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.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective To analyze the influencing factors of survival of patients with airway stenosis requiring clinical interventions after lung transplantation. Methods Clinical data of 66 patients with airway stenosis requiring clinical interventions after lung transplantation were retrospectively analyzed. Univariate and multivariate Cox’s regression models were adopted to analyze the influencing factors of survival of all patients with airway stenosis and those with early airway stenosis. Kaplan-Meier method was used to calculate the overall survival and delineate the survival curve. Results For 66 patients with airway stenosis, the median airway stenosis-free time was 72 (52,102) d, 27% (18/66) for central airway stenosis and 73% (48/66) for distal airway stenosis. Postoperative mechanical ventilation time [hazard ratio (HR) 1.037, 95% confidence interval (CI) 1.005-1.070, P=0.024] and type of surgery (HR 0.400, 95%CI 0.177-0.903, P=0.027) were correlated with the survival of patients with airway stenosis after lung transplantation. The longer the postoperative mechanical ventilation time, the higher the risk of mortality of the recipients. The overall survival of airway stenosis recipients undergoing bilateral lung transplantation was better than that of their counterparts after single lung transplantation. Subgroup analysis showed that grade 3 primary graft dysfunction (PGD) (HR 4.577, 95%CI 1.439-14.555, P=0.010) and immunosuppressive drugs (HR 0.079, 95%CI 0.022-0.287, P<0.001) were associated with the survival of patients with early airway stenosis after lung transplantation. The overall survival of patients with early airway stenosis after lung transplantation without grade 3 PGD was better compared with that of those with grade 3 PGD. The overall survival of patients with early airway stenosis after lung transplantation treated with tacrolimus was superior to that of their counterparts treated with cyclosporine. Conclusions Long postoperative mechanical ventilation time, single lung transplantation, grade 3 PGD and use of cyclosporine may affect the survival of patients with airway stenosis after lung transplantation.

Objectives:Primary cardiac involvement (SSc-PHI) in systemic sclerosis is an important prognostic factor. We aimed to characterize and identify subclinical SSc-PHI using cardiovascular MRI to determine whether disease severity and serum biomarkers are associated with subclinical SSc-PHI.Methods:A total of 26 patients with SSc who had no history of cardiovascular disease or pulmonary hypertension underwent 3 T-enhanced cardiovascular MRI. Measurements included native T 1, extracellular volume, advanced gadolinium enhancement, T 2 mapping, and left ventricular volume function. Troponin T and N telencephalic natriuretic peptide precursors were also determined. Results:LGE was observed in 13 of 26 patients (50.0%), suggesting focal fibrosis, and T 2 mapping was significantly higher in the dcSSc group than in the lcSSc group ( P=0.009). Left ventricular volume and function were within the normal range in all patients, but final systolic left ventricular volume was significantly higher in dcSSc than in lcSSc ( P=0.021). The modified Rodnan skin score (mRSS) was significantly higher in patients with LGE focal fibrosis ( P=0.019). Logistic regression analysis confirmed the association between mRSS and LGE ( OR=1.224, P=0.037). In multivariate analysis, T 2 mapping was negatively correlated with disease course, and was correlated with dcSSc and fingertip ulcer ( R2=0.711, P=0.018, P=0.013, P=0.030). Troponin T was correlated with T 2 mapping ( r=0.555, P=0.049). Conclusions:Subclinical SSc-PHI is characterized by diffuse and focal myocardial fibrosis, but preserves myocardial systolic function. Subclinical SSC-Phi is associated with TNT, SSc disease severity, and complex peripheral vascular disease. These data provide information for identifying individuals at risk of SSc-PHI.

The phenomenon of coronary artery ectasia is typically discovered incidentally during coronary angiography.As a relatively uncommon manifestation of coronary arteries,it has attracted the interest of numerous researchers.However,despite extensive research on coronary artery ectasia,substantial controversies persist regarding both its etiology and treatment modalities.This article provides a comprehensive summary of recent research on coronary artery ectasia,elucidates various aspects of research progress,with the aim of offering substantive support and guidance for subsequent investigations.

