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.

Objective:To investigate the clinical value of multiparameteric quantitative ultrasound combined with a non-invasive prediction model for assessing high-risk steatohepatitis.Methods:One hundred and ninety-four cases with metabolic-associated fatty liver disease (MAFLD) who underwent liver biopsy in Huashan Hospital, Fudan University, from June 2021 to September 2022 were selected. Shear wave elastography (SWE), shear wave dispersion (SWD) imaging, and attenuation imaging (ATI) examinations were conducted in all patients before biopsy. High-risk steatohepatitis was defined as a total activity score of ≥4 in patients with steatohepatitis, hepatocellular ballooning, and liver lobular inflammation based on pathological hepatic steatosis, inflammatory activity, and fibrosis scoring system (SAF), and fibrosis stage≥F2. Binary logistic regression analysis was used to identify the factors influencing high-risk steatohepatitis. A predictive model for diagnosing high-risk steatohepatitis was constructed using R language. The DeLong test was used to compare the area under the curve between groups. Measurement data was compared between groups using the t-test or rank-sum test, and count data were compared between groups using the χ2 test. Results:There were 46 cases (23.7%) with high-risk steatohepatitis. The quantitative ultrasound parameters included elastic modulus ( OR=2.958, 95% CI: 1.889-4.883, P<0.001), dispersion coefficient ( OR=1.786, 95% CI: 1.424-2.292, P<0.001) and attenuation coefficient ( OR=42.642, 95% CI: 3.463-640.451, P=0.004). Serological indexes of fasting blood glucose ( OR=1.196, 95% CI: 1.048-1.392, P=0.011), alanine aminotransferase ( OR=1.012, 95% CI: 1.006-1.019, P<0.001), aspartate aminotransferase ( OR=1.027, 95% CI: 1.014-1.042, P<0.001), γ-glutamyl transferase ( OR=1.008, 95% CI: 1.001-1.017, P=0.041) and HDL cholesterol ( OR=0.087, 95% CI: 0.016-0.404, P=0.003) were the factors influencing its progression. The AUCs of elastic modulus, dispersion coefficient, attenuation coefficient, multiparametric ultrasound model, serological index model, and ultrasound combined with serology model for the diagnosis of high-risk steatohepatitis were 0.764, 0.758, 0.634, 0.786, 0.773 and 0.825, respectively. The results of the DeLong test showed that the ultrasound combined with the serological model was significantly better than the serological index model and the elastic modulus, dispersion coefficient, and attenuation coefficient alone ( P=0.024, 0.027, 0.038 and <0.001). Conclusion:The combination of multiparametric quantitative ultrasound is helpful for the non-invasive diagnosis of high-risk steatohepatitis and possesses great clinical significance.

Objective To investigate the predictive value of inflammatory cells and clinical features in the prognosis of immune checkpoint inhibitors (ICIs) treating non-small cell lung cancer (NSCLC).Methods The data of 163 cases of stage Ⅲ and Ⅳ NSCLC patients treated with the ICIs in this hospital from January 1,2017 to December 31,2022 were collected.The CT examination was conducted after 6-8 weeks treatment.The pa-tients were divided into the objective remission group[complete remission (CR)+partial remission (PR)]and non-objective remission group[stable disease (SD)+progressed disease (PD)],disease control group (CR+PR+SD) and non-disease control group (PD),persistent clinical benefit group (DCB) and non-DCB group.The differences in clinical features and inflammatory cells indicators were compared among the differ-ent groups.The receiver operating characteristic (ROC) curve was adopted to evaluate the predictive efficiency of the inflammatory cells indicators for DCB.The influencing factors analysis of progression free survival (PFS) time and overall survival (OS) time adopted the Cox regression analysis.Results The lymphocyte count (ALC) in the disease control group was higher than that in the non-disease control group.The neutro-phil to lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR) and mononuclear lymphocyte ratio (MLR) were lower than those in the non-disease control group.The proportions of squamous cell carcinoma,stage Ⅲ,ECOG score 0-1 point,adverse reactions in the DCB group were higher than those in the non-DCB group (P<0.05),the PLT count,NLR,PLR and MLR were lower than those in the non-DCB group (P<0.05). The ROC curve analysis results showed that PLT,NLR,PLR and MLR could serve as the indicators for pre-dicting DCB,the area under of ROC curve (AUC) was 0.633,0.602,0.635 and 0.604 respectively,the opti-mal cut off values were 187×109/L (P=0.004),5.0 (P=0.026),235 (P=0.003) and 0.35 (P=0.024) re-spectively.The multivariate Cox regression analysis showed that non-squamous carcinoma including adenocar-cinoma (HR=1.565,95％CI:1.057-2.316) and other pathologic types (HR=2.285,95％CI:1.326-3.936),ECOG score 2-3 points (HR=2.375,95％CI:1.652-3.415),AMC≥0.65×109/L (HR=1.847,95％CI:1.160-2.938) and PLR≥235 (HR=1.557,95％CI:1.016-2.386) were the independent risk factors for short PFS.The ECOG score 2-3 points (HR=4.615,95％CI:2.882-7.391),AMC≥0.65×109/L (HR=5.161,95％CI:2.984-8.925) and PLR ≥235 (HR=1.732,95％CI:1.059-2.833) were the independent risk fac-tors for short OS (P<0.05),and having adverse reactions (HR=0.472,95％CI:0.294-0.757) was the independ-ent protective factor for short OS (P<0.05).Conclusion Lower PLT,AMC,NLR,MLR and PLR,higher ALC,squamous cell carcinoma,TNM stage Ⅲ,ECOG score 0-1 point and immunotherapy related adverse reactions could prompt that the prognosis is good in ICIs treating advanced NSCLC.PLT,NLR,PLR and MLR could serve as the indicators for predicting DCB.

