1.USP20 as a super-enhancer-regulated gene drives T-ALL progression via HIF1A deubiquitination.
Ling XU ; Zimu ZHANG ; Juanjuan YU ; Tongting JI ; Jia CHENG ; Xiaodong FEI ; Xinran CHU ; Yanfang TAO ; Yan XU ; Pengju YANG ; Wenyuan LIU ; Gen LI ; Yongping ZHANG ; Yan LI ; Fenli ZHANG ; Ying YANG ; Bi ZHOU ; Yumeng WU ; Zhongling WEI ; Yanling CHEN ; Jianwei WANG ; Di WU ; Xiaolu LI ; Yang YANG ; Guanghui QIAN ; Hongli YIN ; Shuiyan WU ; Shuqi ZHANG ; Dan LIU ; Jun-Jie FAN ; Lei SHI ; Xiaodong WANG ; Shaoyan HU ; Jun LU ; Jian PAN
Acta Pharmaceutica Sinica B 2025;15(9):4751-4771
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.
2.Expert Consensus for Thermal Ablation of Pulmonary Subsolid Nodules (2021 Edition).
Xin YE ; Weijun FAN ; Zhongmin WANG ; Junjie WANG ; Hui WANG ; Jun WANG ; Chuntang WANG ; Lizhi NIU ; Yong FANG ; Shanzhi GU ; Hui TIAN ; Baodong LIU ; Lou ZHONG ; Yiping ZHUANG ; Jiachang CHI ; Xichao SUN ; Nuo YANG ; Zhigang WEI ; Xiao LI ; Xiaoguang LI ; Yuliang LI ; Chunhai LI ; Yan LI ; Xia YANG ; Wuwei YANG ; Po YANG ; Zhengqiang YANG ; Yueyong XIAO ; Xiaoming SONG ; Kaixian ZHANG ; Shilin CHEN ; Weisheng CHEN ; Zhengyu LIN ; Dianjie LIN ; Zhiqiang MENG ; Xiaojing ZHAO ; Kaiwen HU ; Chen LIU ; Cheng LIU ; Chundong GU ; Dong XU ; Yong HUANG ; Guanghui HUANG ; Zhongmin PENG ; Liang DONG ; Lei JIANG ; Yue HAN ; Qingshi ZENG ; Yong JIN ; Guangyan LEI ; Bo ZHAI ; Hailiang LI ; Jie PAN
Chinese Journal of Lung Cancer 2021;24(5):305-322
"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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3. Effects of individual differences on the pharmacokinetics of capecitabine in cancer patients
Guofang XU ; Pan GAO ; Ping LIU ; Yaowen LAI ; Guanghui LI ; Yue ZHAO ; Yongling ZHANG ; Xiaosu LI ; Qi QI
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(3):305-311
AIM: To study the effects of individual differences (gender, age, body surface area, and body weight) on the pharmacokinetics of capecitabine in cancer patients in hoping of providing evidence for the rational use of capecitabine in clinic. METHODS: A total of 76 patients with various solid tumors were given a single dose of 0.6 g (0.15 g, 4 tablets) capecitabine in postprandial and blood samples were collected at multiple time points. The plasma concentration of capecitabine and its active metablolite, 5-fluorouracil (5-FU) were analyzed by HPLC-MS/MS and the pharmacokinetic parameters of the drugs were calculated by Phoenix WinNonlin7.0 software. RESULTS: Following oral administration, the C
4.Preliminary results of multicenter studies on ABO-incompatible kidney transplantation
Hongtao JIANG ; Tao LI ; Kun REN ; Xiaohua YU ; Yi WANG ; Shanbin ZHANG ; Desheng LI ; Huiling GAN ; Houqin LIU ; Liang XU ; Zhigang LUO ; Peigen GUI ; Xiangfang TAN ; Bingyi SHI ; Ming CAI ; Xiang LI ; Junnan XU ; Liang XU ; Tao LIN ; Xianding WANG ; Hongtao LIU ; Lexi ZHANG ; Jianyong WU ; Wenhua LEI ; Jiang QIU ; Guodong CHEN ; Jun LI ; Gang HUANG ; Chenglin WU ; Changxi WANG ; Lizhong CHEN ; Zheng CHEN ; Jiali FANG ; Xiaoming ZHANG ; Tongyi MEN ; Xianduo LI ; Chunbo MO ; Zhen WANG ; Xiaofeng SHI ; Guanghui PEI ; Jinpeng TU ; Xiaopeng HU ; Xiaodong ZHANG ; Ning LI ; Shaohua SHI ; Hua CHEN ; Zhenxing WANG ; Weiguo SUI ; Ying LI ; Qiang YAN ; Huaizhou CHEN ; Liusheng LAI ; Jinfeng LI ; Wenjun SHANG ; Guiwen FENG ; Gang CHEN ; Fanjun ZENG ; Lan ZHU ; Jun FANG ; Ruiming RONG ; Xuanchuan WANG ; Guisheng QI ; Qiang WANG ; Puxun TIAN ; Yang LI ; Xiaohui TIAN ; Heli XIANG ; Xiaoming PAN ; Xiaoming DING ; Wujun XUE ; Jiqiu WEN ; Xiaosong XU
