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.Gastrodin inhibits the lipopolysaccharide-induced microglia activation through the SOX2/β-catenin signaling pathway
Xinglin ZHANG ; Jinsha SHI ; Hongming FU ; Yurui HUANG ; Haolong SHI ; Hanjun ZUO ; Tao GUO ; Juanjuan LI
Chinese Journal of Neuroanatomy 2024;40(3):365-372
Objective:To investigate the effect of gastrodin(GAS)on the sex-determining region Y-box2(SOX2)/β-catenin pathway in microglia induced by lipopolysaccharide(LPS).Methods:BV2 microglia was cultured in vitro and divided into the following groups:Control group(Control),LPS group(LPS),LPS+0.17 mmol/L gastrodin treatment group(LPS+GAS-L),LPS+0.34 mmol/L gastrodin treatment group(LPS+GAS-H),SOX2 inhibitor pronethalolgroup(PR),LPS+PR group(LPS+PR),and LPS+PR+GAS group(LPS+PR+GAS).Effect of PR on BV2 microglia viability was detected by CCK-8.The expression of SOX2,β-catenin,mannose receptor(CD206)and tumor necrosis factor-α(TNF-α)was assessed using Western Blot and immunofluorescence double staining.Results:PR did not induce significant BV2 cell death in the 0~40 μmol/L range.After LPS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly increased in the LPS group,while CD206 decreased(P<0.05).Following GAS treatment,the expression levels of SOX2,β-catenin,and TNF-α significantly decreased,while CD206 increased(P<0.05).Compared to the LPS group,the expression levels of β-catenin and TNF-α significantly de-creased in the PR group(P<0.05),but no significant difference was observed between the LPS+GAS and LPS+PR+GAS group.Conclusion:GAS significantly inhibits LPS-induced microglia activation potentially through the inhibi-tion of the SOX2/β-catenin signaling pathway,and exerts anti-inflammatory effects.
3.A phase Ⅱ clinical study of the efficacy and safety of antaitasvir phosphate combined with yiqibuvir for the treatment of chronic hepatitis C in adults
Lai WEI ; Hongxin PIAO ; Jinglan JIN ; Shufen YUAN ; Xuan AN ; Jia SHANG ; Wenhua ZHANG ; Jiabao CHANG ; Tong SUN ; Yujuan GUAN ; Bo NING ; Jing ZHU ; Wentao GUO ; Qingwei HE ; Lin LUO ; Yulei ZHUANG ; Hongming XIE ; Yingjun ZHANG
Chinese Journal of Hepatology 2024;32(7):637-642
Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA
4.Accuracy and technical feasibility of mutual corroboration in the diagnosis of pulmonary nodule: A report of 1 368 cases
Guojun GENG ; Yanjun MI ; Xiaolei ZHU ; Guang ZHAO ; Ning LI ; Hongming LIU ; Weixi GUO ; Sien SHI ; Liangliang WANG ; Pan YIN ; Jie MA ; Xiuyi YU ; Jie JIANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(06):669-674
Objective By applying the mutual corroboration in the diagnosis, we aimed to improve the accuracy of preoperative imaging diagnosis, select the appropriate timing of operation and guide the follow-up time for patients with pulmonary nodules. Methods Clinical data of 1 368 patients with pulmonary nodules undergoing surgical treatment in our department from July 2016 to October 2019 were summarized. There were 531 males and 837 females at age of 44 (21-67) years. The intraoperative findings, images and pathology were classified and analyzed. The imaging pathology and pathological changes of pulmonary nodules were shown as a dynamic process through mutual collaboration and interaction. Results Of 1 368 patients with pulmonary nodules, 376 (27.5%) were pure ground-glass nodules, 729 (53.3%) were mixed ground-glass nodules and 263 (19.2%) were solid nodules. Among the pure ground-glass nodules, adenocarcinoma in situ (AIS) accounted for the highest proportion (156 patients), followed by microinvasive adenocarcinoma (MIA, 90 patients), atypical adenomatous hyperplasia (AAH, 85 patients), and benign tumors (20 patients). Among mixed ground-glass nodules, 495 patients were invasive adenocarcinoma (IA) and 207 patients of MIA. no patient was featured by AAH, AIS or MIA. Conclusion The mutual collaboration and interaction can improve the accuracy of preoperative diagnosis of pulmonary nodules, and it supports the choice of operation timing and the judgment of follow-up time.
