1.Heart-sparing strategy for breast cancer radiotherapy based on nnU-Net: regional optimization and automatic segmentation
Jinghan HUANG ; Maidina BATUER ; Chuanghui ZHOU ; Zhi ZHANG ; Limei DENG ; Yuan XU ; Junyuan ZHONG ; Linghong ZHOU ; Xia LI ; Genggeng QIN
Chinese Journal of Radiation Oncology 2025;34(4):355-362
Objective:To investigate the feasibility and optimal expansion width of replacing the left anterior descending coronary artery (LADCA) with the region of heart sparing (RHS) to reduce cardiac radiation dose during breast cancer radiotherapy.Methods:Retrospective analysis was conducted on data from 88 patients with left-sided breast cancer who underwent radiotherapy at 2 centers: Nanfang Hospital of Southern Medical University (50 cases for the training set, 15 cases for the internal test set) and Ganzhou Hospital of Nanfang Hospital (23 cases for the external test set) from March 2022 to January 2024. All patients had left-sided invasive ductal carcinoma with axillary lymph node metastasis, and had undergone modified radical mastectomy and chemotherapy. Based on simulation CT images, 2 radiation oncologists delineated the LADCA and 8 RHSs. The RHSs were delineated by expanding the LADCA contour by 0.5 cm increments, totaling 8 expansions. The RHS widths were defined as 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 cm. The nnU-Net model was trained for 3D automatic segmentation of the LADCA and RHSs. Model performance was evaluated using the Dice similarity coefficient (DSC), relative volume error (RVE), sensitivity, specificity, and 95% Hausdorff distance (HD95). Additionally, the minimum, maximum, and average relative dose variations (RDV) as well as V5% and V20% indicators were calculated for the LADCA and each RHS. Correlation analysis was performed using the least squares regression, with the slope and coefficient of determination ( R2) employed to evaluate the accuracy of the model fitting, the relationship between the LADCA and RHS, and the degree of their correlation, thereby assessing the substitutive effect of the RHS for the LADCA. Results:The DSC for the LADCA was 0.415, while the DSCs for RHS widths of 0.5 cm and 4.0 cm were 0.718 and 0.835, respectively. Overall, the automatic segmentation performance improved with increasing RHS width. The DSC, RVE, sensitivity, specificity, and HD95 for the external test set were largely consistent with those of the internal test set, demonstrating the model's good robustness across different datasets. All RDVmin values were negative, while RDVmax and RDVmean showed a positive correlation with RHS width. RDVmean increased from 39.01% to 75.89% as the RHS width increased. In the correlation analysis, the slopes for RHS widths of 1.5 cm and 2.0 cm were 0.95 and 1.05, respectively, with R2 values and coefficients of variation of 0.79 and 0.73, and 21.11% and 24.03%, respectively. Conclusions:The automatic segmentation model trained on nnU-Net can accurately segment RHSs. Based on geometric and dosimetric indicators, a 1.5 cm-wide RHS is the most suitable substitute for the LADCA, effectively limiting the radiation dose to the LADCA without compromising target dose coverage.
2.Effect of circHIPK2 on angiotensin Ⅱ-induced apoptosis of vascular endothelial cells through regulation of the miR-7-5p/TCF4 axis
Jun GU ; Weidong REN ; Huixian LI ; Wenjuan DENG ; Limei HU ; Huiying LIU ; Yu CAI
Journal of China Medical University 2025;54(3):257-261,267
Objective To investigate the effect of circRNA-homeodomain-interacting protein kinase 2(circHIPK2)on angiotensinⅡ(AngⅡ)-induced apoptosis of vascular endothelial cells through the regulation of the miR-7-5p/transcription factor 4(TCF4)axis.Methods Human umbilical vein endothelial cells(HUVECs)were randomly divided into the control,model,negative control cotrans-fection,circHIPK2 knockdown,miR-7-5p overexpression,and circHIPK2 knockdown+miR-7-5p knockdown groups.Except for the control group,all other groups were administered 10 nmol/L Ang Ⅱ to establish a hypertensive injury model.The circHIPK2,miR-7-5p,and TCF4 mRNA expression levels were detected after transfection.Apoptosis,proliferation,mitochondrial membrane potential,reactive oxygen species(ROS),antioxidant enzymes,pro-inflammatory factors,and TCF4 protein expression were assessed.Results Compared with the control group,the expressions of circHIPK2 and TCF4 mRNA,cell apoptosis rate,relative expression of ROS,levels of IL-6,IL-1β,and IL-18,and expressions of Bax and TCF4 protein increased,and cell viability,miR-7-5p mRNA expression,mitochondrial mem-brane potential,activities of superoxide dismutase(SOD)and catalase(CAT),and Bcl-2 protein expression decreased in the model group(P<0.05).Both circHIPK2 knockdown and miR-7-5p overexpression reversed Ang Ⅱ-induced pathological changes in vascular endothelial cells.miR-7-5p knockdown reduced the effect of circHIPK2 knockdown on pathological cellular changes in the model group.Conclusion circHIPK2 knockdown can weaken TCF4 expression by upregulating miR-7-5p,thereby reducing Ang Ⅱ-induced inflam-mation and oxidative stress in vascular endothelial cells and ultimately inhibiting cell apoptosis.
