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 explore the dose-response relationship between BMI and the prevalence of dyslipidemia using restricted cubic spline model.Methods Using data of Chronic Disease and Risk Factor Surveillance in Nanjing City from 2017 to 2018.A representative sample of 61 098 residents aged≥18 years was surveyed by face-to-face questionnaire survey,anthropometric measurements and laboratory examinations.A logistic regression model of complex sampling and restricted cubic spline model were used to analyze the dose-response relationship between BMI and the risk of dyslipidemia.Results Finally,60 283 subjects were included.Among them,there were 17 093 dyslipidemia patients with a standardized prevalence rate of 29.8%.After adjusting for confounding factors by multiple logistic regression,participants with overweight(OR=1.43,95%CI:1.36～1.49)and obesity(OR=1.97,95%CI:1.83～2.12)had a significantly higher risk of dyslipidemia compared to those with normal weight.The multiple restricted cubic spline model indicated a non-linear dose-response relationship between BMI and the risk of dyslipidemia in women,young,middle-aged and elderly population,and a linear dose-response relationship between BMI and the risk of dyslipidemia in men.Conclusion Weight control plays a very important role in the prevention of dyslipidemia.

Objective:To understand the epidemiological characteristics and trends of injury in older adults in Jiangsu Province from 2006 to 2022 and provide a scientific basis for developing prevention and control measures.Methods:The data on injury cases aged 60 and older were collected from 12 sentinel hospitals in Jiangsu Province during 2006-2022. The study analyzed the proportion of injury cases among the elderly in the overall population and calculated the annual percent change and average annual percent change (AAPC). A pairwise comparison between groups was performed, and the differences were judged according to the adjusted standardized residuals.Results:From 2006 to 2022, there were 218 426 injury cases among individuals aged 60 and older in Jiangsu Province, which accounted for an increasing proportion of injury cases within the entire population (AAPC=3.17%, P<0.001). The first five causes of elderly injury were falls (42.06%), road traffic injuries (20.20%), animal injuries (11.45%), knife/sharp injuries (9.43%), and blunt injuries (8.13%). From 2006 to 2022, the proportion of falls, animal injuries, and knife/sharp injuries among the elderly aged ≥60 showed an increasing trend, while the proportion of road traffic injuries and blunt injuries decreased (all P<0.001). The incidence of injury was highest in October, with a daily incidence peak between 8:00 and 10:00. Leisure activities (40.34%) were the major activity leading to injury. The injury occurred mainly at home (53.74%), and the injury intention was mainly unintentional (97.41%), all of which showed an increasing trend ( P<0.001). The injuries were mainly bruises (36.00%), and the most common injured positions of the body were low limbs (27.55%), all of which showed a decreasing trend ( P<0.001). About 69.80% of cases were slight, and 79.38% were discharged after treatment, which showed an increasing trend ( P<0.001). Conclusions:The injury data for individuals aged 60 and older in Jiangsu Province exhibited varying trends from 2006 to 2022. There was a noticeable increase in the proportion of elderly injury cases within the overall injury population, as well as an upward trend in falls, animal injuries, and knife/sharp injuries as leading causes of injury. It is imperative to actively develop prevention measures based on the epidemiological characteristics and evolving trends of elderly injuries in Jiangsu Province.

Objective:To predict the possible targets and signaling pathways of Jiangtang Xiaoke Granules in the treatment of diabetes mellitus (DM) using computer network pharmacology and molecular docking technology.Methods:The active components and targets of Jiangtang Xiaoke Granules were collected by ETCM; the targets of DM were searched from the databases of DisGeNET and GeneCards, and the intersections of the two were taken to draw a Venny diagram; String database was used for gene transformation and network interaction analysis; the network diagram was constructed with Cytoscape3.6.0; the predicted results were supported by molecular docking technology; GO and KEGG analysis was performed through Metascape database.Results:A total of 128 active components of Jiangtang Xiaoke Granules were screened, with 607 corresponding targets, 1 240 DM related targets, and 53 core targets. Molecular docking showed that the active components had good binding energy with the core targets. GO analysis yielded 46 functional items and KEGG analysis yielded 15 pathways.Conclusion:Jiangtang Xiaoke Granules regulate glucose homeostasis by participating in a variety of biological processes through multiple components, and multiple targets, including affecting lipids and atherosclerosis, Alzheimer disease, AMPK signaling pathway, Apelin signaling pathway, and glucagon signaling pathway.

