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Objective @#To investigate the effect and mechanism of methyltransferase-like 3 (METTL3) on the pro- liferation , migration , and secretion of inflammatory factors by synovial fibroblasts from rheumatoid arthritis (RA) .@*Methods @#The expression of METTL3 in synovial tissue (SF) from 25 patients with rheumatoid arthritis and 25 pa- tients with osteoarthritis was detected by RT-qPCR and immunohistochemistry , respectively . The concentration of RNA m6A was detected by ELISA . RA synovial fibroblasts were isolated and cultured , and divided into NC ( nor- mal control) group , hi-METTL3 (overexpression of METTL3) group , si-METTL3 (knock-down METTL3) group , and STM2457 (METTL3 specific inhibitor) intervention group . Cell proliferation was detected by CCK-8 method . Apoptosis was detected by flow cytometry . And the concentrations of interleukin-6 ( IL-6) , interleukin-17A ( IL- 17A) , receptor activator of nuclear factor-kappa B ligand (RANKL) , and osteoprotegerin (OPG) in the superna- tant of cell culture were detected by ELISA . @*Results @#Compared with synovial tissue of osteoarthritis , the expres- sion of mRNA m6A and METTL3 in synovial tissue of RA significantly increased (P < 0. 05) . After overexpression of METTL3 , the expression of m6A in synovial fibroblasts increased . The proliferation and migration abilities of SF in hi-METTL3 group were significantly improved , and their apoptosis did not change significantly . The secretion of cytokines IL-6 and RANKL of SF in hi-METTL3 group significantly increased , while the OPG significantly de- creased (P < 0. 05) . After interfering with METTL3 expression , the expression of m6A in synovial fibroblasts de- creased . Cell proliferation and migration of SF in siMETTL3 group significantly decreased . The secretion of cyto- kines IL-6 and RANKL significantly decreased , and OPG significantly increased ( P < 0. 05) . After intervention with METTL3 inhibitor STM2457 , the proliferation and migration of synovial fibroblasts were significantly reduced , and the secretion of cytokines IL-6 and RANKL significantly reduced , and OPG significantly increased ( P < 0. 05) . There was no significant difference in the expression of IL-17A among each group . @*Conclusion @#METTL3 may promote the proliferation and migration of RA synovial fibroblasts , enhance the expression of IL-6 and RANKL , and inhibit the expression of OPG through RNA m6A methylation modification .
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Objective:To explore the clinical application value of personalized positioning using a cervical collar combined with a vacuum pad in the Cyberknife radiosurgery for cervical spine metastases.Methods:This study enrolled 68 patients with cervical spine metastases to be treated with Cyberknife stereotactic radiotherapy for cervical spines. These patients consisted of 41 males and 27 females, aged from 43 to 78 years (average: 51.5 years). They were divided into groups A, B, and C using the random number table method. The patient positioning in these groups was achieved using a cervical collar combined with a vacuum pad (personalized positioning), a vacuum pad, and a small head mold, respectively. After the first treatment, the comfort levels of the positioning molds during treatment were investigated. After radiotherapy, the average deviations in translational and rotational directions, the minimum tolerance distance (dxAB), the minimum rotational deviation angle (drAB), the proportion of false nodes, and the comfort level of the three positioning method were acquired for analysis.Results:The three groups showed statistically significant differences in the inf-sup, left-right, ant-post, pitch, roll, and yaw directions during the first treatment ( F = 7.13, 2.56, 3.41, 4.21, 2.71, 8.14, P < 0.05). Compared with groups B and C, Group A had significantly lower dxAB, drAB, and the proportion of false nodes, showing statistically significant differences ( F = 5.06, 4.31, 3.30, P < 0.05). Furthermore, patients in groups A and B felt more comfortable with the positioning molds than those in Group C ( χ2 = 12.46, P < 0.05), with no statistically significant differences between groups A and B ( P > 0.05). Conclusions:For patients with cervical spine metastases undergoing Cyberknife radiosurgery for cervical spines, the personalized positioning using a cervical collar combined with a vacuum pad can improve the accuracy and safety of Cyberknife spinal tracking while remaining the comfort level.
