1.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
Purpose:
The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs).
Materials and Methods:
Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
Results:
A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
Conclusion
USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.
2.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
Purpose:
The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs).
Materials and Methods:
Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
Results:
A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
Conclusion
USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.
3.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
Purpose:
The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs).
Materials and Methods:
Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
Results:
A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
Conclusion
USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.
4.Histopathological changes in secondary visual cortex and enhanced calcium activity in neurons being involved in microwave radiation-induced anxiety-like behavior
Zhihua FENG ; Ting PAN ; Ganghua HE ; Chenxu CHANG ; Zhilin CUI ; Meiying YANG ; Yanhui HAO ; Fengsong LIU ; Yang LI ; Hongyan ZUO
Chinese Journal of Radiological Medicine and Protection 2024;44(6):464-471
Objective:To clarify the effects of microwave radiation on anxiety-like behavior, the histomorphology of the secondary visual cortex, and calcium activity in neurons.Methods:36 C57BL/6N mice were selected and divided into control group and microwave radiation group according to the random number table method. In the simple behavioral testing, there were 8 mice in the control group and 7 mice in the radiation group. Combining fiber optic recording with behavioral experiments, there were 8 mice in the control group and 7 mice in the radiation group. Hematoxylin-eosin (HE) staining was conducted with 3 mice in each group. A high-power microwave simulated source in the X-band with a center frequency of 9.875 GHz and an average power density of 12 mW/cm 2 was used to irradiate the mice for 15 minutes, establishing a microwave radiation animal model. Then, anxiety-like behavior changes in the radiation group were identified using the open-field and elevated plus maze (EPM) tests. The effects of microwave radiation on the histomorphology of the secondary visual cortex were investigated using HE staining and optical microscopy. Based on the genetically encoded calcium imaging technique, as well as optical fiber recording combined with behavioral paradigms in the open field and the EPM, the changes of calcium activity in neurons in the V2M region of the secondary visual cortex were detected. Results:Compared to the control group, the radiation group showed a significant decrease in the frequency of exploring the central region of the open field and the open arm of the EPM ( t = 2.24, 3.10, P < 0.05). Furthermore, the radiation group exhibited the degeneration and apoptosis of some neurons in the secondary visual cortex, primarily manifested as pyknosis and deep staining, cell body shrinkage, and the slightly widening of perivascular space. Fiber optic recordings and behavioral experiments indicated that compared to the control group, mice in the radiation group exhibited significantly increased calcium activities in neurons of the secondary visual cortex when exploring the central region of the open field ( t = -2.75, P < 0.05) or the open arm of the EPM ( t = -2.77, -3.41, P < 0.05) compared to those before radiation after microwave exposure. Conclusions:Microwave radiation can induce anxiety-like behaviors and histopathological changes in the secondary visual cortex. Increased calcium activity in neurons of the secondary visual cortex is proved to be an important mechanism underlying the changes in anxiety-like behavior due to microwave radiation.
5.Mechanism of the therapeutic effect of Tetrandrine on striatum injury caused by microwave radiation
Xiaoxu KONG ; Zhihua FENG ; Xuejia WANG ; Ganghua HE ; Ting PAN ; Zhengtao XU ; Yumeng YE ; Yanhui HAO ; Hongyan ZUO ; Yang LI
Chinese Journal of Radiological Medicine and Protection 2023;43(5):328-334
Objective:To study the therapeutic effect Tetrandrine (TET) on striatal injury caused by microwave radiation and underlying mechanism.Methods:C57BL/6N mice were randomly divided into blank control group (C), radiation control group (R), TET group (TET) and TET combined with radiation group (TET+ R). The mice of radiation group were exposed to 2.856 GHz 8 mW/cm2 microwave on whole-body for 15 min. TET (60 mg/kg) was injected intraperitoneally once a day for 3 consecutive days. The TET structure was verified by ultraviolet spectrophotometry. The open field experiment was used to detect the change of anxiety in mice. Histopathological and ultrastructural changes of the striatum were observed by light microscopy and transmission electron microscopy (TMT). Quantitative real-time PCR (qPCR) was used to detect gene expression changes of voltage-gated calcium channel (VGCC) subtype in the striatum.Results:The open field experiments showed that the time and distance of mice to explore the central region after microwave radiation were significantly lower than that before radiation ( t=4.60, 5.18, P<0.01), and the TET administration significantly improved these changes ( F=1.43, 4.37, P < 0.05). 7 d after microwave radiation, some neuronal nuclei in the striatum of mice contracted and could be stained deeply, which was more obvious in the globus pallidus area. The partial neuronal apoptosis, swelling and cavitation of glial cell mitochondria, blurring of synaptic gaps, and widening of perivascular gaps in the striatum were observed by TMT. The above lesions were significantly rescued after TET administration. But both microwave radiation and TET administration had no significant effect on the gene expressions of striatal VGCC ( P > 0.05). Conclusions:TET has a therapeutic effect on anxiety-like behavior and structural damage of striatum caused by microwave radiation, which is independent of the expression of striatal VGCC genes.
