1.SAE1 promotes tumor cell malignancy via SUMOylation and liquid-liquid phase separation facilitated nuclear export of p27.
Ling WANG ; Jie MIN ; Jinjun QIAN ; Xiaofang HUANG ; Xichao YU ; Yuhao CAO ; Shanliang SUN ; Mengying KE ; Xinyu LV ; Wenfeng SU ; Mengjie GUO ; Nianguang LI ; Shiqian QI ; Hongming HUANG ; Chunyan GU ; Ye YANG
Acta Pharmaceutica Sinica B 2025;15(4):1991-2007
Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.
2.Development and validation of a recognition and classification system for portal hypertensive gastropathy based on deep learning
Haowen GU ; Jie YANG ; Yong XIAO ; Xinyue WAN ; Wei HU ; Xianmu XIE ; Dingpeng HUANG ; Chengming YAO ; Xinliang SHI ; Shiqian LIU ; Li HUANG ; Chi ZHANG ; Biqing ZHENG ; Mingkai CHEN
Chinese Journal of Digestive Endoscopy 2025;42(10):789-795
Objective:To develop a deep learning-based system for real-time recognition and classification of portal hypertensive gastropathy (PHG) and evaluate its ability to assist junior endoscopists.Methods:A total of 2 848 gastroscopy images from 832 patients with liver cirrhosis were selected from Digestive Endoscopy Center databases of Renmin Hospital of Wuhan University, Wuhan Hospital of Traditional Chinese and Western Medicine, and the Second Hospital of Jingzhou from January 2015 to October 2023. This system referred to 3 endoscopic features of Baveno Ⅱ scoring system. Three models were developed respectively for gastric antral vascular ectasia (GAVE), mosaic-like pattern (MLP), and red marks (RM). The specific classification references were as follows: (1) GAVE model: 0 no, 1 yes; (2) MLP model: 0 no, 1 mild, 2 severe; (3) RM model: 0 no, 1 isolated, 2 fused. The classification results for endoscopic characteristics of PHG of 3 endoscopy experts were taken as the gold standard. The yolov8-m model was used for training. The training dataset, validation dataset, and test dataset were allocated at a ratio of 8∶1∶1. The test dataset was used to evaluate the performance of models and their auxiliary effects on endoscopists. The accuracy, recall, precision, specificity and Kappa coefficient were calculated. Results:The accuracy, recall, specificity of GAVE model were 96.0% (48/50), 87.5% (7/8) and 97.6% (41/42). There was no significant difference between its accuracy and the gold standard ( χ2=316.226, P=1.000). The precision of GAVE1 and GAVE0 were 87.5% (7/8) and 97.6% (41/42) respectively. The accuracy of MLP model was 84.1% (132/157), and there was no significant difference compared with the gold standard ( χ2=3.286, P=0.193). The precision and recall of MLP2 were 88.2% (15/17) and 75.0% (15/20). The precision and recall of MLP1 were 77.9% (60/77) and 88.2% (60/68). The precision and recall of MLP0 were 90.5% (57/63) and 82.6% (57/69). The accuracy of RM model was 87.9% (123/140), and there was no significant difference compared with the gold standard ( χ2=2.891, P=0.409). The precision and recall of RM2 were 94.7% (18/19) and 78.3% (18/23). The precision and recall of RM1 were 72.2% (26/36) and 81.3% (26/32). The precision and recall of RM0 were 92.9% (79/85) and 92.9% (79/85). The mean accuracy of the three junior endoscopists, with and without the assistance of the GAVE model, MLP model, and RM model, respectively increased from 95.3% to 99.3%, from 83.9% to 91.9%, and from 81.9% to 83.1%. The overall consistency analysis of the 3 junior endoscopists with the gold standard indicated that the consistency of the GAVE model before and after assistance was extremely strong (both an overall Kappa of 1.000); the consistency before assistance of the MLP model was moderate (with an overall Kappa of 0.601), which increased to extremely strong after assistance (with an overall Kappa of 0.964); and the consistency of the RM model before and after assistance was also relatively strong (with an overall Kappa of 0.792 before and 0.798 after). Conclusion:The deep learning system accurately identifies and classifies PHG features and significantly enhances diagnostic performance of junior endoscopists.