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Electrocardiogram (ECG) signal is an important basis for the diagnosis of arrhythmia and myocardial infarction. In order to further improve the classification effect of arrhythmia and myocardial infarction, an ECG classification algorithm based on Convolutional vision Transformer (CvT) and multimodal image fusion was proposed. Through Gramian summation angular field (GASF), Gramian difference angular field (GADF) and recurrence plot (RP), the one-dimensional ECG signal was converted into three different modes of two-dimensional images, and fused into a multimodal fusion image containing more features. The CvT-13 model could take into account local and global information when processing the fused image, thus effectively improving the classification performance. On the MIT-BIH arrhythmia dataset and the PTB myocardial infarction dataset, the algorithm achieved a combined accuracy of 99.9% for the classification of five arrhythmias and 99.8% for the classification of myocardial infarction. The experiments show that the high-precision computer-assisted intelligent classification method is superior and can effectively improve the diagnostic efficiency of arrhythmia as well as myocardial infarction and other cardiac diseases.
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Humains , Électrocardiographie , Cardiopathies , Infarctus du myocarde/imagerie diagnostique , Algorithmes , Alimentations électriquesRÉSUMÉ
Objective:To investigate the consistency and correlation of the respiratory synchronization tracking and fiducial marker respiratory synchronization tracking in the Cyberknife stereotactic body radiotherapy (SBRT) with the diaphragm as the tracking target.Methods:A total of 11 patients hospitalized at Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from April 2018 to November 2019 were enrolled, including 8 cases of lung cancer, 2 cases of liver cancer with lung metastasis and 1 case of colorectal cancer with lung metastasis. All enrolled cases used fiducial marker tracking plan (RT) and diaphragm contour tracking plan (DT), and then all received tumor visualization simulation tests. Bland-Altman method was used to make the consistency analysis of the offset in the visualization tests process of 2 tracking plans at each respiratory time point. The minimum tolerance distance, uncertainty and average standard deviation and maximum standard deviation in the optimal model state plans were compared between the both plans by using t test. Results:Compared with RT, the translational standard deviations of DT tracking were listed as follows: head-foot direction (0.4±2.9) mm, left-right direction (0.3±4.4) mm, anterior-posterior direction (-1.8±6.8) mm. The Bland-Altman method showed that the consistency between RT and DT was better in the head-foot and left-right directions, and worse in the anterior-posterior direction; the synchronization was only better in the head-foot direction, and worse in both the left-right and anterior-posterior directions. Results of the model quality comparison showed that the uncertainty of RT was higher than that of DT, and the difference was statistically significant [(23±6)% vs. (9±4)%, t=-5.24, P = 0.001], while the differences of the minimum tolerance distance, average standard deviation and maximum standard deviation were not statistically significant (all P>0.05). Conclusions:Patients who use respiratory synchronization Cyberknife SBRT with the diaphragm as the tracking target have better consistency and synchronization in the head-foot direction, but worse in the left-right and anterior-posterior directions. Under the corresponding marginal margin of the target area in the left-right direction, for tumors near the diaphragm that are not visible in the visual test, it is potentially feasible to use the diaphragm as a tracking target to implement respiratory synchronization SBRT. For larger motion amplitudes in the left-right and anterior-posterior directions, more caution is required.
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Objective:To investigate the changes and clinical significance of prothrombin time (PT) during chemotherapy for non-Hodgkin lymphoma (NHL) in high-altitude area and low-altitude area, and understand the relationship between NHL and PT.Methods:From August 2018 to September 2019, data of 68 cases of NHL patients in the Fifth People′s Hospital of Qinghai Province in the high-altitude area (average altitude: 2 261 m) and the Tianjin Fourth Central Hospital in the low-altitude area (average altitude: 1.3 m) were collected and compared with those of 20 subjects from health examination. The patients were divided into groups according to the NHL classification, stage and grade (international prognostic index, IPI score), the PT at initial diagnosis was compared. The PT changes before and after chemotherapy (6 cycles) were compared between high-altitude area and low-altitude area.Results:The PT in healthy subjects and PT at initial diagnosis in NHL patients in low-altitude area were lower than those in high-altitude area: (12.3 ± 1.3) s vs. (13.4 ± 1.9) s, (12.2 ± 0.8) s vs. (13.7 ± 1.1) s, and there was statistical difference ( P<0.05). There was no significant difference between NHL patients and healthy patients in the same area ( P>0.05). In NHL patients in high-altitude area and low-altitude area, PT of different NHL classification, stage and grade were statistically significant ( t = 4.611, 8.202, 6.893, 5.345, 3.121, 5.397, 2.838 and 3.720, P<0.05). In the same altitude area, NHL classification, stage and grade of NHL patients had no significant effect on PT, and there were no statistically significant difference ( P> 0.05); in NHL patients, there were statistically significant differences in PT before and after chemotherapy between high-altitude area and low-altitude area: (13.7 ± 1.1) s vs. (12.2 ± 0.8) s, (13.4 ± 1.4) s vs. (12.0 ± 1.3) s, and there were statistical differences ( P<0.05), and no significant changes in PT before and after chemotherapy in the same altitude area ( t = 1.377 and -1.222, P>0.05). Conclusions:PT of NHL patients in low-altitude area is lower than that in high-altitude area, and there is no significant correlation with NHL classification, stage, grade and chemotherapy in NHL patients.
