BACKGROUND:It has been shown that neural stem cells can differentiate into neurons,astrocytes,and oligodendrocytes.Mesenchymal stem cells-derived extracellular vesicles have also been shown to cross the blood-brain barrier to reach sites of central nervous injury and promote neural repair.However,it is not clear whether neuron-derived extracellular vesicles promote the differentiation of neural stem cells in a direction that is beneficial for neurogenesis. OBJECTIVE:To investigate whether neuron-derived extracellular vesicles facilitate neural stem cell differentiation towards neurogenesis. METHODS:Neurons and neural stem cells were extracted from neonatal SD rat cerebral cortex by trypsin digestion.Cell supernatants of neurons were collected.Neuron-derived extracellular vesicles were extracted.Neural stem cells cultured for 10 days were co-cultured with neuron-derived extracellular vesicles or PBS for 7 days.Immunoblotting,immunofluorescence,and RT-qPCR were used to detect proteins specifically expressed by neurons,neural stem cells,oligodendrocytes,and astrocytes. RESULTS AND CONCLUSION:The neural stem cells co-cultured with neuron-derived extracellular vesicles showed high expression of neuron-specific proteins and oligodendrocyte-specific proteins including β3-tubulin,neurofilament 200 and myelin basic protein,and low expression of astrocyte-specific protein glial fibrillary acidic protein.These results suggest that neuron-derived extracellular vesicles can promote the differentiation of neural stem cells into neurons and oligodendrocytes and prevent the differentiation of neural stem cells into astrocytes.

Objective:To investigate the role and mechanism of molecular hydrogen in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:Balb/c male mice were randomly(random number) divided into control group, control+H 2, LPS and LPS+H 2 group with 6 mice in each group. The levels of malondialdehyde (MDA) and Fe 2+ in lung tissue were detected by kits. The lung tissue morphology was observed. The infiltration levels of F4/80 positive macrophages in lung tissue were detected by immunofluorescence staining. A549 cells were divided into control, control+H 2, erastin and erastin+H 2 group. The reactive oxygen species (ROS), malondialdehyde, (MDA), lactate dehydrogenase (GSH), number of cell death and lactate dehydrogenase (LDH) release in each group were detected by kits. Nrf2, GPX4, and HO-1mRNA were quantified by real-time PCR, the protein expression level of Nrf2 was detected by western blot, and the nuclear translocation level of Nrf2 was observed by immunofluorescence. The chi-square test was performed before the measurement data were counted. One-way analysis of variance was used to compare differences between multiple groups. Results:Compared with the control group, the histopathological damage was aggravated, and the levels of MDA, Fe 2+ significantly increased in the LPS group, and F4/80 positive immune cells infiltration significantly increased (all P<0.05). Compared with LPS group, the degree of lung injury in LPS+H 2 group significantly reduced (all P<0.05). In vitro experiments, compared with the control group, the ROS, MDA levels, number of cell death and LDH release significantly increased in erastin group (all P<0.05), while GSH, and GPX4 mRNA levels decreased (all P<0.05). HO-1mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Compared with erastin group, ROS, MDA levels, cell death number and LDH release decreased in earstin+H 2 group (all P<0.05). The levels of GSH, GPX4 mRNA, Nrf2 mRNA, HO-1 mRNA and Nrf2 nuclear translocation levels increased (all P<0.05). Conclusions:Molecular hydrogen attenuates LPS-induced ALI by promoting Nrf2 nuclear translocation to inhibit ferroptosis of alveolar epithelial cells.

