OBJECTIVES: To investigate the role of DTX2 in regulating biological behaviors of oxaliplatin-resistant colorectal cancer cells (CRC/OXA cells). METHODS: CCK8 assay was used to determine the inhibition rate of oxaliplatin-treated CRC cells. A CRC/OXA cell line was constructed, in which DTX2 expression level was detected. The cells were transfected with a DTX2-shRNA plasmid or co-transfected with DTX2-shRNA and pcDNA-Notch2, and the changes in cell proliferation, migration and invasion ability were evaluated using plate cloning assay, scratch assay and Transwell invasion assay. The expression levels of Notch2, NICD and epithelial-mesenchymal transition (EMT) proteins of the transfected cells were detected with Western blotting. In a nude mouse model bearing SW620/OXA cell xenografts, the effects of DTX2 knockdown and Notch2 overexpression in the implanted cells on tumor growth and protein expressions were tested. RESULTS: The IC₅₀ of oxaliplatin was 6.00 μmol/L in SW620 cells and 8.00 μmol/L in LoVo cells. CRC/OXA cells showed a significantly increased expression of DTX2. DTX2 knockdown in CRC/OXA cells significantly inhibited cell proliferation, migration and invasion, and these effects were reversed by co-transfection of the cells with pcDNA-Notch2. DTX2 knockdown significantly reduced the expression levels of Notch2, NICD and vimentin proteins and increased E-cadherin expression in CRC/OXA cells, and co-transfection with pcDNA-Notch2 potently attenuated the changes in these proteins. In the tumor-bearing mice, DTX2 overexpression obviously promoted the growth of SW620/OXA cell xenograft, enhanced the protein expressions of Notch2, NICD and vimentin, and lowered the expression of E-cadherin. CONCLUSIONS High expression of DTX2 promotes proliferation, migration, invasion and EMT of CRC/OXA cells through the Notch2 signaling pathway, suggesting the potential of DTX2 as a target to improve the efficacy of oxaliplatin.
Epithelial-Mesenchymal Transition ; Humans ; Cell Proliferation ; Oxaliplatin ; Colorectal Neoplasms/metabolism* ; Animals ; Drug Resistance, Neoplasm ; Receptor, Notch2/metabolism* ; Cell Line, Tumor ; Mice, Nude ; Cell Movement ; Organoplatinum Compounds/pharmacology* ; Neoplasm Invasiveness ; Mice

OBJECTIVE Aimed to comprehensively evaluate various immunological changes in a mouse model of eosinophilic chronic rhinosinusitis with nasal polyps(ECRSwNP)induced by ovalbumin(OVA)combined with Aspergillus protease(AP),including nasal polyps-like lesions,subepithelial collagen deposition,inflammatory cell infiltration,epithelial barrier function,and olfactory neuron damage.METHODS C57BL/6 mice were challenged with OVA and AP for 12 weeks.Hematoxylin-eosin(HE),periodic acid-Schiff(PAS),and Masson staining were used to observe the changes of nasal polyps-like lesions,goblet cell hyperplasia,and subepithelial collagen deposition.Immunohistochemistry staining(IHC)was employed to detect the changes of various inflammatory cells,olfactory neurons,and the expression of epithelial tight junction proteins in the nasal and sinus mucosa.RESULTS Compared to the control group,the OVA and AP group showed significantly increased epithelial thickness,noticeable nasal polyps-like lesions,marked subepithelial collagen deposition,and goblet cell hyperplasia in the nasal and sinus mucosa.IHC results revealed a significant increase in eosinophils,along with higher numbers of neutrophils,mast cells,and CD4+T cells in the OVA and AP group.Additionally,the expression of tight junction proteins ZO-1 and E-cadherin in the nasal and sinus mucosa and the area of OMP+olfactory neurons in the olfactory epithelium were significantly lower in the OVA and AP group compared to the control.CONCLUSION Continuous exposure to OVA combined with AP successfully induces ECRSwNP.The establishment of this model provides a foundation for further research into the pathogenesis and the evaluation of new therapeutic strategies for ECRSwNP.

