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.

ObjectiveTo determine the pharmacodynamic substance basis of Epimedii Folium（EF） and Epimedii Wushanensis Folium（EWF） in promoting osteogenic differentiation， and to establish a method to analyze the material basis of Chinese materia medica based on the correlation between chemical fingerprint and cellular metabolomics. MethodThe chemical fingerprints of 15 batches of EF with 4 species and 3 batches of EWF were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， and partial least squares-discriminant analysis（PLS-DA） was used to analyze the peak areas of chemical fingerprints of samples. The effects of different samples on proliferative activity of MC3T3-E1 osteoblast precursors， as well as the activity of alkaline phosphatase（ALP） in osteoblasts were detected by cell counting kit-8（CCK-8） and enzyme-linked immunosorbent assay（ELISA）. At the same time， UPLC-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to analyze the effects of different samples on the metabolomics of MC3T3-E1 cells， then metabolic peak table of osteogenic differentiation cells was constructed， and pharmacodynamic index mean Y₀ was introduced into the peak table. PLS was used to calculate mean Y₀ of each group， and the mean Y₀ was added to the peak table of chemical fingerprint to construct the correlation between chemical fingerprint and cell metabolome， the pharmacodynamic components of EF and EWF that promote bone differentiation were screened according to variable importance in the projection（VIP） value>1. The pharmacodynamic effects of EF and EWF were evaluated according to the mean Y₀ of each group. ResultThe chemical fingerprints of EF with different origins and EWF were completely separated. Compared with the blank group， the activity of MC3T3-E1 cells in EF and EWF groups was significantly increased， the activity of ALP in the Epimedium brevicornu（Gansu province）， E. koreanum and E. pubescens groups was significantly increased（P<0.05）. The results of cell metabolomics showed that the blank group and the model group had an obvious trend of separation. EF with different origins and EWF had different distance from the model group， indicating that EF with different origins and EWF had different effect on promoting osteogenic differentiation. Chemical fingerprint-cell metabolomics integration analysis screened 9 components closely related to the efficacy of EF and EWF， including diphylloside B， epimedin C， icariin， baohuoside Ⅰ， yinyanghuo B， β-anhydroicaritin， magnoflorine， cryptochlorogenic acid and quercetin. E. koreanum had the strongest effect on promoting osteogenic differentiation. ConclusionThis study determined that the material basis of EF and EWF promoting osteogenic differentiation were mostly flavonoids， alkaloids and organic acids， which provided ideas and methods for the screening of pharmacodynamic components and the prediction of therapeutic effect of Chinese materia medica.

While lobectomy is the standard surgical procedure for early-stage non-small cell lung cancer (NSCLC), sublobectomy (segmentectomy/wedge resection) has been gaining progress in early-stage peripheral NSCLC in recent years because it preserves more lung parenchyma and has the advantages of good postoperative lung function, relatively less trauma, and faster recovery. However, there has been a lack of standardized randomized clinical trials to study the survival benefits of sublobectomy. The results of a high-profile study from the USA, CALGB140503, have been the subject of intense industry debate since its presentation at the 2022 World Conference on Lung Cancer (IASLC WCLC 2022). The study, which was published in The New England Journal of Medicine on February 9, 2023, was designed to investigate whether sublobectomy was not inferior to lobectomy in terms of survival in patients with early-stage peripheral NSCLC (tumor diameter≤2 cm). The results showed that sublobectomy was not worse than lobectomy for survival in patients with T1aN0M0 peripheral NSCLC with tumor diameter≤2 cm and pathologically confirmed negative hilar and mediastinal lymph nodes. Sublobectomy, including anatomical segmentectomy and wedge resection is an effective NSCLC treatment. The results of this study provide strong evidence for the improved outcomes of sublobectomy in terms of lung function protection and are expected to promote the further use of sublobectomy. However, given the limitations of this study, whether sublobectomy, especially wedge resection, can become a standard procedure still needs to be explored. This paper presents an interpretation of this study and we invite experts in the field to discuss its usefulness in guiding clinical practice and summarise its limitations.