3.Development and validation of a recognition and classification system for portal hypertensive gastropathy based on deep learning
Haowen GU ; Jie YANG ; Yong XIAO ; Xinyue WAN ; Wei HU ; Xianmu XIE ; Dingpeng HUANG ; Chengming YAO ; Xinliang SHI ; Shiqian LIU ; Li HUANG ; Chi ZHANG ; Biqing ZHENG ; Mingkai CHEN
Chinese Journal of Digestive Endoscopy 2025;42(10):789-795
Objective:To develop a deep learning-based system for real-time recognition and classification of portal hypertensive gastropathy (PHG) and evaluate its ability to assist junior endoscopists.Methods:A total of 2 848 gastroscopy images from 832 patients with liver cirrhosis were selected from Digestive Endoscopy Center databases of Renmin Hospital of Wuhan University, Wuhan Hospital of Traditional Chinese and Western Medicine, and the Second Hospital of Jingzhou from January 2015 to October 2023. This system referred to 3 endoscopic features of Baveno Ⅱ scoring system. Three models were developed respectively for gastric antral vascular ectasia (GAVE), mosaic-like pattern (MLP), and red marks (RM). The specific classification references were as follows: (1) GAVE model: 0 no, 1 yes; (2) MLP model: 0 no, 1 mild, 2 severe; (3) RM model: 0 no, 1 isolated, 2 fused. The classification results for endoscopic characteristics of PHG of 3 endoscopy experts were taken as the gold standard. The yolov8-m model was used for training. The training dataset, validation dataset, and test dataset were allocated at a ratio of 8∶1∶1. The test dataset was used to evaluate the performance of models and their auxiliary effects on endoscopists. The accuracy, recall, precision, specificity and Kappa coefficient were calculated. Results:The accuracy, recall, specificity of GAVE model were 96.0% (48/50), 87.5% (7/8) and 97.6% (41/42). There was no significant difference between its accuracy and the gold standard ( χ2=316.226, P=1.000). The precision of GAVE1 and GAVE0 were 87.5% (7/8) and 97.6% (41/42) respectively. The accuracy of MLP model was 84.1% (132/157), and there was no significant difference compared with the gold standard ( χ2=3.286, P=0.193). The precision and recall of MLP2 were 88.2% (15/17) and 75.0% (15/20). The precision and recall of MLP1 were 77.9% (60/77) and 88.2% (60/68). The precision and recall of MLP0 were 90.5% (57/63) and 82.6% (57/69). The accuracy of RM model was 87.9% (123/140), and there was no significant difference compared with the gold standard ( χ2=2.891, P=0.409). The precision and recall of RM2 were 94.7% (18/19) and 78.3% (18/23). The precision and recall of RM1 were 72.2% (26/36) and 81.3% (26/32). The precision and recall of RM0 were 92.9% (79/85) and 92.9% (79/85). The mean accuracy of the three junior endoscopists, with and without the assistance of the GAVE model, MLP model, and RM model, respectively increased from 95.3% to 99.3%, from 83.9% to 91.9%, and from 81.9% to 83.1%. The overall consistency analysis of the 3 junior endoscopists with the gold standard indicated that the consistency of the GAVE model before and after assistance was extremely strong (both an overall Kappa of 1.000); the consistency before assistance of the MLP model was moderate (with an overall Kappa of 0.601), which increased to extremely strong after assistance (with an overall Kappa of 0.964); and the consistency of the RM model before and after assistance was also relatively strong (with an overall Kappa of 0.792 before and 0.798 after). Conclusion:The deep learning system accurately identifies and classifies PHG features and significantly enhances diagnostic performance of junior endoscopists.
4.Relationship between self-esteem and mental health of medical students: mediating effect of psychological flexibility
Xin HUANG ; Xiaomeng MA ; Shiqian SUN ; Jiao LIU ; Xuemei LI
Chinese Journal of Medical Education Research 2023;22(3):457-462
Objective:To explore the relation among self-esteem, psychological flexibility and mental health in medical students, and to provide scientific reference for mental health education for medical students.Methods:A total of 788 medical students selected from a medical university in Chongqing City were investigated with the symptom checklist 90 (SCL-90), self-esteem scale (SES), acceptance and action questionnaire-Ⅱ (AAQ-Ⅱ), and cognitive fusion questionnaire-fusion (CFQ-F). SPSS 22.0 software was used for statistical analysis. T test, ANOVA, correlation analysis and tests for mediation effects were conducted. Results:There were significant differences in self-esteem and mental health level among medical students in gender and different grades ( t=-2.55, P<0.05; F=6.53, P<0.05). Mental health, self-esteem and psychological flexibility of medical students were correlated in pairs ( r=-0.528-0.694, P<0.01). Psychological flexibility played a partial mediation role between self-esteem and mental health of medical students, and the mediating effect accounted for 60.03% of the total effect. Conclusion:Self-esteem can directly predict the mental health of medical students, and can also indirectly affect mental health through psychological flexibility. Medical universities should carry out psychological education and promotion work with pertinence.
