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 investigate the effect of iron deficiency on the prognosis of elderly patients with ejection fraction preserved heart failure (HFpEF).Methods:The clinical data of old patients (>75 years) with HFpEF from November 2021 to May 2023 in General Hospital of Eastern Theater of the Chinese People′s Liberation Army were retrospectively analyzed. The patients were divided into iron deficiency group (65 cases) and non-iron deficiency group (90 cases) according to serum ferritin (SF) and transferrin saturation (TSAT) at admission. The first hematological indexes and echocardiogram examination results after admission were compared between two groups. The patients were followed up until November 2023, the poor prognosis was recorded. The correlation between iron deficiency, iron metabolism indexes and poor prognosis in elderly patients with HFpEF was analyzed by Spearman correlation analysis. The Kaplan-Meier survival curve was drawn to analyze the effect of iron deficiency on the cumulative survival in elderly patients with HFpEF.Results:There were no statistical difference in triglyceride, total cholesterol, low density lipoprotein cholesterol, C-reactive protein, hemoglobin and echocardiogram indexes between the two groups ( P>0.05). The N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine, procalcitonin (PCT) and interleukin-6 (IL-6) in iron deficiency group were significantly higher than those in non-iron deficiency group: 427.23 (281.00, 736.90) pmol/L vs. 313.50 (182.47, 363.25) pmol/L, (167.93 ± 51.22) μmol/L vs. (121.71 ± 11.99) μmol/L, 0.12 (0.05, 0.22) μg/L vs. 0.07 (0.04, 0.16) μg/L and 25.60 (8.38, 47.01) ng/L vs. 10.15 (4.75, 19.89) ng/L, the SF, serum iron (SI) and TSAT were significantly lower than those in non-iron deficiency group: 75.40 (42.30, 198.00) μg/L vs. 207.00 (281.00, 736.90) μg/L, (6.49 ± 2.66) μmol/L vs. (12.75 ± 4.24) μmol/L and (16.65 ± 6.26)% vs. (33.78 ± 11.16)%, and there were statistical differences ( P<0.01 or <0.05). The patients were followed up for (12.06 ± 7.58) months, the all-cause mortality, cardiovascular mortality, readmission rate and heart failure readmission rate in iron deficiency group were significantly higher than those in non-iron deficiency group: 40.0% (26/65) vs. 20.0% (18/90), 18.5% (12/65) vs. 4.4% (4/90), 90.8% (59/65) vs. 70.0% (63/90) and 66.2% (43/65) vs. 17.8% (16/90), and there were statistical differences ( P<0.01). Spearman correlation analysis result showed that the iron deficiency was positive correlation with all-cause death, cardiovascular death, readmission and heart failure readmission in elderly patients with HFpEF ( P<0.01); the SI and TSAT were negative correlation with all-cause death, cardiovascular death, readmission and heart failure readmission ( P<0.01 or <0.05); and the SF was not correlation with the indexes ( P>0.05). Kaplan-Meier survival analysis result showed that the risk of all-cause death was significantly increased in elderly HFpEF patients with iron deficiency, and the cumulative survival rate was significantly reduced (log-rank χ2 = 6.48, P<0.05). Conclusions:The elderly HFpEF patients with iron deficiency have poor prognosis with high mortality and readmission rate.

Objective:To investigate the relation between 25 hydroxyvitamin D3 level and global registry of acute coronary event (GRACE) score in elderly patients with acute coronary syndrome (ACS).Methods:The clinical data of 120 elderly male patients with ACS hospitalized in the General Hospital of Eastern Theater Command from January 2020 to June 2022 were retrospectively analyzed. Clinical characteristics of patients were collected and the 25 hydroxyvitamin D3 level was assessed with the chemiluminescent immunoassay method. According to GRACE score, the patients were divided into intermediate-risk group (109 to 140 scores, 46 cases) and high-risk group(>140 scores, 74 cases). The severity of coronary lesion was assessed according to the results of coronary angiography (CAG) and then they were divided into A, B, C group. The independent influential factors of GRACE score were analyzed by Logistic regression analysis.Results:The level of 25 hydroxyvitamin D3 in the high-risk group was lower than that in the intermediate-risk group: (13.84 ± 3.42) μg/L vs. (18.57 ± 5.17) μg/L, the usage rate of angiotensin-converting enzyme inhibitors (ACEI)/angiotonin receptor blocker (ARB) in the high-risk group was lower than that in the intermediate-risk group: 17.6%(13/71) vs. 41.3%(19/46), there were statistical differences ( P<0.05). Logistic regression analysis showed that 25 hydroxyvitamin D3 level was the risk factor for GRACE score ( OR = 0.745, 95% CI 0.657-0.844, P<0.05). The level of 25 hydroxyvitamin D3 had negative correlation with the severity of coronary lesion ( P<0.05). Conclusions:The level of 25 hydroxyvitamin D3 has correlation with GRACE score and the severity of coronary lesion in elderly patients with ACS.

This paper aims to discuss the ideas and experience about the radiology residency training system of Canada with a presentation of its base accreditation standards for five aspects, competency goals for seven roles, four stages of training arrangement, and two types of final assessment questions. Although the Canada's radiology residency program differs from China's standardized resident and specialist training programs for radiology, there are still several points that are worth referencing, including emphasizing the training priority of competency goals, providing a specific basis for the stratification of training, offering clear guidance for the implementation of training content, and improving assessment methods to focus on competency goals. These points are of great value for improving the standardized radiology resident and specialist training programs in China, so as to provide a reference for the training of excellent radiologists in China.

