FTO attenuates LPS-induced acute kidney injury by inhibiting autophagy via regulating SNHG14/miR-373-3p/ATG7 axis.

N6-methyladenosine (m6A) is a master driver of RNA function and implicates in the pathogenesis of renal injury. LncRNA SNHG14 is highly expressed in sepsis patients with acute kidney injury (AKI) and aggravates kidney cell dysfunction. This study aimed to explore whether demethylase FTO affect m6A methylation of SNHG14 in AKI injury and its underlying mechanism. The expression level of FTO was obviously downregulated in sepsis-associated AKI patients compared with normal controls. Mechanistically, FTO overexpression impeded SNHG14 expression by decreasing the stability of SNHG14 in an m6A-dependent manner in LPS-induced HK-2 cells. Additionally, FTO overexpression inhibited cell autophagy and apoptosis while promoting cell viability of LPS-induced HK-2 cells. Moreover, overexpression of FTO inhibited SNHG14 expression and autophagy in LPS-induced AKI mice. Functionally, SNHG14 acts as a competing endogenous RNA (ceRNA) via directly sponging miR-373-3p in LPS induced HK-2 cells. Additionally, miR-373-3p directly targets ATG7. Inhibition of SNHG14 suppresses NF-κB signaling pathway and production of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) via miR-373-3p/ATG7 in LPS-induced HK-2 cells. Furthermore, the SNHG14/miR-373-3p/ATG7 interaction network contributes to the regulatory effect of FTO on LPS-induced HK-2 cell viability, apoptosis and autophagy. These results suggested demethylase FTO suppressed the m6A modification of lncRNA SNHG14 and inhibits autophagy in LPS-induced AKI via regulating miR-373-3p/ATG7, which provided an important novel perspective for understanding sepsis-associated AKI and is conducive for developing new therapeutic targets and strategies.

[Retracted] MicroRNA­153 is a prognostic marker and inhibits cell migration and invasion by targeting SNAI1 in human pancreatic ductal adenocarcinoma.

Subsequently to the publication of the above article, a concerned reader drew to the Editors' attention that the cell invasion and migration assay data shown in Fig. 3B and D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that these contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 34: 595­602, 2015; DOI: 10.3892/or.2015.4051].

The rate of acute kidney injury (AKI) alert detection by the attending physicians was associated with the prognosis of patients with AKI.

Introduction: Early identification of AKI was always considered to improve patients' prognosis. Some studies found that AKI early warning tools didn't affect patients' prognosis. Therefore, additional studies were necessary to explore the reasons. Methods: This study was a secondary analysis of a multicenter randomized controlled trial that found electronic health record warnings for AKI did not influence patients' prognoses. Univariate, multivariate, subgroup, curve fitting, and threshold effect analysis were used to explore the association between AKI warnings detected by attending physicians and the patient's prognosis. Results: A total of 6,030 AKI patients were included in the study. The patients were classified into two groups based on the rate of AKI alerts detected by attending physicians: the partial group (n = 5,377), and the complete group (n = 653). In comparison to the partial group, the complete group significantly decreased 14-day AKI progression, 14-day dialysis, and 14-day mortality, with adjusted ORs of 0.48 (0.33, 0.70), 0.26 (0.09, 0.77), and 0.53 (0.33, 0.84) respectively, and the complete group significantly improve the discharge to home, with an OR value of 1.50 (1.21, 1.87). When the rate of AKI alerts detected by the attending physicians as a continuity variable, we found that the rate of alerts seen by attending physicians was associated with 14-day mortality and the discharge to home, with adjusted ORs of 1.76 (1.11, 2.81) and 1.42 (1.13, 1.80). The sensitivity analysis, curve-fitting analysis, and threshold effect analysis also showed that the rate of alert seen by the attending physician was correlated with the patient's prognosis. Conclusion: The rate of AKI alert detection by attending physician were related to the patient's prognosis. The higher the rate of AKI alert detection by attending physicians, the better the prognosis of patients with AKI.

Nomogram Models for Predicting Delirium of Patients in Emergency Intensive Care Unit: A Retrospective Cohort Study.

