[Research advances of myeloid-derived suppressor cells mediated by programmed death-1/programmed death-ligand 1 pathway in sepsis-induced immunosuppression].

Sepsis is a life-threatening organ dysfunction due to dysregulation of the body's response to infection. The immunosuppressive phase of sepsis is also an important cause of high morbidity and mortality in patients with advanced sepsis. Myeloid-derived suppressor cell (MDSC), as a heterogeneous population of Gr1+CD11b+ immature cells, play a pivotal role in the immune process of advanced sepsis together with programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) with immunosuppressive properties. This review summarized the research progress of PD-1/PD-L1 pathway-mediated mechanism of MDSC in septic immunosuppression in recent years. The mechanism of action of PD-1/PD-L1 pathway in the immunosuppressive stage, the effects of PD-1/PD-L1 pathway on the "dual-signaling" model of MDSC through the signaling pathway and cytokines, as well as the time course of PD-1/PD-L1 pathway mediation in sepsis were described.

Classification of nasal polyps and inverted papillomas using CT-based radiomics.

OBJECTIVES: Nasal polyp (NP) and inverted papilloma (IP) are two common types of nasal masses. And their differentiation is essential for determining optimal surgical strategies and predicting outcomes. Thus, we aimed to develop several radiomic models to differentiate them based on computed tomography (CT)-extracted radiomic features. METHODS: A total of 296 patients with nasal polyps or papillomas were enrolled in our study. Radiomics features were extracted from non-contrast CT images. For feature selection, three methods including Boruta, random forest, and correlation coefficient were used. We choose three models, namely SVM, naive Bayes, and XGBoost, to perform binary classification on the selected features. And the data was validated with tenfold cross-validation. Then, the performance was assessed by receiver operator characteristic (ROC) curve and related parameters. RESULTS: In this study, the performance ability of the models was in the following order: XGBoost > SVM > Naive Bayes. And the XGBoost model showed excellent AUC performance at 0.922, 0.9078, 0.9184, and 0.9141 under four conditions (no feature selection, Boruta, random forest, and correlation coefficient). CONCLUSIONS: We demonstrated that CT-based radiomics plays a crucial role in distinguishing IP from NP. It can provide added diagnostic value by distinguishing benign nasal lesions and reducing the need for invasive diagnostic procedures and may play a vital role in guiding personalized treatment strategies and developing optimal therapies. CRITICAL RELEVANCE STATEMENT: Based on the extraction of radiomic features of tumor regions from non-contrast CT, optimized by radiomics to achieve non-invasive classification of IP and NP which provide support for respective therapy of IP and NP. KEY POINTS: • CT images are commonly used to diagnose IP and NP. • Radiomics excels in feature extraction and analysis. • CT-based radiomics can be applied to distinguish IP from NP. • Use multiple feature selection methods and classifier models. • Derived from real clinical cases with abundant data.

[Assessment of research efficiency of critical care medicine in hospitals affiliated S university based on data envelopment method: taking the 13th Five-Year Plan period as an example].

OBJECTIVE: To investigate the static and dynamic trends of scientific research efficiency of the critical care medicine in hospitals affiliated S university during the 13th Five-Year Plan period. METHODS: Based on the scientific research data of 16 hospitals affiliated to Beijing S University from 2014 to 2020, the scientific research investment funds and the number of physicians involved in scientific research were selected as input evaluation indexes, and the number of science citation index (SCI) papers, Chinese science citation database (CSCD) papers, and the number of masters and doctors trained were selected as output evaluation indexes, and the evaluation index system of scientific research efficiency of critical care medicine was constructed. SPSS version 23.0 software was used for descriptive data statistics, and data envelopment analysis (DEA)-BCC model and DEA-Malmquist index model of DEAP 2.1 software were used for static and dynamic evaluation of its scientific research efficiency from 2016 to 2020, respectively. RESULTS: (1) The scientific research technical efficiency (TE) of critical care medicine in 16 hospitals affiliated with S universities varied greatly from 2016 to 2020, but pure technical efficiency (PTE) and scale efficiency (SE) were at a good level, and 6-11 affiliated hospitals in critical care medicine kept DEA effective for 5 consecutive years. (2) Dynamic analysis of their total factor productivity (TFP) of scientific research from 2016 to 2020 showed a trend of rising and then falling and then rising again. The mean value was 0.985. The technical efficiency change (TEC) showed a decreasing and then increasing trend, and the technical progress change (TC) showed a slow increasing and then decreasing trend, with a mean value of 0.953. While the mean values of TEC, pure technical efficiency change (PTEC) and scale efficiency change (SEC) were above 1, which showed that the growth of total factor productivity index of research and innovation depended more on the technical efficiency index. CONCLUSIONS: The "gain effect" and "catch-up effect" of scientific research efficiency in the specialty of critical care medicine in hospitals affiliated S universities are obvious, but the "growth effect" is not obvious. "Although the research efficiency of the 13th Five-Year Plan period has been significantly improved, there is still much room for improvement in scientific and technological innovation and international academic influence.