Objective:To comprehensively and systematically retrieve domestic and international research on nurse-initiated protocolized weaning in adult mechanically ventilated patients, clarify its outcome indicators and effectiveness in clinical practice, and identify influencing factors in its implementation.Methods:Employing the scoping review methodology of Arksey and O'Malley, databases in both English and Chinese were systematically searched. Literature was selected based on inclusion and exclusion criteria, with two researchers independently screening, organizing, and analyzing the articles.Results:Eighteen publications were included: seven interventional studies, four qualitative studies, two cross-sectional studies, two on instrument development, and three reviews. Nurse-initiated protocolized weaning was found to be safe and effective, with common clinical outcome indicators including mechanical ventilation duration, weaning time, and ICU length of stay. Significant barriers included the professional knowledge level of nurses, team cooperation, nurses' personal characteristics, and the healthcare providers' underestimation of patients' clinical symptoms. Continuous care, patient involvement, a supportive nursing culture, and recognition of the nurse's role were facilitators of this treatment.Conclusions:Future research efforts should standardize and refine the intervention measures of nurse-initiated protocolized weaning and conduct large-sample, high-quality studies to provide references for the implementation of nurse-initiated protocolized weaning in China.

Objective To observe the optimal target areas for shear wave velocity(SWV)evaluation on stages of chronic kidney disease(CKD)in different sides(left,right),different parts(upper pole,middle part and lower pole)and different tissue(renal cortex,renal medulla,renal sinus)of kidney.Methods Sixty-five CKD patients(130 kidneys)were retrospectively collected.SWV were compared between different sides,among different parts and tissue of kidney.The optimal regions for evaluating CKD stages were screened.Results No significant difference of SWV was found between left and right kidneys in same parts for same tissue(all P＞0.05),while significant differences of SWV of the same tissue were noticed among upper pole,middle part and lower part of kidney on the same side(all P＜0.05),i.e at upper pole＞at middle part＞at lower pole.Significant differences of SWV were also observed among renal cortex,medulla and sinus of kidney in the same side and parts(all P＜0.05),and the sinus had the highest SWV.Intraclass correlation coefficient analysis showed that the repeatability of the measurements of SWV was the best at the middle part of kidney.Besides,significant differences of SWV were found between renal cortex and medulla at the middle part of kidney among patients with stages 1,2,3 and 4-5 CKD(all P＜0.05),while the highest SWV were observed in patients with 4-5 stage CKD(all P＜0.05).SWV of renal cortex and medulla at middle part were positively correlated with CKD stages(both P＜0.01),the area under the curve of them for evaluating stage of CKD was 0.802 and 0.774,respectively.Conclusion The optimal target areas for SWV evaluation on stages of CKD were renal cortex and medulla at middle part of kidney.