3.Effect of circHIPK2 on angiotensin Ⅱ-induced apoptosis of vascular endothelial cells through regulation of the miR-7-5p/TCF4 axis
Jun GU ; Weidong REN ; Huixian LI ; Wenjuan DENG ; Limei HU ; Huiying LIU ; Yu CAI
Journal of China Medical University 2025;54(3):257-261,267
Objective To investigate the effect of circRNA-homeodomain-interacting protein kinase 2(circHIPK2)on angiotensinⅡ(AngⅡ)-induced apoptosis of vascular endothelial cells through the regulation of the miR-7-5p/transcription factor 4(TCF4)axis.Methods Human umbilical vein endothelial cells(HUVECs)were randomly divided into the control,model,negative control cotrans-fection,circHIPK2 knockdown,miR-7-5p overexpression,and circHIPK2 knockdown+miR-7-5p knockdown groups.Except for the control group,all other groups were administered 10 nmol/L Ang Ⅱ to establish a hypertensive injury model.The circHIPK2,miR-7-5p,and TCF4 mRNA expression levels were detected after transfection.Apoptosis,proliferation,mitochondrial membrane potential,reactive oxygen species(ROS),antioxidant enzymes,pro-inflammatory factors,and TCF4 protein expression were assessed.Results Compared with the control group,the expressions of circHIPK2 and TCF4 mRNA,cell apoptosis rate,relative expression of ROS,levels of IL-6,IL-1β,and IL-18,and expressions of Bax and TCF4 protein increased,and cell viability,miR-7-5p mRNA expression,mitochondrial mem-brane potential,activities of superoxide dismutase(SOD)and catalase(CAT),and Bcl-2 protein expression decreased in the model group(P<0.05).Both circHIPK2 knockdown and miR-7-5p overexpression reversed Ang Ⅱ-induced pathological changes in vascular endothelial cells.miR-7-5p knockdown reduced the effect of circHIPK2 knockdown on pathological cellular changes in the model group.Conclusion circHIPK2 knockdown can weaken TCF4 expression by upregulating miR-7-5p,thereby reducing Ang Ⅱ-induced inflam-mation and oxidative stress in vascular endothelial cells and ultimately inhibiting cell apoptosis.
4.Heart-sparing strategy for breast cancer radiotherapy based on nnU-Net: regional optimization and automatic segmentation
Jinghan HUANG ; Maidina BATUER ; Chuanghui ZHOU ; Zhi ZHANG ; Limei DENG ; Yuan XU ; Junyuan ZHONG ; Linghong ZHOU ; Xia LI ; Genggeng QIN
Chinese Journal of Radiation Oncology 2025;34(4):355-362
Objective:To investigate the feasibility and optimal expansion width of replacing the left anterior descending coronary artery (LADCA) with the region of heart sparing (RHS) to reduce cardiac radiation dose during breast cancer radiotherapy.Methods:Retrospective analysis was conducted on data from 88 patients with left-sided breast cancer who underwent radiotherapy at 2 centers: Nanfang Hospital of Southern Medical University (50 cases for the training set, 15 cases for the internal test set) and Ganzhou Hospital of Nanfang Hospital (23 cases for the external test set) from March 2022 to January 2024. All patients had left-sided invasive ductal carcinoma with axillary lymph node metastasis, and had undergone modified radical mastectomy and chemotherapy. Based on simulation CT images, 2 radiation oncologists delineated the LADCA and 8 RHSs. The RHSs were delineated by expanding the LADCA contour by 0.5 cm increments, totaling 8 expansions. The RHS widths were defined as 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 cm. The nnU-Net model was trained for 3D automatic segmentation of the LADCA and RHSs. Model performance was evaluated using the Dice similarity coefficient (DSC), relative volume error (RVE), sensitivity, specificity, and 95% Hausdorff distance (HD95). Additionally, the minimum, maximum, and average relative dose variations (RDV) as well as V5% and V20% indicators were calculated for the LADCA and each RHS. Correlation analysis was performed using the least squares regression, with the slope and coefficient of determination ( R2) employed to evaluate the accuracy of the model fitting, the relationship between the LADCA and RHS, and the degree of their correlation, thereby assessing the substitutive effect of the RHS for the LADCA. Results:The DSC for the LADCA was 0.415, while the DSCs for RHS widths of 0.5 cm and 4.0 cm were 0.718 and 0.835, respectively. Overall, the automatic segmentation performance improved with increasing RHS width. The DSC, RVE, sensitivity, specificity, and HD95 for the external test set were largely consistent with those of the internal test set, demonstrating the model's good robustness across different datasets. All RDVmin values were negative, while RDVmax and RDVmean showed a positive correlation with RHS width. RDVmean increased from 39.01% to 75.89% as the RHS width increased. In the correlation analysis, the slopes for RHS widths of 1.5 cm and 2.0 cm were 0.95 and 1.05, respectively, with R2 values and coefficients of variation of 0.79 and 0.73, and 21.11% and 24.03%, respectively. Conclusions:The automatic segmentation model trained on nnU-Net can accurately segment RHSs. Based on geometric and dosimetric indicators, a 1.5 cm-wide RHS is the most suitable substitute for the LADCA, effectively limiting the radiation dose to the LADCA without compromising target dose coverage.
