Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

The apprenticeship education of Traditional Chinese medicine(TCM)is an important pathway for the cultivation of talents in TCM education.The combination of institutional education and apprenticeship education is considered to be the most suitable educational model that aligns with the inherent characteristics of TCM education.The current status of TCM education in western medical institutions and the main challenges include the difficulty in transitioning between western and Chinese medical reasoning and limited clinical internship hours for TCM.The strengths and features of TCM apprenticeship education lie in cultural heritage,classical teachings,mentorship,practice orientation and personalized education.Therefore,integration of TCM apprenticeship education and clinical internships for western medical students represents a new educational model for medical undergraduates.

Objective To analyze the consistency between computer tomography angiography(CTA)and digital subtraction angiography(DSA)in evaluating the global limb anatomic staging system(GLASS)stage of patients with chronic limb-threatening ischemia(CLTI).Methods The clinical data of patients with CLTI,who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University of China to receive treatment between January 2017 and December 2020,were retrospectively analyzed.Taking the DSA assessment as the gold standard,the consistency of CTA and DSA in evaluating the GLASS stage of patients with CLTI was analyzed.Results In the assessment of GLASS stage of CLTI,CTA showed strong agreement with DSA.The weighted Kappa coefficient of CTA and DSA for the staging of femoropopliteal segment was 0.798(95％CI=0.722-0.873,P＜0.01),and the weighted Kappa coefficient of CTA and DSA for the staging of infrapopliteal artery segment was 0.785(95％ CI=0.725-0.845,P＜0.0l).For the overall staging of GLASS,the weighted Kappa coefficient of CTA and DSA was 0.832(95％ CI=0.752-0.91 1,P＜0.01).All the above results indicated that a very strong consistency existed between CTA and DSA in evaluating the GLASS stage of patients with CLTI.Conclusion CTA examination of lower limb can accurately evaluate GLASS score and stage of CLTI patient's target lesions,which is helpful in diagnosing lower extremity arteriosclerosis occlusion disease as well as in assessing the technical difficulty degree of its revascularization operation.(J Intervent Radiol,2024,33:300-303)

Objective:To explore the clinical characteristics and outcomes of type 2 autoimmune pancreatitis (AIP) and compare with type 1 AIP.Methods:Clinical data of the patients diagnosed with type 2 AIP by the International Consensus on diagnostic criteria of AIP at Peking Union Medical College Hospital from January 2001 to December 2022 were retrospectively analyzed, and type 1 AIP patients diagnosed in Peking Union Medical College Hospital from January 1985 to December 2016 were collected as controls. The clinical symptoms, treatments and follow-ups were analyzed.Results:A total of 25 patients with type 2 AIP were included, of which 16 cases (64.0%) were pathologically confirmed cases (13 cases by endoscopic ultrasound puncture, 2 cases by surgery, and 1 case by interventional puncture), and 9 cases (36.0%) were suspected. The average age of onset was 40 years old. Most patients ( n=23, 92.0%) had abdominal pain along with emaciation to a various degree. Among them, 3 cases primarily presented as acute pancreatitis. Two cases were diagnosed after surgery for pancreatic masses. Eighteen cases were complicated with inflammatory bowel disease, including 16 cases with ulcerative colitis, one case with Crohn's disease, and one case with indeterminate colitis. All patients had typical imaging manifestations, including 13 cases (52.0%) with diffuse pancreatic enlargement, 12 cases (48.0%) with focal or multifocal pancreatic lesions, and 5 cases (20.0%) with simultaneous focal pancreatic masses and diffuse enlargement. All patients had normal serum IgG4 levels, anti-neutropil cytoplasmic antibodies (ANCA) positivity rate was 35.3% (6/17), and anti-nuclear antibody (ANA) positivity rate was 29.2% (7/24). Two surgical patients recovered well after surgery, and the other patients all achieved clinical and imaging relief after hormone therapy, and no recurrence was seen during follow-up. Compared with type 1 AIP, type 2 AIP had younger onset age, main manifestation as abdominal pain without jaundice, rare involvement with extra-pancreatic organs, the lesions mainly located in the intestine and normal IgG4 level with statistically significant differences. The recurrence rate of type 2 AIP was lower than that of type 1 AIP (0 vs 16%). Conclusions:Type 2 AIP has different clinical characteristics from type 1 AIP. Due to the lack of specific serum markers, the diagnosis is more difficult. It responds well to glucocorticoids and has a low recurrence rate.