Chronic sinusitis with nasal polyps(CRSwNP)is a highly heterogeneous chronic inflammatory disease,that persistently impacts patients'quality of life.To date,its etiology and pathogenesis remain incompletely unclear.Animal models serve as crucial tools for exploration of CRSwNP pathogenesis However,there is still a lack of a recognized mature and stable mouse model of CRSwNP in basic research.The stable mouse model of CRSwNP has become a key bottleneck in the analysis of the pathogenesis.This paper systematically reviews existing construction methodologies,inflammatory phenotypes,and applicability of murine CRSwNP models.By comparing their advantages and limitations,we will explore future optimization directions.This review will provide a theoretical basis and foundation for the basic research and clinical precision treatment of CRSwNP.

Objective:To investigate the impact of the deep-learning-based CT fractional flow reserve (CT-FFR) on clinical decision-making and long-term prognosis in patients with obstructive coronary heart disease.Methods:In this single-center retrospective cohort study, consecutive patients with obstructive coronary heart disease (with at least one stenosis≥50%) on their first coronary computed tomography angiography (CCTA) in Beijing Anzhen Hospital from February 2017 to July 2018 were included. Baseline clinical and CT characteristics were collected. Deep-learning-based CT-FFR and Leiden CCTA risk score were calculated. All patients enrolled were followed up for at least 5 years. The study endpoint was major adverse cardiovascular events (MACE), defined as the composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and unplanned revascularization. Receiver operating characteristic (ROC) curves were drawn to define the optimal cut-off point of the Leiden score in predicting the 5-year MACE, and survival analysis and Cox regression were performed to explore the related factors of MACE.Results:A total of 622 patients, aged 61 (54, 66) years, with 407 (65.4%) males were included. Diagnostic coronary angiography was performed in 78 patients after their baseline CCTA, with 34 (43.6%) patients had CT-FFR>0.80. During a follow-up time of 2 181 (2 093, 2 355) days, 155 patients (24.9%) suffered from MACE. ROC derived optimal cut-off point of Leiden score for predicting MACE was 15.48. Survival analysis found that male patients, Leiden risk score>15 and CT-FFR≤0.80 had worse prognosis. Multivariate Cox regression analysis identified CT-FFR≤0.80 as an robust and independent predictor of MACE ( HR=4.98, 95% CI 3.15-7.86, P<0.001). Conclusion:Deep-learning-based CT-FFR aids in clinical decision-making and the evaluation of long-term prognosis in patients with obstructive coronary heart disease.

Objective:To summarize the best evidence for the prevention and management of oral mucosal pressure injury (OMPI) in severe neurological patients with tracheal intubation.Methods:The clinical decisions, guidelines, expert consensus, evidence summary, systematic reviews, and clinical practice regarding the prevention and management of OMPI in severe neurological patients with tracheal intubation were searched in domestic and foreign databases, guideline websites, and professional association websites. The search period was from database establishment to May 30, 2023. Four researchers who undergone systematic evidence-based training conducted literature quality evaluation and evidence extraction.Results:A total of 15 articles were included, including three evidence summaries, three systematic reviews, two guidelines, three clinical practices, three expert consensus, and one clinical decision. A total of 27 pieces of best evidence were summarized from six aspects of risk assessment, oral mucosal assessment, oral nursing, tracheal intubation management, nutritional support, and organizational training.Conclusions:The best evidence for the prevention and management of OMPI in severe neurological patients with tracheal intubation summarized provides evidence-based evidence for medical and nursing staff to prevent and manage OMPI in severe neurological patients with tracheal intubation.

