In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

Objective: To understand classroom environmental conditions and their association with spinal curvature abnormalities among students of primary and secondary schools in Guizhou Province, so as to provide a basis for formulating school health policies and scientific prevention and control measures for abnormal spinal curvature in students. Methods: Using a stratified random sampling method, 471 schools (2 811 classrooms) were selected annually across the province from 2022 to 2024 in order to monitor and evaluate classroom environment according to national standards. Spinal examinations were conducted for 196 606 (2022), 194 876 (2023), and 195 048 (2024) students, and χ 2 test was used to analyze the correlation of desk and chair compliance with student spinal curvature abnormalities. Results: The qualified rates of classroom blackboard illuminance uniformity ( 85.41 %) and the blackboard size (82.24%) were the highest in primary and secondary schools in Guizhou Province, while the average blackboard surface illumination qualified rate (20.10%) was the lowest. The average desk illumination (50.11%-58.63%), desk illumination uniformity (61.92%-72.27%) and qualified noise rate (50.04%-51.94%) increased significantly in 3 years; in addition, the compliance rate of desks and chairs decreased from 25.00% to 13.52%, and the differences were all statistically significant ( χ 2=42.48, 80.93, 46.09, 129.72, all P <0.05). Middle school classrooms outperformed primary schools in terms of per capita area, average blackboard illuminance, blackboard illuminance uniformity, average desktop illuminance, desktop illuminance uniformity, and noise compliance ( χ 2=311.55, 12.41, 20.64, 40.76, 10.25, 52.47), but had lower compliance for blackboard size and reflectance ( χ 2=537.29, 7.59) (all P <0.01). Urban schools had higher compliance than suburban schools for per capita area, average blackboard illuminance, average desktop illuminance, and desktop illuminance uniformity ( χ 2=73.71, 17.68, 29.30 , 36.03), but lower compliance for desk-chair suitability, blackboard size, and blackboard reflectance ( χ 2=4.72, 26.02, 5.43 ) (all P <0.05). The spinal curvature abnormality detection rate was 0.83%. A significant association was found between abnormality detection and desk-chair non compliance ( χ 2=223.85, P <0.01). Conclusions Classroom environment hygiene in Guizhou schools is suboptimal. Strengthening school environmental hygiene infrastructure and greater attention to its impact on student s health are essential.

Objective: To understand the epidemiological characteristics of abnormalities spinal curvature among children and adolescents in Karst landform in Guizhou Province, so as to provide a scientific basis for targeted comprehensive intervention. Methods: From September to December 2023, 194 875 children and adolescents aged 6-18 were selected from all countieldistricts of 9 cities (prefectures) in Guizhou Province by stratified random cluster sampling method according to the proportion of Karst landform area in Guizhou Province for carrying out spinal curvature abnormality screening, and a questionnaire survey was conducted on 139 449 students in the fourth grade and above of primary school. Binary Logistic regression was used for multivariate analysis. Results: The detection rate of abnormal spinal curvature among children and adolescents aged 6-18 in Guizhou Province was 1.13%. The detection rates of abnormal spinal curvature in areas with a high proportion of Karst landform, areas with a low proportion of Karst landform, intercalation areas, and nonKarst landform areas were 1.10%, 2.00%, 0.90%, and 0.60%, respectively. Among them, the detection rates of abnormal spinal curvature in female students (2.40%, 1.60%, 0.90%) in areas with a low proportion of Karst landform, intercalation areas and nonKarst landform were higher than those in male students (1.60%, 0.10%, 0.30) (χ2=12.66, 112.69, 30.22, all P<0.05). The detection rates of abnormal spinal curvature among senior high school students (2.00%, 4.30%, 1.40%, 1.30%) in different Karst landform distributions were successively higher than those among junior high school students (1.40%, 3.20%, 1.00%, 0.60%) and primary school students (0.70%, 0.80%, 0.60%, 0.30%) (χ2=306.11, 175.80, 14.24, 39.57, all P<0.05). The results of multivariate Logistic regression analysis showed that the detection rates of abnormal spinal curvature in both highproportion and lowproportion Karst landform areas were higher than those in nonKarst landform areas [OR(95%CI)=1.84(1.05-2.25), 1.60(1.23-2.09), both P<0.05]. Conclusion The detection rate of abnormal spinal curvature in children and adolescents aged 6-18 in Guizhou Province is related to the distribution of Karst landform, so it is necessary to strengthen screening and appropriate comprehensive interventions.

