Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

Objective To retrospectively analyze the engraftment, transplant-related complications and survival after unrelated cord blood transplantation (UCBT) in patients with hematologic malignancies. Methods Fifty consecutive patients with hematological malignancies (median age, 19 years; median weight, 53 kg) were treated with UCBT in single center from April 2000 to August 2009. Thirty-nine patients were high-risk or refractory. Double UCB grafts were used for 26 patients, while single UCB graft for 24 patients. Myeloablative conditioning was given to 45 cases and non-myeloablative regimens to 5 cases. All patients were given a combination of cyclosporin A (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. Results The median total nucleated cell (TNC) dose was 4.0 (range, 1.95-16.24)×10~7 TNC/ kginfused, and CD34~+ cell dose was 2.74(range, 0.67-29.28)×10~5/kginfused. Forty-two of 50 patients acquired engraftment with implantation rate being 86%. The median time to engraftment (absolute neutrophil count>500/mm~3 and platelets 20 000/L) was 19 and 34 days. The cumulative incidence of neutrophil engraftment by day 42 was 86.3%(95% confidence interval [CI] 0.769-0.957); the cumulative incidence of platelets engraftment by day 120 was 72.3% (95% CI 0.620-0.821). Twenty cases developed acute GVHD, and the incidence of acute GVHD of grades Ⅲ/Ⅳ by day 100 was 7.1%. The incidence of chronic GVHD within 2 years was 17.4%. During a median follow-up period of 22 months (range 4-116), Overall 6-month, 1-year and 2-year survival rate was 66.2%(95% CI 0.590-0.734), 57.4%(95% CI 0.496-0.652), 54.2%(95% CI 0.462-0.622), respectively. For the patients with non-advanced hemotologic malignancies, 6-month, 1-year and 2-year survival rate was 73.2% (95% CI 0.659-0.805), 66.1% (95% CI 0.579-0.743), and 62.2% (95% CI 0.542-0.682) respectively. Five cases relapsed. The cumulative incidence of relapse within 2 years was 16.2% (95% CI 0.099-0.225). Twenty-one cases died mainly due to infection. Conclusion UCBT could be safely and effectively used for adult patients with hematologic malignancies.

Objective To investigate the treatment effect of proximal femoral nail antirotation (PFNA) on unstable femoral intertrochanterie fractures in the elderly. Methods A retrospective stud- y was done on 65 patients with unstable femoral intertrochanteric fractures, who were treated with PFNA from December 2005 to October 2006 and followed up for at least half a year. There were 22 males and 43 females, at age range of 67-97 (mean 78.5 years). All the operations were carried out within a week af- ter fractures. The data of operation time, operative blood loss, complications, bone healing time and hip function scores were recorded for evaluating treatment outcomes. Results All the patients were fol- lowed up for 6-18 months (average 10.5 months). The operation lasted for (29.6±7.5) minutes, with mean blood loss of (150.5±40.2) ml and bone healing time of (9.1±2.2) weeks. All patients ob- tained satisfactory treatment results, except for 3 patients with proximal thigh pain, 2 with pulmonary in- fection occurred and 1 with thrombs of lower limb vein. Harris post trauma hip function score was (88.5 ± 6.3) points. Conclusion PFNA is an effective way for femoral unstable intertrochanteric fractures in the elderly, for it is characterized by short operation time, less blood loss and stable fixation.

We have reformed our patterns and methods of graduation examination of the medical majors. That is the multi-stage comprehensive graduation examination of the clinical interns, which consists of 70% close written test of clinical theories,20% practical test of clinical skills and also oral test of related theories, and 10% writing of the medical documents. It has proved that these measures have improved the interns' attitude toward practice, aroused their initiative and positivity, and led the practitioners to attach more importance to the combination of clinical practice and theories, thus leading to better clinical education.