, this technique is an effective alternative for the treatment of pediatric radial neck fractures.

[The effects of the autologous venous external stents on intimal hyperplasia of the vein grafts in rabbits].

OBJECTIVE: To assess the effect of the autologous venous external stents on intimal hyperplasia of the vein grafts in rabbits. METHODS: Thirty-six male New Zealand white rabbits, aged 5 months and weighing 2.8 to 3.0 kg, were randomly divided into 3 groups: group A, group B and group C, with 12 rabbits in each group. First, a section about 6 cm long of vein was cut from the right external jugular vein of each rabbit and severed to have 3 equal-length segments. Next, each distal segment prepared for anastomosis. The proximal segment invaginating middle segment in group A and only middle segment in group B were used for the external stent. Later, the left common carotid artery was separated from surrounding tissue, from it a section about 0.5 cm long was cut away. Finally, the vein graft was inverted and end-to-end anastomosed to the two ends of the artery with a 9-0 suture. After bloodstream re-established, the diameter of each vein graft was measured. At 2 and 4 weeks postoperative, the graft veins were cut off and histologically examined by the means of HE staining and Masson staining. The smooth muscle cells (SMC) proliferation was studied by the immunohistochemical detection of proliferating cell nuclear antigen. RESULTS: After bloodstream re-established, the diameters of vein graft of group A and group B and group C were (1.6 +/- 0.3) mm, (2.2 +/- 0.4) mm and (2.6 +/- 0.6) mm respectively (P < 0.05). At 4 weeks postoperative, the data of the ratio of intima to media thickness and the index of the proliferating cells of the intima were as follow: group A (1.01 +/- 0.07 and 6.84 +/- 1.98), group B (1.32 +/- 0.08 and 11.01 +/- 2.61), group C (1.55 +/- 0.03 and 14.96 +/- 4.14). Both the data of group A were obviously less than that in group B, and that of group B was less than group C (P < 0.05). CONCLUSION: The autologous venous two-layer external stents inhibit intimal hyperplasia of the vein grafts.

[Experimental study on rho-kinase inhibitor by intravenous injection inhibiting intimal hyperplasia in vein grafts].

OBJECTIVE: To investigate the effects of Rho-kinase inhibitor--fasudil hydrochloride hydrate on vein graft intimal hyperplasia in vivo. METHODS: Twenty-four healthy rabbits (2.3-2.5 kg) were randomly divided into two groups (n=12). Fasudil hydrochloride hydrate (experimental group) and normal sodium (control group) were given 3 days before operation with 30 mg/kg by intravenous injection everyday and continued until the end of the experiment. After a longitudinal incision, the femoral vein and the femoral artery were exposed about 3 cm. An approximately 2.5 cm segment of the famoral vein was harvested for the reversed-vein graft. The femoral artery was removed 1 cm segment and replaced by the harvested femoral vein. At 2 and 4 weeks after operation, the grafts were stained with HE to observe the thickness of the intima. Furthermore, the proliferating cell nuclear antigen (PCNA) and transmission electron microscope was used to study the proliferation of smooth muscle cell. In situ apoptosis was detected by TUNEL assay. RESULTS: All rabbits survived till the end of the experiment. The color Doppler imaging examination showed that all grafts were patency. At 2 and 4 weeks after the operation, HE staining showed that the intimal hyperplasia were obvious in the two groups. There were lots of cells in the intima, and more fusiform smooth muscle cells in the media. At 2 and 4 weeks, the intimal thickness were (30.33 +/- 3.23) microm and (43.11 +/- 4.92) microm in experimental group and were (44.83 +/- 3.53) microm and (66.16 +/- 8.45) microm in control group. The rates of PCNA positive cell were 14.28% +/- 2.76% and 7.61% +/- 1.06% in experimental group and were 20.08% +/- 3.56% and 8.73% +/- 1.35% in control group. The rates of TUNEL positive cell were 3.55% +/- 0.36% and 1.22% +/- 0.18% in experimental group and were 1.11% +/- 0.31% and 0.55% +/- 0.11% in control group. There were significant differences (P < 0.05) between the two groups at 2 weeks or 4 weeks, between 2 weeks and 4 weeks within group. CONCLUSION: Intravenous injection of fasudil hydrochloride hydrate is an effective method for prevention of vein graft intimal hyperplasia of rabbit.

[Quantitative evaluation of postoperative effect of calcaneal fractures using Footscan system].

