Abstract:Objective:To determine meloxicam concentrations in both plasma and extract solution of tested-skin in SD rats and the fluorescence intensity,location of fluorescein sodium salt (NaFI) in striped rat skin within 4 h after transdermal administration,so as to investigate the enhancing effect of negative electret on percutaneous absorption of meloxicam and percutaneous absorption route of NaFI.Methods: Pharmaceutical method and grid-controlled constant corona charge technique were used to prepare electret meloxicam patch.High performance liquid chromatography (HPLC) method was employed to determine meloxicam concentration after transdermal administration.NaFI was used as probe to determine the localization and percutaneous absorption route of NaFI by using laser scanning confocal microscopy (LSCM).Results: (1)Negative electret and its polypropylene(PP) electret meloxicam patch exhibited a good charge storage stability.(2)The results of HPLC demonstrated that electret had a remarkable enhancing effect on percutaneous absorption of meloxicam after application for 1-4 h.(3)LSCM further proved the enhancing effect of negative electret on percutaneous absorption of small molecules.We also found that the stratum corneum and the hair follicle areas were the two main pathways for the enhancing effect of the electret.Conclusion: Negative electret can be used as an enhancer for transdermal permeation of meloxicam.

Abstract:Objective:To study the enhancing effects of electret on transdermal delivery of lidocaine patches in vitro.Methods:In vitro rat skin permeation experiment was carried out with lidocaine patches,lidocaine paches with azone,positive/negative electret lidocaine patches,and positive/negative electret lidocaine patches with azone by using Franz diffusion cells.The accumulated lidocaine concentrations in rat skin treated with each kind of patches were examined by HPLC to investigate the influence of electret on transdermal delivery of lidocaine.Results:(1) The enhancement rates of 1%,3% and 5% azone lidocaine patches 10 h after application were 1.06,1.10 and 1.66 folds (P<0.05,5% azone vs lidocaine patch group) that of the lidocaine patch,respectively.(2) Lidocaine patches with negative electret containing 1%,3% and 5% azone showed similar transdermal behavior to the corresponding chemical enhancer patches.(3) Lidocaine patches with positive electret containing 1%,3% and 5% azone showed much better enhancing effect than the corresponding chemical enhancer lidocaine patches (P<0.05). Besides,5% azone together with positive electret showed a cooperative enhancing effect.Conclusion:Positive electret patch has better effect in enhancing transdermal delivery of lidocaine.Besides,the cooperative enhancing effect of azone with positive electret on transdermal delivery of lidocaine is in a concentration-dependent manner with azone.

Abstract:Objective:To study charge storage stability of electret film made of polypropylene(PP)/porous polytetrafluoroethylene(PTFE)/polypropylene composite.Methods: The PP/porous PTFE/PP composite electret film was prepared with porous PTFE,polyethylene(PE) and PP by heat melting technique.The charge storage stability of the electret film and transportation were evaluated by using the methods of isothermal surface potential attenuation and open-circuit thermally stimulated discharge (TSD) current spectra.Results:(1) The charge storage stability of PP/porous PTFE/PP composite electret was superior to that of PP electret made under ordinary temperature,because the space charge of PP/porous PTFE/PP electret was transferred from deep trap to flat trap during the heat melting process.(2) Satisfactory charge storage stability was observed in PP/porous PTFE/PP electret when under the condition of high humidity.Conclusion:PP/porous PTFE/PP electret film has satisfactory charge storage stability and can be used as a novel enhancer in transdermal delivery of drugs.

Abstract:Objective:Currently most researches concerning electret transdermal patches are performed by one-factor experimental design with relatively poor efficiency. To analyze the influencing factors in a more systematical and effective manner,we put forward an optimized design for in vitro experiment with electret transdermal patches. Methods:Due to the great number and various levels of factors impacting the charge storage stability of electrets,we combined uniform design and orthogonal design to optimize the screening for the stable transdermal patch. In the following in vitro study,we optimized the design of percutaneous experiments to screen for charge polarity and penetration enhancers using a two-factor experimental design. And using an orthogonal experimental design,we further studied the influence of different levels of main drug,surface potential and penetration enhancer on transdermal absorption.Conclusion:The present design,taking into consideration of various factors and using multi-factor experimental design,can more effectively analyze data,reduce workload,and is feasible.

