Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Lateral organ boundaries (LOB) domain (LBD) genes encode a family of transcription factors ubiquitous in higher plants, playing crucial roles in the growth, development, and stress responses. Hippophae rhamnoides, known for its drought, cold, and saline-alkali tolerance, offers significant economic benefits and ecological values. Utilizing the whole genome data and bioinformatics approaches, this study identified and analyzed the LBD gene family in H. rhamnoides. Additionally, we examined the expression pattern of HrLBD genes by integrating the transcriptome data from male and female flower buds in development. Eleven LBD genes were identified in H. rhamnoides, and these genes were distributed on five chromosomes. The HrLBD proteins showed the lengths ranging from 159 aa to 302 aa, the molecular weights between 18 249.91 Da and 33 202.01 Da, and the subcellular localization in the nucleus or chloroplasts. LBD protein domains and gene structures were highly conserved, featuring similar motifs. The phylogenetic analysis of HrLBD genes and the LBD genes in Arabidopsis thaliana and Hordeum vulgare revealed that HrLBD genes falled into two major categories: Class Ⅰ and Class Ⅱ. The transcriptome data and RT-qPCR showed that HrLBD genes were highly expressed in male flower buds, with up-regulated expression levels throughout bud development, indicating a role in the specific stage of male flower bud development. This study lays a theoretical foundation for exploring the roles of HrLBD genes in the growth, development, and sex differentiation of H. rhamnoides flower buds.
Flowers/genetics* ; Hippophae/metabolism* ; Phylogeny ; Gene Expression Regulation, Plant ; Plant Proteins/genetics* ; Transcription Factors/genetics* ; Multigene Family ; Genes, Plant

Acute skin failure is a common condition of skin damage in critically ill patients, which seriously affects the prognosis of patients. This article summarizes the evaluation indicators, techniques, and comparison of evaluation indicators and techniques for acute skin failure, in order to provide references for the development of acute skin failure evaluation tools and the formulation of nursing measures.

This paper interprets the background, content overview and characteristics, clinical practice significance and disciplinary development of Nursing Standards for Clinical Operation Techniques in Critical Care Ultrasound (hereinafter referred to as the Standards) and puts forward reflections on the clinical application of the Standards, aiming to improve the critical care ultrasound techniques of clinical nursing staff, solve nursing challenges and make clinical nursing ultrasound techniques more scientific, standardized and homogenized.

Objective:To gain a deep understanding of the current cognition and training needs of nursing undergraduates regarding their emergency response teamwork skills, and to provide reference for the development of courses on emergency response teamwork among nursing undergraduates.Methods:From September to October 2023, purposive sampling was used to select 15 senior nursing undergraduates from Peking Union Medical College, Beijing University of Chinese Medicine, and Beijing City University as subjects for semi-structured interviews. Colazizzi 7-step analysis method was used to summarize and extract themes.Results:Three themes were extracted, including insufficient cognition and skill in emergency response, lack of emergency response teamwork cultivation, and the need for systematic and comprehensive training courses.Conclusions:Universities, hospitals, and other training institutions should work together to develop a systematic emergency response teamwork training course for nursing undergraduates, to cultivate the skills of nursing undergraduates and reserve talents for high-quality emergency response nursing teams.

Objectives To explore the establishment and effects of a multilevel and inter-disciplinary management scheme for specialist nurses.Methods The multilevel and inter-disciplinary management scheme included establishing the pyramid hierarchical training model,exploring superimposed training mechanism for specialist nurses with horizontal expansion,vertical extension,and deep development,and constructing stereoscopic clinical evaluation and quantitative assessment system.Four hundred-forty two specialized nurses have been recruited to join the multilevel and inter-disciplinary management scheme from July 2021 to August 2023.The core competencies of specialized nurses were compared before and after the implementation of management scheme.Results The quality development of specialized nursing have been improved,and the total scores and the scores of 3 dimensions(research innovation,management,and professional development)in core competencies of specialized nurses after the intervention of multilevel and inter-disciplinary management scheme were higher than those before(P＜0.05).Conclusion The multilevel and inter-disciplinary management scheme can effectively improve the core competencies of specialized nurses,and promote the high-quality development of specialized nursing.

