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.

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

Objective:To evaluate the feasibility of " two-stitch" fashion in laparoscopic pancreaticojejunostomy (PJ) for patients with fine pancreatic duct (<3 mm).Methods:Clinical data of 32 patients with pancreatic duct diameter <3 mm undergoing laparoscopic PJ using the " two-stitch" fashion between Apr 2021 and Jun 2024 were retrospectively analyzed, including 20 males and 12 females, aged (61.2±23.7) years. Among the patients, there were 23 (71.9%) patients of periampullary tumor and 9 (28.1%) of central pancreatic tumor. 23 (71.9%) patients underwent laparoscopic pancreatoduodenectomy (LPD) and nine (28.1%) underwent laparoscopic central pancreatectomy (LCP). All patients underwent the " two-stitch" fashion of laparoscopic PJ (one stitch each on the ventral and dorsal sides of pancreas for duct-to-mucosal anastomosis). The operation time, PJ time, postoperative hospital stay, postoperative complications (pancreatic fistula, gallbladder leakage, abdominal cavity infection, etc) and mortality were recorded.Result:All patients underwent the " two stitch" laparoscopic PJ successfully, 23(71.9%) patients underwent laparoscopic pancreatoduodenectomy (LPD) and nine (28.1%) underwent laparoscopic central pancreatectomy (LCP). The operation time was (279.3±115.8) min, the PJ time was (31.9±12.2) min, and the postoperative hospital stay was (13.4±8.3) d. Grade B pancreatic fistula occurred in six cases (18.8%, four of LPD and two of LCP), delayed gastric emptying in one case of LPD (3.1%), abdominal infection in three cases (9.4%, two of LPD and one of LCP), biliary fistula in two cases (6.3%, LPD). There were no grade C pancreatic fistula. All patients with postoperative complications were managed with conservative treatment.Conclusion:Laparoscopic " two stitch" PJ for patients with fine pancreatic duct (<3 mm) is safe and feasible.

IL-32 is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory properties.It has been proved that expression of IL-32 increases with progression of gastric mucosal diseases and severity of gastric cancer(GC),thus participating in process of gastric"inflammation-cancer"transformation.However,how IL-32 affects malignant transformation of gastric"inflamma-tion-cancer"and finally leads to adverse outcome of GC invasion and migration is still controversial.In order to better clarify regulatory effect and possible mechanism of abnormal expression of IL-32 on different histopathological stages of gastric"inflammation-cancer"transformation,and to explore new directions and breakthroughs in molecular mechanism of early truncation and treatment of gastric precancerous lesion(GPL),we searched literatures related to IL-32 in six authoritative databases at home and abroad,such as Pubmed,Web of Science and CNKI,in past 30 years.It was found that pathogenicity or protective function of IL-32 in different histo-pathological stages of gastric"inflammation-cancer"transformation depended on its different subtypes,secretory forms,surrounding cytokine environment,disease status and genetic factors.IL-32 may regulate polarization of macrophages through NF-κB,MAPK,COX2,PR3,IDO,NOD,PKCδ,FAK and STAT3,amplify or inhibit chronic inflammatory stimulation of gastric mucosa,and thus participate in process of gastric"inflammation-cancer"transformation.Our new understanding of role of IL-32 in different stages of Cor-rea cascade may contribute to development of cytokine-directed therapy,and therapy aimed at regulating different alternative splicing subtypes of IL-32 and targeting IL-32 signals can be used as a new strategy for medical treatment of GPL and GC in future.

Objective Based on the WSR methodology,a three-dimensional integrated perspective of Wuli,Shi-li,and Renli dimensions was used to sort out the logical relationships and architectures among negative defensive medical governance strategies,forming the priority governance strategies for improving negative defensive medical care.Methods Based on the literature research method and the expert consultation method,the governance strate-gy and the conceptual connotation of WSR are classified into items,and the role relationship in the complex sys-tem of passive defensive medical governance is clarified through the WSR methodology.Results A collection of 40 negative defensive medicine governance strategies has been developed,comprising 8 strategies in the Wuli dimen-sion,23 strategies in the Shili dimension,and 9 strategies in the Renli dimension.Conclusion The WSR methodology provides a three-dimensional systemic perspective for governance strategies against negative defen-sive medicine.Addressing this issue requires comprehensive and systematic governance strategies.