Abstract:Objective:To isolate and identify cancer stem cells from esophageal cancer cells (ECCs) using cell surface marker p75NTR.Methods: ECCs were cultured from surgically resected ECC specimens; ECC cell lines TE-1 and Eca109 were also cultured.The expression of p75NTR in human ECCs was examined by flow cytometry.p75NTR positive cells were isolated from ECCs using magnetic activated cell sorting (MACS) method.The proliferation,differentiation,and the ability of colony-forming in soft agar of the p75NTR positive cells were observed.The p75NTR positive cells were injected into BALB/c nude mice subcutaneously to observe their tumorigenesis ability.The survival rates of p75NTR positive and negative cells were assessed after treated with chemotherapy drugs to evaluate the resistance of p75NTR positive cells.Results: Six out of the eight cell lines,including SHEC-4,SHEC-6,SHEC-7,SHEC-8,Eca109,and TE-1,were positive of p75NTR ,with the positive rates being 2.71%,0.32%,3.35%,1.13%,2.15%,and 0.45%,respectively.It was showed that p75NTR positive cells possessed higher proliferation ability compared with p75NTR negative cells (P＜0.01).The p75NTR positive cells had higher colony-forming ability in soft agar compared with p75NTR negative cells (P＜0.01).The p75NTR positive cells demonstrated stronger tumorigenesis ability in nude mice. As few as 2 000 SHEC-7 cells could give rise to new tumors in xenotransplantation,with a tumorigenesis ability 50 times as high as that of the p75NTR negative cells.When treated with chemotherapy drugs for 48 h,p75NTR positive cells had significantly higher survival rate than p75NTR negative cells (P<0.05).Conclusion: The p75NTR positive ECCs possess self-renewal,differentiation,and proliferation abilities; they are strongly resistant to chemotherapy drugs,which gives them strong tumorigenesis ability and the characters of tumor stem cells.

Abstract:Objective:To determine the expression of AC133 and EpCAM in human pulmonary adenocarcinoma by dual immunofluorescent labeling technique and to isolate AC133+EpCAM+ cells by flow cytometry,so as to provide a basis for further investigation of human pulmonary adenocarcinoma stem cells.Methods:The human lung adenocarcinoma tissues were obtained and subjected to cryosection and dual immunofluorescent staining.AC133+EpCAM+cells in human pulmonary adenocarcinoma were identified by using laser confocal microscopy.The fresh adenocarcinoma tissues were prepared into single cell suspension with the collagen and red blood cell removed.AC133 and EpCAM were used to label cells and the AC133+EpCAM+cells were isolated by flow cytometry.Results:AC133+EpCAM+ cells were found in human pulmonary adenocarcinoma and they could be isolated by flow cytometry.Conclusion:The existence of AC133+EpCAM+ cells has been confirmed in the lung adenocarcinoma tissues; the double positive cells can be isolated by flow cytometry,which provides a basis for further investigation of lung cancer stem cells.

Abstract:Objective:To construct and identify adenovirus vector containing the chromogranin A 1-76 segment (CGA1-76),or vasostatin-1 (VS-1) gene,and to observe its expression in cardiomyocytes of rats, so as to investigate the protective effects of VS-1 transgenic therapy on myocardial hypoxia/reoxygenation (H/R) injury. Methods:(1) The primers of CGA1-76 cDNA was designed and used for PCR amplification. The products were then cloned into adenovirus shuttle plasmid pAdTrack and linearized by enzyme Pme Ⅰ; the resultant plasmid was co-transfected into E.coli BJ5183 cells with adenovirus backbone plasmid pAdEasy-1 for homologous recombination. Then the recombinant plasmid was identified,linearized and packaged with QBI-293A cells to amplify the recombinant adenovirus Ad-VS-1,which was then used to infect H9c2 cardiomyocytes. Western blotting was used to detect the expression of VS-1 protein expression. (2)Myocardial H/R model was established and the cells were divided into 4 groups:blank group,H/R group,mock infection + H/R group,and Ad-VS-1 infection + H/R group. The viability of cardiomyocytes,the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were measured. Results:(1) The recombinant plasmid was constructed successfully as confirmed by PCR,sequencing and enzyme digestion. Western blotting confirmed the protein expression of VS-1 in the H9c2 cells. (2)The viability of cardiomyocytes and the activity of SOD in H/R group were obviously lower than those of the blank group; the level of MDA was higher than that of the blank group. Transfection with VS-1 increased the cardiomyocytes viability and SOD activity in the H/R model group and decreased the production of MDA. Conclusion:Ad-VS-1 has been successfully constructed,and transfection with it can protect rat cardiomyocytes from H/R injury,which is related to the anti-oxidation process.

Abstract:Objective:To investigate the influence of RNA interference targeting PI3K p85α on the invasion and metastasis of colorectal cancer cells.Methods:Four shRNA vectors and one negative control vector were designed and stably transfected into LoVo cells.Western blotting analysis was used to screen for the group which had the highest inhibitory rate;the cells were subjected to wound closure assay and transwell assay to determine the migration of LoVo cells after stable transfection.Results:Western blotting analysis showed that cells transfected with shRNA/324 vector had the strongest inhibition of PI3K p85α protein,with the inhibition rate being 77%,and cells in this group were used for wound closure assay and transwell assay.Wound closure assay showed that the healing ability of PI3K p85α-depleted cells was significantly lower than that of the control cells (P<0.05).Transwell assay showed that the cells passing the polycarbonate membranes was significantly less in PI3K p85α-knockdown cells than in the control cells (P<0.05).Conclusion:Depletion of PI3K p85α protein can obviously inhibit the migration of LoVo cells.PI3K p85α may be a new therapeutic target for treatment of colorectal cancer metastasis.

