1.Impacts of PIM2/PFKFB3 signaling pathway-mediated enhancement of glycolysis in pancreatic cancer cells on the anticancer capacity of radiotherapy
Yufen LUAN ; Judong LUO ; Renming WAN ; Guangyu LI ; Guanglei FAN
Chinese Journal of Radiological Medicine and Protection 2025;45(10):949-957
Objective:To explore the impacts of 131I-NaI radiotherapy on the promotion of glycolysis and 18F-fluorodeoxyglucose ( 18F-FDG) uptake in pancreatic cancer cells via the induction of proviral integration moloney murineleukemia virus 2 (PIM2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3). Methods:In the cell experiments, human pancreatic carcinoma cells-1 (PANC-1) were randomly divided into four groups: a control group, an HJ-PI01 group, a 131I-NaI group, and an HJ-PI01 + 131I-NaI group. Their aerobic glycolysis capacity was assessed by measuring glucose uptake, lactate production, and extracellular acidification rate (ECAR). In vivo animal experiments, 12 nu/nu female nude mice were given 100 μl (1 × 10 7 cells) of cell suspension through subcutaneous injection into the left lower limbs. When the tumor volume reached approximately 60 mm 3, these mice were divided into four groups (a control group, a HJ-PI01 group, a 131I-NaI group, and an HJ-PI01+ 131I-NaI group) using a random number table, with three mice in each group. After 14 days of treatment, 18F-FDG PET/CT imaging was performed to calculate the maximum standardized uptake value (SUV max) of the xenografts. Following PET/CT imaging, the tumor tissues were harvested and analyzed for PIM2, PFKFB3, and Ki-67 expressions using immunohistochemistry. Results:In cell experiments, compared to the control group, the HJ-PI01 group exhibited significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR in PANC-1 cells ( t = 4.59-13.98, P < 0.05). In contrast, the 131I-NaI group showed significant increases in these parameters ( t = 3.36-13.97, P < 0.05). Compared to the 131I-NaI group, the HJ-PI01+ 131I-NaI group showed significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR ( t = 5.14-20.87, P < 0.05). In the animal experiments, compared to the control group, the three groups displayed significant decrease in SUV max of 18F-FDG uptake in tumors ( t = 16.48, 22.49, 32.64, P < 0.001). Moreover, the HJ-PI01 + 131I-NaI group exhibite significantly lower SUV max than the 131I-NaI group ( t = 10.16, P < 0.001). Immunohistochemical analysis revealed that the HJ-PI01+ 131I-NaI group, compared to the 131I-NaI group, showed significantly lower Ki-67 expression and the PIM2/PFKFB3 signaling pathway in tumor tissues ( t = 3.27, 10.73, 14.85, P < 0.05). Conclusions:Glycolysis enhancement of PANC-1 cells, mediated by the PIM2/PFKFB3 signaling pathway inhibition, can significantly improve the anticancer capacity of 131I-NaI, providing a novel strategy for radiotherapy in pancreatic cancer.
