Objective:To explore the predictive effect of European treatment and outcome study long term survival (ELTS) score on survival outcomes in chronic myeloid leukemia of chronic phase (CML-CP) children.Methods:A single-center retrospective cohort study was conducted. Clinical data of 216 children with CML-CP in Peking University People′s Hospital from January 2010 to December 2023 were analyzed. Children were divided into low, intermediate and high-risk groups according to ELTS score. The survival outcomes and prognostic factors were analyzed. Kaplan-Meier method and Log-Rank test were used for survival analysis.Cox regression model was applied for analysis of prognostic factors.Results:Among the 216 children with CML-CP, there were 122 males and 94 females, with the diagnosis age of 11.0 (8.0, 14.7) years. The follow-up time was 77 (57, 99) months. According to ELTS score, 145, 52, and 19 children were classified as low, intermediate and high-risk group. For the low-risk and intermediate/high-risk groups, the 6-year failure-free survival (FFS) rates were (83.0±3.1)% and (64.6±5.7)%, the 6-year progression-free survival (PFS) rates were (91.4±2.3)% and (78.7±4.8)%, and the 6-year event-free survival (EFS) rates were (80.8±3.3)% and (64.2±5.7)%, with statistically significant difference ( χ2=9.45, 7.16, 7.40, P=0.002, 0.007, 0.007), respectively.The 6-year overall survival (OS) rates were (98.5±1.0)% and (95.6±2.4)%, without statistically significant difference ( χ2=0.35, P=0.550). Multivariate analysis showed that ELTS score was an independent prognostic factor or tendency for FFS ( HR=1.97, 95% CI 1.11-3.49), PFS ( HR=2.95, 95% CI 1.18-7.39), and no independent prognostic factor for EFS and OS were found. Conclusions:ELTS score at diagnosis can help stratify the risk of children with CML-CP. The children in intermediate/high-risk group are more likely to have treatment failure, disease progression than those in low-risk group, but the predictive ability of ELTS score for OS is limited.

Objective:To explore the clinical characteristics and prognosis of children with chronic myeloid leukemia in the blast phase (CML-BP) .Methods:The clinical characteristics, treatment measures, and survival outcomes of 28 children with CML-BP were analyzed in our hospital from January 2008 to November 2022.Results:The male to female ratio of the 28 children with CML-BP was 1.15∶1. The median age of diagnosis of CML-BP was 10 years, and the median follow-up time was 79 months. During the diagnosis of CML, four children were in the BP, one was in the accelerated phase (AP) and 23 children were in the chronic phase (CP). Among the 23 children with CML-CP, 75% had progressed directly from CP to BP without experiencing the AP. Among the children diagnosed with CML-BP, 71.4% were classified as chronic myeloid leukemia lymphoid blast phase (CML-LBP), 25.0% belonged to the chronic myeloid leukemia myeloid blast phase (CML-MBP), and 3.6% belonged to the chronic myeloid leukemia mixed phenotype acute leukemia (CML-MPAL). Treatment with hemaopoietic stem cell transplantation (HSCT) after tyosine kinase inhibitor (TKI) combined with chemotherapy was administered to 19 children, two children received HSCT after TKI alone, and seven children received TKI combined with chemotherapy but without HSCT. The 5-year overall survival of the 28 children with CML-BP was 59.3%.Conclusion:The direct progression of BP from CP is greater in children with CML-BP compared with adults, and the overall prognosis of children with CML-BP is poor.

