[Predictive value of a risk prediction model guided by the ratio of respiratory rate to diaphragmatic thickening fraction for the timing of noninvasive-invasive mechanical ventilation transition in patients with acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the predictive value of a risk prediction model guided by the ratio of respiratory rate to diaphragm thickening fraction (RR/DTF) for noninvasive-invasive mechanical ventilation transition timing in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), through ultrasound evaluation of diaphragm movement indicators. METHODS: Sixty-four patients diagnosed with AECOPD and undergoing non-invasive ventilation (NIV), who were admitted to the department of critical care medicine of the First Affiliated Hospital of Jinzhou Medical University from January 2022 to July 2023 were enrolled. They were divided into NIV successful group and NIV failure group based on the outcome of NIV within 24 hours. Clinical indicators such as RR/DTF, diaphragmatic excursion (DE), tidal volume (VT), respiratory rate (RR), pH value, partial pressure of carbon dioxide (PaCO2), and sputum excretion disorder were compared between the two groups after 2 hours of NIV. The factors influencing NIV failure were included in binary Logistic regression analysis, and an RR/DTF oriented risk prediction model was established. Receiver operator characteristic curve (ROC curve) analysis was used to assess the predictive value of this model for the timing of noninvasive-invasive mechanical ventilation transition in AECOPD patients. RESULTS: Among 64 patients with AECOPD, with 43 in the NIV successful group and 21 in the NIV failure group. There were no statistically significant differences in baseline data such as age, gender, body mass index (BMI), oxygenation index (P/F), smoking history, and acute physiological and chronic health evaluation II (APACHE II) between the two groups of patients, indicating comparability. Compared to the NIV successful group, the NIV failure group showed a significantly increase in RR/DTF, RR, PaCO2, and sputum retention, while VT and DE were significantly decreased [RR/DTF (%): 1.00±0.18 vs. 0.89±0.22, RR (bpm): 21.64±3.13 vs. 19.62±2.98, PaCO2 (mmHg, 1 mmHg ≈ 0.133 kPa): 70.82±8.82 vs. 65.29±9.47, sputum retention: 57.1% vs. 30.2%, VT (mL): 308.09±14.89 vs. 324.48±23.82, DE (mm): 19.91±2.94 vs. 22.05±3.30, all P < 0.05]. Binary Logistic regression analysis showed that RR/DTF [odds ratio (OR) = 147.989, 95% confidence interval (95%CI) was 3.321-595.412, P = 0.010], RR (OR = 1.296, 95%CI was 1.006-1.670, P = 0.045), VT (OR = 0.966, 95%CI was 0.935-0.999, P = 0.044), PaCO2 (OR = 1.086, 95%CI was 1.006~1.173, P = 0.035), and sputum retention (OR = 4.533, 95%CI was 1.025-20.049, P = 0.046) were independent risk factors for predicting NIV failure in AECOPD patients. ROC curve analysis showed that the area under the curve (AUC) of 0.713 with a 95%CI of 0.587-0.839 (P = 0.005). The sensitivity was 72.73%, the specificity was 88.10%, the Youden index was 0.394, and the optimal cut-off value was 0.87. CONCLUSIONS: The RR/DTF risk prediction model has good predictive value for the timing of noninvasive-invasive mechanical ventilation transition in AECOPD patients.

Potential drug targets for myocardial infarction identified through Mendelian randomization analysis and Genetic colocalization.

Myocardial infarction (MI) is a major cause of death and disability worldwide, but current treatments are limited by their invasiveness, side effects, and lack of efficacy. Novel drug targets for MI prevention are urgently needed. In this study, we used Mendelian randomization to identify potential therapeutic targets for MI using plasma protein quantitative trait loci as exposure variables and MI as the outcome variable. We further validated our findings using reverse causation analysis, Bayesian co-localization analysis, and external datasets. We also constructed a protein-protein interaction network to explore the relationships between the identified proteins and known MI targets. Our analysis revealed 2 proteins, LPA and APOA5, as potential drug targets for MI, with causal effects on MI risk confirmed by multiple lines of evidence. LPA and APOA5 are involved in lipid metabolism and interact with target proteins of current MI medications. We also found 4 other proteins, IL1RN, FN1, NT5C, and SEMA3C, that may have potential as drug targets but require further confirmation. Our study demonstrates the utility of Mendelian randomization and protein quantitative trait loci in discovering novel drug targets for complex diseases such as MI. It provides insights into the underlying mechanisms of MI pathology and treatment.

[Predictive value of diaphragm thickening fraction and intra-abdominal pressure monitoring-oriented risk prediction model for weaning failure in patients with severe acute pancreatitis].

OBJECTIVE: To establish a risk prediction model dominated by diaphragm thickening fraction (DTF) and intra-abdominal pressure (IAP) monitoring, and to explore the predictive value of the model for weaning failure in patients with severe acute pancreatitis (SAP). METHODS: A prospective research was conducted. Sixty-three patients undergoing invasive mechanical ventilation treatment who diagnosed with SAP admitted to intensive care unit of the First Affiliated Hospital of Jinzhou Medical University from August 2020 to October 2021 were enrolled. The spontaneous breathing trial (SBT) was carried out when the clinical weaning criteria was met. The stable cardiovascular status, good pulmonary function, no chest and abdominal contradictory movement, and adequate oxygenation were defined as successful weaning. Otherwise, it was defined as failure weaning. The clinical indicators such as SBT 30-minure DTF, IAP, tidal volume (VT), respiratory rate (RR), body mass index (BMI), and blood lactic acid (Lac) were compared between the weaning success group and the weaning failure group. The indicators with statistically significant differences in the single-factor analysis were included in the secondary multivariable Logistic regression analysis to establish a risk prediction model. The correlation between the DTF and IAP at 30 minutes of SBT was analyzed. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of the risk prediction model for SAP patient withdrawal failure at 30 minutes of SBT. RESULTS: Finally, 63 patients with SAP were enrolled. Among the 63 patients, 42 were successfully weaned and 21 failed. There were no significant differences in age, gender, and oxygenation index (PaO2/FiO2), sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score at admission between the two groups, indicating that the data in the two groups were comparable. Compared with the weaning success group, IAP, RR, BMI and Lac at 30 minutes of SBT in the weaning failure group were significantly increased [IAP (mmHg, 1 mmHg ≈ 0.133 kPa): 14.05±3.79 vs. 12.12±3.36, RR (times/min): 25.43±8.10 vs. 22.02±5.05, BMI (kg/m2): 23.71±2.80 vs. 21.74±3.79, Lac (mmol/L): 5.27±1.69 vs. 4.55±1.09, all P < 0.05], while DTF and VT were significantly decreased [DTF: (29.76±3.45)% vs. (31.86±3.67)%, VT (mL): 379.00±98.74 vs. 413.60±33.68, both P < 0.05]. Secondary multivariable Logistic regression analysis showed that DTF [odds ratio (OR) = 0.758, 95% confidence interval (95%CI) was 0.584-0.983, P = 0.037], IAP (OR = 1.276, 95%CI was 1.025-1.582, P = 0.029), and RR (OR = 1.145, 95%CI was 1.014-1.294, P = 0.029) were independent risk factors for SBT withdrawal failure in 30 minutes in SAP patients. The above risk factors were used to establish the risk prediction model of aircraft withdrawal failure at 30 minutes of SBT: Logit P = -0.237-0.277×DTF+0.242×IAP+0.136×RR. Pearson correlation analysis showed that SBT 30-minute DTF was significantly correlated with IAP in SAP patients, and showed a significant positive correlation (r = 0.313, P = 0.012). The ROC curve analysis results showed that area under the ROC curve (AUC) of the risk prediction model for SAP patient withdrawal failure at 30 minutes of SBT was 0.716, 95%CI was 0.559-0.873, P = 0.003, with the sensitivity of 85.7% and the specificity of 78.6%. CONCLUSIONS: DTF, IAP and RR were independent risk factors for SBT withdrawal failure in 30 minutes in SAP patients. The DTF and IAP monitoring-oriented risk prediction model based on the above three variables has a good predictive value for weaning failure in patients with SAP.

Salidroside attenuates HALI via IL-17A-mediated ferroptosis of alveolar epithelial cells by regulating Act1-TRAF6-p38 MAPK pathway.

BACKGROUND AND PURPOSE: Hyperoxia-induced acute lung injury (HALI) is a critical life-threatening disorder characterized by severe infiltration immune cells and death of type II alveolar epithelial cells (AECII). However, little is known about the relations between immune cells and AECII in HALI. IL-17A is a pro-inflammatory cytokine mainly secreted by Th17 cells, contributing to the pathogenesis of various inflammatory diseases. The present study investigated the role of IL-17A in cell-cell communication between immune cells and AECII in HALI, and explored the therapeutic effect of salidroside (Sal, a natural anti-inflammatory agents) on HALI. METHODS: Mice with HALI were induced by exposure to hyperoxia over 90% for 12 h, 24 h, 48 h or 72 h, and the optimal timing was detected by H&E and Masson staining. Ferroptosis was confirmed by detecting the levels of MDA, Fe2+ and GPX4, and the morphological alterations of AECII under transmission electron microscopy. The expression of pro-inflammatory cytokine, including IL-6, TGF-ß1, IL-17A and IL-17A receptor (IL-17RA) were measured by Western blotting and immunohistochemical stanning. The ferroptosis-related Act1/TRAF6/p38 MAPK pathway was detected by Western blotting. The role of pro-inflammatory cytokine IL-17A for AECII ferroptosis, and the effect of Sal on HALI were investigated by administration of Y-320 (IL-17 inhibitor) and Sal respectively 3 days before mice exposed to hyperoxia. RESULTS: Mice exposed to hyperoxia for 24 h suffered sufficient HALI with inflammatory cell infiltration and collagen deposition, and exhibited features of ferroptosis under TME. Meanwhile, compared with sham mice, mice exposed to hyperoxia showed down-regulation of GPX4, and up-regulation of IL-6, TGF-ß1, IL-17A, IL-17RA, Act1, TRAF6, p38 MAPK and p-p38 MAPK. Moreover, inhibition of IL-17A with Y-320 or administration with Sal could reverse the effect caused by hyperoxia respectively. CONCLUSIONS: IL-17A is associated with immune cells infiltration in HALI, and contributes to ferroptosis of AECII that related to Act1/TRAF6/p38 MAPK pathway. Additionally, Sal protects against HALI throughout the whole pathogenic process. Video Abstract.

Oxygen inhalation has been widely used in the treatment of some diseases caused by hypoxia. This often leads people to mistakenly believe that oxygen inhalation is beneficial without harm. However, long-term high concentration oxygen inhalation will cause serious harm to the human body, sometimes even fatal. Hyperoxia causes lung cells to secrete proinflammatory factors, which promote the differentiation of infiltrated immune cells. The differentiated immune cells in turn act on lung cells and lead to their death. In short, this process is a vicious circle. Our research explores this process and is committed to finding a drug to reduce the damage of hyperoxia to the lungs when oxygen must be inhaled.

[Correlation between functional residual capacity and trans-pulmonary pressure in acute respiratory distress syndrome patients and their prognostic value].

OBJECTIVE: To analyze the application of functional residual capacity (FRC)-guided optimal positive end-expiratory pressure (PEEP) in pulmonary retention in patients with acute respiratory distress syndrome (ARDS), and to explore the correlation between FRC and trans-pulmonary pressure and their predictive value for prognosis. METHODS: Seventy-eight ARDS patients on mechanical ventilation admitted to department of critical care medicine of the First Affiliated Hospital of Jinzhou Medical University from March 2018 to May 2019 were enrolled. According to random number table method, the patients were divided into experimental group and the control group. PEEP of all patients were gradually increased in recruitment after fully sedation and analgesia. The best PEEP was set by monitoring FRC in the experimental group, and by monitoring maximum oxygen in the control group set. The differences before and after 30 minutes and 2 hours recruitment manoeuvres in dynamic compliance (Cdyn), oxygenation index (PaO2/FiO2), and mechanical power (MP) were compared between the two groups. Pearson method was used to analyze the correlation between FRC and trans-pulmonary pressure. The predictive value of FRC and trans-pulmonary pressure for 28-day mortality in patients with ARDS was analyzed by receiver operating characteristic (ROC) curve. RESULTS: The optimal PEEP was (16.24±1.57) cmH2O (1 cmH2O = 0.098 kPa) in the experimental group and (14.11±1.15) cmH2O in the control group in recruitment maneuvres, with statistically significant difference between the two groups (t = 5.678, P = 0.000). Pearson correlation analysis showed that there was a significant correlation between FRC and trans-pulmonary pressure in ARDS patients (r = 0.759, P = 0.000). Cdyn and PaO2/FiO2 in the experimental group were higher than the control group at 30 minutes and 2 hours after recruitment maneuvres [Cdyn (mL/cmH2O): 61.16±3.55 vs. 58.54±5.25, 58.59±2.82 vs. 56.86±3.40; PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 245.27±14.86 vs. 239.00±5.34, 192.25±5.11 vs. 188.86±5.07], MP was lower than the control group (J/min: 16.32±1.11 vs. 17.05±1.22, 15.22±1.25 vs. 17.03±1.50), the difference was statistically significant (all P < 0.05). The ROC curve analysis showed that both FRC and trans-pulmonary pressure had predictive value for the 28-day mortality of ARDS patients, and the area under the ROC curve (AUC) was 0.868, and 0.828 respectively (both P < 0.01). CONCLUSIONS: Measuring FRC in patients with ARDS during recruitment maneuvres can guide optimal PEEP. FRC was significantly correlated with trans-pulmonary pressure, and both of them had predictive value for 28-day mortality in ARDS patients.

[Clinical application of adaptive minute ventilation + IntelliCycle ventilation mode in patients with mild-to-moderate acute respiratory distress syndrome].

OBJECTIVE: To verify the clinical safety and efficacy of new intelligent ventilation mode adaptive minute ventilation (AMV)+IntelliCycle ventilation in patients with mild-to-moderate acute respiratory distress syndrome (ARDS). METHODS: The patients with mild-to-moderate ARDS, admitted to intensive care unit (ICU) of the First Affiliated Hospital of Jinzhou Medical University from February 2018 to February 2019, were enrolled in the study. The patients were divided into synchronous intermittent mandatory ventilation+pressure support ventilation (SIMV+PSV) group and AMV+IntelliCycle group according to the random number table method. All patients were given mechanical ventilation, anti-infection, analgesia and sedation, nutritional support and symptomatic treatment of primary disease after admission. SV800 ventilator was used for mechanical ventilation. In the AMV+IntelliCycle group, after setting the minute ventilation volume (VE), inhaled oxygen concentration (FiO2) and positive end expiratory pressure (PEEP), the ventilator was turned on the full-automatic mode, and the preset value of VE percentage was 120%. In the SIMV+PSV group, the ventilator parameters were set as follows: the ventilation frequency was 12-20 times/min, the inspiratory expiratory ratio was 1:1-2, the peak inspiratory pressure (PIP) limit level was 35-45 cmH2O (1 cmH2O = 0.098 kPa), and the setting of FiO2 and PEEP was as the same as that of AMV+IntelliCycle group, the triggering flow was set to 2 L/min. All of the clinical parameters between the two groups were compared. The main outcomes were duration of mechanical ventilation, ventilator alarm times, manual operation times, and the mechanical power; the secondary outcomes were respiratory rate (RR), VE, tidal volume (VT), PIP, mouth occlusion pressure (P0.1), static compliance (Cst), work of breathing (WOB), and time constant at 0, 6, 12, 24, 48, 72, and 120 hours; and the blood gas analysis parameters of patients before and after ventilation were recorded. RESULTS: A total of 92 patients with mild-to-moderate ARDS were admitted during the study period, excluding those who quit the study due to death, abandonment of treatment, accidental extubation of tracheal intubation and so on. Eighty patients were finally enrolled in the analysis, with 40 patients in SIMV+PSV group and AMV+IntelliCycle group respectively. (1) Results of main outcomes: compared with the SIMV+PSV mode, AMV+IntelliCycle ventilation mode could shorten the duration of mechanical ventilation (hours: 106.35±55.03 vs. 136.50±73.78), reduce ventilator alarm times (times: 10.35±5.87 vs. 13.93±6.87) and the manual operations times (times: 4.25±2.01 vs. 6.83±3.75), and decrease the mechanical power (J/min: 12.88±4.67 vs. 16.35±5.04, all P < 0.05). But the arterial partial pressure of carbon dioxide (PaCO2) of AMV+IntelliCycle group was significantly higher than that of SIMV+PSV group [mmHg (1 mmHg = 0.133 kPa): 41.58±6.81 vs. 38.45±5.77, P < 0.05]. (2) Results of secondary outcomes: the RR of both groups was improved significantly with the prolongation of ventilation time which showed a time effect (F = 4.131, P = 0.005). Moreover, compared with SIMV+PSV mode, AMV+IntelliCycle mode could maintain a better level of RR, with intervention effect (F = 5.008, P = 0.031), but no interaction effect was found (F = 2.489, P = 0.055). There was no significant difference in VE, PIP, P0.1 or Cst between the two groups, without intervention effect (F values were 3.343, 2.047, 0.496, 1.456, respectively, all P > 0.05), but they were significantly improved with the prolongation of ventilation time in both groups, with time effect (F values were 2.923, 12.870, 23.120, 7.851, respectively, all P < 0.05), but no interaction effect was found (F values were 1.571, 1.291, 0.300, 0.354, respectively, all P > 0.05). The VT, WOB or time constant in both groups showed no significant changes with the prolongation of ventilation time, and no significant difference was found between the two groups, there was neither time effect (F values were 0.613, 1.049, 2.087, respectively, all P > 0.05) nor intervention effect (F values were 1.459, 0.514, 0.923, respectively, all P > 0.05). CONCLUSIONS: AMV+IntelliCycle ventilation mode can shorten the ventilation time of patients with mild-to-moderate ARDS, reduce mechanical power, and reduce the workload of medical care, but PaCO2 in the patients with AMV+IntelliCycle mode is higher than that in the patients with SIMV+PSV mode.

Tenuigenin exhibits protective effects against LPS-induced acute kidney injury via inhibiting TLR4/NF-κB signaling pathway.

Tenuigenin (TNG) has been reported to have various pharmacological activities, such as anti-oxidative and anti-inflammatory activities. However, the protective effects of TNG on lipopolysaccharides (LPS)-induced acute kidney injury (AKI) are still not clear. The aim of this study was to investigate the protective effects and mechanism of TGN on LPS-induced AKI in mice. The kidney histological change, levels of blood urea nitrogen (BUN), and creatinine were measured to assess the protective effects of TNG on LPS-induced AKI. The levels of TNF-α, IL-1ß, and IL-6 in serum and kidney tissues were detected by ELISA. The extent of nuclear factor kappa-B (NF-κB) p65 and the expression of Toll-like receptor-4 (TLR4) were detected by western blot analysis. The results showed that TNG markedly attenuated the histological alterations, BUN and creatinine levels in kidney. TNG also suppressed LPS-induced TNF-α, IL-1ß, and IL-6 production. Furthermore, the expression of TLR4 and NF-κB activation induced by LPS were markedly inhibited by TNG. In conclusion, this study demonstrated that TNG protected against LPS-induced AKI by inhibiting TLR4/NF-κB signaling pathway.