2.Impacts of PIM2/PFKFB3 signaling pathway-mediated enhancement of glycolysis in pancreatic cancer cells on the anticancer capacity of radiotherapy
Yufen LUAN ; Judong LUO ; Renming WAN ; Guangyu LI ; Guanglei FAN
Chinese Journal of Radiological Medicine and Protection 2025;45(10):949-957
Objective:To explore the impacts of 131I-NaI radiotherapy on the promotion of glycolysis and 18F-fluorodeoxyglucose ( 18F-FDG) uptake in pancreatic cancer cells via the induction of proviral integration moloney murineleukemia virus 2 (PIM2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3). Methods:In the cell experiments, human pancreatic carcinoma cells-1 (PANC-1) were randomly divided into four groups: a control group, an HJ-PI01 group, a 131I-NaI group, and an HJ-PI01 + 131I-NaI group. Their aerobic glycolysis capacity was assessed by measuring glucose uptake, lactate production, and extracellular acidification rate (ECAR). In vivo animal experiments, 12 nu/nu female nude mice were given 100 μl (1 × 10 7 cells) of cell suspension through subcutaneous injection into the left lower limbs. When the tumor volume reached approximately 60 mm 3, these mice were divided into four groups (a control group, a HJ-PI01 group, a 131I-NaI group, and an HJ-PI01+ 131I-NaI group) using a random number table, with three mice in each group. After 14 days of treatment, 18F-FDG PET/CT imaging was performed to calculate the maximum standardized uptake value (SUV max) of the xenografts. Following PET/CT imaging, the tumor tissues were harvested and analyzed for PIM2, PFKFB3, and Ki-67 expressions using immunohistochemistry. Results:In cell experiments, compared to the control group, the HJ-PI01 group exhibited significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR in PANC-1 cells ( t = 4.59-13.98, P < 0.05). In contrast, the 131I-NaI group showed significant increases in these parameters ( t = 3.36-13.97, P < 0.05). Compared to the 131I-NaI group, the HJ-PI01+ 131I-NaI group showed significant reduction in glucose uptake, lactate production, PFKFB3 protein expression, and ECAR ( t = 5.14-20.87, P < 0.05). In the animal experiments, compared to the control group, the three groups displayed significant decrease in SUV max of 18F-FDG uptake in tumors ( t = 16.48, 22.49, 32.64, P < 0.001). Moreover, the HJ-PI01 + 131I-NaI group exhibite significantly lower SUV max than the 131I-NaI group ( t = 10.16, P < 0.001). Immunohistochemical analysis revealed that the HJ-PI01+ 131I-NaI group, compared to the 131I-NaI group, showed significantly lower Ki-67 expression and the PIM2/PFKFB3 signaling pathway in tumor tissues ( t = 3.27, 10.73, 14.85, P < 0.05). Conclusions:Glycolysis enhancement of PANC-1 cells, mediated by the PIM2/PFKFB3 signaling pathway inhibition, can significantly improve the anticancer capacity of 131I-NaI, providing a novel strategy for radiotherapy in pancreatic cancer.
3.Study on histological features and Bmp4 expression pattern during tooth formation and replacement in Xenopus laevis
Young-Hoon LEE ; Renming GUO ; Yibo LI ; Byung Keon PARK
International Journal of Oral Biology 2024;49(2):48-52
This study explores the histological features and Bmp4 expression patterns in the replaced tooth germ of Xenopus laevis. Tooth germ formation starts from the dental placode through epithelial-mesenchymal interactions, involving various signaling pathways such as Fgf, Shh, Bmp, and Wnt. In mice, Bmp4 expression in the dental placode inhibits Pax9 expression in the dental mesenchyme. Although absent in the presumptive dental lamina of birds and toothless mammals, Bmp4 remains conserved in reptiles and fish owing to gene duplication. However, its expression in amphibian tooth germs is poorly understood. Three-month-old X. laevis were employed in this study. Initially, samples underwent paraffin embedding and were sectioned into 5 or 12 μm ribbons for H&E staining and in situ hybridization, respectively. Results revealed teeth appearing in two maxillary rows: the labial side, with prefunctional and functional teeth, and the lingual side, with replaced tooth germs behind functional teeth. Enameloid was observed between the inner dental epithelium and dental mesenchyme at the cap or early bell stages, whereas enamel and dentin formed during the late bell or mineralization stages from the replaced tooth germ. Bmp4 expression was evident in the inner dental epithelium (ameloblasts), dental papilla (odontoblasts), stellate reticulum, and Hertwig’s epithelial root sheath.Overall, these findings highlight the conservation of Bmp4 expression in X. laevis tooth development.
