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.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

OBJECTIVE: To explore clinical effect of early incision and decompression combined with screw fixation in treating Lisfranc injury and foot osteofascial compartment syndrome. METHODS: Clinical data of 5 patients with Lisfranc injury and foot osteofascial compartment syndrome were retrospective analysized from January 2017 to December 2018, including 4 males and 1 female, aged from 19 to 62 years old. All patients were suffered from closed injuries. The time from injury to treatment ranged from 1 to 14 h. According to Myerson classification, 1 patient was type A, 1 patient was type B, and 3 patients were type C. All patients were performed early incision decompression and screw fixation. Maryland foot functional scoring standard at 12 months after opertaion was used to evaluate clinical effect. RESULTS: All patients were followed up for 10 to 48 months. All fractures were achieved bone union, and healing time ranged from 3 to 9 months. All metatarsal and tarsal joints were reached to anatomical reduction. No infection, osteomyelitis, loosening or breaking of internal fixation occurred. Postopertaive Maryland foot function score at 12 months was from 44 to 97, and 2 patients got excellent result, 2 good, and 1 poor. CONCLUSION Early incision and decompression with screw fixation for the treatment of Lisfranc injury and foot osteofascial compartment syndrome, which has advantages of simple opertaion, thoroughly decompression, screw fixation does not occupy space, stable decompression and fixation, and could receive satisfied clinical effect.
Adult ; Bone Screws ; Compartment Syndromes/surgery* ; Decompression ; Female ; Foot Injuries ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tarsal Joints ; Treatment Outcome ; Young Adult

Objective To analyze and summarize the treatment strategies for unstable angina with no-reflow phenomenon after PTCA during early percutaneous interventional procedures.Methods A total of 32 cases with unstable angina were divided into two groups:one group with drug therapy and the other group with drug therapy and thrombus aspiration catheter.The patients were chosen when there was no-reflow phenomenon after PTCA during early percutaneous interventional procedures and their clinical data were compared and analyzed.Blood flow TIMI grade,myocardial perfusion grade (MBG),TIMI myocardial perfusion (TMP) grade and other indexes were observed and recorded.Results The general conditions had no statistical difference between two groups.Compared with the drug therapy group,the proportion of patients with TIMI,MBG and TMP grade 3 was higher in aspiration and drug therapy group (89％ VS 71％ P＜0.05).Conclusion Drug therapy and thrombus aspiration catheter in treatment helps to improve myocardial perfusion level for unstable angina with no no-reflow phenomenon after PTCA during early percutaneous interventional procedures.

Objective To evaluate the feasibility and effect of three-points ablation approach in in treatment of typical atrial flutter guided by CARTO. Methods Twenty-six patients with typical atrial flutter diagnosed by ECG and electrophysiological study (EPS) were enrolled in this study. Activation sequence mapping and linear ablation were performed in 11 patients (conventional group) . Three-points guided linear ablation with CARTO system was performed in another15 patients (three-points group) . Results There was no significant difference in the success rate between the two groups. Both the procedure and fluoroscopic time in three-points group were significantly shorter than that in conventional group [(72.66±29.82) vs (102.52±32.61) min;(4.26±2.76) vs (7.32±3.16) min] . Conclusions The three-points ablations approach is as safe and effective as conventional ablation approach in treatment of typical atrial flutter;however,the former can significantly shorten the procedure time and fluoroscopy time.

Objective To study the effect of implanted stent or selected operation in patients with acute occlusion of right coronary artery during the emergency coronary arteriongraphy. Methods Forty-three patients with acute occlusion of right coronary artery who underwent the emergency coronary arteriongraphy were divided into two groups: the implanted stent group ( n = 23) during the emergency coronary arteriongraphy and the selected operation group (n =20) during the emergency coronary arteriongraphy . Then we observed the general data, the coronary artery pathological changes, preoperative and postoperative thrombus, the blood flow, remained stenosis and the prognosis. Results The implanted stent group was similar to the control group in general condition, but implanted stent group was significantly different from the control group in the near, intermediate and distal coronary artery pathological changes ( <0.05) . The control group was significantly different from the implanted stent group in the thrombus and slowly blood flow ( <0.05) . After three months, we reviewed coronary arteriongraphy and selected operation, The implanted stent group was significantly different from the control in the remained stenosis and slowly blood flow (<0.05) . But the implanted stent group was similar to the control groug in the thrombus and new proceeding cardiovascular events. Conclusion When thrombus appears in acute occlusion of right coronary artery, we can implant stent during the emergency coronary arteriongraphy if the thrombus is little, or we can select operation after PTCA on the contrary.

Objective To evaluate the feasibility of catheter ablation of Para-Hisian Atrial Tachycardia guide by CARTO. Method Catheter ablation guided by CARTO was performed after activation map in three patients with Para-Hisian Atrial Tachycardia. Result Successful ablation was got at right atrial in two patients and at non-coronary in one patient. Conclusion Catheter ablation guided by CARTO is safe and efficient for Para-Hisian Atrial Tachycardia.

Objective To discusse the mechanism and clinical significance of bradycardia -hypotension phenomenon which is caused by vagal reflex during and after the RFCA and present the experience of using appropriate measures to decrease the incidence of this situation. Methods The patients who were suffering from tachyarrhythmias and treated by RFCA were divided into two groups. The groups were as follows:148 patients who were not taken special measures in the early stage were selected in control group;1 540 patients who were taken measures to prevent vasovagal reflex were selected in observation group. Result During the RFCA, the incidence of bradycardia -hypotension phenomenon in control group was 13.5% (20/148), the incidence of bradycardia-hypotension phenomenon in observation group was 5.0%(77/1540) (<0.01) .Conclusions The incidence of bradycardia-hypotension phenomenon caused by vagal reflex during the RFCA is related to catheter irritation to the heart,pressure on the vessels and hypovolemia. The incidence of this phenomenon can be decreased obviously by some measures,such as non-restricted diet before RFCA,discretion rehydration during and after the RFCA and hemostasis with appropriate force after extubation. The key to rescue patients successfully are early detection and timely processing.