Abstract:Objective:To prepare magnetic poly D,L-lactide-co-glycolide oxymatrine nanoparticle(M-PLGA-OM-NP) and investigate its preventive effects against experimental liver fibrosis.Methods: The M-PLGA-OM-NP was prepared by multiple emulsion process and observed by transmission electron microscope(TEM).Dimethylnitrosamine (DMN)-induced liver fibrosis was established with mice.After intervention with M-PLGA-OM-NP,the expression of α-smooth muscle actin (a-SMA) in the livers of mice was detected by immunohistochemical assay and the score of liver fibrosis was determined by H-E staining and Van Gieson (VG) staining.Results: The prepared M-PLGA-OM-NP was in a regular sphere shape,with a mean diameter of 146.5 nm; the drug loading was 7.61% and the encapsulation ratio was 44.8%.The serum Alt level in the M-PLGA-OM-NP group was decreased compared with that in the model group.Light microscopy revealed that the fibrosis in the M-PLGA-OM-NP group was greatly improved compared with the model group and pure oxymatrine group.The expression of a-SMA,the marker of hepatic stellate cell activation,was obviously decreased in the M-PLGA-OM-NP group compared with that in the other groups.Conclusion: The prepared M-PLGA-OM-NP under magnetic field can reinforce the preventive effect of oxymatrine against DMN-induced experimental liver fibrosis in mice.

Abstract:Objective:To prepare killer peptide-loaded PLGA nanoparticles which have better effect in treating systemic crypotococcosis.Methods: We adopted a modified double-emulsion method to prepare the killer peptide-loaded PLGA nanoparticles,and the nanoparticles were characterized by using TEM,SEM,Dynamic Laser Scattering,drug loading analysis,ecapsulation efficacy assessment and in vitro release test.We also evaluated the antifungal activities of killer peptide and killer peptide-loaded PLGA nanoparticles against Cryptococcus neoformans ATCC32609 by plate count method.In the in vivo study,the anticryptococcal efficacies of killer peptide and killer peptide-loaded PLGA nanoparticles were compared by observing the survival and colony-forming in vital organs in a systemic murine cryptococcosis model.Results: We successfully synthesized killer peptide-loaded PLGA nanoparticles.In vitro anticryptococcal test showed that the killer peptide and killer peptide-loaded PLGA nanoparticles had significantly stronger anticryptococcal effect compared with the normal saline group (P<0.05),and there was no significant difference in the efficacies between free killer peptide and killer peptide-loaded PLGA nanoparticles (P>0.05).In vivo test demonstrated that mice treated with killer peptide-loaded PLGA nanoparticles (3 mg/kg or 5 mg/kg) had longer survival period and less fungal burden in vital organs than mice treated with free killer peptide (P<0.05); there was no significant difference in fungal burden and survival period between empty PLGA nanoparticle treated group and normal saline group (P>0.05).Conclusion: The killer peptide-loaded PLGA nanoparticles are more effective in treating systemic murine cryptococcosis.

Abstract:Objective:To study the role of vascular endothelial growth factor(VEGF) in vein sheath prevention of arterial bypass graft stricture and the efficacies of vein sheath of different diameters. Methods: The vein grafts and their specimens were obtained via animal experiment of sheath intervention. Immunohistochemistry method was used to examine the expression of VEGF and proliferating cell nuclear antigen (PCNA) and the status of nutrient vessel in the specimens,so as to investigate the function of VEGF. Results: Compared with the control group,the vein sheath intervention group had significantly lower VEGF content in the media (P<0.05) and higher content in the adventitia (P<0.05); it also had lower PCNA content in the media (P<0.05) and increased blood vessel density in the adventitia (P<0.05). Conclusion: Vein sheath can effectively increase the distribution of VEGF in the adventitia and decrease its distribution in the media and intima,thus promoting the growth of nutrient blood vessels and decreasing media hyperplasia and re-stenosis.