Background: Intensive care unit (ICU) delirium is one of the most common clinical syndromes that results in many adverse events that affect patients, families, and hospitals. To date, there has been no tool for effectively predicting the occurrence of delirium in emergency intensive care unit (EICU) patients. Methods: We conducted a retrospective cohort study and constructed a prediction model for 319 patients in EICU, who met our inclusion criteria. We analyzed the relationship between patients' clinical data within 24 hours of admission and delirium, applied univariate and multivariate logistic regression analyses to select the most relevant variables for construction of nomogram models, then applied bootstrapping for internal validation. Results: A total of five variables, namely stomach and urinary tubes, as well as sedative, mechanical ventilation and APACHE-II scores, were selected for model construction. We generated a total of five sets of models (three sets of construction models and two sets of internal verification models), with similar predictive value. The optimal model was selected, and together with the 5 variables used to construct a nomogram. The AUC of the MFP model in all patients was 0.76 (0.70, 0.82), whereas that in non-elderly patients (<60 years old) for the full model was 0.83 (0.74, 0.91). In elderly patients (≥60 years old), the AUC of the MFP model was 0.82 (0.73, 0.91). Conclusion: Overall, the five-marker-based prognostic tool, established herein, can effectively predict the occurrence of delirium in EICU patients.

Pyroptosis regulators exert crucial functions in prognosis, progression and immune microenvironment of pancreatic adenocarcinoma: a bioinformatic and in vitro research.

Pyroptosis is an inflammatory programmed cell death, showing potentials to be a novel anti-cancer approach. However, the roles of pyroptosis-related (PR) genes (PRGs) in pancreatic adenocarcinoma (PAAD) remain elusive. In the present study, we constructed a novel PR risk signature through the lasso regression analysis. The risk signature was greatly conducive to PAAD prognostic assessment. PR risk score was identified as an independent prognostic factor and could distinguish the prognostic differences of most clinical subgroups. Meanwhile, it could improve the traditional prognostic models based on TNM-staging. Next, its prognostic value was also tested in five validation cohorts. Using CIBERSORT, ESTIMATE, and ssGSEA algorithms, the effects of PR risk signature on tumor immune microenvironment (TIM) were explored. High PR risk suppressed antitumor immune through decreasing the infiltrating levels of CD8 T and NK cells. The genomic information and histological expression of risk PRGs were uncovered by USCA and HPA databases. Somatic mutation, methylation alteration, and homozygous CNV of eight PRGs barely occurred in PAAD samples. As for therapeutic correlation, PR risk score may not predict the efficacy of PD-1/L1 inhibitors and was weakly associated with multiple drug susceptibilities. Finally, the biofunctions of toll like receptor 3 (TLR3) in pancreatic cancer (PC) cells were investigated through qPCR, MTT, colony formation, and Transwell assays. Overexpression of TLR3 could promote the proliferation, migration, and invasion of PC cells. In conclusion, PRGs play crucial roles in prognosis, progression, and immune microenvironment of PAAD. TLR3 is expected to be a promising therapeutic target.

Predictors of Mortality in Hospitalized COVID-19 Patients Complicated With Hypotension and Hypoxemia: A Retrospective Cohort Study.

Introduction: COVID-19 patients with hypotension and hypoxemia had a significantly worse outcome. The purpose of this research was to ascertain the risk factors affecting the prognoses of these patients and to develop appropriate prognostic prediction tools. Methods: From March 1, 2020, to April 16, 2020, a retrospective cohort analysis of COVID-19 patients with hypotension and hypoxemia was performed. The univariate and multivariate analyses were performed to identify the associated risk factors influencing the prognosis of COVID-19 patients with hypotension and hypoxemia, and the selected variables were then utilized to construct and validate the prediction model for these patients. Results: Three hundred and twenty-seven COVID-19 patients with hypotension and hypoxemia who met the inclusion and exclusion criteria were included in this study. Age, temperature, troponin, and blood glucose were related to mortality in COVID-19 patients with hypotension and hypoxemia in both univariate and multivariate analyses. The MFP model (multiple fractional polynomial model), full model, and stepwise model were utilized to build the prediction model, and their AUCs were, respectively, 0.902 (0.868, 0.936), 0.902 (0.868, 0.936), and 0.902 (0.868, 0.936). Because the sample size for this research was limited, we utilized bootstrapping for internal validation. The AUCs of Bootstrap full and Bootstrap stepwise were 0.902 (0.867, 0.936) and 0.902 (0.868, 0.936), respectively. Conclusion: Age, temperature, troponin, and blood glucose levels were associated with mortality in COVID-19 patients with hypotension and hypoxemia. Additionally, the prediction model developed using the variables above showed a high predictive value for predicting the prognosis of these individuals.

