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Objective:To explore the changes of right ventricular myocardial perfusion in pulmonary arterial hypertension (PAH) pig models with a quantitative analysis technique based on dynamic SPECT myocardial perfusion imaging, and analyze the relationship between myocardial blood flow, hemodynamics and right ventricular function.Methods:Eleven Chinese miniature pigs (all males, 6-8 months old) weighing 25-30 kg were selected. The PAH models were established by ligating the main pulmonary artery and embolizing the right lower pulmonary artery. After the models were established, dynamic myocardial perfusion imaging with one-day resting/adenosine stress 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT was performed, and the quantitative parameters of left and right ventricles were obtained, including stress myocardial blood flow (SMBF), rest myocardial blood flow (RMBF) and myocardial flow reserve (MFR: the ratio of stress to rest myocardial blood flow). Right heart catheterization was performed to evaluate the mean pulmonary arterial pressure (mPAP), and the right heart function index tricuspid annular plane systolic excursion (TAPSE) was measured by transthoracic echocardiography. According to TAPSE, animals were divided into right heart function preserved group ( n=5, TAPSE≥17 mm) and right heart dysfunction group ( n=4, TAPSE<17 mm). Pearson correlation analysis and the independent-sample t test were used for data analysis. Results:Nine experimental pig models were established with increased mPAP of (38.1 ± 11.6 ) mmHg (1 mmHg=0.133 kPa). Myocardial perfusion imaging showed clear radiotracer uptake in the right heart and myocardial hypertrophy. There was a significant positive correlation between right ventricular myocardial RMBF ((0.71±0.13) ml·min -1·g -1) and mPAP ( r=0.94, P< 0.001). The SMBF in the decreased right ventricular function group was significantly lower than that in the preserved right ventricular function group ((1.66±0.35) vs (2.24±0.30) ml·min -1·g -1;t=2.68, P=0.032). Conclusion:SPECT myocardial blood flow quantification can be used to evaluate the right ventricular myocardial blood flow in pig models of PAH.
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Objective:To investigate differences in cardiac function and perfusion parameters measured by IQ-SPECT and low energy high-resolution (LEHR)-SPECT, as well as effects of scattering correction (SC) and CT attenuation correction (AC) on myocardial perfusion imaging.Methods:From May 2020 to September 2020, 80 patients (58 males, 22 females, age (57±10) years) who underwent SPECT myocardial perfusion imaging were retrospectively enrolled in Fuwai Hospital. According to the standardized left ventricular end-diastolic diameter of body surface measured by two-dimensional echocardiography, patients were divided into 2 groups: A group ( n=34) with significantly enlarged left ventricle and B group ( n=46) with no significant enlargement of left ventricle. LEHR-SPECT and IQ-SPECT gated myocardial perfusion imaging were performed in all patients. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), summed rest score (SRS) and total perfusion defect (TPD) were measured. Parameters measured by two methods and differences before and after SC and AC were compared by using paired t test and Wilcoxon signed rank test. The correlation was analyzed by Pearson correlation or Spearman rank correlation analyses, and the consistency was analyzed by Bland-Altman analysis. Results:In A group, EDV, EF and SRS measured by IQ-SPECT were significantly lower than those assessed by LEHR-SPECT after SC and AC (EDV: (257±137) vs (276±154) ml, EF: (21±11)% vs (26±13)%, SRS: 17(6, 25) vs 18(8, 28); t values: -2.63, -7.46, z=-2.14, all P<0.05); all parameters measured by LEHR-SPECT and IQ-SPECT had well correlation ( r values: 0.965, 0.969, 0.967, rs values: 0.920, 0.960, all P<0.001) and consistency. In B group, EDV and EF measured by IQ-SPECT were significantly lower than those assessed by LEHR-SPECT after SC and AC (EDV: (96±40) vs (107±39) ml, EF: (46±15)% vs (54±16)%; t values: -6.23, -10.71, both P=0.001); SRS and TPD measured by IQ-SPECT after SC and AC were significantly lower than non-SC and non-AC (SRS: 2(1, 4) vs 5(3, 11), TPD: (3%(1%, 5%) vs 7%(3%, 12%); z values: -4.11, -4.16, both P<0.001); all parameters measured by LEHR-SPECT and IQ-SPECT had well correlation ( r values: 0.956, 0.978, 0.958, rs values: 0.926, 0.944, all P<0.001) and consistency. Conclusions:There are good correlation and consistency of left ventricular function and myocardial perfusion parameters acquired by IQ-SPECT and LEHR-SPECT. Moreover, IQ-SPECT is able to shorten acquisition time, resulting in great potential in clinical application.