Abstract:Objective:To observe the influences of sleep deprivation and antioxidant agent α-lipoic acid on the expression of IRE1 in the cortex and hippocampus in rats.Methods: Rats were randomly divided into control groups and sleep deprivation group.The control groups included blank control group (n=10) and environmental control group (n=10).Sleep deprivation group included 120 rats,and rats were further divided into α-lipoic acid group (25 mg·kg-1·d-1) and sleep deprivation model group.The two were further divided into 6 groups according to the periods of sleep deprivation and sleep restoration (SD 1 d,SD 3 d,SD 5 d,SD 7 d,SD 7 d/RS 6 h,SD 7 d/RS 12 h\[n＝10\]）.The expression of IRE1 mRNA and protein was examined by RT-PCR and immunohistochemistry,respectively.Results: RT-PCR results showed that the expression of IRE1 mRNA in the cortex and hippocampus were significantly higher in sleep deprivation group than in the blank and environmental control groups (P<0.05); there was no significant difference between the latter 2 groups.α-lipoic acid decreased the expression of IRE1.Expression of IRE1 between α-lipoic acid groups and sleep deprivation model groups was significantly different on SD 5 d,SD 7 d,SD 7 d/RS 6 h and SD 7 d/RS 12 h（P<0.05）.The immunohistochemistry results of IRE1 expression were consistant with RT-PCR results.Conclusion: α-lipoic acid can reduce the cerebral IRE1 expression in sleep deprivation rats,which provides a basis for antioxidant treatment of sleep deprivation.

Abstract:Objective:To explore the roles of mammalian target of rapamycin (mTOR) and the activated mTOR (phosphorylated mTOR,p-mTOR) in the development and progression of colorectal cancer,and to discuss the clinical significance.Methods:The expression of mTOR and p-mTOR in 185 colorectal cancer specimens and the corresponding adjacent tissues were evaluated by tissue microarray and immunohistochemistry,and the relationship between the expression and the age,sex,invasion depth(T stage),lymph metastasis,TNM stage and differentiation degree was analyzed.Results:Diffused expression of mTOR and hardly any expression of p-mTOR were found in the adjacent tissues.The expression of mTOR and p-mTOR was obviously stronger in the colorectal cancer tissues compared with that in the adjacent tissues.The over-expression rates of mTOR and p-mTOR in colorectal cancer were 45.9% and 42.2%,respectively.There was no significant correlation of mTOR and p-mTOR over-expression with age,sex(P>0.05); the over-expression of mTOR was correlated with the differentiation degree (P<0.05),but not with the invasion depth (T stage),TNM stage,or lymph metastasis (P>0.05).The correlation of p-mTOR over-expression with the invasion depth (T stage),lymph metastasis and TNM stage was significant (P<0.05),but that with the differentiation degree was not significant (P>0.05).Conclusion:Over-expression of p-mTOR is closely associated with the malignant phenotype of colorectal cancer.It is also indicated that p-mTOR may be involved in the development and progression of colorectal cancer.

Abstract:Objective:To observe the anti-tumor effect of adoptive immunotherapy with CTL induced by PSA-pulsed dendritic cell vaccine against prostate cancer in mice.Methods: Nude mice were s.c.inoculated with LNCaP tumor cells to establish prostate cancer model.CTL induced in vitro by different peptide-pulsed dendritic cells (Non-DC,Ova-DC,Lys-DC and PSA-DC) were used for adoptive immunotherapy of experiment nude model through vena caudalis on d 15 and d 22 after inoculation.The survival of nude mice and the sizes of tumors were observed with d 50 after the initial treatment as the endpoint.Results: The tumor sizes in Non-DC,Ova-DC,Lys-DC and PSA-DC groups on d 30 and d 50 after adoptive immunotherapy were significantly larger than that at d 15 after inoculation (P<0.01).The tumors sizes in Lys-DC and PSA-DC groups were significantly smaller than those in the Non-DC and Ova-DC groups（P<0.01）.The survival periods of animals in Lys-DC and PSA-DC groups were significantly longer than those in the Non-DC and Ova-DC groups (P<0.01）.Conclusion: Adoptive immunotherapy with CTL induced by DC-based PSA vaccine can inhibit the growth of prostate cancer LNCaP cells in nude mice and increase the survival of the animals.

Abstract:Objective:To establish a quantifiable and easily manipulable mouse model of liver regeneration by partial hepatectomy,so as to provide a basis for investigating the underlying cellular and molecular mechanisms and pathophysiological significance of liver regeneration.Methods:Normal adult C57BL/6 mice were fixed by cardiac perfusion,the liver lobes were dissected and weighed,and the proportions of each lobe were calculated.Under anesthetic and sterile condition,partial hepatectomy was performed by removing the left lateral,left middle,and right middle liver lobes in turn to establish the regeneration model.The activation of alpha-fetoprotein (AFP) gene in the regenerating liver was dynamically monitored by real-time PCR analysis.Results:The left lateral,left middle,and right middle liver lobes together accounted for approximately 70% of the total liver weight.The animals survived and lived well after removal of the three lobes in turn.RT-PCR showed that AFP expression was activated in the regenerating livers.Conclusion:We have successfully established the mouse model of liver regeneration by consecutive partial hepatectomy.This method can quantify the heptectomy and is easy to perform,which lays a foundation for studying liver regeneration in mice.

