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.

Objective:To investigate the impact of plasmapheresis therapy on the clinical efficacy in predicted severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) patients.Methods:The clinical data of 500 HTG-AP patients admitted to 36 medical centers across China in the Chinese Acute Pancreatitis Clinical Trials Group-PERFORM database from November 2020 to June 2023 were retrospectively analyzed. Besides the inclusion and exclusion criteria from PERFORM study, patients who had acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score ≥8 or CRP>150 mg/L on admission were included in the final analyses ( n=189). Patients were categorized into the plasmapheresis group ( n=51) and the routine treatment group ( n=138) according to the triglyceride-lowering therapies they received. General data, laboratory findings, AP severity, and clinical outcomes were recorded. Results:Patients undergoing plasmapheresis had higher initial triglyceride levels, APACHEⅡ score, SOFA score, and more organ failure than those receiving routine medical treatment. Results of multivariable logistic regression models showed that the plasmapheresis group, as compared to the routine treatment group, was neither associated with decreased risk of persistent organ failure within 14 days [54.9% (28/51) vs 37.7% (52/138), OR=0.89, 95% CI 0.36-2.21, P=0.810], nor with reduced incidence of organ failure on day 7 [17.7% (9/51) vs 15.9% (22/138), OR=0.60, 95% CI 0.19-1.88, P=0.378]. There was no significant difference on the dynamic changes of serum triglyceride within the first three days of admission ( P=0.108). Conclusions:Early plasmapheresis is not associated with reduced incidence of persistent organ failure in predicted severe HTG-AP patients.

Objective:To investigate the impact of plasmapheresis therapy on the clinical efficacy in predicted severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP) patients.Methods:The clinical data of 500 HTG-AP patients admitted to 36 medical centers across China in the Chinese Acute Pancreatitis Clinical Trials Group-PERFORM database from November 2020 to June 2023 were retrospectively analyzed. Besides the inclusion and exclusion criteria from PERFORM study, patients who had acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score ≥8 or CRP>150 mg/L on admission were included in the final analyses ( n=189). Patients were categorized into the plasmapheresis group ( n=51) and the routine treatment group ( n=138) according to the triglyceride-lowering therapies they received. General data, laboratory findings, AP severity, and clinical outcomes were recorded. Results:Patients undergoing plasmapheresis had higher initial triglyceride levels, APACHEⅡ score, SOFA score, and more organ failure than those receiving routine medical treatment. Results of multivariable logistic regression models showed that the plasmapheresis group, as compared to the routine treatment group, was neither associated with decreased risk of persistent organ failure within 14 days [54.9% (28/51) vs 37.7% (52/138), OR=0.89, 95% CI 0.36-2.21, P=0.810], nor with reduced incidence of organ failure on day 7 [17.7% (9/51) vs 15.9% (22/138), OR=0.60, 95% CI 0.19-1.88, P=0.378]. There was no significant difference on the dynamic changes of serum triglyceride within the first three days of admission ( P=0.108). Conclusions:Early plasmapheresis is not associated with reduced incidence of persistent organ failure in predicted severe HTG-AP patients.

Objective To explore the effect of protective ventilation strategies based on individualized positive end expiratory pressure(PEEP)regulated by driving pressure(Pd)in infants under OLV.Methods Sixty infants undergoing elective thoracoscopic surgery were randomly divided into the control group and driving pressure group,with 30 cases in each group.The two groups were compared in terms of MAP,HR,tidal volume(Vt),PEEP,Pd,airway peak pressure(Ppeak),and static lung compliance(Cs),and arterial blood gas during OLV before the artificial pneumothorax(T0),10 min(T1),30 min(T2),and 60 min(T3)after the artificial pneumothorax,and right at the end of the artificial pneumothorax(T4).Results There were no significant differences in MAP,HR,and Vt between the two groups at all the time points(P＞0.05).Both groups showed the increase in Pd and Ppeak and decresase in Cs at T1,T2,and T3(all P＜0.05).PaO2 and OI in both group were decreased and PaCO2 was increased at T2(all P＜0.05).Compared with the control group,the driving pressure group presented lower Pd and Ppeak,higher PEEP and Cs at T1,T2,and T3(P＜0.05),and higher PaO2 and OI(P＜0.05)and no significant differences in PaCO2 and FiO2 at T2(P＜0.05).The rate of rescue ventilation during OLV was lower in the driving pressure group(2 cases)than in the control group(9 cases)(6.9%versus 32.4%,P＜0.05).There was no significant difference in the inci-dence of postoperative complications between the two groups(P＜0.05).Conclusion The individualized positive end expiratory pressure(PEEP)regulated by Pd can optimize the PEEP settings upon infant individuals under OLV and improve the compliance and oxygenation of ventilated lung.

