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.

Objective:To investigate the efficacy and safety of avatrombopag in promoting hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Method:A retrospective analysis was conducted on 60 recipients with hematological malignancies who underwent allo-HSCT at the Affiliated Hospital of Xuzhou Medical University from January 2022 to August 2023. Recipients with hepatic or renal insufficiency before conditioning, those who received other thrombopoietic agents after allo-HSCT, those with severe respiratory or circulatory system diseases, and those with a history of thromboembolic events were excluded. Among them, 30 recipients who received avatrombopag within 14 days post-transplantation were assigned to the avatrombopag group, while the remaining 30 recipients who did not receive any thrombopoietic agents served as the control group. Clinical characteristics, hematopoietic stem cell engraftment, bone marrow proliferation, transfusion requirements, transplant-related complications, and laboratory adverse events were compared between the two groups.Result:The median platelet engraftment time in the avatrombopag group was 13 days (range: 9~25 days), and the neutrophil engraftment time was 13 days (range: 11~21 days). In the control group, he platelet engraftment time was 15 days (range: 10~51 days), and neutrophil engraftment time was 14 days (range: 10~30 days). The difference in platelet engraftment time between the two groups was statistically significant ( P=0.039). Bone marrow analysis on day 28 post-transplant showed that the proportion of recipients with active bone marrow hyperplasia was 96.7% in the avatrombopag group and 73.3% in the control group ( P=0.030); the median number of megakaryocytes was 30 vs. 6, respectively ( P<0.001); and the proportion of mature platelet-producing megakaryocytes was 44% vs. 26.3% ( P<0.001). Regarding transfusion requirements, the median platelet transfusion volume within 28 days post-transplantation was 4.5 U (range: 2~16 U) in the avatrombopag group and 6.5 U (range: 3~32 U) in the control group ( P=0.007). The time to achieve platelet transfusion independence was 13 days (range: 8~25 days) in the avatrombopag group and 14 days (range: 10~36 days) in the control group ( P=0.026). The median red blood cell transfusion volume in both groups was 4 U, with no significant difference ( P=0.354). Medication adherence in the avatrombopag group was 100%. There were no statistically significant differences between the two groups in terms of incidence of post-transplant infections (70% vs. 83.3%), bleeding (50% vs. 60%), graft-versus-host disease (GVHD) (30% vs. 40%), or abnormal laboratory tests (86.7% vs. 90%) (all P>0.05). Conclusion:The use of avatrombopag after allo-HSCT in patients with hematologic malignancies can promote bone marrow hematopoiesis and platelet engraftment, reduce platelet transfusion volume, and shorten the duration of platelet transfusion dependence. Avatrombopag is well tolerated, and no serious adverse reactions were observed during treatment.

Objective:To investigate the efficacy and safety of avatrombopag in promoting hematopoietic reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Method:A retrospective analysis was conducted on 60 recipients with hematological malignancies who underwent allo-HSCT at the Affiliated Hospital of Xuzhou Medical University from January 2022 to August 2023. Recipients with hepatic or renal insufficiency before conditioning, those who received other thrombopoietic agents after allo-HSCT, those with severe respiratory or circulatory system diseases, and those with a history of thromboembolic events were excluded. Among them, 30 recipients who received avatrombopag within 14 days post-transplantation were assigned to the avatrombopag group, while the remaining 30 recipients who did not receive any thrombopoietic agents served as the control group. Clinical characteristics, hematopoietic stem cell engraftment, bone marrow proliferation, transfusion requirements, transplant-related complications, and laboratory adverse events were compared between the two groups.Result:The median platelet engraftment time in the avatrombopag group was 13 days (range: 9~25 days), and the neutrophil engraftment time was 13 days (range: 11~21 days). In the control group, he platelet engraftment time was 15 days (range: 10~51 days), and neutrophil engraftment time was 14 days (range: 10~30 days). The difference in platelet engraftment time between the two groups was statistically significant ( P=0.039). Bone marrow analysis on day 28 post-transplant showed that the proportion of recipients with active bone marrow hyperplasia was 96.7% in the avatrombopag group and 73.3% in the control group ( P=0.030); the median number of megakaryocytes was 30 vs. 6, respectively ( P<0.001); and the proportion of mature platelet-producing megakaryocytes was 44% vs. 26.3% ( P<0.001). Regarding transfusion requirements, the median platelet transfusion volume within 28 days post-transplantation was 4.5 U (range: 2~16 U) in the avatrombopag group and 6.5 U (range: 3~32 U) in the control group ( P=0.007). The time to achieve platelet transfusion independence was 13 days (range: 8~25 days) in the avatrombopag group and 14 days (range: 10~36 days) in the control group ( P=0.026). The median red blood cell transfusion volume in both groups was 4 U, with no significant difference ( P=0.354). Medication adherence in the avatrombopag group was 100%. There were no statistically significant differences between the two groups in terms of incidence of post-transplant infections (70% vs. 83.3%), bleeding (50% vs. 60%), graft-versus-host disease (GVHD) (30% vs. 40%), or abnormal laboratory tests (86.7% vs. 90%) (all P>0.05). Conclusion:The use of avatrombopag after allo-HSCT in patients with hematologic malignancies can promote bone marrow hematopoiesis and platelet engraftment, reduce platelet transfusion volume, and shorten the duration of platelet transfusion dependence. Avatrombopag is well tolerated, and no serious adverse reactions were observed during treatment.

Objective:To explore the genotype and clinical phenotype characteristics of patients with pancreatic agenesis caused by GATA6 gene mutations and to improve the clinical understanding of pancreatic agenesis.Methods:The clinical data of a newborn with pancreatic agenesis admitted to the Second Hospital of Shandong University were retrospectively analyzed. Relevant literature published until October 31, 2022, were retrieved from China National Knowledge Infrastructure, Wanfang Database, VIP Database, Chinese Medical Journal Full Text Database, PubMed, Embase and SCI Database with the terms of "pancreatic agenesis", "GATA6", "pancreatic agenesis/hypoplasia" and "GATA6 Translation Factor". The characteristics of gene variants and clinical manifestations of patients diagnosed with pancreatic agenesis caused by GATA6 gene mutation were retrieved and summarized.Results:This case was a full-term male infant who developed insulin dependent hyperglycemia and fatty diarrhea 2 d after birth, accompanied by intrauterine growth restriction, congenital heart disease, and cryptorchidism. Genetic testing showed a novel heterozygous mutation of GATA6 (c.1366C>T) which was consistent with the autosomal dominant inheritance pattern. The phenotype and genotype between the proband and his parents were consistent with the cosegregation. The ACMG mutation was rated as pathogenic variant. Intravenous infusion of insulin, subcutaneous injection of insulin, or long-acting insulin were not effective. After continuous subcutaneous pumping of aspartic insulin combined with oral pancreatic enzyme replacement therapy, the infant's condition was improved and discharged. Follow up to age of 15 months, the patient still relied on continuously subcutaneous pump to control blood glucose, pancreatic exocrine function was back to normal, and the development was generally normal. A total of 59 cases were reported in 22 articles, with the case from our hospital, there were 60 patients in total. Among them, 47 were probands and 13 were family members, about 61.7% (29/47) of which were de novo mutations. There were 39 variants, of which 28.2% (11/39) were missense mutations and 71.8% (28/39) were functional deletion variations. Mutations of GATA6 gene had a broad phenotype spectrum. The phenotypes mainly included neonatal diabetes mellitus ( n=39) and pancreatic exocrine insufficiency ( n=39). Other extra-pancreatic features included different types of congenital heart disease ( n=54), congenital biliary abnormalities ( n=23), intestinal developmental disorders ( n=16), neurocognitive disorders ( n=18) and endocrine abnormalities ( n=15). Conclusions:The heterozygous variations of GATA6 gene lead to pancreatic hypoplasia and a broad phenotype spectrum. The pancreatic phenotypes mainly include neonatal diabetes mellitus and pancreatic exocrine insufficiency, and extra-pancreatic phenotypes include congenital heart disease and other developmental abnormalities.

The fall armyworm (FAW), Spodoptera frugiperda, is a destructive pest native to America and has recently become an invasive insect pest in China. Because of its rapid spread and great risks in China, understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies. Here, we assembled a chromosome-level genome of a male FAW (SFynMstLFR) and compared re-sequencing results of the populations from America, Africa, and China. Strain identification of 163 individuals collected from America, Africa and China showed that both C and R strains were found in the American populations, while only C strain was found in the Chinese and African populations. Moreover, population genomics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations. Taken together, FAWs invaded into China were most likely originated from Africa. Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW, of which 283 genes are specific to FAW. Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles, and several detoxification genes such as AOX, UGT and GST specially responded to the pesticides. These findings will be useful in developing effective strategies for management of FAW in China and other invaded areas.
Animals ; China ; Genomics ; Humans ; Male ; Pesticides ; Spodoptera/genetics* ; Transcriptome

【Objective】 To reveal possible mechanisms of miRNA in diabetic hepatopathy through bioinformatics method. 【Methods】 Subset data of miRNA and their matched mRNAs in the liver of STZ-induced diabetic mice and the normal liver tissues of congenial mice by detecting on microarrays were collected from GEO database； information from the database and bioinformatics analysis were applied to mine a batch of miRNAs in diabetic hepatopathy and targeted mRNAs regulated. Then qRT-PCR was used to verify the expressions of miRNAs in diabetic liver from 20 STZ-treated Kunming mice and 10 normal homologous mice. 【Results】 Via detection and analysis， miRNAs differentially expressed （including 96 up-regulated and 77 down-regulated） were significantly obtained. Groups of miRNAs and their effectors （mRNAs） that may be related to the pathological process of diabetic liver disease in mice were screened by GO and KEGG enrichment analyses， combined with relevant protein annotations in the databases and references. The expressions of miR-200a-3p， miR-200b-3p and miR-222-3p in the mice’s liver tissue detected by qRT-PCR were significantly down-regulated. In addition， the expressions of related effector genes CERS6， MYBL1， SCD2， SLCO1A4 and PLK2 were up-regulated， while the expressions of ACSS2， BCL6 and SLC10A2 were down-regulated. 【Conclusion】 The variation trend of those candidate miRNAs in mouse diabetic liver compared with that in control livers was consistent with that of the previous studies and prediction， which revealed their potential molecular regulation in this disease process.

Objectives To review the publications of general practice research in China mainland from 1993 to 2012.Methods The literatures on general practice research published in China mainland from 1993 to 2012 were retrieved from the China Journal Full Text Databases , Wanfang Databases and PubMed . The publications were analyzed using the literature management software NoteExpress 2, Excelland SPSS 19.0.Results A total of 16 349 Chinese publications and 266 English publications of general practice research were collected .The amount of publications was gradually increasing during 1993 and 2012 and there was a sharp increase in the Chinese publications from 2008 to 2012 comparing with the previous years.The Chinese publications in China′s core journals accounted for 32.39%(5 295/16 349) of total of publications;and the English publications in SCI journals accounted for 96.62% ( 257/266 ) of total publications.The authors from community health service facilities accounted for 76.01%(12 427/16 349) of Chinese publications; while authors from research institutes and universities accounted for 61.65%(164/266) of the English publications .Results showed that 37.59% ( 6 145/16 349 ) and 37.12%( 6 069/16 349 ) of the Chinese publications were commentaries and descriptive studies , only 9.57%(1 565/16 349) were randomized controlled trials;52.63% (140/266) of the English publications were descriptive studies and 9.02% ( 24/266 ) were randomized controlled trials .60.75% ( 9 932/16 349 ) of the Chinese publications and 75.94% ( 202/266 ) of the English publications were focused on clinical topics.Conclusion Although the number of general practice publications has been increasing during 1993-2012, the quality of publications is still less satisfactory and need to be further improved .

Objective To investigate the effect of fenofibrate on the matrix metalloprotenase-9 (MMP-9) expression and the proliferation of cultured human umbilical vein endothelial cell (HUVECs) induced by oxidized low density lipoprotein(ox-LDL-C).Methods HUVECs cultured in vitro at passage 4 to 9 were used for the experiment.They were divided into control group,ox-LDL-C group (100 mg/L) and ox-LDL-C + fenofibrate group.The cells in ox-LDL-C + fenofibrate group were firstly incubated with 10,50,100 μmol/L fenofibrate respectively for 6 h,then incubated with 100 mg/L ox-LDL-C for another 24 h.MMP-9 expression in supernatant medium was detected by enzyme-linked immuno sorbent assay (ELISA) and cell proliferation was measured by MTT assay.Results Compared with the control group,ox-LDL-C (100 mg/L) could inhibit the proliferation of HUVECs (P ＜ 0.01) and promote the production of MMP-9 of HUVECs.Fenofibrate could inhibit the proliferation of HUVECs induced by ox-LDL-C in a dose-dependent manner (P ＜ 0.01).Fenofibrate (10,50,100 μmol/L) could significantly stimulate the production of MMP-9 of HUVECs induced by ox-LDL-C (P ＜ 0.01).The stimulation effect was dose-dependent.Conclusion Fenofibrate can inhibit the production of MMP-9 in HUVECs induced by ox-LDL-C,promote the proliferation of HUVECs and protect endothelial function in a dose-dependent manner,then may play the role of anti-artherosclerosis besides lipid regulation.

Objective To investigate the prevalence of vitiligo in China through a multi-center and larse-population epidemiological survey.Methods A community-based survey was conducted in 6 cities from 6 provinces.Cluster sampling method was used.Subjects were required to fulfill the self-report questionnaires and received physical examination by dermatologists.EpiData and SPSS11.5 were utilized for statistical analysis. Results Totally,19 974 patients participated in this study,and 17 345 valid questionnaires were retrieved with a return rate of 86.84%.Of them,122 were found to have vitiligo.The prevalence and standardized prevalence of vitiligo was 0.70% and 0.56% in all patients,0.95% (75) and 0.69% in male patients and 0.50% (47) and O.45% in female patients.respectively.A significant elevation was observed in the prevalence of vitiligo in males than in females (P<0.01).The prevalence of vitiligo was increased with age and peaked in patients aging from 60 to 69 years and those over 70 years.The age at onset of vitiligo varied from 0 to 19 years in 21.85% of these patients,from 20 to 49 years in 47.05%.The most connnon type was focal vitiligo,which accounted for 36.06%,while the rarest type wag segmental type (2.46%).The pesitivity rate of family history of vitiligo was 9.84% in patients and 1.31% in community population (P<0.01).About 31.97% of the patients complained of negative influence of vitiligo on quality of life.Conclusions The standardized prevalence of vitiligo is 0.56%in 6 provinces from China.Males seem to have a higher prevalence of vifiligo than females.

involved,reexamination with colonoscopy is reconanended.