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.Policy Analysis of Reimbursement Medical Consumables Catalogue and Payment Management in China
Yuzheng ZHANG ; Peimeng WANG ; Mengting JIA ; Yue LIU ; Xiaohui WANG ; Xue LI ; Yaoling WANG ; Rui LI ; Feiyi XIAO ; Lei ZHONG ; Xin GAO ; Xiaolu ZHANG ; Xuefei GU ; Wudong GUO
Chinese Health Economics 2025;44(2):34-40
Objective:To analyze the current situation of medical consumables management policy in China,and to provide a reference for the refined management of medical consumables.Methods:Through the policy triangle model and policy tool theory,it comprehensively analyzes the reimbursement medical consumables catalogue and payment management policy of medical insurance in China,covering the policy background,content,process,and participant dimensions.Results:The use frequency of medical consumables policy tools is not balanced,the payment management rules need to be refined,and the participation of multi-stakeholders such as patients is lacking.Conclusion:It is necessary to further strengthen the foundational management of reimbursement medical consumables catalogue,improve the access mechanism of medical consumables for medical insurance,and explore the formulation of categorized payment standards and innovative payment mechanisms.
3.The impact and potential mechanisms of Sorbs2 on the progression of ventricular arrhythmias in mice
Xiaolu ZHANG ; Fan YANG ; Huanhuan LIU ; Tianpeng WEI ; Yufei DAI ; Lei ZHANG ; Lingling QIAN ; Ruxing WANG
Chinese Journal of Cardiology 2025;53(8):922-930
Objective:To investigate the impact and potential mechanisms of Sorbin and SH3 domain-containing protein 2 (Sorbs2) on ventricular arrhythmias in mice.Methods:In the animal experiments, mating was performed using six 8-week-old Sorbs2 +/- mice (3 males and 3 females) weighing 20-22 g. Wild-type (Sorbs2 +/+, n=8) and homozygous (Sorbs2 -/-, n=6) offspring were selected as experimental subjects through genotyping. Echocardiography was performed at 16 weeks of age to record cardiac function parameters in both groups. Resting-state and caffeine-dobutamine-induced electrocardiograms were also conducted. Real-time quantitative reverse transcription polymerase chain reaction was used to detect Sorbs2 messenger RNA expression in the heart, liver, spleen, lung, kidney, brain, small intestine, and skeletal muscle tissues of wild-type mice. Western blotting was employed to measure the protein expression levels of Sorbs2 and voltage-dependent sodium channel alpha subunit 1.5 (Na v1.5) in myocardial tissues from both groups. In the cell experiments, H9C2 cells were transfected with Sorbs2 small interfering RNA as the si-Sorbs2 group, with a corresponding si-negative control group established. Western blot was performed to detect the protein expression levels of Sorbs2 and Na v1.5 in both groups. Results:Sorbs2 was abundantly expressed in cardiac tissue. Compared with wild-type mice, homozygous mice exhibited larger left ventricular end-systolic diameter, along with lower left ventricular ejection fraction and fractional shortening ( P all<0.05). Resting-state electrocardiograms revealed no spontaneous arrhythmias in either group; however, homozygous mice showed shorter RR intervals but longer QRS and QTc intervals versus wild-type mice ( P all<0.05). Following caffeine and dobutamine induction, homozygous mice demonstrated a higher incidence of ventricular arrhythmias, longer arrhythmia duration, and higher ventricular arrhythmia scores than wild-type mice ( P all<0.05). Western blot analysis revealed that Na v1.5 protein expression was markedly lower in myocardial tissues of homozygous mice compared to wild-type mice. Similarly, si-Sorbs2-transfected H9C2 cells exhibited lower Na v1.5 protein levels compared to the si-negative control group ( P<0.05). Conclusion:Sorbs2 plays a critical role in maintaining normal cardiac electrophysiological function. Deficiency of Sorbs2 may lead to impaired cardiac function and increased susceptibility to ventricular arrhythmias in mice, which could be associated with reduced expression of Na v1.5 protein.
4.Policy Analysis of Reimbursement Medical Consumables Catalogue and Payment Management in China
Yuzheng ZHANG ; Peimeng WANG ; Mengting JIA ; Yue LIU ; Xiaohui WANG ; Xue LI ; Yaoling WANG ; Rui LI ; Feiyi XIAO ; Lei ZHONG ; Xin GAO ; Xiaolu ZHANG ; Xuefei GU ; Wudong GUO
Chinese Health Economics 2025;44(2):34-40
Objective:To analyze the current situation of medical consumables management policy in China,and to provide a reference for the refined management of medical consumables.Methods:Through the policy triangle model and policy tool theory,it comprehensively analyzes the reimbursement medical consumables catalogue and payment management policy of medical insurance in China,covering the policy background,content,process,and participant dimensions.Results:The use frequency of medical consumables policy tools is not balanced,the payment management rules need to be refined,and the participation of multi-stakeholders such as patients is lacking.Conclusion:It is necessary to further strengthen the foundational management of reimbursement medical consumables catalogue,improve the access mechanism of medical consumables for medical insurance,and explore the formulation of categorized payment standards and innovative payment mechanisms.
5.The impact and potential mechanisms of Sorbs2 on the progression of ventricular arrhythmias in mice
Xiaolu ZHANG ; Fan YANG ; Huanhuan LIU ; Tianpeng WEI ; Yufei DAI ; Lei ZHANG ; Lingling QIAN ; Ruxing WANG
Chinese Journal of Cardiology 2025;53(8):922-930
Objective:To investigate the impact and potential mechanisms of Sorbin and SH3 domain-containing protein 2 (Sorbs2) on ventricular arrhythmias in mice.Methods:In the animal experiments, mating was performed using six 8-week-old Sorbs2 +/- mice (3 males and 3 females) weighing 20-22 g. Wild-type (Sorbs2 +/+, n=8) and homozygous (Sorbs2 -/-, n=6) offspring were selected as experimental subjects through genotyping. Echocardiography was performed at 16 weeks of age to record cardiac function parameters in both groups. Resting-state and caffeine-dobutamine-induced electrocardiograms were also conducted. Real-time quantitative reverse transcription polymerase chain reaction was used to detect Sorbs2 messenger RNA expression in the heart, liver, spleen, lung, kidney, brain, small intestine, and skeletal muscle tissues of wild-type mice. Western blotting was employed to measure the protein expression levels of Sorbs2 and voltage-dependent sodium channel alpha subunit 1.5 (Na v1.5) in myocardial tissues from both groups. In the cell experiments, H9C2 cells were transfected with Sorbs2 small interfering RNA as the si-Sorbs2 group, with a corresponding si-negative control group established. Western blot was performed to detect the protein expression levels of Sorbs2 and Na v1.5 in both groups. Results:Sorbs2 was abundantly expressed in cardiac tissue. Compared with wild-type mice, homozygous mice exhibited larger left ventricular end-systolic diameter, along with lower left ventricular ejection fraction and fractional shortening ( P all<0.05). Resting-state electrocardiograms revealed no spontaneous arrhythmias in either group; however, homozygous mice showed shorter RR intervals but longer QRS and QTc intervals versus wild-type mice ( P all<0.05). Following caffeine and dobutamine induction, homozygous mice demonstrated a higher incidence of ventricular arrhythmias, longer arrhythmia duration, and higher ventricular arrhythmia scores than wild-type mice ( P all<0.05). Western blot analysis revealed that Na v1.5 protein expression was markedly lower in myocardial tissues of homozygous mice compared to wild-type mice. Similarly, si-Sorbs2-transfected H9C2 cells exhibited lower Na v1.5 protein levels compared to the si-negative control group ( P<0.05). Conclusion:Sorbs2 plays a critical role in maintaining normal cardiac electrophysiological function. Deficiency of Sorbs2 may lead to impaired cardiac function and increased susceptibility to ventricular arrhythmias in mice, which could be associated with reduced expression of Na v1.5 protein.
6.Analysis for epitope polymorphism of class HLA-Ⅰ antigen from regular platelet donors in Nanjing area
Yu ZHANG ; Chengtao HE ; Jie CAI ; Lei LV ; Lu ZHANG ; Xiaolu HE ; Hailin DU ; Qiang FU ; Chun ZHANG
Chinese Journal of Clinical Laboratory Science 2024;42(10):738-743
Objective To investigate the characteristics of epitope distribution on HLA class Ⅰ antigen in the regular platelet donors from Nanjing area and establish the HLA epitope database for regular platelet donors.Methods High-resolution HLA typing was per-formed using Sanger method for the blood samples from 649 regular platelet donors in Nanjing area.The polymorphism of HLA antigen epitopes corresponding to the high-resolution HLA typing results was analyzed using the HLA Eplet Registry website.The frequencies of allele frequencies,HLA haplotype,and HLA antigen epitope were calculated by using the direct counting method.Results Among the 649 regular platelet donors,38 HLA-A alleles were detected,corresponding to 36 HLA-A epitopes,and the higher frequencies were 79GT,144K and 138MI.Seventy-three HLA-B alleles were detected corresponding to 35 HLA-B epitopes,and the higher frequencies were 131S,69TNT,and 80N.Sixty-four HLA class Ⅰ antigen epitopes were detected,in which the higher frequencies were 79GT,131S,and 144K.Conclusions The distribution of HLA antigen epitopes in the regular platelet donors of Nanjing area exhibited u-nique polymorphic characteristics.The epitope matching strategies should be established based on the distribution characteristics of HLA antigen epitopes,which may expand the range of available donors and reduce the incidence of platelet transfusion refractoriness.