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Objective:To study the feasibility of cardiac 99Tc m-methoxyisobutylisonitrile (MIBI)/ 123I-metaiodobenzylguanidine (MIBG) dual-isotope imaging with cadmium-zinc-telluride (CZT) SPECT. Methods:Using a heart phantom, 99Tc m-MIBI single-isotope imaging and 99Tc m-MIBI/ 123I-MIBG dual-isotope imaging were acquired separately. Model A, B, C represented normal heart, 99Tc m/ 123I matched myocardium, 99Tc m/ 123I mismatched myocardium, respectively. Nineteen patients (9 males, 10 females; age (56±16) years) from September 2018 to June 2020 at Fuwai Hospital were enrolled to participate 99Tc m-MIBI myocardial perfusion imaging and myocardial perfusion/cardiac sympathetic imaging with 99Tc m-MIBI/ 123I-MIBG dual-isotope. Perfusion percent (PP%) and summed rest score (SRS) for all myocardial segments were obtained using quantitative perfusion SPECT (QPS) software by analyzing myocardial perfusion images. Difference and relationship between PP% and SRS were analyzed (Pearson and Spearman correlation analyses). No physical correction was applied for both acquisitions. Analysis of variance for repeated measurement data and Mann-Whitney U test were used. Results:There was no significant difference in myocardial perfusion images between 99Tc m single-isotope and 99Tc m/ 123I dual-isotope imaging with the heart phantom. 123I did not significantly impact on 99Tc m images. For patients, PP% did not differ between 99Tc m single-isotope ((69.2±14.5)%) and 99Tc m/ 123I dual-isotope imaging ((69.5±16.2)%; F=0.005, P=0.946) and correlated well ( r=0.845, P<0.01). SRS for 99Tc m single-isotope was 2(1, 13) and 2(2, 12) for 99Tc m/ 123I dual-isotope imaging ( z=-0.774, P=0.439) and the correlation between the two acquisitions was excellent ( rs=0.975, P<0.01). Conclusions:Even without physical correction, cardiac images interpretation won′t be significantly influenced by the interference of 123I with relatively higher energy on 99Tc m images. Cardiac 99Tc m-MIBI/ 123I-MIBG dual-isotope imaging is feasible.
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Objective@#To investigate the biodistribution of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[2-18F-fluroethoxy]ethoxymethyl]-1H-1, 2, 3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone (18F-MyoZone) and evaluate its clinical potential as a PET myocardial perfusion imaging (MPI) tracer in mini-swine.@*Methods@#18F-MyoZone was prepared. Twelve Bama mini-swine were intravenously injected with approximately 111 MBq of 18F-MyoZone to evaluate PET imaging characteristics. Whole-body PET scans were performed at the timing of 5, 20, 40, 60 and 120 min postinjection to measure time-dependent mean standardized uptake value (SUVmean) in multiple organs of health animals (n=6). SUVmean ratios of myocardium/liver and myocardium/lung over time were then calculated. Mini-swine with induced acute myocardial infarction (n=3) and chronic myocardial ischemia (n=3) accompanying with health mini-swine (n=3) were utilized to evaluate the diagnostic capability of 18F-MyoZone PET MPI.@*Results@#The typical decay-corrected radiochemical yield of 18F-MyoZone reached (52.0±4.3)%(n=3) with a high radiochemical purity (>98%). In the biodistribution study, high initial myocardial uptake (SUVmean=10.40±2.40 at 5 min postinjection) and remarkable myocardial retention (SUVmean=9.30±2.00 at 120 min postinjection) were observed. The adjacent organs (like the liver and lungs) indicated low tracer uptake and rapid clearance. The heart/liver and heart/lung SUVmean ratios were 4.77±0.91 and 17.14±5.84 respectively at 5 min postinjection, with an increase to 11.16±1.38 and 21.69±7.09 at 120 min postinjection. In the MPI study of mini-swine, normal myocardium demonstrated uniform tracer distribution with clearly visualizable myocardial boundary, infarct myocardium and severe ischemia myocardium performed intense resting perfusion defect, and ischemia myocardium revealed reversible perfusion defect by stress/rest MPI. The myocardial image quality remained stable within 120 min postinjection.@*Conclusions@#MPI with 18F-MyoZone exhibits high initial myocardial uptake and low extracardiac activities in adjacent organs. Advantages in early imaging and wide diagnostic time window make it a promising PET MPI tracer.
