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 application value of needle-knife accurate fistulo-tomy (NKAF) for difficult biliary cannulation during endoscopic retrograde cholangiopancreato-graphy (ERCP).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 137 patients with difficult biliary cannulation during ERCP at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2021 and December 2022 were collected. There were 51 males and 86 females, aged (69±13)years. All 137 patients received NKAF for cannulation during ERCP. Observation indicators: (1) surgical situations; (2) complications. Measurement data with normal distribution were represented as Mean± SD. Count data were repre-sented as absolute numbers. Results:(1) Surgical situations. Of 137 patients, 136 cases had succe-ssful cannulation, 1 case had failed cannulation with NKAF following unsuccessful double-guidewire technique. In the 136 successful cases, the endoscope was straightened in 42 cases, left in a long position in 37 cases, and maintained in the standard position in 57 cases. The cannulation time was (90±8)s. (2) Complications. The serum amylase at postoperative 6 hours in the 136 successful cases was (163±23)U/L. No patient developed post-ERCP pancreatitis. Of the 136 patients with successful cannulation, one case experienced post-sphincterotomy bleeding, which was observed oozing from the papillary orifice on emergency gastroscopy. The patient was successfully controlled with endoscopic clips.Conclusion:NKAF is safe and effective for difficult biliary cannulation during ERCP.

Objective:To investigate the status and influencing factors of teaching competence of clinical teachers in the affiliated hospitals of University of Chinese Medicine, and provide a reference for improving the teaching competency of clinical teachers.Methods:Using both objective sampling and random sampling methods, 330 clinical teachers from 3 affiliated hospitals of Beijing University of Chinese Medicine were investigated using the Clinical Teaching Competence Scale for Clinical Teachers in Affiliated Hospitals of TCM Universities from January 22 to February 6, 2024. The main statistical analysis methods included statistical description, non-parametric test, and multivariable linear regression.Results:The total score of clinical teachers' teaching competence was (176.83±22.84) points, with a scoring rate of 84.20%. Regression analysis revealed that teaching title ( β=0.053), age ( β=0.003), general self-efficacy ( β=0.009), and the agreeableness ( β=0.012) and openness ( β=0.010) of the Big Five personality traits were the main influencing factors of teaching competence of clinical teachers ( P<0.05). Conclusions:The clinical teachers in the surveyed medical institutions showed relatively high overall teaching competence, but there is still a need to strengthen their teaching abilities. Colleges and universities should adopt measures to comprehensively enhance their teaching competence, such as paying attention to the growth needs of clinical teachers with low professional titles, increasing the motivation for clinical teachers with high professional titles to improve their teaching abilities, establishing mentorship systems for early-career teachers, encouraging clinical teachers to develop self-efficacy, and focusing on cultivating the personality traits of agreeableness and openness in clinical teachers.