A comparative study of olanzapine, aripiprazole and risperidone in the treatment of psychiatric and behavioral symptoms of Alzheimer's disease.

To investigate the efficacy and safety of olanzapine, aripiprazole, and risperidone in the treatment of mental and behavioral symptoms of Alzheimer's Disease. A retrospective analysis was performed on the clinical data of 126 patients with Alzheimer's Disease from February 2018 to February 2020. The patients were divided into group A (aripiprazole, n=44), group B (olanzapine, n=42) and group C (risperidone, n=40) based on the treatment method. Remarkably differences at different time points among the three groups were observed (P<0.05). Significant differences in the Positive and Negative Syndrome Scale scores of different time points and cross-group comparison among the three groups were detected (P<0.05). The time-point comparison of BEHAVE-AD scores among the three groups indicated a remarkable difference (P<0.05). After 4 weeks of treatment, the Positive and Negative Syndrome Scale and BEHAVE-AD scores of group A were lower than those of groups B and C (P<0.05). The total incidence of adverse reactions in group A was remarkably lower than in groups B and C (P<0.05). Olanzapine, aripiprazole and risperidone are effective in treating Alzheimer's disease and aripiprazole, with a better safety profile and fewer adverse reactions, is more suitable for elderly patients.

Effect of dexmedetomidine on opioid consumption and pain control after laparoscopic cholecystectomy: a meta-analysis of randomized controlled trials.

INTRODUCTION: The clinical evidence on dexmedetomidine (DEX) for postoperative pain scores and opioid consumption remains unclear in laparoscopic cholecystectomy (LC). AIM: To evaluate whether DEX could reduce opioid consumption and pain control after LC. MATERIAL AND METHODS: A meta-analysis search of EMBASE, PubMed and Cochrane CENTRAL databases was performed and randomized controlled trials (RCTs) comparing DEX with control for adult patients undergoing LC were searched. The primary outcome was opioid consumption in the first 24 h after the operation. The secondary outcomes were the time of first request of analgesia, visual analogue scale (VAS) scores 24 h after the operation, the incidence of patients' need for rescue analgesics, opioid-related adverse effects, DEX-related adverse effects and other complications. RESULTS: There were fourteen aspects of twelve trials and 967 patients included in the analysis. DEX use significantly reduced the opioid consumption in the first 24 h after the operation (weighted mean difference (WMD), -19.17; 95% confidence interval (CI), -30.29 to -8.04; p = 0.0007), lengthened the time of first request of analgesia (WMD = 38.90; 95% CI: 0.88-76.93; p = 0.04) and lowered post-operative nausea or vomiting (PONV) (odds ratio (OR) = 0.49; 95% CI: 0.27-0.89; p = 0.02). CONCLUSIONS: Intravenous DEX infusion significantly improved the duration of the analgesic effect and reduced postoperative opioid consumption. Moreover, lower incidence of post-operative nausea or vomiting was found in the DEX group.

Quercetin inhibits caerulein-induced acute pancreatitis through regulating miR-216b by targeting MAP2K6 and NEAT1.

Acute pancreatitis (AP) is a common acute abdominal disease with high mortality and mortality rates. Increasing evidences clarified that Traditional Chinese Medicine (TCM) adjuvant therapy for AP can be used and it gives a positive effect. Quercetin (3,3',4',5,7-pentahydroxyflavone, QE) is a type of flavone compound with positive effect on cancer and inflammation prevention. The current study aims to identify the effect of QE on AP and potential molecular effect. In this case, caerulein (CAE) induced AP cell and mice model were used. QE alleviated inflammatory mediators TNF-α, IL-6, and IL-10 in experiments. In addition, miR-216b was increased based on QE treatment. In further study, MAP2K6 of p38/MAPK signaling pathway was identified as a direct target of miR-216b, and QE inhibited p38/MAPK signaling pathway through up-regulating miR-216b. Our study also first confirmed that long non-coding RNA NEAT1 is a direct target of miR-216b and can be suppressed by QE. Because of the target, NEAT1, miR-216b, and MAP2K6 formed a competitive endogenous RNA (ceRNA) network. Besides direct target mediated by QE, it also decreased TNF-α which down-regulated TRAF2 and MAP3K5 located on upstream of p38/MAPK signaling and formed a feedback loop. In conclusion, QE has a protective effect on AP through inhibiting p38/MAPK signaling pathway by up-regulating miR-216b and suppressing TNF-α.

