Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F

Purpose To design PCR combined probes u-sing TaqMan technology to detect the expression of major driver genes in a variety of soft tissue sarcomas at one time,and to dis-cuss whether the combined probes can better assist clinicopatho-logical diagnosis based on histological features and FISH results.Methods Our research group designed 32 pairs of fusion gene probes related to soft tissue sarcoma based on TaqMan tech-nique,involving 10 types of sarcoma.The histopathological specimens of 70 patients with common fusion gene soft tissue sarcoma in our hospital were examined by fusion gene combina-tion,and the histopathological specimens of 30 patients with oth-er soft tissue sarcoma without fusion gene were set as controls.Individual common sarcoma types were analyzed with FISH probe detection.At the same time,the detection performance of the combined probe was evaluated by various methods.Results The soft tissue sarcoma-related fusion gene probe designed by our research group was used to detect the confirmed soft tissue sarcomas,and the results showed that the highest sensitivity was 100％.Among the three types of tumors,protuberant dermatofi-brosarcoma,synovial sarcoma and mucinous liposarcoma were verified by FISH,and the coincidence rate of the two methods was high,with no statistical significance(P＞0.05).The re-sults of interlot and intralot reproducibility of protuberous derma-tofibrosarcoma,mucinous liposarcoma and synovial sarcoma were consistent.Three different concentration limits were used to de-tect the positive plasmid of all the fused gene RNA,and 25 cop-ies/μL was the lowest concentration limit.Conclusion Com-bined with the pathological diagnosis results,TaqMan technology can be used to design PCR combined probes for soft tissue sarco-ma,which have high sensitivity and high specificity and good methodological performance,and meet the needs of primary medical institutions for one-time and rapid auxiliary pathological diagnosis of common soft tissue sarcoma.It provides a rapid and reliable method for the detection of multiple fusion genes in clin-ical soft tissue sarcoma.

Background Few studies have investigated the association between air pollution and arterial stiffness in Chinese population, and the findings are inconsistent. The problem of multicollinearity exists when modeling multiple air pollutants simultaneously. Objective To investigate potential association between air quality index (AQI) and population brachial-ankle pulse wave velocity (baPWV) in Beijing. Methods This study retrieved medical examination data of 2971 participants from the Beijing Health Management Cohort, who were under 60 years old and not yet retired, from January 1, 2015 to December 31, 2019. The most recent medical examination data available were utilized for this analysis. AQI data from 35 air pollution monitoring sites in Beijing and meteorological data (including atmospheric pressure, air temperature, wind speed, and relative humidity) from 16 meteorological monitoring stations from January 1, 2014 to December 31, 2019 were collected. An average AQI exposure level for 365 d before the date of physical examination for each participant was computed using inverse distance weighting. Multiple linear regression analysis was employed to investigate the relationship between AQI and baPWV in Beijing, after adjusting for confounding variables including age, gender, body mass index, mean arterial pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting blood glucose, atmospheric pressure, temperature, wind speed, relative humidity, medication history of diabetes, medication history of hypertension, cardiovascular disease, education, smoking status, drinking status, and physical activity intensity. Subgroup analysis was performed by age, sex, presence of diabetes, and presence of hypertension. Results AQI demonstrated an overall decreasing trend during the study period and was lower in the northern regions and higher in the southern regions of Beijing. After adjusting the confounding variables, each 10 unit increase in AQI was associated with 6.18 (95%CI: 1.25, 11.10) cm·s⁻¹ increase in baPWV in all participants, 8.05 (95%CI: 2.32, 13.79) cm·s⁻¹ increase in the participants <50 years, 15.82 (95%CI: 8.33, 23.31) cm·s⁻¹ increase in the female group, 10.10 (95%CI: 4.66, 15.55) cm·s⁻¹ increase in the participants without diabetes, and 9.41 (95%CI: 4.21, 14.62) cm·s⁻¹ increase in the participants without hypertension. However, there was no statistically significant association observed between AQI and baPWV in the age group ≥50 years, the male group, the diabetic group, and the hypertensive group (P>0.05). Conclusion An increase in long-term AQI levels is associated with an elevation in the degree of arterial stiffness. Individuals under 50 years old, females, without hypertension or diabetes are susceptible populations to arterial stiffness when being exposed to air pollution. Improving air quality may contribute to prevent arterial stiffness.