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Objective:By comparing the comprehensive differences between volume-modulated arc therapy (VMAT)-and CyberKnife-6D Skull (CK-6D Skull) tracking technology-based stereotactic radiotherapy (SRT) plans in the treatment of multiple brain metastatic tumors, and explore the advantages of multi-target intracranial technology.Methods:Clinical data of 42 patients with more than 2 brain metastases who received STR between January 2017 and August 2018 were retrospectively analyzed. For each patient, two radiotherapy plans were designed by selecting CK-6D Skull and VMAT technologies. The quality of VMAT and CK-6D Skull was compared by calculating the gradient index (GI), dose sag volume and organ at risk (OAR) of target area. The total number of monitor unit and single treatment time were recorded to compare the execution efficiency of these two technologies.Results:The GI of intracranial 2-target and 3-target plans of CK-6D Skull technology was significantly superior to that of VMAT technology ( P<0.05). The GI did not significantly differ between the 4-target and the 5-target groups ( P>0.05). The contribution of these two technologies to the maximum dose of OAR was not significantly different ( P>0.05), whereas the treatment time of VMAT technology was shorter ( P<0.05). Conclusions:Both technologies can meet the requirements of clinical SRT for multiple brain metastatic tumors. From the perspective of treatment plan and implementation, SRT based on CK-6D skull technology is recommended for patients with less than 4 intracranial metastatic tumors, and VMAT-based SRT is considered for those with > 4 metastatic tumors. Patients with poor physical condition and difficulty in maintaining a fixed position for a long time shall give priority to VMAT technology. More differences between these two technologies in the implementation of SRT for intracranial multiple brain metastases remain to be elucidated by more case data for statistical analysis.
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Objective@#To explore the effectiveness and safety of ultrasound-guided radiofrequency ablation (RFA) in treatment of thyroid benign nodules.@*Methods@#We analyze 573 patients with thyroid benign nodules from June 2014 to September 2017 treated by RFA at Department Ⅱof Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University. Among these patients, there were 75 males and 498 females, with a median age of 45 years old. All patients were diagnosed as thyroid benign nodules by ultrasound-guided fine needle aspiration biopsy before RFA. A total of 750 benign tumors were treated. To evaluate the thyroid function of the patients before RFA and 3 months after it, and to observe the changes of thyroid benign nodules by ultrasound at 3, 6, 12 months after RFA. The paired t-test was used to compare the measurement data with normal distribution, and Wilcoxon's signed rank test was used to compare the measurement data with non-normal distribution. To calculate the volume change and reduction rate of thyroid benign nodules.@*Results@#RFA was successfully completed in all patients, the volume reduction rate was 67%(48%, 83%) in the 3rd month after RFA, in the 6th month was 81%(67%, 91%), in the 12th month was 89%(80%, 95%). Eighteen patients felt pain during RFA, but the pain was alleviated after stopping ablation. Three patients′ tone decreased, but recovered in a week. Hoarseness occurred in 6 patients and recovered in 3 months. Three patients had neck hemorrhage, which was managed with simple compression of the neck.@*Conclusions@#RFA is an effective and safe treatment for thyroid benign nodules and has obvious advantages such as less invasiveness, having no influence in thyroid functions. It is clinically prospective for application.
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Objective To explore the effectiveness and safety of ultrasound-guided radiofrequency ablation (RFA) in treatment of thyroid benign nodules.Methods We analyze 573 patients with thyroid benign nodules from June 2014 to September 2017 treated by RFA at Department Ⅱ of Thyroid Surgery,the First Affiliated Hospital of Zhengzhou University.Among these patients,there were 75 males and 498 females,with a median age of 45 years old.All patients were diagnosed as thyroid benign nodules by ultrasound-guided fine needle aspiration biopsy before RFA.A total of 750 benign tumors were treated.To evaluate the thyroid function of the patients before RFA and 3 months after it,and to observe the changes of thyroid benign nodules by ultrasound at 3,6,12 months after RFA.The paired t-test was used to compare the measurement data with normal distribution,and Wilcoxon's signed rank test was used to compare the measurement data with non-normal distribution.To calculate the volume change and reduction rate of thyroid benign nodules.Results RFA was successfully completed in all patients,the volume reduction rate was 67% (48%,83%) in the 3rd month after RFA,in the 6th month was 81% (67%,91%),in the 12th month was 89% (80%,95%).Eighteen patients felt pain during RFA,but the pain was alleviated after stopping ablation.Three patients' tone decreased,but recovered in a week.Hoarseness occurred in 6 patients and recovered in 3 months.Three patients had neck hemorrhage,which was managed with simple compression of the neck.Conclusions RFA is an effective and safe treatment for thyroid benign nodules and has obvious advantages such as less invasiveness,having no influence in thyroid functions.It is clinically prospective for application.
