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Objective:To investigate the regulatory effect of miR-26a in radiation-induced heart disease (RIHD) mice.Methods:C57/BL6 mice were used to establish RIHD models. The cardiac function, fibrosis, the expression levels of collagen 1 (COL1) and connective tissue growth factor (CTGF), and miR-26a were detected in RIHD mice. Whether CTGF was the target gene of miR-26a was verified by dual luciferase kit. Moreover, cardiac fibroblasts were transfected with miR-26a up and miR-26a down lentivirus vectors to construct the miR-26a overexpression and underexpression cell models. The expression of CTGF, proliferation, and apoptosis of cardiac fibroblasts were detected.Results:In the RIHD mice, heart function was decreased, myocardial fibrosis was remodeled, the expression levels of COL1 and CTGF were up-regulated, and the expression level of miR-26a was down-regulated. Dual luciferase reporter assay confirmed that CTGF was the target gene regulated by miR-26a. Overexpression of miR-26a could inhibit the expression of CTGF, suppress the proliferation of cardiac fibroblasts, promote cell apoptosis and secrete collagen. Underexpression of miR-26a yielded the opposite results.Conclusion:MiR-26a affects the function of cardiac fibroblasts by targeting CTGF and probably mediates the process of radiation-induced myocardial fibrosis, which may become a new regulatory target of RIHD.
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Objective:To investigate the regulatory role of microRNA in radiation-induced heart disease (RIHD) in mice and provide a new strategy for its treatment.Methods:Based on the Gene Expression Omnibus database (GSE147241), which includes normal heart tissue and irradiation heart tissue, we conducted bioinformatics research and analysis to determine the differentially-expressed genes. Then, thirty male C57/BL6 mice were randomly divided into the control group, irradiation group and miR-133a overexpression intervention group. The heart received single dose of X-ray 20 Gy in the irradiation group and miR-133a overexpression intervention group, but not in the control group, and then fed for 16 weeks. Cardiac function was assessed by echocardiography. Myocardial fibrosis was detected by Masson staining. The expression levels of miR-133a, CTGF, COL-1 and COL-3 mRNA were detected by qRT-PCR. The expression levels of CTGF, COL-1 and COL-3 proteins were detected by western blot.Results:miR-133a was the differentially-expressed gene between the irradiation and control groups. Overexpression of miR-133a could mitigate the decrease in cardiac function and increase in myocardial collagen content ( P<0.01). Meantime, overexpression of miR-133a could down-regulate the expression levels of CTGF, COL-1, COL-3 mRNA and protein ( P<0.01). Conclusions:Radiation increases the synthesis of collagen and leads to myocardial fibrosis remodeling. Overexpression of miR-133a can alleviate the radiation-induced myocardial fibrosis.
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Objective To investigate the value of 18F-fluorodeoxyglucose (FDG) PET/CT imaging and cardiac MRI (CMR) in the diagnosis of radiation-induced heart disease (RIHD) in Beagle models.Methods Twenty-four normal male Beagle dogs (1-year old) were randomly divided into control group and irradiated groups (3-month,6-month and 12-month after radiation).The left anterior myocardium of Beagle dogs in irradiated groups was irradiated locally with a single dose of 20 Gy X-ray.Cardiac 18F-FDG PET/CT imaging and CMR were performed on all dogs,and the mean standardized uptake value (SUVmax) and the area of lesions with increased 18F-FDG uptake were obtained.After imaging examinations were finished,dogs were sacrificed and their hearts were taken out to perform Masson staining and electron microcopy.Oneway analysis of variance was used for data analysis.Results There was basically no uptake in myocardium in control group.The myocardium showed increased uptake of 18F-FDG in the irradiated groups.The SUV of myocardium in 3-month,6-month and 12-month after radiation groups and control group were 5.90± 1.31,4.66±2.21,3.21±0.82 and 1.13±0.21,respectively (F=11.81,P＜0.05).The area with increased 18F-FDG uptake in the irradiated groups decreased progressively with the prolongation of irradiation time (F =195.74,P＜0.01).The reduction in myocardial perfusion and myocardial fibrosis were observed by CMR early at 6-month after irradiation.Compared with the control group,the 6-month and 12-month after radiation groups had increased end diastolic volume (EDV) and end systolic volume (ESV;F =15.479 and 16.908,both P＜0.01),and decreased left ventricular ejection fraction (LVEF;F=63.715,P＜0.01).The progressive aggravation of myocardial fibrosis was displayed in irradiated groups by Masson staining.The mitochondria degeneration,swelling and the count reduction in irradiated groups were observed by electron microscopy.Conclusions The increased 18F-FDG uptake in the irradiated myocardium may predict the risk of RIHD.18F-FDG PET/CT imaging can detect RIHD earlier than CMR.
