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 construct an evaluation indicator system for the efficiency of nursing human resources in integrated medical and elderly care institutions using Data Envelopment Analysis (DEA) and subsequently evaluate its effectiveness.Methods:This cross-sectional survey utilized literature review and investigative methods to initially establish a library of evaluation indicators for nursing human resource efficiency. The Delphi method was employed in two rounds of consultations with 17 experts from various fields, including nursing management, elderly care institution management, integrated medical and elderly care institution management, health economics management, and public health. The reliability of the indicator system was assessed based on factors such as expert enthusiasm, authority, concentration of opinions, and coordination. Adjustments, modifications, and improvements were made to the indicators based on expert opinions to establish the final indicator system. From August to December 2022, the DEA model was applied to evaluate the efficiency of 12 integrated medical and elderly care institutions in Haikou city based on this indicator system.Results:The constructed evaluation indicator system comprised 68 items divided into three levels: 9 primary indicators, 19 secondary indicators, and 40 tertiary indicators. The positive coefficients of the two rounds of expert consultations were 100% and 94.1%, with authority coefficients of 0.88 and 0.92, Kendall harmony coefficients of 0.471 and 0.348, and mean coefficients of variation of 0.16 and 0.12 ( P<0.001). DEA evaluation results for the 12 integrated medical and elderly care institutions showed that 5 were DEA effective institutions with comprehensive efficiency (OE), technical efficiency (TE), and scale efficiency (SE) values all equal to 1.000, while 7 were non-DEA effective institutions, including 4 with SE <1.000 but TE=1.000 and 3 with both SE and TE<1.000. Conclusions:The constructed evaluation indicator system demonstrates high enthusiasm, authority coefficients, and coordination in expert consultations, indicating high acceptability and comprehensive content with distinct levels and strong specialty characteristics. The DEA model′s evaluation results objectively and effectively reflect the efficiency of nursing human resources in integrated medical and elderly care institutions, demonstrating practical utility.

BACKGROUND/OBJECTIVES: Soy isoflavone (SIF) and soy lecithin (SL) have beneficial effects on many chronic diseases, including neurodegenerative diseases. Regretfully, there is little evidence to show the combined effects of these soy extractives on the impairment of cognition and abnormal cerebral blood flow (CBF). This study examined the optimal combination dose of SIF + SL to provide evidence for improving CBF and protecting cerebrovascular endothelial cells.MATERIALS/METHODS: In vivo study, SIF50 + SL40, SIF50 + SL80 and SIF50 + SL160 groups were obtained. Morris water maze, laser speckle contrast imaging (LSCI), and hematoxylineosin staining were used to detect learning and memory impairment, CBF, and damage to the cerebrovascular tissue in rat. The 8-hydroxy-2′-deoxyguanosine (8-OHdG) and the oxidized glutathione (GSSG) were detected. The anti-oxidative damage index of superoxide dismutase (SOD) and glutathione (GSH) in the serum of an animal model was also tested. In vitro study, an immortalized mouse brain endothelial cell line (bEND.3 cells) was used to confirm the cerebrovascular endothelial cell protection of SIF + SL. In this study, 50 μM of Gen were used, while the 25, 50, or 100 μM of SL for different incubation times were selected first. The intracellular levels of 8-OHdG, SOD, GSH, and GSSG were also detected in the cells. RESULTS: In vivo study, SIF + SL could increase the target crossing times significantly and shorten the total swimming distance of rats. The CBF in the rats of the SIF50 + SL40 group and SIF50 + SL160 group was enhanced. Pathological changes, such as attenuation of the endothelium in cerebral vessels were much less in the SIF50 + SL40 group and SIF50 + SL160 group. The 8-OHdG was reduced in the SIF50 + SL40 group. The GSSG showed a significant decrease in all SIF + SL pretreatment groups, but the GSH showed an opposite result. SOD was upregulated by SIF + SL pretreatment. Different combinations of Genistein (Gen)+SL, the secondary proof of health benefits found in vivo study, showed they have effective antioxidation and less side reaction on protecting cerebrovascular endothelial cell. SIF50 + SL40 in rats experiment and Gen50 + SL25 in cell test were the optimum joint doses on alleviating cognitive impairment and regulating CBF through protecting cerebrovascular tissue by its antioxidant activity. CONCLUSIONS SIF+SL could significantly prevent cognitive defect induced by β-Amyloid through regulating CBF. This kind of effect might be attributed to its antioxidant activity on protecting cerebral vessels.