7.circ_0084043/miR-31-5p Is Involved in Atherosclerosis by Regulating HMGA1:Investigation of the Mechanisms
Kehua WANG ; Ying LI ; Xiaolu REN ; Lei WANG
Journal of Sichuan University (Medical Sciences) 2024;55(6):1533-1542
Objective To explore the specific mechanism by which circ_0084043/miR-31-5p regulates high mobility group AT-hook 1(HMGA1)and thus participates in atherosclerosis(AS).Methods Carotid plaque tissues,diseased vascular tissue,and corresponding normal tissue from areas adjacent to the plaques were collected from 49 AS patients between September 2020 and September 2023.Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to determine circ_0084043 expression.The proliferation,migration,and invasion of vascular smooth muscle cells(VSMCs)induced by oxidized low-density lipoprotein(ox-LDL)were determined by CCK-8,clone formation,scratch,and Transwell assays.The targeted regulatory relationship among circ_0084043,miR-31-5p,and HMGA1 was verified by bioinformatics and dual luciferase reporter gene assay.An AS mouse model was established,and the pathological lesions in the aorta of AS model mice were observed by oil red O and HE stainings.Biochemical testing was performed to assess blood lipids in venous blood.qRT-PCR was used to determine the expression of miR-31-5p and HMGA1.Immunohistochemistry was performed to assess the expression of HMGA1 and α-smooth muscle actin(α-SMA)in the aorta of the AS model mice.Results In AS patients,the expression levels of circ_0084043 and HMGA1 in carotid plaque tissues and diseased vascular tissues were elevated(P<0.05),while the expression level of miR-31-5p was decreased(P<0.05).The expression of circ_0084043 was negatively correlated with the expression of miR-31-5p(r=-0.385 5,P=0.0062).HMGA1 expression was positively correlated with circ_0084043 expression(r=0.3317,P=0.0199),and negatively correlated with miR-31-5p(r=-0.3351,P=0.0186).MiR-31-5p had target binding sites for both circ_0084043 and HMGA1.Compared with the control group,the proliferation,clone formation,migration,and invasion abilities of the sh-NC group,the scramble group,the circ_0084043+miR-31-5p mimics group,the miR-31-5p inhibitor+sh-HMGA 1 group,and the circ_0084043+sh-HMGA1 group increased(P<0.05).In contrast,the proliferation,clone formation,migration,and invasion abilities of the sh-0084043 group significant decreased compared to those of the sh-NC group(P<0.05).The proliferation,clone formation,migration,and invasion abilities of the miR-31-5p mimics group and the sh-HMGA1 group decreased compared with those of the scramble group(P<0.05).Compared with the sh-NC group,sh-0084043 group had decreased aortic lipid plaque and necrotic core areas(P<0.05).Total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and the expression levels of HMGA1 mRNA and protein and α-SMA decreased(P<0.05),while high-density lipoprotein cholesterol(HDL-C)and miR-31-5p expression levels increased(P<0.05).Conclusion circ_0084043 promotes the proliferation and migration of VSMCs and promotes the progress of AS by inhibiting miR-31-5p and increasing the expression of HMGA1.
8.Semantic information retrieval based on the case report dataset of Adverse Drug Reactions Journal
Yayi XIAO ; Yi LEI ; Xin WANG ; Xiangrong BAI ; Qingxia ZHANG ; Xiaolu FEI
Adverse Drug Reactions Journal 2024;26(3):170-177
Objective:To explore the application value of semantic information retrieval (semantic retrieval) based on case reports dataset of Adverse Drug Reactions Journal. Methods:The dataset used in this study consists of 2 597 PDF files of case reports published on Adverse Drug Reactions Journal from 1999 to 2022. The semantic retrieval system is built by Baidu PaddlePaddle′s deep learning framework, the code was written in Python, and the text encoding model was Baidu RocketQA model. The precision at position k (P@k), recall at position k (R@k), mean reciprocal rank (MRR), mean average precision (MAP) and precision-recall (P-R) curve were used to evaluate the performance of semantic retrieval. The performance of semantic retrieval and keyword matching retrieval were compared by calculating the recall. Results:The set of preprocessed theme fields as items to be retrieved contained 2 597 documents, the set of search terms (queries) after removing deplicates and reorganizing included 1 388 drug name queries and 1 118 adverse reactions/events queries. The precision of drug name queries and adverse reactions/events queries by semantic retrieval were 0.667-1 and 0.566-1, and their recall were 0.667-0.871 and 0.566-0.863, respectively. The P-R curves of the top 1, 3, 5 and 10 documents in the semantic retrieval results using drug names queries and adverse reactions/events search terms showed that the precision decreased slowly in top 1 and 3 documents but significantly in top 5 and 10 documents with the increase of recall. The MRR of the 2 types of search terms were 0.854 and 0.871, and the MAP were 0.778 and 0.773, respectively. Using adverse reactions/events as search terms, semantic retrieval has a higher recall rate than keyword matching retrieval; using drug names as search terms, the recall rate of keyword matching retrieval is generally higher than that of semantic retrieval.Conclusions:The semantic retrieval system based on Baidu PaddlePaddle deep learning framework has good retrieval performance on the case reports dataset of Adverse Drug Reactions Journal. The semantic retrieval performs better with adverse reactions/events queries, while the keyword matching retrieval performs better with drug name queries.
