Self-assembled nanoparticles of reduction-sensitive poly (lactic-co-glycolic acid)-conjugated chondroitin sulfate A for doxorubicin delivery: preparation, characterization and evaluation.

In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5 µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96 h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20 mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96 h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825 µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.

Research progress of environment-responsive delivery system in the application of co-delivery gene and drug / 药学学报

With the development of polymeric materials and nanotechnology, the potential application of nanoscaled drug delivery system (NDDS) is gradually manifested in the field of pharmaceutics. Especially, NDDS has the obvious advantages in the delivery of gene or drug. Comparing to the delivery system of single-drug, co-delivery system of gene and drug can significantly improve the therapeutic effects by enhancing transfection efficiency of gene and reversing multidrug resistance, etc. The co-delivery systems of gene and drug, which had the triggered release characteristics in the inner and outer of tumor, could be constructed by introducing the environment-responsive (pH-responsive, redox-responsive and light-responsive, etc) groups into the co-delivery system. The antitumor activity was further improved. In the present paper, the environment- responsive delivery systems in the application of co-delivery gene and drug in recent years were reviewed, and their remarkable properties in the antitumor activity were analyzed and summarized.

Analysis of treatment effect of urinary kallidinogenase combined with edaravone on massive cerebral infarction.

The aim of the study was to investigate the clinical effect of urinary kallidinogenase combined with edaravone in the treatment of massive cerebral infarction. A total of 58 patients with massive cerebral infarction were admitted to hospital between January 2013 and January 2014. There were 34 male and 24 female patients. The patients were randomly divided into the observation and control groups (n=29 cases per group). The patients in the control group received edaravone treatment, while patients in the observation group were treated with urinary kallidinogenase and edaravone. The clinical effects of the two groups were then compared. The results showed that the National Institutes of Health Stroke Scale score and serum C-reactive protein level of the patients in the two groups were significantly decreased following treatment. The decreased degree in the observation group was significantly smaller than that in the control group. The difference was statistically significant [(11.03±3.75) vs. (16.58±7.43) scores, P<0.05; (9.88±4.82) vs. (11.98±4.69) mmol/l, P<0.05]. The serum levels of vascular endothelial growth factor were significantly increased in patients of the two groups after treatment. The increased degree in the observation group was significantly higher than that in the control group. The difference was statistically significant [(268.51±77.34) vs. (188.82±57.33) ng/l, P<0.05]. The total effective rate of the observation group was significantly higher than that of the control group and the difference was statistically significant (89.66 vs. 62.07%, P<0.05). In conclusion, urinary kallidinogenase combined with edaravone treatment has a certain clinical curative effect on massive cerebral infarction.

A Meta-analysis of effect of biofeedback electrical stimulation therapy combined with pelvic floor ;muscle functional exercise on female stress urinary incontinence in China / 中国实用护理杂志

Objective To assess systematically the effect of biofeedback electrical stimulation therapy combined with pelvic floor muscle functional exercise on female stress urinary incontinence in China. Methods Relative literatures were searched by computer at home according to the inclusion and the exclusion criteria,which were analyzed by RevMan5.2 software, and literature selection and repetition were used according to the Note Express software. Results A total of 10 studies of randomized controlled or not randomized controlled trial were brought into the study by fixed effects model. A total of 969 cases were selected into the study, 496 in experimental group and 473 in control group. The results showed that biological feedback electrical stimulation therapy combined with pelvic floor muscle functional exercise could significantly improve the situation of female stress urinary incontinence ( OR=7.70, 95%CI 5.07-11.70, P<0.01). Removing the large sample literature, the results of sensitivity analysis were similar (OR=8.51, 95%CI 5.43-13.34, P<0.01), which indicated that the results were stable and reliable. Conclusions Biofeedback electrical stimulation therapy combined with pelvic floor muscle function exercise is a safe and effective method for the prevention and treatment of female stress urinary incontinence, worthy of further promotion.