Objective:To analyze the self-evaluation and training needs of standardized parents from pediatric nurses after participating in the standardized residency training of pediatrics, and to explore the feasibility of pediatric nurses as standardized parents and the methods of training and management.Methods:A self-made questionnaire was used to investigate the self-evaluation, the influencing factors, the needs of training content and training form of standardized parents of pediatric nurses. Data analysis was made by SPSS 24.0 statistical software.Results:A total of 37 questionnaires were collected from the standardized parents of nurses. Among them, 36 nurses (97.30%) thought they were very competent for the work of standardized parent; 36 ones (97.30%) thought the most satisfied with their own was responsibility and fairness; 26 ones (70.27%) thought the least satisfied with their own was performance ability; 23 ones (62.16%) thought that the assessment of non-professional diseases would affect their performance in the assessment process; 34 people (91.89%) had the highest demand for training in the contents and skills of consultation; 16 ones (43.24%) thought that "teaching" and "giving cases to doctors and standardized parents for assessment simulation exercise" were the better training methods. Nurses used their own time to participate in training and assessment, and were willing to participate in the certification assessment of standardized parents.Conclusions:In the training of standardized parents of pediatric nurses, it is need to strengthen the training of various abilities, further improve the training contents and forms, reasonably arrange the training and assessment time, and increase policy support to make the standardized parent management of nurses more standardized.

Objective:To analyze the evaluation of the application effect and deficiency of nurses acting as standardized parents in the graduation examination of standardized residency training of pediatrics and further improve and promote the level of standardized parents.Methods:A questionnaire survey was used to collect the scores of nurse standardized parents by students and examiners who took part in the graduation examination of standardized residency training of pediatrics in 2021. And the self-evaluation scores of standardized parents were collected. Counting data were represented by the number of cases and composition ratio. A Chi-square test was used to compare the rates.Results:A total of 125 questionnaires from students and 37 questionnaires from nurse standardized parents were collected, and the overall satisfaction (very satisfied + satisfied) of standardized parents reached 121 (96.80%). In the three dimensions of simulation ability, compliance with question-and-answer rules, and simulated attitude, students believed that the consistency between standardized parents and actual parents in simulated altitude was lower than that in the simulation ability and compliance with question-and-answer rules ( P=0.007, P=0.001). The overall satisfaction of standardized parents (very satisfied + satisfied) reached 87.38% (388/444). There were 26 (70.27%) nurse standardized parents who had the lowest satisfaction with their own performance ability, followed by 28 (75.68%) cases of imitation ability and 30 (81.08%) cases of adaptability. Conclusions:It is feasible to adopt nurse standardized parents in the assessment of standardized residency training of pediatrics, and both students and examiners have higher satisfaction. The next step is to improve the training of nurses standardized parents in the attitude of simulation and, at the same time, enhance the training of imitation ability and adaptability, so as to further expand the construction of standardized parents.

