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Objective:To propose a machine learning-based markerless beam′s eye view (BEV) tumor tracking algorithm that can be applied to low-quality megavolt (MV) images with multileaf collimator (MLC)-induced occlusion and non-rigid deformation.Methods:This study processed the registration of MV images using the window template matching method and end-to-end unsupervised network Voxelmorph and verified the accuracy of the tumor tracking algorithm using dynamic chest models. Phantom QA plans were executed after the treatment offset was manually set on the accelerator, and 682 electronic portal imaging device (EPID) images obtained during the treatment were collected as fixed images. Moreover, the digitally reconstructed radiography (DRR) images corresponding to the portal angles in the planning system were collected as floating images for the study of target volume tracking. In addition, 533 pairs of EPID and DRR images of 21 lung tumor patients treated with radiotherapy were collected to conduct the study of tumor tracking and provide quantitative result of changes in tumor locations during the treatment. Image similarity was used for third-party validation of the algorithm.Results:The algorithm could process images with different degrees (10%-80%) of data missing and performed well in non-rigid registration of images with data missing. As shown by the phantom verification, 86.8% and 80% of the tracking errors were less than 3 mm and less than 2 mm, respectively, and the normalized mutual information (NMI) varied from 1.18 ± 0.02 to 1.20 ± 0.02 after registration ( t = -6.78, P = 0.001). The tumor motion of the clinical cases was dominated by translation, with an average displacement of 3.78 mm and a maximum displacement of 7.46 mm. The registration result of the cases showed the presence of non-rigid deformations, and the corresponding NMI varied from 1.21 ± 0.03 before registration to 1.22 ± 0.03 after registration ( t = -2.91, P = 0.001). Conclusions:The tumor tracking algorithm proposed in this study has reliable tracking accuracy and high robustness and can be used for non-invasive and real-time tumor tracking requiring no additional equipment and radiation dose.
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Introducción: Las leucodistrofias primarias son un grupo de trastornos hereditarios que afectan la sustancia blanca cerebral de forma predominante. El término leucodistrofias primarias unifica las enfermedades que afectan las células gliales con compromiso de la mielina y el axón de base genética. Es un grupo de entidades, más de 30 en la actualidad, en expansión gracias a los avances en resonancia magnética y en genética. Objetivo: Contribuir al conocimiento de esta rara enfermedad con énfasis en la utilidad de su conocimiento clínico y en los estudios de imágenes evolutivos para el diagnóstico. Presentación del caso: Paciente con macrocranea detectada por la familia a los tres meses de nacida, al inicio refirieron que la circunferencia cefálica creció rápidamente y a partir del segundo semestre de vida el crecimiento se hizo más lento. La valoración clínica al año de edad comprobó una discreta dificultad para el control cefálico, intentaba dar pasos con apoyo, lenguaje de 3 a 4 palabras y ninguna otra afectación del neurodesarrollo. Al examen físico, una circunferencia cefálica de 55 cm (por encima de dos desviaciones estándar para la edad cronológica y sexo). Conclusiones: La evolución clínica favorable conjuntamente con el patrón de la resonancia magnética cerebral, que inicialmente mostró afectación de la sustancia blanca compatible con leucodistrofia inespecífica y en estudios evolutivos detecta presencia de quistes subtemporales, permitieron el diagnóstico de esta rara enfermedad infantil. La paciente recibió tratamiento sintomático para la espasticidad, apoyo pedagógico y control de sus crisis epilépticas(AU)
