1.BnaNRT1.5s mediates nitrate transporter to regulate nitrogen use efficiency in Brassica napus.
Shilong CHEN ; Lei YAO ; Rumeng WANG ; Jian ZENG ; Jianghe LI ; Shiyao CUI ; Xu WANG ; Haixing SONG ; Zhenhua ZHANG ; Pan GONG
Chinese Journal of Biotechnology 2025;41(7):2954-2965
Improving the nitrogen use efficiency (NUE) of Brassica napus is of significant importance for achieving the national goal of zero growth in chemical fertilizer application and ensuring the green development of the rapeseed industry. This study aims to explore the effects of the nitrate transporter gene BnaNRT1.5s on the nitrogen transport and NUE of B. napus, providing excellent genetic resources for the development of nitrogen-efficient B. napus varieties. The spatiotemporal expression of BnaA05.NRT1.5 as a key nitrogen responsive gene was profiled by qRT-PCR at different growth stages and for different tissue samples of B. napus 'Westar'. Subcellular localization was employed to examine its expression pattern in the cells. Additionally, CRISPR/Cas9 was used to create BnaNRT1.5s knockout lines, which were subjected to hydroponic experiments under high nitrogen (12.0 mmol/L) and low nitrogen (0.3 mmol/L) conditions. After the seedlings were cultivated for 21 days, root and shoot samples were collected for weighing, nitrogen content determination, xylem sap nitrate content assessment, and calculation of total nitrogen and NUE. The B. napus nitrate transporter BnaA05.NRT1.5 was localized to the cell membrane. During the seedling and early bolting stages, BnaA05.NRT1.5 was predominantly expressed in roots, while it was highly expressed in old leaves and mature silique skin during the reproductive stage. Compared with the wild type, the mutant BnaNRT1.5s showed significant increases in the dry weight and total nitrogen of seedlings under both high and low nitrogen conditions. Under low nitrogen conditions, NUE in the roots of BnaNRT1.5s significantly improved. Notably, under both high and low nitrogen conditions, the nitrate content in the shoots of BnaNRT1.5s decreased significantly, while that in the roots increased significantly, resulting in a significantly decreased shoot-to-root nitrate content ratio. BnaNRT1.5s is involved in regulating the transport of nitrate from the roots to the shoots, and its mutation enhances nitrogen absorption and utilization in B. napus seedlings, promoting seedling growth. This study not only provides references for understanding the physiological and molecular mechanisms by which BnaNRT1.5s regulates NUE but also offers valuable genetic resources for improving NUE in B. napus.
Brassica napus/genetics*
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Anion Transport Proteins/metabolism*
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Nitrogen/metabolism*
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Nitrate Transporters
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Plant Proteins/metabolism*
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Nitrates/metabolism*
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Gene Expression Regulation, Plant
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Biological Transport
2.Effect of Jiawei Ditan Decoction on neurological function,PTX-3 and VEGF in patients with post-ischemic stroke cognitive impairment
Yuyu LIU ; Rumeng ZHANG ; He ZHU ; Lailai WEI ; Linfei LI ; Qian HU ; Xiujuan WANG
Journal of Navy Medicine 2025;46(9):923-927
Objective To investigate the effects of Jiawei Ditan Decoction on neurological function,pentraxin-3(PTX-3),and vascular endothelial growth factor(VEGF)in patients with post-ischemic stroke cognitive impairment(PSCI).Methods A total of 97 patients with PSCI who were admitted to Xuzhou Central Hospital from March 2022 to March 2024 were enrolled and randomly assigned to control group(n=48)or decoction group(n=49)using the envelope drawing method.The control group received conventional treatment,while the decoction group was additionally treated with Jiawei Ditan Decoction.Clinical efficacy,Traditional Chinese Medicine(TCM)syndrome scores,cognitive and functional assessments,laboratory markers,and oxidative stress levels were compared between the two groups.Results The total effective rate in the decoction group was significantly higher than that in the control group(P<0.05).At 3 and 6 months after treatment,TCM syndrome scores in the decoction group were lower than those in the control group(P<0.05).The scores of the Montreal cognitive assessment(MoCA),mini-mental state examination(MMSE),and Barthel index(BI)in the decoction group were higher than those in the control group at 3 months after treatment,while the National Institutes of Health stroke scale(NIHSS)score in the decoction group was lower than that in the control group(P<0.05).At 1 month after treatment,PTX-3 and hypersensitive C-reactive protein(hs-CRP)levels in the decoction group were lower than those in the control group,while VEGF,superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and nitric oxide(NO)levels in the decoction group were higher than those in the control group(P<0.05).Conclusion Jiawei Ditan Decoction exhibits significant effects on improving neurological function and modulating PTX-3 and VEGF levels in patients with PSCI.