Baicalin Protects Against Acute Pancreatitis Involving JNK Signaling Pathway via Regulating miR-15a.

Acute pancreatitis (AP) is a kind of reversible inflammatory process of the exocrine pancreas. During the process, systemic inflammatory syndromes are involved, which relates closely to inflammatory mediators. Baicalin is a type of flavone compound extracted from Scutellaria baicalensis Georgi and exhibits anti-inflammation effect in several cancers. In this study, baicalin displayed a suppressing role on IL-1[Formula: see text], TNF[Formula: see text] and IL-6 in both cell and mice models. Necrosis was decreased in the baicalin treatment group and got a markedly lower pathological score. In this study, miR-15a is the core intermediate in baicalin regulation, which increased through baicalin treatment and protected pancreas cells and tissues, inhibiting the JNK signaling pathway by targeting MAP2K4. The long non-coding RNA MALAT1 is also a direct target of miR-15a and forms a competitive endogenous RNA (ceRNA) network with MAP2K4, which can be regulated by baicalin. In addition, upstream genes, including CDC42 and MAP3K1, were also regulated by baicalin, of which CDC42 was confirmed to form the second ceRNA network with MALAT1 and miR-15a. In conclusion, baicalin exhibits therapeutic activity towards AP by pumping up miR-15a level and inhibiting CDC42/MAP3K1, which affects AP as a brake by targeting MAP2K4 and inhibiting the JNK signaling pathway.

High-density lipoprotein cholesterol as a factor affecting virus clearance in covid-19 patients.

OBJECTIVE: There were COVID-19 patients with SARS-COV-2 nucleic acid long-term positive. This article aims to understand the relevant factors that affect SARS-COV-2 clearance time. METHODS: The clinical data of 115 COVID-19 patients with SARS-COV-2 nucleic acid positive time exceeding 14 days were collected retrospectively, and the relationship between clinical characteristics, chest CT scans, blood cells, biochemical indicators, and the time of viral nucleic acid turning negative were analyzed. RESULTS: The time from symptom onsets to nucleic acid turning negative was (32.5 ± 8.7) days in this group of patients. The time of nucleic acid turning negative: no fever group was longer than fever group, diabetes group was longer than no comorbidity group, elevated levels of ALT (alanine aminotransferase), or GLU (fasting blood glucose) group, decreased levels of ALB (albumin) group or HDLC (high-density lipoprotein cholesterol) group was longer than it's normal group separately (P < 0.05). Cox multivariate regression analysis showed that ALT [odds ratio (OR): 2.164 (95% CI: 1.276-3.670), P = 0.004], GLU [OR: 2.064 (95% CI: 1.195-3.566), P = 0.009] and HDLC [OR: 0.527 (95% CI: 0.307-0.907), P = 0.021] were independent factors which affected the time of nucleic acid turning negative. CONCLUSIONS: ALT, GLU and HDLC were independent factors that influenced the time of nucleic acid turning negative. Although diabetes or hyperglycemia is a known risk factor, HDLC is the first to be identified, clinicians should be aware of dyslipidemia in covid-19 patients.

[Design of a support bracket to facilitate prone ventilation in critically ill patients].

Acute respiratory distress syndrome (ARDS) is an important cause of death in critically ill patients. Prone ventilation is one of the effective treatment methods for ARDS, but the current clinical implementation rate is not high, which is mainly due to the occurrence of serious complications such as tracheal tube and venous pipeline disconnection, pressure sores, hemodynamic instability and so on, and requires adequate personal and cooperation. The medical staff of the department of critical care medicine of Beijing Shijitan Hospital Affiliated to Capital Medical University designed a kind of support bracket for human body carrying and turning over which can help the critically ill patients to easily complete the position conversion during prone position ventilation, and has obtained the national utility model patent (Patent Number: ZL 2017 2 1847759.9). The support bracket is simple in design, composed of stent, rotating shaft and bandage. It is reliable and easy to operate. It can significantly reduce the difficulty of prone position ventilation, avoid the occurrence of related complications, reduce the labor load of medical staff, and improve the treatment quality of patients.