Objective:To explore the application of laparoscopic training in the standardized residency training of pediatric general surgery.Methods:A total of 36 rotating residents who received the standardized residency training in the department of pediatric general surgery of Shenzhen Children's Hospital from January 2017 to December 2019 were selected for laparoscopic training. The training content includes the study and training of laparoscopic theory knowledge, laparoscopic surgery video, skills operation of simulated operating system. Assessment was conducted before and after the training, and statistical analysis was performed to compare the difference of scores before and after the training. The self-evaluation of resident's learning efficiency and the satisfaction with teachers were investigated by questionnaires. SPSS 20.0 was used for paired t-test. Results:After receiving the standardized residency training of pediatric general surgery, the theoretical knowledge and cognition of the application on pediatric general laparoscopic surgery were significantly improved among the 36 residents. The time that the skills spent in vitro simulation box during the simulated operation training was significantly reduced after training, with a statistically significant difference ( P < 0.05). According to the questionnaire survey, resident's satisfaction with self-evaluation of learning efficiency was 97.22% (35/36), their satisfaction with teachers was 94.44% (34/36), and their satisfaction with teaching curriculum was 100.00% (36/36). Conclusion:Laparoscopic training can effectively improve the clinical practice ability of pediatric general surgery residents, which is worthy of promotion.

Objective:To evaluate the safety of total artery coronary artery bypass grafting(CABG) in patients with coronary heart disease and the short- and mid-term clinical outcomes.Methods:A retrospective analysis of the clinical data of 100 patients who underwent CABG treatment in the First Affiliated Hospital of Guangxi Medical University from January 2016 to July 2021. Of these, 50 patients were selected for comparison(TACR) with the left internal thoracic artery and radial artery(RA) as grafts. However, the left internal thoracic artery and the great saphenous vein were used as grafts in other 50 patients were selected as controls(NCR). The clinical data of preoperative, perioperative, and postoperative(3 months, 6 months, 1 year and 5 years) for two groups were compared.Results:In the perioperative period, TACR group was inferior to the control in both operation time and 24 h postoperative drainage. But the peak value of hypersensitive troponin T was lower than that of NCR. There was no significant difference between the two groups in terms of mechanical ventilation time and perioperative mortality. There was no significant difference between the two groups in terms of left ventricular ejection fraction(LVEF), recurrent angina, left ventricular end-diastolic diameter and recurrent myocardial infarction at 3 and 6 months after operation. LVEF in TACR was better than that in NCR at 1 year and 5 years postoperatively.Conclusion:The clinical effect of CABG with RA as bridge vessel carried out in our center is obvious. TACR is safe and feasible due to its good mid-term efficacy and is not likely to cause postoperative complications.

Objective:To study the curative effect of platelet-rich plasma (PRP) combined with internal fixation with hollow screws on femoral neck fractures.Methods:The clinical data of 160 patients with femoral neck fracture were retrospectively analyzed who had been treated by internal fixation with hollow screws at Orthopedic Department Ⅲ, The Second Affiliated Hospital to Luohe Medical College from May 2012 to May 2018. According to whether PRP was used or not to assist their internal fixation, they were divided into a PRP group ( n=80) and a control group ( n=80). In the PRP group, there were 46 males and 34 females with an age of 52.3 years±7.6 years, and one case of type Ⅰ, 5 cases of type Ⅱ, 57 cases of type Ⅲ and 17 cases of type Ⅳ by the Garden classification. In the control group, there were 41 males and 39 females with an age of 50.6 years ± 7.3 years, and 2 cases of type Ⅰ, 7 cases of type Ⅱ, 51 cases of type Ⅲ and 20 cases of type Ⅳ by the Garden classification. The 2 groups were compared in terms of fracture healing time, nonunion, femoral head necrosis and Harris hip scores. Results:The 2 groups were comparable because their preoperative general data showed no significant differences ( P>0.05). The 160 patients obtained follow-up for 12 to 36 months. The PRP group showed significantly shorter fracture healing time (4.3 months ± 1.0 months), significantly lower incidences of nonunion [0% (0/80)] and avascular necrosis of femoral head [3.8% (3/80)] than the control group [7.3 months ± 1.3 months, 7.5% (6/80) and 15.0% (12/80), respectively] (all P< 0.05). The Harris scores at 6 and 12 months after operation for the PRP group (88.7±5.3 and 94.2±4.8) were significantly higher than those for the control group (81.4±4.6 and 84.2±5.2) (both P<0.05). Conclusion:In the treatment of femoral neck fractures, compared with internal fixation with hollow screws alone, platelet rich plasma combined with internal fixation with hollow screws can significantly shorten fracture healing time, reduce incidence of avascular necrosis of the femoral head and improve functional recovery of the hip joint.

