1.Discovery of a potential hematologic malignancies therapy: Selective and potent HDAC7 PROTAC degrader targeting non-enzymatic function.
Yuheng JIN ; Xuxin QI ; Xiaoli YU ; Xirui CHENG ; Boya CHEN ; Mingfei WU ; Jingyu ZHANG ; Hao YIN ; Yang LU ; Yihui ZHOU ; Ao PANG ; Yushen LIN ; Li JIANG ; Qiuqiu SHI ; Shuangshuang GENG ; Yubo ZHOU ; Xiaojun YAO ; Linjie LI ; Haiting DUAN ; Jinxin CHE ; Ji CAO ; Qiaojun HE ; Xiaowu DONG
Acta Pharmaceutica Sinica B 2025;15(3):1659-1679
HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.
2.Risk prediction of early esophageal varices in patients with liver cirrhosis based on interpretable machine learning
Yuheng YIN ; Yuwen WANG ; Jie FAN ; Chun YANG ; Wei WANG
Journal of Chongqing Medical University 2025;50(3):389-396
Objective:To investigate the risk factors for esophageal varices in patients with liver cirrhosis,to establish a predictive model,and to provide reasonable guidance for the prevention of early esophageal varices in patients with liver cirrhosis.Methods:A retrospective analysis was performed for 1 113 patients with liver cirrhosis who attended the hospitals in Chongqing,China from Decem-ber 2006 to May 2021.Recursive feature elimination(RFE)and four machine learning methods were used for the screening of features,and five machine learning predictive models were established by logistic regression,random forest,support vector machine(SVM),de-cision tree,and eXtreme Gradient Boosting(XGBoost).The receiver operating characteristic(ROC)curve was used to evaluate the per-formance of each model,and the model with the best performance was used to investigate the risk factors for esophageal varices in pa-tients with liver cirrhosis.SHAP plots were used to explain the impact of each risk factor on patients.Results:The XGBoost model showed the best performance in predicting the risk of esophageal varices in patients with liver cirrhosis,with an area under the ROC curve of 0.872(95%CI=0.813-0.918).SHAP plots showed that platelet count,diameter of the portal vein,cholinesterase,albumin,ala-nine aminotransferase,hemoglobin,prothrombin ratio,prothrombin time,and serum total protein were risk factors for esophageal vari-ces in patients with liver cirrhosis.Conclusion:This study shows that the XGBoost predictive model has a relatively high predictive value,and the risk factors obtained by this model have a certain guiding significance for the clinical prevention and treatment of early esophageal varices in patients with liver cirrhosis.
3.Relationship among physical activity,mild depressive symptoms and frontal alpha power asymmetry in college students
Xiang WANG ; Xiaojing ZHOU ; Shali QIU ; Yuheng ZANG ; Peng WANG ; Jing WANG ; Jinlei ZHAO ; Xin XIN ; Qun ZHAO ; Suowang YIN ; Xing WANG
Chinese Mental Health Journal 2024;38(2):180-185
Objective:To investigate the correlation among physical activity,mild depressive symptoms and frontal alpha power asymmetry in college students.Methods:Seventy college students with mild depressive symp-toms who conformed to the standard of the Self-Rating Scale for Depression(SDS)of 53-62 and 70 normal col-lege students were recruited.The frontal alpha power was measured under quiet and closed-eye state,and the total physical activity(PA)was assessed with the International Physical Activity Questionnaire.Results:The college students with mild depressive symptoms had lower Total PA scores,right frontal alpha power and frontal alpha a-symmetry(FAA)than the normal controls(P<0.001).In college students with mild depressive symptoms,the to-tal PA scores(r=-0.29,P<0.05)and FAA(r=-0.41,P<0.001)were negatively correlated with SDS scores,and the total PA scores were positively correlated with FAA(r=0.34,P<0.01).Conclusion:The college students with mild depressive symptoms may have reduced physical activity and asymmetric right lateralization of frontal alpha power.There is a correlation among depressive symptoms,physical activity and frontal alpha power a-symmetry in college students with mild depressive symptoms.
