OBJECTIVES: To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression. METHODS: ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting. RESULTS: ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin. CONCLUSIONS BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
Humans ; Cell Movement ; Transcription Factors/metabolism* ; Esophageal Neoplasms/metabolism* ; Cell Line, Tumor ; Cell Cycle Proteins ; Azepines/pharmacology* ; Epithelial-Mesenchymal Transition ; Carcinoma, Squamous Cell/metabolism* ; Esophageal Squamous Cell Carcinoma ; Triazoles/pharmacology* ; Nuclear Proteins/genetics* ; Cell Proliferation ; Acetyl-CoA Carboxylase/genetics* ; Transfection ; Autophagy ; Bromodomain Containing Proteins

Objective To explore the current status of minor children parenting concerns among young and middle-aged breast cancer patients and investigate the influencing factors based on a random forest model so as to provide references for clinical interventions.Methods A convenience sampling method was used to select breast cancer patients undergoing treatment in our hospital between April and December 2023.A self-designed general information questionnaire,the Chinese version of parenting concerns questionnaire(PCQ),perceived social support scale(PSSS),concern about recurrence scale(CARS),and the brief illness perception questionnaire(BIPQ)were used for the study.A random forest model and the least absolute shrinkage and selection operator(LASSO)were employed to prioritise variables and filtered by significance.The selected variables were then incorporated into the multiple linear regression analysis.Results A total of 260 patients completed the study.The score of minor children parenting concerns of young and middle-aged breast cancer patients was 51.1±6.4.The multiple linear regression analysis,which included variables determined by random forest and LASSO regression(and sorted by the importance of influencing factors),showed that higher disease perception,lower perceived social support,greater concern about cancer recurrence,stage IV tumors,being divorced/widowed,and having more minor children were associated with higher parenting concerns among young and middle-aged breast cancer patients(all P<0.05),accounting for 57.0%of the total variance.Conclusion The minor children parenting concerns in young and middle-aged breast cancer patients are at a moderately high level and are influenced by a variety of factors.Healthcare professionals should develop targeted measures and interventions to reduce the parenting concerns among the patients.

Objective To explore the current status of minor children parenting concerns among young and middle-aged breast cancer patients and investigate the influencing factors based on a random forest model so as to provide references for clinical interventions.Methods A convenience sampling method was used to select breast cancer patients undergoing treatment in our hospital between April and December 2023.A self-designed general information questionnaire,the Chinese version of parenting concerns questionnaire(PCQ),perceived social support scale(PSSS),concern about recurrence scale(CARS),and the brief illness perception questionnaire(BIPQ)were used for the study.A random forest model and the least absolute shrinkage and selection operator(LASSO)were employed to prioritise variables and filtered by significance.The selected variables were then incorporated into the multiple linear regression analysis.Results A total of 260 patients completed the study.The score of minor children parenting concerns of young and middle-aged breast cancer patients was 51.1±6.4.The multiple linear regression analysis,which included variables determined by random forest and LASSO regression(and sorted by the importance of influencing factors),showed that higher disease perception,lower perceived social support,greater concern about cancer recurrence,stage IV tumors,being divorced/widowed,and having more minor children were associated with higher parenting concerns among young and middle-aged breast cancer patients(all P<0.05),accounting for 57.0%of the total variance.Conclusion The minor children parenting concerns in young and middle-aged breast cancer patients are at a moderately high level and are influenced by a variety of factors.Healthcare professionals should develop targeted measures and interventions to reduce the parenting concerns among the patients.

Objective:To develop a homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction.Methods:The preliminary contents of the assessment system were determined through a literature review and expert interviews, and two rounds of questionnaire-based consultation was conducted with 20 experts using the Delphi method. With the use of Excel 2016 and SPSS 26.0, we calculated the coefficient of judgement basis (Ca), the coefficient of familiarity (Cs), the coefficient of authority (Cr), and Kendall's coefficient of concordance ( W ) as well as the mean, standard deviation, and coefficient of variation of all parameters, to identify the specific items and weights for the homogeneous management evaluation system for clinical observership teaching under the background of national first-class discipline construction. Results:In the two rounds of consultation, experts were both 100.00% active in responding to the questionnaires; the coefficients of authority of experts were 0.889 and 0.935, respectively; the coefficients of familiarity were 0.856 and 0.936, respectively; the coefficients of judgment were 0.922 and 0.934, respectively; and Kendall's coefficients of concordance were 0.476 and 0.563, respectively. Finally, 7 first-level items and 21 second-level items were included in the content framework of the homogeneous management evaluation system.Conclusions:The construction process of the homogeneous management evaluation system of clinical observership teaching is complete and reliable, which can provide a reference for the homogeneous management of clinical observership teaching, but further verification and improvement are needed.