Higher maternal embryonic leucine zipper kinase mRNA expression level is a poor prognostic factor in non-small-cell lung carcinoma patients.

Aim: To elucidate potential prognostic significance of MELK mRNA expression in non-small-cell lung carcinoma patients. Methods: A loop algorithm based on R software was used to select genes with the best prognostic value. Mantel-Haenszel method and functional enrichment analysis were used to perform this analysis. Results:MELK mRNA expression level in tumor tissue is significantly higher than that in normal/benign tissue (p < 0.001), and gradually increases from stage I to IV (lung adenocarcinoma: p = 0.011; lung squamous cell carcinoma: p = 0.002), and is negatively correlated with prognosis in lung adenocarcinoma patients (HR: 2.025 in univariate analysis; HR: 2.162 in multivariate analysis). However, it does not show a significant correlation in lung squamous cell carcinoma patients. Conclusion:MELK is a poor biomarker for non-small-cell lung carcinoma patients and can potentially be used as a therapeutic target.

[Validation of a septic myocardial inhibition model by intraperitoneal injection of endotoxin in rats].

OBJECTIVE: To establish septic myocardial inhibition rat model by echocardiography. METHODS: Twenty adult male Sprague-Dawley (SD) rats were divided into control group and model group according to the random number table method, with 10 rats in each group. The rat model of septic myocardial inhibition was reproduced by intraperitoneal injection of 10 mg/kg lipopolysaccharide, while the control group was given the same volume of saline. The left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic diameter (LVDs), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), right ventricular end-diastolic diameter (RVDd), right ventricular end-systolic diameter (RVDs), heart rate (HR), positive pulmonary artery flow rate and aortic flow rate were measured at 8 hours after model establishment by echocardiography. Then the rats were sacrificed to harvest serum and myocardial tissue. The levels of serum tumor necrosis factor-α (TNF-α), nuclear factor-ΚB (NF-ΚB), interleukin-1 (IL-1), cardiac troponin I (cTnI) and B-type brain natriuretic peptide (BNP) were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of TNF-α, IL-1 and NF-ΚB in myocardium were detected by real-time polymerase chain reaction (real-time PCR). The pathological changes of myocardium were observed by hematoxylin-eosin (HE) staining under light microscope. RESULTS: Compared with control group, myocardial inhibition was obviously observed in model group, manifesting as enlargement of overall shape of heart, and prominent increase of HR (bpm: 449.0±21.1 vs. 356.7±23.3, P < 0.01); left ventricular and right ventricular functions were affected, LVDd, LVDs, LVEDV, LVESV were enlarged [LVDd (mm): 10.03±0.95 vs. 7.04±0.71, LVDs (mm): 5.95±0.71 vs. 3.07±0.05, LVEDV (mL): 2.11±0.53 vs. 0.81±0.21, LVESV (mL): 0.51±0.16 vs. 0.07±0.01, all P < 0.05], LVEF was significantly decreased (0.760±0.046 vs. 0.901±0.025, P < 0.01), RVDd was significantly increased (mm: 4.48±0.58 vs. 3.22±0.20, P < 0.05), and positive pulmonary artery velocity was significantly decreased (cm/s: 64.2±9.3 vs. 89.0±0.8, P < 0.05). Compared with control group, the levels of serum NF-ΚB, TNF-α, IL-1, BNP and cTnI in model group were significantly increased [NF-ΚB (ng/L): 103.84±6.55 vs. 57.29±41.34, TNF-α (ng/L): 1 198.32±164.07 vs. 835.45±24.01, IL-1 (ng/L): 1 089.90±221.96 vs. 746.19±165.83, BNP (ng/L): 1 097.36±293.84 vs. 454.71±197.79, cTnI (ng/L): 6 938.59±1 400.21 vs. 3 731.90±1 349.31, all P < 0.01], the mRNA expressions of TNF-α, NF-ΚB and IL-1 in myocardial tissue were significantly increased (2-ΔΔCT: 1.50±0.42 vs. 0.71±0.40, 1.10±0.17 vs. 0.63±0.06, 1.77±0.67 vs. 0.10±0.03, all P < 0.05). It was shown by HE staining that the structure of myocardial tissue in control group was distinct, the arrangement of myocardial fibers was neat, and transverse was clear; the structure of myocardial tissue in model group was loose, blurred, and the cells were swollen, with obvious pathological changes. CONCLUSIONS: Cardiac function was assessed by echocardiography, expression of inflammatory factors, myocardial markers and pathological changes. It was verified that intraperitoneal injection of 10 mg/kg endotoxin could successfully prepare a rat model of septic myocardial inhibition.