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Objective@#To assess the superiority of 99Tcm-3SPboroxime (99Tcm-3SP for short) as a fast-myocardial perfusion imaging (MPI) tracer in normal and acute myocardial infarction (AMI) mini-swine.@*Methods@#99Tcm-3SP and 99Tcm-Teboroxime (99Tcm-TEBO for short) were prepared. Approximately 370 MBq 99Tcm-3SP or 99Tcm-TEBO was injected intravenously in 2 healthy mini-swine separately. Dynamic planar images were acquired immediately after injection and continued for 20 min using a standard SPECT camera. The radioactivity uptakes in the heart, liver, and lungs were measured, and heart/liver and heart/lung ratios over time were calculated. Dynamic SPECT studies were performed in 4 normal swine and 1 AMI-swine using cadmium zinc telluride-SPECT (CZT-SPECT). List mode acquisitions were immediately started and continued for 15 min after intravenous injection of approximately 370 MBq 99Tcm-TEBO and 99Tcm-3SP. The injection of two radiotracers in the same swine was completed within 2 d. The radioactivity uptakes in heart and liver were measured, and heart/liver ratio was calculated. Image quality was also evaluated. Paired t test was used to analyze the data.@*Results@#The radiochemical purity of 99Tcm-TEBO or 99Tcm-3SP were both above 95%. The initial heart uptake of 99Tcm-3SP was very close to that of 99Tcm-TEBO (planar image, 2 min postinjection: 309.32×103 vs 314.13×103 counts/MBq; SPECT image, 2 min postinjection (corrected): 7.96±0.87 vs 8.24±1.53, t=0.277, P>0.05), but the myocardial retention time was much longer than that of 99Tcm-TEBO (planar image, 20 min postinjection: 218.67×103 vs 143.19×103 counts/MBq; SPECT image, 15 min postinjection (corrected): 6.76±0.45 vs 5.06±0.33, t=-12.412, P=0.001). The uptake of liver and heart/liver ratio between 99Tcm-TEBO and 99Tcm-3SP were similar (t values: -1.332-1.101, all P>0.05 within 15 min). SPECT MPI images demonstrated uniform tracer distribution with clearly visualizable myocardial boundary in normal myocardium and intense perfusion defect in infarct myocardium. High quality SPECT images could be obtained in any of the 5 min imaging windows over the first 15 min after injection of 99Tcm-3SP in normal swine and AMI-swine.@*Conclusion@#99Tcm-3SP is a promising 99Tcm-labeled radiotracer for fast-MPI considering its high heart uptake, long myocardial retention time (20 min postinjection) and superior SPECT image quality.
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Objective To investigate the biodistribution of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[2-18 F-fluroethoxy] ethoxymethyl]-1H-1,2,3-triazol-4-yl] methyl] phenylmethoxy]-3(2H)-pyridazinone (18F-MyoZone) and evaluate its clinical potential as a PET myocardial perfusion imaging (MPI) tracer in miniswine.Methods 18F-MyoZone was prepared.Twelve Bama mini-swine were intravenously injected with approximately 111 MBq of 18F-MyoZone to evaluate PET imaging characteristics.Whole-body PET scans were performed at the timing of 5,20,40,60 and 120 min postinjection to measure time-dependent mean stand-ardized uptake value (SUVmean) in multiple organs of health animals (n =6).SUVmean ratios of myocardium/liver and myocardium/lung over time were then calculated.Mini-swine with induced acute myocardial infarction (n =3) and chronic myocardial ischemia (n =3) accompanying with health mini-swine (n =3) were utilized to evaluate the diagnostic capability of 18F-MyoZone PET MPI.Results The typical decay-corrected radiochemical yield of 18 F-MyoZone reached (52.0±4.3)％ (n =3) with a high radiochemical purity (＞98％).In the biodistribution study,high initial myocardial uptake (SUVmean =10.40±2.40 at 5 min postinjection) and remarkable myocardial retention (SUVmean =9.30±2.00 at 120 min postinjection) were observed.The adjacent organs (like the liver and lungs) indicated low tracer uptake and rapid clearance.The heart/liver and heart/lung SUVmean ratios were 4.77±0.91 and 17.14±5.84 respectively at 5 min postinjection,with an increase to 11.16± 1.38 and 21.69±7.09 at 120 min postinjection.In the MPI study of miniswine,normal myocardium demonstrated uniform tracer distribution with clearly visualizable myocardial boundary,infarct myocardium and severe ischemia myocardium performed intense resting perfusion defect,and ischemia myocardium revealed reversible perfusion defect by stress/rest MPI.The myocardial image quality remained stable within 120 min postinjection.Conclusions MPI with 18F-MyoZone exhibits high initial myocardial uptake and low extracardiac activities in adjacent organs.Advantages in early imaging and wide diagnostic time window make it a promising PET MPI tracer.
