Objective:To explore the impact of baseline remnant cholesterol levels at a single time point and cumulative remnant cholesterol exposure on the progression trajectories of arterial stiffness.Methods:This prospective cohort study included 2 401 eligible participants from the Beijing Health Management Cohort who consecutively attended health examinations in 2010-2011, 2012-2013, and 2014-2015. The remnant cholesterol value measured in 2014-2015 served as the baseline remnant cholesterol level at a single time point. The cumulative exposure indices were calculated based on remnant cholesterol values from three health examinations from 2010 to 2015, including cumulative exposure, cumulative exposure burden, and duration of high remnant cholesterol exposure. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). The follow-up continued until December 31, 2019, with annual check-ups. During the follow-up period, a group-based trajectory model was employed to construct the progression trajectories of baPWV. The associations between the baseline remnant cholesterol level, cumulative exposure indices of remnant cholesterol and baPWV trajectories were examined using ordinal logistic regression models, adjusting for traditional cardiovascular risk factors and low-density lipoprotein cholesterol (LDL-C) levels.Results:The age of the 2 401 participants was 61 (54, 69) years, with 1 801 (75.01%) being male. The group-based trajectory model indicated that the best-fit model categorized the participants into three subgroups: low-rising group (1 036 individuals, 43.15%), moderate-rising group (1 137 individuals, 47.36%), and high-rising group (228 individuals, 9.50%). After adjusting for traditional cardiovascular risk factors, baseline remnant cholesterol levels at a single point ( OR=1.170, 95% CI: 1.074-1.274), cumulative remnant cholesterol exposure ( OR=1.194, 95% CI: 1.096-1.303), cumulative remnant cholesterol exposure burden ( OR=1.270, 95% CI: 1.071-1.507), and high-remnant cholesterol exposure duration (6 years: OR=1.351, 95% CI: 1.077-1.695) were significantly associated with the risk of developing a poor baPWV progression trajectory. These results remained significant after adjusting for cumulative average LDL-C levels. The association between baseline remnant cholesterol levels and baPWV progression became insignificant after adjusting for cumulative remnant cholesterol levels ( OR=1.053, 95% CI: 0.923-1.197), while the association between cumulative remnant cholesterol exposure and baPWV progression remained significant after adjusting for baseline remnant cholesterol levels ( OR=1.145, 95% CI: 1.008-1.305). Conclusions:Higher levels of baseline remnant cholesterol and cumulative remnant cholesterol are independent risk factors for the progression of arterial stiffness. These associations remain significant even after adjusting for traditional cardiovascular risk factors and LDL-C levels. Furthermore, the effect of cumulative remnant cholesterol levels on the progression of arterial stiffness was stronger than the effect of baseline remnant cholesterol levels.

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

Background Evidence about the association between air pollution and carotid intima-media thickness (CIMT) is inconsistent, and limited studies have explored the relationship between gaseous pollutants and CIMT. Additionally, personal activity patterns and infiltrated ambient pollution are not comprehensively considered to estimate individual exposure to air pollutants. Objective To investigate the relationship between long-term time-weighted individual exposure to ambient pollutants [fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), nitrogen dioxide (NO₂), sulfur dioxide (SO₂), ozone (O₃), and carbon monoxide (CO)] and the progression of CIMT. Methods This study was performed among 554 participants in the Beijing Health Management Cohort who were free of atherosclerotic lesions on carotid artery at baseline. Daily concentrations of pollutants were predicted at both residential and work addresses based on land-use regression model. With additional consideration of personal indoor and outdoor activity patterns at both addresses and exposure to ambient pollutants from traffic transportation, individual time-weighted concentration was calculated. Indoor exposure was estimated by infiltrated ambient pollutants (based on infiltration factors and land-use regression model). Personal activity patterns included type, time, location, and frequency. Exposure to ambient pollutants from different traffic transportations was estimated by the average outdoor pollutant concentrations at both residential and work addresses combined within filtration factors and time spent on commuting. Multiple linear regression was conducted to assess the association of time-weighted individual pollutant exposure and the central position of CIMT progression. Quantile regression was applied to explore the relationship between time-weighted individual pollutant exposure and the progression of CIMT on different percentiles. Results The median value of CIMT progression was 369.49 μm·year⁻¹. PM_2.5, PM₁₀, SO₂, and O₃ were associated with CIMT progression in the multiple linear regression model. The largest effect sizes of PM_2.5, PM₁₀, and SO₂ were obtained for one-year exposure (regression coefficient: 66.910, 64.077, and 191.070, respectively), and two-year exposure for O₃ (regression coefficient: 62.197). The results of quantile regression demonstrated different effect sizes for pollutants among different percentiles on CIMT progression. Significant associations between CIMT progression and PM_2.5 from P₃₀ to P₅₀, CO from P₁₀ to P₄₀, and PM₁₀ from P₃₀ to P₆₀ were observed. Two-year and three-year exposures to NO₂ (P₁₀, P₂₀ and P₄₀) were also associated with CIMT progression. The association between SO₂ and the progression of CIMT was proved on all percentiles, and larger effect sizes of one-year and two-year exposures to SO₂ (except P₉₀) were demonstrated with increasing percentiles. The upward trend for the coefficients was clearly presented from P₅₀ to P₈₀. Specifically, the coefficient of two-year exposure to SO₂ ranged from 136.583 (P₅₀) to 277.330 (P₈₀). No statistically significant association was observed between O₃ and CIMT progression on any percentile (P>0.05), and the results were inconsistent with those of the multiple linear regression. Conclusion Individual time-weighted exposures to PM_2.5, PM₁₀, SO₂, NO₂, and CO have the potential to promote the progression of CIMT, and the adverse effect of ambient pollution on atherosclerotic lesion is identified.