Objective:To propose an automatic planning approach for Eclipse15.6 planning system based on Eclipse scripting application programming interface (ESAPI) and evaluate its clinical application.Methods:20 patients with nasopharyngeal carcinoma and 20 cases of rectal cancer were selected in the clinical planning. The developed automatic planning script SmartPlan and RapidPlan were used for automatic planning and dosimetric parameters were compared with manual planning. The differences were compared between two groups by using Wilcoxon signed rank test. Results:The dosimetric results of automatic and manual plans could meet clinical requirements. There was no significant difference in target coverage in nasopharyngeal carcinoma planning between two groups ( P>0.05), and automatic plans were superior to manual plans in organs at risk sparing ( P<0.05). Except for the homogeneity index of PTV and the maximum dose of bowel in rectal cancer plans, the other dosimetric parameters of the automatic plans were better than those of the manual plans (all P<0.05). Conclusions:Compared with the manual plans, the automatic plans have the same or similar target coverage, similar or better protection of organs at risk, and more convenient implementation. The developed SmartPlan based on ESAPI has clinical feasibility and effectiveness.

Objective:To investigate the clinicopathological features of fumarate hydratase (FH) deficiency uterine leiomyoma.Methods:The data of 38 patients with FH deficiency uterine leiomyoma were screened and analyzed. The expressions of FH, S-(2-succino)-cysteine (2SC), desmin, p16, p53, CD 10 and cell proliferation associated nuclear antigen (Ki-67) proteins were detected by immunohistochemistry, and their clinicopathological features were analyzed retrospectively. Results:(1) Clinical features: the median age of the patients was (42.5±7.4) years old. Twenty-one cases (55%) of them were myomas found in physical examination, and the median maximum diameter of the tumor was 6.0 cm (range: 5.0-7.5 cm); myomectomy was performed in 23 cases (61%), total hysterectomy with or without bilateral appendages in 15 cases (39%); laparoscopic surgery in 27 cases (71%), open surgery in 11 cases (29%); none of the patients had renal cell carcinoma. (2) Histological features: atypical nuclear cells were distributed locally or diffusely, eosinophilic nucleoli and intranuclear inclusion bodies could be seen, glass like globules could be seen in the cytoplasm, nuclear division was 0-4/10 high power field (HPF), and antler like blood vessels and pulmonary edema-like changes could be seen in the stroma. Among 38 patients with FH deficiency uterine leiomyoma, FH was negative in 37 cases (97%), and positive in 1 case (3%); 2SC, desmin, p16, p53, CD 10 and Ki-67 showed focal positive expression in 38 cases (100%), including 35 cases (92%) with Ki-67 index<10% and 3 cases (8%) with Ki-67 index ≥10%. (3) Follow-up: 4 cases (11%) recurred, and there was no death. There were significant differences in age, family history, distribution of atypical nuclei and mitosis number between recurrent group and non-recurrent group (all P<0.05). Conclusions:FH deficiency uterine leiomyoma is a rare tumor, which needs pathological examination,immunohistochemical examination and clinical history. Patients younger than 43 years old, with family history, histologically atypical diffuse nuclear distribution and mitotic number ≥3/10 HPF should be alert to the risk of recurrence.

Objective:To evaluate the effect of radical image-guided radiotherapy (IGRT) on the target dose in cervical cancer and investigate the appropriate application mode.Methods:Twenty patients with cervical cancer treated with helical tomotherapy (HT) in Seventh Medical Center of PLA General Hospital from 2012 to 2016 were selected. A megavoltage CT (MVCT) scan was performed before each treatment. The obtained MVCT images were used for dose parameter in the adaptive module of HT to obtain the actual dose (Plan 1) and the non-image-guided dose parameter was simulated (Plan 2). Each single dose distribution and the corresponding fused CT images were transferred to the software Mimvista 6.5 to obtain the total radiation dose parameter by dose superposition.Results:The motion of CTV, uterus and GTV in Plan 2 was significantly larger than that of Plan 1(all P<0.05), and the largest changes were seen in the ventrodorsal and uterine direction. The V 45Gy, V 50Gy, D 98% and D mean of CTV and uterus and V 50Gy of GTV in Plan 2 were significantly decreased compared with those in Plan 1(all P<0.05). The left-right motion of Plan 1 was negatively correlated with D 2% and D 98% of CTV and uterus (both P<0.05). The head-foot motion was negatively associated with V 45Gy and V 50Gy of GTV (both P<0.05). The ventrodorsal motion was negatively correlated with D 98% of uterus ( P<0.05). The left-right motion of Plan 2 was negatively correlated with D 2% of CTV and V 50Gy of uterus (both P<0.05). The head-foot motion was negatively associated with D 98% of CTV, and D 98%, D mean, V 45Gy and V 50Gy of uterus (all P<0.05). The ventrodorsal motion was negatively correlated with D 98% of CTV, D 98%, D mean, V 45Gy and V 50Gy of uterus, and D mean and V 45Gy of GTV (all P<0.05). Conclusions:In intensity-modulated radiotherapy for cervical cancer, the uterine body displacement is large and the low CTV area is mainly located in the uterine body. IGRT can significantly reduce the dosimetric deviation induced by organ movement.