Abstract:Objective: To investigate the protective effect of erythropoietin (EPO) on the acute renal injuries caused by abdomen open injury plus seawater immersion in rats.Methods: Sixty healthy male Wistar rats (clean grade) were evenly randomized into four groups,namely,EPO pre-treatment group,observation group,low-dose EPO treatment group and high-dose EPO treatment group.Acute renal injury was induced by abdomen open injury plus artificial seawater immersion (22℃).The serum creatine,BUN,creatine kinase,creatine kinase isoenzyme,TNF-α,IL-6,complement C3a,C-reactive protein,renal homogenate superoxide dismutase (SOD),and the renal pathological changes were observed and compared between different groups.Results: Acute renal injury was observed in all groups 3 hours after abdomen open injury plus seawater immersion,with increased serum creatine and BUN,but the rats survived after treatment.The serum creatine,BUN,creatine kinase,and creatine kinase isoenzyme in EPO pre-treatment group were significantly lower than those of the other 3 groups; the levels of TNF-α,IL-6,complement C3a,and C-reactive protein were also obviously decreased; the renal homogenate SOD was obviously increased; and the score of renal proximal tubule necrosis was obviously decreased.However,no significant differences were found between the high- and low-dose EPO groups concerning all the parameters (P>0.05).Conclusion: EPO pre-treatment has a protective effect on the acute renal injury induced by abdomen open injury plus seawater immersion in rats.

Abstract:Objective:To simulate the surgical approaches for intracranial aneurysms using three-dimensional CT angiography (3D-CTA),so as to assess the value of 3D-CTA in the microneurosurgery for ruptured intracranial aneurysms.Methods: Totally 134 patients with spontaneous subarachnoid hemorrhage caused by ruptured intracranial aneurysm were confirmed by operation.All the patients were examined by CTA before operation and surgical simulation was conducted.Some patients were examined by the pre-operative DSA (digital subtract angiography).The findings of pre-operation CTA,DSA and intra-operative findings were compared and the clinical value of cerebral 3D-CTA was analyzed.Results: 3D-CTA discovered 162 aneurysms out of a total of 163 in 134 patients. The sensitivity and specificity of 3D-CTA for diagnosis of ruptured intracranial aneurysm were 99.4% and 100%,respectively.Moreover,pre-operation examination with 3D-CTA clearly displayed the location,size,and shape of aneurysms,the axis direction of the aneurysmatic summits and the width of aneurysmatic neck.Furthermore,the spatial relations between the parent aneurysm artery,the aneurysm,the periphery vessel and bony structures were also demonstrated.These findings were in accordance with the intra-operative findings.There was no rupture during exploration. The Glasgow outcome score was 5 in 85 patients,4 in 22,3 in 17,2 in 6,and 1 in 4.Conclusion: The conventional pre-operative 3D-CTA examination can simulate surgery for patients with ruptured intracranial aneurysms,and it can help to design the operative approach and improve the successful rate of operation.

Abstract:Objective:To explore the application and efficiency of unilateral vertebral plate decompression,interbody fusion and pedicle screw fixation in treatment of lumbar disc herniation. Methods:From Feb. 2006 to Feb. 2008,24 patients underwent unilateral vertebral plate decompression,interbody fusion and pedicle screw fixation. The patients were followed up for one year and the following data were recorded:operation time,estimated blood loss,duration of hospital-stay,short-term and medium-term clinical outcome. Results:All patients had their low back pain and/or lower extremity radicular pain improved during the one year follow-up. The last follow-up showed that the numbers of patients with Oswestry Disability Index(ODI) P0-P5 were 5,11,6,2,0,and 0,respectively. The clinical outcomes determined by modified JOA criteria showed that 18 patients had excellent outcomes,4 had good outcomes,and 2 had fair outcomes,with the excellent and good outcomes occupying 91.67%. Conclusion:The unilateral fixation can be used in patients with lumbar disc herniations who need lumbar spinal fusion. The medium-term outcomes is satisfactory.

Abstract:Objective:To investigate the relationship of TNF-A-863 and CGRP979 gene polymorphisms with the susceptibility to severe chronic periodontitis in Chinese.Methods: Buccal swabs were collected from 100 adult patients with severe chronic periodontitis and 118 healthy adult controls.DNA was extracted from each subjects of the two groups.PCR-LDR technique was used to identify the genotypes of TNF-A-863 and CGRP979.The difference in the genotypes between the two groups was analyzed by statistics software.Results: The genotype of TNF-A-863 was mainly TNF-A-863 A/C in patients with severe chronic periodontitis and TNF-A-863 C/C in healthy controls.There were significant differences in TNF-A-863 distribution between the two groups(P<0.05).We also found that there were significant differences in genotype distribution of CGRP979 between the two groups (P<0.05),with A/G predominating in patients with severe chronic periodontitis.Conclusion: TNF-A-863 polymorphism is associated with severe chronic periodontitis; A/G of the CGRP979 loci might be a factor for severe chronic periodontitis.