4.The key technology and Overall Architecture of Chinese Medicine Tongue Image Diagnostic System for Mobile Terminal
Shiqi ZHANG ; Junhan YANG ; Yuheng SUN ; Ni YIN ; Teng LI ; Haibo WU ; Shiyue GAO ; JiShi WANG ; Zhihui CHEN ; Xiangze LI ; Zhe ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(6):1618-1637
Tongue diagnosis is an important method of TCM diagnosis and treatment.Tongue is the key link of auxiliary diagnosis of tongue feature extraction and processing,and also is the bottleneck of intelligent tongue diagnosis in traditional Chinese medicine.Using image processing,artificial intelligence technology to the tongue as a quantitative and identify characteristics of traditional Chinese medicine,looking for both conforms to the original thinking of TCM,and TCM tongue diagnosis method of accurately,has become a common concern of traditional Chinese medicine and computer field.From the mobile terminal tongue as auxiliary diagnostic system of traditional Chinese medicine tongue acquisition basic attribute,tongue diagnosis and image information building,tongue like features are required for accurate extraction and so on related key technology is analyzed,and build overall architecture,so as to provide technical reference for the tongue like intelligent diagnosis,promote the development of technology of tongue diagnosis in traditional Chinese medicine modernization.
5.Research on magneto-acoustic-electrical tomography method based on liquid metal contrast agent and M sequence coded excitation.
Yuheng WANG ; Junjie LIN ; Wenshu MAI ; Zhipeng LIU ; Tao YIN ; Shunqi ZHANG
Journal of Biomedical Engineering 2023;40(4):718-724
Magneto-acoustic-electric tomography (MAET) boasts high resolution in ultrasound imaging and high contrast in electrical impedance imaging, making it of significant research value in the fields of early tumor diagnosis and bioelectrical monitoring. In this study, a method was proposed that combined high conductivity liquid metal and maximum length sequence (M sequence) coded excitation to improve the signal-to-noise ratio. It was shown that, under rotational scanning, the liquid metal significantly improved the signal-to-noise ratio of the inter-tissue magneto-acoustic-electric signal and enhanced the quality of the reconstructed image. The signal-to-noise ratio of the signal was increased by 5.6, 11.1, 21.7, and 45.7 times under the excitation of 7-, 15-, 31-, and 63-bit M sequence code, respectively. The total usage time of 31-bit M sequence coded excitation imaging was shortened by 75.6% compared with single-pulse excitation when the same signal-to-noise ratio was improved. In conclusion, the imaging method combining liquid metal and M-sequence coding excitation has positive significance for improving MAET image quality.
Contrast Media
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Electricity
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Electric Conductivity
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Acoustics
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Tomography
6.Effect of prone position ventilation on respiratory mechanics and prognosis in patients with acute respiratory distress syndrome concurrent with interstitial lung disease
Qingwen SUN ; Mangui ZHU ; Yin XI ; Yuheng YU ; Xuesong LIU ; Ling SANG ; Yonghao XU ; Sibei CHEN ; Lingbo NONG ; Weiqun HE ; Yuanda XU ; Yimin LI ; Xiaoqing LIU
Chinese Critical Care Medicine 2015;(10):785-790
ObjectiveTo explore the effect of prone position ventilation (PPV) on respiratory mechanics and prognosis in patients with acute respiratory distress syndrome (ARDS) concurrent with interstitial lung disease (ILD). Methods The data of 36 severe ARDS patients admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangzhou Medical University from February 2013 to January 2015, were retrospectively analyzed. They were then divided into two groups according to the presence of ILD or not. The changes in respiratory mechanics and oxygenation indexes were compared before and after PPV treatment in all the patients. Kaplan-Meier method was applied to draw the 60-day survival curves of both groups.Results There were 17 cases with ILD among these 36 severe ARDS patients.① No significant difference was found in baseline data between ILD group and non-ILD group.