The teaching of radiology in standardized residency training needs a large number of case data to strengthen the subjective understanding and awareness of residents. The database built by residency training bases can meet the needs of teaching to a certain extent, but the conditions of training bases vary across regions, which makes it difficult to achieve homogeneity in the teaching of radiology. This article discusses the application of Eurorad database in the teaching of radiology in standardized residency training. This database is free of charge, reliable, and comprehensive and provides a large number of free reliable cases and images for teaching, covering both common and rare diseases. Moreover, it can also be used to cultivate the English ability and comprehensive quality of residents and help to establish a hierarchical training system for radiology and non-radiology residents, thereby promoting the improvement in the quality of standardized residency training. This article shows the potential value of Eurorad database in the teaching of radiology in standardized residency training, and comparative studies are needed in the future to further prove its effectiveness.

【Objective】 To investigate the effect of total flavone of oldenlandia diffusa(FOD) on the stemness, proliferation and apoptosis of breast cancer(BC) stem cells sorted from MDA-MB-231. 【Methods】 Human BC cell lines MDA-MB-231 was cultured in vitro; MDA-MB-231 was stimulated by different concentrations(0 μg/mL, 100 μg/mL, 200 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h and 72 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on MDA-MB-231 proliferation; CD44⁺/CD24^-MDA-MB-231 cell line were tested by flow cytometry and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting; Annexin V-PE/7-AAD was used to detect the effect of FOD on MDA-MB-231 apoptosis and Bcl2, cleaved-caspase3 and Bax were tested by Western blotting. 【Results】 Cell proliferation of MDA-MB-231 was significantly inhibited by FOD, with the significant suppression at concentrations of 400 μg/mL for 72 h compared with negative control group(P<0.05). The apoptosis rate was significantly upregulated than the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and cleaved-caspae3 increased, and stemness markers such as Nanog, Sox2 and Oct4 decreased in FOD-treated cells. Moverover, Akt-GSK3β-β-catenin axis was inhibited in FOD-treated cells. 【Conclusion】 FOD could significantly inhibit the stemness and proliferation and promote the apoptosis of MDA-MB-231.

Objective:To investigate the clinical application of the free medial plantar artery perforator flap for soft tissue defect reconstruction of the weight-bearing surface of the heel.Methods:The clinical data of patients with soft tissue defects in the weight-bearing surface of the heel were analyzed retrospectively, which were reconstructed with the free medial plantar artery perforator flaps in the Second Hospital of Tangshan from April 2011 to November 2017. The medial plantar artery was anastomosed with the posterior tibial artery. The venae comitantes were anastomosed with the great saphenous vein. The cutaneous branch of the medial plantar nerve was also anastomosed with the saphenous nerve. The donor sites were covered with full-thickness skin grafting. The survival condition, sensory function, countour, stability, and donor site scars were observed during follow-up.Results:A total of 11 patients with soft tissue defects in the weight-bearing surface of the heel were enrolled. There were six males and five females aged 24-41 years (mean, 31.3 years). All flaps survived uneventfully. Patients were followed up 11-56 months (mean 18.5 months). The appearance and function recovery of the flaps were satisfactory with 6-13 mm two-point discrimination(2-PD). No ulcer occurred. All patients returned to a normal walk.Conclusions:It is a feasible way for one-staged reconstruction of the combined loss of Achilles tendon and soft tissue in the heel by using free anterolateral femoral artery perforator flap with fascia lata, which has the advantages of good functional recovery, less trauma, short curing course, the satisfactory contour, and protective sensation achievable.

Objective:To investigate the clinical application of the free medial plantar artery perforator flap for soft tissue defect reconstruction of the weight-bearing surface of the heel.Methods:The clinical data of patients with soft tissue defects in the weight-bearing surface of the heel were analyzed retrospectively, which were reconstructed with the free medial plantar artery perforator flaps in the Second Hospital of Tangshan from April 2011 to November 2017. The medial plantar artery was anastomosed with the posterior tibial artery. The venae comitantes were anastomosed with the great saphenous vein. The cutaneous branch of the medial plantar nerve was also anastomosed with the saphenous nerve. The donor sites were covered with full-thickness skin grafting. The survival condition, sensory function, countour, stability, and donor site scars were observed during follow-up.Results:A total of 11 patients with soft tissue defects in the weight-bearing surface of the heel were enrolled. There were six males and five females aged 24-41 years (mean, 31.3 years). All flaps survived uneventfully. Patients were followed up 11-56 months (mean 18.5 months). The appearance and function recovery of the flaps were satisfactory with 6-13 mm two-point discrimination(2-PD). No ulcer occurred. All patients returned to a normal walk.Conclusions:It is a feasible way for one-staged reconstruction of the combined loss of Achilles tendon and soft tissue in the heel by using free anterolateral femoral artery perforator flap with fascia lata, which has the advantages of good functional recovery, less trauma, short curing course, the satisfactory contour, and protective sensation achievable.

Osteosarcoma is a highly malignant bone tumor that predominantly affects children and adolescents. Standard chemotherapy currently used is usually poor, with a lower survival rate of patients with recurrence or metastasis. And it is necessary to find precise targeted therapy drugs from a genic perspective. This paper reviews the progress of genome research on germline mutation and somatic mutation of osteosarcoma in recent years, summarizes mutations and pathways that are closely related to osteosarcoma and can reflect the characteristics of osteosarcoma in order to provide a hope for the next generation of molecular targeted therapy.

Isolation and characterization of metabolites produced by endophytes are significant ways to search for novel natural active substances, proving that the endophytes are the unique resources of newer and more effective compounds. Many new compounds with antimicrobial activity from different endophytes have been isolated so far. These new compounds provide alternatives to fight against multi-drug resistance of microorganisms. This review outlined the major achievements and latest developments of endophytes, including the diversity of endophytes and antimicrobial activity of endophytes, as well as its development in China.