A Nomogram to Predict the 28-day Mortality of Critically Ill Patients With Acute Kidney Injury and Treated With Continuous Renal Replacement Therapy.

BACKGROUND: Acute kidney injury (AKI) is a severe and common complication in critically ill patients and is associated with increased morbidity and mortality. At present, there is not a tool to predict the prognosis of critically ill patients with AKI and treated with continuous renal replacement therapy (CRRT). METHODS: A retrospective cohort study was to construct a prediction model for the 28-day mortality of patients with AKI and treated with CRRT. From January 2009 to September 2016, A total of 846 cases were included in our study. RESULTS: A total of five variables selected by multi-factor Cox regression analysis were used to constructed three predictive models and adopted bootstrapping for internal validation. Finally, we get five sets of models (three sets of construction models and two sets of internal verification models) with similar predictive value. The stepwise model, which including four variables (CCI score, Alb, Phosphate (24h) and SOFA score), was the simplest model, so we chose it as our final predictive model and constructed a nomogram based on it. The area under the ROC curve (AUC) of the stepwise model and the stepwise bootstrap model (BS stepwise) were respectively 0.78(0.75,0.82) and 0.78 (0.75,0.82). The AUC of the stepwise model and the BS stepwise in patients with sepsis were 0.77 (0.73,0.81) and 0.77 (0.73,0.81). The AUC of the stepwise model and the BS stepwise in patients without sepsis were 0.83 (0.78,0.89) and 0.83 (0.78,0.89). CONCLUSIONS: We developed a four-marker-based prognostic tool that could effectively predict each individual's 28-day mortality for patients with AKI and treated with CRRT.

SOFA score is superior to APACHE-II score in predicting the prognosis of critically ill patients with acute kidney injury undergoing continuous renal replacement therapy.

BACKGROUND: Acute kidney injury (AKI) is the most common cause of organ failure in multiple organ dysfunction syndrome (MODS) and is associated with increased mortality. This study aimed at determining the efficacy of sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE-II) scoring systems in assessing the prognosis of critically ill patients with AKI undergoing CRRT. METHODS: The predictive value of SOFA and APACHE-II scores for 28- and 90-d mortality in patients with AKI undergoing continuous renal replacement therapy (CRRT) were determined by multivariate analysis, sensitivity analysis, and curve-fitting analysis. RESULTS: A total of 836 cases were included in this study. Multivariate Cox logistic regression analysis showed that SOFA scores were associated with 28- and 90-d mortality in patients with AKI undergoing CRRT. The adjusted HR of SOFA for28-d mortality were 1.18 (1.14, 1.21), 1.24 (1.18, 1.31), and 1.19 (1.13, 1.24) in the three models, respectively, and the adjusted HR of SOFA for 90-d mortality was 1.12 (1.09, 1.16), 1.15 (1.10, 1.19), and 1.15 (1.10, 1.19), respectively. The subgroup analysis showed that the SOFA score was associated with 28-d and 90-d mortality in patients with AKI undergoing CRRT. APACHE-II score was not associated with 28- and 90-d mortality patients with AKI undergoing CRRT. Curve fitting analysis showed that SOFA scores increased had a higher prediction accuracy for 28- and 90-d than APACHE-II. CONCLUSIONS: The SOFA score showed a higher accuracy of mortality prediction in critically ill patients with AKI undergoing CRRT than the APACHE-II score.

A Retrospective Population Study to Develop a Predictive Model of Prediabetes and Incident Type 2 Diabetes Mellitus from a Hospital Database in Japan Between 2004 and 2015.