Abstract:Objective:To summarize our experience on the diagnosis and surgical treatment of primary retroperitoneal tumor(PRPT).Methods: The clinical data of 315 patients with primary retroperitoneal tumor (from Jan. 2000 to Jun. 2008) were retrospectively analyzed,and the clinical experience on diagnosis and treatment was summarized.Results: The ratio of benign to malignant tumors in our group was 0.55∶1.Totally 294 patients received operation,including 161 cases of radical resection,69 cases of combined resection,and 64 partial palliative resection. Twenty-one patients received no operation. The prognoses of patients who received radical resection for malignant tumors were significantly improved compared with those of patients who received partial palliative resection (P<0.05).Conclusion: Imaging diagnosis can effectively identify PRPT. Complete resection is the key for treatment of PRPT,and reoperation is an effective treatment for recurrent PRPT.

Abstract:Objective:To establish a RP-HPLC method for determining the plasma concentration of nonoxynol-9 and to apply the method in studying the pharmacokinetics of nonoxynol-9 in healthy female rabbits. Methods: A single dose of nonoxynol-9 (64 mg to each animal) was given to 6 healthy female rabbits (weighing 2.0-2.2 kg) via vagina. The plasma samples were collected and the concentrations of nonoxynol-9 were determined by RP-HPLC method using DiamonsilTM ODS column (200 mm×4.6 mm,5 μm) and mobile phase of methanol-water (955) at a flow rate of 1.0 ml/min. The excitation and emission wavelengths were 226 nm and 300 nm,respectively. The column temperature was 30℃.The pharmacokinetic parameters were calculated. Results: The calibration curve of nonoxynol-9 showed good linearity over the range of 0.05-5.00 μg/ml; both the intra- and inter-day precisions were lower than 10%. The recovery rates at three concentrations (0.10,0.50,and 2.00 μg/ml) were (101.67±8.12)%,(100.84±5.42)%,and (100.29±3.81)%,respectively. The main pharmacokinetic parameters of nonoxynol-9 were as following: t1/2 (3.75±0.87) h,tmax (3.2±0.4) h,Cmax (2.75±0.32) μg/ml,AUC0-12 (12.72±2.14） μg·h·ml-1,AUC0-∞ (15.05±2.84）μg·h·ml-1,and MRT (6.85±1.13) h. Conclusion: The established method is convenient,sensitive and specific,and can be used for determination of plasma nonoxynol-9 concentration and for its pharmacokinetic studies in rabbits.

Abstract:Objective:To evaluate the relative efficiency of pharmacies in military hospitals,so as to provide evidence for rational allocation in medicinals resources in hospitals. Methods:Data envelopment analysis (DEA) was used to evaluate relative efficiencies of 71 pharmacies in military hospitals (also as decision making units,DMUs). The input factors included pharmacy personnels,equipment,areas of pharmacies,and development funds; the output factors included drug charge,clinical pharmaceutical service,pharmaceutical information service,academic achievements and research activities. Decomposition of the pharmacy efficiencies under different economic conditions was performed to evaluate the scale efficiency (SE),the resource disposal efficiency (DE) and the technical efficiency (TE). Pearson correlation analysis and chi-square test were used for statistic analysis. Results:DEA results showed that the relative efficiency of the 28 pharmacies was 1, they were DEA effective; the relative efficiency of the 43 DMUs was less than 1,indicating the presence of efficiency loss. Multiple linear regression analysis showed that hospital grade,bed number,clinical time of pharmacists,HR flow-in rate,proportions of pharmacists with undergraduate or graduate diploma,bed utilization rate,etc. were correlated with the 5 output factors. Five multiple linear regression equation were established. We also found that the distribution of pharmacies of SE,DE,and TE non-efficiency were significantly different between hospitals of different grades; the distribution of pharmacies of DE, and TE non-efficiency were significantly different between hospitals located in different regions. Pearson correlation analysis showed that the DEA efficiency of pharmacies was correlated with hospital grade,not with the area or the city where the hospitals located. Conclusion:The grades of military hospitals and the subsequent effective allocation of resources and technologies may be the key factor to increase the efficiencies of pharmacies.