Standardization is the universal language of the world, and standardization of traditional Chinese medicine (TCM) is essential for its communication in China and globally. However, the principles and methods of TCM acupuncture standardization have been unclear and inadequate in the early stages. Based on an investigative approach to understanding the current status, identifying problems, and finding solutions, our team has established basic principles of TCM acupuncture that embody Chinese wisdom, evaluated the international strategic environment systematically, proposed the principle of “importance of harmony and exercise of impartiality”, and established basic working principles. A series of methods for TCM acupuncture standard development and evaluation have been constructed, including general standards for the revision of TCM acupuncture standards, the first TCM acupuncture clinical research management specification, a shared full chain technology platform, a data center, and an evaluation research base for TCM acupuncture clinical research. Evaluation criteria for ancient literature and expert experience, a recommendation method for the “three main and three auxiliaries” TCM guideline for prevention were established, and quantifiable assessment methods of TCM standard applicability were proposed. These findings provide methodological guidance for TCM acupuncture standardization.

Objective To analyze the differences in the incidence of malignant tumors among urban and rural residents in Shenyang from 2013 to 2018. Methods From 2013 to 2018, the incidence data of malignant tumors of residents with household registration from national cancer surveillance sites in Shenyang urban area and rural Kangping and Faku counties were extracted. Crude incidence rate, age-standardized rate (standardized rate by Chinese population, standardized rate by world population), age specific incidence rate, cumulative incidence rate (0-74 years old), and truncated incidence rate (35-64 years old) were respectively calculated. SPSS23.0 software was used to carry out chi square test for the incidence of disease in urban and rural areas and in different age groups. Joinpoint 3.5.3 software was used to analyze the incidence trend in urban and rural areas. Results From 2013 to 2018, the age-standardized rate of cancer incidence by Chinese population（2000）and the cumulative rate of 0-74 years old in urban residents of Shenyang City were 199.85/105 and 22.21%, respectively, which were higher than those in rural residents, 172.84/105 and 19.85%, respectively. The incidence rate of cancer in males and females in urban area was higher than that in rural areas (χ²=262.47，χ²=103.83, P<0.05). The incidence rates in urban males and females and in rural females all showed an increasing trend in the past 6 years (APC=3.06%, APC=4.03%，APC=3.28% , P<0.05). The top five malignant tumors of urban males were lung cancer, colorectal cancer, liver cancer, gastric cancer and bladder cancer, while the top five malignant tumors of rural males were lung cancer, esophageal cancer, liver cancer, gastric cancer and colorectal cancer, respectively. The top five malignant tumors of urban women were breast cancer, lung cancer, colorectal cancer, thyroid cancer and cervical cancer, while the malignant tumors of rural women were lung cancer, breast cancer, colorectal cancer, cervical cancer and liver cancer, respectively. Conclusion From 2013 to 2018, the incidence of malignant tumor in urban residents in Shenyang is higher than that in rural areas. The incidence rates of urban males and females and rural females have showed an upward trend year by year in the past 6 years. There is a large difference in the order of tumor incidence between urban and rural men and women.

Objective:To explore the application of venetoclax in transplantation of patients with refractory acute myeloid leukemia (AML).Methods:The diagnosis and treatment process of a patient with refractory AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) under venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen after induction therapy failure in the First Affiliated Hospital of Soochow University in March 2020 were retrospectively analyzed.Results:The patient was a 28-year-old female who was diagnosed with refractory AML. The patient was initially given induction chemotherapy with IA (idarubicin+cytarabine) (3+7) regimen, but the disease did not relieve, then the induction chemotherapy with CLAG (cladribine+cytarabine+granulocyte colony stimulating factor) regimen was given, but the disease still did not relieve. After chemotherapy with venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen, salvage haploid allo-HSCT was performed. Re-examination of bone marrow showed remission, and implantation was successful. The patient was followed up for 100 days and had sustained remission, and no transplantation complications occurred.Conclusion:For refractory AML patients who have failed primary induction therapy, the use of venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen can be used as a preferred solution for salvage allo-HSCT.

