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.Analysis of the pre-metabolic disease state based on the theory of "overflow of Wu Qi"
Qing HE ; Zirong LI ; Qiaoli YANG ; Jing LIN ; Guangqi WANG ; Jin QIN ; Shangjian LIU
International Journal of Traditional Chinese Medicine 2024;46(3):278-282
The pre-metabolic disease state is the body state of substance metabolism disorder that has not yet reached the physical and chemical indicators of the disease, and abnormal glucose metabolism is often the key link of metabolic disorder. In TCM, the healthy function of the spleen is the cornerstone of the production and distribution of fine substances. This article discussed the pre-metabolic disease state based on the theory of "overflow of Five Qi" in the Nei Jing, taking the loss of spleen preparedness as the starting point, in order to provide new ideas and directions for the prevention and treatment of clinical metabolic diseases.
5.Targets and validation of Salvia miltiorrhiza in myopia through network pharmacology
Xiaonan LU ; Jie LI ; Guangqi AN ; Zhenhui LIU ; Chunyu LIANG ; Shuzhen DAI
Chinese Journal of Experimental Ophthalmology 2024;42(4):322-328
Objective:To explore and validate the targets of Salvia miltiorrhiza in myopia using network pharmacology and molecular docking technology. Methods:The TCMSP database was used to extract the targets of Salvia miltiorrhiza.GeneCards, DisGeNET, Malacard and OMIM databases were used to extract the myopia-related targets.The target intersection was taken, and the intersecting targets were selected to extract the corresponding active ingredients of traditional Chinese medicine (TCM) and construct the pharmacological regulatory network of TCM using Cytoscape.The protein interaction network map for the key target genes was constructed using the String database, and the relevant proteins were selected to download the three-dimensional structures of the active ingredients from the PubChem database, and molecular docking was performed using AutoDockvina software.Twelve 3-week-old guinea pigs were induced with lens-induced myopia (LIM) in the right eye and randomly divided into normal saline group and sodium danshensu group, with 6 animals in each group.During the maintenance of LIM, periocular injection of 1 ml normal saline or sodium danshensu was performed daily.The contralateral eye was used as a negative control.On days 0, 14, and 28 of the experiment, the axial length of both eyes was measured by A-scan ultrasonography, and the refractive status was assessed with a streak retinoscope.To avoid individual differences, relative spherical equivalent (treated eye-contralateral eye) and relative axial length (treated eye-contralateral eye) were compared.On day 28, the relative expression levels of hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1) proteins were determined by Western blot.The feeding and use of laboratory animals followed the 3R principle, and the research program was approved by the Ethics Committee of Experimental Animal Center of Zhengzhou University (No.ZZU-LAC 202320405[02]). Results:Sixteen intersecting key targets were screened for myopia and TCM components derived from Salvia divinorum.A TCM network pharmacology map and protein interaction map were constructed with Salvia divinorum as a drug candidate, and the corresponding proteins of target genes, such as MMP2, TGFB1, and MMP9 were screened to perform molecular docking with the active ingredients, such as lignocellulosic acid, danshensu, tanshinone ⅡA, and so on.After 14 days of induction, the relative spherical equivalent and relative axial length were (-4.67±1.03)D and (0.67±0.26)mm in sodium danshensu group, and (-6.30±1.22)D and (1.08±0.34)mm normal saline group, indicating slower myopia progression and axial elongation in sodium danshensu group, and the differences were statistically significant ( t=2.412, P=0.039; t=2.750, P=0.049). The relative expression levels of HIF-1α protein were 0.20±0.01, 1.29±0.05 and 0.63±0.02, and the relative expression levels of TGF-β1 protein were 0.93±0.05, 0.25±0.01 and 0.74±0.05 in the negative control, normal saline and sodium danshensu groups, respectively.The expression of HIF-1α protein was higher in sodium danshensu group than in negative control group but lower than in the normal saline group, and the expression of TGF-β1 protein was lower in sodium danshensu group than in negative control group but higher than in the normal saline group, showing statistically significant differences (all at P<0.05). Conclusions:Natural compounds extracted from Salvia divinorum extracts may serve as potential drug candidates to combat scleral hypoxia and improve scleral extracellular matrix remodeling.