Objective:To explore the relationship between the perceived stress and the independent learning ability of nursing undergraduates, to establish a chain mediation model to investigate the role of psychological capital and self-control in the relationship between the two, aiming to provide a new direction for nursing educators to improve the independent learning ability of nursing undergraduates.Methods:Using the convenient sampling method, a total of 913 nursing undergraduates from 10 universities in Shaanxi Province were selected as research objects from February to March 2023. Perceived Stress Scale (PSS), Positive Psychological Capital Questionnaire (PPQ), Self-control Scale (SCS) and Self-directed Learning Ability Scale (SLAS) were used to investigate the nursing undergraduates.Results:A total of 913 questionnaires were sent out in this study, and 900 were effectively collected, with an effective recovery rate of 98.58% (900/913). The total SLAS score of 900 nursing undergraduates was (87.12±9.20). The perception of stress among undergraduate nursing students could directly predict their self-directed learning ability negatively ( P<0.01), or indirectly affected their self-learning ability through psychological capital and self-control ( P<0.05). Psychological capital (indirect effect value=-0.160) and self-control (indirect effect value=-0.106) played a mediating role between stress perception and self-directed learning ability, and the mediating effect accounted for 38.55% and 25.54%, respectively. Moreover, psychological capital and self-control also played a chain mediating role (indirect effect value=-0.053), and the proportion of chain mediated effect was 12.77%. Conclusions:Perceived stress, psychological capital and self-control are important influencing factors on the self-directed learning ability of nursing undergraduate students. Perceived stress not only directly affects the self-directed learning ability of nursing undergraduate students, but also indirectly affects their self-directed learning ability through the chain mediation effect of psychological capital and self-control.

Objective:To observe the effect of Xuebijing injection on sepsis combined with acute gastrointestinal injury (AGI), and analyze the risk factors of sepsis combined with AGI.Methods:A retrospective cohort study was conducted. Patients with non-gastrointestinal origin admitted to the department of intensive care medicine of the First Hospital of Qinhuangdao from May 1, 2021 to October 30, 2023 were enrolled. The baseline data, source of sepsis infection, vital signs, acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), laboratory tests, comorbidities, interventions during treatment, and the 28-day prognosis were collected. The patients were divided into Xuebijing group and non-Xuebijing group according to whether Xuebijing injection was used or not. According to whether AGI was merged or not, patients were divided into merged AGI group and non-merged AGI group. The main observational indexes were the difference in the incidence of AGI between the Xuebijing group and non-Xuebijing group and the difference in the magnitude of the decline in procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count (WBC) at 7 days after admission, and the difference in the 28-day morbidity and mortality. Risk factors for AGI in septic patients were explored by univariate analysis, and statistically significant indicators were screened and included in binary Logistic regression analysis to determine independent risk factors.Results:A total of 129 patients with sepsis of non-gastrointestinal origin were enrolled, including 57 patients in the Xuebijing group and 72 patients in the non-Xuebijing group. Among 129 patients, 80 patients in the merged AGI group and 49 patients in the non-merged AGI group. There were no statistically significant differences between Xuebijing group and non-Xuebijing group in gender, age, body mass index (BMI), underlying disease, source of infection, vital sign, APACHEⅡscore, SOFA score, and clinical intervention, and there were no statistically significant differences in laboratory tests except for aspartate aminotransferase (AST) and blood urea nitrogen (BUN). The incidence of AGI was significantly lower in the Xuebijing group than that in the non-Xuebijing group [50.87% (29/57) vs. 70.83% (51/72), P < 0.05], and the 28-day mortality was slightly lower than that in the non-Xuebijing group [24.56% (14/57) vs. 30.56% (22/72), P > 0.05]. In the Xuebijing group, the decreases in CRP, PCT and WBC at 7 days after admission were greater than those in the non-Xuebijing group, with statistically significant differences in the decreases of CRP and PCT [CRP (mg/L): 47.12±67.34 vs. 7.76±111.03, PCT (μg/L): 14.08 (-1.22, 50.40) vs. 2.94 (-1.27, 14.80), all P < 0.05]. Univariate analysis showed that the use of acid suppressants, the use of analgesic sedation, the non-use of Xuebijing injections, pulmonary infections, and urinary tract infections were the risk factors for the development of AGI in patients with sepsis. Binary Logistic regression analysis further showed that the use of acid suppressants [odds ratio ( OR) = 2.450, 95% confidence interval (95% CI) was 1.021-5.883, P = 0.045], use of analgesic sedatives ( OR = 2.521, 95% CI was 1.074-5.918, P = 0.034), and urinary tract infection ( OR = 4.011, 95% CI was 1.085-14.831, P = 0.037) were independent risk factors for sepsis combined with AGI, in which the use of Xuebijing injection was a protective factor ( OR = 0.315, 95% CI was 0.137-0.726, P = 0.007). Conclusions:Xuebijing injection reduced the incidence of AGI in patients with non-gastrointestinal sepsis. PCT and CRP decreased more markedly than in patients who did not use Xuebijing injection. The use of acid-suppressing agents, analgesic and sedative agents, and urinary tract infections were independent risk factors for sepsis in combination with AGI, while the use of Xuebijing injection is a protective factor.