3.The influence of enriched environment on cognitive impairment and GAP-43 content changes in pregnant mice with obstructive sleep apnea-hypopnea syndrome through regulating the NF-κB/NLRP3 pathway
Yunzhou Cheng ; Xueyan Li ; Yueming Zhang ; Rumeng Wei ; Yang Wang
Acta Universitatis Medicinalis Anhui 2025;60(7):1212-1217
Objective :
To investigate the effect of environmental enrichment on cognitive impairment and hippo- campus GAP-43 changes induced by exposure to obstructive sleep apnea-hypopnea syndrome ( OSAHS) during the period of late pregnancy in mice,and to explore relative inflammatory pathway mechanism.
Methods :
The experi- mental group of C57BL/6J pregnant mice were exposed to an intermittent hypoxic environment for 7 consecutive days starting from gestational day 15.The corresponding offspring were then placed in an enriched environment from postnatal day 21 to 2 months of age (designated as OSAHS + EE group) or in a normal environment (designat- ed as OSAHS group) .Pregnant mice in the control group were maintained in a normal oxygen environment,and their corresponding offspring were placed in an enriched environment (designated as Control + EE group) or a nor- mal environment (designated as Control group) at the same ages.The spatial learning and memory ability of the mice was assessed by Morris water maze at the age of 2 months.The mRNA levels of NF-kB,NLRP3 and GAP-43 in the hippocampus were detected by real-time fluorescence quantitative PCR , and the protein levels of NLRP3 and GAP-43 in the hippocampus were detected by Western blot.
Results:
Compared with Control group,the swimming distance increased (P<0. 01) ,and the percentage of swimming distance in target quadrant decreased (P<0. 01) in OSAHS group.The level of NF - κB mRNA,NLRP3 mRNA and protein in the hippocampus was increased,and the level of GAP-43 mRNA and protein was decreased (P<0. 01) .Compared with the Control group,there were no significant differences in swimming distance,percentage of swimming distance,NF-κB mRNA,NLRP3 mRNA and protein content in the OSAHS + EE group.
Conclusion
OSAHS during pregnancy impairs the learning and memory ability of offspring mice and reduces the level of GAP-43 protein.The mechanism may be related to the in- crease of NF-κB / NLRP3 level,and environmental enrichment can improve the damage.
4.Exploration on the Formation,Evolution,and Alienation of Syndrome Differentiation and Treatment
Sicheng WANG ; Linhua ZHAO ; Rumeng TANG ; Lili ZHANG
Journal of Traditional Chinese Medicine 2025;66(12):1202-1206
Syndrome differentiation and treatment is an integral part of the traditional Chinese medicine (TCM) diagnostic and therapeutic system, whose development exhibits distinct stages. This paper systematically reviews the evolutionary trajectory of syndrome differentiation and treatment, from symptom-based treatment in Inner Canon of Yellow Emperor (《黄帝内经》), to ZHANG Zhongjing's establishment of the disease-pulse-syndrome-treatment framework, through its application and development in the Ming and Qing dynasties, and finally to its recognition as a fundamental characteristic of TCM in modern times. However, the overemphasis on syndrome differentiation and treatment, coupled with a diminished focus on disease concepts, has led to its gradual alienation as the primary diagnostic and therapeutic model. The alienation mainly manifests as a tendency to prioritize syndrome over disease, resulting in the overgeneralization and limited application of the concept, and causing a lack of specificity in practice. This paper emphasizes that a correct understanding of syndrome differentiation and treatment is a necessary premise for the deve-lopment and improvement of the TCM diagnostic and therapeutic system. By integrating modern medical diagnosis to clarify disease targets and applying TCM thinking to extract common patterns of diseases, precise alignment between syndrome differentiation and treatment and modern clinical demands can be achieved, providing a reference for addressing the contemporary challenges of syndrome differentiation and treatment.