BACKGROUND Type 2 diabetes mellitus is a global public health problem. Prediabetes may be reversed by weight loss, diet, and lifestyle changes. However, without intervention, between 30-50% of individuals with prediabetes develop type 2 diabetes. This retrospective population study was conducted to develop a predictive model of prediabetes and incident type 2 diabetes mellitus using data from 2004 to 2015 from the DRYAD Japanese hospital database. MATERIAL AND METHODS A retrospective longitudinal population study was conducted using the DRYAD database from Murakami Memorial Hospital, Gifu, Japan, to construct a predictive model for prediabetes and incident type 2 diabetes mellitus in the population. Univariate analysis and multivariate analysis were performed to identify the variables that were associated with prediabetes. These variables were used to construct (75% samples) and verify (25% samples) the predictive model. RESULTS From 2004 to 2015, a total of 11,113 cases were identified. Multivariate logistic regression analysis included the six variables of age, waist circumference, smoking history, the presence of fatty liver, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c) level. Data were used to construct (75% samples) and verify (25% samples) in a predictive model. The area under the receiver operating characteristic (ROC) curve (AUC) of the predictive model was 0.87 (0.85-0.89) in the training cohort and 0.87 (0.86-0.90) in the validation cohort. CONCLUSIONS A prognostic model based on six variables was predictive for incident type 2 diabetes mellitus and prediabetes in a healthy population in Japan.

Higher body mass index is not a protective risk factor for 28-days mortality in critically ill patients with acute kidney injury undergoing continuous renal replacement therapy.

Background: Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is a fatal and common clinical disorder in critically ill patients. Recent studies have shown that the relationship between BMI and the outcome of patients with AKI undergoing CRRT is conflicting. Methods: A retrospective cohort study based on data reuse. Univariate analysis, multi-factor regression analysis and subgroup analyses were used to explore the association of the BMI with the 28-days mortality risk in patients with AKI undergoing CRRT. Results: From January 2009 to September 2016, a total of 1120 cases met the inclusion criteria and were enrolled in this study. The univariate analysis showed that BMI was associated with 28-days mortality of patients with AKI undergoing CRRT, its HR value was 0.98 (0.96, 0.99). The multi-factor regression analysis showed that BMI was not associated with 28-days mortality of patients with AKI undergoing CRRT in the four models, the adjusted HR value of four models were 1.00 (0.96, 1.04), 1.01 (0.97, 1.04), 1.00 (0.96, 1.04) and 1.00 (0.96, 1.04), respectively. The subgroups analyses showed that the BMI was a risk factor of the 28-days mortality in patients with AKI undergoing CRRT when GFR ≥30 mL/min, its HR value was 1.04 (1.01, 1.09). Conclusion: Higher BMI was not a protective risk of 28-day mortality in patients with AKI undergoing CRRT. Especially, when GFR ≥30 mL/min, higher BMI increased the risk of the 28-day mortality rate in patients with AKI undergoing CRRT.

Inflammatory stimuli promote oxidative stress in pancreatic acinar cells via Toll-like receptor 4/nuclear factor-κB pathway.

The Toll­like receptor 4/nuclear factor­κB (TLR4/NF­κB) pathway is vital to the pathogenesis of acute pancreatitis (AP). The aim of the present study was to identify the mechanism of the activation of the TLR4/NF­κB signaling pathway in the viability of primary pancreatic cells. The cells were stimulated with lipopolysaccharide (LPS) for the activation of NF­κB signaling. Next, the reactive oxygen species (ROS) level was evaluated by detecting the concentration of malondialdehyde and glutathione peroxidase. Cell viability was measured by Cell Counting Kit­8 and MTT assays, while the percentage of apoptosis was detected by flow cytometry. Quantitative polymerase chain reaction was used to detect TLR4, B­cell lymphoma 2 (Bcl2), Bcl2­associated X protein (Bax) and phorbol­12­myristate­13­acetate­induced protein 1 (PMAIP1) expression levels. Western blot assay was also conducted to detect TLR4 protein expression, while the activity of NF­κB signaling was measured by determining the p65 and phosphorylated p65 protein levels. In addition, the effect of TLR4 overexpression or treatment with TLR4 antagonists in the presence of LPS stimulation was investigated. The results revealed that ROS levels were increased and cell viability was decreased in LPS­stimulated pancreatic acinar cells. TLR4, Bax and PMAIP1 levels were increased, Bcl2 expression was decreased and NF­κB signaling was activated in LPS­stimulated pancreatic acinar cells. Furthermore, pancreatic cells with TLR4 overexpression exhibited increased ROS level and decreased viability. Finally, the effect caused by LPS stimulation was partially reversed by treatment of pancreatic acinar cells with TLR4 antagonists. In conclusion, the current study investigated a novel regulatory mechanism of the TLR4/NF­κB pathway in LPS­stimulated pancreatic cells, which may contribute to pancreatitis. The damage of these cells due to increased ROS levels was observed to occur through activation of the TLR4/NF­κB pathway.