Objective:To evaluate the role of the AMP-activated protein kinase (AMPK)-silent information regulator 1 (SIRT1)-nuclear factor-κB (NF-κB) signaling pathway in reduction of brain injury by panax notoginseng saponins (PNS) in mechanically ventilated rats.Methods:Seventy-two SPF-grade male Sprague-Dawley rats, aged 10 weeks, weighing 357-377 g, were divided into 6 groups ( n=12 each) by a random number table method: sham operation group, model group, PNS low dose group, PNS medium dose group, PNS high dose group, and PNS high dose+ compound C group. PNS 12.5, 25 and 50 mg/kg were intraperitoneally injected in PNS low dose group, PNS medium dose group and PNS high dose group, respectively. In PNS high dose+ compound C group, PNS 50 mg/kg was intraperitoneally injected, and 10 min later compound C 0.2 mg/kg was injected via the tail vein. Normal saline 10 ml/kg was intraperitoneally injected in sham operation group and model group. Drugs or normal saline was injected at 30 min before mechanical ventilation in each group. Mechanical ventilation model: The animals were mechanically ventilated for 6 h, with ventilation frequency 40 times/min, tidal volume 40 ml/kg in model group; The animals were mechanically ventilated for 6 h, with tidal volume 10 ml/kg in sham operation group. Morris water maze test was used to detect the learning and memory function of rats, the concentrations of serum interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) and dopamine (DA) were detected by enzyme-linked immunosorbent assay, the neuronal counts in the hippocampal CA1 region were determined by Nissl staining, and the expression of P2Y1 purine receptor (P2Y1R), dysbindin-1 and AMPK in hippocampal CA1 region was detected by Western blot. The phosphorylated SIRT1 (p-SIRT1) to SIRT1 ratio and phosphorylated NF-κB p65 (p-NF-κB p65) to NF-κB ratio in hippocampal CA1 region was calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the time of staying at the target platform quadrant was shortened, the serum concentrations of IL-1β, IL-6 and TNF-α were increased, the serum DA concentration was decreased, the nerve count in hippocampal CA1 region was decreased, the expression of P2Y1R and dysbindin-1 was up-regulated, the expression of AMPK was down-regulated, the p-SIRT1/SIRT1 ratio was decreased, and the p-NF-κB p65/NF-κB p65 ratio was increased in model group ( P<0.05). Compared with model group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the time of staying at the target platform quadrant was prolonged, the serum concentrations of IL-1β, IL-6 and TNF-α were decreased, the serum DA concentration was increased, the nerve count in hippocampal CA1 region was increased, the expression of P2Y1R and dysbindin-1 was down-regulated, the expression of AMPK was up-regulated, the p-SIRT1/SIRT1 ratio was increased, and the p-NF-κB p65/NF-κB p65 ratio was decreased in PNS low dose group, PNS medium dose group and PNS high dose group ( P<0.05). Compared with PNS high dose group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the time of staying at the target platform quadrant was shortened, the serum concentrations of IL-1β, IL-6 and TNF-α were increased, the serum DA concentration was decreased, the nerve count in hippocampal CA1 region was decreased, the expression of P2Y1R and dysbindin-1 was up-regulated, the expression of AMPK was down-regulated, the p-SIRT1/SIRT1 ratio was decreased, and the p-NF-κB p65/NF-κB p65 ratio was increased in PNS high dose+ compound C group ( P<0.05). Conclusions:The mechanism by which PNS reduces brain injury may be related to activation of the AMPK-SIRT1-NF-κB signaling pathway in mechanically ventilated rats.