Objective: To study the expression of Wnt2b protein and the epithelial-mesenchymal transition related markers in tissues of carcinoma of bile duct and normal bile duct to determine the clinical significance. The relationships between the expression levels and clinicopathological characteristics were analyzed, and the correlation between Wnt2b and epithelial interstitial transformation (EMT), tumor invasion and metastasis were studied. Methods: A total of 60 patients with cholangiocarcinoma and 30 patients with normal bile duct tissues admitted to the Affiliated Hospital of Qingdao University from December 2008 to December 2013 were studied. The expressions of Wnt2b, E-cadherin and Vimentin protein were detected by SP immunohistochemical staining. The patients were classified according to the expressions of these proteins. Analyses were conducted on the relationships of these proteins with clinical characteristics of the patients with cholangiocarcinoma. Results: The positive expression rate of Wnt2b protein in carcinoma of bile duct tissues was 90.0%, which was significantly higher than that in normal bile duct tissues (χ²=38.1, P<0.05). The positive expression rate of Wnt2b in T₃ + T₄ was significantly higher than that in T₁ + T₂ (P<0.05). There were no correlations of the expression with patients’ age, gender, tumor location and degree of tumor differentiation (P>0.05). Patients with lymph node metastasis had a significantly higher positive expression of Vimentin than patients with no lymph node metastasis, and the loss of E-cadherin expression was increased (all P<0.05). There were no relationship of the expressions of these proteins with patients’ age, gender, tumor location and degree of tumor differentiation (P>0.05). The increased expression of Wnt2b in bile duct cancer cells was related to increase in EMT marker of the positive expression of vimentin and the loss of E-cadherin expression (both P<0.05). Conclusions Wnt2b protein overexpression in cholangiocarcinoma correlated with epithelial-mesenchymal transition related markers. The Wnt2b protein was correlated with cholangiocarcinoma occurrence, development, invasion and metastasis. Wnt2b has the potential to develop into a new therapeutic target for carcinoma of bile duct.

Purpose To investigate the expression of cell cycle related protein including Cyclin D1,CDK4,p16 and IgH/CCND1 fusion gene in mantle cell lymphoma (MCL) and their relationship with each other.Methods The expression of cell cycle related protein including Cyclin D1,CDK4,p16 and IgH/CCND1 fusion gene were detected on the 40 cases of MCL (expreimental group) and 20 cases of reactive hyperplasia (control group) by using the combined detection of fluorescence in situ hybridization (FISH) and immunohistochemistry of EnVision two methods.40 cases of MCL were confirmend by using gene rearrangement technique and immunohistochemistry.The threshold of IgH/CCND1 fusion gene of MCL was established in the control group.Results In the experimental group,Cyclin D1 protein positive expression rate was 100％,the positive expression of CDK4 protein rate was 87.50％,p16 protein positive expression rate was 17.50％.Positive rate of IgH/CCND1 fusion gene of 100％.These cell cycle related protein and IgH/CCND1 fusion gene were negative in the control group.Conclusion In MCL,Cyclin D1-CDK4-p16 pathway is consistent with the principle of tumor cell cycle regulation.The establishment of threshold value of IgH/CCND1 fusion gene by FISH technique may provide the basis for the judgement of FISH of the IgH/CCND1 in China.