5.Quantitative evaluation of left and right atrial function and its difference in normal fetus during middle and late pregnancy using two-dimensional speckle tracking echocardiography
Limei ZHOU ; Bowen ZHAO ; Mei PAN ; Xiaohui PENG ; Ran CHEN ; Mingming MA ; Yuanshi TIAN ; Yan DENG
Chinese Journal of Ultrasonography 2024;33(8):659-666
Objective:To explore the potential application of two-dimensional speckle tracking echocardiography (2D-STE) in terms of quantification and evaluating left and right atrial function in normal fetuses, and to investigate the relevant factors affecting left and right atrial function in normal fetuses as well as differences between both atrial function.Methods:A total of 100 single fetuses underwent fetal echocardiography in the Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine from January 2019 to October 2022 were retrospectively enrolled. The standard basal or apical four-chamber view clips were obtained, and the left and right atrial function were quantitatively analyzed using TomTec-ARENA off-line cardiac analysis software for quantitative assessment of both atrial strain measurements including left atrial reservoir phase longitudinal strain (LASr), left atrial ductal phase longitudinal strain (LAScd), left atrial systolic phase longitudinal strain (LASct), right atrial reservoir phase longitudinal strain (RASr), right atrial ductal phase longitudinal strain (RAScd), right atrial systolic phase longitudinal strain (RASct), and the ratio of systolic longitudinal strain to conduit longitudinal strain in left and right atrial systolic display groups were calculated which was denoted as Sct/Scd.Routine fetal obstetric ultrasound measurements and fetal echocardiographic parameters in the two groups were obtained including fetal heart rate (FHR), left atrial end-systolic length (LAESL), left atrial end-systolic diameter (LAESD), left atrial end-systolic area (LAESA), left ventricular end-diastolic transverse diameter (LVEDD), right atrial end-systolic length (RAESL), right atrial end-systolic diameter (RAESD), right atrial end-systolic area (RAESA), right ventricular end-diastolic transverse diameter (RVEDD), peak blood flow velocity of mitral valve and tricuspid valve in early and late diastolic period (E, A), peak ratio of E and A: E/A (MV), E/A (TV), and the difference between the left and right atrial strain indices and the routine fetal obstetric ultrasound and fetal echocardiographic parameters, as well as the correlation between the above parameters and gestational age were analyzed. The repeatability tests were performed using the intra-class correlation coefficientt (ICC).Results:Significant differences were found in LASr and RASr, LAScd and RAScd, LASct and LAScd, Sct/Scd between the left atrium and right atrium, E/A (MV) and E/A (TV), LAESD and RAESD, LAESL and RAESL (all P<0.05), there was significant difference in FHR between the left atrial contraction display group and the no atrial contraction display group ( P=0.011), no significant difference in other parameters (all P>0.05). Correlation analysis showed that, LASr, LASct, RASr, and RASct showed moderate negative correlation with gestational age ( rs=-0.570, -0.601, -0.469, -0.568; all P<0.001). While LAScd, RAScd, E/A (MV), E/A (TV) were moderately positively related with gestational age ( rs=0.310, 0.350, 0.330, 0.343; all P<0.05). LAESL, LAESD, LAESA, RAESL, RAESD, RAESA, LVEDD and RVEDD were significantly positively related with gestational age ( rs=0.662, 0.768, 0.792, 0.728, 0.828, 0.822, 0.838, 0.802, all P<0.001). The inter-examiner ICC of fetal LASr and RASr were 0.89 and 0.84 (both P<0.05) and the intra-examiner ICC of fetal RASr and LASr both were 0.80 (both P<0.05), with good consistency. Conclusions:2D-STE is highly feasible and reproducible in assessing fetal atrial function. The corresponding variation values of fetal atria at different gestational weeks were obtained in this study, which provides a new reference index for us to further study normal fetal atria as well as comparative analysis of fetal cardiac function under prenatal pathological conditions.