Loofah seeds ribosome inactivating protein luffin-α was fused with a tumor-targeting peptide NGR to create a recombinant protein, and its inhibitory activity on tumor cells and angiogenesis were assessed. luffin-α-NGR fusion gene was obtained by PCR amplification. The fusion gene was ligated with pGEX-6p-1 vector to create a recombinant plasmid pGEX-6p-1/luffin-α-NGR. The plasmid was transformed into E. coli BL21, and the target protein was isolated and purified by GST affinity chromatography. The luffin-α-NGR fusion gene with a full length of 849 bp was successfully obtained, and the optimal soluble expression of the target protein was achieved under the conditions of 16 ℃, 0.5 mmol/L IPTG after 16 h induction. SDS-PAGE and Western blotting confirmed the recombinant protein has an expected molecular weight of 56.6 kDa. Subsequently, the recombinant protein was de-tagged by precision protease digestion. The inhibitory effects of the recombinant protein on liver tumor cells HepG2 and breast cancer cells MDA-MB-231 were significantly stronger than that of luffin-α. The Transwell and CAM experiment proved that the recombinant protein luffin-α-NGR also had a significant inhibitory effect on tumor cells migration and neovascularization. The inhibitory activity on tumor cells and angiogenesis of the recombinant luffin-α-NGR protein lays a foundation for the development of subsequent recombinant tumor-targeting drugs.
Electrophoresis, Polyacrylamide Gel ; Escherichia coli/metabolism* ; Plasmids ; Recombinant Proteins/pharmacology* ; Saporins/metabolism*

Objective:To construct the scheme of palliative care for nursing undergraduates based on competency outcomes and performance assessment (COPA) model, and to provide reference for palliative care course.Methods:The research period is from March to December in 2020. Based on Lenburg's COPA model, the first draft of the curriculum scheme was constructed through literature research and focus group interview, and 23 experts were invited to modify the content to determine the final versions of curriculum scheme.Results:The response rate of the two rounds of questionnaires were 100.0% and 91.3% respectively, and the expert authority coefficient were 0.80 and 0.82 respectively. After two rounds of Delphi procedure, the opinion of the experts was nearly consistent. The curriculum scheme contains 49 curriculum objectives, 70 theoretical contents, 5 practical contents and 9 teaching methods.Conclusions:The curriculum scheme of palliative care for nursing undergraduates based on COPA model is scientific and practical, which can provide guidance for undergraduate nursing.

Objective:To explore the effects of bridge in, objective, pre-assessment, participatory learning, post-assessment and summary (BOPPPS) on internal nursing teaching.Methods:Totally 220 nursing students enrolled into Zhengzhou University in 2017 were selected by convenient sampling and divided into the observation group and the control group according to the teaching mode, with 110 nursing students in each group. Nursing students in the control group receiving traditional teaching, while nursing students in the control group receiving BOPPPS teaching. The effect of the two teaching modes was compared.Results:The satisfaction rate of the observation group (98.2%) was higher than that of the control group (90.0%) , and the difference was statistically significant ( P<0.05) . The assessment results of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.01) . The total score of self-evaluation of learning effect and the score of each dimension in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The BOPPPS model shows satisfying effects in internal nursing teaching, which can increase the satisfaction of students with the teaching mode, and enhance their interest in learning, academic performance, and learning evaluation.