Introduction: Primary leukodistrophies are a group of hereditary disorders that affect in a predominant way the white substance of the brain. The term ´´primary leukodistrophies´´ unifies the diseases that affect the glial cells compromising myelin and the genetic based axon. They are a group of entities, more tan 30 nowadays, which are expanding due to the advances in magnetic resonance and genetics. Objective: To contribute to the understanding of this rare disease with emphasis in the usefulness of its clinical knowledge and in the evolutive studies of images for diagnosis. Case presentation: Female patient with macrocranea detected by the family at 3 months old. At the beginning, the family referred that the cephalic circumference grew quickly and from the second semester of life growing process was slower. The clinical assessment at first year of life proved a discreet difficulty for cephalic control; the patient tried to do support footsteps, and had a language of 3 to 4 words without any other affectation in the neurodevelopment. In the physical examination, she presented a cephalic circumference of 55 cm (higher than the two stantard deviations for the cronological age and sex). Conclusiones: The clinical evolution was favorable jointly with the pattern of brain magnetic resonance that initially showed affectation in the white substance compatible with inespecific leukodistrophy and in the evolutive studies it was detected the presence of subtemporal cysts which allowed to diagnose this rare children disease. The patient received symptomatic treatment for spasticity, pedagogical support and control of the epileptic crisis(AU)
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Humans , Female , Infant , Leukodystrophy, Globoid Cell/diagnostic imagingABSTRACT
Objective To analyze the dosimetric and delivery efficiency differences between IMRT plans based on Halcyon and Trilogy Accelerator for left side breast cancer.Methods A total of 10 patients with left side breast cancer based on the Trilogy platform were retrospectively analyzed.For each patient,plan based on Halcyon was redesigned using Eclipse Version 15.1 TPS.In order to evaluate plan quality,dose coverage of target and dose to organs at risk,monitor unit efficiency,segment size and delivery time were compared.Results Halcyon treatment platform could meet the clinical objective.Dose distribution of the target volume had no significant difference with the Trilogy plans (P＞0.05).Volumes receiving 10 Gy,20 Gy and D of the left lung were significantly reduced(Z=-2.22--1.78,P＜0.05).V5 of heart for Halcyon and Trilogy was(27.80±7.66)％ and (23.18±8.19)％,respectively(Z=-0.71,P＜0.05),while D was (7.03± 1.8)Gy and(7.11±2.40)Gy,respectively(P＞0.05).Halcyon increased the monitor unit from 1 526.2±227.7 by Trilogy to 1 770.5±383.9(Z=-0.71,P＜0.05),but decreased the delivery time from (12.38± 1.49) min by Trilogy to (3.01 ±0.28) min (Z =-3.42,P＜ 0.05).Conclusion Halcyon treatment platform can meet the clinical requirements,reduce dose to normal tissue with high delivery efficiency.
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Objective To investigate the commissioning and testing of the Eclipse model of an Edge accelerator with high-definition muhi-leaf collimator (HD-MLC).Methods The percentage depth dose (PDD),profile,output factor measured by Razor and CC13 were statistically compared with the standard data.Penumbra,transmission factor (TF),leakage,concave-convex groove,accuracy of movement and dosimetry leaf gap (DLG) were measured with EBT3,electronic portal image device (EPID) and PTW SRS1000&SRS1500.The optimal DLG/TF was acquired when the γ pass rate of test cases was the highest.The point dose of regular fields,intensity-modulated radiation therapy (IMRT) and volume-modulated radiation therapy (VMAT) was verified with FC65-G.The planar dose of these case was verified with Octavius 4D and EBT3.Results The measured PDD data were consistent with the standard data.The measured penumbra of 3 cm and 4 cm square fields was smaller,whereas that of 6 cm square field was larger than the standard values.The left and right edge,field size,center of the field were distributed within the range of-1.0-0.4 mm、0.2-1.7 mm,-0.3-1.9 mm and-0.1-0.8 mm,respectively.The mean penumbra of the left and right MLC in different positions were (2.5±0.042) mm and (2.7±0.005) mm.The leakage of MLC was 0.009-0.016.The measured DLG/TF was 0.1861 cm/0.0116 and the optimal DLG/TF was 0.015 cm/0.014.The differences of point dose of all the test cases except the one which was in the low-dose area were within ±3％.Local and global γ pass rates of all IMRT were 79.81％-100％ and 96.3％-100％ (3％/3 mm),71.3％-98.9％ and 94.3％-99.8％ for VMAT cases.Conclusions This method can accurately test and commission the Eclipse treatment planning model of Edge Linac equipped with HD-MLC.
