1.ALKBH3-regulated m1A of ALDOA potentiates glycolysis and doxorubicin resistance of triple negative breast cancer cells.
Yuhua DENG ; Zhiyan CHEN ; Peixian CHEN ; Yaming XIONG ; Chuling ZHANG ; Qiuyuan WU ; Huiqi HUANG ; Shuqing YANG ; Kun ZHANG ; Tiancheng HE ; Wei LI ; Guolin YE ; Wei LUO ; Hongsheng WANG ; Dan ZHOU
Acta Pharmaceutica Sinica B 2025;15(6):3092-3106
Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m1A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m1A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.
2.Research on the anti-tumor mechanism of toosendanin combined with olaparib in triple negative breast cancer
Huiqi HUANG ; Qiuyuan WU ; Kun ZHANG ; Peixian LI ; Yaming XIONG ; Guolin YE ; Dan ZHOU
Tianjin Medical Journal 2025;53(9):897-903
Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P<0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.
3.Research on the anti-tumor mechanism of toosendanin combined with olaparib in triple negative breast cancer
Huiqi HUANG ; Qiuyuan WU ; Kun ZHANG ; Peixian LI ; Yaming XIONG ; Guolin YE ; Dan ZHOU
Tianjin Medical Journal 2025;53(9):897-903
Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P<0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.
4.Expert consensus on the workflow of digital aesthetic design in prosthodontics
Zhonghao LIU ; Feng LIU ; Jiang CHEN ; Cui HUANG ; Xianglong HAN ; Wenjie HU ; Chun XU ; Weicai LIU ; Lina NIU ; Chufan MA ; Yijiao ZHAO ; Ke ZHAO ; Ming ZHENG ; Yaming CHEN ; Qingfeng HUANG ; Yi MAN ; Mingming XU ; Xuliang DENG ; Ti ZHOU ; Xiaorui SHI
Journal of Practical Stomatology 2024;40(2):156-163
In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.
5.Evaluation on the curative effect of digital subtraction angiography-guided radiofrequency ablation in patients with lumbar disc herniation based on infrared thermal imaging technology
Yaming LIU ; Zhongnan ZHAO ; Fanghui HUANG ; Shuaiyi LIU ; Yan JIAO ; Qinghai LYU
Journal of Clinical Surgery 2024;32(6):639-643
Objective To explore the evaluation on the curative effect of digital subtraction angiography(DSA)-guided radiofrequency ablation in patients with lumbar disc herniation(LDH)based on infrared thermal imaging technology.Methods A total of 90 patients with LDH treated in the hospital were enrolled as the research objects between February 2019 and February 2022.According to different treatment methods,they were divided into observation group(n=45)and control group(n=45).The control group was treated with radiofrequency ablation,while observation group was treated with DSA-guided radiofrequency ablation.The scores of visual analogue scale(VAS),Oswestry disability index(ODI)and Japanese Orthopaedic Association(JOA),and levels of serologic indexes[interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)]were compared between the two groups before treatment and at 1 month and 3 months after treatment.The skin temperature of lesions was detected by infrared thermal imaging,and its correlation with VAS,ODI and JOA scores was analyzed by Pearson correlation analysis.Results Before treatment,there was no significant difference in VAS score between the two groups(P>0.05).At 1 month and 3 months after treatment,VAS scores in both groups were decreased,which were lower in observation group than control group(P<0.05).Before treatment,there was no significant difference in ODI and JO A scores between the two groups(P>0.05).At 1 month and 3 months after treatment,ODI scores in both groups were decreased,which were lower in observation group than control group,while JOA scores were increased,which were higher in observation group than control group(P<0.05).Before treatment,there was no significant difference in levels of serum IL-1β,IL-6 and TNF-α between the two groups(P>0.05).At 1 month and 3 months after treatment,levels of serum IL-1 β,IL-6 and TNF-α in both groups were decreased,which were lower in observation group than control group(P<0.05).Before treatment,there was no significant difference in skin temperature of lesions between the two groups(P>0.05).At 1 month and 3 months after treatment,skin temperature of lesions in both groups was decreased,which was lower in observation group than control group(P<0.05).Pearson correlation analysis showed that skin temperature of lesions was positively correlated with VAS,ODI and JOA scores at 1 month and 3 months after treatment(r=0.455,0.502,0.523,0.675,0.659,0.611,P<0.05).Conclusion Curative effect of DSA-guided radiofrequency ablation is good on LDH patients,and infrared thermal imaging can effectively evaluate the curative effect.