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Objective To assess the superiority of 99Tcm-3SPboroxime (99Tcm-3SP for short) as a fast-myocardial perfusion imaging (MPI) tracer in normal and acute myocardial infarction (AMI) mini-swine.Methods 99Tcm-3SP and 99Tcm-Teboroxime (99Tcm-TEBO for short) were prepared.Approximately 370 MBq 99Tcm-3SP or 99Tcm-TEBO was injected intravenously in 2 healthy mini-swine separately.Dynamic planar images were acquired immediately after injection and continued for 20 min using a standard SPECT camera.The radioactivity uptakes in the heart,liver,and lungs were measured,and heart/liver and heart/lung ratios over time were calculated.Dynamic SPECT studies were performed in 4 normal swine and 1 AMI-swine using cadmium zinc telluride-SPECT (CZT-SPECT).List mode acquisitions were immediately started and continued for 15 min after intravenous injection of approximately 370 MBq 99Tcm-TEBO and 99Tcm-3SP.The injection of two radiotracers in the same swine was completed within 2 d.The radioactivity uptakes in heart and liver were measured,and heart/liver ratio was calculated.Image quality was also evaluated.Paired t test was used to analyze the data.Results The radiochemical purity of 99Tcm-TEBO or 99Tcm-3SP were both above 95％.The initial heart uptake of 99Tcm-3SP was very close to that of 99Tcm-TEBO (planar image,2 min postinjection:309.32× 103 vs 314.13 × 103 counts/MBq;SPECT image,2 min postinjection (corrected):7.96±0.87 vs 8.24± 1.53,t =0.277,P＞0.05),but the myocardial retention time was much longer than that of 99Tcm-TEBO (planar image,20 min postinjection:218.67× 103 vs 143.19× 103 counts/MBq;SPECT image,15 min postinjection (corrected):6.76±0.45 vs 5.06±0.33,t =-12.412,P =0.001).The uptake of liver and heart/liver ratio between 99Tcm-TEBO and 99Tcm-3SP were similar (t values:-1.332-1.101,all P＞0.05 within 15 min).SPECT MPI images demonstrated uniform tracer distribution with clearly visualizable myocardial boundary in normal myocardium and intense perfusion defect in infarct myocardium.High quality SPECT images could be obtained in any of the 5 min imaging windows over the first 15 min after injection of 99Tcm-3SP in normal swine and AMI-swine.Conclusion 99Tcm-3SP is a promising 99 Tcm-labeled radiotracer for fast-MPI considering its high heart uptake,long myocardial retention time (20 min postinjection) and superior SPECT image quality.
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Objective@#To investigate the impact on myocardial blood flow (MBF) quantitation with multi-pinhole cadmium zinc telluride (CZT)-SPECT with or without partial physical corrections.@*Methods@#A total of 30 patients (18 males, 12 females; age: (63±9) years) with suspected or known coronary heart diseases who underwent dynamic SPECT from July 2018 to January 2019 in Fuwai Hospital were enrolled. Images were reconstructed using different corrections: no correction (NC), partial corrections ((noise reduction (NR), NR+ scatter correction (SC), NR+ SC+ resolution recovery (RR)), NR+ SC+ RR+ attenuation correction (AC; total corrections, TC). Kinetic modeling integrated one-tissue two-compartment model while using index of fitting quality (R2) and fraction blood volume (FBV) to assess the quality of modeling. Rest MBF (RMBF), stress MBF (SMBF) and myocardial flow reserve (MFR) quantified from no correction (NC) or partial corrections were compared with those of TC. Wilcoxon signed rank test and linear regression analysis were used to analyze the data.@*Results@#Compared to TC, NC showed the lowest R2 (rest: 0.69, stress: 0.78; z values: 4.78 and 4.78, both P<0.01) and highest FBV (rest: 0.37, stress: 0.40; z values: -3.40 and -3.30, both P<0.01). The improvement of R2 and FBV was consistent with increased corrective terms. Compared with TC, NC overestimated SMBF and MFR (z values: 1.27 and -3.50, both P<0.01), all partial corrections overestimated RMBF and SBMF (z values: from -4.55 to 1.27, all P<0.01). NR and NR+ SC underestimated MFR (both P<0.05). Linear regression analysis showed that the regressive coefficients of RMBF between NC, NR, NR+ SC, NR+ SC+ RR and TC were 0.908-1.210, and Bland-Altman plots of RMBF demonstrated positive or negative biases (-0.07, 0.21, 0.26, 0.15 ml·min-1·g-1). The regression coefficients of SMBF were 1.129-1.308, and Bland-Altman plots demonstrated positive biases (0.60, 0.25, 0.28, 0.24 ml·min-1·g-1). The regression coefficients of MFR were 0.907-1.318, and Bland-Altman plots demonstrated positive or negative biases (0.70, -0.11, -0.05, 0.01).@*Conclusion@#Full physical corrections can improve the index of fitting quality in the kinetic modeling and reduce left ventricle spillover, which help to warrant the accuracy of SPECT myocardial blood flow quantitation with multi-pinhole CZR-SPECT.