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Objective To compare the dosimetric and delivery efficiency between intensity-modulated radiation therapy (IMRT) plans based on Halcyon and Trilogy accelerator.Methods Clinical data of 12 patients with cervical cancer receiving Trilogy platform-based IMRT were retrospectively analyzed.The target area and organ at risk were introduced into the Eclipse version 15.1 TPS.The Halcyon-based IMRT was re-designed.The dose coverage of target area and organs at risk,monitor unit (MU) efficiency,delivery time and segment area and the differences between the proximal and distal segment area were statistically compared between two IMRT plans.Results The Halcyon treatment platform could meet the clinical objectives.Dose distribution of the target area was similar to that of the Trilogy plan (P＞O.05).The volumes in the bladder and rectum receiving 30 Gy and the volumes in the left femoral head receiving 20 Gy of Halcyon plan and the mean dose (D) of bladder,rectum and left femoral head were significantly lower compared with those of the Trilogy plan (P=0.001-0.043).The MUs of the Halcyon plan was 2 316.7± 209.7,significantly higher than 1 692.5± 259.5 of the Trilogy plan (P=0.000).The delivery time significantly differed between the Halcyon [(3.01±0.28) min] and Trilogy [(12.38± 1.49) min] (P=0.000).The average segment area of Halcyon plan for proximal and distal MLC was (43.7±32.5) cm2 and (28.8±25.4) cm2,the average segment area of Trilogy plan was (25.7±16.8) cm2,the ratio of the proximal and distal segment area was 1.73±0.43,ranging from 0.71 to 6.28.Conclusions Halcyon treatment platform can meet the clinical requirements and reduce the dosage coverage of normal tissues with better delivery efficiency.The ratio of proximal and distal segment areas should be considered during the plan design.
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Objective To verify the accuracy of multi-leave collimators (MLC) leaves position in intensity modulated radiation therapy (IMRT) using radiochromic films.Methods 7 medical electronic linear accelerators of Varian,Elekta or Siemens design were chosen.25 cm× 25 cm films were put on 30 cm×30 cm×3.0 cm homogeneous solid phantom and covered with a 2.0 cm thick of homogeneous solid phantom.The CT scanned images were transmitted to TPS for plan preparation.A 5 strip picket fence pattern was formed by MLC leaf,each 3 cm long and 0.6 cm wide,with 3.0 cm wide strip separation.At the maximum dose point,the SSD was 100 cm,with 250 MU per strip.After exposure,the films were transmitted to the dosimetry laboratory at IAEA for measurement and calculation.Results For 6 of 7 accelerators chosen,the differences of film-measured and TPS-planned MLC leaf position for every fence were within ± 0.5 mm as required by IAEA,and the other one not consistent with the requirements.The difference of film-measured MLC leaf position between each pair and all pair for 7 accelerators were within ± 0.5 mm,in line with IAEA's requirements.The differences of film-measured MLC leaf actual width were within 0.75 mm,as required by IAEA,for 6 accelerators and-0.8 mm for the other one,not consistent with the IAEA requirements.The standard deviations of film-measured MLC leaf actual width for all pairs for 6 accelerators were ＜0.3 mm,in line with IAEA requirements,but 0.4 mm for the other one,not consistent with IAEA requirements.Conclusions It is simple,fast and accurate to use radiochromic films for verification of the accuracy of MLC leaf position in IMRT.Therefore it is advisable to widely use radiochromic films in IMRT clinical practice.
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Objective To measure the positioning accuracy of multi-leaf collimators (MLC) leaves by using radiochromic films,with aim to providing data in support of IAEA's methodology validation.Methods The present study focused on 8 accelerators (Varian,Elekta and Siemens machines) at 6 hospitals in Henan province with highly skilled physicists.The 25 cm × 25 cm radiochromic films were put on 30 cm × 30 cm homogeneous solid phantoms and covered with a 2.0-cm-thick homogeneous solid phantom slabs.The CT-scanned images were transmitted to TPS for plan formulation.With 6 MV X-ray,MLC created 5 strip 3 cm × 0.6 cm picket fence field,each with 3.0 cm strip separation.The SSD was 100 cm at the maximum dose point,with a 250 MU to each strip.The irradiated radiochromic films were returned to IAEA for analysis within one week and compared with the values given by IAEA.Results The difference of film-measured and TPS-planned positions of MLC leaves for each strip picket fence should be within ± 0.5 mm as required by IAEA.For 7 of 8 accelerators selected,the differences of accurately measured MLC leaf positions were all within ±0.5 mm,which were in line with the IAEA requirements,with only other one being beyond-0.5 mm,not consistent with the IAEA requirements.The differences of film-measured actual widths between each pair and all pairs of leaves were within ±0.75 mm as required by IAEA for 7 accelerators,whereas the other one was outside ± 0.75 mm,not consistent with the IAEA requirements.The standard deviation of film-measured actual width of MCL leaf between each pair and all pairs for 7 accelerators were ≤ 0.3 mm as required by IAEA,whereas the other one was 0.5 mm,not consistent with IAEA requirements.Conclusions The MLC positioning accuracy of a few of medical accelerators in Henan is not qualified.It is of great significance to carry out regular quality examination as well as third-party verification to ensure precise delivery of radiotherapy.
