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 effect of "Internet plus" exercise prescription intervention on upper limb dysfunction and quality of life of breast cancer patients at home after surgery, so as to provide reference for health management of breast cancer patients after surgery.Methods:Adopting a prospective randomized controlled trial research method. From November 2021 to January 2023, 124 breast cancer patients in the breast and thyroid surgery department of Xiang′an Hospital Affiliated to Xiamen University were selected for the study. According to the random number table method, they were randomly divided into an intervention group (62 cases) and a control group (62 cases). The control group patients were given routine training, and the intervention group patients received routine training in the first four weeks after operation, and "Internet plus" exercise prescription intervention in the fifth week after operation. The upper limb dysfunction, quality of life before and after the intervention and motor compliance after the intervention between the two groups were compared.Results:A total of 117 patients were ultimately included, and they were all female, with 58 patients in the intervention group aged (51.01 ± 9.77) years old and 59 patients in the control group aged (51.47 ± 9.85) years old. There was no statistically significant difference in upper limb dysfunction and quality of life between the two groups of patients before intervention ( P>0.05). After the intervention, the degree of upper limb dysfunction in the intervention group was (63.55 ± 7.02) points, which were lower than that in the control group (67.13 ± 7.25) points, and the difference was statistically significant ( t = 2.71, P<0.01). After the intervention, the total score of quality of life and the scores of physiological status, social/family status, emotional status, functional status and additional attention of breast cancer patients in the intervention group were (115.27 ± 17.35), (22.65 ± 4.53), (22.79 ± 4.36), (20.96 ± 3.95), (19.56 ± 4.22), (29.31 ± 5.24) points, which were higher than those in the control group (104.28 ± 17.04), (20.57 ± 4.48), (20.85 ± 4.23), (18.75 ± 4.04), (17.18 ± 4.06), (26.93 ± 5.21) points, the differences were statistically significant ( t values were 2.44-3.46, all P<0.05). In terms of exercise compliance of breast cancer patients in the intervention group, the aerobic exercise completion rate was 91.38% (53/58), muscle strength training completion rate was 77.59% (45/58), stretching exercise completion rate was 86.21% (50/58), exercise frequency was (3.96 ± 1.13) times/week, exercise duration was (29.51 ± 7.64) min/time, which was superior to 77.97% (46/59), 57.63% (34/59), 69.49% (41/59), (3.38 ± 0.94) times/week, (23.96 ± 7.33) min/time in the control group, the differences were statistically significant ( χ2 = 4.04, 5.31, 4.73, t = 3.02, 4.01, all P<0.05). Conclusions:"Internet plus" exercise prescription intervention has the characteristics of convenience, intuition and strong operability, which is conducive to improving the upper limb dysfunction, quality of life and exercise compliance of breast cancer patients at home after surgery. It is recommended to be popularized and applied clinically.

Objective To analyze the composition of the aqueous extract of Polygonatum Cyrtonema Hua(PCHE)and evaluate its antitumor activity in vitro and in vivo.Our aim is to provide a theoretical basis for the further development and utilization of Polygonatum Cyrtonema Hua.Methods(1)PCHE was prepared by aqueous extraction,and the chemical composition of PCHE was analyzed by UPLC-Q-TOF/MS and phenol-sulfuric acid method.The inhibitory activity on tumor cells proliferation of PCHE was detected by CCK-8 assay.Cell cycle and apoptosis were detected by flow cytometry,and the expression of apoptosis-related proteins Bcl-2 and Bax was detected by Western Blot.The inhibitory activity of PCHE-containing serum on cell proliferation was detected.(2)A B16 tumor-bearing mice model was constructed and model mice were randomly divided into the model group(saline),the positive drug group(CTX:50 mg·kg-1),and PCHE low-,medium-,and high-dose groups(55.9,111.8,223.6 mg·kg-1),and treated by gavage for 7 days.Changes in body weight and tumor volume of mice were observed during the treatment period.The mice were executed after the treatment,and the histopathological changes of heart,liver,spleen,lung,kidney and tumor were observed by hematoxylin-eosin(HE)staining.The protein expression of Bcl-2 and Bax in tumor tissues was detected by immunohistochemistry(IHC).Results The polysaccharide content of PCHE reached(10.07±1.3)%,and the flavonoid content was(0.044±0.004)%,and thirty-nine components were detected by UPLC-Q-TOF/MS,which contained antitumor components such as flavonoids(baicalein,quercetin,luteolin and rutin),organic acids(ferulic acid)and polyphenols(gallic acid),etc.PCHE exhibited the inhibitory effects on Hela,A549,4T1,B16,MFC and HepG2 cells,among which the inhibitory effect on B16 cells was the most significant(P＜0.001),and PCHE induced cell cycle arrest at G0/G1 phase in B16 cells(P＜0.001).The results of double-staining flow cytometry and Western Blot showed that PCHE significantly promoted apoptosis of B16 cells,decreased the expression of Bcl-2,and promoted the expression of Bax(P＜0.01,P＜0.001).and PCHE constituents absorbed into blood also had an inhibitory effect on B16 cells(P＜0.001).In addition,the results of in vivo activity assay showed that different doses of PCHE could inhibit tumor growth,induce tumor cell necrosis,reduce Bcl-2 expression,and increase Bax expression compared with the model group.Conclusion The ingredients in PCHE are abundant.It contains a variety of antitumor active ingredients,which can inhibit tumor growth,induce tumor cell apoptosis,show strong anti-tumor effects and be worthy of in-depth study.