Augmenter of liver regeneration (ALR) regulates acute pancreatitis via inhibiting HMGB1/TLR4/NF-κB signaling pathway.

This research aimed to explore the effect of augmenter of liver regeneration (ALR) in acute pancreatitis (AP) of mice and the underlying mechanism. Caerulein were given to mice to get AP models. AP mice were given saline, ALR plasmids or negative control plasmids. Then, pancreas tissues were fixed and stained for histological examination. The levels of serum amylase, serum lipase, MPO, HMGB1, TNF-α, IL-1ß as well as MCP-1 were detected by ELISA assay. The mRNA levels of TLR4, p65, IκBα, iNOS, COX-2 and GAPDH were examined by RT-qPCR. The protein levels of HMGB1, TLR4, MD2, MyD88, IκBα and GAPDH were detected by western blotting. ALR decreased serum amylase as well as lipase levels and alleviated the histopathological alterations of the pancreas in AP mice. ALR decreased the MPO activity of pancreas in AP Mice. ALR decreased the HMGB1/TLR4 signaling pathway in AP Mice. ALR decreased pancreas IL-1ß and MCP-1 in AP mice, and also decreased plasma TNF-α and IL-1ß in AP mice. ALR attenuated the cerulein-caused increase in p65 mRNA and protein levels, but had no effects on mRNA and protein levels of IκBα. The AP mice significantly promoted the mRNA levels of iNOS and COX-2 that was inhibited by ALR. HNE formation was also increased in AP mice, but it was decreased by ALR. ALR alleviates acute pancreatitis by inhibiting HMGB1/TLR4/NF-κB signaling pathway. It is promising to alleviate the syndromes of patients with acute via targeting ALR.

miR-135b-5p Promotes migration, invasion and EMT of pancreatic cancer cells by targeting NR3C2.

The exact mechanisms of metastasis for pancreatic cancer remain to be uncovered. This study aimed to elucidate the potential functional mechanism of miR-135b-5p in migration, invasion and epithelial-to-mesenchymal transition (EMT) of pancreatic cancer cells. By real-time PCR and analysis of GEO database, we determined the up-regulated expression of miR-135b-5p in pancreatic cancer tissues and cell lines. Clinically, highly expressed miR-135b-5p was closely related to advanced TNM stage, more lymph node metastasis, more distant metastasis and worse overall survival (OS) and disease-free survival (DFS). Functionally, Transwell assays indicated that miR-135b-5p was a promoter for migration and invasion of pancreatic cancer cells. Additionally, immunohistochemistry staining and Western blot showed that highly expressed miR-135b-5p accelerated EMT process of pancreatic cancer cells. Furthermore, a series of experiments and rescue experiments revealed that Nuclear Receptor Subfamily 3 Group C Member 2 (NR3C2) was the target of miR-135b-5p in pancreatic cancer cells, mediating the promotion effects of miR-135b-5p on the tumor cells migration, invasion and EMT. In conclusion, miR-135b-5p, maybe a novel therapeutic target for pancreatic cancer, promoted migration, invasion and EMT of pancreatic cancer cells by targeting NR3C2.

The Toll-like receptor 4 antagonist TAK-242 protects against chronic pancreatitis in rats.