Abstract:Objective: To design a portable real-time monitoring tool for spine surgery and to preliminarily evaluate its application, so as to reduce the iatrogenic injury during the treatment of battle field spinal cord injury. Methods: A portable spine guiding device for spinal fixation was designed and prepared. The spinal specimens were randomly divided into control group (n=10) and experimental group (n=10). In the control group the way was cleared for the pedicle according to the doctor's experience; in the experimental group the way was cleared using our self-designed guiding device. The operation time was recorded in the two groups. After manipulation the specimens were opened along the pedicle level; the location and the depth of the needle were compared. Results: The manipulation time of a single vertebral body was (0.5±0.2) min in the control group and (0.6±0.1) min in the experimental group (P>0.05). The edge of the puncture to the pedicle wall in the control group was significantly shorter than that in the experimental group([1.1±0.3] vs [1.8±0.2]mm,P=0.037).Conclusion:The designed portable guiding device for spinal fixation is easy to carry, simple to operate; and initial in vitro application is satisfactory and can provide reliable reference for early operation.

Abstract:Objective:To report our experience on endoscopic nasal lateral wall dissection approach for treatment of refractory benign maxillary sinus diseases.Methods:The data of 8 patients,who had relapsing maxillary diseases 2 to 4 times after maxillary sinus or ethmoid sinus surgery, were retrospectively analyzed. The patients included 6 males and 2 females,with an average age of (55±14) years（41-69 years）. Under general anesthesia the operation started from an incision in front of the inferior turbinate (IT),then the lacrimal duct(LD) was dissected to form a IT-LD flap. The flap was placed inwardly and the maxillary sinus lesion was removed under endoscope. The inferior antrostomy was performed when necessary. The possibility of maxillary sinus malignant lesions was ruled out by postoperative pathology.Results:Postoperative pathological findings confirmed that the lesions were all benign. The follow-up period ranged from 6-14 months. Five patients were cured and 3 were improved 6 months after operation.There were no complications such as cheek numbness,epiphora,orbital hemorrhage,visual disorder or cerebrospinal fluid rhinorrhea during follow-up.Conclusion:The endoscopic nasal lateral wall dissection approach provides a wider vision field and allows for a thorough removal of maxillary sinus lesions,while reserving the LD and IT.

Abstract:Objective：To apply 1HNMR spectroscopic analysis and principal components analysis(PCA) for investigating the fluctuation of metabolites between hydrocortisone-induced kidney deficiency syndrome(Shenxu Zheng) rats and the normal rats.Methods: Using 1HNMR based metabolic profiling and PCA,we investigated the difference of urine metabolites between the normal rats and rats with hydrocortisone-induced kidney deficiency syndrome.We also explained the changes of the related metabolic pathway or metabolic network.Results: The changes following hydrocortisone intervention of rats could be identified by PCA,and the kidney deficiency syndrome rats entered a state of “hyperfunction”,involving a series of changes in metabolic pathway and metabolic network.The response integral area of lactic acid(δ 1.37) increased，indicating the accumulation of metabolites of lactic acid.The amount of dimethylamine(δ 2.72) also increased,indicating that the disorder of kidney function was related to kidney-deficiency syndrome.The response of creatinine(δ 3.87),asparaginic acid(δ 2.83),taurine(δ 3.44,3.28),and hippurate(δ 7.84,7.56,7.64,3.97) all decreased significantly,indicating that the hydrocortisone might cause adrenal cortex excretion injury.The response integral area of succinate(δ 2.41) and citric acid(δ 2.53,2.68) decreased,which was usually caused by disorder of the mitochondrial function.Conclusion: It is suggested that the metabonomic approach can be used to investigate the pathophysiological changes under certain physiopathologic conditions.This study provides evidence for understanding “Shenxu Zheng”(kidney deficiency syndrome) in traditional Chinese medicine and for diagnosis and therapy of such diseases.

Abstract:Hypotha is the center of energy homeostasis in the organism.The central step of its endocrinology regulation network is that it can receive the leptin signal provided by peripheral adipose tissues,and subsequently modulate the expression of Agouti-related protein (AgRP) and proopiomelanocortin (POMC),maintaining energy homeostasis by regulating energy intake and consumption.Transcription factors FoxO1 and STAT3(signal transducer and activator of transcription 3) are key molecules in leptin-mediated transcriptional regulation of AgRP; they directly participate in the regulation of energy homeostasis.FoxO1 can enhance AgRP expression and activated STAT3 can inhibit AgRP expression.Leptin can modulate AgRP and energy homeostasis through inhibiting FoxO1 activity and activating STAT3.The article reviews the regulatory mechanism of leptin upon AgRP.

Abstract:Renal artery aneurysms are rare and surgical intervention is difficult due to complicated anatomy.Endovascular techniques make it easier for vascular surgeons,but the long-term outcomes remain to be observed.This article reviews the current status,advancements and existing problems in diagnosis and treatment of renal artery aneurysms.