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 help clinicians simplify the post-processing operations of structures by developing rapid processing software for target area and organs at risk structures based on ESAPI.Methods:SmartStructure script software was developed based on ESAPI, verified and evaluated in clinical work. 10 cases of rectal cancer receiving neoadjuvant radiotherapy, 10 breast cancer treated with postoperative radiotherapy, 10 cervical cancer receiving postoperative radiotherapy, 10 nasopharyngeal carcinoma receiving radical radiotherapy and 10 lung stereotactic body radiotherapy (SBRT) were selected, and different types of tumors had different post-processing operations of structures. In each case, three methods were used for post-processing of structures. In the control group (manual group), normal manual processing was employed. In the experimental group 1(SmaStru-N group), scripts without templates were utilized. In the experimental group 2(SmaStru-P group). scripts combined with templates were adopted. The processing time of the three methods was compared. Clinicians scored the scripting software from multiple aspects and compared the feeling scores of scripting software and manual operation.Results:All three methods can be normally applied in clinical settings. The error rate in the manual group was 7.0%, 3.0% in the SmaStru-N group 0% in the SmaStru-P group, respectively. Compared with the manual method, SmaStru-N shortened the processing time of target area and organs at risk by 60.9% and 93.3% for SmaStru-P. In addition, SmartStructure was superior to manual method in terms of using feeling scores. Clinicians gave lower score for the" applicability" and" simplicity" , and higher score on the" accuracy" and" efficiency" .Conclusions:Compared with conventional manual structure processing method, SmartStructure software can rapidly and accurately process all structures of the target area and organs at risk, and its advantages become more obvious with the increasing number of structures that need to be processed. SmartStructure software can meet clinical requirements, reduce the error rate, elevate processing speed, improve the working efficiency of clinicians, providing basis for the development of adaptive radiotherapy.

Objective To analyze the effect of image guidance on the doses to the rectum and bladder in radical external beam radiotherapy for cervical cancer, and to investigate the reasonable application mode of image-guided radiotherapy (IGRT) in the treatment of cervical cancer. Methods A total of 20 patients with cervical cancer who underwent helical tomotherapy(HT) in PLA Army General Hospital from 2012 to 2016 were enrolled in this study. A megavoltage computed tomography(MVCT) scan was performed before each treatment. The obtained MVCT images were used for dose reconstruction in the adaptive module of HT to obtain the actual dose (Plan-1) and the non-image-guided dose was simulated (Plan-2). Each single dose distribution and the corresponding fused CT image were sent to the software MIM 6.0 to obtain the total radiation dose by dose superposition. The radiation doses and volumes of the rectum and bladder were compared between the two therapeutic plans. Results The radiation doses to the rectum and bladder in Plan-2 were significantly higher than those in Plan-1. There were significant differences in Dmaxand V50of the rectum and V50of the bladder between Plan-1 and Plan-2(P=0.040;P=0.000;P=0.047). Compared with Plan-1, there were statistical differences in inter-fractional Dmaxand V50during the initial treatment (P=0.047,0.037), and V50of the rectum within the 13thto 21stradiotherapy, respectively (P=0.009, 0.017, 0.028). Besides, differences regarding Vmaxand V50in the initial treatment and the 21stto 23rdradiotherapy were close to the statistical significance when compared to those in Plan-1, respectively (P= 0.061,0.053; P= 0.072,0.058). Conclusions IGRT can reduce the radiation doses and volumes of the rectum and bladder, especially the rectum. The therapeutic plan should be rescheduled when tumor retraction is evident at half of the total radiation dose (around 13thfraction) in external beam radiotherapy. If it is difficult to achieve image guidance in each treatment,selective image guidance could be performed to effectively reduce the injuries of the rectum and bladder.