BACKGROUND:Patients with Alzheimer's disease have severe brain energy disorders.In recent years,brain energy rescue strategies based on ketone body intervention have attracted more and more attention in the treatment of Alzheimer's disease.OBJECTIVE:To investigate whether β-hydroxybutyric acid can improve energy dysfunction by improving mitochondrial bioenergy function in HT22 cells of mouse hippocampal neurons induced by amyloid-β protein 1-42 (Aβ1-42).METHODS:HT22 cells were divided into four groups:Control,β-hydroxybutyric acid,Aβ1-42,Aβ1-42+β-hydroxybutyric acid.Related detection kits were respectively used to detect HT22 cell survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,mitochondrial membrane potential,and reactive oxygen species levels.RESULTS AND CONCLUSION:Compared with the control group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly decreased (P<0.05),and the level of reactive oxygen species was significantly increased (P<0.05) in the Aβ1-42 group.Compared with the Aβ1-42 group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly increased (P<0.05),and the reactive oxygen species level was significantly decreased (P<0.05) in the Aβ1-42+β-hydroxybutyric acid group.These results showed that β-hydroxybutyric acid improved mitochondrial bioenergetic function and ultimately improved Aβ1-42-induced energy impairment and survival rate in HT22 cells.

Obstructive sleep apnea(OSA)is a dis-order characterized by chronic intermittent hypoxia and sleep fragmentation,usually manifested by ob-struction of the upper respiratory tract,resulting in sleep fragmentation,intermittent hypoxia,and hy-percapnia.OSA and significant comorbidities are as-sociated with perioperative complications.Opioids,as the most commonly used pain relievers,may fur-ther affect perioperative pain management in OSA and comorbidities.Studies have shown that OSA patients are more susceptible to the respiratory de-pressant effects of opioids.OSA also increases the risk of opioid-induced respiratory depression.There-fore,understanding the effects and mechanisms of opioids on OSA has important clinical significance for optimizing drug use,improving prognosis,and reducing respiratory adverse events.This article aims to review the effects of opioids on OSA and their relationship.

Objective:To explore the clinical features and risk factors for pediatric severe Mycoplasma pneumoniae pneumonia (SMPP) complicated with pulmonary embolism. Methods:SMPP patients admitted to Department of Pediatrics, Jiaxing First Hospital and Pediatric Intensive Care Unit, Shanghai Children′s Hospital from December 2019 to December 2023 were included in this retrospective case-control study.According to whether they were complicated with pulmonary embolism, SMPP patients were divided into a pulmonary embolism group and a non-pulmonary embolism group.Clinical characteristics of the two groups, including general data, laboratory examination and imaging data were compared and analyzed.The t-test and Mann-Whitney rank-sum test were used to compare the measurement data, and the χ2 test was used to compare the count data.The risk factors of SMPP patients developing pulmonary embolism were analyzed by the univariate method. Results:There were 10 out of 62 SMPP children developing pulmonary embolism, showing an incidence of 16.13%.In the pulmonary embolism group, there were 5 boys and 5 girls, with a median age of 7.50 (5.75, 9.25) years.There were 52 children in the non-pulmonary embolism group, including 29 boys and 23 girls, with a median age of 6.50(5.00, 8.00)years.The hospitalization time, body temperature, total white blood cell count, neutrophil count, C-reactive protein levels, lactate dehydrogenase levels, prothrombin time, activated partial thromboplastin time, D-dimer (D-D) levels, fibrinogen degradation product levels, pleural effusion and atelectasis rates in the pulmonary embolism group were significantly higher than those in the non-pulmonary embolism group (all P<0.05). Fibrinogen levels in the pulmonary embolism group were significantly lower than those in the non-pulmonary embolism group ( P<0.05). Univariate Logistic regression analysis showed that the D-D level was a risk factor for SMPP patient developing pulmonary embolism.The receiver operating characteristic curve analysis revealed that the D-D level had the largest area under the curve for predicting pulmonary embolism of 0.990(95% CI: 0.972-1.000, P<0.001), with a sensitivity of 100%, a specificity of 92%, and a cut-off value of 4.63 mg/L. Conclusions:SMPP children complicated with pulmonary embolism are prone to high inflammation and impaired coagulation function.The increase of D-D levels is a risk factor for the development of pulmonary embolism in SMPP.