Objective:To explore the diagnostic value of synthetic magnetic resonance imaging (syMRI) quantitative parameters for benign and malignant breast lesions.Methods:From September 2018 to March 2019, a total of 43 cases of breast lesions which were confirmed by surgery and pathology in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled in this study. All patients underwent syMRI sequence scans before and after enhancement except for conventional T2WI, DWI, and enhancement scans. GE AW4.7 workstation was used to generate syMRI parameter maps (T1, T2, proton density mappings), and ITK-SNAP software was used to delineate the volume of interest. The T1, T2, PD values before and after dynamic contrast enhanced (DCE) were obtained, and the change values of each parameter were calculated. Meanwhile, the apparent diffusion coefficient (ADC) and time intensity curve (TIC) of the lesions were measured. The differences of each parameter value were compared between benign and malignant breast lesions, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of each parameter.Results:Among the 43 enrolled cases, 13 were benign and 30 were malignant. Among the syMRI parameters, the pre-enhancement parameters including T1pre (median 1 663.07 ms), T2pre (median 103.33 ms), post-enhancement parameters ΔT1 (median 1 022.68 ms) and ΔT2 (median 27.67 ms) of benign group, significantly higher than those of the malignant group (the medians were 1 141.74, 92.53, 664.95, and 16.19 ms, respectively, P<0.05). The ADC value of the benign group (median 1.66×10 -3mm 2/s) was significantly higher than that of the malignant group (median 1.00×10 -3mm 2/s, P<0.05). The benign group included 6 cases of TIC curve type Ⅰ, 5 cases of type Ⅱ, and 2 cases of type Ⅲ. The malignant group included 2 cases of TIC curve type Ⅰ, 17 cases of type Ⅱ, and 11 cases of type Ⅲ. The difference between the two groups was statistically significant ( P<0.05). The area under the ROC curve (AUC) of T1pre before DCE was 0.869, higher than 0.806 of ADC and 0.697 of TIC. When the best cut-off value of 1 282.94 ms was chosen, the sensitivity and specificity of diagnosis were 76.9% and 93.3%, respectively. The combination of T1pre and T2pre can further improve the diagnostic performance (AUC=0.908). Conclusions:Among the syMRI quantitative parameters, T1pre, T2pre, ΔT1 and ΔT2 have good value for the differential diagnosis of benign and malignant breast lesions. T1pre has the best diagnostic performance, and the combination of T1pre and T2pre can further improve the diagnostic performance.

Objective:To explore the diagnostic value of synthetic magnetic resonance imaging (syMRI) quantitative parameters for benign and malignant breast lesions.Methods:From September 2018 to March 2019, a total of 43 cases of breast lesions which were confirmed by surgery and pathology in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled in this study. All patients underwent syMRI sequence scans before and after enhancement except for conventional T2WI, DWI, and enhancement scans. GE AW4.7 workstation was used to generate syMRI parameter maps (T1, T2, proton density mappings), and ITK-SNAP software was used to delineate the volume of interest. The T1, T2, PD values before and after dynamic contrast enhanced (DCE) were obtained, and the change values of each parameter were calculated. Meanwhile, the apparent diffusion coefficient (ADC) and time intensity curve (TIC) of the lesions were measured. The differences of each parameter value were compared between benign and malignant breast lesions, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of each parameter.Results:Among the 43 enrolled cases, 13 were benign and 30 were malignant. Among the syMRI parameters, the pre-enhancement parameters including T1pre (median 1 663.07 ms), T2pre (median 103.33 ms), post-enhancement parameters ΔT1 (median 1 022.68 ms) and ΔT2 (median 27.67 ms) of benign group, significantly higher than those of the malignant group (the medians were 1 141.74, 92.53, 664.95, and 16.19 ms, respectively, P<0.05). The ADC value of the benign group (median 1.66×10 -3mm 2/s) was significantly higher than that of the malignant group (median 1.00×10 -3mm 2/s, P<0.05). The benign group included 6 cases of TIC curve type Ⅰ, 5 cases of type Ⅱ, and 2 cases of type Ⅲ. The malignant group included 2 cases of TIC curve type Ⅰ, 17 cases of type Ⅱ, and 11 cases of type Ⅲ. The difference between the two groups was statistically significant ( P<0.05). The area under the ROC curve (AUC) of T1pre before DCE was 0.869, higher than 0.806 of ADC and 0.697 of TIC. When the best cut-off value of 1 282.94 ms was chosen, the sensitivity and specificity of diagnosis were 76.9% and 93.3%, respectively. The combination of T1pre and T2pre can further improve the diagnostic performance (AUC=0.908). Conclusions:Among the syMRI quantitative parameters, T1pre, T2pre, ΔT1 and ΔT2 have good value for the differential diagnosis of benign and malignant breast lesions. T1pre has the best diagnostic performance, and the combination of T1pre and T2pre can further improve the diagnostic performance.