9.Semantic information retrieval based on the case report dataset of Adverse Drug Reactions Journal
Yayi XIAO ; Yi LEI ; Xin WANG ; Xiangrong BAI ; Qingxia ZHANG ; Xiaolu FEI
Adverse Drug Reactions Journal 2024;26(3):170-177
Objective:To explore the application value of semantic information retrieval (semantic retrieval) based on case reports dataset of Adverse Drug Reactions Journal. Methods:The dataset used in this study consists of 2 597 PDF files of case reports published on Adverse Drug Reactions Journal from 1999 to 2022. The semantic retrieval system is built by Baidu PaddlePaddle′s deep learning framework, the code was written in Python, and the text encoding model was Baidu RocketQA model. The precision at position k (P@k), recall at position k (R@k), mean reciprocal rank (MRR), mean average precision (MAP) and precision-recall (P-R) curve were used to evaluate the performance of semantic retrieval. The performance of semantic retrieval and keyword matching retrieval were compared by calculating the recall. Results:The set of preprocessed theme fields as items to be retrieved contained 2 597 documents, the set of search terms (queries) after removing deplicates and reorganizing included 1 388 drug name queries and 1 118 adverse reactions/events queries. The precision of drug name queries and adverse reactions/events queries by semantic retrieval were 0.667-1 and 0.566-1, and their recall were 0.667-0.871 and 0.566-0.863, respectively. The P-R curves of the top 1, 3, 5 and 10 documents in the semantic retrieval results using drug names queries and adverse reactions/events search terms showed that the precision decreased slowly in top 1 and 3 documents but significantly in top 5 and 10 documents with the increase of recall. The MRR of the 2 types of search terms were 0.854 and 0.871, and the MAP were 0.778 and 0.773, respectively. Using adverse reactions/events as search terms, semantic retrieval has a higher recall rate than keyword matching retrieval; using drug names as search terms, the recall rate of keyword matching retrieval is generally higher than that of semantic retrieval.Conclusions:The semantic retrieval system based on Baidu PaddlePaddle deep learning framework has good retrieval performance on the case reports dataset of Adverse Drug Reactions Journal. The semantic retrieval performs better with adverse reactions/events queries, while the keyword matching retrieval performs better with drug name queries.
10.Study on the mechanism of FAK⁃PI3K/AKT signal pathway in the growth and development of neonatal rat cranial bone
Sixi Zhang ; Xiaolu Zhang ; Lei Wang ; Yubo Ma ; Guo Shao ; Chunyang Zhang
Acta Universitatis Medicinalis Anhui 2023;58(1):109-115
Objective:
To explore the growth characteristics of rat calvaria by detecting the calvaria of SD rats in different periods.
Methods:
The calvaria of SD rats at 1 , 4 , 7 , 10 , and 12 weeks from the same littermate were selected (3 rats per week) . Real⁃time PCR and Western blot techniques were used to detect the expression of focal adhesion kinase ( FAK) Ⅳ phosphatidylinositol 3 kinase/protein kinase B ( PI3K/AKT ) signal pathway in the calvaria , and the role of FAK⁃PI3K/AKT in the growth and development of the calvaria was analyzed by correlation.
Results:
The increase of brain volume and the thickness of calvaria increased synchronously , the expression of FAK was positively correlated with the changes of meridians , and the expression of FAK was positively correlated with the expression of PI3K/AKT.
Conclusion
The expression of FAK is related to the growth and development of rat skull. FAK plays a role in calvaria by activating PI3K/AKT signal pathway. FAK may be used as a marker of rapid skull growth and development , which provides a basic theoretical basis for the timing of clinical skull defect repair and treatment.


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