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Objective To investigate the impact on myocardial blood flow (MBF) quantitation with multi-pinhole cadmium zinc telluride (CZT)-SPECT with or without partial physical corrections. Methods A total of 30 patients (18 males, 12 females; age: (63±9) years) with suspected or known coronary heart diseases who underwent dynamic SPECT from July 2018 to January 2019 in Fuwai Hospital were enrolled. Images were reconstructed using different corrections: no correction (NC), partial corrections ((noise re-duction ( NR) , NR+scatter correction ( SC) , NR+SC+resolution recovery ( RR) ) , NR+SC+RR+attenua-tion correction ( AC;total corrections, TC) . Kinetic modeling integrated one-tissue two-compartment model while using index of fitting quality ( R2 ) and fraction blood volume ( FBV) to assess the quality of modeling. Rest MBF ( RMBF) , stress MBF ( SMBF) and myocardial flow reserve ( MFR) quantified from no correc-tion ( NC) or partial corrections were compared with those of TC. Wilcoxon signed rank test and linear re-gression analysis were used to analyze the data. Results Compared to TC, NC showed the lowest R2( rest:0.69, stress:0.78;z values:4.78 and 4.78, both P<0.01) and highest FBV ( rest:0.37, stress:0.40;z values: -3.40 and -3.30, both P<0.01). The improvement of R2 and FBV was consistent with increased corrective terms. Compared with TC, NC overestimated SMBF and MFR ( z values:1.27 and-3.50, both P<0.01), all partial corrections overestimated RMBF and SBMF (z values:from -4.55 to 1.27, all P<0.01). NR and NR+SC underestimated MFR (both P<0.05). Linear regression analysis showed that the regressive coefficients of RMBF between NC, NR, NR+SC, NR+SC+RR and TC were 0.908-1.210, and Bland-Altman plots of RMBF demonstrated positive or negative biases (-0.07, 0.21, 0.26, 0.15 ml·min-1·g-1). The regression coefficients of SMBF were 1. 129-1. 308, and Bland-Altman plots demonstrated positive biases (0. 60, 0.25, 0.28, 0.24 ml·min-1·g-1). The regression coefficients of MFR were 0.907-1.318, and Bland-Altman plots demonstrated positive or negative biases (0.70,-0.11,-0.05, 0.01). Conclusion Full physical corrections can improve the index of fitting quality in the kinetic modeling and reduce left ventricle spillover, which help to warrant the accuracy of SPECT myocardial blood flow quantitation with multi-pin-hole CZR-SPECT.
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Objective To evaluate the effect of anticoagulant therapy by pulmonary ventilation/perfusion (V/Q) imaging in chronic thromboembolic pulmonary hypertension (CTEPH) patients.Methods Thirtysix CTEPH patients (16 males,20 females,average age:(53.8±13.8) years) diagnosed by pulmonary angiography from January 2013 to December 2015 were included in this retrospective study.All patients received anticoagulant therapy for more than 6 months.They underwent pulmonary V/Q imaging before and 6 months after anticoagulant therapy.The numbers of pulmonary segments with perfusion defect,percentage of perfusion defect score (PPDs) and pulmonary arterial systolic pressure (PASP) before and after anticoagulant therapy were measured by echocardiography.Pair t test was used for data analysis.Results Before anticoagulant therapy,there were 319 pulmonary segments with perfusion defect in 36 CTEPH patients,8.9± 3.4 on average,and reduced to 8.4+3.6 after anticoagulant therapy (t =3.101,P＜0.01).The PPDs before and after anticoagulant therapy were (43.3±19.7)％ and (40.8±+20.5)％ (t=2.364,P＜0.05).In the subgroup of 9 patients with improved pulmonary perfusion,the PASP significantly decreased from (68.7±27.3)to (56.1 +±34.8) mmHg (1 mm Hg =0.133 kPa;t =2.465,P＜ 0.05) after anticoagulant therapy.In contrast,in the subgroup of 27 patients with no improved pulmonary perfusion,the PASP before and after anticoagulant therapy were (71.3±26.9) and (76.7±35.0) mmHg respectively (t=-1.511,P＞0.05).Conclusion Pulmonary V/Q imaging is a reliable method for evaluating the changes of pulmonary perfusion before and after anticoagulant therapy,and it is valuable for assessing the effect of anticoagulant therapy in CTEPH patients.