Chinese Journal of Organ Transplantation 2020;41(5):259-264
Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.
5.Preliminary clinical experience of ipsilateral simultaneous pancreas and kidney transplantation
Lei ZHANG ; Zheng CHEN ; Junjie MA ; Jiali FANG ; Guanghui LI ; Lu XU ; Xingqiang LAI ; Wei YIN ; Yunyi XIONG ; Luhao LIU ; Li LI ; Rongxin CHEN ; Peng ZHANG ; Hailin XU ; Tao ZHANG ; Jiao WAN ; Guanghui PAN
Chinese Journal of Organ Transplantation 2019;40(5):266-271
Objective To preliminarily explore the clinical efficacy of ipsilateral simultaneous pancreas and kidney transplantation (SPK) .Methods Ipsilateral SPK was performed in 40 patients from September 2016 to August 2018 .During a follow-up period of 6 to 29 months ,we summarized the efficacy and complications of the technique .Results Up to now ,38 patients achieved an exceelent clinical efficacy with no major surgical complications .However ,two patients died of severe pneumonia .The postoperative serum levels of creatinine at 3 ,6 ,12 ,24 months were 107 ,102 ,107 ,110 umol/L ;creatinine clearance rate 64 ,67 ,64 ,63 ml/min;fasting glucose 4 .6 ,5 .1 ,4 .6 ,5 .2 mmol/L ;glycated hemoglobin 4 .8% , 5 .4% ,4 .9% ,5 .2% respectively .And 1/2-year pancrea and kidney graft survival rates both were 92% . Complications included kidney graft rejection (n= 11) ,pancreas graft rejection (n= 12) ,simultaneous renal & pancreas graft rejection (n=6) ,renal graft DGF (n=1) ,pulmonary infection (n=14) ,urinary tract infections (n=18) ,gastrointestinal bleeding (n=10) diarrhea (n=6) ,splenic venous thrombosis (n=2) ,incomplete ureteric obstruction of renal allograft (n=3) ,urine leakage (n=1) and pancreas allograft dysfunction (n= 2) .There were no severe surgical complications .After aggressive interventions ,all postoperative complications were cured and none required excision of kidney or pancreas .Conclusions Ipsilateral SPK has definite therapeutic efficacy and it is worth wider popularization .
6.Research progress and challenges of deep learning in medical image registration.
Maoyang ZOU ; Hao YANG ; Guanghui PAN ; Yong ZHONG
Journal of Biomedical Engineering 2019;36(4):677-683
With the development of image-guided surgery and radiotherapy, the demand for medical image registration is stronger and the challenge is greater. In recent years, deep learning, especially deep convolution neural networks, has made excellent achievements in medical image processing, and its research in registration has developed rapidly. In this paper, the research progress of medical image registration based on deep learning at home and abroad is reviewed according to the category of technical methods, which include similarity measurement with an iterative optimization strategy, direct estimation of transform parameters, etc. Then, the challenge of deep learning in medical image registration is analyzed, and the possible solutions and open research are proposed.