Objective:To explore the predictive value of myocardial work echocardiography on short-term mortality of patients with sepsis and septic shock(SSS).Methods:Patients who hospitalized in the ICU department of the Affiliated Lianyungang Hospital of Xuzhou Medical University from September 2022 to December 2023 were selected through prospective research.These patients,who need use vasopressor drugs,appeared clinical symptoms of sepsis and occurred septic shock.A total of 33 adult patients were continuously enrolled.According to whether patients with SSS died or survived within 28 days,they were divided into a survival group(23 cases)and a non-survival group(10 cases).The changes of myocardial function,serum lactic acid level,white blood cell(WBC)count,c-reactive protein(CRP)and other indexes were compared and assessed between the two groups after admission,and the predictive value of these parameters on short-term mortality in patients with sepsis and septic shock was investigated.Results:On the 3rd day after admission of patients with sepsis and septic shock,the heart rate,serum lactic acid level,white blood cell(WBC)count,global wasted work(GWW),and high-sensitivity cardiac troponin Ⅰ(hs-cTnⅠ)of non-survival group significantly higher than those of survival group(Z=-2.668,-2.550,-2.338,-2.175,-2.998,P＜0.05),and the global work efficiency(GWE)of non-survival group significantly decreased(Z=-2.311,P＜0.05).On the 5th day after admission,the heart rate,serum lactic acid level,WBC count,c-reactive protein(CRP)level of non-survival group significantly increased(Z=-3.073,-2.494,-3.408,-2.999,P＜0.05),and the pH value and global work index(GWI)of that significantly decreased(Z=-1.997,-2.546,P＜0.05).Serum lactic acid on the 3rd day and global work index on the 5th day were respectively independent risk factors for 28-day mortality in SSS patients after admission(OR=5.120,0.997,P＜0.05).On the 5rd GwI and serum lactic acid on the 3rd have similar values in predicting 28-day mortality in SSS patients[area under curve(AUC)value of receiver operating characteristics(ROC)curve of them were respectively 0.784 and 0.801,P＞0.05].Conclusion:Myocardial work echocardiography is helpful to identify the high risk of short-term death of SSS patients.Serum lactic acid of the 3rd day and global work index of the 5th day after admission are respectively independent risk factors for 28-day death in SSS patients.

The systemic inflammatory response caused by various pathogenic factors is a key stage in the development of acute respiratory distress syndrome (ARDS). At present, suppression of the inflammatory response and symptomatic support are main methods for the treatment of ARDS. Alveolar epithelial autophagy has an important role in the regulation of the inflammatory response in ARDS. Autophagy is a normal immune mechanism in the body, and it is a metabolic process by which phagocytes degrade intracellular components with the help of lysosomes to maintain intracellular homeostasis. Current studies have shown that pathogenic factors both inside and outside the lung can cause alveolar epithelial cells to form an unfavorable internal environment of hypoxia, starvation, infection, and even apoptosis by triggering inflammatory responses, leading to autophagy dysfunction. Excessive autophagy activation can continue to aggravate inflammatory responses. Autophagy related proteins such as Beclin1, microtubule-associated protein 1 light chain 3 (LC3), mammalian target of rapamycin (mTOR), and p62 are common autophagic markers in current research, which play a crucial role in regulating the autophagic process and the development of lung injury. Therefore, the expression of cellular autophagy genes can be used as early markers and important mechanisms of lung injury in septic ARDS. The Hippo signaling pathway is derived from the protein kinase Hippo in Drosophila, and the Hippo and autophagy are two conserved pathways that are essential for the protection of homeostasis in vivo. The mutual regulation of Hippo signaling pathway and autophagy is currently a hot topic in the academic community. This paper reviews the relevant literature to explore whether the Hippo signaling pathway can regulate cellular autophagy to alleviate the inflammatory response in septic ARDS, so as to provide further research directions for the treatment of ARDS.

OBJECTIVE: To develop and validate a mechanical power (MP)-oriented nomogram prediction model of weaning failure in mechanically ventilated patients. METHODS: Patients who underwent invasive mechanical ventilation (IMV) for more than 24 hours and were weaned using a T-tube ventilation strategy were collected from the Medical Information Mart for Intensive Care-IV v1.0 (MIMIC-IV v1.0) database. Demographic information and comorbidities, respiratory mechanics parameters 4 hours before the first spontaneous breathing trial (SBT), laboratory parameters preceding the SBT, vital signs and blood gas analysis during SBT, length of intensive care unit (ICU) stay and IMV duration were collected and all eligible patients were enrolled into the model group. Lasso method was used to screen the risk factors affecting weaning outcomes, which were included in the multivariate Logistic regression analysis. R software was used to construct the nomogram prediction model and build the dynamic web page nomogram. The discrimination and accuracy of the nomogram were assessed by receiver operator characteristic curve (ROC curve) and calibration curves, and the clinical validity was assessed by decision curve analysis (DCA). The data of patients undergoing mechanical ventilation hospitalized in ICU of the First People's Hospital of Lianyungang City and the Second People's Hospital of Lianyungang City from November 2021 to October 2022 were prospectively collected to externally validate the model. RESULTS: A total of 3 695 mechanically ventilated patients were included in the model group, and the weaning failure rate was 38.5% (1 421/3 695). Lasso regression analysis finally screened out six variables, including positive end-expiratory pressure (PEEP), MP, dynamic lung compliance (Cdyn), inspired oxygen concentration (FiO₂), length of ICU stay and IMV duration, with coefficients of 0.144, 0.047, -0.032, 0.027, 0.090 and 0.098, respectively. Logistic regression analysis showed that the six variables were all independent risk factors for predicting weaning failure risk [odds ratio (OR) and 95% confidence interval (95%CI) were 1.155 (1.111-1.200), 1.048 (1.031-1.066), 0.968 (0.963-0.974), 1.028 (1.017-1.038), 1.095 (1.076-1.113), and 1.103 (1.070-1.137), all P < 0.01]. The MP-oriented nomogram prediction model of weaning failure in mechanically ventilated patients showed accurate discrimination both in the model group and external validation group, with area under the ROC curve (AUC) and 95%CI of 0.832 (0.819-0.845) and 0.879 (0.833-0.925), respectively. Furthermore, its predictive accuracy was significantly higher than that of individual indicators such as MP, Cdyn, and PEEP. Calibration curves showed good correlation between predicted and observed outcomes. DCA indicated that the nomogram model had high net benefits, and was clinically beneficial. CONCLUSIONS The MP-oriented nomogram prediction model of weaning failure accurately predicts the risk of weaning failure in mechanical ventilation patients and provides valuable information for clinicians making decisions on weaning.
Humans ; Respiration, Artificial/methods* ; Ventilator Weaning/methods* ; Nomograms ; Lung ; Risk Factors

Objective:To explore the relevance of a new comprehensive respiratory mechanics parameter, elastic power, to the 28-day prognosis of ARDS patients.Methods:Patients with ARDS hospitalized for at least 48 h with invasive mechanical ventilation in five intensive care units in three local hospitals in Lianyungang City from June 2018 to June 2022 were included in the study. Their baseline data and respiratory mechanics parameters were collected. Elastic power, mechanical power, driving pressure and lung compliance are calculated according to the corresponding formulae. The prognostic risk factors of ARDS patients were analysed using COX multi-factor regression, and the predictive value of EP/Cst on the 28-day prognosis of ARDS patients was evaluated based on ROC curve analysis and Kaplan-Meier survival curve.Results:There was no significantly difference in tidal volume and PEEP settings between the patients in the ARDS survivor and death groups ( P> 0.05). However, the differences in respiratory rate, plateau pressure, driving pressure, lung compliance, mechanical work, elastic work, EP/cst and MP/cst between the two groups were significantly different (all P< 0.01). Multifactorial COX regression analysis showed that EP/cst ( HR=1.211, 95% CI:1.091-1.323) and RR ( HR=1.209, 95% CI:1.046-1.339) were strongly associated with a more severe degree of illness and a worse prognosis in ARDS. And the cumulative survival rate at 28 d was significantly lower in the high Cst-EP group than in the low Cst-EP group (50.00% vs. 82.40%, P < 0.01). Conclusions:The new respiratory mechanics parameters EP and EP/Cst can assess the severity of ARDS with a good predictive effect on patient prognosis at 28 days.

Objective:To explore the diagnostic value of mechanical power (MP) in patients with moderate to severe acute respiratory distress syndrome (ARDS) based on the Medical Information Mart for Intensive Care-Ⅲv1.4 (MIMIC-Ⅲ v1.4).Methods:The information of ARDS patients undergoing invasive mechanical ventilation for no less than 48 hours who were hospitalized at Beth Israel Deaconess Medical Center in Boston, Massachusetts from June 2001 to October 2012 in the MIMIC-Ⅲ v1.4 were collected. The demographics of patients, disease severity scores, ARDS etiology, prognostic indicators, pre-ventilation arterial blood gas analysis and respiratory parameters within 48 hours of ventilation were extracted. According to the lowest oxygenation index (PaO 2/FiO 2) before ventilation, the patients were divided into mild to moderate ARDS group (> 150 mmHg, 1 mmHg≈0.133 kPa) and moderate to severe ARDS group (≤ 150 mmHg), and the differences in baseline characteristics between the two groups were compared. The independent predictors associated with the severity of ARDS were analyzed using Logistic regression. The receiver operator characteristic curve (ROC curve) was plotted. The area under ROC curve (AUC) was calculated to evaluate the diagnostic value of MP for moderate to severe ARDS. The Youden index was used to determine the diagnostic threshold of MP for moderate to severe ARDS. According to the cut-off value of MP based on Youden index, all ARDS patients were divided into high and low MP groups. Kaplan-Meier survival curve was used to analyze the 28-day survival status of patients. Results:A total of 403 ARDS patients were enrolled in the study, including 107 subjects with mild to moderate ARDS and 296 with moderate to severe ARDS. There were significant differences in age, sequential organ failure assessment (SOFA) score, the lowest PaO 2/FiO 2 before ventilation, the last PaO 2/FiO 2 before ventilation, 28-day mortality, the length of intensive care unit (ICU) stay, duration of mechanical ventilation, lung dynamic compliance (Cdyn) in the second 24 hours of ventilation and positive end-expiratory pressure (PEEP), plateau pressure (Pplat), driving pressure (ΔP), respiratory rate (RR), lung static compliance (Cst), MP, inspired fraction of oxygen (FiO 2) within 48 hours of ventilation between the two groups. After adjusting variables such as age, SOFA score, the last PaO 2/FiO 2 before ventilation, and related respiratory mechanics parameters, multivariate Logistic regression analysis showed that higher ΔP, PEEP and MP, and lower last PaO 2/FiO 2 before ventilation were independently associated with moderate to severe ARDS [odds ratio ( OR) and 95% confidence interval (95% CI) was 1.137 (1.032-1.252), 1.333 (1.139-1.561), 1.102 (1.030-1.179), and 0.996 (0.993-0.998), respectively, all P < 0.01]. The ROC curve analysis showed that the best cut-off value of MP for the diagnosis of moderate to severe ARDS was 18.1 J/min with sensitivity of 81.42% and specificity of 60.75%, and the AUC was 0.745 (95% CI was 0.690-0.799). According to the cut-off value of MP obtained by ROC curve, all ARDS patients were divided into high MP group (> 18.1 J/min) and low MP group (≤ 18.1 J/min). The Kaplan-Meier survival curve showed that the 28-day cumulative survival rate in the high MP group was significantly lower than that in the low MP group (73.8% vs. 85.1%; Log-Rank test: χ2 = 5.660, P = 0.017). Conclusion:MP is an independent predictor of the severity of ARDS, and it can be used to diagnose moderate to severe ARDS.