Indocyanine Green/therapeutic use* ; Photochemotherapy ; Combined Modality Therapy ; Anti-Infective Agents

To evaluate the clinical effects and pathological characteristics of gastric tumors of fundic gland type treated with endoscopic submucosal dissection (ESD), data of 7 patients who treated by ESD and whose postoperative pathology indicated gastric adenocarcinoma of fundic gland type or gastric oxyntic gland adenoma in Endoscopic Center of Beijing Chao-Yang Hospital of Capital Medical University from August 2018 to June 2022 were collected. The clinical characteristics, surgical complications, preoperative and postoperative pathological data and follow-up data were evaluated. The lesions of the 7 patients were all located at gastric fundus, and were treated by ESD successfully. No bleeding, perforation or other complications occurred during and after the operation. Postoperative pathology showed that tumor cells originated from deep mucosa with an invasive growth pattern. Most of tumor surfaces were covered with normal concave epithelium. Tumors infiltrated into submucosa in 4 patients, and submucosa infiltration depth was more than 500 μm (550 μm) in 1 patient. Immunohistochemistry showed that MUC-6 was diffusely positive, indicating that the tumor originated from the main cell source. The expressions of MUC-2, MUC-5AC, CDX-2, CD10, and CgA were negative in all cases. With the mean follow-up time of 21 months, the ulcer healed well after the operation, with no recurrence. Gastric tumors of fundic gland type have relatively unique biological characteristics, and ESD is the preferred treatment. In addition, the histological characteristics can be used to differentiate from other gastric tumors by immunohistochemistry.

BACKGROUND: Thyroid function abnormality (TFA) is one of the common adverse reactions in patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy, but the risk factors of TFA and its relationship with efficacy are not completely clear. The purpose of this study was to explore the risk factors of TFA and its relationship with efficacy in patients with advanced NSCLC after immunotherapy. METHODS: The general clinical data of 200 patients with advanced NSCLC in The First Affiliated Hospital of Zhengzhou University from July 1, 2019 to June 31, 2021 were collected and analyzed retrospectively. χ² test and multivariate Logistic regression were used to explore the risk factors of TFA. Kaplan-Meier curve was drawn and Log-rank test was used for comparison between groups. Univariate and multivariate Cox analysis was used to explore the efficacy factors. RESULTS: A total of 86 (43.0%) patients developed TFA. Logistic regression analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS), pleural effusion and lactic dehydrogenase (LDH) were factors influencing TFA (P<0.05). Compared with normal thyroid function group, the median progression-free survival (PFS) of patients in the TFA group was significantly longer (19.0 months vs 6.3 months, P<0.001), and the objective response rate (ORR) (65.1% vs 28.9%, P=0.020) and disease control rate (DCR) (100.0% vs 92.1%, P=0.020) of the TFA group were better than those of the normal thyroid function group. Cox regression analysis showed that ECOG PS, LDH, cytokeratin 19 fragment (CYFRA21-1) and TFA were factors influencing prognosis (P<0.05). CONCLUSIONS ECOG PS, pleural effusion and LDH may be risk factors affecting the occurrence of TFA and TFA may be a predictor of the efficacy of immunotherapy. Patients with advanced NSCLC who have TFA after immunotherapy may obtain better efficacy.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; Retrospective Studies ; Thyroid Gland ; Lung Neoplasms/therapy* ; Immunotherapy/adverse effects* ; Pleural Effusion

Objective:To explore the current situation of nursing human caring in hospital wards and analyze its influencing factors, so as to facilitate the development of nursing human caring practice.Methods:From July to November 2022, a total of 107 hospitals were surveyed through stratified convenience sampling method, and 4 072 ward nursing managers were recruited to finish the general information questionnaire and the ward nursing human caring status questionnaire. The general information included the region, class and type of the hospital, etc. The ward nursing human caring status questionnaire included 38 items in 5 dimensions of nursing human caring system and process, humanistic quality and training of nursing staff, humanistic environment and facilities, human caring procedures and measures, and human caring quality evaluation and improvement, with a full score of 190 points. Descriptive statistics were used to analyze the general data, independent samples t-test, ANOVA and correlation analysis were used to analyze the factors influencing the current status of nursing human caring in the ward, while multiple linear regression analysis was used to conduct a multivariate analysis. Results:The score of nursing human caring in hospital wards was 156.91±27.78. Whether the hospital had carried out nursing human caring pilot(demonstration) wards, whether the ward had previously been a hospital nursing human caring pilot(demonstration) nursing unit, the type of ward, and whether nursing managers had participated in human caring training were the influencing factors of the implication of nursing humanistic caring in wards( P<0.05). Conclusions:The practice of nursing human caring in hospital wards is at a good level, but needs to be further strengthened. Nursing managers should take systematically strategies to promote the development of nursing human caring practice.