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 investigate the effect of individual exercise training on the rehabilitation of patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods A total of 81 patients between January 2021 and December 2023 were randomly allocated into an observation group(n=41)and a control group(n=40)using a simple random number Tab.method.The control group received routine post-operative rehabilitation intervention,while the observation group received individualized exercise training as the core component of cardiac rehabilitation intervention.The study compared the effects of rehabilitation,cardiac function parameters[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD)],exercise endurance measures[6-minute walking distance(6MWD)],and quality of life assessed by Seattle Angina Pecina Scale(SAQ)scores between the two groups before and after a three-month intervention period.Results The total recovery response rate in the observation group was higher than that in the control group(P＜0.05).LVEF,LVEDD,6 MWD,maximum exercise load and SAQ scales(P＞0.05),LVEF were higher than before intervention(t=3.345,2.480,3.165,5.016,2.059,4.582,4.443,3.353,P＜0.05),and LVEDD was lower than before intervention(t=3.335,P＜0.05).Conclusion The individualized exercise training-based cardiac rehabili-tation program demonstrates potential for enhancing cardiac function and exercise endurance in patients with CHD following PCI,thereby improving their overall quality of life.This finding holds significant clinical implications.

Objective To investigate current situations of emotional labour,career success and psychological resilience among the nurses and to explore the mediating role of psychological resilience between emotional labour and career success,hence to provide a reference in improvement of the sense of career success among the nurses.Methods Convenience sampling was used to select 922 clinical nurses from 15 Gade ⅡA hospitals in Hubei Province between June and July 2021.A general information questionnaire,the emotional labour scale,career success scale,and psychological resilience scale were used in the investigation.Pearson correlation was employed to analyse the correlations between emotional labour,career success and psychological resilience scores.Amos software was used to construct structural equation model to analyse the mediating effect.Results A total of 842 clinical nurses completed the survey.The total scores of career success and mental resilience of clinical nurses were(73.56±15.55)scores and(62.50±17.12)scores,respectively.In emotional labor,the surface acting dimension score was(20.46±5.92)scores.The score of deep acting dimension was(11.05±2.62),and the score of true emotion expression dimension was(11.95±3.48).Perceived career success was positively correlated with psychological resilience(r=0.593,P<0.001)Career success was negatively correlated with surface acting(r=-0.507,P<0.001).Career success was positively correlated with true emotional expression(r=0.481,P<0.001),and was positively correlated with deep acting(r=0.462,P<0.001).Psychological resilience was negatively correlated with surface acting(r=-0.452,P<0.001),positively correlated with true emotion expression(r=0.402,P<0.001),and positively correlated with deep acting(r=0.392,P<0.001).Psychological resilience plays a partial mediating role between the dimensions of emotional labor(surface acting,true emotional expression,deep acting)and career success,and the mediating effect is-0.146,0.108 and 0.112,accounting for 38.02%,32.05%and 37.21%of the total effect,respectively.Conclusion The three mensions of the emotional labor are at middle level and career success of clinical nurses is above the average level,but the psychological resilience is at a low level.In emotional labor,surface acting can directly negatively affect the ca reer success of clinical nurses,real emotion expression and deep acting can directly positively affect the career success of clinical nurses,and indirectly affect the career success of clinical nurses through the mediating effect of psychological resilience.Nursing managers should pay attention to the management of nurses'emotional labor,improve the level of psychological resilience,and then increase their sense of career success.

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.

