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 status of disability acceptance in patients with permanent bladder fistula and analyze the influencing factors.Methods:Using the convenience sampling method, 218 patients who were hospitalized in urology from January 2018 to June 2019 were selected as the research subjects. A general data questionnaire, a disability acceptance scale (revised edition), a social impact scale, and a state self-esteem scale were used to investigate 218 patients with permanent cystostomy.Results:The score of disability acceptance in patients with permanent bladder fistula was (82.6±6.9) points, which was moderate, and 49.5% (108/218) of patients with moderate level of disability acceptance. Multiple linear regression analysis showed that the total score of social impact, total score of state self-esteem, age, average monthly household income, postoperative time of ostomy and disability acceptance were important factors ( t values were -8.726-5.786, P<0.05 or 0.01). Conclusion:The degree of disability acceptance in patients with permanent bladder fistula is at a moderate level. It is recommended that relevant nursing staff should encourage patients to receive the effects of ostomy on the body image, and provide support to patients and families to help patients cope with the social environment.

BACKGROUND: Studies have shown that chitosan can improve the proliferation and migration of fibroblasts, promote the synthesis of extracellular matrix, and create a favorable environment for defect healing.OBJECTIVE: To observe the effect of highly simulated chitosan scaffolds in repairing abdominal wall defects in rats.METHODS: Sixty adult Sprague-Dawley rats were used to make animal models of abdominal wall defects, and then model rats were randomly divided into two groups: experimental group and control group followed by implantation with the highly simulated chitosan scaffold and polypropylene mesh, respectively. At 2, 4 weeks after repair, gross, adhesion and histopathological observations of the repair part were performed.RESULTS AND CONCLUSION: Gross observation: in the control group, omental adhesion was found at 2 weeks after repair; and at 4 weeks after repair, the mesh was thickened and exhibited clear boundaries with the surrounding tissue, but common color and integration. In the experimental group, there was mild adhesion between the scaffold and the defect site at 2 weeks after repair, and the mesh was thickened, but the wound healed well with no prominence, swelling, and infection at 4 weeks after repair. Kadata adhesion score in the experimental group was lower than that the control group at 4 weeks after repair (P < 0.05). Pathological observation showed that at 4 weeks after repair, there were a large number of infiltrated inflammatory cells, capillary growth, and a large number of fibroblasts at the defect site in the control group; and meanwhile, a small amount of infiltrated inflammatory cell infiltration and a large number of collagen fibers and capillaries, with better granulation tissue maturity,were found in the experimental group. To conclude, the highly simulated chitosan scaffold can promote the repair of abdominal wall defects and reduce inflammatory reactions.

The HPLC fingerprint differences ofRadix Platycodonis from different origins were studied to provide references for their quality control and production. The total platycodins were purified by DB101 macroporous resin. HPLC-ELSD fingerprints of the total platycodins for 39 batches ofRadix Platycodonis samples from 9 provinces were performed on an Agilent HC-C8 column (4.6 mm x 250 mm, 5μm) with gradient elution. The mobile phase was acetonitrile-0.5% acetic acid. The injection volume was 6μL. The flow rate was 0.5 mL·min-1. The temperature of drift tube was set at 90℃. And the gas flow (N2) was set at 1.2 mL·min-1. The results showed that there were large differences in the quality ofRadix Platycodonis from different origins with the common fingerprints of 6 batches of samples fromChifeng in Inner Mongolia as references. The quality ofRadix Platycodonis was closely related to the seeds, the ecological environment, the way of drying and storing and so on. It was concluded that it was important to strengthen the provenance base construction, standardization of the seeds, reasonable formulation of the regionalization, and standardization of the production processing for the cultivation and production ofRadix Platycodonis.

This study was aimed to compare the expectorant and antitussive actions ofPlatycodon grandilforum from different production areas in order to provide references for its cultivation and production. The antitussive activities ofP. grandilforum water extract from different areas were investigated through testing the cough times induced by ammonium hydroxide in mice. And the expectorant activities were studied by testing the amount of tracheal phenolsulfonphthalein excretion in mice. The results showed that the minimum effective dose ofP. grandiflorum fromChifeng of Inner Mongolia was 0.2 g·kg-1. Under this dosage,P. grandiflorum fromChifeng of Inner Mongolia can significantly reduce the cough frequency in mice (P < 0.01), and significantly prolong the cough incubation period in mice (P < 0.01).P. grandiflorum fromSichuan province,Shangzhou ofShaanxi province andChongqing can significantly decrease the cough frequency in mice (P < 0.05). P. grandiflorum from Sichuan province,Shangzhou ofShaanxi province andChifeng of Inner Mongolia can significantly increase the phenolsulfonphthalein excretion quantity in mice (P < 0.05). It was concluded thatP. grandilforum was effective for relieving cough and removing sputum. The effect ofP. grandilforum fromChifeng of Inner Mongolia was obviously stronger than that from other areas.

OBJECTIVETo evaluate the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in children with pancreaticobiliary diseases and the characteristics of pancreaticobiliary disorders in children.