Objective:To investigate the clinical features of patients with chronic obstructive pulmonary disease (COPD) and serum-positive specific IgE (SIgE).Methods:This study was a retrospective cohort study. A total of 105 stable COPD patients with allergic features and completed serum SIgE testing were included, and all of them were from Capital Medical University, Beijing Tong Ren Hospital from September 2022 to October 2023. Those with at least one positive result of SIgE testing were classified as positive SIgE COPD group, and those with negative SIgE were classified as negative SIgE COPD group. There were 32 cases (30.5%) in the positive SIgE COPD group and 73 cases (69.5%) in the negative SIgE COPD group. Differences in laboratory tests, pulmonary function, chronic obstructive pulmonary symptom scores, incidence of severe acute exacerbation events in the past year, and drug therapy were compared between the two groups. The risk factors for positive SIgE COPD were analyzed, and the best predictive value for the diagnosis of positive SIgE COPD was analyzed using the area under the curve (AUC) of receiver operating characteristic (ROC).Results:Compared with the negative SIgE COPD group, the percentage of positive SIgE COPD group with rhinitis, sinusitis, sinusitis with nasal polyps, eczema, and a history of drug or food allergy were higher (all P<0.05) and the percentage of those who had quit smoking were higher ( P<0.05); the percentage of IgE above normal thresholds, the level of IgE, the percentage of peripheral blood eosinophil (EOS%), the count of EOS, and fractional exhaled nitric oxide (FeNO) were higher (all P<0.05), and the percentage of those who had severe and above severe Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) pulmonary function classification were higher, while the percentage of forced expiratory volume in one second (FEV 1% predicted), 25% maximal expiratory flow (MEF 25%) and MEF 75/25% were lower, and FEV 1/FVC was higher (all P<0.05). The positive SIgE COPD group had higher modified British medical research council (mMRC) scores and COPD assessment test (CAT) scores, and a higher incidence of severe acute exacerbation events over the past year (all P<0.05), and the use of short-acting β 2 receptor agonists (SABA) or short-acting muscarinic antagonist (SAMA), inhaled corticosteroid (ICS), theophylline and oral hormone therapy were more frequent (all P<0.05). EOS% ( OR=1.252, 95% CI: 1.039-1.508) was a risk factor for SIgE positivity in COPD ( P<0.05), and having quit smoking ( OR=0.385, 95% CI: 0.197-0.751) was a protective factor ( P<0.05). The AUC value of the ROC curve of EOS%>2.5% for the diagnosis of SIgE positivity was 0.647 (95% CI: 0.543-0.752), with a sensitivity and specificity of 52.8% and 73.1%, respectively. Conclusions:Positive SIgE COPD has sever clinical symptoms, high risk of acute exacerbation and deficiencies in treatment. The elevate of EOS% is a risk factor for the development of positive SIgE in COPD patients; positive SIgE COPD meets the diagnostic criteria for allergic COPD phenotype, and EOS% over 2.5% is suggestive of the clinical detection of allergic COPD phenotype.

