HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To establish a carbohydrate metabolism-related genes(CRGs)prognostic model for clear cell renal cell carcinoma(ccRCC)and investigate its clinical value.Methods:ccRCC mRNA expression data were sourced from The Cancer Genome Atlas(TCGA)data-base.CRGs were retrieved from the MSigDB and KEGG databases.A prognostic model based on CRGs was constructed using the LASSO lin-ear regression model,and the risk score(RS)was calculated.Patients were assigned into high-and low-risk groups according to the median RS.Differences in survival,immune infiltration,mutation,and immune response between the two groups were analyzed using Kaplan-Meier curves and bioinformatics methods.Constructing a nomogram based on the RS and clinical features and validating its accuracy of prognostic predictions.The expression of CRGs in the ccRCC samples was detected using RT-qPCR.Results:A total of eight key genes were utilized to construct a prognostic risk model for ccRCC.Survival analysis revealed that patients in the low-risk group had a better prognosis(P<0.001).Bioinformatics analysis showed that the RS correlated with immune cell infiltration,mutation,and immune responses.The nomogram based on the RS and clinical features demonstrated a strong predictive ability for prognosis.In vitro experiments confirmed notable differences in the expression of the eight CRGs between ccRCC and adjacent non-malignant tissues.Conclusions:A prognostic model based on CRGs can effectively predict the prognosis of patients with ccRCC.

OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model， using accumulative absorption amount （Q） and absorption rate constant （Ka） as indexes， UHPLC-MS/MS technique as a method， the absorption of saikosaponin A， B2， C， D and F from total saponins of Bupleurum chinense （8 g/mL， by crude drug） in the duodenum， jejunum and ileum was detected. RESULTS The correlation coefficients （r） of the regression equations for the absorption of saikosaponins A， B2， C and F in the duodenum， jejunum and ileum were all higher than 0.95， while the r of saikosaponin D in the above intestinal segments was lower than 0.95； compared with the absorption of the same composition in the duodenum， the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min， as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased （P＜0.05）. CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum， jejunum and ileum； among them， saikosaponin A， B2， C and F are linearly absorbed， which conforms to the zero-order absorption characteristics， but saikosaponin D shows non- linear absorption.

Objective To evaluate the manifestations and diagnostic value of CT enterography (CTE) in primary intestinal T-cell lymphoma (PITCL).Methods Eighteen patients with PITCL confirmed by pathology were reviewed retrospec tively.The characteristics of lesion site,amount of foci,pattern and degree of contrast enhancement,lymphadenopathy,involvement of other organs and complications were recorded.Results In all of the 18 patients with PITCL,multiple lesions were seen in 13 cases (13/18,72.22％),and solitary involvement was seen in 5 cases (5/18,27.78％).Twelve ca ses were located at jejunum/ileum,3 of them were also involved in the colon.Five cases were located only in the colon,and 1 in the duodenum.Six cases were complicated with intestinal perforation.The patients were categorized into 6 types according to the CT manifestation:infiltration type (n=7),diffuse jejunum mucosa ileum metaplasia type (n =3),luminal aneurismal dilatation type (n =3),polypoid mass type (n =2),mesentery type (n=1),mixed type (n =2).Conclusion CTE can clearly display the imaging of PITCL and it has high value for the diagnosis of PITCL.

BACKGROUND:Our previous studies have shown that a soft substrate has a significant effect on morphology and cytoskeleton of rat bone marrow mesenchymal stem cel.
OBJECTIVE:To explore the effect of polyacrylamide gels as soft substrates with different elastic moduli on the chondrogenic differentiation of human synovial-derived mesenchymal stem cels.
METHODS:The synovium was harvested from patients with osteoarthritis under sterile conditions, and primary human synovial-derived mesenchymal stem cels were separated using limiting dilution assay. The flow cytometry and multi-directional differentiation experiments were used to identify the cel surface markers and function of the human synovial-derived mesenchymal stem cels, respectively. The polyacrylamide gels with the elastic modulus of 0.4, 6, 30 kPa, which were made using various amounts of acrylamide and bis-acrylamide, were used to culture human synovial-derived mesenchymal stem cels under induction with transforming growth factor-β1 for 7 and 14 days. RT-PCR was used to test the expression of chondrogenic genes, type II colagen gene and cartilage acidic protein 1. The 6-wel cel culture plates served as controls.
RESULTS AND CONCLUSION: The human synovial-derived mesenchymal stem cels showed different cel morphology in the different elastic modulus of polyacrylamide gels. The expression of type II colagen gene and cartilage acidic protein 1 were affected by the different elastic modulus of polyacrylamide gels and culture time, and there was an interaction between these two factors. At 7 days of induction, the expression of cartilage acidic protein 1 gene on 6 kPa polyacrylamide gels was the highest (F=44.350,P=0.000); meanwhile, the expression of type II colagen gene on 0.4 kPa polyacrylamide gels was the highest (F=6.384,P=0.005). These findings indicate that polyacrylamide gels with lower elastic modulus are superior to routine culture plates to promote the chondrogenic differentiation of human synovial-derived mesenchymal stem cels.