Objective: To evaluate the short-term efficacy of branched TEVAR in the treatment of complex aortic arch lesions. Methods: The clinical data of 18 patients with aortic lesions requiring reconstruction of the left subclavian artery who were treated with branch TEVAR technology in Tianjin Medical University General Hospital from Apr 2016 to Dec 2018 were analyzed retrospectively. Results: There were 16 cases using Castor external branch stent implantation and 2 cases of self-made internal branch stent. The success rate of device release was 100%, the success rate of operation was 100%, and there were no intraoperative deaths. Postoperative complications occurred in 2 cases: one proximal stent tear dissection required open surgery, one died of massive myocardial infarction.Seventeen patients were followed up for 1-8 months. CTA examination in 16 patients 30 days after surgery, found 1 patient with type Ⅲ endoleak. CTA examination done in 8 patients 6 months after surgery found distal occlusion of left subclavian artery stent in 1 patient necess itating distal stent implantation. Conclusion The branch TEVAR technique is effective method to reconstruct the arch branched artery.

Objective:To explore the utilization of and satisfaction at community health service between migrant and non-migrant workers in Shenzhen city. Methods: Random sampling was used and 8000 community residents in Shenzhen city were investigated, and the data was analyzed with SPSS 18. 0. Results:There was statistically signifi-cant difference on the times of seeking community health services last year between migrant workers and non-migrant workers ( P<0. 0001 ) , and the proportion of more than three times service utilization of migrant workers were greater than that of non-migrant workers. The top three elements inpluencing satisfaction at community health service between migrant and non-migrant workers were service attitude ( 73. 29% vs. 73. 46%) , technical level ( 65. 29% vs. 67. 50%), and its convenience of seeking a doctor (63. 16% vs. 64. 98%). 73. 47% of users (migrant workers:74. 16%, non-migrant workers:69. 71%) were willing to accept the system of first contact in community health in-stitutions. Conclusions:The utilization of community health service has increased since implementing the system of first contact in community health institutions. Both migrant workers and non-migrant workers were very satisfied with the community health services, and the differences on satisfaction between the two groups were not significant. It is feasible to gradually promote the system of first contact in community health institutions over China.

[ABSTRACT]OBJECTIVETo compare the differences of aerodynamic characteristics of pharyngeal cavity between normal subjects and OSAHS patients, and to study the nasal obstruction in the pathogenesis of the OSAHS.METHODSA total of 60 normal subjects and 60 OSAHS patients were enrolled in this study. Numerical simulation was performed to calculate the airflow dynamic indexes of three sections of pharyngeal cavity. Correlation analysis of the nasal resistance and negative pressure were studied.RESULTSThe average pharyngeal negative pressure and airflow velocity in OSAHS patients were significantly increased than that in normal subjects. The total nasal airway resistance significantly correlated with the average negative pressure of pharyngeal cavity. CONCLUSIONAirflow dynamic indexes of OSAHS patients had significant different pharyngeal aerodynamic characteristics from normal subjects. The increased average negative pressure in pharynx might contribute to the severity of pharyngeal collapse for OSAHS patients. Higher total nasal resistance might play a role in the pathophysiological mechanisms of OSAHS.

[ABSTRACT]OBJECTIVETo compare the aerodynamic differences before and after nasal cavity ventilation expansion techniques in patients with OSAHS. METHODSA total of 30 adult patients with OSAHS were included in this study. Pre-operative upper airway CT of each subject was acquired. Each subject underwent surgery. Postoperative upper airway CT was obtained at least 3 months later. By means of CFD simulation method, numerical simulation was performed to calculate the airflow dynamic indexes of the upper airway. The pre-and post-operative aerodynamic characteristics were compared. RESULTSAfter operation, post-operative negative pressure nephogram of the nasal cavity indicated more smooth variation of pressure gradient, post-operative velocity nephogram of nasal cavity indicated slower airflow velocity. Proper values of flow field indicated the volume of nasal cavity increased significantly (t=4.025,P<0.01), the total nasal airway resistance decreased significantly (t=-2.065,P<0.01). The total negative pressure of the upper airway decreased significantly (t=-2.659,P<0.01) after operation. However, the proper values of flow field increased in 5 patients. CONCLUSIONNasal cavity ventilation expansion effectively increase the volumes of nasal cavity, improve the nasal ventilation, and reduce the air flow velocity of both nasal cavity and pharynx in OSAHS patients, those reduce the pharyngeal negative pressure and the pharyngeal collapse. However, for patients with its narrowest segment at the velopharyngeal level, operation cannot do anything or even aggravate the pharyngeal collapse. Operation should be performed individually.