ABSTRACT
Objective:To investigate the correlation of blood pressure variability within 24 h after thrombolysis with symptomatic intracerebral hemorrhage (sICH) and 90 d outcome in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke treated with recombinant tissue plasminogen activator in the Department of Neurology, Jinshan Branch, Shanghai Sixth People's Hospital from January 2017 to May 2019 were enrolled prospectively. The baseline data of the patients were collected. The patients were divided into sICH group and non-sICH group according to the changes of head CT and the National Institutes of Health Stroke Scale (NIHSS) score after thrombolysis. At 90 d after thrombolysis, the modified Rankin scale was used to evaluate the outcomes, and the patients were divided into a good outcome group (0-2) and a poor outcome group (3-6). The blood pressure within 24 h after thrombolysis was monitored and the parameters related to blood pressure variability in 5 time periods (0-2 h, 2-6 h, 6-12 h, 12-18 h, and 18-24 h) were calculated, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) maximum (max), minimum (min), maximum and minimum difference (max-min) and mean (mean). The differences between the adjacent blood pressures were calculated, the standard deviation (SD), successive variation (SV), rise successive variability (SVrise), drop successive variability (SVdrop), the maximum squared difference in blood pressure rise (SVrisemax), the maximum squared difference in blood pressure drop (SVdropmax) were calculated and recorded, respectively. Multivariate logistic regression analysis was used to evaluate the effect of various blood pressure variability parameters on sICH and the outcomes after intravenous thrombolysis. Results:A total of 112 patients receiving intravenous thrombolysis were included in the study. Their median age was 71 years (range, 38-92 years), 66 were males (58.9%); median baseline NIHSS score was 10. Seventeen patients (15.2%) developed hemorrhagic transformation, 10 of them (8.9%) were sICH. The 90-d follow-up showed that 73 patients (65.2%) had a good outcome, 39 (34.8%) had a poor outcome and 7 of them (6.3%) died. There were significant differences in hypertension ( P=0.029), ischemic heart disease ( P=0.012), total cholesterol ( P=0.033), baseline NIHSS score ( P=0.003) between the sICH group and the non-sICH group. There were significant differences in age ( P=0.025), gender ( P=0.005), atrial fibrillation ( P=0.003), etiologic classification of stroke ( P=0.003), baseline NIHSS score ( P<0.001) and sICH ( P=0.003) between the poor outcome group and the good outcome group. In addition, there were significant differences in multiple blood pressure variability parameters among the above groups (all P<0.05). Multivariate logistic regression analysis showed that DBP SVdropmax, 6-12 h DBP SV, 12-18 h DBP SV, 6-12 h DBP SVdrop, 12-18 h DBP SVdrop were the independent risk factors for sICH after intravenous thrombolysis (all P<0.05); 2-6 h SBP SV, 2-6 h SBP SVrise, 2-6 h SBP SVdrop, 2-6 h DBP SV, 2-6 h DBP SVrise and 2-6 h DBP SVdrop were the independent risk factors for poor outcome after intravenous thrombolysis (all P<0.05). Conclusions:Early blood pressure and some blood pressure variability parameters are closely related to sICH and outcomes after intravenous thrombolysis in acute ischemic stroke. Closely monitoring of blood pressure and its variability can help clinical management and outcome prediction after intravenous thrombolysis.
ABSTRACT
@#In this study, normal isolated rat heart model was adopted to investigate the inotropic and electrocardiac effect of AF-HF001 with Lanfendorff technique on the left ventricular systolic pressure(LVSP), left ventricular end diastolic pressure(LVEDP), peak rate of rise of left ventricular pressure(+dp/dtmax)and peak rate of fall of left ventricular pressure(-dp/dtmax). The results indicated that AF-HF001 could significantly enhance LVSP, LVEDP and ±dp/dtmax in a dose-dependent manner and exerted a positive inotropic effect on normal isolated rat hearts. This study also analyzed the electrocardiac effect of AF-HF001 with the electrodes located on tip of heart, ventricular free wall and aortic root. The results exhibited that AF-HF001 did not change PR, QRS, QT or HR at various concentrations, which means that AF-HF001 could safely increase cardiac contractility. This research lays a good foundation for the further study on AF-HF001 and research on structure-activity relationship of its analogs.