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.Effect of Naples prognostic score on prognosis of hepatocellular carcinoma patients undergoing hepatectomy
Yaming XIE ; Lei LIANG ; Zunqiang XIAO ; Junwei LIU ; Chengwu ZHANG ; Dongsheng HUANG
Chinese Journal of Hepatobiliary Surgery 2024;30(5):341-346
Objective:To assess the impact of preoperative Naples prognostic score on the prognosis of patients with hepatocellular carcinoma (HCC) after hepatic resection.Methods:Retrospective analysis was conducted on the data of 323 patients with HCC who underwent radical hepatectomy in Zhejiang Provincial People's Hospital from January 2012 to December 2017, including 281 males and 42 females, aged (56.6±11.3) years. All patients were divided into three groups according to their preoperative Naples prognostic scores: group A (0) ( n=37), group B (1-2) ( n=193), group C (3-4) ( n=93). Survival was analysed by the Kaplan-Meier method, and differences in survival were compared by the log-rank test. Univariate and multivariate Cox regression were used to analyse the effect of Naples prognostic score on prognosis. Results:The 1-, 3- and 5-year cumulative survival rates of HCC patients after hepatectomy were 91.9%, 78.4% and 68.3% in the A group, 89.1%, 76.1% and 64.4% in the B group, and 84.9%, 63.3% and 43.5% in the C group, respectively, and the cumulative survival rates showed a decreasing trend among the three groups, and the differences were statistically significant (all P<0.05). The recurrence-free survival rates at 1, 3 and 5 years after hepatectomy were 93.4%, 63.3% and 44.3% in the A group, 77.7%, 46.5% and 35.6% in the B group, and 64.1%, 41.1% and 28.2% in the C group, respectively, and the recurrence-free survival rates showed a decreasing trend among the three groups, and the differences were statistically significant (all P<0.05). On Cox multivariate analysis, patients with HCC of 3-4 had a higher risk of death after hepatic resection than those patients of 0 ( HR=2.011, 95% CI: 1.048-3.859, P=0.036), and the risk of postoperative recurrence was also higher than those patients of 0 ( HR=1.820, 95% CI: 1.081-3.066, P=0.024). Conclusion:Preoperative Naples prognostic score performs as a prognostic influence factor on survival and recurrence-free survival after hepatectomy in patients with HCC.
8.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
9.Differences of brain gray matter volume and functional connectivity in adolescent female borderline personality disorder and correlation with dysregulation
Liping ZHANG ; Chunyan YIN ; Guoping HUANG ; Yaming HANG ; Ya XIE ; Pei ZHANG ; Yumin ZHANG ; Minlu LIANG ; Yun WU ; Chun WANG
Chinese Journal of Psychiatry 2023;56(5):354-360
Objective:To analyze the abnormal features of brain structure and functional connection (FC) in adolescent female patients with borderline personality disorder (BPD) and to explore the relationship between brain structure and clinical severity.Method:Eighteen female patients with BPD and 18 healthy controls matched with sex, age and education level aged 12—17 were examined by resting functional magnetic resonance imaging (fMRI). The differences of gray matter volume (GMV) and functional connection between the two groups were compared by voxel-based morphometric measurement and functional connection method, and t-test was used to compare the differences between the two groups. Spearman correlation analysis was used to analyze the correlation between abnormal brain regions, brain regions with different functional connections and Borderline Symptom List (BSL-23) scores. Result:The GMV of the left inferior temporal gyrus ( t=4.23), the right inferior temporal gyrus ( t=4.85), and the left middle orbital frontal gyrus ( t=4.16) were significantly larger in the BPD group than those in the healthy controls (GRF corrected voxel P<0.005, cluster P<0.05 two-tails). FC decreased in left inferior temporal gyrus and right middle temporal gyrus ( t=-6.20), increased in the