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Objective:To investigate and evaluate the safety of intravitreal injection of recombinant human endostatin (rh-endostatin) with different concentrations in rabbit eyes.Methods:Thirty healthy adult New Zealand white rabbits were enrolled with the right eyes selected as experimental eyes, and were randomly divided into five groups by random distribution of computer numbers, with 6 eyes in each group.The rabbits in the normal control group were given no treatment, and the rabbits in the normal saline group, 0.125 mg rh-endostatin group, 0.250 mg rh-endostatin group and 0.500 mg rh-endostatin group were treated with 100 μl of normal saline, 0.125 mg/100 μl, 0.250 mg/100 μl and 0.500 mg/100 μl rh-endostatin according to grouping, respectively.The anterior segment and fundus of the experimental eyes were examined using slit lamp biomicroscope and indirect ophthalmoscope, and the intraocular pressure (IOP) of the experimental eyes were measured with iCARE handheld tonometer before injection and 1 day, 3, 7, 14, 30 and 60 days after injection.Optical coherence tomography (OCT) examination was performed before the intravitreal injection and 7, 30, and 60 days after injection, respectively.Flash electroretinogram was performed before intravitreal injection and 14 days and 60 days after injection.The rabbits were sacrificed by euthanasia at 60th day after injection.Three experimental eyes of each group were dissected and made into paraffin section, and histopathological staining was used to detect the retinal structural changes.The retinal tissue was separated from the other three study eyes in each group, and the transmission electron microscope was employed to observe the ultrastructural changes of the retina.All animal experiments were performed in adherence to the Regulations of the State and the Animal Center of Yangzhou University Medical College for the Use of Animals in Research.Results:After intravitreal injection, no obvious anterior or posterior chamber change was observed by slit lamp microscopy in all groups at any time point.Flocculent seepage was observed in one eye of the 0.125 mg and 0.500 mg rh-endostatin group, respectively, which was then absorbed completely on the 7th and 14th day.OCT examination showed no abnormal light reflection or morphological changes in fundus of day after injection in all the groups.There was no significant difference in IOP, a-wave and b-wave amplitude among all the groups at different time points ( Fgroup=0.134, 0.101, 0.476; Ftime=1.709, 2.479, 1.706; all at P>0.05). Neither light nor electron microscopy showed any retinal damage in any group. Conclusions:Intravitreal injection of rh-endostatin is safe at the dosage of 0.125-0.500 mg in rabbits.
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Objective To discuss the efficacy and safety of urapidil combined with fructose injection in hypertensive elderly patients with acute heart failure(AHF).Methods Sixty-two elderly patients with acute heart failure complicated with hypertension from cardiovascular medicine of the fifth people's hospital of qinghai province were randomized into urapidil group (n =30)and urapidil combined with fructose treatment group (combined group,n =32).Two groups of patients were given regular heart failure treatment (oxygen,strong heart,diuresis,ACEI,etc),patients in urapidil group were treated with urapidil 50-100μg/min,48 h after continuous dosing,individualized adjust delivery time,dosing time adjustmented as individualized.On the basis of urapidil group,patients in combined group were treated with Fruc-tose-1,6-Diphosphate (FDP) injection of 5.0g,intravenous drip within 10 minutes,the duration was 7 days in two groups.The clinical efficacy was compared in two groups after treatment.Their parameters were compared before and on days 1,2,3 and 7 after treatment.The adverse reactions occur were recorded in patients of two groups during the treatment.Results There was no statistically significant difference in baseline data such as sex ratio,age,etc between the two groups (P ＞ 0.05).The total clinical efficacy rate in combined group was significantly higher than urapidil group(87.50％ vs 73.33％,x2 =6.102,P =0.047).The systolic pressure,diastolic blood pressure and heart rate of each time after treatment were gradually lower than before treatment in the two groups patients.These was no statistical significance difference in blood pressure and heart rate between the two groups at each time point after treatment (P ＞ 0.05).Compared with urapidil group,the left entricular ejection fraction (LVEF) and cardiac index (CI) were rised significantly.The left ventricular end systolic diameter (LVESD) and left ventricular end systolic volume (LVESV) were significantly decreased.The plasma N-terminal brain natriuretic peptide (NT-proBNP) was significantly reduced (P ＜ 0.05) in combined treatment group patients after treatment 7 days.There was no reflectively heart rateaccelerating in combined treatment group.Urapidil combined with fructose showed no bad influence on blood glucose,cholesterol and triglyceride.And combined treatment groups patients had significantly less side effects than their counterparts in urapidil group,but had no obvious statistical significance difference (10.00％ vs 3.13％,x2 =1.213,P =0.321).Conclusion Urapidil combined with fructose injection treatment hypertensive elderly patients with acute left heart failure demonstrated better efficacy and less side effects than urapidil alone on lowering and stabilizing systolic BP,improving cardiac function more significant.