Abstract:目的:观察重组人肝再生增强因子(recombinant human augmenter of liver regeneration,rhALR)对梗阻性黄疸大鼠肝细胞线粒体转录因子A(mitochondrial transcription factor A,TFAM)及核呼吸因子1(nuclear respiratory factor-1,NRF-1)表达的影响。方法:健康Wistar大鼠随机分为假手术(Sham)组、胆道梗阻再通(BDO-RBF)组、胆道梗阻再通及rhALR治疗(BDO-RBF-rhALR)组(n=48),利用荧光定量PCR方法检测各组大鼠肝细胞TFAM、NRF-1 mRNA的表达。结果:当胆道梗阻后,大鼠肝细胞TFAM、NRF-1 mRNA表达均下降(P<0.05),且随着梗阻时间的延长其下降程度逐步增加；解除梗阻后,其拷贝数逐步恢复。BDO-RBF-rhALR组大鼠TFAM、NRF-1 mRNA表达明显高于同一时间点BDO-RBF组(P<0.05)。结论:腹腔注射rhALR可能通过促进梗阻性黄疸大鼠肝细胞TFAM、NRF-1 mRNA表达发挥保护肝功能的作用。

Abstract:目的:运用简易智能精神状态检查量表(mini-mental state examination,MMSE)和药物脑电图功率谱技术观察盐酸美金刚治疗轻、中度阿尔茨海默病(AD)的近期疗效。方法:记录分析20例轻、中度AD患者口服盐酸美金刚治疗前、治疗4周后、治疗8周后的MMSE和脑电功率谱变化情况。结果:盐酸美金刚治疗4周和8周后患者地点定向、瞬时记忆、短程回忆值及总分较治疗前明显升高(P<0.01)。盐酸美金刚治疗4周后，除右颞区外的其他脑皮质区θ频带功率值较治疗前均明显下降，左枕区α2频带功率值较治疗前明显增高 (P<0.05)；治疗8周后，右顶区δ频带功率值较治疗前下降，双侧额、颞、顶、枕区θ频带功率值较治疗前均明显下降(P<0.05)。结论:盐酸美金刚对轻、中度AD有较明确的近期疗效,药物脑电图可作为指导AD患者诊疗的重要手段。

Abstract:目的:总结和分析我科收治的5例伴有恶性心包积液的晚期肺癌急诊入院患者采用心包内置管分次引流后注射顺铂和香菇多糖治疗的经过和预后，以探索此类疾病有效的治疗方法。方法:5例伴有恶性心包积液的晚期肺癌患者入院时均有心包填塞症状和体征且病情较重，其中1例处于全心衰竭、循环衰竭状态。入院后所有患者均及时接受心包置管分次引流后心包内注射顺铂和香菇多糖,并进行相应的后续治疗和随访。结果:5例患者经心包内置管引流和心包内药物注射后心包填塞症状和体征均有不同程度好转，获得完全缓解（CR）3例、部分缓解（PR）1例，进展（PD）1例。随访结果表明：5例患者均因癌症未能得以控制而进一步恶化死亡，其中3例死于肺癌所致气道阻塞、呼吸衰竭，另2例死于恶病质。心包积液获得CR的3例患者(曾继续接受多次不同方案的化疗)存活时间分别为10个月、18个月和19个月，而且有2例至死前再未见有心包积液症状、体征和影像学证据。结论:本组资料结果提示，对于伴有恶性心包积液的晚期肺癌，即使病情处于终末期，实施积极的治疗措施仍有可能控制病情，从而获得生活质量的提高和生存期延长。心包内置管分次引流后注射顺铂和香菇多糖则不失为一种有效的方法，值得进一步在更多的此类病例中验证。

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Abstract:目的:通过体外实验观察DNA甲基化转移酶抑制剂5-氮-2′脱氧胞苷(5-aza-2′deoxycytidine, 5-aza-dC)对人肺腺癌细胞增殖、凋亡及相关基因表达的影响，初步探讨其在治疗肺部肿瘤的作用及可能机制。方法：分别以0.5、2.0、10.0 μmol/L的5-aza-dC处理人肺腺癌A549细胞，用MTT法测定药物干预72 h后的光密度值，计算抑制率，流式细胞仪检测5-aza-dC对肺癌细胞株细胞周期及凋亡的影响，实时定量PCR检测相关基因p21、Cyclin D1、Bax和Bcl-2 mRNA的表达。结果：5-aza-dC能抑制人肺癌细胞株A549的增殖，且呈浓度依赖性； G0/G1期细胞比例下降，S期及G2/M期细胞比例明显高于对照组，出现G2/M细胞周期阻滞；同时，5-aza-dC能诱导A549细胞凋亡；与对照组比较，各药物干预组p21 mRNA表达升高(均P＜0.01)，而Cyclin D1 mRNA表达无明显变化(P＞0.05)；与对照组比较，各药物干预组Bax、Bcl-2 mRNA表达均明显降低(均P＜0.01)，且Bax/Bcl-2增高。结论：5-aza-dC能抑制肺癌细胞株的增殖、引起G2/M细胞周期阻滞，并促进凋亡，其机制可能与p21基因的上调及Bax/Bcl-2比值改变有关。

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