Value of five-repetition sit-to-stand test in clinical evaluation of chronic obstructive pulmonary disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the value of five-repetition sit-to-stand test (5STS) in clinical evaluation of elderly patients with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Fifty-one patients with COPD and 20 healthy individuals were enrolled in this study. All the participants underwent 5STS, pulmonary function examination, and 6 min walking test (6MWT) and were evaluated for severity of dyspnea (by mMRC) and BODE index during the tests.</p><p><b>RESULTS</b>All the participants completed 5STS test with a good reproducibility of the time used for 3 sessions of the test (P<0.001). The mean time used by COPD patients for 5STS was significantly longer than that by healthy individuals (12.93±3.11s vs 0.72±0.71 s, P=0.002). The results of 5STS showed a significant negative correlation with those of 6MWT in the case group and control group with correlation coefficients of -0.611 and -0.682, respectively. The results of 5STS were negatively correlated with FEV1%Pre and body mass index (P<0.05) but positively with mMRC and BODE index in COPD patients (P<0.05).</p><p><b>CONCLUSION</b>5STS is a simple and reproducible test to evaluate the patients' exercise capacity and the severity of COPD, and is well correlated with the current methods for clinical evaluation of COPD.</p>

Clinical effect of honghua injection on hemorrheology in the prevention of deep venous thrombosis after operation of lower limb fracture / 中国生化药物杂志

Objective To investigate the clinical effect of honghua injection on hemorrheology in the prevention of deep venous thrombosis ( DVT) after operation of lower limbs fractures.Methods 100 cases with operation of lower limb fracture meeting the inclusion critera were randomly divided into two groups equally.Besides conventional treatment, the control group was treated with rivaroxaban, while the observation group was treated with honghua injection and rivaroxaban.The incidence of DVT, pro-inflammatory factors, hemorheology indices and adverse reactions were observed and compared. Results The observation group had a total DVT incidence of 10.0%, which was statistically lower than that of 28.0% in the control group(P<0.05). Three days after the operation, pro-inflammatory factors of TNF-α, IL-6 and IL-8 in the observation group was respectively statistically lower than that in the control group(P<0.05).As to hemorheology indices, in comparison with the control group, hematocrit, whole blood viscosity and fibrinogen in the observation group were statistically lower (P<0.05).During the treatment, there were no case of severe adverse reactions, and the incidence of adverse reactions in the two groups were statistically same.Conclusion Treatment of honghua injection in combination with rivaroxaban in the prevention of DVT is reliable, which could significantly reduce the incidence of DVT, alleviate inflammatory reaction and improve blood hypercoagulable state with minor adverse reactions.

[Progress in the study of core-crosslinked polymeric micelles in drug delivery system].

The core-crosslinked polymeric micelles were used as a new drug delivery system, which can decrease the premature drug release in blood circulation, improve the stability of the micelles, and effectively transport the drug into the therapy sites. Then the drug bioavailability increased further, while the side effect reduced. Most drugs were physically entrapped or chemically covalent with the polymer in the internals of micelles. Based on the various constitutions and properties of polymeric micelles as well as the special characteristics of body microenvironment, the environment-responsive or active targeting core-crosslinked micelles were designed and prepared. As a result, the drug controlled release behavior was obtained. In the present paper, the research progress of all kinds of core-crosslinked micelles which were published in recent years is introduced. Moreover, the characteristic and application prospect of these micelles in drug delivery system are analyzed and summarized.

Preparation and characterization of galactosylated glycol chitosan micelles and its potential use for hepatoma-targeting delivery of doxorubicin.

This study aimed to develop novel galactosylated cholesterol modified-glycol chitosan (Gal-CHGC) micelles for targeting delivery of doxorubicin (DOX) in live cancer cells. Three kinds of Gal-CHGC conjugates were synthesized and characterized. The mean particle size and critical aggregation concentration of these polymeric micelles increased with the increase of galactose substitution degree. The DOX-loaded micelles were prepared by an o/w method. The mean diameters of DOX-loaded galactosylated micelles were in the range of 387-497 nm. DOX released from drug-loaded micelles displayed a biphasic way. Cellular uptake studies demonstrated that DOX-loaded galactosylated micelles could enhance the uptake of DOX into HepG2 cells. Moreover, the cytotoxicity of DOX-loaded galactosylated micelles against HepG2 cells significantly improved in contrast with free DOX and DOX-loaded micelles without galactosylation. These results suggested that Gal-CHGC micelles could be a potential carrier for hepatoma-targeting drug delivery.