Objective To investigate the functional changes of oligodendrocytes in a mouse model of cognitive impairment induced by microwave radiation and the mechanism.Methods C57BL/6N male mice were exposed to S-band microwave at 2.856 GHz and 8 mW/cm2 for 15 min.The rectal temperature of mice was monitored by an optical fiber thermometer during microwave radiation.The changes of autonomous exploration behavior and learning and memory ability of mice on the 1st and 7th days after microwave radiation were detected via the open field test and novel object recognition test.Immunofluorescence was used to detect the expression and distribution of neuroglia-2 proteoglycan(NG2)and myelin basic protein(MBP)in the hippocampus of mice on the 1st and 7th days after radiation.Clemastine fumarate,a drug that promoted the maturation of oligodendrocyte precursor cells was administered by gavage,and the expression levels of brain-derived neurotrophic factor(BDNF)and fibroblast growth factor 2(FGF2)in hippocampal tissues were detected by radioimmunoassay at 1 and 7 days after radiation.The changes of myelin sheath structure an 1 and 7 days after radiation were observed by transmission electron microscopy.The effects of clemastine fumarate on learning and memory impairment induced by microwave exposure in mice were assessed via open field and new object recognition experiments.Results Under the experimental conditions,the rectal temperature in mice caused by microwave radiation increased by less than 1 ℃,which was within the thermal safety range of the body.The open field test showed that compared with the control group,the microwave radiation group didn't change significant in terms of movement speedon the 1st and 7th days,but the time spent exploring in the central area was significantly reducedon the 1st day after radiation(P＜0.05).In the novel object recognition test,the indexes of the mice on the 1st day were significantly reduced(P＜0.05),indicating that the anxiety like behavior and cognitive function of the mice were impaired after microwave radiation.Compared with the control group,the proportion of NG2+area in the hippocampus was significantly decreased(P＜0.05)in the microwave radiation group,while that of MBP+area hardly changed on the 1st day after microwave radiation(P＞0.05).The expression level of oligodendrocyte related BDNF in the hippocampus was significantly decreased(P＜0.05).The myelin of the corpus callosum was broken,and the myelin g ratio was significantly increased(P＜0.05),suggesting that micro wave radiation could reduce the number of oligodendrocyte precursors and damage the secretion and myelin function of oligodendrocyte.Compared with the radiation group,the expression levels of BNDF and FGF2 in the radiation combined with clemastine fumarate group were up-regulated,the myelin g ratio was significantly decreased on the 1st day after radiation(P＜0.05),and the novel object recognition index was significantly increased(P＜0.05).Conclusion Pulsed microwave radiation below the body's fever threshold can cause cognitive dysfunction and other brain damage in mice.The impaired secretion and myelin function of oligodendrocytes and the decreased self-repair ability are the important mechanisms of cognitive dysfunction induced by microwave radiation.

Objective:To investigate the application value of needle-knife accurate fistulo-tomy (NKAF) for difficult biliary cannulation during endoscopic retrograde cholangiopancreato-graphy (ERCP).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 137 patients with difficult biliary cannulation during ERCP at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2021 and December 2022 were collected. There were 51 males and 86 females, aged (69±13)years. All 137 patients received NKAF for cannulation during ERCP. Observation indicators: (1) surgical situations; (2) complications. Measurement data with normal distribution were represented as Mean± SD. Count data were repre-sented as absolute numbers. Results:(1) Surgical situations. Of 137 patients, 136 cases had succe-ssful cannulation, 1 case had failed cannulation with NKAF following unsuccessful double-guidewire technique. In the 136 successful cases, the endoscope was straightened in 42 cases, left in a long position in 37 cases, and maintained in the standard position in 57 cases. The cannulation time was (90±8)s. (2) Complications. The serum amylase at postoperative 6 hours in the 136 successful cases was (163±23)U/L. No patient developed post-ERCP pancreatitis. Of the 136 patients with successful cannulation, one case experienced post-sphincterotomy bleeding, which was observed oozing from the papillary orifice on emergency gastroscopy. The patient was successfully controlled with endoscopic clips.Conclusion:NKAF is safe and effective for difficult biliary cannulation during ERCP.

Objective:To investigate the status and influencing factors of teaching competence of clinical teachers in the affiliated hospitals of University of Chinese Medicine, and provide a reference for improving the teaching competency of clinical teachers.Methods:Using both objective sampling and random sampling methods, 330 clinical teachers from 3 affiliated hospitals of Beijing University of Chinese Medicine were investigated using the Clinical Teaching Competence Scale for Clinical Teachers in Affiliated Hospitals of TCM Universities from January 22 to February 6, 2024. The main statistical analysis methods included statistical description, non-parametric test, and multivariable linear regression.Results:The total score of clinical teachers' teaching competence was (176.83±22.84) points, with a scoring rate of 84.20%. Regression analysis revealed that teaching title ( β=0.053), age ( β=0.003), general self-efficacy ( β=0.009), and the agreeableness ( β=0.012) and openness ( β=0.010) of the Big Five personality traits were the main influencing factors of teaching competence of clinical teachers ( P<0.05). Conclusions:The clinical teachers in the surveyed medical institutions showed relatively high overall teaching competence, but there is still a need to strengthen their teaching abilities. Colleges and universities should adopt measures to comprehensively enhance their teaching competence, such as paying attention to the growth needs of clinical teachers with low professional titles, increasing the motivation for clinical teachers with high professional titles to improve their teaching abilities, establishing mentorship systems for early-career teachers, encouraging clinical teachers to develop self-efficacy, and focusing on cultivating the personality traits of agreeableness and openness in clinical teachers.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