5.Application progress of ultrasound monitoring of diaphragm function in clinic
Xiang WANG ; Shiqian HUANG ; Zuhe XIA ; Shanglong YAO ; Haifa XIA
Chinese Critical Care Medicine 2021;33(5):638-640
In recent years, point of care ultrasound (POCUS) has developed rapidly in the fields of anesthesia and critical care. POCUS is widely used in clinic to monitor the function of human tissues and organs such as the heart, lungs, and diaphragm due to its visual, non-invasive, portable, and repeatable characters at the bedside. Diaphragm is an important structure to maintain respiratory function. Diaphragm paralysis or dysfunction can cause a significant decrease in inspiratory function. The patient's diaphragm function can be assessed through monitoring diaphragm thickness and activity by POCUS, and combined with other clinical indicators, the patient's recovery of respiratory function can be comprehensively evaluated, and rapidly identify the pathological conditions, such as diaphragm paralysis, diaphragm atrophy, diaphragmatic hypoplasia and amyotrophic lateral sclerosis. Dynamic evaluation of the process from diaphragmatic dysfunction to recovery can provide guidance for weaning and extubation, and real-time feedback on the treatment effect. This article reviews the ultrasound evaluation methods and clinical applications to the diaphragm, in order to guide clinicians to use relevant indicators to comprehensively evaluate the structure and function of the diaphragm, and then diagnose and treat diaphragm dysfunction, which may help making clinical decision.
6.Efficiency and safety of endoscopic therapy for early esophageal cancer and precancerous lesions with length more than 5 cm
Yangyang CHEN ; Yahua CHEN ; Shishun ZHONG ; Xinxiang HUANG ; Shiqian LAN ; Jianmin GUO ; Zicheng HUANG ; Caiping LI ; Yin LIN ; Wei LIANG
Chinese Journal of Digestive Endoscopy 2018;35(11):842-846
Objective To compare the effectiveness and safety of endoscopic submucosal dissection ( ESD) with endoscopic piecemeal mucosal resection ( EPMR) for early esophageal cancer and precancerous lesions with length more than 5 cm. Methods A retrospective analysis was performed on data of 85 patients diagnosed as early esophageal cancer and precancerous lesions with length more than 5 cm in Fujian Medical Association of Early Esophageal Carcinoma from January 2012 to July 2017. The patients were divided into ESD group (52 cases) and EPMR group (33 cases), and the effectiveness and safety between the two groups were compared. Results There was no significant difference on the complete resection rate between the two groups[86. 5% (45/52) VS 87. 9% (29/33), P>0. 05]. The operative time (58. 53±30. 50 min VS 32. 06±9. 12 min), postoperative fasting time (4. 18±1. 30 d VS 3. 67±0. 96 d), postoperative hospital-stay time (7. 45±2. 44 d VS 6. 54±1. 73 d), and postoperative antibiotics using time (3. 48±2. 33 d VS 1. 96±2. 20 d) in ESD group were higher than those in EPMR group (all P<0. 05). There were no significant difference in the rate of intraoperative complication and short-term postoperative complication, such as fever, chest pain, and postoperative bleeding, between the two groups ( all P>0. 05 ) . But the postoperative stricture rate of ESD group was higher than that of EPMR group[23. 1% (12/52) VS 6. 1%(2/33), P<0. 05]. During the follow-up of 3-63 months, 5 cases recurred in ESD group and 1 case in EPMR group, with no significant difference ( P>0. 05). Conclusion ESD and EPMR have equivalent efficacy and safety on the treatment of early esophageal cancer and precancerous lesion. EPMR has a shorter operative time, lower rate of post-operative stricture, and is easier to master.
