The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. Radix Astragali, used as both medicine and food, exerts the effects of tonifying spleen and qi. Astragalus polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of Radix Astragali, which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1β (IL-1β), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-‍κB (TLR4/NF-‍κB) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella, and increasing that of Parasutterella, Parabacteroides, Clostridium XIVb, Oscillibacter, Butyricicoccus, and Dorea. APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.
Rats ; Animals ; NF-kappa B/metabolism* ; Spleen ; Gastrointestinal Microbiome ; Toll-Like Receptor 4 ; Polysaccharides/pharmacology* ; Astragalus Plant/metabolism* ; Immune System Diseases/drug therapy* ; Body Weight

Objective:To compare the leaf open time (LOT) parameters and γ passing rates between the 4.0.4 and 4.2.3 helix Tomotherapy planning systems and evaluate the improvement.Methods:Retrospective comparison of the treatment plans of 345 cases selected by 4.0.4 and 4.2.3 versions was performed. The Machine Specific Sinogram of each plan was extracted from the archived plan file to calculate the LOT. The evaluated LOT parameters included the projection time, the maximum LOT, the mean non-zeros time, the time difference between the projection time and the maximum LOT, the relative count of leaves with LOT greater than maximum LOT minus 5 ms, the relative count of leaves with LOT lower than 100 ms and the beam on time. The γ passing rate (criteria: 3 mm/3%, 10% threshold and global error) and the LOT parameters between two version systems were evaluated with the independent t-test. The relationship between the LOT parameters and γ passing rate was analyzed by the multiple linear regression method. Results:The γ passing rate of the Ver 4.0.4 system was 97.86%, significantly lower than 98.6% of the Ver 4.2.3 system ( P<0.001). The time gap between the projection time and the maximum LOT of the Ver 4.2.3 system was significantly less than that of the Ver 4.0.4 system (1 ms vs. 11 ms, P<0.001). For the Ver 4.0.4 system, the multiple linear regression method showed that the maximum LOT ratio and the beam on time were negatively correlated with the γ passing rate (both P<0.001). However, for the Ver 4.2.3 system, only the beam on time showed a negative correlation with the γ passing rate ( P<0.001). Conclusion:The γ passing rate of the Ver 4.2.3 system is significantly higher than that of the Ver 4.0.4 system. The decrease of γ passing rate caused by the leaves near the maximum LOT is properly resolved in the new version system.

Objective:To evaluate the sensitivity of the ArcCheck dosimetry system in detecting the leaf open time errors during the center and off-center helical tomotheray delivery quality assurance (DQA).Methods:Nine nasopharyngeal carcinoma (NPC) patients were selected in this study. Two DQA plans were created for each patient: the" center" plan was created by moving the image of the ArcCheck phantom to place the high dose region on the phantom center and the " off-center" plan was created by offsetting the phantom and putting several diodes through a higher does region. Leaf open time errors of 2, 4, 6, 8 and 10 ms were introduced to the Sinogram which was modified using Matlab. Each intentional error plan and original (no error) plan for each patient were measured using both " center" and " off-center" DQA methods, the γ analysis was performed to evaluate the DQA results. The different dose and distance error criteria of 3%/3 mm, 3%/2 mm and 2%/2 mm were selected, and different thresholds of 5%, 10% and 15% were selected for γ analysis. The gradient and the minimum detectable error approach were taken to quantitatively analyze the sensitivity. The correlation between different dose distance error criteria and different thresholds was also evaluated by Pearson correlation analysis. Results:The absolute value of γ gradient of the " center" DQA plans were larger than those of the " off-center" plans in all different γ criteria (all P<0.05). The stricter the γ criteria were adopted, the more sensitive DQA results of leaf open time error were obtained. The minimum detectable error was 2 ms in all different γ criteria for the " center" DQA plan. The minimum error detectability of the " off-center" DQA plan was weaker than that of the " center" DQA plan. The γ passing rates of three different dose distance error criteria were significantly strongly correlated for the " center" DQA plan ( R2>0.9). For the " off-center " DQA plan, only the 3%/3 mm and 3%/2 mm criteria were significantly strongly correlated ( R2>0.9). Significant strong correlation was observed in the γ passing rate at different thresholds between the " off-center" and " center" DQA plans. Conclusions:The " center" DQA plan method is more sensitive than the " off-center" DQA plan method in all γ criteria, and the γ passing rates in different γ criteria are strongly correlated for the " center" DQA plan. The " center" DQA plan method is recommended.

Objective: To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test. Methods: One hundred and seventy-five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing. Results: The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients. Conclusions The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.