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Objective@#To investigate the value of 18F-fluorodeoxyglucose (FDG) PET/CT imaging and cardiac MRI (CMR) in the diagnosis of radiation-induced heart disease (RIHD) in Beagle models.@*Methods@#Twenty-four normal male Beagle dogs (1-year old) were randomly divided into control group and irradiated groups (3-month, 6-month and 12-month after radiation). The left anterior myocardium of Beagle dogs in irradiated groups was irradiated locally with a single dose of 20 Gy X-ray. Cardiac 18F-FDG PET/CT imaging and CMR were performed on all dogs, and the mean standardized uptake value (SUVmean) and the area of lesions with increased 18F-FDG uptake were obtained. After imaging examinations were finished, dogs were sacrificed and their hearts were taken out to perform Masson staining and electron microcopy. One-way analysis of variance was used for data analysis.@*Results@#There was basically no uptake in myocardium in control group. The myocardium showed increased uptake of 18F-FDG in the irradiated groups. The SUVmean of myocardium in 3-month, 6-month and 12-month after radiation groups and control group were 5.90±1.31, 4.66±2.21, 3.21±0.82 and 1.13±0.21, respectively (F=11.81, P<0.05). The area with increased 18F-FDG uptake in the irradiated groups decreased progressively with the prolongation of irradiation time (F=195.74, P<0.01). The reduction in myocardial perfusion and myocardial fibrosis were observed by CMR early at 6-month after irradiation. Compared with the control group, the 6-month and 12-month after radiation groups had increased end diastolic volume (EDV) and end systolic volume (ESV; F=15.479 and 16.908, both P<0.01), and decreased left ventricular ejection fraction (LVEF; F=63.715, P<0.01). The progressive aggravation of myocardial fibrosis was displayed in irradiated groups by Masson staining. The mitochondria degeneration, swelling and the count reduction in irradiated groups were observed by electron microscopy.@*Conclusions@#The increased 18F-FDG uptake in the irradiated myocardium may predict the risk of RIHD. 18F-FDG PET/CT imaging can detect RIHD earlier than CMR.
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Objective:To establish the C57BL/6 mouse models of radiation-induced cardiopulmonary dysfunction.Methods:Twenty-four male C57BL/6 mice were randomly divided into the control and irradiation groups. Mice in the irradiation group were irradiated with 20 Gy electron beam and bred for 6 months after irradiation. Cardiac function was assessed using ultrasonography. The partial pressure of oxygen was detected by blood gas analysis. Cell apoptosis was observed by Tunel assay. Myocardial and pulmonary fibrosis was assessed by Masson staining.Results:The LVEF in the irradiation group was (68.60±10.92)%, significantly less compared with (81.75±8.79)% in the control group ( P< 0.01). The apoptotic index of heart in the irraiation group was (23.90±6.60)%, considerably higher than (3.25±3.38)% in the control group ( P< 0.01). The CVF of heart in the irradiation group was (15.42±5.72)%, significantly higher than (1.45±0.64)% in the control group ( P< 0.01). The PaO 2 level in the irradiation group was (86.10±7.60) mmHg, significantly lower compared with (107.16±9.01) mmHg in the control group ( P< 0.01). The apoptotic index of lung in the irradiation group was (27.90±8.94)%, significantly higher than (2.50±3.55)% in the control group ( P<0.01). The CVF of lung in the irradiation group was (17.76±5.77)%, remarkably higher than (2.50±3.55)% in the control group ( P< 0.01). Conclusion:Radiation can induce cardiopulmonary apotosis and fibrosis remodeling, which leads to cardiopulmonary dysfunction, suggesting the successful establishment of C57BL/6 mouse model of radiation-induced cardiopulmonary dysfunction.