5.Establishment of nuclear grade prediction model for T1 clear cell renal cell carcinoma based on CT features and radiomics
Caiyong ZHAO ; Chao CHEN ; Weiwei LI ; Jie WANG ; Rumeng ZHENG ; Feng CUI
Chinese Journal of Oncology 2025;47(2):168-174
Objective:To investigate the clinical value of the prediction models constructed by CT based imaging features and radiomics for World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading in pre-operative patients with T1 clear cell renal cell carcinoma (ccRCC).Methods:Ninety patients with ccRCC diagnosed at Hangzhou Hospital of Traditional Chinese Medicine from January 2016 to December 2023 were enrolled as the training set, and 43 patients diagnosed at the Sir Run Run Shaw Hospital from January 2017 to December 2018 were enrolled as the external validation set. According to the WHO/ISUP grading system, grades Ⅰ and Ⅱ were defined as the low grade group, and grades Ⅲ and Ⅳ were defined as the high grade group. In the training set, 64 patients were in the low grade group and 26 patients in the high grade group. In the external validation set, 33 patients were in the low grade group and 10 patients in the high grade group. The multivariate logistic regression was used to establish an imaging factor model based on CT imaging features in the training set. The 3-dimensional regions of interest were manually contoured at the cortical phase of enhanced CT, and the radiomics features were extracted. Linear correlation between features and L1 regularization were used for feature selection, and then linear support vector classification was used to construct the radiomics model. After that, a combined diagnostic model of nomogram combining the radiomics score and imaging factors was constructed using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of each model. The Delong test was used for comparison of the areas under the ROC curve.Results:The imaging factor model, the radiomics model, and the combined diagnostic model of nomogram were successfully constructed to predict the WHO/ ISUP grading in stage T1 ccRCC. The AUC value of the imaging factor model in the training and validation sets was 0.742 (95% CI: 0.623-0.860) and 0.664 (95% CI: 0.448-0.879), respectively. The AUC values of the radiomics model in the two sets were 0.914 (95% CI: 0.844-0.983) and 0.879 (95% CI: 0.718-1.000), and of the combined diagnostic model of nomogram in the two sets were 0.929 (95% CI: 0.858-0.999) and 0.882 (95% CI: 0.710-1.000), respectively. The AUCs of the radiomics model and combined diagnostic model of nomogram were significantly higher than that of the imaging factor model (both P<0.05). There was no statistical difference in the AUCs between the combined diagnostic model of nomogram and the radiomics model (both P>0.05). Conclusion:The CT-based radiomics model and combined diagnostic model of nomogram incorporating radiomics signature and imaging features showed favorable predictive efficacy for the preoperative prediction of WHO/ISUP grading in stage T1 ccRCC.
6.The Effect of MAGE-A3 Gene on the Biological Behavior and Drug Resistance of Ovarian Cancer
Rumeng WANG ; Ning ZHANG ; Yanan JI
Journal of Practical Obstetrics and Gynecology 2025;41(2):150-157
Objective:To investigate the effects of knockdown and overexpression of melanoma-associated antigen-A3(MAGE-A3)gene on the biological behavior and cisplatin resistance of ovarian cancer cells.Methods:The expression level of MAGE-A3 mRNA and protein in ovarian cancer cells was detected.The knockdown cell lines were constructed and divided into control group,no-load(NC)group and sh MAGE-A3 group.The overex-pression cell lines were divided into control group,no-load(NC)group and OE-MAGE-A3 group.The effects of knockdown and overexpression of MAGE-A3 gene on the proliferation,migration,invasion and apoptosis of tumor cells were compared.The expression of p53,Survivin,breast cancer susceptibility gene 1(BRCA1)and MAGE-A3 protein was detected.The high expression cell lines were divided into control group,cisplatin group,shMAGE-A3 group and cisplatin+shMAGE-A3 group.The low expression cell lines were divided into control group,cisplatin group,OE-MAGE-A3 group and cisplatin+OE-MAGE-A3 group.The cell proliferation,invasion ability of each group of cells,as well as their effects on the mRNA and protein expression level of each gene were compared.Results:The mRNA and protein expression of MAGE-A3 was high in SKOV3 cells and low in A2780 cells.Com-pared with the control group and NC group,the shMAGE-A3 group had lower OD450 value,migration rate and in-vasion numbers,higher apoptosis rate,lower expression of MAGE-A3 and Survivin protein,and higher expression of BRCA1 and p53 protein.The results of OE-MAGE-A3 group compared with control group and NC group were opposite to those of shMAGE-A3 group.Compared with the control group,cisplatin group and sh-MAGE-A3 group,the cisplatin+sh-MAGE-A3 group had lower OD450 value and invasion number higher levels of p53 and BRCA1 mRNA and protein expression,and lower levels of Survivin mRNA and protein.The OD450 value and in-vasion number of cells in cisplatin+OE-MAGE-A3 group were higher than those in cisplatin group,but lower than those in control group and OE-MAGE-A3 group.The mRNA and protein expression levels of p53 and BRCA1 were higher than those in the control group and the OE-MAGE-A3 group,but lower than those in the cisplatin group.The expression levels of Survivin mRNA and protein were lower than those in the control group and the OE-MAGE-A3 group,and higher than those in the cisplatin group.Conclusions:Knockdown of MAGE-A3 expression can effectively inhibit the proliferation,migration and invasion of ovarian cancer cells,promote apoptosis and en-hance cisplatin sensitivity.On the contrary,overexpression of MAGE-A3 increases cell proliferation,migration and invasion,and reduced apoptosis,thereby conferring cisplatin resistance.
7.Inhibitory effect of SIS3 on trabecular meshwork fibrosis in mice with glucocorticoid-induced ocular hypertension and its mechanism
Jing REN ; Shichao DUAN ; Huiling CUI ; Di WANG ; Rumeng ZHAO ; Qian LIU ; Haijun LI
Chinese Journal of Experimental Ophthalmology 2025;43(5):403-410
Objective:To explore the effect of specific inhibitor of Smad3 (SIS3) on glucocorticoid-induced ocular hypertension in mice and its possible mechanism.Methods:Fifty-one eight-week-old female C57BL/6J mice were randomly divided into control group, dexamethasone group and SIS3 group by the random number table method, with 17 mice in each group.Mice in the control group were injected with 20 μl 2 % polyvinyl alcohol into the conjunctival fornix every week for 4 weeks.Mice in the dexamethasone group and SIS3 group were injected with 20 μl 10 mg/ml dexamethasone acetate every week and SIS3 group was treated with additional 100 μg/ml SIS3 nanomicelle eye drops 3 times daily for up to 4 weeks.Intraocular pressure (IOP) was measured weekly using Icare rebound tonometer.Mice were sacrificed 4 weeks after treatment, and the eyeballs were removed.Morphology of trabecular meshwork (TM) tissues were detected by hematoxylin-eosin (HE) staining.The collagen deposition area in TM tissues were examined by Masson staining.Fibronectin (FN) and collagen type Ⅰ (Col-1) in the extracellular matrix of TM tissue were detected by immunofluorescence staining.TM tissues were obtained from donated patients, and primary human trabecular meshwork cells (HTMCs) were obtained by culture.The expression level of myocilin in dexamethasone-induced HTMCs was detected by immunofluorescence and Western blot for cell identification.Primary HTMCs were divided into normal control group, dexamethasone group and SIS3 group cultured with normal culture medium, medium containing 400 nmol/L dexamethasone, medium containing 400 nmol/L dexamethasone+ 10 μmol/L SIS3 for 48 hours, respectively.The expression levels of FN, Col-1 and p-Smad3/Smad3 proteins were measured by Western blot.