Acute respiratory distress syndrome (ARDS) is a common critical disease in clinic, which refers to acute hypoxic respiratory failure caused by various insults, with bilateral fluffy infiltrates on chest radiography. It is reported that gender may play a critical role in the occurrence, severity, and outcomes of ARDS. Nevertheless, gender difference in ARDS is still controversial because of the complexity of the disease. This paper summarized the sex difference in epidemiology of ARDS according to different etiologies such as sepsis, trauma and respiratory viruses, and discussed gender-bias in the occurrence, severity and outcomes of ARDS. Moreover, we clarified briefly the mechanism that may contribute to the gender-bias to provide novel ideas for clinical treatment of ARDS.

Objective:To construct and verify the occurrence model of acute respiratory distress syndrome (ARDS) using lung injury prediction score (LIPS) combined with acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and oxygenation index (PaO 2/FiO 2). Methods:Using a prospective cohort study method, 244 patients with complete medical records who were admitted to the intensive care unit (ICU) of Peking University Third Hospital from December 2020 to July 2022 were selected as research objects according to the inclusion and exclusion criteria. They were divided into training set (173 cases) and validation set (71 cases). Patients' gender, age, body mass index (BMI), various causes (shock, sepsis, craniocerebral injury, pulmonary contusion, multiple trauma, aspiration, pneumonia, acute abdomen, hypoproteinemia, acidosis, major surgery, etc.), underlying diseases (diabetes, malignant tumor, cerebrovascular disease, liver disease, kidney disease) and laboratory test indicators were collected. According to the above data, the LIPS score, APACHE Ⅱ score, sequential organ failure assessment (SOFA) and PaO 2/FiO 2, etc within 24 hours after admission to the ICU were calculated. Univariate analysis was used to screen the influencing factors for the occurrence of ARDS, and the factors with P < 0.2 were included in the multivariate Logistic regression analysis to screen out the independent predictive factors for the occurrence of ARDS. According to the results of multivariate Logistic regression analysis, the risk score of patients with ARDS was obtained to construct the risk prediction model of ARDS, the receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated. The established ARDS prediction model was externally validated, and ROC curves were drawn to evaluate the predictive accuracy of the prediction model for the occurrence of ARDS in critically ill patients, and the AUC of the validation set was calculated to analyze the predictive performance of each risk factor on the occurrence of ARDS. Results:A total of 173 patients were enrolled in the training set, including 121 patients without ARDS and 52 patients with ARDS; 77 cases of acute abdomen, 64 cases of sepsis, 60 cases of shock, 51 cases of acidosis, 40 cases of hypoproteinemia, 37 cases of diabetes, 34 cases of craniocerebral injury, 34 cases of abnormal liver function, 28 cases of multiple trauma, 23 cases of malignant tumor, 23 cases of spinal orthopedic surgery, 17 cases of obesity, 12 cases of pneumonia, 11 cases of pulmonary contusion, and 7 cases of chronic kidney disease, chemotherapy in 6 cases, and aspiration in 2 cases. The rates of shock, sepsis, acute abdomen, acidosis, abnormal liver function, lung contusion, pneumonia and aspiration, gender, age, LIPS score, APACHE Ⅱ score, and SOFA score in the ARDS group were significantly higher than those in the non-ARDS group (all P < 0.05), moreover, PaO 2/FiO 2 ratio was significantly lower than that of non-ARDS group ( P < 0.01). Multivariate Logistic regression analysis showed that LIPS score, APACHE Ⅱ score, and PaO 2/FiO 2 ratio were independent risk factors for ARDS in ICU patients with high risk factors for ARDS, and the odds ratio ( OR) was 1.768 [95% confidence interval (95% CI) was 1.380-2.266], 1.242 (95% CI was 1.089-1.417), 0.985 (95% CI was 0.978-0.991), all P < 0.05. ROC curve analysis showed that the AUC of the ARDS prediction model training set was 0.920, the sensitivity was 86.5%, and the specificity was 86.8%; the AUC of the verification set was 0.896, the sensitivity was 96.8%, and the specificity was 76.6%. Conclusion:LIPS score, APACHE Ⅱ score and PaO 2/FiO 2 are independent risk factors for the occurrence of ARDS in ICU patients with high risk factors for ARDS. The ARDS risk prediction model established based on these three indicators has a good predictive ability for the occurrence of ARDS in critically ill patients, wihich needs to be verified by multicenter cohort studies.

Acute?lung?injury?(ALI)?and?its?severe?form,?acute?respiratory?distress?syndrome?(ARDS),?are?common?critical?syndromes.?The?causes?of?the?syndrome?are?complex?and?diverse.?The?main?pathological?features?are?the?diffuse?inflammatory?and?protein-rich?pulmonary?edema?caused?by?destruction?of?the?blood-air?barrier.?Reactive?oxygen?species?(ROS)?mediate?oxidative?damage?by?oxidizing?bio-macromolecules,?including?lipids,?proteins?and?nucleic?acid.?Among?many?systems?producing?ROS,?nicotinamide-adenine?dinucleotide?phosphate?(NADPH)?oxidase-mediated?ROS?is?the?main?source,?and?its?functional?subunit?is?the?transmembrane?subunit?NOX?family.?The?distribution?of?NOX?family?proteins?in?lung?tissue?is?cell?type?dependent.?NOX-derived?ROS?is?involved?in?the?defense?function?of?lung?tissue?and?related?to?the?occurrence?and?development?of?ALI/ARDS.?This?review?mainly?describes?the?cell?distribution,?activation?factors,?and?its?relationship?with?the?occurrence?and?development?of?ALI?of?the?NOX?family.

Acute respiratory distress syndrome (ARDS), characterized by acute hypoxic respiratory dysfunction or failure, is a manifestation of multiple organ failure (MOF) in the lung, which often caused by various non-cardiac reasons, included severe trauma, infection, shock; and the most common risk factor is sepsis which would cause uncontrolled host response to infecting factors. As a strong stressor during sepsis, the severe infectious state of the body triggers serious stress reaction. The hypothalamus-pituitary-adrenal cortical (HPA) axis and sympathetic-adrenal medulla axis were activated and participated the initiation and progression of the stress response through the production of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), epinephrine and norepinephrine (NE). As the main hormones during sepsis, catecholamines (CA), including epinephrine and NE, could bind to adrenergic receptor (AR). After the binding, CA could play its role through the complicated signal way. Therefore, to explore the signal transduction pathway of α-AR, during sepsis, is important for revealing the mechanism of sepsis-induced ARDS.

Objective To explore the effects and mechanism of α2A-adrenergic receptor (α2A-AR) antagonist BRL-44408 maleate on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Methods Sixty male C57BL/6 mice were randomly divided into three groups (n = 20): sham group, LPS group and BRL-44408 maleate pre-treated group (BRL+LPS group). The model of ALI was replicated by intratracheally administrated of LPS (5 mg/kg), and the mice in the sham group were received an equal volume of saline. Mice in the BRL+LPS group were treated with additionally BRL-44408 maleate (5 mg/kg, i.p) at 4 hours before LPS administration. The mice were sacrificed at 6 hours and 24 hours after LPS administration in each group. Among them, 5 mice were used to collect the bronchoalveolar lavage fluid (BALF) and the other 5 mice were sacrificed for lung tissues. The levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-10) in BALF were measured by enzyme linked immunosorbent assay (ELISA). The level of protein in BALF was measured by bicinchoninic acid (BCA) method. The histopathological changes and wet/dry (W/D) ratio of lung tissue were observed. The expression of lung phosphorylated mitogen-activated protein kinase kinase (p-MEK) and phosphorylated extracellular regulated protein kinases (p-ERK) were detected by Western Blot. Results Compared with the sham group, the lung histopathological injury was significantly aggravated, and the histopathological injury score was significantly increased, the lung W/D ratio, and total protein content, NE, TNF-α, IL-6, IL-10 in BALF, and p-MEK and p-ERK expressions were significantly increased in LPS group at 6 hours after model setup [the lung histopathological injury score: 0.70±0.04 vs. 0.14±0.13,W/D ratio: 4.79±0.15 vs. 4.35±0.17, protein content (g/L): 1.51±0.36 vs. 0.46±0.13, NE (ng/L): 85.02±11.28 vs.47.18±10.30, TNF-α (ng/L): 186.61±21.93 vs. 9.18±2.86, IL-6 (ng/L): 193.45±26.54 vs. 13.58±2.54, IL-10 (ng/L): 113.46±31.23 vs. 25.66±9.41, p-MEK/β-actin: 0.246±0.019 vs. 0.178±0.030, p-ERK/β-actin:0.257±0.013 vs. 0.175±0.014, all 1 < 0.05], and increase with time after model setup. Compared with the LPS group,BRL-44408 maleate pretreatment for 6 hours could significantly improve the degree of lung injury and reduce the lung histopathological injury score (0.61±0.05 vs. 0.70±0.04), reduce lung W/D weight ratio (4.51±0.22 vs. 4.79±0.15);the expression of NE, TNF-α, IL-6 in BALF were inhibited [NE (ng/L): 55.77±15.86 vs. 85.02±11.28, TNF-α (ng/L): 54.79±12.68 vs. 186.61±21.93, IL-6 (ng/L): 67.66±20.08 vs. 193.45±26.54], in addition, the up-regulation of p-MEK, p-ERK were significantly inhibited (p-MEK/β-actin: 0.204±0.008 vs. 0.246±0.019, p-ERK/β-actin:0.186±0.024 vs. 0.257±0.013), with statistically significant differences (all 1 < 0.05). The protein content and the expression of IL-10 in BALF showed no significant difference. Conclusion α2A-AR blocker BRL-44408 maleate could alleviate endogenous ALI induced by LPS in mice by inhibiting the MEK/ERK pathway.

Objective:To evaluate the efficacy of roxatidine and omeprazolein on preventing gastrointestinal bleeding in critically ill patients.Methods:A prospective cohort study was conducted in adult patients admitted to an intensive care unit (ICU), who had risk factors for stress related mucosal disease (SRMD), and had an estimated stay of no less than 5 days and mechanical ventilation for more than 48 h. Patients were randomized into the experiment group (Roxatidine 75 mg IV Q12 h) and control group (Omeprazole 40 mg IV Q12 h). Demographic data, acute physiology and chronic health score (APACHEⅡ) and SOFA score on day 1 were collected, intragastric pH values were tested every 2 hours for the first 5 days, the daily average of pH and proportion of patients with average pH≥4 were calculated. Stool occult blood were detected at day 1 and bacterial culture of gastric juice were performed before medication administration and on day 5 after medication administration. The implementation of enteral nutrition support, situation of gastrointestinal hemorrhage and adverse effects were analyzed. Furthermore, length of hospital stay and mortality in ICU and on the 28th day were acquired. SPSS 22.0 software was used for data analysis. Consecutive data were expressed as mean and standard deviation, categorical data were expressed as frequencies (percentage). Comparison of measurement data between groups was performed by analysis of variance or rank sum test. Comparison of count data between groups was performed by the Chi-square test. P<0.05 was regarded as statistically significant. Results:A total of 91 patients were recruited and randomly separated into experimental group ( n=46) and control group ( n=45) from October 2017 to March 2018. There were no statistical differences in gender, age, body mass index (BMI), enteral nutrition status, APACHEⅡ and SOFA score on day 1 between the two groups (all P>0.05). Roxatidine in the experiment group rapidly increased the intragastric pH to ≥4.0 and continued to stabilize at pH ≥4.0 during the monitoring period. Omeprazole increased and maintained intragastric pH≥5.0. The proportion of patients with average pH≥4.0 was 82.5% in the second 24 hours in the experiment group, and stably increased to 90% on day 5. There were no significant differences between groups in gastrointestinal bleeding, length of hospital stay, and mortality in ICU and on 28th day(all P> 0.05). No drug related adverse effects occurred during the study period. Logistic-regression analysis did not screen for risk factors of SRMD. Conclusions:Roxatidine acetate hydrochloride can rapidly elevate and maintain the gastric pH above 4.0, and has similar efficacy and safety as omeprazole in inhibiting gastric acid secretion and preventing SRMD with gastrointestinal bleeding.