【Objective】 To analyze the related factors of emotional and behavioral abnormalities in children with overactive bladder (OAB). 【Methods】 OAB children (aged 6 to 16 years) in a survey of 5 032 children from a county in Henan Province during Sep.2022 and Dec.2022 were identified and surveyed with Overactive Bladder Symptom Score (OABSS), Strength and Difficulties Questionnaire (SDQ) and Pediatric Sleep Questionnaire (PSQ). According to the SDQ score, they were divided into abnormal group (SDQ≥20) and normal group. 【Results】 There were 35.7%(137/385) cases in the abnormal group and 64.3% (248/385) in the normal group. Gender, education level of caregivers, body mass index (BMI), age, constipation, enuresis and severity of OAB were significantly associated with emotional and behavioral abnormalities (P<0.05). Children in the abnormal group showed significant differences in emotional symptoms, conduct problems, hyperactivity symptoms, peer interaction and sleep (P<0.001). Multivariate regression analysis revealed significant differences in gender, educational level of caregi-vers, BMI, age, constipation, enuresis, severity of OAB and PSQI between the two groups (P<0.05). 【Conclusion】 The prevalence of emotional and behavioral abnormalities is high in children with OAB, which is related to female gender, high BMI, puberty, constipation, enuresis and severity of OAB.

Objective To evaluate the effect and mechanism of nicotinamide mononucleotide (NMN) on ischemia-reperfusion injury (IRI) induced by donor liver after cardiac death in rat models. Methods Rat models of orthotopic liver transplantation were established by "magnetic ring + double cuff" method. SD rats were randomly divided into the sham operation group (Sham group), orthotopic liver transplantation group (OLT group), NMN treatment + orthotopic liver transplantation group (NMN group), NMN+sirtuin-3 (Sirt3) inhibitor (3-TYP) + orthotopic liver transplantation group (NMN+3-TYP group), respectively. Pathological changes and hepatocyte apoptosis of the rats were observed in each group. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents in liver tissues were detected. The expression levels of Sirt3, microtubule-associated protein 1 light chain 3 (LC3)Ⅱ, PTEN-induced putative kinase 1 (PINK1), Parkin and translocase of the outer mitochondrial membrane 20 (TOMM20) in liver tissues were measured. Postoperative survival of the rats in each group was analyzed. Results Compared with the Sham group, serum ALT and AST levels were higher in the OLT group. Compared with the OLT group, the levels of ALT and AST were decreased in the NMN group. Compared with the NMN group, the levels of ALT and AST were increased in the NMN +3-TYP group (all P < 0.05). The liver tissue structure of rats in the Sham group was basically normal. In the OLT group, pathological changes, such as evident congestion, vacuolar degeneration and hepatocyte necrosis, were observed in the liver tissues. Compared with the Sham group, Suzuki score and apoptosis rate were higher in the OLT group. Suzuki score and apoptosis rate in the NMN group were lower than those in the OLT group. Suzuki score and apoptosis rate in the NMN+3-TYP group were higher compared with those in the NMN group (all P < 0.05). Compared with the Sham group, the SOD content was decreased, whereas the MDA content was increased in the OLT group. Compared with the OLT group, the SOD content was increased, whereas the MDA content was decreased in the NMN group. Compared with the NMN group, the SOD content was decreased, whereas the MDA content was increased in the NMN+3-TYP group (all P < 0.05). Compared with the Sham group, the relative expression levels of Sirt3 and TOMM20 proteins were down-regulated, whereas those of PINK1, Parkin and LC3Ⅱproteins were up-regulated in the OLT group. Compared with the OLT group, the relative expression levels of Sirt3, PINK1, Parkin and LC3Ⅱproteins were up-regulated, whereas that of TOMM20 protein was down-regulated in the NMN group. Compared with the NMN group, the relative expression levels of PINK1, Parkin and LC3Ⅱproteins were down-regulated, whereas that of TOMM20 protein was up-regulated in the NMN+3-TYP group (all P < 0.05). In the Sham group, the 7 d survival rate of rats was 100%, 50% in the OLT group, 75% in the NMN group and 58% in the NMN+3-TYP group, respectively. Conclusions NMN may enhance the antioxidative capacity of the liver, induce PINK1/Parkin-mediated mitochondrial autophagy, and alleviate IRI of the liver by up-regulating Sirt3, thereby playing a protective role in the donor liver after cardiac death.