5.Clinical characteristics and their relationships with glucose metabolism in elderly patients with Guil-lain-Barré syndrome
Lin GAO ; Daqiang QIN ; Jianhui XU ; Ying ZHU ; Xiaolin ZHANG ; Hongming GUO ; Ming YU
Journal of Chinese Physician 2017;19(12):1833-1835,1839
Objective To determine the clinical characteristics in elderly patients with Guillain-Barré syndrome ( GBS) and explore the relationship between glucose metabolism and severity and prognosis of disease. Methods Records of patients with GBS admitted between January 2004 and February 2017 from Affiliated Hospital of Jiangsu University were evaluated, including antecedent infection, initial symp-toms, cranial nerve palsy, subgroup analysis, Hughes score and Medical Research Council ( MRC) score at nadir and when discharged. Results The incidence of ocular palsy (6. 4% vs 27. 0%, P=0. 02) and of facial palsy (18. 8% vs 45. 8%, P =0. 016 ) were both lower in older group, compared to non-elderly group. MRC score at nadir (32 vs 44, P=0. 020), rate of severe type (80. 6% vs 47. 9%, P=0. 004) and rate of poor prognosis when discharged (67. 7% vs 29. 2%,P=0. 001) in elderly group were higher than non-elderly group. As to the distribution of subtype in these two groups, no significant difference was found (P=0. 691). Hyperglycemia wasn't prognostic factor of severe type (OR =0. 531,P =0. 321) or poor short-term prognosis (OR=0. 519,P=0. 261). Conclusions The clinical characteristics of elderly patients with GBS are distinct from non-elderly patients. Hyperglycemia wasn 't predictor of severe type or poor short-term prognosis of GBS.
6.Comparison of two surgical approaches for chronic subdural hematoma
Rulei GU ; Yao WEI ; Hongming JI ; Jianzhong GUO
Chinese Journal of Primary Medicine and Pharmacy 2017;24(9):1333-1337
Objective To compare the advantages and disadvantages of non-irrigation and irrigation in the surgical approach of chronic subdural hematoma (CSDH),thus to provide reference for clinical treatment of CSDH.Methods Clinical data of 102 patients with CSDH were retrospectively analyzed.According to the different operation methods,the patients were divided into the non-irrigation group(52 cases) and the irrigation group(50 cases).The blood loss during the procedure,operative time,length of stay and postoperative complication rate between the two groups were compared,and the causes of postoperative complications were analyzed.Results The blood loss during the procedure,operative time and length of stay in the non-irrigation group were (6.73 ± 1.17) mL,(15.06 ± 2.64) min and (10.74 ± 2.20) d,respectively,which in the irrigation group were (19.52 ± 3.18) mL,(38.54 ± 6.95) min and (10.44 ± 2.07)d,respectively,there were statistically significant differences between the two groups in the blood loss during the procedure and the operative time (t =-27.11,-22.72,all P < 0.05),there was no statistically significant difference between the two groups in the length of stay (t =0.70,P > 0.05).The incidence rates of postoperative complication in the non-irrigation group and irrigation group were 8.00% and 7.69%,respectively,there was no significant difference between the two groups (x2 =0.003,P > 0.05).Conclusion Each of the two methods has its own advantages and disadvantages in the treatment of CSDH.Compared with burr hole irrigation,burr hole non irrigation has the advantages of less blood loss and shorter operative time.However,burr hole non-irrigation is more likely to suffer serious complication.We should select suitable surgical approach by the specific circumstances of the patients.The causes of postoperative complications of CSDH are varied.In particular,there is an important relationship between the non-standard operation and postoperative complications.
7.Application of adaptive statistical iterative reconstruction in low dose temporal bone CT scan of children
Bin HE ; Ying GUO ; Ruijing YANG ; Hongming LIU ; Pengcheng WANG
Chinese Journal of Radiological Medicine and Protection 2016;36(7):544-547
Objective To evaluate clinical use of adaptive statistical iterative reconstruction (ASiR) method in low-dose scan on children temporal bone by comparison of radiation dose delivered by GE Discovert HD CT 750 scan and GE Lightspeed VCT64 scan.Method Sixty patients with congenital deafness were divided into two groups according to gender,age (each N =30).Group a received low-dose CT scan on temporal bone by GE Discovery HDCT 750 (preset NI =12),and the original images were reconstructed with ASiR (weighted value =40%).Group B received CT scan by GE Lightspeed VCT 64 (preset NI =8),and the original images were reconstructed with filter back projection (FBP).Data were collected and analysed using the SPSS 18.0 software.Resultes The mean value of electric current of average tube and CTDIvol were significantly different between group A and B [(110.40 ± 21.72) mA vs.(168.56±24.36) mA,and (26.43 ±3.48) mGy vs.(39.66 ±4.17) mGy,respectively (t=-9.76,-3.31,P<0.05)].The noise index was (33.13 ±2.68) in group A and (33.79 ±2.93) in group B respectively,and the results had no statistical significance (P > 0.05).Subjective scores of the images were (4.06 ± 0.03) and (4.05 ± 0.03),with no statistical significance either (P > 0.05).Conclusions On a condition of achieving same image quality,CT scan program using GE Discovery HD CT 750 with 40% ASiR reconstruction and 4 units NI value enhancement could effectively reduce radiation dose on children's temporal bone compared to FBP method using GE Lightspeed VCT 64.
