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 prepare meloxicam solid dispersions tablets, and to investigate their dissolution in vitro. METHODS Crystal inhibition experiments were carried out to screen the carrier materials, and the solid dispersion was characterized by X-ray diffraction(XRD) amd differential scanning calorimeter(DCS). The improved bioavailability of solid dispersions was evaluated through in vivo pharmacokinetic studies. The optimum preparation process of meloxicam solid dispersion tablets was investigated, and the in vitro dissolution curve similarity factor f2 was used as the main evaluation index to screen and optimize the dosage of pH regulator, filler, disintegrator, lubricant, flow aid and the mixing time in the prescription. RESULTS The solid dispersion prepared with Kollidon@VA64 as carrier effectively maintained the supersaturated state of the drug in solution. The results of XRD and DSC showed that the crystal state of meloxicam in the solid dispersion was completely transformed into amorphous state. Compared with meloxicam, solid dispersions significantly increased the solubility, and its peak blood concentration(Cmax) and relative bioavailability were increased by 208.09% and 241.78%, respectively. The optimal formulation and process of meloxicam solid dispersion tablets prepared by direct powder pressing method were meloxicam solid dispersion 35.2%, lactose∶microcrystalline cellulose =1∶1.5, sodium citrate 9.8%, crosslinked povidone 8%, magnesium stearate 0.75%, silica 0.8%, and mixing time 5 min. The dissolution similarity factor f2 of the prepared meloxicam solid dispersion tablets and the original reference preparation in different pH medium was above 50. CONCLUSION Meloxicam solid dispersible tablets are prepared by hot melt extrusion and powder pressing method. The dissolution and bioavailability of meloxicam are improved, and the dissolution behavior of meloxicam is similar to that of the original reference preparation.

To better promote the development of film-coated formulations and membrane agents, the present study was carried out to investigate the critical material attributes (CMAs) of different sources and models of HPMC in terms of film-coating performance and the correlation between each of the CMAs and the film-coating-related properties, using 2910 HPMC as the research target. Firstly, various analytical techniques were used to characterize the CMAs and film coating-related properties of HPMC. Secondly, the CMAs and film coating-related properties of HPMC were systematically evaluated by principal component analysis (PCA) and orthogonal partial least-squares discrimination analysis (OPLS-DA). The CMAs and film-coating-related properties of HPMC were systematically evaluated to elucidate the intrinsic relationship between the CMAs and film-coating-related properties of HPMC. The results showed that there were significant differences in viscosity, weight-average molecular weight, film tensile strength, elongation, elastic modulus, dissolution time, and flexibility of HPMCs from different manufacturers. The results of PCA and OPLS-DA analyses indicated that these 11 variables showed some correlations with each other. Both mathematical models showed better differentiation and classification of HPMC samples, and the OPLS-DA model had a better classification effect than the PCA model. Therefore, in this study, the physicochemical properties and the film-forming characteristic of HPMC were comprehensively evaluated, and the correlation between them was further established using PCA and OPLS-DA. The impact degree of different CMAs on the film coating performance of HPMC was clarified, which can be used as an important reference for the selection of excipient quality control programs in excipient production and formulation research and development.

AIM: To simutaneously determinate the four components of dipyridamole, quercetin,kaempferol and isorhamnetin in Ginkgo-Leaf-Extract Dipyridamole Injection by the reversed-phase high performance liquid chromatographic (RP-HPLC). METHODS: Ginkgo-Leaf-Extract Dipyridamole Injection was determined by RP-HPLC on Scienhome Kromasil C_ 18 (250 mm? 4.6 mm, 5 ?m) column. The mobile phase consisted of methanol and 0.4% phosphoric acid solution (55∶ 45, v/v), the flow rate of 0.80 mL/min and UV detection wavelength at 360 nm were set to determine the contents of the four components. RESULTS: There were good linear relationships between peak area and concentration of the four components, and the calibration curves were linear in the ranges of 21.7 -261.0 ?g/mL for dipyridamole, 8.0 -96.0 ?g/mL for quercetin, 7.75 -93.0 ?g/mL for kaempferol, 5.75 -69.0 ?g/mL for isorhamnetin. The precisions for dipyridamole, quercetin, kaempferol and isorhamnetin were 1.16% , 1.35% , 1.21% and 1.58% , respectively. The average recoveries were 100.3% , 100.0% , 99.86% and 99.80% , respectively. CONCLUSION: The four components of the dipyridamole, quercetin, kaempferol and isorhamnetin in Ginkgo-Left-Extract Dipyridamole Injection are determined at the same time, and the method is simple, sensitive and accurate.

AIM:To establish the assessing method of traditional Chinese medicine chromatogrphic fingerprints by the involution similarity and quantitative involution similarity and its application. METHODS: The fingerprint of Ginkgo biloba L.extract(GBE) was evaluated by the involution similarity and quantitative involution similarity,and the contrast studies were implemented by other appraisal targets,eg.the included angle cosine S_F,the correlation coefficient r and the indexes with quantitative characteristic,such as the apparently quantitative similarity R%、the average mass percent M%,etc.. RESULTS: The involution similarity could reflect the similarity change in each sample from different bathes and be of quantitative function.The quantitative involution similarity and quantitative weighted similarity could perfectly reflect the changes in contents of the consituents of GBE. CONCLUSION: The involution similarity and quantitative involution similarity can qualitatively and quantitatively assess the similarity between sample and the referential fingerprint.They are certainly the novel method of evaluating the traditional Chinese medicine chromatographic fingerprints.