Objective:To explore the diagnosis process and treatment experience of severe coronavirus disease 2019 (COVID-19) patients with heparin resistance (HR).Methods:The medical team of the First People's Hospital of Lianyungang admitted 2 severe COVID-19 patients with HR in intensive care unit (ICU) during their support to the designated hospital for the treatment of COVID-19 patients in Lianyungang City in November 2021. The clinical features, laboratory examinations, imaging features, treatment and prognosis of the two patients were analyzed.Results:Both severe COVID-19 patients received mechanical ventilation, 1 patient was treated with extracorporeal membrane oxygenation (ECMO) support. Both patients were complicated with lower extremity deep venous thrombosis and HR phenomenon under routine dose anticoagulant therapy. The maximum daily dose of unfractionated heparin exceeded 35 000 U (up to 43 200 U), the 2 patients failed to meet the standard of anticoagulation treatment, and the course of disease was prolonged. After that, argatroban was given 0.4 μg·kg -1·min -1 combined with anticoagulant therapy, the activated partial thromboplastin time (APTT) of patients undergoing ECMO could be maintained at 55-60 seconds and the activated coagulation time (ACT) of them could be maintained at 180-200 seconds. After ECMO support or later sequential mechanical ventilation, both patients recovered and were discharged, and deep venous thrombosis was also effectively controlled. Conclusion:HR phenomenon often occurs during the treatment of severe COVID-19 patients, the anticoagulation regimen should be adjusted in time, and the anticoagulation effect combined with argatroban is clear.

Objective:To analyze the differentially expressed gene (DEG) in rats with sepsis-induced exogenous acute respiratory distress syndrome (ARDS) and explore the early diagnosis and protective mechanism of sepsis-induced ARDS at the transcriptome level.Methods:Twelve 6 to 8 weeks old male Sprague-Dawley (SD) rats were randomly divided into lipopolysaccharide (LPS) induced sepsis-induced ARDS model group (model group, intraperitoneal injection of LPS 15 mg/kg) and control group (intraperitoneal injection of the same volume of normal saline), with 6 rats in each group. RNA was extracted from the left lung tissue of the two groups, and the paired-end sequencing mode of the illumina Hiseq sequencing platform was used for high-throughput sequencing. The DESeq2 software was used to screen DEG with | log 2 (fold change, FC) | ≥ 3 and P < 0.001. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on DEG. STRING and CytoScape software were used to construct a protein-protein interaction (PPI) network and screen key genes. The peripheral blood mononuclear cell (PBMC) of 20 septic patients admitted to the emergency and critical care medical department of Lianyungang First People's Hospital from March to November 2021 and 20 age-matched healthy people in the same period were isolated and extracted, and the key genes were verified by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Results:A total of 286 DEG were screened, including 202 up-regulated genes and 84 down-regulated genes. GO enrichment analysis showed that DEG was mainly involved in biological processes such as neutrophil chemotaxis migration, antibacterial humoral response, host immune response, and humoral immune response. KEGG analysis showed that DEG mainly played a biological role through interleukin-17 (IL-17) signaling pathway, tumor necrosis factor (TNF) signaling pathway, and chemokine signaling pathway. In PPI analysis, a total of 262 node proteins were screened, and the interaction relationship was 852 edges. The first 15 key genes were IL-6, TNF, IL-10, IL-1β, chemokine ligand 1 (CXCL1), CXCL10, chemokine receptor 3 (CXCR3), CXCR2, CXCL9, chemokine ligand 7 (CCL7), CXCL11, CCL1, CXCL13, CCL12, and CCL22. Five representative key genes were performed on PBMC of blood samples from septic ARDS patients and healthy controls by RT-qPCR. The results showed that their expression was significantly higher than that in the healthy controls [IL-6 mRNA (2 -ΔΔCt): 2.803±1.081 vs. 0.951±0.359, TNF mRNA (2 -ΔΔCt): 2.376±0.799 vs. 1.150±0.504, CXCL10 mRNA (2 -ΔΔCt): 2.500±0.815 vs. 1.107±0.515, CXCR3 mRNA (2 -ΔΔCt): 1.655±0.628 vs. 0.720±0.388, CCL22 mRNA (2 -ΔΔCt): 1.804±0.878 vs. 1.010±0.850, all P < 0.05], and the trends were consistent with the RNA-Seq results. Conclusion:Biological processes such as chemotactic migration and degranulation of inflammatory cells, cytokine immune response, and signal pathways such as CXCL10/CXCR3 and IL-17 play important roles in the occurrence and development of sepsis-related exogenous ARDS, which would provide new ideas and targets for further study of lung injury mechanisms and clinical prevention and treatment.