Progress in the study of core-crosslinked polymeric micelles in drug delivery system / 药学学报

The core-crosslinked polymeric micelles were used as a new drug delivery system, which can decrease the premature drug release in blood circulation, improve the stability of the micelles, and effectively transport the drug into the therapy sites. Then the drug bioavailability increased further, while the side effect reduced. Most drugs were physically entrapped or chemically covalent with the polymer in the internals of micelles. Based on the various constitutions and properties of polymeric micelles as well as the special characteristics of body microenvironment, the environment-responsive or active targeting core-crosslinked micelles were designed and prepared. As a result, the drug controlled release behavior was obtained. In the present paper, the research progress of all kinds of core-crosslinked micelles which were published in recent years is introduced. Moreover, the characteristic and application prospect of these micelles in drug delivery system are analyzed and summarized.

Preparation and anti-tumor effect in vitro of doxorubicin-loaded targeting micelles modified by folic acid / 中国药学杂志

OBJECTIVE: To prepare doxorubicin (DOX)-loaded micelles based on folic acid-modified cholesterol-glycol chitosan (FCHGC), and study its physicochemical properties and cytotoxicity in vitro. METHODS: FCHGC copolymer was synthesized by conjugating carboxyl groups of folic acid with the primary amino groups of cholesterol-modified glycol chitosan (CHGC) in the presence of coupling agent. FCHGC conjugate was characterized by 1H-NMR and fluorescence measurement using pyrene as a probe. The DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The size and shape of the micelles were analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). DOX release behavior was studied in vitro by a dialysis method in phosphate buffer saline (PBS, pH 7.4). The cytotoxicity and celluar uptake of drug-loaded micelles in vitro were investigated by 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. RESULTS: The critical aggregation concentration (CAC) of the FCHGC micelles in aqueous solution was 0.0163 mg·mL-1. Its particle size was 227 nm. The drug loading and encapsulation efficiency of DOX-loaded FCHGC (DFCHGC) micelles were 10.5% and 78.5%, respectively. The shape of DFCHGC micelles was almost spherical. DOX was released from DOX-loaded micelles in a biphasic manner, which displayed an initial rapid release phase and a later sustained release phase. The 50% inhibitory concentrations (IC50) of DOX, DOX-loaded CHGC (DCHGC) and DFCHGC micelles, incubated with folate receptor (FR)-negative A549 cells for 48 h, were 1.493, 0.620 and 0.974 μg·mL-1, respectively. Therefore, DCHGC micelles exhibited much more potent cytotoxicity against A549 cells than DFCHGC micelles. In FR-positive HeLa cells, the IC50 values of DOX, DCHGC and DFCHGC micelles were 1.398, 0.662 and 0.259 μg·mL-1, respectively. The DFCHGC micelles showed the greatest cytotoxicity among three DOX formulations for HeLa cells. And DFCHGC micelles exhibited greater cellular uptake than free DOX and DCHGC micelles in HeLa cells. CONCLUSION: The FCHGC micelles as a drug carrier for DOX delivery show selectively targeting to FR-positive cells, and improve the anti-tumor activity of DOX. These results suggested that FCHGC micelles could be a potential carrier for active targeting drug delivery.

Tissue distribution of doxorubicin-loaded nanoparticles based on cholesterol-modified glycol chitosan in S180-bearing mice / 中国药学杂志

OBJECTIVE: To study the tissue distribution of doxorubicin-loaded cholesterol-modified glycol chitosan nanoparticles (named as DCN-16) in S180-bearing mice. METHODS: After intravenous administration of doxorubicin (DOX) or DCN-16, DOX concentrations in plasma and tissues samples which were collected at predetermined time were determined by high performance liquid chromatography (HPLC). And DOX distribution and targeting performance in vivo were evaluated. RESULTS: DCN-16 displayed long circulation time in S180-bearing mice. The area under the curve (AUC0-∞) of DCN-16 was lower in heart (P < 0.05), lung (P < 0.05) and kidney (P < 0.05) than that of free DOX. In addition, compared with free DOX, DCN-16 also produced significantly increased drug accumulation in liver (P < 0.05), spleen (P < 0.05) and tumor (P < 0.05). The relative tissue exposure (Re) of DCN-16 in tumor was 2.56-folds of free DOX. CONCLUSION: Encapsulating DOX with cholesterol-modified glycol chitosan nanoparticles can prolong the systemic circulation time of DOX, increase its anti-tumor targeting activity and reduce its cardiac toxicity.