Cachexia is a common complication in patients with lung cancer. It aggravates the toxic and side effects of chemotherapy, hinders the treatment plan, weakens the responsiveness of chemotherapy, reduces the quality of life, increases complications and mortality, and seriously endangers the physical and mental health of patients with lung cancer. The causes and pathogenesis of tumor cachexia are extremely complex, which makes its treatment difficult and complex. Controlling cachexia in lung cancer patients requires many means such as anti-tumor therapy, inhibition of inflammatory response, nutritional support, physical exercise, and relief of symptoms to exert the synergistic effect of multimodal therapy against multiple mechanisms of tumor cachexia. To date, there has been a consensus within the discipline that no single therapy can control the development of cachexia. Some therapies have made some progress, but they need to be implemented in combination with multimodal therapy after fully assessing the individual characteristics of lung cancer patients. This article reviews the application of drug therapy and nutritional support in lung cancer patients, and looks forward to the research direction of cachexia control in lung cancer patients.
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Cachexia/therapy* ; Combined Modality Therapy ; Humans ; Lung Neoplasms/drug therapy* ; Neoplasms/complications* ; Nutritional Support/adverse effects* ; Quality of Life

Objective:To explore the effect of health education based on theory of planned behavior combined with stepped care model on negative emotion, psychological flexibility and quality of life in patients with lung cancer undergoing chemotherapy.Methods:From October 2020 to December 2021, 108 chemotherapy patients who underwent lung cancer surgery in Affiliated Hospital of Weifang Medical College and had anxiety or depression that scores was greater than 7 in any dimension of the Hospital Anxiety and Depression Scale (HADS) were selected as the study subjects. The study subjects were divided into observation group ( n=46) and control group ( n=48) by random digits table method. Routine care was implemented in the control group. The observation group implemented health education based on the theory of planned behavior combined with stepped care model intervention. The HADS scale was used every 4 weeks to assess negative emotion in both groups. In observation, patients with negative emotion relief stop the next stage of nursing intervention, and patients without relief continue the next stage of higher intensity nursing intervention. Results:Before the intervention, there were no significant difference in the scores of negative emotion, psychological flexibility and quality of life between the two groups ( P>0.05). After intervention, the scores of all dimensions of negative emotion and the total score in the observation group were significantly lower than those in the control group, and the differences had statistical significance ( t=4.86, 3.19 and 4.53, all P<0.05). After the intervention the scores of psychological flexibility and quality of life dimensions and the total score in the observation group were higher than those in the control group, the differences had statistical significance (t values were -6.01--2.89, all P<0.05). After the intervention, there was no significant difference in the remission rate of negative emotions between the clinical observation stage of the observation group and the concurrent control group ( P>0.05). The remission rates of guided self-help, problem-solving therapy, psychological or drug therapy and total negative emotions in the observation group were 38.46%(15/39), 33.33%(8/24), 6/16 and 78.26%(36/46), respectively, which were higher than those in the control group, and the differences had statistical significance ( χ2 values were 7.04 - 13.80, all P<0.05). Conclusions:Health education based on the theory of planned behavior combined with stepped care model can effectively alleviate the negative emotions of lung cancer patients undergoing chemotherapy and improve psychological flexibility and quality of life.

Liver transplantation is an effective treatment of end-stage liver diseases. However, liver ischemia-reperfusion injury (IRI) and rejection significantly cause the decrease of survival rate of liver graft. Therefore, it is urgent to explore a novel method, which can not only alleviate liver IRI, but also promote immune tolerance of allograft, thereby improving the survival rate of liver graft. Extracellular vesicle (EV) is nanoparticle released from cells into the extracellular microenvironment, which may alleviate graft injury by repairing autophagy, immunosuppression and accelerating tissue regeneration. Hence, EV becomes a research hot spot in the field of liver transplantation. Nevertheless, the clinical application of EV encounters multiple challenges, such as separation, purification, identification, storage of EV and how to deliver EV to the target cells. In this article, the mechanism of EV in liver IRI, the challenges in clinical application of EV and the potential application of EV were reviewed, aiming to provide reference for the clinical application of EV in liver transplantation.

Objective:To explore awareness of self-body image and sexual experience of patients after breast cancer surgery in the Internet era, so as to provide reference for clinical nursing staff to implement targeted intervention.Methods:This research adopted phenomenological research methods in qualitative research. A total of 15 patients with breast cancer after surgery who were admitted to Department of Breast Surgery in a ClassⅢ Grade A hospital in Weifang of Shandong Province from March to August 2020 were selected as the research objects by the purposive sampling method. Face-to-face semi-structured in-depth interviews were conducted with them, and Colaizzi's 7-step method was applied for data analysis.Results:A total of 4 themes were extracted, namely, self-image disorder, poor quality of sexual life and impaired mental health; poor health literacy and lack of disease-related knowledge; different effective coping strategies and desire for all-round support.Conclusions:Clinical nursing staff should pay close attention to the body image awareness and sexual experience of patients after breast cancer surgery and take targeted intervention measures to enable patients to treat their bodies correctly, help them to establish a correct sexual attitude and promote their physical and mental health. At the same time, with the Internet as the carrier and artificial intelligence as the realization tool, it will play the role of artificial intelligence in the prevention, diagnosis, treatment and rehabilitation of breast diseases, and provide patients with high-quality, convenient and efficient services.