Objective:To establish a radiotherapy treatment planning process of high ventilation functional lung avoided (HVFLA) for thoracic tumors based on 4D-CT lung ventilation functional images and determine the treatment planning strategy of HVFLA radiotherapy, and so as to provide support for the clinical trials of HVFLA radiotherapy in thoracic cancer patients.Methods:A deep learning-based 4D-CT lung ventilation functional imaging model was established and integrated into the radiotherapy treatment planning process. Furthermore, ten thoracic cancer patients with 4D-CT simulation positioning were retrospectively enrolled in this study. The established model was used to obtain the 4D-CT lung ventilation functional imaging for each patient. According to the relative value of lung ventilation, the lung ventilation areas are equally segmented into high, medium and low lung ventilation and then imported them into Pinnacle 3 treatment planning system. According to the prescription dose of target and dose constraints of organ at risks (OARs), the clinical and HVFLA treatment plans were designed for each patient using volumetric modulated radiotherapy technique, and each plan should meet the clinical requirements and adding dose constraints of high ventilation functional lung for HVFLA plan. The dosimetric indexes of the target, OARs (lungs, heart and cord) and high functional lung (HFL) were used to evaluated the plan quality. The dosimetric indexes included D2, D98 and mean dose of target, V5, V10, V20, V30 and mean dose of lungs and HFL, V30, V40 and mean dose of heart, and D1 cm 3 of cord. Paired samples t-test was used for statistical analysis of the two groups of plans. Results:The target and OARs of the clinical plan and HVFLA plan meet the clinical requirements. The HVFLA plan resulted in a statistically significant reduction in the mean dose, V5, V10, V20, and V30 of the high functional lung by 1.2 Gy, 5.9%, 4.2%, 2.6%, and 2.3%, respectively ( t=-8.07, 4.02, -6.02, -7.06, -6.77, P<0.05). There was no statistical difference in the dosimetric indexes of lungs, heart and cord. Conclusions:We established the treatment planning process of HVFLA radiotherapy based on 4D-CT lung ventilation functional images. The HVFLA plan can effectively reduce the dose of HFL, while the doses of lungs, heart and cord had no significant difference compared with the clinical plan. The strategy of HVFLA radiotherapy planning is feasible to provide support for the implementation of HVFLA radiotherapy in thoracic cancer patients.

Objective:To verify the feasibility of using Elekta accelerated go live (AGL) standard process for the acceptance of multiple accelerators.Methods:The beams of three accelerators were adjusted by PTW Beamscan three-dimensional water tank to reach the AGL standard. Dose verification was performed for three accelerators that met AGL standards. A simple field test example from Cancer Hospital Chinese Academy of Medical Sciences was used to compare the MapCheck 3 surface dose measurement results with the surface dose calculated by the same accelerator model. Images of 10 patients including head and neck, esophagus, breast, lung and rectum were randomly selected. volumetric-modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) treatment techniques were used for planning design, and the measured dose of ArcCheck was compared with the planned dose calculated by the same accelerator model. One-way ANOVA was used to statistically analyze the passing rates of two-dimensional and three-dimensional dose verification.Results:The 6 MV X-ray percentage depth dose at 10 cm underwater (PDD 10) of three accelerators was 67.45%, 67.36%, 67.47%, and the maximum deviation between the three accelerators was 0.11%. The 6 MV flattenting filter free (FFF) mode X-ray PDD 10 was 67.33%, 67.20%, 67.20%, and the maximum deviation between the three accelerators was 0.13%. All required discrete point doses on each energy 30 cm×30 cm Profile spindle of the three accelerator X-rays deviated less than ±1% from the standard data. Absolute γ analysis was performed on the results of MapCheck 3 two-dimensional dose matrix validation. Under the 10% threshold of 2 mm/3% standard, the average passing rate of the test cases in Cancer Hospital Chinese Academy of Medical Sciences was above 99%, and the difference was not statistically significant ( P>0.05). Absolute γ analysis was performed on the ArcCheck verification results. Under the 10% threshold, the pass rate of 2 mm/3% was all above 95%, the maximum average passing rate of the three accelerators with different energy and different treatment techniques was 0.28% (6 MV, VMAT), 0.19%(6 MV FFF, VMAT), 0.56% (6 MV, IMRT) and 0.05% (6 MV FFF, IMRT), and the difference was not statistically significant ( P>0.05). Conclusion:Compared with traditional accelerator acceptance process, the acceptance time of each accelerator is shortened by 4-6 weeks by using the AGL standard process, and the radiotherapy plan of patients can be interchangeably executed among different accelerators.

