Objective To prepare a kind of P-selectin antibody loaded-targeted ultrasound contrast agent,and to investigate its ability of targeting in vitro.Methods P-selectin antibody loaded-targeted ultrasound contrast agent was prepared via an avidin-biotin bridge.Its basic property was determined.Human umbilical vein endothelial cells (HUVECs) were stimulated to express P-selectin by applying different doses of recombinant human interleukin-4 (rhIL-4) and histamine.The expression level of P-selectin was detected by immunofluorescence technique,and explored rhIL-4 optimal stimulation dose.The experiment group was divided into 3 groups,including targeted ultrasound contrast agent,isotype control ultrasound contrast agent and blank ultrasound contrast agent.Targeting abilities of 3 groups were observed by adhering to treated HUVECs and untreated HUVECs,respectively.Results P-selectin antibody loaded targeted ultrasound contrast agent was prepared successfully.The average diameter was (2.24 ± 0.71)μm.The average Zeta potential was (-2.75 ± 0.84)mV.The concentration was (3.0 ± 0.3) × 109/ml.The rate of antibody binding was as high as 99.80％.RhIL-4 and histamine could stimulate HUVECs to express P-selectin,and optimal stimulation dose was obtained.Targeting experiment showed that targeted ultrasound contrast agent could preferably adhere to HUVECs stimulated by optimal dose of rhIL-4 and histamine.Compared with other groups,there were significant differences.Conclusions P-selectin antibody loaded targeted ultrasound contrast agent was prepared successfully via an avidin-biotin bridge.The targeted ultrasound contrast agent could effectively adhere to HUVECs stimulated by rhIL-4 and histamine.

Compound traditional Chinese medicine database was established by collecting 176 compound formulas for dysmenorrhea in the last twenty years. The proportion and frequency of herbal medicine were analyzed and the main herbs with mono-target or multi-target in the compound formulas were selected with simple and multiple linear regression. The linear regression equations were listed and the clinical effects of the compound formulas were evaluated. Of 173 herbs used in the compound formulas, the proportion and frequency of the herbs for activating blood and transforming stasis and regulating qi flow were high in the application. The dosage interval for 20 herbs in common use was estimated. Main herbs with mono-target or multi-target used in the compound formulas were selected with simple and multiple linear regression. The total effectiveness rate of the 176 compound formulas was tested with simple linear regression, and 167 compound formulas (94.84 % of the total) had the absolute error less than 4%. Herbs for activating blood and transforming stasis and regulating qi flow are most commonly used in treatment of dysmenorrhea. Clinical effects of the compound formulas could be forecast with stepwise regression equation.

Objective To investigate the application value of real clinical case centered situation simulation examination model in clinical medicine. Methods Two classes were randomly selected from 2008 grade clinical medicine majors, respectively as test group(n=158) and control group(n=156). Final examination of test group includes usual performance, case-oriented situation simulation examination (COSSE) and final written examination. Traditional methods were used in control group. The same paper was used in final written examination of the two groups. Scores of written examination and question-naires were used to evaluate the COSSE model. Data were processed using SPSS 16.0 statistical software;t and chi-square tests were used to analyze the data;P<0.05 signifies that the difference is statistically sig-nificant. Results Scores of final examination in test group were higher than those in control group(P<0.001). Times of independent completion of history taking, physical examinations and medical record writing were more in test group than in control group(P=0.002,0.017,0.048). Conclusions Contents and methods of COSSE is conducive to improving student's professional comprehensive ability.