A negative Smad2/miR-9/ANO1 regulatory loop is responsible for LPS-induced sepsis.

The roles of miR-9 in tumor progression are well-defined, however, its roles and the mechanisms in sepsis are still unclear. This work aims to explore miR-9 roles and related mechanism in LPS-induced sepsis. We found that miR-9 level was significantly upregulated in septic patients and RAW264.7 cells with LPS treatment, knockdown of miR-9 attenuated the induced effects of LPS on IL-6 and TNF-α secretion. In vivo experiments showed that miR-9 expression was increased in septic mice and knockdown of miR-9 partially reversed the upregulation of IL-6 and TNF-α levels in septic mice and prolonged the survival of septic mice. Mechanistic studies revealed that miR-9 could target ANO1, which inactivates the TGF-ß/Smad2 signaling. Conversely, Smad2 could bind to the promoter of miR-9 and promote miR-9 expression. Notably, ANO1 overexpression or Smad2 knockdown attenuated miR-9 knockdown-mediated inhibition on LPS-induced sepsis. Therefore, these results suggest that the negative Smad2/miR-9/ANO1 regulatory loop is responsible for LPS-induced sepsis.

OCT4B-190 protects against ischemic stroke by modulating GSK-3ß/HDAC6.

OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B and OCT4B1. The 190-amino-acid protein isoform (OCT4B-190) is one of the major products of OCT4B mRNA, the biological function of which is still not well defined. Recent evidence suggests that OCT4B-190 may function in the cellular stress response. The glycogen synthase kinase-3ß (GSK-3ß) and histone deacetylase 6 (HDAC6) are also key stress modulators that play critical roles in the ischemic cascades of stroke. Hence, we here further investigated the effects of OCT4B-190 in the experimental stroke, and explored the underlying roles of GSK-3ß and HDAC6. We found that OCT4B-190 overexpression enhanced neuronal viability at 24 h after oxygen-glucose deprivation (OGD) treatment. Moreover, in male C57BL/6 mice subjected to transit middle cerebral artery occlusion (MCAO), OCT4B-190 overexpression reduced infarct volume and improved neurological function after stroke. Notably, we found spatio-temporal alterations of GSK-3ß and HDAC6 in the ischemic cortex and striatum, which were affected by adenovirus-mediated OCT4B-190 overexpression. OCT4B-190 demonstrated similar impacts on neuronal cultures in vitro, downregulating OGD-induced GSK-3ß activity and HDAC6 expression. In addition, we found that GSK-3ß and HDAC6 were co-expressed in the cytoplasm of neurons, and OCT4B-190 had an effect on interactions between GSK-3ß and HDAC6 in neuronal cultures subjected to OGD treatment. These findings suggest that OCT4B-190 exerts neuroprotection in the experimental stroke potentially by regulating actions of GSK-3ß and HDAC6 simultaneously, which may be an attractive therapeutic strategy for ischemic stroke.

Effect of interleukin-31 on septic shock through regulating inflammasomes and interleukin-1ß.