left inferior temporal gyrus and the right fusiform gyrus ( t=5.75), the left inferior temporal gyrus and the left inferior parietal marginal angular gyrus ( t=4.38;GRF corrected voxel P<0.005, cluster P<0.05, two-tailed). In the BPD group, the increase in orbital frontal gray matter volume was negatively correlated with the emotional items BSL9 (tension; r=-0.523, P=0.023), BSL14 (rapid emotional changes; r=-0.549, P=0.018), BSL15 (tolerated pain; r=-0.589, P=0.010), BSL17 (vulnerable; r=-0.554, P=0.017), BSL5 (self-injury; r=-0.616, P=0.006) and BSL18 (suicide attraction; r=-0.661, P=0.003) in the BSL-23. Conclusion:There are differences in the GMV of the inferior temporal and the left middle orbital frontal lobe in adolescent female patients with BPD. The FC abnormalities of the left inferior temporal and right middle temporal gyrus, the left inferior temporal gyrus and the right fusiform gyrus, the left inferior temporal gyrus and the left inferior parietal marginal angular gyrus, especially the changes of GMV in the orbital frontal brain structure might participate in the pathological mechanism of emotion regulation injury in patients with BPD.
10.Differences of brain gray matter volume and functional connectivity in adolescent female borderline personality disorder and correlation with dysregulation
Liping ZHANG ; Chunyan YIN ; Guoping HUANG ; Yaming HANG ; Ya XIE ; Pei ZHANG ; Yumin ZHANG ; Minlu LIANG ; Yun WU ; Chun WANG
Chinese Journal of Psychiatry 2023;56(5):354-360
Objective:To analyze the abnormal features of brain structure and functional connection (FC) in adolescent female patients with borderline personality disorder (BPD) and to explore the relationship between brain structure and clinical severity.Method:Eighteen female patients with BPD and 18 healthy controls matched with sex, age and education level aged 12—17 were examined by resting functional magnetic resonance imaging (fMRI). The differences of gray matter volume (GMV) and functional connection between the two groups were compared by voxel-based morphometric measurement and functional connection method, and t-test was used to compare the differences between the two groups. Spearman correlation analysis was used to analyze the correlation between abnormal brain regions, brain regions with different functional connections and Borderline Symptom List (BSL-23) scores. Result:The GMV of the left inferior temporal gyrus ( t=4.23), the right inferior temporal gyrus ( t=4.85), and the left middle orbital frontal gyrus ( t=4.16) were significantly larger in the BPD group than those in the healthy controls (GRF corrected voxel P<0.005, cluster P<0.05 two-tails). FC decreased in left inferior temporal gyrus and right middle temporal gyrus ( t=-6.20), increased in the left inferior temporal gyrus and the right fusiform gyrus ( t=5.75), the left inferior temporal gyrus and the left inferior parietal marginal angular gyrus ( t=4.38;GRF corrected voxel P<0.005, cluster P<0.05, two-tailed). In the BPD group, the increase in orbital frontal gray matter volume was negatively correlated with the emotional items BSL9 (tension; r=-0.523, P=0.023), BSL14 (rapid emotional changes; r=-0.549, P=0.018), BSL15 (tolerated pain; r=-0.589, P=0.010), BSL17 (vulnerable; r=-0.554, P=0.017), BSL5 (self-injury; r=-0.616, P=0.006) and BSL18 (suicide attraction; r=-0.661, P=0.003) in the BSL-23. Conclusion:There are differences in the GMV of the inferior temporal and the left middle orbital frontal lobe in adolescent female patients with BPD. The FC abnormalities of the left inferior temporal and right middle temporal gyrus, the left inferior temporal gyrus and the right fusiform gyrus, the left inferior temporal gyrus and the left inferior parietal marginal angular gyrus, especially the changes of GMV in the orbital frontal brain structure might participate in the pathological mechanism of emotion regulation injury in patients with BPD.

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