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Objective To verify the leaf positioning accuracy of multi-leaf collimator (MLC) in intensity modulated radiation therapy (IMRT) by using radiochromic films to provide references for IMRT quality control.Methods Medical linear accelerators of different designs,owned by 7 first-class hospitals at grade-3 in Hubei,were selected for this verification study.Five strip picket fence pattern was created by treatment planning system (TPS).Each strip was 0.6 cm wide with a 3 cm strip separation.MLC leaf positions,positioning bias and opening widths were then measured with EBT2 radiochromic films.Results According to IAEA standards,the film-measured and TPS planned MLC leaf position difference was ±0.5 mm.The difference of MCL strip position of No.5 and No.7 accelerator was 0.7 and-1.0 mm,respectively,not in line with the IAEA standards.The difference of film-measured MLC leaf position between each pairs and all pairs of leaves of 7 accelerators were all within ± 0.5 mm,in line with the IAEA requirements.As required by IAEA,the difference of opening width of MLC leave of each pair relative to the averaged widths of all pairs should be within ±0.75 mm.The filem-measured values from 7 accelerators ranged from-0.6 to 0.5 mm,all in line with the IAEA standards.Standard deviation of opening width of all leaves were required to be within 0.3 mm.The measured values from 7 accelerators ranged from 0.1 to 0.2 mm,in line with the IAEA standard.Conclusions The use of EBT2 radiochromic films to verify MLC leaf positioning accuracy is an important means of quality control owing to its simplicity and high measurement accuracy.It is recommended for verification use at a large scale.
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Objective To measure the accuracy of multi-leaves collimator (MLC) leaves positions in intensity modulated radiation therapy (IMRT) for verification purpose.Methods Solid water homogeneous phantom with size of 30 cm× 30 cm was scanned by CT scanner.The scanned images were delivered to radiation therapy plan system (TPS) to formulate the therapy plan.The MLC leaves created 5 strips of exposure field,each 3 cm long and 0.6 cm wide.The strip-to-strip distance was 3 cm.With 6 MV X-rays,the SSD was 100 cm at the maximum dose point.The MU per strip was 250 MU.EBT2 radiochromic films each of 25 cm×25 cm were placed on the 30 cm×30 cm homogeneous solid phantom and covered with 1 cm thick solid phantom slabs for delivering of IMRT.Results For 7 of 8 accelerators,the differences of film-measured and TPS-planned MLC leaf position for every fence field were within ± 0.5 mm as required by IAEA,with only other one being-0.6 mm,not consistent with the IAEA requirements.The film-measured position difference between each pair and all pairs of leaves for 8 accelerators were all in line with IAEA's requirements.The film-measured actual width difference between each pair and all pairs of leaves was within ±0.75 mm as required by IAEA for 4 accelerators and outside ±0.75 mm for the other three,not consistent with the IAEA requirements.The standard deviation of film-measured actual width between each pair and all pairs of leaves for 6 accelerators were ≤ 0.3 mm,as required by IAEA,whereas ＞0.3 mm for the other two,not consistent with IAEA requirements.Conclusions The film dosimetric verification of IMRT is an important part of its quality assurance,featuring simple,reliable and highly accurate positioning and can meet measurement requirement.