8.The expression of the tryptase in the plasma of the brain traumatic patients
Jianzhong GUO ; Yao WEI ; Rulei GU ; Dongliang GUO ; Hongming JI
Chinese Journal of Primary Medicine and Pharmacy 2016;23(15):2275-2277
Objective To detect the expression of the tryptase in the plasma,and study the meaning in brain traumatic patients.Methods There were two groups:the brain traumatic group(40 patients)and the control group (20 health people).The content of plasma tryptase was determined by fluorescence enzyme immunoassay..Results The level of plasma tryptase had no statistical significance in control group(2.97 ±1.05)μg/L compared with the brain traumatic group(3.03 ±1.39)μg/L,however there had statistical significance comparing with sever brain traumatic patients(3.84 ±0.52μg/L)(t =3.32,P <0.05).4 cases of death in patients with severe head injury group content of tryptase (5.85 ±1.05)μg/L,which was significantly higher than the group of 16 cases of injury in severe head injury after 2 months still alive with the content of serum tryptase (2.49 ±0.52)μg/L,the difference was statistically significant (t =8.13,P <0.01).Conclusion The plasma tryptase level in sever brain traumatic patients increased significantly,and might be of importance for treatment strategies and prognosis.
9.Clinical diagnosis and treatment of inflammatory granuloma in central nervous system
Jianzhong GUO ; Yao WEI ; Hongming JI ; Gangli ZHANG ; Rulei GU
Chinese Journal of Primary Medicine and Pharmacy 2016;23(17):2617-2620
Objective To discuss the diagnosis and treatment of inflammatory granuloma in central nervous system(CNS)to provide reference for clinic.Methods Retrospective data included 8 patients with CNS inflammatory granuloma in Department of Neurosurgery,Shanxi People's Hospital,2012 -2015.We analyzed the imaging features, postoperative symptoms,blood and cerebrospinal fluid changes and prognosis.Results 8 cases all received surgical treatment.All the symptoms were improved,and the CT showed that the lesions were disappeared.All the patients had recovered to normal life and work.Conclusion The diagnosis of CNS inflammatory granuloma is difficult.Clinical manifestations are lack of specificity.The blood and cerebrospinal fluid laboratory examination have no abnormal changes.CT and MRI are the main diagnostic methods.Postoperative pathology is the gold standard for diagnosis.The large lesion,frequent episodes of epilepsy,severe neurological deficits and possibility of brain tumor all should be treated by surgery.
10.Surgical treatment of functional glioma by neuronavigation with intraoperative ultrasound
Yao WEI ; Hongming JI ; Yubo HE ; Jiuhong MA ; Rui CHENG ; Jianzhong GUO
Chinese Journal of Primary Medicine and Pharmacy 2015;(11):1643-1645
Objective To investigate the operation process,extent of resection,protection function,the tumor recurrence and clicical value of neuronavigation with intraoperative ultrasound for treating functional glioma;signifi-cance of intraoperative ultrasound for correcting brain shift.Methods We analyzed the cliclical materical of 24 case of functional gliomas which were resected by neuronavigation with intraoperative ultrasound.Results The accuracy of localization of functional glioma was 100%.The distance of brain shift was 2 to 10mm,with an average 4.7mm.After 24 hours MRI confirmed that total removal of function glioma was achieved in 21 cases,subtotal in 3 cases.After oper-ation function improve was 20 cases,invalid of 2 cases,hemiplegia happened in 2 cases and no death in all the patients.Conclusion Neuronavigation with intraoperative ultrasound can correct brain shift and improve the accuracy of localization of functional glioma,to improve extent of function glioma and decrease dysfunction.Neuronavigation with intraoperative ultrasound is important to functional glioma.

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