ObjectiveTo investigate the mechanism of Huazhuo Jiedu Huoxue Tongluo prescription in alleviating cerebral ischemia-reperfusion injury via regulating nerve cell autophagy based on c-Jun N-terminal kinase（JNK）signaling pathway . MethodSixty SD rats were randomly divided into 6 groups： sham group， middle cerebral artery occlusion/reperfusion （MCAO/R） group （model group）， Huazhuo Jiedu Huoxue Tongluo prescription group ［traditional Chinese medicine （TCM） group（25.0 g·kg^-1）］， JNK inhibitor SP600125 （SP） group（5 mg·kg^-1）， TCM+SP group and JNK agonist Anisomycin （Ani） group（15 mg·kg^-1）. After 24 h of modeling， TCM group and TCM+SP group were given TCM decoction （ig） for 3 consecutive days， and the other groups were given equal volume of normal saline （ig）. Neurological deficit was evaluated by neurological function score and cerebral infarct volume was determined by 2，3，5-triphenyltetrazole chloride （TTC） staining. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the structural changes of brain tissue and the damage of neurons， respectively. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） was performed to detect cell apoptosis. The ultrastructure of autophagosomes was observed by transmission electron microscope. Western blot was employed to detect the protein expressions of microtubule-associated protein 1 light chain 3A/B （LC3A/B）， autophagy related 5 （Atg5）， the ortholog of yeast Atg6 （Beclin1）， p62， B-cell lymphoma 2 （Bcl-2）， JNK， phosphorylated （p）-JNK and c-Jun in brain tissue. The mRNA expressions of LC3A/B， Beclin1， p62， Atg5， Bcl-2， JNK and c-Jun were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the sham group， the model group had elevated neurological deficit score （P<0.05）， enlarged cerebral infarct volume （P<0.05）and typical infarction manifestations formed in hippocampal region and its surrounding brain tissue. In addition， there were a large number of neuronal cell degeneration， necrosis， liquefaction， nucleus pyknosis and deep staining， and inflammatory cell infiltration in the cortex in the model group， and severe swelling of mitochondria， lysosomes， autophagosomes and autophagolysosomes were clearly seen under electron microscope. TUNEL positive cells were increased （P<0.05）， and cell apoptosis was severe. The nuclear membrane and nucleolus of neurons in brain tissue were blurred with discontinuous processes， and Nissl bodies in cytoplasm were stained light with reduced number. Western blot revealed that the model group had up-regulated protein expressions of LC3A/B， Beclin1， Atg5， JNK， p-JNK and c-Jun in brain tissue （P<0.05）， while down-regulated protein expressions of p62 and Bcl-2 （P<0.05）as compared with the sham group. Real-time PCR indicated that the mRNA expressions of LC3A/B， Beclin1， Atg5， JNK and c-Jun in the model group were higher （P<0.05） while the mRNA expressions of p62 and Bcl-2 were lower （P<0.05） than those in the sham group. Compared with the conditions in model group， the neurological deficit scores of TCM， SP and TCM+SP groups were lowered （P<0.05）， and the cerebral infarct volume was reduced （P<0.05）， with improved pathological status of brain tissue， especially in the TCM group. Furthermore， there were abundant and basically normal mitochondrial cristae， slightly dilated endoplasmic reticulum， slightly swollen golgi apparatus， slightly fused nuclear membrane， and few visible lysosomes， autophagosomes and autophagolysosomes. TUNEL positive cells were decreased （P<0.05）， displaying reduced apoptosis， especially in the TCM group. The nucleolus and nuclear membrane of neurons in brain tissue were discernible， and Nissl bodies in cytoplasm was reduced to a certain degree as compared with those