To investigate the protective effect and mechanism of Chimonanthus nitens Oliv. essential oil (CEO) on lipopolysaccharide (LPS)-induced inflammatory injury in intestinal epithelioid cell line No.6 (IEC-6) cells.
Methods
IEC-6 cells were stimulated with LPS to establish an inflammatory injury model, and CEO treatment was applied as an intervention. The cell counting kit-8 (CCK-8) assay was used to evaluate cell viability and determine the appropriate concentration for model induction. IEC-6 cells were divided into four groups: the control, CEO, LPS, and CEO + LPS groups. The CEO group and CEO + LPS group were pre-incubated with 20 mg / L CEO for 24 h, while the LPS group and CEO + LPS group were treated with 10 mg / L LPS to induce inflammatory injury. Interleukin-1 beta (IL-1β) secretion levels in the IEC-6 cell supernatants were measured using enzyme linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) generation was assessed using flow cytometry. The expression levels of P65, phosphorylated P65, Cleaved caspase-1, and vesicle-associated membrane protein-associated protein B (VAPB) in IEC-6 cells were determined by western-blotting. Mitochondrial membrane potential changes, mitochondrial calcium levels, mitochondria-associated endoplasmic reticulum membranes (MAMs) formation, and co-localization of NOD-like receptor protein 3 (NLRP3) with MAMs were examined using confocal microscopy.
Results
Significant differences were observed among the four groups in IL-1β secretion, P65 phosphorylation, Cleaved caspase-1 expression, ROS levels, mitochondrial membrane potential, mitochondrial calcium levels, and VAPB protein expression (F = 15.860, 22.260, 11.340, 65.220, 32.210, 15.800, 7.210; all P < 0.05). Compared with the control group, the IL-1β secretion, ROS production, P65 phosphorylation, Cleaved caspase-1 expression, mitochondrial calcium accumulation, and VAPB protein expression were significantly increased, while the mitochondrial membrane potential was decreased in the LPS group (all P < 0.05). Compared with the LPS group, the CEO + LPS group exhibited a significant increase in mitochondrial membrane potential, along with a reduction in IL-1β secretion, ROS production, P65 phosphorylation, Cleaved caspase-1 expression, mitochondrial calcium accumulation, and VAPB protein expression (all P < 0.05). Confocal microscopy showed that the formation of MAMs was less in the control group and CEO group, and the co-localization of NLRP3 with MAMs was also less. In the LPS group, the formation of MAMs increased, and the co-localization of NLRP3 with MAMs also increased. However, in the CEO + LPS group, the formation of MAMs and their co-localization with NLRP3 were improved.
Conclusions
CEO exerts a protective effect against LPS-induced inflammatory injury in IEC-6 cells. The underlying mechanism may involve the inhibition of nuclear factor kappa-B pathway activation and the regulation of VAPB protein expression, thereby influencing MAMs formation and function to mitigate mitochondrial damage.
To develop a prediction model for the prolonged ICU stay in patients with drug poisoning based on machine learning algorithms.
Methods
Drug poisoning patients included in the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) and Electronic Intensive Care Unit-Collaborative Research Database (eICU-CRD) were divided into a non-prolonged group (≤ 48 hours) and a prolonged group (> 48 hours) according to the length of ICU stay. A total of 1 342 patients in MIMIC-Ⅳ were divided into a training dataset (939 cases) and a test dataset (403 cases) at a ratio of 7 ∶ 3, with eICU-CRD serving as an external test dataset (2 144 cases). In the training dataset, variables were jointly screened through single-factor analysis and least absolute shrinkage and selection operator (LASSO) regression. Six machine learning algorithms (logistic regression, extreme gradient boosting, light gradient boosting machine, random forest, decision tree, and support vector machine) were used for modeling. Meanwhile, the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow (H-L) test, Brier score, and decision curve analysis (DCA) were used to evaluate the model performance in both internal and external test datasets.
Results
Seven critical predictors were screened out in the training dataset: cerebrovascular disease, liver disease, aspiration pneumonia, sepsis, respiratory rate, sequential organ failure assessment (SOFA) score, and mechanical ventilation. The logistic regression model performed best in the training dataset [area under the curve (AUC) = 0.767, 95% confidence interval (CI) (0.667, 0.868), P < 0.001]. Its AUC was 0.762 [95%CI (0.712, 0.811), P < 0.001] in the internal test dataset, and 0.732 [95%CI (0.708, 0.756), P < 0.001] in the external test dataset. Moreover, the logistic regression model showed good calibration and net returns in both internal and external test datasets.
Conclusions
The logistic regression model constructed in this study consists of seven predictive factors, including cerebrovascular disease, liver disease, aspiration pneumonia, sepsis, respiratory rate, SOFA score, and mechanical ventilation. It can effectively predict the risk of prolonged ICU stay in drug poisoning patients, which is helpful for early clinical identification and intervention.
To explore the effectiveness of healthcare failure mode and effect analysis (HFMEA) in the safety management of clinical trial drug infusion.