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Objective@#To improve synchrony tracking components of CyberKnife (tracking vest and tracking markers) and to analyze the clinical application value of the improved tracking components in CyberKnife treatment of thoracic and abdominal tumors.@*Methods@#The tracking apron was made of knitted four-side elastic spandex cloth and suture design of Velcro, which was used to stick the tracking markers on the chest and abdomen of patients. The tracking markers added a 2 cm thick light foam block to the bottom of the original markers, and then the hook face of the Velcro was fixed to the bottom of the light foam. The improved trace component (the improved component) and the original component (the vendor component) were applied to the lung tracking treatment model, and the manufacturer components were included in the reference group. Adoption of improved components into the observation group; 20 different types of respiratory waveforms were simulated and applied to the same mold plan. After treatment, the coverage rate, mean standard deviation, maximum standard deviation and the slope of XYZ-axis vs. R correlation graph were recorded. The relevant parameters of Synchrony model and wearable time of two components were compared, and the application significances of the improved tracking component in the breathing tracking process of the CyberKnife were evaluated.@*Results@#The maximum slope [median(interquartile range)] of XYZ-axis vs. R related graph in the reference group was 0.73 (3.89), 0.27 (0.49) and 0.34 (1.02), respectively. The maximum slope of XYZ-axis vs. R related graph in the observation group was 0.70 (2.78), 0.31 (0.30) and 0.36 (0.75), respectively. There was no statistically significant difference in the slope of XYZ-axis vs. R between the reference group and the observation group (all P > 0.05). There was no significant difference in the average standard error and maximum standard error between the reference group and the observation group [(1.7±0.4) mm vs. (1.7±0.5) mm, t=-0.382, P= 0.710; (2.0±0.6) mm vs. (1.7±0.5) mm, t=-0.877, P= 0.401], and the difference of the model coverage rate between the two groups was statistically significant [(48±18)% vs. (60±22)%, t= 2.762, P= 0.042]. The setup time of tracking components in the observation group was less than that in the reference group, and the difference was statistically significant [(44±24) s vs. (81±15) s, t=-4.310, P= 0.001].@*Conclusions@#The improved tracking components are comparable to the manufacturer tracking components in the standard error of the Synchrony model. The improved components shorten the wear time and appropriately improve the coverage of the Synchrony model.
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Objective To compare the diagnostic efficacy of 68Ga-prostate specific membrane antigen (PSMA)-617 PET/CT and multi-parameter MRI for primary prostate cancer.Methods From June 2017 to November 2017,24 patients (age (67.6±7.0) years) with suspected prostate cancer were prospectively enrolled.All patients underwent 68Ga-PSMA-617 PET/CT and multi-parameter MRI.Pathological diagnosis was considered as the gold standard.The diagnostic efficacy of the two methods was analyzed and the difference was evaluated by receiver operating characteristic (ROC) curve analysis(Z test).Results Based on the puncture biopsy and/or excision biopsy,18 patients were diagnosed as prostate cancer and 6 patients were diagnosed as benign diseases.According to the five-zone analysis for the prostate (24 patients with 120 zones),48 and 56 zones were detected accurately in prostate cancer patients by PET/CT and multi-parameter MRI respectively,which was 54 and 41 for benign patients.The cut-off value of maximum standardized uptake value (SUVmax) in 68Ga-PSMA-617 PET/CT for diagnosing prostate cancer was 4.85,the area under curve (AUC),sensitivity,specificity,positive predictive value,negative predictive value,accuracy and Youden index were 0.890,75.00% (48/64),96.43% (54/56),96.00% (48/50),77.14% (54/70),85.00%(102/120),71.43% respectively for prostate cancer by PET/CT,and 0.837,87.50%(56/64),73.21% (41/56),78.87% (56/71),83.67% (41/49),80.83% (97/120) and 60.71% respectively by multi-parameter MRI.The difference of AUC was statistically significant (Z=2.82,P<0.01).Conclusions The diagnostic accuracy of 68Ga-PSMA-617 PET/CT imaging for prostate cancer is higher than that of multi-parameter MRI.Both modalities have high diagnostic efficiency and can be used scientifically as complementary.
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Objective To explore the clinical value of an auxiliary set-up method with fiducial markers and Synchrony tracking implanted in spine during Cyber-knife stereotactic radiotherapy by comparing the rotational setup errors between auxiliary setup with less than and more than three fiducial markers.Methods A total of 145 cases of tumor patients with fiducial tracking and Synchrony tracking were selected for radiotherapy,including 94 cases in the observation group (<3 fiducial markers) and 51 cases in the control group (≥ 3 fiducial markers).Before treatment,one spinal alignment plan was added to all the cases in the observation group,and the rotation deviation of the selected spinal distance and the assisted spinal alignment correction of the fiducial marker tracking and the fiducial marker respiratory tracking were counted respectively,and the result of the rotation deviation calculated in the observation group and the control group were analyzed.Results Fiducial tracking spine auxiliary setup result:fiducial marks and selected the spine center distance < 20,20-40,40-60,60-80 and > 80 mm rotating statistical average deviation (0.494±0.350) °,(1.291±0.590) °,(1.705±0.739) °,(2.512±0.761) ° and (2.796± 1.081) °,respectively,rotate observation group and control group total deviation (1.742±0.784) °,(1.805±0.562) °,respectively.Synchrony tracking result in the above case rotation statistical average deviation was (1.190± 0.547) °,(1.956± 0.735) °,(2.141 ± 0.670) °,(2.957±0.648) ° and (4.027±0.695) °,respectively,while rotation total deviation in observation group and control group (2.619±0.906) °,(2.233 ±0.763) °,respectively.There was no significant difference in the rotation deviation between the assisted spinal set-fup and the calculation of rotation deviation between the fiducial tracking and the synchrony tracking (P > 0.05).Conclusions In the fiducial tracking treatment,the range of rotation deviation for the spinal auxiliary set-up correction increases with the increase of the distance between the fiducial markers and the selected spinal center.When the distance between the fiducial marker and the selected spinal is less than 60 mm,the rotation deviation calculated by the spinal auxiliary setup has the same tumor rotation correction effect as that calculated by the fiducial markers.When less than 3 fiducial markers are available and the minimum distance between the fiducial marks and the center of the adjacent spine is relatively close (< 60 mm),the deviation of the rotation direction of the tumor can be calculated by adding the spinal auxiliary setup plan.
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Objective To evaluate the prevalence of chronic kidney disease (CKD) in Chinese adult health check-up population,and to compare with the prevalence of CKD in the study of the general population as well as the large CKD cross-sectional study in China.Methods Epidemiological studies about CKD in Chinese adults health check-up population from January 2007 to December 2017 were searched in PubMed,SinoMed,CNKI,VIP and Wanfang Data.Meta-analysis of the prevalence of CKD was performed with software of Stata 12.0.Subgroup analyses of CKD staging,urban and rural,as well as geographical areas of the general population were executed.Results Twenty-two studies from adult health check-up population were included (238 349 persons).Egger's regression showed no publication bias (P > 0.05).The unstandardized prevalence rate of CKD was 12.49% (male 12.8%,female 12.5%).The respective unstandardized prevalences of proteinuria,hematuria and eGFR decline were 5.90%,5.83% and 2.75%.The unstandardized prevalences of CKD in urban and rural population were 13.21% and 11.90%.The stages of CKD were mainly concentrated in the early stages.There was no significant difference in the non-standard detection rate of total eGFR decline among the adult medical examination population,the general population and the population studied cross-sectionally (P > 0.05).Furthermore,no significant difference in the non-standard detection rate of total hematuria and male hematuria was found between the adult health check-up population and the general population.In addition,the total proteinuric non-standard detection rate of the adult general population was similar with that of population studied cross-sectionally (P > 0.05).Conclusions The prevalence of CKD in Chinese adults is higher,the overall prevalence is however underestimated.The results of epidemiological investigation in adult health check-up population are similar to those of the general population,especially in men.