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Animal Ethics Committee of Zhengzhou University (No.ZZU-LA20220729).The collection of TM tissue specimens complied with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Henan Provincial Eye Hospital (No.HNEECKY-2022[18]).The patients knew the purpose of the experiment and signed the informed consent forms.Results:There was a significant overall difference in IOP among the three groups at different time points after administration ( Fgroup=72.94, P<0.001; Ftime=33.19, P<0.001).Compared with baseline, IOP was increased in the dexamethasone group at each time point after administration, and the differences were statistically significant (all P<0.001).The IOP of the control and SIS3 groups at weeks 1, 2, 3, 4 were significantly lower than that of the dexamethasone group (all P<0.001).HE staining showed that the iridocorneal angles of all groups were open with similar morphology of the TM structure.Masson staining showed that the positive expression area of collagen in the control group, dexamethasone group and SIS3 group was (9.57±2.91)%, (27.75±5.88)% and (11.67±3.78)%, respectively, with a statistically significant difference among the three groups ( F=25.91, P<0.001), and the positive expression area of collagen was significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.001).The fluorescence expression level of FN in the control group, dexamethasone group and SIS3 group was 8.00±1.92, 14.01±2.74 and 7.85±0.64, respectively, and the fluorescence expression level of Col-1 was 6.90±1.16, 14.36±3.19 and 4.90±0.88, respectively, with statistically significant differences among the three groups ( F=15.93, 30.29; both P<0.001), and the fluorescence expression levels of FN and Col-1 were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.01).Immunofluorescence staining and Western blot showed that the cultured primary cells expressed myocilin and the expression level of myocilin was significantly increased after dexamethasone induction, which was identified as HTMCs.There were statistically significant differences in the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins among different groups of cells ( F=8.22, 23.08, 8.78; all P<0.05), and the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.05). Conclusions:SIS3 reduces IOP by inhibiting p-Smad3, reducing extracellular matrix deposition in TM, and reducing fibrosis in the TM tissue.
8.Inhibitory effect of SIS3 on trabecular meshwork fibrosis in mice with glucocorticoid-induced ocular hypertension and its mechanism
Jing REN ; Shichao DUAN ; Huiling CUI ; Di WANG ; Rumeng ZHAO ; Qian LIU ; Haijun LI
Chinese Journal of Experimental Ophthalmology 2025;43(5):403-410
Objective:To explore the effect of specific inhibitor of Smad3 (SIS3) on glucocorticoid-induced ocular hypertension in mice and its possible mechanism.Methods:Fifty-one eight-week-old female C57BL/6J mice were randomly divided into control group, dexamethasone group and SIS3 group by the random number table method, with 17 mice in each group.Mice in the control group were injected with 20 μl 2 % polyvinyl alcohol into the conjunctival fornix every week for 4 weeks.Mice in the dexamethasone group and SIS3 group were injected with 20 μl 10 mg/ml dexamethasone acetate every week and SIS3 group was treated with additional 100 μg/ml SIS3 nanomicelle eye drops 3 times daily for up to 4 weeks.Intraocular pressure (IOP) was measured weekly using Icare rebound tonometer.Mice were sacrificed 4 weeks after treatment, and the eyeballs were removed.Morphology of trabecular meshwork (TM) tissues were detected by hematoxylin-eosin (HE) staining.The collagen deposition area in TM tissues were examined by Masson staining.Fibronectin (FN) and collagen type Ⅰ (Col-1) in the extracellular matrix of TM tissue were detected by immunofluorescence staining.TM tissues were obtained from donated patients, and primary human trabecular meshwork cells (HTMCs) were obtained by culture.The expression level of myocilin in dexamethasone-induced HTMCs was detected by