Objective To observe the influence of the staining phenomenon after fluorescein sodium staining on eye irritation in normal rabbits.MethodsIn the experimental rabbit eye irritation test conducted with sodium chloride eye drops, Siwei Zhenceng Bingpeng eye drops, sodium hyaluronate eye drops, sodium cromoglycate eye drops, and compound aspartate eye drops (4 in each group, half male and half female), the left eyes of rabbits were administered normal saline (self-negative control) and the right eyes were administered the experimental medicine; the eyes were stained with 1% sodium fluorescein, and eye irritation was observed and scored using slit lamp microscope for 31 days. Morphological changes of corneal epithelial staining were recorded and the incidence of staining was calculated. After the observation, the eyeballs and Hasselblad glands were examined histopathologically, and the staining rate of the left eye was compared with that of the right eye which was administered the corresponding medicine.ResultsNeither eye had any irritation symptoms; the scores were 0, and the total incidences of corneal staining were 3% (left) and 1% (right), respectively. There was no significant difference between the two groups (P > 0.05). Corneal epithelial staining showed single-spot staining, scattered dot, localized, or large areas of fusion staining. No histopathological changes were found in the eyeballs or Hasselblad glands, and the results were evaluated as non-irritative.Conclusion The irregularity of corneal epithelial staining in rabbits did not influence the results of the ocular irritation test.

Objective:To investigate the association between dietary intake and physical activity category and their combined effects on all-cause and cause-specific mortality risk in patients with type 2 diabetes mellitus (T2DM).Methods:Between December 2013 and December 2021, a prospective cohort study was conducted on 19 863 T2DM patients in Changshu City, Qingjiangpu District (formerly Qinghe District), and Huai'an District, included in the national basic health service management. Information on deaths and underlying causes of death was obtained from the Jiangsu Provincial CDC and Prevention Death Surveillance System. Cox proportional hazards models were used to estimate the intensity of associations between dietary intake, physical activity, and their combined effects with all-cause and cause-specific mortality in patients with T2DM.Results:As of December 31, 2021, the research subjects had been followed up for 150 283 person-years, with a median follow-up time of 8.15 years. During the follow-up period, 3 293 people died, including 1 124 deaths from cardiovascular disease (CVD) and 875 deaths from cancer. Cox regression analysis showed that compared with the population of 0-1 recommended food group, those having more than five recommended food groups had a 19% lower risk of all-cause mortality [hazard ratio ( HR)=0.81, 95% CI: 0.70-0.94] and a 33% lower risk of all-cause mortality ( HR=0.67, 95% CI: 0.52-0.87). Compared with the T2DM population in the physical activity Q1 group, the risk of all-cause mortality, CVD mortality, and cancer mortality among the physical activity Q4 group reduced by 50% ( HR=0.50, 95% CI: 0.45-0.56), 50% ( HR=0.50, 95% CI: 0.41-0.61), and 27% ( HR=0.73, 95% CI: 0.60-0.88), respectively. The combined effect showed that compared with the population in the intake of food categories 0-2 and low physical activity groups, the risk of all-cause, CVD mortality, and cancer mortality in the intake of food categories 4-9 and high physical activity groups reduced by 55% ( HR=0.45, 95% CI: 0.38-0.53), 56% ( HR=0.44, 95% CI: 0.32-0.59), and 40% ( HR=0.60, 95% CI: 0.44-0.82), respectively. Conclusion:Type of dietary intake, physical activity, and their combined effects are associated with a reduced mortality risk in patients with T2DM.

Objective:To meet the individualized needs of residents in standardized residency training of cardiac intervention specialty for cardiac ultrasound teaching, to construct a bionic 3D printing model of ultrasound source, and to discuss its application value in ultrasound teaching and simulation exercises.Methods:Sixty residents majored in cardiovascular medicine receiving standardized residency training of ultrasound in ultrasound imaging department of Renmin Hospital of Wuhan University were randomized into experimental group and control group in average. The experimental group adopted ultrasound bionic 3D printing heart model combined with problem-based learning (PBL) teaching method, and the control group adopted traditional multimedia PPT combined with PBL teaching method. At the end of teaching activities, theoretical examination, operation assessment and questionnaire survey were conducted to evaluate and compare the teaching effect between the two groups. SPSS 21.0 software was performed for t test. Results:The theoretical examination scores of the experimental group and the control group were (81.4±8.2) points and (74.8±9.4) points, respectively, P=0.002, and the operation assessment scores were (89.1±5.6) points and (71.5±8.8) points, respectively, P<0.001. The questionnaire survey showed that the experimental group had better feedbacks than the control group in the aspects of mastery of heart anatomy knowledge, learning experience, learning interest, learning efficiency, understanding of interventional heart disease, clinical skills of interventional operation and overall satisfaction (all P<0.05). Conclusions:Ultrasound bionic 3D printing combined with PBL teaching method can help strengthen the mastery of cardiac anatomy knowledge, promote the learning experience of cardiac ultrasound and improve the skills of interventional operation. The teaching effect is significant and the students' satisfaction is high.

