1.Expression of Diacylglycerol Acyltransferase 2 in Neuroblastoma and its Correlation with MYCN Expression
Yixi WU ; Rui PAN ; Yang YANG ; Liang FENG ; Weirui WU ; Zhenzhen FANG ; Weiwei QI ; Xia YANG
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(2):227-237
ObjectiveTo explore the key genes influencing diacylglycerol metabolism in neuroblastoma (NB), clarify the expression and clinical significance of diacylglycerol acyltransferase 2 (DGAT2) in NB, and provide a theoretical basis for the diagnosis and targeted therapy of NB. MethodsNB transcriptome data were obtained from GEO (GSE49710) and TCGA (TARGET-NBL) databases. Differentially expressed genes (DEGs) commonly upregulated in MYCN-amplified groups were screened, and the key gene DGAT2 was identified by intersecting the screened DEGs with the diacylglycerol metabolism-related gene set followed by prognostic analysis and comparison. The expression of DGAT2 was analyzed via the R2 database. The potential impact of DGAT2 on the immune microenvironment was explored by combining the single-cell dataset GSE137804. Immunohistochemistry (IHC) was used to detect the expression level of DGAT2 and its correlation with MYCN expression in 55 clinical NB tissues and mouse xenograft tumor tissues. ResultsA total of 907 DEGs commonly upregulated in the MYCN-amplified groups were screened, among which three DEGs were highly expressed in the diacylglycerol metabolism-related gene set (P<0.05). After comparison, DGAT2 was found to have the most significant impact on prognosis (HR=1.4, 95% CI:1.2,1.7; P=5.41×10-7). Survival analysis showed that patients with high DGAT2 expression had a significantly shorter overall survival. Single-cell analysis revealed that high expression of DGAT2 led to an immunosuppressive microenvironment in NB. IHC results showed that the expression of DGAT2 in NB tissues was significantly positively correlated with MYCN expression in the tumor tissue microarrays of clinical NB patients and the tissues of mouse ectopic xenograft tumors (rs=0.369 4,P<0.01). ConclusionsDGAT2 is highly expressed in MYCN-amplified NB, and may independently predict poor prognosis in NB patients. It is expected to become a diagnostic marker for NB and a potential therapeutic target for MYCN-amplified NB.
2.Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis
Jiaqi DING ; Shenjie ZHANG ; Qi LI ; Boyu XIA ; Jingjing WU ; Xu LU ; Chao HUANG ; Xiaomei YUAN ; Qingsheng YOU
The Korean Journal of Physiology and Pharmacology 2025;29(3):307-319
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.
3.Predictive value of dose-surface histogram for acute radiation proctitis in prostate cancer patients following radiotherapy
Xin ZHAO ; Mei-Liu YANG ; Xiao-Hui HAO ; Tian-Xiong WEI ; Qi ZHANG ; Hao-Yu CHANG ; Xiu-Xia WU
Medical Journal of Chinese People's Liberation Army 2025;50(1):44-49
Objective To evaluate the predictive value of dose-surface histogram(DSH)for radiation proctitis(RP)in prostate cancer(PCa)patients undergoing radiotherapy.Methods This prospective randomized controlled clinical trial included 380 PCa patients who underwent image-guided radiotherapy in the First Affiliated Hospital of Hebei Northern University from January 2018 to January 2023.Patients were randomly divided into observation group(n=200)and control group(n=180).The rectal dose distribution of patients in the two groups was evaluated by using DSH and dose-volume histogram(DVH),respectively.The receiver operating characteristic(ROC)curve was utilized to evaluate the predictive value of DSH for acute RP,with DVH serving as a reference.Results The difference was not statistically significant in clinical information such as age,KPS score,and body mass index(BMI)between the observation and control groups(P>0.05),as well as in acute RP incidence(P>0.05).There were significant differences in S40 and V40,S50 and V50,S60 and V60,S70 and V70,and S78 and V78 between the two groups(P<0.05).S40,S50,V40,and V50 showed low efficacy(P<0.001)in predicting acute RP at each level,with AUC≤0.700.S60 and V60 showed moderate efficacy(P<0.001)in predicting acute RP at each level,with AUC 0.700-0.900.S70,S78,V70 and V78 showed high efficacy(P<0.001)in predicting acute RP at each level,with AUC>0.900.Conclusions The predictive value of DSH for rectal toxicity in patients with PCa is basically consistent with that of DVH.It is expected to become a novel and valuable tool for evaluating radiotherapy plans in the future.
4.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.
