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.HJT-sRNA-m7 bencaosome modulates fibrosis progression in a silicosis mouse model
Jiahui CHANG ; Pengju REN ; Yunyi ZHOU ; Chengyu JIANG ; Yanli ZHANG
Basic & Clinical Medicine 2025;45(7):874-881
Objective To explore the role and mechanism of HJT-sRNA-m7(M7)bencaosome in a silicosis mouse model.Methods C57BL/6J mice were randomly divided into four groups:blank,control,negative control(NC)oligonucleotide,and M7 treatment(HJT-sRNA-m7 bencaosome)groups.After three rounds of pretreatment with HJT-sRNA-m7 bencaosome,all groups except the blank one were modeled via a single intratracheal exposure.Each mouse received 50 μL of a silica suspension at a dose of 200 mg/kg body weight via intratracheal instillation.From day 6 to day 26,the bencaosome was administered every other day via oral gavages.On day 28,pulmonary function tests were performed.Bronchoalveolar lavage fluid was collected for flow cytometry and cytokine analysis.The left lung was harvested for histopathological examination and Masson's trichrome staining to evaluate collagen fiber dep-osition.The right lung was used for hydroxyproline quantification to assess collagen accumulation.Results The re-sults of pulmonary function test,pathological analysis and hydroxyproline measurements all indicated that M7 ben-caosome treatment significantly alleviated silica-induced pulmonary fibrosis.Moreover,flow cytometry analysis of BALF confirmed that M7 bencaosome inhibited the silica-induced inflammatory response,that was supported by cy-tokine analysis.Conclusions HJT-sRNA-m7 bencaosome is quite effective to treat silicosis and inhibits mitigating pulmonary fibrosis progression in mouse models.
3.Network pharmacology-based screening and validation of tea-derived small molecules against lung cancer
Rui YANG ; Sifen DU ; Lehui JIANG ; Tian FU ; Pengju REN ; Chengyu JIANG ; Yanli ZHANG
Basic & Clinical Medicine 2025;45(7):939-946
Objective To screen the active chemical components with potential therapeutic effects against lung cancer in tea and to provide new insights into the treatment and prevention of lung cancer.Methods Based on net-work pharmacology,the main active components from 13 types of tea samples were analyzed using liquid chromatog-raphy-mass spectrometry(LC-MS).The targets of these small molecules were obtained from the BATMAN-TCM da-tabase to construct a"component-target-disease"network.Lung cancer-related disease targets were retrieved from the GeneCard and Malacard databases followed by Gene Ontology(GO)functional and KEGG pathway enrichment analyses of potential pharmacological targets.A protein-protein interaction(PPI)network was constructed using the STRING database.The molecular docking was employed to screen small molecules with potential anti-cancer ac-tivity,and their potential inhibition to proliferation of human non-small cell lung cancer cell line A549 and human large cell lung cancer cell line H460.Results A total of 37 active components and 429 targets were identified in tea,with 182 overlapping targets associated with lung cancer.GO analysis revealed that these targets were primarily involved in biological processes such as cell proliferation,response to stimuli,and metabolic processes.KEGG pathway analysis indicated that these targets were mainly enriched in the p53 signaling pathway,ErbB signaling pathway,and PI3K-Akt signaling pathway.PPI network analysis identified key targets including MAPK1,AKT1,SRC,MAPK3,and p53.Molecular docking screened coumestrol as a molecule capable of binding to human estro-gen receptor 2(ESR2),and its inhibitory effect on the proliferation of A549 and H460 cells was experimentally validated(P<0.000 1).Conclusions The active components in tea may intervene in the development and progres-sion of lung cancer through a multi-component,multi-target,and multi-pathway mechanism,The results suggests po-tential components against lung cancer in tea,which may be applied in the prevention of human lung cancer.