6.Preclinical evaluation and pilot clinical study of 18FAlF-labeled FAPI-tracer for PET imaging of cancer associated fibroblasts.
Kongzhen HU ; Junqi LI ; Lijuan WANG ; Yong HUANG ; Li LI ; Shimin YE ; Yanjiang HAN ; Shun HUANG ; Hubing WU ; Jin SU ; Ganghua TANG
Acta Pharmaceutica Sinica B 2022;12(2):867-875
In recent years, fibroblast activation protein (FAP) has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands. Herein, we aimed to design a novel 18F-labeled FAP tracer ([18F]AlF-P-FAPI) for FAP imaging and evaluated its potential for clinical application. The [18F]AlF-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32 ± 6% (n = 8). Among A549-FAP cells, [18F]AlF-P-FAPI demonstrated specific uptake, rapid internalization, and low cellular efflux. Compared to the patent tracer [18F]FAPI-42, [18F]AlF-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of [18F]AlF-P-FAPI (7.0 ± 1.0% ID/g) compared to patent tracers [18F]FAPI-42 (3.2 ± 0.6% ID/g) and [68Ga]Ga-FAPI-04 (2.7 ± 0.5% ID/g). Furthermore, in an initial diagnostic application in a patient with nasopharyngeal cancer, [18F]AlF-P-FAPI and [18F]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. These results suggest that [18F]AlF-P-FAPI can be conveniently prepared, with promising characteristics in the preclinical evaluation. The feasibility of FAP imaging was demonstrated using PET studies.
7.Effects of viscosity and head position on the surface electromyography of the suprahyoid muscles during swallowing
Lin YUE ; Zhe LI ; Ganghua GUO ; Chenxia GUAN ; Jun GUO ; Daojian HAO ; Zhenzhen LI
Chinese Journal of Physical Medicine and Rehabilitation 2021;43(12):1078-1083
Objective:To explore the effect of swallowing fluids of different viscosities in different head positions on the surface electromyography (sEMG) of the suprahyoid muscles.Methods:Twenty healthy adults were asked to swallow 5ml of liquids with 5 different viscosities in 3 different head positions. sEMG signals were recorded from their suprahyoid muscles in real time. The interactions between viscosity, head position and suprahyoid muscle activation were determined using simple effect analysis.Results:Significant head position and viscosity effects were observed. In the head-turning-right or the right head-flexion position, the net amplitude values of the left suprahyoid muscles were significantly higher than those from the right side when swallowing fluid of the same viscosity. Meanwhile, the net amplitude values of the left suprahyoid muscles increased gradually and significantly from the neutral position to the head-turning-right and the right head-flexion positions. When swallowing fluid with a viscosity of 0 to 3, the net amplitude values of the right suprahyoid muscles in the right head-flexion position were significantly lower than in the neutral and right head-flexion positions. With a viscosity of 4 the values of the former were significantly higher than the latter. The net amplitude of the left superhyoid muscle group when swallowing zero-viscosity food in a head-turning-right position was significantly lower than that when swallowing food of viscosity 1 to 4. In the right head-flexion position, the net amplitude of the left superhyoid muscle group when swallowing zero-viscosity food was significantly lower than that when swallowing food of viscosity 2 to 4. When swallowing fluid of viscosity 1 it was also significantly lower than that when swallowing food of viscosity 3 to 4. In the same position, the net amplitude of the right suprhyoid muscle group when swallowing fluid of viscosity 4 was significantly higher than that with a viscosity of 0 to 1. At viscosity 3 it was significantly higher than with a viscosity of 1.Conclusion:Swallowing fluids of different viscosities in different head positions can affect the contraction of the suprahyoid muscles to different degrees.