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Objective To determine equilibrium solubility and apparent partition coefficient of salicylic acid at 25 ℃,and to provide a theoretical basis for design and preparation of its formulation.Methods Equilibrium solubility and apparent partition coefficient (Papp) of salicylic acid were respectively investigated in water,hydrochloric acid solution (pH 1.0) and phosphate buffer solution system (pH 2.0,3.0,4.0,5.0,6.0,7.0,7.8) at 25 ℃.The shake flask method and HPLC were used.The column was Waters C18 (4.6 mm ×250 mm,5 μn) with the mobile phase as methanol-0.1% phosphoric acid water (47:53).The column temperature was room temperature.The flow rate was 1.0 mL·min-1.The detection wavelength was 270 nm and injection volume was 20 μL.Results Equilibrium solubility of salicylic acid was (2.205 ±0.020) mg·mL-1 at 25 ℃ in Water and its Papp was (6.18 ±0.08).The solubility were (1.169 × 10-3 ±7.40 × 10-6),(2.250 ±0.010),(2.410±0.010),(2.694 ±0.003),(5.208 ±0.010),(5.826 ±0.006),(6.255 ±0.030),(3.353 ±0.070) mg·mL-1,respectively,at hydrochloric acid solution (pH 1.0) and phosphate buffer solution system (pH 2.0,3.0,4.0,5.0,6.0,7.0,7.8),and the corresponding Papp were (16.39 ±0.19),(4.23 ±0.07),(6.03 ±0.11),(5.56 ±0.10),(1.25 ±0.01),(0.27 ± 0.001),(0.08 ± 0.001) and (0.07 ± 0.002),respectively.Conclusion The solubility of salicylic acid increases and its oil-water partition coefficient declines with pH value increasing.Salicylic acid is slightly soluble in water and oil.It belongs to Class Ⅳ drug in Biopharmaceutics Classification System (BCS).
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Objective To quantitatively compare the diagnostic capability of 68Ga-NGR and 18F-FDG in well-differentiated hepatocellular carcinoma (HCC) bearing mice by microPET/CT imaging.Methods The in vitro cellular uptake, in vivo microPET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well-differentiated HCC.The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) cells/xenografts were respectively used as positive and negative reference groups for CD13.The expression of CD13 was qualitatively verified by immunohistostaining.The levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by Western blot test for all 3 types of tumors.Two-sample t test was used for data analysis.Results The in vitro cellular uptake showed that the 68Ga-NGR uptake in SMMC-7721 and HT-1080 cells was higher than that in HT-29 cells, and the 68Ga-NGR uptake was higher than 18F-FDG uptake in SMMC-7721 cells.The in vivo microPET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721 tumor was (2.17±0.21) %ID/g, remarkably higher compared to (0.73±0.26) %ID/g of 18F-FDG uptake (t=8.826, P<0.01).The tumor/liver ratio of 68Ga-NGR was 2.05±0.16, which was 2.03-fold higher than that of 18F-FDG.In the HT-1080 tumors, the uptakes of 68Ga-NGR and 18F-FDG were both high, and the values were (2.46±0.23) %ID/g, (3.47±0.31) %ID/g.The uptake of 68Ga-NGR was significantly lower than that of 18F-FDG in HT-29 tumors: (0.67±0.20) %ID/g vs (3.17±0.29) %ID/g;t=4.221, P<0.01.Western blot and immunohistostaining results were as follows: HT-1080(CD13+, G6Pase-), SMMC-7721(CD13+, G6Pase+), HT-29(CD13-, G6Pase-).Conclusions The uptake of 68Ga-NGR is higher than 18F-FDG uptake in SMMC-7721 tumor bearing mice, therefore it is worthwhile to consider the feasibility of clinical translation for PET/CT in diagnosis of HCC.Furthermore, because of the difference in 68Ga-NGR and 18F-FDG avidities in tumors with different molecular phenotypes of CD13 and G6Pase, there is an underlying potential for molecular imaging in the determination of molecular phenotypes.