6.Establishment of a rat model with aortic dissection induced by β-aminopropionitrile combined with angiotensin Ⅱ
Yi ZHANG ; Xinmei LIU ; Guangqi ZHOU ; Yanli QIAO ; Haiyang HU ; Hongsheng LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):127-134
Objective To investigate the optimal administration combination of β-aminopropionitrile (BAPN) and Angiotensin Ⅱ (Ang-Ⅱ) in the establishment of SD rat aortic dissection (AD) model and the related complications. Methods Forty-two three-week-old male SD rats were randomly divided into 7 groups: a group A (0.25% BAPN), a group B (0.40% BAPN), a group C (0.80% BAPN), a group D [1 g/(kg·d) BAPN], a group E [1 g/(kg·d) BAPN+ 1 μg/(kg·min) saline], a group F [1 g/(kg·d) BAPN+1 μg/(kg·min) Ang-Ⅱ] and a group G (control group). There were 6 rats in each group. The intervention period was 4 weeks (groups E and F were 4 weeks+5 days). Rats were dissected immediately if they died during the experiment. After the intervention, the surviving rats were sacrificed by pentobarbital sodium, and the whole aorta was separated and retained. Hematoxylin-eosin staining was used to observe the changes of aorta from the pathological morphology. Results There was no statistical difference in the survival rate among the groups after 4 weeks of BAPN intervention (P>0.05). After 5 days of mini-osmotic pumps implantation, the survival rate of rats was higher in the group E than that in the group F (P=0.008), and the incidence of AD in the group E was lower than that in the group F (P=0.001). BAPN could affect the food and water intake of rats. After BAPN intervention for 4 weeks, the body weight of rats in the group G was higher than those in the intervention groups (P<0.05). BAPN combined with Ang-Ⅱ could make the aortic intima thick, elastic fiber breakage, arrangement disorder, and inflammatory cell infiltration in rats, which conformed to the pathological and morphological changes of AD. BAPN could also affect mental state and gastrointestinal tract. Conclusion The combination of BAPN [1 g/(kg·d)] and Ang-Ⅱ [1 μg/(kg·min)] can stably establish AD model in rats, which will provide a stable carrier for further study of the pathogenesis and therapeutic targets of AD. However, the complications in this process are an unstable factor. How to balance the influence of BAPN on other tissues and organs in the process of AD model establishment remains to be further studied.
7.Clinicopathologic and molecular genetic featuresof metastatic follicular thyroid carcinoma:analyses of 22 cases
Wenwen RAN ; Yixuan LIU ; Weimao KONG ; Qianqian QIAO ; Guangqi LI ; Jigang WANG
Chinese Journal of Clinical and Experimental Pathology 2023;39(12):1453-1459
ABSTARCT Purpose To investigate the clinicopathologic characteristics and genetic mutations of metastatic follicular thy-roid carcinoma(FTC).Methods A total of 22 cases of meta-static FTC were collected,including previous medical history,imaging,treatments and outcomes,and next-generation sequen-cing study and Sanger sequencing were performed in 12 cases.Results There were 16 women and 6 men.Sixteen cases were older than 50 years.Seven cases presented with metastases as the first symptom.Fourteen cases developed metastases 3 to 12 years after thyroid surgery.Sixteen cases developed bone metas-tasis,10 cases had lung metastasis,and 3 cases had brain me-tastasis.Those patients with multiple bone metastases progressed during the follow-up period.The common gene mutations in me-tastases were NRAS p.Q61R(6 cases),HRAS p.Q61R(2 ca-ses)and KRAS p.Q61R(1 case),followed by TERT promoter mutation(8 cases).Other mutated genes included KEL,BRCA1/2,ALK,ROS1,ErbB4,etc.Conclusion FTC has a high misdiagnosis rate.Those diagnosed with FTC should under-go regular systemic examinations to detect potential metastasis,especially in bone,lung,and brain.Further research on the sig-nificance of NRAS and other molecular indicators in FTC metas-tasis will help to better predict its biological behaviors.