BACKGROUND:Patients with Alzheimer's disease have severe brain energy disorders.In recent years,brain energy rescue strategies based on ketone body intervention have attracted more and more attention in the treatment of Alzheimer's disease.OBJECTIVE:To investigate whether β-hydroxybutyric acid can improve energy dysfunction by improving mitochondrial bioenergy function in HT22 cells of mouse hippocampal neurons induced by amyloid-β protein 1-42 (Aβ1-42).METHODS:HT22 cells were divided into four groups:Control,β-hydroxybutyric acid,Aβ1-42,Aβ1-42+β-hydroxybutyric acid.Related detection kits were respectively used to detect HT22 cell survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,mitochondrial membrane potential,and reactive oxygen species levels.RESULTS AND CONCLUSION:Compared with the control group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly decreased (P<0.05),and the level of reactive oxygen species was significantly increased (P<0.05) in the Aβ1-42 group.Compared with the Aβ1-42 group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly increased (P<0.05),and the reactive oxygen species level was significantly decreased (P<0.05) in the Aβ1-42+β-hydroxybutyric acid group.These results showed that β-hydroxybutyric acid improved mitochondrial bioenergetic function and ultimately improved Aβ1-42-induced energy impairment and survival rate in HT22 cells.

Obstructive sleep apnea(OSA)is a dis-order characterized by chronic intermittent hypoxia and sleep fragmentation,usually manifested by ob-struction of the upper respiratory tract,resulting in sleep fragmentation,intermittent hypoxia,and hy-percapnia.OSA and significant comorbidities are as-sociated with perioperative complications.Opioids,as the most commonly used pain relievers,may fur-ther affect perioperative pain management in OSA and comorbidities.Studies have shown that OSA patients are more susceptible to the respiratory de-pressant effects of opioids.OSA also increases the risk of opioid-induced respiratory depression.There-fore,understanding the effects and mechanisms of opioids on OSA has important clinical significance for optimizing drug use,improving prognosis,and reducing respiratory adverse events.This article aims to review the effects of opioids on OSA and their relationship.

Objective:To explore the clinical features and risk factors for pediatric severe Mycoplasma pneumoniae pneumonia (SMPP) complicated with pulmonary embolism. Methods:SMPP patients admitted to Department of Pediatrics, Jiaxing First Hospital and Pediatric Intensive Care Unit, Shanghai Children′s Hospital from December 2019 to December 2023 were included in this retrospective case-control study.According to whether they were complicated with pulmonary embolism, SMPP patients were divided into a pulmonary embolism group and a non-pulmonary embolism group.Clinical characteristics of the two groups, including general data, laboratory examination and imaging data were compared and analyzed.The t-test and Mann-Whitney rank-sum test were used to compare the measurement data, and the χ2 test was used to compare the count data.The risk factors of SMPP patients developing pulmonary embolism were analyzed by the univariate method. Results:There were 10 out of 62 SMPP children developing pulmonary embolism, showing an incidence of 16.13%.In the pulmonary embolism group, there were 5 boys and 5 girls, with a median age of 7.50 (5.75, 9.25) years.There were 52 children in the non-pulmonary embolism group, including 29 boys and 23 girls, with a median age of 6.50(5.00, 8.00)years.The hospitalization time, body temperature, total white blood cell count, neutrophil count, C-reactive protein levels, lactate dehydrogenase levels, prothrombin time, activated partial thromboplastin time, D-dimer (D-D) levels, fibrinogen degradation product levels, pleural effusion and atelectasis rates in the pulmonary embolism group were significantly higher than those in the non-pulmonary embolism group (all P<0.05). Fibrinogen levels in the pulmonary embolism group were significantly lower than those in the non-pulmonary embolism group ( P<0.05). Univariate Logistic regression analysis showed that the D-D level was a risk factor for SMPP patient developing pulmonary embolism.The receiver operating characteristic curve analysis revealed that the D-D level had the largest area under the curve for predicting pulmonary embolism of 0.990(95% CI: 0.972-1.000, P<0.001), with a sensitivity of 100%, a specificity of 92%, and a cut-off value of 4.63 mg/L. Conclusions:SMPP children complicated with pulmonary embolism are prone to high inflammation and impaired coagulation function.The increase of D-D levels is a risk factor for the development of pulmonary embolism in SMPP.

microRNA(miRNA)is a 22nt long sin-gle-stranded non-coding RNA that is involved in a variety of physiological and pathological processes.Bronchial asthma is a heterogeneous disease,and airway inflammation is one of the important mecha-nisms of its pathogenesis.Asthma can be classified into different types based on the different immune mechanisms involved in its pathogenesis,and the mechanism of airway inflammation also varies be-tween different types of asthma.This article reviews the research progress of miRNA in asthma airway inflammation and endotype,and explores the pathogenesis and treatment prospects of miRNA in asthma airway inflammation and endotype.

BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.

