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.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective To investigate the multi spiral computed tomography(MSCT)characteristics of intraductal papillary neo-plasm of the bile duct(IPNB)and to distinguish the benign and malignant ones.Methods The MSCT and clinical data of 23 patients with IPNB confirmed by pathology were analyzed retrospectively.According to the pathology,they were divided into benign and malignant groups,including 12 cases of benign group(7 cases with low to medium grade intraepithelial neoplasia,and other 5 cases with high grade intraepithelial neoplasia)and 11 cases of malignant group with invasive carcinoma.All patients underwent plain and tri-phasic enhanced CT scans of upper abdomen.The enhanced scan included arterial phase,portal phase and delayed phase.The location,size,growth mode,enhancement type,invasion and metastasis,bile duct manifestations and bile duct stones were analyzed.Independent sample t-test was used to count the transverse diameter,longitudinal diameter and aspect ratio of tumor.Chi square test was used to compare the difference in other parameters between benign and malignant groups.Results There were no significant differences between benign and malignant IPNB groups in the location of the disease,the transverse diameter of the tumor,the dilatation of the bile duct and the presence of the stones(P>0.05).However,the significant differences in tumor growth mode,tumor longitudinal diameter and aspect ratio,enhancement type,invasion of bile duct wall and bile duct truncation were found(P<0.05).Conclusion Benign IPNB is common,while the IPNB with diffuse growth,progressive enhancement,invasion of bile duct wall and extrabiliary structures,and distant metastasis may indicate malignance,and the final diagnosis depends on the pathology.

Objective To study the population genetic structure and phylogenetic relationships by combining Y-STR haplotype genetic information from the Han population in Dalian with 32 domestic and foreign groups.Methods Blood samples of 958 Han male volunteers from Dalian were collected.Genetic typing of 42 genetic loci was completed using Y-STR fluorescent reagent kits and capillary electrophoresis.Related forensic parameters were calculated.Nei's standard genetic distances among 33 populations based on 17 Y-STR loci were computed,in order to create a principal coordinate analysis as well as construct a phylogenetic tree.Results The analysis of genetic polymorphisms at 42 Y-STR loci revealed 30 unconventional alleles at 10 loci.Genetic analysis of the population based on 17 Y-STR loci confirmed that Dalian's Han population had the closest genetic distance to the Anshan's Han population,followed by populations from Henan,Heilongjiang,Jilin,Shandong,and Chongqing.Furthermore,the genetic distances between the Han population in Dalian and the Qiang population in Beichuan or the Miao population in Guizhou were relatively closer than that to the Manchu population living in Liaoning.Conclusion The genetic distance between the Han population in Dalian and other groups is not entirely proportional to ethnicities and geographical proximity.Both population migration and ethnic assimilation or isolation may have influence on it.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 µg/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 µg/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Objective    To investigate the effectiveness and safety of robotic lobectomy in clinical N0 lung malignant tumor≥3 cm. Methods    We retrospectively analyzed the clinical data of 182 patients with lung malignant tumor≥3 cm receiving robotic or thoracoscopic lobectomy at Shanghai Chest Hospital in 2019. The patients were divided into a robotic surgery group (RATS group) and a thoracoscopic surgery group (VATS group). There were 39 males and 38 females with an average age of 60.55±8.59 years in the RATS group, and 51 males and 54 females with an average age of 61.58±9.30 years in the VATS group. A propensity score matching analysis was applied to compare the operative data between the two groups. Results    A total of 57 patients were included in each group after the propensity score matching analysis. Patients in the RATS group had more groups of N1 lymph node dissected (2.53±0.83 groups vs. 2.07±0.88 groups, P=0.005) in comparison with the VATS group. No statistical difference was found in operation time, blood loss, postoperative hospital stay, number of N1 and N2 lymph nodes dissected, groups of N2 lymph node dissected, lymph node upstage rate or postoperative complications. The hospitalization cost of RATS was higher than that of VATS (P<0.001). Conclusion    In contrast with thoracoscopic lobectomy, robotic lobectomy has similar operative safety, and a thorough N1 lymphadenectomy in patients with clinical N0 lung malignant tumor≥3 cm.