Objective:To investigate the past continuing medical education (CME) in pediatrics for general practitioners in community health centers in Longhua District, Shenzhen, so as to explore the willingness, needs and suggestions of general practitioners for CME in pediatrics.Methods:A mixed methods research were used in this study. Firstly, the purpose sampling method was used to select general practitioners in community health centers in Longhua District, Shenzhen for personal in-depth interviews. The interview contents were recorded and transcribed. The interview contents were coded by NVivo software. Theme frame analysis method was used for data sorting and theme extraction. Based on the results of qualitative interviews, the questionnaire was developed and distributed through the electronic questionnaire platform, and relevant questionnaire data were analyzed by Excel.Results:The results of qualitative research showed that after personal in-depth interviews with 10 general practitioners, the information reached saturation. Through repeated reading, induction and analysis of the interview data, four themes were extracted: ① previous pediatric training opportunities and satisfaction; ② willingness to participate in pediatric training; ③ the demand of training content, form and duration; ④ measures to encourage participation in training. In terms of quantitative research results, a total of 223 electronic questionnaires were collected, among which there were 219 valid questionnaires. Besides, 150 (68.5%) general practitioners said that they had no or only a few training opportunities in pediatrics CME in the past. There were some problems in the past CME training, such as unsystematic training (39 practitioners, 66.1%), narrow course coverage (30 practitioners, 50.8%), the content divorced from clinical practice (29 practitioners, 49.2%), monotonous teaching method (27 practitioners, 45.8%), etc. And 210 (95.9%) general practitioners were willing to participate in pediatric training, and 161 (73.5%) hoped that the form of training would be a combination of online and offline. In terms of pediatrics specialty content training needs, the general practitioners had higher demand for respiratory (188 practitioners, 85.8%), digestive (160 practitioners, 73.1%), infectious (145 practitioners, 66.2%) and dermatology (136 practitioners, 62.1%) specialty.Conclusion:There are still some problems in pediatrics CME, such as few training opportunities, unsystematic training, etc. In the future, we need to formulate systematic training plans and incentive measures according to the needs of general practitioners, to strengthen the pediatric professional training for general practitioners and improve their ability to receive children, in order to promote the implementation of hierarchical medical system for children.

Objective:To develop an online continuing education course of pediatrics for primary physicians using the ADDIE model and to evaluate its application effect.Methods:Experts in fields of general practice and pediatrics were invited to develop an online continuing education course of pediatrics for general practitioners using ADDIE model from June to July 2020. From August 2020 to September 2020 the course was conducted with 12 live sessions on the open platform. In September 2020, 16 primary pediatricians and 15 general practitioners who completed whole courses were invited to attend focus group interviews. The interview contents were recorded, transcribed, and coded using Nvivo software; the subject frame analysis method was used to sort the data and refine the theme.Results:Information was saturated by focus group interviews with 14 general practitioners and 14 pediatricians. Finally, three themes were extracted from the interview results:(1)The advantages of this course were practicality, comprehensiveness and online teaching; (2) The course improved the diagnosis and treatment ability of participants, increased self-confidence of doctors and satisfaction of patients, and also promoted academic exchanges among colleagues; (3) For future improvement of the course, the clinical knowledge points, practical procedures, new thinking of diagnosis and treatment, progress in guidelines, and knowledge depth should be added; and the use of case teaching and combination of online with offline, and extending teaching time should be considered.Conclusion:An online continuing education course of pediatrics for primary physicians has been developed based on the ADDIE model, which received favorable feedback from the primary pediatricians and general practitioners who attended the course.