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Objective To investigate the value of local myocardial blood flow and myocardial function parameters in monitoring the dynamic changes of radiation induced heart disease (RIHD) using 13NNH3 PET gated myocardial perfusion imaging(GMPI).Methods Six healthy male Beagle dogs underwent 13N-NH3 PET GMPI 1 week before irradiation and 3,6 and 12 months after irradiation in the anterior wall of the left ventricle with a single dose of 20 Gy.Global myocardial function parameters including left ventricular ejection fraction (LVEF),end-diastolic volume (EDV),end-systolic volume (ESV),and regional myocardial function parameters including wall motion (WM),wall thickening (WT),end-diastolic perfusion (EDP),end-systolic perfusion (ESP) before and after irradiation were compared by repeated measures analysis of variance and paired t test.Results There were no significant changes between EDV,ESV and LVEF at baseline and those at 3 months after irradiation.EDV at 6 months after irradiation still had no change,compared with baseline value and EDV at 3 months after irradiation,but ESV was increased and LVEF was decreased.Twelve months after irradiation,ESV was further expanded,LVEF was further reduced,and EDV began to increase (F values:20.974-177.846,all P＜0.05).Compared with the baseline,WM,WT,EDP and ESP were increased in 10％(2/20),20％(4/20),10％(2/20) and 15％(3/20) of myocardial segments at 3 months after irradiation (t values:14.446-672.315,all P＜0.05);those parameters were decreased in 15％(3/20),20％(4/20),15％(3/20) and 25％(5/20) of myocardial segments at 6 months after irradiation (t values:18.171-723.156,all P＜0.05),and were decreased in 35％(7/20),45％(9/20),40％(8/20) and 60％ (12/20) of myocardial segments at 12 months after irradiation (t values:14.783-711.259,all P＜0.05).Conclusions 13N-NH3 PET GMPI could be used to detect RIHD early and monitor the dynamic development of RIHD.Compared with the global left ventricular function parameters,regional myocardial function parameters (WM,WT,EDP and ESP) are more sensitive,which may be served as the early monitoring indicators for RIHD.
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Objective To evaluate the effect of the bladder scanner upon maintaining the consistency of bladder filling in cervical cancer patients during the intensity-modulated radiotherapy.Methods The bladder volume change of 20 patients diagnosed with cervical cancer throughout radiotherapy were retrospectively analyzed to determine the timing of introducing the bladder scanner. Ten patients undergoing cervical cancer radiotherapy were selected to analyze the consistency between the bladder volume measured by bladder scanner and cone-beam CT (CBCT).The changes of bladder volume before and after the intervention of bladder scanner were statistically compared. Results In total,100 CBCT images of 20 patients were retrospectively analyzed. Nonparametric test demonstrated that the bladder volume significantly differed compared with the planning volume ( P< 0. 05). Bland-Altman plot illustrated high consistency between the bladder volume measured by the bladder scanner and CBCT images with a mean difference of-6. 66 cm3 (95％CI: - 53. 1-39. 83 cm3 ). Paired-t test showed there was statistical difference between the bladder volume before intervention and the planning bladder volume (P= 0. 000).The bladder volume after intervention did not significantly differ from the planning bladder volume (P= 0. 745). Conclusions The bladder volume significantly varies throughout the treatment process. Bladder scanner should be utilized prior to treatment. The bladder volume measured by the portable bladder scanner is consistent with the planning bladder volume.
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Objective To investigate the protective effect of hydrogen-rich water on rat cognitive dysfunction induced by ionizing radiation.Methods A total of 20 SD rats were randomly divided into four groups with the ramdom number table method: control group(C),hydrogen-rich water group(HRW),irradiation group(IR)and hydrogen-rich water intervention group(HRW+IR),with 5 rats in each group.The spatial memory ability of rats was tested by a morris water maze.The expression of apoptosis-related genes was detected by real-time fluorescence quantitative PCR.The changes of glutathione(GSH),8-hydroxydeoxy guanosine(8-OHdG)and malondialdehyde(MDA)and SOD were also measured.Results The escape latency(F＝6.003,P＜0.05)and the swimming distances(F＝3.850,P＜0.05)of rats in four different groups had statistically significant differences.Compared with the IR group,the escape latency of the HRW+IR group was significantly decreased at 3,4,5 d after irradiation(P＜0.05),and the swimming distance of this group became much longer(P＜0.05).The levels of GSH,8-OHdG and MDA in these four groups had statistically significant differences(F＝6.450,5.033,4.113,P＜0.05).Compared with IR group,the concentration of GSH was increased(P＜0.05),but MDA and 8-OHdG decreased(P＜0.05)in the brain tissue of HRW+IR group,and the expressions of caspase-3,caspase-9 and bax genes were reduced(t＝2.956,3.087,5.246,P＜0.05),while the expression of bcl-2 gene was enhanced(t ＝-3.640,P ＜0.05)in the HRW+IR group.Conclusions Hydrogen-rich water attenuates the oxidative damage of ionizing radiation by neutralizing oxyhydrogen free radicals and thus protects brain from radiation damage.