OBJECTIVE: To investigate the value of using Footscan system to evaluate the therapeutic effect of two internal fixation methods on calcaneus fractures. METHODS: From February 2006 to September 2006, 64 patients with fresh unilateral closed calcaneus fractures were randomly divided into two groups. The experimental group: 32 patients underwent minimally invasive open reduction and internal fixation with improved compressing plate and screw, including 28 males and 4 females aged 20-53 years old (average 36.7 years old); the course of disease was 3-14 days; there were 19 cases of type II, 11 of type III, and 2 of type IV according to Sanders fracture classification system. The control group: 32 patients underwent internal fixation of standard AO plate via L-shaped incision, including 29 males and 3 females aged 18-56 years old (average 37.1 years old); the course of disease was 4-15 days; there were 18 cases of type II, 11 of type III and 23 of type IV according to Sanders fracture classification system. No significant difference was noted between two groups in the general information (P > 0.05). At 1 and 2 years after operation, dynamic plantar pressure was measured using Footscan system, Maryland foot scores of two groups was compared, and statistical analysis was performed. RESULTS: All patients were followed up for 2 years. No infection, cuticular border necrosis, and sural nerve distal end injury occurred in the experimental group, whereas in the control group, 3 patients suffered from cuticular border necrosis and recovered after dressing, and 1 patient had sural nerve distal end injury with decreased sensation in local skin. At 1 and 2 years after operation, in the control group, there were significant differences between the injured foot and the normal foot in terms of impulse, instep index, motion range of subtalar joint, lateral displacement of footplate pressure center, and calcaneal width when patients stood on both feet (P < 0.05), whereas in the experimental group, no significant differences were noted between the injured foot and the normal foot in terms of the above parameters (P > 0.05). Significant differences were noted between two groups in terms of the above parameters (P < 0.05). The Maryland score 1 year after operation was (86.74 +/- 8.56) points for the experimental group and (71.24 +/- 10.06) points for the control group; at 2 years after operation, it was increased to (87.35 +/- 8.49) points and (72.41 +/- 9.69) points, respectively, indicating there was a significant difference between two groups (P < 0.05). CONCLUSION: Operative outcomes of internal fixation with improved compressing plate are superior to those of standard AO plate. Footscan system can provide a quantitative assessment on the operative effect of calcaneus fractures.

[Inhibitory effect of topical application of 5-fluorouracil on intimal hyperplasia of vein graft].