Objective To evaluate the dosimetric characteristics of the TomoDose diode and its application in detecting the couch velocity and assessing the beam Profile stability for convenient and efficient quality control of Tomotherapy.Methods Fundamental properties of the TomoDose detector,such as dose linearity,dose per pulse dependence,directional dependence and field size dependence were tested by the water-equivalent phantom and the results were statistically compared with those measured by the ion-chamber (0.057 cm3,A 1SL).Five different couch velocities with a time interval of 0.0005 s were designed to test the sensitivity of TomoDose for detecting the couch velocity,and then the clinical data of 7 patients with different couch velocities were selected to verify the test accuracy.The beam profile of three different jaws of 1.0,2.5 and 5.0 cm were measured using TomoDose with water-equivalent phantom in the x and y directions under the same conditions as water tank with an underwater depth of 15,50,100,150 and 200 mm,respectively.The Profile data obtained by water tank and TomoDose were evaluated using the Gamma (γ) evaluation method with the 2％/1 mm criterion.Results The dose linearity of the TomoDose and ion chamber was in a linear pattern within the beam-on-time ≤ 30 s.The difference between the TomoDose and ion chamber was less than 2％ for the dose per pulse dependence,and the response trends of them were consistent.TomoDose showed angular response dependence with a maximum difference of 2.53％ for the gantry angle of ±60°.For the field size dependence,the response difference between the TomoDose and ion chamber was increased with the decreasing field size when the Jaw was 5.0 cm,and the maximum deviation was 0.78％ when the field size was 5.0 cm×2.5 cm.TomoDose could detect the couch distance error of 0.5 mm,and determine the couch velocity deviation of＜ 0.6％.For the Profile stability testing:In the x direction,there was always γ＜1 at the underwater depth of 15 mm for all values of Jaw;when the underwater depth was not 15 mm,there was always γ＜ 1 in the main beam region (off-axis distance＜ 200 mm),whereas in the penumbra region (off-axis distance＞ 200 mm),the value of γ was larger and even with γ＞ l.In the y direction,all comparison results of Profile under three field width demonstrated that γ index was larger on the edge of beam,whereas γ＜1 was found in all cases.Conclusions TomoDose is suitable f or the quality control of Tomotherapy,which can accurately measure the couch velocity,precisely monitor the stability of beam Profile of Tomotherapy and complete the quality control process in a convenient and efficient manner.

Objective To analyze the concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations detected in plasma and matched tumor tissues in colorectal cancer patients, in order to provide good evidences to support plasma could be a potential surrogate of tumor tissue for gene mutation test. Methods One hundred and seventy?five cases of colorectal cancer were collected at the First Hospital of Jilin University, from October 2016 to October 2017.There were 101 males and 74 females, their ages ranged from 28 to 85 years,with median age of 59 years. The KRAS, NRAS, BRAF and PIK3CA gene mutations in the plasma and paired tumor specimens of all patients were detected by next generation sequencing. Results The results of tissue samples test were gold standard. Comparison of the four genes showed that concordance rates between plasma and tissue samples were 81.1%(Kappa=0.543), 99.4%(Kappa=0.886), 99.4% (Kappa=0.886) and 97.7%(Kappa=0.714) respectively for KRAS, NRAS, BRAF and PIK3CA. The plasma detection rates of these genes were related to tumor stage(P=0.001), but not to gender(P=0.468) and age(P=1.000) of patients. Conclusions The study shows a high concordance of KRAS, NRAS, BRAF and PIK3CA gene mutations in plasma against mutation status in tumor tissue. In colorectal cancer, tumor tissue remains the best specimen for gene detection. However, patients from tumor tissue specimens cannot be obtained, especially those with advanced metastases, plasma can be used instead of tissue to detect the mutation status of KRAS, NRAS, BRAF and PIK3CA to guide targeted therapy.

Objective To investigate the impact of injection current (IC), injection voltage (IV), and pulse forming network (PFN) on energy (depth ratio D20/D10) and profiles of helical tomotherapy, and to improve the quality control for the stability of beam characteristics.Methods The energy and profiles were measured by ion chamber and TomoDose at different values of IC, IV, and PFN, the relationship between the energy and various parameters was evaluated by Pearson correlation analysis, and the changes in profiles were evaluated by comparative analysis.Results The energy had no correlation with IV and PFN values (P>0.05), but had a strong correlation with IC value (P=0.007), which showed a downward trend with the increase in IC.For the profiles in the x direction:(1) in the main beam region (-200 to 200 mm), the shoulder area of the profiles increased regularly with the increase in IC.There were no significant changes for the profiles when the IV values ranged from 6.42 V to 6.54 V, and the shoulder area of the profiles reached the highest point with IV=6.60 V, then decreased with further increase in IV.The shoulder area of the profiles decreased regularly with the increase in PFN.(2) In the penumbral region (±200 mm outside), all the three parameters had no effect on the profiles.For the profiles in the y direction:(1) in the main beam region (-20 to 20 mm), the profiles showed an upward trend in the area with an off-axis distance less than 16 mm when IC values were 5.40 V and 5.46 V, and showed an upward trend in the area with an off-axis distance less than 16 mm.But on the whole, the shoulder area of the profiles increased with the increase in IC, and was not affected by IV and PFN.(2) In the penumbral region (±20 mm outside), the profiles decreased regularly with the increase in IV, and was not affected by IC and PFN.IC had the highest influence on the profiles in the main beam region, followed by PFN and IV.Only IV had impact on the profiles in the penumbral region.Conclusions When the energy needs to be adjusted, the IC value should be given a priority, and PFN should be taken as a supplementary factor.When the profile needs to be adjusted, the IC value should be given a priority, and IV should be used as an auxiliary factor in the main beam region.But in the penumbral region, adjustment of parameters is only related to the profiles in y direction, so the IV value should be adjusted.This study has a guiding role in the quality control of energy and profiles, which can reduce the blindness of quality control, thus saving the time.