Objective:To evaluate the accuracy of ultrasound measurement of airway parameters in predicting difficult mask ventilation (DMV).Methods:Ninety-six patients, aged 18-90 yr, with body mass index of 16-39 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective endotracheal intubation under general anesthesia, were included in this study. Clinical airway evaluation was performed at 1 day before surgery, and modified Mallampati classification, thyromental distance and rating of the upper lip bite test were recorded. At 30 min before anesthesia induction, mandibular condylar motion, tongue longitudinal cross-sectional area and transverse diameter of tongue were measured by ultrasound, and the tongue volume (product of tongue longitudinal cross-sectional area and transverse diameter of tongue) was calculated. Mask ventilation was performed after induction of anesthesia, mask ventilation difficulty grade ≥Ⅲ was defined as DMV, the patients were divided into 2 groups according to whether DMV occurred: non-DMV group (NDMV group) and DMV group. Correlations between the clinical airway evaluation indexes and ultrasonic airway parameters with statistically significant differences between groups and DMV were assessed using Spearman′s rank correlation. The area under the receiver operating characteristics curve was used to evaluate the accuracy of each parameter in predicting DMV, the critical value was determined, and the accuracy, sensitivity, specificity, positive and negative predictive values were calculated. Results:The modified Mallampati classification, rating of the upper lip bite test, ultrasonic tongue longitudinal cross-sectional area, transverse diameter of tongue and tongue volume were positively correlated with DMV, and thyromental distance and mandibular condylar motion were negatively correlated with DMV ( P<0.05). The area under the receiver operating characteristics curve of mandibular condylar motion and tongue volume in predicting DMV were 0.898 and 0.862, respectively, the cut-off values were 1.19 cm and 99.94 cm 3, respectively, and the sensitivity and specificity were all over 70% and 90%, respectively, the positive predictive values were 92.31% and 88.46%, respectively. Conclusions:Ultrasonic measurements of mandibular condylar motion and tongue volume can accurately predict DMV.

Objective:To investigate the correlation between gallbladder polyps and colon polyps of different locations.Methods:Healthy subjects who underwent colonoscopy in the Physical Examination Center of the Affiliated Hospital of Yangzhou University from January 2020 to October 2022 were included. They were divided into the proximal colon group and the distal colon group according to the location of colon polyps. Gallbladder polyps were compared with other known risk factors for colon cancer. Different parts and types of polyps were further explored.Results:A total of 2 811 patients had colon polyps, including 1 668 males and 1 143 females, with an average age of 47.3 years. One hundred and seventy-one (6.1%) had gallstones, and 459 (16.3%) had gallbladder polyps. The incidence of gallbladder polyps was higher in the proximal colon polyp group (21.7%, 93/429). Gallbladder polyps were independently associated with proximal colon polyps, including hyperplastic polyps ( OR=1.525, P=0.029) and adenomatous polyps ( OR=1.425, P=0.017). There was no significant correlation between gallbladder polyps and distal colon polyps. Conclusion:Gallbladder polyps are associated with proximal colon polyps, and colonoscopy screening is recommended for people with gallbladder polyps.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an extracorporeal life support strategy for the treatment of critically ill children with reversible heart and lung failure, increasingly being used in patients with low cardiac output after cardiac surgery. However, the mortality of patients is closely related to the complications of ECMO, especially bleeding, thrombosis, and infection, ECMO-related nosocomial infection has become a challenge to the success of ECMO. This study aims to analyze the incidence and risk factors for venoarterial-ECMO (VA-ECMO)-related nosocomial infections in children after cardiac surgery. METHODS: We retrospectively collected the data of patients who underwent VA-ECMO treatment after pediatric cardiac surgery in the Second Xiangya Hospital of Central South University from July 2015 to March 2021, and divided them into an infected group and a non-infected group. The clinical characteristics of the 2 groups of patients, VA-ECMO-related nosocomial infection factors, pathogenic microorganisms, and patient mortality were compared. Logistic regression was used to analyze the risk factors for nosocomial infection related to VA-ECMO after cardiac surgery. RESULTS: Of the 38 pediatric patients, 18 patients (47.37%) had VA-ECMO related nosocomial infection, served as the infected group, including 7 patients with blood infections and 11 respiratory tract infections. Gram-negative pathogens (16 strains, 88.9%) were the main bacteria, such as Acinetobacter baumannii (6 strains), Klebsiella pneumoniae (3 strains), and Stenotrophomonas maltophilia (3 strains). Compared with the non-infected group (n=20), the infection group had longer time of cardiopulmonary bypass, time of myocardial block, and time of VA-ECMO assistance (All P<0.05). Multivariate logistic regression analysis showed that time of cardiopulmonary bypass (OR=1.012, 95% CI 1.002 to 1.022; P=0.021) was an independent risk factor for ECMO-related nosocomial infection. The number of surviving discharges in the infected group was less than that in the non-infected group (1 vs 11, P<0.05). CONCLUSIONS Cardiopulmonary bypass time is an independent risk factor for VA-ECMO-related nosocomial infection in children after cardiac surgery. Shortening the duration of extracorporeal circulation may reduce the incidence of VA-EMCO-related nosocomial infections in children after cardic surgery. The occurrence of VA-ECMO-related nosocomial infections affects the number of patient's discharge alive.
Cardiac Surgical Procedures/adverse effects* ; Child ; Cross Infection/etiology* ; Extracorporeal Membrane Oxygenation/adverse effects* ; Humans ; Retrospective Studies ; Risk Factors