As a prescription for tonifying kidney yang， Youguiwan accords with the pathogenesis of osteoarthritis. Professor LIU Yuan-lu from the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine found that modified Youguiwan had a significant effect on the clinical conservative treatment of osteoarthritis pain with Chinese medicine. There are teams studying the mechanism of Youguiwan in the treatment of osteoarthritis in China， but the profound study of the compound needs the mechanism of each component as support. Youguiwan contains 10 kinds of Chinese medicine， including Rehmanniae Radix Praeparata， Aconiti Lateralis Radix Praeparata， Cinnamomi Cortex， Dioscoreae Rhizoma， Corni Fructus， Cuscutae Semen， Angelicae Sinensis Radix， Eucommiae Cortex， Cervi Cornus Colla， and Lycii Fructus. With more and more attention to the study of Chinese medicine monomer， the amount of related research in this field is increasing. Therefore， it is of great significance to summarize the mechanism of Youguiwan in the treatment of osteoarthritis. Based on the sovereign， minister， assistant， and guide of Chinese medicine in Youguiwan， this paper used China National Knowledge Infrastructure （CNKI）， Pharmacopoeia of the People's Republic of China （2020 edition Vol. 1）， and ChemicalBook platform to understand the active components of each kind of Chinese medicine， and used PubMed to search. The latest research progress of effective monomers that had an intersection with the mechanism of osteoarthritis was summarized， and there were five pharmacological effects including anti-inflammation， pain inhibition， chondrocyte apoptosis， oxidative stress， and extracellular matrix degradation， involving several signaling pathways. The theory of sovereign， minister， assistant， and guide and the molecular mechanism were integrated and discussed， respectively， and finally， they were combined with traditional Chinese medicine theory， providing theoretical references for further study in this direction.

Objective : To investigate the mechanism of AMD3100 reversing the resistance of human hepatocellular carcinoma cells to Sorafenib by regulating carbonic anhydrase IX ( CA9) and chemokine receptor 4 ( CXCR 4 ) . Methods : The Sorafenib resistant cell lines Huh7 / Sor and HepG2 / Sor were established from human hepatocellular carcinoma cells Huh7 and HepG2．The effects of Sorafenib alone or in combination with AMD3100 on the proliferation of Huh7，HepG2，Huh7 / Sor，HepG2 / Sor cells were detected．The difference of invasive ability between Sorafenib resistant cells and non-resistant cells，and the effect of AMD3100 on the invasive ability of hepatocellular carcinoma cells were observed．And the regulation effect of Sorafenib alone or in combination with AMD3100 on the expression of CA9 and CXCR4 proteins in Huh7，HepG2，Huh7 / Sor and HepG2 / Sor cells was detected. Results: Compared with the Control group，AMD3100 (50 μmol / L) increased the inhibitory effect of Sorafenib on the proliferation of Huh7 / Sor and HepG2 / Sor cells (P＜0．05) ．Compared with Huh7 cells，the invasive ability of Sorafenib resistant Huh7 / Sor cells was significantly enhanced (P＜0. 05) ，and AMD 3100 (50 μmol / L) decreased the invasive ability of Huh7 and Huh7 / Sor cells (P＜0．05) ．Compared with Huh7 and HepG2 cells，the protein expression of CA9 and CXCR4 in Huh7 / Sor and HepG2 / Sor cells increased (P＜0. 05) ．AMD3100 (50 μmol / L) down-regulated the protein expression of CA9 and CXCR4 in Huh7，HepG2，Huh7 / Sor and HepG2 / Sor cells (P ＜0. 05 ) . Conclusion AMD3100 can reduce the resistance of human hepatocellular carcinoma cells to Sorafenib by downregulating the expression of CA9 and CXCR4，and enhance the inhibition of Sorafenib on the proliferation and invasion of human hepatocellular carcinoma cells.