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OBJECTIVE@#To test the acute and chronic toxicity of topical application of 0.5% podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) to the vaginal mucosa.@*METHODS@#Twelve New Zealand rabbits were randomized into 3 groups and subjected to daily topical applications of normal saline (control group), 0.5% podophyllotoxin tincture (POD-T) or 0.5% POD-NLC on the vaginal mucosa for 10 consecutive days, and the pathological changes in the mucosa were graded using the Eckstein scoring system.The acute toxicity of POD-NLC was tested in 20 SD female rats, which received intravaginal administration of POD-NLC or vehicle for 3 times within 24 h; After 14 days of continuous observation, the rats were dissected for calculating the viscera coefficient.For testing the chronic toxicity of POD-NLC, 80 SD female rats were randomized into 4 groups and subjected to daily intravaginal administration of the vehicle or POD-NLC at low, moderate or high doses for 13 consecutive weeks.The rats were weighed once a week and at the end of the experiment, 2/3 of the rats from each group were sacrificed to collect blood samples, calculate the viscera coefficient, and examine the pathological changes in the liver.The remaining 1/3 rats were observed for another 2 weeks without further drug treatment and the same examinations were performed.@*RESULTS@#In the rabbits, 0.5% POD-NLC elicited only mild irritation while POD-T caused moderate irritation of the vaginal mucosa.In the acute toxicity test, the organ coefficients were comparable between the rats treated with the vehicle and POD-NLC (>0.05).Long-term intravaginal administration of POD-NLC did not produce significant changes in the behavior, activity, body weight, blood biochemical profiles or organ coefficient as compared with the vehicle control group (>0.05).@*CONCLUSIONS@#Intravaginal administration of 0.5% POD-NLC causes very mild irritation without obvious acute or chronic toxicity to the vaginal mucosa in rabbits and rats.
Subject(s)
Animals , Female , Rabbits , Rats , Administration, Intravaginal , Liposomes , Mucous Membrane , Nanostructures , Toxicity , Podophyllotoxin , Toxicity , Random Allocation , VaginaABSTRACT
<p><b>OBJECTIVE</b>To assess the distribution and systemic toxicity of podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) after topical application on the cervical mucosa in Tibet minipigs.</p><p><b>METHODS</b>Twelve Tibet mini-pigs were randomized into test group and control group to receive topical application of 0.5% POD-NLC and 0.5% POD tincture, respectively, on the cervical mucosa. Cervical mucosal irritation, targeted distribution and systemic absorption of POD were observed at different time points within 24 h after the drug application.</p><p><b>RESULTS</b>No local inflammation reaction was observed in the test group, while serious local irritations (swelling, blisters, blood blisters, erosion and ulceration) occurred in the control group. The fluorescence intensity of POD in the mucosal tissue reached the peak level at 4 h after drug application in the control group, while the POD fluorescence intensity increased slowly and reached the peak level at 16 h in the test group. The peak blood POD concentration occurred at 6 h after POD-NLC application in the test group (14.28∓0.33 ng/mL), as compared to 4 h in the control group (42.46∓0.32 ng/mL). At all the time points within 24 h, blood POD concentration remained significantly lower in the test group than in the control group (P<0.05), and the area under curve of blood POD concentration in the control group was 1.38-fold greater than that in the test group.</p><p><b>CONCLUSION</b>POD-NLC allows sustained release of POD and achieves a higher POD concentration in the mucosal tissue without causing local irritation or obvious systemic toxicity in Tibet minipigs.</p>
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<p><b>OBJECTIVE</b>To explore the mechanism of podophyllotoxin nanostructured lipid carriers (POD-NLC)-induced apoptosis of VK2/E6E7 cells mediated by endoplasmic reticulum stress (ERS).</p><p><b>METHODS</b>VK2/E6E7 cells cultured in vitro were exposed to 0.125, 0.25, and 0.5 µg/ml POD-NLC or blank NLC for 24 h. The intracellular calcium concentration was measured by laser scanning confocal microscopy (LSCM), and the expression levels of GRP78, GRP94, and calpain2 mRNA and proteins in the cells were detected using RT-PCR and Western blotting.</p><p><b>RESULTS</b>Compared with the control cells, the cells exposed to POD-NLC showed a concentration-dependent increase of intracellular calcium concentration (P<0.01), and the differences were statistically significant between different dose groups (P<0.05). RT-PCR and Western blotting showed that POD-NLC up-regulated GRP78, GRP94 and calpain2 mRNA and proteins expressions, which showed significant differences between blank-NLC and the control groups (P>0.05).</p><p><b>CONCLUSION</b>POD-NLC induces apoptosis of VK2/E6E7 cells possibly by triggering the endoplasmic reticulum stress response.</p>