Chronic pancreatitis is a progressive disease characterized by irreversible morphological changes to the pancreas, typically causing pain and permanent loss of function. It is a poorly understood disease with the pathogenesis remaining unclear. The authors' previous data demonstrated that the inhibition of Toll­like receptor 4 (TLR4) using TLR4 antagonist kinase (TAK)­242 attenuates taurocholate­induced oxidative stress via the regulation of mitochondrial function in the pancreatic acinar cells of mice. In the present study, the effect of TAK­242 on trinitrobenzene sulfonic acid (TNBS)­induced chronic pancreatitis was investigated in rats. The results revealed that TAK­242 attenuated the severity of chronic pancreatic injury, and regulated extracellular matrix secretion and cellular immunity. In addition, TAK­242 treatment significantly decreased cell apoptosis, as evidenced by the reduction in Terminal deoxynucleotidyl transferase dUTP nick end labeling­positive cells in pancreas tissue sections, and also promoted cell proliferation in TNBS­treated animals. Furthermore, the results of the calibrated von Frey filament assay demonstrated that TAK­242 could prevent the pancreatitis­induced referred abdominal hypersensitivity. In summary, TAK­242 exhibits protective effects against TNBS­induced chronic pancreatitis and may be a potential therapeutic strategy for the treatment of patients with chronic pancreatitis.

The toll-like receptor 4 antagonist transforming growth factor-ß-activated kinase(TAK)-242 attenuates taurocholate-induced oxidative stress through regulating mitochondrial function in mice pancreatic acinar cells.

BACKGROUND: Acute pancreatitis (AP) is a commonly occurring and potentially life-threatening disease. Recently, toll-like receptor 4 (TLR4) has been considered as a new clue for studying the pathogenesis of AP due to its important role in inflammatory response cascade. MATERIALS AND METHODS: The aim of this study was to investigate the potential protective effect of transforming growth factor-ß-activated kinase (TAK)-242, a novel TLR4 antagonist, in taurocholate-treated mice pancreatic acinar cells. The protective effects were measured by cell viability, lactate dehydrogenase release and apoptosis, and oxidative stress was assayed by lipid peroxidation and oxidative enzyme activities. To determine the potential underlying mechanisms, mitochondrial cytochrome c release, swelling, and calcium buffering capacity were measured in isolated mitochondria, and mitochondrial biogenesis and expression of mitochondrial dynamic proteins were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Treatment with 6-mM taurocholate significantly increased the expression of TLR4 at both mRNA and protein levels. TAK-242 markedly increased cell viability, decreased lactate dehydrogenase release, and inhibited apoptotic cell death as measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining in pancreatic acinar cells. These protective effects were accompanied by the suppressed lipid peroxidation and enhanced endogenous antioxidative enzyme activity. Using isolated and purified mitochondria from pancreatic acinar cells, we found that TAK-242 treatment also inhibited cytochrome c release into the cytoplasm, mitochondrial swelling, and decrease in mitochondrial Ca2+ buffering capacity after taurocholate exposure. In addition, TAK-242 significantly promoted mitochondrial biogenesis, as evidenced by increased mtDNA and upregulated mitochondrial transcription factors. The results of Western blot analysis showed that TAK-242 also differently regulated the expression of mitochondrial fusion and fission proteins. CONCLUSIONS: All these data strongly indicated that blocking TLR4 activity via TAK-242 exerts protective effects in an in vitro AP model, and it could be a possible strategy to improve clinical outcome in AP patients.

Preoxygenation using invasive ventilator in volume control mode in patients with emergency intubation can shorten the time of preoxygenation and improve the quality of preoxygenation: A retrospective study.

Preoxygenation can rapidly improve oxygenation and enhance the security of endotracheal intubation, so it is very essential before endotracheal intubation. The conventional preoxygenation method self-inflating bag (SIB) is not very effective in case of emergency. So our study aims to find a more effective method of preoxygenation in a critical situation.We retrospectively analyzed data of 105 patients in this study. A total of 49 patients with preoxygenation with invasive ventilator in volume control mode (VCM) and 56 patients with preoxygenation with SIB were included. No significant differences were detected in the baseline data of the 2 groups (P > 0.05). Time of preoxygenation (95%) was 174 (168-180) seconds in group VCM and 205 (199-212) seconds in group SIB (P < 0.05), and multifactor linear regression showed that its main risk factors were the methods of preoxygenation and PO2 before preoxygenation (P < 0.05). Immediate SPO2 after preoxygenation was 91 (89-92)% in group VCM and 85 (83-86)% in group SIB (P < 0.05). Total time of preoxygenation and intubation was 266 (252-280) seconds in group VCM and 318 (298-338) seconds in group SIB (P < 0.05). The 24-hour and overall survival rate in group SIB were lower than in group VCM (P > 0.05). Cox regression showed that SaO2 at 5 minutes after intubation was the major risk factor for the survival rate.Invasive ventilator with volume control mode can shorten the time of preoxygenation and improve the quality of preoxygenation in patients with emergency intubation and may be a better method of preoxygenation in a critical situation.