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Objective To develop measurement methodology using film for the positioning accuracy of MLC leaves in IMRT.Methods The solid water phantom of 30 cm x 30 cm was scanned and the scanned images were transferred to TPS for treatment plan formulation.The five MLC strip picket fence pattern was formed by MLC leaves,each 3.0 cm long × 6.0 mm wide.The separation between strip and strip is 3.0 cm.SAD is 100 cm at dmax for 6 MV X-ray,with 250 MU per MLC strip.EBT2 radiochomic film was put on the phantom for delivery of IMRT,for each MLC strip.The present study focused on 30 accelerators of Varian,Elekta and Siemens designs at 27 hospitals with highly skilled physicists all over Jiangsu,Sichuan,Hubei and Henan provinces.The study was conducted in the same way as used in international multi-radiotherapy center (IMRC).The irradiated films were sent respectively to IAEA dosimetry laboratory and external audit group (EGA) of China for measurement,analysis and calculation.Results According to IAEA requirements,the differenc of film-measured and TPS-planned of MLC leaf position for each strip should be within ±0.5 mm.China had participated in the research of IMRC,with the result of 0.3,0.2,0.0,-0.1,and-0.2 mm,respectively.For 30 accelerators in four provinces involved in the study,the IAEA's verification results of MLC leaf position were within 0.6-1.0 mm for 5 accelerators and within ± 0.5 mm for other 25 ones.Whereas the verification results of EAG were within 0.6-1.0 mm for 6 accelerators and within ±0.5 mm for other 24 ones.According to IAEA requirements,the film-measured MLC leaf position deviation for each pair of leaves and average all pairs of leaves should be within ±0.5 mm.China had participated in IMRC's research,with the measured result being 0.04 mm.The verification result of EGA for 30 accelerators showed the measured MLC leaf position deviations were all ＜0.3 mm per strip,consistent with IAEA requirements.The IAEA's result showed the measured deviations of MLC leaf position for 29 accelerators were within ±0.5 mm,with only other one being-0.7 mm not consistent with the IAEA requirements.As required by IAEA,the difference of film-measured difference of MLC opening width should be within ±0.75 mm between each pair and average all pairs of leaves.China's result in research of IMRC showed the difference of minimum width to mean width was-0.2 mm whereas the difference of maximum width to mean width was 0.4 mm.For 30 accelerators involved in IAEA'verification study,the measured result shown that the difference between maximum and average of filmmeasured of MLC leaf width,and between minmum and average,were within ± 0.75 mm for 24 accelerators,in line with the IAEA requirements.For other 6 ones,the values were beyond ±0.75 mm,not in line with the IAEA requirements.For the verification result of EAG,the difference between maximum and average widths and between minmum and average widths for 25 accelerators were within ±0.75 mm as required by IAEA,whereas for other 5 ones the value were beyond ±0.75 mm,not consistent with IAEA requirements.The standard deviation of film-measured MLC opening width between each pair and average all pairs should be within 0.3 mm as required by IAEA.China's IMRC result was 0.12 mm.The verification result of IAEA shown the standard deviation of MLC opening position were ＜0.3 mm for 26 accelerators and ＞ 0.3 mm for other 4 accelerators.EAG verification result were the same as IAEA result.Conclusions The method using radiochromic film for measuring accuracy of MLC leaf position is convenient and practicable as a quality audit.It is suitable for quality verification in medical institutions owing to easy to post and repeated measurements.
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Objective:To investigate the effect of endothelin-1 (ET-1) on the expression of phosphorylated myosin light chain Ⅱ(p-MLCⅡ)and myosin light chain Ⅱ(MLCⅡ)protein in rat hepatic stellate cells HSC-T6 and explore the intervention effect of Danggui Shaoyao San(DSS)drug-containing serum. Method:After HSC-T6 cells were seeded, DMEM and blank rat serum with final concentrations of 2.5%, 5%, 10%, 15% and 20% were added to each well. The viability of HSC-T6 cells was determined by methyl thiazolyl tetrazolium(MTT) assay to screen the suitable serum concentration range. The cells were divided into blank serum control group (5%, 10%, 15%) and DSS drug-containing serum group (5%, 10%, 15%). ELISA was used to detect the content of ET-1 in cell culture supernatant under basic state. The cells were divided into blank serum control group (10%), DSS drug-containing serum low (5%), medium (10%) and high dose (15%) groups. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to detect the level of ET-1 mRNA in cell culture supernatant under basic state. The cells were divided into blank serum control group (10%), model group (10%), DSS drug-containing serum low (5%), medium (10%), high dose (15%) groups and Y-27632 inhibitor group (100 μmol·L-1). Except the blank serum control group, the other groups all received 10 nmol·L-1 ET-1 to induce HSC-T6 cells. Western blot was used to detect the expression of p-MLCⅡ and MLCⅡ in HSC-T6 cells induced by ET-1. Result:Serum concentrations of 5%, 10% and 15% were used as drug-containing serum concentrations. As compared with the blank serum control group, the DSS drug-containing serum group significantly reduced the relative content of ET-1 and ET-1 mRNA in the basic state (PPPPPConclusion:DSS drug-containing serum may down-regulate the expression of p-MLCⅡ and MLCⅡ by down-regulating the content of ET-1 and inhibiting the autocrine of ET-1.
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MSC transplantation has been explored as a new clinical approach to stem cell-based therapies for bone diseases in regenerative medicine due to their osteogenic capability. However, only a small population of implanted MSC could successfully reach the injured areas. Therefore, enhancing MSC migration could be a beneficial strategy to improve the therapeutic potential of cell transplantation. Catharmus tinctorius volatile oil (CTVO) was found to facilitate MSC migration. Further exploration of the underlying molecular mechanism participating in the pro-migratory ability may provide a novel strategy to improve MSC transplantation efficacy. This study indicated that CTVO promotes MSC migration through enhancing ROCK2 mRNA and protein expressions. MSC migration induced by CTVO was blunted by ROCK2 inhibitor, which also decreased myosin light chain (MLC) phosphorylation. Meanwhile, the siRNA for ROCK2 inhibited the effect of CTVO on MSC migration ability and attenuated MLC phosphorylation, suggesting that CTVO may promote BMSC migration via the ROCK2/MLC signaling. Taken together, this study indicates that C. tinctorius volatile oil could enhance MSC migration via ROCK2/MLC signaling in vitro. C. tinctorius volatile oil-targeted therapy could be a beneficial strategy to improve the therapeutic potential of cell transplantation for bone diseases in regenerative medicine.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Jiaji" (EX-B 2) on limb locomotor function and expression of Ras homolog gene family member A (RhoA), Rho-associated kinase Ⅱ (ROCK Ⅱ) and myosin light chain (MLC) proteins in the anterior horn of spinal cord in acute spinal cord injury (ASCI) rats, so as to explore its mechanisms under-lying improvement of SCI-induced limb locomotor dysfunction. METHODS: Forty-eight female Wistar rats were randomly divided into sham operation (sham), ASCI model (model), EA EX-B 2 (EA) and ROCK inhibitor (Fasudil) groups which were further divided into 14 d and 28 d subgroups (n=6 in each). The ASCI model was made by using weight drop striking method. Three hours after modeling, EA (100 Hz, 0.4, 0.6 mA) was applied to EX-B 2 (T 9, T 11) for 30 min, once daily for 14 d and 28 d, respectively. The ROCK inhibitor (hydrochloride Fasudil, 10 mg/kg) was administrated by intraperitoneal injection immediately after modeling, once a day, continuously for 14 d or 28 d. The expression of RhoA, ROCK Ⅱ and MLC proteins in the spinal cord anterior horn tissue (T 10) was detected by immunohistochemistry. The rats' hindlimb locomotor function was assessed according to Basso, Beattie and Bresnahan (BBB) locomotor rating scale (21-points). RESULTS: After ASCI, the BBB scores were significantly lower in the model group than in the sham group on day 14 and 28 (P<0.05), and obviously higher in the EA and inhibitor groups than in the model group (P<0.05), suggesting an improvement of the hindlimb locomotor function after EA intervention or suppression of ROCK. Immunohistochemical results indicated that the numbers of RhoA, ROCK Ⅱ and MLC immune-reaction positive cells in the anterior horn of spinal cord were significantly more in the model group than in the sham group (P<0.05), and remarkably decreased in both EA and inhibitor groups on day 14 and 28 relevant to the model group (P<0.05). The therapeutic effects of EA were markedly weaker than those of inhibitor Fasudil in up-regulating BBB score and down-regulating the number of RhoA, ROCK Ⅱ and MLC positive cells (P<0.05). CONCLUSION: EA of EX-B 2 can improve the hindlimb locomotor function in ASCI rats, which may be associated with its effect in down-regulating the expression of RhoA, ROCK Ⅱ and MLC proteins (i.e., inhibiting the RhoA/ROCK signaling pathway) in the anterior horn of spinal cord.
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Objective To analyze the clinical characteristics and genetic variation of megalencephalic leu-koencephalopathy with subcortical cysts(MCL),then to explore the genetic characteristics so as to help families by pro-viding genetic counseling. Methods The clinical data of the children and their family members were collected,and the peripheral blood DNA of the children and family members were extracted. Then,the MLC1 gene mutation in the children was detected by using the target sequence capture high-throughput sequencing technology and Sanger sequencing tech-nology. Results (1)MCL often presented abnormal head circumference in infants as the first symptom. The main clini-cal manifestations were hypoevolutism in motor development,retrogression of early school age,then the movement disor-der progressed and finally paralyzed;epilepsy was common in early childhood;head magnetic resonance imaging showed white matter in bilateral cerebral hemisphere diffusing abnormal signal with temporal lobe cystic change in the early stage,and then showed brain atrophy. (2)The gene results showed that the 2 girls with MLC had both c. 368C >T (p. Thr123Ile)and c. 353C > T (p. Thr118Met)complex heterozygous variation,which existed in the MLC1 gene. The girls′ father and a sister carried c. 368C > T (p. Thr123Ile),while the mother carried c. 353C > T (p. Thr118Met) heterozygous variation,all of whom were normal phenotypes. Conclusions MCL is one cause of hypoevolutism in motor development in children and abnormal head circumference of infants is usually the first symptom. The MLC1 gene c. 368C> T(p. Thr123Ile)is a pathogenic mutation for MLC,and may be another new pa-thogenic mutation.