Objective Based on the WSR methodology,a three-dimensional integrated perspective of Wuli,Shi-li,and Renli dimensions was used to sort out the logical relationships and architectures among negative defensive medical governance strategies,forming the priority governance strategies for improving negative defensive medical care.Methods Based on the literature research method and the expert consultation method,the governance strate-gy and the conceptual connotation of WSR are classified into items,and the role relationship in the complex sys-tem of passive defensive medical governance is clarified through the WSR methodology.Results A collection of 40 negative defensive medicine governance strategies has been developed,comprising 8 strategies in the Wuli dimen-sion,23 strategies in the Shili dimension,and 9 strategies in the Renli dimension.Conclusion The WSR methodology provides a three-dimensional systemic perspective for governance strategies against negative defen-sive medicine.Addressing this issue requires comprehensive and systematic governance strategies.

Objective:To evaluate the feasibility of " two-stitch" fashion in laparoscopic pancreaticojejunostomy (PJ) for patients with fine pancreatic duct (<3 mm).Methods:Clinical data of 32 patients with pancreatic duct diameter <3 mm undergoing laparoscopic PJ using the " two-stitch" fashion between Apr 2021 and Jun 2024 were retrospectively analyzed, including 20 males and 12 females, aged (61.2±23.7) years. Among the patients, there were 23 (71.9%) patients of periampullary tumor and 9 (28.1%) of central pancreatic tumor. 23 (71.9%) patients underwent laparoscopic pancreatoduodenectomy (LPD) and nine (28.1%) underwent laparoscopic central pancreatectomy (LCP). All patients underwent the " two-stitch" fashion of laparoscopic PJ (one stitch each on the ventral and dorsal sides of pancreas for duct-to-mucosal anastomosis). The operation time, PJ time, postoperative hospital stay, postoperative complications (pancreatic fistula, gallbladder leakage, abdominal cavity infection, etc) and mortality were recorded.Result:All patients underwent the " two stitch" laparoscopic PJ successfully, 23(71.9%) patients underwent laparoscopic pancreatoduodenectomy (LPD) and nine (28.1%) underwent laparoscopic central pancreatectomy (LCP). The operation time was (279.3±115.8) min, the PJ time was (31.9±12.2) min, and the postoperative hospital stay was (13.4±8.3) d. Grade B pancreatic fistula occurred in six cases (18.8%, four of LPD and two of LCP), delayed gastric emptying in one case of LPD (3.1%), abdominal infection in three cases (9.4%, two of LPD and one of LCP), biliary fistula in two cases (6.3%, LPD). There were no grade C pancreatic fistula. All patients with postoperative complications were managed with conservative treatment.Conclusion:Laparoscopic " two stitch" PJ for patients with fine pancreatic duct (<3 mm) is safe and feasible.

The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.

Objective To explore clinical effect of Jiawei Sangju decoction combined with oseltamivir in the treatment of influenza B complicated with benign acute childhood myositis(BACM).Methods Sixty children with influenza B complicated with BACM hospitalized in the Department of Pediatrics,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2021 to January 2024 were selected and divided into control group and study group according to random number table method,with 30 cases in each group.The control group was treated with oseltamivir,and the study group was treated with Jiawei Sangju decoction combined with oseltamivir.The clinical efficacy,symptom improvement time and aspartate transaminase(AST),alanine transaminase(ALT),creatine kinase(CK),creatine kinase isozyme(CK-MB),lactate dehydrogenase(LDH)and myoglobin(Mb)before and after treatment were compared between two groups.Results After treatment,the total effective rate of study group was significantly higher than that of control group(χ2=5.455,P=0.020).The duration of fever and leg pain relief in study group were significantly shorter than those in control group(P<0.05).After 5 days of treatment,the levels of AST,CK,CK-MB,LDH and Mb in two groups were significantly lower than before treatment(P<0.05),and the levels of AST,CK,CK-MB,LDH and Mb in study group were significantly lower than those in control group(P<0.05).Conclusion Jiawei Sangju decoction combined with oseltamivir can improve the symptoms of influenza B with BACM,reduce the levels of muscle enzyme and Mb,and have a positive effect on the prognosis of children.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.