Objective:To investigate the effect of macrophage-derived exosomes on the morphological transformation of Candida albicans (CA), and to explore the underlying mechanisms.Methods:In vitro cultured human acute monocytic leukemia cell line THP-1 was induced and differentiated into M0 macrophages using the phorbol ester PMA. CA was activated and prepared as the fungal suspension. M0 macrophages were infected with the CA suspension, and the process of cell phagocytosis was observed under a high-content imaging analysis system. M0 macrophage-derived exosomes (exosome group) and CA-infected M0 macrophage-derived exosomes (CA exosome group) were extracted by differential centrifugation; transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis were performed to identify and compare exosomes in the two groups. The exosomes from the two groups were separately co-cultured with CA (exosome-treated group and CA exosome-treated group), and independently cultured CA served as the blank control group; the morphological changes of CA were observed under an inverted microscope, the intracellular cyclic adenosine monophosphate (cAMP) contents were detected by the enzyme-linked immunosorbent assay (ELISA), and the expression levels of cAMP-related genes, RAS1 and CDC35 (also known as Cyr1), were detected by real-time quantitative PCR (RT-qPCR) . Results:Western blot analysis showed that exosomes from the exosome group and CA exosome group both expressed the tumor susceptibility gene 101 protein (TSG101, an exosome marker), and did not express calnexin (a negative marker) ; transmission electron microscopy and nanoparticle tracking analysis showed no significant differences in the morphology or size of the exosomes between the two groups. Compared with the blank control group, the exosome-treated group and CA exosome-treated group both showed obvious inhibition of the yeast-to-mycelial phase transition of CA, with a noticeable reduction in the length of the hyphae under the inverted microscope. ELISA revealed that the intracellular cAMP content in CA significantly decreased in the exosome-treated group and CA exosome-treated group (16.70 ± 0.84 pmol/ml, 16.82 ± 0.87 pmol/ml, respectively) compared with the blank control group (21.82 ± 1.08 pmol/ml; t = 6.45, 6.23, respectively, both P = 0.003). RT-qPCR revealed that the expression of the cAMP-related genes, RAS1 and CDC35, was down-regulated in the exosome-treated group and CA exosome-treated group compared with the blank control group (all P < 0.01), and the RAS1 mRNA expression was significantly lower in the CA exosome-treated group than in the exosome-treated group ( t = 7.43, P = 0.002) . Conclusion:Both M0 macrophage-derived exosomes and CA-infected M0 macrophage-derived exosomes could effectively inhibit the mycelial growth of CA, and the latter one exhibited a stronger inhibitory effect, possibly by down-regulating cAMP in the cAMP/protein kinase A pathway.

Background: Diabetes mellitus (DM) is a chronic metabolic disease that poses serious threats to human physical and mental health worldwide. The PDZ domain-containing 8 (PDZD8) protein mediates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) formation in mammals. We explored the role of PDZD8 in DM and investigated its potential mechanism of action. Methods: High-fat diet (HFD)- and streptozotocin-induced mouse DM and palmitic acid (PA)-induced insulin 1 (INS-1) cell models were constructed. PDZD8 expression was detected using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. MAM formation, interactions between voltage-dependent anion-selective channel 1 (VDAC1) and inositol 1,4,5-triphosphate receptor type 1 (IP3R1), pancreatic β-cell apoptosis and proliferation were detected using transmission electron microscopy (TEM), proximity ligation assay (PLA), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunofluorescence staining, and Western blotting. The mitochondrial membrane potential, cell apoptosis, cytotoxicity, and subcellular Ca2+ localization in INS-1 cells were detected using a JC-1 probe, flow cytometry, and an lactate dehydrogenase kit. Results: PDZD8 expression was up-regulated in the islets of HFD mice and PA-treated pancreatic β-cells. PDZD8 knockdown markedly shortened MAM perimeter, suppressed the expression of MAM-related proteins IP3R1, glucose-regulated protein 75 (GRP75), and VDAC1, inhibited the interaction between VDAC1 and IP3R1, alleviated mitochondrial dysfunction and ER stress, reduced the expression of ER stress-related proteins, and decreased apoptosis while increased proliferation of pancreatic β-cells. Additionally, PDZD8 knockdown alleviated Ca2+ flow into the mitochondria and decreased cyclophilin D (Cypd) expression. Cypd overexpression alleviated the promoting effect of PDZD8 knockdown on the apoptosis of β-cells. Conclusion PDZD8 knockdown inhibited pancreatic β-cell death in DM by alleviated ER-mitochondria contact and the flow of Ca2+ into the mitochondria.