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BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare inherited disorder characterized by infantile-onset macrocephaly, slow neurologic deterioration, and seizures. Mutations in the causative gene, MLC1, are found in approximately 75% of patients and are inherited in an autosomal recessive manner. We analyzed MLC1 mutations in five unrelated Korean patients with MLC. METHODS: Direct Sanger sequencing was used to identify MLC1 mutations. A founder effect of the p.Ala275Asp variant was demonstrated by haplotype analysis using single-nucleotide polymorphic (SNP) markers. Multiple ligation-dependent probe amplification (MLPA) and comparative genomic hybridization plus SNP array were used to detect exonic deletions or uniparental disomy (UPD). RESULTS: The most prevalent pathogenic variant was c.824C>A (p.Ala275Asp) found in 7/10 (70%) alleles. Two pathogenic frameshift variants were found: c.135delC (p.Cys46Alafs*12) and c.337_353delinsG (p.Ile113Glyfs*4). Haplotype analysis suggested that the Korean patients with MLC harbored a founder mutation in p.Ala275Asp. The p.(Ile113Glyfs*4) was identified in a homozygous state, and a family study revealed that only the mother was heterozygous for this variant. Further analysis of MLPA and SNP arrays for this patient demonstrated loss of heterozygosity of chromosome 22 without any deletion, indicating UPD. The maternal origin of both chromosomes 22 was demonstrated by haplotype analysis. CONCLUSIONS: This study is the first to describe the mutational spectrum of Korean patients with MLC, demonstrating a founder effect of the p.Ala275Asp variant. This study also broadens our understanding of the mutational spectrum of MLC1 by demonstrating a homozygous p.(Ile113Glyfs*4) variant resulting from UPD of chromosome 22.
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Humans , Alleles , Chromosomes, Human, Pair 22 , Comparative Genomic Hybridization , Exons , Founder Effect , Haplotypes , Leukoencephalopathies , Loss of Heterozygosity , Megalencephaly , Mothers , Seizures , Uniparental DisomyABSTRACT
Objective:To verify the dose of static and dynamic intensity modulated radiotherapy (IMRT) through 2-dimension ionization chamber matrix after external electrically-driven multi-leaf collimator (MLC) was installed in KB1800 medical linear accelerator. Methods: 40 patients who need receive IMRT were divided into static IMRT group (20cases) and dynamic IMRT group (20cases) as the random number table. The ionization chamber was applied to implement scale dose, and solid water and 2-D ionization chamber matrix was applied to verify dose. Besides, the feasibility of static and dynamic IMRT were compared and researched.Results: The verification results of plane dosage of static IMRT plan and dynamic IMRT plan showed that the passing rates both of them were above 90.0%, and the verification of intensity modulated dosimetry of medical electric linear accelerator KB1800 with external electric MLC was consistent with standard.Conclusion:After the external electrically-driven MLC is installed on the accelerator, the dosage of IMRT can achieve the verification standard, and it can be applied to clinical treatment and can satisfy the requirement of clinical radiotherapy.
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Objective:To verify the dose of static and dynamic intensity modulated radiotherapy (IMRT) through 2-dimension ionization chamber matrix after external electrically-driven multi-leaf collimator (MLC) was installed in KB1800 medical linear accelerator. Methods: 40 patients who need receive IMRT were divided into static IMRT group (20cases) and dynamic IMRT group (20cases) as the random number table. The ionization chamber was applied to implement scale dose, and solid water and 2-D ionization chamber matrix was applied to verify dose. Besides, the feasibility of static and dynamic IMRT were compared and researched.Results: The verification results of plane dosage of static IMRT plan and dynamic IMRT plan showed that the passing rates both of them were above 90.0%, and the verification of intensity modulated dosimetry of medical electric linear accelerator KB1800 with external electric MLC was consistent with standard.Conclusion:After the external electrically-driven MLC is installed on the accelerator, the dosage of IMRT can achieve the verification standard, and it can be applied to clinical treatment and can satisfy the requirement of clinical radiotherapy.