OBJECTIVE: To assess the effect of topical application of 5-fluorouracil (5-FU) on intimal hyperplasia in rabbit vein graft. METHODS: Sixty-four male New Zealand white rabbits, aged 5 months and weighing 2.8-3.0 kg, were randomly divided into group A, B, C, and D (n = 16 rabbits per group). Artery defect model was established by cutting about 1 cm artery from the middle part of the dissociated left common carotid artery. A section about 3 cm was cut from the right external jugular vein, and the harvested vein was inverted and end-to-end anastomosed to the artery defect with 9-0 non-traumatic suture. After anastomosis, the extima of the grafted veins in group A, B, and C was completely wrapped with cotton sheet (12 mm x 30 mm x 1 mm in size) immersed by 5-FU at a concentration of 50.0, 25.0, and 12.5 mg/mL, respectively, and each vein was treated 5 times (1 minute at a time). In group D, the extima of the graft veins was treated with normal saline instead of 5-FU. The grafted veins were obtained 1, 2, 4, and 6 weeks after operation, HE staining and Masson staining were preformed for histological changes of grafted vein wall, proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and TUNEL labeling staining were conducted for proliferation and apoptosis of smooth muscle cell of the grafted vein, and transmission electron microscope observation was performed for cellular ultrastructure. RESULTS: The HE staining, Masson staining, and PCNA immunohistochemistry staining showed that the thickness of intima in group A and B was obviously less than that in group C and D at 1, 2, 4, and 6 weeks after operation, and the proliferation cells in group A and B were less than that in group C and D at 1, 2, and 4 weeks after operation. The thickness of the intima, the degree of intima hyperplasia, the degree of vessel lumen stenosis of four groups at different time points were as follows: at 1 week after operation, group A [(12.69 +/- 1.68) microm, 0.73 +/- 0.05, 0.025 +/- 0.003], group B [(17.52 +/- 2.01) microm, 0.86 +/- 0.06, 0.027 +/- 0.004], group C [(21.92 +/- 1.85) microm, 1.06 +/- 0.09, 0.036 +/- 0.006] and group D [(26.45 +/- 3.86) microm, 1.18 +/- 0.08, 0.041 +/- 0.005]; at 2 weeks after operation, group A [(24.61 +/- 2.91) microm, 0.86 +/- 0.06, 0.047 +/- 0.003], group B [(37.28 +/- 2.78) microm, 1.17 +/- 0.09, 0.060 +/- 0.004], group C [(46.52 +/- 2.25) microm, 1.44 +/- 0.08, 0.073 +/- 0.003], and group D [(52.07 +/- 3.29) microm, 1.45 +/- 0.05, 0.081 +/- 0.006]; at 4 weeks after operation, group A [(61.09 +/- 6.84) microm, 1.38 +/- 0.08, 0.106 +/- 0.007], group B [(63.61 +/- 8.25) microm, 1.40 +/- 0.07, 0.107 +/- 0.010], group C [(80.04 +/- 7.65) microm, 1.64 +/- 0.07, 0.129 +/- 0.011], and group D [(84.45 +/- 9.39) microm, 1.68 +/- 0.10, 0.139 +/- 0.014]; at 6 weeks after operation, group A [(65.27 +/- 5.25) microm, 1.46 +/- 0.07, 0.113 +/- 0.005], group B [(65.82 +/- 7.12) microm, 1.45 +/- 0.05, 0.112 +/- 0.011], group C [(84.45 +/- 9.39) microm, 1.69 +/- 0.09, 0.135 +/- 0.007], and group D [(87.27 +/- 8.96) microm, 1.76 +/- 0.05, 0.140 +/- 0.012]. Group A and B were inferior to group C and D in terms of the above three parameters and cell proliferation index 1, 2 and 4 weeks after operation (P < 0.05). Group A and B were superior to group C and D in terms of cell apoptosis index of intima and media 1 and 2 weeks after operation (P < 0.05). Transmission electron microscope observation showed that the synthetic cell organelles such as rough endoplasmic reticulum, golgi apparatus, and ribosome in group A and B were obviously less than those in group C and D (P < 0.05). CONCLUSION: Topical application of 5-FU can effectively inhibit intima hyperplasia of the vein grafts.

[Clinical observation on the different treatments targeted at different types of radial head fracture and radial neck fracture].

OBJECTIVE: To assess the effect of the different treatments targeted at different types of radial head fracture and radial neck fracture. METHODS: A retrospective study was performed in 87 patients from February 2006 to March 2007. Fifty-four patients with radial head fractures included 36 males and 18 females, aged from 18 to 65 years (the average age was 33); Forty of them resulted from crashing, 8 from traffic injury and 6 from falling injury. According to Mason classification system, there were 15 type I, 23 type II and 16 type III. Thirty-three patients with radial neck fractures included 21 males and 12 females, aged from 9 to 17 years (the average age was 13), 29 of them resulted from crashing, 1 from traffic injury and 3 from falling injury. According to O'Brien classification system, there were 8 type I, 14 type II and 11 type III. Type I of radial head fractures and radial neck fractures were immobilization with cast, the patients with type II of radial head fractures were treated with open reduction and micro-screw or T-trapezoid and bridge-shaped plate fixation and type III had operations to fix with bridge-shaped locked plate and repair the broken annular ligament, or replace heads with prosthesis. All patients with type II and type III of radial neck fractures were treated with closed reduction by leverage and percutaneous intra-medullary nailing. RESULTS: The patients were followed up for 4-12 months (mean 7.2 months). The functional recovery degrees were evaluated with Wheeler's evaluation system. In group of radial head fractures, the results were excellent in 26 patients, good in 20, fair in 6 and poor in 2, the excellent and good rate was 85.2%. In group of radial neck fractures, the results were excellent in 20 patients, good in 9, fair in 4 and poor in no patient, and the excellent and good rate was 87.9%. CONCLUSIONS: Different types of fractures should choose different surgical methods according to their characters. The excellent functional recovery depend on anatomical reduction, retaining the head of radius, early repairing and protecting the broken annular ligament of radius, and early functional training.

[Effects of 5-fluorouracil on tendon adhesion formation after flexor tendon repair].

