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 impact of the three-level assistance model based on the narrative nursing theory on the mental health status of medical staff.Methods 140 medical staff working in a third class hospital in Xiangyang City were selected as the research object.The three-level assistance model based on narrative nursing theory was used to intervene them from September 2021 to July 2022.The symptom self-assessment scales before and after the intervention were compared.Results Before the intervention,the total score of SCL-90(156.37±32.56)points and the scores of various symptom factors of medical staff were higher;After the intervention,the total score of SCL-90(133.35±43.48)points and the scores of various symptom factors were lower than those before the intervention and the difference was statistically significant(P<0.05).Conclusion The three-level assistance model based on narrative nursing theory can reduce the total score of SCL-90 and the scores of various symptom factors,improve the mental health status and mental health level.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

BACKGROUND/OBJECTIVES: To identify modifiable risk factors for type 2 diabetes mellitus and explore the relationship between diet sodium intake and blood glucose levels.MATERIALS/METHODS: Based on inclusion and exclusion criteria, we extracted, analyzed, and assessed the available crossover studies of dietary salt intake restriction and insulin resistance in PubMed, Web of Science, MEDLINE, Embase, Wanfang, and CNKI databases. RESULTS: We included 6 studies with 8 sets of data, covering 485 subjects. I2 statistics results showed insignificant heterogeneity among all data (I 2 = 39.2% < 50%). Thus, a fixed-effect model was adopted for the final pooled effect size. Weighted mean difference and its 95% confidence interval (CI) value was 0.193 (95% CI, 0.129–0.257), and the test of the overall effect showed P < 0.001. The results revealed that the blood glucose levels in the subjects in the low-salt intake group were significantly higher than those in the normal or high-salt intake groups. We also found no significant change occurred after the removal of any study through sensitivity analysis, which confirmed that the outcome we calculated was prudent and credible. The quantitative Egger’s test (P = 0.109 > 0.05) indicated that insignificant publication bias existed. CONCLUSION This meta-analysis highlights the relationship between dietary sodium intake and blood glucose levels. Our findings show that higher blood glucose levels might be expected in hypertensive or normal people with low-salt consumption compared to those with normal or high-salt consumption, although these differences were not clinically significant.Trial Registration: PROSPERO Identifier: CRD42021256998

Objective:Improve the quality of clinical research at different stages for better protection of human subject.Methods:Introduce the operational and the administrative experiences of establishing the human research protection program in our hospital.Results:Establish human research protection program can promote the direct communication and cooperation among relevant departments of clinical research, strengthen the whole process management of clinical research.Conclusions:Developing comprehensive human research protection program and related policies play a positive role in promoting the high-quality development of clinical research in hospitals.

Objective:To evaluate the middle cerebral artery blood flow velocity in children with electrical status epileptic during sleep (ESES) by transcranial Doppler (TCD)-video electroencephalography (VEEG), and analyze its clinical significance.Methods:The clinical data of 40 children with ESES (ESES group) in Zhangjiakou First Hospital of Hebei Province from January 2019 to January 2021 were retrospectively analyzed. The mean flow velocity of middle cerebral artery (MCA mean) and middle cerebral artery (MCA) flow fluctuation value during deep sleep were measured by TCD-VEEG, and the results were compared with 40 healthy children (healthy control group) during the same period. The relationship between MCA mean, MCA flow fluctuation value during deep sleep and clinical characteristics was analyzed by multivariate stepwise regression. Results:The MCA mean and MCA flow fluctuation value during deep sleep in ESES group were significantly higher than those in healthy control group: (17.87 ± 7.38)% vs. (2.07 ± 1.11)% and (92.92 ± 21.64) cm/s vs. (58.11 ± 8.04) cm/s, and there were statistical differences ( t = 13.389 and 9.536, P<0.01). There was no statistical difference in MCA mean and MCA flow fluctuation value during deep sleep in children with benign epilepsy with central temporal spinous wave (16 cases), benign epilepsy variant with central temporal spinous wave (13 cases) and acquired epileptic aphasia (11 cases) ( P>0.05). There was no statistical difference in MCA mean and MCA flow fluctuation value during deep sleep in children with multifocal epileptic foci (16 cases), bilateral asymmetric epileptic foci (16 cases) and bilateral synchronous symmetric epileptic foci (8 cases)( P>0.05). The MCA flow fluctuation value during deep sleep in children with absolute synchronization and fully generalized ESES (16 cases) was significantly higher than that in children with asymmetric ESES (24 cases): (22.37 ± 2.37)% vs. (15.37 ± 5.37)%, and there was statistical difference ( t = 4.890, P<0.01); there was no statistical difference in MCA mean during deep sleep between 2 types of children ( P>0.05). The MCA flow fluctuation value during deep sleep in children with non obvious cognitive impairment (14 cases), mild cognitive impairment (13 cases) and severe cognitive impairment (13 cases) was (14.21 ± 5.20)%, (17.97 ± 7.45)% and (22.10 ± 7.94)%, and there was statistical difference ( F = 4.376, P<0.05); there was no statistical difference in MCA mean during deep sleep in 3 types of children ( P>0.05). Multivariate stepwise regression analysis result showed that the MCA flow fluctuation value during deep sleep had positive correlation with the degree of cognitive impairment in children with ESES ( r = 0.391, P<0.05). Conclusions:The fluctuation value of MCA during deep sleep by TCD-VEEG examination is positively correlated with the degree of cognitive impairment in children with ESES, which may be a reliable way for clinical evaluation of the degree of cognitive impairment in children with ESES.

Objective:To explore the application effect of narrative nursing in long-term primary family caregivers of maintenance hemodialysis patients.Methods:Using the convenient sampling method, a total of 120 main family caregivers of maintenance hemodialysis patients who received hemodialysis treatment in Hemodialysis Room of a tertiary general hospital were selected as the research objects from May to August 2020. The patients were randomly divided into the observation group ( n=60) and the control group ( n=60) by random number table method. The observation group was given narrative nursing intervention, while the control group was given routine psychological nursing. Zarit Caregiver Burden Interview (ZBI) , Self-rating Anxiety Scale (SAS) and Beck Depression Scale (BDI-Ⅱ) were used to investigate the situation of caregivers in the two groups. Results:Before the intervention, there was no statistically significant difference in the total scores of ZBI, SAS and BDI-Ⅱ between the two groups ( P>0.05) . After the intervention, the total scores of ZBI, SAS and BDI-Ⅱ in the observation group were respectively 23.50 (15.00, 33.00) , 33.00 (27.00, 41.00) and 11.00 (8.00, 14.75) , which were lower than the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Narrative nursing can effectively reduce the long-term care burden of the main family caregivers of maintenance hemodialysis patients and reduce levels of anxiety and depression, which is worthy of clinical application.

OBJECTIVE: To explore the genetic basis for a patient with Leydig cell hypoplasia. METHODS: Whole exome sequencing was used to detect genetic variants in the patient. Suspect variants were verified by PCR and Sanger sequencing of the family members. RESULTS: The patient was found to carry two novel variants, namely c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala), of the luteinizing hormone receptor gene (LHCGR), where were respectively inherited from her father and mother. Upon prenatal diagnosis, the fetus was found to be a heterozygous carrier of the c.265A>T (p.Ile189Leu) variant. CONCLUSION The compound heterozygous variants of c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala) of the LHCGR gene probably underlie the Leydig cell hypoplasia in the patient.

In recent years, public emergencies, especially public health emergencies, have occurred frequently. In the process of emergency rescue, there is often a shortage of emergency medical supplies. Public donation is one of the effective ways to alleviate the shortage of emergency medical supplies. In this paper, the authors analyzed the problems of public hospitals accepting social donations in public health emergencies, discussed the legal risks, and put forward countermeasures and suggestions for relevant departments.

Objective: To establish an intensity-classified Chinese facial emotion image database and provide materials for emotional researches in China. Methods: Firstly, under the guidance of professional director, 22 professional dramatic actors put up seven kinds of emotion, including anger, disgust, fear, sadness, surprise, happy and calm. The process of facial emotional performance of actors were filmed by a high-speed camera. Then we made screen captures according to the intensity of emotion performed by the actors. A total of 814 black-and-white photographs with same size and gray level were made after we removed the irrelevant parts to the facial features. Each kind of emotion contains six levels of intensity scoring from 1 to 6. Totally, 112 healthy volunteers were recruited to evaluate the emotional intensity, pleasure and arousal of all images via a visual scale ranged from 0 to 100. Results: A Chinese face emotional intensity hierarchical picture library was set up, which contained 2 sublibraries. The first library was consisted of 436 images with hierarchical emotional intensity images collected from different performers. The second one was built with 640 images, in which the hierarchical emotional intensity image was collected from same actor/actress. Both image libraries had corresponding scores for intensity, pleasure, and arousal. Furthermore, both exhibited a high degree of internal consistency in reliability analysis (with a Cronbach' s alpha value larger than 0. 9). Conclusion: The present study has established an intensity-classified Chinese facial emotion image database with good recognition degree and psychological measurement attribution, which could provide materials for emotional researches in China.