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 effect of open-lung strategy (OLS) on postoperative delirium (POD) in elderly patients undergoing laparoscopic surgery.Methods:Seventy-four elderly patients of both sexes, aged 65-80 yr, with body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective laparoscopic radical rectal cancer or radical prostate cancer surgery under general anesthesia, were divided into 2 groups ( n=37 each) by the random number table method: OLS group and non-OLS (NOLS) group. Patients in OLS group received small tidal volume ventilation, recruitment maneuvers, and individualized positive end-expiratory pressure. Fixed positive end-expiratory pressure 5 cmH 2O was given in NOLS group. Cerebral regional oxygen saturation (rSO 2), pH value, PaO 2, PaCO 2 and PaO 2/FiO 2 were recorded before induction of anesthesia (T 0, baseline value), at 10 min after tracheal intubation (T 1), at 1 and 2 h after pneumoperitoneum (T 2, 3) and at 10 min after extubation (T 4). The levels of serum interleukin-6 (IL-6), IL-10 and calcium-binding protein (S100β) were measured by enzyme-linked immunosorbent assay before surgery, at the end of surgery, and at 1 day after surgery. The development of POD was assessed using the delirium assessment scale at 1-3 days after surgery. Results:Compared with NOLS group, the pH value was significantly decreased at T 3, PaCO 2 was increased, PaO 2, PaO 2/FiO 2 and rSO 2 were increased at T 2-4, serum IL-6 and S100β concentrations were decreased after surgery and at 1 day after surgery, the serum IL-10 concentration was increased, and the incidence of POD was decreased in OLS group ( P<0.05). Conclusions:OLS can increase rSO 2, reduce the systemic inflammatory response, and decrease the risk of POD in elderly patients undergoing laparoscopic surgery.

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.

Objective:To evaluate the effect of open-lung strategy (OLS) on cardiopulmonary function in frail elderly patients undergoing laparoscopic surgery.Methods:Eighty-four frail elderly patients aged 65-80 yr, with body mass index of 18.5-30.0 kg/m 2, of American Society of Anesthesiologists physical status Ⅱor Ⅲ, with preoperative Fried frailty phenotype scale score ≥3, undergoing elective laparoscopic radical rectal cancer or radical prostate cancer surgery under general anesthesia, were divided into 2 groups ( n=42 each) by the random number table method: OLS group and non-OLS group (NOLS group). The patients underwent recruitment maneuvers and individualized positive end-expiratory pressure (PEEP) in OLS group, while patients received fixed PEEP (5 cmH 2O) in NOLS group.At 10 min after endotracheal intubation (T 0, baseline value), immediately after the peak of recruitment maneuvers (T 1), 30 min (T 2) and 1 h (T 3) after individualized PEEP setting and 10 min before the end of surgery (T 4), cardiac function indexes were measured by transoesophageal echocardiography, optic nerve sheath diameter was measured, and the arterial blood gas analysis indexes and pulmonary function indexes were recorded.The levels of serum cardiac troponin T, creatine kinase-MB and precursor of type B natriuretic peptide were determined by chemiluminescence before surgery and at 1 and 2 days after surgery.The postoperative pulmonary complications within 7 days after surgery and postoperative outcomes were also recorded. Results:Eighty-one patients were finally enrolled, with 41 in NOLS group and 40 in OLS group.Compared with NOLS group, the left ventricular end diastolic area, left ventricular ejection fraction, stroke volume, ratio of early mitral flow velocity to early mitral annulus velocity, mitral annular plane systolic excursion, left ventricular global longitudinal strain, right ventricular end diastolic area, right ventricular fractional area change, tricuspid annular plane systolic excusion and right ventricular global longitudinal strain were significantly decreased at T 1, 2 ( P<0.05), and no significant change was found in the indices mentioned above at the remaining time points ( P>0.05), PaO 2, oxygenation index, and lung compliance were increased at T 1-4, PaCO 2 and alveolar arterial partial pressure difference of oxygen were decreased, the total incidence of pulmonary complications was reduced within 7 days after operation, and the duration of postanesthesia care unit stay, time to first out-of-bed activity and postoperative length of hospital stay were shortened ( P<0.05), and no significant change was found in optic nerve sheath diameter and concentrations of serum cardiac troponin T, creatine kinase-MB, and precursor of type B natriuretic peptide at each time point in OLS group ( P>0.05). Conclusions:OLS can improve lung function in frail elderly patients, which is helpful for patient prognosis without causing negative cardiac effects, and can be safely used for intraoperative airway management in frail elderly patients without obvious cardiac dysfunction.