OBJECTIVE: To evaluate the effect of 5-fluorouracil (5-FU) applied topically on preventing adhesion and promoting functional recovery after tendon repair. METHODS: From August 2003 to June 2007, 48 patients with flexor tendon rupture of the fingers by sharp instrument were treated and randomly divided into two groups. In 5-FU group, 39 fingers of 26 patients included 17 males and 9 females, aged (29.3 +/- 9.8) years; the locations were zone I in 19 fingers and zone II in 20 fingers; single finger was involved in 12 cases and more than 2 fingers were involved in 14 cases; and the time from injury to operation was (2.4 +/- 1.6) hours. In control group, 36 fingers of 22 patients included 14 males and 8 females; aged (26.1 +/- 8.7) years; the locations were zone I in 16 fingers and zone II in 20 fingers; single finger was involved in 10 cases and more than 2 fingers were involved in 12 cases; and the time from injury to operation was (2.1 +/- 1.8) hours. No statistically significant difference was found in constituent ratio of age, gender, injured fingers and their zones, between two groups (P > 0.05). The repair site in 5-FU group was given 5-FU at a concentration of 25 mg/mL with a soaked sponge, and the synovial sheath of the repaired site was wrapped with the 5-FU-soaked sponge for 1 minute for 4 times after the tendons were repaired; normal saline was used in the control group. RESULTS: Wound healed by first intention and no infection and tendon rupture occurred in two groups. The patients were followed up for 3-8 months (mean 4.1 months) and 3-8 months (mean 3.9 months) in 5-FU group and in control group respectively. The functional recovery degrees of the fingers were evaluated with total active movement (TAM) evaluation system. In 5-FU group, the results were excellent in 22 fingers, good in 13 fingers, fair in 3 fingers and poor in 1 finger; the excellent and good rate was 89.7%. In control group, the results were excellent in 11 fingers, good in 15 fingers, fair in 9 fingers and poor in 1 finger; the excellent and good rate was 72.2%. There was statistically significant difference in the functional recovery degrees of fingers between two groups (P < 0.05). The 2 fingers which had a poor result in 5-FU group and control group were served with tenolysis was performed in 2 cases having poor results after 6 months of operation and had an excellent result at last. CONCLUSION: 5-FU applied topically can reduce tendon adhesions after the ruptured tendon repair.

[An effect of 5-fluorouracil on tendon adhesion formation after flexor tendon repair in chickens].

OBJECTIVE: To assess an effect of 5-fluorouracil (5-FU) applied topically on the tendon adhesion and the healing process after the flexor tendon repair in Leghorn chickens. METHODS: Thirty-two white Leghorn chickens, aged 4 months and weighing 1.5-1.7 kg, were randomly divided into 2 groups: Group A and Group B, with 16 chickens in each group. The flexor digitorum profundus tendons of the 2nd, 3rd and 4th toes were transected and repaired. The repair site in Group A was given 5-FU in a concentration of 25 mg/ml with a soaked sponge that was cut into pieces 7 mm X 20 mm x 1 mm in size, and the synovial sheath of the repair site was wrapped with the 5-FU-soaked sponge for 1 min for 4 times. The repair site in Group B was served as a control, with no 5-FU but with the sterile normal saline. At 3 and 6 weeks postoperatively, the repaired tendons and the tendon adhesion formation were examined macroscopically and histologically, and the repaired tendons were tested biomechanically. The tissue blocks from the tendon repair site were examined under the transmission electron microscope. RESULTS: At 3 and 6 weeks postoperatively, the macroscopic and histological observation showed that the peritendinous adhesions in Group A were looser when compared with those in Group B. The length of the tendon gliding and the extent of yieldance to exercise were found to be 4.85+/-1.31 mm, 0.67+/-0.42 mm and 5.74+/-1.61 mm, 1.55+/-0.35 mm respectively at 3 and 6 weeks after operation in Group A,but 2. 99+/-0.51 mm,0.24+/-0.14 mm and 3.65+/-0.54 mm, 1.22+/-0.16 mm in Group B. Group A was significantly greater in the above-mentioned parameters than Group B (P<0.05). At 3 weeks after operation, the ultimate breaking strength was 20.28 +/- 4.92 N in Group A and 21.29 +/- 4.88 N in Group B, with no statistically significant difference found between the two groups (P>0.05). At 6 weeks, the ultimate breaking strength was 47.12+/-6.76 N in Group A but 39. 31 +/- 7.20 N in Group B, with a significant difference between the two groups (P < 0.05). CONCLUSION: 5-fuorouracil, when applied topically, can reduce the tendon adhesion, with no inhibition of the intrinsic healing mechanism. It is an ideal treatment strategy to prevent peritendinous adhesion.