Objective To quantify the right ventricular (RV) function in patients with left heart disease (LHD) related pulmonary hypertension (PH) by two-dimensional speckle tracking imaging (2D-STI),and explore its potential value in diagnosis of reactive PH.Methods Forty healthy volunteers and 65 patients with LHD related PH were enrolled.PH patients were further divided into two subgroups according to pulmonary vascular resistance(PVR):passive PH group and reactive PH group.A complete 2D-STI derived longitudinal strain of RV free wall was performed,and the basal,middle,apical longitudinal peak systolic strain (LS) and RV free wall global LS (RVLSbas,RVLSmid,RVLSapi and RVLSfw) were measured.Results Compared to control group,RVLSbas and RVLSfw in reactive PH group decreased significantly (all P ＜0.05).Compared to passive PH group,RVLSbas and RVLSfw in patients with reactive PH decreased significantly (all P ＜0.05).The differences of RVLSbas and RVLSfw between control group and passive PH group had no statistical significance (all P ＞0.05).No significant differences in etiology and left ventricular ejection fraction (LVEF) were observed between PH subgroups (all P ＞0.05).The area under the ROC curve of RVLSbas in predicting reactive PH was 0.93,the cut-off value was-21.86,and the sensitivity and specificity were 83 ％ and 89 ％,respectively.The area under the ROC curve of RVLSfw was 0.79,the cut-off value was-13.84,and the sensitivity and specificity were 59％ and 89％,respectively.Conclusions 2D-STI can realize quantitative assessment of RV function in patients with LHD related PH.RVLSbas and RVLSfw may have important clinical value in diagnosing patients with reactive PH,and differential diagnosis value between patients with passive PH and patients with reactive PH.

Objective To investigate whether pulsed ultrasound-mediated microbubbles destruction could effectively enhance the efficiency of liposome delivery plasmid to hepatoma cells.Methods The cultured HepG2 cells were divided into six groups.The first group was as contrast group and the second group was given proper dose of liposome and plasmid.Pulsed-ultrasound exposed liposome was the third group.Add plasmid and microbubbles to the fourth group and exposed to pulsed-ultrasound.Add plasmid and liposome to the fifth group and exposed to pulsed-ultrasound,too.Liposome with plasmid and microbubbles were applied to the sixth group and exposed to ultrasound.After 24 hours,the EGFP expression in the hepatoma cells was detected by fluorescence microscopy and MTT.Results Green fluorescence intensity and transfection efficiency of the fifth group were higher than that of other groups,and cell viability had no significant difference.Although they were high in the sixth group,cells were partly died.Conclusions The liposome delivered EGFP expression efficiency in hepatoma cells was increased with the administration of pulsed ultrasound-mediated microbubbles destruction.In certain condition,microbubbles can enhance the efficiency of plasmid.

Objective To provide an comprehensive evaluation of the correlation between sleep apnea hypopnea syn?drome (SAHS) and nonalcoholic fatty liver disease (NAFLD). Methods The various case-control studies on the relation?ship between SAHS and NAFLD were retrieved from all kinds of large-scale databases at home and abroad (including Web of science, EMbase, Pubmed, Springer Link, EBSCO Databases, CNKI, CQVIP, Wanfang Data). The quality evaluation of in?cluded studies was made by two independent researchers. RevMan 5.1 and stata 12.0 software were used for meta-analysis. Results A total of 11 qualified documents were included in this study. Meta analysis showed that the relative risk of NAFLD was increased in SAHS patients than non-SAHS patients (RR=2.82, 95%CI:2.03-3.92, P<0.01). The serum ala?nine aminotransferase (ALT) increased in SAHS patients (SMD=0.53, 95% CI:0.02-1.05, P < 0.05). Compared with non-SAHS patients, the apnea-hypopnea index (AHI) was significantly higher in SAHS patients combined with severe NAFLD than those combined with mild NAFLD (SMD=1.42, 95%CI:0.12-2.72, P < 0.05). Conclusion The risk of NAFLD in?creases in SAHS patients. The severity of NAFLD is relatively higher with the severity of intermittent hypoxia.