Objective:To evaluate the impacts of tissue heterogeneity on dose calculation of cervical brachytherapy by comparing the doses calculated by two clinically used dose calculation method and the CT image-based Monte Carlo (MC) method.Methods:This study retrospectively selected 11 patients with cervical cancer treated with 3D brachytherapy in Anhui Provincial Cancer Hospital from January 2018 to June 2020. The dose distribution of each plan was calculated via three methods, dose calculation method described in American Association of Physicist in Medicine(AAPM) Task Group No. 43 Report (TG43-BT), Acuros BV(BV-BT) used to perform accurate dose calculations in high-dose-rate (HDR) brachytherapy with phantom heterogeneity, and CT image-based EGSnrc tool kit used to perform Monte Carlosimulation (MC-BT). The dose volumes( V3 Gy, V6 Gy, V9 Gy, and V12 Gy), target volume doses( D98, D90, D50), D2 cm 3 of organs at risk (OARs) calculated by the three methods were compared. Results:The HRCTV D90obtained by TG43-BT was 6.274 Gy, which was even overestimated by around 5% compared to the result calculated by MC-BT. Meanwhile, TG43-BT overestimated the dose volumesand the target volume doses compared to MC-BT.Except for D50 and V12 Gy, the differences between the doses to tumor calculated by BV-BT and MC-BT were not statistically significant( P>0.05). There was also no significant statistical difference between the D2 cm 3 of rectum, small intestine, and sigmoid calculated by BV-BT and MC-BT ( P>0.05). In contrast, the dose to D2 cm 3 of bladder determined by MC-BT was 4.609 Gy, which was notably higher than those deter mined by TG43-BT and BV-BT. Conclusions:TG43-BT overestimated the doses to tumor targets and most OARs since the effects of tissue heterogeneity were not taken into consideration. BV-BT performed efficient calculation and most of the dose distributionin target volume and OARs obtained by BV-BT were consistent with that calculated by MC-BT. Nevertheless, low accuracy occurred for the regions near the sources and full bladder, which warrants further caution in clinical evaluation.

Objective:To investigate the impacts of the composition and physical density of tissue on the dose distribution of implanted 125I seeds, in order to provide references for the clinical dose calculation and assessment of implanted radioactive particles. Methods:The OncoSeed 6711 physical model of 125I seeds was established using thes of twareegs_brachy and was validated through the calculation of dose rate constant and the radial dose function [ g( r)] in water. Then, based on the element composition and physical density of different types of tissue, the g( r) and absorbed dose ratein water, prostate, breast, muscle, and bone were calculated. Results:The calculated dose rate constant (0.950 cGy·h -1·U -1) and g( r)in water approached the values in related literature. The absorbed dose in bone was 6.042 times than that in water at a distance of 0.05 cm from the implanted source. The difference between the absorbed doses in breast and water was more than 10% at a distance of less than 1.7 cm from the implanted source. The difference between the absorbed doses in prostate/muscle and water was less than 5% at the same radial location. Conclusions:The dose distribution of 125I seeds in some types of human tissue is significantly different from that in water, which should be carefully considered in clinical dose calculation.

Objective:To develop a deep learning model for predicting three-dimensional (3D) voxel-wise dose distributions for intensity-modulated radiotherapy (IMRT).Methods:A total of 110 postoperative rectal cancer cases treated by IMRT were considered in the study, of which 90 cases were randomly selected as the training-validating set and the remaining as the testing set. A 3D deep learning model named 3D U-Res-Net was constructed to predict 3D dose distributions. Three types of 3D matrices from CT images, structure sets and beam configurations were fed into the independent input channel, respectively, and the 3D matrix of IMRT dose distributions was taken as the output to train the 3D model. The obtained 3D model was used to predict new 3D dose distributions. The predicted accuracy was evaluated in two aspects: the average dose prediction bias and mean absolute errors (MAEs)of all voxels within the body, the dice similarity coefficients (DSCs), Hausdorff distance(HD 95) and mean surface distance (MSD) of different isodose surfaces were used to address the spatial correspondence between predicted and clinical delivered 3D dose distributions; the dosimetric index (DI) including homogeneity index, conformity index, V50, V45 for PTV and OARs between predicted and clinical truth were statistically analyzed with the paired-samples t test. Results:For the 20 testing cases, the average prediction bias ranged from -2.12% to 2.88%, and the MAEs varied from 2.55% to 5.75%. The DSCs value was above 0.9 for all isodose surfaces, the average MSD ranged from 0.21 cm to 0.45 cm, and the average HD 95 varied from 0.61 cm to 1.54 cm. There was no statistically significant difference for all DIs, except for bladder Dmean. Conclusions:This study developed a deep learning model based on 3D U-Res-Net by considering beam configurations input and achieved an accurate 3D voxel-wise dose prediction for rectal cancer treated by IMRT.