4.Study on histological features and Bmp4 expression pattern during tooth formation and replacement in Xenopus laevis
Young-Hoon LEE ; Renming GUO ; Yibo LI ; Byung Keon PARK
International Journal of Oral Biology 2024;49(2):48-52
This study explores the histological features and Bmp4 expression patterns in the replaced tooth germ of Xenopus laevis. Tooth germ formation starts from the dental placode through epithelial-mesenchymal interactions, involving various signaling pathways such as Fgf, Shh, Bmp, and Wnt. In mice, Bmp4 expression in the dental placode inhibits Pax9 expression in the dental mesenchyme. Although absent in the presumptive dental lamina of birds and toothless mammals, Bmp4 remains conserved in reptiles and fish owing to gene duplication. However, its expression in amphibian tooth germs is poorly understood. Three-month-old X. laevis were employed in this study. Initially, samples underwent paraffin embedding and were sectioned into 5 or 12 μm ribbons for H&E staining and in situ hybridization, respectively. Results revealed teeth appearing in two maxillary rows: the labial side, with prefunctional and functional teeth, and the lingual side, with replaced tooth germs behind functional teeth. Enameloid was observed between the inner dental epithelium and dental mesenchyme at the cap or early bell stages, whereas enamel and dentin formed during the late bell or mineralization stages from the replaced tooth germ. Bmp4 expression was evident in the inner dental epithelium (ameloblasts), dental papilla (odontoblasts), stellate reticulum, and Hertwig’s epithelial root sheath.Overall, these findings highlight the conservation of Bmp4 expression in X. laevis tooth development.
5.Study on histological features and Bmp4 expression pattern during tooth formation and replacement in Xenopus laevis
Young-Hoon LEE ; Renming GUO ; Yibo LI ; Byung Keon PARK
International Journal of Oral Biology 2024;49(2):48-52
This study explores the histological features and Bmp4 expression patterns in the replaced tooth germ of Xenopus laevis. Tooth germ formation starts from the dental placode through epithelial-mesenchymal interactions, involving various signaling pathways such as Fgf, Shh, Bmp, and Wnt. In mice, Bmp4 expression in the dental placode inhibits Pax9 expression in the dental mesenchyme. Although absent in the presumptive dental lamina of birds and toothless mammals, Bmp4 remains conserved in reptiles and fish owing to gene duplication. However, its expression in amphibian tooth germs is poorly understood. Three-month-old X. laevis were employed in this study. Initially, samples underwent paraffin embedding and were sectioned into 5 or 12 μm ribbons for H&E staining and in situ hybridization, respectively. Results revealed teeth appearing in two maxillary rows: the labial side, with prefunctional and functional teeth, and the lingual side, with replaced tooth germs behind functional teeth. Enameloid was observed between the inner dental epithelium and dental mesenchyme at the cap or early bell stages, whereas enamel and dentin formed during the late bell or mineralization stages from the replaced tooth germ. Bmp4 expression was evident in the inner dental epithelium (ameloblasts), dental papilla (odontoblasts), stellate reticulum, and Hertwig’s epithelial root sheath.Overall, these findings highlight the conservation of Bmp4 expression in X. laevis tooth development.
6.Establishing and validating a spotted tongue recognition and extraction model based on multiscale convolutional neural network
PENG Chengdong ; WANG Li ; JIANG Dongmei ; YANG Nuo ; CHEN Renming ; DONG Changwu
Digital Chinese Medicine 2022;5(1):49-58
Objective In tongue diagnosis, the location, color, and distribution of spots can be used to speculate on the viscera and severity of the heat evil. This work focuses on the image analysis method of artificial intelligence (AI) to study the spotted tongue recognition of traditional Chinese medicine (TCM). Methods A model of spotted tongue recognition and extraction is designed, which is based on the principle of image deep learning and instance segmentation. This model includes multiscale feature map generation, region proposal searching, and target region recognition. Firstly, deep convolution network is used to build multiscale low- and high-abstraction feature maps after which, target candidate box generation algorithm and selection strategy are used to select high-quality target candidate regions. Finally, classification network is used for classifying target regions and calculating target region pixels. As a result, the region segmentation of spotted tongue is obtained. Under non-standard illumination conditions, various tongue images were taken by mobile phones, and experiments were conducted. Results The spotted tongue recognition achieved an area under curve (AUC) of 92.40%, an accuracy of 84.30% with a sensitivity of 88.20%, a specificity of 94.19%, a recall of 88.20%, a regional pixel accuracy index pixel accuracy (PA) of 73.00%, a mean pixel accuracy (mPA) of 73.00%, an intersection over union (IoU) of 60.00%, and a mean intersection over union (mIoU) of 56.00%. Conclusion The results of the study verify that the model is suitable for the application of the TCM tongue diagnosis system. Spotted tongue recognition via multiscale convolutional neural network (CNN) would help to improve spot classification and the accurate extraction of pixels of spot area as well as provide a practical method for intelligent tongue diagnosis of TCM.
7.Preliminary study of stereotactic cardiac radioablation in radiotherapy of ventricular arrhythmia
Jing LI ; Qingyong CHEN ; Guangjun LI ; Yan LI ; Yingjie ZHANG ; Changhu LI ; Long BAI ; Renming ZHONG ; Yinbo HE ; Sen BAI ; Qing YANG ; Feng XU
Chinese Journal of Radiation Oncology 2022;31(3):260-265
Objective:To introduce the stereotactic cardiac radioablation (SCRA) based on the stereotactic body radiotherapy (SBRT), and comprehensively evaluate the new approach by short-term effectiveness and safety.Methods:Patients with ventricular arrhythmia (VA) were evaluated and included in this clinical trial, who were immobilized by vacuum bag and performed simulation with 4-dimensional computed tomography (4DCT). In this study, the planning target volume (PTV) was set as the target to design a SBRT plan using volumetric modulated arc therapy (VMAT), which was evaluated by dose parameters such as R 50%, homogeneity index and conformity index, etc. The results of Holter and echocardiography were monitored during the follow-up and compared with the data before treatment. Results:Three subjects with ventricular tachycardia (VT) and one with premature ventricular contraction (PVC) received the same prescription of 25 Gy in a single fraction. The average volume of PTV was 71.4 cm 3(60.3-89.4 cm 3). The average time of beam delivery was 12.0 min (4.5-21.0 min). And the short-term follow-up lasted for an average of 18 weeks (14-25 weeks), which showed significant decrease in both VT and PVC load without complications. Conclusion:This study reports the implementation method of SCRA and proves its short-term effectiveness and safety, but the effects and standards of the key radiotherapy techniques still need to be explored.
8.Microscopic observation of the enamel microstructures of SD rats with different degrees of fluorosis
Yibo LI ; Feng LI ; Shan GUO ; Li GAO ; Renming GUO ; Liwen LU ; Yanxi ZHANG
Chinese Journal of Stomatology 2021;56(12):1261-1266
Objective:To establish a dental fluorosis model of SD rats with various degrees, to observe the microstructures of enamel samples under scanning electron microscope and to clarify the changes of enamel microstructures with various degrees of dental fluorosis, so as to provide clinical reference for the treatment of patients with moderate and severe dental fluorosis.Methods:Thirty male SD rats (6 weeks of age) were randomly divided into 3 groups with 10 rats in each group. The control group was fed with deionized water without fluoride, the low fluoride group was fed with 50 mg/L NaF deionized water and the high fluoride group was fed with 100 mg/L NaF deionized water in order to establish the dental fluorosis model of rats. After feeding for 6 weeks, the rats were sacrificed and the mandibular incisor teeth were collected and recorded. The surface and sagittal plane of each tooth were observed by scanning electron microscopy and the enamel thickness was measured.Results:In the control group, the enamel color was brown yellow. Enamel color discoloration occurred both in low-fluoride group and high-fluoride group. The enamel color in low-fluoride group was mostly yellow and white striped while in high-fluoride group was mostly chalky white. Under electronic microscope, the enamel rods were alternately arranged and their structure was clear and plump in the control group. The enamel rods of moderate fluorosis were arranged in a straight orientation like tips of bamboo shoots. The enamel rods of severe fluorosis, however, became thinner and the tips of rods were broken. In the control group, sagittal images of enamel turned out to be a dense outer structure with clear boundaries among the inner. The structure of the middle layer was reticulated showing a clear boundary with middle and outer layers. The structure of enamel rods in the inner layers was arranged vertically and horizontally. In the moderate fluorosis group, the outer layer of the enamel became thinner and the middle layer disappeared although the boundary between the outer and middle layers was still clear. In the inner layer, the vertically arranged enamel rods seemed still clear, however the horizontal enamel rods disappeared. In the severe fluorosis group, the outer layer could not be traced. The middle layer was exposed to the air and the inner enamel rods contracted. The inner layers of the enamel had gradually become thinner with the development of the dental fluorosis. The thicknesses of inner layers in control, moderate and the severe groups were (180.71 ±7.01), (157.10 ±11.04) and (121.10 ±12.56) μm respectively. As for the thicknesses of the full layers in the above mentioned three groups, the same trend was observed. The thicknesses, in order of the severity of dental fluorosis, were (241.54 ±7.76), (207.42 ±14.36) and (143.79 ±14.60) μm. Conclusions:With the development of dental fluorosis, the outer enamel layers became thinner or disappeared and the inner enamel layers became thinner or lost its normal structure as well. It is highly recommended that the resin penetration could be used for the proper treatment of moderate and severe dental fluorosis and the strong bleaching and the micro-grinding should be used cautiously.