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OBJECTIVE:To provide reference for the improvement of Chinese patent medicine instruction.METHODS:The outpatients were selected randomly from a Third Grade Class A hospital.A questionnaire survey was conducted on the attention degree of the outpatients to Chinese patent medicine instructions when taking medicine orally.The concern content label of patients in 221 Chinese patent medicine instructions were counted,analyzed and graded according to survey results.RESULTS:A total of 515 questionnaires were distributed,and 498 effective questionnaires were collected with effective recovery rate of 96.7％.The results of questionnaire survey showed that the highest concern from the patients was usage and dosage (92.4％),followed by attentions and taboos (88.0％,70.3％).The following items were drug interaction,pregnant and lactating women medication,children medication and the elderly medication (56.2％,46.4％,45.2％,42.4％).Among the description of medication methods (usage and dosage) in 221 Chinese patent medicine instructions,203 prescriptions clearly marked medication times (91.9％),160 clearly marked drug dosage (72.4％) and 36 clearly marked medication course (16.3％).In matters of taboos (attentions,taboos,pregnant and lactating women medication,children medication and the elderly medication),124 prescriptions clearly marked population taboos (56.1％),82 clearly marked symptom taboos (37.1％) and 71 clearly marked diet taboos (32.1％).According to the scoring statistics of 221 Chinese patent medicine instructions,there were 52 instructions with score of 6,followed by 47 instructions with score of 8;there were only 4 instructions with full score (12).CONCLUSIONS:At present,related contents of medication methods highly concerned by the patients are well marked in Chinese patent medicine instructions,especially its guidance is basically able to meet the requirements in respect of medication times.The related contents of medication taboos,which is next only to attention degree of medication methods by patients,is poorly marked.Its guidance remains to be improved.
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Objective To explore the feasibility to set the breast board support plate angle to 0° for breast cancer patient in the intensity modulated radiation therapy. Methods A total of 60 patients with breast cancer who received the simultaneous integrated boost intensity-modulated radiation therapy ( SIB-IMRT) after breast-conserving surgery were enrolled form Oct 2015 to Feb 2017. They were randomly divided into three groups that the angle of the breast board support plate was 12°, 7° and 0° respectively. The ipsilateral lung V20 , V5 , Dmean , the heart V10 , V30 , Dmean and the collimator angle were compared among three groups. In addition, the distribution of the setup error was analyzed and the group system error and random error were calculated. Results There were no statistically significant differences in the ipsilateral lung V20, V5, Dmean and the heart V10, V30, Dmean among the three groups(P >0. 05). The sum of the collimator angle and the angle of the support plate was about 13. 4° for each group. Only the setup error of z (vertical) direction was statistically different (χ2 =78. 32, P<0. 001) and the median of the 0° group was closest to the value 0 and the quartile spacing was the smallest. The absolute error of y ( longitudinal) , z directions was statistically different (χ2 =7. 63, 22. 61,P<0. 05). In the z direction, the absolute error was reduced as the angle of the support plate decreased and 0°group was the smallest. In the y direction, the absolute error at 12° was the smallest, but had little difference with that at 0°. Among three groups, the smallest system error of the x(lateral) direction and y direction was at 0°, while that of the z direction was at 12°. Conclusions To set the breast board support plate 0° is feasible. The angle of the support plate can be replaced by the collimator angle, while the setup error of z direction could be significantly reduced.
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Objective To explore the feasibility to set the breast board support plate angle to 0° for breast cancer patient in the intensity modulated radiation therapy. Methods A total of 60 patients with breast cancer who received the simultaneous integrated boost intensity-modulated radiation therapy ( SIB-IMRT) after breast-conserving surgery were enrolled form Oct 2015 to Feb 2017. They were randomly divided into three groups that the angle of the breast board support plate was 12°, 7° and 0° respectively. The ipsilateral lung V20 , V5 , Dmean , the heart V10 , V30 , Dmean and the collimator angle were compared among three groups. In addition, the distribution of the setup error was analyzed and the group system error and random error were calculated. Results There were no statistically significant differences in the ipsilateral lung V20, V5, Dmean and the heart V10, V30, Dmean among the three groups(P >0. 05). The sum of the collimator angle and the angle of the support plate was about 13. 4° for each group. Only the setup error of z (vertical) direction was statistically different (χ2 =78. 32, P<0. 001) and the median of the 0° group was closest to the value 0 and the quartile spacing was the smallest. The absolute error of y ( longitudinal) , z directions was statistically different (χ2 =7. 63, 22. 61,P<0. 05). In the z direction, the absolute error was reduced as the angle of the support plate decreased and 0°group was the smallest. In the y direction, the absolute error at 12° was the smallest, but had little difference with that at 0°. Among three groups, the smallest system error of the x(lateral) direction and y direction was at 0°, while that of the z direction was at 12°. Conclusions To set the breast board support plate 0° is feasible. The angle of the support plate can be replaced by the collimator angle, while the setup error of z direction could be significantly reduced.