5.Short-term efficacy of endoscopic submucosal dissection for early carcinoma in the remnant stomach
Ying ZHOU ; Qi JIANG ; Baisheng CHEN ; Xia WU ; Qiuli JIANG ; Nashan LI ; Xingyu WU ; Pinghong ZHOU ; Weifeng CHEN ; Jianwei HU
Chinese Journal of Clinical Medicine 2025;32(4):620-626
Objective To explore the short-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early carcinoma in the remnant stomach. Methods A retrospective study was conducted on 45 patients with early residual gastric cancer underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2014 to April 2024, with a total of 45 lesions. The patients were divided into an anastomotic group (n=15) and a non-anastomotic group (n=30) based on the location of tumor occurrence, and their clinical data, endoscopic diagnosis and treatment, and histopathological conditions were compared between the two groups. Results All 45 patients had lesions with redness and erosion. There were 9 cases of poor lifting of submucosal injection in the anastomotic group and 2 cases in the non-anastomotic group, respectively, and the difference was statistically significant (P<0.05). ESD surgery was performed on 13 lesions in the anastomotic group and 28 lesions in the non-anastomotic group, with surgery times of 80.00 (50.00, 100.00) min and 55.00 (43.75, 80.00) min, respectively. The difference in surgery time between the two groups was statistically significant (P=0.03). Among the 45 patients, ESD surgery achieved curative resection in 35 cases, including 11 cases in the anastomotic group and 24 cases in the non-anastomotic group, with no statistically significant difference. Conclusions Careful preoperative evaluation of early carcinoma in the remnant stomach is essential to prevent oversight. Lesions at anastomotic sites and suture lines present higher technical challenges for complete resection. ESD is safe and effective, with auxiliary traction technique available when necessary.
6.Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis
Jiaqi DING ; Shenjie ZHANG ; Qi LI ; Boyu XIA ; Jingjing WU ; Xu LU ; Chao HUANG ; Xiaomei YUAN ; Qingsheng YOU
The Korean Journal of Physiology and Pharmacology 2025;29(3):307-319
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.
7.Research on the application of deep learning based on conventional MRI in differentiating solitary fibrous tumors from schwannomas in the orbit
Jiliang REN ; Zehang NING ; Meng QI ; Zhipeng XIA ; Guoqing WU ; Ying YUAN
Chinese Journal of Radiology 2025;59(2):206-211
Objective:To explore the value of deep learning (DL) models based on conventional MRI in differentiating orbital solitary fibrous tumors (SFT) from schwannomas.Methods:This was a case-control study. A retrospective analysis was conducted on patients with pathologically confirmed orbital SFT and schwannoma admitted to Eye & ENT Hospital, Fudan University (institution 1) from December 2014 to January 2022 and Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine (institution 2) from July 2015 to May 2022. A total of 140 patients were included, with 104 patients from institution 1 comprising the training cohort for building DL models and 36 patients from institution 2 comprising the external validation cohort for assessing model performance. Based on the preoperative cross-sectional fat-suppressed T 2WI and contrast-enhanced T 1WI (ceT 1WI), tumor contours were outlined on all tumor-containing slices. Six diagnostic models were constructed using residual networks (ResNet) and split-attention residual networks (ResNeSt) with 18 layers (ResNet-18 and ResNeSt-18), based solely on individual T 2WI and ceT 1WI, as well as a combination of both. A radiology resident and an attending radiologist independently reviewed conventional MRI images to determine the tumor type. The performance of the DL models and radiologists in differentiating orbital SFT from schwannoma in the external validation cohort was evaluated using receiver operating characteristic curves, and the areas under the curves (AUC) were compared using the DeLong test. Results:In the external validation cohort, the AUC (95% CI) of the ResNet-18 models based on T 2WI, ceT 1WI, and their combination were 0.861 (0.719-1), 0.896 (0.774-1), and 0.885 (0.755-1), respectively, while the AUC (95% CI) of the ResNeSt-18 models were 0.889 (0.748-1), 0.872 (0.726-1), and 0.910 (0.801-1), respectively. Among these, the ResNeSt-18 model based on the combined sequences achieved the best performance in differentiating the two tumors. The AUC (95% CI) for the individual interpretation of the radiology resident and attending radiologist were 0.729 (0.571-0.887) and 0.771 (0.618-0.923), respectively. The AUC of the ResNeSt-18 model based on the combined sequences was statistically significantly higher than those of the resident and attending radiologist ( Z=1.96, P=0.049; Z=2.00, P=0.045). Conclusion:The ResNeSt-18 model based on conventional MRI can effectively differentiate orbital SFT from schwannoma, demonstrating better performance than those of the radiology resident and the attending radiologist.