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Objective To develop a method for determination of the plasma protein binding rate of bisoprolol in human plasma by high performance liquid chromatography ( HPLC) combined with hollow fiber-based liquid-phase microextraction ( HF-LPME) . Methods Method of liquid phase microextraction was optimized. The concentration of bisoprolol in the reconstitute solution was analyzed by HPLC. The mobile phase consisted of water-methanol-acetonitrile-0. 1% phosphoric acid (50:34:6:10). The excitation wavelength was 232 nm and emission wavelength was 300 nm. Through the linear regression equations, the total and free concentrations were obtained, and then the protein binding rate was calculated. Results At low, middle, and high concentration, the protein binding rate of bisoprolol was 31. 2%, 32. 0% and 31. 8%, respectively. Conclusion The proposed method is proven to be simple, fast and reproducible, and is feasible for the determination of plasma protein binding rate of bisoprolol. Bisoprolol moderately binds with plasma protein independent of concentration.
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Objective To explore the impact of lung-protective mechanical ventilation (low tidal volume and optimal positive end-expiratory pressure (PEEP) on cerebral perfusion pressure (CPP) and cerebral oxygen metabolism.Methods Forty patients with severe cerebral injury along with respiratory failure were randomly assigned into two groups:lung-protective ventilation group A and conventional ventilation group B.Group A was planned to prescribe tidal volume 6 ～ 8 mL/kg,initial FiO240％,PEEP gradually increasing from 2 cmH2O to matched with FiO2 elevation,but the FiO2 was kept at permissive lower level.Group B was formulated with tidal volume 8 ～ 12 mL/kg,PEEP stepwise increasing from 0 2 cmH2O to match with FiO2 elevation,but PEEP was kept at permissive lower pressure.The intracranial pressure (ICP),mean arterial pressure (MAP),CPP,arterial and jugular venous blood gas were monitored.Results PEEP (8.2±3.32 cmH2O),ICP (19.7 ±3.6 mmHg),PaCO2 (54±7.3 mmHg),jugular venous carbon dioxide partial pressure (PjV CO2,56.7 ± 9.6 mmHg) in group A were higher than those (5.7±2.3 cmH2O,16.9±3.8 mmHg,41 ±5.2 mmHg,49.8 ±6.9 mmHg) in group B (P＜ 0.05 or P ＜ 0.01).VT,FiO2 in the group A were lower than those in the group B.There were no differences in PaO2/FiO2,jugular venous oxygen saturation (SjVO2),MAP,and CPP between two groups.PaCO2 were significantly correlated with CPP (r =0.368,P =0.019) while there was no correlation with ICP,PaO2,SjVO2,PjVCO2 (all P ＞0.05).CPP (69.7 ± 12.3 mmHg) was higher in case of PaCO2 (46 ～60mmHg) than those (61.5 ±9.1 mmHg) in case of PaCO2 (35 ～45 mmHg).There was correlation between PEEP and ICP (r =0.436,P =0.005).When PEEP was divided into three groups:≤52 cmH2O,6 ～ 102 cmH2O and ＞ 102 cmH2O,ICPs were different one another among three groups.When PEEP ＞ 102 cmH2O,it had a distinguished negative correlation with CPP (r =-0.395,P =0.017),while PEEP ≤ 102 cmH2O,CPP presented decreasing tendency.SjVO2 correlated with PaO2 (r =0.403,P =0.014) and PjVCO2 (r =-0.502,P =0.001) respectively.There were no significant relationships between SjVO2 and CPP,ICP,MAP,PEEP,respectively.Conclusions Lung-protective mechanical ventilation was relatively safer in patients with severe cerebral injury compared with conventional mechanical ventilation.Mild PaCO2 elevation (46 ～ 60 mmHg) combined with higher PEEP (＜ 102 cmH2O) did not decrease CPP.There was no difference in SjVO2 between the two modes of mechanical ventilation,suggesting no changes in cerebral metabolism occurred.