Subject(s)
Humans , Apoptosis , Calcium , Metabolism , Calpain , Metabolism , Cell Line , Endoplasmic Reticulum Stress , HSP70 Heat-Shock Proteins , Metabolism , Heat-Shock Proteins , Metabolism , Membrane Proteins , Metabolism , Nanostructures , Chemistry , Podophyllotoxin , Chemistry , RNA, MessengerABSTRACT
<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of sorafenib and liposome doxorubicin on poorly differentiated thyroid carcinoma (PDTC) xenografts in nude mice.</p><p><b>METHODS</b>Sorafenib and liposome doxorubicin were applied to PDTC xenografts in nude mice. The mice were randomized into seven groups: blank control (A), vehicle control (B), single liposome doxorubicin (C), single sorafenib group (D), liposome doxorubicin combined with low dose sorafenib group (E), combined group with medium dosage of sorafenib (F), combined group with high-dose of sorafenib(G). The volume, weight and growth inhibition rate of tumours were measured to evaluate the therapeutic effects of drugs.</p><p><b>RESULTS</b>Sorafenib and liposome doxorubicin showed significant antitumor activity in the PDTC xenografts. The mean tumor volumes of seven groups were (1274.13 ± 393.76) mm(3), (1060.00 ± 469.05) mm(3), (726.76 ± 488.22) mm(3), (451.54 ± 97.75) mm(3), (518.37 ± 164.44) mm(3), (310.51 ± 210.53) mm(3), and (228.44 ± 129.21) mm(3), respectively. The mean tumor weights of the seven groups were (1.13 ± 0.42)g, (0.91 ± 0.39)g, (0.78 ± 0.45)g, (0.55 ± 0.17) g, (0.52 ± 0.19) g, (0.34 ± 0.21) g, and (0.19 ± 0.09) g separately. The tumor inhibition rates of group C to G were 30.8%, 40.8%, 42.3%, 62.9%, 72.6% separately.</p><p><b>CONCLUSIONS</b>Sorafenib and liposome doxorubicin, no matter for single agent or in combination, showed significant antitumor activity in the PDTC PDTC xenografts in vivo. The tumour-inhibited effect of single sorafenib is better than that of single liposome doxorubicin. Liposome doxorubicin combined with medium dosage of sorafenib had a better therapeutic effect and less side effects.</p>
Subject(s)
Animals , Humans , Mice , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Doxorubicin , Liposomes , Mice, Nude , Niacinamide , Phenylurea Compounds , Thyroid Neoplasms , Drug Therapy , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of pcDNA3.1-Egr.1p-p16 plasmid on apoptosis and cell cycle of pancreatic carcinoma JF305 cell line.</p><p><b>METHODS</b>JF305 cells were cultured and transfected with pcDNA3.1-Egr.1p-p16 plasmid via Lipofectamine(TM) 2000, followed by irradiation by 6MV-X at 4 Gy (dose rate 2.50 Gy/min). The cell cycle and cell apoptosis changes were analyzed by flow cytometry.</p><p><b>RESULTS</b>In cells infected with pcDNA3.1-Egr.1p-p16 plasmid and those with pcDNA3.1-Egr.1p-p16 plasmid infection before 4 Gy irradiation, the percentages of viable apoptotic cells were 6.4% and 10.4%, and those of advanced stage apoptotic or dead cells were 16.8% and 33.8%, significantly higher than those in the control group (P<0.05). JF305 cell apoptosis in 4 Gy irradiation group was obviously increased in comparison with non-irradiated plasmid-infected cells (P<0.05). Irradiation resulted in a predominant G(2) arrest of the plasmid-infected JF305 cells. Both pcDNA3.1-p16 plasmid and pcDNA3.1-Egr.1p-p16 plasmid infections could induce G1 arrest of JF-305 cells, and irradiation did not produce significant changes in G(1)-arrested cells in the two plasmid infection groups, but cells arresting at G(2) phase increased.</p><p><b>CONCLUSION</b>pcDNA3.1-Egr.1p-p16 can induce JF-305 cells apoptosis, which is enhanced by irradiation. pcDNA3.1-Egr.1p-p16 tranfection may result in G(1) arrest of the cells, and when combined with irradiation, the cells arrested at G(2) phase can increase.</p>
Subject(s)
Animals , Humans , Apoptosis , Genetics , Radiation Effects , Cell Cycle , Genetics , Radiation Effects , Cell Line, Tumor , Genes, p16 , Genetic Therapy , Plasmids , Genetics , Radiation Dosage , Radiotherapy , Time Factors , TransfectionABSTRACT
Objective To explore the value of tubercular antibody (TBAb) in the diagnosis of tuberculous pericarditis (TBP).Methods The TBAb in 38 patients were determined by colloidal gold (CG) and compared with 64 healthy control. Results The positive ratio in TBP group was significantly higher as compared with control group. The hydropericardium was significantly decreased or disappeared after 6 months of antituberculotic treatment by color Doppler ultrasonography. It seemed that patients were rehabilitated and electrocardiogram (ECG) was normal. Conclusion TBAb is valuable in the diagnosis,differential diagnosis or treatment of TBP.