Liver regenerative medicine can use functional liver cells to repair or replace damaged liver tissue and it is expected to be rapidly developed as an alternative treatment to liver transplantation. However, regenerative medicine requires cells with stable proliferation ability and liver cell characteristics. Liver organoids are derived from adult stem cells or pluripotent stem cells. They can be proliferated in large quantities and cultured for a long time in vitro, meanwhile maintain genetic stability, and simulate the structural and functional characteristics of organs in the body, providing a new strategy for liver regeneration. This article reviews liver organoids and their research progress in liver regenerative medicine, and discusses their application potential and existing limitations.

Objective To analyze the situation and study trend of large-scale nurses'health cohort studies based on Web of Science,to help design clinical guidelines and scientific research for nursing staff in China.Methods Articles of large nurses'health cohort studies published from 1993 to 2023 were retrieved from Web of Science(WOS)Core Collection.Citespace and Bibilometrix were used to perform the bibliometric analysis.Results 2882 studies were included in this study.Total volume of papers was enlarging by year.Clustering results showed that the main keywords could be divided into 3 categories:risks of women's health,risks of cardiovascular disease and reproducibility.Results of keywords burst showed that lifestyle,cardiovascular disease,women reproductive health and mental health were the highlights of studies in recent 5 years.Conclusion Research on large-scale nurse health cohorts holds significant scientific significance.It is recommended to establish a nationwide large-scale nurse health cohort as soon as possible.In the study,appropriate exposure factors should be selected,with reproductive health,mental health,and psychiatric disorders being the primary outcome measures,and chronic physical illnesses being the secondary outcome measures.By systematically describing the factors influencing the physical and mental health of nurses in China,we can better safeguard their well-being and promote the development of the nursing discipline.

Objective To analyze the epidemiological characteristics of new elderly malignant tumor cases in Tongren City from 2018 to 2022, so as to provide a theoretical basis for the prevention and control of elderly malignant tumor in this area. Methods A retrospective analysis of the epidemiological characteristics of cases aged 60 and above who were first diagnosed with malignant tumors by pathology in our hospital from 2018 to 2022 was conducted based on the International Classification of Diseases (ICD-10). Results The incidence rate of elderly malignant tumors in Tongren City increased from 123.83/100 000 in 2018 to 126.14/100 000 in 2022, and the incidence rate showed a trend of first rising and then declining. The top five tumors in incidence rate are lung cancer, rectal cancer, liver cancer, stomach cancer and cervical cancer. The tumor order has changed over the years except lung cancer, which was the first. Lung cancer was the main high incidence tumor among the elderly of all ages. With the increase of age, the number of bladder cancer patients increases significantly, and the number of colon cancer patients also shows an upward trend. The prevalence rate of lung cancer（χ²=16.032，P=0.014) , liver cancer（χ²=8.099，P=0.030) , bladder cancer（χ²=11.274 , P=0.018) , and gastric cancer（χ²=19.387 , P=0.011) in elderly people of different sexes was generally higher in men than in women, and the difference was statistically significant (P<0.05). Conclusion Lung cancer , rectal cancer and liver cancer, as the malignant tumors with high case composition and rapid increase in the elderly, can be the focus of early screening and prevention of malignant tumors in the elderly in Tongren City, and men should pay more attention.