Deep Learning
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Diagnostic Imaging
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Image Processing, Computer-Assisted
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Neural Networks (Computer)
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Research
7.Long-term study of pathological changes of living renal grafts from elderly relatives in young recipients
Jiali FANG ; Zheng CHEN ; Junjie MA ; Guanghui LI ; Lu XU ; Lei ZHANG ; Wei YIN ; Xingqiang LAI ; Yuhe GUO ; Yirui ZHANG ; Guanghui PAN
Organ Transplantation 2019;10(2):175-
Objective To investigate the safety of young recipients undergoing living donor renal transplantation from elderly relative donors through long-term follow-up of the pathological changes. Methods According to the age of donors, 28 young recipients were divided into the observation group (
8. Purification and cultivation of mouse primary retinal microvascular pericytes based on pre-incubation
Guanghui LIU ; Cuihong LIN ; Tianye YANG ; Chaoyang XU ; Yongzheng ZHENG ; Li ZHAO ; Chun MENG ; Mingdong PAN
Chinese Journal of Experimental Ophthalmology 2019;37(10):774-778
Objective:
To establish a simple method for isolation, purification and cultivation of primary retinal microvascular pericytes (RMPs) from mice.
Methods:
Retinas were isolated from mice following with mechanical morcel, enzymatic digestion and filtration.The retinal fragments were incubated with low glucose DMEM with 20% fetal bovine serum after 24 hours pre-incubation.Differential digestion was used for purification of primary RMPs.Morphological examination of cells was performed by phase contrast microscopy, and further characterization was analyzed by immunocytochemistry.Functional assay was evaluated by the pericytes-endothelial cells (ECs) co-culture system.The treatment and use of experimental animals followed the regulations on the administration of experimental animals promulgated by the state science and technology commission.
Results:
Cells migrated out of fragments after 24 hours of incubation, and developed into small or large colonies gradually.The cells and their subpassages presented typical pericyte morphology with large irregular triangular cell bodies and multiple long processes.No contact inhibition was observed.Most cells uniformly expressed the cellular markers α-smooth muscle actin (α-SMA) and platelet-derived growth factor receptor-β (PDGFR-β), a few cells expressed the cellular markers glial fibrillary acidic protein (GFAP), but no cell expressed von Willebrand factor (vWF). The purity rate of RMPs was up to 97%.In the co-culture system, RMPs directly contacted with ECs to form the capillary-like cords in vitro.
Conclusions
A simple method for the isolation, purification cultivation of mouse RMPs is established, and active RMPs can be readily obtained by this method.
9. Outcomes of patients treated with drug-coated balloons for de novo large coronary vessels
Jing QIU ; Zhanying HAN ; Xi WANG ; Wenjie LU ; Liang PAN ; Guoju SUN ; Xiaofei QIN ; Zhengbin WANG ; Guanghui LIU ; Xule WANG ; Chunguang QIU
Chinese Journal of Cardiology 2019;47(6):452-456
Objective:
To evaluate the efficacy and safety of drug-coated balloons (DCB) for de novo large coronary vessels.
Methods:
One hundred and two patients were retrospectively enrolled in this study, there were 104 lesions with the reference lumen diameter of target vessel more than 2.8 mm and patients were treated with DCB in de novo lesions during May 2015 and July 2017 in our center. Coronary artery angiography and quantitative coronary angiography were performed in 82 (80.4%) patients at follow up period ((8.1±1.7) months post procedure). The endpoints were late lumen loss (LLL) at follow up,and major adverse cardiac events (MACE) including cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and stent or target lesion thrombosis at 12 months post procedure.