Sepsis with severe systemic inflammation remains a great challenge for the intensive care unit in clinics. Although biomarkers have been identified to diagnose, monitor and predict these syndromes, novel therapeutic approaches are required for the amelioration of symptoms of sepsis and septic shock. The present study demonstrated that interleukin (IL)-31 was able reduce the mortality rate of lipopolysaccharide (LPS)-induced sepsis with the reduction of inflammatory cytokines in the sera. IL-31 also inhibited IL-1ß production in the peritoneal lavage fluid in LPS-induced or cecal ligation and puncture-induced sepsis. The in vitro mechanism responsible for IL-31 regulation on peritoneal IL-1ß activation following LPS challenge was explored. It was demonstrated that IL-1ß secretion was suppressed by IL-31 treatment from LPS-challenged peritoneal macrophages following adenosine triphosphate stimulation, which is an activator of NLR family, pyrin domain-containing 3 (NLRP3). Furthermore, IL-31 inhibited the expression of NLRP3 at the transcriptional level. In human THP-1 cells, anti-IL-31/anti-IL-31 receptor (R) neutralizing antibody enhanced NLRP3 expression as well as IL-1ß activation, suggesting a role of the IL-31-IL-31R-NLRP3-IL-1ß signaling axis in the physiological status of sepsis. On the other hand, IL-31 displayed a negative effect on the NLRP1 inflammasome, but not on NLRP3 on the LPS-primed human peripheral blood monocytes, resulting in reduction of the inflammatory cytokine, tumor necrosis factor (TNF)-α, in the supernatant. Taken together, the present data implied that T helper 2-type cytokine, IL-31, may be a promising therapeutic option for treatment of sepsis and septic shock in clinics.

[Predictive value of early phrase echocardiography and cardiac biological markers in patients with severe sepsis: a five-year single-center retrospective study].

OBJECTIVE: To assess the predictive value of early phrase echocardiography and cardiac biomarkers in patients with severe sepsis. METHODS: A retrospective analysis of severe septic patients (patients with acute coronary syndrome and end stage renal disease were excluded) in department of intensive care unit of Capital Medical University Affiliated Beijing Shijitan Hospital from January 2013 to December 2017 was conducted. The acute physiology and chronic health evaluation II (APACHE II) score, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI), myoglobin (MYO), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) within 6 hours after admission, and bedside echocardiography indexes [left ventricular ejection fraction (LVEF), the ratio of the peak blood flow velocity in the early stage of the mitral valve and the peak blood flow rate of the mitral valve (E/A ratio)] within 6 hours after diagnosis were recorded. The differences of indexes between patients with decreased contractile function (LVEF < 0.50) group and normal group, and the difference between dead group and survival group within 28-day were compared. Receiver operating characteristic (ROC) curve and Logistic regression analysis were conducted to assess the early detected prognostic value in severe sepsis patients. RESULTS: (1) A total of 316 patients were enrolled in the survey period. Decreased cardiac systolic function (LVEF < 0.50) was found in 89 cases (28.2%), and cardiac diastolic function impaired (E/A ratio < 1) in 269 cases (85.1%); while 79 cases (25.0%) had both systolic function and diastolic function impairment. (2) NT-proBNP and cTnI were statistically different between cardiac systolic function impaired group and normal group. Further Logistic regression analysis showed that only NT-proBNP was significantly correlated with LVEF [ß=-1.311, odds ratio (OR) = 0.269, P < 0.001]. (3) Eighty-two of 316 cases were died in 28-day, and the 28-day mortality rate was 25.9%. Compared with the survival group, the ratio of E/A < 1, APACHE II score, NT-proBNP, cTnI, MYO, CK and CK-MB were significantly increased in death group. The ROC curve analysis showed that the above indexes had diagnosed value for prognosis in severe sepsis patient, among which NT-proBNP and cTnI had higher predictive value [the area under ROC curve (AUC) were 0.920 and 0.901 respectively, both P < 0.001]. Multivariate Logistic regression analysis showed that APACHE II score (ß= 0.282, OR = 1.326, P < 0.001) and NT-proBNP (ß= 0.402, OR = 1.261, P < 0.001) were independent risk factors for prognosis in patients with severe sepsis. CONCLUSIONS: The LVEF values measured by echocardiography in early phrase were unrelated to 28-day prognosis. APACHE II score, E/A ratio, NT-proBNP, cTnI, MYO, CK and CK-MB were related to 28-day prognosis. APACHE II scores and NT-proBNP were independent prognostic factors in severe sepsis patient.

Dexmedetomidine improves the outcomes in paediatric cardiac surgery: a meta-analysis of randomized controlled trials.