The research on the quality follow-up evaluation system of army clinical medicine masters / 中华医学教育探索杂志

Objective To provide evidences and suggestions for educational innovation in military medical universities. Methods To carry out follow-up survey and evaluation in 85 graduates by using questionnaire survey and apply evaluation index system for quality follow-up among military clinical medicine masters. Results The average score evaluated by graduates is 78.39, the average score evaluated by hospitals is 86.00, The two average scores are normally distributed and have a positive correlativity (r=0.495). Conclusion The integrative quality of graduate students is good, but they should strengthen further in clinical capability, general quality and independent innovation.

Polymeric nanoparticles of cholesterol-modified glycol chitosan for doxorubicin delivery: preparation and in-vitro and in-vivo characterization.

OBJECTIVES: Polymeric nanoparticles have been extensively studied as drug carriers. Chitosan and its derivatives have attracted significant attention in this regard but have limited application because of insolubility in biological solution. In this work, we attempted to utilize cholesterol-modified glycol chitosan (CHGC) self-aggregated nanoparticles to increase aqueous solubility, and to reduce side effects and enhance the antitumour efficacy of the anticancer drug doxorubicin. Methods CHGC nanoparticles were loaded with doxorubicin by a dialysis method, and their characteristics were determined by transmission electron microscopy examination, light-scattering study, in-vitro drug-release study, pharmacokinetic study in rats and in-vivo antitumour activity in mice. KEY FINDINGS: The resulting doxorubicin-loaded CHGC nanoparticles (DCNs) formed self-assembled aggregates in aqueous medium. From the observation by transmission electron microscopy, DCNs were almost spherical in shape. The mean diameters of these nanoparticles determined by dynamic light scattering were in the range of 237-336 nm as the doxorubicin-loading content increased from 1.73% to 9.36%. In-vitro data indicated that doxorubicin release from DCNs was much faster in phosphate-buffered saline at pH 5.5 than at pH 6.5 and 7.4, and the release rate was dependent on the loading content of doxorubicin in these nanoparticles. It was observed that DCN-16 (drug loaded content: 9.36%) exhibited prolonged circulation time in rat plasma and showed higher antitumour efficacy against S180-bearing mice than free doxorubicin. CONCLUSIONS: These results indicated that CHGC nanoparticles had potential as a carrier for insoluble anticancer drugs in cancer therapy.

Application of damage control orthopedics in 41 patients with severe multiple injuries.

OBJECTIVE: To probe the feasibility and efficacy of damage control orthopedics (DCO) in treating severe multiple injuries. METHODS: A retrospective analysis was made on the clinical data of 41 patients (31 males and 10 females, aged 18-71 years, mean: 36.4) with multiple injuries admitted to our department and treated by DCO from January 1995 to December 2005. RESULTS: As a first-stage therapy, devascularization of internal iliac arteries was performed in 29 patients with pelvic fractures combined with massive bleeding, including ligation of bilateral internal iliac arteries in 21 patients and embolization of bilateral internal iliac arteries in 8. And early external fixation of pelvis was performed in 10 patients. Ten patients with severe multiple injuries combined with femoral fractures were managed with primary debridement and temporal external fixation and 2 patients with spinal fractures combined with spinal cord compression received simple laminectomy. Thirty-one patients received definite internal fixation after resuscitation in intensive care unit. The overall mortality rate was 12.1% (5/41) with an average injury severity score of 41.4. The main causes of death were hemorrhagic shock and associated injuries. Complications occurred in 7 patients including acute respiratory distress syndrome in 3 cases, thrombosis of right common iliac artery in 1, subphernic abscess in 2 and infection of deep wound in lower extremity in 1. After treatment, all the patients got cured. CONCLUSIONS: Prompt diagnosis and integrated treatment are keys to higher survival rate in patients with severe multiple injuries. In this condition, DCO is an effective and safe option.