Objective    To compare the perioperative outcomes between robot-assisted complex segmentectomy and simple segmentectomy for stage ⅠA non-small cell lung cancer (NSCLC). Methods    The clinical data of 285 patients with NSCLC undergoing robot-assisted thoracic surgery (RATS) in our hospital from January 2015 to August 2021 were retrospectively analyzed. There were 105 males and 180 females aged 23-83 years. The patients were divided into a complex segmentectomy group (n=170) and a simple segmentectomy group (n=115) according to tumor location and surgical method. The clinical pathological baseline characteristics and perioperative outcomes between the two groups were compared, including operative time, blood loss volume, dissected lymph nodes, conversion rate, postoperative duration of drainage, postoperative hospital stay, the incidence of persistent air leakage and postoperative 30 d mortality. Results    There was no statistical difference in baseline data between the two groups (P>0.05). No postoperative 30 d death was observed. One patient in the complex segmentectomy group was transferred to thoracotomy. No statistical difference was observed between the two groups in the operative time (97.36±38.16 min vs. 94.65±31.67 min, P=0.515),  postoperative duration of drainage (3.69±1.85 d vs. 3.60±1.90 d, P=0.679), postoperative hospital stay (4.07±1.85 d vs. 4.05±1.97 d, P=0.957), dissected lymph nodes (5.15±3.53 vs. 5.13±2.93, P=0.952), incidence of blood loss volume<100 mL (98.2% vs. 99.1%, P=0.650), and incidence of postoperative persistent air leakage (6.5% vs. 5.2%, P=0.661). Conclusion    The safety and effectiveness of robot-assisted complex segmentectomy and simple segmentectomy are satisfactory in the treatment of stage ⅠA NSCLC. The perioperative results of RATS complex segmentectomy and simple segmentectomy are similar.

Objective:To investiagte the ability of albumin-indocyanine green (ALICE) score, albumin-bilirubin (ALBI) score and Child-Pugh score in predicting postoperative liver failure (PHLF) in patients with hepatocellular carcinoma, and to determine the clinical value of ALICE score.Methods:The clinical data of 397 patients with hepatocellular carcinoma who underwent hepatectomy in the Department of Hepatobiliary and Pancreatic Surgery, Jinhua Hospital Affiliated to Zhejiang University from June 2015 to June 2021 were retrospectively analyzed, including 350 males and 47 females, aged (58.9±11.2) years. Univariate and multivariate logistic regression were used to analyze the risk factors of PHLF. The predictive ability of ALICE score for PHLF was evaluated by receiver operating characteristic (ROC) curve, and compared with ALBI score and Child-Pugh score.Results:There were 74 patients with PHLF and 323 patients without PHLF. Multivariate logistic regression analysis showed that Child-Pugh score ( OR=1.630, 95% CI: 1.251-2.486, P=0.034), ALBI score ( OR=1.863, 95% CI: 1.028-3.119, P=0.049) and ALICE score ( OR=1.759, 95% CI: 1.216-3.078, P=0.038) were independent risk factors for PHLF in patients with hepatocellular carcinoma, and the risk of PHLF increased with the increase of grade. The area under the ROC curve of ALICE score predicting PHLF in patients with hepatocellular carcinoma was 0.613 (95% CI: 0.564-0.662), the area under the ALBI score was 0.612 (95% CI: 0.563-0.661), and the area under the Child-Pugh score was 0.555 (95% CI: 0.505-0.605). The ALICE score was better than the Child-Pugh score, and the difference was statistically significant ( z=2.04, P=0.041). In small liver resection patients, ALICE score was better than Child-Pugh score ( z=2.61, P=0.009). There was no significant difference betwenn ALICE score and ALBI score ( z=0.06, P=0.954). Conclusion:ALICE score can predict the occurrence of PHLF in patients with hepatocellular carcinoma, especially in patients with small liver resection, its value is similar to ALBI score, but better than Child-Pugh score.

【Objective】 To study the frequency, Rh phenotypes and molecular & biological background of D-elute (D^el) phenotype in RhD-negative blood donors in Dalian. 【Methods】 A total of 355 serologically RhD-negative samples between November, 2018 and October, 2019 in Dalian Blood Center were collected, and tested for RhC, c, E, e phenotypes using monoclonal antibodies and anti-D adsorption/elution test. DNA was extracted by magnetic bead selection. RHD 1227G>A mutation was detected by melting curve analysis. All RHD exons were sequenced by Sanger sequencing. 【Results】 Among 355 serologically RhD-negative blood donors, 55 (15.5%) were identified as D^el and the remaining 300 cases (84.5%) were true RhD negative. Ccee (45/55, 81.8%) was the predominant Rh phenotype among 55 D^el cases while ccee (210/300, 70.0%) was the most prevalent Rh phenotypes in 300 true RhD negative cases. In 55 D^el cases, 51 (92.7%) had RHD 1227G>A mutation, and the other 4 cases(7.3%) had mutations in other sites. 【Conclusion】 The frequency of D^el was 15.5% in serologically RhD-negative blood donors in Dalian, with Ccee being the most prevalent Rh phenotype and RHD 1227G>A the most common gene mutation.