ABSTRACT
<p><b>OBJECTIVE</b>To compare the prognostic efficacy of three clinical staging systems: the Chinese system (CS), CLIP scores, and TNM for hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>107 cases diagnosed as HCC between January 2000 and October 2003 were retrospectively analyzed. Their clinical stages were decided on the basis of data in CLIP or Chinese staging system when the HCC diagnosis had been confirmed. Fifty-three of the 107 patients underwent surgical resection. The TNM stage was therefore determined according to surgico-pathological results. The survival of those patients with respective to different stages were analyzed and compared using Kaplan-Meier curves and Log rank method.</p><p><b>RESULTS</b>All the patients were followed up after treatment. The 3-year survival rate in the CS Ia, Ib and CLIP 0 group were 100%. The 1- and 2-year survival rates of CS IIIa group was 68% and 51%, respectively. The 1-year survival in CS IIIb group was only 20.9%. The 1-, 2-, and 3-year survival rate in patients with a CLIP score beyond 4 was 57.1%, 49.9%, and 33.5%, respectively. In patients treated with surgical resection, the CS Ia group and TNM I group had a 3-year survival rate of 100%. The 1- and 3-year survival rate in CS IIb were 83.3% and 75.0%, in TNM III group 93.7% and 77.5%.</p><p><b>CONCLUSION</b>The CLIP system may provide accurate prediction of prognosis based on early clinical features. The CS system is comparably efficient in predicting the prognosis of HCC patients, particularly in patients with severe cirrhosis.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular , Mortality , Pathology , General Surgery , Liver Neoplasms , Mortality , Pathology , General Surgery , Neoplasm Staging , Methods , Prognosis , Retrospective Studies , Survival RateABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic measures for unresectable primary liver cancer (PLC).</p><p><b>METHODS</b>The date of 312 unresectable primary liver cancer patients treated from January 1991 to March 2003 were retrospectively analyzed.</p><p><b>RESULTS</b>Of these 312 patients, 73 were treated by cryosurgery-based combined modality therapy, 239 were treated by a TACE-oriented combined modality therapy. 289 patients except 23 were followed for a period of 2 to 156 months. The overall 1-,3- and 5-year survival rate in this series was 74. 0% , 34. 0% and 16. 7% , respectively. The 1-,3-and 5-year survival rate in the cryosurgery group was 64. 4% , 38. 4% and 27. 4% , respectively. The 1-, 3- and 5-year survival rate in the TACE group was 75. 1% , 29. 0% and 10. 0%, respectively.</p><p><b>CONCLUSION</b>Treatment for the unresectable primary liver cancer should be individualized and combined with suitable therapeutic modalities.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Chemoembolization, Therapeutic , Methods , Combined Modality Therapy , Cryosurgery , Follow-Up Studies , Liver Cirrhosis , Therapeutics , Liver Neoplasms , Pathology , Therapeutics , Neoplasm Recurrence, Local , Retrospective Studies , Survival AnalysisABSTRACT
OBJECTIVE@#To investigate the optimal doses of X-ray irradiation and plasmid injection in the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in vivo.@*METHODS@#We observed the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy with different doses of X-ray irradiation (2, 10, 20 Gy) and plasmid injection (10, 20, 30 microg) in nude mice with JF-305 pancreatic carcinoma, and detected the expression of p16 in tumor by RT-PCR.@*RESULTS@#The tumor growth rate of the nude mice irradiated locally with 20 Gy X-rays after the plasmid injection was significantly lower (P < 0.05 ) than that of the nude mice irradiated locally with 2 Gy or 10 Gy X-ray 3 days after the irradiation. The tumor growth rate of the nude mice injected locally with 20 microg or 30 microg plasmid was significantly lower (P <0.05 ) than that of the nude mice injected locally with 10 microg plasmid. Both pcDNA3. 1-Egr. 1p-p16 group and pcDNA3. 1-Egr. 1p-p16 +20 Gy group had p16 mRNA expression, but the mRNA level of pcDNA3. 1-Egr. 1p-p16 +20 Gy group was higher than that of pcD- NA3. 1-Egr. 1p-p16 group.@*CONCLUSION@#In the pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in vivo the optimal dose of X-ray irradiation was 20 Gy and the optimal dose of plasmid injection was 20 microg. The anti-tumor effect of pcDNA3. 1-Egr. 1p-p16 combined with radiotherapy is better than that of radiotherapy or gene therapy alone, which may be related with the enhanced p16 expression in tumor after the irradiation.
Subject(s)
Animals , Female , Mice , Combined Modality Therapy , DNA , Genetics , Early Growth Response Protein 1 , Genetics , Genes, p16 , Genetic Therapy , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Pancreatic Neoplasms , Radiotherapy , Therapeutics , Recombinant Proteins , MetabolismABSTRACT
Objective To investigate the clinicopathological features, postoperative survival and prognostic influencing factors of male patients with hepatocellular carcinoma (HCC). Methods The clinicopathological features and the follow-up data of 155 male HCC patients who received hepatectomy from Jan. 1995 to Dec. 2002 were retrospectively analyzed and the prognostic influencing factors were defined by uni-and multi-variate analysis. Results Compared with 24 female patients at the same period, males were about six-year older and both of their hepatitis B surface antigen (HBsAg) and liver cirrhosis positive rates were higher (P