ABSTRACT
@#Glucokinase(GK), which plays a pivotal role in maintaining glucose equilibrium in the human body, emerged as one of the most promising targets for the treatment of diabetes mellitus type 2. Pharmacophore models of glucokinase agonist inhibitors have been generated with a training set of 25 glucokinase agonists(EC50 values from 2 to 78 000 nmol/L)using Discovery studio 2. 5. The best hypothesis contained three hydrogen bond acceptors, one hydrophobic center, and three excluded volumes with a correlation coefficient of 0. 955, cost difference of 60. 5, RMSD of 0. 714. This model was validated by test set, Fischer randomization test and decoy set methods. Pharmacophore model was also utilized as a three dimentional query to screen in-house andrographolide derivative database. New potential GK agonist was obtained therewith, and the hit compound is capable for further screening assay studies. Preliminary biological evaluation suggests that this new pharmacophore model fuctions superiorly in virtual screening.
ABSTRACT
BACKGROUND: The rudiment of tissue engineering is to obtain tissue from patients. The cells are expanded into a population through cellular culture, and seeded into scaffolds, which can accommodate and guide the growth and proliferation of new cells in the three-dimensional scaffolds. At last, the constructed tissue is transplanted in vivo to repair or replace damaged or diseased tissues. Afterward neovascularization of the graft, the scaffolds are absorbed gradually. Finally, the new tissue replaces completely the damaged or diseased tissuesOBJECTIVE: To evaluate the feasibility of designing and fabricating customized anatomical-shaped bone tissue-engineering scaffolds with reverse engineering and rapid prototyping (RP) techniques. To avoid the disadvantage of the conventional fabricated methods of the scaffolds.DESIGN: The method of fabricating customized anatomical-shaped bone tissue engineering scaffolds.SETTING: Computer-aided design (CAD) of the scaffold was conducted in CAD training center, Guangdong Machinery Research Institute. Rapid prototyping fabrication of the scaffold was conducted in Guangdong Longchuangyu Limited Cooperation. The scaffold was fabricated by sterophotocureable technology and was made of photosensitized resin.METHODS: This experiment was carried out at the Center of Department of Traumatic Orthopedics, General Hospital of Guangzhou Military Area Command of Chinese PLA from October 2004 and January 2005. According to reverse engineering, layered image information of skeleton of the patients was scanned with CT/MRI. Anatomical models of region of interesting were created by means of CT or MRI three-dimensional reconstruction and surface reconstruction. The internal construction of the scaffolds was designed with CAD software in the outline of the anatomical models to develop computer-aided model. The prototypes of the scaffolds were fabricated by RP process.MAIN OUTCOME MEASURES: ①CT/MRI scanning, three-dimensional reconstruction, anatomical modeling; ② computer-aided design of customized bone tissue engineering scaffolds; ③rapid prototyping fabrication of customized bone tissue engineering scaffold.RESULTS: ①Anatomical models of bone joint were established through CT/MRI three-dimensional reconstruction. ② The internal structure of the scaffold was designed to establish the entity model of bone tissue engineering scaffold successfully with computer-aided design software. ③ CAD model of bone tissue engineering scaffold guided prototypes to develop the customized anatomical-shaped bone tissue engineering scaffolds. The internal structure of bone tissue engineering scaffold was fine and had high degree of porosity-and pore interconnectivity.CONCLUSION: Customized anatomical-shaped bone tissue engineering scaffolds can be fabricated with reverse engineering and RP technology. Among all RP processes, stereophotocureable technology (SLA) is the best one with good precision, smooth surface and good shaping.