Role of Charlson comorbidity index in predicting the ICU admission in patients with thoracic aortic aneurysm undergoing surgery.

OBJECTIVES: This study aimed to explore the value of the Charlson comorbidity index (CCI) in predicting ICU admission in patients with aortic aneurysm (AA). METHODS: The clinical data of patients were obtained from the Medical Information Mart for Intensive Care-IV database. The association between CCI and ICU admission was explored by restricted cubic spline (RCS), threshold effect analysis, generalized linear model, logistic regression, interaction, and mediation analyses. Its clinical value was evaluated by decision curve analysis (DCA), receiver operating characteristic curve (ROC), DeLong's test, and net reclassification index (NRI) analyses. RESULTS: The ICU admission was significantly associated with the thoracic AA (TAA), unruptured status, and surgery status. Therefore, 288 candidate patients with unruptured TAA who received surgery were enrolled in the further analysis. We found that CCI was independently associated with the ICU admission of candidates (P = 0.005). Further, their nonlinear relationship was observed (adjusted P = 0.008), and a significant turning point of 6 was identified. The CCI had a favorable performance in predicting ICU admission (area under curve = 0.728) and achieved a better clinical net benefit. New models based on CCI significantly improved the accuracy of prediction. Besides the importance of CCI in ICU admission, CCI also exerted important interaction effect (rather than mediating effects) on the association of other variables (such as age and blood variables) with ICU admission requirements (all P < 0.05). CONCLUSIONS: The CCI is an important predictor of ICU admission after surgery in patients with unruptured TAA.

Bufei Yishen Formula Inhibits the Cell Senescence in COPD by Up-Regulating the ZNF263 and Klotho Expression.

Background: Bufei Yishen formula (BYF) is an effective prescription for the clinical treatment of chronic obstructive pulmonary disease (COPD). However, the molecular mechanism by which it exerts its pharmacological effects remains to be explored. Methods: The human bronchial cell line BEAS-2B was treated with cigarette smoke extract (CSE). Cellular senescence markers were detected by Western blot and ELISA. Potential transcription factor of klotho was predicted using JASPAR and USCS databases. Results: CSE induced cellular senescence with intracellular accumulation of cellular senescence biomarkers (p16, p21 and p27) and increased secretion of senescence-related secretory phenotypic (SASP) factors (IL-6, IL-8, and CCL3). In contrast, BYF treatment inhibited CSE-induced cellular senescence. CSE suppressed the transcription, expression and secretion of klotho, whereas BYF treatment rescued its transcription, expression and secretion. CSE downregulated the protein level of ZNF263, whereas BYF treatment rescued the expression of ZNF263. Furthermore, ZNF263-overexpressing BEAS-2B cells could inhibit CSE-induced cellular senescence and SASP factor secretion by upregulating the expression of klotho. Conclusion: This study revealed a novel pharmacological mechanism by which BYF alleviates clinical symptoms of COPD patients, and regulating ZNF263 and klotho expression may be beneficial to the treatment and prevention of COPD.

Therapeutic effects of human umbilical cord mesenchymal stem cell on sepsis-associated encephalopathy in mice by regulating PI3K/AKT pathway.

Sepsis-associated encephalopathy is a common brain diseases, presenting severe diffuse brain dysfunction. The umbilical cord mesenchymal stem cells have been reported to have protective role for treating diseases, while its role in sepsis-associated encephalopathy remained elusive. This brief report investigated the therapeutic effect of umbilical cord mesenchymal stem cells on sepsis-associated encephalopathy in mice model and uncovering the underlying mechanism. The sepsis-associated encephalopathy mice were injected with 3 mg/kg lipopolysaccharide. An enzyme-linked immunosorbent assay was carried out to determine the production of inflammatory cytokines. Morris water maze test was used to evaluate mice's neurological dysfunction. Cell apoptosis and tissue injury of the cerebral cortex were assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and HE staining. Evans Blue leakage detection was used to examine the blood-brain barrier integrity. The protein levels were determined using Western blot. Results showed that the productions of inflammatory cytokines including interleukin 6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), and high mobility group box protein 1 (HMGB1) and activated NF-κB were increased in sepsis-associated encephalopathy mice, which were decreased by umbilical cord mesenchymal stem cells treatment. Besides, umbilical cord mesenchymal stem cells inhibited lipopolysaccharide-induced cell apoptosis and neuron injury of the cerebral cortex in sepsis-associated encephalopathy mice. Moreover, cognitive dysfunction was observed in sepsis-associated encephalopathy mice, which was alleviated by umbilical cord mesenchymal stem cells. Furthermore, umbilical cord mesenchymal stem cells activated PI3K/AKT signaling pathway. In conclusion, umbilical cord mesenchymal stem cells alleviated inflammation, cell apoptosis and neuron injury of the cerebral cortex, and cognitive dysfunction in sepsis-associated encephalopathy animal model in a PI3K/AKT dependent pathway, making them to be a promising therapeutic strategy for treating sepsis-associated encephalopathy.