Objective To compare two different methods to detect the differences of gene mutation rate, sensitivity, specificity and coincidence rate of epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) so as to assess the clinical value of qRT-PCR method and its environmental-friendly technologyplatforms.One uses environmental fixative poly hydroxyl acrylic acid and green transparent liquid dewaxing Van-clear alone or in combination to replace the traditional fixative 4％ (volume fraction) neutral buffered formalin and the traditional transparent dewaxing liquid xylene in application of quantitative real-time polymerase chain reaction (qRT-PCR).The other uses traditional reagents in direct sequencing.Methods We selected 91 cases of primary NSCLC specimens resected between May 2013 and March 2016 in Zhongshan Bo`ai Hospital and Zhongshan Hospital of Traditional Chinese Medicine.Five samples were taken from the same tumor lesion.We used a random number table to randomly divide these samples into Groups A, B , C, D, and E.Group A received direct sequencing method in detection of EGFR gene mutations.Besides, during the experiment, 4％ neutral buffered formalin was used for fixing, and xylene transparent dewaxing was used to make slices for DNA extraction dewaxing.Group B received qRT-PCR method to detect EGFR gene mutations.Meanwhile, during the experiment, 4％ neutral buffered formalin was used for fixing, and xylene transparent dewaxing was used to make slices for DNA extraction dewaxing.Group C received qRT-PCR method in detection of EGFR gene mutations.At the same time, during the experiment, polyhydroxy acrylic acid was used for fixing, and xylene transparent dewaxing was used to make slices for DNA extraction dewaxing.Group D received qRT-PCR method to detect EGFR gene mutations.In the meantime, 4％ neutral buffered formalin was used for fixing, Van-clear transparent dewaxing was used to make slices for DNA extraction dewaxing.Group E received qRT-PCR method in detection of EGFR gene mutations.In addition, during the experiment, polyhydroxy acrylic acid was used for fixing, and Van-clear transparent dewaxing was used to make slices for DNA extraction dewaxing.In addition, during the experiment, polyhydroxy acrylic acid was used for fixing, and Van-clear transparent dewaxing was used to make slices for DNA extraction dewaxing.The mutations of Exons 18, 19, 20, and 21 in EGFR genes were respectively determined in the five groups of NSCLC.Results ① Groups B, C, D, E and A did not significantly differ in the percentage of people with mutations or target site mutation rates of EGFR genes in NSCLC (P> 0.05).② The detection results of EGFR target site mutation in Groups B, C, D, E and A had good sensitivity, strong specificity, and high compliance rate.Conclusion The green transparent liquid dewaxing Van-clear alone or in combination to replace the traditional fixative 4％ neutral buffered formalin and the traditional transparent dewaxing liquid xylene in the application of qRT-PCR so as to detect EGFR gene mutations in NSCLC has good consistent results compared with the method that uses traditional reagents in direct sequencing.It has the significance and value in clinical application.

Objective To quantitatively investigate the image quality and dose calculation accuracy of megavoltage computed tomography (CT) in helical tomotherapy.Methods The megavoltage CT was used to scan the Cheese phantom,and the geometric accuracy of images,noise,image uniformity,spatial resolution,density-CT value conversion,and dose calculation accuracy were analyzed and compared with conventional kilovoltage CT.Results The geometric accuracy of megavoltage CT images was within 2 mm in three directions.The megavoltage CT was inferior to kilovoltage CT in terms of image noise,uniformity,and spatial resolution.The dose-volume histogram (DVH) in dose reconstruction based on CT images was well consistent with DVH in the kilovohage CT plan.Conclusions The megavoltage CT can obtain images with accurate geometric dimensions and has a low imaging dose and accurate dose calculation,which meets clinical requirements.