【Objective】 To investigate the effect of multiple apheresis platelet donation on platelet indexes and aggregation function in platelet donors, and to analyze the relationship between platelet indexes and their relationship with platelet aggregation rate. 【Methods】 A total of 83 platelet donors were randomly selected from Foshan Central Blood Station from September 2021 to October 2022, and were divided into control group (n= 9, first-time platelet donors or donors with the time interval from the last platelet donation >1 year) and study group (n= 74, repeat platelet donors or donors with the time interval from the last platelet donation ≤ 1 year) according to the times of blood donation. The study group was divided into 4 subgroups: 2-5 times group, 6-10 times group, 11-15 times group and 16 times group. The platelet count(Plt), platelet distribution width (PDW), mean platelet volume (MPV), large platelet ratio (P-LCR), and maximum platelet aggregation rate (MAR) before donation in each group were detected and analyzed. 【Results】 There were no significant differences in Plt, MPV, PDW, P-LCR and MAR between the subgroups and the control group (P>0.05), and there were no significant differences in Plt, MPV, PDW, P-LCR and MAR between each subgroup (P>0.05) .There was a positive correlation between Plt and MAR in blood donors (P<0.05), and the correlation coefficient was 0.445. MPV, PDW and P-LCR were negatively correlated with MAR (P<0.05), and the correlation coefficients were -0.282, -0.233 and -0.217, respectively. Plt was negatively correlated with MPV, PDW and P-LCR (P < 0. 05), and the correlation coefficients were -0.399, -0.307 and -0.339, respectively. MPV, PDW and P-LCR are positively correlated with each other. The correlation coefficient between MPV and PDW was 0.792, that between MPV and P-LCR was 0.863, and tthat between PDW and P-LCR was 0.817. 【Conclusion】 There was no significant effect of multiple platelet donations on Plt, PDW, MPV, P-LCR and MAR in blood donors. Plt has the most significant impact on MAR among platelet indexes of platelet donors.

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 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 explore the diagnosis process and treatment experience of severe coronavirus disease 2019 (COVID-19) patients with heparin resistance (HR).Methods:The medical team of the First People's Hospital of Lianyungang admitted 2 severe COVID-19 patients with HR in intensive care unit (ICU) during their support to the designated hospital for the treatment of COVID-19 patients in Lianyungang City in November 2021. The clinical features, laboratory examinations, imaging features, treatment and prognosis of the two patients were analyzed.Results:Both severe COVID-19 patients received mechanical ventilation, 1 patient was treated with extracorporeal membrane oxygenation (ECMO) support. Both patients were complicated with lower extremity deep venous thrombosis and HR phenomenon under routine dose anticoagulant therapy. The maximum daily dose of unfractionated heparin exceeded 35 000 U (up to 43 200 U), the 2 patients failed to meet the standard of anticoagulation treatment, and the course of disease was prolonged. After that, argatroban was given 0.4 μg·kg -1·min -1 combined with anticoagulant therapy, the activated partial thromboplastin time (APTT) of patients undergoing ECMO could be maintained at 55-60 seconds and the activated coagulation time (ACT) of them could be maintained at 180-200 seconds. After ECMO support or later sequential mechanical ventilation, both patients recovered and were discharged, and deep venous thrombosis was also effectively controlled. Conclusion:HR phenomenon often occurs during the treatment of severe COVID-19 patients, the anticoagulation regimen should be adjusted in time, and the anticoagulation effect combined with argatroban is clear.

Objective To evaluate the clinical value of Headway duo microcatheter combined with Onyx glue in embolization ofmeningiomas.Methods A retrospective analysis on clinical data of 12 patients with meningiomas,admitted to our hospital from December 2015 to March 2017,was performed.According to the blood supply typing ofManelfe meningiomas,5 were type Ⅰ,3 were type Ⅱ,2 were type Ⅲ,and 2 were type Ⅳ.The degrees of embolization were compared by DSA tumor staining before and after embolization;and complications of embolization were recorded.Results Cerebral angiography after embolization demonstrated complete embolization in 5 patients,subtotal embolization in 5,partial embolization in 2,and small amount of embolization in 0.Only 2 had head and face pain in the process of embolization,and these syndromes disappeared once the operation stopped.The mean average blood loss in the surgery was 685 mL and the mean surgical time was 4.45 h.Conclusion Headway duo microcatheter combined with Onyx glue in the embolization of intracranial meningiomas can play a good role in blocking blood flow,and results suggest that this method is safe and effective,worth of clinical promotion.

Objectives To investigate the efficacy and safety of quadruple regimen containing doxycy-cline,amoxicillin and clavulanate potassium in the treatment of Helicobacter pylori(Hp)after the failed initial eradication. Methods A total of 136 patients who had a failed course of initial eradication therapy were randomly divided into four groups. The 46 patients in group A were given rabeprazole,colloidal bismuth tartrate,doxycy-cline,amoxicillin and clavulanate potassium for 14 days). The 45 cases in group B were treated with rabeprazole, colloidal bismuth tartrate,doxycycline,amoxicillin and clavulanate potassium for 10 days. The 45 cases in control group received rabeprazole,colloidal bismuth tartrate,levofloxacin,amoxicillin for 14 days. After 4 weeks of treat-ment,the 13C-urea breath test was performed. The Hp eradication rates,adverse reactions,treatment compliance and cost-effectiveness ratio of the three groups were evaluated. Results A total of 130 patients completed the study. The intention to treat(ITT)and Per-protocol(PP)analyses revealed that the eradication rates of the three groups were 71.74% and 76.74%(group A),71.11% and 72.72%(group B),51.11% and 53.49%(control group),respectively. The ITT and PP of group were significantly higher than those of control group(P < 0.05). But there was no significant difference between group B and control group(P > 0.05). The rates of adverse reac-tions in each group were not statistically significant(P > 0.05),and the patient compliance of three groups was more than 80%. The cost and cost-effectiveness ratio showed that group B < control group < group A. Conclu-sions The quadruple therapy containing doxycycline,amoxicillin and clavulanate potassium as a rescue regimen given for 14 days is safe,effective and with high patient compliance,which is of high clinical significance.