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 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 investigate the clinical correlations between mechanical power (MP) and lung ultrasound score (LUS), and analyze their evaluation value of prognosis in patients with acute respiratory distress syndrome (ARDS). Methods Patients with moderate to severe ARDS, who underwent invasive mechanical ventilation admitted to intensive care unit (ICU) of the Lianyungang Affiliated Hospital of Xuzhou Medical University from January 2017 to March 2019 were enrolled. The MP and LUS were recorded 0, 24, 48 and 72 hours after ICU admission. The patients were divided into death group and survival group according to the 28-day prognosis. The trends of MP and LUS in the two groups and their differences between groups were analyzed. Then the MP and LUS were analyzed by bivariate correlation analysis, and their correlations with acute physiology and chronic health evaluationⅡ (APACHEⅡ), sequential organ failure assessment (SOFA), oxygenation index (PaO2/FiO2), and blood lactate (Lac) were also analyzed. The predictive value of MP and LUS 0 hour and 72 hours in ICU for 28-day mortality in patients with moderate to severe ARDS was analyzed by receiver operating characteristic (ROC) curve. Results At the end, 83 patients were enrolled, with 32 died and 51 survived in 28-day. The Lac level, APACHEⅡ and SOFA in the death group were significantly higher than those in the survival group, while PaO2/FiO2 was significantly lower than the survival group, and the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the MP and LUS of the survival group showed a significant decrease trend, while the death group showed a significant upward trend. The MP and LUS of the death group 0, 24, 48, 72 hours after ICU admission were significantly higher than those of the survival group [MP (J/min): 20.97±3.34 vs. 17.20±4.71, 21.56±3.48 vs. 16.87±3.85, 22.72±2.97 vs. 16.13±3.52, 25.81±3.46 vs. 15.24±3.78; LUS: 19.17±3.31 vs. 16.27±4.28, 20.28±3.65 vs. 15.27±3.23, 21.53±4.32 vs. 13.63±3.71, 23.94±3.82 vs. 12.53±2.94, all P < 0.05]. There was a significant positive correlation between MP and LUS 0, 24, 48, 72 hours after ICU admission (r value was 0.547, 0.577, 0.754, and 0.783, respectively, all P < 0.01). The MP and LUS at 0 hour of ICU admission were significantly positively correlated with SOFA and PaO2/FiO2 (r value was 0.421, 0.450, and 0.409, 0.536, respectively, all P < 0.01), but no correlation with Lac and APACHEⅡ was found. The ROC curve analysis showed that the MP and LUS at 0 hour and 72 hours had predictive value for the 28-day mortality [the area under the ROC curve (AUC) of MP was 0.836, 0.867; and the AUC of LUS was 0.820, 0.891, all P < 0.01]. Conclusions There was a significant correlation between MP and LUS in patients with moderate to severe ARDS. The MP and LUS could be used early to evaluate the 28-day prognosis of patients with moderate to severe ARDS.

objective:To observe the effect of high-flow nasal cannula (HFNC) oxygen therapy on patients with acute respiratory failure after gastrointestinal operation under general anesthesia and its efficacy on prognosis.Methods:Totally 107 patients with acute respiratory failure after gastrointestinal operation under general anesthesia in ICU of our hospital were selected from January 2017 to June 2019. Patients were randomly divided into the HFNC group ( n=57) and non-invasive ventilation (NIV) group ( n=50). The changes of pH, PaO 2, PaCO 2, PaO 2/FiO 2, SpO 2, heart rate (HR), respiration rate (RR), and intra-abdominal pressure (IAP) before and after oxygen treatment were compared. The differences of comfort level, duration of oxygen treatment, re-intubation rate, 48-h pulmonary infection rate, incidence of anastomotic fistula, length of stay in ICU, length of hospital stay, hospitalization cost, and 28-day mortality were compared between the two groups. The t test of two independent samples was used for the comparison of normal measurement data. Non-normal data were expressed by median (quartile), fractional count data by case number (percentage), and comparison between the two groups by Chi-square test. Results:PaO 2, PaCO 2, PaO 2/FiO 2 and SpO 2 were not significantly different after 2-h oxygen therapy. PH of the HFNC group was lower than that of the NIV group (7.39 ± 0.04 vs. 7.42 ± 0.03), PaO 2, PaCO 2, PaO 2/FiO 2 and SpO 2 were higher than that of the NIV group [ (89.22 ± 8.70) vs. (84.99± 9.76) mmHg, (41.3 ± 3.43) vs. (39.34 ± 4.21) mmHg, (250.07 ± 18.34) vs. (237.89±19.38) mmHg, (96.14 ± 2.19) vs. (94.78 ± 2.76)%, P <0.05]; pH, PaO 2, PaCO 2, PaO 2 /FiO 2 and SpO 2 were significantly higher in the HFNC group than those in the NIV group [ (7.39 ± 0.04) vs. (7.36 ± 0.04) ; (97.2 ± 12.45) vs. (93.82 ± 12.54) mmHg; (40.84 ± 5.22) vs. (45.10 ± 6.40) mmHg; (277.16 ± 13.98) vs. (248.86 ± 12.81) mmHg, (98.14 ± 1.64)% vs. (95.48 ± 2.71) %] after 12 h oxygen treatment. The HR, RR and IAP of the HFNC group were lower than those of the NIV group, and the differences were statistically significant ( P <0.05). The duration of oxygen therapy in the HFNC group was shorter than that in the NIV group [(32.01 ± 7.57) vs. (40.88 ± 8.89) h], the reintubation rate was lower than that in the NIV group (1.75% vs. 12%), the pulmonary infection rate within 48 h oxygen therapy was lower than that in the NIV group (8.78% vs.30%), and the length of stay in ICU was shorter than that in the NIV group [(5.61 ± 1.73) vs. (7.60 ± 2.31) d], and the hospitalization cost was lower than that in the NIV group ( t = 4.822, P <0. 05). Conclusions:HFNC can improve the oxygenation index of patients with hypoxemia after gastrointestinal operation under general anesthesia, reduce oxygen treatment time, reduced reintubation rate, reduce pulmonary infection rate within 48 h, and improve the prognosis.

Liver fibrosis/cirrhosis is the outcome of the progression of chronic hepatitis B and is associated with liver events and long-term prognosis. Effective antiviral therapy can delay or even reverse disease progression. Therefore, assessment of liver fibrosis degree before and during treatment is of great importance in initiating antiviral therapy, developing therapeutic regimens, and monitoring antiviral effects and complications. The semi-quantitative histological scoring system is widely acknowledged in the assessment of liver fibrosis degree and is an important basis for the initiation of antiviral therapy for hepatitis B, as well as a method commonly used for efficacy surveillance. Morphological and structural quantitative methods provide objective histological assessment of liver fibrosis and may cover the shortage of conventional semi-quantitative scoring system. Non-invasive methods for the assessment of liver fibrosis may reduce but not completely substitute liver histological examinations; a consensus has not been reached on their cut-off values to make decisions to initiate antiviral therapy, but such non-invasive methods can provide rich information on therapeutic effect and long-term prognosis.

Objective:To evaluate the value of lung ultrasound score (LUS) on predicting weaning outcome in patients with intro-abdominal infection (IAI) undergoing mechanical ventilation.Methods:Patients with IAI undergoing mechanical ventilation admitted to Research Institute of General Surgery of East War Zone Hospital and intensive care unit (ICU) of the First People's Hospital of Lianyungang from January to December in 2018 were included. The patients who satisfied weaning criteria were enrolled in the weaning process, which included spontaneous breathing trial (SBT) and extubation. They were divided into SBT success group and SBT failure group according to whether passed 120-minute SBT or not. LUS scores before and after SBT were compared between the two groups. The patients in the SBT success group were extubated, and they were divided into successful extubation group and failed extubation group for sub-group analysis according to whether re-intubation was needed in 48 hours after extubation. LUS score before extubation (at the end of SBT) and 48 hours after extubation (48 hours after extubation in the successful extubation group or before re-intubation in the failed extubation group) were compared. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of LUS score before SBT for SBT failure and LUS score before extubation for the failure.Results:A total of 76 patients with IAI undergoing mechanical ventilation were included. Twenty-three patients had duration of mechanical ventilation less than 48 hours, severe chronic obstructive pulmonary disease (COPD), tracheotomy or automatic discharge were excluded, and 53 patients were enrolled. SBT was failed in 9 patients, and successfully performed in 44 patients, of whom 23 patients with successful extubation, and 21 with failed extubation. The LUS scores before and after SBT in the SBT failure group were significantly higher than those in the SBT success group (before SBT: 13.22±1.99 vs. 10.79±1.64, t = -3.911, P = 0.000; after SBT: 19.00±1.12 vs. 13.41±1.86, t = -8.665, P = 0.000). ROC curve analysis showed that the area under ROC curve (AUC) of LUS score before SBT for predicting SBT failure was 0.82 [95% confidence interval (95% CI) was 0.67-0.98, P = 0.002]. When the optimum cut-off value was 12.5, the sensitivity was 66.7%, and the specificity was 84.1%. Sub-group analysis showed that the LUS scores before and after extubation in the failed extubation group were significantly higher than those in the successful extubation group (before extubation: 14.19±1.60 vs. 12.69±1.81, t = -2.881, P = 0.006; after extubation: 16.42±1.59 vs. 12.78±1.54, t = -7.710, P = 0.000). ROC curve analysis showed that the AUC of LUS score before extubation for predicting the failure was 0.81 (95% CI was 0.69-0.92, P = 0.000). When the optimum cut-off value was 13.5, the sensitivity was 80.0%, and the specificity was 65.2%. Conclusion:LUS score can effectively predict SBT outcome, risk of re-intubation after extubation in patients with IAI undergoing mechanical ventilation.

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.

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.