immunofluorescence and Western blot for cell identification.Primary HTMCs were divided into normal control group, dexamethasone group and SIS3 group cultured with normal culture medium, medium containing 400 nmol/L dexamethasone, medium containing 400 nmol/L dexamethasone+ 10 μmol/L SIS3 for 48 hours, respectively.The expression levels of FN, Col-1 and p-Smad3/Smad3 proteins were measured by Western blot.The use and care of animals complied with the ARVO statement.This study protocol was approved by the Animal Ethics Committee of Zhengzhou University (No.ZZU-LA20220729).The collection of TM tissue specimens complied with the Declaration of Helsinki and was approved by the Medical Ethics Committee of Henan Provincial Eye Hospital (No.HNEECKY-2022[18]).The patients knew the purpose of the experiment and signed the informed consent forms.Results:There was a significant overall difference in IOP among the three groups at different time points after administration ( Fgroup=72.94, P<0.001; Ftime=33.19, P<0.001).Compared with baseline, IOP was increased in the dexamethasone group at each time point after administration, and the differences were statistically significant (all P<0.001).The IOP of the control and SIS3 groups at weeks 1, 2, 3, 4 were significantly lower than that of the dexamethasone group (all P<0.001).HE staining showed that the iridocorneal angles of all groups were open with similar morphology of the TM structure.Masson staining showed that the positive expression area of collagen in the control group, dexamethasone group and SIS3 group was (9.57±2.91)%, (27.75±5.88)% and (11.67±3.78)%, respectively, with a statistically significant difference among the three groups ( F=25.91, P<0.001), and the positive expression area of collagen was significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.001).The fluorescence expression level of FN in the control group, dexamethasone group and SIS3 group was 8.00±1.92, 14.01±2.74 and 7.85±0.64, respectively, and the fluorescence expression level of Col-1 was 6.90±1.16, 14.36±3.19 and 4.90±0.88, respectively, with statistically significant differences among the three groups ( F=15.93, 30.29; both P<0.001), and the fluorescence expression levels of FN and Col-1 were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.01).Immunofluorescence staining and Western blot showed that the cultured primary cells expressed myocilin and the expression level of myocilin was significantly increased after dexamethasone induction, which was identified as HTMCs.There were statistically significant differences in the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins among different groups of cells ( F=8.22, 23.08, 8.78; all P<0.05), and the relative expression levels of FN, Col-1, and p-Smad3/Smad3 proteins were significantly lower in the control group and SIS3 group than in the dexamethasone group (all P<0.05). Conclusions:SIS3 reduces IOP by inhibiting p-Smad3, reducing extracellular matrix deposition in TM, and reducing fibrosis in the TM tissue.
9.The Effect of MAGE-A3 Gene on the Biological Behavior and Drug Resistance of Ovarian Cancer
Rumeng WANG ; Ning ZHANG ; Yanan JI
Journal of Practical Obstetrics and Gynecology 2025;41(2):150-157
Objective:To investigate the effects of knockdown and overexpression of melanoma-associated antigen-A3(MAGE-A3)gene on the biological behavior and cisplatin resistance of ovarian cancer cells.Methods:The expression level of MAGE-A3 mRNA and protein in ovarian cancer cells was detected.The knockdown cell lines were constructed and divided into control group,no-load(NC)group and sh MAGE-A3 group.The overex-pression cell lines were divided into control group,no-load(NC)group and OE-MAGE-A3 group.The effects of knockdown and overexpression of MAGE-A3 gene on the proliferation,migration,invasion and apoptosis of tumor cells were compared.The expression of p53,Survivin,breast cancer susceptibility gene 1(BRCA1)and MAGE-A3 protein was detected.The high expression cell lines were divided into control group,cisplatin group,shMAGE-A3 group and cisplatin+shMAGE-A3 group.The low expression cell lines were divided into control group,cisplatin group,OE-MAGE-A3 group and cisplatin+OE-MAGE-A3 group.The cell proliferation,invasion ability of each group of cells,as well as their effects on the mRNA and protein expression level of each gene were compared.Results:The mRNA and protein expression of MAGE-A3 was high in SKOV3 cells and low in A2780 cells.Com-pared with the control group and NC