Objectives:We aimed to compare the impact of dissection and re-entry(DR)recanalizing pattern with non-DR on the in-hospital results and prognostic outcomes of patients treated successfully by percutaneous coronary intervention(PCI)of chronic total occlusion(CTO)and examine the benefit of DR in CTO PCI. Methods:A total of 815 consecutive patients with CTO meeting the inclusion criteria in the Department of Cardiology of the First Affiliated Hospital of PLA Air Force Military Medical University from January 2018 to December 2020 were enrolled and divided into DR group(n=239)and non-DR group(n=576)according to whether DR recanalizing pattern was used in the procedure.The clinical characteristics,coronary angiographic characteristics,procedure results,and complications were collected,and the prognostic outcomes within one year after the procedure were observed.Propensity score matching by the clinical and coronary angiographic characteristics was performed and results were compared with 208 matched patients in each group.The endpoints were the major adverse cardiovascular events(MACE)consisting of all-cause death and myocardial infarction,clinically driven target vessel revascularization(TVR)one year after the procedure,and in-hospital outcomes. Results:The mean age of all patients was(60.9±10.9)years old,and 87.4%were male.As compared with the non-DR group,the proportion of blunt cap,ambiguous,calcification,angle＞45°,and diseased landing zone,as well as mean J-CTO score was higher in the DR group(all P＜0.05).The mean stent length and median procedure time were longer in the DR group,median guidewires and consumed contrast volume was also higher in the DR group(all P＜0.001).Incidence of in-hospital death,myocardial infarction,perforation,side branch loss,bleeding of BARC 3rd grade and above,and contrast-related impairment of renal function were similar between the two groups(all P＞0.05).However,peripheral vascular complications occurred more frequently in the DR group(P=0.007).One year after the procedure,the incidence of MACE(2.9%vs.2.4%,log-rank P=0.750)and clinically driven TVR(5.8%vs.3.9%,log-rank P=0.365)as well as all-cause death(2.9%vs.1.0%,log-rank P=0.154)and myocardial infarction(0.5%vs.1.9%,log-rank P=0.184)were similar between the two matched groups.Multivariate Cox regression analysis showed no significant association between DR and MACE(HR=1.129,95%CI:0.427-2.979,P=0.807)and TVR(HR=0.606,95%CI:0.213-1.722,P=0.347).LVEF≤40%(HR=2.775,95%CI:1.137-6.774,P=0.025)and elevated residual SYNTAX score(HR=1.089,95%CI:1.032-1.150,P=0.002)were risk factors for MACE,and diseased landing zone(HR=2.144,95%CI:1.019-4.513,P=0.045),rescued ADR(HR=3.479,95%CI:1.109-10.919,P=0.033),and prolonged procedure time(HR=1.007,95%CI:1.002-1.013,P=0.007)were risk factors for TVR. Conclusions:CTO lesion recanalized with PCI utilizing DR operation pattern was associated with more complex characteristics,more devices and time consumed,and longer stent length,while no significant association was observed between DR operation pattern and MACE and TVR one year after the procedure,as well as in-hospital complication..

Objective To observe the value of extracellular volume(ECV)and relative electron density(RED)based on dual-layer detector spectral CT(DLCT)for identifying colon cancer invasion into serous membrane.Methods Sixty-two patients with pathologically confirmed colon cancer with blurred pericolonic fat gap on CT images were retrospectively collected,including 18 cases of T4a stage tumors with serous membrane invasion and 44 cases of T2-T3 stage without serous membrane invasion.The arterial,venous and delayed phase DLCT images under 40 keV showing the largest diameter of colon cancers were analyzed.The iodine concentration(IC)and RED of the pericolonic fat around tumor-bearing and tumor-free intestines,as well as of the abdominal aorta or the common or external iliac artery were measured,while normalized IC(NIC)and difference of RED(REDdiff)of pericolonic fat around tumor-bearing and tumor-free intestines in each phase and ECV in delayed phase were calculated.The above parameters were compared between tumors with different stages,and for those with significant differences,the receiver operating characteristic curves were drawn,and the areas under the curve(AUC)were calculated to evaluate and compare the efficacies for identifying invasion of serous membrane in T4a stage colon cancer.Results Compared with T2-T3 stage colon cancers,T4a stage colon cancers were found more often occurred in patients aged ＜50 with higher proportion of lymph node metastases(both P＜0.05),also higher values of NIC and REDdiff on images in different phases,as well as ECV in delayed phase images(all P＜0.05).The AUC of arterial,venous and delayed phase NIC for differentiating T2-T3 and T4a stage colon cancers ranged from 0.868 to 0.902,while of REDdiff ranged from 0.848 to 0.903,all without significant difference(all P＞0.05).The AUC of delayed phase ECV was 0.948,not significant different with that of delayed phase NIC and REDdiff,arterial phase NIC nor venous phase REDdiff(all P＞0.05).Conclusion Based on DLCT,ECV and RED could be used to identifying serous membrane invasion of colon cancer when blurred pericolonic fat gaps were noticed.

Objective:To explore the predictive value of the prognostic nutritional index (PNI) in concurrently infected patients with acute-on-chronic liver failure (ACLF).Methods:220 cases with ACLF diagnosed and treated at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2016 were selected. Patients were divided into an infection and non-infection group according to whether they had co-infections during the course of the disease. Clinical data differences were compared between the two groups of patients. Binary logistic regression analysis was used to screen out influencing factors related to co-infection. The receiver operating characteristic curve was used to evaluate the predictive value of PNI for ACLF co-infection. The measurement data between groups were compared using the independent sample t-test and the Mann-Whitney U rank sum test. The enumeration data were analyzed using the Fisher exact probability test or the Pearson χ2 test. The Pearson method was performed for correlation analysis. The independent risk factors for liver failure associated with co-infection were analyzed by multivariate logistic analysis. Results:There were statistically significant differences in ascites, hepatorenal syndrome, PNI score, and albumin between the infection and the non-infection group ( P ?