Background: The systemic immune inflammation index (SII) is a reproducible biomarker of inflammatory process. Aims: To explore the predictive value of SII for severe acute pancreatitis (SAP). Methods: A total of 406 patients with acute pancreatitis (AP) from Jan. 2013 to Dec. 2020 at Affiliated Hospital of Yangzhou University were collected, and were divided into SAP group and non SAP group. ROC curve was drawn to evaluate the value of SII, NLR, PLR, CAR for predicting SAP. Results: Compared with non‑SAP group, SII, NLR, PLR, CAR were significantly increased in SAP group (P<0.05). When the best cut‑off value was 1 705.83, AUC of SII for predicting SAP was 0.754, the sensitivity was 75.47%, and the specificity was 69.12%. AUC of SII for predicting SAP was higher than that of PLR, CAR (Z=2.647, P=0.007; Z= 2.616, P=0.008), while no significant difference was found between SII and NLR (P>0.05). And no significant difference in AUC was found between PLR and CAR (P>0.05). Conclusions: SII is a good new hematological index that can be used to predict the severity of AP, its predictive ability is similar to NLR, better than PLR and CAR.

Objective:To develop the Health Promotion Behavior Intention Questionnaire for enterostomy patients and test its reliability and validity.Method:Based on the theory of planned behavior, the first draft of the questionnaire was formed through literature review, group discussion, correspondence with Delphi experts and pre-test. The convenient sampling method was used to select 419 patients with enterostomy who visited Stoma Outpatient Department of the Affiliated Hospital of Qingdao University from December 2020 to June 2021 to conduct a questionnaire survey. Item analysis and reliability and validity tests were carried out on the questionnaires.Results:The Health Promotion Behavior Intention Questionnaire for enterostomy patients included 15 items. Exploratory factor analysis extracted four common factors, namely, attitude, subjective norm, perceived behavioral control and behavioral intention. The cumulative variance contribution rate was 83.166%. The content validity index of item level was 0.875-1.000 and the content validity index of questionnaire level was 0.983. The Cronbach's α coefficient of the total questionnaire was 0.921 and the retest reliability coefficient was 0.848.Conclusions:The Health Promotion Behavior Intention Questionnaire for enterostomy patients has good reliability and validity and it can be used as a tool to evaluate the health promotion behavior intention of patients with enterostomy.

The clinical application of triptolide (TPL) in tumor therapy has been greatly limited by its toxicity and inefficient delivery. Herein, a localized and sustained-release thermo-sensitive hydrogel was developed for the intra-tumor administration of TPL. Based on the amphiphilic structure of poly (

Objective The paper aims to analyze the effectiveness and problems of health personnel construction in China since 2012,provide reference for promoting the construction of health professionals.Methods Using national data from China health statistics yearbook,adopted the methods of descriptive statistics and literature research and so forth.Results The construction of health personnel has been continuously strengthened in China,the structure and distribution of health personnel have been further optimized,the medical service capabilities have been improved.However,there are still inappropriate or imbalanced situations.Conclusions The construction of key personnel such as primary health personnel and urgently needed personnel need to be further strengthened;promote the construction of health service personnel to meet new health needs;continue to improve the construction of high-level and management personnel to play a leading role.