［Abstract］　Objective　To analyze the effects of airway pressure release ventilation(APRV) and low tidal volume ventilation(LTV) on inflammation in acute respiratory distress syndrome(ARDS), and to explore the effects and mechanisms of different mechanical ventilation modes on the related mechanical stress in ARDS. Methods　An adult Bama miniature pig model of severe ARDS was constructed, and LTV and APRV ventilation modes were applied for mechanical ventilation treatment for 48 hours. The model pigs were divided into blank control group(control group, n=3), disease control group(ARDS group, n=3), LTV mechanical ventilation group(LTV group, n=4) and APRV mechanical ventilation group(APRV group, n=4). The effects of the two ventilation modes on oxygenation index and inflammatory factors were observed. High-throughput sequencing was performed on lung tissues, and the effects of the differential gene integrin beta 4(ITGB4) on inflammation after mechanical ventilation for ARDS were verified at the protein level. The APRV-like stretching model and the LTV-like stretching model were constructed by using the A549 cell line, and 4-hour stretch test was performed in vitro. The effects of the two stretching modes on the secretion of inflammatory cytokines were explored by ITGB4. Small interfering ribonucleic acid(RNA)(siRNA) was used for silencing the expression of ITGB4, and the differences in the expression of the ITGB4-focal adhesion kinase(FAK)-p38-mitogen-activated protein kinase(MAPK)-interleukin-8(IL-8)(ITGB4-FAK-p38-MAPK-IL-8) pathway was compared between the LTV+siRNA group and the APRV+siRNA group. The p38 inhibitor of SB203580 was used to intervene the cells, and the difference in the level of IL-8 expression was compared between the LTV+SB203580 group and the APRV+SB203580 group. Results　After successful modeling of severe ARDS and 48-hour ventilation, the levels of IL-6 and IL-8 in the alveolar lavage fluid and lung tissues in the APRV group were significantly lower than those in the LTV group(P<0.05). However, there were no statistically significant differences in IL-1 and tumor necrosis factor-α(TNF-α) between the two groups(P>0.05). The results of high-throughput sequencing in transcriptome showed the significant enrichment of extracellular matrix(ECM)-receptor interaction pathway and focal adhesion signaling pathway after mechanical ventilation. In the lung tissues, the levels of ITGB4, p-FAK, p-p38 protein expressions in the APRV group were significantly lower than those in the LTV group(P<0.05). In the cell stretching model, LTV and APRV-like stretches were repeated in vitro cells, and cyclic stretching for 4 hours resulted in a significant increase in cellular IL-8 levels(P<0.05), but did not significantly change the level of IL-6(P>0.05). The levels of IL-8, ITGB4, p-FAK and p-p38 expressions in the APRV group were significantly lower than those in the LTV group(P<0.05). Silencing ITGB4 could significantly down-regulate the levels of p-FAK and p-p38 expressions in the APRV group and the LTV group after mechanical stretching, and the down-regulation trend was obvious in the APRV+siRNA group, but there were no statistically significant differences in the down-regulations between the APRV+siRNA group and the LTV+siRNA group(P>0.05). After the use of p38 inhibitor, the level of p-p38 phosphorylation in the APRV+SB203580 group was significantly down-regulated compared with that in the LTV+SB203580 group(P=0.032). Conclusion　APRV mechanical ventilation mode significantly improves the secretion of inflammatory factor IL-8 after severe ARDS through the ITGB4-p38-MAPK pathway, which may provide a potential intervention target for the treatment of ARDS.]]> 2024/3/15 0:00:00 1, WEI Canzheng^1,2*, DONG Meiling¹, CHENG Jiangli¹, Haiyier Buick Adali¹, QIN Yiwei^1,3, XUE Yang¹, GAO Hui¹, ZHAO Lican¹, LI Jianbo¹, ZHOU Yongfang¹, WANG Bo¹, YANG Jing^1#, KANG Yan^1,4]]> MA Aijia¹, WEI Canzheng^1,2*, DONG Meiling¹, CHENG Jiangli¹, Haiyier Buick Adali¹, QIN Yiwei^1,3, XUE Yang¹, GAO Hui¹, ZHAO Lican¹, LI Jianbo¹, ZHOU Yongfang¹, WANG Bo¹, YANG Jing^1#, KANG Yan^1,4 4true ［Abstract］　Objective　To analyse the effect of the activation of adenosine A_2B receptor(A_2BR) on sepsis-induced acute lung injury(ALI) and to explore its regulatory role in pulmonary microvascular endothelial inflammation injury. Methods　(1)A total of 24 Sprague-Dawley(SD) rats were randomly divided into sham operation group(sham group), ALI model group(ALI group), A_2BR agonist BAY60-6583 intervention group(ALI+BAY group), and A_2BR inhibitor PSB1115 intervention group(ALI+PSB group), with 6 rats in each group. The rats were sacrificed 24 hours after modeling, and their lung tissues were collected. Lung injury score(Smith score) was obtained under light microscopy, and lung wet/dry mass ratio(W/D) was calculated. Alveolar fluid clearance(AFC) rate was detected by Evans Blue staining. The levels of inflammatory factors in lung tissues including tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β) were detected by enzyme-linked immunosorbent assay(ELISA). (2)TNF-α-induced human pulmonary microvascular endothelial cells(HPMECs) injury model was used. The control group, TNF-α group, BAY group, PSB group, BAY+TNF-α group and PSB+TNF-α group were set up. After 24 hours of cell culture, fluorescein isothiocyanate(FITC)-albumin assay was used to detect the monolayer permeability of HPMECs in each group, and the levels of IL-1β, intercellular adhesion molecule-1(ICAM-1), vascular endothelial-cadherin(VE-cadherin) and angiopoietins(ANGPT) expressions were detected by Werstern blot. Results　Compared with the sham group, the ALI group showed significantly increased Smith score, lung W/D, and levels of TNF-α, IL-6 and IL-1β in lung tissues, and showed significantly decreased AFC. Compared with the ALI group, the ALI+BAY group showed significantly decreased Smith score, lung W/D, and levels of TNF-α, IL-6 and IL-1β in lung tissues, and showed significantly increased AFC. However, the ALI+PSB group showed the opposite results. In the TNF-α-induced HPMECs injury model, compared with the control group, the TNF-α group showed the increased levels of IL-1β and ICAM-1 expressions, and the increased monolayer permeability of HPMECs, and the decreased levels of VE-cadherin and ANGPT expressions. Compared with the TNF-α group, the BAY+TNF-α group showed the decreased levels of IL-1β and ICAM-1 expressions and the decreased monolayer permeability of HPMECs, and the increased levels of VE-cadherin and ANGPT expressions. However, pretreatment with PSB1115 could reverse the above phenomenon. The differences among the above groups were statistically significant(P<0.05). Conclusion　Activation of A_2BR can attenuate sepsis-induced ALI and exert protective effects by reducing pulmonary microvascular endothelial inflammation, reducing permeability and promoting angiogenesis pathways.]]> 2024/3/15 19:12:41 WANG Huixia, AN Youzhong 3true ［Abstract］　Objective　To study the correlation of arterial blood gas-related indicators with dorsal lung ventilation and abnormal pulmonary blood flow in acute brain injury(ABI) patients complicated with acute respiratory distress syndrome(ARDS) by using electrical impedance tomography(EIT). Methods　The data of pulmonary ventilation and pulmonary blood flow monitored by EIT in 12 patients complicated with ARDS after ABI who were admitted to the Department of Intensive Care Medicine of Zhongshan Hospital of Fudan University from May 2020 to December 2021, and the patients′ arterial blood gas and inflammation-related clinical indicators during this period were collected. According to the sum of the patients′ dorsal ventilation regions of interest(ROI)(ROI3+ROI4), they were divided into low level of dorsal ventilation group(n=6) and high level of dorsal ventilation group(n=6) with median as the boundary. According to the level of partial pressure of carbon dioxide in artery(PaCO₂), the patients were divided into PaCO₂ hypoventilation group(n=6) and PaCO₂ hyperventilation group(n=6) with the median as the boundary point. A correlation analysis was performed between the sum of the patients′ dorsal ventilation ROI and lactic acid and other indicators, and the patient′s dead space, shunt fraction, and ventilation-perfusion matching level under EIT were calculated. Results　In the patients complicated with ARDS after ABI, a negative correlation was found between the sum of EIT dorsal ventilation(ROI3+ROI4) and lactic acid level in arterial blood(r=-0.700, P=0.011). The were no significant differences in arterial blood gas indicators and inflammation-related indicators between the low level of dorsal ventilation group and the high level of dorsal ventilation group(P>0.05). There were no significant differences in arterial blood gas indicators and inflammation-related indicators between the PaCO₂ hypoventilation group and the PaCO₂ hyperventilation group(P>0.05). According to the available EIT pulmonary ventilation and perfusion imaging data from 5 cases, the patients′ average level of ventilation-perfusion matching was (49±11)%(<60%), indicating that there was a significant mismatch in pulmonary ventilation-perfusion. Conclusion　In the patients complicated with ARDS after ABI, there is a significant imbalance in ventilation-perfusion matching in them, and detection of lactic acid level in arterial blood can be used to monitor the status of dorsal ventilation.]]> 2024/3/15 19:12:41 1, ZHENG Xin^2*, ZHONG Ming¹]]> WANG Huan¹, ZHENG Xin^2*, ZHONG Ming¹ 2true ［Abstract］　Objective　To explore the value of matrix metalloproteinase-9(MMP-9) in early diagnosis and prognostic evaluation of patients with acute respiratory distress syndrome(ARDS) complicated with septic shock. Methods　A total of 113 ARDS patients admitted to the People′s Hospital of Guangxi Zhuang Autonomous Region from April 2020 to April 2023 were selected as the study subjects. The patients were divided into ARDS complicated with septic shock group(61 cases) and ARDS non-septic shock group(52 cases) according to the occurrence of shock within 24 hours after they were diagnosed with ARDS. A total of 22 healthy volunteers were selected as the normal control group during the same period. The patients in the ARDS complicated with septic shock group were divided into survival group(27 cases) and death group(34 cases) according to their outcomes 28 days after treatment. The general data and the level of MMP-9 expression in each group were compared. Receiver operating characteristic(ROC) curve was used to evaluate the accuracy of MMP-9 in the early diagnosis of ARDS complicated with septic shock patients. Logistic regression analysis was used to explore the influencing factors of prognosis of the ARDS complicated with septic shock patients. Results　The level of MMP-9 expression in the ARDS complicated with septic shock group and the ARDS non-septic shock group was higher than that in the normal control group, and the level of MMP-9 expression in the ARDS non-septic shock group was higher than that in the ARDS complicated with septic shock group, and the differences were statistically significant(P<0.05). The results of ROC curve analysis showed that MMP-9 could effectively predict the occurrence of ARDS complicated with septic shock［AUC(95%CI)=0.666(0.565-0.767)］, and the optimal cut-off value was 28.53 ng/mL, and the corresponding sensitivity and specificity were 47.50% and 94.20%, respectively. The results of multivariate logistic regression analysis showed that MMP-9［OR(95%CI)=0.976(0.954-0.999)］, oxygenation index［OR(95%CI)=0.978(0.957-1.000)］ and interleukin-6(IL-6)［OR(95%CI)=1.004(1.000-1.008)］ were influencing factors for death in the ARDS complicated with septic shock patients(P<0.05). The results of ROC curve analysis showed that MMP-9 could effectively predict the prognosis of the ARDS complicated with septic shock patients［AUC(95%CI)=0.735(0.605-0.865)］, and the optimal cut-off value was 33.83 ng/mL, and the corresponding sensitivity and specificity were 70.59% and 77.78%, respectively. Conclusion　MMP-9 has good value in early diagnosis of ARDS complicated with septic shock, and has a certain predictive effect on the severity and prognosis of ARDS complicated with septic shock patients.]]> 2024/3/15 0:00:00 1, XIANG Shulin^2*, XIONG Bin¹, HAN Lin¹, PANG Jing¹, JIANG Lingyu¹, JI Debin³, WANG Han³, HUANG Zhen³, REN Yanwen³]]> HU Miao¹, XIANG Shulin^2*, XIONG Bin¹, HAN Lin¹, PANG Jing¹, JIANG Lingyu¹, JI Debin³, WANG Han³, HUANG Zhen³, REN Yanwen³ 1true