② Respiratory mechanics and oxygenation pre-PPV and post-PPV: compared with pre-PPV, oxygenation index (PaO2/FiO2, mmHg, 1 mmHg = 0.133 kPa) post-PPV was significantly increased in both groups [ILD group : 132.0 (93.5, 172.0) vs. 118.7 (92.0, 147.8); non-ILD group: 126.1 (100.9, 170.0) vs. 109.2 (89.0, 135.0), bothP< 0.05]. Compared with pre-PPV, positive end-expiratory pressure (PEEP, cmH2O,1 cmH2O = 0.098kPa) post-PPV was significantly higher in ILD group [10.0 (10.0, 12.0) vs. 10.0 (9.2, 12.0),P< 0.05], and respiratory rate (RR, times/min) was significantly lower in non-ILD group [24.5 (22.0, 27.0) vs. 25.5 (22.8, 28.0),P< 0.05]. The compliance of the respiratory system (Crs, mL/cmH2O) post-PPV in non-ILD group was significantly lower than that of the ILD group [19.7 (16.1, 28.6) vs. 23.0 (19.0, 29.7),P< 0.05].③ Respiratory mechanics and oxygenation pre-PPV and post-PPV in total: after all the PPV therapy, PaO2/FiO2 (mmHg) was significantly increased in non-ILD group [135.0 (86.0, 200.0) vs. 97.4 (69.2, 127.5), P< 0.05], PaO2/FiO2 after all the PPV therapy in non-ILD group was also higher than that in ILD group [135.0 (86.0, 200.0) vs. 78.7 (59.3, 114.9),P< 0.05]. No significant difference in Crs (mL/cmH2O) before PPV treatment was found between non-ILD and ILD groups [24.3 (15.9, 48.9) vs. 18.9 (12.7, 27.3),P> 0.05], and Crs was lower after PPV treatment in both groups, but without significant difference [non-ILD group: 22.7 (15.2, 27.1) vs. 24.3 (15.9, 48.9); ILD group: 16.2 (12.8, 25.6) vs. 18.9 (12.7, 27.3), bothP> 0.05].④ The 60-day mortality in ILD group was significantly higher than that in non-ILD group [88.2% (15/17) vs. 57.9% (11/19),P = 0.047). It was shown by Kaplan-Meier curves that 60-day survival patients in ILD group was significantly lower than those in non-ILD group (χ2 = 5.658,P = 0.017). Conclusions PPV can improve oxygenation in severe ARDS. Compared with non-ILD group, though the compliance of respiratory system in ILD group is increased during PPV, long-term effect is better in non-ILD group.
7.Influence of Electroacupuncture on COX Activity of Hippocampal Mitochondria in Senescence- accelerated Mouse Prone 8 Mice
Jing PENG ; Fang ZENG ; Yuheng HE ; Yong TANG ; Haiyan YIN ; Shuguang YU
Journal of Acupuncture and Tuina Science 2014;(4):199-202
Objective: To observe the effect of electroacupuncture (EA) on cytochrome c oxidase (COX)activity of hippocampal mitochondria in senescence-accelerated mouse prone 8 (SAMP8) mice, and to explore the EA mechanism on Alzheimer disease (AD) in improving energy metabolic disorder.
Methods: Twelve SAMP8 mice were randomly divided into a model group and an EA group, with six in each group. Six senescence-accelerated mouse resistance 1 (SAMR1) mice were prepared as blank group. Mice in the EA group received EA on Baihui (GV 20) and Yongquan (KI 1), once a day for 7 d as a course, altogether 3 courses with one day intervalbetween two courses. Mice in the model group and the blank group were manipulated and fixed as those in the EA group. After interventions, Morris water maze was employed to test spatial learning and memory ability to evaluate EA effect; spectrophotometry was used to detect the activity of hippocampal mitochondria COX.
Results: Compared with the blank group, mean escape latenciesof the EA group and model group were prolonged significantly in Morris water maze tests (P<0.01), the residue duration in the former platform quadrant significantly decreased (P<0.01). Compared with the model group, mean escape latencies on 1 d, 2 d and 3 d of the EA group were significantly reduced (P<0.05), and those on 4 d and 5 d continued the decreasing tendency (P<0.01), the residue duration on the former platform quadrant was significantly prolonged (P<0.05). The COX activity tests showed that, compared with the blank group, COX activities of the model group and the EA group were significantly decreased (P<0.01); compared with the model group, COX activity of the EA group was significantly elevated (P<0.01).
Conclusion: It’s plausible that EA improves AD learning and memory ability by increasing mitochondria COX activity, protecting the structure and function, and improving energy metabolism.

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