Mechanism of Action of Bu-Fei-Yi-Shen Formula in Treating Chronic Obstructive Pulmonary Disease Based on Network Pharmacology Analysis and Molecular Docking Validation.

OBJECTIVE: To explore the mechanism of action of Bu-Fei-Yi-Shen formula (BFYSF) in treating chronic obstructive pulmonary disease (COPD) based on network pharmacology analysis and molecular docking validation. METHODS: First of all, the pharmacologically active ingredients and corresponding targets in BFYSF were mined by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, the analysis platform, and literature review. Subsequently, the COPD-related targets (including the pathogenic targets and known therapeutic targets) were identified through the TTD, CTD, DisGeNet, and GeneCards databases. Thereafter, Cytoscape was employed to construct the candidate component-target network of BFYSF in the treatment of COPD. Moreover, the cytoHubba plug-in was utilized to calculate the topological parameters of nodes in the network; then, the core components and core targets of BFYSF in the treatment of COPD were extracted according to the degree value (greater than or equal to the median degree values for all nodes in the network) to construct the core network. Further, the Autodock vina software was adopted for molecular docking study on the core active ingredients and core targets, so as to verify the above-mentioned network pharmacology analysis results. Finally, the Omicshare database was applied in enrichment analysis of the biological functions of core targets and the involved signaling pathways. RESULTS: In the core component-target network of BFYSF in treating COPD, there were 30 active ingredients and 37 core targets. Enrichment analysis suggested that these 37 core targets were mainly involved in the regulation of biological functions, such as response to biological and chemical stimuli, multiple cellular life processes, immunity, and metabolism. Besides, multiple pathways, including IL-17, Toll-like receptor (TLR), TNF, and HIF-1, played certain roles in the effect of BFYSF on treating COPD. CONCLUSION: BFYSF can treat COPD through the multicomponent, multitarget, and multipathway synergistic network, which provides basic data for intensively exploring the mechanism of action of BFYSF in treating COPD.

Intravenous thiamine for septic shock: A meta-analysis of randomized controlled trials.

INTRODUCTION: The efficacy of intravenous thiamine to treat septic shock remains controversial. We conduct a systematic review and meta-analysis to explore the impact of intravenous thiamine on treatment efficacy of septic shock. METHODS: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2020 and included randomized controlled trials (RCTs) assessing the effect of intravenous thiamine on septic shock. This meta-analysis was performed using the random-effect model. RESULTS: Four RCTs were included in the meta-analysis. Overall, compared with control group in patients with septic shock, intravenous thiamine revealed no substantial impact on mortality (odd ratio [OR] = 0.87; 95% confidence interval [CI) = 0.62 to 1.21; P = 0.40), lactate change (standard mean difference [SMD] = 0.04; 95% CI = -0.28 to 0.35; P = 0.82), Sequential Organ Failure Assessment (SOFA) change (SMD = 0.02; 95% CI = -0.18 to 0.21; P = 0.87), intensive care unit (ICU) stay (SMD = -0.02; 95% CI = -0.33 to 0.30; P = 0.90) or renal replacement therapy (OR = 0.47; 95% CI = 0.07 to 3.15; P = 0.43). CONCLUSIONS: Intravenous thiamine showed no benefit over placebo in treating patients with septic shock.

Differential analysis of clinical efficacy on patients with serious infection in ICU by different meropenem regimens.

To investigate the difference in clinical efficacy and safety of different meropenem regimens on patients with serious infection in ICU. Then, 228 patients with serious infection in ICU were divided by random into control group (intermittent administration in 1000mg/30min single dose) and research group (continuous administration in 200mg/10min +800mg/180min), respectively. The blood concentration of meropenem were recorded in two groups at different time points, and difference in treatment effectiveness, iconographic effectiveness, bacterial eradication rate, 28-day survival rate and many other clinical scoring indices (SOFA, APACHEII, CPIS, and SIRS) were compared between two groups. There were 212 patients completing the whole research, including 104 patients in research group and 108 patients in control group. The difference in treatment effectiveness (77.8% vs 53.7%), iconographic effectiveness (51.0% vs 18.5%), and 28-day survival rate (86.5% vs 64.8%) between two groups performed statistical significance (P<0.05). However, the difference in bacterial eradication rate (48.0% vs 46.3%) performed no statistical significance. Eight hours later, the difference in average blood concentration between two groups (9.61±3.63µg/ml vs 1.5±0.51µg/ml) showed statistical significance. Moreover, the difference in clinical scoring indices except APACHE II score between two groups performed statistical significance. It was helpful to maintain the blood concentration of meropenem by extending the transfusion time. Therefore, it could increase the clinical cure rate and 28-day survival of patients with serious infection in ICU, improve clinical indices, and reduce the usage amount of antibiotics.