6.DANCR Regulates hESC Differentiation Towards Definitive Endoderm
Jiacheng DENG ; Limei PENG ; Yingpeng SHI ; Xiaomin ZHONG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(1):45-53
ObjectiveTo explore the function of DANCR during the differentiation of human embryonic stem cells (hESC) toward definitive endoderm (DE). MethodsThe in vitro DE differentiation system was established and its efficiency was verified. The correlation between the expression level of DANCR and DE differentiation process was detected. Using lentivirus system, we stably knocked down DANCR in hESC. The shDANCR hESC line was applied to DE differentiation, using qPCR and Western blot to detect the expression of DE marker genes SOX17 and FOXA2, and that of primitive streak marker genes Brachyury (T), EOMES, MIXL1 and GSC. Dual luciferase reporter assay and qPCR were used to confirm the interaction between DANCR and the WNT pathway during DE differentiation. ResultsThe in vitro differentiation system mimicked DE differentiation efficiently. And the expression of DANCR was gradually downregulated during differentiation. DANCR was efficiently knocked down in the shDANCR hESC line (P < 0.001). Compared with those in the control group, the expression levels of primitive markers Brachyury (T), EOMES, MIXL1 and GSC, as well as DE markers SOX17 and FOXA2, were significantly decreased in shDANCR groups (P < 0.05). Furthermore, the transcriptional activity of the WNT pathway in shDANCR groups was lower than that in the control group (P < 0.05). And RNA levels of downstream genes of the WNT pathway, FZD5, FZD8, SFRP1, FRZB and ANKRD6, were significantly decreased in shDANCR groups (P < 0.05). However, differences in protein levels of the TGFβ pathway effectors SMAD2/3 and p-SMAD2 were statistically insignificant in shDANCR and control groups (P > 0.05). Forced activation of β-CATENIN rescued DANCR knock down-induced deficiency in DE differentiation. ConclusionsThe expression of DANCR decreases during DE differentiation. DANCR may promote DE differentiation through modulating the activity of the WNT pathway.
7.Policy evolution and development suggestions of patient medical experience in China
Xia LIN ; Limei CHEN ; Songtao DENG ; Yanran SONG ; Benyan LI ; Xinxin CAO ; Hongyun WANG ; Lanting LYU ; Hu CHEN
Chinese Journal of Hospital Administration 2024;40(11):832-837
In 2023, the National Health Commission and the National Administration of Traditional Chinese Medicine jointly issued the " Notice on carrying out the theme activity to improve medical experience and enhance patient experience", China has entered a new stage of development in the field of medical service improvement. This study, through literature research, sorted out the evolution of China′s patient medical experience-related policies and the shift in concept from satisfaction to medical experience. It divided the historical evolution of patient medical experience policies into four periods: the exploration period, the development period, the policy improvement period, and the new policy implementation period, based on the implementation of reform and opening up, the introduction of new medical reforms, and the proposal of the " theme activity" in 2023. From May to August 2023, interviews were conducted with 20 experts in the field of health management, 20 clinical doctors, and 20 inpatients to discuss China′s experience, deficiencies, and suggestions for improving patient medical experience. Based on the interview materials, this study summarized China′s experience and deficiencies in enhancing patient medical experience from aspects such as resources, systems, concepts, and human resources. It suggested adjusting the structure and layout of medical resources to enhance the balance of high-quality medical resource allocation; establishing a comprehensive evaluation system for patient medical experience; increasing the attention and conceptual understanding of health administrative departments and medical institutions at all levels to optimize patient medical experience, and improving the formulation and connection of supporting policies; caring for medical staff and fully mobilizing their initiative to enhance patient experience, in order to continuously improve patient medical experience.