Objective To evaluate the right ventricular global and regional strain and strain rate in patients with metabolic syndrome(MS) by two‐dimensional speckle tracking imaging(2D‐STI) ,and explore the correlation between different MS criteria and global strain and strain rate of right ventricle . Methods Forty‐four MS subjects ,35 pre‐MS subjects and 40 healthy subjects were enrolled . The basal ,middle and apical systolic longitudinal peak strain( Ss) and strain rate( SRs) ,early diastolic and late diastolic peak strain rate(SRe ,SRa) of right ventricular free wall were measured using 2D‐STI and global strain and strain rate ( GSs ,GSRs ) ,early diastolic and late diastolic peak strain rate ( GSRe ,GSRa ) of right ventricle were calculated . The correlation between different MS criteria and GS ,GSR of right ventricle were analyzed . Results Compared with control group ,Ss ,SRs ,SRe and SRa in basal and middle segments in MS group and Ss ,SRs in basal segment in Pre‐MS group decreased( all P < 0 .05) . Ss and SRs in basal segment in MS group were significantly lower than those in Pre‐MS group(all P <0 .05) . Compared with control group , GSs ,GSRs ,GSRe and GSRa in MS group and GSs ,GSRs in Pre‐MS group decreased ( all P <0 .05) . GS and GRS in MS group and Pre‐MS group had no statistical significance( all P > 0 .05) . There were good correlation of waist circumference(WC) ,systolic blood pressure(SBP) ,fasting blood‐glucose with GSs( r =-0 .73 ,-0 .69 ,-0 .46 , P < 0 .01) and GSRs( r = -0 .63 ,-0 .78 ,-0 .48 , P < 0 .01) . The multiple regression analysis of MS criteria showed that waist circumference and systolic blood pressure were independently associated with GSs and GSRs of right ventricle(β= -0 .44 ,-0 .77 , P <0 .01) . Conclusions 2D‐STI could accurately assess right ventricular global and regional function in MS patients .Among all MS risk factors ,waist circumference and systolic blood pressure are the most responsible for right ventricular function .

Objective To prepare the lipid ultrasound microbubbles carrying gene and transactivating transc"ptional activator(Tat)peptide and to study the efficiency of carrying gene and Tat as well as to study their ability as an ultrasound contrast agent.Methods The lipid ultrasound microbubbles were prepared using mechanical vibration method.The appearance,distribution,concentration,diameter and zeta potential were measured.The efficiencies of carrying gene and Tat were studyed by a confocal laser scanning microscopy and a fluorospectrophotometer.For the in vivo experiment,contrast-enhanced ultrasonography was performed on six rabbits to observe the duration and intensity of enhancement in the heart chambers and myocardium after the injection of the microbubbles.Results The diameter of the self-made lipid microbubbles carrying gene and Tat was(2.27±0.38)μm,the concentration was(3.07±0.42)×109/ml and zeta potential was(1.95±0.13)mV.The gene encapsulation efficiency for the lipid ultrasound microbubbles was 32%,and the Tat encapsulation efficiency was 35%.The in vivo experiment showed that the lipid ultrasound microbubbles could significantly enhance the echo intensity of myocardium.Conclusions The efficiency of carrying gene and Tat for the prepared lipid microbubbles is high,which can be used as a new vehicle carrying genes or drugs for therapy as well as an ultrasound contrast agent.