Objective:To investigate the risk factors of initial non-invasive ventilation(NIV) failure and its association with adverse outcomes in very low birth weight infants (VLBWI).Methods:A retrospective cohort study was conducted, collecting clinical data of 2 102 VLBWI who received NIV within 30 minutes after birth, admitted to 18 NICU of Suxinyun Neonatal Perinatal Collaboration Network (SNPN) from January 1 st, 2019 to December 31 st, 2022. According to the outcome of NIV within the first 72 hours, the study cohort was divided into success group and failure group. Univariate analysis and multivariate Logistic regression analysis were performed to identify risk factors for NIV failure and its association with adverse outcome. Results:A total of 2 102 VLBWI were included, consisting of 1 078 males (51.3%). The gestational age was 29 (28, 31) weeks, and the birth weight was 1 250 (1 090, 1 380) g. The initial NIV failure rate was 15.3%(321/2 102). Multivariate Logistic regression analysis showed that smaller gestational age ( OR=0.67, 95% CI 0.61-0.74, P<0.001), maternal hypertensive disorders during pregnancy ( OR=10.31, 95% CI 7.48-14.21, P<0.001), Apgar score at the first minute ≤7 ( OR=1.40, 95% CI 1.01-1.93, P=0.042), grade 3-4 respiratory distress syndrome (RDS)( OR=2.85, 95% CI 1.69-4.81, P<0.001), ≥2 times pulmonary surfactant (PS) treatment ( OR=3.78, 95% CI 2.09-6.83, P<0.001), fraction of inspired oxygen (FiO 2)>0.30 ( OR=2.21, 95% CI 1.64-2.98, P<0.001) were all independent risk factors for initial NIV failure. The failure group had higher risks of mortality ( OR=10.19, 95% CI 6.50-15.97, P<0.001), pneumothorax ( OR=4.33, 95% CI 1.59-11.79, P=0.004), neonatal pulmonary hemorrhage ( OR=8.48, 95% CI 4.08-17.64, P<0.001), moderate to severe bronchopulmonary dysplasia (BPD)( OR=1.75, 95% CI 1.19-2.56, P=0.004), and intraventricular hemorrhage (IVH) ≥grade Ⅲ ( OR=2.18, 95% CI 1.27-3.73, P=0.004) compared to the success group. Conclusions:Small gestational age, maternal hyertensive disorders during pregnancy, Apgar score at the first minute ≤7, grade 3-4 RDS, PS treatment ≥2 times and FiO 2 >0.30 are risk factors for initial NIV failure in VLBWI. Initial NIV failure is associated with increased risk of mortality, pneumothorax, pulmonary hemorrhage, moderate to severe BPD, and IVH ≥grade Ⅲ.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Objective:To explore the methods of improving the clinical thinking ability of clinical medical interns in neurology department.Methods:Clinical medical interns from 2017 to 2018 were selected as the research subjects. The clinical medical interns in 2018 and in 2017 were set as the experimental group (98 people) and the control group (95 people). In the clinical practice of the neurology department, the experimental group was trained in clinical thinking ability, and the control group was trained by the traditional methods. Before the end of the internship, the self-made Clinical Medical Interns Clinical Thinking Ability Questionnaire was used to evaluate the teaching effect. SPSS 14.0 was used for t-test and Chi-square test. Results:The experimental group and the control group had the problems of one-sidedness, appearance, fixedness, passivity, laziness, simplification, confusion of clinical thinking. The clinical thinking problems in the experimental group were significantly improved than those in the control group ( P<0.001). There were significant differences in clinical thinking between the experimental group and the control group in terms of one-sidedness, appearance, fixedness, passivity and laziness ( P<0.05). In addition to language communication and expression ability, the self-assessment score of clinical thinking ability in the experimental group was statistically different from that in the control group ( P<0.05). Compared with the control group, there were also significant differences in the examination results of the experimental group ( P< 0.05). Conclusion:The implementation of clinical thinking training in neurology practice is conducive to cultivating students' clinical thinking ability and improving the quality of personnel training.

Major depressive disorder (MDD) is characterized by emotion dysregulation. Whether implicit emotion regulation can compensate for this deficit remains unknown. In this study, we recruited 159 subjects who were healthy controls, had subclinical depression, or had MDD, and examined them under baseline, implicit, and explicit reappraisal conditions. Explicit reappraisal led to the most negative feelings and the largest parietal late positive potential (parietal LPP, an index of emotion intensity) in the MDD group compared to the other two groups; the group difference was absent under the other two conditions. MDD patients showed larger regulatory effects in the LPP during implicit than explicit reappraisal, whereas healthy controls showed a reversed pattern. Furthermore, the frontal P3, an index of voluntary cognitive control, showed larger amplitudes in explicit reappraisal compared to baseline in the healthy and subclinical groups, but not in the MDD group, while implicit reappraisal did not increase P3 across groups. These findings suggest that implicit reappraisal is beneficial for clinical depression.
Humans ; Depressive Disorder, Major/psychology* ; Emotional Regulation ; Depression ; Emotions/physiology* ; Cognition/physiology*

【Objective:】 To construct a palliative care training course for medical student volunteers, so as to provide reference for palliative care institutions to carry out palliative care training for medical student volunteers. 【Methods:】 Based on literature review, semi-structured interviews and the expert group meeting method, the first draft of the palliative care training course for medical student volunteers was drawn up. Then two rounds of expert consultation with 16 experts in relevant fields by Delphi method was conducted. 【Results:】 The positive coefficients of the two rounds of expert consultation were 89% and 100%, respectively. The expert authority coefficients of the two rounds were both 0.89. The Kendall coefficient of the second round was 0.196 to 0.328 (P<0.05). The final form of palliative care training course for medical student volunteers was consisted of 5 primary indicators (training objective, training content, training hour, training method, and assessment method), 23 secondary indicators, and 41 tertiary indicators. 【Conclusion:】 The palliative care training course for medical student volunteers is comprehensive and practical in content, scientific and reliable in construction, which can be used for hospice care institutions to provide palliative care volunteer service training for medical student volunteers, in order to improve the quality of volunteer service.