As the final resolution for end-stage lung disease, lung transplantation can not only significantly prolong the survival, but also remarkably improve the quality of life of recipients. In recent decades, with the advancement of surgical techniques, immunosuppressants and post-transplantation management, the quantity of lung transplantation has been surged around the globe. However, the shortage of donor lung has severely restricted the development of lung transplantation. It is necessary to develop innovative approaches to expand the donor pool. The number of donors and effective preservation and functional maintenance of potential donor lungs play a key role in expanding the donor pool. The quality of donor lung is a critical precondition to ensure the long-term survival of lung transplant recipients. Preservation and functional maintenance of donor lung are of significance for guaranteeing the quality of lung allograft. In this article, research progresses on the management and maintenance of donor lung before procurement, the procurement of donor lung and the preservation and functional maintenance of lung allograft were reviewed, aiming to provide reference for the development of lung transplantation in clinical practice.

AIM: To investigate the effect of autophagy on cell ferroptosis in intestinal ischemia-reperfusion injury. METHODS: Twenty-four SPF grade Wistar rats weighing 200-220 g were divided into 4 groups (n = 6): sham operation group (sham group), ischemia group (I group), ischemia-reperfusion group (I/R group),and ischemia-reperfusion + autophagy inhibitor group (I/R + 3-MA group). The ischemia model was established by clamping the superior mesenteric artery for 1 hour, and the intestinal ischemia-reperfusion injury model was established by reperfusion for 2 hours. HE staining was used to observe the pathological changes of intestinal mucosa and Chiu score under light microscope. Fe

Objective:To provide consistent data basis for the application of reference intervals for children blood cell analysis in different testing systems.Methods:According to the requirements of American Institute for Clinical and Laboratory Standardization (CLSI) EP9-A3 document, 45 samples were collected and Sysmex XN20-A1 were used as reference system. Beckman DxH800, Siemens ADVIA 2120i, and Mindray BC5310 were comparison systems. Complete blood count and leukocyte classification were performed by four systems. The outliers of the detection results were tested by the generalized extreme student deviate (ESD) method. An optimal regression model was selected by scatter diagram, deviation diagram and frequency distribution diagram, which was used to fit the regression equation and calculate the deviation at the medical decision level and reference interval. The acceptable range for blood count deviation was cited from the Analytical Quality Specifications for Routine Tests in Clinical Hematology. The acceptable range for leukocyte classification was based on the EQA program of Royal College of Pathologists of Australasia (RCPA).Results:After the outliers were deleted, the scatter plot showed a linear relationship between the reference system and the three comparison systems. The deviation plot showed that the differences were variable. Deming regression or Passing-Bablok regression was selected according to the data distribution. The determination coefficient R2 of reference system and three comparison systems ranged from 0.95 to 0.99 in blood count and leukocyte classification. At the upper and lower limits of the reference interval, the deviations between XN-20A1 and ADVIA 2120 system were all acceptable, except for MONO# at 0.12×10 9/L. The deviations of all parameters at medical decision level were within acceptable ranges. The lower limit of PLT is partially unacceptable at the level of medical decision related to treatment and prognosis. Conclusions:The results of complete blood count and leukocyte classification in reference system and the comparison system had good consistency within the children′s reference interval. Our study provided a scientific basis for the feasibility of adopting a unified reference interval for different detection systems.

Alphapapillomavirus ; Humans ; Lupus Erythematosus, Systemic ; Papillomavirus Infections/prevention & control* ; Vaccination

Bone defects caused by trauma, infection, tumor and other factors is a thorny problem in orthopedic clinic, and promoting bone repair and regeneration is the key and difficult point of treatment. In addition to autologous bone grafting, artificial bone materials are often used for large bone defects. β-tricalcium phosphate has good biocompatibility, bone conduction and bone induction properties, and has been studied deeply because of its excellent drug delivery performance and has shown broad application prospects. In this paper, the author will summarize the research progress of β-tricalcium phosphate composites loaded with different drugs in the treatment of bone defects caused by trauma, infection and tumor.