Objective To prepare a novel ultrasound contrast agent , targeted phase-shift lipid nanoparticles mediated by tumor homing and penetrating peptide tLyP-1 ,and to evaluate its characteristics . Methods The nanoparticles were prepared by filming-rehydration and acoustic-vibration methods .The morphology ,distribution ,particle size and zeta potential were detected . After heating and irradiating of low intensity focused ultrasound ( LIFU) ,the phase-shift characteristic and the enhancement effect in vitro were observed . The tumor homing and cell-penetrating properties of the nanoparticles were examined by confocal laser scanning microscopy and flow cytometry . The cytotoxicity of the nanoparticles was evaluated by CCK 8 assay . Results The size and distribution of nanoparticles were uniformed . The size and zeta potential of nanoparticles were ( 399 .50 ± 29 .98) nm and ( 3 .28 ± 1 .72) mV ,respectively . When the nanoparticles were heated to a temperature of 45 ℃ or after irradiated by LIFU ,nanoparticles generated phase-shift and enhanced ultrasound imaging in vitro ( P < 0 .05 ) . The confocal laser scanning microscopy showed that nanoparticles mediated by tLyP-1 can targetedly aggregate to cell membrane of MDA-MB-231 and penetrate into the cell ,but not to HUVEC . The flow cytometry showed that intracellular fluorescence intensity of nanoparticles mediated by tLyP-1 in MDA-MB-231 group was higher than that in control groups ( P <0 .05) . The CCK8 assay indicated that different concentrations of nanoparticles had no significant effects on cell activity ( P > 0 .05 ) . Conclusions A novel ultrasound contrast agent , targeted phase-shift lipid nanoparticles mediated by tumor homing and penetrating peptide tLyP-1 ,is prepared successfully . It can target to MDA-MB-231 cell and penetrate into the cell in vitro ,and enhance ultrasound imaging in vitro after LIFU irradiation ,which expected to become a novel tumor targeted ultrasound contrast agent and achieve ultrasound molecular imaging at the level of tumor cell .

Objective:To observe the efficacy and safety of mechanical ventilation combined with different doses of sildenafil in the treatment of persistent pulmonary hypertension of newborn (PPHN).Methods:A total of 160 children with PPHN admitted to Dezhou Maternal and Child Health Hospital from January 2018 to December 2019 were selected and divided into group A, B, C and D by random stratification, with 40 cases in each group. All the children in the group were actively corrected for acidosis, provided with intravenous nutrition support, warmth, anti-infection and other measures, and adopted ventilator to assist mechanical ventilation. Group A, B, and C were given different doses of sildenafil 0.5, 1.0, and 2.0 mg/(kg·time) respectively, while group D was not given sildenafil treatment, but only mechanical ventilation. Blood gas analysis indexes including partial arterial oxygenpressure (PaO 2), partial arterial carbon dioxide pressure (PaCO 2), saturationoxygen (SaO 2), and pulmonary artery pressure (SPAP), systemic blood pressure (SBP) of children were tested before the treatment and 72 h after the treatment. The treatment time, hospitalization time, hospitalization expenses and the incidence of adverse reactions of mechanical ventilation in 4 groups were recorded and compared. Results:The effective rate in the group A, B and C was higher than that in the group D: 80.0%(32/40), 85.0%(34/40), 87.5%(35/40) vs. 57.5%(23/40), the difference was statistically significant ( P<0.05). Before treatment, the levels of blood gas analysis indexes in 4 groups had no significant differences ( P>0.05). After treatment, the level of PaO 2 in the group A, B and C was significantly higher than that in the group D ( P<0.05), the level of PaCO 2 in the group B and C was significantly lower than that in group D ( P<0.05), and the level of SaO 2 in the group B and C was significantly higher than that in the group D ( P<0.05). After treatment, the level of SPAP in group B and C was significantly lower than that in the group D: (28.56 ± 3.93), (27.14 ± 3.32) mmHg(1 mmHg = 0.133 kPa) vs. (33.57 ± 4.68) mmHg, P<0.05, and the level of SBP in 4 groups had no significant difference ( P>0.05). The hospitalization time and mechanical ventilation time in group A, B and C were significantly shorter than those in group D ( P<0.05). No drug-related adverse reactions, pulmonary hemorrhage, hypotension, arrhythmia, pneumothorax and other complications occurred during the treatment in the 4 groups. Conclusions:Mechanical ventilation combined with sildenafil can significantly reduce pulmonary artery pressure and improve pulmonary oxygenation in children with PPHN. In the range of 0.5 - 1.0 mg/kg, the efficacy is more obvious when increasing the dose of sildenafil.