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Objective To investigate Fascin expression in human lung cancer tissues and its clinical significance.Methods Immunohistochemistry was performed in 62 patients with different histological types and clinical stages of lung cancer and 92 cases with other malignant tumors.Fascin positive rate in each group was calculated and the differences of pathological characters between the two groups were analyzed.Results Fascin expression in lung cancer tissues was significantly higher than that in normal lung tissues(P ＜ 0.05),its expression varied by different clinical stage of lung cancer tissue differentiation.As differentiation degree decreased,Fascin positive rate increased.Fascin expression was independent with age,sex,smoking history(P ＞ 0.05).Fascin expression had no significant difference between lung cancer group and other tumor group(P ＞ 0.05).Conclusions Fascin expression raising might be common in malignant tumors.Fascin expression in lung tissues indicated the possibility of lung cancer.In lung tissue,high expression of Fasein was a sign of poor differentiation and malignant status of lung cancer.
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Objective To investigate the values of ultrasound measuring of the placenta thickness on evaluation of risks for alpha-thalassemia at the early pregnancy.Methods Two-dimensional ultrasound was performed to measure the thickness of placenta on 208 cases of fetuses with alpha-thalassemia and 52 cases of normal fetuses in control group.The placenta thickness was expressed as multiples of the median(MOM).Results At the early pregnancy,the group of fetuses with alpha-thalassemia had significantly higher placenta thickness compared to the fetuses without alpha-thalassemia(P＜0.001).However,there were no statistical significant difference in the placenta thickness between the other groups(P=0.100).Placenta thickness 1.18 MOM was the best critical point to predict alpha-thalassemia.The sensitivity and specificity of placenta thickness >1.18 MOM in prediction of alpha-thalassemia was 82.9%,84.7% respectively.Conclusions For those with high risks of alpha-thalassemia placenta thickness measuring is a safe,effective parameter for assessment because it could reduce unnecessary invasive procedures and improve the detecting rate of severe alpha-thalassemia.
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Objective To investigate the thyroid hormone changes and their relationship with the state of severity in critically ill patients. Methods Ninety-two patients with no thyroidal illness syndrome admitted to the ICU from January ,2009 to December,2009 were enrolled in this study. The common situations and the score of acute physiology and chronic health evaluation Ⅱ were assessed on addmission. We measured the thyroid hormone levels on the day after admission and analysed whether thyroid hormone levels were related to disease severity. Results The thyroid hormone levels in septic shock group [TT3 (1.16 ± 0.24) nmol/L, TT4 (68.93 ± 24.11) nmol/L, FT3 (3.76 ± 0.21) prnol/L, FT4 (16.40 ± 2.74) pmol/L, TSH (1.58 ± 1.01) mU/L] were significantly lower than those in non-septic shock [TT3 (1.50 ± 0.25) nmol/L, TT4 (91.70 ± 21.90) nmol/L, FT3 (4.24 ± 0.45) pmol/L, FT4(17.98 ± 3.28) pmol/L, TSH (2.43 ± 2.76) mU/L] (P ＜ 0.05). The serum thyroid hormone levels of free triiodothyronine (FT3) ,free thyroxine (FT4) were related to the score of APACHE Ⅱ in septic shock(P ＜ 0.05).Conclusions The levels of thyroid hormone were significantly lower in critically ill patients than the control group and had positive correlation with the disease severity.