Objective:To investigate the status quo and related issues of reception of pediatric patients by general practitioners in community health centers in Longhua District of Shenzhen through qualitative and quantitative studies.Methods:In qualitative study, 10 general practitioners (GPs) from community health centers in Longhua District of Shenzhen were selected by the purpose sampling method for personal in-depth interviews. The interview contents were recorded and transcribed, then coded by Nvivo software. Theme frame analysis method was used for data sorting and theme extraction. Based on the results of qualitative interviews, the questionnaire was developed and distributed through the electronic questionnaire platform. The contents of the questionnaire included general information, the situation of pediatric patient reception in community health centers, the willingness and ability of GPs to receive children, the existing problems and the measures to promote receiving pediatric patients in community health centers.Results:The results of personal in-depth interviews with 10 GPs showed that the obtained information reached saturation. Through repeated reading, induction and analysis of the interview data, four themes were extracted: ① GPs in community health centers received a large number of pediatric outpatients with common diseases; ② GPs in community health centers are willing to receive child patients, but they were lack of ability; ③ there were many problems of pediatric patients reception in community health centers; ④ training and incentive policies would help to promote child patient reception in community health centers. A total of 223 electronic questionnaires were collected, 219 of which were valid for analysis. All the community health centers in Longhua District received pediatric patients, the number accounted for 20%-60% of the total outpatients; 84.5%(185/219)of the responders were willing to receive child patients, 65.8% (144/219)of them assumed that the consulting ability was average. The main problems for GPs to receive pediatric patients were "insufficient training" (76.7%,168/219) and "lack of consulting ability" (55.3%,121/219). The important measures to promote GPs to receive child patients were to improve their own clinical competence (94.1%,206/219), to have clinical faculty with pediatric background mentoring at the community health center (74.9%,164/219), to improve the supporting facilities (42.9%,94/219) and continuous professional support (38.8%,85/219).Conclusion:The status quo of pediatric patient reception in the community of Shenzhen Longhua District is generally satisfactory. The main problems in this aspect are insufficient training for general practitioners and lack of clinical competence, which should be strengthened and improved in the future.

Objective:To search, evaluate and summarize the evidence of the safety and application of closed tracheal suction systems and to provide reference for clinical nursing work.Methods:BMJ Best Practice, UpToDate, Joanna Briggs Institute Evidence-based Health Care Center, Guidelines International Network, National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, Registered Nurses' Association of Ontario, American Assocition for Respiratory Care, Society of Critical Care Medicine, Medlive, Cochrane Library, PubMed, Embase, CINAHL, CNKI, Wanfang Database, China Biology Medicine disc were searched for related guidelines, system reviews, expert consensus, best practices, etc. The retrieval time was from the database construction to February 28, 2021. Two researchers independently evaluated the quality of the included literature and extracted and summarized the evidence of the literature that met the quality standards.Results:A total of 20 literatures were included, including 3 clinical decisions, 2 guidelines, 11 systematic reviews and 4 expert consensuses. A total of 27 pieces of best evidence were compiled from five aspects, including indications for use, clinical effects, safety, methods of use and replacement.Conclusions:This study summarizes the best evidence on the clinical application of closed sputum suction devices in adults. When applying the evidence, clinical nurses need to select the best evidence in combination with the clinical environment to standardize the clinical application of closed tracheal suction systems.

Objective: To investigate the awareness of sexuality education knowledge in kindergarten teachers in rural areas of Sichuan and its influencing factors, and to provide a scientific basis for sex education capacity improvement among rural teachers. Methods: With multi stage stratified cluster sampling method, 162 teachers selected from 16 rural kindergartens in rural areas of Sichuan Province to conduct questionnaires related to early childhood sex education. Results: The awereness of early childhood sex education foreskin care in rural areas in Sichuan was 73.8%. Knowledge regarding foreskin care(58.8%)", "the function of the family includes rest and entertainment functions(65.6%)", "girls need to clean the reproductive truets from the front to back (68.8%)". Multivariate non conditional Logistic regression analysis results showed that teaching experience>4 years(OR=4.16, 95%CI=1.74-9.98), notice of young children with sexual related behaviors(OR=2.97, 95%CI=1.19-7.40), the number of sources of sexual knowledge sources ≥5(OR=3.39, 95%CI=1.42-8.13) were associated with high awareness of preschool sex education knowledge. Conclusion The preschool sex education knowledge awareness among Sichuan rural kindergarten teachers needs to be improved. A variety of sex education channels should be constructed to encourage teachers, especially those who are newly employed, to acquire more relevant knowledge, pay attention to children’s sex related behaviors, and improve their ability in sex education.