Objective To investigate the mechanism of miRNA-129-5p in epithelial-mesenchymal transition (EMT)of biliary atresia.Methods Constructed bile duct epithelial EMT cell model (the experimental group) induced by TGF-β1,detected the expressions of EMT related markers and miRNA-129-5p.While miRNA-129-5p precursor was transfected,the expressions of EMT related markers and extracellular matrix were contrasted between the original and the renovated biliary epithelial cells.Results In the experimental group,extrahepatic bile duct showedEMT,the expression of miRNA-129-5p was decreased (P＜0.05),overexpression of miRNA-129-5p could inhibit the progression of EMT (P＜0.05).Conclusion miRNA-129-5p may relate to EMT by regulating the expression of TGF-β1.

Objective To study the curative efficacy and safety of single-unit umbilical cord blood transplantation (sUCBT) for malignant hematologic diseases,which is provided by China's public cord blood bank.Methods We retrospectively analyzed 409 cases of malignant hematologic diseases who accepted myeloablative single-unit unrelated donor UCBT without ATG at our center between May 2008 and December 2016.A comparative analysis was made on the total nuclear cells (TNC) of the umbilical cord blood before freezing and after thawing,the cells of CD34+,the recovery rate of cells and the clinical effect of UCBT.Result 409 units of umbilical cord blood used in UCBT respectively came from eight China's public cord blood banks.The average TNC of 409 units of umbilical cord blood before freezing and after the tubular recovery were respectively 18.5 × 108 and 16.34 × 108 (p =0.000).The average recovery rate of the tubular recovery was 88.5％,and there was significant difference among cord blood banks (P =0.000).The average TNC of umbilical cord blood before freezing and transfusion were respectively 18.5 × 108 and 15.86 × 108 (p =0.000).The average recovery rate of umbilical cord blood transfusion was 85.9％,with the difference being significant among cord blood banks (P =0.000).The average number of CD34+ cells before freezing and after the tubular recovery was 11.18 × 106and 8.68 × 106 (p =0.000).The average recovery rate of CD34+ cells after the tubular recovery was 80.75 ％,with the difference being significant among the cord blood banks (P =0.000).At 42nd day after UCBT,the cumulative incidence of neutrophil engraftment was 95.4％,and the median time of the engraftment was 17 days (11-38 days).The cumulative incidence of platelet engraftment at 120th day was 84.6％,and the median time of the engraftment was 36 days (14-93 days).The cumulative incidence of erythrocyte engraftment at 60th day was 92％,and the median time of engraftment was 22 days (9d-60 days).After the umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of engraftment.The P values for cumulative incidence of neutrophil,platelet and erythrocyte engraftment were respectively 0.004,0.01 and 0.000 2,with the differences being statistically significant.At 100th day after UCBT,the cumulative incidence of Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees of acute graft-versus-host disease (aGVHD) was respectively 28.63％ and 15.7％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of aGVHD.There was no significant difference between Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees (P =0.809 and 0.68 respectively).At 3rd year after UCBT,the cumulative incidence of relapse was 15.89％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the cumulative incidence of relapse (P =0.898).At 3rd year after UCBT,the overall survival (OS) rate and disease free survival (DFS) rate were respectively 66.7％ and 59％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in OS and DFS.There was no significant difference in OS and DFS (P =0.566 and 0.703 respectively).At 3rd year after sUCBT,the rate of graft-versus-host diseases/relapse-free survival (GRFS) was 54.3％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the rate of GRFS (P =0.449).Conclusion The umbilical cord blood provided by China's public cord blood bank was used in UCBT.It has a high safety and good efficacy in treating malignant hematologic diseases.But it needs to set up the standardized and normalized quality-control system of umbilical cord blood for China's public cord blood bank.

Objective To investigate and evaluate the clinical signiifcance of lfexible ureteroscopy in computed tomography urography negative patients with upper urinary tract hematuria. To improve the diagnostic rate of patients with upper urinary tract hematuria. Methods We retrospectively reviewed the cases of 10 computed tomography urography negative patients with upper urinary tract hematuria. The age ranges from 38 to 75 years old, and the average of them is 45.2 years old. The patients consist of 7 male patients and 3 female patients. Among them, 4 cases were on the left upper urinary tract cases, 6 cases were right upper urinary tract. All patients received lfexible ureteroscopy to conifrm the diagnosis and take the relevant treatment. Results In the total of 10 patients, 3 patients (30%) were diagnosed with tumors of renal pelvis, a renal arteriovenous ifstula was found in 1 case (10%), 3 patients (30%) were considered non-specific inflammation, other 3 patients (30%) had no obvious abnormalities. Conclusions Flexible ureteroscopy has significantly clinical diagnosis in computed tomography urography negative patients with upper urinary tract hematuria.