in the model group. Western blot showed a decrease in the protein expressions of LC3A/B， Beclin1， Atg5， JNK， p-JNK and c-Jun in the TCM group ，the SP group，and the TCM+SP group（P<0.05），while an increase in the protein expressions of p62 in the TCM group and SP group（P<0.05），and an increase in the protein expressions of Bcl-2 in the TCM group and TCM+SP group. By Real-time PCR， the mRNA expressions of LC3A， LC3B， Beclin1， Atg5， JNK and c-Jun had a down-regulation（P<0.05） while the mRNA expression of p62 a up-regulation in the TCM group ，the SP group，and the TCM+SP group（P<0.05），and the mRNA expression of Bcl-2 a up-regulation in the TCM group and the TCM+SP group（P<0.05）.Scores of the Ani group were raised （P<0.05）， and infarct volume was increased significantly， with aggravated neuronal cell necrosis and obvious inflammatory infiltration. Moreover， there were neuronal nuclear membrane fusion with abnormal protrusion， increased heterochromatin aggregation in edge， severe mitochondrial swelling， endoplasmic reticulum expansion， increased lysosomes， increased intracytoplasmic vesicles， and visible autophagosomes and autophagolysosomes. TUNEL positive cells were increased （P<0.05）， representing severe apoptosis. The number of Nissl bodies dropped with light staining， and the nucleolus and nuclear membrane were blurred. Real-time PCR found that the mNRA expressions of Atg5， c-Jun， JNK were up-regulated （P<0.05），while Beclin1， p62， Bcl-2 were were down-regulated in the Ani group （P<0.05）. Compared with the TCM group and SP group，the protein expressions of LC3A/B， Beclin1， Atg5， JNK， p-JNK， c-Jun were decreased，and p62， Bcl-2 were increased in the Ani group（P<0.05）. Compared with the TCM group，the mRNA expressions of JNK mRNA had a down-regulation in the SP group and TCM+SP group，while LC3A， LC3B， Atg5， c-Jun， JNK had an up-regulation（P<0.05） and Bcl-2 had a down-regulation in the Ani group（P<0.05）. Compared with the SP group，the mRNA expressions of Atg5， c-Jun， JNK had an up-regulation（P<0.05）， and Beclin1， p62， Bcl-2 had a down-regulation in the Ani group（P<0.05）. ConclusionHuazhuo Jiedu Huoxue Tongluo prescription significantly up-regulates the protein and mRNA expressions of LC3A/B， Beclin1， Atg5， JNK， p-JNK and c-Jun， and down-regulates the protein and mRNA expressions of p62 and Bcl-2， suggesting that the prescription can inhibit autophagy through JNK signaling pathway to reduce ischemia/reperfusion injury in rats.

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Objective:To introduce the clinical dosimetry commissioning methods and results of the 1.5 T MR-linac.Methods:In May, 2019, an Elekta Unity 1.5 T MR-linac was installed in Cancer Hospital, Chinese Academy of Medical Sciences and dosimetry commissioning was performed with magnetic field compatible measuring instruments. Commissioning items include absolute dose calibration, data acquisition and planning system model verification.Results:Absolute dose calibration in magnetic field should be corrected by magnetic field correction factor. The standard output dose of Unity was 87 cGy. Gamma analysis (3%/2 mm) was performed on the beam collection data and the planning system calculation data. The average pass rate of dose verification of standard field test cases was 96.41%, and the TG119 test case was 98.24%. The IROC end to end test case was 97.5%(7%/4 mm).Conclusions:The planning system model and the beam collection data have good consistency. The dose verification results of the standard field and TG119 test cases meet the general tolerance limit requirements of the AAPM TG218 report, and the verification results of the IROC end-to-end test cases meet the IROC center standards.