Methods
Under the guidance of HFMEA theory, a risk assessment was conducted on the clinical trial drug infusion management process. Potential failure modes were analyzed, and the causes and effects of failure were explored. Based on risk factors, improvement measures were developed and implemented, and then the improvement effectiveness was evaluated, including the risk priority number (RPN), standardization rates of drug infusion, infusion bottle stickers, medical consumables, data collection and document recording, and satisfaction of nurses and doctors.
Results
Through decision tree analysis, 28 potential failure causes were identified as key improvement targets. After implementing the HFMEA model, the total RPN score decreased from 247 to 93, with a decrease of 62.3%. Meanwhile, there were no adverse nursing events related to clinical trials. The standardization rates of drug infusion [95.0% (95 / 100) vs. 86.0% (86 / 100), χ2 = 4.711, P = 0.030], infusion bottle stickers [100.0% (100 / 100) vs. 75.0% (75 / 100), χ2 = 28.571, P < 0.001], medical consumables [96.0% (288 / 300) vs. 77.7% (233 / 300), χ2 = 44.097, P < 0.001], data collection [93.0% (93 / 100) vs. 82.0% (82 / 100), χ2 = 5.531, P = 0.019], and document recording [90.0% (90 / 100) vs. 76.0% (76 / 100), χ2 = 6.945, P = 0.008] after implementation all significantly improved compared with those before implementation. Besides, the satisfaction scores of nurses and doctors increased from (4.2 ± 2.0) and (6.5 ± 2.4) before implementation to (8.2 ± 1.5) and (8.9 ± 1.2) after implementation respectively (t = 4.309, P = 0.040; t = 55.910, P < 0.001).
Conclusion
The prospective application of HFMEA can effectively improve the safety management level of clinical trial drug infusion by shifting passive post treatment to proactive prevention.
To explore the characteristics of traditional Chinese medicine constitutions in hospitalized elderly patients and their influence on the risk of common geriatric syndromes.
Methods
A total of 524 elderly patients admitted to the Department of Geriatrics of the First Affiliated Hospital, Zhejiang University School of Medicine from November 2023 to October 2024 were selected as the study subjects. According to their traditional Chinese medicine constitutions, patients were divided into the yang-deficient constitution (69 cases), qi-deficient constitution (244 cases), yin-deficient constitution (154 cases), gentleness constitution (15 cases), and other constitution (42 cases). The gender, age, educational level, smoking and drinking habits, and occurrence of common geriatric syndromes (frailty, sarcopenia, disability, and sleep disorders) of these elderly patients with different traditional Chinese medicine constitutions were compared. The different tongue colors of patients with common geriatric syndromes were detected and compared. Univariate and multivariate logistic regression analyses were used to investigate the influence of different traditional Chinese medicine constitutions on the risk of common geriatric syndromes.
Results
The proportion of qi-deficient constitution was the highest [46.56% (244 / 524)] among hospitalized elderly patients, followed by the yin-deficient constitution [29.39% (154 / 524)] and yang-deficient constitution [13.17% (69 / 524)]. The gender ( χ2 = 13.795, P = 0.008), age (F = 4.806, P < 0.001), frailty ( χ2 = 10.640, P = 0.031), sarcopenia ( χ2 = 11.530, P = 0.021), disability ( χ2 = 13.083, P = 0.011), and sleep disorders ( χ2 = 9.870, P = 0.043) among elderly patients with different traditional Chinese medicine constitutions all showed significant differences. Moreover, compared with the yin-deficient constitution, the proportions of males, sarcopenia, and disability were higher in patients with yang-deficient constitution (all P < 0.005), with an older age (P < 0.05), and the proportion of disability was also higher in patients with qi-deficient constitution (P < 0.005). Compared with the gentleness constitution, the proportion of sleep disorders was higher in patients with yang-deficient constitution (P < 0.005). There were statistically significant differences in the proportions of different tongue colors among elderly patients with sarcopenia ( χ2 = 11.318, P = 0.010) and disability ( χ2 = 19.561, P < 0.001), and the proportion of red tongue in elderly patients with sarcopenia and disability was higher than that of pale red tongue (both P < 0.008). Univariate and multivariate logistic regression analyses revealed that compared with the yang-deficient constitution, the risk of sarcopenia in elderly patients with gentleness constitution was significantly reduced [odds ratio (OR) = 0.260, 95% confidence interval (CI) (0.071, 0.958), P = 0.043], and the risk of sleep disorders in elderly patients with qi-deficient constitution [OR = 0.418, 95%CI (0.187, 0.936), P = 0.034] and gentleness constitution [OR = 0.147, 95%CI (0.041, 0.521), P = 0.003] was also remarkedly decreased.
Conclusions
Hospitalized elderly patients predominantly exhibit qi-deficient, yang-deficient, and yin-deficient constitutions. The proportion of geriatric syndromes is high in patients with biased constitutions (especially the yang-deficient constitution), and the risk of sarcopenia and sleep disorders is relatively high in patients with yang-deficient constitution.