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 role of nitric oxide synthase(NOS)in the regulation of myocardial ischemia-reperfusion(IR)injury in ovariectomized(OVX)rats.Methods A total of 132 female SD rats were subjected,and 48 of them were randomly divided into sham operation group,IR group,OVX group and combined group,with 12 in each group.In order to explore the role of endothelous NOS(eNOS)and inducible NOS(iNOS)in ovariectomization increasing myo-cardial IR injury,another 84 mice were divided into negative sham group,negative IR group,nega-tive combined group,eNOS+IR group,eNOS combined group,iNOS small interfering RNA(si-iNOS)+IR group and si-iNOS combined group,with 12 in each group.The mice of the corre-sponding groups were injected with adeno-associated virus(AAV)overexpressing eNOS or knoc-king down iNOS via tail vein before OVX modeling.Myocardial infarct size,serum levels of lac-tate dehydrogenase(LDH)and creatine phosphokinase isoenzyme(CK-MB),LVEF,LVFS,and expression levels of eNOS and iNOS in the myocardial tissues were measured.Results The com-bined group had significantly increased level of iNOS in myocardium,larger myocardial infarct size and elevated serum LDH and CK-MB levels,but decreased myocardial expression of eNOS and LVEF and LVFS values than the IR group(P＜0.05).When compared with the negative combined group,the myocardial infarct size and serum LDH and CK-MB levels were decreased[(23.51±3.22)％and(26.21±2.93)％vs(58.78±5.42)％,(176.31±15.48 and 169.52±17.12 vs 328.85±37.12 U/L,35.41±6.41 and 34.77±5.94 vs 88.73±9.14 U/L,P＜0.05],and the LVEF and LVFS values were increased[(41.31±3.12)％and(42.09±3.41)％vs(30.77± 2.15)％,(21.47±1.57)％and(21.32±1.42)％vs(15.92±1.33)％,P＜0.05]in the eNOS com-bined group and si-iNOS combined group.Conclusion The decrease of eNOS expression and in-crease of iNOS expression are related to the aggravation of myocardial IR injury in OVX rats.

OBJECTIVE: To retrospectively evaluate the short-term outcomes and safety of computed tomography (CT)-guided percutaneous microwave ablation (MWA) of solitary adrenal metastasis from lung cancer. MATERIALS AND METHODS: From May 2010 to April 2014, 31 patients with unilateral adrenal metastasis from lung cancer who were treated with CT-guided percutaneous MWA were enrolled. This study was conducted with approval from local Institutional Review Board. Clinical outcomes and complications of MWA were assessed. RESULTS: Their tumors ranged from 1.5 to 5.4 cm in diameter. After a median follow-up period of 11.1 months, primary efficacy rate was 90.3% (28/31). Local tumor progression was detected in 7 (22.6%) of 31 cases. Their median overall survival time was 12 months. The 1-year overall survival rate was 44.3%. Median local tumor progression-free survival time was 9 months. Local tumor progression-free survival rate was 77.4%. Of 36 MWA sessions, two (5.6%) had major complications (hypertensive crisis). CONCLUSION: CT-guided percutaneous MWA may be fairly safe and effective for treating solitary adrenal metastasis from lung cancer.
Disease-Free Survival ; Ethics Committees, Research ; Follow-Up Studies ; Humans ; Lung Neoplasms* ; Lung* ; Microwaves* ; Neoplasm Metastasis* ; Retrospective Studies* ; Survival Rate

Objective To study the clinical and genetic features of familial paroxysmal kinesigenic dyskinesia (PKD). Methods The clinical information of 14 family members in one pedigree, including 2 patients (one treated in hos?pital, the other not treated) were analyzed and the response to treatment and prediction were followed up. DNA was ex?tracted from peripheral blood samples, and then screened for PRRT2 mutations. Results There were two male patients in the pure PKD pedigree, Prevalence rate was 14.3%,One of the PKD patients showed good response to carbamazepine as well as lamotrigine whereas other patients recovered without treatment. We detected a nonsense mutation c.797G>A (p.266R>Q) in PRRT2 gene in three family members. One affected member harboring PRRT2 mutation resulted from the incomplete penetrance of the disease,PKD and polycystic kidney disease coexist in the pedigree which showed autoso?mal dominant inheritance with incomplete penetrance and anticipation. Conclusions The curative effect of antiepileptic drugs to purely familial PKD is related to mutations and clinical features;Treatments should be decided based upon clini?cal features and mutations.

Acute Disease ; therapy ; Adult ; Bronchiectasis ; therapy ; Female ; Humans ; Moxibustion

OBJECTIVETo study the expression of cellular inhibitor of apoptosis protein-2 (C-IAP2) mRNA and protein in hepatocellular carcinoma (HCC) and its relationship with the clinical outcomes.

METHODSQuantitative PCR and immunohistochemical staining were used to detect the expression of C-IAP2 mRNA and protein in the tumor tissues and corresponding adjacent non-cancerous tissues from HCC patients.

RESULTSThe expression of C-IAP2 mRNA in HCC tissues was 2.70 folds higher than that in the non-cancerous tissues (P<0.001). The expression rate of C-IAP2 protein in HCC tissues was 70.8%, significantly higher than that in the non-cancerous tissues (27.8%, P=0.001). The expression of C-IAP2 mRNA and protein was associated with the tumor emboli, lymph node metastasis, AFP level, histological differentiation, TNM stage, postoperative recurrence and metastasis (P<0.05), but not with the patients' gender, age, HbsAg positivity, number of tumors, cirrhosis or the presence of tumor encapsulation (P>0.05).

CONCLUSIONThe expression of C-IAP2 in HCC is associated with tumor recurrence and metastasis, and can be a biological marker for prognostic evaluation of HCC.

Baculoviral IAP Repeat-Containing 3 Protein ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Ubiquitin-Protein Ligases

OBJECTIVETo study the expression of special AT-rich sequence binding protein 1 (SATB1) in hepatocellular carcinoma (HCC) cell lines with different invasive capacities.

METHODSSATB1 expression was detected using real-time fluorescence quantitative PCR, RT-PCR, Western blotting and immunofluorescence in immortalized liver cell line HL-7702, noninvasive HCC cell lines HepG2 and SMMC-7721, MHCC97L cells with low invasiveness, and highly invasive cell lines MHCC97H and HCCLM3.

RESULTSIn comparison with HL-7702 cells, all the 5 HCC cell lines showed overexpression of SATB1 mRNA, which was the highest in the highly invasive HCCLM3 and MHCC97H cells, followed by MHCC97L cell line, and then by SMMC-7721 and HepG2 cell lines (P<0.001). The relative expression quantity of SATB1 protein in HepG2, SMMC-7721, MHCC97L, MHCC97H, and HCCLM3 cell lines was 0.271±0.002, 0.351±0.023, 0.621±0.026, 0.878±0.026, and 1.236±0.006, respectively. SATB1 expression level in HCCLM3 cell line was 4.6-fold higher than that in HepG2 cell line (P<0.001). SATB1 was found to localize in the cytoplasm and cell nuclei of the 5 HCC cell lines, and the highly invasive HCCLM3 and MHCC97H cell lines showed a strong positive staining for SATB1 in immunofluorescence assay.

CONCLUSIONSATB1 expression levels differ distinctly between the HCC cell lines with different invasive capacities and are possibly associated with the metastatic potentials of the cells.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Matrix Attachment Region Binding Proteins ; metabolism ; Neoplasm Invasiveness ; RNA, Messenger ; genetics