Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective:To investigate the ethics and existing problems of experimental animals in medical experiments and experimental teaching, and to formulate countermeasures so that animal ethics and animal welfare can be truly reflected in medical experiments.Methods:In this study, a "Basic Function Experiment Center Animal Experiment Questionnaire" with 25 questions was formulated from three aspects: the ethical cognition of experimental animals, whether animal experiments are ethical or not, how to view the problems of animal ethics and experimental teaching and the cognition of virtual simulation experiment teaching. Questionnaire was sent to Hubei University of Medicine to investigate the international students of Batch 2017 (5-year program), undergraduates of Batch 2017 (5-year program) and nursing students of Batch 2018 (4-year program) as well as teachers, researchers and employees of laboratory animal center (all with bachelor degree or above). The survey results were expressed as percentage.Results:The recovery rate of the questionnaire in this study was 98.04%(2 451/2 500), among which the practitioners, teachers and researchers in the laboratory animal center clearly understood the ethics of experimental animals, but there was a widespread phenomenon of lagging ethics among the students. For example, 16.24% (398/2 451) students had not received animal experiment ethics education and training, 29.46% (722/2 451) were not clear about animal protection laws and regulations, 7.14% (175/2 451) thought animal experiments were immoral; 29.54% (724/2 451) had vague cognition of animal welfare and ethical knowledge; 25.91% (635/2 451) were not familiar with the operation steps; 9.38% (230/2 451) were indifferent to the extra treatment of animals due to operation errors, 7.83% (192/2 451) chose to give up the experiment in the treatment of animals after massive bleeding, only 5.43% (133/2 451) chose to continue the experiment after timely hemostasis and infusion, and 9.26% (227/2 451) chose to do operations unrelated to the experiment. After the experiment, 2.28% (56/2 451) chose to kill the animals by bloodletting, only 5.51% (135/2 451) chose excessive anesthesia euthanasia, and 1.96% (48/2 451) chose to kill the animals by cervical dislocation and violence. Only 15.79% (387/2 451) chose to remember the dead animal for 2 minutes. Only 32.56%(798/2 451) of the respondents understood virtual simulation experiment, 34.92% (856/2 451) of the respondents thought that virtual simulation experiment or experimental teaching video could be used to replace the existing live animal experiment, 77.56% (1 901/2 451) believed that the construction of virtual simulation laboratory should be strengthened.Conclusion:It is imperative to strengthen the education of students' ethics of experimental animals, which is conducive to the establishment of correct ethics of experimental animals for medical students, so that the "3R" principle and animal welfare can be truly implemented in experimental teaching and scientific research experiments.

Objective: 18F-fluorodeoxyglucose (FDG) PET/CT is often used for detecting malignancy in patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH), with acceptable sensitivity but relatively low specificity. The aim of this study was to improve the diagnostic ability of 18F-FDG PET/CT in identifying malignancy in patients with HLH by combining 18F-FDG PET/CT and clinical parameters. Materials and Methods: Ninety-seven patients (age ≥ 14 years) with secondary HLH were retrospectively reviewed and divided into the derivation (n = 71) and validation (n = 26) cohorts according to admission time. In the derivation cohort, 22 patients had malignancy-associated HLH (M-HLH) and 49 patients had non-malignancy-associated HLH (NM-HLH). Data on pretreatment 18F-FDG PET/CT and laboratory results were collected. The variables were analyzed using the Mann-Whitney U test or Pearson’s chi-square test, and a nomogram for predicting M-HLH was constructed using multivariable binary logistic regression. The predictors were also ranked using decision-tree analysis. The nomogram and decision tree were validated in the validation cohort (10 patients with M-HLH and 16 patients with NM-HLH). Results: The ratio of the maximal standardized uptake value (SUVmax) of the lymph nodes to that of the mediastinum, the ratio of the SUVmax of bone lesions or bone marrow to that of the mediastinum, and age were selected for constructing the model. The nomogram showed good performance in predicting M-HLH in the validation cohort, with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.686–0.971). At an appropriate cutoff value, the sensitivity and specificity for identifying M-HLH were 90% (9/10) and 68.8% (11/16), respectively. The decision tree integrating the same variables showed 70% (7/10) sensitivity and 93.8% (15/16) specificity for identifying M-HLH. In comparison, visual analysis of 18F-FDG PET/CT images demonstrated 100% (10/10) sensitivity and 12.5% (2/16) specificity. Conclusion 18F-FDG PET/CT may be a practical technique for identifying M-HLH. The model constructed using 18F-FDG PET/CT features and age was able to detect malignancy with better accuracy than visual analysis of 18F-FDG PET/CT images.

Objective:To explore the value of case analysis combined with role revelation in cultivating thinking ability of surgical nursing training.Methods:A total of 87 newly recruited nurses who needed to rotate in the surgical system of Fenyang Hospital, Shanxi Medical University from January 2019 to October 2020 were selected as the study subjects. They were divided into control group ( n=43) and study group ( n=44). The control group used traditional teaching, and the study group used case analysis combined with role revelation. The clinical thinking ability of nurses was evaluated by written examination of clinical thinking ability and clinical thinking ability score table. SPSS 22.0 was used for t-test. Results:The scores of written examination of clinical thinking ability (history collection, preliminary clinical diagnosis, preliminary nursing measures, auxiliary examination interpretation, comprehensive analysis of diagnosis and treatment process, nursing and discharge diagnosis, and health education) of nurses in the study group were significantly higher than those in the control group ( P<0.05). The scores of clinical thinking ability (critical thinking ability, system thinking ability and evidence-based thinking ability) of nurses in the study group were higher than those in the control group, and the difference was statistically significant ( P<0.05). Conclusion:Case analysis combined with role revelation in the surgical nursing training of new nurses is helpful to improve the trainees' clinical thinking ability.