4.Construction and immunogenicity evaluation of bacterial-like particles vaccine for porcine transmissible gastroenteritis
Lili GAI ; Shouzhi SHENG ; Yanting ZHU ; Siqi LI ; Pengju ZHANG ; Yanlong CONG
Chinese Journal of Veterinary Science 2025;45(8):1642-1649,1671
We took the surface spike S protein of transmissible gastroenteritis virus(TGEV)as the research object.Based on the Gram-positive enhancer matrix(GEM)-anchor protein(PA)display platform,two kinds of bacteria-like particles(BLPs)with surface-displayed TGEV DA and S1 were prepared using the insect cell-baculovirus expression system.The results showed that the lev-els of IL-4,IFN-γ,IgG,IgA,and sIgA induced by 50 μg BLP-DA were higher than those of the 25μg group.The levels of IL-4,IFN-γ,and sIgA induced by 50 μg BLP-S1 were higher than those of the 25 μg group,while the levels of IgG and IgA were lower than those of the 25 μg group.Under the same dose,when the dose was 25 μg,the levels of IFN-γ,IgG,IgA,and sIgA induced by BLP-S1 were higher than those of BLP-DA,while the level of IL-4 was lower than that of BLP-DA.When the dose was 50 μg,the level of IgG induced by BLP-DA was higher than that of BLP-S1,while the other indicators were lower than those of BLP-S1.Under different immunization routes,the levels of IgA and sIgA in the gavage group were higher than those in the intramuscular injec-tion group,and the levels of some cytokines were significantly higher in the gavage group than in the intramuscular injection group at specific time points,but there was no significant difference in the levels of IgG antibodies.In conclusion,the two types of TGEV BLPs constructed in this study both have good immunogenicity and can induce cellular and humoral immunity in mice.When the immunization doses are the same,the immunogenicity of BLP-S1 is better than that of BLP-DA.
5.Construction and immunogenicity evaluation of bacterial-like particles vaccine for porcine transmissible gastroenteritis
Lili GAI ; Shouzhi SHENG ; Yanting ZHU ; Siqi LI ; Pengju ZHANG ; Yanlong CONG
Chinese Journal of Veterinary Science 2025;45(8):1642-1649,1671
We took the surface spike S protein of transmissible gastroenteritis virus(TGEV)as the research object.Based on the Gram-positive enhancer matrix(GEM)-anchor protein(PA)display platform,two kinds of bacteria-like particles(BLPs)with surface-displayed TGEV DA and S1 were prepared using the insect cell-baculovirus expression system.The results showed that the lev-els of IL-4,IFN-γ,IgG,IgA,and sIgA induced by 50 μg BLP-DA were higher than those of the 25μg group.The levels of IL-4,IFN-γ,and sIgA induced by 50 μg BLP-S1 were higher than those of the 25 μg group,while the levels of IgG and IgA were lower than those of the 25 μg group.Under the same dose,when the dose was 25 μg,the levels of IFN-γ,IgG,IgA,and sIgA induced by BLP-S1 were higher than those of BLP-DA,while the level of IL-4 was lower than that of BLP-DA.When the dose was 50 μg,the level of IgG induced by BLP-DA was higher than that of BLP-S1,while the other indicators were lower than those of BLP-S1.Under different immunization routes,the levels of IgA and sIgA in the gavage group were higher than those in the intramuscular injec-tion group,and the levels of some cytokines were significantly higher in the gavage group than in the intramuscular injection group at specific time points,but there was no significant difference in the levels of IgG antibodies.In conclusion,the two types of TGEV BLPs constructed in this study both have good immunogenicity and can induce cellular and humoral immunity in mice.When the immunization doses are the same,the immunogenicity of BLP-S1 is better than that of BLP-DA.
6.Chinese experts' consensus on principles of preoperative hair removal
Yiping MAO ; Jun ZHENG ; Lei LI ; Deyan YANG ; Bing ZHANG ; Lei YANG ; Wang JIA ; Peng KANG ; Hui JIAO ; Yun YANG ; Qi QI ; Shiqing FENG ; Xiao LONG ; Yuewei ZHANG ; Xiaohui WANG ; Lize WANG ; Yuan WEI ; Jichao ZHOU ; Minghui MAO ; Pengju XIN ; Hongyu TAN ; Dahong ZHANG ; Lianxin LIU ; Lei TAO ; Xietong WANG ; Xiaoning YUAN ; Mang CAI ; Li MU ; Fang DU ; Rongzhu CHEN ; Fengmao ZHAO ; Jiuzuo HUANG ; Mingzi ZHANG ; Jie ZHANG ; Baoguo WANG ; Kun WANG ; Fang LUO ; Jinhua ZHANG ; Nong HE ; Ling LYU ; Zhiyong ZONG
Chinese Journal of Nosocomiology 2025;35(10):1441-1449
To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.
7.Chinese experts' consensus on principles of preoperative hair removal
Yiping MAO ; Jun ZHENG ; Lei LI ; Deyan YANG ; Bing ZHANG ; Lei YANG ; Wang JIA ; Peng KANG ; Hui JIAO ; Yun YANG ; Qi QI ; Shiqing FENG ; Xiao LONG ; Yuewei ZHANG ; Xiaohui WANG ; Lize WANG ; Yuan WEI ; Jichao ZHOU ; Minghui MAO ; Pengju XIN ; Hongyu TAN ; Dahong ZHANG ; Lianxin LIU ; Lei TAO ; Xietong WANG ; Xiaoning YUAN ; Mang CAI ; Li MU ; Fang DU ; Rongzhu CHEN ; Fengmao ZHAO ; Jiuzuo HUANG ; Mingzi ZHANG ; Jie ZHANG ; Baoguo WANG ; Kun WANG ; Fang LUO ; Jinhua ZHANG ; Nong HE ; Ling LYU ; Zhiyong ZONG
Chinese Journal of Nosocomiology 2025;35(10):1441-1449
To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.
8.A fragile X syndrome family with epilepsy
Jian HUANG ; Yuanxia WU ; Kuan FAN ; Rui LIU ; Pengju ZHANG ; Lu HAN ; Yuanyuan YANG ; Jiapeng LIU ; Shirong LI ; Xiao HU
Chinese Journal of Nervous and Mental Diseases 2024;50(1):30-32
Fragile X syndrome(FXS)is caused by abnormal duplication and amplification of the FMR1 gene CGG.This article reports a pair of brothers diagnosed with FXS by genetic testing.Two patients,aged 15 and 14 years old respectively,both had clinical manifestations such as language disorders,intellectual disabilities,attention deficit disorder,autism spectrum disorder,and FXS's characteristic facial features.The proband had a rare late-onset epileptic seizure,which was well treated with levetiracetam,while his younger brother had no electroencephalogram abnormalities after repeated follow-up.This pair of cases suggests that the clinical phenotype of FXS has diversity and heterogeneity.
9.KAT8 promotes the proliferation of colorectal cancer cell lines by enhancing METTL3 expression
Pengju ZHANG ; Jie LI ; Mengdi ZHANG ; Shaoke SUN ; Yinzhe XU
Basic & Clinical Medicine 2024;44(7):931-939
Objective To investigate the role and mechanism of lysine acetyltransferase 8(KAT8)on the prolifera-tion of colorectal cancer cells.Methods The expression of KAT8 in cancerous tissues and adjacent tissues of color-ectal cancer patients was analyzed by RNA-seq data of TCGA database.Cell proliferation was detected by colony-forming unit assays and CCK8.The GEO database was used to analyze the differential genes of KAT8 knockdown cells and control cells and perform functional pathway enrichment analysis.In the colorectal cancer database hosted on cBioPortal,that conducted an analysis examining the correlation between KAT8 and genes in the regulation of N6-methyladenosine(m6A)modification.Western blot technique was employed to assess the protein expression lev-els of KAT8 and METTL3.Results Compared to human normal colorectal tissue,KAT8 was highly expressed in colorectal cancer(P<0.05).Knockdown or selective inactivation of KAT8 inhibited colorectal cancer cells prolifera-tion(P<0.05).In colorectal cancer cell lines,knocking down KAT8 reduced m6A modification levels(P<0.05).Knocking down KAT8 inhibited METTL3 expression(P<0.05).Over-expression of METTL3 reversed cell prolifera-tion which was inhibited by knockdown KAT8(P<0.05).Conclusions KAT8 facilitates the proliferation of color-ectal cancer cell lines through regulation of METTL3-mediated m6A modifications.
10.Study on the Expression of Tissue STAT3 and Serum STAT3 mRNA,IL-12p40 and IL-13R α 2 Levels in Children with Congenital Intestinal Atresia and Their Correlation with Prognosis
Yanqing DONG ; Huizhong NIU ; Pengju ZHANG ; Hui REN ; Pan CHEN ; Zhiguang ZHANG ; Bobo NIU
Journal of Modern Laboratory Medicine 2024;39(5):35-40,46
Objective To investigate the expression of tissue signal transducer and activator of transcription 3(STAT3)and serum STAT3 mRNA,IL-12p40 and IL-13R α 2 levels in children with congenital intestinal atresia and their correlation with prognosis.Methods From January 2020 to January 2023,100 cases of intestinal atresia lesion tissues,normal intestinal tissues and preoperative serum samples were collected from children with congenital intestinal atresia who underwent treatment in Hebei Children's Hospital.According to the Grosfeld typing criteria,these children were categorized into 39 cases of type Ⅰ,22 cases of type Ⅱ,30 cases of type Ⅲ and 9 cases of type Ⅳ.Based on the recovery situation at 6 months after surgery,these children were separated into a good prognosis group(n=78)and a poor prognosis group(n=22).Serum samples from 93 cases of healthy children undergoing medical examinations during the same period were regarded as control samples.Immunohistochemistry was applied to detect the positive expression and localization of STAT3 in tissues.Western blot was applied to detect the expression of STAT3 protein in tissues,and quantitative polymerase chain reaction(qPCR)was applied to detect the expression level of STAT3 mRNA in serum.Pearson correlation was applied to analyze the correlation between serum STAT3 and inflammatory factor levels in children with congenital intestinal atresia.Logistic regression was used to analyze the factors affecting the prognosis of children with congenital intestinal atresia.Receiver operating characteristic(ROC)curve was applied to analyze the predictive efficacy of serum STAT3 level on the prognosis of children with congenital intestinal atresia.Results Immunohistochemical results showed that STAT3 positive expression was mainly localized in the cytoplasm and nucleus.The positive expression rate in congenital intestinal atresia tissue(86%)was higher than that in normal intestinal tissue(18%),and the difference was significant(x2=92.628,P<0.05).Western blot results showed that the relative expression level of STAT3 in congenital intestinal atresia tissue(1.59±0.21)was higher than that in normal intestinal tissue(0.81±0.12),and the difference was significant(t=30.567,P<0.05).The results of qPCR showed that serum STAT3(2.13±0.56),IL-12p40(0.89±0.13 ng/ml),and IL-13R α 2 levels(6.42±1.86ng/ml)in the congenital intestinal atresia group were higher than those in the control groups(1.06±0.11,0.37±0.08ng/ml,1.35±0.41ng/ml),and the differences were significant(t=18.101,33.170,25.708,all P<0.05).The levels of STAT3 and IL-12p40,IL-13R α 2 were gradually increased with the increase of the children's subtypes,and the differences were significant(F=52.666,160.300,25.82,all P<0.05).Pearson correlation analysis showed a positive correlation between serum STAT3,IL-12p40,and IL-13R α 2 levels in children with congenital intestinal atresia(r=0.496,0.564,all P<0.001).The expression level of serum STAT3 in poor prognosis group(3.01±0.75)was higher than that in good prognosis group(1.88±0.51),and the differences was statistically significant(t=8.212,P<0.05).Logistic regression showed that STAT3,IL-12p40,IL-13R α 2,and low birth quality were all independent risk factors for poor prognosis in children with congenital intestinal atresia(all P<0.05).The ROC curve showed that the area under the curve(AUC)for evaluating the prognosis of children with congenital intestinal atresia by serum STAT3 expression was 0.916,with a sensitivity of 81.82%and a specificity of 88.46%,respectively.When the serum STAT3 mRNA level was higher than 2.47,children with congenital intestinal atresia had a higher probability of poor prognosis.Conclusion The expression of STAT3 is increased in the tissues and serum of children with congenital intestinal atresia.Serum STAT3 may have a predictive value for the prognosis of affected children.

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