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Objective To quantitatively compare the diagnostic capability of 68Ga-NGR and 18F-FDG in well-differentiated hepatocellular carcinoma (HCC) bearing mice by microPET/CT imaging.Methods The in vitro cellular uptake,in vivo microPET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well-differentiated HCC.The human fibrosarcoma (HT-1080) and human colorectal adenocarcinoma (HT-29) cells/xenografts were respectively used as positive and negative reference groups for CD13.The expression of CD13 was qualitatively verified by immunohistostaining.The levels of CD13 and glucose-6-phosphatase (G6Pase) were semi-quantitatively analyzed by Western blot test for all 3 types of tumors.Two-sample t test was used for data analysis.Results The in vitro cellular uptake showed that the 68Ga-NGR uptake in SMMC-7721 and HT-1080 cells was higher than that in HT-29 cells,and the 68Ga-NGR uptake was higher than 18F-FDG uptake in SMMC-7721 cells.The in vivo micro-PET/CT imaging results revealed that the uptake of 68Ga-NGR in SMMC-7721 tumor was (2.17±0.21) %ID/g,remarkably higher compared to (0.73±0.26) %ID/g of 18F-FDG uptake (t =8.826,P<0.01).The tumor/liver ratio of 68Ga-NGR was 2.05±0.16,which was 2.03-fold higher than that of 18F-FDG.In the HT-1080 tumors,the uptakes of 68 Ga-NGR and 18F-FDG were both high,and the values were (2.46±0.23) %ID/g,(3.47±0.31) %ID/g.The uptake of 68Ga-NGR was significantly lower than that of 18F-FDG in HT-29 tumors:(0.67±0.20) %ID/g vs (3.17±0.29) %ID/g;t=4.221,P<0.01.Western blot and immunohistostaining results were as follows:HT-1080(CD13+,G6Pase-),SMMC-7721(CD13+,G6Pase+),HT-29 (CD13-,G6Pase-).Conclusions The uptake of 68Ga-NGR is higher than 18F-FDG uptake in SMMC-7721 tumor bearing mice,therefore it is worthwhile to consider the feasibility of clinical translation for PET/CT in diagnosis of HCC.Furthermore,because of the difference in 68Ga-NGR and 18F-FDG avidities in tumors with different molecular phenotypes of CD13 and G6Pase,there is an underlying potential for molecular imaging in the determination of molecular phenotypes.
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Objective To evaluate the ability of a synthetic PET/NIRF probe,named 18F-PSVue643,on the apoptosis detection in animal models with the anti-cancer drugs therapy,and compare the advantages and disadvantages between PET and NIRF.Methods Cell apoptosis was detected by MTT and flow cytometry in vitro.Established U87MG glioblastoma xenograft tumors in nude mice were treated with retinol and paclitaxel for nine days (for PET imaging) or eleven days (for NIRF imaging) continuously.The uptake values were recorded by ROI and expressed as %ID/g.Results The apoptosis ratios in 10 and 100 nmol/L paclitaxel-treated groups were 7.4% and 7.5%,respectively,and the apoptosis ratio of the control group was 4.3%.The apoptosis could be well detected by both NIRF and PET imaging during the whole process of treatment.However,the amount of probe for PET imaging was only a half of that for optical imaging to get the same apoptosis visualization.Conclusion 18F-PSVue643 is suitable for NIRF and PET imaging in detection of apoptosis,and it may be a promising agent for further clinical studies.
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Surgical resection is the primary treatment for locally advanced rectal cancer,but the local recurrence rate of surgical resection is still at a high level. Preoperative and postoperative chemoradiotherapy not only decreases the local recurrence rate of surgical resection,but also elevates the survival rate and life quality. Recently,adjuvant chemoradiotherapy has been applied as the standard therapy for locally advanced rectal cancer. The application of targeted drugs,new chemotherapy drugs and rapid changing radiotherapy technology provide more approaches to the treatment of locally advanced rectal cancer.
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Objective To prepare dual?modality single?photon emission computed tomography (SPECT)?MRI molecular nanoprobes targeting HAb18G/CD147 expressed on breast cancer cell membranes and investigate the physicochemical and biological properties in vitro. Methods Superparamagnetic iron oxide nanoparticles (SPIOs) were prepared by one?pot reaction method as described. The single?chain antibody fragments HAb18F(ab')2 were conjugated to SPIOs via chemical method and then labeled with 125I using Iodogen method. The final 125I?SPIO?HAbF18(ab')2 nanoprobes were purified. SPIOs or 125I?HAb18F(ab')2 were used as control. We carried preliminary evaluation on their physicochemical properties and biological characteristics in vitro: transmission electron microscope (TEM) and dynamic light scattering (DLS) were used to measure these nanoparticle sizes and the hydrodynamic diameters. The MRI T2 transverse relaxation efficiency of these nanoprobes at different Fe2+concentrations were measured with 1.5 T clinical MR scanner. The 125I?SPIO?HAb18F(ab')2 and 125I?HAb18F(ab')2 radiochemical purity were measured by thin layer chromatography and the radio chemical yield was calculated. We also conducted stability tests in vitro and octanol/water partition coefficient experiments. Two breast tumor cell lines, MDA?MB?231 (HAb18G?overexpressing cells,experimental group) and MDA?MB?468 (control), were used for assessment of cells viability at different Fe2 + concentrations (1, 5, 10, 20, 40 μg/ml) by methyl thiazolyl tetrazolium assay. Specific binding experiments in vitro included two parts:magnetic resonance imaging and radionuclide tests, the above?mentioned breast cancer cell lines were incubated with 125I?SPIO?HAb18F(ab')2 nanoprobes respectively and took MDA?MB?231 cells which were not treated as blank group. First comparing the MR signal intensity differences among experimental group, the control group and blank group, then calculated the rate of MRI signal changes;Two breast tumor cell lines, MDA?MB?231 and MDA?MB?468 were incubated with 125I?SPIO?HAb18F(ab')2 nanoprobes too, then measured radioactivity counting byγcounter at different time and calculated the cell binding rates, and did statistical analysis by using one?way ANOVA. Results The SPIOs were fairly homogeneous with an average core size of (10.32±1.30) nm;the SPIO and 125I?SPIO?HAb18F(ab')2 hydrodynamic diameter of 44.80 and 52.64 nm, and MRI scanning showed that the transverse relaxation efficiency of SPIO and 125I?SPIO?HAb18F(ab')2 were 38.79 and 106.73 mM-1 · s-1, respectively. The radio chemical yield of 125I?SPIO?HAbF18(ab')2 and 125I?HAb18F(ab')2 were 41.90% and 85.50%, respectively. The radio chemical yield of the two groups were >95%, suggesting well stability in vitro. The lipo?hydro partition coefficient values were -0.99 ± 0.03 and-1.49 ± 0.08, respectively, which demonstrated that they were both water?soluble substances. Different Fe2+concentrations (1,5,10,20,40μg/ml) of 125I?SPIO?HAb18F(ab')2 on breast cancer cell lines MDA?MB?231 and MDA?MB?468 showed no significant inhibition of cell proliferation (F values were 0.78, 0.66; P values were 0.58, 0.66). The cell?specific binding experiment showed: MRI signal intensity values on experimental group, the control group and the blank group were (1 670 ± 5), (1 930 ± 8), (2 349 ± 14), respectively, significant differences existed among these groups (F=4 408.48,P=0.000), the rate of signal intensity change of experimental group and the control group were 28.87%,17.78%. SPECT:MDA?MB?231 could uptake 125I?SPIO?HAb18F(ab')2, the cell binding rates were (6.52 ± 0.60)% and (10.52 ± 2.04)% in 20 min and 4 h, respectively.Conclusions Our results suggested that the dual?modality SPECT?MRI nanoprobes 125I?SPIO?HAb18F(ab')2 were prepared successfully with good physicochemical properties and biological characteristics in vitro. These dual?modality molecular imaging nano?probes may have potential to improvearly detection and diagnosis of HAb18G/CD147?expressing cancers and to facilitate the development of HAb18G/CD147?directed interventions.
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Cyclooxygenase-2 (COX-2),the rate-limited enzyme that converts arachidonic acid into prostaglandin,has been found overexpression in many malignant tumors.The overexpression of COX-2 plays an important role in tumor genesis and progression and is closely associated with tumor prognosis,so this enzyme has become one of the potential therapeutic targets.Experimental studies reveal that selective COX-2 inhibitors can enhance the tumor radiosensitivity through a variety of molecular pathways and have a protective effect for normal tissues.Selective COX-2 inhibitors are promising radiotherapy modifiers and the underlying molecular mechanisms still need to be further studied.
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Objective To investigate the arthroscopic inside-out repairing technique(hybrid suture technique) for bucket-handle tear of inside meniscus and present the short-term clinical outcome. Methods Twenty patients with 20 repairable inside meniscus tears were enrolled. With arthroscopic technique,the midbody portion and anterior portion of the lesion were repaired using standard inside-out technique with vertical and interlacing tibial and femoral side arrangement. For the most posterior portion, all-inside suture technique with two posterior portals were performed. For isolated red-white zone tears,fibrin clot was implanted into the repaired region for enhancing the healing pro-ACL injuries were reconstructed simultaneously. Results Twenty patients with 20 meniscal repairs were available for 5-36 (19.2 ± 2.3)months follow-up. Eighteen cases were asymptomatic at the latest clinical evaluation,and joint space tenderness in 2 cases. Twenty cases received MRI evaluation during follow-up, showing that 15 menisci were completely healed, 5 partially healed. Postoperative Lysholm scores of the knee joint function [82-97(90.3 ±1.5) points] were significantly improved compared with their preoperative scores [45-69 (56.7 ± 2.0)points] (P = 0.024).Conclusion For meniscal tears involving red-red and red-white zones,arthroscopic hybrid suture technique provides stable strength along the whole length of injured region, and consequently achieves satisfactory clinical outcomes.