This article explores the shortcomings and proposes research directions from the overview of mobile medicine and its application in the prevention, self-management, and health education of female stress urinary incontinence, with a view to providing new ideas and methods for the prevention and treatment of female stress urinary incontinence.

Adoptive T-cell therapy is the administration of tumor cytotoxic T-cells derived from either patient himself or donors, which were induced or genetically engineered and expanded, and then injected into patients. Several strategies for adoptive T-cell therapy have been developed since last 30 years. From lymphokine-activated killer cells, tumor-infiltrating lymphocytes, cytokine-induced killer cells, to gene-modified T-cells and tumor associated antigen (TAA)-specific cytotoxic T-cells, the adoptive T-cell therapy has been moving forward to more precise tumor targeting and more effective in elimination of cancer cells. This article reviewed the advances of therapeutic approaches of adoptive T-cell therapy for cancer patients.

Objective To evaluate the effect of targeted monitoring and comprehensive intervention measures on reducing the occurrence of catheter-associated urinary tract infection(CAUTI)in patients in non-intensive care unit(Non-ICU).Methods In quarter 4 of 2015,patients with indwelling urinary catheter in clinical departments were conducted a baseline survey(before intervention),risk factors for CAUTI in patients were analyzed,targeted monitoring programmes and comprehensive intervention measures were initiated in 2016(after intervention),incidence of CAUTI before and after intervention was compared.Results After taking intervention measures,hand hygiene compliance rate increased from 78.51%in quarter 4 of 2015 to 92.99%in quarter 3 of 2016 and 90.73%in quarter 4 of 2016(x2=7.342,3.998,respectively,both P<0.05),the correct disposal rate of patients' urinary catheterization system increased from 72.83%in quarter 4 of 2015 to 95.44%in quarter 4 of 2016(x2=30.267,P<0.05).A total of 12 067 patients with indwelling urinary catheter were monitored,incidence of CAUTI dropped from 1.03%(24/23 313)in quarter 4 of 2015(before intervention)to 0.53%(14/26 595)in quarter 4 of 2016(after intervention),difference was statistically significant(x2=4.126,P=0.042).Conclusion Improving the quality of urinary catheterization system in patients with indwelling catheter through targeted monitoring can effectively reduce the incidence of CAUTI in patients in Non-ICU.

Objective To investigate the effect and mechanism of decorin (DCN) on invasion of colorectal cancer cell line HCT116 in vitro.Methods Transwell assay was employed to detect the invasion of HCT116 cells;Real-time PCR was used to detect the expression of CD133 and TIMP-2 mRNA of HCT116 cells;Western blot method was used to detect the expression of HIF-1α, CD133 and TIMP-2 protein of HCT116 cells.Results 1) When the concentrations of DCN was 0, 1 and 3 mg/L, under the conditions of normal oxygen and hypoxia, the numbers of invasive cells were (241±46), (168±46), (51±17) fields in each well (P<0.01) and (207±61), (213±64), (156±54), (44±17) fields in each well (P<0.01).2) Under the normoxic conditions, the TIMP-2 mRNA and protein in HCT116 cells were increased by DCN (3 mg/L) (P<0.01), but that of CD133 were not affected.3) DCN (3 mg/L) significantly decreased the expression of HIF-1α/CD133/TIMP-2 protein in HCT116 cells under hypoxia (P<0.01), but had no significant effect on the expression of CD133 mRNA.ConclusionsUnder the conditions of hypoxia and normal oxygen, DCN may function through different mechanisms to inhibit the invasion of colorectal adenocarcinoma cell line HCT116 in vitro.

Objective:To study the feasibility of 3-D reconstruction model in the observation of tetrachlorodibenzo-p-dioxin(TCDD) effected palatal organ development of fetal mouse.Methods:Kunming mice treated 40 ug/kg TCDD by lavage on day 12.5 of pregnancy were used as in the experimental group,isodose corn oil treated in the control group.On day 13.5,14.5 and 15.5 of pregnancy heads of the fetal mice were taken out and fixed.Conventional paraffin serial sections of palatal organ were preparated and dyed by hematoxylin-eosin,images of the palatal organs were collected and photoshop treated,3-D reconstruction of the palatal organ was performed by 3D-DOCTOR software.Results:3-D reconstruction images showed that palatal organs moved from on both sides above the tongue and gradually closed and merged in the control group.In the experimental group,the palatal organs moved from on both sides above the tongue was later than control group,gradually closed,but not merged,formed cleft palate.Conclusion:3D-DOCTOR software reconstruction can be used for the study of the development process effected by TCDD in the pregnant mouse.

Objective To explore the influence of corporate governance at public hospitals on their nature of public welfare,in order to provide reference for promoting the reform of public hospital corporate governance.Methods Hypotheses of such impacts were raised by means of literature review. 460 questionnaires were collected from site survey,and four factors of public hospital corporate governance were used as independent variables,and five factors of the public welfare performance as dependent variables,for a correlation analysis and multiple linear regression analysis.Results A clear correlation is found among medical service level,and decision-making mechanism,the mechanism of key employees recruit/evaluation/incentive and their constraints (P < 0.05 ).Completion status of public health services is significantly correlated with the mechanism of recruit/evaluation/incentive and constraint,and their supervision mechanism as well(P <0.05).Medical technology level and cost of medical services are significantly correlated with decision-making mechanism.Conclusions In consideration of public hospital corporate governance,such mechanisms as decision-making,supervision,recruit,evaluation,incentive and constraint for key employees play a key role for public welfare performance.It is recommended to promote the hospital corporate governance reform from the above aspects.