ObjectiveTo study the effect of Huazhuo Jiedu Huoxue Tongluo （HJHT） prescription on the intestinal flora in rats with cerebral ischemia-reperfusion injury， and to explore the mechanism of Chinese medicinal prescription regulating intestinal flora to restore the balance of brain-gut axis. MethodFifty male SPF SD rats were randomly assigned into sham group， model group， high-dose HJHT group （25.0 g·kg^-1）， medium-dose HJHT group （12.5 g·kg^-1）， and low-dose HJHT group （6.25 g·kg^-1）， with 10 rats in each group. The rat model of permanent middle cerebral artery infarction was established according to Longa method and previous research experience， and reperfusion was performed 2 h after ischemia. The recovery of neurological function deficit and the percentage of cerebral infarction area were detected 72 h after administration. Real-time PCR was performed to detect the mRNA levels of Occludin and zonula occludens-1 （ZO-1） in rat colon. Hematoxylin-eosin （HE） staining was conducted to reveal the intestinal damage. The feces of 6 rats in each group were collected for 16S rRNA sequencing. The expression of Treg and Th17 in intestinal tissue， peripheral blood， and brain tissue were detected. ResultCompared with the sham group， the model group showed obvious neurological deficit （P<0.05） and large cerebral infarction area （P<0.05）. High-dose and medium-doses HJHT alleviated the symptoms of neurological impairment （P<0.05） and reduce the cerebral infarction area （P<0.05） compared with the model group. Compared with the sham group， the model group showed destroyed structure of colonic mucosa and incomplete epithelial cells and goblet cells， while high-dose and medium-doses HJHT alleviated such changes. The mRNA levels of Occludin and ZO-1 in the model group were lower than those in the sham group （P<0.05），and the high-dose HJHT groups were higher than the model group （P<0.05）. The intestinal flora structure was significantly different between the model group and the sham group while similar between the high-dose HJHT group and sham group. Compared with the sham group， the model group showed down-regulated expression of Treg and up-regulated expression of Th17 in the intestinal tissue， peripheral blood， and brain tissue， and high-dose and medium-dose HJHT alleviated the changes in the expression of Treg and Th17 in the model group （P<0.05）. ConclusionHuazhuo Jiedu Huoxue Tongluo prescription may improve the permeability of intestinal wall by adjusting the abundance and diversity of intestinal microorganisms to reduce the migration of intestinal Th17 cells toward the ischemic lateral brain tissue， mitigate the inflammatory response， and thus alleviate the cerebral ischemia-reperfusion injury in rats.

BACKGROUND: Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). METHODS: The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. RESULTS: The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. CONCLUSION Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.
Lipid Metabolism/genetics* ; Mendelian Randomization Analysis ; Thyroid Function Tests ; Thyroid Gland ; Thyrotropin ; Thyroxine ; Triiodothyronine

Objective:To evaluate the effect of fast cone beam CT (CBCT) scan mode on image quality and registration results, and to establish the scanning pre-settings for fast CBCT.Methods:Three scanning modes were utilized to the CBCT phantom, and the registration accuracy and image quality were quantitatively evaluated. The correlation and consistency of measurement results under different scanning modes were further verified by 278 sets of CBCT data from 33 clinical tumor patients.Results:The maximum deviation between the measurement results of three scanning models and the actual value was 0.70 mm (0.51 mm on average). The measurement results of the same location were consistent among three scanning modes (0.00 mm). For the uniformity, the results of the normal mode were the best (3.62% on average), followed by the fast 1 mode (3.90% on average) and the fast 2 mode (4.84% on average). For the noise, the results of the normal mode were the best (15.69 on average), followed by the fast 2 mode (17.23 on average) and the fast 1 mode (21.74 on average). Regarding the high contrast resolution, the measurement results of three scanning modes were consistent (at least 3 pairs could be distinguished). For the low contrast resolution, the results of the fast 1 mode were the best (1.69 on average), followed by the normal mode (2.10 on average), and the fast 2 mode (2.31 on average). For the geometric accuracy, the measurement results of the three scanning modes were basically consistent with a mean deviation of 0.05 mm. The correlation of the measurement results between normal mode and fast 1 mode was the highest in clinical cases ( R2>0.90, P<0.01) with a high degree of consistency (95% consistency limit of the above two scanning modes< 1 mm threshold). Conclusion:Compared with the normal mode, the fast 1 mode can yield equivalent image quality, consistent registration results, faster scanning speed and lower scanning dose. Therefore, the fast 1 mode is recommended as the scan mode in clinical practice.