8.Changes of choroidal biomarkers in patients with central serous chorioretinopathy
Pei LIU ; Guangqi AN ; Chenyu LU ; Shu LI ; Liping DU ; Xuemin JIN
Chinese Journal of Ocular Fundus Diseases 2023;39(4):290-296
Objective:To quantitatively evaluate the changes of choroidal biomarkers in patients with central serous chorioretinopathy (CSC) and preliminarily explore its pathogenesis.Methods:Clinical cross-sectional study. From July 2021 to December 2022, 74 eyes of 65 patients with CSC (CSC group) confirmed by ophthalmic examination at the First Affiliated Hospital of Zhengzhou University were included in the study. Among them, 46 patients (51 eyes) were male, 19 patients (23 eyes) were female. The duration from the onset of symptoms to the time of treatment was less than or equal to 3 months. A control group consisted of 40 healthy volunteers (74 eyes) matched in age and gender. Among them, 26 patients (50 eyes) were male, and 14 patients (24 eyes) were female. Using VG200D from Microimaging (Henan) Technology Co., Ltd., macular scanning source light coherence tomography angiography was performed, with scanning range 6 mm × 6 mm. According to the division of the diabetes retinopathy treatment research group, the choroid within 6 mm of the macular fovea was divided into three concentric circles centered on the macular fovea, namely, the central area with a diameter of 1 mm, the macular area with a diameter of 1-3 mm, and the surrounding area of the fovea with a diameter of 3-6 mm. The device comes with software to record the three-dimensional choroidal vascular index (CVI), choroidal vascular volume (CVV), perfusion area of the choroidal capillary layer (CFA), choroidal thickness (CT), and three-dimensional CVI, CVV, and CT in the upper, temporal, lower, and subnasal quadrants within 6 mm of the fovea. Quantitative data between the two groups were compared using an independent sample t-test. Qualitative data comparison line χ2 inspection. The value of receiver operating curve (ROC) analysis in predicting the occurrence of CSC, including CVI, CVV, CFA, and CT. Results:Compared with the control group, the CVI ( t=3.133, 4.814), CVV ( t=7.504, 9.248), and CT ( t=10.557, 10.760) in the central and macular regions of the affected eyes in the CSC group significantly increased, while the CFA ( t=-8.206, -5.065) significantly decreased, with statistically significant differences ( P<0.05); CVI ( t=7.129), CVV ( t=10.020), and CT ( t=10.488) significantly increased within 6 mm of the central fovea, while CFA ( t=-2.548) significantly decreased, with statistically significant differences ( P<0.05). The CVI ( t=4.980, 4.201, 4.716, 8.491), CVV ( t=9.014, 7.156, 7.719, 10.730), and CT ( t=10.077, 8.700, 8.960, 11.704) in the upper, temporal, lower, and lower nasal quadrants within 6 mm of the central fovea were significantly increased, with statistically significant differences ( P<0.05). In the CSC group, the maximum CVI and CVV were (0.39±0.10)% and (1.09±0.42) mm 3, respectively, on the nasal side of the affected eye. Upper CT was (476.02±100.89) μm. The nasal side CVI, CVV, and CT have the largest changes. The ROC curve analysis results showed that the area under the curve of CT, CVV, and CVI within 6 mm of the central region, macular region, and fovea was over than 0.5. Subcentral CT was the most specific for the diagnosis of CSC. Conclusion:Choroidal biomarkers CVI, CVV, and CT in CSC patients increase, while CFA decreases. Central CT is the most specific for the diagnosis of CSC.