Objective To evaluate the feasibility of utilizing dose-volume histogram (DVH) prediction models of organs at risk (OARs) to deliver automatic treatment planning of prostate cancer.Methods The training set included 30 cases randomly selected from a database of 42 cases of prostate cancer receiving treatment planning.The bladder and rectum were divided into sub-volumes (Ai) of 3 mm in layer thickness according to the spatial distance from the boundary of planning target volume (PTV).A skewed normal Gaussian function was adopted to fit the differential DVH of Ai,and a precise mathematical model was built after optimization.Using the embedded C++ subroutine of Pinnacle scripa,ahe volume of each Ai of the remaining validation set for 12 patients was obtained to predict the DVH parameters of these OARa,ahich were used as the objective functions to create personalized Pinnacle script.Finalla,automatic plans were generated using the script.The dosimetric differences among the original clinical plannina,aredicted value and the automatic treatment planning were statistically compared with paired t-test.Results DVH residual analysis demonstrated that predictive volume fraction of the bladder and rectum above 6 000 cGy were lower than those of the original clinical planning.The automatic treatment planning significantly reduced the V70,V60,V50 of the bladder and the V70 and V60 of the rectum than the original clinical planning (all P＜0.05),the coverage and conformal index (CI) of PTV remained unchangea,and the homogeneity index (HI) was slightly decreased with no statistical significance (P＞ 0.05).Conclusion The automatic treatment planning of the prostate cancer based on the DVH prediction models can reduce the irradiation dose of OARs and improve the treatment planning efficiency.

Objective To study the dosimetric parameters of Varian GammaMed Plus HDR 192 Ir source via Monte Carlo ( MC ) method based on the recommendation of the American Association of Physicist in Medicine ( AAPM) and European Society for Radiotherapy and Oncology ( ESTRO) . Methods Using the Monte Carlo program EGSnrc, an accurate model of 192 Ir source for MC calculations was establish firstly. Through formula derivation, bilinear interpolation and unit conversion, the air kerma strength per unit source activity, the dose rate constant, radial dose function and anisotropy function was obtained then , and compare the result with those in other published studies. Results The air kerma strength per unit source activity was 9. 781 × 10-8 U/Bq. The dose rate constant was 1. 113 cGy · h-1 · U-1 , with a discrepancy of less than 0. 4％ compared with result published in other works. Furthermore, the curves of radial dose function and anisotropy function overall agree with the data shown in the literature. Conclusions The feasibility of performing dosimetric studies of 192 Ir source using the MC software EGSnrc was demonstrated. This work provides a theoretical guidance on analysis of the dose distribution of brachytherapy and on evaluation of the dose accuracy of clinical radiotherapy.

Clustered regularly interspaced short palindromic repeats (CRISPR) is an acquired immune system existing in archaea and bacteria with the long-term process of evolutionary.CRISPR/Cas9 gene editing system is a new type of gene editing technology developed based on the system.CRISPR/Cas9 is a more efficient method for gene targeting than the previous methods.It has been successfully applied for gene-modified of eukaryotes since 2012,but the reports about pathogenic microorgaisms are rarely.Here,the research progress in the structure,mechanism of CRISPR/Cas9 system and its applications on pathogenic microorgaisms is reviewed.

Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. vaccae Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. vaccae BCG revealed that M. vaccae was more malignant than M. vaccae in mice. We also demonstrated that serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺ cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.
Animals ; Bacillus ; Bacteria ; Chemokine CCL2 ; Flow Cytometry ; Injections, Intraperitoneal ; Interferon-gamma ; Interleukin-10 ; Interleukin-12 ; Interleukins ; Lymph Nodes ; Mice* ; Mycobacterium bovis ; Mycobacterium* ; Pathology ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha