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 explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties. METHODS: Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized. RESULTS: SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets. CONCLUSION The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.
Drug Liberation ; Excipients ; Printing, Three-Dimensional ; Reproducibility of Results ; Tablets

OBJECTIVETo evaluate clinical results of an interspinous stabilization system (Wallis) in treating lumbar degenerative disease in the short-term.

METHODSFrom August 2007 to June 2010,48 patients with lumbar degenerative disease who were treated with interspinous stabilization system, the data of patients were analyzed retrospectively. In all of the 48 cases, there were 30 males and 18 females with an average age of 54.2 years (ranged, 40 to 68 years). Forty-four cases were with single segment and 4 cases with two segments. Of them, 4 cases were in L3, 4, 40 cases were in L4, 5, 4 cases were in L3, 4 and L4, 5. The radiographic data of patients were analyzed. Clinical effects were evaluated by Japanese Orthopedic Association (JOA) score system and low back pain disability questionnaire (Oswestry) and Odom method.

RESULTSAll the patients were followed up from 1 to 2 years with an average of 18 months. According to Odom's criteria, 20 cases obtained excellent results, 24 good, 4 fair. JOA score increased from 12.4 +/- 2.7 preoperatively to 26.1 +/- 2.0 postoperatively (P < 0.01). Oswestry score decreased from 14.1 +/- 2.9 preoperatively to 5.5 +/- 1.8 postoperatively (P < 0.01). The posterior height of intervertebral space and height of nerve root canal increased compared with that of preperative height.

CONCLUSIONThe treatment of lumbar degenerative disease with interspinous stabilization system can obtain satisfactory effects in the near future. It can retain dynamic stable of corresponding segments, expand volume of vertebral canal, and is safe and feasible.

Adult ; Aged ; Female ; Humans ; Intervertebral Disc Degeneration ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Spinal Stenosis ; surgery

BACKGROUNDUnderstanding the characteristics of Chinese dialysis patients and the current practice trends is the first step to evaluate the association between practice pattern and outcome in these populations. In the present study, we evaluated the status of medical treatment and characteristic features of chronic dialysis patients in China.

METHODSThrough a clustering sampling, we selected 9 centers from the largest dialysis facilities in 6 cities around China. All adult undergoing dialysis in the selected units were screened. A total of 2388 (1775 on hemodialysis (HD) and 613 on peritoneal dialysis (PD)) patients were finally enrolled. All data were collected at enrollment on the bases of review of medical records.

RESULTSIn this cohort, 1313 (55.0%) were male. The mean age was 54 years old. The median time for dialysis was 26 months (12 - 51 months). Seventy-five percent of patients were on HD and 25.0% on PD. Among PD patients, about 21% patients did not receive dialysis adequacy. For HD patients, about 14.0% of them did not achieve dialysis adequacy when the target of kt/V was set as 1.2. Only 44.7% of patients achieved blood pressure target of 140/90 mmHg. About 60% of patients did not reach the hemoglobin target of 110 g/L even though 85.0% of them were treated with erythropoietin. In addition, 48.5% of the patients had uncontrolled mineral metabolism revealed by the high calcium-phosphate product. Compared with HD patients, higher level of serum glucose, triglyceride, and total and low density lipoprotein cholesterol were more common in PD patients.

CONCLUSIONSThis observational study suggests that many Chinese dialysis patients did not achieve the therapeutic target, particularly in blood pressure control, anemia correction, and mineral balance. PD patients were more likely to suffer metabolic disturbance.

Adult ; Aged ; Anemia ; physiopathology ; Blood Pressure ; physiology ; Female ; Humans ; Male ; Middle Aged ; Peritoneal Dialysis ; Renal Dialysis

To investigate the Fe2+ effects on root tips in rice plant, experiments were carried out using border cells in vitro. The border cells were pre-planted in aeroponic culture and detached from root tips. Most border cells have a long elliptical shape. The number and the viability of border cells in situ reached the maxima of 1600 and 97.5%, respectively, at 20-25 mm root length. This mortality was more pronounced at the first 1-12 h exposure to 250 mg/L Fe2+ than at the last 12-36 h. After 36 h, the cell viability exposed to 250 mg/L Fe2+ decreased to nought, whereas it was 46.5% at 0 mg/L Fe2+. Increased Fe2+ dosage stimulated the death of detached border cells from rice cultivars. After 4 h Fe2+ treatment, the cell viabilities were > or =80% at 0 and 50 mg/L Fe2+ treatment and were <62% at 150, 250 and 350 mg/L Fe2+ treatment; The viability of border cells decreased by 10% when the Fe2+ concentration increased by 100 mg/L. After 24 h Fe2+ treatment, the viabilities of border cells at all the Fe2+ levels were <65%; The viability of border cells decreased by 20% when the Fe2+ concentration increased by 100 mg/L. The decreased viabilities of border cells indicated that Fe2+ dosage and treatment time would cause deadly effect on the border cells. The increased cell death could protect the root tips from toxic harm. Therefore, it may protect root from the damage caused by harmful iron toxicity.
Iron ; toxicity ; Oryza ; cytology ; drug effects ; growth & development ; Plant Roots ; cytology ; drug effects ; growth & development ; Seedlings ; cytology ; drug effects ; growth & development

2',5'-Oligoadenylate Synthetase ; genetics ; Adult ; Carrier State ; virology ; Case-Control Studies ; Female ; Hepatitis B ; drug therapy ; genetics ; virology ; Hepatitis B virus ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Polymorphism, Genetic ; Recombinant Proteins

Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins