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 compare the effects of different test meals on postprandial triglycerides and to optimize the standard meal composition and the blood sampling protocol for the oral fat tolerance test.Methods:This study is a prospective, open-label, randomized, cross-over trial. In March 2023, 36 volunteers were recruited in Hebei General Hospital. They underwent a health examination and oral glucose tolerance test. Twenty-six healthy volunteers(11 males and 15 females) were included in this study, with an average age of(39.08±4.56) years. Each volunteer received 75 g protein meal, 75 g fat meal, 700 kcal fixed-calorie high-fat mixed meal, and a high-fat mixed meal with energy adjusted based on 10 kcal/kg body weight. A one-week washout period of regular diet was applied before each trial. Blood was collected at fasting status and 1, 2, 3, 4, 5, and 6 hours after a meal to detect serum triglycerides, total cholesterol, low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), glucose, and insulin. The variations of postprandial metabolic indicators over time following the consumption of different test meals were analyzed. The disparities in postprandial metabolic responses between the two types of mixed meals were compared.Results:The protein meal, fat meal, fixed-calorie high-fat mixed meal, and adjusted-calorie high-fat mixed meal resulted in postprandial triglyceride increases of 22.45%, 115.40%, 77.14%, and 63.63%, and insulin increase of 560.43%, 85.69%, 554.18%, and 598.97%, respectively, and with reductions in total cholesterol, LDL-C, and HDL-C ranging from 5.64%-21.81%, respectively. The blood glucose changed slightly. Changes in metabolic indicators mainly occured within 4 hours. The comparison of the characteristics of postprandial triglycerides between the two high-fat mixed meals showed no statistically significant differences( P>0.05). Conclusion:A standardize protocol with a 700 kcal fixed-calorie high-fat mixed meal as test meal, and blood lipid levels measured at fasting and at 1, 2, 3, and 4 hours after consumption, can serve as an optimized approach for oral fat tolerance test.

Objective To evaluate the myocardial microcirculation function of patients with acute myocardial infarction(AMI)after treatment with myocardial contrast-enhanced ultrasound combined with albumin(ALB)and lipoprotein a[Lp(a)].Methods Ninety-six patients with AMI admitted to our hospital from January 2022 to September 2023 were selected.According to myocardial microcirculation function after treatment,they were divided into a normal function group(56 cases)and a dysfunction group(40 cases).major cardiovascular adverse events were compared between the two groups.major cardiovascular adverse events(MACE),the plateau peak intensity of myocardial contrast ultrasound parameters(A value),the rise rate of microbubble reperfusion(β value),myocardial blood flow(A value×β value),and serum ALB and Lp(a)levels after 48h of treatment were different,so as to determine the evaluation value of myocardial contrast ultrasound,ALB and Lp(a)on myocardial microcirculation function in AMI patients after treatment.Results In the dysfunction group,the parameters A,β,A×β,and serum ALB level,Lp(a)was higher than that in the normal function group(P＜0.05).A,β,A×β,ALB were positively correlated with cardiac function,and Lp(a)was negatively correlated with cardiac function(P＜0.05).CEUS combined with ALB and Lp(a)evaluated the efficacy of myocardial microcirculation in patients with AMI(P＜0.05).The incidence of MACE was higher in the functional group than in the normal functional group(P＜0.05).Conclusion Myocardial contrast-enhanced ultrasound can early evaluate the myocardial microcirculation function in patients with acute myocardial infarction after treatment,and combined with serum ALB and Lp(a),it can improve diagnostic efficacy.

Objective:To analyze the level of sodium and potassium intake and their association with blood pressure among people aged 18 to 75 years old in six provinces.Methods:From October to December 2018, participants aged 18 to 75 years were selected from Hebei, Hunan, Sichuan, Jiangxi, Qinghai and Heilongjiang provinces by using cluster random sampling method. Demographic characteristics and lifestyle information were collected by using questionnaire survey. Physical measurement and 24-hour urine collection were also conducted.Results:A total of 2 636 subjects were finally included in the analysis. The average urine sodium, potassium and sodium-to-potassium molar ratio were(4 438.4±1 822.8)mg/d, (1 566.2±646.3)mg/d, and 5.2±2.2, respectively. According to World Health Organization standards, 94.5% and 98.7% of the respondents had excessive sodium intake and insufficient potassium intake. After adjusting for related factors, each 1 000 mg increase in sodium excretion was associated with increased systolic blood pressure (1.65 mmHg, 95% CI: 1.07, 2.22) and diastolic blood pressure (0.53 mmHg, 95% CI: 0.21, 0.84), and each 1 000 mg increase in potassium excretion was associated with decreased systolic blood pressure (3.02 mmHg, 95% CI:-4.25, -1.80) and diastolic blood pressure (1.27 mmHg, 95% CI:-2.05, -0.48). Conclusion:The sodium intake in Chinese population remains excessive and potassium intake is insufficient. Sodium and potassium could be associated with blood pressure and the intervention of reducing sodium and supplementing potassium should be conducted in the corresponding population.

Objective:To analyze the level of sodium and potassium intake and their association with blood pressure among people aged 18 to 75 years old in six provinces.Methods:From October to December 2018, participants aged 18 to 75 years were selected from Hebei, Hunan, Sichuan, Jiangxi, Qinghai and Heilongjiang provinces by using cluster random sampling method. Demographic characteristics and lifestyle information were collected by using questionnaire survey. Physical measurement and 24-hour urine collection were also conducted.Results:A total of 2 636 subjects were finally included in the analysis. The average urine sodium, potassium and sodium-to-potassium molar ratio were(4 438.4±1 822.8)mg/d, (1 566.2±646.3)mg/d, and 5.2±2.2, respectively. According to World Health Organization standards, 94.5% and 98.7% of the respondents had excessive sodium intake and insufficient potassium intake. After adjusting for related factors, each 1 000 mg increase in sodium excretion was associated with increased systolic blood pressure (1.65 mmHg, 95% CI: 1.07, 2.22) and diastolic blood pressure (0.53 mmHg, 95% CI: 0.21, 0.84), and each 1 000 mg increase in potassium excretion was associated with decreased systolic blood pressure (3.02 mmHg, 95% CI:-4.25, -1.80) and diastolic blood pressure (1.27 mmHg, 95% CI:-2.05, -0.48). Conclusion:The sodium intake in Chinese population remains excessive and potassium intake is insufficient. Sodium and potassium could be associated with blood pressure and the intervention of reducing sodium and supplementing potassium should be conducted in the corresponding population.

Objective:To observe the clinical effect of pelvic floor ultrasound in the diagnosis and rehabilitation training of postpartum stress urinary incontinence(SUI).Methods:From May 2017 to May 2019, 200 SUI patients and 200 healthy pregnant women in the same period admitted to the First People's Hospital of Huzhou were selected in this study.All the subjects were tested by perineum and pelvic floor ultrasound, and the patients with SUI were instructed to carry out pelvic floor muscle rehabilitation training, the level of rehabilitation training effect was evaluated, and to statistically analyze the difference of pelvic floor ultrasound parameters between the patients with SUI and the healthy women, and the patients with different levels of efficacy.Results:The results of pelvic floor ultrasound in SUI patients were significantly higher than those in healthy women( t=6.536-14.925, all P<0.05). The rate of urinary leakage in SUI patients [88.50%(177/200)] was significantly higher than that in healthy women [10.50%(21/200)](χ 2=243.384, P<0.05). The total effective rate of rehabilitation training was 79.50%(159/200). The bladder neck moving distance, urethra rotation angle, posterior angle of bladder urethra in resting state and posterior angle of bladder urethra in Valsalva state in SUI patients with ineffective rehabilitation training were significantly higher than those in SUI patients with general effective rehabilitation training( t=4.662-12.537, all P<0.05). The formation rate of urethra infundibulum in SUI patients with ineffective rehabilitation training [70.73%(29/41)] was significantly higher than that in SUI patients with effective rehabilitation training [19.50%(31/159)](χ 2=40.744, P<0.05). Conclusion:The rehabilitation training of discoid muscles can effectively relieve the related clinical symptoms of postnatal SUI patients.The detection of pelvic ultrasound has a certain clinical value in the diagnosis of postpartum SUI and evaluation of rehabilitation training effect.

Objective To explore the value of contrast-enhanced ultrasound (CEUS) and intraluminal contrast in the differential diagnosis of postmenopausal endometrial benign and malignant lesions.Methods The ultrasound data of 90 patients with postmenopausal endometrial lesions diagnosed in our hospital between March 2016 and March 2018 were retrospectively analyzed.According to pathological findings,they were divided into benign group (55 cases) and malignant group (35 cases).The endometrial thickness of endovascular contrast,rise time (RT),time to peak (TTP),base intensity (BI),and peak intensity (PI) of CEUS in two groups were compared.Receiver operating characteristic curves (ROC) were used to compare the efficacy of different ultrasound parameters in benign and malignant endometrial by using pathology diagnosis as "gold standard".Results The endometrial thickness and PI were significantly higher in the malignant group than those in the benign group (P ＜ 0.05),while the RT and TTP were significantly lower than benign group (P ＜ 0.05),with no statistical difference in BI (P ＞ 0.05).The ROC curve showed that PI has the highest area under curve (AUC) in the differential diagnosis of benign and malignant endometrial lesions (AUC =0.983),followed by RT and TTP (AUC =0.889,0.872),and intimal thickness (AUC =0.766).AUC of PI was significantly higher than RT,TTP and intimal thickness (P ＜ 0.05),and the best cut-off point for PI ≥20.23 dB.The sensitivity of PI,RT,and TTP in differentiating benign and malignant endometrial lesions was significantly higher than that in intimal thickness (P ＜ 0.05),whereas the specificity and positive likelihood ratio (+ LR) of PI were significantly higher than those of RT,TTP,and intimal thickness (P ＜ 0.05).Conclusions Compared with intracavitary ultrasound,CEUS has better diagnostic value in differentiating benign and malignant endometrial tumors.Among them,the diagnostic sensitivity and specificity of PI≥20.23 dB are higher.

Objective: To evaluate the effect of lifestyle intervention among high risk group of chronic diseases in Shenzhen Futian district. Methods: 12 out of 115 communities were randomly selected in Futian district of Shenzhen city from October to November, 2013, and 1 923 cases were screened by multiple ways as high risk groups of chronic diseases. High risk groups of chronic diseases were divided into intervention group (1 338 cases, from five residential communities and three villages within city) and control group (585 cases, from four residential communities). The intervention group received group based health education activities as well as lifestyle intervention. The intervention group was provided with health management which was mainly lifestyle intervention. No intervention was implemented in the control group. All participants were followed up over two years. 1 563 participants (1 002 in intervention group and 561 in control group) were followed up from October to November, 2015. The changes of lifestyle related outcome indicators were analyzed to examine the effect of intervention. Results: In the intervention group, 21.8% (219 persons) in high risk groups of chronic diseases became healthy individuals and 15.2% (152 persons) became patients with chronic diseases. In the control group, 9.6% (54 persons) in high risk groups of chronic diseases became healthy individuals and 20.5% (115 persons) became patients with chronic diseases. The outcome of the intervention group was better than that of the control group and the difference was statistically significant (χ²=-5.67, P<0.001). The proportion of people who knew how to correctly use of oil control pot in the intervention group increased from 61.00% (61/100) to 80.00% (280/350). The proportion of people who took oil control measures in the intervention group increased from 36.43% (365/1 002) to 56.99%(571/1 002). The changes in the intervention group were statistically different (P<0.001), but there was no statistical difference in the control group over the years (P>0.05). The proportion of people who knew how to correctly use of the salt restriction spoon increased from 81.95% (109/133) to 97.99% (342/349). The proportion of people who took salt control measures increased from 45.61% (457/1 002) to 62.67% (628/1 002) in the intervention group. The changes in the intervention group were statistically different (P<0.001). There was no statistical difference in the control group over the years (P>0.05). Conclusion The proportion of people who adopted healthy lifestyles has increased after 2 years intervention and the lifestyle intervention demonstrated good effect.

Objective To evaluate the diagnostic efficacy of narrow band imaging (NBI) international colorectal endoscopic (NICE) classification in distinguishing neoplastic from non-neoplastic colorectal polyps during routine clinical practice. Methods A total of 224 lesions detected by white light colonoscopy by non-expert endoscopists were collected in this retrospective study. Each lesion was assessed by NBI and classified by NICE classification. The results were compared with pathological findings from endoscopic or surgical resected specimen. Results Among these 224 polyps, there were 59 of type 1, 159 of type 2 and 6 of type 3 according to NICE classification. There were 58 non-tumorous and 166 tumorous polyps according to pathological diagnosis. The total diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of NICE classification for colorectal tumor were 91. 6%, 77. 6%, 92. 1%,76. 3%and 87. 9%, respectively.Diagnostic sensitivity and accuracy in big (＞10 mm in diameter), small (＞5-10 mm in diameter) and mini (≤5 mm in diameter) polyp groups were 100. 0%, 97. 0% and 80. 9%, as well as 95. 7%, 87. 8%, and 83. 3%, respectively. Diagnostic accuracy showed a decreasing tendency on polyp size, without significant difference between the three groups ( P＝0. 694). Conclusion NICE classification with non-magnified NBI is effective in distinguishing neoplastic and non-neoplastic colorectal polyps by non-expert endoscopists and is potentially worth popularizing for routine clinical practice.

OBJECTIVE:To compare clinical efficacy and safety of intravenous dripping of methotrexate and uterine arterial perfusion embolization combined with complete curettage of uterine cavity (CCUC) in the treatment of cesarean scar pregnancy (CSP).METHODS:A total of 90 CSP patients were randomly divided into group A and B,with 45 cases in each group.Group A was given Methotrexate (MTX) injection 50 mg/m2 intravenously before CCUC.Group B received Seldinger catheterization in supine position before CCUC,and was given sequential infusion of MTX injection 50 mg/m2 and gelatin sponge particles into the uterine artery;the catheter was removed after satisfactory embolization by imaging examination.The levels of β-HCG of 2 groups were reexamined every 24 h,and CCUC was performed when serum β-HCG level was below 1 000 mU/mL.Perioperative bleeding volume,postoperative bleeding volume,the time of blood β-HCG returning to normal,the time of menstruation returning to normal,hospitalization time as well as the lesion diameters,the levels of blood β-HCG,the occurrence of compliance and ADR before and after treatment were compared between 2 groups.RESULTS:The intraoperative bleeding amount and postoperative bleeding amount of group B were significantly lower than those of group A,while the time of blood β-HCG returning to normal,the time of menstruation returning to normal and hospitalization time were significantly shorter than group A,and the incidence of total compliance was significantly lower than group A,with statistical significance (P＜0.05).Before medication,there was no statistical significance in lesion diameters between 2 groups (P＞0.05).Before CCUA,the lesion diameters of 2 groups were significantly smaller than before medication,and the group B was significantly smaller than group A,with statistical significance (P＜0.05).Before medication,there was no statistical significance in blood β-HCG levels between 2 groups (P＞0.05).Before and after CCUC,blood ββHCG levels of 2 groups were significantly lower than before medication,and the group B was significantly lower than group A,with statistical significance (P＜0.05).There was no statistical significance in the incidence of ADR between 2 groups (P＞0.05).CONCLUSIONS:Compared with methotrexate by intravenous drip,methotrexat by uterine artery embolization combined with CCUC for CSP can effectively reduce intraoperative bleeding amount,promote the decrease of blood β-HCG and menstrual recovery,and contribute to the reduction of complication risk with good safety.