Results:
Ninety-eight lesions were treated with DCB only, 6 (5.9%) bailout drug-eluting stent (DES) were used because of severe coronary dissection, 2 patients (2.0%) received revascularization driven by acute ischemic events during hospitalization. Cutting balloons and NSE balloons were used in 65.4% (68/104) and 26.0% (27/104) lesions. The lesion length was (12.57±3.58) mm and the DCB length was (19.87±4.55) mm. The late lumen loss was (0.01±0.52) mm during angiographic follow up. The TLR rate and overall MACE rate was 3.9% (4/102) and 3.9% (4/102) and there was no death,MI and target lesion thrombosis at 12 months follow up.
Conclusion
DCB treatment for de novo large coronary vessels is effective and safe.
10.Effects of Buyang Huanwu Decoction on the Expression of MMPs and TIMPs in Cardiac Tissue of Viral Myocarditis Model Mice
Youfa QIN ; Guanghui ZHOU ; Chunyu PAN ; Yongkun ZHU ; Yufeng YANG ; Rong PU
China Pharmacy 2019;30(22):3084-3089
OBJECTIVE: To investigate the effects of Buyang huanwu decoction on the expression of MMPs and TIMPs in cardiac tissue of viral myocarditis (VMC) model mice. METHODS: Male BALb/c mice were randomly divided into control group, model group, positive control group [captopril, 100 mg/(kg·d)], Buyang huanwu decoction low-dose, medium-dose and high-dose groups [6, 18, 36 g/(kg·d)], with 24 mice in each group. Except for control group, other groups were given Coxsackie virus B3 once intraperitoneally to induce VMC model. After modeling, control group and model group were given constant volume of normal saline intragastrically; administration groups were given relevant medicine intragastrically; once a day, for consecutive 30 days. The general situation of mice in each group was observed. The day of inoculation was set at 0 d, heart mass to body mass ratio (HW/BW) was measured at 4, 10, 20, 30 d after inoculation. The morphological characteristics of myocardium were observed by HE staining, and the myocardial histopathological scores of myocardium were evaluated. The distribution of type Ⅰ and Ⅲ collagen in myocardium was observed by Abcam picrosirius red staining, and the ratio of type Ⅰ to Ⅲ collagen was calculated. At 30 d, relative expressions of MMP-1, MMP-3, MMP-9 and TIMP-1 in cardiac tissue were detected by Western blotting assay, and the ratio of MMPs to TIMPs was calculated. RESULTS: Compared with control group, mice in model group suffered from irritability, arch back, alleviation of stimulation response, reduction of body mass and even mental depression. Typical inflammatory changes and local interstitial hyperemia were observed in the myocardium, accompanied by a large number of lymphocyte infiltration and distribution of type Ⅰ and Ⅲ collagen. HW/BW (at different time points of 10-30 d), myocardial histopathological score (at different time points of 4-30 d), ratio of type Ⅰ and Ⅲ collagen (at different time points of 4-30 d), the expression of MMP-1 and MMP-9, ratio of MMPs to TIMPs were increased significantly, while the expression of MMP-3 and TIMP-1 were decreased significantly (P<0.05). Compared with model group, above symptoms of mice in administration groups were improved to different extents. HW/BW [at different time points of 10-30 d in administration groups (except for 10 d in Buyang huanwu decoction low-dose group)], myocardial histopathological score (at different time points of 10-30 d in administration groups), ratio of type Ⅰand Ⅲ collagen (at different time points of 4-10 d in positive control group and Buyang huanwu decoction high-dose group, at different time points of 20-30 d in Buyang huanwu decoction low-dose and medium-dose groups), the expression of MMP-1 (positive control group and Buyang huanwu decoction high-dose group) and MMP-9 (administration groups), ratio of MMPs to TIMPs (administration groups) were decreased significantly, while the expression of MMP-3 (positive control group, Buyang huanwu decoction low-dose and high-dose groups) and TIMP-1 (administration groups) were increased significantly (P<0.05). CONCLUSIONS: Buyang huanwu decoction can inhibit myocardial fibrosis of VMC model mice by inhibiting myocardial collagen hyperplasia, regulating the expression of MMPs and TIMPs, improving MMPs/TIMPs imbalance.

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