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Objective To investigate the reversal effects of tetramethylpyrazine(TMP) and cyclosporin A(CsA) on multidrug resistance(MDR) of human erythroleukemia cells with gene transfer K562/MDR and to discuss the possible correlative mechanism.Methods K562/MDR cells in culture medium were treated with TMP(50—6 400 mg?L-1) and CsA(0.5—256 mg?L1) respectively.The growth rates of these cells were measured by MTT assay.Non-cytotoxic doses of TMP and CsA were determined.There were 5 growps in the experiment:G1(TMP+ADM+K562/MDR),G2(CsA+ADM+K562/MDR),G3(TMP+CsA+ADM+K562/MDR),negative control(K562/MDR subsitituted by K562/S),control(drugs subsitituted by 1640 culture medium),the inhibitory effects of adriamycin(ADM) used alone or in combination with TMP or/and CsA on the proliferation of K562/S and K562/MDR cells were observed by resisting fold and reversal folds.The effects of TMP and CsA on ADM accumulation in K562/S and K562/MDR cells were analyzed by fluorospectrophotometry.The protein level of P-glycoprotein(P-gp) was detected by flow cytometry(FCM).Results The non-cytotoxic doses of TMP and CsA were 320 and 2.0 mg?L-1,respectively.The resistance of K562/MDR cells to ADM was 19.2 folds of that of K562/S cells.When TMP and CsA were added along with ADM to the K562/MDR culture,the reversal folds were 5.2 and 9.6.When TMP in combination with CsA was added along with ADM to the K562/MDR culture,the reversal folds were 15.6.When various concentrations ADM were added to the K562/MDR culture,TMP and CsA could increase the intracellular accumulation of ADM.The effect of TMP in combination with CsA was more evident.Compared with control,TMP and CsA could inhibit the overexpression of P-gp protein(P
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Objective To study effect of immediate abundant sucralfate suspension perfusion to prevent upper gastrointestinal hemorrhage on the organophosphorous insecticides toxicosis suffer after washing stomach.Methods Total 83 patients suffering organophosphorous insecticides toxicosis were divided randomly into 2 groups randomly.In the control group,40 samples were given cimetidine 0.4 g by vein injection after stomach washing completely twice one day. Meanwhile,they were taken sucralfate 1.0 g/(4 times day) orally or by nastal feeding,continuing 5 days.In the treatment group,the samples were perfused sucralfate suspension 3.0 g (grind to powder,mixed with warm water 80 ml) by stomach tube after each stomach washing,and given routine treatment to assist (method as the control group).Results In the aspects of recessive hemorrhage,conspicuous hemorrhage and hospitalizing period the treatment group was significant decreased compared with the control group (P＜0.05).However,Analysis of the results showed no significant difference in death rate (P＞0.05).Conclusion Immediate abundant sucralfate suspension perfusion after washing stomach has significant curative effect on preventing upper gastrointestinal hemorrhage and decreasing hospitalizing period.
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OBJECTIVE:To study the in vitro and in vivo metabolism of DX by intestinal bacteria in rats and volunteers and the active components in serum of rat after oral administration of DX 900mg/kg METHODS:To detect DX and its metabolites in stool,urine and serum with TLC and EST-MS RESULTS:In vitro,DX was decomposed easily by rat and human intestinal bacteria,and various metabolites were found With prolongation of metablism,metabolite with molecular weight of 415 3 was shown to be corresponding to diosgenin in rat serum and in urine of rats and volunteers CONCLUSION:The above-mentioned DX was decomposed easily by intestinal bacterias and diosgenin was absorbed into serum after oral administration of DX