group,the shMAGE-A3 group had lower OD450 value,migration rate and in-vasion numbers,higher apoptosis rate,lower expression of MAGE-A3 and Survivin protein,and higher expression of BRCA1 and p53 protein.The results of OE-MAGE-A3 group compared with control group and NC group were opposite to those of shMAGE-A3 group.Compared with the control group,cisplatin group and sh-MAGE-A3 group,the cisplatin+sh-MAGE-A3 group had lower OD450 value and invasion number higher levels of p53 and BRCA1 mRNA and protein expression,and lower levels of Survivin mRNA and protein.The OD450 value and in-vasion number of cells in cisplatin+OE-MAGE-A3 group were higher than those in cisplatin group,but lower than those in control group and OE-MAGE-A3 group.The mRNA and protein expression levels of p53 and BRCA1 were higher than those in the control group and the OE-MAGE-A3 group,but lower than those in the cisplatin group.The expression levels of Survivin mRNA and protein were lower than those in the control group and the OE-MAGE-A3 group,and higher than those in the cisplatin group.Conclusions:Knockdown of MAGE-A3 expression can effectively inhibit the proliferation,migration and invasion of ovarian cancer cells,promote apoptosis and en-hance cisplatin sensitivity.On the contrary,overexpression of MAGE-A3 increases cell proliferation,migration and invasion,and reduced apoptosis,thereby conferring cisplatin resistance.
10.Establishment of nuclear grade prediction model for T1 clear cell renal cell carcinoma based on CT features and radiomics
Caiyong ZHAO ; Chao CHEN ; Weiwei LI ; Jie WANG ; Rumeng ZHENG ; Feng CUI
Chinese Journal of Oncology 2025;47(2):168-174
Objective:To investigate the clinical value of the prediction models constructed by CT based imaging features and radiomics for World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading in pre-operative patients with T1 clear cell renal cell carcinoma (ccRCC).Methods:Ninety patients with ccRCC diagnosed at Hangzhou Hospital of Traditional Chinese Medicine from January 2016 to December 2023 were enrolled as the training set, and 43 patients diagnosed at the Sir Run Run Shaw Hospital from January 2017 to December 2018 were enrolled as the external validation set. According to the WHO/ISUP grading system, grades Ⅰ and Ⅱ were defined as the low grade group, and grades Ⅲ and Ⅳ were defined as the high grade group. In the training set, 64 patients were in the low grade group and 26 patients in the high grade group. In the external validation set, 33 patients were in the low grade group and 10 patients in the high grade group. The multivariate logistic regression was used to establish an imaging factor model based on CT imaging features in the training set. The 3-dimensional regions of interest were manually contoured at the cortical phase of enhanced CT, and the radiomics features were extracted. Linear correlation between features and L1 regularization were used for feature selection, and then linear support vector classification was used to construct the radiomics model. After that, a combined diagnostic model of nomogram combining the radiomics score and imaging factors was constructed using multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of each model. The Delong test was used for comparison of the areas under the ROC curve.Results:The imaging factor model, the radiomics model, and the combined diagnostic model of nomogram were successfully constructed to predict the WHO/ ISUP grading in stage T1 ccRCC. The AUC value of the imaging factor model in the training and validation sets was 0.742 (95% CI: 0.623-0.860) and 0.664 (95% CI: 0.448-0.879), respectively. The AUC values of the radiomics model in the two sets were 0.914 (95% CI: 0.844-0.983) and 0.879 (95% CI: 0.718-1.000), and of the combined diagnostic model of nomogram in the two sets were 0.929 (95% CI: 0.858-0.999) and 0.882 (95% CI: 0.710-1.000), respectively. The AUCs of the radiomics model and combined diagnostic model of nomogram were significantly higher than that of the imaging factor model (both P<0.05). There was no statistical difference in the AUCs between the combined diagnostic model of nomogram and the radiomics model (both P>0.05). Conclusion:The CT-based radiomics model and combined diagnostic model of nomogram incorporating radiomics signature and imaging features showed favorable predictive efficacy for the preoperative prediction of WHO/ISUP grading in stage T1 ccRCC.

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