9.The setup errors of thermoplastic head and shoulder molds with or without vacuum pad in HFSRT for brain metastases in the lung cancer
An LI ; Jia LIU ; Jialu LAI ; Qiang WANG ; Qingfeng XU ; Renming ZHONG ; Yinbo HE ; Sen BAI ; Lin ZHOU
Chinese Journal of Radiation Oncology 2021;30(6):592-597
Objective:To retrospectively analyze the setup errors of thermoplastic head and shoulder molds alone or combined with vacuum pad in hypofractionated stereotactic radiotherapy (HFSRT) for non-small cell lung cancer (NSCLC) with brain metastases.Methods:Fifty-four NSCLC patients with brain metastases who received HFSRT from 2017 to 2019 were enrolled in this study. Twenty-four patients were fixed with thermoplastic head and shoulder molds (group A), and 30 patients were fixed with thermoplastic head and shoulder molds plus vacuum pad (group B). The interfraction and intrafraction setup errors were acquired from cone-beam CT online image registration before and after the HFSRT. Optical surface system was applied in monitoring the intrafraction setup errors. The setup errors in each direction between two groups were analyzed by independent samples t-test. Results:For the interfraction setup errors of the whole group, the proportion of the horizontal setup errors of ≥3mm was 7.0% to 15.4% and 7.0% to 12.6% for the rotation setup errors of ≥2°. In group A, the anteroposterior setup error was (1.035±1.180)mm, significantly less than (1.512±0.955)mm in group B ( P=0.009). In group A, the sagittal rotation setup error was 0.665°±0.582°, significantly less than 0.921°±0.682° in group B ( P=0.021). For the intrafraction setup errors of the whole group, the proportion of horizontal setup errors of ≥1mm was 0% to 0.7%, whereas no rotation setup error of ≥1° were observed. In group B, bilateral, anteroposterior and sagittal rotation setup errors were (0.047±0.212)mm, (0.023±0.152)mm and 0.091°±0.090°, significantly less compared with (0.246±0.474)mm, (0.140±0.350)mm and 0.181°±0.210° in group A ( P=0.004, P=0.020, P=0.001), respectively. Optical surface monitoring data were consistent with the obtained results. Conclusions:Thermoplastic head and shoulder molds (with or without vacuum pad) combined with online image registration and six-dimensional robotic couch correction can be applied in HFSRT for brain metastases from NSCLC. The intrafraction setup errors in group B are smaller than those in group A. Optical surface system has certain value in monitoring the intrafractional movement.
10.Application of Virtual Monochromatic Images Reconstructed by Dual-energy Computed Tomography in Radiotherapy Treatment Planning System.
Jing LI ; Qing XIAO ; Xiangbin ZHANG ; Guyu DAI ; Sen BAI ; Renming ZHONG
Chinese Journal of Medical Instrumentation 2021;45(5):568-572
Virtual monochromatic images (VMI) that reconstructed on dual-energy computed tomography (DECT) have further application prospects in radiotherapy, and there is still a lack of clinical dose verification. In this study, GE Revolution CT scanner was used to perform conventional imaging and gemstone spectral imaging on the simulated head and body phantom. The CT images were imported to radiotherapy treatment planning system (TPS), and the same treatment plans were transplanted to compare the CT value and the dose distribution. The results show that the VMI can be imported into TPS for CT value-relative electron density conversion and dose calculation. Compared to conventional images, the VMI varies from 70 to 140 keV, has little difference in dose distribution of 6 MV photon treatment plan.
Electrons
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Phantoms, Imaging
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Tomography Scanners, X-Ray Computed
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Tomography, X-Ray Computed

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