Objective:To investigate the efficacy of high flow nasal cannula (HFNC) in children with acute respiratory failure.Methods:A prospective study was conducted. A total of 153 patients aged from 1 to 14 years with acute respiratory failure were enrolled, who were admitted to pediatric intensive care unit (PICU) of Shanghai Children′s Hospital from January 2018 to December 2019. HFNC success was defined as no need for invasive mechanical ventilation and successfully withdrawn from HFNC, while HFNC failure was defined as need for invasive mechanical ventilation. HFNC at a flow rate of 2 L/(kg·min) (maximum ≤ 60 L/min) with inhaled oxygen concentration (FiO 2) between 0.30 and 1.00 was applied to maintain percutaneous oxygen saturation (SpO 2) of 0.94-0.97. Parameters including arterial partial pressure of oxygen (PaO 2), partial pressure of carbon dioxide in artery (PaCO 2), SpO 2 and PaO 2/FiO 2 were collected before and during the application of HFNC at 1 h, 6 h, 12 h, 24 h and 48 h, as well as over 48 h after HFNC withdrawn. Comparison between the groups was performed by student ttest, Mann-Whitney U test or chi-square test. The sensitivity and specificity of the above parameters in predicting HFNC success were evaluated by receiver operating characteristic (ROC) curve. Results:A total of 153 children (70 males and 83 females) were enrolled. Among them, 131 (85.6%) cases were successfully weaned off from HFNC and 22 (14.4%) failed. The duration of HFNC was 57 (38, 95) hours in the successful group, and the PaO 2/FiO 2before HFNC application and after HFNC was withdrawn were 187 (170, 212) mmHg (1 mmHg=0.133 kPa) and 280 (262, 292) mmHg, respectively. The duration of HFNC in the failure group was 19 (9, 49) hours, and the PaO 2/FiO 2before HFNC application and after HFNC withdrawn were 176 (171, 189) mmHg and 159 (156, 161) mmHg, respectively. The values of PaO 2/FiO 2 were significantly higher in the successful group than those in the failed group at using HFNC initially 1 h (196 (182, 211) vs. 174 (160, 178) mmHg, Z =-5.105, P<0.01), 6 h (213 (203, 220) vs. 168 (157, 170) mmHg, Z =-6.772, P<0.01), 12 h (226 (180, 261) vs. 165 (161, 170) mmHg, Z =-4.308, P<0.01), 24 h (229 (195, 259) vs. 165 (161, 170) mmHg, Z=-4.609, P<0.01) and 48 h (249 (216, 273) vs. 163 (158, 169) mmHg, Z =-4.628, P<0.01) after the HFNC application, and over 48 h after HFNC was withdrawn (277 (268, 283) vs. 157 (154, 158) mmHg, Z=-3.512, P<0.01). Moreover, the PaO 2 levels were significantly higher in the successful group than those in the failed group using HFNC initially at 1 h (73.7 (71.0, 76.7) vs. 70.0 (66.2, 71.2) mmHg, Z=-4.587, P<0.01) and 6 h (79.0 (75.0, 82.0) vs. 71.0 (62.0, 72.0) mmHg, Z=-5.954, P<0.01) after HFNC application. Also, the SpO 2 levels showed the same differences at 1 h (0.96 (0.95, 0.96) vs. 0.94 (0.92, 0.94), Z =-4.812, P<0.01) and 6 h (0.96 (0.95, 0.97) vs. 0.94(0.91, 0.95), Z=-5.024, P<0.01) after HFNC application. Forty eight hours after HFNC was withdrawn, the PaO 2(88.0 (81.7, 95.0) vs. 63.7 (63.3, 66.0) mmHg, Z =-3.032, P<0.01) and SpO 2(0.96 (0.94, 0.98) vs. 0.91 (0.90, 0.92), Z=-3.957, P<0.01) were also significantly higher in the successful group. Regarding the HFNC complications, there was one case with atelectasis and one with pneumothorax in the failure group. HFNC was used as sequential oxygen therapy after extubation in 79 children, successful in all. ROC curve showed that the area under curve of PaO 2/FiO 2 in predicting HFNC success was 0.990, and the optimal cut-off value was 232 mmHg with the 95 %CI of 0.970-1.000 ( P<0.01). Conclusions:HFNC could be used as a respiratory support strategy for children with mild to moderate respiratory failure and as a sequential oxygen therapy after extubation. The PaO 2/FiO 2when HFNC withdrow is the optimal index to evaluate the success of HFNC application.

Objective To investigate the prognostic value of heart-type fatty acid-binding protein ( H-FABP) in pediatric patients with severe pneumonia complicated by acute respiratory distress syndrome ( ARDS) . Methods We performed a retrospective study to summarize the medical records of 59 pediatric patients with severe pneumonia complicated by ARDS admitted to the PICU at Shanghai Children′s Hospital between November 2016 and October 2017. According to the ratio of PaO2 to FiO2 ,the 59 cases were divided into mild-moderate ARDS group(n=47)(100 mmHg