OBJECTIVES: Dexmedetomidine has been shown to decrease cardiac complications in adults undergoing cardiac surgery. Results from clinical trials of dexmedetomidine on outcomes following paediatric cardiac surgery are controversial. METHODS: We searched EMBASE, PubMed and Cochrane CENTRAL databases for randomized controlled trials comparing the effect of dexmedetomidine versus placebo or other anaesthetic drugs in paediatric patients undergoing cardiac surgery. The primary outcome was the duration of mechanical ventilation. The secondary outcomes were intensive care unit stay, hospital length of stay (LOS), incidence of junctional ectopic tachycardia and postoperative deaths. RESULTS: Nine trials with a total of 837 patients were selected. Compared with controls, dexmedetomidine significantly reduced the postoperative duration of mechanical ventilation [in hours; n = 837; weighted mean difference -2.20, 95% confidence interval (CI) -3.51 to -0.90; P = 0.001; I2 = 97%], intensive care unit LOS (in days; n = 737; weighted mean difference -0.47, 95% CI -0.90 to -0.03; P = 0.03; I2 = 97%) and hospital LOS (in days; n = 291; weighted mean difference -1.80, 95% CI -3.36 to -0.25; P = 0.02; I2 = 96%). Dexmedetomidine also significantly reduced the incidence of postoperative junctional ectopic tachycardia (21/292 vs 50/263; risk ratio 0.40, 95% CI 0.25-0.64; P = 0.0001; I2 = 0.0%), but there was no difference between groups in postoperative deaths (4/182 vs 6/153; odds ratio 0.54, 95% CI 0.15-1.93; P = 0.34; I2 = 0.0%). CONCLUSIONS: Perioperative administration of dexmedetomidine to paediatric patients undergoing cardiac surgery may shorten the duration of mechanical ventilation, LOS in the intensive care unit and in the hospital and reduce the incidence of junctional ectopic tachycardia. More high-quality randomized controlled trials are encouraged to verify the beneficial effect of dexmedetomidine before its clinical application in paediatric patients undergoing surgery for congenital heart disease.

Application of dead space fraction to titrate optimal positive end-expiratory pressure in an ARDS swine model.

This study aimed to apply the dead space fraction [ratio of dead space to tidal volume (VD/VT)] to titrate the optimal positive end-expiratory pressure (PEEP) in a swine model of acute respiratory distress syndrome (ARDS). Twelve swine models of ARDS were constructed. A lung recruitment maneuver was then conducted and the PEEP was set at 20 cm H2O. The PEEP was reduced by 2 cm H2O every 10 min until 0 cm H2O was reached, and VD/VT was measured after each decrement step. VD/VT was measured using single-breath analysis of CO2, and calculated from arterial CO2 partial pressure (PaCO2) and mixed expired CO2 (PeCO2) using the following formula: VD/VT = (PaCO2 - PeCO2)/PaCO2. The optimal PEEP was identified by the lowest VD/VT method. Respiration and hemodynamic parameters were recorded during the periods of pre-injury and injury, and at 4 and 2 cm H2O below and above the optimal PEEP (Po). The optimal PEEP in this study was found to be 13.25±1.36 cm H2O. During the Po period, VD/VT decreased to a lower value (0.44±0.08) compared with that during the injury period (0.68±0.10) (P<0.05), while the intrapulmonary shunt fraction reached its lowest value. In addition, a significant change of dynamic tidal respiratory compliance and oxygenation index was induced by PEEP titration. These results indicate that minimal VD/VT can be used for PEEP titration in ARDS.

miR-375 ameliorates sepsis by downregulating miR-21 level via inhibiting JAK2-STAT3 signaling.

Accumulating evidences have confirmed that miRNAs have important roles in sepsis. Myeloid-derived suppressor cells (MDSCs) enhance late sepsis development through immunosuppression in mice. Here, the functions and mechanisms of miR-375 in sepsis were revealed. We found that miR-375 level was downregulated but miR-21 level was upregulated in sepsis patients and that their levels were correlated negatively. Importantly, ectopic expression of miR-375 could decrease the number of sepsis Gr1+CD11b+ MDSCs in mice. Mechanistically, miR-375 could target Janus kinase 2 (JAK2) and further impaired signal transducer and activator of transcription 3 (STAT3) in sepsis Gr1+CD11b+ MDSC. Gain and loss of function of experiments showed that upregulation or downregulation of miR-375 level could decrease or increase miR-21 level. Moreover, pretreatment of JAK2 overexpressing vector could abolish the effects of miR-375 on miR-21 level and the amount of sepsis Gr1+CD11b+ MDSCs. Therefore, our results demonstrate that miR-375 could block JAK2-STAT3 pathway and thus modulate miR-21 level, which is involved in regulation of late sepsis.

MiR-21 and MiR-155 promote non-small cell lung cancer progression by downregulating SOCS1, SOCS6, and PTEN.

Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1, SOCS6, and PTEN. Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC.