Role of deubiquitinase OTUD1 in acute lung injury in septic mice: relationship with TAK1-MAPK signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of deubiquitinase OTUD1 in acute lung injury in septic mice and the relationship with transforming growth factor-beta activated kinase 1(TAK1)-mitogen-activated protein kinase (MAPK) signaling pathway.Methods:Twenty male wild-type (WT) and 20 OTUD1 gene knockout (KO) C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: wild-type+ sham operation group (WT-Sham group), wild-type+ sepsis group (WT-SEP group), OTUD1-KO+ sham operation group (KO-Sham group) and OTUD1-KO+ SEP group (KO-SEP group). The acute lung injury was induced by cecal ligation and perforation (CLP) in anesthetized septic mice. Mice were sacrificed at 24 h after operation, blood samples were collected from the abdominal aorta, and lung tissues were collected. Blood gas analysis was performed using the i-STAT blood gas analyzer, PaO 2 and FiO 2 were recorded, and the oxygenation index (OI) was calculated. The morphology of lung tissues was examined with a light microscope for evaluation of lung injury, and lung injury scores were calculated. The wet to dry lung weight (W/D) ratio was measured, and the activities of MPO were measured. The concentrations of TNF-α and IL-6 in plasma were detected by enzyme-linked immunosorbent assay, and the expression of OTUD1, phosphorylated TAK1 (p-TAK1), phosphorylated p38 (p-p38), phosphorylated c-Jun amino-terminal kinase (p-JNK) and phosphorylated extracellular signal-regulated kinase (p-ERK) was detected using Western blot. Results:Compared with WT-Sham group, the PaO 2 and OI were significantly decreased, the lung injury score, W/D ratio, MPO activity, and plasma TNF-α and IL-6 concentrations were increased, and the expression of OTUD1, p-TAK1, p-p38, p-JNK and p-ERK protein in lung tissues was up-regulated in WT-SEP group ( P<0.05). Compared with WT-SEP group, the PaO 2 and OI were significantly decreased, the lung injury score, W/D ratio, MPO activity, and plasma TNF-α and IL-6 concentrations were increased, and the expression of OTUD1, p-TAK1, p-p38, p-JNK and p-ERK protein in lung tissues was up-regulated in KO-SEP group ( P<0.05). Conclusions:OTUD1 is involved in the endogenous protective mechanism against acute lung injury in septic mice, which may be related to the inhibition of TAK1-MAPK signaling pathway activation and decreased inflammatory responses.

Application of video laryngoscope combined with bronchial blocker and double-lumen tube in the standardized training of anesthesia for tracheal intubation / 中华医学教育探索杂志

Objective:To explore the comparative study of video laryngoscopy combined with bronchial blocker and video laryngoscopy combined with double-lumen tube in the teaching of endotracheal intubation in thoracic surgery in the standardized residency training of anesthesia.Methods:The trainees of the standardized residency training were randomly divided into control group and experimental group for clinical teaching, with 25 ones in each group. The experimental group was treated with visual laryngoscopy combined with bronchial blocker, while the control group was treated with visual laryngoscopy combined with double-lumen tube group. The intubation time, intubation success rate, positioning time, hemodynamic changes, and complication incidence during intubation, as well as student assessment results were recorded. GraphPad Prism 6.0 was used for t test and Chi-square test. Results:The time of endotracheal intubation [(95.3±10.1) vs. (137.5±13.5)] and positioning time [(100.8±11.7) vs. (155.4±15.3)] in the experimental group were both shorter than those of the control group ( P< 0.001), the hemodynamic changes in patients with immediate intubation were smaller ( P<0.001), the success rate of intubation was higher (92% vs. 68%) ( P<0.001), the complication incidence was lower ( P<0.001) and the students' performance was higher ( P<0.001). Conclusion:In the anesthesia teaching of thoracic surgery, bronchial blocker can reduce the time of endotracheal intubation, lower the hemodynamic changes during intubation, cut down the incidence of complications, improve the success rate of endotracheal intubation and enhance the confidence of students.

Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia / 医学前沿

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R2 = 0.033; P = 0.018), followed by acute kidney injury (AKI; R2 = 0.032; P = 0.011) and plasma MIP-1β level (R2 = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.

FOXG1 Directly Suppresses Wnt5a During the Development of the Hippocampus / 神经科学通报·英文版

The Wnt signaling pathway plays key roles in various developmental processes. Wnt5a, which activates the non-canonical pathway, has been shown to be particularly important for axon guidance and outgrowth as well as dendrite morphogenesis. However, the mechanism underlying the regulation of Wnt5a remains unclear. Here, through conditional disruption of Foxg1 in hippocampal progenitors and postmitotic neurons achieved by crossing Foxg1

Short term outcomes and respiratory complications after pulmonary endarterectomy: results from a single Chinese center / 中华胸心血管外科杂志

Objective:To investigate the short term outcomes and postoperative respiratory complications of patients with chronic thromboembolic pulmonary hypertension(CTEPH) treated by pulmonary endarterectomy(PEA).Methods:45 consecutive CTEPH patients underwent PEA between December 2017 and January 2020 in our institution were enrolled, including 25 females and 20 males. The mean age of operation was 51.2(25-70) years old. 24(53.5%) patients were in New York Heart Association(NYHA) functional class Ⅲ-Ⅳ. The mean PVR before operation was 923(461-2 711) dyn·s·cm -5. All patients’ data were entered in a prospective database, divieded into patients with respiratory complications group(WRC)and without respiratory complications group(WORC). To assess risk factors for postoperative respiratory complications and its effect on short term outcomes. Results:There was a significant reduction in mPAP(from 37 mmHg to 20 mmHg) and PVR(from 923 dyn·s·cm -5 to 293 dyn·s·cm -5) in the entire group. The in-hospital mortality rate was 4.4%(2 cases), died due to postoperative cardiogenic circulatory failure, even with VA-ECMO treatment and mediastinal infection, respectively. Postoperative respiratory complications occurred in 32 patients(71.1%). The most common complications were reperfusion pulmonary edema 44.4%(20 cases) and residual pulmonary hypertension 11.1%(5 cases). The WRC group showed a tendency to have longer periods of mechanical ventilation, longer ICU stays and more ICU costs. Independent predictors of postoperative respiratory complications were time from symptom onset to PEA>36 months( OR=12.2, 95% CI: 2.1-70.7, P=0.005)and six-minute walking distance<300 m( OR=12.6, 95% CI: 1.1-138.0, P=0.0038). Conclusion:Pulmonary endarterectomy is an effective and safe treatment for CTEPH. Postoperative respiratory complications were mainly determined by symptom onset time and pre-operative status. Patients with CTEPH should consider PEA surgery early.

Role of TIPE2 in endotoxin-induced acute lung injury in mice / 中华麻醉学杂志

Objective:To evaluate the role of tumour necrosis factor-α-induced protein 8-like 2 (TIPE2) in the acute lung injury (ALI) induced by endotoxin in mice.Methods:Forty SPF healthy adult male BALB/c mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: vehicle plasmid group (VP group), vehicle plasmid plus ALI group (VP+ ALI group), TIPE2 adeno-associated virus overexpression group (T group) and TIPE2 adeno-associated virus overexpression plus ALI group (T+ ALI group). The mice in VP and VP+ ALI groups were injected with empty adeno-associated virus, while the mice in T and T+ ALI groups were intratracheally given adeno-associated virus carrying TIPE interference sequence.Three weeks later, the model of endotoxin-induced ALI was established.Lipopolysaccharide (LPS) 5 mg/kg was intratracheally given in VP+ ALI and T+ ALI groups, and the equal volume of phosphate buffered saline (PBS) was given in VP and T groups.Blood samples were obtained from the abdominal aorta at 24 h after injection of LPS for blood gas analysis, oxygenation index (OI) was calculated, and tumor necrosis factor-alpha (TNF-α) in serum were detected by enzyme-linked immunosorbent assay.The animals were then sacrificed, and lung tissues were removed for examination of pathological changes which were scored after haematoxylin and eosin staining, for calculation of the wet/dry weight ratio (W/D ratio) and for determination of myeloperoxidase (MPO) activity and the expression of TIPE2, phosphorylated c-Jun N-terminal kinase (p-JNK) and nuclear factor kappa B(NF-κB) (by Western blot). Results:Compared with VP group, the lung injury score, W/D ratio, MPO activity and concentration of serum TNF-α were significantly increased, PaO 2 and OI were decreased, expression of TIPE2 was down-regulated and expression of p-JNK and NF-κB was up-regulated in VP+ ALI group ( P<0.05). Compared with VP+ ALI group, the lung injury score, W/D ratio, MPO activity and concentration of serum TNF-α were significantly decreased, PaO 2 and OI were increased, expression of TIPE2 was up-regulated and expression of p-JNK and NF-κB was down-regulated in T+ ALI group ( P<0.05). Conclusion:The down-regulation of TIPE2 expression is involved in the process of ALI induced by endotoxin in mice.

Effects of esketamine on pyrolysis in lung tissues of rats with endotoxin-induced acute lung injury / 中华麻醉学杂志

Objective:To evaluate the effects of esketamine on pyrolysis in lung tissues of rats with endotoxin-induced acute lung injury (ALI).Methods:SPF healthy adult male Sprague-Dawley rats, weighing 200-220 g, aged 8 weeks, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), endotoxin-induced ALI group (group ALI) and esketamine group (group E). Lipopolysaccharide (LPS) 10 mg/kg was intraperitoneally injected to establish the model of endotoxin-induced ALI model.The equal volume of 0.9% sodium chloride injection was intraperitoneally injected in group C. Esketamine 10 mg/kg was intraperitoneally injected at 30 min of injection of LPS in group E. Lung tissues were removed after blood samples were collected from hearts at 24 h after injection of LPS for determination of concentrations of serum interleukin-1beta (IL-1β) and IL-8 (by enzyme-linked immunosorbent assay), the wet/dry weight ratio (W/D ratio), activities of myeloperoxidase (MPO) (by colorimetric assay) and the expression of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), caspase-1 and gasdermin D (GSDMD) (by Western blot) and for examination of pathological changes which were scored after haematoxylin and eosin staining and ultrastructure (using an electron microscope). Results:Compared with group C, the lung injury score, W/D ratio, MPO activity, expression of NLRP3, caspase-1 and GSDMD and concentrations of IL-1β and IL-18 in serum were significantly increased in ALI and E groups ( P<0.05). Compared with group ALI, the lung injury score, W/D ratio, MPO activity, expression of NLRP3, caspase-1 and GSDMD and concentrations of IL-1β and IL-18 in serum were significantly decreased in group E ( P<0.05). Conclusion:The mechanism by which esketamine reduces endotoxin-induced ALI is related with inhibition of pyrolysis in lung tissues of rats.

Role of TIPE2 in endogenous protective mechanism of acute lung injury in septic mice: relationship with TREM-1/NLRP3 inflammasome signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of tumor necrosis factor-alpha-induced protein-8 like-2 (TIPE2) in endogenous protective mechanism of acute lung injury (ALI) in septic mice and the relationship with triggering receptor expressed on myeloid cells-1 (TREM-1)/NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway.Methods:Twenty male wild-type mice and 20 TIPE2 knockout mice were divided into 4 groups using a random number table method: wild-type+ sham operation group (group WT-sham), wild-type+ ALI group (group WT-ALI), TIPE2-knockout+ sham operation group (group KO-sham) and TIPE2-knockout+ CLP group (group KO-ALI), with 10 mice in each group.The ALI model was established by cecal ligation and perforation (CLP) in septic mice.Mice were sacrificed after blood samples were obtained from the abdominal aorta at 24 h after CLP, and lung tissue specimens were obtained for microscopic examination of pathological changes (with a light microscope) which were scored and for determination of wet/dry weight ratio (W/D ratio), myeloperoxidase (MPO) activity, expression of TIPE2, TREM-1, NLRP3, caspase-1 and GSDMD (by Western blot), and concentrations of interleukin-1beta (IL-1β) and IL-18 in serum (by enzyme-linked immunosorbent assay).Results:Compared with group WT-sham, the lung injury score, W/D ratio, MPO activity and concentrations of IL-1β and IL-18 in serum were significantly increased, the expression of TREM-1, NLRP3, caspase-1 and GSDMD was up-regulated, and the expression of TIPE2 was down-regulated in group WT-ALI and group KO-ALI ( P<0.05). Compared with group WT-ALI, the lung injury score, W/D ratio, MPO activity and concentrations of IL-1β and IL-18 in serum were significantly increased, the expression of TREM-1, NLRP3, caspase-1 and GSDMD was up-regulated, and the expression of TIPE2 was down-regulated in group KO-ALI ( P<0.05). Conclusion:TIPE2 is involved in endogenous protective mechanism of ALI in septic mice, which is related to inhibition of activation of TREM-1/NLRP3 inflammasome signaling pathway.

Role of TIPE2 in endogenous protective mechanism of acute lung injury in septic mice: the relationship with TAK1/p38 MAPK/NF-κB signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of tumor necrosis factor-alpha-induced protein-8 like-2 (TIPE2) in endogenous protective mechanism of acute lung injury (ALI) in septic mice and the relationship with transforming growth factor-β-activated protein kinase (TAK1)/p38-mitogen-activated phosphokinase (p38 MAPK)/nuclear factor κB (NF-κB) signaling pathway.Methods:Sixteen male wild-type mice and 16 TIPE2-knockout mice, aged 6-8 weeks, weighing 20-25 g, were randomly divided into 4 groups: wild-type sham operation group (group WT-sham), wild-type ALI group (group WT-ALI), TIPE2-knockout sham operation group (group KO-sham) and TIPE2-knockout ALI group (group KO-ALI), with 8 mice in each group.The ALI model was established by cecal ligation and perforation (CLP) in septic mice.Mice were sacrificed at 24 h after CLP to acquire left carotid artery blood samples and lung tissue sections.Lung tissue sections were stained with hematoxylin & eosin (H&E) to examine the pathological changes and lung injury scores were assessed.Arterial blood samples were collected from the left carotid artery for blood gas analysis, and oxygenation index (OI) was calculated.Bronchoalveolar lavage fluid was collected to measure polymorphonuclear neutrophil (PMN) count.The expression of TIPE2, phosphorylated TAK1 (p-TAK1), phosphorylated p38 MAPK (p-p38) MAPK and phosphorylated NF-κB p65 (p-NF-κB p65) was detected using Western blot analysis.The levels of interleukin-1beta (IL-1β) and IL-6 in serum were determined by enzyme-linked immunosorbent assay.Results:Compared with group WT-sham, the lung injury score, PMN counts and concentrations of IL-1β and IL-6 in serum were significantly increased, the expression of p-TAK1, p-p38 MAPK and p-NF-κB p65 was up-regulated, the PaO 2 and OI were decreased, and the expression of TIPE2 was down-regulated in WT-ALI and KO-ALI groups ( P<0.05). Compared with group WT-ALI, the lung injury score, PMN counts and concentrations of IL-1β and IL-6 in serum were significantly increased, the expression of p-TAK1, p-p38 MAPK and p-NF-κB p65 was up-regulated, the PaO 2 and OI were decreased, and the expression of TIPE2 was down-regulated in group KO-ALI ( P<0.05). Conclusion:TIPE2 is involved in the endogenous protective mechanism underlying ALI in septic mice, which is related to inhibiting activation of TAK1/p38 MAPK/NF-κB signaling pathway.

Effects of esketamine on myocardial injury and relationship with Nrf2/HO-1 signaling pathway in septic rats / 中华麻醉学杂志

Objective:To evaluate the effects of esketamine on myocardial injury and the relationship with nuclear factor-erythroid 2-related factor 2 (Nrf2) heme oxygenase-1 (HO-1) signaling pathway in septic rats.Methods:Thirty-two SPF healthy adult male Sprague-Dawley rats, weighing 200-230 g, were randomized into 4 groups ( n=8 each) using a random number table method: control group (group C), control plus esketamine group (group CE), sepsis group (group S) and sepsis plus esketamine group (group SE). Lipopolysaccharide (LPS) 10 mg/kg was intraperitoneally injected to establish the sepsis model.At 30 min after LPS or normal saline intraperitoneal injection, esketamine 10 mg/kg was intraperitoneally injected, and administration was repeated 12 h later in group SE and group CE.At 24 h after LPS injection, left ventricular ejection fraction (LVEF) was measured (using echocardiography), and serum cardiac troponin I (cTnI), brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α) and high mobility group box-1 (HMGB1) concentrations were determined (by enzyme linked immunosorbent assay). Myocardial tissues were obtained for examination of pathological changes (by hematoxylin-eosin staining) and for determination of expression of Nrf2, HO-1 and transcription factor Bach 1 (BTB-CNC allogeneic 1). Results:Compared with group C, LVEF was significantly decreased, concentrations of cTnI, BNP, LDH, CK-MB, TNF-α and HMGB1 in serum were increased, expression of Nrf2 and HO-1 was down-regulated, and expression of Bach 1 was up-regulated ( P<0.05), and the significant pathological changes of myocardial tissues were found in S and SE groups.No significant change was found in the parameters mentioned above in group CE ( P>0.05). Compared with group S, LVEF was significantly increased, concentrations of cTnI, BNP, LDH, CK-MB, TNF-α and HMGB1 in serum were decreased, expression of Nrf2 and HO-1 was up-regulated, and expression of Bach 1 was down-regulated ( P<0.05), and the pathological changes of myocardium were significantly attenuated in group SE. Conclusion:Esketamine can reduce myocardial injury, and the mechanism may be related to activating Nrf2/HO-1 signaling pathway in septic rats.

Risk factors and diagnostic methods of intensive care unit-acquired weakness / 中华危重病急救医学

Objective:To explore the risk factors of intensive care unit-acquired weakness (ICU-AW) and the characteristics of Medical Research Council (MRC) score and electromyogram.Methods:A case control study was conducted. Patients with mechanical ventilation ≥ 7 days and MRC score admitted to department of respiratory and critical care medicine of China-Japan Friendship Hospital from September 2018 to January 2020 were enrolled, and they were divided into ICU-AW group (MRC score < 48) and non-ICU-AW group (MRC score ≥ 48) according to MRC score. The general situation, past medical history, related risk factors, MRC score, respiratory support mode, laboratory examination results, electromyogram examination results, ICU-AW related treatment, outcome and length of ICU stay were collected, and the differences between the two groups were compared. The risk factors of ICU-AW were analyzed by binary multivariate Logistic regression, and the characteristics of MRC score and electromyogram were analyzed.Results:A total of 60 patients were enrolled in the analysis, including 17 patients in ICU-AW group and 43 patients in non-ICU-AW group. Univariate analysis showed that there were significant differences in acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, brain natriuretic peptide (BNP), blood urea nitrogen (BUN) on the first day of ICU admission and the ratio of invasive mechanical ventilation between ICU-AW group and non-ICU-AW group [APACHEⅡ score: 21 (18, 25) vs. 18 (15, 22), SOFA score: 7 (5, 12) vs. 5 (3, 8), BNP (ng/L): 364.3 (210.1, 551.2) vs. 160.1 (66.8, 357.8), BUN (mmol/L): 9.9 (6.2, 17.0) vs. 6.0 (4.8, 9.8), invasive mechanical ventilation ratio: 88.2% vs. 46.5%, all P < 0.05]. Binary multivariate Logistic regression analysis showed no independent risk factor for ICU-AW. The average MRC score of 17 ICU-AW patients was 33±11. The limb weakness was symmetrical, and the proximal limb weakness was the main manifestation. Electromyography examination showed that the results of nerve conduction examination in ICU-AW patients mainly revealed that the amplitude of compound muscle action potential (CMAP) and sensory nerve action potentials (SNAP) were decreased, and the conduction velocity was slowed down; needle electromyography showed increased area of motor unit potential (MUP), prolonged time limit and a large number of spontaneous potentials. Prognosis evaluation showed that compared with non-ICU-AW group, patients in ICU-AW group underwent more tracheotomy (70.6% vs. 11.6%), longer length of ICU stay (days: 57±52 vs. 16±8), and more rehabilitation treatment (58.8% vs. 14.0%), and the differences were statistically significant (all P < 0.01). Conclusions:The occurrence of ICU-AW may be related to high APACHEⅡ score and SOFA score, high levels of BNP and BUN on the first day of ICU admission and the proportion of invasive mechanical ventilation, but the above factors are not independent risk factors for ICU-AW. The MRC score of ICU-AW patients was characterized by symmetrical limb weakness, mainly proximal limb weakness; in electromyography examination, the nerve conduction examination results mainly showed that CMAP and SNAP amplitude were decreased, and conduction velocity was slowed down; needle electromyography examination showed increased MUP area, prolonged duration and a large number of spontaneous potentials.

Risk factors for intracranial hemorrhage and mortality in adult patients with severe respiratory failure managed using veno-venous extracorporeal membrane oxygenation / 中华医学杂志(英文版)

BACKGROUND@#Intracerebral hemorrhage (ICH) is one of the most severe complications during veno-venous extracorporeal membrane oxygenation (VV-ECMO). This study aimed to determine the risk factors for ICH and mortality in such patients.@*METHODS@#We analyzed the clinical data of 77 patients who received VV-ECMO due to severe respiratory failure from July 2013 to May 2019 at China-Japan Friendship Hospital. Demographical data, laboratory indices, imaging characteristics, and other clinical information were collected. Multivariable logistic regression analyses were performed to identify risk factors for ICH and mortality.@*RESULTS@#Of 77 patients, 11 (14.3%) suffered from ICH, and 36 (46.8%) survived. The survival rate was significantly lower (18.2% [2/11] vs. 51.5% [34/66], P = 0.040) in patients with ICH than in those without ICH. Multivariable analysis revealed that factors independently associated with ICH were diabetes mellitus (adjusted odds ratio [aOR]: 12.848, 95% confidence interval [CI]: 1.129-146.188, P = 0.040) and minimum fibrinogen during ECMO (aOR: 2.557, 95% CI: 1.244-5.252, P = 0.011). Multivariable analysis showed that factors independently associated with mortality were acute hepatic failure during ECMO (aOR: 9.205, 95% CI: 1.375-61.604, P = 0.022), CO2 retention before ECMO (aOR: 7.602, 95% CI: 1.514-38.188, P = 0.014), and minimum platelet concentration during ECMO (aOR: 0.130, 95% CI: 0.029-0.577, P = 0.007).@*CONCLUSIONS@#Diabetes mellitus and minimum fibrinogen concentration during ECMO are risk factors for ICH in patients with severe respiratory failure managed using VV-ECMO. This indicated that anticoagulants use and nervous system monitoring should be performed more carefully in patients with diabetes when treated with VV-ECMO due to severe respiratory failure.

Relationship between TIPE2 and caspase-11 during pyroptosis in macrophages of mice / 中华麻醉学杂志

Objective@#To evaluate the relationship between tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) and caspase-11 during pyroptosis in macrophages of mice.@*Methods@#J774A.1 macrophages of mice were divided into 4 groups (n=6 each) using a random number table method: non-specific siRNA (Scr-siRNA) group (S group), Scr-siRNA plus LPS/ATP group (S+ LPS/ATP group), TIPE2-siRNA group (T group) and TIPE2-siRNA plus LPS/ATP group (T+ LPS/ATP group). The corresponding siRNA and Lipofectamine2000 transfection reagents were added to each group, and transfection was performed for 24-48 h, and in addition LPS 1.0 μg/ml was then added, cells were incubated for 5 h, then ATP 5.0 mmol/L was added, and cells were incubated for 1 h in S+ LPS/ATP and T+ LPS/ATP groups.Cells were collected to detect the expression of TIPE2, caspase-11, NOD-like receptor familypyrin domain containing 3 (NLRP3) and caspase-1 (by Western blot). The supernatant was collected for determination of lactic dehydrogenase (LDH) and myeloperoxidase (MPO) activities and concentrations of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay).@*Results@#Compared with group S, the expression of TIPE2 was significantly down-regulated, the expression of caspase-11, NLRP3 and caspase-1 was up-regulated, and the activities of LDH and MPO and concentrations of IL-1β and IL-18 in supernatant were increased in group S+ LPS/ATP (P<0.05). Compared with group T, the expression of TIPE2 was significantly down-regulated, the expression of caspase-11, NLRP3 and caspase-1 was up-regulated, and the activities of LDH and MPO and concentrations of IL-1β and IL-18 in supernatant were increased in group T+ LPS/ATP (P<0.05). Compared with group S+ LPS/ATP, the expression of TIPE2 was significantly down-regulated, the expression of caspase-11, NLRP3 and caspase-1 was up-regulated, and and the activities of LDH and MPO and concentrations of IL-1β and IL-18 in supernatant were increased in group T+ LPS/ATP (P<0.05).@*Conclusion@#TIPE2 inhibits pyroptosis in macrophages through down-regulating the expression of caspase-11 in mice.

Effect of penehyelidine hydrochloride on TIPE2-TLR4-MyD88 signaling pathway in a rat model of traumatic acute lung injury / 中华麻醉学杂志

Objective@#To evaluate the effect of penehyelidine hydrochloride (PHCD) on tumor necrosis factor α-induced protein 8-like-2 (TIPE2)-Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88) signaling pathway in a rat model of traumatic acute lung injury (ALI).@*Methods@#Thirty SPF healthy male Sprague-Dawley rats, aged 8 weeks, weighing 190-210 g, were divided into 3 groups (n=15 each) by a random number table method: sham operation group (group Sham), traumatic ALI group (group ALI) and group PHCD.ALI was induced by blunt chest trauma in ALI and PHCD groups.PHCD 2 mg/kg was intraperitoneally injected immediately after blunt chest trauma in group PHCD.The rats were sacrificed and lung tissues were removed at 8 h after the model was successfully established for examination of the pathological changes and ultrastructure of lung tissues (with a light microscope or an electron microscope) and for determination of the wet to dry weight ratio (W/D ratio) and expression of TLR4 and MyD88 in lung tissues.@*Results@#Compared with group Sham, the W/D ratio was significantly increased, TIPE2 expression was down-regulated, and the expression of TLR4 and MyD88 was up-regulated in ALI and PHCD groups (P<0.05). Compared with group ALI, the W/D ratio was significantly decreased, TIPE2 expression was up-regulated, and the expression of TLR4 and MyD88 was down-regulated (P<0.05), and the pathological changes of lung tissues and ultrastructure were significantly attenuated in group PHCD.@*Conclusion@#The mechanism by which PHCD reduces traumatic AIL is related to activating TIPE2-TLR4-MyD88 signaling pathway in rats.

Effect of penehyelidine hydrochloride on TIPE2-TLR4-MyD88 signaling pathway in a rat model of traumatic acute lung injury / 中华麻醉学杂志

Objective To evaluate the effect of penehyelidine hydrochloride(PHCD)on tumor necrosis factor α-induced protein 8-like-2(TIPE2)-Toll-like receptor 4(TLR4)-myeloid differentiation fac-tor 88(MyD88)signaling pathway in a rat model of traumatic acute lung injury(ALI).Methods Thirty SPF healthy male Sprague-Dawley rats,aged 8 weeks,weighing 190-210 g,were divided into 3 groups(n＝15 each)by a random number table method: sham operation group(group Sham),traumatic ALI group(group ALI)and group PHCD.ALI was induced by blunt chest trauma in ALI and PHCD groups.PHCD 2 mg/kg was intraperitoneally injected immediately after blunt chest trauma in group PHCD.The rats were sacrificed and lung tissues were removed at 8 h after the model was successfully established for exami-nation of the pathological changes and ultrastructure of lung tissues(with a light microscope or an electron microscope)and for determination of the wet to dry weight ratio(W/D ratio)and expression of TLR4 and MyD88 in lung tissues.Results Compared with group Sham,the W/D ratio was significantly increased,TIPE2 expression was down-regulated,and the expression of TLR4 and MyD88 was up-regulated in ALI and PHCD groups(P＜0.05).Compared with group ALI,the W/D ratio was significantly decreased,TIPE2 expression was up-regulated,and the expression of TLR4 and MyD88 was down-regulated(P＜0.05),and the pathological changes of lung tissues and ultrastructure were significantly attenuated in group PHCD.Conclusion The mechanism by which PHCD reduces traumatic AIL is related to activating TIPE2-TLR4-MyD88 signaling pathway in rats.

Relationship between TIPE2 and caspase-11 during pyroptosis in macrophages of mice / 中华麻醉学杂志

Objective To evaluate the relationship between tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) and caspase-11 during pyroptosis in macrophages of mice.Methods J774A.1 macrophages of mice were divided into 4 groups (n =6 each) using a random number table method:nonspecific siRNA (Scr-siRNA) group (S group),Scr-siRNA plus LPS/ATP group (S+LPS/ATP group),TIPE2-siRNA group (T group) and TIPE2-siRNA plus LPS/ATP group (T+LPS/ATP group).The corresponding siRNA and Lipofectamine2000 transfection reagents were added to each group,and transfection was performed for 24-48 h,and in addition LPS 1.0 μg/ml was then added,cells were incubated for 5 h,then ATP 5.0 mmol/L was added,and cells were incubated for 1 h in S + LPS/ATP and T + LPS/ATP groups.Cells were collected to detect the expression of TIPE2,caspase-11,NOD-like receptor familypyrin domain containing 3 (NLRP3) and caspase-1 (by Western blot).The supernatant was collected for determination of lactic dehydrogenase (LDH) and myeloperoxidase (MPO) activities and concentrations of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay).Results Compared with group S,the expression of TIPE2 was significantly down-regulated,the expression of caspase-11,NLRP3 and caspase-1 was up-regulated,and the activities of LDH and MPO and concentrations of IL-1β and IL-18 in supernatant were increased in group S+LPS/ATP (P＜0.05).Compared with group T,the expression of TIPE2 was significantly down-regulated,the expression of caspase-11,NLRP3 and caspase-1 was up-regulated,and the activities of LDH and MPO and concentrations of IL-1β and IL-18 in supernatant were increased in group T+LPS/ATP (P＜0.05).Compared with group S+LPS/ATP,the expression of TIPE2 was significantly down-regulated,the expression of caspase-11,NLRP3 and caspase-1 was up-regulated,and and the activities of LDH and MPO and concentrations of IL-1β and IL-18 in supernatant were increased in group T+LPS/ATP (P＜0.05).Conclusion TIPE2 inhibits pyroptosis in macrophages through down-regulating the expression of caspase-11 in mice.

Clinical features and influence factors of pregnancy-induced hypertension with renal impairment at high altitude / 中华肾脏病杂志

Objective To investigate the incidence and clinical features of women with hypertension disorders of pregnancy complicated with renal impairment at high altitude,and explore the impact of proteinuria,renal insufficiency and preexisting chronic kidney disease (CKD) on these patients.Methods A pool of 1790 pregnant women admitted to Yunnan Diqing Tibetan Autonomous Prefecture People's Hospital from September 2017 to September 2018.Data of 123 patients who met the criteria of hypertension disorders in pregnancy were collected and retrospectively studied.Their clinical characteristics and pregnancy outcomes were analyzed.Patients with hypertension and renal impairment,simple hypertension patients as well as normal pregnant women were compared.Hypertensive patients with proteinuria,renal insufficiency (Scr ＞ 70 μmol/L) and preexisting CKD were also compared with simple hypertension patients.The impact of proteinuria,renal insufficiency and preexisting CKD on patients with hypertension disorders of pregnancy was assessed by multivariate logistic analysis.Results Of these 123 patients,61 cases (49.6％) had renal impairment,57 cases (46.3％) had proteinuria,15 cases (12.2％)had renal insufficiency and 6 cases (4.9％) had preexisting CKD.Compared with normal pregnant women and simple hypertension patients,patients with hypertension and renal impairment had higher blood pressure,Scr,primipara rate and caesarean section rate (all P ＜ 0.05),lower gestational age,neonatal Apgar scores and plasma albumin level (all P ＜ 0.05),as well as adverse pregnancy outcomes,including premature birth,stillbirth/neonatal death,intrauterine growth restriction,infants of low-birth weight and admission to the neonatal intensive care unit (NICU) (all P ＜ 0.05).The clinical features and pregnancy outcomes of 57 patients with proteinuria correlated with the proteinuria.Compared with non-nephrotic syndrome patients and patients without proteinuria,patients with nephrotic syndrome (NS) had lower plasma albumin level and higher rates of premature birth,infants of low-birth weight and admission to NICU (all P ＜ 0.05).Among 15 patients with renal insufficiency,there were 13 mild abnormal cases (70 μmol/L ＜ Scr≤ 123 μmol/L,86.7％).Compared with those with normal renal function,patients with renal insufficiency had higher Scr,uric acid and rates of preeclampsia/eclampsia,intrauterine growth restriction,infants of low-birth weight and admission to NICU,while lower plasma albumin level (all P ＜ 0.05).Among 6 patients with preexisting CKD,4 had NS,2 had renal insufficiency,5 delivered before 37 weeks,and 2 infants died.Logistic regression analysis showed that NS (0R=4.863,P=0.032),renal insufficiency (OR=7.550,P=0.017) and systolic pressure (OR=1.061,P=0.002) were independent risk factors for adverse pregnancy outcomes among patients with hypertension disorders in pregnancy.Conclusions Renal impairment is common among patients with hypertension disorders in pregnancy at high altitude and has adverse effects on pregnancy outcomes.Massive proteinuria,renal insufficiency and systolic pressure are risk factors for these patients.

Effect of penehyclidine hydrochloride on expression of caveolin-1 during LPS-induced lung injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the expression of caveolin-1 (Cav-1) with lipopolysaccharide (LPS)-induced lung injury (LI) in rats.Methods Thirty SPF healthy male Sprague-Dawley rats,weighing 170-190 g,were divided into 3 groups (n =10each) using a random number table method:control group (group C),LPS-induced LI group (group LI)and PHCD group.LI was produced by injecting LPS 0.2 ml (5 mg/kg) via the trachea in anesthetized rats.PHCD 0.5 ml (2 mg/kg) was intraperitoneally injected at 1 h before establishing the model in group PHCD.Arterial blood samples were collected at 24 h after establishing the model for blood gas analysis and for determination of serum tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) concentrations by enzyme-linked immunosorbent assay.Rats were then sacrificed,and the lungs were removed.The main bronchus was lavaged,and the broncho-alveolar lavage fluid (BALF) was collected for calculation of the percentage of polymorphonuclear neutrophils (PMNs).Lung tissues were obtained for examination of pathological changes and for determination of myeloperoxidase (MPO) activity (by colorimetric assay),wet/dry weight ratio (W/D ratio),and expression of Cav-1 and nuclear factor kappa B (NF-sB) in nucleoprotein (by Western blot).Results Compared with group C,pH value and PaO2 were significantly decreased,the PaCO2,percentage of PMNs in BALF,W/D ratio and MPO activity were increased,the Car-1 expression was down-regulated,the expression of NF-κB in nucleoprotein was up-regulated,and the serum TNF-α and IL-1β concentrations were increased in group LI (P＜0.05).Compared with group LI,pH value and PaO2 were significantly increased,the PaCO2,percentage of PMNs in BALF,W/D ratio and MPO activity were decreased,the Cav-1 expression was up-regulated,the expression of NF-κB in nucleoprotein was down-regulated,and the serum TNF-α and IL-1β concentrations were decreased (P＜0.05),and the path ological changes of lung tissues were significantly attenuated in group PHCD (P＞0.05).Conclusion The mechanism by which PHC reduces LPS-induced LI may be related to up-regulating the expression of Cav-1 and mitigating inflammatory responses in lung tissues of rats.

Effects of dexmedetomidine on NLRP3 inflammasome during acute lung injury induced by blunt chest trauma and hemorrhagic shock-resuscitation in rats / 中华麻醉学杂志

Objective To evaluate the effects of dexmedetomidine on NLRP3 inflammasome during acute lung injury ( ALI ) induced by blunt chest trauma and hemorrhagic shock-resuscitation in rats. Methods Forty-five SPF healthy male Sprague-Dawley rats, weighing 200-220 g, were divided into 3 groups (n=15 each) using a random number table method: sham operation group (Sham group), ALI group and dexmedetomidine group ( Dex group) . A rat model of ALI was established by blunt chest trauma and hemorrhagic shock-resuscitation. Dexmedetomidine 5 μg·kg-1 ·h-1 was infused into the femoral vein after blunt chest trauma in Dex group. Blood samples were collected from the femoral artery at 6 h after blunt chest trauma for measurement of arterial oxygen partial pressure and concentrations of pro-inflammatory cytokines interleukin-1beta ( IL-1β) and IL-18 in serum ( by enzyme-linked immunosorbent assay ) . The oxygenation index was calculated. The rats were sacrificed and lungs were removed for examination of the pathological changes which were scored and for determination of the expression of NLRP3, caspase-1 and apoptosis-associated speck-like protein containing CARD ( ASC) in lung tissues ( by Western blot) and ac-tivities of lactic dehydrogenase ( LDH) and myeloperoxidase ( MPO) in lung tissues ( by colorimetry) . Re-sults Compared with Sham group, PaO2 and oxygenation index were significantly decreased, the expres-sion of NLRP3, caspase-1 and ASC was up-regulated, the activities of LDH and MPO were increased, and the concentrations of IL-1β and IL-18 in serum were increased in ALI group ( P＜0. 05 ) . Compared with ALI group, PaO2 and oxygenation index were significantly decreased, the expression of NLRP3, caspase-1 and ASC was down-regulated, the activities of LDH and MPO were decreased, and the concentrations of IL-1β and IL-18 in serum were decreased in ALI group ( P＜0. 05) . Conclusion Dexmedetomidine can al-leviate blunt chest trauma and hemorrhagic shock-resuscitation induced ALI in rats, and the mechanism is related to inhibition of NLRP3 inflammasome activation and reduction of inflammatory response.

Role of TIPE2 in pyroptosis in macrophage of mice: evaluation using siRNA technique / 中华麻醉学杂志

Objective To evaluate the role of tumor necrosis factor α-induced protein 8-like-2 ( TIPE2) in pyroptosis in macrophage of mice using small interfering RNA ( siRNA) technique. Methods J774A. 1 macrophages of mice were divided into 4 groups ( n=6 each) using a random number table method: non-specific siRNA (Scr-siRNA) group (S group), Scr-siRNA plus LPS∕ATP group (S+LPS∕ATP group ) , TIPE2-siRNA group ( T group ) and TIPE2-siRNA plus LPS∕ATP group ( T+LPS∕ATP group) . The corresponding siRNA and Lipofectamine2000 transfection reagents were added to each group, and transfection was performed for 24-48 h, and in addition LPS 1. 0 μg∕ml was then added, cells were incubated for 5 h, then ATP 5. 0 mmol∕L was added, and cells were incubated for 1 h in S+LPS∕ATP and T+LPS∕ATP groups. Cells were collected to detect the expression of TIPE2, NOD-like receptor familypyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain ( ASC) and Gasdermin D ( GSDMD) ( by Western blot) . The superna-tant was collected for determination of lactic dehydrogenase ( LDH) activity and concentrations of interleu-kin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results Compared with group S, the expression of TIPE2 was significantly down-regulated, the expression of NLRP3, caspase-1, ASC and GSDMD was up-regulated, and the LDH activity and concentrations of IL-1βand IL-18 in supernatant were increased in group S+LPS∕ATP ( P<0. 05) . Compared with group T, the expression of TIPE2 was sig-nificantly down-regulated, the expression of NLRP3, caspase-1, ASC and GSDMD was up-regulated, and the LDH activity and concentrations of IL-1βand IL-18 in supernatant were increased in group T+LPS∕ATP (P<0. 05). Compared with group S+LPS∕ATP, the expression of TIPE2 was significantly down-regulated, the expression of NLRP3, caspase-1, ASC and GSDMD was up-regulated, and the LDH activity and con-centrations of IL-1βand IL-18 in supernatant were increased in group T+LPS∕ATP ( P<0. 05) . Conclusion Application of siRNA technique once again confirms that TIPE2 can inhibit pyroptosis in macrophages of mice.