8.Shaoyaotang Regulates Glucose Metabolism Reprogramming to Inhibit Macrophage Polarization Toward M1 Phenotype
Shaijin JIANG ; Hui CAO ; Dongsheng WU ; Bo ZOU ; Yiwen WANG ; Yiling XIA ; Erle LIU ; Qi CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):86-93
ObjectiveTo explore the regulation of Shaoyaotang on glucose metabolism reprogramming of macrophages and the mechanism of this decoction in inhibiting macrophage polarization toward the M1 phenotype. MethodsHuman monocytic leukemia-1 (THP-1) cells were treated with 100 ng·L-1 phorbol myristate acetate for induction of macrophages as the normal control group. The cells treated with 100 ng·L-1 lipopolysaccharide combined with 20 ng·L-1 interferon (IFN)-γ for induction of M1-type macrophages were taken as the M1 model group. M1-type macrophages were treated with the blank serum, Shaoyaotang-containing serum, 0.5 mol·L-1 2-deoxy-D-glucose (2-DG), and Shaoyaotang-containing serum + 2-DG, respectively. After intervention, the expression of CD86 and CD206 was examined by flow cytometry. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β were assessed by ELISA. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of hypoxia-inducible factor-1 alpha (HIF-1α), glucose transporter 1 (GLUT1), hexokinase 2 (HK2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3). ResultsCompared with that in the normal control group, the expression of CD86, the marker of M1-type macrophages, increased in the M1 model group and blank serum group (P<0.01), which indicated that the M1 inflammatory model was established successfully. In addition, the M1 model group was observed with up-regulated mRNA and protein levels of proinflammatory cytokines IL-6 and TNF-α and glycolysis-related factors HIF-1α, GLUT1, HK2, GAPDH, and PFKFB3 (P<0.01). Compared with the M1 model group, the Shaoyaotang-containing serum, 2-DG, and combined intervention groups showed decreased expression of CD86 (P<0.01), down-regulated mRNA and protein levels of proinflammatory factors IL-6 and TNF-α and glycolysis-related factors HIF-1α, GLUT1, HK2, GAPDH, and PFKFB3 produced by M1-type macrophages (P<0.01), increased expression of CD206 (marker of M2-type macrophages) (P<0.01), and elevated levels of IL-10 and TGF-β produced by M2-type macrophages (P<0.01). ConclusionShaoyaotang inhibits macrophage differentiation toward pro-inflammatory M1-type macrophages and promotes the differentiation toward anti-inflammatory M2-type macrophages by regulating glucose metabolism reprogramming. The evidence gives insights into new molecular mechanisms and targets for the treatment of ulcerative colitis with Shaoyaotang.
9.Shaoyaotang Regulates Glucose Metabolism Reprogramming to Inhibit Macrophage Polarization Toward M1 Phenotype
Shaijin JIANG ; Hui CAO ; Dongsheng WU ; Bo ZOU ; Yiwen WANG ; Yiling XIA ; Erle LIU ; Qi CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):86-93
ObjectiveTo explore the regulation of Shaoyaotang on glucose metabolism reprogramming of macrophages and the mechanism of this decoction in inhibiting macrophage polarization toward the M1 phenotype. MethodsHuman monocytic leukemia-1 (THP-1) cells were treated with 100 ng·L-1 phorbol myristate acetate for induction of macrophages as the normal control group. The cells treated with 100 ng·L-1 lipopolysaccharide combined with 20 ng·L-1 interferon (IFN)-γ for induction of M1-type macrophages were taken as the M1 model group. M1-type macrophages were treated with the blank serum, Shaoyaotang-containing serum, 0.5 mol·L-1 2-deoxy-D-glucose (2-DG), and Shaoyaotang-containing serum + 2-DG, respectively. After intervention, the expression of CD86 and CD206 was examined by flow cytometry. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β were assessed by ELISA. Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of hypoxia-inducible factor-1 alpha (HIF-1α), glucose transporter 1 (GLUT1), hexokinase 2 (HK2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3). ResultsCompared with that in the normal control group, the expression of CD86, the marker of M1-type macrophages, increased in the M1 model group and blank serum group (P<0.01), which indicated that the M1 inflammatory model was established successfully. In addition, the M1 model group was observed with up-regulated mRNA and protein levels of proinflammatory cytokines IL-6 and TNF-α and glycolysis-related factors HIF-1α, GLUT1, HK2, GAPDH, and PFKFB3 (P<0.01). Compared with the M1 model group, the Shaoyaotang-containing serum, 2-DG, and combined intervention groups showed decreased expression of CD86 (P<0.01), down-regulated mRNA and protein levels of proinflammatory factors IL-6 and TNF-α and glycolysis-related factors HIF-1α, GLUT1, HK2, GAPDH, and PFKFB3 produced by M1-type macrophages (P<0.01), increased expression of CD206 (marker of M2-type macrophages) (P<0.01), and elevated levels of IL-10 and TGF-β produced by M2-type macrophages (P<0.01). ConclusionShaoyaotang inhibits macrophage differentiation toward pro-inflammatory M1-type macrophages and promotes the differentiation toward anti-inflammatory M2-type macrophages by regulating glucose metabolism reprogramming. The evidence gives insights into new molecular mechanisms and targets for the treatment of ulcerative colitis with Shaoyaotang.
10.Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis
Jiaqi DING ; Shenjie ZHANG ; Qi LI ; Boyu XIA ; Jingjing WU ; Xu LU ; Chao HUANG ; Xiaomei YUAN ; Qingsheng YOU
The Korean Journal of Physiology and Pharmacology 2025;29(3):307-319
Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue.Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells.These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.


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