Objective:The Lorentz force produced by magnetic field deflects the paths of secondary electrons. The X-ray beam dosimetry characteristics of the magnetic resonance accelerator (MR-Linac) are different from conventional accelerators. The purpose of this study was to measure and analyze the X-ray beam dosimetry characteristics of 1.5T MR-Linac.Methods:In May 2019, our hospital installed a Unity 1.5T MR-Linac and measured it with magnetic field compatible tools. The measurement indexes include: surface dose, maximum dose point depth, beam quality, off-axis dose profile center, beam symmetry, penumbra width, output changes of different gantry angles.Results:The average surface dose was 40.48%, and the average maximum dose depth was 1.25 cm. The center of the 10 cm×10 cm beam field was offset by 1.47 mm to the x2 side and 0.3 mm to the y2 side. The x-axis symmetry was 101.33%, and the penumbra width on both sides was 6.86 mm and 7.14 mm, respectively. The y-axis symmetry was 100.85%, and the penumbra width on both sides was 5.92 mm and 5.95 mm, respectively. The maximum deviation of output dose with different gantry angles reached 1.50%. Conclusions:The surface dose of MR-Linac tend to be consistent, and the depth of the maximum dose point became shallower. The off-axis in the x-axis direction was shifted to the x2 side, which resulting in worse symmetry and penumbra asymmetry. The output dose at different angles has obvious variation and needs correction.

Chlorophyll content,leaf mass to per area,net photosynthetic rate and bioactive ingredients of Asarum heterotropoides var. mandshuricum,a skiophyte grown in four levels of solar irradiance were measured and analyzed in order to investigate the response of photosynthetic capability to light irradiance and other environmental factors. It suggested that the leaf mass to per area of plant was greatest value of four kinds of light irradiance and decreasing intensity of solar irradiance resulted in the decrease of leaf mass to per area at every phenological stage. At expanding leaf stage,the rate of Chla and Chlb was 3. 11 when A. heterotropoides var. mandshuricum grew in full light irradiance which is similar to the rate of heliophytes,however,the rate of Chla and Chlb was below to 3. 0 when they grew in shading environment. The content of Chla,Chlb and Chl( a+b) was the greatest value of four kinds of light irradiance and decreasing intensity of solar irradiance resulted in its decreasing remarkably( P<0. 05). The rate of Chla and Chlb decreased but the content of Chla,Chlb and Chl( a+b) increased gradually with continued shading. The maximum value of photosynthetically active radiation appeared at 10: 00-12: 00 am in a day. The maximum value of net photosynthetic rate appeared at 8: 30-9: 00 am and the minimum value appeared at 14: 00-14: 30 pm at each phenological stage if plants grew in full sunlight. However,when plants grew in shading,the maximum value of net photosynthetic rate appeared at about 10: 30 am and the minimum value appeared at 12: 20-12: 50 pm at each phenological stage. At expanding leaf stage and flowering stage,the average of net photosynthetic rate of leaves in full sunlight was remarkably higher than those in shading and it decreased greatly with decreasing of irradiance gradually( P < 0. 05). However,at fruiting stage,the average of net photosynthetic rate of leaves in full sunlight was lower than those in 50% and 28% full sunlight but higher than those in 12% full sunlight. All photosynthetic diurnal variation parameters of plants measured in four kinds of different irradiance at three stages were used in correlation analysis. The results suggested that no significant correlation was observed between net photosynthetic rate and photosynthetically active radiation,and significant negative correlation was observed between net photosynthetic rate and environmental temperature as well as vapor pressure deficit expect for 12% full sunlight. Positive correlation was observed between net photosynthestic rate and relative humidity expect for 12% full sunlight. Significant positive correlation was observed between net photosynthetic rate and stomatal conductance in the four light treatments. Only,in 12% full sunlight,the net photosynthetic rate was significantly related to photosynthetically active radiation rather than related to environmental temperature,vapor pressure deficit and relative humidity. In each light treatment,a significant positive correlation was observed between environmental temperature and vapor pressure deficit,relative humidity as well as stomatal conductance. Volatile oil content was 1. 46%,2. 16%,1. 56%,1. 30% respectively. ethanol extracts was 23. 44%,22. 45%,22. 18%,21. 12% respectively. Asarinin content was 0. 281%,0. 291%,0. 279% and 0. 252% respectively. The characteristic components of Asarum volatile oil of plant in different light treatments did not change significantly among different groups.
Asarum ; physiology ; radiation effects ; Chlorophyll ; analysis ; Photosynthesis ; Plant Leaves ; radiation effects ; Sunlight