8.Analysis of factors influencing patients′ medical experience based on grounded theory
Xia LIN ; Benyan LI ; Songtao DENG ; Yanran SONG ; Xinxin CAO ; Limei CHEN ; Hongyun WANG ; Lanting LYU ; Xiaona DAI ; Hu CHEN
Chinese Journal of Hospital Administration 2024;40(11):838-843
Objective:To analyze the factors influencing patients′ medical experience, to provide reference for medical institutions to improve patients′ medical experience.Methods:A stratified sampling method was employed nationwide to select 32 patients and 20 medical staff. From May to August 2023, semi-structured interviews were conducted with them regarding the factors influencing patients′ medical experience. The data from the interviews were analyzed using programmed grounded theory, which led to the identification of factors affecting patients′ medical experience.Results:After three-level coding, four main categories of demographic characteristics, self health characteristics, medical outcome experience, and medical process experience, two core categories of patient related influencing factors and hospital related influencing factors were obtained. Additionally were also obtained.Conclusions:The factors influencing patients′ medical experience are multifaceted and jointly dominated by multiple stakeholders. Medical institutions should adopt a variety of measures to continuously improve patients′ medical experience. When assessing patients′ medical experience, the impact of individual differences among patients on the assessment results should be fully considered.
9.Policy evolution and development suggestions of patient medical experience in China
Xia LIN ; Limei CHEN ; Songtao DENG ; Yanran SONG ; Benyan LI ; Xinxin CAO ; Hongyun WANG ; Lanting LYU ; Hu CHEN
Chinese Journal of Hospital Administration 2024;40(11):832-837
In 2023, the National Health Commission and the National Administration of Traditional Chinese Medicine jointly issued the " Notice on carrying out the theme activity to improve medical experience and enhance patient experience", China has entered a new stage of development in the field of medical service improvement. This study, through literature research, sorted out the evolution of China′s patient medical experience-related policies and the shift in concept from satisfaction to medical experience. It divided the historical evolution of patient medical experience policies into four periods: the exploration period, the development period, the policy improvement period, and the new policy implementation period, based on the implementation of reform and opening up, the introduction of new medical reforms, and the proposal of the " theme activity" in 2023. From May to August 2023, interviews were conducted with 20 experts in the field of health management, 20 clinical doctors, and 20 inpatients to discuss China′s experience, deficiencies, and suggestions for improving patient medical experience. Based on the interview materials, this study summarized China′s experience and deficiencies in enhancing patient medical experience from aspects such as resources, systems, concepts, and human resources. It suggested adjusting the structure and layout of medical resources to enhance the balance of high-quality medical resource allocation; establishing a comprehensive evaluation system for patient medical experience; increasing the attention and conceptual understanding of health administrative departments and medical institutions at all levels to optimize patient medical experience, and improving the formulation and connection of supporting policies; caring for medical staff and fully mobilizing their initiative to enhance patient experience, in order to continuously improve patient medical experience.
10.Analysis of factors influencing patients′ medical experience based on grounded theory
Xia LIN ; Benyan LI ; Songtao DENG ; Yanran SONG ; Xinxin CAO ; Limei CHEN ; Hongyun WANG ; Lanting LYU ; Xiaona DAI ; Hu CHEN
Chinese Journal of Hospital Administration 2024;40(11):838-843
Objective:To analyze the factors influencing patients′ medical experience, to provide reference for medical institutions to improve patients′ medical experience.Methods:A stratified sampling method was employed nationwide to select 32 patients and 20 medical staff. From May to August 2023, semi-structured interviews were conducted with them regarding the factors influencing patients′ medical experience. The data from the interviews were analyzed using programmed grounded theory, which led to the identification of factors affecting patients′ medical experience.Results:After three-level coding, four main categories of demographic characteristics, self health characteristics, medical outcome experience, and medical process experience, two core categories of patient related influencing factors and hospital related influencing factors were obtained. Additionally were also obtained.Conclusions:The factors influencing patients′ medical experience are multifaceted and jointly dominated by multiple stakeholders. Medical institutions should adopt a variety of measures to continuously improve patients′ medical experience. When assessing patients′ medical experience, the impact of individual differences among patients on the assessment results should be fully considered.

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