METHODRetrospective review was conducted on the data of patients younger than 18 years who underwent ERCP between 2005 and 2012 at West China Hospital. The indications,ERCP findings, ERCP procedures, complications, and clinical outcomes were evaluated.ERCP procedures were performed using standard duodenoscopes under general anaesthesia or sedation, which included all endoscopic treatments, such as endoscopic sphincteropapillotomy, stone extraction, stent treatment and so on.

RESULTOne hundred and two ERCPs were performed on 68 patients, and all the procedures were successfully completed in 100% cases. There were 39 girls (57%), and median age at time of procedure was 14.6 years (range, 5-17 years).General anesthesia and sedation were performed in 81% and 19% of procedures, respectively. The ERCP findings were classified as follows:bile duct stone(s) (n = 37, 54%), pancreatic duct stone(s) (n = 8, 12%), bile duct benign stricture (n = 7, 10%) and other nonmalignant pancreaticobiliary diseases (n = 16, 24%).Four cases (4/102, prevalence 4%) were complicated with post-ERCP pancreatitis.Symptoms such as abdominal pain and jaundice were cured obviously after the procedures of ERCP were performed.

CONCLUSIONThe main characteristics of pancreaticobiliary disorders in children were nonmalignant pancreaticobiliary diseases, such as bile duct stone, pancreatic duct stone, and bile/pancreatic duct benign stricture.When performed by well-trained endoscopists, ERCP is safe and effective in children.

Adolescent ; Biliary Tract Diseases ; diagnostic imaging ; surgery ; Calculi ; diagnosis ; pathology ; surgery ; Child ; Child, Preschool ; Cholangiopancreatography, Endoscopic Retrograde ; Choledocholithiasis ; diagnosis ; pathology ; surgery ; Female ; Humans ; Male ; Pancreatic Diseases ; diagnosis ; pathology ; surgery ; Pancreatic Ducts ; diagnostic imaging ; surgery ; Retrospective Studies ; Treatment Outcome

Objective To investigate the role of tumor necrosis factor-α (TNF-α) on eryptosis.Methods Erythrocytes isolated from mice were put under the treatment of TNF-α at the dose of 1ng/ml for 6,12,24,48 and 72 h,or at different concentrations of 0.1,1 and 10 ng/ml for 24 h.The forward scatter (FSC),phosphatidylserine (PS)exposure and ceramide formation were determined by flow cytometry.Results Compared to control group,the decrease of FSC ((81.5 ± 1.02)％ vs (87.6 ± 0.55)％,P＜0.05),the increasment of membrane PS exposure level and ceramide content ((5.5±1.07)％ vs (2.7±0.17)％,(2.1±0.23)％ vs (0.7±0.26)％,P＜0.01) were observed in erythrocyte under the treatment of TNF-α for 24 h with more obvious tendency over time.Conclusions TNF-α can trigger cell shrinkage,and promote PS exposure and ceramide formation on the membrane of erythrocyte.

Objective To investigate the morphologic change and phosphatidylserine (PS) exposure of erythrocytes in sepsis patients.Methods 30 healthy volunteers (control group)and 30 sepsis patients were enrolled in this study and were collected venous sampling.Monitoring included Wright's staining blood smear test,erythrocyte aggregation index and the ratio of PS exposure of erythrocytes.A flow-cytometric assay based on FITC-Annexin V was used to measure the PS exposure of erythrocytes.Results The morphological changes of red blood cells included acanthocyte,lachrymiform,rouleaux,spherocyte in sepsis patients,and the peripheral blood erythrocyte aggregation and aggregation index were significantly higher than that of the healthy control group (P＜0.05).The percentage of PS exposure of erythrocytes in sepsis patients were significantly higher than that of healthy volunteers (P＜0.001).Conclusion The PS exposure of erythrocytes were significantly higher in sepsis patients,and the morphology of red blood cells is obvious abnormal.

Objective This study is to discuss the effects of cognitive therapy on life quality of rural breast cancer patients during chemotherapy in order to offer evidence for choosing the appropriate therapeutic measures.Methods 120 rural breast cancer patients were equally divided into the intervention group and the control group at random.The usual care plus cognitive treatment was given to the patients in the intervention group for 6 months,while only the usual care after chemotherapy was given to the control group.The quality of life assessments were carried out to both groups on the 5th day during hospitalization,and the first,third and 6th month during recheck period of time,respectively.The treatment effect was observed.Results There were statistical significant difference of the total scire of life quality assessment on the 5th day,the first,third and 6th month,respectively,between the intervention group and the control one after cognitive intervention.The downtrend of total score of quality of life in the intervention group after cognitive intervention was more significant than the control group,which indicated the quality of life of the intervention group was better than the control group. Conclusions Cognitive therapy is an efficient method to enhance the quality of life of rural breast cancer patients during chemotherapy.

Bulk erosion type biodegradable materials play an important role in pharmaceutics.However,the instability of carriers affects drug delivery systems critically,and complicates their drug release kinetics.Among these problems,how degradation and erosion affect drug release patterns becomes a focus.Mathematical models facilitate to understand complex pharmaceutical drug release patterns,and are easily applied in structure design of drug delivery systems and to predict their drug release kinetics.This paper reviews the degradation and erosion patterns,drug release mechanisms,and the recent research of mathematical models.