9.Observation of vortex venous anastomosis in central serous chorioretinopathy
Pei LIU ; Guangqi AN ; Min ZHANG ; Haixin FANG ; Fan YANG ; Liping DU ; Xuemin JIN
Chinese Journal of Ocular Fundus Diseases 2023;39(4):307-311
Objective:To observe the anastomotic status of the vortex veins in patients with central serous chorioretinopathy (CSC).Methods:A cross-sectional study of clinical practice. From July 2021 to July 2022, 50 cases (50 eyes) of monocular CSC patients diagnosed through ophthalmic examination at the First Affiliated Hospital of Zhengzhou University were included in the study. Among them, there were 37 males (74.0%, 37/50) and 13 females (26.0%, 13/50), with the mean age of (44.30±9.59) years old. The course of disease from the onset of symptoms to the time of treatment was less than 3 months. The affected eye and contralateral eye of CSC patients were divided into the affected eye group and contralateral eye group, respectively. Fifty healthy volunteers of the same age and gender were selected as the normal control group with 50 eyes. The macular area scanning source optical coherence tomography (OCT) vascular imaging examination was performed with Visual Microimaging (Henan) Technology Co., Ltd. VG200D. Horizontal watershed vortex veins anastomosis rate and asymmetric vortex-venous dilation rate were observed by en face OCT. The device comes with software to calculate the central foveal choroidal thickness (SFCT), mean choroidal thickness (MCT), and choroidal vascular index (CVI). One-way analysis of variance and χ2 test were used to compare the three groups. When variances were unequal between groups, nonparametric tests were performed. Results:The SFCT values of the affected eye group, contralateral eye group, and normal control group were (567.12±129.02), (513.26±133.17), (327.64±97.40) μm, respectively; MCT were (407.38±97.54), (388.24±94.13), (275.46±60.55) μm, respectively; CVI were 0.34±0.05, 0.32±0.04, and 0.27±0.04, respectively; anastomosis rates of vortex veins were 98% (49/50), 78% (39/50), and 40% (20/50), respectively; asymmetric dilation rates of vortex veins were 96% (48/50), 88% (44/50), and 48% (24/50), respectively. The differences of SFCT ( F=53.974), MCT ( Z=51.415), CVI ( F=28.082), vortex vein anastomosis rate ( χ2=43.056), asymmetric dilation rate of vortex veins ( χ2=37.728) among three groups were statistically significant ( P<0.001). Compared with the contralateral eye group, the SFCT, MCT, CVI, vortex vein anastomosis rate, and vortex vein asymmetric dilation rate in the affected eye group were significantly higher than those in the contralateral eye group. Among them, the differences of SFCT ( t=2.054), CVI ( t=2.211), and vortex vein anastomosis rate ( χ2=9.470) were statistically significant ( P<0.05); the differences of MCT ( Z=7.490), asymmetric dilation rate of vortex veins ( χ2=2.714) were not statistically significant ( P=1.000, 0.140). Conclusions:SFCT, MCT, and CVI in the affected and contralateral eyes of monocular CSC patients significantly increase. The anastomotic rate and asymmetric dilation rate of the vortex vein in the opposite eye were lower than those in the affected eye.
10.Public health preparedness and responses to the coronavirus disease 2019 (COVID-19) pandemic in South Asia: a situation and policy analysis
Sarkar AMITABHA ; Guangqi LIU ; Yinzi JIN ; Xie ZHENG ; Zhi-Jie ZHENG
Global Health Journal 2020;4(4):121-132
Like rest of the world, the South Asian region is facing enormous challenges with the coronavirus disease 2019 (COVID-19) pandemic. The socio-economic context of the eight South Asian countries is averse to any long-term lockdown program, but the region still observed stringent lockdown close to two months. This paper analyzed major measures in public health preparedness and responses in those countries in the pandemic. The research was based on a situation analysis to discuss appropriate plan for epidemic preparedness, strategies for prevention and control measures, and adequate response management mechanism. Based on the data from March 21 to June 26, 2020, it appeared lockdown program along with other control measures were not as effective to arrest the exponential growth of fortnightly COVID-19 cases in Afghanistan, Bangladesh, India, Nepal and Pakistan. However, Bhutan, Maldives and Sri Lanka have been successfully limiting the spread of the disease. The in-depth analysis of prevention and control measures espoused densely populated context of South Asia needs community-led intervention strategy, such as case containment, in order to reverse the growing trend, and adopt the policy of mitigation instead of suppression to formulate COVID-19 action plan. On the other hand, mechanism for response management encompassed a four-tier approach of governance to weave community-led local bodies with state, national and international governance actors for enhancing the countries' emergency operation system. It is concluded resource-crunch countries in South Asia are unable to cope with the disproportionate demand of capital and skilled health care workforce at the time of the pandemic. Hence, response management needs an approach of governance maximization instead of resource maximization. The epidemiologic management of population coupled with suitable public health prevention and control measures may be a more appropriate strategy to strike a balance between economy and population health during the time of pandemic.

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