7.Expression levels and mechanism of microRNA-34a and Notch1 signaling pathway in hippocampi of temporal lobe epilepsy rats
Baozhen YAO ; Tingting HUANG ; Hao YUAN ; Shiqian YU ; Haijyu ZHANG
Chinese Journal of Applied Clinical Pediatrics 2017;32(12):932-935
Objective To explore the expression levels of microRNA(miR)-34a in hippocampus of temporal lobe epilepsy rats and the effect of miR-34a on its target signaling pathway Notch1.Methods Rats were divided randomly into experiment group (n=40) and control group (n=40) by adopting random number table method.The status epilepticus model and the temporal lobe epilepsy model were induced by using lithium-pilocarpine for experiment group.The control group rats received an injection of an equal amount of 9 g/L saline as instead of pilocarpine.Racine grading was performed at 24 hours,day 3,day 7,day 15,and 1 month after modeling to evaluate the behavior.Real-time fluorescent quantitative polymerase chain reaction was used to test the mRNA expressions of miR-34a and Notch1.Western blot was performed to explore the protein expression of Notch1.Results The expression levels of miR-34a at post-status epilepticus in 24 hours,day 3,day 7,day 15 were 2.55±0.29,2.11±0.17,1.68±0.49 and 1.84±0.42,respectively,which showed statistically significant difference compared with the control group (1.00±0.00) (t=-1.55,-1.11,-0.68,-0.84,all P<0.05).The expression levels of Notch1 mRNA at post-status epilepticus in 24 hours,day 3,day 7,day 15,1 month were 1.44±0.31,1.27±0.13,1.52±0.28,0.91±0.33,and 0.80±0.09 respectively.There were significant differences at 24 hours,day 7 in Notch1 mRNA expression (t=-0.44,-0.52,all P<0.05) compared with the control group(1.00±0.00).The expression level of Notch1 mRNA on day 15 was significantly lower than 24 hours and day 7 (t=-0.54,-0.62,all P<0.05),and the expression in 1 month was significantly lower than in 24 hours,or day 3 and day 7 (t=-0.64,-0.46,-0.72,all P<0.05).The expression levels of Notch1 protein at post-status epilepticus 24 hours,day 3,day 7,day 15,1 month were 0.78±0.09,0.57±0.13,0.55±0.16,0.42±0.13,and 0.33±0.09,respectively.There was significantly up-regulated at 24 hours of Notch1 protein expression compared with control group (0.51±0.15)(t=-0.20,P<0.05);and the expression level at day 15 were significantly lower than 24 hours (t=-0.26,P<0.05),while the expression in 1 month was significantly lower than in 24 hours and on day 3 (t=-0.36,-0.24,all P<0.05).Conclusion miR-34a is significantly up-regulated in the post-status epilepticus rat hippocampus,and it may contribute to temporal lobe epilepsy by activating Notch1 signaling pathway.
8.Research Progress of Fertility-sparing Management in Young Endometrial Cancer Patients Based on ESGO Recommendations
Tingting CHEN ; Wenqian HUANG ; Shiqian ZHANG
Chinese Journal of Minimally Invasive Surgery 2017;17(1):80-83
[Summary] A more conservative approach for endometrial cancer ( EC ) is desirable in women who have requirement to preserve fertility, without compromising their survival .In this article, we tried to formulate clinical recommendations of preserving fertility based on suggestions of European Society of Gynaecological Oncology ( ESGO) in 2015 and relevant research progress .
9.Combination of fluorescence staining and dye dyeing for mapping sentinel lymph nodes in breast cancer patients
Hai LEI ; Xiaorong HUANG ; Sanling YAN ; Shiqian MIAO
Clinical Medicine of China 2015;31(12):1067-1070
Objective To evaluate intraoperative tracing of sentinel lymph node(SLN) by fluorescence staining combined with dye dyeing.Methods A total of 174 patients with breast cancer were randomly divided into three groups : the group A with 57 patients receiving methylene blue (MB), the group B with 58 patients receiving indocyanine green(ICG) as the lymphatic mapping tracers,the group C with 59 patients receiving MB and ICG.The sentinel and axillary lymph node of level Ⅱ, Ⅲ was excised, followed by conventional histopathology.Results There was no significant difference among the three groups in the term of visualized detection rate (x2=2.96, P =0.241).There was statistical significant difference among three groups in the term of detected lymph nodes(F=15.34, P<0.05).Comparing with the three groups, the number of detected lymph nodes of A and B group had no significant differences(P=0.07) ,the number of detected lymph nodes of C was higher than that of A and B group, and the difference was significant(P<0.05).There was statistical significant difference among three groups in the term of SLN positive rate (x2 =6.75, P =0.039), and there was no significant difference among A and B group(P=0.915) ,SLN positive rate of C group was higher than than A and B group, and the difference was statistical significant (P<0.05).Conclusion Intraoperative tracing of SLN by fluorescence staining combined with dye dyeing has the skin and subcutaneous reveal advantage.The use of ICG fluorescence and MB increases lymph node detection rate.
10.Separation and Purification of the Ethanol Extracts of Polygonum multiflorum and Study on Its Activity
China Pharmacy 2007;0(30):-
OBJECTIVE:To separate and purify the effective parts of the extracts of Polygonum multiflorum and study the activity of the effective parts.METHODS:The n-butanol extracts of P.multiflorum extracts were separated by silica gel column chromatography and eluted with different concentration of mixture of chloroform-methanol eluant gradiently,then the compounds were isolated by using ODS column and silica gel thin-layer preparation plate,and the effects of the compounds on the growth of human umbilical vein vascular endothelial cells were determined by MTT assay.RESULTS:A total of three compounds were isolated.The compounds could promote or inhibit the growth of human umbilical vein vascular endothelial cells.CONCLUSION:The established method is suitable for the separation and purification of the hydrophilic components of the ethanol extract of P.multiflorum.It is initially found out that the compounds that can promote the growth of human umbilical vein vascular endothelial cell were contained in P.multiflorum.

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