Application of damage control orthopedics in 41 patients with severe multiple injuries / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To probe the feasibility and efficacy of damage control orthopedics (DCO) in treating severe multiple injuries.</p><p><b>METHODS</b>A retrospective analysis was made on the clinical data of 41 patients (31 males and 10 females, aged 18-71 years, mean: 36.4) with multiple injuries admitted to our department and treated by DCO from January 1995 to December 2005.</p><p><b>RESULTS</b>As a first-stage therapy, devascularization of internal iliac arteries was performed in 29 patients with pelvic fractures combined with massive bleeding, including ligation of bilateral internal iliac arteries in 21 patients and embolization of bilateral internal iliac arteries in 8. And early external fixation of pelvis was performed in 10 patients. Ten patients with severe multiple injuries combined with femoral fractures were managed with primary debridement and temporal external fixation and 2 patients with spinal fractures combined with spinal cord compression received simple laminectomy. Thirty-one patients received definite internal fixation after resuscitation in intensive care unit. The overall mortality rate was 12.1% (5/41) with an average injury severity score of 41.4. The main causes of death were hemorrhagic shock and associated injuries. Complications occurred in 7 patients including acute respiratory distress syndrome in 3 cases, thrombosis of right common iliac artery in 1, subphernic abscess in 2 and infection of deep wound in lower extremity in 1. After treatment, all the patients got cured.</p><p><b>CONCLUSIONS</b>Prompt diagnosis and integrated treatment are keys to higher survival rate in patients with severe multiple injuries. In this condition, DCO is an effective and safe option.</p>

Liver trauma: experience in 348 cases.

Liver trauma, the main cause of death in patients suffering abdominal injury, remains an unresolved problem, especially in its most severe forms. The objective of this study was to probe effective surgical procedures and improve the outcome for patients with severe hepatic injury. A retrospective study of 348 patients with hepatic trauma seen in our institution during the past 12 years was carried out. Of these 348 patients, 259 (74.4%) underwent surgery. To manage severe liver trauma (American Association for the Surgery of Trauma grade III to grade V), procedures such as packing of the laceration with omentum, hepatectomy or direct control of bleeding vessels within the liver substance by means of the Pringle maneuver, selective hepatic artery ligation, retrohepatic caval repair with total hepatic vascular occlusion, and perihepatic packing were selected and combined based on the specific injury. In the 259 patients treated operatively, the survival rate was 86.9% (225/259); and 15 of 40 with retrohepatic venous injury (RHVI) were cured with the maximum blood transfusion of 60 units. In 42 patients treated by perihepatic packing, the bleeding was stopped in 20 of 25 (80%) with RHVI and in 14 of 17 (82%) without such injury ( p > 0.75). The percentage of failure of nonoperative management was 17.2% (17/99); and it was 46.7% (14/30) in patients with grade III-V injury. Death occurred in 3 (50%) of 6 failures of grade IV-V injury. The overall mortality rate was 11.8% (41/348), and 51% of the deaths were due to exsanguination. The results suggest that severe hepatic injuries, especially grade IV-V injuries, usually require surgical intervention; reasonable surgical procedures based on classification of liver trauma and combined application of techniques can increase the survival rate; and perihepatic packing is effective in dealing with RHVI.

[Management of extensive closed internal degloving injury].

OBJECTIVE: To study the management of extensive closed internal degloving injury (CIDI). METHODS: From September 1987 to October 1999, 18 cases of CIDI were retrospectively reviewed. Of 18 cases, there were 7 cases in thigh, 6 cases in legs and 5 cases in pelvis, ranging from 15 cm x 12 cm to 38 cm x 25 cm in size. Various managements were adopted according to the severity of the injury, including vacuum drainage and adjuvant compression in 5 cases, regrafting of defatting fenestrated full-thickness skin by non-resection in 8 cases, and skin grafting with transfer of myocutaneous flap in 5 cases. Among them, there were 11 cases of bone and articular fixation or repair, 4 cases of principal vessels repair. All of the cases were evaluated clinically and followed up for 6 months to 3 years. RESULTS: In the 8 cases repaired by regrafting of defatting fenestrated full-thickness skin, only one case of skin necrosis, 5 cm x 2 cm in size, recovered after skin grafting; the others healed well. All of the patients recovered normal life and had normal limbs. CONCLUSION: It's crucial to make a careful assessment about the injury severity of CIDI, to stress on importance of management of both CIDI and deep injury, and to choose proper options after comprehensive assessment of the injury.