8.Effects of magnetic stimulation on astrocyte migration
Chenxia GUAN ; Ganghua GUO ; Yumin ZHAO ; Zhe LI
Chinese Journal of Physical Medicine and Rehabilitation 2018;40(2):81-86
Objective To study the effect of the trauscranial magnetic stimulation on the migration of phosphoprotein-enriched astrocytes-15kDa (PEA-15).Methods Third or fourth generation rat astrocytes cuhured in vitro were divided into a control group,a transfected group,a magnetic stimulation group and a transfected + magnetic stimulation group.The control group was undergone transfect of negative siRNA.In transfected group and the transfected + magnetic stimulation group the liposome in the astrocyte was transfected instantly with chemically synthesized PEA-15 siRNA,so as to interfere with the expression of PEA-15 protein.Magnetic stimulation was applied to both tranfected and transfected + magnetic stimulation groups 24 h after plating of astrocytes at 1 Hz and 60% the maximal output of the stimulator.Cell scratch tests were used to assess the astrocytes' migration,and Western blotting was applied to detect the expression of PEA-15 and protein phosphorylation.Results Compared with the control group,the expression of PEA-15 protein decreased significantly in the transfected groups.The cell migration in the transfected group,the magnetic stimulation group,and the transfected + magnetic stimulation group was significantly greater than in the control group.Compared with the control group,the phosphorylation of PEA-15 increased significantly in the magnetic stimulation group.Conclusion When PEA-15 expression is interfered with,the migration of astrocytes increases significantly.Magnetic stimulation may promote the migration of astrocytes by enhancing PEA-15 phosphorylation.
9.The effects of the inter-stimulus interval in magnetic stimulation on astrocyte migration and its mechanism
Jun GUO ; Zhe LI ; Jiahong FAN ; Ganghua GUO ; Xiaoli LI ; Chenxia GUAN ; Lin YUE
Chinese Journal of Physical Medicine and Rehabilitation 2018;40(5):325-330
Objective To examine the effect of the inter-stimulus interval (ISI) in magnetic stimulation (MS) on astrocyte migration and its related mechanism.Methods Cultured astrocytes were treated with intermittent MS with intervals of 1,5 and 10 seconds.The PEA-15 inhibitor BisI (10 μmol/ml) and the ERK1/2 inhibitor U0126 (10 μmol/ml) were administered and cell migration assays evaluated the astrocytes' migration.The expression of phosphorylated ERK1/2 and PEA-15 was detected using Western blotting.Results The 1 second interval significantly facilitated astrocyte migration,the phosphorylation of PEA-15 and ERK1/2,and the expression of MMP-9 (browse matrix metalloproteinase-9).The addition of Bis I significantly reduced the production of phosphorylated ERK1/2 and MMP-9,as well as astrocyte migration induced by MS.In addition,pretreatment with U0126 also significantly decreased the astrocyte migration induced by MS.Conclusion 1s-ISI MS can induce PEA-15 activation and subsequently lead to ERK1/2 phosphorylation and upregulation of MMP-9,which may contribute to the migration of astrocytes.
10.The characteristics of different skills in the evaluation of postcricoid region and pyriform sinus by fibrolaryngoscope
Gangcai ZHU ; Shisheng LI ; Ou PENG ; Shaohong LI ; Ganghua ZHU ; Shuhui WANG ; Xiangbo HE ; Qinglai TANG ; Xinming YANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2018;53(4):298-301

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