Objective:To explore the effect of systolic anterior motion (SAM) of mitral valves on the morphology and function of left ventricular outflow tract (LVOT) in patients with hypertrophic obstructive cardiomyopathy (HOCM) using computer fluid dynamics based on three-dimensional echocardiography with inverted grey values.Methods:A total of 40 patients with hypertrophic cardiomyopathy were divided into SAM group (24 cases) and non SAM group (16 cases) in Renmin Hospital of Wuhan University from April 2016 to October 2019. Two dimensional and three-dimensional echocardiographic data of the patients were collected. The LVOT morphological model was constructed based on the post-processing of three-dimensional echocardiography data, and the LVOT flow field model was constructed based on the time-volume curve of left ventricle. LVOT peak velocity was obtained to assess the agreement with echocardiography measurements. Area of LVOT, average velocity, flow rate and iso-surface area of vortex of different levels were obtained and compared between the two groups.Results:There was a good correlation between cardiac fluid model and echocardiographic measurement ( r=0.943, P<0.01). The Bland-Altman consistency interval was -75.0-111.3, and 92.5% of the points were within the consistency limit. Compared with non-SAM group patients, the peak velocity of LVOT increased, the area of LVOT decreased, the flow rate decreased and the area of vortex increased in SAM patients (all P<0.01). In the SAM group, in 16 patients the double orifice LVOT was observed due to the contact between mitral valve and septum, in 1 patient the single orifice LVOT structure was observed with contact between mitral value and septum, and in 7 patients, single orifice LVOT without contact between mitral value and septum. In SAM patients, compared with single orifice LVOT, patients with double orifice LVOT were observed with higher LVOT velocity, smaller LVOT area and higher vortex area with high level(all P<0.05). Conclusions:Accurate fluid models can be obtained using three-dimensional echocardiography with inverted grey values. In SAM patients, contact between mitral valve and septum leads to the formation of double orifice structure and the increase of vortex level in LVOT.

Objective:To evaluate the accuracy and application value of the left atrial appendage(LAA) occlusion simulation in dynamic fluid in vitro based on left atrial appendage models. Methods:The preoperative two/three-dimensional transesophageal echocardiography(2D/3D-TEE) images of 21 patients with atrial fibrillation undergoing percutaneous LAA occlusion were retrospectively analyzed. LAA models with different materials (silicone-hydrogel LAA models, silicone LAA models and Tangoplus LAA models) were obtained by 3D printing. After simulation evaluation set models in a dynamic fluid system to simulate the occlusion operation, the type of occluder was predicted, the correlation between them and the final occluder used in the operation was analyzed.According to 2D/3D-TEE monitoring in 21 patients, the compression ratio of occluders was measured and the residual leakage around occluders was observed. With the same type occluder as in surgery, the compression ratio of occluders and residual leakage around the occluders in the three LAA models were observed and compared with intraoperative measurements, the descriptive and correlation analyses were conducted.Results:The simulation score of silicone-hydrogel LAA models was higher than those of silicone LAA models and Tangoplus LAA models. The occluder size in silicone-hydrogel LAA models was more correlated to the size used in the operation( r=0.937, P<0.001) than silicone LAA models ( r=0.918, P<0.001) and Tangoplus LAA models ( r=0.895, P<0.001). With the same size of occluder, there was no significant difference between the compression ratio of the occluder in silicone-hydrogel LAA models and intraoperative ( P=0.908). In 21 patients, 7 cases of residual leakage of occluder were observed during operation, while 4 cases were observed in silicone-hydrogel LAA, 5 cases were observed in silicone LAA models and 5 cases in Tangoplus LAA models. Conclusions:Preoperative simulation system of left atrial appendage occlusion based on silica gel-hydrogel model is helpful for preoperative decision-making, simulation exercise and post-operative evaluation of percutaneous left atrial appendage occlusion.

Objective:The purpose of this study is to establish the trajectory of targeted grafting for facial fat compartment based on anatomical research, and then bring it to clinical practice.Methods:The boundary of fat compartment and the relationship of adjacent vessel and nerve were clarified through autopsy. The recommended injection points and trajectory for targeted fat grafting were established on the anatomical findings. Retrospective clinical data of facial rejuvenation of 46 patients through targeted fat grafting were collected from June 2017 to June 2019 in Shanghai Ninth People’s Hospital. The result of 3D scanning were analyzed to evaluate the survival rate of fat grafts.Results:There were subcutaneous superficial fat compartments in the frontal region, and there were both deep and superficial fat compartments in the temporal and middle face. According to the anatomical characteristics, a targeted fat grafting technique was established with the frontal hairline and the oral commissure corner mucosa as the entry points. In the clinical study, 46 patients were evaluated by 3D scanning 6 months after the last fat grafting. The amount of fat grafts in the temporal region was (17.84±8.47) ml and (11.2±2.44) ml was left after operation, and the survival rate was 63%. The amount of fat grafts in mid-face was (26.81±10.36) ml and (16.09±4.48) ml was left after operation, and the survival rate was 60%. Overall satisfaction rate of patients was 93% (43/46).Conclusions:Compartment-based targeted fat grafting is an accurate injection method, which meets the requirement of physiological augmentation. The trajectory of targeted fat grafting will further improve the efficacy and safety of injection.