Objective:To investigate the value of modified early warning score (MEWS) combined with D-dimer test in the establishment of an acute pancreatitis severity evaluation model.Methods:The clinical data of 357 patients with acute pancreatitis who received treatment in the Second Affiliated Hospital of Anhui Medical University, China between January 2017 and December 2018 were collected for this study. The receiver operating characteristic curve was used to determine the optimal cut-off value of MEWS combined with D-dimer test for predicting non-mild acute pancreatitis. The relationship between MEWS and D-dimer level was analyzed using regression analysis. The area under the curve (AUC) was used to evaluate the ability of each factor to predict the severity of acute pancreatitis. The sensitivity and specificity of the new model to predict non-mild acute pancreatitis were calculated.Results:According to the receiver operating characteristic curve, the AUC of D-dimer, MEWS, and new model were 0.702, 0.628 and 0.734 respectively ( P < 0.05). The AUC of the new model in predicting non-mild acute pancreatitis was significantly higher than that of MEWS and D-dimer test (0.734 > 0.702 > 0.628, Z = 3.20, P < 0.01). Conclusion:The ability of the new model established based on MEWS and D-dimer to predict the severity of acute pancreatitis is stronger than that of each of MEWS and D-dimer. The new model is simple, convenient and more suitable for clinical use.

Objective:To compare the efficacy and safety between WangShiBaoChiWan and mosapride in the treatment of functional dyspepsia (FD).Methods:From September 2019 to September 2020, patients with postprandial fullness and early satiation who met the Rome Ⅳ criteria for FD diagnosis were enrolled from 15 hospitals, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical College. The subjects were randomly divided into WangShiBaoChiWan (experimental) group and mosapride (control) group in the ratio of 1∶1. The treatment regimens were WangShiBaoChiWan+ mosapride simulator, WangShiBaoChiWan simulator+ mosapride, respectively with a treatment period of 2 weeks. The primary efficacy outcome was the improvement rates of main symptoms before and after treatment, the secondary efficacy primary efficacy outcome was the total clinical effective rate and the change of the single symptom score. And the safety indicator included adverse events. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:A total of 251 FD patients were enrolled in the full analysis set, including 124 in the experimental group and 127 in the control group; 241 FD patients were in the per-protocol analysis set, including 117 in the experimental group and 124 in the control group. The analysis of per-protocol analysis set showed that the improvement rates of the main symptoms of the experimental group and the control group were (66±29)% and (60±30)%, respectively, and the difference was not statistically significant ( P>0.05). The improvement rate of the main symptoms of the experimental group reached 117% of that of the control group, which exceeded the expected non-inferiority standard of 80%. The total clinical effective rates of the experimental group and the control group were 76.07% (89/117) and 75.81% (94/124), respectively, and the difference was not statistically significant ( P>0.05). The results of full analysis set showed that the incidence of adverse events of the experimental group and the control group was 1.62% (2/124) and 1.57% (2/127), respectively, and the difference was not statistically significant ( P>0.05). There were no serious adverse events in the two groups. Conclusion:The improvement rate of the main symptoms of WangShiBaoChiWan is not inferior to that of mosapride in the treatment of FD, and it has good safety.

Objective Respiratory Syncytial Virus (RSV) fusion protein is an important transmembrane glycoprotein associated with virus infection and immunity.To clarify the genetic characteristics and antigenic sites variation in F protein,comprehensive analysis was performed with 61 RSV stains isolated in Beijing area.Methods The antigenic sites area of F protein gene of RSV was amplified by RT-PCR and sequenced.The Phylogenetic trees were constructed with MEGA program.The identity matrices and genetic sites variation were determined with Bioedit software.Results Pairwise nucleotide (amino acid) sequences identities were 95.9％-100％ (98.3％-100％) among 43 subtype A,97.5％ -100％ (98.7％-100％) among 18 subtype B,and 83.2％-84.9％ (93.1％-95.1％) between groups A and B,respectively.Phylogenetic analyses revealed that all the strains could be divided into two groups.Further,group A could be divided into 6 clusters,and group B could be divided into 3 clusters.There were 7 and 4 amino acid changes at group A and group B,respectively.Variations at antigenic site (Φ) were observed in amino residues 209 and 211.No more mutation was found on the antigenic sites area except the 276 (N→S) on palivizumab binding site.Conclusions The nucleotide and amino acid have high identity in F protein of Beijing RSV isolates except a few mutations.The F protein remains the potential candidate of RSV vaccine and molecular drugs.

Objective:To investigate the mechanism of activation of NOD-like receptors protein (NLRP)3 in the process of human adenovirus type 7 (HAdV-7) infection.Methods:THP-1 cells were treated with adenosine triphosphate (ATP), an NLRP3 inhibitor MCC950, and a caspase-1 inhibitor Ac-YVDK-cmk, ammonium pyrrolidinedithiocarbamate (APDC), N-acetyl-L-cysteine (NAC), cathepsin B-selective inhibitor CA-074-me, glibenclamide and potassium chloride (KCl) respectively. THP-1 cells without infection were used as the control group and those infected with HAdV-7 were used as the experimental group. The expression of NLRP3, caspase-1 and IL-1β in the supernatant was detected by enzyme-linked immunosorbent assay (ELISA), Q-PCR and western blot(WB).Results:Immunofluorescence detection showed that HAdV-7 infected THP-1, while WB showed that HAdV-7 infection could induce the pro-IL-1β protein expression in cells, and caspase-1 cleavage induce IL-1β maturation and release to the outside of cells. The expression of IL-1β in the supernatant of cells was significantly increased as detected by ELISA (MOI=0.5, P=0.0008). After inhibition of caspase-1 expression, the expression of IL-1 β in the supernatant was significantly inhibited ( P=0.0025). The expression of pro-IL-1β and NLRP3 mRNA in HAdV-7 infected cells was up-regulated (NLRP3: P=0.0004; pro-IL-1β: P=0.0007), and WB showed that HAdV-7 could up regulate the expression of pro-IL-1β and NLRP3 protein in the cells. After THP-1 was treated with NLRP3 specific inhibitor MCC950 the expression of IL-1β in the supernatant of HAdV-7 infected cells were significantly inhibited ( P=0.002) 7). Toll-like receptor (TLR)2, TLR4 and TLR7/9 signal transduction inhibitors were used respectively to inhibit HAdV-7 infection of THP-1. The result showed that TLR4 signal transduction was inhibited, and the expression level of IL-1 β in cell supernatant was significantly decreased ( P=0.0122). Using reactive oxygen species (ROS) inhibitor, cathepsin B inhibitor, or K + outflow inhibitor to inhibit the infection of THP-1 differentiated macrophages by HAdV-7, the result showed that when cathepsin B was inhibited ( P=0.0292), or K + outflow was inhibited (KCl, P=0.0022; glibenclamide, P=0.0275), the expression level of IL-1 β in the supernatant was significantly decreased. Conclusions:HAdV-7 infection of THP-1 cells can activate NLRP3 inflammasome. The first signal of NLRP3 activation is transmitted by TLR4, and the second signal is mainly activated by K + outflow and cathepsin B release.

Objective:To evaluate a multiplex fluorescent probe real-time PCR kit in the viral pathogen detection among children with acute lower respiratory tract infections.Methods:This study used multiplex fluorescent probe real-time PCR method to detect viral pathogens in 300 nasopharyngeal swabs from children with acute lower respiratory tract infection in Beijing Children′s Hospital (influenza A/B virus, respiratory syncytial virus, adenovirus, parainfluenza virus type I and parainfluenza virus type ⅡI), and liquid chip method was used for comparison. In addition, 136 positive-nasopharyngeal aspirates determined by immunofluorescence test were verified by the multiplex fluorescent probe real-time PCR method .Results:For the 300 nasopharyngeal swabs, 173 and 159 were determined positive by real-time PCR and liquid chip kit, respectively. In addition, real-time PCR method found 22 cases of mixed infection samples with two or more viral pathogens compared with the immunofluorescence method .Conclusions:The multiplex fluorescent probe real-time PCR method has high sensitivity and specificity, and has good application value for the detection of children′s acute lower respiratory tract viral pathogens.