MicroRNA-153 is a prognostic marker and inhibits cell migration and invasion by targeting SNAI1 in human pancreatic ductal adenocarcinoma.

Human pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with early metastasis, which leads to poor prognosis for patients. Mounting evidence suggests that microRNAs (miRNAs) act as critical factors for tumor recurrence and metastasis. miR-153 has been suggested as a novel tumor-associated miRNA, which is involved in tumor metastasis. However, the clinical significance of miR-153 and its role in PDAC remains to be investigated. The aim of the present study was to investigate the expression levels of miR-153 using RT-qPCR in human PDAC cell lines and tissues. A clinical association analysis was performed to investigate the clinical significance of miR-153. The results showed that, the relative expression of miR-153 in PDAC cells was obviously decreased as compared to that in the normal human pancreatic duct epithelial cell line. The mean expression of miR-153 in PDAC tissues was significantly reduced as compared to that in the normal pancreatic tissues. The clinical analysis revealed that a low expression of miR-153 was closely associated with poor prognostic features and shorter long-term survival of PDAC patients. Furthermore, univariate and multivariate Cox regression analyses showed that miR-153 was an independent prognostic factor for predicting survival in PDAC patients. In vitro studies demonstrated that the upregulation of miR-153 inhibited migration and invasion in MIAPaCa-2 cells. By contrast, the downregulation of miR-153 increased the number of migrated and invaded AsPC-1 cells. miR-153 inversely regulated SNAI1 abundance in MIAPaCa-2 cells. Notably, SNAI1 was identified as a direct target of miR-153 in PDAC. Furthermore, an inverse correlation between miR-153 and SNAI1 expression was observed in PDAC tissues. In conclusion, the results showed miR-153 is an independent prognostic marker for predicting survival in PDAC patients and inhibits cell migration and invasion by targeting SNAI1.

[Down-expression of FOXA2 in gastric adenocarcinoma].

OBJECTIVE: To investigate the expression of FOXA2 in human gastric adenocarcinoma and its correlation with cell migration and invasion. METHODS: Fifty-six pairs of gastric adenocarcinoma and matched tumor-adjacent tissues were freshly collected. The expressions of FOXA2 and epithelial cadherin (E-cadherin) in the gastric specimens were detected using immunohistochemistry. Western blotting was performed to test FOXA2 and E-cadherin expressions in different gastric cancer cell lines. FOXA2 was over-expressed in MKN-45 cells. TranswellTM assays were performed to observe gastric cancer cell migration and invasion in vitro. Spearman rank correlation coefficient was used for correlation analysis. RESULTS: The expressions of FOXA2 and E-cadherin in gastric adenocarcinoma were significantly lower than those in matched tumor-adjacent noncancerous tissues. FOXA2 was positively correlated with E-cadherin expression in gastric adenocarcinoma tissues. Clinical analysis suggested that FOXA2 expression was prominently associated with tumor differentiation, infiltration depth, lymph node metastasis and TNM stage, respectively. The lowest expressions of FOXA2 and E-cadherin were found in highly invasive gastric cancer MKN-45 cell line; the highest expressions of FOXA2 and E-cadherin were observed in low metastatic gastric cancer N-87 cell line. Over-expression of FOXA2 significantly increased the expression of E-cadherin protein and obviously inhibited cell migration and invasion in MKN-45 cells. CONCLUSION: Expression of FOXA2 is reduced in gastric adenocarcinoma tissues and its low-expression is correlated with malignant clinical pathological features. Over-expression of FOXA2 in MKN-45 cells up-regulates E-cadherin expression and inhibits gastric cancer cell migration and invasion.