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Aim To investigate the effects of Sanjie Zhentong capsule on cultured mouse myometrial cell contraction induced by prostaglandin F2α( PGF2α) , and to elucidate the mechanism of Sanjie Zhentong capsule in treating dysmenorrheal. Methods Primary mouse myometrial cells were cultured and identified. Intracel-lular calcium ( [ Ca2+] i ) was monitored under a Flex-Station 3 Benchtop Multi-Modo Microplate Reader u-sing Calcium 6-QF. Myometrial cells were labeled to observe the changes of contraction. The expressions of calmodulin ( CaM ) , myosin light chain kinase ( ML-CK) , myosin light chain phosphorylation( p-MLC20 ) in mouse uterine smooth muscle cells ( USMCs ) were determined by immunofluorescence. Results Sanjie Zhentong capsule suppressed the intracellular[Ca2 + ]i inflow and reduced the areas of myometrial cells induced by PGF2α. Then it significantly decreased CaM and p-MLC20 levels. Conclusion Our results indicate that Sanjie Zhentong capsule has inhibitory effect on dysmenorrheal induced by PGF2α. Furthermore,its major mechanism may be related with the regulation of intracellular[ Ca2 + ]i inflow and the levels of CaM and p- MLC20.
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Objective: In this study, we examined whether Danhong Injection (DHI) exerted a relaxation effect in vascular smooth muscle cells (A7r5) in co-culture system by human umbilical vein endothelial cells (Ea.Hy926) and studied its mechanisms. Methods: First of all, Western blotting assay was carried out to quantify the protein expression of MLC and P-MLC in A7r5 cells. Secondly, calcium assay kit was used to detect the changes in intracellular calcium while the changes of CaM mRNA expression were subsequently detected by RT-PCR. MTT assay was used to detect the effect of DHI in proliferation of A7r5 cell, which is induced by PDGF-BB. Finally, the co-culture system of EA.Hy926 and A7r5 cells was constructed by a Transwell. After the treatment of Hy926 cells with DHI for co-culture system, the protein expression of MLC and P-MLC in A7r5 cells in co-culture system was also quantified by Western blotting. Cell-based ELISA was used to observe the cAMP generation in A7r5 cells. Results: DHI (10 μL/mL) contributed to the decrease of the ratio of P-MLC/MLC (P < 0.05) and CaM mRNA expression (P < 0.01) in A7r5 cells, which are cultured individually, but had no significant effect in intracellular calcium concentration and the expression of MLC proteins. In co-culture system, DHI (10 μL/mL) could still decrease the ratio of P-MLC/MLC (P < 0.05) and increase the secretion of cAMP (P < 0.01) in A7r5 cells. In addition, DHI contributed to suppress the proliferation of A7r5 cells which were induced by the PDGF-BB (P < 0.01). Conclusion: DHI can directly relax vascular smooth muscle cells by reducing the ratio of P-MLC/MLC and the expression of CaM mRNA, meanwhile indirectly relaxing the vascular smooth muscle cells in co-culture system by promoting the secretion of cAMP which is increased by vasodilatory factors in endothelial cells.
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Objective To investigate muli-leaf collimator (MLC)-defined small field output factors calculated by the treatment planning system (TPS), and to study the measuring method of small field output factors verified by 0.015 cc PinPoint ionization chamber.Methods Eight medical accelerators for intensity-modulated radiation therapy (IMRT) were investigated in Henan province, and TPS-calculated output factors for various small fields (6 cm ×6 cm,4 cm ×4 cm,3 cm ×3 cm and 2 cm ×2 cm) were compared with published values recommended by IAEA.If the relative deviation was more than ± 3％ for the 2 cm ×2 cm field size and ±2％ for the fields of 6 cm ×6 cm, 4 cm ×4 cm and 3 cm ×3 cm, which was beyond the scope of IAEA allowed, the output factors will be measured and verified using 0.015 cc PinPoint ionization chamber and Unidos electrometer.Results TPS-calculated small field output factors for eight medical accelerators were compared with published values.The relative deviation of small field output factors for five pieces of equipment, which accounted for 62.5％ of the total, met the IAEA's requirement, while the other three, which accounted for 37.5％ of the total, did not.After measuring with PinPoint ionization chamber, the results from only three pieces of equipment met minimum IAEA's requirement.Conclusions MLC-defined small field output factors calculated by TPS for some medical accelerators in Henan need to be measured and corrected using micro-ionization chamber, and the measured values could be taken as the basis of radiation treatment planning.