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Objective To establish radiation-induced heart disease ( RIHD) Beagle models, in-vestigate the efficacy of 18 F-FDG PET/CT in the detection of RIHD and observe the pathological changes. Methods The ventricular anterior wall of 12 Beagle dogs were X-ray irradiated locally with a single dose of 20 Gy. 18 F-FDG PET/CT and echocardiography were performed at baseline and 3 months after radiation. ROI was drawn on the irradiation field and the non-irradiation field ( the posterior wall of left ventricle) to obtain the SUVmax . Then the SUVmax ratio of the irradiation field to the non-irradiation field ( INR) was cal-culated. The left ventricular function parameters before and after radiation were obtained by echocardio-graphy. Within 1 week after the imaging examinations were finished, the dogs were sacrificed, and hearts were taken out to perform pathological observation. Paired t test was used to analyze the data. Results High 18 F-FDG uptake in the irradiation field was shown 3 months after radiation. The average INRs before and after radiation were 0.99±0.15 and 2.54±0.43 respectively (t=7.021, P=0.001). No significant difference was ob-served on cardiac function parameters between baseline and 3 months after radiation( t values:from-1.253 to-0.786, all P>0.05) . The pathological results showed a few degenerated myocytes, increased thickness of myocardial vascular walls in irradiated myocardium. Conclusions 18 F-FDG PET/CT can detect early RIHD before abnormal cardiac function. Increased 18 F-FDG uptake in irradiated field may be related to myocardial ischemia which results from microvascular damage by radiation.
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OBJECTIVE: To determine the efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of radiation-induced myocardial damage in beagles by comparing two pre-scan preparation protocols as well as to determine the correlation between abnormal myocardial FDG uptake and pathological findings. MATERIALS AND METHODS: The anterior myocardium of 12 beagles received radiotherapy locally with a single X-ray dose of 20 Gy. 18F-FDG cardiac PET/CT was performed at baseline and 3 months after radiation. Twelve beagles underwent two protocols before PET/CT: 12 hours of fasting (12H-F), 12H-F followed by a high-fat diet (F-HFD). Regions of interest were drawn on the irradiation and the non-irradiation fields to obtain their maximal standardized uptake values (SUVmax). Then the ratio of the SUV of the irradiation to the non-irradiation fields (INR) was computed. Histopathological changes were identified by light and electron microscopy. RESULTS: Using the 12H-F protocol, the average INRs were 1.18 +/- 0.10 and 1.41 +/- 0.18 before and after irradiation, respectively (p = 0.021). Using the F-HFD protocol, the average INRs were 0.99 +/- 0.15 and 2.54 +/- 0.43, respectively (p < 0.001). High FDG uptake in irradiation field was detected in 33.3% (4/12) of 12H-F protocol and 83.3% (10/12) of F-HFD protocol in visual analysis, respectively (p = 0.031). The pathology of the irradiated myocardium showed obvious perivascular fibrosis and changes in mitochondrial vacuoles. CONCLUSION: High FDG uptake in an irradiated field may be related with radiation-induced myocardial damage resulting from microvascular damage and mitochondrial injury. An F-HFD preparation protocol used before obtaining PET/CT can improve the sensitivity of the detection of cardiotoxicity associated with radiotherapy.
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Animales , Perros , Masculino , Ayuno , Fluorodesoxiglucosa F18/metabolismo , Corazón/diagnóstico por imagen , Lesiones Cardíacas/diagnóstico por imagen , Miocardio/metabolismo , Tomografía de Emisión de Positrones/métodos , Traumatismos por Radiación/diagnóstico , Neoplasias Torácicas/radioterapia , Tomografía Computarizada por Rayos X/métodosRESUMEN
Objective To observe the effect of sodium dodecylbenzene sulfonate (SDBS) in killing Demodex in vitro and in the treatment of demodicidosis. Methods ① The experiment of in vitro killing Demodex with 1% and 2% SDBS was conducted. ② A clinical trial was carried out to evaluate the therapeutic effect in the treatment of demodicidosis with 2% SDBS and 2% metronidazole emulsion. Patients with demodicidosis were randomly divided into trial and control groups (31 cases each). They were treated with 2% SDBS ointment and 2% metronidazole ointment twice a day in the early morning and evening respectively for eight weeks consecutively. Inflammatory lesions of face, Demodex infestation and scores of erythema were measured to evaluate the effect before and after treatment. ③ Follow-up was carried out for two months to evaluate the effect and side-effects after 8 weeks' treatment. Results ① 2% SDBS killed all Demodex in vitro after 5h, there was significant difference between the 2% SDBS and 2% metronidazole (69